Immunoreactivity of Plasminogen Activator Inhibitor 1 and Its Correlation with Dysmenorrhea and Lesional Fibrosis in Adenomyosis.

Abstract: Adenomyosis is associated with dysmenorrhea, infertility, and lesional fibrosis. The pathogenesis of adenomyosis is still unclear. Plasminogen activator inhibitor 1 (PAI-1) plays important roles in pathological activities like tumor metastasis and endometriosis. Our objective was to investigate the expression and localization of PAI-1 in eutopic and ectopic endometrium with adenomyosis and in endometrium without adenomyosis. We also sought to determine the relationship between PAI-1 immunoreactivity and the severity of dysmenorrhea and the extent of lesional fibrosis in adenomyosis. PAI-1 expression was significantly higher in the ectopic endometrium of patients with adenomyosis than in both the eutopic endometrium of patients with adenomyosis and the endometrium of controls. Ectopic PAI-1 expression correlated positively with dysmenorrhea visual analog scale (VAS) scores and the extent of lesional fibrosis in adenomyosis. High PAI-1 expression increased the likelihood of moderate to severe dysmenorrhea in adenomyosis. These results suggest that PAI-1 is involved in the adenomyosis-associated dysmenorrhea and lesional fibrosis, which provide a potential target in treating symptomatic adenomyosis.

Yang|Bingxin|B| Gu|Nihao|N| Shi|Shu|S| Zhang|Chen|C| Chen|Lan|L| Ouyang|Jing|J| Lin|Yu|Y| Sun|Feng|F| Xu|Hong|H|0000-0003-0314-9145

Dysmenorrhea Fibrosis Adenomyosis PAI-1 Immunohistochemistry


Noncoding RNAs and Intracerebral Hemorrhage.

Abstract:
BACKGROUND & OBJECTIVE
Intracerebral hemorrhage (ICH) is the most devastating subtype of stroke, for which there are few effective interventions. Computed tomography is accepted as the gold standard for diagnosis, whereas surgical evacuation is the main treatment for ICH. However, in emergency rooms, time is limited and information regarding a patient's clinical status or tolerance is typically not available. Many studies over the last decade have investigated the fundamental mechanisms of ICH and especially hematoma, which not only cause physical damage but also release toxins that have detrimental effects. However, there remain many gaps in our understanding of ICH. Compared to ischemic stroke, there is little known about the ICH pathogenesis and treatment options, and few specific biomarkers are available for monitoring disease progression, which include hematoma enlargement and perihematoma edema. Noncoding RNAs (ncRNAs) are involved in various biological processes and are potential biomarkers and therapeutic tools in central nervous system diseases. Recent studies have examined the role of ncRNAs including microRNAs, long noncoding RNAs, and circular RNAs-the three main subgroups associated with stroke-in ICH models. A deeper understanding of the functions of ncRNAs in different biological processes can provide a basis for developing more effective therapeutic strategies to prevent neuronal damage following ICH. In clinical settings, ncRNAs can serve as biomarkers for predicting the degree of injury resulting from ICH.

CONCLUSION
In this review, we discuss the current state of knowledge of the role of ncRNAs in ICH.

Li|Lingzhi|L| Wang|Pingping|P| Zhao|Haiping|H| Luo|Yumin|Y|

Intracerebral hemorrhage
circRNA
exosome
lncRNA
miRNA
transcriptome.


Identification of cell division cycle 20 as a candidate biomarker and potential therapeutic target in bladder cancer using bioinformatics analysis.

Abstract:
PURPOSE
As bladder cancer (BC) is very heterogeneous and complicated in the genetic level, exploring genes to serve as biomarkers and therapeutic targets is practical.

MATERIALS AND METHODS
We searched Gene Expression Omnibus (GEO) and downloaded the eligible microarray datasets. After intersection analysis for identified differentially expressed genes (DEGs) of included datasets, overlapped DEGs were identified and subsequently analyzed with Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Protein-Protein Interaction (PPI) and hub genes identification. Hub genes were further analyzed with mRNA expression comparation in Oncomine and Gene Expression Profiling Interactive Analysis (GEPIA) database, proteomics-based validation in The Human Protein Atlas (THPA) and survival analysis in GEO and Oncolnc database.

RESULTS
We analyzed five eligible GEO datasets and identified 76 overlapped DEGs mapped into PPI network with 459 edges which were mainly enriched in cell cycle pathway and related terms in GO and KEGG analysis. Among five identified hub genes, which are Cyclin-Dependent Kinase 1 (CDK1), Ubiquitin-Conjugating Enzyme E2 C (UBE2C), Cell Division Cycle 20 (CDC20), Microtubule Nucleation Factor (TPX2) and Cell Division Cycle Associated 8 (CDCA8); CDC20 and CDCA8 were confirmed as significant in mRNA expression comparation and proteomics-based validation. However, only CDC20 was considered prognostically significant in both GEO and Oncolnc database.

CONCLUSIONS
CDC20 and CDCA8 were identified as candidate diagnostic biomarkers for BC in the present study; however, only CDC20 was validated as prognostically valuable and may possibly serve as a candidate prognostic biomarker and potential therapeutic target. Still, further validation studies are essential and indispensable.

Shen|Peilin|P| He|Xuejun|X| Lan|Lin|L| Hong|Yingkai|Y| Lin|Mingen|M|

D015972:Gene Expression Regulation, Neoplastic

D020411:Oligonucleotide Array Sequence Analysis

Biomarker
therapeutics
Bladder cancer
Bioinformatics
CDC20


Biliary-Atresia-Associated Mannosidase-1-Alpha-2 Gene Regulates Biliary and Ciliary Morphogenesis and Laterality.

Abstract:
Background/Aims
Infectious and genetic factors are invoked, respectively in isolated biliary atresia (BA), or syndromic BA, with major extrahepatic anomalies. However, isolated BA is also associated with minor extrahepatic gut and cardiovascular anomalies and multiple susceptibility genes, suggesting common origins.

Methods
We investigated novel susceptibility genes with genome-wide association, targeted sequencing and tissue staining in BA requiring liver transplantation, independent of BA subtype. Candidate gene effects on morphogenesis, developmental pathways, and ciliogenesis, which regulates left-right patterning were investigated with zebrafish knockdown and mouse knockout models, mouse airway cell cultures, and liver transcriptome analysis.

Results
Single nucleotide polymorphisms in Mannosidase-1-α-2 (MAN1A2) were significantly associated with BA and with other polymorphisms known to affect MAN1A2 expression but were not differentially enriched in either BA subtype. In zebrafish embryos, man1a2 knockdown caused poor biliary network formation, ciliary dysgenesis in Kupffer's vesicle, cardiac and liver heterotaxy, and dysregulated egfra and other developmental genes. Suboptimal man1a2 knockdown synergized with suboptimal EGFR signaling or suboptimal knockdown of the EGFR pathway gene, adenosine-ribosylation-factor-6, which had minimal effects individually, to reproduce biliary defects but not heterotaxy. In cultured mouse airway epithelium, Man1a2 knockdown arrested ciliary development and motility. Man1a2 -/- mice, which experience respiratory failure, also demonstrated portal and bile ductular inflammation. Human BA liver and Man1a2 -/- liver exhibited reduced Man1a2 expression and dysregulated ciliary genes, known to cause multisystem human laterality defects.

Conclusion
BA requiring transplantation associates with sequence variants in MAN1A2. man1a2 regulates laterality, in addition to hepatobiliary morphogenesis, by regulating ciliogenesis in zebrafish and mice, providing a novel developmental basis for multisystem defects in BA.

So|Juhoon|J|
Ningappa|Mylarappa|M|
Glessner|Joseph|J|
Min|Jun|J|
Ashokkumar|Chethan|C|
Ranganathan|Sarangarajan|S|
Higgs|Brandon W|BW|
Li|Dong|D|
Sun|Qing|Q|
Schmitt|Lori|L|
Biery|Amy C|AC|
Dobrowolski|Steven|S|
Trautz|Christine|C|
Fuhrman|Leah|L|
Schwartz|Molly Christine|MC|
Klena|Nikolai Thomas|NT|
Fusco|Joseph|J|
Prasadan|Krishna|K|
Adenuga|Morayooluwa|M|
Mohamed|Nada|N|
Yan|Qi|Q|
Chen|Wei|W|
Horne|William|W|
Dhawan|Anil|A|
Sharif|Khalid|K|
Kelly|Deirdre|D|
Squires|Robert H|RH|
Gittes|George K|GK|
Hakonarson|Hakon|H|
Morell|Victor|V|
Lo|Cecilia|C|
Subramaniam|Shankar|S|
Shin|Donghun|D|
Sindhi|Rakesh|R|

laterality
biliary atresia
liver transplantation
biliary morphogenesis
cilia


Restoration of antitumor immunity through anti-MICA antibodies elicited with a chimeric protein.

Abstract:
BACKGROUND
Natural killer and cytotoxic CD8+ T cells are major players during antitumor immunity. They express NKG2D, an activating receptor that promotes tumor elimination through recognition of the MHC class I chain-related proteins A and B (MICA and MICB). Both molecules are overexpressed on a great variety of tumors from different tissues, making them attractive targets for immunotherapy. However, tumors shed MICA and MICB, and the soluble forms of both (sMICA and sMICB) mediate tumor-immune escape. Some reports indicate that anti-MICA antibodies (Ab) can promote the restoration of antitumor immunity through the induction of direct antitumor effects (antibody-dependent cell-mediated cytotoxicity, ADCC) and scavenging of sMICA. Therefore, we reasoned that an active induction of anti-MICA Ab with an immunogenic protein might represent a novel therapeutic and prophylactic alternative to restore antitumor immunity.

METHODS
We generated a highly immunogenic chimeric protein (BLS-MICA) consisting of human MICA fused to the lumazine synthase from Brucella spp (BLS) and used it to generate anti-MICA polyclonal Ab (pAb) and to investigate if these anti-MICA Ab can reinstate antitumor immunity in mice using two different mouse tumors engineered to express MICA. We also explored the underlying mechanisms of this expected therapeutic effect.

RESULTS
Immunization with BLS-MICA and administration of anti-MICA pAb elicited by BLS-MICA significantly delayed the growth of MICA-expressing mouse tumors but not of control tumors. The therapeutic effect of immunization with BLS-MICA included scavenging of sMICA and the anti-MICA Ab-mediated ADCC, promoting heightened intratumoral M1/proinflammatory macrophage and antigen-experienced CD8+ T cell recruitment.

CONCLUSIONS
Immunization with the chimeric protein BLS-MICA constitutes a useful way to actively induce therapeutic anti-MICA pAb that resulted in a reprogramming of the antitumor immune response towards an antitumoral/proinflammatory phenotype. Hence, the BLS-MICA chimeric protein constitutes a novel antitumor vaccine of potential application in patients with MICA-expressing tumors.

D015395:Histocompatibility Antigens Class I

D055655:NK Cell Lectin-Like Receptor Subfamily K


2018 updated European League Against Rheumatism evidence-based recommendations for the diagnosis of gout.

Abstract: Although gout is the most common inflammatory arthritis, it is still frequently misdiagnosed. New data on imaging and clinical diagnosis have become available since the first EULAR recommendations for the diagnosis of gout in 2006. This prompted a systematic review and update of the 2006 recommendations. A systematic review of the literature concerning all aspects of gout diagnosis was performed. Recommendations were formulated using a Delphi consensus approach. Eight key recommendations were generated. A search for crystals in synovial fluid or tophus aspirates is recommended in every person with suspected gout, because demonstration of monosodium urate (MSU) crystals allows a definite diagnosis of gout. There was consensus that a number of suggestive clinical features support a clinical diagnosis of gout. These are monoarticular involvement of a foot or ankle joint (especially the first metatarsophalangeal joint); previous episodes of similar acute arthritis; rapid onset of severe pain and swelling; erythema; male gender and associated cardiovascular diseases and hyperuricaemia. When crystal identification is not possible, it is recommended that any atypical presentation should be investigated by imaging, in particular with ultrasound to seek features suggestive of MSU crystal deposition (double contour sign and tophi). There was consensus that a diagnosis of gout should not be based on the presence of hyperuricaemia alone. There was also a strong recommendation that all people with gout should be systematically assessed for presence of associated comorbidities and risk factors for cardiovascular disease, as well as for risk factors for chronic hyperuricaemia. Eight updated, evidence-based, expert consensus recommendations for the diagnosis of gout are proposed.

Richette|Pascal|P|0000-0003-2132-4074
Doherty|Michael|M|
Pascual|Eliseo|E|
Barskova|Victoria|V|
Becce|Fabio|F|0000-0001-8444-8504
Castaneda|Johann|J|
Coyfish|Malcolm|M|
Guillo|Sylvie|S|
Jansen|Tim|T|
Janssens|Hein|H|
Lioté|Frédéric|F|
Mallen|Christian D|CD|
Nuki|George|G|
Perez-Ruiz|Fernando|F|
Pimentao|José|J|
Punzi|Leonardo|L|
Pywell|Anthony|A|
So|Alexander K|AK|
Tausche|Anne-Kathrin|AK|
Uhlig|Till|T|
Zavada|Jakub|J|
Zhang|Weiya|W|
Tubach|Florence|F|
Bardin|Thomas|T|0000-0002-5080-4790

gout
epidemiology
health services research


Imaging Biomarkers in Immunotherapy.

Abstract: Immune-based therapies have been in use for decades but recent work with immune checkpoint inhibitors has now changed the landscape of cancer treatment as a whole. While these advances are encouraging, clinicians still do not have a consistent biomarker they can rely on that can accurately select patients or monitor response. Molecular imaging technology provides a noninvasive mechanism to evaluate tumors and may be an ideal candidate for these purposes. This review provides an overview of the mechanism of action of varied immunotherapies and the current strategies for monitoring patients with imaging. We then describe some of the key researches in the preclinical and clinical literature on the current uses of molecular imaging of the immune system and cancer.

Juergens|Rosalyn A|RA|
Zukotynski|Katherine A|KA|
Singnurkar|Amit|A|
Snider|Denis P|DP|
Valliant|John F|JF|
Gulenchyn|Karen Y|KY|

biomarker
immunotherapy
molecular imaging


Delayed manipulation after collagenase clostridium histolyticum injection for Dupuytren contracture.

Abstract:
BACKGROUND
Collagenase clostridium histolyticum (CCH) injection for Dupuytren contracture was approved in the USA in 2010. Current FDA guidelines stipulate that finger manipulation occurs the day following injection. To investigate the safety and efficacy of delaying manipulation to 2 or 4 days following CCH injection, we conducted a prospective, randomized trial at two sites.

METHODS
Patients with Dupuytren contracture involving the metacarpophalangeal (MCP) joint ≥20° caused by a palpable cord participated. All patients received one dose of CCH (0.58 mg/0.25 ml) and were followed for 90 days. The primary end point was the percent of patients maintaining clinical success (reduction of contracture to 0°-5°) at 90 days post-injection. Adverse events and change in Michigan Hand Questionnaire (MHQ) score were recorded as secondary end points.

RESULTS
Thirty-seven patients enrolled; 13 were manipulated on day 1, 11 on day 2, and 13 on day 4. At 30 days after injection, the percentage of patients obtaining reduction of contracture to <0°-5° extension was 92, 82, and 85 % in groups 1, 2, and 3, respectively, with no significant difference. At 90 days follow-up, the percentage of patients maintaining 0°-5° extension was 91, 82, and 83 % in groups 1, 2, and 3, respectively, with no significant difference. Adverse events were comparable to rates in prior studies. There were no serious adverse events. There was no statistical difference in MHQ scores between groups at any time point.

CONCLUSIONS
Delaying manipulation to day 2 or 4 following CCH injection for MCP joint contractures does not increase adverse events or result in loss of efficacy.

LEVEL OF EVIDENCE
Therapeutic, Level II.

Kaplan|F Thomas D|FT|
Badalamente|Marie A|MA|
Hurst|Lawrence C|LC|
Merrell|Gregory A|GA|
Pahk|Raymond|R|

Collagenase clostridium histolyticum
Dupuytren contracture
Safety
Delayed finger manipulation


An alkaline phosphatase transport mechanism in the pathogenesis of Alzheimer's disease and neurodegeneration.

Abstract: Systemic inflammation is associated with loss of blood-brain barrier integrity and neuroinflammation that lead to the exacerbation of neurodegenerative diseases. It is also associated specifically with the characteristic amyloid-β and tau pathologies of Alzheimer's disease. We have previously proposed an immunosurveillance mechanism for epithelial barriers involving negative feedback-regulated alkaline phosphatase transcytosis as an acute phase anti-inflammatory response that hangs in the balance between the resolution and the progression of inflammation. We now extend this model to endothelial barriers, particularly the blood-brain barrier, and present a literature-supported mechanistic explanation for Alzheimer's disease pathology with this system at its foundation. In this mechanism, a switch in the role of alkaline phosphatase from its baseline duties to a stopgap anti-inflammatory function results in the loss of alkaline phosphatase from cell membranes into circulation, thereby decreasing blood-brain barrier integrity and functionality. This occurs with impairment of both amyloid-β efflux and tau dephosphorylating activity in the brain as alkaline phosphatase is replenished at the barrier by receptor-mediated transport. We suggest systemic alkaline phosphatase administration as a potential therapy for the resolution of inflammation and the prevention of Alzheimer's disease pathology as well as that of other inflammation-related neurodegenerative diseases.

Pike|Adrianne F|AF|
Kramer|Nynke I|NI|
Blaauboer|Bas J|BJ|
Seinen|Willem|W|
Brands|Ruud|R|

Alkaline phosphatase
Blood-brain barrier
Neuroinflammation
Neurodegenerative diseases
Alzheimer’s disease
RESCAP


MRI Investigation of the Linkage Between Respiratory Motion of the Heart and Markers on Patient's Abdomen and Chest: Implications for Respiratory Amplitude Binning List-Mode PET and SPECT Studies.

Abstract: Respiratory motion of the heart impacts the diagnostic accuracy of myocardial-perfusion emission-imaging studies. Amplitude binning has come to be the method of choice for binning list-mode based acquisitions for correction of respiratory motion in PET and SPECT. In some subjects respiratory motion exhibits hysteretic behavior similar to damped non-linear cyclic systems. The detection and correction of hysteresis between the signals from surface movement of the patient's body used in binning and the motion of the heart within the chest remains an open area for investigation. This study reports our investigation in nine volunteers of the combined MRI tracking of the internal respiratory motion of the heart using Navigators with stereo-tracking of markers on the volunteer's chest and abdomen by a visual-tracking system (VTS). The respiratory motion signals from the internal organs and the external markers were evaluated for hysteretic behavior analyzing the temporal correspondence of the signals. In general, a strong, positive correlation between the external marker motion (AP direction) and the internal heart motion (SI direction) during respiration was observed. The average ± standard deviation in the Spearman's ranked correlation coefficient (ρ) over the nine volunteer studied was 0.92 ± 0.1 between the external abdomen marker and the internal heart, and 0.87 ± 0.2 between the external chest marker and the internal heart. However despite the good correlation on average for the nine volunteers, in three studies a poor correlation was observed due to hysteretic behavior between inspiration and expiration for either the chest marker and the internal motion of the heart, or the abdominal marker and the motion of the heart. In all cases we observed a good correlation of at least either the abdomen or the chest with the heart. Based on this result, we propose the use of marker motion from both the chest and abdomen regions when estimating the internal heart motion to detect and address hysteresis when binning list-mode emission data.

Dasari|Paul|P|
Johnson|Karen|K|
Dey|Joyoni|J|
Lindsay|Clifford|C|
Shazeeb|Mohammed S|MS|
Mukherjee|Joyeeta Mitra|JM|
Zheng|Shaokuan|S|
King|Michael A|MA|

MRI
hysteresis
Cardiac respiratory motion
emission tomography
signal processing


Gait Asymmetries Persist 1 Year After Anterior Cruciate Ligament Reconstruction.

Abstract:
BACKGROUND
After anterior cruciate ligament reconstruction (ACLR), motivation to return to previous levels of activity is high. Very few studies have used return-to-activity criteria to determine when to permit athletic play. Return-to-activity measures objectively evaluate functional limb symmetry; however, previous biomechanical studies have found gait deviations in these individuals that persist up to 2 years after surgery.

PURPOSE
To evaluate gait biomechanics in a specific cohort of ACL patients 1 year after surgery and retrospectively compare individuals who pass return-to-activity criteria 6 months after surgery with those who fail.

STUDY DESIGN
Prospective analysis.

METHODS
A total of 40 athletes who participated regularly (>50 h/y) in cutting, jumping, and pivoting activities and who sustained an isolated, unilateral ACL rupture were included in this study. All participants underwent reconstruction by the same surgeon and received individualized postoperative rehabilitation. Performance-based and self-report data were measured 6 months after surgery to assess readiness to return to activity (90% outcome required to pass); 20 subjects passed return-to-activity criteria and 20 subjects did not. Motion analysis was performed 1 year after surgery, and knee flexion angles, moments, and excursions were measured during gait and evaluated for all subjects.

RESULTS
There was no limb × group interaction or effect of group for all measures. Decreased knee measures were seen on the involved limb compared with the uninvolved limb for all subjects, and failed subjects demonstrated larger differences between limbs.

CONCLUSION
Patients continued to demonstrate biomechanical limb asymmetries 1 year after ACLR, regardless of performance-based measures at 6 months. Early return to activity did not ensure limb symmetry at 1 year.

CLINICAL RELEVANCE
Gait asymmetries were seen in all subjects 1 year after surgery regardless of status at 6 months. Potentially prolonging athlete's timelines for returning to activity may prove beneficial for a successful return to activity as well as for long-term knee function.

anterior cruciate ligament
gait biomechanics
return to activity
knee flexion angle


Mutations in the BAF-Complex Subunit DPF2 Are Associated with Coffin-Siris Syndrome.

Abstract: Variants affecting the function of different subunits of the BAF chromatin-remodelling complex lead to various neurodevelopmental syndromes, including Coffin-Siris syndrome. Furthermore, variants in proteins containing PHD fingers, motifs recognizing specific histone tail modifications, have been associated with several neurological and developmental-delay disorders. Here, we report eight heterozygous de novo variants (one frameshift, two splice site, and five missense) in the gene encoding the BAF complex subunit double plant homeodomain finger 2 (DPF2). Affected individuals share common clinical features described in individuals with Coffin-Siris syndrome, including coarse facial features, global developmental delay, intellectual disability, speech impairment, and hypoplasia of fingernails and toenails. All variants occur within the highly conserved PHD1 and PHD2 motifs. Moreover, missense variants are situated close to zinc binding sites and are predicted to disrupt these sites. Pull-down assays of recombinant proteins and histone peptides revealed that a subset of the identified missense variants abolish or impaire DPF2 binding to unmodified and modified H3 histone tails. These results suggest an impairment of PHD finger structural integrity and cohesion and most likely an aberrant recognition of histone modifications. Furthermore, the overexpression of these variants in HEK293 and COS7 cell lines was associated with the formation of nuclear aggregates and the recruitment of both wild-type DPF2 and BRG1 to these aggregates. Expression analysis of truncating variants found in the affected individuals indicated that the aberrant transcripts escape nonsense-mediated decay. Altogether, we provide compelling evidence that de novo variants in DPF2 cause Coffin-Siris syndrome and propose a dominant-negative mechanism of pathogenicity.

Vasileiou|Georgia|G|
Vergarajauregui|Silvia|S|
Endele|Sabine|S|
Popp|Bernt|B|
Büttner|Christian|C|
Ekici|Arif B|AB|
Gerard|Marion|M|
Bramswig|Nuria C|NC|
Albrecht|Beate|B|
Clayton-Smith|Jill|J|
Morton|Jenny|J|
Tomkins|Susan|S|
Low|Karen|K|
Weber|Astrid|A|
Wenzel|Maren|M|
Altmüller|Janine|J|
Li|Yun|Y|
Wollnik|Bernd|B|
Hoganson|George|G|
Plona|Maria-Renée|MR|
Cho|Megan T|MT|
|||
Thiel|Christian T|CT|
Lüdecke|Hermann-Josef|HJ|
Strom|Tim M|TM|
Calpena|Eduardo|E|
Wilkie|Andrew O M|AOM|
Wieczorek|Dagmar|D|
Engel|Felix B|FB|
Reis|André|A|

DPF2
Coffin-Siris syndrome
PHD finger
BAF complex
intellectual disability
histone modification
nuclear aggregates
autism spectrum disorder
dominant negative
nail hypoplasia


Isolation and Bacteriocin-Related Typing of Streptococcus dentisani.

Abstract: Streptococcus oralis subspecies dentisani is explored as an anti-cariogenic probiotic. Here, subjecting freshly stimulated saliva samples of 35 healthy volunteers, six epidemiologically unrelated and two related strains were isolated (prevalence around 20%) applying a newly developed three-step procedure. Furthermore, the probiotic strain S. dentisani 7746 (AB-Dentisanium®) was tested under a variety of environmental conditions for its inhibitory effect on six S. mutans, two S. sobrinus, 15 other oral or intestinal streptococci, 15 S. dentisani strains, and six representatives of other species including periodontopathogens. All except one of the S. mutans strains were inhibited by 7746 colonies or culture supernatant concentrate but only if either the test cell number was low or the producer or its bacteriocin concentration, respectively, was high. S. sanguinis OMI 332, S. salivarius OMI 315, S. parasanguinis OMI 335, S. vestibularis OMI 238, and the intestinal S. dysgalactiae OMI 339 were not inhibited, while the other 10 streptococcal strains (especially S. oralis OMI 334 and intestinal S. gallolyticus OMI 326) showed a certain degree of inhibition. From the panel of other bacterial species only Aggregatibacter actinomycetemcomitans was slightly inhibited. With the exception of OMI 285 and OMI 291 that possessed a 7746 bacteriocin-like gene cluster, all S. dentisani strains and especially type strain 7747T were strongly inhibited by 7746. In conclusion, probiotic strain 7746 might antagonize the initiation and progression of dental caries by reducing S. mutans if not too abundant. S. dentisani strains inhibit each other, but strains with similar bacteriocin-related gene clusters, including immunity genes, are able to co-exist due to cross-resistance. In addition, development of resistance and adaptation to 7746-bacteriocins was observed during our study and needs attention. Hence, mechanisms underlying such processes need to be further investigated using omics-approaches. On the manufacturing level, probiotic strains should be continuously tested for function. Further clinical studies investigating inhibition of S. mutans by AB-Dentisanium® are required that should also monitor the impact on the oral microbiome composition including resident S. dentisani strains.

Conrads|Georg|G|
Westenberger|Jacqueline|J|
Lürkens|Martha|M|
Abdelbary|Mohamed M H|MMH|


Management of hot flashes in women with breast cancer receiving ovarian function suppression.

Abstract: Most breast cancers express estrogen and/or progesterone receptors, allowing the opportunity to use anti-estrogen therapies, which have demonstrated substantial efficacy in both the metastatic and adjuvant settings. Young premenopausal women with early-stage high-risk or with metastatic hormone-receptor positive breast cancer may benefit from ovarian function suppression in addition to anti-estrogen medications. While these endocrine manipulations have successfully improved breast cancer outcomes, they may lead to a significant proportion of women experiencing vasomotor symptoms. While not life-threatening, vasomotor symptoms adversely impact quality of life and can result in early treatment discontinuation. For these reasons, supportive management of this treatment-related toxicity is crucial, and clinicians caring for breast cancer patients and survivors should be familiar with the options available and the data behind them. This manuscript will review the pathophysiology, clinical manifestations, quality of life implications and non-estrogenic management options of vasomotor symptoms for women with breast cancer undergoing estrogen depletion.

Leon-Ferre|Roberto A|RA|
Majithia|Neil|N|
Loprinzi|Charles L|CL|

Hot flashes
Breast cancer
Estrogen
Vasomotor symptoms
Hot flushes
Tamoxifen


Fatty acids and related lipid mediators in the regulation of cutaneous inflammation.

Abstract: Human skin has a distinct profile of fatty acids and related bioactive lipid mediators that regulate many aspects of epidermal and dermal homeostasis, including immune and inflammatory reactions. Sebum lipids act as effective antimicrobial agents, shape immune cell communications and contribute to the epidermal lipidome. The essential fatty acid linoleic acid is crucial for the structure of the epidermal barrier, while polyunsaturated fatty acids act as precursors to eicosanoids, octadecanoids and docosanoids through cyclooxygenase, lipoxygenase and cytochrome P450 monooxygenase-mediated reactions, and endocannabinoids and N-acyl ethanolamines. Cross-communication between these families of bioactive lipids suggests that their cutaneous activities should be considered as part of a wider metabolic network that can be targeted to maintain skin health, control inflammation and improve skin pathologies.

Kiezel-Tsugunova|Magdalena|M|
Kendall|Alexandra C|AC|
Nicolaou|Anna|A|

lipid mediators
skin
cyclooxygenase
lipoxygenases
endocannabinoids
fatty acid oxidation


Effect of low-dose, repeated exposure of contaminants of emerging concern on plant development and hormone homeostasis.

Abstract: Treated wastewater is increasingly used to meet agriculture's water needs; however, treated wastewater contains numerous contaminants of emerging concern (CECs). With exposure and uptake of CECs, phytotoxicity and health of crop plants is of concern, but is poorly understood. This study evaluated the effect of low-dose, chronic exposure to a mixture of 10 CECs, including 4 antibiotics, 3 anti-inflammatory drugs, 1 antiepileptic, 1 beta-blocker, and 1 antimicrobial, on lettuce (Lactuca sativa) and cucumber (Cucumis sativa L.) plants. The CEC mixture was added in nutrient media at 1 to 20X of their typical levels in treated wastewater effluents. Biological endpoints including germination, growth, phytohormone homeostasis, and CEC bioaccumulation were determined. Exposure to the CEC mixture did not affect the germination rate of lettuce seeds, but stimulated root elongation and increased the root-to-shoot biomass ratio during a 7 d cultivation. A dose-dependent decrease in biomass was observed in cucumber seedling after a 30 d exposure, with the highest rate CEC treatment resulting in decreases of 51.2 ± 20.9, 26.3 ± 34.1, and 33.2 ± 41.7% in the below-ground, above-ground, and total biomass, respectively. Levels of abscisic acid were significantly elevated (p < 0.05) in the leaves, but decreased (p < 0.05) in the roots. The dose-response of auxin was characterized by a hormesis effect. A significant 6-fold increase in the stem auxin level was observed at the 1X CEC rate, followed by a decrease to 2-fold the control at the 20X rate. Leaf auxin concentrations also significantly increased at the 1X CEC rate to 16-fold, followed by a decrease at the highest CEC rate. The results of this study suggeste that chronic exposure to low levels of CEC mixtures may compromise the fitness of plants, and the impairments are underlined by alterations in hormone balances.

McGinnis|Michelle|M| Sun|Chengliang|C| Dudley|Stacia|S| Gan|Jay|J|

Contaminants of emerging concern
Phytotoxicity
Phytohormones
Plant uptake
Recycled water


Plasmonic Anticounterfeit Tags with High Encoding Capacity Rapidly Authenticated with Deep Machine Learning.

Abstract: Counterfeit goods create significant economic losses and product failures in many industries. Here, we report a covert anticounterfeit platform where plasmonic nanoparticles (NPs) create physically unclonable functions (PUFs) with high encoding capacity. By allowing anisotropic Au NPs of different sizes to deposit randomly, a diversity of surfaces can be facilely tagged with NP deposits that serve as PUFs and are analyzed using optical microscopy. High encoding capacity is engineered into the tags by the sizes of the Au NPs, which provide a range of color responses, while their anisotropy provides sensitivity to light polarization. An estimated encoding capacity of 270 is achieved, which is one of the highest reported to date. Authentication of the tags with deep machine learning allows for high accuracy and rapid matching of a tag to a specific product. Moreover, the tags contain descriptive metadata that is leveraged to match a tag to a specific lot number (i.e., a collection of tags created in the same manner from the same formulation of anisotropic Au NPs). Overall, integration of designer plasmonic NPs with deep machine learning methods can create a rapidly authenticated anticounterfeit platform with high encoding capacity.

Smith|Joshua D|JD|
Reza|Md Alimoor|MA|
Smith|Nathanael L|NL|
Gu|Jianxin|J|
Ibrar|Maha|M|
Crandall|David J|DJ|
Skrabalak|Sara E|SE|0000-0002-1873-100X

anticounterfeit
anisotropic nanocrystals
artificial intelligence
nanorods
plasmonic nanotechnology
security


The origins of the circumventricular organs.

Abstract: The circumventricular organs (CVOs) are specialised neuroepithelial structures found in the midline of the brain, grouped around the third and fourth ventricles. They mediate the communication between the brain and the periphery by performing sensory and secretory roles, facilitated by increased vascularisation and the absence of a blood-brain barrier. Surprisingly little is known about the origins of the CVOs (both developmental and evolutionary), but their functional and organisational similarities raise the question of the extent of their relationship. Here, I review our current knowledge of the embryonic development of the seven major CVOs (area postrema, median eminence, neurohypophysis, organum vasculosum of the lamina terminalis, pineal organ, subcommissural organ, subfornical organ) in embryos of different vertebrate species. Although there are conspicuous similarities between subsets of CVOs, no unifying feature characteristic of their development has been identified. Cross-species comparisons suggest that CVOs also display a high degree of evolutionary flexibility. Thus, the term 'CVO' is merely a functional definition, and features shared by multiple CVOs may be the result of homoplasy rather than ontogenetic or phylogenetic relationships.

Rathke's pouch
Wnts
adenohypophysis
bone morphogenetic proteins
cellular specification
fate maps
fibroblast growth factors
homeobox genes
infundibulum
pituitary gland
sonic hedgehog
tanycytes
transcription factors


Comparison of Single-Incision Laparoscopic Cholecystectomy versus Needlescopic Cholecystectomy: A Single Institutional Randomized Clinical Trial.

Abstract:
BACKGROUND
Both single-incision laparoscopic cholecystectomy (SILC) and needlescopic cholecystectomy (NSC) are superior to conventional laparoscopic cholecystectomy in terms of cosmetic outcome and incisional pain. We conducted a prospective, randomized clinical trial to evaluate the surgical outcome, postoperative pain, and cosmetic outcome for SILC and NSC procedures.

METHODS
In this trial, 105 patients were enrolled (52 in the SILC group; 53 in the NSC group). A visual analogue scale (VAS) was used to evaluate the cosmetic outcome and incisional pain for patients. Logistic regression analyses were used to evaluate the operative difficulty that was present for both procedures.

RESULTS
There were no significant differences in patient characteristics or surgical outcomes, including operative time and blood loss. The mean VAS scores for cosmetic satisfaction were similar in both groups. There were significant differences in the mean VAS scores for incisional pain on postoperative day 1 (p = 0.009), and analgesics were required within 12 h of surgery (p = 0.007). Obesity (body mass index ≥25 kg/m2) was the only significant influential factor for operating time over 100 min (p = 0.031).

CONCLUSION
NSC is superior to SILC in terms of short-term incisional pain. Experienced laparoscopic surgeons can perform both SILC and NSC without an increase in operative time.

Umemura|Akira|A| Suto|Takayuki|T| Nakamura|Seika|S| Fujiwara|Hisataka|H| Endo|Fumitaka|F| Nitta|Hiroyuki|H| Takahara|Takeshi|T| Sasaki|Akira|A|


The cardiovascular and hypothalamus-pituitary-adrenal axis response to stress is controlled by glucocorticoid receptor sequence variants and promoter methylation.

Abstract:
BACKGROUND
Gender, genetic makeup, and prior experience interact to determine physiological responses to an external perceived stressor. Here, we investigated the contribution of both genetic variants and promoter methylation of the NR3C1 (glucocorticoid receptor) gene to the cardiovascular and hypothalamus-pituitary-adrenal (HPA) axis response to the socially evaluated cold pressor test (seCPT).

RESULTS
Two hundred thirty-two healthy participants were recruited and underwent the experiment. They were randomly assigned to either the seCPT group (cold water) or a control group (warm water). The seCPT group had a clear stress reaction; salivary cortisol levels and peak systolic and diastolic blood pressure all increased significantly compared to the control group. GR genotype (TthIIII, NR3C1-I, 1H, E22E, R23K, BclI and 9beta) and methylation data were obtained from 218 participants. Haplotypes were built from the GR genotypes, and haplotype 2 (minor allele of BclI) carriers had a higher cortisol response to the seCPT in comparison to non-carriers (20.77 ± 13.22; 14.99 ± 8.42; p = 0.034), as well as independently of the experimental manipulation, higher baseline heart rate (72.44 ± 10.99; 68.74 ± 9.79; p = 0.022) and blood pressure (115.81 ± 10.47; 111.61 ± 10.74; p = 0.048). Average methylation levels throughout promoter 1F and 1H were low (2.76 and 1.69 %, respectively), but there was a strong correlation between individual CpGs and the distance separating them (Pearson's correlation r = 0.725, p = 3.03 × 10(-26)). Higher promoter-wide methylation levels were associated with decreased baseline blood pressure, and when incorporated into a linear mixed effect model significantly predicted lower systolic and diastolic blood pressure evolution over time in response to the experimental manipulation. The underlying genotype significantly predicted methylation levels; particularly, the homozygous BclI minor allele was associated with higher methylation in promoter 1H (p = 0.042).

CONCLUSIONS
This is one of the first studies linking epigenetic modifications of the GR promoter, receptor genotype and physiological measures of the stress response. At baseline, there were clear genetic and epigenetic effects on blood pressure. The seCPT induced a strong cardiovascular and HPA axis response, and both systems were affected by the functional genetic variants, although methylation also predicted blood pressure reactivity. The return to baseline was predominantly influenced by the genomic sequence. Overall, the physiological response to the seCPT is controlled by an exquisite mix of genetic and epigenetic factors.

Glucocorticoid receptor
Methylation
Alternative promoter
Single nucleotide polymorphism


Relations between approved platinum drugs and non-coding RNAs in mesothelioma.

Abstract: Malignant mesothelioma diseases feature an increasing risk due to their severe forms and their association with asbestos exposure. Platinum(II) complexes such as cisplatin and carboplatin are clinically approved for the therapy of mesothelioma often in combination with antimetabolites such as pemetrexed or gemcitabine. It was observed that pathogenic properties of mesothelioma cells and the response of mesothelioma tumors towards platinum-based drugs are strongly influenced by non-coding RNAs, in particular, by small microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). These non-coding RNAs controlled drug sensitivity and the development of tumor resistance towards platinum drugs. An overview of the interactions between platinum drugs and non-coding RNAs is given and the influence of non-coding RNAs on platinum drug efficacy in mesothelioma is discussed. Suitable non-coding RNA-modulating agents with potentially beneficial effects on cisplatin treatment of mesothelioma diseases are mentioned. The understanding of mesothelioma diseases concerning the interactions of non-coding RNAs and platinum drugs will optimize existing therapy schemes and pave the way to new treatment options in future.

DMPM, diffuse malignant peritoneal mesothelioma

MALAT1, metastasis-associated lung adenocarcinoma transcript 1

P P P P P M M M M M M M M M M M M M M M M M M M M M M M M M M M M M


Poverty is Not Just an Indicator: The Relationship Between Income, Poverty, and Child Well-Being.

Abstract: In this article, we review the evidence on the effects of poverty and low income on children's development and well-being. We argue that poverty is an important indicator of societal and child well-being, but that poverty is more than just an indicator. Poverty and low income are causally related to worse child development outcomes, particularly cognitive developmental and educational outcomes. Mechanisms through which poverty affects these outcomes include material hardship, family stress, parental and cognitive inputs, and the developmental context to which children are exposed. The timing, duration, and community context of poverty also appear to matter for children's outcomes-with early experiences of poverty, longer durations of poverty, and higher concentrations of poverty in the community leading to worse child outcomes.


Synthesis of Thienopyrimidine Derivatives as Inhibitors of STAT3.

Abstract: A series of thienopyrimidine compounds (6Aa-g and 6Ba-d) were synthesized and characterized by NMR spectroscopy and mass spectrometry. These compounds (6Aa-g and 6Ba-d) potently inhibited STAT3 expression induced by IL-6 in a dose-dependent manner with IC50 values of 5.73-0.32 μM. Among the prepared thienopyrimidine derivatives, 6Aa, 6Ab, 6Ba and 6Bc significantly suppressed the phosphorylation of STAT3 and ERK1/2 stimulated by IL-6 in Hep3B cells. Furthermore, the synthesized compounds might be useful remedies for the treatment of inflammatory diseases by inhibiting the action of IL-6.

Jang|Hyun-Jae|HJ|
Kim|Sung Min|SM|
Rho|Mun-Chual|MC|
Lee|Seung Woong|SW|
Song|Yang-Heon|YH|

D048049:Extracellular Signal-Regulated MAP Kinases


Markerless Escherichia coli rrn Deletion Strains for Genetic Determination of Ribosomal Binding Sites.

Abstract: Single-copy rrn strains facilitate genetic ribosomal studies in Escherichia coli. Consecutive markerless deletion of rrn operons resulted in slower growth upon inactivation of the fourth copy, which was reversed by supplying transfer RNA genes encoded in rrn operons in trans. Removal of the sixth, penultimate rrn copy led to a reduced growth rate due to limited rrn gene dosage. Whole-genome sequencing of variants of single-copy rrn strains revealed duplications of large stretches of genomic DNA. The combination of selective pressure, resulting from the decreased growth rate, and the six identical remaining scar sequences, facilitating homologous recombination events, presumably leads to elevated genomic instability.

D000900:Anti-Bacterial Agents
D001665:Binding Sites
D024881:Drug Resistance, Bacterial
D004926:Escherichia coli
D009876:Operon
D012335:RNA, Ribosomal
D012343:RNA, Transfer
D012270:Ribosomes
D017384:Sequence Deletion

ribosome
duplication
genomic instability
rrl
rrs


Diagnostic criteria of well differentiated thyroid tumor of uncertain malignant potential; a histomorphological and immunohistochemical appraisal.

Abstract:
BACKGROUND
Well differentiated thyroid tumor of uncertain malignant potential (WDT-UMP) represents a true "gray zone" of "follicular patterned" thyroid lesions, that needs to be characterized in order to outright the diagnosis of carcinoma and avoid unnecessary aggressive treatment.

AIM
To emphasize on the histomorphological criteria for more accurate diagnosis of WDT-UMP. Also to compare the immunohistochemical expression of CK19 of WDT-UMP versus adenoma and papillary thyroid carcinoma (PTC).

MATERIALS AND METHODS
The study included 60 thyroid specimens; 18 WDT-UMPs, 24 PTC (18 classic variant and 6 follicular variants) and 18 benign thyroid lesions (8 adenoma, 6 Hashimoto's thyroiditis and 4 hyperplastic nodules). H&E stained sections were assessed according to the published major and minor criteria of malignancy in the thyroid. CK 19 immunostaining was examined and evaluated according to the proportion and intensity scores.

RESULTS
We could detect the absence of nuclear inclusions, presence of characteristic nuclear groove, nuclear clearing, ovoid nuclei, nuclear crowdness, nuclear enlargement and pleomorphism as important reliable features for diagnosis of WDT-UMP with p value (<0.0001 for each). WDT-UMP showed moderate to strong CK 19 immunostaining with proportion scores 3 and 4; an intermediate expression profile; higher than adenoma and less than papillary carcinoma (p<0.0001).

CONCLUSION
The constellations of both major and minor criteria of malignancy are important clues for WDT-UMP diagnosis which could be ascertained by CK 19 immunostaining.

Yassin|Fatma El-Zahraa Salah El-Deen|Fel-Z|

Well-differentiated thyroid tumors uncertain malignant potential


Sleeping space matters: LLINs usage in Ghana.

Abstract: Long Lasting Insecticidal Net (LLIN) is an effective malaria prevention mechanism. However, ownership of LLIN does not imply its use among households. The availability of enough sleeping space is a natural prerequisite to install and use LLINs. The objective of this study was to explore the effect of sleeping space and other socio-demographic factors of households' heads on LLINs usage among households. A cross-sectional household-based study was conducted using a quantitative approach. Data was collected exclusively from households that received LLINs at no direct financial cost to them in a mass malaria campaign conducted in the study area using a structured questionnaire. A total of 383 households sampled for the study received 1,181 LLINs with a range of 1 to 15 LLINs per household. Less than 16% of households that received more than 2 LLINs installed all the LLINs they received during the distribution. Among households that received LLINs, 45% of them did not use them at all and 36% of them used them every night including the night before data collection. The number of bedrooms, children and members per household, and the number of occupants per bedroom were also found statistically associated with the use of LLINs among households. The study used a quantitative approach to investigate sleeping space in relation to LLINs usage and malaria control, an area and topic that has not been adequately covered in the literature.

Sleeping space
Usage
Ghana
Households
Malaria campaigns
Healthcare innovation adoption
Long-lasting insecticidal nets
Malaria prevention and control


The effect of luseogliflozin and alpha-glucosidase inhibitor on heart failure with preserved ejection fraction in diabetic patients: rationale and design of the MUSCAT-HF randomised controlled trial.

Abstract:
INTRODUCTION
Type 2 diabetes mellitus (T2DM) is a strong risk factor for coronary artery disease and heart failure, particularly heart failure with preserved ejection fraction (HFpEF). The aim of the ongoing MUSCAT-HF (It stands for Prospective Comparison of Luseogliflozin and Alpha-glucosidase on the Management of Diabetic Patients with Chronic Heart Failure and Preserved Ejection Fraction) trial is to evaluate the efficacy of luseogliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, versus voglibose, an alpha-glucosidase inhibitor, using brain natriuretic peptide (BNP) as the index of therapeutic effect in T2DM patients with HFpEF.

METHODS AND ANALYSIS
A total of 190 patients with T2DM and HFpEF (ejection fraction >45%) who are drug-naïve or taking any anti-diabetic agents will be randomised (1:1) to receive luseogliflozin 2.5 mg one time per day or voglibose 0.2 mg three times per day. The patients will be stratified by age (<65 years, ≥65 years), baseline haemoglobin A1c (<8.0%, ≥8.0%), baseline BNP (<100 pg/mL, ≥100 pg/mL), baseline renal function (estimated glomerular filtration rate ≥60 mL/min/1.73 m2, <60 mL/min/1.73 m2), use of thiazolidine or not and presence or absence of atrial fibrillation and flutter at screening. After randomisation, participants will receive the study drug for 12 weeks in addition to their background therapy. The primary endpoint is the proportional change in baseline BNP after 12 weeks of treatment. The key secondary endpoints are the change from baseline in the ratio of early mitral inflow velocity to mitral annular early diastolic velocity, body weight and glycaemic control after 12 weeks of treatment.

ETHICS AND DISSEMINATION
The study has been approved by the ethics committee and the patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals.

TRIAL REGISTRATION NUMBER
UMIN000018395.

Ejiri|Kentaro|K| Miyoshi|Toru|T|0000-0002-9039-3439 Nakamura|Kazufumi|K| Sakuragi|Satoru|S| Munemasa|Mitsuru|M| Namba|Seiji|S| Takaishi|Atsushi|A| Ito|Hiroshi|H|

sodium-glucose cotransporter 2 inhibitor


Novel aspects of the endocrinology of the menstrual cycle.

Abstract: Ovarian control of gonadotrophin secretion is normally achieved via the feedback mechanisms mediated by oestradiol and progesterone. Evidence has been provided that nonsteroidal substances, such as inhibin A and B, participate in the negative feedback control of FSH secretion. Another nonsteroidal ovarian substance is gonadotrophin surge-attenuating factor (GnSAF), the activity of which is particularly evident in women undergoing ovulation induction. Accumulating evidence has suggested that GnSAF plays a physiological role during the menstrual cycle. In particular, this factor antagonizes the sensitizing effect of oestradiol on the pituitary response to gonadotrophin-releasing hormone during the follicular phase of the cycle. A hypothesis has been developed that, in the late follicular phase, the activity of GnSAF is reduced and this facilitates the sensitizing effect of oestradiol on the pituitary, thus enforcing the massive discharge of gonadotrophins at the midcycle LH surge. The interaction of oestradiol, progesterone and GnSAF on the hypothalamic-pituitary system provides a novel approach to explain the mechanisms which control LH secretion during the normal menstrual cycle. The ovarian control of gonadotrophin secretion during the normal menstrual cycle is achieved via negative and positive feedback mechanisms. The steroids oestradiol and progesterone are the main regulators; however, nonsteroidal substances, such as inhibin A and inhibn B, also participate. Accumulating evidence has demonstrated that another nonsteroidal ovarian substance, gonadotrophin surge-attenuating factor (GnSAF), plays a key role in the control of LH secretion during the follicular phase and at midcycle, providing thus a novel aspect in the ovarian control of gonadotrophin secretion during the human menstrual cycle. The ovarian control of gonadotrophin secretion during the normal menstrual cycle is achieved via negative and positive feedback mechanisms. The steroids oestradiol and progesterone are the main regulators; however, nonsteroidal substances, such as inhibin A and inhibn B, also participate. Accumulating evidence has demonstrated that another nonsteroidal ovarian substance, gonadotrophin surge-attenuating factor (GnSAF), plays a key role in the control of LH secretion during the follicular phase and at midcycle, providing thus a novel aspect in the ovarian control of gonadotrophin secretion during the human menstrual cycle.

Messinis|Ioannis E|IE|
Messini|Christina I|CI|
Dafopoulos|Konstantinos|K|

gonadotrophins oestradiol progesterone inhibin GnSAF ovary


Bilateral Vein of Trolard Thrombosis.

Abstract: Isolated cortical vein thrombosis without dural sinus involvement is not common. The vein of Trolard is an important cortical vein as it drains eloquent cortex. We report 2 cases of bilateral vein of Trolard thrombosis; one with and the other without dural sinus involvement. To our knowledge, there have been no cases of bilateral vein of Trolard thrombosis reported in literature. The clinical presentation of cerebral venous thrombosis is variable; patients can present with isolated intracranial hypertension, focal neurological abnormalities, seizures, or encephalopathy.

Mishra|Sanskriti|S|
Patel|Anand V|AV|
Katz|Jeffrey M|JM|
Setton|Avi|A|
Libman|Richard B|RB|

vein of Trolard
cerebral venous thrombosis
Intracerebral hemorrhage
cortical venous thrombosis


Selective catalytic reduction of NO  with NH3: opportunities and challenges of Cu-based small-pore zeolites.

Abstract: Zeolites, as efficient and stable catalysts, are widely used in the environmental catalysis field. Typically, Cu-SSZ-13 with small-pore structure shows excellent catalytic activity for selective catalytic reduction of NO  with ammonia (NH3-SCR) as well as high hydrothermal stability. This review summarizes major advances in Cu-SSZ-13 applied to the NH3-SCR reaction, including the state of copper species, standard and fast SCR reaction mechanism, hydrothermal deactivation mechanism, poisoning resistance and synthetic methodology. The review gives a valuable summary of new insights into the matching between SCR catalyst design principles and the characteristics of Cu2+-exchanged zeolitic catalysts, highlighting the significant opportunity presented by zeolite-based catalysts. Principles for designing zeolites with excellent NH3-SCR performance and hydrothermal stability are proposed. On the basis of these principles, more hydrothermally stable Cu-AEI and Cu-LTA zeolites are elaborated as well as other alternative zeolites applied to NH3-SCR. Finally, we call attention to the challenges facing Cu-based small-pore zeolites that still need to be addressed.

Shan|Yulong|Y| Du|Jinpeng|J| Zhang|Yan|Y| Shan|Wenpo|W| Shi|Xiaoyan|X| Yu|Yunbo|Y| Zhang|Runduo|R| Meng|Xiangju|X| Xiao|Feng-Shou|FS| He|Hong|H|


Near-infrared heat lamp therapeutic effect on paraoxonase 1 and myeloperoxidase as potential biomarkers of redox state changes induced by γ-irradiation in albino rats.

Abstract: Infrared radiation has a potential therapeutic effect in some diseases. The aim of this study was to estimate the therapeutic role of near infrared heat lamp (NIRHL) on the variations of the activity of paraoxonase 1 (PON1) and myeloperoxidase (MPO), in relation to lipid disorders, associated with oxidative stress in rats gamma-irradiated. In addition, study the effect of the duration of NIRHL treatment. Animals were divided into six groups. The results revealed that irradiated rats treated with NIRHL 20 min/once/day showed positive modulation of PON1 and MPO linked to significant improvement of lipid disorders evidenced by lower triglycerides, low density lipoprotein cholesterol (LDL-C), oxidized low density lipoprotein cholesterol (oxLDL-C) and higher density lipoprotein cholesterol (HDL-C) as well as significant amelioration of redox state, manifested by markedly increase of glutathione (GSH) content, total antioxidant capacity (TAC) associated with a noticeable decrease of pro-inflammatory cytokines. (TNF-α, IL-1 beta and IL-6), nitric oxide (NO), nitric oxide synthase (NOs), malondialdehyde (MDA), compared to irradiated rats. The results showed also that the NIRHL treatment for 20 min/twice/day had negative effects on the previous parameters and on the behavior of rats such as itching, irritability, dyspnea and death in normal as well as, irradiated rats. In conclusion, the results in this study show that NIRHL therapy for a short time can effectively prevent the lipid disorders induced by radiation through the positive modulation mechanism of PON1 and MPO enzymes and improvement of oxidative stress.

Abdel-Magied|N|N|
Ahmed|A G|AG|
Shedid|S M|SM|

Paraoxonase Myeloperoxidase Rats Infrared Radiation Lipids


Association of daytime napping with prediabetes and diabetes in a Chinese population: Results from the baseline survey of the China Health and Retirement Longitudinal Study.

Abstract:
BACKGROUND
Only a few studies have investigated the effects of daytime napping on diabetes, and these studies have reported conflicting results. The aim of the present study was to examine whether daytime napping is associated with a higher risk of prediabetes and diabetes.

METHODS
The present cross-sectional study of napping duration in relation to prediabetes and diabetes was conducted in 12 277 participants. Data from the first wave (2011) of the China Health and Retirement Longitudinal Study were used. Daytime napping was divided into four groups: no napping (reference) and napping for 1-30, 31-90, and >90 min. Multinomial logistic regression was used to obtain odds ratios (ORs) and 95% confidence intervals (CIs).

RESULTS
Individuals who reported taking daily afternoon naps accounted for 53.39% of all participants. Nappers had a higher prevalence of prediabetes and diabetes than non-nappers. Compared with the reference group, the weighted fully adjusted ORs (95% CI) were 1.36 (1.10-1.68) and 1.61 (1.22-2.13) for napping >90 min in prediabetic and diabetic patients, respectively.

CONCLUSIONS
Long daytime napping duration was positively associated with prediabetes and diabetes. Further physiological and cohort studies are needed to confirm these results and elucidate potential mechanisms.

Yin|Xin|X| Liu|Qi|Q| Wei|Jiate|J| Meng|Xin|X| Jia|Chongqi|C|

prediabetes
diabetes
China
nap duration
中国
前驱糖尿病
午睡时间
糖尿病


Unexpected agency on the threshold: Asylum seekers narrating from an asylum seeker centre.

Abstract: Several studies have described the condition of asylum seekers as being on the threshold or in-between structures. Victor Turner's concept of liminality and Agamben's state of exception have been used extensively to analyse this condition, mostly to show the negative implications of the ambiguous legal (non-) status. This article argues that the condition of liminality provides an intensified doubleness of impossibility and possibility for action, which casts a different light on conceptualizing agency. Without disregarding the downside of this liminal, in-between condition, the article shows that the lack of 'normalized' connectedness to the new structure combined with physical distance from the past structure, enables reflection and feeds the power of imagination. This can lead to alternative (yet conditional) forms of agency, such as delayed agency and agency from marginal positions. Through the narratives of asylum seekers living in Dutch asylum seeker centres, the article shows the potential of transforming non-places, such as asylum seeker centres, into those in which existential meanings can emerge (even if partial). Considering these sources of agency has great implications for the short-term well-being of asylum seekers and the long-term inclusion of refugees in their countries of residence.

Ghorashi|Halleh|H|
de Boer|Marije|M|
Ten Holder|Floor|F|

Asylum seekers
in-between structures
liminality
narratives
non-places
refugees
(delayed) agency
normalized power


9th Hatter Biannual Meeting: position document on ischaemia/reperfusion injury, conditioning and the ten commandments of cardioprotection.

Abstract: In the 30 years since the original description of ischaemic preconditioning, understanding of the pathophysiology of ischaemia/reperfusion injury and concepts of cardioprotection have been revolutionised. In the same period of time, management of patients with coronary artery disease has also been transformed: coronary artery and valve surgery are now deemed routine with generally excellent outcomes, and the management of acute coronary syndromes has seen decade on decade reductions in cardiovascular mortality. Nonetheless, despite these improvements, cardiovascular disease and ischaemic heart disease in particular, remain the leading cause of death and a significant cause of long-term morbidity (with a concomitant increase in the incidence of heart failure) worldwide. The need for effective cardioprotective strategies has never been so pressing. However, despite unequivocal evidence of the existence of ischaemia/reperfusion in animal models providing a robust rationale for study in man, recent phase 3 clinical trials studying a variety of cardioprotective strategies in cardiac surgery and acute ST-elevation myocardial infarction have provided mixed results. The investigators meeting at the Hatter Cardiovascular Institute workshop describe the challenge of translating strong pre-clinical data into effective clinical intervention strategies in patients in whom effective medical therapy is already altering the pathophysiology of ischaemia/reperfusion injury-and lay out a clearly defined framework for future basic and clinical research to improve the chances of successful translation of strong pre-clinical interventions in man.

Bell|R M|RM|
Bøtker|H E|HE|
Carr|R D|RD|
Davidson|S M|SM|
Downey|J M|JM|
Dutka|D P|DP|
Heusch|G|G|
Ibanez|B|B|
Macallister|R|R|
Stoppe|C|C|
Ovize|M|M|
Redington|A|A|
Walker|J M|JM|
Yellon|D M|DM|

Ischaemia
Reperfusion
Injury
Conditioning
Ischaemic
Preconditioning
Clinical trials
Cardiac surgery
Infarction
Pre-clinical
Apoptosis
Asprin
Autophagy
Basic research
Beta blockers
CABG
Cyclosporine
DNA
Metoprolol
Mitochondrial transition pore
Necroptosis
Necrosis
Opiates
Postconditioning
Pyroptosis
RISK pathway
SAFE pathway
Statins
Valve replacement
p2y12

P P P P P P P P P P U U U R U U U U U U U U U U U U U U M U


Predicting nurse fatigue from measures of work demands.

Abstract: Fatigue arising from excessive work demands is a known safety challenge in hospital nurses. This study aimed to determine which measures of work demands during nursing work are most predictive of hospital nurse fatigue levels at the end of the work shift. Measures of work demands of registered nurses from two hospital units in the United States were collected from organizational data sources, wearable sensors, and questionnaires. Fatigue levels were measured at the start and end of each shift using the Brief Fatigue Inventory. Multilevel linear regression analysis was used to predict end of shift fatigue based on work demand variables. The best fit model included multiple variables from organizational data sources and a physical activity variable measured by a wearable sensor. Organizational data can be used to create dynamic measures of work demands as they occur and predict end of shift fatigue levels in hospital nurses.

Brzozowski|Sarah L|SL|
Cho|Hyeonmi|H|
Arsenault Knudsen|Élise N|ÉN|
Steege|Linsey M|LM|


Strategies for detecting rickettsiae and diagnosing rickettsial diseases.

Abstract: Rickettsial diseases and scrub typhus constitute a group of the oldest known vector-borne diseases. The cosmopolitan distribution of the vectors that transmit rickettsiae and orientiae leads to a worldwide prevalence of these diseases. Despite their significant historical status, detection and diagnosis of these diseases are still evolving today. Serological methods remain among the most prevalent techniques used for the detection/diagnosis of rickettsial diseases and scrub typhus. Molecular techniques have been instrumental in increasing the sensitivity/specificity of diagnosis, identifying new Rickettsia and Orientia species and have enhanced epidemiological capabilities when used in combination with serological methods. In this review, we discuss these techniques and their associated pros and cons.

Luce-Fedrow|Alison|A|
Mullins|Kristin|K|
Kostik|Alex P|AP|
St John|Heidi K|HK|
Jiang|Ju|J|
Richards|Allen L|AL|

D001431:Bacteriological Techniques
D006801:Humans
D025202:Molecular Diagnostic Techniques
D012282:Rickettsia Infections
D016996:Rickettsieae
D012612:Scrub Typhus
D012698:Serologic Tests

Rickettsia
Orientia
ELISA
multilocus sequence typing
quantitative real-time PCR
scrub typhus group
spotted fever group
typhus group


Imaging surface acoustic wave dynamics in semiconducting polymers by scanning ultrafast electron microscopy.

Abstract: Understanding the mechanical properties of organic semiconductors is essential to their electronic and photovoltaic applications. Despite a large volume of research directed toward elucidating the chemical, physical and electronic properties of these materials, little attention has been directed toward understanding their thermo-mechanical behavior. Here, we report the ultrafast imaging of surface acoustic waves (SAWs) on the surface of the Poly(3-hexylthiophene-2,5-diyl) (P3HT) thin film at the picosecond and nanosecond timescales. We then use these images to measure the propagation velocity of SAWs, which we then employ to determine the Young's modulus of P3HT. We further validate our experimental observation by performing a semi-empirical transient thermoelastic finite element analysis. Our findings demonstrate the potential of ultrafast electron microscopy to not only probe charge carrier dynamics in materials as previously reported, but also to measure their mechanical properties with great accuracy. This is particularly important when in situ characterization of stiffness for thin devices and nanomaterials is required.

Najafi|Ebrahim|E| Liao|Bolin|B| Scarborough|Timothy|T| Zewail|Ahmed|A|

Surface acoustic waves
Ultrafast electron microscopy
Mechanical properties
Organic thin films
Rayleigh waves


Amino acid supplementation is anabolic during the acute phase of endotoxin-induced inflammation: A human randomized crossover trial.

Abstract:
BACKGROUND & AIMS
Inflammation is catabolic and causes muscle loss. It is unknown if amino acid supplementation reverses these effects during the acute phase of inflammation. The aim was to test whether amino acid supplementation counteracts endotoxin-induced catabolism.

METHODS
Eight young, healthy, lean males were investigated three times in randomized order: (i) normal conditions (Placebo), (ii) endotoxemia (LPS), and (iii) endotoxemia with amino acid supplementation (LPS + A). Protein kinetics were determined using phenylalanine, tyrosine, and urea tracers. Each study day consisted of a four-hour non-insulin stimulated period and a two-hour hyperinsulinemic euglycemic clamp period. Muscle biopsies were collected once each period.

RESULTS
Endotoxin administration created a significant inflammatory response (cytokines, hormones, and vital parameters) without significant differences between LPS and LPS + A. Whole body protein breakdown was elevated during LPS compared with Placebo and LPS + A (p < 0.05). Whole body protein synthesis was higher during LPS + A than both Placebo and LPS (p < 0.003). Furthermore, protein synthesis was higher during LPS than during Placebo (p < 0.02). Net muscle phenylalanine release was markedly decreased during LPS + A (p < 0.004), even though muscle protein synthesis and breakdown rates did not differ significantly between interventions. LPS + A increased mammalian target of rapamycin (mTOR) phosphorylation (p < 0.05) and eukaryotic translation factor 4E-binding protein 1 (4EBP1) phosphorylation (p = 0.007) without activating AMPK or affecting insulin signaling through Akt. During insulin stimulation net muscle phenylalanine release and protein degradation were further reduced.

CONCLUSIONS
Amino acid supplementation in the acute phase of inflammation reduces whole body and muscle protein loss, and this effect is associated with activation of mTOR and downstream signaling to protein synthesis through mTORC1, suggesting a therapeutic role for intravenous amino acids in inflammatory states.

CLINICAL TRIAL REGISTRY
The Central Denmark Region Ethics Commitee (1-10-71-410-12) www.clinicaltrials.gov (identification number NCT01705782).

Rittig|N|N|
Bach|E|E|
Thomsen|H H|HH|
Johannsen|M|M|
Jørgensen|J O|JO|
Richelsen|B|B|
Jessen|N|N|
Møller|N|N|

D048868:Adaptor Proteins, Signal Transducing

D000076222:Mechanistic Target of Rapamycin Complex 1

Amino acids
Inflammation
mTOR
Endotoxin (lipopolysaccharide, LPS)
Tracer kinetics


The transplant cohort of the German center for infection research (DZIF Tx-Cohort): study design and baseline characteristics.

Abstract: Infectious complications are the major cause of morbidity and mortality after solid organ and stem cell transplantation. To better understand host and environmental factors associated with an increased risk of infection as well as the effect of infections on function and survival of transplanted organs, we established the DZIF Transplant Cohort, a multicentre prospective cohort study within the organizational structure of the German Center for Infection Research. At time of transplantation, heart-, kidney-, lung-, liver-, pancreas- and hematopoetic stem cell- transplanted patients are enrolled into the study. Follow-up visits are scheduled at 3, 6, 9, 12 months after transplantation, and annually thereafter; extracurricular visits are conducted in case of infectious complications. Comprehensive standard operating procedures, web-based data collection and monitoring tools as well as a state of the art biobanking concept for blood, purified PBMCs, urine, and faeces samples ensure high quality of data and biosample collection. By collecting detailed information on immunosuppressive medication, infectious complications, type of infectious agent and therapy, as well as by providing corresponding biosamples, the cohort will establish the foundation for a broad spectrum of studies in the field of infectious diseases and transplant medicine. By January 2020, baseline data and biosamples of about 1400 patients have been collected. We plan to recruit 3500 patients by 2023, and continue follow-up visits and the documentation of infectious events at least until 2025. Information about the DZIF Transplant Cohort is available at https://www.dzif.de/en/working-group/transplant-cohort .

Karch|André|A|
Schindler|Daniela|D|
Kühn-Steven|Andrea|A|
Blaser|Rainer|R|
Kuhn|Klaus A|KA|
Sandmann|Lisa|L|
Sommerer|Claudia|C|
Guba|Markus|M|
Heemann|Uwe|U|
Strohäker|Jens|J|
Glöckner|Stephan|S|
Mikolajczyk|Rafael|R|
Busch|Dirk H|DH|
Schulz|Thomas F|TF|
|||

Infection
Immunosuppression
Clinical cohort study
Organ transplantation


Large Field Alpha Irradiation Setup for Radiobiological Experiments.

Abstract: The use of alpha particles irradiation in clinical practice has gained interest in the past years, for example with the advance of radionuclide therapy. The lack of affordable and easily accessible irradiation systems to study the cell biological impact of alpha particles hampers broad investigation. Here we present a novel alpha particle irradiation set-up for uniform irradiation of cell cultures. By combining a small alpha emitting source and a computer-directed movement stage, we established a new alpha particle irradiation method allowing more advanced biological assays, including large-field local alpha particle irradiation and cell survival assays. In addition, this protocol uses cell culture on glass cover-slips which allows more advanced microscopy, such as super-resolution imaging, for in-depth analysis of the DNA damage caused by alpha particles. This novel irradiation set-up provides the possibility to perform reproducible, uniform and directed alpha particle irradiation to investigate the impact of alpha radiation on the cellular level.

Roobol|Stefan J|SJ|
Kouwenberg|Jasper J M|JJM|
Denkova|Antonia G|AG|
Kanaar|Roland|R|
Essers|Jeroen|J|

irradiation
alpha particle
microscopy
DNA damage
53BP1
DSB
FNTD
clonogenic survival
dosimetry
external irradiation


Design and synthesis of zinc protoporphyrin IX-adamantane/cyclodextrin/cellulose nanocrystals complexes for anticancer photodynamic therapy.

Abstract: Two protoporphyrin IX (PpIX) adamantane derivatives were synthesized and then metallated with zinc. The Zn-PpIX derivatives, exhibiting a high singlet oxygen quantum yield, were tested for their photodynamic activity against the HT-29 cell line. In order to enhance their water-solubility and their cellular bioavailability, these photosensitizers were encapsulated into the hydrophobic cavity of cyclodextrins (CD) previously attached to cellulose nanocrystals (CNCs) via electrostatic interactions. Under illumination, the encapsulated adamantanyl-porphyrins exerted an enhanced in vitro cytotoxicity, as compared with the corresponding free photosensitizers.

Ndong Ntoutoume|Gautier M A|GMA|
Granet|Robert|R|
Mbakidi|Jean-Pierre|JP|
Constantin|Eléna|E|
Bretin|Ludovic|L|
Léger|David Y|DY|
Liagre|Bertrand|B|
Chaleix|Vincent|V|
Brégier|Frédérique|F|
Sol|Vincent|V|

D004354:Drug Screening Assays, Antitumor

Cellulose nanocrystals
Photodynamic therapy
Colorectal cancer
Nanoparticles
Porphyrins


Development of a chicken-derived antivenom against the taipan snake (Oxyuranus scutellatus) venom and comparison with an equine antivenom.

Abstract: A chicken-derived antivenom (ChDAv) towards taipan snake (Oxyuranus scutellatus) venom was produced by purifying anti-taipan IgY from egg yolks of hens immunized with taipan venom. The productivity, antivenomic profile, neutralization ability, pharmacokinetic properties and immunogenicity of the ChDAv were compared with those of an antivenom produced in horses (EDAv). We found that 382 eggs are required to produce the mass of anti-taipan antibodies contained in one liter of equine hyperimmune plasma, and that 63 chickens would be needed to generate the amount of anti-taipan antibodies annually produced by one horse. It was estimated that, in Costa Rica, the production of anti-taipan antibodies could be 40% cheaper if chickens were used as immunoglobulin source, instead of horses. During antivenomic assessment, ChDAv showed lower ability to immunocapture the α subunit of taipoxin, the most important neurotoxin in the venom. ChDAv showed a lower ability to neutralize the coagulant and lethal activities of taipan venom. ChDAv was more immunogenic in rabbits than EDAv, probably due to the fact that chickens are phylogenetically more distant to rabbits than horses. This finding may explain why clearance from rabbit bloodstream was faster for chicken-IgY than for equine-IgG in a pharmacokinetic study. In conclusion, the production of anti-taipan antivenom was less effective when chicken egg yolks were used as source of immunoglobulins instead of horses.

Navarro|Diego|D|
Vargas|Mariángela|M|
Herrera|María|M|
Segura|Álvaro|Á|
Gómez|Aarón|A|
Villalta|Mauren|M|
Ramírez|Nils|N|
Williams|David|D|
Gutiérrez|José María|JM|
León|Guillermo|G|

Antivenom
Oxyuranus scutellatus
Pharmacokinetics
Antibody response
Foreignness
Snake venom


Antibiotic fidaxomicin is an RdRp inhibitor as a potential new therapeutic agent against Zika virus.

Abstract:
BACKGROUND
Zika virus (ZIKV) infection is a global health problem, and its complications, including congenital Zika syndrome and Guillain-Barré syndrome, constitute a continued threat to humans. Unfortunately, effective therapeutics against ZIKV infection are not available thus far.

METHODS
We screened the compounds collection consisting of 1789 FDA-approved drugs by a computational docking method to obtain anti-ZIKV candidate compounds targeting ZIKV RNA-dependent RNA polymerase (RdRp). SPR (BIAcore) assay was employed to demonstrate the candidate compounds' direct binding to ZIKV RdRp, and polymerase activity assay was used to determine the inhibitory effect on ZIKV RdRp-catalyzed RNA synthesis. The antiviral effects on ZIKV in vitro and in vivo were detected in infected cultured cells and in Ifnar1-/- mice infected by ZIKV virus using plaque assay, western blotting, tissue immunofluorescence, and immunohistochemistry.

RESULTS
Here, we report that a first-in-class macrocyclic antibiotic, which has been clinically used to treat Clostridium difficile infection, fidaxomicin, potently inhibits ZIKV replication in vitro and in vivo. Our data showed that fidaxomicin was effective against African and Asian lineage ZIKV in a wide variety of cell lines of various tissue origins, and prominently suppressed ZIKV infection and significantly improved survival of infected mice. In addition, fidaxomicin treatment reduced the virus load in the brains and testes, and alleviated ZIKV-associated pathological damages, such as paralysis, hunching, and neuronal necrosis in the cerebra. Furthermore, our mechanistic study showed that fidaxomicin directly bound ZIKV NS5 protein and inhibited the RNA synthesis-catalyzing activity of ZIKV RdRp.

CONCLUSIONS
Our data suggest that fidaxomicin may represent an effective anti-ZIKV agent. In the light that fidaxomicin is already a clinically used drug, there might be a promising prospect in the development of fidaxomicin to be an antiviral therapeutic.

Yuan|Jie|J| Yu|Jianchen|J| Huang|Yun|Y| He|Zhenjian|Z| Luo|Jia|J| Wu|Yun|Y| Zheng|Yingchun|Y| Wu|Jueheng|J| Zhu|Xun|X| Wang|Haihe|H| Li|Mengfeng|M|

D061307:Human Umbilical Vein Endothelial Cells

Fidaxomicin
RdRp inhibitor
Zika virus
Antiviral
NS5


Parental Corporal Punishment and Child Temperament: Independent and Interactive Predictors of Child Emotion Regulation in China.

Abstract: The goal of this study was to simultaneously examine the independent and interactive effects of paternal and maternal corporal punishment, and child temperament on child emotion regulation over time in China. These links were assessed on a longitudinal study of 619 father-mother dyads and their children in primary schools (data collected in 2011 and 2014). Results showed an additive model where both parental corporal punishment and child temperament independently predicted child emotion regulation 3 years later. In addition, the effects of parental corporal punishment exhibited gender differences, with paternal corporal punishment predicting girls' emotion regulation and both paternal and maternal corporal punishment predicting boys' emotion regulation 3 years later. Moreover, the interactive effects of paternal and maternal corporal punishment and temperament on child emotion regulation were not found in the present study. These findings point to the importance of examining multiple factors within the family system to further understand the developmental process of child emotion regulation, particularly within the Chinese cultural context.

Wang|Meifang|M| Wang|Yuzhu|Y| Wang|Fang|F| Xing|Xiaopei|X|

corporal punishment
temperament
emotion regulation
longitudinal study


Calibrated automated thrombography for monitoring coagulation function in patients with intracerebral haemorrhage.

Abstract:
OBJECTIVE
To monitor coagulation function in patients with intracerebral haemorrhage (ICH) using calibrated automated thrombography.

METHODS
Patients admitted to hospital with ICH (confirmed within 18 h of symptom onset) were enrolled. Patient history and blood samples were obtained within 6 h of admission; further blood samples were collected on days 4, 8 and 15 (or on discharge between days 9-15: grouped with day 15 data). Blood samples were also collected from age- and sex-matched healthy controls. All samples underwent calibrated automated thrombography.

RESULTS
At admission, thrombin lag time and time to peak was longer, and endogenous thrombin potential and peak height were lower, in patients with ICH (n = 20) than in healthy controls (n = 29). Lag time in patients with ICH gradually decreased, but remained significantly longer than in controls until day 8. Time to peak also gradually decreased, but remained longer in patients than in controls by day 15. Endogenous thrombin potential and peak height gradually increased in patients, but remained lower than in controls on day 15.

CONCLUSIONS
Patients with ICH have poorer coagulation function than healthy individuals, but this function gradually recovers during hospitalization.

Yu|Yao|Y| Wu|Jun|J| Zhao|Wei|W| Zhao|Lei|L| Zhu|Chunpeng|C| Gao|Xuguang|X|

Intracerebral haemorrhage
thrombin
calibrated automated thrombogram


CO2 Methanation via Amino Alcohol Relay Molecules Employing a Ruthenium Nanoparticle/Metal Organic Framework Catalyst.

Abstract: Methanation of carbon dioxide (CO2 ) is attractive within the context of a renewable energy refinery. Herein, we report an indirect methanation method that harnesses amino alcohols as relay molecules in combination with a catalyst comprising ruthenium nanoparticles (NPs) immobilized on a Lewis acidic and robust metal-organic framework (MOF). The Ru NPs are well dispersed on the surface of the MOF crystals and have a narrow size distribution. The catalyst efficiently transforms amino alcohols to oxazolidinones (upon reaction with CO2 ) and then to methane (upon reaction with hydrogen), simultaneously regenerating the amino alcohol relay molecule. This protocol provides a sustainable, indirect way for CO2 methanation as the process can be repeated multiple times.

metal-organic frameworks
CO2 chemistry
green chemistry
sustainable chemistry


The impact of social isolation on HPA axis function, anxiety-like behaviors, and ethanol drinking.

Abstract: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is often observed in alcoholics and humans subjected to early life stress, and animal models of ethanol (EtOH) dependence. We examined HPA axis function in a rodent model of early life stress that engenders increases in behavioral and neurobiological risk factors of alcoholism. Long-Evans male rats were group housed (GH) or socially isolated (SI) for 6 weeks during adolescence. We examined the corticosterone (CORT) response to stress with and without dexamethasone (DEX) and anxiety-like behaviors. Following the DEX suppression test and behavioral assays, half of the cohort engaged in 6 weeks of EtOH drinking in a homecage, two-bottle choice intermittent access model. A subset of the cohort was not exposed to EtOH, but was used for electrophysiological measurement of glutamatergic synaptic plasticity in the basolateral amygdala (BLA). Correlational analyses examined relationships between measures of CORT, anxiety-like behaviors, and EtOH intake/preference. With DEX pre-treatment, SI rats failed to suppress CORT in response to an acute stress; GH rats showed a significant suppression. In SI rats, there was a significant negative correlation between baseline CORT and elevated plus maze open arm time, as well as significant positive correlations between baseline CORT and both EtOH intake and preference. No significant relationships between baseline CORT and behavioral measures were observed in GH rats. Glutamatergic plasticity in the BLA was similar in magnitude between GH and SI rats, and was not altered by exogenous application of CORT. These data suggest that HPA axis function is affected by SI, and this is related to antecedent anxiety-like behavior and may predispose for future EtOH self-administration. Relationships between HPA axis function, anxiety, and EtOH measures in SI rats further strengthens the utility of this paradigm in modeling vulnerability for affective disorders and alcoholism.

Butler|Tracy R|TR|
Ariwodola|Olusegun J|OJ|
Weiner|Jeffrey L|JL|

social isolation
alcoholism
stress
dependence
basolateral amygdala
hypothalamic–pituitary–adrenal axis


Modified duct-to-mucosa versus conventional pancreaticoenterostomy for pancreaticoduodenectomy: a retrospective cohort study based on propensity score matching analysis.

Abstract:
BACKGROUND
Clinically relevant postoperative pancreatic fistula (CR-POPF) remains the most common neopathy after pancreatoduodenectomy (PD). An ideal pancreaticoenterostomy (PE) which can effectively reduce the incidence of CR-POPF and its potential neopathy is needed. We aimed to assess the efficacy of our modified duct-to-mucosa PE in the PD.

METHOD
From January 2011 to December 2017, 233 consecutive patients with PD were retrospectively included from Shenzhen People's Hospital. After propensity score matching (PSM), there were 82 patients in both the modified duct-to-mucosa PE group (group A) and the conventional end-to-side inserting PE group (group B), respectively. The clinical course and the incidence of postoperative neopathy were compared between groups. Logistic regression method was utilized to analyze the association between PE approach and CR-POPF.

RESULTS
The PE time was shorter in group A (9.3 ± 1.8 min vs. 21.5 ± 2.8 min, P < 0.001). The group A had significantly lower incidence of severe neopathy (Clavien-Dindo grade > II) [7.3% (5/82) vs. 17.1% (14/82), P = 0.028] and incidence of CR-POPF [1.2% (1/82) vs. 19.5% (12/82), P < 0.001] than the group B. Our modified duct-to-mucosa PE technique was associated with a reduced risk for CR-POPF (OR, 0.11 [95% CI, 0.02-0.57]; P = 0.009) as compared with the conventional end-to-side inserting PE.

CONCLUSION
Compared with conventional end-to-side inserting PE, our modified duct-to-mucosa PE technique can effectively reduce the incidences of postoperative neopathy and CR-POPF.

TRIAL REGISTRATION
Researchregistry3877 . Registered 24 March 2018. Retrospectively registered.

Pancreaticoenterostomy
Pancreaticoduodenectomy
Postoperative pancreatic fistula


Effects of excitation light intensity on parathyroid autofluorescence with a novel near-infrared fluorescence imaging system: two surgical case reports.

Abstract: The intraoperative identification and preservation of the parathyroid glands are vital techniques, which are largely dependent on a surgeon's experience. Therefore, a simple and reproducible technique to identify the parathyroid glands during surgery is needed. Parathyroid tissue shows near-infrared (NIR) autofluorescence, which enables the intraoperative identification of the parathyroid gland. We herein present two cases that underwent surgery on the parathyroid glands, which were observed using the NIR fluorescence imaging system LIGHTVISION® (Shimazu, Kyoto, Japan). In a case of papillary thyroid carcinoma, the system was adopted to preserve normal parathyroid glands during left hemithyroidectomy. The left lower parathyroid gland was identified using the imaging system under white light; however, its autofluorescence was visualized more clearly with the excitation light of NIR. In a case of primary hyperparathyroidism due to MEN1, the system was adopted to identify and remove all of the parathyroid glands during total parathyroidectomy. The autofluorescence of diseased glands was weaker than that of normal glands, even with the excitation light of NIR. When the parathyroid glands were irradiated with a red laser pointer, the intensity of autofluorescence significantly increased. However, the largest gland, which was pathologically proven to contain strongly proliferating chief cells, did not show autofluorescence. These results suggest that normal or less diseased parathyroid glands, which are generally small and difficult to identify during surgery, showed relatively strong autofluorescence. A stronger excitation light increases the autofluorescence of parathyroid glands, which enhances sensitivity for detecting parathyroid glands during surgery. In conclusion, LIGHTVISION® is a useful device to identify parathyroid glands and an additional excitation light of a red laser pointer increases the detection sensitivity.

Aoyama|Mariko|M| Takizawa|Hiromitsu|H| Yamamoto|Kiyoshige|K| Inui|Tomohiro|T| Miyamoto|Naoki|N| Sakamoto|Shinichi|S| Kobayashi|Tomoko|T| Uehara|Hisanori|H| Tangoku|Akira|A|

Autofluorescence
near-infrared
parathyroid gland
surgery


Scrotal hematoma following femoral artery puncture.

Abstract: The scrotum hematoma following femoral artery puncture is a rare complication. The bleeding from the puncture site drained through the inguinal canal into the scrotum. The present case may indicate the importance of quick observation of the scrotum, when the puncture of femoral artery was performed.

Ishibashi|Shun|S| Sakakura|Kenichi|K|0000-0003-3566-0394 Yamamoto|Kei|K| Okochi|Tomohisa|T| Momomura|Shin-Ichi|SI| Fujita|Hideo|H|

hematoma
femoral artery puncture
complications
inguinal canal


A MOOC About Bariatric Surgery Improves Knowledge and Promotes Patients' Soft Skills.

Abstract: The ASMBS recommends that patients should be provided with educational materials to improve informed consent about bariatric surgery. Massive online open courses (MOOCs) are learning sources which are free, online, and available to people in remote situations. A French language MOOC regarding preparation for obesity surgery targets patients, as well as HCP, and people curious about this treatment. The patients' knowledge and skills after completion of the 5-week learning sessions (evaluated with semi-direct interviews) improved. Soft skills such as feeling empowered to ask questions to their HCP and explaining their plan to their relatives improved. This study suggests that MOOC can be a resource to improve knowledge and soft skills in patients for a better consent to surgery and follow-up.

Education
Informed consent
Massive online open course
Obesity surgery


Detection of Executive Performance Profiles Using the ENFEN Battery in Children Diagnosed With Attention-Deficit Hyperactivity Disorder.

Abstract: Attention-deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders in children and adolescents. People who have this disorder are characterized by presenting difficulties in the processes of sustained attention, being very active, and having poor control of their impulses. Despite the high prevalence of this disorder and the existence of various tests used for its diagnosis, few data are available regarding the usefulness and diagnostic validity of these tools. Given the difficulties that these subjects present in executive functions, the aim of this study was to evaluate whether the Neuropsychological Assessment of Executive Functions battery for Children (ENFEN, for its acronym in Spanish, Portellano et al., 2009) allows to establish specific profiles of executive performance for people with attention-deficit hyperactivity disorder (ADHD). The sample was made up of 197 participants of both sexes, aged between 6 and 12 years age (134 with a clinical diagnosis and 63 without pathology). A nonexperimental design was followed, using a comparative descriptive study method. The results indicated that the scales of phonological fluency, color path, rings, and interference are the most associated with the diagnosis of ADHD, providing data on inhibition, mental flexibility, sustained and selective attention, planning, verbal fluency, and working memory, among others. The practical implication of these results is in line with providing support in the clinical diagnosis that is carried out in children's mental health units. In addition, the ENFEN tool can be valued as a suitable psychometric instrument in the psychoeducational field, helping professionals in a school environment to be more aware of the areas of cognitive development in which a student diagnosed with ADHD will have more difficulties and, in doing so, providing more adjusted and effective psychopedagogical measures when it comes to supporting students in their adaptation to the school environment.

Navarro-Soria|Ignasi|I|
Juárez-Ruiz de Mier|Rocío|R|
García-Fernández|José Manuel|JM|
González-Gómez|Carlota|C|
Real-Fernández|Marta|M|
Sánchez-Múñoz de León|Marta|M|
Lavigne-Cervan|Rocío|R|

ENFEN
ADHD
executive function
ADHD rating scale
WISC-IV


A Rare Case of Joint Infection due to Raoultella planticola.

Abstract: Raoultella planticola , a gram-negative bacterium, first emerged in late 1900s as Klebsiella planticola . It was later classified as Raoultella genus in 2001. This nonmotile rod is usually found in soil and aquatic environment. There are two known species of Raoultella : R. planticola and R. ornithinolytica . They are responsible for numerous yet rare infections including cystitis, pneumonia, and bacteremia. To date, only one case of joint or bone infection due to R. planticola has been reported. The infection is eradicated after arthroscopic lavage and antibiotic therapy with fluoroquinolones. We present the first case of septic arthritis due to R. planticola involving a native knee joint following synovectomy during arthroscopy.


Family History is Important to Identify Patients with Monogenic Causes of Adult-Onset Chronic Kidney Disease.

Abstract: Monogenic causes of chronic kidney disease (CKD) are more prevalent in adults than previously thought, as causative gene variants are found in almost 10% of unselected patients with CKD. Even so, genetic testing in patients with adult-onset CKD is uncommon in clinical practice and the optimal criteria for patient selection remain unclear. A family history of kidney disease emerges as one marker associated with a high diagnostic yield of genetic testing. We present 3 cases of adult-onset CKD with underlying monogenic causes exemplifying different modes of inheritance. Case 1 is a 60-year-old male with slowly progressive CKD initially ascribed to hypertension and diabetes despite a family history with several affected first-degree relatives. A pathogenic MUC1 variant was found, and thus we identified the first Danish family of MUC1-associated autosomal dominant tubulointerstitial kidney disease. Case 2 is a 40-year-old female with nephrocalcinosis, nephrolithiasis, and unexplainable hypercalcemia consistent with vitamin D intoxication. The family history indicated autosomal recessive inheritance, and genetic testing revealed 2 pathogenic CYP24A1 variants in compound heterozygous form associated with idiopathic infantile hypercalcemia. Case 3 is a 50-year-old male with microscopic hematuria, proteinuria, and hearing loss. Electron microscopy of renal biopsy showed thin basal membrane syndrome, and the family history indicated X-linked inheritance. A novel missense variant in COL4A5 was identified, suggesting an atypical late-onset form of X-linked Alport syndrome. This case series illustrates the heterogeneous presentations of monogenic kidney disease in adults and emphasizes the importance of family history for initiating genetic testing to identify underlying monogenic causation. Moreover, we discuss the potential impact of genetic diagnostics on patient management and genetic family counseling.

Granhøj|Jeff|J|
Tougaard|Birgitte|B|
Lildballe|Dorte L|DL|
Rasmussen|Maria|M|

Autosomal dominant tubulointerstitial kidney disease-MUC1


Review of X-ray and computed tomography scan findings with a promising role of point of care ultrasound in COVID-19 pandemic.

Abstract: As healthcare professionals continue to combat the coronavirus disease 2019 (COVID-19) infection worldwide, there is an increasing interest in the role of imaging and the relevance of various modalities. Since imaging not only helps assess the disease at the time of diagnosis but also aids evaluation of response to management, it is critical to examine the role of different modalities currently in use, such as baseline X-rays and computed tomography scans carefully. In this article, we will draw attention to the critical findings for the radiologist. Further, we will look at point of care ultrasound, an increasingly a popular tool in diagnostic medicine, as a component of COVID-19 management.

Gandhi|Darshan|D| Ahuja|Kriti|K| Grover|Hemal|H| Sharma|Pranav|P| Solanki|Shantanu|S| Gupta|Nishant|N| Patel|Love|L|

X-ray
Computed tomography
Point of care ultrasound
COVID-19
Coronavirus
Wuhan


Lanthanum carbonate to control plasma and urinary oxalate level in type 1 primary hyperoxaluria?

Abstract:
Introduction
The therapy to reduce urinary oxalate excretion in primary hyperoxaluria type 1 is still required.

Case presentation
A 37-year-old hemodialyzed man suffered from systemic oxalosis secondary to primary hyperoxaluria type 1 exhibited a drastic plasma oxalate decrease from 110 to 22 µmol/L two months after adjunction of lanthanum carbonate to classical treatment (intensive hemodialysis with pyridoxine). A 34-year-old woman with normal kidney function presented 10 years of bilateral kidney stones due to primary hyperoxaluria type 1 [hyperoxaluria (109.2 mg/24 h), plasma oxalate (56.0 µmol/L)]. The oxalate level remained uncontrolled despite of low oxalate-normal calcium diet, pyridoxine and increased water intake though the lanthanum carbonate adjunction resulted in significant decrease in plasma oxalate and oxaluria.

Conclusion
We report the lanthanum efficacy in reducing circulating and urinary oxalate levels in type 1 primary hyperoxaluria. Possible mechanism of observed falls in oxalate concentration would be a decrease in the intestinal absorption of oxalate.

lanthanum carbonate
oxalate
primary hyperoxaluria type 1
kidney stones
nephrocalcinosis