Epithelial membrane protein 2: a novel biomarker for circulating tumor cell recovery in breast cancer.
EpCAM is a common marker used in the detection of circulating tumor cells (CTC). Disseminated cancer cells display the characteristics of epithelial-to-mesenchymal transition events. The purpose of this study was to assess the potential of epithelial membrane protein 2 (EMP2) as a novel biomarker for CTC retrieval in breast cancer. MCF7 and MDA-MB-231 cells were stained with either anti-EpCAM or anti-EMP2 mAbs, respectively, followed by flow cytometric assay to measure their expression levels. PBMCs isolated from healthy donors were used for breast cancer cell spiking. CD45-depleted PBMCs from breast cancer patients' blood were used for CTC capturing. Immunomagnetic separation was used to enrich breast cancer cells. Cytospin centrifugation was performed to concentrate the captured cells, followed by immunofluorescence staining with anti-CD45 mAb, anti-pan cytokeratin mAb and DAPI. Fluorescent images were taken using a confocal microscope for CTC counts. MDA-MB-231 cells had 2.56 times higher EMP2 expression than MCF7 cells, and EMP2 had a significantly higher capture efficiency than EpCAM for MCF7 cells. Furthermore, anti-EMP2 was capable of capturing MCF7 cells that escaped in the flow-through of anti-EpCAM. Likewise, EMP2 had a significantly higher capture efficiency on MDA-MB-231 cells when compared to MCF7 cells. Most importantly, EMP2 biomarker was successfully used for CTC capture in patients with primary breast cancer. EMP2 is superior to EpCAM for capturing both MCF7 and MDA-MB-231 cells. Additionally, EMP2 is a novel biomarker and capable of capturing breast cancer cells in patient blood samples.


Effects of the synthetic cannabinoid nabilone on spatial learning and hippocampal neurotransmission.
Cannabinoids, the active components of marijuana, affect memory and hippocampal neurotransmission. It has been claimed that nabilone, a synthetic cannabinoid endowed with antiemetic properties, has a peculiar profile of actions. We studied the effects of the drug on spatial learning and in vitro hippocampal CA1 electrophysiology in the rat. Nabilone (0.1, 0.5, and 1.0 mg/kg ip) does not impair place learning in a water maze task, whereas Delta(8)-tetrahydrocannabinol (Delta(8)-THC) disrupts this function. At concentrations ranging from 1 nM to 10 microM nabilone does not influence basal glutamatergic neurotransmission, which is decreased by Delta(8)-THC. Although cannabinoids have been consistently reported to affect synaptic plasticity, nabilone 1 microM does not change paired-pulse facilitation, long-term potentiation and the magnitude of long-term depression. However, the time course of the latter phenomenon is significantly changed by the drug, the depression being lower than in control experiments from 7 to 35 min postinduction. Altogether, our data indicate that there might be differences in the effects of agonists for central cannabinoid receptors, which could help to understand the pharmacology of this class of molecules. The results also suggest that amnesia induced by cannabinoids be possibly related to their effects on hippocampal neurotransmission. The study supports the use of nabilone in conditions the course of which is complicated by cognitive impairment.


Effects of protein synthesis inhibition on low molecular weight RNA metabolism in tsH1, a mutant cell line with a temperature-sensitive leucyl-tRNA synthetase.
The effect of inhibition of protein synthesis on the synthesis and processing of low molecular weight RNA (LMW RNA) hs been studied on CHO-tsH1, a mutant cell line in which protein synthesis is rapidly inhibited at non-permissive temperature by inactivation of the enzyme leucyl-tRNA synthetase. The increase in temperature results in an increase in uridine uptake and in the specific activity of UTP pool which is probably not related to the mutation. We report in this paper that there is no significant alteration in the synthesis of LMW RNA (including 5S ribosomal RNA (rRNA) and tRNA) except for the inhibition of synthesis of nucleolar RNA species A. Since, in a previous paper, it has been shown that the processing of preribosomal nucleolar RNA does not proceed at 39.5 degrees C in CHO-tsH1 cells, these results are consistent with the hypothesis that nucleolar RNA species A is involved in the processing of rRNA depends on its synthesis and maturation.


Spiral-Structured Dielectric Polymers Exhibiting Ultrahigh Energy Density and Charge-Discharge Efficiency at High Temperatures.
The growing need for high-power and compact-size energy storage in modern electronic and electrical systems demands polymer film capacitors with excellent temperature capability. However, conventional polymer dielectrics feature dramatic deterioration in capacitive performance under concurrent high temperature and electric field because the high thermal stability traditionally relies on the conjugated, planar molecular segments in the polymer chains. Herein, inspired by the stable double helix structures of deoxyribonucleic acid, spiral-structured dielectric polymers that exhibit simultaneous high thermal stability and great capacitive performance are demonstrated. Both the experimental results and computational simulations confirm that the spiral groups serve to weaken the electrostatic molecular interaction, induce proper molecular chain stacking structure, and regulate the charge transfer process by breaking the conjugated planes and introducing deep trap sites. The resultant polymer exhibits the maximum discharged energy densities of 7.29 and 6.13 J cm-3 with the charge-discharge efficiency above 90% at 150 and 200 °C, respectively, more than ten times those of the original dielectric at the same conditions. Here a completely new dimension is offered for the molecular design of polymers, giving rise to well-balanced thermal and dielectric properties, and ultimately the desired capacitive energy storage performance at high temperatures.


Candida albicans isolation from buccal mucosa of patients with HIV wearing removable dental prostheses.
The aim of this study was to evaluate the influence of complete or partial removable dental prostheses (RDPs) on the frequency of Candida albicans isolated from the mouth and the presence of oral candidiasis in human immunodeficiency virus-positive (HIV+) patients correlated with CD4 levels. One hundred ninety-three HIV+ patients were evaluated; 68 had RDPs and 125 did not. CD4 cell count was obtained after blood sampling and performed on the day of clinical examination. The material was collected from the buccal mucosa for isolation of yeasts with a sterile swab and seeded onto Sabouraud dextrose agar with chloramphenicol. C albicans strains were identified by testing germ tubes and chlamydospore formation and biochemical (zymogram, auxanogram) characteristics. The results were subjected to the Fischer exact test and chi-square tests. C albicans were isolated from 45 (66.17%) patients who had RDPs and 48 (38.4%) who did not (P = .0003). The presence of oral candidiasis was observed in 14 patients (7.25%), and 10 of the 14 (71.43%) were RDP users. The absence of candidiasis occurred in 121 (67.59%) nonusers and 58 (32.40%) users of RDPs (P = .0065). The mean CD4 cell count was lower in patients with oral candidiasis regardless of the use of RDPs. The use of RDPs was an important factor in the isolation of C albicans among HIV+ patients, and CD4 level seems to play a role in the presence of oral candidiasis.


Therapeutic isoniazid monitoring using a simple high-performance liquid chromatographic method with ultraviolet detection.
Simultaneous measurement of isoniazid and its main acetylated metabolite acetylisoniazid in human plasma is realized by high-performance liquid chromatography. The technique used is evaluated by a factorial design of validation that proved to be convenient for routine drug monitoring. Plasma samples are deproteinized by trichloroacetic acid and then the analytes are separated on a microBondapak C18 column (Waters). Nicotinamide is used as an internal standard. The mobile phase is 0.05 M ammonium acetate buffer (pH 6)-acetonitrile (99:1, v/v). The detection is by ultraviolet absorbance at 275 nm. The validation, using the factorial design allows one to: (a) test the systematic factors of bias (linearity and matrix effect); (b) estimate the relative standard deviations (RSDs) related to extraction, measure and sessions assay. The linearity is confirmed to be within a range of 0.5 to 8 microg/ml of isoniazid and 1 to 16 microg/ml of acetylisoniazid. This method shows a good repeatability for both extraction and measurement (RSD INH=3.54% and 3.32%; RSD Ac.INH=0.00% and 5.97%), as well as a good intermediate precision (RSD INH=7.96%; RSD Ac.INH=15.86%). The method is also selective in cases of polytherapy as many drugs are associated (rifampicin, ethambutol, pyrazinamide, streptomycin). The matrix effect (plasma vs. water) is negligible for INH (3%), but statistically significant for Ac.INH (11%). The application of this validation design gave us the possibility to set up an easy and suitable method for INH therapeutic monitoring.


Microbial production and biotechnological applications of α-galactosidase.
α-Galactosidase, (E.C. 126.96.36.199) is an exoglycosidase that target galactooligosaccharides such as raffinose, melibiose, stachyose and branched polysaccharides like galactomannans and galacto-glucomannans by catalysing the hydrolysis of α-1,6 linked terminal galactose residues. The enzyme has been isolated and characterized from microbial, plant and animal sources. This ubiquitous enzyme possesses physiological significance and immense industrial potential. Optimization of the growth conditions and efficient purification strategies can lead to a significant increase in the enzyme production. To boost commercial productivity, cloning of novel α-galactosidase genes and their heterologous expression in suitable host has gained popularity. Enzyme immobilization leads to its greater reutilization, superior thermostability, pH tolerance and increased activity. The enzyme is well explored in food industry in the removal of raffinose family oligosaccharides (RFOs) in soymilk and sugar crystallization process. It also improves animal feed quality and biomass processing. Applications of the enzyme is in the area of biomedicine includes therapeutic advances in treatment of Fabry disease, blood group conversion and removal of α-gal type immunogenic epitopes in xenotransplantation. With considerable biotechnological applications, this enzyme has been vastly commercialized and holds greater future prospects.


2-Hy-droxy-ethyl-ammonium [2-(2,6-di-chloro-anilino)phen-yl]acetate monohydrate.
In the solid-state structure of the title compound derived from diclofenac, C2H8NO+·C14H10Cl2NO2 -·H2O, the asymmetric unit contains one cation, one anion and a water mol-ecule, all in general positions. A complex network of hydrogen bonds is present in the crystal structure.


Extracorporeal shock wave lithotripsy for urinary stone disease: clinical experience with the electromagnetic lithotriptor 'Lithostar'.
400 urinary stone patients were treated with the electromagnetic lithotriptor Siemens 'Lithostar': 66.3% had renal stones and 33.7% had ureteral stones. Ninety percent of the treatments were performed under intravenous sedation only: 14.5% of the patients had more than one session. After 3 months more than 80% of the patients with a single stone smaller than 1.5 cm and 46% of the patients with stones larger than 2.5 cm were 'stone-free'.


Association of pain relief with drug side effects in postherpetic neuralgia: a single-dose study of clonidine, codeine, ibuprofen, and placebo.
In a randomized, double-blind crossover study, 40 patients with postherpetic neuralgia were given single oral doses of clonidine, 0.2 mg, codeine, 120 mg, ibuprofen, 800 mg, or inert placebo. Pain relief and side effects were recorded for 6 hours. Patients reported significantly more relief after clonidine than after the other three treatments. Codeine and ibuprofen were ineffective. Sedation, dizziness, and other side effects were more frequent after clonidine (74%) or codeine (69%) than after placebo (36%) or ibuprofen (28%). Reported pain relief was greater during trials in which side effects were present. A single, mild side effect was associated with as much additional pain relief as multiple, severe side effects. Clonidine's superiority to codeine, which had a similar incidence of side effects, argues for a specific analgesic effect. In addition, side effects may have contributed to clonidine analgesia, perhaps by suggesting to patients that they had received a potent drug.


Antioxidant effect of propolis against exposure to propetamphos in rats.
In the present study, each group comprised six animals, and a total of 30 female. Wistar Albino rats weighing 200-250g were used. The first group served as the control group. Group 2 received propolis at a concentration of 100mg/kgbw/day in drinking water. Groups 3 and 4 were administered propetamphos at doses of 7.5 and 15.0mg/kgbw/day, respectively, in drinking water. Group 5 was treated with propetamphos at a dose of 15.0mg/kgbw/day, in association with 100mg/kgbw/day propolis in drinking water. Treatment was continued for 28 days, and at the end of this period, blood and tissue (liver, kidney and brain) samples were collected. Plasma and tissue MDA levels and erythrocyte and tissue SOD, CAT, and GSH-Px activities were measured. In conclusion, the administration of propolis was concluded to exhibit antiradical and antioxidant effect, and thereby to result in the alleviation of oxidative stress.


Age at onset of major depression in inner-city adults with asthma.
Depression generally begins before Type II diabetes and coronary artery disease; however, no data are available on whether asthma or major depressive disorder (MDD) have an earlier onset. The age at onset of asthma and depression were collected from 85 adult asthma patients with current MDD. The mean ages at onset of asthma and MDD were 21.0 years and 28.8 years, respectively. Asthma preceded MDD in 62% of cases; MDD preceded asthma onset in 24% of cases; and asthma and MDD had a concurrent onset in 14% of the cases. In asthma patients, unlike patients with Type II diabetes and coronary artery disease, depression appears generally to occur after the onset of asthma.


Laparoscopic intracorporeal cinch knots: changing the square knot paradigm.
Reliable knot tying is a cornerstone of surgical technique, and the square knot and surgeon's knot constitute the greatest part of most surgeons' knot-tying skills. Traditionally, laparoscopic intracorporeal knot tying of a square knot or surgeon's knot is a direct translation from an open instrument tying technique. Given the technical and mechanical challenges imposed by standard laparoscopic instrumentation, performance of such a basic task is sometimes difficult and elusive, even for accomplished surgeons. Consequently, myriad technologies and techniques are used as work-arounds for this basic surgical task. However, the sometimes necessary tying of a snug and reliable intracorporeal knot is unavoidable. That laparoscopic intracorporeal knot tying must be translated from a 2-handed open surgical technique using flat knots deserves reassessment. Cinch knots, with unusual sliding and tightening properties, are currently used in surgery. With apparent complexity and exacting construction requirements, however, primary intracorporeal knot tying has not been described. Described herein is a technique for doing so. Also included is a review of cinch knot mechanics, an understanding of a fundamental scheme for their construction, and basic instrument maneuvers that enable easier intracorporeal tying of a most reliable knot, useful for multiport and, in particular, single-port laparoscopic knot tying.


Simultaneous analysis of chlorophenols, alkylphenols, nitrophenols and cresols in wastewater effluents, using solid phase extraction and further determination by gas chromatography-tandem mass spectrometry.
An analytical methodology has been developed for the simultaneous extraction of 13 phenolic compounds, including chlorophenols (CPs), nitrophenols (NTPs), cresols and alkylphenols (APs) in different types of wastewater (WW) effluents. A solid-phase extraction (SPE) method has been optimized prior to the determination by gas chromatography coupled to triple quadrupole tandem mass spectrometry (GC-QqQ-MS/MS). Due to the complexity of the matrix, a comparison study of matrix-matched-calibration (MMC) and standard addition calibration (SAC) was carried out for quantification purposes. The optimized procedure was validated using the SAC approach since it provided the most adequate quantification results (in terms of recovery and precision values). Recoveries were in the range 60-135% (0.5 μg L(-1)), 70-115% (1 μg L(-1)), and 78-120% (5 μg L(-1)), with precision values (expressed as relative standard deviation, RSD) ≤ 30% (except for 2-nitrophenol) involving intra-day and inter-day precision studies. Limits of detection (LODs) and quantification (LOQs) were also evaluated, and LOQs ranged from 0.03 μg L(-1) to 2.5 μg L(-1). The proposed method was applied to the analysis of 8 real WW effluent samples, finding some phenolic compounds (e.g. 2-chlorophenol, 2,4,6-trichlorophenol and 4-tert-octylphenol) at concentrations higher than the established LOQs.


Intracellular iron storage and the pathogenesis of paratuberculosis. Comparative studies with other mycobacterial, parasitic or infectious conditions of veterinary importance.
The distribution of iron and mycobacteria was examined in the intestinal tract of ruminants with naturally-occurring M. paratuberculosis infection and compared with mycobacterial infections in several species. This distribution was compared with that of iron in chronic lesions caused by other microbial or parasitic agents. In the clinical form of paratuberculosis in cattle, sheep and goats there was marked lymphangiectasis and a high proportion of the granulomatous lesions contained siderotic macrophages with a high mycobacterial content. In cattle with preclinical lesions of granulomatous enteropathy, the greatest number of acid-fast organisms was present in siderotic, non-differentiated, ileo-caecal macrophages; concurrent mast cell-associated allergic enteropathy was also apparent in the duodenum, proximal and mid-ileum of most animals. In paratuberculosis-affected herds, a high proportion of non-productive cows were without classical granulomatous change but had cultural or immunological evidence of M. paratuberculosis infection and similar allergic catarrhal enteropathy of the upper intestinal tract. Interstitial haemorrhage of the ileocaecal valve, with the accumulation of haemosiderin and ferritin in undifferentiated macrophages was observed in some of these cattle and also in others with experimentally-induced copper deficiency and acute ostertagiasis. Colonisation of the ileo-caecal or caecal glandular crypts by large, apparently saprophytic acid-fast organisms indicated regional tolerance to such organisms in all cattle. In other mycobacterioses such as bovine or avian tuberculosis, undifferentiated, siderotic macrophages containing mycobacteria were also seen in early granulomas, but epithelioid and giant cell differentiation invariably led to the disappearance of intracellular iron and a reduction in mycobacterial numbers. In possums in which epithelioid and giant cells did not occur in response to M. bovis infection, siderosis persisted in many macrophages and overwhelming mycobacterial multiplication occurred. These studies indicate that, in most infections with mycobacteria, differentiation of macrophages radically reverses their iron acquisitive properties, creating an intracellular environment unsuitable for mycobacterial multiplication. It seems likely that allergically mediated microvascular haemorrhage, local tolerance of commensal mycobacteria and attenuation of the macrophage siderosis reversal mechanism provide unique conditions for early, uninhibited, intracellular multiplication of M. paratuberculosis in the ileo-caecal valve of certain mature ruminants.


Angiogenic profiling in HELLP syndrome cases with or without hypertension and proteinuria.
Angiogenic profiling with the use of sFlt-1/PlGF ratio (soluble fms-like tyrosine kinase-1/placental growth factor) can be helpful to characterize women with signs of impending preeclampsia (PE). However, little is known about the angiogenic profile of pregnancies complicated by HELLP syndrome. The aim of this study was to examine the relationship of angiogenic profiles in cases of HELLP syndrome with and without classical signs of preeclampsia. The angiogenic profile of pregnant women with singleton gestation and isolated PE (group 1), PE associated with HELLP syndrome (group 2), and isolated HELLP syndrome (group 3) from 01/2011 to 03/2018, were compared. To overcome gestational age dependent angiogenic behavior, cases (group 3) were matched 1:2 with cases from group 1 and 2. Matching criteria was gestational age (±1 week). PE and HELLP syndrome were defined according to the international Society for the Study of Hypertension in Pregnancy (ISSHP) statement 2014. During the observational period, 244 women could be included in the study. Of those, 237 (97.1%) were diagnosed with PE. In 42 cases (17.2%) PE was associated with HELLP syndrome while 7 (2.9%) patients were diagnosed with isolated HELLP syndrome. Angiogenic profiles in terms of sFlt-1/PlGF ratios differed significantly between the three groups, showing highest levels in group 2 (PE/HELLP) while cases with isolated HELLP demonstrated the lowest ratios and sFlt-1 values (p = 0.01). We conclude that isolated HELLP syndrome is rare and seems to be a particular entity expressing a different angiogenic behaviour compared to classical PE or PE associated with HELLP syndrome.


Positive and negative romantic relationship quality: age, familiarity, attachment and well-being as correlates of couple agreement and projection.
Capturing the multiple aspects of the romantic peer context is a significant challenge for research. One often recommended option is to use reports of multiple relationship features from both members of the romantic dyad. Using a new measure, we extended an existing model of dyadic perception (Kenny & Acitelli, 2001) to investigate associations between couples' (N = 148) reports about the positive and negative dimensions of their romantic relationships. Differences by participant age and relationship length were examined to test developmental hypotheses, and attachment and well-being were examined as correlates of participants' romantic perceptions. Agreement between partners was low, but associations of individuals' reports about themselves and their partners were high (projection). Agreement about negative romantic behaviors was higher in older compared to younger individuals and agreement about positive behaviors was higher in longer compared to shorter relationships. Partner similarity in negative behavior was higher than similarity in positive behavior. Individuals with better well-being reported more positive romantic behaviors, and attachment security was associated in some cases. Males were more negative about romantic behaviors than females, but there was no gender difference in agreement or projection.


DNA methylation derived systemic inflammation indices are associated with head and neck cancer development and survival.
Head and neck squamous cell carcinoma (HNSCC) is often associated with chronic systemic inflammation (SI). In the present study, we assessed if DNA methylation-derived SI (mdSI) indices: Neutrophil-to-Lymphocyte ratio (mdNLR) and Lymphocyte-to-Monocyte ratio (mdLMR) are associated with the presence of HNSCC and overall survival (OS). We used two peripheral blood DNA methylation datasets: an HNSCC case-control dataset (n = 183) and an HNSCC survival dataset (n = 407) to estimate mdSI indices. We then performed multivariate regressions to test the association between mdSI indices, HNSCC development and OS. Multivariate logistic regression revealed that elevated mdNLR was associated with increased odds of being an HNSCC case (OR = 3.25, 95% CI = 2.14-5.34, P = 4 × 10-7) while the converse was observed for mdLMR (OR = 0.88, 95% CI = 0.81-0.90, P = 2 × 10-3). In the HNSCC survival dataset, HPV16-E6 seropositive HNSCC cases had an elevated mdLMR (P = 9 × 10-5) and a lower mdNLR (P = 0.003) compared to seronegative patients. Multivariate Cox regression in the HNSCC survival dataset revealed that lower mdLMR (HR = 1.96, 95% CI = 1.30-2.95, P = 0.0013) but not lower mdNLR (HR = 0.68, 95% CI = 0.46-1.00, P = 0.0501) was associated with increased risk of death. Our results indicate that mdSI estimated by DNA methylation data is associated with the presence of HNSCC and overall survival. The mdSI indices may be used as a valuable research tool to reliably estimate SI in the absence of cell-based estimates. Rigorous validation of our findings in large prospective studies is warranted in the future.


Acute hyponatremia in the perioperative period: insights into its pathophysiology and recommendations for management.
Our purpose is to review the topic of acute postoperative hyponatremia by focusing on pertinent aspects of the physiology of water and solute excretion. Four areas will be highlighted: an examination of the source of addition of electrolyte-free water, an exploration of the basis for the very large natriuresis that occurs during cerebral salt wasting following neurosurgery, possible reasons to explain why acute postoperative hyponatremia may pose a greater risk for young women [Ayus and Arieff 1996, Ayus et al. 1992, Arieff 1986, Wijdick et al. 1991], and issues related to treatment of acute hyponatremia.


Hue memory and discrimination in young children.
As first remarked by Charles Darwin (1877), very young children frequently have difficulty when naming or choosing colors. To investigate the cause of this difficulty, we have tested preschoolers (mean age = 4.1) for hue discrimination and hue memory and compared their results with those of preadolescents (mean age = 9.6) and young adults (mean age = 25.8). The tests were designed to minimize the influence of verbal coding on the results. We find that preschoolers are as good as the two older groups in hue discrimination. However, in visual hue memory, they are significantly poorer. The 3-fold increased errors they make, relative to preadolescents and young adults, may be related to the development of visual hue categories and the integration of verbal and visual processes. However, such errors cannot explain why young children often experience extreme difficulty in color naming.


Quantifying Medication Exposure in Very Low Birth Weight Neonates.
Very low birth weight (VLBW) infants are exposed to medications with insufficient evidence describing pharmacokinetics and safety. Objective was to quantify and identify risk factors associated with the highest quartile of medication exposure. Retrospective record review of VLBW infants admitted to a level-IV neonatal intensive care unit (NICU). We obtained baseline clinical and demographic characteristics, as well as data on all medications received during admission. Characteristics of patients within the upper quartile of medication use were compared with remaining patients. Identified 106 infants, mean birth weight (BW) = 961 g, gestational age = 27.3 weeks. Infants received a median = 20 medications (range, 4-72). Those in the top quartile of medication use received ≥30 medications while in the NICU and had higher odds of being male sex, lower BW, longer length of hospital stay (LOHS), and bronchopulmonary dysplasia. Sepsis did not affect medication exposure. Antibiotics, opiates, and reflux medications were among the top prescribed. Infants are exposed to a large number of medications during NICU hospitalization, including potentially unnecessary antibiotics and reflux medications. Male sex, the presence of certain comorbidities such as necrotizing enterocolitis, and LOHS, are associated with higher exposure. Increased awareness of this issue may assist in decreasing medication exposure in VLBW populations.


Coexisting child neglect and drug abuse in young mothers: specific recommendations for treatment based on a review of the outcome literature.
Although perpetrators of child neglect often abuse illicit substances, treatment outcome evaluations in drug-abusing young mothers who have been found to neglect their children are conspicuously absent. Problem-solving interventions and family-based therapies that include skill acquisition components have demonstrated effectiveness in substance-abusing adolescents and child-neglecting mothers. The purpose of this article is (a) to review studies that have examined the relationship of drug abuse and child neglect, (b) to review clinical treatments that appear to be effective in both perpetrators of child neglect and drug-abusing adolescents, and (c) to integrate empirically validated drug abuse and child neglect interventions for use in adolescent mothers who have been found to abuse drugs and neglect their children.


Effects of Whey Protein Combined with Amylopectin/Chromium on the Muscle Protein Synthesis and mTOR Phosphorylation in Exercised Rats.
This study aimed to examine the impact of varying doses of whey protein (WP) and amylopectin/chromium complex (ACr) supplementation on muscle protein synthesis (MPS), amino acid and insulin levels, and the rapamycin (mTOR) signaling pathways in exercised rats. A total of 72 rats were randomly divided into nine groups: (1) Exercise (Ex), (2) Ex + WPI to (5) Ex + WPIV with various oral doses of whey protein (0.465, 1.55, 2.33, and 3.1 g/kg) and (6) Ex + WPI + ACr to (9) Ex + WPIV + ACr with various doses of whey protein combined with 0.155 g/kg ACr. On the day of single-dose administration, the products were given by oral gavage after exercise. To measure the protein fractional synthesis rate (FSR), a bolus dose of deuterium-labeled phenylalanine was given, and its effects were evaluated 1 h after supplementation. Rats that received 3.1 g/kg of whey protein (WP) combined with ACr exhibited the most significant increase in muscle protein synthesis (MPS) compared to the Ex group (115.7%, p < 0.0001). In comparison to rats that received the same dose of WP alone, those given the combination of WP and ACr at the same dosage showed a 14.3% increase in MPS (p < 0.0001). Furthermore, the WP (3.1 g/kg) + ACr group exhibited the highest elevation in serum insulin levels when compared to the Ex group (111.9%, p < 0.0001). Among the different groups, the WP (2.33 g/kg) + ACr group demonstrated the greatest increase in mTOR levels (224.2%, p < 0.0001). Additionally, the combination of WP (2.33 g/kg) and ACr resulted in a 169.8% increase in 4E-BP1 levels (p < 0.0001), while S6K1 levels rose by 141.2% in the WP (2.33 g/kg) + ACr group (p < 0.0001). Overall, supplementation with various doses of WP combined with ACr increased MPS and enhanced the mTOR signaling pathway compared to WP alone and the Ex group.


Modelling the compartmentalization of splicing factors.
Splicing factor (SF) compartments, also known as speckles, are heterogeneously distributed compartments within the nucleus of eukaryotic cells that are enriched in pre-mRNA SFs. We derive a fourth-order aggregation-diffusion model that describes a possible mechanism underlying the organization of SFs into speckles. The model incorporates two hypotheses, namely (1) that self-organization of dephosphorylated SFs, modulated by a phosphorylation-dephosphorylation cycle, is responsible for the formation and disappearance of speckles, and (2) that an underlying nuclear structure plays a major role in the organization of SFs. A linear stability analysis about homogeneous steady-state solutions of the model reveals how the self-interaction among dephosphorylated SFs can result in the onset of spatial patterns. A detailed bifurcation analysis of the model describes how phosphorylation and dephosphorylation modulate the onset of the compartmentalization of SFs.


In search of a theory of supercooled liquids.
Despite the absence of consensus on a theory of the transition from supercooled liquids to glasses, the experimental observations suggest that a detail-independent theory should exist.


Case report expanding the germline AXIN2- related phenotype to include olfactory neuroblastoma and gastric adenoma.
Pathogenic AXIN2 variants cause absence of permanent teeth (hypodontia), sparse hair and eye brows (ectodermal dysplasia), and gastrointestinal polyps and cancer. Inheritance is autosomal dominant with variable penetrance. Only twenty- five patients have been reported from five families. A Mayo Clinic pilot program tested 3009 newly diagnosed cancer patients for pathogenic germline variants in 83 hereditary cancer genes, including AXIN2. We found only one patient with a pathogenic AXIN2 variant. The proband was a 49 year-old female who came to Otolaryngology clinic complaining of right-sided nasal obstruction. Biopsy of identified nasal polyp revealed olfactory neuroblastoma (esthesioneuroblastoma). Surgical resection with gross, total tumor resection was followed by radiation therapy. The patient enrolled in a clinical pilot of genetic testing and a pathogenic variant in AXIN2, c.1822del (p.Leu608Phefs*81) (NM_004655.3) was found. She was seen in Medical Genetics clinic and found to have a personal history of hypodontia. Her eyebrows, hair, and nails were all normal. She underwent upper endoscopy and colonoscopy. A four mm gastric adenoma was found and removed. This is the first case reported on a patient with a pathogenic, germline AXIN2 variant and an olfactory neuroblastoma or a gastric adenoma. We propose that these could be features of the AXIN2 phenotype. The known association between gastric adenomas and familial adenomatous polyposis, the other Wnt/beta-catenin disorder, supports the hypothesis that pathogenic AXIN2 variants increase risk as well. As the odds of a chance co-occurrence of a pathogenic AXIN2 variant and an olfactory neuroblastoma are so rare, it is worth exploring potential causation. We are building a clinical registry to expand understanding of the AXIN2 phenotype and request any clinicians caring for patients with pathogenic AXIN2 variants to contact us.


Lyme disease in Italy.
We present the first cases of Lyme disease found in Italy. The diagnosis was based on clinical and laboratory data. The antigen used for indirect immunofluorescence (I.I.F.) was kindly supplied to us by Prof. R. Ackermann (Köln). Reciprocal titer was 64 in five patients, 128 in six, 256 in three and 512 in one. The patients came either from the Eastern Ligurian Coast or the Trieste Karst: these are consequently the first two Italian areas where Lyme disease has been recognized up to the present.


Virus-infected peripheral blood plasmablasts in a patient with severe fever with thrombocytopenia syndrome.
Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne viral hemorrhagic disease with a high fatality rate. It is caused by the SFTS virus and is endemic in East Asian countries such as China, South Korea, and Japan. Previous studies have shown that plasmablasts appear transiently in peripheral blood during the acute phase of SFTS, but do not specify the characteristics of these plasmablasts. In this report, we describe the features of peripheral blood plasmablasts in a patient with SFTS. Immunohistochemical and immunofluorescence staining detected a small number of atypical lymphocytes expressing the SFTS virus antigen among peripheral leukocytes in a blood sample. The phenotype of the virus-infected cells was CD27+, CD38+, MUM1+, and CD138+, which is consistent with that of plasmablasts. This novel study demonstrates that plasmablasts in the peripheral blood of patients with SFTS are targets of the SFTS virus.


Effects of ageing on carbonyl stress and antioxidant defense in RBCs of obese Type 2 diabetic patients.
In this study we investigated the effects of ageing on the carbonyl stress (protein carbonyls and 4-hydroxy-2-nonenal groups) and glutathione antioxidant defense in red blood cells (RBCs) of obese Type 2 diabetic patients with/without hypertensive complications. To this purpose the following methods were used: spectrophotometry (protein carbonyls, glutathione and glutathione peroxidase assays), immunofluorescence (4-hydroxy-2-nonenal localization), western blotting (immunodetection of carbonylated proteins). The results showed that compared to RBCs of healthy subjects, in obese Type 2 diabetics, ageing is associated with: (i) an increase in the concentration and expression of carbonylated proteins, a marker of oxidative stress; (ii) a decrease of both non-enzymatic and enzymatic endogenous glutathione defenses; (iii) a severely disturbed oxidant/antioxidant balance when obesity was associated with hypertension. The simultaneous insults of high blood pressure, obesity, and diabetes conducted to the highest carbonyl stress, exposure of 4-hydroxy-2-nonenal Michel adducts at the outer leaflet of RBCs plasmalemma, and the lowest glutathione antioxidant potential, particularly in elderly patients. These results can explain the gradual age-dependent diminishment of the detoxification potential of RBCs that at the old age can not overcome the deleterious effects of the high systemic oxidative stress.


Chondrogenesis in the synovial tissue is associated with the onset of pseudogout after total knee arthroplasty.
Postoperative pseudogout after total knee arthroplasty (TKA) is very rare, and its physical findings are very similar to infectious symptoms. In pseudogout, the mechanism underlying the deposition of calcium pyrophosphate dehydrate crystals remains unclear. Here, we report the histologic findings in a pseudogout attack in the late postoperative period after TKA. She had acute onset of arthritis of the knee 2 years after TKA. Histologic examination showed significant neutrophil infiltration. Interestingly, chondrogenesis was noted in the synovial tissue, and calcium pyrophosphate dehydrate crystals were synthesized mainly at the site of chondrogenesis, suggesting a potential mechanism underlying the occurrence of pseudogout after TKA.


A multisite randomized controlled effectiveness trial of cognitive processing therapy for military-related posttraumatic stress disorder.
Cognitive processing therapy (CPT) is currently applied in military veteran mental health services in many countries. This study tests the effectiveness of community-administered CPT for military-related PTSD under randomized controlled conditions. Fifty-nine treatment-seeking veterans with military-related PTSD were randomly allocated to receive 12 twice-weekly 60 min sessions of CPT or an equivalent period of usual treatment at veterans' community based counseling services. Intent to treat analyses found significantly greater improvement for participants receiving CPT over usual treatment at post-treatment and 3 month follow-up. CPT also produced greater improvements in anxiety, depression, social and dyadic relationships than usual treatment. No CPT related adverse events occurred during the trial. This trial reports the first randomized controlled trial evidence that CPT is an effective treatment for military PTSD and co-morbid conditions when compared to usual treatment and delivered in community settings by clinicians from diverse disciplines, preferred treatment orientation and levels of experience.


Congenital accessory mitral valve tissue anomaly in a patient with genetically confirmed hypertrophic cardiomyopathy.
Accessory mitral valve tissue is a rare congenital cardiac anomaly that was initially described in children in association with other cardiac congenital abnormalities and, more recently, has also been reported in adults. The authors report a patient with genetically confirmed hypertrophic cardiomyopathy who also had a highly mobile, free-floating membrane-like structure in contiguity with the ventricular side of the anterior mitral valve leaflet, a feature consistent with the diagnosis of accessory mitral valve tissue.


Time-course microarray transcriptome data of in vitro cultured testes and age-matched in vivo testes.
In vitro spermatogenesis, which produces fertile spermatozoa, has been successfully performed using an organ culture method from murine tissue. Here, we provide a dataset of time-course microarray transcriptome data of in vitro cultured neonate murine testes and age-matched in vivo-derived testes. The dataset presented here is related to the article titled "Transcriptome analysis reveals inadequate spermatogenesis and immediate radical immune reactions during organ culture in vitro spermatogenesis" published in Biochemical and Biophysical Research Communications in 2020 [1]. The raw data and pre-processed data are publicly available on the GEO repository (accession number GSE147982). Furthermore, the dataset provided here includes additional metadata, detailed explanations of the experiment, results of pre-processing, analysis scripts, and lists of differentially expressed genes from in vitro culture testes and in vivo testes at each time point.


Effects of two neuroleptic drugs on focal somatoparietal rhythms in free awake cats.
In freely moving cats, systemic administration of Chlorpromazine (CPZ) and Haloperidol (HP), two neuroleptics which presumably block catecholamine receptors, leads to a suppression of the waking mu-type rhythms. There is a clear difference, however, in that CPZ leads to slow wave sleep while HP only induces sustained drowsiness. The difference in their action is tentatively explained by their differential effect on an enzyme that is not involved in the metabolism of biogenic amines, tryptophan pyrrolase. We suggest that it is through this pathway that CPZ might increase and HP might decrease brain tryptophan and thereby lead to opposite changes in brain 5-HT content.


Electrical injuries, with special reference to the upper extremities. A review of 182 cases.
A twenty year experience in the management of 182 patients with electrical injuries has been reviewed. Males predominate. The average age is thirty-six years. Bodily contact with high tension wires by linemen constituted the most common accidents. High voltage injuries were sustained by 67% of patients. Burns were sustained by 74% of our cases and of these, 71% involved the upper extremities. Complications developed in three fourths of patients, and one third of patients suffered some degree of permanent disability. Mortality (2.1%) was largely due to septicemia, pneumonia, and renal failure. The wide variety of injuries necessitates individualization in treatment. Prevention offers greatest hope in management.


Prospective cohort study of psoriatic arthritis risk in patients with psoriasis in a real-world psoriasis registry.
The characteristics that predict the onset of psoriatic arthritis (PsA) among patients with psoriasis (PsO) may inform diagnosis and treatment. To develop a model to predict the 2-year risk of developing PsA among patients with PsO. This was a prospective cohort study of patients in the CorEvitas Psoriasis Registry without PsA at enrollment and with 24-month follow-up. Unregularized and regularized logistic regression models were developed and tested using descriptive variables to predict dermatologist-identified PsA at 24 months. Model performance was compared using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. A total of 1489 patients were included. Nine unique predictive models were developed and tested. The optimal model, including Psoriasis Epidemiology Screening Tool (PEST), body mass index (BMI), modified Rheumatic Disease Comorbidity Index, work status, alcohol use, and patient-reported fatigue, predicted the onset of PsA within 24 months (AUC = 68.9%, sensitivity = 82.9%, specificity = 48.8%). A parsimonious model including PEST and BMI had similar performance (AUC = 68.8%; sensitivity = 92.7%, specificity = 36.5%). PsA misclassification bias by dermatologists. PEST and BMI were important factors in predicting the development of PsA in patients with PsO over 2 years and thereby foundational for future PsA risk model development.


Maggots in the Brain: Sequelae of Ignored Scalp Wound.
A 26-year-old male had suffered a burn injury to his scalp in childhood and ignored it. He presented with a complaint of something crawling on his head. Inspection of his scalp revealed multiple maggots on the brain surface with erosion of overlying bone and scalp. He was successfully managed by surgical debridement and regular dressing.


[Specific tongue involvement revealing sarcoidosis].
Sarcoidosis is a multisystem granulomatous disease of unknown aetiology. Tongue involvement is extremely rare. Herein we report a new case. A 65-year-old woman presented with a 6-month history of painless multiple nodules on the tongue. The patient also complained of xerostomia. Besides nodules on the tongue, physical examination revealed erythematous nodules on the dorsum of the hands and feet. A diagnosis of sarcoidosis with tongue, cutaneous and salivary gland involvement was made on the basis of these findings and further investigations performed. The patient's condition showed improvement with partial regression of tongue lesions after oral steroid therapy. Tongue involvement in sarcoidosis is exceedingly rare. It may be isolated or part of a generalized multisystem sarcoidosis. Nodules, indurations and swelling are the most common clinical manifestations. Management of tongue sarcoidosis is not consensual. Oral corticosteroids appear to be the most effective therapy. Sarcoidosis of the tongue should be considered when chronic unexplained nodules are noted. Diagnosis can easily be confirmed by a histological examination of mucosal biopsy.


Comparative effectiveness of repeated ketamine infusions in treating anhedonia in bipolar and unipolar depression.
Anhedonia is a common, persistent, and disabling phenomenon in patients with major depressive disorder (MDD) and bipolar depression (BD). This study was conducted to investigate the comparative effectiveness of repeated ketamine infusions in treating anhedonia in Chinese individuals suffering from MDD and BD. Ninety-seven individuals suffering from MDD (n = 77) or BD (n = 20) were treated with six intravenous infusions of ketamine (0.5 mg/kg) administered over 40 min. Anhedonia was measured through the Montgomery-Åsberg Depression Rating Scale (MADRS). The antianhedonic response and remission were defined as ≥ 50% and ≥ 75% reduction in MADRS anhedonia subscale score one day after the sixth infusion, respectively. Anti-anhedonic response and remission rates after the sixth ketamine infusion were 48.5% (95% confidence interval = 38.3%-58.6%) and 30.9% (95% confidence interval = 21.6%-40.3%), respectively. When compared to baseline, a significant reduction in the MADRS anhedonia subscale score was observed at 4 h after the first infusion and was maintained with repeated infusions at any time point (all Ps < 0.05). The anti-anhedonic effect of ketamine did not differ between the MDD and BD groups. This preliminary study found that repeated ketamine infusions appeared to be effective at rapidly ameliorating anhedonia, with similar efficacy in MDD and BD.


Drugs Affecting Lipid Metabolism--XIII International Symposium. 30 May-3 June 1998, Florence, Italy.
This meeting convened over four days in the historical city of Florence, Italy. It attracted around 2500 attendees mainly from academia and pharmaceutical companies but also included clinical cardiologists from around the world. The conference covered a wide range of topics in the field of heart disease and lipid lowering drugs in the plenary sessions, workshops, and over 300 posters. The plenary sessions and series of workshops entitled "Drugs affecting lipid metabolism" were well attended and stimulated much discussion. There was a noticeably high content of basic research in the workshops, particularly in the field of molecular biology, although clinical studies also made up a large part of the data.


Chitosan sponges for local synergistic infection therapy: a pilot study.
Although bacterial antibiotic resistance is increasing, fewer new antibiotics are being developed to compensate. Localized delivery of synergistic antiseptics and antibiotics with a chitosan sponge device may offer an alternative infection treatment. In this pilot study, we asked whether antiseptic and antibiotic combinations provided in vitro synergism against Staphylococcus aureus, whether synergism reduces cell viability, and whether their combination releases drugs at inhibitory levels. To investigate the pharmacodynamics among three combinations of the antiseptic chlorhexidine digluconate (CHX) with the antibiotics amikacin, daptomycin, and vancomycin (VAN) (n=1), we determined the fractional inhibitory concentration (FIC) index against S aureus Cowan I. The determined synergistic combination of CHX and VAN was evaluated for cell compatibility using NIH/3T3 fibroblasts (n=3) and the drug release profile from a chitosan sponge device (n=5). With an FIC index<0.5, the combination of CHX+VAN exhibited synergism against S aureus. CHX concentrations≥3.91 μg/mL resulted in fibroblast viability decrease, whereas the combination of CHX+VAN did not decrease fibroblast viability until their concentrations reached ≥7.81 μg/mL. The CHX and VAN release profile, both individually and in combination, was an initial bolus with no difference between eluate concentrations after Day 5. CHX+VAN combination may be delivered locally by a chitosan sponge that synergistically inhibits S aureus growth. The use of synergism between combined antibiotic and antiseptics delivered at high local concentrations with an implanted chitosan sponge may provide a useful alternative infection treatment option.


Lack of toxicity of hydroethanolic extract from Mitragyna inermis (Willd.) O. Kuntze by gavage in the rat.
In traditional medicine in Mali, extracts derived from Mitragyna inermis (Willd.) O. Kuntze (Family: Rubiaceae) are commonly used to treat malaria. The antimalarial activity and the lack of genotoxicity in vitro and in vivo have been demonstrated in previous studies. Acute and chronic evaluation of the toxicity of the hydroethanolic extract of Mitragyna inermis leaves was performed in this study, according to the recommendations (cahier de l'Agence no. 3) of the French Drug Office. Two dosages (300 mg/kg and 3 g/kg) were given in one single administration by gavage to male and female rats. No animal died and no behavioral signs of acute toxicity were observed. Chronic toxicity studies over 28 days showed no changes in body weight and no macroscopic abnormality in the 14 organs examined after the animals were sacrificed. With the 3 g/kg/d drug dosage (100-fold higher than those proposed in man), only slight histological abnormalities were observed. Statistically significant differences, compared to control animals, in the weight of some organs and the values of some haematological or biochemical parameters were observed. However, these values always remained in the range given by the breeder for naive animals of the same strain. These investigations thus seemed to indicate the safety of repeated oral administration (up to 3 g/kg/d) of the hydroethanolic extract of Mitragyna inermis leaves, which can therefore be continuously used with safety by the African population in traditional treatment of malaria.


Looking to Europe: something's changed in Italy.
The new Italian law regulating the use of assisted reproduction technologies (ARTs) prohibits treatment widely practiced in Europe. The new regulations have already given rise to a humiliating form of "reproductive tourism" of Italian subfertile couples.


Long-term survival curve of methicillin-resistant Staphylococcus aureus on clinical contact surfaces in natural-like conditions.
We investigated methicillin-resistant Staphylococcus aureus (MRSA) survival on a noncritical environmental surface in real-life conditions (dental chair located in a box of a Dentistry Department, subjected to microclimate variations and presence of people) and with a plausible baseline inoculum (5-log colony-forming units) in contrast to survival that has been frequently tested in laboratory conditions and/or using high baseline levels. We tested 5 freshly isolated sporadic strains and observed a drastic MRSA fall (>90%) 15 minutes after exposure to the environment. After 4 months, we detected MRSA at very low levels in 9 out of 25 tests. The MRSA survival curve showed that the velocity of log count decrease, highest soon after exposure, tended to decrease progressively. Thus, whereas the risk for infection through shared surfaces is probably minimal, the risk for MRSA diffusion in the community is high.


Drivers and Risk Factors of Unplanned 30-Day Readmission Following Spinal Cord Stimulator Implantation.
Unplanned 30-day readmission rates contribute significantly to growing national healthcare expenditures. Drivers of unplanned 30-day readmission after spinal cord stimulator (SCS) implantation are relatively unknown. The aim of this study was to determine drivers of 30-day unplanned readmission following SCS implantation. The National Readmission Database was queried to identify all patients who underwent SCS implantation for the 2013 calendar year. Patients were grouped by readmission status, "No Readmission" and "Unplanned 30-day Readmission." Patient demographics and comorbidities were collected for each patient. The primary outcome of interest was the rate of unplanned 30-day readmissions and associated driving factors. A multivariate analysis was used to determine independent predictors of unplanned 30-day readmission after SCS implantation. We identified 1521 patients who underwent SCS implantation, with 113 (7.4%) experiencing an unplanned readmission within 30 days. Baseline patient demographics, comorbidities, and hospital characteristics were similar between both cohorts. The three main drivers for 30-day readmission after SCS implantation include: 1) infection (not related to SCS device), 2) infection due to device (limited to only hardware infection), and 3) mechanical complication of SCS device. Furthermore, obesity was found to be an independent predictor of 30-day readmission (OR: 1.86, p = 0.008). Our study suggests that infectious and mechanical complications are the primary drivers of unplanned 30-day readmission after SCS implantation, with obesity as an independent predictor of unplanned readmission. Given the technological advancements in SCS, repeated studies are necessary to identify factors associated with unplanned 30-day readmission rates after SCS implantation to improve patient outcomes and reduce associated costs.


Sinomenine inhibits macrophage M1 polarization by downregulating α7nAChR via a feedback pathway of α7nAChR/ERK/Egr-1.
Sinomenine (SIN) is an anti-inflammatory drug that has been used for decades in China to treat arthritis. In a previous study, SIN acted on α7 nicotinic acetylcholine receptor (α7nAChR) to inhibit inflammatory responses in macrophages, which indicates a new anti-inflammatory mechanism of SIN. However, the level of α7nAChR was increased in the inflammatory responses and was downregulated by SIN in vitro, so the underlying mechanisms of SIN acting on α7nAChR remain unclear. To analyze the role of α7nAChR in inflammation and the effect and mechanism of SIN regulation of α7nAChR. The effects of SIN on α7nAChR in endotoxemic mice and LPS-stimulated macrophages were observed. Nicotine (Nic) was used as a positive control, and berberine (Ber) was used as a negative control targeting α7nAChR. The antagonists of α7nAChR, α-bungarotoxin (BTX) and mecamylamine (Me), were used to block α7nAChR. In RAW264.7 macrophage cells in vitro, α7nAChR short hairpin RNA (shRNA) was used to knock down α7nAChR. Macrophage polarization was analyzed by the detection of TNF-α, IL-6, iNOS, IL-10, Arg-1, and Fizz1. U0126 was used to block ERK phosphorylation. The cytokines α7nAChR, ERK1/2, p-ERK1/2 and Egr-1 were detected. SIN decreased the levels of TNF-α, IL-6 and the expression of α7nAChR increased by LPS in endotoxemic mice. The above effects of SIN were attenuated by BTX. In the α7nAChR shRNA transfected RAW264.7 cells, compared with the control, α7nAChR was knocked down, and M1 phenotype markers (including TNF-α, IL-6, and iNOS) were significantly downregulated, whereas M2 phenotype markers (including IL-10, Arg-1, and Fizz1) were significantly upregulated when stimulated by LPS. SIN inhibited the expression of p-ERK1/2 and the transcription factor Egr-1 induced by LPS in RAW264.7 cells, and the above effects of SIN were attenuated by BTX. The expression of α7nAChR was suppressed by U0126, which lessened the expression of p-ERK1/2 and Egr-1. SIN acts on α7nAChR to inhibit inflammatory responses and downregulates high expression of α7nAChR in vivo and in vitro. The increase of α7nAChR expression is correlated with inflammatory responses and participates in macrophage M1 polarization. SIN downregulates α7nAChR via a feedback pathway of α7nAChR/ERK/Egr-1, which contributes to inhibiting macrophage M1 polarization and inflammatory responses.


A new species of genus Phonarellus Gorochov, 1983 from Yunnan, China (Orthoptera: Gryllidae: Gryllinae).
Phonarellus Gorochov, 1983 is comprised of 11 extant species. We describe a new species, Phonarellus (Phonarellus) zebripes He sp. nov. from Yunnan province, China. It is different from other Phonarellus species in possessing black and white stripes on the hind femora. The type specimens are deposited in Museum of Biology, East China Normal University (ECNU).


Identification of transcription factor co-regulators that drive prostate cancer progression.
In prostate cancer (PCa), and many other hormone-dependent cancers, there is clear evidence for distorted transcriptional control as disease driver mechanisms. Defining which transcription factor (TF) and coregulators are altered and combine to become oncogenic drivers remains a challenge, in part because of the multitude of TFs and coregulators and the diverse genomic space on which they function. The current study was undertaken to identify which TFs and coregulators are commonly altered in PCa. We generated unique lists of TFs (n = 2662), coactivators (COA; n = 766); corepressors (COR; n = 599); mixed function coregulators (MIXED; n = 511), and to address the challenge of defining how these genes are altered we tested how expression, copy number alterations and mutation status varied across seven prostate cancer (PCa) cohorts (three of localized and four advanced disease). Testing of significant changes was undertaken by bootstrapping approaches and the most significant changes were identified. For one commonly and significantly altered gene were stably knocked-down expression and undertook cell biology experiments and RNA-Seq to identify differentially altered gene networks and their association with PCa progression risks. COAS, CORS, MIXED and TFs all displayed significant down-regulated expression (q.value < 0.1) and correlated with protein expression (r 0.4-0.55). In localized PCa, stringent expression filtering identified commonly altered TFs and coregulator genes, including well-established (e.g. ERG) and underexplored (e.g. PPARGC1A, encodes PGC1α). Reduced PPARGC1A expression significantly associated with worse disease-free survival in two cohorts of localized PCa. Stable PGC1α knockdown in LNCaP cells increased growth rates and invasiveness and RNA-Seq revealed a profound basal impact on gene expression (~ 2300 genes; FDR < 0.05, logFC > 1.5), but only modestly impacted PPARγ responses. GSEA analyses of the PGC1α transcriptome revealed that it significantly altered the AR-dependent transcriptome, and was enriched for epigenetic modifiers. PGC1α-dependent genes were overlapped with PGC1α-ChIP-Seq genes and significantly associated in TCGA with higher grade tumors and worse disease-free survival. These methods and data demonstrate an approach to identify cancer-driver coregulators in cancer, and that PGC1α expression is clinically significant yet underexplored coregulator in aggressive early stage PCa.


Considerations in reference values for nerve conduction studies.
Despite the universal application of reference values, understanding their production and underlying limitations is often overlooked. Without a deeper consideration for this issue, opportunities for treatment may be missed or misdiagnosis may occur. This article reviews relevant biostatistical issues in the generation of reference intervals and subsequent errors that may occur. Further discussion includes recommendations on how to correct statistical errors, as well as more recent methods for distinguishing between "healthy" and "diseased."


Changes in bone biomarkers in response to different dosing regimens of cholecalciferol supplementation in children with chronic kidney disease.
The effect of different dosing regimens of cholecalciferol supplementation on bone biomarkers has not been studied in children with chronic kidney disease (CKD). This is a post hoc analysis of a multi-center randomized controlled trial which included children with CKD stages 2-4 with vitamin D deficiency (25-hydroxy vitamin D (25OHD) < 30 ng/ml) randomized 1:1:1 to receive an equivalent dose of oral cholecalciferol as daily, weekly or monthly treatment. Markers of bone formation (bone alkaline phosphatase (BAP), procollagen I N terminal peptide (PINP)), bone resorption (tartarate-resistant acid phosphatase 5b (TRAP), C terminal telopeptide (CTX)), and osteocyte markers (intact fibroblast growth factor 23 (iFGF23), sclerostin) and soluble klotho were measured at baseline and after 3 months of intensive replacement therapy. The change in biomarkers and ratio of markers of bone formation to resorption were compared between treatment arms. BAP and TRAP were expressed as age- and sex-specific z-scores. 25OHD levels increased with cholecalciferol supplementation, with 85% achieving normal levels. There was a significant increase in the BAP/TRAP ratio (p = 0.04), iFGF23 (p = 0.004), and klotho (p = 0.002) with cholecalciferol therapy, but this was comparable across all three therapy arms. The BAPz was significantly higher in the weekly arm (p = 0.01). The change in 25OHD (Δ25OHD) inversely correlated with ΔPTH (r = - 0.4, p < 0.001). Although cholecalciferol supplementation was associated with a significant increase in bone formation, the three dosing regimens of cholecalciferol supplementation have a comparable effect on the bone biomarker profile, suggesting that they can be used interchangeably to suit the patient's needs and optimize adherence to therapy. A higher resolution version of the Graphical abstract is available as Supplementary information.


miR-874 suppresses the proliferation and metastasis of osteosarcoma by targeting E2F3.
Increasing evidence indicates that microRNAs (miRNAs) play critical roles in osteosarcoma (OS) occurrence and development. MicroRNA-874 (miR-874) has proven to be dysregulated in several human cancers. However, the biological function and underlying molecular mechanism of miR-874 in OS remain unclear. In this study, we aimed to investigate the biological role and potential mechanism of miR-874 in OS. Here, we found that miR-874 expression was significantly decreased in OS cell lines and tissues by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), and its expression was correlated with tumor-node-metastasis (TNM) stage, tumor size, and lymph node metastasis (all P < 0.01). Functional study revealed that overexpression of miR-874 in OS cells could remarkably inhibit proliferation, migration, and invasion and induce cell apoptosis. In addition, E2F transcription factor 3 (E2F3) was confirmed as a target of miR-874 in OS cells. E2F3 mRNA expression was upregulated and was inversely correlated with the level of miR-874 in OS tissues. Importantly, downregulation of E2F3 mimicked the effect of overexpression miR-874 in OS cells, and E2F3 overexpression partially attenuated the tumor-suppressive effects of miR-874 in OS cells. Taken together, these findings suggested that miR-874 might suppress the growth and metastasis of OS cells partially by targeting E2F3.


IL-3 stimulated haemopoietic stem cell proliferation: evidence for G protein independent mitogenic signalling events.
Interleukin-3 stimulates the survival and proliferation of the FDCP-Mix 1 multipotent stem cell line. We have investigated the possible involvement of a guanyl nucleotide regulatory (G) protein(s) in the IL-3 stimulated proliferative response. We report here that pertussis toxin (PT) can partially inhibit IL-3 stimulated DNA synthesis and that this inhibition is bypassed by TPA. The ADP-ribosylation of the PT substrate G protein in vivo is complete in 2 hours without concomitant inhibition of IL-3 stimulated hexose transport or Na+/H+ exchange. When loaded into FDCP-Mix 1 cells fluoroaluminate and GTP-gamma-S, which can directly activate G proteins, are not capable of mimicking the effects of IL-3. Evidence is also presented that IL-3 does not stimulate a membrane-bound high affinity GTPase activity in the FDCP-Mix 1 cell line. These data suggest that a PT substrate G protein(s) can influence the IL-3 signalling cascade in an indirect or permissive manner, but that the IL-3 receptor does not directly couple to a PT substrate G protein.


Cortical gene expression in the vitamin E-deficient rat: possible mechanisms for the electrophysiological abnormalities of visual and neural function.
In mammals, severe and chronic deficiency of vitamin E (alpha-tocopherol) is associated with a characteristic neurological syndrome. Previously, we have shown that this syndrome is accompanied by electrophysiological abnormalities of neural and visual function. To investigate the molecular basis of the observed abnormalities, we used microarrays to monitor the expression of approximately 14,000 genes in the cerebral cortex from rats which had received diets containing 0, 1.25 and 5.0 mg/kg diet of all-rac-alpha-tocopheryl acetate for 14 months. Compared to the groups receiving 1.25 and 5.0 mg/kg alpha-tocopheryl acetate, a total of 11 genes were statistically significantly upregulated (> or =1.3-fold) and 34 downregulated (< or =1.3-fold) in the vitamin E-deficient group. Increased expression was observed for the genes encoding the antioxidant enzyme catalase and the axon guidance molecule tenascin-R, while decreased expression was detected for genes encoding protein components of myelin and determinants of neuronal signal propagation. Thus our observations suggest that vitamin E deficiency results in transcriptional alterations in the cerebral cortex of the rat which are consistent with the observed neurological and electrophysiological alterations.


Environmentally-friendly oxygen-free roasting/wet magnetic separation technology for in situ recycling cobalt, lithium carbonate and graphite from spent LiCoO2/graphite lithium batteries.
The definite aim of the present paper is to present some novel methods that use oxygen-free roasting and wet magnetic separation to in situ recycle of cobalt, Lithium Carbonate and Graphite from mixed electrode materials. The in situ recycling means to change waste into resources by its own components, which is an idea of "waste+waste→resources." After mechanical scraping the mixed electrode materials enrich powders of LiCoO2 and graphite. The possible reaction between LiCoO2 and graphite was obtained by thermodynamic analysis. The feasibility of the reaction at high temperature was studied with the simultaneous thermogravimetry analysis under standard atmospheric pressure. Then the oxygen-free roasting/wet magnetic separation method was used to transfer the low added value mixed electrode materials to high added value products. The results indicated that, through the serious technologies of oxygen-free roasting and wet magnetic separation, mixture materials consist with LiCoO2 and graphite powders are transferred to the individual products of cobalt, Lithium Carbonate and Graphite. Because there is not any chemical solution added in the process, the cost of treating secondary pollution can be saved. This study provides a theoretical basis for industrial-scale recycling resources from spent LIBs.


Intradermally administered TLR4 agonist GLA-SE enhances the capacity of human skin DCs to activate T cells and promotes emigration of Langerhans cells.
The natural TLR4 agonist lipopolysaccharide (LPS) has notable adjuvant activity. However, it is not useful as a vaccine adjuvant due to its toxicity. Glucopyranosyl lipid A (GLA) is a synthetic derivative of the lipid A tail of LPS with limited cytotoxicity, but strong potential to induce immune responses in mice, guinea pigs, non-human primates, and humans. In this study we determined how this synthetic TLR4 agonist affects the function of different subsets of human skin dendritic cells (DCs). The effect of GLA in an aqueous formulation (GLA-AF) or in an oil-in-water emulsion (GLA-SE) was compared to that of LPS and TLR3 agonist poly(I:C) using a human skin explant model with intradermal injections for the administration of the agonists. Intradermal injection of GLA-SE or LPS, but not GLA-AF, enhanced the emigration of CD1a(high)/langerin(+) Langerhans cells (LCs), but not dermal DCs (DDCs). LCs and CD14(-) DDCs exhibited an enhanced mature phenotype following intradermal administration of either of the two GLA formulations tested, similar to DCs that emigrated from LPS-injected skin. However, only injection of GLA-SE resulted in a significant increase in the production of the wide range of cytokines that is observed with LPS. Moreover, DCs that emigrated from GLA-SE-injected skin induced stronger CD4(+) T-cell activation, as indicated by a more pronounced T-cell proliferation, than DCs from skin injected with GLA-AF or LPS. Altogether, our data show that GLA-SE has a notable potency to stimulate the function of skin DCs, indicating that GLA-SE may be a good candidate as adjuvant for vaccines administered via the intradermal route.


Beta-glucuronidase and hyperbilirubinemia in breast-Fed babies.
In the present study we analyzed breast milk samples from mothers of breast-fed, healthy, term babies with unexplained prolonged jaundice for beta-glucuronidase activity. The differences of enzyme activity were not statistically significant in comparison to a control group of nonjaundiced newborns. We conclude that beta-glucuronidase is not the only cause of prolonged jaundice in neonates.


catena-Poly[[(benzyl-diphenyl-phosphine-κP)silver(I)]-μ-nitrato-κ2 O:O'-[(benzyl-diphenyl-phosphine-κP)silver(I)]-μ-nitrato-κ4 O,O':O',O''].
The structure of the title complex, [Ag2(NO3)2(C19H17P)2] n , reveals a chain emanating from the coordination of one phosphine ligand to each silver(I) cation, as well as the bis-monodentate coordination of a bridging nitrato ligand (per Ag atom) and the bis-bidentate coordination of another bridging nitrato ligand (per Ag atom). The distorted four-coordinate Ag atoms are characterized by bonding angles that notably deviate from the ideal tetra-hedral shape.


Sentiment Analysis of Comments of American Birders during Two Waves of the COVID-19 Pandemic Reveal More Negative Sentiments in the Context of Birding.
Human-nature relationships are an important aspect of leisure research. Previous studies also reported that nature-related activities have a health benefit. In this study, we surveyed US-American birdwatchers at two time points during the COVID pandemic (independent samples). During the beginning of the COVID pandemic in spring 2020, we analyzed their comments with an AI sentiment analysis. Approximately one year later (winter 2020/21), during the second wave, the study was repeated, and a second data set was analyzed. Here we show that during the ongoing pandemic, the sentiments became more negative. This is an important result because it shows that despite the positive impact of nature on mental health, the sentiments become more negative in the enduring pandemic.


Comparative prognostic value of automatic quantitative analysis versus semiquantitative visual analysis of exercise myocardial perfusion single-photon emission computed tomography.
The purpose of this study was to determine the prognostic value of automatic quantitative analysis in exercise dual-isotope myocardial perfusion single-photon emission computed tomography (SPECT) and to compare the prognostic value of quantitative analysis to semiquantitative visual SPECT analysis. Extent, severity and reversibility of exercise myocardial perfusion defects have been shown to correlate with prognosis. However, most studies examining the prognostic value of SPECT in chronic coronary artery disease (CAD) have been based on visual analysis by experts. We studied 1,043 consecutive patients with known or suspected CAD who underwent rest Tl-201/exercise Tc-99m sestamibi dual-isotope myocardial perfusion SPECT and were followed up for at least 1 year (mean 20.0+/-3.7 months). After censoring 59 patients with early coronary artery bypass grafting or percutaneous transluminal coronary angioplasty, <60 days after nuclear testing, the final population consisted of 984 patients (36% women, mean age 63+/-12 years). During the follow-up period, 28 hard events (14 cardiac deaths, 14 nonfatal myocardial infarctions) occurred. Patients with higher defect extent (>10%), severity (>150) and reversibility (>5%) by quantitative SPECT defect analysis, as well as those with an abnormal scan (>2 abnormal segments, summed stress score >4 and summed difference score >2) by semiquantitative visual SPECT analysis, had a significantly higher hard event rate compared to patients with a normal scan (p < 0.001). With both visual and quantitative analyses, hard event rates of approximately 1% with normal scans and 5% with abnormal scans (p > 0.05) were observed over the 20-month follow-up period. A Cox proportional hazards regression model showed that chi-square increased similarly with the addition of quantitative defect extent and visual summed stress score variables after considering both clinical and exercise variables (improvement chi-square = 11 for both, p < 0.0007). There were no significant differences in the areas under receiver operating characteristic curves between quantitative and visual analysis (p > 0.70). Linear regression analysis also indicated that quantitative assessments correlated well with visual semiquantitative assessments. The findings of this study indicate that automatic quantitative analysis of exercise stress myocardial perfusion SPECT is similar to semiquantitative expert visual analysis for prognostic stratification. These findings may be of particular clinical importance in laboratories with less experienced visual interpreters.


Impact of FLT3 mutations and promyelocytic leukaemia-breakpoint on clinical characteristics and prognosis in acute promyelocytic leukaemia.
In the present study 170 newly diagnosed acute promyelocytic leukaemia patients (M3: n = 121; M3v: n = 49) were molecularly characterised with respect to PML breakpoint and additional molecular mutations. In total, 83 patients were positive for bcr1 (49%), five for bcr2 (3%) and 82 for bcr3 (48%). Bcr3 was more frequent in M3v (65.3%) compared with M3 (41.3%) (P = 0.005). Cases with bcr3 showed a significantly higher white blood cell count (median: 3.65 x 10(9)/l vs. 1.59 x 10(9)/l, P = 0.003), as well as a higher PML-RARAABL expression ratio (14.8% vs. 72.7%, P < 0.005) compared with bcr1. FLT3-length-mutations were detected more frequently together with bcr3 compared with bcr1 (56.5% vs. 19.4%, P < 0.001) and in M3v compared with M3 (64.5% vs. 24.1%, P < 0.005). FLT3 tyrosine kinase mutations were found in eight cases (6.4%) and were distributed equally within the total group. Analysis for further mutations revealed no MLL-PTD and KIT mutations and only two cases of 99 analysed (2%) with NRAS mutations. FLT3-mutations were detected in 62 of 139 cases (44.6%) and associated with a significant lower overall survival (P = 0.0339). In addition, cases with bcr3 showed a tendency for a worse event-free survival (P = 0.0795) compared with the bcr1 group.


A tessellated lymphoid network provides whole-body T cell surveillance in zebrafish.
Homeostatic trafficking to lymph nodes allows T cells to efficiently survey the host for cognate antigen. Nonmammalian jawed vertebrates lack lymph nodes but maintain diverse T cell pools. Here, we exploit in vivo imaging of transparent zebrafish to investigate how T cells organize and survey for antigen in an animal devoid of lymph nodes. We find that naïve-like T cells in zebrafish organize into a previously undescribed whole-body lymphoid network that supports streaming migration and coordinated trafficking through the host. This network has the cellular hallmarks of a mammalian lymph node, including naïve T cells and CCR7-ligand expressing nonhematopoietic cells, and facilitates rapid collective migration. During infection, T cells transition to a random walk that supports antigen-presenting cell interactions and subsequent activation. Our results reveal that T cells can toggle between collective migration and individual random walks to prioritize either large-scale trafficking or antigen search in situ. This lymphoid network thus facilitates whole-body T cell trafficking and antigen surveillance in the absence of a lymph node system.


Anaphylactic shock due to cow's milk protein hypersensitivity in a breast-fed infant.
A newborn infant developed anaphylactic shock three times, once after ingesting his mother's milk and once after ingesting a formula containing casein hydrolysate. Symptoms resolved after cow's milk was withdrawn from the mother's diet and lactation was resumed. The case demonstrates that anaphylactic shock may occur in breast-fed infants and emphasizes the need to consider allergic phenomena even in these infants.


Arachidonic acid-induced dilation in human coronary arterioles: convergence of signaling mechanisms on endothelial TRPV4-mediated Ca2+ entry.
Arachidonic acid (AA) and/or its enzymatic metabolites are important lipid mediators contributing to endothelium-derived hyperpolarizing factor (EDHF)-mediated dilation in multiple vascular beds, including human coronary arterioles (HCAs). However, the mechanisms of action of these lipid mediators in endothelial cells (ECs) remain incompletely defined. In this study, we investigated the role of the transient receptor potential vanilloid 4 (TRPV4) channel in AA-induced endothelial Ca(2+) response and dilation of HCAs. AA induced concentration-dependent dilation in isolated HCAs. The dilation was largely abolished by the TRPV4 antagonist RN-1734 and by inhibition of endothelial Ca(2+)-activated K(+) channels. In native and TRPV4-overexpressing human coronary artery ECs (HCAECs), AA increased intracellular Ca(2+) concentration ([Ca(2+)]i), which was mediated by TRPV4-dependent Ca(2+) entry. The AA-induced [Ca(2+)]i increase was inhibited by cytochrome P450 (CYP) inhibitors. Surprisingly, the CYP metabolites of AA, epoxyeicosatrienoic acids (EETs), were much less potent activators of TRPV4, and CYP inhibitors did not affect EET production in HCAECs. Apart from its effect on [Ca(2+)]i, AA induced endothelial hyperpolarization, and this effect was required for Ca(2+) entry through TRPV4. AA-induced and TRPV4-mediated Ca(2+) entry was also inhibited by the protein kinase A inhibitor PKI. TRPV4 exhibited a basal level of phosphorylation, which was inhibited by PKI. Patch-clamp studies indicated that AA activated TRPV4 single-channel currents in cell-attached and inside-out patches of HCAECs. AA dilates HCAs through a novel mechanism involving endothelial TRPV4 channel-dependent Ca(2+) entry that requires endothelial hyperpolarization, PKA-mediated basal phosphorylation of TRPV4, and direct activation of TRPV4 channels by AA.


Ossification of the Posterior Longitudinal Ligament: Etiology, Diagnosis, and Outcomes of Nonoperative and Operative Management.
Study Design Narrative review. Objective To provide an overview on the diagnosis, natural history, and nonoperative and operative management of ossification of the posterior longitudinal ligament (OPLL). OPLL is a multifactorial condition caused by ectopic hyperostosis and calcification of the posterior longitudinal ligament. Familial inheritance and genetic factors have been implicated in the etiology of OPLL. The cervical spine is most commonly affected followed by the thoracic spine. The clinical manifestations range from asymptomatic to myelopathy or myeloradiculopathy. Methods Using PubMed, studies published prior to October 2014 with the keywords "OPLL, etiology"; "OPLL, genetics"; "OPLL, spinal cord injury"; "OPLL, natural history"; "OPLL, non-surgical management"; OPLL, surgical management"; "OPLL, surgical complications" were evaluated. Results The review addresses the etiology, epidemiology, classification, clinical presentation, imaging findings, and nonoperative and operative management of OPLL. Complications associated with surgical management of OPLL are also discussed. Conclusions OPLL commonly presents with myelopathy and radiculopathy. Spine providers should consider OPLL in their differential diagnosis and when reviewing images. If surgical intervention is pursued, imaging-based measurements and findings can help in choosing an anterior versus posterior surgical approach.


Computational and experimental research on mechanism of cis/trans isomerization of oleic acid.
The harm of trans-fatty acids to health has aroused public concern. It is believed that the main source of trans-fatty acids in diets is the isomerization of unsaturated fatty acids in edible oils during cooking. However, the information on the isomerization mechanism is very limited. In this paper, we used oleic acid, an unsaturated fatty acid, as a simplified model for edible oil and investigated the mechanism of cis/trans isomerization by computation and experiments. The computational results show that Rc-O-O-H is a very important intermediate, and the cleavage of O-O bond in Rc-O-O-H is the rate-controlling step during the cis/trans isomerization. Using the ATR-FTIR measurements, the contents of elaidic acid were measured quantitatively in sites. The experimental results indicate that the cis/trans isomerization of oleic acid can occur obviously only under oxidizing condition when the temperature is higher than 120 °C.


Surgical androgen deprivation therapy in advanced prostate cancer in patients of African descent: comparison of biochemical efficacy of bilateral total and subcapsular orchidectomy.
Surgical androgen deprivation therapy (ADT) to treat advanced prostate cancer can be achieved either by bilateral total orchidectomy (BTO) or bilateral subcapsular orchidectomy (BSCO). However, biochemical and clinical equivalence between BTO and BSCO among native Africans is undocumented. To compare the biochemical response (testosterone and prostate specific antigen) in patients who had BTO and BSCO for advanced prostate cancer. A randomized single- blind study of 64 consenting patients that underwent either BTO or BSCO. Pre- and post-operative PSA and testosterone assays were done serially at intervals and compared between each treatment group. Each treatment group were similar with no statistically significant difference in terms of age (p= 0.449) or degree of tumor differentiation (p =0.714). Neither median testosterone (p= 0.515) nor the mean pre-operative PSA differ between the two groups (p = 0.482). Also, similar trends were noticed post operatively except at the 2nd month when a statistically significant difference was recorded (p = 0.003). The two techniques of orchidectomy were effective in accomplishing androgen deprivation. They produced similar biochemical (testosterone and PSA) response.


MolFind2: A Protocol for Acquiring and Integrating MS3 Data to Improve In Silico Chemical Structure Elucidation for Metabolomics.
Structure elucidation of metabolites (<1000 Da) in biofluids is extremely challenging due to the diversity and complexity of chemical structure space. Generally, due to lack of reference tandem mass data (MS2), in silico fragmenters are used to rank candidates acquired from chemical databases as a function on how well they explain an experimental collision-induced dissociation spectrum. However, multistage fragmentation data (i.e., MS3) have not been adequately utilized in current metabolomics structure elucidation pipelines. To address this shortcoming, here we describe an experimental (nontargeted direct infusion ion mobility-mass spectrometry-based) and computational workflow to acquire and utilize multistage mass (MS3) spectrometry data for database-assisted structure elucidation.


Impact of a transitions of care pilot service established by pharmacy residents within an academic medical center.
The impact of a pharmacy postgraduate year (PGY)-2 resident-led transitions of care (TOC) pilot service targeting patients with chronic obstructive pulmonary disorder (COPD) and heart failure (HF) was evaluated in terms of 30-day hospital readmissions (primary objective) at the University of Louisville Hospital (ULH) and 30-day emergency department (ED) visits at ULH (secondary objective). The study was conducted at an urban academic teaching hospital. Before this pilot service, there were no formal TOC services for patients at high risk for readmission to ULH. The TOC pilot service providing coverage 16 h/week included patients aged at least 18 years admitted to the ULH internal medicine team with a primary or secondary diagnosis of COPD or HF. Patients to be discharged to a location other than home or who could not be contacted after discharge were excluded. The service consisted of pharmacist-patient interactions before discharge; within 72 hours after discharge, over the telephone; and 7-14 days after discharge, in person. Data were collected by retrospective chart review from patients enrolled between November 2017 and October 2018. For comparison, a computer-generated report identified patients who met the criteria for the pilot service but could not be enrolled. Of the 23 patients enrolled in the TOC pilot service, none required readmission to ULH within 30 days, compared with 12.3% of all other eligible patients. Similarly, no patients enrolled in the TOC pilot service presented to the ED within 30 days after discharge, compared with 18.6% of the comparator group. Completion rates of postdischarge follow-up were 65.2% for the telephone call and 52.2% for the clinic visit. PGY-2 ambulatory care pharmacy residents implemented a new TOC service that contributed to lower rates of 30-day readmissions and ED visits than those for other eligible patients.


Human evolution: sex-specific contributions to genome variation.
Studies of maternally-inherited mitochondrial DNA have provided evidence that all modern humans have a common, 200,000 year old African ancestor. Recent studies of Y chromosome variation support this view and suggest that males and females have contributed differentially to human genome variation.


Traditional Chinese Nootropic Medicine Radix Polygalae and Its Active Constituent Onjisaponin B Reduce β-Amyloid Production and Improve Cognitive Impairments.
Decline of cognitive function is the hallmark of Alzheimer's disease (AD), regardless of the pathological mechanism. Traditional Chinese medicine has been used to combat cognitive impairments and has been shown to improve learning and memory. Radix Polygalae (RAPO) is a typical and widely used herbal medicine. In this study, we aimed to follow the β-amyloid (Aβ) reduction activity to identify active constituent(s) of RAPO. We found that Onjisaponin B of RAPO functioned as RAPO to suppress Aβ production without direct inhibition of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) and γ-secretase activities. Our mechanistic study showed that Onjisaponin B promoted the degradation of amyloid precursor protein (APP). Further, oral administration of Onjisaponin B ameliorated Aβ pathology and behavioral defects in APP/PS1 mice. Taken together, our results indicate that Onjisaponin B is effective against AD, providing a new therapeutic agent for further drug discovery.


Current procedures for diagnosing dysphagia in elderly clients.
Intubation no longer remains the only solution to feeding problems of the elderly patient with dysphagia. Dysphagic disorders result from neurogenic, myogenic, psychogenic, or mechanical causes. Thus numerous hospitalized or institutionalized elderly patients may have dysphagic symptoms. The consequences of this disorder are significant, and aspiration pneumonia is often the outcome. Current diagnostic procedures available to identify dysphagia are discussed.


Contribution and quality of mathematical modeling evidence in World Health Organization guidelines: A systematic review.
Mathematical modeling studies are frequently conducted to guide policy in global health. However, the contribution of mathematical modeling studies to World Health Organization (WHO) guideline recommendations, and the quality of evidence contributed by these studies remains unknown. We conducted a systematic review of the WHO Guidelines Review Committee database to identify guideline recommendations that included evidence from mathematical modeling studies since inception of the Guidelines Review Committee on 1 December, 2007. We included WHO guideline recommendations citing a mathematical modeling study in the primary evidence base. We defined a mathematical model as a framework that predicted epidemiologic, health or economic impact of an intervention or decision in the clinical or public health context. The primary outcome was inclusion of evidence from mathematical modeling studies in a guideline recommendation. We evaluated each unique modeling study across multiple domains of quality. Between 1 December 2007 and 1 April 2019, the WHO Guidelines Review Committee approved 154 guidelines providing 1619 guideline recommendations. Mathematical modeling studies informed 46 WHO guidelines (29.9%) and 101 unique guideline recommendations (6.2%). Modeling evidence addressed topics related to infectious diseases in 38 guidelines (82.6%) and 81 recommendations (80.2%), most commonly for HIV and tuberculosis. Evidence from modeling studies was assessed in the GRADE evidence profile for 12 recommendations (12.9%) and GRADE evidence-to-decision framework for 45 recommendations (44.6%). Modeling-informed recommendations were more likely than other recommendations within the same guidelines to be issued with a "conditional" rather than "strong" strength of recommendation (53.5% versus 37.8%), and the evidence underlying modeling-informed recommendations was more likely to be assessed as very low quality (41.6% versus 24.1%). Upon review of individual modeling studies, we estimated that 33.8% of models performed a calibration, 29.4% of models performed a validation of results, and 20.6% of models reported a change in the study conclusion in the sensitivity analysis. While policy recommendations in WHO guidelines are informed by evidence from modeling studies, the validity of modeling studies included in guidelines development is heterogeneous. Quality assessment is needed to support the evaluation and incorporation of evidence from mathematical modeling studies in guidelines development.


Anti-tumor potential of astragalus polysaccharides on breast cancer cell line mediated by macrophage activation.
Adverse effects are pressing challenges produced by chemotherapy and radiotherapy for the treatment of breast cancer. Nontoxic herbal medicines are therefore considered as a favorable alternative. Astragalus membranaceus has attracted growing interest in the field of biomedicine thanks to its various biological activities, among which the anticancer activity is considered to be closely associated with its active component-astragalus polysaccharide (APS). Currently, direct anti-tumor activity and the activation of immune response of the host have been widely acknowledged as the mechanism by which APS exerts its anti-cancer activity. In this study, we aimed to investigate whether APS could inhibit the growth of MCF-7 cells and activate macrophages to further kill cancer cells. The results indicated that the obtained APS was a pyran-type polysaccharide, containing 89.75% total carbohydrate and a minor amount of uronic acid (9.3%). Although APS did not significantly inhibit the growth of MCF-7 cells growth, encouragingly, APS-activated RAW264.7 macrophages present anti-cancer activity as evidenced by (a) cell proliferation inhibition (with an inhibitory rate of 41%), (b) G1-phase cell cycle arrest, as well as (c) the regulation of apoptosis-related genes (Bax/Bcl-2, 13.26-fold increase than untreated cells). In addition, APS could upregulate the level of nitric oxide (NO) and tumor necrosis factor-α (TNF-α), which acted as inducers of tumor cell apoptosis. Collectively, our findings suggest that APS can activate macrophages to release NO and TNF-α, which directly blocks cancer cell growth. The anti-breast cancer effect of APS and the in vivo mechanism will be further elucidated with a review to provide a therapeutic strategy for breast cancer.


A prospective assessment of the characteristics of dysphagia in myasthenia gravis.
Fatigable muscle weakness is the clinical hallmark of the human autoimmune disease myasthenia gravis (MG). Weakness of the oropharyngeal muscles produces dysphagia, which continues to be a major source of morbidity in MG. In this study we prospectively assessed 20 patients with myasthenia gravis who described difficulties with swallowing. Videofluoroscopic assessment showed disordered swallowing in all, with abnormalities in oral, pharyngeal, and, to a lesser extent, oral preparatory phases. Of the 20 studied, 7 aspirated, most of whom did so silently. Laryngeal penetration occurred in many more patients. The characteristics of dysphagia in MG are described and compared with other neurological disorders that can produce dysphagia.


Salen-based porous aromatic frameworks with multi-active sites as anode materials for lithium-ion batteries.
Porous organic polymers are considered as excellent candidates for the electrode materials in rechargeable battery due to their desirable properties including porosity, customizable structure, and intrinsic chemical stability. Herein a Salen-based porous aromatic framework (Zn/Salen-PAF) is synthesized through a metal directed method and further used as efficient anode materialfor lithium-ion battery. Attributing to the stable functional skeleton, Zn/Salen-PAF delivers a reversible capacity of 631 mAh·g-1 at 50 mA·g-1, a high-rate capability of 157 mAh·g-1 at 20.0 A·g-1 and a long-term cycling capacity of 218 mAh·g-1 at 5.0 A·g-1 even after 2000 cycles. Compared to the Salen-PAF without metal ions, Zn/Salen-PAF possesses better electrical conductivity and more active sites. X-ray photoelectron spectroscopy (XPS) investigation indicates that the coordination of Zn2+ with N2O2 unit not only improves the conjugation of the framework but also contributes to the in situ cross-sectional oxidation of the ligand during reaction, which results in the electron redistribution of oxygen atom and the formation of CO bonds.


Latent potentials of the white-rot basidiomycete Phanerochaete chrysosporium responsible for sesquiterpene metabolism: CYP5158A1 and CYP5144C8 decorate (E)-α-bisabolene.
Basidiomycetes produce various sesquiterpenoids and their relevance for pharmaceutical and agricultural applications and understanding their biosynthetic machinery to produce these secondary metabolites have attracted significant interest. Because sesquiterpene synthases (STSs) and cytochrome P450 monooxygenases (P450s) play pivotal roles in the production of sesquiterpenoids, functional characterization of these enzymes is fundamentally essential. In this study, we found 11 possible STSs from the white-rot basidiomycete Phanerochaete chrysosporium (PcSTSs) and isolated nine of these as full-length cDNAs encoding a mature open reading frame. Using the isolated cDNAs, we performed heterologous expression of PcSTSs in Saccharomyces cerevisiae. Metabolic studies revealed that seven of the PcSTSs produce a series of sesquiterpene scaffolds, including (E)-α-bisabolene. Furthermore, we constructed a co-expression system of (E)-α-bisabolene synthase and P450 from P. chrysosporium (PcCYP). Semi-comprehensive screening using 120 isoforms of PcCYPs resulted in the identification of CYP5158A1 and CYP5144C8, two P450s capable of decorating (E)-α-bisabolene.


Breast biopsy nuclear pellets are a convenient source of DNA for routine determination of Her-2/neu gene amplification.
Cell nuclei from breast biopsies are a byproduct of routine hormone receptor determination and are usually discarded. We report here that DNA purified from this source is suitable for use in conventional Southern blot or Polymerase Chain Reaction (PCR) techniques to screen for Her-2/neu amplification, enabling efficient use of limited biopsy material.


Antimalarial activity of 2-(substituted amino)-4,6-bis(trichloromethyl)-1,3,5-triazines and N-(chlorophenyl)-N'-[4-(substituted amino)-6-(trichloromethyl)-1,3,5-triazin-2-yl]guanidines.
A series of 2-[[(dialkylamino)alkyl]amino]-4,6-bis(trichloromethyl)-1,3,5-triazines (III) and N-(4-chlorophenyl)-N'-[4-[[(dialkylamino)alkyl]amino]-6- (trichloromethyl)-1,3,5-triazin-2-yl]guanidines (IV) were prepared from 2,4,6-tris(trichloromethyl)-1,3,5-triazine and 2-chloro-4,6-bis(trichloromethyl)-1,3,5-triazine. Compounds of type III showed modest antimalarial activity while XIa with the camoquin side chain was more potent. Analogues of type IV broadly exhibited modest antimalarial activity.