The role of the excitation:inhibition functional balance in the mPFC in the onset of antidepressants.

Abstract: Currently available antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), generally require weeks to months to produce a therapeutic response, but the mechanism of action underlying the delayed onset of antidepressant-like action remains to be elucidated. The balance between excitatory glutamatergic pyramidal neurons and inhibitory γ-aminobutyric acid (GABA) interneurons, i.e., the excitation:inhibition functional (E:I) balance, in the medial prefrontal cortex (mPFC) is critical in regulating several behaviors and might play an important mediating role in the mechanism of rapid antidepressant-like action reported by several studies. In the present study, the multichannel electrophysiological technique was used to record the firing activities of pyramidal neurons and interneurons and investigate the effects of a single dose of fluoxetine and ketamine (both 10 mg/kg, i.p.) on the E:I functional balance in the rat mPFC after 90 min or 24 h, and the forced swimming test (FST) was used to evaluate the antidepressant-like effects of fluoxetine and ketamine. The present study also explored the effects of chronic treatment with fluoxetine (10 mg/kg, i.g.) for 7 d or 21 d on the E:I functional balance in the mPFC. The present results suggested that a single dose of ketamine could both significantly increase the firing activities of pyramidal neurons and significantly decrease the firing activities of interneurons in the mPFC and exerted significant antidepressant-like action on the FST after 90 min and 24 h, but fluoxetine had no such effects under the same conditions. However, chronic treatment with fluoxetine for 21 d (but not 7 d) could significantly affect the firing activities of pyramidal neurons and interneurons in the mPFC. Taken together, the present results indicated that rapid regulation of the E:I functional balance in the mPFC might be an important common mechanism of rapid-acting antidepressants and the delayed onset of SSRIs might be partly attributed to their inability to rapidly regulate the E:I functional balance in the mPFC. The present study provided a new entry point to the development of rapid-acting antidepressants.

Yin|Yong-Yu|YY| Wang|Yun-Hui|YH| Liu|Wen-Gang|WG| Yao|Jun-Qi|JQ| Yuan|Jin|J| Li|Ze-Han|ZH| Ran|Yu-Hua|YH| Zhang|Li-Ming|LM| Li|Yun-Feng|YF|

mPFC
Antidepressant
Ketamine
Rapid-acting
E:I balance


Patterns of recurrence and metastasis in BRCA1/BRCA2-associated breast cancers.

Abstract:
BACKGROUND
Breast cancer subtypes are associated with distinct metastatic patterns. Whether germline BRCA1/BRCA2 mutation status is independently associated with central nervous system (CNS) relapse, controlling for tumor subtype, is unknown.

METHODS
Patients who were treated at Dana-Farber Cancer Institute and diagnosed with a first locoregional recurrence (LRR) or metastasis between 1981 and 2014 were identified using 2 institutional registries: 1) patients treated for recurrent breast cancer and 2) patients who underwent BRCA testing. The frequencies of LRR, sites of metastasis, and breast cancer-specific survival from LRR or metastasis were calculated, and the factors associated with CNS recurrence were evaluated using multivariable logistic regression models.

RESULTS
The final study cohort included 30 BRCA1 mutation carriers, 32 BRCA2 mutation carriers, and 270 noncarriers. Most BRCA1 carriers (73%) had triple-negative breast cancer; whereas most BRCA2 carriers (72%) had hormone receptor-positive tumors. BRCA1 carriers frequently experienced lung and distant lymph node metastasis, whereas BRCA2 carriers and noncarriers most often experienced bone metastasis. Although CNS disease occurred frequently in both BRCA1 and BRCA2 carriers (53% BRCA1, 50% BRCA2, 25% noncarriers; P < .001), only BRCA2 mutation (P = .006) was significantly associated with CNS metastasis in multivariable analysis controlling for tumor subtype. BRCA2 mutation (P = .01), triple-negative subtype (P < .001), and the involvement of CNS (P < .001) and other non-CNS distant sites (relative to locoregional recurrence or contralateral disease; P < .001) at presentation of recurrent breast cancer were associated with risk for mortality.

CONCLUSIONS
CNS involvement is frequent in women with germline BRCA1/BRCA2 mutations who have metastatic breast cancer. BRCA2 mutation carriers had a significantly higher frequency of CNS metastasis than noncarriers when controlling for breast cancer subtype.

Song|Yun|Y|0000-0002-1822-303X
Barry|William T|WT|
Seah|Davinia S|DS|
Tung|Nadine M|NM|
Garber|Judy E|JE|
Lin|Nancy U|NU|0000-0003-2263-5413

D016543:Central Nervous System Neoplasms


Comparing The Functional Outcome Of Different Dose Regimes Of Succinylcholine When Used For Rapid Induction And Intubation.

Abstract:
BACKGROUND
This study was conducted to compare outcomes of different doses of succinylcholine, in terms of intubation condition, onset of action, duration of action and abdominal fasciculation.

METHODS
Thus, randomized control trial was conducted in the department of anaesthesia and ICU, Nishter Hospital Multan from April 2016 to November 2016. A total number of 60 patients with ASA status I and II were enrolled. All patients were divided into three groups by lottery method. Data was entered and analysed by computer software SPSS version 23.2. Descriptive variables like age and onset of action were presented as mean and SD and continues statistics like gender, abdominal fasciculation and incubation condition were presented as frequency and percentages. Chi square test and one-way ANOVA was applied to see effect modification and significance of results. The p-value 0.05 was considered as significant.

RESULTS
A Total number of 60 patients included in this study and all were female. The mean age of the patients was 28.15±4.5 years. The main outcome variables of this study were the fasciculation, satisfactory intubation, onset time (seconds) and duration of action (in minutes). In group (A) 1mg, abdominal fasciculation was found 80%, 85% and 75% in group A, B, C respectively. It was also observed that satisfactory intubation was found 90%, 80% and 30% in three groups respectively. The mean onset time was 50.95±4.6, 70.7±5.66 and 94.15±8.73 seconds in three groups respectively. Similarly, the mean duration of action was 16.1±3.76, 13.55±3.01 and 8±2.05 minutes respectively.

CONCLUSIONS
Results of our clinical trial suggest that succinylcholine in low doses shorter duration of action and low rate of abdominal fasciculation which is desirable for rapid induction but onset of action is prolonged and intubation conditions were not satisfactory predominantly. So, we concluded that low doses of succnylcholine are not so much beneficial that I can replace full doses of succinylcholine when used for rapid induction and intubation.

Ahmad|Munir|M|
Khan|Nadeem Ahmed|NA|
Furqan|Aamir|A|

Succinylcholine
Rapid induction
Intubation
Anaesthesia


Emerging Roles of Urine-Derived Components for the Management of Bladder Cancer: One Man's Trash Is Another Man's Treasure.

Abstract: Urinary bladder cancer (UBC) is the most common malignancy of the urinary tract in humans, with an estimated global prevalence of 1.1 million cases over 5 years. Because of its high rates of recurrence and resistance to chemotherapy, UBC is one of the most expensive cancers to treat, resulting in significant health care costs. The development of innovative molecular and cellular tools is necessary to refine patient stratification and help predict response to treatment. Urine is an underused resource of biological components shed from bladder tumors, such as exfoliated cells and extracellular vesicles, that could serve as molecular fingerprints and provide valuable biological insights into tumor phenotype and mechanisms of resistance to chemotherapy. Additionally, characterization of urine-derived extracellular vesicles and cells could be used as reliable biomarkers for prediction of response to neoadjuvant therapy.

bladder cancer
exosomes
one health
organoids
precision medicine


Comparative evaluation of the genomes of three common Drosophila-associated bacteria.

Abstract: Drosophila melanogaster is an excellent model to explore the molecular exchanges that occur between an animal intestine and associated microbes. Previous studies in Drosophila uncovered a sophisticated web of host responses to intestinal bacteria. The outcomes of these responses define critical events in the host, such as the establishment of immune responses, access to nutrients, and the rate of larval development. Despite our steady march towards illuminating the host machinery that responds to bacterial presence in the gut, there are significant gaps in our understanding of the microbial products that influence bacterial association with a fly host. We sequenced and characterized the genomes of three common Drosophila-associated microbes: Lactobacillus plantarum, Lactobacillus brevis and Acetobacter pasteurianus For each species, we compared the genomes of Drosophila-associated strains to the genomes of strains isolated from alternative sources. We found that environmental Lactobacillus strains readily associated with adult Drosophila and were similar to fly isolates in terms of genome organization. In contrast, we identified a strain of A. pasteurianus that apparently fails to associate with adult Drosophila due to an inability to grow on fly nutrient food. Comparisons between association competent and incompetent A. pasteurianus strains identified a short list of candidate genes that may contribute to survival on fly medium. Many of the gene products unique to fly-associated strains have established roles in the stabilization of host-microbe interactions. These data add to a growing body of literature that examines the microbial perspective of host-microbe relationships.

Drosophila Intestine Host-microbe Microbiota


Antitumor Activity of Cabazitaxel and MSC-TRAIL Derived Extracellular Vesicles in Drug-Resistant Oral Squamous Cell Carcinoma.

Abstract:
Introduction
TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) can induce apoptosis in a variety of cancer cells. However, drug resistance of tumor and short half-life seriously affects its clinical targeted therapy. Cabazitaxel (CTX) is a taxane drug, which can induce apoptosis or autophagy by inhibiting the phosphorylation of PI3K/Akt/mTOR and sensitive to some drug-resistant tumors. Therefore, we explored the possibility of developing a mesenchymal stem cell-derived exosomes (MSC-EXO) vector for oral squamous cell carcinoma (OSCC) to deliver CTX/TRAIL combinations.

Methods
After ultracentrifugation and dialysis, CTX/TRAIL loaded exosomes transfected MSC (MSCT)-derived exosome (EXO) (MSCT-EXO/CTX) were isolated and purified. The expression of CD63, CD9 and TRAIL was detected by BCA to confirm the origin of EXO. High-performance liquid chromatography (HPLC) was used to determine the drug loading of VPF and draw the in vitro release profile. MTT assay, flow cytometry and Western blot were used to detect the antitumor effect of MSCT-EXO/CTX in vitro. Subsequently, the antitumor effect of MSCT-EXO/CTX in vivo was verified by mouse model.

Results
The diameter of the membrane particles was about 60-150 nm. We have proved that the incorporation and release of CTX in MSCT-EXO can inhibit the activation of PI3K, Akt and mTOR, which is a possible synergistic mechanism of CTX. MSCT-EXO and CTX can induce the apoptosis of SCC25 tumor cells in a dose-dependent manner and exert a good synergistic effect in the proportion range of 10:1-5:1. The inherent activity of MSCT-EXO and the direct effect of MSCT-EXO/CTX on OSCC confirm that MSCT-EXO/CTX makes MSCT-EXO and CTX have an efficient synergistic effect and a highly effective pharmacological inhibition on cancer cells, as verified by the subsequent mouse model. MSCT-EXO/CTX showed the lowest relative tumor volume and the highest tumor inhibition rate (P<0.05) in vivo.

Conclusion
An MSCT-EXO-based CTX delivery system might be an effective anticancer method.

Qiu|Yongle|Y| Sun|Jieming|J| Qiu|Junping|J| Chen|Guoling|G| Wang|Xiao|X| Mu|Yaxu|Y| Li|Kunshan|K| Wang|Wenjing|W|

cabazitaxel
extracellular vesicles
oral squamous cell carcinoma
mesenchymal stromal cells


Antibiotics in Leachates from Landfills in Northern Zhejiang Province, China.

Abstract: The concentrations and distributions of five sulfonamide, three tetracycline, and two macrolide antibiotics in leachates from three landfill sites in northern Zhejiang Province, China, were determined by solid-phase extraction and ultra-high performance liquid chromatography mass spectrometry. Most of the antibiotics were detected in the leachate samples. The concentrations and distributions of the antibiotics in leachates of different ages were very different. The total sulfonamide, tetracycline, and macrolide concentrations in the leachates ranged from not detected to 1.57 × 103, not detected to 5.19 × 103, and 7.30 to 5.42 × 102 ng/L, respectively. The total concentrations of detectable antibiotics were higher in fresh leachates than aged and middle-aged leachates. Higher TC-group concentrations were found in the leachates than have been found in previously published studies of landfill leachates in China. The results improve our understanding of and ability to manage antibiotic residues in landfills.

Fang|Chengran|C| Chen|Binhui|B| Zhuang|Haifeng|H| Mao|Hongzhi|H|

D000900:Anti-Bacterial Agents
D002681:China
D004784:Environmental Monitoring
D012037:Refuse Disposal
D052616:Solid Phase Extraction
D064091:Waste Disposal Facilities
D014874:Water Pollutants, Chemical

Antibiotics Leachate Landfill China Refuse


First report of Black Scurf caused by Rhizoctonia solani AG-3 on potato tubers in Mauritius.

Abstract: Potato (Solanum tuberosum L.) is considered as one of the most economically important non-sugar food crops in Mauritius, with annual production of over 14,000 tonnes (Statistics Mauritius 2018). In September 2019, in a seed potato field located in St Pierre, approximately 10% of tubers showed the presence of numerous irregular-shaped black scurf lesions on the surface. After surface sterilization of tubers with 70% alcohol, the presumed sclerotia were directly transferred to chloramphenicol amended Potato Dextrose Agar (PDA) and incubated for 5 days at 25oC in the dark. From all sampled tubers, only fast-growing, pale brown Rhizoctonia - like colonies grew, from which hyphal-tip isolates with uniform morphology were obtained. Following staining with aniline blue using the clean slide technique, cells of the isolate were observed to be multinucleate, with typical characteristics of Rhizoctonia solani AG-3 including hyphal branching at right angles, slight constriction and septum near the branch base, presence of typical monilioid cells and formation of light-brown irregular-shaped sclerotia of average size 2 mm (Tsror 2010). Identification was further conducted by sequencing of ITS rDNA region. Total DNA was extracted directly from mycelium using a DNeasy Plant Mini Kit (Qiagen, Hilden, Germany), following the manufacturer's instructions. PCR amplification and sequencing were performed with primers ITS1-F (5'-CTTGGTCATTTAGAGGAAGTAA-3') (Gardes and Bruns 1993) and ITS-4 (5'-TCCTCCGCTTATTGATATGC-3') (White et al. 1990). The nucleotide sequence of the representative isolate 448G-19/M (Accession No. MT523021) was compared with those available in GenBank and shared 99-100% identity with over 20 R. solani AG-3 isolates (100% with isolate 16-107, Salamone and Okubara 2020). Therefore, based on the morphological characteristics and sequence homology, the isolate was identified as R. solani AG-3. Koch's postulates were confirmed for the isolate by carrying out the pathogenicity tests. Twenty healthy, unwounded tubers were disinfected for 1 min with 50% commercial bleach (2% NaOCl) and individually placed in pots (20 cm ø) containing sterile substrate. Ten tubers were inoculated by placing colony fragments of 7 day-old cultures of isolate 448G-19/M near each tuber during planting. Similarly, 10 tubers inoculated with sterile PDA served as negative control. Plants were maintained in a greenhouse, watered daily and assessed for the presence of symptoms 60 days post emergence. All inoculated plants exhibited partial root necrosis while progeny tubers showed black scurf due to presence of sclerotia. Control plants remained symptomless. From all symptomatic tubers, the original isolate was successfully recovered and identified by the morphological and molecular characteristics mentioned above, thus fulfilling Koch's postulates. Although occurrence of potato black scurf had previously been observed in Mauritius (Anonymous 1927), to the best of our knowledge, this the first report confirming R. solani AG-3 as causal agent of black scurf on seed tubers in Mauritius. Early detection of R. solani AG-3 during potato seed production is necessary to prevent its dispersal via infected tubers to other fields around the island. This research is significant as it will contribute to the body of knowledge on potato pathology in Mauritius and at the same time assist in reducing losses associated with this important crop.

Takooree|Sandhya Devi|SD|
Neetoo|Hudaa|H|
Ranghoo-Sanmukhiya|Mala|M|
Hardowar|Shane|S|
Vander Waals|Jacquie|J|
Vally|Vivian|V|
Bunwaree|Arty|A|
Vojvodić|Mira|M|
Bulajic|Aleksandra|A|

Causal Agent
Crop Type
Fungi
Pathogen detection
Subject Areas
Vegetables


Shotgun Proteomics Analysis of Estrogen Effects in the Uterus Using Two-Dimensional Liquid Chromatography and Tandem Mass Spectrometry.

Abstract: Shotgun (gel-free) proteomics is a useful approach to perform identification and relative quantification of protein in complex mixtures such as tissue homogenates, biological fluids, cell lysates, and extracellular proteins. Incorporation of separative and analytical techniques such as two-dimensional liquid chromatography at nanoscale (2D-nanoLC) coupled to tandem mass spectrometry (MS/MS analysis) into the shotgun protocol provides an excellent strategy. This chapter describes the application of the shotgun proteomics protocol to evaluate the identity and expression analysis of proteins from rat uterus after estrogen (ethinylestradiol) treatment. The steps of the protocol involve sample preparation (digestion), 2D-nanoLC-MS/MS analysis, and shotgun proteomics analysis including bioinformatics tools for data conversion, organization, and interpretation.

Proteomics
Estrogen
Uterus
Liquid chromatography
Mass spectrometry
Proteins
Rat
Peptides
“Shotgun” proteomics


DNA barcodes and morphology confirm a new species of Rheocricotopus (Psilocricotopus) orientalis group (Diptera: Chironomidae).

Abstract: Morphology and DNA barcodes confirm a new chironomid species within the Rheocricotopus (Psilocricotopus) orientalis group (Diptera: Chironomidae). Rheocricotopus (Psilocricotopus) kongi Lin et Wang sp. n. is described and illustrated based on adult male from Hainan, China. Key to adult males of the R. orientalis group is given.

Lin|Xiao-Long|XL| Yu|Hai-Jun|HJ| Wang|Qian|Q| Bu|Wen-Jun|WJ| Wang|Xin-Hua|XH|

Diptera, Taxonomy, COI, Orthocladiinae, key, China


Functional Changes in the Language Network in Response to Increased Amyloid β Deposition in Cognitively Intact Older Adults.

Abstract: Word finding symptoms are frequent early in the course of Alzheimer's disease and relate principally to functional changes in left posterior temporal cortex. In cognitively intact older adults, we examined whether amyloid load affects the network for language and associative-semantic processing. Fifty-six community-recruited subjects (52-74 years), stratified for apolipoprotein E and brain-derived neurotrophic factor genotype, received a neurolinguistic assessment, (18)F-flutemetamol positron emission tomography, and a functional MRI of the associative-semantic system. The primary measure of amyloid load was the cerebral-to-cerebellar gray matter standardized uptake value ratio in a composite cortical volume of interest (SUVR(comp)). The primary outcome analysis consisted of a whole-brain voxelwise linear regression between SUVR(comp) and fMRI response during associative-semantic versus visuoperceptual processing. Higher activity in one region, the posterior left middle temporal gyrus, correlated positively with increased amyloid load. The correlation remained significant when only the word conditions were contrasted but not for pictures. According to a stepwise linear regression analysis, offline naming reaction times correlated positively with SUVR(comp). A binary classification into amyloid-positive and amyloid-negative cases confirmed our findings. The left posterior temporal activity increase may reflect higher demands for semantic control in the presence of a higher amyloid burden.

Adamczuk|Katarzyna|K|
De Weer|An-Sofie|AS|
Nelissen|Natalie|N|
Dupont|Patrick|P|
Sunaert|Stefan|S|
Bettens|Karolien|K|
Sleegers|Kristel|K|
Van Broeckhoven|Christine|C|
Van Laere|Koen|K|
Vandenberghe|Rik|R|

Alzheimer
fMRI
semantic
18F-flutemetamol
amyloid PET


A Robust Oxygen-Carrying Hemoglobin-Based Natural Sonosensitizer for Sonodynamic Cancer Therapy.

Abstract: The development of novel sonosensitizers with outstanding reactive oxygen (ROS) generation capacity and great biocompatibility poses a significant challenge for the clinical practice of sonodynamic therapy (SDT). In this work, hemoglobin (Hb) with natural metalloporphyrin was first shown to possess great potential as a sonosensitizer. Compared with traditional organic sonosensitizers, Hb had satisfactory sono-sensitizing efficiency because four the porphyrin molecules were separated by four polypeptide chains. This effectively avoided the problem of low ROS quantum yield caused by the stacking of hydrophobic porphyrins. Meanwhile, Hb is an efficient and safe oxygen carrier that may release O2 at hypoxic tumors site, which improved tumor oxygenation and subsequently enhanced SDT efficacy. Therefore, Hb was integrated with zeolitic imidazolate framework 8 (ZIF-8) to form a nanoplatform that demonstrated a potent suppression effect on deep-seated tumors under ultrasound irradiation.

Yuan|Meng|M| Liang|Shuang|S| Zhou|Ying|Y|0000-0003-3527-1161 Xiao|Xiao|X| Liu|Bin|B| Yang|Chunzheng|C| Ma|Ping'an|P| Cheng|Ziyong|Z| Lin|Jun|J|0000-0001-9572-2134

ROS
sonodynamic therapy
hemoglobin
hypoxia
mitochondria-involved apoptosis


Readmission after major surgery: effect of the postdischarge environment.

Abstract:
BACKGROUND
Although uncoordinated postdischarge care has been associated with poor clinical outcomes, the effect of discharge to a low healthcare resource area (LHRA) on readmission remains undetermined. We sought to assess how the quality of discharge area health resources impact readmission following major surgery.

METHODS
This cross-sectional study was performed by linking Maryland state data for 2012-2015 to the Agency for Healthcare Research and Quality Area Health-Resource File. Patients undergoing one of 11 common surgical procedures were identified. Multivariable logistic regression was performed to assess the effect of discharge area health resource quality on readmission.

RESULTS
A total of 76,747 patients were identified of which 9.4% were discharged to a high healthcare resource area (HHRA), whereas 81.9% of patients were discharged to an LHRA. Perioperative morbidity and length of stay were comparable between HHRA versus LHRA patients (both P > 0.05). Among all patients, 30-d and 90-d readmission was 6.5% and 12.4%, respectively. On multivariable analysis, discharge to LHRA was independently associated with a 19% (odds ratio = 1.19; 95% CI, 1.01-1.41; P = 0.043) and 18% (odds ratio = 1.18; 95% CI, 1.04-1.33; P = 0.010) greater odds of 30-d and 90-day readmission, respectively.

CONCLUSIONS
Patients discharged to an area characterized by LHRA were more likely to be readmitted at 30 d and 90 d following index discharge.

Cerullo|Marcelo|M|
Gani|Faiz|F|
Chen|Sophia Y|SY|
Canner|Joseph K|JK|
Pawlik|Timothy M|TM|

D000328:Adult
D000368:Aged
D000369:Aged, 80 and over
D003430:Cross-Sectional Studies
D005260:Female
D006295:Health Resources
D054625:Healthcare Disparities
D006801:Humans
D016015:Logistic Models
D008297:Male
D008396:Maryland
D008875:Middle Aged
D010351:Patient Discharge
D010359:Patient Readmission
D011785:Quality Assurance, Health Care
D019984:Quality Indicators, Health Care
D012189:Retrospective Studies
D012307:Risk Factors
D013514:Surgical Procedures, Operative

Readmission
Postdischarge care
Surgical complications


Impella support and acute kidney injury during high-risk percutaneous coronary intervention: The Global cVAD Renal Protection Study.

Abstract:
BACKGROUND
Protection against acute kidney injury (AKI) has been reported with the use of Impella during high-risk percutaneous coronary intervention (HR-PCI). We sought to evaluate this finding by determining the occurrence of AKI during Impella-supported HR-PCI in patients from the Global cVAD Study and compare this incidence with their calculated AKI risk at baseline.

METHODS AND RESULTS
In this prospective, multicenter study, we enrolled 314 consecutive patients. We included 223 patients that underwent nonemergent HR-PCI supported with Impella 2.5 or Impella CP and excluded those requiring hemodialysis prior to HR-PCI (19) and those with insufficient data (72). The primary outcome was AKI postprocedurally at 48 hr versus the predicted risk of AKI according to Mehran risk score. Logistic regression analysis determined predictors of AKI. Overall, 4.9% (11) of Impella-supported patients developed AKI (exclusively stage 1) at 48 hr versus a predicted rate of 21.9%, representing a 77.6% lower AKI rate (p < .0001). In this study, no Impella-supported patients required renal replacement therapy. Estimated glomerular filtration rate (ml/min/1.73 m2 ) alone predicted AKI (adjusted odds ratio [AOR]: 4.915; 95% confidence intervals [CI]: 1.02-23.53, p = .046), and increasing contrast had insignificant effects on AKI during high-risk PCI (AOR: 1.15; 95% CI: 0.87-1.51, p = .332). In patients not protected from AKI, the postprocedure incidence of AKI was not significantly greater and did not correlate with chronic kidney disease severity.

CONCLUSION
The incidence of AKI was lower during HR-PCI than expected from current risk models. Although further exploration of this finding is warranted, these data support a new protective strategy against AKI during HR-PCI.

renal protection
contrast
hemodynamic support
left ventricular dysfunction


Large granules in the peripheral blood smear and bone marrow aspirate of a 3-year-old male with lymphadenopathy and fever.

Abstract: A 3-year-old male with oculocutaneous albinism presented with lymphadenopathy and fever. Serological testing revealed Epstein-Barr virus (EBV)-specific immunoglobulin M (IgM) and a diagnosis of infectious mononucleosis was made. A complete blood count and peripheral blood smear demonstrated mild anemia, thrombocytopenia, and neutropenia with leukocytes that contained large azurophilic and eosinophilic granules. Bone marrow examination demonstrated increased hemophagocytic histiocytes along with granulocytes that contained large eosinophilic granules. In addition to hemophagocytic lymphohistiocytosis, presumably due to acute EBV infection, the patient was diagnosed with Chediak-Higashi syndrome based on the pathognomonic granules within peripheral leukocytes and precursors. The differential diagnosis of a young patient with oculocutaneous albinism presenting with an acute viral infection includes a relatively narrow range of genetic syndromes based solely on the history of albinism. This case demonstrates the application of clinical laboratory data to presumptively diagnose Chediak-Higashi syndrome in the midst of a presentation of hemophagocytic lymphohistiocytosis secondary to acute EBV infection.

McCoy|Morgan H|MH|
Mast|Kelley|K|
Relich|Ryan F|RF|
Girgis|George|G|
Nassiri|Mehdi|M|

large granules
oculocutaneous albinism
Epstein-Barr virus
infectious mononucleosis
hemophagocytic lymphohistiocytosis
Chediak-Higashi syndrome


Very volatile organic compounds: an understudied class of indoor air pollutants.

Abstract: Very volatile organic compounds (VVOCs), as categorized by the WHO, are an important subgroup of indoor pollutants and cover a wide spectrum of chemical substances. Some VVOCs are components of products commonly used indoors, some result from chemical reactions and some are reactive precursors of secondary products. Nevertheless, there is still no clear and internationally accepted definition of VVOCs. Current approaches are based on the boiling point, and the saturation vapor pressure or refer to analytical procedures. A significant problem is that many airborne VVOCs cannot be routinely analyzed by the usually applied technique of sampling on Tenax TA® followed by thermal desorption GC/MS or by DNPH-sampling/HPLC/UV. Some VVOCs are therefore often neglected in indoor-related studies. However, VVOCs are of high significance for indoor air quality assessment and there is need for their broader consideration in measurement campaigns and material emission testing.

D000393:Air Pollutants
D016902:Air Pollution, Indoor
D004784:Environmental Monitoring
D055549:Volatile Organic Compounds

Very volatile organic compounds
Volatile organic compounds
Analytical methods
Building product emission
Guidelines
Indoor air concentrations


Comparison of Functional Outcomes Between Lumbar Interbody Fusion Surgery and Discectomy in Massive Lumbar Disc Herniation: A Retrospective Analysis.

Abstract:
STUDY DESIGN
Retrospective analysis.

OBJECTIVE
Lumbar disc herniation is one the most common condition responsible for low back and radicular pain. Although the symptoms are not proportional to the size of disc prolapse but massive disc herniation frequently needs surgical management. According to literature, the incidence of low back pain, recurrent disc herniation and segmental instability are more in discectomy whereas incidence of adjacent segment degeneration (ASD) is more after fusion surgery. There are very few studies that directly compare long-term functional outcome of both these procedures. We compared the functional outcome of both the procedures in this study.

METHODS
All patients of massive disc prolapse, operated at our center between 2011 to 2017, were contacted. All the patients underwent either discectomy or transforaminal lumbar interbody fusion (TLIF). Functional outcomes of all the patients were collected using visual analogue scale (VAS) (back), VAS (leg), modified Oswestry Disability Index (mODI), Sciatica Bothersomeness Index (SBI), and McNab's criterion. Various complications were also analyzed.

RESULTS
There were 144 patients in the discectomy group and 123 patients in the TLIF group. Mean duration of follow-up was 55.07 months and 51.86 months, respectively. Both the groups show no significant difference in VAS. Significant difference was seen in mODI and SBI favoring discectomy. McNab's criterion showed excellent result in 80% of patients of discectomy compared with 68% patients of TLIF. Overall complication rate in discectomy group was 11% whereas 13% in TLIF group.

CONCLUSION
Both show good functional outcome but better in discectomy. Recurrent herniation and instability were noticed more with discectomy and ASD was more common after fusion surgeries. The choice of procedure should be individualized, and it also depends on surgical expertise, but in developing countries where resources are constrained, discectomy should be preferred.

lumbar
fusion
discectomy
disc
massive disc herniation
TLIF


The Influence of Raster Angle and Moisture Content on the Mechanical Properties of PLA Parts Produced by Fused Deposition Modeling.

Abstract: The additive manufacturing (AM) processes and technologies of 3D-printed materials and components using fused deposition modeling (FDM) are currently very popular and widely used for building parts and prototypes. Many manufacturing parameters can affect the strength and strain of the manufactured parts. The manufacturing parameters may be altered to reach an optimum setting for highly effective parts or components. This research studies the influence of the raster angle and the moisture content percentages on the mechanical properties of 3D printed polylactic acid (PLA) material. The three raster angles tested in this research were 0°, 45°, and 90°. The moisture content of the PLA material was altered to verify its effect on the mechanical properties. Twenty-seven specimens were subjected to tensile tests to examine the effect of different manufacturing parameters. The results show the specimens with a 90° raster angle and 10% moisture content have the optimum strength and strain mechanical properties.

raster angle
moisture content
mechanical properties
PLA
fused deposition modeling
process parameters


Reconsideration of Amyloid Hypothesis and Tau Hypothesis in Alzheimer's Disease.

Abstract: The so-called amyloid hypothesis, that the accumulation and deposition of oligomeric or fibrillar amyloid β (Aβ) peptide is the primary cause of Alzheimer's disease (AD), has been the mainstream concept underlying AD research for over 20 years. However, all attempts to develop Aβ-targeting drugs to treat AD have ended in failure. Here, we review recent findings indicating that the main factor underlying the development and progression of AD is tau, not Aβ, and we describe the deficiencies of the amyloid hypothesis that have supported the emergence of this idea.

amyloid
tau
Alzheimer's disease
Aβ
APP
PHF


Screening and enzymatic activity of high-efficiency gellan lyase producing bacteria Pseudoalteromonas hodoensis PE1.

Abstract: Gellan is a widely used microbial polysaccharide and one of the more effective ways to expand its application value would be to investigate the mechanism of gellan lyase and to produce gellan oligosaccharide. In this study, efficient gellan degrading bacteria were screened. One of the strains with high efficient gellan degradation capacity was labeled PE1. Through physiological and biochemical analysis of 16S rDNA, the species was identified as Pseudoalteromonas hodoensis. The optimum conditions for enzymatic activity and how it was affected by metal ions were determined, and the results showed that the lyase activities were much higher than those of previously reported (about 20 times). The gellan degradation products were determined by thin-layer chromatography and the oligosaccharides were determined by high-efficiency liquid chromatography to analyze the action site of lyase. This study laid a solid foundation which elucidates the production and application of gellan oligosaccharides. Research highlights ● High efficiency gellan lyase producing bacteria ● Optimization of reaction conditions for gellan degradation ● Oligosaccharides were detected by TLC and HPLC to speculate the lyase action sites.

Li|Ang|A|0000-0002-5346-957X
Luo|Hangqi|H|
Hu|Tingting|T|
Huang|Jingyu|J|
Alam|Nafee-Ul|NU|
Meng|Yuan|Y|
Meng|Fenbin|F|
Korkor|Nartey Linda|NL|
Hu|Xiufang|X|
Li|Ou|O|

Gellan
gellan lyase
Pseudoalteromonas hodoensis
gellan-depolymerizing


FOXC1 Regulation of miR-31-5p Confers Oxaliplatin Resistance by Targeting LATS2 in Colorectal Cancer.

Abstract: Colorectal cancer (CRC) is the second leading cause of cancer-related illness worldwide and one of the most common malignancies. Therefore, colorectal cancer research and cases have gained increasing attention. Oxaliplatin (OXA) is currently used in first-line chemotherapy to treat stage III and stage IV metastatic CRC. However, patients undergoing chemotherapy often develop resistance to chemo drugs being used. Evidence has confirmed that microRNAs regulate downstream genes in cancer biology and thereby have roles related to tumor growth, proliferation, invasion, angiogenesis, and multi-drug resistance. The aim of our study is to establish whether miR-31-5p is an oncogene in human colorectal cancers that are resistant to OXA and further confirm its malignant phenotype-associated target molecule. From the results of miRNA microarray assay, we establish that miR-31-5p expression was upregulated in oxaliplatin-resistant (OR)-LoVo cells compared with parental LoVo cells. Moreover, through in vitro and in vivo experiments, we demonstrate that miR-31-5p and large tumor suppressor kinase 2 (LATS2) were inversely related and that miR-31-5p and Forkhead box C1 (FOXC1) were positively correlated in the same LoVo or OR-LoVo cells. Importantly, we reveal a novel drug-resistance mechanism in which the transcription factor FOXC1 binds to the miR-31 promoter to increase the expression of miR31-5p and regulate LATS2 expression, resulting in cancer cell resistance to OXA. These results suggest that miR-31-5p may be a novel biomarker involved in drug resistance progression in CRC patients. Moreover, the FOXC1/miR31-5p/LATS2 drug-resistance mechanism provides new treatment strategies for CRC in clinical trials.

Hsu|Hsi-Hsien|HH|
Kuo|Wei-Wen|WW|0000-0002-2097-2240
Shih|Hui-Nung|HN|
Cheng|Sue-Fei|SF|
Yang|Ching-Kuo|CK|
Chen|Ming-Cheng|MC|
Tu|Chuan-Chou|CC|
Viswanadha|Vijaya Padma|VP|
Liao|Po-Hsiang|PH|
Huang|Chih-Yang|CY|0000-0003-2347-0411

oxaliplatin
colorectal cancer (CRC)
microRNAs
large tumor suppressor kinase 2 (LATS2)
Forkhead box C1 (FOXC1)
drug-resistance mechanism


Comparative analysis of MicroRNA expression in dog lungs infected with the H3N2 and H5N1 canine influenza viruses.

Abstract: MicroRNAs, a class of noncoding RNAs 18 to 23 nucleotides (nt) in length, play critical roles in a wide variety of biological processes. The objective of this study was to examine differences in microRNA expression profiles derived from the lungs of beagle dogs infected with the avian-origin H3N2 canine influenza virus (CIV) or the highly pathogenic avian influenza (HPAI) H5N1 virus (canine-origin isolation strain). After dogs were infected with H3N2 or H5N1, microRNA expression in the lungs was assessed using a deep-sequencing approach. To identify the roles of microRNAs in viral pathogenicity and the host immune response, microRNA target genes were predicted, and their functions were analyzed using bioinformatics software. A total of 229 microRNAs were upregulated in the H5N1 infection group compared with those in the H3N2 infection group, and 166 microRNAs were downregulated. MicroRNA target genes in the H5N1 group were more significantly involved in metabolic pathways, such as glycerolipid metabolism and glycerophospholipid metabolism, than those in the H3N2 group. The inhibition of metabolic pathways may lead to appetite loss, weight loss and weakened immunity. Moreover, miR-485, miR-144, miR-133b, miR-4859-5p, miR-6902-3p, miR-7638, miR-1307-3p and miR-1346 were significantly altered microRNAs that potentially led to the inhibition of innate immune pathways and the heightened pathogenicity of H5N1 compared with that of H3N2 in dogs. This study deepens our understanding of the complex relationships among microRNAs, the influenza virus-mediated immune response and immune injury in dogs.

Zheng|Yun|Y| Fu|Xinliang|X| Wang|Lifang|L| Zhang|Wenyan|W| Zhou|Pei|P| Zhang|Xin|X| Zeng|Weijie|W| Chen|Jidang|J| Cao|Zongxi|Z| Jia|Kun|K| Li|Shoujun|S|

MicroRNA
H5N1
Canine influenza virus H3N2
Deep sequencing
Innate immune response


Mechanical performance and healing patterns of the novel sirolimus-eluting bioresorbable Fantom scaffold: 6-month and 9-month follow-up by optical coherence tomography in the FANTOM II study.

Abstract:
Objectives
We aimed to evaluate the mechanical properties and healing patterns 6 and 9 months after implantation of the sirolimus-eluting Fantom bioresorbable scaffold (BRS).

Background
The Fantom BRS (Reva Medical, San Diego, USA) has differentiating properties including radiopacity, strut thickness of 125 µm, high expansion capacity and has demonstrated favourable mid-term clinical and angiographic outcomes.

Methods and results
FANTOM II was a prospective, single arm study with implantation of the Fantom BRS in 240 patients with stable angina pectoris. Guidance by optical coherence tomography (OCT) was encouraged and was repeated at 6-month (cohort A) or 9-month follow-up (cohort B). Matched baseline and follow-up OCT recordings were available in 152 patients. In-scaffold mean lumen area in cohort A was 6.8±1.7 mm2 and 5.7±1.4 mm2 at baseline and follow-up (p<0.0001) and was 7.2±1.6 mm2 and 5.6±1.4 mm2 in cohort B (p<0.0001). Mean scaffold area remained stable from 7.1±1.5 mm2 at baseline to 7.2±1.4 mm2 at 6 months (p=0.12), and from 7.4±1.5 mm2 to 7.3±1.4 mm2 at 9 months. Strut malapposition was median 0.8 (IQR 0.0;3.5)% and 1.8 (IQR 0.3;6.0)% at baseline and was 0.0 (IQR 0.0;0.0)% in both groups at 6-month and 9-month follow-up. Strut tissue coverage was 98.1 (IQR 95.9;99.4)% at 6 months and 98.9 (IQR 98.3;100.0)% at 9 months.

Conclusions
The novel Fantom BRS had favourable healing patterns at 6-month and 9-month follow-up as malapposition was effectively resolved and strut coverage was almost complete. The scaffold remained stable through follow-up with no signs of systematic late recoil.

Simonsen|Jo Krogsgaard|JK|
Holck|Emil Nielsen|EN|
Carrié|Didier|D|
Frey|Norbert|N|
Lutz|Matthias|M|
Weber-Albers|Joachim|J|
Dudek|Dariusz|D|
Chevalier|Bernard|B|
Daemen|Joost|J|
Dijkstra|Jouke|J|
Fox Maule|Camilla|C|
Neghabat|Omeed|O|
Lassen|Jens Flensted|JF|
Anderson|Jeffrey|J|
Christiansen|Evald Høj|EH|
Abizaid|Alexandre|A|
Holm|Niels Ramsing|NR|

optical coherence tomography
bioresorbable scaffold
coronary artery


Understanding Negative Self-Evaluations in Borderline Personality Disorder-a Review of Self-Related Cognitions, Emotions, and Motives.

Abstract: Self-conscious emotions, such as guilt, shame, or self-disgust, as well as self-related motives, such as self-enhancement or self-verification, influence how people perceive, evaluate, memorize, and respond to self-related information. They not only influence peoples' concepts of themselves but may also affect their behavior in social environments. In the current review, we describe alterations of self-related processing in borderline personality disorder (BPD). We chose BPD as an example of a mental disorder of which impairments in self-functioning and identity constitute a major feature. Since terminology used in clinical research on self-referential processing is diverse and often confusing, we start with reviewing some of the main concepts in this area of research using a conceptual framework provided from social psychology. Most studies on self-referential processing in BPD focused on descriptions of self-esteem and revealed a negative self-concept, particularly expressed by explicitly reported low self-esteem. Moreover, self-esteem is unstable in BPD and likely reactive to self-relevant cues. BPD patients are prone to negative emotions with respect to themselves, such as self-disgust and shame. First data point to altered self-related motives, too. In conclusion, although explicit self-esteem is widely studied as a global and trait-like feature of BPD, there is a strong lack of studies that take the complexity of the construct self-esteem into account. Further studies on alterations in self-related processes are required to deepen our understanding of impairments of the self-concept in BPD and enable the improvement of psychosocial therapeutic approaches.

Guilt
Shame
Self-disgust
Self-enhancement
Self-verification
Borderline personality disorder
Self-referential processing
Self-esteem
Self-concept
Self
Self-image


Atomic Force Microscopy for Cell Membrane Investigation.

Abstract: Atomic force microscopy (AFM) is a very versatile tool for studying biological samples at nanometer-scale resolution. The cell membrane plays a key role in compartmentalization, nutrient transportation, and signal transduction, while the structural feature of both sides of the membrane remains elusive. Here we describe our methods for the preparation of the cell membrane from the red blood cells and nucleated cells. High-resolution AFM topographs reveal substructural details of both sides of the cell membrane. The structure composition of cell membrane can be directly observed by time-lapse AFM and the positional information of membrane proteins can be located by molecular recognition.

Topography and recognition imaging (TREC)


Does isolated atlantoaxial fusion result in better clinical outcome compared to occipitocervical fusion?

Abstract:
BACKGROUND
The C0 to C2 region is the keystone for range of motion in the upper cervical spine. Posterior procedures usually include a fusion of at least one segment. Atlantoaxial fusion (AAF) only inhibits any motion in the C1/C2 segment whereas occipitocervical fusion (OCF) additionally interferes with the C0/C1 segment. The purpose of our study was to investigate clinical outcome of patients that underwent OCF or AAF for upper cervical spine injuries.

METHODS
Over a 5-year period (2010-2015), consecutive patients with upper cervical spine disorders were retrospectively identified as having been treated with OCF or AAF. The Numeric Pain Rating Scale (NPRS) and the Neck Disability Index (NDI) were used to evaluate postoperative neck pain and health restrictions. Demographics, follow-up, and clinical outcome parameters were evaluated. Infection, hematoma, screw malpositioning, and deaths were used as complication variables. Follow-up was at least 6 months postoperatively.

RESULTS
Ninety-six patients (male = 42, female = 54) underwent stabilization of the upper cervical spine. OCF was performed in 44 patients (45.8%), and 52 patients (54.2%) were treated with AAF. Patients with OCF were diagnosed with more comorbidities (p = 0.01). Follow-up was shorter in the OCF group compared to the AAF group (6.3 months and 14.3 months; p = 0.01). No differences were found related to infection (OCF 4.5%; AAF 7.7%) and revision rate (OCF 13.6%; AAF 17.3%; p > 0.05). Regarding bother and disability, no differences were discovered utilizing the NDI score (AAF 21.4%; OCF 37.4%; p > 0.05). A reduction of disability measured by the NDI was observed with greater follow-up for all patients (p = 0.01).

CONCLUSION
Theoretically, AAF provides greater range of motion by preserving the C0/C1 motion segment resulting in less disability. The current study did not show any significant differences regarding clinical outcome measured by the NDI compared to OCF. No differences were found regarding complication and infection rates in both groups. Both techniques provide a stable treatment with comparable clinical outcome.

D000368:Aged
D000369:Aged, 80 and over
D001268:Atlanto-Axial Joint
D002574:Cervical Vertebrae
D005260:Female
D005500:Follow-Up Studies
D006801:Humans
D008297:Male
D008875:Middle Aged
D009777:Occipital Bone
D012189:Retrospective Studies
D013119:Spinal Cord Injuries
D013123:Spinal Fusion
D016896:Treatment Outcome

Atlantoaxial fusion
Outcome
Occipitocervical fusion
Cervical spine
Injury
Magerl-Gallie


White matter myelin profiles linked to clinical subtypes of Parkinson's disease.

Abstract:
BACKGROUND
White matter (WM) microstructural integrity is important for effective brain functioning and alterations have been shown in many neurodegenerative diseases.

PURPOSE
To investigate WM myelin profiles and their relation to clinical features of Parkinson's disease (PD).

STUDY TYPE
Retrospective cross-sectional.

POPULATION
In all, 29 PD subjects and 15 healthy controls.

FIELD STRENGTH/SEQUENCE
Multiecho GRASE with 10 msec echo spacing and echo planar imaging (EPI) diffusion-weighted (b-value = 700 with 32 gradient directions) on a 3T scanner.

ASSESSMENT
Myelin water fraction (MWF) and fractional anisotropy (FA) across 20 WM regions of interest (ROIs) were compared between groups. Partial least squares (PLS) was used to associate MWF and FA with clinical and behavioral measures.

STATISTICAL TESTS
Group comparisons were done using two-sample t-tests. PLS was assessed with permutation tests. Bootstrapping was used to investigate the robustness of imaging features.

RESULTS
No group differences in myelin content could be detected with univariate tests. A three-component PLS model linked MWF profiles to clinical phenotypes but no FA profiles. The three components appeared to follow along broad motor/nonmotor subtypes of "akinetic-rigid," "tremor-predominant," and "depression/apathy" subtypes, respectively. The first component showed associations between overall motor scores (r = -0.43, P = 0.0196) and cognitive performance (r = 0.44, P = 0.0171) with interhemispheric and long-range association fibers. A second component linked overall motor scores (r = -0.58, P = 0.0009) and tremor scores (r = -0.48, P = 0.0091) to predominantly projection fibers. The last component related depression (r = -0.60, P = 0.0006) and apathy scores (r = -0.66, P = 0.0001 and r = -49, P = 0.0072) to a mixture of association and projection fibers.

DATA CONCLUSION
MWF was robustly linked to distinct clinical subtypes of PD and may serve as an additional tool to characterize the disease.

LEVEL OF EVIDENCE
4 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;50:164-174.

Baumeister|Tobias R|TR|
Kim|Jowon L|JL|
Zhu|Maria|M|
McKeown|Martin J|MJ|

white matter
Parkinson's disease
brain
myelin water fraction
multivariate analysis


Targeting cyclin-dependent kinase 6 by vanillin inhibits proliferation of breast and lung cancer cells: Combined computational and biochemical studies.

Abstract: Cyclin-dependent kinase 6 (CDK6) is a member of serine/threonine kinase family, and its overexpression is associated with cancer development. Thus, it is considered as a potential drug target for anticancer therapies. This study showed the CDK6 inhibitory potential of vanillin using combined experimental and computational methods. Structure-based docking and 200 ns molecular dynamics simulation studies revealed that the binding of vanillin stabilizes the CDK6 structure and provides mechanistic insights into the binding mechanism. Enzyme inhibition and fluorescence-binding studies showed that vanillin inhibits CDK6 with an half maximal inhibitory concentration = 4.99 μM and a binding constant (K) 4.1 × 107 M-1 . Isothermal titration calorimetry measurements further complemented our observations. Studies on human cancer cell lines (MCF-7 and A549) showed that vanillin decreases cell viability and colonization properties. The protein expression studies have further revealed that vanillin reduces the CDK6 expression and induces apoptosis in the cancer cells. In conclusion, our study presents the CDK6-mediated therapeutic implications of vanillin for anticancer therapies.

Yousuf|Mohd|M|
Shamsi|Anas|A|
Queen|Aarfa|A|
Shahbaaz|Mohd|M|
Khan|Parvez|P|
Hussain|Afzal|A|
Alajmi|Mohamed F|MF|
Rizwanul Haque|Qazi M|QM|
Imtaiyaz Hassan|Md|M|

D000072283:A549 Cells
D001547:Benzaldehydes
D001943:Breast Neoplasms
D049109:Cell Proliferation
D051361:Cyclin-Dependent Kinase 6
D005260:Female
D057809:HEK293 Cells
D006801:Humans
D008175:Lung Neoplasms
D061986:MCF-7 Cells
D056004:Molecular Dynamics Simulation
D009363:Neoplasm Proteins

cyclin-dependent kinase 6
vanillin
anticancer-molecules
docking and MD simulations
drug design and discovery
kinase inhibitor


Influence of mini-screw implant-assisted intrusion on orthodontically induced inflammatory root resorption: a systematic review.

Abstract:
AIM
To systematically review indexed literature related to the influence of mini-screw implant (MSI)-assisted intrusion on orthodontically induced inflammatory root resorption (OIIRR).

METHODS
Indexed databases were searched without time and language restrictions using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The inclusion criteria were: (a) original studies; (b) patients/subjects undergoing MSI-assisted intrusion; and (c) tomographic and/or histological assessment of OIIRR. Letters to the Editor, commentaries, case reports/series, reviews, and studies based on two-dimensional radiographic assessment of OIIRR were excluded. For experimental and clinical studies, the risk of bias assessment was performed using the Systematic Review Centre for Laboratory animal Experimentation risk of bias tool and the Risk of Bias in Non-randomized Studies of Interventions guidelines, respectively.

RESULTS
The initial search yielded 453 studies, out of which 6 (3 clinical and 3 on animal-models) were included. The clinical studies were performed on males and females with a mean age ranging between 16.07 and 25.5 years. Duration of the clinical studies ranged from 3.8 to 9 months. The animal studies were performed on mini-pigs, rats, and dogs. The mean age in the studies on rats and mini-pigs was 2.76 and 18 months, respectively. In the study on canine models, mean age was not reported. In all studies, MSI-assisted intrusion was shown to cause OIIRR. Power analysis was performed in one study. All studies had a moderate risk of bias.

CONCLUSIONS
MSI-assisted intrusion is a risk factor for OIIRR; however, from a clinical perspective, further well-designed and power-adjusted studies are needed.

Intrusion
Orthodontic
Root resorption
Mini-screw implants


The Good, the Bad, and the Irrelevant: Neural Mechanisms of Learning Real and Hypothetical Rewards and Effort.

Abstract:
UNLABELLED
Natural environments are complex, and a single choice can lead to multiple outcomes. Agents should learn which outcomes are due to their choices and therefore relevant for future decisions and which are stochastic in ways common to all choices and therefore irrelevant for future decisions between options. We designed an experiment in which human participants learned the varying reward and effort magnitudes of two options and repeatedly chose between them. The reward associated with a choice was randomly real or hypothetical (i.e., participants only sometimes received the reward magnitude associated with the chosen option). The real/hypothetical nature of the reward on any one trial was, however, irrelevant for learning the longer-term values of the choices, and participants ought to have only focused on the informational content of the outcome and disregarded whether it was a real or hypothetical reward. However, we found that participants showed an irrational choice bias, preferring choices that had previously led, by chance, to a real reward in the last trial. Amygdala and ventromedial prefrontal activity was related to the way in which participants' choices were biased by real reward receipt. By contrast, activity in dorsal anterior cingulate cortex, frontal operculum/anterior insula, and especially lateral anterior prefrontal cortex was related to the degree to which participants resisted this bias and chose effectively in a manner guided by aspects of outcomes that had real and more sustained relationships with particular choices, suppressing irrelevant reward information for more optimal learning and decision making.

SIGNIFICANCE STATEMENT
In complex natural environments, a single choice can lead to multiple outcomes. Human agents should only learn from outcomes that are due to their choices, not from outcomes without such a relationship. We designed an experiment to measure learning about reward and effort magnitudes in an environment in which other features of the outcome were random and had no relationship with choice. We found that, although people could learn about reward magnitudes, they nevertheless were irrationally biased toward repeating certain choices as a function of the presence or absence of random reward features. Activity in different brain regions in the prefrontal cortex either reflected the bias or reflected resistance to the bias.

Scholl|Jacqueline|J|
Kolling|Nils|N|
Nelissen|Natalie|N|
Wittmann|Marco K|MK|
Harmer|Catherine J|CJ|
Rushworth|Matthew F S|MF|

learning
hypothetical
reward
effort
frontal pole
vmPFC


Correlation Between Subjective Happiness and Pleasant Activities at Workplace in Nursing Staff for Older Individuals in Japan.

Abstract: The purpose of this study was to investigate the correlations between nursing staff's mental health, number of years worked, night shifts performed, and pleasant activities at the workplace. One hundred forty-three subjects who had no missing data were analyzed. Questions consisted of basic attributes, subjective happiness scale (SHS), and pleasant activities conducted at the workplace. Denouements of SHS indicated a significant trend for the main effect, with more pleasant activities in the high SHS group than the low SHS group. The interaction was significant, with fewer pleasant activities in participants in the low SHS group who worked the night shift compared with those who worked the night shift regardless of work experience. The outcomes of this study suggest that it is essential to expand the repertoire of pleasant activities at the workplace to increase the subjective happiness of nursing staff for older individuals.

Takeda|Shinya|S|0000-0001-8856-2371
Nakayama|Shigeki|S|
Uddin|Md Sahab|MS|
Hiramoto|Atsumi|A|
Inoue|Masahiko|M|

Subjective happiness
Pleasant activities
Workplace
Nursing staff
Mental health


Surgical correction is ineffective for improvement of dyssynergic defecation in patients with rectal prolapse.

Abstract:
BACKGROUND/AIMS
The patients with rectal prolapse suffer from not only a prolapse rectum but also associated dysfunction. However, most surgical techniques are successful regarding the prolapse, but either do not solve or even worsen defecation dysfunction. The purpose of this study was to investigate the functional and physiological results after surgical correction in patients with rectal prolapse.

METHODS
This study is a retrospective review of a single-institution experience. Patients with rectal prolapse who underwent anorectal manometry before and after Delorme's procedure were included. The primary outcomes measured were improvement of clinical symptoms and physiologic study.

RESULTS
Consecutive 19 patients with rectal prolapse (17 females, mean age of 68.1 ± 10.8 years) underwent anorectal manometry before and after Delorme's procedure. The two most prevalent symptoms before operation were rectal tenesmus (15/19, 78.9%) and excessive straining (13/19, 68.4%). The two most prevalent symptoms after operation were rectal tenesmus (14/19, 73.6%) and excessive straining (13/19, 68.4%). No significant differences in resting anal pressure, squeezing anal pressure, defecation index, and rectal sense were found postoperatively. However, vector asymmetry index before surgery was higher than that after surgery (35.0 vs. 32.0, P = 0.018). Ten patients (52.5%) had type I dyssynergic defecation before surgery. No improvement of dyssynergic pattern occurred after surgery.

CONCLUSIONS
In conclusion, dyssynergic defecation was not improved after reduction of rectal prolapse in patients with rectal prolapse. Further study about combination treatment with biofeedback therapy in these subgroups may be necessary.

Park|Seon-Young|SY| Cho|Sung-Bum|SB| Park|Chang-Hwan|CH| Joo|Jae-Kyun|JK| Joo|Young-Eun|YE| Kim|Hyun-Soo|HS| Choi|Sung-Kyu|SK| Rew|Jong-Sun|JS|


Annexin-A6 in Membrane Repair of Human Skeletal Muscle Cell: A Role in the Cap Subdomain.

Abstract: Defects in membrane repair contribute to the development of some muscular dystrophies, highlighting the importance to decipher the membrane repair mechanisms in human skeletal muscle. In murine myofibers, the formation of a cap subdomain composed notably by annexins (Anx) is critical for membrane repair. We applied membrane damage by laser ablation to human skeletal muscle cells and assessed the behavior of annexin-A6 (AnxA6) tagged with GFP by correlative light and electron microscopy (CLEM). We show that AnxA6 was recruited to the site of membrane injury within a few seconds after membrane injury. In addition, we show that the deficiency in AnxA6 compromises human sarcolemma repair, demonstrating the crucial role played by AnxA6 in this process. An AnxA6-containing cap-subdomain was formed in damaged human myotubes in about one minute. Through transmission electron microscopy (TEM), we observed that extension of the sarcolemma occurred during membrane resealing, which participated in forming a dense lipid structure in order to plug the hole. By properties of membrane folding and curvature, AnxA6 helped in the formation of this tight structure. The compaction of intracellular membranes-which are used for membrane resealing and engulfed in extensions of the sarcolemma-may also facilitate elimination of the excess of lipid and protein material once cell membrane has been repaired. These data reinforce the role played by AnxA6 and the cap subdomain in membrane repair of skeletal muscle cells.

Croissant|Coralie|C| Gounou|Céline|C| Bouvet|Flora|F| Tan|Sisareuth|S| Bouter|Anthony|A|0000-0002-0068-2780

D017304:Annexin A5
D017317:Annexin A6
D002460:Cell Line
D002462:Cell Membrane
D049452:Green Fluorescent Proteins
D006801:Humans
D008954:Models, Biological
D032342:Muscle Cells
D018485:Muscle Fibers, Skeletal
D018482:Muscle, Skeletal
D032446:Myoblasts
D000072417:Protein Domains
D013347:Subcellular Fractions

annexin-A6
membrane repair
human skeletal muscle
cap subdomain
electron microscopy
CLEM
fluorescence


Evolution of randomized, controlled studies of medical therapy in chronic thromboembolic pulmonary hypertension.

Abstract: Although pulmonary endarterectomy (PEA) is the treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH), many patients have inoperable disease, and some have persistent or recurrent pulmonary hypertension (PH) after surgery. Alternative options (balloon pulmonary angioplasty (BPA) and PH-targeted medical therapy) are, therefore, required. Studies of medical therapies for CTEPH have evolved since Aerosolized Iloprost Randomized (AIR), the first randomized, controlled study of a PH-targeted therapy (inhaled iloprost) to include patients with CTEPH. Key learnings from these studies include the need to evaluate CTEPH separately from other types of PH, the importance of prospective operability adjudication as part of the protocol, and the need for sufficient duration to allow treatment benefits to become apparent. The 16-week Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase-Stimulator Study 1 (CHEST-1) study was the first to operationalize these learnings, demonstrating a significant mean improvement in 6-minute walk distance (+46 m) and improvements in hemodynamic endpoints with riociguat versus placebo. Findings from previous studies will inform the design of future studies to address key issues related to combination medical therapy. Data on combinations of macitentan with phosphodiesterase type 5 inhibitors or oral prostanoids are available from MERIT, the first study to allow such regimens. No data on combinations including riociguat, the only licensed medical therapy for CTEPH, are available. Studies are also needed for multimodality treatment, including medical therapy plus BPA, and medical therapy as a bridge to PEA in selected operable patients. To address these issues and improve patient outcomes, it is vital that we learn from current studies to improve future trial design.


Tale of a Wandering Lead: Late Atrial Lead Perforation into Right Lung following Pacemaker Implantation.

Abstract: Cardiac perforation by a pacemaker lead is a rare complication of pacemaker implantation. Presentation can vary from chest pain and shortness of breath to the patient being completely asymptomatic. Diagnosis is usually made by high-resolution computed tomography (HRCT) scan of the chest. Electrocardiograph (EKG) usually shows the absence of a paced rhythm, but it doesn't provide a definitive diagnosis. We describe a case of late cardiac perforation by an atrial pacemaker lead with no signs or symptoms of pericardial tamponade.

Saradna|Arjun|A| Sinha|Ankur|A| Abduraimova|Madina|M| Rodriguez|Daniel|D| Yang|Felix|F|

perforation lung pacemaker displaced penetrating


Early Experience With Methylprednisolone on SARS-CoV-2 Infection in the African American Population, a Retrospective Analysis.

Abstract:
Background
Coronavirus disease-19 (COVID-19) is associated with acute kidney injury (AKI) and acute respiratory distress syndrome (ARDS) with high mortality rates. In African American (AA) populations, COVID-19 presentations and outcomes are more severe. NIH and Interim WHO guidelines had suggested against the use of corticosteroids unless in clinical trials until the recent publication of the RECOVERY trial. Here, we analyzed the treatment effect of methylprednisolone on patients with AKI and ARDS during the initial 2 months of COVID-19 and detail the learning effect within our institution.

Methods
Between March 1 and April 30, 2020, 75 AA patients met our inclusion criteria for ARDS and AKI, of which 37 had received corticosteroids. Twenty-eight-day mortality, improvement in PaO2/FiO2 ratio, and renal function were analyzed. The impact of methylprednisolone treatment was assessed with multivariable methods.

Results
Survival in the methylprednisolone group reached 51% at 21 days compared to 29% in the non-corticosteroid group (P < .001). Methylprednisolone improved the likelihood of renal function improvement. PaO2/FiO2 ratio in the methylprednisolone group improved by 73% compared to 45% in the non-corticosteroid group (P = .01). Age, gender, BMI, preexisting conditions, and other treatment factors did not show any impact on renal or PaO2/FiO2 ratio improvement. The use of anticoagulants, the month of treatment, and AKI during hospitalization also influenced outcomes.

Conclusion
In AA COVID-19 positive patients with ARDS and AKI, IV methylprednisolone lowered the incidence of mortality and improved the likelihood of renal and lung function recovery. Further investigation with a randomized control trial of corticosteroids is warranted.

methylprednisolone
COVID-19
acute kidney injury
acute respiratory distress syndrome


Current standards of neuropsychological assessment in epilepsy surgery centers across Europe.

Abstract: We explored the current practice with respect to the neuropsychological assessment of surgical epilepsy patients in European epilepsy centers, with the aim of harmonizing and establishing common standards. Twenty-six epilepsy centers and members of "E-PILEPSY" (a European pilot network of reference centers in refractory epilepsy and epilepsy surgery), were asked to report the status of neuropsychological assessment in adults and children via two different surveys. There was a consensus among these centers regarding the role of neuropsychology in the presurgical workup. Strong agreement was found on indications (localization, epileptic dysfunctions, adverse drugs effects, and postoperative monitoring) and the domains to be evaluated (memory, attention, executive functions, language, visuospatial skills, intelligence, depression, anxiety, and quality of life). Although 186 different tests are in use throughout these European centers, a core group of tests reflecting a moderate level of agreement could be discerned. Variability exists with regard to indications, protocols, and paradigms for the assessment of hemispheric language dominance. For the tests in use, little published evidence of clinical validity in epilepsy was provided. Participants in the survey reported a need for improvement concerning the validity of the tests, tools for the assessment of everyday functioning and accelerated forgetting, national norms, and test co-normalization. Based on the present survey, we documented a consensus regarding the indications and principles of neuropsychological testing. Despite the variety of tests in use, the survey indicated that there may be a core set of tests chosen based on experience, as well as on published evidence. By combining these findings with the results of an ongoing systematic literature review, we aim for a battery that can be recommended for the use across epilepsy surgical centers in Europe.

Vogt|Viola Lara|VL|
Äikiä|Marja|M|
Del Barrio|Antonio|A|
Boon|Paul|P|
Borbély|Csaba|C|
Bran|Ema|E|
Braun|Kees|K|
Carette|Evelien|E|
Clark|Maria|M|
Cross|Judith Helen|JH|
Dimova|Petia|P|
Fabo|Daniel|D|
Foroglou|Nikolaos|N|
Francione|Stefano|S|
Gersamia|Anna|A|
Gil-Nagel|Antonio|A|
Guekht|Alla|A|
Harrison|Sue|S|
Hecimovic|Hrvoje|H|
Heminghyt|Einar|E|
Hirsch|Edouard|E|
Javurkova|Alena|A|
Kälviäinen|Reetta|R|
Kavan|Nicole|N|
Kelemen|Anna|A|
Kimiskidis|Vasilios K|VK|
Kirschner|Margarita|M|
Kleitz|Catherine|C|
Kobulashvili|Teia|T|
Kosmidis|Mary H|MH|
Kurtish|Selin Yagci|SY|
Lesourd|Mathieu|M|
Ljunggren|Sofia|S|
Lossius|Morten Ingvar|MI|
Malmgren|Kristina|K|
Mameniskiené|Ruta|R|
Martin-Sanfilippo|Patricia|P|
Marusic|Petr|P|
Miatton|Marijke|M|
Özkara|Çiğdem|Ç|
Pelle|Federica|F|
Rubboli|Guido|G|
Rudebeck|Sarah|S|
Ryvlin|Philippe|P|
van Schooneveld|Monique|M|
Schmid|Elisabeth|E|
Schmidt|Pia-Magdalena|PM|
Seeck|Margitta|M|
Steinhoff|Bernhard J|BJ|
Shavel-Jessop|Sara|S|
Tarta-Arsene|Oana|O|
Trinka|Eugen|E|
Viggedal|Gerd|G|
Wendling|Anne-Sophie|AS|
Witt|Juri-Alexander|JA|
Helmstaedter|Christoph|C|
|||

Neuropsychology
Epilepsy surgery
Europe
Consensus
Diagnostic


Engineered Bio-inspired Multifunctional Peptide- and Protein-based Therapeutic Biomolecules for Better Wound Care.

Abstract: Developing non-immunogenic therapeutic biomolecules for facilitating blood clotting followed by wound healing via therapeutic angiogenesis, still remains a formidable challenge. Excessive blood loss of accident victims and battalions cause a huge number of deaths worldwide. Patients with inherited bleeding disorders face acute complications during injury and post-surgery. Biologically-inspired peptide-based hemostat can act as a potential therapeutic for handling coagulopathy. Additionally, non-healing wounds for patients having ischemic diseases can cause severe clinical complications. Advancement in stabilized growth-factor-based proangiogenic therapy may offer effective possibilities for the treatment of ischemic pathology. This review will discuss nature-inspired biocompatible stabilized peptide- and protein-based molecular medicines to serve unmet medical challenges for handling traumatic coagulopathy and impaired wound healing.

wound healing
blood-clotting
growth factor mimetics
peptide
sealant


Principles of Whole-Genome Amplification.

Abstract: Modern molecular biology relies on large amounts of high-quality genomic DNA. However, in a number of clinical or biological applications this requirement cannot be met, as starting material is either limited (e.g., preimplantation genetic diagnosis (PGD) or analysis of minimal residual cancer) or of insufficient quality (e.g., formalin-fixed paraffin-embedded tissue samples or forensics). As a consequence, in order to obtain sufficient amounts of material to analyze these demanding samples by state-of-the-art modern molecular assays, genomic DNA has to be amplified. This chapter summarizes available technologies for whole-genome amplification (WGA), bridging the last 25 years from the first developments to currently applied methods. We will especially elaborate on research application, as well as inherent advantages and limitations of various WGA technologies.

Czyz|Zbigniew Tadeusz|ZT|
Kirsch|Stefan|S|
Polzer|Bernhard|B|

D021141:Nucleic Acid Amplification Techniques

Whole-genome amplification
Ligation-mediated amplification
Multiple displacement amplification
PCR-based amplification


Facile and high-efficient immobilization of histidine-tagged multimeric protein G on magnetic nanoparticles.

Abstract: This work reports the high-efficient and one-step immobilization of multimeric protein G on magnetic nanoparticles. The histidine-tagged (His-tag) recombinant multimeric protein G was overexpressed in Escherichia coli BL21 by the repeated linking of protein G monomers with a flexible linker. High-efficient immobilization on magnetic nanoparticles was demonstrated by two different preparation methods through the amino-silane and chloro-silane functionalization on silica-coated magnetic nanoparticles. Three kinds of multimeric protein G such as His-tag monomer, dimer, and trimer were tested for immobilization efficiency. For these tests, bicinchoninic acid (BCA) assay was employed to determine the amount of immobilized His-tag multimeric protein G. The result showed that the immobilization efficiency of the His-tag multimeric protein G of the monomer, dimer, and trimer was increased with the use of chloro-silane-functionalized magnetic nanoparticles in the range of 98% to 99%, rather than the use of amino-silane-functionalized magnetic nanoparticles in the range of 55% to 77%, respectively.

Immobilization
Histidine-tag
Protein G
Magnetic nanoparticle
Efficiency


The pharmacokinetics of peginterferon lambda-1a following single dose administration to subjects with impaired renal function.

Abstract:
AIMS
This open label study was conducted to assess the effect of renal impairment (RI) on the pharmacokinetics (PK) of peginterferon lambda-1a (Lambda).

METHODS
Subjects (age 18-75 years, BMI 18-35 kg m(-2) ) were enrolled into one of five renal function groups: normal (n = 12), mild RI (n = 8), moderate RI (n = 8), severe RI (n = 7), end-stage renal disease (ESRD, n = 8) based on estimated glomerular filtration rate (eGFR) calculated using the Modification of Diet in Renal Disease (MDRD) equation. Subjects received a single dose of Lambda (180 µg) subcutaneously on day 1 followed by PK serum sample collections through day 29. Safety, tolerability and immunogenicity data were collected through day 43. PK parameters were estimated and summarized by group. Geometric mean ratios (GMR) and 90% confidence intervals (CIs) were calculated between normal and RI groups.

RESULTS
With decreasing eGFR, Lambda exposure (Cmax , AUC) increased while apparent clearance (CL/F) and apparent volume of distribution (V/F) decreased. Relative to subjects with normal renal function (geometric mean AUC = 99.5 ng ml(-1) h), Lambda exposure estimates (AUC) were slightly increased in the mild RI group (geometric mean [90% CI]: 1.20 [0.82, 1.77]) and greater in the moderate (1.95 [1.35, 2.83]), severe RI (1.95 [1.30, 2.93]) and ESRD (1.88 [1.30, 2.73]) groups. Lambda was generally well tolerated.

CONCLUSIONS
The results demonstrated that RI reduces the clearance of Lambda and suggests that dose modifications may not be required in patients with mild RI but may be required in patients with moderate to severe RI or ESRD.

Hruska|Matthew W|MW|
Adamczyk|Robert|R|
Colston|Elizabeth|E|
Hesney|Michael|M|
Stonier|Michele|M|
Myler|Heather|H|
Bertz|Richard|R|

pharmacokinetics
peginterferon lambda-1a
renal impairment


Promoting a smokers' quitline in Ontario, Canada: an evaluation of an academic detailing approach.

Abstract: This study assesses the impact of an academic detailing quitline promotional outreach program on integration of patient referrals to the quitline by fax in healthcare settings and quitline utilization in Ontario, Canada. The study employed a mixed methods approach for evaluation, with trend analysis of quitline administrative data from the year before program inception (2005) to 2011 and qualitative interviews with quitline stakeholders. Participants in the qualitative interviews included academic detailing program staff, regional tobacco control stakeholders and quitline promotion experts. Quantitative outcomes included the number of fax referral partners and fax referrals received, and quitline reach. Trends in proximal and distal outreach program outcomes were assessed. The qualitative data were analysed through a process of data coding involving the constant comparative technique derived from grounded theory methods. The study identified that the outreach program has had some success in integrating the fax referral program in healthcare settings through evidence of increased fax referrals since program inception. However, organizational barriers to program partner engagement have been encountered. While referral from health professionals through the fax referral programs has increased since the inception of the outreach program, the overall reach of the quitline has not increased. The study findings highlight that an academic detailing approach to quitline promotion can have some success in achieving increased fax referral program integration in healthcare settings. However, findings suggest that investment in a comprehensive promotional strategy, incorporating academic detailing, media and the provision of free cessation medications may be a more effective approach to quitline promotion.

quitline
academic detailing
tobacco control
smoking cessation


Targeted disruption of CK1α in Toxoplasma gondii increases acute virulence in mice.

Abstract: Toxoplasma gondii, the causative agent of toxoplasmosis, encodes two casein kinase 1 (CK1) isoforms, CK1α and CK1β, with only CK1α having enzyme activity. Here we investigated the biological role of CK1α by construction of a CK1α deletion mutant (Δck1α) based on the type I parasite, and complement the mutant with restored expression of CK1α. Deletion of CK1α resulted in markedly defective parasite replication in vitro. Infected mice with Δck1α parasite caused suppression of IL-12 production, severe liver damage, higher tissue burdens, and short survival time relative to the CK1α-positive parental strain. Western blot analysis revealed that deletion of CK1α led to increased activation of the signal transducer and activator of transcription (STAT)-3 in infected mice and bone marrow-derived microphages. The transcriptome analysis showed that deletion of CK1α may increase expression of rhoptry proteins (ROPs). Western blot showed enhanced expression of ROP16 in the Δck1α parasite as compared with the wild-type and complemented parasites. These findings demonstrated that deletion of CK1α may increase acute virulence of T. gondii in mice by increased expression of ROPs, activation of STAT3, and suppression of IL-12 production, which have important implications for elucidating regulation mechanism of virulence factors for T. gondii.

Wang|Zedong|Z| Wang|Shuchao|S| Wang|Wei|W| Gu|Yi|Y| Liu|Huanhuan|H| Wei|Feng|F| Liu|Quan|Q|


Characterization of five cases of suspected bathtub suicide.

Abstract: We reviewed five autopsy cases of suspected bathtub suicide. The immediate cause of death in all cases was determined to be drowning on the basis of macropathological findings such as frothy fluid in the airways or overinflation of the lungs as well as histological findings obtained at autopsy. We suspected that the manner of death in those cases was suicide based on comprehensive postmortem investigations of statements from witnesses, the presence of a farewell letter, the fact that clothes had been worn, additional means to ensure suicide, and results of drug tests, as well as autopsy findings. Cases of bathtub suicide should be investigated carefully to distinguish them from accidental or natural death.

Murayama|Masayuki|M| Takahashi|Yoichiro|Y| Sano|Rie|R| Watanabe|Kaho|K| Takahashi|Keiko|K| Kubo|Rieko|R| Kuninaka|Hikaru|H| Kominato|Yoshihiko|Y|


Resting-State Functional Connectivity between Putamen and Salience Network and Childhood Body Mass Index.

Abstract:
INTRODUCTION
Although the putamen has a significant role in reward-seeking and motivated behaviors, including eating and food-seeking, minorities' diminished returns (MDRs) suggest that individual-level risk and protective factors have weaker effects for Non-Hispanic Black than Non-Hispanic White individuals. However, limited research is available on the relevance of MDRs in terms of the role of putamen functional connectivity on body mass index (BMI).

PURPOSE
Building on the MDRs framework and conceptualizing race and socioeconomic status (SES) indicators as social constructs, we explored racial and SES differences in the associations between putamen functional connectivity to the salience network and children's BMI.

METHODS
For this cross-sectional study, we used functional magnetic resonance imaging (fMRI) data of 6473 9-10-year-old Non-Hispanic Black and Non-Hispanic White children from the Adolescent Brain Cognitive Development (ABCD) study. The primary independent variable was putamen functional connectivity to the salience network, measured by fMRI. The primary outcome was the children's BMI. Age, sex, neighborhood income, and family structure were the covariates. Race, family structure, parental education, and household income were potential moderators. For data analysis, we used mixed-effect models in the overall sample and by race.

RESULTS
Higher right putamen functional connectivity to the salience network was associated with higher BMI in Non-Hispanic White children. The same association was missing for Non-Hispanic Black children. While there was no overall association in the pooled sample, a significant interaction was found, suggesting that the association between right putamen functional connectivity to the salience network and children's BMI was modified by race. Compared to Non-Hispanic White children, Non-Hispanic Black children showed a weaker association between right putamen functional connectivity to the salience network and BMI. While parental education and household income did not moderate our association of interest, marital status altered the associations between putamen functional connectivity to the salience network and children's BMI. These patterns were observed for right but not left putamen. Other/Mixed Race children also showed a pattern similar to Non-Hispanic Black children.

CONCLUSIONS
The association between right putamen functional connectivity to the salience network and children's BMI may depend on race and marital status but not parental education and household income. While right putamen functional connectivity to the salience network is associated with Non-Hispanic White children's BMI, Non-Hispanic Black children' BMI remains high regardless of their putamen functional connectivity to the salience network. This finding is in line with MDRs, which attributes diminished effects of individual-risk and protective factors for Non-Hispanic Black children to racism, stratification, and segregation.

functional connectivity
putamen
body mass index
children
fMRI
brain development
obesity
population groups


Monolayers of poly-L-lysine on mica--Electrokinetic characteristics.

Abstract: Physicochemical properties of poly-l-lysine and its monolayers on mica were thoroughly investigated by dynamic light scattering, electrokinetic methods and atomic force microscopy. The hydrodynamic diameter of PLL was equal to 25.5 nm within a wide range of pH and ionic strength. The electrophoretic measurements revealed that the molecules are positively charged for pH<10.5. By exploiting the electrophoretic mobility data, theelectrokinetic charge on the PLL molecules and their zeta potential were calculated. PLL monolayers of controlled coverage were deposited on mica under diffusion-controlled conditions by varying PLL bulk concentration and adsorption time. The electrokinetic characteristics of the monolayers were acquired in situ via streaming potential measurements. These studies allowed to uniquely determine the zeta potential of the monolayers as a function of pH and ionic strength. In this way the isoelectric point of the monolayers can be determined in a more convenient way compared to bulk measurements disturbed by the PLL molecule interactions. The stability of the monolayers under flow conditions was quantitatively evaluated via streaming potential measurements. The adsorption constant and the binding energy depth of PLL molecules were determined for different ionic strengths. These parameters indicate that the PLL monolayers remain stable over prolonged times.

Morga|Maria|M| Adamczyk|Zbigniew|Z| Gödrich|Sebastian|S| Oćwieja|Magdalena|M| Papastavrou|Georg|G|

Electrokinetic characteristics of poly-l-lysine molecules

Electrokinetics of poly-l-lysine monolayers

Stability of poly-l-lysine monolayers at mica

Zeta potential of poly-l-lysine monolayers at mica


Functional and physicochemical properties of flours and starches from different tuber crops.

Abstract: Flours and isolated starches from different potato and sweet potato varieties were evaluated for their physical, functional, pasting, and thermal properties. The flours had higher protein and amylose contents than starches. The L values of the starches ranged from 91.92 (S-2) to 96.42 (S-1); thus, the whiteness of the starch samples was satisfactory. X-ray diffraction mode showed that potato starch could be a special material for crystalline nanomaterials with potential industrial applications. The starches had higher viscosity than flours. Therefore, starches can be used as thickeners in different food products. The flours exhibited high gelatinization temperatures but low enthalpy, which can be attributed to the effects of non-starch components in the flours, such as proteins and lipids. Potato flours and starches exhibited higher amylose contents and pasting characteristics and wider applications in the food industry than sweet potato flours and starches. The purple-fleshed varieties had high antioxidant activity. Therefore, the colorful flours of potatoes and sweet potatoes can be combined with other cereals for the development of functional flours with nutritional applications.

Wang|Honglu|H| Yang|Qinghua|Q| Gao|Licheng|L| Gong|Xiangwei|X| Qu|Yang|Y| Feng|Baili|B|


Charging for municipal solid waste disposal in Beijing.

Abstract: Considering the various ways of Municipal Solid Waste (MSW) disposal that are currently in practice, this paper proposes a bundle pricing model of MSW disposal in Beijing, China. The bundle pricing model is set according to per capita annual disposable income, per capita annual consumption expenditure and MSW disposal cost based on the cost reimbursement principle and complementarity principle. This paper first estimates the unit costs of landfill and incineration respectively, and then designs three bundling packages according to three different income levels of households in Beijing (low-income households, middle-income households and high-income households). Specifically, based on our bundle pricing model, we propose to charge low-income households (of the average size of 3 persons) MSW fees 5.64 RMB per month, middle-income households 10.16 RMB, and high-income households 20.70 RMB per month. We also discuss and explain how the proposed mechanism can be expected to not only mitigate the capital shortage problem, but also reduce MSW quantity and improve the MSW incineration disposal technology.

Chu|Zhujie|Z| Wang|Wenna|W| Zhou|An|A| Huang|Wei-Chiao|WC|

Municipal solid waste
Bundle pricing
Landfill
Incineration
Waste disposal fee


Safety of hydroxyanthracene derivatives for use in food.

Abstract: The Panel on Food Additives and Nutrient Sources added to Food (ANS) was asked to deliver a scientific opinion on the safety of hydroxyanthracene derivatives and to provide advice on a daily intake that does not give rise to concerns about harmful effects to health. Hydroxyanthracene derivatives are a class of chemical substances naturally occurring in different botanical species and used in food to improve bowel function. The ANS Panel reviewed the available scientific data on a possible relationship between hydroxyanthracene derivatives exposure and genotoxic and carcinogenic effects. On the basis of the data currently available, the Panel noted that emodin, aloe-emodin and the structurally related substance danthron have shown evidence of in vitro genotoxicity. Aloe extracts have also been shown to be genotoxic in vitro possibly due to the presence of hydroxyanthracene derivatives in the extract. Furthermore, aloe-emodin was shown to be genotoxic in vivo and the whole-leaf aloe extract and the structural analogue danthron were shown to be carcinogenic. Epidemiological data suggested an increased risk for colorectal cancer associated with the general use of laxatives, several of which contain hydroxyanthracene derivatives. Considering the possible presence of aloe-emodin and emodin in extracts, the Panel concluded that hydroxyanthracene derivatives should be considered as genotoxic and carcinogenic unless there are specific data to the contrary, such as for rhein, and that there is a safety concern for extracts containing hydroxyanthracene derivatives although uncertainty persists. The Panel was unable to provide advice on a daily intake of hydroxyanthracene derivatives that does not give rise to concerns about harmful effects to health.

|||
Younes|Maged|M|
Aggett|Peter|P|
Aguilar|Fernando|F|
Crebelli|Riccardo|R|
Filipič|Metka|M|
Frutos|Maria Jose|MJ|
Galtier|Pierre|P|
Gott|David|D|
Gundert-Remy|Ursula|U|
Kuhnle|Gunter Georg|GG|
Lambré|Claude|C|
Leblanc|Jean-Charles|JC|
Lillegaard|Inger Therese|IT|
Moldeus|Peter|P|
Mortensen|Alicja|A|
Oskarsson|Agneta|A|
Stankovic|Ivan|I|
Waalkens-Berendsen|Ine|I|
Woutersen|Rudolf Antonius|RA|
Andrade|Raul J|RJ|
Fortes|Cristina|C|
Mosesso|Pasquale|P|
Restani|Patrizia|P|
Pizzo|Fabiola|F|
Smeraldi|Camilla|C|
Papaioannou|Adamantia|A|
Wright|Matthew|M|

hydroxyanthracene derivatives
bowel function
genotoxicity
carcinogenicity
colorectal cancer
laxatives
food supplements


Cytotoxic activity of anticancer drugs on hepatocellular carcinoma cells in hypoxic-hyponutritional culture.

Abstract: To investigate which anticancer drugs and combination of dual drugs could further promote the inhibition of cell growth in vitro against HCC cell line (HepG2) in the hypoxic and hyponutritional culture medium (HHCM) mimicked the different scenarios of transcatheter arterial chemoembolization (TACE). The cells of hepatocellular carcinoma (HCC) treated by TACE suffered various hypoxia and hyponutrition. The cells were treated for 2 hours, 4 hours, 6 hours, and 24 hours, respectively, using 10 drugs including epirubicin (EPI), cisplatin (DDP), mitomycin-C (MMC), oxaliplatin (OXA), hydroxycamptothecin (HCPT), 5-fluorouracil (5-FU), gemcitabine (GEM), docetaxel (DTX), thiotepa (TSPA), and pemetrexed disodium (PEM) in 4 concentrations of HHCM (5%, 10%, 25%, and 50%, respectively) mimicking the scenario of TACE and were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cells treated with combinations of dual drugs for 24 hours were also tested. The sensitive drugs with inhibition rates more than 30% were EPI, MMC, HCPT, OXA, and PEM in 4 types of HHCMs. The sensitivity of the cells to treatment with drugs for 24 hours was significantly higher than the sensitivity of the cells to treatment with drugs for 2 hours in 5%, 10%, and 25% HHCM. The sensitivity of the combination of dual drugs was no more than the sensitivity of the single drug with higher sensitivity in 4 concentrations of HHCM. EPI, MMC, HCPT, OXA, and PEM exhibited cytotoxic activity against HepG2 cells in various hypoxia and hyponutrition states. Prolonging the time of exposure could increase the sensitivity of drug, and the combination of dual drugs cannot enhance the cytotoxic effect.

Li|Qiang|Q| Zhu|Lin-Zhong|LZ| Yang|Ren-Jie|RJ| Zhu|Xu|X|


Effect of Atmospheric Cold Plasma Treatment on the Adhesion and Tribological Properties of Polyamide 66 and Poly(Tetrafluoroethylene).

Abstract: The surfaces of two engineering polymers including polyamide 66 (PA66) and polytetrafluoroethylene (PTFE) were treated by diffuse coplanar surface barrier discharges in atmospheric air. We found that plasma treatment improved the adhesion of PA66 for either polymer/polymer or polymer/steel joints, however, it was selective for the investigated adhesive agents. For PTFE the adhesion was unaltered for plasma treatment regardless the type of used adhesive. Tribological properties were slightly improved for PA66, too. Both the friction coefficient and wear decreased. Significant changes, again, could not be detected for PTFE. The occurred variation in the adhesion and tribology was discussed on the basis of the occurred changes in surface chemistry, wettability and topography of the polymer surface.

Károly|Zoltán|Z| Kalácska|Gábor|G| Sukumaran|Jacob|J| Fauconnier|Dieter|D|0000-0002-0257-4687 Kalácska|Ádám|Á| Mohai|Miklós|M| Klébert|Szilvia|S|0000-0002-3107-3371

diffuse coplanar surface barrier discharges (DCSBD)


Mechanisms of Desiccation Tolerance: Themes and Variations in Brine Shrimp, Roundworms, and Tardigrades.

Abstract: Water is critical for the survival of most cells and organisms. Remarkably, a small number of multicellular animals are able to survive nearly complete drying. The phenomenon of anhydrobiosis, or life without water, has been of interest to researchers for over 300 years. In this review we discuss advances in our understanding of protectants and mechanisms of desiccation tolerance that have emerged from research in three anhydrobiotic invertebrates: brine shrimp (Artemia), roundworms (nematodes), and tardigrades (water bears). Discovery of molecular protectants that allow each of these three animals to survive drying diversifies our understanding of desiccation tolerance, and convergent themes suggest mechanisms that may offer a general model for engineering desiccation tolerance in other contexts.

Hibshman|Jonathan D|JD|
Clegg|James S|JS|
Goldstein|Bob|B|

desiccation tolerance
tardigrade
anhydrobiosis
Artemia
nematode
C. elegans
LEA proteins
trehalose


Synthesis and Properties of Bis-Porphyrin Molecular Tweezers: Effects of Spacer Flexibility on Binding and Supramolecular Chirogenesis.

Abstract: Ditopic binding of various dinitrogen compounds to three bisporphyrin molecular tweezers with spacers of varying conformational rigidity, incorporating the planar enediyne (1), the helical stiff stilbene (2), or the semi-rigid glycoluril motif fused to the porphyrins (3), are compared. Binding constants Ka = 10⁴-10⁶ M(-1) reveal subtle differences between these tweezers, that are discussed in terms of porphyrin dislocation modes. Exciton coupled circular dichroism (ECCD) of complexes with chiral dinitrogen guests provides experimental evidence for the conformational properties of the tweezers. The results are further supported and rationalized by conformational analysis.

Blom|Magnus|M|
Norrehed|Sara|S|
Andersson|Claes-Henrik|CH|
Huang|Hao|H|
Light|Mark E|ME|
Bergquist|Jonas|J|
Grennberg|Helena|H|
Gogoll|Adolf|A|

D002942:Circular Dichroism
D046911:Macromolecular Substances
D008958:Models, Molecular
D015394:Molecular Structure
D011166:Porphyrins

chirogenesis
exciton coupled circular dichroism
conformational analysis
bisporphyrin tweezers
chirality transfer
host-guest chemistry
metalloporphyrins
porphyrinoids
supramolecular chemistry


Hippo signaling disruption and ovarian follicle activation in infertile patients.

Abstract: The Hippo signaling pathway, which is important in organ size regulation, is present in organisms from the fly to mammals. Disruption of the Hippo signaling pathway leads to increased nuclear translocation of the effector Yes-associated protein (YAP), resulting in the expression of cystein-rich 61, connective tissue growth factor, and nephroblastoma overexpressed (CCN) growth factors and baculoviral inhibitors of apoptosis repeat containing (BIRC) apoptosis inhibitors to increase organ sizes. Furthermore, genome-wide knockdown of genes in insect cells demonstrated that actin polymerization promoted nuclear translocation of YAP. In the mammalian ovary, we demonstrated the expression of Hippo signaling pathway genes and showed that ovarian fragmentation increased actin polymerization, leading to YAP nuclear translocation and increased expression of cystein-rich 61, CCN growth factors and BIRC apoptosis inhibitors, followed by enhanced follicle growth. Here we summarize evidence suggesting the role of mechanical stress on follicle growth in the ovary and describe recent use of ovary-damaging procedures to treat ovarian infertility. Ovarian fragmentation, together with in vitro incubation with Akt-stimulating drugs, formed the basis of an in vitro activation (IVA) therapy to treat patients with premature ovarian insufficiency, whereas ovarian fragmentation alone (drug-free IVA) was successful in treating patients with premature ovarian insufficiency with recent menses cessation. For middle-aged women with poor ovarian responses and diminished ovarian reserve, drug-free IVA was also effective in promoting follicle growth for infertility treatment. In addition, an in vivo follicle activation approach based on laparoscopic ovarian incision showed promise for patients with resistant ovary syndrome. With initial success using mechanical disruption approaches, future investigation could evaluate possibilities to refine mechanical methods and to locally administer actin polymerization-enhancing drugs for ovarian infertility treatment.

Hsueh|Aaron J W|AJW|
Kawamura|Kazuhiro|K|

Hippo signaling
ovary
premature ovarian insufficiency
drug-free IVA
diminished ovarian reserve


Clinicopathological characteristics and genetic analysis of pulmonary carcinoid tumors: A single-center retrospective cohort study and literature review.

Abstract: Pulmonary carcinoid tumors, including typical and atypical carcinoids, are well-differentiated neuroendocrine tumors (NETs) that represent 1-2% of all lung cancer cases. In the present study, all cases of well-differentiated NETs diagnosed at Tianjin Medical University General Hospital (Tianjin, China) between 2006 and 2016 were reviewed, and 20 pulmonary carcinoid cases were identified. The clinical features of these cases were summarized, and the results of pathological and imaging examinations were collated. As a low-grade malignant pulmonary neoplasm, the molecular biological mechanism of pulmonary carcinoids is yet to be elucidated. To investigate the underlying molecular mechanisms behind pulmonary carcinoids and to determine an effective molecular targeted therapeutic strategy, next-generation sequencing (NGS) was performed using tissue samples from six patients to determine additional molecular biological characteristics that may help guide targeted therapy. A total of 27 somatic mutations in 21 genes were detected. Of note, mutations in the KIT proto-oncogene receptor tyrosine kinase, Erb-B2 receptor tyrosine kinase 4, MET proto-oncogene receptor tyrosine kinase and insulin-like growth factor 1 genes occurred in two out of six cases. Since treatments for advanced carcinoids are relatively ineffective, molecular profiling may contribute to the identification of novel treatments. In addition, the literature on mutations in pulmonary carcinoids was reviewed and available clinical information and features of this tumor type were summarized.

Li|Xiongfei|X| Hou|Yuelong|Y| Shi|Tao|T| He|Yue|Y| Ren|Dian|D| Song|Zuoqing|Z| Wei|Sen|S| Chen|Gang|G| Chen|Jun|J| Xu|Song|S|

characteristics
carcinoid tumors
next-generation sequencing