sIL-24 peptide, a human interleukin-24 isoform, induces mitochondrial-mediated apoptosis in human cancer cells.

Abstract:
PURPOSE
Interleukin-24 (IL-24) is a unique cytokine in the IL-10 family that reveals tumor-suppressive activity against a broad range of cancers. Alternative splicing of human IL-24 generates several isoforms with different pro-apoptotic activities. In the current study, we aimed to investigate the cytotoxic properties of a recombinant smallest isoform of IL-24 (sIL-24) and the underlying molecular mechanisms in PC-3, A549, U937, and Raji cancer cells as well as normal cell line MRC-5.

METHODS
Following treatment of the cells with recombinant sIL-24 peptide and full-length IL-24 protein, cytotoxicity was determined by MTT assay. Apoptosis induction was evaluated using annexin-V/PI double staining flow cytometry and Hoechst 33342 staining. The expression of Bax, Bcl-2, cytochrome c, and caspase-3 was analyzed by Western blotting.

RESULTS
MTT assay exhibited that sIL-24 dose and time dependently inhibited the proliferation of IL-24 receptor-positive PC-3, U937, and Raji cells more effectively than full-length IL-24. In contrast, sIL-24 had little cytotoxic effect on A549 cells lacking the IL-24 receptor, or on MRC-5 normal cells. Flow cytometric analysis and morphological observation revealed an efficient apoptosis induction in the receptor-positive cells. Furthermore, Western blot assay demonstrated that cell death induced by sIL-24 was associated with upregulation of the Bax/Bcl-2 ratio, cytochrome c release, and the expression of cleaved caspase-3, suggesting that sIL-24 induced apoptosis mainly through the mitochondrial pathway. Notably, among the tested cells, induction of apoptosis was more significant in PC-3 cells.

CONCLUSION
Our results suggest that the sIL-24 peptide is a promising candidate for potential treatment of human cancers.

Valiyari|Samira|S|
Salami|Mona|M|
Mahdian|Reza|R|
Shokrgozar|Mohammad Ali|MA|
Oloomi|Mana|M|
Mohammadi Farsani|Azadeh|A|
Bouzari|Saeid|S|

sIL-24 peptide
Apoptosis
Cytotoxicity
Anticancer


Prevention of incisional hernia at the site of stoma closure with different reinforcing mesh types: a systematic review and meta-analysis.

Abstract:
PURPOSE
To evaluate safety and efficacy of a mesh reinforcement following stoma reversal to prevent stoma site incisional hernia (SSIH) and differences across the prostheses used.

METHODS
A systematic search of PubMed/MEDLINE, EMBASE, SCOPUS and Cochrane databases was conducted to identify comparative studies until September 2020. A meta-analysis of postoperative outcomes and a network meta-analysis for a multiple comparison of the prostheses with each other were performed.

RESULTS
Seven studies were included in the analysis (78.4% ileostomy and 21.6% colostomy) with a total of 1716 patients with (n = 684) or without (n = 1032) mesh. Mesh placement was associated with lower risk of SSIH (7.8%vs18.1%, OR0.266,95% CI 0.123-0.577, p < 0.001) than no mesh procedures but also with a longer operative time (SMD 0.941, 95% CI 0.462-1.421, p < 0.001). There was no statistically significant difference in terms of Surgical Site infection (11.5% vs 11.1%, OR 1.074, 95% CI 0.78-1.48, p = 0.66), seroma formation (4.4% vs 7.1%, OR 1.052, 95% CI 0.64-1.73, p = 0.84), anastomotic leakage (3.7% vs 2.7%, OR 1.598, 95% CI 0.846-3.019, p = 0.149) and length of stay (SMD - 0.579,95% CI - 1.261 to 0.102, p = 0.096) between mesh and no mesh groups. Use of prosthesis was associated with a significant lower need for a reoperation than no mesh group (8.1% vs 12.1%, OR 0.332, 95% CI 0.119-0.930, p = 0.036). Incidence of seroma is lower with biologic than polypropylene meshes but they showed a trend towards poor results compared with polypropylene or biosynthetic meshes.

CONCLUSION
Despite longer operative time, mesh prophylactic reinforcement at the site of stoma seems a safe and effective procedure with lower incidence of SSIH, need for reoperation and comparable short-term outcomes than standard closure technique. A significant superiority of a specific mesh type was not identified.

Peltrini|Roberto|R|0000-0003-0445-2269
Imperatore|Nicola|N|
Altieri|Gaia|G|
Castiglioni|Simone|S|
Di Nuzzo|Maria Michela|MM|
Grimaldi|Luciano|L|
D'Ambra|Michele|M|
Lionetti|Ruggero|R|
Bracale|Umberto|U|
Corcione|Francesco|F|

D059685:Herniorrhaphy
D006801:Humans
D000069290:Incisional Hernia
D019736:Prostheses and Implants
D013526:Surgical Mesh
D054047:Surgical Stomas

Prevention
Incisional hernia
Stoma reversal
Biologic mesh
Synthetic mesh


Simultaneous multislice refocusing via time optimal control.

Abstract:
PURPOSE
Joint design of minimum duration RF pulses and slice-selective gradient shapes for MRI via time optimal control with strict physical constraints, and its application to simultaneous multislice imaging.

THEORY AND METHODS
The minimization of the pulse duration is cast as a time optimal control problem with inequality constraints describing the refocusing quality and physical constraints. It is solved with a bilevel method, where the pulse length is minimized in the upper level, and the constraints are satisfied in the lower level. To address the inherent nonconvexity of the optimization problem, the upper level is enhanced with new heuristics for finding a near global optimizer based on a second optimization problem.

RESULTS
A large set of optimized examples shows an average temporal reduction of 87.1% for double diffusion and 74% for turbo spin echo pulses compared to power independent number of slices pulses. The optimized results are validated on a 3T scanner with phantom measurements.

CONCLUSION
The presented design method computes minimum duration RF pulse and slice-selective gradient shapes subject to physical constraints. The shorter pulse duration can be used to decrease the effective echo time in existing echo-planar imaging or echo spacing in turbo spin echo sequences.

Rund|Armin|A|
Aigner|Christoph Stefan|CS|
Kunisch|Karl|K|
Stollberger|Rudolf|R|

refocusing
time optimal control
pulse design
simultaneous multislice excitation


Involvement of FGF-2 modulation in the antidepressant-like effects of liquiritin in mice.

Abstract: It has been reported that liquiritin produced an antidepressant-like effect in rodents. However, little information is known regarding its antidepressant activity with the regulation of fibroblast growth factor 2 (FGF-2), a protein maintaining development and maturation of the nervous central system. Therefore, the aim of the present study was to investigate the underlying FGF-2 modulation involved in the antidepressant-like effects of liquiritin. In the present study, mice were orally administrated with liquiritin for 7 days prior to LPS injection. The depressive-like behaviors, levels of FGF-2, number of Iba1 positive cells, expression of proinflammatory cytokines and density of dendritic spines were evaluated. The results showed that liquiritin significantly ameliorated the depressive-like behaviors in mice response to LPS injection. Liquiritin reversed the reduction of FGF-2 levels in the hippocampus of LPS induced mice. In addition, the microglial activation caused by LPS was attenuated by liquiritin, in accordance with downregulation in mRNA levels of proinflammatory cytokines. Moreover, liquiritin also increased the density of dendritic spines in the hippocampus, which was suppressed by LPS. In conclusion, our findings demonstrated that liquiritin exerted the antidepressant-like effects in LPS-induced depression through FGF-2 enhancement by inhibiting neuroinflammation and maintaining synaptogenesis.

Chen|Min|M| Zhang|Qiu-Ping|QP| Zhu|Ji-Xiao|JX| Cheng|Jie|J| Liu|Qing|Q| Xu|Guang-Hui|GH| Li|Cheng-Fu|CF| Yi|Li-Tao|LT|

FGF-2 Liquiritin Antidepressant Synaptogenesis Microglia


Risk Factors for Residual Disease in Hysterectomy Specimens After Conization in Post-Menopausal Patients with Cervical Intraepithelial Neoplasia Grade 3.

Abstract:
Background
Post-menopausal patients with cervical intraepithelial neoplasia (CIN) have a high rate of residual or recurrent lesions after treatment, and their risk for cervical cancer later in life is higher than the general population. Hence, management for this specific group of post-menopausal patients needs more attention.

Objective
The study aimed to identify risk factors associated with the presence of residual disease in hysterectomy specimens in post-menopausal patients with cervical intraepithelial neoplasia grade 3 (CIN 3).

Methods
This study was a retrospective analysis of data from post-menopausal women who had undergone hysterectomy following conization for CIN 3 from 2012 to 2018 at Fujian Maternity and Child Health Hospital. Factors extracted from the database included age, parity, Thinprep cytology results, human papillomavirus (HPV) genotype, biopsy results, pre-cone endocervical curettage (ECC) results, conization method, operating surgeon, cone dimension, margin status and glandular involvement. Univariate and multivariate analyses were performed to identify risk factors associated with residual disease in hysterectomy specimens.

Results
Analysis of data from 129 women was performed. The proportion of residual disease was 43.41% overall. A higher grade according to colposcopy biopsy, abnormal pre-cone ECC results, the cone method (LEEP vs CKC), a cone volume >1.57 cm3, and positive margins in conization specimens were found to be significantly associated with residual lesions on univariable analysis. After multivariate analysis, only an abnormal pre-cone ECC result (odds ratio 3.99; 95% confidence interval (CI) 1.41-11.33; p = 0.009) remained significant.

Conclusion
The rate of residual lesions in uterine specimens was high regardless of the cone margin status in post-menopausal women with CIN 3. Risk-based strategies are needed to identify patients who have abnormal pre-cone ECC results, and definitive treatment with hysterectomy should be considered in post-menopausal patients with an elevated risk for residual lesions.

endocervical curettage
margin status
cervical intraepithelial lesion
menopause


Neurosurgery in times of a pandemic: a survey of neurosurgical services during the COVID-19 outbreak in the Veneto region in Italy.

Abstract:
OBJECTIVE
The purpose of this study was to analyze the effect of the coronavirus disease 2019 (COVID-19) outbreak and of the subsequent lockdown on the neurosurgical services of the Veneto region in Italy compared to the previous 4 years.

METHODS
A survey was conducted in all 6 neurosurgical departments in the Veneto region to collect data about surgical, inpatient care and endovascular procedures during the month of March for each year from 2016 to 2020. Safety measures to avoid infection from SARS-CoV-2 and any COVID-19 cases reported among neurosurgical patients or staff members were considered.

RESULTS
The mean number of neurosurgical admissions for the month of March over the 2016-2019 period was 663, whereas in March 2020 admissions decreased by 42%. Emergency admissions decreased by 23%. The average number of neurosurgical procedures was 697, and declined by 30% (range -10% to -51% in individual centers). Emergency procedures decreased in the same period by 23%. Subarachnoid hemorrhage and spontaneous intracerebral hemorrhage both decreased in Veneto-by 25% and 22%, respectively. Coiling for unruptured aneurysm, coiling for ruptured aneurysm, and surgery for ruptured aneurysm or arteriovenous malformation diminished by 49%, 27%, and 78%, respectively. Endovascular procedures for acute ischemic stroke (AIS) increased by 33% in 2020 (28 procedures in total). There was a slight decrease (8%) in brain tumor surgeries. Neurosurgical admissions decreased by 25% and 35% for head trauma and spinal trauma, respectively, while surgical procedures for head trauma diminished by 19% and procedures for spinal trauma declined by 26%. Admissions and surgical treatments for degenerative spine were halved. Eleven healthcare workers and 8 patients were infected in the acute phase of the pandemic.

CONCLUSIONS
This multicenter study describes the effects of a COVID-19 outbreak on neurosurgical activities in a vast region in Italy. Remodulation of neurosurgical activities has resulted in a significant reduction of elective and emergency surgeries compared to previous years. Most likely this is a combined result of cancellation of elective and postponable surgeries, increase of conservative management, increase in social restrictions, and in patients' fear of accessing hospitals. Curiously, only endovascular procedures for AIS have increased, possibly due to reduced physical activity or increased thrombosis in SARS-CoV-2. The confounding effect of thrombectomy increase over time cannot be excluded. No conclusion can be drawn on AIS incidence. Active monitoring with nasopharyngeal swabs, wearing face masks, and using separate pathways for infected patients reduce the risk of infection.

Raneri|Fabio|F|
Rustemi|Oriela|O|
Zambon|Giampaolo|G|
Del Moro|Giulia|G|
Magrini|Salima|S|
Ceccaroni|Yuri|Y|
Basso|Elisabetta|E|
Volpin|Francesco|F|
Cappelletti|Martina|M|
Lardani|Jacopo|J|
Ferraresi|Stefano|S|
Guida|Franco|F|
Chioffi|Franco|F|
Pinna|Giampietro|G|
Canova|Giuseppe|G|
d'Avella|Domenico|D|
Sala|Francesco|F|
Volpin|Lorenzo|L|

neurosurgery pandemic COVID-19 SARS-CoV-2 emergency surgery


Combination therapies plus transarterial chemoembolization in hepatocellular carcinoma: a snapshot of clinical trial progress.

Abstract:
INTRODUCTION
Unfortunately, some hepatocellular carcinoma (HCC) patients do not qualify for curative-intent treatments such as surgical resection or transplantation. Hence, locoregional treatments such as transarterial chemoembolization (TACE) remain instrumental in the treatment of HCC. Systemic therapy has improved over the past decade with the introduction of combination atezolizumab and bevacizumab as the new standard of care for advanced disease. These new therapies are currently under investigation in combination with TACE.

AREA COVERED
Combination therapies with TACE including systemic therapies, locoregional therapies, and immunotherapies are reviewed.

EXPERT OPINION
There has been limited progress in the management of advanced and intermediate HCC. Recent advances in the management of advanced disease with systemic therapy could be beneficial in combination with TACE for the treatment of intermediate stage disease. Immune based therapies are potentially beneficial in combination with TACE because TACE may produce increased antigen release and immune recognition.

Brown|Zachary J|ZJ|
Hewitt|D Brock|DB|
Pawlik|Timothy M|TM|

transarterial chemoembolization
Hepatocellular carcinoma
locoregional therapy
immunotherapy
radiofrequency ablation


Exploratory study into the relationship between the symptoms of chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME) and fibromyalgia (FM) using a quasiexperimental design.

Abstract:
OBJECTIVE
To explore the relationship between symptoms of chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME) and fibromyalgia (FM). The hypothesis predicated that there would be no significant differences between the group's symptom experience.

DESIGN
A quasiexperimental design. Structural equation modelling (SEM) and invariance testing.

PARTICIPANTS
Males (M) and females (F) >16 with a confirmed diagnosis of CFS/ME or FM by a general practitioner or specialist. CFS/ME (n=101, F: n=86, M: n=15, mean (M) age M=45.5 years). FM (n=107, F: n=95, M: n=12, M=47.2 years).

OUTCOME MEASURES
Diagnostic criteria: the American Centers for Disease Control and Prevention (CDC) for CFS/ME and the American College of Rheumatology (ACR) criteria for FM. Additional symptom questionnaires measuring: pain, sleep quality, fatigue, quality of life, anxiety and depression, locus of control and self-esteem.

RESULTS
Invariance was confirmed with the exception of the American CDC Symptom Inventory, Fibromyalgia Impact Questionnaire and Hospital Anxiety and Depression Scale (p<0.05) based on five questions. Consequently, it was erroneous to conclude differences. Therefore, the Syndrome Model was created. SEM could not have tested the ACR previously, as it comprised a single data point. Thus, it was combined with these three questionnaires, increasing the data points, to create this new measurable model. Results confirmed no significant differences between groups (p=0.07 (p<0.05)).

CONCLUSION
Participants responded in a similar manner to the questionnaire, confirming the same symptom experience. It is important to consider this in context with differing criteria and management guidelines, as this may influence diagnosis and the trajectory of patient's management. With the biomedical cause currently unclear, it is the symptom experience and the impact on quality of life that is important. These findings are meaningful for patients, clinicians and policy development and support the requirement for future research.

Mckay|Pamela G|PG|0000-0002-1544-4662
Walker|Helen|H|
Martin|Colin R|CR|
Fleming|Mick|M|

chronic fatigue syndrome
fibromyalgia
pain
sleep
myalgic encephalomyelitis


Absence of cGAS-mediated type I IFN responses in HIV-1-infected T cells.

Abstract: The DNA sensor cGAS catalyzes the production of the cyclic dinucleotide cGAMP, resulting in type I interferon responses. We addressed the functionality of cGAS-mediated DNA sensing in human and murine T cells. Activated primary CD4+ T cells expressed cGAS and responded to plasmid DNA by upregulation of ISGs and release of bioactive interferon. In mouse T cells, cGAS KO ablated sensing of plasmid DNA, and TREX1 KO enabled cells to sense short immunostimulatory DNA. Expression of IFIT1 and MX2 was downregulated and upregulated in cGAS KO and TREX1 KO T cell lines, respectively, compared to parental cells. Despite their intact cGAS sensing pathway, human CD4+ T cells failed to mount a reverse transcriptase (RT) inhibitor-sensitive immune response following HIV-1 infection. In contrast, infection of human T cells with HSV-1 that is functionally deficient for the cGAS antagonist pUL41 (HSV-1ΔUL41N) resulted in a cGAS-dependent type I interferon response. In accordance with our results in primary CD4+ T cells, plasmid challenge or HSV-1ΔUL41N inoculation of T cell lines provoked an entirely cGAS-dependent type I interferon response, including IRF3 phosphorylation and expression of ISGs. In contrast, no RT-dependent interferon response was detected following transduction of T cell lines with VSV-G-pseudotyped lentiviral or gammaretroviral particles. Together, T cells are capable to raise a cGAS-dependent cell-intrinsic response to both plasmid DNA challenge or inoculation with HSV-1ΔUL41N. However, HIV-1 infection does not appear to trigger cGAS-mediated sensing of viral DNA in T cells, possibly by revealing viral DNA of insufficient quantity, length, and/or accessibility to cGAS.


Rate of reoperation at 1 year for aortic repair vs replacement in aortic regurgitation. A trial sequence analysis of published meta-analysis results.

Abstract: The pooled estimate of a recent meta-analysis concluded that rate of reoperation at 1 year was significantly higher in Aortic valve repair (8.82% vs 3.70%) as compared with aortic valve replacement in patients with aortic regurgitation (odds ratio = 2.67, 95% confidence interval [1.08, 3.62], P = .03). We performed a trial sequential analysis using the published data of the meta-analysis and found the evidence is not strong enough for the conclusion.

D019918:Heart Valve Prosthesis Implantation

aortic regurgitation
aortic valve repair
aortic valve replacement
trial sequential analysis


The liver in times of COVID-19: What hepatologists should know.

Abstract: The ongoing pandemic of coronavirus disease 2019 (COVID-19) pandemic poses a serious threat to healthcare systems globally. Information regarding how the infection affects the liver and relevance of pre-existing liver disease as a risk factor for acquiring the infection or having a severe disease are still scarce. Also, considerations in liver transplant patients, those having hepatocellular carcinoma or under immunosuppressive therapy are being matter of analysis as information is being generated. Different treatments for COVID-19 are currently under study, some of which may be associated to hepatotoxicity. In the present review we discuss current data on the COVID-19 and liver, aiming to provide hepatologists with updated information to face this pandemic.

Coronavirus
Liver disease
Transplantation
Cirrhosis
SARS-CoV-2


Gender differences in audio-vestibular disorders.

Abstract: In the last years, the attention to the role of gender in physiopathology and pharmacology of diseases in several medical disciplines is rising; however, the data on the relationship between gender and audio-vestibular disorders are still inconclusive and sometimes confusing. With this letter to the editor, we would like to review the role of gender in audio-vestibular disorders. Literature data show that anatomic variances of the inner ear do exist in men and women and that the different physiology and/or hormonal influence between genders could produce different clinical outcome of routine audiological and vestibular tests. Beyond the epidemiological gender-related differences, the clinical data suggest that the gender has a potential role as an etiopathogenetic factor in audio-vestibular disorders and it is probably responsible for the different clinical features observed between male and female subjects.

gender
gender differences
inner ear
audiology
cochlea
sensorineural hearing loss
sex
vestibule


GPR39-1b, the 5-transmembrane isoform of GPR39 interacts with neurotensin receptor NTSR1 and modifies its function.

Abstract: G-protein-coupled receptor 39 (GPR39), a member of the ghrelin receptor family, has a full-length isoform GPR39-1a and a truncated isoform GPR39-1b. While GPR39-1a was clarified as a receptor of Zn(2+), the characteristic property of GPR39-1b remains unknown. Therefore, in this study, the molecular functions of GPR39-1b were explored in cell culture. In contrast to GPR39-1a, GPR39-1b showed no response to Zn(2+) stimulation in calcium mobilization assays, suggesting that GPR39-1b is not a functional receptor of Zn(2+). To understand the signaling interaction of GPR39-1b, we investigated the dimerization between the isoforms, and conducted bioluminescence resonance energy transfer (BRET(2)) assays. The results indicated that GPR39-1b homodimerized, but did not heterodimerize with GPR39-1a. We subsequently attempted to search the heterodimeric counterparts of GPR39-1b. Neurotensin receptor 1 (NTSR1) was also targeted as a GPR39-1b interacting partner because of its highly conserved amino acid sequence and mRNA localization, which was similar to GPR39-1b. BRET(2) assays demonstrated that GPR39-1b heterodimerized with NTSR1. To examine the effect of GPR39-1b on NTRS1-mediated cAMP/PKA signaling, we used the cAMP responsive element-luciferase assays and observed that GPR39-1b attenuated neurotensin-induced NTSR1 signaling. Taken together, our results provided a novel regulatory mechanism for GPR39-1b in NTRS1 signaling.

D060807:Bioluminescence Resonance Energy Transfer Techniques

GPR39
neurotensin
NTSR1
G-protein-coupled receptor
heterodimerization
BRET


Chemosensory proteins participate in insecticide susceptibility in Rhopalosiphum padi, a serious pest on wheat crops.

Abstract: Rhopalosiphum padi is a worldwide agricultural pest. Chemosensory proteins (CSPs) are considered to be a type of transporters which can bind chemicals from external environments. Previous research showed that the expression of some insect CSPs were significantly increased after exposure to insecticides, and CSPs were involved in insecticide resistance or susceptibility. However, the role of CSPs in the susceptibility and response of R. padi to insecticides is still unknown. In this study, we identified eight CSP (RpCSP) from R. padi by genome-wide investigation. Seven RpCSP genes had two exons, while RpCSP7 had three exons. qPCR analyses showed that the mRNA levels of the eight RpCSP genes were significantly affected by imidacloprid and beta-cypermethrin in different post-treatment periods. Molecular docking predicted that there were hydrogen bonding sites which played key roles in binding of RpCSP4, RpCSP5, RpCSP6, RpCSP7 and RpCSP10 with imidacloprid and beta-cypermethrin. Knockdown of RpCSP4, RpCSP5, RpCSP6 and RpCSP10 by RNA interference significantly increased the aphid mortality under two sublethal concentrations of imidacloprid. Mortalities under two sublethal concentrations of beta-cypermethrin conditions were significantly higher after injection of R. padi with dsCSP4 and dsCSP6. The results indicate that some RpCSP genes are involved in the insecticide susceptibility of R. padi.

Peng|X|X|
Qu|M J|MJ|
Wang|S J|SJ|
Huang|Y X|YX|
Chen|C|C|
Chen|M H|MH|

chemosensory proteins
imidacloprid
beta-cypermethrin
molecular docking
bird cherry-oat aphid
survival rate


Baclofen effects on alcohol seeking, self-administration and extinction of seeking responses in a within-session design in baboons.

Abstract: Baclofen, a gamma-aminobutyric acidB receptor agonist, is currently under investigation as a potential treatment to prevent relapse to drinking in alcohol-dependent persons. In the current study, two groups of baboons were trained under a chained schedule of reinforcement (CSR), with three linked components, which were each correlated with different response requirements and cues. Fulfilling the requirement in the second link initiated the third link where either alcohol (n = 4) or a preferred non-alcoholic beverage (Tang, n = 5) was available for self-administration; failure to complete the response requirement in Link 2 ended the session (no access to alcohol or Tang). Seeking responses in Link 2 were used as indices of the motivational processes thought to be involved in relapse. The effects of baclofen (0.1-2.4 mg/kg) were examined under conditions with alcohol or Tang access and under extinction. Under the CSR, baclofen (1.8 and 2.4 mg/kg) significantly decreased (P < 0.05) alcohol self-administration responses and total g/kg alcohol intake. In contrast, only the highest dose of baclofen (2.4 mg/kg) reduced Tang self-administration and consumption. Under within-session extinction conditions, baclofen (1.8 and 2.4 mg/kg) facilitated extinction of responding for both alcohol and Tang, particularly during the first 10 minutes of extinction. Baclofen may be effective in reducing craving and alcohol drinking, although the facilitation of extinction and suppression of both alcohol and Tang self-administration by baclofen suggests these effects may be related to a more general suppression of consummatory and conditioned behaviors.

Duke|Angela N|AN|
Kaminski|Barbara J|BJ|
Weerts|Elise M|EM|

baclofen
Alcohol
extinction
reinforcement
drug-seeking
non-human primate


C9orf72, a protein associated with amyotrophic lateral sclerosis (ALS) is a guanine nucleotide exchange factor.

Abstract: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two late onset neurodegenerative diseases, have been shown to share overlapping cellular pathologies and genetic origins. Studies suggest that a hexanucleotide repeat expansion in the first intron of the C9orf72 gene is the most common cause of familial FTD and ALS pathology. The C9orf72 protein is predicted to be a differentially expressed in normal and neoplastic cells domain protein implying that C9orf72 functions as a guanine nucleotide exchange factor (GEF) to regulate specific Rab GTPases. Reported studies thus far point to a putative role for C9orf72 in lysosome biogenesis, vesicular trafficking, autophagy and mechanistic target of rapamycin complex1 (mTORC1) signaling. Here we report the expression, purification and biochemical characterization of C9orf72 protein. We conclusively show that C9orf72 is a GEF. The distinctive presence of both Rab- and Rho-GTPase GEF activities suggests that C9orf72 may function as a dual exchange factor coupling physiological functions such as cytoskeleton modulation and autophagy with endocytosis.

Iyer|Shalini|S|
Subramanian|Vasanta|V|
Acharya|K Ravi|KR|0000-0002-3009-4058

C9orf72
ALS
Guanine nucleotide exchange factor
Rab GTPases
Neurodegeneration
Protein expression
Protein purification
Size-exclusion chromatography


In vitro surrogate models to aid in the development of antivirals for the containment of foot-and-mouth disease outbreaks.

Abstract: Foot-and-mouth disease virus (FMDV) is a highly pathogenic member of the genus Aphthovirus (family Picornaviridae) that is only to be manipulated in high-containment facilities, thus complicating research on and discovery of antiviral strategies against the virus. Bovine rhinitis B virus (BRBV) and equine rhinitis A virus (ERAV), phylogenetically most closely related to FMDV, were explored as surrogates for FMDV in antiviral studies. Although no efficient cell culture system has been reported so far for BRBV, we demonstrate that infection of primary bovine kidney cells resulted in an extensive but rather poorly-reproducible induction of cytopathic effect (CPE). Madin-Darby bovine kidney cells on the other hand supported viral replication in the absence of CPE. Antiviral tests were developed for ERAV in Vero A cells employing a viral RNA-reduction assay and CPE-reduction assay; the latter having a Z' factor of 0.83±0.07. The BRBV and ERAV models were next used to assess the anti-aphthovirus activity of two broad-spectrum antiviral agents 2'-C-methylcytidine (2CMC) and ribavirin, as well as of the enterovirus-specific inhibitor enviroxime. The effects of the three compounds in the CPE-reduction (ERAV) and viral RNA-reduction assays (BRBV and ERAV) were comparable. Akin to 2CMC, compound A, a recently-discovered non-nucleoside pan-serotype FMDV inhibitor, also inhibited the replication of both BRBV and ERAV, whereas enviroxime was devoid of activity. The BRBV and ERAV surrogate models reported here can be manipulated in BSL-2 laboratories and may facilitate studies to unravel the mechanism of action of novel FMDV inhibitors.

Osiceanu|Ana-Maria|AM|
Murao|Lyre Espada|LE|
Kollanur|Denny|D|
Swinnen|Jan|J|
De Vleeschauwer|Annebel R|AR|
Lefebvre|David J|DJ|
De Clercq|Kris|K|
Neyts|Johan|J|
Goris|Nesya|N|

Surrogate model
Antivirals
FMDV
Aphthovirus


Harnessing sediments of coastal aquaculture ponds through technosols construction for halophyte cultivation using saline water irrigation.

Abstract: The Mediterranean aquaculture has been developed mostly in brackish environment in inactive coastal salt production areas. This study aims to utilise Technosols made with aquaculture sediments for Limonium algarvense Erben cultivation. This species that has nutraceutical potential thrives in halophilic environments in the southwest of the Iberian Peninsula and in Morocco. A microcosm assay was set up with plants grown in bottom sediments (C+), commercial substrate (C-), and Technosols with amendments mixture application at 180 g/kg (Tec180) or at 360 g/kg (Tec360). These plants were irrigated with saline (assay 1) and/or with deionised water (assay 2). The bottom pond sediments, coffee wastes and the estuarine water were evaluated for diverse physicochemical parameters. Plant growth was characterised through a combined methodology using morphometric, SEM and physiological analysis. The Technosols were constructed with bottom sediments and a mixture of organic wastes used as amendments. Results revealed that the bottom sediments had low pH 3.2, Corg and extractable P and K contents, and high electroconductivity (EC) and N-NH4 concentration. The estuarine water had a neutral pH, high EC and high Cl-, HCO3-, Na+, Mg2+ and Ca2+ but low N-NO3- content. The Technosols showed a significant increase of pH, Corg, K and P and a decrease in N-NH4 and EC in comparison with sediments. Principal component analysis separated the different experiments in three groups: C-, A1 and A2 assays. The C- was highly correlated with Corg, P, K, N-NO3 parameters and total ascorbate. The A1 assay showed a strong association with Na, Ca and EC parameters, whereas the A2 assay presented a strongly correlation with plant growth. Plants from Technosols had greater development when irrigated with deionised water than under salty irrigation as opposed to plants cultivated in unamend sediments. In conclusion, these results support that highly saline sediments could be valorised through Technosols construction to cultivate plants with saline water, with potential application in the agro-food and pharmaceutical industry.

Cortinhas|Ana|A|
Caperta|Ana D|AD|
Teixeira|Generosa|G|
Carvalho|Luísa|L|
Abreu|Maria Manuela|MM|

Limonium algarvense
Wastes
Estuarine water
SEM analysis
Soil technology
Tailored soil


The association between renal function and BMD response to bisphosphonate treatment: Real-world cohort study using linked national registers.

Abstract:
BACKGROUND
Management of osteoporosis given reduced renal function is one of the largest challenges in the bone clinic.

OBJECTIVES
Identify the cut-off for renal function below which there would be no overall BMD benefit associated with bisphosphonate use. Track safety outcomes resulting in hospital encounters.

METHODS
Population-based, observational register-linked study of BMD trajectories in adults from the island of Funen (pop 465,000) as a function of estimated creatinine clearance (CKD-epi), treatment and adherence to oBP. One laboratory performed all the biochemical analyses for the area while all DXA scans were in a central facility. For inclusion, patients were required to have both a DXA scan and an eGFR measurement (CKD-EPI) within 1 year prior to their study index date. Medication Possession Ratio (MPR) was calculated from national data.

RESULTS
Out of 6176 incident BP users, 1789 had eGFR and DXA measurements at appropriate timepoints for the planned analysis, while this was the case for 3908 of 29,336 non-users. Users of oBPs exhibited progressively smaller gains in BMD with decreasing renal function. However, for CKD stage 3A and better, the annual change in BMD was significantly more positive than in the non-user group at similar levels of renal function. In non-users, the average annual change in BMD was negative but largely unaffected by renal function down to stage 3B. There were no new cases of acute renal injury, glomerulonephritis or dialysis. The rate of new kidney transplantation was zero in non-users and 0.26 per 1000 PY in the BP user population. Hypocalcaemia encounters did not differ significantly from that seen in non-users.

CONCLUSIONS
The BMD changes observed in real-world users of oBP in this population based single-clinic are consistent with those observed in the original RCTs of alendronate. We noted a gradual decrease in the absolute gains in BMD in oBP users with decreasing renal function though there was no significant interaction - largely explained by low numbers of treated patients with poor renal function - between CKD stage and adherence driven BMD change. There were no cases of acute renal injury resulting in hospital encounters. More data is needed on the efficacy and safety of bisphosphonates in CKD stage 3B to 5 and prescribers should reconsider the low use of DXA in patients with renal function impairment now that a wider range of treatment options are available.

Abrahamsen|Bo|B|
Ernst|Martin T|MT|
Smith|Christopher D|CD|
Nybo|Mads|M|
Rubin|Katrine Hass|KH|
Prieto-Alhambra|Daniel|D|
Hermann|Anne Pernille|AP|

Bisphosphonates
Osteoporosis
Bone mineral density
Epidemiology
Renal disease


Evaluating the biological functions of the prognostic genes identified by the Pathology Atlas in bladder cancer.

Abstract: The prognosis‑associated genes of urinary bladder cancer have been systematically investigated in the Pathology Atlas project based on The Cancer Genome Atlas data. However, the biological functions of most genes in bladder cancer remain unknown. The present study investigated the biological function of 12 of the most significant survival‑associated genes (ABRACL, MITD1, ZNF524, EMP1, HSPB6, CXorf38, TRIM38, ZNF182, ZNF195, SPRN, PTPN6 and LIPT1) in urothelial cancer reported by the Pathology Atlas project, with respect to cell proliferation and migration. In vitro, proliferation and migration analyses of T24 cells were performed following the transfection of the 12 prognostic genes. The results were validated with a small interfering (si)RNA library. Immunohistochemistry (IHC) analysis of clinical samples was performed to determine the association between gene expression and tumor metastasis. Furthermore, RNA sequencing was used to investigate the downstream signals. Among the 12 prognostic genes, MIT‑domain containing protein 1 (MITD1) transfection was demonstrated to inhibit T24 cell migration to a certain degree. Experiments performed with a 7‑gene siRNA library demonstrated that MITD1 knockdown markedly upregulated cell migratory abilities. Mechanistically, the influence of MITD1 on cell signal transduction was assessed via RNA sequencing. Cell migration‑associated genes, including KISS1, SPANXB1, SPINT1, PIWIL2, SNAI1, APLN and CTHRC1 were dysregulated. IHC analysis demonstrated that MITD1 protein expression was notably lower in metastatic lymph nodes compared with the primary tumors. Taken together, the results of the present study suggest that the prognostic gene, MITD1 may serve as a migration inhibitor, and be developed as a potential therapeutic target for improving the prognosis of bladder cancer.

Chen|Yuanbin|Y| Xu|Ting|T| Xie|Fei|F| Wang|Liping|L| Liang|Zhijuan|Z| Li|Dan|D| Liang|Ye|Y| Zhao|Kaidong|K| Qi|Xiangjie|X| Yang|Xuecheng|X| Jiao|Wei|W|

migration
prognostic  genes
Pathology  Atlas
bladder  cancer


Validation of the Verogen ForenSeq™ DNA Signature Prep kit/Primer Mix B for phenotypic and biogeographical ancestry predictions using the Micro MiSeq® Flow Cells.

Abstract: In anticipation of offering phenotypic and biogeographical ancestry predictions to help resolve cases, the Verogen ForenSeq™ DNA Signature Prep kit/Primer Mix B was evaluated in the context of Micro MiSeq® Flow Cells. These flow cells were determined as the best format for a quick turnaround time response and cost effective approach compared to standard flow cells. The phenotype informative SNPs (piSNPs) and ancestry informative SNPs (aiSNPs) were thoroughly examined through sensitivity, reproducibility and repeatability, concordance, robustness (mock casework) and low level DNA mixture studies purposely selecting individuals with different phenotypes (hair and eye color) when possible and different biogeographical ancestry. SNP locus-specific interpretation thresholds were established for the Universal Analysis Software (UAS) based on surviving alleles and SNP predictor rank to minimize false homozygous genotypes and maximize the information that can be derived from an unknown sample. Dropin alleles' intensity determined an appropriate threshold to minimize false heterozygous SNP genotypes. The selection of inappropriate interpretation thresholds was shown to have major consequences on phenotypic predictions. A 3.2% and 4.8% minor DNA component contribution to a DNA mixture had no impact on ancestry predictions whereas a 9.1% contribution did. The multi-locus SNP genotypes generated using the ForenSeq™ DNA Signature Prep kit/Primer Mix B were shown to be reliable, reproducible, concordant and resulted in predictions that were also reliable, reproducible and concordant based on the limited number of donors (N = 19) used in this study.

Validation
ForenSeq™
Biogeographical ancestry predictions
Micro MiSeq® Flow Cells
Forensic DNA phenotyping
SNP-specific interpretation thresholds


Genome-wide association mapping of the architecture of susceptibility to the root-knot nematode Meloidogyne incognita in Arabidopsis thaliana.

Abstract: Susceptibility to the root-knot nematode Meloidogyne incognita in plants is thought to be a complex trait based on multiple genes involved in cell differentiation, growth and defence. Previous genetic analyses of susceptibility to M. incognita have mainly focused on segregating dominant resistance genes in crops. It is not known if plants harbour significant genetic variation in susceptibility to M. incognita independent of dominant resistance. To study the genetic architecture of susceptibility to M. incognita, we analysed nematode reproduction on a highly diverse set of 340 natural inbred lines of Arabidopsis thaliana with genome-wide association mapping. We observed a surprisingly large variation in nematode reproduction among these lines. Genome-wide association mapping revealed four quantitative trait loci (QTLs) located on chromosomes 1 and 5 of A. thaliana significantly associated with reproductive success of M. incognita, none of which harbours typical resistance gene homologues. Mutant analysis of three genes located in two QTLs showed that the transcription factor BRASSINAZOLE RESISTANT1 and an F-box family protein may function as (co-)regulators of susceptibility to M. incognita in Arabidopsis. Our data suggest that breeding for loss-of-susceptibility, based on allelic variants critically involved in nematode feeding, could be used to make crops more resilient to root-knot nematodes.

D018506:Gene Expression Regulation, Plant

D020022:Genetic Predisposition to Disease

genome-wide association
susceptibility
Meloidogyne incognita
Arabidopsis thaliana
F-box protein
allelic variation
brassinosteroid signalling


Effect of treatment with inhaled corticosteroid on serum periostin levels in asthma.

Abstract:
BACKGROUND AND OBJECTIVE
Periostin is a biomarker of eosinophilic airway inflammation and may contribute to airway remodeling in asthma. The anti-inflammatory activity of inhaled corticosteroids (ICS) for asthma control is widely recognized. The aim of this study was to assess the effects of ICS on serum periostin levels and its relationships to inflammation and airway geometry.

METHODS
Forty-two healthy controls and 20 patients with steroid-naïve asthma before and after treatment with fluticasone propionate (800 μg/day for 16 weeks) were examined. Serum periostin, lung function and inflammatory cell counts in sputum were measured. Airway dimensions were determined by quantitative computed tomography (total area of the airway (Ao), wall area (WA), wall thickness (T) and percentage wall area (WA%) ).

RESULTS
Serum periostin concentrations were significantly higher in patients with asthma than in controls. Periostin levels were correlated with airway wall thickness and sputum eosinophilia and inversely correlated with airflow limitation in asthma. ICS significantly decreased serum periostin (P < 0.01), decreased WA corrected for body surface area (WA/BSA, P < 0.05), T/√BSA (P < 0.01) and WA% (P < 0.01), reduced the percentage of sputum eosinophils (P < 0.01) and improved airflow limitation. The decrease in serum periostin levels was associated with an increased per cent predicted forced expiratory volume in 1 s (r = -0.64, P < 0.01), decreased WA/BSA (r = 0.46, P < 0.05) and decreased sputum eosinophils (r = 0.71, P < 0.01).

CONCLUSION
Serum periostin levels respond partially to ICS and may reflect a reduction in airway inflammation and wall thickening in asthma.

inhaled corticosteroid
periostin
asthma
inflammation
airway dimension


Inoculation of Lewis lung carcinoma cells enhances formalin-induced pain behavior and spinal Fos expression in mice.

Abstract: The incidence of lung cancer has rapidly increased and cancer patients at a later cancer stage frequently suffer from unbearable cancer-associated pain. However, the pathophysiology of lung cancer pain has not been fully described due to a lack of appropriate animal models. This study was designed to determine the effect of Lewis lung carcinoma (LLC) cell inoculation on formalin-induced pain behavior and spinal Fos expression in C57BL/6 mice. LLC cells (1.5 × 105, 2.5 × 105, 3.0 × 105 or 5.0 × 105) were inoculated into back or peri-sciatic nerve areas. Back area inoculation was adopted to determine the effect of cancer cell circulating factors and the peri-sciatic nerve area was used to evaluate the possible effects of cancer cell contacting and circulating factors on formalin-induced pain. At postinoculation day 7, LLC cell (5.0 × 105) inoculations in both back and peri-sciatic nerve area significantly increased formalin-induced paw-licking time and spinal Fos expression over those in cell-media-inoculated (control) mice. Enhanced pain behavior and spinal Fos expression were significantly suppressed by ibuprofen pretreatment (250 mg/kg). The results of this study suggest that LLC cell circulating factors and inflammatory responses may be critical in enhancing pain sensation in the early stage of lung cancer cell inoculation.

Choi|Jae-Gyun|JG|
Kim|Jae-Min|JM|
Kang|Dong-Wook|DW|
Choi|Jung-Wan|JW|
Park|Jin Bong|JB|
Ahn|Seong-Hun|SH|
Ryu|Yeonhee|Y|
Kim|Hyun-Woo|HW|

Lewis lung carcinoma
pain
Fos
formalin
lung neoplasms


"Girls Aren't Meant to Exercise": Perceived Influences on Physical Activity among Adolescent Girls-The HERizon Project.

Abstract:
BACKGROUND
Adolescent girls are less active than boys, with approximately 10% of girls in Ireland and the United Kingdom meeting the minimum recommended daily physical activity (PA) guidelines. This study investigated factors perceived to influence PA among adolescent girls from low socioeconomic areas in order to inform the design of a future intervention (The HERizon Project).

METHODS
A total of 48 adolescent girls (13-18 years) from low socioeconomic areas of the United Kingdom and Ireland participated in focus groups (n = 8), to explore perspectives of physical activity and the influence of gender within this. Focus groups were thematically analyzed and interpreted within a socioecological framework.

RESULTS
Most girls enjoyed PA and were aware of its benefits. They identified both barriers and facilitators to PA at intrapersonal (fear of judgement and changing priorities WITH age), interpersonal (changing social pressures and support from others) and organizational (delivery of PE) levels. Gender inequality was a multilevel factor, crossing all socioecological levels.

CONCLUSION
Although many adolescent girls enjoy PA, their experiences appear to be limited by a fear of judgement and an overarching sense of gender inequality. Future interventions, such as the HERizon Project, should address influences at intrapersonal, interpersonal and organizational levels to promote positive PA experiences for adolescent girls.

girls
exercise
physical activity
adolescence
focus groups
qualitative
socioecological model


Gaining insights in the nutritional metabolism of amphibians: analyzing body nutrient profiles of the African clawed frog, Xenopus laevis.

Abstract: Whole bodies of Xenopus laevis (n = 19) were analysed for chemical composition and morphometrics. The nutrient profile (macronutrients, amino acids, fatty acids and minerals) was evaluated by sex; interactions among variables with body weights and lengths, and comparisons made with different species of marine and fresh water fish. Significant differences were found in morphometric measurements, water content, several minerals and fatty acids between sexes of X. laevis. Amino acid profiles differed in methionine, proline and cysteine, which could underlie different metabolic pathways in frogs when compared to fish. In addition, fatty acid profiles revealed more monounsaturated and n - 6 polyunsaturated fatty acids in frogs than in fish, more similar to values reported for terrestrial than aquatic vertebrates. Important interactions were also found between body measurements and fat, calcium, and phosphorus, as well as between essential and non-essential amino acids. The results indicate that frogs might have particular biochemical pathways for several nutrients, dependent on sex and linked to body weight, which ultimately could reflect specific nutrient needs.

Brenes-Soto|Andrea|A|
Dierenfeld|Ellen S|ES|
Bosch|Guido|G|
Hendriks|Wouter H|WH|
Janssens|Geert P J|GPJ|

Nutrition
Metabolism
Xenopus laevis
Amino acids
Fatty acids
Body composition


ABAP1 Plays a Role in the Differentiation of Male and Female Gametes in Arabidopsis thaliana.

Abstract: The correct development of a diploid sporophyte body and a haploid gametophyte relies on a strict coordination between cell divisions in space and time. During plant reproduction, these divisions have to be temporally and spatially coordinated with cell differentiation processes, to ensure a successful fertilization. Armadillo BTB Arabidopsis protein 1 (ABAP1) is a plant exclusive protein that has been previously reported to control proliferative cell divisions during leaf growth in Arabidopsis. Here, we show that ABAP1 binds to different transcription factors that regulate male and female gametophyte differentiation, repressing their target genes expression. During male gametogenesis, the ABAP1-TCP16 complex represses CDT1b transcription, and consequently regulates microspore first asymmetric mitosis. In the female gametogenesis, the ABAP1-ADAP complex represses EDA24-like transcription, regulating polar nuclei fusion to form the central cell. Therefore, besides its function during vegetative development, this work shows that ABAP1 is also involved in differentiation processes during plant reproduction, by having a dual role in regulating both the first asymmetric cell division of male gametophyte and the cell differentiation (or cell fusion) of female gametophyte.

Cabral|Luiz M|LM|
Masuda|Hana P|HP|
Ballesteros|Helkin F|HF|
de Almeida-Engler|Janice|J|
Alves-Ferreira|Márcio|M|
De Toni|Karen L G|KLG|
Bizotto|Fernanda M|FM|
Ferreira|Paulo C G|PCG|
Hemerly|Adriana S|AS|

ABAP1
female gametophyte differentiation
ADAP
DNA replication
TCP
male gametophyte differentiation


Prospective comparison of capillary and venous brain biomarker S100B: capillary samples have large inter-sample variation and poor correlation with venous samples.

Abstract:
BACKGROUND
Guidelines for the emergency management of mild traumatic brain injury have been used for over a decade and are considered safe. However, they recommend computerized tomography for at least half of these patients. The Scandinavian Neurotrauma Committee guideline uses serum S100B protein level to rule out intracranial hemorrhage. Analysis of capillary serum S100B protein level has not yet been employed for this purpose. The primary aim of this study was to investigate the correlation and agreement of capillary and venous serum S100B protein level over a spectrum of concentrations typical for mild traumatic brain injury.

METHODS
Eighteen patients with traumatic intracranial hemorrhage and 39 volunteers without trauma to the head within the past 7 days were recruited. Blood was sampled from patients with intracranial hemorrhage daily up to four consecutive days and healthy volunteers were sampled once during the study. One venous and two capillary samples were drawn at each sampling event. Samples were analyzed using the Cobas e411 S100 electrochemiluminescence assay.

RESULTS
Median serum S100B protein level of capillary sampling 1 was 0.12 (IQR 0.075-0.21) μg/l and median serum S100B protein level of capillary sampling 2 was 0.13 (IQR 0.08-0.22) μg/l. Median serum S100B protein level of all venous samples was 0.05 (IQR 0.03-0.07) μg/l. Correlation plots of capillary and venous samples showed poor correlation and Bland-Altman plots showed a large dispersion of samples and wide limits of agreement.

CONCLUSION
The results of this study indicate that correlation and agreement between capillary and venous samples are low, and because of this, we cannot recommend studies on capillary serum S100B protein level to rule out intracranial hemorrhage in mild traumatic brain injury. Given the limitations of the current sampling and analysis methods of capillary protein S100B protein level, we conclude that evaluating its predictive ability to rule out intracranial hemorrhage should be withheld until more reliable methods can be incorporated into the study design.

S100 calcium-binding protein beta subunit


Cardiac mucosa at the gastro-oesophageal junction: indicator of gastro-oesophageal reflux disease? Data from a prospective central European multicentre study on histological and endoscopic diagnosis of oesophagitis (histoGERD trial).

Abstract:
AIMS
The origin and significance of cardiac mucosa at the gastro-oesophageal junction are controversial. In the prospective Central European multicentre histoGERD trial, we aimed to assess the prevalence of cardiac mucosa, characterized by the presence of glands composed of mucous cells without parietal cells, and to relate its presence to features related to gastro-oesophageal reflux disease (GORD).

METHODS AND RESULTS
One thousand and seventy-one individuals (576 females and 495 males; median age 53 years) were available for analysis. Overall, in biopsy specimens systematically taken from above and below the gastro-oesophageal junction, cardiac mucosa was observed in 713 (66.6%) individuals. Its presence was associated with patients' symptoms and/or complaints (P = 0.0025), histological changes of the squamous epithelium (P < 0.001) indicative of GORD, intestinal metaplasia (P < 0.001), and an endoscopic diagnosis of oesophagitis (P < 0.001). No association with an endoscopic diagnosis of Barrett's oesophagus or with gastric pathology, particularly Helicobacter infection, was observed.

CONCLUSIONS
Cardiac mucosa is a common finding in biopsy specimens taken from the gastro-oesophageal junction. Its association with reflux symptoms, histological changes indicating GORD and the endoscopic diagnosis of oesophagitis suggests that injury and repair related to GORD contribute to its development and/or expansion.

Langner|Cord|C|
Schneider|Nora I|NI|
Plieschnegger|Wolfgang|W|
Schmack|Bertram|B|
Bordel|Hartmut|H|
Höfler|Bernd|B|
Eherer|Andreas J|AJ|
Wolf|Eva-Maria|EM|
Rehak|Peter|P|
Vieth|Michael|M|

gastro-oesophageal junction
reflux disease
prevalence
metaplasia
gastric cardia


Genetic determinants of lipid-lowering response to atorvastatin therapy in an Indian population.

Abstract:
WHAT IS KNOWN AND OBJECTIVE
Statins form the backbone of lipid-lowering therapy for the prevention of cardiovascular disease. However, there is large interindividual variability in clinical response to statin treatment. Several gene variants that can be aligned to either the pharmacokinetics or pharmacodynamics of statin have been proposed as potentially important determinants of statin response. We aimed to study the association of known variations in SLCO1B1, CYP3A4, ABCB1, CYP3A5, ABCG5 and CYP7A1 genes with lipid levels in response to atorvastatin therapy.

METHODS
Genotypes were determined using multiplex allele-specific polymerase chain reaction in 177 Indian patients, treated with 10 mg of atorvastatin for 8 weeks. Low-density lipoprotein-cholesterol (LDL-C) levels were recorded at baseline and after 8 weeks of atorvastatin treatment.

RESULTS AND DISCUSSION
A total of 177 hypercholesterolaemic patients were genotyped to study genetic determinants of atorvastatin response. The genotype distribution for all polymorphisms investigated was in Hardy-Weinberg equilibrium. In our study, patients with wild-type genotypes of CYP7A1 (rs3808607), CYP3A4 (rs2740574), SLCO1B1 (rs2306283) and variant allele-carrying genotype of ABCB1 (rs2032582, rs1045642) showed significantly greater LDL-cholesterol reductions in response to atorvastatin therapy.

WHAT IS NEW AND CONCLUSION
The variable response to atorvastatin therapy in terms of LDL-cholesterol lowering due to genetic variations in CYP7A1, CYP3A4, SLCO1B1 and ABCB1 is a promising finding. Further validation in large Indian cohorts is required before it can be assessed for clinical utility.

Kadam|P|P|
Ashavaid|T F|TF|
Ponde|C K|CK|
Rajani|R M|RM|

atorvastatin
low-density lipoprotein-cholesterol
polymorphisms
pharmacogenetics


Reappraisal of Regional Growth Charts in the Era of WHO Growth Standards.

Abstract: After the WHO Growth Standards (WHOGS) was published in 2006, many countries in the world endorsed and adopted the new growth references as a standard measure for the growth of infants and young children. Certainly, the WHOGS has an impact on the global policy about obesity and underweight in children. Such WHOGS innovation has influenced many regional health authorities and academies, which have managed their own growth charts for a long time, in changing their strategies to develop and use regional growth charts. In Korea, along with the tradition to create a national growth chart every decade, we now face a new era of advancing with the WHOGS.

World Health Organization Growth Standards


Effects of renalase deficiency on liver fibrosis markers in a nonalcoholic steatohepatitis mouse model.

Abstract: Progression of nonalcoholic steatohepatitis (NASH) is attributed to several factors, including inflammation and oxidative stress. In recent years, renalase has been reported to suppress oxidative stress, apoptosis and inflammation. A number of studies have suggested that renalase may be associated with protecting the liver from injury. The present study aimed to clarify the effects of renalase knockout (KO) in mice with NASH that were induced with a choline‑deficient high‑fat diet (CDAHFD) supplemented with 0.1% methionine. Wild type (WT) and KO mice (6‑week‑old) were fed a normal diet (ND) or CDAHFD for 6 weeks, followed by analysis of the blood liver function markers and liver tissues. CDAHFD intake was revealed to increase blood hepatic function markers, lipid accumulation and oxidative stress compared with ND, but no significant differences were observed between the WT and KO mice. However, in the KO‑CDAHFD group, the Adgre1 and Tgfb1 mRNA levels were significantly higher, and α‑SMA expression was significantly lower compared with the WT‑CDAHFD group. Furthermore, the Gclc mRNA and phosphorylated protein kinase B (Akt) levels were significantly lower in the KO‑ND group compared with the WT‑ND group. The results of the current study indicated that as NASH progressed in the absence of renalase, oxidative stress, macrophage infiltration and TGF‑β expression were enhanced, while α‑SMA expression in NASH may be partly suppressed due to the decreased phosphorylation of Akt level.

Tokinoya|Katsuyuki|K| Sekine|Nanami|N| Aoki|Kai|K| Ono|Seiko|S| Kuji|Tomoaki|T| Sugasawa|Takehito|T| Yoshida|Yasuko|Y| Takekoshi|Kazuhiro|K|

D065626:Non-alcoholic Fatty Liver Disease

renalase
liver
oxidative stress
Akt
transforming growth factor‑β
α‑smooth muscle actin


External validation of a new classification of spinal lipomas based on embryonic stage.

Abstract:
OBJECTIVE
Contention exists regarding appropriate classification and management of spinal lipomas (SLs). Given the heterogeneity of SLs, omissions and overlap between surgically incomparable groups exist in conventional classification systems. The new classification of spinal lipoma (NCSL) recently proposed by Morota et al. delineates morphology by embryological pathogenesis and the resultant operative difficulty. Here, the authors aimed to validate the NCSL by applying it to patients who had been operated on at their institution.

METHODS
All children who had undergone resection for SL between 2014 and 2018 were included in this analysis. MRI studies were independently reviewed and classified by three adjudicators. Baseline characteristics, inter-adjudicator agreement, coexisting anomalies and/or malformations, and postoperative outcomes and complications were analyzed.

RESULTS
Thirty-six patients underwent surgical untethering for SL: NCSL type 1 in 5 patients (14%), type 2 in 14 patients (39%), type 3 in 4 patients (11%), and type 4 in 13 patients (36%). All classification was agreed on first assignment by the adjudicators. Radical or near-radical resection, which was attempted in all patients, was always possible in those with type 1 and 4 SL, but never in those with type 2 and 3 SL. Neurological stabilization and/or improvement were observed in all patients at the last follow-up.

CONCLUSIONS
The NCSL was found to be a logical and reproducible system to apply in this SL population. All cases were successfully classified with a high degree of inter-assessor agreement. Widespread establishment of a commonly adopted and clinically useful classification system will enable clinicians to improve patient selection as well as discussion with patient representatives during the decision-making process.

IOM = intraoperative neurophysiological monitoring

NCSL = new classification of spinal lipoma

VACTERL = vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, and limb abnormalities


Quassinoids from the Roots of Eurycoma longifolia and Their Anti-Proliferation Activities.

Abstract: A phytochemical investigation on the roots of medicinal plant Eurycoma longifolia resulted in the isolation of 10 new highly oxygenated C20 quassinoids longifolactones G‒P (1-10), along with four known ones (11-14). Their chemical structures and absolute configurations were unambiguously elucidated on the basis of comprehensive spectroscopic analysis and X-ray crystallographic data. Notably, compound 1 is a rare pentacyclic C20 quassinoid featuring a densely functionalized 2,5-dioxatricyclo[5.2.2.04,8]undecane core. Compound 4 represents the first example of quassinoids containing a 14,15-epoxy functionality, and 7 features an unusual α-oriented hydroxyl group at C-14. All isolated compounds were evaluated for their anti-proliferation activities on human leukemia cells. Among the isolates, compounds 5, 12, 13, and 14 potently inhibited the in vitro proliferation of K562 and HL-60 cells with IC50 values ranging from 2.90 to 8.20 μM.

Yang|Wei-Qun|WQ| Tang|Wei|W| Huang|Xiao-Jun|XJ| Song|Jian-Guo|JG|0000-0003-3843-355X Li|Yue-Yue|YY| Xiong|Yu|Y| Fan|Chun-Lin|CL| Wu|Zhen-Long|ZL| Wang|Ying|Y|0000-0003-4524-1812 Ye|Wen-Cai|WC|

quassinoids
Eurycoma longifolia
anti-proliferation activities
Simaroubaceae
natural products


Developments in bioprocess for bacterial cellulose production.

Abstract: Bacterial cellulose (BC) represents a novel bio-origin nonomaterial with its unique properties having diverse applications. Increased market demand and low yield are the major reason for its higher cost. Bacteria belonging to Komagataeibacter sp are the most exploited ones for BC production. Development of a cost-effective bioprocess for higher BC production is desirable. Though static fermentation modes have been majorly employed for BC production using tray fermenters, agitated mode has also been employed successfully with air-lift fermenters as well as stirred tank reactors. Bioprocess advances in recent years has led BC production to an upper level; however, challenges of aeration requirement and labor cost towards the higher end is associated with static cultivation at large scale. We have discussed the bioprocess development for BC production in recent years along with the challenges associated and the path forward.

Singhania|Reeta Rani|RR|
Patel|Anil Kumar|AK|
Tseng|Yi-Sheng|YS|
Kumar|Vinod|V|
Chen|Chiu-Wen|CW|
Haldar|Dibyajyoti|D|
Saini|Jitendra Kumar|JK|
Dong|Cheng-Di|CD|

Bioprocess
Bacterial cellulose
Komagataeibacter
Bioreactor
Nanocellulose


Aging exacerbates obesity-induced oxidative stress and inflammation in perivascular adipose tissue in mice: a paracrine mechanism contributing to vascular redox dysregulation and inflammation.

Abstract: Obesity in the elderly individuals is increasing at alarming rates and there is evidence suggesting that elderly individuals are more vulnerable to the deleterious cardiovascular effects of obesity than younger individuals. However, the specific mechanisms through which aging and obesity interact to promote the development of cardiovascular disease remain unclear. The present study was designed to test the hypothesis that aging exacerbates obesity-induced inflammation in perivascular adipose tissue, which contributes to increased vascular oxidative stress and inflammation in a paracrine manner. To test this hypothesis, we assessed changes in the secretome, reactive oxygen species production, and macrophage infiltration in periaortic adipose tissue of young (7 month old) and aged (24 month old) high-fat diet-fed obese C57BL/6 mice. High-fat diet-induced vascular reactive oxygen species generation significantly increased in aged mice, which was associated with exacerbation of endothelial dysfunction and vascular inflammation. In young animals, high-fat diet-induced obesity promoted oxidative stress in the perivascular adipose tissue, which was associated with a marked proinflammatory shift in the profile of secreted cytokines and chemokines. Aging exacerbated obesity-induced oxidative stress and inflammation and significantly increased macrophage infiltration in periaortic adipose tissue. Using cultured arteries isolated from young control mice, we found that inflammatory factors secreted from the perivascular fat tissue of obese aged mice promote significant prooxidative and proinflammatory phenotypic alterations in the vascular wall, mimicking the aging phenotype. Overall, our findings support an important role for localized perivascular adipose tissue inflammation in exacerbation of vascular oxidative stress and inflammation in aging, an effect that likely enhances the risk for development of cardiovascular diseases from obesity in the elderly individuals.

Bailey-Downs|Lora C|LC|
Tucsek|Zsuzsanna|Z|
Toth|Peter|P|
Sosnowska|Danuta|D|
Gautam|Tripti|T|
Sonntag|William E|WE|
Csiszar|Anna|A|
Ungvari|Zoltan|Z|

Adiposity
Obesity
Fat
Diabetes
Metabolic disease


The Sight Loss and Vision Priority Setting Partnership (SLV-PSP): overview and results of the research prioritisation survey process.

Abstract:
OBJECTIVES
The Sight Loss and Vision Priority Setting Partnership aimed to identify research priorities relating to sight loss and vision through consultation with patients, carers and clinicians. These priorities can be used to inform funding bodies' decisions and enhance the case for additional research funding.

DESIGN
Prospective survey with support from the James Lind Alliance.

SETTING
UK-wide National Health Service (NHS) and non-NHS.

PARTICIPANTS
Patients, carers and eye health professionals. Academic researchers were excluded solely from the prioritisation process. The survey was disseminated by patient groups, professional bodies, at conferences and through the media, and was available for completion online, by phone, by post and by alternative formats (Braille and audio).

OUTCOME MEASURE
People were asked to submit the questions about prevention, diagnosis and treatment of sight loss and eye conditions that they most wanted to see answered by research. Returned survey questions were reviewed by a data assessment group. Priorities were established across eye disease categories at final workshops.

RESULTS
2220 people responded generating 4461 submissions. Sixty-five per cent of respondents had sight loss and/or an eye condition. Following initial data analysis, 686 submissions remained which were circulated for interim prioritisation (excluding cataract and ocular cancer questions) to 446 patients/carers and 218 professionals. The remaining 346 questions were discussed at final prioritisation workshops to reach agreement of top questions per category.

CONCLUSIONS
The exercise engaged a diverse community of stakeholders generating a wide range of conditions and research questions. Top priority questions were established across 12 eye disease categories.

Rowe|Fiona|F| Wormald|Richard|R| Cable|Richard|R| Acton|Michele|M| Bonstein|Karen|K| Bowen|Michael|M| Bronze|Carol|C| Bunce|Catey|C| Conroy|Dolores|D| Cowan|Katherine|K| Evans|Kathy|K| Fenton|Mark|M| Giles|Heather|H| Gordon|Iris|I| Halfhide|Louise|L| Harper|Robert|R| Lightstone|Anita|A| Votruba|Marcela|M| Waterman|Heather|H| Zekite|Antra|A|

Sight loss
Vision
Priorities
Partnership
Research
James Lind Alliance


rBC2LCN lectin as a potential probe of early-stage HER2-positive breast carcinoma.

Abstract: The recombinant N-terminal domain of BC2L-C lectin (rBC2LCN) is useful for detecting not only human pluripotent stem cells but also some cancers. However, the cancer types and stages that can be detected by rBC2LCN remain unclear. In this study, we identified the human breast carcinoma subtypes and stages that can be detected by rBC2LCN. Compared with rBC2LCN-negative breast carcinoma cell lines, the rBC2LCN-positive cells expressed higher levels of human epidermal growth factor receptor 2 (HER2) and epithelial marker genes. Importantly, rBC2LCN histochemical staining of human breast carcinoma tissues demonstrated the utility of rBC2LCN in detecting breast carcinoma types that express HER2 and have not spread much in the early phase of growth. We conclude that rBC2LCN may have potential as a detection probe and a drug delivery vehicle to identify and treat early-stage HER2-positive breast carcinoma.

Mawaribuchi|Shuuji|S| Haramoto|Yoshikazu|Y| Tateno|Hiroaki|H| Onuma|Yasuko|Y| Aiki|Yasuhiko|Y| Ito|Yuzuru|Y|0000-0001-7923-865X

D000970:Antineoplastic Agents
D001426:Bacterial Proteins
D001940:Breast
D001943:Breast Neoplasms
D057508:Burkholderia cenocepacia
D004337:Drug Carriers
D005240:Feasibility Studies
D005260:Female
D006801:Humans
D037102:Lectins
D061986:MCF-7 Cells
D015335:Molecular Probes
D009367:Neoplasm Staging
D018719:Receptor, ErbB-2
D011994:Recombinant Proteins
D046888:Tissue Array Analysis


The evolution of offensive realism.

Abstract: Offensive realism, a theory of international relations, holds that states are disposed to competition and conflict because they are self-interested, power maximizing, and fearful of other states. Moreover, it argues that states are obliged to behave this way because doing so favors survival in the international system. Debate continues as to whether modern states actually do, or should, behave in this way, but we are struck by a different question. In this article, we ask whether the three core assumptions about behavior in offensive realism-self-help, power maximization, and outgroup fear-have any basis in scientific knowledge about human behavioral evolution. We find that these precise traits are not only evolutionarily adaptive but also empirically common across the animal kingdom, especially in primate and human societies. Based on these findings, we hypothesize that states behave as offensive realists predict not just because of anarchy in the modern international system but also because of the legacy of our evolution. In short, offensive realism may really be describing the nature of the human species more than the nature of the international system. If our hypothesis is correct, then evolutionary theory offers the following: (1) a novel ultimate cause of offensive realist behavior; (2) an extension of offensive realism to any domain in which humans compete for power; and (3) an explanation for why individual leaders themselves, and not just states, seek power. However, a key insight from evolution is that the primacy of self-help, power maximization, and outgroup fear does not necessarily condemn individuals or groups to competition and conflict; rather, these traits can in themselves give rise to cooperation and alliances.

Johnson|Dominic D P|DD|
Phil|D|D|
Thayer|Bradley A|BA|

evolution
offensive realism
human behavior
Anarchy
causes of war
classical realism
international relations theory
international security


Reduction of traditional food consumption in Brazilian diet: trends and forecasting of bean consumption (2007-2030).

Abstract:
OBJECTIVE
To identify changes in traditional dietary behaviour through the evaluation of trends in bean consumption among adults in Brazil between 2007 and 2017 and to estimate its projections up to 2030.

DESIGN
Time-series analysis conducted with data from the Surveillance System for Protective and Risk Factors for Chronic Diseases by Telephone Survey (Vigitel) between 2007 and 2017. Weekly consumption of beans was analysed. Prais-Winsten regression evaluated trends for the entire period of study (2007-2017) and in two periods of analyses (2007-2011 and 2012-2017) for the complete set of the population and stratified by socio-demographic characteristics. Estimated prevalence projections were calculated up to the year 2030 using its tendency from 2012 to 2017.

SETTING
Brazil.

PARTICIPANTS
A probabilistic sample of 572 675 Brazilian adults aged ≥ 18 years.

RESULTS
Changes in traditional dietary pattern were identified. Regular consumption of beans (≥ 5 d/week) presented a stable prevalence trend for the total population in the complete and the first analysed period, but a significant decrease in the second half (67·5 % to 59·5 %) among both genders, all age groups and educational levels (except for ≥12 years). The higher magnitude of regular consumption of beans will occur up to the year of 2025 for the total population (46·9 %), when it will be less frequent in the week.

CONCLUSION
Reductions in the weekly consumption of beans may represent the weakness of a traditional food culture in a globalised food system. By 2025, regular consumption of beans will cease to be the predominant habit in the country.

Food consumption
Dietary pattern
Nutrition
Public health
Unprocessed food


Conservative management of bilateral traumatic testicular dislocation in a 10-year-old boy.

Abstract: A 10-year-old boy fell from a one-meter-high Jacuzzi ladder in a hot spring facility, landing in a straddle position, and injured his perineum. He visited the emergency room of our hospital immediately after the injury. Magnetic resonance imaging (MRI) revealed a tear of the corpus spongiosum urethra, and compression due to a hematoma. With the hematoma spreading to the scrotum, the testes became inverted and dislocated to the inguinal region on both sides. Without surgery or interventions, the testes descended into the scrotum on the third day after the injury before fibrillation and scarring began. Testicular dislocation by injury is rare and encountered exclusively in children. It is generally treated with surgery to retain testicular function. We selected conservative management, as our patient had a closed injury without testicular torsion, and the testicular dislocation was associated with compression by hematoma, which could possibly recover with regression of the hematoma.

Shirono|Yuko|Y| Yamaguchi|Shunsuke|S| Takahashi|Eisuke|E| Terunuma|Masahiro|M|

conservative management
testicular dislocation
inguinal dislocation
pediatric patient
straddle injury


Malignant triton tumor below the peritoneal reflection: a case report.

Abstract: Malignant triton tumor (MTT) is a rare subtype of malignant peripheral nerve sheath tumors (MPNSTs) histologically defined by rhabdomyoblastic differentiation. MTTs are primarily found in the head, neck, extremities and trunk, but rare cases of MTT within the buttock, the mediastinum and the retroperitoneum have also been documented. We present the case of a 47-year-old male patient who initially presented with right flank pain and hematuria in July 2019, who was found to have a large pelvic mass below peritoneal reflection. Complete resection of the mass was performed, and pathology identified the mass as a MTT.

Seddighzadeh|Rachael Price|RP|
Brower|Steven|S|
Tzeng|Jausheng|J|
Serur|Anna|A|

malignant triton tumor
malignant peripheral nerve sheath tumor
colorectal surgery


Single dose darbepoetin alfa is useful in reducing red cell transfusions in leukemic children receiving chemotherapy.

Abstract: The role of erythropoiesis-stimulating agents (ESAs) in the management of chemotherapy-induced anemia (CIA) is becoming increasingly recognized in the field of medical oncology, with paucity of data in pediatrics. We evaluated the efficacy and tolerability of a single-dose darbepoetin alfa, a long-acting ESA, given to 35 pediatric acute lymphoblastic leukemia (ALL) children during induction chemotherapy. Compared to a retrospective control group, the studied patients have required significantly less units of packed red blood cells (0.88 units/patient in the studied group versus 2.04 units in controls), with no major side effects. We recommend further prospective double-blinded studies with more tailored dosing regimens in pediatric ALL cases and solid tumors.

Zachariah|Mathew|M| Elshinawy|Mohamed|M| Alrawas|Abdulhakim|A| Bashir|Wafa|W| Elbeshlawi|Ismail|I| Tony|Surekha|S| Wali|Yasser|Y|

D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma

darbepoetin alfa
chemotherapy
anemia
leukemia


An Update on the Synthesis of Pyrrolo[1,4]benzodiazepines.

Abstract: Pyrrolo[1,4]benzodiazepines are tricyclic compounds that are considered "privileged structures" since they possess a wide range of biological activities. The first encounter with these molecules was the isolation of anthramycin from cultures of Streptomyces, followed by determination of the X-ray crystal structure of the molecule and a study of its interaction with DNA. This opened up an intensive synthetic and biological study of the pyrrolo[2,1-c][1,4]benzodiazepines that has culminated in the development of the dimer SJG-136, at present in Phase II clinical trials. The synthetic efforts have brought to light some new synthetic methodology, while the contemporary work is focused on building trimeric pyrrolo[2,1-c][1,4]benzodiazepines linked together by various heterocyclic and aliphatic chains. It is the broad spectrum of biological activities of pyrrolo[1,2-a][1,4]benzodiazepines that has maintained the interest of researchers to date whereas several derivatives of the even less studied pyrrolo[1,2-d][1,4]benzodiazepines were found to be potent non-nucleoside HIV-1 reverse transcriptase inhibitors. The present review is an update on the synthesis of pyrrolo[2,1-c][1,4]benzodiazepines since the last major review of 2011, while the overview of the synthesis of the other two tricyclic isomers is comprehensive.

heterocycles
DNA-interactive agents
anti-HIV activity
anticancer activity
pyrrolobenzodiazepines
small molecules


Exploring the bark thickness-stem diameter relationship: clues from lianas, successive cambia, monocots and gymnosperms.

Abstract: Bark thickness is ecologically crucial, affecting functions from fire protection to photosynthesis. Bark thickness scales predictably with stem diameter, but there is little consensus on whether this scaling is a passive consequence of growth or an important adaptive phenomenon requiring explanation. With a comparative study across 913 species, we test the expectation that, if bark thickness-stem diameter scaling is adaptive, it should be possible to find ecological situations in which scaling is predictably altered, in this case between species with different types and deployments of phloem. 'Dicots' with successive cambia and monocots, which have phloem-free bark, had predictably thinner inner (mostly living) bark than plants with single cambia. Lianas, which supply large leaf areas with limited stem area, had much thicker inner bark than self-supporting plants. Gymnosperms had thicker outer bark than angiosperms. Inner bark probably scales with plant metabolic demands, for example with leaf area. Outer bark scales with stem diameter less predictably, probably reflecting diverse adaptive factors; for example, it tends to be thicker in fire-prone species and very thin when bark photosynthesis is favored. Predictable bark thickness-stem diameter scaling across plants with different photosynthate translocation demands and modes strongly supports the idea that this relationship is functionally important and adaptively significant.

lianas
bark thickness
adaptation
phloem
inner bark
outer bark
fire ecology
metabolic scaling


Interferon-I: The Pièce de Résistance of HIV-1 Transmission?

Abstract: Despite the extensive viral quasispecies that develops in an individual during the course of HIV-1 infection, transmission is typically established by a single donor viral variant. Recent studies now provide insight into the phenotypic properties influencing this selection process at transmission, including the contribution of resistance to type I interferons.

Tully|Damien C|DC|
Claiborne|Daniel T|DT|
Allen|Todd M|TM|

Transmission Resistance Interferon Bottleneck HIV Mucosal


Managing the front-line treatment for diffuse large B cell lymphoma and high-grade B cell lymphoma during the COVID-19 outbreak.

Abstract: The COVID-19 pandemic has dramatically challenged care for cancer patients, especially those with active treatment who represent a vulnerable population for SARS-CoV-2 infection. Aggressive lymphoid neoplasms, such as diffuse large B cell lymphoma and high-grade B cell lymphoma, need to be treated without delay in order to get the best disease outcome. Because of that, our clinical practice was changed to minimise the risk of SARS-CoV-2 infection while continuing haematological treatment. In this report, we analyse the management of front-line therapy in 18 patients during the COVID-19 outbreak, as well as the results of the implemented measures in their outcome.

D000971:Antineoplastic Combined Chemotherapy Protocols


Neuropsychiatric systemic lupus erythematosus is associated with a distinct type and shape of cerebral white matter hyperintensities.

Abstract:
OBJECTIVES
Advanced white matter hyperintensity (WMH) markers on brain MRI may help reveal underlying mechanisms and aid in the diagnosis of different phenotypes of systemic lupus erythematosus (SLE) patients experiencing neuropsychiatric (NP) manifestations.

METHODS
In this prospective cohort study we included a clinically well-defined cohort of 155 patients consisting of 38 patients with NPSLE (26 inflammatory and 12 ischaemic phenotype) and 117 non-NPSLE patients. Differences in 3 T MRI WMH markers (volume, type and shape) were compared between patients with NPSLE and non-NPSLE and between patients with inflammatory and ischaemic NPSLE by linear and logistic regression analyses corrected for age, sex and intracranial volume.

RESULTS
Compared with non-NPSLE (92% female; mean age 42 ± 13 years), patients with NPSLE (87% female; mean age 40 ± 14 years) showed a higher total WMH volume (B (95%-CI)): 0.46 (0.0 7 ↔0.86); p= 0.021), a higher periventricular/confluent WMH volume (0.46 (0.0 6 ↔0.86); p= 0.024), a higher occurrence of periventricular with deep WMH type (0.32 (0.1 3 ↔0.77); p= 0.011), a higher number of deep WMH lesions (3.06 (1.2 1 ↔4.90); p= 0.001) and a more complex WMH shape (convexity: -0.07 (-0.12↔-0.02); p= 0.011, concavity index: 0.05 (0.0 1 ↔0.08); p= 0.007). WMH shape was more complex in inflammatory NPSLE patients (89% female; mean age 39 ± 15 years) compared with patients with the ischaemic phenotype (83% female; mean age 41 ± 11 years) (concavity index: 0.08 (0.0 1 ↔0.15); p= 0.034).

CONCLUSION
We demonstrated that patients with NPSLE showed a higher periventricular/confluent WMH volume and more complex shape of WMH compared with non-NPSLE patients. This finding was particularly significant in inflammatory NPLSE patients, suggesting different or more severe underlying pathophysiological abnormalities.

Inglese|Francesca|F|0000-0003-4569-4272
Jaarsma-Coes|Myriam G|MG|
Steup-Beekman|Gerda M|GM|
Monahan|Rory|R|
Huizinga|Tom|T|
van Buchem|Mark A|MA|
Ronen|Itamar|I|
de Bresser|Jeroen|J|

Systemic
Lupus Erythematosus
White Matter Hyperintensity
Brain
Magnetic Resonance Imaging


Effect of taping on foot kinematics in persons with chronic ankle instability.

Abstract:
OBJECTIVES
To investigate differences in rigid-foot and multi-segmental foot kinematics between healthy (control) and chronic ankle instability (CAI) participants during running and to evaluate the effect of low-Dye (LD) and high-Dye (HD) taping on foot kinematics of CAI subjects.

DESIGN
Cross-sectional, comparative study.

METHODS
Kinematic data of 12 controls and 15 CAI participants were collected by a 3D motion analysis system during running. CAI participants performed barefoot (CAI_BF) running trials as well as trials with taping. A rigid Plug-in gait Model and the Rizzoli 3D Multi-Segment Foot Model were used. Groups were compared using one-dimensional statistical parametric mapping.

RESULTS
An increased inversion, a decreased dorsiflexion between the foot and tibia and a decreased external foot progression angle were found during terminal swing and early stance in the CAI_BF group. With respect to the taped conditions, post-hoc SPM{t} calculations highlighted a more dorsiflexed rearfoot (38-46% running cycle) in the CAI_HD compared to the CAI_LD, and a more inverted Mid-Met angle (6-24% running cycle) in the CAI_LD compared to the CAI_BF condition.

CONCLUSIONS
This study revealed significant differences in rigid foot and multi-segmental foot kinematics between all groups. As high-dye taping embraces shank-rearfoot and forefoot, it seems to have better therapeutic features with respect to low-dye taping as the latter created a more inverted forefoot which may not be recommended in this population.

Deschamps|Kevin|K|
Dingenen|Bart|B|
Pans|Femke|F|
Van Bavel|Isabelle|I|
Matricali|Giovanni Arnoldo|GA|
Staes|Filip|F|

Taping
Foot
Chronic ankle instability
Running
Multi-segment kinematics


Fast pulsatile blood flow measurement in deep tissue through a multimode detection fiber.

Abstract:
SIGNIFICANCE
Noninvasive in vivo fast pulsatile blood flow measurement in deep tissue is important because the blood flow waveform is correlated with physiological parameters, such as blood pressure and elasticity of blood vessels. Compromised blood flow may cause diseases, such as stroke, foot ulcer, and myocardial ischemia. There is great clinical demand for a portable and cost-effective device for noninvasive pulsatile blood flow measurement.

AIM
A diffuse-optics-based method, diffuse speckle pulsatile flowmetry (DSPF), was developed for fast measurement (∼300  Hz) of deep tissue blood flow noninvasively. To validate its performance, both a phantom experiment and in vivo demonstration were conducted.

APPROACH
Over the past two decades, single-mode fibers have been used as detection fibers in most diffuse-optics-based deep tissue blood flow measurement modalities. We used a multimode (MM) detection fiber with a core size of 200  μm for diffused speckle pattern detection. A background intensity correction algorithm was implemented for speckle contrast calculation. The MM detection fiber helped to achieve a level of deep tissue blood flow measurement similar to that of conventional modalities, such as diffuse correlation spectroscopy and diffuse speckle contrast analysis, but it increases the measurement rate of blood flow to 300 Hz.

RESULTS
The design and implementation of the DSPF system were introduced. The theory of the background intensity correction for the diffused speckle pattern detected by the MM fiber was explained. A flow phantom was built for validation of the performance of the DSPF system. An in vivo cuff-induced occlusion experiment was performed to demonstrate the capability of the proposed DSPF system.

CONCLUSIONS
An MM detection fiber can help to achieve fast (∼300  Hz) pulsatile blood flow measurement in the proposed DSPF method. The cost-effective device and the fiber-based flexible probe increase the usability of the DSPF system significantly.

Bi|Renzhe|R|
Du|Yao|Y|
Singh|Gurpreet|G|
Ho|Chris Jun-Hui|CJ|
Zhang|Shuyan|S|
Attia|Amalina Binte Ebrahim|ABE|
Li|Xiuting|X|
Olivo|Malini|M|

deep tissue blood flow
diffuse correlation spectroscopy
diffuse speckle contrast analysis
laser speckle


Segmentation guided registration of wide field-of-view retinal optical coherence tomography volumes.

Abstract: Patient motion artifacts are often visible in densely sampled or large wide field-of-view (FOV) retinal optical coherence tomography (OCT) volumes. A popular strategy for reducing motion artifacts is to capture two orthogonally oriented volumetric scans. However, due to larger volume sizes, longer acquisition times, and corresponding larger motion artifacts, the registration of wide FOV scans remains a challenging problem. In particular, gaps in data acquisition due to eye motion, such as saccades, can be significant and their modeling becomes critical for successful registration. In this article, we develop a complete computational pipeline for the automatic motion correction and accurate registration of wide FOV orthogonally scanned OCT images of the human retina. The proposed framework utilizes the retinal boundary segmentation as a guide for registration and requires only a minimal transformation of the acquired data to produce a successful registration. It includes saccade detection and correction, a custom version of the optical flow algorithm for dense lateral registration and a linear optimization approach for axial registration. Utilizing a wide FOV swept source OCT system, we acquired retinal volumes of 12 subjects and we provide qualitative and quantitative experimental results to validate the state-of-the-art effectiveness of the proposed technique. The source code corresponding to the proposed algorithm is available online.

Lezama|José|J|
Mukherjee|Dibyendu|D|
McNabb|Ryan P|RP|
Sapiro|Guillermo|G|
Kuo|Anthony N|AN|
Farsiu|Sina|S|

(100.2980) Image enhancement
(170.4470) Ophthalmology
(170.4500) Optical coherence tomography


Determination of human γδ T cell-mediated cytotoxicity using a non-radioactive assay system.

Abstract: The adoptive transfer of immune effector cells, such as CD8+ killer αβ T cells, γδ T cells, NK (natural killer) cells, and genetically-modified T cells, has been receiving increasing attention. It is essential to determine cellular cytotoxicity so as to monitor the function and quality of ex vivo-expanded immune effector cells before infusion. The most common method is the [51Cr]-sodium chromate release assay. It is, however, preferable to avoid the use of radioactive materials in clinical laboratories. In order to establish a non-radioactive alternative to the standard radioactive assay, we previously synthesized a chelate-forming prodrug (BM-HT) and demonstrated that a combination of BM-HT and europium (Eu3+) was useful to determine NK cell-mediated cytotoxicity. In the present study, we examined whether or not this improved assay system could be used to determine the cellular cytotoxicity exhibited by Vγ2Vδ2+ γδ T cells. In addition, we compared Eu3+ and terbium (Tb3+) in the measurement of cellular cytotoxicity. Our assay system using BM-HT could be used successfully for the analysis of both γδ T cell receptor (TCR)- and CD16-mediated cytotoxicity. When the intensity of fluorescence was compared between Eu3+ and Tb3+, Tb3+ chelate was more sensitive than Eu3+ chelate, suggesting that the detection system using Tb3+ is superior to Eu3+ when tumor cells are not efficiently labeled with BM-HT. The method established herein is expected to promote the development of novel adoptive cell therapies for cancer.

Tagod|Mohammed S O|MSO|
Mizuta|Satoshi|S|
Sakai|Yuki|Y|
Iwasaki|Masashi|M|
Shiraishi|Kengo|K|
Senju|Hiroaki|H|
Mukae|Hiroshi|H|
Morita|Craig T|CT|
Tanaka|Yoshimasa|Y|

D016692:Receptors, Antigen, T-Cell, gamma-delta

Non-radioactive cellular cytotoxicity assay


COVID-19 Pandemic-Knowledge, Attitudes, Behaviours, and Actions among Faculty of Health Sciences Students.

Abstract:
The aim of the study was to assess the level of knowledge about COVID-19 disease and preventive behaviour of undergraduate students of nursing, midwifery, and emergency medicine.

MATERIAL AND METHODS
An electronic survey was conducted among students of nursing, midwifery, and emergency medicine during the COVID-19 pandemic, from 8 April 2021 to 6 June 2021 in the Pomeranian Voivodeship.

RESULTS
A total of 37 men and 238 women participated in the study. A moderate level of knowledge was found in 88% and high in 11% of students Midwifery students had a higher level than nursing students (p = 0.002) and students of emergency medicine (p = 0.003). The female gender is much more afraid of SARS-CoV-2 virus infection (p = 0.021). The most common preventive measure was to avoid people who coughed or had a cold (93%). Only 84% of students were vaccinated. Students who had a high level of knowledge more often avoided people who coughed or had a cold (p = 0.03) and gave up on meeting with friends (p = 0.02).

CONCLUSIONS
Constant education of students on the principles of dealing with the risk of infection with SARS-CoV-2 is necessary. It is important to continually motivate students to adhere to the principles of prevention. In the face of the existing epidemiological threat, there is a need to change the curricula for the fields of health sciences by adding the subject infectious diseases-clinic and nursing, with special attention to practical aspects.

COVID-19 attitudes behaviours students knowledge


Multi-Patient Rabies Exposure on a Colorado River Rafting Expedition: Urgent vs. Emergent Transport Decision Making in an Austere Setting.

Abstract: We present a case of rabies exposure on a private river rafting trip on Grand Canyon National Park's Colorado River. Five individuals were exposed to an erratically acting bat; one of the individuals sustained a direct bite to the upper lip while sleeping. This case illustrates the challenges of austere medical care and evacuation in remote conditions while highlighting the importance of risk mitigation considerations in all austere situations.

Pearce|Emily A|EA|0000-0002-1766-1193
Farney|Aaron N|AN|
Banks|Laura|L|
Harrell|Andrew J|AJ|

Rabies
emergencies
ambulances
prevention & control


Founding pioneers of IVF update: Innovative researchers generating livebirths by 1982.

Abstract: This commentary adds accuracy and interesting information to the story of the founding pioneers of IVF which was published in this journal in 2018, at the 40th anniversary of the first IVF livebirth, namely Louise Joy Brown born 25 July 1978. Table 1 in that first publication is now updated to reflect extended information about Team 1 comprising the acknowledged "Fathers of IVF", but whose work is better tabulated as Team 1a from the NHS days in Oldham; and Team 1b covering the new period of private practice at Bourn Hall in Cambridge. With the passing of pioneer Ian Craft, co-author of the first article, further information came to light at his memorial service. There has now been some adjustment to the last few months of 1982, with correct inclusion of Israel into the list along with an interesting exposé of the two major pioneer facilities of that country. The previously cited third Australian groups (Team 12) have now been appropriately relegated to 1983, a year which experienced a plethora of IVF facilities around the world and the beginning of the IVF population boom.

Assisted reproductive technology (ART)
Fathers of IVF (updated)
First IVF infants
First IVF teams (updated)
Founding pioneers (updated)
IVF history


Ultrasound-guided injection of intralesional steroids in acute hidradenitis suppurativa lesions: A prospective study.

Abstract: The management of hidradenitis suppurativa (HS) flares with intralesional steroids lacks strong scientific evidence but limited data suggest that it may be useful. The objective of this study is to assess the clinical and ultrasound responses of HS flares to ultrasound-guided injections of intralesional triamcinolone (40 mg/ml) with a dilution 1:4 versus 1:2 at 30-day (t1), 60-day (t2), and 90-day (t3) follow-up. We recruited patients with ≤3 acute lesions, unresponsive to topical therapy. At baseline we assessed lesions clinically and by ultra-high frequency ultrasound (48 or 70 MHz) and randomly performed an ultrasound-guided injection of triamcinolone. Assessments were repeated at t1, t2, and t3 follow-up, re-injecting the lesion in the case of no or partial response. We treated 49 lesions: 38.8% showed improvements at t1; 46.9% at t2; 6% at t3; and 8.3% showed no clinical and ultrasound improvements. Long-term follow-up data confirmed a statistically significant reduction in Visual Analogue Scale (VAS)-pain, Dermatology Life Quality Index (DLQI), and HS-Physician Global Assessment (HS-PGA), as well as edema and vascular signals. No adverse effects were reported. Our study suggests that ultrasound-injections with a 1:2 dilution are beneficial for HS flares that do not respond to topical treatment and should be included in the therapeutic algorithm.

Iannone|Michela|M|0000-0002-1463-0017
Janowska|Agata|A|0000-0002-2271-3859
Oranges|Teresa|T|0000-0002-7277-3278
Balderi|Lorenzo|L|
Benincasa|Bianca Benedetta|BB|
Vitali|Saverio|S|
Tonini|Giulia|G|
Morganti|Riccardo|R|
Romanelli|Marco|M|
Dini|Valentina|V|

D017497:Hidradenitis Suppurativa
D006801:Humans
D015552:Injections, Intralesional
D011446:Prospective Studies
D012720:Severity of Illness Index
D014221:Triamcinolone
D018084:Ultrasonography, Interventional

intralesional steroids
hidradenitis suppurativa
HS flares
acute flare management
ultrasound guided injections


Pediatric cerebral aneurysms.

Abstract: Childhood intracranial aneurysms differ from those in the adult population in incidence and gender prevalence, cause, location, and clinical presentation. Endovascular treatment of pediatric aneurysms is the suggested approach because it offers both reconstructive and deconstructive techniques and a better clinical outcome compared with surgery; however, the long-term durability of endovascular treatment is still questionable, therefore long-term clinical and imaging follow-up is necessary. The clinical presentation, diagnosis, and treatment of intracranial aneurysms in children are discussed, and data from endovascular treatments are presented.

Gemmete|Joseph J|JJ|
Toma|Ahmed K|AK|
Davagnanam|Indran|I|
Robertson|Fergus|F|
Brew|Stefan|S|

D002533:Cerebral Angiography
D002548:Cerebral Revascularization
D002648:Child
D057510:Endovascular Procedures
D006801:Humans
D002532:Intracranial Aneurysm
D025321:Surgery, Computer-Assisted

Endovascular treatment
Pediatric aneurysm
Intracranial cerebral aneurysm
SAH