In vitro antioxidant potential and in vivo effects of Schinus terebinthifolia Raddi leaf extract in diabetic rats and determination of chemical composition by HPLC-ESI-MS/MS.

Abstract: The present study investigated the in vitro and in vivo antioxidant potential and phytochemical composition of Schinus terebinthifolia, which is widely used in folk medicine for various therapeutic purposes. The in vitro analyses indicated that the hydroethanolic extract (HE) had 312.50 ± 0.50 mg GAE/g of total phenols. It also presented anti-DPPH• and anti-ABTS•+ activity, reduced phosphomolybden and metal ions and blocked the bleaching of β-carotene. The HE at concentrations of 3.0 and 2.0 μg/mL had TRAP values of 2.223 ± 0.018 and 1.894 ± 0.026 μM Trolox, respectively. The HE increased the availability of antioxidants in plasma in treated animals in vivo. HPLC-ESI-MS/MS indicated the presence of 11 phenols: cumaric acid, (+)-catechin, myricetin-3-O-glicuronide, kaempferol-3-O-glucoside, myricetin, myricitrin, quercetin, gallic acid, methyl galate, pentagalloyl glucose and ethyl galate. Thus, S. terebinthifolia has potential for the prevention or treatment of diseases that are related to oxidative stress, such as diabetes mellitus.

Ferreira|Lilian Dos Anjos Oliveira|LDAO|

D002851:Chromatography, High Pressure Liquid

D021241:Spectrometry, Mass, Electrospray Ionization

oxidative stress
Diabetes mellitus
medicinal plants
phenolic compounds


BMAL1 regulates mitochondrial fission and mitophagy through mitochondrial protein BNIP3 and is critical in the development of dilated cardiomyopathy.

Abstract: Dysregulation of circadian rhythms associates with cardiovascular disorders. It is known that deletion of the core circadian gene Bmal1 in mice causes dilated cardiomyopathy. However, the biological rhythm regulation system in mouse is very different from that of humans. Whether BMAL1 plays a role in regulating human heart function remains unclear. Here we generated a BMAL1 knockout human embryonic stem cell (hESC) model and further derived human BMAL1 deficient cardiomyocytes. We show that BMAL1 deficient hESC-derived cardiomyocytes exhibited typical phenotypes of dilated cardiomyopathy including attenuated contractility, calcium dysregulation, and disorganized myofilaments. In addition, mitochondrial fission and mitophagy were suppressed in BMAL1 deficient hESC-cardiomyocytes, which resulted in significantly attenuated mitochondrial oxidative phosphorylation and compromised cardiomyocyte function. We also found that BMAL1 binds to the E-box element in the promoter region of BNIP3 gene and specifically controls BNIP3 protein expression. BMAL1 knockout directly reduced BNIP3 protein level, causing compromised mitophagy and mitochondria dysfunction and thereby leading to compromised cardiomyocyte function. Our data indicated that the core circadian gene BMAL1 is critical for normal mitochondria activities and cardiac function. Circadian rhythm disruption may directly link to compromised heart function and dilated cardiomyopathy in humans.

Li|Ermin|E| Li|Xiuya|X| Huang|Jie|J| Xu|Chen|C| Liang|Qianqian|Q| Ren|Kehan|K| Bai|Aobing|A| Lu|Chao|C|0000-0002-9484-6415 Qian|Ruizhe|R|0000-0002-5992-2902 Sun|Ning|N|0000-0002-7861-3646

D056930:ARNTL Transcription Factors
D000818:Animals
D002311:Cardiomyopathy, Dilated
D002460:Cell Line
D006801:Humans
D008565:Membrane Proteins
D051379:Mice
D018345:Mice, Knockout
D008929:Mitochondria, Heart
D063154:Mitochondrial Dynamics
D024101:Mitochondrial Proteins
D032383:Myocytes, Cardiac

dilated cardiomyopathy
circadian gene BMAL1
human embryonic stem cells
cardiomyocytes
mitochondria
cell differentiation


Stable, Heat-Conducting Phosphor Composites for High-Power Laser Lighting.

Abstract: Solid-state lighting using laser diodes is an exciting new development that requires new phosphor geometries to handle the greater light fluxes involved. The greater flux from the source results in more conversion and therefore more conversion loss in the phosphor, which generates self-heating, surpassing the stability of current encapsulation strategies used for light-emitting diodes, usually based on silicones. Here, we present a rapid method using spark plasma sintering (SPS) for preparing ceramic phosphor composites of the canonical yellow-emitting phosphor Ce-doped yttrium aluminum garnet (Ce:YAG) combined with a chemically compatible and thermally stable oxide, α-Al2O3. SPS allows for compositional modulation, and phase fraction, microstructure, and luminescent properties of ceramic composites with varying compositions are studied here in detail. The relationship between density, thermal conductivity, and temperature rise during laser-driven phosphor conversion is elucidated, showing that only modest densities are required to mitigate thermal quenching in phosphor composites. Additionally, the scattering nature of the ceramic composites makes them ideal candidates for laser-driven white lighting in reflection mode, where Lambertian scattering of blue light offers great color uniformity, and a luminous flux >1000 lm is generated using a single commercial laser diode coupled to a single phosphor element.

phosphor
laser lighting
solid-state lighting
spark plasma sintering
white light


Rare extraskeletal Ewing's sarcoma mimicking as adenocarcinoma of the sigmoid.

Abstract:
INTRODUCTION
Extraskeletal Ewing's sarcoma (EES) is a rare finding in comparison with Ewing's sarcoma of bone and usually manifests in young patients. However, even in older patients, one must consider the diagnosis.

PATIENTS AND METHODS
In this case, we describe a 52-year-old woman diagnosed with EES, mimicking as adenocarcinoma of the sigmoid.

RESULTS
The tumor was not visualized by a multi-slice spiral computed tomography of the abdomen and pelvis with intravenous contrast, and eventually the diagnosis was made by positive immunohistochemical staining for CD99 and by molecular testing for EWSR1 translocation.

CONCLUSIONS
This combination of the patient's age and the localization of the tumor mimicking an adenocarcinoma of the sigmoid has never been described before.

Mertens|Michelle|M|
Haenen|Filip W N|FW|
Siozopoulou|Vasiliki|V|
Van Cleemput|Marc|M|

Ewing’s sarcoma
Extraskeletal Ewing’s sarcoma
abdominal surgery
general surgery


Hydrogen peroxide in neutrophil inflammation: Lesson from the zebrafish.

Abstract: The zebrafish has become an excellent model for the study of inflammation and immunity. Its unique advantages for in vivo imaging and gene and drug screening have allowed the visualization of dual oxidase 1 (Duox1)-derived hydrogen peroxide (H2O2) tissue gradients and its crosstalk with neutrophil infiltration to inflamed tissue. Thus, it has been shown that H2O2 directly recruits neutrophils via the Src-family tyrosine kinase Lyn and indirectly by the activation of several signaling pathways involved in inflammation, such as nuclear factor κB (NF-κB), mitogen activated kinases and the transcription factor AP1. In addition, this model has also unmasked the unexpected ability of H2O2 to induce the expression of the gene encoding the key neutrophil chemoattractant CXC chemokine ligand 8 by facilitating the accessibility of transcription factors to its promoter through histone covalent modifications. Finally, zebrafish models of psoriasis have shown that a H2O2/NF-κB/Duox1 positive feedback inflammatory loop operates in this chronic inflammatory disorder and that pharmacological inhibition of Duox1, but not of downstream mediators, inhibits inflammation and restores epithelial homeostasis. Therefore, these results have pointed out DUOX1 and H2O2 as therapeutic targets for the treatment of skin inflammatory disorders, such as psoriasis.

Martínez-Navarro|Francisco J|FJ|
Martínez-Morcillo|Francisco J|FJ|
de Oliveira|Sofia|S|
Candel|Sergio|S|
Cabas|Isabel|I|
García-Ayala|Alfonsa|A|
Martínez-Menchón|Teresa|T|
Corbalán-Vélez|Raúl|R|
Mesa-Del-Castillo|Pablo|P|
Cayuela|María L|ML|
Pérez-Oliva|Ana B|AB|
García-Moreno|Diana|D|
Mulero|Victoriano|V|

Hydrogen peroxide
Neutrophils
Inflammation
Psoriasis
Macrophages
Wounding


Stability indicating HPLC-UV method for detection of curcumin in Curcuma longa extract and emulsion formulation.

Abstract: A stability-indicating HPLC-UV method for the determination of curcumin in Curcuma longa extract and emulsion was developed. The system suitability parameters, theoretical plates (N), tailing factor (T), capacity factor (K'), height equivalent of a theoretical plate (H) and resolution (Rs) were calculated. Stress degradation studies (acid, base, oxidation, heat and UV light) of curcumin were performed in emulsion. It was found that N>6500, T<1.1, K' was 2.68-3.75, HETP about 37 and Rs was 1.8. The method was linear from 2 to 200 μg/mL with a correlation coefficient of 0.9998. The intra-day precision and accuracy for curcumin were ⩽0.87% and ⩽2.0%, while the inter-day precision and accuracy values were ⩽2.1% and ⩽-1.92. Curcumin degraded in emulsion under acid, alkali and UV light. In conclusion, the stability-indicating method could be employed to determine curcumin in bulk and emulsions.

Syed|Haroon Khalid|HK|
Liew|Kai Bin|KB|
Loh|Gabriel Onn Kit|GO|
Peh|Kok Khiang|KK|

Curcumin
System suitability
Stress degradation study
Stability indicating HPLC–UV method


Pinocembrin Ameliorates Cognitive Impairment Induced by Vascular Dementia: Contribution of Reelin-dab1 Signaling Pathway.

Abstract:
Background
As a substrate of apoER2, Reelin has been verified to exert neuroprotection by preventing memory impairment. Pinocembrin is the most abundant natural flavonoid found in propolis, and it has been used to exert neuroprotection, blood-brain barrier protection, anti-oxidation, and inflammation diminishing, both in vitro and in vivo. However, the roles and molecular mechanisms of pinocembrin in neurobehavioral outcomes and neuronal repair after vascular dementia are still under investigation.

Purpose
To explore the role of pinocembrin in the involvement of the Reelin-dab1 signaling pathway in improving memory impairment, both in cell culture and animals experiments.

Material and Methods
Behavioral tests were conducted on day 48 to confirm the protection of pinocembrin against cognitive impairment. Cell and molecular biology experiments demonstrated that the Reelin-dab1 pathway mediates the underlying mechanism of cognitive improvement by pinocembrin.

Results
It was showed that pinocembrin alleviated learning and memory deficits induced by vascular dementia, by inducing the expression of Reelin, apoER2, and p-dab1 in the hippocampus. The expression of Reelin and p-dab1 was both inhibited following Reelin RNA interference in SH-SY5Y prior to oxygen glucose deprivation (OGD) injury, suggesting that Reelin played a core role in pinocembrin's effect on OGD in vitro.

Conclusion
Pinocembrin improves the cognition via the Reelin-dab1 signaling pathway.

Kang|Ze-Chun|ZC| Wang|Hai-Gang|HG| Yang|Yu-Lin|YL| Zhao|Xiao-Yue|XY| Zhou|Qi-Meng|QM| Yang|Ying-Lin|YL| Yang|Jing-Yu|JY| Du|Guan-Hua|GH|

D048868:Adaptor Proteins, Signal Transducing

D015816:Cell Adhesion Molecules, Neuronal

pinocembrin
cognitive impairment
vascular dementia
signaling pathway
Reelin
hippocampus


Rapid identification of bacteria directly from positive blood cultures by a modified method using a serum separator tube and matrix-assisted laser desorption ionization - time of flight MS.

Abstract: Introduction. Several studies have used matrix-assisted laser desorption ionization-time of flight MS (MALDI-TOF) with a serum separator tube (SST) to perform rapid identification of microorganisms directly from positive blood cultures (BCs), with different performances and methodologies.Hypothesis / Gap Statement. The use of TSS could significantly reduce the time of identification of microorganisms that produce bacteremia.Aim. Our goals were to evaluate bacterial identification by MALDI-TOF using a method based on an SST and compare it with MALDI-TOF after subculture for 18-24 h.Methodology. BCs no more than 1 h after a positive growth signal were included in the study. Analysis of results was expressed as a score. Information about time to a positive signal and number of microorganisms was collected.Results. In total, 253 BCs were analysed; 45.5 % gave a reliable result, 23.3 % an unreliable result and 31.2 % an error in identification. In gram-negative and gram-positive bacteria, the percentages of reliable results were 83.5 and 21.8 %, respectively. According to time to positive signal, the percentages of correct identification and mean score were 81.1 % (99/122) and 1.89±0.30 in Group 1 (<15 h); and 57.2 % (75/131) and 1.70±0.32 in Group 2 (>15 h), respectively (P <0.001). According to the number of microorganisms, the corresponding percentages of correct identification and mean scores were: Group 1 [≤50 microorganisms observed per field (MOF)], 50/94 (53.19 %) and 1.72±0.32; Group 2 (51-100 MOF): 44/66 (66.67 %) and 1.85±0.34; Group 3 (>100 MOF): 79/93 (84.94 %) and 1.84±0.31.Conclusion. This method allowed us to obtain a high percentage of the aetiological agent of bacteraemia in less than 30 min after a positive BC.

Carretero|Octavio|O|
Rivas|Gonzalo|G|
Loras|Cristina|C|
Orellana|M Angeles|MA|

D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

blood culture
serum separator tube
MALDI-TOF
direct identification


Video therapy for atypical eating disorder and obesity: a case study.

Abstract: Both eating and weight disorders are prevalent in our society but many sufferers do not have access to specialist treatments, especially those living in remote and rural areas. Video therapy is proposed as a potential solution, allowing therapists to deliver psychological treatments without the costs associated with travel. Furthermore, there is a gap in the evidence base for those with co-morbid obesity and atypical eating disorders, but it is likely that treatments which focus on linking past and present patterns of behaviour and emphasise cognitive, behavioural and emotional change will be most effective. A naturalistic single case design was used to pilot the feasibility of providing video therapy using the schema therapy mode model, which involves a range of 'active' techniques including chair work and imagery. Results suggest that videoconferencing may be well suited to the delivery of experiential psychotherapy, leading to change across several domains. Scores on the EDE-Q showed a 77% improvement and the client was abstinent from vomiting during the last 28 days of treatment. The findings from this study indicate that video therapy may be effective for this co-morbid diagnostic group and highlight the need for further larger scale research.

video therapy
eating disorder
Obesity
schema therapy
single-case design.


A Method of FPGA-Based Extraction of High-Precision Time-Difference Information and Implementation of Its Hardware Circuit.

Abstract: Abstract: The positioning technology to find shallow underground vibration sources based on a wireless sensor network is receiving great interest in the field of underground position measurements. The slow peaking and strong multi-waveform aliasing typical of the underground vibration signal result in a low extraction accuracy of the time difference and a poor source-positioning accuracy. At the same time, the transmission of large amounts of sensor data and the host computer's slow data processing speed make locating a source a slow process. To address the above problems, this paper proposes a method for high-precision time-difference measurements in near-field blasting and a method for its hardware implementation. First, based on the broadband that is typical of blast waves, the peak frequency of the P-wave was obtained in the time-frequency domain, taking advantage of the difference in the propagation speed of the P-wave, S-wave, and the surface wave. Second, the phase difference between two sensor nodes was found by means of a spectral decomposition and a correlation measurement. Third, the phase ambiguity was eliminated using the time interval of the first break and the dynamic characteristics of the sensors. Finally, following a top-down design idea, the hardware system was designed using Field Programmable Gate Array(FPGA). Verification, using both numerical simulations and experiments, suggested that compared with generalized cross-correlation-based time-difference measurement methods, the proposed method produced a higher time-difference resolution and accuracy. Compared with the traditional host computer post-position positioning method, the proposed method was significantly quicker. It can be seen that the proposed method provides a new solution for solving high-precision and quick source-location problems, and affords a technical means for developing high-speed, real-time source-location instruments.

Li|Jian|J| Yan|Xinlei|X| Li|Maojin|M| Meng|Ming|M| Yan|Xin|X|

time difference
distributed source location
first break arrival time


Recurrent ACTG2 gene variation in African degenerative visceral leiomyopathy.

Abstract:
INTRODUCTION
Visceral myopathies remain difficult and frustrating clinical entities, a distinctive form of acquired degenerative visceral myopathy, African degenerative leiomyopathy, a myogenic functional intestinal obstruction without aganglionosis which affects smooth muscle of the intestine, in young indigenous African children. The Actin G2 gene is the main gene encoding smooth muscle actin found in enteric tissues. Recent research has identified Actin G2 alpha gene variation as an important causative biomarker in visceral myopathies and megacystis microcolon. This study of the Actin G2 gene (ACTG2) in an African population explores a possible molecular basis abnormal muscle function in a visceral myopathy.

PATIENTS AND METHODS
Following ethical permission and informed consent, DNA was extracted from whole blood samples in five patients with histologically proven African degenerative leiomyopathy. PCR amplification of ACTG2 alpha gene products by semi-automated bi-directional sequencing analysis. Results were analysed using FinchTV Sequence Alignment Software and predicting bioinformatic investigation by PolyPhen 2 software.

RESULTS
Five new patients with the ADL phenotypes were prospectively investigated for variation in the Actin G2 gamma gene (ACTG2). ACTG2 gene variation occurred in exon 5 (c.463 A>G K119R), in three (60%). In addition, intronic variation t > c-IVS3 was identified in three with the K119 mutation plus further g >  c -IVS12 and t > c + IVS16(2), suggesting a possible haplotype. Bioinformatic modelling showed that these ACTG2 gene variations are highly non-conservative altering protein expression.

CONCLUSIONS
Recurrent Actin G2 smooth muscle gene variation in African degenerative visceral leiomyopathy is associated with abnormal muscle actin development.

Maluleke|T|T|
Mangray|H|H|
Arnold|M|M|
Moore|H A|HA|
Moore|S W|SW|

Visceral myopathy
African degenerative leiomyopathy
Children
ADL


Effect of extraction solvents and plant parts used on the antihyperlipidemic and antioxidant effects of Garcinia atroviridis: a comparative study.

Abstract:
BACKGROUND
Garcinia atroviridis is a seasonal fruit plant found in many parts of South East Asia. The fruit rind is used in cooking and traditionally consumed for various reasons, including to lower blood cholesterol. A comparative study was undertaken to investigate the influence of extraction solvents and plant parts used on the lipid-lowering and antioxidant activities of Garcinia atroviridis.

RESULTS
Aqueous extracts showed better antihyperlipidemic activity than the methanol extracts. Aqueous extract of ripe fruit showed the most potent antihyperlipidemic activity, comparable to that of atorvastatin. It significantly reduced the total cholesterol (P < 0.05), triglycerides (P < 0.01), low-density lipoprotein (P < 0.01), very-low-density lipoprotein (P < 0.01) and atherogenic index (P < 0.01). In contrast, antioxidant activities of methanol extracts of all parts of G. atroviridis were higher than their respective aqueous extracts, whereby the stem and leaves extracts showed better antioxidant activities than the fruits.

CONCLUSION
Aqueous and methanol extracts of G. atroviridis showed higher antihyperlipidemic and antioxidant effects, respectively. Total phenolic and flavonoid contents showed significant correlations with antioxidant but not with antihyperlipidemic activities, indicating the involvement of other compounds. Contrary to the traditional belief, the present findings suggest that the fruit has higher antihyperlipidemic potential than the fruit rind.

Al-Mansoub|Majed Ahmed|MA|
Asmawi|Mohd Zaini|MZ|
Murugaiyah|Vikneswaran|V|

antihyperlipidemic
antioxidant
Garcinia atroviridis
total cholesterol
triglycerides
atherogenic index


Ionic strength of electrospray droplets affects charging of DNA oligonucleotides.

Abstract: The fundamental aspects of charging in electrospray ionization (ESI) are hotly debated. In the present study, ESI charging of DNA oligonucleotides was explored in both positive (ESI+) and negative (ESI-) polarity using mass spectrometry detection. Single-stranded 12-mer CCCCAATTCCCC in buffer solution (aqueous NH4Ac, 100 mM) produced similar charge state distribution (CSD) in either ESI+ or ESI-. Similarity of CSD in ESI+ and ESI- was also observed for the double-stranded 12-mer CGCGAATTCGCG. By adding typical low-vapor reagents (e.g. m-nitro benzyl alcohol, m-NBA; sulfolane) into the same buffer solution (<0.5% w/v), both CCCCAATTCCCC and CGCGAATTCGCG revealed strong supercharging (SC) effect in ESI-, while very little or no SC effect was observed in ESI+. With either sulfolane or m-NBA, the CGCGAATTCGCG duplex dissociated into single strands in ESI-. No SC was observed in both ESI+ and ESI- for thermally denatured CGCGAATTCGCG duplex in NH4 Ac buffer without the reagents. These findings are difficult to reconcile with the earlier model, which attributes SC in aqueous buffer solution to the conformational changes of analytes. Our observations suggest that the ionic strength of ESI droplets strongly affects the CSD of biopolymers such as DNA oligonucleotides and that SC effect is related to the depletion of ionic strength during the ESI process.

DNA oligonucleotides
charge state distribution
supercharging
ESI mechanisms
gas-phase ions


Genotypic characterization of multi-drug-resistant Mycobacterium tuberculosis isolates in Myanmar.

Abstract: The number of multi-drug-resistant tuberculosis (MDR-TB) cases is rising worldwide. As a countermeasure against this situation, the implementation of rapid molecular tests to identify MDR-TB would be effective. To develop such tests, information on the frequency and distribution of mutations associating with phenotypic drug resistance in Mycobacterium tuberculosis is required in each country. During 2010, the common mutations in the rpoB, katG and inhA of 178 phenotypically MDR M. tuberculosis isolates collected by the National Tuberculosis Control Program (NTP) in Myanmar were investigated by DNA sequencing. Mutations affecting the 81-bp rifampicin (RIF) resistance-determining region (RRDR) of the rpoB were identified in 127 of 178 isolates (71.3%). Two of the most frequently affected codons were 531 and 526, with percentages of 48.3% and 14.0% respectively. For isoniazid (INH) resistance, 114 of 178 MDR-TB isolates (64.0%) had mutations in the katG in which a mutation-conferring amino acid substitution at codon 315 from Ser to Thr was the most common. Mutations in the inhA regulatory region were also detected in 20 (11.2%) isolates, with the majority at position -15. Distinct mutation rate and pattern from surrounding countries might suggest that MDR-TB has developed and spread domestically in Myanmar.

Aye|Khin Saw|KS|
Nakajima|Chie|C|
Yamaguchi|Tomoyuki|T|
Win|Min Min|MM|
Shwe|Mu Mu|MM|
Win|Aye Aye|AA|
Lwin|Thandar|T|
Nyunt|Wint Wint|WW|
Ti|Ti|T|
Suzuki|Yasuhiko|Y|

D024901:Drug Resistance, Multiple, Bacterial

Mycobacterium tuberculosis
Myanmar
Resistance
Rifampicin
Isoniazid


Ecosystem Microbiology of Coral Reefs: Linking Genomic, Metabolomic, and Biogeochemical Dynamics from Animal Symbioses to Reefscape Processes.

Abstract: Over the past 2 decades, molecular techniques have established the critical role of both free-living and host-associated microbial partnerships in the environment. Advancing research to link microbial community dynamics simultaneously to host physiology and ecosystem biogeochemistry is required to broaden our understanding of the ecological roles of environmental microbes. Studies on coral reefs are actively integrating these data streams at multiple levels, from the symbiotic habitat of the coral holobiont to microbially mediated interactions between corals and algae to the effects of these interactions on the microbial community structure, metabolism, and organic geochemistry of the reef ecosystem. Coral reefs endure multiple anthropogenic impacts, including pollution, overfishing, and global change. In this context, we must develop ecosystem microbiology with an eye to providing managers with microbial indicators of reef ecosystem processes, coral health, and resilience to both local and global stressors.

ecosystem
coral reef
metabolomics
biogeochemistry
metagenomics


Method for RNA extraction and transcriptomic analysis of single fungal spores.

Abstract: Transcriptomic analysis of single cells has been increasingly in demand in recent years, thanks to technological and methodological advances as well as growing recognition of the importance of individuals in biological systems. However, the majority of these studies have been performed in mammalian cells, due to their ease of lysis and high RNA content. No single cell transcriptomic analysis has yet been described in microbial spores, even though it is known that heterogeneity at the phenotype level exists among individual spores. Transcriptomic analysis of single spores is challenging, in part due to the physically robust nature of the spore wall. This precludes the use of methods commonly used for mammalian cells. Here, we describe a simple method for extraction and amplification of transcripts from single fungal conidia (asexual spores), and its application in single-cell transcriptomics studies. The method can also be used for studies of small numbers of fungal conidia, which may be necessary in the case of limited sample availability, low-abundance transcripts or interest in small subpopulations of conidia. •The method allows detection of transcripts from single conidia of Aspergillus niger•The method allows detection of genomic DNA from single conidia of Aspergillus niger.

Geoghegan|Ivey A|IA|
Emes|Richard D|RD|
Archer|David B|DB|
Avery|Simon V|SV|

RNA extraction
Spores
Conidia
Single-cell transcriptomics
Aspergillus niger
Phenotypic heterogeneity


Distinct Effectiveness of Oritavancin against Tolerance-Induced Staphylococcus aureus.

Abstract: Within a sufficiently large bacterial population, some members will naturally adopt an alternate, metabolically-active state that favors small molecule synthesis over cell division. These isogenic "tolerant" subpopulations have variable responses during antibiotic exposure and can remain viable in the presence of typically bactericidal concentrations. In this study, we determine the ability of typical and atypical antistaphylococcal therapies to reduce the viability of mupirocin-induced tolerant Staphylococcus aureus bacteria. Overall, tolerance-induced staphylococci exhibited a markedly decreased rate and extent of killing following antibiotic exposure. However, oritavancin remained effective at maintaining a similar extent of killing. Further studies to investigate the role of oritavancin against recurrent or relapse staphylococcal infection are warranted.

oritavancin tolerance MRSA lipoglycopeptide persistence


Pseudomonas aeruginosa mannose-sensitive hemagglutinin inhibits proliferation and invasion via the PTEN/AKT pathway in HeLa cells.

Abstract: We investigated the effects of Pseudomonas aeruginosa mannose-sensitive hemagglutinin (PA-MSHA) on the proliferation and invasion of human cervical cancer cell lines, as well as the molecular pathways underlying these effects. MTT cell proliferation assays revealed a time- and concentration-dependent cytotoxic effect of PA-MSHA on HeLa cells but not H8 cells. Flow cytometry with propidium iodide and annexin-V-fluorescein isothiocyanate labeling (FITC) indicated that various concentrations of PA-MSHA could induce apoptosis and G2-M cell cycle arrest in HeLa cells. PA-MSHA also impaired the migration and invasion abilities of HeLa cells in Wound healing and Transwell invasion assays. Western blot results demonstrated that PA-MSHA reduced the expression of p-AKT, p-GSK3β, BCL-2, Vimentin and β-catenin, but increased the levels of PTEN, BAD, BAX and E-cadherin in HeLa cells. Importantly, PTEN siRNA induced the activity of p-AKT, while PA-MSHA partly inhibited this induction, indicating that PA-MSHA may reduce the cell proliferation and invasion potential by activating PTEN and thus inhibiting the AKT pathway in vitro. These data suggest the potential application of PA-MSHA to the treatment of human cervical cancer.

Yin|Tie-Qiu|TQ| Ou-Yang|Xuan|X| Jiao|Fang-Yan|FY| Huang|Lu-Ping|LP| Tang|Xu-Dong|XD| Ren|Bi-Qiong|BQ|

D000071679:Glycogen Synthase Kinase 3 beta

PTEN
PA-MSHA
cervical cancer
p-AKT
p-GSK3β


A biogeochemical approach to evaluate the optimization and effectiveness of hypolimnetic withdrawal.

Abstract: Hypolimnetic withdrawal (HW) is a lake restoration method that is based on the removal of phosphorus (P) along with near-bottom water. While it has often proven to be effective, the method also sets challenges: it is about balancing between effective P removal and maintenance of the thermal stratification of the lake. The success of different HW projects has been reviewed in some studies retrospectively, but scientific literature still lacks studies that use detailed data on the lake biogeochemistry to scale and optimize the method in advance, and to predict the outcomes of the restoration measure. In the current study, we investigated the seasonal biogeochemistry, P stocks and thermal stratification of a eutrophic lake (Lake Kymijärvi/Myllypohja basin, southern Finland) to determine an optimal withdrawal rate, to assess its effects on stratification, and to evaluate the expected success of HW. We found that by adjusting HW with P diffusive fluxes from the sediment (diffusion-adjusted HW), it is possible to remove a notable part of the cycling P without causing major disturbances to the thermal stratification even in a relatively shallow lake. Our results show that HW can have great potential in lake restoration: diffusion-adjusted HW in our study lake could increase the annual P output by 35-46%, shifting the P budget of the lake to negative. We thus propose a novel approach to optimize HW on the basis of the diffusive flux of P from the sediment, with the goal of extracting P continuously at an equivalent rate to the diffusive flux. We finally discuss how this can be achieved more effectively with HW based on a closed-circuit system.

Silvonen|Soila|S| Niemistö|Juha|J| Csibrán|Adrián|A| Jilbert|Tom|T| Torma|Péter|P| Krámer|Tamás|T| Nurminen|Leena|L| Horppila|Jukka|J|

Lake restoration
Phosphorus
Thermal stratification
Eutrophication
Sediment
Internal loading


Heterogeneity in long term health outcomes of migrants within Italy.

Abstract: This article examines the long term physical and mental health effects of internal migration focusing on a relatively unique migration experience concentrated over a short period between 1950 and 1970 from the South to the North of Italy. We find a positive and statistically significant association between migration, its timing and physical health for migrant females, which we show are likely to represent rural females in both the early and the late cohort. We find less defined evidence of migration-health association for mental health. We link our findings to the economic transition and labor market transformation that Italy witnessed in that era. Male migrants were likely to be positively selected to migration, but harsh working conditions were likely to downplay this differential. On the contrary, women migrants, by and large, would not engage in the formal labor market avoiding the ill effects of working environments, at the same time benefiting from better living conditions and health care in the destination regions.

Italy
Finite mixture models
Mental health status
Migration decisions
Physical health status


Experimental Evaluation of the Effects of Low-Dose Heparin on the Behavior and Morphofunctional Status of the Liver in Wistar Rats with Posttraumatic Stress Disorders.

Abstract: Posttraumatic stress disorders were induced in Wistar rats by modeling predatory stress. Animals tested in elevated plus-maze demonstrated signs of high anxiety and difficulties in space orientation. Behavioral disorders were paralleled by degenerative changes in hepatocytes. A course of low-dose high-molecular heparin after stress exposure promoted effective adaptation and normalization of behavioral and morphofunctional disorders. Analysis of the results indicated good prospects of heparin as an effective drug under conditions of exposure to extreme factors of psychotraumatic type.

liver
posttraumatic stress disorders
elevated plus-maze
psychoemotional manifestations


A Hierarchical Model for Accuracy and Choice on Standardized Tests.

Abstract: This paper assesses the psychometric value of allowing test-takers choice in standardized testing. New theoretical results examine the conditions where allowing choice improves score precision. A hierarchical framework is presented for jointly modeling the accuracy of cognitive responses and item choices. The statistical methodology is disseminated in the 'cIRT' R package. An 'answer two, choose one' (A2C1) test administration design is introduced to avoid challenges associated with nonignorable missing data. Experimental results suggest that the A2C1 design and payout structure encouraged subjects to choose items consistent with their cognitive trait levels. Substantively, the experimental data suggest that item choices yielded comparable information and discrimination ability as cognitive items. Given there are no clear guidelines for writing more or less discriminating items, one practical implication is that choice can serve as a mechanism to improve score precision.

Culpepper|Steven Andrew|SA|
Balamuta|James Joseph|JJ|

choice
Bayesian statistics
Thurstonian models
high-stakes testing
item response theory


Functional outcomes, morbidity, mortality, and fracture healing in 58 consecutive patients with geriatric odontoid fracture treated with cervical collar or posterior fusion.

Abstract: Controversy exists as to the most effective management option for elderly patients with type II odontoid fractures. The purpose of this study is to evaluate outcomes associated with rigid cervical collar and posterior fusion surgery. Patients with ≥ 50% odontoid displacement were treated with posterior fusion surgery including C1-2 (PSF group, n = 25, average age = 80 years). Patients with < 50% odontoid displacement were treated with a rigid cervical collar for 12 weeks (collar group, n = 33, average age = 83 years). These inhomogeneous groups were followed for an average of 14 months. Fracture healing rates were higher in the operative group (28% versus 6%). Neck Disability Index scores were slightly lower in the nonoperative group (13 versus 18.3, p = 0.23). Analogue pain scores were also slightly lower in the nonoperative group (1.3 versus 1.9, p = 0.26). The mortality rate was 12.5% in the collar group and 20% in the operative group. Complications were higher in the operative group (24% versus 6%). Rates of type II odontoid facture healing and stability appear to be higher in geriatric patients treated with posterior fusion surgery. Fracture healing and stability did not correlate with improved outcomes with respect to levels of pain, function, and satisfaction. Mortality and complication rates are lower in those patients with lesser-displaced fractures who are treated with a cervical collar and early mobilization.

Molinari|William J|WJ|
Molinari|Robert W|RW|
Khera|Oner A|OA|
Gruhn|William L|WL|

fracture geriatric odontoid management operative nonoperative


Tick-borne encephalitis - a review of current epidemiology, clinical symptoms, management and prevention.

Abstract: Tick-borne encephalitis virus (TBEV), which causes central nervous system infections, is a major health problem in Europe and Asia. This virus is transmitted mainly via the bite of a tick. However, an infection may also occur as a result of consuming raw milk. In 2018, a total of 3 092 cases of tick-borne encephalitis (TBE) were reported in EU countries. In recent years, TBE has emerged in previously unaffected regions; thus, new endemic areas have been identified. Most cases of TBE occur in spring and autumn, which correlates with increased tick activity. TBE is found in all age groups, including infants. The clinical presentation of TBE varies, but the severity of the infection and risk of complications increase with age. Post-encephalitic syndrome, which affects up to 50% of infected individuals, significantly reduces quality of life. Currently, there is no effective treatment for TBE, and supportive management is used in the acute phase of the disease. Therefore, anti-TBE immunization and the avoidance of tick bites are of key importance in preventing this infection.


Granulomatous Lung Disease: A Novel Complication following Metallosis from Hip Arthroplasty.

Abstract: A case of a female patient with local and systemic complications of metallosis, following catastrophic wear of a revised hip arthroplasty, is presented. The patient had a history of a fractured ceramic-on-ceramic implant, exchanged with a metal-on-polyethylene prosthesis. Systemic complications included sarcoidosis-like reactions, presenting as granulomatous lung disease, along with chorioretinitis, erythema nodosum, and cardiomyopathy. High local and circulating cobalt and chromium levels established the diagnosis. The patient underwent extensive debridement and implant revision. One year postoperatively, she had no respiratory symptoms or functional impairment. Local and systemic complications of metallosis after hip arthroplasty should be promptly recognized and treated operatively.

Ceramics
Heavy metal toxicity
Hip replacement arthroplasty
Pulmonary sarcoidosis
Reoperation


Discovery and dissection of metabolic oscillations in the microaerobic nitric oxide response network of Escherichia coli.

Abstract: The virulence of many pathogens depends upon their ability to cope with immune-generated nitric oxide (NO·). In Escherichia coli, the major NO· detoxification systems are Hmp, an NO· dioxygenase (NOD), and NorV, an NO· reductase (NOR). It is well established that Hmp is the dominant system under aerobic conditions, whereas NorV dominates anaerobic conditions; however, the quantitative contributions of these systems under the physiologically relevant microaerobic regime remain ill defined. Here, we investigated NO· detoxification in environments ranging from 0 to 50 μM O2, and discovered a regime in which E. coli NO· defenses were severely compromised, as well as conditions that exhibited oscillations in the concentration of NO·. Using an integrated computational and experimental approach, E. coli NO· detoxification was found to be extremely impaired at low O2 due to a combination of its inhibitory effects on NorV, Hmp, and translational activities, whereas oscillations were found to result from a kinetic competition for O2 between Hmp and respiratory cytochromes. Because at least 777 different bacterial species contain the genetic requirements of this stress response oscillator, we hypothesize that such oscillatory behavior could be a widespread phenomenon. In support of this hypothesis,Pseudomonas aeruginosa, whose respiratory and NO· response networks differ considerably from those of E. coli, was found to exhibit analogous oscillations in low O2 environments. This work provides insight into how bacterial NO· defenses function under the low O2 conditions that are likely to be encountered within host environments.

Robinson|Jonathan L|JL|
Brynildsen|Mark P|MP|

D000332:Aerobiosis
D003198:Computer Simulation
D004093:Dihydropteridine Reductase
D004926:Escherichia coli
D029968:Escherichia coli Proteins
D006420:Hemeproteins
D054884:Host-Pathogen Interactions
D008954:Models, Biological
D009247:NADH, NADPH Oxidoreductases
D009569:Nitric Oxide
D010088:Oxidoreductases
D010100:Oxygen
D011550:Pseudomonas aeruginosa
D013045:Species Specificity

microaerobic
E. coli
Pseudomonas aeruginosa
kinetic modeling
nitrosative stress


Targeting strategies for drug delivery to the kidney: From renal glomeruli to tubules.

Abstract: Kidney diseases have become a global public health problem. The application of kidney-targeted drug-delivery systems in the management of kidney diseases has profound transformative potential. Kidney-targeted drug delivery can reduce the undesired side effects of often potent drugs and enhance drug efficacy in alleviating the kidney disease. Here, we review the literature on the potential strategies for targeting drugs to the kidneys. Specifically, we provide a broad overview of the targeting vectors and targeting pathways for renal tubules and glomeruli, as well as how the unique structural features of the glomerulus and the receptor-mediated internalization pathways of the tubules allows for drug targeting. Finally, we summarized the literature examples of drug delivery to the kidneys and elaborated strategies suitable for renal targeting to provide new therapeutic approaches for kidney diseases.

Liu|Chun-Ping|CP|0000-0003-1046-3386
Hu|You|Y|
Lin|Ju-Chun|JC|
Fu|Hua-Lin|HL|
Lim|Lee Yong|LY|
Yuan|Zhi-Xiang|ZX|0000-0001-7809-2580

kidney
renal tubules
drug targeting
mesangial cells
podocytes


Carpal Tunnel Syndrome: Effectiveness of Physical Therapy and Electrophysical Modalities. An Updated Systematic Review of Randomized Controlled Trials.

Abstract:
OBJECTIVE
To review scientific literature studying the effectiveness of physical therapy and electrophysical modalities for carpal tunnel syndrome (CTS).

DATA SOURCES
The Cochrane Library, PubMed, Embase, CINAHL, and Physiotherapy Evidence Database.

STUDY SELECTION
Two reviewers independently applied the inclusion criteria to select potential eligible studies.

DATA EXTRACTION
Two reviewers independently extracted the data and assessed the methodologic quality using the Cochrane Risk of Bias Tool.

DATA SYNTHESIS
A best-evidence synthesis was performed to summarize the results of the included studies (2 reviews and 22 randomized controlled trials [RCTs]). For physical therapy, moderate evidence was found for myofascial massage therapy versus ischemic compression on latent, or active, trigger points or low-level laser therapy in the short term. For several electrophysical modalities, moderate evidence was found in the short term (ultrasound vs placebo, ultrasound as single intervention vs other nonsurgical interventions, ultrasound vs corticosteroid injection plus a neutral wrist splint, local microwave hyperthermia vs placebo, iontophoresis vs phonophoresis, pulsed radiofrequency added to wrist splint, continuous vs pulsed vs placebo shortwave diathermy, and interferential current vs transcutaneous electrical nerve stimulation vs a night-only wrist splint). In the midterm, moderate evidence was found in favor of radial extracorporeal shockwave therapy (ESWT) added to a neutral wrist splint, in favor of ESWT versus ultrasound, or cryo-ultrasound, and in favor of ultrasound versus placebo. For all other interventions studied, only limited, conflicting, or no evidence was found. No RCTs investigating the long-term effects of physical therapy and electrophysical modalities were found. Because of heterogeneity in the treatment parameters used in the included RCTs, optimal treatment parameters could not be identified.

CONCLUSIONS
Moderate evidence was found for several physical therapy and electrophysical modalities for CTS in the short term and midterm. Future studies should concentrate on long-term effects and which treatment parameters of physical therapy and electrophysical modalities are most effective for CTS.

Huisstede|Bionka M|BM|
Hoogvliet|Peter|P|
Franke|Thierry P|TP|
Randsdorp|Manon S|MS|
Koes|Bart W|BW|

D016032:Randomized Controlled Trials as Topic

Carpal tunnel syndrome
Physical therapy modalities
Rehabilitation
Review [publication type]
Treatment outcome


The Role of Intestinal Permeability in Gastrointestinal Disorders and Current Methods of Evaluation.

Abstract: An increased intestinal permeability has been described in various gastrointestinal and non-gastrointestinal disorders. Nevertheless, the concept and definition of intestinal permeability is relatively broad and includes not only an altered paracellular route, regulated by tight junction proteins, but also the transcellular route involving membrane transporters and channels, and endocytic mechanisms. Paracellular intestinal permeability can be assessed in vivo by using different molecules (e.g., sugars, polyethylene glycols, 51Cr-EDTA) and ex vivo in Ussing chambers combining electrophysiology and probes of different molecular sizes. The latter is still the gold standard technique for assessing the epithelial barrier function, whereas in vivo techniques, including putative blood biomarkers such as intestinal fatty acid-binding protein and zonulin, are broadly used despite limitations. In the second part of the review, the current evidence of the role of impaired barrier function in the pathophysiology of selected gastrointestinal and liver diseases is discussed. Celiac disease is one of the conditions with the best evidence for impaired barrier function playing a crucial role with zonulin as its proposed regulator. Increased permeability is clearly present in inflammatory bowel disease, but the question of whether this is a primary event or a consequence of inflammation remains unsolved. The gut-liver axis with a crucial role in impaired intestinal barrier function is increasingly recognized in chronic alcoholic and metabolic liver disease. Finally, the current evidence does not support an important role for increased permeability in bile acid diarrhea.

intestinal permeability
paracellular route
transcellular route
inflammatory bowel disease
GI diseases
bile acid malabsorption
chronic liver disease
coeliac disease


Research advances on the multiple uses of Moringa oleifera: A sustainable alternative for socially neglected population.

Abstract: Moringa oleifera Lam (Moringaceae) is a plant with high nutritional and medicinal value. Native to India, it is now widely distributed throughout tropical and subtropical regions of the world. Its different parts are sources of proteins, vitamins and minerals and present different pharmacological and biotechnological potential. Moreover, M. oleifera seeds are widely used in water and effluent treatment, for their coagulation, flocculation and sedimentation properties, their ability of improving water quality, by reducing organic matter and microbial load, with special applicability in intensive animal production systems, such as aquaculture. In addition, due to its high nutritional value and several medicinal properties, this tree may act as a nutritional and medical alternative for socially neglected populations. In this context, this review gathers information on M. oleifera, emphasizing its chemical constituents, nutritional, pharmacological and antimicrobial properties, applications in the treatment of water effluents, and ecological and social aspects.

Castelo-Branco|Débora de Souza Collares Maia|DSCM|

Moringa oleifera
Nutrition
Biotechnology
Aquaculture
Health


Identification of genes associated with asexual reproduction in Phyllosticta citricarpa mutants obtained through Agrobacterium tumefaciens transformation.

Abstract: Phyllosticta citricarpa is the epidemiological agent of Citrus Black Spot (CBS) disease, which is responsible for large economic losses worldwide. CBS is characterized by the presence of spores (pycnidiospores) in dark lesions of fruit, which are also responsible for short distance dispersal of the disease. The identification of genes involved in asexual reproduction of P. citricarpa can be an alternative for directional disease control. We analyzed a library of mutants obtained through Agrobacterium tumefaciens transformation system, looking for alterations in growth and reproductive structure formation. Two mutant strains were found to have lost the ability to form pycnidia. The flanking T-DNA insertion regions were identified on P. citricarpa genome by using blast analysis and further gene prediction. The predicted genes containing the T-DNA insertions were identified as Spindle Poison Sensitivity Scp3, Ion Transport protein, and Cullin Binding proteins. The Ion Transport and Cullin Binding proteins are known to be correlated with sexual and asexual reproduction in fungi; however, the exact mechanism by which these proteins act on spore formation in P. citricarpa needs to be better characterized. The Scp3 proteins are suggested here for the first time as being associated with asexual reproduction in fungus. This protein is associated with microtubule formation, and as microtubules play an essential role as spindle machinery for chromosome segregation and cytokinesis, insertions in this gene can lead to abnormal formations, such as that observed here in P. citricarpa. We suggest these genes as new targets for fungicide development and CBS disease control, by iRNA.

Goulin|Eduardo Henrique|EH|
Savi|Daiani Cristina|DC|
Petters|Desirrê Alexia Lourenço|DAL|
Kava|Vanessa|V|
Galli-Terasawa|Lygia|L|
Silva|Geraldo José|GJ|
Glienke|Chirlei|C|

D015966:Gene Expression Regulation, Fungal

Asexual reproduction
Phyllosticta citricarpa
Agrobacterium tumefaciens
Ion transport protein
Cullin binding protein
Spindle poison sensitivity Spc3


Malignant primary tumor in left atrium with mitral valve invasion, pulmonary veins and cerebral metastasis. A case report.

Abstract:
Introduction
The incidence of cardiac primary tumors is estimated to be 0.0017-0.28%, of which 25% are malignant, occupying mainly right cavities.

Clinical case
Patient who present with neurological symptoms due to brain metastasis of primary cardiac tumor in the left atrium, infiltrating the mitral valve and pulmonary veins. Tumor resection was performed with mitral valve replacement and atrial re-modeling with the use of the left appendage.

Conclusions
Imaging techniques are fundamental for the diagnosis of this pathology, since the majority of cardiac tumors are asymptomatic until late stages.

Reynoso-Hermosillo|Miguel|M|
Sandoval-García|Jaime|J|
López-Rosales|Baltazar|B|
Esparza-Villarruel|Antonio|A|
Díaz-Sifuentes|José Ma|JM|
García-Martínez|David|D|
Ángeles-Bueno|Wenceslao G|WG|

D019918:Heart Valve Prosthesis Implantation

Cardiac primary tumor
Brain metastasis
Metástasis cerebrales
Primary intimal sarcoma
Sarcoma intimal auricular
Surgical management
Tratamiento quirúrgico
Tumor primario cardiaco


Interviewing and Counseling the Dizzy Patient with Focus on Quality of Life.

Abstract: When interviewing a patient presenting with dizziness, it is imperative to both diagnosis and treatment for the clinician to identify the impact dizziness has on the patient's productivity, general function level and cognition. and cognition. Psychiatric comorbidities and concurrent sleep disturbances are common in this patient population and identification of these additional factors is important in implementing a holistic, multidisciplinary treatment plan and ultimately improves the patient's outcome.

Counseling
Dizziness
Psychiatric comorbidities
Sleep Disturbances
Multidisciplinary treatment
Cognitive function
Quality of life (QOL)
Vestibular disorders


Conceptualization, operationalization, and content validity of the EQOL-questionnaire measuring quality of life and participation for persons with disabilities.

Abstract:
BACKGROUND
Measurement of quality of life demands thoroughly developed and validated instruments. The development steps from theory to concepts and from empirical data to items are sparsely described in the literature of questionnaire development. Furthermore, there seems to be a need for an instrument measuring quality of life and participation in a population with diverse disabilities. The aim of this paper was to present and discuss the initial steps in the development of the Electronic Quality of Life questionnaire (EQOL).

METHODS
The development of EQOL included six steps: 1) Establishing conceptual understanding; 2) Development of interview guides which build on the conceptual understanding; 3) Qualitative interviews of 55 participants (10-40 years old) with different types and severities of disabilities; 4) Conceptualization of domains identified in the qualitative data through thematic analysis; 5) Operationalization of the identified domains into items and; 6) Evaluation of content validity of the first version of the EQOL-measure. Content validity was examined by cognitive interviews with participants in the target group as well as by continuous feedback from an advisory board.

RESULTS
We identified six domains (function and health, environment (physical and social), social network, wellbeing, occupation, and managing strategies) based on themes derived from the qualitative interviews and on conceptual discussions within the author group. These domains were incorporated in a conceptual model and items were generated to measure the content of each domain. Participants expressed satisfaction with EQOL but most participants felt that there were too many items.

CONCLUSIONS
In total, 191 items were included in the questionnaire. Participants felt that the EQOL-questionnaire was relevant to their quality of life and participation. We have shown that it is possible to include quality of life and participation for people with various disabilities in one instrument. Although capturing less detail than a condition specific instrument, EQOL includes aspects perceived important for people with disabilities who are not included in general surveys. This is relevant when for example evaluating environmental adaptations and when comparing populations with various disabilities.

Jespersen|Louise Norman|LN|
Michelsen|Susan Ishøy|SI|
Holstein|Bjørn Evald|BE|
Tjørnhøj-Thomsen|Tine|T|
Due|Pernille|P|

Conceptualization
Operationalization
Content validity
Measurement
Quality of life
Participation
Disability
Instrument
Questionnaire


Integrating science and practice in pharmacy curricula.

Abstract: An integrated curriculum is one where the summation of different academic disciplines forms a coherent whole and, importantly, where the relationships between the different disciplines have been carefully and strategically considered when forming the composite. Within pharmacy curriculum integration is important in order to produce graduates who have the capacity to apply their knowledge to a range of complex problems where available information is often incomplete. This paper discusses the development of an integrated curriculum in which students are presented with an organized, logical sequence of material, but still challenged to make their own integrations and develop as integrative thinkers. An evidence-based model upon which an interdisciplinary undergraduate pharmacy curriculum can be built is presented.

Husband|Andrew K|AK|
Todd|Adam|A|
Fulton|John|J|

integrated curriculum
curriculum
assessment
pharmacy education


Improving the management effectiveness and decision-making by stakeholders' perspectives: A case study in a protected area from the Brazilian Atlantic Forest.

Abstract: Assessing management effectiveness in protected areas is a fundamental instrument to achieve socio-biodiversity protection goals. This study aimed to analyze the management effectiveness of Cunhambebe State Park (from now on, "PEC") in the State of Rio de Janeiro in Brazil, from the perception of stakeholders and the multi-temporal analysis of land use and land cover between 1998 and 2018. We used the Rapid Assessment and Prioritization of Protected Area Management method for a participatory approach. Seventy-two indicators were used and applied to assess the perception of stakeholders related to the Advisory Council. The management effectiveness of PEC was classified as moderately satisfactory (63.41%). Indicators of "Legal security", "Vulnerability", "Site design and planning" and "Financial resources" revealed the weaknesses and threats of management and what should be the priority projects for better effectiveness. Through the multi-temporal analysis, we identified that the advances of pasture and urban areas are the highest pressures and threats, as perceived by stakeholders. In our case study, we provide evidence of actions that must be performed by the PEC management team. These actions must consider the weaknesses and threats presented by the SWOT analysis. Finally, we recommend some political and management measures: 1) Financial resources for the land regularization of areas overlapping with PEC, 2) Guidelines about PEC areas must be included in the Master Plans of municipalities that cover PEC limits, 3) Technical assistance to improve land management, and 4) Strengthen environmental education initiatives at all school levels.

D003247:Conservation of Natural Resources

Atlantic forest
Land use and land cover
Protected area management
Conservation planning
RAPPAM


Variations in Sugar Content of Flavored Milks and Yogurts: A Cross-Sectional Study across 3 Countries.

Abstract:
Background
The consumption of dairy products is encouraged at all life stages as a nutrient-rich component of the diet. However, many milk and yogurt products, particularly flavored varieties, may contain large amounts of free sugar.

Objectives
The aim of this paper was to evaluate the availability and sugar content of flavored milks and yogurts in supermarkets across 3 countries: Australia, England, and South.

Methods
Nutrition information for flavored milks and yogurts was collected by trained researchers and supplemented by crowd-sourced data from a smartphone application. Data were extracted in April 2018 and 3724 milk and yogurt products were available for analysis. Mean sugar concentrations were compared across countries with the use of ANOVA followed by Tukey's post-hoc pairwise comparisons. Sugar concentrations were compared with the UK's "green" traffic-light classifications.

Results
Approximately 74% (n = 2753) of all products were flavored. Flavored products contained nearly twice the average total sugar content of unflavored products, with substantial variability: mean total sugar was 9.1 g/100 mL (range: 4.3-15.0 g/100 mL) and 11.5 g/100 g (range: 0.1-22.6 g/100 g) for flavored milks and yogurts, respectively. Free sugars contributed an estimated 41% and 42% of total sugar in milks and yogurts, respectively. Flavored milks in England had ∼0.7 g/100 mL higher total sugar on average compared with Australia and South Africa (P ≤ 0.04), whereas flavored yogurts in South Africa had the lowest average total sugar (∼2 g/100 g lower than England and Australia; P < 0.001). Less than 4% of flavored products would receive a "green" rating under the UK traffic-light labeling scheme.

Conclusions
In Australia, England, and South Africa, flavored milks and yogurts are highly prevalent in the food supply and contain significantly higher concentrations of total and added sugars than unflavored products.

sugar
milk
yogurt
dairy
free sugar
noncommunicable disease
nutrition label
public health
sugar reduction


Neuronal Correlates of Small Animal Phobia in Human Subjects through fMRI: The Role of the Number and Proximity of Stimuli.

Abstract: Brain regions involved in small-animal phobia include subcortical and cortical areas. The present study explored the neuronal correlates of small-animal phobia through fMRI data to determine whether a manipulation of number and proximity parameters affects the neurobiology of the processing of feared stimuli. The participants were 40 individuals with phobia and 40 individuals without phobia (28.7% male and 71.3% female). They watched videos of real and virtual images of spiders, cockroaches and lizards in motion presented more or less nearby with one or three stimuli in the different conditions. The results suggested a differential brain activity between participants with and without phobia depending on the proximity and number of phobic stimuli. Proximity activated the motor response marked by the precentral gyrus and the cingulate gyrus. By contrast, the number of stimuli was associated with significant sensory activity in the postcentral gyrus and ventromedial prefrontal cortex. We also observed a greater activity in the occipital cortex when exploring the number compared to the proximity factor. Threatening stimuli presented nearby and those presented in greater numbers generated an intense phobic response, suggesting a different emotion regulation strategy. Based on these findings, exposure therapies might consider including proximity to the threat and number of stimuli as key factors in treatment.

fMRI
number
proximity
small-animal phobia
video images
virtual reality


VEGF delivery by smart polymeric PNIPAM nanoparticles affects both osteogenic and angiogenic capacities of human bone marrow stem cells.

Abstract:
OBJECTIVE
Bone tissue engineering (BTE) faces a major challenge with cell viability after implantation of a construct due to lack of functional vasculature within the implant. Human bone marrow derived mesenchymal stem cells (hBMSCs) have the potential to undergo transdifferentiation towards an endothelial cell phenotype, which may be appropriate for BTE in conjunction with the appropriate scaffolds and microenvironment.

HYPOTHESIS AND METHODS
We hypothesized that slow delivery of vascular endothelial growth factor (VEGF) by using nanoparticles in combination with osteogenic stimuli might enhance both osteogenic and angiogenic differentiation of angiogenic primed hBMSCs cultured in an osteogenic microenvironment. Therefore, we developed a new strategy to enhance vascularization in BTE in vitro by synthesis of smart temperature sensitive poly(N‑isopropylacrylamide) (PNIPAM) nanoparticles. We used PNIPAM nanoparticles loaded with collagen to investigate their ability to deliver VEGF for both angiogenic and osteogenic differentiation.

RESULTS
We used the free radical polymerization technique to synthesize PNIPAM nanoparticles, which had particle sizes of approximately 100 nm at 37 °C and LCST of 30-32 °C. The cumulative VEGF release after 72 h for VEGF loaded PNIPAM (VEGF-PNIPAM) nanoparticles was 70%; for VEGF-PNIPAM loaded collagen hydrogels, it was 23%, which indicated slower release of VEGF in the VEGF-PNIPAM loaded collagen system. Immunocytochemistry (ICC) and inverted microscope visualization confirmed endothelial differentiation and capillary-like tube formation in the osteogenic culture medium after 14 days. Quantitative real-time polymerase chain reaction (QRT-PCR) also confirmed expressions of collagen type I (Col I), runt-related transcription factor 2 (RUNX2), and osteocalcin (OCN) osteogenic markers along with expressions of platelet-endothelial cell adhesion molecule-1 (CD31), von Willebrand factor (vWF), and kinase insert domain receptor (KDR) angiogenic markers. Our data clearly showed that VEGF released from PNIPAM nanoparticles and VEGF-PNIPAM loaded collagen hydrogel could significantly contribute to the quality of engineered bone tissue.

Adibfar|Afsaneh|A|
Amoabediny|Ghassem|G|
Baghaban Eslaminejad|Mohamadreza|M|
Mohamadi|Javad|J|
Bagheri|Fatemeh|F|
Zandieh Doulabi|Behrouz|B|

D042461:Vascular Endothelial Growth Factor A


Fabrication and characterization of nuclear localization signal-conjugated glycol chitosan micelles for improving the nuclear delivery of doxorubicin.

Abstract:
BACKGROUND
Supramolecular micelles as drug-delivery vehicles are generally unable to enter the nucleus of nondividing cells. In the work reported here, nuclear localization signal (NLS)-modified polymeric micelles were studied with the aim of improving nuclear drug delivery.

METHODS
In this research, cholesterol-modified glycol chitosan (CHGC) was synthesized. NLS-conjugated CHGC (NCHGC) was synthesized and characterized using proton nuclear magnetic resonance spectroscopy, dynamic light scattering, and fluorescence spectroscopy. Doxorubicin (DOX), an anticancer drug with an intracellular site of action in the nucleus, was chosen as a model drug. DOX-loaded micelles were prepared by an emulsion/solvent evaporation method. The cellular uptake of different DOX formulations was analyzed by flow cytometry and confocal laser scanning microscopy. The cytotoxicity of blank micelles, free DOX, and DOX-loaded micelles in vitro was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in HeLa and HepG2 cells.

RESULTS
The degree of substitution was 5.9 cholesterol and 3.8 NLS groups per 100 sugar residues of the NCHGC conjugate. The critical aggregation concentration of the NCHGC micelles in aqueous solution was 0.0209 mg/mL. The DOX-loaded NCHGC (DNCHGC) micelles were observed as being almost spherical in shape under transmission electron microscopy, and the size was determined as 248 nm by dynamic light scattering. The DOX-loading content of the DNCHGC micelles was 10.1%. The DOX-loaded micelles showed slow drug-release behavior within 72 hours in vitro. The DNCHGC micelles exhibited greater cellular uptake and higher amounts of DOX in the nuclei of HeLa cells than free DOX and DOX-loaded CHGC (DCHGC) micelles. The half maximal inhibitory concentration (IC(50)) values of free DOX, DCHGC, and DNCHGC micelles against HepG2 cells were 4.063, 0.591, and 0.171 μg/mL, respectively. Moreover, the IC(50) values of free DOX (3.210 μg/mL) and the DCHGC micelles (1.413 μg/mL) against HeLa cells were nearly 6.96- and 3.07-fold (P < 0.01), respectively, higher than the IC(50) value of the DNCHGC micelles (0.461 μg/mL).

CONCLUSION
The results of this study suggest that novel NCHGC micelles could be a potential carrier for nucleus-targeting delivery.

Yu|Jingmou|J| Xie|Xin|X| Zheng|Meirong|M| Yu|Ling|L| Zhang|Lei|L| Zhao|Jianguo|J| Jiang|Dengzhao|D| Che|Xiangxin|X|

polymeric micelles
drug delivery
nucleus-targeting delivery


Ursolic acid and carvacrol may be potential inhibitors of dormancy protein small heat shock protein16.3 of Mycobacterium tuberculosis.

Abstract: Small heat shock protein16.3 (sHSP16.3) is a crucial protein for survival of Mycobacterium tuberculosis (MTB) in its host. Besides, this protein acts as a molecular chaperone during stress and is indispensable for MTB's growth, virulence and cell-wall thickening. sHSP16.3 is also a promising candidate for vaccine, serodiagnosis and drug design as well. In the present study, we have targeted sHSP16.3 with two phytochemicals, namely ursolic acid and carvacrol using in silico approach. Molecular docking analysis showed that both phytochemicals (ursolic acid and carvacrol) have docked with sHSP16.3 and shown tendency to inhibit the function of this vital protein of MTB. In addition, both compounds have exhibited strong compatibility with sHSP16.3 during whole 60 ns duration of molecular dynamics simulation. Further, the molecular mechanic/generalized Born/Poisson-Boltzmann surface area (MM/G/P/BSA) free energies were calculated which showed that both phytocompounds have stable and favourable binding energies causing strong binding with binding site of sHSP16.3. Taking together, the data of present study suggest that both phytocompounds may be potential inhibitor of sHSP16.3 of MTB and a best alternative to standard anti-tuberculosis drugs.

Jee|Babban|B| Kumar|Sanjay|S| Yadav|Renu|R| Singh|Yogesh|Y| Kumar|Anuj|A| Sharma|Naveen|N|

ursolic acid
carvacrol
Mycobacterium tuberculosis
sHSP16.3
in silico approach
MD: Molecular dynamics
MTB: Mycobacterium tuberculosis
RMSD: Root-mean-square deviation
TB: Tuberculosis
sHSP16.3: Small heat shock protein16.3


Basic fibroblast growth factor enhances cell proliferation in the dentate gyrus of neonatal rats following hypoxic-ischemic brain damage.

Abstract:
BACKGROUND
Perinatal hypoxic-ischemic insult is considered a major contributor to child mortality and morbidity and leads to neurological deficits in newborn infants. There has been a lack of promising neurotherapeutic interventions for hypoxic-ischemic brain damage (HIBD) for clinical application in infants. The present study aimed to investigate the correlation between neurogenesis and basic fibroblast growth factor (bFGF) in the hippocampal dentate gyrus (DG) region in neonatal rats following HIBD.

MATERIAL AND METHODS
Cell proliferation was examined by detecting BrdU signals, and the role of bFGF in cell proliferation in the DG region following neonatal HIBD was investigated.

RESULTS
Cell proliferation was induced by HIBD in the hippocampal DG of neonatal rats. Furthermore, bFGF gene expression was upregulated in the hippocampus in neonatal rats, particularly between 7 and 14 days after HIBD. Moreover, intraperitoneal injection of exogenous bFGF enhanced cell proliferation in the hippocampal DG following neonatal HIBD.

CONCLUSIONS
Taken together, these data indicate that cell proliferation in the DG could be induced by neonatal HIBD, and bFGF promotes proliferation following neonatal HIBD.

Zhu|Huan|H| Qiao|Lixing|L| Sun|Yao|Y| Yin|Liping|L| Huang|Li|L| Jiang|Li|L| Li|Jiaqing|J|

Cell proliferation
Dentate gyrus
bFGF
Neonatal HIBD
Cerebral hypoxia
Cerebral ischemia


Autophagic Turnover of Chloroplasts: Its Roles and Regulatory Mechanisms in Response to Sugar Starvation.

Abstract: Photosynthetic reactions in chloroplasts convert atmospheric carbon dioxide into starch and soluble sugars during the day. Starch, a transient storage form of sugar, is broken down into sugars as a source for respiratory energy production at night. Chloroplasts thus serve as the main sites of sugar production for photoautotrophic plant growth. Autophagy is an evolutionarily conserved intracellular process in eukaryotes that degrades organelles and proteins. Numerous studies have shown that autophagy is actively induced in sugar-starved plants. When photosynthetic sugar production is inhibited by environmental cues, chloroplasts themselves may become an attractive alternative energy source to sugars via their degradation. Here, we summarize the process of autophagic turnover of chloroplasts and its roles in plants in response to sugar starvation. We hypothesize that piecemeal-type chloroplast autophagy is specifically activated in plants in response to sugar starvation.

chloroplast
sugar starvation
autophagy
Rubisco-containing body
amino acid recycle
catabolism


The cost-effectiveness of dulaglutide versus insulin glargine for the treatment of type 2 diabetes mellitus in Japan.

Abstract:
AIMS
Dulaglutide is a new once weekly glucagon-like peptide-1 (GLP-1) receptor agonist administered via a disposable auto-injection pen for the management of type 2 diabetes mellitus (T2DM). The objective of this study was to estimate the cost-effectiveness of dulaglutide vs insulin glargine for the management of T2DM from a Japanese healthcare perspective, in accordance with recently approved Japanese Cost-Effectiveness Guidelines.

METHODS
The IQVIA CORE Diabetes Model (version 9) was used to estimate the long-term costs and effects of treatment with dulaglutide and insulin glargine. Direct comparative data from the Araki 2015 trial (NCT01584232) was used to inform the analysis. Costs associated with treatment and complications were derived from Japanese sources wherever possible and inflated to 2015 Japanese Yen (JPY). Utilities were based upon a European systematic review of diabetes utilities and adjusted for use in a Japanese population. One-way and probabilistic sensitivity analyses (OWSA and PSA) were conducted on all inputs and key modeling assumptions.

RESULTS
Dulaglutide 0.75 mg was associated with higher quality-adjusted life years (QALYs), life years (LYs), and total costs, compared to insulin glargine, resulting in an incremental cost-effectiveness ratio (ICER) of 416,280 JPY/QALY gained. Treatment with dulaglutide increased the time alive and free from diabetes-related complications by 4 months. OWSA and PSA indicated that results were robust to plausible variations in input parameters and modeling assumptions.

LIMITATIONS
Key limitations of this study are similar to other cost-utility analyses of diabetes, including the extrapolation of short-term clinical trial data into lifelong durations. In addition, due to the lack of robust published Japanese data, some values were derived from non-Japanese sources.

CONCLUSIONS
This analysis suggests that dulaglutide 0.75 mg may be a cost-effective treatment alternative to insulin glargine for patients with T2DM in Japan.

Ishii|Hitoshi|H| Madin-Warburton|Matthew|M| Strizek|Alena|A| Thornton-Jones|Lucy|L| Suzuki|Shuichi|S|

D000328:Adult
D000368:Aged
D015992:Body Mass Index
D003362:Cost-Benefit Analysis
D048909:Diabetes Complications
D003924:Diabetes Mellitus, Type 2
D018450:Disease Progression
D005260:Female
D004763:Glucagon-Like Peptides
D006442:Glycated Hemoglobin A
D015438:Health Behavior
D005102:Health Expenditures
D006801:Humans
D007004:Hypoglycemic Agents
D007141:Immunoglobulin Fc Fragments
D000069036:Insulin Glargine
D007564:Japan
D008017:Life Expectancy
D008055:Lipids
D008297:Male
D008875:Middle Aged
D017059:Models, Econometric
D011788:Quality of Life
D019057:Quality-Adjusted Life Years
D011993:Recombinant Fusion Proteins

cost-effectiveness
dulaglutide
insulin glargine
Type 2 diabetes
Japan


Centromeres Transcription and Transcripts for Better and for Worse.

Abstract: Centromeres are chromosomal regions that are essential for the faithful transmission of genetic material through each cell division. They represent the chromosomal platform on which assembles a protein complex, the kinetochore, which mediates attachment to the mitotic spindle. In most organisms, centromeres assemble on large arrays of tandem satellite repeats, although their DNA sequences and organization are highly divergent among species. It has become evident that centromeres are not defined by underlying DNA sequences, but are instead epigenetically defined by the deposition of the centromere-specific histone H3 variant, CENP-A. In addition, and although long regarded as silent chromosomal loci, centromeres are in fact transcriptionally competent in most species, yet at low levels in normal somatic cells, but where the resulting transcripts participate in centromere architecture, identity, and function. In this chapter, we discuss the various roles proposed for centromere transcription and their transcripts, and the potential molecular mechanisms involved. We also discuss pathological cases in which unscheduled transcription of centromeric repeats or aberrant accumulation of their transcripts are pathological signatures of chromosomal instability diseases. In sum, tight regulation of centromeric satellite repeats transcription is critical for healthy development and tissue homeostasis, and thus prevents the emergence of disease states.

Centromere
Transcription
Cancer
ICF syndrome
Satellite DNA


Co-treatment of waste smelting slags and gypsum wastes via reductive-sulfurizing smelting for valuable metals recovery.

Abstract: In this work, a new innovative slag cleaning technique was presented to economically and environmentally friendly recover valuable metals from cobalt-bearing copper smelter slag. CaSO4-rich gypsum waste was used as sulfurizing agent to efficiently and selectively sulfurize and recover valuable metals lost in the slag at reductive atmosphere. Thermodynamic analysis and laboratory experiments were carried out to determine the feasibility and reliability of this new process. The optimum slag cleaning conditions were determined as follow: reductive agent coke dosage of 12%, 20% CaSO4 addition of smelter slag weight, smelting at 1350°C for 3h. Under the optimum conditions, 92.04% Cu and 95.62% Co were enriched and recovered in copper-cobalt matte. The contents of Cu and Co in cleaned slag dropped to levels lower than 0.2% and 0.045% respectively. Selectivity recovery ratio of Cu/Fe and Co/Fe can reach 6.00 and 6.24 respectively. Calcium-rich and iron-poor cleaned slag property was more beneficial for minimizing cobalt and copper losses in slag. The products were characterized by XRD and SEM-EDS techniques. The Cu-Co matte primarily comprised iron sulphide (FeS), geerite (Cu8S5), iron cobalt sulphide (Fe0.92Co0.08S), independent cobalt sulphide (CoS) and some metallic Cu, Co and Fe. Copper and cobalt in resultant matte attended to appear separately in different mineral phases. The cleaned slag mainly contained fayalite (Fe2SiO4), hedenbergite (CaFeSi2O6) and magnetite (Fe3O4).

Li|Yun|Y| Chen|Yongming|Y| Tang|Chaobo|C| Yang|Shenghai|S| He|Jing|J| Tang|Motang|M|

Gypsum waste
Reductive-sulfurizing smelting
Slag cleaning
Sulfurizing agent
Recovery of Cu and Co


Bone reconstruction in rat calvarial defects by chitosan/hydroxyapatite nanoparticles scaffold loaded with unrestricted somatic stem cells.

Abstract: Calcium phosphates are one of the biomaterials that are used for bone regeneration. In this study, Hydroxyapatite (HAp) nanoparticles with chitosan gel filled with unrestricted somatic stem cells (USSCs) were used for healing calvarial bone in rat model. The healing effects of these injectable scaffolds with and without stem cells for bone regeneration were investigated by computed tomography (CT) analysis and pathology assays after 28 days of grafting. The results of CT analysis showing bone regeneration on the scaffolds, also the amounts of regenerated new bone for USSC scaffold was significantly greater than the scaffold without cell and untreated controls. Therefore, the combination of scaffold especially with USSC is considered as a useful method for bone regeneration.

Biazar|Esmaeil|E|
Heidari Keshel|Saeed|S|
Tavirani|Mostafa Rezaei|MR|
Jahandideh|Rahim|R|

chitosan
hydroxyapatite nanoparticles
unrestricted somatic stem cells
bone regeneration
injectable scaffold


Investigation of Histone Lysine-Specific Demethylase 5D KDM5D) Isoform Expression in Prostate Cancer Cell Lines: a System Approach.

Abstract:
BACKGROUND
It is now well-demonstrated that histone demethylases play an important role in developmental controls, cell-fate decisions, and a variety of diseases such as cancer. Lysine-specific demethylase 5D (KDM5D) is a male-specific histone demethylase that specifically demethylates di- and tri-methyl H3K4 at the start site of active gene. In this light, the aim of this study was to investigate isoform/transcript-specific expression profiles of KDM5D in three prostate cancer cell lines, Du-145, LNCaP, and PC3.

METHODS
Real-time PCR analysis was performed to determine the expression levels of different KDM5D transcripts in the prostate cell lines. A gene regulatory network was established to analyze the gene expression profile.

RESULTS
Significantly different expression levels of both isoforms were found among the three cell lines. Interestingly, isoform I was expressed in three cell lines while isoform III did only in DU-145. The expression levels of both isoforms were higher in DU-145 when compared to other cell lines (P<0.0001). The observed expression profile was determined by using regulatory network analyses.

CONCLUSION
The present study, for the first time, not only showed the expression profiles of KDM5D isoforms in prostate cancer cell lines but also evaluated the effects of the gene regulatory network on the expression profile of this gene.

D015971:Gene Expression Regulation, Enzymologic

D015972:Gene Expression Regulation, Neoplastic

KDM5D
Prostate cancer
Regulatory networks


Sugarcane Ratooning Ability: Research Status, Shortcomings, and Prospects.

Abstract: Sugarcane is an important sugar crop and it can be subjected to ratooning for several years. The advantages of ratooning include quality improvement, efficiency enhancement, and reduced costs and energy use. The genotype, environment, cultivation management, and harvesting technology affect the productivity and longevity of ratoon cane, with the genetic basis being the most critical factor. However, the majority of research has been focused on only limited genotypes, and a few studies have evaluated up to 100 sugarcane germplasm resources. They mainly focus on the comparison among different genotypes or among plant cane, different selection strategies for the first and second ratoon crops, together with screening indicators for the selection of stronger ratooning ability. In this paper, previous studies are reviewed in order to analyze the importance of sugarcane ratooning, the indicative traits used to evaluate ratooning ability, the major factors influencing the productivity and longevity of ratooning, the genetic basis of variation in ratooning ability, and the underlying mechanisms. Furthermore, the shortcomings of the existing research on sugarcane ratooning are highlighted. We then discuss the focus of future ratoon sugarcane research and the technical methods that will shorten the selection cycle and increase the genetic gain of ratooning ability, particularly the development of linked markers. This review is expected to provide a reference for understanding the mechanisms underlying the formation of ratooning ability and for breeding sugarcane varieties with a strong ratooning ability.

Xu|Fu|F| Wang|Zhoutao|Z| Lu|Guilong|G| Zeng|Rensen|R|0000-0002-6435-3054 Que|Youxiong|Y|

sugarcane ratooning ability
segregating population
sugar production
sugarcane breeding
sugarcane stubble
trait markers


Academic Psychiatry Department Names: Reflections on Research, Practice, and Education.

Abstract:
OBJECTIVE
Medical schools' departments reflect changes in health care and medical school organization. The authors reviewed psychiatry department name categories associated with school age, research, and primary care focus.

METHODS
Department names were identified and categorized for US allopathic and osteopathic medical schools. A multinomial regression model analyzed the relationship between department name category and established year, adjusted for school type. Fisher's exact tests analyzed the relationships between name category and research/primary care foci.

RESULTS
Among 147 allopathic schools, 52% had departments with names limited to psychiatry, 42% had names with psychiatry plus other terminology, and 5% had no identified psychiatry department. In 34 osteopathic schools, 12% had psychiatry departments, 12% had departments named psychiatry plus other terminology, and 75% had no identified psychiatry department. Age of school was related to departmental name: for a 1-year increase in the school's established year, the odds of having a department name other than psychiatry were 1.02 times the odds (p < 0.001) of having the name psychiatry. Newer schools were less likely to have departments with "psychiatry" in their name. Associations were found between department name and research and primary care rankings.

CONCLUSIONS
Variability in the names of psychiatry departments in medical schools may suggest changing views within and about academic psychiatry. The limited presence of formal psychiatry departments in newer schools raises questions about psychiatry's impact on educational pathways, the future workforce, and participation in schools' research mission and clinical enterprise.

Psychiatry department
Administration
Psychiatry trends


Distal 22q11.2 microduplication combined with typical 22q11.2 proximal deletion: a case report.

Abstract: The 22q11 chromosomal region contains low copy repeats (LCRs) sequences that mediate non-allelic homologous recombination, which predisposes to copy number variations (CNVs) at this locus. Hemizygous deletions of the proximal 22q11.2 region result in the 22q11.2 deletion syndrome (22q11.2 DS). In addition, 22q11.2 duplications involving the distal LCR22s have been reported. This article describes a patient presenting a 2.5-Mb de novo deletion at proximal 22q11.21 region (between LCRs A-D), combined with a 1.3-Mb maternally inherited duplication at distal 22q11.23 region (between LCRs F-H). The presence of concomitant chromosomal imbalances found in this patient has not been reported previously. Clinical and molecular data were compared with literature, in order to contribute to genotype-phenotype correlation. These findings exemplify the complexity and genetic heterogeneity observed in 22q11.2 deletion syndrome and highlights the difficulty to make genetic counseling and predict phenotypic consequences in these situations.

Molck|Miriam Coelho|MC|
Vieira|Társis Paiva|TP|
Simioni|Milena|M|
Sgardioli|Ilária Cristina|IC|
dos Santos|Ana Paula|AP|
Xavier|Ana Carolina|AC|
Gil-da-Silva-Lopes|Vera Lúcia|VL|

copy number variations
22q11.2 deletion
genotype-phenotype correlation
22q11.2 distal duplication


How to Assess Protein Stability: Half-Life Determination of a Regulatory Protein in Bacillus subtilis.

Abstract: The half-life of a particular protein is highly variable, reaching from minutes to hours, over days and weeks to years or even a whole life time of an organism (e.g., α-crystalline of the mammalian eye). Thus, controlling protein activity by proteolysis is the most dramatic and unambiguous decision by any organism, because reconstitution of the destroyed protein activity requires an "expensive" new synthesis. To distinguish degradation from protein synthesis and accumulation only one method comes into consideration-pulse-chase labeling. In our hands, the most accurate method to track the fate of a single protein is radioactive pulse-chase labeling combined with immunoprecipitation. Besides a detailed description of the standard protocol, the general applicability as well as certain improvements of the method will be discussed here.

D000255:Adenosine Triphosphate
D001412:Bacillus subtilis
D001426:Bacterial Proteins
D001681:Biological Assay
D047468:Immunoprecipitation
D007553:Isotope Labeling
D055550:Protein Stability
D059748:Proteolysis
D013462:Sulfur Radioisotopes

Regulatory proteins
Bacillus subtilis
Degradation
Immunoprecipitation
ATP-dependent proteolysis


Solubility enhancement of dioxins and PCBs by surfactant monomers and micelles quantified with polymer depletion techniques.

Abstract: Partitioning of super-hydrophobic organic contaminants (SHOCs) to dissolved or colloidal materials such as surfactants can alter their behaviour by enhancing apparent aqueous solubility. Relevant partition constants are, however, challenging to quantify with reasonable accuracy. Partition constants to colloidal surfactants can be measured by introducing a polymer (PDMS) as third phase with known PDMS-water partition constant in combination with the mass balance approach. We quantified partition constants of PCBs and PCDDs (log KOW 5.8-8.3) between water and sodium dodecyl sulphate monomers (KMO) and micelles (KMI). A refined, recently introduced swelling-based polymer loading technique allowed highly precise (4.5-10% RSD) and fast (<24 h) loading of SHOCs into PDMS, and due to the miniaturisation of batch systems equilibrium was reached in <5 days for KMI and <3 weeks for KMO. SHOC losses to experimental surfaces were substantial (8-26%) in monomer solutions, but had a low impact on KMO (0.10-0.16 log units). Log KMO for PCDDs (4.0-5.2) were approximately 2.6 log units lower than respective log KMI, which ranged from 5.2 to 7.0 for PCDDs and 6.6-7.5 for PCBs. The linear relationship between log KMI and log KOW was consistent with more polar and moderately hydrophobic compounds. Apparent solubility increased with increasing hydrophobicity and was highest in micelle solutions. However, this solubility enhancement was also considerable in monomer solutions, up to 200 times for OCDD. Given the pervasive presence of surfactant monomers in typical field scenarios, these data suggest that low surfactant concentrations may be effective long-term facilitators for subsurface transport of SHOCs.

Schacht|Veronika J|VJ|
Grant|Sharon C|SC|
Escher|Beate I|BI|
Hawker|Darryl W|DW|
Gaus|Caroline|C|

D057927:Hydrophobic and Hydrophilic Interactions

Surfactant monomers and micelles
Partition constants
Polychlorinated biphenyls
Polychlorinated dibenzo-p-dioxins
Silanization
poly(dimethylsiloxane)


Infected intradural dermoid cyst without dermal sinus tract mimicking brain abscess: A case report.

Abstract:
INTRODUCTION
Infection is a rare complication of intradural dermoid cyst. We reported an infected intradural dermoid cyst without dermal sinus tract mimicking brain abscess.

PRESENTATION OF CASE
A 4-year-old boy with no medical history complained of a palpable mass on his head. On examination, the occipital palpable mass was firm and immobile, had no redness, swelling, and pain. The preoperative MRI showed a well-defined, ring-enhancing lesion. White blood count was 12.8 × 109  cells/liter. We have sought no other infection sites. We encountered intraoperatively the pus from the infected mass invading subcutaneous layer and skull bone. We excised completely the tumor and carefully coagulated the residual capsule invading superior sagittal sinus. Histopathological examination was infected dermoid cyst. The infection agent was Staphylococcus aureus. The patient was received systemic antibiotic therapy for 21 days following oral antibiotics for 1 month. He was discharged with no complications.

DISCUSSION
The diagnosis of infected dermoid cyst was often based on MRI images and especially dermal sinus tract. However, in the absence of a dermal sinus tract, preoperative diagnosing an infected dermoid cyst might be very challenging. The ideal treatment of the dermoid cyst was total resection of the cyst with the epithelial lining. Nevertheless, due to the benign nature of dermoid cyst, adequate gross total resection with meticulous hemostasis the residual capsule firmly adhering eloquent areas and major vessels was more appropriate.

CONCLUSION
Diagnosing infected dermoid cyst with no dermal sinus might be challenging. Systemic antibiotic therapy after gross total resection was an effective treatment.

Pham|Anh Hoang|AH|
Le|Tam Duc|TD|
Chu|Hung Thanh|HT|
Le|Tuan Anh|TA|
Duong|Ha Dai|HD|
Van Dong|He|H|

Infection
Intradural dermoid cyst
No dermal sinus
Children


Predictive value of CD4 cell count nadir on long-term mortality in HIV-positive patients in Uganda.

Abstract:
OBJECTIVE
Although international guidelines recommend initiating antiretroviral therapy (ART) when a patient's CD4 cell count is ≤350 cells/μL, most patients in resource-limited settings present with much lower CD4 cell counts. The lowest level that their CD4 cell count reaches, the nadir, may have long-term consequences in terms of mortality. We examined this health state in a large cohort of HIV+ patients in Uganda.

DESIGN
This was an observational study of HIV patients in Uganda aged 14 years or older, who were enrolled in 10 major clinics across Uganda.

METHODS
We assessed the CD4 nadir of patients, using their CD4 cell count at initiation of ART, stratified into categories (,50, 50-99, 100-149, 150-249, 250+ cells/μL). We constructed Kaplan-Meier curves to assess the differences in survivorship for patients left-censored at 1 year and 2 years after treatment initiation. We used Cox proportional hazards regression to model the associations between CD4 nadir and mortality. We adjusted mortality for loss-to-follow-up.

RESULTS
Of 22,315 patients, 20,129 patients had greater than 1 year of treatment follow-up. Among these patients, 327 (1.6%) died and 444 (2.2%) were lost to follow-up. After left-censoring at one year, relative to lowest CD4 strata, patients with higher CD4 counts had significantly lower rates of mortality (CD4 150-249, hazard ratio [HR] 0.60, 95% confidence interval [CI]: 0.45-0.82, P = 0.001; 250+, HR 0.66, 95% CI, 0.44-1.00, P = -0.05). Male sex, older age, and duration of time on ART were independently associated with mortality. When left-censoring at 2 years, CD4 nadir was no longer statistically significantly associated with mortality.

CONCLUSION
After surviving for 1 year on ART, a CD4 nadir was strongly predictive of longer-term mortality among patients in Uganda. This should argue for efforts to increase engagement with patients to ensure a higher CD4 nadir at initiation of treatment.

Bray|Sarah|S|
Gedeon|Jillian|J|
Hadi|Ahsan|A|
Kotb|Ahmed|A|
Rahman|Tarun|T|
Sarwar|Elaha|E|
Savelyeva|Anna|A|
Sévigny|Marika|M|
Bakanda|Celestin|C|
Birungi|Josephine|J|
Chan|Keith|K|
Yaya|Sanni|S|
Deonandan|Raywat|R|
Mills|Edward J|EJ|

CD4
antiretroviral therapy
ART
prognosis
sub-Saharan Africa


Distribution and antimicrobial resistance profile of bacteria recovered from sewage system of health institutions found in Hawassa, Sidama Regional State, Ethiopia: A descriptive study.

Abstract:
Objectives
The aim of the study was to determine the distribution and antimicrobial susceptibility profile of bacteria recovered from the sewage systems of health institutions found in Hawassa, Sidama Regional State, Ethiopia.

Methods
A cross-sectional study was conducted from 20 October 2020 to 1 December 2020. A total of 27 sewage samples were collected at two points, namely, before entering the septic tank and from the septic tank of seven health institutions. Samples were inoculated onto Mannitol salt agar, Blood agar, and MacConkey agar, and incubated for 24 h at 37°C. Bacteria were identified using colony morphology, Gram staining, and biochemical tests. An antimicrobial susceptibility test was performed using the Kirby-Bauer disk diffusion method. Data were analyzed by SPSS, version 25, and results were presented in text and tables.

Results
All sewage samples (n = 27) examined in the current study contained potential pathogenic bacteria. Overall, 129 different types of bacteria were identified. Of isolated bacteria, 14 (10.8%) were Gram positive, while 115 (89.2%) were Gram negative. The most prevalent bacteria were Escherichia coli (n = 27, 20.9%) followed by Shigella species (n = 26, 20.2%), Pseudomonas species (n = 25, 19.4%), Salmonella species (n = 25, 19.4%), Staphylococcus aureus (n = 14, 10.9%), and Klebsiella species (n = 12, 9.3%). All bacteria were susceptible to azithromycin. About 80% of bacteria were resistant to ampicillin, whereas greater than 80% of bacteria were susceptible to norfloxacin, ciprofloxacin, and gentamicin.

Conclusion
All sewage systems of health institutions included in the current study contained different types of pathogenic bacteria, which are resistant to commonly prescribed antibiotics.

antimicrobial susceptibility profile
Antibiotic resistance
bacterial distribution
health facilities


Factors associated with visual recovery after sub-Tenon injection of triamcinolone acetonide in diabetic macular edema.

Abstract:
BACKGROUND
The purpose of this retrospective chart review was to evaluate factors associated with improvement of visual acuity after a single sub-Tenon injection of triamcinolone acetonide in patients with diabetic macular edema.

METHODS
We reviewed the medical records for 63 consecutive eyes with diabetic macular edema treated by sub-Tenon injection of triamcinolone acetonide and assessed at 2 months postoperatively. We evaluated changes in morphology, foveal photoreceptor status, and parafoveal cystic change, and also measured the central retinal thickness and macular volume. The association of these factors with improvement of vision (logarithm of the minimum angle of resolution, logMAR) was investigated.

RESULTS
Eyes were classified as having cystoid macular edema (CME, n = 52), serous retinal detachment (n = 24), or diffuse diabetic macular edema (n = 4). In eyes with CME, the mean logMAR of visual acuity improved significantly (P = 0.003) from 0.35 ± 0.31 at baseline to 0.29 ± 0.29 after 2 months. However, there was no significant improvement of visual acuity in the eyes with serous retinal detachment or diffuse diabetic macular edema after sub-Tenon injection of triamcinolone acetonide (P = 0.549 and P = 0.545, respectively). The central retinal thickness and macular volume were both reduced significantly after sub-Tenon injection of triamcinolone acetonide in eyes with CME and serous retinal detachment. However, improvement of visual acuity in the eyes with CME was not correlated with the reduction of central retinal thickness or macular volume. Parafoveal cystic changes showed significant improvement after sub-Tenon injection of triamcinolone acetonide in eyes with CME. Photoreceptor status was significantly associated with the visual prognosis in eyes with CME, but not in eyes with serous retinal detachment.

CONCLUSION
Visual acuity improved significantly after sub-Tenon injection of triamcinolone acetonide without photoreceptor recovery in eyes with CME. Improvement of parafoveal cystic changes in the eyes with CME suggests that bipolar cells or their accessory cells might have displayed functional recovery.

sub-Tenon injection
triamcinolone acetonide
diabetic macular edema
cystoid macular edema
external limiting membrane