Topical delivery of paclitaxel for treatment of skin cancer.

Abstract:
CONTEXT
Skin cancer represents the most growing types of cancer in human and ultraviolet radiation can be cited as one of the prime factor for its occurrence. Current therapy of skin cancer suffers from numerous side effects; for effective therapy, topical application of formulation of paclitaxel (PTX) can be considered as a novel approach.

OBJECTIVE
The present study is an attempt to prepare formulation of solid lipid nanoparticles (SLN) of PTX for the effective treatment of various form of skin carcinoma.

METHODS
The SLN were prepared by high-speed homogenization and ultrasonication method. The prepared SLN were characterized. The optimized PTX SLN were loaded in carbopol gel. The prepared gels were evaluated for its gelling properties and finally studied for in vivo anti-cancer efficacy and histopathological study.

RESULTS
The particle size distribution was found to be in the range of 78.82-587.8 nm. The product yield (%) was found between 60% and 66% and showed a highest entrapment efficiency of 68.3%. The in vitro release of the drug from SLN dispersion was found to be biphasic with the initial burst effect, followed by slow release. SLN-loaded gel were subjected to permeability study and the results show steady-state flux (Jss), permeability coefficient (Kp), and enhancement ratio were significantly increased in SLN-loaded gel formulation as compared with PTX-loaded gel. The histopathological study clearly reveals the efficacy of the SLN-F3 3G in the treatment of skin cancer.

CONCLUSION
The experimental formulations show controlled release of PTX and thus expected to show reduce dose-related side effects.

Bharadwaj|Rituraj|R|
Das|Pranab Jyoti|PJ|
Pal|Paulami|P|
Mazumder|Bhaskar|B|

paclitaxel
Lipid
nanoparticles
skin carcinoma
permeability


Pre-analytical issues in the haemostasis laboratory: guidance for the clinical laboratories.

Abstract: Ensuring quality has become a daily requirement in laboratories. In haemostasis, even more than in other disciplines of biology, quality is determined by a pre-analytical step that encompasses all procedures, starting with the formulation of the medical question, and includes patient preparation, sample collection, handling, transportation, processing, and storage until time of analysis. This step, based on a variety of manual activities, is the most vulnerable part of the total testing process and is a major component of the reliability and validity of results in haemostasis and constitutes the most important source of erroneous or un-interpretable results. Pre-analytical errors may occur throughout the testing process and arise from unsuitable, inappropriate or wrongly handled procedures. Problems may arise during the collection of blood specimens such as misidentification of the sample, use of inadequate devices or needles, incorrect order of draw, prolonged tourniquet placing, unsuccessful attempts to locate the vein, incorrect use of additive tubes, collection of unsuitable samples for quality or quantity, inappropriate mixing of a sample, etc. Some factors can alter the result of a sample constituent after collection during transportation, preparation and storage. Laboratory errors can often have serious adverse consequences. Lack of standardized procedures for sample collection accounts for most of the errors encountered within the total testing process. They can also have clinical consequences as well as a significant impact on patient care, especially those related to specialized tests as these are often considered as "diagnostic". Controlling pre-analytical variables is critical since this has a direct influence on the quality of results and on their clinical reliability. The accurate standardization of the pre-analytical phase is of pivotal importance for achieving reliable results of coagulation tests and should reduce the side effects of the influence factors. This review is a summary of the most important recommendations regarding the importance of pre-analytical factors for coagulation testing and should be a tool to increase awareness about the importance of pre-analytical factors for coagulation testing.

Magnette|A|A|
Chatelain|M|M|
Chatelain|B|B|
Ten Cate|H|H|
Mullier|F|F|0000-0001-6947-6099

Pre-analytical phase
Recommendations
Centrifugation
Coagulation assays
Dabigatran
Haemostasis assays
Idarucizumab
Microparticles


Acute Respiratory Failure Is the Initial Manifestation in the Adult-Onset A3243G tRNALeu mtDNA Mutation: A Case Report and the Literature Review.

Abstract: Isolated mitochondrial myopathy refers to the condition of mitochondrial disorders that primarily affect the skeletal muscle system. Here we report on a case of a patient who presented with acute respiratory failure as the initial and predominant clinical manifestation after using anesthetic drugs. The diagnosis of mitochondrial myopathy was made by histochemical findings of ragged red fibers with a modified Gomori trichrome Stain in the skeletal muscle biopsy and the genetic detection of an A3243G point mutation in the tRNALeu (UUR) gene of mitochondrial DNA (mtDNA) in a peripheral blood specimen. The patient revealed a benign clinical outcome with ventilator assistance and a cocktail treatment. Further, we performed a literature review on patients with respiratory failure as the early and predominant manifestation in adult-onset isolated mitochondrial myopathy. Eleven cases in nine studies (including our case) have been reported, and five of whom underwent DNA analysis all harbored the A3243G mutation in the tRNALeu gene of the mtDNA. Use of sedative drugs tends to induce acute respiratory failure in such cases.

Pan|Xiaoli|X| Wang|Lijun|L| Fei|Guoqiang|G| Dong|Jihong|J| Zhong|Chunjiu|C| Lu|Jiahong|J| Jin|Lirong|L|

respiratory failure
mtDNA
mitochondrial myopathy
A3243G mutation
sedative drug


Gut Bacteria and Hydrogen Sulfide: The New Old Players in Circulatory System Homeostasis.

Abstract: Accumulating evidence suggests that gut bacteria play a role in homeostasis of the circulatory system in mammals. First, gut bacteria may affect the nervous control of the circulatory system via the sensory fibres of the enteric nervous system. Second, gut bacteria-derived metabolites may cross the gut-blood barrier and target blood vessels, the heart and other organs involved in the regulation of the circulatory system. A number of studies have shown that hydrogen sulfide (H₂S) is an important biological mediator in the circulatory system. Thus far, research has focused on the effects of H₂S enzymatically produced by cardiovascular tissues. However, some recent evidence indicates that H₂S released in the colon may also contribute to the control of arterial blood pressure. Incidentally, sulfate-reducing bacteria are ubiquitous in mammalian colon, and H₂S is just one among a number of molecules produced by the gut flora. Other gut bacteria-derived compounds that may affect the circulatory system include methane, nitric oxide, carbon monoxide, trimethylamine or indole. In this paper, we review studies that imply a role of gut microbiota and their metabolites, such as H₂S, in circulatory system homeostasis.

gut bacteria
hydrogen sulfide
indole
microbiota
TMAO
cardiovascular diseases
hypertension
sulfur


The use of invertebrate body burdens to predict ecological effects of metal mixtures in mining-impacted waters.

Abstract: The present study investigated whether invertebrate body burdens can be used to predict metal-induced effects on aquatic invertebrate communities. Total dissolved metal levels and four invertebrate taxa (Leuctra sp., Simuliidae, Rhithrogena sp. and Perlodidae) were sampled in 36 headwater streams located in the north-west part of England. Using the River Invertebrate Prediction and Classification System (RIVPACS) taxonomic completeness of invertebrate communities was assessed. Quantile regression was used to relate invertebrate body burdens to a maximum (90th quantile) ecological response, both for all metals separately and in mixtures. Significant relations between Cu, Zn and Pb burdens in Leuctra sp. (Zn, Pb), Simuliidae (Zn, Pb), Rhithrogena sp. (Cu, Zn, Cu+Zn) and Perlodidae (Zn) and both taxonomic completeness (O/E taxa) and Biological Monitoring Working Party index scores (O/E BMWP) were observed. Correspondingly the obtained Cu-Zn mixture model an acceptable impact of 5% change in taxonomic completeness is expected at Rhithrogena sp. body burdens of 1.9μmolg(-1) Cu (121 μg g(-1) Cu) in case of low Zn bioavailability (Rhithrogena sp. Zn body burden of 2.9 μmol g(-1) or 190 μg g(-1)), which will drop to 0.30 μmol g(-1) Cu (19.1 μg g(-1) Cu) in case of higher Zn bioavailability (Zn body burden of 72.6 μmol g(-1) or 4747 μg g(-1)). For Zn, 5% change in taxonomic completeness is expected at Rhithrogena sp. body burdens of 76.4 μmol g(-1) Zn (4995 μg g(-1) Zn) in case of low Cu bioavailability (Cu body burden of 0.19 μmol g(-1) or 12.1 μg g(-1)), which will drop to 6.6 μmol g(-1) Zn (432 μg g(-1) Zn) at higher Cu bioavailability (Cu body burden of 1.74 μmol g(-1) or 111 μg g(-1)). Overall, the present study concludes that invertebrate body burdens can be used to (1) predict metal-induced ecological effects and (2) to derive critical burdens for the protection of aquatic invertebrate communities.

De Jonge|Maarten|M|
Tipping|Edward|E|
Lofts|Stephen|S|
Bervoets|Lieven|L|
Blust|Ronny|R|

Invertebrate body burdens
Metal mixtures
Quantile regression
Aquatic ecology
Macroinvertebrate community


Rheological Differences of Waxy Barley Flour Dispersions Mixed with Various Gums.

Abstract: Rheological properties of waxy barley flour (WBF) dispersions mixed with various gums (carboxyl methyl celluleose, guar gum, gum arabic, konjac gum, locust bean gum, tara gum, and xanthan gum) at different gum concentrations were examined in steady and dynamic shear. WBF-gum mixture samples showed a clear trend of shear-thinning behavior and had a non-Newtonian nature with yield stress. Rheological tests indicated that the flow and dynamic rheological parameter (apparent viscosity, consistency index, yield stress, storage modulus, and loss modulus) values of WBF dispersions mixed with gums, except for gum arabic, were significantly higher than those of WBF with no gum, and also increased with an increase in gum concentration. In particular, konjac gum at 0.6% among other gums showed the highest rheological parameter values. Tan δ values of WBF-xanthan gum mixtures were lower than those of other gums, showing that there is a more pronounced synergistic effect on the elastic properties of WBF in the presence of xanthan gum. Such synergistic effect was hypothesized by considering thermodynamic compatibility between xanthan gum and WBF. These rheological results suggest that in the WBF-gum mixture systems, the addition of gums modified the flow and viscoelastic properties of WBF, and that these modifications were dependent on the type of gum and gum concentration.

waxy barley flour
gum
rheological property
synergistic effect
viscoelastic property


Hybrid Nanoparticle Pyramids for Intracellular Dual MicroRNAs Biosensing and Bioimaging.

Abstract: This study strategically fabricates multifunctional nanopyramids to allow the ultrasensitive quantification of dual microRNAs (miR-203b and miR-21) in living cells and their responsive bioimaging in vivo. The nanopyramids, composed of Au-Cu9 S5 nanoparticles (NPs), upconversion NPs (UCNPs), and Ag2 S NPs, emit two luminescent signals simultaneously with excitation at 808 nm, arising from the UCNPs at 541 nm in the visible region and from the Ag2 S NPs at 1227 nm in the second window of near-infrared (NIR-II) region. The upconversion luminescence has a linear relationship with miR-203b from 0.13 to 54.54 fmol per 10 µgRNA and a limit of detection (LOD) of 0.09 fmol per 10 µgRNA , whereas the Ag2 S NP luminescence has a linear relationship with miR-21 from 0.37 to 43.56 fmol per 10 µgRNA , with a LOD of 0.23 fmol per 10 µgRNA . Significantly, this study demonstrates that the nanopyramids can be successfully used for miRs-responsive bioimaging in a tumor-bearing animal model. Furthermore, taking advantage of the photothermal capabilities of pyramids, the tumors can also be eliminated completely. These nanopyramids not only overcome the obstacles in the simultaneous detection of multiple miRs at the cellular level but also provide a cancer theranostic platform in vivo.

Li|Si|S| Xu|Liguang|L| Sun|Maozhong|M| Wu|Xiaoling|X| Liu|Liqiang|L| Kuang|Hua|H| Xu|Chuanlai|C|

hybrid nanoparticle pyramids
intracellular dual microRNAs
biosensing
bioimaging
tumor ablation


Sol-Gel Chemistry for Carbon Dots.

Abstract: Carbon dots are an emerging class of carbon-based nanostructures produced by low-cost raw materials which exhibit a widely-tunable photoluminescence and a high quantum yield. The potential of these nanomaterials as a substitute of semiconductor quantum dots in optoelectronics and biomedicine is very high, however they need a customized chemistry to be integrated in host-guest systems or functionalized in core-shell structures. This review is focused on recent advances of the sol-gel chemistry applied to the C-dots technology. The surface modification, the fine tailoring of the chemical composition and the embedding into a complex nanostructured material are the main targets of combining sol-gel processing with C-dots chemistry. In addition, the synergistic effect of the sol-gel precursor combined with the C-dots contribute to modify the intrinsic chemo-physical properties of the dots, empowering the emission efficiency or enabling the tuning of the photoluminescence over a wide range of the visible spectrum.

carbon dots
sol-gel processes
fluorescent probes
sensors


Implementation of a self-monitoring application to improve on-task behavior: A high school pilot study.

Abstract: Technological innovations offer promise for improving intervention implementation in secondary, inclusive classrooms. A withdrawal design was employed with two high school students in order to assess the effectiveness of a technologically-delivered, self-monitoring intervention in improving on-task behavior in a science classroom. Two students ages 14 and 15 with diagnoses of specific learning disability (student 1) and attention deficit hyperactivity disorder (ADHD: student 2) were selected by case manager referral due to difficulties with on-task behavior despite long-term administration of psychostimulant medication. After baseline data were collected, both students were trained in the use of a self-monitoring application (I-Connect) delivered via a handheld tablet. On-task prompts were delivered at five min intervals in an ABAB withdrawal design. The intervention resulted in positive, stable improvements in the primary dependent variable of on-task behavior for both students and less clear improvement in the generalization variable of disruptive behavior.

high school
intervention
emotional/behavioral disorders
self management
self monitoring


Sphingolipids in early viral replication and innate immune activation.

Abstract: In this review, we summarize the mechanisms by which sphingolipids modulate virus multiplication and the host innate immune response, using a number of host-virus systems as illustrative models. Sphingolipids exert diverse functions, both at the level of the viral life cycle and in the regulation of antiviral immune responses. Sphingolipids may influence viral replication in three ways: by serving as (co)receptors during viral entry, by modulating virus replication, and by shaping the antiviral immune response. Several studies have demonstrated that sphingosine kinases (SphK) and their product, sphingosine-1-phosphate (S1P), enhance the replication of influenza, measles, and hepatitis B virus (HBV). In contrast, ceramides, particularly S1P and SphK1, influence the expression of type I interferon (IFN-I) by modulating upstream antiviral signaling and enhancing dendritic cell maturation, differentiation, and positioning in tissue. The synthetic molecule α-galactosylceramide has also been shown to stimulate natural killer cell activation and interferon (IFN)-γ secretion. However, to date, clinical trials have failed to demonstrate any clinical benefit for sphingolipids in the treatment of cancer or HBV infection. Taken together, these findings show that sphingolipids play an important and underappreciated role in the control of virus replication and the innate immune response.

Bezgovsek|Judith|J|
Gulbins|Erich|E|
Friedrich|Sarah-Kim|SK|
Lang|Karl S|KS|
Duhan|Vikas|V|

sphingolipids
innate immune response
sphingosine kinase
viral infection


Competitive inhibition of the high-affinity choline transporter by tetrahydropyrimidine anthelmintics.

Abstract: The high-affinity choline transporter CHT1 mediates choline uptake, the rate-limiting and regulatory step in acetylcholine synthesis at cholinergic presynaptic terminals. CHT1-medated choline uptake is specifically inhibited by hemicholinium-3, which is a type of choline analog that acts as a competitive inhibitor. Although the substrate choline and the inhibitor hemicholinium-3 are well-established ligands of CHT1, few potent ligands other than choline analogs have been reported. Here we show that tetrahydropyrimidine anthelmintics, known as nicotinic acetylcholine receptor agonists, act as competitive inhibitors of CHT1. A ligand-dependent trafficking assay in cell lines expressing human CHT1 was designed to search for CHT1 ligands from a collection of biologically active compounds. We found that morantel as well as other tetrahydropyrimidines, pyrantel and oxantel, potently inhibits the high-affinity choline uptake activity of CHT1 in a competitive manner similar to the inhibitor hemicholinium-3. They also inhibit the high-affinity choline transporter from the nematode Caenorhabditis elegans. Finally, tetrahydropyrimidines potently inhibit the high-affinity choline uptake in rat brain synaptosomes at a low micromolar level, resulting in the inhibition of acetylcholine synthesis. The rank order of potency in synaptosomes is as follows: morantel > pyarantel > oxantel (Ki = 1.3, 5.7, and 8.3 μM, respectively). Our results reveal that tetrahydropyrimidine anthelmintics are novel CHT1 ligands that inhibit the high-affinity choline uptake for acetylcholine synthesis in cholinergic neurons.

Okuda|Takashi|T| Nomura|Yuki|Y| Konishi|Asami|A| Misawa|Hidemi|H|

High-affinity choline transporter
Tetrahydropyrimidine anthelmintics
CHT1
Acetylcholine
Competitive inhibitor
Ligand screening


Plasma Circulating Cell-free DNA Integrity as a Promising Biomarker for Diagnosis and Surveillance in Patients with Hepatocellular Carcinoma.

Abstract: The clinical significance of circulating cell-free DNA (cfDNA) integrity as diagnostic and surveillance biomarker in hepatocellular carcinoma (HCC) was investigated and compared to that of alpha fetoprotein (AFP). Liver cancer patients had lower cfDNA integrity than those with benign diseases (P = 0.0167) and healthy individuals (P = 0.0025). Patients with HCC and non-HCC liver cancers (P = 0.7356), and patients with benign diseases and healthy individuals (P = 0.9138) had comparable cfDNA integrity respectively. cfDNA integrity increased after hepatectomy in cancer patients (P = 0.0003). The AUCs for detecting HCC by cfDNA integrity and AFP were 0.705 (P = 0.005) and 0.605 (P = 0.156), respectively. We found cfDNA integrity decreased in HCC patients and has the potential as promising biomarker for HCC diagnosis and treatment surveillance.

Huang|Ao|A| Zhang|Xin|X| Zhou|Shao-Lai|SL| Cao|Ya|Y| Huang|Xiao-Wu|XW| Fan|Jia|J| Yang|Xin-Rong|XR| Zhou|Jian|J|

circulating cell-free DNA
integrity
cfDNA
hepatocellular carcinoma.


3D QSAR studies of hydroxylated polychlorinated biphenyls as potential xenoestrogens.

Abstract: Mono-hydroxylated polychlorinated biphenyls (OH-PCBs) are found in human biological samples and lack of data on their potential estrogenic activity has been a source of concern. We have extended our previous in silico 2D QSAR study through the application of advance techniques such as docking and 3D QSAR to gain insights into their estrogen receptor (ERα) binding. The results support our earlier findings that the hydroxyl group is the most important feature on the compounds; its position, orientation and surroundings in the structure are influential for the binding of OH-PCBs to ERα. This study has also revealed the following additional interactions that influence estrogenicity of these chemicals (a) the aromatic interactions of the biphenyl moieties with the receptor, (b) hydrogen bonding interactions of the p-hydroxyl group with key amino acids ARG394 and GLU353, (c) low or no electronegative substitution at para-positions of the p-hydroxyl group, (d) enhanced electrostatic interactions at the meta position on the B ring, and (e) co-planarity of the hydroxyl group on the A ring. In combination the 2D and 3D QSAR approaches have led us to the support conclusion that the hydroxyl group is the most important feature on the OH-PCB influencing the binding to estrogen receptors, and have enhanced our understanding of the mechanistic details of estrogenicity of this class of chemicals. Such in silico computational methods could serve as useful tools in risk assessment of chemicals.

Ruiz|Patricia|P|
Ingale|Kundan|K|
Wheeler|John S|JS|
Mumtaz|Moiz|M|

3D QSAR
OH-PCBs
2D QSAR
In silico modeling
kNN MFA


The role of testosterone in menopausal hormone treatment. What is the evidence?

Abstract: About 40% of postmenopausal women have decreased sexual desire, causing distress. Estrogen therapy attenuates vaginal complaints but has no effect on sexual desire. Although sexual function has been linked to testosterone, there is no clear relation between sexual desire and circulating levels of testosterone. Nevertheless, treatment with transdermal (patch) testosterone improved sexual function in several randomized controlled trials. Women with hypoactive sexual desire disorder who were treated with testosterone reported more satisfying sexual episodes and sexual desire compared with the placebo group. Adverse effects were mild. However, there is no testosterone drug designed for women available on the European market. Consequently, women who opt for testosterone treatment have to use preparations made for men with a high drug concentration. Adequate dosage for women is therefore challenging. A trial of 5 mg transdermal testosterone (gel or cream) daily or less has been suggested, followed by close monitoring of side effects and hormone level.

Johansen|Nora|N|
Lindén Hirschberg|Angelica|A|
Moen|Mette H|MH|0000-0001-6013-2409

testosterone
menopause
drug treatment
practice guidelines as topic
sexual dysfunction


Perioperative outcome of elderly versus younger patients undergoing major hepatic or pancreatic surgery.

Abstract:
Objective
The aim of this study was to determine the safety of elderly cancer patients (≥70 years) undergoing hepatic resection (HR) or pancreaticoduodenectomy (PD) in comparison with younger adults (<70 years).

Methods
A total of 1,012 consecutive patients undergoing HR or PD were included. The incidence and severity of morbidity were documented within 30 days postoperatively and compared between elderly and younger groups. Risk factors associated with postoperative morbidity were investigated by multivariate logistic regression analysis.

Results
Elderly patients (n=111, 11.0%) had more comorbidities and worse preoperative general condition and liver function versus younger patients (n=901, 89.0%), and thus were more likely to develop infectious (eg, systemic sepsis and urinary tract infection, both p<0.01) and technical-associated complications (intraperitoneal bleeding and biliary/pancreatic fistula, p=0.029 and p=0.074, respectively). However, the incidence and severity of complications were comparable between elderly and younger patients in the whole cohort, and also in HR and PD surgery groups separately. Preoperative hemoglobin (odds ratio [OR] 1.4, p=0.007) and intraoperative blood transfusion (OR 1.9, p=0.002), rather than age, were independently associated with postoperative morbidity. Hepatitis (OR 2.9, p=0.001), preoperative hemoglobin (OR 1.6, p=0.036), and pancreatic versus hepatic surgery (OR 2.3, p=0.005) were independently associated with postoperative infectious. For elderly patients only, American Society of Anesthesiologists (ASA) score III (OR 2.1, p=0.033) and intraoperative blood transfusion (OR 3.2, p=0.030) were independently associated with postoperative morbidity.

Conclusion
HR and PD can be safely performed in selected elderly patients versus younger patients. Elderly patients with ASA score III or above should be cautiously selected for major surgeries.

Lu|Qiang|Q| Lu|Jian-Wen|JW| Wu|Zheng|Z| Liu|Xue-Min|XM| Li|Jian-Hui|JH| Dong|Jian|J| Yin|Guo-Zhi|GZ| Lv|Yi|Y| Zhang|Xu-Feng|XF|

elderly pancreaticoduodenectomy morbidity hepatectomy


Mitochondria-Localized Fluorescent BODIPY-Platinum Conjugate.

Abstract: A convenient synthesis of a BODIPY (1,3,5,7-tetramethyl-8-(4-pyridyl)-4,4'-difluoroboradiazaindacene) labeled platinum compound (BODIPY-Pt) was developed by direct conjugation of cisplatin with the pyridine group of BODIPY. The membrane permeability and selective uptake of BODIPY-Pt in the mitochondria was studied using confocal laser scanning microscopy (CLSM). The fluorescent BODIPY-Pt conjugate showed high cellular proliferation inhibition against human cervical carcinoma (HeLa) and human breast cancer (MCF-7) cells, with half maximal inhibitory concentrations (IC50) of 27.37 and 12.14 μM, respectively. This work highlights the potential of using BODIPY labeled Pt compounds to realize the visualization of Pt distribution in living cells.

Sun|Tingting|T| Guan|Xingang|X| Zheng|Min|M| Jing|Xiabin|X| Xie|Zhigang|Z|


Multiplex Real-time Polymerase Chain Reaction Assays for Simultaneous Detection of Vibrio cholerae, Vibrio parahaemolyticus, and Vibrio vulnificus.

Abstract:
OBJECTIVES
A multiplex real-time polymerase chain reaction (RT-PCR) method was developed for the identification of three Vibrio species: Vibrio cholerae, Vibrio parahaemolyticus, and Vibrio vulnificus.

METHODS
Specific primers and probes targeting the hlyA, tlh, and vvhA genes were selected and used for multiplex real-time PCR to confirm the identification of V. cholerae, V. parahaemolyticus, and V. vulnificus, respectively. This method was applied to screen Vibrio species from environmental samples and combining it with a culture-based method, its effectiveness was evaluated in comparison with culture-based methods alone.

RESULTS
Specific PCR fragments were obtained from isolates belonging to the target species, indicating a high specificity of this multiplex real-time PCR. No cross-reactivity with the assay was observed between the tested bacteria. The sensitivity of the multiplex real-time PCR was found to have a lower limit of 10(4) colony-forming units/reaction for all three Vibrio species. The combination strategy raised the isolation ratio of all three Vibrio species 1.26- to 2.75-fold.

CONCLUSION
This assay provides a rapid, sensitive, and specific technique to detect these three Vibrio species in the environment.

Park|Jie Yeun|JY|
Jeon|Semi|S|
Kim|Jun Young|JY|
Park|Misun|M|
Kim|Seonghan|S|

Vibrio cholerae
Vibrio parahaemolyticus
Vibrio vulnificus
TaqMan probe multiplex real-time PCR


Smaller tumor size is associated with poor survival in stage II colon cancer: An analysis of 7,719 patients in the SEER database.

Abstract:
BACKGROUND
We hypothesized that in patients with colon cancer showing heavy intestinal wall invasion without lymph node metastasis (stage II), small tumor size would correlate with more aggressive tumor behaviors and thus poorer cancer-specific survival (CSS).

METHODS
We analyzed Caucasian patients with stage II colon cancer based on data from the US Surveillance, Epidemiology, and End Results (SEER) database. Survival was analyzed using the Kaplan-Meier method, and the log-rank test was used to identify differences. Risk factors were analyzed using the Cox proportional hazard model.

RESULTS
A total of 7719 stage II colon cancer patients from the SEER database were included in the analysis. The cutoff value (5.0 cm) was determined using the X-tile program. The Kaplan-Meier analysis showed that tumors <5.0 cm had a poorer CSS compared to tumors ≥5.0 cm (p = 0.006). Multivariate analysis indicated that tumor size is an independent prognostic factor for stage II patients, and compared to tumors <5.0 cm, tumors ≥5.0 cm were more likely to result in a better CSS (HR 0.775, 95% CI 0.691-0.870, p < 0.001). Tumor size was also analyzed as a continuous variable in the multivariate analysis, and the CSS decreased with decreasing tumor size (HR 0.958, 95% CI 0.936-0.981, p < 0.001). Subgroup analyses suggested that tumor size is also an independent prognostic factor for stage IIA (p = 0.002) and IIC (p < 0.001) patients.

CONCLUSIONS
Smaller tumor size is associated with poor CSS in the stage II colon cancer and particularly in the stage IIA and IIC subgroups.

Huang|Ben|B| Feng|Yang|Y| Zhu|Liang|L| Xu|Tianhong|T| Huang|Liyong|L| Cai|Guoxiang|G|

D000368:Aged
D003110:Colonic Neoplasms
D016208:Databases, Factual
D005260:Female
D006801:Humans
D053208:Kaplan-Meier Estimate
D008297:Male
D008875:Middle Aged
D015999:Multivariate Analysis
D009367:Neoplasm Staging
D011379:Prognosis
D016016:Proportional Hazards Models
D012307:Risk Factors
D018426:SEER Program
D015996:Survival Rate
D047368:Tumor Burden
D014481:United States

Tumor size
Stage II
Colon cancer
Cancer-specific survival


Advances in the management of diabetes: therapies for type 2 diabetes.

Abstract: The incidence of type 2 diabetes is rapidly rising worldwide leading to an increasing burden of cardiovascular and microvascular complications. The aim of treatment of the condition is to improve quality of life and reduce such complications. To this end, improvement in glucose control remains an important consideration. In recent years, important therapeutic advances have occurred in the management of hyperglycaemia in people with type 2 diabetes. These include the use of dipeptidylpeptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists and sodium glucose transporter-2 inhibitors. The latter two classes appear to have some specific beneficial effects on cardiovascular and renal outcomes, independent of their antihyperglycaemic effects. This review aims to outline the current state of diagnosis and management of diabetes for the general physician, with a particular focus on new therapeutic agents for management of glucose in patients with type 2 diabetes.

D000077203:Sodium-Glucose Transporter 2 Inhibitors


Validity of Hepatic or Pancreatic Resection for Elderly Patients Aged 85 Years or Older at a Single Community Hospital in Japan.

Abstract:
AIM
To evaluate the efficacy of age on the surgical outcomes in hepatic or pancreatic resection.

PATIENTS AND METHODS
We performed 50 hepatic or pancreatic resections in our community hospital and divided them into 2 groups based on age: patients aged ≥85 years old and patients aged <85 years old. We calculated the Estimation of Physiologic Ability and Surgical Stress (E-PASS) score and the Physiological and Operative Severity Score for the enumeration of Mortality and Morbidity (POSSUM) system and compared the surgical outcome between the two groups.

RESULTS
There was no significant difference between the two groups with regard to E-PASS and POSSUM scores. Patients aged ≥85 years had a significantly higher frequency of anti-platelet agents. The incidence of postoperative complications and mortality in patients ≥85 years old were comparable to those in patients aged <85 years old.

CONCLUSION
Hepatic or pancreatic resection for elderly patients aged 85 years or older can be safely performed under a given careful patient selection.

Itoh|Shinji|S| Kohnoe|Shunji|S| Shirabe|Ken|K| Yoshida|Daisuke|D| Kawanaka|Hirofumi|H| Yoshizumi|Tomoharu|T| Ikegami|Toru|T| Yamashita|Yo-Ichi|Y| Kurihara|Takeshi|T| Maehara|Yoshihiko|Y|

elderly patient
E-PASS
POSSUM
HPB Surgery


Status of branched endovascular aortic arch repair.

Abstract: Multiple medical device manufacturers are developing branched endografts for thoracic endovascular aortic repair (TEVAR), to provide a minimally invasive alternative for the treatment of aortic arch pathologies in patients who are deemed unfit for open or hybrid arch repair. Different branched endografts have been introduced, with varying number, size and orientation of the branches that redirect flow to the supra-aortic arteries. We present an overview of the currently investigated devices and review their outcomes. The results of branched TEVAR are promising, yet stroke remains the predominant periprocedural concern. For now, these procedures should be limited to select expert centers where the design and deployment procedure of branched endografts can be further developed to reduce the risk of stroke.

van Bakel|Theodorus M|TM|
de Beaufort|Hector W|HW|
Trimarchi|Santi|S|
Marrocco-Trischitta|Massimiliano M|MM|
Bismuth|Jean|J|
Moll|Frans L|FL|
Patel|Himanshu J|HJ|
van Herwaarden|Joost A|JA|

Thoracic endovascular aortic repair (TEVAR)


Application of Solid-State Nanopore in Protein Detection.

Abstract: A protein is a kind of major biomacromolecule of life. Its sequence, structure, and content in organisms contains quite important information for normal or pathological physiological process. However, research of proteomics is facing certain obstacles. Only a few technologies are available for protein analysis, and their application is limited by chemical modification or the need for a large amount of sample. Solid-state nanopore overcomes some shortcomings of the existing technology, and has the ability to detect proteins at a single-molecule level, with its high sensitivity and robustness of device. Many works on detection of protein molecules and discriminating structure have been carried out in recent years. Single-molecule protein sequencing techniques based on solid-state nanopore are also been proposed and developed. Here, we categorize and describe these efforts and progress, as well as discuss their advantages and drawbacks.

Luo|Yuhan|Y| Wu|Linlin|L| Tu|Jing|J|0000-0002-1310-5915 Lu|Zuhong|Z|

solid-state nanopore
protein sequencing
protein conformation
single molecule detection


Hyperhomocysteinemia and Dementia Associated With Severe Cortical Atrophy, but No Amyloid Burden.

Abstract: We report a case of a 77 years old patient who was admitted to our memory clinic because of progressive gait impairment and amnestic cognitive decline associated with extrapyramidal symptoms and behavioral changes. The clinical picture was consistent with a possible diagnosis of Alzheimer's Disease associated with parkinsonian symptoms or with a Parkinson Plus syndrome. After a complete investigation, she was found to have a high plasma level of homocysteine due to homozygous methylene-tetrahydrofolate reductase (MTHFR) gene C665 T polymorphism, cognitive and motor impairment were associated with a severe cortical atrophy and mild subcortical vascular disease. PET neuroimaging excluded a significant amyloid load. Clinically, she showed improvement of the movement disorder and functional status after folate integration plus levodopa and memantine administration. We concluded for a primary degenerative dementia with movement impairment associated with persistent hyperhomocysteinemia. We hypothesized that neurodegeneration is driven by mechanisms linked to homocysteine metabolism possibly associated with tauopathy.

hyperhomocysteinemia
dementia
MTHFR
tauopathy
beta amyloid


The latent structure and predictors of non-medical prescription drug use and prescription drug use disorders: a national study.

Abstract:
BACKGROUND
Despite growing concerns about non-medical prescription drug use and prescription drug use disorders, whether vulnerability for these conditions is drug-specific or occurs through a shared liability and common risk factors is unknown.

METHODS
Exploratory and confirmatory factor analysis of Wave 1 of the National Epidemiologic Survey on Alcohol and Related Conditions were used to examine the latent structure of non-medical prescription drug use and prescription drug use disorders. Multiple Indicators Multiple Causes (MIMIC) analysis was used to examine whether the effect of sociodemographic and psychiatric covariates occurred through the latent factor, directly on each drug class or both.

RESULTS
A one-factor model described well the structure of both non-medical prescription drug use and prescription drug use disorders. Younger age, being White, having more intense pain or one of several psychiatric disorders increased the risk of non-medical prescription drug use through the latent factor. The same covariates, except for anxiety disorders also significantly increased the risk of prescription drug use disorders through the latent factor. Older age directly increased the risk of non-medical use of sedatives, and alcohol use disorders decreased the risk of non-medical tranquilizer use. No covariates had direct effects on the risk of any prescription drug use disorders beyond their effect through the latent factor.

CONCLUSION
The risk for non-medical prescription drug use and prescription drug use disorders occurs through a shared liability. Treatment, prevention and policy approaches directed at these drugs as a group maybe more effective than those focused on individual classes of drugs.

Blanco|Carlos|C|
Rafful|Claudia|C|
Wall|Melanie M|MM|
Jin|Chelsea J|CJ|
Kerridge|Bradley|B|
Schwartz|Robert P|RP|

D000697:Central Nervous System Stimulants

D039721:Diagnostic and Statistical Manual of Mental Disorders

Latent structure
Non-medical prescription drug use
Prescription drug use disorders
NESARC


Transporter effects on cell permeability in drug delivery.

Abstract: The role of drug transporters as one of the determinants of cellular drug permeability has become increasingly evident. Despite the lipophilicity of a drug molecule as rate-limiting factor for passive diffusion across biological membranes, carrier-mediated and active transport have gained attention over the years. A better understanding of the effects and roles of these influx transporters towards transmembrane permeability of a drug molecule need to be delineated for drug development and delivery. Areas covered: This review focuses on findings relative to role of transporters in drug absorption and bioavailability. Particularly the areas demanding further research have been emphasized. This review will also highlight various transporters expressed on vital organs and their effects on drug pharmacokinetics. Expert opinion: Significant efforts have been devoted to understand the role of transporters, their iterative interplay with metabolizing enzymes through molecular enzymology, binding and structure-activity relationship studies. A few assays such as parallel artificial membrane permeation assay (PAMPA) have been developed to analyze drug transport across phospholipid membranes. Although large web-accessible databases on tissue selective expression profiles at transcriptomic as well as proteomic are available, there is a need to collocate the scattered literature on the role of transporters in drug development and delivery.

Mandal|Abhirup|A|
Agrahari|Vibhuti|V|
Khurana|Varun|V|
Pal|Dhananjay|D|
Mitra|Ashim K|AK|

influx
BCRP
BDDCS
MRP
P-gp
Pathways
cancer
efflux
gene
ocular tissues


Low-dose cytokine-induced neutral ceramidase secretion from INS-1 cells via exosomes and its anti-apoptotic effect.

Abstract: It has been reported that the effect of inflammatory cytokines on β-cell destruction in type 1 diabetes is concentration-dependent. However, the underlying mechanisms remain unclear. In the present study, we found that a high concentration of cytokines promoted apoptosis in the rat β-cell line INS-1, whereas a low concentration of cytokines had no effect. We also found that cytokines at a low concentration stimulated neutral ceramidase (NCDase) release via exosomes from INS-1 cells, whereas cytokines at a high concentration inhibited NCDase release. Furthermore, the results showed that the NCDase-containing exosomes isolated from the culture medium of INS-1 cells treated with cytokines at a low concentration inhibited apoptosis induced by a high concentration of cytokines. Finally, the results also showed that the protective action of NCDase in the exosomes on apoptosis was mediated by the generation of sphingosine 1-phosphate (S1P) and its interaction with S1P receptor 2. Taken together, these findings revealed a novel NCDase-S1P-phosphate-S1P receptor 2-dependent mechanism by which a low level of inflammatory cytokines protects pancreatic β-cells from apoptosis induced by a high level of inflammatory cytokines.

Zhu|Qun|Q| Kang|Jian|J| Miao|Heng|H| Feng|Yamin|Y| Xiao|Lijun|L| Hu|Zhigao|Z| Liao|Duan-Fang|DF| Huang|Yan|Y| Jin|Junfei|J| He|Songqing|S|

neutral ceramidase
exosome
cytokine
β-cell
apoptosis


Patterns of interrelation between perception and understanding of images and texts with different degree of blur.

Abstract: The efficiency of information processing depends on a holistic and integrated process of understanding. Eye tracking helps us to study the peculiarities of the understanding of visually perceived stimuli. The purpose of this study was to identify and characterize the relationship between perception and understanding, on the example of images and texts with different degrees of blurring (visual complexity). The work involved 25 participants, ages 19 to 25 years. Methods include poll, recording eye movements (eye tracking), wavelet filtering of text and images, and content analysis. Stimuli were consistently presented on the screen included text stimuli (from 7 texts), episodes from Russian fairy tales, and images (from 8 comics total), each consisting of eight pictures, united by one complete plot. Visual stimuli were presented in order from the clearest to the most blurred image. The results of the study showed that the participants made more gaze fixations on plot-relevant details and characters. They reveal key details of images for a general understanding of the content. The willful regulation of cognitive processes allows distinguishing the main characters and keywords to recreate or anticipate the meaning of visually perceived information constructs while reading texts or pictures with a high degree of blur.

Eye tracking
Content analysis
Cognitive processes
Content understanding
Visual perception


Corneal Hydrops Secondary to Intrastromal Corneal Ring Intrusion into the Anterior Chamber 7 Years after Implantation: A Case Report.

Abstract:
INTRODUCTION
This report describes the first known case of late-onset intrusion of an intrastromal ring segment into the anterior chamber due to posterior migration of a ring segment. To our knowledge, intrastromal ring segment penetration has only been shown to occur in the intraoperative or immediate postoperative period. We postulate that the perforation in this case is due to progressive thinning of the cornea, possibly in combination with habitual eye rubbing.

CASE REPORT
A 44-year-old man presented with acute corneal hydrops related to penetration of Descemet's membrane and endothelium by an intrastromal ring segment implanted 7 years prior. Removal of the ring segment resulted in an anterior chamber fistula that directed fluid through the ring segment tunnel to the ocular surface. Leakage of aqueous humor was successfully controlled, and corneal edema gradually resolved.

CONCLUSION
This case indicates the need for long term monitoring of ring segment proximity to the posterior corneal surface, especially in patients with ectatic ocular conditions and/or habitual eye rubbing behavior.

Moshirfar|Majid|M|
Bean|Andrew E|AE|
Desautels|Jordan D|JD|
Birdsong|Orry C|OC|

Corneal hydrops
Intrastromal corneal ring
Corneal edema
Corneal thinning
Descemet’s rupture
Ectasia
INTACS
Keratoconus
LASIK


Hyperuricemia and chronic kidney disease: an enigma yet to be solved.

Abstract: The role of uric acid (UA) on the pathogenesis and progression of chronic kidney disease (CKD) remains controversial. Experimental and clinical studies indicate that UA is associated with several risk factors of CKD including diabetes, hypertension, oxidative stress, and inflammation and hyperuricemia could be considered as a common dominator linking CKD and cardiovascular disease. Notably, the impact of serum UA levels on the survival of CKD, dialysis patients, and renal transplant recipients is also a matter of debate, as there are conflicting results from clinical studies. At present, there is no definite data whether UA is causal, compensatory, coincidental or it is only an epiphenomenon in these patients. In this article, we attempt to review and elucidate the dark side of this old molecule in CKD and renal transplantation.

Dousdampanis|Periklis|P|
Trigka|Konstantina|K|
Musso|Carlos G|CG|
Fourtounas|Costas|C|

hyperuricemia
Chronic kidney disease
dialysis
renal transplantation
mortality


Simple 3-criteria-based ex vivo confocal diagnosis of basal cell carcinoma.

Abstract:
BACKGROUND
Fast and simple microscopic evaluation of basal cell carcinoma (BCC) together with its subtype determination would accelerate diagnostic and therapeutic procedures in dermatology including Mohs surgery.

OBJECTIVES
Assessing whether simplified 3-criteria-based ex vivo confocal microscopic (CM) examination can reliably predict BCC diagnosis and subtype. Analyzing interobserver agreement between expert and novice examiner.

METHODS
CM images of 235 skin samples from 150 patients were prospectively evaluated by 2 blinded examiners for the presence of 3 predefined BCC criteria namely presence of tumor mass, peripheral palisading and clefting.

RESULTS
Out of 235 skin samples 116 showed histological presence of BCC, confocally expert diagnosed a BCC in 110 and novice examiner in 107 samples. The overall sensitivity and specificity of detecting residual BCC was 96.6% and 98.7%, respectively. Confocally, examiners diagnosed correctly nodular BCC in 96.6%, respectively, 98.3%, superficial BCC in 96.8%, respectively, 93.5%, infiltrating BCC in 88.9%, respectively, 83.3% and other BCC subtype in 22.2%, respectively, 0% (expert and novice examiner, respectively).

CONCLUSION
Ex vivo CM allowed intraoperative examination of BCC based on only 3-criteria with high sensitivity and specificity, provided useful information on tumor subtype and showed that both experienced and non-experienced examiners may use this diagnostic approach with excellent results.

Hartmann|Daniela|D|0000-0002-1002-8133
Krammer|Sebastian|S|
Bachmann|Mario R|MR|
Mathemeier|Leonie|L|
Ruzicka|Thomas|T|
von Braunmühl|Tanja|T|

Mohs surgery
diagnostics in dermatology
fluorescence confocal microscopy
infiltrating basal cell carcinoma
nodular basal cell carcinoma
rapid pathology
skin surgery
skin tumors
superficial basal cell carcinoma


An Evidence-based Approach toward a Sustainable Healthcare System.

Abstract: Japan is the most rapidly aging country in the world, and the sustainability of its health and social care system is a top priority. In order to have a sustainable healthcare system, global protection of healthcare commons through regulations, together with a market mechanism based on societal values, is critical. An evidence-based approach is needed to attain that; however, the current methodologies for this approach have major limitations, such as the lack of common healthcare goals, the retrospective nature of evidence, and the uncertainty and ambiguity of the available data. This opinion paper discusses the challenges in developing a sustainable system and proposes a feasible way to overcome the limitations.

sustainability
evidence-based health policy
health system
population aging


Speech-aid prosthesis in velopharyngeal incompetency patient with cleft palate: can speech aids be applicable for adult patient?

Abstract:
BACKGROUND
Velopharyngeal incompetence (VPI) therapy for cleft palate (speech therapy alone, speech therapy using speech aids, or combined therapy such as speech therapy using a pharyngeal flap), is more effective in younger patients than in adult patients. Speech therapy is known as very difficult for patients who still have VPI as an adult. Because of the possibility of subsequent speech disorders, the timing of surgery for cleft palate is accelerating. Herein, we present a case of an adult with articulation disorder due to VPI who was treated by speech therapy and a speech-aid prosthesis.

CASE PRESENTATION
A woman who underwent cleft palate surgery at 8 years of age still had difficulty with articulation due to VPI as a 24-year-old adult because of a lack of continuous speech therapy. We decided to use a speech-aid application using palatal lift, and a reduction program was conducted four times, along with simultaneous speech therapy, over a period of 1 year and 7 months. During the therapy period, she was able to speak normally within a relatively short period of time, and after implementation of the reduction program, the therapy was completed by completely removing the device. Long-term observations have shown normal speech function without recurrence, even after the device was removed.

CONCLUSION
As seen in this case, speech therapy using speech aids can show a good result for adult patients with cleft palate who missed the usual timing for the treatment of articulation disorders, depending on the situation. Therefore, it is hereby reported as a therapy option worthy of consideration.


Children's classification and lexicalization of attractiveness, gender, and race: differential displays of these concepts and relatedness to bias and flexibility.

Abstract: Minimal research has examined children's functional use of attractiveness to classify and label others, an important step in the development of children's biases. This study compared 3- to 11-year-olds' classification, sorting, and labeling of others and themselves based on attractiveness, gender, and race and also investigated whether these abilities and other characteristics predicted children's bias and flexibility. Relative to gender and race, children rarely used attractiveness to spontaneously classify people and were less accurate at sorting and labeling others and themselves by attractiveness, suggesting that they have a less explicit concept of attractiveness. Predictors of bias differed depending on domain and assessment method (forced choice or non-forced choice), showing that children's bias is affected by both individual differences and task characteristics. Predictors of flexibility differed based on whether children were assigning positive or negative traits to target children, demonstrating that the valence of attributes is an important consideration when conceptualizing children's flexibility.

Rennels|Jennifer L|JL|
Langlois|Judith H|JH|

Classification Attractiveness Gender Race Bias Flexibility


Metagenomic analysis exploring taxonomic and functional diversity of soil microbial communities in Chilean vineyards and surrounding native forests.

Abstract: Mediterranean biomes are biodiversity hotspots, and vineyards are important components of the Mediterranean landscape. Over the last few decades, the amount of land occupied by vineyards has augmented rapidly, thereby increasing threats to Mediterranean ecosystems. Land use change and agricultural management have important effects on soil biodiversity, because they change the physical and chemical properties of soil. These changes may also have consequences on wine production considering that soil is a key component of terroir. Here, we describe the taxonomic diversity and metabolic functions of bacterial and fungal communities present in forest and vineyard soils in Chile. To accomplish this goal, we collected soil samples from organic vineyards in central Chile and employed a shotgun metagenomic approach to sequence the microbial DNA. Additionally, we studied the surrounding native forest to obtain a baseline of the soil conditions in the area prior to the establishment of the vineyard. Our metagenomic analyses revealed that both habitats shared most of the soil microbial species. The most abundant genera in the two habitats were the bacteria Candidatus Solibacter and Bradyrhizobium and the fungus Gibberella. Our results suggest that the soil microbial communities are similar in these forests and vineyards. Therefore, we hypothesize that native forests surrounding the vineyards may be acting as a microbial reservoir buffering the effects of the land conversion. Regarding the metabolic diversity, we found that genes pertaining to the metabolism of amino acids, fatty acids, and nucleotides as well as genes involved in secondary metabolism were enriched in forest soils. On the other hand, genes related to miscellaneous functions were more abundant in vineyard soils. These results suggest that the metabolic function of microbes found in these habitats differs, though differences are not related to taxonomy. Finally, we propose that the implementation of environmentally friendly practices by the wine industry may help to maintain the microbial diversity and ecosystem functions associated with natural habitats.

Wine
Bacterial diversity
Conservation
Ecosystem services
Fungal diversity
Pyrosequencing
Shotgun sequencing


One Year of SARS-CoV-2: How Much Has the Virus Changed?

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide crisis with profound effects on both public health and the economy. In order to combat the COVID-19 pandemic, research groups have shared viral genome sequence data through the Global Initiative on Sharing All Influenza Data (GISAID). Over the past year, ≈290,000 full SARS-CoV-2 proteome sequences have been deposited in the GISAID. Here, we used these sequences to assess the rate of nonsynonymous mutants over the entire viral proteome. Our analysis shows that SARS-CoV-2 proteins are mutating at substantially different rates, with most of the viral proteins exhibiting little mutational variability. As anticipated, our calculations capture previously reported mutations that arose in the first months of the pandemic, such as D614G (Spike), P323L (NSP12), and R203K/G204R (Nucleocapsid), but they also identify more recent mutations, such as A222V and L18F (Spike) and A220V (Nucleocapsid), among others. Our comprehensive temporal and geographical analyses show two distinct periods with different proteome mutation rates: December 2019 to July 2020 and August to December 2020. Notably, some mutation rates differ by geography, primarily during the latter half of 2020 in Europe. Furthermore, our structure-based molecular analysis provides an exhaustive assessment of SARS-CoV-2 mutation rates in the context of the current set of 3D structures available for SARS-CoV-2 proteins. This emerging sequence-to-structure insight is beginning to illuminate the site-specific mutational (in)tolerance of SARS-CoV-2 proteins as the virus continues to spread around the globe.

SARS-CoV-2
COVID-19
sequence
proteome
mutations
3D proteins


Reexamining the risks of drinking-water nitrates on public health.

Abstract:
BACKGROUND
Nitrates in drinking water are generally considered the sole source of nitrite poisoning with methemoglobinemia in infantile methomoglobinemia (IM). However, IM, which occurs during the first 4 months of life, is actually a constellation of cyanosis and hypoxia associated with methemoglobinemia that can result from several other causes.

METHODS
This review reexamines the role of nitrate levels in drinking water as a cause of IM and identifies other sources of nitrates that can affect public health and cause chronic diseases.

RESULTS
Causes of IM include nitrites in foods, environmental chemical exposures, commonly prescribed pharmaceuticals, and the endogenous generation of oxides of nitrogen. Infants with congenital enzyme deficiencies in glucose-6-phosphate dehydrogenase and methemoglobin reductase are at greater risk of nitrite-induced methemoglobinemia from nitrates in water and food and from exposures to hemoglobin oxidizers.

CONCLUSION
Early epidemiological studies demonstrated significant associations between high groundwater nitrate levels and elevated methemoglobin levels in infants fed drinking water-diluted formulas. However, more recent epidemiological investigations suggest other sources of nitrogenous substance exposures in infants, including protein-based formulas and foods and the production of nitrate precursors (nitric acid) by bacterial action in the infant gut in response to inflammation and infection.

Richard|Alyce M|AM|
Diaz|James H|JH|
Kaye|Alan David|AD|


Treatment Strategies for Pilonidal Sinus Disease in Switzerland and Austria.

Abstract: Background and objective: No current nationwide consensus exists on pilonidal disease (PD) treatment in Switzerland and Austria. The objective of this study was to assess and compare the spectrum of PD treatment strategies in Switzerland and Austria. Materials and Methods: A survey including 196 certified institutions (Switzerland, N = 99 and Austria, N = 97) was performed. Treatment strategies for both chronic and acute pilonidal disease were investigated, as well as evolution of treatment over the last 20 years. Results: In total, 92 of 196 (47%) hospitals participated in the survey. Recurrence rate (20%) was similar between the two countries. In acute pilonidal disease, a two-stage approach with incision and drainage as the first step was preferred over a one-stage procedure in both countries. In Austria, all patients with chronic pilonidal disease were treated as inpatients, whereas 28% of patients in Switzerland were treated on an outpatient basis (p = 0.0019). Median length of hospital stay was double in Austria (four days) compared to Switzerland (two days; p < 0.001). Primary resection and off-midline closure (p = 0.017) and the use of tissue flaps (p = 0.023) were performed more commonly in Austria than in Switzerland. Minimally invasive techniques were performed more often in Switzerland than in Austria (52% vs. 4%, p < 0.001). Overall, wide excision with secondary wound healing or midline closures declined over the last 20 years. Conclusion: Treatment strategies for chronic PD differ between Austria and Switzerland with more and longer inpatient care in Austria, increasingly minimally invasive approaches in Switzerland, and outdated procedures still being performed in both countries. Overall, heterogeneity of practice dominates in both countries.

Switzerland
Austria
pilonidal disease
survey


Association of ABCB1 polymorphisms with lipid homeostasis and liver injury response to atorvastatin in the Chinese population.

Abstract: The present research was to assess the relationship between ABCB1 (G2677T/A, C3435T) polymorphisms and lipid homeostasis as well as risk of liver injury induced by atorvastatin in in-patients from China. The lipid levels (total cholesterol, high-density lipoprotein, triglycerides) as well as metabolic enzymes of hepar (glutamic-pyruvic transaminase, glutamic-oxalacetic transaminase, alkaline phosphatase, γ-glutamyl transpeptidase) in plasma for 162 patients were measured at baseline and after approximately 6 months of atorvastatin treatment. Polymorphisms of the ABCB1 gene were determined using the Snapshot technique. The associations between genetic polymorphisms and lipid levels as well as hepar indexes were evaluated at the end of medical treatment. Based on one-way ANOVA analysis, patients with the 2677GG or 3435TT genotypes showed a remarkable decrease in percentage when the level of TC was above 4.00 mmol·L-1, separately (P < 0.05). There was a significant decrease in percentage in the frequency of patients with the 2677GG genotype (low-density lipoprotein > 2.00 mmol·L-1) (P < 0.05). The level of glutamic-pyruvic transaminase in patients with the 2677GG or 3435CC genotype displayed a significantly increase in percentage, respectively (P < 0.05). The ABCB1 G-C haplotype carriers were associated with an increased risk of AILI. The results provide evidence for clinically individualised utilisation of atorvastatin for lipid homeostasis as well as risk of induced liver injury in the Chinese population.

Qu|Kan-Kan|KK| Zhang|Chen-Ning|CN| Dong|Li-Xia|LX| Wang|Shu-Shan|SS| Zhang|Zhong-Dong|ZD| Zhang|Lin|L|

D018435:ATP Binding Cassette Transporter, Subfamily B

ABCB1 polymorphisms
lipid homeostasis
atorvastatin
atorvastatin
Chinese population
risk of liver injury
atorvastatine
homéostasie des lipids
polymorphismes du gène ABCB1
population chinoise
risque de lésions hépatiques


Colorimetric and energy transfer based fluorometric turn-on method for determination of microRNA using silver nanoclusters and gold nanoparticles.

Abstract: The authors describe a dual (colorimetric and fluorometric) detection scheme for microRNA. The method is based on the use of fluorescent DNA-modified silver nanoclusters (DNA-AgNCs) and gold nanoparticles (AuNPs). The DNA-AgNCs were linked to AuNPs via the interaction of ssDNA-AgNC probes with AuNPs. This led to quenching of the fluorescence of the DNA-AgNCs (best measured at excitation/emission peaks of 370/450 nm) and also prevents salt-induced aggregation of the AuNPs. Upon addition of microRNA, the DNA on the AgNCs hybridizes with microRNA. This led to the formation of a DNA-AgNC/miRNA hetero-duplex and increase of the distance to the AuNPs. Quenching was suppressed and fluorescence was restored. The presence of microRNA also affected salt-induced particle aggregation as reflected by a color change from red to purple that is visible with bare eyes. The visual detection limit for microRNA is 0.6 nM, and the fluorometric detection limit is 0.4 pM. Graphical abstract Schematic of the colorimetric and fluorometric assay for microRNA (miRNA). It is based on the use of fluorescent DNA-modified silver nanoclusters (AgNCs) and gold nanoparticles (AuNPs).

Borghei|Yasaman-Sadat|YS|
Hosseini|Morteza|M|0000-0002-1492-7443
Ganjali|Mohammad Reza|MR|
Ju|Huangxian|H|

Energy transfer
microRNA
Colorimetric analysis
Deaggregation
Fluorescent biosensing


Intron-mediated regulation of β-tubulin genes expression affects the sensitivity to carbendazim in Fusarium graminearum.

Abstract: The plant pathogenic fungus, Fusarium graminearum, is known to have two β-tubulin genes (named Fg-β1tub and Fg-β2tub). Mutations in Fg-β2tub rather than in Fg-β1tub have been shown to confer resistance to carbendazim (MBC), even though Fg-β1tub has higher homology than Fg-β2tub to the β-tubulin isotypes related to benzimidazole resistance in other fungi. However, sequence alignment of β-tubulin isotypes related to benzimidazole resistance showed that the number and position of introns in Fg-β2tub are more consistent than Fg-β1tub to those in other β-tubulin genes. In detail, Fg-β1tub lacks three introns, i.e., intron i3, i4, and i6 corresponding to positions in Fg-β2tub of F. graminearum. To investigate the effects of the divergence introns on the function of β-tubulins in F. graminearum, a strategy of intron deletion and insertion was used. Our results showed that deletion of the second intron from Fg-β1tub gene increased Fg-β1tub expression levels leading to increased sensitivity to MBC. Besides, inserting the divergence introns into Fg-β1tub can increase Fg-β1tub expression leading to increased sensitivity to MBC. In addition, intron-mediated Fg-β1tub gene expression requires a splicing-competent intron within the body of the host gene. Furthermore, the insertion and deletion of introns in Fg-β1tub gene have no significant effect on hyphal growth, conidiation and virulence in F. graminearum. Thus, we proposed that introns may be among the factors contributing to the evolution and functional divergence of two β-tubulin genes and also significantly regulate the expression of β-tubulin genes, which, in turn, affects sensitivity to MBC fungicides in F. graminearum.

Li|Yanjun|Y| Chen|Dongming|D| Luo|Shunwen|S| Zhu|Yuanye|Y| Jia|Xiaojing|X| Duan|Yabing|Y| Zhou|Mingguo|M|

D015966:Gene Expression Regulation, Fungal

β-tubulin
Gene expression
Fusarium graminearum
Intron
Evolution
Fungicide sensitivity


Local tissue effects of various barrier membranes in a rat subcutaneous model.

Abstract:
PURPOSE
The purpose of this study was to examine the local tissue reactions associated with 3 different poly(lactic-co-glycolic acid) (PLGA) prototype membranes and to compare them to the reactions associated with commercially available resorbable membranes in rats.

METHODS
Seven different membranes-3 synthetic PLGA prototypes (T1, T2, and T3) and 4 commercially available membranes (a PLGA membrane, a poly[lactic acid] membrane, a native collagen membrane, and a cross-linked collagen membrane)-were randomly inserted into 6 unconnected subcutaneous pouches in the backs of 42 rats. The animals were sacrificed at 4, 13, and 26 weeks. Descriptive histologic and histomorphometric assessments were performed to evaluate membrane degradation, visibility, tissue integration, tissue ingrowth, neovascularization, encapsulation, and inflammation. Means and standard deviations were calculated.

RESULTS
The histological analysis revealed complete integration and tissue ingrowth of PLGA prototype T1 at 26 weeks. In contrast, the T2 and T3 prototypes displayed slight to moderate integration and tissue ingrowth regardless of time point. The degradation patterns of the 3 synthetic prototypes were similar at 4 and 13 weeks, but differed at 26 weeks. T1 showed marked degradation at 26 weeks, whereas T2 and T3 displayed moderate degradation. Inflammatory cells were present in all 3 prototype membranes at all time points, and these membranes did not meaningfully differ from commercially available membranes with regard to the extent of inflammatory cell infiltration.

CONCLUSIONS
The 3 PLGA prototypes, particularly T1, induced favorable tissue integration, exhibited a similar degradation rate to native collagen membranes, and elicited a similar inflammatory response to commercially available non-cross-linked resorbable membranes. The intensity of inflammation associated with degradable dental membranes appears to relate to their degradation kinetics, irrespective of their material composition.

Polylactic acid-polyglycolic acid copolymer


Prevalence of Anaplasma phagocytophilum in humans in Belgium for the period 2013-2016.

Abstract: Ticks are vectors for a broad range of pathogens of medical and veterinary importance, such as Borrelia spp., Babesia spp., Anaplasma spp., Rickettsia spp., Bartonella spp. and the tick-borne encephalitis virus. The Gram-negative bacterium Anaplasma phagocytophilum is present worldwide, including Belgium where numerous patients were shown to harbour antibodies against this pathogen as recorded by the Belgian National Reference Center (NRC) for Anaplasma. The clinical presentation of human granulocytic anaplasmosis is an acute, febrile, nonspecific, flu-like illness. Leukopenia, thrombocytopenia and increased hepatic transaminase activities are commonly present early in the disease. Diagnosis early in the course of infection relies on the detection of antibodies or of the bacterium in the blood, as is performed at the NRC for Anaplasma, part of the Clinical Laboratory of the Queen Astrid Military Hospital in Brussels, Belgium. In this article, we discuss diagnostic test results as well as recent clinical and demographic characteristics of patients whose samples were analyzed by the NRC for Anaplasma in a four-year period (2013-2016).

Anaplasma phagocytophilum
human granulocytic anaplasmosis
diagnostic testing
clinical management


Patients' experiences of lifestyle discussions based on motivational interviewing: a qualitative study.

Abstract:
BACKGROUND
According to World Health Organization about 75% of cardiovascular diseases and type 2 diabetes and 40% of all cases of cancer could be prevented if the risk factors tobacco use, unhealthy diets, physical inactivity and harmful use of alcohol could be eliminated. Patients often need help in monitoring themselves to make the proper lifestyle changes and it is important that adequate support is provided to enable the patients to take control over their health. Motivational interviewing is a framework that can help to facilitate this movement. The aim of this study was to describe how patients in primary health care settings experience lifestyle discussions based on motivational interviewing.

METHODS
This study has a descriptive design and qualitative content analysis was used as the method. Sixteen patients who had each visited a registered nurse for lifestyle discussions were interviewed.

RESULTS
The results show that the lifestyle discussions could enable self-determination in the process of lifestyle change but that certain conditions were required. Mutual interaction between the patient and the nurse that contributes to a sense of well-being in the patients was a necessary condition for the lifestyle discussion to be helpful. When the discussion resulted in a new way of thinking about lifestyle and when patient initiative was encouraged, the discussion could contribute to change. The patient's free will to make a lifestyle change and the nurse's sensitivity in the discussions created fertile soil for change.

CONCLUSIONS
This study focuses on MI-based discussions, and the result shows that a subset of patients, who self-reported that they are motivated and aware of their role in making lifestyle changes, appreciate these strategies. However, it is not known whether discussions would be experienced in the same way if RNs used another method or if patients who were less motivated, engaged, or aware of their role in making lifestyle changes were interviewed.

Brobeck|Elisabeth|E| Odencrants|Sigrid|S| Bergh|Håkan|H| Hildingh|Cathrine|C|

Lifestyle discussion
Motivational interviewing
Primary health care
Content analysis
Nurse
Patient experiences


Development of a targeted method for twenty-three metabolites related to polyphenol gut microbial metabolism in biological samples, using SPE and UHPLC-ESI-MS/MS.

Abstract: An increasing number of studies have concerned the profiling of polyphenol microbial metabolites, especially in urine or plasma, but only a few have regarded their accurate quantification. This study reports on a new ultra-performance liquid chromatography tandem mass spectrometry method with electrospray ionisation (UHPLC-ESI-MS/MS) using a simple clean-up step with solid phase extraction (SPE) and validation on different biological matrices. The method was tested with spiked samples of liver, heart, kidneys, brain, blood and urine. The purification procedure, after the evaluation of three different cartridges, makes it possible to obtain cleaner samples and better quantification of putative trace metabolites, especially related to dietary studies, with concentrations below ng/g in tissue and for urine and blood, starting from ng/ml. Limits of detection and linear range were also assessed using mixed polyphenol metabolite standards. Short chromatographic separation was carried out for 23 target compounds related to the polyphenol microbial metabolism, coupled with a triple quadrupole mass spectrometer for their accurate quantification. By analysing different spiked biological samples we were able to test metabolite detection in the matrix and validate the overall recovery of the method, from purification to quantification. The method developed can be successfully applied and is suitable for high-throughput targeted metabolomics analysis related to nutritional intervention, or the study of the metabolic mechanism in response to a polyphenol-rich diet.

Gasperotti|Mattia|M| Masuero|Domenico|D| Guella|Graziano|G| Mattivi|Fulvio|F| Vrhovsek|Urska|U|

D002851:Chromatography, High Pressure Liquid

D021241:Spectrometry, Mass, Electrospray Ionization

Polyphenol
Targeted metabolomics
Fruit consumption
Gut microbiota
MRM


Effects of aging and exercise training on apoptosis in the heart.

Abstract: Aging is characterized by a progressive decline in cardiac function. A critical contributor to the age-related impairment in cardiac function is the loss of cardiac myocytes through "apoptosis", or programmed cell death. Structural remodeling in the heart with advancing age includes (a) loss of cardiomyocytes, (b) reactive hypertrophy of the remaining cardiomyocytes, and (c) increased connective tissue and altered geometry. The loss of cardiomyocytes with aging occurs through apoptosis. Particularly, mitochondrial-mediated apoptotic pathway is the best characterized and believed critical in regulating apoptosis with aging, suggesting that mitochondria are very important sites of programmed cell death. It has been also reported that mitochondrial dysfunction, oxidative stress, and impaired stress response contribute to age-induced mechanical remodeling as well as apoptosis. In contrast, exercise training not only improves cardiac function, but also reduces the risk of heart disease. We recently found that aging increased mitochondrial-mediated apoptotic signaling and apoptosis in the left ventricle, while chronic exercise training was effective in diminishing mitochondrial-mediated apoptotic signaling pathways in the aging heart, as indicated by lower DNA fragmentation, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive staining, and caspase-3 cleavage, when compared with left ventricles from the age-matched sedentary group. In this review, we will provide a comprehensive update regarding the effects of aging and exercise training on apoptosis in the heart.

Aging Apoptosis Heart Myocytes Mitochondria


DNA helicase RecQ1 regulates mutually exclusive expression of virulence genes in Plasmodium falciparum via heterochromatin alteration.

Abstract: The Plasmodium falciparum var gene family encodes ∼60 surface antigens by which parasites escape the host immune responses via clonal expression of var genes. However, the mechanism controlling this mutual exclusivity, associated with alterations in chromatin assembly, is not understood. Here, we determined how expression of the var gene family is regulated by two RecQ DNA helicase family members, PfRecQ1 and PfWRN, in P. falciparum Through genetic manipulation, we found that the complete var repertoire was silenced on PfRecQ1 knockout, whereas their expression did not show noticeable changes when PfWRN was knocked out. More important, mutually exclusive expression of var genes could be rescued by complementation of PfRecQ1. In addition, knocking out either of these two helicase genes changed the perinuclear cluster distribution of subtelomeres and subtelomeric var genes. Whereas deletion of PfRecQ1 increased the heterochromatin mark trimethylated (H3K9me3) at the transcription start site (TSS) of the var gene upsC1, that deletion had no effect on the global distribution of H3K9me3 over gene bodies, including those for the var genes. ChIP-seq assay showed that PfRecQ1 was enriched globally at the TSSs of all genes, whereas PfWRN-enriched regions occurred at the gene bodies of the var gene family, but not of other genes or at TSSs of all genes. On PfRecQ1 deletion, the upsC1 var gene moved from the active perinuclear transcription region to a silenced region of the upsC type. These findings imply that PfRecQ1, but not PfWRN, is essential for maintaining the clonal expression of var genes.

Li|Zhou|Z| Yin|Shigang|S| Sun|Maoxin|M| Cheng|Xiu|X| Wei|Jieqiong|J| Gilbert|Nicolas|N| Miao|Jun|J| Cui|Liwang|L| Huang|Zhenghui|Z| Dai|Xueyu|X| Jiang|Lubin|L|

D042002:Chromatin Assembly and Disassembly

DNA helicases
mutually exclusive expression
virulence gene
Plasmodium falciparum
heterochromatin


Oxidative stress and tardive dyskinesia: pharmacogenetic evidence.

Abstract: Tardive dyskinesia (TD) is a serious adverse effect of long-term antipsychotic use. Because of genetic susceptibility for developing TD and because it is difficult to predict and prevent its development prior to or during the early stages of medication, pharmacogenetic research of TD is important. Additionally, these studies enhance our knowledge of the genetic mechanisms underlying abnormal dyskinetic movements, such as Parkinson's disease. However, the pathophysiology of TD remains unclear. The oxidative stress hypothesis of TD is one of the possible pathophysiologic models for TD. Preclinical and clinical studies of the oxidative stress hypothesis of TD indicate that neurotoxic free radical production is likely a consequence of antipsychotic medication and is related to the occurrence of TD. Several studies on TD have focused on examining the genes involved in oxidative stress. Among them, manganese superoxide dismutase gene Ala-9Val polymorphisms show a relatively consistent association with TD susceptibility, although not all studies support this. Numerous pharmacogenetic studies have found a positive relationship between TD and oxidative stress based on genes involved in the antioxidant defense mechanism, dopamine turnover and metabolism, and other antioxidants such as estrogen and melatonin. However, many of the positive findings have not been replicated. We expect that more research will be needed to address these issues.

Oxidative stress
Tardive dyskinesia
Tardive dyskinesia
Pharmacogenetics
TD
Parkinson's disease
manganese superoxide dismutase
superoxide dismutase
AIMS
ATP
Abnormal Involuntary Movement Scale
CAT
CYP
FGAs
GABA
GSH-Px
GSTs
H(2)O(2)
LID
MAO
MnSOD
NAD(P)H quinone oxidoreductase
NOS
NQO
O(2)(−)
PD
ROS
SGAs
SNP
SOD
UCP
adenosine triphosphate
catalase
cytochrome P450
first-generation antipsychotics
glutathione S-transferases
glutathione peroxidase
hydrogen peroxide
l-3,4-dihydroxyphenylalanine
l-DOPA
l-DOPA-induced dyskinesia
monoamine oxidase
nitric oxide synthase
reactive oxygen species
second-generation antipsychotics
single nucleotide polymorphism
superoxide anion
tardive dyskinesia
uncoupling protein
γ-aminobutyric acid

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


Is experienced pregnancy in women with repaired tetralogy of Fallot related to diffuse myocardial fibrosis?

Abstract:
OBJECTIVES
To assess the impact of pregnancy on cardiac function and fibrosis by cardiovascular magnetic resonance (CMR) in patients with repaired Tetralogy of Fallot (rToF).

BACKGROUND
CMR T1 mapping can assess diffuse myocardial fibrosis which is associated to adverse clinical outcomes. Right ventricular (RV) accelerated remodeling is reported in rToF women with experienced pregnancy.

METHODS
We included rToF women from the national registry of congenital heart disease to perform CMR, assessing functional data, T1 mapping/ extracellular volume fraction (ECV). The results including clinical data were compared between women with experienced pregnancy vs non-experienced pregnancy and healthy individuals.

RESULTS
Fifty rToF women performed CMR, median age 36 (range 21-67) years. Fifteen were nulliparous. T1 mapping was compared to 30 controls, (14 women) median age 42 (24-64) years. In the left ventricle (LV), T1 times and ECV in all rToF women vs female controls were 1248 ± 61 ms/ 25.8 ± 2.9% vs 1255 ± 40 ms/ 26.8 ± 3.1%, p = 0.7 and p = 0.3, respectively. In rToF, RV T1 times was 1385 ± 124 ms and ECV 37.7 ± 5.4%. There was no association to parity or age in rToF LV T1/ ECV, p = 0.9 for both, or RV T1/ECV, p = 0.4 and p = 0.6, respectively. Indexed LV mass was higher in the rToF pregnancy group, 43 ± 10 vs 38 ± 6 g/m2, p = 0.03 while RV ejection fraction was lower, 49 ± 7% vs 53 ± 6%, p = 0.04.

CONCLUSION
Women with rTOF showed evidence of increased RV CMR markers suggestive of diffuse fibrosis while LV CMR markers were within normal values. Having experienced pregnancy might affect RV function, however without association to CMR biomarkers.

de Lange|Charlotte|C|
Quattrone|Alessia|A|
Try|Kirsti|K|
Bakke|Anita Helset|AH|
Borger Kvaslerud|Anette|A|
Haugaa|Kristina|K|
Estensen|Mette-Elise|ME|

D019028:Magnetic Resonance Imaging, Cine

Pregnancy
Tetralogy of Fallot
MR T1 mapping
Magnetic resonance imaging


In Vivo Myoblasts Tracking Using the Sodium Iodide Symporter Gene Expression in Dogs.

Abstract: Stem cell-based therapies are a promising approach for the treatment of degenerative muscular diseases; however, clinical trials have shown inconclusive and even disappointing results so far. Noninvasive cell monitoring by medicine imaging could improve the understanding of the survival and biodistribution of cells following injection. In this study, we assessed the canine sodium iodide symporter (cNIS) reporter gene as an imaging tool to track by single-photon emission computed tomography (SPECT/CT) transduced canine myoblasts after intramuscular (IM) administrations in dogs. cNIS-expressing cells kept their myogenic capacities and showed strong 99 mTc-pertechnetate (99 mTcO4 -) uptake efficiency both in vitro and in vivo. cNIS expression allowed visualization of cells by SPECT/CT along time: 4 h, 48 h, 7 days, and 30 days after IM injection; biopsies collected 30 days post administration showed myofiber's membranes expressing cNIS. This study demonstrates that NIS can be used as a reporter to track cells in vivo in the skeletal muscle of large animals. Our results set a proof of concept of the benefits NIS-tracking tool may bring to the already challenging cell-based therapies arena in myopathies and pave the way to a more efficient translation to the clinical setting from more accurate pre-clinical results.

Punzón|Isabel|I|
Mauduit|David|D|
Holvoet|Bryan|B|
Thibaud|Jean-Laurent|JL|
de Fornel|Pauline|P|
Deroose|Christophe M|CM|
Blanchard-Gutton|Nicolas|N|
Vilquin|Jean-Thomas|JT|
Sampaolesi|Maurilio|M|
Barthélémy|Inès|I|
Blot|Stéphane|S|

sodium iodide symporter
dog
SPECT/CT
GRMD
cell therapy
in vivo imaging
myoblast transplantation


Robot-assisted urologic surgery in 2010 - Advancements and future outlook.

Abstract: Robotic surgery is a cutting edge and minimally invasive procedure, which has generated a great deal of excitement in the urologic community. While there has been much advancement in this emerging technology, it is safe to say that robotic urologic surgery holds tremendous potential for progress in the near future. Hence, it is paramount that urologists stay up-to-date regarding new developments in the realm of robotics with respect to novel applications, limitations and opportunities for incorporation into their practice. Robot-assisted surgery provides an enhanced 3D view, increased magnification of the surgical field, better manual dexterity, relatively bloodless field, elimination of surgeon's tremor, reduction in a surgeon's fatigue and mitigation of scattered light. All these factors translate into greater precision of surgical dissection, which is imperative in providing better intraoperative and postoperative outcomes. Pioneering work assessing the feasibility of robotic surgery in urology began in the early 2000's with robot-assisted radical prostatectomy and has since expanded to procedures such as robot-assisted radical cystectomy, robot-assisted partial nephrectomy, robot-assisted nephroureterectomy and robot-assisted pyeloplasty. A MEDLINE search was used to identify recent articles (within the last two years) and publications of specific importance, which highlighted the recent developments and future direction of robotics. This review will use the aforementioned urologic surgeries as vehicles to evaluate the current status and future role of robotics in the advancement of the field of urology.

robotics
prostatectomy
cystectomy
nephrectomy
nephroureterectomy
Bladder
laparoscopy
minimally invasive surgery
prostate
pyeloplasty kidney


Facile Tuning the Detection Spectrum of Organic Thin Film Photodiode via Selective Exciton Activation.

Abstract: Here, we introduce a method of tuning the high-detectivity spectra of the organic photodiode (OPD) to fabricate a thin-film filter-less full-color image sensor. The strategically introduced PIN junction enables a selective activation of excitons generated from the photons with low extinction coefficient in the active layer such that the separated holes/electrons can contribute to the external current. In addition, we show that a well-defined PIN junction blocks the injection of nonallowed charge carriers, leading to very low dark current and near-ideal diode characteristics. Consequently, the high specific detectivity over 1.0 × 1012 Jones are observed from R/G/B-selective thin-film OPDs.

photodiode
full-color image sensor
barrier height
organic semiconductor
photodetector


Low gene expression levels of activating receptors of natural killer cells (NKG2E and CD94) in patients with fulminant type 1 diabetes.

Abstract: Fulminant type 1 diabetes is an independent subtype of type 1 diabetes characterized by extremely rapid onset and absence of islet-related autoantibodies. However, detailed pathophysiology of this subtype is poorly understood. In this study, a comprehensive approach was applied to understand the pathogenesis of fulminant type 1 diabetes. We determined the genes that were differentially expressed in fulminant type 1 diabetes compared with type 1A diabetes and healthy control, using gene expression microarray in peripheral blood cells. Using volcano plot analysis, we found reduced expression of killer cell lectin-like receptor subfamily C, member 3 (KLRC3) which encodes NKG2E, a natural killer (NK) cell activating receptor, in fulminant type 1 diabetes, compared with healthy controls. This difference was confirmed by real-time RT-PCR among NK-enriched cells. The expression of KLRD1 (CD94), which forms heterodimer with NKG2E (KLRC3), was also reduced in NK-enriched cells in fulminant type 1 diabetes. Furthermore, flow cytometry showed significantly lower proportion of NK cells among peripheral blood mononuclear cells (PBMCs) in fulminant type 1 diabetes than in healthy controls. In patients with fulminant type 1 diabetes, the relative proportion of NK cells correlated significantly with the time period between onset of fever to the appearance of hyperglycemic-related symptoms. We conclude the presence of reduced NK activating receptor gene expression and low proportion of NK cells in fulminant type 1 diabetes.

Nakata|Shinsuke|S| Imagawa|Akihisa|A| Miyata|Yugo|Y| Yoshikawa|Atsushi|A| Kozawa|Junji|J| Okita|Kohei|K| Funahashi|Tohru|T| Nakamura|Seiji|S| Matsubara|Kenichi|K| Iwahashi|Hiromi|H| Shimomura|Iichiro|I|

D055654:NK Cell Lectin-Like Receptor Subfamily C

D051920:NK Cell Lectin-Like Receptor Subfamily D

D020411:Oligonucleotide Array Sequence Analysis

D020133:Reverse Transcriptase Polymerase Chain Reaction

interleukin 18 receptor accessory protein

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


Small fibre pathology in patients with fibromyalgia syndrome.

Abstract: Fibromyalgia syndrome is a clinically well-characterized chronic pain condition of high socio-economic impact. Although the pathophysiology is still unclear, there is increasing evidence for nervous system dysfunction in patients with fibromyalgia syndrome. In this case-control study we investigated function and morphology of small nerve fibres in 25 patients with fibromyalgia syndrome. Patients underwent comprehensive neurological and neurophysiological assessment. We examined small fibre function by quantitative sensory testing and pain-related evoked potentials, and quantified intraepidermal nerve fibre density and regenerating intraepidermal nerve fibres in skin punch biopsies of the lower leg and upper thigh. The results were compared with data from 10 patients with monopolar depression without pain and with healthy control subjects matched for age and gender. Neurological and standard neurophysiological examination was normal in all patients, excluding large fibre polyneuropathy. Patients with fibromyalgia syndrome had increased scores in neuropathic pain questionnaires compared with patients with depression and with control subjects (P < 0.001 each). Compared with control subjects, patients with fibromyalgia syndrome but not patients with depression had impaired small fibre function with increased cold and warm detection thresholds in quantitative sensory testing (P < 0.001). Investigation of pain-related evoked potentials revealed increased N1 latencies upon stimulation at the feet (P < 0.001) and reduced amplitudes of pain-related evoked potentials upon stimulation of face, hands and feet (P < 0.001) in patients with fibromyalgia syndrome compared to patients with depression and to control subjects, indicating abnormalities of small fibres or their central afferents. In skin biopsies total (P < 0.001) and regenerating intraepidermal nerve fibres (P < 0.01) at the lower leg and upper thigh were reduced in patients with fibromyalgia syndrome compared with control subjects. Accordingly, a reduction in dermal unmyelinated nerve fibre bundles was found in skin samples of patients with fibromyalgia syndrome compared with patients with depression and with healthy control subjects, whereas myelinated nerve fibres were spared. All three methods used support the concept of impaired small fibre function in patients with fibromyalgia syndrome, pointing towards a neuropathic nature of pain in fibromyalgia syndrome.

Üçeyler|Nurcan|N| Zeller|Daniel|D| Kahn|Ann-Kathrin|AK| Kewenig|Susanne|S| Kittel-Schneider|Sarah|S| Schmid|Annina|A| Casanova-Molla|Jordi|J| Reiners|Karlheinz|K| Sommer|Claudia|C|

fibromyalgia syndrome
quantitative sensory testing
skin biopsy
pain related evoked potentials
small fibre neuropathy


Relationship between non-high-density lipoprotein cholesterol and the long-term mortality of cardiovascular diseases: NIPPON DATA 90.

Abstract:
BACKGROUND
Non-high-density lipoprotein (HDL) cholesterol level, generally less affected by fasting status or serum triglyceride levels, may be useful for predicting future cardiovascular events in daily clinical practice. This study aimed to investigate the role of non-HDL cholesterol in the development of fatal coronary events and stroke in the general Japanese population.

METHODS AND RESULTS
From the NIPPON DATA 90 prospective cohort study, 8383 participants were followed up for 20years since 1990. After exclusion of 666 cases without lipid or covariates data, 561 cases who were 75years old or older, 274 cases with history of cardiovascular disease, and 181 cases with lipid-lowering treatment, 6701 participants were included in this analysis. Non-HDL cholesterol was defined as total cholesterol minus HDL cholesterol. Outcomes were death from coronary heart disease and stroke. During the period, 69 participants died from coronary heart disease and 112 from stroke. Compared with participants with non-HDL cholesterol level <3.9mmol/L, age- and sex-adjusted hazard ratios for mortality by coronary heart disease in those with non-HDL cholesterol levels of 3.9-4.3mmol/L, 4.4-4.8mmol/L and ≥4.9mmol/L were 1.27 (95% confidence interval [CI] 0.65-2.49), 1.81 (95% CI 0.92-3.55) and 2.40 (95% CI 1.30-4.43), respectively (P trend=0.010). This association remained significant even after adjusting for other cardiovascular risk factors (P trend=0.010). There was no clear association between non-HDL cholesterol levels and mortality by stroke (P trend=0.052).

CONCLUSIONS
Among the general Japanese population, non-HDL cholesterol levels were clearly associated with future mortality by coronary heart disease, but not by stroke.

Ito|Takahiro|T| Arima|Hisatomi|H| Fujiyoshi|Akira|A| Miura|Katsuyuki|K| Takashima|Naoyuki|N| Ohkubo|Takayoshi|T| Kadota|Aya|A| Hayakawa|Takehito|T| Kita|Yoshikuni|Y| Miyagawa|Naoko|N| Okayama|Akira|A| Okamura|Tomonori|T| Ueshima|Hirotugu|H| |||


Where wilderness, medicine, technology, and religion collide.

Abstract: We report a case of a man injured in Yosemite National Park (YNP) whose use of technology and refusal of medical care, based on his Christian Science religious beliefs, created multiple challenges to the providers working to rescue and care for him. This case illustrates how our increasingly diverse and complex world requires flexibility and openness to provide the optimal care, both in the wilderness and in the front country.

technology
religion
ethics
refusal of care
search and rescue
trauma


The Understanding Bereavement Evaluation Tool (UBET) for midwives: factor structure and clinical research applications.

Abstract:
BACKGROUND
The NMSF (2009) survey reported that bereavement midwife care was inadequate in a number of UK NHS Trusts. Using a small grant from the Scottish government, 3 experienced midwifery lecturers designed an interactive workbook called "Shaping bereavement care for midwives in clinical practice" for the purpose of improving delivery of bereavement education to student midwives. An instrument called the Understanding Bereavement Evaluation Tool (UBET) was designed to measure effectiveness of the workbook at equipping students with essential knowledge.

AIM
To assess validity and reliability of the UBET at measuring midwives' self-perceptions of knowledge surrounding delivery of bereavement care to childbearing women, partners and families who have experienced childbirth related bereavement.

METHOD
An evaluative audit using the UBET was undertaken to explore student midwives' (n=179) self perceived knowledge levels before and after the workbook intervention. Validity tests have shown that the UBET, (6-item version), could be considered a psychometrically robust instrument for assessing students' knowledge gain. PCA identified that the UBET comprised two sub-scales (theoretical knowledge base - Q 1, 2 & 3 and psychosocial elements of care delivery - Q 4, 5 & 6).

DISCUSSION
Data has shown that the easy to administer and short 6-item UBET is a valid and reliable tool for educators to measure success at delivering education using the "Shaping bereavement care for midwives in clinical practice" work book.

Hollins Martin|Caroline J|CJ|
Forrest|Eleanor|E|
Wylie|Linda|L|
Martin|Colin R|CR|

Bereavement Evaluation Midwifery Education Loss Miscarriage Stillbirth Teaching


Composite contributions of cerebrospinal fluid GABAergic neurosteroids, neuropeptide Y and interleukin-6 to PTSD symptom severity in men with PTSD.

Abstract: Given that multiple neurobiological systems, as well as components within these systems are impacted by stress, and may interact in additive, compensatory and synergistic ways to promote or mitigate PTSD risk, severity, and recovery, we thought that it would be important to consider the collective, as well as separate effects of these neurobiological systems on PTSD risk. With this goal in mind, we conducted a proof-of-concept study utilizing cerebrospinal fluid (CSF) collected from unmedicated, tobacco- and illicit substance-free men with PTSD (n = 13) and trauma-exposed healthy controls (TC) (n = 17). Thirteen neurobiological factors thought to contribute to PTSD risk or severity based on previous studies were assayed. As the small but typical sample size of this lumbar puncture study limited the number of factors that could be considered in a hierarchical regression model, we included only those five factors with at least a moderate correlation (Spearman rho > 0.30) with total Clinician-Administered PTSD Scale (CAPS-IV) scores, and that did not violate multicollinearity criteria. Three of the five factors meeting these criteria-CSF allopregnanolone and pregnanolone (Allo + PA: equipotent GABAergic metabolites of progesterone), neuropeptide Y (NPY), and interleukin-6 (IL-6)-were found to account for over 75% of the variance in the CAPS-IV scores (R2 = 0.766, F = 8.75, p = 0.007). CSF Allo + PA levels were negatively associated with PTSD severity (β = -0.523, p = 0.02) and accounted for 47% of the variance in CAPS-IV scores. CSF NPY was positively associated with PTSD severity (β = 0.410, p = 0.04) and accounted for 14.7% of the CAPS-IV variance. There was a trend for a positive association between PTSD severity and CSF IL-6 levels, which accounted for 15.3% of the variance in PTSD severity (β = 0.423, p = 0.05). Z-scores were then computed for each of the three predictive factors and used to depict the varying relative degrees to which each contributed to PTSD severity at the individual PTSD patient level. This first of its kind, proof-of-concept study bears replication in larger samples. However, it highlights the collective effects of dysregulated neurobiological systems on PTSD symptom severity and the heterogeneity of potential biological treatment targets across individual PTSD patients-thus supporting the need for precision medicine approaches to treatment development and prescribing in PTSD.

Kim|Byung Kil|BK|
Fonda|Jennifer R|JR|
Hauger|Richard L|RL|
Pinna|Graziano|G|
Anderson|George M|GM|
Valovski|Ivan T|IT|
Rasmusson|Ann M|AM|

Allo + PA, sum of allopregnanolone and pregnanolone

GC-MS, gas chromatography-mass spectrometry

HPLC, high pressure liquid chromatography


Primary Blast Exposure Increases Hippocampal Vulnerability to Subsequent Exposure: Reducing Long-Term Potentiation.

Abstract: Up to 80% of injuries sustained by U.S. soldiers in Operation Enduring Freedom and Operation Iraqi Freedom were the result of blast exposure from improvised explosive devices. Some soldiers experience multiple blasts while on duty, and it has been suggested that symptoms of repetitive blast are similar to those that follow multiple non-blast concussions, such as sport-related concussion. Despite the interest in the effects of repetitive blast exposure, it remains unknown whether an initial blast renders the brain more vulnerable to subsequent exposure, resulting in a synergistic injury response. To investigate the effect of multiple primary blasts on the brain, organotypic hippocampal slice cultures were exposed to single or repetitive (two or three total) primary blasts of varying intensities. Long-term potentiation was significantly reduced following two Level 2 (92.7 kPa, 1.4 msec, 38.5 kPa·msec) blasts delivered 24 h apart without altering basal evoked response. This deficit persisted when the interval between injuries was increased to 72 h but not when the interval was extended to 144 h. The repeated blast exposure with a 24 h interval increased microglia staining and activation significantly but did not significantly increase cell death or damage axons, dendrites, or principal cell layers. Lack of overt structural damage and change in basal stimulated neuron response suggest that injury from repetitive primary blast exposure may specifically affect long-term potentiation. Our studies suggest repetitive primary blasts can exacerbate injury dependent on the injury severity and interval between exposures.

Effgen|Gwen B|GB|
Ong|Tiffany|T|
Nammalwar|Shruthi|S|
Ortuño|Andrea I|AI|
Meaney|David F|DF|
'Dale' Bass|Cameron R|CR|
Morrison|Barclay|B|