The different receptor species of liver have similar complex insulin binding properties.
Liver plasma membranes bind insulin in a complex fashion via three prominent disulfide-linked insulin receptor structures of 360K, 300K, and 260K molecular weight. To determine if the complex binding is explained by different binding affinities among the different structures, 125I-insulin was specifically cross-linked to the binding sites and the amount of radiolabeled insulin was determined after SDS-gel electrophoresis. The insulin binding characteristics of each structure were similar to the binding properties of the intact membrane. The Scatchard plot for each structure was curvilinear and the Kd values for the high and low affinity components were similar to the membrane values. Thus, the curvilinear Scatchard plot of insulin binding to liver membranes is also a feature of each receptor structure and is not a function of different receptors with different binding properties.


Effects of intergenerational contact on social capital in community-dwelling adults aged 25-84 years: a non-randomized community-based intervention.
Accumulating social capital in urban areas is essential to improve community health. Previous studies suggested that intergenerational contact may be effective for enhancing social capital. However, no study has examined the effect of intergenerational contact on social capital through a population-based evaluation. This study aimed to investigate the effects of a community-based intervention to increase the frequency of intergenerational contact on social capital among adults aged 25-84 years. This study used a non-randomized controlled trial design to conduct a community-based intervention (from March 2016 to March 2019). The study area was Tama ward, Kawasaki city, Kanagawa, Japan. The area comprises five districts; one district was assigned as the intervention group and the other four districts as the control group. We provided the intervention to residents in the intervention group. The intervention comprised three phases: Phase 1 was the preparation term (organizing the project committee); Phase 2 was the implementation term (trained volunteer staff members, conducted the intergenerational greeting campaign, and held intergenerational contact events); and Phase 3 was the transition term (surrendering the lead role of the project to the city hall field workers). In the control group, field workers provided public health services as usual. We conducted mail surveys in September 2016 and November 2018 to assess the effects of the intervention on social capital during Phase 2. Eligible participants were randomly selected from community-dwelling adults aged 25-84 years according to age (10,620 control group individuals and 4479 intervention group individuals). We evaluated social trust, norm of reciprocity, and social support as outcome variables. In total, 2518 participants completed both surveys and were analyzed (control group: 1727; intervention group: 791). We found that social trust (coefficient = 0.065; 95% confidence interval [CI]: 0.006, 0.125) and norm of reciprocity (coefficient = 0.084; 95% CI: 0.020, 0.149) positively changed in the intervention group compared with the control group. This community-based intervention may contribute to sustaining and improving social capital among community-dwelling adults. UMIN000046769 (UMIN-CTR); first registered on January 28, 2022 (retrospectively registered).


Colovenous fistula complicating diverticulitis. Demonstration by contrast enema.
Colonic diverticulitis is frequently complicated by bowel obstruction, abscess, perforation and fistula formation. We report a unique case of colonic diverticulitis complicated by colovenous fistulization with Gastrografin enema examination demonstrating thrombus in the inferior mesenteric vein.


Identifying Women's Strengths for Promoting Resilience After Experiencing Intimate Partner Violence.
Guided by the Resilience Portfolio Model, this study examined strengths associated with well-being and post-traumatic growth (PTG) among women who had experienced intimate partner violence (IPV). Participants were 109 Spanish women who were receiving specialized psychological services for IPV. They completed a survey on multiple indicators of strengths, subjective well-being, and PTG. The results indicated that PTG was positively correlated with well-being and all strengths. Univariate analysis comparing levels of PTG showed significant differences in all factors, except emotional regulation and optimism. Post hoc analyses revealed two patterns, with some strengths distinguishing across all levels of PTG, and others only discriminating the most resilient women (as indicated by PTG) from the rest. Multivariate analyses accounted for 42% of the variance in posttraumatic growth and 52% in well-being. The results suggest ways to promote well-being and resilience among victimized women.


Comparative effects of magnetic and water-based hyperthermia treatments on human osteosarcoma cells.
Hyperthermia (HT) based on magnetic nanoparticles (MNPs) represents a promising approach to induce the apoptosis/necrosis of tumor cells through the heat generated by MNPs submitted to alternating magnetic fields. However, the effects of temperature distribution on the cancer cells' viability as well as heat resistance of various tumor cell types warrant further investigation. In this work, the effects induced by magnetic hyperthermia (MHT) and conventional water-based hyperthermia (WHT) on the viability of human osteosarcoma cells at different temperatures (37°C-47°C) was comparatively investigated. Fe-Cr-Nb-B magnetic nanoparticles were submitted either to alternating magnetic fields or to infrared radiation generated by a water-heated incubator. In terms of cell viability, significant differences could be observed after applying the two HT treatment methods. At about equal equilibrium temperatures, MHT was on average 16% more efficient in inducing cytotoxicity effects compared to WHT, as assessed by MTT cytotoxicity assay. We propose the phenomena can be explained by the significantly higher cytotoxic effects initiated during MHT treatment in the vicinity of the heat-generating MNPs compared to the effects triggered by the homogeneously distributed temperature during WHT. These in vitro results confirm other previous findings regarding the superior efficiency of MHT over WHT and explain the cytotoxicity differences observed between the two antitumor HT methods.


Kinetics of sickle hemoglobin polymerization. III. Nucleation rates determined from stochastic fluctuations in polymerization progress curves.
The polymerization kinetics of sickle cell hemoglobin are found to exhibit stochastic variations when observed in very small volumes (approximately 10(-10) cm3). The distribution of progress curves has been measured at several temperatures for a 4.50 mM-hemoglobin S sample using a laser-photolysis, light-scattering technique. The progress curves at a given temperature are superimposable when translated along the time axis, showing that the variability of the kinetic progress curves results primarily from fluctuations in the time at which polymerization is initiated. The shapes of the initial part of the progress curves are well-fitted using the functional form I(t) = Io + As exp (Bt), derived from a dual nucleation model. When the distribution of the measured tenth times is broad, the rate of homogeneous nucleation can be obtained by fitting the exponential tail of the distribution. As the distribution sharpen, the rate of homogeneous nucleation can be estimated by modelling the width of the distribution function using a simple Monte-Carlo simulation of the polymerization kinetics. Using the rates of homogeneous nucleation obtained from the distributions, the rates of heterogeneous nucleation and polymer growth can be obtained from the experimental parameters As and B. The resulting nucleation rates are roughly 1000 times greater than those obtained from an analysis of bulk kinetic data. The results provide strong support for the dual-nucleation mechanism and show that the distribution of progress curves provides a powerful independent method for measuring the rate of homogeneous nucleation and thereby obtaining values for the other principal rates of the mechanism.


Use of an optical sensor to directly monitor the metabolic activity of growing bacteria.
The metabolic activity of growing bacteria was directly monitored by using an electro-optical (EO) sensor. The sensor enables examination of bacteria in batch and continuous cultures. As examples, we report studies with Еscherichia coli, a bacterium with an aerobic type of metabolism, and Lactobacillus plantarum, a bacterium with an anaerobic type of metabolism. Bacterial growth was accompanied by a simultaneous change in both the hydrodynamic mean size (HMS) of the bacteria and the concentration of ions in the cytoplasm (CIC). Both variables were associated with the regulation of cellular metabolic activity, which can be cyclic during intense bacterial growth. A simultaneous change in metabolic activity and osmotic regulation was also found. For СIC and HMS measurements, we used online results of the EO analysis of cells suspended in water. The measured results for the CIC and HMS can be used to directly monitor bacterial metabolism. The results of this study are of practical importance for the real-time EO monitoring of the metabolic activity of growing bacteria without preliminary sample preparation.


Comparison of the image quality and radiation dose of different scanning modes in head-neck CT angiography.
To analyze and compare the radiation dose and image quality of different CT scanning modes on head-neck CT angiography. A total of 180 patients were divided into Group A and Group B. The groups were further subdivided according to different scanning modes: subgroups A1, A2, A3, B1, B2, and B3. Subgroups A1 and B1 used conventional CT protocol, subgroups A2 and B2 used the kV-Assist scan mode, and subgroups A3 and B3 used the dual-energy gemstone spectral imaging protocol. The CT dose index and dose-length product were recorded. The objective image quality and subjective image evaluation was conducted by two independent radiologists. The signal-to-noise ratios, contrast-to-noise ratios, and subjective scores of subgroups A3 and B3 were higher than the other subgroups. In subgroups B1 and B2, the subjective scores of 9 patients and 12 patients were lower than 3, respectively. The subjective scores of subgroups B1 and B2 were lower than the other subgroups. There was no statistically significant difference in signal-to-noise ratios, contrast-to-noise ratios, and subjective scores between subgroups A1 and A2. The effective dose of subgroup A2 was 41.7 and 36.4% lower than that in subgroups A1 and A3, respectively (p < 0.05). In Group B, there were no statistically significant differences in CT dose indexvol, dose-length product, and ED among the subgroups (p > 0.05). In the head-neck CT angiography, the kV-Assist scan mode is recommended for patients with body mass index between 18.5 and 34.9 kg m-2; gemstone spectral imaging scanning mode is recommended for patients with body mass index ≥34.9 kg m-2.


Interactions of Nonsteroidal Antiinflammatory Drugs and Aspirin and Risk of Cardiovascular Disease in Patients With Osteoarthritis.
Nonsteroidal antiinf lammatory drugs (NSAIDs) remain the mainstay of the pharmacologic management for relieving osteoarthritis pain, and low-dose aspirin is often prescribed to osteoarthritis patients who are at high risk of cardiovascular disease (CVD). We conducted cohort studies using data from The Health Improvement Network (THIN) database (2000-2019) to assess whether the relationship of initiation of naproxen or ibuprofen vs. initiation of other NSAIDs (excluding both naproxen and ibuprofen), respectively, to the risk of CVD was modified by coprescription of low-dose aspirin among the participants with osteoarthritis. Among participants without coprescription of aspirin, the risk of CVD was lower in naproxen initiators (10.3/1000 person-years) than in other NSAIDs initiators (13.2/1000 person-years; hazard ratio = 0.71, 95% confidence interval: 0.60, 0.85). Among participants with coprescription of aspirin, however, the risk of CVD was higher among naproxen initiators (36.9/1000 person-years) than that among other NSAIDs initiators (34.8/1000 person-years; hazard ratio = 1.48, 95% confidence interval: 1.12, 1.84). The association was significantly modified by coprescription of aspirin (P < 0.001). Similar findings were observed in the association of initiation of ibuprofen vs. other NSAIDs with the risk of CVD, which was significantly modified by coprescription of aspirin (P < 0.001). These findings suggest that osteoarthritis patients and clinicians should be aware of the potential CVD risk of concurrently taking naproxen or ibuprofen and low-dose aspirin.


Methyl tertiary-butyl ether inhibits THP-1 macrophage cholesterol efflux in vitro and accelerates atherosclerosis in ApoE-deficient mice in vivo.
The biosafety of methyl tertiary-butyl ether (MTBE), mainly used as a gasoline additive, has long been a contentious topic. In addition to its routine toxicities, MTBE has been demonstrated to disrupt glucose and lipid metabolism and contribute to the development of type 2 diabetes as well as obesity. As one of the morbidities related to dyslipidemia, atherosclerosis is worthy of being investigated under MTBE exposure. Since foam cells derived from macrophages play pivotal roles during atherosclerosis development, we studied the effects of MTBE on macrophages in vitro and assessed the effect of MTBE on atherosclerosis plaque formation with the ApoE-/- mouse model in vivo for the first time. Our results demonstrated that exposure to MTBE at environmentally relevant concentrations decreased the expression of ABCA1 and ABCG1, which are responsible for macrophage cholesterol efflux, at both mRNA and protein levels in THP-1 macrophages. Consequently, treatment with MTBE inhibited the transport of cholesterol from macrophages to High-density lipoprotein. ApoE-/- mice exposed to MTBE at environmentally relevant concentrations (100, 1000 μg/kg) displayed significant increases in lesion area in the aorta and aortic root compared to vehicle-treated ones. Further analysis indicated that MTBE exposure enhanced the macrophage-specific marker Mac-2 contents within plaques in the aortic root, implying that MTBE could promote macrophage-derived foam cell formation and thus accelerate atherosclerosis plaque formation. We for the first time demonstrated the pro-atherogenic effect of MTBE via eliciting disruption of macrophage cholesterol efflux and accelerating foam cell formation and atherosclerosis plaque development.


[Cytogenetic characterization of Solanum lycopersicoides Dun. alien chromosome additions in cultivated tomato].
Cytogenetic analysis of five Solanum lycopersicoides monosomic alien addition lines of tomato was carried out. Meiotic analysis showed that additional chromosomes caused serious abnormalities. It was demonstrated that different chromosomes of S. lycopersicoides had different effects on chromosome pairing. For instance, associations formed between chromosomes II and IV of S. lycopersicoides and chromosomes of cultured tomato were trivalents, while chromosome XI in all cells was present as a univalent. Pachytene analysis showed that chromosomes of homeologous group II paired at their long arms, and their nucleolus organizer regions were of different sizes. The use of molecular markers provided accelerated identification of the introgression of S. lyvcopersicoides genetic material.


Is antegrade endopyelotomy really less invasive than open pyeloplasty?
We investigated the invasiveness of antegrade endopyelotomy and open pyeloplasty in two consecutive series of patients with ureteropelvic junction obstruction. 98 patients were treated by open pyeloplasty from 1980 to 1991, and 137 patients by antegrade endopyelotomy from 1991 to 1999. Diagnosis of ureteropelvic junction obstruction was made by excretory urogram and/or antegrade pyelography, diuretic renography and retrograde pyelography. Invasiveness was evaluated by the postoperative need for analgesics, the complication rate and the residual long-term symptoms after surgery. The postoperative need for opiate analgesics was significantly higher in patients after open pyeloplasty than after antegrade endopyelotomy. Ten percent of the patients complained of problems with the lumbotomy scar after open pyeloplasty, which was not encountered after endopyelotomy. Complications after open pyeloplasty occurred in 24% and were more severe than the 11% seen after endopyelotomy. The primary success rate after open pyeloplasty was 98 and 89% after antegrade endopyelotomy. The long-term success rate, > or = 24 month postoperatively, was 96% (median follow-up 37 (24-196) months) and 76% (median follow-up 32 (24-73) months), respectively. Open pyeloplasty and endopyelotomy both have a high success rate with better patency results after open pyeloplasty. Open pyeloplasty is more invasive and has a higher morbidity. Endopyelotomy is a minimally invasive procedure with faster recovery, fewer and minor complications, significantly less need for peri- and postoperative analgesics, less residual pain due to the access, and no functional and esthetic sequelae of lumbotomy.


Concise solid-phase synthesis enables derivatisation of YEATS domain cyclopeptide inhibitors for improved cellular uptake.
YEATS domains, which are newly identified epigenetic readers of histone lysine acetylation and crotonylation, have emerged as promising anti-cancer drug targets. We recently developed AF9 YEATS domain-selective cyclopeptide inhibitors. However, the cumbersome and time-consuming synthesis of the cyclopeptides limited further structural derivatisation and applications. Here, we reported a concise method for the solid-phase synthesis of the cyclopeptides, which substantially reduced the amount of time required for the preparation of the cyclopeptides and led to a higher overall yield. Moreover, this new synthetic route also allowed further derivatisation of the cyclopeptides with various functional modules, including fluorescent dye and cell-penetrating peptide. We demonstrated that the conjugation of the cyclopeptide with cell-penetrating peptide TAT led to a significantly increased cellular uptake.


'Locked-in syndrome' for 27 years following a viral illness: clinical and pathologic findings.
We describe a man who, after a presumed encephalitic illness, was "locked-in" for 27 years. His CT and autopsy findings showed atrophy of the brainstem and a cystic lesion at the base of the pons. He survived longer than most other patients in a similar state.


Electro-acupuncture for post-stroke cognitive impairment: A protocol for systematic review and meta-analysis.
A considerable number of stroke survivors suffered from cognitive impairment, and more than one third of stroke survivors are affected at 3 and 12 months after the stroke. Although the published systematic reviews suggest that acupuncture can help improve post-stroke cognitive dysfunction, the power of the results is low due to study limitations. Therefore, this review is necessary to analyze the effect of acupuncture on cognitive impairment after stroke and to provide evidence for cognitive impairment in stroke. This study will be carried out in strict accordance with the Cochrane Handbook for Systematic Reviews of Interventions. According to the pre-established search strategy (PICOS framework), all the literature will be obtained from online databases including Cochrane Central Register of Controlled Trials in the Cochrane Library, Medline (via PubMed), EMBASE (via embase.com), CINAHL (via EBSCOhost), China National Knowledge Infrastructure database, WanFang Database, Chinese Science and Technology Periodical Database, and Sino-Med Database from inception until December 31, 2021 with no language limitations. Two reviewers will screen the records and include quality studies according to inclusion criteria independently. The data needed will be extracted independently by 2 authors according to a table of data extraction. Any inconsistencies in literature screening and data collection will be resolved to reach a consensus via discussion with a third author. Risk of bias for each study will be assessed using risk of bias tool. RevMan5.3 will be used to analyze the data. Heterogeneity will be identified and measured by Chi2. Subgroup analyses and sensitivity analysis will be carried out. Grading of Recommendations Assessment, Development and Evaluation will be used to evaluate the evidence for each outcome. The results of this study will provide a theoretical basis for the clinical use of electro-acupuncture to treat cognitive dysfunction after stroke. INPLASY202210038.


[Effect of nematoda Aphanitylenchus sp. on the reproductive capacity of fleas Ceratophyllus consimilis].
The paper presents results of experimental studies of the effect of Allantonematidae on the reproduction of fleas. It has been established that the pairing of non-infected females with males infected with nematodes reduces the fecundity rate while the pairing of non-infected males with females infected with nematodes causes a complete stopping of reproduction of laboratory population. The conclusion was drawn on the role of allantonematides in the regulation of abundance of fleas of rodents in nature.


A phase I study of bevacizumab (B) in combination with everolimus (E) and erlotinib (E) in advanced cancer (BEE).
VEGF, mTOR, and EGFR inhibitors have demonstrated anti-tumor and anti-angiogenic effects alone and in combination with each other. This study evaluated the safety, tolerability, and pharmacokinetics of bevacizumab, everolimus, and erlotinib combination. Doublet therapy consisted of bevacizumab at 10 mg/kg every 14 days and everolimus 5 mg daily which escalated to 10 mg daily. Erlotinib 75 mg daily was added to the phase II dose recommended phase II dose (RPTD) of bevacizumab and everolimus. Dose-limiting toxicity (DLT) was assessed in cycle 1. Forty-eight patients with advanced solid malignancies were evaluable for DLT and efficacy. No DLTs were observed in the doublet dose escalation. Two DLTs (grade 3 mucositis and grade 3 rash) were observed with the addition of erlotinib 75 mg daily. Consequently, triplet doses were adjusted and were better tolerated. Four patients had a partial response. Median progression-free survival (PFS) for the doublet therapy was 6.0 months (0.5 to 32+ months) and 5.5 months (0.8 to 27+ months) for the triplet therapy. Systemic exposure of everolimus was significantly higher in combination with erlotinib (476 ± 161 ng h/mL) compared to when given alone (393 ± 156 ng h/mL; P = 0.020). The RPTD for the doublet therapy is bevacizumab 10 mg/kg every 14 days and everolimus 10 mg daily, and the RPTD for the triplet therapy is bevacizumab 5 mg/kg every 14 days, everolimus 5 mg and erlotinib 75 mg daily. Prolonged disease stability was demonstrated in tumors known to respond to mTOR inhibition and potentially resistant to VEGF blockade.


The long-term persistence of tumor necrosis factor inhibitors in patients with moderate to severe immune-mediated rheumatic diseases: A nation-wide, population-based real-world study.
We aimed to compare the long-term persistence between different tumor necrosis factor-alpha inhibitors (TNFis) with immune-mediated rheumatic diseases (IMRD). This study can potentially provide insights into the real-world evidence regarding safety and effectiveness of TNFi treatment in a Chinese population. We enrolled newly diagnosed IMRD patients in this active comparator, retrospective cohort study by using National Taiwan insurance claim datasets. The drug survivals of first-line TNFi agents, including etanercept, golimumab, and adalimumab were compared. Propensity score matching was conducted to control the confounding effect from the observed covariates. The cumulative proportion of discontinuation was calculated over 5 years. The multiple-variable regression and propensity score analysis was used for confounding adjustment. After propensity score matching, there were 2267 patients identified in each etanercept, golimumab, and adalimumab group. We observed the 5-year cumulative proportion of discontinuation was 52.80%, 45.85%, and 56.86% in etanercept, golimumab, and adalimumab, respectively. Compared with golimumab, increase of 31% (95% CI: 20-43) and 38% (95% CI: 26-50) risk of discontinuation were observed in etanercept and adalimumab. The factors including female gender, increasing age, long hospital stays, without co-medication with nonsteroidal anti-inflammatory drugs or methotrexate were associated were discontinuation of first-line TNFi treatment. Golimumab had better drug survival than etanercept or adalimumab over 5 years of observation in Asian IMRD patients. Gender, age, longer hospital stays, concomitant use of disease-modifying antirheumatic drugs were associated with survival with TNFis.


Long-term survival in 618 patients from the Western Washington Streptokinase in Myocardial Infarction trials.
The aim of this study was to determine whether streptokinase treatment improves long-term survival in patients with acute myocardial infarction. Thrombolytic treatment for acute myocardial infarction reduces early mortality and improves the 1-year survival rate, but the long-term (3 to 8 years) survival benefits of treatment and the relation between survival and baseline clinical characteristics, infarct size and ventricular function have not been established. We assessed survival status at a minimum of 3 and a mean of 4.9 +/- 2.3 years in 618 patients randomized between 1981 and 1986 to receive conventional treatment (n = 293) or thrombolysis with streptokinase (n = 325) in the Western Washington Intracoronary (n = 250) and Intravenous (n = 368) Streptokinase in Myocardial Infarction trials. The relation between long-term survival and thrombolytic treatment, admission baseline clinical characteristics and late radionuclide tomographic thallium-201 infarct size and ejection fraction was assessed in a subset of patients. Survival at 6 weeks was 94% in patients who received streptokinase versus 88% in the control group (p = 0.01). However, survival at 3 years was 84% in the streptokinase group and 82% in the control group and for the total period of follow-up, there was no significant survival benefit (p = 0.16). Analysis by infarct location showed a higher survival rate at 3 years for patients treated with anterior infarction (76% vs. 67% for the control group), but no overall survival benefit (p = 0.14). Survival at 3 years for patients with an inferior infarction was 89% in the streptokinase group and 91% in the control group (p = 0.62). By stepwise Cox regression analysis, admission clinical variables associated with decreased long-term survival were anterior infarction, advanced age, history of prior infarction and the presence of pulmonary edema or hypotension. Although streptokinase therapy was associated with improved survival, it was not an independent determinant of survival (p = 0.069). Ejection fraction and thallium-201 infarct size measured approximately 8 weeks after enrollment had a strong association with long-term survival. Univariate analysis in a subgroup of 289 patients with complete data selected infarct size, ejection fraction, age and history of prior infarction as predictors of survival. In the multivariate model, only ejection fraction (p < 0.0001), age (p = 0.008) and prior myocardial infarction (p = 0.02) remained strong predictors. In these early trials of thrombolytic therapy for acute myocardial infarction, streptokinase improved early survival, but there was little long-term survival benefit. This failure to show an improvement in the 3- to 8-year survival rate may also reflect the need to study a larger group of patients or to initiate treatment earlier after symptom onset.


[Analysis on the causes and prevention strategies of the vascular injury caused by the oblique lateral lumbar fusion].
To analyze the causes of vascular injury occurred in oblique lateral interbody fusion for treating lumbar degenerative diseases, and put forward preventive measures. There were 235 patients analyzed from October 2014 to May 2017 in five hospitals, who were treated with oblique lateral interbody fusion with or without posterior pedicle screw fixation. There were 79 males and 156 females with an average age of (61.9±13.5) years old (ranged from 32 to 83 years). There were 7 cases of vascular injury, including 4 cases of segmental vessel injury, 1 case of left common iliac artery injury, 1 case of left common iliac veininjury and 1 case of ovarian vein injury. The follow up time ranged from 6 to 36 months, averagely (15.6±7.5) months. There was no pedicle screw loosen or fracture. The low back pain VAS decreased from preoperative 6.7±2.3 to 1.4±0.8 at the latest follow-up, which was statistically difference(t=7.21, P=0.033). The ODI decreased from preoperative (36.5±7.7)% to (9.4±3.6)% at the latest follow-up, which was statistically difference (t=8.11, P=0.025). Oblique lateral interbody fusion technique provides a new method for minimally invasive fusion of lumbar internal fixation. However, it has a risk of vascular injury. In order to effectively prevent the occurrence of vascular injury, the operative indications and careful and meticulous operation should be strictly grasped.


Clinical Presentations and Semen Characteristics of Men Attending the Secondary Referral Infertility Clinic at Mumbai, India.
Limited information is available on the aetiology and semen profiles of male infertility in Indian population. The aim of this study is to study the clinical and semen characteristics of men attending the infertility clinic and also to understand the impact of World Health Organization (WHO) 2010 reference values on the diagnosis of male infertility. A retrospective study evaluating the medical case records (January 2005 to December 2015, [n = 1906]) of men attending infertility clinic in Mumbai, India. The aetiology was classified based on the andrology evaluation and other investigations. Semen profiles were compared during the years 2005-2010 and 2011-2015 using WHO 1999 and WHO 2010 criteria, respectively. The Chi-square and Mann-Whitney U tests were performed using Open Source Epidemiological software and Social science calculators. The aetiology of male infertility was determined in 62% of the men; while the cause remained undetermined in 38%. Varicocele (25%), urogenital infections (10%), sexual dysfunctions (8%) and vas aplasia (8%) were identified as major aetiologies in our cohort. Men with sexual dysfunctions and vas aplasia were significantly higher during the years 2011-2015 as compared to 2005-2010. Men having normozoospermia (10%) and azoospermia (3%) were increased, whereas those having oligoasthenozoospermia (17%) were reduced in 2011-2015 as compared to 2005-2010. According to WHO 1999 criteria , 12-15% of men showed abnormal semen profiles. The semen parameters of these men became normal on using WHO 2010 reference values. Varicocele is the most common aetiology in infertile men. Idiopathic infertility was seen in a higher proportion among the infertile men.


NO-induced activation of cyclic GMP-dependent pathway down regulates ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) protein in rat C6 glioma.
In rat C6 glioma cells, the ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (NPP1), a modulator of purinergic receptor signaling, is down regulated after an increase in intracellular cAMP by addition of dibutyryl cAMP, a membrane-permeable cAMP-analog, or by activation of the β-adrenoceptor receptor with (-)-isoproterenol (Aerts et al., 2011, Eur. J. Pharmacol. 654, 1-9). In this communication we studied the effect of nitric oxide (NO)/cGMP, a pathway also affecting purinergic receptor signaling, on the level of NPP1 protein. Sodium nitroprusside (SNP), a NO donor, reduces NPP1 protein in a dose-dependent manner. A combination of SNP and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, an inhibitor of soluble guanylate cyclase, demonstrated that NO-dependent down regulation of NPP1 was caused by NO-sensitive guanylyl cyclase. Treatment with Rp-pCPT-cGMPS, an inhibitor of protein kinase G (PKG), showed that PKG is not involved in the down regulation of NPP1. In addition, we have shown that the cAMP- and cGMP-dependent decrease in NPP1 expression is unrelated. These results indicate that NO/cGMP regulates the level of NPP1 protein by a pathway that differs from the cAMP-induced decrease in NPP1.


Scientific appraisal of Unani concept of islah-e-advia (rectification/purification of drugs) and its importance.
Unani system of medicine uses drugs from plants, minerals and animals (Mawaleed-e-salasa) origin. Most of the drugs used are believed to be safe, but some drugs may have toxins and produce harmful effects, so it is very important to remove the toxins or to minimize their harmful effects before using, so as to increase their therapeutic values and make easy for use. To explore the concept, aims and objectives of islah-e-advia (rectification/purification of drugs) in Unani system of medicine. A through literature survey was undertaken using the various online bibliographic databases like Pub Med, Google Scholar, Science Direct, Web of Science and Scopus. Classical Unani literature books which are translated in Urdu by CCRUM were used for Unani references. The keywords used for the search included "Tadbeer-e-Advia", "Islah-e-advia", Mudabbar process, detoxification and purification of drug. The ancient Unani physicians were well aware of toxicity of the drugs and have divided drugs into four degrees (1°, 2°, 3° and 4°) according to the Mizaj (temperament) of drugs. The fourth degree drugs produce so strong effects that the physiological functions of the body get disturbed; such drugs are also considered to be poisonous drugs. Different methods of purification have been mentioned for drugs belonging to the third and fourth degree temperament and always recommended their use after subjecting them to certain Tadbeer (rectification/purification). Otherwise these drugs may destroy the physiological function of the body. After purification process the drugs become physically and chemically pure, therapeutically more effective and less toxic. Very few pharmacological and toxicity studies have been conducted. Third and fourth degree drugs and its formulations have been claimed by Unani scholars to be useful in the management of various diseases of the body. After purification toxicity has been reduced in comparison crude drug. However, further elaborate and comprehensive studies are required to validate such claims.


Alkyl-methylimidazolium ionic liquids affect the growth and fermentative metabolism of Clostridium sp.
In this study, the effect of ionic liquids, 1-ethyl-3-methylimidazolium acetate [EMIM][Ac], 1-ethyl-3-methylimidazolium diethylphosphate [EMIM][DEP], and 1-methyl-3-methylimidazolium dimethylphosphate [MMIM][DMP] on the growth and glucose fermentation of Clostridium sp. was investigated. Among the three ionic liquids tested, [MMIM][DMP] was found to be least toxic. Growth of Clostridium sp. was not inhibited up to 2.5, 4 and 4 g L(-1) of [EMIM][Ac], [EMIM][DEP] and [MMIM][DMP], respectively. [EMIM][Ac] at <2.5 g L(-1), showed hormetic effect and stimulated the growth and fermentation by modulating medium pH. Total organic acid production increased in the presence of 2.5 and 2 g L(-1) of [EMIM][Ac] and [MMIM][DMP]. Ionic liquids had no significant influence on alcohol production at <2.5 g L(-1). Total gas production was affected by ILs at ≥ 2.5 g L(-1) and varied with type of methylimidazolium IL. Overall, the results show that the growth and fermentative metabolism of Clostridium sp. is not impacted by ILs at concentrations below 2.5 g L(-1).


Skeletal and blood biochemical characteristics of sheep during growth and breeding: a comparison of flocks with and without broken mouth.
Two-hundred female Scottish Blackface sheep ranging in age from 3 months to 5 1/2 years were used to investigate the relationships between blood biochemical characteristics, skeletal metabolism and dental health on 5 farms, 3 with broken mouth and 2 with no incidence of the disease. Skeletal growth to 6 months of age was faster in lambs from control flocks than in lambs from affected farms although growth thereafter was slower in the control group. A generally lower protein intake on control farms may account for this reduced growth rate. In general, adult dimensions of bones were attained between 14 and 30 months of age but age of maturation varied between bones; tibial endochondral growth ended after 14 to 21 months while the rib still showed evidence of endochondral growth at 70 months of age. This growth was episodic, being maximal during lactation and possible causes are discussed. There was no significant differences in calcium or phosphorus status between control and affected populations, an inadequate phosphorus intake during pregnancy was common to both groups. Lower serum magnesium concentration in affected than in control sheep was a consistent finding and is discussed.


Phylogenetic clusters of rhizobia revealed by genome structures.
Rhizobia, bacteria that fix atmospheric nitrogen, are important agricultural resources. In order to establish the evolutionary relationships among rhizobia isolated from different geographic regions and different plant hosts for systematic studies, we evaluated the use of physical structure of the rhizobial genomes as a phylogenetic marker to categorize these bacteria. In this work, we analyzed the features of genome structures of 64 rhizobial strains. These rhizobial strains were divided into 21 phylogenetic clusters according to the features of genome structures evaluated by the endonuclease I-CeuI. These clusters were supported by 16S rRNA comparisons and genomic sequences of four rhizobial strains, but they are largely different from those based on the current taxonomic scheme (except 16S rRNA).


Identification of nuclear factor IV/Ku autoantigen in a human 2D-gel protein database. Modification of the large subunit depends on cellular proliferation.
Nuclear Factor IV (NFIV) is a heterodimeric DNA-binding protein from HeLa cells, recognizing molecular ends and is identical to the autoantigenic target Ku. We have identified the two NFIV/Ku subunits, by comigration, in the 2D-gel database of transformed human amnion cell (AMA) proteins. We observed that the large subunit of NFIV/Ku consists of at least 3 charge variants that correspond to SSP IEFs 5705 (81.2 kDa, pI 5.74), 6707 (81.2 kDa, pI 5.67) and 6706 (81.9 kDa, pI 5.60) in the AMA catalogue. The relative amounts of the 2 major variants (IEFs 5705 and 6707) was dependent on the state of cell proliferation. Inhibition of DNA-synthesis by hydroxyurea also changed the relative levels of the variants, whereas aphidicolin or a thymidine block had no effect. These results suggest a possible role for NFIV/Ku in DNA replication.


Venous thromboembolism and radiation therapy: The final radiation-induced thrombosis study analysis.
Thromboembolic events frequently complicate the course of malignancy and represent a major cause of morbidity and mortality in cancer patients. In contrast to chemotherapy and other systemic therapies, little is known about the impact of ionizing radiations on the incidence of venous thromboembolism (VTE) in cancer patients. In the present prospective study, we aimed to investigate the incidence, management, and outcome of VTE in newly diagnosed cancer patients who received curative radiotherapy. VTE was found in 8 patients, out of 401 patients at a median time of 80 days after radiotherapy initiation. The incidence rate of VTE at 6 months post-treatment was 2% (95% CI, 0.9-3.7), with 50% of cases occurring during the radiotherapy course and 50% of cases in patients who received or were receiving chemotherapy. As none of the patients harbored a personal history of VTE, no prophylactic measure was initiated during cancer therapy. Most patients received monotherapy with low-molecular-weight heparin and were still on surveillance at the end of the study. No specific clinical risk factor was identified that might systematically indicate the need of thromboprophylaxis in the context of curative radiotherapy. Although this pan-cancer descriptive study did not relate an increased risk of short-term thrombosis following ionizing radiation, it provides important insight as a basis for future studies with subcategories of cancer, in order to in fine guide further recommendations in frail patients. NCT02696447.


Two sessions of sleep-focused mind-body bridging improve self-reported symptoms of sleep and PTSD in veterans: A pilot randomized controlled trial.
Sleep disturbance is highly prevalent among veterans. As an alternative to sleep medications with their undesirable side effects, nonpharmacological mind-body interventions may be beneficial for sleep management in primary care. The aim of this pilot study was to investigate whether a novel mind-body intervention, mind-body bridging (MBB), focusing on sleep, could improve self-reported sleep disturbance and comorbid symptoms in veterans. This pilot study was a randomized controlled trial at the Veterans Affairs Salt Lake City Health Care System in which 63 veterans with self-reported sleep disturbance received MBB or an active sleep education control. Both interventions were conducted in two sessions, once per week. Patient-reported outcomes included the following: primary-Medical Outcomes Study (MOS) Sleep Survey, MOS Short Form-36V; secondary-Center for Epidemiological Studies-Depression, PTSD Check List-Military, Five-Factor Mindfulness Questionnaire. At both Week 1 (1 week after the first session) and post-intervention assessments, while sleep disturbance decreased in both groups, MBB performed significantly better than did the control group. Furthermore, self-reported PTSD symptoms improved in MBB, while they remained unchanged in the control. Overall mindfulness increased in MBB, while it remained unchanged in the control. This study provides preliminary evidence that a brief sleep-focused MBB could be a promising intervention for sleep and potentially other comorbid symptoms (e.g., PTSD). MBB could help patients develop awareness skills to deal with sleep-related symptoms. Integration of MBB into primary care settings may enhance care of patients with sleep disturbance and co-morbid symptoms.


The application of 3D bioprinting in urological diseases.
Urologic diseases are commonly diagnosed health problems affecting people around the world. More than 26 million people suffer from urologic diseases and the annual expenditure was more than 11 billion US dollars. The urologic cancers, like bladder cancer, prostate cancer and kidney cancer are always the leading causes of death worldwide, which account for approximately 22% and 10% of the new cancer cases and death, respectively. Organ transplantation is one of the major clinical treatments for urological diseases like end-stage renal disease and urethral stricture, albeit strongly limited by the availability of matching donor organs. Tissue engineering has been recognized as a highly promising strategy to solve the problems of organ donor shortage by the fabrication of artificial organs/tissue. This includes the prospective technology of three-dimensional (3D) bioprinting, which has been adapted to various cell types and biomaterials to replicate the heterogeneity of urological organs for the investigation of organ transplantation and disease progression. This review discusses various types of 3D bioprinting methodologies and commonly used biomaterials for urological diseases. The literature shows that advances in this field toward the development of functional urological organs or disease models have progressively increased. Although numerous challenges still need to be tackled, like the technical difficulties of replicating the heterogeneity of urologic organs and the limited biomaterial choices to recapitulate the complicated extracellular matrix components, it has been proved by numerous studies that 3D bioprinting has the potential to fabricate functional urological organs for clinical transplantation and in vitro disease models.


Religion and addiction.
Religion with its rituals can become an object of addiction, especially when a child while growing up experiences neglect and abuse. It is also very common that such individuals transfer their feelings of anger, rage and sometimes even true hatred to God. Then God becomes the substitute for their displaced vengeance (upon those who abused them as children).


Ultrastructural studies of cerebral vascular spasm after cardiac arrest-related global cerebral ischemia in rats.
The present investigation was undertaken to study the ultrastructural morphology of brain blood vessels during vasospasm following total cerebral ischemia. Global cerebral ischemia was produced in rats by compression of the cardiac vessel bundle (i.e., cardiac arrest) using a metal hook that was introduced into the mediastinum. Ischemia lasted for 10 min with blood recirculation for 6, 12 and 24 h. Rat brains were perfusion-fixed and regions from the cerebral cortex and associated leptomeningeal vessels were evaluated by scanning and transmission electron microscopy. We noted three general vasoconstrictive responses in vessels of various sizes including veins and arteries. These alterations related to the smooth muscle cell arrangement associated with each constricted vessel including a circumferential, and longitudinal arrangement, or a combination of both types. Other features in the three types of vasoconstricted vessels included thickening of the vessel basement membranes with increased endothelial microfilaments and vesicular profiles. Our studies present evidence that ischemia of 10-min duration with blood reflow for 6, 12 and 24 h produces profound and variable vasospastic changes in some but not all vessels. These vascular alterations are thought to be caused in part by vasoactive substances released both by endothelial and blood cells and by perivascular cellular elements in response to the ischemic episode.


Development and results of a Case Coordination Activity Tracking tool.
This study describes the development of a tool used to track the who, what, when, and how much of case coordination for elderly, community-based clients. The Case Coordination Activity Tracking Form measures phase of coordination (assessment, plan development, plan implementation, monitoring reassessient, and discharge), type of activity (in-person, telephone, documentation, research, travel, case conference), with whom contact took place (client, family, client/family together, supervisor/colleague, service provider, physician, program access committee), and special circumstances (e.g., infection control). Over a 6-month span, we used the tool to study case coordination of services for elderly, community-based clients. The average amount of coordination time was 5.15 hours (n = 234), with 71% of the clients requiring between 2 and 6hours of coordination, and 26% of the clients accounting for 49% of the total coordination time. Frequency and average amount of coordination declined greatly after the first month. Not all clients required coordination each month, and monitoring was the most common activity in later months. The tool was found to be reliable and easy to use, and of benefit to decision makers, managers, and case coordinators in measuring, analyzing, and describing case coordination. This tool could be readily used with other client groups.


Fate of exogenous hyaluronic acid in the middle ear.
The fate of exogenous high-molecular-weight hyaluronic acid applied in the middle ear was studied in rats. Tritium-labelled hyaluronic acid was deposited, and its disappearance through the eustachian tube was followed by analysis of nasopharyngeal secretions. Radioactivity in the secretions reached a peak after three hours and approached zero after 12 hours, indicating that almost all hyaluronic acid had been removed. The middle ears were all empty when opened 24 hours after the deposition of hyaluronic acid. The fate of hyaluronic acid after obstruction of the eustachian tube was followed both with radioactive hyaluronic acid and subsequent autoradiography and by direct analysis of the hyaluronic acid concentration and the hyaluronic acid molecular weight distribution. Radioactive hyaluronic acid was confined to the obstructed middle ear, and no uptake into surrounding tissues could be detected between three hours and four days after the deposition. The amount of hyaluronic acid deposited could be recovered to about the same extent for up to six days. Analysis of the molecular weight distribution of the deposited material indicated only a slow degradation, if any, during the same time period.


Locomotor impairment and cerebrocortical oxidative stress in portal vein ligated rats in vivo.
Oxidative/nitrosative stress plays an important role in the pathogenesis of hepatic encephalopathy and ammonia toxicity. The present study was undertaken in order to investigate the impact of portal vein ligation on cerebrocortical oxidative stress and its relation to locomotor activity. Cerebral protein tyrosine nitration, RNA oxidation, locomotor activity, and microglia activation were studied in rats that underwent portal vein ligation (PVL). Two weeks after PVL, increased levels of protein tyrosine nitration and RNA oxidation were found in the brain. PVL rats exhibited hyperammonemia and reduced locomotor behaviour, but displayed no signs of microglia activation or upregulation of the mRNAs for interleukin-1ß and tumor necrosis factor-α. PVL also had no effect on astrocytic glutamate transporter or inducible nitric-oxide synthase expression. Only cerebral Il-6 mRNA levels were increased. Daily administration of indomethacin prevented PVL-induced protein tyrosine nitration, RNA oxidation, Il-6 mRNA increase, and the impairment of locomotor activity, but did not prevent PVL-induced hyperammonemia. The data suggest that PVL triggers oxidative/nitrosative stress in the brain without activation of microglia and neuroinflammation. Prevention of protein tyrosine nitration and RNA oxidation by indomethacin also prevents the disturbances in locomotor activity pointing to a relevance of oxidative stress in the pathophysiology of HE.


The Impact of Histologic Subtype on Receipt of Adjuvant Chemotherapy and Overall Survival in Stage III Colon Cancer: a Retrospective Cohort Analysis.
The impact of adjuvant chemotherapy (AT) on resected colon adenocarcinoma based on histologic subtype is poorly defined and extrapolated from patients with advanced disease. We evaluated the receipt and effect of AT on overall survival stratified by histologic subtype-mucinous, non-mucinous, and signet ring adenocarcinomas. A retrospective cohort study from 2004 to 2015 was conducted using the National Cancer Database. Patients with colon adenocarcinoma who underwent curative resection with pathologic stage III were included. Appendiceal and rectal tumors were excluded. The predictor variable was histologic subtype, and outcome variables were overall survival and receipt of AT. Absolute survival was increased for mucinous, non-mucinous, and signet ring tumors with receipt of AT (88.1, 108.9, and 38.1 months, respectively). In multivariable analysis, there was no difference in overall survival for mucinous patients relative to non-mucinous patients. In subgroup analysis, a modest survival advantage for non-mucinous patients relative to the mucinous patients was observed (HR, 0.92; 95% CI, 0.89-0.95). In multivariable modeling, non-mucinous and signet ring adenocarcinoma had decreased odds of receipt of AT relative to mucinous adenocarcinoma patients. Histologic subtype is an important prognostic factor for overall survival for stage III colon adenocarcinoma. Although the magnitude of the benefit of AT may vary in stage III curatively resected patients, it has a substantial survival benefit across all histologic subtypes. Based on these observations, there is no indication that patients with stage III mucinous adenocarcinoma of the colon should not receive AT. All patients with resected stage III colon cancer should be referred for AT regardless of histologic subtype.


The 5' untranslated region of Arabidopsis thaliana calmodulin cDNA is an independent cDNA containing an open reading frame.
A cDNA clone, pAUK1, with an open reading frame (ORF) coding for a hypothetical 164-amino-acid protein was isolated from an Arabidopsis thaliana (L.) Heynh cDNA library. The clone was attached, tail to tail, to the 3' end of A. thaliana hexokinase cDNA. An almost identical sequence had been previously described as the 5' untranslated region (5' UTR) of A. thaliana calmodulin cDNA (ACaM-2). Sequence comparison with three additional A. thaliana truncated cDNA clones which appear in a database (GenBank) supports the conclusion that pAUK1 is identical to the 5' UTR of ACaM-2 and that the 5' UTR of ACaM-2 is an independent cDNA artificially linked to A. thaliana calmodulin cDNA.


Mapping loci influencing the persistence of Theiler's virus in the murine central nervous system.
Inbred strains of mice differ greatly in their susceptibility to the demyelinating disease caused by Theiler's Murine Encephalomyelitis Virus. In this murine disease, which is an animal model for the study of multiple sclerosis, demyelination depends on the persistent infection of the central nervous system. Previous studies identified a locus in the H-2D region of the major histocompatibility complex which controls susceptibility to the persistent infection, and also showed that other loci are involved. In order to identify these loci, we screened the genome of a set of backcross animals with a combination of polymorphic microsatellites and restriction enzymes sites. We now show that viral persistence is also controlled by a locus close to Ifg on chromosome 10 and possibly by a locus near Mbp on chromosome 18.


Identification of quantitative trait loci for productive tiller number and its relationship to agronomic traits in spring wheat.
Productive tiller number (PTN), defined as the number of tillers that produce spikes and seeds, is a key component of grain yield in wheat. Spring wheat cultivars in the northern Great Plains of North America differ in PTN. The objectives of this study were (1) to determine the relationship of PTN to agronomic traits using recombinant inbred line (RIL) populations derived from crosses Reeder/Conan, McNeal/Thatcher and Reeder/McNeal grown under a range of environments, and (2) to identify and validate quantitative trait loci (QTL) associated with high PTN. Correlation between PTN and plot weight ranged from r = 0.4-0.6 among the populations based on combined means over years, and was positive in every environment for all crosses (P < 0.05). A genetic map generated for the Reeder/Conan RIL allowed identification of a QTL for PTN consistent over environments, located on chromosome 6B. The QTL on chromosome 6B (QTn.mst-6B) explained 9-17% of the variation of PTN and co-segregated with a QTL for yield in the Reeder/Conan RIL. QTn.mst-6B was validated by single marker analysis in the McNeal/Thatcher RIL, McNeal/Reeder RIL, and a set of near isogenic line (NIL) developed for QTn.mst-6B. The allele for high PTN significantly increased PTN by 8.7, 4, and 13% in the McNeal/Reeder RIL, McNeal/Thatcher RIL and Choteau/Reeder NIL, respectively. The allele for high PTN also had a significant positive effect on plot weight in the McNeal/Reeder RIL. Our results suggest that high PTN, controlled to a significant extent by QTn.mst-6B, contributed to increased yield potential over a range of environmental conditions. QTn.mst-6B may be useful for improving spring wheat in the northern Great Plains of North America and similar environments.


Stimulation of Ca2+ influx in alpha T3-1 gonadotrophs via the cAMP/PKA signaling system.
To investigate the regulation of free cytosolic calcium concentration ([Ca2+]i) by the adenosine 3',5'-cyclic monophosphate (cAMP) signaling system in clonal gonadotrophs, microfluorimetric recordings were made in single indo 1-loaded alpha T3-1 cells. Forskolin, 8-bromoadenosine 3',5'-cyclic monophosphate, or a low concentration (100 pM) of the hypothalamic factor pituitary adenylate cyclase-activating polypeptide (PACAP) stimulated Ca2+ step responses or repetitive Ca2+ transients, which were blocked by the removal of extracellular Ca2+ by the dihydropyridine (DHP) (+)PN 200-110 or by preincubation with the protein kinase A (PKA) antagonist H-89 (10 microM). Thus activation of the cAMP/PKA system in alpha T3-1 gonadotrophs stimulates Ca2+ influx through DHP-sensitive (L-type) Ca2+ channels. In contrast, high PACAP concentrations (100 nM) stimulated biphasic Ca2+ spike-plateau responses. The Ca2+ spike was independent of extracellular Ca2+, and similar responses were observed by microperfusion of individual cells with D-myo-inositol 1,4,5-trisphosphate, suggesting the involvement of the phospholipase C (PLC) signaling pathway. The Ca2+ plateau depended on Ca2+ influx, was blocked by (+)PN 200-110, but was only partially blocked by H-89 pretreatment. In conclusion, PACAP stimulates [Ca2+]i increases in alpha T3-1 gonadotrophs through both the PLC and adenylate cyclase signaling pathways. Furthermore, this is the first clear demonstration that the cAMP/PKA system can mediate changes in [Ca2+]i in gonadotroph-like cells.


Acylglycerol kinase promotes paclitaxel resistance in nasopharyngeal carcinoma cells by regulating FOXM1 via the JAK2/STAT3 pathway.
Drug resistance is an important factor that impedes the treatment of nasopharyngeal cancer (NPC). Acylglycerol kinase (AGK) has been found to be overexpressed in NPC and correlates with poor prognosis. Our objective was to demonstrate the effect of AGK on paclitaxel resistance in NPC and determine the underlying mechanisms. MTT assay was employed to determine the IC50 of paclitaxel in NPC cells after different treatments. Flow cytometry assays were employed to evaluate cell apoptosis. RT-qPCR and Western blot assays were used to detect alterations in mRNA and protein expression, respectively. Luciferase assays and chromatin immunoprecipitation (ChIP) assays were used to determine the relationship between and the regulatory effect of STAT3 on the promoter of FOXM1. AGK was elevated in paclitaxel-resistant NPC cells, and knockdown of AGK suppressed the resistance of CNE1-TR and CNE2-TR cells to paclitaxel. Moreover, upregulation of FOXM1 rescued the effects of AGK knockdown. Furthermore, the JAK2/STAT3 signalling pathway was overactivated in CNE1-TR and CNE2-TR cells, and knockdown of AGK suppressed JAK2/STAT3 signalling. STAT3 was verified to bind to and activate the promoter region of FOXM1. An in vivo tumour xenograft assay also verified that AGK knockdown inhibited tumour growth and mitigated paclitaxel resistance by regulating the JAK2/STAT3/FOXM1 axis. AGK levels were increased in paclitaxel-resistant NPC cells. AGK activates JAK2/STAT3 signalling, thus promoting FOXM1 transcription and eventually enhancing the drug resistance of NPC cells.


[Local therapy with capsaicin or ASS in chronic pain].
To provide a brief review of the current state of topical treatment with capsaicin or acetylsalicylic acid (ASA) for therapy of chronic pain syndromes. A MEDLINE search was used to find the pertinent literature on "capsaicin" or "ASA" and "chronic pain"; further publications found in these articles were added. Capsaicin is a white crystalline parent compound of a group of vanillyl fatty acid amines. Because of its highly specific action in neurons it has become an important tool in neuroscience. Because of its effects, it is obvious to try for the therapy of circumscribed neuropathic pain. Capsaicin acts by depleting stores of substance P and other neurotransmitters, resulting in a blockade of a specific group of sensory afferents. The corresponding clinical findings are initial burning and a desensitization of specific C fiber nociceptors after repeated application. The pain relieving potency was observed in various clinical investigations and even in a few controlled, double-blind studies about neuropathic pain syndromes and (osteo)arthritis. In contrast to these findings, a recent study found no significant benefit of capsaicin, probably because this study was the first to use an active placebo. Therefore, and because clinical efficacy and advantages over other therapies have not been demonstrated up to now, capsaicin cannot be classified as standard therapy. It may be a therapeutic option as an alternative or as an adjuvant treatment. Pain reduction was also observed after topical application of ASA/ether mixture in the one and only controlled double-blind study on this issue. Therefore, topical ASA therapy for (post)herpetic neuralgia is mainly based on a few enthusiastic case reports rather than on well founded investigations. Furthermore, the discrimination of local from systemic effects, the toxicological profile of longterm topical treatment, and the mechanism of action has not been evaluated. In conclusion, topical ASA cannot be recommended for routine clinical use at present.


Minimal Clinically Important Differences in Inspiratory Muscle Function Variables after a Respiratory Muscle Training Programme in Individuals with Long-Term Post-COVID-19 Symptoms.
To establish the minimal clinically important difference (MCID) for inspiratory muscle strength (MIP) and endurance (IME) in individuals with long-term post-COVID-19 symptoms, as well as to ascertain which of the variables has a greater discriminatory capacity and to compare changes between individuals classified by the MCID. Secondary analysis of randomised controlled trial of data from 42 individuals who performed an 8-week intervention of respiratory muscle training programme. A change of at least 18 cmH2O and 22.1% of that predicted for MIP and 328.5s for IME represented the MCID. All variables showed acceptable discrimination between individuals who classified as "improved" and those classified as "stable/not improved" (area under the curve ≥0.73). MIP was the variable with the best discriminative ability when expressed as a percentage of prediction (Youden index, 0.67; sensitivity, 76.9%; specificity, 89.7%). Participants classified as "improved" had significantly greater improvements in quality of life and lung function compared with the participants classified as "stable/not improved". In individuals with long-term post-COVID-19 symptoms, the inspiratory muscle function variables had an acceptable discriminative ability to assess the efficacy of a respiratory muscle training programme. MIP was the variable with the best discriminative ability, showing better overall performance when expressed as a percentage of prediction.


Solitary breast mass as initial presentation of clinically silent metastatic renal cell carcinoma.
Metastasis to the breast from extramammary tumors is rare. Breast metastases of renal cell carcinoma (RCC) origin have been described in sporadic case reports. We present a patient with a solitary breast mass representing the manifestation of clinically silent, metastatic RCC. A 76-year-old female was 12 years prior removed from radical nephrectomy for localized RCC. Her new breast mass was identified on physical examination. Pathology of the resected mass was diagnostic of metastatic RCC and subsequent imaging studies demonstrated a 1.9 cm renal mass in her solitary kidney. The patient elected subcutaneous Interleukin-2 immunotherapy as primary treatment for her recurrent RCC.


Substrate-mediated purification and characterization of a 3-hydroxybenzoic acid-6-hydroxylase from Micrococcus.
3-Hydroxybenzoic acid-6-hydroxylase from Micrococcus sp. was purified to homogeneity in a single step using the substrate-mediated interaction of the enzyme with blue-Sepharose. The enzyme was bound to the affinity matrix in the presence of 3-hydroxybenzoic acid and was eluted in its absence. The molecular weight of the purified enzyme is 70,000 with no subunit structure. The flavoenzyme required the exogenous addition of FAD for its complete activity and had a strict preference for NADH over NADPH. The activity of the enzyme was drastically inhibited by Cu2+ and Hg2+ and the inhibition was reversed by thiol reagents.


PCSK9 genetic (rs11591147) and epigenetic (DNA methylation) modifications associated with PCSK9 expression and serum proteins in CAD patients.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) genetic polymorphisms play a significant role in cholesterol homeostasis. Therefore, we aimed to investigate the association of PCSK9 genetic variations NM_174936.3:c.137G>T (R46L, rs11591147) and NM_174936.3:c.1120G>T (D374Y, rs137852912), as well as promoter DNA methylation status, with mRNA expression and circulating serum protein levels in coronary artery disease (CAD) patients. The present study includes 300 CAD cases and 300 controls from South India. Biochemical assays were performed using commercially available kits. PCSK9 rs11591147 and rs137852912 polymorphisms were analyzed by the polymerase chain reaction (PCR)-restriction fragment length polymorphism method, whereas promoter DNA methylation status and gene expression were determined using methylation specific PCR and quantitative PCR respectively. The genotypic distribution of PCSK9 rs11591147 revealed that individuals with the TT-genotype and T-allele have a reduced risk for CAD. Furthermore, patients with the PCSK9 rs11591147 TT genotype have a significantly lower total cholesterol and low-density lipoprotein-cholesterol levels and also higher high-density lipoprotein-cholesterol levels than individuals with the GG genotype. Logistic regression analysis has shown that the GG and GT (p = 1.51 × 10-8 , p = 1.47 × 10-9 ) genotypes predicted the risk for CAD with an odds ratio of 5.8 and 7.3 respectively. In addition, individuals with the TT genotype were hypermethylated at promoter DNA of PCSK9, resulting in lower mRNA expression and circulating serum proteins than in individuals with the GG genotype. In silico analyses revealed that rs11591147 T-allele has protein destabilizing capacity. In conclusion, the present study indicates that the PCSK9 gene expression and circulating serum protein levels are not only associated with rs11591147 genotype, but also with promoter DNA methylation. Furthermore, the findings with respect to both single nucleotide polymorphism and promoter DNA methylation may open avenues for novel treatment possibilities targeting PCSK9 for CAD management.


Effects of calcium binding on the structure and stability of human growth hormone.
Thermodynamic analysis of calcium ions binding to human growth hormone (hGH) was done at 27 degrees C in NaCl solution, 50 mM, using different techniques. The binding isotherm for hGH-Ca2+ was obtained by two techniques of ionmetry, using a Ca(2+)-selective membrane electrode, and isothermal titration calorimetry. Results obtained by two ionmetric and calorimetric methods are in good agreement. There is a set of three identical and non-interacting binding sites for calcium ions. The intrinsic dissociation equilibrium constant and the molar enthalpy of binding are 52 microM and -17.4 kJ/mol, respectively. Temperature scanning UV-vis spectroscopy was applied to elucidate the effect of Ca2+ binding on the protein stability, and circular dichroism (CD) spectroscopy was used to show the structural change of hGH due to the metal ion interaction. Calcium ions binding increase the protein thermal stability by increasing of the alpha helix content as well as decreasing of both beta and random coil structures.


Phenotyping reproductive stage chilling and frost tolerance in wheat using targeted metabolome and lipidome profiling.
Frost events lead to A$360 million of yield losses annually to the Australian wheat industry, making improvement of chilling and frost tolerance an important trait for breeding. This study aimed to use metabolomics and lipidomics to explore genetic variation in acclimation potential to chilling and to identify metabolite markers for chilling tolerance in wheat. We established a controlled environment screening assay that is able to reproduce field rankings of wheat germplasm for chilling and frost tolerance. This assay, together with targeted metabolomics and lipidomics approaches, were used to compare metabolite and lipid levels in flag leaves of two wheat varieties with contrasting chilling tolerance. The sensitive variety Wyalkatchem showed a strong reduction in amino acids after the first cold night, followed by accumulation of osmolytes such as fructose, glucose, putrescine and shikimate over a 4-day period. Accumulation of osmolytes is indicative of acclimation to water stress in Wyalkatchem. This response was not observed for tolerant variety Young. The two varieties also displayed significant differences in lipid accumulation. Variation in two lipid clusters, resulted in a higher unsaturated to saturated lipid ratio in Young after 4 days cold treatment and the lipids PC(34:0), PC(34:1), PC(35:1), PC(38:3), and PI(36:4) were the main contributors to the unsaturated to saturated ratio change. This indicates that Young may have superior ability to maintain membrane fluidity following cold exposure, thereby avoiding membrane damage and water stress observed for Wyalkatchem. Our study suggests that metabolomics and lipidomics markers could be used as an alternative phenotyping method to discriminate wheat varieties with differences in cold acclimation.


Symptomatic pancreatic polypeptide-secreting tumor of the distal pancreas (PPoma).
Our report describes a 46-yr-old woman who presented with watery diarrhea in the presence of multiple endocrine neoplasia type I (MEN I) syndrome. Of various potential pancreatic endocrine hormones, only serum levels of pancreatic polypeptide were elevated. Radiologic imaging failed to identify a pancreatic tumor; her diarrhea was therefore managed with subcutaneous administration of somatostatin. Three years later she developed gallstone pancreatitis with the subsequent development of a pancreatic pseudocyst. At exploration for drainage of the pseudocyst, intraoperative ultrasound identified a 6-mm tumor in the distal pancreas that was resected. Final pathology documented a pancreatic endocrine tumor with immunohistochemical staining demonstrating the presence of pancreatic polypeptide. The present case illustrates the symptomatology that may be associated with pancreatic polypeptide-secreting endocrine tumors of the pancreas.


Mortality of eating disorders: a follow-up study of treatment in a specialist unit 1974-2000.
To study excess mortality, causes of death, and co-morbidity in patients with eating disorder (ED), treated in a Swedish specialist facility. A retrospective cohort study of 201 patients with ED followed from 1974 to year 2001 in the Swedish Causes of Death Register (SCODR). Standardized mortality ratio (SMR) was calculated with respect to the Swedish population, by gender, age, and calendar time. In the complete follow-up of 201 patients, 23 had died. At a mean follow-up of 14.3 years the overall SMR was 10. Patients with body mass index (BMI) over 11.5 had an average SMR of about 7 and for those with BMI lower than 11.5 had SMR above 30. Six patients died from AN/starvation, nine due to suicide, and eight from other causes. SMR in anorexia nervosa (AN) is high but not in bulimia nervosa. A risk stratification of AN, based on BMI is suggested.


Association of genetic predisposition to obesity with type 2 diabetes risk in Han Chinese individuals.
Obesity is a major risk factor for type 2 diabetes, but little is known about the contribution of BMI-associated loci to type 2 diabetes risk in East Asian populations. In this study, 30 known BMI-associated variants and a genetic risk score (GRS) calculated by summing the BMI-increasing alleles of these variants were tested for associations with type 2 diabetes and related glycaemic traits in 1,873 cases of type 2 diabetes and 1,839 controls in Han Chinese individuals. Logistic and linear regression analyses were performed to determine the association with type 2 diabetes risk or related glycaemic traits, respectively, under an additive model with or without adjustment for BMI. The GRS was significantly associated with increased BMI (β [SE] 0.070 [0.016]; p = 1.33 × 0(-5)) in the overall population. Each additional BMI-increasing allele in the GRS increased type 2 diabetes risk by 1.029-fold (95% CI 1.008, 1.050; p = 0.0056) without adjustment for BMI, and the association was slightly attenuated after adjustment for BMI (OR 1.022; 95% CI 1.002, 1.043; p = 0.035). In non-diabetic controls, the GRS was also associated with HOMA of beta cell function (HOMA-B) with adjustment for BMI (β [SE] -0.876 [0.345]; p = 0.011). Notably, the association of GRS with type 2 diabetes was abolished after adjusting for HOMA-B (OR 1.012; 95% CI 0.986, 1.039; p = 0.380). Our results suggested that genetic predisposition to obesity leads to increased risk of type 2 diabetes, independent of BMI and partly through impaired beta cell function.


[Evaluation of the prescription of long-term systemic steroid-therapy associated measures].
To prevent the occurrence of corticosteroid's side effects, adjuvant measures are prescribed in a very different way depending on the practitioner's experience. The aim of this study was to assess the physicians' practices regarding the prescription of long-term corticosteroid therapy. In May 2010, we realized a cross-sectional study among physicians in Ibn Sina University Hospital in Rabat. With a data collection form, we assessed the principal indications for prescribing steroids and the frequency of prescription of measures sometimes associated with systemic corticosteroid. Fifty-nine out of eighty physicians completed the data collection form (response rate: 69.4%). Calcium-vitamin D supplementation was recommended by most of the physicians. Half of them were prescribing biphosphonate therapy. Most of them propose a low-sodium, a low-fat and a low-carbohydrate dietary regimen. Regular physical exercise was recommended by 35% of physicians. Gastric protection was indicating by 54.4% of practicians and potassium supplementation by 42.1% of them. Finally, the recommendation for influenza vaccination, hydrocortisone prescription and Synacthen(®) test, varied between physicians. The prescription of adjuvant measures with a long-term corticosteroid therapy was very heterogeneous. There is no consensus regarding most of the measures.


Characteristics of endoplasmic reticulum stress in colorectal cancer for predicting prognosis and developing treatment options.
An increasing body of evidence supports an essential role for endoplasmic reticulum stress (ERS) in colorectal cancer (CRC). In this study, we developed an ERS-related genes (ERSRGs) model to aid in the prognostic evaluation and treatment of CRC patients. The training set and validation set data were extracted from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), respectively. ERSRGs were obtained from the GeneCards database. A prognostic risk scoring model was constructed using the least absolute shrinkage and selection operator (LASSO) along with univariate Cox regression analysis. To further predict the probability of survival for patients at 1, 2, and 3 years, a nomogram was devised. The advantages of the prognostic risk score model in screening patients' sensitive to chemotherapy and immunotherapy were analyzed by drug sensitivity analysis and immune correlation analysis. Finally, hub genes associated with poor prognosis in the risk model were screened by Protein-protein interaction (PPI) network and their expression was validated using clinical specimens. A risk model for overall survival (OS) was developed using 16 ERSRGs associated with prognosis. Through analyses, we demonstrated a high degree of reliability for the prognostic risk scoring model. The constructed nomograms performed well in predicting patient survival over 1, 3, and 5 years. The calibration curve and decision curve analysis (DCA) supported a high degree of accuracy for the model. Patients in the low-risk group had a lower IC50 for the common chemotherapy drug, 5-FU, and responded better to immunotherapy. hub poor prognostic genes were validated in CRC clinical specimens. We have identified and validated a new ERS prognostic marker that can accurately predict the survival status of CRC patients for clinicians and better provide personalized treatment plans.


The list system can reduce the waiting time and number of consultations in a centralized primary care centre that provides out of hours medical care.
To study the waiting time and number of consultations of the patients who required out of hours medical care from a centralized primary care centre before and after the introduction of a list system. Non-controlled intervention study. A questionnaire, completed by receptionists, concerning all out of hours general practice consultations for one week each month during two separate years (in 1990 with no list system and in 1993 with list system in operation). One health centre in central Finland in a region with 39495 inhabitants. All patients contacting the health centre to request medical help during out of hours work. Consultation rates by age and sex of the patients and their waiting time before seeing the GP. In 1990, the average out of hours consultation rate per 1000 inhabitants per year was 826 for women and 819 for men. These figures were reduced by 271 for women (95% CI 262-280) and 305 for men (95% CI 297-314) in 1993. The mean waiting time was 55 min in 1990 and 32 min in 1993 (p < 0.001). The introduction of a list system leads to more effective primary care services.


Post-COVID-19 co-morbidity of emerged Lophomonas infection and invasive pulmonary aspergillosis: First case report.
Due to long corticosteroid therapy in patients with COVID-19, in case of cough, dyspnea, and weight loss, emerging pulmonary aspergillosis and lophomoniasis should be ruled out.


Translation and adaptation of the Radiotherapy Edema Rating Scale to Brazilian Portuguese.
Internal lymphedema is one of the sequelae of head and neck cancer treatment that can lead to varying degrees of swallowing, speech, and respiration alterations. The Radiotherapy Edema Rating Scale, developed by Patterson et al., is a tool used to evaluate pharyngeal and laryngeal edema. To translate into Brazilian Portuguese, to culturally adapt and test this scale in patients undergoing treatment for head and neck cancer. The process followed the international guidelines and translation steps by two head and neck surgeons and back-translation performed independently by two North-American natives. The final version of the test was evaluated based on the assessment of 18 patients by two head and neck surgeons and two speech therapists using the scales in Brazilian Portuguese. The translation and cultural adaptation were satisfactorily performed by the members of the committee in charge. The translation and adaptation into Brazilian Portuguese of the Radiotherapy Edema Rating Scale was successfully performed and showed to be easy to apply.


Spontaneous dissecting aneurysm of the extracranial vertebral artery (20 cases).
Spontaneous dissecting aneurysm of the vertebral artery is an infrequent cause of vertebro basilar ischemic strokes. Previously reported cases concern essentially occlusion of the basilar artery. Only 14 cases of spontaneous dissecting aneurysm concern the extracranial vertebral artery among these eight were angiographically documented. In this study based upon 15 patients (20 dissecting aneurysms), the authors discuss etiological factors, such as hypertension or fibromuscular dysplasia: on clinical findings they insist upon the diagnostic value of preliminary symptoms, cervical pain or posterior headaches; the most frequent angiographic appearance was a long and irregular stenosis of one or two segments of the vertebral artery. The prognosis of these aneurysms most often appears favourable in this group.


Phosphatidylcholine-induced reactivation of photosystem II membranes pretreated with Triton X-100.
Triton X-100-induced inactivation and phosphatidylcholine-induced reactivation of photosystem II (PSII) membranes were investigated using oxygen electrode, variable fluorescence and spectroscopic techniques including absorption and circular dichroism spectroscopy. Incubation of the PSII membrane with Triton X-100 reduced the oxygen-evolving rate, modified the variable chlorophyll fluorescence kinetics, changed the protein secondary structures, altered the chlorophyll binding state to proteins and decreased the excitonic interaction of chlorophyll molecules. Phosphatidylcholine addition did not change the protein secondary structures, but could partially reactivate the reduced oxygen-evolving rate, and partly reversed the variable fluorescence parameters, the chlorophyll binding state and the excitonic interaction of the chlorophyll molecules. The results indicate that the phosphatidylcholine environment can optimize the tertiary structures of PSII.


Robotic proctectomy for rectal cancer: analysis of 71 patients from a single institution.
Despite increasing use of robotic surgery for rectal cancer, few series have been published from the practice of generalizable US surgeons. A retrospective chart review was performed for 71 consecutive patients who underwent robotic low anterior resection (LAR) or abdominoperineal resection (APR) for rectal adenocarcinoma between 2010 and 2014. 46 LARs (65%) and 25 APRs (35%) were identified. Median procedure time was 219 minutes (IQR 184-275) and mean blood loss 164.9 cc (SD 155.9 cc). Radial margin was negative in 70/71 (99%) patients. Total mesorectal excision integrity was complete/near complete in 38/39 (97%) of graded specimens. A mean of 16.8 (SD+/- 8.9) lymph nodes were retrieved. At median follow-up of 21.9 months, there were no local recurrences. Robotic proctectomy for rectal cancer was introduced into typical colorectal surgery practice by a single surgeon, with a low conversion rate, low complication rate, and satisfactory oncologic outcomes.


Genetic epistasis between heparan sulfate and FGF-Ras signaling controls lens development.
Vertebrate lens development depends on a complex network of signaling molecules to coordinate cell proliferation, migration and differentiation. In this study, we have investigated the role of heparan sulfate in lens specific signaling by generating a conditional ablation of heparan sulfate modification genes, Ndst1 and Ndst2. In this mutant, N-sulfation of heparan sulfate was disrupted after the lens induction stage, resulting in reduced lens cell proliferation, increased cell death and defective lens fiber differentiation in later lens development. The loss of Ndst function also prevented the assembly of Fgf/Fgfr complexes on the lens cell surface and disrupted ERK signaling within the lens. We further demonstrated that Ndst mutation completely inhibited the FGF1 and Fgf3 overexpression phenotypes, but Kras reactivation was sufficient to reverse the Ndst deficient lens differentiation defect. The epistatic relationship between Ndst and FGF-Ras signaling demonstrates that FGF signaling is the predominant signaling pathway controlled by Ndst in lens development.


Estimating perceived parental substance use disorder: Using register data to adjust for non-participation in survey research.
To estimate the prevalence of parental substance use disorder (PSUD) in the general population based on young adults' reports adjusted for non-participation using register-based indicators of PSUD. A national sample survey study combined with a retrospective register-based study. Setting Denmark. Participants 10,414 young people (aged 15-25 years) invited to two national sample surveys in 2014 and 2015 (5,755 participants and 4,659 non-participants). A crude prevalence of PSUD was calculated based on participants' reports. Parental data from medical, mortality, prescription, and treatment registers (from the young adults' birth until the time of the surveys) were used to estimate a register-based prevalence of PSUD for both participants and non-participants. Differences between participants and non-participants were analysed using bivariate comparisons. Inverse probability weighting was used to adjust for bias due to non-participation. The crude prevalence of PSUD based on survey data was adjusted using the ratio of incidence proportion of the register-based PSUD compared with the survey-based PSUD. A total of 731 (12.7%) of the 5,755 survey participants reported PSUD. Register-based PSUD was more common among non-participants (856/4,659; 18.4%) compared with participants (738/5,755; 12.8%, OR = 1.53, 95% CI 1.38-1.70). The adjusted estimate of the survey-based PSUD increased by 2.5 percentage points, from 12.7% to 15.2%. In the absence of register data, youth-reported PSUD is likely to underestimate the number of young people experiencing PSUD.


Nasal delivery of nanoliposome-encapsulated ferric ammonium citrate can increase the iron content of rat brain.
Iron deficiency in children can have significant neurological consequences, and iron supplementation is an effective treatment of choice. However, traditional routes of iron supplementation do not allow efficient iron delivery to the brain due to the presence of the blood-brain barrier. So an easily delivered iron formulation with high absorption efficiency potentially could find widespread application in iron deficient infants. In this study, we have developed and characterized a nanovesicular formulation of ferric ammonium citrate (ferric ammonium citrate nanoliposomes, FAC-LIP) and have shown that it can increase brain iron levels in rats following nasal administration. FAC was incorporated into liposomes with high efficiency (97%) and the liposomes were small (40 nm) and stable. Following intranasal delivery in rats, FAC-LIP significantly increased the iron content in the olfactory bulb, cerebral cortex, striatum, cerebellum and hippocampus, and was more efficient at doing so than FAC alone. No signs of apoptosis or abnormal cell morphology were observed in the brain following FAC-LIP administration, and there were no significant changes in the levels of SOD and MDA, except in the cerebellum and hippocampus. No obvious morphological changes were observed in lung epithelial cells or tracheal mucosa after nasal delivery, suggesting that the formulation was not overtly toxic. In this study, nanoscale FAC-LIP proved an effective system delivering iron to the brain, with high encapsulation efficiency and low toxicity in rats. Our studies provide the foundation for more detailed investigations into the applications of niosomal nasal delivery of liposomal formulations of iron as a simple and safe therapy for iron deficiency anemia. Graphical abstract The diagrammatic sketch of "Nasal delivery of nanoliposome-encapsulated ferric ammonium citrate can increase the iron content of rat brain". Nanoliposome-encapsulated ferric ammonium citrate (FAC-LIP) was successfully prepared and intranasal administration of FAC-LIP increased both the total iron contents and iron storage protein (FTL) expression in rat olfactory bulb, cerebral cortex, striatum and hippocampus, compared with those of FAC groups. Moreover, there was not overtly toxic affects to brain, lung epithelial cells and tracheal mucosa.


Biodegradation of 4-bromophenol by Arthrobacter chlorophenolicus A6T in a newly designed packed bed reactor.
Bromophenol is listed as a priority pollutant by the U.S. EPA. However, there has been no report on the removal of bromophenol in any biological system that is operated in a continuous mode. The efficiency of Arthrobacter chlorophenolicus A6(T) on the biodegradation of 4-bromophenol (4-BP) in a newly designed packed bed reactor (PBR) was evaluated with different influent 4-BP concentrations between 400 mg l(-1) and 1200 mg l(-1) and hydraulic retention times (HRTs) between 24 h and 7.5 h. The response of the PBR to 4-BP shock loadings was also tested, and the bioreactor was found to adequately handle these shock loadings. The percentage of effluent toxicity in the PBR was tested using mixed microbial consortia as the test species; this experiment was performed using a 4-BP influent concentration of 1200 mg l(-1) and HRTs between 24 h and 7.5 h. A maximal 98% effluent toxicity removal was achieved when the PBR was operated at an HRT of 24 h. In the present study, 4-BP was used as the sole source of carbon and energy, and the complete removal of 4-BP was achieved with 4-BP loading rates of up to 2277 mg l(-1) day(-1).


Dynamics of interfacial layers-experimental feasibilities of adsorption kinetics and dilational rheology.
Each experimental method has a certain range of application, and so do the instruments for measuring dynamic interfacial tension and dilational rheology. While the capillary pressure tensiometry provides data for the shortest adsorption times starting from milliseconds at liquid/gas and tens of milliseconds at liquid/liquid interfaces, the drop profile tensiometry allows measurements in a time window from seconds to many hours. Although both methods together cover a time range of about eight orders of magnitude (10(-3) s to 10(5) s), not all surfactants can be investigated with these techniques in the required concentration range. The same is true for studies of the dilational rheology. While drop profile tensiometry allows oscillations between 10(-3) Hz and 0.2 Hz, which can be complemented by measurements with capillary pressure oscillating drops and the capillary wave damping method (up to 10(3) Hz) these six orders of magnitude in frequency are often insufficient for a complete characterization of interfacial dilational relaxations of surfactant adsorption layers. The presented analysis provides a guide to select the most suitable experimental method for a given surfactant to be studied. The analysis is based on a diffusion controlled adsorption kinetics and a Langmuir adsorption model.


Proteomic and N-Terminomic TAILS Analyses of Human Alveolar Bone Proteins: Improved Protein Extraction Methodology and LysargiNase Digestion Strategies Increase Proteome Coverage and Missing Protein Identification.
With 2129 proteins still classified by the Human Proteome Organisation Human Proteome Project (HPP) as "missing" without compelling evidence of protein existence (PE) in humans, we hypothesized that in-depth proteomic characterization of tissues that are technically challenging to access and extract would yield evidence for tissue-specific missing proteins. Paradoxically, although the skeleton is the most massive tissue system in humans, as one of the poorest characterized by proteomics, bone falls under the HPP umbrella term as a "rare tissue". Therefore, we aimed to optimize mineralized tissue protein extraction methodology and workflows for proteomic and data analyses of small quantities of healthy young adult human alveolar bone. Osteoid was solubilized by GuHCl extraction, with hydroxyapatite-bound proteins then released by ethylenediaminetetraacetic acid demineralization. A subsequent GuHCl solubilization extraction was followed by solid-phase digestion of the remaining insoluble cross-linked protein using trypsin and then 6 M urea dissolution incorporating LysC digestion. Bone extracts were digested in parallel using trypsin, LysargiNase, AspN, or GluC prior to liquid chromatography-mass spectrometry analysis. Terminal Amine Isotopic Labeling of Substrates was used to purify semitryptic peptides, identifying natural and proteolytic-cleaved neo N-termini of bone proteins. Our strategy enabled complete solubilization of the organic bone matrix leading to extensive categorization of bone proteins in different bone matrix extracts, and hence matrix compartments, for the first time. Moreover, this led to the high confidence identification of pannexin-3, a "missing protein", found only in the insoluble collagenous matrix and revealed for the first time by trypsin solid-phase digestion. We also found a singleton proteotypic peptide of another missing protein, meiosis inhibitor protein 1. We also identified 17 proteins classified in neXtprot as PE1 based on evidence other than from MS, termed non-MS PE1 proteins, including ≥9-mer proteotypic peptides of four proteins.


Research on the Influence of Media Internalized Pressure on College Students' Sports Participation-Chained Intermediary Analysis of Social Physique Anxiety and Weight Control Self-Efficacy.
Purpose: Discuss the relationship among college students' media internalized pressure, social physique anxiety, weight control self-efficacy, and sports participation in providing a reference for promoting college students to develop healthy and confident living habits. Methods: Take Southwest University in China as the object, select the subjects by stratified random sampling, and process the data with SPSS19.0 and AMOS21.0 statistical software. Results: (1) Media internalized pressure is positively correlated with social physique anxiety, weight control self-efficacy, and sports participation; social physique anxiety is significantly positively correlated with weight control self-efficacy and sports participation, and weight control self-efficacy is significantly positively correlated with sports participation; (2) media internalized pressure has a direct effect on sports participation (ES = 0.456), and social physique anxiety (ES = 0.136) and weight control self-efficacy (ES = 0.102) play significant mediating roles in the relationship between media internalized pressure and sports participation, respectively; the chained mediating force of social physique anxiety and weight control self-efficacy also reaches a significant level (ES = 0.027). Conclusion: Media internalized pressure can influence college students' sports participation through the direct path as well as indirect paths such as social physique anxiety, the intermediary effect of weight control self-efficacy, and chained intermediary effect of social physique anxiety-weight control self-efficacy, and social physique anxiety is another key factor affecting college students' sports participation except media internalized pressure.


Young children mostly keep, and expect others to keep, their promises.
Promises are speech acts that create an obligation to do the promised action. In three studies, we investigated whether 3- and 5-year-olds (N=278) understand the normative implications of promising in prosocial interactions. In Study 1, children helped a partner who promised to share stickers. When the partner failed to uphold the promise, 3- and 5-year-olds protested and referred to promise norms. In Study 2, when children in this same age range were asked to promise to continue a cleaning task-and they agreed-they persisted longer on the task and mentioned their obligation more frequently than without such a promise. They also persisted longer after a promise than after a cleaning reminder (Study 3). In prosocial interactions, thus, young children feel a normative obligation to keep their promises and expect others to keep their promises as well.


Oral Vaccination with Hepatitis E Virus Capsid Protein and Immunobiotic Bacterium-Like Particles Induce Intestinal and Systemic Immunity in Mice.
The hepatitis E virus (HEV) genotype 3 (GT3) is an emergent pathogen in industrialized countries. It is transmitted zoonotically and may lead to chronic hepatitis in immunocompromised individuals. We evaluated if the major antigen of HEV, the capsid protein, can be used in combination with immunobiotic bacterium-like particles (IBLP) for oral vaccination in a mouse model. We have cloned and expressed the RGS-His5-tagged HEV GT3 capsid protein (ORF2) in E. coli and purified it by NiNTA. IBLP were obtained from two immunobiotic Lactobacillus rhamnosus strains acid- and heat-treated. ORF2 and the IBLP were orally administered to Balb/c mice. After three oral immunizations (14-day intervals), blood, intestinal fluid, Peyer´s patches, and spleen samples were drawn. IgA- and IgG-specific antibodies were determined by ELISA. Mononuclear cell populations from Peyer's patches and spleen were analyzed by flow cytometry, and the cytokine profiles were determined by ELISA to study cellular immunity. Orally administered recombinant ORF2 and IBLP from two L. rhamnosus strains (CRL1505 and IBL027) induced both antigen-specific humoral and cellular immune responses in mice. IBLP027 was more effective in inducing specific secretory IgA in the gut. IFN-γ, TNF-α, and IL-4 were produced by Peyer's plaques lymphocytes stimulated with ORF2 ex vivo suggesting a mixed Th1/Th2-type adaptive immune response in immunized mice. Oral vaccines are not invasive, do not need to be administered by specialized personal, and elicit both systemic and local immune responses at the port of entry. Here, we present an experimental oral vaccine for HEV GT3, which could be further developed for human and/or veterinary use.


Flavobacterium meningosepticum infection in a neonatal ward.
An outbreak of infections due to Flavobacterium meningosepticum type C in a neonatal intensive care unit is described. During a period of two weeks, two infants developed meningitis and a third was colonized in the respiratory tract and had transient bacteremia. The two meningitis patients were treated with clindamycin, rifampicin and cefotaxime systemically, plus rifampicin intraventricularly. Bacteriological eradication was achieved within 48 h, and both infants recovered from the meningitis without apparent neurological sequelae; however, one infant died two months later of unrelated causes. Environmental surveillance cultures failed to demonstrate a reservoir for the epidemic strain, but other Flavobacterium strains were recovered. Two clinically healthy infants were found to be colonized in the nasopharynx with strains that were extremely difficult to differentiate phenotypically from the epidemic strain. Extensive characterization of strains is necessary in order to differentiate between strains and subsequently to determine a certain source of infection.