Sustainable Cleft Care: A Comprehensive Model Based on the Global Smile Foundation Experience.

Abstract:
INTRODUCTION
Clefts of the lip and palate are leading congenital facial anomalies. Underserved patients with these facial differences lack access to medical care, surgical expertise, prenatal care, or psychological support. Moreover, the disease results in significant economic strains on patients and their families. While surgical outreach programs have attempted to fill this void, significant challenges facing international comprehensive cleft care persist.

OBJECTIVE
Propose a path toward international sustainable cleft care based on the Global Smile Foundation experience.

RESULTS
International sustainable comprehensive cleft care can be achieved by regulating surgical outreach programs. Regulation of these missions would ensure standardized care and encourage stakeholders to cooperate and adequately allocate funding and resources. Capacity building can be achieved through "diagonal" cleft care delivery models, multidisciplinary workshops, fellowship programs, research and quality assurance, as well as leveraging emerging technologies such as Augmented Reality.

CONCLUSION
International comprehensive cleft care requires continuous collaborative efforts between visiting and local teams as well as international and national organizations. Standardizing and regulating current practices as well as promoting capacity building initiatives can contribute to sustainable cleft care.

Chahine|Elsa M|EM|0000-0002-4140-201X
Kantar|Rami S|RS|0000-0002-2245-2054
Kassam|Serena N|SN|0000-0001-5418-3568
Vyas|Raj M|RM|
Ghotmi|Lilian H|LH|
Haddad|Anthony G|AG|0000-0001-6698-2439
Hamdan|Usama S|US|

D002971:Cleft Lip
D002972:Cleft Palate
D006801:Humans

sustainability
outreach programs
missions
capacity building
augmented reality
cleft lip and palate
cleft workshops
global surgery


High-Quality Resolution of the Outbreak-Related Zika Virus Genome and Discovery of New Viruses Using Ion Torrent-Based Metatranscriptomics.

Abstract: Arboviruses, including the Zika virus, have recently emerged as one of the most important threats to human health. The use of metagenomics-based approaches has already proven valuable to aid surveillance of arboviral infections, and the ability to reconstruct complete viral genomes from metatranscriptomics data is key to the development of new control strategies for these diseases. Herein, we used RNA-based metatranscriptomics associated with Ion Torrent deep sequencing to allow for the high-quality reconstitution of an outbreak-related Zika virus (ZIKV) genome (10,739 nt), with extended 5'-UTR and 3'-UTR regions, using a newly-implemented bioinformatics approach. Besides allowing for the assembly of one of the largest complete ZIKV genomes to date, our strategy also yielded high-quality complete genomes of two arthropod-infecting viruses co-infecting C6/36 cell lines, namely: Alphamesonivirus 1 strain Salvador (20,194 nt) and Aedes albopictus totivirus-like (4618 nt); the latter likely represents a new viral species. Altogether, our results demonstrate that our bioinformatics approach associated with Ion Torrent sequencing allows for the high-quality reconstruction of known and unknown viral genomes, overcoming the main limitation of RNA deep sequencing for virus identification.

Zika virus
metatranscriptomics
Ion Torrent
RNA deep sequencing
virus identification


Synthesis of functionalized fluorescent silver nanoparticles and their toxicological effect in aquatic environments (Goldfish) and HEPG2 cells.

Abstract: Silver nanoparticles, AgNPs, are widely used in our daily life, mostly due to their antibacterial, antiviral, and antifungal properties. However, their potential toxicity remains unclear. In order to unravel this issue, emissive AgNPs were first synthetized using an inexpensive photochemical method, and then their permeation was assessed in vivo in goldfish and in vitro in human hepatoma cells (HepG2). In addition, the oxidative stress caused by AgNPs was assessed in enzymes such as glutathione-S-transferase (GST), catalase (CAT), and in lipid peroxidation (LPO). This study demonstrates that the smallest sized AgNPs@3 promote the largest changes in gold fish livers, whereas AgNPs@1 were found to be toxic in HEPG2 cells depending on both the size and functionalized/stabilizer ligand.

Oliveira|Elisabete|E|
Santos|Hugo M|HM|
Garcia-Pardo|Javier|J|
Diniz|Mário|M|
Lorenzo|Julia|J|
Rodríguez-González|Benito|B|
Capelo|José L|JL|
Lodeiro|Carlos|C|

fluorescence
silver nanoparticles
goldfish
human hepatoma cells
cytotoxicity


Surface Studies on Glass Powders Used in Commercial Glass-Ionomer Dental Cements.

Abstract: The surface properties of three commercial ionomer glass powders, i.e., Fuji IX, Kavitan Plus and Chemadent G-J-W were studied. Samples were analyzed by X-ray fluorescence spectroscopy (XRF), and the density was determined by gas pycnometry. Morphology was studied using scanning electron microscopy (SEM) and laser diffraction (LD) technique, whereas low-temperature nitrogen sorption measurements determined textural parameters like specific surface area and pore volume. Thermal transformations in the materials studied were evaluated by thermogravimetric analysis (TGA), which was carried out in an inert atmosphere between 30 °C and 900 °C. XRF showed that Fuji IX and Kavitan Plus powders were strontium-based, whereas Chemadent G-J-W powder was calcium-based. Powders all had a wide range of particle sizes under SEM and LD measurements. Specific surface areas and pore volumes were in the range 1.42-2.73 m2/g and 0.0029 to 0.0083 cm3/g, respectively, whereas densities were in the range 2.6428-2.8362 g/cm3. Thermogravimetric analysis showed that the glass powders lost mass in a series of steps, with Fuji IX powder showing the highest number, some of which are attributed to the dehydration and decomposition of the polyacrylic acid present in this powder. Mass losses were more straightforward for the other two glasses. All three powders showed distinct losses at around 780 °C and 835 °C, suggesting that similar dehydration steps occur in all these glasses. Other steps, which differed between glass powders, are attributed to variations in states of water-binding on their surfaces.

surface properties
ionomer glasses
density
thermogravimetric analysis
particles morphology


Stable contrast mode on TiO2(110) surface with metal-coated tips using AFM.

Abstract: We investigated a method to obtain a stable contrast mode on the TiO2(110) surface. The stable contrast rate is approximately 95% with a W-coated Si cantilever, which demonstrates that a stable tip apex plays an important role to obtain the real geometry of the surface during atomic force microscopy measurement. Information related to surface structure and tunnelling current on the TiO2(110) surface can be obtained by the W-coated Si cantilever. It is possible to investigate the electronic structure and surface potential on the TiO2(110) surface with atomic resolution. In particular, the proposed method could be widely applied to investigate the catalytic activity and the mechanism of a catalytic reaction by a metal-coated tip in the future.

Li|Yan Jun|YJ|
Wen|Huanfei|H|
Zhang|Quanzhen|Q|
Adachi|Yuuki|Y|
Arima|Eiji|E|
Kinoshita|Yukinori|Y|
Nomura|Hikaru|H|
Ma|Zongmin|Z|
Kou|Lili|L|
Tsukuda|Yoshihiro|Y|
Naitoh|Yoshitaka|Y|
Sugawara|Yasuhiro|Y|
Xu|Rui|R|
Cheng|Zhihai|Z|

Stable contrast mode
Atomic force microscopy (AFM)
TiO(2)(110) surface


Candida tropicalis infection modulates the gut microbiome and confers enhanced susceptibility to colitis in mice.

Abstract:
BACKGROUND & AIMS
We previously showed that abundance of C. tropicalis is significantly greater in Crohn's disease patients compared to non-disease first-degree relatives. The aim of this study was to determine the effects and mechanisms of action of C. tropicalis infection on intestinal inflammation and injury in mice.

METHODS
C57BL/6 mice were inoculated with C. tropicalis, and colitis induced by administration of dextran sodium sulfate (DSS) in drinking water. Disease severity and intestinal permeability were subsequently evaluated by endoscopy, histology, RT-qPCR, as well as 16S rRNA and NanoString analyses.

RESULTS
Infected mice showed more severe colitis, with alterations in gut mucosal Th1 and Th17 cytokine expression, and an increased frequency of mesenteric lymph node (MLN)-derived group 2 innate lymphoid cells (ILC2s) compared to uninfected controls. Gut microbiome composition, including changes in the mucin-degrading bacteria, A. Muciniphila and R. Gnavus, was significantly altered, as was expression of several genes affecting intestinal epithelial homeostasis in isolated colonoids, after C. tropicalis infection compared to uninfected controls. In line with these findings, fecal microbiome transplantation (FMT) of germ-free (GF) recipient mice using infected vs. uninfected donors exhibited altered expression of several tight-junction proteins and increased susceptibility to DSS-induced colitis.

CONCLUSIONS
C. tropicalis induces dysbiosis that involves changes in the presence of mucin-degrading bacteria, leading to altered tight junction protein expression with increased intestinal permeability and followed by induction of robust Th1/Th17 responses, which ultimately lead to an accelerated pro-inflammatory phenotype in experimental colitic mice.

Di Martino|Luca|L|
De Salvo|Carlo|C|
Buela|Kristine-Ann|KA|
Hager|Christopher|C|
Ghannoum|Mahmoud|M|
Osme|Abdullah|A|
Buttò|Ludovica|L|
Bamias|Giorgos|G|
Pizarro|Theresa T|TT|
Cominelli|Fabio|F|

colitis
C. tropicalis
A. muciniphila
mycobiome


Effectiveness and Safety of Minimally Invasive Orthodontic Tooth Movement Acceleration: A Systematic Review and Meta-analysis.

Abstract: Doctors and patients attempt to accelerate orthodontic tooth movement with a minimally invasive surgery approach. The purpose of this systematic review was to evaluate the evidence of accelerated tooth movement in minimally invasive surgery and the adverse effects from it. A systematic search of the literature was performed in the electronic databases of PubMed, CENTRAL (Cochrane Central Register of Controlled Trials), Embase, Scopus, Web of Science, Science Direct, and Medline and was complemented by a manual search until February 2019. The inclusion criteria were prospective clinical studies of patients treated with a fixed appliance, and the intervention was accelerated orthodontic treatment with minimally invasive surgery. Nineteen articles (538 participants) were included in the review: 9 studies assessed the rate of upper canine movement; 5 considered the treatment time; 1 evaluated the en masse retraction time; and 4 studied adverse effects. We performed a meta-analysis for the rate of canine movement and treatment time and described the results for the adverse effects in a systematic review. The results of the subgroup analysis according to micro-osteoperforation and piezocision were included in the study. No accelerated tooth movement was found in the micro-osteoperforation group. After flapless corticotomy procedures, increased tooth movement rates were identified by weighted mean differences of 0.63 (95%CI = 0.22, 1.03, P = 0.003) and 0.64 (95% CI, -25 to 1.53; P = 0.16) for 1 and 2 mo, respectively. The mean treatment time was 68.42 d (95% CI, -113.19 to -23.65; P = 0.003) less that than for minimally invasive surgery. Moreover, no significant adverse effect was found. Because of the high heterogeneity of the meta-analysis, the results must be validated by additional large-sample multicenter clinical trials. There is not sufficient evidence to support that the single use of micro-osteoperforation could accelerate tooth movement, and there is only low-quality evidence to prove that flapless corticotomy could accelerate tooth movement.

Fu|T|T| Liu|S|S| Zhao|H|H| Cao|M|M| Zhang|R|R|

D019060:Minimally Invasive Surgical Procedures

minimally invasive surgery
accelerated tooth movement
orthodontics treatment
micro-osteoperforation
piezocision
corticotomy


Loss of Gadd45b accelerates BCR-ABL-driven CML.

Abstract: Gadd45b is a member of Gadd45 stress sensor protein family that also includes Gadd45a & Gadd45g. To investigate the effect of Gadd45b in bcr-abl oncogene driven chronic myeloid leukemia (CML) development, syngeneic wild type lethally irradiated mice were reconstituted with either wild type or Gadd45b null myeloid progenitors transduced with a retroviral vector expressing BCR-ABL. Loss of Gadd45b was observed to accelerate BCR-ABL driven CML development with shortened median mouse survival time. BCR-ABL Gadd45b deficient CML progenitors exhibited increased proliferation and decreased apoptosis, associated with hyper-activation of c-Jun NH2-terminal kinase and Stat5. These results provide novel evidence that gadd45b, like gadd45a, functions as a suppressor of BCR-ABL driven leukemia, albeit via a different mechanism.

Sha|Xiaojin|X|
Hoffman|Barbara|B|
Liebermann|Dan A|DA|

Gadd45a
chronic myelogenous leukemia
stress response protein
tumor suppressor


Chloroplast genomes of five Oedogonium species: genome structure, phylogenetic analysis and adaptive evolution.

Abstract:
BACKGROUND
The order Oedogoniales within the single family Oedogoniaceae comprised of three genera, Oedogonium, Oedocladium, and Bulbochaete based on traditional morphological criteria. While several molecular phylogenetic studies have suggested that both Oedogonium and Oedocladium may not be monophyletic, broader taxon sampling and large amounts of molecular data acquisition could help to resolve the phylogeny and evolutionary problems of this order. This study determined five chloroplast (cp) genomes of Oedogonium species and aimed to provide further information on cp genome for a better understanding of the phylogenetic and evolutionary relationships of the order Oedogoniales.

RESULTS
The five Oedogonium cp genomes showed typical quadripartite and circular structures, and were relatively conserved in their structure, gene synteny, and inverted repeats boundaries in general, except for small variation in genome sizes, AT contents, introns, and repeats. Phylogenetic analyses based on 54 cp protein-coding genes examined by maximum likelihood and Bayesian analyses using amino acid and nucleotide datasets indicated that both Oedocladium and Oedogonium are polyphyletic groups. A positively selected gene (psbA) was identified in the two Oedocladium species and the terrestrial Oedogonium species, indicating that terrestrial Oedogoniales taxa may have undergone adaptive evolution to adjust to the difference in light intensity between aquatic and terrestrial habitats.

CONCLUSIONS
Our results enrich the data on cp genomes of the genus Oedogonium. The availability of these cp genomes can help in understanding the cp genome characteristics and resolve phylogenetic and evolutionary relationships of the order Oedogoniales.

Xiong|Qian|Q| Hu|Yuxin|Y| Lv|Wenqi|W| Wang|Qinghua|Q| Liu|Guoxiang|G| Hu|Zhengyu|Z|

D001499:Bayes Theorem
D019143:Evolution, Molecular
D059646:Genome Size
D054628:Genome, Chloroplast
D010802:Phylogeny
D000073336:Whole Genome Sequencing

Chloroplast genome
Adaptive evolution
Oedogoniales
Synteny
Polyphyletic group


Outdoor physical activity, compliance with the physical activity, screen time, and sleep duration recommendations, and excess weight among adolescents.

Abstract:
Background
Spending time outdoor has been identified as an important way to achieve the physical activity required for maintaining and improving health and to lower sedentary time among young children. However, evidence of such relationships in adolescents is particularly limited. This study investigated the relationships between frequency of outdoor physical activity after school, compliance with the physical activity, screen time, and sleep duration recommendations, and overweight/obesity among adolescents.

Methods
A total of 10 028 middle and high school students (mean age of 15.2 y) self-reported the number of weekdays they spent physically active outdoors after school. Physical activity, screen time, sleep duration, height, and weight were self-reported. Logistic regression models for the total sample and stratified by sex were adjusted for important covariates.

Results
Overall, there was a positive gradient between the number of weekdays spent physically active outdoor after school and compliance with the physical activity (more than or equal to 60 min/day at moderate-to-vigorous intensity) and screen time (less than or equal to 2 h/day) recommendations while a negative gradient with overweight/obesity was observed. Significant sex differences were observed in the associations of outdoor physical activity after school with adherence to the sleep duration and physical activity recommendations. For example, outdoor physical activity after school on all 5 days was associated with greater odds of compliance with the sleep duration recommendation among males (OR = 1.53; 95% CI, 1.01-2.31), but not females (OR = 0.92; 95% CI, 0.65-1.30).

Conclusions
Results suggest that outdoor physical activity after school could be a behavioural target to increase compliance with the physical activity and screen time recommendations and to possibly tackle excess weight among adolescents.

obesity
exercise
movement behaviours
outdoor time


Near-critical GLUT1 and Neurodegeneration.

Abstract: Recent articles have drawn renewed attention to the housekeeping glucose transporter GLUT1 and its possible involvement in neurodegenerative diseases. Here we provide an updated analysis of brain glucose transport and the cellular mechanisms involved in its acute modulation during synaptic activity. We discuss how the architecture of the blood-brain barrier and the low concentration of glucose within neurons combine to make endothelial/glial GLUT1 the master controller of neuronal glucose utilization, while the regulatory role of the neuronal glucose transporter GLUT3 emerges as secondary. The near-critical condition of glucose dynamics in the brain suggests that subtle deficits in GLUT1 function or its activity-dependent control by neurons may contribute to neurodegeneration. © 2017 Wiley Periodicals, Inc.

Barros|L Felipe|LF|
San Martín|Alejandro|A|
Ruminot|Ivan|I|
Sandoval|Pamela Y|PY|
Fernández-Moncada|Ignacio|I|
Baeza-Lehnert|Felipe|F|
Arce-Molina|Robinson|R|
Contreras-Baeza|Yasna|Y|
Cortés-Molina|Francisca|F|
Galaz|Alex|A|
Alegría|Karin|K|

glucose transporter
Alzheimer disease
GLUT1 deficiency
Slc2a1
astrocyte
endothelium


Surgical repair of tetralogy of Fallot using autologous right atrial appendages: short- to mid-term results.

Abstract:
OBJECTIVES
The prevention of pulmonary insufficiency (PI) is a crucial part of the tetralogy of Fallot repair. Many techniques have been introduced to construct valves from different materials for the right ventricular outflow tract, including the most commonly constructed monocusp valves. We are introducing a new bicuspid valve made intraoperatively using the autologous right atrial appendage (RAA) to prevent PI in these patients.

METHODS
The RAA valve was constructed and used in 21 patients with tetralogy of Fallot. The effective preservation of the native valve was impossible in all patients because of either a severe valve deformity or a small annulus. The RAA valve was created after ventricular septal defect closure and right ventricular outflow tract myectomy and was covered with a bovine transannular pericardial patch. The perioperative data were evaluated, and the echocardiography results were assessed immediately after operations and in follow-up with a median of 10.5 months. The data were retrospectively compared with 10 other patients with similar demographic data but with only transannular patches.

RESULTS
The mean age of the patients was 13.3 months. No mortality or related morbidity occurred after repair using the RAA valve. The PI severity early after the operation was trivial or no PI in 18 patients, and mild PI was observed in 3 patients, which progressed to moderate PI in one of them in the mean 12-month follow-up period. Fifteen patients had mild or no pulmonary stenosis, while moderate pulmonary stenosis was observed in 6 others. Compared with the other 10 patients with only transannular patches, the RAA valve patients had prolonged operative and clamping times, but no difference in postoperative course and shorter hospital stays. The degree of PI was, of course, significantly less in the RAA valve patients, but pulmonary stenosis was the same.

CONCLUSIONS
The RAA valve construction is a safe and effective technique to prevent PI after the tetralogy of Fallot repair, at least in terms of short- and mid-term results. A longer follow-up period is needed to confirm if this new valve can eliminate or significantly delay the need for pulmonary valve replacement in these patients.

Amirghofran|Ahmadali|A| Edraki|Fatemeh|F| Edraki|Mohammadreza|M| Ajami|Gholamhossein|G| Amoozgar|Hamid|H| Mohammadi|Hamid|H| Emaminia|Abbas|A| Ghasemzadeh|Bahram|B| Borzuee|Mohammad|M| Peiravian|Farah|F| Kheirandish|Zahra|Z| Mehdizadegan|Nima|N| Sabri|Mohammadreza|M| Cheriki|Sirus|S| Arabi|Hamid|H|

Tetralogy of Fallot
Right atrial appendage
Pulmonary insufficiency
Transannular patch


Preparation and Application of Cell Membrane-Camouflaged Nanoparticles for Cancer Therapy.

Abstract: Cancer is one of the leading causes of death worldwide. Many treatments have been developed so far, although effective, suffer from severe side effects due to low selectivity. Nanoparticles can improve the therapeutic index of their delivered drugs by specifically transporting them to tumors. However, their exogenous nature usually leads to fast clearance by mononuclear phagocytic system. Recently, cell membrane-camouflaged nanoparticles have been investigated for cancer therapy, taking advantages of excellent biocompatibility and versatile functionality of cell membranes. In this review, we summarized source materials and procedures that have been used for constructing and characterizing biomimetic nanoparticles with a focus on their application in cancer therapy.

Zhai|Yihui|Y| Su|Jinghan|J| Ran|Wei|W| Zhang|Pengcheng|P| Yin|Qi|Q| Zhang|Zhiwen|Z| Yu|Haijun|H| Li|Yaping|Y|

Nanoparticle
Cell membrane
Camouflage
Cancer.


Complete mitochondrial genome of Lelecella limenitoides (Lepidoptera: Nymphalidae: Apaturinae) and phylogenetic implication.

Abstract: The length of Lelecella limenitoides complete mitogenome was 15,203 bp and contained the typical gene arrangement, base composition, and codon usage found in other related species. The overall base composition exhibited obvious anti-G (7.5%) and AT bias (81.6%). The initiation codons of all PCGs were typical ATN (ATA/ATG/ATT), and the termination codons were TAA, TAG, or incomplete stop codon T-. All tRNAs could be folded into typical cloverleaf secondary structures, except tRNASer (AGN). Phylogenetic analysis showed that L. limenitoides was clustered with the clade of Sasakia, Euripus, and Apatura.

Fang|Li Jun|LJ|
Mao|Shao Li|SL|
Zhang|Ya Lin|YL|

mitochondrial genome
Lelecella limenitoides
Apaturinae
phylogeny


Detection of twin pregnancies in ewes by pregnancy-associated glycoprotein assay and transabdominal ultrasonography.

Abstract: The objectives of the present study were to evaluate and compare the accuracy of transabdominal ultrasonography and pregnancy-associated glycoprotein (PAG) assay in the diagnosis of twin pregnancies in ewes and to evaluate the utility of the PAG assay for predicting fetal gender in singleton pregnancies. The animals in the study consisted of 179 pregnant ewes. The number of fetuses in the ewe was determined using transabdominal ultrasonography between days 40 and 60 (on days 40, 45, 50, 55, and 60). Blood samples were collected from all the ewes on the same day to determine the PAG concentrations. The results found were highly sensitive for the detection of twin pregnancies by transabdominal ultrasonography. The accuracy of transabdominal ultrasonography in detecting twin pregnancies was found to be higher on day 60 than on other days (P < 0.05). The sensitivities of PAG assay in detecting twin pregnancies on days 40, 45, 50, 55, and 60 were 91.67%, 66.67%, 81.82%, 88.89%, and 33.33%, respectively. The accuracies of the PAG assay in detecting twin pregnancies on days 40, 45, and 50 were found to be statistically significant higher than other days (P < 0.05). The PAG assay had low sensitivity and specificity for predicting fetal gender. It was concluded that twin pregnancies in ewes can be diagnosed with high accuracy using transabdominal ultrasonography on day 60 of pregnancy and as well as using the PAG assay during the early days of pregnancy (on days 40, 45, and 50). The PAG assay is not useful for predicting fetal gender.

Alkan|H|H|
Kivrak|M B|MB|
Satilmis|F|F|
Tekindal|M A|MA|
Dinc|D A|DA|

Ultrasonography
PAG
Fetal gender
Multiple pregnancy
Sheep


Priapism as the initial symptom of primary penile lymphoma: A case report.

Abstract: Primary penile lymphoma presenting with priapism as the initial symptom is extremely rare. In total, <10 cases have been previously reported. The diagnosis can be difficult and patients often develop metastasis. The current study reports the case of a 48-year-old male, who presented with a one-month history of painless priapism. On admission to Yantai Yuhuangding Hospital Affiliated to Qingdao University (Yantai, China), examination revealed an erect penis, enlarged lymph nodes in the bilateral inguinal and swelling in the thighs. A biopsy was taken from the right inguinal lymph node and the pathological diagnosis confirmed a diffuse large B-cell type of non-Hodgkin's lymphoma, while an enhanced computed tomography scan of the chest revealed evidence of the invasion of malignant lymphoma cells. Priapism disappeared two days following the completion of the first cycle of chemotherapy with the E-CHOP regimen (cyclophosphamide, vincristine, prednisone, epirubicin and etoposide); however, evidence of brain metastases was observed one month later, which was confirmed by magnetic resonance imaging. The patient received cranial radiotheraphy and systemic treatment for cerebral edema. The patient did not respond well to treatment and succumbed to the disease three months following the initial diagnosis of lymphoma. Lymphoma may be difficult to diagnose, depending on the initial symptoms; therefore, the patient history must be carefully assessed so as to determine an early diagnosis and prevent metastasis, thus improving the prognostic outcome.

Gong|Zhaohua|Z| Zhang|Ying|Y| Chu|Hongjin|H| Lian|Peiwen|P| Zhang|Liangming|L| Sun|Ping|P| Chen|Jian|J|

priapism
primary penile lymphoma
metastasis


Down-regulated miR-28-5p in human hepatocellular carcinoma correlated with tumor proliferation and migration by targeting insulin-like growth factor-1 (IGF-1).

Abstract: Hepatocellular carcinoma (HCC) is a rapidly progressing, incurable cancer that frequently spreads to portal vein and lung. New insights are needed to identify therapeutic targets to prevent or retard HCC metastatic progression. Because microRNAs (miRNA) often act as tumor regulators, we investigated their role in preclinical models of HCC. Here we found miR-28-5p is a liver-relevant anti-proliferative miRNA whose expression, functions, and mechanisms were analyzed in human hepatoma cells, HepG2 and Huh7. Interestingly, when evaluating the specific targets of miR-28-5p, we found that ectopic miR-28-5p expression down-regulates insulin-like growth factor 1 (IGF1) protein and that the expression of miR-28-5p correlates negatively with IGF1 protein in HCC cells. Luciferase report in HCC cells expressing miR-28-5p suggests that miR-28-5p reduces luciferase activity by targeting the 3'-UTR of IGF1 mRNA. Additionally, we show that the selective inhibition of either the PI3K/AKT pathway prior to miR-28-5p stimulation prevents the expression of previously described tumor suppressor miRNAs that are family and cluster specific. Together, our results defined miR-28-5p as a critical regulator of IGF1 mRNA translation function, down-regulated miR-28-5p in HCC was associated with tumor growth through PI3K/AKT pathway by targeting IGF1. miR-28-5p-IGF1-PI3K/AKT pathway may play an important role in the development of HCC.

D015972:Gene Expression Regulation, Neoplastic


Long-Term Safety and Efficacy of Single or Repeated Intra-Articular Injection of Allogeneic Neonatal Mesenchymal Stromal Cells for Managing Pain and Lameness in Moderate to Severe Canine Osteoarthritis Without Anti-inflammatory Pharmacological Support: Pilot Clinical Study.

Abstract: Objective: To explore the long-term safety and efficacy of canine allogeneic mesenchymal stromal cells (MSC) administered intra-articularly as single or repeated injections in appendicular joints of dogs affected by moderate to severe refractory osteoarthritis. Study Design: 22 pet dogs were recruited into a non-randomized, open and monocentric study initially administering one cellular injection. A second injection was offered after 6 months to owners if the first injection did not produce expected results. Materials and Methods: Anti-inflammatory treatment (if prescribed) was discontinued at last one week before the onset of treatment. Each injection consisted of at least 10 million viable neonatal allogeneic mesenchymal stromal cells obtained from fetal adnexa. Medical data was collected from veterinary clinical evaluations of joints up to 6 months post-injection and owner's assessment of their dog's mobility and well-being followed for a further 2 years when possible. Results: Mild, immediate self-limiting inflammatory joint reactions were observed in 5/22 joints after the first injection, and in almost all dogs having a subsequent injection. No other MSC-related adverse medical events were reported, neither during the 6 months follow up visits, nor during the long-term (2-years) safety follow up. Veterinary clinical evaluation showed a significant and durable clinical improvement (up to 6 months) following MSC administration. Eight dogs (11 joints) were re-injected 6 months apart, sustaining clinical benefits up to 1 year. Owner's global satisfaction reached 75% at 2 years post-treatment Conclusion: Our data suggest that a single or repeated intra-articular administration of neonatal MSC in dogs with moderate to severe OA is a safe procedure and confer clinical benefits over a 24-month period. When humoral response against MSC is investigated by flow cytometry, a positive mild and transient signal was detected in only one dog from the studied cohort, this dog having had a positive clinical outcome.

Cabon|Quentin|Q| Febre|Marine|M| Gomez|Niels|N| Cachon|Thibaut|T| Pillard|Paul|P| Carozzo|Claude|C| Saulnier|Nathalie|N| Robert|Clément|C| Livet|Véronique|V| Rakic|Rodolphe|R| Plantier|Nadia|N| Saas|Philippe|P| Maddens|Stéphane|S| Viguier|Eric|E|

allogeneic
lameness
osteoarthritis
dogs
NSAID
long-term follow up
mesenchymal stem/stromal cell
neonatal stem cell


Meta-Analysis of Milk Consumption and the Risk of Cognitive Disorders.

Abstract: The association between milk intake and cognitive disorders has been investigated in several epidemiological studies, but the findings are still conflicting. No quantitative assessment has been performed to evaluate the potential relationship of milk intake and cognitive disorders. From the inception to October 2016, the PubMed and the Embase databases were searched for observational studies reporting the association of milk consumption and cognitive disorders (Alzheimer's disease, dementia, and cognitive decline/impairment). A generic inverse-variance random-effects method was used to pool the Odds Ratios (ORs) and corresponding 95% confidence intervals (CIs) for the highest compared with the lowest level of milk intake. Subgroup and meta-regression analyses were used to assess the heterogeneity between subgroups. We identified seven articles involving a total of 10,941 participants. The highest level of milk consumption was significantly associated with a decreased risk of cognitive disorders, and the pooled OR (95% CI) was 0.72 (0.56, 0.93), with evidence of significant heterogeneity (I² = 64%, p = 0.001). Subgroup analysis indicated that the association was more pronounced in ischemic stroke patients based on a single study. Furthermore, the inverse association between milk intake and cognitive disorders was limited to Asian subjects, and the African populations showed an intermediate non-significant trend. Although we have obtained a significant association, an established relationship cannot be drawn due to the study limitation. Large prospective studies are needed to quantify the potential dose-response patterns of milk intake and to explore the association in populations with different characteristics.

meta-analysis
cognitive disorders
milk intake
dementia
cognitive decline
Alzheimer’s disease


A Network Meta-Analysis of Cancer Immunotherapies Versus Chemotherapy for First-Line Treatment of Patients With Non-Small Cell Lung Cancer and High Programmed Death-Ligand 1 Expression.

Abstract: In the absence of head-to-head trials of first-line treatments for metastatic non-small cell lung cancer (NSCLC), synthesis of available evidence is needed. We conducted a systematic literature review and network meta-analysis of randomized controlled trials in patients with stage IV NSCLC and high programmed death-ligand 1 (PD-L1) expression. Patients with other-stage NSCLC or without PD-L1 expression and populations with < 80% stage IV NSCLC were excluded. Outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events. English records from MEDLINE and Embase published through October 2020 were eligible, supplemented by hand searches of other sources. Three evidence networks were constructed based on histology (mixed, squamous, non-squamous). OS and PFS results were analyzed applying Bayesian fractional polynomial random-effects models. Hazard ratios over time with 95% credible intervals (CrIs) and expected differences in OS and PFS between each cancer immunotherapy regimen and the chemotherapy common comparator were generated. Seventeen clinical trials were included after screening 32,527 records. Heterogeneity and risk of bias were generally low across trials. In the mixed-histology network of PD-L1-high patients, expected OS was significantly longer with atezolizumab (estimated difference: 10.4 months [95% CrI: 1.9, 18.2]), pembrolizumab (7.2 [2.2, 12.3]), and cemiplimab (13.0 [4.2, 21.0]) versus chemotherapy but not with nivolumab (3.5 [-2.5, 10.6]) or nivolumab plus ipilimumab (6.7 [-0.5, 14.2]) versus chemotherapy. OS improvements were not significant compared with chemotherapy for any regimen in the squamous and non-squamous networks, except pembrolizumab plus chemotherapy in the non-squamous network. All regimens showed significantly longer expected PFS versus chemotherapy in the non-squamous network, whereas the increases were not significant in the mixed or squamous networks. ORR was significantly higher with pembrolizumab and cemiplimab versus chemotherapy in the mixed-histology network, with sintilimab in the non-squamous network, and with combination regimens, including pembrolizumab or atezolizumab, in the squamous and non-squamous networks, except with atezolizumab plus carboplatin, paclitaxel, and bevacizumab. Survival and safety versus chemotherapy were generally similar across cancer immunotherapies and histology networks. These findings may support treatment decisions for patients with high PD-L1 status receiving first-line treatment for NSCLC.

Herbst|Roy|R|
Jassem|Jacek|J|
Abogunrin|Seye|S|
James|Daniel|D|
McCool|Rachael|R|
Belleli|Rossella|R|
Giaccone|Giuseppe|G|
De Marinis|Filippo|F|

meta-analysis
immunotherapy
non-small cell lung cancer
atezolizumab
pembrolizumab
nivolumab
ipilimumab


Mechanism, stability and fitness cost of resistance to pyriproxyfen in the house fly, Musca domestica L. (Diptera: Muscidae).

Abstract: Pyriproxyfen, a bio-rational insecticide, used worldwide for the management of many insect pests including the house fly, Musca domestica. To devise a retrospective resistance management strategy, biological parameters of pyriproxyfen resistant (Pyri-SEL), unselected (UNSEL), Cross1 and Cross2M. domestica strains were studied in the laboratory. Additionally, the stability and mechanism of resistance was also investigated. After 30 generations of pyriproxyfen selection, a field-collected strain developed 206-fold resistance compared with susceptible strain. Synergists such as piperonyl butoxide and S,S,S-tributylphosphorotrithioate did not alter the LC50 values, suggesting another cause of target site resistance to pyriproxyfen in the Pyri-SEL strain. The resistance to all tested insecticides was unstable in Pyri-SEL strain. The relative fitness of 0.51 with lower fecundity, hatchability, lower number of next generation larvae, reduced mean population growth rate and net reproductive rate were observed in the Pyri-SEL strain compared with the UNSEL strain. The cost of fitness associated with pyriproxyfen resistance was evident in Pyri-SEL strain. The present study provides useful information for making pro-active resistance management strategies to delay resistance development.

Shah|Rizwan Mustafa|RM|
Shad|Sarfraz Ali|SA|
Abbas|Naeem|N|

Resistance
Relative fitness
Biotic potential
Insect growth regulator


Attachment insecurity mediates the relationship between childhood trauma and eating disorder psychopathology in a clinical sample: a structural equation model.

Abstract:
OBJECTIVES
Childhood maltreatment occurs often among those with an eating disorder and is considered a nonspecific risk factor. However, the mechanisms by which childhood maltreatment may lead to an eating disorder are not well understood. The current study tests a model in which attachment insecurity is hypothesized to mediate the relationship between childhood maltreatment and eating disorder psychopathology.

METHOD
Treatment seeking adults with eating disorders (N=308) completed questionnaires about childhood maltreatment, eating disorder psychopathology, and adult attachment.

RESULTS
Structural equation models indicated that childhood trauma had a direct effect on eating disorder symptoms. Also, attachment anxiety and avoidance each equally mediated the childhood maltreatment to eating disorder psychopathology relationship.

CONCLUSIONS
Attachment insecurity, characterized by affect dysregulation and interpersonal sensitivities may help to explain why eating disorder symptoms may be one consequence of childhood maltreatment in a clinical sample. Clinicians treating primarily those with trauma might assess for disordered eating as a potential manifestation of the sequelae of trauma and attachment insecurity.

Tasca|Giorgio A|GA|
Ritchie|Kerri|K|
Zachariades|Fotini|F|
Proulx|Genevieve|G|
Trinneer|Anne|A|
Balfour|Louise|L|
Demidenko|Natasha|N|
Hayden|Genevieve|G|
Wong|Alison|A|
Bissada|Hany|H|

Attachment
Trauma
Eating disorders
Structural equation modeling
Childhood maltreatment
Child abuse and trauma scale


Assessing Facilitators and Barriers to Referral of Children Under the Age of Five Years at Ndirande Health Centre in Blantyre, Malawi.

Abstract: Patient referrals among health facilities are initiated to maximize receipt of quality care at a proper level within the health system. This study explored the processes, factors that influence, and strategies for referral of children from Ndirande Health Centre to Queen Elizabeth Central Hospital in Blantyre, Malawi. We drew a purposive sample comprising health care workers, mothers, fathers, ambulance drivers, and Health Center Advisory Committee (HCAC) members and held 19 in-depth interviews and 1 focus group discussion in August 2020. The referral process is influenced by the availability of motor and bicycle ambulances that are well equipped with medical equipment, delay in seeking health services, uptake of referral, and community support. Education and communication with the community and parents respectively optimize the process of referral. There is a need to improve the referral system of under-five children by instituting a policy that is functional while addressing the main barriers.

Referrals
Children
Ambulances
referral system


Role of lipolysis in postoral and oral fat preferences in mice.

Abstract: Fatty acid receptors in the mouth and gut are implicated in the appetite for fat-rich foods. The role of lipolysis in oral- and postoral-based fat preferences of C57BL/6J mice was investigated by inhibiting lipase enzymes with orlistat. Experiment 1 showed that postoral lipolysis is required: mice learned to prefer (by 70%) a flavored solution paired with intragastric infusions of 5% soybean oil but not a flavor paired with soybean oil + orlistat (4 mg/g fat) infusions. Experiments 2-4 tested the oral attraction to oil in mice given brief choice tests that minimize postoral effects. In experiment 2, the same low orlistat dose did not reduce the strong (83-94%) preference for 2.5 or 5% soybean oil relative to fat-free vehicle in 3-min tests. Mice in experiment 3 given choice tests between two fat emulsions (2% triolein, corn oil, or soybean oil) with or without orlistat at a high dose (250 mg/g fat) preferred triolein (72%) and soybean oil (67%) without orlistat to the oil with orlistat but were indifferent to corn oil with and without orlistat. In experiment 4, mice preferred 2% triolein (62%) or soybean oil (89%) to vehicle when both choices contained orlistat (250 mg/g fat). Fatty acid receptors are thus essential for postoral but not oral-based preferences. Both triglyceride and fatty acid taste receptors may mediate oral fat preferences.

orlistat
intragastric infusions
soybean oil
corn oil
triolein oil


Abnormal maternal echocardiographic findings in triplet pregnancies presenting with dyspnoea.

Abstract:
OBJECTIVE
The objective of our study was to evaluate the prevalence of abnormal maternal echocardiographic findings in triplet pregnancies presenting with dyspnoea.

STUDY DESIGN
Between 2003 and 2013, patients' records of 96 triplet pregnancies at our department were analysed including maternal and fetal outcome, echocardiographic parameters and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. After exclusion of triplet pregnancies with fetal demise before 23 + 0 weeks, selective feticide or missing outcome data, the study population consisted of 60 triplet pregnancies. All women with dyspnoea underwent echocardiography and measurement of NT-proBNP.

RESULTS
Dyspnoea towards the end of pregnancy was observed in 13.3% (8/60) of all women with triplet pregnancies, and all of these women underwent echocardiography. The prevalence of abnormal echocardiographic findings in women with dyspnoea was 37.5% (3/8) with peripartum cardiomyopathy in one woman. Median serum NT-proBNP was significantly higher in women with abnormal echocardiographic findings compared with those without (1779 ng/ml, range 1045-6076 ng/ml vs 172 ng/ml, range 50-311 ng/ml; p < 0.001 by Mann-Whitney-U Test).

CONCLUSION
We conclude that triplet pregnancies presenting with dyspnoea show a high prevalence of abnormal echocardiographic findings. Since dyspnoea is a common sign in triplet pregnancies and is associated with a high rate of cardiac involvement, echocardiography and evaluation of maternal NT-proBNP could be considered to improve early diagnosis and perinatal management.

Elhenicky|Marie|M| Distelmaier|Klaus|K| Mailath-Pokorny|Mariella|M| Worda|Christof|C| Langer|Martin|M| Worda|Katharina|K|

Triplet pregnancy
Pro-B-type natriuretic peptide
Dyspnoea in pregnancy
Maternal echocardiography
Multiple pregnancy


Mental health issues among college students: who gets referred for psychopharmacology evaluation?

Abstract:
OBJECTIVE
To describe diagnostic and psychotropic medication prescription characteristics among college students referred by college counseling centers for psychopharmacologic evaluation.

PARTICIPANTS
Participants were 540 college students referred by 6 college counseling centers in Massachusetts between November 2005 and May 2011.

METHODS
Students completed self-report measures of depression, anxiety, suicidal ideation and attempts, and substance use. Information regarding DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th edition) diagnosis, previous history of medication prescription, and current psychotropic medication(s) prescribed by the consulting psychiatrist was obtained from medical records.

RESULTS
Depression, anxiety, and attention-deficit/hyperactivity disorder (ADHD) were the most common psychiatric problems identified in students. Half of these students had been prescribed mediation prior to evaluation. Antidepressant medication was the most frequently prescribed medication. A large proportion of students reported previous thoughts of suicide, and 12% had made at least 1 suicide attempt.

CONCLUSIONS
Depression, anxiety, and ADHD are common among students referred by college counseling centers for medication evaluation and treatment.

Kirsch|Daniel J|DJ|
Doerfler|Leonard A|LA|
Truong|Debbie|D|


Sesquiterpenoids from the root of Panax Ginseng protect CCl4-induced acute liver injury by anti-inflammatory and anti-oxidative capabilities in mice.

Abstract: The oxidative stress and inflammatory response play an important role in carbon tetracholoride (CCl4)-induced acute liver injury. In this work, sesquiterpenoids from the root of Panax Ginseng (SPG) were prepared, and then the hepatoprotective effects of SPG against CCl4-induced acute liver injury were investigated and the underlying mechanism was explored in mice. All mice were divided into four groups: the control, CCl4 and SPG (2.5 and 10 mg/kg, dissolved in soybean oil, i.g.) groups. All mice were given continuous administration for 7 days, and injected with CCl4 (0.1 mL/10 g body weight 0.2% CCl4 solution in soybean oil, i.p.) 1 h after the end of the administration except the control group. Mice were sacrificed 24 h post-CCl4 injection. The results indicated that SPG significantly reduced the increasement of serum AST and ALT levels induced by CCl4-treatment. And the histopathological analysis revealed that SPG treated mice had normal liver architecture and no necrosis. The decreased activities of SOD, GSH and CAT, and increased MDA level were inhibited by SPG treatment. At the same time, the levels of TNF-α, IL-1β and IL-6 were significantly decreased by SPG treatment. SPG treatment also reduced the heptic protein expressions of NF-κB p65, COX-2, MAPK p38, ERK and JNK in the liver. These fingdings demonstrated that SPG exhibited strong hepatoprective effect on the CCl4-induced acute liver injury, which was related to anti-oxidantive and anti-inflammatory capabilities; and the anti-inflammatory effect of SPG might mediated by the NF-κB and MAPKs signaling pathways. Taken together, SPG might be a potential material for drug and functional food development against chemical hepatic injury.

Wang|Weidong|W| Wang|Shijie|S| Liu|Jinping|J| Cai|Enbo|E| Zhu|Hongyan|H| He|Zhongmei|Z| Gao|Yugang|Y| Li|Pingya|P| Zhao|Yan|Y|

Sesquiterpenoids
Acute liver injury
Anti-inflammatory
Anti-oxidative
Carbon tetrachloride


Morphologic Change of Parvalbumin-positive Myelinated Axons in the Human Dental Pulp.

Abstract:
INTRODUCTION
Information on the nerve fibers innervating the dental pulp is crucial for understanding dental pain and hypersensitivity. This study investigated the morphologic differences of parvalbumin (PV)-positive (+) myelinated fibers in 3 different regions of the human dental pulp.

METHODS
Light and electron microscopic immunohistochemistry for parvalbumin, a marker for myelinated fibers, and quantitative analysis were performed in the apical root, core of coronal pulp, and peripheral pulp of human premolar teeth.

RESULTS
About 40% of the myelinated fibers in the apical root pulp became unmyelinated in the core of the coronal pulp, and virtually all the remaining fibers became unmyelinated at the peripheral pulp. The size of myelinated axons decreased from root to peripheral pulp. PV+ axons showed extensive axonal varicosities in the peripheral pulp.

CONCLUSIONS
These findings suggest that the myelinated fibers innervating the human dental pulp undergo extensive morphologic change in the extrapulpal region and in the coronal and peripheral pulp, and that PV-mediated regulation of calcium concentration and its downstream events may occur primarily in axonal varicosities in the peripheral pulp.

Kim|Tae Heon|TH|
Park|Sook Kyung|SK|
Choi|So Young|SY|
Lee|Jae Sik|JS|
Bae|Yong Chul|YC|

myelinated axon
Dental pulp
parvalbumin
ultrastructure


Seroepidemiology of Hepatitis Viruses and Hepatitis B Genotypes of Female Marriage Immigrants in Korea.

Abstract:
PURPOSE
The Korean society has moved rapidly toward becoming a multicultural society. This study aimed to estimate the seroprevalence of hepatitis viruses and investigate hepatitis B virus (HBV) genotypic diversity in female marriage immigrants.

MATERIALS AND METHODS
Screening program was conducted at support centers for multicultural families in 21 administrative districts in Korea between July 2011 and January 2017. A total of 963 female marriage immigrants were included in this study. Blood samples were tested for hepatitis viral markers and HBV genotype.

RESULTS
Subjects' median age was 33 years (20-40 years), and they originated from nine countries including Vietnam (n=422, 43.8%), China (n=311, 32.3%), the Philippines (n=85, 8.8%), Cambodia (n=58, 6.0%), and Japan (n=39, 4.0%). About 30% (n=288) of subjects required hepatitis A vaccination. HBsAg positive rate was 5.4% (n=52). Positive HBsAg results were the highest in subjects from Southeast Asia (6.6%, n=38). Anti-HBs positive rate was 60.4% (n=582). About 34% (n=329) of subjects who were negative for anti-HBs and HBsAg required HBV vaccinations. Genotypes B and C were found in 54.6% (n=12) and 45.4% (n=10) of the 22 subjects with HBV, in whom genotypes were tested. Eight (0.8%) subjects were positive for anti-HCV. Positive anti-HCV results were the highest in subjects from Central Asia (7.9%, n=3).

CONCLUSION
Testing for hepatitis viral marker (hepatitis A virus IgG and HBsAg/anti-HBs) is needed for female marriage immigrants. Especially, HBV genotype B is different from genotype C of Koreans. Therefore, interest and attention to vaccination programs for female marriage immigrants are necessary for both clinicians and public health institutes.

genotype
marriage
immigrants
Hepatitis virus
prevalence


Relationships among Lifestyle Awareness, Age, and Lifestyle-related Diseases in Healthy Japanese Community Residents.

Abstract: Purpose: It is widely known that the risk of lifestyle-related diseases can be reduced by reviewing lifestyles, and a variety of efforts for their prevention, such as health education, are being implemented. This study examined community residents' lifestyle awareness, examining their views on their health and lifestyles, age, and lifestyle-related diseases. Methods: Study subjects were 180 healthy people (28 men and 152 women) who participated in a health checkup. Participants answered a questionnaire about their awareness of health and lifestyle and their views of disorders. Subsequent measurements of speed of sound (SOS), acceleration plethysmography (APG), and visceral fat area (VFA) were also obtained. Results: The results of the study suggest that age was correlated with some health-related attitudes and behaviors. When health awareness among members of a group is high, it is necessary to provide them with the required information and continuing intervention to motivate them to continue their health improvement. Conclusion: It seems that health awareness influences lifestyle, and its improvement slows the progress of lifestyle-related diseases and reduces the effects of aging.

lifestyle
health awareness
attitude to health
health behavior
health promotion


Feasibility of Virtual Reality Audiological Testing: Prospective Study.

Abstract:
BACKGROUND
It has been noted in the literature that there is a gap between clinical assessment and real-world performance. Real-world conversations entail visual and audio information, yet there are not any audiological assessment tools that include visual information. Virtual reality (VR) technology has been applied to various areas, including audiology. However, the use of VR in speech-in-noise perception has not yet been investigated.

OBJECTIVE
The purpose of this study was to investigate the impact of virtual space (VS) on speech performance and its feasibility to be used as a speech test instrument. We hypothesized that individuals' ability to recognize speech would improve when visual cues were provided.

METHODS
A total of 30 individuals with normal hearing and 25 individuals with hearing loss completed pure-tone audiometry and the Korean version of the Hearing in Noise Test (K-HINT) under three conditions-conventional K-HINT (cK-HINT), VS on PC (VSPC), and VS head-mounted display (VSHMD)-at -10 dB, -5 dB, 0 dB, and +5 dB signal-to-noise ratios (SNRs). Participants listened to target speech and repeated it back to the tester for all conditions. Hearing aid users in the hearing loss group completed testing under unaided and aided conditions. A questionnaire was administered after testing to gather subjective opinions on the headset, the VSHMD condition, and test preference.

RESULTS
Provision of visual information had a significant impact on speech performance between the normal hearing and hearing impaired groups. The Mann-Whitney U test showed statistical significance (P<.05) between the two groups under all test conditions. Hearing aid use led to better integration of audio and visual cues. Statistical significance through the Mann-Whitney U test was observed for -5 dB (P=.04) and 0 dB (P=.02) SNRs under the cK-HINT condition, as well as for -10 dB (P=.007) and 0 dB (P=.04) SNRs under the VSPC condition, between hearing aid and non-hearing aid users. Participants reported positive responses across almost all items on the questionnaire except for the weight of the headset. Participants preferred a test method with visual imagery, but found the headset to be heavy.

CONCLUSIONS
Findings are in line with previous literature that showed that visual cues were beneficial for communication. This is the first study to include hearing aid users with a more naturalistic stimulus and a relatively simple test environment, suggesting the feasibility of VR audiological testing in clinical practice.

virtual reality
audiology
real-world performance
speech performance
hearing
hearing loss


Radiofrequency ablation combined with chemolipiodolization in a porcine liver: Comparison of the pharmacokinetic analysis with cisplatin powder and miriplatin.

Abstract:
AIM
To compare the pharmacokinetics of radiofrequency (RF) ablation with chemolipiodolization using cisplatin (CDDP) powder and miriplatin (MPT) in a porcine liver.

METHODS
Twelve pigs were divided equally into four groups. After each CDDP powder-lipiodol suspension (n = 6; groups A and B) or MPT-lipiodol suspension (n = 6; groups C and D) was injected into the lateral left artery, one RF ablation was performed at the lateral left lobe of each pig. Six pigs (groups A and C) were killed on the same day as treatment, whereas the other pigs (groups B and D) were killed 7 days after the treatment. The platinum concentrations in venous blood were assayed at 15, 60 and 120 min, and 7 days after treatment. The platinum concentrations in the ablated area and the surrounding liver were also examined.

RESULTS
Plasma platinum concentrations of the CDDP group peaked at 15 min, and then gradually diminished over time (μg units), while plasma platinum levels in the MPT group gradually increased over time (ng units). Liver tissue platinum concentrations of the CDDP group were significantly lower in non-ablative areas than in ablated areas at days 0 and 7, while liver concentrations of the MPT group were significantly higher in non-ablative areas than in ablated areas at day 7.

CONCLUSION
MPT may be a suitable chemotherapeutic agent to stagnate platinum in the surrounding liver.

Ito|Tomoyasu|T| Okubo|Hironao|H| Kokubu|Shigehiro|S| Miyazaki|Akihisa|A| Ando|Hitoshi|H| Fujimura|Akio|A| Watanabe|Sumio|S|

radiofrequency ablation
chemolipiodolization
pharmacokinetics
cisplatin
miriplatin
hepatocellular carcinoma


Imaging of growth factors on a human tooth root canal by surface-enhanced Raman spectroscopy.

Abstract: Endodontic treatment of immature permanent teeth with necrotic pulp poses several clinical challenges and is one of the most demanding interventions in endodontics. Recently, with new discoveries in the field of tissue engineering, novel treatment protocols have been established. The most promising treatment modality is revascularization, whose integral part is the exposure of collagen matrix and embedded growth factors. However, optimization of the treatment protocol requires a development of analytical procedures able to analyze growth factors directly on the sample surface. In this work, method based on surface-enhanced Raman spectroscopy (SERS) was developed to investigate the influence of the time of the medical treatment using EDTA on exposure and accessibility of the growth factors, namely TGF-ß1, BMP-2, and bFGF on the dentine surface. The nanotags, which consist of magnetic Fe3O4@Ag nanocomposite covalently functionalized by tagged antibodies (anti-TGF-ß1-Cy3, anti-BMP-2-Cy5, and anti-bFGF-Cy7), were employed as a SERS substrate. Each antibody was coupled with a unique label allowing us to perform a parallel analysis of all three growth factors within one analytical run. Developed methodology presents an interesting alternative to a fluorescence microscopy and in contrary allows evaluating a chemical composition and thus minimizing possible false-positive results. Graphical abstract.

Imaging
Growth factors
SERS
Nanocomposites


Surgical Repair of Congenital Atresia of the Left Coronary Ostium.

Abstract: Congenital left main coronary artery atresia is an exceedingly rare condition with potentially fatal consequences if not diagnosed in a timely fashion. We present a case series in children and adolescents, including surgical repair and outcomes. We describe the presenting symptoms and subsequent management of each patient, including surgical repair and outcomes. (Level of Difficulty: Advanced.).

Hartz|Jacob|J|
Nathan|Meena|M|
Newburger|Jane W|JW|
Quinonez|Luis|L|

CLMCAA, congenital left main coronary artery atresia

cCTA, cardiac computed tomography angiography


Umbilical cord blood cells regulate the differentiation of endogenous neural stem cells in hypoxic ischemic neonatal rats via the hedgehog signaling pathway.

Abstract: Transplantation of umbilical cord blood mononuclear cells (UCBMC) promotes the proliferation of endogenous neural stem cells (NSCs), but it has been unclear whether the proliferating NSCs can differentiate into mature neural cells. Therefore, we explored the effects of UCBMC transplantation on the differentiation of endogenous NSCs and their underlying mechanisms. Seven-day-old Sprague-Dawley rats underwent left carotid ligation followed by hypoxic stress. UCBMC were transplanted 24h after hypoxia ischemia (HI). BrdU/β-tubulin/HNA/DAPI, BrdU/GFAP/HNA/DAPI, Ngn1/DAPI, and BMP4/DAPI were measured by immunofluorescence staining; Shh, Gli1, Ngn1, and BMP4 proteins were measured by western-blot analysis 28 days after transplantation. More newborn neurons and fewer astrocytes were observed in the HI+UCBMC group, its neuronal percentage was higher, and glial percentage was lower compared with the N+UCBMC (P<0.05) and HI+PBS groups (P<0.01), while fewer newborn neurons and more newborn astrocytes were found in the HI+cyclopamine (an antagonist of the hedgehog protein)+UCBMC group compared with the HI+UCBMC group (P<0.01). The expression of Shh, Gli1, and Ngn1 proteins was higher and BMP4 protein was lower in the HI+UCBMC compared with the HI+PBS group (P<0.01) and the HI+cyclopamine+UCBMC group (P<0.01). Linear regression analysis showed that the differentiation of NSCs correlated with expression of Ngn1 and BMP4 proteins (P<0.01). In conclusion, UCBMC promote neuronal differentiation and reduce glial differentiation in hypoxic ischemic neonatal rats via the hedgehog signaling pathway.

D051792:Basic Helix-Loop-Helix Transcription Factors

D036101:Cord Blood Stem Cell Transplantation

Differentiation
Neural stem cell
Hedgehog
Umbilical cord blood mononuclear cells
HIBD


Adjuvant radiation with hormonal therapy is associated with improved survival in men with pathologically involved lymph nodes after radical surgery for prostate cancer.

Abstract:
PURPOSE
Recent studies have suggested that the addition of adjuvant radiation therapy (aRT) may improve outcomes in men with pathologically involved lymph nodes (pN+). The objective of this study was to assess the treatment patterns and the overall survival (OS) outcomes in men with pN+prostate cancer using the National Cancer Data Base.

METHODS
Men diagnosed with nonmetastatic prostate cancer between 2004 and 2011, who underwent radical prostatectomy for pN+were identified in the National Cancer Data Base. Patients were stratified into subgroups of those receiving no adjuvant therapy and those receiving adjuvant hormonal therapy (aHT) alone, aRT alone, and aRT+aHT. OS was analyzed using Kaplan-Meier method and compared between the groups using the log-rank test. Multivariable Cox regression was used to identify covariates that affected OS.

RESULTS
A total of 7,225 patients were included in this analysis, of whom 3,636 (50.3%) received no adjuvant therapy, 2,041 (28.2%) received aHT alone, 350 (4.8%) received aRT alone, and 1,198 (16.5%) received aRT+aHT. The 5-year OS rates were 85.2% for no adjuvant therapy, 82.9% for aHT alone, 88.3% for aRT alone, and 88.8% for combination hormonal therapy, i.e., aRT+aHT (P<0.001). On multivariable analysis, aRT+aHT was associated with a significantly decreased risk of death (hazard ratio [HR] = 0.67; 95% CI: 0.54-0.83; P<0.001) compared with no adjuvant therapy, whereas aHT alone (HR = 0.99; 95% CI: 0.85-1.15; P = 0.90) and aRT alone (HR = 1.02; 95% CI: 0.74-1.40; P = 0.92) were not.

CONCLUSION
Patients treated with multimodal aRT+aHT had significantly higher OS rate than patients treated without adjuvant therapy or with aHT/aRT alone.

Wong|Andrew T|AT|
Schwartz|David|D|
Osborn|Virginia|V|
Safdieh|Joseph|J|
Weiner|Joseph|J|
Schreiber|David|D|

D000230:Adenocarcinoma
D000368:Aged
D000369:Aged, 80 and over
D018931:Antineoplastic Agents, Hormonal
D017024:Chemotherapy, Adjuvant
D003131:Combined Modality Therapy
D006801:Humans
D053208:Kaplan-Meier Estimate
D008197:Lymph Node Excision
D008207:Lymphatic Metastasis
D008297:Male
D008875:Middle Aged
D060787:Neoplasm Grading
D011468:Prostatectomy
D011471:Prostatic Neoplasms
D018714:Radiotherapy, Adjuvant
D015996:Survival Rate

Prostate cancer
Outcomes
Prostatectomy
Combined modality therapy
Radiotherapy


Bacsnp: Using Single Nucleotide Polymorphism (SNP) Specificities and Frequencies to Identify Genotype Composition in Baculoviruses.

Abstract: Natural isolates of baculoviruses (as well as other dsDNA viruses) generally consist of homogenous or heterogenous populations of genotypes. The number and positions of single nucleotide polymorphisms (SNPs) from sequencing data are often used as suitable markers to study their genotypic composition. Identifying and assigning the specificities and frequencies of SNPs from high-throughput genome sequencing data can be very challenging, especially when comparing between several sequenced isolates or samples. In this study, the new tool "bacsnp", written in R programming langue, was developed as a downstream process, enabling the detection of SNP specificities across several virus isolates. The basis of this analysis is the use of a common, closely related reference to which the sequencing reads of an isolate are mapped. Thereby, the specificities of SNPs are linked and their frequencies can be used to analyze the genetic composition across the sequenced isolate. Here, the downstream process and analysis of detected SNP positions is demonstrated on the example of three baculovirus isolates showing the fast and reliable detection of a mixed sequenced sample.

dsDNA viruses
genome sequencing
Baculoviridae
Cydia pomonella granulovirus
genetic variability
sequence heterogeneity


The kappa opioid receptor modulates GABA neuron excitability and synaptic transmission in midbrainprojections from the insular cortex.

Abstract: As an integrative hub, the insular cortex (IC) translates external cues into interoceptive states that generate complex physiological, affective, and behavioral responses. However, the precise circuit and signaling mechanisms in the IC that modulate these processes are unknown. Here, we describe a midbrain-projecting microcircuit in the medial aspect of the agranular IC that signals through the Gαi/o-coupled kappa opioid receptor (KOR) and its endogenous ligand dynorphin (Dyn). Within this microcircuit, Dyn is robustly expressed in layer 2/3, while KOR is localized to deep layer 5, which sends a long-range projection to the substantia nigra (SN). Using ex vivo electrophysiology, we evaluated the functional impact of KOR signaling in layer 5 of the IC. We found that bath application of dynorphin decreased GABA release and increased glutamate release on IC-SN neurons, but did not alter their excitability. Conversely, dynorphin decreased the excitability of GABA neurons without altering synaptic transmission. Pretreatment with the KOR antagonist nor-BNI blocked the effects of dynorphin in IC-SN neurons and GABA neurons, indicating that the changes in synaptic transmission and excitability were selectively mediated through KOR. Selective inhibition of IC GABA neurons using a KOR-derived DREADD recapitulated these effects. This work provides insight into IC microcircuitry and indicates that Dyn/KOR signaling may act to directly reduce activity of layer 5 GABA neurons. In turn, KOR-driven inhibition of GABA promotes disinhibition of IC-SN neurons, which can modulate downstream circuits. Our findings present a potential mechanism whereby chronic upregulation of IC Dyn/KOR signaling can lead to altered subcortical function and downstream activity.

Pina|Melanie M|MM|
Pati|Dipanwita|D|
Hwa|Lara S|LS|
Wu|Sarah Y|SY|
Mahoney|Alexandra A|AA|
Omenyi|Chiazam G|CG|
Navarro|Montserrat|M|
Kash|Thomas L|TL|

Insular cortex
KOR
Dynorphin
Electrophysiology
Insula
KOR DREADD
KORD
Kappa-opioid receptor
Salvinorin B


Semi-automated estimation of left ventricular ejection fraction by two-dimensional and three-dimensional echocardiography is feasible, time-efficient, and reproducible.

Abstract:
PURPOSE
To compare two-dimensional (2D) and three-dimensional (3D) methods to estimate left ventricular ejection fraction (LVEF) with respect to feasibility, time consumption, and retest reproducibility.

METHODS
A total of 100 patients planned to undergo coronary artery bypass grafting and/or aortic valve replacement were included consecutively. 2D and 3D echocardiography was performed on all patients. Acquisition and analysis time as well as intra- and inter-examiner variability were assessed in 50 consecutive patients with 3 repeated echocardiographic examinations and analyses. LVEF was estimated by five different methods: uniplane, biplane, and single-beat triplane (SB3P), as well as semi-automated biplane (AutoEF) and 3D volumetric tracings (4D Auto LVQ). All methods were compared to Simpson's biplane method and feasibility was determined.

RESULTS
Feasibility of Simpson's uniplane method, Simpson's biplane method, AutoEF, SB3P, and 4D Auto LVQ was 97%, 92%, 86%, 70%, and 89%, respectively. All methods evaluated were 18%-33% faster (P < 0.001) than Simpson's biplane method (115 seconds, standard deviation 15 seconds). Compared to Simpson's biplane method mean LVEF was slightly underestimated by 4D Auto LVQ (-2 ± 8%, P = 0.02), but not significantly different when assessed by the other methods. AutoEF and 4D Auto LVQ showed the lowest test variability (intra-examiner coefficient of variation (CV) 10%-11%; inter-examiner CV 10%-12% vs intra-examiner CV 12%-18%; inter-examiner CV 12%-20%).

CONCLUSIONS
Estimation of LVEF by modern semi-automated 2D and 3D echocardiographic modalities is feasible, time-efficient, and reproducible.

Myhr|Katrine A|KA|0000-0003-0838-0987
Pedersen|Frederik H G|FHG|
Kristensen|Charlotte B|CB|
Visby|Lasse|L|
Hassager|Christian|C|
Mogelvang|Rasmus|R|

left ventricular ejection fraction
three-dimensional echocardiography
cardiac imaging


Transcatheter occlusion of the patent ductus arteriosus in premature infants weighing less than 1200 g.

Abstract:
OBJECTIVES
Over the last few decades different strategies have been proposed to treat persistent ductal patency in premature infants. The advent of the Amplatzer Duct Occluder II Additional Size (ADOIIAS) provided the potential to close the patent ductus arteriosus (PDA). Opinions differ on the significance and treatment of PDA in premature neonates. Because surgical ligation and medical therapy both have their drawbacks, interventional catheterisation can be considered as an alternative means of closing the ductus arteriosus. Our aim was to analyse the feasibility, safety and efficacy of this device in premature infants weighing <1200 g at procedure.

METHODS
Eighteen premature infants underwent transcatheter closure. The procedure was performed in the catheterisation laboratory by venous cannulation without angiography. The position of the occluder was directed by X-ray and ultrasound. We looked at procedural details, device size selection, complications and short-term and mid-term outcomes.

RESULTS
Eighteen infants born at gestational ages ranging between 23.6 and 29+6 weeks (mean±SD 25+6±3 weeks) underwent transcatheter PDA closure. Their mean age and weight at the time of the procedure was 20 days (range 8-44 days) and 980 g (range 680-1200 g), respectively. The mean PDA and device waist diameters were 3.2±0.6 mm (range 2.2-4 mm) and 4.5±0.6 mm, respectively, and the mean PDA and device lengths were 4.3±1.2 mm (range 2-10 mm) and 2.5±0.9 mm, respectively. Complete closure was achieved in all but one patient. There was no device migration. One patient developed a left pulmonary artery obstruction. Three infants died. Two deaths were related to complications of prematurity and one to the procedure.

CONCLUSIONS
Transcatheter closure of a PDA is feasible in very low weight infants with ADOIIAS and is an alternative to surgery. Success requires perfect selection and placement of the occluder.

Morville|Patrice|P| Douchin|Stephanie|S| Bouvaist|Helene|H| Dauphin|Claire|C|

D006328:Cardiac Catheterization
D004374:Ductus Arteriosus, Patent
D006801:Humans
D007223:Infant
D007230:Infant, Low Birth Weight
D007231:Infant, Newborn
D007234:Infant, Premature
D055989:Septal Occluder Device
D016896:Treatment Outcome

patent ductus arteriosus preterm infants

treatment of patent ductus arteriosus in preterm infants


'You can't say, "what about me?" I'm not the one with cancer': information and support needs of relatives.

Abstract:
OBJECTIVE
The aims of this study were to explore relatives' experiences of talking about cancer within the family and to identify their information and support needs.

METHOD
A cross-sectional in-depth interview study with relatives and partners (n = 22) of cancer patients recruited through community settings was conducted. A thematic approach was used for analysis.

RESULTS
Information sharing and communication within families operated within a context of cancer-related uncertainty. Discussion about cancer was generally viewed as beneficial, but relatives faced dilemmas, which inhibited information exchange. Participants often devised strategies to manage the challenges faced to fulfil their needs for information and support. This was deemed important as talking about cancer allowed relatives to support patients' preferences for care, deal with practical demands and come to terms with difficult issues. Lack of information was perceived to affect the quality of care participants could provide.

CONCLUSION
Participants did not always want to know everything about the patient's illness, suggesting the importance of tailoring information to individual needs. Offering a range of different kinds of support directly to relatives may improve patient care and emotional well-being.

Foster|Claire|C| Myall|Michelle|M| Scott|Isobel|I| Sayers|Mary|M| Brindle|Lucy|L| Cotterell|Phil|P| Addington-Hall|Julia|J| Hopkinson|Jane|J| Payne|Sheila|S| Robinson|Judith|J|

cancer
support
information sharing
information needs
oncology
relatives of cancer patients


A Diffusive Sveir Epidemic Model with Time Delay and General Incidence.

Abstract:
In this paper, we consider a delayed diffusive SVEIR model with general incidence. We first establish the threshold dynamics of this model. Using a Nonstandard Finite Difference (NSFD) scheme, we then give the discretization of the continuous model. Applying Lyapunov functions, global stability of the equilibria are established. Numerical simulations are presented to validate the obtained results. The prolonged time delay can lead to the elimination of the infectiousness.

Electronic Supplementary Material
Supplementary material is available in the online version of this article at 10.1007/s10473-021-0421-9.

Zhou|Jinling|J| Ma|Xinsheng|X| Yang|Yu|Y| Zhang|Tonghua|T|

SVEIR model
Lyapunov function
nonstandard finite difference method
vaccination


Tick-Bacteria Mutualism Depends on B Vitamin Synthesis Pathways.

Abstract: Mutualistic interactions with microbes have facilitated the radiation of major eukaryotic lineages [1, 2]. Microbes can notably provide biochemical abilities, allowing eukaryotes to adapt to novel habitats or to specialize on particular feeding niches [2-4]. To investigate the importance of mutualisms for the exclusive blood feeding habits of ticks, we focused on a bacterial genus of medical interest, Francisella, which is known to include both virulent intracellular pathogens of vertebrates [5, 6] and maternally inherited symbionts of ticks [7-9]. Through a series of physiological experiments, we identified a Francisella type, F-Om, as an obligate nutritional mutualist in the life cycle of the African soft tick Ornithodoros moubata. Francisella F-Om mutualism synthesizes B vitamins that are deficient in the blood meal of ticks. Indeed, experimental elimination of Francisella F-Om resulted in alteration of tick life history traits and physical abnormalities, deficiencies which were fully restored with an oral supplement of B vitamins. We also show that Francisella F-Om is maternally transmitted to all maturing tick oocytes, suggesting that this heritable symbiont is an essential adaptive element in the life cycle of O. moubata. The Francisella F-Om genome further revealed a recent origin from a Francisella pathogenic life style, as observed in other Francisella symbionts [6, 7, 10]. Though half of its protein-coding sequences are now pseudogenized or lost, Francisella F-Om has kept several B vitamin synthesis pathways intact, confirming the importance of these genes in evolution of its nutritional mutualism with ticks.

Duron|Olivier|O| Morel|Olivier|O| Noël|Valérie|V| Buysse|Marie|M| Binetruy|Florian|F| Lancelot|Renaud|R| Loire|Etienne|E| Ménard|Claudine|C| Bouchez|Olivier|O| Vavre|Fabrice|F| Vial|Laurence|L|

B vitamins
ticks
Francisella
hematophagy
symbiosis


Mepiquat chloride promotes cotton lateral root formation by modulating plant hormone homeostasis.

Abstract:
BACKGROUND
Mepiquat chloride (MC), a plant growth regulator, enhances root growth by promoting lateral root formation in cotton. However, the underlying molecular mechanisms of this phenomenon is still unknown.

METHODS
In this study, we used 10 cotton (Gossypium hirsutum Linn.) cultivars to perform a seed treatment with MC to investigate lateral root formation, and selected a MC sensitive cotton cultivar for dynamic monitor of root growth and transcriptome analysis during lateral root development upon MC seed treatment.

RESULTS
The results showed that MC treated seeds promotes the lateral root formation in a dosage-depended manner and the effective promotion region is within 5 cm from the base of primary root. MC treated seeds induce endogenous auxin level by altering gene expression of both gibberellin (GA) biosynthesis and signaling and abscisic acid (ABA) signaling. Meanwhile, MC treated seeds differentially express genes involved in indole acetic acid (IAA) synthesis and transport. Furthermore, MC-induced IAA regulates the expression of genes related to cell cycle and division for lateral root development.

CONCLUSIONS
Our data suggest that MC orchestrates GA and ABA metabolism and signaling, which further regulates auxin biosynthesis, transport, and signaling to promote the cell division responsible for lateral root formation.

Wu|Qian|Q| Du|Mingwei|M| Wu|Jie|J| Wang|Ning|N| Wang|Baomin|B| Li|Fangjun|F| Tian|Xiaoli|X| Li|Zhaohu|Z|

D018506:Gene Expression Regulation, Plant

Cotton
Lateral root
Mepiquat chloride (MC)
Transcriptome
Phytohormone


Multisectoral Actions for Health: Challenges and Opportunities in Complex Policy Environments.

Abstract: Multisectoral actions for health, defined as actions undertaken by non-health sectors to protect the health of the population, are essential in the context of inter-linkages between three dimensions of sustainable development: economic, social, and environmental. These multisectoral actions can address the social and economic factors that influence the health of a population at the local, national, and global levels. This editorial identifies the challenges, opportunities and capacity development for effective multisectoral actions for health in a complex policy environment. The root causes of the challenges lie in poor governance such as entrenched political and administrative corruption, widespread clientelism, lack of citizen voice, weak social capital, lack of trust and lack of respect for human rights. This is further complicated by the lack of government effectiveness caused by poor capacity for strong public financial management and low levels of transparency and accountability which leads to corruption. The absence of or rapid changes in government policies, and low salary in relation to living standards result in migration out of qualified staff. Tobacco, alcohol and sugary drink industries are major risk factors for non-communicable diseases (NCDs) and had interfered with health policy through regulatory capture and potential law suits against the government. Opportunities still exist. Some World Health Assembly (WHA) and United Nations General Assembly (UNGA) resolutions are both considered as external driving forces for intersectoral actions for health. In addition, Thailand National Health Assembly under the National Health Act is another tool providing opportunity to form trust among stakeholders from different sectors. Capacity development at individual, institutional and system level to generate evidence and ensure it is used by multisectoral agencies is as critical as strengthening the health literacy of people and the overall good governance of a country.

Tangcharoensathien|Viroj|V| Srisookwatana|Orapan|O| Pinprateep|Poldej|P| Posayanonda|Tipicha|T| Patcharanarumol|Walaiporn|W|

D014943:Global Health
D033161:Government Regulation
D006291:Health Policy
D006293:Health Promotion
D054625:Healthcare Disparities
D006801:Humans
D014480:United Nations

Multisectoral Action
Health
Challenge
Opportunity
Policy
Capacity


Psychometric properties of outcome measures in non-pharmacological interventions of persons with dementia in low-and middle-income countries: A systematic review.

Abstract: Despite high burden of dementia in low-and middle-income countries (LMICs), only a small number of clinical trials of psychosocial interventions for persons with dementia (PwD) have been conducted in these settings. It is essential that such trials use appropriate outcome measures that are methodologically robust and culturally appropriate to evaluate the effectiveness of interventions. We carried out a systematic review to examine the evidence base and psychometric properties of measures employed in these studies in LMICs. A systematic search of published literature on randomised controlled trials (RCT) of psychosocial interventions for PwD in LMICs between 2008 and April 2020 was carried out. Measures employed in each of the eligible studies were identified and through a focused search, we further explored the evidence base and psychometric properties employing Terwee criteria. Data extraction and quality appraisal were conducted by two independent reviewers. The review identified 41 measures from 17 RCTS which fulfilled eligibility criteria and they examined effectiveness across the domains of cognition (n = 16), behaviour and psychological symptoms (n = 11) and quality of life (n = 8). Of these 41, we were able to access relevant literature only for 18 and they were subject to psychometric analysis. Psychometric properties of these 18 instruments were at best modest, with Terwee scores ranging from 3 (low) to 15 (moderate). A majority of the studies were from China (n = 5) and Brazil (n = 6). The evidence base for the routinely employed measures in RCTs of non-pharmacological interventions for PwD in LMICs is limited. The quality of adaptation and validation of these instruments is variable and studies are largely uninformative about their psychometric properties and cultural appropriateness to the study setting. There is an urgent need to develop scientifically robust instruments in LMIC settings that can be confidently employed to measure outcomes in trials of psychosocial interventions for PwD.

psychometric properties
outcome measures
dementia
low middle income countries
non-pharmacological therapy


Granulomatous reaction to Belotero Balance: A case study.

Abstract:
OBJECTIVE
The most commonly used dermal fillers are hyaluronic acids (HAs), and in general, are well tolerated with mild to moderate risk of adverse events. The most frequently reported side effects are injection site erythema and bruising. We present the first case of a patient who developed a severe granulomatous foreign body reaction to the HA filler, Belotero Balance. In our review of the literature, a granulomatous reaction has never before been reported as a side effect of this particular HA filler (1).

CASE
On exam, the patient had firm erythematous, granulomatous plaques on her bilateral cheeks, with a tender, fluctuant nodule on her right cheek. Complete resolution of this delayed reaction was achieved after several injections of intralesional Kenalog (IL-K) 2.5 mg/cc, and further fine-tuning was achieved through laser resurfacing.

CONCLUSION
Granulomatous reactions can occur with any HAs, though such incidents are not commonly reported. These delayed reactions are generally localized immunological reactions, though biofilm infections should be excluded where appropriate. It is only with long-term (5-year) longitudinal studies that accurate numbers of such reactions will be known.

D000067548:Dermal Fillers
D005148:Facial Dermatoses
D005260:Female
D015745:Granuloma, Foreign-Body
D006801:Humans
D006820:Hyaluronic Acid
D008875:Middle Aged

granulomatous reaction
Belotero
filler
Granuloma


Trichormus variabilis (Cyanobacteria) Biomass: From the Nutraceutical Products to Novel EPS-Cell/Protein Carrier Systems.

Abstract: A native strain of the heterocytous cyanobacterium Trichormus variabilis VRUC 168 was mass cultivated in a low-cost photobioreactor for a combined production of Polyunsaturated Fatty Acids (PUFA) and Exopolymeric Substances (EPS) from the same cyanobacterial biomass. A sequential extraction protocol was optimized leading to high yields of Released EPS (REPS) and PUFA, useful for nutraceutical products and biomaterials. REPS were extracted and characterized by chemical staining, Reversed Phase-High-Performance Liquid Chromatography (RP-HPLC), Fourier Transform Infrared Spectroscopy (FT-IR) and other spectroscopic techniques. Due to their gelation property, REPS were used to produce a photo-polymerizable hybrid hydrogel (REPS-Hy) with addition of polyethylene glycol diacrylated (PEGDa). REPS-Hy was stable over time and resistant to dehydration and spontaneous hydrolysis. The rheological and functional properties of REPS-Hy were studied. The enzyme carrier ability of REPS-Hy was assessed using the detoxification enzyme thiosulfate:cyanide sulfur transferase (TST), suggesting the possibility to use REPS-Hy as an enzymatic hydrogel system. Finally, REPS-Hy was used as a scaffold for culturing human mesenchymal stem cells (hMSCs). The cell seeding onto the REPS-Hy and the cell embedding into 3D-REPS-Hy demonstrated a scaffolding property of REPS-Hy with non-cytotoxic effect, suggesting potential applications of cyanobacteria REPS for producing enzyme- and cell-carrier systems.

Bellini|Erika|E| Ciocci|Matteo|M| Savio|Saverio|S| Antonaroli|Simonetta|S| Seliktar|Dror|D| Melino|Sonia|S| Congestri|Roberta|R|

D017550:Spectroscopy, Fourier Transform Infrared

Trichormus variabilis
Cyanobacteria
PUFA
biomaterials
hydrogel
enzyme
mesenchymal stem cells
Extracellular Polymeric Substances
omega 3


Myxoid Adrenocortical Adenoma: A report of two cases and literature review.

Abstract: Myxoid adrenocortical adenomas are uncommon. There were only 61 cases reports documented, and the tumors are tended to be misdiagnosed in virtue of being rare and distinctive histological features. Recently we encountered two myxoid adrenocortical adenoma cases of a 31-year-old Chinese woman and a 45-year-old Chinese man. The patients did not receive further treatment after surgery and were still alive after following up for 20 months. Myxoid adrenocortical adenomas is extremely rare. Recognition of this entity would be beneficial for pathologists to avoid msidiagnosis, and unnecessary treatment.

Wu|Hongmei|H| Zhang|Fen|F| Chen|Yu|Y| Liu|Chao|C| Yao|Su|S| Zhu|Xiaolan|X| Luo|Xinlan|X| Zhuang|Hengguo|H| Liu|Yanhui|Y|


Novel two-step method to form silk fibroin fibrous hydrogel.

Abstract: Hydrogels prepared by silk fibroin solution have been studied. However, mimicking the nanofibrous structures of extracellular matrix for fabricating biomaterials remains a challenge. Here, a novel two-step method was applied to prepare fibrous hydrogels using regenerated silk fibroin solution containing nanofibrils in a range of tens to hundreds of nanometers. When the gelation process of silk solution occurred, it showed a top-down type gel within 30min. After gelation, silk fibroin fibrous hydrogels exhibited nanofiber network morphology with β-sheet structure. Moreover, the compressive stress and modulus of fibrous hydrogels were 31.9±2.6 and 2.8±0.8kPa, respectively, which was formed using 2.0wt.% concentration solutions. In addition, fibrous hydrogels supported BMSCs attachment and proliferation over 12days. This study provides important insight in the in vitro processing of silk fibroin into useful new materials.

Ming|Jinfa|J| Li|Mengmeng|M| Han|Yuhui|Y| Chen|Ying|Y| Li|Han|H| Zuo|Baoqi|B| Pan|Fukui|F|


Quality improvements to mackerel (Scomber japonicus) muscle tissue frozen using a rapid freezer with the weak oscillating magnetic fields.

Abstract: Although freezing is the most popular long-term food preservation method, the formation of ice crystals during the freezing process often degrades the quality of the product. Recently, several reports have argued that oscillating magnetic fields (OMFs) may affect ice crystallization. In this paper, we investigated the effects of OMFs on fresh mackerel using the Cell Alive System® (CAS®) developed as an additional OMF generator for a rapid freezer. Mackerel fillets were frozen with home freezing (HF), air blast freezing without (ABF) or with CAS (ABF-CAS) (ABI Co. Ltd., Chiba, Japan), and stored them for 2 weeks in the frozen storage between -30 °C and -35 °C. We analyzed the tissue damages of thawed samples histologically. The OMFs has been shown to significantly inhibit tissue damage in mackerel tissue after freezing and thawing (especially, thawing in ice water). And it seems that OMFs suppressed the ice hole counts (p < 0.05), the mean size (p = 0.061), and the increase of interstitial area% (p < 0.05) after freezing/thawing. We also found that it is necessary to avoid re-crystallization during thawing to maintain the quality of the frozen product. The use of OMFs with rapid thawing has the potential to improve cryopreservation in the food industry as well as in the bioscience industry.

Mackerel
Weak oscillating magnetic fields
Freezing
Cell Alive System® (CAS®)
Frozen storage
Thawing
Ice water
Air blast-freezer
Muscle fiber


Primary gross tumor volume is prognostic and suggests treatment in upper esophageal cancer.

Abstract:
BACKGROUND
To aid clinicians strategizing treatment for upper esophageal squamous cell carcinoma (ESCC), this retrospective study investigated associations between primary gross tumor volume (GTVp) and prognosis in patients given surgical resection, radiotherapy, or both resection and radiotherapy.

METHODS
The population comprised 568 patients with upper ESCC given definitive treatment, including 238, 216, and 114 who underwent surgery, radiotherapy, or combined radiotherapy and surgery. GTVp as a continuous variable was entered into the multivariate Cox model using penalized splines (P-splines) to determine the optimal cutoff value. Propensity score matching (PSM) was used to adjust imbalanced characteristics among the treatment groups.

RESULTS
P-spline regression revealed a dependence of patient outcomes on GTVp, with 30 cm3 being an optimal cut-off for differences in overall and progression-free survival (OS, PFS). GTVp ≥30 cm3 was a negative independent prognostic factor for OS and PFS. PSM analyses confirmed the prognostic value of GTVp. For GTVp < 30 cm3, no significant survival differences were observed among the 3 treatments. For GTVp ≥30 cm3, the worst 5-year OS rate was experienced by those given surgery. The 5-year PFS rate of patients given combined radiotherapy and surgery was significantly better than that of patients given radiotherapy. The surgical complications of patients given the combined treatment were comparable to those who received surgery, but radiation side effects were significantly lower.

CONCLUSION
GTVp is prognostic for OS and PFS in upper ESCC. For patients with GTVp ≥30 cm3, radiotherapy plus surgery was more effective than either treatment alone.

Chen|Yuanmei|Y| Huang|Qiuyuan|Q| Chen|Junqiang|J| Lin|Yu|Y| Huang|Xinyi|X| Wang|Qifeng|Q| Yang|Yong|Y| Chen|Bijuan|B| Ye|Yuling|Y| Zheng|Binglin|B| Qi|Rong|R| Chen|Yushan|Y| Xu|Yuanji|Y|


Recovery from respiratory failure after 49-day extracorporeal membrane oxygenation support in a critically ill patient with COVID-19: case report.

Abstract:
Background
Respiratory failure is a life-threatening complication of coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome. Extracorporeal membrane oxygenation (ECMO) in COVID-19 might offer promise based on our clinical experience. However, few critically ill cases with COVID-19 have been weaned off ECMO.

Case summary
A 66-year-old Chinese woman presented with fever (38.9°C), cough, dyspnoea, and headache. She had lymphopenia (0.72 × 109/L) and computed tomography findings of ground-glass opacities. Subsequently, she was confirmed to have respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. She was intubated after transfer to the intensive care unit due to respiratory failure and heart failure. However, her condition continued to deteriorate rapidly. Veno-veno ECMO was undertaken for respiratory and cardiac support due to refractory hypoxemic respiratory failure and bradyarrhythmia (45 b.p.m.). During hospitalization, she was also administered anti-viral treatment, convalescent plasma therapy, and continuous renal replacement therapy. She was maintained on ECMO before she had fully recovered from the condition that necessitated ECMO use and had a negative test for the nucleic acids of SARS-CoV-2 twice. Forty-nine days later, this patient was weaned from ECMO. At the most recent follow-up visit (3 months after weaning from ECMO), she received respiratory and cardiac rehabilitation and did not complain of any discomfort.

Discussion
As far as we know, the longest duration of ECMO treatment in this critical case with COVID-19 is supportive of ECMO as the most aggressive form of life support and the last line of defence during the COVID-19 epidemic.

Guo|Fengwei|F| Deng|Chao|C| Shi|Tao|T| Yan|Yang|Y|0000-0001-7167-0261

Extracorporeal membrane oxygenation
Case report
Coronavirus disease 2019
Acute respiratory distress syndrome


Association between interleukin-6/6R gene polymorphisms and coronary artery disease in Russian population: influence of interleukin-6/6R gene polymorphisms on inflammatory markers.

Abstract: This study determined the genotype effects of interleukin (IL)-6/IL-6R single nucleotide polymorphisms (SNPs) on circulating levels of different cytokines in healthy and coronary artery disease (CAD) patients with different allele frequencies. In the control patients, rs1800795 showed significant differences in IL-18 concentrations between CC and CG and CC and GG genotypes (P=0.003 and 0.004, respectively). Furthermore, circulatory IL-1β was significantly different between GC and GG genotypes from the same SNP (P=0.038). In the diseased patients, significance was determined only for IL-2 (P=0.021) between the C and G homozygote allele carriers of rs1800795. The diseased GC and GG genotype carriers were statistically different for IL-2 (P=0.049) from the rs1800796 and for IL-4 (P=0.049) from the rs2228044. IL-4 was also statistically significant between the GC and CC genotypes from the rs2228043 of the IL-6R gene (P=0.025). The last combination of genotypes in the same gene for the same SNP was statistically significant for IL-10 (P=0.036). According to the logistic regression, only gender (odds ratio [OR] =2.43) and triglycerides (OR =1.98) could be taken as determinants of CAD, while examined SNPs genotypes were not identified as risk factors for CAD. In general, the IL-6 polymorphism genotypes were mainly associated with inflammatory cytokines, while the IL-6R polymorphism genotypes were associated with anti-inflammatory cytokines.

Mitrokhin|Vadim|V| Nikitin|Alexey|A| Brovkina|Olga|O| Khodyrev|Dmitry|D| Zotov|Alexander|A| Vachrushev|Nikita|N| Dragunov|Dmitry|D| Shim|Andrey|A| Mladenov|Mitko|M| Kamkin|Andre|A|

coronary artery disease
cytokines
IL-6/IL-6R gene polymorphisms
inflammation


Appraisal of Non-Cardiovascular Safety for Sodium-Glucose Co-Transporter 2 Inhibitors: A Systematic Review and Meta-Analysis of Placebo-Controlled Randomized Clinical Trials.

Abstract: Background: Whereas the cardiovascular safety of sodium-glucose co-transporter 2 (SGLT2) inhibitors has been well reported, there is limited data from controlled clinical trials regarding the non-cardiovascular safety. This was the focus of our study. Methods and Findings: We systematically searched MEDLINE, EMBASE, and Cochrane Library (5th Sep 2018) for randomized controlled trials (RCTs) that reported safety data for SGLT2 inhibitors and placebo. Relative risks (RRs) and their 95% confidence intervals (CIs) were pooled using random-effects models. Seventy RCTs (83 studies enrolling 36,958 patients in 78 publications) were identified. SGLT2 inhibitors were associated with a lower risk of serious adverse events (RR 0.90, 95% CI 0.86 to 0.94, P < 0.001), death (RR 0.78, 95% CI 0.64 to 0.94, P < 0.05), gastroenteritis (RR 0.38, 95% CI 0.20 to 0.72, P < 0.05), arthralgia (RR 0.72, 95% CI 0.54 to 0.96, P < 0.05), hypertension (RR 0.61, 95% CI 0.50 to 0.75, P < 0.001), and edema/peripheral edema (RR 0.49, 95% CI 0.33 to 0.72, P < 0.001) compared to placebo. SGLT2 inhibitors were associated with higher risk of infections compared to placebo (RR 1.27, 95% CI 1.17 to 1.37, P < 0.001), especially for genital mycotic infection (GMI) (RR 3.71, 95% CI 3.19 to 4.32, P < 0.001). Other significant effects were observed for osmotic diuresis-related AEs (RR 2.73, 95% CI 2.20 to 3.40, P < 0.001), volume-related AEs (RR 1.26, 95% CI 1.08 to 1.46, P < 0.05), renal-related AEs (RR 1.36, 95% CI 1.02 to 1.80, P < 0.05), hypoglycemia (RR 1.18, 95% CI 1.10 to 1.26, P < 0.001), and increased blood ketone bodies (RR 2.00, 95% CI 1.01 to 3.97, P < 0.05). Subgroup and sensitivity analyses strengthened the robustness of primary results. Conclusion: Results from RCTs confirmed lower risk of death, serious adverse events, hypertension, and edema associated with type 2 diabetes mellitus (T2DM) patients treated with SGLT2 inhibitors when compared with placebo. The use of SGLT2 inhibitors were associated with higher risk of infection, osmotic diuresis, volume depletion effects, renal related AEs, and higher blood ketone bodies when compared with placebo.

Shi|Fang-Hong|FH| Li|Hao|H| Shen|Long|L| Zhang|Zhen|Z| Jiang|Yi-Hong|YH| Hu|Yao-Min|YM| Liu|Xiao-Yan|XY| Gu|Zhi-Chun|ZC| Ma|Jing|J| Lin|Hou-Wen|HW|

sodium-glucose co-transporter 2 inhibitors


Solventless Formation of G-Quartet Complexes Based on Alkali and Alkaline Earth Salts on Au(111).

Abstract: Template cations have been extensively employed in the formation, stabilization and regulation of structural polymorphism of G-quadruplex structures in vitro. However, the direct addition of salts onto solid surfaces, especially under ultra-high-vacuum (UHV) conditions, to explore the feasibility and universality of the formation of G-quartet complexes in a solventless environment has not been reported. By combining UHV-STM imaging and DFT calculations, we have shown that three different G-quartet-M (M: Na/K/Ca) complexes can be obtained on Au(111) using alkali and alkaline earth salts as reactants. We have also identified the driving forces (intra-quartet hydrogen bonding and electrostatic ionic bonding) for the formation of these complexes and quantified the interactions involved. Our results demonstrate a novel route to fabricate G-quartet-related complexes on solid surfaces, providing an alternative feasible way to bring metal elements to surfaces for constructing metal-organic systems.

Zhang|Chi|C| Wang|Likun|L| Xie|Lei|L| Kong|Huihui|H| Tan|Qinggang|Q| Cai|Liangliang|L| Sun|Qiang|Q| Xu|Wei|W|

D054856:G-Quadruplexes
D006046:Gold
D006860:Hydrogen Bonding
D008672:Metals, Alkali
D008673:Metals, Alkaline Earth
D016252:Microscopy, Scanning Tunneling
D011789:Quantum Theory
D013499:Surface Properties

G-quartet
salts
density functional theory
electrostatic ionic interactions
scanning tunneling microscopy