Herpes zoster might be an indicator for latent COVID 19 infection.

Abstract: Various cutaneous manifestations have been observed in patients with COVID-19 infection. Herpes zoster is a viral skin disease caused by varicella zoster that remains dormant in the dorsal root ganglia of cutaneous nerves following a primary chicken pox infection. In this report, we describe two cases COVID infection who first presented with herpes zoster. We are here by suggesting that the clinical presentation of HZ at the time of the current pandemic even in patients giving mild or no suggestive history of upper respiratory symptoms should be considered as an alarming sign for a recent subclinical SARS CoV2 infection.

Herpes zoster
SARS CoV2
COVID19
immune suppression
skin rash


Evaluating the impact of a coaching pilot on students and staff.

Abstract: A coaching pilot was developed following the publication of a number of reports that recommended a review into how student nurses are taught in clinical practice. A bespoke version of the Collaborative Learning in Practice (CLiP) model was developed, which used both coaching and peer learning to encourage students to lead the delivery of care for a designated group of patients. A senior student led a team consisting of two junior students and they were given the responsibility of directing and coordinating the team in the manner expected of a registered nurse. A qualified nurse was responsible for the supervision of the students and used a coaching approach to teach. Findings from an evaluation revealed that the students benefitted from being able to work autonomously and were able to enhance their leadership and management skills.

Underwood|Stella|S| Green|Julie|J| Walton|Rachel|R| Hackett|Kate|K| Cooke|Janet|J| Pegg|Marie|M| Armstrong|Christine|C|

D005181:Faculty, Nursing
D017144:Focus Groups
D006801:Humans
D007400:Interprofessional Relations
D007858:Learning
D000071252:Mentoring
D015402:Nursing Education Research
D015403:Nursing Evaluation Research
D015404:Nursing Methodology Research
D009740:Nursing Staff
D013338:Students, Nursing

Coaching
Student nurses
Peer learning
Mentoring
Nurse education


A review of genetic epidemiology of head and neck cancer related to polymorphisms in metabolic genes, cell cycle control and alcohol metabolism.

Abstract: The purpose of this report is to review the relationship between genetic polymorphisms involved in carcinogen metabolism, alcohol metabolism and cell-cycle control with the risk of head and neck cancer. The review was performed on available studies on genetic polymorphisms and head and neck cancer (HNC) published in PubMed up to September 2011. 246 primary articles and 7 meta-analyses were published. Among these, a statistically significant association was reported for glutathione S-transferases (GSTM1), glutathione S-transferases (GSTT1) and human microsomal epoxide hydrolase (EPHX1) genes. An increased risk for HNC was also associated reported for P53 codon 72 Pro/Pro, ALDH2 and three variants of the ADH gene: ADH1B (rs1229984), ADH7 (rs1573496) and ADH1C (rs698).

Cadoni|G|G|
Boccia|S|S|
Petrelli|L|L|
Di Giannantonio|P|P|
Arzani|D|D|
Giorgio|A|A|
De Feo|E|E|
Pandolfini|M|M|
Gallì|P|P|
Paludetti|G|G|
Ricciardi|G|G|

Head and neck cancer
Genetic polymorphisms
Genetic susceptibility


ABCG2 expression and uric acid metabolism of the intestine in hyperuricemia model rat.

Abstract: To elucidate roles of the intestine in uric acid (UA) metabolism, we examined ABCG2 expression, tissue UA content and xanthine oxidoreductase (XOR) activity in different intestinal segments. Male SD rats were assigned to control group or oxonic acid-induced hyperuricemia (HUA) group. In control rats, ABCG2 was present both in villi and crypts in each segment. Tissue UA content and XOR activity were relatively high in duodenum and jejunum. However, in HUA rats, tissue UA content was significantly elevated in the ileum, whereas it remained unaltered in other segments. Moreover, ABCG2 expression in the HUA group was upregulated both in the villi and crypts of the ileum. These data indicate that the ileum may play an important role in the extra-renal UA excretion.

Morimoto|Chikayuki|C| Tamura|Yoshifuru|Y| Asakawa|Shinichiro|S| Kuribayashi-Okuma|Emiko|E| Nemoto|Yoshikazu|Y| Li|Jinping|J| Murase|Takayo|T| Nakamura|Takashi|T| Hosoyamada|Makoto|M| Uchida|Shunya|S| Shibata|Shigeru|S|

D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2

ABCG2
Hyperuricemia
xanthine oxidoreductase
rat intestine
villin


Optimal timing of salvage radiotherapy for biochemical recurrence after radical prostatectomy: is ultra-early salvage radiotherapy beneficial?

Abstract:
BACKGROUND
The optimal timing of salvage radiotherapy for biochemical recurrence after radical prostatectomy is controversial. In particular, the prognostic significance of salvage radiotherapy delivered before a current definition of biochemical recurrence, i.e. ultra-early salvage radiotherapy, is unclear.

METHODS
We reviewed 76 patients with pT2-3N0M0 prostate cancer who underwent salvage radiotherapy for post-prostatectomy biochemical recurrence at the following three timings: ultra-early salvage radiotherapy (n = 20) delivered before meeting a current definition of biochemical recurrence (two consecutive prostate-specific antigen [PSA] values ≥0.2 ng/mL); early salvage radiotherapy (n = 40) delivered after meeting the definition but before PSA reached 0.5 ng/mL; and delayed salvage radiotherapy (n = 16) delivered after PSA reached 0.5 ng/mL. The primary endpoint was failure of salvage radiotherapy, defined as a PSA value ≥0.2 ng/mL. The log-rank test and Cox proportional hazards model were used for univariate and multivariate analyses, respectively.

RESULTS
During the follow-up period (median: 70 months), four of 20 (20 %), nine of 40 (23 %) and seven of 16 (44 %) patients failed biochemically in the ultra-early, early and delayed salvage radiotherapy groups, respectively. On univariate analyses, the outcome of delayed salvage radiotherapy was worse than the others, while there was no significant difference between ultra-early and early groups. Multivariate analysis demonstrated the presence of Gleason pattern 5, perineural invasion and delayed salvage radiotherapy as independent predictors of poorer survival.

CONCLUSIONS
No survival benefit of ultra-early salvage radiotherapy was demonstrated, whereas delayed salvage radiotherapy was associated with worse outcome as reported in previous studies. Our results may support the current recommendations that salvage radiotherapy should be undertaken after two consecutive PSA values ≥0.2 ng/mL and before reaching 0.5 ng/mL.

Salvage
Radiotherapy
Biochemical recurrence
Prostatectomy
Prostate cancer
Radiation


The effects of Alkanna tinctoria Tausch on split-thickness skin graft donor site management: a randomized, blinded placebo-controlled trial.

Abstract:
BACKGROUND
A prospective, randomized, placebo-controlled clinical trial was conducted to compare the healing effectiveness of Alkanna tinctoria (L.) Tausch (Boraginaceae) with standard dressing on wound healing at the donor site after removal of the skin graft.

METHODS
Enrolled patients were randomly allocated to receive topicalA. tinctoria extract ointment (20%) or standard dressing (dressing with base ointment) daily. Wound healing was assessed using the Bates-Jenson assessment tool at the 2nd and 4th weeks after intervention.

RESULTS
Decreases in wound score were significantly greater in the A. tinctoria group compared with the placebo group (P <0.05). The surface areas of graft donor sites in the A. tinctoria group were significantly reduced as compared with the control group at day 28 of the intervention (P < 0.05). The proportion of patients in the A. tinctoria group achieving complete wound healing within 2 to 4 weeks was 50% and 96.66%, respectively, significantly higher than in patients receiving standard care: 0% and 23.3%, respectively.

CONCLUSIONS
This clinical study showed that A. tinctoria dressing accelerates wound healing after graft harvesting.

TRIAL REGISTRATION
IRCT ID: IRCT201511165781N2 .


The effects of add-on corticosteroids on renal outcomes in patients with biopsy proven HIV associated nephropathy: a single centre study from South Africa.

Abstract:
BACKGROUND
The aim of this study was to assess, the efficacy and safety of add-on corticosteroids to antiretroviral therapy [ART] in patients with biopsy proven HIV associated nephropathy.

METHODS
All included patients had histological evidence of either collapsing or non-collapsing focal segmental glomerulosclerosis (FSGS) or podocyte and/or parietal cell hypertrophy or hyperplasia. All patients had evidence of tubulointerstitial inflammation with microcysts. Patients were randomized to ART with the addition of 1 mg/kg of corticosteroids [ART+C] or remained in the group [ART Alone] and followed for 2 years. A repeat biopsy was performed at 6 months.

RESULTS
Twenty-one patients were randomized to [ART+C] and 17 to [ART Alone]. The baseline estimated glomerular filtration rate (eGFR) was significantly lower in the [ART+C] vs. [ART Alone] group [35mls/min/1.73m2 vs. 47 mls/min/1.73m2, p = 0.015]. The [ART+C] cohort had a statistically significant improvement in median (eGFR) from baseline to last follow up compared with [ART Alone] i.e. [Δ = 25mls/min (IQR: 15;51) vs 9 mls/min (IQR: 0-24), p = 0.008]. There were no statistically significant differences between the groups when proteinuria and histology were analyzed. There were 8 deaths during the trial period, 7 from [ART+C] (Log rank p = 0.071).

CONCLUSIONS
In the [ART+C] cohort there was a significant improvement in eGFR over 2-years with increased mortality. Routine corticosteroid use cannot currently be recommended. Further investigation to define which subgroup of this cohort would safely benefit from the positive effects is required.

TRIAL REGISTRATION
ISRCTN study ID ( 56112439 ] was retrospectively registered on the 5 September 2018.

Wearne|Nicola|N|0000-0001-9917-223X
Swanepoel|Charles R|CR|
Duffield|Maureen S|MS|
Davidson|Bianca J|BJ|
Manning|Kathryn|K|
Tiffin|Nicki|N|
Boulle|Andrew|A|
Rayner|Brian L|BL|
Naidu|Priyanka|P|
Okpechi|Ikechi G|IG|

D023241:Antiretroviral Therapy, Highly Active

Corticosteroids
HIV
HIV associated nephropathy


Development of in vitro PIK3C3/VPS34 complex protein assay for autophagy-specific inhibitor screening.

Abstract: Autophagy is an important catabolic program to respond to a variety of cellular stresses by forming a double membrane vesicle, autophagosome. Autophagy plays key roles in various cellular functions. Accordingly, dysregulation of autophagy is closely associated with diseases such as diabetes, neurodegenerative diseases, cardiomyopathy, and cancer. In this sense, autophagy is emerging as an important therapeutic target for disease control. Among the autophagy machineries, PIK3C3/VPS34 complex functions as an autophagy-triggering kinase to recruit the subsequent autophagy protein machineries on the phagophore membrane. Accumulating evidence showing that inhibition of PIK3C3/VPS34 complex successfully inhibits autophagy makes the complex an attractive target for developing autophagy inhibitors. However, one concern about PIK3C3/VPS34 complex is that many different PIK3C3/VPS34 complexes have distinct cellular functions. In this study, we have developed an in vitro PIK3C3/VPS34 complex monitoring assay for autophagy inhibitor screening in a high-throughput assay format instead of targeting the catalytic activity of the PIK3C3/VPS34 complex, which shuts down all PIK3C3/VPS34 complexes. We performed in vitro reconstitution of an essential autophagy-promoting PIK3C3/VPS34 complex, Vps34-Beclin1-ATG14L complex, in a microwell plate (96-well format) and successfully monitored the complex formation in many different conditions. This PIK3C3/VPS34 complex protein assay would provide a reliable tool for the screening of autophagy-specific inhibitors.

Kim|Tae-Mi|TM|
Baek|Jong-Hyuk|JH|
Kim|Jeong Hee|JH|
Oh|Myung Sook|MS|
Kim|Joungmok|J|

D058546:Class III Phosphatidylinositol 3-Kinases

In vitro PIK3C3/VPS34 complex protein assay

Autophagy-specific inhibitor screening method


Prognostic relevance of HER2/neu in acute lymphoblastic leukemia and induction of NK cell reactivity against primary ALL blasts by trastuzumab.

Abstract: The epidermal growth factor receptor HER2/neu is expressed on various cancers and represents a negative prognostic marker, but is also a target for the therapeutic monoclonal antibody Trastuzumab. In about 30% of cases, HER2/neu is expressed on acute lymphoblastic leukemia (ALL) cells and was proposed to be associated with a deleterious prognosis. Here we evaluated clinical data from 65 ALL patients (HER2/neu+, n = 17; HER2/neu-, n = 48) with a median follow-up of 19.4 months (range 0.6-176.5 months) and observed no association of HER2/neu expression with response to chemotherapy, disease free or overall survival. In vitro, treatment of primary ALL cells (CD20+HER2/neu+, CD20+HER2/neu- and CD20-HER2/neu-) with Rituximab and Trastuzumab led to activation of NK cells in strict dependence of the expression of the respective antigen. NK reactivity was more pronounced with Rituximab as compared to Trastuzumab, and combined application could lead to additive effects in cases where both antigens were expressed. Besides providing evidence that HER2/neu expression is no risk factor in ALL patients, our data demonstrates that HER2/neu can be a promising target for Trastuzumab therapy in the subset of ALL patients with the potential to improve disease outcome.

Haen|Sebastian P|SP|
Schmiedel|Benjamin J|BJ|
Rothfelder|Kathrin|K|
Schmied|Bastian J|BJ|
Dang|Truong-Minh|TM|
Mirza|Nora|N|
Möhle|Robert|R|
Kanz|Lothar|L|
Vogel|Wichard|W|
Salih|Helmut R|HR|

D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma

HER2/neu
acute lymphoblastic leukemia
trastuzumab
rituximab
ADCC


Phenotypic and molecular insights into spinal muscular atrophy due to mutations in BICD2.

Abstract: Spinal muscular atrophy is a disorder of lower motor neurons, most commonly caused by recessive mutations in SMN1 on chromosome 5q. Cases without SMN1 mutations are subclassified according to phenotype. Spinal muscular atrophy, lower extremity-predominant, is characterized by lower limb muscle weakness and wasting, associated with reduced numbers of lumbar motor neurons and is caused by mutations in DYNC1H1, which encodes a microtubule motor protein in the dynein-dynactin complex and one of its cargo adaptors, BICD2. We have now identified 32 patients with BICD2 mutations from nine different families, providing detailed insights into the clinical phenotype and natural history of BICD2 disease. BICD2 spinal muscular atrophy, lower extremity predominant most commonly presents with delayed motor milestones and ankle contractures. Additional features at presentation include arthrogryposis and congenital dislocation of the hips. In all affected individuals, weakness and wasting is lower-limb predominant, and typically involves both proximal and distal muscle groups. There is no evidence of sensory nerve involvement. Upper motor neuron signs are a prominent feature in a subset of individuals, including one family with exclusively adult-onset upper motor neuron features, consistent with a diagnosis of hereditary spastic paraplegia. In all cohort members, lower motor neuron features were static or only slowly progressive, and the majority remained ambulant throughout life. Muscle MRI in six individuals showed a common pattern of muscle involvement with fat deposition in most thigh muscles, but sparing of the adductors and semitendinosus. Muscle pathology findings were highly variable and included pseudomyopathic features, neuropathic features, and minimal change. The six causative mutations, including one not previously reported, result in amino acid changes within all three coiled-coil domains of the BICD2 protein, and include a possible 'hot spot' mutation, p.Ser107Leu present in four families. We used the recently solved crystal structure of a highly conserved region of the Drosophila orthologue of BICD2 to further-explore how the p.Glu774Gly substitution inhibits the binding of BICD2 to Rab6. Overall, the features of BICD2 spinal muscular atrophy, lower extremity predominant are consistent with a pathological process that preferentially affects lumbar lower motor neurons, with or without additional upper motor neuron involvement. Defining the phenotypic features in this, the largest BICD2 disease cohort reported to date, will facilitate focused genetic testing and filtering of next generation sequencing-derived variants in cases with similar features.

Rossor|Alexander M|AM|
Oates|Emily C|EC|
Salter|Hannah K|HK|
Liu|Yang|Y|
Murphy|Sinead M|SM|
Schule|Rebecca|R|
Gonzalez|Michael A|MA|
Scoto|Mariacristina|M|
Phadke|Rahul|R|
Sewry|Caroline A|CA|
Houlden|Henry|H|
Jordanova|Albena|A|
Tournev|Iyailo|I|
Chamova|Teodora|T|
Litvinenko|Ivan|I|
Zuchner|Stephan|S|
Herrmann|David N|DN|
Blake|Julian|J|
Sowden|Janet E|JE|
Acsadi|Gyuda|G|
Rodriguez|Michael L|ML|
Menezes|Manoj P|MP|
Clarke|Nigel F|NF|
Auer Grumbach|Michaela|M|
Bullock|Simon L|SL|
Muntoni|Francesco|F|
Reilly|Mary M|MM|
North|Kathryn N|KN|

dominant congenital spinal muscular atrophy


Enhanced real-time cyanobacterial fluorescence monitoring through chlorophyll-a interference compensation corrections.

Abstract: In situ fluorometers can be used as a real-time cyanobacteria detection tool to maintain safe drinking and recreational water standards. However, previous studies into fluorometers have established issues arising mainly from measurement inaccuracies due to green algae interference. Therefore, this study focusses on developing correction factors from a systematic study on the impact of green algae as an interference source. This study brings a novel technique where the chlorophyll-a (Chl-a) and phycocyanin measurements are used to correct the fluorometer output for interference bias; four fluorometers were tested against three key cyanobacterial species and the relationship between phycocyanin output, green algae and cyanobacteria concentrations were investigated. Good correlation (R2 > 0.9, p-value < 0.05) was found between the fluorometer phycocyanin output and increasing green algae concentration. The optimal correction method was selected for each of the fluorometer and cyanobacteria species pairs by validating against data from the investigation of green algae as an interference source. The correction factors determined in this study reduced the measurement error for almost all the fluorometers and species tested by 21%-99% depending on the species and fluorometer, compared to previous published correction factors in which the measurement error was reduced by approximately 11%-81%. Field validation of the correction factors showed reduction in fluorometer measurement error at sites in which cyanobacterial blooms were dominated by a single species.

Choo|F|F|
Zamyadi|A|A|
Stuetz|R M|RM|
Newcombe|G|G|
Newton|K|K|
Henderson|R K|RK|

Phycocyanin
Algae and cyanobacteria
In situ probe
Source management


Active surveillance for antenatally detected ureteroceles: Predictors of success.

Abstract:
INTRODUCTION
Historically, ureteroceles were surgically treated, as patients were diagnosed after developing symptoms. However, with the advance of fetal medicine, antenatal detection has provided an opportunity to look at the natural history of ureteroceles.

OBJECTIVES
With data derived from a retrospective chart review of patients with ureteroceles that were detected antenatally, the current study aimed to determine which group of children would be at risk for failure on active surveillance. It was hypothesized that single system ureteroceles (SSU) and male patients with duplex system ureteroceles (DSU) would be ideal for observation.

METHODS
Outcomes were assessed by descriptive statistics. Kaplan-Meier curves were utilized to estimate median duration on active surveillance in both single and duplex cohorts. Breakthrough febrile urinary tract infection (fUTI) and surgery were determined by Cox regression in the duplex system cohort. Surgery was considered surveillance failure.

RESULTS
A total of 102 patients (64 females/38 males) met the criteria: 78 (76.5%) had DSU and 24 (23.5%) SSU. The overall median observation was 1.2 years (range 0.7-3.1). Follow-up ranged from 0.3 to 11.7 years for SSU, and from 0.02 to 17.3 years for DSU. The predictors of failure of active surveillance (AS) in DSU (surgical intervention) were male gender (HR 1.8, 1.0-3.3, P = 0.037), or fUTI (HR 3.1, 1.7-5.8, P = 0.002). Predictors of fUTI were contralateral hydroureter or ipsilateral hydronephrosis ± hydroureter (OR 9.5, 1.2-71.7, P = 0.028). Interestingly, vesicoureteral reflux (VUR) was not a predictor of fUTI. The SSU patients were ideal for AS, while in DSU, surveillance was successful in 30% of patients who were primarily females without contralateral hydroureter or ipsilateral hydronephrosis ± hydroureter. However, in contradiction to the hypothesis, males were at higher risk for surgical intervention in the DSU cohort.

CONCLUSION
Active surveillance is an option for patients with antenatally detected ureteroceles, but careful long term follow up is mandatory. Parents should be advised that surgical intervention may still be necessary, particularly in males with DSU.

Andrioli|V|V|
Guerra|L|L|
Keays|M|M|
Keefe|D T|DT|
Tang|K|K|
Sullivan|K J|KJ|
Garland|K|K|
Rafikov|M|M|
Leonard|M P|MP|

Ureterocele
Duplex system
Conservative management
Pediatric urology


Prescription of Potentially Inappropriate Medication in Older Inpatients of an Internal Medicine Ward: Concordance and Overlap Among the EU(7)-PIM List and Beers and STOPP Criteria.

Abstract: Background: Age-related comorbidities prone older adults to polypharmacy and to an increased risk of potentially inappropriate medication (PIM) use. This work aims to analyze the concordance and overlap among the EU(7)-PIM list, 2019 Beers criteria, and Screening Tool of Older Person's Prescriptions (STOPP) version 2 criteria and also to analyze the prevalence of PIM. Methods: A retrospective cohort study was conducted on older inpatients of an internal medicine ward. Demographic, clinical, and pharmacological data were collected, during March 2020. After PIM identification by the EU(7)-PIM list, Beers criteria, and STOPP v2 criteria, the concordance and overlap between criteria were analyzed. A descriptive analysis was performed, and all the results with a p-value lower than 0.05 were considered statistically significant. Results: A total of 616 older patients were included in the study whose median age was 85 (Q1-Q3) (78-89) years. Most of the older patients were male (51.6%), and the median (Q1-Q3) number of days of hospitalization was 17 (13-22) days. According to the EU(7)-PIM list, Beers criteria, and STOPP criteria, 79.7, 92.0, and 76.5% of older adults, respectively, used at least one PIM. A poor concordance (<63.4%) among criteria was observed. An association between PIM and the number of prescribed medicines was found in all applied criteria. Moreover, an association between the number of PIMs and diagnoses of endocrine, nutritional, and metabolic diseases, mental, behavioral, and neurodevelopmental disorders, and circulatory system diseases and days of hospitalization was observed according to Beers criteria, and that with diseases of the circulatory system and musculoskeletal system and connective tissue was observed according to STOPP criteria. Conclusion: Despite the poor concordance between the EU(7)-PIM list, 2019 Beers, and STOPP v2 criteria, this work highlights the need for more studies in inpatients to develop strategies to facilitate the identification of PIM to decrease the high prevalence of PIM in hospitalized patients. The poor concordance among criteria also highlights the need to develop new tools adapting the existing criteria to medical ward inpatients.

Perpétuo|Carla|C|
Plácido|Ana I|AI|
Rodrigues|Daniela|D|
Aperta|Jorge|J|
Piñeiro-Lamas|Maria|M|
Figueiras|Adolfo|A|
Herdeiro|Maria Teresa|MT|
Roque|Fátima|F|

potentially inappropriate medication
internal medicine ward
EU(7)-PIM list
older adults
STOPP v2 criteria
AGS 2019 Beers criteria


Castanea sativa by-products: a review on added value and sustainable application.

Abstract: Castanea sativa Mill. is a species of the family Fagaceae abundant in south Europe and Asia. The fruits (chestnut) are an added value resource in producing countries. Chestnut economic value is increasing not only for nutritional qualities but also for the beneficial health effects related with its consumption. During chestnut processing, a large amount of waste material is generated namely inner shell, outer shell and leaves. Studies on chestnut by-products revealed a good profile of bioactive compounds with antioxidant, anticarcinogenic and cardioprotective properties. These agro-industrial wastes, after valorisation, can be used by other industries, such as pharmaceutical, food or cosmetics, generating more profits, reducing pollution costs and improving social, economic and environmental sustainability. The purpose of this review is to provide knowledge about the type of chestnut by-products produced, the studies concerning its chemical composition and biological activity, and also to discuss other possible applications of these materials.

Braga|Nair|N|
Rodrigues|Francisca|F|
Oliveira|M Beatriz P P|MB|

Castanea sativa
by-products
review
sustainability
chestnut
composition


Clinical features of central nervous system involvement in patients with eosinophilic granulomatosis with polyangiitis: a retrospective cohort study in China.

Abstract:
BACKGROUND
Central nervous system (CNS) involvement is extremely rare in eosinophilic granulomatosis with polyangiitis (EGPA), but is associated with a poor prognosis in the five-factor score. This study aims to elucidate the clinical features and independently associated factors of EGPA with CNS involvement.

RESULTS
CNS involvement was observed in 17.3% (19/110) of EGPA patients from Peking Union Medical College Hospital between 2007 and 2019. We retrospectively reviewed their clinical data and analyzed the independently associated factors. Their mean age was 51.7 ± 11.56 years with no male/female predominance. Ischemic lesions were the most common manifestations, accounting for 63.2% of the 19 cases, followed by posterior reversible encephalopathy syndrome (36.8%), spinal cord involvement (15.8%), medulla oblongata involvement (15.8%), and intracranial hemorrhages (15.8%). Compared to the control group, patients with CNS involvement were of older age (51.7 ± 11.56 vs. 43.7 ± 13.78 years, p = 0.019) and had a higher ratio in the digestive tract involvement (52.6% vs. 28.6%, p = 0.042). Further multivariate analysis revealed that age, disease duration, and fever were the potential independent risk factors for CNS involvement of EGPA. Glucocorticoids combined with cyclophosphamide were the strategic therapy (94.7%). Intrathecal injections of dexamethasone and methotrexate were administered to 21.1% of the patients. Although seven patients relapsed during glucocorticoid reduction, seventeen patients finally achieved clinical remission. One patient died of acute intracerebral hemorrhage within one month, and another died of gastrointestinal perforation. Outcomes and cumulative survival show no significant differences between the two groups.

CONCLUSIONS
CNS involvement is uncommon in EGPA with various manifestations, and ischemic lesions are the most frequent. Age, disease duration, and fever are independent factors associated with CNS involvement in EGPA. The therapy of glucocorticoids combined with cyclophosphamide and intrathecal injections yields favorable responses. Acute intracranial hemorrhage and gastrointestinal perforation may be the principal causes of death.

Liu|Suying|S| Guo|Ling|L| Fan|Xiaoyuan|X| Zhang|Zhaocui|Z| Zhou|Jiaxin|J| Tian|Xinping|X| Li|Mengtao|M| Zeng|Xiaofeng|X| Wang|Li|L|0000-0003-0899-5703 Zhang|Fengchun|F|

Eosinophilic granulomatosis with polyangiitis


Choroidal origin of endogenous Candida endophthalmitis.

Abstract: Endogenous Candida endophthalmitis (ECE) has been established with microscopic histopathology, both by autopsy and experimentation, to primarily originate from and involve the choroid. Zhuang et al. examined a series of patients with ECE using spectral-domain optical coherence tomography (SD-OCT) imaging and present a new classification scheme. The authors conclude the majority of lesions are primarily retinal in location without report of choroidal involvement. This discrepancy may be explained by posterior shadowing artifact and lack of discernment from associated retinal findings like infarction. These considerations are necessary in reviewing SD-OCT, characterizing ECE, and proposing new classification systems.

Spectral-domain optical coherence tomography


Functional aspects of the interaction between interleukin-8 and sulfated glycosaminoglycans.

Abstract: During the immune response, the cytokine interleukin 8 (IL-8, CXCL8) functions as a strong chemoattractant for polymorphonuclear leukocytes helping to direct these cells to infected/injured sites. This review focuses on the interaction of IL-8 with sulfated glycosaminoglycans expressed on cell surfaces and the extracellular matrix. This interaction contributes to the recruitment of polymorphonuclear cells from blood, penetration of these cells through the vessel wall, and their directed migration to inflammatory sites. Regulatory aspects of the interplay between IL-8 and heparan sulfate, the most abundant glycosaminoglycan, are highlighted. In this field, the large natural heterogeneity of glycosaminoglycans represents a great challenge that impedes the modeling of IL-8 functions. The interaction of IL-8 with newly developed artificial sulfated hyaluronan derivatives is also considered as these artificial substrates are an important tool for development of new materials in regenerative medicine.

Pichert|Annelie|A| Schlorke|Denise|D| Franz|Sandra|S| Arnhold|Juergen|J|

interleukin-8
glycosaminoglycans
polmorphonuclear leukocytes


Thieno[3,4-c]pyrrole-4,6-dione-3,4-difluorothiophene Polymer Acceptors for Efficient All-Polymer Bulk Heterojunction Solar Cells.

Abstract: Branched-alkyl-substituted poly(thieno[3,4-c]pyrrole-4,6-dione-alt-3,4-difluorothiophene) (PTPD[2F]T) can be used as a polymer acceptor in bulk heterojunction (BHJ) solar cells with a low-band-gap polymer donor (PCE10) commonly used with fullerenes. The "all-polymer" BHJ devices made with PTPD[2F]T achieve efficiencies of up to 4.4 %. While, to date, most efficient polymer acceptors are based on perylenediimide or naphthalenediimide motifs, our study of PTPD[2F]T polymers shows that linear, all-thiophene systems with adequately substituted main chains can also be conducive to efficient BHJ solar cells with polymer donors.

Liu|Shengjian|S|
Kan|Zhipeng|Z|
Thomas|Simil|S|
Cruciani|Federico|F|
Brédas|Jean-Luc|JL|
Beaujuge|Pierre M|PM|

polymers
solar cells
density-functional calculations
electron microscopy
materials science


Cancellous and Cortical Bone Microarchitectures of Femoral Neck in Rheumatoid Arthritis and Osteoarthritis Compared with Donor Controls.

Abstract: This study investigated the 3D microarchitecture of cancellous and cortical bones of the femoral neck in rheumatoid arthritis (RA), osteoarthritis (OA) and donor controls. 26 femoral necks (including heads) were harvested during total hip replacement surgeries in 11 patients with RA (mean age 66.7 ± 12.8 years) and 15 patients with OA (67.3 ± 8.4 years). Femoral heads/necks were also harvested from 8 donors (74.9 ± 10.2 years). Bone samples of 10 mm thickness were prepared from each femoral neck and scanned with micro-CT to evaluate microarchitectural parameters. The RA and OA samples showed no significant differences in microarchitectural parameters in cancellous or cortical bone. Compared with the donor controls, bone volume fraction in RA and OA cancellous bone was significantly greater, the structure model index in OA was significantly lower, and the surface density in RA was significantly greater. The RA bone tissues showed erosion and marked osteophyte formation. This study demonstrated that RA and OA have similar trends of overall microarchitectural degeneration in the femoral neck, despite marked erosion in RA bone and osteophyte formation in OA bone. However, we could not eliminate the possibility of local differences between RA and OA bone. The age-related bone loss in RA and OA was less severe than those of normal ageing and osteoporosis, suggesting a compensatory effect of the diseases to increase bone density.

Wang|Bailiang|B| Overgaard|Søren|S| Chemnitz|John|J| Ding|Ming|M|

Femoral neck
Rheumatoid arthritis
Osteoarthritis
3D microarchitecture
Cancellous/cortical bones


Evolution of peripheral blood T lymphocyte subsets after allogenic or autologous hematopoietic stem cell transplantation.

Abstract: With the aim to search for differences in T cell reconstitution after allogenic or autologous hematopoietic stem cell transplantation (HSCT), we characterized peripheral blood T-cell subsets by means of flow cytometry, in adult patients who had undergone either allogenic (n=23) or autologous (n=29) HSCT for the treatment of hematological malignancies. The patients were followed every 3 months for 21 months after HSCT. Compared to healthy controls (n=20 blood donors), the two transplanted groups displayed (i) a CD4 lymphopenia, (ii) a low percentage of naive T cells, (iii) high percentages of memory T cells and of activated T cells (HLA-DR+, CD25+) and high percentages of CD4 T cells with a high expression of CD25. The levels of TRECs (TCR rearrangement excision circles) were not significantly different between the two groups. In total, the differences of the nature and the speed of T lymphocyte reconstitution observed between the two patient groups were minor. This leads us to conclude that in allografted patients, lymphocyte activation as well as many other disturbances of subpopulations of peripheral blood lymphocytes are probably not related to the allogenicity of the graft, but are due to the expansion of T cells transfused with HSC and slow differentiation of T lymphocytes in the thymus progressively colonized by bone marrow-derived T-cell precursors.

Puissant-Lubrano|Bénédicte|B| Huynh|Anne|A| Attal|Michel|M| Blancher|Antoine|A|

D018380:Hematopoietic Stem Cell Transplantation

D053645:Interleukin-2 Receptor alpha Subunit

Hematopoietic stem cell transplantation
T lymphocyte reconstitution
Allogenic HSCT
Autologous HSCT


Surprises in the 3'-end: 'U' can decide too!

Abstract: RNA molecules are subjected to post-transcriptional modifications that might determine their maturation, activity, localization and stability. These alterations can occur within the RNA molecule or at its 5'- or 3'- extremities, and are essential for gene regulation and proper function of the RNA. One major type of modification is the 3'-end addition of nontemplated nucleotides. Polyadenylation is the most well studied type of 3'-RNA modification, both in eukaryotes and prokaryotes. The importance of 3'-oligouridylation has recently gained attention through the discovery of several types of uridylated-RNAs, by the existence of enzymes that specifically add poly(U) tails and others that preferentially degrade these tails. Namely, Dis3L2 is a 3'-5' exoribonuclease from the RNase II/RNB family that has been shown to act preferentially on oligo(U)-tailed transcripts. Our understanding of this process is still at the beginning, but it is already known to interfere in the regulation of diverse RNA species in most eukaryotes. Now that we are aware of the prevalence of RNA uridylation and the techniques available to globally evaluate the 3'-terminome, we can expect to make rapid progress in determining the extent of terminal oligouridylation in different RNA populations and unravel its impact on RNA decay mechanisms. Here, we sum up what is known about 3'-RNA modification in the different cellular compartments of eukaryotic cells, the conserved enzymes that perform this 3'-end modification and the effectors that are selectively activated by this process.

Viegas|Sandra C|SC|
Silva|Inês J|IJ|
Apura|Patricia|P|
Matos|Rute G|RG|
Arraiano|Cecilia M|CM|

Dis3L2
RNB family
uridylation
RNA decay
3′-RNA modification
TUTase
exonuclease
let-7
microRNA (miRNA)
ncPAP


Prognostic factors in salvage surgery for recurrent head and neck cancer: A systematic review and meta-analysis.

Abstract:
INTRODUCTION
Although salvage surgery (SS) is considered the best curative choice in recurrent head and neck cancer, the identification of patients who can benefit the most from this treatment is challenging.

METHODS
We systematically reviewed the prognostic role of pre- and post-surgery factors in patients undergoing SS for recurrent head and neck cancer (oral cavity, oropharynx, hypopharynx, and larynx).

RESULTS
Twenty-five studies met the inclusion criteria out of 1280 screened citations. Pre-surgery factors significantly associated with worse overall survival were age>60 years, advanced initial stage, early recurrence, and regional recurrence; no heterogeneity between study emerged. Among post- surgery factors, worse survival emerged for positive surgical margins, extracapsular extension and perineural invasion.

CONCLUSION
The identification of pre-surgery factors associated with poor outcomes may help the selection of the best candidate to SS; alternative treatments should be considered for high-risk patients. Post-surgery predictors of worse prognosis may guide clinicians in tailoring patients' surveillance.

Lupato|Valentina|V| Giacomarra|Vittorio|V| Alfieri|Salvatore|S| Fanetti|Giuseppe|G| Polesel|Jerry|J|

Salvage surgery
Head and neck cancer
Overall survival
Oral cancer
Progression-free survival


Sexual Transmission of Lyme Borreliosis? The Question That Calls for an Answer.

Abstract: Transmission of the causative agents of numerous infectious diseases might be potentially conducted by various routes if this is supported by the genetics of the pathogen. Various transmission modes occur in related pathogens, reflecting a complex process that is specific for each particular host-pathogen system that relies on and is affected by pathogen and host genetics and ecology, ensuring the epidemiological spread of the pathogen. The recent dramatic rise in diagnosed cases of Lyme borreliosis might be due to several factors: the shifting of the distributional range of tick vectors caused by climate change; dispersal of infected ticks due to host animal migration; recent urbanization; an increasing overlap of humans' habitat with wildlife reservoirs and the environment of tick vectors of Borrelia; improvements in disease diagnosis; or establishment of adequate surveillance. The involvement of other bloodsucking arthropod vectors and/or other routes of transmission (human-to-human) of the causative agent of Lyme borreliosis, the spirochetes from the Borrelia burgdorferi sensu lato complex, has been speculated to be contributing to increased disease burden. It does not matter how controversial the idea of vector-free spirochete transmission might seem in the beginning. As long as evidence of sexual transmission of Borrelia burgdorferi both between vertebrate hosts and between tick vectors exists, this question must be addressed. In order to confirm or refute the existence of this phenomenon, which could have important implications for Lyme borreliosis epidemiology, the need of extensive research is obvious and required.

Lyme borreliosis
spirochete
sexually transmitted disease
tick-borne disease


Selective pharmacological blockade of the 5-HT7 receptor attenuates light and 8-OH-DPAT induced phase shifts of mouse circadian wheel running activity.

Abstract: Recent reports have illustrated a reciprocal relationship between circadian rhythm disruption and mood disorders. The 5-HT7 receptor may provide a crucial link between the two sides of this equation since the receptor plays a critical role in sleep, depression, and circadian rhythm regulation. To further define the role of the 5-HT7 receptor as a potential pharmacotherapy to correct circadian rhythm disruptions, the current study utilized the selective 5-HT7 antagonist JNJ-18038683 (10 mg/kg) in three different circadian paradigms. While JNJ-18038683 was ineffective at phase shifting the onset of wheel running activity in mice when administered at different circadian time (CT) points across the circadian cycle, pretreatment with JNJ-18038683 blocked non-photic phase advance (CT6) induced by the 5-HT1A/7 receptor agonist 8-OH-DPAT (3 mg/kg). Since light induced phase shifts in mammals are partially mediated via the modulation of the serotonergic system, we determined if JNJ-18038683 altered phase shifts induced by a light pulse at times known to phase delay (CT15) or advance (CT22) wheel running activity in free running mice. Light exposure resulted in a robust shift in the onset of activity in vehicle treated animals at both times tested. Administration of JNJ-18038683 significantly attenuated the light induced phase delay and completely blocked the phase advance. The current study demonstrates that pharmacological blockade of the 5-HT7 receptor by JNJ-18038683 blunts both non-photic and photic phase shifts of circadian wheel running activity in mice. These findings highlight the importance of the 5-HT7 receptor in modulating circadian rhythms. Due to the opposite modulating effects of light resetting between diurnal and nocturnal species, pharmacotherapy targeting the 5-HT7 receptor in conjunction with bright light therapy may prove therapeutically beneficial by correcting the desynchronization of internal rhythms observed in depressed individuals.

Shelton|Jonathan|J|
Yun|Sujin|S|
Losee Olson|Susan|S|
Turek|Fred|F|
Bonaventure|Pascal|P|
Dvorak|Curt|C|
Lovenberg|Timothy|T|
Dugovic|Christine|C|

5-HT7 receptor
phase shift
circadian rhythms
mood
depression
non-photic
photic
serotonin


Sci-Sat AM: Brachy - 10: Adaptation of the CVT algorithm for catheter optimization in high dose rate brachytherapy.

Abstract:
INTRODUCTION
In interstitial high dose rate (HDR) brachytherapy, the number and positions of the catheter are usually fixed by the use of a template, without considering tumor size and shape. In this work, we present a simple and fast method to optimize both the number and position of catheters, using a modified version of the Centroidal Voronoi Tessellations (CVT) algorithm.

METHODS
8 prostate HDR clinical cases were chosen randomly to test our method. The treatment plan was obtained from a research version of IPSA. Clinically relevant dosimetric parameters were computed to evaluate our method and help optimizing the CVT algorithm parameters. Plans were generated with a specified number of catheters ranging from 9 to 18 and compared to the clinical cases with 17 catheters.

RESULTS
The computation time to optimize the positions of a specific number of catheters was 1.5 s. The prostate V100 was better than the clinical case up to 12 catheters. Plans with 9 or less catheters would not be clinically acceptable in terms of prostate V100 and D90. High conformity is achieved whether the number of catheters used. The V75 of the bladder seems slightly higher, but not significant clinically. All other dosimetric indices are as good as the clinical plan.

CONCLUSION
We have devised a simple, fast and efficient method to optimize the number and position of catheters in HDR brachytherapy. Ultimately, this catheter optimization algorithm could be coupled with a 3D ultrasound system to allow real-time guidance and planning for any interstitial brachytherapy sites.

Poulin|E|E|
Fekete|Ca Collins|CC|
Morrier|J|J|
Varfalvy|N|N|
Pouliot|J|J|
Beaulieu|L|L|

Brachytherapy Cancer Dosimetry Ultrasonography


Volatile flavour profile of reduced alcohol wines fermented with the non-conventional yeast species Metschnikowia pulcherrima and Saccharomyces uvarum.

Abstract: Production of quality wines with decreased alcohol concentration continues to be one of the major challenges facing wine producers. Therefore, there is considerable interest in the isolation or generation of wine yeasts less efficient at transforming grape sugars into ethanol. We recently demonstrated that Metschnikowia pulcherrima AWRI1149 and Saccharomyces uvarum AWRI2846 were both able to produce reduced alcohol wine when used in sequential inoculation with Saccharomyces cerevisiae. This effect is additive when both strains are co-inoculated in grape must. Here we describe the volatile flavour profile of Chardonnay and Shiraz wines produced with these two strains. Wines fermented with M. pulcherrima showed concentrations of ethyl acetate likely to affect negatively wine aroma. Wines fermented with S. uvarum and with a combination of M. pulcherrima and S. uvarum were characterised by increased concentrations of 2-phenyl ethanol and 2-phenylethyl acetate, both associated with positive sensory attributes.

Varela|C|C| Sengler|F|F| Solomon|M|M| Curtin|C|C|

Flavour
Wine
Yeast
Low alcohol
non-Saccharomyces


Randomized, phase II trial of sequential hepatic arterial infusion chemotherapy and sorafenib versus sorafenib alone as initial therapy for advanced hepatocellular carcinoma: SCOOP-2 trial.

Abstract:
BACKGROUND
The efficacy of hepatic arterial infusion chemotherapy (HAIC) for advanced hepatocellular carcinoma (HCC) remains unclear. We conducted a multi-center randomized phase II study comparing a sequential HAIC-sorafenib regimen versus sorafenib alone as an initial therapy for HCC.

METHODS
Patients were randomly assigned (ratio, 1:1) to receive sequential HAIC with cisplatin followed by sorafenib (HAIC group, n = 35) or sorafenib alone (sorafenib group, n = 33) as an initial therapy. The primary endpoint was the one-year survival rate. Secondary endpoint included overall survival (OS), the 2-year survival rate, the time-to-progression (TTP), the objective response rate (ORR), the disease control rate (DCR), and safety.

RESULTS
For the primary endpoint, the one-year survival rates were 46% in the HAIC group and 58% in the sorafenib group. The median OS period was 10.0 months (95% CI, 7.0-18.8) in the HAIC group and 15.2 months (95% CI, 8.2-19.7) in the sorafenib group (hazard ratio [HR], 1.08; 95% CI, 0.63 to 1.86, P = 0.78). The median TTP, ORR and DCR in the HAIC group were 2.8 months (95% CI, 1.7-5.5), 14.3, and 45.7%, respectively, while those in the sorafenib group were 3.9 months (95% CI, 2.3-6.8), 9.1, and 45.5%, respectively. No unexpected adverse events related to HAIC or sorafenib were observed in either group.

CONCLUSIONS
Sequential HAIC with cisplatin and sorafenib does not improve the survival benefit, compared with sorafenib alone, when used as an initial therapy for advanced HCC. However, this study was underpowered in regard to its primary and secondary endpoints, so the results should be interpreted with caution.

TRIAL REGISTRATION
UMIN ID 000006147 , registration data: August 11, 2011.

D000971:Antineoplastic Combined Chemotherapy Protocols

Hepatic arterial infusion chemotherapy
Sorafenib
Hepatocellular carcinoma
Cisplatin
Sequential treatment


The changing forms and expectations of peer review.

Abstract: The quality and integrity of the scientific literature have recently become the subject of heated debate. Due to an apparent increase in cases of scientific fraud and irreproducible research, some have claimed science to be in a state of crisis. A key concern in this debate has been the extent to which science is capable of self-regulation. Among various mechanisms, the peer review system in particular is considered an essential gatekeeper of both quality and sometimes even integrity in science. However, the allocation of responsibility for integrity to the peer review system is fairly recent and remains controversial. In addition, peer review currently comes in a wide variety of forms, developed in the expectation they can address specific problems and concerns in science publishing. At present, there is a clear need for a systematic analysis of peer review forms and the concerns underpinning them, especially considering a wave of experimentation fuelled by internet technologies and their promise to improve research integrity and reporting. We describe the emergence of current peer review forms by reviewing the scientific literature on peer review and by adding recent developments based on information from editors and publishers. We analyse the rationale for developing new review forms and discuss how they have been implemented in the current system. Finally, we give a systematisation of the range of discussed peer review forms. We pay detailed attention to the emergence of the expectation that peer review can maintain 'the integrity of science's published record', demonstrating that this leads to tensions in the academic debate about the responsibilities and abilities of the peer review system.

Peer review
Innovation
Scientific integrity
Scientific misconduct
Scientific publishing


Advanced nanoscale carrier-based approaches to overcome biopharmaceutical issues associated with anticancer drug 'Etoposide'.

Abstract: Etoposide (ETS), topoisomerase-II inhibitor, is a first-line anticancer therapeutics used in diverse cancer types. However, the therapeutic potential of this molecule has mainly impeded due to its detrimental toxicity profile, unfavorable rejection by the cancer cells due to P-glycoprotein (P-gp) efflux activity, and rapid hepatic clearance through extensive metabolism by Cytochrome-P450. To increase the therapeutic potency without significant adverse effects, the implication of novel ETS-nanoformulation strategies have recommended mainly. Nanomedicine based nanoformulation approaches based on nanoparticles (NPs), dendrimers, carbon-nanotubes (CNTs), liposomes, polymeric micelles, emulsions, dendrimers, solid-lipid NPs, etc offers immense potential opportunities to improve the therapeutic potential of pharmaceutically problematic drugs. This review provides an up-to-date argument on the work done in the field of nanomedicine to resolve pharmacokinetic and pharmacodynamic issues associated with ETS. The review also expounds the progress in regards to the regulatory, patenting and clinical trials related to the innovative formulation aspects of ETS.

Choudhury|Hira|H|
Maheshwari|Rahul|R|
Pandey|Manisha|M|
Tekade|Muktika|M|
Gorain|Bapi|B|
Tekade|Rakesh Kumar|RK|

Patent and clinical trials
Etoposide delivery
Etoposide solubility
Etoposide toxicity
Pharmacological advances


Activities of the Right Temporo-Parieto-Occipital Junction Reflect Spatial Hearing Ability in Cochlear Implant Users.

Abstract: Spatial hearing is critical for us not only to orient ourselves in space, but also to follow a conversation with multiple speakers involved in a complex sound environment. The hearing ability of people who suffered from severe sensorineural hearing loss can be restored by cochlear implants (CIs), however, with a large outcome variability. Yet, the causes of the CI performance variability remain incompletely understood. Despite the CI-based restoration of the peripheral auditory input, central auditory processing might still not function fully. Here we developed a multi-modal repetition suppression (MMRS) paradigm that is capable of capturing stimulus property-specific processing, in order to identify the neural correlates of spatial hearing and potential central neural indexes useful for the rehabilitation of sound localization in CI users. To this end, 17 normal hearing and 13 CI participants underwent the MMRS task while their brain activity was recorded with a 256-channel electroencephalography (EEG). The participants were required to discriminate between the probe sound location coming from a horizontal array of loudspeakers. The EEG MMRS response following the probe sound was elicited at various brain regions and at different stages of processing. Interestingly, the more similar this differential MMRS response in the right temporo-parieto-occipital (TPO) junction in CI users was to the normal hearing group, the better was the spatial hearing performance in individual CI users. Based on this finding, we suggest that the differential MMRS response at the right TPO junction could serve as a central neural index for intact or impaired sound localization abilities.

Schäfer|Eusebia|E|
Vedoveli|Ana-Elena|AE|
Righetti|Giulia|G|
Gamerdinger|Philipp|P|
Knipper|Marlies|M|
Tropitzsch|Anke|A|
Karnath|Hans-Otto|HO|
Braun|Christoph|C|
Li Hegner|Yiwen|Y|

CI
auditory
repetition suppression
EEG
TPO junction


Epidemiology of bronchiectasis in the UK: Findings from the British lung foundation's 'Respiratory health of the nation' project.

Abstract: Key findings of this national survey of non-cystic fibrosis bronchiectasis epidemiology were that its prevalence, incidence and mortality have all increased over recent years; we estimate that around 212,000 people are currently living with bronchiectasis in the UK, very much higher than commonly quoted figures. Bronchiectasis is more common in females than males; 60% of diagnoses are made in the over-70 age group. Regional differences in prevalence, incidence, mortality, and hospital admission were identified. An intriguing finding was that bronchiectasis is more commonly diagnosed in the least deprived sections of the population, in contrast to other respiratory disorders.

Snell|Noel|N|
Gibson|Jack|J|
Jarrold|Ian|I|
Quint|Jennifer K|JK|


Effect of indoor-generated airborne particles on radon progeny dynamics.

Abstract: In order to investigate the interaction between radon progeny and particles, an experimental campaign was carried out in a radon chamber at the Italian National Institute of Ionizing Radiation Metrology, quantifying the amount of attached and unattached radon daughters present in air, as well as the equilibrium factor in the presence of particles generated through indoor sources. A fixed radon concentration was maintained, while particles were generated using incense sticks, mosquito coils and gas combustion. Aerosols were characterized in terms of particle concentrations and size distributions. Simultaneously, radon concentration and attached/unattached potential alpha energy concentration in the air were continuously monitored by two different devices, based on alpha spectroscopy techniques. The presence of particles was found to affect the attached fraction of radon decay products, in such a way that the particles acted as a sink for radionuclides. In terms of sources which emit large particles (e.g. incense, mosquito coils), which greatly increase particle surface area concentrations, the Equilibrium Factor was found to double with respect to the background level before particle generation sessions. On the contrary, the radon decay product dynamics were not influenced by gas combustion processes, mainly due to the small surface area of the particles emitted.

Trassierra|C Vargas|CV|
Stabile|L|L|
Cardellini|F|F|
Morawska|L|L|
Buonanno|G|G|

Airborne particles
Radon
Radon progeny
Equilibrium factor
Indoor air quality


Developmental Foundations of Children's Fraction Magnitude Knowledge.

Abstract: The conceptual insight that fractions represent magnitudes is a critical yet daunting step in children's mathematical development, and the knowledge of fraction magnitudes influences children's later mathematics learning including algebra. In this study, longitudinal data were analyzed to identify the mathematical knowledge and domain-general competencies that predicted 8th and 9th graders' (n=122) knowledge of fraction magnitudes and its cross-grade gains. Performance on the fraction magnitude measures predicted 9th grade algebra achievement. Understanding and fluently identifying the numerator-denominator relation in 7th grade emerged as the key predictor of later fraction magnitudes knowledge in both 8th and 9th grades. Competence at using fraction procedures, knowledge of whole number magnitudes, and the central executive contributed to 9th but not 8th graders' fraction magnitude knowledge, and knowledge of whole number magnitude contributed to cross-grade gains. The key results suggest fluent processing of numerator-denominator relations presages students' understanding of fractions as magnitudes and that the integration of whole number and fraction magnitudes occurs gradually.

Mou|Yi|Y|
Li|Yaoran|Y|
Hoard|Mary K|MK|
Nugent|Lara D|LD|
Chu|Felicia W|FW|
Rouder|Jeffrey N|JN|
Geary|David C|DC|

fractions
mathematics
Longitudinal study
in-class attention
intelligence
mathematical cognition
working memory


The Regulation of Exosome-Derived miRNA on Heterogeneity of Macrophages in Atherosclerotic Plaques.

Abstract: Exosomes are nanosized vesicles secreted by most cells, which can deliver a variety of functional lipids, proteins, and RNAs into the target cells to participate in complex intercellular communications. Cells respond to certain physical, chemical, and biological stimuli by releasing exosomes. Exosomes are rich in small molecules of RNA, including miRNAs and mRNAs, which have been demonstrated to have certain functions in recipient cells. Recent studies on single-cell RNA sequences have revealed the transcription and the heterogeneity of macrophages in Ldlr-/-mice fed with a high-fat diet. Five macrophage populations were found in the atherosclerotic plaques. It is worth noting that these subset populations of macrophages seem to be endowed with different functions in lipid metabolism and catabolism. A total of 100 differentially expressed mRNAs were selected for these subset populations. Importantly, these macrophage populations were also present in human advanced atherosclerosis. To clarify the specific functions and the regulatory mechanism of these macrophage populations, we extracted exosome RNAs from the plasma of patients with chronic coronary artery disease (CAD) and performed RNA sequencing analysis. Compared with the healthy control, a total of 14 miRNAs were significantly expressed in these patients. A total of 5,248 potential mRNAs were predicted by the bioinformatics platform. Next, we determined the outcome of the intersection of these predicted mRNAs with 100 mRNAs expressed in the above-mentioned five macrophage populations. Based on the screening of miRNA-mRNA pairs, a co-expression network was drawn to find out the key RNAs. Three down-regulated miRNAs and five up-regulated mRNAs were selected for validation by real-time RT-PCR. The results showed that the expression of miR-4498 in plasma exosomes was lower than that in the healthy control, and the expressions of Ctss, Ccr2 and Trem2 mRNA in peripheral blood mononuclear cells isolated from CAD patients were higher. In order to clarify the regulatory mechanism, we established a co-culture system in vitro. Studies have shown that the uptake of exosomes from CAD patients can up-regulate the expression of Ctss, Trem2, and Ccr2 mRNA in THP-1 cells induced by lipopolysaccharide. Our findings revealed a unique relationship between the transcriptional signature and the phenotypic heterogeneity of macrophage in the atherosclerotic microenvironment.

Li|Ximing|X| He|Xinyong|X| Wang|Junyan|J| Wang|Dan|D| Cong|Peiwei|P| Zhu|Aisong|A| Chen|Wenna|W|

miRNA macrophages exosomes atherosclerosis networks


Isolation, diversity and acetylcholinesterase inhibitory activity of the culturable endophytic fungi harboured in Huperzia serrata from Jinggang Mountain, China.

Abstract: Huperzia serrata has many important medicinal properties with proven pharmacological potential. Some of these properties may be mediated by its endophytic fungi. To test this hypothesis, in the present study, we provided a first insights into evaluating the species composition and acetylcholinesterase (AChE) inhibitory activity of the culturable endophytic fungi of H. serrata from the regional at Jinggang Mountain in southeastern China. A total number of 885 fungal isolates distributed across 44 genera and 118 putative species were obtained from 1422 fragments of fine H. serrata roots, stems and leaves base on ITS-rDNA sequences BLAST analysis. The endophytic fungi were phylogenetically diverse and species-rich, with high rate of colonization and isolation. The assemble of endophytic fungi consisted mainly of Ascomycota (97.15%), followed by Basidiomycota (1.92%) and unknown fungal species (0.90%). Colletotrichum (64.29%), Phyllosticta (3.39%), Hypoxylon (2.81%), Xylaria (2.25%) and Nigrospora (2.04%) were the most abundant genera, whereas the remaining genera were infrequent groups. Although, roots yielded low abundance strains, the diverse and species-rich were both higher than that of stems and leaves. In addition, out of the 247 endophytic fungi strains determinated, 221 fungal extracts showed AChE inhibition activities in vitro. Among them, 22 endophytic fungi strains achieved high inhibitory activity (≥50%) on AChE which belongs to 13 genera and five incertae sedis strains. Four endophytic fungi designated as JS4 (Colletotrichum spp.), FL14 (Ascomycota spp.), FL9 (Sarcosomataceae spp.) and FL7 (Dothideomycetes spp.) were displayed highly active (≥80%) against AChE, which the inhibition effects were even more intense than the positive control. Our findings highlight that H. serrata grown in Jinggang Mountain harbors a rich and fascinating endophytic fungus community with potential AChE inhibitory activity, which could further broaden the natural acetylcholinesterase inhibitors resources used for Alzheimer's disease treatment.

Wang|Ya|Y| Lai|Zheng|Z| Li|Xi-Xi|XX| Yan|Ri-Ming|RM| Zhang|Zhi-Bin|ZB| Yang|Hui-Lin|HL| Zhu|Du|D|


Gold Nanoparticles for X-ray Microtomography of Neurons.

Abstract: Commonly used methods to visualize the biological structure of brain tissues at subcellular resolution are confocal microscopy and two-photon microscopy. Both require slicing the sample into sections of a few tens of micrometers. The recent developments in X-ray microtomography enable three-dimensional imaging at sub-micrometer and isotropic resolution with larger biological samples. In this work, we developed and compared original microtomography methods and staining protocols to improve the contrast for in vitro mouse neuron imaging. Using Golgi's method to stain neurons randomly, we imaged the whole set of mouse brain structures. For specific and nonrandom neuron labeling, we conjugated 20 nm gold nanoparticles to antibodies used in the immunohistochemistry (IHC) method, using anti-NeuN to label specifically neuronal nuclei. We applied an original subtraction dual-energy method for microtomography in the vicinity of the Au L-III absorption edge and compared image reconstructions to confocal microscopy images acquired on the same samples. The results show the possibility to characterize the 3D entire brain structure of mice. They demonstrated a high contrast and neuron detection improvement by applying the dual-energy method coupled to IHC staining.

Depannemaecker|Damien|D|
Santos|Luiz E Canton|LEC|
de Almeida|Antonio-Carlos Guimarães|AG|
Ferreira|Gustavo B S|GBS|
Baraldi|Giovanni L|GL|
Miqueles|Eduardo X|EX|
de Carvalho|Murilo|M|
Costa|Gabriel Schubert Ruiz|GSR|
Marques|Marcia J Guimarães|MJG|
Scorza|Carla A|CA|
Rinkel|Jean|J|0000-0001-9980-0304

gold nanoparticles
immunohistochemistry
Brain imaging
dual-energy X-ray microtomography
synchrotron


Complementary and alternative medicine use: Results from a descriptive study of pregnant women in Udi local Government area of Enugu state, Nigeria.

Abstract:
BACKGROUND
The use of CAM by pregnant women is very popular in developed countries. The trend is increasing globally and lack of evidence of safety particularly when used during pregnancy may lead to complications. Pregnancy is a vulnerable period especially during the first trimester. There is scarcity of empirical evidence on CAM use particularly among women in Udi LGA of Enugu State and South East Nigeria. Moreover, studies carried out in Nigeria have been limited to herbal medicine use, which is one aspect of CAM. This study was designed to obtain information on the use of Complementary and Alternative Medicine among pregnant women.

METHODS
The study was a cross sectional descriptive survey of 396 pregnant women systematically drawn from twenty political wards in Udi Local Government Area (LGA) of Enugu State. Interviewer administered questionnaire developed by the researchers was used for data collection. Data were analyzed using descriptive statistics.

RESULTS
Majority (82.1%) of the pregnant women in Udi LGA used CAM during pregnancy out of which 53.8% had used CAM in previous pregnancies. CAM used ranges from one single type to sixteen different types with biological products eg, herbal tea, herbal mixture being the most commonly used CAM. Whereas most (89.5%) of the CAM used by pregnant women was consumed orally, approximately half of the pregnant women used CAM together with conventional medicine.

CONCLUSION
The use of CAM by women during pregnancy was high in Udi LGA. Therefore, maternity care providers especially midwives need to elicit CAM commonly used by women during pregnancy and counsel them appropriately for best care and safety. Researchers should focus on establishing the efficacy of CAM products.

Onyiapat|Jane-Lovena|JL| Okafor|Chinyelu|C| Okoronkwo|Ijeoma|I| Anarado|Agnes|A| Chukwukelu|Ekene|E| Nwaneri|Ada|A| Okpala|Pat|P|

Complementary and alternative medicine
Use
Pregnant women


Herpes Zoster, Hepatitis C, and Tuberculosis Risk with Apremilast Compared to Biologics, DMARDs and Corticosteroids to Treat Psoriasis and Psoriatic Arthritis.

Abstract:
Purpose
Psoriasis and psoriatic arthritis (PsA) are associated with an increased infection risk. In this cohort study of patients with treated psoriasis or PsA, we used MarketScan (2014-2018) to estimate rates of herpes zoster, hepatitis C (HepC) and tuberculosis (TB) with apremilast compared to other systemic treatments.

Materials and Methods
Patients were exposed from first apremilast [APR], DMARD, TNF-inhibitor [TNF], IL-inhibitor [IL], or corticosteroids [CS] prescription after March 21, 2014. Study exposures were APR, DMARDs only, TNF-only, IL-only, CS-only, DMARDs+CS, TNF+DMARDs and/or CS, IL+DMARDs and/or CS. Cases had treated herpes zoster, HepC, or TB event. We calculated incidence rates (IRs) [95% confidence intervals] per 1000 patient-years.

Results
The study population included 131,604 patients. For herpes zoster (N=2271), IRs were highest for users of DMARDs+CS (12.5 [9.8-15.7]), CS-only (12.5 [10.4-14.1]), and TNF+DMARDs and/or CS (11.9 [10.6-13.4]), compared with DMARDs only (9.9 [8.7-11.2]). IRs were lowest for users of IL-only (6.7 [5.8-7.8]) and APR (7.0 [5.8-8.4]). IRs of HepC (N=150) and TB (N=81) were low and between-treatment differences were not significant.

Conclusion
Rates of herpes zoster varied by treatment: highest among those who received polytherapy, lowest in users of apremilast only. IRs for HepC and TB were low for all exposures.

herpes zoster
hepatitis C
tuberculosis
apremilast
psoriasis
psoriatic arthritis


In Vitro Transcription to Study WT1 Function.

Abstract: In vitro transcription methods using mammalian nuclear extracts have been available for over 30 years and have allowed sophisticated biochemical analyses of the transcription process. This method has been extensively used to study the basic mechanisms of transcription, allowing the identification of the general transcription factors and elucidation of their mechanisms of action. Gene-specific transcriptional regulators have also been studied using in vitro transcription. This has facilitated the identification of their cofactors and provided information on their function that is invaluable to facilitate their study in a more physiological setting. Here we describe the application of in vitro transcription methods to study the mechanism of action of WT1. Coupling transcription assays with methods to purify transcription complexes, and protein affinity chromatography, has provided insights into how WT1 can both positively and negatively regulate transcription.

D002467:Cell Nucleus
D002846:Chromatography, Affinity
D006367:HeLa Cells
D006657:Histones
D006801:Humans
D066298:In Vitro Techniques
D011994:Recombinant Proteins
D014158:Transcription, Genetic
D025721:WT1 Proteins

Transcription
WT1
Nuclear
Affinity chromatography
BASP1
Histone
Promoter


Unexpected mutations were expected and unrelated to CRISPR-Cas9 activity.

Abstract: The scientific journal Nature Methods have just retracted a publication that reported numerous unexpected mutations after a CRISPR-Cas9 experiment based on collecting whole genome sequencing information from one control and two experimental genome edited mice. In the intervening 10 months since publication the data presented have been strongly contested and criticized by the scientific and biotech communities, through publications, open science channels and social networks. The criticism focused on the animal used as control, which was derived from the same mouse strain as the experimental individuals but from an unrelated sub-colony, hence control and experimental mice were genetically divergent. The most plausible explanation for the vast majority of the reported unexpected mutations were the expected underlying genetic polymorphisms that normally accumulate in two different colonies of the same mouse strain which occur as a result of spontaneous mutations and genetic drift. Therefore, the reported mutations were most likely not related to CRISPR-Cas9 activity.

CRISPR
Cas9
Gene therapy
Genome editing applications
Off target mutations
Safety


Approved and experimental countermeasures against pestiviral diseases: Bovine viral diarrhea, classical swine fever and border disease.

Abstract: The pestiviruses, bovine viral diarrhea virus (BVDV), classical swine fever (CSFV) and border disease virus, are important livestock pathogens in many countries, but current vaccines do not completely prevent the spread of infection. Control of pestiviral diseases is especially difficult due to the constant viremia and viral shedding of persistently infected (PI) animals, which must be identified and eliminated to prevent disease transmission. Existing vaccines are limited by the delay between vaccination and the onset of protection, the difficulty of differentiating serologically between vaccinated and naturally infected animals and the need for broad vaccine cross-protection against diverse virus strains. Antiviral therapy could potentially supplement vaccination by providing immediate protection in the case of an outbreak. Numerous compounds with in vitro antiviral activity against BVDV have been identified through its role as a surrogate for hepatitis C virus. Fewer drugs active against CSFV have been identified, but many compounds that are effective against BVDV will likely inhibit CSFV, given their similar genomic sequences. While in vitro research has been promising, the paucity of efficacy studies in animals has hindered the commercial development of effective antiviral drugs against the pestiviruses. In this article, we summarize the clinical syndromes and routes of transmission of BVD, CSF and border disease, discuss currently approved vaccines, review efforts to develop antiviral therapies for use in outbreak control and suggest promising directions for future research.

Newcomer|Benjamin W|BW|
Givens|M Daniel|MD|

D000818:Animals
D000998:Antiviral Agents
D001882:Border Disease
D002417:Cattle
D002418:Cattle Diseases
D006691:Classical Swine Fever
D006692:Classical Swine Fever Virus
D001908:Diarrhea Viruses, Bovine Viral
D013552:Swine
D014765:Viral Vaccines

Bovine viral diarrhea
Classical swine fever
Border disease
Vaccine
Antiviral therapy
Pestivirus


Detection of Bisphenol A in dental wastewater after grinding of dental resin composites.

Abstract:
OBJECTIVES
This study evaluated the release of bisphenol A (BPA) in wastewater after grinding of resin composites and tested three filtration materials.

METHODS
Three resin composites (Ceram X, Filtek Supreme XTE and Core-X flow) were used. Samples (5mm×2mm, n=10) were prepared using a metal mold and were polymerized for 20s according to manufacturers' instructions. A dental unit was disconnected from wastewater circulation and composite samples were ground under standardized procedures (200,000rpm; 90s). Wastewater was collected in glass bottles. Water samples were collected as control by performing the same procedure without grinding resin composite. All samples were stored at 7°C for 6 months to simulate storage. Then they were analyzed by HPLC-FLD. Three filtration materials (Zeosorb, Katalox Light and Catalytic Carbon) were used for water treatment to remove BPA. BPA-water solutions were prepared; corresponding to the highest amount released by the resin composites. These solutions were analyzed before and after filtration by HPLC-FLD and their efficacy (%) was calculated.

RESULTS
BPA was detected in all composite solutions: Ceram X and Filtek Supreme XTE showed similar findings (p>0.05) which were significantly higher than the control (p<0.001) and Core-X flow (p=0.001). The efficacy of the filtration materials was: Katalox Light (5.09%)<Zeosorb (7.91%)<Catalytic Carbon (99.38%). Only Catalytic Carbon caused a clinically significant reduction of BPA (p<0.05).

SIGNIFICANCE
BPA can be released in wastewater during dental procedures. This release seems to be material dependent. Among the filtration methods tested, Catalytic carbon seems to be effective for BPA reduction in water.

Polydorou|Olga|O|
Schmidt|Ole-Christian|OC|
Spraul|Mathias|M|
Vach|Kirstin|K|
Schulz|Simon Daniel|SD|
König|Armin|A|
Hellwig|Elmar|E|
Gminski|Richard|R|

D001559:Benzhydryl Compounds
D003188:Composite Resins
D003764:Dental Materials
D008422:Materials Testing
D010636:Phenols
D062065:Waste Water

Bisphenol A
Dental wastewater
Resin composites
Catalytic carbon
Filtration methods
HPLC


A 3D MoS₂/Graphene Microsphere Coated Separator for Excellent Performance Li-S Batteries.

Abstract: Lithium-sulfur (Li-S) batteries are the most prospective energy storage devices. Nevertheless, the poor conductivity of sulfur and the shuttling phenomenon of polysulfides hinder its application. In this paper, flower-like MoS₂/graphene nanocomposite is prepared and deposited on a multi-functional separator to enhance the electrochemical behavior of Li-S batteries. The results demonstrated that the MoS₂/graphene-coated separator is contributing to inhibit the shuttling phenomenon of polysulfides and improve the integrity of sulfur electrode. The initial discharge capacity of the battery using MoS₂/graphene-coated separator at 0.2 C was up to 1516 mAh g-1. After 100 cycles, a reversible capacity of 880 mAh g-1 and a coulombic efficiency of 98.7% were obtained. The improved electrochemical behavior can be due to the nanostructure and Mo-S bond of the MoS₂/graphene composite, which can combine physical shielding and chemisorption to prohibit the shuttle effect of polysulfides. The results prove that the MoS₂/graphene-coated separator has the potential for feasible application in Li-S batteries to enhance their electrochemical performance.

Yang|Shuang|S| Zhang|Junfan|J| Tan|Taizhe|T| Zhao|Yan|Y| Liu|Ning|N| Li|Haipeng|H|

Li-S battery
shuttle effect
MoS2/graphene-coated separator


Vascular Disorders of the Cerebellum in Children.

Abstract: Key differences exist in the epidemiology, pathophysiology, and clinical presentation of vascular lesions of the cerebellum in children versus adults. An understanding of these differences and an appreciation of the distinct imaging features of these lesions aid in distinguishing normal vascular variations from pathology, in predicting lesion etiology, and in directing effective treatment strategies. This paper reviews the embryogenesis of the normal vascular system of the cerebellum and brainstem and then discusses the clinical and imaging features of the common vascular lesions affecting these structures in the pediatric population.

De Leacy|Reade A|RA|
Berenstein|Alejandro|A|
Naidich|Thomas P|TP|

Cerebellum
Capillary telangiectasia
Cavernous malformations
Cerebral arteriovenous fistulae
Cerebral arteriovenous malformations
Cerebral vascular embryology
Developmental venous anomalies
Intracranial arterial aneurysms


Toxic chromium treatment induce amino-assisted electrostatic adsorption for the synthesis of highly dispersed chromium catalyst.

Abstract: Removal of toxic Cr (VI) from aqueous solutions using silicon-based adsorbents has been widely investigated. Meanwhile, contradictory between highly dispersed active Cr species and high Cr loading over commercial Cr-based catalyst was inevitable. In this work, amino-assisted electrostatic adsorption from toxic Cr (VI) treatment was developed to prepare highly dispersed Cr oxides catalysts supported on MCM-41. The Cr loading was as high as 15 wt%, and structure characters of the catalysts were well-reserved. As a result, electrostatic adsorption and subsequent complexation from negatively charged Cr (VI) species and positively charged ammonium groups made a positive contribution to the appearance of highly dispersed mono Cr species, which gave rise to improved non-oxidative propane dehydrogenation (PDH) activity. In contrast, the agglomeration of Cr species and lower PDH activity were observed on the sample synthesized using the traditional wet impregnation method. Besides, the transformation of Cr (VI) to active Cr (III) sites over the catalyst was proved by the designed in-situ H2-TPR, ex-situ UV-vis and Raman spectra results. This procedure reflects a new avenue of green chemistry, which can recycle waste Cr adsorbents as efficient PDH catalysts.

Yang|Shuang|S| He|Dedong|D| Zhang|Liming|L| Zhang|Yaliu|Y| Lu|Jichang|J| Luo|Yongming|Y|

Toxic chromium
Electrostatic adsorption
Propane dehydrogenation
High dispersion
Mono Cr (VI)


siRNA-knockdown of ADAMTS-13 modulates endothelial cell angiogenesis.

Abstract: ADAMTS-13, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13, is a zinc-containing metalloprotease that cleaves von Willebrand factor (vWf). Previous publications by our laboratory have shown that ADAMTS-13 may also be involved in angiogenesis. For this study, we report the successful transient knockdown of endogenous ADAMTS-13 in human umbilical vein endothelial cells (HUVEC) via siRNA and the effects of reduced endogenous ADAMTS-13 on HUVEC angiogenesis functions. 15nM of ADAMTS-13 siRNA reduced HUVEC ADAMTS-13 protein levels by 90% after 24h incubation, whereas control siRNA did not affect endogenous ADAMTS-13 levels. Furthermore, this transfection did not affect the HUVEC endogenous protein level of ADAMTS-1, a related family member of ADAMTS-13 indicating the specificity of the siRNA. Transfection of HUVEC with 15nM of ADAMTS-13 siRNA resulted in a 21% decrease in proliferation after 24h incubation. The effects of ADAMTS-13 knockdown on migration of HUVEC across a scratch wound were also evaluated. 24h after transfection with control siRNA, there was increased cell migration across the scratch wound. This dramatic migration did not occur with ADAMTS-13 knockdown cells. Decreased protein levels of endogenous ADAMTS-13 also affected angiogenesis as measured by endothelial cell tube formation using a Matrigel matrix method. The tube lengths, sizes and junction numbers of the ADAMTS-13 knockdown cells were all significantly lower compared to control cells by about 40%. The protein level of vascular endothelial growth factor (VEGF), a well-known regulator of angiogenesis, was significantly decreased by 45% upon knockdown of ADAMTS-13. Moreover, activity of the AKT pathway, one of the VEGF angiogenesis downstream signaling pathways was down-regulated by ADAMTS-13 siRNA. These data indicate that in cultured endothelial cells, one role of endogenous ADAMTS-13 is regulation of angiogenesis, mediated through VEGF and AKT signaling pathway. Overall, our data suggest an additional model of endogenous ADAMTS-13 functionality, beyond that of cleaving von Willebrand factor.

Tang|Huiyuan|H|
Lee|Manfai|M|
Kim|Eun Ho|EH|
Bishop|Daniel|D|
Rodgers|George M|GM|

D061307:Human Umbilical Vein Endothelial Cells

D042461:Vascular Endothelial Growth Factor A

ADAMTS-13
Endothelial cell
Angiogenesis
Von Willebrand factor
siRNA
Vascular endothelial growth factor


Post Splenectomy Outcome in β-Thalassemia.

Abstract:
OBJECTIVES
To evaluate changes in annual blood transfusion requirements and complications after splenectomy in patients with β-thalassemia.

METHODS
Forty post-splenectomy β-thalassemic patients aged 8-33 y, receiving regular blood transfusions and chelation therapy were included and non transfusion dependant patients were excluded from this retrospective cross-sectional study. Details about their surgery, transfusion requirements, and platelet levels were recorded on a standard proforma. All patients underwent a B-mode and color-coded duplex sonography of the hepatoportal system during the study period.

RESULTS
The average ferritin level in the year prior to the study was 4432 mcg/L (range 480-12,200 mcg/L). The annual blood transfusion requirement in the first year and 5 y post splenectomy [mean ± SD (138.41 ± 90.38 ml/kg/y); (116 ± 41.44 ml/kg/y)] were significantly different from requirements before splenectomy [(mean ± SD) 294.85 ± 226 ml/kg/y; p value <0.001]. There was a significant rise in platelet counts within 24 h post splenectomy with a mean rise of 4,51,000/mm(3) (p value < 0.001). During the follow up period, infections were noted in 50 % of patients, with malaria (18.75 %) being the most common. Doppler study of the portal system in one case showed portal vein thrombosis.

CONCLUSIONS
A significant sustained fall in annual blood transfusion requirement and a rise in platelet counts occurred post-splenectomy. Increase in annual blood transfusion requirement should be investigated to find the cause.

Merchant|Rashid H|RH|
Shah|Ami R|AR|
Ahmad|Javed|J|
Karnik|Alka|A|
Rai|Nooralam|N|

Transfusion requirements
Complications
Post-splenectomy
Splenunculi
Thalassemia


Continuing increase of tick bites and Lyme disease between 1994 and 2009.

Abstract:
BACKGROUND
Nationwide cross-sectional retrospective studies have shown a continuous increase in general practitioner (GP) consultations for tick bites and diagnoses of erythema migrans between 1994 and 2005 in the Netherlands. In this paper, we report incidence estimates for GP consultations for tick bites and erythema migrans diagnoses in 2009, and we compare the observed increase in GP consultations to reports of tick bites in two retrospective cross-sectional surveys of the general population.

METHODS
All GPs in the Netherlands were asked to complete a postal questionnaire on the number of consultations for tick bites and erythema migrans diagnoses in 2009, and the size of their practice populations. To investigate how the incidence of GP consultation rates for tick bites and erythema migrans relate to the incidence of tick bites in the general population, questionnaire data on tick bites were analyzed from two large population surveys conducted to evaluate the national immunization program in 1995/1996 and 2006/2007.

RESULTS
The 2009 GP survey revealed a further increase, to 564 tick bite consultations per 100,000 inhabitants, and 134 erythema migrans diagnoses per 100,000 inhabitants of the Netherlands. The two population surveys from 1995/1996 and 2006/2007 exhibited an almost twofold increase of the incidence of tick bites in the general population from 4099 per 100,000 population in 1996, to 7198 per 100,000 population in 2007. People nationwide noticed approximately 1.1 million tick bites in 2007.

CONCLUSIONS
Our observation of increases in GP consultations for tick bites and erythema migrans diagnoses between 1994 and 2009 are confirmed by the parallel increase of tick bites reported by the general population, although consultation rates slightly increased. For every sixty tick bites in the general population in 2007, we observed one GP consult for erythema migrans. The increase in tick bites poses a progressive threat to public health.

Hofhuis|Agnetha|A|
Harms|Margriet|M|
van den Wijngaard|Cees|C|
Sprong|Hein|H|
van Pelt|Wilfrid|W|

Tick bites
Erythema migrans
Incidence
General population
Lyme borreliosis


Role of Mean Platelet Volume in the Prognosis of Gallbladder Carcinoma: A Tertiary Centre Experience.

Abstract: Mean platelet volume (MPV) is an inflammatory marker indicative of platelet activation. There are several studies that suggest an association between the neoplastic process and cancer metastasis. We performed a retrospective analysis to investigate the role of MPV as a prognostic informative marker in gallbladder cancer. This study included 73 patients who underwent treatment for gallbladder cancer with curative or palliative intent. MPV was obtained and statistically analysed to investigate the association between the nodal status (N), the overall stage as per the American Joint Committee on Cancer (AJCC) staging system, perineural invasion, and differentiation of the tumor. The statistical analysis was done using SPSS Statistics, version 23 (IBM Corp., Armonk, NY). We found that the MPV values were significantly high in node-positive cases (OR = 3.623, 95% CI = 7.778-1.687, p value = -0.0001), cases in the advanced stage (OR = 3.623, 95% CI = 7.778-1.687, p value = 0.0001), cases with perineural invasion (OR = 3.396, 95% CI = 8.319-1.387, p value = -0.0001), and poor differentiation (OR = 2.327, 95% CI = 4.651-1.164, p value = -0.002 ). MPV is an inexpensive and convenient inflammatory marker that correlates with nodal positivity in the staging and prognostication of gallbladder cancer. This marker can be used to ascertain the risk status of gallbladder cancer.

Bv|Prakash|P|
Anwar|Ali Z|AZ|
Harsha|Raghavendra|R|
Arakeri|Praveen R|PR|
Jonnada|Pavan|P|

mean platelet volume
overall stage
diagnosis
gall bladder cancer
lymph node status


Subungual exostosis recurrence in a 16-year-old athletic male.

Abstract: Subungual exostosis is a painful, benign bony outgrowth projecting from the distal phalanx of the toes. The present case consists of a 16-year-old male that presented to the primary clinic with a single circumscribed painful lesion underneath the nail of the first phalanx of the left foot that recurred after surgical extraction.

subungual exostosis
recurrence
dermatology
nail deformity


Crystal structure and computational study of 3,4-dihy-droxy-3-hy-droxy-methyl-9-methyl-6-methyl-idene-3a,4,5,6,6a,9,9a,9b-octa-hydro-azuleno[4,5-b]furan-2,8(3H,7H)-dione.

Abstract: In the mol-ecule of title compound, C15H20O6, also known as cynarinin A, the cyclo-pentane ring having twist conformation and a γ-lactone ring assuming an envelope conformation are trans- and cis-fused, respectively, to a cyclo-heptane ring adopting a twist-chair conformation. In the crystal, O-H⋯O hydrogen bonds link neighbouring mol-ecules, forming a three-dimensional network. Theoretical calculations of the mol-ecular structure using the CNDO approximation and MOPAC PM3 geometry optimization are in satisfactory agreement with the results of the X-ray structure analysis.

Çelik|Ísmail|Í| Akkurt|Mehmet|M| Akşit|Hüseyin|H| Erenler|Ramazan|R| García-Granda|Santiago|S|

crystal structure
cynarinin A
CNDO
PM3
Centaurea polypodiifolia
HOMO
LUMO
theoretical investigation


Deep/mixed cerebral microbleeds are associated with cognitive dysfunction through thalamocortical connectivity disruption: The Taizhou Imaging Study.

Abstract:
BACKGROUND
Cerebral microbleeds (CMBs) are considered to be risk factors for cognitive dysfunction. The specific pathology and clinical manifestations of CMBs are different based on their locations. We investigated the association between CMBs at different locations and cognitive dysfunction and explored the potential underlying pathways in a rural Han Chinese population.

METHODS
We used baseline data from 562 community-dwelling adults (55-65 years old) in the Taizhou Imaging Study between 2013 and 2015. All individuals underwent multimodal brain magnetic resonance imaging (MRI) and 444 subjects completed neuropsychological tests: the Mini-Mental Status Examination and the Montreal Cognitive Assessment. Multinomial logistic regression was used to estimate the association between CMBs and cognitive dysfunction. The volume of brain regions and white matter microstructure were analyzed using Freesurfer and tract-based spatial statistics, respectively.

RESULTS
CMBs were detected in 104 individuals (18.5%) in our study. Multinomial logistic regression found deep/mixed CMBs were associated with global cognitive dysfunction (OR 3.52; 95% CI 1.21 to 10.26), whereas lobar CMBs (OR 1.76; 95% CI 0.56 to 5.53) were not. Quantification of multimodal brain MRI showed that deep/mixed CMBs were accompanied by decreased thalamic volume and loss of fractional anisotropy of bilateral anterior thalamic radiations.

CONCLUSION
Deep/mixed CMBs were associated with cognitive dysfunction in this Chinese cross-sectional study. Disruption of thalamocortical connectivity might be a potential pathway underlying this relationship.

Wang|Yingzhe|Y| Jiang|Yanfeng|Y| Suo|Chen|C| Yuan|Ziyu|Z| Xu|Kelin|K| Yang|Qi|Q| Tang|Weijun|W| Zhang|Kexun|K| Zhu|Zhen|Z| Tian|Weizhong|W| Fan|Min|M| Li|Shuyuan|S| Ye|Weimin|W| Dong|Qiang|Q| Jin|Li|L| Cui|Mei|M| Chen|Xingdong|X|

Cerebral microbleeds
Cognitive impairment
Multimodal imaging


Reduced primary care respiratory infection visits following pregnancy and infancy vitamin D supplementation: a randomised controlled trial.

Abstract:
AIM
To determine whether vitamin D supplementation reduces primary care visits for acute respiratory infection (ARI).

METHODS
A randomised, double-blind, placebo-controlled trial was conducted in New Zealand and powered to determine the vitamin D dose needed to achieve normal vitamin D status during infancy. Healthy pregnant women, from 27 weeks' gestation to birth, and their infants, from birth to age 6 months, were assigned to placebo or one of the two dosages of daily oral vitamin D3 . Woman/infant pairs were randomised to placebo/placebo, 1000 IU/400 IU or 2000 IU/800 IU. For this ad hoc analysis, the primary care records of enrolled children were audited to age 18 months.

RESULTS
Two hundred and sixty pregnant women were randomised to placebo (n = 87), lower-dose (n = 87) or higher-dose (n = 86) vitamin D3 . In comparison with the placebo group (99%), the proportion of children making any ARI visits was smaller in the higher-dose (87%, p = 0.004), but not the lower-dose vitamin D3 group (95%, p = 0.17). The median number of ARI visits/child was less in the higher-dose vitamin D3 group from age 6-18 months (placebo 4, lower dose 3, higher dose 2.5; p = 0.048 for higher-dose vitamin D3 vs. placebo).

CONCLUSION
Vitamin D3 supplementation during pregnancy and infancy reduces primary care visits for ARI during early childhood.

Grant|Cameron C|CC|
Kaur|Suhina|S|
Waymouth|Ellen|E|
Mitchell|Edwin A|EA|
Scragg|Robert|R|
Ekeroma|Alec|A|
Stewart|Alistair|A|
Crane|Julian|J|
Trenholme|Adrian|A|
Camargo|Carlos A|CA|

Pregnancy
Vitamin D
Child
Clinical trial
Respiratory tract infections


Rheological Characterization of Solids Phase in Biomass Processes of Disc-Stack Centrifuges.

Abstract: Rheological characterization of the solids phase in bio-industry disc-stack centrifuges is considered. Three discriminatory properties of the solids phase are investigated, namely, the particle settling velocity, the angle of repose, and the solids phase viscosity. The solids phase produced in disc-stack centrifuges in the food or biopharmaceutical industry possesses both liquid-like and solid-like properties which can be quantified by means of these test methods. The resulting rheological characterization can be used for diagnostic purposes in the selection process of industrial centrifuges and for optimization of centrifuge solids handling in biomass processing of suspension systems.

Biomass processing
Angle of repose
Solids phase viscosity
Centrifuge solids rheology
Squeeze flow


From Thermogelling Hydrogels toward Functional Bioinks: Controlled Modification and Cytocompatible Crosslinking.

Abstract: Hydrogels are key components in bioink formulations to ensure printability and stability in biofabrication. In this study, a well-known Diels-Alder two-step post-polymerization modification approach is introduced into thermogelling diblock copolymers, comprising poly(2-methyl-2-oxazoline) and thermoresponsive poly(2-n-propyl-2-oxazine). The diblock copolymers are partially hydrolyzed and subsequently modified by acid/amine coupling with furan and maleimide moieties. While the thermogelling and shear-thinning properties allow excellent printability, trigger-less cell-friendly Diels-Alder click-chemistry yields long-term shape-fidelity. The introduced platform enables easy incorporation of cell-binding moieties (RGD-peptide) for cellular interaction. The hydrogel is functionalized with RGD-peptides using thiol-maleimide chemistry and cell proliferation as well as morphology of fibroblasts seeded on top of the hydrogels confirm the cell adhesion facilitated by the peptides. Finally, bioink formulations are tested for biocompatibility by incorporating fibroblasts homogenously inside the polymer solution pre-printing. After the printing and crosslinking process good cytocompatibility is confirmed. The established bioink system combines a two-step approach by physical precursor gelation followed by an additional chemical stabilization, offering a broad versatility for further biomechanical adaptation or bioresponsive peptide modification.

hydrogels
biofabrication
bioprinting
chemical crosslinking


Features of inflammatory heart reactions following mRNA COVID-19 vaccination at a global level.

Abstract: Myocarditis and pericarditis may constitute adverse reactions of mRNA COVID-19 vaccines. This study aimed to document these reactions and to assess the association with patient sex and age. This is as an observational retrospective study using a case-non-case design (also called disproportionality study) on inflammatory heart reactions reported with mRNA COVID-19 vaccines within the WHO global safety database (VigiBase), up to June 30th 2021. Results are expressed using reporting odds-ratios (ROR) and their 95% confidence interval (95%CI). Of 716,576 reports related to mRNA COVID-19 vaccines, 2277 were cases of inflammatory heart reactions, including 1241 (55%) myocarditis and 851 (37%) pericarditis. The main age group was 18-29 years (704, 31%), and mostly males (1555, 68%). Pericarditis onset was delayed compared to myocarditis with a median time to onset of 8 [3-21] vs. 3 [2-6] days, respectively (p=0.001). Regarding myocarditis, an important disproportionate reporting was observed in adolescents (ROR, 22.3 [19.2-25.9]) and in 18-29 years old (ROR, 6.6 [5.9-7.5]) compared to older patients, as well as in males (ROR, 9.4 [8.3-10.6]). Reporting rate of myocarditis was increased in young adults and adolescents. Inflammatory heart reactions may rarely occur shortly following mRNA COVID-19 vaccination. Although an important disproportionate reporting of myocarditis was observed among adolescents and young adults, particularly in males, reporting rates support a very rare risk, that does not seem to compromise the largely positive benefit-risk balance of these vaccines. Furthermore, this study confirmed the value of disproportionality analyses for estimation of relative risks among subgroups of patients.

Chouchana|Laurent|L|
Blet|Alice|A|
Al-Khalaf|Mohammad|M|
Kafil|Tahir S|TS|
Nair|Girish|G|
Robblee|James|J|
Drici|Milou-Daniel|MD|
Valnet-Rabier|Marie-Blanche|MB|
Micallef|Joëlle|J|
Salvo|Francesco|F|
Treluyer|Jean-Marc|JM|
Liu|Peter P|PP|

COVID-19
myocarditis
pericarditis
adverse drug reactions
mRNA vaccines
pharmacovigilance


Phenolic Acids-Rich Fractions from Agaricus bitorguis (Quél.) Sacc. Chaidam ZJU-CDMA-12 Mycelia Modulate Hypoxic Stress on Hypoxia-Damaged PC12 Cells.

Abstract: Hypoxia is a common pathological process in various clinical diseases. However, there is still a lack of effective anti-hypoxia active substances. Agaricus bitorguis (Quél.) Sacc Chaidam (ABSC) is a rare wild edible macrofungus that grows underground at high altitudes. Herein, intracellular phenolic acids-rich fractions (IPA) were extracted from ABSC ZJU-CDMA-12, and the structural characterization and anti-hypoxia activity of IPA on PC12 cells were elucidated as well. The results of HPLC-Q-TOF-MS illustrated that five kinds of IPA were isolated from ABSC, including (-)-epicatechin gallate, arabelline, yunnaneic acid D, 2'-O-p-hydroxybenzoyl-6'-O-trans-caffeoylgardoside,4'-O-methylgallocatechin-(4->8)-4'-O-methylepigallocatechin. IPA extracted from ABSC proved to show anti-hypoxia activity on hypoxia-damaged PC12 cells. Hypoxia enhanced reactive oxygen species (ROS) generation and reduced the mitochondrial membrane potential (ΔΨm) in PC12 cells, resulting in the inhibition of survival and induction of apoptosis in PC12 cells. Measurements of 100 μg/mL and 250 μg/mL IPA could significantly reduce hypoxia-induced damage in PC12 cells by decreasing overproduced intracellular ROS, improving ΔΨm, and reducing cell apoptosis rate. Our findings indicated that the IPA from ABSC potentially could be used as novel bioactive components applied to anti-hypoxia functional foods or medicines.

Lu|Hongyun|H| Jiao|Zhihua|Z| Jiao|Yingchun|Y| Wang|Wei|W| Chen|Qihe|Q|0000-0003-3862-4356

Agaricus bitorquis (QuéL.) Sacc. Chaidam