Association of preoperative total lymphocyte count with prognosis in resected left-sided pancreatic cancer.

Abstract:
BACKGROUND
Immunologic factors such as neutrophil-lymphocyte ratio and platelet-lymphocyte ratio play an important role in predicting the oncologic outcome of patients in pancreatic ductal adenocarcinoma (PDAC). It is hypothesized that host immunity represented by total lymphocyte count at diagnostic stage would influence oncologic outcome in left-sided PDAC.

METHODS
Between January 1992 and August 2017, total of 112 patients who underwent distal pancreatectomy for left-sided PDAC were included and analysed.

RESULTS
At the time of the diagnosis, total lymphocyte count at diagnosis of left-sided PDAC was 1.8 ± 0.7 103 /μL (mean value ± standard deviation). Among different cut-off values, 1.7 showed most powerful significant differences in long-term oncologic outcomes. The patients with preoperative lymphocyte count (≤1.7) was associated with early recurrence (median 8.4 months versus 18.1 months, P = 0.011) and shorter survival (median 18.6 months versus 35.9 months, P = 0.028). Patients with preoperative total lymphocyte count over 1.7 showed higher white blood cell count (P < 0.001), platelet count (P = 0.039), neutrophil count (P = 0.004) and monocyte count (P = 0.001). However, more interestingly, neutrophil-lymphocyte ratio (P < 0.001) and platelet-lymphocyte ratio (P < 0.001) were found to be significantly higher in those with total lymphocyte count less than 1.7. Lymphocyte to monocyte ratio was inversely related to preoperative total lymphocyte count (P < 0.001). Only age was identified to be significantly different (P = 0.007). However, other clinicopathological parameters generally known to be related to tumour aggressiveness, were not different between two groups.

CONCLUSION
In conclusion, preoperative total lymphocyte at diagnostic stage is simple, and good prognostic factor in left-sided pancreatic cancer.

Rho|Seoung Yoon|SY|0000-0002-1265-826X
Hwang|Ho Kyoung|HK|
Chong|Jae Uk|JU|
Yoon|Dong Sup|DS|
Lee|Woo Jung|WJ|
Kang|Chang Moo|CM|

total lymphocyte count
left-sided pancreatic cancer
pancreatic cancer
neutrophil-lymphocyte ratio
platelet-lymphocyte ratio


Microalgae hydrothermal liquefaction and derived biocrude upgrading with modified SBA-15 catalysts.

Abstract: In this study, a novel route was proposed for microalgae biofuel production by catalytic upgrading of Chlorella hydrothermal liquefaction (HTL) derived biocrude. Al-SBA-15, CuO/Al-SBA-15, ZuO/Al-SBA-15, and CuO-ZnO/Al-SBA-15 catalysts were synthesized in a facile, one-pot way, and tested for methyl palmitate decarboxylation and biocrude upgrading without H2 addition. These modified SBA-15 catalysts enhanced alkane selectivity of methyl palmitate decarboxylation from 7.6 wt% up to 79.6 wt% at 340-350 °C. FT-IR, TG and GC-MS characterizations were employed to identify the composition and properties of the upgraded bio-oils. Compared with thermal upgrading, modified SBA-15 catalysts enriched the yield of low boiling point compounds, and the content of heavy bio-oil (>400 °C) declined from 9.57 wt% to 1.89 wt%. Hydrocarbon yield was greatly enriched on the catalysts, and aromatics predominant on Al-SBA-15 while aliphatics abundant on metal oxide(s) supported catalysts. The hydrocarbon yield was increased from 25.1 wt% (thermal) to 65.7 wt% on the CuO/Al-SBA-15.

Li|Jing|J| Fang|Xudong|X| Bian|Junjie|J| Guo|Yuehong|Y| Li|Chunhu|C|

D017550:Spectroscopy, Fourier Transform Infrared

Hydrothermal liquefaction
SBA-15 catalyst
Methyl palmitate decarboxylation
Hydrocarbon yield
Bio-oil upgrading


Identification of warm temperature acclimation-associated 65-kDa protein-2 in Kumgang fat minnow Rhynchocypris kumgangensis.

Abstract: Warm temperature acclimation-associated 65-kDa protein (Wap65) is known to respond to elevated water temperatures and the corresponding gene from several fish species has been cloned. Expression of Wap65 gene is induced by various physiological stresses, such as increase in water temperature, immune response and heavy metal exposure. Two isolated Wap65 genes, Wap65-1 and Wap65-2, display distinct tissue distribution and physiological functions despite high sequence homology. In a previous study, we identified the Wap65-1 gene (kmWap65-1) from Kumgang fat minnow, Rhynchocypris kumgangensis, a small freshwater fish endemic to Korea. The kmWap65-1 gene showed sequence homology with teleost Wap65-1 and mammalian hemopexin, and was highly expressed in response to increased water temperature and bacterial lipopolysaccharide (LPS) exposure. Here, we isolated kmWap65-2 from liver tissue of Kumgang fat minnow and compared the expression profiles of both kmWap65 genes following exposure to various physiological stresses, including thermal changes, bacterial challenge, and environmental toxins. Notably, while kmWap65-1 expression was significantly increased in response to high water temperature, LPS, cadmium, and iron, kmWap65-2 displayed no alterations in expression at high water temperature. However, kmWap65-2 expression was upregulated slightly in response to LPS and highly in presence of copper, bisphenol A, and estradiol. Based on the collective findings, we propose that kmWap65-1 and kmWap65-2 are multifunctional proteins with distinct functions that could serve as useful biomarkers for assessing physiological stress and associated responses in Kumgang fat minnow.


Sweet and Salty: Diabetic Ketoacidosis in a Patient With Nephrogenic Diabetes Insipidus.

Abstract: The co-existence of nephrogenic diabetes insipidus (NDI) with diabetes mellitus (DM) in a patient that presents in diabetic ketoacidosis (DKA) is rare and, to our knowledge, has not been described even in case reports. We report the case of a 16-year-old male with known NDI who presented to the pediatric emergency department (ED) for one day with generalized weakness and decreased appetite, found to be in moderate DKA from new-onset DM. The initial management of his dehydration and hyperosmolar state presented a unique challenge. Fluid resuscitation with isotonic fluids in a patient with NDI poses a risk of worsening hypernatremia, which can lead to seizures and death. However, the use of hypotonic fluids has the potential to lower serum osmolality too quickly, which can result in cerebral edema. Nephrology, endocrinology, and the pediatric intensive care unit (PICU) consultants were notified of this patient, and a discussion was coordinated between sub-specialists to determine the appropriate fluid resuscitation. The patient was allowed to drink free water in addition to receiving intravenous fluids (IVF) of dextrose 5% with 0.2% sodium chloride at a rate of one-and-a-half maintenance (150 mL/hr) in the ED prior to transfer to the PICU where insulin infusion was initiated. This case report provides guidance to inpatient providers on the management of patients with co-existent NDI and DM in DKA, a rare combination that requires thoughtful and urgent management.

De Sa|Hong A|HA|
Chung|Sunhee|S|
Shaniuk|Paul M|PM|

nephrogenic diabetes insipidus
diabetic ketoacidosis (dka)
adolescent diabetes
diabetes mellitus type 2


Hypocalcaemia and permanent hypoparathyroidism after total/bilateral thyroidectomy in the BAETS Registry.

Abstract: The UK Registry of Endocrine and Thyroid Surgeons (UKRETS) has been operated by the British Association of Endocrine and Thyroid Surgeons (BAETS) and Dendrite Clinical Systems Ltd. in a web-based electronic format since 2004. Data on over 90,000 endocrine procedures have been collected to date. Analysis of those cases undergoing bilateral thyroid resections in the interval July 2010 to June 2015 demonstrates that hypocalcaemia remains the commonest complication of thyroid surgery. After first-time total thyroidectomy, 23.6% of patients develop hypocalcaemia, defined as a serum calcium <2.10 mmol/L (or <1.20 mmol/L ionized calcium) on the first post-operative day. Most require treatment with calcium +/- vitamin D supplements, with around 38% of all patients being treated by the time of discharge from the index admission. By 6 months post-operative, 7.3% of patients remain on calcium/vitamin D supplements, reflecting persistent (though not necessarily permanent) hypoparathyroidism. Risk factors for persistent hypocalcaemia are principally concomitant level VI lymph node dissection [odds ratio (OR) =2.73]; re-operative surgery (OR =1.44); and inter-surgeon variation.


Role of CT-guided transthoracic biopsy in the diagnosis of mycobacterial infection.

Abstract: Mycobacterial infection(MI) is sometimes diagnosed using CT-guided transthoracic needle biopsy (TNB). However, the exact role of CT-guided TNB in this diagnostic process is not clearly known. The purpose of this study is to analyze the role of CT-guided TNB in patients with MI who present with a focal lung lesion. Of 1233 patients who underwent CT-guided TNB from January 2010 through February 2016 at our institution, patients with a final diagnosis of MI were included for analysis. Clinical characteristics and biopsy-related factors were compared between patients whose diagnosis could be established using TNB samples alone (group 1) and those whose samples from additional tests were necessary for diagnosis (group 2). We also analyzed the possible benefit of CT-guided TNB as compared with bronchoscopy in a subgroup who underwent both procedures. 47 patients with MI were included in the study, with 37 patients (78.7%) in group 1 and 10 patients (21.2%) in group 2. There was no statistically significant difference in clinical characteristics or biopsy-related factors between the two groups. Of 41 patients with MI who underwent both bronchoscopy and TNB, success in diagnosis was solely attributable to TNB in 16 (39.0%) patients; in 19 (46.0%) patients, diagnosis could be made based on bronchoscopy results alone. MI can be successfully diagnosed by CT-guided TNB in about 80% of patients with MI who underwent TNB, but 46% of the patients could have been diagnosed with bronchoscopy results alone. CT-guided TNB is inferior to bronchoscopy in the differentiation of Mycobacterium species even in peripheral lung lesions.


Metabolism of a serotonin-4 receptor partial agonist 4-{4-[4-tetrahydrofuran-3-yloxy)-benzo[d]isoxazol-3-yloxymethyl]-piperidin-1-ylmethyl}-tetrahydropyran-4-ol (TBPT): identification of an unusual pharmacologically active cyclized oxazolidine metabolite in human.

Abstract: 4-{4-[4-Tetrahydrofuran-3-yloxy)-benzo[d]isoxazol-3-yloxymethyl]-piperidin-1-ylmethyl}-tetrahydropyran-4-ol (PF-4995274, TBPT) is a new agent that is a partial agonist of the human serotonin-4 (5-HT4) receptor and is under investigation for neurological disorders. Metabolism of TBPT was examined in vitro in human liver microsomes and human hepatocytes. Metabolites were also identified in the plasma of healthy human subjects in a phase 1 clinical study. Human-derived metabolite profiles were compared with corresponding profiles obtained in laboratory animal species. There were two major routes of metabolism in vitro: N-dealkylation of the methyltetrahydropyran moiety (M1) and hydroxylation at the seven position of the benzisoxazole moiety (M4). These were also observed in human plasma; however, in that matrix, the major metabolite was an unusual cyclized oxazolidine entity (M2). M2 was proposed to be formed via generation of an intermediate 4° iminium ion on the piperidine ring followed by spontaneous cyclization by attack of the β-hydroxyl substituent of the tetrahydropyran ring to form a cyclized oxazolidine product. An authentic standard of the metabolite was generated using a methylene-blue-sensitized photochemical oxidation reaction as well as microbial transformation. Further investigation of this metabolite showed that it also possessed 5-HT4 agonism activity similar to the parent. The metabolite was 150-fold more highly protein bound in human plasma than TBPT, which is consistent with its presence as a major circulating metabolite while being only a minor metabolite in in vitro systems. Overall, this illustrates the importance of understanding the complex dispositional properties of a pharmacologically active metabolite.

Sawant-Basak|Aarti|A|
Coffman|Karen J|KJ|
Walker|Gregory S|GS|
Ryder|Tim F|TF|
Tseng|Elaine|E|
Miller|Emily|E|
Lee|Carlos|C|
Vanase-Frawley|Michelle A|MA|
Wong|John W|JW|
Brodney|Michael A|MA|
Rapp|Tracey|T|
Obach|R Scott|RS|

D058828:Serotonin 5-HT4 Receptor Agonists

metabolism
microsomes
hepatic metabolism
mass spectrometry
protein binding


Pedicle screw-based posterior dynamic stabilizers for degenerative spine: in vitro biomechanical testing and clinical outcomes.

Abstract: Dynamic stabilization in a degenerate symptomatic spine may be advantageous compared with conventional fusion procedures, as it helps preserve motion and minimizes redistribution of loads at instrumented and adjacent segments. This article presents a systematic review of biomechanical and clinical evidence available on some of the pedicle screw based posterior dynamic stabilization (PDS) devices. Using Medline, Embase, and Scopus online databases, we identified four pedicle-screw-PDS devices for which both, biomechanical testing and clinical follow-up data are available: Graf artificial ligaments, Isobar TTL, Polyetheretherketone rods, and Dynesys. The current state-of-the-art of pedicle-screw-PDS devices is far from achieving its desired biomechanical efficacy, which has resulted in a weak support for the posited clinical benefits. Although pedicle-screw-PDS devices are useful in salvaging a moderately degenerate functionally suboptimal disc, for severe disc degeneration cases fusion is still the preferred choice. We conclude that a pedicle-screw-PDS device should aim at restoring load sharing amongst spinal elements while preserving the qualitative and quantitative nature of spinal motion, especially minimize posterior shift of the helical axis of motion. More precise and objective assessment techniques need to be standardized for in vivo evaluation of intervertebral motion and load sharing amongst spinal elements across different pedicle-screw-PDS devices.

Chamoli|Uphar|U|
Diwan|Ashish D|AD|
Tsafnat|Naomi|N|

dynamic stabilization
isobar TTL
Dynesys
Graf ligaments
PEEK rods
pedicle screw PDS devices
posterior spinal stabilization


Protective effect of electro-acupuncture on liver ischemia-reperfusion injury in rats.

Abstract: Liver ischemia-reperfusion injury is an important clinical complication in which excessive inflammation is a key factor; however, few studies have provided effective means of its regulation. As previous studies suggested that electro-acupuncture (EA) is able control excessive inflammation, the present study aimed to explore its effects on liver ischemia-reperfusion injury in experimental rats. The animals were randomly divided into surgery and sham groups, which were further divided into four sub-groups, including a non-treatment (NT), a non-point acupuncture (NPA), the non-selective nicotinic acetylcholine receptor (AChR) agonist 1,1-dimethyl-4-phenyl L-pioperazinium iodide (DMPPI) and an EA group. The alanine aminotransferase (ALT), serum cytokine and myeloperoxidase (MP) levels and the tissue pathology were evaluated after 90 min of ischemia followed by a 4, 8 or 24 h reperfusion. The results demonstrated that EA and DMPPI suppressed serum ALT elevation at 4 and 8 h reperfusion, whereas NPA did not. I/R induced hepatocellular necrosis, and cytoplasmic vacuolization and sinusoidal congestion was ameliorated by EA treatment after an 8 and 24 h reperfusion. In addition, EA also inhibited liver neutrophil accumulation, evidenced by a decreased MPO level at 8 h reperfusion. EA also suppressed the release of serum inflammatory factors TNF-α and IL-6 for the duration of reperfusion. However, little influence on IL-10 was observed. Mechanistically, vagus block by subphrenic vagotomy or mecamylamine hydrochloride abolished EA effect on liver damage, neutrophil accumulation and inflammatory factor release. In conclusion, it was demonstrated that EA protects the liver against I/R induced injury by inhibiting the inflammatory response, which is associated with the vagus.

Li|Yesheng|Y| Chen|Yi|Y| Zhang|Xinji|X| Geng|Li|L| Dai|Binghua|B| Lv|Xin|X| Zhang|Ping|P| Li|Honghai|H| Yang|Jiamei|J| Huang|Yangqing|Y| Xu|Feng|F|


Chlorpyrifos stimulates expression of vitamin D3 receptor in skin cells irradiated with UVB.

Abstract: Skin, the organ responsible for vitamin D synthesis, is fully exposed to many xenobiotics, e.g. polycyclic aromatic hydrocarbons and pesticides. A broad spectrum organophosphorus insecticides (OP's), such as chlorpyrifos (CPS), are commonly used in agriculture and to control domestic insects. Thus, the aim of this study was to investigate the effect of chlorpyrifos, on the expression of vitamin D3 receptor (VDR) in human keratinocytes cell line HaCaT and fibroblasts cell line BJ. The impact of CPS and UVB radiation on cell viability were examined by Neutral Red assay. The effect of CPS on VDR expression was evaluated by RT-qPCR and flow cytometry (FC). The presented study demonstrated that exposure to CPS and UVB significantly affects the viability of HaCaT and BJ cells lines. Results also revealed that exposure to CPS induced the expression at mRNA and protein level of VDR nuclear receptor in both cell lines exposed to UVB. In HaCaT incubated with 250 μM CPS and 15 mJ/cm2 UVB, the relative VDR expression was ∼2-fold higher; whereas in BJ incubated with 250 μM CPS and 20 mJ/cm2, UVB was∼3-fold higher. Results from FC confirmed this result, as VDR expression increased by ~250% in HaCaT incubated with 250 μM CPS and 20 mJ/cm2 UVB, and in BJ incubated with 250 μM CPS, and 20 mJ/cm2 UVB cells VDR expression increased by ~190%, compared with control. It can therefore be concluded that OPs pesticide might interfere with vitamin D3 metabolism in skin cells.

Sawicki|Krzysztof|K| Czajka|Magdalena|M| Matysiak-Kucharek|Magdalena|M| Kruszewski|Marcin|M| Skawiński|Waldemar|W| Brzóska|Kamil|K| Kapka-Skrzypczak|Lucyna|L|

Chlorpyrifos
Skin cells
VDR
Keratinocytes
Fibroblasts
Vitamin D(3)


Second-Look Endoscopy in Hospitalized Severe Ulcerative Colitis: A Retrospective Cohort Study.

Abstract:
BACKGROUND
Acute severe ulcerative colitis (ASUC) is a serious complication of ulcerative colitis (UC). Management of partial responders to steroids or rescue therapy remains challenging. Whether there is a role for re-look sigmoidoscopic evaluation in disease management is unknown.

METHODS
Our study cohort consisted of patients who underwent 2 sigmoidoscopic procedures during the same index hospitalization for ASUC at our center. Reasons for repeat endoscopic evaluation and endoscopic and histologic severity of inflammation during both procedures were noted. Multivariable regression models were performed to identify predictors of improvement at the second endoscopic assessment and to determine the independent effect of such an improvement on in-hospital colectomy and at 3, 6, and 12 months.

RESULTS
Our study included 49 patients (mean age, 42 years; 52% women). Just under one-third of patients (30%) were noted to have improved endoscopic appearance at the second sigmoidoscopy, at a median of 9 days after initial exam. None of the patients who had improvement on the second endoscopy underwent in-hospital colectomy, compared with 46% of those with worsening or persistent disease (P = 0.002). Similar differences in the improved group persisted at 3 months (P = 0.007) and 6 months (P = 0.027). Histologic severity at the first endoscopy was associated with increased risk of colectomy in-hospital (odds ratio, 3.8; 95% confidence interval, 1.02-14.21) and at 3 and 6 months.

CONCLUSIONS
After a median interval of 9 days, endoscopic improvement was noted in 30% of patients with ASUC undergoing a second sigmoidoscopy, which predicted lower rates of colectomy in-hospital and at 3 and 6 months.

Borren|Nienke Z|NZ|
Khalili|Hamed|H|
Luther|Jay|J|
Colizzo|Francis P|FP|
Garber|John J|JJ|
Ananthakrishnan|Ashwin N|AN|

endoscopy
hospitalization
ulcerative colitis
colectomy


Hemodialysis in children with ventriculoperitoneal shunts: prevalence, management and outcomes.

Abstract:
BACKGROUND
Hemodialysis (HD) in children with a concomitant ventriculoperitoneal shunt (VPS) is rare. Registry data suggest that peritoneal dialysis with a VPS is safe, but little is known about HD in the presence of a VPS.

METHODS
We performed a 10-year survey to determine the prevalence of a VPS, complications and outcome in children with a VPS on HD in 15 dialysis units from the 13 countries participating in the European Pediatric Dialysis Working Group.

RESULTS
Eleven cases of HD with a VPS were reported (prevalence 1.33 %; 328 patient-months) and compared with prospective Registry data. The median age at start of dialysis was 9.6 [inter-quartile range (IQR) 1.0-15.0] years and median HD vintage was 2.4 (IQR 1.7-3.0) years. Dialysis was performed through a central venous line (CVL) and through an arteriovenous fistula in six and five children, respectively. Three CVL infections occurred in two children, but these children did not develop VPS infections or meningitis. Symptoms of hemodynamic instability were reported in six (55 %) children at least once per week, with hypotension or hypertension occurring in four of these children and nausea, vomiting and headaches occurring in two; four other children reported less frequent symptoms. Seizures on dialysis occurred in two children, at a frequency of less than once per month, with one child also experiencing visual disturbances. During follow-up (median 4.0; IQR 0.38-7.63 years), three children remained on HD and eight had a functioning transplant. No patients were switched to PD.

CONCLUSIONS
Hemodialysis in children with a VPS is safe, but associated with frequent symptoms of hemodynamic instability. No episodes of VPS infection or meningitis were seen among the children in the survey, not even in those with CVL sepsis.

Wright|Elizabeth|E|
Fischbach|Michel|M|
Zaloszyc|Ariane|A|
Paglialonga|Fabio|F|
Aufricht|Christoph|C|
Dufek|Stephanie|S|
Bakkaloğlu|Sevcan|S|
Klaus|Günter|G|
Zurowska|Aleksandra|A|
Ekim|Mesiha|M|
Ariceta|Gema|G|
Holtta|Tuula|T|
Jankauskiene|Augustina|A|
Schmitt|Claus Peter|CP|
Stefanidis|Constantinos J|CJ|
Walle|Johan Vande|JV|
Vondrak|Karel|K|
Edefonti|Alberto|A|
Shroff|Rukshana|R|
|||

Hemodialysis
Children
Ventriculoperitoneal shunt
Central venous line
Seizures


Safety of nelarabine in adults with relapsed or refractory T-cell acute lymphoblastic leukemia/lymphoma.

Abstract:
INTRODUCTION
T-cell acute lymphoblastic leukemia (T-ALL) and lymphoma (T-LBL) are aggressive hematological malignancies accounting for 15-20% of adult acute lymphoproliferative diseases. Treatment of relapsed/refractory (R/R) T-ALL/T-LBL is challenging with very few therapeutic options.

AREAS COVERED
This report provides a concise review on the efficacy and safety of nelarabine monotherapy in adults with R/R T-ALL and T-LBL.

EXPERT OPINION
Nelarabine is approved for the treatment of adults with R/R T-ALL/T-LBL in the setting of third or more line of therapy. Hematological and neurological toxicities are the most frequent adverse events. Grade 3 and 4 neutropenia and thrombocytopenia are common, however with treatment-related deaths accounting only for 1-2% of patients. Neurological toxicity is typically characterized by a reversible peripheral neuropathy, usually mild or moderate and without treatment delay. Other neurological (somnolence and depressed level of consciousness) or extra-neurological adverse events are uncommon and rarely severe. In conclusion, nelarabine is a well tolerated and effective salvage therapy in patients with R/R T-ALL/T-LBL and has acquired an important role as a bridge-therapy to allogeneic stem cell transplantation.

D018380:Hematopoietic Stem Cell Transplantation

D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

Nelarabine
acute lymphoblastic leukemia
lymphoblastic lymphoma
neurotoxicity


Cross-border emergence of clonal lineages of ST38 Escherichia coli producing the OXA-48-like carbapenemase OXA-244 in Germany and Switzerland.

Abstract:
BACKGROUND
Carbapenemase-producing Gram-negative bacteria cause infections that are difficult to treat and represent a rising threat to healthcare systems worldwide. This study analysed isolates of Escherichia coli (E. coli), a species associated with nosocomial-acquired and community-acquired infections, from hospitals in Germany and Switzerland exhibiting a slight decrease in susceptibility to carbapenems.

METHODS
E. coli strains from Germany and Switzerland, obtained mainly in 2019, were first screened for carbapenemase genes by PCR and subsequently whole-genome-sequenced and analysed for their clonal relationship using multilocus sequence typing, single nucleotide polymorphisms, virulence and antibiotic-resistance gene content.

RESULTS
The analysis revealed the presence of extended β-lactamase (ESBL)-producing E. coli clones producing OXA-244, a point-mutation derivative of OXA-48, with a predominance of isolates exhibiting the sequence type (ST) ST38 in both Germany and Switzerland. These clustered exclusively into two distinct lineages: one encoding CTX-M-27, a recently emerged extended-spectrum β-lactamase, and the other CTX-M-14b. All OXA244/CTX-M-27 ST38 isolates harboured the Dr adhesin operon and a representative isolate exhibited a diffuse adherence (DAEC) phenotype and was invasive for Hela cells.

CONCLUSION
Clonal lineages of ST38 are members of E. coli phylogenetic group D commonly associated with extra-intestinal infections. Their increased isolation in two different European countries indicates ongoing spread of ST38 ESBL-producing and OXA-244-producing E. coli clonal lineages. It is possible that members of the multidrug-resistant DEAC ExPEC group have expanded globally, but that this is currently underreported because of the inherent difficulty in detecting isolates expressing the OXA-244 allele.

Falgenhauer|Linda|L|
Nordmann|Patrice|P|
Imirzalioglu|Can|C|
Yao|Yancheng|Y|
Falgenhauer|Jane|J|
Hauri|Anja M|AM|
Heinmüller|Petra|P|
Chakraborty|Trinad|T|

D024901:Drug Resistance, Multiple, Bacterial


Up-regulation of cyclinD1 and Bcl2A1 by insulin is involved in osteoclast proliferation.

Abstract:
AIMS
Insulin receptor signaling in osteoblasts has been well established, but the effects of insulin on osteoclast proliferation are poorly explored. The objective of this study was to investigate the roles and the mechanisms of insulin on osteoclast proliferation.

MAIN METHODS
After insulin treatment to primary osteoclast precursors, BrdU incorporation assay was performed and the expression of cell cycle- and apoptosis-related genes was determined by real-time PCR and immunoblotting. Apoptosis was analyzed using a FACScan flow cytometer.

KEY FINDINGS
Insulin activated insulin receptor and promoted the proliferation of osteoclast precursors in time- and dose-dependent manners. However, the expression of insulin receptor was not changed by it during that time. Insulin remarkably induced the expression of cyclinD1, a cell cycle marker, and Bcl2A1, an anti-apoptotic oncogene, whereas cdk1 and cdk4 were not affected by it. The expression of Bcl2l11 and Bax, both apoptotic markers, was reduced or not changed in osteoclast precursors. Bcl2A1/Bax ratio was also increased in protein levels. Treatment with obatoclax, a Bcl2 family inhibitor, significantly induced the apoptosis of osteoclast precursors in the presence of insulin. These results demonstrate that insulin promotes osteoclast proliferation by increasing cell cycle and suppressing apoptosis through specific gene regulation.

SIGNIFICANCE
These data provide a basis for understanding and ultimately treating several bone-related metabolic diseases.

D060888:Real-Time Polymerase Chain Reaction


Lab experience with seafood control at the undergraduate level: Cephalopods as a case study.

Abstract: The correct labeling of seafood is important to protect nature and the rights of consumers. Given the certainty that the resources of the sea are not inexhaustible, only strict regulations and the implementation of sustainable fishing systems and reliable and traceable marketing systems can help ensure the long-term sustainability of fishery resources. Detecting mislabeling and seafood fraud is a useful resource for improving students' motivation and developing active learning methodologies in higher education. In the present study, we have proposed to the students a lab exercise consisting of exploring 25 different commercial cephalopod products from three major European supermarkets by using DNA barcoding and analyzing the results under the framework of EU and Spanish regulations. The problem is connected with the last theme (traceability) of the Conservation Genetics and Breeding course with the aim of providing students with a practical research lab experience about a real problem before going deeper into more theoretical contents. In this way, they can use the knowledge and the skills they acquired previously to better comprehend and think critically about the problem. Findings from students' answers to a survey revealed that the use of this approach generates useful information for communities, increases curiosity and feelings of benefit, and leads to high levels of satisfaction with lab practices compared with those in other courses. In conclusion, lab exercises focused on seafood control, in addition to being viable, can be used as a tool in classes to improve students' commitment to higher education.

Fernández|Sara|S|0000-0002-6290-588X
Rodríguez-Muñiz|Luis J|LJ|
Molina|Jara|J|
Muñiz-Rodríguez|Laura|L|
Jiménez|Juan|J|
García-Vázquez|Eva|E|
Borrell|Yaisel J|YJ|0000-0003-2840-4384

D003247:Conservation of Natural Resources

lab experiences
seafood control
cephalopods
barcoding
university


Evaluation of a two rubber band technique for finger ring removal.

Abstract:
INTRODUCTION
Rings are required to be removed from a finger in many clinical situations. Rings that are difficult to remove is a problem encountered frequently. Many techniques have been reported for this problem. This study looks at the effectiveness of a single technique for removing difficult rings from fingers.

METHODS
A two rubber band technique was used in this study of 69 difficult to remove rings. Success of the technique and time to removal were recorded.

RESULTS
Difficult rings were removed in 92.5% of cases, in a mean time of 10.7 seconds. No fingers or rings suffered damage during the study.

CONCLUSIONS
This two rubber band technique is a rapid, safe and effective method for removing rings that cannot be removed easily.

Kingston|D|D| Bopf|D|D| Dhanjee|U|U| McLean|A|A|


Suicidal behaviour of Indian patients with obsessive compulsive disorder.

Abstract:
BACKGROUND SETTING AND DESIGN
The chronicity, distress, high rates of comorbidity and varying degree of non response to treatment in Obsessive Compulsive Disorder (OCD) may contribute to suicidal behavior. There is relatively little information on suicidal behavior in OCD subjects. Our study design is Single point non-invasive, cross sectional, clinical study of new and follow up cases.

MATERIALS AND METHODS
Assessment of Suicidal Behavior in patients of OCD attending the adult Psychiatry O.P.D. of Chatrapati Shahuji Maharaj Medical University (CSMMU) U.P. Lucknow using (DSM-IV) criteria for diagnosis of Obsessive Compulsive Disorder, Structured Clinical Interview for DSM-IV Axis-I disorders, Yale Brown Obsessive Compulsive Rating Scale, Scale for Suicidal Ideation (SSI), Beck's Hopelessness Scale (BHS).

STATISTICAL ANALYSIS
Mean standard deviation and t test for independent samples, Pearson's correlation coefficient.

RESULTS
Statistically significant differences were seen in the SSI score between the "Clinical" and "Sub-Clinical" cases with Clinical group having higher scores. Value of correlation coefficient between YBOCS score and SSI and BHS score is positive and statistically significant (P<0.01).

CONCLUSION
"Clinical" group of patients had significantly higher scores of suicidal ideation measured by Scale of Suicidal Ideation (SSI). There was a significantly positive correlation between disease severity (YBOCS Score) and degree of suicidal ideation (SIS Score).

Dhyani|Mohan|M|
Trivedi|Jitendra Kumar|JK|
Nischal|Anil|A|
Sinha|Pramod Kumar|PK|
Verma|Subham|S|

suicide
obsessive compulsive disorder
India


Sodium channel SCN8A (Nav1.6): properties and de novo mutations in epileptic encephalopathy and intellectual disability.

Abstract: The sodium channel Nav1.6, encoded by the gene SCN8A, is one of the major voltage-gated channels in human brain. The sequences of sodium channels have been highly conserved during evolution, and minor changes in biophysical properties can have a major impact in vivo. Insight into the role of Nav1.6 has come from analysis of spontaneous and induced mutations of mouse Scn8a during the past 18 years. Only within the past year has the role of SCN8A in human disease become apparent from whole exome and genome sequences of patients with sporadic disease. Unique features of Nav1.6 include its contribution to persistent current, resurgent current, repetitive neuronal firing, and subcellular localization at the axon initial segment (AIS) and nodes of Ranvier. Loss of Nav1.6 activity results in reduced neuronal excitability, while gain-of-function mutations can increase neuronal excitability. Mouse Scn8a (med) mutants exhibit movement disorders including ataxia, tremor and dystonia. Thus far, more than ten human de novo mutations have been identified in patients with two types of disorders, epileptic encephalopathy and intellectual disability. We review these human mutations as well as the unique features of Nav1.6 that contribute to its role in determining neuronal excitability in vivo. A supplemental figure illustrating the positions of amino acid residues within the four domains and 24 transmembrane segments of Nav1.6 is provided to facilitate the location of novel mutations within the channel protein.

O'Brien|Janelle E|JE|
Meisler|Miriam H|MH|

SCN8A
Nav1.6
intellectual disability
exomes
epilepsy
genetics
neurogenetics
voltage-gated sodium channels


BRCA Gene Mutations and Poly(ADP-Ribose) Polymerase Inhibitors in Triple-Negative Breast Cancer.

Abstract: Breast cancer is the most common cancer in women worldwide. Treatment is chosen according to its hormone receptor status and human epidermal growth factor receptor 2 (HER2) status. Among the four main clinically set subtypes, hormone receptor-negative/HER2-negative subtype, also called triple-negative subtype (TNBC), is the most aggressive type with limited choices of therapy. However, recent research has provided important new insights into effective treatments for this subtype. One molecular target that has gained attention is the BRCA gene. BRCA proteins are involved in the maintenance of genomic integrity, therefore playing an important role as a "caretaker" DNA repair protein. Approximately 5% of all breast cancer patients are BRCA mutation carriers, and among the patients with BRCA mutations, 57.1% have the clinical TNBC subtype, showing a high association between BRCA mutations and TNBCs. When cells lack either BRCA1 or BRCA2, all types of homology-directed repairs are compromised, and poly(ADP-ribose) (PAR) polymerase (PARP) acts as a backup system to maintain the genome, consequently making the cells highly sensitive to PARP1 inhibitors. PARP inhibitors have shown promising activity in preclinical and early clinical trials, and today, phase III trials are ongoing. In this chapter, we discuss the mechanism and the role of PARP inhibitors in BRCA-mutated breast cancers and further elaborate the clinical potential of PARP inhibitors as well as their barriers.

D064726:Triple Negative Breast Neoplasms

Triple-negative breast cancer
BRCA mutation
PARP inhibitor
Synthetic lethality


High-throughput and automation advances for accelerating single-cell cloning, monoclonality and early phase clone screening steps in mammalian cell line development for biologics production.

Abstract: Mammalian cell line development is a multistep process wherein timelines for developing clonal cells to be used as manufacturing cell lines for biologics production can commonly extend to 9 months when no automation or modern molecular technologies are involved in the workflow. Steps in the cell line development workflow involving single-cell cloning, monoclonality assurance, productivity and stability screening are labor, time and resource intensive when performed manually. Introduction of automation and miniaturization in these steps has reduced the required manual labor, shortened timelines from months to weeks, and decreased the resources needed to develop manufacturing cell lines. This review summarizes the advances, benefits, comparisons and shortcomings of different automation platforms available in the market for rapid isolation of desired clonal cell lines for biologics production.

automation
single-cell cloning
cell line development
monoclonality assurance
productivity screening


The evolving concept of SLE comorbidities.

Abstract: The survival of SLE patients has improved significantly over the past few decades placing them at increased risk of cardiovascular disease (CVD), malignancies, and osteoporosis, among other comorbidities. The aim of this review was to assess the incidence and prevalence of comorbidities in these patients as well as their prevention and treatment focusing in CVD, malignancies and osteoporosis. Areas covered: We focused on CVD, malignancies and osteoporosis as SLE comorbidities. A literature search (PubMed database) was performed using the words 'comorbidities', 'cardiovascular disease', 'osteoporosis', 'malignancy', 'cancer' and 'lupus' between January 1976 and December 2016. No language restrictions were placed. More than 100 full-length articles were reviewed. Expert commentary: The therapeutic approach in SLE should aim not only at achieving disease remission but also at treating all conditions affecting the patients and, consequently, their outcomes. These patients should be treated as coronary artery disease (CAD) equivalent with rigorous modifiable CV risk factors management in addition to the optimal treatment of their lupus. Furthermore, modifiable osteoporosis traditional risk factors and SLE-related risk factors should be modified to ameliorate bone loss and fracture risk. Cancer preventive measures (smoking cessation and screening programs for cervical cancer) constitute also essential components of the management of these patients.

Comorbidity
cardiovascular disease
malignancy
osteoporosis
systemic lupus erythematosus


Effects of Replacement of Soybean Meal by Fermented Cottonseed Meal on Growth Performance, Serum Biochemical Parameters and Immune Function of Yellow-feathered Broilers.

Abstract: The study was conducted to examine the effects of partially replacing soybean meal (SBM) by solid-state fermented cottonseed meal (FCSM) on growth performance, serum biochemical parameters and immune function of broilers. After inoculated with Bacillus subtilis BJ-1 for 48 h, the content of free gossypol in cottonseed meal was decreased from 0.82 to 0.21 g/kg. A total of 600, day-old male yellow-feathered broilers were randomly divided into four groups with three replicates of 50 chicks each. A corn-SBM based control diet was formulated and the experimental diets included 4, 8 or 12% FCSM, replacing SBM. Throughout the experiment, broilers fed 8% FCSM had higher (p<0.05) body weight gain than those fed 0, 4 and 12% FCSM. The feed intake in 8% FCSM group was superior (p<0.05) to other treatments from d 21 to 42. On d 21, the concentration of serum immunoglobin M in the 4% and 8% FCSM groups, as well as the content of complements (C3, C4) in 8% FCSM group were greater (p<0.05) than those in the SBM group. Besides, birds fed 8% FCSM had increased (p<0.05) serum immunoglobin M, immunoglobulin G and complement C4 levels on d 42 compared with bird fed control diet. No differences (p>0.05) were found between treatments regarding the serum biochemical parameters and the relative weights of immune organs. In conclusion, FCSM can be used in broiler diets at up to 12% of the total diet and an appropriate replacement of SBM with FCSM may improve growth performance and immunity in broilers.

Tang|J W|JW|
Sun|H|H|
Yao|X H|XH|
Wu|Y F|YF|
Wang|X|X|
Feng|J|J|

Fermented Cottonseed Meal
Growth Performance
Immune Function
Yellow-feathered Broiler
Bacillus subtilis
Serum Parameters


Perivascular spaces, glymphatic dysfunction, and small vessel disease.

Abstract: Cerebral small vessel diseases (SVDs) range broadly in etiology but share remarkably overlapping pathology. Features of SVD including enlarged perivascular spaces (EPVS) and formation of abluminal protein deposits cannot be completely explained by the putative pathophysiology. The recently discovered glymphatic system provides a new perspective to potentially address these gaps. This work provides a comprehensive review of the known factors that regulate glymphatic function and the disease mechanisms underlying glymphatic impairment emphasizing the role that aquaporin-4 (AQP4)-lined perivascular spaces (PVSs), cerebrovascular pulsatility, and metabolite clearance play in normal CNS physiology. This review also discusses the implications that glymphatic impairment may have on SVD inception and progression with the aim of exploring novel therapeutic targets and highlighting the key questions that remain to be answered.

Mestre|Humberto|H|
Kostrikov|Serhii|S|
Mehta|Rupal I|RI|
Nedergaard|Maiken|M|

Perivascular space
Glymphatic
Small vessel disease
CNS clearance
Cerebrospinal fluid


A Delamination Strategy for Thinly Layered Defect-Free High-Mobility Black Phosphorus Flakes.

Abstract: Extraordinary electronic and photonic features render black phosphorus (BP) an important material for the development of novel electronics and optoelectronics. Despite recent progress in the preparation of thinly layered BP flakes, scalable synthesis of large-size, pristine BP flakes remains a major challenge. An electrochemical delamination strategy is demonstrated that involves intercalation of diverse cations in non-aqueous electrolytes, thereby peeling off bulk BP crystals into defect-free flakes comprising only a few layers. The interplay between tetra-n-butylammonium cations and bisulfate anions promotes a high exfoliation yield up to 78 % and large BP flakes up to 20.6 μm. Bottom-gate and bottom-contact field-effect transistors, comprising single BP flakes only a few layers thick, exhibit a high hole mobility of 252±18 cm2  V-1  s-1 and a remarkable on/off ratio of (1.2±0.15)×105 at 143 K under vacuum. This efficient and scalable delamination method holds great promise for development of BP-based composites and optoelectronic devices.

Yang|Sheng|S|0000-0002-3306-9229
Zhang|Ke|K|
Ricciardulli|Antonio Gaetano|AG|
Zhang|Panpan|P|
Liao|Zhongquan|Z|
Lohe|Martin R|MR|
Zschech|Ehrenfried|E|
Blom|Paul W M|PWM|
Pisula|Wojciech|W|
Müllen|Klaus|K|
Feng|Xinliang|X|0000-0003-3885-2703

black phosphorus
exfoliation
field-effect transistors
electrochemistry
two-dimensional flakes


Atypical magnetic resonance imaging features and differential diagnosis of hepatocellular carcinoma.

Abstract:
OBJECTIVE
Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver. We aimed to summarize and analyze the atypical magnetic resonance imaging (MRI) features of HCC to improve its diagnostic accuracy.

METHODS
We retrospectively analyzed MRI data for 66 patients with HCC with atypical MRI features confirmed by operation and pathology.

RESULTS
Twelve patients had high signals and 18 patients had significant decreases in opposed phase signals in T1WI plain scans. Nine patients had high signals and six patients had large cystic lesions in apparent diffusion coefficient images. Dynamic enhancement showed progressive enhancement in 15 patients, ring enhancement in three, irregular patchy enhancement in three, 'nodule-in-nodule' enhancement in six, delayed central patchy enhancement in six, delayed central 'star-like aristate scars' (T2WI revealed high signal intensity) in 21, and poor blood supply in three patients.

CONCLUSIONS
MRI can make a clear diagnosis of typical HCC, and atypical cases can also be distinguished from other tumors or tumor-like lesions by MRI. The analysis of atypical signs may improve the diagnostic accuracy of MRI for HCC.

D006528:Carcinoma, Hepatocellular
D003287:Contrast Media
D003937:Diagnosis, Differential
D006801:Humans
D008113:Liver Neoplasms
D008279:Magnetic Resonance Imaging
D012189:Retrospective Studies

atypical
magnetic resonance imaging
differential diagnosis
Hepatocellular carcinoma
enhancement
pathological section


Incidence of pedicle breach following open and minimally invasive spinal instrumentation: A postoperative CT analysis of 513 pedicle screws applied under fluoroscopic guidance.

Abstract:
Background
Even though pedicle screw application is a common procedure, and in-spite of spine surgeons being proficient with the technique, mal-positioning of pedicle screws can still occur. We intend to determine by postoperative CT analysis, the incidence of pedicle screw breach in the thoracolumbar spine despite satisfactory intraoperative placement confirmed by fluoroscopy.

Materials and methods
Consecutive patients diagnosed with thoracolumbar fractures who underwent open or minimally invasive posterior stabilization under fluoroscopic guidance were retrospectively reviewed. Postoperative CT scans of patients were analysed to determine the incidence of pedicle breach despite satisfactory intraoperative placement, and also to determine the factors that can predict a breach during intraoperative assessment.

Results
A total of 61 patients with 513 thoracolumbar pedicle screws were available for analysis. Based on our postoperative CT assessment, 28 screws (5.5%; 18 thoracic screws; 10 lumbar screws) had breached the pedicle. There were 14 minor (<3 mm) and 14 major (≥3 mm) breaches. The minimally invasive technique had a significantly lower breach rate compared to open surgery (1.9% vs. 7.9%). By retrospectively analysing the intra-operative fluoroscopic images, we determined certain parameters that could predict a breach during surgery.

Conclusion
Pedicle breaches can still be present despite satisfactory placement of screws visualized intra-operatively. A medial breach is most likely when the length of the pedicle screw spans only up to 50% of the vertebral body as seen on the lateral view but the pedicle screw tip has already transgressed the midline as seen on an AP view. A lateral breach is likely when the tip of the pedicle screw is overlapped by the screw head or is only minimally visualized on an AP view.

Chong|Xue Ling|XL|
Kumar|Aravind|A|
Yang|Eugene Wei Ren|EWR|
Kaliya-Perumal|Arun-Kumar|AK|
Oh|Jacob Yoong-Leong|JY|

Pedicle Screws
Spine
Fluoroscopy
Spinal Fractures
Vertebral column


MP-12 virus containing the clone 13 deletion in the NSs gene prevents lethal disease when administered after Rift Valley fever virus infection in hamsters.

Abstract: Rift Valley fever virus (RVFV; Bunyaviridae, Phlebovirus) causes a range of illnesses that include retinitis, fulminant hepatitis, neurologic disease, and hemorrhagic fever. In hospitalized individuals, case fatality rates can be as high as 10-20%. There are no vaccines or antivirals approved for human use to prevent or treat severe RVFV infections. We previously tested the efficacy of the MP-12 vaccine strain and related variants with NSs truncations as a post-exposure prophylaxis in mice infected with wild-type pathogenic RVFV strain ZH501. Post-exposure efficacy of the rMP12-C13type, a recombinant MP-12 vaccine virus which encodes an in-frame truncation removing 69% of the NSs protein, resulted in 30% survival when administering the virus within 30 min of subcutaneous ZH501 challenge in mice, while the parental MP-12 virus conferred no protection by post-exposure vaccination. Here, we demonstrate uniform protection of hamsters by post-exposure vaccination with rMP12-C13type administered 6 h post-ZH501 infection while no efficacy was observed with the parental MP-12 virus. Notably, both the MP-12 and rMP12-C13type viruses were highly effective (100% protection) when administered 21 days prior to challenge. In a subsequent study delaying vaccination until 8, 12, and 24 h post-RVFV exposure, we observed 80, 70, and 30% survival, respectively. Our findings indicate that the rapid protective innate immune response elicited by rMP12-C13type may be due to the truncated NSs protein, suggesting that the resulting functional inactivation of NSs plays an important role in the observed post-exposure efficacy. Taken together, the data demonstrate that post-exposure vaccination with rMP12-C13type is effective in limiting ZH501 replication and associated disease in standard pre-exposure vaccination and post-challenge treatment models of RVFV infection, and suggest an extended post-exposure prophylaxis window beyond that initially observed in mice.

Gowen|Brian B|BB|
Westover|Jonna B|JB|
Sefing|Eric J|EJ|
Bailey|Kevin W|KW|
Nishiyama|Shoko|S|
Wandersee|Luci|L|
Scharton|Dionna|D|
Jung|Kie-Hoon|KH|
Ikegami|Tetsuro|T|

Rift Valley fever virus
phlebovirus
vaccine
post-exposure
viral hemorrhagic fever


A Novel Birthdate-Labeling Method Reveals Segregated Parallel Projections of Mitral and External Tufted Cells in the Main Olfactory System.

Abstract: A fundamental strategy in sensory coding is parallel processing, whereby unique, distinct features of sensation are computed and projected to the central target in the form of submodal maps. It remains unclear, however, whether such parallel processing strategy is employed in the main olfactory system, which codes the complex hierarchical odor and behavioral scenes. A potential scheme is that distinct subsets of projection neurons in the olfactory bulb (OB) form parallel projections to the targets. Taking advantage of the observation that the distinct projection neurons develop at different times, we developed a Cre-loxP-based method that allows for birthdate-specific labeling of cell bodies and their axon projections in mice. This birthdate tag analysis revealed that the mitral cells (MCs) born in an early developmental stage and the external tufted cells (TCs) born a few days later form segregated parallel projections. Specifically, the latter subset converges the axons onto only two small specific targets, one of which, located at the anterolateral edge of the olfactory tubercle (OT), excludes widespread MC projections. This target is made up of neurons that express dopamine D1 but not D2 receptor and corresponds to the most anterolateral isolation of the CAP compartments (aiCAP) that were defined previously. This finding of segregated projections suggests that olfactory sensing does indeed involve parallel processing of functionally distinct submodalities. Importantly, the birthdate tag method used here may pave the way for deciphering the functional meaning of these individual projection pathways in the future.

Hirata|Tatsumi|T|0000-0001-5218-2959 Shioi|Go|G| Abe|Takaya|T| Kiyonari|Hiroshi|H| Kato|Shigeki|S| Kobayashi|Kazuto|K| Mori|Kensaku|K|0000-0001-7853-9370 Kawasaki|Takahiko|T|

tufted cell
olfactory system
birthdate tag
olfactory tubercle
dopamine
parallel pathway


The Pain of Sleep Loss: A Brain Characterization in Humans.

Abstract: Sleep loss increases the experience of pain. However, the brain mechanisms underlying altered pain processing following sleep deprivation are unknown. Moreover, it remains unclear whether ecologically modest night-to-night changes in sleep, within an individual, confer consequential day-to-day changes in experienced pain. Here, we demonstrate that acute sleep deprivation amplifies pain reactivity within human (male and female) primary somatosensory cortex yet blunts pain reactivity in higher-order valuation and decision-making regions of the striatum and insula cortex. Consistent with this altered neural signature, we further show that sleep deprivation expands the temperature range for classifying a stimulus as painful, specifically through a lowering of pain thresholds. Moreover, the degree of amplified reactivity within somatosensory cortex following sleep deprivation significantly predicts this expansion of experienced pain across individuals. Finally, outside of the laboratory setting, we similarly show that even modest nightly changes in sleep quality (increases and decreases) within an individual determine consequential day-to-day changes in experienced pain (decreases and increases, respectively). Together, these data provide a novel framework underlying the impact of sleep loss on pain and, furthermore, establish that the association between sleep and pain is expressed in a night-to-day, bidirectional relationship within a sample of the general population. More broadly, our findings highlight sleep as a novel therapeutic target for pain management within and outside the clinic, including circumstances where sleep is frequently short yet pain is abundant (e.g., the hospital setting).SIGNIFICANCE STATEMENT Are you experiencing pain? Did you have a bad night of sleep? This study provides underlying brain and behavioral mechanisms explaining this common co-occurrence. We show that sleep deprivation enhances pain responsivity within the primary sensing regions of the brain's cortex yet blunts activity in other regions that modulate pain processing, the striatum and insula. We further establish that even subtle night-to-night changes in sleep in a sample of the general population predict consequential day-to-day changes in pain (bidirectionally). Considering the societal rise in chronic pain conditions in lock-step with the decline in sleep time through the industrial world, our data support the hypothesis that these two trends may not simply be co-occurring but are significantly interrelated.

Krause|Adam J|AJ|0000-0001-5529-1296
Prather|Aric A|AA|0000-0003-1302-8283
Wager|Tor D|TD|0000-0002-1936-5574
Lindquist|Martin A|MA|
Walker|Matthew P|MP|


Recommendations for Addressing Structural Racism in Implementation Science: A Call to the Field.

Abstract: Implementation science (IS) has emerged in response to a striking research-to-practice gap, with the goal of accelerating and addressing the development, translation, and widespread uptake of evidence-based interventions (EBIs). Despite the promise of IS, critical gaps and opportunities remain within the field to explicitly facilitate health equity, particularly as they relate to the role of social determinants of health and structural racism. In this commentary, we propose recommendations for the field of IS to include structural racism as a more explicit focus of our work. First, we make the case for including structural racism as a construct and promote its measurement as a determinant within existing IS frameworks/models, laying the foundation for an empirical evidence base on mechanisms through which such factors influence inequitable adoption, implementation, and sustainability of EBIs. Second, we suggest considerations for both EBIs and implementation strategies that directly or indirectly address structural racism and impact health equity. Finally, we call for use of methods and approaches within IS that may be more appropriate for addressing structural racism at multiple ecological levels and clinical and community settings in which we conduct IS, including community-based participatory research and stakeholder engagement. We see these as opportunities to advance the focus on health equity within IS and conclude with a charge to the field to consider making structural racism and the dismantling of racism an explicit part of the IS research agenda.

Shelton|Rachel C|RC|
Adsul|Prajakta|P|
Oh|April|A|

Structural Racism
Racism
Implementation Science
Health Equity
Health Disparities


Predictors of Resilience and Posttraumatic Growth Among People Living with HIV: A Longitudinal Study.

Abstract: This longitudinal study investigated the predictors of HIV-related resilience (HR) and posttraumatic growth (PTG) among Spanish-speaking HIV-positive people. Perceived past resilience, internalised stigma, and coping strategies were hypothesised as possible predictors. Data were collected at two time points from 119 HIV-positive people. Path analyses with latent variables revealed that half of HR 8 months after diagnosis was predicted by rumination, emotional expression, positive thinking, internalised stigma, and perceived past resilience. The latter three, along with isolation, self-blame, thinking avoidance, and help seeking predicted some PTG dimensions 8 months after diagnosis. The results highlight the importance of internalised stigma associated with HIV infection and of the differential use of coping strategies, and point to the need for clinicians and policy makers to implement stigma reduction and appropriate coping strategies interventions.

Resilience
Posttraumatic growth
Coping
HIV-related stigma
HIV/AIDS


Craving and Drug Reward: A Comparison of Celecoxib and Ibuprofen in Detoxifying Opiate Addicts.

Abstract: Objective: Craving for substance abuse is a usual and complicated problem in patients, with opioid addiction who are in opioid detoxifying process. Craving has been added as one of the diagnostic criteria of substance use disorders in DSM-5. The present trial aimed at comparing the effects of celecoxib versus ibuprofen in reducing pain and decreasing the desire to use opiates in patients undergoing opiate detoxification (n = 32). Method: A total of 32 patients (both inpatients and outpatients), who were undergoing opiate detoxification procedure and met the inclusion criteria entered this 4- week study. Participants who suffered from pain due to opiate withdrawal were randomized into 2 groups: Group 1 received celecoxib 200 milligrams once per day and group 2 received ibuprofen 400 milligrams 4 times per day. Self-reported Desire for Drug Questionnaire (DDQ) and 0-10 numeric pain scale were used at baseline and at the end of the study to evaluate changes in opiate craving and pain, respectively. Data analysis was done by SPSS-21 statistical software. Results: In this study, 16 patients received celecoxib 200 milligrams once daily, and 16 received ibuprofen 400 milligrams 4 times daily. After 4 weeks of treatment with both ibuprofen and celecoxib, the results revealed that celecoxib and ibuprofen equally reduced the pain symptoms. After 4 weeks of treatment, with either ibuprofen or celecoxib, significant improvement was observed in decreasing the craving in the celecoxib group, but not in the ibuprofen group. Conclusion: The study revealed a significant difference between the celecoxib and ibuprofen group in reducing craving in patients with opiate craving after 4 weeks of treatment. However there were no significant differences between these two groups in reducing pain.

Jafari|Sara|S|
Khajehpour|Sana|S|
Razzaghi|Emran Mohammad|EM|
Heidari|Kazem|K|
Soleimani|Mehdi|M|
Ghaeli|Padideh|P|

Celecoxib
Ibuprofen
Pain
Desire for Drug Questionnaire
Opiate Craving


Salmonella Typhimurium DT 104 response to Lytic bacteriophage and Lactobionic acid on raw chicken breast.

Abstract: Bacterial food poisoning cases due to Salmonella have been linked with a variety of poultry products. This study evaluated the effects of a Salmonella-specific Lytic bacteriophage and Lactobionic acid (LBA) on Salmonella Typhimurium DT 104 growth on raw chicken breast meat. Each chicken breast was randomly assigned to a treatment group (Control, DI water, phage 1%, phage 5%, LBA 10 mg/mL, LBA 20 mg/mL, and phage 5% + LBA 20 mg/mL) with four chicken breasts per group. Samples were inoculated with 106 CFU/mL of Salmonella and stored at 4 °C for 30 min. The inoculated chicken breasts were randomly assigned to different storage time (0 h, 1 h, 24 h, or 48 h). Both time and treatment showed significance reduction (P < 0.0001) of microbial growth. The weight loss was significantly different (P < 0.0001) between treatments. The LBA treatments were not effective when compared to the control group, but Lytic bacteriophage significantly reduced the amount of microbial growth.

Walker|Nicole|N| Li|Sherita|S| Strauss|Hannah|H| Pokharel|Siroj|S|

Salmonella Typhimurium
Bacteriophage
Lactobionic acid
Raw chicken breast
Food safety


Effect of L-carnitine and atorvastatin on a rat model of ischemia-reperfusion injury of spinal cord.

Abstract: Pro-inflammatory cytokines and reactive oxygen species (ROS) are produced in acute spinal cord injury, leading to myelin breakdown, inflammation, mitochondrial dysfunction, and apoptosis of neurons and glial cells. The aim of the present study was to investigate possible protective effects of L-carnitine (carn) or atorvastatin (ator) on spinal cord ischemia-reperfusion injury (IRI). Rats were randomized into nine equal groups (n = 8): control and control taking carn (100 mg/kg BW), ator (2.5 mg/kg BW) or both, as well as sham-operation, IRI and IRI taking same doses of carn, ator or both. Neurological assessments were done 48 hours after IRI, and serum nitrite/nitrate was measured. Finally, lumbar segments of spinal cord were excised, and part was homogenized and prepared for measuring tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), malondialdehyde (MDA), advanced oxidation protein products (AOPP), reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase. The other part was sectioned for evaluation of histopathological changes and for immunostaining by glial fibrillary acidic protein (GFAP), Bax and Bcl-2. The IRI increased ROS (nitrite/nitrate, MDA, AOPP) and pro-inflammatory cytokines (TNF-α, IL-1β), and decreased antioxidants (GSH, GPx, SOD, catalase) with impaired sensory and motor functions. Astrogliosis was detected by GFAP, and increased apoptosis was demonstrated by increasing Bax and decreasing Bcl-2. Treatment with carn or ator alone decreased TNF-α, IL-1β, nitrite/nitrate, MDA and AOPP, and increased GSH, GPx, SOD, and catalase with improvement of neurological functions and histological studies. Combination of carn and ator improved most of measured IRI-affected parameters better than isolated carn or ator administration.

Hazzaa|Suzan M|SM|
Abdou|Asmaa Gaber|AG|
Ibraheim|Essam O|EO|
Salem|Esraa A|EA|
Hassan|Mohamad H A|MHA|
Abdel-Razek|Hesham A D|HAD|

l-carnitine
atorvastatin
ischemia-reperfusion injury
Spinal cord
immunohistochemistry


Intraparotid node metastases in adults with parotid mucoepidermoid cancer: an indicator of prognosis?

Abstract: We have retrospectively analysed the predictive value of intraparotid nodal metastases in patients having neck dissection for parotid mucoepidermoid cancer. The main outcomes were intraparotid nodal metastases, a new system for staging metastatic parotid nodes, and recurrence-free survival. The overall rate of intraparotid metastasis was 30/122 (25%), and seven patients had deep parotid nodal metastases. This metastasis was significantly related to tumour stage, neck disease, perineural invasion, lymphovascular invasion, and pathological tumour grade. The sensitivity of intraparotid nodal metastases in predicting neck disease was 50%, and the specificity of them predicting neck disease was 89%. The stages of the intraparotid nodes were as follows: P0 (n=92 patients), P1 (n=10), P2 (n=16), and P3 (n=4). A Cox's model analysis confirmed that the stage of the intraparotid nodes was an independent prognostic factor for recurrence, so the presence of intraparotid nodal metastases is associated with a higher risk for recurrence of disease.

intraparotid node
mucoepidermoid cancer
intraparotid node metastasis
parotid cancer
salivary gland tumour


Stem cell factor induces polarization of microglia to the neuroprotective phenotype in vitro.

Abstract: Microglia are classified mainly into the M1 or M2 phenotypes, which evoke either proinflammatory or neuroprotective responses. Given the association of microglia with the pathogenesis of neuronal diseases, they are in focus as therapeutic targets for the treatment of such conditions. Stem cell factor (SCF) is a ligand for the c-kit receptor, one of the differentiation factors for bone marrow cells. In this study, characteristics of SCF-activated microglia and their effects on neurons were analyzed to investigate the therapeutic potential of SCF in neuronal diseases. SCF was found to induce proliferation, migration, and phagocytosis of microglia. In addition, SCF-derived microglia showed a neuroprotective phenotype expressing anti-inflammatory cytokines, growth factors, and M2 markers as compared to the phenotype shown by granulocyte macrophage-colony stimulating factor-derived microglia expressing inflammatory cytokines and M1 markers. Furthermore, supernatant medium from SCF-activated microglia enhanced cell proliferation and protection from cell death in NSC-34 neuronal cells. We conclude that SCF modulates microglial functions and induces activation of the neuroprotective effects of microglia, which could be used for treatment of neuronal diseases.

Terashima|Tomoya|T| Nakae|Yuki|Y| Katagi|Miwako|M| Okano|Junko|J| Suzuki|Yoshihisa|Y| Kojima|Hideto|H|


Percutaneous Reduction of a Dislocation of the Interphalangeal Joint of the Great Toe: A Case Report.

Abstract: Dorsal dislocation of the interphalangeal joint of the great toe is quite rare. Closed reduction is often attempted in the emergency setting, but this measure is seldom successful because of invagination of the sesamoid-plantar plate complex into the interphalangeal space. Generally, open reduction is indicated when closed reduction fails. In this report, percutaneous reduction of the incarcerated sesamoid was performed under local and intraarticular anesthesia at our outpatient clinic, leading to successful reduction.

Takeda|Shinsuke|S| Nishimura|Akinobu|A| Yamaji|Satoshi|S| Tabuchi|Akihiko|A| Sudo|Akihiro|A| Hirata|Hitoshi|H|

incarcerated sesamoid
great toe dislocation
sesamoid bone interposition


Acceleration of the Measurement Time of Thermopiles Using Sigma-Delta Control.

Abstract: This work presents a double sliding mode control designed for accelerating the measurement of heat fluxes using thermopiles. The slow transient response generated in the thermopile, when it is placed in contact with the surface to be measured, is due to the changes in the temperature distributions that this operation triggers. It is shown that under some conditions the proposed controls keep the temperature distribution of the whole system constant and that changes in the heat flux at the thermopile are almost instantaneously compensated by the controls. One-dimensional simulations and experimental results using a commercial thermopile, showing the goodness of the proposed approach, are presented. A first rigorous analysis of the control using the Sliding Mode Control and Diffusive Representation theories is also made.

thermopile
sigma-delta
sliding mode control
heat flux


Membrane and nuclear initiated estrogenic regulation of homeostasis.

Abstract: Reproduction and energy balance are inextricably linked in order to optimize the evolutionary fitness of an organism. With insufficient or excessive energy stores a female is liable to suffer complications during pregnancy and produce unhealthy or obesity-prone offspring. The quintessential function of the hypothalamus is to act as a bridge between the endocrine and nervous systems, coordinating fertility and autonomic functions. Across the female reproductive cycle various motivations wax and wane, following levels of ovarian hormones. Estrogens, more specifically 17β-estradiol (E2), coordinate a triumvirate of hypothalamic neurons within the arcuate nucleus (ARH) that govern the physiological underpinnings of these behavioral dynamics. Arising from a common progenitor pool of cells, this triumvirate is composed of the kisspeptin (Kiss1ARH), proopiomelanocortin (POMC), and neuropeptide Y/agouti-related peptide (AgRP) neurons. Although the excitability of these neuronal subpopulations is subject to genomic and rapid estrogenic regulation, kisspeptin neurons are the most sensitive, reflecting their integral function in female fertility. Based on the premise that E2 coordinates autonomic functions around reproduction, we will review the recent findings on the synaptic interactions between Kiss1, AgRP and POMC neurons and how the rapid membrane-initiated and intracellular signaling cascades activated by E2 in these neurons are critical for control of homeostatic functions supporting reproduction.

Stincic|Todd L|TL|
Rønnekleiv|Oline K|OK|
Kelly|Martin J|MJ|

Neuropeptide Y/agouti-related peptide neurons


Management of colorectal cancer during the COVID-19 pandemic: Recommendations from a statewide multidisciplinary cancer collaborative.

Abstract: COVID-19 has resulted in significant disruptions in cancer care. The Illinois Cancer Collaborative (ILCC), a statewide multidisciplinary cancer collaborative, has developed expert recommendations for triage and management of colorectal cancer when disruptions occur in usual care. Such recommendations would be applicable to future outbreaks of COVID-19 or other large-scale disruptions in cancer care.

COVID-19
access
colorectal neoplasms
evaluation
healthcare quality


Significant increase in prostatectomy and decrease in radiation for clinical T3 prostate cancer from 1998 to 2012.

Abstract:
PURPOSE
We aimed to describe changes in treatment patterns for clinical T3 prostate cancer (PCa) from 1998 to 2012, specifically investigating what factors influence receipt of prostatectomy or radiation.

MATERIALS AND METHODS
Using the Surveillance, Epidemiology, and End Results database, we studied 11,604 men with clinical T3N0M0 PCa from 1998 to 2012, with treatment categorized as radiation, radical prostatectomy (RP), or no curative therapy. We calculated rate of treatment type by year of diagnosis to investigate trends in treatment patterns, further stratifying by clinical T3a, defined as unilateral and bilateral extracapsular extension (n = 3,842), vs. T3b (defined as extension to seminal vesicles (n = 3,665). Finally, a multivariable logistic regression analysis measured association of demographic and clinical variables with type of treatment received for years 2010 to 2011.

RESULTS
Rates of prostatectomy increased significantly from 1998 to 2012 (12.5% vs. 44.4%), radiation decreased significantly (55.8% vs. 38.4%), and receipt of no treatment also decreased (31.7% vs. 17.2%, all P<0.001). These trends were similar for clinical T3a and T3b. Rates of prostatectomy surpassed radiation by 2008 in clinical T3a, reaching 49.8% vs. 37.1%, respectively, in 2012 (P = 0.002), and were statistically similar to radiation in 2012 for clinical T3b, reaching 41.6% vs. 42.1% (P = 0.92). Multivariable logistic regression analysis demonstrated that patients were less likely to receive prostatectomy than radiation if biopsy Gleason scores of 8 to 10 (adjusted odds ratio [AOR] = 0.41, 0.32-0.53), higher initial prostate-specific antigen (AOR = 0.97, 0.97-0.98), and older age (AOR = 0.92, 0.90-0.03, all P<0.01). The likelihood of RP was similar among cT3b vs. cT3a (AOR = 0.95, 0.71-1.26, P = 0.74).

CONCLUSIONS
Since 1998, there has been a significant increase in the use of RP for clinical T3 PCa and a significant decrease in the use of radiation such that in 2012, the use of prostatectomy exceeded the use of radiation.

Nezolosky|Michelle D|MD|
Dinh|Kathryn T|KT|
Muralidhar|Vinayak|V|
Mahal|Brandon A|BA|
Chen|Yu-Wei|YW|
Beard|Clair J|CJ|
Choueiri|Toni K|TK|
Martin|Neil E|NE|
Sweeney|Christopher J|CJ|
Trinh|Quoc-Dien|QD|
Nguyen|Paul L|PL|

Prostatectomy
Prostate cancer
Treatment patterns
Clinical T3 disease
Radiation therapy


A Hypericin Delivery System Based on Polydopamine Coated Cerium Oxide Nanorods for Targeted Photodynamic Therapy.

Abstract: Photodynamic therapy (PDT) as a non-aggressive therapy with fewer side effects has unique advantages over traditional treatments. However, PDT still has certain limitations in clinical applications, mainly because most photosensitizers utilized in PDT are hydrophobic compounds, which will self-aggregate in the aqueous phase and cause undesirable effects. In order to resolve this, we utilized the self-polymerization of dopamine molecules under alkaline conditions to coat cerium oxide nanorods (CeONR) with a dense polydopamine (PDA) film. Thereafter, thiolated galactose (Gal-SH) and hypericin (Hyp) were modified and loaded onto the surface to construct CeONR@PDA-Gal/Hyp, respectively, which can be used for targeted photodynamic therapy of human hepatoma HepG2 cells. CeONR@PDA-Gal/Hyp was characterized by transmission electron microscope (TEM), Zeta potential, Ultraviolet-visible (UV-Vis), and fluorescence spectroscopy, respectively. This hypericin delivery system possesses good biocompatibility and specific targeting ability, where the galactose units on the surface of CeONR@PDA-Gal/Hyp can specifically recognize the asialo-glycoprotein receptors (ASGP-R), which overexpress on HepG2 cell membrane. Furthermore, Hyp will detach from the surface of CeONR@PDA-Gal/Hyp after the nanorods enter cancer cells, and shows excellent PDT effect under the irradiation of light with a wavelength of 590 nm. Our work exemplifies a novel targeted delivery of hydrophobic photosensitizers for cancer treatment.

Wang|Yang|Y| Zhang|Yu|Y| Jin|Ming|M| Lv|Yinghua|Y| Pei|Zhichao|Z| Pei|Yuxin|Y|

hypericin
polydopamine
cerium oxide nanorods
photodynamic therapy
targeted delivery


Spirometric and hygienic criteria in recognition of occupational COPD in Poland - A retrospective analysis of medical records.

Abstract:
OBJECTIVES
Chronic obstructive pulmonary disease (COPD) may be work-related. It has been estimated that 15% of the population burden of COPD is attributable to occupational exposure. However, in Poland COPD is rarely recognized as an occupational disease. The aim of the study has been to analyze the causes of the low prevalence of work-related COPD in the context of the existing criteria as well as to analyze which part of the assessment - clinical or hygienic one - is responsible for such a low rate of occupational COPD recognitions.

MATERIAL AND METHODS
The study group included 150 patients hospitalized with a suspicion of occupational COPD. Each patient underwent a clinical examination, spirometry and reversibility test using bronchodilator. Moreover, hygienic evaluation of work conditions was performed in all the considered cases.

RESULTS
In the case of the patients who fulfilled the criteria for COPD diagnosis in accordance with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) occupational origins of the disease, the disease was not recognized because 24.1% of the individuals did not meet spirometric criteria included in a definition of COPD in the Polish list of occupational diseases, while 27.8% of the individuals did not fulfill the criterion of a documented exposure to dusts and irritant gases. None of these criteria was fulfilled by 42.6% of the patients.

CONCLUSIONS
In our country, both clinical and hygienic criteria result in limitations in recognition of occupational COPD. There is the need to establish new guidelines for the recognition of COPD as a compensable disease in Poland. Int J Occup Med Environ Health 2018;31(2):139-150.

Kleniewska|Aneta|A| Walusiak-Skorupa|Jolanta|J| Lipińska-Ojrzanowska|Agnieszka|A| Szcześniak|Kamila|K| Wiszniewska|Marta|M|

D029424:Pulmonary Disease, Chronic Obstructive

occupational
COPD
chronic obstructive pulmonary disease
compensation
VGDF
acknowledgement of occupational disease


New carboxysilane-coated iron oxide nanoparticles for nonspecific cell labelling.

Abstract: Magnetic resonance imaging (MRI) offers the possibility of tracking cells labelled with a contrast agent and evaluating the progress of cell therapies. This requires efficient cell labelling with contrast agents. A basic incubation of cells with iron oxide nanoparticles (NPs) is a common method. This study reports the synthesis at the gram scale of iron oxide nanoparticles as MRI T₂ contrast agents for cell labelling. These NPs are based on small iron oxide cores coated with a thin polysiloxane shell presenting carboxylic acid functions. The iron oxide cores produced have been characterized by transmission electron microscopy, X-ray diffraction, ζ-potential, infrared, photon correlation spectroscopy, atomic force microscopy, magnetometry and relaxometric measurements. These measurements confirmed the expected surface modification by carboxysilane. Carboxylic groups created electrostatic repulsion between NPs when they are deprotonated. Therefore, highly concentrated aqueous solutions of carboxysilane coated iron oxide NPs can be obtained, up to 70% (w/w). These NPs could be used for cell labelling owing to their aggregation and re-dispersion properties. NPs precipitated in Dulbecco's modified Eagle medium induced a rapid association with 3 T6 fibroblast cells and could easily be re-dispersed in phosphate buffer saline solution to obtain properly labelled cells.

Bridot|Jean-Luc|JL|
Stanicki|Dimitri|D|
Laurent|Sophie|S|
Boutry|Sébastien|S|
Gossuin|Yves|Y|
Leclère|Philippe|P|
Lazzaroni|Roberto|R|
Vander Elst|Luce|L|
Muller|Robert N|RN|

iron oxide
nanoparticles
cell labelling
contrast agent
colloidal stability
ferrofluids
silane


Landmark papers on the discovery of methotrexate for the treatment of rheumatoid arthritis and other systemic inflammatory rheumatic diseases: a fascinating story.

Abstract: This review highlights the story of how methotrexate (MTX), a drug discovered for the treatment of childhood leukemia, became the mainstay of treatment and the standard-of-care for rheumatoid arthritis (RA) and was also found useful for several additional related rheumatological diseases. As against several synthetic disease-modifying antirheumatic drugs (csDMARDs) for treating RA that were discovered serendipitously, the use of low-dose MTX (LD-MTX) was based on sound reasoning and astute observations made in the 1940s and 1950s. The difference between high-dose MTX (HD-MTX) used in the treatment of childhood leukaemia and other malignancies as against LD-MTX used in rheumatology is emphasized.

landmark papers
discovery
rheumatoid arthritis
historical
low-dose methotrexate


Outer membrane protein OmpU is related to iron balance in Vibrio alginolyticus.

Abstract: Outer membrane protein U (OmpU) is a major porin from Vibrio alginolyticus and has been considered a vaccine candidate against infection by V. alginolyticus. After pre-incubated with polyclonal antibody against rOmpU, V. alginolyticus showed a 78% decrease in extracellular iron level, suggesting that interruption of OmpU could increase intracellular iron level. The mRNA expression of ompU under iron-limited conditions was determined using real-time reverse transcriptase PCR. The mRNA level of ompU was downregulated to 0.27-, 0.036- and 0.019-fold after the addition of the iron chelator 2,2'-bipyridyl for 10, 30 and 60 min, respectively. In addition, the promoter of ompU contained a ferric uptake regulator (Fur) binding site, which revealed the potential regulation of ompU by Fur and iron. Fur from V. alginolyticus was purified and used for electrophoretic mobility shift assay. The result showed that in the absence of Fe2+, purified recombinant Fur could specifically bind to the promoter DNA of ompU, while in the presence of Fe2+, the binding of Fur and the promoter DNA was suppressed. Our study preliminarily explored the function of OmpU in iron balance in V. alginolyticus, and these findings were helpful in understanding iron metabolism in V. alginolyticus.

Lv|Tengteng|T| Dai|Fa|F| Zhuang|Qiuting|Q| Zhao|Xuelin|X| Shao|Yina|Y| Guo|Ming|M| Lv|Zhimeng|Z| Li|Chenghua|C| Zhang|Weiwei|W|

D001425:Bacterial Outer Membrane Proteins

D015964:Gene Expression Regulation, Bacterial


Determinants of nurse job dissatisfaction - findings from a cross-sectional survey analysis in the UK.

Abstract:
Background
A lower recruitment and high turnover rate of registered nurses have resulted in a global shortage of nurses. In the UK, prior to the COVID-19 epidemic, nurses' intention to leave rates were between 30 and 50% suggesting a high level of job dissatisfaction.

Methods
In this study, we analysed data from a cross-sectional mixed-methods survey developed by the Royal College of Nursing and administered to the nursing workforce across all four UK nations, to explore the levels of dissatisfaction and demoralisation- one of the predictors of nurses' intention to leave. We carried out logistic regression analysis on available data in order to determine what impacts job dissatisfaction.

Results
In total, 1742 nurses responded to questions about working conditions on their last shift. We found that nearly two-thirds of respondents were demoralised. Nurses were five times more likely (OR 5.08, 95% CI: 3.82-6.60) to feel demoralised if they reported missed care. A perceived lack of support had nearly the same impact on the level of demoralisation (OR 4.8, 95% CI: 3.67-6.38). These findings were reflected in the qualitative findings where RNs reported how staffing issues and failures in leadership, left them feeling disempowered and demoralised.

Conclusion
A large proportion of nurses reported feeling dissatisfied and demoralised. In order to reduce the negative impact of dissatisfaction and improve retention, more research needs to investigate the relationship dynamics within healthcare teams and how the burden experienced by RNs when unsupported by managers impacts on their ability to provide safe, good-quality care. These findings predate the current Covid-19 pandemic outbreak which may have had a further detrimental effect on job satisfaction in the UK and other nation's nursing workforce.

Senek|Michaela|M|0000-0003-4226-2220 Robertson|Steven|S| Ryan|Tony|T| King|Rachel|R| Wood|Emily|E| Taylor|Bethany|B| Tod|Angela|A|

UK
Intention to leave
Missed care
Staffing issues
Leadership
Nurse job satisfaction


A Combination Therapy with Baicalein and Taxol Promotes Mitochondria-Mediated Cell Apoptosis: Involving in Akt/β-Catenin Signaling Pathway.

Abstract: Baicalein, a major flavonoid, possesses anticancer and anti-inflammatory activity. The aim of the study is to explore the efficiency of combination therapy with baicalein and taxol, as well as the molecular mechanism on antitumor activity. Human ovarian cancer cells were treated with different concentration of baicalein for 48 h, and cell viability was determined by MTT assay. Baicalein inhibited cell proliferation of ovarian cancer cells, and IC50 value of baicalein in A2780 cells, SKOV3 cells, and OVCAR cells was 46.23, 60.68, and 38.03 μM, respectively. The ovarian cancer cells were treated with 10 μM of baicalein combined with increasing concentration of taxol for 48 h, and the results demonstrated that combination therapy with baicalein and taxol had much higher antitumor effects compared with the monotherapy. The molecular mechanisms involving in combination therapy promoted the caspase-3 activity then leading to cleavage of poly-ADP-ribose polymerase, which increased the cell apoptosis of ovarian cancer cells. Moreover, Z-VAD-FMK treatment partially decreased the baicalein-induced proliferation inhibition in human ovarian cancer cells. Furthermore, baicalein induced apoptosis through activation of the activities of caspase-3,-9, and increased cytoplasmic cytochrome C release. Importantly, baicalein inhibited the growth of A2780 cells by inhibiting Akt/β-catenin signaling pathway. In conclusion, our result revealed that baicalein combinated with taxol at low concentrations could exert synergistic antitumor effects in ovarian cancer cells through mitochondria-mediated cell apoptosis and Akt/β-catenin signaling pathway. Baicalein has a promising potential to be developed as an antitumor compound, and combination therapy of baicalein and taxol exhibits an antitumor potential in clinical therapy for human ovarian cancers.

Pan|Qiong|Q| Xue|Min|M| Xiao|Song-Shu|SS| Wan|Ya-Jun|YJ| Xu|Da-Bao|DB|

combination therapy
synergistic
necrosis


Monoclonal antibodies for differentiating infections of three serological-related tospoviruses prevalent in Southwestern China.

Abstract:
BACKGROUND
The thrips-borne tospoviruses Calla lily chlorotic spot virus (CCSV), Tomato zonate spot virus (TZSV) and a new species provisionally named Tomato necrotic spot associated virus (TNSaV) infect similar crops in southwestern China. The symptoms exhibiting on virus-infected crops are similar, which is difficult for distinguishing virus species by symptomatology. The sequences of nucleocapsid proteins (NPs) of CCSV, TNSaV and TZSV share high degrees of amino acid identity with each other, and their serological relationship was currently demonstrated from the responses of the previously reported monoclonal antibodies (MAbs) against the NP of CCSV (MAb-CCSV-NP) and the nonstructural NSs protein of Watermelon silver mottle virus (WSMoV) (MAb-WNSs). Therefore, the production of virus-specific antibodies for identification of CCSV, TNSaV and TZSV is demanded to improve field surveys.

METHODS
The NP of TZSV-13YV639 isolated from Crinum asiaticum in Yunnan Province, China was bacterially expressed and purified for producing MAbs. Indirect enzyme-linked immunosorbent assay (ELISA) and immunoblotting were conducted to test the serological response of MAbs to 18 tospovirus species. Additionally, the virus-specific primers were designed to verify the identity of CCSV, TNSaV and TZSV in one-step reverse transcription-polymerase chain reaction (RT-PCR).

RESULTS
Two MAbs, denoted MAb-TZSV-NP(S15) and MAb-TZSV-NP(S18), were screened for test. MAb-TZSV-NP(S15) reacted with CCSV and TZSV while MAb-TZSV-NP(S18) reacted specifically to TZSV in both indirect ELISA and immunoblotting. Both MAbs can be used to detect TZSV in field-collected plant samples. The epitope of MAb-TZSV-NP(S18) was further identified consisting of amino acids 78-86 (HKIVASGAD) of the TZSV-13YV639 NP that is a highly conserved region among known TZSV isolates but is distinct from TNSaV and TZSV.

CONCLUSIONS
In this study, two MAbs targeting to different portions of the TZSV NP were obtained. Unlike MAb-CCSV-NP reacted with TNSaV as well as CCSV and TZSV, both TZSV MAbs can be used to differentiate CCSV, TNSaV and TZSV. The identity of CCSV, TNSaV and TZSV was proven by individual virus-specific primer pairs to indicate the correctness of serological responses. We also proposed an serological detection platform using MAb-CCSV-NP, MAb-TZSV-NP(S15) and MAb-TZSV-NP(S18) to allow researchers and quarantine staff to efficiently diagnose the infections of CCSV, TNSaV and TZSV in China and other countries.

Chen|Yu-Han|YH| Dong|Jiahong|J| Chien|Wan-Chu|WC| Zheng|Kuanyu|K| Wu|Kuo|K| Yeh|Shyi-Dong|SD| Sun|Jing-Hua|JH| Wang|Yun-Chi|YC| Chen|Tsung-Chi|TC|

Monoclonal antibody
Tospovirus
Quarantine
Diagnosis
Serological assay


Autophagy suppresses host adaptive immune responses toward Borrelia burgdorferi.

Abstract: We have previously demonstrated that inhibition of autophagy increased the Borrelia burgdorferi induced innate cytokine production in vitro, but little is known regarding the effect of autophagy on in vivo models of Borrelia infection. Here, we showed that ATG7-deficient mice that were intra-articular injected with Borrelia spirochetes displayed increased joint swelling, cell influx, and enhanced interleukin-1β and interleukin-6 production by inflamed synovial tissue. Because both interleukin-1β and interleukin-6 are linked to the development of adaptive immune responses, we examine the function of autophagy on Borrelia induced adaptive immunity. Human peripheral blood mononuclear cells treated with autophagy inhibitors showed an increase in interleukin-17, interleukin-22, and interferon-γ production in response to exposure to Borrelia burgdorferi. Increased IL-17 production was dependent on IL-1β release but, interestingly, not on interleukin-23 production. In addition, cytokine quantitative trait loci in ATG9B modulate the Borrelia induced interleukin-17 production. Because high levels of IL-17 have been found in patients with confirmed, severe, chronic borreliosis, we propose that the modulation of autophagy may be a potential target for anti-inflammatory therapy in patients with persistent Lyme disease.

Buffen|Kathrin|K|
Oosting|Marije|M|
Li|Yang|Y|
Kanneganti|Thirumala-Devi|TD|
Netea|Mihai G|MG|
Joosten|Leo A B|LA|


Human epidermal growth factor antagonists and cardiotoxicity-A short review of the problem and preventative measures.

Abstract: The Human Epidermal growth factor Receptor 2 (HER2) is a potent mediator of cellular growth and proliferation. It plays an important role in cardiac development and maintaining the physiologic function of an adult heart. Amplification of the HER2 gene, and the corresponding overexpression of the HER2 receptor, occurs in roughly 20% of breast tumors and is associated with a poor outcome. Molecular targeting of the HER2 receptor with the humanized monoclonal antibody, Trastuzumab has improved disease-free and overall survival in patients with both metastatic and early HER2-positive breast cancer. Although trastuzumab is devoid of the classical toxicities associated with chemotherapy, one of the major concerns noted is the occurrence of symptomatic and asymptomatic cardiotoxicity (decline in left-ventricular-ejection-fraction (LVEF). Additionally, newer HER2 therapies such as Lapatinib, Pertuzumab and Ado-trastuzumab (TDM1) are either approved or are being evaluated in clinical trials for cancer therapy. Targeted therapies against HER2 have led to revolutionary strides in breast cancer research and treatment. With the concern of cardiotoxicity caused by these agents, new treatment strategies for preventing cardiac side effects need to be developed. In this review, we discuss the proposed mechanisms of HER 2 antagonist-induced cardiotoxicity and the ways to prevent it.

Dias|A|A|
Claudino|W|W|
Sinha|R|R|
Perez|C A|CA|
Jain|D|D|

D000970:Antineoplastic Agents
D001943:Breast Neoplasms
D066126:Cardiotoxicity
D004815:Epidermal Growth Factor
D006801:Humans
D015398:Signal Transduction

Left ventricular ejection fraction (LVEF)


Clinical implications of pathologic factors after thyroid lobectomy in patients with papillary thyroid carcinoma.

Abstract:
OBJECTIVE
We evaluated the clinical and prognostic significance of pathologic factors by analyzing the treatment results of patients who underwent thyroid lobectomy.

MATERIALS AND METHODS
We retrospectively analyzed data from 734 patients diagnosed with papillary thyroid cancer who underwent thyroid lobectomy at Korea University Hospital from January 2004 to December 2016.

RESULTS
A total of 734 patients were included in the study and their mean age was 44.5 years (range, 15-83). On univariate analysis, tumor size and recurrence-free survival were significantly related. The 10-year recurrence-free survival was 98.3% for tumors ≤1cm, 77.8% for >1cm and ≤2cm, and 66.7% for >2cm (p = 0.014). Recurrence-free survival was significantly different between patients with and without microscopic extrathyroidal extension (p=0.002). The 10-year recurrence-free survival rate was 99.2% for patients without extrathyroidal extension and 92.2% for patients with microscopic extrathyroidal extension. Multivariate analysis showed only microscopic extrathyroidal extension was significantly correlated with recurrence-free survival (p=0.029).

CONCLUSION
In patients undergoing thyroid lobectomy for low-risk papillary thyroid cancer, microscopic extrathyroidal extension was an important prognostic factor associated with recurrence-free survival. However, in cases with microscopic extrathyroidal extension findings on postoperative pathologic examination, appropriate ultrasonographic follow-up of the contralateral thyroid lobe and cervical lymph node to facilitate early detection and prompt treatment of recurrence can control the disease without a deterioration of survival rate.

Park|Young Min|YM|
Lee|Doh Young|DY|
Oh|Kyung Ho|KH|
Cho|Jae-Gu|JG|
Baek|Seung-Kuk|SK|
Kwon|Soon-Young|SY|
Jung|Kwang-Yoon|KY|
Woo|Jeong-Soo|JS|

Pathologic factor
Thyroid lobectomy
Papillary thyroid carcinoma
Microscopic extrathyroidal extension
Recurrence


Antibacterial and Osteogenic Activity of Titania Nanotubes Modified with Electrospray-Deposited Tetracycline Nanoparticles.

Abstract: The nanotubular surface of titanium implants is known to have superior osteogenic activity but is also vulnerable to failure because of induced bacterial attachment and consequent secondary infection. Here, the problem was attempted to be solved by depositing nanosized tetracycline (TC)-loaded particles in poly(lactic-co-glycolic acid) on titania nanotubes (TNTs) using the electrospray deposition method. The antibacterial effect of the newly formed TNT surface was considered using the common pathogen Staphylococcus aureus. Maintenance of the biocompatibility and osteogenic characteristics of TNTs has been tested through cytotoxicity tests and osteogenic gene expression/extra-cellular matrix mineralization, respectively. The results showed that TNTs were successfully formed by anodization, and the characterization of TC deposited on the TNTs was controlled by varying the spraying parameters such as particle size and coating time. The TC nanoparticle-coated TNTs showed antibacterial activity against Staphylococcus aureus and biocompatibility with MC3T3-E1 pre-osteoblasts, while the osteogenic activity of the TNT structure was preserved, as demonstrated by osteocalcin and osteopontin gene expression, as well as Alizarin red staining. Hence, this study concluded that the electrosprayed TC coating of TNTs is a simple and effective method for the formation of bactericidal implants that can maintain osteogenic activity.

antibacterial
osteogenic activity
titania nanotubes
tetracycline
titanium
implants
electrospray deposition


'Laba' garlic processed by dense phase carbon dioxide: the relation between green colour generation and cellular structure, alliin consumption and alliinase activity.

Abstract:
BACKGROUND
'Laba' garlic is usually processed by soaking garlic in vinegar for more than 1 week during winter. It is popular for its unique green colour and tasty flavour. Greening is desirable and required for this product as its characteristic. Dense phase carbon dioxide (DPCD) had a significant effect on the greening of intact garlic (Allium sativum L.) cloves. The relation between green colour generation and alliin consumption, alliinase activity and the cellular structure of garlic, respectively, were investigated in this work. The effects of treatment time, pressure and temperature of DPCD were also analysed and discussed.

RESULTS
DPCD had a significant effect on the cellular structure of garlic cells. Garlic protoplast underwent greater morphological change after DPCD treatments at higher temperatures while the amount of precipitate increased with greater treatment time and temperature. Common trends on garlic greening and alliin consumption were observed except for DPCD treatment at 10 MPa and 65 °C. The alliinase activity decreased with increasing treatment time, pressure and temperature. It reached the lowest level at 13 MPa and 55 °C.

CONCLUSION
The formation of the green colour was a comprehensive result of DPCD on changing cellular structure, alliin consumption and alliinase activity. DPCD treatment at 10 MPa and 55 °C was the optimum condition for the greening of 'Laba' garlic. This work further facilitated the application of DPCD in the industrial production of 'Laba' garlic. © 2015 Society of Chemical Industry.

Tao|Dandan|D| Zhou|Bing|B| Zhang|Luyao|L| Hu|Xiaosong|X| Liao|Xiaojun|X| Zhang|Yan|Y|

D002245:Carbon Dioxide
D013437:Carbon-Sulfur Lyases
D011232:Chemical Precipitation
D002681:China
D018556:Crops, Agricultural
D003545:Cysteine
D005520:Food Preservatives
D063427:Food Quality
D061353:Food Storage
D057141:Food, Preserved
D005737:Garlic
D006358:Hot Temperature
D008855:Microscopy, Electron, Scanning
D010860:Pigments, Biological
D010940:Plant Proteins
D018517:Plant Roots
D011312:Pressure
D011523:Protoplasts
D012034:Refrigeration
D013997:Time Factors

alliin consumption
alliinase activity
DPCD
garlic greening
SEM analysis


Menstrual Pattern following Tubal Ligation: A Historical Cohort Study.

Abstract:
BACKGROUND
Tubal ligation (TL) is recommended for women who have completed their family planning. The existence of the menstrual disorders following this procedure has been the subject of debate for decades. This study was conducted to identify the relationship between tubal ligation and menstrual disorders.

MATERIALS AND METHODS
A historical cohort study was carried out on 140 women undergoing tubal ligation (TL group) and on 140 women using condom as the main contraceptive method (Non-TL group). They aged between 20 and 40 years and were selected from a health care center in Rudsar, Guilan Province, Iran, during 2013-2014. The two groups were comparable in demographic characteristics, obstetrical features and menstrual bleeding pattern using a routine questionnaire. A validated pictorial blood loss assessment chart (PBLAC) was also used to measure the menstrual blood loss.

RESULTS
Women with TL had more menstrual irregularity than those without TL (24.3 vs. 10%, P=0.002). Women with TL had more polymenorrhea (9.3 vs. 1.4%, P=0.006), hypermenorrhea (12.1 vs. 2.1%, P=0.002), menorrhagia (62.9 vs. 22.1%, P<0.0001) and menometrorrhagia (15.7 vs. 3.6%, P=0.001) than those without TL. There is a significant difference in the PBLAC score between women with and without TL (P<0.0001). According to logistic regression, age odds ratio [(OR=1.08, con- fidence interval (CI):1.07-1.17, P=0.03)], TL (OR=5.95, CI:3.45-10.26, P<0.0001) and cesarean section (OR=2.72, CI:1.49-4.97, P=0.001) were significantly associated with menorrhagia.

CONCLUSION
We found significant differences in menstrual disorders between women with and without TL. Therefore, women should be informed by the health providers regarding the advantages and disadvantages of TL before the procedures.

Sadatmahalleh|Shahideh Jahanian|SJ|
Ziaei|Saeideh|S|
Kazemnejad|Anoshirvan|A|
Mohamadi|Eesa|E|

Tubal Ligation
Historical Cohort Study
Menstrual Disorders
Pictorial Blood Loss Assessment Chart