YAP promotes autophagy and progression of gliomas via upregulating HMGB1.
Due to the hypoxia and nutrient deficiency microenvironment, glioblastoma (GBM) exhibits high autophagy activity and autophagy plays an important role in the progression of GBM. However, the molecular mechanism of autophagy in GBM progression remains unclear. The aim of this study is to delve out the role and mechanism of yes-associated protein (YAP) in GBM autophagy and progression. The level of autophagy or autophagy flux were assessed by using western blotting, GFP-LC3 puncta (Live) imaging, transmission electron microscopy and GFP-RFP-LC3 assay. The GBM progression was detected by using CCK8, EdU, nude mouse xenograft and Ki67 staining. Isobaric tags for relative and absolute quantification (iTraq) quantitative proteomics was used to find out the mediator of YAP in autophagy. Expression levels of YAP and HMGB1 in tissue samples from GBM patients were examined by Western blotting, tissue microarray and immunohistochemistry. YAP over-expression enhanced glioma cell autophagy under basal and induced conditions. In addition, blocking autophagy by chloroquine abolished the promoting effect of YAP on glioma growth. Mechanistically, YAP over-expression promoted the transcription and translocation of high mobility group box 1(HMGB1), a well-known regulator of autophagy, from nucleus to cytoplasm. Down-regulation of HMGB1 abolished the promoting effect of YAP on autophagy and glioma growth. Furthermore, the expression of YAP and HMGB1 were positively associated with each other and suggested poor prognosis for clinical GBM. YAP promoted glioma progression by enhancing HMGB1-mediated autophagy, indicating that YAP-HMGB1 axis was a feasible therapeutic target for GBM. Our study revealed a clinical opportunity involving the combination of chemo-radiotherapy with pharmacological autophagy inhibition for treating GBM patients with YAP high expression.


Emetic potentials of newly identified staphylococcal enterotoxin-like toxins.
Staphylococcal enterotoxins (SEs) are a common causative agent of food poisoning. Recently, many new SE-like (SEl) toxins have been reported, although the role of SEls in food poisoning remains unclear. In this study, the emetic potentials of SElK, SElL, SElM, SElN, SElO, SElP, and SElQ were assessed using a monkey-feeding assay. All the SEls that were tested induced emetic reactions in monkeys at a dose of 100 μg/kg, although the numbers of affected monkeys were significantly smaller than the numbers that were affected after consuming SEA or SEB. This result suggests that these new SEs may play some role in staphylococcal food poisoning.


[Comparative morphology of the two type's hair cells from saccule and utricle under inverted phase contrast microscope].
To explore more reliable standards for identifying vestibular hair cells of saccule and utricle prepared in studies with patch clamp technique under inverted phase contrast microscope. The length and width of two type's hair cell's were measured besides the length of cilia, and all datas were analyzed statistically. The width and length of cilia of two types hair cells in saccule and utricle from guinea pig were similar. The length of type I was longer than that of type II, so the ratio between length and width was larger and the ratio of the length between cilia and cell body was small. Two type's hair cells of saccule and utricle from guinea pig may be distinguished through the ratio of cell body's length and width even the ratio of the length between cilia and cell body, besides the standards before.


Antioxidant and pro-oxidant properties of chlorhexidine and its interaction with calcium hydroxide solutions.
To evaluate the antioxidant and pro-oxidant properties of chlorhexidine (CHX). The scavenging and generation of reactive oxygen species (ROS) by CHX in the presence or absence of saturated Ca(OH)(2) solutions was evaluated. The reaction emitted chemiluminescence in the presence of lucigenin thus was determined by a luminometer to evaluate the levels of ROS production. Changes in DNA conformation were analysed by agarose gel electrophoresis. Paired Student's t-test was used to compare the difference between groups. Chlorhexidine (0.00002-0.02%) effectively scavenged 56-88% of the superoxide radicals generated by the xanthine/xanthine oxidase reaction. Through analysis of PUC18 DNA conformation changes, CHX was shown to be a mild scavenger of hydroxyl radicals generated by H(2)O(2) plus FeCl(2). However, CHX (>0.083%) decreased the mobility of PUC18 plasmid DNA with potential production of DNA-DNA cross-link and severe DNA breaks (presence of DNA smear) at further higher concentrations. Furthermore, CHX induced ROS production including H(2)O(2) and superoxide radicals in 0.1N NaOH (pH = 12.76) or Ca(OH)(2) (pH = 12.5) solutions. Chlorhexidine exhibited both antioxidant and pro-oxidant properties under different conditions. These events are possibly involved in the killing of root canal and periodontal microorganisms when CHX and Ca(OH)(2) were used in combination or separately. Potential genotoxicity and tissue damage when extruded into the periradicular tissue and at higher concentrations should be considered during periodontal and endodontic practice.


Theory of the omega(-4/3) law of the power spectrum in dissipative flows.
It is demonstrated that omega(-4/3) law of the power spectrum, with the angular frequency omega in dissipative flows, is produced by the emission of dispersive waves from the antikink of an congested domain. The analytic theory predicts that the spectrum is proportional to omega(-2) for relatively low frequency and omega(-4/3) for high frequency.


A prospective evaluation of penile measures and glans penis sensory changes after penile prosthetic surgery.
With better designed devices and lower infection rates, satisfaction with inflatable penile prosthesis (IPP) placement is increasingly high. However, dissatisfaction is still present and there is disagreement regarding length and sensation changes after the IPP placement. The aim of this study was to evaluate changes in penile length, girth and sensitivity after IPP placement. From August 2012 to January 2013 all patients undergoing "de novo" IPP surgery were invited to participate in this study. Eighty six patients met inclusion criteria while 62 agreed to participate in this observational study. A week before surgery, penile length and circumference, and glans/elbow biothesiometer readings were recorded 15 minutes after Trimix induced erection. Same measures were taken at postoperative week 6 and month 6. Amperage from Glans biothesiometer readings showed statistically significant shorter readings than elbow biothesiometer preoperatively, 6 weeks and 6 months after surgery (P<0.001 each). No significant sensory difference in the glans penis after IPP was noted. However, compared to preoperative Trimix induced erections, penile length and circumference were greater after IPP placement (P=0.04 and P=0.001, respectively). We observed statistically significant increase in penile length and girth after IPP placement without significant changes in sensory conduction.


Caesarean section following the Fontan procedure: two different deliveries and different anaesthetic choices in the same patient.
The Fontan procedure is performed for patients with a hypoplastic right ventricle, and pregnancies following this palliative surgery are likely to increase. We present a parturient with the Fontan physiology who successfully underwent two consecutive caesarean deliveries; the first under general anaesthesia for emergency surgery and the second under regional anaesthesia for elective surgery. We suggest that pregnancy and delivery do not typically adversely affect maternal cardiac status in these patients. Attention must be paid, however, to fetal loss, prematurity, growth retardation and associated cardiac congenital malformations for which insufficient data exist in the literature in this patient population.


PAD4-dependent antibiosis contributes to the ssi2-conferred hyper-resistance to the green peach aphid.
Myzus persicae, commonly known as green peach aphid (GPA), is a sap-sucking insect with a broad host range. Arabidopsis thaliana responds to GPA infestation with elevated expression of the PHYTOALEXIN DEFICIENT4 (PAD4) gene. Previously, we had demonstrated that the loss of PAD4 gene function compromises Arabidopsis resistance to GPA. In contrast, a mutation in the Arabidopsis SUPPRESSOR OF SALICYLIC ACID INSENSITIVITY2 (SSI2) gene, which encodes a desaturase involved in lipid metabolism, resulted in hyper-resistance to GPA. We demonstrate here that PAD4 is required for the ssi2-dependent heightened resistance to GPA. Based on electrical monitoring of insect behavior and bioassays in which the insect was given a choice between the wild type and the ssi2 mutant, it is concluded that the ssi2-conferred resistance is not due to deterrence of insect settling or feeding from the phloem of the mutant. Instead, hyper-resistance in the ssi2 mutant results from heightened antibiosis that curtails insect reproduction. Petiole exudates collected from uninfested ssi2 plants contain elevated levels of an activity that interferes with aphid reproduction in synthetic diets. PAD4 was required for the accumulation of this antibiotic activity in petiole exudates, supporting the role of PAD4 in phloem-based resistance. Because PAD4 expression is not elevated in the ssi2 mutant, we suggest that basal PAD4 expression contributes to this antibiosis.


Associations of cytosine deaminase gene polymorphisms with effectiveness of gemcitabine/cisplatin chemotherapy in patients of Xinjiang Uyghur and Han nationality with non-small cell lung cancer.
Cytidine deaminase (CDA) polymorphisms may affect the response to gemcitabine/cisplatin chemotherapy in patients with non-small cell lung cancer (NSCLC). This study is designed to investigate the associations of CDA-79A>C and 208G>A polymorphisms and gemcitabine/cisplatin chemotherapy effectiveness in Xinjiang Uyghur and Han patients. This prospective cohort study enrolled consecutive patients with stage IIIb/IV NSCLC administered gemcitabine/cisplatin chemotherapy at the First Affiliated Hospital, Medical College of Shihezi University and the First People's Hospital, Kashgar Region. CDA-A79C and CDA-G208A polymorphisms were detected by direct sequencing. Progression-free survival was analyzed by the Kaplan-Meier method. Associations of A79C and G208A polymorphisms with treatment effectiveness and progression-free survival were analyzed using logistic regression and multivariate Cox regression analyses. Subgroup analyses based on ethnicity were performed. The study enrolled 120 patients. A79C and G208A polymorphisms followed the Hardy-Weinberg equilibrium. The frequencies of the AA, AC, and CC genotypes and the A and C alleles of A79C were 52.2%, 29.9%, 17.9%, 67.2%, and 32.8%, respectively, in Han patients and 75.4%, 18.9%, 5.7%, 84.9%, and 5.1%, respectively, in Uyghur patients. Uyghur patients had lower frequencies of A79C-AC/CC genotypes, A79C-C allele, G208A-GA genotype, and G208A-A allele (P<0.05). Compared with A79C-AA, the odds of ineffective chemotherapy were increased for A79C-AC (odds ratio [OR] 2.818; 95% confidence interval [95% CI] 1.031, 7.705; P=0.043) and A79C-CC (OR 9.864; 95% CI 1.232, 78.966; P=0.031). G208A polymorphisms did not influence chemotherapy effectiveness. Chemotherapy was more effective in Han patients than in Uyghur patients for A79C-AC and G208A-GG. Progression-free survival was longer for A79C-AA versus A79C-AC/CC (10 vs. 7 months, P=0.004) and G208A-GA/AA vs. G208A-AA (12 vs. 8 months, P=0.010). Polymorphisms of A79C (hazard ratio [HR] 1.617; 95% CI 1.009, 2.592; P=0.046) and G208A (HR 2.193; 95% CI 1.055, 4.557; P=0.035) were associated with progression-free survival. For Uyghur and Han ethnic groups, A79C and G208A polymorphisms can be used as a promising biomarker for the chemotherapy efficacy and prognosis of NSCLC.


A 2D-3D structure transition of gold clusters on CeO2-X(111) surfaces and its influence on CO and O2 adsorption: a comprehensive DFT + U investigation.
Detailed knowledge of the structures of gold nanoparticles on ceria surfaces is of fundamental importance to understand their extraordinary activities in catalysis. In this work, we employ density functional theory with the inclusion of the on-site Coulomb interaction (DFT + U) to investigate the structure evolution of small-sized gold (Au, Au4, Au8 and Au12) clusters on four types of reduced CeO2-X(111) surfaces: SSV (single surface oxygen vacancy), LSVT (linear surface oxygen vacancy trimer), dLSVC (double linear surface oxygen vacancy with a surface vacancy dimer and a subsurface vacancy), and TSVT (triangular surface oxygen vacancy trimer). Our results indicate that the relative stabilities of multilayer (3D) structures are strengthened gradually compared with the monolayer (2D) structures with increasing the number of gold atoms. In addition, the 2D-3D structure transition occurs on the size order of Au(2D → 3D)@TSVT > Au(2D → 3D)@dLSVC ∼ Au(2D → 3D)@LSVT > Au(2D → 3D)@SSV, which is determined by the charge transfer magnitude between the CeO2 surfaces and gold clusters. Meanwhile, two competitive nucleation patterns are observed, fcc-like nucleation and hcp-like nucleation, which highly affect the morphology of supported gold clusters. Further site-by-site investigations indicate that the coordination number and the charges of Au atoms are the dominant factors to influence the adsorption strength of CO and O2, and the interface plays a relatively minor role. These findings not only enrich our knowledge of the relationship between surface defects, gold cluster structures and small molecule adsorptions, but also provide a theoretical perspective to help design the optimal Au/CeO2 systems possessing high catalytic efficiency.


Expression of p25 impairs contextual learning but not latent inhibition in mice.
The cyclin-dependent kinase 5 activator p25, which is derived from cleavage of p35, is thought to be formed in the brain of patients with Alzheimer's disease and schizophrenia. Female, but not male, transgenic mice expressing low levels of p25 have enhanced hippocampal long-term potentiation and improved spatial learning, raising the hypothesis that p25 may compensate for early learning deficits in Alzheimer's disease in a sex-dependent manner. Here, we show that low levels of p25 do not alter latent inhibition, a phenomenon that is impaired in patients with schizophrenia. We also demonstrate that contextual fear conditioning is impaired in female, but not in male, p25 transgenic mice. Thus, low levels of p25 are not always beneficial for learning as was previously hypothesized.


Crashing from cadaver to computer: Covid-driven crisis-mode pedagogy spawns active online substitute for teaching gross anatomy.
In early 2020, the Covid-19 crisis forced medical institutions worldwide to convert quickly to online platforms for content delivery. Although many components of medical education were adaptable to that format, anatomical dissection laboratory lost substantial content in that conversion, including features of active student participation, three-dimensional spatial relationships of structures, and the perception of texture, variation, and scale. The present study aimed to develop and assess online anatomy laboratory sessions that sought to preserve benefits of the dissection experience for first-year medical students. The online teaching package was based on a novel form of active videography that emulates eye movement patterns that occur during processes of visual identification, scene analysis, and learning. Using this video-image library of dissected materials, content was presented through asynchronous narrated laboratory demonstrations and synchronous/active video conference sessions and included a novel, video-based assessment tool. Data were obtained using summative assessments and a final course evaluation. Test scores for the online practical examination were significantly improved over those for previous in-person dissection-based examinations, as evidenced by several measures of performance (Mean: 2015-2019: 82.5%; 2020: 94.9%; P = 0.003). Concurrently, didactic test scores were slightly, but not significantly, improved (Mean: 2015-2019: 88.0%; 2020: 89.9%). Student evaluations of online sessions and overall course were highly positive. Results indicated that this innovative online teaching package can provide an effective alternative when in-person dissection laboratory is unavailable. Although this approach consumed considerable faculty time for video editing, further development will include video conference breakout rooms to emulate dissection small-group teamwork.


Achieving Lower Nitrogen Balance and Higher Nitrogen Recovery Efficiency Reduces Nitrous Oxide Emissions in North America's Maize Cropping Systems.
Few studies have assessed the common, yet unproven, hypothesis that an increase of plant nitrogen (N) uptake and/or recovery efficiency (NRE) will reduce nitrous oxide (N2O) emission during crop production. Understanding the relationships between N2O emissions and crop N uptake and use efficiency parameters can help inform crop N management recommendations for both efficiency and environmental goals. Analyses were conducted to determine which of several commonly used crop N uptake-derived parameters related most strongly to growing season N2O emissions under varying N management practices in North American maize systems. Nitrogen uptake-derived variables included total aboveground N uptake (TNU), grain N uptake (GNU), N recovery efficiency (NRE), net N balance (NNB) in relation to GNU [NNB(GNU)] and TNU [NNB(TNU)], and surplus N (SN). The relationship between N2O and N application rate was sigmoidal with relatively small emissions for N rates <130 kg ha-1, and a sharp increase for N rates from 130 to 220 kg ha-1; on average, N2O increased linearly by about 5 g N per kg of N applied for rates up to 220 kg ha-1. Fairly strong and significant negative relationships existed between N2O and NRE when management focused on N application rate (r2 = 0.52) or rate and timing combinations (r2 = 0.65). For every percentage point increase, N2O decreased by 13 g N ha-1 in response to N rates, and by 20 g N ha-1 for NRE changes in response to rate-by-timing treatments. However, more consistent positive relationships (R2 = 0.73-0.77) existed between N2O and NNB(TNU), NNB(GNU), and SN, regardless of rate and timing of N application; on average N2O emission increased by about 5, 7, and 8 g N, respectively, per kg increase of NNB(GNU), NNB(TNU), and SN. Neither N source nor placement influenced the relationship between N2O and NRE. Overall, our analysis indicated that a careful selection of appropriate N rate applied at the right time can both increase NRE and reduce N2O. However, N2O reduction benefits of optimum N rate-by-timing practices were achieved most consistently with management systems that reduced NNB through an increase of grain N removal or total plant N uptake relative to the total fertilizer N applied to maize. Future research assessing crop or N management effects on N2O should include N uptake parameter measurements to better understand N2O emission relationships to plant NRE and N uptake.


[Gastric histoplasmosis simulating a malignant gastric ulcer].
The case evaluated hereunder is that of a young patient, from a Histoplasmosis-endemic area, reporting chronic abdominal pain. An upper gastric endoscopy evidenced the presence of gastric compromise, characterized by evident infiltrating ulcerous damage simulating a carcinoma. The final diagnosis was chronic disseminated histoplasmosis with gastric compromise. The patient presented as an underlying condition, a chronic alcoholic hepatopathy. Histoplasmosis must be included in the differential diagnosis of ulcerated and/or infiltrated lesions of the gastrointestinal tract in patients from endemic areas or susceptible to immunosuppression conditions.


Improving care and efficiency: appointment times in a haemodialysis unit.
Shortage of nurses and dialysis spaces and the desire to improve patient care are the two main driving forces in the dialysis field today. This paper suggests that these issues can be addressed by organisational change. We describe a simple, dramatically effective but rarely used example - the effect on a haemodialysis unit of the introduction of patient appointment times. This paper will demonstrate that appointment times can be highly effective in reducing waiting times for patients and in utilizing staff and resources more efficiently, as long as there is commitment from key staff to implement and maintain them effectively


Resting metabolic rates of obese women after rapid weight loss.
Reduced energy expenditure associated with reduced energy intake has been used as an explanation for resistance to weight loss in obese patients. Decreases in serum T3 concentrations and body cell mass induced by restriction of energy intake may contribute to the reduced energy needs. In the present study, mean resting metabolic rate (RMR) was reduced by 9.4% after 5 weeks of a very low energy diet (472 Cal/day) in six obese women, and the mean serum T3 concentration decreased 46%. However, the lowest RMR values measured were similar in these subjects (mean, 1328 Cal/day; range, 1110-1578 Cal/day) to RMR values of lean women (n = 19; mean, 1241 Cal/day; range, 938-1450 Cal/day) and moderately overweight women ingesting ad libitum diets (n = 8; mean, 1335 Cal/day; range, 1064-1533). Decreases in total body potassium (10%) and 24-h urinary creatinine excretion (23%) suggested that there was a substantial loss of body cell mass during weight loss, whereas nitrogen balance suggested that changes in body cell mass were slight. These data and those of previous studies indicate that even after rapid weight loss, the resting energy requirements of obese or previously obese subjects are not abnormally low relative to those of nonobese subjects, even though the concentrations of T3, a major thermogenic hormone, are substantially reduced. The hypometabolic response to weight loss cannot explain the failure of obese subjects to lose weight on weight-reducing regimens.


Benzophenone 1 induced photogenotoxicity and apoptosis via release of cytochrome c and Smac/DIABLO at environmental UV radiation.
Solar UV radiation is main factor of photocarcinogenesis, photoageing, and phototoxicity; thus, protection from UV radiation is major concern. Sunscreens containing UV filters are suggested as sun safe practices, but safety of UV filters remains in controversies. Benzophenone-1 (BP1) is commonly used in sunscreens as UV blocker. We assessed the photogenotoxicity and apoptotic parameters in human keratinocytes (HaCaT cells) by western blot, immunocytochemistry, flowcytometry, comet assay and TEM imaging. Our results exposed that BP1 photosensitized and generated intracellular ROS (2.02 folds) under sunlight/UVR. Decrease in cell viability was recorded as 80.06%, 60.98% and 56.24% under sunlight, UVA and UVB, respectively. Genotoxic potential of BP1 was confirmed through photomicronuclei and CPDs formation. BP1 enhanced lipid peroxidation and leakage of LDH enzyme (61.7%). Apoptotic cells were detected by AnnexinV/PI staining and sub G1 population of cell cycle. BP1 induced up regulation of apoptotic proteins Bax/Bcl2 ratio, Apaf-1, cytochrome c, Smac/DIABLO and cleaved caspase 3 was noticed. Down regulation of pro caspase 3 was inhibited by Z-VAD-fmk (inhibitor of caspase). Thus, study established the involvement of BP1 in photogenotoxicity and apoptosis via release of cytochrome c and Smac/DIABLO. These findings suggest sunscreen user to avoid BP1 in cosmetics preparation for its topical application.


Transport and metabolism of the essential vitamin pantothenic acid in human erythrocytes infected with the malaria parasite Plasmodium falciparum.
The growth of the human malaria parasite, Plasmodium falciparum, within its host erythrocyte is reliant on the uptake of a number of essential nutrients from the extracellular medium. One of these is pantothenic acid, a water-soluble vitamin that is a precursor of coenzyme A. In this study we show that normal uninfected erythrocytes are impermeable to pantothenate but that the vitamin is taken up rapidly into malaria-infected cells via a transport pathway that has the characteristics (furosemide sensitivity, nonsaturability) of previously characterized, broad specificity permeation pathways induced by the intracellular parasite in the host cell membrane. The transport of pantothenate therefore constitutes a critical physiological role for these pathways. Inside the parasitized cell pantothenate undergoes phosphorylation, the first step in its conversion to coenzyme A. Parasites within saponin-permeabilized erythrocytes were shown to take up and phosphorylate pantothenate, consistent with the intracellular parasite having both a pantothenate transporter and a pantothenate kinase. Comparisons of the rate of phosphorylation of pantothenate by lysates prepared from uninfected and infected erythrocytes revealed that the pantothenate kinase activity of the P. falciparum trophozoite is some 10-fold higher than that of its host cell and that most, if not all, of the phosphorylation of pantothenate within the malaria-infected cell occurs within the intracellular parasite. These results contrast with those of previous studies in which it was proposed that the avian malaria parasite Plasmodium lophurae lacks pantothenate kinase (as well as the other enzymes for the synthesis of coenzyme A) and is reliant upon the uptake of preformed coenzyme A from the host cell cytosol.


Chemical composition of clarified bayberry (Myrica rubra Sieb. et Zucc.) juice sediment.
Clarified bayberry juice turned hazy upon storage at 25 degrees C for 6 months, and the chemical composition of centrifugally separated sediment was analyzed. Bayberry juice haze was mainly protein-tannin haze. The lyophilized sediment contained 20.4 +/- 4.3% of protein, 70.2 +/- 2.6% of total polyphenols, 7.2% of monosaccharides, and 6.7 +/- 0.6% of ash. Amino acid analyses and molecular weight distribution estimation indicated that bayberry proteins were haze-active proteins with a molecular weight less than 8 kDa. Gallic acid, quercetin hexoside, quercetin deoxyhexoside, and quercetin were found in the methanol-dissolved sample, while gallic acid, protocatechuic acid, cyanidin, ellagic acid, and quercetin were detected in the acid-hydrolyzed sample. Ellagic acid was the dominant individual phenolic (9.9 +/- 0.19 g/100 g dry weight, 55.3% of the total amount) in the sediment. Monosaccharides of rhamnose, arabinose, mannose, glucose, and galactose in the sediment were most probably the glycoside moieties of the anthocyanins, flavonols, and elllagitannins. Metal ions of calcium, magnesium, potassium, iron, and copper also indicated the heterogeneous characteristics of the sediment.


Severe vitamin D deficiency is associated with endothelial inflammation in healthy individuals even in the absence of subclinical atherosclerosis.
Vitamin D has beneficial effects, some of which involve the cardiovascular system. No study to date has investigated the association between serum endocan levels, as a biomarker of endothelial inflammation, and vitamin D levels in the absence of subclinical atherosclerosis detected by carotid intima-media thickness (CIMT) in healthy individuals. Subjects were categorized into three groups based on vitamin D levels according to Endocrine Society guidelines. Mean CIMT was calculated from six measurements on two scans. Statistical significance was set at p < 0.05, and all testing was two-sided. The concentration of serum endocan was 802.8 ± 411.4 ng/L in the group with the lowest serum vitamin D level, 454.8 ± 334.3 ng/L in the mild/moderately low serum vitamin D level group, and 269.4 ± 180.2 ng/L in the group with normal serum vitamin D levels (p < 0.01). Receiver operating characteristics curve analysis revealed that a serum vitamin D concentration of 7.5 ng/mL had a 97% sensitivity and 81% specificity for the prediction of serum endocan level greater than 270 ng/L, which could be an indicator for endothelial inflammation. Demonstrating that vitamin D deficiency can cause endothelial damage in the early period of atherosclerosis without the development of clinical cardiovascular disease will have a pivotal role in the prevention of cardiovascular mortality and morbidity.


Technique for blepharoptosis correction using double-breasted orbicularis oculi muscle flaps.
The technique that uses the orbicularis oculi muscle flap to elevate the upper eyelid has become a popular surgical alternative for blepharoptosis. This method is especially effective in cases of severe blepharoptosis with poor levator muscle function. In this technique, the superiorly based orbicularis oculi muscle flap (which is connected to the frontalis muscle anatomically) is advanced and attached to the tarsal plate, thus enabling dynamic elevation of the upper eyelid. However, a temporary period of lagophthalmos occurs with the original method. Although the problem is temporary, it typically lasts 2 to 6 months and may lead to serious eye emergencies. We describe a modification that eliminates lagophthalmos, which is the main drawback of the original technique. Two orbicularis oculi muscle flaps are created, one superiorly based and one inferiorly based. The inferiorly based flap corresponds to the strip of pretarsal orbicularis oculi that is considered "excess" and is discarded in other methods. Our aim with this modified technique is to preserve as much of the pretarsal part of the orbicularis oculi muscle as possible, and thus enable immediate tight eyelid closure postoperatively and achieve dynamic, powerful eyelid-opening action. We have used this technique in 7 patients (11 eyelids total) during the past 5 years and have achieved favorable results. All 11 operated eyelids showed immediate tight closure postoperatively, as well as dynamic, powerful eyelid-opening action. This operation is a good alternative for patients with severe ptosis who have insufficient levator function and for cases that have recurred after operations with other methods. Local native tissues are used and dynamic correction is achieved with a single incision. The need for intensive eye care is eliminated and there is less risk of corneal damage in the early postoperative period. Above all, this technique yields predictable eyelid-opening action.


Team Approach to Improving Radiologist Wellness: A Case-Based Methodology.
Radiologist wellness is important on an individual and group/institutional level and helps to promote a strong and healthy working environment, which can improve radiologist retention and engagement. This paper will discuss case examples of radiologist wellness improvements in a single academic institution over a 3-year period using the DMAIC (Define, Measure, Analyze, Improve, and Control) model. Leveraging this framework led to the implementation of reading room assistants, reduction in work-related injuries by improvements in ergonomics, and the formation of a faculty mentorship program.


Identification of double-stranded genomic DNA spanning all chromosomes with mutated KRAS and p53 DNA in the serum exosomes of patients with pancreatic cancer.
Exosomes are small vesicles (50-150 nm) of endocytic origin that are released by many different cell types. Exosomes in the tumor microenvironment may play a key role in facilitating cell-cell communication. Exosomes are reported to predominantly contain RNA and proteins. In this study, we investigated whether exosomes from pancreatic cancer cells and serum from patients with pancreatic ductal adenocarcinoma contain genomic DNA. Our results provide evidence that exosomes contain >10-kb fragments of double-stranded genomic DNA. Mutations in KRAS and p53 can be detected using genomic DNA from exosomes derived from pancreatic cancer cell lines and serum from patients with pancreatic cancer. In addition, using whole genome sequencing, we demonstrate that serum exosomes from patients with pancreatic cancer contain genomic DNA spanning all chromosomes. These results indicate that serum-derived exosomes can be used to determine genomic DNA mutations for cancer prediction, treatment, and therapy resistance.


drVM: a new tool for efficient genome assembly of known eukaryotic viruses from metagenomes.
Virus discovery using high-throughput next-generation sequencing has become more commonplace. However, although analysis of deep next-generation sequencing data allows us to identity potential pathogens, the entire analytical procedure requires competency in the bioinformatics domain, which includes implementing proper software packages and preparing prerequisite databases. Simple and user-friendly bioinformatics pipelines are urgently required to obtain complete viral genome sequences from metagenomic data. This manuscript presents a pipeline, drVM (detect and reconstruct known viral genomes from metagenomes), for rapid viral read identification, genus-level read partition, read normalization, de novo assembly, sequence annotation, and coverage profiling. The first two procedures and sequence annotation rely on known viral genomes as a reference database. drVM was validated via the analysis of over 300 sequencing runs generated by Illumina and Ion Torrent platforms to provide complete viral genome assemblies for a variety of virus types including DNA viruses, RNA viruses, and retroviruses. drVM is available for free download at: https://sourceforge.net/projects/sb2nhri/files/drVM/ and is also assembled as a Docker container, an Amazon machine image, and a virtual machine to facilitate seamless deployment. drVM was compared with other viral detection tools to demonstrate its merits in terms of viral genome completeness and reduced computation time. This substantiates the platform's potential to produce prompt and accurate viral genome sequences from clinical samples.


Protective effects of beta-glucan extracted from barley against benzo[a]pyrene-induced DNA damage in hepatic cell HepG2.
The aim of the present study was to assess the genotoxic and antigenotoxic effect of beta-glucan (BG) extracted from barley. The genotoxicity of BG was tested in the single-cell gel electrophoresis assays (SCGE)/HepG2 test system. Moreover, the protective effects of BG against the genotoxicity of B[a]P were studied to delineate its mechanism of antigenotoxicity using four different treatment protocols - pre-treatment, simultaneous simple, simultaneous with pre-incubation, and post-treatment. The results showed that the compound itself was devoid of mutagenic activity at the three lower concentrations studied (1, 5, and 25microg/mL); however, genotoxic and cytotoxic effects were seen at 100 and 200microg/mL, respectively. In combination experiments with B[a]P, pronounced inhibition of DNA migration in the SCGE assay was observed in the two simultaneous treatments, and a smaller reduction was observed in the two other treatments. Thus, the data suggest that BG acts through binding to the genotoxic compound or capturing free radicals produced during its activation. However, the protective effects observed with pre-treatment and post-treatment suggest that the BG may be modulating cell metabolism.


Cardiogenic shock elicits acute inflammation, delayed eosinophilia, and depletion of immune cells in most severe cases.
Patients with cardiogenic shock (CS) display systemic inflammation and a high rate of infections, suggesting important immune disturbances. To explore the immune response to CS, we prospectively measured, in 24 consecutive CS patients, differential white blood cell (WBC) counts and the cytokines IL-1β, IL-5, IL-6, IL-10, TNFα, IFNγ, MCP-1 and eotaxin (CCL11), at Day 1 (T1), day 3 (T2) and day 6-8 (T3). Secondary infections and their influence on cytokines and WBCs were determined. CS induced early (T1) neutrophilia and elevated levels of IL-6, IL-10 and MCP-1, correlating with shock severity. The eosinophil chemoattractant eotaxin was elevated at T1 and decreased thereafter, and a progressive rise of blood eosinophils was noted over time. Patients with the most severe shock had reduced lymphocytes and monocytes at T2 and T3. Sixty-two percent of patients developed an infection, which did not alter the profile of immune response, except from higher IL-6 levels at T2. Therefore, CS elicits an acute pro-inflammatory response, followed by a delayed increase in blood eosinophils, consistent with the development of a tissue repair response, as well as depletion of immune cells in the most severely affected patients, which might predispose to secondary infections.


Correlating changes in body temperature with infectious outcome in febrile children who receive acetaminophen.
We reviewed the body-temperature patterns of 140 children ages 2 to 24 months who had fever > or = 39.0 degrees C, received acetaminophen 10 to 15 mg/kg, and had their temperatures remeasured 60 to 90 min later. The children comprised three groups: 22 had bacterial meningitis; 59, isolated bacteremia; and 59, nonbacterial febrile illness. Percentages of patients who became afebrile (temperature < 38.0 degrees C) after receiving acetaminophen were not significantly different among the three groups. Differences in mean temperature decrease after antipyretic was given were significant within each group but not between groups. An inverse relation (P < .004) between patient age and magnitude of temperature was revealed by the following formula: degrees C of defervescence = 1.66 - (0.028 x patient age in months). Thus, highly febrile young children with and without invasive bacterial infections who receive a therapeutic dose of acetaminophen experience a significant temperature drop after 60 to 90 min but do not commonly defervesce to an afebrile state. The degree of defervescence is age-dependent and does not distinguish between infectious outcomes.


Update on the Treatment of Scars
Background: Treatment of scars continues to be a persisting challenge. Scar classification is paramount in determining an appropriate treatment strategy. They can be classified into hypertrophic, keloid, or atrophic scars. With the increasing demand for less invasive procedures that result in equal or greater outcomes, there has been an increase in the variety of procedures for the management of scarring. Methods: A Pubmed search was performed for the most recent papers on scar treatments. Findings and applications are discussed in this review. Results: Studies evaluating the efficacy and safety of microneedling, filler agents, toxins, silicone gels, and laser devices such as ablative, non-ablative, fractional, SRT, and radiofrequency are discussed. Conclusion: Review of the literature revealed a myriad of options for the treatment of different scar types. Although there is not vast evidence in the literature in regard to combination treatments, these are becoming more popular, and it is the author's opinion that combination treatments yield better overall results. J Drugs Dermatol. 2019;18(6):550-555.


[Rare indications for an external fixator].
Seldom indications for the use of external fixator are reported and illustrated. As a rule the damage to the pelvis is complex and it is often associated with a polytrauma; unstable pelvis injuries in some cases can be stabilised by external fixator by the method of Slätis. Examples of osteotaxis are given for the treatment of comminuted fractures or defect-pseudarthroses or after osteomyelitic bone damage of femur and humerus. In the treatment of multi-fragment fractures of the base of the radius and of the forearm the external fixation can also be used with good success. The external mini-fixator is a new way for external stabilization in hand surgery and can provide good results in comminuted fractures of the fingers and for finger-replantation.


Calculating binding free energies of host-guest systems using the AMOEBA polarizable force field.
Molecular recognition is of paramount interest in many applications. Here we investigate a series of host-guest systems previously used in the SAMPL4 blind challenge by using molecular simulations and the AMOEBA polarizable force field. The free energy results computed by Bennett's acceptance ratio (BAR) method using the AMOEBA polarizable force field ranked favorably among the entries submitted to the SAMPL4 host-guest competition [Muddana, et al., J. Comput.-Aided Mol. Des., 2014, 28, 305-317]. In this work we conduct an in-depth analysis of the AMOEBA force field host-guest binding thermodynamics by using both BAR and the orthogonal space random walk (OSRW) methods. The binding entropy-enthalpy contributions are analyzed for each host-guest system. For systems of inordinate binding entropy-enthalpy values, we further examine the hydrogen bonding patterns and configurational entropy contribution. The binding mechanism of this series of host-guest systems varies from ligand to ligand, driven by enthalpy and/or entropy changes. Convergence of BAR and OSRW binding free energy methods is discussed. Ultimately, this work illustrates the value of molecular modelling and advanced force fields for the exploration and interpretation of binding thermodynamics.


Facile synthesis of boron nitride nanotubes and improved electrical conductivity.
A layer of catalyst film on substrate is usually required during the vapor-liquid-solid (VLS) growth of one-dimensional (1D) nanomaterials. In this work, however, a novel approach for synthesizing high-purity bamboo-like boron nitride (BN) nanotubes directly on commercial stainless steel foils was demonstrated. Synthesis was realized by heating boron and zinc oxide (ZnO) powders at 1200 degrees C under a mixture gas flow of nitrogen and hydrogen. The stainless steel foils played an additional role of catalyst besides the substrate during the VLS growth of the nanotubes. In addition, the electrical conductivity of the BN nanotubes was efficiently improved in a simple way by coating with Au and Pd nanoparticles. The decorated BN nanotubes may find potential applications in catalysts, sensors and nanoelectronics.


Emerging technology: A key enabler for modernizing pharmaceutical manufacturing and advancing product quality.
Issues in product quality have produced recalls and caused drug shortages in United States (U.S.) in the past few years. These quality issues were often due to outdated manufacturing technologies and equipment as well as lack of an effective quality management system. To ensure consistent supply of safe, effective and high-quality drug products available to the patients, the U.S. Food and Drug Administration (FDA) supports modernizing pharmaceutical manufacturing for improvements in product quality. Specifically, five new initiatives are proposed here to achieve this goal. They include: (i) advancing regulatory science for pharmaceutical manufacturing; (ii) establishing a public-private institute for pharmaceutical manufacturing innovation; (iii) creating incentives for investment in the technological upgrade of manufacturing processes and facilities; (iv) leveraging external expertise for regulatory quality assessment of emerging technologies; and (v) promoting the international harmonization of approaches for expediting the global adoption of emerging technologies.


Prednisolone bioavailability in the dog.
With a fasted dog as an animal model, the bioavailability and pharmacokinetics of prednisolone were studied following rapid intravenous injection and oral dosing of a prednisolone sodium phosphate solution and also following oral doses of prednisolone as tablets and a slurry. Hydrolysis of the phosphate ester to prednisolone in the body is extremely rapid and complete, thus permitting accurate calculation of the distribution volume of prednisolone. Enteral absorption of prednisolone from a slurry is superior to that from prednisolone tablets and from a prednisolone sodium phosphate solution. Reduced absorption from tablets, compared to the slurry, is probably due to tablet disintegration characteristics; reduced absorption from the solution is probably due to poor membrane permeability of the ionized drug. Information obtained from a single animal may indicate the need for expanded studies in humans.


Characterization of a Novel Chitinase from Sweet Potato and Its Fungicidal Effect against Ceratocystis fimbriata.
Black rot, caused by Ceratocystis fimbriata, is a destructive disease of sweet potatoes (Ipomoea batatas). In this study, a novel chitinase (IbChiA) was screened from sweet potatoes, which showed a remarkably higher expression level in resistant varieties than in susceptible ones after inoculation with C. fimbriata. Sequence analysis indicated that IbChiA belongs to family 19 class II extracellular chitinase with a MW of 26.3 kDa and pI of 5.96. Recombinant IbChiA, produced by Pichia pastoris, displayed antifungal activity and stability. IbChiA could restrain the mycelium extension of C. fimbriata. FDA/PI double staining combined with transmission electron microscopy observation revealed the remarkable fungicidal effect of IbChiA on the conidia of C. fimbriata. The disease symptoms on the surface of slices and tuberous roots of sweet potatoes were significantly reduced after treatment with IbChiA. These results indicated that IbChiA could be used as a potential biofungicide to replace chemical fungicides.


The association between oral disease and type of antiretroviral therapy among perinatally HIV-infected youth.
This study explores the association between combination antiretroviral therapy (cART) and oral health outcomes (dental and periodontal) among perinatally HIV-infected (PHIV) youth. We conducted a cross-sectional study of oral health among PHIV youth participating in the Oral Health substudy of the Pediatric HIV/AIDS Cohort Study (PHACS). Dentists at research sites were trained/calibrated on how to perform a standardized oral mucosal, dental and periodontal examination. They assessed the decayed-missing-filled-surfaces and teeth index (DMFS/T). The number of decayed surfaces and teeth and the number of teeth with gingival bleeding on probing for each participant were derived from the examination. Data for analysis included lifetime measurements of CD4 cell count and viral load, sociodemographic information and current/past history of ART. Among 209 PHIV youth, 95% were on ART at the time of enrolment. Among 143 PHIV youth on the same cART for at least 1 year, we found that the mean decayed teeth score of those receiving cART containing an integrase inhibitor was 86% higher than that of those on cART without an integrase inhibitor after adjusting for age, lifetime proportion of unsuppressed viral load and CD4 cell count nadir. Initiating protease inhibitors before age 6 years was associated with a significantly lower DMFT score than participants who initiated at age 6 years and older. Our study revealed that PHIV youth who received cART containing an integrase inhibitor had a significantly higher number of untreated active caries than those on cART without an integrase inhibitor. This may warrant closer dental surveillance of those receiving an integrase inhibitor.


Pregnancy and pregnancy outcome among women with inflammatory skin diseases.
The effect of inflammatory skin diseases on pregnancy has been incompletely characterized. We sought to estimate the incidence of pregnancy and pregnancy outcomes among women with inflammatory skin diseases. Cohort study of women with atopic dermatitis (AD), psoriasis, other inflammatory skin diseases, and comparison group, followed for pregnancies and pregnancy outcomes. There were 3,131 pregnancies among 64,773 woman-years (4.8/100) in women with skin diseases, and 2,592 pregnancies among 59,826 woman-years (4.3/100) in the comparison group. The age-standardized incidence of pregnancy was similar to the comparison group [rate ratio (RR) = 1.2, 95% confidence interval (CI) 1.0-1.4 for AD, RR = 1.1, 95% CI 1.0-1.2 for psoriasis, and RR = 1.1, 95% CI 1.0-1.1 for other]. Spontaneous abortion was also similar to the comparison group (RR = 1.2 for AD, 95% CI 1.0-1.4, RR = 1.1, 95% CI 1.0-1.2 for psoriasis, and RR = 1.1, 95% CI 1.0-1.1 for other). Our results suggest little effect of skin disease on incidence or outcome of pregnancy.


Chondromyxoid fibroma of the sacrum: A case report and literature review.
Chondromyxoid fibroma (CMF) is an extremely rare, benign cartilaginous tumor that makes up <0.5% of all bone tumors, typically presenting in the second or third decade of life. CMF of the sacrum is exceedingly rare, with only seven documented cases reported in the neurosurgical literature. We report a case of a 35-year-old female with a 3 month history of lower back pain after sustaining a fall on her sacrum/coccyx presenting with a progressive complaint of localized lower back pain, occasional urinary retention without incontinence, gluteal hypesthesia, and pressure below the gluteal crease. Imaging demonstrated a large, expansile enhancing soft-tissue lesion involving the sacrum, distal to the S2-3 disc space. The tumor was removed with partial sacrectomy for open en bloc resection with partial nerve sparing. The patient was found at 1.5-year follow-up with the improvement of symptoms, no recurrence, and no residual neurologic dysfunction. Sacral CMF is a rare clinical entity that may mirror more aggressive sacral pathology, including chordoma, in both clinical presentation and imaging characteristics. A review of the available literature regarding diagnosis, surgical management options, and prognosis for sacral CMF is provided.


Indigenous Austalians and physical activity: using a social-ecological model to review the literature.
This paper aims to present what is currently known about Indigenous Australians and their engagement in physical activity and to then challenge some of the 'taken-for-granted' ways of thinking about promoting or researching physical activity with Indigenous Australians. Major health, education and sport databases, as well as government websites were searched using the key terms of physical activity, sport, leisure, recreation, Indigenous and Aboriginal/Aborigine. A social-ecological model of health was adapted and used as an organizing framework to synthesize the literature. It is concluded that socioecological models can be valuable tools for understanding and promoting issues related to physical activity engagement for a range of populations but they may require complementary critical insights, including those from Indigenous perspectives. Productive theoretical spaces where Western and Indigenous knowledges come together can assist health educators to consider the complexity and diversity of Indigenous people's lived experiences when planning and implementing programs.


Complementary and alternative medicine--a consumer CAM-paign.
Complementary and alternative medicine (CAM) isn't just for the "New Age" set anymore-increasingly, patients are voting with their feet, choosing those institutions that offer CAM therapies.


Bet v 1- and Bet v 2-Associated Plant Food Sensitization in Uganda and Germany: Differences and Similarities.
Birch pollen allergy and concomitant plant food sensitization are well documented in Europe. However, there are currently no data available on pollen-associated plant food sensitization or even pollen allergy in tropical Africa. Our study aimed to investigate Bet v 1- and Bet v 2-associated plant food sensitization in atopic patients from Uganda and compare it with sensitization rates in German patients. Sera from 83 Ugandan and 97 German atopic patients were analysed using UniCAP100™ for allergen-specific IgE against the birch tree pollen allergens Bet v 1 and Bet v 2 as well as the plant foods hazelnut, apple, kiwi, pea, peach, cherry, litchi, peanut, and soy. As expected, sensitization to Bet v 1 and cross-reactive plant food allergens was more common in German atopic patients. In contrast, the prevalence of sensitization against Bet v 2 was remarkably similar in Ugandan and German patients. Interestingly, in Ugandan patients we found IgE-mediated sensitization against plant foods such as hazelnut, pea, peach, cherry, and litchi that are neither cultivated nor consumed in Uganda. For Ugandan atopic patients, sensitization against the Bet v 2 allergen (a plant profilin) may explain cross-reactivity to several plant foods which are not consumed in Uganda. Additionally, it is probable that sensitization of Ugandan atopics to alder pollen (Alnus acuminata, plant family Betulaceae) caused serological cross-reactivity with Betula verrucosa-related allergens.


Biaxial strain effect on the electronic structure and valleytronic properties of a MoS2/CoO(111) heterostructure.
The biaxial strain effect on the electronic structure and valleytronic properties, such as valley splitting and Berry curvature, of monolayer MoS2 induced by the magnetic proximity effect of an antiferromagnetic CoO(111) substrate is investigated by density functional theory. The biaxial tensile strain could continually tune the magnitude of spin and valley splitting of the MoS2/CoO(111) heterostructure, because the spin splitting at the K and K' valleys decreases, whereas the valley splitting increases slightly in the tensile strain range of 0-6%. The ferromagnetic order of MoS2 in the heterostructure induced by the magnetic CoO substrate is retained under a biaxial tensile strain of 2% to 6% compared with the unstrained case. In particular, the intensity of the exchange field due to the magnetic proximity effect of CoO weakens monotonously with biaxial tensile strain increasing from 0% to 6%, thereby also leading to a monotonous reduction of the Berry curvature. The regulation of valley splitting and Berry curvature by biaxial tensile strain will provide the MoS2/CoO(111) heterostructure with high potential in future valleytronic applications.


Interleukin-31 Polymorphisms and Serum IL-31 Level in Patients with Mastocytosis: Correlation with Clinical Presen-tation and Pruritus.
Data on interleukin-31 (IL-31) involvement in the patho-genesis of mastocytosis, and its impact on pruritus development in the disease, are limited. The aim of this study was to analyse distinct IL-31 gene polymorphisms in 127 patients (age 0.5-76 years) with mastocytosis and their correlation with clinical presentation, pruritus and serum IL-31 levels. In patients with mastocytosis, the frequency of IL-31 IVS2+12AA genotype and IVS2+12A allele was higher than in control subjects and they were linked to an increased risk of development of mastocytosis. In adult patients, but not in children, -2057AA genotype was also associated with an increased risk of occurrence of mastocytosis. Pruritus affected 83.3% of 78 adult patients with mastocytosis, and a positive correlation between serum IL-31 levels and pruritus was found in these patients. In conclusion, distinct polymorphic variants of the IL-31 gene may be involved in the patho-genesis of mastocytosis, and IL-31 may be involved in the induction of pruritus in patients with mastocytosis.


Genetic analysis of the G1 period: isolation of mutants (or variants) with a G1 perior from a Chinese hamster cell line lacking G1.
Cells of the Chinese hamster line V79-8 multiply without a G1 period (i.e., they are G1(-)) and have an average generation time of 9.5 hr. After mutagenesis and selection we have derived five stable mutants (or variants) of this line that have longer generation times. In each case the increase in generation time is due solely to the introduction of a G1 period into the cell cycle, with no measurable effect on S, G2, or M. Fusions among these five G1(+) mutant lines and another presumably nonmutant G1(+) line (V79-743) produce hybrid cells lacking a G1 period in all but one case. These complementation tests define five complementation groups among these six G1(+) cell lines. The six G1(+) lines represent five different causes or bases for the presence of a G1 period. The two G1(+) mutants belonging to complementation group V are temperature sensitive for expression of the G1(+) phenotype (G1 congruent with 0, 4, and 6 hr at 33 degrees , 37 degrees , and 39 degrees , respectively). In all cases the G1(-) state is dominant over the G1(+) state, suggesting that the presence of G1 represents a "deficient" condition. Mutants of this type may be useful in the analysis of the switch from G1(-) to G1(+) that occurs normally in cleaving embryos and in elucidation of the genetic mechanism(s) responsible for the presence of a measurable G1 in most cells.


Treatment of the acquired immune deficiency syndrome-related Kaposi's sarcoma with bleomycin as a single agent.
A nonrandomized trial was conducted to assess the efficiency and toxicity of bleomycin as a single agent in treatment of non-life-threatening AIDS-related Kaposi's sarcoma (KS). Sixty patients were enrolled in this study. They all had a disseminated and progressive non-life-threatening AIDS-related KS associated with systemic symptoms and/or CD4 lymphocyte count less than 400/mm3. Thirty patients were treated with intramuscular bleomycin (5 mg/d for 3 days every 2 or 3 weeks) and 30 others with a slow continuous intravenous infusion of bleomycin (6 mg/m3/d for 4 days every 4 weeks). The mean duration of therapy was 5 months (range, 2 to 24 months). A partial response was observed in 29 patients (48.3%) and the disease was stabilized in 18 additional patients (30%). Bleomycin failed in 21.6% of patients. Therapy had to be discontinued in two patients because of side effects. Thus bleomycin as a single agent is a good alternative therapy for AIDS-related KS.


Effects of Buprenorphine and Carprofen on Appetite in New Zealand White Rabbits (Oryctolagus cuniculus).
Rabbits are especially susceptible to adverse effects related to surgery, which can lead to inappetence and gastrointestinal (GI) stasis. However, these adverse effects may be related to discomfort from the procedure, anesthesia, the analgesics used, and the stress of restraint for analgesic administration. Opioid and NSAID analgesics which are frequently used in rabbits, can contribute to these adverse effects. This study compared the clinical GI side effects of buprenorphine and carprofen to saline controls in New Zealand White rabbits after a nonsurgical anesthetic event. Nine rabbits (3 females and 6 males, aged 8 to 20 mo) were randomly rotated through 5 treatment groups with a 7-d washout period between treatments: anesthesia control (no treatment), buprenorphine (0.05 mg/kg SC every 12 h for 72 h), carprofen (5 mg/kg SC every 24 h for 72 h), twice daily saline control (equivalent volume to buprenorphine SC every 12 h for 72 h), and once daily saline control (equivalent volume to carprofen SC every 24 h for 72 h). All rabbits were anesthetized 5 times and received initial treatments on the day of anesthesia. Generalized linear mixed models were used to assess food intake, water intake, and fecal output score for 7 days after anesthesia. Analysis showed that buprenorphine-treated rabbits had a significant 4-d decrease in food intake and a 3-d decrease in fecal output score compared with baseline. None of the other treatment groups showed any changes in food intake or fecal output score compared with baseline. These findings demonstrate that in the absence of pain, buprenorphine significantly depresses food intake in rabbits and that restraint and injections have minimal effect on food intake despite the possibility of increased stress.


An unexpected role for the yeast nucleotide exchange factor Sil1 as a reductant acting on the molecular chaperone BiP.
Unfavorable redox conditions in the endoplasmic reticulum (ER) can decrease the capacity for protein secretion, altering vital cell functions. While systems to manage reductive stress are well-established, how cells cope with an overly oxidizing ER remains largely undefined. In previous work (Wang et al., 2014), we demonstrated that the chaperone BiP is a sensor of overly oxidizing ER conditions. We showed that modification of a conserved BiP cysteine during stress beneficially alters BiP chaperone activity to cope with suboptimal folding conditions. How this cysteine is reduced to reestablish 'normal' BiP activity post-oxidative stress has remained unknown. Here we demonstrate that BiP's nucleotide exchange factor - Sil1 - can reverse BiP cysteine oxidation. This previously unexpected reductant capacity for yeast Sil1 has potential implications for the human ataxia Marinesco-Sjögren syndrome, where it is interesting to speculate that a disruption in ER redox-signaling (due to genetic defects in SIL1) may influence disease pathology.


Lupus and recurrent pregnancy loss: the role of female sex hormones and B cells.
Systemic lupus erythematosus is a debilitating autoimmune disease characterized by uncontrolled activation of adaptive immunity, particularly B cells, which predominantly affects women in a 9 to 1 ratio compared to men. This stark sex disparity strongly suggests a role for female sex hormones in the disease's onset and progression. Indeed, it is widely recognized that estradiol not only enhances the survival of autoreactive B cells but also stimulates the production of autoantibodies associated with systemic lupus erythematosus, such as anti-nuclear antibodies and anti-dsDNA antibodies. Clinical manifestations of systemic lupus erythematosus typically emerge after puberty and persist throughout reproductive life. Furthermore, symptoms often exacerbate during the premenstrual period and pregnancy, as increased levels of estradiol can contribute to disease flares. Despite being fertile, women with lupus face a heightened risk of pregnancy-related complications, including pregnancy loss and stillbirth, which significantly surpass the rates observed in the healthy population. Therefore, this review aims to summarize and discuss the existing literature on the influence of female sex hormones on B-cell activation in patients with systemic lupus erythematosus, with a particular emphasis on their impact on pregnancy loss.


Effects of auricular chondrocyte expansion on neocartilage formation in photocrosslinked hyaluronic acid networks.
The overall objective of this study was to examine the effects of in vitro expansion on neocartilage formation by auricular chondrocytes photoencapsulated in a hyaluronic acid (HA) hydrogel as a next step toward the clinical application of tissue engineering therapies for treatment of damaged cartilage. Swine auricular chondrocytes were encapsulated either directly after isolation (p = 0), or after further in vitro expansion ( p = 1 and p = 2) in a 2 wt%, 50-kDa HA hydrogel and implanted subcutaneously in the dorsum of nude mice. After 12 weeks, constructs were explanted for mechanical testing and biochemical and immunohistochemical analysis and compared to controls of HA gels alone and native cartilage. The compressive equilibrium moduli of the p = 0 and p = 1 constructs (51.2 +/- 8.0 and 72.5 +/- 35.2 kPa, respectively) were greater than the p = 2 constructs (26.8 +/- 14.9 kPa) and the control HA gel alone (12.3 +/- 1.3 kPa) and comparable to auricular cartilage (35.1 +/- 12.2 kPa). Biochemical analysis showed a general decrease in glycosaminoglycan (GAG), collagen, and elastin content with chondrocyte passage, though no significant differences were found between the p = 0 and p = 1 constructs for any of the analyses. Histological staining showed intense and uniform staining for aggrecan, as well as greater type II collagen versus type I collagen staining in all constructs. Overall, this study illustrates that constructs with the p = 0 and p = 1 auricular chondrocytes produced neocartilage tissue that resembled native auricular cartilage after 12 weeks in vivo. However, these results indicate that further expansion of the chondrocytes (p = 2) can lead to compromised tissue properties.


Making the next steps in psoriatic arthritis management: current status and future directions.
Psoriatic arthritis (PsA) is a chronic inflammatory condition with articular and extra-articular manifestations: peripheral arthritis, axial disease, enthesitis, dactylitis, and skin and nail disease. It is associated with cardiovascular comorbidities. It is now recognized as a new entity, different from rheumatoid arthritis and other spondyloarthritis in terms of clinical manifestations, pathogenesis, and response to therapies. Anti-tumor necrosis factors (anti-TNFs) have demonstrated clinical efficacies exceeding that of conventional disease modifying antirheumatic drugs (DMARDs). The current treatment paradigms recommend early diagnosis and treatment, and a strategic and target orientated approach, aiming at a low disease activity status. New understanding in the immunopathogenesis of PsA has led to new treatment targets. This review addresses the evidence of current treatment for each of the domains as an aid to the clinician managing these patients in the clinic. Some new therapeutic targets are presented. We highlight the importance of development and validation in outcome measures, including that of composite scores that capture various disease domains that will facilitate future clinical trials to inform the best treatment.


A multicenter trial of enalapril in the treatment of essential hypertension.
The therapeutic profile of enalapril in mild to moderate uncomplicated essential hypertension was assessed in 265 patients who participated in a multicenter, open-label, prospective study lasting eight weeks. There were 54 younger (aged 39 years or less), 136 middle-aged (40 to 59 years), and 75 older patients (60 years or over). Monotherapy with enalapril in a single daily dosage regimen ranging between 5 and 40 mg resulted in normotension (in the sitting position) in 73% of the younger, 50% of the middle-aged, and 56% of the older patients. Normotension was achieved with 5 mg/day of enalapril in 41%, 18%, and 37% of the subgroups, respectively. Both systolic and diastolic pressures at the end of eight weeks of treatment were significantly lower (P less than 0.01) in the younger patients than in the other two age groups. White patients had significantly greater (P less than 0.001) response of both systolic and diastolic blood pressures than did black patients and required significantly smaller (P less than 0.01) average daily dosages of enalapril (14 mg versus 22 mg, respectively). The overall incidence of side effects was 14% among all 276 patients enrolled in the study. Most were mild and transient, but six patients discontinued enalapril during the first week of therapy because of side effects. There were no cases of rash, dysgeusia, hematological disorders, or deterioration in renal function, but there were two cases of pruritus, one of glossitis associated with an upper respiratory infection, and three of dry cough or wheezing. Angioedema was not observed. Monotherapy with enalapril, usually in a single daily dose of 10 to 20 mg, was effective in inducing normotension in approximately half of the middle-aged and older hypertensive individuals and in nearly three fourths of those below age 40. In this study it was generally well tolerated, with a relatively small incidence of side effects.


Nasal chondromesenchymal hamartoma with no nasal symptoms.
The authors present a case of nasal chondromesenchymal hamartoma (NCMH) in an 8-year-old boy with a 4-month history of frontal headache and no symptoms of nasal obstruction, rhinorrhoea or postnasal drip. An ENT examination as well as ophthalmology assessment presented normal results. CT scan showed a lesion involving the sphenoid and ethmoid sinuses. The patient had an endoscopic resection of the lesion that was confirmed histologically to be a NCMH. Though NCMH is known to present usually in infants with obstructing nasal mass, an unusual presentation of a patient with throbbing headache without any nasal symptoms is reported here.


Enhancement of Isotropic Heat Dissipation of Polymer Composites by Using Ternary Filler Systems Consisting of Boron Nitride Nanotubes, h-BN, and Al2O3.
In this research article, a poly(dimethylsiloxane) (PDMS)-based composite was postulated adapting an interactive ternary filler system consisting of Al2O3, hexagonal boron nitride (h-BN), and boron nitride nanotubes (BNNT) to construct a continuous three-dimensional (3D) structure for thermal attenuation. Al2O3 was imposed as a main filler, while h-BN and BNNT were assimilated to form interconnected heat conduction pathways for effective thermal dissipation. The structured framework articulates a profound improvement in isotropic thermal conductivity considering both axial and radial heat dissipation. The presence of h-BN entails uniform heat distribution in a planar mode, eliminating the occurrence of hotspots, while BNNT constructed a connecting phonon pathway in various directions, which insinuates effective overall thermal transport. The generated ternary filler composites attained an isotropic ratio of 1.35 and a thermal conductivity of 7.50 W/mK, which is a 36-fold (∼3650%) increase compared to neat PDMS resin and almost 3-fold (∼297%) that of the Al2O3 unary filler composite and ∼53% that of its binary counterpart, partaking interfacial thermal gaps of ∼36.15 and ∼62.24% on practical heating performance relative to its counterparts. Moreover, the incorporation of BNNT on a traditional spherical and planar filler offers an advantage not only in thermal conductivity but also in thermal and structural stability. Improvement in thermal stability is stipulated due to a melting point (Tm) shift of ∼11 °C upon the assimilation of BNNT. Mechanical permeance reinforcement was also observed with the presence of BNNT, showcasing a 31.5% increase in tensile strength and a 53% increase in Young's modulus relative to the singular filler composite. This exploration administers a new insight into heat dissipation phenomena in polymeric composites and proposes a simple approach to their design and assembly.


Silver Nanoparticles Enhance the Antibacterial Effect of Antibiotic-Loaded Bone Cement.
Purpose The goal of this study was to determine the antibacterial activity of bone cement in polymethyl methacrylate (PMMA) structures with varying amounts of silver nanoparticles (AgNPs) included. Additionally, we aimed to evaluate whether AgNPs affect the biomechanical properties of PMMA cement in our study. Materials and methods Between April 2020 and June 2020, we conducted a series of experiments to demonstrate the antibacterial characteristics by adding silver nanoparticles to PMMA bone cement. PMMA bone cement (Cemex, Tecres Company, Verona, Italy) was used as the base material. Seven different samples were prepared in order to evaluate the amount and presence of AgNPs. Cement samples containing AgNPs and teicoplanin at different concentrations and empty cement (control, without teicoplanin and AgNPs) were placed on Petri plates. The agar diffusion method was used to determine the antibacterial effect (Kirby-Bauer). Results Kirby-Bauer assays demonstrated that AgNPs added to bone cement increased the antimicrobial activity compared to antibiotic-free or only teicoplanin-loaded cement. It was observed that increasing the AgNPs ratio further increased the antimicrobial activity. Conclusion AgNPs in various combinations enhance antimicrobial activity synergistically while maintaining the mechanical strength of bone cement. Increasing the amount of AgNPs results in a significant increase in antimicrobial activity.


Extended Component Separation for Repair of High Ventral Hernia in Pediatric Omphalocele.
Abdominal wall reconstruction ideally involves maintenance of domain by restoration of competent fascia and innervated muscle. Component separation allows closure of ventral hernias, but the technique is limited for high abdominal defects in the epigastric region. We describe an extended component separation that facilitated mobilization of the rectus abdominis muscle along its costal insertion to close an upper midline defect in a child with giant omphalocele, who had already undergone previous traditional component separation.


CSF neurotoxic metals/metalloids levels in amyotrophic lateral sclerosis patients: comparison between bulbar and spinal onset.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of the central nervous system (CNS) that causes progressive and irreversible damage in motor neurons. Different causal hypotheses include genetic, viral, traumatic and environmental mechanisms, such as exposure to heavy metals. The aim of this study was to compare metal/metalloid levels in cerebro-spinal fluid of ALS subtypes (spinal vs bulbar clinical onset). This observational study consecutively screened all ALS patients referring to the Neurology Clinic of the University of Catania (Italy). Inductively coupled plasma mass spectrometry (ICP-MS) was used to quantify magnesium (Mg), cuprum (Cu), selenium (Se), iron (Fe), manganese (Mn), vanadium (V), zinc (Zn), alluminium (Al), arsenic (As), cobalt (Co), nickel (Ni), mercury (Hg), lead (Pb), cadmium (Cd) and palladium (Pd) levels. Thirty-seven patients were enrolled (62.2% females), median age of 65 years (IQR: 59-71 years). Thirty-one (83.8%) patients had a spinal onset and 6 (16.2%) a bulbar onset. Se and As levels were higher compared to the reference values (RV) both in spinal and bulbar onset, while Cu was higher than RV only in bulbar onset. Moreover, Cu (129.8 μg/L vs 29.8 μg/L), Fe (54.5 μg/L vs 33.3 μg/L), Mn (3.4 μg/L vs 1.8 μg/L), Zn (46.1 μg/L vs 35.7 μg/L), Al (12.2 μg/L vs 6.7 μg/L), Ni (2.80 μg/L vs 1.40 μg/L), and Pb (0.60 μg/L vs 0.30 μg/L) levels were higher in bulbar than in spinal onset, conversely As was slightly higher in spinal than in bulbar onset (1.40 μg/L vs 1.10 μg/L). Overall, Cu (129 μg/L vs 31 μg/L), Fe (92.2 μg/L vs 32.9 μg/L), Mn (3.35 μg/L vs 1.80 μg/L), Zn (56.5 μg/L vs 35.2 μg/L), Al (14.45 μg/L vs 6.70 μg/L), and Cd (0.40 μg/L vs 0.08 μg/L) levels were higher in patients with disease duration less than 19 months. Our results supported the hypothesis that metals/metalloids with neurotoxic effects could be involved in the etiology of ALS, showing higher levels of Cu, Se and As. Relevant differences in Cu and Mn levels were found between bulbar and spinal onset patients.


Case report: failure of subcutaneous ivermectin in treating Strongyloides hyperinfection.
A man with Escherichia coli meningitis and bacteremia, while on dexamethasone, developed Strongyloides hyperinfection syndrome and died despite salvage therapy with subcutaneous ivermectin. We report the first documented total and free levels of subcutaneous ivermectin used for therapy.


[Efficacy of neoadjuvant chemotherpy in patients with locally advanced gastric cancer].
To evaluate the efficacy and safety of neoadjuvant chemotherapy in patients with locally advanced gastric cancer, and to analyze the relevant factors of recurrent death of gastric cancer after adjuvant chemotherapy. Clinical data of 49 patients who underwent neoadjuvant chemotherapy for locally advanced gastric cancer between July 2007 and June 2011 were reviewed. Preoperative staging was determined by endoscopic ultrasonography and abdominal computer tomography (CT) or magnetic resonance imaging (MRI). Chemotherapy was administered for regimen of two or three drugs. Prognostic factors were analyzed by univariate and multivariate analysis with Cox proportional hazard model. The response rate was 33.3% (16/48) and disease control rate was 93.8% (45/48). Forty-four (89.8%, 44/49) patients received curative resection after neoadjuvant chemotherapy, among whom 90.9% (40/44) underwent D2 lymphadenctomy. Thirty-two cases had pathological response and 2 patients had pathological complete response. The average hospital stay was 11.6 days and 2 patients had longer hospitalization because of postoperative pancreatic complications. The toxicities were most in grade 1-2. All the patients were followed up postoperatively and the median follow-up was 21.6 months. Median progression-free survival was 29.6 (95%CI:24.0-35.2) months and median overall survival was 34.6 months (95%CI:29.8-39.4). Imaging response (P=0.038, RR=0.168, 95%CI:0.031-0.904) and pathological response (P=0.007, RR=0.203, 95%CI:0.064-0.642) were identified as independent prognostic factors with COX multivariate analysis. Neoadjuvant chemotherapy has quite high disease control rate and R0 resecting rate for patients with locally advanced gastric cancer. Imaging response and pathological response are most important prognostic factors in those patients.


Preparation of mesoporous silica nanoribbons and nanoflakes with short pore channels using a chiral amphiphile.
A chiral cationic low-molecular-weight amphiphile, derived from L-alanine, was synthesized. Templated by the self-assemblies of the amphiphile, sol-gel reactions were carried out to control the morphologies and pore architectures of mesoporous silicas. The results reveal that the morphologies and pore architectures of mesoporous silicas are sensitive to the reaction conditions, such as temperature and the concentration of NaOH. When the reaction was carried out at 25 degrees C, righthanded coiled mesoporous silica nanoribbons with short pore channels were formed, most of which coiled tightly to form nanorods. However, at 80 degrees C, mesoporous silica nanoflakes with vertical pore channels were obtained.


Evaluation of Antiulcer Activity of 80% Methanol Extract and Solvent Fractions of the Root of Croton macrostachyus Hocsht: Ex Del. (Euphorbiaceae) in Rodents.
Peptic ulcer disease causes significant mortality and morbidity. Plant kingdom provides a useful source for the development of new antiulcer agents. Croton macrostachyus is traditionally used to treat peptic ulcer in Ethiopia. This study aimed to evaluate the antiulcer activity of C. macrostachyus root extracts in rodents using different models. The crude extract was obtained by cold maceration in 80% methanol and fractionated with chloroform, ethyl acetate, and distilled water. The antiulcer activity was evaluated using pylorus ligation-induced ulcer model in Sprague Dawley rats and acidified ethanol-induced ulcer model in Swiss albino mice. The test groups received three doses (100, 200, and 400 mg/kg) of the crude extract and fractions for 7 days before induction of ulcer. Positive controls received omeprazole 30 mg/kg for the pylorus ligation-induced ulcer model and sucralfate 100 mg/kg for the acidified ethanol-induced ulcer model. Negative controls received vehicle (2% tween 80). The crude hydromethanolic extract of C. macrostachyus showed significant (p < 0.05) antiulcer activity on both pyloric ligation and HCl/ethanol-induced ulcer in rats and mice. It has antisecretary effect (p < 0.001) as well. All three administered doses of chloroform fraction (p < 0.05) and only higher doses of ethyl acetate fraction (p < 0.05) possessed significant antiulcer activity. In contrast, the aqueous fraction did not have significant antiulcer effect at all tested doses. The present study demonstrated that the crude extract, chloroform, and ethyl acetate fractions possessed significant dose-dependent antiulcer activity.


Stenope, a new euphorine genus from the Philippines (Hymenoptera: Braconidae).
A new genus (Stenope gen. nov.; type species: Allophrys falcatus) is described for the aberrant type species from the Philippines accidently described as an ichneumonid species.


Generation of glycosylphosphatidylinositol linked chicken IL-17 to generate specific monoclonal antibodies applicable for intracellular cytokine staining.
Interleukin 17 (IL-17) cytokines play a crucial role in host defense and inflammatory diseases. Of the six mammalian IL-17 members five are described in the chicken (gg) genome. A novel method that attached cytokines to the surface of cells via a GPI linker was established to generate two chicken IL-17A and one chicken IL-17F specific mab. Recombinant gg IL-17A and gg IL-17F that showed dimerization in Western blot were used to verify the antibodies specificity. The mab could detect gg IL-17 by intracellular cytokine staining as demonstrated on cells expressing recombinant IL-17. Furthermore IL-17A and lower amounts of IL-17F were detectable in CD4 positive T cells of stimulated splenocytes. In conclusion, we have generated novel tools to analyze chicken IL-17 in more detail and demonstrated that the surface expression of cytokines is a reliable method to generate specific mab applicable for intracellular cytokine staining.


Biological evaluation of a novel sorafenib analogue, t-CUPM.
Sorafenib (Nexavar®) is currently the only FDA-approved small molecule targeted therapy for advanced hepatocellular carcinoma. The use of structural analogues and derivatives of sorafenib has enabled the elucidation of critical targets and mechanism(s) of cell death for human cancer lines. We previously performed a structure-activity relationship study on a series of sorafenib analogues designed to investigate the inhibition overlap between the major targets of sorafenib Raf-1 kinase and VEGFR-2, and an enzyme shown to be a potent off-target of sorafenib, soluble epoxide hydrolase. In the current work, we present the biological data on our lead sorafenib analogue, t-CUPM, demonstrating that this analogue retains cytotoxicity similar to sorafenib in various human cancer cell lines and strongly inhibits growth in the NCI-60 cell line panel. Co-treatment with the pan-caspase inhibitor, Z-VAD-FMK, failed to rescue the cell viability responses of both sorafenib and t-CUPM, and immunofluorescence microscopy shows similar mitochondrial depolarization and apoptosis-inducing factor release for both compounds. These data suggest that both compounds induce a similar mechanism of caspase-independent apoptosis in hepatoma cells. In addition, t-CUPM displays anti-proliferative effects comparable to sorafenib as seen by a halt in G0/G1 in cell cycle progression. The structural difference between sorafenib and t-CUPM significantly reduces inhibitory spectrum of kinases by this analogue, and pharmacokinetic characterization demonstrates a 20-fold better oral bioavailability of t-CUPM than sorafenib in mice. Thus, t-CUPM may have the potential to reduce the adverse events observed from the multikinase inhibitory properties and the large dosing regimens of sorafenib.


Copper-catalyzed enantioselective 1,4-addition to alpha,beta-unsaturated aldehydes.
The first asymmetric Cu-catalyzed conjugate addition of dialkylzinc zinc reagents to a large scope of enals in presence of phosphoramidite, SimplePhos, or (R)-BINAP ligands with enantiomeric excesses up to 90% is reported. Moreover, ACA of Grignard reagents afforded moderate to good 1,4-regioselectivities with enantioselectivities up to 90%.


Detection of leukotriene C4-liked immunoreactivity in tear fluid from subjects challenged with specific allergen.
Tear fluid was obtained from allergic subjects from control eyes and eyes challenged with specific allergen and levels of leukotriene C4 (LTC4)-immunoreactivity determined by radioimmunoassay. Formal identification of the leukotrienes released was not possible but the levels of LTC4-immunoreactive material in allergen-challenged tear fluid (4.9 +/- 2.3 ng/ml, n = 9) were significantly higher (p less than 0.01) than those in control tear fluid (0.07 +/- 0.06 ng/ml, n = 9). These results provide evidence that leukotrienes, which account for the biological activity of slow reacting substance of anaphylaxis, may be released in allergic reactions in vivo in man.


Quality assurance in health care: missions, goals, activities.
The most challenging mission of medical personnel today is quality assurance in health care. To meet this challenge, the essential elements of a six-phase system for total quality control for the medical laboratory are outlined under the headings of design control, incoming material control, process control, output control, reliability control, and special verification studies. Review of existing goals and activities of programs related to this mission indicates both problems and rich opportunities for individual laboratory professionals and their organizations. For effective implementation of this mission, the laboratory professionals will have to create the atmosphere of a collegium where all interested scientists communicate across disciplines to eliminate the systematic biases and improve the accuracy, precision, and specificity of clinical laboratory measuring systems, to assure medically meaningful and useful assay results for the broad spectrum of health care that is necessary for the well, the near-well, and the sick.


Subcoracoid dislocation of the distal end of the clavicle. A case report.
Subcoracoid dislocation of the outer end of the clavicle in association with an acromial fracture is a rare injury usually produced by high energy trauma that moves the clavicle posterior to the conjoined tendon and inferior to the coracoid process. To restore the acromioclavicular joint, open reduction is needed. After the reduction is accomplished, the clavicle has to be stabilized with a coracoclavicular screw. The acromial fracture can be reduced and held with nonabsorbable sutures placed through the bone. To avoid osteolysis of the distal end of the clavicle and to be able to repair the torn ligaments, treatment should not be delayed.


[The Influence of Preoperative Oral Carbohydrate Administration on Perioperative Blood Sugar Levels and Patients' Satisfaction].
After introducing preoperative oral carbohydrate as a part of enhanced recovery after surgery (ERAS) protocols, we assessed the influence of carbohydrate administration on the perioperative blood sugar levels (BS), the variation of vital signs and patients' satisfaction. After IRB's approval and obtaining patients' consent, patients were divided into two groups; taking carbohydrate (Group AW) or not (Group NAW). Anesthesia was induced and maintained with total intravenous anesthesia using propofol, remifentanil and rocuronium. We measured BS six times during perioperative period. We also compared blood pressures and heart rates during induction of anesthesia. Moreover, we carried out questionnaire surveys about degree of satisfaction for ERAS among patients and nurses. Heart rates were significantly higher in Group AW (P < 0.05), but there were no significant difference in blood pressures or BS between the groups. Patients in Group AW had more anxiety for surgeries (P = 0.003), but more than 85% of patients and nurses were satisfied with carbohydrates. The carbohydrate administration had little influence on the perioperative vital signs. However, we gained high reputations from patients and paramedics.


Effects of atmospheric low-level jets on the mixing process of a large tropical reservoir.
Changes in the physical and biogeochemical properties of water columns are frequently associated with cold fronts and mesoscale convective systems due to increased cloud cover. The effects of low-level jet (LLJ) events on thermal stratification and water quality, however, remain undescribed, particularly for tropical reservoirs. Here, water temperature time series are combined with meteorological data, LIDAR observations, ERA5 reanalysis data, and hydrodynamical modeling to investigate the impact of an event of LLJ over the Furnas hydropower reservoir in Brazil. The LLJ event was characterized by dry, intense, and persistent winds (~10 m s-1) blowing for more than 12 hours over the main fetch of the reservoir. In the downwind side of the lake, the surface mixed layer depth increased by 50% during the LLJ event. The changes to the water column were produced by a combination of wind-induced upwelling, shear-driven mixing, and nocturnal convective overturning, different from the heat balance expected during passing cold fronts and mesoscale convective systems. The results suggest that both momentum and heat fluxes during LLJ events need to be accounted for in lake modelings to reproduce the vertical mixing process.


Pocket2Drug: An Encoder-Decoder Deep Neural Network for the Target-Based Drug Design.
Computational modeling is an essential component of modern drug discovery. One of its most important applications is to select promising drug candidates for pharmacologically relevant target proteins. Because of continuing advances in structural biology, putative binding sites for small organic molecules are being discovered in numerous proteins linked to various diseases. These valuable data offer new opportunities to build efficient computational models predicting binding molecules for target sites through the application of data mining and machine learning. In particular, deep neural networks are powerful techniques capable of learning from complex data in order to make informed drug binding predictions. In this communication, we describe Pocket2Drug, a deep graph neural network model to predict binding molecules for a given a ligand binding site. This approach first learns the conditional probability distribution of small molecules from a large dataset of pocket structures with supervised training, followed by the sampling of drug candidates from the trained model. Comprehensive benchmarking simulations show that using Pocket2Drug significantly improves the chances of finding molecules binding to target pockets compared to traditional drug selection procedures. Specifically, known binders are generated for as many as 80.5% of targets present in the testing set consisting of dissimilar data from that used to train the deep graph neural network model. Overall, Pocket2Drug is a promising computational approach to inform the discovery of novel biopharmaceuticals.


The role of light wavelengths in regulating algal-bacterial granules formation, protein and lipid accumulation, and microbial functions.
High value-added products recovery from algal-bacterial granular sludge (ABGS) has received great attention recently. This study aimed to explore the role of different light wavelengths in regulating granule formation, protein and lipid production, and microbial functions. Bacterial granular sludge (BGS, R0) was most conducive to forming ABGS under blue (R2) light with the highest chlorophyll a (10.2 mg/g-VSS) and diameter (1800 μm), followed by red (R1) and white (R3) lights. R0-R3 acquired high protein contents (>164.8 mg/g-VSS) with essential amino acids above 44.4%, all of which were suitable for recycling, but R2 was the best. Also, blue light significantly increased total lipid production, while red light promoted the accumulation of some unsaturated fatty acids (C18:2 and C18:3). Some unique algae and dominant bacteria (e.g., Stigeoclonium, Chlamydomonas, and Flavobacteria) enrichment and some key functions (e.g., amino acid, fatty acid, and lipid biosynthesis) up-regulation in R2 might help to improve proteins and lipids quality. Combined, this study provides valuable guidance for protein and lipid recovery from ABGS.


Activation of c-Jun by human cytomegalovirus UL42 through JNK activation.
c-Jun is a major component of the AP-1 transactivator complex. In this report, we demonstrated that AP-1 was activated by the expression of UL42, a human cytomegalovirus-encoded membrane protein that has two PPXY (PY) motifs and a C-terminal transmembrane domain (TMD). Although UL42 interacts with Itch, an ubiquitin E3 ligase, through the PY motifs, UL42 phosphorylated c-Jun and c-Jun N-terminal kinase (JNK) in the absence of any interaction with Itch. Experiments using mutated versions of UL42 suggest the importance of the carboxyl half (a.a. 52-124) of UL42 for the activation of the JNK signaling, while C-terminal TMD alone is not sufficient. Thus, we hypothesize that UL42 plays a role in the activation of JNK signaling in HCMV-infected cells. (118 words).


Suicide-related crimes in contemporary European criminal laws.
This article describes suicide-related penal legislation in contemporary Europe, and analyzes and relates the results to cultural attitudes towards suicide and to national suicide rates. Data were obtained from 42 legal entities. Of these, 34 have penal regulations which--according to definition--chiefly and directly deal with suicide. There are three main types of act: aiding suicide, abetting suicide, and driving to suicide. The laws vary considerably with regard to which acts are sanctioned, how severely they are punished, and whether any special circumstances such as the motive, the result, or the object can make the crime more serious. Various ideologies have inspired legislation: religions, the euthanasia movement, and suicide prevention have all left their mark. There are some cases in which neighboring legal systems have clearly influenced laws on the topic. However, the process seems mostly to have been a national affair, resulting in surprisingly large discrepancies between European legal systems. The laws seem to reflect public opinions: countries which punish the crimes harder have significantly less permissive cultural attitudes towards suicide. Likewise, suicide rates were significantly higher in countries with a narrow scope of criminalization and milder punishments for suicide-related crimes. The cultural and normative elements of society are connected with its suicide mortality.


[RETROPERITONEAL LIPOSARCOMA WITH MULTIPLE RECURRENCE OF LUNG METASTASES TREATED BY MULTIMODAL THERAPY CENTERING ON THE OPERATION: A CASE REPORT].
A 34-year-old man presented with scrotal pain and slight fever. The scrotal pain was improved by the treatment of antibiotics, but the slight fever remained and an abdominal protuberance appeared. Computed tomography showed a 22 cm abdominal tumor with lipid density. He was then referred to our hospital. He was diagnosed as retroperitoneal liposarcoma and a surgical resection was performed for retroperitoneal tumor and surrounding organs. Histopathological diagnosis was dedifferentiated liposarcoma. 3 months after surgery, a PET/CT scan showed multiple lung metastases. We treated the patient with AI therapy by doxorubicin and ifosfamide. After 6 courses were performed, a complete response was achieved. 30months after the initial surgery, a PET/CT scan showed there was just one metastasis which was in the left lung. Thoracoscopic lung tumor resection was performed. Histopathological diagnosis was metastatic dedifferentiated liposarcoma. As adjuvant therapy, we treated with IE therapy by ifosfamide and VP-16. 3 courses were performed. 3 years and 6 months after the first surgery, he has had no recurrence up to the present day.


Beyond skin feel: innovative methods for developing complex sensory profiles with silicones.
In today's competitive skin care market, formulators strive to meet consumer demand for products that combine performance with superior esthetics. Although skin feel has always been a key esthetic parameter, consumers increasingly select products based on a more complete sensory experience, including texture, scent, visual esthetics in the container, tactile effects on application, and the performance of active ingredients such as vitamins or sunscreen. This paper reviews approaches employed by Dow Corning which, when combined with sensory evaluation and formulation expertise, can be used to develop a more complete sensory experience, respond to consumer trends, or meet specific regional preferences for skin care products. It also describes how silicones can be used to develop new product appearance, texture, skin appearance, and feel, based on the wide range of rheological behavior and product forms among these materials.


Effects of Resveratrol on Inflammation and Apoptosis After Experimental Spinal Cord Injury.
To determine the effects of resveratrol on inflammation and apoptosis after experimental spinal cord injury (SCI). Eighteen Sprague-Dawley rats were randomly divided into three groups. All groups underwent thoracic laminectomy. The first group received no other intervention. The second and third groups suffered SCI via the aneurysm clip compression method, and additionally the third group received resveratrol. After euthanizing the rats, immunohistochemical analysis and biochemical parameters of tumor necrosis factor alpha (TNF-?) and interleukin (IL)-1? were measured. The resveratrol group had statistically significant lower levels of TNF-?, IL -1?, and terminal deoxynucleotidyl transferasemediated dUTP nick-end labeling (TUNEL) positive cells and higher number of glial and motor neuron cells. Resveratrol proves to have remarkable neuroprotective effects on SCI in an experimental model in addition to its proven cardioprotective effects.


Inflammatory reactions induced by pretransplant conditioning--an alternative target for modulation of acute GvHD and complications following allogeneic bone marrow transplantation?
Intensity of pretransplant conditioning has been closely correlated with regimen related toxicity in patients receiving allogeneic bone marrow transplantation (BMT). In this review, we summarize evidence for a direct link between inflammatory reactions induced by irradiation and cytotoxic treatment and occurrence of acute graft-versus-host disease (GvHD) as well as endothelial complications: In our studies, de novo release of TNFalpha during conditioning was associated with an increased risk of severe GvHD and mortality following BMT, whereas increased spontaneous production of IL-10, an endogenous TNF-antagonist, prior to conditioning protected from these complications. Immunogenetic differences in cytokine regulation and costimulation by endotoxin proved to be important cofactors determining the extent of inflammatory cytokine release in individual patients. Pathophysiological relevance of these findings seems to be confirmed by experimental as well as first clinical trials using TNF-antibodies and related antagonists during pretransplant conditioning. Preclinical experiments suggest additional, cytokine independent inflammatory reactions induced by irradiation such as expression of ICAM-1 and endothelial cell apoptosis. Although the exact impact of these findings on pathophysiology of BMT related complications needs further clarification by future studies, conditioning related inflammation as a first crucial step in induction of GvHD and complications has to be considered when designing new protocols for preparation of patients for allogeneic BMT.