Structural validation and assessment of AlphaFold2 predictions for centrosomal and centriolar proteins and their complexes.
Obtaining the high-resolution structures of proteins and their complexes is a crucial aspect of understanding the mechanisms of life. Experimental structure determination methods are time-consuming, expensive and cannot keep pace with the growing number of protein sequences available through genomic DNA sequencing. Thus, the ability to accurately predict the structure of proteins from their sequence is a holy grail of structural and computational biology that would remove a bottleneck in our efforts to understand as well as rationally engineer living systems. Recent advances in protein structure prediction, in particular the breakthrough with the AI-based tool AlphaFold2 (AF2), hold promise for achieving this goal, but the practical utility of AF2 remains to be explored. Focusing on proteins with essential roles in centrosome and centriole biogenesis, we demonstrate the quality and usability of the AF2 prediction models and we show that they can provide important insights into the modular organization of two key players in this process, CEP192 and CEP44. Furthermore, we used the AF2 algorithm to elucidate and then experimentally validate previously unknown prime features in the structure of TTBK2 bound to CEP164, as well as the Chibby1-FAM92A complex for which no structural information was available to date. These findings have important implications in understanding the regulation and function of these complexes. Finally, we also discuss some practical limitations of AF2 and anticipate the implications for future research approaches in the centriole/centrosome field.


Recovering metal(loids) and rare earth elements from closed landfill sites without excavation: Leachate recirculation opportunities and challenges.
Metal (loids) and Rare Earth Elements (REE) ('metals') are used in a wide range of products, and therefore, the improvement of expectations for everyday comforts with demand continues to grow. Metal-bearing wastes are a secondary source of raw material that can meet this demand by providing a previously unconsidered low impact supply source. Total annual leachate production is 1,056,716 m3. Therefore, landfill leachate emerges as a significant potential resource as it contains high concentrations of metals. However, realising a profitable return on investment for leachate processing is a challenge due to relatively low recovery rates of approximately 0.02% of total heavy metals in a landfill being leached out in 30 years. Variation within the multi-element value and the effect of other chemicals in these complex mixtures. There is a need to better understand the mechanisms and potential applicability of extraction methods for optimising metals recovery from leachate. This paper addresses this need by providing a systematic review of the critical factors and environmental conditions that influence the behaviour of metals within the landfilled waste. The paper provides a synthesis of how the factors and conditions may affect leachate recirculation efficiency for recovery in the context of a range of opportunities and challenges facing circular economy practitioners. To approach feasibility metal recovery economically from landfill leachate without energy-intensive and environmentally destructive, future research actions need to be initiated in lab-based and later on semi-pilot to pilot studies, which the review can help achieve the challenges.


Economic evaluation of nebivolol in the treatment of hypertension.
To examine the economic consequences of effective antihypertensive treatment using the novel vasodilating beta1-adrenoceptor antagonist nebivolol (Nebilet) from the perspective of the healthcare provider. The evaluation was based on a postmarketing surveillance study in Germany involving 8682 moderately hypertensive patients. Using the Framingham Risk Model, the antihypertensive effectiveness of nebivolol after 6 weeks of treatment was extrapolated to estimate the reductions in 10-year risks of cardiovascular events. Data sources included direct costs for medical and invasive cardiovascular interventions in Germany, costs of therapy in the US and the UK, and estimates on the prevalence of cardiovascular events issued by the American Heart Association. Six-week antihypertensive treatment resulted in a DBP reduction of 13.7 mm Hg. The rate of responders, defined as those patients achieving DBP <90 mm Hg, was 70%. SBP was reduced by 26.1 mm Hg. According to the Framingham Risk Model, 313 deaths would be avoided. Coronary heart disease (CHD) could be reduced by 94 cases (from 1339 to 1245 events) and 150 strokes would be avoided (from 518 to 368 events) in a 10-year period. This reduction of 244 cardiovascular events among the 8682 patients investigated corresponded to cost savings of between Euro 250,000 and Euro 2.5 million, depending on the healthcare environment and the intervention applied. Treatment of moderately hypertensive patients with nebivolol can be considered cost effective. Nebivolol has the potential to decrease the overall long-term costs of medical care for patients with hypertension.


Outcomes analysis for 280 patients with cholangiocarcinoma treated with liver transplantation over an 18-year period.
Cholangiocarcinoma is an aggressive malignancy with 5-year survival rates<15%. Selected patients present with localized but unresectable disease and are candidates for orthotopic liver transplantation (OLT). The purpose of this study was to evaluate a multi-institutional experience with liver transplantation for this malignancy. Two hundred eighty patients with cholangiocarcinoma treated with OLT from 1987 to 2005 were identified in The United Network for Organ Sharing database. Patient and allograft survivals were calculated and the potential prognostic value of multiple clinicopathologic variables was assessed. At a median follow-up interval of 452 days (range: 0-6,166 days), 1- and 5-year patient survivals were 74 and 38%, respectively, with 49 actual 5-year survivors and 21 actual 10-year survivors. Posttransplant 1- and 5-year allograft survivals were 69 and 36%, respectively. Study variables associated with improved survivals included diagnosis of cholangiocarcinoma pre-OLT [5-year overall survival (OS): 68 vs. 20% for patients with incidental diagnoses at the time of OLT, p<0.001] and OLT after 1993 (5-year OS: 45 vs. 30% pre-1994, p<0.01). In contrast, the diagnosis of concomitant primary sclerosing cholangitis did not impact survivals (5-year OS: 41 vs. 50% without primary sclerosing cholangitis, p=0.402). Selected cholangiocarcinoma patients treated with OLT experience a survival benefit. Diagnosis of cancer prior to OLT allows for better staging and pre-OLT therapy that may translate into improved outcomes. These data support the continued development of multimodality cholangiocarcinoma treatment protocols that include OLT.


Timing of cardiac transplantation in idiopathic dilated cardiomyopathy.
Seventy-nine patients with idiopathic dilated cardiomyopathy were assessed and followed up to evaluate 9 variables that might predict duration of survival after assessment for cardiac transplantation. Patients with ischemic heart disease, alcoholic and peripartum cardiomyopathy were excluded. There were 38 deaths (48%) during the 18-month (mean) follow-up. Patients underwent determination of left ventricular ejection fraction by radionuclide scan, echocardiography, cardiac catheterization and myocardial biopsy. Only left ventricular ejection fraction determined by radionuclide study correlated significantly with time to death in nonsurvivors (r = 0.38, p less than 0.05). Multivariant analysis and Cox multivariate regression analysis revealed that the single consistent determinant of prognosis was radionuclide-determined ejection fraction. It was an excellent predictor of survival to 3 months (p less than 0.0001) and a reasonable predictor of survival to 6 months (p less than 0.05). There was no variable that efficiently predicted survival for any period greater than 6 months. In 15 of 70 patients (21% of the entire group), clinical status and radionuclide ejection fraction improved after assessment but only one of these had an ejection fraction less than or equal to 0.10. No patient with a radionuclide ejection fraction greater than or equal to 0.20 died within 6 months of assessment. For those with ejection fraction between 0.11 and 0.19, survival after cardiac transplantation exceeded that of the natural history of their disease; this suggests that transplantation should be undertaken within 6 to 12 months of assessment. Left ventricular ejection fraction less than or equal to 0.10 predicts an extremely poor prognosis (6-month survival was 17%) and such patients should be transplanted with minimal delay.


The C-reactive protein to albumin ratio predicts postoperative complication in patients who undergo gastrectomy for gastric cancer.
The aim of this study was to evaluate the preoperative C-reactive protein (CRP) to albumin ratio (CAR) of patients with gastric cancer and to investigate the factors correlated with perioperative complications. From March 2016 to December 2019, 128 patients who underwent curative gastrectomy for gastric cancer were enrolled in a retrospective study. The preoperative cutoff value of the CAR for predicting postoperative complications was 0.265 on receiver operating characteristic (ROC) curve analysis. Clinical characteristics were compared between patients with complications (Clavien-Dindo grade ≥2, n = 20) and without complications (Clavien-Dindo grade <2, n = 108). On univariate and multivariate analyses, estimated blood loss (EBL) during the operation (HR 1.003, p = 0.039) and CAR (HR 2.832, p = 0.045) were independent predictors of postoperative complications. In conclusion, preoperative CAR appears to be a predictor of postoperative complications in the patients undergoing surgical treatment of gastric cancer.


An alternative mechanism of crossed vertical gaze palsy in unilateral mesodiencephalic infarction.
Crossed vertical gaze palsy refers to a rare combination of elevation paresis in one eye and depression palsy in the fellow eye. It was once reported in a patient with unilateral infarction involving the mesodiencephalic junction, and was ascribed to selective disruption of the fibers projecting from the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) to the oculomotor nuclear complex. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare cause of ophthalmoplegia and crossed vertical gaze palsy has not been described in this disorder. Our patient with a circumscribed acute infarction involving the left mesodiencephalic junction due to CADASIL showed both upward and downward gaze palsy in both eyes, but more marked depression paresis in the ipsilesional eye and more conspicuous elevation deficit in the contralesional eye, which was consistent with crossed vertical gaze palsy. We provide alternate explanation for this rare phenotype of vertical gaze palsy. Selective disruption of riMLF fibers may cause crossed vertical gaze palsy in unilateral mesodiencephalic lesion.


Why are we performing fewer cholecystectomies for mild acute biliary pancreatitis? Trends and predictors of cholecystectomy from the National Readmissions Database (2010-2014).
Current guidelines recommend cholecystectomy for patients with mild acute biliary pancreatitis (MABP) during the index admission because it is associated with better outcomes. In this study, we aimed to assess national trends in cholecystectomy during index admissions for MABP and to identify factors associated with cholecystectomy completion and 30-day readmission. Using diagnostic codes and the National Readmissions Database, we identified patients admitted with MABP between 2010 and 2014. Differences in cholecystectomy rates were computed on the basis of various characteristics. We conducted a multivariable analysis to identify factors associated with 30-day readmission and cholecystectomy during the same admission. We identified 255,695 unique index MABP cases (41.3% male) and the 30-day readmission rate was 12.6%. Overall, 43.8% underwent cholecystectomy and 25% underwent endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy. We observed a decreasing trend in both procedures during the study period (P < 0.001). In multivariate analysis, odds of 30-day readmission were reduced for patients undergoing ERCP with sphincterotomy (odds ratio, 0.78; 95% confidence interval, 0.74-0.84) or cholecystectomy (odds ratio, 0.37; 95% confidence interval, 0.35-0.39). For patients with MABP, cholecystectomy or ERCP with sphincterotomy during the index admission decreased the risk of 30-day readmission. Despite this benefit and national guidelines recommending cholecystectomy during the index MABP admission, the rate of cholecystectomies performed nationally decreased during the study period. Further research is needed to understand the implications and reasons underlying this deviation from guidelines.


Selective labeling of apomorphine receptors by 3H-LSD.
There are at least two types of dopamine receptors: the 3H-dopamine or 3H-apomorphine receptor (with high or nM affinity for dopamine), and the 3H-neuroleptic receptor (with low or microM affinity for dopamine). While 3H-LSD can label the 3H-neuroleptic receptor, this study was done in order to label the 3H-apomorphine/dopamine receptor site. In the presence of excess phentolamine, serotonin and spiperone (to preclude binding to alpha-adrenergic, serotonergic and neuroleptic receptors, respectively) similar concentrations of dopaminergic drugs inhibited the binding (to calf caudate) of 3H-LSD and 3H-apomorphine. This is compatible with the concept that the 3H-apomorphine/dopamine receptor and the 3H-neuroleptic/dopamine receptor are separate.


[Effect of sodium oxybutyrate, phenamin, transamine and L-dopa on the processes of work capacity recovery under conditions of minimal rest].
The action of sodium oxybutyrate, phenamine transamine and L-DOPA on the processes of re-establishing the mental and physical performance capacity after fatigue was studied in experiments with rats. The activating effect of sodium oxybutyrate on the resotration of performance capacity in these conditions is shown not to be inferior to an analogous action of phenamine. Complete re-establishment of performance capacity is recorded against the background of the action produced by a monoaminoxidase inhibitor-transamine, as well as combinations of sodium oxybutyrate and L-DOPA.


B12Hn and B12Fn: planar vs icosahedral structures.
Using density functional theory and quantum Monte Carlo calculations, we show that B12Hn and B12Fn (n = 0 to 4) quasi-planar structures are energetically more favorable than the corresponding icosahedral clusters. Moreover, we show that the fully planar B12F6 cluster is more stable than the three-dimensional counterpart. These results open up the possibility of designing larger boron-based nanostructures starting from quasi-planar or fully planar building blocks.


Rapid synthesis of oligodeoxyribonucleotides. II. Machine-aided solid-phase syntheses of two nonanucleotides and an octanucleotide.
Preparation of the two nonanucleotides, d(pG-G-A-G-G-A-G-A-A) and d(pT-T-C-T-G-T-T-G-A), and the octanucleotide, d(pT-G-G-C-C-C-A-T) is described by a rapid solid-phase method on a polyamide support. The syntheses were carried out using a modified solid-phase peptide synthesiser and required one day for each nucleotide addition. A microparticulate anion-exchanger, Partisil 10SAX, was used for the efficient fractionation of synthetic, base-protected oligonucleotides.


Room temperature and low-field resonant enhancement of spin Seebeck effect in partially compensated magnets.
Resonant enhancement of spin Seebeck effect (SSE) due to phonons was recently discovered in Y[Formula: see text]Fe[Formula: see text]O[Formula: see text] (YIG). This effect is explained by hybridization between the magnon and phonon dispersions. However, this effect was observed at low temperatures and high magnetic fields, limiting the scope for applications. Here we report observation of phonon-resonant enhancement of SSE at room temperature and low magnetic field. We observe in Lu[Formula: see text]BiFe[Formula: see text]GaO[Formula: see text] an enhancement 700% greater than that in a YIG film and at very low magnetic fields around 10[Formula: see text] T, almost one order of magnitude lower than that of YIG. The result can be explained by the change in the magnon dispersion induced by magnetic compensation due to the presence of non-magnetic ion substitutions. Our study provides a way to tune the magnon response in a crystal by chemical doping, with potential applications for spintronic devices.


How does agricultural production outsourcing services affect chemical fertilizer use under topographic constraints: a farm-level analysis of China.
Agricultural production outsourcing services (APOS) are an important means to promote green and low-carbon development of agriculture in China. Topography is the key factor limiting the development of APOS. There is little research on the influence relationship between APOS and farmers' chemical fertilizer use from the perspective of topography. Based on the theory of economies of scale, this study empirically evaluated the effect of APOS on chemical fertilizer use and their differences from the perspective of nutrient elements under different topographic conditions by using micro survey data for farmers in China and econometric methods. The results show that APOS can reduce farmers' chemical fertilizer use, and this effect is more obvious for farmers with large farmland sizes and high education levels. Farmland topography directly affects the fertilizer reduction effect of APOS in China. Compared with plain areas, hilly and mountainous areas weaken this effect. To enhance the fertilizer reduction effect of APOS, China should fully consider farmland topography when promoting APOS development. In plain areas, farmland scale management should be further encourage to better utilize APOS as a means of reducing chemical fertilizer use. In hilly and mountainous areas, high-standard farmland construction and small agricultural machinery use can alleviate the constraints of topographical on the scale expansion of APOS. It is necessary to fully consider the differences in farmers' resource endowments and their awareness of purchasing agricultural services in promoting APOS development, especially in regard to the farmers with small farmland sizes and low education levels.


Exploratory behavior and the dual activity of some psychoactive drugs. Part 5. Alcohol.
Alcohol is reported to impair acquisition and learning processes and it is considered a depressant of the brain activities impairing rapidity and consistency of some behaviors. The experiments reported here are concerned with the exploratory performances of the already described subpopulations of Albino mice under the effect of alcohols of different types.


Multimethod quantification of Ag+ release from nanosilver.
There is a significant interest in determining the effects of nanomaterials on the environment and human health. Part or all of the toxicity attributed to silver nanoparticles (nAg) may be due to the release of free silver (Ag(+)). Therefore, it is necessary to have techniques that will allow the precise determination of free Ag(+) within suspensions of nAg particles. Among the different methods used for the determination of free metals in natural waters, the ion-exchange technique (IET), has promise to both distinguish Ag(+) from nAg and to attain the low detection limits required for the analysis of natural samples. In this paper, IET. centrifugal ultrafiltration and single particle inductively coupled plasma mass spectrometry (SP ICP-MS) were used to determine very low concentrations of free or dissolved Ag in commercial suspensions of nAg. Dilution of the silver nanoparticles played an important role in the measured Ag(+) concentrations. The relative release of Ag(+) from nAg increased as samples were increasingly diluted, implying that it is critical to determine Ag(+) concentrations under the precise conditions used for determinations of toxicological or environmental fate.


Post-hoc analysis of a randomized controlled trial on the impact of pre-transplant use of probiotics on outcomes after liver transplantation.
Perioperative use of probiotics serves as efficient prophylaxis against postoperative infections after liver transplantation, yet data on long-term effects of pre-transplant probiotic intake is lacking. The aim of this study was to assess the effects of pre-transplant probiotic administration on long-term results of liver transplantation. This was secondary analysis of a randomized trial. Patients were randomized to receive either 4-strain probiotic or placebo before liver transplantation. Five year graft survival was set as the primary end-point. Secondary end-points comprised serum bilirubin and C-reactive protein (CRP) concentration, international normalized ratio (INR), serum transaminases and gamma-glutamyl transferase (GGT) activity. Study group comprised 44 patients, of whom 21 received probiotics and 23 received placebo with 5-year graft survival of 81.0% and 87.0%, respectively (p = 0.591). Patients in the probiotic arm exhibited lower INR (p = 0.001) and CRP (p = 0.030) over the first 6 post-transplant months. In the absence of hepatitis B or C virus infection, pre-transplant administration of probiotics also reduced aspartate transaminase activity (p = 0.032). In the intervention arm, patients receiving probiotics for under and over 30 days had 5-year graft survival rates of 100% and 66.7%, respectively (p = 0.061). Duration of probiotic intake > 30 days was additionally associated with increased INR (p = 0.031), GGT (p = 0.032) and a tendency towards increased bilirubin (p = 0.074) over first 6 post-transplant months. Pre-transplant administration of probiotics has mild positive influence on 6-month allograft function, yet should not exceed 30 days due to potential negative effects on long-term outcomes. (ClinicalTrials.gov Identifier: NCT01735591).


Melt-and-mold fabrication (MnM-Fab) of reconfigurable low-cost devices for use in resource-limited settings.
Interest in low-cost analytical devices (especially for diagnostics) has recently increased; however, concomitant translation to the field has been slow, in part due to personnel and supply-chain challenges in resource-limited settings. Overcoming some of these challenges require the development of a method that takes advantage of locally available resources and/or skills. We report a Melt-and-mold fabrication (MnM Fab) approach to low-cost and simple devices that has the potential to be adapted locally since it requires a single material that is recyclable and simple skills to access multiple devices. We demonstrated this potential by fabricating entry level bio-analytical devices using an affordable low-melting metal alloy, Field's metal, with molds produced from known materials such as plastic (acrylonitrile-butadiene-styrene (ABS)), glass, and paper. We fabricated optical gratings then 4×4 well plates using the same recycled piece of metal. We then reconfigured the well plates into rapid prototype microfluidic devices with which we demonstrated laminar flow, droplet generation, and bubble formation from T-shaped channels. We conclude that this MnM-Fab method is capable of addressing some challenges typically encountered with device translation, such as technical know-how or material supply, and that it can be applied to other devices, as needed in the field, using a single moldable material.


Quick and reliable galactomannan detection in crude minced lung specimens from haematological patients with suspected invasive fungal infection: results from a case series.
Invasive aspergillosis (IA) is the leading direct or contributory cause of death in patients with haematological malignancies. Early diagnosis remains difficult and often elusive due the heterogeneity of clinical presentations and the low sensitivity of both histological examination and cultures of specimens obtained from patients at risk. We report two cases of IA, both of which lacked both histological and cultural evidence of IA from pulmonary specimens. In both patients, detection of galactomannan (GM) by enzyme immunoassay (EIA) on pulmonary tissue homogenates led to the diagnosis of IA, which was confirmed by Aspergillus DNA (real time PCR). In conclusion, we provide preliminary evidence that lung homogenates may be prepared for GM EIA assays, which may contribute to quick diagnosis of IA on otherwise negative samples. We feel that our results open up the opportunity of a prospective and comparative evaluation of this diagnostic technique.


Comparison of the suppression of cell and virus growth in transformed human cells of leukocyte and fibroblast interferon.
The effects of human leukocyte interferon (Le-IF) and fibroblast interferon (F-IF) on the growth of the transformed human cell lines, RSa and RSb, were compared. Both were considerably more sensitive to F-IF than to Le-IF. Two cell lines, IFr and F-IFr, derived from the RSa cell line, were resistant to the anticellular effects of Le-IF, but less resistant to those of F-IF.


Anti-MUC1 nanobody can synergize the Tamoxifen and Herceptin effects on breast cancer cells by inducing ER, PR and HER2 overexpression.
One of the most pressing concerns associated with breast cancer-targeted therapies is resistance to Tamoxifen and Herceptin. Such drug resistance is usually characterized by reduced expression of certain cell surface receptors. Some biological regimens can induce perceptible overexpression of these receptors in favor of drug responsiveness. In this research, drug-responsive MCF-7 and SKBR-3, along with drug-resistant MCF-7R (Tamoxifen resistant) and JIMT-1 (Herceptin resistant) breast cancer cell lines in 2D and 3D cultures were exposed to anti-MUC1 nanobody and then assessed for their ER, PR, and HER2 gene and protein expression using qRT-PCR and immunofluorescent staining analyses. Cell viability and the synergistic relationships of combination treatments were determined with MTT assay followed by CompuSyn software. Apoptotic cells were evaluated with Annexin V/propidium Iodide (PI) and acridine orange/ethidium bromide (AO/EB) staining. Anti-MUC1 exposure elevated the expression levels of ER (42 folds), PR (18.5 folds), and HER2 (4.7 folds). As a result of co-treatment, the IC50 levels for Tamoxifen and Herceptin were reduced by up to 10 and 3 folds, respectively. MCF-7R cells responded positively to Tamoxifen, as evidenced by a 5-fold reduction in the IC50 and enhanced apoptosis. The ER, PR, and HER2 overexpression after MUC1 blocking could signal drug hypersensitization and facilitate drug resistance management.


Ullmann Reaction of Aryl Chlorides on Various Surfaces and the Application in Stepwise Growth of 2D Covalent Organic Frameworks.
On-surface Ullmann coupling reaction of aryl chlorides has been achieved on Cu(111), Ag(111), and Au(111), and the mechanism has been investigated on the single molecule level using scanning tunneling microscopy and density functional theory. The different reactivity of the aryl halides was utilized to design a stepwise on-surface synthesis, which affords a zigzag template and then converts to 2D porous networks.


Cutaneous metastases from solid neoplasms - Literature review.
Cutaneous metastases from solid tumors are uncommon events in clinical practice. Most of the time, the patient already has the diagnosis of a malignant neoplasm when the cutaneous metastasis is detected. However, in up to one-third of cases, cutaneous metastasis is identified before the primary tumor. Therefore, its identification may be essential for starting treatment, although it is usually indicative of poor prognosis. The diagnosis will depend on clinical, histopathological, and immunohistochemical analysis. Sometimes the identification of the primary site is difficult; however, a thorough analysis using imaging tests and constant surveillance is important.


Effects of intracoelomic alfaxalone-dexmedetomidine on righting reflex in common garter snakes (Thamnophis sirtalis): preliminary data.
To evaluate the effect of dexmedetomidine on alfaxalone immobilization in snakes. Nonblinded, crossover study. A total of eight mature common garter snakes (Thamnophis sirtalis). Snakes were administered each of three treatments intracoelomically: alfaxalone (30 mg kg-1; treatment A), alfaxalone (30 mg kg-1) combined with dexmedetomidine (0.05 mg kg-1; treatment AD0.05); and alfaxalone (30 mg kg-1) combined with dexmedetomidine (0.10 mg kg-1; treatment AD0.10). A minimum of 10 days elapsed between experimental trials. Times to loss of righting reflex (LRR) and return of righting reflex (RRR) were recorded. Heart rate (HR) was recorded every 5 minutes throughout the period of LRR and averaged for each snake. Times to LRR and RRR, and mean HR in snakes that achieved LRR were reported. LRR occurred in eight (100%), five (63%) and three (38%) snakes in treatments A, AD0.05 and AD0.10, respectively. For all treatments, time to LRR ranged 3-20 minutes. Median (range) times to RRR were 39 (30-46), 89 (62-128) and 77 (30-185) minutes for treatments A, AD0.05 and AD0.10, respectively. In animals where righting reflex was lost, mean HR was lower in all dexmedetomidine treatments compared with treatment A. In this pilot study, alfaxalone resulted in reliable immobilization, whereas dexmedetomidine and alfaxalone combinations resulted in highly variable durations of immobilization with low HR in immobilized animals. For snakes that achieved LRR, the addition of dexmedetomidine (0.05 mg kg-1) to alfaxalone appeared to extend the period of immobilization compared with alfaxalone alone.


Esophageal fistula sealing: choice of stent, practical management, and cost.
Three models of covered metal stents are available to seal esophageal fistulas. Stainless steel covered stents were inserted in 5 patients (group I); nitinol covered stents were inserted in 12 patients (group II) with malignant (n = 14) or benign (n = 3) esophageal fistulas. Stent positioning was satisfactory in all cases. Fistula sealing was complete in 1 of 5 (20%) and 12 of 12 (100%) patients of groups I and II, respectively (p < 0.005). Continued esophageal leakage was initially related to the passage of fluids alongside the stent covering (n = 3) and to early stent migration (n = 1). Complications related to stent placement were observed in 2 of 17 (12%) patients and were fatal. During follow-up (mean 153 +/- 143 days), esophageal fistulas relapsed after initial sealing in 5 of 13 (38%) patients. Further treatment (glue or fibrin sealant injection, additional stent insertion) was attempted in 7 cases of persistent or relapsing esophageal fistula, with sealing obtained in 5 of them. The costs per patient and per day free from symptoms due to the esophageal fistula were $106 and $57 in groups I and II, respectively. Nitinol covered stents more frequently provided complete esophageal fistula sealing, as compared with stainless steel covered stents. Further treatments tailored to the mechanisms of fistula persistence or relapse often provided sealing.


Impact of Postoperative Changes in Brain Anatomy on Target Volume Delineation for High-Grade Glioma.
High-grade glioma has a poor prognosis, and radiation therapy plays a crucial role in its management. Every step of treatment planning should thus be optimised to maximise survival chances and minimise radiation-induced toxicity. Here, we compare structures needed for target volume delineation between an immediate postoperative magnetic resonance imaging (MRI) and a radiation treatment planning MRI to establish the need for the latter. Twenty-eight patients were included, with a median interval between MRIs (range) of 19.5 (8-50) days. There was a mean change in resection cavity position (range) of 3.04 ± 3.90 (0-22.1) mm, with greater positional changes in skull-distant (>25 mm) resection cavity borders when compared to skull-near (≤25 mm) counterparts (p < 0.001). The mean differences in resection cavity and surrounding oedema and FLAIR hyperintensity volumes were -32.0 ± 29.6% and -38.0 ± 25.0%, respectively, whereas the mean difference in midline shift (range) was -2.64 ± 2.73 (0-11) mm. These data indicate marked short-term volumetric changes and support the role of an MRI to aid in target volume delineation as close to radiation treatment start as possible. Planning adapted to the actual anatomy at the time of radiation limits the risk of geographic miss and might thus improve outcomes in patients undergoing adjuvant radiation for high-grade glioma.


Fleshflies in the flesh: epidemiology, population genetics and control of outbreaks of traumatic myiasis in the Mediterranean Basin.
Although the damaging effects on healthy tissues of its developing larvae were first described in 1770, the fleshfly Wohlfahrtia magnifica remains a serious pest for the livestock industry. Wohlfahrtiosis, the severe myiasis caused by this fly, is a grave problem in terms of both the animal welfare and economic loss. This review highlights important aspects of the biology, pest status, epidemiology, population genetic structure, economics and control of W. magnifica and wohlfahrtiosis, with an emphasis on recent outbreaks in Greece and Morocco and fly population dynamics in the Mediterranean Basin. Potential areas for future studies on genetics, host tolerance, in vitro rearing, field behaviour and range expansion of the species are also discussed.


Above- and below-ground environmental influences on leaf conductance ofCeanothus thyrsiflorus growing in a chaparral environment: drought response and the role of abscisic acid.
Small shrubs ofCeanothus thyrsiflorus were grown in 19-1 pots irrigated under natural conditions in a chaparral region of Southern California and then subjected to soil drying. Characteristics of leaf gas exchange, leaf water potential, and concentrations of the stress hormone abscisic acid in the xylem sap, ABAxyl, were determined at various stages of drought. Diurnal changes in conductance were strongly correlated with leaf net photosynthesis rate, which provides an effective, integrative predictor of above-ground climate effects on conductance. In drought conditions, ABAxyl concentration increased. Increases in the concentration range of 50-500 nmol/l appeared to induce stomatal closure, restricting water loss and carbon dioxide uptake. When the momentary water potential is related to ABAxyl, ABA appeared to increase significantly only after a threshold of approximately -1.5 MPa was exceeded. At less negative water potentials, large variation in ABAxyl in the 50-1000 nmol/l range occurred for all water-potential values, because ABAxyl remains relatively constant over diurnal courses as water potentials decrease and then recover. When the water potential became more negative than -1.5 MPa, ABAxyl concentrations occurred between approximately 500 and 10 000 nmol/l and even greater in isolated cases. An approximately linear relationship is recognizable between ABAxyl and momentary water potential in this range because in plants under drought conditions, ABAxyl increases during the course of the day as water potential decreases. Increases in ABAxyl in the high concentration range were associated with relatively minor additional restrictions in gas exchange, but they might contribute to improved water use efficiency and explain diurnal changes in the potential for stomatal opening that have been observed in Mediterranean sclerophyllous species. When we examined long-term seasonal change in the response of irrigated plants, changes in average daily temperature greater than 10°C occurred (also associated with shifts in relative humidity and radiation input), which apparently led to small changes in predawn water potential in the -0.1 to -0.7 MPa range. Increases in ABAxyl occurred that were in turn negatively correlated with daily maximum leaf conductance. Thus, chaparral shrubs under non-drought conditions seem to sense even small changes in environmental conditions, in our opinion most probably due to initial drying of the uppermost soil and synthesis of ABA in the shallow roots. The results support the hypothesis that information of photosynthesis rate and predawn water potential may be used as primary variables to predict canopy conductance of Mediterranean sclerophyll shrub vegetation.


Quality of life aspects in the management of thyroid cancer.
While there is agreement that quality of life (QoL) is a central aim of medical treatment, the methods of its evaluation as well as its role in the patient's overall treatment experience are under continuous scrutiny. Different perspectives on patients' QoL have emerged; from the treating physician, from the psychologist, and naturally from the patient him/herself. This article provides insights into each of these views within the context of thyroid cancer where, as a consequence of increasing incidence and decreasing mortality rates, QoL aspects deserve close attention. Physicians often find themselves in situations where they perform a balancing act between what they know is best from a somatic point of view and learning about what is best for the individual patient. For psychologists in the field of oncology, a main area of interest is the incorporation of the patient's perspective into research by using patient-reported outcomes (PROs) which include QoL assessment. PROs can also be used in clinical practice as a way to start a conversation about symptoms and QoL aspects that perhaps patients might not volunteer, and this allows physicians to address QoL issues more directly. Patients usually appreciate being asked about all aspects of QoL, and need sound information about how their QoL might be affected by the disease and its treatment. By examining and understanding the different perspectives on QoL, and how QoL differs in patients with thyroid cancer compared with other cancers, it is hoped that the QoL can be enhanced in this particular patient group.


Assessment and risk modeling of airborne enteric viruses emitted from wastewater reused for irrigation.
Reclamation of wastewater (WW) for irrigation, after treatment represents a challenge that could alleviate pressure on water resources and address the increasing demand for agriculture. However, the risks to human health must be assessed, particularly those related to human enteric viruses that resist standard treatments in most wastewater treatment plants (WWTP). The risks associated with exposure to viral bioaerosols near WWTP and near agricultural plots irrigated with WW are poorly documented. The objectives of this study were to 1) better characterize human enteric viruses found in bioaerosols near a "standard WWTP" and over fields irrigated with treated WW and 2) propose a numeric model to assess the health risk to populations located close to the irrigated areas, with particular attention to norovirus, which is responsible for most viral gastroenteritis in France. Water and air samples were collected at various locations in the largest French WW-irrigated site near Clermont-Ferrand, at the WWTP entrance and after treatment, in the air above activated sludge basins, and above fields irrigated with WW. Various enteric viruses were found in the water samples collected both before and after treatment. Norovirus was the most abundant with >10e4 genome copies/l (GC/L) before treatment and ~10e3 GC/L after treatment. Low quantities (<10e3GC/m3) were detected in the air above active sludge pools and irrigated plots. Hepatitis E virus was detected in all sampled compartments. A quantitative microbial risk assessment (QMRA) approach, including a simplified atmospheric dispersion model, allowed assessment of norovirus infection risk. The Bayesian QMRA approach considered wind speed measurements over 21years, and the variability and uncertainty of all measurements throughout the chain up to the risk. The probability of infection within one year for the most exposed WWTP employees was >10e-4 for strong wind speed (≥3m/s) and a constant emission rate of 8e3 GC/m3/s. This probability decreases by 3 log when the distance to the emission source is doubled. This information can aid development of safe water reuse policies in terms of local setback distance and wind conditions for wastewater reuse.


Reduced serum 25-hydroxyvitamin D concentration and disordered mineral metabolism in patients with cystic fibrosis.
Vitamin D and mineral metabolism were studied in 21 adolescents and young adults with cystic fibrosis and the results were compared to those in 21 matched controls. All CF patients had been maintained on standard multivitamin supplements in combination with pancreatic enzyme replacement. Despite this supplementation, relative to control subjects the CF patients had a 36% reduction in serum 25-hydroxyvitamin D concentration, a slight but significant reduction in serum calcium concentration, evidence of calcium malabsorption with secondary hyperparathyroidism, and a 14% decrease in bone mass measured by the photon absorption technique. Currently accepted modes of pancreatic enzyme replacement and vitamin D supplementation are often inadequate to maintain normal mineral homeostasis in CF patients; additional measurements may be required to reduce the risk of clinically significant osteopenia concomitant with prolonged survival in CF.


Anti-aging Effects of Mangosteen Peel Extract and Its Phytochemical Compounds: Antioxidant Activity, Enzyme Inhibition and Molecular Docking Simulation.
Skin aging is a complex natural process characterised by gradual diminishment of structural integrity and physiological imbalance of the skin tissue. Since the oxidative stress is tightly corelated to the skin aging process, the usage of antioxidant may serve as favourable strategies for slowing down the skin aging process. Mangosteen is an important fruit commodity and its extract had been extensively studied and revealing various biological activities. Present study aimed to assess the antioxidant and antiaging activity of mangosteen peel extract (MPE) and its phytochemical compounds. MPE and its compounds were subjected to ferric reducing antioxidant power (FRAP), hydroperoxide (H2O2) scavenging, anti-collagenase, anti-elastase, anti-hyaluronidase and anti-tyrosinase assay. MPE has the highest FRAP 116.31 ± 0.60 μM Fe(II) μg-1 extract, IC50 of MPE on H2O2 scavenging activity was 54.61 μg mL-1. MPE also has the highest anti elastase activity at IC50 7.40 μg mL-1. Alpha-mangostin showed potent anti-collagenase activity (IC50 9.75 μg mL-1). While gamma-mangostin showed potent anti-hyaluronidase (IC50 23.85 μg mL-1) and anti-tyrosinase (IC50 50.35 μg mL-1). MPE and its compounds were evaluated in vitro for antioxidant and antiaging activities. Current findings may provide scientific evidence for possible usage of mangosteen extract and its compounds as antioxidant and antiaging agent.


Genetic variation and activity of the renin-angiotensin system and severe hypoglycemia in type 1 diabetes.
The deletion-allele of the angiotensin-converting enzyme (ACE) gene and elevated ACE activity are associated with increased risk of severe hypoglycemia in type 1 diabetes. We explored whether genetic and phenotypic variations in other components of the renin-angiotensin system are similarly associated. Episodes of severe hypoglycemia were recorded in 171 consecutive type 1 diabetic outpatients during a 1-year follow-up. Participants were characterized at baseline by gene polymorphisms in angiotensinogen, ACE, angiotensin-II receptor types 1 (AT1R) and 2 (AT2R), and by plasma angiotensinogen concentration and serum ACE activity. Three risk factors for severe hypoglycemia were identified: plasma angiotensinogen concentration in the upper quartile (relative rate [RR] vs. lower quartile 3.1, 95% confidence interval [CI,] 1.4-6.8), serum ACE activity in the upper quartile (RR vs. lower quartile 2.9, 95% CI, 1.3-6.2), and homo- or hemizygosity for the A-allele of the X chromosome-located AT2R 1675G/A polymorphism (RR vs. noncarriers 2.5, 95% CI, 1.4-5.0). The three risk factors contributed independently to prediction of severe hypoglycemia. A backward multiple regression analysis identified a high number of renin-angiotensin system-related risk factors and reduced ability to perceive hypoglycemic warning symptoms (impaired hypoglycemia awareness) as predictors of severe hypoglycemia. High renin-angiotensin system activity and the A-allele of the AT2R 1675G/A polymorphism associate with high risk of severe hypoglycemia in type 1 diabetes. A potential preventive effect of renin-angiotensin system blocking drugs in patients with recurrent severe hypoglycemia merits further investigation.


Cholesterol esterification reduces the neurotoxicity of prions.
The transmissible spongiform encephalopathies develop following the conversion of a host-encoded protein (PrP(C)) into abnormally folded, disease-related isoforms (PrP(Sc)). Here we report that three acyl-coenzyme A:cholesterol acyltransferase (ACAT) inhibitors, TMP-153, FR179254 or YIC-C8-434, were more toxic to prion-infected neuronal cell lines (ScGT1 and ScN2a cells) than to their uninfected equivalents (GT1 and N2a cells). The toxicity of ACAT inhibitors for ScGT1 cells was not reversed by the addition of cholesterol esters, rather it was increased by the addition of free cholesterol indicating that the toxicity of ACAT inhibitors was related to the increased free cholesterol content of cells rather than reduced amounts of cholesterol esters. This hypothesis was strengthened by the observation that the addition of free cholesterol killed ScGT1, but not GT1 cells. Treatment with ACAT inhibitors increased caspase-3 activity and prostaglandin E(2) production in ScGT1 cells but not in GT1 cells. The addition of the phospholipase A(2) (PLA(2)) inhibitors (AACOCF(3) or MAFP) reduced prostaglandin E(2) production and protected ScGT1 cells against the toxicity of ACAT inhibitors. These results indicate that cholesterol esterification is an important cellular response that reduces PrP(Sc)-induced activation of PLA(2) and protects against cell death in ScGT1 cells.


Novel Neonatal Umbilical Catheter Protection and Stabilization Device in In vitro Model of Catheterized Human Umbilical Cords: Effect of Material and Venting on Bacterial Colonization.
Umbilical central lines deliver life-saving medications and nutrition for neonates; however, complications associated with umbilical catheters (UCs) occur more frequently than in adults with central lines (i.e., line migration, systemic infection). We have developed a device for neonatal UC protection and stabilization to reduce catheter exposure to bacteria compared with the standard of care: "goal post" tape configuration. This study analyzes the effect of device venting and material on bacterial load of human umbilical cords in vitro. Catheters were inserted into human umbilical cord segments in vitro, secured with plastic or silicone vented prototype versus tape, and levels of bacterial colonization were compared between groups after 7 days of incubation. Nonvented plastic prototype showed increased bacterial load compared with goal post (p = 0.04). Colonization was comparable between the goal post and all vented plastic prototypes (p ≥ 0.30) and when compared with the vented silicone device (p = 1). A novel silicone device does not increase external bacterial colonization compared with the current standard of care for line securement, and may provide a safe, convenient alternative to standard adhesive tape for UC stabilization. Future studies are anticipated to establish safety in vivo, alongside benefits such as migration and infection reduction.


Pancreaticoduodenectomy: Outcomes of a complex surgical procedure from a developing country.
Pancreaticoduodenectomy (PD) plays an integral part in the management of pancreatic, periampullary and duodenal cancers, along with a few other pathologies of this region. Despite advances in surgery PD continues to have significant morbidity and noteworthy mortality. The aim of this study is to provide an in-depth report on the patient characteristics, indications and the outcomes of PD) in a tertiary cancer hospital in Pakistan. The study population included patients who underwent PD between January 1, 2014 and march 31, 2019, at Shaukat Khanum Memorial Cancer Hospital and Research Center (SKMCH&RC) in Pakistan. The data was retrospectively analyzed from the Hospital Information System (HIS), which is a prospectively maintained patient electronic database of SKMCH&RC. Patient characteristics, procedural details and post-operative outcomes according to internationally accepted definitions were reported. A total of 161 patients underwent PD at our hospital in the study period at a median age of 53 years, ranging from 19 to 78 years. 62% of the patients were males while 37% were females. Jaundice was the most common presenting symptom (64.6%), followed by abdominal pain (26.7%). PD with pancreaticogastrostomy was performed in 110 patients (68.3%), while pancreaticojejunostomy was performed in the rest of the cohort. Surgical site infection (SSI) was observed in 64 patients (40%). The incidence of Pancreatic Fistula grade C based on the International Study Group on Pancreatic Fistula (ISGPF) definition was 7.45% (n = 12). The 30 days mortality rate was 3.1%. Median survival of the cohort was 21 ±1.13 months and disease-free survival was 16±2.62 months. PD can be performed with acceptable morbidity and mortality in a resource constrained country, as long as it is undertaken in a high-volume center. This is in keeping with data published from other well-reputed international centers.


4-(1H-imidazo[4,5-f]-1,10-phenanthrolin-2-yl)phenol-based G-quadruplex DNA binding agents: telomerase inhibition, cytotoxicity and DNA-binding studies.
Four novel 4-(1H-imidazo[4,5-f]-1,10-phenanthrolin-2-yl)phenol derivatives 1-4 have been synthesized, and their G-quadruplex DNA-binding interactions, telomerase inhibition, antiproliferative activity, cell cycle arrest, and apoptotic induction were studied. All compounds show the preferential h-telo, c-myc, and c-kit2 G-quadruplex binding affinity and the G-quadruplex versus duplex selectivity. In the case of the same G-quadruplex target, the compound 1 exhibits better stabilization effect (ΔT(m)) than the other three compounds and also gives 80.2% inhibition of telomerase activity at 7.5 μM. All compounds can promote selectively the formation of parallel G-quadruplex structure of both c-myc and c-kit2 without addition of any cations. Four compounds display the cytotoxicity activities against HeLa and HepG2 cells by MTT assay with IC50 values of about 10(-6) and 10(-5) M, respectively, and cause a substantial decrease in the G2/M-phase cell population and a significant increase in the number of apoptotic cells.


Involvement of miR-200b-PKCα signalling in pulmonary hypertension in cor pulmonale model.
The right ventricle (RV) enlargement and pulmonary fibrosis are involved in cor pulmonale. The role of miR-200b in cor pulmonale is less well understood. This study was designed to evaluate the regulatory roles of miR-200b in cor pulmonale. Cor pulmonary mouse model was built via monocrotaline injection of monocrotaline (MCT). The expression of miR-200b in the lungs, RV and left ventricle (LV) are using real-time polymerase chain reaction. The transthoracic echocardiography was employed to determine the effects of miR-200b mimics and Gö6976 injection on MCT mice. The protein levels of protein kinase C α (PKCα), collagen, and fibronectin in the lung, RV, and LV in the mice with and without miR-200b mimics and Gö6976 injection were evaluated using western blot. The expression of miR-200b decreased in MCT mice, while there was no difference in LV. Both the miR-200b mimics and Gö6976 injection reversed the muscularization in the pulmonary artery, reversed RV hypertrophy, reduced RV systolic pressure, wall thickness and pulmonary fibrosis. The injection of miR-200b can reduce the PKCα expression in the lung, RV, and LV. This study confirmed the down-regulation of miR-200b in cor pulmonale. The reverse effects of miR-200b in the present study may provide a potential tool for cor pulmonary treatment.


Successful ablation of frequent atrial premature beats from non-coronary aortic cusp with remote magnetic navigation.
A 59-year-old female with structurally normal heart was admitted to our hospital for treatment of highly symptomatic, drug refractory atrial premature beats (APB). ECG revealed atrial parasystolic trigeminy. The arrhythmogenic focus was mapped and ablated using magnetic remote navigation and 3D electroanatomical mapping system. To our knowledge, this is the first report on successful ablation of frequent APBs in the non-coronary aortic cusp.


[Study of application fertilizer on Aconitum carmichaeli].
To study N, P, K and organic fertilizer on the action of the yield and quality of Aconitum carmichaeli. Four factors quadratic regression rotation combination design and agricultural biological statistics were applicated. The amount and proportion of N, P, K and organic fertilizer had evident influence on the yield and quality of Radix Aconiti Lateralis Preparata. The regression equation really reflected the fact. The application of N 13.04 - 15.13 kg, P 38.70 - 44.34 kg, K 22.50 - 26.46kg and organic fertilizer 1900 - 2200 kg per mu can gain high yield (> or =550 kg/mu) at great possibilities in the experiment.


Higher longitudinal brain white matter atrophy rate in aquaporin-4 IgG-positive NMOSD compared with healthy controls.
We aimed to compare longitudinal brain atrophy in patients with neuromyelitis optica spectrum disorder (NMOSD) with healthy controls (HCs). The atrophy rate in patients with anti-aquaporin-4 antibody-positive NMOSD (AQP4 + NMOSD) was compared with age-sex-matched HCs recruited from the Japanese Alzheimer's Disease Neuroimaging Initiative study and another study performed at Chiba University. Twenty-nine patients with AQP4 + NMOSD and 29 HCs were enrolled in the study. The time between magnetic resonance imaging (MRI) scans was longer in the AQP4 + NMOSD group compared with the HCs (median; 3.2 vs. 2.9 years, P = 0.009). The annualized normalized white matter volume (NWV) atrophy rate was higher in the AQP4 + NMOSD group compared with the HCs (median; 0.37 vs. - 0.14, P = 0.018). The maximum spinal cord lesion length negatively correlated with NWV at baseline MRI in patients with AQP4 + NMOSD (Spearman's rho = - 0.41, P = 0.027). The annualized NWV atrophy rate negatively correlated with the time between initiation of persistent prednisolone usage and baseline MRI in patients with AQP4 + NMOSD (Spearman's rho = - 0.43, P = 0.019). Patients with AQP4 + NMOSD had a greater annualized NWV atrophy rate than HCs. Suppressing disease activity may prevent brain atrophy in patients with AQP4 + NMOSD.


Perspective: A proposal on solutions of modern supply chain construction for lactoferrin.
Lactoferrin is an iron-binding glycoprotein of the transferrin family that is found in most bodily fluids of mammals and has a variety of biological and beneficial functions, with great importance in health enhancement as a supplement for humans and other animals. More than 300 t of lactoferrin were produced in 2021, and this number is expected to grow yearly by 10% to 12%, to over 580 t in 2030. With new and important functions of lactoferrin being revealed and studied, focus on its industrial production and application is increasing accordingly. However, lactoferrin is mainly sourced from cheese whey or skim milk by cation-exchange column chromatography, which is a costly and low-quality method. A potential solution for lactoferrin global supply chain construction is proposed in this article as a complement to traditional routes of purification from whey or skim milk. The large-scale production of lactoferrin, mainly by recombinant yeast, mammal, and grain systems, as well as the market niche and product design, are discussed.


A Comparative Trial of the Effectiveness of Nasal Interfaces Used to Deliver Continuous Positive Airway Pressure for a Brief Period in Infants With Transient Tachypnea of the Newborn.
There is insufficient data on the effectiveness of the interfaces used for nasal continuous airway pressure (nCPAP) in newborn infants. Transpulmonary pressure (PTP) calculated from a measured esophageal pressure (Pes) could be used as a surrogate for the pressure transmitted to the distal airways during nCPAP. We aimed to compare the effectiveness of two nasal interfaces, the nasal mask and bi-nasal short prongs, during a relatively brief period of respiratory support by calculated PTP (cPTP) in infants with transient tachypnea of the newborn (TTN). Newborns with TTN who needed respiratory assistance with nCPAP were randomized to use either bi-nasal short prongs or a nasal mask. Esophageal pressure measurements were done in order to calculate PTP with either interface. The primary outcome was the cPTP transmitted with each nasal interface. Esophageal pressure measurements were recorded and PTP values were calculated from Pes measurements at the 1st, 6th, 12th and 24th hours in each patient as long as the respiratory support lasted. Sixty-two newborns with TTN and on nCPAP were randomized into two groups: Group 1 to use bi-nasal short prongs (n: 31) and Group 2 to use a nasal mask (n: 31). Inspiratory and expiratory Pes and cPTP values at the 1st, 6th, 12th and 24th hours were similar with the two interfaces (P<.05). A nasal mask is similarly effective and safe as bi-nasal short prongs during a brief period of non-invasive respiratory support with nCPAP in late preterm and term neonates with TTN.


In vitro inhibition of histamine release from mouse mast cells and human basophils by an anthranilic acid derivative.
Optimal conditions for in vitro histamine release mediated either by Con A (3 micrograms/ml) or by Ionophore A23187 (1 microgram/ml), were established for mouse peritoneal mast cells and human normal basophils. In both systems N-5' exerts potent inhibiting effects on histamine release after short term (1-5 minutes) in vitro preincubation. At concentrations of 1mM for mouse mast cells and 3mM for normal human basophils, N-5' inhibits up to 95% Con A-induced histamine release and more than 50% ionophore-induced histamine release. Such in vitro effects are more potent than DSCG-mediated inhibition, under similar experimental conditions, and are resistant to challenge with exceeding doses of the two releasing agents, particularly in the Con A system. Interestingly, basophils with apparent normal morphology, from a CML patient, were resistant to both challenges.


The ventralized ogon mutant phenotype is caused by a mutation in the zebrafish homologue of Sizzled, a secreted Frizzled-related protein.
The BMP signaling pathway plays a key role during dorsoventral pattern formation of vertebrate embryos. In zebrafish, all cloned mutants affecting this process are deficient in members of the BMP pathway. In a search for factors differentially expressed in swirl/bmp2b mutants compared with wild type, we isolated zebrafish Sizzled, a member of the secreted Frizzled-related protein family and putative Wnt inhibitor. The knockdown of sizzled using antisense morpholino phenocopied the ventralized mutant ogon (formerly also known as mercedes and short tail). By sequencing and rescue experiments, we demonstrate that ogon encodes sizzled. Overexpression of sizzled, resulting in strongly dorsalized phenotypes, and the expression domains of sizzled in wild type embryos, localized in the ventral side during gastrulation and restricted to the posterior end during segmentation stages, correlate with its role in dorsoventral patterning. The expanded expression domain of sizzled in ogon and chordino together with its downregulation in swirl suggests a BMP2b-dependent negative autoregulation of sizzled. Indicating a novel role for a secreted Frizzled-related protein, we show that, in addition to the BMP pathway, a component of the Wnt signaling pathway is required for dorsoventral pattern formation in zebrafish.


trans-cis Configuration regulated supramolecular polymer gels and chirality transfer based on a bolaamphiphilic histidine and dicarboxylic acids.
Supramolecular polymer gels based on the co-assembly of bolaamphiphilic l-histidine(BolaHis) and dicarboxylic acids are dependent on the molar ratios, flexibility and cis-trans configuration of acid molecules. Thus, oligomerized rigid cis-maleic acid or flexible trans-cyclohexane dicarboxylic acid can form chiral supramolecular polymer gels with l-BolaHis.


Misdiagnosis Among Frequent Exacerbators of Clinically Diagnosed Asthma and COPD in Absence of Confirmation of Airflow Obstruction.
Clinical diagnosis of severe asthma and chronic obstructive lung disease (COPD) remains a challenge and often flawed with lack of objective confirmation of airflow obstruction (AO). Misdiagnosis of asthma and COPD has been reported in stable disease, data are non-existent in frequent exacerbators. We investigated misdiagnosis and its predictors in frequent exacerbators. The cohort comprised of frequent severe exacerbators (requiring ≥2 emergency room (ER) visits or hospitalizations) of physician diagnosed (PD)-asthma and PD-COPD. All patients underwent a rigorous diagnostic algorithm over a follow-up period of 10 ± 6 months. Two board-certified pulmonologists ascertained final diagnosis. Patients with persistent absence of AO were identified to have misdiagnosis. Multivariate logistic regression analyses were used to identify predictors of misdiagnoses. Among 333 frequent exacerbators analyzed (171 patients with PD-asthma, 162 with PD-COPD, mean annual exacerbations 3.4 ± 2.8), 24 % of patients had a baseline post-bronchodilator spirometry. Misdiagnosis was found in 26 % (87 of 333) of patients. Another 12 % (41 of 333) of patients had obstructive lung diseases other than asthma and COPD. Independent risk factors for misdiagnosis were spirometry underutilization (PD-asthma: OR = 2.8, 95 % CI 1.16-6.78, p = 0.02 and PD-COPD: OR = 10.7, 95 % CI 2.05-56.27, p = 0.005) and pack years of smoking (PD-COPD: OR = 1.05, 95 % CI 1.01-1.11, p = 0.03). Objective confirmation of AO is essential in preventing misdiagnosis in frequent severe exacerbators of clinically diagnosed asthma and COPD, a third of whom have neither. Spirometry utilization is strongly associated with a reduced risk of misdiagnosis. Smoking is associated with increased risk of misdiagnosis in severe COPD, but not asthma.


Roles of the HIF-1α pathway in the development and progression of keloids.
Keloids, a pathological scar that is induced by the consequence of aberrant wound healing, is still a major global health concern for its unsatisfactory treatment outcomes. HIF-1α, a main regulator of hypoxia, mainly acts through some proteins or signaling pathways and plays important roles in a variety of biological processes. Accumulating evidence has shown that HIF-1α played a crucial role in the process of keloid formation. In this review, we attempted to summarize the current knowledge on the association between HIF-1α expression and the development and progression of keloids. Through a comprehensive analysis, the molecular mechanisms underlying HIF-1α in keloids were shown to be correlated to the proliferation of fibroblasts, angiogenesis, and collagen deposits. The affected proteins and the signaling pathways were multiple. For instance, HIF-1α was reported to promote keloids formation by enhancing angiogenesis, fibroblast proliferation, and collagen deposition through the activation of periostin PI3K/Akt, TGF-β/Smad and TLR4/MyD88/NF-κB pathway. However, the specific effects of HIF-1α on keloids keloid illnesses in clinical practice is are entirely unclear, and further studies in clinical trials are still warranted. Therefore, an in-depth understanding of the biological mechanisms of HIF-1α in keloid formation is significant to develop promising therapeutic targets for the treatment of keloids in clinical practice.


Sensitive colorimetric assays for α-glucosidase activity and inhibitor screening based on unmodified gold nanoparticles.
A colorimetric sensor has been developed in this work to sensitively detect α-glucosidase activity and screen α-glucosidase inhibitors (AGIs) utilizing unmodified gold nanoparticles (AuNPs). The sensing strategy is based on triple-catalytic reaction triggered by α-glucosidase. In the presence of α-glucosidase, aggregation of AuNPs is prohibited due to the oxidation of cysteine to cystine in the system. However, with addition of AGIs, cysteine induced aggregation of AuNPs occurs. Thus, a new method for α-glucosidase activity detection and AGIs screening is developed by measuring the UV-vis absorption or visually distinguishing. A well linear relation is presented in a range of 0.0025-0.05 U mL(-1). The detection limit is found to be 0.001 U mL(-1) for α-glucosidase assay, which is one order of magnitude lower than other reports. The IC50 values of four kinds of inhibitors observed with this method are in accordance with other reports. The using of unmodified AuNPs in this work avoids the complicated and time-consuming modification procedure. This simple and efficient colorimetric method can also be extended to other enzymes assays.


Tophaceous gout in the elderly: a clinical case review.
Gout is the most common cause of arthritis in the elderly. Its incidence among older people has risen worldwide due to an increase in risk factors such as renal diseases, metabolic syndrome, and a diet rich in purines. In older age, tophaceous gout may affect different joints from its classical presentation, due to other concomitant musculoskeletal diseases, but specific data on its epidemiology and clinical aspects in the elderly are limited to a few case reports. The present review focuses on the distinctive aspects of tophaceous gout in the elderly, revisiting all our clinical cases seen from 1990 to December 2011. Our findings indicate that: tophaceous gout can affect several joints in the elderly, including some unusual sites; its incidence is similar in both genders in the elderly even if the latency period between its initial diagnosis and the onset of tophi is higher in men; and vertebral localizations are rising and often solitary. The components of metabolic syndrome are the most common medical conditions associated with tophaceous gout. In conclusion, tophaceous gout in the elderly may be a growing medical problem and cause of disability in years, partly because of the new sites involved.


Loss of myeloid Tsc2 predisposes to angiotensin II-induced aortic aneurysm formation in mice.
Genetic studies have proved the involvement of Tuberous sclerosis complex subunit 2 (Tsc2) in aortic aneurysm. However, the exact role of macrophage Tsc2 in the vascular system remains unclear. Here, we examined the potential function of macrophage Tsc2 in the development of aortic remodeling and aortic aneurysms. Conditional gene knockout strategy combined with histology and whole-transcriptomic analysis showed that Tsc2 deficiency in macrophages aggravated the progression of aortic aneurysms along with an upregulation of proinflammatory cytokines and matrix metallopeptidase-9 in the angiotensin II-induced mouse model. G protein-coupled receptor 68 (Gpr68), a proton-sensing receptor for detecting the extracellular acidic pH, was identified as the most up-regulated gene in Tsc2 deficient macrophages compared with control macrophages. Additionally, Tsc2 deficient macrophages displayed higher glycolysis and glycolytic inhibitor 2-deoxy-D-glucose treatment partially attenuated the level of Gpr68. We further demonstrated an Tsc2-Gpr68-CREB network in macrophages that regulates the inflammatory response, proteolytic degradation and vascular homeostasis. Gpr68 inhibition largely abrogated the progression of aortic aneurysms caused by Tsc2 deficiency in macrophages. The findings reveal that Tsc2 deficiency in macrophages contributes to aortic aneurysm formation, at least in part, by upregulating Gpr68 expression, which subsequently drives proinflammatory processes and matrix metallopeptidase activation. The data also provide a novel therapeutic strategy to limit the progression of the aneurysm resulting from Tsc2 mutations.


Comparative chromosomal studies on two minnow fish, Phoxinus phoxinus (Linnaeus, 1758) and Eupallasella perenurus (Pallas, 1814); an associated cytogenetic-taxonomic considerations.
The present work provides new data on the banding pattern of two cyprinid fish species Phoxinus phoxinus and Eupallasella perenurus from Poland. C-banding, silver-staining (Ag), and fluorescent staining with chromomycin A3 techniques were used to describe the karyotypes. Both of the species karyotypes of 2n = 50 were characterised by one pair of acrocentric chromosomes, the largest in the set, and by two pairs of NOR-bearing chromosomes. In the chromosome set of Ph. phoxinus Ag-stained NORs were located on telomeres of two metacentric and two submetacentric chromosomes, but in most metaphases only one of the two homologous was observed. The karyotype of E. perenurus was characterised by Ag-NOR regions at a telomeric position on the shorter arm of two submetacentric chromosome pairs. In most metaphases only three NOR-bearing chromosomes were observed. In both investigated species the location of the A3 positive signals corresponded with the location of Ag-stained NORs and these sites were associated with heterochromatin shown as C-bands. The results of cytogenetical studies on other related, mainly the North American phoxinins, species are compared and discussed.


Invasive Alien Slug Arion vulgaris Moquin-Tandon, 1855 (Gastropoda: Pulmonata: Arionidae) in Moscow Parks and Its Co-introduced Parasite Alloionema appendiculatum Schneider, 1859.
The present study investigates the origin of Arion vulgaris slugs in the parks of Moscow city and their parasites. Snails and slugs inhabiting green areas of Moscow city were collected in the summer season of 2020 and examined on the presence of gastropod-associated nematodes and trematodes using morphological and molecular methods. The presence of the alien slug species, Arion vulgaris, was recorded in several locations, and the mitochondrial gene-based analysis has shown that slug populations inhabited Moscow parks originated from West and Central Europe. Out of a total of 15 gastropod species examined, A. vulgaris was the only species infected by the nematode Alloionema appendiculatum Schneider, 1859, a larval parasite of molluscs. It is the first record of this nematode from the territory of the Russian Federation. COX1 mtDNA sequences of A. appendiculatum obtained from 3 populations of infected slugs were identical with those from Western and Central Europe similarly to their gastropod hosts thus indicating that the nematodes travelled with their hosts. No parasites dangerous for humans or animals were found. The complex life cycle of A. appendiculatum includes a free-living stage in soil which offers a source of infection for other potentially susceptible gastropod species but the capacity of A. appendiculatum to change hosts in local conditions needs to be further investigated. The particular susceptibility and tolerance of A. vulgaris to nematodes in our study was in concordance with earlier data while in contradiction with the enemy release hypothesis.


A seasonal simulation approach for culture depth influence on the temperature for different characterized microalgae strains.
Irradiance and temperature are among the most important variables that affect microalgae growth, being both difficult to control in outdoor raceway reactors utilized for large-scale production of microalgae biomass. They are mainly a function of the location of the reactors, thus, producing certain strains of microalgae in inappropriate places conduces to the failure of the systems. To be able to determine important parameters of any microalgae strains on the performance of the culture, such as the influence of irradiance and temperature, is a powerful tool in decision-making processes. In addition, whatever the strain and location, operation strategies must be defined for each specific case, such as the imposed dilution rate and culture depth, both influencing the light availability and temperature of the culture as major variables determining the biomass productivity. In this paper, a simulation-based methodology is proposed to establish the influence of season and culture depth on the 1-year age irradiance and temperature of the culture, and thus on the biomass productivity of different microalgae strains. Up to five of the most frequently produced strains, such as Spirulina platensis, Chlorella vulgaris, Nannochloropsis gaditana, Isochrysis galbana, and Scenedesmus almeriensis have been considered. The challenge is to develop an easy-to-manage decision-making tool for the optimal design and operation of large-scale microalgae facilities. Especially, dates for microalgae production and culture depth at which the reactors must be operated will be provided, being valid for any microalgae strain. The proposed methodology will largely contribute to the risk of investment in this field, then to enlarge the relevance of the microalgae production industry.


Dynamic changes in circulating EBV-DNA load during treatment have prognostic values in EBV+ DLBCL-NOS: a Chinese cohort study.
EBV-positive diffuse large B-cell lymphoma, not otherwise specified (EBV+ DLBCL-NOS), is an EBV-positive clonal B-cell lymphoid proliferation and circulating EBV-DNA is a great indicator for prognosis among EBV associated disease. In this retrospective study, we report 66 EBV+ DLBCL cases among 2137 DLBCL-NOS cases diagnosed from 2013 to 2021 (prevalence of 6.0%). After a median follow-up of 27 months, progression-free survival (PFS) and overall survival (OS) at 2 years were 39.5% ± 6.2% and 53.6% ± 6.4%, respectively. Multivariate analysis showed that only the biomarker of the positivity of post treatment EBV-DNA had a borderline correlation with shorter PFS and OS (PFS: P = 0.053; OS: P = 0.065). Patients were divided into three subgroups according to dynamic changes of EBV-DNA status: EBV-DNA persistently negative group, EBV-DNA persistently positive group, and EBV-DNA transformed from positive to negative group; among the three groups, patients of the persistently positive group had worst PFS and OS (P = 0.0527 and P = 0.0139, respectively). Decline in EBV copies correlated significantly with treatment response as well. In conclusion, circulating EBV-DNA level played a vital role in prognostic and monitoring marker for EBV+ DLBCL-NOS.


Dataset of forest landowner survey to assess interest in supplying woody biomass in two Southeastern United States fuelsheds.
This article presents data from a recent mail survey of forest landowners regarding their land ownership characteristics and motivations, past and future management activities, and owner perceptions of bioenergy and its impact on forests. The data presented in this article are related to the research article entitled 'Opportunities and Attitudes of Private Forest Landowners in Supplying Woody Biomass for Renewable Energy' [1]. The survey was conducted in the Atlantic Coastal Plain of the United States, where two primary ports exporting wood pellets to Europe are located. Specifically, the data include responses on forest characteristics, forest management activities, knowledge and interest in woody biomass for energy production, and sociodemographic variables. Additionally, landowner decisions for supplying wood for traditional forest products and biomass for energy were modeled. More than 2900 forest landowners were contacted, with 707 owners providing completed surveys.


Toll-like receptors and innate antiviral responses.
Toll-like receptors (TLRs) have a unique and important role in detecting the presence of pathogenic infection. TLRs can recognize conserved structures from a wide variety of microorganisms, such as bacteria, mycobacteria, spirochetes and yeast. However, they are generally not thought to play a major role in viral infection. Several reports have now identified distinct viral ligands for the TLRs, and evidence is accumulating for a functional role of the TLRs in mediating antiviral effector mechanisms.


Nur77 nuclear import and its NBRE-binding activity in thymic lymphoma cells are regulated by different mechanisms sensitive to FK506 or HA1004.
Thymic lymphoma cells restore their sensitivity to ionomycin-induced apoptosis when treated with FK506 or HA1004. In apoptosis-resistant cells, ionomycin-induced Nur77 strongly binds DNA during the first 2 h of response, in contrast to lymphoma cells treated with ionomycin together with FK506 or HA1004, which undergo massive apoptosis. We show that Nur77 could discriminate between calcium signals sensitive to FK506 and those sensitive to HA1004, as the inhibitors differentially regulate the kinetics of Nur77 nuclear import, and FK506, unlike HA1004, inhibits Nur77 DNA-binding activity. In the presence of HA1004, NBRE binding by Nur77 protein increases with time (6 h vs 2 h), whereas the final outcome of both inhibitors is apoptosis of thymic lymphoma cells.


Singapore grouper iridovirus VP122 targets grouper STING to evade the interferon immune response.
Singapore grouper iridovirus (SGIV) is a highly pathogenic Iridoviridae that causes hemorrhage and spleen enlargement in grouper. Despite previous genome annotation efforts, many open reading frames (ORFs) in SGIV remain uncharacterized, with largely unknown functions. In this study, we identified the protein encoded by SGIV ORF122, now referred to as VP122. Notably, overexpression of VP122 promoted SGIV replication. Moreover, VP122 exhibited antagonistic effects on the natural antiviral immune response through the cGAS-STING signaling pathway. It specifically inhibited the cGAS-STING-triggered transcription of various immune-related genes, including IFN1, IFN2, ISG15, ISG56, PKR, and TNF-α in GS cells. Additionally, VP122 significantly inhibited the activation of the ISRE promoter mediated by EccGAS and EcSTING but had no effect on EccGAS or EcSTING alone. Immunoprecipitation and Western blotting experiments revealed that VP122 specifically interacts with EcSTING but not EccGAS. Notably, this interaction between VP122 and EcSTING was independent of any specific domain of EcSTING. Furthermore, VP122 inhibited the self-interaction of EcSTING. Interestingly, VP122 did not affect the recruitment of EcTBK1 and EcIRF3 to the EcSTING complex. Collectively, our results demonstrate that SGIV VP122 targets EcSTING to evade the type I interferon immune response, revealing a crucial role for VP122 in modulating the host-virus interaction.


Molecular investigation of adequate sources of mesenchymal stem cells for cell therapy of COVID-19-associated organ failure.
The use of mesenchymal stem cells (MSC) derived from several sources has been suggested as a major anti-inflammation strategy during the recent outbreak of coronavirus-19 (COVID-19). As the virus enters the target cells through the receptor ACE2, it is important to determine if the MSC population transfused to patients could also be a target for the virus entry. We report here that ACE2 is highly expressed in adult bone marrow, adipose tissue, or umbilical cord-derived MSC. On the other hand, placenta-derived MSC express low levels of ACE2 but only in early passages of cultures. MSC derived from human embryonic stem cell or human induced pluripotent stem cells express also very low levels of ACE2. The transcriptome analysis of the MSCs with lowest expression of ACE2 in fetal-like MSCs is found to be associated in particularly with an anti-inflammatory signature. These results are of major interest for designing future clinical MSC-based stem cell therapies for severe COVID-19 infections.


Hyponatremia in the prognosis of acute ischemic stroke.
Hyponatremia is a risk factor for stroke and cardiovascular disease. Even mild hyponatremia is associated with increased 30-day mortality after myocardial infarction, and it has recently shown to increase the 3-year mortality after a stroke. In this work, we investigated both acute and chronic clinical outcomes after a stroke in hyponatremic patients. We reviewed all patients admitted between 2004 and 2011 with the diagnosis of acute ischemic stroke. Hyponatremia was defined as serum sodium level less than 135 mmol/L and recorded on admission. All hemorrhagic strokes were excluded. Data were analyzed using multivariate logistic regression. A total of 3585 patients with stroke were identified. Hyponatremia was observed in 565 (16%) patients. Baseline characteristics were similar between groups except heart failure (P = .015), cancer (P = .038), diabetes (P < .001), and dementia (P = .015). Hyponatremic patients had higher National Institutes of Health Stroke Scale (NIHSS) score on admission (P = .032) and at discharge (P = .02). Despite similar modified Barthel Index (mBI) preadmission, patients with hyponatremia had worse mBI on admission (P = .049). Hyponatremia was associated with higher mortality in hospital (P = .039) and at 3-month (P = .001) and 12-month follow-ups (P = .001). A poorer discharge disposition was seen in the hyponatremia group (P = .004). Complications during admission were similar between groups except for urinary infection (P = .008). Patients with hyponatremia had worse NIHSS and mBI values on admission, and their deficits worsened during their hospitalization. This is the first study to demonstrate that hyponatremia is associated with acute mortality and poorer discharge dispositions and to confirm that higher mortality occurs in these patients, even after 12 months after a stroke.


Patient-reported mental health and well-being trajectories in oncology patients during radiation therapy: an exploratory retrospective cohort analysis using the Ontario Cancer Registry.
Mental health and well-being trajectories are not expected to be homogeneous in diverse clinical populations. This exploratory study aims to identify subgroups of patients with cancer receiving radiation therapy who have different mental health and well-being trajectories, and examine which socio-demographic, physical symptoms, and clinical variables are associated with such trajectories. Retrospective analysis of radiation therapy patients diagnosed with cancer in 2017 was conducted using data from the Ontario Cancer Registry (Canada) and linked with administrative health data. Mental health and well-being were measured using items from the Edmonton Symptom Assessment System-revised questionnaire. Patients completed up to 6 repeated measurements. We used latent class growth mixture models to identify heterogeneous mental health trajectories of anxiety, depression, and well-being. Bivariate multinomial logistic regressions were conducted to explore variables associated with the latent classes (subgroups). The cohort (N = 3416) with a mean age of 64.5 years consisted of 51.7% females. Respiratory cancer was the most common diagnosis (30.4%) with moderate to severe comorbidity burden. Four latent classes with distinct anxiety, depression, and well-being trajectories were identified. Decreasing mental health and well-being trajectories are associated with being female; living in neighborhoods with lower income, greater population density, and higher proportion of foreign-born individuals; and having higher comorbidity burden. The findings highlight the importance of considering social determinants of mental health and well-being, in addition to symptoms and clinical variables, when providing care for patients undergoing radiation therapy.


The HIF1α/HIF2α-miR210-3p network regulates glioblastoma cell proliferation, dedifferentiation and chemoresistance through EGF under hypoxic conditions.
Hypoxia-inducible factor 1α (HIF1α) promotes the malignant progression of glioblastoma under hypoxic conditions, leading to a poor prognosis for patients with glioblastoma; however, none of the therapies targeting HIF1α in glioblastoma have successfully eradicated the tumour. Therefore, we focused on the reason and found that treatments targeting HIF1α and HIF2α simultaneously increased tumour volume, but the combination of HIF1α/HIF2α-targeted therapies with temozolomide (TMZ) reduced tumourigenesis and significantly improved chemosensitization. Moreover, miR-210-3p induced HIF1α expression but inhibited HIF2α expression, suggesting that miR-210-3p regulates HIF1α/HIF2α expression. Epidermal growth factor (EGF) has been shown to upregulate HIF1α expression under hypoxic conditions. However, in the present study, in addition to the signalling pathways mentioned above, the upstream proteins HIF1α and HIF2α have been shown to induce EGF expression by binding to the sequences AGGCGTGG and GGGCGTGG. Briefly, in a hypoxic microenvironment the HIF1α/HIF2α-miR210-3p network promotes the malignant progression of glioblastoma through a positive feedback loop with EGF. Additionally, differentiated glioblastoma cells underwent dedifferentiation to produce glioma stem cells under hypoxic conditions, and simultaneous knockout of HIF1α and HIF2α inhibited cell cycle arrest but promoted proliferation with decreased stemness, promoting glioblastoma cell chemosensitization. In summary, both HIF1α and HIF2α regulate glioblastoma cell proliferation, dedifferentiation and chemoresistance through a specific pathway, which is important for glioblastoma treatments.


Reduced lipolysis in lipoma phenocopies lipid accumulation in obesity.
Elucidation of lipid metabolism and accumulation mechanisms is of paramount importance to understanding obesity and unveiling therapeutic targets. In vitro cell models have been extensively used for these purposes, yet, they do not entirely reflect the in vivo setup. Conventional lipomas, characterized by the presence of mature adipocytes and increased adipogenesis, could overcome the drawbacks of cell cultures. Also, they have the unique advantage of easily accessible matched controls in the form of subcutaneous adipose tissue (SAT) from the same individual. We aimed to determine whether lipomas are a good model to understand lipid accumulation. We histologically compared lipomas and control SAT, followed by assessment of the lipidome using high-resolution 1H NMR spectroscopy and ESI-IT mass spectrometry. RNA-sequencing was used to obtain the transcriptome of lipomas and the matched SAT. We found a significant increase of small-size (maximal axis < 70 µm) and very big (maximal axis > 150 µm) adipocytes within lipomas. This suggests both enhanced adipocyte proliferation and increased lipid accumulation. We further show that there is no significant change in the lipid composition compared to matched SAT. To better delineate the pathophysiology of lipid accumulation, we considered two groups with different genetic backgrounds: (1) lipomas with HMGA2 fusions and (2) without gene fusions. To reduce the search space for genes that are relevant for lipid pathophysiology, we focused on the overlapping differentially expressed (DE) genes between the two groups. Gene Ontology analysis revealed that DE genes are enriched in pathways related to lipid accumulation. We show that the common shared lipid accumulation mechanism in lipoma is a reduction in lipolysis, with most gene dysregulations leading to a reduced cAMP in the adipocyte. Superficial lipomas could thus be used as a model for lipid accumulation through altered lipolysis as found in obese patients.


Primary pulmonary hypoplasia in the neonate.
Infants with primary pulmonary hypoplasia with respiratory distress immediately after birth, but usually elude early diagnosis. They have no other abnormalities, but frequently develop signs and symptoms of the PFC syndrome. Roentgenographically, they show small, clear lungs and are prone to develop complicating pneumothoraces. The clinical, roentgenographic, and pathologic features of eight infants with primary pulmonary hypoplasia are presented.


A Subset of Polysaccharide Capsules in the Human Symbiont Bacteroides thetaiotaomicron Promote Increased Competitive Fitness in the Mouse Gut.
Capsular polysaccharides (CPSs) play multiple roles in protecting bacteria from host and environmental factors, and many commensal bacteria can produce multiple capsule types. To better understand the roles of different CPSs in competitive intestinal colonization, we individually expressed the eight different capsules of the human gut symbiont Bacteroides thetaiotaomicron. Certain CPSs were most advantageous in vivo, and increased anti-CPS immunoglobulin A correlated with increased fitness of a strain expressing one particular capsule, CPS5, suggesting that it promotes avoidance of adaptive immunity. A strain with the ability to switch between multiple capsules was more competitive than those expressing any single capsule except CPS5. After antibiotic perturbation, only the wild-type, capsule-switching strain remained in the gut, shifting to prominent expression of CPS5 only in mice with intact adaptive immunity. These data suggest that different capsules equip mutualistic gut bacteria with the ability to thrive in various niches, including those influenced by immune responses and antibiotic perturbations.


The Menu Workbench: an automatic menu generator for bio-medical programs.
A program development tool, The Menu Workbench, is described and applied to the computer screen architecture, menu design, and program management of bio-medical programs. Prerequisites for the approach to these problems are presented. An intuitive screen menu system, developed for the program, Immuno-Ligand Analysis System (ILAS), is described in the text. Standardized screen layout and keyboard interaction is explained. The programming of this system of menus was automated with the program, Menu Workbench, in the Turbo PASCAL language in PCDOS, MSDOS and CP/M operating systems. Use of the Menu Workbench program in other bio-medical applications is discussed.


Aerobic bioreactors: condensers, evaporation rates, scale-up and scale-down.
Hydrodynamics, mixing and shear are terms often used when explaining or modelling scale differences, but other scale differences, such as evaporation, can arise from non-hydrodynamic factors that can be managed with some awareness and effort. We present an engineering approach to the prediction of evaporation rates in bioreactors based on gH2O/Nm3 of air entering and leaving the bioreactor and confirm its usefulness in a 28-run design of experiments investigating the effects of aeration rate (0.02 to 2.0 VVM), condenser temperature (10 to 20 °C), fill (2.5 to 5 kg), broth temperature (25 to 40 °C) and agitator speed (25 to 800 rpm). Aeration rate and condenser temperature used in the engineering prediction provided a practically useful estimate of evaporation; the other factors, while statistically identified as having some influence, were of negligible practical usefulness. Evaporation rates were never found to be zero, and could be at least 10% different to those expected at scale. An assessment of evaporation rates for any project is encouraged, and it is recommended that the effects are accounted for by measurements, modelling or by tuning the exhaust cooling device temperature to minimize scale differences.


High quality and fast compressed sensing MRI reconstruction via edge-enhanced dual discriminator generative adversarial network.
Generative adversarial networks (GAN) are widely used for fast compressed sensing magnetic resonance imaging (CSMRI) reconstruction. However, most existing methods are difficult to make an effective trade-off between abstract global high-level features and edge features. It easily causes problems, such as significant remaining aliasing artifacts and clearly over-smoothed reconstruction details. To tackle these issues, we propose a novel edge-enhanced dual discriminator generative adversarial network architecture called EDDGAN for CSMRI reconstruction with high quality. In this model, we extract effective edge features by fusing edge information from different depths. Then, leveraging the relationship between abstract global high-level features and edge features, a three-player game is introduced to control the hallucination of details and stabilize the training process. The resulting EDDGAN can offer more focus on edge restoration and de-aliasing. Extensive experimental results demonstrate that our method consistently outperforms state-of-the-art methods and obtains reconstructed images with rich edge details. In addition, our method also shows remarkable generalization, and its time consumption for each 256 × 256 image reconstruction is approximately 8.39 ms.


Moisture wicking textiles with hydrophilic oriented polyacrylonitrile layer: Enabling ultrafast directional water transport.
Functional textiles with high-performance directional water transport for regulating human sweat are in high demand because of growing concerns about the role of comfort in the performance of wearer. However, the fabrication of such materials remains a critical job. Here, we report a facile strategy to develop hydrophilic oriented polyacrylonitrile (HOPAN)/hydrophilic polylactic acid @polyvinylidene fluoride (HPLA@PVDF) composite membrane with surface energy gradient for enhanced directional water transport. Three step fabrication strategy involves electrospinning of oriented polyacrylonitrile (OPAN fibers) on polylactic acid (PLA) nonwoven surface followed by dip-coating in hydrophilic agent, and single-side electrospray of PVDF dilute solution on HOPAN/HPLA. Combination of highly oriented fiber structure, differential pore size and asymmetric wettability between two layers enabled instant water transport. The resultant fabricated composite membranes offer superior properties with one-way transport capacity (R) of 1117%, overall moisture management capacity (OMMC) of 0.91, and excellent water vapor transmission rate of 11.6 kg m-2 d-1. The successful preparation of these fascinating directional water transport materials offers new insight into the role of fiber alignment along with differential apertures and asymmetric chemical structure for realizing membranes for quick-drying applications.


The molecular basis of enzyme secretion.
Acinar cells are one of the best studied models of exocytotic secretion. A number of different hormones and neurotransmitters interact with specific membrane receptors, and it is commonly held that pancreatic secretagogues stimulate enzyme release via the elevation of either cytosolic free Ca2+ or cellular cyclic adenosine monophosphate. The discovery of the pivotal role played by phospholipid metabolism in the chain of events leading to secretion, together with the introduction of sensitive techniques to monitor cytosolic free Ca2+, has generated a series of studies that have challenged this classical model. Thus, several observations in pancreatic acini as well as other cell types have argued against the notion that a generalized increase in cytosolic free Ca2+ represents a sufficient and necessary stimulus for exocytosis in nonexcitable cells. Furthermore, the demonstration that a single agonist activates multiple transduction pathways has served to refute the schematic view that receptor agonists activate only one second messenger system. The aim of this article is to review the recent advances in understanding the molecular and cellular mechanisms of signal transduction, with particular emphasis on the inositol lipid pathway, and to integrate this information into a new working model of enzyme secretion from acinar cells.


Pharmacological activities of acetal derivatives of hemicholinium no. 3.
Acetal derivatives of hemicholinium no. 3 (HC-3) were synthesized and their chemical structures were confirmed by spectrophotometric evidence and elemental analysis. The acetals elicited a biphasic pattern of neuromuscular inhibition in the cat: (a) an immediate inhibition (early phase block) was judged to be curare-like as responses to acetylcholine (close i.a.) were abolished by acetal administration and reversal of inhibition was effected by neostigmine (25 micrograms/kg); (b) a slow, progressive inhibition of transmission (late phase block) was considered HC-3-like as it occurred only during high frequency stimulation and was antagonized by small doses of choline (1--3 mg/kg). In comparison to HC-3, significanlty greater curare-like activity was noted following acetal administration in vivo and in vitro. Mouse toxicity and cat nerve--muscle studies revealed the acetals to be HC-3-like but 1/2 to 1/3 as active as the parent compound. Cholinesterase inhibition by HC-3 and the acetals was low (I50 greater than 0.1 mM) and did not account for differences in activities. Acetal-elicited hypotension in the cat was attributed to postsynaptic ganglionic blockade and histamine release. Studies employing the 14C-(N-methyl) acetals furnished no evidence of the bioactivation (O-dealkylation) of the acetals to HC-3 in the cat in vivo or in cat liver in vitro. Chromatographic analysis afforded no evidence of molecular modifications of 14C-HC-3 or of the 14C-acetals in these systems.