BIRC7 promotes epithelial-mesenchymal transition and metastasis in papillary thyroid carcinoma through restraining autophagy.

Abstract: Papillary thyroid carcinoma (PTC) is the most common cancer of the endocrine system, which is usually associated with a favorable therapeutic response and prognosis. However, metastatic spreading occurs in around 5% of the PTC patients. Identification of molecular markers could early predict the metastatic potential, which is essential for reducing the patient's overtreatment. Baculoviral IAP Repeat Containing 7 (BIRC7) is an inhibitor of apoptosis protein (IAP) family gene that is known to be linked to tumor progression, but its role in the setting of PTC metastasis remains unknown. This study, therefore, aims to explore the role of BIRC7 in the metastasis and autophagy of PTC and elucidate its underlying molecular mechanisms. BIRC7 expression was assessed in fresh samples of human PTC and normal tissues via qRT-PCR and immunohistochemistry. In addition, BIRC7 was overexpressed and silenced in PTC cell lines followed by transmission electron microscopy, western blotting, immunofluorescence microscopy, wound healing and invasion assays. We further explored the relevance of BIRC7 in vivo using a tumor xenograft model. Our results demonstrated that BIRC7 plays a pro-invasive role in PTC. BIRC7 expression is significantly upregulated in PTC compared with matched thyroid normal tissues. In addition, we found that BIRC7 knockdown induced a significant reduction in PTC cell EMT and metastasis in vitro and in vivo, while overexpression of BIRC7 markedly enhanced PTC cell migration and invasion. Moreover, our data showed that BIRC7 was able to suppress autophagy through modulating the expression of ATG5 and BECN1, and that this suppression is responsible for BIRC7 silence induced suppression of EMT and metastasis of PTC cell. We further found that targeting both BIRC7 and mTOR enhances autophagy in PTC cells and to achieve synergistic antimetastatic efficacy in vitro and in vivo. These findings indicate that the suppression of autophagy by BIRC7 drives the invasion and metastasis of PTC cells, thus suggesting that the activation of autophagy may inhibit metastasis of PTC with high BIRC7 expression.

Liu|Kunpeng|K| Yu|Qingan|Q| Li|Hao|H| Xie|Changming|C| Wu|Yaohua|Y| Ma|Dakun|D| Sheng|Ping|P| Dai|Wenjie|W| Jiang|Hongchi|H|

BIRC7
metastasis
papillary thyroid carcinoma
autophagy
EMT


The yield of chromosomal microarray in pregnancies with congenital cardiac defects and normal noninvasive prenatal screening.

Abstract:
BACKGROUND
Evidence comparing the yield of chromosomal microarray analysis to noninvasive prenatal screening in pregnancies with congenital heart anomalies is currently limited.

OBJECTIVE
This study aimed to examine the residual risk of clinically significant chromosomal microarray analysis results in fetuses with congenital heart defects by its various subtypes following a normal noninvasive prenatal screening.

STUDY DESIGN
Using a population-based, countrywide computerized database, we retrieved the reports of all pregnancies undergoing chromosomal microarray analysis because of congenital heart defects through the years 2013-2019. We examined the risk of clinically significant (pathogenic and likely pathogenic) chromosomal microarray analysis results and compared it with the results of a local cohort of low-risk pregnancies. Of 5541 fetuses, 78 (1.4%) showed abnormal results. The residual risk of abnormal chromosomal microarray analysis results was calculated using several options-trisomies 21, 18, and 13; sex chromosome aneuploidies; 22q11.2 deletion, and deletions and duplications of at least 10 MB in size (genome-wide noninvasive prenatal screening)-following the exclusion of theoretically detectable noninvasive prenatal screening anomalies.

RESULTS
Of the 1728 fetuses with congenital heart defects, 93 (5.4%) showed clinically significant chromosomal microarray analysis results (relative risk, 2.7; 95% confidence interval, 2.3-3.1). The result of pregnancies with fetuses with congenital heart defects was compared with the results of the control population. Unique variants were found in 15 pregnancies (16.1%). The detection rate of noninvasive prenatal screening in isolated congenital heart defects varied from 1.0% (aimed at 3 common trisomies) to 2.2% (aimed at 5 common aneuploidies and 22q11.2 deletion) using noninvasive prenatal screening. In nonisolated congenital heart defects, the noninvasive prenatal screening detection rates ranged from 7.8% (aimed at common autosomal trisomies) to 9.2% using genome-wide noninvasive prenatal screening. The residual risk of clinically significant chromosomal microarray analysis results following normal noninvasive prenatal screening ranged from 2.0% to 2.8% in isolated congenital heart defects and 4.5% to 5.9% in nonisolated cases and was significantly higher than those of the control cohort in all noninvasive prenatal screening options. In addition, the residual risk following noninvasive prenatal screening aimed at chromosomes 13, 18, 21, X, and Y was significantly higher than those of the control cohort for most specific congenital heart defect subtypes, except for ventricular septal defects and aberrant right subclavian artery.

CONCLUSION
The residual risk of clinically significant chromosomal microarray analysis results in pregnancies with fetuses with congenital heart defects following normal noninvasive prenatal screening was higher than those in pregnancies with normal ultrasound in most isolated and nonisolated congenital heart defect subtypes. This information should be taken into account by obstetricians and genetic counselors when considering the option of diagnostic testing.

Sagi-Dain|Lena|L| Singer|Amihood|A| Segel|Reeval|R| Berger|Racheli|R| Kanengisser-Pines|Bibi|B| Maya|Idit|I|

chromosomal microarray
noninvasive prenatal screening
congenital heart defects
chromosomal aberrations


Patterns of DSM-5 posttraumatic stress disorder and depression symptoms in an epidemiological sample of Chinese earthquake survivors: A latent profile analysis.

Abstract:
BACKGROUND
Posttraumatic stress disorder (PTSD) and depression are highly comorbid in association with serious clinical consequences. Nevertheless, to date, no study using latent class or latent profile analysis (LCA/LPA) has examined patterns of co-occurring PTSD and depression symptoms among natural disaster survivors, nor has the distinctiveness of DSM-5 PTSD and depression symptoms been clarified in the aftermath of trauma. This study was primarily aimed at filling these gaps.

METHODS
LPA was used to examine self-reported PTSD and depression symptoms in an epidemiological sample of 1196 Chinese earthquake survivors.

RESULTS
A 4-class solution characterized by low symptoms (53.9%), predominantly depression (18.2%), predominantly PTSD (18.9%) and combined PTSD-depression (9.0%) patterns fit the data best. Demographic characteristics and earthquake-related exposures were specifically or consistently associated with the non-parallel profiles varying in physical health impairment.

LIMITATIONS
A sample exposed to specific traumatic events was assessed by self-report measures.

CONCLUSIONS
The distinctiveness of DSM-5 PTSD and depression symptoms following an earthquake suggests that PTSD and depression may be independent sequelae of psychological trauma rather than a manifestation of a single form of psychopathology. The current findings support the distinction between PTSD and depression constructs, and highlight the need for identifications of natural disaster survivors at high risk for PTSD and/or depression, and interventions individually tailored to one's symptom presentations.

Cao|Xing|X|
Wang|Li|L|
Cao|Chengqi|C|
Zhang|Jianxin|J|
Liu|Ping|P|
Zhang|Biao|B|
Wu|Qi|Q|
Zhang|Hong|H|
Zhao|Zhihong|Z|
Fan|Gaolin|G|
Elhai|Jon D|JD|

DSM-5
Posttraumatic stress disorder
Depression
Latent profile analysis
Natural disaster


Salvage pulmonary thromboembolectomy for massive pulmonary embolism in a child presented with syncope and subsequent cardiac arrest.

Abstract: Pulmonary embolism is frequently under-recognised in children and, therefore, a high index of suspicion should be exerted on patients with exertional dyspnoea, presyncope/syncope and unexplained cardiopulmonary arrest. We discuss a 10-year-old previously healthy girl who presented with syncope and subsequent cardiac arrest related to massive pulmonary embolism and was salvaged successfully by emergent pulmonary embolectomy.

Ak|Koray|K| Birkan|Yasar|Y| Akalın|Figen|F| Günay|Deniz|D|

Massive pulmonary embolism
cardiac arrest
embolectomy
adolescent


Improvement of symptoms in clinically suspect arthralgia and resolution of subclinical joint inflammation: a longitudinal study in patients that did not progress to clinical arthritis.

Abstract:
INTRODUCTION
Arthralgia and MRI-detected subclinical inflammation can precede the development of clinically evident rheumatoid arthritis (RA). However, part of the patients presenting with clinically suspect arthralgia (CSA) do not progress to RA. In these 'non-progressors', we aimed to study the frequencies of spontaneous improvement of arthralgia and its relation with the course of subclinical inflammation.

METHODS
Between April 2012 and April 2015, 241 patients were considered at risk for RA based on the clinical presentation and included in the CSA cohort. One hundred fifty-two patients with complete data on clinical follow-up did not develop clinical arthritis, of which 98 underwent serial 1.5T MRI scans (wrist, MCP2-5, and MTP1-5 joints) at baseline and after 2 years. MRI scans were scored for synovitis, tenosynovitis, and bone marrow oedema (summed: MRI inflammation score). MRI scores were compared to scores of symptom-free persons.

RESULTS
After a 2-year follow-up, 33% of the 'non-progressors' had complete resolution of symptoms; 67% had no symptom resolution and were diagnosed as persistent CSA (44%), osteoarthritis (10%), and tendinomuscular complaints (13%). With symptom-free controls as a reference, patients without resolution did not have increased MRI scores at any time point. However, patients achieving resolution of symptoms had increased MRI inflammation scores at baseline (4.0 vs. 2.6, p = 0.037), but not after 2 years (3.0 vs. 2.6; p = 0.57), and during follow-up, their MRI inflammation score decreased significantly (p = 0.036).

CONCLUSIONS
A subgroup of CSA patients that did not progress to RA had spontaneous improvement of symptoms and resolution of subclinical joint inflammation. This time relationship suggests that symptoms and inflammation were causally related in these patients. Further research is needed to identify the mechanisms underlying the resolution of inflammation.

Rheumatoid arthritis
Clinical research
Imaging
Outcome measures


Trading direct for indirect defense? Phytochrome B inactivation in tomato attenuates direct anti-herbivore defenses whilst enhancing volatile-mediated attraction of predators.

Abstract: Under conditions of competition for light, which lead to the inactivation of the photoreceptor phytochrome B (phyB), the growth of shade-intolerant plants is promoted and the accumulation of direct anti-herbivore defenses is down-regulated. Little is known about the effects of phyB on emissions of volatile organic compounds (VOCs), which play a major role as informational cues in indirect defense. We investigated the effects of phyB on direct and indirect defenses in tomato (Solanum lycopersicum) using two complementary approaches to inactivate phyB: illumination with a low red to far-red ratio, simulating competition, and mutation of the two PHYB genes present in the tomato genome. Inactivation of phyB resulted in low levels of constitutive defenses and down-regulation of direct defenses induced by methyl jasmonate (MeJA). Interestingly, phyB inactivation also had large effects on the blends of VOCs induced by MeJA. Moreover, in two-choice bioassays using MeJA-induced plants, the predatory mirid bug Macrolophus pygmaeus preferred VOCs from plants in which phyB was inactivated over VOCs from control plants. These results suggest that, in addition to repressing direct defense, phyB inactivation has consequences for VOC-mediated tritrophic interactions in canopies, presumably attracting predators to less defended plants, where they are likely to find more abundant prey.

Cortés|Leandro E|LE|
Weldegergis|Berhane T|BT|
Boccalandro|Hernán E|HE|
Dicke|Marcel|M|
Ballaré|Carlos L|CL|

D018506:Gene Expression Regulation, Plant

indirect defense
defense
phytochrome
volatile
tomato (Solanum lycopersicum)
jasmonate
tritrophic interaction
R : FR ratio


SARS-CoV-2-reactive interferon-γ-producing CD8+ T cells in patients hospitalized with coronavirus disease 2019.

Abstract: There is limited information on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) T-cell immune responses in patients with coronavirus disease 2019 (COVID-19). Both CD4+ and CD8+ T cells may be instrumental in resolution of and protection from SARS-CoV-2 infection. Here, we tested 25 hospitalized patients either with microbiologically documented COVID-19 (n = 19) or highly suspected of having the disease (n = 6) for presence of SARS-CoV-2-reactive CD69+ expressing interferon-γ (IFN-γ) producing CD8+ T cells using flow-cytometry for intracellular cytokine staining assay. Two sets of overlapping peptides encompassing the SARS-CoV-2 Spike glycoprotein N-terminal 1 to 643 amino acid sequence and the entire sequence of SARS-CoV-2 M protein were used simultaneously as antigenic stimulus. Ten patients (40%) had detectable responses, displaying frequencies ranging from 0.15 to 2.7% (median of 0.57 cells/µL; range, 0.43-9.98 cells/µL). The detection rate of SARS-CoV-2-reactive IFN-γ CD8+ T cells in patients admitted to intensive care was comparable (P = .28) to the rate in patients hospitalized in other medical wards. No correlation was found between SARS-CoV-2-reactive IFN-γ CD8+ T-cell counts and SARS-CoV-2 S-specific antibody levels. Likewise, no correlation was observed between either SARS-CoV-2-reactive IFN-γ CD8+ T cells or S-specific immunoglobulin G-antibody titers and blood cell count or levels of inflammatory biomarkers. In summary, in this descriptive, preliminary study we showed that SARS-CoV-2-reactive IFN-γ CD8+ T cells can be detected in a non-negligible percentage of patients with moderate to severe forms of COVID-19. Further studies are warranted to determine whether quantitation of these T-cell subsets may provide prognostic information on the clinical course of COVID-19.

Giménez|Estela|E|
Albert|Eliseo|E|
Torres|Ignacio|I|
Remigia|María José|MJ|
Alcaraz|María Jesús|MJ|
Galindo|María José|MJ|
Blasco|María Luisa|ML|
Solano|Carlos|C|
Forner|María José|MJ|
Redón|Josep|J|
Signes-Costa|Jaime|J|
Navarro|David|D|0000-0003-3010-4110


Internet-delivered cognitive behaviour therapy for depression in people with diabetes: study protocol for a randomised controlled trial.

Abstract:
INTRODUCTION
Depression substantially contributes to the personal burden and healthcare costs of living with diabetes mellitus (DM). Comorbid depression and DM are associated with poorer quality of life, poorer self-management and glycemic control, increased risk for DM complications and higher mortality rates, and higher health service utilization. Depression remains under-recognized and undertreated in people with DM, which may, in part, result from barriers associated with accessing face-to-face treatment. This study will examine the efficacy of an internet-based cognitive behaviour therapy programme for major depressive disorder (iCBT-MDD) in people with DM.

METHODS AND ANALYSIS
A CONSORT 2010 compliant, registered randomised controlled trial of the intervention (iCBT-MDD) versus a treatment as usual control group will be conducted. The study will include 100 adults aged 18 years and over with a diagnosis of type 1 or type 2 DM and self-reported symptoms that satisfy MDD which will enable us to detect a statistically significant difference with a group effect size of 0.6 at a power of 80% and significance level of p=0.05. Participants will be randomised to receive the iCBT-MDD programme immediately, or to wait 10 weeks before accessing the programme. Primary outcomes will be self-reported depression severity, DM-related distress, and glycemic control (glycosylated hemoglobin). Secondary outcomes will be general distress and disability, generalized anxiety, lifestyle behaviours, somatization, eating habits, alcohol use, and acceptability of the iCBT programme to participants, and practicality for clinicians. Data will be analyzed with linear mixed models for each outcome measure.

ETHICS AND DISSEMINATION
The Human Research Ethics Committee of St Vincent's Hospital Australia have given ethics approval (HREC/13/SVH/291). Results will be disseminated via peer-reviewed publication and social media channels of Australian Diabetes Consumer Representative Bodies.

TRIAL REGISTRATION NUMBER
The trial is registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12613001198718).

Robins|Lisa|L| Newby|Jill|J| Wilhelm|Kay|K| Smith|Jessica|J| Fletcher|Therese|T| Ma|Trevor|T| Finch|Adam|A| Campbell|Lesley|L| Andrews|Gavin|G|

Depression
Depressive and Affective Disorders
Internet


[Formula: see text] Reliable change in pediatric brain tumor: A preliminary investigation.

Abstract: Children treated for brain tumor show evidence of declines in general intellectual abilities (i.e., IQ). Group-level data indicate subtle declines over time on average, but no study has utilized a clinical criterion to identify and describe a reliable change in survivors of pediatric brain tumor (PBT). In this study, we discuss the utility of reliable change index (RCI) methodology to supplement group-level analysis (e.g., repeated measures ANOVA). This pilot sample consisted of 22 children (M age = 10.47 years) treated for PBT who completed initial and follow-up assessments (M interval = 23.58 months). Cognitive data included composite scores from the WISC-IV. An RCI z-score was calculated for each participant on each composite score based on two different test-retest reliability coefficients. As a group, survivors of PBT did not demonstrate a statistically significant change from initial to follow-up on any WISC-IV composite score. When RCI was calculated based on reliability coefficients with shorter test-retest intervals provided by the test publisher, 77% of survivors demonstrated a reliable change in performance on at least one measure. The frequency of RCI decreases in working memory was significantly higher than expected. In contrast, only 32% of survivors showed reliable changes on at least one measure when RCI was based on a reliability coefficient derived from a clinical sample with a longer retest interval. This study demonstrates that highly divergent results may be obtained with RCI and the importance of the source of reliability estimates.

Duda|Thomas A|TA|
Ris|M Douglas|MD|
Yeates|Keith Owen|KO|
Mahone|E Mark|EM|0000-0002-5022-1499
Haut|Jennifer S|JS|
Raghubar|Kimberly P|KP|

Pediatric
brain tumor
reliable change index
WISC
intelligence


Impact of body mass index on overall survival in patients with metastatic breast cancer.

Abstract:
BACKGROUND
High Body mass index (BMI) is a risk factor for breast cancer among postmenopausal women and an adverse prognostic factor in early-stage. Little is known about its impact on clinical outcomes in patients with metastatic breast cancer (MBC).

METHODS
The National ESME-MBC observational cohort includes all consecutive patients newly diagnosed with MBC between Jan 2008 and Dec 2016 in the 18 French comprehensive cancer centers.

RESULTS
Of 22 463 patients in ESME-MBC, 12 999 women had BMI data available at MBC diagnosis. Median BMI was 24.9 kg/m2 (range 12.1-66.5); 20% of women were obese and 5% underweight. Obesity was associated with more de novo MBC, while underweight patients had more aggressive cancer features. Median overall survival (OS) of the BMI cohort was 47.4 months (95% CI [46.2-48.5]) (median follow-up: 48.6 months). Underweight was independently associated with a worse OS (median OS 33 months; HR 1.14, 95%CI, 1.02-1.27) and first line progression-free survival (HR, 1.11; 95%CI, 1.01; 1.22), while overweight or obesity had no effect.

CONCLUSION
Overweight and obesity are not associated with poorer outcomes in women with metastatic disease, while underweight appears as an independent adverse prognostic factor.

Saleh|Khalil|K|
Carton|Matthieu|M|
Dieras|Véronique|V|
Heudel|Pierre-Etienne|PE|
Brain|Etienne|E|
D'Hondt|Véronique|V|
Mailliez|Audrey|A|
Patsouris|Anne|A|
Mouret-Reynier|Marie-Ange|MA|
Goncalves|Anthony|A|
Ferrero|Jean Marc|JM|
Petit|Thierry|T|
Emile|George|G|
Uwer|Lionel|L|
Debled|Marc|M|
Dalenc|Florence|F|
Jouannaud|Christelle|C|
Ladoire|Sylvain|S|
Leheurteur|Marianne|M|
Cottu|Paul|P|
Veron|Lucie|L|
Savignoni|Alexia|A|
Courtinard|Coralie|C|
Robain|Mathieu|M|
Delaloge|Suzette|S|
Deluche|Elise|E|

Overall survival
Metastatic breast cancer
BMI
Obesity
Underweight


Structural and Oxidation State Alternatives in Platinum and Palladium Complexes of a Redox-Active Amidinato Ligand.

Abstract: Reaction of [Pt(DMSO)2 Cl2 ] or [Pd(MeCN)2 Cl2 ] with the electron-rich LH=N,N'-bis(4-dimethylaminophenyl)ethanimidamide yielded mononuclear [PtL2 ] (1) but dinuclear [Pd2 L4 ] (2), a paddle-wheel complex. The neutral compounds were characterized through experiments (crystal structures, electrochemistry, UV-vis-NIR spectroscopy, magnetic resonance) and TD-DFT calculations as metal(II) species with noninnocent ligands L- . The reversibly accessible cations [PtL2 ]+ and [Pd2 L4 ]+ were also studied, the latter as [Pd2 L4 ][B{3,5-(CF3 )2 C6 H3 }4 ] single crystals. Experimental and computational investigations were directed at the elucidation of the electronic structures, establishing the correct oxidation states within the alternatives [PtII (L- )2 ] or [Pt. (L )2 ], [PtII (L0.5- )2 ]+ or [PtIII (L- )2 ]+ , [(PdII )2 (μ-L- )4 ] or [(Pd1.5 )2 (μ-L0.75- )4 ], and [(Pd2.5 )2 (μ-L- )4 ]+ or [(PdII )2 (μ-L0.75- )4 ]+ . In each case, the first alternative was shown to be most appropriate. Remarkable results include the preference of platinum for mononuclear planar [PtL2 ] with an N-Pt-N bite angle of 62.8(2)° in contrast to [Pd2 L4 ], and the dimetal (Pd2 4+ →Pd2 5+ ) instead of ligand (L- →L ) oxidation of the dinuclear palladium compound.

oxidation states
electron transfer
radical ligands
spectroelectrochemistry
spin distribution


Serologic responses to peptides of Anaplasma phagocytophilum and Borrelia burgdorferi in dogs infested with wild-caught Ixodes scapularis.

Abstract: Anaplasma phagocytophilum and Borrelia burgdorferi are both transmitted by Ixodes spp. and are associated with clinical illness in some infected dogs. This study evaluated canine antibody responses to the A. phagocytophilum p44 peptides APH-1 and APH-4 as well as the B. burgdorferi C6 peptide before and after doxycycline treatment. A total of eight dogs were infested with wild-caught I. scapularis for 1 week. Blood was collected prior to tick attachment and from Days 3-77 to 218-302 with doxycycline treatment beginning on Day 218. Blood was assayed for A. phagocytophilum DNA by PCR assay. Sera was assessed for antibodies by immunofluorescent antibody (IFA) test and ELISA. Anaplasma phagocytophilum DNA was amplified from blood of all dogs by Day 7. Antibodies to APH-4 were detected in serum as early as 14days after tick exposure and six dogs had APH-4 antibodies detected 3-7 days before antibodies against APH-1. All dogs were seropositive for A. phagocytophilum from Days 218 to 302. Antibodies to B. burgdorferi were detected in 6/8 dogs beginning 21days after I. scapularis infestation. Among the five dogs that remained seropositive at Day 218, C6 antibody levels declined on average 81% within 84days of initiating treatment. The results suggest that the APH-4 peptide may be more useful than APH-1 for detecting antibodies earlier in the course of an A. phagocytophilum infection. After doxycycline administration, C6 antibody levels but not APH-1 or APH-4 antibody levels decreased, suggesting a treatment effect on C6 antibody production.

Chandrashekar|R|R|
Beall|M J|MJ|
Thatcher|B|B|
Saucier|J M|JM|
Tyrrell|P|P|
Lappin|M R|MR|

D060888:Real-Time Polymerase Chain Reaction

Serology Antibody ELISA Lyme Quantitative


A proposal for field-level medical assistance in an international humanitarian response to chemical, biological, radiological or nuclear events.

Abstract: A capacity for field-level medical assistance for people exposed to chemical, biological, radiological or nuclear (CBRN) agents or medical support for people potentially exposed to these agents is intrinsically linked to the overall risk management approach adopted by the International Committee of the Red Cross (ICRC) for an international humanitarian response to a CBRN event. This medical assistance articulates: ▸the characteristics of the agent concerned (if known) ▸the need for immediate care particularly for people exposed to agents with high toxicity and short latency ▸the imperative for those responding to be protected from exposure to the same agents. This article proposes two distinct capacities for medical assistance--CBRN field medical care and CBRN first aid--that take the above into account and the realities of a CBRN event including the likelihood that qualified medical staff may not be present with the right equipment. These capacities are equally pertinent whether in support of ICRC staff or for assistance of victims of a CBRN event. Training of those who will undertake CBRN field medical care and CBRN first aid must include: ▸knowledge of CBRN agents, their impact on health and the corresponding toxidromes ▸skills to use appropriate equipment ▸use of appropriate means of self-protection ▸an understanding of the additional complexities brought by the need for and interaction of triage, transfer and decontamination. The development of CBRN field medical care and CBRN first aid continues within the ICRC while acknowledging that the opportunities for learning in real situations are extremely limited. Comments from others who work in this domain are welcome.

Malich|Gregor|G| Coupland|Robin|R| Donnelly|Steve|S| Baker|David|D|

D001694:Biological Warfare
D002618:Chemical Warfare
D004189:Disaster Planning
D004632:Emergency Medical Services
D006801:Humans
D009689:Nuclear Warfare
D012308:Risk Management


Inhibition of the nitric oxide/cyclic guanosine monophosphate pathway limited the cardioprotective effect of post-conditioning in hearts with apical myocardial infarction.

Abstract: Reperfusion damage involves opening of the mitochondrial permeability transition pore (mPTP) and loss of ATP synthesis. Several cardioprotective pathways are activated by ischemic or pharmacological post-conditioning (PC). The mechanisms that are activated by PC in no co-morbidity murine models include: activation of rescue kinases, oxidative stress reduction, glycolytic flux regulation and preservation of ATP synthesis. However, relatively scarce efforts have been made to define whether the efficacy of PC signaling is blunted by risk factors or systemic diseases associated with ischemic heart pathology. Experimental evidence has shown that the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling is a main mechanism activated by PC in hearts without pathological history. In this work we evaluated the participation of the NO pathway, through downstream kinase activation and inhibition of mPTP in hearts with previous infarct. Myocardial infarction was induced with a single dose of isoproterenol (85 mg/kg i.p.) to male Wistar rats. After 24 h, the hearts were mounted into the Langendorff system and subjected to 30 min of ischemia and 60 min of reperfusion. PC consisted of 5 cycles of 30 s of reperfusion/30 s of ischemia, then the hearts were reperfused with or without inhibitors of the NO/cGMP pathway. PC activates the NO/cGMP pathway, as increased cGMP and NO levels were detected in isoproterenol-treated hearts. The cardioprotective effect of PC was abolished with both L-NAME (inhibitor of constitutive NO synthase) and ODQ (inhibitor of soluble guanylate cyclase), whereas the NO donor (DETA-NO) restored cardioprotection even in the presence of L-NAME or ODQ. We also found that mitochondrial structure and function was preserved in PC hearts. We conclude that PC exerts cardioprotection in hearts with previous infarct by maintaining mitochondrial structure and function through NO-dependent pathway.

Correa|Francisco|F|
Buelna-Chontal|Mabel|M|
Chagoya|Victoria|V|
García-Rivas|Gerardo|G|
Vigueras|Rosa María|RM|
Pedraza-Chaverri|José|J|
García-Niño|Wylly Ramsés|WR|
Hernández-Pando|Rogelio|R|
León-Contreras|Juan Carlos|JC|
Zazueta|Cecilia|C|

D000818:Animals
D006157:Guanosine Monophosphate
D057775:Ischemic Postconditioning
D008297:Male
D008929:Mitochondria, Heart
D009203:Myocardial Infarction
D015428:Myocardial Reperfusion Injury
D019331:NG-Nitroarginine Methyl Ester
D009569:Nitric Oxide
D051381:Rats
D017208:Rats, Wistar
D015398:Signal Transduction

Post-conditioning
cGMP
Isoproterenol
Reperfusion injury


Multivisceral resection for locally advanced rectal cancer: adequate length of distal resection margin.

Abstract:
PURPOSE
Locally advanced rectal cancer may require an intraoperative decision regarding curative multivisceral resection (MVR) of adjacent organs. In bulky tumor cases, ensuring sufficient distal resection margin (DRM) for achievement of oncologic safety is very difficult. This study is designed to evaluate the adequate length of DRM in multiviscerally resected rectal cancer.

METHODS
A total of 324 patients who underwent curative low anterior resection for primary pT3-4 rectal cancer between 1995 and 2004 were identified from a prospectively collected colorectal database.

RESULTS
Short lengths of DRM (≤1 cm) did not compromise essentially poor oncologic outcomes in locally advanced rectal cancer (P = 0.736). However, especially in rectal cancers invading adjacent organs, DRM of less than 2 cm showed poor survival outcome. In 5-year and 10-year survival analysis of MVR, a shorter DRM (<2 cm) showed 41.9% and 30.5%, although a longer DRM (≥2 cm) showed 72.4% and 60.2% (P = 0.03, 0.044). In multivariate analysis of MVR, poorly differentiated histology, ulceroinfiltrative growth of tumor, and short DRM (<2 cm) were significant factors for prediction of poor survival outcome, although short DRM was not significantly related to local and systemic recurrence.

CONCLUSION
In locally advanced rectal cancer of pT3-4, a short length of DRM (≤1 cm) did not compromise essentially poor oncologic outcome. In rectal cancers invading adjacent organs and requiring MVR, a shorter DRM (<2 cm) was found to be related to poor survival outcome.

Kang|Hyo|H|
Kim|Ho Goon|HG|
Ju|Jae Kyun|JK|
Kim|Dong Yi|DY|

Multivisceral resection
Locally advanced rectal cancer
Distal resection margin


Unique presentation of cerebellopontine angle choroid plexus papillomas: case report and review of the literature.

Abstract: Objectives We present the case of a choroid plexus papilloma (CPP) in the cerebellopontine angle (CPA), describe the different appearances of CPPs with a variety of imaging techniques, and discuss the differential diagnosis of CPA tumors. Participant and Design We report the case of a 52-year-old woman with headache, tinnitus, and unilateral hearing impairment whose preoperative magnetic resonance imaging revealed a heterogeneously enhancing CPA mass that extended into the internal auditory canal. Main Outcome Measures, Results, and Conclusion The preoperative imaging appearance of the lesion was most consistent with that of a schwannoma. Postoperative histopathologic examination found the tumor to be a CPP with cuboidal epithelial cells overlying fibrovascular stroma. CPPs are rare benign central nervous system neoplasms arising from choroid plexus epithelium. The most common site of presentation is in the fourth ventricle in adults and the lateral ventricles in children. CPPs rarely occur in the CPA, and when they do, clinical-radiologic diagnosis is difficult due to both the rarity of this presentation and to nonspecific radiological features.

Anderson|Mark|M|
Babington|Parker|P|
Taheri|Reza|R|
Diolombi|Mairo|M|
Sherman|Jonathan H|JH|


Complement activation in patients with immune thrombocytopenic purpura according to phases of disease course.

Abstract: Immune thrombocytopenic purpura (ITP) is an autoimmune thrombocytopenia with shortened platelet survival and relative bone marrow failure. The pathogenesis involves antibody production, cytokine release, T cell impairment, complement activation and clearance of platelets. We measured plasma levels of C3, C4, C1q and sC5b-9 in 80 ITP patients in acute phase, 50 ITP patients in complete (CR) or partial (PR) remission and 50 age- and sex-matched healthy volunteers. Statistical analyses showed that acute ITP patients had higher plasma levels of sC5b-9 and C1q than CR or PR patients (median = sC5b-9: 200 versus 98 mg/dl, P-value < 0·001) (median C1q = 2·11 versus 1·00 mg/dl, P-value < 0·001). CR and PR ITP patients had sC5b-9 and C1q plasma levels comparable to those observed in healthy volunteers. There was a significant correlation between sC5b-9 and C1q plasma levels (Spearman's rho correlation index on 130 ITP patients equal to 0·58, P-value < 0·001). We also found that sC5b-9 plasma level is inversely correlated with the number of platelets. Furthermore, we divided acute ITP patients into subjects with detectable (24 of 80, 30%) or undetectable (56 of 80, 70%) anti-platelet antibodies; patients with detectable anti-platelet antibodies have significantly higher plasma levels of C1q and sC5b-9. This research will potentially offer novel therapeutic strategies in light of new drugs affecting complement activation for monitoring therapy response.

Castelli|R|R|0000-0003-3976-7690
Lambertenghi Delilliers|G|G|
Gidaro|A|A|
Cicardi|M|M|
Bergamaschini|L|L|

ITP
thrombocytopenia
C1q
sC5b-9
Anti-platelet antibody
complement system
immunoglobulin


Thromboembolic events identified during diagnosis of germ cell tumors in 2 children.

Abstract: We describe 2 cases in which radiographic evidence of thromboembolic events was obtained during germ cell tumor diagnosis. There was no evidence of coagulation factor abnormalities or contributory procedures or drugs in either patient. We used anticoagulation therapy for thrombolysis in one patient, but in the other, the thromboembolism resolved spontaneously.

Oh|Hea-Lin|HL| Kang|Hae-Ryong|HR| Jeon|Seok-Cheol|SC| Lee|Young-Ho|YH|

Thromboembolism
Germ cell tumor
Chemotherapy


Bitter experiences of elderly parents of children with intellectual disabilities: A phenomenological study.

Abstract:
BACKGROUND
It is predicted that over the next 30 years, there will be a significant increase in the number of elderly parents who care for their children with intellectual disability. This paper is part of a larger qualitative study which investigated the unpleasant experiences of these parents.

MATERIALS AND METHODS
A phenomenological approach was adopted and data were collected through unstructured in-depth interviews with elderly parents of children with intellectual disability. The data were analyzed using Colaizzi's seven-step method.

RESULTS
"Bitterness" is one of the four emergent themes extracted in this study which has five theme clusters: inappropriate behavior toward the child in the society, the society's failure to support the child with intellectual disability, sorrows experienced by parents, the child's problems, and barriers in the care of the child with intellectual disability. One significant barrier in the last theme cluster is limitations due to aging.

CONCLUSIONS
The findings of this study suggest that the elderly parents of children with intellectual disability experience many sorrows and unpleasant feelings, but they mostly consider the social factors as the cause of problems and not the presence of the child. The results also indicate that older parents cannot look after the child as before in their old age; so, future well-designed studies are required for identification of the process of supporting them.

Hamedanchi|Arya|A|
Khankeh|Hamid Reza|HR|
Fadayevatan|Reza|R|
Teymouri|Robab|R|
Sahaf|Robab|R|

elderly parents
parents
children with intellectual disabilities
intellectual disability
phenomenology
Child
Iran
qualitative research


Salt acclimation process: a comparison between a sensitive and a tolerant Olea europaea cultivar.

Abstract: Saline soils are highly heterogeneous in time and space, and this is a critical factor influencing plant physiology and productivity. Temporal changes in soil salinity can alter plant responses to salinity, and pre-treating plants with low NaCl concentrations has been found to substantially increase salt tolerance in different species in a process called acclimation. However, it still remains unclear whether this process is common to all plants or is only expressed in certain genotypes. We addressed this question by assessing the physiological changes to 100 mM NaCl in two contrasting olive cultivars (the salt-sensitive Leccino and the salt-tolerant Frantoio), following a 1-month acclimation period with 5 or 25 mM NaCl. The acclimation improved salt tolerance in both cultivars, but activated substantially different physiological adjustments in the tolerant and the sensitive cultivars. In the tolerant Frantoio the acclimation with 5 mM NaCl was more effective in increasing plant salt tolerance, with a 47% increase in total plant dry mass compared with non-acclimated saline plants. This enhanced biomass accumulation was associated with a 50% increase in K+ retention ability in roots. On the other hand, in the sensitive Leccino, although the acclimation process did not improve performance in terms of plant growth, pre-treatment with 5 and 25 mM NaCl substantially decreased salt-induced leaf cell ultrastructural changes, with leaf cell relatively similar to those of control plants. Taken together these results suggest that in the tolerant cultivar the acclimation took place primarily in the root tissues, while in the sensitive they occurred mainly at the shoot level.

Pandolfi|Camilla|C| Bazihizina|Nadia|N| Giordano|Cristiana|C| Mancuso|Stefano|S| Azzarello|Elisa|E|

acclimation
Olea europaea
salinity
hardening
ion fluxes
potassium


Altered proliferative ability of neuronal progenitors in PlexinA1 mutant mice.

Abstract: Cortical interneurons are generated predominantly in the medial ganglionic eminence (MGE) and migrate through the ventral and dorsal telencephalon before taking their final positions within the developing cortical plate. Previously we demonstrated that interneurons from Robo1 knockout (Robo1(-/-)) mice contain reduced levels of neuropilin 1 (Nrp1) and PlexinA1 receptors, rendering them less responsive to the chemorepulsive actions of semaphorin ligands expressed in the striatum and affecting their course of migration (Hernandez-Miranda et al. [2011] J. Neurosci. 31:6174-6187). Earlier studies have highlighted the importance of Nrp1 and Nrp2 in interneuron migration, and here we assess the role of PlexinA1 in this process. We observed significantly fewer cells expressing the interneuron markers Gad67 and Lhx6 in the cortex of PlexinA1(-/-) mice compared with wild-type littermates at E14.5 and E18.5. Although the level of apoptosis was similar in the mutant and control forebrain, proliferation was significantly reduced in the former. Furthermore, progenitor cells in the MGE of PlexinA1(-/-) mice appeared to be poorly anchored to the ventricular surface and showed reduced adhesive properties, which may account for the observed reduction in proliferation. Together our data uncover a novel role for PlexinA1 in forebrain development.

Andrews|William D|WD|
Davidson|Kathryn|K|
Tamamaki|Nobuaki|N|
Ruhrberg|Christiana|C|
Parnavelas|John G|JG|

D000818:Animals
D017209:Apoptosis
D002448:Cell Adhesion
D002465:Cell Movement
D049109:Cell Proliferation
D002478:Cells, Cultured
D002540:Cerebral Cortex
D005968:Glutamate Decarboxylase
D049452:Green Fluorescent Proteins
D007150:Immunohistochemistry
D017403:In Situ Hybridization
D007395:Interneurons
D060850:LIM-Homeodomain Proteins
D008810:Mice, Inbred C57BL
D018345:Mice, Knockout
D009419:Nerve Tissue Proteins
D058953:Neural Stem Cells
D055495:Neurogenesis
D011956:Receptors, Cell Surface
D014157:Transcription Factors

interneurons
forebrain
proliferation
Plexin
neuronal migration


Clinical features and pregnancy outcome in antiphospholipid syndrome patients with history of severe pregnancy complications.

Abstract: Abstract Objective. To clarify the clinical significance of antiphospholipid antibody (aPL) profile in patients with obstetric antiphospholipid syndrome (APS). Methods. Clinical records of 13 pregnant patients (15 pregnancies) with obstetrical APS were reviewed over 10 years. Patients who met the Sapporo Criteria fully were studied, whereas those with only early pregnancy loss were excluded. In addition to classical aPL: lupus anticoagulant (LA), anticardiolipin antibody (aCL), and anti-β2-glycoprotein I (aβ2GPI); phosphatidylserine-dependent anti-prothrombin antibody (aPS/PT) and kininogen-dependent anti-phosphatidylethanolamine antibody (aPE) were also examined in each case. Results. Cases were divided into two groups according to patient response to standard treatment: good and poor outcome groups. All cases with poor outcome presented LA, with IgG aβ2GPI and IgG aPS/PT were also frequently observed. IgG aPE did not correlate with pregnancy outcome. Conclusion. aPL profile may predict pregnancy outcome in patients with this subset of obstetric APS.

Matsuki|Yuko|Y| Atsumi|Tatsuya|T| Yamaguchi|Koushi|K| Hisano|Michi|M| Arata|Naoko|N| Oku|Kenji|K| Watanabe|Noriyoshi|N| Sago|Haruhiko|H| Takasaki|Yoshinari|Y| Murashima|Atsuko|A|


Physicians, patients, and Facebook: Could you? Would you? Should you?

Abstract: This article investigates the opinions of physicians and patients regarding the use of Facebook to communicate with one another about health-related issues. We analyzed 290 comments posted on online discussion boards and found that most (51.7%) were opposed to physicians being Facebook "friends" with patients and many (42%) were opposed to physicians having any kind of Facebook presence. Some believed that health care organizations should have a social media policy and provide social media training. We conclude with suggestions for how health care administrators can provide assistance to physicians and effectively manage their social media presence.

Peluchette|Joy V|JV|
Karl|Katherine A|KA|
Coustasse|Alberto|A|

physicians
patients
Facebook
social media
privacy


Sex and weaponry: The distribution of toxin-storage glands on the bodies of male and female cane toads (Rhinella marina).

Abstract: The parotoid macroglands of bufonid anurans store (and can expel) large volumes of toxic secretions and have attracted detailed research. However, toxins also are stored in smaller glands that are distributed on the limbs and dorsal surface of the body. Female and male cane toads (Rhinella marina) differ in the location of toxin-storage glands and the extent of glandular structures. Female toads store a larger proportion of their toxins in the parotoids than males as well as (to a lesser extent) in smaller glands on the forelimbs. Males have smaller and more elongate parotoids than females, but glands cover more of the skin surface on their limbs (especially hindlimbs) and dorsal surface. The delay to toxin exudation in response to electrostimulation varied among glands in various parts of the body, and did so differently in males than in females. The spatial distribution of toxin glands differs between the sexes even in toads that have been raised under standardized conditions in captivity; hence, the sexual dimorphism is due to heritable factors rather than developmentally plastic responses to ecological (e.g., habitat, predation risk) differences between the sexes. The selective advantages of this sexual dimorphism remain unclear. A priori, we might expect to see toxin widely dispersed across any part of the body likely to be contacted by a predator; and a wide distribution also would be expected if the gland secretions have other (e.g., male-male rivalry) functions. Why, then, is toxin concentrated in the parotoids, especially in female toads? That concentration may enhance the effectiveness of frontal displays to deter predation and also may facilitate the transfer of stored toxins to eggs.

Chen|Wei|W|
Hudson|Cameron M|CM|
DeVore|Jayna L|JL|
Shine|Richard|R|0000-0001-7529-5657

sexual dimorphism
Bufo marinus
antipredator
bufadienolide
bufotoxin
chemical defense


Impact of Oral Health Education on the Knowledge, Behaviors, Attitudes, and Self-Efficacy of Caregivers for Individuals with Intellectual and Developmental Disabilities.

Abstract: Purpose: Individuals with intellectual and developmental disabilities (IDD) have a higher risk of oral disease and require assistance in performing oral self-care. The purpose of this study was to measure the impact of an oral health education program in improving caregivers' oral health knowledge, attitudes, behavior, and self-efficacy in providing oral health care to clients with IDD, residing in intermediate care facilities.Methods: A non-probability sample of new hire caregivers (n=47) for clients with IDD residing in an intermediate care facility was used for this quasi-experimental study. A one-group repeated measures design was used to explore the effectiveness of an oral health education program. All variables were examined using summary statistics and evaluated for normality and statistical assumptions.Results: Forty-seven participants attended the oral health education program intervention and completed the pre- and post-intervention questionnaire. Seventy percent (n=33) completed the four-week post-questionnaire. A statistically significant (p=0.004) improvement in knowledge between the baseline questionnaire and four-week questionnaire was identified. Findings demonstrated slight increases in knowledge for caregivers with <1 year experience, and in those with previous medical training. No significant differences were found in behaviors or attitudes from baseline to the four-week follow up, however, there was a trend toward positive behavior changes.Conclusion: Increased knowledge alone is not adequate to bring about and maintain positive oral health behavior change. Longer-term caregiver interventions, in addition to on-site support for oral care, are warranted to evaluate outcomes for individuals with IDD with the goal of reducing the burden of oral disease.

Selbera|Lindsay M|LM|
Boyd|Linda D|LD|
Vineyard|Jared|J|
Smallidge|Dianne L|DL|

oral health
oral health education
caregivers
developmental disabilities
intermediate care facility
oral care
intellectual disabilities


A novel method for determining the adequate dose of a chelating agent for phytoremediation of radionulides contaminated soils by M. cordata.

Abstract: A chelating agent in an adequate dose used to enhance phytoremediation of radionuclide-contaminated soil should not inhibit the growth of the plant. If this constraint condition is satisfied, the total bioaccumulation amount (TBA) of radionuclide by the plant can be maximized. This is a constrained optimization problem to determine the adequate dose of the chelating agent for phytoremediation of radionuclide-contaminated soil. In this research, an adequate dose of a chelating agent for phytoremediation of radionuclide-contaminated soil was determined by a novel approach using pot experiments. The proposed approach was applied to specify the adequate doses of citric acid (CA) and S,S-ethylenediamine disuccinic acid (EDDS) for phytoremediation of uranium contaminated soil by M. Cordata. By using this method, the adequate doses of CA and EDDS for phytoremediation of 238U, 232Th and 226Ra contaminated soils by M. cordata were measures as 10.0 and 5.0 mmol kg-1, respectively. The results showed that the approach could be used to establish the adequate dose of a chelating agent for phytoremediation of radionuclide or other toxic heavy metal contaminated soil by a plant.

Hu|Nan|N| Chen|Siyu|S| Lang|Tao|T| Zhang|Hui|H| Chen|Wei|W| Li|Guangyue|G| Ding|Dexing|D|

D001673:Biodegradation, Environmental
D002614:Chelating Agents
D011834:Radiation Monitoring
D012987:Soil
D012990:Soil Pollutants, Radioactive

Phytoremediation
Radionuclides
Constrained optimization
Chelating agent dose


Separation of haemocyte subpopulations in shrimp Fenneropenaeus chinensis by immunomagnetic bead using monoclonal antibody against granulocytes.

Abstract: In our previous work, two monoclonal antibodies (Mabs) against granulocytes of shrimp (Fenneropenaeus chinensis) had been produced, in this paper, haemocyte subpopulations were analyzed by flow cytometry (FCM) using the Mabs. Then immunomagnetic bead (IMB) method was applied for separation hyalinocytes and granulocytes using the Mabs. The separated hyalinocytes and granulocytes were analyzed by FCM, indirect immunofluorescence assay, Giemsa staining and transmission electron microscopy, respectively. The results showed the proportion of hyalinocytes in haemolymph of F. chinensis was 15.14 ± 1.22%, and that of granulocytes was 75.43 ± 2.31%. After two times separation by IMB, the purity rate of hyalinocytes and granulocytes was 96.27 ± 1.06% and 98.13 ± 0.86%, respectively. The hyalinocytes possessed 0.60-0.85 in nucleus/cytoplasm (N/C) ratio and had few granule in cytoplasm, whereas the separated granulocytes with N/C ratio of 0.12-0.36 and high electronic density of double membrane granules. The results reported the separation of haemocyte subpopulations using Mabs in shrimp for the first time, and the hyalinocytes and granulocytes isolated by IMB could be used for their differential protein analysis.

Xing|Jing|J| Chang|Yanhong|Y| Tang|Xiaoqian|X| Sheng|Xiuzhen|X| Zhan|Wenbin|W|

Fenneropenaeus chinensis
Immunomagnetic bead
Monoclonal antibody
Granulocytes
Hyalinocytes


Adipose-derived stromal vascular fraction aids epithelialisation and angiogenesis in an animal model.

Abstract:
OBJECTIVE
Limited data exist regarding the correlation between adipose-derived stromal vascular fraction (SVF) and wound healing. The aim of this study was to investigate the direct effect of intradermally injected SVF on full-thickness cutaneous wounds in a murine model.

METHOD
Wistar rats were divided into three groups (A, B and C) according to their day of euthanasia (day 7, 16 and 21). Inguinal fat pad was excised and SVF enzymatically extracted. Full-thickness cutaneous wounds were created on each side of the dorsum; SVF injected intradermally at one side while the contralateral wound served as control receiving normal saline. Postoperatively, evaluation of wound healing was performed by planimetry (percentages of wound contraction, epithelialisation and total wound healing) on days 0, 3, 5, 7, 10, 13, 16 and 21, and histology and immunochemistry (cellular infiltration score, collagen production score, neoangiogenesis and epithelial thickness) on days 7, 16 and 21.

RESULTS
Despite the high rate of wound contraction, it was significantly lower in the SVF-treated wounds on day 21 (p=0.037). On days 13, 16 and 21, the percentages of epithelialisation were higher in the SVF-treated wounds compared with control wounds (p=0.026, p=0.048 and p=0.05, respectively). Histologically, the number of new vessels was significantly higher in the SVF-treated wounds compared with controls on days seven (p=0.028) and 16 (p=0.027). This was also confirmed by immunohistochemistry. No significant differences were found between treated and control wounds regarding cellular infiltration score, collagen production score and epithelial thickness.

CONCLUSION
Data indicate that intradermally injected SVF increases angiogenesis and enhances epithelialisation in full-thickness cutaneous wounds in rats.

Karagergou|Eleni|E| Dionyssopoulos|Alexandros|A| Karayannopoulou|Maria|M| Psalla|Dimitra|D| Theodoridis|Alexandros|A| Demiri|Efterpi|E| Koliakos|Georgios|G|


Nanoparticles' properties modify cell type-dependent distribution in immune cells.

Abstract: Polymeric nanoparticles can passively target inflamed tissues. How their physicochemical properties affect their distribution pattern among the infiltrating immune cells is unknown. Polyvinyl acetate nanoparticles with different particle size (100 and 300 nm) and surface charge (cationic, non-ionic, and anionic) were prepared and incubated with either LPS-activated or unactivated murine splenocytes. Nanoparticle association with macrophages, dendritic cells, neutrophils, B and T cells was investigated using flow cytometry. Cells associated with nanoparticles as follows: cationic>anionic>non-ionic and 300 nm > 100 nm. 40% of ionic nanoparticles were distributed among unactivated macrophages, reduced to 25% for activated macrophages. 60% of 100 nm and 40% of 300 nm non-ionic nanoparticles were distributed among unactivated and LPS-activated macrophages. This study highlights that particles' physicochemical properties impact the number of nanoparticles associating with immune cells more than their distribution pattern, which is principally determined by the cell activation state. This suggests a disease-dependent distribution pattern for therapeutic nanoparticles.

Youshia|John|J|
Ali|Mohamed Ehab|ME|
Stein|Valentin|V|
Lamprecht|Alf|A|

Distribution
Immune cells
Polymeric nanoparticles
Particle size
Surface charge
Flow cytometry


Relationship between high-sensitivity C reactive protein and the risk of gallstone disease: results from the Kailuan cohort study.

Abstract:
OBJECTIVES
Gallstone disease (GSD) can be caused by various health and clinical factors such as obesity, dyslipidaemia and an unhealthy diet, all of which are associated with higher high-sensitivity C reactive protein (hs-CRP) concentrations. Whether hs-CRP represents an independent risk factor for GSD is still unclear. We prospectively investigated hs-CRP in relation to the occurrence of GSD based on the Kailuan study.

STUDY DESIGN
Prospective cohort study.

SETTING
The Kailuan cohort study was conducted in Tangshan City in northern China.

PARTICIPANTS
95 319 participants who were free from GSD were recruited in this study. Epidemiological data, anthropometric parameters and biochemical data of participants were collected.

PRIMARY AND SECONDARY OUTCOME MEASURES
Cox proportional hazards regression models were used to evaluate the association between hs-CRP concentrations and the risk of GSD after adjustments for potential confounders.

RESULTS
During the mean 7.58 years of follow-up among 95 319 participants, 4205 participants were identified as newly diagnosed with GSD or having undergone cholecystectomy for cholelithiasis. Compared with the hs-CRP<1 mg/L group, elevated hs-CRP concentrations were significantly associated with higher risk of GSD with the corresponding HR of 1.11 (95% CI 1.03 to 1.19), 1.12 (95% CI 1.04 to 1.22) in the 1≤hs-CRP≤3 mg/L and hs-CRP>3 mg/L group, respectively. The multivariate model which included hs-CRP not only had a better line of fitness but also had better predictive values to help identify new cases of GSD during follow-up.

CONCLUSION
Elevated hs-CRP concentration is an independent risk factor for new-onset GSD among the Chinese population.

TRIAL REGISTRATION NUMBER
ChiCTR-TNC-11001489.

Liu|Tong|T|
Siyin|Sarah Tan|ST|
Yao|Nan|N|
Duan|Ning|N|
Xu|Guoshuai|G|
Li|Wenqiang|W|
Qu|Jun|J|0000-0002-9738-2038
Liu|Siqing|S|

gastroenterology
motility disorders
public health


Vascularized Composite Allograft Donation and Transplantation: A Survey of Public Attitudes in the United States.

Abstract: Vascularized composite allograft (VCA) transplantation has emerged as a groundbreaking surgical intervention to return identity and function following traumatic injury, congenital deformity, or disfigurement. While public attitudes toward traditional organ/tissue donation are favorable, little is known about attitudes toward VCA donation and transplantation. A survey was conducted of 1485 U.S. residents in August 2016 to assess VCA donation attitudes. Participants also completed the Revised Health Care System Distrust Scale. Most respondents were willing to donate hands/forearms (67.4%) and legs (66.8%), and almost half (48.0%) were willing to donate the face. Three-quarters (74.4%) of women were willing to donate the uterus; 54.4% of men were willing to donate the penis. VCA donation willingness was more likely among whites and Hispanics (p < 0.001), registered organ/tissue donors (p < 0.001), and those with less health care system distrust (p < 0.001) and media exposure to VCA transplantation (p = 0.003). Many who opposed VCA donation expressed concerns about psychological discomfort, mutilation, identity loss, and the reaction of others to seeing familiar body parts on a stranger. Attitudes toward VCA donation are favorable overall, despite limited exposure to VCA messaging and confusion about how VCA donation occurs. These findings may help guide the development and implementation of VCA public education campaigns.

Rodrigue|J R|JR|
Tomich|D|D|
Fleishman|A|A|
Glazier|A K|AK|

D001294:Attitude to Health
D064595:Composite Tissue Allografts
D005260:Female
D006801:Humans
D008297:Male
D016377:Organ Transplantation
D011639:Public Opinion
D011795:Surveys and Questionnaires
D009927:Tissue and Organ Procurement
D014184:Transplantation, Homologous
D014481:United States

vascularized composite and reconstructive transplantation


Remote rehabilitation for patients with COVID-19.

Abstract:
OBJECTIVE
To describe the effectiveness and risk management of remote rehabilitation for coronavirus disease (COVID-19) patients.

DESIGN
Single-centre, retrospective, observational study.

PATIENTS
COVID-19 patients undergoing rehabilitation (24 April to 24 May 2020).

METHODS
All COVID-19 inpatients undergoing rehabilitation in the general ward were assessed. Data were collected on age, sex, physical ability, rehabilitation modality (remote/direct), need for intubation or extracorporeal membrane oxygenation, degree of pneumonia, oxygen therapy from the start of rehabilitation, D-dimer and C-reactive protein levels, and rehabilitation-related complications. Activities of daily living were measured using the Barthel Index.

RESULTS
Out of a total of 43 patients, 14 were initially provided with remote rehabilitation and 29 with direct rehabilitation. Four patients were switched from direct to remote rehabilitation during the study, thus at the end of the study there were 18 in the remote rehabilitation group and 25 in the direct rehabilitation group. Patients in remote rehabilitation were significantly younger than those in direct rehabilitation. Of 12 patients who required intubation, 3 were given remote rehabilitation. One extracorporeal membrane oxygenation survivor underwent direct rehabilitation. All patients on remote rehabilitation were discharged home or to a hotel. Twelve out of 29 patients were transferred to a rehabilitation hospital due to delayed recovery of activities of daily living. No serious adverse events occurred.

CONCLUSION
Effective and safe remote rehabilitation was performed in 41.9% of COVID-19 patients in this study, which resulted in improved rehabilitation in COVID-19 zones.

Sakai|Tomoko|T| Hoshino|Chisato|C| Yamaguchi|Reiko|R| Hirao|Masanobu|M| Nakahara|Rui|R| Okawa|Atsushi|A|

rehabilitation
risk management
coronavirus
early ambulation
infection
pulmonary embolism


Application of CRISPR-Cas9 for Long Noncoding RNA Genes in Cancer Research.

Abstract: Long noncoding RNAs (LncRNA), a class of transcripts with lengths >200 nt, play a master role in the regulation of cancer pathogenesis. Recently, the CRISPR-Cas9 system has been explored as a revolutionary genome editing tool for molecular biology. Growing evidence shows that LncRNAs can be targeted by the CRISPR-Cas9 system used for evaluating its function. Thus, the CRISPR-Cas9 systems provide a novel gene-editing strategy for the modification of LncRNA expression. This review summarizes current knowledge of the functions and underlying mechanisms of LncRNA by CRISPR-Cas9. Emerging strategies for non-viral/viral delivery of CRISPR-Cas9 in a clinical context are also discussed.

D015972:Gene Expression Regulation, Neoplastic


Comparison of methods for estimating genetic correlation between complex traits using GWAS summary statistics.

Abstract: Genetic correlation is the correlation of phenotypic effects by genetic variants across the genome on two phenotypes. It is an informative metric to quantify the overall genetic similarity between complex traits, which provides insights into their polygenic genetic architecture. Several methods have been proposed to estimate genetic correlation based on data collected from genome-wide association studies (GWAS). Due to the easy access of GWAS summary statistics and computational efficiency, methods only requiring GWAS summary statistics as input have become more popular than methods utilizing individual-level genotype data. Here, we present a benchmark study for different summary-statistics-based genetic correlation estimation methods through simulation and real data applications. We focus on two major technical challenges in estimating genetic correlation: marker dependency caused by linkage disequilibrium (LD) and sample overlap between different studies. To assess the performance of different methods in the presence of these two challenges, we first conducted comprehensive simulations with diverse LD patterns and sample overlaps. Then we applied these methods to real GWAS summary statistics for a wide spectrum of complex traits. Based on these experiments, we conclude that methods relying on accurate LD estimation are less robust in real data applications due to the imprecision of LD obtained from reference panels. Our findings offer guidance on how to choose appropriate methods for genetic correlation estimation in post-GWAS analysis.

D019985:Benchmarking
D015331:Cohort Studies
D003198:Computer Simulation
D000068598:Data Accuracy
D005787:Gene Frequency
D015894:Genome, Human
D055106:Genome-Wide Association Study
D005838:Genotype
D006801:Humans
D015810:Linkage Disequilibrium
D020412:Multifactorial Inheritance
D010641:Phenotype
D020641:Polymorphism, Single Nucleotide

genetic correlation
complex traits
GWAS summary statistics
benchmarking


Therapeutic surgery without a definitive diagnosis can be an option in selected patients with suspected lung cancer.

Abstract:
OBJECTIVES
With the recent improvements in the diagnostic accuracy of radiographic modalities, it might be an option to perform therapeutic surgery without a definitive diagnosis for selected patients with suspected lung cancer based on the findings of diagnostic imaging.

METHODS
Between April 2008 and December 2012, all nodules without a definitive diagnosis were classified into five categories according to the probability of lung cancer based on the diagnostic imaging: Category 1 (Benign), Category 2 (Probably benign), Category 3 (Intermediate), Category 4 (Suspected malignancy) and Category 5 (Highly suggestive of malignancy). In this study, the 232 surgical candidates for suspected clinical stage I lung cancer without a preoperative definitive diagnosis were considered to be Category 3 (n = 29), Category 4 (n = 46) and Category 5 (n = 157). Eighty-two patients (72% of Category 3, 46% of Category 4 and 25% of Category 5) had an intraoperative diagnosis during surgery, whereas the remaining 150 patients did not. The final pathological diagnosis and surgical outcomes were analysed.

RESULTS
The final pathological diagnosis of the 232 suspicious nodules revealed 214 lung cancers (52% of Category 3, 93% of Category 4 and 99% of Category 5). Wedge resection was performed for all seven benign tumours. In the multiple regression analysis, intraoperative diagnosis was a significant factor for the length of the operation. In the multivariate logistic regression analysis, the length of the operation was a significant factor predicting both the postoperative morbidity and a prolonged hospital stay.

CONCLUSIONS
Based on a careful clinical decision made using the current diagnostic imaging strategies, patients with a high probability of lung cancer are good candidates for therapeutic surgery, even without a preoperative or intraoperative definitive diagnosis.

Ozeki|Naoki|N| Iwano|Shingo|S| Taniguchi|Tetsuo|T| Kawaguchi|Koji|K| Fukui|Takayuki|T| Ishiguro|Futoshi|F| Fukumoto|Koichi|K| Nakamura|Shota|S| Hirakawa|Akihiro|A| Yokoi|Kohei|K|

Surgery
Diagnosis
Lung cancer
Frozen section


Attention-deficit/hyperactivity disorder symptoms and suicide ideation and attempts: Findings from the Adult Psychiatric Morbidity Survey 2007.

Abstract:
BACKGROUND
Adults with attention-deficit/hyperactivity disorder (ADHD) may have an increased risk of engaging in suicidal behavior. This study examined this association in the general adult population where there has been little research.

METHODS
Data came from the Adult Psychiatric Morbidity Survey 2007. This was a representative sample of the English adult household population aged ≥16 years (N=7403). The Adult ADHD Self-Report Scale (ASRS) was used to obtain information on ADHD symptoms. The Clinical Interview Schedule Revised (CIS-R) was used to assess six forms of common mental disorder (CMD). Information was also obtained on the lifetime and past 12-month occurrence of suicide ideation and attempts. Logistic regression analysis was used to examine these associations.

RESULTS
After adjusting for comorbid disorders, adults with more ADHD symptoms had significantly higher odds for suicidal behavior. When a single cut-off point was used to classify ADHD (ASRS score ≥14), odds ratios ranged from 1.62 (lifetime suicide attempt) to 2.43 (past 12-month suicide ideation). When ADHD symptoms were categorized by strata (I: a score of 0-9; II: 10-13; III: 14-17; IV: 18-24), compared to adults in stratum I, those in stratum IV had odds ratios ranging from 2.16 (lifetime suicide ideation) to 3.68 (past 12-month suicide attempt).

LIMITATIONS
ADHD and suicide data came from self-reports which may have been affected by socially desirable responding.

CONCLUSIONS
ADHD symptoms were linked to suicidal behavior after controlling for comorbid conditions. Health care professionals should be alerted to the increased suicide risk among adults with ADHD symptoms.

Stickley|Andrew|A| Koyanagi|Ai|A| Ruchkin|Vladislav|V| Kamio|Yoko|Y|

D001289:Attention Deficit Disorder with Hyperactivity

Suicidal ideation
ADHD
Common mental disorders
Suicide attempt
APMS 2007


Manipulation of a master manipulator with a combined-grip-handle of pinch and power grips.

Abstract: Conventional robotic surgery employs pinch and power grips for manipulating a master manipulator. As such, the manipulating methods exhibit limitations that are strongly related to the advantages and disadvantages of the gripping type. The context of this paper is focused on the introduction of a combined grip to compensate for such restraints. In particular, this paper proposed the combined-grip-handle scheme on a master manipulator, which employs both the pinch and power grips. A pointing experiment applying the master-slave scheme was conducted with the master manipulator under several manipulating conditions of the combined grip and the conventional gripping types. Results of using the combined grip demonstrated that the positioning operation performed with fewer failures and required shorter time and trajectory. Compared with the conventional gripping types, the proposed combined grip showed better performance on the positioning operation and provided a possibility to perform precise work at lower scale factors.

robotic surgery
manipulating method
gripping type
handle
master slave system


Tuning the Solubility of Self-Assembled Fluorescent Aromatic Cages Using Functionalized Amino Acid Building Blocks.

Abstract: We previously reported novel fluorescent aromatic cages that are self-produced using a set of orthogonal dynamic covalent reactions, operating simultaneously in one-pot, to assemble up to 10 components through 12 reactions into a single cage-type structure. We now introduce N-functionalized amino acids as new building blocks that enable tuning the solubility and analysis of the resulting cages. A convenient divergent synthetic approach was developed to tether different side chains on the N-terminal of a cysteine-derived building block. Our studies show that this chemical functionalization does not prevent the subsequent self-assembly and effective formation of desired cages. While the originally described cages required 94% DMSO, the new ones bearing hydrophobic side chains were found soluble in organic solvents (up to 75% CHCl3), and those grafted with hydrophilic side chains were soluble in water (up to 75% H2O). Fluorescence studies confirmed that despite cage functionalization the aggregation-induced emission properties of those architectures are retained. Thus, this work significantly expands the range of solvents in which these self-assembled cage compounds can be generated, which in turn should enable new applications, possibly as fluorescent sensors.

Konopka|Marcin|M|
Cecot|Piotr|P|
Ulrich|Sébastien|S|
Stefankiewicz|Artur R|AR|

self-assembly
fluorescence
disulfides
dynamic covalent chemistry
molecular cages


The Arabidopsis polyamine transporter LHR1/PUT3 modulates heat responsive gene expression by enhancing mRNA stability.

Abstract: Polyamines involve in gene regulation by interacting with and modulating the functions of various anionic macromolecules such as DNA, RNA and proteins. In this study, we identified an important function of the polyamine transporter LHR1 (LOWER EXPRESSION OF HEAT RESPONSIVE GENE1) in heat-inducible gene expression in Arabidopsis thaliana. The lhr1 mutant was isolated through a forward genetic screening for altered expression of the luciferase reporter gene driven by the promoter from the heat-inducible gene AtHSP18.2. The lhr1 mutant showed reduced induction of the luciferase gene in response to heat stress and was more sensitive to high temperature than the wild type. Map-based cloning identified that the LHR1 gene encodes the polyamine transporter PUT3 (POLYAMINE UPTAKE TRANSPORTER 3) localized in the plasma membrane. The LHR1/PUT3 is required for the uptake of extracellular polyamines and plays an important role in stabilizing the mRNAs of several crucial heat stress responsive genes under high temperature. Genome-wide gene expression analysis using RNA-seq identified an array of differentially expressed genes, among which the transcript levels of some of the heat shock protein genes significantly reduced in response to prolonged heat stress in the lhr1 mutant. Our findings revealed an important heat stress response and tolerance mechanism involving polyamine influx which modulates mRNA stability of heat-inducible genes under heat stress conditions.

Shen|Yun|Y| Ruan|Qingxia|Q| Chai|Haoxi|H| Yuan|Yongze|Y| Yang|Wannian|W| Chen|Junping|J| Xin|Zhanguo|Z| Shi|Huazhong|H|

polyamine transport
polyamines
PUT3
mRNA stability
gene regulation
Arabidopsis thaliana
heat stress


Preliminary report of the relationship between experience of death of a relative, illness perception, and psychological outcome among BRCA carriers.

Abstract: With recent advances in mapping the genetic mutations involved in breast cancer and the availability of genetic testing, it has become necessary to explore the psychological consequences of women who have tested positive for the gene mutations involved in breast cancer (BReast CAncer gene one and two, BRCA1/2). Findings regarding psychological consequences of positive results in genetic testing for breast cancer are ambiguous and insufficient. The aim of the current study was to explore the relationship between experience of the death of a relative due to breast cancer, perception of the illness, distress, and well-being among BRCA1/2 mutation women carriers. Forty asymptomatic carriers who attended BRCA1/2 clinics in Israel completed self-administered questionnaires assessing socio-demographic variables, illness perception, and well-being. It was found that experiencing the death of a relative as a result of breast cancer was significantly correlated with illness perception. Carriers who experienced the death of a relative perceived breast cancer as having a stronger identity (i.e. as having severe symptoms), dire consequences, and as being uncontrollable in comparison to carriers who had not experienced the death of a relative. Nevertheless, psychological distress and well-being were not found to be significantly correlated to either an experience of death of a relative as a result of breast cancer or to illness perception. Implications and limitations are discussed in light of these findings. Among these is the need to consider the illness perception of healthy BRCA carriers women.

Samama|Dikla|D| Hasson-Ohayon|Ilanit|I| Perry|Shlomit|S| Morag|Ofir|O| Goldzweig|Gil|G|

illness perception
genetics
psychological distress
psycho-oncology


Prevalence of autoimmune diseases and other associated conditions in children and young adults with juvenile idiopathic arthritis.

Abstract:
OBJECTIVE
Many autoimmune diseases share common pathogenic mechanisms; however, there are limited studies quantifying the coexistence of autoimmune diseases and associated conditions in patients with juvenile idiopathic arthritis (JIA). This large US-based study estimated and compared the prevalence of multiple coexisting autoimmune diseases in patients with JIA with a general paediatric (GP) patient population.

METHODS
This retrospective cohort study was conducted using registry data from the Cincinnati Children's Hospital Medical Center (January 2010-October 2018). The prevalence of multiple autoimmune diseases was estimated in patients (age <21 years) with JIA and a control group from the GP patient population. Crude prevalences of 26 prespecified autoimmune diseases and associated conditions were compared using Bayesian Poisson regression modelling for each year up to the end of the study period.

RESULTS
Overall, 2026 patients were included in the JIA cohort and 41 572 in the GP cohort. Of 26 autoimmune diseases and associated conditions evaluated, 14 (53.8%) had a significantly higher prevalence in the JIA cohort compared with the GP cohort. In total, seven (26.9%) autoimmune diseases or associated conditions had a >20-fold increased prevalence in the JIA cohort compared with the GP cohort.

CONCLUSION
In this study, patients with JIA had a greater prevalence of a large number of coexisting autoimmune diseases and associated conditions compared with the GP population. Physicians should consider coexisting autoimmune diseases in the treatment and management of patients with JIA.

prevalance
autoimmune diseases
arthritis juvenile


Enly: Improving Draft Genomes through Reads Recycling.

Abstract: The reconstruction of the complete genome sequence of an organism is an important point for comparative, functional and evolutionary genomics. Nevertheless, overcoming the problems encountered while completing the sequence of an entire genome can still be demanding in terms of time and resources. We have developed Enly, a simple tool based on the iterative mapping of sequence reads at contig edges, capable to extend the genomic contigs deriving from high-throughput sequencing, especially those deriving by Newbler-like assemblies. Testing it on a set of de novo draft genomes led to the closure of up to 20% of the gaps originally present. Enly is cross-platform and most of the steps of its pipeline are parallelizable, making easy and fast to improve a draft genome resulting from a de novo assembly.

Fondi|Marco|M|
Orlandini|Valerio|V|
Corti|Giorgio|G|
Severgnini|Marco|M|
Galardini|Marco|M|
Pietrelli|Alessandro|A|
Fuligni|Fabio|F|
Iacono|Michele|M|
Rizzi|Ermanno|E|
De Bellis|Gianluca|G|
Fani|Renato|R|

454.
Contig extension
Genome assembly
Newbler
Next Generation Sequencing


Abstract: Nephrin is a core component of podocyte (glomerular epithelial cell) slit diaphragm and is required for kidney ultrafiltration. Down-regulation or mislocalization of nephrin has been observed in diabetic kidney disease (DKD), characterized by albuminuria. Here, we investigate the role of protein kinase C and casein kinase 2 substrate in neurons 2 (PACSIN2), a regulator of endocytosis and recycling, in the trafficking of nephrin and development of DKD. We observe that PACSIN2 is up-regulated and nephrin mislocalized in podocytes of obese Zucker diabetic fatty (ZDF) rats that have altered renal function. In cultured podocytes, PACSIN2 and nephrin colocalize and interact. We show that nephrin is endocytosed in PACSIN2-positive membrane regions and that PACSIN2 overexpression increases both nephrin endocytosis and recycling. We identify rabenosyn-5, which is involved in early endosome maturation and endosomal sorting, as a novel interaction partner of PACSIN2. Interestingly, rabenosyn-5 expression is increased in podocytes in obese ZDF rats, and, in vitro, its overexpression enhances the association of PACSIN2 and nephrin. We also show that palmitate, which is elevated in diabetes, enhances this association. Collectively, PACSIN2 is up-regulated and nephrin is abnormally localized in podocytes of diabetic ZDF rats. In vitro, PACSIN2 enhances nephrin turnover apparently via a mechanism involving rabenosyn-5. The data suggest that elevated PACSIN2 expression accelerates nephrin trafficking and associates with albuminuria.-Dumont, V., Tolvanen, T. A., Kuusela, S., Wang, H., Nyman, T. A., Lindfors, S., Tienari, J., Nisen, H., Suetsugu, S., Plomann, M., Kawachi, H., Lehtonen, S. PACSIN2 accelerates nephrin trafficking and is up-regulated in diabetic kidney disease.

Dumont|Vincent|V|
Tolvanen|Tuomas A|TA|
Kuusela|Sara|S|
Wang|Hong|H|
Nyman|Tuula A|TA|
Lindfors|Sonja|S|
Tienari|Jukka|J|
Nisen|Harry|H|
Suetsugu|Shiro|S|
Plomann|Markus|M|
Kawachi|Hiroshi|H|
Lehtonen|Sanna|S|

D048868:Adaptor Proteins, Signal Transducing

podocyte endocytosis recycling rabenosyn-5 palmitate


Tibiotalocalcaneal Arthrodesis Using a Novel Retrograde Intramedullary Nail.

Abstract: Background. Tibiotalocalcaneal (TTC) arthrodesis is a common treatment option for complex hindfoot pathology. Overall union rates range from 50% to 86% but can be even lower in certain populations. A novel retrograde intramedullary nail has recently been developed. The purpose of this study was to report fusion rates, time to weight-bearing, and complications with the use of the A3 Fusion Nail. Methods. All patients 18 years or older who underwent TTC arthrodesis with an A3 Fusion Nail at a single institution from 2010 to 2015 with a minimum 3-month follow-up were included in this study. Rates of successful fusion, time to union, time to weight-bearing, and complications were evaluated. A total of 20 patients with an average age of 58.1 years and an average follow-up of 12.5 months met inclusion criteria. Results. Successful TTC arthrodesis was achieved in 14 of 20 patients (70%) overall. Average time to union was 8.1 months, and average time to weight-bearing was 6.8 weeks. Of 20 patients, 17 (85%) required femoral head allograft for bulk bone defects, and the union rate in this subset of patients was 76.5%. The rates of revision surgery (10%) and complications were low. Conclusion. The A3 Fusion Nail demonstrated a favorable safety profile and achieved TTC arthrodesis at a rate consistent with historical data despite being used in a patient population at high risk for nonunion. In patients with bulk bone defects at high risk for nonunion, the A3 Fusion Nail demonstrated superior rates of fusion (76.5%) to those reported in the literature (50%).Level of Evidence: Level III: Retrospective cohort study.

tibiotalocalcaneal arthrodesis
A3 Fusion Nail
nonunion
hindfoot deformity


Abstract:
BACKGROUND
Although phalloplasty with a free radial forearm (RF) flap is the gold standard for sex reassignment surgery in female-to-male transsexuals, it can result in unsightly scars, lymphedema, and numbness of the hand.

AIM
To introduce the concept of flap combination phalloplasty and its clinical application.

METHODS
This is a retrospective chart review study of patients undergoing phalloplasty using various multiple flaps. Demographic data, surgical data, and outcomes were recorded.

OUTCOMES
Of the 15 cases, 5 were urethral fistulas; 4 were venous thrombosis; 2 were urethral calculus; and 1 was a partial flap loss.

RESULTS
15 patients were included (age range 25-43 years, median 34 years). An RF flap and a deep inferior epigastric artery perforator flap combination were most frequently used. The median operative time for flap combination phalloplasty was 10.5 hours (range 6.5-12.5 hours). There was no total flap necrosis, but there was 1 case of partial flap loss. There were urethral fistulas in 5, venous thrombosis in 4, and urethral calculus in 2 cases.

CLINICAL IMPLICATIONS
Flap combination phalloplasty will become the third option when both the RF flap and the anterolateral thigh pedicle flap are not useful.

STRENGTH & LIMITATIONS
Flap combination phalloplasty is a complex operative procedure with a prolonged operative time, but it can provide more flap selection and reduce the morbidity at each donor site. Choosing from many different options can be beneficial to patients.

CONCLUSION
Flap combination phalloplasty has a similar complication rate to other procedures and has advantages in terms of flexibility and less donor site morbidity; it may thus be an option when either the RF flap or the anterolateral thigh pedicle flap cannot be used. Namba Y, Watanabe T, Kimata Y. Flap Combination Phalloplasty in Female-to-Male Transsexuals. J Sex Med 2019;16:934-941.

Flap Combination Phalloplasty
Female-to-Male Transsexual
Sex Reassignment Surgery
Single Flap Phalloplasty


Retrospective analysis of in vivo recovery and clearance during continuous infusion of recombinant factor VIII products: a single-institution study.

Abstract:
BACKGROUND
Continuous infusion (CI) of recombinant FVIII (rFVIII) concentrates has been reported as an effective and safe method to achieve haemostasis during major surgeries or severe bleeding events. For more effective and safer CI, better understanding of in vivo recovery (IVR) and clearance (CL) issues is imperative.

OBJECTIVE
We investigated the following factors affecting IVR and CL using univariate and multivariate regression analyses during 47 CIs in 34 patients: rFVIII concentrate type, haemophilia severity, blood type, the presence of hepatitis C virus (HCV) or human immunodeficiency virus (HIV), age and body mass index (BMI).

RESULTS
The mean IVR was 1.64 ± 0.49 IU dL-1 per IU kg-1 , and the mean CL during CI was 3.56 ± 1.57 mL h-1 kg-1 . The univariate and multivariate regression analyses showed that the CL of octocog alfa was significantly lower than that of rurioctocog alfa (P = 0.043 and 0.0034, respectively). There was a significant difference in BMI in the univariate and multivariate regression analyses (P = 0.0403 and 0.0376, respectively).

CONCLUSIONS
This study indicated that CL during CI was potentially affected by the type of rFVIII concentrate used and BMI.

Suzuki|N|N| Hirakawa|A|A| Kishimoto|M|M| Kanematsu|T|T| Ogawa|M|M| Kiyoi|H|H| Matsushita|T|T|

D000328:Adult
D000368:Aged
D000369:Aged, 80 and over
D005169:Factor VIII
D006801:Humans
D007260:Infusion Pumps
D008875:Middle Aged
D011994:Recombinant Proteins
D012189:Retrospective Studies
D055815:Young Adult

in vivo recovery
clearance
factor VIII
haemophilia A
pharmacokinetics


FMRI-based prediction of naltrexone response in alcohol use disorder: a replication study.

Abstract: Pharmacological treatment in alcohol use disorder suffers from modest effect sizes. Efforts have been undertaken to identify patient characteristics that help to select individuals that benefit from pharmacological treatment. Previous studies indicated that neural alcohol cue-reactivity (CR) might provide a marker that identifies patients, which benefit from naltrexone treatment.We investigated the reproducibility of the association between ventral striatum (VS) activation and naltrexone (NTX) treatment response by analyzing data from a recent longitudinal clinical trial in N = 44 abstinent treatment-seeking alcohol-dependent patients. A follow-up was conducted over 3 months. We computed the percentage of significant voxels in VS and tested main effects and interactions with NTX treatment on relapse risk using Cox Regression models.We found a significant interaction effect between pre-treatment cue reactivity in the VS and NTX treatment on time to first heavy relapse (Hazard Ratio = 7.406, 95% CI 1.17-46.56, p = 0.033), such that the patient group with high VS activation (defined by a mean split) showed a significant medication effect (Hazard Ratio = 0.140, 95% CI 0.02-0.75, p = 0.022) with a number needed to treat of 3.4 [95% CI 2.413.5], while there was no significant effect in the group with low VS activation (Hazard Ratio = 0.726, p = 0.454).Thus, using an independent sample we replicated the previously described positive association between VS activation and NTX efficacy. Although our results should be considered cautiously in light of the small sample size, our results support the potential of neural alcohol CR as a tool for precision medicine approaches in alcohol dependence.

Naltrexone
Cue-reactivity
Relapse
Precision medicine
Alcohol addiction
FMRI


The Role of the Mechanotransduction Ion Channel Candidate Nanchung-Inactive in Auditory Transduction in an Insect Ear.

Abstract: Insect auditory receivers provide an excellent comparative resource to understand general principles of auditory transduction, but analysis of the electrophysiological properties of the auditory neurons has been hampered by their tiny size and inaccessibility. Here we pioneer patch-clamp recordings from the auditory neurons of Müller's organ of the desert locust Schistocerca gregaria to characterize dendritic spikes, axonal spikes, and the transduction current. We demonstrate that dendritic spikes, elicited by sound stimuli, trigger axonal spikes, and that both types are sodium and voltage dependent and blocked by TTX. Spontaneous discrete depolarizations summate upon acoustic stimulation to produce a graded transduction potential that in turn elicits the dendritic spikes. The transduction current of Group III neurons of Müller's organ, which are broadly tuned to 3 kHz, is blocked by three ion channel blockers (FM1-43, streptomycin, and 2-APB) that are known to block mechanotransduction channels. We investigated the contribution of the candidate mechanotransduction ion channel Nanchung-Inactive-which is expressed in Müller's organ-to the transduction current. A specific agonist of Nanchung-Inactive, pymetrozine, eliminates the sound-evoked transduction current while inducing a tonic depolarizing current of comparable amplitude. The Nanchung-Inactive ion channels, therefore, have the required conductance to carry the entire transduction current, and sound stimulation appears not to open any additional channels. The application of three mechanotransduction ion channel blockers prevented the pymetrozine-induced depolarizing current. This implies that either Nanchung-Inactive is, or forms part of, the mechanotransduction ion channel or it amplifies a relatively small current (<30 pA) produced by another mechanotransduction ion channel such as NompC.SIGNIFICANCE STATEMENT The mechanically activated ion channel underpinning hearing is not known. We have pioneered intracellular patch-clamp recordings from locust auditory neurons to unravel the role of the candidate mechanotransduction ion channel Nanchung-Inactive in auditory transduction in insects.

D050051:Transient Receptor Potential Channels

mechanotransduction ion channel
auditory transduction
desert locust
hearing
chordotonal organ
receptor current


4-Hydroxycinnamic acid suppresses airway inflammation and mucus hypersecretion in allergic asthma induced by ovalbumin challenge.

Abstract: In this study, we investigated whether 4-hydroxycinnamic acid (HA) has a palliative effect on asthmatic inflammatory responses using a mouse model of ovalbumin (OVA)-induced allergic asthma. The mice were divided into five groups, each consisting of seven females (normal control phosphate-buffered saline); OVA (OVA sensitization/challenge); dexamethasone (DEX, OVA sensitization/challenge + dexamethasone 3 mg/kg); HA-10 and HA-20 OVA sensitization/challenge + HA 10 and 20 mg/kg, respectively). Mice treated with HA showed a reduction in airway hyperresponsiveness and in the number of inflammatory cells in bronchoalveolar lavage fluid (BALF) compared with asthmatic control. HA treatment also reduced the levels of interleukin (IL)-5 and IL-13 in BALF and of OVA-specific immunoglobulin E in the serum compared with asthmatic control. HA treatment relieved airway inflammation and mucus overproduction caused by OVA exposure. Additionally, HA inhibited the increases in levels of nuclear factor kappa B, inducible nitric oxide synthase, and cyclooxygenase-2 that normally occur after OVA exposure. HA treatment also reduced the activity and protein level of matrix metalloproteinase-9. Taken together, HA effectively suppressed asthmatic airway inflammation and mucus production caused by OVA exposure. These findings indicate that HA has the potential to be used as a therapeutic agent for asthma.

inflammation
asthma
nuclear factor kappa B
metalloproteinase-9
4-hydroxycynnamic acid


Assessing Measles Transmission in the United States Following a Large Outbreak in California.

Abstract: The recent increase in measles cases in California may raise questions regarding the continuing success of measles control. To determine whether the dynamics of measles is qualitatively different in comparison to previous years, we assess whether the 2014-2015 measles outbreak associated with an Anaheim theme park is consistent with subcriticality by calculating maximum-likelihood estimates for the effective reproduction numbe given this year's outbreak, using the Galton-Watson branching process model. We find that the dynamics after the initial transmission event are consistent with prior transmission, but does not exclude the possibilty that the effective reproduction number has increased.

Blumberg|Seth|S| Worden|Lee|L| Enanoria|Wayne|W| Ackley|Sarah|S| Deiner|Michael|M| Liu|Fengchen|F| Gao|Daozhou|D| Lietman|Thomas|T| Porco|Travis|T|

Measles
effective reproduction number
infectious diseases
transmission chain


Should we start integrating genetic data in decision-making on device-aided therapies in Parkinson disease? A point of view.

Abstract: Parkinson disease (PD) is a complex heterogeneous neurodegenerative disorder. Association studies have revealed numerous genetic risk loci and variants, and about 5-10% suffer from a monogenic form. Because the presentation and course of PD is unique to each patient, personalized symptomatic treatment should ideally be offered to treat the most disabling motor and non-motor symptoms. Indeed, clinical milestones and treatment complications that appear during disease progression are influenced by the genetic imprint. With recent advances in PD, more patients live longer to become eligible for device-aided therapies, such as apomorphine continuous subcutaneous infusion, levodopa duodenal gel infusion, and deep brain stimulation surgery, each with its own inclusion and exclusion criteria, advantages and disadvantages. Because genetic variants influence the expression of particular clinical profiles, factors for better or worse outcomes for device-aided therapies may then be proactively identified. For example, mutations in PRKN, LRRK2 and GBA express phenotypes that favor suitability for different device therapies, although with marked differences in the therapeutic window; whereas multiplications of SNCA express phenotypes that make them less desirable for device therapies.

Salles|Philippe A|PA|
Mata|Ignacio F|IF|
Fernandez|Hubert H|HH|

Apomorphine continuous subcutaneous infusion


Inactivation effect and mechanisms of combined ultraviolet and metal-doped nano-TiO2 on treating Escherichia coli and Enterococci in ballast water.

Abstract: The discharge of ship ballast water (containing large amounts of alien organisms) has caused severe ecological hazards to marine environments. In this study, three metal elements (Ag, Fe, and Gd) were doped to nano-TiO2 material respectively (content: 0.4%, 0.7%, and 1.0%) to improve inactivation effect of Escherichia coli and Enterococci in ballast water. Experimental results indicate that compared with the sole ultraviolet (UV) and the UV and original nano-TiO2, the UV and metal-doped nano-TiO2 increased the bacterial inactivation rate to different extents. For each metal element, high external metal content (1.0%) corresponded to high inactivation effort. The doping of Ag resulted in optimal inactivation effort, and the addition of Fe and Gd caused unobvious effort. At the end of the inactivation process (20 s), the UV and 1% Ag-doped nano-TiO2 reached the highest logarithmic sterilization rates (0.915 for Escherichia coli and 0.805 for Enterococcus). The doping of Ag, Fe, and Gd did not change the anatase phase TiO2 crystal form, and 1% Ag-doped nano-TiO2 had the smallest particle diameter and the evenest distribution of nanoparticles. Compared with the sole UV, the UV and Ag-doped nano-TiO2 treatment resulted in higher malondialdehyde contents (0.0646 μmol/L for Escherichia coli and 0.0529 μmol/L for Enterococci) and lower superoxide dismutase activities (0.672 U/mL for Escherichia coli and 0.792 U/mL for Enterococci), which were in accordance with high inactivation rates in these cases.

Wang|Xixi|X| Huang|Yanli|Y| Zhang|Kun|K| Shi|Yue|Y| Lu|Zheng|Z| Wang|Yinhao|Y|

Inactivation
Metal-doped nano-TiO2
Ship ballast water
Malondialdehyde (MDA)
Material characteristics
Superoxide dismutase (SOD)


Extending the story of very-long-chain fatty acid elongation.

Abstract: Very-long-chain fatty acids (VLCFAs) are essential molecules produced by all plant cells, and are components or precursors of numerous specialized metabolites synthesized in specific cell types. VLCFAs are elongated by an endoplasmic reticulum-localized fatty acid elongation complex of four core enzymes, which sequentially add two carbon units to a growing acyl chain. Identification and characterization of these enzymes in Arabidopsis thaliana has revealed that three of the four enzymes act as generalists, contributing to all metabolic pathways that require VLCFAs. A fourth component, the condensing enzyme, provides substrate specificity and determines the amount of product synthesized by the entire complex. Land plants have two families of condensing enzymes, FATTY ACID ELONGATION 1 (FAE1)-type ketoacyl-CoA synthases (KCSs) and ELONGATION DEFECTIVE-LIKEs (ELO-LIKEs). Our current knowledge of the specific roles of different condensing enzymes is incomplete, as is our understanding of the biological function of a recently characterized family of proteins, CER2-LIKEs, which contribute to condensing enzyme function. More broadly, the stoichiometry and quaternary structure of the fatty acid elongase complex remains poorly understood, and specific phylogenetic and biochemical questions persist for each component of the complex. Investigation of VLCFA elongation in different organisms, structural biochemistry, and cell biology approaches stand to greatly benefit this field of plant biology.

D000123:Acetyltransferases
D017360:Arabidopsis
D019669:Embryophyta
D004721:Endoplasmic Reticulum
D000081031:Fatty Acid Elongases
D005227:Fatty Acids
D008958:Models, Molecular
D009097:Multienzyme Complexes
D010940:Plant Proteins
D013379:Substrate Specificity

Very-long-chain fatty acid
Very-long-chain fatty acid
VLCFA
Arabidopsis thaliana
Condensing enzymes
KETOACYL-COA SYNTHASE
CER2-LIKEs
Fatty acid elongase complex
ACP
CER2
CoA
ECERIFERUM2
ECR
ELO
ELONGATION DEFECTIVE
ENOYL-COA REDUCTASE
HCD
HYDROXYACYL-COA DEHYDRATASE
KCR
KCS
KETOACYL-COA REDUCTASE
LACS
LONG-CHAIN ACYL-COENZYME A SYNTHETASE
acyl carrier protein
coenzyme A
very-long-chain fatty acid

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


The inter-rater reliability of the modified finger goniometer for measuring forearm rotation.

Abstract:
STUDY DESIGN
Prospective cohort study.

PURPOSE OF THE STUDY
To compare the inter-rater reliability of using a modified finger goniometer (MFG) for the measurement of isolated forearm rotation for patients with distal radius fractures to the currently accepted technique for isolated forearm measurement.

INTRODUCTION
The currently accepted method of forearm measurement requires the assessor to visually estimate vertical for the stationary arm and placement of the moveable arm while placing a straight edge along a curved surface. Inter-rater reliability may be limited as assessors may estimate the placement of the goniometer arms differently depending on their experience, posture, and even their positioning relative to the patient. Rather than continue to place a straight edge on a round surface, we evaluate a new technique using an MFG for measuring isolated forearm rotation.

METHODS
Patients with clinically healed distal radius fractures were enrolled in the study. Measurement of active forearm pronation and supination was recorded using 2 separate measurement techniques. These measurements were taken by 2 separate hand therapists with more than 10 years of clinical experience in a tertiary care setting at the beginning and end of hand therapy sessions for 3 consecutive weekly visits. Intraclass correlation coefficients (ICCs), standard error of measurement, and minimal detectable change were calculated for each technique.

RESULTS
The point estimates for the MFG method demonstrated a slightly higher ICC than the standard method for pronation (0.86 vs 0.82). For supination, both measurement techniques displayed equally high pooled ICCs (0.95). The standard error of measurements for the MFG were 2.1 for pronation and 1.2 for supination compared with 2.9 (pronation) and 1.2 (supination) for the standard technique. These translate into 90% minimal detectable changes of 5° and 3° for the MFG pronation/supination compared with 7° (pronation) and 3° (supination) for the standard technique, respectively.

DISCUSSION
Although the point estimates for the ICCs of the MFG method are equal or higher than the standard method, the confidence intervals for the ICCs overlap, indicating that the MFG is at least equivalent to the standard method in terms of inter-rater reliability.

LEVEL OF EVIDENCE
2b.

Szekeres|Mike|M|
MacDermid|Joy C|JC|
Birmingham|Trevor|T|
Grewal|Ruby|R|

Measurement
Forearm rotation
Distal radius fracture
Goniometry