Efficacy and safety of apatinib treatment for gastric cancer, hepatocellular carcinoma and non-small cell lung cancer: a meta-analysis.

Abstract: Apatinib (Aitan®, brand name in China) is a new anti-antiangiogenic agent that has recently been approved for the treatment of advanced gastric cancer (GC) in China. Nevertheless, its therapeutic efficacy against other types of advanced solid tumors remains unclear. This meta-analysis examines the short-term efficacy and safety of apatinib or combination therapy for GC, hepatocellular carcinoma (HCC) and non-small-cell lung cancer (NSCLC); and provides a discussion of its anti-angiogenesis therapy applications. Seven clinical studies met the inclusion criteria. The treatment of cancers using apatinib was more successful compared to therapy without apatinib. Both objective response rates (ORRs) and disease control rates (DCRs) were significantly improved in the apatinib group compared to those in the control group (RR=2.18, 95% CI 1.30-3.65; RR=2.09, 95% CI 1.21-3.60). The DCR of 850 mg qd and 750 mg qd were higher than those in the control group (P<0.05). Based on the short-term acute adverse reactions of apatinib, significant differences between groups were found for hypertension, urine protein, hand foot syndrome, and gastrointestinal reactions (diarrhea), while no significant differences were found for myelosuppression, nausea and vomiting. Moreover, the results showed that apatinib prolonged patient survival (HR=0.38, 95% CI: 0.28-0.52), and the effect was more pronounced in patients treated with 750 mg qd or 850 mg qd of apatinib than in those treated with a dose of ≤500 mg qd. Additionally, compared to its second-line application, the third-line application was shown to further reduce the risk ratio in patients. Furthermore, overall survival was longer in patients treated with apatinib. Apatinib was shown to have certain short-term effects and survival benefits on GC, HCC, and NSCLC with controllable adverse effects.

Xue|Jin-Min|JM| Astère|Manirakiza|M| Zhong|Mao-Xi|MX| Lin|Han|H| Shen|Jin|J| Zhu|Yu-Xi|YX|

apatinib
meta-analysis
angiogenesis
malignant tumor
vascular endothelial growth factor


Milk Protein-Derived Antioxidant Tetrapeptides as Potential Hypopigmenting Agents.

Abstract: Excessive accumulation of melanin can cause skin pigmentation disorders, which may be accompanied by significant psychological stress. Although many natural and synthetic products have been developed for the regulation of melanogenesis biochemistry, the management of unwanted skin pigmentation remains challenging. Herein, we investigated the potential hypopigmenting properties of peptide sequences that originated from milk proteins such as ĸ-casein and β-lactoglobulin. These proteins are known to inhibit melanogenesis and their hydrolysates are reported as antioxidant peptides. We synthesize tetrapeptide fragments of the milk protein hydrolysates and investigate the amino acids that are essential for designing peptides with tyrosinase inhibitory and antioxidant activities. We found that the peptide methionine-histidine-isoleucine-arginine amide sufficiently inhibits mushroom tyrosinase activity, shows potent antioxidant activity and effectively impedes melanogenesis in cultured melanocytes via cooperative biological activities. Our findings demonstrate the potential utility of the bioactive tetrapeptide from milk proteins as a chemical alternative to hypopigmenting agents.

Kong|Saerom|S| Choi|Hye-Ryung|HR| Kim|Yoon-Jeong|YJ| Lee|Yoon-Sik|YS| Park|Kyoung-Chan|KC| Kwak|Seon-Yeong|SY|

antioxidant
hypopigmenting
milk-protein derived tetrapeptides
tyrosinase inhibitor


Very low dose spironolactone protects experimentally-induced polycystic ovarian syndrome from insulin-resistant metabolic disturbances by suppressing elevated circulating testosterone.

Abstract: Polycystic ovarian syndrome (PCOS) is the most common endocrinological disorder in women of reproductive age and hyperandrogenism is a prominent feature of PCOS resulting in infertility and increased risk of developing metabolic disorders including insulin resistance (IR), abdominal adiposity, glucose intolerance and cardiovascular diseases. Spironolactone (SPL), a non-selective mineralocorticoid receptor (MR) antagonist, has been in wide clinical use for several decades. In this study, we investigated the effects of SPL on IR and metabolic disturbances in letrozole-induced PCOS rats. Eighteen adults female Wistar rats were randomly divided into 3 groups and treated with vehicle, letrozole (LET; 1 mg/kg) and LET + SPL (SPL; 0.25 mg/kg), p.o. once daily for 21 consecutive days. Results showed that LET treatment induced PCOS characterised by elevated plasma testosterone and luteinizing hormone (LH) accompanied with increased body weight and visceral adiposity, IR, glucose intolerance, dyslipidemia and altered histomorphological ovaries. Treatment with SPL however attenuated the elevated testosterone in LET-induced PCOS model accompanied with a reversal in all the observed alterations. Taken together, analysis of the physical, biochemical and histological evidences shows that the protective effect of this very low dose spironolactone may be through its anti-androgenic mechanism.

Adeyanju|Oluwaseun A|OA|
Falodun|Timothy O|TO|
Fabunmi|Oyesanmi A|OA|
Olatunji|Lawrence A|LA|
Soladoye|Ayodele O|AO|

Spironolactone
Testosterone
PCOS
Infertility
Insulin resistance


Second Hip Fracture: Incidence, Trends, and Predictors.

Abstract: Older persons who have suffered a hip fracture (HFx) are at increased risk of subsequent hip fractures. The cumulative incidence of a second hip fracture (SHFx) has been estimated in 8.4%; however, no studies have been carried out in our country, and the information on risk markers of SHFx is limited. The aim of this study was to estimate the incidence, explore trends, and examine predictors of SHFx in a suburban population of Spain. An observational longitudinal retrospective study was performed in a universal health coverage setting (Alcorcón, 1999-2011). Data were obtained from the area hospital discharge database. Annual incidence of HFx was estimated over 100,000 population (general and persons with HFx), and median time to SHFx by Kaplan-Meier tables. Cox regression was used for the analysis of association between SHFx and baseline predictors, measured by hazard ratio (HR). Among the 3430 patients who suffered a first HFx in the study period, 255 (7.4%) experienced a SHFx (4.5% of men and 8.5% of women). Median time between the first and second HFx was 3.7 years (SD 3.2). Annual incidence of HFx in population over 45 was 290.5 per 100,000 inhabitants (131.03 in men and 433.11 in women). Annual incidence of SHFx among persons with a HFx was 956.7 per 100,000 (1052.1 in women and 595.5 in men). There was a decline trend along the study period with an annual reduction of 10.4% (95% CI 7.7-13.0%; p < 0.001) in both sexes. The following associations were found: female sex (HR 1.41, 95% CI 0.97-2.02), age (HR 1.03, 95% CI 1.01-1.04), living in a nursing house (HR 1.46, 95% CI 1.10-1.94), and moderate to severe liver disease (HR 4.96, 95% CI 1.23-20.06). In our environment the occurrence of a SHFx is 7.4%, three-fold risk compared to no previous HFx. Being woman, elderly, living in a nursing home, and having severe to moderate liver disease may be important predictors of a SHFx. There seems to be adequate time between the first and the SHFx for interventions that may reduce the risk.

Second Hip Fracture
Incidence
Epidemiology
Osteoporosis


Nanostructuring Single-Molecule Polymeric Nanoparticles via Macromolecular Architecture.

Abstract: Heterogeneous polymer-based nanoparticles comprise a very promising family of materials for a broad range of applications. Here, we present a detailed study of structural heterogeneities in nanostructured single-molecule nanoparticles in various environments by means of atomistic molecular dynamics simulations. The nanoparticles consist of mikto-arm star copolymers with two types of chemically incompatible arms, namely poly(ethylene oxide) (PEO) and polystyrene (PS), (PS) n,(PEO) n, where n is the number of arms. The immiscibility between the two components gives rise to intramolecularly nanostructured particles. The nanostructured objects resemble either "Janus-like" or "patchy-like" particles, depending on the number or the length of the arms (or both) as well as the interaction with the surrounding medium. The degree of intramolecular heterogeneity increases with increasing number of arms and with decreasing affinity of star components to the polymer host. We provide a detailed analysis of the internal structure of the star-shaped particles, focusing on the intramolecular packing and the spatial arrangement of the arms. The results of our study can be used to design heterogeneous, internally nanostructured particles with two phases of distinct static properties for challenging specific applications of next-generation materials.

polymeric nanoparticles
atomistic simulations
intramolecular nanosegregation
mikto-arm copolymer stars
particle design


HuR enhances FSTL1 transcript stability to promote invasion and metastasis of squamous cell carcinoma.

Abstract: Squamous cell carcinoma (SCC) is a lethal malignancy with a high propensity for metastasis. Follistatin-like 1 (FSTL1), a pro-metastatic glycoprotein, is absent from healthy epithelia and aberrantly upregulated in SCC. The FSTL1 transcript encodes two alternative gene products whose dominance is post-transcriptionally regulated via a bistable switch. In healthy epithelia, FSTL1 mRNA is destabilized by binding of KH-type splicing regulatory protein (KSRP), and processed as a primary microRNA encoding miR-198. In SCC, KSRP downregulation terminates miR-198 processing, enabling FSTL1 translation. Here, we identify HuR (Human Antigen R) as an upstream regulator of FSTL1 and describe how downregulation of KSRP is permissive, but not sufficient, to promote sustained FSTL1 expression. Moreover, we demonstrate how the interplay between two RNA-binding proteins controls the translation of pro-oncogenic FSTL1. Increased expression of HuR in SCC outcompetes KSRP and enhances FSTL1 transcript stability, enabling persistent FSTL1 expression and activation of downstream metastatic pathways.

Sundaram|Gopinath M|GM|
Quah|Shan|S|
Guang|Lum Guo|LG|
Sampath|Prabha|P|

metastasis
squamous cell carcinoma
MicroRNA
RNA-binding proteins
cancer
cell proliferation


Psychometric properties of the brief version of the questionnaire of olfactory disorders in patients with chronic rhinosinusitis.

Abstract:
BACKGROUND
The Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS) is a 17-item instrument measuring olfactory-specific quality of life (QOL). However, in clinical research patients can be overwhelmed with multiple questionnaires. We recently developed the 7-item brief QOD-NS (B-QOD). Our objective was to evaluate the psychometric properties of the B-QOD in both the development (D) sample, and in a separate replication (R) sample.

METHODS
Testing on D (n = 203) and R (n = 281) samples included initial exploratory factor analysis (EFA), followed by internal reliability, information loss, and confirmatory factor analysis (CFA). Finally, incremental predictive utility analysis (IPUA) was performed by correlating the B-QOD with the 22-item Sino-Nasal Outcome Test (SNOT-22) survey.

RESULTS
EFAs of both D and R demonstrated an underlying single-factor structure (eigenvalue = 4.17 and 3.57, respectively) with comparable loading factors (R > 0.30 for both). B-QOD also had good internal reliability in both D and R (Cronbach's alpha = 0.88 and 0.83, respectively). Also, there is minimal information loss with B-QOD compared to QOD-NS in both D and R (R = 0.98 and 0.96, respectively). CFA indicates that the B-QOD single-factor model has good overall fit as measured by the Comparative Fit Index (CFI) and the Standardized Root Mean Squared Residuals (SRMSR) in the D and R samples (CFI = 0.99 and 0.97; SRMSR = 0.035 and 0.053). IPUA shows that the QOD-NS offers no additional predictive benefit of SNOT-22 scores when compared with B-QOD.

CONCLUSION
The 7-item B-QOD captures a structurally coherent and reliable single dimension, with minimal information loss and excellent external predictive utility when compared to the QOD-NS.

Mattos|Jose L|JL|0000-0001-8766-1626
Bodner|Todd E|TE|
Mace|Jess C|JC|
Schlosser|Rodney J|RJ|
Beswick|Daniel M|DM|0000-0001-8612-5442
Ramakrishnan|Vijay R|VR|
Alt|Jeremiah A|JA|
Payne|Spencer C|SC|0000-0001-9736-4561
Smith|Timothy L|TL|0000-0002-6424-7083
Soler|Zachary M|ZM|

quality of life
olfaction disorders
patient reported outcome measures
sinusitis
smell


Clinically applicable cases of anti-programmed cell death protein 1 immunotherapy for colorectal cancer patients.

Abstract: We investigated the prevalence and characteristics of defective mismatch repair (dMMR) in colorectal cancer (CRC) patients who would potentially benefit from anti-programmed cell death protein 1 (PD-1) immunotherapy. Medical records were obtained and reviewed for 1147 patients who underwent surgical resection of stage I-IV CRC, in whom universal screening for Lynch syndrome using immunohistochemistry for MMR proteins had been undertaken. The molecular characteristics of dMMR CRCs were also investigated. Defective MMR accounted for 5.2% of stage I-IV CRC patients, including 12 (1.0% of all CRC patients) who had stage IV disease or recurrence after curative resection (n = 6 each). These 12 patients included patients with LS (n = 3) and Lynch-like syndrome (n = 1). Defective MMR tumors were predominantly located in the right-sided colon (P < 0.01). Approximately 1% of stage I-IV CRC patients could potentially benefit from anti-PD-1 immunotherapy, while one-third would require genetic counseling and/or MMR gene testing.

Chikatani|Kenichi|K| Chika|Noriyasu|N| Suzuki|Okihide|O| Sakimoto|Takehiko|T| Ishibashi|Keiichiro|K| Eguchi|Hidetaka|H| Okazaki|Yasushi|Y| Ishida|Hideyuki|H|

D013505:Digestive System Surgical Procedures

D061026:Programmed Cell Death 1 Receptor

Colorectal cancer
Defective mismatch repair
Anti-PD-1 blockade


SARS-Cov-2 and environmental protection: A collective psychology agenda for environmental psychology research.

Abstract: While the virus SARS-CoV-2 spreads all over the world, most countries have taken severe measures to protect their citizens and slow down the further spread of the disease COVID-19. These measures affect individuals, communities, cities, countries, and the entire planet. In this paper, we propose that the tremendous consequences of the corona crisis invite environmental psychology to focus more strongly on research questions that address major societal challenges from a collective psychology perspective. In particular, we stress that the corona crisis may affect how people appraise - and potentially respond to - the looming climate crisis. By consistently pointing out systemic links and their human factor, environmental psychology can become central to a scientific agenda of a sustainable 'post-corona society'. In order to provide a framework for future research towards a sustainable societal transformation, we build on the Social Identity Model of Pro-Environmental Action (SIMPEA) and extend its scope to understand people's responses following the corona crisis. The model allows predictions of previously not explicitly included concepts of place attachment, nature connectedness, basic psychological needs, and systems thinking. It may serve as a guiding framework for a better understanding of the transformation towards a sustainable future.

Reese|Gerhard|G|
Hamann|Karen R S|KRS|
Heidbreder|Lea M|LM|
Loy|Laura S|LS|
Menzel|Claudia|C|
Neubert|Sebastian|S|
Tröger|Josephine|J|
Wullenkord|Marlis C|MC|

Collective psychology
Corona crisis
Transformation
Social identity
Place attachment
Systems thinking


Non-Invasive Tissue Oximetry-An Integral Puzzle Piece.

Abstract: Non-invasive tissue oximetry is a monitoring method for continuous assessment of tissue oxygenation, which may aid in detection of hemodynamic instability and otherwise unnoticed hypoxia. Numerous studies focused on using non-invasive tissue oximetry intraoperatively, proposing its predictive value in relation to clinical outcome. Tissue oximetry may be part of standard monitoring practice for brain monitoring during cardiac surgery in many clinical centers; however, the monitoring method can be deployed in numerous clinical settings. This succinct overview aims to determine the role of non-invasive tissue oximetry in current clinical practice.

Vranken|Nousjka P A|NPA|
Weerwind|Patrick W|PW|

tissue oximetry
cardiopulmonary bypass
near-infrared spectroscopy
patient monitoring


Management of chyle leakage after thyroidectomy, cervical lymph node dissection, in patients with thyroid cancer.

Abstract:
BACKGROUND
The purpose of this study was to evaluate the incidence and pattern of chyle leakage after thyroidectomy and/or cervical lymph node dissection and to establish management protocols for chyle leakage.

METHODS
Patients who underwent surgical management for thyroid cancer were analyzed retrospectively.

RESULTS
For this study, 131 patients with chyle leakage were identified; the overall incidence was 0.9%. Of them, 43.7% of patients underwent central neck dissection without lateral neck dissection, and chyle leakage was easily controlled with conservative management. Patients whose chyle drainage was reduced by >50% after dietary modification had a significantly shorter hospital stay (P < .001); NPO was the most effective dietary modification.

CONCLUSION
The occurrence of chyle leakage after central compartment dissection even without lateral neck dissection was not rare, but was easily controlled with conservative management. Surgical management should be considered if the drainage amount does not decrease by >50% of the original amount of the day of detection after 2 days of NPO.

chyle leakage
conservative management
dietary modification
thoracic duct ligation


Photodynamic Action of Single-Walled Carbon Nanotubes.

Abstract: Photodynamic therapy is achieved by the combination of photosensitizers, harmless visible or near-infrared (NIR) light, and molecular oxygen (O2). Photosensitizers transfer their absorbed light energy to O2 to generate a major active species in photodynamic therapy, singlet oxygen. In this review, I will discuss the possibility of single-walled carbon nanotubes as NIR photosensitizers, while explaining the general photophysics and photochemistry underlying photodynamic therapy as well as summarizing recent advances in the purification technologies for single-walled carbon nanotubes to reduce their toxicity concerns.

D037742:Nanotubes, Carbon
D010778:Photochemotherapy
D026082:Singlet Oxygen

photosensitizer
singlet oxygen
chirality sorting
near-IR light
reactive oxygen species
surface chemistry


Saliva-based PCR tests for SARS-CoV-2 detection.

Abstract: The outbreak of novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. Nasopharyngeal swabs are widely used in polymerase chain reaction (PCR) test to detect SARS-CoV-2. However, the collection of nasopharyngeal swabs has a series of drawbacks concerning exposure of healthcare staff, difficulty in collection, and discomfort of patients. Therefore, an alternative noninvasive sample for diagnostic of emerging viral diseases is required. The usefulness of saliva screening tests is compared to conventional swab tests in this report. The results suggest that saliva could be a reliable sample for detecting SARS-CoV-2.

Takeuchi|Yoshimasa|Y| Furuchi|Mika|M| Kamimoto|Atsushi|A| Honda|Kazuya|K| Matsumura|Hideo|H| Kobayashi|Ryutaro|R|


Understanding ALS: new therapeutic approaches.

Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease associated with motor neuron degeneration, muscle atrophy and paralysis. Although numerous pathological mechanisms have been elucidated, ALS remains an invariably fatal disease in the absence of any effective therapy. The heterogeneity of the disease and the failure to develop satisfactory therapeutic protocols reinforce the view that ALS is a multi-factorial and multi-systemic disease. Thus, a better understanding of the pathogenic mechanisms and study of the potential pathological relationship between the various cellular processes is required to ensure efficacious therapy. The pathogenic mechanisms associated with ALS are reviewed, and the strengths and limitations of some new therapeutic approaches are discussed.

D000690:Amyotrophic Lateral Sclerosis
D000818:Animals
D000911:Antibodies, Monoclonal
D005081:Exercise Therapy
D015316:Genetic Therapy
D006801:Humans

therapeutic approaches
amyotrophic lateral sclerosis
ALS-associated genes
complexity of ALS pathogenesis
growth factors
mutant SOD1 toxicity
neuromuscular disease
oxidative stress
skeletal muscle
stem cells


Evaluation for the Genetic Association between Store-Operated Calcium Influx Pathway (STIM1 and ORAI1) and Human Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Infection.

Abstract: Hepatocellular carcinoma (HCC) often develops from chronic hepatitis B (CHB) through replication of hepatitis B virus (HBV) infection. Calcium (Ca2+) signaling plays an essential role in HBV replication. Store-operated calcium (SOC) channels are a major pathway of Ca2+ entry into non-excitable cells such as immune cells and cancer cells. The basic components of SOC signaling include the STIM1 and ORAI1 genes. However, the roles of STIM1 and ORAI1 in HBV-mediated HCC are still unclear. Thus, long-term follow-up of HBV cohort was carried out in this study. This study recruited 3631 patients with chronic hepatitis (345 patients with HCC, 3286 patients without HCC) in a Taiwanese population. Genetic variants of the STIM1 and ORAI1 genes were detected using an Axiom CHB1 genome-wide array. Clinical associations of 40 polymorphisms were analyzed. Three of the STIM1 single-nucleotide polymorphisms (SNPs) (rs6578418, rs7116520, and rs11030472) and one SNP of ORAI1 (rs6486795) showed a trend of being associated with HCC disease (p < 0.05). However, after correction for multiple testing, none of the SNPs reached a significant level (q > 0.05); in contrast, neither STIM1 nor ORAI1 showed a significant association with HCC progression in CHB patients. Functional studies by both total internal reflection fluorescence images and transwell migration assay indicated the critical roles of SOC-mediated signaling in HCC migration. In conclusion, we reported a weak correlation between STIM1/ORAI1 polymorphisms and the risk of HCC progression in CHB patients.

Muhammad Irham|Lalu|L|
Chou|Wan-Hsuan|WH|
Wang|Yu-Shiuan|YS|
Adikusuma|Wirawan|W|0000-0001-9165-690X
Sung-Ching Wong|Henry|H|
Aryani Perwitasari|Dyah|D|
Huang|Wan-Chen|WC|
Chen|Ben-Kuen|BK|
Yang|Hwai-I|HI|0000-0002-3433-942X
Chang|Wei-Chiao|WC|

STIM1
ORAI1
hepatocellular carcinoma (HCC)
chronic hepatitis B (CHB)
hepatitis B virus (HBV)
single-nucleotide polymorphism (SNP)


Macrobrachium rosenbergii nodavirus (MrNV)-CP-RNA-2 DNA vaccine confers protective immunity in giant freshwater prawn Macrobrachium rosenbergii against MrNV infection.

Abstract: Macrobrachium rosenbergii Nodavirus (MrNV) causes white tail disease (WTD) in Giant freshwater prawn Macrobrachium rosenbergii which leads to immense economic losses in hatcheries and farms. In the present study, we cloned the capsid protein gene of MrNV-CP-RNA-2 (1146 bp) into a DNA vaccine vector pVAX1 to form MrNV-CP-RNA-2- pVAX1. The bacterial transformant, containing the MrNV-CP gene, was coated on the fish diet pellets and fed to juvenile M. rosenbergii for 40 days. After the vaccine delivery, group of M. rosenbergii were challenged with virulent MrNV on 20 and 40th days post-vaccination (dpv) respectively and monitored for the survival. The non-vaccinated M. rosenbergii succumbed to death (100%) within 5 days, whereas the MrNV-CP-RNA-2- pVAX1 treated groups had the survivals of 60 and 80% in 20 and 40 dpv respectively (P ≤ 0.001). To study the MrNV infection level, double step PCR was performed at different dpv. The results revealed that in 20 dpv group, the infection was decreased to 65% and in 40 dpv group the infection decreased to 69% from control diet fed prawns (P < 0.001). Haematological parameters like coagulation time, total haemocyte count (THC) and oxyhaemocyanin levels were performed for the control and vaccinated prawns. The vaccination helped to decrease the time of coagulation, improved THC and oxyhaemocyanin levels at a significant level (p < 0.001) when compared to the non-vaccinated group. The immunological parameters like prophenol oxidase (ProPO), superoxide anion and intra-agar lysozyme activity were also performed and the results revealed that the level of proPO, superoxide anion and lysozyme activities were significantly (P ≤ 0.05) increased in 20 and 40 dpv groups respectively, when compared with the non-vaccinated groups. Based on the vaccination trials, the DNA vaccine construct MrNV-CP-RNA-2-pVAX1 effectively improved the survival against MrNV challenge, helped to decrease viral load and enhanced the immune system to protect the prawn from MrNV infection. This vaccine construct is highly useful to protect the M. rosenbergii from MrNV infection.

Citarasu|Thavasimuthu|T|
Lelin|Chinnadurai|C|
Thirumalaikumar|Eswaramoorthy|E|
Michael Babu|Mariavincent|M|
Vakharia|Vikram N|VN|


Light-Intensity Physical Activity in a Large Prospective Cohort of Older US Adults: A 21-Year Follow-Up of Mortality.

Abstract:
BACKGROUND
Studies show that regular moderate to vigorous physical activity is associated with a lower risk of cardiovascular disease, certain cancers, and premature death, but few studies have examined associations of light-intensity physical activity (LPA) and mortality, especially among older adults.

OBJECTIVES
The aim of this study was to investigate the association of LPA with the risks of death from all causes, cancer, cardiovascular diseases, and respiratory diseases among older adults in the Cancer Prevention Study-II Nutrition Cohort (CPS-II NC).

METHODS
Analyses included 123,232 participants in CPS-II NC, among whom 46,829 died during follow-up (1993-2014). Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for self-reported leisure time LPA associated with mortality.

RESULTS
Engaging in little or no LPA (<3 metabolic equivalent [MET]-h/week) was associated with a 16% higher risk of all-cause mortality (HR 1.16, 95% CI 1.12-1.20) compared to engaging in some LPA (3 to <9 MET-h/week) after adjusting for moderate to vigorous physical activity. However, there was no evidence of a dose-response relationship. A statistically significant interaction with age suggested that more LPA was associated with a lower risk of respiratory disease mortality only among participants aged ≥70 years (21+ vs. 3 to <9 MET-h/week, HR 0.78, 95% CI 0.66-0.91; pint = 0.003).

CONCLUSIONS
In this prospective study of older adults, accumulating little/no leisure time LPA was associated with a higher risk of mortality. It is of substantial public health value to demonstrate the potential benefits of engaging in any activity, even if light in intensity, among older adults given the aging US population.

Rees-Punia|Erika|E|
Deubler|Emily|E|
Campbell|Peter|P|
Gapstur|Susan M|SM|
Patel|Alpa|A|

Light-intensity physical activity
Aging
Cancer prevention study
Leisure time physical activity


Sugar-feeding behaviour and longevity of European Culicoides biting midges.

Abstract: Most haematophagous insect vectors can also use sugar as an energy source; thus their sugar-feeding behaviour influences their longevity and blood-feeding rate and hence their vectorial capacity. Scant information is available on the sugar-feeding behaviour of Culicoides Latreille biting midges (Diptera: Ceratopogonidae), which are vectors of bluetongue and Schmallenberg viruses. The longevity of laboratory-reared Culicoides nubeculosus (Meigen) under fluctuating temperatures (16 and 28 °C) and with access to water or water and blood was on average 6.4 days and 8.9 days, respectively, which was around one third of the lifespan of siblings with access to sugar or sugar and blood (22.2 days and 27.1 days, respectively). Access to honeydew significantly increased the midge's longevity, whereas the provision of extrafloral nectaries had no impact. Females with access to sugar produced a significantly higher number of eggs (65.5 ± 5.2) than their starved sisters (45.4 ± 8.4). More than 80% of field-caught female Culicoides from the two most abundant European groups, Obsoletus (n = 2243) and Pulicaris (n = 805), were fructose-positive. Fructose-positivity was high in all physiological stages and no seasonal variability was noted. The high rate of natural sugar feeding of Culicoides offers opportunities for the development of novel control strategies using toxic sugar baits and for the monitoring of vector-borne diseases using sugar-treated FTA (nucleic acid preservation) cards in the field.

vectors
blood
honeydew
control strategies
Aphids
fructose
nectar


Needs of parents and professionals to improve shared decision-making in interprofessional maternity care practice: A qualitative study.

Abstract:
BACKGROUND
Shared decision-making (SDM) is a critical but challenging component of high quality maternity care. In co-creation with parents and professionals, we are developing an intervention to improve SDM. As a first step we aimed to explore the experiences and needs of parents and professionals regarding shared decision-making in interprofessional antenatal, natal, and postnatal care.

METHODS
We organized 11 focus groups in the Netherlands in November and December 2016. Parents, primary care midwives, hospital-based midwives, obstetricians, obstetric nurses, and maternity care assistants participated.

RESULTS
Parents and professionals recognized the SDM steps of introducing a decision (choice talk) and discussing options (option talk), but most parents did not seem to discuss preferences and weigh options with professionals before making their final decision (decision talk). Barriers to SDM were often related to interprofessional collaboration, while good communication skills of parents and professionals facilitated SDM. An intervention to improve SDM would need to: (a) increase awareness and offer insight into the SDM process and roles and responsibilities of parents and professionals, (b) develop good communication skills, and (c) encourage interprofessional collaboration. The preferred design of the intervention was online, interactive, and practical.

CONCLUSIONS
Parents and professionals will benefit from an intervention designed to improve SDM. A practical e-learning for all maternity care providers and e-health information for parents seems most appropriate. Key elements for the e-learning are raising awareness of the roles and responsibilities of parents and professionals, developing good communication skills and encouraging interprofessional collaboration. This requires a variety of educational strategies.

Molenaar|Joyce|J|0000-0002-8025-040X
Korstjens|Irene|I|
Hendrix|Marijke|M|
de Vries|Raymond|R|
Nieuwenhuijze|Marianne|M|

parents
shared decision-making
maternity care
interprofessional collaboration
needs assessment


Individuality meets plasticity: Endocrine phenotypes across male dominance rank acquisition in guinea pigs living in a complex social environment.

Abstract: The time of dominance rank acquisition is a crucial phase in male life history that often affects reproductive success and hence fitness. Hormones such as testosterone and glucocorticoids can influence as well as be affected by this process. At the same time, hormone concentrations can show large individual variation. The extent to which such variation is repeatable, particularly in dynamic social settings, is a question of current interest. The aim of the present study was therefore to investigate how dominance rank and individual differences contribute to variance in hormone concentrations during male rank acquisition in a complex social environment. For this purpose, dominance rank as well as baseline testosterone, baseline cortisol, and cortisol responsiveness after exposure to a novel environment were determined in colony-housed guinea pig males from late adolescence through adulthood. Hormone-dominance relationships and repeatability of hormone measures beyond their relation to rank were assessed. There was a significant positive relationship between baseline testosterone and rank, but this link became weaker with increasing age. Baseline cortisol or cortisol responsiveness, in contrast, were not significantly related to dominance. Notably, all three endocrine parameters were significantly repeatable independent of dominance rank from late adolescence through adulthood. Baseline testosterone and cortisol responsiveness showed a significantly higher repeatability than baseline cortisol. This suggests that testosterone titres and cortisol responsiveness represent stable individual attributes even under complex social conditions.

Mutwill|Alexandra M|AM|
Schielzeth|Holger|H|
Zimmermann|Tobias D|TD|
Richter|S Helene|SH|
Kaiser|Sylvia|S|
Sachser|Norbert|N|

Plasticity
Guinea pigs
Glucocorticoids
Repeatability
Baseline testosterone
Baseline cortisol
Cortisol responsiveness
Adolescence
Social complexity
Variance partitioning


A comparison of contraceptive services for adolescents at school-based versus community health centers in Oregon.

Abstract:
OBJECTIVE
To compare Oregon school-based health centers (SBHCs) with community health centers (CHCs) as sources of adolescent contraceptive services.

DATA SOURCES
Oregon electronic health record data, 2012-2016.

STUDY DESIGN
We compared clinic-level counseling rates and long-acting reversible contraception (LARC) provision, adolescent populations served, and visit-level LARC provision time trends. We evaluated adjusted associations between LARC provision and Title X participation by clinic type.

DATA COLLECTION/EXTRACTION METHODS
We used diagnosis and procedure codes to identify contraceptive counseling and provision visits, excluding visits for adolescents not at risk of pregnancy.

PRINCIPAL FINDINGS
CHCs were more likely to provide LARC on-site than SBHCs (67.2% vs. 36.4%, respectively). LARC provision increased more at SBHCs (5.8-fold) than CHCs (2-fold) over time. SBHCs provided more counseling visits per clinic (255 vs. 142) and served more young and non-White adolescents than CHCs. The adjusted probability of LARC provision at Title X SBHCs was higher than non-Title X SBHCs (4.4% [3.9-4.9] vs. 1.7% [1.4-2.0]), but there was no significant association at CHCs.

CONCLUSIONS
In Oregon, CHCs and SBHCs are both important sources of adolescent contraceptive services, and Title X plays a crucial role in SBHCs. Compared with CHCs, SBHCs provided more counseling, showed a larger increase in LARC provision over time, and served more younger and non-White adolescents.

contraception
adolescent
community health center
school-based health center
SBHC
CHC
LARC


Performance study of compounded biocover material for methane removal based on cattle manure compost.

Abstract: Methane is the second most significant greenhouse gas. Landfill cover soils play an important role in mitigation of methane emission from critical sources - Landfills. In this study, methane removal biocover materials based on cattle manure compost (CMC) were constructed and its performance was investigated. When comparing CH4 removal abilities of sand (S), clay soil (CS), paddy soil (PS) and CMC, CMC was the most effective biocover material for the reduction of methane emission. The maximum removal rate (Vmax) and half saturation constant (Km) of CMC peaked at 3451.25 ± 18.57 μg g(-1) h(-1) and 3.67 ± 0.02 × 10(5) ppm, respectively, which are higher than those in previous studies. Thereafter, three compounded biocover materials (CBMs) were established based on the mixture of CMC and other three materials (ratio of 2:8). The rate of the three CBMs was enhanced by 13.56, 13.27 and 16.42 times, respectively, more than the S, CS and PS by adding CMC. Saturated water content of 80% and 35 °C were found to be the optimum moisture and temperature, respectively, for CBMs. Analysis of community diversity using terminal restriction fragment length polymorphism (T-RFLP) showed that the diversity and evenness indexes of the CBMs decreased after adding CMC; Type I methanotroph was the most dominated methanotroph in the CBMs. CMC not only influenced bacterial community but also improved nutrient and CH4 removal capacity of CBMs. All results showed that CMC and CBMs could effectively remove CH4, and the screening and construction of CBMs are important for decreasing CH4 emission.

Wei|Wenping|W| Deng|Hui|H| Li|Guoxue|G| Wang|Xue|X| Lu|Jianjiang|J|

compounded biocover material
cattle manure compost
T-RFLP
methanotroph
Methane mitigation emission


Symptom prevalence, bother, and treatment satisfaction in men with lower urinary tract symptoms in Southeast Asia: a multinational, cross-sectional survey.

Abstract:
PURPOSE
The overall objective of the survey was to systematically examine patients' perspectives on lower urinary tract symptoms (LUTS) and their treatment in Southeast Asia.

METHODS
A multinational cross-sectional survey involving adult men seeking consultation at urology outpatient clinics because of LUTS in Southeast Asia was conducted using convenience sampling. Self-reported prevalence, bother, treatment and treatment satisfaction of selected LUTS including urgency, nocturia, slow stream, and post-micturition dribble were evaluated.

RESULTS
In total, 1535 eligible patients were enrolled in the survey. A majority of respondents were aged 56-75 years, not employed, and had not undergone prostate operation before. Overall, the self-reported prevalence of nocturia was 88% (95% CI 86-90%), slow stream 61% (95% CI 59-63%), post micturition dribble 55% (95% CI 52-58%), and urgency 52% (95% CI 49-55%). There were marked differences in the country specific prevalence of LUTS complaints. Frequently, symptoms coexisted and were combined with nocturia. More than half of patients felt at least some degree of bother from their symptoms: 61% for urgency, 57% for nocturia, 58% for slow stream, and 60% for post-micturition dribble. Before seeing the present urologists, nearly half of patients have received some form of prescribed treatment and more than 80% of patients indicated they would like to receive treatment.

CONCLUSION
Men who sought urologist care for LUTS often presented with multiple symptoms. Nocturia emerged as the most common symptom amongst the four core symptoms studied.

Prevalence
Lower urinary tract symptoms
Adult
Cross-sectional studies
Epidemiology surveys and questionnaires
Male


Abstract:
The 10-year results after national introduction of pelvic lymph node staging in Danish intermediate-risk endometrial cancer patients not given postoperative radiotherapy. Gitte Ørtoft; Claus Høgdall; Estrid S Hansen; Margit Dueholm.

OBJECTIVE
To prepare for the national introduction of sentinel node staging, we evaluated the consequences of the previous national decision to introduce lymph node staging in intermediate-risk endometrial cancer patients (grade 1/2 with > 50% or grade 3 with < 50% myometrial invasion) by determining the number of patients upstaged by lymphadenectomy and whether upstaging affected the survival and recurrence patterns of non-staged patients and patients with and without lymph node metastases.

STUDY DESIGN
In a national cohort study, 2005-12, 1294 stage I-IV patients who should have been offered lymphadenectomy were progressively registered. The number of patients upstaged by lymphadenectomy, 10-year survivals were evaluated by Kaplan-Meier analysis and adjusted Cox regression.

RESULTS
This study demonstrates that it takes time to introduce lymphadenectomy at a national level, as indicated by the increasing number of cases staged per year, from 12% in 2005 to 74% in 2012. Pelvic lymphadenectomy was performed in 43.8% (567/1294) and lymph node metastases were found in 13.6% (77/567). As 54 patients had further dissemination outside the uterine body, only 23 patients (6%) were upstaged from stage I to IIIC. Compared to lymph node-negative patients, the 77 patients with lymph node metastasis had significantly lower overall, (55% versus 68%), disease-specific (64% versus 86%), and progression-free survival (51% versus 77%), mainly due to non-local recurrences including a high number of paraaortic recurrences. In 873 final stage I intermediate-risk patients, 10-year survival and recurrence rates were not significantly lower in non-staged as compared to lymph node-negative patients (overall survival 62% versus 70%: disease-specific survival: 90% versus 90%, progression-free survival: 81% vs 83%), probably due to the low number of patients upstaged from stage I to stage IIIC.

CONCLUSION
Lymph node metastases were present in 13.6% of patients with intermediate-risk who underwent pelvic lympadenectomy, and these patients had a lower 10-year survival than lymph node-negative patients. Because lymphadenectomy upstaged only 6% from stage I to stage IIIC, survival and recurrence rates were not significantly compromised in non-staged as compared to lymph node-negative intermediate-risk stage I patients. Sentinel node staging has now been implemented in Danish intermediate-risk endometrial cancer patients.

Ørtoft|Gitte|G|
Høgdall|Claus|C|
Hansen|Estrid S|ES|
Dueholm|Margit|M|

D015331:Cohort Studies
D003718:Denmark
D016889:Endometrial Neoplasms
D005260:Female
D006801:Humans
D008197:Lymph Node Excision
D008198:Lymph Nodes
D009364:Neoplasm Recurrence, Local
D009367:Neoplasm Staging

Intermediate-risk
Endometrial cancer
Radiotherapy
Lymphadenectomy
Survivals
Recurrence


Evolution of plasticity in the city: urban acorn ants can better tolerate more rapid increases in environmental temperature.

Abstract: Because cities contain high levels of impervious surfaces and diminished buffering effects of vegetation cover, urbanized environments can warm faster over the day and exhibit more rapid warming over space due to greater thermal heterogeneity in these environments. Whether organismal physiologies can adapt to these more rapid spatio-temporal changes in temperature rise within cities is unknown, and exploring these responses can inform not only how plastic and evolutionary mechanisms shape organismal physiologies, but also the potential for organisms to cope with urban development. Here, we examined how plasticity in thermal tolerance under faster and slower rates of temperature change might evolve in response to the more rapid spatio-temporal temperature rise in cities. We focused on acorn ants, a temperature-sensitive, ground-dwelling ant species that makes its home inside hollowed out acorns. We reared acorn ant colonies from urban and rural populations under a common garden design in the laboratory and assessed the thermal tolerances of F1 offspring workers using both fast (1°C min-1) and slow (0.2°C min-1) rates of temperature change. Relative to the rural population, the urban population exhibited higher heat tolerance when the temperature was increased quickly, providing evidence that temperature ramp-rate plasticity evolved in the urban population. This result was correlated with both faster rates of diurnal warming in urban acorn ant nest sites and greater spatial heterogeneity in environmental temperature across urban foraging areas. By contrast, rates of diurnal cooling in acorn ant nest sites were similar across urban and rural habitats, and correspondingly, we found that urban and rural populations responded similarly to variation in the rate of temperature decrease when we assessed cold tolerance. Our study highlights the importance of considering not only evolutionary differentiation in trait means across urbanization gradients, but also how trait plasticity might or might not evolve.

Diamond|Sarah E|SE|
Chick|Lacy D|LD|
Perez|Abe|A|
Strickler|Stephanie A|SA|
Zhao|Crystal|C|

evolution
physiology
Thermal tolerance
microclimate
phenotypic plasticity
urban heat island


Connexins-Therapeutic Targets in Cancers.

Abstract: Connexins (Cx) are members of a protein family that forms intercellular channels localised in gap junction (GJ) plaques and single transmembrane channels called hemichannels. They participate in intercellular communication or communication between the intracellular and extracellular environments. Connexins affect cell homeostasis, growth and differentiation by enabling the exchange of metabolites or by interfering with various signalling pathways. Alterations in the functionality and the expression of connexins have been linked to the occurrence of many diseases. Connexins have been already linked to cancers, cardiac and brain disorders, chronic lung and kidney conditions and wound healing processes. Connexins have been shown either to suppress cancer tumour growth or to increase tumorigenicity by promoting cancer cell growth, migration and invasiveness. A better understanding of the complexity of cancer biology related to connexins and intercellular communication could result in the design of novel therapeutic strategies. The modulation of connexin expression may be an effective therapeutic approach in some types of cancers. Therefore, one important challenge is the search for mechanisms and new drugs, selectively modulating the expression of various connexin isoforms. We performed a systematic literature search up to February 2020 in the electronic databases PubMed and EMBASE. Our search terms were as follows: connexins, hemichannels, cancer and cancer treatment. This review aims to provide information about the role of connexins and gap junctions in cancer, as well as to discuss possible therapeutic options that are currently being studied.

cancer
connexin
gap junction
hemichannel
intercellular communication
cancer treatment


Cloning of Two Acetylcholinesterase Genes and Analysis of Point Mutations Putatively Associated with Triazophos Resistance in Chilo auricilius (Lepidoptera: Pyralidae).

Abstract: Acetylcholinesterase (AChE) is the target of organophosphate (OP) and carbamate insecticides. Mutations in the AChE gene (ace) leading to decreased insecticide susceptibility is the main resistance mechanism in insects. In this study, two Chilo auricilius acetylcholinesterase genes, designated as Caace1 and Caace2, were cloned using RT-PCR and RACE. Caace1 cDNA is 2534 bp, with ORF of 2082 bp, and it encodes an acetylcholinesterase 1 (CaAChE1) protein comprising a calculated 693 amino acid (aa) residues. Caace2 cDNA contains 2280 bp, with a full-length ORF of 1917 bp, encoding acetylcholinesterase 2 (CaAChE2) comprising a calculated 638 aa residues. At the aa level, CaAChE1 displays the highest similarity (97%) with the Chilo suppressalis AChE1, and CaAChE2 shows the highest similarity with the C. suppressalis AChE2 (99%). From the restriction fragment length polymorphism (RFLP) PCR (RFLP-PCR) analysis, one mutation in Caace1, similar to the ace1 mutation associated with triazophos resistance in C. suppressalis, was detected. Detailed examination of field populations of C. auricilius indicated this resistance mutation in C. auricilius is still quite infrequent. Based on the assay of AChE activity and RFLP-PCR testing, an individual that contains resistance mutation has lower AChE activities, while the individual that does not contain the resistance mutation has higher AChE activities. This study provides a basis for future investigations into the mechanism of OP resistance in C. auricilius, as well as a guidance for C. auricilius control with reasonable choice of pesticides.

Luo|Guang-Hua|GH| Li|Xiao-Huan|XH| Zhang|Zhi-Chun|ZC| Liu|Bao-Sheng|BS| Huang|Shui-Jin|SJ| Fang|Ji-Chao|JC|

acetylcholinesterase
point mutation
triazophos
resistance
Chilo auricilius


Genomic Prediction of Antimicrobial Resistance: Ready or Not, Here It Comes!

Abstract:
BACKGROUND
Next-generation sequencing (NGS) technologies are being used to predict antimicrobial resistance. The field is evolving rapidly and transitioning out of the research setting into clinical use. Clinical laboratories are evaluating the accuracy and utility of genomic resistance prediction, including methods for NGS, downstream bioinformatic pipeline components, and the clinical settings in which this type of testing should be offered.

CONTENT
We describe genomic sequencing as it pertains to predicting antimicrobial resistance in clinical isolates and samples. We elaborate on current methodologies and workflows to perform this testing and summarize the current state of genomic resistance prediction in clinical settings. To highlight this aspect, we include 3 medically relevant microorganism exemplars: Mycobacterium tuberculosis, Staphylococcus aureus, and Neisseria gonorrhoeae. Last, we discuss the future of genomic-based resistance detection in clinical microbiology laboratories.

SUMMARY
Antimicrobial resistance prediction by genomic approaches is in its infancy for routine patient care. Genomic approaches have already added value to the current diagnostic testing landscape in specific circumstances and will play an increasingly important role in diagnostic microbiology. Future advancements will shorten turnaround time, reduce costs, and improve our analysis and interpretation of clinically actionable results.

Ransom|Eric M|EM|
Potter|Robert F|RF|
Dantas|Gautam|G|
Burnham|Carey-Ann D|CD|

Sequencing
NGS
Resistance Prediction
Clinical Microbiology
Drug Prediction
Nanopore
Resistance Genes
Review
Susceptibility Testing
WGS


Burden and risk factors of diabetes and hyperglycemia in India: findings from the Global Burden of Disease Study 2016.

Abstract:
Background
Diabetes, hyperglycemia, and their complications are a growing problem in India. However, no comprehensive picture of this disease burden has yet been presented to date.

Methods
I used aggregate data from the Global Burden of Disease 2016 to describe the burden of diabetes and its risk factors, chronic kidney disease (CKD) due to diabetes, and diseases caused by high fasting plasma glucose from 1990 to 2016 in India.

Results
Deaths due to diabetes accounted for 3.1% (95% uncertainty interval [UI]: 2.9-3.3) of all deaths in India in 2016, up from 0.98% (95% UI: 0.87-1.1) of all deaths in 1990. Diabetes and hyperglycemia accounted for 27.5 million disability-adjusted life years in 2016, of which diabetes accounted for 10 million. Diabetes contributes to the causation of ischemic heart disease, stroke, CKD, peripheral artery disease, specific cancers, and tuberculosis via intermediate hyperglycemia. High body mass index, dietary factors (diet low in fruits, nuts and seeds, and whole grains), and tobacco use were the most important risk factors for diabetes.

Conclusion
Diabetes and CKD due to hyperglycemia pose a large and increasing burden in India. Urgent programs and policies are needed to reduce the identified risk factors for diabetes and its burden.

diabetes
hyperglycemia
chronic kidney disease
ischemic heart disease
tuberculosis
morbidity
mortality


HIV Testing and Entry to Care Among Trans Women in Indiana.

Abstract: Trans women in the United States are disproportionately affected by HIV infection. To improve HIV services for this population, more information is needed about their experiences in early stages of the HIV Care Continuum. Trans women in states such as Indiana, which has moderate HIV incidence but little public health investment in HIV prevention and treatment, experience special challenges. Our qualitative descriptive study describes the circumstances influencing HIV testing and entry to care by 18 trans women living with HIV in Central Indiana. In-depth interviews regarding participants' HIV care experiences were analyzed using standard content analysis. Participants discussed three main topics: (a) HIV testing circumstances, (b) facilitators and barriers to entering care, and (c) motivators for entering care after a delay. Findings indicate that social relationships play a significant role in trans women's care experiences and that stigma, discrimination, and adverse life circumstance are powerful deterrents to care. Practice and policy implications are discussed.

Hines|Dana D|DD|
Draucker|Claire Burke|CB|
Habermann|Barbara|B|

D010342:Patient Acceptance of Health Care

HIV testing
trans women
HIV Care Continuum
HIV treatment
entry to HIV care


Melanopsin+RGCs Are fully Resistant to NMDA-Induced Excitotoxicity.

Abstract: We studied short- and long-term effects of intravitreal injection of N-methyl-d-aspartate (NMDA) on melanopsin-containing (m+) and non-melanopsin-containing (Brn3a+) retinal ganglion cells (RGCs). In adult SD-rats, the left eye received a single intravitreal injection of 5µL of 100nM NMDA. At 3 and 15 months, retinal thickness was measured in vivo using Spectral Domain-Optical Coherence Tomography (SD-OCT). Ex vivo analyses were done at 3, 7, or 14 days or 15 months after damage. Whole-mounted retinas were immunolabelled for brain-specific homeobox/POU domain protein 3A (Brn3a) and melanopsin (m), the total number of Brn3a+RGCs and m+RGCs were quantified, and their topography represented. In control retinas, the mean total numbers of Brn3a+RGCs and m+RGCs were 78,903 ± 3572 and 2358 ± 144 (mean ± SD; n = 10), respectively. In the NMDA injected retinas, Brn3a+RGCs numbers diminished to 49%, 28%, 24%, and 19%, at 3, 7, 14 days, and 15 months, respectively. There was no further loss between 7 days and 15 months. The number of immunoidentified m+RGCs decreased significantly at 3 days, recovered between 3 and 7 days, and were back to normal thereafter. OCT measurements revealed a significant thinning of the left retinas at 3 and 15 months. Intravitreal injections of NMDA induced within a week a rapid loss of 72% of Brn3a+RGCs, a transient downregulation of melanopsin expression (but not m+RGC death), and a thinning of the inner retinal layers.

D000818:Animals
D002452:Cell Count
D005260:Female
D058449:Intravitreal Injections
D016202:N-Methylaspartate
D017207:Rats, Sprague-Dawley
D016194:Receptors, N-Methyl-D-Aspartate
D012165:Retinal Ganglion Cells
D017299:Rod Opsins
D050819:Transcription Factor Brn-3A

excitotoxicity
NMDA
SD-OCT
retina
Brn3a+RGCs
adult albino rat
glaucoma
intrinsically photosensitive-RGCs
melanopsin-RGCs


Influences on formation of tetanus antibody after simultaneous injection of tetanus immunoglobulin with tetanus vaccine.

Abstract: The goal of this study was to determine how much the formation of tetanus antibody is influenced after a single injection of tetanus vaccine (Td) and the simultaneous injection of tetanus vaccine with tetanus immunoglobulin (TIG). All of the healthy adult volunteers were divided into two groups: group 1 (Td only) and group 2 (Td plus TIG). Two hundred thirty seven volunteers were enrolled. When the baseline antibody titer, gender and age were adjusted, the geometric mean titers (GMTs) of the tetanus antibody (group 1 vs group 2) was 0.8438 IU/mL vs 0.5684 IU/mL at 4 weeks (P = 0.002), 0.4074 IU/mL vs 0.3217 IU/mL at 6 months (P = 0.072) and 0.3398 IU/mL vs 0.2761 IU/mL at 12 months (P = 0.140) after injection, respectively. The formation of tetanus antibody after tetanus vaccination is not influenced by TIG at the late period and in adults below the age of 50 yr, but there are significant differences between the two groups at the early period of 4 weeks after vaccination and for the patients over 60 yr.


A randomized, controlled trial of magnetic therapy for carpal tunnel syndrome.

Abstract:
INTRODUCTION
Magnet therapy has been proposed as a treatment for neurologic conditions. In this this trial we assessed the feasibility and efficacy of a magnet inserted into a wristband for carpal tunnel syndrome (CTS).

METHODS
Twenty-two patients with mild to moderate CTS were randomized to wear a high-dose or low-dose "sham" magnetic wristband for 6 weeks. The primary outcome was the Symptom Severity Scale (SSS) of the Boston Carpal Tunnel Questionnaire. Secondary measures were nerve conduction studies (NCS), median nerve ultrasound, and compliance.

RESULTS
Compliance for both groups was >90%. Improvements in the mean SSS, NCS, and median nerve ultrasound did not reach statistical significance.

DISCUSSION
Magnet therapy via wristband is well-tolerated. Further investigations in larger populations are needed to determine efficacy. Muscle Nerve 58: 310-313, 2018.

Baute|Vanessa|V|
Keskinyan|Vahakn S|VS|
Sweeney|Erica R|ER|
Bowden|Kayla D|KD|
Gordon|Allison|A|
Hutchens|Janet|J|
Cartwright|Michael S|MS|

magnet therapy
carpal tunnel syndrome
median nerve ultrasound
alternative therapy for CTS
complementary therapy for CTS
static magnetic field


Which Regional Pain Rating Best Predicts Patient-Reported Improvement in Lumbar Radiculopathy?

Abstract:
OBJECTIVE
To determine the best regional pain score cutoff value that corresponds with patient-reported improvement in lumbosacral radiculopathy (LSR).

DESIGN
Retrospective pooled data analysis from 3 randomized, controlled, multicenter trials using similar outcome assessments. All participants were exposed to interventions (epidural injections).

SETTING
Military medical centers (6 U.S.A., 1 Germany) and large tertiary care hospitals (4 urban, 1 Veterans Affairs) between 2008 and 2014.

SUBJECTS
A total of 352 active duty military personnel and civilians ≥ 18 years of age with LSR.

METHODS
Receiver operating characteristics (ROC) with area under the curve (AUC) were calculated for 1-month outcomes for pain (numeric rating scale) using absolute and relative change in regional pain scores (back, leg) to predict clinical improvement (global perceived effect).

RESULTS
Leg pain demonstrated greater predictive ability to identify clinical improvement compared to back pain for both absolute (ROC AUC [95% confidence interval (CI)] 0.855 [0.813, 0.896] vs. 0.753 [0.702, 0.805]; P < 0.001) and relative (AUC [95% CI]; 0.867 [0.826, 0.909] vs. 0.780 [0.729, 0.831]; P = 0.002) reduction in reported pain. Clinical improvement was best identified using a leg pain reduction threshold of ≥ 1.75 points (absolute) and ≥ 23.5% (relative).

CONCLUSIONS
Region-specific pain cutoff ratings predicted clinical improvement for patients with LSR. Cutoff points using newly identified, smaller reductions of 1.75 points and 23.5% more accurately predicted clinical improvement for LSR than conventionally used cutoffs (2 points and 30%). LSR patients report meaningful clinical improvement with smaller reductions in pain compared to other chronic pain diagnoses, suggesting LSR patients may have different expectations.

Bicket|Mark C|MC|0000-0001-9406-5953
Pasquina|Paul F|PF|
Cohen|Steven P|SP|

epidural
back pain with radiation
pain measurement


Aberrant expression of miR-214 is associated with obesity-induced insulin resistance as a biomarker and therapeutic.

Abstract:
BACKGROUND
Insulin resistance (IR) in obesity is associated with the occurrence of metabolic and cardiovascular diseases. Dipepidyl peptidase 4 (DPP4) plays a pivotal role during the development of IR, and was found to be a target gene of microRNA-214 (miR-214) in our study. This study sought to assess the expression and clinical value of miR-214 in obese patients with IR, and investigate its therapeutic potential in obese rats and adipocytes with IR.

METHODS
Serum expression of miR-214 in obese patients with or without IR was estimated by quantitative real-time-PCR. A receiver operating characteristic curve was plotted to evaluate the diagnostic value of miR-214 in the patients. Obesity-induced IR animal and cell models were constructed, and the therapeutic ability of miR-214 was explored.

RESULTS
Serum expression of miR-214 was decreased in obese patients compared with the healthy controls, and the lowest expression was observed in the cases with IR. Downregulation of miR-214 was significantly correlated with the serum DPP4 levels and HOMA-IR of the patients upon IR conditions, and was demonstrated to perform diagnostic accuracy for distinguishing obese patients with IR from those without IR. In obesity-associated IR animal and cell models, the downregulation of miR-214 was also been detected. According to the measurement of glucose and insulin tolerance and glucose uptake abilities, we found that the overexpression of miR-214 could be used to alleviate IR in the IR models, especially when collaboratively used with DPP4 inhibitor vildagliptin.

CONCLUSION
All data revealed that miR-214, as a regulator of DPP4, is decreased in obese patients with IR and may serve as a diagnostic biomarker. The upregulation of miR-214 could improve IR in obese rats and adipocytes, indicating that miR-214 has the therapeutic potential for obesity and IR.

Cheng|Fangxiao|F| Yuan|Geheng|G| He|Jiao|J| Shao|Yimin|Y| Zhang|Junqing|J| Guo|Xiaohui|X|


Toxicokinetics and persistent thyroid hormone disrupting effects of chronic developmental exposure to chlorinated polyfluorinated ether sulfonate in Chinese rare minnow.

Abstract: The abnormality in thyroid hormone modulation in developmental fish, vulnerable to per- and polyfluorinated substances, is of particular concerns for the alternative substances. Juvenile rare minnows, were exposed to chlorinated polyfluoroalkyl ether sulfonates (Cl-PFESAs), the novel alternatives to perfluorooctane sulfonate (PFOS), for 4 weeks followed by 12 weeks of depuration. Half lives were determined to be 33 d, 29 d, and 47 d for total Cl-PFESAs, C8 Cl-PFESA and C10 Cl-PFESA, respectively. Preliminary toxicity test suggested that Cl-PFESAs are moderately toxic to Rare minnow with a LC50 of 20.8 mg/L (nominal concentration） after 96 h of exposure. In the chronic toxicity test, fishes were exposed to Cl-PFESAs at geometric mean measured concentrations of 86.5 μg/L, 162 μg/L and 329 μg/L. In juvenile fishes exposed to Cl-PFESAs for 4 weeks, gene profile sequencing analysis identified 3313 differentially expressed genes, based on which pathways regulating thyroid hormone synthesis and steroid synthesis were enriched. Both whole body total and free 3,5,3'-triiodothyronine (T3) levels were significantly increased. mRNA expression of genes regulating thyroid hormone synthesis (corticotropin-releasing hormone (CRH), thyroid-stimulating hormone (THS), sodium/iodide symporter (NIS), thyroglobulin (TG), and thyroid peroxidase (TPO), transport (transthyretin,TTR), deiodinase (Dio1, Dio2) and receptor (TRα and TRβ) were decreased. Uridinediphosphate glucoronosyl-transferases (UGT1A) gene, regulating THs metabolism, was also decreased. In adult fish, thyroid hormone and genes expression in hypothalamic-pituitary-thyroid axis remained at disturbed levels after 12 weeks of depuration without exposure. Chronic developmental exposure to Cl-PFESAs caused persistent thyroid hormone disrupting effects in fish, highlighting a necessity of comprehensive ecological risk assessment.

Liu|Wei|W| Yang|Jing|J| Li|Jingwen|J| Zhang|Jiangyu|J| Zhao|Jing|J| Yu|Dan|D| Xu|Yukang|Y| He|Xin|X| Zhang|Xin|X|

Toxicokinetics
Thyroid
Chronic toxicity
Per- and poly-fluorinated substances
RNA sequencing


Collective Trauma and Mental Health in Adolescents: A Retrospective Cohort Study of the Effects of Retraumatization.

Abstract: In the wake of the massive Canadian wildfire of May 2016 in the area of Fort McMurray Alberta, we observed increased rates of mental health problems, particularly post-traumatic stress disorder (PTSD), in school-aged adolescents (ages 11-19). Surprisingly, we did not see these rates decline over the 3.5-year follow-up period. Additionally, our research suggested that the impact of this mass incident resulted in other unanticipated effects, including the finding that children who were not present for and relatively unaffected by the wildfire showed a similar PTSD symptom profile to children more directly involved, suggesting some degree of spillover or stress contagion. A potential explanation for these high rates in individuals who were not present could be undiagnosed retraumatization in some of the students. To investigate this possibility, we compared two groups of students: those who reported the wildfire as their most significant trauma (n = 740) and those who had their most significant trauma prior to the wildfire (n = 295). Those with significant pre-existing trauma had significantly higher rates of both depression and PTSD symptoms, although, unexpectedly the groups exhibited no differences in anxiety level. Taken together, this evidence suggests retraumatization is both longer-lasting and more widespread than might be predicted on a case-by-case basis, suggesting the need to reconceptualize the role of past trauma history in present symptomatology. These findings point to the need to recognize that crises instigated by natural disasters are mass phenomena which expose those involved to numerous unanticipated risks. New trauma-informed treatment approaches are required that incorporate sensitivity to the collective impact of mass crises, and recognize the risk of poorer long-term mental health outcomes for those who experienced trauma in the past.

Pazderka|Hannah|H|
Brown|Matthew R G|MRG|
Agyapong|Vincent I O|VIO|
Greenshaw|Andrew James|AJ|
McDonald-Harker|Caroline Beth|CB|
Noble|Shannon|S|
Mankowski|Monica|M|
Lee|Bonnie|B|
Drolet|Julie L|JL|
Omeje|Joy|J|
Brett-MacLean|Pamela|P|
Kitching|Deborah Terry|DT|
Silverstone|Peter H|PH|

collective trauma
adolescent
retraumatization
post-traumatic stress disorder
stress contagion
sexual abuse trauma
trauma informed practice


The role of oxidative and nitrosative stress in accelerated aging and major depressive disorder.

Abstract: Major depressive disorder (MDD) affects millions of individuals and is highly comorbid with many age associated diseases such as diabetes mellitus, immune-inflammatory dysregulation and cardiovascular diseases. Oxidative/nitrosative stress plays a fundamental role in aging, as well as in the pathogenesis of neurodegenerative/neuropsychiatric disorders including MDD. In this review, we critically review the evidence for an involvement of oxidative/nitrosative stress in acceleration of aging process in MDD. There are evidence of the association between MDD and changes in molecular mechanisms involved in aging. There is a significant association between telomere length, enzymatic antioxidant activities (SOD, CAT, GPx), glutathione (GSH), lipid peroxidation (MDA), nuclear factor κB, inflammatory cytokines with MDD. Major depression also is characterized by significantly lower concentration of antioxidants (zinc, coenzyme Q10, PON1). Since, aging and MDD share a common biological base in their pathophysiology, the potential therapeutic use of antioxidants and anti-aging molecules in MDD could be promising.

Maurya|Pawan Kumar|PK|
Noto|Cristiano|C|
Rizzo|Lucas B|LB|
Rios|Adiel C|AC|
Nunes|Sandra O V|SO|
Barbosa|Décio Sabbatini|DS|
Sethi|Sumit|S|
Zeni|Maiara|M|
Mansur|Rodrigo B|RB|
Maes|Michael|M|
Brietzke|Elisa|E|

Accelerated aging
Major depressive disorder
Clinical implications
Oxidative stress


Identification of Androgen Receptor Metabolic Correlome Reveals the Repression of Ceramide Kinase by Androgens.

Abstract: Prostate cancer (PCa) is one of the most prevalent cancers in men. Androgen receptor signaling plays a major role in this disease, and androgen deprivation therapy is a common therapeutic strategy in recurrent disease. Sphingolipid metabolism plays a central role in cell death, survival, and therapy resistance in cancer. Ceramide kinase (CERK) catalyzes the phosphorylation of ceramide to ceramide 1-phosphate, which regulates various cellular functions including cell growth and migration. Here we show that activated androgen receptor (AR) is a repressor of CERK expression. We undertook a bioinformatics strategy using PCa transcriptomics datasets to ascertain the metabolic alterations associated with AR activity. CERK was among the most prominent negatively correlated genes in our analysis. Interestingly, we demonstrated through various experimental approaches that activated AR reduces the mRNA expression of CERK: (i) expression of CERK is predominant in cell lines with low or negative AR activity; (ii) AR agonist and antagonist repress and induce CERK mRNA expression, respectively; (iii) orchiectomy in wildtype mice or mice with PCa (harboring prostate-specific Pten deletion) results in elevated Cerk mRNA levels in prostate tissue. Mechanistically, we found that AR represses CERK through interaction with its regulatory elements and that the transcriptional repressor EZH2 contributes to this process. In summary, we identify a repressive mode of AR that influences the expression of CERK in PCa.

Camacho|Laura|L|
Zabala-Letona|Amaia|A|
Cortazar|Ana R|AR|
Astobiza|Ianire|I|
Dominguez-Herrera|Asier|A|
Ercilla|Amaia|A|0000-0001-8999-7131
Crespo|Jana|J|
Viera|Cristina|C|
Fernández-Ruiz|Sonia|S|
Martinez-Gonzalez|Ainara|A|
Torrano|Veronica|V|
Martín-Martín|Natalia|N|
Gomez-Muñoz|Antonio|A|
Carracedo|Arkaitz|A|0000-0001-5957-1260

ceramide kinase
prostate cancer
sphingolipid metabolism
bioinformatics
mouse models


Long-term renal outcomes in a cohort of 1814 Chinese patients with biopsy-proven lupus nephritis.

Abstract: In the present study, we observed the renal outcomes in a cohort of 1814 Chinese patients with biopsy-proven lupus nephritis (LN) and evaluated the risk factors associated with poor renal prognosis. The 5 -, 10 -, 15 - and 20-year renal survival rates were 93.1%, 87.9%, 81.0% and 68.3%, respectively. Gender, LN duration, mean arterial pressure (MAP), proteinuria, serum creatinine, haemoglobin and pathological classification at the time of biopsy were independent risk factors for end-stage renal disease (ESRD). The long-term renal outcomes of patients with class II LN were unfavorable as opposed to those with class V. Additionally, the time-average proteinuria (TA-Pro) and the time-average mean arterial pressure (TA-MAP) during the follow-up were important risk factors for ESRD, with better predictive values than the baseline proteinuria and MAP. The results underscore the need for proteinuria and blood pressure control during follow-up in patients with LN; proteinuria levels should be controlled at least to < 1.0 g/24 h, and optimally to < 0.5 g/24 h; MAP should not exceed 96.5 mmHg. More attention should be paid to class II LN and emphasis should be placed on recurrence prevention of class II LN.

Yang|J|J| Liang|D|D| Zhang|H|H| Liu|Z|Z| Le|W|W| Zhou|M|M| Hu|W|W| Zeng|C|C| Liu|Z|Z|

renal outcome
Lupus nephritis
risk factor
time-average proteinuria
time-average mean arterial pressure


The nature of hematite depression with corn starch in the reverse flotation of iron ore.

Abstract: The function of corn starch and the significance of the order of addition of corn starch and mono ether amine in the reverse flotation of iron ore has been investigated. Understanding hematite depression with starch and the corresponding hydrophilic state involves consideration of adsorption with amine as well as flocculation of fine hematite. Captive bubble contact angle and micro-flotation experiments indicated that amine has an affinity towards both hematite and quartz, and that the role of starch is to hinder the adsorption of amine at the hematite surface so that flotation is inhibited. Micro-flotation results confirmed that quartz does not have affinity towards starch at pH 10.5. In addition to competitive adsorption, flocculation of fine hematite occurs and images from high resolution X-ray computed tomography (HRXCT) and cryo-SEM reveal further detail regarding floc structure. These results provide substantial evidence that the fine hematite particles are flocculated in the presence of corn starch, and flocculation is dependent on the particle size of hematite, with greater flocculation for finer particles. Thus, starch is playing a dual role in the reverse flotation of iron ore, acting as a depressant by hindering amine adsorption at the hematite surface in order to maintain the hydrophilic surface state of hematite, and acting as a flocculant to aggregate fine hematite particles, which if not flocculated, could diminish the flotation separation efficiency by being transported to the froth phase during reverse flotation.

Shrimali|Kaustubh|K|
Atluri|Venkata|V|
Wang|Yan|Y|
Bacchuwar|Sanket|S|
Wang|Xuming|X|
Miller|Jan D|JD|

High resolution X-ray micro tomography (HRXCT)


Laser-Induced Periodic Surface Structuring of Poly(trimethylene terephthalate) Films Containing Tungsten Disulfide Nanotubes.

Abstract: We report the study of the formation of Laser Induced Periodic Surface Structures (LIPSS), with UV femtosecond laser pulses (λ = 265 nm), in free-standing films of both Poly(trimethylene terephthalate) (PTT) and the composite PTT/tungsten disulfide inorganic nanotubes (PTT-WS2). We characterized the range of fluences and number of pulses necessary to induce LIPSS formation and measured the topography of the samples by Atomic Force Microscopy, the change in surface energy and contact angle using the sessile drop technique, and the modification in both Young's modulus and adhesion force values with Peak Force-Quantitative Nanomechanical Mapping. LIPSS appeared parallel to the laser polarization with a period close to its wavelength in a narrow fluence and number of pulses regime, with PTT-WS2 needing slightly larger fluence than raw PTT due to its higher crystallinity and heat diffusion. Little change was found in the total surface energy of the samples, but there was a radical increase in the negative polar component (γ-). Besides, we measured small variations in the samples Young's modulus after LIPSS formation whereas adhesion is reduced by a factor of four. This reduction, as well as the increase in γ-, is a result of the modification of the surface chemistry, in particular a slight oxidation, during irradiation.

Prada-Rodrigo|Javier|J|
Rodríguez-Beltrán|René I|RI|
Paszkiewicz|Sandra|S|
Szymczyk|Anna|A|
Ezquerra|Tiberio A|TA|
Moreno|Pablo|P|
Rebollar|Esther|E|

LIPSS
laser material processing
nanocomposites
nanostructures
ultrashort pulses


Fever: suppress or let it ride?

Abstract: While our ability to detect and manage fever has evolved since its conceptualization in the 5(th) century BC, controversy remains over the best evidence-based practices regarding if and when to treat this physiologic derangement in the critically ill. There are two basic fields of thought: (I) fever should be suppressed because its metabolic costs outweigh its potential physiologic benefit in an already stressed host; vs. (II) fever is a protective adaptive response that should be allowed to run its course under most circumstances. The latter approach, sometime referred to as the "let it ride" philosophy, has been supported by several recent randomized controlled trials like that of Young et al. [2015], which are challenging earlier observational studies and may be pushing the pendulum away from the Pavlovian treatment response.

Critical care
ICU
acetaminophen
febrile
infection


Suppressors of RNAi from plant viruses are subject to episodic positive selection.

Abstract: Viral suppressors of RNAi (VSRs) are proteins that actively inhibit the antiviral RNA interference (RNAi) immune response, providing an immune evasion route for viruses. It has been hypothesized that VSRs are engaged in a molecular 'arms race' with RNAi pathway genes. Two lines of evidence support this. First, VSRs from plant viruses display high sequence diversity, and are frequently gained and lost over evolutionary time scales. Second, Drosophila antiviral RNAi genes show high rates of adaptive evolution. Here, we investigate whether VSRs diversify faster than other genes and, if so, whether this is a result of positive selection, as might be expected in an arms race. By analysis of 12 plant RNA viruses, we show that the relative rate of protein evolution is higher for VSRs than for other genes, but that this is not attributable to pervasive positive selection. We argue that, because evolutionary time scales are extremely different for viruses and eukaryotes, it is improbable that viral adaptation (as measured by the ratio of non-synonymous to synonymous change) will be dominated by one-to-one coevolution with eukaryotes. Instead, for plant virus VSRs, we find strong evidence of episodic selection--diversifying selection that acts on a subset of lineages--which might be attributable to frequent shifts between different host genotypes or species.

Murray|Gemma G R|GG|
Kosakovsky Pond|Sergei L|SL|
Obbard|Darren J|DJ|

D000818:Animals
D000998:Antiviral Agents
D019143:Evolution, Molecular
D010802:Phylogeny
D010942:Plant Viruses
D034622:RNA Interference
D012328:RNA Viruses
D012641:Selection, Genetic
D014764:Viral Proteins

positive selection
viral suppressor of RNAi
RNA interference
RNA silencing suppressors
evolutionary arms race
molecular evolution


Health Monitoring of Bolted Spherical Joint Connection Based on Active Sensing Technique Using Piezoceramic Transducers.

Abstract: Bolted spherical joints are widely used to form space steel structures. The stiffness and load capacity of the structures are affected by the looseness of bolted spherical joint connections in the structures. The looseness of the connections, which can be caused by fabrication error, low modeling accuracy, and "false twist" in the installation process, may negatively impact the load capacity of the structure and even lead to severe accidents. Furthermore, it is difficult to detect bolted spherical joint connection looseness from the outside since the bolts connect spheres with rods together from the inside. Active sensing methods are proposed in this paper to monitor the tightness status of the bolted spherical connection using piezoceramic transducers. A triangle-on-triangle offset grid composed of bolted spherical joints and steel tube bars was fabricated as the specimen and was used to validate the active sensing methods. Lead Zirconate Titanate (PZT) patches were used as sensors and actuators to monitor the bolted spherical joint tightness status. One PZT patch mounted on the central bolted sphere at the upper chord was used as an actuator to generate a stress wave. Another PZT patch mounted on the bar was used as a sensor to detect the propagated waves through the bolted spherical connection. The looseness of the connection can impact the energy of the stress wave propagated through the connection. The wavelet packet analysis and time reversal (TR) method were used to quantify the energy of the transmitted signal between the PZT patches by which the tightness status of the connection can be detected. In order to verify the effectiveness, repeatability, and consistency of the proposed methods, the experiments were repeated six times in different bolted spherical connection positions. The experimental results showed that the wavelet packet analysis and TR method are effective in detecting the tightness status of the connections. The proposed active monitoring method using PZT transducers can monitor the tightness levels of bolted spherical joint connections efficiently and shows its potential to guarantee the safety of space steel structures in construction and service.

Xu|Jing|J| Wang|Chenyu|C| Li|Hongnan|H| Zhang|Chunwei|C| Hao|Jiajia|J| Fan|Shuli|S|0000-0003-4081-0414

bolted spherical joint connection
active sensing technique
space steel structures
tightness status
Lead Zirconate Titanate (PZT)
wavelet packet analysis
time reversal method


Effects of Xiaoshuan enteric-coated capsule on neurovascular functions assessed by quantitative multiparametric MRI in a rat model of permanent cerebral ischemia.

Abstract:
BACKGROUND
Buyang Huanwu Decoction (BYHWD) is a Traditional Chinese Medicine (TCM) formula for treating stroke-induced disability. Xiaoshuan enteric-coated capsule (XSECC), derived from the formula BYHWD, is a drug approved by the China Food and Drug Administration (CFDA) for stroke management. To further investigate the potential protective effects of XSECC on neurovascular functions, we endeavour to monitor the neurovascular functions using multimodal magnetic resonance imaging (MRI) and evaluated histopathological changes of neurovascular unit (NVU) after stroke.

METHODS
Ischemic stroke was induced by permanent middle cerebral artery occlusion (pMCAO). XSECC (420 mg/kg) was orally administered 2 h after stroke and daily thereafter. T2-weighted imaging (T2WI), T2 relaxometry mapping and diffusion tensor imaging (DTI) were used to measure cerebral infarct volume, edema and white matter fiber integrity, respectively. Neurochemical metabolite levels were monitored by (1)H-magnetic resonance spectroscopy ((1)H-MRS). Arterial spin labeling (ASL) - cerebral blood flow (CBF) measurements and structural magnetic resonance angiography (MRA) images provided real-time and dynamic information about vascular hemodynamic dysfunction on the 3rd, 7th and 14th days after pMCAO. At the last imaging time point, immunohistochemistry, immunofluorescence as well as transmission electron microscopy (TEM) were used to test the microscopic and ultrastructural changes of NVU.

RESULTS
T2WI, T2 relaxometry mapping and Fractional anisotropy (FA) in DTI showed that XSECC significantly reduced cerebral infarct volume, relieved edema and alleviated nerve fiber injuries, respectively. (1)H-MRS provided information about improvement of neuronal/glial metabolism after XSECC treatment. Moreover, ASL - CBF measurements combined with MRA showed that XSECC significantly increased CBF and vascular signal strength and alleviated ischemia-induced morphological changes of arteries in ischemic hemisphere within 14 days after stroke. In addition, neuron specific nuclear protein (NeuN), glial fibrillary acidic protein (GFAP), CD34 staining and TEM detection indicated that XSECC not only ameliorated neuronal injury, but also reduced endothelial damage and inhibited astrocyte proliferation.

CONCLUSIONS
Our results suggested that XSECC has multi-target neurovascular protective effects on ischemic stroke, which may be closely correlated with the improvement of cerebral blood supply and neuronal/glial metabolism.

D000818:Animals
D001929:Brain Edema
D002214:Capsules
D002544:Cerebral Infarction
D002560:Cerebrovascular Circulation
D004195:Disease Models, Animal
D004365:Drugs, Chinese Herbal
D008279:Magnetic Resonance Imaging
D008297:Male
D009412:Nerve Fibers
D018696:Neuroprotective Agents
D051381:Rats
D017207:Rats, Sprague-Dawley

Xiaoshuan enteric-coated capsule
Magnetic resonance image
Neurovascular unit
Ischemic stroke
Middle cerebral artery occlusion
Cerebral blood flow


Interstrain differences in the progression of nonalcoholic steatohepatitis to fibrosis in mice are associated with altered hepatic iron metabolism.

Abstract: Nonalcoholic fatty liver disease (NAFLD) is a major health problem worldwide. Currently, there is a lack of conclusive information to clarify the molecular events and mechanisms responsible for the progression of NAFLD to fibrosis and cirrhosis and, more importantly, for differences in interindividual disease severity. The aim of this study was to investigate a role of interindividual differences in iron metabolism among inbred mouse strains in the pathogenesis and severity of fibrosis in a model of NAFLD. Feeding male A/J, 129S1/SvImJ and WSB/EiJ mice a choline- and folate-deficient diet caused NAFLD-associated liver injury and iron metabolism abnormalities, especially in WSB/EiJ mice. NAFLD-associated fibrogenesis was correlated with a marked strain- and injury-dependent increase in the expression of iron metabolism genes, especially transferrin receptor (Tfrc), ferritin heavy chain (Fth1), and solute carrier family 40 (iron-regulated transporter), member 1 (Slc40a1, Fpn1) and their related proteins, and pronounced down-regulation of the iron regulatory protein 1 (IRP1), with the magnitude being A/J<129S1/SvImJ<WSB/EiJ. Mechanistically, down-regulation of IRP1 was linked to an increased expression of microRNAs miR-200a and miR-223, which was negatively correlated with IRP1. The results of this study demonstrate that the interstrain variability in the extent of fibrogenesis was associated with a strain-dependent deregulation of hepatic iron homeostasis.

Shpyleva|Svitlana|S|
Pogribna|Marta|M|
Cozart|Christy|C|
Bryant|Matthew S|MS|
Muskhelishvili|Levan|L|
Tryndyak|Volodymyr P|VP|
Ross|Sharon A|SA|
Beland|Frederick A|FA|
Pogribny|Igor P|IP|

D065626:Non-alcoholic Fatty Liver Disease

Iron metabolism
NAFLD
IRP1
miR-200a
Liver fibrogenesis
Methyl-deficient diet


Sonochemical effect of flat sweep frequency and pulsed ultrasound (FSFP) treatment on stability of phenolic acids in a model system.

Abstract: To obtain greater knowledge on the stability of phenolic acids for the application of FSFP ultrasound technique in the extraction, the sonochemical effects of ultrasonic factors were investigated. The kinetic model and mechanism of degradation reaction were developed and identified by FT-IR and HPLC-ESIMS. The results showed that caffeic and sinapic acids were degraded under FSFP ultrasound treatment. The ultrasonic temperature, frequency, sweep range, sweep cycle, and pulse ratio were proved to be important factors in affecting the degradation rates of caffeic and sinapic acids. Relatively high temperature, frequency away from the resonance frequency, narrow sweep range, moderate sweep cycle, and relatively low or high pulse ratio were recommended to maintain high stability of caffeic and sinapic acids. The degradation kinetics of these two phenolic acids under FSFP ultrasound treatment were conformed to zeroth-order reaction at 10-50°C. Moreover, FSFP ultrasound had a stronger sonochemical effect on sinapic acid than caffeic acid. The FT-IR and HPLC-ESIMS proved that decomposition and polymerization reactions occurred when caffeic and sinapic acids were subjected to FSFP ultrasound. Degradation products, such as the corresponding decarboxylation products and their dimers, were tentatively identified.

Wang|Juan|J| Ma|Haile|H| Pan|Zhongli|Z| Qu|Wenjuan|W|

Ultrasound
Stability
Phenolic acids
Kinetics
Mechanism
Degradation


Early Detection of Infusion Set Failure During Insulin Pump Therapy in Type 1 Diabetes.

Abstract:
BACKGROUND
Insulin infusion set failure resulting in prolonged hyperglycemia or diabetic ketoacidosis can occur with pump therapy in type 1 diabetes. Set failures are frequently characterized by variable and unpredictable patterns of increasing glucose values despite increased insulin infusion. Early detection may minimize the risk of prolonged hyperglycemia, an important consideration for automated insulin delivery and closed-loop applications.

METHODS
A novel algorithm designed to alert the patient to the onset of infusion set failure was developed based upon continuous glucose sensor values and insulin delivered from an insulin pump. The method was calibrated on 12 weeks of infusion set wear without failures recorded by 4 patients in ambulatory conditions and prospectively validated on 18 weeks of infusion set wear with and without failures belonging to 9 other subjects in ambulatory conditions.

RESULTS
The algorithm, evaluated retrospectively, identified a failure 2.52 ± 1.91 days ahead of the actual event as recorded by the clinical team, corresponding to 50% sensitivity, 66% specificity and 55% accuracy. If set failure alarms had been activated in real time, the average time >180 mg/dl would be reduced from 82.7 ± 40.9 hours/week/subject (without alarm) to 58.8 ± 31.1 hours/week/subject (with alarm), corresponding to a potential 29% reduction in time spent >180mg/dl.

CONCLUSION
The proposed method for early detection of infusion set failure based on glucose sensor and insulin data demonstrated favorable results on retrospective data and may be implemented as an additional safeguard in a future fully automated closed-loop system.

Cescon|Marzia|M|
DeSalvo|Daniel J|DJ|
Ly|Trang T|TT|
Maahs|David M|DM|
Messer|Laurel H|LH|
Buckingham|Bruce A|BA|
Doyle|Francis J|FJ|
Dassau|Eyal|E|

infusion set failures
artificial pancreas


Comparative analysis of micro-RNAs in human papillomavirus-positive versus -negative oropharyngeal cancers.

Abstract:
BACKGROUND
Oncogenic mechanisms of human papillomavirus (HPV)-positive oropharyngeal cancer are still poorly characterized. Analysis of their microRNA expression profile might provide valuable information.

METHODS
The microRNA expression profiles were analyzed by micro-arrays in 26 oropharyngeal cancers. A microRNA signature specific to HPV-status was identified by analyzing a learning/training set consisting of 16 oropharyngeal cancers. The robustness of this signature was further confirmed by blind case-by-case classification of a validation set composed of 10 independent tumors. Putative targeted molecular pathways were proposed using DIANA miRPath online software (http://microrna.gr/mirpath).

RESULTS
We have identified 25 miRNA signatures, which discriminates HPV16-positive oropharyngeal cancer from their HPV-negative counterparts. These 25 microRNAs play a potential role in Wnt and PI3K-pathways, cell-adhesion/cell-polarity, and the cytoskeleton regulation.

CONCLUSION
Our study contributes to a better understanding of pathogenic mechanisms involved in the development of HPV-positive oropharyngeal cancer and in the identification of potential therapeutic molecular targets. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1708-1716, 2016.

Mirghani|Haitham|H|
Ugolin|Nicolas|N|
Ory|Catherine|C|
Goislard|Maud|M|
Lefèvre|Marine|M|
Baulande|Sylvain|S|
Hofman|Paul|P|
Guily|Jean Lacau St|JL|
Chevillard|Sylvie|S|
Lacave|Roger|R|

PI3K pathway
Wnt pathway
gene expression profile
human papillomavirus 16
micro/miRNA
microarray
oropharyngeal/oropharynx cancer


Directed optimization of a newly identified squalene synthase from Mortierella alpine based on sequence truncation and site-directed mutagenesis.

Abstract: Terpenoids, a class of isoprenoids usually isolated from plants, are always used as commercial flavor and anticancer drugs. As a key precursor for triterpenes and sterols, biosynthesis of squalene (SQ) can be catalyzed by squalene synthase (SQS) from two farnesyl diphosphate molecules. In this work, the key SQS gene involved in sterols synthesis by Mortierella alpine, an industrial strain often used to produce unsaturated fatty acid such as γ-linolenic acid and arachidonic acid, was identified and characterized. Bioinformatic analysis indicated that MaSQS contained 416 amino acid residues involved in four highly conserved regions. Phylogenetic analysis revealed the closest relationship of MaSQS with Ganoderma lucidum and Aspergillus, which also belonged to the member of the fungus. Subsequently, the recombinant protein was expressed in Escherichia coli BL21(DE3) and detected by SDS-PAGE. To improve the expression and solubility of protein, 17 or 27 amino acids in the C-terminal were deleted. In vitro activity investigation based on gas chromatography-mass spectrometry revealed that both the truncated enzymes could functionally catalyze the reaction from FPP to SQ and the enzymatic activity was optimal at 37 °C, pH 7.2. Moreover, based on the site-directed mutagenesis, the mutant enzyme mMaSQSΔC17 (E186K) displayed a 3.4-fold improvement in catalytic efficiency (k(cat)/K(m)) compared to the control. It was the first report of characterization and modification of SQS from M. alpine, which facilitated the investigation of isoprenoid biosynthesis in the fungus. The engineered mMaSQSΔC17 (E186K) can be a potential candidate of the terpenes and steroids synthesis employed for synthetic biology.

Huang|Di|D| Yao|Yongpeng|Y| Zhang|Hang|H| Mei|Zhu|Z| Wang|Ru|R| Feng|Lu|L| Liu|Bin|B|

Squalene synthase
Mortierella alpine
Site-directed mutagenesis
Truncated enzyme
GC–MS analysis


Guanidinylated block copolymers for gene transfer: A comparison with amine-based materials for in vitro and in vivo gene transfer efficiency.

Abstract: There is currently no cure for neuron loss in the brain, which can occur due to traumatic injury or neurodegenerative disease. One proposed method to enhance brain neurogenesis is gene transfer to neural progenitor cells. In this work, a guanidine-based copolymer was synthesized and compared to an amine-based copolymer analog previously shown to effectively deliver genes in the murine brain. The guanidine-based copolymer was more efficient at gene transfer to immortalized, cultured cell lines; however, the amine-based copolymer was more effective at gene transfer in the brain. DNA condensation studies revealed that the nucleic acid complexes formed with the guanidine-based copolymer were more susceptible to unpackaging in the presence of anionic proteoglycans compared to complexes formed with the amine-based copolymer. Therefore, polyplexes formed from the amine-based copolymer may be more resistant to destabilization by the heparan sulfate proteoglycans present in the stem cell niches of the brain.

Choi|Jennifer L|JL|
Tan|James-Kevin Y|JK|
Sellers|Drew L|DL|
Wei|Hua|H|
Horner|Philip J|PJ|
Pun|Suzie H|SH|


Use of the ETView Tracheoscopic Ventilation Tube in airway management of a patient with unanticipated difficult bag-mask ventilation.

Abstract: The management of unanticipated difficult airway is a clinical challenge to anesthesiologists. The ETView Tracheoscopic Ventilation Tube (ETView), which is capable of real-time video imaging of the airway without needing additional equipment, may provide a promising settlement for the cases. Here, we reported a successful management of unanticipated difficult bag-mask ventilation airway with the ETView. More importantly, we successfully maintained oxygenation by modifying its injection and suction port.

Tracheoscopic Ventilation Tube
Airway management
Intratracheal
Intubation
Obstructive sleep apnea


Monoclonal antibodies and toxins--a perspective on function and isotype.

Abstract: Antibody therapy remains the only effective treatment for toxin-mediated diseases. The development of hybridoma technology has allowed the isolation of monoclonal antibodies (mAbs) with high specificity and defined properties, and numerous mAbs have been purified and characterized for their protective efficacy against different toxins. This review summarizes the mAb studies for 6 toxins--Shiga toxin, pertussis toxin, anthrax toxin, ricin toxin, botulinum toxin, and Staphylococcal enterotoxin B (SEB)--and analyzes the prevalence of mAb functions and their isotypes. Here we show that most toxin-binding mAbs resulted from immunization are non-protective and that mAbs with potential therapeutic use are preferably characterized. Various common practices and caveats of protection studies are discussed, with the goal of providing insights for the design of future research on antibody-toxin interactions.

antibody
isotype
protection
therapeutics
animal model
clearance
disease enhancement
in vivo
neutralization
vaccine


Hippocampal atrophy on MRI is predictive of histopathological patterns and surgical prognosis in mesial temporal lobe epilepsy with hippocampal sclerosis.

Abstract:
PURPOSE
To correlate hippocampal volumes obtained from brain structural imaging with histopathological patterns of hippocampal sclerosis (HS), in order to predict surgical outcome.

METHODS
Patients with mesial temporal lobe epilepsy (MTLE) with HS were selected. Clinical data were assessed pre-operatively and surgical outcome in the first year post surgery. One block of mid hippocampal body was selected for HS classification according to ILAE criteria. NeuN-immunoreactive cell bodies were counted within hippocampal subfields, in four randomly visual fields, and cell densities were transformed into z-score values. FreeSurfer processing of 1.5T brain structural images was used for subcortical and cortical volumetric estimation of the ipsilateral hippocampus. Univariate analysis of variance and Pearson's correlation test were applied for statistical analyses.

RESULTS
Sixty-two cases (31 female, 32 right HS) were included. ILAE type 1 HS was identified in 48 patients, type 2 in eight, type 3 in two, and four had no-HS. Better results regarding seizure control, i.e. ILAE 1, were achieved by patients with type 1 HS (58.3%). Patients with types 1 and 2 had smaller hippocampal volumes compared to those with no-HS (p<0.001 and p=0.004, respectively). Positive correlation was encountered between hippocampal volumes and CA1, CA3, CA4, and total estimated neuronal densities. CA2 was the only sector which did not correlate its neuronal density with hippocampal volume (p=0.390).

CONCLUSION
This is the first study correlating hippocampal volume on MRI submitted to FreeSurfer processing with ILAE patterns of HS and neuronal loss within each hippocampal subfield, a fundamental finding to anticipate surgical prognosis for patients with drug-resistant MTLE and HS.

Garcia|Maria Teresa Fernandes Castilho|MT|

Hippocampal atrophy
Mesial temporal lobe epilepsy
Hippocampal sclerosis
Surgical outcome
FreeSurfer analysis