Patent foramen ovale closure, antiplatelet therapy or anticoagulation in patients with patent foramen ovale and cryptogenic stroke: a systematic review and network meta-analysis incorporating complementary external evidence.

Abstract:
OBJECTIVE
To examine the relative impact of three management options in patients aged <60 years with cryptogenic stroke and a patent foramen ovale (PFO): PFO closure plus antiplatelet therapy, antiplatelet therapy alone and anticoagulation alone.

DESIGN
Systematic review and network meta-analysis (NMA) supported by complementary external evidence.

DATA SOURCES
Medline, EMBASE and Cochrane CENTRAL.

STUDY SELECTION
Randomised controlled trials (RCTs) addressing PFO closure and/or medical therapies in patients with PFO and cryptogenic stroke.

REVIEW METHODS
We conducted an NMA complemented with external evidence and rated certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.

RESULTS
Ten RCTs in eight studies proved eligible (n=4416). Seven RCTs (n=3913) addressed PFO closure versus medical therapy. Of these, three (n=1257) addressed PFO closure versus antiplatelet therapy, three (n=2303) addressed PFO closure versus mixed antiplatelet and anticoagulation therapies and one (n=353) addressed PFO closure versus anticoagulation. The remaining three RCTs (n=503) addressed anticoagulant versus antiplatelet therapy. PFO closure versus antiplatelet therapy probably results in substantial reduction in ischaemic stroke recurrence (risk difference per 1000 patients over 5 years (RD): -87, 95% credible interval (CrI) -100 to -33; moderate certainty). Compared with anticoagulation, PFO closure may confer little or no difference in ischaemic stroke recurrence (low certainty) but probably has a lower risk of major bleeding (RD -20, 95% CrI -27 to -2, moderate certainty). Relative to either medical therapy, PFO closure probably increases the risk of persistent atrial fibrillation (RD 18, 95% CI +5 to +56, moderate certainty) and device-related adverse events (RD +36, 95% CI +23 to +50, high certainty). Anticoagulation, compared with antiplatelet therapy, may reduce the risk of ischaemic stroke recurrence (RD -71, 95% CrI -100 to +17, low certainty), but probably increases the risk of major bleeding (RD +12, 95% CrI -5 to +65, moderate certainty).

CONCLUSIONS
In patients aged <60 years, PFO closure probably confers an important reduction in ischaemic stroke recurrence compared with antiplatelet therapy alone but may make no difference compared with anticoagulation. PFO closure incurs a risk of persistent atrial fibrillation and device-related adverse events. Compared with alternatives, anticoagulation probably increases major bleeding.

PROSPERO REGISTRATION NUMBER
CRD42017081567.

Mir|Hassan|H|0000-0002-7486-8123
Siemieniuk|Reed Alexander C|RAC|
Ge|Long|L|
Foroutan|Farid|F|
Fralick|Michael|M|
Syed|Talha|T|
Lopes|Luciane Cruz|LC|
Kuijpers|Ton|T|
Mas|Jean-Louis|JL|
Vandvik|Per O|PO|
Agoritsas|Thomas|T|0000-0002-6182-9969
Guyatt|Gordon H|GH|

D000925:Anticoagulants
D001281:Atrial Fibrillation
D002545:Brain Ischemia
D006348:Cardiac Surgical Procedures
D003131:Combined Modality Therapy
D054092:Foramen Ovale, Patent
D006801:Humans
D000071076:Network Meta-Analysis
D010975:Platelet Aggregation Inhibitors
D011183:Postoperative Complications
D012008:Recurrence
D055502:Secondary Prevention
D020521:Stroke

patent foramen ovale
antiplatelet
anticoagulation
cryptogenic stroke
pfo closure


Lymphangiography and Lymphatic Embolization for the Treatment of Refractory Chylous Ascites.

Abstract:
PURPOSE
Assess the effectiveness of conventional lymphangiography, MR lymphangiography, and lymphatic embolization for the diagnosis and treatment of refractory chylous ascites.

MATERIALS AND METHODS
A retrospective review of 31 patients (M/F:16/15, average age 52) who presented for the management of refractory chylous ascites was conducted to assess the diagnostic value of conventional and MR lymphangiography and outcome of lymphatic embolization.

RESULTS
Of the total 31 patients, 25 presented with chylous ascites secondary to iatrogenic trauma and six patients with a non-traumatic etiology. All patients underwent conventional lymphangiography and nine underwent MR lymphangiogram. The lymphatic leak was visualized in 17/31 (55%) of the patients (15 of which were traumatic) and in 7/9 MR lymphangiograms (six traumatic and one non-traumatic). Embolization with n-BCA glue and/or coils of the leak was performed in 11 of the 17 patients whose leak was identified (65%) with resolution of chylous ascites in 9/11 (82%) patients. Lymphangiogram alone was curative in 7/20 (35%) patients. Overall, 16/31 patients (52%) had clinical resolution of ascites. Ascites resolved in 13/17 (76%) patients in whom the site of leak could be identified compared to 3/14 (21%) of patients in whom the site of leak could not be identified (p = 0.0038).

CONCLUSIONS
Lymphangiography and embolization can be used to treat chylous ascites. Identification of the site of leak is associated with significantly greater rate of clinical success compared to those whose site could not be identified.

Lymphangiography
Embolization
Chylous ascites


Influenza vaccination in older people with diabetes and their household contacts.

Abstract:
BACKGROUND
People with diabetes are at a higher risk of influenza infections and severe complications. The vaccination of close contacts could offer indirect protection to people with diabetes; this is known as "herd immunity." The aim of this study is to investigate the vaccination rates of people with diabetes and their household contacts in Hong Kong.

RESEARCH DESIGN AND METHODS
Face-to-face interviews with 158 patients diagnosed with Type 2 diabetes and aged ⩾65years were conducted in clinics. Telephone interviews were then conducted with 281 adult household contacts.

RESULTS
Seasonal influenza vaccination rates were 54.5% and 27.4%, in people with diabetes and their contacts, respectively. The vaccination status of patients was not significantly associated with the vaccination of their household contacts (p=0.073). Among household contacts, children or the elderly, the partners or couples of patients, and those with more hours of daily contact, or with chronic conditions, were associated with higher vaccination rates. However, only age remained significant after adjusting for confounding factors in logistic regression models.

CONCLUSIONS
The low vaccination rates of people with diabetes and their close contacts highlight the need to promote vaccination in susceptible populations and to educate the public about herd immunity.

Yang|Lin|L|
Nan|Hairong|H|
Liang|Jun|J|
Chan|Yin Hang|YH|
Chan|Laam|L|
Sum|Rita Wing Man|RW|
Kwan|Yee Mei|YM|
Zhou|Feifei|F|
Meng|Huaiqing|H|
Suen|Lorna Kwai Ping|LK|

D007722:Health Knowledge, Attitudes, Practice

Influenza
Vaccine
Diabetes
Household
Herd immunity


Gamma-index method sensitivity for gauging plan delivery accuracy of volumetric modulated arc therapy.

Abstract:
PURPOSE
The aim of this study was to investigate the sensitivity of the gamma-index method according to various gamma criteria for volumetric modulated arc therapy (VMAT).

METHODS
Twenty head and neck (HN) and twenty prostate VMAT plans were retrospectively selected for this study. Both global and local 2D gamma evaluations were performed with criteria of 3%/3 mm, 2%/2 mm, 1%/2 mm and 2%/1 mm. In this study, the global and local gamma-index calculated the differences in doses relative to the maximum dose and the dose at the current measurement point, respectively. Using log files acquired during delivery, the differences in parameters at every control point between the VMAT plans and the log files were acquired. The differences in dose-volumetric parameters between reconstructed VMAT plans using the log files and the original VMAT plans were calculated. The Spearman's rank correlation coefficients (rs) were calculated between the passing rates and those differences.

RESULTS
Considerable correlations with statistical significances were observed between global 1%/2 mm, local 1%/2 mm and local 2%/1 mm and the MLC position differences (rs = -0.712, -0.628 and -0.581). The numbers of rs values with statistical significance between the passing rates and the changes in dose-volumetric parameters were largest in global 2%/2 mm (n = 16), global 2%/1 mm (n = 15) and local 2%/1 mm (n = 13) criteria.

CONCLUSION
Local gamma-index method with 2%/1 mm generally showed higher sensitivity to detect deviations between a VMAT plan and the delivery of the VMAT plan.

Park|Jong In|JI|
Park|Jong Min|JM|
Kim|Jung-In|JI|
Park|So-Yeon|SY|
Ye|Sung-Joon|SJ|

Gamma-index method
Volumetric modulated arc therapy
Dynamic log file
Pre-treatment quality assurance


Relevance Analysis of Sustainable Development of China's Yangtze River Economic Belt Based on Spatial Structure.

Abstract: Scientifically justifiable spatial structure can not only promote the efficient use of regional resources, but can also effectively avoid "urban diseases", such as traffic congestion, housing shortage, resource scarcity, and so on. It is the "regulator" and "booster" of regional development. Firstly, this paper measures the spatial structure of the Yangtze River Economic Belt from the four dimensions of scale distribution, central structure, spatial connection, and compactness: Gini coefficient of urban scale, urban primacy, regional economic linkage strength, and spatial compactness. Secondly, the optimized Super-Slack Based Measure-Undesirable model is used to evaluate the sustainable development status of the Yangtze River Economic Belt. Finally, a sustainable development correlation analysis model based on regional spatial structure is constructed. Based on the overall perspective of the Yangtze River Economic Belt and the individual perspective of 11 provinces and cities, the relationship between the spatial structure of the Yangtze River Economic Belt and sustainable development is analyzed. It is found that the impact of the four spatial structure indicators on the sustainable development level of the Yangtze River Economic Zone is relatively stable in five different periods. The ranking results are as follows: Gini coefficient of urban scale > urban primacy > regional economic linkage strength > spatial compactness.

Tang|Decai|D|
Li|Zhijiang|Z|0000-0003-4781-205X
Bethel|Brandon J|BJ|

relevance analysis
sustainable development
China’s Yangtze River Economic Belt
space structure


Suspended animation: the past, present and future of major cardiothoracic trauma.

Abstract: About 50% of the trauma victims die at the scene mostly because of exsanguinating haemorrhage. Most trials of resuscitation fail in face of the ongoing bleeding. Ongoing research/studies to save these victims by inducing rapid hypothermia using cardiopulmonary bypass as an emergency initial measure along with delayed resuscitation show improved outcomes. A comprehensive review of this research and analysis of studies showed that rapid induction of hypothermia within 5 min of cardiac arrest is associated with better survival and improved neurological outcome. This led us to conclude that suspended animation is a lifesaving modality for the treatment of trauma victims, otherwise hurtling towards certain death. This should be integrated into regular clinical practice. The US Food and Drug Administration has given its approval for clinical trials on such an intervention.

Mohiyaddin|Syed|S|0000-0003-4315-9380
Nanjaiah|Prakash|P|
Saad|Ahmed O|AO|
Acharya|Metesh N|MN|
Khan|Tanveer A|TA|
Davies|Rhodri H|RH|
Ashraf|Saeed|S|

operative intervention of cardiothoracic trauma


Bioinformatics Analysis of the Prognostic and Biological Significance of ZDHHC-Protein Acyltransferases in Kidney Renal Clear Cell Carcinoma.

Abstract: ZDHHC-protein acyltransferases (ZDHHCs) are a family of 23 signature Asp-His-His-Cys (DHHC) domain-containing enzymes that mediate palmitoylation by covalent attachment of the 16-carbon fatty acid palmitate to thiol groups of specific cysteine residues in substrate proteins. Emerging evidence has shown abnormal expression of ZDHHCs in a variety of disease states, including cancer. Kidney renal clear cell carcinoma (KIRC) is the eighth most common type of cancer, which accounts for the majority of malignant kidney tumors. However, there are currently no effective therapeutic targets or biomarkers for clinical treatment and prognosis in KIRC. In this study, we first analyzed the expression pattern of the 23 ZDHHCs in KIRC using TCGA and GEPIA database, and found that the expression of ZDHHC2, 3, 6, 14, 15, 21, and 23 was significantly down-regulated whereas the expression of ZDHHC9, 17, 18, 19 and 20 was significantly up-regulated in KIRC patient tissues vs. normal tissues. And the expression of ZDHHC2, 3, 6, 9, 14, 15, and 21 in tumors decreased with the increase of the pathological stage of KIRC patients. Notably, KIRC patients with decreased expression of ZDHHC3, 6, 9, 14, 15, 17, 20, 21, 23 and increased expression of ZDHHC19 were significantly associated with poor prognosis. Further, we found that there was a significant correlation between ZDHHC3, 6, 9, 14, 15, 17, 19, 20, 21, 23 expressions and immune cell infiltration. Besides, high mRNA expression was the most common type of gene alteration and there was a high correlation among the expression of ZDHHC6, 17, 20 and 21. Finally, function prediction indicated that the immune or metabolic disorders or the activation of oncogenic signaling pathways caused by abnormal expression of these ZDHHCs may be important mechanisms of tumor progression and poor prognosis in patients with KIRC. Our results may provide novel insight for identifying tumor markers or molecular targets for the treatment of KIRC.

Liu|Zhuang|Z| Liu|Chang|C| Xiao|Mingming|M| Han|Yamei|Y| Zhang|Siyue|S| Xu|Bo|B|

ZDHHC-protein acyltransferases
kidney renal clear cell carcinoma
prognosis
immune cell infiltration
pathway analysis


Multiple human papillomavirus infections and type-competition in women from a clinic attendee population in China.

Abstract: To investigate the multi-infection patterns and type competition for human papillomavirus (HPV) in Chinese clinic attending women and evaluate the association between the infection status and cancer risk. Three hundred and thirty-two HPV-DNA-positive samples were genotyped for 21 HPVs and tested for 13 types of HPV neutralizing antibody using pseudoviron-based assay. Odds ratios (ORs) were calculated to evaluate the coinfection patterns for both DNA and neutralizing antibody (NAb), and the associations of HSIL+ with HPV DNA and NAb. Of the 332 HPV-DNA-positive subjects, 279 (84.0%) were detected as NAb positive. Multi-positive results were identified in 23.2% (77/332) HPV DNA tests and 60.2% (168/279) HPV NAb assays. The NAb titers for the multiple-positive samples (geometric mean 214) were significantly higher than the single-positive samples (geometric mean 114) (P < 0.01). HPV16-HPV52 was identified as a type-competition pair for both HPV DNA (OR = 0.09; 95%CI = 0.02-0.42) and NAb (OR = 0.27; 95%CI = 0.11-0.69) data. Compared to other types, HPV16 DNA was associated significantly with high risk of HSIL+ (OR = 2.57; 95%CI = 1.23-5.38). HPV16-HPV52 was identified as a potential type-competition pair, which might result in the type modulation with the implementation of the approved bi- or quadri-valent vaccines. J. Med. Virol. 88:1989-1998, 2016. © 2016 Wiley Periodicals, Inc.

Nie|Jianhui|J| Liu|Jianhua|J| Xie|Hui|H| Sun|Zhengrong|Z| Zhao|Juan|J| Chen|Qingqing|Q| Liu|Yangyang|Y| Huang|Weijin|W| Ruan|Qiang|Q| Wang|Youchun|Y|

human papillomavirus
neutralization
vaccine


Residual limb pain: An evidence-based review.

Abstract: Acquired limb loss, whether from accident or amputation, occurs with an incidence of greater than 175,000 per year in the United States. Current prevalence is estimated at greater than 1.5 million and is expected to double within 30 years. While many patients with amputations may have no significant pain or sensory issues after healing from the initial loss, one-quarter to one-half of patients may have ongoing difficulties with residual limb pain, phantom limb pain, or phantom limb sensation. This review explores the potential etiologies of those symptoms, as well as a variety of treatment options that a practitioner may consider when approaching this condition.

residual limb pain
Amputation
phantom limb pain
stump pain


Aorto-caval fistula - case report.

Abstract: Aorto-caval fistula can be associated with abdominal aortic aneurysm. The fistula can manifest with nonspecific symptoms. The rupture of abdominal aortic aneurysm is one of the leading symptoms. The symptoms and the necessity of treatment are related to these acute conditions. This article describes the case of a 78 years old man with a huge abdominal aortic aneurysm and aorto-caval fistula that was presented with a sudden onset of abdominal pain, dyspnoea, hypotension and cardiac insufficiency with an acute cor pulmonale. Urgent surgery was performed - aneurysm resection with transaortic suture of the fistula and aortic replacement using a Dacron graft. Resuscitation and defibrillation were needed during the surgery due to fibrillation cardiac arrest, which were successful. The post-operative period was complicated with a persisting consciousness disorder of the patient and persisting myocardial ischaemia, resulting in the patients death 3 weeks after the surgery. The aim of this report is to point out the severity of this condition, the various treatment options of this uncommon disease with an uncertain prognosis, and also the importance of a multidisciplinary approach, essential in the entire treatment process as well as in the primary diagnosis.

D000368:Aged
D001012:Aorta, Abdominal
D017544:Aortic Aneurysm, Abdominal
D001018:Aortic Diseases
D001019:Aortic Rupture
D001164:Arteriovenous Fistula
D006801:Humans
D008297:Male
D014682:Vena Cava, Inferior

aorto-caval fistula
open repair
stentgraft


A model for the peak-interval task based on neural oscillation-delimited states.

Abstract: Specific mechanisms underlying how the brain keeps track of time are largely unknown. Several existing computational models of timing reproduce behavioral results obtained with experimental psychophysical tasks, but only a few tackle the underlying biological mechanisms, such as the synchronized neural activity that occurs throughout brain areas. In this paper, we introduce a model for the peak-interval task based on neuronal network properties. We consider that Local Field Potential (LFP) oscillation cycles specify a sequence of states, represented as neuronal ensembles. Repeated presentation of time intervals during training reinforces the connections of specific ensembles to downstream networks - sets of neurons connected to the sequence of states. Later, during the peak-interval procedure, these downstream networks are reactivated by previously experienced neuronal ensembles, triggering behavioral responses at the learned time intervals. The model reproduces experimental response patterns from individual rats in the peak-interval procedure, satisfying relevant properties such as the Weber law. Finally, we provide a biological interpretation of the parameters of the model.

Varella|Thiago T|TT|
Reyes|Marcelo Bussotti|MB|
Caetano|Marcelo S|MS|
de Camargo|Raphael Y|RY|

Timing
Computational model
Weber law
Biological neural network
Peak-procedure
Scalar property


Preoperative preparation of a patient with grade II leg Lymphedema for his third hip replacement surgery.

Abstract:
INTRODUCTION
The treatment of lymphedema remains a challenge to modern medicine, due to the characteristics of the disease.

CASE PRESENTATION
Report on the case of a 75-year-old patient with lower limb lymphedema for treatment prior to surgery. At age 45, he made the first hip replacement surgery in the left leg. One year later he performed the same surgery on the right leg. At that time his legs had slight ankle edema mainly of the left leg and the entire left leg was affected by lymphedema. At 68 years old the patient returned to the surgeon, who indicated a third surgery to replace the left hip prosthesis. The patient was evaluated by bioimpedance, which measured the volumes of right and left legs at 5.52 and 7.24l, respectively. Five days of intensive treatment were proposed using Mechanical Lymphatic Therapy (RAGodoy®), Manual Lymphatic Therapy and compression therapy with a grosgrain stocking for 24h per day. On the fifth day, there was significant improvement in the volume (right leg 4.45l and left leg 5.57l).

DISCUSSION
In this case report intensive treatment was used to reduce the volume of leg edema prior to a surgery to replace a hip prosthesis in a patient with grade II leg lymphedema. Small positive and negative changes, which are common in the evolution of this type of case but the end result was a total reduction of the edema.

CONCLUSION
The patient underwent surgery to replace the prosthesis after total reduction of edema.

Guerreiro Godoy|Maria de Fátima|MF|
Pereira de Godoy|Livia Maria|LM|
Lopes Pinto|Renata|R|
Pereira de Godoy|Jose Maria|JM|


Anti-Multiple Myeloma Potential of Secondary Metabolites from Hibiscus sabdariffa-Part 2.

Abstract: Multiple Myeloma (MM) is an aggressive tumor causing millions of deaths every year and currently available therapies are often unsuccessful or correlated with severe side effects. In our previous work we demonstrated that the Hibiscus sabdariffa hydroalcoholic extract inhibits the growth of the MM cell line and we isolated two metabolites responsible for the activity: Hib-ester and Hib-carbaldehyde. Herein we report their interaction with proteasome, one of the main targets in the fight against MM. The molecular modelling study outlined a good interaction of both compounds with the target and these results prompted us to investigate their potential to inhibit proteasome. Metabolites were then isolated from the calyces and an extract with a high content of Hib-ester and Hib-carbaldehyde was prepared. An anticancer profile was drawn, evaluating apoptosis, autophagy and proteasome inhibition, with the anticancer properties being mainly attributed to the Hib-ester and Hib-carbaldehyde, while the proteasome inhibition of the extract could also be ascribed to the presence of anthocyanins, a class of secondary metabolites already known for their proteasome inhibitory activity.

multiple myeloma
Hibiscus sabdariffa
Hib-ester
Hib-carbaldehyde
proteasome
anthocyanins
diet supplement
docking studies


The complete mitochondrial genome of Scorpiops tibetanus (Scorpionida; Euscorpiidae Laurie).

Abstract: This study is the first to sequence and analyze the mitochondrial genome of Scorpiops tibetanus . The results showed that the total length of mitochondrial genome of Scorpiops tibetanus was 14,825 bp, including 13 protein-coding genes, 22 tRNAs, 2 rRNAs, and 1 control region. According to the complete mitochondrial genome, the phylogenetic tree was established by the Scorpiops tibetanus and six closely related species. Phylogenetic tree analysis showed that the Scorpiops tibetanus is sister species to Heterometrus longimanus. This study provides theoretical references for further exploring the genetic diversity and phylogeny of scorpion.

mitochondrial genome
Scorpiops tibetanus
phylogenetic analysis


Is Social Categorization the Missing Link Between Weak Central Coherence and Mental State Inference Abilities in Autism? Preliminary Evidence from a General Population Sample.

Abstract: We explore the relationship between the 'theory of mind' (ToM) and 'central coherence' difficulties of autism. We introduce covariation between hierarchically-embedded categories and social information--at the local level, the global level, or at both levels simultaneously--within a category confusion task. We then ask participants to infer the mental state of novel category members, and measure participants' autism-spectrum quotient (AQ). Results reveal a positive relationship between AQ and the degree of local/global social categorization, which in turn predicts the pattern of mental state inferences. These results provide preliminary evidence for a causal relationship between central coherence and ToM abilities. Implications with regard to ToM processes, social categorization, intervention, and the development of a unified account of autism are discussed.

Skorich|Daniel P|DP|
May|Adrienne R|AR|
Talipski|Louisa A|LA|
Hall|Marnie H|MH|
Dolstra|Anita J|AJ|
Gash|Tahlia B|TB|
Gunningham|Beth H|BH|

Social categorization
Categorization
Weak central coherence
Autism
Theory of mind
Self-categorization


Point-of-care ultrasound assessment of the inferior vena cava distensibility index in mechanically ventilated children in the operating room

Abstract:
Background and aim
Point-of-care ultrasound imaging of the inferior vena cava distensibility index is a potential indicator for determining fluid overload and dehydration in the mechanically ventilated patients. Data on inferior vena cava distensibility index and inferior vena cava distensibility variability are limited in mechanically ventilated pediatric patients. That is why our aim in this study was to measure inferior vena cava distensibility index and to obtain mean values in pediatric patients, ventilated in the operating room before the ambulatory surgical procedure started.

Materials and methods
This crosssectional study was performed between February 2019 and February 2020. Ultrasonographic measurements were performed in a total of 125 children.

Results
In a period of 13 months, the measurements were performed in a total of 125 children, of which 120 (62.5% male) met the criteria and were included in the study. Overall inferior vena cava distensibility index (%): mean ± SD: 6.8 ± 4.0, median (min–max): 5.7 (1.4–19.6), IQR: 3.8–8.7. Overall inferior vena cava distensibility variability (%): mean ± SD: 6.5 ± 3.7, median (min–max): 5.5 (1.4–17.8), IQR: 3.7–8.4.

Conclusion
Our study is the largest series of children in the literature in which inferior vena cava distensibility index measurements were investigated.

Distensibility index
mechanically ventilation
children


Bottom-Up and Top-Down Approaches to Explore Sodium Dodecyl Sulfate and Soluplus on the Crystallization Inhibition and Dissolution of Felodipine Extrudates.

Abstract: The objectives of this study were to explore sodium dodecyl sulfate (SDS) and Soluplus on the crystallization inhibition and dissolution of felodipine (FLDP) extrudates by bottom-up and top-down approaches. FLDP extrudates with Soluplus and SDS were prepared by hot melt extrusion, and characterized by polarized light microscopy, differential scanning calorimetry, and fourier transform infrared spectroscopy. Results indicated that Soluplus inhibited FLDP crystallization, and the whole amorphous solid dispersions (ASDs) were binary FLDP-Soluplus (1:3) and ternary FLDP-Soluplus-SDS (1:2:0.15∼0.3 and 1:3:0.2∼0.4) extrudates. Internal SDS (5%-10%) decreased glass transition temperatures of FLDP-Soluplus-SDS ternary ASDs without presenting molecular interactions with FLDP or Soluplus. The enhanced dissolution rate of binary or ternary Soluplus-rich ASDs in the nonsink condition of 0.05% SDS was achieved. Bottom-up approach indicated that Soluplus was a much stronger crystal inhibitor to the supersaturated FLDP in solutions than SDS. Top-down approach demonstrated that SDS enhanced the dissolution of Soluplus-rich ASDs via wettability and complexation with Soluplus to accelerate the medium uptake and erosion kinetics of extrudates, but induced FLDP recrystallization and resulted in incomplete dissolution of FLDP-rich extrudates. In conclusion, top-down approach is a promising strategy to explore the mechanisms of ASDs' dissolution, and small amount of SDS enhances the dissolution rate of polymer-rich ASDs in the nonsink condition.

Chen|Jiali|J| Chen|Yuqi|Y| Huang|Wencong|W| Wang|Hanning|H| Du|Yang|Y| Xiong|Subin|S|

D017550:Spectroscopy, Fourier Transform Infrared

sodium dodecyl sulfate
soluplus
felodipine
hot melt extrusion
amorphous solid dispersions
medium uptake
erosion


PlantCrystals-Nanosized Plant Material for Improved Bioefficacy of Medical Plants.

Abstract:
PlantCrystals are obtained by milling plant material to sizes <10 µm. Due to the disruption of the plant cells, active compounds are easily released, rendering the PlantCrystal technology an effective and low-cost process for the production of environmentally friendly plant extracts. The extracts can be used to produce phytomedicines, nutritional supplements or cosmetic products. Previous studies could already demonstrate the use of PlantCrystals to improve the antimicrobial or antifungal activity of different plants. This study investigated whether PlantCrystal technology is suitable to produce plant derived formulations with high antioxidant capacity. The study also aimed to identify the most suitable production methods for this.

METHODS
Various plant materials and parts of plants, i.e., seeds, leaves and flowers, and different methods were employed for the production. PlantCrystals were characterized regarding size, physical stability and antioxidant capacity (AOC).

RESULTS
PlantCrystals with particles <1 µm were produced from the different plant materials. Both production methods, i.e., high-pressure homogenization, bead milling or the combination of both were suitable to obtain PlantCrystals. Nano milling of the plant material greatly affected their AOC and resulted in formulations with distinctly higher AOC when compared to classical extracts.

CONCLUSIONS
Rendering plant material into small sized particles is highly effective to obtain plant extracts with high biological efficacy.

Abraham|Abraham M|AM|
Alnemari|Reem M|RM|
Jacob|Claus|C|
Keck|Cornelia M|CM|

plants
bead milling
biological extracts
environmental toxicity
herbs
high pressure homogenization
nano-milling
nanocrystals
nanosuspension
nanotechnology


Predictors of Recurrence of AF in Patients After Radiofrequency Ablation.

Abstract: Catheter ablation is a well-known treatment for patients with AF. Despite the growing knowledge in the field, the identification of predictors of recurrence of AF after catheter ablation is one of the primary goals and is of major importance to improve long-term results of the procedure. The aim of this article is to provide an overview of what has been published in recent years and to summarise the major predictors, helping cardiac electrophysiologists in the selection of the right candidates for catheter ablation.

Garvanski|Iskren|I| Simova|Iana|I| Angelkov|Lazar|L| Matveev|Mikhail|M|

AF
catheter ablation
pulmonary vein isolation
recurrence of arrhythmia


Assessment of healthcare worker's hand hygiene and infection prevention practices of their personal belongings in a healthcare setting: a survey in pre COVID-19 era and literature review on standard disinfection practices.

Abstract:
Background
Healthcare workers' (HCW) hands and personnel belongings are vehicles of transmission of nosocomial infections. Knowledge, attitude, and practice of hand hygiene have been extensively studied suggesting adequate knowledge but poor compliance. Similar data on aprons, mobile phone and stethoscope disinfection practices are lacking. This becomes an extensively important topic of discussion in current COVID-19 pandemic where inadequacy in hygiene practices is devastating.

Aim
To study the knowledge, attitude, and infection prevention practices of HCWs aprons, electronic devices, stethoscopes, and hands.

Methods
A cross sectional questionnaire-based survey was conducted among HCWs of Medicine ward and ICU.

Results
Sixty-six HCWs responded to the survey. Awareness that hands, aprons, mobile phones, stethoscopes could cause cross transmission and knowledge of correct practices was present in majority of the respondents. Hand hygiene was performed by 65.2% of the respondents before touching a patient and 54.5% after touching the patient surroundings while 13.6% performed only when it was visibly soiled. Mobile phones and stethoscopes were disinfected by 13.6 and 30.3% of the respondents after each patient encounter, respectively. Aprons were washed after using them at a stretch for a median duration of 5 days (1-30 days). Forgetfulness, lack of reinforcement, lack of time, inadequate awareness on standard disinfection practices and fear of damaging electronic devices from disinfectants use were reasons for poor compliance.

Conclusions
There is an urgent need to spread awareness and formulate standard guidelines on disinfection practices especially for mobile phones, stethoscopes, and aprons in addition to reinforcing hand hygiene practices.

Kumar|Arvind|A|
Keri|Vishakh C|VC|
Khan|Maroof Ahmad|MA|
Ranjan|Piyush|P|
Rastogi|Neha|N|
Sahu|Monalisa|M|
Wig|Naveet|N|

Healthcare workers
Hands
COVID-19
Aprons
Mobile phones
Stethoscope
Hygiene practices


Brief Report: Physical Activity, Body Mass Index and Arterial Stiffness in Children with Autism Spectrum Disorder: Preliminary Findings.

Abstract: We examined the association between physical activity (PA), body mass index (BMI) and novel measures of subclinical cardiovascular disease (CVD) in 15 children with autism spectrum disorder (ASD) (mean age 7 ± 2 years, 2 girls). PA was objectively assessed using accelerometry as time spent in moderate-vigorous physical activity (MVPA). Arterial stiffness was measured via aortic pulse wave velocity (PWV) and taken as a marker of subclinical CVD risk. MVPA was inversely associated with aortic PWV (r = - 0.46, p < 0.05). BMI percentile was positively associated with aortic PWV (r = 0.61, p < 0.05). Overall findings suggest that reduced PA and higher body mass in children with ASD are associated with increased arterial stiffness which may have a detrimental impact on overall cardiovascular health.

Heffernan|Kevin S|KS|
Columna|Luis|L|
Russo|Natalie|N|
Myers|Beth A|BA|
Ashby|Christine E|CE|
Norris|Michael L|ML|
Barreira|Tiago V|TV|

Physical activity
Children
Autism spectrum disorder
Cardiovascular
Accelerometry
Blood pressure


Development of a school-based program for adolescents at-risk for depression in India: results from a pilot study.

Abstract: A majority of adolescents in India, who are at risk for depression, do not receive treatment or receive it when the psychopathology has become entrenched and chronic. The present pilot study was an endeavor to assess the felt needs of adolescents vis-à-vis the difficulties and stressors experienced by them. For this purpose, 300 students across three schools were screened using standardized measures. Another objective of the study was to develop and test a school-based Coping Skills Program to address adolescents at-risk for depression. Schools were sequentially assigned to intervention or control conditions; students of index (n=13) and control (n=6) groups were assessed at baseline, post-intervention, and 3 months follow-up. At post-intervention for the index group, all outcomes measures except coping skills-including depressive symptoms, negative cognitions, academic stress, and social problem-solving-showed change in the expected direction, this difference assuming significance at follow-up. The program was rated positively by students using anonymous feedback and there was low to nil perceived stigmatization. Results are discussed in the context of need for such intervention programs in India, and future scope of research involving larger samples.

Singhal|Meghna|M|
Manjula|M|M|
Vijay Sagar|K John|KJ|

D006301:Health Services Needs and Demand

Adolescents
Depression
Indicated program
School-based intervention


Prenatal prediction of neonatal haemodynamic adaptation after maternal hyperoxygenation.

Abstract:
The reactivity of the pulmonary vascular bed to the administration of oxygen is well established in the post-natal circulation. The vasoreactivity demonstrated by the fetal pulmonary artery Doppler waveform in response to maternal hyperoxia has been investigated. We sought to investigate the relationship between the reactivity of the fetal pulmonary arteries to hyperoxia and subsequent neonatal cardiac function in the early newborn period.

METHODS
This explorative study with convenience sampling measured pulsatility index (PI), resistance index (RI), acceleration time (AT), and ejection time (ET) from the fetal distal branch pulmonary artery (PA) at baseline and following maternal hyperoxygenation (MH). Oxygen was administered for 10 min at a rate of 12 L/min via a partial non-rebreather mask. A neonatal functional echocardiogram was performed within the first 24 h of life to assess ejection fraction (EF), left ventricular output (LVO), and neonatal pulmonary artery AT (nPAAT). This study was conducted in the Rotunda Hospital, Dublin, Ireland.

RESULTS
Forty-six women with a singleton pregnancy greater than or equal to 31 weeks' gestational age were prospectively recruited to the study. The median gestational age was 35 weeks. There was a decrease in fetal PAPI and PARI following MH and an increase in fetal PAAT, leading to an increase in PA AT:ET. Fetuses that responded to hyperoxygenation were more likely to have a higher LVO (135 ± 25 mL/kg/min vs 111 ± 21 mL/kg/min, p < 0.01) and EF (54 ± 9% vs 47 ± 7%,p = 0.03) in the early newborn period than those that did not respond to MH prenatally. These findings were not dependent on left ventricular size or mitral valve (MV) annular diameter but were related to an increased MV inflow. There was no difference in nPAAT.

CONCLUSION
These findings indicate a reduction in fetal pulmonary vascular resistance (PVR) and an increase in pulmonary blood flow and left atrial return following MH. The fetal response to hyperoxia reflected an optimal adaptation to postnatal life with rapid reduction in PVR increasing measured cardiac output.

Hyperoxygenation
Pulmonary artery Doppler
Doppler echocardiography


A Screening Method Using Anomaly Detection on a Smartphone for Patients With Carpal Tunnel Syndrome: Diagnostic Case-Control Study.

Abstract:
BACKGROUND
Carpal tunnel syndrome (CTS) is a medical condition caused by compression of the median nerve in the carpal tunnel due to aging or overuse of the hand. The symptoms include numbness of the fingers and atrophy of the thenar muscle. Thenar atrophy recovers slowly postoperatively; therefore, early diagnosis and surgery are important. While physical examinations and nerve conduction studies are used to diagnose CTS, problems with the diagnostic ability and equipment, respectively, exist. Despite research on a CTS-screening app that uses a tablet and machine learning, problems with the usage rate of tablets and data collection for machine learning remain.

OBJECTIVE
To make data collection for machine learning easier and more available, we developed a screening app for CTS using a smartphone and an anomaly detection algorithm, aiming to examine our system as a useful screening tool for CTS.

METHODS
In total, 36 participants were recruited, comprising 36 hands with CTS and 27 hands without CTS. Participants controlled the character in our app using their thumbs. We recorded the position of the thumbs and time; generated screening models that classified CTS and non-CTS using anomaly detection and an autoencoder; and calculated the sensitivity, specificity, and area under the curve (AUC).

RESULTS
Participants with and without CTS were classified with 94% sensitivity, 67% specificity, and an AUC of 0.86. When dividing the data by direction, the model with data in the same direction as the thumb opposition had the highest AUC of 0.99, 92% sensitivity, and 100% specificity.

CONCLUSIONS
Our app could reveal the difficulty of thumb opposition for patients with CTS and screen for CTS with high sensitivity and specificity. The app is highly accessible because of the use of smartphones and can be easily enhanced by anomaly detection.

screening
anomaly detection
smartphone
carpal tunnel syndrome
diagnostic
app
machine learning
data collection
algorithm
thumb


Positive mental health as a moderator of the association between risk factors and suicide ideation/behavior in psychiatric inpatients.

Abstract: In recent studies positive mental health has been shown as a resilience factor related to suicide ideation/behavior. It is not known if positive mental health buffers the effect of various risk factors (depression, perceived burdensomeness, hopelessness, childhood maltreatment) on suicide ideation/behavior in psychiatric inpatients-a high risk population. A total of 100 psychiatric inpatients were included in the survey. Four hierarchical regression analyses were conducted to examine, whether positive mental health moderates the association between the four risks factors and suicide ideation/behavior. Positive mental health was shown to moderate the association between perceived burdensomeness and suicide ideation/behavior. The association between the other three risk factors and suicide ideation/behavior was not moderated by positive mental health. Given the cross-sectional nature of the data, conclusions on causality cannot be drawn. The buffering effect of positive mental health suggests that positive mental health may improve the identification of individuals at risk of suicide ideation/behavior and may be an important area to target in the prevention and treatment of individuals at risk of suicide. Further research is needed.

Siegmann|Paula|P| Willutzki|Ulrike|U| Fritsch|Nathalie|N| Nyhuis|Peter|P| Wolter|Marcus|M| Teismann|Tobias|T|

Depression
Perceived burdensomeness
Hopelessness
Childhood maltreatment


Prevention of tau increase in cerebrospinal fluid of APP transgenic mice suggests downstream effect of BACE1 inhibition.

Abstract:
INTRODUCTION
The inhibition of the β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) is a main therapeutic approach for the treatment of Alzheimer's disease (AD). We previously reported an age-related increase of tau protein in the cerebrospinal fluid (CSF) of amyloid β (Aβ) precursor protein (APP) transgenic mice.

METHODS
APP transgenic mice were treated with a potent BACE1 inhibitor. CSF tau and CSF Aβ levels were assessed. A novel high-sensitivity tau sandwich immunoassay was developed.

RESULTS
We demonstrate that long-term BACE1 inhibition prevents CSF tau increase both in early-depositing APP transgenic mice and APP transgenic mice with moderate Aβ pathology.

DISCUSSION
Our results demonstrate that BACE1 inhibition not only reduces Aβ generation but also downstream AD pathophysiology. The tight correlation between Aβ aggregation in brain and CSF tau levels renders CSF tau a valuable marker to predict the effectiveness of BACE1 inhibitors in current clinical trials.

Schelle|Juliane|J|
Häsler|Lisa M|LM|
Göpfert|Jens C|JC|
Joos|Thomas O|TO|
Vanderstichele|Hugo|H|
Stoops|Erik|E|
Mandelkow|Eva-Maria|EM|
Neumann|Ulf|U|
Shimshek|Derya R|DR|
Staufenbiel|Matthias|M|
Jucker|Mathias|M|
Kaeser|Stephan A|SA|

D053829:Amyloid Precursor Protein Secretases

Tau
Treatment
Alzheimer's disease
CSF
BACE1 inhibitor
Biomarker


Spirulina platensis protects against microcystin-LR-induced toxicity in rats.

Abstract: Microcystis aeruginosa produces an abundant cyanotoxin (microcystins (MCs) in freshwater supplies. MCs have adverse health hazards to animals and humans. Microcystin-leucine-arginine (microcystin-LR or MC-LR) is the most studied among these MCs due to their high toxicity. So, this study was designed to evaluate the possible therapeutic role of the natural algal food supplement, Spirulina platensis (SP), against MC-LR-induced toxic effects in male Wistar rats. Forty rats were randomly divided into five groups. Control and SP groups orally administered distilled water and SP (1000 mg/kg/daily), respectively, for 21 days. MC-LR group was intraperitoneally injected with MC-LR (10 μg/kg/day) for 14 days. MC-LR-SP500 and MC-LR-SP1000 groups were orally treated with SP (500 and 1000 mg/kg, respectively) for 7 days and concomitantly with MC-LR for 14 days. MC-LR induced oxidative hepatorenal damage, cardiotoxicity, and neurotoxicity greatly, which was represented by reduction of reduced glutathione content and the activities of glutathione peroxidase, catalase, and superoxide dismutase and elevation of concentrations of nitric oxide and malondialdehyde in renal, hepatic, brain, and heart tissues. In addition, it increased serum levels of urea, creatinine, tumor necrosis factor-alfa, interleukin-1beta and interleukin-6 and serum activities of alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, creatine kinase, and creatine kinase-MB. However, S. platensis restored normal levels of measured serum parameters, ameliorated MC-LR-induced oxidative damage, and normalized tissue antioxidant biomarkers. In conclusion, SP alleviated MC-induced organ toxicities by mitigating oxidative and nitrosative stress and lipid peroxidation.

MC-LR
Brain
Heart
Antioxidant
Kidney
Liver
Microalgae
Oxidative stress
Reactive oxygen species


The lived experience of caregivers of persons with heart failure: A phenomenological study.

Abstract:
BACKGROUND
Heart failure (HF) patients need to follow a strict pharmacological and nonpharmacological regimen in order to counteract the burden of the disease, and informal caregivers are an important resource for HF patients in managing and coping with their disease. Few studies have examined the lived experience of these caregivers with a rigorous phenomenological approach, and none have been conducted in Italy.

AIM
To describe the lived experience of the caregivers of HF patients.

METHODS
A hermeneutic phenomenological method was used. Caregivers were enrolled in a HF clinic in central Italy. Interviews were analysed using a phenomenological approach. Credibility, dependability, confirmability and transferability were adopted in order to strengthen trustworthiness.

FINDINGS
Thirty HF caregivers (mean age: 53 years) were enrolled. Of these, 63% of the caregivers were female and 80% were patients' spouses or children. Six themes emerged: (1) fear and worry related to the illness; (2) life changes and restrictions; (3) burden due to caregiving; (4) uncertainty about illness management; (5) helping patients to cope with the illness; and (6) love and affection towards the patient.

CONCLUSION
The findings of our study may help providers to guide interventions for HF caregivers. Providers should be supportive of caregivers and provide them with education in order to reduce their fears and worries about the illness and to handle the course of HF and its symptoms. An empathetic and practical approach with caregivers that considers the patient-caregiver relationship may help caregivers to cope with the changes and restrictions that caregiving brings to their lives and to reduce their burden.

Petruzzo|Antonio|A|
Paturzo|Marco|M|
Naletto|Monica|M|
Cohen|Marlene Z|MZ|
Alvaro|Rosaria|R|
Vellone|Ercole|E|

lived experience
caregivers
Heart failure
phenomenology


The utility of hereditary thrombophilia testing among patients with unprovoked venous thromboembolism.

Abstract:
INTRODUCTION
Hereditary-thrombophilia (HT) testing is often sent during the evaluation of patients with unprovoked venous thromboembolism (VTE). This remains a frequent practice even though the results of such testing are often of unclear practical significance.

METHODS
We conducted a multicenter retrospective study to assess whether HT is associated with risk of recurrent VTE among patients who discontinue anticoagulation (AC) following an unprovoked VTE.

RESULTS
A total of 528 adult patients were included, 28% of whom (N = 110) tested positive for HT. Median follow-up was 55 months (IQR 40-66 months) following AC discontinuation. One hundred and twenty-four patients (23%) had a recurrent VTE during follow-up, including 29/110 with HT (26%) and 95/418 without HT (23%). Risk of recurrent VTE over time was similar between the two groups (logrank P = .47). The HR for recurrence among patients with HT was 1.17 (95% CI 0.76 to 1.81). On multivariable analysis, HT was not associated with recurrence of VTE (HR with HT = 1.07 (95% CI 0.69-1.65), P = .74). The only factor significantly associated with risk of VTE recurrence on multivariable analysis was presence of PE (as opposed to DVT alone) (HR = 1.54, 95% CI 1.02-2.30, P = .035).

CONCLUSION
The presence of HT was not associated with risk of recurrent VTE in this cohort of patients. These findings underscore the questionable clinical utility of routine thrombophilia testing among patient with unprovoked VTE and suggest that such testing should not be routinely pursued.

hereditary thrombophilia
thrombophilia testing
Venous thromboembolism (VTE)
recurrence


Body art education: the earlier, the better.

Abstract: Using the major format identified for successful prevention and intervention work, five "W" questions: what, why, whom, where, and who, plus one: how, this article first summarizes the current body art literature. Then, educational strategies specifically regarding the topic of tattoos and body piercing are presented for school nurses. These strategies can be used to create applicable, realistic information for young students before they are faced with decisions related to body art. The school nurse might be the first and only credible source of information the students receive related to body art in an education/health environment. Curriculum emphasis is on the decision making leading up to the action, and the major purposes, rather than on the markings or jewelry associated with procurement. Reducing decisional conflict while promoting positive development in the areas of empowerment, self-esteem, and maturing can help achieve stronger informed decision making.

Armstrong|Myrna L|ML|
Tustin|Jane|J|
Owen|Donna C|DC|
Koch|Jerome R|JR|
Roberts|Alden E|AE|

tattoos
body piercing
adolescence education
early education
elementary
middle school


In vitro and in vivo studies of novel fabricated bioactive dressings based on collagen and zinc oxide 3D scaffolds.

Abstract: The paper reports the synthesis and physico-chemical and biological characterization of novel wound dressings based on collagen and essential oil functionalized ZnO nanoparticles intended to improve the treatment of burns and to reduce the risk for developing wound sepsis in patients with burns or chronic wounds. The prepared wound dressings were physico-chemical characterized by Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). In vitro biocompatibility and cytotoxicity was proved on human fibroblast cells, antimicrobial potential was assessed on Gram positive and Gram negative bacteria models (Staphylococcus aureus and Escherichia coli, respectively), while in vivo studies were performed on a rat burn wound experimental model. Functionalized ZnO nanoparticles (NPs) proved to range 15-20 nm in size and contain about 1% orange essential oil (EO), which was utilized as a natural antimicrobial agent. NPs are grain-shapped and have a low tendency to form aggregates. No toxicity was noticed in vitro, as human fibroblasts maintained a normal growth and their membrane integrity in the presence of EO functionalized NPs. The capacity of the prepared wound dressings to act as implantable bioresorbable scaffolds that accelerates wounds healing along with an excellent biocompatibility, lack of cytotoxicity and a good antibacterial activity, make these materials promising and safe candidates for wound dressing, especially in burn patients.

Balaure|Paul Cătălin|PC|
Holban|Alina Maria|AM|
Grumezescu|Alexandru Mihai|AM|
Mogoşanu|George Dan|GD|
Bălşeanu|Tudor Adrian|TA|
Stan|Miruna S|MS|
Dinischiotu|Anca|A|
Volceanov|Adrian|A|
Mogoantă|Laurenţiu|L|

Collagen
ZnO nanoparticles
Antibacterial properties
Biodistribution
Burn wound healing
Nanocomposites


Inhibition of the platelet-derived growth factor receptor beta (PDGFRB) using gene silencing, crenolanib besylate, or imatinib mesylate hampers the malignant phenotype of mesothelioma cell lines.

Abstract: Malignant pleural mesothelioma (MPM) is a cancer of the pleural cavity resistant to chemotherapy. The identification of novel therapeutic targets is needed to improve its poor prognosis. Following a review of literature and a screening of specimens we found that platelet-derived growth factor receptor beta (PDGFRB) is over-expressed, but not somatically mutated, in MPM tissues. We aimed to ascertain whether PDGFRB is a MPM-cancer driver gene. The approaches employed included the use of gene silencing and the administration of small molecules, such as crenolanib and imatinib (PDGFR inhibitors) on MPM cell lines (IstMes2, Mero-14, Mero-25). Met5A cells were used as non-malignant mesothelial cell line. PDGFRB-silencing caused a decrease in the proliferation rate, and a reduced colony formation capacity, as well as an increase of the share of cells in sub-G1 and in G2 phase, and increased apoptotic rate of MPM cell lines. Loss of migration ability was also observed. Similar, or even further enhanced, results were obtained with crenolanib. Imatinib showed the least effective activity on the phenotype. In conclusion, our study highlights PDGFRB as target with a clear role in MPM tumorigenesis and provided a rationale to explore further the efficacy of crenolanib in MPM patients, with promising results.

Melaiu|Ombretta|O|
Catalano|Calogerina|C|
De Santi|Chiara|C|
Cipollini|Monica|M|
Figlioli|Gisella|G|
Pellè|Lucia|L|
Barone|Elisa|E|
Evangelista|Monica|M|
Guazzelli|Alice|A|
Boldrini|Laura|L|
Sensi|Elisa|E|
Bonotti|Alessandra|A|
Foddis|Rudy|R|
Cristaudo|Alfonso|A|
Mutti|Luciano|L|
Fontanini|Gabriella|G|
Gemignani|Federica|F|
Landi|Stefano|S|

PDGFRB
Malignant Pleural Mesothelioma
therapeutic targets
RNA interference
drug inhibitors


Molecular Landscape for Malignant Transformation in Diffuse Astrocytoma.

Abstract: Background  Malignant transformation (MT) of low-grade gliomas changes dramatically the natural history to poor prognosis. Currently, factors associated with MT of gliomas have been inconclusive, in particular, diffuse astrocytoma (DA). Objective  The present study aimed to explore the molecular abnormalities related to MT in the same patients with different MT stages. Methods  Twelve specimens from five DA patients with MT were genotyped using next-generation sequencing (NGS) to identify somatic variants in different stages of MT. We used cross-tabulated categorical biological variables and compared the mean of continuous variables to assess for association with MT. Results  Ten samples succussed to perform NGS from one male and four females, with ages ranging from 28 to 58 years. The extent of resection was commonly a partial resection following postoperative temozolomide with radiotherapy in 25% of cases. For molecular findings, poly-T-nucleotide insertion in isocitrate dehydrogenase 1 (IDH1) was significantly related to MT as a dose-response relationship (Mann-Whitney's U test, p  = 0.02). Also, mutations of KMT2C and GGT1 were frequently found in the present cohort, but those did not significantly differ between the two groups using Fisher's exact test. Conclusion  In summary, we identified a novel relationship between poly-T insertion polymorphisms that established the pathogenesis of MT in DA. A further study should be performed to confirm the molecular alteration with more patients.

malignant transformation
diffuse astrocytoma
whole genome sequencing


Characterization of novel microsatellite markers for Hyphantria cunea and implications for other Lepidoptera.

Abstract: This is the first report of microsatellite markers (simple sequence repeats, SSR) for fall webworm, Hyphantria cunea (Drury) (Lepidoptera: Arctiidae), an important quarantine pest in some European and Asian countries. Here, we developed 48 microsatellite markers for H. cunea from SSR enrichment libraries. Sequences isolated from libraries were sorted into four categories and analyzed. Our results suggest that sequences classified as Grouped should not be used for microsatellite primer design. The genetic diversity of microsatellite loci was assessed in 72 individuals from three populations. The number of alleles per locus ranged from 2 to 5 with an average of 3. The observed and expected heterozygosities of loci ranged from 0 to 0.958 and 0 to 0.773, respectively. A total of 18 out of 153 locus/population combinations deviated significantly from Hardy-Weinberg equilibrium. Moreover, significant linkage disequilibrium was detected in one pair of loci (1275 pairs in total). In the neutral test, two loci were grouped into the candidate category for positive selection and the remainder into the neutral category. In addition, a complex mutation pattern was observed for these loci, and F ST performed better than did R ST for the estimation of population differentiation in different mutation patterns. The results of the present study can be used for population genetic studies of H. cunea.

Cao|L J|LJ|
Wen|J B|JB|
Wei|S J|SJ|
Liu|J|J|
Yang|F|F|
Chen|M|M|

D000818:Animals
D015723:Gene Library
D006580:Genetic Carrier Screening
D014644:Genetic Variation
D005828:Genetics, Population
D015810:Linkage Disequilibrium
D018895:Microsatellite Repeats
D009036:Moths
D009154:Mutation
D013045:Species Specificity

microsatellite
Hyphantria cunea
Lepidoptera
mutation pattern
population differentiation


Feasibility and safety of Robot Suit HAL treatment for adolescents and adults with cerebral palsy.

Abstract: To investigate whether Robot Suit HAL treatment (HAL-T) is safe and feasible for gait disorders in adolescents and adults with cerebral palsy (CP). We tested HAL-T in adolescents and adults with bilateral spastic CP (four men, four women; mean age: 18.2 years). Three participants were classified as level III under the Gross Motor Function Classification System (GMFCS), and five were classified as level IV. The participants underwent HAL-T twice per week for 4 weeks. The outcome measures, which were assessed before and after HAL-T, included comfortable gait speed (CGS), step length (SL), cadence, and GMFCS level. Adverse events were noted. All participants completed the HAL-T sessions despite some mild adverse events occurring. The mean increases in CGS, SL, and cadence were 0.19 ± 0.14 m/s (p = 0.006), 0.09 ± 0.08 m (p = 0.020), and 18.0 ± 15.9 steps/min (p = 0.015), respectively. HAL-T is safe and feasible for gait disorders in patients with CP. HAL-T can significantly improve CGS, SL, and cadence and may be effective for improving walking ability in adolescents and adults with CP.

Ueno|Tomoyuki|T| Watanabe|Hiroki|H| Kawamoto|Hiroaki|H| Shimizu|Yukiyo|Y| Endo|Ayumu|A| Shimizu|Tomoe|T| Ishikawa|Kimihisa|K| Kadone|Hideki|H| Ohto|Tatsuyuki|T| Kamada|Hiroshi|H| Marushima|Aiki|A| Hada|Yasushi|Y| Muroi|Ai|A| Sankai|Yoshiyuki|Y| Ishikawa|Eiichi|E| Matsumura|Akira|A| Yamazaki|Masashi|M|

Cerebral palsy
Gait disorders
Robot-assisted gait therapy


Seroprevalence and risk factors for selected respiratory and reproductive tract pathogen exposure in European bison (Bison bonasus) in Poland.

Abstract: After the complete extinction from the wild of European bison (Bison bonasus) at the beginning of the twentieth century, the worldwide species population was restored to approximately 5500 individuals, with the species however remaining endangered. Despite numerous studies on the ecology and genetics of European bison, the threats of infectious diseases have been largely unexamined. The aim of this study was to screen the exposure of the world's largest population of European bison to the pathogens, which may influence the condition and development of the endangered species. A total of 240 free-ranging and captive European bison from eight main Polish populations sampled were tested for the presence of specific antibodies against ten different viruses, bacteria or protozoan. The samples were collected from chemically immobilized, selectively culled or found dead animals. Based on serology, the exposure to bovine viral diarrhea virus (BVDV), bovine herpesvirus type 1 (BoHV-1), Mycoplasma and Brucella spp. was determined as rather accidental. Using gamma-interferon assay followed by Mycobacterium tuberculosis subs. caprae detection in tissues, diagnosis of bovine tuberculosis was made for 6 out of 78 (7.7%) bison from one captive herd. The highest seroprevalence was found for bovine adenovirus type 3 (BAdV-3) -60.2% and bovine parainfluenza type 3 (PIV-3) -34.0%, while the antibodies against bovine respiratory syncytial virus (BRSV), Toxoplasma gondii and Leptospira spp. were found in 10.4%, 10.4% and 8.7% of samples, respectively. In the multivariable statistical analysis using generalized linear mixed models (GLMMS), the risk factors for PIV-3 seropositivity included population type (free-living/captive), age and health status (apparently healthy/eliminated due to the poor condition). Higher risk of BAdV-3 seropositive result was observed in free-living female European bison. The high BAdV-3 and PIV-3 seroprevalences may suggest involvement of these pathogens in the most frequently observed respiratory disorders in European bison. Moreover, this is the first study demonstrating BAdV-3 exposure in the species.

Krzysiak|Michał K|MK|
Jabłoński|Artur|A|
Iwaniak|Wojciech|W|
Krajewska|Monika|M|
Kęsik-Maliszewska|Julia|J|
Larska|Magdalena|M|

D000818:Animals
D001424:Bacterial Infections
D016164:Bison
D011044:Poland
D011529:Protozoan Infections, Animal
D060737:Reproductive Tract Infections
D012141:Respiratory Tract Infections
D012307:Risk Factors
D016036:Seroepidemiologic Studies
D014777:Virus Diseases

European bison
BVDV
BoHV-1
Brucella spp.
BAdV-3
PIV-3
BRSV
Toxoplasma gondii
Leptospira spp.
Mycobacterium spp.
Mycoplasma spp.


The Effect of Horse Shoeing with Egg Bar Shoes and Shoes with Wedge Pads on the Results of Thermal Imaging of the Equine Distal Limb.

Abstract: The presented manuscript provides reference for practitioners when measuring normal hoof temperature, as well as controlling the temperature after shoeing with particular shoes. The aim of this study was to determine the effect of horse shoeing with egg bar shoes and shoes with wedge pads on hoof temperature measured by thermography. This was a prospective study conducted on 16 horses. The horses were divided into two groups: horses from group 1 were shod with egg bar shoes, while horses from group 2 were shod with shoes with wedge pads. Thermographic examination was performed below the metacarpophalangeal joint before and one month after shoeing. After shoeing with egg bar shoes, there was a decrease in the median of the minimal temperature in the palmar view. After shoeing with wedge pads, thermography revealed decreased hoof temperature in the dorsal and palmar views. Horse shoes may have a negative impact on the blood circulation and metabolism within the distal part of the limb; however, our study found this only to a minor extent.

equine
digital blood flow
infrared thermography


Genetic diversity and symbiotic effectiveness of Bradyrhizobium strains nodulating selected annual grain legumes growing in Ethiopia.

Abstract: Vigna unguiculata, Vigna radiata and Arachis hypogaea growing in Ethiopia are nodulated by a genetically diverse group of Bradyrhizobium strains. To determine the genetic identity and symbiotic effectiveness of these bacteria, a collection of 36 test strains originating from the root nodules of the three hosts was investigated using multilocus sequence analyses (MLSA) of core genes including 16S rRNA, recA, glnII, gyrB, atpD and dnaK. Sequence analysis of nodA and nifH genes along with tests for symbiotic effectiveness using δ15N analysis were also carried out. The phylogenetic trees derived from the MLSA grouped most test strains into four well-supported distinct positions designated as genospecies I-IV. The maximum likelihood (ML) tree that was constructed based on the nodA gene sequences separated the entire test strains into two lineages, where the majority of the test strains were clustered on one of a well-supported large branch that comprise Bradyrhizobium species from the tropics. This clearly suggested the monophyletic origin of the nodA genes within the bradyrhizobia of tropical origin. The δ15N-based symbiotic effectiveness test of seven selected strains revealed that strains GN100 (δ15N=0.73) and GN102 (δ15N=0.79) were highly effective nitrogen fixers when inoculated to cowpea, thus can be considered as inoculants in cowpea production. It was concluded that Ethiopian soils are a hotspot for rhizobial diversity. This calls for further research to unravel as yet unknown bradyrhizobia nodulating legume host species growing in the country. In this respect, prospective research should also address the mechanisms of symbiotic specificity that could lead to high nitrogen fixation in target legumes.

symbiotic effectiveness
Bradyrhizobium
Ethiopia
MLSA
Genospecies


Long Term Exposure to Low Ethylene and Storage Temperatures Delays Calyx Senescence and Maintains 'Afourer' Mandarins and Navel Oranges Quality.

Abstract: Calyx browning and internal quality loss are major physiological causes for the loss of quality in citrus fruit during storage. While the symptoms of calyx senescence are only superficial, it can affect the appearance and consumer acceptability of citrus fruit. In this study, continuous ethylene exposure at different storage temperatures was investigated to assess their effect on calyx senescence and internal qualities in 'Afourer' mandarin and Navel orange fruit during storage. 'Afourer' mandarin fruit were stored at ≤0.001 (equivalent to ethylene-free air), 0.01, 0.1 and 1 µL L-1 of ethylene at either 5, 10 or 20 °C, whilst in a parallel experiment, Navel oranges were exposed to ≤0.001, 0.1 and 1 µL L-1 ethylene at either 1 or 10 °C. Changes in external and internal postharvest quality parameters were assessed for up to 8 weeks for 'Afourer' mandarins and 10 weeks for Navel oranges. At all storage temperatures, high levels of ethylene were found to increase the level of calyx senescence, weight loss, loss of fruit firmness and respiration rates. Also, there were significant effects of ethylene and storage temperatures on total soluble solids (TSS) content, titratable acidity (TA), and ethanol accumulation in both citrus species. Continuous exposure to high ethylene also significantly reduced vitamin C and ferric reducing antioxidant power (FRAP) in 'Afourer' mandarins after 8 weeks of storage. Overall, ethylene treatments had a significant effect on both the external and internal qualities of the fruit during storage. The relationship between ethylene concentrations and storage temperatures demonstrate that lowering atmospheric ethylene levels at reduced storage temperatures maintain fruit quality during long term storage.

Alhassan|Nasiru|N|
Golding|John B|JB|0000-0002-6309-2745
Wills|Ron B H|RBH|
Bowyer|Michael C|MC|
Pristijono|Penta|P|

ethylene
temperature
calyx senescence
mandarins
oranges
citrus


Genomic integration of Wnt/β-catenin and BMP/Smad1 signaling coordinates foregut and hindgut transcriptional programs.

Abstract: Digestive system development is orchestrated by combinatorial signaling interactions between endoderm and mesoderm, but how these signals are interpreted in the genome is poorly understood. Here we identified the transcriptomes of Xenopus foregut and hindgut progenitors, which are conserved with mammals. Using RNA-seq and ChIP-seq we show that BMP/Smad1 regulates dorsal-ventral gene expression in both the endoderm and mesoderm, whereas Wnt/β-catenin acts as a genome-wide toggle between foregut and hindgut programs. Unexpectedly, β-catenin and Smad1 binding were associated with both transcriptional activation and repression, with Wnt-repressed genes often lacking canonical Tcf DNA binding motifs, suggesting a novel mode of direct repression. Combinatorial Wnt and BMP signaling was mediated by Smad1 and β-catenin co-occupying hundreds of cis-regulatory DNA elements, and by a crosstalk whereby Wnt negatively regulates BMP ligand expression in the foregut. These results extend our understanding of gastrointestinal organogenesis and of how Wnt and BMP might coordinate genomic responses in other contexts.

Stevens|Mariana L|ML|
Chaturvedi|Praneet|P|
Rankin|Scott A|SA|
Macdonald|Melissa|M|
Jagannathan|Sajjeev|S|
Yukawa|Masashi|M|
Barski|Artem|A|
Zorn|Aaron M|AM|0000-0003-3217-3590

D018507:Gene Expression Regulation, Developmental

Wnt β-Catenin BMP Smad1 Foregut Hindgut Endoderm Mesoderm Xenopus RNA-seq ChIP-seq


Understanding Crystal Cleavability and Physical Properties of Crystal Surfaces Using in Silico Simulation.

Abstract: In the drug formulation process, compound dissolution rate and wettability may be improved by grinding. However, there is no method to understand the effects of the wettability of the crystal facets of the ground product. Here, acetylsalicylic acid (ASA) was used to evaluate the changes in crystal morphology and dissolution rate by jet milling using powder X-ray diffraction and in silico simulation. Several cleavage facets were observed in cube crystals, and the (0 0 2) facet was observed in plate crystals. Furthermore, the dissolution rate of the ground samples per unit area decreased with the cleavage of the (1 0 0) and (0 0 2) facets. The polar surface energy of the ground sample decreased with increasing grinding pressure. The simulation results showed that the absolute attachment energy of the (1 0 0) and (0 0 2) facets was lower than that of the other crystal facets. Moreover, atoms with low polarity were present on the crystal surface of (0 0 2). The wettability and dissolution rate of the (0 0 2) facet were worse than those of the (1 0 0) facet. It was suggested that the dissolution rate of the ground sample was affected by the wettability of the crystal facet caused by the cleavage. The cleavability and wettability may be understood by simulation.

Hatanaka|Toshiaki|T| Yoshihashi|Yasuo|Y| Terada|Katsuhide|K| Yonemochi|Etsuo|E|

in silico simulation
wettability
crystal facet
acetylsalicylic acid
cleavage


Social Determinants of Depression: Social Cohesion, Negative Life Events, and Depression Among People Living with HIV/Aids in Nigeria, West Africa.

Abstract:
BACKGROUND
People Living with HIV/AIDS (PLWHA) continue to face persistent and deep rooted social barriers. Incidentally, studies in social determinants of depression are very limited, necessitating this study, which examined social determinants of depression and the impact of these determinants on depression.

METHODS
This was a hospital based, cross sectional descriptive study of three hundred adult HIV/AIDS patients, attending the HIV clinic of Kwara State Specialist Hospital, Sobi, Ilorin, Nigeria. Depressive symptoms were measured by the PHQ-9 rating scale. Three variables of social determinants of depression: socio-economic status (years of school and self-reported economic status of family), social cohesion, and negative life events were examined.

RESULTS
The self-reported economic status of the family varied from good 35(11.7%), average 162(54%), and poor among 103(34.3%) of the respondents. Social cohesion was low in 199(66.3%), fair in 65(21.7%) and high among 36(12%) of the respondents. There was significant association between social cohesion, negative life events, and depression.

CONCLUSION AND GLOBAL HEALTH IMPLICATIONS
Income was the most significant socio-economic determinant. Majority had very low social cohesion and more negative life events, while those with below average years of schooling were more depressed. These are statistically significant. Social determinants of depression should be given a lot of emphasis, when addressing the issue of depression, if we are to meaningfully tackle this increasing scourge in our society.

Shittu|Rasaki O|RO|
Issa|Baba A|BA|
Olanrewaju|Ganiyu T|GT|
Mahmoud|Abdulraheem O|AO|
Odeigah|Louis O|LO|
Sule|Abdullateef G|AG|

Social determinants
Depression
Social cohesion
Negative life events
People living with HIV/AIDS
Nigeria
PLWHA


Water wavenumber calibration for visible light optical coherence tomography.

Abstract:
SIGNIFICANCE
Visible light optical coherence tomography (OCT) is emerging for spectroscopic and ultrahigh resolution imaging, but challenges remain. Depth-dependent dispersion limits retinal image quality and current correction approaches are cumbersome. Inconsistent group refractive indices during image reconstruction also limit reproducibility.

AIM
To introduce and evaluate water wavenumber calibration (WWC), which corrects depth-dependent dispersion and provides an accurate depth axis in water.

APPROACH
Enabled by a visible light OCT spectrometer configuration with a 3- to 4-dB sensitivity roll-off over 1 mm in air across a 90-nm bandwidth, we determine the spectral phase of a 1-mm water cell, an affine function of water wavenumber. Via WWC, we reconstruct visible light OCT human retinal images with 1.3-μm depth resolution in water.

RESULTS
Images clearly reveal Bruch's membrane, inner plexiform layer lamination, and a thin nerve fiber layer in the temporal parafovea. WWC halves the processing time, while achieving the same image definition as an assumption-free gold standard approach, suggesting that water wavenumber is a suitable proxy for tissue wavenumber. WWC also provides a depth axis in water without explicitly assuming a group refractive index.

CONCLUSIONS
WWC is a simple method that helps to realize the full potential of visible light OCT.

Zhang|Tingwei|T|
Kho|Aaron M|AM|
Srinivasan|Vivek J|VJ|

wavenumber calibration
optical coherence tomography
retinal imaging
dispersion compensation


Rhein Derivatives, A Promising Pivot?

Abstract: Rhein, an anthraquinone derivative, has been employed widely, especially for the treatment of intractable diseases like diabetic nephropathy, arthritis, and cancer in a unique action mechanism. In the last decades, considerable efforts have been made in structural modification of rhein. This paper reviewed patents on pharmacological activity and therapeutic application of rhein and its derivatives from 1978 to 2018. Particularly, an analysis of patents was made, with the top 10 most valuable patents presented, and the interpretation of the legal status of patents was given. Given the properties of superior pharmacological activity, rich resources, cheap price, low toxicity, and mature extraction process, it is believed that an in-depth investigation on rhein and its derivatives is worth trying.

Pei|Rui|R| Jiang|Yueping|Y| Lei|Guanghua|G| Chen|Jingjing|J| Liu|Manhua|M| Liu|Shao|S|

rhein
anthraquinone derivative
patent
pharmacological activity
therapeutic application
drug development


Artesunate induces ROS-dependent apoptosis via a Bax-mediated intrinsic pathway in Huh-7 and Hep3B cells.

Abstract: Artesunate (ARS), an artemisinin derivative, has been demonstrated to possess antitumor activity in various human tumor cells. This study aims to investigate the molecular mechanism by which ARS induces apoptosis in human hepatocellular carcinoma cells (Huh-7 and Hep3B cells). ARS effectively induced externalization of phosphatidylserine (PS), depolarization of mitochondrial membrane, release of cytochrome c from mitochondria, and activation of caspase-9 and 3, characteristics of the intrinsic apoptosis. Pretreatment with antioxidant N-Acetyle-Cysteine (NAC) completely blocked ARS-induced reactive oxygen species (ROS) generation and apoptosis in the two cell lines. ARS increased cellular iron ions level in Huh-7/Hep3B cells, but decreased cellular iron ions level in HepG2 cells. Pifithrin-alpha (PFT), an inhibitor of p53, significantly enhanced ARS-induced cytotoxicity in HepG2 cells, and the forced expression of wild-type p53 significantly enhanced ARS-induced cytotoxicity in Hep3B cells. In addition, ARS induced translocation and activation of the proapoptotic Bax, and silencing Bax remarkably inhibited ARS-induced apoptosis and ΔΨm collapse in Huh-7 and Hep3B cells, demonstrating the key role of Bax in ARS-induced apoptosis. Collectively, our data demonstrate that ARS induces ROS-dependent apoptosis via a Bax-mediated intrinsic pathway in Huh-7 and Hep3B cells.

Pang|Yilin|Y| Qin|Guiqi|G| Wu|Liping|L| Wang|Xiaoping|X| Chen|Tongsheng|T|

D050998:bcl-2 Homologous Antagonist-Killer Protein

Artesunate
Apoptosis
Hepatocellular carcinoma cells
ROS
Bax
Caspases


Synthesis and biological evaluation of 2-amino-5-aryl-3-benzylthiopyridine scaffold based potent c-Met inhibitors.

Abstract: A series of 2-amino-N-benzylpyridine-3-carboxnamides, 2-amino-N-benzylpyridine-3-sulfonamides and 2-amino-3-benzylthiopyridines against c-Met were designed by means of bioisosteric replacement and docking analysis. Optimization of the 2-amino-3-benzylthiopyridine scaffold led to the identification of compound (R)-10b displaying c-Met inhibition with an IC50 up to 7.7nM. In the cytotoxic evaluation, compound (R)-10b effectively inhibited the proliferation of c-Met addictive human cancer cell lines (IC50 from 0.19 to 0.71μM) and c-Met activation-mediated cell metastasis. At a dose of 100mg/Kg, (R)-10b evidently inhibited tumor growth (45%) in NIH-3T3/TPR-Met xenograft model. Of note, (R)-10b could overcome c-Met-activation mediated gefitinib-resistance, which indicated its potential use for drug combination. Taken together, 2-amino-3-benzylthiopyridine scaffold was first disclosed and exhibited promising pharmacological profiles against c-Met, which left room for further exploration.

Zhang|Dengyou|D| Zhang|Xiaowei|X| Ai|Jing|J| Zhai|Yun|Y| Liang|Zhongjie|Z| Wang|Ying|Y| Chen|Yi|Y| Li|Chunpu|C| Zhao|Fei|F| Jiang|Hualiang|H| Geng|Meiyu|M| Luo|Cheng|C| Liu|Hong|H|

2-Amino-5-aryl-3-benzylthiopyridine
c-Met
Receptor tyrosine kinase


Dimensionality and differential item endorsement of depressive symptoms among aging Black populations in South Africa: Findings from the HAALSI study.

Abstract:
BACKGROUND
The Center for Epidemiologic Studies-Depression (CES-D) scale is a widely used measure of depressive symptoms, but its construct validity has not been adequately assessed in sub-Saharan Africa. This study validates the CES-D among an aging Shangaan-speaking and predominantly Black African sample in rural South Africa, with a special emphasis on gender differences.

METHODS
An 8-item CES-D scale was administered in Shangaan to 5059 respondents, aged 40+ years, residing in Agincourt, South Africa. We used Cronbach's alpha and exploratory and confirmatory factor analysis to examine and confirm dimensionality of the CES-D scale. Differential endorsement of CES-D items by gender were assessed using the Mantel-Haenszel (MH) odds ratio test.

RESULTS
Reliability of the CES-D scale differed by gender with women reporting higher internal consistency on items than men. A two-factor solution was retained and confirmed representing two latent factors: (1) Negative Affect (six items) and (2) Diminished Positive Affect (two items). MH results showed that men exhibited significantly higher odds of putting an effort in everything that they did (OR: 1.33, 95% CI: 1.15-1.54) and lower odds of feeling depressed (OR: 0.71, 95% CI: 0.56-0.89) and having restless sleep (OR: 0.67, 95% CI:0.58-0.77) than women.

LIMITATIONS
Analyses were limited to a dichotomous, short form of the CES-D, a self-reported population-based measure.

CONCLUSION
Aging Black Africans differ in endorsing affective and somatic items on the CES-D scale by gender, which may lead to skewed population-level estimates of depression in key subpopulations. These findings highlight the importance of continued research disentangling cross-cultural and gendered nuances of depression measurements.

Adams|Leslie B|LB|
Farrell|Meagan|M|
Mall|Sumaya|S|
Mahlalela|Nomsa|N|
Berkman|Lisa|L|

D011569:Psychiatric Status Rating Scales

Depression
South Africa
CES-D
Gender
Factor analysis
Race


Antiadenoviral effects of ganciclovir in types inducing keratoconjunctivitis by quantitative polymerase chain reaction methods.

Abstract:
PURPOSE
The most common external ocular viral infections are caused by several human adenovirus (HAdV) types. Ganciclovir has been reported to inhibit cytomegalovirus, herpes simplex virus types 1 and 2, varicella zoster virus, and Epstein-Barr virus. Ganciclovir ophthalmic gel, 0.15% (Virgan®) is commercially available for cytomegalovirus or herpes virus keratitis. However its inhibitory activity against HAdV is reported only for types 2 and 5. We investigated the antiadenoviral activity of ganciclovir in vitro in several common types currently inducing keratoconjunctivitis.

MATERIALS AND METHODS
A549 cells were used for viral cell culture, and adenovirus types 3 (HAdV3; species B), 4 (species E), and 8, 19a, and 37 (species D) were used. After pretreatment of A549 with serial dilutions of ganciclovir for 24 hours, adenovirus was cultured for 7 days, and adenoviral deoxyribonucleic acid was quantitatively measured by real-time polymerase chain reaction (PCR).

RESULTS
The 50% cytotoxic concentration of ganciclovir was 212 μg/mL. The 50% effective concentration of ganciclovir obtained by real-time PCR ranged between 2.64 and 5.10 μg/mL. A significant inhibitory effect of ganciclovir on adenoviral proliferation was found in all types in a dose-dependent manner. The selectivity index of ganciclovir ranged between 41.6 and 80.3.

CONCLUSION
Ganciclovir showed significant inhibitory activity against HAdV3, 4, 8, 19a, and 37, which induce epidemic keratoconjunctivitis. These results indicate that ganciclovir is a possible candidate for the treatment of HAdV keratoconjunctivitis, and ganciclovir ophthalmic gel could be applied to adenoviral keratoconjunctivitis in the future.

ganciclovir
adenovirus
epidemic keratoconjunctivitis
A549 cell line
nucleoside analog


Cataloguing the taxonomic origins of sequences from a heterogeneous sample using phylogenomics: applications in adventitious agent detection.

Abstract:
UNLABELLED
We have designed and implemented a software system, named PhyloID™, that can be used to detect putative adventitious agents in biological samples characterized by next-generation sequencing. PhyloID is run in two steps, each being a self-contained automated process amenable to GMP validation. The first module, MiLY, is responsible for assembling individual sequence reads into contigs, and annotating all sequences with a unique sequence identifier, the number of reads in each contig, and the length of the sequence. The trimmed, assembled and annotated data are then processed by PhyloID's second module, NGmapper. NGmapper takes the FASTA-formatted output from MiLY and identifies the taxonomic origins of the contigs and singletons therein. It compares each sequence's BLASTN hit profile against the patterns of evolutionary relationships described within phylogenomic distance matrices for all of the various taxonomic groups, in order to find the best fit. NGmapper then produces lists of taxonomic assignments in both summarized and detailed form, and tree files for viewing results graphically. We optimized PhyloID's parameters and measured its performance using simulated metagenomic data and subsets of the reference phylogenies. PhyloID's precision and recall in identifying simulated sequences were measured by information retrieval analysis, focusing on read length, read number, sequence accuracy, background complexity, taxonomy and reference data coverage. We found PhyloID to be highly accurate and quantitative in its taxonomic mapping of sequences, with excellent precision, sensitivity and robustness. The degree of taxonomic representation available in publicly available databases remains an issue, as expected, for any sequence classifier, but community sequencing efforts are poised to overcome this problem. In order to illustrate real-world usage of the application, we also describe some simple spike-recovery experiments as well as a multi-site comparative characterization of a viral suspension. These data help to illustrate, to corroborate, and to extend results using simulated data.

LAY ABSTRACT
In order to address gaps in the detection of contaminating viruses and microorganisms in vaccines and other biologicals, manufacturers are exploring the use of new technologies that promise greater sensitivity and breadth of coverage. One challenge in implementing such new methods is the complexity of analysis of the "big data" generated by these new instruments: hundreds of millions of sequence reads (segments of genetic material from viruses and cells) need to be compared against a vast and growing number of entries in genetic databases, in order to come up with a confident identification. These large-scale analyses must furthermore be carried out within the strict regulatory environment that governs the industry. We have developed an automated software pipeline named PhyloID™ that is capable of identifying viruses and microorganisms from large-scale sequence data. Using simulated data as well as real samples, we show that PhyloID is both sensitive and accurate in identifying any type of potential contaminant. Such a powerful new assay will be an important addition to the adventitious agent testing package, providing further assurance about product safety.

Charlebois|Robert L|RL|
Ng|Siemon H S|SH|
Gisonni-Lex|Lucy|L|
Mallet|Laurent|L|

Adventitious agent detection
Metagenomics
Bioinformatics


Evaluating vaspin and adiponectin in postmenopausal women with endometrial cancer.

Abstract: Insulin resistance is a well-documented risk factor for the development of endometrial cancer. Adiponectin and vaspin are insulin-sensitizing proteins that are secreted from adipose tissue. A clear association between serum levels of adipokines and endometrial cancer has yet to be established. The study group consisted of postmenopausal women with confirmed endometrial cancer, whereas patients with benign endometrial conditions constituted the control group. The two groups were compared in terms of insulin resistance and serum levels of adiponectin and vaspin. A total of 60 patients with confirmed endometrial cancer and 70 controls with benign endometrial conditions (polyps and atrophy) were enrolled. Median homeostasis model assessment of insulin resistance value was significantly higher in the study group compared with the control group (2.93 vs 1.27, P<0.0001), whereas mean quantitative insulin sensitivity check index value was significantly lower (0.33 ± 0.02 vs 0.37 ± 0.37, P<0.0001). Median values for both adiponectin and vaspin were significantly lower in patients with endometrial cancer compared with the control group (4.09 vs 17.13 μg/ml, P<0.0001 and 0.21 vs 0.39 ng/ml, P<0.0001 respectively). Low levels of both adiponectin and vaspin were found to be significantly associated with an increased risk for endometrial cancer. Following adjustment for confounding factors, the respective odds ratios for endometrial cancer in patients in the first tertile compared with those in the third tertile were 10.80 (2.76-42.24; P=0.001) and 13.23 (2.94-59.64; P=0.001). Our results show that lower levels of circulating adiponectin and vaspin levels are associated with an increased risk of developing endometrial cancer.

Erdogan|Serpil|S|
Sezer|Sevilay|S|
Baser|Eralp|E|
Gun-Eryilmaz|Ozlem|O|
Gungor|Tayfun|T|
Uysal|Sema|S|
Yilmaz|Fatma Meric|FM|

vaspin
adiponectin
endometrial cancer
insulin resistance


How Does the Phenol Structure Influence the Results of the Folin-Ciocalteu Assay?

Abstract: Plants produce a diverse array of secondary metabolites that are generally nonessential but facilitate ecological interactions. Fruits, vegetables, seeds and nuts can accumulate bioactive secondary metabolites with health-promoting properties, including the potent antioxidant activities of phenolic compounds. Several in vitro assays have been developed to measure the polyphenol content and antioxidant activity of plant extracts, e.g., the simple and highly popular Folin-Ciocalteu (FC) assay. However, the literature contains a number of different descriptions of the assay and it is unclear whether the assay measures the polyphenol content or reducing capacity of the sample. To determine the influence of phenolic structures on the outcome of the FC assay, we tested phenols representing different subgroups (phenolic acids, flavonols, flavanols, dihydrochalcones and flavanones). We observed different results for each reference substance and subgroup. Accordingly, we concluded that the FC assay does not measure the polyphenol content of a sample but determines its reducing capacity instead. Assigning the substances to five structural classes showed that the FC results depend on the number of fulfilled Bors criteria. If a molecule fulfills none of the Bors criteria, the FC results depend on the number of OH groups. We did not find a correlation with other single electron transfer assays (e.g., ABTS and DPPH assays). Furthermore, the FC assay was compatible with all five subgroups and should be preferred over the DPPH assay, which is specific for extracts rich in dihydrochalcones or flavanones.

reducing capacity
phenolic acids
antioxidant effect
flavonoids
structure-activity relationship


"Atypical" salivary gland fine needle aspiration: Risk of malignancy and interinstitutional variability.

Abstract:
BACKGROUND
Fine needle aspiration (FNA) is widely used in the diagnosis of salivary gland lesions. Salivary gland FNAs are often difficult to diagnose because of morphologic heterogeneity, a small but significant number of the FNAs yield "atypical" diagnosis. However, systematic evaluation of the risk of malignancy (ROM) of the atypical diagnoses across institutions and the variability of ROM among institutions are still lacking.

METHODS
Salivary gland FNAs from five tertiary medical centers of United States, Europe and China were reviewed. Cases with "atypical" diagnosis and histological follow-up were included in this study. The diagnostic category of "atypical" was adopted from Milan System for Reporting Salivary Gland Cytopathology (MSRSGC, personal communication).

RESULTS
Among the 12,606 salivary gland FNAs, 504 (4.0%) cases were reported as "atypical", with 154 cases (30.6%) having histological follow-ups. Histological follow-ups revealed 94 malignant tumors (61.0%, 57 lymphomas, 33 carcinomas, 2 sarcomas, 1 metastatic melanoma, 1 metastatic neuroblastoma), 33 benign tumors (21.4%), and 25 benign lesions (16.2%). ROM in the subset of "atypical" cases with histological follow-up from different institutions vary from 73.08% to 0.00%, the Pearson chi2  = 24.38 and P < .001.

CONCLUSIONS
More than half of the subset of "atypical" salivary gland FNAs with histological resection turned out to be malignant tumors; another one-fourth were benign neoplasms. Further, the highly variable ROMs of the "atypical" category amongst different institutions likely reflect the variable practices at each individual institution.

atypical
risk of malignancy
interinstitutional variability
salivary gland FNA


Development of generic raman models for a GS-KOTM CHO platform process.

Abstract: The monitoring and control of bioprocesses is of the utmost importance in order to provide a consistent, safe, and high-quality product for consumers. Current monitoring and control schemes rely on infrequent and time consuming offline sampling methods, which inherently leads to some variability in the process which may impact the product quality profile. As part of Lonza's dedication to process analytical technology (PAT) initiatives this study evaluated the ability to generate generic calibration models, which are independent of the cell line, using Raman probes to monitor changes in glucose, lactate, glutamate, ammonium, viable cell concentration (VCC), total cell concentration (TCC) and product concentration. Calibration models were developed from cell culture using two different CHOK1SV GS-KOTM cell lines producing different monoclonal antibodies (mAbs). Developed predictive models, measured changes in glucose, lactate, ammonium, VCC, and TCC with average prediction errors of 0.44, 0.23, 0.03 g L-1 , 1.90 × 106 cells mL-1 , and 1.85 × 106 cells mL-1 , respectively over the course of cell culture with minimal cell line dependence. The development of these generic models allows the application of spectroscopic PAT techniques in clinical and commercial manufacturing environments, where processes are typically run once or twice in GMP manufacturing based on a common platform process. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:730-737, 2018.

process analytical technology
predictive modelling
inline Raman spectroscopy


Effect of Monochromatic Infrared Energy on Quality of Life and Intraepidermal Nerve Fiber Density in Painful Diabetic Neuropathy: A Randomized, Sham Control Study.

Abstract:
Background
Monochromatic infrared energy (MIRE) has evoked mixed results for symptomatic relief of painful diabetic peripheral neuropathy (DPN). However, intraepidermal nerve-fiber density (IENFD) the gold standard for small-fiber neuropathy has not been evaluated.

Objective
We assessed the IENFD, pain symptoms and quality of life (QoL) with MIRE therapy compared to placebo in painful DPN.

Material and Methods
Participants with type 2 diabetes and painful DPN were randomized to receive MIRE or sham therapy dosed thrice a week for 12 weeks. Quantitative assessment of IENFD was performed from 3 mm skin punch-biopsy specimens at baseline and after 12 weeks. We also assessed the QoL with Norfolk QOL, symptom severity with visual analogue scale (VAS), and neuropathy assessment with Michigan neuropathy severity instrument and neuropathy disability score.

Results
Thirty-eight participants were enrolled and 30 completed the study protocol. The mean age of participants in MIRE cohort was 59.1 ± 9.2 years, duration of diabetes 12.9 ± 3.1 years, and symptom duration of 3.9 ± 3.7 months. The mean IENFD was 0.90 ± 0.73/mm2 (P < 0.01) and 1.71 ± 1.11/mm2 in the MIRE cohort and 0.60 ± 0.89/mm2 and 2.17 ± 0.98/mm2 (P < 0.01) in sham cohort at baseline and after 3 months. The median decline in VAS was 5.1 (4.0-7.6) and 3.0 (0.4-5.6) points (intergroup difference, P = 0.01); and an increase in Norfolk QoL-DN by 15 (11-18) and 4 (4-14.2) points (intergroup difference, P = 0.021) in MIRE and sham cohort, respectively after 3 months.

Conclusions
MIRE therapy does not increase IENFD over short-term usage. However, MIRE therapy provides symptomatic benefit and improves QoL in patients with painful DPN.

Rastogi|Ashu|A| Uppula|Pavan|P| Saikia|Uma|U| Bhansali|Anil|A|

D000368:Aged
D003924:Diabetes Mellitus, Type 2
D003929:Diabetic Neuropathies
D006801:Humans
D008875:Middle Aged
D009412:Nerve Fibers
D010147:Pain Measurement
D011788:Quality of Life

Diabetic neuropathy
intraepidermal nerve-fiber density
neuropathic pain
norfolk quality of life
visual analog scale


Diclazuril Inhibits Biofilm Formation and Hemolysis of Staphylococcus aureus.

Abstract: Biofilm formation and hemolysis induced by Staphylococcus aureus are closely related to pathogenicity. However, no drugs exist to inhibit biofilm formation or hemolysis induced by S. aureus in clinical practice. This study found diclazuril had antibacterial action against S. aureus with minimum inhibitory concentrations (MICs) at 50 μM for both methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA). Diclazuril (at 1/4× or 1/8× MICs) significantly inhibited biofilm formation of S. aureus under static or flow-based conditions and also inhibited hemolysis induced by S. aureus. The RNA levels of transcriptional regulatory genes (agrA, agrC, luxS, sarA, sigB, saeR, saeS), biofilm formation-related genes (aur, bap, ccpA, cidA, clfA, clfB, fnbA, fnbB, icaA, icaB, sasG), and virulence-related genes (hla, hlb, hld, hlg, lukDE, lukpvl-S, spa, sbi, alpha-3 PSM, beta PSM, coa) of S. aureus were decreased when treated by diclazuril (at 1/4× MIC) for 4 h. The diclazuril nonsensitive clones of S. aureus were selected in vitro by induction of wildtype strains for about 90 days under the pressure of diclazuril. Mutations in the possible target genes of diclazuril against S. aureus were detected by whole-genome sequencing. This study indicated that there were three amino acid mutations in the diclazuril nonsensitive clone of S. aureus, two of which were located in genes with known function (SMC-Scp complex subunit ScpB and glyceraldehyde-3-phosphate dehydrogenase 1, respectively) and one in a gene with unknown function (hypothetical protein). Diclazuril showed a strong inhibition effect on planktonic cells and biofilm formation of S. aureus with the overexpression of the scpB gene.

Zheng|Jinxin|J|0000-0003-4064-2430 Shang|Yongpeng|Y| Wu|Yang|Y| Wu|Jianfeng|J|0000-0002-9770-5538 Chen|Junwen|J| Wang|Zhanwen|Z| Sun|Xiang|X| Xu|Guangjian|G| Deng|Qiwen|Q| Qu|Di|D| Yu|Zhijian|Z|

diclazuril
biofilm
hemolysis
Staphylococcus aureus
virulence


Targeted Intracellular Controlled Drug Delivery and Tumor Therapy through in Situ Forming Ag Nanogates on Mesoporous Silica Nanocontainers.

Abstract: Targeting nanocontainers to the pathological zone and controlling release of their cargoes, in particular delivery of anticancer drugs to specific tumor cells in a targeted and controlled manner, remain the key challenges in drug delivery. This paper reports the development of a traceable and tumor-targeted intracellular drug release nanocontainer. The nanocontainer is obtained by in situ growth of silver nanoparticles (AgNPs) on the surfaces of mesoporous silica nanospheres (MSNs) using a DNA-templated process. Additionally, drug release from the nanopores is achieved by selective glutathione (GSH)-triggered dismantle of the AgNPs, and the concurrent fluorescence change allows real-time monitoring of drug release efficacy and facile visualization of in vivo delivery events. After being functionalized with sgc8 aptamer on the outer shell of the AgNPs, the targeted nanocontainers are delivered into acute lymphoblastic leukemia cells by aptamer-mediated recognition and endocytosis. Moreover, the GSH-responsive process presents an improvement in the cell-specific drug release and chemotherapeutic inhibition of tumor growth.

Liu|Changhui|C| Zheng|Jing|J| Deng|Li|L| Ma|Cheng|C| Li|Jishan|J| Li|Yinhui|Y| Yang|Sheng|S| Yang|Jinfeng|J| Wang|Jing|J| Yang|Ronghua|R|

D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma

drug delivery
glutathione
DNA
mesoporous silica nanoparticle
silver sphere