Borneocola (Zingiberaceae), a new genus from Borneo.

Abstract: A new genus from Borneo, Borneocola Y.Y.Sam, is described here. The genus currently contains eight species previously classified as members of the Scaphochlamys Baker. The finding is based on the results of the morphological and molecular studies of Scaphochlamys throughout its geographical range and its closely allied sister groups, Distichochlamys M.F.Newman and Myxochlamys A.Takano & Nagam. Borneocola is nested within the tribe Zingibereae and its monophyly is strongly supported by both ITS and matK sequence data. The genus is characterised by several thin, translucent and marcescent floral bracts, absence of coloured streaks on the labellum and capitate stigma with two dorsal knobs. The genus is distributed in northwest Borneo and all species are very rare and highly endemic.

Sam|Yen Yen|YY|
Takano|Atsuko|A|
Ibrahim|Halijah|H|
Záveská|Eliška|E|
Aziz|Fazimah|F|

Scaphochlamys morphology Distichochlamys Myxochlamys phylogeny taxonomy


Qualitative Assessment of Medical Information on YouTube: A Multilingual Comparison of Common Urological Conditions.

Abstract:
INTRODUCTION
Patients nowadays often search video-sharing platforms for online patient education materials. Since previous assessments of urological videos were limited to English, we systematically assessed the quality of videos on treatment of benign prostatic hyperplasia (BPH), prostate cancer (PCa), and urinary stone disease (USD) in 4 different languages on YouTube using validated instruments.

METHODS
The search for videos on YouTube addressing treatment options of BPH, PCa, and USD was performed in October 2020 in -English, French, German, and Italian. Assessed parameters included basic data (e.g., number of views), grade of misinformation, and reporting of conflicts of interest. Quality of content was analyzed using the validated DISCERN questionnaire. Data were analyzed using descriptive statistics.

RESULTS
A total of 240 videos (60 videos in each language) were analyzed. Videos on USD in English had the highest number of views (median views 271,878 [65,313-2,513,007]). The median overall quality of videos assessed showed a moderate quality (2.5-3.4 points out of 5 points for DISCERN item 16). Median total DISCERN score of all videos divided by language showed very similar results: English (39.75 points), French (38 points), German (39.5 points), and Italian (39 points). Comparing the different diseases, videos about BPH showed the highest median scores, especially in German language (median score 43.25 points).

CONCLUSIONS
Videos concerning the treatment of BPH, PCa, and USD have a low to moderate quality of content, with no differences seen between the languages assessed. These findings further support the notion of improved patient information materials on video platforms such as YouTube.

Pratsinis|Manolis|M| Babst|Christa|C| Langenauer|Janine|J| Schmid|Hans-Peter|HP| Piller|Alberto|A| Neuenschwander|Anne|A| Betschart|Patrick|P|

YouTube
Prostate cancer
Stone disease
Patient information
Benign prostatic syndrome


Polymorphisms in PLA2G6 and PLA2G4C genes for calcium-independent phospholipase A2 do not contribute to attenuated niacin skin flush response in schizophrenia patients.

Abstract: We hypothesized that attenuated niacin skin flushing in schizophrenia patients might be associated with polymorphic variants in PLA2G6 and PLA2G4C genes (rs4375 and rs1549637 variations) which encode calcium-independent phospholipase A2 beta (iPLA2β) and cytosolic phospholipase A2 gamma (cPLA2γ) enzymes. The iPLA2β and cPLA2γ may play an important role in niacin-mediated signaling; in addition to their major role - mediating phospholipids remodeling, which alters membrane receptors and signal transduction, they regulate the reservoir of arachidonic acid for prostaglandins synthesis. Skin response to topical niacin of 0.1M, 0.01M, 0.001M and 0.0001M concentrations in 75 schizophrenia patients was rated using the method of volumetric niacin response (VNR). Neither PLA2G6 nor PLA2G4C gene polymorphisms were significantly associated with VNR values. Furthermore, polymorphisms׳ synergy on niacin skin flushing was also not detected.

Niacin skin flush response
Schizophrenia
PLA2G4C gene polymorphism
PLA2G6 gene polymorphism


The Diagnostic Usefulness of Serum Total Bile Acid Concentrations in the Early Phase of Acute Pancreatitis of Varied Etiologies.

Abstract: The most common causes of acute pancreatitis (AP) are biliary tract diseases with cholestasis and alcohol consumption. In 10%-15% of patients, etiology determination is difficult. Identification of the etiology allows for the implementation of adequate treatment. The aim of this study was to assess the utility of the serum concentrations of total bile acids (TBA) to diagnose AP etiology in the early phase of the disease. We included 66 patients with AP, admitted within the first 24 h from the onset of symptoms. TBA were measured in serum at 24, 48, and 72 h from the onset of AP, using an automated fifth generation assay. The bilirubin-to-TBA ratio (B/TBA) was calculated. TBA was highest on the first day of AP and decreased subsequently. In patients with biliary etiology, serum TBA was significantly higher compared to those with alcoholic and other etiologies. B/TBA was significantly higher in patients with alcoholic etiology. At admission, the cut-off values of 4.7 µmol/L for TBA and 4.22 for the B/TBA ratio allowed for a differentiation between biliary and other etiologies of AP with a diagnostic accuracy of 85 and 83%. Both TBA and B/TBA may help in the diagnosis of AP etiology in the early phase of AP.

Maleszka|Aleksandra|A| Dumnicka|Paulina|P| Matuszyk|Aleksandra|A| Pędziwiatr|Michał|M| Mazur-Laskowska|Małgorzata|M| Sporek|Mateusz|M| Ceranowicz|Piotr|P| Olszanecki|Rafał|R| Kuźniewski|Marek|M| Kuśnierz-Cabala|Beata|B|

total bile acids
biliary acute pancreatitis
idiopathic acute pancreatitis


Cadmium exposure and cognitive abilities and behavior at 10 years of age: A prospective cohort study.

Abstract:
BACKGROUND
We have previously reported inverse associations of prenatal and childhood cadmium exposure with cognition in 5-year-old Bangladeshi children.

OBJECTIVES
To assess if cadmium exposure affected cognition and behavior in the Bangladeshi children at 10 years.

METHODS
Cadmium exposure was assessed by urinary concentrations at 10 (n = 1498) and 5 years of age (n = 1453), and of the mothers in early pregnancy (n = 1299), measured by ICP-MS. Cognitive abilities were assessed with Wechsler Intelligence Scale for Children (4th edition) and behavior with the parent-rated Strengths and Difficulties Questionnaire.

RESULTS
In multivariable-adjusted models, urinary cadmium at 10 years was inversely associated with Full scale IQ and most of the sub-scales. Associations were mainly observed in boys, in whom the difference in Full scale IQ was 7.0 scores (95% CI: -11, -2.7), corresponding to 0.21 SD, when comparing those in the highest (range: 0.30-2.6 μg/L) and lowest tertile of urinary cadmium (0.036-0.18 μg/L). Urinary cadmium at 5 years was inversely, but not significantly, associated with IQ. Children in the highest exposure tertile at 10 years also had poorer Prosocial behavior scores. The association appeared strongest in girls, in whom the corresponding OR for Prosocial scores in relation to cadmium exposure at 10 years and prenatally was 0.58 (95% CI: 0.34, 0.99) and 0.48 (95% CI: 0.25, 0.93), respectively.

CONCLUSION
Childhood cadmium exposure was associated with lower intelligence in boys, and there were indications of altered behavior in girls for both prenatal and childhood exposures. Findings are of concern as similar exposure levels are common world-wide.

Gustin|Klara|K| Tofail|Fahmida|F| Vahter|Marie|M| Kippler|Maria|M|

D011297:Prenatal Exposure Delayed Effects

Cadmium
Child IQ
Development
Food pollutant
Neurotoxicity
Urine


Drivers of harmful algal blooms in coastal areas of Eastern Mediterranean: a machine learning methodological approach.

Abstract: Harmful algal species are present in the Mediterranean Sea and are often associated with toxic events affecting the nearby coastal zones. The presence of 18 marine microalgae, at genus level, associated with potentially harmful characteristics was predicted using a number of machine learning techniques based exclusively on a small set of abiotic variables, already identified as drivers of blooms. Random Forest (RF) algorithm achieved the best predictive performance by correctly identifying the presence of most genera with a mean of 89.2% of total samples. Although, RF has shown lower predictive performance for genera present in a low number of samples, its predictive power remains at least "fair' in these cases. The main tree-based advantage of RF was thereafter used to assess the importance of the input variables in predicting the presence of the algal genera. Temperature had the most powerful effect on genera's presences, although this effect varies among genera. Finally, the genera were clustered based on their response to the considered abiotic variables and common trends in an ecological context were identified.

Tamvakis|Androniki|A|
Tsirtsis|George|G|
Karydis|Michael|M|
Patsidis|Kleanthis|K|
Kokkoris|Giorgos D|GD|

D057097:Harmful Algal Bloom
D000069550:Machine Learning
D013696:Temperature

harmful algal
Eastern Mediterranean
machine learning
Random Forest
abiotic parameters


Implementation of an easy-to-follow standardized chart for free flaps clinical monitoring during the start of a head and neck microsurgery unit in a tertiary hospital.

Abstract: Successful head and neck reconstructive microsurgery requires a multidisciplinary approach involving specialists such as maxillofacial surgeons, plastic surgeons, otolaryngologists, anaesthesiologists, and nurses. It requires strict perioperative management of the patient, with special attention paid to parameters such as blood pressure, ventilation, and bleeding, which can all impact flap perfusion. In high-volume centers, specially-trained microsurgery units are available for optimal control of flap monitoring and management of all aspects of patient care. However, during the beginning of a microsurgery unit at a hospital unfamiliar with the demands of this field, easy-to-follow, but effective, measures must be in place to ensure adoption and adherence to post-operative care principles that confer higher success rates in head and neck cancer patients undergoing free flap reconstruction. While frequent observations can be labor-intensive, clinical monitoring remains the most suitable method during this early period and requires appropriate experience to be effective. Our aim is to emphasize the importance of clinical monitoring during the beginnings of a microsurgery unit by introducing an easy-to-follow clinical monitoring chart that covers both intraluminal and extraluminal causes of free flap compromise.

Megías Barrera|J|J|
Gorina Faz|M|M|
Artajona García|M|M|
Costa Garcia|A|A|
Navarrete Piñero|M|M|

Head and neck microsurgery
Monitoring chart
Free flap monitoring


Viscous dynamics of drops and bubbles in Hele-Shaw cells: Drainage, drag friction, coalescence, and bursting.

Abstract: In this review article, we discuss recent studies on drops and bubbles in Hele-Shaw cells, focusing on how scaling laws exhibit crossovers from the three-dimensional counterparts and focusing on topics in which viscosity plays an important role. By virtue of progresses in analytical theory and high-speed imaging, dynamics of drops and bubbles have actively been studied with the aid of scaling arguments. However, compared with three-dimensional problems, studies on the corresponding problems in Hele-Shaw cells are still limited. This review demonstrates that the effect of confinement in the Hele-Shaw cell introduces new physics allowing different scaling regimes to appear. For this purpose, we discuss various examples that are potentially important for industrial applications handling drops and bubbles in confined spaces by showing agreement between experiments and scaling theories. As a result, this review provides a collection of problems in hydrodynamics that may be analytically solved or that may be worth studying numerically in the near future.

Viscous dynamics
Drops and bubbles
Hele-Shaw cell
Scaling laws
Thin film


Repeat limited fasciectomy is a safe and effective treatment for recurrence of Dupuytren's disease.

Abstract:
AIMS
The results of surgery for Dupuytren's disease can be compromised by the potential for disease recurrence and loss of function. Selecting which patients will benefit from repeat surgery, when to operate, and what procedure to undertake requires judgement and an understanding of patient expectations and functional needs. We undertook this study to investigate patient outcomes and satisfaction following repeat limited fasciectomy for recurrent Dupuytren's disease.

METHODS
We prospectively identified all patients presenting with recurrence of Dupuytren's disease who were selected for surgical treatment with repeat limited fasciectomy surgery between January 2013 and February 2015. Patients were assessed preoperatively, and again at a minimum of five years postoperatively. We identified 43 patients who were carefully selected for repeat fasciectomy involving 54 fingers. Patients with severe or aggressive disease with extensive skin involvement were not included; in our practice, these patients are instead counselled and preferentially treated with dermofasciectomy. The primary outcome measured was change in the Michigan Hand Outcomes Questionnaire (MHQ) score. Secondary outcomes were change in finger range of motion, flexion contracture, Semmes-Weinstein monofilament (SWM) values, and overall satisfaction.

RESULTS
There was a significant improvement in MHQ scores, across all domains, with a mean overall score increase of 24 points (p < 0.001). The summed flexion contracture across the metacarpophalangeal joint (MCPJ) and the proximal interphalangeal joint (PIPJ) reduced from means of 72.0° (SD 15.9°) to 5.6° (SD 6.8°) (p < 0.001). A significant increase in maximal flexion was seen at the MCPJ (p < 0.001) but not the PIPJ (p = 0.550). The mean overall satisfaction score from the visual analogue scale was 8.9 (7.9 to 10.0). Complications were uncommon although five fingers showed reduced sensibility at final follow-up.

CONCLUSION
Our study shows that repeat limited fasciectomy for selected patients presenting with recurrence of Dupuytren's disease can be an effective and safe treatment resulting in excellent patient-reported outcomes and levels of satisfaction. Cite this article: Bone Joint J 2021;103-B(5):946-950.

Ashdown|Thomas|T|
Hayter|Edward|E|
Morris|James A|JA|
Clough|Oliver T|OT|
Little|Maximillian|M|
Hardman|John|J|
Anakwe|Raymond E|RE|

Recurrence
Dupuytren’s disease
Finger contracture
Hand function


Zinc as chaperone-mimicking agent for retardation of amyloid β peptide fibril formation.

Abstract: Metal ions have emerged to play a key role in the aggregation process of amyloid β (Aβ) peptide that is closely related to the pathogenesis of Alzheimer's disease. A detailed understanding of the underlying mechanistic process of peptide-metal interactions, however, has been challenging to obtain. By applying a combination of NMR relaxation dispersion and fluorescence kinetics methods we have investigated quantitatively the thermodynamic Aβ-Zn(2+) binding features as well as how Zn(2+) modulates the nucleation mechanism of the aggregation process. Our results show that, under near-physiological conditions, substoichiometric amounts of Zn(2+) effectively retard the generation of amyloid fibrils. A global kinetic profile analysis reveals that in the absence of zinc Aβ40 aggregation is driven by a monomer-dependent secondary nucleation process in addition to fibril-end elongation. In the presence of Zn(2+), the elongation rate is reduced, resulting in reduction of the aggregation rate, but not a complete inhibition of amyloid formation. We show that Zn(2+) transiently binds to residues in the N terminus of the monomeric peptide. A thermodynamic analysis supports a model where the N terminus is folded around the Zn(2+) ion, forming a marginally stable, short-lived folded Aβ40 species. This conformation is highly dynamic and only a few percent of the peptide molecules adopt this structure at any given time point. Our findings suggest that the folded Aβ40-Zn(2+) complex modulates the fibril ends, where elongation takes place, which efficiently retards fibril formation. In this conceptual framework we propose that zinc adopts the role of a minimal antiaggregation chaperone for Aβ40.

D000544:Alzheimer Disease
D016229:Amyloid beta-Peptides
D006801:Humans
D007700:Kinetics
D008956:Models, Chemical
D018832:Molecular Chaperones
D010446:Peptide Fragments
D066329:Protein Aggregates
D017434:Protein Structure, Tertiary
D015032:Zinc

NMR relaxation
Alzheimer’s disease
aggregation kinetics
amyloid beta peptide
zinc ion interactions


Low bone mineral density on DXA and slipped capital femoral epiphysis as rare presentation in a child with Rubinstein-Taybi syndrome.

Abstract: We present a 7-year-old girl with Rubinstein-Taybi syndrome (RTS) and slipped capital femoral epiphysis (SCFE). She underwent bilateral arthroscopy with implant fixation for the SCFE and the symptoms resolved. This was followed by fracture of the femur after minor trauma. Dual energy X-ray absorptiometry (DXA) scan done to evaluate her bone health revealed a low bone mineral density (BMD). Our case highlights the finding of low BMD on DXA and rare association of SCFE in a child with RTS. The conundrum in this case is whether this child can be labelled to have osteoporosis as defined by the criteria given by the International Society for Clinical Densitometry guidelines.

D060048:Slipped Capital Femoral Epiphyses


Male Anabolic Androgenic Steroid Users with Personality Disorders Report More Aggressive Feelings, Suicidal Thoughts, and Criminality.

Abstract: Background and objectives: Anabolic androgenic steroids (AAS) are mainly used for aesthetic and performance-enhancing reasons. Their use is a growing public health problem and concern for society because of their adverse effects. The primary aim of this study was to identify psychiatric and personality disorders and to measure anxiety and depression in AAS users. Materials and Methods: Fifty-six males who actively contacted the Anti-Doping Hot-Line and wished to stop using AAS were included. Structured Clinical Interviews Diagnosis-I and -II were used to diagnose psychiatric and personality disorders. The Brief Scale for Anxiety and Montgomery Asberg Depression Rating Scale (subscales from the Comprehensive Psychopathological Rating Scale) were used to measure changes in anxiety and depression. Structured Clinical Interviews Diagnosis-I and -II were performed at one time point. Anxiety and depression were measured at inclusion and after six months. Urine samples were collected for an analysis of AAS and drugs of abuse. Results: All participants reported some adverse effects that they associated with AAS use. In total, 56% and 52% of the cohort fulfilled the criteria for Structured Clinical Interviews Diagnosis-I and -II diagnoses, respectively. A significantly increased risk of reporting aggressive feelings/behaviors (Odds Ratio (OR) = 4.9; Confidence Interval (CI) 0.99-25, p = 0.04), suicidal thoughts/attempts (OR = 4.6, CI 95; 0.99-21, p = 0.04) and criminality (OR = 6.5, CI 1-39, p = 0.03) was found among individuals with AAS use fulfilling the criteria for personality disorders compared with those without such AAS use. The Brief Scale for Anxiety score decreased from the median of 15 at inclusion to 10 at the follow-up visit six months later (p = 0.01, n = 19). Conclusions: Our findings indicate that among individuals with AAS use, those with a personality disorder report more aggressive behaviors, suicidal thoughts/suicidal attempts, and criminality than those without a personality disorder.

Börjesson|Annica|A|0000-0003-0159-7315 Möller|Christian|C| Hagelin|Anders|A| Vicente|Veronica|V| Rane|Anders|A| Lehtihet|Mikael|M| Dahl|Marja-Liisa|ML| Gårevik|Nina|N| Ekström|Lena|L|

comprehensive psychopathological rating scale

adverse effects of psychiatric disorders


Parallelized volumetric fluorescence microscopy with a reconfigurable coded incoherent light-sheet array.

Abstract: Parallelized fluorescence imaging has been a long-standing pursuit that can address the unmet need for a comprehensive three-dimensional (3D) visualization of dynamical biological processes with minimal photodamage. However, the available approaches are limited to incomplete parallelization in only two dimensions or sparse sampling in three dimensions. We hereby develop a novel fluorescence imaging approach, called coded light-sheet array microscopy (CLAM), which allows complete parallelized 3D imaging without mechanical scanning. Harnessing the concept of an "infinity mirror", CLAM generates a light-sheet array with controllable sheet density and degree of coherence. Thus, CLAM circumvents the common complications of multiple coherent light-sheet generation in terms of dedicated wavefront engineering and mechanical dithering/scanning. Moreover, the encoding of multiplexed optical sections in CLAM allows the synchronous capture of all sectioned images within the imaged volume. We demonstrate the utility of CLAM in different imaging scenarios, including a light-scattering medium, an optically cleared tissue, and microparticles in fluidic flow. CLAM can maximize the signal-to-noise ratio and the spatial duty cycle, and also provides a further reduction in photobleaching compared to the major scanning-based 3D imaging systems. The flexible implementation of CLAM regarding both hardware and software ensures compatibility with any light-sheet imaging modality and could thus be instrumental in a multitude of areas in biological research.


Flow regulation effects on the hydrogeochemistry of the hyporheic zone in boreal rivers.

Abstract: River-aquifer interfaces are essential for ecosystem functioning in terms of nutrient exchange and biological habitat, but are greatly threatened world-wide. This study examined geochemical aspects of river-aquifer interaction in one regulated and one unregulated boreal river in Northern Sweden to determine whether the geochemical functioning of the hyporheic zone is affected by hydrological alterations, e.g. regulated river discharge and river-aquifer connectivity. In the unregulated Kalix River, the hyporheic pore water was well-oxygenated with orthogonal fluxes (≈0.6-0.7 m d(-1)) and acted as a sink for Fe, Mn, Al, NH4, and Ca, with fractional losses of 95%, 92%, 45%, 31%, and 15%, respectively. A corresponding elevation in the concentrations of these elements in the hyporheic sediment was observed, with higher saturation indices of Fe-, Mn-, and Al-bearing secondary minerals in hyporheic waters. In the regulated Lule River, hydraulic connectivity at the river-aquifer interface was altered by the presence of a clogging layer (0.04 m d(-1)). In addition, the river discharge oscillated daily, severely reducing exchange flows across the riverbed (<0.01 m d(-1)). As a result, the hyporheic pore water was suboxic, with elevated concentrations of filtered Fe and Mn (fractional increases of ≈3700% and ≈2500%, respectively) and other solutes (NH4, Si, S, Ca). A conceptual model revealed functional differences between geochemical features of the hyporheic zone of regulated and unregulated rivers. Overall, the results showed that hyporheic processes are altered along regulated rivers, with resulting impacts on the geochemistry of riverine, riparian and related marine ecosystems.

Siergieiev|D|D| Widerlund|A|A| Ingri|J|J| Lundberg|A|A| Öhlander|B|B|

Interface
Exchange
Kalix River
Lule River
Hydropower
PHREEQC


Neurobehavioural Changes in a Hemiparkinsonian Rat Model Induced by Rotenone.

Abstract:
INTRODUCTION
Rotenone, a mitochondrial complex I inhibitor is used as a neurotoxin agent to reproduce the neuropathological, and behavioural feature of Parkinson's Disease (PD) in rat. Due to acute and chronic exposure of rotenone with various doses through different routes of administration, mortality is being reported. Low dose takes a longer duration to produce PD symptoms in animals. This present study was designed to create hemiparkinsonian 'partial' lesion model by rotenone at a single moderate dose in two sites of striatum in albino rats and also to assess its toxicity by behavioural parameters and by microscopic study.

AIM
To assess all the motor deficits in lesioned animals that are due to the depletion of dopaminergic neurons or its terminals, the lesioned animals were administered with anti-parkinsonian drug, Levodopa which should counteract motor deficits in rats.

MATERIALS AND METHODS
The unilateral partially lesioned PD model was induced by rotenone stereotaxically into two sites of striatum of male Wistar albino rats at a dosage of 25 μg of rotenone/site. Rats were tested for its neurobehavioural activity on 7th day, 14th day, 21st day and on 30th day after rotenone infusion and compared with the sham group and sacrificed on 21st and 30th day for microscopic studies. L-DOPA was administered from 21st day to 30th day after lesion and compared with the lesioned group for the motor performance and sacrificed on 30th day for histology. Statistical analysis using One-way Analysis of variance followed by Tukey's test was applied for behavioural studies.

RESULTS
Statistical analysis showed that the signs and symptoms like motor in-coordination and postural disturbances are highly significant (p<0.05) on 14th and 21st day after administration of rotenone when compared to sham group. In L-DOPA treated rats, all the motor deficits were reversed. The neuronal cell death was minimal and sprouting of nerve terminals was detected. In lesioned group, the degeneration of nerve terminals and striatal neurons were in progressive manner.

CONCLUSION
These findings suggest that intrastriatal infusion of rotenone at a moderate dose could be used for producing hemiparkinsonian partially lesioned animal model without any mortality. Hence, this model is suitable for evaluating behavioural studies and in drug screening programs even for a long term study.

Maniyath|Sukala Puthuparambil|SP|
Solaiappan|Narayanan|N|
Rathinasamy|Muthusamy|M|

Parkinsonism
Striatum
Wistar albino rats
Complex I- inhibitor


Bidirectional regulation between TMEFF2 and STAT3 may contribute to Helicobacter pylori-associated gastric carcinogenesis.

Abstract: The transmembrane protein with epidermal growth factor and two follistatin motifs 2 (TMEFF2) is a single-pass transmembrane protein, and it is downregulated in human gastric cancer and levels correlate with tumor progression and time of survival. However, the mechanism of its dysregulation in gastric cancer is little known. Here we investigate its regulatory mechanism and the bidirectional regulation between TMEFF2 and STAT3 in gastric carcinogenesis. TMEFF2 expression was decreased after Helicobacter pylori (H. pylori) infection in vivo and in vitro. STAT3 directly binds to the promoter of TMEFF2 and regulates H. pylori-induced TMEFF2 downregulation in normal gastric GES-1 cells and gastric cancer AGS cells. Conversely, TMEFF2 may suppress the phosphorylation of STAT3 and TMEFF2-induced downregulation of STAT3 phosphorylation may depend on SHP-1. A highly inverse correlation between the expression of TMEFF2 and pSTAT3 was also revealed in gastric tissues. We now show the deregulation mechanism of TMEFF2 in gastric carcinogenesis and identify TMEFF2 as a new target gene of STAT3. The phosphorylation of STAT3 may be negatively regulated by TMEFF2, and the bidirectional regulation between TMEFF2 and STAT3 may contribute to H. pylori-associated gastric carcinogenesis.

Sun|Tian-Tian|TT| Tang|Jia-Yin|JY| Du|Wan|W| Zhao|Hui-Jun|HJ| Zhao|Gang|G| Yang|Sheng-Li|SL| Chen|Hao-Yan|HY| Hong|Jie|J| Fang|Jing-Yuan|JY|

D015972:Gene Expression Regulation, Neoplastic

D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6

D060888:Real-Time Polymerase Chain Reaction

D020133:Reverse Transcriptase Polymerase Chain Reaction


Indirect effects of habitat disturbance on invasion: nutritious litter from a grazing resistant plant favors alien over native Collembola.

Abstract: Biological invasions are major threats to biodiversity, with impacts that may be compounded by other forms of environmental change. Observations of high density of the invasive springtail (Collembola), Hypogastrura manubrialis in heavily grazed renosterveld vegetation in the Western Cape, South Africa, raised the question of whether the invasion was favored by changes in plant litter quality associated with habitat disturbance in this vegetation type. To examine the likely mechanisms underlying the high abundance of H. manubrialis, cages with three types of naturally occurring litter with different nutrient content were placed out in the area and collected after different periods of time. Hypogastrura manubrialis was mainly found in the nutrient-rich litter of the yellowbush (Galenia africana), which responds positively to disturbance in the form of overgrazing. This suggests that invasion may have been facilitated by a positive interaction with this grazing resistant plant. By contrast, indigenous Collembola were least abundant in yellowbush litter. Negative correlations between high abundance of H. manubrialis and the abundance and diversity of other species suggest that competitive interactions might underlie low abundance of these other species at the patch level. Group behavior enables H. manubrialis to utilize efficiently this ephemeral, high quality resource, and might improve its competitive ability. The results suggest that interactions among environmental change drivers may lead to unforeseen invasion effects. H. manubrialis is not likely to be very successful in un-grazed renosterveld, but in combination with grazing, favoring the nutrient-rich yellowbush, it may become highly invasive. Field manipulations are required to fully verify these conclusions.

Leinaas|Hans Petter|HP|
Bengtsson|Jan|J|
Janion-Scheepers|Charlene|C|
Chown|Steven L|SL|

renosterveld
South Africa
Facilitation
nonadditive effects
resource patchiness


The importance of ribosome production, and the 5S RNP-MDM2 pathway, in health and disease.

Abstract: Ribosomes are abundant, large RNA-protein complexes that are the source of all protein synthesis in the cell. The production of ribosomes is an extremely energetically expensive cellular process that has long been linked to human health and disease. More recently, it has been shown that ribosome biogenesis is intimately linked to multiple cellular signalling pathways and that defects in ribosome production can lead to a wide variety of human diseases. Furthermore, changes in ribosome production in response to nutrient levels in the diet lead to metabolic re-programming of the liver. Reduced or abnormal ribosome production in response to cellular stress or mutations in genes encoding factors critical for ribosome biogenesis causes the activation of the tumour suppressor p53, which leads to re-programming of cellular transcription. The ribosomal assembly intermediate 5S RNP (ribonucleoprotein particle), containing RPL5, RPL11 and the 5S rRNA, accumulates when ribosome biogenesis is blocked. The excess 5S RNP binds to murine double minute 2 (MDM2), the main p53-suppressor in the cell, inhibiting its function and leading to p53 activation. Here, we discuss the involvement of ribosome biogenesis in the homoeostasis of p53 in the cell and in human health and disease.

Pelava|Andria|A|
Schneider|Claudia|C|
Watkins|Nicholas J|NJ|

ribosome
p53
5S RNP
MDM2
nucleolus
ribosomal protein


Evaluation of the effect of three mouthwashes on the mechanical properties and surface morphology of several orthodontic wires: An in vitro study.

Abstract:
BACKGROUND
The aim of this study was to evaluate and compare the changes in the mechanical properties and surface morphology of different orthodontic wires after immersion in three mouthwash solutions.

MATERIALS AND METHODS
In this in vitro study, five specimens of each of 0.016 inch nickel titanium (NiTi), coated NiTi, and stainless steel orthodontic wires were selected. The specimens were immersed in 0.05% sodium fluoride (NaF), 0.2% chlorhexidine, Zataria multiflora extract, and distilled water (control) for 1.5 h at 37°C. After immersion, loading and unloading forces at 0.5 mm intervals and the elastic modulus (E) of the wires were measured using a three-point bending test. Surface changes were observed with a scanning electron microscope (SEM). Two-way analysis of variance and Bonferroni tests were used to compare the properties of the wires. The level of significance was set at 0.05.

RESULTS
Statistically significant changes in loading and unloading forces and E of the orthodontic wires were observed after immersion in different mouthwash solutions (P < 0.05). A pairwise comparison showed a nonsignificant difference between the effect of different mouthwashes on the E of different types of wires (P > 0.05). SEM images showed surface changes in some types ofthe orthodontic wires.

CONCLUSION
The mouthwashes used in this study seemed to change the mechanical properties and surface quality of the orthodontic wires.

mouthwashes
orthodontic wire
Elastic modulus
mechanical processes


Post-hoc analysis of vitamin D status and reduced risk of preterm birth in two vitamin D pregnancy cohorts compared with South Carolina March of Dimes 2009-2011 rates.

Abstract:
BACKGROUND
Two vitamin D pregnancy supplementation trials were recently undertaken in South Carolina: The NICHD (n=346) and Thrasher Research Fund (TRF, n=163) studies. The findings suggest increased dosages of supplemental vitamin D were associated with improved health outcomes of both mother and newborn, including risk of preterm birth (<37 weeks gestation). How that risk was associated with 25(OH)D serum concentration, a better indicator of vitamin D status than dosage, by race/ethnic group and the potential impact in the community was not previously explored. While a recent IOM report suggested a concentration of 20 ng/mL should be targeted, more recent work suggests optimal conversion of 25(OH)D-1,25(OH)2D takes place at 40 ng/mL in pregnant women.

OBJECTIVE
Post-hoc analysis of the relationship between 25(OH)D concentration and preterm birth rates in the NICHD and TRF studies with comparison to Charleston County, South Carolina March of Dimes (CC-MOD) published rates of preterm birth to assess potential risk reduction in the community.

METHODS
Using the combined cohort datasets (n=509), preterm birth rates both for the overall population and for the subpopulations achieving 25(OH)D concentrations of ≤20 ng/mL, >20 to <40 ng/mL, and ≥40 ng/mL were calculated; subpopulations broken down by race/ethnicity were also examined. Log-binomial regression was used to test if an association between 25(OH)D serum concentration and preterm birth was present when adjusted for covariates; locally weighted regression (LOESS) was used to explore the relationship between 25(OH)D concentration and gestational age (weeks) at delivery in more detail. These rates were compared with 2009-2011 CC-MOD data to assess potential risk reductions in preterm birth.

RESULTS
Women with serum 25(OH)D concentrations ≥40 ng/mL (n=233) had a 57% lower risk of preterm birth compared to those with concentrations ≤20 ng/mL [n=82; RR=0.43, 95% confidence interval (CI)=0.22,0.83]; this lower risk was essentially unchanged after adjusting for covariates (RR=0.41, 95% CI=0.20,0.86). The fitted LOESS curve shows gestation week at birth initially rising steadily with increasing 25(OH)D and then plateauing at ∼40 ng/mL. Broken down by race/ethnicity, there was a 79% lower risk of preterm birth among Hispanic women with 25(OH)D concentrations ≥40 ng/mL (n=92) compared to those with 25(OH)D concentrations ≤20 ng/mL (n=29; RR=0.21, 95% CI=0.06,0.69) and a 45% lower risk among Black women (n=52 and n=50; RR=0.55, 95% CI=0.17,1.76). There were too few white women with low 25(OH)D concentrations for assessment (n=3). Differences by race/ethnicity were not statistically significant with 25(OH)D included as a covariate. Compared to the CC-MOD reference group, women with serum concentrations ≥40 ng/mL in the combined cohort had a 46% lower rate of preterm birth overall (n=233, p=0.004) with a 66% lower rate among Hispanic women (n=92, p=0.01) and a 58% lower rate among black women (n=52, p=0.04).

CONCLUSIONS
In this post-hoc analysis, achieving a 25(OH)D serum concentration ≥40 ng/mL significantly decreased the risk of preterm birth compared to ≤20 ng/mL. These findings suggest the importance of raising 25(OH)D levels substantially above 20 ng/mL; reaching 40 ng/mL during pregnancy would reduce the risk of preterm birth and achieve the maximal production of the active hormone.

Wagner|C L|CL|
Baggerly|C|C|
McDonnell|S|S|
Baggerly|K A|KA|
French|C B|CB|
Baggerly|L|L|
Hamilton|S A|SA|
Hollis|B W|BW|

Vitamin D
Preterm birth
March of Dimes
Cholecalciferol
Pregnancy health outcomes


A bacterial immunomodulatory protein with lipocalin-like domains facilitates host-bacteria mutualism in larval zebrafish.

Abstract: Stable mutualism between a host and its resident bacteria requires a moderated immune response to control bacterial population size without eliciting excessive inflammation that could harm both partners. Little is known about the specific molecular mechanisms utilized by bacterial mutualists to temper their hosts' responses and protect themselves from aggressive immune attack. Using a gnotobiotic larval zebrafish model, we identified an Aeromonas secreted immunomodulatory protein, AimA. AimA is required during colonization to prevent intestinal inflammation that simultaneously compromises both bacterial and host survival. Administration of exogenous AimA prevents excessive intestinal neutrophil accumulation and protects against septic shock in models of both bacterially and chemically induced intestinal inflammation. We determined the molecular structure of AimA, which revealed two related calycin-like domains with structural similarity to the mammalian immune modulatory protein, lipocalin-2. As a secreted bacterial protein required by both partners for optimal fitness, AimA is an exemplar bacterial mutualism factor.

mutualism
zebrafish
inflammation
Aeromonas
immunology
infectious disease
lipocalin
microbiology
microbiota


The GHR-R antagonist JMV 2959 neither induces malaise nor alters the malaise property of LiCl in the adult male rat.

Abstract: The orexigenic peptide ghrelin (GHR) interacts with ghrelin receptors (GHR-Rs) to modulate brain reinforcement and feeding circuits. Pharmacological inactivation of GHR-Rs via administration of the drug JMV 2959 attenuates the rewarding/reinforcing effects of several drugs of abuse including alcohol, morphine, amphetamine and nicotine. One view of these results is that inactivation of GHR-Rs taps into brain reinforcement/feeding circuits acted upon by drugs of abuse. An alternate explanation is that JMV 2959 may induce malaise, which in turn may limit reinforcement as well as food ingestion. This is a variable of interest given that nicotine alone can induce malaise which may be enhanced by JMV 2959. In the present study, we assessed the capacity of JMV 2959 to produce malaise using a conditioned taste aversion (CTA) task. Adult male rats were allowed to consume a 0.1% sodium saccharin solution and then injected IP with either vehicle, 0.4mg/kg nicotine, 3mg/kg JMV 2959, a combination of 0.4mg/kg nicotine and 3mg/kg JMV 2959, or 32mg/kg lithium chloride (a positive control known to support induction of CTA). Lithium chloride produced a robust avoidance of the saccharin solution in subsequent 2 bottle (water and saccharin) tests, whereas JMV 2959 alone did not induce CTA. The combination of JMV 2959 and nicotine induced a moderate degree of CTA that was similar to that produced by nicotine alone. These results suggest that JMV 2959 is unlikely to limit either reinforcement or food ingestion via induction of malaise.

Rodriguez|Juan A|JA|
Fehrentz|Jean-Alain|JA|
Martinez|Jean|J|
Ben Haj Salah|Khoubaib|K|
Wellman|Paul J|PJ|


Infections with Centrocestus armatus Metacercariae in Fishes from Water Systems of Major Rivers in Republic of Korea.

Abstract: The infection status of Centrocestus armatus metacercariae (CaMc) was broadly surveyed in freshwater fishes from major river systems in the Republic of Korea (Korea) during 2008-2017. A total of 14,977 fishes was caught and examined by the artificial digestion method. CaMc were detected in 3,818 (97.1%) (2,114 Z. platypus: 96.1% and 1,704 Z. temminckii: 98.4%) out of 3,932 Zacco spp. examined and their density was 1,867 (2,109 in Z. platypus and 1,567 in Z. temminckii) per fish infected. The prevalences with CaMc were high, 93.7-100%, in Zacco spp. from all surveyed areas. However, their densities were more or less different by the surveyed areas and fish species. They were most high in Nakdong-gang in Gyeongsangnam-do (4,201 in average), and followed by Geum-gang (2,343), Nakdong-gang in Gyeongsangbuk-do (1,623), Han-gang (1,564), Tamjin-gang and Yeongsan-gang (1,540), streams in the east coast (1,028), Seomjin-gang (488) and Mangyeong-gang (170). In another species of rasborinid fish, Opsariichthys uncirostris amurensis, CaMc were detected in 222 (74.8%) out of 297 ones examined and their density was 278 (1-4,480) per fish infected. CaMc were also detected in total 41 fish species except for the rasborinid fish, Z. platypus, Z. temminckii and O. uncirostris amurensis. Conclusively, it was confirmed that among the 3 species of rasborinid fish, Z. platypus and Z. temminckii are highly prevalent and O. uncirostris amurensis is moderately prevalent with CaMc. Additionally, we could know that variety of fish species act as the second intermediate hosts of C. armatus in Korea.

Sohn|Woon-Mok|WM|
Na|Byoung-Kuk|BK|
Cho|Shin-Hyeong|SH|
Ju|Jung-Won|JW|
Kim|Cheon-Hyeon|CH|
Yoon|Ki-Bok|KB|
Kim|Jai-Dong|JD|
Son|Dong Cheol|DC|
Lee|Soon-Won|SW|

Centrocestus armatus
metacercaria
river
Opsariichthys uncirostris amurensis
Zacco platypus
Zacco temminckii


Quercetin and tin protoporphyrin attenuate hepatic ischemia reperfusion injury: role of HO-1.

Abstract: Ischemia reperfusion (IR) injury occurs in many clinical situations such as organ transplantation and hepatectomies resulting in oxidative stress and immune activation. Heme oxygenase-1(HO-1) is the rate-limiting step in the heme-degradation pathway and has a critical cytoprotective role. Induction of HO-1 improves liver I/R injury. Quercetin, a plant pigment (flavonoid), is an antioxidant and HO-1 inducer. Tin protoporphyrin (SnPP) is a HO-1 inhibitor. This study was designed to investigate the protective effect of quercetin in hepatic I/R injury and the role of HO-1. Wister rats were randomly divided into four groups (sham, I/R, quercetin, and SnPP). Liver ischemia was induced for 45 min then reperfusion was allowed for 1 h. Quercetin and surprisingly SnPP ameliorate the deleterious effect of I/R by reducing the oxidative stress and hepatocyte degeneration. Both agents decreased the elevated inflammatory cytokines and improved the inhibition of the antiapoptotic marker, Bcl2. They induced HO-1 content and expression. Quercetin has better cytoprotective effect than SnPP. These findings suggest that quercetin has a hepatoprotective effect against I/R injury via HO-1 induction and unexpectedly, SnPP showed the similar effect. Quercetin has more prominent protective effect than SnPP because of its superior ability to induce HO-1.

Atef|Yara|Y|
El-Fayoumi|Hassan M|HM|
Abdel-Mottaleb|Yousra|Y|
Mahmoud|Mona F|MF|

Quercetin
Tin protoporphyrin
Ischemia reperfusion
Ho-1


Design, synthesis, and systematic evaluation of 4-arylpiperazine- and 4-benzylpiperidine napthyl ethers as inhibitors of monoamine neurotransmitters reuptake.

Abstract: Two series of 4-arylpiperazine- and 4-benzylpiperidine naphthyl ethers were designed based on structure-activity relationship (SAR) and docking model of reported monoamine neurotransmitters reuptake inhibitors. The compounds were synthesized in 3-simple steps and their biological activities were evaluated. Several compounds were proven to be potent inhibitors of serotonin and norepinephrine reuptake. Computer docking was performed to study the interaction of the most potent compound 35 with human serotonin transporter. The results of the analyses suggest that 4-arylpiperazine- and 4-benzylpiperidine naphthyl ethers might be promising antidepressants worthy of further studies.

Paudel|Suresh|S|
Min|Xiao|X|
Acharya|Srijan|S|
Khadka|Daulat Bikram|DB|
Yoon|Goon|G|
Kim|Kyeong-Man|KM|
Cheon|Seung Hoon|SH|

D050486:Serotonin Plasma Membrane Transport Proteins

D000068760:Serotonin and Noradrenaline Reuptake Inhibitors

4-Benzylpiperidine
Naphthyl ether
Docking
4-Arylpiperazine
Depression
Norepinephrine reuptake inhibitor
Serotonin reuptake inhibitor


Immunohistochemistry of the circadian clock in mouse and human vascular tissues.

Abstract:
Aim
The circadian clock is a molecular network that controls the body physiological rhythms. In blood vessels, the circadian clock components modulate vascular remodeling, blood pressure, and signaling. The goal in this study was to determine the pattern of expression of circadian clock proteins in the endothelium, smooth muscle, and adventitia of the vasculature of human and mouse tissues.

Methods
Immunohistochemistry was performed in frozen sections of mouse aorta, common carotid artery, femoral artery, lung, and heart at 12 AM and 12 PM for Bmal1, Clock, Npas2, Per and other clock components. Studies of expression were also assessed in human saphenous vein both by immunoblotting and immunohistochemistry.

Results
In this study, we identified the expression of Bmal1, Clock, Npas, Per1, Cry1, and accessory clock components by immunohistochemical staining in the endothelium, smooth muscle and adventitia of the mouse vasculature with differing temporal and cellular profiles depending on vasculature and tissue analyzed. The human saphenous vein also exhibited expression of clock genes that exhibited an oscillatory pattern in Bmal1 and Cry by immunoblotting.

Conclusion
These studies show that circadian clock components display differences in expression and localization throughout the cardiovascular system, which may confer nuances of circadian clock signaling in a cell-specific manner.

Anea|Ciprian B|CB|
Merloiu|Ana M|AM|
Fulton|David J R|DJR|
Patel|Vijay|V|
Rudic|R Dan|RD|

Clock
mouse
human
smooth muscle
aorta
Bmal1
Per
Cry
Circadian blood vessel
vascular endothelium


Intrinsic functional connectivity alterations in cognitively intact elderly APOE ε4 carriers measured by eigenvector centrality mapping are related to cognition and CSF biomarkers: a preliminary study.

Abstract: Apolipoprotein E (APOE) ε4 allele is the best established genetic risk factor for sporadic Alzheimer's disease (AD). However, there is a need to understand the effects of this genotype on the brain by simultaneously assessing intrinsic brain network and cerebral spinal fluid (CSF) biomarkers changes in healthy older ε4 carriers. Thirteen cognitively intact, elderly APOE ε4 carriers and 22 ε3 homozygotes were included in the present study. Eigenvector centrality mapping (ECM) was used to identify brain network hub organization based on resting-state functional MRI (rsfMRI). We evaluated comprehensive cognitive ability and tested levels of Aβ1-42, total-tau (t-tau) and phosphorylated-tau (p-tau181) in CSF. Comparisons of ECM between two groups were conducted, followed by correlations analyses between EC values with significant group differences and cognitive ability/CSF biomarkers. APOE ε4 carriers showed significantly decreased EC values in left medial temporal lobe (MTL), left lingual gyrus (LG) and increased EC values in left middle frontal gyrus (MFG) as compared to non-carriers. Correlation analysis demonstrated that left LG EC value correlated with Rey Auditory Verbal Learning Test total learning (RAVLT, r = 0.57, p < 0.05) and t-tau level (r = -0.57, p < 0.05), while left MFG EC values correlated with log-transformed Trail-Making Test B (TMT-B, r = -0.67, p < 0.05) in APOE ε4 carriers. This study suggests the APOE ε4 allele contributes to disruption of brain connectedness in certain functional nodes, which may result from neuronal death caused by toxicity of neurofibrillary tangles.

Functional connectivity
CSF
Apolipoproteins E
Alzheimer disease
Resting-state fMRI


Running economy, mechanics, and marathon racing shoes.

Abstract: The choice of marathon racing shoes can greatly affect performance. The purpose of this study is to metabolically and mechanically compare the consumer version of the Nike Vaporfly 4% shoe to two other popular marathon shoes, and determine differences in running economy. Nineteen subjects performed two 5-minute trials at 4.44m/s wearing the Adidas Adios Boost (AB), Nike Zoom Streak (ZS), and Nike Vaporfly 4% (VP) in random order. Oxygen uptake was recorded during minutes 3-5 and averaged across both shoe trials. On a second day, subjects wore reflective markers, and performed a 3-minute trial in each shoe. Motion and force data were collected over the final 30 seconds of each trial. VP oxygen uptake was 2.8% and 1.9% lower than the AB and ZS. Stride length, plantar flexion velocity, and center of mass vertical oscillation were significantly different in the VP. The percent benefit of the VP over AB shoe was predicted by subject ground time. These results indicate that use of the VP shoe results in improved running economy, partially due to differences in running mechanics. Subject variation in running economy improvement is only partially explained by variation in ground time.

Racing biomechanics energetics footwear kinematics kinetics


Disaggregating the impact of oil prices on European industrial equity indices: a spatial econometric analysis.

Abstract: This study investigates the relationship between daily returns of oil and ten European industrial equity indices for the period 2008-2017 using the spatial econometric technique. In our settings, the historical co-movements of sectoral returns are incorporated while modelling the contemporaneous relationships between oil and European sectoral returns. After controlling for regional and global equity risk factors, we find that oil returns pose a significantly positive effect on sectoral indices' returns in line with previous studies. However, the magnitude of economic impact found mostly by earlier studies was largely underestimated without considering the co-movements of sectoral indices. The use of spatial econometric technique allowed us to disaggregate the total impact into a direct (due to oil price) and an indirect (due to spillover effect because of intra-industry co-movements) effect of oil price changes. Our results indicate that the direct economic impact of changes in oil prices on industrial returns is almost 31% more than what has been found by earlier studies. The negative spatial dependence among sectoral indices provides a useful tool to identify the source of the indirect impact of oil on overall equity prices in Europe that in turn explains the overestimation of direct impact by 31%.

Hussain|Syed Mujahid|SM|
Naveed|Amjad|A|
Ahmed|Sheraz|S|
Ahmad|Nisar|N|

Oil prices
Spatial econometrics
Euro STOXX
European industrial indices


Early and Late Patient Outcomes in Urgent-Start Peritoneal Dialysis.

Abstract:
BACKGROUND
Significant interest in the practice of urgent-start peritoneal dialysis (PD) is mounting internationally, with several observational studies supporting the safety, efficacy, and feasibility of this approach. However, little is known about the early complication rates and long-term technique and peritonitis-free survival for patients who start PD urgently (i.e. within 2 weeks of catheter insertion), compared to those with a conventional start.

METHODS
This single-center, matched case-control study evaluated patients commencing PD between 2010 and 2015. Urgent-start PD patients were matched 1:3 with conventional-start PD controls based on diabetic status and age. The primary outcomes were early complications, both following catheter insertion and PD commencement (within 4 weeks). Secondary outcomes included technique and peritonitis-free survival.

RESULTS
A total of 104 patients (26 urgent-start, 78 conventional-start) were included. Urgent-start patients were more likely to be referred late, initiate PD in hospital, and be prescribed lower initial exchange volumes (p < 0.01). They experienced more frequent leaks post-catheter insertion (12% vs 1%, p = 0.047) and more frequent catheter migration following commencement of PD (12% vs 1%, p = 0.047). There were no significant differences in the rates of overall or infectious complications. Kaplan-Meier estimates of technique survival and time to first episode of peritonitis were comparable between the groups.

CONCLUSION
Compared with conventional-start PD, urgent-start PD has acceptably low early complication rates and similar long-term technique survival. Urgent-start PD appears to be a safe way to initiate urgent renal replacement therapy in patients without established dialysis access.

See|Emily J|EJ|
Cho|Yeoungjee|Y|
Hawley|Carmel M|CM|
Jaffrey|Lauren R|LR|
Johnson|David W|DW|

urgent-start
peritoneal dialysis
peritonitis
Complications
technique survival
end-stage kidney disease


Bioinspired Total Synthesis of the Dimeric Indole Alkaloid (+)-Haplophytine by Direct Coupling and Late-Stage Oxidative Rearrangement.

Abstract: A bioinspired convergent total synthesis of (+)-haplophytine, a dimeric indole alkaloid with diazabicyclo[3.3.1]nonane and hexacyclic aspidosperma segments, is described. This synthesis involves the direct coupling of the two segments in a AgNTf2 -mediated Friedel-Crafts reaction and construction of the diazabicyclo[3.3.1]nonane skeleton through late-stage chemoselective aerobic oxidation of the 1,2-diaminoethene moiety and a sequential semipinacol-type rearrangement.

Satoh|Hitoshi|H| Ojima|Ken-Ichi|KI| Ueda|Hirofumi|H| Tokuyama|Hidetoshi|H|

total synthesis
alkaloids
oxidation
rearrangement
Friedel-Crafts reaction


Endovascular treatment of femoro-popliteal lesions.

Abstract: Peripheral artery disease (PAD) is a major health concern affecting more than 200 million people worldwide and studies have shown PAD to be a strong predictor of mortality, morbidity, and disability. The management of PAD is multi-tiered and advancements in technology have given physicians more options for endovascular revascularization if medical therapy does not result in substantial improvement. Many randomized controlled trials have reported efficacy of various therapies including laser atherectomy, stent technology, and drug-coated balloons over standard percutaneous transluminal angioplasty; however, uncertainty regarding the best standard of care remains unclear because of a lack of head to head comparisons between novel therapies. Furthermore, variability in the reported clinical outcomes exists and makes it difficult to evaluate the superiority of any specific treatment modality, especially for functional capacity and quality of life. Recently established consensus definitions for clinical outcomes coupled with investigators incorporating direct comparisons within clinical trials will be crucial to establish consistent care and meaningful gain in treatment for these patients. This review will highlight the treatment modalities, literature supporting each treatment modality, and insight into why they are being used and why variation exists around the United States.

D000792:Angiography
D057510:Endovascular Procedures
D005263:Femoral Artery
D006801:Humans
D058729:Peripheral Arterial Disease
D011150:Popliteal Artery
D014654:Vascular Patency

peripheral artery disease
revascularization
atherectomy
stent
balloon
angioplasty


3-O-Methyl-D-glucose mutarotation and proton exchange rates assessed by 13C, 1H NMR and by chemical exchange saturation transfer and spin lock measurements.

Abstract: 3-O-Methyl-D-glucose (3OMG) was recently suggested as an agent to image tumors using chemical exchange saturation transfer (CEST) MRI. To characterize the properties of 3OMG in solution, the anomeric equilibrium and the mutarotation rates of 3OMG were studied by 1H and 13C NMR. This information is essential in designing the in vivo CEST experiments. At room temperature, the ratio of α and β 3OMG anomers at equilibrium was 1:1.4, and the time to reach 95% equilibrium was 6 h. The chemical exchange rates between the hydroxyl protons of 3OMG and water, measured by CEST and spin lock at pH 6.14 and a temperature of 4 °C, were in the range of 360-670 s-1.

Chemical exchange saturation transfer (CEST)


SPIO-loaded nanostructured lipid carriers as liver-targeted molecular T2-weighted MRI contrast agent.

Abstract:
Background
Superparamagnetic iron oxide (SPIO) acts as a negative contrast agent in magnetic resonance imaging (MRI), and is widely used in clinical applications, including the diagnosis of hepatic diseases. Hepatocyte-targeted magnetic resonance contrast agents (MRCAs) can provide useful information for evaluating hepatic diseases. We prepared targeted magnetic nanostructured lipid carriers (MNLCs) to enhance the hepatocytes targeting efficiency.

Methods
In vitro characterizations of MNLCs were determined by transmission electron microscopy (TEM). The cytotoxicity assay of the MNLCs was measured by methyl tetrazolium (MTT) method. The uptaken study was measured by confocal microscopy, flow cytometry and MRI in vitro. The enhanced liver-targeting efficiency of MNLCs was measured by fluorescence imaging and MRI in vivo.

Results
Gal-NLC-SPIO was prepared successfully. The cytotoxicity assay of the MNLCs demonstrated that the MNLC had relatively low cytotoxicity and high biocompatibility for LO2 cells. More importantly, we confirmed that Gal-NLC-SPIO had greater uptake by LO2 cells than Gal-NLC-SPIO/PEG and free Gal in vitro. A liver distribution study of MNLCs in normal mice demonstrated that the fluorescent signal values to livers of the Gal-NLC-SPIO were signiﬁcantly stronger than those of NLC-SPIO and Gal-NLC-SPIO/PEG. The liver targeting efficiency of Gal-NLC-SPIO was confirmed both in vitro and in vivo.

Conclusions
We successfully developed liver-targeting MNLCs, which showed accurate hepatocytes targeting, and thus have the potential to be a new MRI contrast agent to help the diagnosis of liver diseases.

Zhu|Xiuliang|X| Deng|Xueying|X| Lu|Chenying|C| Chen|Ying|Y| Jie|Liyong|L| Zhang|Qian|Q| Li|Wei|W| Wang|Zuhua|Z| Du|Yongzhong|Y| Yu|Risheng|R|

solid lipid nanoparticle galactose (SLN galactose)


Safety and efficacy of bone marrow-derived cells therapy on cardiomyopathy: a meta-analysis.

Abstract:
BACKGROUND
Controversial results still existed on the clinical utility of bone marrow-derived cells (BMCs) for cardiomyopathy (CMP). This study aims to reveal the true power of this promising approach by synthesizing all the available data on this subject matter.

METHODS
Twenty studies including 1418 patients were identified from systematic search. Weighted mean differences for changes in left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), 6-min walk distance, and NYHA functional class were estimated with a random-effects model. Major adverse cardiovascular event (MACE), rehospitalization, all-cause mortality, and patients' quality of life were also calculated.

RESULTS
Compared with the control group, BMC therapy resulted in greater LVEF (3.72%, 95% CI 2.31 to 5.13, P < 0.0001), 6-min walk distance (53.16, 95% CI 25.17 to 81.10, P = 0.0002), NYHA functional class (- 0.48, 95% CI - 0.65 to - 0.31, P < 0.0001), and smaller LVESV (- 16.79, 95% CI - 27.21 to - 6.38, P = 0.002). BMC treatment significantly reduced the mortality rate and improved patients' quality of life. No significant difference was found between the BMCs and control group in LVEDV, MACE, and rehospitalization rate. However, the outcomes showed a clear trend in favor of the BMC group. Subgroup analysis showed that LVEF improved greater in a subgroup of intracoronary infusion, BMSC, or higher cell dose.

CONCLUSION
The results of the current meta-analysis suggest that BMC treatment for CMP is safe and feasible. This therapy was associated with persistent improvements in LV function, LV remodeling, functional class, patients' survival, and quality of life. Intracoronary infusion of high-dose (> 108) BMSC might be a better therapeutic option for CMP patients. Further evidences are needed to verify our results.

Wang|Chao|C|0000-0001-5848-2311 Li|Jingzhao|J| Zhang|Boya|B| Li|Yongjian|Y|

Cardiomyopathy
Bone marrow cells
Ventricular function
Ventricular remodeling


Quantitative proteomic analysis of deer antler stem cells as a model of mammalian organ regeneration.

Abstract: The ability to activate and regulate stem cells during wound healing and tissue/organ regeneration is a promising field which could bring innovative approaches to regenerative medicine. The regenerative capacity of invertebrates has been well documented, however in mammals, stem cells that drive organ regeneration are rare. Deer antler is unique in providing a mammalian model of complete organ regeneration based on stem cells. The present study investigated the differentially regulated proteins (DRPs) between different antler stem cell populations (n = 3) using 2D-DIGE. Western blotting was used to validate the proteomics results. Comparative proteomics resulted in protein profiles which were similar for the biological replicates but different between the cells derived from two different stem cell niches involved in antler growth/regeneration and cells derived from facial periosteum. Ninety-two up- and down-regulated proteins were identified by MALDI-TOF MS. The work indicates that the epithelial-mesenchymal transition process may participate in the initiation of antler regeneration including the first stage of scar-less wound healing. Cell mobility is also highly regulated during antler regeneration. Energy and nucleotide metabolism may however be less active in antler regeneration as compared to that in antler generation phase. These results provide new insights into the underlying mechanisms of stem cell-based regeneration of mammalian organs.

Dong|Zhen|Z| Coates|Dawn|D| Liu|Qingxiu|Q| Sun|Hongmei|H| Li|Chunyi|C|

Proteomics
Deer
Antler stem cell
Regenerative medicine
2D-DIGE
Periosteum


Overexpression of the long noncoding RNA TRHDE-AS1 inhibits the progression of lung cancer via the miRNA-103/KLF4 axis.

Abstract:
AIM
The aim of this study was to explore the role and molecular basis of the long noncoding RNA (lncRNA) TRHDE-AS1 in lung cancer.

METHODS
We used real-time polymerase chain reaction to analyze the messenger RNA expression levels of TRHDE-AS1, miR-103, and KLF4. The cell viability, proliferation, and invasion rates were assessed via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, Cell Counting Kit-8, and Transwell assays to elucidate the role of TRHDE-AS1.

RESULTS
Our results demonstrated that the lncRNA TRHDE-AS1 is mainly located in the cytoplasm and that the cell proliferation and invasion were suppressed in the group of overexpressed TRHDE-AS1. We also showed that miR-103 could directly bind to TRHDE-AS1 and provided evidence of the oncogenic function of miR-103. Besides, we proved that miR-103 exerted its function by adjusting the expression level of the tumor-suppressor gene KLF4, and the expression level was negatively associated with miR-103.

CONCLUSION
In summary, we determined that the effects of TRHDE-AS1 on proliferation, invasion, and cell death could be rescued by the overexpression of miR-103. Our experiments demonstrate that the TRHDE-AS1/miR-103/KLF4 axis may provide new evidence for understanding the molecular basis of lung cancer.

Zhuan|Bing|B| Lu|Yuting|Y| Chen|Qian|Q| Zhao|Xia|X| Li|Ping|P| Yuan|Qun|Q| Yang|Zhao|Z|0000-0002-8081-8253

D023041:Xenograft Model Antitumor Assays


Developmental scRNAseq Trajectories in Gene- and Cell-State Space-The Flatworm Example.

Abstract: Single-cell RNA sequencing has become a standard technique to characterize tissue development. Hereby, cross-sectional snapshots of the diversity of cell transcriptomes were transformed into (pseudo-) longitudinal trajectories of cell differentiation using computational methods, which are based on similarity measures distinguishing cell phenotypes. Cell development is driven by alterations of transcriptional programs e.g., by differentiation from stem cells into various tissues or by adapting to micro-environmental requirements. We here complement developmental trajectories in cell-state space by trajectories in gene-state space to more clearly address this latter aspect. Such trajectories can be generated using self-organizing maps machine learning. The method transforms multidimensional gene expression patterns into two dimensional data landscapes, which resemble the metaphoric Waddington epigenetic landscape. Trajectories in this landscape visualize transcriptional programs passed by cells along their developmental paths from stem cells to differentiated tissues. In addition, we generated developmental "vector fields" using RNA-velocities to forecast changes of RNA abundance in the expression landscapes. We applied the method to tissue development of planarian as an illustrative example. Gene-state space trajectories complement our data portrayal approach by (pseudo-)temporal information about changing transcriptional programs of the cells. Future applications can be seen in the fields of tissue and cell differentiation, ageing and tumor progression and also, using other data types such as genome, methylome, and also clinical and epidemiological phenotype data.

D018507:Gene Expression Regulation, Developmental

self-organizing maps
machine learning
planarian
differentiation of tissues
pseudotime trajectories
single cell RNA sequencing
transcriptomic landscapes


Comparison of Birth Outcomes by Gestational Diabetes Screening Criteria.

Abstract: Objectives  This study is to examine the association between different diagnostic criteria for gestational diabetes mellitus (GDM) and adverse birth outcomes. Study Design  A retrospective cohort study of 5,937 women with a singleton pregnancy was conducted, who completed GDM screening between 24 to 32 weeks gestational age. Four nonoverlapping groups of women defined as: 1) Normal: glucose challenge test (GCT) <130 mg/dL, 2) elevated GCT + normal oral glucose tolerance test (OGTT): abnormal 1 hour GCT + normal 3 hour OGTT, 3) GDM/International Association of Diabetes in Pregnancy Study Group (IADPSG): abnormal 3 hour OGTT by the IADPSG criteria, and 4) GDM/Carpenter-Coustan (CC): diagnosis per CC criteria. We used logistic regression to examine the association between GDM group classification and main outcome of macrosomia and secondary birth outcomes. Results  Prevalences were GDM/CC 4.6%, GDM/IADPSG 3.0, and 7.6% overall. GDM/IADPSG group was associated with increased macrosomia (adj OR [odd ratio] 1.87; 95% CI [confidence interval]: 1.08-3.25; p  = 0.02), while GDM/CC group was associated with increased preterm birth (adj OR 1.75; 95% CI: 1.05-2.80; p  = 0.03). Conclusion  Little difference in birth outcomes was found between the two criteria, GDM/CC and GDM/IADPSG. Randomized controlled trials are needed to clarify the risks and benefits of these screening paradigms before their incorporation into clinical practice.

Davis|Esa M|EM|
Scifres|Christina M|CM|
Abebe|Kaleab|K|
Costacou|Tina|T|
Comer|Diane|D|
Catalano|Patrick|P|
Simhan|Hyagriv|H|
Freiberg|Matthew|M|
Day|Nancy|N|

gestational diabetes
fetal growth
pregnancy outcomes
screening strategies


Two new species of <i>Sphaeronemoura</i> (Plecoptera: Nemouridae) from Oriental China.

Abstract: Two new species of the genus Sphaeronemoura of the stonefly family Nemouridae, S. asymmetria sp. n. from Guizhou Province and S. hainana sp. n. from Hainan Province, respectively, are described from China. These findings represent the first record of the genus from these two provinces. Their relationships with other species from adjacent regions are discussed. With the new species described herein, 16 species of Sphaeronemoura are now known.

Plecoptera, China, Sphaeronemoura, new species


Chronic nicotine activates stress/reward-related brain regions and facilitates the transition to compulsive alcohol drinking.

Abstract: Alcohol and nicotine are the two most co-abused drugs in the world. Previous studies have shown that nicotine can increase alcohol drinking in nondependent rats, yet it is unknown whether nicotine facilitates the transition to alcohol dependence. We tested the hypothesis that chronic nicotine will speed up the escalation of alcohol drinking in rats and that this effect will be accompanied by activation of sparsely distributed neurons (neuronal ensembles) throughout the brain that are specifically recruited by the combination of nicotine and alcohol. Rats were trained to respond for alcohol and made dependent using chronic, intermittent exposure to alcohol vapor, while receiving daily nicotine (0.8 mg/kg) injections. Identification of neuronal ensembles was performed after the last operant session, using immunohistochemistry. Nicotine produced an early escalation of alcohol drinking associated with compulsive alcohol drinking in dependent, but not in nondependent rats (air exposed), as measured by increased progressive-ratio responding and increased responding despite adverse consequences. The combination of nicotine and alcohol produced the recruitment of discrete and phenotype-specific neuronal ensembles (∼4-13% of total neuronal population) in the nucleus accumbens core, dorsomedial prefrontal cortex, central nucleus of the amygdala, bed nucleus of stria terminalis, and posterior ventral tegmental area. Blockade of nicotinic receptors using mecamylamine (1 mg/kg) prevented both the behavioral and neuronal effects of nicotine in dependent rats. These results demonstrate that nicotine and activation of nicotinic receptors are critical factors in the development of alcohol dependence through the dysregulation of a set of interconnected neuronal ensembles throughout the brain.

D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2

D002492:Central Nervous System Depressants

compulsivity
alcohol
neuronal ensembles
Fos
addiction
tobacco


Side-Effects of Glyphosate to the Parasitoid Telenomus remus Nixon (Hymenoptera: Platygastridae).

Abstract: The aim of this study was to compare the side-effects of glyphosate to the parasitoid Telenomus remus Nixon (Hymenoptera: Platygastridae) when parasitoids were exposed to this chemical at the pupal (inside host eggs) and adult stages. Bioassays were conducted under laboratory conditions according to the International Organization for Biological Control (IOBC) standard methods for testing side-effects of pesticides to egg parasitoids. Different glyphosate-based pesticides (Roundup Original®, Roundup Ready®, Roundup Transorb®, Roundup WG®, and Zapp Qi®) were tested at the same acid equivalent concentration. Treatments were classified following the IOBC toxicity categories as (1) harmless, (2) slightly harmful, (3) moderately harmful, and (4) harmful. When tested against T. remus adults, Roundup Original®, Roundup Ready®, Roundup Transorb®, and Roundup WG® reduced parasitism 2 days after parasitoid emergence, being classified as slightly harmful. Differently, when tested against T. remus pupae, all tested glyphosate-based products did not differ in their lethal effect and therefore did not reduce T. remus adult emergence or parasitism capacity, being classified as harmless. However, differences on sublethal toxicity were found. Parasitism of individuals emerging from parasitized eggs sprayed at the pupal stage of T. remus with Zapp Qi® was lower compared to control, but parasitism was still higher than 66%, and therefore, Zapp Qi® was still classified as harmless. In conclusion, all tested glyphosate-based products can be used in agriculture without negative impact to T. remus as none was classified as harmful or moderately harmful to this parasitoid when exposure occurred at the pupal or adult stages.

Stecca|C S|CS|
Bueno|A F|AF|
Pasini|A|A|
Silva|D M|DM|
Andrade|K|K|
Filho|D M Z|DM|

Biological control
herbicide
integrated pest management
sustainable pest management
transgenerational effects


Therapeutic properties in Tunisian hot springs: first evidence of phenolic compounds in the cyanobacterium Leptolyngbya sp. biomass, capsular polysaccharides and releasing polysaccharides.

Abstract:
BACKGROUND
In Tunisia, the use of hot spring waters for both health and recreation is a tradition dating back to Roman times. In fact, thermal baths, usually called "Hammam" are recommended as a therapeutic and prophylactic measure against many types of illness and toxicity. While the chemical concentration of thermal water is admittedly associated with its therapeutic effects, the inclusion in spa waters of efficient bioproduct additives produced by photosynthetic microorganisms and that act against oxidative stress may comprise a significant supplementary value for thermal centers. The aim of this study was to investigate the antioxidant potential of the Tunisian thermophilic cyanobacterium Leptolyngbya sp. and to determine its phytochemical constituents and phenolic profile.

METHODS
BME (Biomass Methanolic Extract), CME (Capsular polysaccharides Methanolic Extract) and RME (Releasing polysaccharides Methanolic Extract) of Leptolyngbya sp. were examined for their antioxidant activities by means of DPPH, hydroxyl radical scavenging and ferrous ion chelating assays. Their total phenols, flavonoids, carotenoids, Mycosporine-like amino acids (MAAs) and vitamin C contents, as well as their phenolic profiles were also determined.

RESULTS
BME has the highest content of phenols (139 ± 1.2 mg/g), flavonoids (34.9 ± 0.32 mg CEQ/g), carotenoids (2.03 ± 0.56 mg/g) and vitamin C (15.7 ± 1.55 mg/g), while the highest MAAs content (0.42 ± 0.03 mg/g) was observed in CME. BME presented both the highest DPPH and hydroxyl radical scavenging ability with an IC50 of 0.07 and 0.38 mg/ml, respectively. The highest ferrous chelating capacity was detected in CME with an IC50 = 0.59 mg/ml. Phenolic profiles revealed the presence of 25 phenolic compounds with the existence of hydroxytyrosol, oleuropein, resveratrol and pinoresinol.

CONCLUSION
The study demonstrated that the cyanobacterium Leptolyngbya sp. possesses abundant natural antioxidant products which may have prophylactic and therapeutic effects on many types of illness and toxicity. The present findings not only explain and reinforce the rationale behind traditional therapeutic practices in Tunisia in the exploitation of the country's hot springs, but support the addition of Leptolyngbya to thermal waters as a means to enhance the value and reputation of the curative nature of Tunisian thermal waters.

Trabelsi|Lamia|L|
Mnari|Amira|A|
Abdel-Daim|Mohamed M|MM|
Abid-Essafi|Salwa|S|
Aleya|Lotfi|L|

D002851:Chromatography, High Pressure Liquid

Leptolyngbya sp.
Hot spring water
Phenolic profile
Antioxidant activities
Phytochemical content


Modification of nanocellulose by poly-lysine can inhibit the effect of fumonisin B1 on mouse liver cells.

Abstract: Fumonisin B1 is an important mycotoxin, mainly produced by Fusarium verticillioides. It has toxic effects on liver, brain, and kidney cells. The first aim of this study was to synthesize nanocellulose modified with poly-lysine (NMPL), and the second aim was to evaluate the adsorption of fumonisin B1 by NMPL. As third aim, the function of mouse liver cells was investigated after exposure to fumonisin B1, and fumonisin B1+ NMPL. In this study, NMPL was prepared using cross-linker, and then incubated with fumonisin B1 at controlled conditions. After incubation, the adsorption and release of fumonisin B1 were evaluated in each condition. Next, mouse liver cells were separately exposed to fumonisin B1, NMPL, and (fumonisin B1+NMPL). Then, the level of aniline aminotransferase (ALT) and aspartate aminotransferase (AST) was evaluated. It was found that both adsorption and release of fumonisin B1 were not affected by temperature and incubation time, but affected by pH and concentration of NMPL. Also, this study showed NMPL could adsorb fumonisin B1 in different foodstuffs. Importantly, although the levels of ALT and AST were increased when the cells were treated with fumonisin B1 alone, they were not affected when exposed to NMPL or (fumonisin B1+NMPL). The authors suggest that NMPL is a good adsorbent to remove and inhibit fumonisin B1.

Jebali|Ali|A|
Yasini Ardakani|Seyed Ali|SA|
Shahdadi|Hossein|H|
Balal Zadeh|Mohammad Hossein|MH|
Hekmatimoghaddam|Seyedhossein|S|

Nanocellulose
Poly-lysine
Fumonisin B1
Liver
Adsorption


Impact of a single treatment of injectable doramectin on weight gain post weaning in beef heifers and steers in central Queensland, Australia.

Abstract:
OBJECTIVES
To demonstrate the impact of a single drench with a label dose of injectable doramectin subsequent to weaning on the growth and performance of heifers and steers in central Queensland beef herds.

METHODS
Three studies were undertaken on recently-weaned Bos indicus-cross beef calves with ≥ 75% B. indicus content on two farms in central Queensland, just north of the Tropic of Capricorn. Farm 1 was located 50 km north and Farm 2 75 km north-west of Rockhampton. In each study, half of a group of recently-weaned beef calves were treated by random allocation with 0.2 mg/kg of injectable doramectin, and the remainder acting as untreated controls. Study 1 (Farm 1) enrolled 250 heifers, while studies 2 and 3 (Farm 2) both enrolled 200 steers and 200 heifers. The farms involved did not historically use macrocyclic lactone-based drenches on their cattle. There were varying periods of follow-up, with treated and control cattle pastured as one group throughout the study period. Worm burdens were monitored using standard faecal egg counts and larval differentiation procedures. In all studies, the worm genera present were a mix of Cooperia spp., Haemonchus spp. and Oesophagostomum spp.

RESULTS
In study 1, conducted on Farm 1 beginning 9 July 2012, doramectin-treated cattle gained an average of 0.27 kg/day while control cattle gained 0.19 kg/day over a monitoring period of 121 days (P < 0.0001). In study 2, conducted on Farm 2 beginning 28 July 2015, doramectin-treated cattle gained an average of 0.15 kg/day versus 0.145 kg/day in the control group (P = 0.44) over a 231-day study period. In study 3, conducted on Farm 2 beginning 4 August 2016, doramectin-treated steers and heifers gained an average of 0.431 and 0.402 kg/day versus 0.342 and 0.311 kg/day in the control group, respectively, over the first 91 days of the study (P < 0.0001 in both cases). The differences in average daily gain (ADG) in subsequent time periods were not statistically significant for steers or heifers. However, overall differences in ADG from day 0 remained statistically significant out to day 258, when the study ended for the heifers. By day 594, when the study ended for the steers, the difference in ADG was no longer significant.

CONCLUSION
Treatment with injectable doramectin soon after weaning resulted in improved weight gain in the 3 months after weaning in two of the three studies.

doramectin
weight gain
weaning
drenching
cattle
anthelmintics
macrocyclic lactones


Reversal of stage 5 chronic kidney disease by aortic valve replacement in kidney transplant recipient: a case report.

Abstract:
BACKGROUND
Cardiorenal syndrome (CRS) is a group of pathophysiological disorders affecting heart and kidneys.

CASE PRESENTATION
We present 44-year-old kidney transplant recipient with acute-on-chronic graft failure in the course of CRS due to acutely decompensated heart failure associated with severe aortic regurgitation successfully treated with aortic valve replacement. Because of graft failure progression and difficult to eradicate infections he was treated with dialysis and radical minimization of immunosuppression. After 74 days of renal replacement therapy the patient regained graft function after successful aortic valve replacement. The dialysis could be stopped and immunosuppressive therapy was reintroduced. Heart and renal function are stable and patient is doing well without dialysis for 3 years.

CONCLUSIONS
The return of kidney graft function can occur even after a long period of dialysis therapy due to improved cardiovascular function. Therefore, distinguishing an acute-on-chronic CRS subtype is mandatory to enable specific patient approach.

Hryniewiecka|E|E| Hryniewiecki|T|T| Różański|J|J| Pilecki|T|T| Zagożdżon|R|R| Orłowski|T|T| Gołębiowski|M|M| Pączek|L|L| Mucha|K|K| Foroncewicz|B|B|0000-0002-0757-4547

D019918:Heart Valve Prosthesis Implantation

Aortic valve replacement
Kidney transplantation
Cardiorenal syndrome
Acute-on-chronic
Heart failure
Aortic insufficiency
End stage renal disease
Haemodialysis


Simultaneous measurement of epinastine and its metabolite, 9,13b-dehydroepinastine, in human plasma by a newly developed ultra-performance liquid chromatography-tandem mass spectrometry and its application to pharmacokinetic studies.

Abstract: Epinastine is an antiallergic drug with high selectivity for histamine receptors. It has been reported that 9,13b-dehydroepinastine is present as a metabolite in vivo in humans, but there was little information about their pharmacokinetics (PKs) in humans. Although several analytical methods have been reported for epinastine analysis in different matrices, none are available for its metabolite. Therefore, the purpose of this study was to develop an analytical method to simultaneously measure epinastine and its metabolite, 9,13b-dehydroepinastine, in human plasma samples using an ultra-performance liquid chromatography-tandem mass spectrometer. Analytes were separated on a C18 column. Quantification of this analysis was performed on a triple-quadrupole mass spectrometer. Chromatograms showed high sensitivity, selectivity, and resolution with no interference with plasma constituents. Calibration curves for both epinastine and 9,13b-dehydroepinastine in human plasma were 0.1-50 ng/ml and displayed excellent linearity with correlation coefficients (r2 ) >0.99. The developed analytical method satisfied the criteria of international guidance and was validated. The method could be successfully applied to pharmacokinetic studies of epinastine and, for the first time, the metabolite kinetics of epinastine to 9,13b-dehydroepinastine in humans after oral administration of 20 mg epinastine hydrochloride tablets. Our study is expected to be useful in future studies such as dosage settings and clinical pharmacotherapy.


A Curriculum to Improve Pediatric Residents' Telephone Triage Skills.

Abstract:
Introduction
Telephone triage systems are frequently used due to their success in decreasing emergency department utilization, reduction of health care costs, and high levels of satisfaction among patients and providers. Despite phone triage's prevalence, few residency programs have designated curricula for residents to learn this vital skill.

Methods
We designed a phone triage curriculum initially piloted with senior residents at one of our continuity clinics. The curriculum consisted of a didactic session, a just-in-time simulation training session, and an experiential component of being on call during the ambulatory rotation. Retrospective pre-post self-assessments evaluated resident perceptions of their skills in taking histories and triaging care over the phone in addition to obtaining qualitative feedback from faculty and residents immediately after the curriculum and 1-2 years postgraduation.

Results
Of 11 eligible residents, 10 (91%) chose to participate in the pilot curriculum. Residents reported that their skills in history taking over the phone improved from 20% to 90% and their ability to triage patients over the phone improved from 0% to 80%. This led to a quality improvement initiative to increase patient calls and has continued for 5 years, with continued positive feedback from residents and attendings.

Discussion
Phone triage skills are a necessity for pediatric providers, but few residency programs have training curricula in place. Through an experience-based phone triage program, residents significantly improved their self-reported skills at history taking and triaging. Similar curricula could easily be adopted at other institutions.

Roth|Lauren T|LT|0000-0001-5592-3927
Lane|Mariellen|M|
Friedman|Suzanne|S|

Pediatrics
Phone Triage
Case-Based Learning
Clinical/Procedural Skills Training
Resident Education


Transforming growth factor-β signaling is upregulated in sporadic inclusion body myositis.

Abstract:
INTRODUCTION
In this study we aimed to determine whether transforming growth factor-β (TGF-β) signaling is dysregulated in sporadic inclusion body myositis (sIBM) muscle samples.

METHODS
We examined TGF-β signaling markers in muscle samples from 24 sIBM patients and compared them with those from 10 dermatomyositis (DM) patients using immunohistochemistry and Western blot analyses.

RESULTS
Compared with the DM muscle fibers, the sIBM muscle fibers exhibited greater TGF-β, TGF-β receptor type I (TβRI), and TGF-β receptor type II (TβRII) immunoreactivity in the cytoplasm, as well as greater phosphorylated Smad2 (pSmad2) immunoreactivity in the myonuclei. The signal intensities of TGF-β, TβRI, and TβRII immunoreactivity correlated significantly with muscle fiber cross-sectional areas. Western blot analyses indicated higher expression levels of TGF-β, TβRI, TβRII, and pSmad2 in the sIBM muscle samples than in the DM muscle samples.

CONCLUSIONS
These data indicate that upregulation of TGF-β signaling may be an important molecular event in sIBM. Muscle Nerve 55: 741-747, 2017.

Noda|Seiya|S| Koike|Haruki|H| Maeshima|Shinya|S| Nakanishi|Hirotaka|H| Iijima|Masahiro|M| Matsuo|Koji|K| Kimura|Seigo|S| Katsuno|Masahisa|M| Sobue|Gen|G|

D000077293:Receptor, Transforming Growth Factor-beta Type I

D000077294:Receptor, Transforming Growth Factor-beta Type II

D018125:Receptors, Transforming Growth Factor beta

transforming growth factor-β
signaling
sporadic inclusion body myositis
dermatomyositis
phosphorylated Smad2
degenerative disease
inflammatory myopathy


Small cyclic sodium channel inhibitors.

Abstract: Voltage-gated sodium (NaV) channels play crucial roles in a range of (patho)physiological processes. Much interest has arisen within the pharmaceutical industry to pursue these channels as analgesic targets following overwhelming evidence that NaV channel subtypes NaV1.7-NaV1.9 are involved in nociception. More recently, NaV1.1, NaV1.3 and NaV1.6 have also been identified to be involved in pain pathways. Venom-derived disulfide-rich peptide toxins, isolated from spiders and cone snails, have been used extensively as probes to investigate these channels and have attracted much interest as drug leads. However, few peptide-based leads have made it as drugs due to unfavourable physiochemical attributes including poor in vivo pharmacokinetics and limited oral bioavailability. The present work aims to bridge the gap in the development pipeline between drug leads and drug candidates by downsizing these larger venom-derived NaV inhibitors into smaller, more "drug-like" molecules. Here, we use molecular engineering of small cyclic peptides to aid in the determination of what drives subtype selectivity and molecular interactions of these downsized inhibitors across NaV subtypes. We designed a series of small, stable and novel NaV probes displaying NaV subtype selectivity and potency in vitro coupled with potent in vivo analgesic activity, involving yet to be elucidated analgesic pathways in addition to NaV subtype modulation.

Peigneur|Steve|S|
da Costa Oliveira|Cristina|C|
de Sousa Fonseca|Flávia Cristina|FC|
McMahon|Kirsten L|KL|
Mueller|Alexander|A|
Cheneval|Olivier|O|
Cristina Nogueira Freitas|Ana|A|
Starobova|Hana|H|
Dimitri Gama Duarte|Igor|I|
Craik|David J|DJ|
Vetter|Irina|I|
de Lima|Maria Elena|ME|
Schroeder|Christina I|CI|
Tytgat|Jan|J|

D061567:Voltage-Gated Sodium Channel Blockers

Nociception
Pain
Cyclic peptide
Cone snail toxin
Spider toxin
Voltage gated sodium channel


Resveratrol protects against atherosclerosis, but does not add to the antiatherogenic effect of atorvastatin, in APOE*3-Leiden.CETP mice.

Abstract: Resveratrol is a major constituent of traditional Asian medicinal herbs and red wine and is suggested to be a potential antiatherosclerotic drug due to its proposed hypolipidemic, anti-inflammatory and antioxidative properties. The aim of this study was to evaluate whether resveratrol protects against atherosclerosis development in APOE*3-Leiden.CETP (E3L.CETP) mice and adds to the antiatherogenic effect of mild statin treatment, currently the most widely used antiatherogenic therapy. E3L.CETP mice were fed a cholesterol-rich diet without (control) or with resveratrol (0.01% w/w), atorvastatin (0.0027% w/w) or both for 14 weeks. During the study plasma lipid, inflammatory and oxidative stress parameters were determined. Resveratrol reduced atherosclerotic lesion area (-52%) in the aortic root, comparable to atorvastatin (-40%) and the combination of both drugs (-47%). The collagen/macrophage ratio in the atherosclerotic lesion, a marker of plaque stability, was increased by resveratrol (+108%), atorvastatin (+124%) and the combination (+154%). Resveratrol decreased plasma cholesterol levels (-19%) comparable to atorvastatin (-19%) and the combination (-22%), which was completely confined to (very)low-density lipoprotein cholesterol levels in all groups. Post hoc analyses showed that the antiatherogenic effect of atorvastatin could be explained by cholesterol lowering, while the antiatherosclerotic effect of resveratrol could be attributed to factors additional to cholesterol lowering. Markers of inflammation and oxidative stress were not different, but resveratrol improved macrophage function. We conclude that resveratrol potently reduces atherosclerosis development and induces a more stable lesion phenotype in E3L.CETP mice. However, under the experimental conditions tested, resveratrol does not add to the antiatherogenic effect of atorvastatin.

Berbée|Jimmy F P|JF|
Wong|Man C|MC|
Wang|Yanan|Y|
van der Hoorn|José W A|JW|
Khedoe|Padmini P S J|PP|
van Klinken|Jan B|JB|
Mol|Isabel M|IM|
Hiemstra|Pieter S|PS|
Tsikas|Dimitrios|D|
Romijn|Johannes A|JA|
Havekes|Louis M|LM|
Princen|Hans M G|HM|
Rensen|Patrick C N|PC|

3-hydroxy-3-methylglutaryl coenzyme A reductase

cholesteryl ester transfer protein cox1/-2, cyclooxygenase-1/-2

lectin-like oxidized low-density lipoprotein receptor-1

P P P P P P P M M M U U U U U U U U U U U M M M U U M M U U U U U U M U U U U U U U


Study on the durability of concrete with FNS fine aggregate.

Abstract: As a by-product of nickel production, the ferronickel slag (FNS) puts a lot of pressure on the environment. It is becoming more and more urgent to deal with the increasing FNS. The aim of this study is to explore the durability of concrete with FNS fine aggregate. Two kinds of FNS with different storage time were selected. The radioactivity detection, XRD test and stability detection of FNS were conducted to ensure FNS can be used as construction materials. Then the durability of concrete with 13%, 27%, 40% and 50% FNS (by weight of fine aggregate) was investigated, respectively. It was found that the properties of concrete prepared from FNS with different storage time had little difference. The results indicated that 27% FNS replacement showed improvement in resistance to sulfate attack by 22% but the resistance to chloride ion penetration was not significantly influenced. Moreover, 40% FNS addition brought a 33% abrasion reduction than that of original concrete. SEM analysis showed that FNS produced more C-S-H gels and improved the microstructure of concrete. This study indicated that proper content of FNS can be used as fine aggregate and it was beneficial to the durability of concrete, especially to the abrasion resistance.

Liu|Xiaoming|X| Li|Tingyu|T| Tian|Weiguang|W| Wang|Yiqun|Y| Chen|Yanhu|Y|

Durability
Concrete
FNS
Fine aggregate
Radioactivity


Comparative effects of immediate-release and extended-release aspirin on basal and bradykinin-stimulated excretion of thromboxane and prostacyclin metabolites.

Abstract: A goal of aspirin therapy is to inhibit thromboxane production and platelet aggregation without inhibiting endothelial production of the vasodilator and anti-thrombotic prostacyclin. This study tested the hypothesis that extended-release aspirin (NHP-554C) would have increased selectivity for inhibition of basal and simulated thromboxane formation compared to immediate-release aspirin (ASA). Thirty-six healthy subjects were randomized to NHP-554C or ASA groups. Within each group, subjects were randomized to 5-day treatment with 81 mg/d, 162.5 mg/d and placebo in a crossover design in which treatment periods were separated by 2-week washout. On the fifth day of treatment, 81 mg/d and 162.5 mg/d ASA reduced basal urinary excretion of the stable thromboxane metabolite 11-dehydro-thromboxane B2 62.3% and 66.2% and basal excretion of the stable prostacyclin metabolite 2,3-dinor-6-keto-PGF1α 22.8% and 26.5%, respectively, compared to placebo. NHP-554C 81 mg/d and 162.5 mg/d reduced 11-dehydro-thromboxane B2 53% (P = 0.03 vs. ASA 81 mg/d) and 67.9% and 2,3-dinor-6-keto-PGF1α 13.4% and 18.5%, respectively. NHP-554C 81 mg/d did not significantly reduce basal excretion of the prostacyclin metabolite. Both doses of ASA and NHP significantly reduced excretion of both thromboxane and prostacyclin metabolites following intravenous bradykinin. During NHP-554C 162.5 mg/d, but not during ASA, bradykinin significantly increased urinary 2,3-dinor-6-keto-PGF1α. Nevertheless, 11-dehydro-thromboxane B2 and 2,3-dinor-6-keto-PGF1α responses to bradykinin were statistically similar during ASA and NHP-554C. In conclusion, at doses of 81 and 162.5 mg/d immediate- and extended-release aspirin selectively decrease basal thromboxane production. Both forms of aspirin decrease bradykinin-stimulated thromboxane and prostacyclin production, but some stimulated prostacyclin production remains during treatment with NHP-554C.

Gamboa|Jorge L|JL|
Devin|Jessica K|JK|
Ramirez|Claudia E|CE|
Yu|Chang|C|
Nian|Hui|H|
Lee|Rhonda H|RH|
Brown|Nancy J|NJ|

Aspirin thromboxane prostacyclin bradykinin


Low expression of NSD1, NSD2, and NSD3 define a subset of human papillomavirus-positive oral squamous carcinomas with unfavorable prognosis.

Abstract:
BACKGROUND
Frequent mutations in the nuclear receptor binding SET domain protein 1 (NSD1) gene have been observed in head and neck squamous cell carcinomas (HNSCC). NSD1 encodes a histone 3 lysine-36 methyltransferase. NSD1 mutations are correlated with improved clinical outcomes and increased sensitivity to platinum-based chemotherapy agents in human papillomavirus-negative (HPV-) tumors, despite weak T-cell infiltration. However, the role of NSD1 and related family members NSD2 and NSD3 in human papillomavirus-positive (HPV+) HNSCC is unclear.

METHODS
Using data from over 500 HNSCC patients from The Cancer Genome Atlas (TCGA), we compared the relative level of mRNA expression of NSD1, NSD2, and NSD3 in HPV+ and HPV- HNSCC. Correlation analyses were performed between T-cell infiltration and the relative level of expression of NSD1, NSD2, and NSD3 mRNA in HPV+ and HPV- HNSCC. In addition, overall survival outcomes were compared for both the HPV+ and HPV- subsets of patients based on stratification by NSD1, NSD2, and NSD3 expression levels.

RESULTS
Expression levels of NSD1, NSD2 or NSD3 were not correlated with altered lymphocyte infiltration in HPV+ HNSCC. More importantly, low expression of NSD1, NSD2, or NSD3 correlated with significantly reduced overall patient survival in HPV+, but not HPV- HNSCC.

CONCLUSION
These results starkly illustrate the contrast in molecular features between HPV+ and HPV- HNSCC tumors and suggest that NSD1, NSD2, and NSD3 expression levels should be further investigated as novel clinical metrics for improved prognostication and patient stratification in HPV+ HNSCC.

Head and neck squamous cell carcinoma
The Cancer Genome Atlas
Epigenetics
HPV
Head and neck cancer
Histone methyltransferase
WHSC1
WHSC1L1


Stress impairs the efficacy of immune stimulation by CpG-C: Potential neuroendocrine mediating mechanisms and significance to tumor metastasis and the perioperative period.

Abstract: We recently reported that immune stimulation can be compromised if animals are simultaneously subjected to stressful conditions. To test the generalizability of these findings, and to elucidate neuroendocrine mediating mechanisms, we herein employed CpG-C, a novel TLR-9 immune-stimulating agent. Animals were subjected to ongoing stress (20-h of wet cage exposure) during CpG-C treatment, and antagonists to glucocorticoids, β-adrenoceptor, COX2, or opioids were employed (RU486, nadolol, etodolac, naltrexone). In F344 rats, marginating-pulmonary NK cell numbers and cytotoxicity were studied, and the NK-sensitive MADB106 experimental metastasis model was used. In Balb/C mice, experimental hepatic metastases of the CT-26 colon tumor were studied; and in C57BL/6J mice, survival rates following excision of B16 melanoma was assessed - both mouse tumor models involved surgical stress. The findings indicated that simultaneous blockade of glucocorticoid and β-adrenergic receptors improved CpG-C efficacy against MADB106 metastasis. In mice bearing B16 melanoma, long-term survival rate was improved by CpG-C only when employed simultaneously with blockers of glucocorticoids, catecholamines, and prostaglandins. Prolonged stress impaired CpG-C efficacy in potentiating NK activity, and in resisting MADB106 metastasis in both sexes, as also supported by in vitro studies. This latter effect was not blocked by any of the antagonists or by adrenalectomy. In the CT26 model, prolonged stress only partially reduced the efficacy of CpG-C. Overall, our findings indicate that ongoing behavioral stress and surgery can jeopardize immune-stimulatory interventions and abolish their beneficial metastasis-reducing impacts. These findings have implications for the clinical setting, which often involve psychological and physiological stress responses during immune-stimulation.

Levi|B|B|
Matzner|P|P|
Goldfarb|Y|Y|
Sorski|L|L|
Shaashua|L|L|
Melamed|R|R|
Rosenne|E|E|
Page|G G|GG|
Ben-Eliyahu|S|S|

Immune stimulation
CpG-C
Ongoing stress
Glucocorticoids
NK
Catecholamines
Prostaglandins