Unveiling microbial structures during raw microalgae digestion and co-digestion with primary sludge to produce biogas using semi-continuous AnMBR systems.

Abstract: Methane production from microalgae can be enhanced through anaerobic co-digestion with carbon-rich substrates and thus mitigate the inhibition risk associated with its low C:N ratio. Acclimated microbial communities for microalgae disruption can be used as a source of natural enzymes in bioenergy production. However, co-substrates with a certain microbial diversity such as primary sludge might shift the microbial structure. Substrates were generated in a Water Resource Recovery Facility (WRRF) and combined as follows: Scenedesmus or Chlorella digestion and microalgae co-digestion with primary sludge. The study was performed using two lab-scale Anaerobic Membrane Bioreactors (AnMBR). During three years, different feedstocks scenarios for methane production were evaluated with a special focus on the microbial diversity of the AnMBR. 57% of the population was shared between the different feedstock scenarios, revealing the importance of Anaerolineaceae members besides Smithella and Methanosaeta genera. The addition of primary sludge enhanced the microbial diversity of the system during both Chlorella and Scenedesmus co-digestion and promoted different microbial structures. Aceticlastic methanogen Methanosaeta was dominant in all the feedstock scenarios. A more remarkable role of syntrophic fatty acid degraders (Smithella, Syntrophobacteraceae) was observed during co-digestion when only microalgae were digested. However, no significant changes were observed in the microbial composition during anaerobic microalgae digestion when feeding only Chlorella or Scenedesmus. This is the first work revealing the composition of complex communities for semi-continuous bioenergy production from WRRF streams. The stability and maintenance of a microbial core over-time in semi-continuous AnMBRs is here shown supporting their future application in full-scale systems for raw microalgae digestion or co-digestion.

Zamorano-López|N|N| Borrás|L|L| Seco|A|A| Aguado|D|D|

Microalgae
Co-digestion
Biogas
AnMBR
16S rRNA gene
Anaerobic digestion


Transfer Learning Strategy Based on Unsupervised Learning and Ensemble Learning for Breast Cancer Molecular Subtype Prediction Using Dynamic Contrast-Enhanced MRI.

Abstract:
BACKGROUND
Imaging-driven deep learning strategies focus on training from scratch and transfer learning. However, the performance of training from scratch is often impeded by the lack of large-scale labeled training data. Additionally, owing to the differences between source and target domains, analyzing medical image tasks satisfactorily via transfer learning based on ImageNet is difficult.

PURPOSE
To investigate two transfer learning algorithms for breast cancer molecular subtype prediction (luminal and non-luminal) based on unsupervised pre-training and ensemble learning: M_EL and B_EL, using malignant and benign datasets as the source domain, respectively.

STUDY TYPE
Retrospective.

POPULATION
Eight hundred and thirty-three female patients with histologically confirmed breast lesions (567 benign and 266 malignant cases) were selected. In the 5-fold cross-validation, the malignant cohort was randomly divided into 5 subsets to form a training set (80%) and a validation set (20%).

FIELD STRENGTH/SEQUENCE
3.0 T, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using T1-weighted high-resolution isotropic volume examination.

ASSESSMENT
First, three datasets acquired at different times post-contrast were preprocessed as unlabeled source domains. Second, three baseline networks corresponding to the different MRI post-contrast phases were built, optimized by a combination of mutual information maximization between high- and low-level representations and prior distribution constraints. Next, the pre-trained networks were fine-tuned on the labeled target domain. Finally, prediction results were integrated using weighted voting-based ensemble learning.

STATISTICAL TESTS
Mean accuracy, precision, specificity, and area under receiver operating characteristic curve (AUC) were obtained with 5-fold cross-validation. P < 0.05 was considered to be statistically significant.

RESULTS
Compared with a convolutional long short-term memory network, pre-trained VGG-16, VGG-19, and DenseNet-121 from ImageNet, M_EL and B_EL exhibited significantly more optimized prediction performance (specificity: 90.5% and 89.9%; accuracy: 82.6% and 81.1%; precision: 91.2% and 90.9%; AUC: 0.836 and 0.823, respectively).

DATA CONCLUSION
Transfer learning based on unsupervised pre-training may facilitate automatic prediction of breast cancer molecular subtypes.

LEVEL OF EVIDENCE
3 TECHNICAL EFFICACY: Stage 2.

transfer learning
unsupervised learning
molecular subtype
artificial intelligence
breast MRI
deep mutual information maximization


High-grade salivary gland carcinoma with the ETV6-NTRK3 gene fusion: A case report and literature review of secretory carcinoma with high-grade transformation.

Abstract: Secretory carcinoma or mammary analog secretory carcinoma is an entity of salivary gland carcinoma that is characterized by the ETV6-NTRK3 gene fusion. Although it is generally considered to be a low-grade malignancy, some cases of secretory carcinoma with high-grade transformation (SCHG) have been reported. We herein describe a case of SCHG composed almost exclusively of the high-grade component. The patient presented with a growing mass in the buccal mucosa and underwent surgery. Tumor cells showing high-grade nuclear atypia were arranged in solid or cribriform nests with comedo-like necrosis. A differential diagnosis included high-grade salivary gland carcinoma, such as salivary duct carcinoma. Immunohistochemically, tumor cells were focally positive for S-100 and negative for mammaglobin and showed nuclear positivity for pan-Trk. A reverse transcription polymerase chain reaction assay showed that the tumor harbored the ETV6-NTRK3 gene fusion. A histological review of microscopic slides of the tumor did not reveal a typical secretory carcinoma component, except for a very focal area. We ultimately diagnosed this tumor as SCHG. This case underscores the importance of recognizing the histological spectrum of SCHG and the utility of pan-Trk immunohistochemistry to detect secretory carcinoma, which may be targeted by tyrosine kinase inhibitors.

salivary gland carcinoma
ETV6-NTRK3
secretory carcinoma
high-grade transformation
pan-Trk


Endoplasmic reticulum stress in bipolar disorder? - BiP and CHOP gene expression- and XBP1 splicing analysis in peripheral blood.

Abstract:
BACKGROUND
Endoplasmic Reticulum stress activates the Unfolded Protein Response, which is partially impaired in Bipolar Disorder (BD) according to previous in-vitro studies. Thus, BiP and CHOP gene expression and XBP1 splicing were analyzed in peripheral blood of study participants with BD and controls.

METHODS
RNA was isolated from fasting blood of study participants with BD (n = 81) and controls (n = 54) and reverse transcribed into cDNA. BiP and CHOP gene expression was analyzed with quantitative RT-PCR. Atypical splicing of XBP1 mRNA was measured by semi-quantitative RT-PCR, gel-electrophoresis and densitometry. ANCOVAs with the covariates age, BMI, sex, lithium and anticonvulsants intake were used with SPSS. Bonferroni correction was used to correct for multiple testing (adjusted p = 0.0083).

RESULTS
BiP gene expression was significantly higher in BD than in controls (F(1/128) = 10.076, p = 0.002, Partial η2 = 0.073). Total XBP1 (F(1/126) = 9.550, p = 0.002, Partial η2 = 0.070) and unspliced XBP1 (F(1/128)= 8.803, p= 0.004, Patial η2 = 0.065) were significantly decreased in BD. Spliced XBP1 (F(1/126) = 5.848, p = 0.017, Partial η2 = 0.044) and the ratio spliced XBP1/ unspliced XBP1 did not differ between BD and controls (F(1/126) = 0.599, p = 0.441, Partial η2 = 0.005). Gene expression did not differ between euthymia, depression and mania.

DISCUSSION
BiP gene expression was significantly higher in BD compared to controls. Total and unspliced XBP1 were significantly lower in BD than in the control group. Thus, both genes may be considered as putative trait markers. Nevertheless, XBP1 splicing itself did not differ between both groups.

Bengesser|Susanne A|SA|
Reininghaus|Eva Z|EZ|
Dalkner|Nina|N|
Birner|Armin|A|
Hohenberger|Helena|H|
Queissner|Robert|R|
Fellendorf|Frederike|F|
Platzer|Martina|M|
Pilz|Rene|R|
Hamm|Carlo|C|
Rieger|Alexandra|A|
Kapfhammer|Hans-Peter|HP|
Mangge|Harald|H|
Reininghaus|Bernd|B|
Meier-Allard|Nathalie|N|
Stracke|Anika|A|
Fuchs|Robert|R|
Holasek|Sandra|S|

D000091342:Endoplasmic Reticulum Chaperone BiP

Endoplasmic Reticulum
Bipolar Disorder
BiP
CHOP
XBP1
Unfolded Protein Response
ER stress
GRP78


Treatable Cause of Pancytopenia, Recurrent Infections and Refractory Epilepsy: Secondary to Hereditary Folate Malabsorption (HFM) Due to Novel Pathogenic Variant.

Abstract: Hereditary folate malabsorption (HFM) is a rare disorder of proton-coupled folate transporter deficiency. It is characterized by macrocytic anemia, recurrent infections, and epilepsy. A five-year-old girl presented with recurrent pneumonia, diarrhea, and mouth ulcers. On examination, pallor, microcephaly with spastic quadriparesis was noted. On investigations, leukopenia and thrombocytopenia with megaloblastic bone marrow picture and low folate levels was found. HFM was diagnosed at two years of age and the child was treated with folinic acid. Her diagnosis was confirmed by whole-exome sequencing which revealed a novel pathogenic homozygous frameshift insertion variation (c.620dupG) in the exon 2 of the SLC46A1 gene which was further confirmed by Sanger sequencing. The child improved significantly except for a partial improvement in neurological symptoms.

Hereditary folate malabsorption
Macrocytic anemia
Folinic acid
SLC46A1 gene
Intracranial calcification


Single-nucleus transcriptomic landscape of primate hippocampal aging.

Abstract: The hippocampus plays a crucial role in learning and memory, and its progressive deterioration with age is functionally linked to a variety of human neurodegenerative diseases. Yet a systematic profiling of the aging effects on various hippocampal cell types in primates is still missing. Here, we reported a variety of new aging-associated phenotypic changes of the primate hippocampus. These include, in particular, increased DNA damage and heterochromatin erosion with time, alongside loss of proteostasis and elevated inflammation. To understand their cellular and molecular causes, we established the first single-nucleus transcriptomic atlas of primate hippocampal aging. Among the 12 identified cell types, neural transiently amplifying progenitor cell (TAPC) and microglia were most affected by aging. In-depth dissection of gene-expression dynamics revealed impaired TAPC division and compromised neuronal function along the neurogenesis trajectory; additionally elevated pro-inflammatory responses in the aged microglia and oligodendrocyte, as well as dysregulated coagulation pathways in the aged endothelial cells may contribute to a hostile microenvironment for neurogenesis. This rich resource for understanding primate hippocampal aging may provide potential diagnostic biomarkers and therapeutic interventions against age-related neurodegenerative diseases.

Zhang|Hui|H|
Li|Jiaming|J|
Ren|Jie|J|0000-0002-6450-3163
Sun|Shuhui|S|
Ma|Shuai|S|
Zhang|Weiqi|W|0000-0002-8885-5104
Yu|Yang|Y|
Cai|Yusheng|Y|
Yan|Kaowen|K|
Li|Wei|W|
Hu|Baoyang|B|
Chan|Piu|P|
Zhao|Guo-Guang|GG|
Belmonte|Juan Carlos Izpisua|JCI|
Zhou|Qi|Q|
Qu|Jing|J|0000-0002-3988-5067
Wang|Si|S|0000-0003-2431-0612
Liu|Guang-Hui|GH|0000-0001-9289-8177

primate
aging
hippocampus
single-cell RNA sequencing


Providing a Placental Transfusion in Newborns Who Need Resuscitation.

Abstract: Over the past decade, there have been several studies and reviews on the importance of providing a placental transfusion to the newborn. Allowing a placental transfusion to occur by delaying the clamping of the umbilical cord is an extremely effective method of enhancing arterial oxygen content, increasing cardiac output, and improving oxygen delivery. However, premature and term newborns who require resuscitation have impaired transitional hemodynamics and may warrant different methods to actively provide a placental transfusion while still allowing for resuscitation. In this review, we will provide evidence for providing a placental transfusion in these circumstances and methods for implementation. Several factors including cord clamping time, uterine contractions, umbilical blood flow, respirations, and gravity play an important role in determining placental transfusion volumes. Finally, while many practitioners agree that a placental transfusion is beneficial, it is not always straightforward to implement and can be performed using different methods, making this basic procedure important to discuss. We will review three placental transfusion techniques: delayed cord clamping, intact umbilical cord milking, and cut-umbilical cord milking. We will also review resuscitation with an intact cord and the evidence in term and preterm newborns supporting this practice. We will discuss perceived risks versus benefits of these procedures. Finally, we will provide key straightforward concepts and implementation strategies to ensure that placental-to-newborn transfusion can become routine practice at any institution.

Katheria|Anup C|AC|
Brown|Melissa K|MK|
Rich|Wade|W|
Arnell|Kathy|K|

placental transfusion
resuscitation
delayed cord clamping
cord milking
blood volume
hypovolemia
neonatal transition
perfusion


Combination of Cetuximab and Oncolytic Virus Canerpaturev Synergistically Inhibits Human Colorectal Cancer Growth.

Abstract: The naturally occurring oncolytic herpes simplex virus canerpaturev (C-REV), formerly HF10, proved its therapeutic efficacy and safety in multiple clinical trials against melanoma, pancreatic, breast, and head and neck cancers. Meanwhile, patients with colorectal cancer, which has increased in prevalence in recent decades, continue to have poor prognosis and morbidity. Combination therapy has better response rates than monotherapy. Hence, we investigated the antitumor efficacy of cetuximab, a widely used anti-epidermal growth factor receptor (EGFR) monoclonal antibody, and C-REV, either alone or in combination, in vitro and in an in vivo human colorectal xenograft model. In human colorectal cancer cell lines with different levels of EGFR expression (HT-29, WiDr, and CW2), C-REV exhibited cytotoxic effects in a time- and dose-dependent manner, irrespective of EGFR expression. Moreover, cetuximab had no effect on viral replication in vitro. Combining cetuximab and C-REV induced a synergistic antitumor effect in HT-29 tumor xenograft models by promoting the distribution of C-REV throughout the tumor and suppressing angiogenesis. Application of cetuximab prior to C-REV yielded better tumor regression than administration of the drug after the virus. Thus, cetuximab represents an ideal virus-associated agent for antitumor therapy, and combination therapy represents a promising antitumor strategy for human colorectal cancer.

Wu|Zhiwen|Z|
Ichinose|Toru|T|
Naoe|Yoshinori|Y|
Matsumura|Shigeru|S|
Villalobos|Itzel Bustos|IB|
Eissa|Ibrahim Ragab|IR|
Yamada|Suguru|S|
Miyajima|Noriyuki|N|
Morimoto|Daishi|D|
Mukoyama|Nobuaki|N|
Nishikawa|Yoko|Y|
Koide|Yusuke|Y|
Kodera|Yasuhiro|Y|
Tanaka|Maki|M|
Kasuya|Hideki|H|

cetuximab
human colorectal cancer
C-REV
HSV
oncolytic herpes virus HF10


Physicochemical characteristics and phytochemical profiles of yellow and red Physalis (Physalis alkekengi L. and P. pubescens L.) fruits cultivated in China.

Abstract: Physicochemical characteristics and phytochemical profiles of red (Physalis alkekengi L., RP) and yellow (P. pubescens L., YP) Physalis fruits cultivated in three provinces of China were characterized. YP fruits showed significantly lower levels of total organic acids and elevated total sugars than those of RP. A total of 18 compounds was tentatively identified in hydromethanolic extracts of Physalis fruits applying HPLC-DAD-ESI-MSn and HR-ESI-MS. Cinnamoyl and hydroxycinnamoyl conjugates prevailed in both fruits. Diverse mono- and dihexosides of cinnamic, coumaric, caffeic, ferulic, and sinapic acid were found in YP, while RP merely contained feruloyl and sinapoyl hexosides. N,N´-dicaffeoylspermidine isomers were found in YP fruits, whereas N,N´-bis(dihydrocaffeoyl)spermine was exclusively detected in two of the RP samples. Additionally, two HDMF (4-hydroxy-2,5-dimethyl-3(2H)-furanone) hexosides were tentatively identified for the first time in YP. Both RP and YP fruits collected from three different provinces in China showed a significant intraspecific variability regarding their phytochemical profiles, despite their similar morphological fruit traits.

Wen|Xin|X|
Erşan|Sevcan|S|
Li|Mo|M|
Wang|Kunli|K|
Steingass|Christof Björn|CB|
Schweiggert|Ralf Martin|RM|
Ni|Yuanying|Y|
Carle|Reinhold|R|

D002851:Chromatography, High Pressure Liquid

Physalis
Organic acids
Sugars
Furanones
Phenolic compounds
Solanaceae


Discrepancies regarding the quality of life of patients with Alzheimer's disease: a three-year longitudinal study.

Abstract: Cross-sectional studies report notable discrepancies between patient and caregiver ratings of the quality of life of patients (QoL-p) with Alzheimer's disease (AD). This study aimed to identify the factors associated with any changes in QoL-p ratings and any discrepancies between patient and caregiver ratings of QoL-p. Three-year follow-up of a cohort of non-institutionalized patients (n = 119). QoL-p was assessed by the Quality of Life in AD (QoL-AD) scale. We analyzed the influence of functional and cognitive status and behavioral problems in patients, and burden and mental health in caregivers. Repeated measures analysis was applied to the scores of patients and caregivers on the QoL-AD, and to the discrepancies between them. Generally, patients' own ratings remained stable over time (F3,116 = 0.9, p = 0.439), whereas caregiver ratings showed a decline (F3,116 = 9.4, p < 0.001). In the analysis of discrepancies, patients with anosognosia gave higher ratings (F1,117 = 11.9, p = 0.001), whereas caregiver ratings were lower when the patient showed greater agitation (F1,117 = 13.0, p < 0.001), apathy (F1,117 = 15.4, p < 0.001), and disabilities (F1,117 = 17.1, p < 0.001), and when the caregiver experienced greater burden (F1,117 = 9.0, p = 0.003) and worse mental health (F1,117 = 10.1, p = 0.003). Patient ratings of QoL-p remain generally stable over time, whereas those of caregivers show a decline, there being significant discrepancies in relation to specific patient and caregiver factors.

Conde-Sala|Josep L|JL|
Turró-Garriga|Oriol|O|
Garre-Olmo|Josep|J|
Vilalta-Franch|Joan|J|
Lopez-Pousa|Secundino|S|

D011569:Psychiatric Status Rating Scales

quality of life
patients
Alzheimer's disease
longitudinal study
caregivers
mental health
anosognosia
disabilities
caregiver burden
neuropsychiatric symptoms


The immune response to a two-dose schedule of quadrivalent HPV vaccine in 9-13 year-old girls: Is it influenced by age, menarche status or body mass index?

Abstract: HPV vaccines are highly immunogenic. A two-dose schedule for 9-14 year-old is recommended. However, no data exist regarding the impact of age, menarche status and body mass index (BMI) on the immune response to a two-dose schedule. In this post-hoc analysis, we present antibody titers to HPV6/11/16/18 in 9-13 year-old girls participating in a randomized clinical trial and assigned to receive two doses of quadrivalent HPV vaccine at 6 months interval (NCT00501137). Antibody titers were measured at month 7 and 24 of the study by using a competitive Luminex immunoassay (cLIA).Both, at Month 7 and 24 the GMTs for four HPV genotypes were similar across the age bands, and did not vary significantly by menarche status. Overweight and obese girls had lower GMTs. More than 99% of girls remained seropositive for HPV 6/11/16 and 89% for HPV18 at month 24. Comprehensive data in overweight and obese vaccines are warranted.

Sauvageau|Chantal|C|
Gilca|Vladimir|V|
Donken|Robine|R|
Fan|Shu Yu|SY|
Ogilvie|Gina|G|
Dobson|Simon|S|

D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18

Two-dose
Vaccine
Immunogenicity
Human Papillomavirus


Comparative study of suction drainage placement in cementless hip replacement among patients undergoing extended thromboprophylaxis: a prospective randomized study.

Abstract:
BACKGROUND
The use of drains reportedly does not improve surgical outcomes after hip replacement. There is still a lack of strict recommendations for drain placement after primary hip replacement. This study aimed to assess the safety of not using suction drainage after primary hip replacement in a population of patients undergoing extended thromboprophylaxis.

METHODS
In this prospective randomized study, all patients were qualified for primary hip replacement and were divided into two groups: with and without drainage. The inclusion criterion was idiopathic hip osteoarthritis. The exclusion criteria were secondary coxarthrosis, autoimmune disease, coagulopathy, venous/arterial thrombosis, hepatic/renal insufficiency, cement, or hybrid endoprostheses. We performed an intention-to-treat analysis. Clinical, laboratory, and radiographic parameters were measured for the first three days after surgery. Hematoma collection, due to extended thromboprophylaxis, in the joint and soft tissues was evaluated precisely. The patients underwent follow-up for 30 days.

RESULTS
The final analysis included a total of 100 patients. We did not find any significant statistical differences between groups in terms of hip fluid collection (9.76 vs. 10.33 mm, with and without drainage, respectively; mean difference, 0.6 mm; 95 % confidence interval [CI] -2.8 to 3.9; p = 0.653), estimated blood loss (1126 vs. 1224 ml; mean difference, 97.1 ml; 95 % CI -84.1 to 278.2; p = 0.59), and hemoglobin levels on postoperative day 3 (11.05 vs. 10.85 g/dl; mean difference, 0.2; 95 % CI -2.1 to 2.5; p = 0.53). In addition, the other parameters did not show significant differences between groups. Notably, two cases of early infections were observed in the no-drainage group, whereas there were no such complications in the drainage group.

CONCLUSIONS
We conclude that the use of closed suction drainage after primary hip replacement is a safe procedure in patients undergoing extended thromboprophylaxis. Further research is warranted to validate these findings.

TRIAL REGISTRATION
The study was successfully registered retrospectively at Clinicaltrial.gov with the identification number NCT04333264  03 April 2020.

Suction drainage
Cementless hip replacement
Surgical outcomes
Hematoma


Pernicious Anemia Presenting With Pseudo Thrombotic Microangiopathy and Falsely Elevated B 12 Levels.

Abstract: Pseudo thrombotic microangiopathy is a distinct clinical entity that is seen in patients with B12 deficiency. We describe a patient who presented with microangiopathic hemolytic anemia, thrombocytopenia, altered mentation and renal insufficiency. Thrombotic thrombocytopenic purpura was a major concern; however the peripheral blood smear showed hypersegmented neutrophils and the altered mental status as well as renal dysfunction improved with red cell transfusions. It was concluded that her clinical picture was more consistent with ineffective erythropoiesis, which can mimic thrombotic thrombocytopenic purpura (TTP). She was ultimately diagnosed with pernicious anemia based on positive intrinsic factor antibody, elevated methylmalonic acid, and homocysteine levels. Her B12 levels were falsely elevated which confounded the diagnosis. Distinguishing between these two conditions is imperative to avoid unwarranted plasmapheresis.

Katiyar|Vatsala|V| Qian|Edward|E| Vohra|Ishaan|I| Sleiman|Jose|J| Rubinstein|Paul|P|

Pernicious anemia
Pseudo thrombotic microangiopathy
B12 deficiency
TTP
False elevated B12 levels


3D printing for preoperative planning and surgical training: a review.

Abstract: Surgeons typically rely on their past training and experiences as well as visual aids from medical imaging techniques such as magnetic resonance imaging (MRI) or computed tomography (CT) for the planning of surgical processes. Often, due to the anatomical complexity of the surgery site, two dimensional or virtual images are not sufficient to successfully convey the structural details. For such scenarios, a 3D printed model of the patient's anatomy enables personalized preoperative planning. This paper reviews critical aspects of 3D printing for preoperative planning and surgical training, starting with an overview of the process-flow and 3D printing techniques, followed by their applications spanning across multiple organ systems in the human body. State of the art in these technologies are described along with a discussion of current limitations and future opportunities.

Ganguli|Anurup|A|
Pagan-Diaz|Gelson J|GJ|
Grant|Lauren|L|
Cvetkovic|Caroline|C|
Bramlet|Mathew|M|
Vozenilek|John|J|
Kesavadas|Thenkurussi|T|
Bashir|Rashid|R|

3D printing
Preoperative planning
Surgical training
Organ models
Rapid prototyping


The Exceptional Diversity of Homoleptic Uranium-Methyl Complexes.

Abstract: Homoleptic σ-bonded uranium-alkyl complexes have been a synthetic target since the Manhattan Project. The current study describes the synthesis and characterization of several unprecedented uranium-methyl complexes. Amongst these complexes, the first example of a homoleptic uranium-alkyl dimer, [Li(THF)4 ]2 [U2 (CH3 )10 ], as well as a seven-coordinate uranium-methyl monomer, {Li(OEt2 )Li(OEt2 )2 UMe7 Li}n were both crystallographically identified. The diversity of complexes reported herein provides critical insight into the structural diversity, electronic structure and bonding in uranium-alkyl chemistry.

homoleptic complexes
organometallic compounds
uranium


Chronic Traumatic Encephalopathy in Athletes Involved with High-impact Sports.

Abstract:
BACKGROUND AND PURPOSE
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease occurring most commonly in athletes and is caused by repeated concussive or subconcussive blows to the head. The main purpose of this review is to evaluate the published literature on chronic traumatic encephalopathy (CTE) in athletes participating in high-impact sports. In particular, we highlight the significance of concussive and subconcussive impacts in multiple sports, elucidate the differences between clinical/pathological features of CTE and related neurodegenerative diseases, and provide an explanation for the variation in clinical presentation between athletes of different sports.

METHODS
A review targeting relevant publications to CTE was performed. The PubMed/MEDLINE index was searched for keywords such as "chronic traumatic encephalopathy," "repetitive traumatic brain injury," "mild traumatic brain injury," and "concussion" from year 1924 through March 1, 2016.

RESULTS
A consensus panel's recent identification of a pathognomonic pathology in CTE, characterized by an irregular distribution of phosphorylated tau deposits, is an important step in developing consensus diagnostic criteria and clinicopathological studies. After review of major clinical studies, evidence suggests that there are clear differences in neuropathological features, clinical progression, and manifestation of symptoms between CTE and other neurodegenerative diseases. The literature suggests boxers tend to have more severe symptoms than other athletes due to more frequent rotational and shearing impacts. Data regarding genetic predispositions of CTE have been inconsistent in part due to low subject populations. Positron emission tomography imaging involving tau-binding ligands has recently proven effective in differentiating CTE from control groups and other neurodegenerative diseases.

CONCLUSIONS
Further longitudinal studies should be conducted to correlate the number of suffered concussive/subconcussive forces to the likelihood of developing chronic traumatic brain injury symptoms. Research striving for a reliable antemortem CTE diagnosis would be immensely beneficial, leading to more accurate estimates of prevalence, allowing clinicians to assess future risk of athletes' continued participation in sports, and enabling clinicians to make appropriate preventive recommendations.

Safinia|Cyrus|C|
Bershad|Eric M|EM|
Clark|H Brent|HB|
SantaCruz|Karen|K|
Alakbarova|Naila|N|
Suarez|Jose I|JI|
Divani|Afshin A|AA|

Chronic traumatic encephalopathy
concussion
pathology
traumatic brain injury
brain injury
neurological injury


Towards a comprehensive understanding of the Si(100)-2×1 surface termination through hydrogen passivation using methylamine and methanol: a theoretical approach.

Abstract: Using density functional theory, we explored the termination process of Si (100)-2 × 1 reconstructed surface mechanistically through the dehydrogenation of small molecules, considering methyl amine and methanol as terminating reagents. At first, both the terminating reagents form two types of adduct through adsorption on the Si (100)-2 × 1 surface, one in chemisorption mode and the other via physisorption, from which the dehydrogenation process is initiated. By analyzing the activation barriers, it was observed that termination of the Si-surface through the dehydrogenation is kinetically almost equally feasible using either reagent. We further examined in detail the mechanism for each termination process by analyzing geometrical parameters and natural population analysis charges. From bonding evaluation, it is evident that hydrogen abstraction from adsorbates on the Si-surface is asymmetric in nature, where one hydrogen is abstracted as hydride by the electrophilic surface Si and the other hydrogen is abstracted as proton by the neucleophilic surface Si. Moreover, it was also observed that hydride transfer from adsorbate to the Si-surface occurs first followed by proton transfer. Overall, our theoretical interpretation provides a mechanistic understanding of the Si (100)-2 × 1 reconstructed surface termination by amine and alcohol that will further motivate researchers to design different types of decorated semiconductor devices. Graphical Abstract Surface termination process of Si(100)-2×1 through formation of non-polar Si-H bonds via dehydrogenation of methylamine and methanol as terminating reagents.

Debnath|Tanay|T|
Ash|Tamalika|T|
Sarkar|Subhendu|S|
Das|Abhijit Kr|AK|

Surface termination
Dehydrogenation
Bonding evaluation
Potential energy surface
Si(100)-2 × 1 reconstructed surface


Photoreflectance/scattering measurements of spider silks informed by standard optics.

Abstract: The silks of certain orb weaving spiders are emerging as high-quality optical materials. This motivates study of the optical properties of such silk and particularly the comparative optical properties of the silks of different species. Any differences in optical properties may impart biological advantage for a spider species and make the silks interesting for biomimetic prospecting as optical materials. A prior study of the reflectance of spider silks from 18 species reported results for three species of modern orb weaving spiders (Nephila clavipes, Argiope argentata and Micrathena Schreibersi) as having reduced reflectance in the UV range. (Modern in the context used here means more recently derived.) The reduced UV reflectance was interpreted as an adaptive advantage in making the silks less visible to insects. Herein, a standard, experimental technique for measuring the reflectance spectrum of diffuse surfaces, using commercially available equipment, has been applied to samples of the silks of four modern species of orb weaving spiders: Phonognatha graeffei, Eriophora transmarina, Nephila plumipes and Argiope keyserlingi. This is a different technique than used in the previous study. Three of the four silks measured have a reduced signal in the UV. By taking the form of the silks as optical elements into account, it is shown that this is attributable to a combination of wavelength-dependent absorption and scattering by the silks rather than differences in reflectance for the different silks. Phonognatha graeffei dragline silk emerges as a very interesting spider silk with a flat 'reflectance'/scattering spectrum which may indicate it is a low UV absorbing dielectric micro-fibre. Overall the measurement emerges as having the potential to compare the large numbers of silks from different species to prospect for those which have desirable optical properties.

scattering
spider silk
reflectance
absorption
dragline


Effects of post-weaning diet on metabolic parameters and DNA methylation status of the cryptic promoter in the A(vy) allele of viable yellow mice.

Abstract: Mice carrying the A(vy) allele are epigenetic mosaics. If the majority of cells have an active (demethylated) intracisternal A particle (IAP), mice have a yellow coat color and develop adult-onset obesity and diabetes, while mice whose mosaicism predominantly reflects an inactive (methylated) IAP are pseudoagouti (brown) and less prone to metabolic disease. Brown and yellow coat color A(vy)/a post-weaning mice were placed on one of three diets [AIN, and two lower-calorie diets National Institutes of Health (NIH) and methyl-supplemented, NIHMe] to determine whether coat color, weight gain, blood glucose and methylation of hepatic IAP became altered. None of the diets altered A(vy)/a mice coat color. NIHMe did not protect against increasing obesity or the usual onset of hyperglycemia in males. Nor did it promote increased methylation of A(vy) IAP in liver tissue. By contrast, AIN, despite its higher content of fat and carbohydrate and ability to promote greater weight gains than the NIH and NIHMe diets, protected males better against hyperglycemia than either the NIH or NIHMe diets. This diet led to a significantly reduced (~50%; P = .003) average methylation state of all CpG sites within the hepatic IAP for the pseudoagouti mice. On AIN, but not on the other diets, extent of hepatic IAP methylation was negatively correlated (R = 0.97, P ≤ .001) with body weight of pseudoagouti mice. The findings indicate that post-weaning diet might influence interpretation of studies with A(vy)/a mice because IAP methylation patterns may be malleable in certain organs and influenced by post-weaning diet.

Warzak|Denise A|DA|
Johnson|Sarah A|SA|
Ellersieck|Mark R|MR|
Roberts|R Michael|RM|
Zhang|Xiang|X|
Ho|Shuk-Mei|SM|
Rosenfeld|Cheryl S|CS|

DNA methylation
Epigenetics
Obesity
Hyperglycemia
Agouti
Methyl diet


Peritonitis Following Duodenal Ulcer Perforation in a Newborn: A Case Report.

Abstract: Duodenal ulcer is an uncommon condition in children, that is why it is not usually considered as the differential diagnosis unless it presents with complications including perforation and haemorrhage. Moreover, duodenal ulcer perforation is an uncommon entity in paediatric age group. Early diagnosis and treatment is crucial in order to improve survival. A three-day-old male neonate was admitted to our hospital because of abdominal distension. The neonate was lethargic. He underwent laparotomy. There was a perforated ulcer, 5×5mm in size, on the anterior aspect of the first part of the duodenum. The perforated ulcer was closed with a single layer. Six-month follow-up revealed no abnormality.

Amouei|Abdolhamid|A|
Ehsani|Fatemeh|F|
Zarch|Mojtaba Babaei|MB|
Tabatabaei|Seyed Mostafa|SM|
Ghodratipour|Zahra|Z|

Neonate
Abdominal distension
Peptic ulcer


The dynamic changes in the pattern of liver function tests in pregnant obese women.

Abstract: Obesity is an important problem in healthcare regarding gestating women. The objective of the present study was to highlight the impact that obesity has on the hepatic function in pregnant women by comparing the functional tests used in current practice. In addition, the aim was to identify possible predictors of liver damage by analyzing specific anthropometric data. The present study was descriptive, observational, retrospective, and based on the observation sheets found in the database of the Institute for the Health of the Mother and Child, the Obstetrics Gynecology Department of Polizu Hospital. Patients who presented for consultation in each trimester of pregnancy were included in the study. Demographic data taken into account included age, body mass index (BMI), provenance environment, anthropometric data: Abdominal circumference and the complete set of paraclinical data from which we extracted these specific liver tests: Aspartate aminotransferase (AST), alanine transferase (ALT), direct bilirubin (BD), serum albumin and gamma-glutamyl transferase (GGT). The present study included 157 patients divided into two groups, distributed as follows: Group A: 66 obese pregnant women (BMI >25 kg/m2) and group B: 91 patients with normal weight (BMI <25 kg/m2). Measurement of serum ALT and AST were the most useful tests for routine diagnosis of liver disease. The effects of pregnancy on serum levels of ALT and AST are controversial. In some studies, there was a slight increase in ALT and AST during the second and third trimesters, a fact confirmed by our study, albeit the result was not statistically significant Most published studies claim that serum ALT and AST levels do not change during pregnancy. In conclusion, obesity during pregnancy does not drastically influence liver function. However, patients with greater abdominal circumference are prone to developing minor hepatic cytolysis syndrome during the gestation period. The liver functional tests described in the aforementioned groups agree with the results provided by the specialized studies.

Teodorescu|Cristina Oana Daciana|COD|
Șandru|Florica|F|
Charkaoui|Adham|A|
Teodorescu|Andrei|A|
Popa|Amorin Remus|AR|
Miron|Andreea-Iuliana|AI|

liver functional tests
obesity
pregnancy
body mass index
abdominal circumference


Functional anatomy of the equine temporomandibular joint: Collagen fiber texture of the articular surfaces.

Abstract: In the last decade, the equine masticatory apparatus has received much attention. Numerous studies have emphasized the importance of the temporomandibular joint (TMJ) in the functional process of mastication. However, ultrastructural and histological data providing a basis for biomechanical and histopathological considerations are not available. The aim of the present study was to analyze the architecture of the collagen fiber apparatus in the articular surfaces of the equine TMJ to reveal typical morphological features indicating biomechanical adaptions. Therefore, the collagen fiber alignment was visualized using the split-line technique in 16 adult warmblood horses without any history of TMJ disorders. Within the central two-thirds of the articular surfaces of the articular tubercle, the articular disc and the mandibular head, split-lines ran in a correspondent rostrocaudal direction. In the lateral and medial aspects of these articular surfaces, the split-line pattern varied, displaying curved arrangements in the articular disc and punctual split-lines in the bony components. Mediolateral orientated split-lines were found in the rostral and caudal border of the articular disc and in the mandibular fossa. The complex movements during the equine chewing cycle are likely assigned to different areas of the TMJ. The split-line pattern of the equine TMJ is indicative of a relative movement of the joint components in a preferential rostrocaudal direction which is consigned to the central aspects of the TMJ. The lateral and medial aspects of the articular surfaces provide split-line patterns that indicate movements particularly around a dorsoventral axis.

Adams|K|K| Schulz-Kornas|E|E| Arzi|B|B| Failing|K|K| Vogelsberg|J|J| Staszyk|C|C|

Anatomy
Temporomandibular joint
Collagen fibers
Split-lines
Horse


Physical activity during COVID-19 induced lockdown: recommendations.

Abstract: Measures aiming at containing the Coronavirus disease 2019 (COVID-19) include isolation, social distancing, and quarantine. Quarantine and other lockdown instruments show promise in reducing the number of COVID-19 infections and deaths. It is reasonable to assume that lockdown leads to reduced levels of physical activity in the general population. Potential detrimental health effects of lockdown, such as psychological distress and physical inactivity induced maladaptations must be addressed. The current review summarizes harmful effects of limited physical activity on mental and physical health due to social distancing and quarantine and highlights the effects of simple physical activity regimes counteracting these detrimental effects, with a special emphasis on acute effects.

Füzéki|Eszter|E|0000-0002-5466-7412
Groneberg|David A|DA|
Banzer|Winfried|W|


In vivo nanoparticle assessment of pathological endothelium predicts the development of inflow stenosis in murine arteriovenous fistula.

Abstract:
OBJECTIVE
In vivo assessment of pathological endothelium within arteriovenous fistula (AVF) could provide new insights into inflow stenosis, a common cause of AVF primary failure in end-stage renal disease patients. Here we developed nanoparticle-based imaging strategies to assess pathological endothelium in vivo and elucidate its relationship to neointimal hyperplasia formation in AVF.

APPROACH AND RESULTS
Jugular-carotid AVFs were created in C57BL/6 mice (n=38). Pathological endothelium in the AVF was visualized and quantified in vivo using dextranated magnetofluorescent nanoparticles (CLIO-VT680 [cross-linked iron oxide-VivoTag680]). At day 14, CLIO-VT680 was deposited in AVF, but only minimally in sham-operated arteries. Transmission electron microscopy revealed that CLIO-VT680 resided within endothelial cells and in the intimal extracellular space. Endothelial cells of AVF, but not control arteries, expressed vascular cell adhesion molecule-1 and showed augmented endothelial permeability near the anastomosis. Intravital microscopy demonstrated that CLIO-VT680 deposited most intensely near the AVF anastomosis (P<0.0001). The day 14 intravital microscopy CLIO-VT680 signal predicted the subsequent site and magnitude of AVF neointimal hyperplasia at day 42 (r=0.58, P<0.05). CLIO-VT680 deposition in AVF was further visualized by ex vivo MRI.

CONCLUSIONS
AVF develop a pathological endothelial response that can be assessed in vivo via nanoparticle-enhanced imaging. AVF endothelium is activated and exhibits augmented permeability, offering a targeting mechanism for nanoparticle deposition and retention in pathological endothelium. The in vivo AVF nanoparticle signal identified and predicted subsequent inflow neointimal hyperplasia. This approach could be used to test therapeutic interventions aiming to restore endothelial health and to decrease early AVF failure caused by inflow stenosis.

Cui|Jie|J|
Kessinger|Chase W|CW|
McCarthy|Jason R|JR|
Sosnovik|David E|DE|
Libby|Peter|P|
Thadhani|Ravi I|RI|
Jaffer|Farouc A|FA|

D019010:Vascular Cell Adhesion Molecule-1

endothelium
stenosis
arteriovenous fistula
imaging


The putative transcription factor CaRtg3 is involved in tolerance to cations and antifungal drugs as well as serum-induced filamentation in Candida albicans.

Abstract: The activated retrograde (RTG) pathway controls transcription of target genes through a heterodimer of transcription factors, Rtg1 and Rtg3, in Saccharomyces cerevisiae. Here, we have identified the sole homologous gene CaRTG3 that encodes a protein of 520 amino acids with characteristics of the basic helix-loop-helix/leucine zipper (bHLH/Zip) family in Candida albicans. Deletion of CaRTG3 results in C. albicans cells being sensitive to high concentrations of calcium and lithium cations as well as sodium dodecyl sulfate and activates the calcium/calcineurin signaling pathway in C. albicans cells. CaRTG3 is also involved in the tolerance of C. albicans cells to the antifungal drugs azoles and terbinafine, but not to the antifungal drugs casponfungin and amphotericin B as well as the cell-wall-damaging reagents Calcoflour White and Congo red. In contrast to ScRtg3, CaRtg3 is not involved in the osmolar response and is constitutively localized in the nucleus. However, deletion of CaRTG3 results in a delay in serum-induced filamentation of C. albicans cells. Therefore, CaRtg3 plays a role in tolerance to cations and antifungal drugs as well as serum-induced filamentation in C. albicans.

D015966:Gene Expression Regulation, Fungal

antifungal drugs
filamentation
Rtg3
calcium
lithium


Recent Progress in Interconnection Layer for Hybrid Photovoltaic Tandems.

Abstract: Hybrid tandem solar cells offer the benefits of low cost and full solar spectrum utilization. Among the hybrid tandem structures explored to date, the most popular ones have four (simple stacking design) or two (terminal/tunneling layer addition design) terminal electrodes. Although the latter design is more cost-effective than the former, its widespread application is hindered by the difficulty of preparing an interface between two solar cell materials. The oldest approach to the in-series bonding of two or more bandgap solar cells relies on the introduction of a tunneling layer in multijunction III-V solar cells, but it has some limitations, e.g., the related materials/technologies are applicable only to III-V and certain other solar cells. Thus, alternative methods of realizing junction contacts based on the use of novel materials are highly sought after. Here, the strategies used to realize high-performance tandem cells are described, focusing on interface control in terms of bonding two or more solar cells for tandem approaches. The presented information is expected to aid the establishment of ideal methods of connecting two or more solar cells to obtain the highest performance for different solar cell choices with minimized energy loss through the interface.

hybrid photovoltaic tandems
solar cells
intermediate layers
perovskites
silicon


Time Release of Encapsulated Additives for Enhanced Performance of Lithium-Ion Batteries.

Abstract: Time release of encapsulated vinylene carbonate (VC) from microcapsules in Li-ion batteries is demonstrated to enhance the rate performance without sacrificing capacity retention. VC-filled microcapsules are successfully prepared by the solvent exchange method that allows VC to diffuse through the microcapsule shell wall at an elevated temperature. The concentration of VC added directly to the electrolyte in a pouch cell (2 wt %) significantly decreases after the first cycle at C/10-rate. In pouch cells that contain 5 wt % VC-filled microcapsules, the concentration of VC increases from 0 to 3 wt % over the first cycle because of the diffusion of microencapsulated VC in the electrolyte. Electrochemical impedance spectroscopy, rate capability, and long-term cycling tests are conducted for pouch cells with VC additives (0, 2, and 5 wt %) and VC microcapsules (5 wt %). Pouch cells with both 5 wt % VC additive and microencapsulated VC show improved capacity retention over 400 cycles at 1 C-rate compared to the cells without VC additive. When VC is added directly, the high initial concentration leads to increased interfacial resistance and decreased rate capability. By contrast, time release of microencapsulated VC by diffusion through microcapsules increases the discharge capacity 2.5 times at 5 C-rate compared to the direct VC addition to the electrolyte.

time release
lithium-ion batteries
vinylene carbonate
microcapsules
battery additives


Pretreatment biomarkers predicting PTSD psychotherapy outcomes: A systematic review.

Abstract: Although our understanding of the relationship between posttraumatic stress disorder (PTSD), brain structure and function, neural networks, stress-related systems, and genetics is growing, there is considerably less attention given to which biological markers predict evidence-based PTSD psychotherapy outcomes. Our systematic PRISMA-informed review of 20 studies examined biomarkers as predictors of evidence-based PTSD psychotherapy outcomes. Results provide preliminary evidence that specific structural and functional neural systems (involved in information processing), glucocorticoid sensitivity and metabolism (part of the hypothalamic-pituitary-adrenal axis and the response to stress), heart rate (involved with fear habituation), gene methylation, and certain genotypes (associated with serotonin and glucocorticoids) predicted positive response to PTSD treatment. These pre-treatment biomarkers are associated with processes integral to PTSD treatment, such as those affecting fear learning and extinction, cognitive restructuring, information processing, emotional processing, and interoceptive monitoring. Identifying pre-treatment biomarkers that predict treatment response may offer insight into the mechanisms of psychological treatment, provide a foundation for improving the pharmaceutical augmentation of treatment, and inform treatment matching.

Colvonen|Peter J|PJ|
Glassman|Lisa H|LH|
Crocker|Laura D|LD|
Buttner|Melissa M|MM|
Orff|Henry|H|
Schiehser|Dawn M|DM|
Norman|Sonya B|SB|
Afari|Niloofar|N|

Biomarkers
Review
Glucocorticoids
Heart rate
Genes
Neuroimaging
PTSD treatment outcomes


Regulating the local availability of tobacco retailing in Madrid, Spain: a GIS study to evaluate compliance.

Abstract:
BACKGROUND
In Spain, tobacco sales are limited to tobacco-exclusive stores and associated vending machines. A minimum of 150 m between stores is required, unless they exceed a legal sales threshold. Minimum distances to schools are recommended but not defined. We evaluated compliance with these regulations in Madrid, Spain.

METHODS
Information about tobacco-exclusive stores and their sales volume was obtained in 2014. We used geographic information system to identify stores closer than 150 m between them and examine whether they exceeded the sales threshold. We estimated distances between stores and schools, considering different distance intervals (<150 m, 150-300 m and >300 m) and calculations (crow flies and street network). We assessed the association of area-level demographic and socioeconomic characteristics with the distribution of tobacco stores.

RESULTS
5.3% (34/638) of tobacco stores were within 150 m of each other. Among those, 76% (26/34) did not meet the regulation sales threshold. These stores were in areas with lower proportion of young population (<15 years) and higher proportion of people with university-level education. 75% (476/638) of stores were situated closer than 300 m to schools. No differences were identified in sociodemographic and economic characteristics by the store distance to schools.

CONCLUSION
Most tobacco stores are compliant with the regulations in Spain. However, these regulations are insufficient to reduce tobacco availability. More restrictive regulations are needed to limit the geographic distribution of tobacco retailers, and health criteria should also be considered in the current legislation. The evaluation of the Spanish regulatory model may provide useful insights for other jurisdictions looking to decrease the tobacco retail availability.

Valiente|Roberto|R| Sureda|Xisca|X| Bilal|Usama|U|0000-0002-9868-7773 Navas-Acien|Ana|A| Pearce|Jamie|J| Franco|Manuel|M| Escobar|Francisco|F|

schools
tobacco availability
proximity analysis
tobacco retail regulations
tobacco stores distribution


Silicosis and lung cancer: current perspectives.

Abstract: "Silica" refers to crystalline particles formed by the combination of silicon with oxygen. Inhalation of silica particles promotes the development of pulmonary fibrosis that over prolonged periods increases the risk of lung cancer. The International Agency for Research on Cancer (IARC) classified crystalline silica as a human carcinogen in 1997. This categorization was questioned due to 1) the absence of dose-response findings, 2) the presence of confounding variables that complicated interpretation of the data and 3) potential selection bias for compensated silicosis. Yet, recent epidemiologic studies strongly support the conclusion that silica exposure increases the risk of lung cancer in humans independent of confounding factors including cigarette smoke. Based on this evidence, the US Occupational Safety and Health Administration (OSHA) lowered the occupational exposure limit for crystalline silica from 0.1 to 0.05 mg/m3 in 2013. Further supporting the human epidemiologic data, murine models show that chronic silicosis is associated with an increased risk of lung cancer. In animals, the initial inflammation induced by silica exposure is followed by the development of an immunosuppressive microenvironment that supports the growth of lung tumors. This work will review our current knowledge of silica-associated lung cancers, highlighting how recent mechanistic insights support the use of cutting-edge approaches to diagnose and treat silica-related lung cancer.

Sato|Takashi|T|
Shimosato|Takeshi|T|
Klinman|Dennis M|DM|

silicosis
lung cancer
fibrosis
inflammation
occupational lung disease


A Fast and Accessible Method for the Isolation of RNA, DNA, and Protein To Facilitate the Detection of SARS-CoV-2.

Abstract: Management of the coronavirus disease 2019 (COVID-19) pandemic requires widespread testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A main limitation for widespread SARS-CoV-2 testing is the global shortage of essential supplies, among them RNA extraction kits. The need for commercial RNA extraction kits places a bottleneck on tests that detect SARS-CoV-2 genetic material, including PCR-based reference tests. Here, we propose an alternative method we call PEARL (precipitation-enhanced analyte retrieval) that addresses this limitation. PEARL uses a lysis solution that disrupts cell membranes and viral envelopes while simultaneously providing conditions suitable for alcohol-based precipitation of RNA, DNA, and proteins. PEARL is a fast, low-cost, and simple method that uses common laboratory reagents and offers performance comparable to that of commercial RNA extraction kits. PEARL offers an alternative method to isolate host and pathogen nucleic acids and proteins to streamline the detection of DNA and RNA viruses, including SARS-CoV-2.

SARS-CoV-2
DNA and protein
field deployable
rapid isolation of RNA
virus detection


Gender Differences in the Reporting of Vocal Fatigue in Teachers as Quantified by the Vocal Fatigue Index.

Abstract:
OBJECTIVES
Occupational voice users report higher instances of vocal health problems. Women, who are more likely than men to report voice problems, are the largest members of some occupational voice users, such as teachers. While a common complaint among this population is vocal fatigue, it has been difficult to quantify. Therefore, the goal of this study is to quantify vocal fatigue generally in school teachers and investigate any related gender differences.

METHODS
Six hundred forty (518 female, 122 male) teachers were surveyed using an online questionnaire consisting in part of the Vocal Fatigue Index (VFI), an index specifically designed to quantify vocal fatigue.

RESULTS
Compared to vocally healthy adults, the teachers surveyed were 3 times as likely to report vocal tiredness or vocal avoidance and over 3 times as likely to report physical voice discomfort. Additionally, female teachers were more likely to have scores approaching those with dysphonia.

CONCLUSIONS
The VFI quantified elevated levels of vocal fatigue in teachers, with a significant prevalence of symptoms reported among females compared to males. Further, because the VFI indicated elevated complaints (between normal and dysphonic) in a population likely to be elevated, the VFI might be used to identify early indications of voice problems and/or track recovery.

vocal fatigue
occupational voice use
voice disorders
voice recovery


A novel covalent approach to bio-conjugate silver coated single walled carbon nanotubes with antimicrobial peptide.

Abstract:
BACKGROUND
Due to increasing antibiotic resistance, the use of silver coated single walled carbon nanotubes (SWCNTs-Ag) and antimicrobial peptides (APs) is becoming popular due to their antimicrobial properties against a wide range of pathogens. However, stability against various conditions and toxicity in human cells are some of the major drawbacks of APs and SWCNTs-Ag, respectively. Therefore, we hypothesized that APs-functionalized SWCNTs-Ag could act synergistically. Various covalent functionalization protocols described previously involve harsh treatment of carbon nanotubes for carboxylation (first step in covalent functionalization) and the non-covalently functionalized SWCNTs are not satisfactory.

METHODS
The present study is the first report wherein SWCNTs-Ag were first carboxylated using Tri sodium citrate (TSC) at 37 °C and then subsequently functionalized covalently with an effective antimicrobial peptide from Therapeutic Inc., TP359 (FSWCNTs-Ag). SWCNTs-Ag were also non covalently functionalized with TP359 by simple mixing (SWCNTs-Ag-M) and both, the FSWCNTs-Ag (covalent) and SWCNTs-Ag-M (non-covalent), were characterized by Fourier transform infrared spectroscopy (FT-IR), Ultraviolet visualization (UV-VIS) and transmission electron microscopy (TEM). Further the antibacterial activity of both and TP359 were investigated against two gram positive (Staphylococcus aureus and Streptococcus pyogenes) and two gram negative (Salmonella enterica serovar Typhimurium and Escherichia coli) pathogens and the cellular toxicity of TP359 and FSWCNTs-Ag was compared with plain SWCNTs-Ag using murine macrophages and lung carcinoma cells.

RESULTS
FT-IR analysis revealed that treatment with TSC successfully resulted in carboxylation of SWCNTs-Ag and the peptide was indeed attached to the SWCNTs-Ag evidenced by TEM images. More importantly, the present study results further showed that the minimum inhibitory concentration (MIC) of FSWCNTs-Ag were much lower (~7.8-3.9 µg/ml with IC50: ~4-5 µg/ml) compared to SWCNTs-Ag-M and plain SWCNTs-Ag (both 62.6 µg/ml, IC50: ~31-35 µg/ml), suggesting that the covalent conjugation of TP359 with SWCNTs-Ag was very effective on their counterparts. Additionally, FSWCNTs-Ag are non-toxic to the eukaryotic cells at their MIC concentrations (5-2.5 µg/ml) compared to SWCNTs-Ag (62.5 µg/ml).

CONCLUSION
In conclusion, we demonstrated that covalent functionalization of SWCNTs-Ag and TP359 exhibited an additive antibacterial activity. This study described a novel approach to prepare SWCNT-Ag bio-conjugates without loss of antimicrobial activity and reduced toxicity, and this strategy will aid in the development of novel and biologically important nanomaterials.

Chaudhari|Atul A|AA|
Ashmore|D'andrea|D|
Nath|Subrata Deb|SD|
Kate|Kunal|K|
Dennis|Vida|V|
Singh|Shree R|SR|
Owen|Don R|DR|
Palazzo|Chris|C|
Arnold|Robert D|RD|
Miller|Michael E|ME|
Pillai|Shreekumar R|SR|

Bio-conjugation
Carbon nanotubes
Antimicrobial
Peptide
Bacteria
Cytotoxicity


Virtual water and water self-sufficiency in agricultural and livestock products in Brazil.

Abstract: Virtual water trade is often considered a solution for restricted water availability in many regions of the world. Brazil is the world leader in the production and export of various agricultural and livestock products. The country is either a strong net importer or a strong net exporter of these products. The objective of this study is to determine the volume of virtual water contained in agricultural and livestock products imported/exported by Brazil from 1997 to 2012, and to define the water self-sufficiency index of agricultural and livestock products in Brazil. The indexes of water scarcity (WSI), water dependency (WDI) and water self-sufficiency (WSSI) were calculated for each Brazilian state. These indexes and the virtual water balance were calculated following the methodology developed by Chapagain and Hoekstra (2008) and Hoekstra and Hung (2005). The total water exports and imports embedded in agricultural and livestock products were 5.28 × 1010 and 1.22 × 1010 Gm3 yr-1, respectively, which results in positive virtual water balance of 4.05 × 1010 Gm3 yr-1. Brazil is either a strong net importer or a strong net exporter of agricultural and livestock products among the Mercosur countries. Brazil has a positive virtual water balance of 1.85 × 1010 Gm3 yr-1. The indexes used in this study reveal that Brazil is self-sufficient in food production, except for a few products such as wheat and rice. Horticultural products (tomato, onion, potato, cassava and garlic) make up a unique product group with negative virtual water balance in Brazil.

da Silva|Vicente de Paulo R|VPR|
de Oliveira|Sonaly D|SD|
Braga|Célia C|CC|
Brito|José Ivaldo B|JIB|
de Sousa|Francisco de Assis S|FAS|
de Holanda|Romildo M|RM|
Campos|João Hugo B C|JHBC|
de Souza|Enio P|EP|
Braga|Armando César R|ACR|
Rodrigues Almeida|Rafaela S|RS|
de Araújo|Lincoln E|LE|

Water trade
Virtual water balance
Exports and imports
Water dependency index


Avascular necrosis in systemic sclerosis patients: a case-based review of demographics, presentation, and management.

Abstract: Avascular necrosis (AVN) is a pathologic process involving death of bony tissue resulting from loss of blood supply from various causes. Various traumatic and nontraumatic causes of AVN are known, including systemic autoimmune diseases. AVN has been well described in patients with autoimmune diseases such as systemic lupus erythematosus, but in systemic sclerosis (SSc) patients, there have been limited case reports and case series. There have only been three case reports of AVN in multiple anatomic sites (multifocal AVN) reported in SSc patients in the literature. We present a case of multifocal AVN in an SSc patient and a review of literature on the previously reported cases of SSc-related AVN in terms of demographics, clinical presentation, and management. To our knowledge, this is the only literature review of reported AVN cases in SSc patients.

Avascular necrosis
Systemic sclerosis
Autoimmune diseases
Osteonecrosis
Scleroderma


Patient selection for thoracic radiotherapy in extensive-stage small-cell lung cancer.

Abstract: Treatment of extensive-stage small-cell lung cancer remains a challenge with poor local control and overall survival. Chemotherapy is the mainstay of treatment, consisting of a combination of a platinum agent plus etoposide. The role of consolidative chest radiotherapy in extensive-stage small-cell lung cancer remains controversial. Two randomized clinical trials have been published demonstrating improved intrathoracic disease control with a small survival benefit, though interpretation and application of these results to clinical practice has been debated. These two trials examined different radiotherapy techniques and doses, with a third trial treating consolidative chest and oligometastatic disease having closed prematurely due to an interim analysis demonstrating treatment futility plus increased toxicity. Patients with residual intrathoracic disease after chemotherapy appear to benefit the most from consolidative chest radiotherapy, offering a potential tool to help select appropriate patients.

Corkum|Mark T|MT|
Rodrigues|George B|GB|

patient selection
extensive-stage
small-cell lung cancers
consolidative radiotherapy


A facile strategy to fabricate a pH-responsive mesoporous silica nanoparticle end-capped with amphiphilic peptides by self-assembly.

Abstract: A facile strategy with no modification processes was demonstrated to fabricate a pH-responsive end-capped mesoporous silica nanoparticle (MSN)-based drug delivery system (DDS). The simple but smart nanovalve systems were constructed by the self-assembly behavior of unbonded peptide-based amphiphile (P45) in the presence of Doxorubicin hydrochloride (Dox). A series of characterizations confirmed that the DDSs had been successfully fabricated. Dox molecules were entrapped by nanovalves in the pores of MSNs, and an in vitro release experiment demonstrated that the P45/Dox@MSNs exhibited "zero premature release" in the physical environment. However, an accelerated release was triggered by an acidic atmosphere in cellular cytosol. Moreover, detailed investigations confirmed that the enhanced cellular uptake of P45/Dox@MSNs due to the RGD motif of the nanovalves, exhibiting an obvious toxicity to cancer cells. Therefore, the DDSs constructed here can serve as a promising platform to realize targeted drug delivery and controlled drug release by using diversified bioactive native amphiphilic peptide.

Zhao|Fengfeng|F| Zhang|Chen|C| Zhao|Chenggui|C| Gao|Wei|W| Fan|Xiaobo|X| Wu|Guoqiu|G|

pH-responsive
Mesoporous silica nanoparticles
Targeted drug delivery
Native amphiphilic peptide
cOntrol release


Ablation of plasma membrane Ca(2+)-ATPase isoform 4 prevents development of hypertrophy in a model of hypertrophic cardiomyopathy.

Abstract: The mechanisms linking the expression of sarcomeric mutant proteins to the development of pathological hypertrophy in hypertrophic cardiomyopathy (HCM) remain poorly understood. We investigated the role of the plasma membrane Ca(2+)-ATPase PMCA4 in the HCM phenotype using a transgenic model that expresses mutant (Glu180Gly) α-tropomyosin (Tm180) in heart. Immunoblot analysis revealed that cardiac PMCA4 expression was upregulated early in Tm180 disease pathogenesis. This was accompanied by an increase in levels of the L-type Ca(2+)-channel, which is implicated in pathological hypertrophy. When Tm180 mice were crossed with a PMCA4-null line, loss of PMCA4 caused the abrogation of hypertrophy in Tm180/PMCA4-null double mutant mice. RT-PCR analysis of Tm180/PMCA4-null hearts revealed blunting of the fetal program and reversion of pro-fibrotic Col1a1 and Col3a1 gene expression to wild-type levels. This was accompanied by evidence of reduced L-type Ca(2+)-channel expression, and diminished calcineurin activity. Expression of the metabolic substrate transporters glucose transporter 4 and carnitine palmitoyltransferase 1b was preserved and Tm180-related changes in mRNA levels of various contractile stress-related proteins including the cardiac ankyrin protein CARP and the N2B isoform of titin were reversed in Tm180/PMCA4-null hearts. cGMP levels were increased and phosphorylation of vasodilator-stimulated phosphoprotein was elevated in Tm180/PMCA4-null hearts. These changes were associated with a sharp reduction in left ventricular end-diastolic pressure in Tm180/PMCA4-null hearts, which occurred despite persistence of Tm180-related impairment of relaxation dynamics. These results reveal a novel and specific role for PMCA4 in the Tm180 hypertrophic phenotype, with the "protective" effects of PMCA4 deficiency encompassing multiple determinants of HCM-related hypertrophy.

Prasad|Vikram|V|
Lorenz|John N|JN|
Lasko|Valerie M|VM|
Nieman|Michelle L|ML|
Jiang|Min|M|
Gao|Xu|X|
Rubinstein|Jack|J|
Wieczorek|David F|DF|
Shull|Gary E|GE|

D053499:Plasma Membrane Calcium-Transporting ATPases

Hypertrophic cardiomyopathy
Pathological hypertrophy
PMCA4
Diastolic dysfunction
Diastolic properties
Ventricular stiffness


Humic substances cause fluorescence inhibition in real-time polymerase chain reaction.

Abstract: Real-time polymerase chain reaction (qPCR) is the cornerstone of DNA analysis, enabling detection and quantification of minute nucleic acid amounts. However, PCR-based analysis is limited, in part, by the presence of inhibitors in the samples. PCR inhibition has been viewed solely as failure to efficiently generate amplicons, that is, amplification inhibition. Humic substances (HS) are well-known inhibitors of PCR amplification. Here we show that HS from environmental samples, specifically humic acid (HA), are very potent detection inhibitors, that is, quench the fluorescence signal of double-stranded DNA (dsDNA) binding dyes. HA quenched the fluorescence of the commonly used qPCR dyes EvaGreen, ResoLight, SYBR Green I, and SYTO 82, generating lowered amplification plots, although amplicon production was unaffected. For EvaGreen, 500 ng of HA quenched nearly all fluorescence, whereas 1000 ng of HA completely inhibited amplification when applying Immolase DNA polymerase with bovine serum albumin (BSA). Fluorescence spectroscopy measurements showed that HA quenching was either static or collisional and indicated that HA bound directly to the dye. Fulvic acid did not act as a qPCR detection inhibitor but inhibited amplification similarly to HA. Hydrolysis probe fluorescence was not quenched by HA. Detection inhibition is an overlooked phenomenon that needs to be considered to allow for development of optimal qPCR assays.

Sidstedt|Maja|M| Jansson|Linda|L| Nilsson|Elin|E| Noppa|Laila|L| Forsman|Mats|M| Rådström|Peter|P| Hedman|Johannes|J|

D060888:Real-Time Polymerase Chain Reaction

qPCR
PCR inhibition
Humic acid
Fulvic acid
Fluorescence quenching
Soil


Incidence and prevalence of lupus in Buenos Aires, Argentina: a 11-year health management organisation-based study.

Abstract:
OBJECTIVES
Studies regarding the epidemiology of systemic lupus erythematosus (SLE) are lacking in Argentina. Our purpose was to estimate the incidence and prevalence of SLE in a university hospital-based health management organisation in Buenos Aires (HIMCP).

METHODS
For incidence calculation, the population at risk included all adult members of the HIMCP, with continuous affiliation for at least 1 year from January 1998 to January 2009. Each person was followed until he/she voluntarily left the HIMCP, death or finalisation of the study. Multiple methods for case finding were used to ensure complete ascertainment: (a) patients with problem SLE, undifferentiated autoimmune disease or mixed connective tissue disease in the Computer-based Patient Record System, (b) patients with positive antinuclear antibody test, anti-Sm antibodies and/or anti-dsDNA antibodies in the laboratory database and (c) patients who consumed hydroxichloroquine, chloroquine, azathioprine, cyclophosphamide, mycophenolate, cyclosporine or rituximab, from the administrative HIMCP drugs database. Medical records of all patients found were reviewed, and only patients fulfilling ACR criteria for SLE were included. Global and gender incidence rate (IR) was calculated. Prevalence was estimated on 1 January 2009, and the denominator population was the number of active members >18 years at that date (n=127 959).

RESULTS
In the study period, 68 patients developed SLE. The observed IR (per 100 000 person-years, (CI 95%)) was 6.3 (4.9 to 7.7) for total population; 8.9 (CI 6.6 to 11.2) for women and 2.6 (1.2 to 3.9) for men. On 1 January 2009, 75 prevalent cases were identified. Prevalence rates (cases per 100 000 habitants, (CI 95%)) were 58.6 (46.1 to 73.5) for total population; 83.2 (63.9 to 106.4) for women and 23 (CI 11.9 to 40.1) for men.

CONCLUSIONS
SLE incidence and prevalence rates in Argentina are in agreement with those of other studies from different parts of the world.

Scolnik|M|M|
Marin|J|J|
Valeiras|S M|SM|
Marchese|M F|MF|
Talani|A S|AS|
Avellaneda|N L|NL|
Etchepare|A|A|
Etchepare|P|P|
Plou|M S|MS|
Soriano|E R|ER|

Epidemiology
Systemic Lupus Erythematosus
Autoimmune Diseases


Interrogation of EGFR Targeted Uptake of TiO2 Nanoconjugates by X-ray Fluorescence Microscopy.

Abstract: We are developing TiO2 nanoconjugates that can be used as therapeutic and diagnostic agents. Nanoscale TiO2 can be surface conjugated with various molecules and has the unique ability to induce the production of reactive oxygen species after radiation activation. One way to improve the potential clinical usefulness of TiO2 nanoparticles is to control their delivery to malignant cells by targeting them to cancer cell specific antigens. Epidermal Growth Factor Receptor is one potential target that is enriched in epithelial cancers and is rapidly internalized after ligand binding. Hence, we have synthesized TiO2 nanoparticles and functionalized them with a short EGFR binding peptide to create EGFR-targeted NCs. X-ray Fluorescence Microscopy was used to image nanoconjugates within EGFR positive HeLa cells. Further labeling of fixed cells with antibodies against EGFR and Protein A nanogold showed that TiO2 nanoconjugates can colocalize with receptors at the cell's plasma membrane. Interestingly, with increased incubation times, EGFR targeted nanoconjugates could also be found colocalized with EGFR within the cell nucleus. This suggests that EGFR-targeted nanoconjugates can bind the receptor at the cell membrane, which leads to the internalization of NC-receptor complexes and the subsequent transport of nanoconjugates into the nucleus.

Yuan|Ye|Y| Paunesku|Tatjana|T| Arora|Hans|H| Ward|Jesse|J| Vogt|Stefan|S| Woloschak|Gayle|G|


Comparing a Yoga Class with a Resistance Exercise Class: Effects on Body Satisfaction and Social Physique Anxiety in University Women.

Abstract:
PURPOSE
The current study compared a single yoga group exercise class and a resistance group exercise class for their effects on state body satisfaction and social physique anxiety in women.

METHODS
A pretest-posttest design was used. Participants (N = 46) completed both a resistance exercise class and yoga class in a counterbalanced order. Measures of body satisfaction and social physique anxiety were completed immediately before and after each class.

RESULTS
A 2 (time) × 2 (class type) repeatedmeasures multiple analysis of variance showed a significant overall Time × Class Type interaction (F2,44 = 5.69, P < .01, η p2 = .21). There was a significant increase in body satisfaction after the yoga class. After both classes, there was a significant decrease in social physique anxiety, but the magnitude of the change was larger after the yoga class than after the resistance class.

CONCLUSIONS
Both types of exercise class were associated with improvements in body image, but there were greater improvements after the yoga class. This study provided evidence of the positive effects of yoga for reducing state social physique anxiety and increasing state body satisfaction, adding to correlational evidence suggesting that yoga is particularly beneficial for improving body image-related outcomes in women.

Gammage|Kimberley L|KL|
Drouin|Breanne|B|
Lamarche|Larkin|L|

group exercise
body image
acute exercise
physical activity


The cancellation of mass gatherings (MGs)? Decision making in the time of COVID-19.

Abstract: Our recommendation, as experts who have monitored health hazards at the Hajj for over 15 years, especially if the situation with COVID-19 continues to escalate globally is that Hajj 2020 will be at risk of being suspended and a means for Muslims to fulfill their rights in the future either personally or even by proxy need to be announced. The same holds true for the Summer 2020 Olympics in Japan and for many other MGs and large gatherings. Decisions in the time of COVID-19 will be closely followed and will be a blueprint for other mass gatherings.

Mass gathering
COVID-19
Hajj
Olympics
SARS-CoV-2
Umrah


Aortitis Presenting as Fever of Unknown Origin.

Abstract: Patients with aortitis often present with nonspecific constitutional symptoms. Due to the fact that aortitis is associated with inflammatory or infectious courses, patients may manifest fever or fever of unknown origin. Such clinical characteristics of aortitis are unavoidably brought about diagnostic dilemmas and might lead to a series of unnecessary work-ups and maltreatment. Therefore, it is important for the clinical physicians and surgeons to understand aortitis presenting with fever of unknown origin to avoid delayed diagnosis and treatment. In this article, clinical and pathological features of aortitis (giant cell arteritis, Takayasu arteritis and infective aortitis, etc.) with fever of unknown origin are described and the differential diagnosis and management policy are discussed.

aortitis
fever of unknown origin
giant cell arteritis
Takayasu arteritis
cardiovascular syphilis


Microscopic Three-Dimensional Measurement Based on Telecentric Stereo and Speckle Projection Methods.

Abstract: Three-dimensional (3D) measurement of microstructures has become increasingly important, and many microscopic measurement methods have been developed. For the dimension in several millimeters together with the accuracy at sub-pixel or sub-micron level, there is almost no effective measurement method now. Here we present a method combining the microscopic stereo measurement with the digital speckle projection. A microscopy experimental setup mainly composed of two telecentric cameras and an industrial projection module is established and a telecentric binocular stereo reconstruction procedure is carried out. The measurement accuracy has firstly been verified by performing 3D measurements of grid arrays at different locations and cylinder arrays with different height differences. Then two Mitutoyo step masters have been used for further verification. The experimental results show that the proposed method can obtain 3D information of the microstructure with a sub-pixel and even sub-micron measuring accuracy in millimeter scale.

Chen|Kepeng|K| Shi|Tielin|T| Liu|Qiang|Q| Tang|Zirong|Z| Liao|Guanglan|G|

speckle projection
microscopic measurement
telecentric cameras
stereo vision


A New Method for Cartilage Evaluation in Femoroacetabular Impingement Using Quantitative T2 Magnetic Resonance Imaging: Preliminary Validation against Arthroscopic Findings.

Abstract:
OBJECTIVE
The outcome of arthroscopic treatment for femoroacetabular impingement (FAI) depends on the preoperative status of the hip cartilage. Quantitative T2 can detect early biochemical cartilage changes, but its routine implementation is challenging. Furthermore, intrinsic T2 variability between patients makes it difficult to define a threshold to identify cartilage lesions. To address this, we propose a normalized T2-index as a new method to evaluate cartilage in FAI.

DESIGN
We retrospectively analyzed magnetic resonance imaging (MRI) data of 18 FAI patients with arthroscopically confirmed cartilage defects. Cartilage T2 maps were reconstructed from multi-spin-echo 3-T data using the echo-modulation-curve (EMC) model-based technique. The central femoral cartilage, assumed healthy in early-stage FAI, was used as the normalization reference to define a T2-index. We investigated the ability of the T2-index to detect surgically confirmed cartilage lesions.

RESULTS
The average T2-index was 1.14 ± 0.1 and 1.13 ± 0.1 for 2 separated segmentations. Using T2-index >1 as the threshold for damaged cartilage, accuracy was 88% and 100% for the 2 segmentations. We found moderate intraobserver repeatability, although separate segmentations yielded comparable accuracy. Damaged cartilage could not be identified using nonnormalized average T2 values.

CONCLUSIONS
This preliminary study confirms the importance of normalizing T2 values to account for interpatient variability and suggests that the T2-index is a promising biomarker for the detection of cartilage lesions in FAI. Future work is needed to confirm that combining T2-index with morphologic MRI and other quantitative biomarkers could improve cartilage assessment in FAI.


An Inter-Supplementary Biohybrid System Based on Natural Killer Cells for the Combinational Immunotherapy and Virotherapy of Cancer.

Abstract: Oncolytic adenoviruses (Ads) have gained great attention in cancer therapy because they cause direct cytolytic infection and indirectly induce antitumor immunity. However, their efficacy is compromised by host antiviral immune response, poor tumor delivery, and the immunosuppressive tumor microenvironment (TME). Here, a natural killer (NK) cell-mediated Ad delivery system (Ad@NK) is generated by harnessing the merits of the two components for combinational immunotherapy and virotherapy of cancer. In this biohybrid system, NK cells with a tumor-homing tropism act as bioreactors and shelters for the loading, protection, replication, amplification, and release of Ads, thereby leading to a highly efficient systemic tumor-targeted delivery. As feedback, Ad infection offers NK cells an enhanced antitumor immunity by activating type I interferon signaling in a STAT4-granzyme B-dependent manner. Moreover, it is found that the Ad@NK system can relieve immunosuppression in the TME by promoting the maturation of dendritic cells and the polarization of macrophages to M1 phenotype. Both in vitro and in vivo data indicate the excellent antitumor and antimetastatic functions of Ad@NKs by destroying tumor cells, inducing immunogenic cell death, and immunomodulating TME. This work provides a clinical basis for improved oncolytic virotherapy in combination with NK cell therapy based on the inter-supplementary biohybrid system.

natural killer cells
tumor-targeted delivery
anticancer immunity
cell carriers
oncolytic adenovirus


Chia and oat emulsion gels as new animal fat replacers and healthy bioactive sources in fresh sausage formulation.

Abstract: This paper examines the effect of emulsion gels (EG) prepared with chia (CEG) and oats (OEG) used as animal fat replacers in reduced-fat fresh sausages (longaniza) (LRF) during chilled storage. Reduced-fat samples were reformulated with CEG and OEG, (LRF/CEG and LRF/OEG respectively). Normal (LNF/P) and reduced-fat (LRF/P) (all-pork-fat) sausages were used as controls. Nutritional composition and microbiological, technological and sensory characteristics of sausages were evaluated. The presence of an EG affected (P<0.05) the concentrations of some minerals and amino acids in sausages. CEG improved MUFA and PUFA contents. Cooking loss was lower (P<0.05) in LRF/CEG and LRF/OEG than in the controls. Of all the reduced-fat samples, Kramer shear force values (KSF) were highest (P<0.05) in the ones containing an EG. KSF generally increased (P<0.05) over storage in all samples. The microbial count was significantly affected by the use of CEG. Sensory properties were affected by the incorporation of an EG, but all sausages were judged acceptable.

Pintado|T|T|
Herrero|A M|AM|
Jiménez-Colmenero|F|F|
Pasqualin Cavalheiro|C|C|
Ruiz-Capillas|C|C|

Chia
Oat
Emulsion gel
Fresh sausage
Nutritional composition
Technological properties


Development of a web-based tool for automated processing and cataloging of a unique combinatorial drug screen.

Abstract: Facing totally resistant bacteria, traditional drug discovery efforts have proven to be of limited use in replenishing our depleted arsenal of therapeutic antibiotics. Recently, the natural anti-bacterial properties of metal ions in synergy with metal-coordinating ligands have shown potential for generating new molecule candidates with potential therapeutic downstream applications. We recently developed a novel combinatorial screening approach to identify compounds with copper-dependent anti-bacterial properties. Through a parallel screening technique, the assay distinguishes between copper-dependent and independent activities against Mycobacterium tuberculosis with hits being defined as compounds with copper-dependent activities. These activities must then be linked to a compound master list to process and analyze the data and to identify the hit molecules, a labor intensive and mistake-prone analysis. Here, we describe a software program built to automate this analysis in order to streamline our workflow significantly. We conducted a small, 1440 compound screen against M. tuberculosis and used it as an example framework to build and optimize the software. Though specifically adapted to our own needs, it can be readily expanded for any small- to medium-throughput screening effort, parallel or conventional. Further, by virtue of the underlying Linux server, it can be easily adapted for chemoinformatic analysis of screens through packages such as OpenBabel. Overall, this setup represents an easy-to-use solution for streamlining processing and analysis of biological screening data, as well as offering a scaffold for ready functionality expansion.

Combinatorial screen
Tuberculosis
Chemoinformatics
Copper
High throughput screen


The Cardioprotective Role of Flaxseed in the Prevention of Doxorubicin- and Trastuzumab-Mediated Cardiotoxicity in C57BL/6 Mice.

Abstract:
BACKGROUND
Although the combination of doxorubicin (DOX) and trastuzumab (TRZ) reduces the progression and recurrence of breast cancer, these anticancer drugs are associated with significant cardiotoxic side effects.

OBJECTIVE
We investigated whether prophylactic administration of flaxseed (FLX) and its bioactive components, α-linolenic acid (ALA) and secoisolariciresinol diglucoside (SDG), would be cardioprotective against DOX + TRZ-mediated cardiotoxicity in a chronic in vivo female murine model.

METHODS
Wild-type C57BL/6 female mice (10-12 wk old) received daily prophylactic treatment with one of the following diets: 1) regular control (RC) semi-purified diet; 2) 10% FLX diet; 3) 4.4% ALA diet; or 4) 0.44% SDG diet for a total of 6 wks. Within each arm, mice received 3 weekly injections of 0.9% saline or a combination of DOX [8 mg/(kg.wk)] and TRZ [3 mg/(kg.wk)] starting at the end of week 3. The main outcome was to evaluate the effects of FLX, ALA, and SDG on cardiovascular remodeling and markers of apoptosis, inflammation, and mitochondrial dysfunction. Significance between measurements was determined using a 4 (diet) × 2 (chemotherapy) × 2 (time) mixed factorial design with repeated measures.

RESULTS
In the RC + DOX + TRZ-treated mice at week 6 of the study, the left ventricular ejection fraction (LVEF) decreased by 50% compared with the baseline LVEF (P < 0.05). However, the prophylactic administration of the FLX, ALA, or SDG diet was partially cardioprotective, with mice in these treatment groups showing an ∼68% increase in LVEF compared with the RC + DOX + TRZ-treated group at week 6 (P < 0.05). Although markers of inflammation (nuclear transcription factor κB), apoptosis [poly (ADP-ribose) polymerase-1 and the ratio of BCL2-associated X protein to B-cell lymphoma-extra large], and mitochondrial dysfunction (BCL2-interacting protein 3) were significantly elevated by approximately 2-fold following treatment with RC + DOX + TRZ compared with treatment with RC + saline at week 6, prophylactic administration of FLX, ALA, or SDG partially downregulated these signaling pathways.

CONCLUSION
In a chronic in vivo female C57BL/6 mouse model of DOX + TRZ-mediated cardiotoxicity, FLX, ALA, and SDG were partially cardioprotective.

Asselin|Chantal Y|CY|
Lam|Amy|A|
Cheung|David Y C|DYC|
Eekhoudt|Cameron R|CR|
Zhu|Antonia|A|
Mittal|Ishika|I|
Mayba|Andrew|A|
Solati|Zahra|Z|
Edel|Andrea|A|
Austria|J Alejandro|JA|
Aukema|Harold M|HM|
Ravandi|Amir|A|
Thliveris|James|J|
Singal|Pawan K|PK|
Pierce|Grant N|GN|
Niraula|Saroj|S|
Jassal|Davinder S|DS|

flaxseed
cardiotoxicity
doxorubicin
cardio-oncology
heart failure
murine echocardiography


Correlation of pulmonary vein reconnection patterns after cryoballoon and duty-cycled ablation of atrial fibrillation with the time of arrhythmia recurrence.

Abstract:
Background
Pulmonary vein isolation (PVI) is safe and effective in the treatment of atrial fibrillation (AF). We compare and correlate pulmonary vein (PV) reconnection patterns at repeat ablation in patients with recurrent AF after PVI using duty-cycled radiofrequency (RF) technology (PVAC) or second-generation cryoballoon (CB) with the time of AF recurrence.

Methods and Results
In total, 85 PVAC and 66 CB patients undergoing a second ablation were enrolled 9.7 ± 3.4 months after initial PVI. PV reconnections were comparably high between both groups (93% PVAC and 92% CB patients). A mean of 2.79 ± 1.2 PVs/patient were reconnected after PVAC PVI compared with 1.97 ± 0.8 in CB patients, P < .0001. 33% PVAC patients, but no CB patient had 4 reconnected PVs (P < .0001). Early AF recurrences were more frequently observed in PVAC patients with ≥2 reconnected PVs, in CB patients with ≥3 reconnected PVs (both P < .01) and patients without PV reconnection, irrespective of the ablation technique. One reconnected PV was associated with late AF recurrence only in CB patients. The correlation between number of reconnected PVs and time of AF recurrence was -0.32 for PVAC and -0.52 for CB.

Conclusions
CB PVI was associated with greater durability and lesser PV reconnections/patient. There were negative correlations for both devices between extent of PV reconnections and time of AF recurrence. CB patients with early AF recurrences- although less frequently observed compared with PVAC patients had more reconnected PVs than PVAC patients, suggesting additional effects for AF prevention after CB PVI.

pulmonary vein reconnection
cryoballoon
pulmonary vein isolation
atrial fibrillation recurrence
duty‐cycled radiofrequency


Fungal Biorecovery of Gold From E-waste.

Abstract: Waste electric and electronic devices (e-waste) represent a source of valuable raw materials of great interest, and in the case of metals, e-waste might become a prized alternative source. Regarding gold, natural ores are difficult to mine due to their refractory nature and the richest ores have almost all been exploited. Additionally, some gold mining areas are present in geopolitically unstable regions. Finally, the gold mining industry produces toxic compounds, such as cyanides. As a result, the gold present in e-waste represents a nonnegligible resource (urban mining). Extraction methods of gold from natural ores (pyro- and hydrometallurgy) have been adapted to this particular type of matrix. However, to propose novel approaches with a lower environmental footprint, biotechnological methods using microorganisms are being developed (biometallurgy). These processes use the extensive metabolic potential of microbes (algae, bacteria, and fungi) to mobilize and immobilize gold from urban and industrial sources. In this review, we focus on the use of fungi for gold biomining. Fungi interact with gold by mobilizing it through mechanical attack as well as through biochemical leaching by the production of cyanides. Moreover, fungi are also able to release Au through the degradation of cyanide from aurocyanide complexes. Finally, fungi immobilize gold through biosorption, bioaccumulation, and biomineralization, in particular, as gold nanoparticles. Overall, the diversity of mechanisms of gold recycling using fungi combined with their filamentous lifestyle, which allows them to thrive in heterogeneous and solid environments such as e-waste, makes fungi an important bioresource to be harnessed for the biorecovery of gold.

Bindschedler|Saskia|S|
Vu Bouquet|Thi Quynh Trang|TQT|
Job|Daniel|D|
Joseph|Edith|E|
Junier|Pilar|P|

E-waste
Biometallurgy
Biomining
Gold nanoparticles
Gold recycling
Geomycology


Differential price-responsiveness of smoking behaviors among non-Hispanic African Americans and non-Hispanic whites in the United States.

Abstract:
BACKGROUND AND AIMS
Non-Hispanic African Americans (African Americans) smoke fewer cigarettes per day (CPD) and are more likely to be non-daily smokers than non-Hispanic whites (whites). Little is known about how changes in cigarette prices might contribute to these differences. This study aimed to measure the price-responsiveness of smoking participation, non-daily smoking among current smokers and smoking intensity among daily or non-daily smokers for African Americans and compare the price-responsiveness estimates with those for whites.

DESIGN
Analysis of data from the 2009-14 National Adult Tobacco Surveys and cigarette price data from the Tax Burden on Tobacco report.

SETTING
United States.

PARTICIPANTS
A total of 19 232 African American and 197 939 white adults aged 18+.

MEASUREMENTS
We used a three-part econometric model of cigarette demand to estimate the price-responsiveness of smoking participation, daily versus non-daily smoking and smoking intensity. The model controlled for secular variation, state-level anti-smoking sentiment and smoke-free air laws and socio-demographics.

FINDINGS
In 2009-14, 20.2% of African Americans and 17.7% of whites identified as current smokers; 70.2% of African American smokers and 81.4% of white smokers smoked daily. The price elasticity of smoking participation was significant for whites at -0.16 [95% confidence interval (CI) = -0.23, -0.09], indicating that a 10% increase in prices would reduce smoking participation by 1.6%, but not statistically significant for African Americans, and this racial/ethnic differential price responsiveness was not statistically significant. The price elasticity of smoking intensity was statistically significant for African American daily smokers at -0.29 (95% CI = -0.42, -0.16), but not statistically significant for white daily smokers, and this racial/ethnic differential price-responsiveness was statistically significant. The price elasticity of daily versus non-daily smoking among current smokers, and the price elasticity of smoking intensity among non-daily smokers were not statistically significant for either racial/ethnic group.

CONCLUSION
In the United States, cigarette price increases may have stronger effects on decreasing daily smokers' consumption among African Americans than among non-Hispanic whites.

African Americans
whites
cigarette price
price elasticity
daily and non-daily smoking
three-part model


Transmantle and transvenous pressure gradients in cerebrospinal fluid disorders.

Abstract: Hydrocephalus is the symptomatic endpoint of a variety of disease processes. Simple hydrodynamic models have failed to explain the entire spectrum of cerebrospinal fluid (CSF) disorders. Physical principles argue that for ventricles to expand, they must be driven by a force, Fishman's transmantle pressure gradient (TMPG). However, the literature to date, reviewed herein, is heterogenous and fails to consistently measure a TMPG. The venous system, like CSF, traverses the cerebral mantle, and thus analogous transparenchymal and transvenous pressure gradients have been described, reliant on the differential haemodynamics of the deep and superficial venous systems. Interpreting CSF disorders through these models provides new insights into the possible pathophysiological mechanisms underlying these diseases. However, until more sophisticated testing is performed, these models should remain heuristics.

Transmantle Transvenous Hydrocephalus CSF IIH


Modulation of muscle-tendon interaction in the human triceps surae during an energy dissipation task.

Abstract: The compliance of elastic elements allows muscles to dissipate energy safely during eccentric contractions. This buffering function is well documented in animal models but our understanding of its mechanism in humans is confined to non-specific tasks, requiring a subsequent acceleration of the body. The present study aimed to examine the behaviour of the human triceps surae muscle-tendon unit (MTU) during a pure energy dissipation task, under two loading conditions. Thirty-nine subjects performed a single-leg landing task, with and without added mass. Ultrasound measurements were combined with three-dimensional kinematics and kinetics to determine instantaneous length changes of MTUs, muscle fascicles, Achilles tendon and combined elastic elements. Gastrocnemius and soleus MTUs lengthened during landing. After a small concentric action, fascicles contracted eccentrically during most of the task, whereas plantar flexor muscles were activated. Combined elastic elements lengthened until peak ankle moment and recoiled thereafter, whereas no recoil was observed for the Achilles tendon. Adding mass resulted in greater negative work and MTU lengthening, which were accompanied by a greater stretch of tendon and elastic elements and a greater recruitment of the soleus muscle, without any further fascicle strain. Hence, the buffering action of elastic elements delimits the maximal strain and lengthening velocity of active muscle fascicles and is commensurate with loading constraints. In the present task, energy dissipation was modulated via greater MTU excursion and more forceful eccentric contractions. The distinct strain pattern of the Achilles tendon supports the notion that different elastic elements may not systematically fulfil the same function.

Werkhausen|Amelie|A|0000-0002-3194-2282
Albracht|Kirsten|K|
Cronin|Neil J|NJ|
Meier|Rahel|R|
Bojsen-Møller|Jens|J|
Seynnes|Olivier R|OR|

Achilles tendon
Energy absorption
Mechanical buffer