Gastric transposition in head and neck surgery. Indications, complications, and expectations.
From 1973 through 1982 a total of 63 of our patients had their upper alimentary tracts reconstructed after major ablative neck operations by transposition of the mobilized stomach into the neck through the bed of the resected esophagus. This gastric pull-up procedure was performed without thoracotomy using two surgical teams for resection of locally extensive primary tumors arising in the hypopharynx, cervical esophagus, and thyroid gland. Morbidity and mortality were significant but acceptable. Relatively few patients were cured, but excellent palliation was often achieved. In our experience, use of the transposed stomach for restoration of alimentary continuity after cervical esophagectomy or circumferential pharyngectomy offered greater reliability and versatility than other available methods.


Correlation of serum zinc levels with pathological and laboratory findings in patients with nonalcoholic fatty liver disease.
Chronic liver diseases are associated with zinc (Zn) deficiency. However, no previous studies have examined the relationship between serum Zn levels and hepatic pathological findings in patients with nonalcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the serum Zn levels in NAFLD patients based on pathological/laboratory findings. We evaluated a total of 191 NAFLD patients who underwent liver biopsy with the goal of identifying laboratory markers and pathological findings associated with serum Zn levels. Zn levels significantly decreased along with progression of hepatic fibrosis (P = 0.039), but there were no significant differences among inflammatory grades. Zn levels were most strongly correlated with albumin levels (r = 0.410, P < 0.001). In addition, Zn levels were significantly correlated with homeostasis model assessment of insulin resistance (HOMA-IR) (r = -0.284, P < 0.001), hyaluronic acid (r = -0.230, P < 0.001), branched chain amino acid/tyrosine molar ratio (BTR) (r = 0.278, P < 0.001), FIB-4 index (r = -0.238, P < 0.001), and NAFLD fibrosis score (NFS) (r = -0.261, P < 0.001). In multivariate analysis, albumin [odds ratio (OR), 9.244 (per 1 g/dL decrease) [95% confidence interval (CI), 2.261-32.744]; P < 0.001], BTR [OR, 1.545 (per 1 decrease) (95% CI, 1.115-2.140); P = 0.009], and HOMA-IR [OR, 1.048 (per 1 increase) (95% CI, 1.019-1.167); P = 0.028] were significantly associated with Zn deficiency. The progression of liver fibrosis, but not inflammation, is associated with lower serum Zn levels in biopsy-proven NAFLD patients. Serum Zn levels were correlated with nutrition markers and insulin resistance.


A systemic response of geophytes is demonstrated by patterns of protein expression and the accumulation of signal molecules in Zantedeschia aethiopica.
In geophyte plants, such as Zantedeschia, individual leaves are directly connected to a specialized underground storage organ (rhizome/tuber), raising a question regarding systemic resistance as a mechanism of defense. A systemic response requires a transfer of a signal through the storage organ which has been evolutionary adapted to store food, minerals and moisture for seasonal growth and development. We have characterized the nature of induced defense responses in Zantedeschia aethiopica, a rhizomatous (tuber-like) ornamental plant by the application of local elicitation using two well-known defense elicitors, benzo-(1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester (BTH) and methyl jasmonate (MJ). The system consisted leaves in which local responses were directly induced, and systemically responsive leaves in which defense molecules were detected, demonstrating a transported vascular signal. Using anatomical and biochemical tools and local elicitation with MJ, the systemic nature of the response was verified in adjacent leaves by unique protein expression patterns; similarly polyphenol oxidase (PPO) activity was found to increase systemically in all parts of the locally induced plants, including the rhizome, and adjacent leaves; finally, significant accumulation of defense signal molecules such as salicylic and jasmonic acids was recorded in local and systemic leaves following elicitation with BTH. Anatomical sections through the leaves and the rhizome revealed that to be transferred from one leaf to its neighbor, signal molecules must have been transferred through the storage organ. The collected data strongly support our hypothesis that defense signals may and are transferred through the storage organ in monocot geophytes.


The association of chronic kidney disease and dialysis treatment with foot ulceration and major amputation.
The objective of this study was to investigate the risk of chronic kidney disease (CKD) stage 4-5 and dialysis treatment on incidence of foot ulceration and major lower extremity amputation in comparison to CKD stage 3. In this retrospective study, all individuals who visited our hospital between 2006 and 2012 because of CKD stages 3 to 5 or dialysis treatment were included. Medical records were reviewed for incidence of foot ulceration and major amputation. The time from CKD 3, CKD 4-5, and dialysis treatment until first foot ulceration and first major lower extremity amputation was calculated and analyzed by Kaplan-Meier curves and multivariate Cox proportional hazards model. Diabetes mellitus, peripheral arterial disease, peripheral neuropathy, and foot deformities were included for potential confounding. A total of 669 individuals were included: 539 in CKD 3, 540 in CKD 4-5, and 259 in dialysis treatment (individuals could progress from one group to the next). Unadjusted foot ulcer incidence rates per 1000 patients per year were 12 for CKD 3, 47 for CKD 4-5, and 104 for dialysis (P < .001). In multivariate analyses, the hazard ratio for incidence of foot ulceration was 4.0 (95% confidence interval [CI], 2.6-6.3) in CKD 4-5 and 7.6 (95% CI, 4.8-12.1) in dialysis treatment compared with CKD 3. Hazard ratios for incidence of major amputation were 9.5 (95% CI, 2.1-43.0) and 15 (95% CI, 3.3-71.0), respectively. CKD 4-5 and dialysis treatment are independent risk factors for foot ulceration and major amputation compared with CKD 3. Maximum effort is needed in daily clinical practice to prevent foot ulcers and their devastating consequences in all individuals with CKD 4-5 or dialysis treatment.


Growth stimulating activity of lung extract on lung-colonizing colon 26 clones and its partial characterization.
The effects of lung tissue extract on the cell growth of eight colon 26 tumor clones, four highly and four poorly lung-colonizing clones, were examined in vitro. Addition of lung extract to serum-free medium stimulated the growth of all four of the highly lung-colonizing clones and one of the poorly lung-colonizing clones, but it had minimal effect on the other three poorly lung-colonizing clones. These results indicate that the lung extract contains a growth stimulating activity; it selectively stimulated some of the colon 26 clones including highly lung-colonizing ones. The growth stimulating activity was not dialyzable, was partially destroyed by heating at 56 degrees C or 80 degrees C for 30 min and completely destroyed by trypsin. These results suggest that the activity resides in a protein. Gel filtration chromatography of lung extract on Sephacryl S-200 revealed that the active component was eluted in a molecular weight range of 90,000-120,000.


The predictive validity of atypical neurovegetative depressive symptoms identified by the first principal component in the DUAG trial of moclobemide versus clomipramine.
To investigate to what extent the primary depression subtype atypical depression can predict differential outcome of the mono-amino-oxidase inhibitor (MAO-I) moclobemide and the tricyclic antidepressant clomipramine in the Danish University Antidepressant Group Study (DUAG). In a randomised, double blind trial, a total of 117 patients with major depression were treated over 6 weeks with either 400 mg moclobemide or 150 mg clomipramine. A baseline principal component analysis (PCA) was performed to identify atypical symptoms on the combined depression scales (Hamilton Depression Scale (HAM-D(17)) and the Quantitative Scale for Atypical Depression (QSAD)). The primary outcome scale was the subscale HAM-D(6) which contains the pure items of depression. PCA identified two items with loadings opposite to the other depression items within HAM-D(17) and QSAD, namely increased duration of sleep and increased appetite (atypical neurovegetative symptoms). Patients with a positive score at baseline on these items were classified as having atypical depression. In total 13 patients were classified as having atypical depression. Within this group of patients 8 received clomipramine and 5 patients received moclobemide. At endpoint the moclobemide treated patients had a significantly better response than the clomipramine treated (P=0.036), effect size 1.42, when using HAM-D(6) as outcome. However, in the 104 patients classified as having typical depression clomipramine was superior to moclobemide (P=0.034), effect size 0.47. The number of patients with atypical neurovegetative symptoms was very small and no placebo arm was included. It is very important to screen for atypical depression (increased duration of sleep/increased appetite) in the acute therapy of patients with major depression. Our results add to the body of evidence that monoamine oxidase inhibitors are superior to tricyclic antidepressants in this sub-group of patients.


Catheter ablation of ventricular tachycardia with radiofrequency currents, with special reference to the termination and minor morphologic change of reinduced ventricular tachycardia.
During catheter ablation with radiofrequency (RF) currents, the incidence of the termination of reentrant ventricular tachycardia (VT) during application of RF energy and the morphologic change of the reinduced VT were analyzed. Twenty-five patients (20 men and 5 women, aged 44 +/- 17 years) were studied. After induction of monomorphic sustained VT, the ablation site was determined by endocardial activation mapping, identification of isolated mid-diastolic potential, and pacing during tachycardia. Thirty-six monomorphic VTs were induced in 25 patients and terminated with programmed stimulation. The cycle length was 323 +/- 55 ms and all VTs were entrained with rapid ventricular pacing. The target site was the earliest site of activation of VT in 26 VTs in 16 patients, and the area of slow conduction in 10 VTs in 9 patients. VT was terminated soon after the application of RF currents in 33 VTs in 22 patients at 6.0 +/- 3.1 seconds, and VT was induced immediately after the cessation of RF currents in 11 patients. Of these, 4 patients with idiopathic left ventricular VT had an alternation in the QRS configuration before catheter ablation and required repeat ablation of the other VT morphology. In the other 7 patients, such morphology was not observed before ablation, but was observed in VT induced when the original VT was terminated. Repeated attempts of catheter ablation 2 to 9 times at the remapped site was, however, successful in 7 of 8 VTs.(ABSTRACT TRUNCATED AT 250 WORDS)


Cancer immunotherapy using artificial adjuvant vector cells to deliver NY-ESO-1 antigen to dendritic cells in situ.
NY-ESO-1 is a cancer/testis antigen expressed in various cancer types. However, the induction of NY-ESO-1-specific CTLs through vaccines is somewhat difficult. Thus, we developed a new type of artificial adjuvant vector cell (aAVC-NY-ESO-1) expressing a CD1d-NKT cell ligand complex and a tumor-associated antigen, NY-ESO-1. First, we determined the activation of invariant natural killer T (iNKT) and natural killer (NK) cell responses by aAVC-NY-ESO-1. We then showed that the NY-ESO-1-specific CTL response was successfully elicited through aAVC-NY-ESO-1 therapy. After injection of aAVC-NY-ESO-1, we found that dendritic cells (DCs) in situ expressed high levels of costimulatory molecules and produced interleukn-12 (IL-12), indicating that DCs undergo maturation in vivo. Furthermore, the NY-ESO-1 antigen from aAVC-NY-ESO-1 was delivered to the DCs in vivo, and it was presented on MHC class I molecules. The cross-presentation of the NY-ESO-1 antigen was absent in conventional DC-deficient mice, suggesting a host DC-mediated CTL response. Thus, this strategy helps generate sufficient CD8+ NY-ESO-1-specific CTLs along with iNKT and NK cell activation, resulting in a strong antitumor effect. Furthermore, we established a human DC-transferred NOD/Shi-scid/IL-2γcnull immunodeficient mouse model and showed that the NY-ESO-1 antigen from aAVC-NY-ESO-1 was cross-presented to antigen-specific CTLs through human DCs. Taken together, these data suggest that aAVC-NY-ESO-1 has potential for harnessing innate and adaptive immunity against NY-ESO-1-expressing malignancies.


Down syndrome is associated with altered frequency and functioning of tracheal multiciliated cells, and response to influenza virus infection.
Individuals with Down syndrome (DS) clinically manifest severe respiratory illnesses; however, there is a paucity of data on how DS influences homeostatic physiology of lung airway, and its reactive responses to pulmonary pathogens. We generated well-differentiated ciliated airway epithelia using tracheas from wild-type and Dp(16)1/Yey mice in vitro, and discovered that Dp(16)1/Yey epithelia have significantly lower abundance of ciliated cells, an altered ciliary beating profile, and reduced mucociliary transport. Interestingly, both sets of differentiated epithelia released similar quantities of viral particles after infection with influenza A virus (IAV). However, RNA-sequencing and proteomic analyses revealed an immune hyperreactive phenotype particularly for monocyte-recruiting chemokines in Dp(16)1/Yey epithelia. Importantly, when we challenged mice in vivo with IAV, we observed immune hyper-responsiveness in Dp(16)1/Yey mice, evidenced by higher quantities of lung airway infiltrated monocytes, and elevated levels of pro-inflammatory cytokines in bronchoalveolar lavage fluid. Our findings illuminate mechanisms underlying DS-mediated pathophysiological changes in airway epithelium.


Engineering improved measurement and actuation for nanoscale biophysics.
This commentary profiles the research interests of my recently established research group at The University of Chicago, as well as my own research trajectory and contributions to the field of nanoscale biophysics. I describe here certain open challenges of interest that drive my group's current research efforts, along with my past efforts that have impacted these areas.


Intracellular mechanisms of nitric oxide plus hydrogen peroxide-mediated neutrophil adherence to cultured human endothelial cells.
We investigated signal-transduction in nitric oxide/hydrogen peroxide (NO/H2O2) mediated neutrophil-endothelial adhesion and P-selectin mobilization. Human endothelial monolayers (HUVEC) were exposed to 0.1 mM H2O2 plus an NO donor, 0.5 mM spermine-NONOate, and second message inhibitors and neutrophil adhesion and P-selectin expression measured. Neutrophil adherence induced by NO/H2O2 was blocked by a PKG inhibitor, (KT5823, 0.5 microM), a PKC inhibitor, (Go6976, 10 nM), a calcium chelator, TMB-8 (0.1 mM) and a K+ channel blocker, glibenclamide, (10 microM), but not by a PKA inhibitor, (H-89, 0.1 microM) or a tyrosine kinase inhibitor, (genistein, I microM). P-selectin expression induced by NO/H2O2 was blocked by KT5823 and Gö6976, but not by TMB-8 or glibenclamide. These data demonstrate that NO/ H2O2 promotes neutrophil-endothelial adhesion through PKG, PKC, calcium, and K+ channels, but not PKA or tyrosine kinase. Conversely, P-selectin mobilization requires only PKG and PKC.


Surges in volcanic activity on the Moon about two billion years ago.
The history of mare volcanism critically informs the thermal evolution of the Moon. However, young volcanic eruptions are poorly constrained by remote observations and limited samples, hindering an understanding of mare eruption flux over time. The Chang'e-5 mission returned the youngest lunar basalts thus far, offering a window into the Moon's late-stage evolution. Here, we investigate the mineralogy and geochemistry of 42 olivine and pyroxene crystals from the Chang'e-5 basalts. We find that almost all of them are normally zoned, suggesting limited magma recharge or shallow-level assimilation. Most olivine grains record a short timescale of cooling. Thermal modeling used to estimate the thickness and volume of the volcanism sampled by Chang'e-5 reveals enhanced magmatic flux ~2 billion years ago, suggesting that while overall lunar volcanic activity may decrease over time, episodic eruptions at the final stage could exhibit above average eruptive fluxes, thus revising models of lunar thermal evolution.


Relationships between walking speed, activities and participation in people with chronic stroke in Burundi.
Reduced walking speed because of a stroke may limit activities of daily living (ADLs) and restrict social participation. To describe the level of balance impairment, activity limitations, and participation restrictions and to investigate their relationship with walking speed in Burundians with chronic stroke. This cross-sectional study involved adult stroke survivors. Walking speed, balance, ADLs and social participation were assessed with the 10-meter walk test (10 mWT), the Berg balance scale (BBS), the activity limitation stroke scale and the participation measurement scale, respectively. In order to determine ambulatory independence status, participants were stratified into three walking speed groups (household ambulation, limited ambulation and full-community ambulation), based on the Perry classification. Fifty-eight adults (mean age 52.1 ± 11.4 years) with chronic stroke were included in our study. Most participants had severe balance impairments (median BBS score, 27). Their mean (± standard deviation [SD]) walking speeds, ADL levels and social participation levels were 0.68 ± 0.34 m/s, 50.8% ± 9.3% and 52.8% ± 8.6%, respectively. Walking speed correlated moderately with balance (rho = 0.5, p < 0.001) and strongly with ADL level (r = 0.7, p < 0.001) but not with participation level (r = 0.2, p = 0.25). Using socio-culturally suitable tools, our study showed that walking speed correlates robustly with balance and ADL ability, but not with social participation, in Burundi, a low-income country. Exercises targeting walking speed would be very useful for people with chronic stroke living in low-resource countries, in order to promote their functional independence.


Predictors of lung injury during durvalumab maintenance therapy following concurrent chemoradiotherapy in unresectable locally advanced non-small cell lung carcinoma.
Based on the results of the PACIFIC trial, maintenance with durvalumab has emerged as the standard treatment following concurrent chemoradiotherapy in patients with unresectable locally advanced non-small cell lung carcinoma (NSCLC). However, adverse events attributed to durvalumab, especially lung injuries, including immune-related adverse events, and radiation pneumonitis, are concerning. This study retrospectively investigated the factors related to lung injury in patients receiving the PACIFIC regimen. Patients with unresectable locally advanced NSCLC who received durvalumab maintenance therapy following concurrent chemoradiotherapy at Yokohama City University Medical Centre between July 2018 and March 2022 were included. Clinical data, volume of normal lung receiving 20 or 5 Gy or more (V20 or V5), planning target volume (PTV), and relative lung parenchyma volume in emphysematous lung receiving 20 or 5 Gy or more (RLPV20 or 5; V20 or V5/100-percentage of low-attenuation volume) were evaluated. Performance status (PS), V20, V5, PTV, RLPV20, and RLPV5 were significantly higher in the lung injury group in the univariate analysis. Furthermore, RLPV20 was the most significant factor in the lung injury group in the multivariate analysis comprising PS, PTV, V20, and RLPV20. RLPV20 and RLPV5 are useful in estimating lung inflammation. RLPV20 could be considered the most reliable risk factor for maintenance therapy with durvalumab following concurrent chemoradiotherapy in patients with unresectable locally advanced NSCLC.


Patient Safety Learning Systems: A Systematic Review and Qualitative Synthesis.
A patient safety learning system (sometimes called a critical incident reporting system) refers to structured reporting, collation, and analysis of critical incidents. To inform a provincial working group's recommendations for an Ontario Patient Safety Event Learning System, a systematic review was undertaken to determine design features that would optimize its adoption into the health care system and would inform implementation strategies. The objective of this review was to address two research questions: (a) what are the barriers to and facilitators of successful adoption of a patient safety learning system reported by health professionals and (b) what design components maximize successful adoption and implementation? To answer the first question, we used a published systematic review. To answer the second question, we used scoping study methodology. Common barriers reported in the literature by health care professionals included fear of blame, legal penalties, the perception that incident reporting does not improve patient safety, lack of organizational support, inadequate feedback, lack of knowledge about incident reporting systems, and lack of understanding about what constitutes an error. Common facilitators included a non-accusatory environment, the perception that incident reporting improves safety, clarification of the route of reporting and of how the system uses reports, enhanced feedback, role models (such as managers) using and promoting reporting, legislated protection of those who report, ability to report anonymously, education and training opportunities, and clear guidelines on what to report. Components of a patient safety learning system that increased successful adoption and implementation were emphasis on a blame-free culture that encourages reporting and learning, clear guidelines on how and what to report, making sure the system is user-friendly, organizational development support for data analysis to generate meaningful learning outcomes, and multiple mechanisms to provide feedback through routes to reporters and the wider community (local meetings, email alerts, bulletins, paper contributions, etc.). The design of a patient safety learning system can be optimized by an awareness of the barriers to and facilitators of successful adoption and implementation identified by health care professionals. Evaluation of the effectiveness of a patient safety learning system is needed to refine its design.


The concentration of selected elements in the placenta according to selected sociodemographic factors and their effect on birth mass and birth length of newborns.
The placenta is a remarkable organ which provides critical transport functions between the maternal and fetal circulations during pregnancy. The demand for mineral components increases during the gestational period, therefore, an appropriate intake of minerals, such as calcium, phosphorus, potassium, magnesium, iron, zinc, copper, and manganese, determines the correct growth and development of a fetus. The aim of the study was to assess the concentration of selected elements in the placenta, and to assess the impact of their concentrations on the birth weight and birth length of newborns. The second aim of the study was to assess the influence of selected sociodemographic factors on the concentration of elements in the placenta. The study demonstrated that the age of mothers affected the concentration of Ca and Mn in the placenta, and their habit of tobacco smoking during the gestational period was associated with higher concentrations of Ca, P, K, Mg, Fe, Cu, and Cd in the placental tissue. The results also showed that concentrations of K, Fe, Zn, and Mn in the placental tissue affected birth length. Furthermore, the association was demonstrated between a higher Cd concentration in the placenta (≥ 0.0503 μg/g) and the birth anthropometric parameters of neonates. Smoking during pregnancy and environment pollution are the factors that affects the concentration of elements in the placenta and contributes to their high accumulation in the placenta. Smoking during pregnancy causes an increased concentration of cadmium in the placenta which has negative health effects for the newborn. Women living in a big city or village had a higher concentration of cadmium in their placentas compared to women living in smaller cities. The significant influence of some elements (K, Fe, Zn, Cu and Cd) on the newborn's birth parameters was also demonstrated. The results of our research indicate the importance of the mother's lifestyle in providing the placenta with elements, which affects the growth of the fetus.


MR imaging of children and young adults with classic findings of osteonecrosis on unenhanced MR images: do contrast-enhanced sequences help?
The added value of routine contrast-enhanced MR imaging in children with classic findings of osteonecrosis on unenhanced MR images has not been determined. Our purpose was to determine the added value of routine contrast-enhanced MR sequences for identifying complications of osteonecrosis. Sixty-four patients who underwent 139 contrast-enhanced MR examinations were retrospectively identified. Unenhanced images and subsequently both unenhanced and enhanced images were reviewed in consensus. The location of osteonecrosis and the presence of complicating features (epiphyseal collapse, marrow edema, joint effusion, soft tissue edema) were recorded. Cohen's kappa coefficients (κ) were calculated to assess agreement. A diagnosis of classic osteonecrosis was made in 22.3% of unenhanced examinations and 28.1% of enhanced examinations (κ = 0.734, P < 0.001). Among patients with complicated osteonecrosis, unenhanced images interpreted without and with contrast-enhanced images showed epiphyseal collapse in 51.2% and 42.5% (κ = 0.796, P < 0.001), marrow edema in 50.4% and 46.8% (κ = 0.727, P < 0.001), joint effusion in 44.9% and 51.2% (κ = 0.686, P < 0.001), and soft tissue edema in 12.2% and 10.1% (κ = 0.674, P < 0.001). The high observed agreement between the unenhanced MR images interpreted without and with contrast-enhanced images shows little marginal benefit from the use of routine contrast-enhanced imaging in children and young adults with classic findings of osteonecrosis on unenhanced MR images.


Effects of cyclosporin A and predegeneration on survival and regeneration of peripheral nerve allografts in rabbits.
Axonal regeneration across 64 median nerve grafts in 34 rabbits was studied histologically to determine the optimal conditions for nerve allografting. Axonal regeneration across allografts in cyclosporin A-treated animals was satisfactory, but it occurred more slowly and with more inflammation and fibrosis than in autografts. Without immunosuppression, fresh allografts were rejected. However, in immunocompetent hosts, allografts rendered less immunogenic by predegeneration were not rejected, and axonal regeneration occurred. The combination of cyclosporin A and nerve graft predegeneration produced the most substantial axonal regeneration, comparable to autografts. The observations suggest that nerve allograft survival may be optimally effected by cyclosporin A treatment coupled with reduction in the immunogenicity of the grafts, such as by predegeneration.


Plant-derived abrin-a induces apoptosis in cultured leukemic cell lines by different mechanisms.
Abrin-a consists of A-chain with N-glycosidase activity, which inhibits protein synthesis, and lectin-like B-chain responsible for binding with cell-surface receptors and penetrating of abrin-a molecule into the cells. As a lectin component, the B-chain can also participate in cell signal transduction. It has been reported that abrin induces apoptosis, but the molecular mechanism(s) of this induction have been obscure and several alternative variants have been discussed. The present study demonstrates that abrin-a induces apoptosis in human cultured cell lines, derived from acute lymphoblastic leukemia (ALL) (Jurkat, CCRF-CEM, MOLT-4, HPB-ALL). The apoptosis was estimated by: phosphatidylserine (PSer) exposure at the cell surface, activation of caspase cascade, and DNA fragmentation. The penetrating of abrin-a into the cells was detected by fluorescent confocal microscopy, using fluorescein isothiocyanate (FITC) as a fluorescent marker. It was established that the effect of abrin-a on the apoptosis induction in leukemic cells was dose- and time-dependent. The process was initiated 1 h after abrin-a application (before its penetrating into the cells) and was characterized with PSer translocation from the inner to the outer monolayer of plasma membrane, caspase activation on the first to second hour after beginning of treatment, with maximum on the third to fourth hour, and DNA fragmentation on the fourth to sixth hour, depending of the cell line. The exposure of PSer on the cell surface was detected in Jurkat, CCRF-CEM, and MOLT-4 cells. In HPB-ALL, no significant changes in PSer exposure on the cell surface was observed. Activation of caspase-3, -8, and -9 was detected in Jurkat, MOLT-4, and HPB-ALL. Surprisingly, the activity of caspase-3 increased on the first hour after beginning of treatment, while the activity of caspase-8 and -9 began to increase on the second hour. In CCRF-CEM, activation of caspases was not measured, but the apoptosis progressed to DNA fragmentation in a dose- and time-dependent manner. DNA fragmentation was also detected in Jurkat, but not in MOLT-4 and HPB-ALL cells. It seems that the mechanisms of abrin-a-induced apoptosis are different and the progress of apoptosis depends of the cell line. There was a very good positive correlation between the agglutinating activity of abrin-a and development of apoptosis to DNA fragmentation. The time-dependent effects of abrin-a on apoptosis as well as its time-dependent penetration into the cells suggest that the B-chain probably triggers the apoptosis, while the A-chain and breakage of the disulfide bond are responsible for its progress.


Antiepileptogenic action of 7-chlorokynurenic acid on amygdala kindling of rats.
To investigate the role of strychnine-insensitive glycine receptors in epilepsy, we studied the effects of 7-chlorokynurenic acid (7-CK), a selective strychnine-insensitive glycine receptor antagonist, on amygdala kindling development and previously amygdala-kindled seizures in rats. ICV administration of 7-CK (10 or 20 micrograms) suppressed amygdala kindling development, according to the motor seizure stage and afterdischarge development, in a dose-dependent manner. However, 7-CK had no significant effect on previously kindled seizures at either of these doses nor did 20 micrograms at any time (15 min, 30 min, 2 h, and 24 h) after injection studied. These results demonstrate that this selective strychnine-insensitive glycine receptor antagonist has antiepileptogenic activity and suggest a role for the glycine receptors in the contribution of the NMDA receptor complex to epileptogenic events.


Investing in green and white biotech.
A substantial increase in political and financial investment that aligns plant and industrial biotech will pay dividends for sustainable energy and materials production.


MRI features of sinonasal tract angiofibroma/juvenile nasopharyngeal angiofibroma: Case series and systematic review.
To comprehensively summarize the radiological characteristics of sinonasal tract angiofibroma (STA) (commonly known as juvenile nasopharyngeal angiofibroma). Forty-four lesions from 41 cases provided by 33 study articles identified through a systematic review and 13 lesions from 13 cases from our institution associated with patients with STA who underwent MRI were included in the review study, carried out by two board-certified experienced radiologists. The study participants were all male patients with a mean age of 15.6 years at the time of diagnosis. All of them presented with nasal cavity lesions (100%), predominantly in the nasopharynx (98.2%). The sphenopalatine foramen/pterygopalatine fossa was involved in 76.0%, and compressive shift of the posterolateral wall of the maxillary sinus was present in more than half (57.9%). T2-weighted imaging signal intensity was heterogeneous with mixed high and iso intensities as compared to skeletal muscle (100%). T1-weighted imaging showed partial high signal intensity in 61.1% of the cases. Flow void and intense enhancement were present in almost all cases. Cystic/nonenhancement changes on contrast-enhanced MRI were relatively common (40.8%). The mean apparent diffusion coefficient value (2.07 × 10-3 mm2 /second) and some quantitative dynamic contrast-enhanced MRI parameters were high. There was a significant difference in the frequency of residual/recurrent lesions based on the presence of MRI findings of skull base invasion (p = .017) and intracranial extension (p = .003). We summarized the MRI findings of STA that can facilitate timely diagnosis and appropriate management.


Pathogenic mutations in the glycosylphosphatidylinositol signal peptide of PrP modulate its topology in neuroblastoma cells.
Point mutations M232R (PrP(232R)), M232T (PrP(232T)), and P238S (PrP(238S)) in the glycosylphosphatidylinositol signal peptide (GPI-SP) of the prion protein (PrP(C)) segregate with familial Creutzfeldt-Jakob disease (CJD). However, the mechanism by which these mutations induce cytotoxicity is unclear since the GPI-SP is replaced by a GPI anchor within 5 min of PrP synthesis and translocation into the endoplasmic reticulum (ER). To examine if mutations in this region interfere with translocation of nascent PrP into the ER or anchor addition, the metabolism of PrP(232R) and PrP(232T) was investigated in transfected human neuroblastoma cells. In this report, we demonstrate that PrP mutations M232R and M232T do not interfere with GPI anchor addition. Instead, these mutations increase the stability and transport of GPI-SP mediated post-translationally translocated PrP to the plasma membrane, where it is linked to the lipid bilayer in a potentially neurotoxic C-transmembrane ((Ctm)PrP) orientation. Furthermore, we demonstrate that the GPI-SP of PrP functions as an efficient co-translational and inefficient post-translational ER translocation signal when tagged to an unrelated protein, underscoring the functional versatility of this peptide. These data uncover an alternate pathway of ER translocation for nascent PrP, and provide information on the possible mechanism(s) of neurotoxicity by mutations in the GPI-SP.


New uracil analogs as downregulators of ABC transporters in 5-fluorouracil-resistant human leukemia HL-60 cell line.
Overexpression of ATP-binding cassette (ABC) transporters causing multidrug resistance (MDR) in cancer cells is one of the major obstacles in cancer chemotherapy. The 5-FU resistant subclone (HL-60/5FU) of the human HL-60 promyelocytic leukemia cell line was selected by the conventional method of continuous exposure of the cells to the drug up to 0.08 mmol/L concentration. HL-60/5FU cells exhibited six-fold enhanced resistance to 5-FU than HL-60 cells. RT-PCR and ELISA assay showed significant overexpression of MDR-related ABC transporters, ABCB1, ABCG2 but especially ABCC1 in the HL-60/5FU as compared with the parental cell line. Three novel synthetic 5-methylidenedihydrouracil analogs, U-236, U-332 and U-359, selected as highly cytotoxic for HL-60 cells in MTT test, showed similar cytotoxicity in the resistant cell line. When co-incubated with 5-FU, these analogs were found to down-regulate the expression of all three transporters. However, the most pronounced effect was caused by U-332 which almost completely abolished ABCC1 expression in the resistant HL-60/5FU cells. Additionally, U-332 inhibited the activity of ATPase, an enzyme which catalyzes hydrolysis of ATP, providing energy to efflux drugs from the cells through the cellular membranes. Taken together, the obtained data suggest that acquired 5-FU resistance in HL-60/5FU cells results from overexpression of ABCC1 and that targeting ABCC1 expression could be a potential approach to re-sensitize resistant leukemia cells to 5-FU. The synthetic uracil analog U-332, which can potently down-regulate ABC transporter expression and therefore disturb drug efflux, can be considered an efficient ABCC1 regulator in cancer cells.


[Dapsone inhibition of the bactericidal action of rifampicin on Mycobacterium leprae in mice].
In the experimental infection of mice by Mycobacterium leprae, the bactericidal effect of 4 weekly doses of rifampicin (RMP) is completely suppressed if this administration is preceded by a daily treatment of dapsone (DDS) during one month then continued in conjunction with rifampicin. The application of this methodology: the delayed adding of rifampicin clearly shows the bacillary persistence induced by dapsone (DDS). The rifampicin appears to be less effective on Mycobacterium leprae when its metabolism is inhibited either by the action of a drug such as dapsone (DDS), or spontaneously. The highlighting of this late-appearing antagonism between rifampicin and dapsone in mice, should not at present lead to the questioning of the therapeutic procedures recommended by the WHO, because of the limits of this experimental model, namely the small size of bacillary populations studied over relatively short periods of time.


Amine oxidase substrates for impaired glucose tolerance correction.
Amine oxidases are widely distributed from microorganisms to vertebrates and produce hydrogen peroxide plus aldehyde when catabolizing endogenous or xenobiotic amines. Novel roles have been attributed to several members of the amine oxidase families, which cannot be anymore considered as simple amine scavengers. Semicarbazide-sensitive amine oxidase (SSAO) is abundantly expressed in mammalian endothelial, smooth muscle, and fat cells, and plays a role in lymphocyte adhesion to vascular wall, arterial fiber elastic maturation, and glucose transport, respectively. This latter role was studied in detail and the perspectives of insulin-like actions of amine oxidase substrates are discussed in the present review. Independent studies have demonstrated that SSAO substrates and monoamine oxidase substrates mimic diverse insulin effects in adipocytes: glucose transport activation, lipogenesis stimulation and lipolysis inhibition. These substrates also stimulate in vitro adipogenesis. Acute in vivo administration of amine oxidase substrates improves glucose tolerance in rats, mice and rabbits, while chronic treatments with benzylamine plus vanadate exert an antihyperglycaemic effect in diabetic rats. Dietary supplementations with methylamine, benzylamine or tyramine have been proven to influence metabolic control in rodents by increasing glucose tolerance or decreasing lipid mobilisation, without noticeable changes in the plasma markers of lipid peroxidation or protein glycation, despite adverse effects on vasculature. Thus, the ingested amines are not totally metabolized at the intestinal level and can act on adipose and vascular tissues. In regard with this influence on metabolic control, more attention must be paid to the composition or supplementation in amines in foods and nutraceutics.


A glycolytic shift in Schwann cells supports injured axons.
Axon degeneration is a hallmark of many neurodegenerative disorders. The current assumption is that the decision of injured axons to degenerate is cell-autonomously regulated. Here we show that Schwann cells (SCs), the glia of the peripheral nervous system, protect injured axons by virtue of a dramatic glycolytic upregulation that arises in SCs as an inherent adaptation to axon injury. This glycolytic response, paired with enhanced axon-glia metabolic coupling, supports the survival of axons. The glycolytic shift in SCs is largely driven by the metabolic signaling hub, mammalian target of rapamycin complex 1, and the downstream transcription factors hypoxia-inducible factor 1-alpha and c-Myc, which together promote glycolytic gene expression. The manipulation of glial glycolytic activity through this pathway enabled us to accelerate or delay the degeneration of perturbed axons in acute and subacute rodent axon degeneration models. Thus, we demonstrate a non-cell-autonomous metabolic mechanism that controls the fate of injured axons.


Effect of pattern luminance profile on the pattern ERG in man and pigeon.
Pattern electroretinograms (PERGs) have been recorded in man and pigeon using phase reversing patterns. Studies were made in both species of the effect of grating spatial frequency, grating profile (sine or square) or the size of the squares of a checkerboard on the amplitude of the responses. The results obtained in the two species were similar. In general, the ratio of the amplitudes of the sine wave:square wave responses is that predicted by the Fourier fundamentals of the pattern, and is thus not determined by changes in local luminance or contrast as it is normally defined. Checks however gave larger responses than sine or square wave profile bars matched to the Fourier fundamental on the diagonal. The results are not explicable in terms of any single stimulus parameter and suggest that the PERG generator has a degree of center/surround organisation similar to retinal ganglion cells. It is however argued that, because of the known physiological properties, generators cannot be unequivocally localised by varying the stimulus or comparing retinal, cortical and perceptual response dynamics.


Regulatable acetylcholine-producing fibroblasts enhance cognitive performance.
Regulatable gene therapy systems provide a method to alter neurotransmitter levels in vivo. We developed a rodent fibroblast cell line expressing the choline acetyltransferase (ChAT) cDNA that is silenced by doxycycline (DOX) administration. The ability of the cell line to improve cognition was tested by grafting after cholinergic lesions. Ibotenic acid was injected bilaterally into the nucleus basalis of rats, which were distributed into three groups. One group received no treatment, while the second group received cortical transplants (Graft). The third group received identical grafts but was treated with DOX to turn off ChAT expression (Graft/DOX). An unlesioned group served as control. Water maze acquisition was significantly better in the Graft group compared to the Graft/DOX group, an effect also seen in the retention and spatial probe trials. However, cognitive enhancement was restricted to spatial tasks, as inhibitory avoidance or open-field activity measures were unchanged. Molecular and biochemical analyses confirmed that DOX regulated transgene transcription and ACh levels. This study demonstrates that regulatable gene therapy has therapeutic value for single-gene disorders and also provides a mechanism to deliver small molecules in a spatiotemporal pattern to delineate the role of these compounds in discrete behavioral tasks.


Secretion of heterologous proteins in Bacillus subtilis can be improved by engineering cell components affecting post-translocational protein folding and degradation.
To explore the potential to enhance secretion of heterologous proteins in Bacillus subtilis by engineering cell factors affecting extracytoplasmic protein folding and degradation. Bottleneck components affecting the extracytoplasmic phase of protein secretion were genetically engineered and their effects on the secretion of 11 industrially interesting heterologous proteins were studied by Western blotting and enzymatic assays. Overproduction of PrsA lipoprotein enhanced the secretion of alpha-amylase of Bacillus stearothermophilus (fourfold) and pneumolysin (1.5-fold). Increasing the net negative charge of the cell wall because of lack of the d-alanine substitution of anionic cell wall polymers enhanced the secretion of pneumolysin c. 1.5-fold. Decreasing the level of HtrA-type quality control proteases caused harmful effects on growth and did not enhance secretion. Pertussis toxin subunit, S1 was found to be a substrate for HtrA-type proteases and its secretion was dependent on these proteases. Secretion of heterologous proteins can be enhanced by engineering components involved in late stages of secretion in a protein-dependent manner. The study revealed both possibilities and limitations of modulating the post-translocational phase of secretion as a means to improve the yield of heterologous proteins.


Estimation of radon exhalation rate, natural radioactivity and radiation doses in fly ash samples from Durgapur thermal power plant, West Bengal, India.
Coal and its by products often contain significant amounts of radionuclides, including uranium which is the ultimate source of the radioactive gas radon. Burning of coal and the subsequent emission to the atmosphere cause the re-distribution of toxic trace elements in the environment. Due to considerable economic and environmental importance and diverse uses, the collected fly ash has become a subject of worldwide interest in recent years. In the present study, radon exhalation rate and the activity concentration of (238)U, (232)Th and (40)K radionuclides in fly ash samples from Durgapur thermal power plant (WB) have been measured by "Sealed Can technique" using LR-115 type II detectors and a low level NaI (Tl) based gamma ray spectrometer, respectively. Radon exhalation rate varied from 360.0 to 470.0 mBq m(-2)h(-1) with an average value of 406.8 mBq m(-2)h(-1). Activity concentrations of (238)U ranged from 84.8 to 126.4 Bq kg(-1) with an average value of 99.3Bqkg(-1), (232)Th ranged from 98.1 to 140.5 Bq kg(-1) with an average value of 112.9 Bq kg(-1) and (40)K ranged from 267.1 to 364.9 Bq kg(-1) with an average value of 308.9 Bq kg(-1). Radium equivalent activity obtained from activity concentrations is found to vary from 256.5 to 352.8 Bq kg(-1) with an average value of 282.5 Bq kg(-1). Absorbed gamma dose rates due to the presence of (238)U, (232)Th and (40)K in fly ash samples vary in the range 115.3-158.5 nGy h(-1) with an average value of 126.4 nGy h(-1). While the external annual effective dose rate varies from 0.14 to 0.19 mSv y(-1) with an average value of 0.15 mSv y(-1), effective dose equivalent estimated from exhalation rate varies from 42.5 to 55.2 microSv y(-1) with an average value of 47.8 microSv y(-1). Values of external hazard index H(ex) for the fly ash samples studied in this work range from 0.69 to 0.96 with a mean value of 0.77.


CT-defined pectoralis muscle mass and muscle density are associated with mortality in acute pulmonary embolism. A multicenter analysis.
Computed tomography (CT) defined muscle mass can be used as a surrogate parameter for sarcopenia. The present study used thoracic CT to assess pectoralis muscle area and density as an imaging biomarker for prognosis of 30-day mortality in patients with acute pulmonary embolism (PE) METHODS: The clinical database was retrospectively screened for patients with thoracic CT in 3 centers. Pectoralis musculature was measured on axial slices of the thoracic CT at the level of T4 of contrast enhanced pulmonary angiography CT. Skeletal muscle area (SMA), skeletal muscle index (SMI), muscle density and gauge were calculated. Overall, 981 patients (440 female, 44.9%) with a mean age of 63.5 ± 15.9 years were included into the study and 144 patients (14.6%) died within the 30-days period. Every pectoral muscle value was higher in survivors compared to non-survivors (exemplarily for SMI 9.9 ± 3.5 cm2/m2 versus 7.8 ± 2.6 cm2/m2, p < 0.001). Moreover, 91 patients were defined as hemodynamically instable (9.3%). Comparable, every pectoral muscle parameter was higher in patients with hemodynamically stable course compared to instable course. Different muscle variables are related to 30-day mortality: SMA, OR = 0.94 (95%CI= (0.92; 0.96), p < 0.001); SMI, OR = 0.78 (95%CI= (0.72; 0.84), p < 0.001); muscle density, OR = 0.96 (95%CI = (0.94; 0.97), p < 0.001); muscle gauge OR = 0.96 (95%CI = (0.94; 0.99), p < 0.001). SMI and muscle density were independently associated with 30-days mortality: SMI, OR = 0.81 (95%CI = (0.75; 0.88), p < 0.001); muscle density: OR = 0.96 (95%CI= (0.95; 0.98), p < 0.001). Parameters of the pectoralis musculature are associated with 30-day mortality in patients with acute PE. These findings should lead to an independent validation study and ultimately to the inclusion into clinical routine as a prognostic factor.


Continuum modeling of non-conservative fluid membrane for simulating long-term cell dynamics.
Living cells actively deform and move by their force generations in three-dimensional (3D) space. These 3D cell dynamics occur over a long-term time scale, ranging from tens of minutes to days. On such a time scale, turnover of cell membrane constituents due to endocytosis and exocytosis cannot be ignored, i.e., the surface membrane dynamically deforms without mass conservation. Although membrane turnover is essential for large deformation of cells, there is no computational framework yet to simulate long-term cell dynamics with a non-conservative fluidic membrane. In this paper, we proposed a computational framework for simulating the long-term dynamics of a cell membrane in 3D space. For this purpose, in the proposed framework, the cell surface membrane is treated as a viscous fluid membrane without mass conservation. Cell shape is discretized by a triangular mesh, and its dynamics are expressed by effective energy and dissipation function. The mesh structure, distorted by membrane motion, is dynamically optimized by introducing a modified dynamic remeshing method. To validate the proposed framework, numerical simulations were performed, showing that the membrane flow is reproduced in a physically consistent manner and that the artificial effects of the remeshing method were negligible. To further demonstrate the applicability of the proposed framework, numerical simulations of cell migration induced by a mechanism similar to the Marangoni effect, i.e., the polarized surface tension actively generated by the cell, were performed. The observed cell behaviors agreed with existing analytical solutions, indicating that the proposed computational framework can quantitatively reproduce long-term active cell dynamics with membrane turnover. Based on the simple description of cell membrane dynamics, this framework provides a useful basis for analyzing various cell shaping and movement.


CosTaL: an accurate and scalable graph-based clustering algorithm for high-dimensional single-cell data analysis.
With the aim of analyzing large-sized multidimensional single-cell datasets, we are describing a method for Cosine-based Tanimoto similarity-refined graph for community detection using Leiden's algorithm (CosTaL). As a graph-based clustering method, CosTaL transforms the cells with high-dimensional features into a weighted k-nearest-neighbor (kNN) graph. The cells are represented by the vertices of the graph, while an edge between two vertices in the graph represents the close relatedness between the two cells. Specifically, CosTaL builds an exact kNN graph using cosine similarity and uses the Tanimoto coefficient as the refining strategy to re-weight the edges in order to improve the effectiveness of clustering. We demonstrate that CosTaL generally achieves equivalent or higher effectiveness scores on seven benchmark cytometry datasets and six single-cell RNA-sequencing datasets using six different evaluation metrics, compared with other state-of-the-art graph-based clustering methods, including PhenoGraph, Scanpy and PARC. As indicated by the combined evaluation metrics, Costal has high efficiency with small datasets and acceptable scalability for large datasets, which is beneficial for large-scale analysis.


Validation of a central review board of staging prior to surgery for non-small-cell lung cancer--impact on prognosis: a multicenter study.
In non-small-cell lung cancer (NSCLC), the evaluation of anatomic tumor extension [tumor, node, metastasis (TNM) stage] is indispensable for the exchange of scientific information or determining prognosis. To quantify changes in TNM stages (numerical migration) and survival (prognostic migration) resulting from the application of classificatory certainty criteria to patients with NSCLC who had undergone surgical treatment. The study population included 1,844 patients registered by the Bronchogenic Carcinoma Cooperative Group of the Spanish Society of Pneumology and Thoracic Surgery (GCCB-S). For every patient, two evaluations were made of each component of the TNM classification: an initial classification, defined by a local representative, and a confirmed classification resulting from the application of stricter classificatory criteria by the GCCB-S Central Review Board. The results revealed scant numerical migration in the cT category (11.5% of the study population) and a general tendency toward a downstaging. In contrast, the initial cN1 category experienced a complete numerical migration and the initial cN2 category a very large numerical migration (from 200 to 22 cases). In the small group of patients for whom there was a classificatory change in cT (n = 212), the migration for the cT2 category was accompanied by a less favorable prognosis (p = 0.039, log-rank test). However, the migration of this small subset of patients did not affect the general prognosis of the study population for cT2. In cN2, the 3-year survival rate migrated from 0.42 to 0.29. Numerical migration resulting from the application of stricter classificatory criteria was relevant, but had little, although unfavorable, global prognostic impact.


Interleukin 2 receptor subunit beta as a novel hub gene plays a potential role in the immune microenvironment of abdominal aortic aneurysms.
Abdominal aortic aneurysm (AAA) is potentially life threatening and characterized by immune-inflammatory cell infiltration and extracellular matrix degradation. Currently, pharmacotherapy mainly aims to control risk factors without reversion of the dilated aorta. This study analyzed the immune-inflammatory response and identified the immune-related hub genes of AAA. Gene Expression Omnibus datasets (GSE57691, GSE47472 and GSE7084) were downloaded. After identification of GSE57691 differentially expressed genes (DEGs), weighted gene co-expression network analysis of the DEGs was performed. Through enrichment analysis of each module and screening in Immunology Database and Analysis Portal, immune-related hub genes were identified via protein-protein interaction (PPI) network construction and lasso regression. CIBERSORT was utilized to analyze AAA immune infiltration. The correlations between the immune-related hub genes and infiltrating immune cells were investigated. Receiver operating characteristic (ROC) curve analysis was performed to determine immune-related hub gene cutoff values, which were validated in GSE47472 and GSE7084. In GSE57691, 1,018 DEGs were identified. Five modules were identified in the co-expression network. The blue and green modules were found to be related to immune-inflammatory responses, and 61 immune-related genes were identified. PPI and lasso regression analyses identified FOS, IL-6 and IL2RB as AAA immune-related hub genes. CIBERSORT analysis indicated significantly increased infiltration of naive B cells, memory activated CD4 T cells, follicular helper T cells, monocytes and M1 macrophages and significantly decreased infiltration of M2 macrophages in AAA compared with normal samples. IL2RB was more strongly associated with immune infiltration in AAA than were FOS and IL6. The IL2RB area under the ROC curve (AUC) value was > 0.9 in both the training and validation set, demonstrating its strong, stable diagnostic value in AAA. AAA and normal samples had different immune infiltration statuses. IL2RB was identified as an immune-related hub gene and a potential hub gene with significant diagnostic value in AAA.


Polymorphisms in the interleukin-4 and interleukin-4 receptor alpha chain genes confer susceptibility to asthma and atopy in a Caucasian population.
IL-4 by binding to its receptor (IL-4R) is essential for the development of airway inflammation present in asthma, through the induction of IgE synthesis in B cells and differentiation of T cells to a Th2 phenotype. To investigate the role of four common polymorphisms in the IL-4 (IL4-34CT and IL4-589CT) and IL-4Ralpha chain (IL4RAI50V and IL4RAQ576R) genes in conferring susceptibility to the development of atopy and/or asthma. Two polymorphisms in the IL-4 gene promoter, IL4-34CT and IL4-589CT, and two polymorphisms in the IL-4Ralpha chain gene, IL4RAI50V and IL4RAQ576R, have been genotyped using PCR-based methods in 341 asthmatic families and in 184 non-asthmatic adults recruited from the south of England. Case-control analysis did not reveal differences in the distribution of the four polymorphisms between asthmatics and controls. However, the transmission disequilibrium test showed that the IL4-589 T allele was preferentially transmitted to asthmatic children (P=0.036) and that the IL4RAQ576 was preferentially transmitted to children with atopic asthma (P=0.018). Haplotype analysis showed a strong association between the IL4-34T/-589T haplotype and asthma per se (P=0.041), and a strong association between the IL4RA I50/Q576 haplotype and atopic asthma (P=0.006). Our data suggest that polymorphisms in the IL-4 and IL-4Ralpha chain genes might play a role both conferring susceptibility to and modulating severity of atopy and asthma.


Automatic diagnosis of pneumothorax with M-mode ultrasound images based on D-MPL.
To address the difficulties of M-mode ultrasound images classification in pneumothorax diagnosis and the shortcomings of existing neural network algorithms in this field, we proposed an M-mode ultrasound images classification model based on Disturbed Meta-Pseudo-Labels (D-MPL). An M-mode ultrasound image augmentation system was designed to make the model more robust and generalizable. In D-MPL, teacher-generated pseudo-labeling was first taught to students through a soft mask, and additional disturbance data were added to the teacher network. As the loss of the teacher network continues to decline, disturbance data were injected to improve the generalization of the model to cope with image differences across patients in clinical settings. We compared the proposed model with four commonly used models, including MPL, EfficientnetB2, Inception V3, and Resnet101, in order to confirm its efficacy. Our model has an average specificity of 98.28%, sensitivity of 98.22%, F1-score of 98.23%, and AUC of 98.10%, according to the experiment findings, and its comprehensive performance is better than the above four models. The results demonstrated our model's superiority over the competition and its greater. The model proposed in this study is expected to assist doctors in the diagnosis of pneumothorax as an auxiliary mean.


Gastro-protective treatment in patients using NSAIDs. Development of appropriateness criteria by a multidisciplinary expert panel.
To refine the appropriate indications for gastro-protective treatment in patients using non-steroidal anti-inflammatory drugs (NSAIDs). Using the RAND Appropriateness Method, a multidisciplinary expert panel was asked to rate the appropriateness of gastro-protection for 4608 different cases. Logistic regression was used to construct a decision framework to identify patients for whom gastro-protective medication should be considered. Complete consensus existed on the appropriate use of gastro-protection in patients with a history of (un)complicated peptic ulcer. For other patients. agreement was found for 39% over 1536 cases. Logistic regression demonstrated strong consistency of the panel ratings (Hosmer Lemeshow coefficient 0.92), allowing the development of a comprehensive decision support model. Using the RAND Appropriateness Method, we were able to develop a clear and internally consistent decision framework for the appropriate use of gastro-protection in patients taking NSAIDs. The validity of this model should be tested in further studies and practice.


High-dose cyclophosphamide and adriamycin with DTIC maintenance for metastatic soft tissue sarcomas.
Intensive chemotherapy with high-dose cyclophosphamide and adriamycin with DTIC maintenance was given to 12 patients with metastatic soft tissue sarcomas. A partial response rate of 25% was seen; this is no better than can be achieved with single-agent therapy. Because of substantial toxicity without improved efficacy, the trial of high dose therapy was halted.


The C825T GNB3 polymorphism, independent of blood pressure, predicts cerebrovascular risk at a population level.
The role of C825T polymorphism of the candidate GNB3 gene in predicting cerebrovascular outcome has been poorly explored in longitudinal setting at a population level. In an epidemiological setting, 1,678 men and women from general population were genotyped for C825T polymorphism of GNB3 gene and follow-up for 10 years to detect nonfatal and fatal cerebrovascular events (CE). Established cerebrovascular risk factors were used to adjust the multivariate Cox analysis for confounders. Seventy-three nonfatal and 30 fatal CE were recorded. Incidence of CE was higher in TT than in C-carriers (fatal: 2.6 vs. 1.7%, P < 0.03; nonfatal: 7.8 vs. 3.9%, P < 0.03; fatal recurrences: 1.6 vs. 0.6%, P < 0.03). In Cox analysis, the TT genotype predicted nonfatal (hazard ratio 1.99, 95% confidence interval 1.05-3.79, P = 0.03), fatal (2.91, 1.05-8.12, P = 0.04), and fatal recurrent CE (6.82, 1.50-31.1, P = 0.02) also after adjustment for age, gender, systolic and diastolic blood pressure, body adiposity, atherogenetic blood lipids, serum uric acid, diabetes, calories, caffeine and ethanol intake, and coronary events at baseline. Further adjustment for historical CE made the association between TT genotype and incident fatal CE nonsignificant (hazard ratio 2.72, 95% confidence interval 0.96-7.22, P = 0.06). The TT genotype of GNB3 gene predicts incident CE independent of blood pressure and other established risk factors at a population level. Further studies are needed to clarify the nature and pathways of this association.


The importance of the tissue microenvironment in hairy cell leukemia.
Hairy cell leukemia (HCL) cells engage in complex cellular and molecular interactions with accessory cells, matrix proteins, and various cytokines in the bone marrow and spleen, collectively referred to as the tissue microenvironment. Chemokine receptors and adhesion molecules are critical players for homing and retention within these microenvironments. Engagement of B cell antigen receptors and CD40 on HCL cells promote survival and proliferation. In this chapter, we summarize the current knowledge about the cellular and molecular interactions between HCL cells and their supportive tissue microenvironment, and provide insight into new therapeutic approaches targeting B cell receptor signaling in HCL.


Application of WeChat-assisted peri-operative care in children with congenital megacolon.
This study explored the clinical effects of WeChat-based peri-operative care on parents of children with congenital megacolon. Participants were randomly divided into WeChat group and telephone group. This study explored parents' knowledge of the care of children with megacolon, the follow-up rate of children, post-operative defaecation function and complications. WeChat group scored better in nursing knowledge than telephone group, and the difference was statistically significant. The lost follow-up rate in WeChat group was lower than that in telephone group, and the difference was statistically significant. Post-operative defaecation was also better in the WeChat group than in the phone group. Most complications in the phone group were significantly higher than those in the WeChat group. Peri-operative care for parents of children with megacolon through WeChat can effectively enhance the level of parental care knowledge, improve defaecation, reduce the occurrence of certain complications and reduce lost follow-up.


Clinical characteristics and comorbidities associated with SARS-CoV-2 breakthrough infection in the University of California Healthcare Systems.
To evaluate the degree to which clinical comorbidities or combinations of comorbidities are associated with SARS-CoV-2 breakthrough infection. A breakthrough infection was defined as a positive test at least 14 days after a full vaccination regimen. Logistic regression was used to calculate aORs, which were adjusted for age, sex, and race information. A total of 110,380 patients from the UC CORDS database were included. After adjustment, stage 5 CKD due to hypertension (aOR: 7.33; 95% CI: 4.86-10.69; p<.001; power=1) displayed higher odds of infection than any other comorbidity. Lung transplantation history (aOR: 4.79; 95% CI: 3.25-6.82; p<.001; power= 1), coronary atherosclerosis (aOR: 2.12; 95% CI: 1.77-2.52; p<.001; power=1), and vitamin D deficiency (aOR: 1.87; 95% CI: 1.69-2.06; p<.001; power=1) were significantly correlated to breakthrough infection. Patients with obesity in addition to essential hypertension (aOR: 1.74; 95% CI: 1.51-2.01; p<.001; power=1) and anemia (aOR: 1.80; 95% CI: 1.47-2.19; p<.001; power=1) were at additional risk of breakthrough infection compared to those with essential hypertension and anemia alone. Further measures should be taken to prevent breakthrough infection for individuals with these conditions, such as acquiring additional doses of the SARS-CoV-2 vaccine to boost immunity.


Intra-individual comparison of human nasal chondrocytes and debrided knee chondrocytes: Relevance for engineering autologous cartilage grafts.
Implantation of autologous chondrocytes for cartilage repair requires harvesting of undamaged cartilage, implying an additional joint arthroscopy surgery and further damage to the articular surface. As alternative possible cell sources, in this study we assessed the proliferation and chondrogenic capacity of debrided Knee Chondrocytes (dKC) and Nasal Chondrocytes (NC) collected from the same patients. Matched NC and dKC pairs from 13 patients enrolled in two clinical studies (NCT01605201 and NCT026739059) were expanded in monolayer and then chondro-differentiated in 3D collagenous scaffolds in medium with or without Transforming Growth Factor beta 1 (TGFβ1). Cell proliferation and amount of cartilage matrix production by these two cell types were assessed. dKC exhibited an inferior proliferation rate than NC, and a lower capacity to chondro-differentiate. Resulting dKC-grafts contained lower amounts of cartilage specific matrix components glycosaminoglycans and type II collagen. The cartilage forming capacity of dKC did not significantly correlate with specific clinical parameters and was only partially improved by medium supplemention with TGFβ1. dKC exhibit a reproducibly poor capacity to engineer cartilage grafts. Our in vitro data suggest that NC would be a better suitable cell source for the generation of autologous cartilage grafts.


Symptomatic HIV infection of the CNS in a patient without clinical evidence of immune deficiency.
Major depression with psychotic features, dementia, and focal neurologic abnormalities appeared in a Haitian man without AIDS or other syndromes of immune compromise. Neurologic evaluation, including brain biopsy, was nondiagnostic, but CSF culture revealed human immunodeficiency virus (HIV).


New method of remnant closure during distal pancreatectomy.
Pancreatic fistula following distal pancreatectomies still remains a relevant problem. The present study describes our first series with a new method of pancreatic remnant closure. A free fascia-peritoneum graft - harvested from the internal rectus sheet - was fixed onto the pancreatic stump by one circular stitch. The method was applied in 18 cases. The postoperative hospital stay was 8 days in average. No clinically relevant postoperative pancreatic fistula (CR-POPF) developed. The morbidity rate was 39%, mostly Clavien-Dindo Grade II types. There was no reoperation or mortality. The first series showed advantageous results with our method. Certainly, further studies are needed for the evaluation of this new and promising technique.


Alzheimer's disease and depression: preclinical comorbidity effects on cognitive functioning.
Both Alzheimer's disease (AD) and depression (D) are prevalent disorders in old age and may co-occur in the same individual. The present study examined whether a diagnosis of D in AD has negative effects on cognitive functioning in the preclinical stage of the diseases, as well as at the time when the diagnoses were rendered. Population-based samples of 13 individuals with incident AD and D, 109 incident AD cases without D, and 179 normal older adults were followed over a three-year period. The groups were compared preclinically and at the time of diagnosis on global cognitive functioning using the MMSE total and the specific item scores, as well as the occurrence of depressive symptoms. As expected, there were clear AD-related deficits preclinically, which were exacerbated at follow-up. In addition, there were D-related deficits on three MMSE items (i.e., following commands, reading, and writing). The poorer performance on the three MMSE items was linked to an elevation of depressive symptoms. However, D was not associated with greater decline in cognitive functioning over the three-year follow-up period. Thus, although depressive symptoms may result in slight cognitive deficits in preclinical AD, at the time of the dementia diagnosis these effects may be absorbed by the neurodegenerative process.


[Breech Presentation: CNGOF Guidelines for Clinical Practice - Benefits and Risks for the Neonate and Child of Planned Vaginal Delivery versus Elective Cesarean Section].
To provide guidelines regarding the benefits and risks for the neonate and the child of planning vaginal delivery versus planning elective cesarean section in case of term breech presentation. MedLine and Cochrane Library databases search and review of the main foreign guidelines. In case of term breech presentation, planned vaginal delivery might be associated with an increased composite risk of perinatal mortality or occurrence of a combined outcome of serious neonatal morbidity in comparison to elective cesarean section (LE2). In case of planned vaginal delivery of term breech presentation, the risk of perinatal mortality is around 1‰ (LE3). It is potentially less but still exists in case of elective cesarean section (LE2). Risks of neonatal trauma - especially fracture of clavicle and breech hematoma -, Apgar score lower than 7 at 5minutes, and need for neonatal intubation and ventilation, are increased in case of planned vaginal delivery (LE2) and are around 1% (LE3). However, no difference has been demonstrated between planned vaginal and planned cesarean delivery regarding neurodevelopmental outcomes at 2 years (LE2), cognitive and psychomotor outcomes between 5 and 8 years (LE3), and adult intellectual performances (LE4). In case of term breech presentation, risks of severe complications for neonate and child are low in case of planned vaginal delivery or elective cesarean section. Short-term benefit/risk balance for the neonate might favor elective cesarean section but long-term morbidity seems to be similar whatever the delivery route (Professional consensus).


Anti pruritic effects of topical crotamiton, capsaicin, and a corticosteroid on pruritogen-induced scratching behavior.
Itch accompanies various skin diseases. As a number of mediators other than histamine can be involved in the itch sensation, H1 receptor antagonists are not necessarily effective in treating itch. External application of antipruritic drugs is occasionally used as an alternative therapy for pruritic skin conditions, such as pruritus on primary non-diseased, non-inflamed skin. Even so, the actual effects of these drugs on the itch sensation have yet to be studied in detail. To verify the antipruritic effects of crotamiton, capsaicin, and a corticosteroid on the itch sensation, we examined the inhibitory effects of these drugs on various pruritogen-induced scratching behaviors in mice. Topical application of 10% crotamiton moderately inhibited histamine-, serotonin-, and PAR-2 agonist-induced scratching behaviors. Topical capsaicin (0.025%) also exerted a moderate suppressive effect on histamine-, substance P-, and PAR-2 agonist-induced itch responses. Notably, topical corticosteroid (0.05% clobetasol propionate) remarkably inhibited the scratching behaviors induced by all of the pruritogenic agents tested. Therapeutic effects of capsaicin on substance P-induced pruritus did not seem to be mediated by desensitization of the TRPV1 (+) C fibers and/or by altered responsiveness of the mast cells. In addition, the antipruritic effects of crotamiton and corticosteroid appear to be, at least partly, associated with a TRPV1-independent pathway. This study examined the itch responses to pruritogens and demonstrated the mode of action of the externally applied antipruritic drugs.


Owl monkey CCR5 reveals synergism between CD4 and CCR5 in HIV-1 entry.
Studying HIV-1 replication in the presence of functionally related proteins from different species has helped define host determinants of HIV-1 infection. Humans and owl monkeys, but not macaques, encode a CD4 receptor that permits entry of transmissible HIV-1 variants due to a single residue difference. However, little is known about whether divergent CCR5 receptor proteins act as determinants of host-range. Here we show that both owl monkey (Aotus vociferans) CD4 and CCR5 receptors are functional for the entry of transmitted HIV-1 when paired with human versions of the other receptor. By contrast, the owl monkey CD4/CCR5 pair is generally a suboptimal receptor combination, although there is virus-specific variation in infection with owl monkey receptors. Introduction of the human residues 15Y and 16T within a sulfation motif into owl monkey CCR5 resulted in a gain of function. These findings suggest there is cross-talk between CD4 and CCR5 involving the sulfation motif.


Mathematical modeling of the fibrosis process in the implantation of inferior vena cava filters.
An inferior vena cava filter is a medical device that is implanted in the inferior vena cava and is in charge of capturing blood clots before they reach the lungs, preventing from pulmonary embolism. There are some clinical problems regarding the use of inferior vena cava filters. One of them is the difficulty when retrieving the device due to the remodeling of the vena cava. Huge effort has been made in creating computational models that reproduce tissue remodeling, but no attention has been paid to the fibrosis phenomenon occurring in the inferior vena cava. In this work, a continuum computational model that reproduces the fibrosis in the presence of an antithrombotic filter is presented. Diffusion-reaction equations are used for modeling the mass balance between species in the venous wall. The main species considered to play a key role in the process of fibrosis are smooth muscle cells, endothelial cells, matrix metalloproteinases, vascular growth factors and the extracellular matrix. The developed model has been implemented on an idealized axisymmetric geometric vena cava model. Moreover, a sensitivity analysis has been performed to study the parameters influence on the evolution of the model. Results show that the computational model is able to predict the behavior of the species considered and it captures the key characteristics of lesion growth and the healing process within a vein subjected to non-physiological mechanical forces. Our results suggests that the vessel wall response is mainly caused by the endothelium denudation area and the collagen turnover among other factors.


[The expression of Calbindin and Parvalbumin in auditory pathway of kit gene mutated C57BL/6J mouse].
To observe the expressions of Calbindin(CB) and Parvalbumin (PV), the two calcium-binding protein, in auditory pathway in mice of wild type C57BL/6J and kit⁺/kitW⁻ ²Bao, a kit gene mutant. Six mutated kit gene kit⁺/kitW⁻ ²Bao mice and 6 wild type C57BL/6J (B6) mice were anaesthetized i. p. with chloral hydrate. After the mice were fixed by heart perfusion, the brains were removed and coronal sections were cut with a freezing microtome. We found that wild type mice had significant expressions of PV on ventral cochlear nucleus, anterior part (AVCN), ventral cochlear nucleus, posterior part (PVCN), inferior colliculus (IC) and auditory cortex (AC). CB was expressed in wild type mice on PVCN and nucleus of the trapezoid body (Tz). The mutant of kit gene induced the less expression of PV on PVCN, IC and AC (P < 0.01), but increased the expression of Tz (P < 0.01). CB could not be observed on PVCN in mutant mice, and the expression of AC was increased( P < 0.01). CB and PV has differential expression level in auditory pathway. Since mutated kit gene can affect expression of PV on PVCN, IC, Tz and AC, as well as CB on PVCN and AC, it suggests that the mutation of kit gene can affect the advanced function of central nervous system in auditory pathway.


Intrathecally administered ropivacaine is less neurotoxic than procaine, bupivacaine, and levobupivacaine in a rat spinal model.
The aim of this study was to compare the neurotoxicity of intrathecal procaine, bupivacaine, levobupivacaine, and ropivacaine in an animal model. The study comprised two experiments. In the concentration experiment, rats (n = 78) were administered 0.12 μL·g(-1) body weight (BW) of 2% or 20% procaine, 0.5% or 5% bupivacaine, 0.5% or 5% levobupivacaine, or 0.5% or 5% ropivacaine. Based on the findings, the doses were increased by volume in the subsequent volume experiment using 0.12, 0.24, or 0.48 μL·g(-1) BW of 6% procaine, 6% levobupivacaine, or 6% ropivacaine (n = 79). Walking behaviour and sensory threshold were analyzed, and a histological examination of the spinal cord, posterior and anterior roots, and cauda equina was performed. The concentration experiment showed abnormalities only in the 5% bupivacaine group, and these abnormal findings were in the posterior root (PR) and posterior column (PC). The volume experiment revealed that procaine 0.24 μL·g(-1) was neurotoxic, mainly affecting the PR. At 0.48 μL·g(-1), severe injury was observed in the PR and PC in all six procaine rats and four of six levobupivacaine rats, while milder injury was limited to the PR in one of six ropivacaine rats, which differed significantly from the former two groups (P = 0.006 and P = 0.014, respectively). Electron microscopy showed axonal degeneration. All four local anesthetics seemed to cause identical neurotoxic lesions commencing in the PR and extending to the PC by axonal degeneration. Bupivacaine appeared to be the most neurotoxic of the four drugs, and the neurotoxicity at higher doses increased by volume with procaine > levobupivacaine > ropivacaine.


Changes in high-density lipoprotein subfraction distribution and increased cholesteryl ester transfer after probucol.
The effects of probucol (500 mg twice daily) on high-density lipoprotein (HDL) subfractions and cholesteryl ester transfer from HDL to lower density lipoproteins were tested in a series of patients with Type II hypercholesterolemia. In this placebo-controlled crossover trial, patients received probucol or placebo for 8 weeks, then switched to the other agent for another 8 weeks. Probucol significantly lowered total, low-density lipoprotein and HDL cholesterol levels. HDL subfractions, separated by rate zonal ultracentrifugation, showed a dramatic reduction in HDL2, whereas changes in HDL3 were not significant. Both subfractions eluted at a characteristically lower volume, indicating a reduced flotation rate. These findings were confirmed by gradient gel electrophoretic separation, which showed a typical reduction or disappearance of HDL2b particles and the prevalence of particles in the HDL3a-HDL3b electrophoretic range in almost all patients. After treatment, cholesteryl ester transfer from HDL to lower density lipoproteins was significantly increased in all patients. These data suggest that probucol may accelerate HDL particle conversion, leading to improvement in reverse cholesterol transport from the periphery to the liver, through HDL and very low density lipoprotein.


Simultaneous bilateral single-port radical nephrectomies.
The management of bilateral enhancing renal masses can be technically challenging. Simultaneous bilateral laparoscopic nephrectomies in postrenal transplant patients have been previously described, but these typically require multiple port placements in addition to a hand port. Herein, we describe simultaneous bilateral single-port laparoscopic radical nephrectomies in a postrenal transplant patient.


Establishing a nursing center: learning from the literature and the experiences of others.
In the midst of health care reform, academic nursing centers are well-positioned as cost-effective health care providers. As practice sites that are integral components of nursing academic units, these centers provide educational experiences for students, practice sites for faculty, nursing services to the community, and settings for nursing research. The success of these centers is determined by their ability to manage seven major issues of implementation: funding, integrating the center into the community, services, marketing, legal and regulatory issues, faculty issues, and research issues. While these issues require considerable attention, it is critical that centers capitalize on the opportunities provided by the current health policy climate.


Differentiation of muscle and the determination of ultimate tissue size.
The factors that determine ultimate muscle size have been studied using a "model" that involves two strains of mice, which had been especially bred for "largeness" (QL) and for "smallness" (QS). The difference in muscle size was not found to be due to a difference in fibre size, but due to a difference in fibre number. The muscles from the "QL" mice contained about 30% more fibres. The reason for this increased fibre number was investigated. During early development, the fusion of mononucleated presumptive myoblasts to form multinucleated myotubes took place at the same time in both "QL" and "OS" mice, as indicated by the appearance and increase in activity of ATP: creatine phosphotransferase. At this stage fibre (and cell) number and size could be determined by measuring nuclear number and protein/DNA ratio respectively. No difference in fibre (and cell) size could be found in mice at 5 days before birth, newly born, or at 20 days of age. At these ages it was found that the muscles from the "QL" mice contained a greater number of nuclei (muscle cells). The amount of RNA/nucleus was used as an index of protein synthetic rate, and no difference could be found between the large mice and the small mice. It was concluded that, in the case of the "QL" mice, the increased fibre number was not brought about by: (i) a delay in time of fusion of presumptive myoblasts; (ii) a smaller number of myoblasts fusing to form myotubes; or (iii) extensive fibre formation after fusion. Differences in fibre number, and hence muscle size, must therefore, presumably be caused by initial differences in the rate of proliferation of myoblasts before fusion.


Transferrin recycling in reticulocytes: pH and iron are important determinants of ligand binding and processing.
Iron uptake by rat reticulocytes is blocked by 20 mM NH4Cl, while 125I-diferric transferrin (Tf) uptake is relatively unaffected. At pH 5.0 both apo- and diferric Tf bind with high affinity; at pH 7.4 diferric Tf binds avidly, but apoTf binds very poorly. The dissociation rate (4 degrees C) of diferric Tf is extraordinarily slow at pH 5.0 (extrapolated t 1/2 = 32 hrs) and faster at pH 7.4 (t 1/2 = 101 min). At pH 5.0 apoTf also dissociates slowly (t 1/2 = 205 min), but at pH 7.4 apoTf exhibits a much faster dissociation rate (t 1/2 = 62 min). 20 mM NH4Cl slows the release of Tf from cells at 37 degrees C, but the rate of externalization of ligand is unaffected. Ligand dissociation at 37 degrees involves both externalization of receptor-ligand complexes and receptor-ligand separation; the NH4Cl effect may result from an increased fraction of externalized Tf in the diferric form which may dissociate more slowly. Receptor-mediated movement of Tf through acid intracellular compartments provides a mechanism to remove iron from Tf and for apoTf to remain receptor-bound for externalization to the cell surface and subsequent dissociation.


The association between greenery type and gut microbiome in schizophrenia: did all greenspaces play the equivalent role?
In recent years, attention has been focused on the benefit of greenspace on mental health, and it is suggested this link may vary with the type of greenspace. More and more studies have emphasized the influence of the gut microbiome on schizophrenia (SCZ). However, the effects of greenspaces on the gut microbiota in SCZ and the effect of different types of greenspaces on the gut microbiota remain unclear. We aim to examine if there were variations in the effects of various greenspace types on the gut microbiome in SCZ. Besides, we sink to explore important taxonomic compositions associated with different greenspace types. We recruited 243 objects with schizophrenia from Anhui Mental Health Center and collected fecal samples for 16Sr RNA gene sequencing. Three types of greenery coverage were calculated with different circular buffers (800, 1500, and 3000 m) corresponding to individual addresses. The association between greenspace and microbiome composition was analyzed with permutational analysis of variance (PERMANOVA). We conducted the linear regression to capture specific gut microbiome taxa associated with greenery coverage. Tree coverage was consistently associated with microbial composition in both 1500 m (R2 = 0.007, P = 0.030) and 3000 m (R2 = 0.007, P = 0.039). In contrast, there was no association with grass cover in any of the buffer zones. In the regression analysis, higher tree coverage was significantly correlated with the relative abundance of several taxa. Among them, tree coverage was positively associated with increased Bifidobacterium longum (β = 1.069, P = 0.004), which was the dominant composition in the gut microbiota. The relationship between greenspace and gut microbiome in SCZ differed by the type of greenspace. Besides, "tree coverage" may present a dominant effect on the important taxonomic composition. Our findings might provide instructive evidence for the design of urban greenspace to optimize health and well-being in SCZ as well as the whole people.


Acute muscle damage in latissimus dorsi grafts mobilized for cardiac assist: is vasospasm an important factor?
Muscle damage in latissimus dorsi grafts is known to occur following surgical mobilization for cardiomyoplasty. It is believed that ischemia may be a contributory factor. We tested the hypothesis that surgical manipulation of the muscle graft resulted in vasospasm of the intramuscular arteries that compromised muscle viability by examining the effects of vasodilators in the early ischemic period. Rat latissimus dorsi muscles were mobilized from all truncal attachments with preservation of the thoracodorsal neurovascular pedicle. Undisturbed contralateral muscles served as controls. After 24 hours, regional analysis of muscle viability was performed by enzyme macrohistochemistry and histologic assessment. The experimental interventions in four randomized groups (n = 5 each) included: group A, control; group B, topical papaverine (1%); group C, intravenous hydralazine (0.5 mg/kg); and group D, intravenous verapamil (75 microg/kg). All mobilized muscles showed loss of viability, as compared to controls, with damage most apparent in the distal part (mobilized vs control: viable area = 56.76% [51.26-62.26] vs 98.54% [97.87-99.21]; p < 0.001). All three vasodilators failed to prevent muscle necrosis whereas papaverine appeared to aggravate the damage (papaverine vs control: viable area = 53.60% [30.73-76.47] vs 76.60% [75.02-78.18] in the middle region; p < 0.05 and 44.27% [29.53-59.01] vs 56.76% [51.26-62.26] in the distal region; p < 0.05). The rodent model appears to be useful for studying latissimus dorsi muscle injury. The use of vasodilators at the time of surgical mobilization of the latissimus dorsi muscle does not appear to influence the degree of early muscle damage. Topical papaverine may be detrimental to the muscle in this regard.


Interaction of allogeneic adipose tissue-derived stromal cells and unstimulated immune cells in vitro: the impact of cell-to-cell contact and hypoxia in the local milieu.
Multipotent mesenchymal stem cells (MSCs) are an attractive tool for cell therapy and regenerative medicine. Being applied in vivo, allogeneic MSCs are faced with both activated and unstimulated immune cells. The effects of MSCs on activated immune cells are well described and are mainly suppressive. Less is known about the interaction of MSCs with unstimulated immune cells. We evaluated the contribution of tissue-related O2 level ("physiological" hypoxia-5% O2) and cell-to-cell contact to the interaction between allogeneic adipose tissue-derived MSCs (ASCs) and unstimulated peripheral blood mononuclear cells (PBMCs). Under both O2 levels, ASCs affected the immune response by elevating the proportion of CD69+ T cells and modifying the functional activity of unstimulated PBMCs, providing a significant reduction of ROS level and activation of lysosome compartment. "Physiological" hypoxia partially attenuated the ASC modulation of PBMC function, reducing CD69+ cell activation and more significantly supressing ROS. In direct co-culture, the ASC effects were more pronounced. PBMC viability was preferentially maintained, and the lymphocyte subset ratio was altered in favour of B cells. Our findings demonstrate that allogeneic ASCs do not enhance the activation of unstimulated immune cells and can provide supportive functions. The "hypoxic" phenotype of ASCs may be more "desirable" for the interaction with allogeneic immune cells that may be required in cell therapy protocols.


Long-term cardiovascular effects of high "osteoprotective" dose levels of 17 beta-estradiol in spontaneously hypertensive rats.
The effects of estrogen replacement therapy in menopausal women are more obvious on bones than on the cardiovascular system. The optimal estrogen dosage may differ in these different parts of the body. In hypertensive rats, low doses have been shown to reduce arterial collagen and stiffness, whereas higher dosages are required for osteoprotection. From 4 to 20 weeks of age, female spontaneously hypertensive rats (SHRs) were divided into four groups: without ovariectomy, under placebo or 17 beta-estradiol (10 micrograms/kg/day), and with ovariectomy under either placebo or 17 beta-estradiol (same dosage). Serial tail systolic blood pressure measurements were performed, and histomorphometry of the thoracic aorta was determined at the end of the study. Under estrogen, blood pressure was unchanged, whereas the aortic wall-to-lumen ratio was increased, particularly in the presence of ovariectomy. The elastin to collagen ratio was significantly decreased, due both to a decrease in elastin and an increase in collagen density, with no change in media thickness. The latter findings were not observed when ovariectomy was performed. Independent of changes in wall stress, high-dose estrogen increases the aortic extracellular matrix in female SHRs. This increase may be reversed in the presence of ovariectomy, suggesting that estrogen was not the only gonadal factor responsible for altered vascular structure and function.


Evaluating meaningful impact of Patient and Public Involvement: A Q methodology study among researchers and young people with a chronic condition.
Although Patient and Public Involvement (PPI) of young people with a chronic condition (YPCC) is receiving increasing attention, evidence of impact is lacking. This is partly due to inadequate understanding of what meaningful impact entails. This study aimed to gain an in-depth understanding of researchers' and YPCC's perspectives on meaningful impact. We conducted a Q methodology study in a group of 26 researchers and a group of 20 YPCC with experience in PPI. Participants ranked statements about impact (e.g., 'YPCC acquire new knowledge and skills') based on their agreement with them. During interviews, they reflected on their rankings (Q sorts). Factor analysis was conducted to identify similar patterns in the individual Q sorts. The interviews were used to determine and interpret the final factor solution. The resulting factors represented distinct perspectives on meaningful impact. Four distinct perspectives on meaningful impact of PPI were identified. Two were predominantly based on the Q sorts of researchers, for example improving research quality and facilitating dialogue and understanding, and two on the Q sorts of YPCC, for example achieving equality and inclusivity and doing justice to YPCC's rights. The factors were defined by 37 Q sorts (80%); 9 Q sorts did not load significantly on any of the factors. The results indicate that researchers and YPCC can have different views about the meaningful impact of PPI. The perspectives identified here can serve as an aid when discussing these different views and formulating operational indicators of impact. An adolescent with a chronic condition was involved in the early phases of this study. She helped in formulating the statements and recruiting YPCC.


Thyroid inclusion in the lung. Metastasis of an occult papillary carcinoma or ectopia?
The incidental autopsy finding of a thyroid inclusion in the lung of a 26-year-old man, accompanied by an occult papillary carcinoma (OPC) in the thyroid gland, raises the question about the possibility of true thyroid ectopia in the lung vs. metastasis of an OPC. Based on the embryonic development of the thyroid gland and the known thyroid ectopias, as well as on statistical figures on OPCs and their metastases, both possibilities are discussed. The histological pattern of the thyroid inclusion and the lack of regional nodal metastases argue in favour of ectopia, even though a definitive conclusion cannot be drawn.


Intravesical tape erosion following the tension-free vaginal tape procedure for stress urinary incontinence.
We report a case of intravesical tape erosion which occurred 6 months after the tension-free vaginal tape (TVT) procedure, which was successfully treated by partial tape removal. A 75-year-old woman, who had complained of recurrent cystitis after TVT procedure, was referred to Kobe City General Hospital in August 2003. The intravesical tape erosion was revealed by cystoscopy and computed tomography, and the tape was removed with a retropubic approach. The recurrent cystitis has been cured and the stress urinary incontinence has not recurred. The intravesical tape erosion was rare, with only seven reported cases including the present case.


Meiofauna communities, nematode diversity and C degradation rates in seagrass (Posidonia oceanica L.) and unvegetated sediments invaded by the algae Caulerpa cylindracea (Sonder).
We investigated meiofauna and sedimentary C cycling in seagrass (Posidonia oceanica) and unvegetated sediments invaded and not invaded by the non-indigenous tropical algae Caulerpa cylindracea. In both habitats, invaded sediments were characterized by higher organic matter contents. No effect was observed for prokaryotes and C degradation rates. In seagrass sediments, C turnover in invaded beds was about half that in not invaded ones. Meiofaunal communities varied significantly among invaded and not invaded grounds only in bare sediments. In both habitats, nematode species richness and assemblage composition were not affected by the algae. The effect of C. cylindracea on the turnover and nestedness components of the Jaccard dissimilarity varied between the two habitats. We show that the presence of C. cylindracea gives rise to variable consequences on meiofauna biodiversity and C cycling in different habitats. We conclude that further studies across different habitats and ecological components are needed to ultimately understand and predict the consequences of C. cylindracea invasion in shallow Mediterranean ecosystems.


Synthetic bone grafting with preserved cartilage flap via a medial malleolus osteotomy approach to treat osteochondral lesion of the talus: technical note and preliminary clinical results.
Although various surgical procedures are available for osteochondral lesion of the talus (OLT), there is still no consensus on its best treatment. The purposes of this study were to describe a new surgical technique to treat OLT and to analyze its preliminary clinical results. Eight patients were enrolled in this retrospective study between March 2019 and May 2022 in the Second Affiliated Hospital of Chongqing Medical University. All patients were treated by synthetic bone grafting with preserved cartilage flap via a medial malleolus osteotomy approach. The patients' characteristics, operative time, and estimated blood loss were evaluated. Intraoperative photos, preoperative and postoperative X-ray and MRI imaging were recorded. The American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and visual analog scale (VAS) score were also recorded before surgery and at each follow-up. At six months after the operation, all patients showed bone ingrowth and remodeling according to X-ray and MRI. No obvious defects or ladder was found on the cartilage surface of all patients according to MRI. The AOFAS score improved from 61.63 ± 8.85 (range, 49-74) to 91.13 ± 4.49 (range, 83-97) (p < 0.001) and VAS score improved from 5.50 ± 1.60 (range, 4-8) before surgery to 1.88 ± 0.83 (range, 1-3) (p < 0.001) at latest follow-up. In all eight patients, no wound infection, skin necrosis, or delayed healing of osteotomy was found. We proposed a simple and effective technique that restored the shape of the cartilage surface by preserving the cartilage flap and restoring the natural congruency of the subchondral bone by synthetic bone grafting. We found satisfying clinical outcomes in short-term follow-up. Our new technique might be a new surgical option for the treatment of OLT and its effectiveness should be further evaluated.