Evaluation of the 95% limits of agreement of the volumes of 5-year clinically stable solid nodules for the development of a follow-up system for indeterminate solid nodules in CT lung cancer screening.

Abstract:
Background
This study sought to evaluate the 95% limits of agreement of the volumes of 5-year clinically stable solid nodules for the development of a follow-up system for indeterminate solid nodules.

Methods
The volumes of 226 solid nodules that had been clinically stable for 5 years were measured in 186 patients (53 female never-smokers, 36 male never-smokers, 51 males with <30 pack-years, and 46 males with ≥30 pack-years) using a three-dimensional semiautomated method. Volume changes were evaluated using three methods: percent change, proportional change and growth rate. The 95% limits of agreement were evaluated using the Bland-Altman method.

Results
The 95% limits of agreement were as follows: range of percent change, from ±34.5% to ±37.8%; range of proportional change, from ±34.1% to ±36.8%; and range of growth rate, from ±39.2% to ±47.4%. Percent change-based, proportional change-based, and growth rate-based diagnoses of an increase or decrease in ten solid nodules were made at a mean of 302±402, 367±455, and 329±496 days, respectively, compared with a clinical diagnosis made at 809±616 days (P<0.05).

Conclusions
The 95% limits of agreement for volume change in 5-year stable solid nodules may enable the detection of an increase or decrease in the solid nodule at an earlier stage than that enabled by a clinical diagnosis, possibly contributing to the development of a follow-up system for reducing the number of additional Computed tomography (CT) scans performed during the follow-up period.

Kakinuma|Ryutaro|R| Muramatsu|Yukio|Y| Yamamichi|Junta|J| Gomi|Shiho|S| Oubel|Estanislao|E| Moriyama|Noriyuki|N|

follow-up
indeterminate solid nodule
lung cancer screening
Computed tomography (CT)
volumetry


Lycopene: redress for prostate cancer.

Abstract: Lycopene, a carotenoid is what that gives red colour to some fruits like pomegranate, tomato, papaya etc... People with a sound diet of lycopene may have a less risk of cancers especially prostate cancer which is most impedent for the males of age 40-50 years. So, in countries of north America and Europe food contains much of the lycopene supplements. In accordance with the American journal of epidemiology 2002 studies implies that men with crushed serum lycopene levels are more divulged to prostate cancer and those with sound diet of lycopene have a less risk of prostate cancer. In a care study conveyed by The British journal of urology, men with prostate cancer are subjected to surgery and the tumour is detonated. Amongst the men half a set were supplemented with lycopene supplements and half were not. Those subjected with lycopene supplements have less bone pains and live longer than those not supplemented. This paints a picture about importance of lycopene in treatment of prostate cancer. This article evokes the importance of lycopene and its way of destroying the cancer. Lycopene reduces the risk of cancer by diverging its effect on the plasma Insulin like growth factor, on Connexins , and the most acceptable one, by quench of free radicals.

Pisipati|Sai Venkata Vedavyas|SV|
Pathapati|Harshavardhan|H|
Bhukya|Ganesh|G|
Nuthakki|Suresh|S|
Chandu|Baburao|B|
Nama|SreeKanth|S|
Adeps|RajDev|R|

Lycopene
Prostate cancer
Insulin like growth factor
Connexins
Anti oxidant
conjugated bonds


Efficient conversion of Hubrid Pennisetum to glucose by oxygen-aqueous alkaline ionic liquid media pretreatment under benign conditions.

Abstract: To enhance the cellulose digestibility of energy grass hybrid Pennisetum (P. americanum×P. purpureum, HP) with low energy-consumption and high efficiency, a novel combinatorial pretreatment of oxygen-aqueous alkaline ionic liquid (IL) 1-ethyl-3-methylimidazolium acetate ([Emim]Ac) media (OEA) was developed in this work. The combinatorial pretreatment was performed under the relatively low temperature (120°C), short retention time (30min), and 12bar oxygen pressure. The combinatorial pretreatment of OEA was demonstrated effectively for pretreatment of hybrid Pennisetum, which evidenced by the removal of lignin, degradation of carbohydrate, and porosity property of the regenerated biomass. Subsequently, a higher glucose recovery (96.9%) at a low enzyme loading (20FPU/g substrate) was obtained by the OEA pretreatment, and it was 9.1 times as much as the untreated samples. Overall, the novel OEA combinatorial pretreatment has the advantages of low thermal energy input and enzyme usage, and short retention time.

Wang|Shengdan|S| Chen|Jiachuan|J| Yang|Guihua|G| Gao|Wenhua|W| Chen|Kefu|K|

Ionic liquid
Hybrid Pennisetum
Combined pretreatment
Enzymatic hydrolysis


Vaginal surgery: don't get bent out of shape.

Abstract: Vaginal hysterectomy rates in the United States are decreasing, despite it being the recommended hysterectomy route for benign hysterectomy by multiple societies. Visualization issues are a known barrier to a medical student learning in the operating room, and it is likely that this also extends to resident training. In addition, vaginal surgery can be taxing on both the surgeons and assistants, with high rates of musculoskeletal work disorders reported in vaginal surgeons. The use of a camera is integral to endoscopic surgery, and table-mounted retractor systems have been used for decades in open surgery. We bring these 2 features into vaginal surgery, that is, using a table-mounted camera system and a table-mounted vaginal retractor. When used together as demonstrated in this video, these tools can improve visualization and may improve ergonomics for the entire surgical team, including learners, during vaginal surgery.

Woodburn|Katherine L|KL|
Kho|Rosanne M|RM|

vaginal surgery
vaginal hysterectomy
ergonomics
surgical education


Hemagglutinin Nanoparticulate Vaccine with Controlled Photochemical Immunomodulation for Pathogenic Influenza-Specific Immunity.

Abstract: Recently, viral infectious diseases, including COVID-19 and Influenza, are the subjects of major concerns worldwide. One strategy for addressing these concerns focuses on nasal vaccines, which have great potential for achieving successful immunization via safe, easy, and affordable approaches. However, conventional nasal vaccines have major limitations resulting from fast removal when pass through nasal mucosa and mucociliary clearance hindering their effectiveness. Herein a nanoparticulate vaccine (NanoVac) exhibiting photochemical immunomodulation and constituting a new self-assembled immunization system of a photoactivatable polymeric adjuvant with influenza virus hemagglutinin for efficient nasal delivery and antigen-specific immunity against pathogenic influenza viruses is described. NanoVac increases the residence period of antigens and further enhances by spatiotemporal photochemical modulation in the nasal cavity. As a consequence, photochemical immunomodulation of NanoVacs successfully induces humoral and cellular immune responses followed by stimulation of mature dendritic cells, plasma cells, memory B cells, and CD4+ and CD8+ T cells, resulting in secretion of antigen-specific immunoglobulins, cytokines, and CD8+ T cells. Notably, challenge with influenza virus after nasal immunization with NanoVacs demonstrates robust prevention of viral infection. Thus, this newly designed vaccine system can serve as a promising strategy for developing vaccines that are active against current hazardous pathogen outbreaks and pandemics.

Jeong|Hayoon|H|
Lee|Chung-Sung|CS|
Lee|Jangsu|J|
Lee|Jonghwan|J|
Hwang|Hee Sook|HS|
Lee|Min|M|
Na|Kun|K|0000-0002-9629-0289

photochemical immunomodulation
nasal vaccine
influenza virus
nanovaccine
nasal antigen delivery


Comparison of Visual Field Measurement with Heidelberg Edge Perimeter and Humphrey Visual Field Analyzer in Patients with Ocular Hypertension.

Abstract:
BACKGROUND
Glaucoma is a group of eye diseases which result in damage to the optic nerve and vision loss. The most important examination in glaucoma patients is visual field assessment. One of the newer perimeters is Heidelberg Edge Perimeter (HEP).

OBJECTIVES
The aim of the study was to compare visual field measurements made with Humphrey II 740 Visual Field (Carl Zeiss Meditec) and Heidelberg Edge Perimeter (HEP) (Heidelberg Engineering). FDF stimulus (flicker defined form) in HEP stimulates magnocellular retinal cells, which are the first to be damaged in the early stage of glaucoma. Even a small loss of magnocellular cells may influence HEP visual field.

MATERIAL AND METHODS
The observed group consisted of 45 patients (82 eyes), age 60 ± 9.8 years, glaucoma suspects, not treated pharmacologically or surgically before, with intraocular pressure ≥ 22 mm Hg. Visual field values were measured with two different devices: Humphrey II 740 Visual Field (Carl Zeiss Meditec, Jena, Germany) and Heidelberg Edge Perimeter (Heidelberg Engineering, Heidelberg, Germany). The patients were divided into two groups: Group 1 - tested with SITA Standard program on Humphrey perimeter and ASTA Standard HEP, and Group 2 - tested with SITA Fast program on Humphrey perimeter and ASTA Standard on HEP.

RESULTS
Few positive ΔMD results (ΔMD = MD HEP - MD HUM) were obtained in Groups 1 and 2, which means that the deviation value on the HEP perimeter was only slightly higher than the mean deviation value on Humphrey. Therefore, one can conclude that HEP perimeter may detect visual field defects with greater precision. The visual field measurements between ASTA Standard on HEP and SITA Standard on Humphrey as well as ASTA Standard on HEP and SITA Fast on Humphrey are not equal: MD values on HEP perimeter are lower than MD on Humphrey, which can mean that HEP perimeter provides more precise results and shows even early visual field lesions.

CONCLUSIONS
HEP perimeter measures visual field defects with greater precision so it should be taken into consideration for earlier glaucoma detection in routine ophthalmological diagnosis.

Kaczorowski|Kamil|K| Mulak|Małgorzata|M| Szumny|Dorota|D| Baranowska|Marta|M| Jakubaszko-Jabłońska|Joanna|J| Misiuk-Hojło|Marta|M|

visual field
Heidelberg Edge Perimeter
ocular hypertension
glaucoma


Cell infiltrative hydrogel fibrous scaffolds for accelerated wound healing.

Abstract:
Development of natural protein-based fibrous scaffolds with tunable physical properties and biocompatibility is highly desirable to construct three-dimensional (3D), fully cellularized scaffolds for wound healing. Herein, we demonstrated a simple and effective technique to construct electrospun 3D fibrous scaffolds for accelerated wound healing using a photocrosslinkable hydrogel based on gelatin methacryloyl (GelMA). We found that the physical properties of the photocrosslinkable hydrogel including water retention, stiffness, strength, elasticity and degradation can be tailored by changing the light exposure time. We further observed that the optimized hydrogel fibrous scaffolds which were soft and elastic could support cell adhesion, proliferation and migration into the whole scaffolds, facilitating regeneration and formation of cutaneous tissues within two weeks. Such tunable characteristics of the fibrous GelMA scaffolds distinguished them from other reported substrates developed for reconstruction of wound defects including glutaraldehyde-crosslinked gelatin or poly (lactic-co-glycolic acid) (PLGA), whose physical and chemical properties were difficult to modify to allow cell infiltration into the 3D scaffolds for tissue regeneration. We anticipate that the ability to become fully cellularized will make the engineered GelMA fibrous scaffolds suitable for widespread applications as skin substitutes or wound dressings.

STATEMENT OF SIGNIFICANCE
In present study, we generate three-dimensional photocrosslinkable gelatin (GelMA)-based fibrous scaffolds with tunable physical and biological properties by using a combined photocrosslinking/electrospinning approach. The developed GelMA fibrous scaffolds can not only support cell viability and cell adhesion, but also facilitate cell migration and proliferation, accelerating regeneration and formation of cutaneous tissues. In addition, the physical properties of the engineered fibrous GelMA hydrogel including water retention capability, mechanical properties and biodegradability can be tuned to accommodate different patients' needs, making it a promising candidate for skin tissue engineering.

Zhao|Xin|X|
Sun|Xiaoming|X|
Yildirimer|Lara|L|
Lang|Qi|Q|
Lin|Zhi Yuan William|ZYW|
Zheng|Reila|R|
Zhang|Yuguang|Y|
Cui|Wenguo|W|
Annabi|Nasim|N|
Khademhosseini|Ali|A|

D020136:Hydrogel, Polyethylene Glycol Dimethacrylate

D057927:Hydrophobic and Hydrophilic Interactions

D000077182:Polylactic Acid-Polyglycolic Acid Copolymer

Wound healing
Photocrosslinkable hydrogel
Gelatin methacryloyl
Water retention
Soft elasticity


Recent developments in trans-sialidase inhibitors of Trypanosoma cruzi.

Abstract: Chagas is a lethal chronic disease that currently affects 8-10 million people worldwide, primarily in South and Central America. Trypanosoma cruzi trans-sialidase is an enzyme that is of vital importance for the survival of the parasite due to its key role in the transfer of sialic acid from the host to the parasite surface and it also helps the parasite combat the host's immune system. This enzyme has no equivalent human enzyme; thus, it has become an interesting target for the development of inhibitors that combat the parasite. In this review, we summarize three classes of inhibitors (acceptor, donor and unrelated) with their inhibition values and their mode of action against this enzyme. Based on molecular docking, molecular dynamics and structure-activity relationship studies, it has been discovered that the molecules with -NH2, -OH and -COOH groups on an aromatic ring could be used as a scaffold for the development of new and potent trans-sialidase inhibitors due to their key interaction with active enzyme sites. In particular, carboxylic acid derivatives have importance over the sugar moiety due to their ease of synthesis and unique structure-activity relationship.

Kashif|Muhammad|M|
Moreno-Herrera|Antonio|A|
Lara-Ramirez|Edgar E|EE|
Ramírez-Moreno|Esther|E|
Bocanegra-García|Virgilio|V|
Ashfaq|Muhammad|M|
Rivera|Gildardo|G|

D000818:Animals
D001665:Binding Sites
D014355:Chagas Disease
D015195:Drug Design
D004791:Enzyme Inhibitors
D006023:Glycoproteins
D006801:Humans
D062105:Molecular Docking Simulation
D009439:Neuraminidase
D013329:Structure-Activity Relationship
D014344:Trypanocidal Agents
D014349:Trypanosoma cruzi

trans-sialidase
inhibitors
Trypanosoma cruzi
molecular docking
carboxylic acid


Characterization of the Multi-Drug Resistance Gene cfr in Methicillin-Resistant Staphylococcus aureus (MRSA) Strains Isolated From Animals and Humans in China.

Abstract: We investigated cfr-positive and -negative MRSA strains isolated from animals and humans in different geographical areas of China, from 2011 to 2016. Twenty cfr-positive strains (15.6%) were identified from 128 MRSA strains including 17 from food animals and three from humans. The resistance rates and prevalence of the tested antibiotic resistance genes (ARGs) in the cfr-positive MRSA isolates were higher than that in the cfr-negative MRSA isolates. All cfr-positive MRSA isolates were co-carrying fexA and ermC, and had significantly higher optrA incidence rate vs. the cfr-negative isolates (P < 0.05). In addition, multilocus sequence typing (MLST) assays showed that ST9 and spa-type t899 were the most prevalent ST and spa types in the study strains. However, all of the 20 cfr-positive and 10 randomly selected cfr-negative MRSA isolates were clonally unrelated as determined by pulsed-field gel electrophoresis (PFGE) analyses. Importantly, the cfr gene was successfully transferred to a recipient Staphylococcus aureus strain RN4220 from 13 of the 20 cfr-positive MRSA isolates by electroporation. Among these 13 cfr-positive MRSA isolates, two different genetic contexts surrounding cfr were determined and each was associated with one type of cfr-carrying plasmids. Of note, the predominant genetic context of cfr was found to be a Tn558 variant and locate on large plasmids (∼50 kb) co-harboring fexA in 11 of the 13 MRSA isolates. Furthermore, the cfr gene was also identified on small plasmids (∼ 7.1 kb) that co-carried ermC in two of the 13 MRSA isolates. Our results demonstrated a high occurrence of multi-drug resistance in cfr-positive MRSA isolates, and the spread of cfr might be attributed to horizontal dissemination of similar cfr-carrying transposons and plasmids.

Li|Shu-Min|SM| Zhou|Yu-Feng|YF| Li|Liang|L| Fang|Liang-Xing|LX| Duan|Jia-Hong|JH| Liu|Fan-Rui|FR| Liang|Hua-Qing|HQ| Wu|Yu-Ting|YT| Gu|Wei-Qi|WQ| Liao|Xiao-Ping|XP| Sun|Jian|J| Xiong|Yan-Qiong|YQ| Liu|Ya-Hong|YH|

multi-drug resistance
cfr
MRSA
food animals
plasmid


Reduction of adolescent alcohol use through family-school intervention: a randomized trial.

Abstract:
PURPOSE
Two-year longitudinal follow-up data evaluated the behavioral impact of Resilient Families, a universal intervention that aimed to prevent early initiation and frequent and heavy adolescent alcohol use in secondary schools in Melbourne, Australia.

METHODS
Of 24 secondary schools (62% of those approached), 12 were randomly assigned to intervention and 12 as controls. Intervention students received a social relationship curriculum; their parents received parent education handbooks and invitations to parent education events outlining strategies to encourage healthy adolescent development and reduce adolescent alcohol misuse. At Wave 1 (2004), students were in Year 7 secondary school (mean age, 12.3 years). Data were imputed for students completing at least two of three annual surveys (N = 2,354). Wave 3 (2006; mean, 14.5 years) main outcome measures for alcohol use were "any," "frequent" (at least monthly), and "heavy" (five or more drinks in a session at least once in the prior fortnight). Multivariate logistic regression assessed intervention exposure effects, adjusting for school classroom clustering and baseline measures.

RESULTS
Relative to controls, intervention students showed significant reductions in any lifetime use (adjusted odds ratio [AOR], .78; 95% confidence interval [CI], .62-.97), and reduced progression to frequent (AOR, .69; CI, .56-.86) and heavy use (AOR, .75; CI, .60-.94).

CONCLUSIONS
Randomized assignment to Resilient Families was associated with a significant reduction in adolescent alcohol use among families volunteering for the evaluation. Family-school-based interventions appear promising as a strategy to contribute to population reductions in currently high rates of adolescent alcohol misuse.

Toumbourou|John W|JW|
Gregg|M Elizabeth Douglas|ME|
Shortt|Alison L|AL|
Hutchinson|Delyse M|DM|
Slaviero|Tania M|TM|

Adolescent
Alcohol
Intervention
Randomized trial
Family
School


Improving the diagnosis of physical illness in patients with mental illness who present in emergency departments: consensus study.

Abstract:
OBJECTIVE
The aim of this study was to establish consensus among clinicians in order to produce recommendations to optimise the diagnosis of physical illness in patients with mental illness who present in Emergency Departments (EDs).

METHOD
A list of recommendations was derived from qualitative interviews conducted with 39 doctors and nurses working in EDs in four general hospitals in England. Using a modified nominal group technique, we then asked a selected group of 15 doctors and nurses to take part in a group discussion with two voting rounds in order to decide which recommendations are most beneficial and feasible.

RESULTS
Five recommendations met the a priori criteria to be considered 'strongly supported'. These included: having a psychiatric liaison team staff available 24 hours a day in the vicinity of the ED; developing detailed guidelines regarding intoxicated patients and regarding parallel assessment of patients by both ED and psychiatric staff; and having regular meetings between representatives of both departments.

CONCLUSION
In addition to suggesting specific recommendations, the study stresses the advantages in increasing the accessibility of psychiatric staff in the ED but also identifies challenges regarding joint work and division of responsibilities between them and the ED acute team.

Shefer|Guy|G|
Cross|Sean|S|
Howard|Louise M|LM|
Murray|Joanna|J|
Thornicroft|Graham|G|
Henderson|Claire|C|

Consensus
Modified nominal group technique
Diagnostic overshadowing
Emergency medicine
Mental-health
RAND Appropriateness method


Early T follicular helper cell activity accelerates hepatitis C virus-specific B cell expansion.

Abstract: Early appearance of neutralizing antibodies during acute hepatitis C virus (HCV) infection is associated with spontaneous viral clearance. However, the longitudinal changes in antigen-specific memory B cell (MBCs) associated with divergent HCV infection outcomes remain undefined. We characterized longitudinal changes in E2 glycoprotein-specific MBCs from subjects who either spontaneously resolved acute HCV infection or progressed to chronic infection, using single-cell RNA-seq and functional assays. HCV-specific antibodies in plasma from chronically infected subjects recognized multiple E2 genotypes, while those from spontaneous resolvers exhibited variable cross-reactivity to heterotypic E2. E2-specific MBCs from spontaneous resolvers peaked early after infection (4-6 months), following expansion of activated circulating T follicular helper cells (cTfh) expressing interleukin 21. In contrast, E2-specific MBCs from chronically infected subjects, enriched in VH1-69, expanded during persistent infection (> 1 year), in the absence of significantly activated cTfh expansion. Early E2-specific MBCs from spontaneous resolvers produced monoclonal antibodies (mAbs) with fewer somatic hypermutations and lower E2 binding but similar neutralization as mAbs from late E2-specific MBCs of chronically infected subjects. These findings indicate that early cTfh activity accelerates expansion of E2-specific MBCs during acute infection, which might contribute to spontaneous clearance of HCV.

Salinas|Eduardo|E|
Boisvert|Maude|M|
Upadhyay|Amit A|AA|
Bédard|Nathalie|N|
Nelson|Sydney A|SA|
Bruneau|Julie|J|
Derdeyn|Cynthia A|CA|
Marcotrigiano|Joseph|J|
Evans|Matthew J|MJ|
Bosinger|Steven E|SE|
Shoukry|Naglaa H|NH|
Grakoui|Arash|A|

Hepatitis
B cells
Adaptive immunity
Immunology
Infectious disease


Trastuzumab- and Fab' fragment-modified curcumin PEG-PLGA nanoparticles: preparation and evaluation in vitro and in vivo.

Abstract:
Introduction
Nanoparticles (NPs) modified with bio-ligands represent a promising strategy for active targeted drug delivery to tumour. However, many targeted ligands, such as trastuzumab (TMAB), have high molecular weight, limiting their application for targeting. In this study, we prepared Fab' (antigen-binding fragments cut from TMAB)-modified NPs (Fab'-NPs) with curcumin (Cur) as a model drug for more effective targeting of human epidermal growth factor receptor 2 (HER2/ErbB2/Neu), which is overexpressed on breast cancer cells.

Material and methods
The release kinetics was conducted by dialysis bags. The ability to kill HER2-overexpressing BT-474 cells of Fab'-Cur-NPs compared with TMAB-Cur-NPs was conducted by cytotoxicity experiments. Qualitative and quantitative cell uptake studies using coumarin-6 (fluorescent probe)-loaded NPs were performed by fluorescence microscopy and flow cytometry. Pharmacokinetics and biodistribution experiments in vivo were assessed by liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Results
The release kinetics showed that both Fab'-Cur-NPs and TMAB-Cur-NPs provided continuous, slow release of curcumin for 72 h, with no significant difference. In vitro cytotoxicity experiments showed that Fab'-Cur-NPs manifested prominent ability to kill HER2-overexpressing BT-474 cells compared with TMAB-Cur-NPs. Qualitative and quantitative cell uptake studies indicated that the accumulation of Fab'-NPs was greater than that of TMAB-NPs in BT-474 (HER2+) cells; However, there was no significant difference in MDA-MB-231 (HER2-) cells. Pharmacokinetics and biodistribution experiments in vivo demonstrated that the half-life (t1/2) and area under the blood concentration-time curve (AUC0-t) of Fab'-Cur-NPs increased 5.30-fold and 1.76-fold relative to those of TMAB-Cur-NPs, respectively. Furthermore, the tumor accumulation of Fab'-Cur-NPs was higher than that of TMAB-Cur-NPs.

Conclusion
Fab' fragment has greater capacity than the intact antibody to achieve tumor targeting through NP-based delivery.

Duan|Dongyu|D| Wang|Aiping|A| Ni|Ling|L| Zhang|Liping|L| Yan|Xiuju|X| Jiang|Ying|Y| Mu|Hongjie|H| Wu|Zimei|Z| Sun|Kaoxiang|K| Li|Youxin|Y|


Cardiac implantable electronic device remote monitoring surveillance in pediatric and congenital heart disease: Utility relative to frequency.

Abstract:
BACKGROUND
Heart Rhythm Society expert consensus provides recommendations for surveillance monitoring of cardiac implantable electronic devices (CIEDs), but limited data are available for the pediatric and congenital heart disease population.

OBJECTIVE
The purpose of this study was to determine the rate of actionable events during CIED surveillance in this population, assess the utility of routine CIED remote monitoring, and assess the potential benefit from more frequent monitoring.

METHODS
This was a retrospective cohort study of all CIED patients followed at a pediatric and congenital heart center and enrolled in the Medtronic Carelink system with either (1) a chronic (implanted for >6 months) CIED followed between July 1, 2010, and July 1, 2012, on a bimonthly schedule; or (2) a new CIED (implanted <6 months) between July 1, 2008, and July 1, 2012, followed on a monthly schedule.

RESULTS
Aggregate mean age was 20 ± 13.7 years. There were 608 interrogations on newly implanted CIEDs with an actionable event rate of 11 per 100 patient-years. There were 2614 interrogations of chronic CIEDs with an actionable event rate of 22 per 100 patient-years. The odds of an actionable event on an asymptomatic remote monitoring transmission was lower than if symptomatic (odds ratio 0.04, 95% confidence interval 0.03-0.07). Tachyarrhythmia was the most common event. Predictors of actionable events were identified.

CONCLUSION
In this population of pediatric and congenital heart disease patients, the rate of actionable events was low, especially on asymptomatic interrogations. Most actionable events were due to tachyarrhythmia. A more frequent than every 90-day monitoring schedule does not appear to be of significant benefit.

Dechert|Brynn E|BE|
Serwer|Gerald A|GA|
Bradley|David J|DJ|
Dick|Macdonald|M|
LaPage|Martin J|MJ|

D000293:Adolescent
D001145:Arrhythmias, Cardiac
D002648:Child
D002675:Child, Preschool
D017147:Defibrillators, Implantable
D005260:Female
D006330:Heart Defects, Congenital
D006801:Humans
D008297:Male
D008991:Monitoring, Physiologic
D010138:Pacemaker, Artificial
D058998:Remote Sensing Technology
D012189:Retrospective Studies
D013997:Time Factors
D055815:Young Adult

Remote monitoring
Pediatric
Congenital heart disease
Implantable cardioverter-defibrillator
Pacemaker


Cue Combinatorics in Memory Retrieval for Anaphora.

Abstract: Many studies have shown that memory retrieval for real-time language processing relies on a cue-based access mechanism, which allows the cues available at the retrieval site to directly access the target representation in memory. An open question is how different types of cues are combined at retrieval to create a single retrieval probe ("cue combinatorics"). This study addresses this question by testing whether retrieval for antecedent-reflexive dependencies combines cues in a linear (i.e., additive) or nonlinear (i.e., multiplicative) fashion. Results from computational simulations and a reading time experiment show that target items that match all the cues of the reflexive are favored more than target items that mismatch these cues, and that different degrees of mismatches slow reading times in comparable amounts. This profile is consistent with the predictions of a nonlinear cue combination and provides evidence against models in which all cues combine in a linear fashion. A follow-up set of simulations shows that a nonlinear rule also captures previous demonstrations of interference from nontarget items during retrieval for reflexive licensing. Taken together, these results shed new light on how different types of cues combine at the retrieval site and reveal how the method of cue combination impacts the accessibility of linguistic information in memory.

Cue combinatorics
Memory retrieval
Anaphora
Reading times
Computational modeling
Sentence processing


Potential Mechanisms of 3, 4-Oxo-Isopropylidene-Shikimic Acid in Ameliorating 2, 4, 6-Trinitrobenzenesulfonic Acid-Induced Colitis in Rats.

Abstract: Previously, we reported that 3, 4-oxo-isopropylidene-shikimic acid (ISA) has therapeutic potential in experimental colitis in rats. This study aimed to elucidate the potential mechanisms of ISA on the inflammatory response in rats with 2, 4, 6-trinitrobenzenesulfonic acid-induced colitis. After the induction of colitis, rats were orally administered ISA for 12 days. Then, the expression levels of inflammatory cytokines, cell adhesion molecules, and matrix metalloproteinase (MMP) in the blood and colon tissues, and the protein level of nuclear factor kappa B (NF-κB) p65 in cytoplasm and nucleus of colon tissues were evaluated. As a result, an enhanced inflammatory response was observed in rats with experimental colitis. However, the treatment with ISA significantly ameliorated the inflammatory response, which was manifested as a significant decrease in the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, interferon (IFN)-γ, IL-8, TNF-α mRNA, P-selectin, E-selectin, intercellular cell adhesion molecule-1, MMP9 and MMP9 mRNA in rat blood and colon tissues, respectively, and a significant decrease in the levels of IFN-γ/IL-4, and the NF-κBp65 activity coefficient. Therefore, the therapeutic effect of ISA on experimental colitis may be related to its inhibitory effect on the expression of cytokines, adhesion molecules, and MMP9, which may be involved in the inhibition of the activation and nuclear translocation of NF-κBp65.

Yan|Yan|Y| Wang|Pengchong|P| Sun|Ying|Y| Dong|Yalin|Y| Xing|Jianfeng|J|

3
4-oxo-isopropylidene-shikimic acid
cytokine
cell adhesion molecule
nuclear factor kappa B
ulcerative colitis


A model system based on glucose-arginine to monitor the properties of Maillard reaction products.

Abstract: An arginine-glucose mixture (1:2 mol ratio) with pH 9 was heated at 53-100 °C for 10-350 min, and the effects of process parameters were determined during the Maillard reaction (MR). The heating temperature and time were selected as process conditions and were studied with central composite design. The model system was tested based on the values obtained from antioxidant capacity, browning intensity, pH, acrylamide (AC), and hydroxymethylfurfural (HMF) concentrations. Higher temperatures and longer time resulted in higher antioxidant capacity and browning intensity while lowering the pH values. HMF concentration of MR products was found higher in lower temperatures with longer processing time, whereas AC concentration was found higher in high temperatures.

Sogut|Ece|E|0000-0003-4052-993X
Ertekin Filiz|Bilge|B|
Seydim|Atif Can|AC|

Maillard reaction
Acrylamide
Arginine
Glucose
Hyroxymethylfurfural


Intensity of acute aerobic exercise but not aerobic fitness impacts on corticospinal excitability.

Abstract: Aerobic exercise (AE) modulates cortical excitability. It can alter both corticospinal excitability and intra-cortical networks, which has implications for its use as a tool to facilitate processes such as motor learning, where increased levels of excitability are conducive to the induction of neural plasticity. Little is known about how different intensities of AE modulate cortical excitability or how individual-level characteristics impact on it. Therefore, we investigated whether AE intensities, lower than those previously employed, would be effective in increasing cortical excitability. We also examined whether the aerobic fitness of individual participants was related to the magnitude of change in AE-induced cortical excitability. In both experiments we employed transcranial magnetic stimulation to probe corticospinal excitability before and after AE. We show that 20 min of continuous moderate- (40% and 50% of heart rate reserve, HRR), but not low- (30% HRR) intensity AE was effective at increasing corticospinal excitability. We also found that while we observed increased corticospinal excitability following 20 min of continuous moderate-intensity (50% HRR) AE, aerobic fitness was not related to the magnitude of change. Our results suggest that there is a lower bound intensity of AE that is effective at driving changes in cortical excitability, and that while individual-level characteristics are important predictors of response to AE, aerobic fitness is not. Overall these findings have implication for the way that AE is used to facilitate processes such as motor learning, where increased levels of cortical excitability and plasticity are favourable.

MacDonald|Monica A|MA|
Khan|Hawazin|H|
Kraeutner|Sarah N|SN|
Usai|Francesco|F|
Rogers|Emily A|EA|
Kimmerly|Derek S|DS|
Dechman|Gail|G|
Boe|Shaun G|SG|

aerobic exercise
aerobic fitness
corticospinal excitability
plasticity
transcranial magnetic stimulation
activité physique
capacité aérobie
excitabilité corticospinale
exercice aérobie
physical activity
plasticité
stimulation magnétique transcrânienne


A single center retrospective study of paraneoplastic neurological syndromes with positive onconeural antibodies.

Abstract: Paraneoplastic neurological syndromes (PNS) are rare immune-mediated disorders, and the detection of onconeural antibodies is helpful for PNS diagnosis. The aim of this study was to investigate the clinical characteristics of patients with PNS with positive onconeural antibodies in a single center in Hubei, China. We retrospectively analyzed the clinical characteristics of 54 patients with positive onconeural antibodies from January 2016 to September 2020. Among 780 patients with suspected PNS, 54 (6.9%) had positive onconeural antibodies. Of those 54 patients, 28 (51.8%) were diagnosed with definite PNS and 13 (24.1%) with possible PNS. Eighteen (33.3%) patients were confirmed with cancer. Ten PNS syndromes were detected among the 28 patients with definite PNS, and they had either classical (12/28, 42.8%) or non-classical syndromes (17/28, 60.7%). Peripheral neuropathy (9/28, 32.1%), subacute cerebellar degeneration (4/28, 14.3%), and limbic encephalitis (4/28, 14.3%) were the most common PNS syndromes. The anti-CV2/CRMP5-antibody was observed most frequently. Lung cancer was the most common tumor type. For patients with possible PNS, peripheral neuropathy was the most common PNS syndrome, and the anti-Tr-antibody was the most frequent onconeural antibody. Immunotherapy was effective in treating PNS. The anti-CV2/CRMP5-antibody was the most subsequently observed antibody. The manifestations of PNS are diverse and include peripheral neuropathy, subacute cerebellar degeneration, and limbic encephalitis. In patients with PNS, lung cancer was the most common tumor.

Fu|Peicai|P| He|Lilin|L| Tang|Na|N| Nie|Qing|Q| Li|Zhijun|Z|

D020361:Paraneoplastic Syndromes, Nervous System

D010523:Peripheral Nervous System Diseases

Paraneoplastic neurological syndromes
Onconeural antibodies
Peripheral neuropathy
Subacute cerebellar degeneration
Limbic encephalitis
Tumors
Immunotherapy


Comparison of antimüllerian hormone levels and antral follicle count as predictor of ovarian response to controlled ovarian stimulation in good-prognosis patients at individual fertility clinics in two multicenter trials.

Abstract:
OBJECTIVE
To compare antimüllerian hormone (AMH) and antral follicle count (AFC) as predictors of ovarian response to controlled ovarian stimulation at individual fertility clinics.

DESIGN
Retrospective analysis of individual study center data in two multicenter trials. Centers that provided >10 patients were included in the analysis.

SETTING
A total of 19 (n = 519 patients) and 18 study centers (n = 686 patients) participating in a long GnRH agonist trial (MERIT) and a GnRH antagonist trial (MEGASET), respectively.

PATIENT(S)
Infertile women of good prognosis.

INTERVENTION(S)
Long GnRH agonist or GnRH antagonist cycles.

MAIN OUTCOME MEASURE(S)
Correlation between AMH and AFC, and oocyte yield by each study center for each trial.

RESULTS(S)
Antimüllerian hormone was more strongly correlated with oocyte yield than AFC: r = 0.56 vs. r = 0.28 in the GnRH agonist cohort, and r = 0.55 vs. r = 0.33 in the GnRH antagonist cohort. The correlation was numerically higher for AMH than for AFC at a significantly higher proportion of study centers: 17 (89%) and 15 (83%) centers in the long GnRH agonist and GnRH antagonist trial, respectively. Assessment of the relative capacity of AMH and AFC for predicting oocyte yield demonstrated that AMH dominated the model: AMH, R(2) = 0.29 and 0.23; AFC: R(2) = 0.07 and 0.07; AMH + AFC: R(2) = 0.30 and 0.23 for long GnRH agonist and GnRH antagonist trials, respectively.

CONCLUSIONS(S)
Antimüllerian hormone was a stronger predictor of ovarian response to gonadotropin therapy than AFC at the study center level in both randomized trials utilizing GnRH agonist and GnRH antagonist protocols. Antral follicle count provided no added predictive value beyond AMH.

Nelson|Scott M|SM|
Klein|Bjarke M|BM|
Arce|Joan-Carles|JC|

Antimüllerian hormone
antral follicle count
ovarian response
IVF clinic
multicenter randomized controlled trial


Changes during leaf expansion of ΦPSII temperature optima in Gossypium hirsutum are associated with the degree of fatty acid lipid saturation.

Abstract: In this project, we hypothesize that cotton (Gossypium hirsutum) leaf temperature and the responses of leaf photosynthesis to temperature will change as the leaves expand and that differences between young and mature leaves will be associated with the proportion of saturated fatty acids in thylakoid and other membrane lipids. To that end, we studied main stem leaves obtained from plants growing in a temperature controlled greenhouse and at different times in the field season. We found that young leaves (∼5d old) had higher mid day temperatures, lower stomatal conductance and higher thermal optima as measured by ΦPSII temperature curves than did more mature leaves (∼13d old). Young leaves also had significant differences in fatty acid saturation with the warmer, young leaves having a higher proportion of palmitic acid (16:0) and lower linoleic acid (18:3) in total lipid extracts and higher 16:0 and lower palmitoleic acid (16:1) in the chloroplast membrane phosphoglycerides, digalactosyldiacylglycerol (in the greenhouse) and phosphatidylglycerol when compared with cooler, more mature leaves. Later in the growing season, leaf temperature, stomatal conductance and ΦPSII temperature curves for young and more mature leaves were similar and the proportion of 16:0 fatty acids decreased and 16:1 increased in phosphatidylglycerol. We conclude that changes in temperature as cotton leaves expand leads to alterations in the fatty acid composition of thylakoid and other membranes and, consequently, influence photosynthesis/temperature responses.

Hall|Trent D|TD|
Chastain|Daryl R|DR|
Horn|Patrick J|PJ|
Chapman|Kent D|KD|
Choinski|John S|JS|

Leaf expansion
Gossypium hirsutum
Fatty acid saturation
Chlorophyll fluorescence
Photosynthetic thermotolerance


ASK1/p38‑mediated NLRP3 inflammasome signaling pathway contributes to aberrant retinal angiogenesis in diabetic retinopathy.

Abstract: Diabetic retinopathy (DR) is the leading cause of blindness among the working‑age population in several countries. Despite the available treatments, some patients are diagnosed at the late stages of the disease when treatment is more difficult. Hence, it is crucial that novel targets are identified in order to improve the clinical therapy of DR. In the present study, an animal model of DR and a cell model using primary human retinal microvascular endothelial cells exposed to high glucose were constructed to examine the association between apoptosis signal‑regulating kinase 1 (ASK1)/p38 and NLR family pyrin domain containing 3 (NLRP3) in DR. The results revealed that DR induced inflammatory response and microvascular cell proliferation. NLRP3 contributed to DR‑mediated inflammatory development and progression, which promoted the expression of inflammatory‑related cytokines. In addition, NLRP3 promoted the tube formation of retinal microvascular endothelial cells and angiogenesis. Moreover, further research indicated that the NLRP3‑mediated aberrant retinal angiogenesis in DR was regulated by ASK1 and p38. It was thus suggested that ASK1/p38 may be novel target for the treatment of DR.

Zou|Wenjun|W| Luo|Shasha|S| Zhang|Zhengwei|Z| Cheng|Libo|L| Huang|Xiaoli|X| Ding|Nannan|N| Pan|Ying|Y| Wu|Zhifeng|Z|

D000071199:NLR Family, Pyrin Domain-Containing 3 Protein

D048051:p38 Mitogen-Activated Protein Kinases


A synopsis of knowledge, zoogeography and an online interactive map of Brazilian marine gastrotrichs.

Abstract: Information regarding the records of Brazilian marine gastrotrichs is presented. We systematized and organized the existing information associated with approximately 23 species (belonging to the genera Aspidiophorus, Chaetonotus, Crasiella, Dactylopodola, Dendrodasys, Draculiciteria, Halichaetonotus, Heteroxenotrichula, Kryptodasys, Macrodasys, Pseudostomella, Ptychostomella, Urodasys and Xenotrichula) from the Brazilian coast (eight endemic) and their 1,581 records from 36 marine ecoregions of the world. A link is provided to an on-line interactive map where all occurrences for each species are shown, accompanied by geographic coordinates, oceans, countries, cities, granulometric characteristics and ecoregions. Furthermore, a critical analysis of the geographical distribution of Brazilian marine gastrotrichs, an estimate of the number of undescribed species, a summary of the existence and status of taxonomical collections are also presented.

Biodiversity
Chaetonotida
Gastrotricha
Macrodasyida
Species distribution


A new method to model electroconvulsive therapy in rats with increased construct validity and enhanced translational value.

Abstract: Electroconvulsive therapy is the most effective therapy for major depressive disorder (MDD). The remission rate is above 50% in previously pharmacoresistant patients but the mechanisms of action are not fully understood. Electroconvulsive stimulation (ECS) in rodents mimics antidepressant electroconvulsive therapy (ECT) in humans and is widely used to investigate the underlying mechanisms of ECT. For the translational value of findings in animal models it is essential to establish models with the highest construct, face and predictive validity possible. The commonly used model for ECT in rodents does not meet the demand for high construct validity. For ECT, cortical surface electrodes are used to induce therapeutic seizures whereas ECS in rodents is exclusively performed by auricular or corneal electrodes. However, the stimulation site has a major impact on the type and spread of the induced seizure activity and its antidepressant effect. We propose a method in which ECS is performed by screw electrodes placed above the motor cortex of rats to closely simulate the clinical situation and thereby increase the construct validity of the model. Cortical ECS in rats induced reliably seizures comparable to human ECT. Cortical ECS was more effective than auricular ECS to reduce immobility in the forced swim test. Importantly, auricular stimulation had a negative influence on the general health condition of the rats with signs of fear during the stimulation sessions. These results suggest that auricular ECS in rats is not a suitable ECT model. Cortical ECS in rats promises to be a valid method to mimic ECT.

Theilmann|Wiebke|W| Löscher|Wolfgang|W| Socala|Katarzyna|K| Frieling|Helge|H| Bleich|Stefan|S| Brandt|Claudia|C|

Electroconvulsive therapy
Rat
Major depressive disorder
ECS
ECT
Animal model


Analysis of the Empathic Concern Subscale of the Emotional Response Questionnaire in a Study Evaluating the Impact of a 3D Cultural Simulation.

Abstract: Abstract Background Empathic concern has been found to decline in health professional students. Few effective educational programs and a lack of validated scales are reported. Previous analysis of the Empathic Concern scale of the Emotional Response Questionnaire has reported both one and two latent constructs. Aim To evaluate the impact of simulation on nursing students' empathic concern and test the psychometric properties of the Empathic Concern scale. Methods The study used a one group pre-test post-test design with a convenience sample of 460 nursing students. Empathic concern was measured pre-post simulation with the Empathic Concern scale. Factor Analysis was undertaken to investigate the structure of the scale. Results There was a statistically significant increase in Empathic Concern scores between pre-simulation 5.57 (SD = 1.04) and post-simulation 6.10 (SD = 0.95). Factor analysis of the Empathic Concern scale identified one latent dimension. Conclusion Immersive simulation may promote empathic concern. The Empathic Concern scale measured a single latent construct in this cohort.

Everson|Naleya|N|
Levett-Jones|Tracy|T|
Pitt|Victoria|V|
Lapkin|Samuel|S|
Van Der Riet|Pamela|P|
Rossiter|Rachel|R|
Jones|Donovan|D|
Gilligan|Conor|C|
Courtney Pratt|Helen|H|

culture simulation compassion empathic-concern


Spectral and photophysical modifications of porphyrins attached to core-shell nanoparticles. Theory and experiment.

Abstract: Plasmonic nanostructures, of which gold nanoparticles are the most elementary example, owe their unique properties to localized surface plasmons (LSP), the modes of free electron oscillation. LSP alter significantly electromagnetic field in the nanostructure neighborhood (i.e., near-field), which can modify the electric dipole transition rates in organic emitters. This study aims at investigating the influence of Au@SiO2core-shell nanoparticles on the photophysics of porphyrins covalently attached to the nanoparticles surface. Guided by theoretical predictions, three sets of gold nanoparticles of different sizes were coated with a silica layer of similar thickness. The outer silica surface was functionalized with either free-basemeso-tetraphenylporphyrin or its zinc complex. Absorption and emission bands of porphyrin overlap in energy with a gold nanoparticle LSP resonance that provides the field enhancement. Silica separates the emitters from the gold surface, while the gold core size tunes the energy of the LSP resonance. The signatures of weak-coupling regime have been observed. Apart from modified emission profiles and shortened S1lifetimes, Q band part intensity of the excitation spectra significantly increased with respect to the Soret band. The results were explained using classical transfer matrix simulations and electronic states kinetics, taking into account the photophysical properties of each chromophore. The calculations could reasonably well predict and explain the experimental outcomes. The discrepancies between the two were discussed.

porphyrin
plasmonics
core–shell nanoparticles
fluorescence


New in vitro model for proarrhythmia safety screening: IKs inhibition potentiates the QTc prolonging effect of IKr inhibitors in isolated guinea pig hearts.

Abstract:
INTRODUCTION
Preclinical in vivo QT measurement as a proarrhythmia essay is expensive and not reliable enough. The aim of the present study was to develop a sensitive, cost-effective, Langendorff perfused guinea pig heart model for proarrhythmia safety screening.

METHODS
Low concentrations of dofetilide and cisapride (inhibitors of the rapid delayed rectifier potassium current, IKr) were tested alone and co-perfused with HMR-1556 (inhibitor of the slow delayed rectifier potassium current, IKs) in Langendorff perfused guinea pig hearts. The electrocardiographic rate corrected QT (QTc) interval, the Tpeak-Tend interval and the beat-to-beat variability and instability (BVI) of the QT interval were determined in sinus rhythm.

RESULTS
Dofetilide and HMR-1556 alone or co-perfused, prolonged the QTc interval by 20±2%, 10±1% and 55±10%, respectively. Similarly, cisapride and HMR-1556 alone or co-perfused, prolonged the QTc interval by 11±3%, 11±4% and 38±6%, respectively. Catecholamine-induced fast heart rate abolished the QTc prolonging effects of the IKr inhibitors, but augmented the QTc prolongation during IKs inhibition. None of the drug perfusions increased significantly the Tpeak-Tend interval and the sinus BVI of the QT interval.

DISCUSSION
IKs inhibition increased the QTc prolonging effect of IKr inhibitors in a super-additive (synergistic) manner, and the QTc interval was superior to other proarrhythmia biomarkers measured in sinus rhythm in isolated guinea pig hearts. The effect of catecholamines on the QTc facilitated differentiation between IKr and IKs inhibitors. Thus, QTc measurement in Langendorff perfused guinea pig hearts with pharmacologically attenuated repolarization reserve and periodic catecholamine perfusion seems to be suitable for preclinical proarrhythmia screening.

Kui|Péter|P|
Orosz|Szabolcs|S|
Takács|Hedvig|H|
Sarusi|Annamária|A|
Csík|Norbert|N|
Rárosi|Ferenc|F|
Csekő|Csongor|C|
Varró|András|A|
Papp|Julius Gy|JG|
Forster|Tamás|T|
Farkas|Attila S|AS|
Farkas|András|A|

D051668:Delayed Rectifier Potassium Channels

Proarrhythmia
Safety screening
Guinea pig hearts
Langendorff perfusion
Methods
Repolarization reserve
ECG
Rate corrected QT interval
Synergism
Torsades de pointes


60 Minutes for health: examining the feasibility and acceptability of a low-resource behavioral intervention designed to promote retention in HIV care.

Abstract: Sustained retention in HIV medical care is a key health behavior for the long-term health of people living with HIV (PLWH). Approximately 60% of PLWH in the U.S. are poorly retained in HIV care, yet to date, the few available evidence-based retention-promoting interventions are resource and time intensive to implement. The current study describes the feasibility and acceptability of a theory-based retention-promoting intervention designed to meet the needs of a busy clinical care setting. 60 Minutes for Health reflects a low-resource single-session intervention, implemented by a health educator, to PLWH who have had a recent gap in care (≥6-months) in the past 18-months. Intervention content was informed by a situated application of the Information Motivation Behavioral Skills Model and delivered using a Motivational Interviewing-based format. The intervention uses a workbook to guide a series of activities that: (1) Identify and reduce misinformation guiding HIV care attendance. (2) Enhance motivation to maintain care via personal health goals. (3) Build skills for coping with emotional distress related to living with HIV. (4) Increase self-efficacy for navigating the logistics of maintaining care amidst competing priorities. A small feasibility pilot of this intervention protocol was conducted to assess its potential to improve retention in care and to obtain estimates for a larger-scale efficacy trial. Participants were randomized to the 60-minute intervention session (n = 8), or a theory-based time-and-attention control session focused on diet and nutrition (n = 8). Medical records were abstracted to evaluate changes in participants' retention in care status at 12- and 24-months post-intervention. Findings suggest the intervention is both feasible and acceptable to implement with poorly retained PLWH in a clinic setting. Post-intervention a larger proportion of intervention participants were retained in care (12-months: 87.5%, 24-months: 62.5%), compared control participants (12-months: 50.0%, 24-months: 25.0%). Future work should aim to evaluate a larger-scale efficacy trial.

Smith|Laramie R|LR|
Amico|K Rivet|KR|
Fisher|Jeffrey D|JD|
Cunningham|Chinazo O|CO|

D010342:Patient Acceptance of Health Care

HIV
theory-based
retention in care
brief intervention


Evaluation of conditioned medium from placenta-derived mesenchymal stem cells as a storage medium for avulsed teeth: An in vitro study.

Abstract:
BACKGROUND/AIM
The viability of periodontal ligament cells on the root surface is a major factor that influences the healing of replanted teeth. A suitable storage medium is necessary to preserve avulsed teeth before replantation. Conditioned medium from placenta-derived mesenchymal stem cells (PMSC-CM) contains a variety of growth factors. The aim of this study was to evaluate the effectiveness of PMSC-CM as a storage medium to maintain the cell viability of avulsed teeth.

MATERIAL AND METHODS
Extracted premolars from healthy humans were randomly stored in Hank's balanced salt solution (HBSS) and PMSC-CM for 6, 12 and 24 hours, respectively, at room temperature, and then the ratio of apoptosis of the periodontal ligament (PDL) cells was identified by flow cytometry. Human periodontal ligament stem cells (PDLSCs) were incubated with HBSS and PMSC-CM, respectively, for 6, 12, 24 and 48 hours in 5% CO2 at 37°C. Then, the cell viability of PDLSCs was determined using the cell counting kit-8 (CCK-8) and a cell cycle assay was performed.

RESULTS
The apoptosis rate of PDL cells in PMSC-CM was significantly lower than that in HBSS at 24 hours (P < .001), while the two groups showed similar cell apoptosis rates at 6 and 12 hours (P > .05). The cell proliferation of PDLSCs treated with PMSC-CM significantly increased compared with the HBSS group (P < .05). The cell cycle assay revealed that the PDLSCs treated with HBSS were arrested at the G1 phase, while there was no difference between the PMSC-CM group and the control group (P > .05).

CONCLUSIONS
Compared with HBSS, PMSC-CM showed better inhibition of apoptosis of PDL cells and promoted the proliferation of PDLSCs. Thus, PMSC-CM could be a promising storage medium for avulsed teeth.


A major facilitator superfamily domain 8 frameshift variant in a cat with suspected neuronal ceroid lipofuscinosis.

Abstract: A 2-year-old male domestic shorthair cat was presented for a progressive history of abnormal posture, behavior, and mentation. Menace response was absent bilaterally, and generalized tremors were identified on neurological examination. A neuroanatomical diagnosis of diffuse brain dysfunction was made. A neurodegenerative disorder was suspected. Magnetic resonance imaging findings further supported the clinical suspicion. Whole-genome sequencing of the affected cat with filtering of variants against a database of unaffected cats was performed. Candidate variants were confirmed by Sanger sequencing followed by genotyping of a control population. Two homozygous private (unique to individual or families and therefore absent from the breed-matched controlled population) protein-changing variants in the major facilitator superfamily domain 8 (MFSD8) gene, a known candidate gene for neuronal ceroid lipofuscinosis type 7 (CLN7), were identified. The affected cat was homozygous for the alternative allele at both variants. This is the first report of a pathogenic alteration of the MFSD8 gene in a cat strongly suspected to have CLN7.

cat
neuronal ceroid lipofuscinosis
MFSD8
NCL7
genetics
lysosomal storage disease
precision medicine


Ringed seal (Pusa hispida) seasonal movements, diving, and haul-out behavior in the Beaufort, Chukchi, and Bering Seas (2011-2017).

Abstract: Continued Arctic warming and sea-ice loss will have important implications for the conservation of ringed seals, a highly ice-dependent species. A better understanding of their spatial ecology will help characterize emerging ecological trends and inform management decisions. We deployed satellite transmitters on ringed seals in the summers of 2011, 2014, and 2016 near Utqiaġvik (formerly Barrow), Alaska, to monitor their movements, diving, and haul-out behavior. We present analyses of tracking and dive data provided by 17 seals that were tracked until at least January of the following year. Seals mostly ranged north of Utqiaġvik in the Beaufort and Chukchi Seas during summer before moving into the southern Chukchi and Bering Seas during winter. In all seasons, ringed seals occupied a diversity of habitats and spatial distributions, from near shore and localized, to far offshore and wide-ranging in drifting sea ice. Continental shelf waters were occupied for >96% of tracking days, during which repetitive diving (suggestive of foraging) primarily to the seafloor was the most frequent activity. From mid-summer to early fall, 12 seals made ~1-week forays off-shelf to the deep Arctic Basin, most reaching the retreating pack-ice, where they spent most of their time hauled out. Diel activity patterns suggested greater allocation of foraging efforts to midday hours. Haul-out patterns were complementary, occurring mostly at night until April-May when midday hours were preferred. Ringed seals captured in 2011-concurrent with an unusual mortality event that affected all ice-seal species-differed morphologically and behaviorally from seals captured in other years. Speculations about the physiology of molting and its role in energetics, habitat use, and behavior are discussed; along with possible evidence of purported ringed seal ecotypes.

Arctic
spatial ecology
Alaska
unusual mortality event
ecotype
marine mammals
phocid
satellite telemetry


Current treatment options for management of anal intraepithelial neoplasia.

Abstract: Anal squamous cell cancer is an uncommon malignancy caused by infection with oncogenic strains of Human papilloma virus. Anal cancer is much more common in immunocompromised persons, including those infected with Human immunodeficiency virus. High-grade anal intraepithelial neoplasia (HGAIN), the precursor of anal cancer, is identified by clinicians providing care for patients with anorectal disease, and is increasingly being identified during screening of immunosuppressed patients for anal dysplasia. The traditional treatment for HGAIN has been excision of macroscopic disease with margins. This approach is effective for patients with small unifocal HGAIN lesions. Patients with extensive multifocal HGAIN frequently have recurrence of HGAIN after excision, and may have postoperative complications of anal stenosis or fecal incontinence. This led to the suggestion by some that treatment for HGAIN should be delayed until patients developed anal cancer. Alternative approaches in identification and treatment have been developed to treat patients with multifocal or extensive HGAIN lesions. High-resolution anoscopy combines magnification with anoscopy and is being used to identify HGAIN and determine treatment margins. HGAIN can then be ablated with a number of modalities, including infrared coagulation, CO2 laser, and electrocautery. These methods for HGAIN ablation can be performed with local anesthesia on outpatients and are relatively well tolerated. High-resolution anoscopy-directed HGAIN ablation is evolving into a standard approach for initial treatment and then subsequent monitoring of a disease which should be expected to be recurrent. Another treatment approach for HGAIN is topical treatment, principally with 5-fluorouracil or imiquimod. Topical therapies have the advantage of being nonsurgical and are well suited for treating widespread multifocal disease. Topical treatments have the disadvantage of requiring extended treatment courses and causing a symptomatic inflammatory response. Successful treatment requires adherence to a regime that is uncomfortable at best and at worst painful. Topical treatments can be successful in motivated adherent patients willing to accept these side effects.

human papilloma virus
anal cancer
anal dysplasia
high-resolution anoscopy
infrared coagulation
perianal dermatosis


Fez family transcription factors: controlling neurogenesis and cell fate in the developing mammalian nervous system.

Abstract: Fezf1 and Fezf2 are highly conserved transcription factors that were first identified by their specific expression in the anterior neuroepithelium of Xenopus and zebrafish embryos. These proteins share an N-terminal domain with homology to the canonical engrailed repressor motif and a C-terminal DNA binding domain containing six C2H2 zinc-finger repeats. Over a decade of study indicates that the Fez proteins play critical roles during nervous system development in species as diverse as fruit flies and mice. Herein we discuss recent progress in understanding the functions of Fezf1 and Fezf2 in neurogenesis and cell fate specification during mammalian nervous system development. Going forward we believe that efforts should focus on understanding how expression of these factors is precisely regulated, and on identifying target DNA sequences and interacting partners. Such knowledge may reveal the mechanisms by which Fezf1 and Fezf2 accomplish both independent and redundant functions across diverse tissue and cell types.

D018507:Gene Expression Regulation, Developmental

neurogenesis
cell fate
Fezf1
Fezf2
cerebral cortex
gene expression
olfactory system


Development and Characterization of Cell-Specific Androgen Receptor Knockout Mice.

Abstract: Conditional gene targeting has revolutionized molecular genetic analysis of nuclear receptor proteins, however development and analysis of such conditional knockouts is far from simple, with many caveats and pitfalls waiting to snare the novice or unprepared. In this chapter, we describe our experience of generating and analyzing mouse models with conditional ablation of the androgen receptor (AR) from tissues of the reproductive system and other organs. The guidance, suggestions, and protocols outlined in the chapter provide the key starting point for analyses of conditional-ARKO mice, completing them as described provides an excellent framework for further focussed project-specific analyses, and applies equally well to analysis of reproductive tissues from any mouse model generated through conditional gene targeting.

D060888:Real-Time Polymerase Chain Reaction

Androgen receptor
Conditional knockout
Mouse
ARKO
Cre/lox
Transgenic


Delusion, excitement, violence, and suicide history are risk factors for aggressive behavior in general inpatients with serious mental illnesses: A multicenter study in China.

Abstract: Little is known about the risk factors for aggression in general clinical settings in China. The aim of this study is to explore potential risk factors for inpatients with serious mental illness. The study was conducted from 15 March to 14 April 2013 and involved 16 general psychiatric institutions in China. A standardized data collection form was used to collect demographic and clinical characteristics data, including information on current hallucinations, delusions, depression, excitement, aboulia, apathy, and adherence to treatment. Information on lifetime history of violence and suicidality was also collected. The Modified Overt Aggression Scale (MOAS) was also administered to indicate recent (past week) aggression. A total of 511 inpatients were enrolled. On the basis of a score of five or greater on the MOAS, 245 inpatients were assigned to aggressive group and 266 were assigned to non-aggressive group. A lifetime history of violent behaviour (OR = 3.1, 95% CI = 1.95-5.11), suicide (OR = 3.0, 95% CI = 1.49-6.10), as well as current delusions (OR = 1.92, 95% CI = 1.24-2.97), and excitement (OR = 2.63, 95% CI = 1.57-4.39) were associated with aggression. The study suggested violent history, suicide history, current delusions, and excitement are the risk factors for aggression among general psychiatric inpatients with serious mental illnesses.

Li|Qiguang|Q| Zhong|Shaoling|S| Zhou|Jiansong|J| Wang|Xiaoping|X|

Violence
Suicide
Risk factor
Aggressive behavior
Serious mental illness


Sacral plexus disorder caused by a wooden toothpick in the rectum.

Abstract: A 67-year-old man presented with a 2-month history of pain in his right buttock and lower limb. MRI depicted right L5/S1 lateral recess stenosis requiring surgical treatment; however, preoperative CT showed an approximately 7 cm long, thin, rod-shaped structure in the rectum, which was ultimately determined to be an accidentally ingested toothpick. It was removed surgically 6 days after diagnosis, because right leg pain worsened rapidly. The pain disappeared thereafter, and the symptoms have not recurred since. The pain might have been localised to the right buttock and posterior thigh in the early stages because the fine tip of the toothpick was positioned to the right of the anterior ramus of the S2 spinal nerve. Although sacral plexus disorder caused by a rectal foreign body is extremely rare, physicians should be mindful to avoid misdiagnosis.

pain (neurology)
peripheral nerve disease
spinal cord


Trace elements and omega-3 fatty acids of black sea (Bulgaria) bivalve species Mytilus galloprovincialis, Chamelea gallina and Donax trunculus. Human health risk.

Abstract: The study aimed to evaluate trace elements (Cd, Cr, Cu, Fe, Ni, Pb and Zn) concentrations and fatty acids of three Black Sea bivalve species - Donax trunculus, Mytilus galloprovincialis and Chamelea gallina as well as human health risk and benefit-risk ratio based on n-3 LC-PUFA vs. toxic/essential elements. The results showed variations in the element concentrations among the analysed species. D. trunculus generally contained higher levels of the essential elements Cu and Zn, while C. gallina - higher Cr and Fe. Toxic elements content did not exceed the international standards for mollusks. D. trunculus and C. gallina were better dietary sources of n-3 LC-PUFA, with approximately two-fold higher EPA + DHA content than M. galloprovincialis. Health risks for most toxic and essential elements exposed from bivalve consumption were safe based on THQ, HI and TR indices. The benefit-risk ratio indicated that studied species are safe for human consumption, except one case.

trace elements
fatty acids
Black Sea
bivalves
human health risk
risk-benefit


Multivariate tests based on interpoint distances with application to magnetic resonance imaging.

Abstract: The multivariate location problem is addressed. The most familiar method to address the problem is the Hotelling test. When the hypothesis of normal distributions holds, the Hotelling test is optimal. Unfortunately, in practice the distributions underlying the samples are generally unknown and without assuming normality the finite sample unbiasedness of the Hotelling test is not guaranteed. Moreover, high-dimensional data are increasingly encountered when analyzing medical and biological problems, and in these situations the Hotelling test performs poorly or cannot be computed. A test that is unbiased for non-normal data, for small sample sizes as well as for two-sided alternatives and that can be computed for high-dimensional data has been recently proposed and is based on the ranks of the interpoint Euclidean distances between observations. Five modifications of this test are proposed and compared to the original test and the Hotelling test. Unbiasedness and consistency of the tests are proven and the problem of power computation is addressed. It is shown that two of the modified interpoint distance-based tests are always more powerful than the original test. Particularly, the modified test based on the Tippett criterium is suggested when the assumption of normality is not tenable and/or in case of high-dimensional data with complex dependence structure which are typical in molecular biology and medical imaging. A practical application to a case-control study where functional magnetic resonance imaging is used is discussed.

interpoint distance
high-dimensional data
case-control study
hypothesis testing
nonparametric tests


Identification and characterisation of carnostatine (SAN9812), a potent and selective carnosinase (CN1) inhibitor with in vivo activity.

Abstract: Carnosinase 1 (CN1) has been postulated to be a susceptibility factor for developing diabetic nephropathy (DN). Although its major substrate, carnosine, is beneficial in rodent models of DN, translation of these findings to humans has been hampered by high CN1 activity in human serum resulting in rapid degradation of carnosine. To overcome this hurdle, we screened a protease-directed small-molecule library for inhibitors of human recombinant CN1. We identified SAN9812 as a potent and highly selective inhibitor of CN1 activity with a Ki of 11 nM. It also inhibited CN1 activity in human serum and serum of transgenic mice-overexpressing human CN1. Subcutaneous administration of 30 mg/kg SAN9812 led to a sustained reduction in circulating CN1 activity in human CN1 transgenic (TG) mice. Simultaneous administration of carnosine and SAN9812 increased carnosine levels in plasma and kidney by up to 100-fold compared to treatment-naïve CN1-overexpressing mice. To our knowledge, this is the first study reporting on a potent and selective CN1 inhibitor with in vivo activity. SAN9812, also called carnostatine, may be used to increase renal carnosine concentration as a potential therapeutic modality for renal diseases linked to glycoxidative conditions.

Diabetic nephropathies
Carnosine
Aminoacyl-histidine dipeptidase
Drug discovery


An 8-year population description from a national treatment centre on lymphatic malformations.

Abstract:
INTRODUCTION
Lymphatic malformations are rare developmental non-malignant abnormalities that present as masses consisting of abnormal growth of fluid filled channels or spaces in the skin or deep tissue that result in abnormalities of lymphatic flow. They may cause symptoms like pain, recurrent lymphorrea, abnormal bone growth, and disturbance of bodily functions. They may also be a cosmetic problem. The study aims to describe the population with lymphatic malformations (LM) treated at a national referral centre.

MATERIALS AND METHODS
This is a retrospective review of patients with the diagnosis lymphatic malformation seen at the centre between 2006-2013. The authors performed a systematic review of the hospital records and a reevaluation of the radiological findings. Eighty-five patients with 102 lymphatic malformations were included.

RESULTS
The majority of the patients (67%) were diagnosed before the age of 2 years. Lesions were located mainly to the head and neck (64%) and half (52%) were macrocystic. Treatment was: sclerotherapy (69%), surgery (49%), laser therapy (19%), or a combination of these treatment modalities (33%). The best outcome was found in the patients with macrocystic lesions (p = .029), and 76% of the patients reported a good or very good outcome.

CONCLUSION
Most patients presented before the age of 2 years with complex lesions which required unique, often multimodal treatment plans and in general they experienced good outcome.

Eliasson|Jill Josefine|JJ|
Weiss|Inanna|I|
Høgevold|Hans Erik|HE|
Oliver|Nina|N|
Andersen|Rune|R|
Try|Kirsti|K|
Tønseth|Kim Alexander|KA|

Lymphatic malformation
macrocystic
sclerotherapy
surgery
cystic hygroma
liposuction
lymphangioma
microcystic


Circulating anti-inflammatory adipokines High Molecular Weight Adiponectin and Zinc-α2-glycoprotein (ZAG) are inhibited in early sepsis, but increase with clinical recovery: a pilot study.

Abstract:
BACKGROUND
Adipose tissue has been identified as an endocrine organ secreting adipokines involved in metabolic and inflammatory pathways. Adiponectin, an anti-inflammatory adipokine, is reduced in sepsis. High Molecular Weight (HMW) adiponectin, the biologically most relevant molecule, has been investigated very little in human sepsis. Zinc-alpha2-glycoprotein (ZAG) is a novel adipokine and its expression in adipose tissue is positively correlated with adiponectin expression. It is not yet known whether ZAG has a role in sepsis. In this study we assessed levels of HMW adiponectin and ZAG during different stages of sepsis.

METHODS
A prospective observational pilot study was carried out on 21 septic patients. Serum samples were taken on day 1 and 2 post ICU admission and on day of discharge. Samples were analysed for total and HMW adiponectin, HMW/total adiponectin ratio, and ZAG. Results were correlated with clinical and metabolic data.

RESULTS
There were no differences in total adiponectin, HMW adiponectin and ZAG plasma concentrations between day 1 (admission) and day 2 of the sepsis episode. Compared to admission, a significant increase in total and HMW adiponectin and ZAG was observed on the day of discharge when clinical improvement had been achieved. There was also an increase in the HMW/total adiponectin ratio at that time.

CONCLUSIONS
Our data demonstrate an increase in both HMW adiponectin and total adiponectin in patients who had clinically recovered from sepsis. The increase in HMW/total adiponectin ratio with improvement of the clinical condition suggests that HMW adiponectin may have a greater role in the inflammatory process and insulin resistance seen in sepsis. In this pilot study, we have also demonstrated a significant increase in ZAG in critically ill patients temporally related to recovery from sepsis.

Welters|Ingeborg D|ID|
Bing|Chen|C|
Ding|Cherlyn|C|
Leuwer|Martin|M|
Hall|Alison M|AM|

Adipokines
Adiponectin
Zinc-α2-glycoprotein
Sepsis
HMW adiponectin


Factors that Influence the Immunological Adjuvant Effect of Lactobacillus fermentum PC1 on Specific Immune Responses in Mice to Orally Administered Antigens.

Abstract: This study examined the influences of the dosage of the adjuvant, the nature of the antigen and the host genetics on the capacity of L. fermentum PC1 (PC1) to function as an oral adjuvant. BALB/c and DBA/1 mice were vaccinated with either ovalbumin (OVA) or Salmonella Typhimurium on days 0 and 14, Mice were also dosed with the PC1 (10⁸ CFU or 10(11) CFU per dose per mouse) with the antigens (days 0 and 14) and alone (days -1 and 13). The higher PC1 dose elicited a greater specific serum IgG2a response than IgG1 for both antigens and mice strains, indicating a Th1-biased humoral immune response. The Th1 bias was also observed at the cellular level with greater specific IFN-γ levels than IL-4 and IL-10 with both antigen types and mouse strains. With the particulate antigen, the lower dose of PC1 elicited a Th1 bias at the cellular level, but a balanced Th1/Th2 response at the systemic humoral level. With the soluble antigen, a strong Th1-biased response occurred at the cellular level while the systemic humoral response was Th2-biased. In conclusion, PC1 at the higher dose was an excellent Th1 adjuvant, which was unaffected by the nature of the antigen or the host's genetic background.

adjuvant
lactobacillus
L. fermentum PC1
oral adjuvant
OVA
S. Typhimurium


Remote interviews for medical residency selection during the initial COVID-19 crisis: a national survey.

Abstract:
BACKGROUND
Medical training programs candidate's interview is an integral part of the residency matching process. During the coronavirus disease 2019 (COVID-19) pandemic, conducting these interviews was challenging due to infection prevention restrains (social distancing, namely) and travel restrictions. E-interviews were implemented by the Saudi Commission for Healthcare Specialties (SCFHS) since the matching cycle of March 2020 to hold the interviews in a safer virtual environment while maintaining the same matching quality and standards.

AIM
This study was conducted to assess the medical training residency program applicants' satisfaction, stress, and other perspectives for the (SCFHS) March 2020 Matching-cycle conducted through an urgently implemented E-interviews process.

METHOD
A cross-sectional, nationwide survey (Additional file 1) was sent to 4153 residency-nominated applicants to the (SCFHS) March 2020 cycle.

RESULTS
Among the 510 candidates who responded, 62.2% applied for medical specialties, 20.2% applied for surgical specialties, and 17.6% applied for critical care and emergency specialties. Most respondents (61.2%) never had previous experience with web-based video conferences. Most respondents (80.2%) used the Zoom application to conduct the current E-interviews, whereas only 15.9% used the FaceTime application. 63.3% of the respondents preferred E-interviews over in-person interviews, and 60.6% rated their experience as very good or excellent. 75.7% of the respondents agreed that all their residency program queries were adequately addressed during the E-interviews. At the same time, 52.2% of them agreed that E-interviews allowed them to represent themselves accurately. 28.2% felt no stress at all with their E-interviews experience, while 41.2% felt little stressed and only 8.2% felt highly stressed. The factors that were independently and inversely associated with applicants' level of stress with E-interviews experience were their ability to represent themselves during the interviews (p = 0.001), cost-savings (p < 0.001), their overall rating of the E-interviews quality (p = 0.007) and the speed of the internet connection (p < 0.006).

CONCLUSION
Videoconferencing was implemented on an urgent basis during the COVID-19 pandemic in the medical residency application process in Saudi Arabia. It was perceived as an adequate and promising tool to replace in-person interviews in the future. Applicants' satisfaction was mainly driven by good organization, cost-saving, and their ability to present themselves. Future studies to enhance this experience are warranted.

Medical residency
COVID-19
Survey
E-interviews
Satisfaction
Stress
Cost-saving


Cancer-Targeting Nanoparticles for Combinatorial Nucleic Acid Delivery.

Abstract: Nucleic acids are a promising type of therapeutic for the treatment of a wide range of conditions, including cancer, but they also pose many delivery challenges. For efficient and safe delivery to cancer cells, nucleic acids must generally be packaged into a vehicle, such as a nanoparticle, that will allow them to be taken up by the target cells and then released in the appropriate cellular compartment to function. As with other types of therapeutics, delivery vehicles for nucleic acids must also be designed to avoid unwanted side effects; thus, the ability of such carriers to target their cargo to cancer cells is crucial. Classes of nucleic acids, hurdles that must be overcome for effective intracellular delivery, types of nonviral nanomaterials used as delivery vehicles, and the different strategies that can be employed to target nucleic acid delivery specifically to tumor cells are discussed. Additonally, nanoparticle designs that facilitate multiplexed delivery of combinations of nucleic acids are reviewed.

nanoparticles
nucleic acid
cancer therapy
gene delivery
targeted delivery


Early postpartum biofeedback assisted pelvic floor muscle training in primiparous women with second degree perineal laceration: Effect on sexual function and lower urinary tract symptoms.

Abstract:
OBJECTIVE
To evaluate the short-term effect of routine early postpartum electromyographic biofeedback assisted pelvic floor muscle training on sexual function and lower urinary tract symptoms.

MATERIALS AND METHODS
From December 2016 to November 2017, primiparous women with vaginal delivery, who experienced non-extended second-degree perineal laceration were invited to participate. Seventy-five participants were assigned into a pelvic floor muscle training (PFMT) group or control group. Women in the PFMT group received supervised biofeedback-assisted pelvic floor muscle training at the 1st week and 4th week postpartum. Exercises were performed at home with the same protocol until 6 weeks postpartum. The Pelvic Organ Prolapse Urinary Incontinence Sexual Questionnaire (PISQ-12) and the Urinary Distress Inventory short form questionnaire (UDI-6) were used to evaluate sexual function and lower urinary tract symptoms respectively at immediate postpartum, 6 weeks, 3 months, and 6 months postpartum.

RESULTS
Forty-five women (23 in PFMT group,22 in control group) completed all questionnaires at 6 months postpartum. For overall sexual function and the three sexual functional domains, no statistically significant difference was found in PISQ scores from baseline to 6 weeks, 3 months, and 6 months postpartum between the PFMT and control groups. For postpartum lower urinary tract symptoms, all symptoms gradually improved over time for both groups without a statistically significant difference between groups.

CONCLUSION
Our study showed that supervised biofeedback-assisted pelvic floor muscle training started routinely at one week postpartum did not provide additional improvement in postpartum sexual function and lower urinary tract symptoms.

Wu|Ting-Feng|TF| Huang|Li-Hua|LH| Lai|Yu-Fen|YF| Chen|Gin-Den|GD| Ng|Soo-Cheen|SC|

Primiparous
Sexual function
Second-degree perineal laceration
Early intervention
Supervised pelvic floor muscle training


Light- and temperature-responsive liposomes incorporating cinnamoyl Pluronic F127.

Abstract: Light- and temperature-responsive liposomes were prepared by immobilizing cinnamoyl Pluronic F127 (CP F127) on the surface of egg phosphatidylcholine liposomes. CP F127 was prepared by a condensation reaction, and the molar ratio of cinnamoyl group to Pluronic F127 was calculated to be 1:1.4 on (1)H NMR spectrum. The cinnamoyl group of CP F127 was readily dimerized under the irradiation of a UV light (254 nm, 6 W). CP F127 decreased the absolute value of the zeta potential of liposome possibly because it can shift the hydrodynamic plane away from the liposome surface. The size of liposome decorated with CP F127, measured on a dynamic light scattering machine and observed on a TEM, was larger than that of bare liposome. The liposome bearing CP F127 seemed to fuse and aggregate each other. The liposome released calcein, a fluorescence dye, in response to a UV irradiation, possibly because the photo-dimerization of cinnamoyl group perturbs the liposomal membrane. Moreover, the liposome released the dye in response to a temperature change, possible due to the phase transition of Pluronic F127 layer on the liposomal surface or the hydrophobic interaction of the polymer with liposomal membrane.

D066244:Proton Magnetic Resonance Spectroscopy

Temperature-responsive
Liposomes
Cinnamoyl Pluronic F127
Release
Light-responsive


Abstract:
Aim
This pilot study evaluates the safety and efficacy of a novel surgical technique using fibrin glue to treat bleb dysesthesia post-trabeculectomy due to intrapalpebral extension.

Background
Trabeculectomy remains the gold standard for control of intraocular pressure (IOP) in refractory glaucoma. Bleb dysesthesia following antifibrotic-enhanced trabeculectomy is common, resulting in a significant decrease in quality of life. Symptoms include pain, foreign body sensation, and excessive tearing. Treatments include lubrication, topical nonsteroidal anti-inflammatory drugs (NSAIDs), bandage contact lens, bleb needling, compression sutures, Nd:YAG laser treatments, autologous blood injection, and cryopexy. These procedures can be time-consuming, risk bleb function, and may be ineffective at symptom control; thus, a novel technique is required.

Technique
This is a retrospective case series of eyes undergoing bleb dissection with scleral cutdown and conjunctival closure with ARTISS fibrin tissue glue. Reported cases have been followed up for 6 months. Outcomes assessed include complications, IOP, medication usage, subjective pain score, visual field, and cup-to-disk (C:D) ratio.

Conclusion
This small pilot series demonstrated that patients suffering from bleb dysesthesia due to intrapalpebral bleb extension can be successfully treated with a novel surgical approach combining conjunctival dissection to sclera with fibrin tissue glue closure. There was no significant effect on bleb function and no contribution to glaucoma progression over a 6-month period. A significant reduction in patient discomfort with no new surgical complications was noted.

Clinical significance
This demonstrates a safe and effective novel surgical approach to treat patients with this condition. The technique is easily learnt and can be employed in an outpatient setting. The technique is readily accepted by patients in group who are often reticent to undergo further intervention. Most importantly, it does not compromise bleb function or destabilize glaucoma control.

How to cite this article
Holmes DP, Manning DK. Intrapalpebral Extending Dysesthetic Bleb Revision with Fibrin Glue. J Curr Glaucoma Pract 2020;14(1):37-42.

Bleb
Fibrin glue
Surgical technique
Dysesthesia
Trabeculectomy
Intraocular pressure
Glaucoma


Real-Time Detection and Control of Microchannel Resonance Frequency in Acoustic Trapping Systems by Monitoring Amplifier Supply Currents.

Abstract: The utilization of bulk acoustic waves from a piezoelectric transducer for selective particle trapping under flow in a microchannel is limited by the high sensitivity of the resonance frequency to tolerances in device geometry, drift during trapping, and variations in the local flow or sample conditions in each channel. This is addressed by detecting the resonance condition based on the impedance minimum obtained by monitoring the amplitude of the stimulation voltage across the piezo transducer and utilizing real-time feedback to control the stimulation frequency. However, this requires an overlap in the frequency bandwidth of the detection and the stimulation system and is also limited by the decline in the acoustic trapping power when the stimulation and resonance frequency measurement are conducted simultaneously. Instead, we present a novel circuit implementation for on-chip real-time resonance frequency measurement and feedback control based on monitoring the current drawn from the amplifier used to stimulate the piezo transducer, since the need for high measurement sensitivity in this mode does not lower the power available for stimulation of the transducer. The enhanced level of control of acoustic trapping utilizing this current mode is validated for various localized channel perturbations, including drift, wash steps, and buffer swaps, as well as for selective sperm cell trapping from a heterogeneous sample that includes lysed epithelial cells.

Farmehini|Vahid|V|
Kiendzior|Sadie|S|
Landers|James P|JP|
Swami|Nathan S|NS|0000-0002-0492-1160

sperm cells
acoustophoresis
microfluidics
multiplexed control systems
sensor integration


One-pot synthesis of magnetic iron oxide nanoparticle-multiwalled carbon nanotube composites for enhanced removal of Cr(VI) from aqueous solution.

Abstract: Magnetic nanoparticle-multiwalled carbon nanotubes composites (MNP/MWCNTs) were prepared using 1,6-hexanediamine functionalized Fe3O4 nanoparticles (MNP) linked to carboxylic MWCNTs by facile one-pot solvothermal synthesis for highly efficient removal of Cr(VI) from aqueous solution. The easily obtained magnetic nanocomposites were systematically characterized, and several major factors affecting the adsorption-based removal were investigated, including solution pH, adsorbent dosage, temperature and contact time. The removal efficiency was highly dependent on solution pH; low pH facilitated removal with the maximum efficiency at pH 2.0. The adsorption isotherm was well fitted with the Langmuir isotherm model and the adsorption capacity increased with the temperature increasing. The adsorption kinetic data could be well described by the pseudo-second-order and the intraparticle diffusion models, indicating that the intraparticle diffusion was not the only rate-limiting step. The MNP/MWCNTs displayed excellent selectivity and high anti-interference ability toward Cr(VI) when confronted with commonly coexisting ions. By using an external magnetic field, the exhausted MNP/MWCNTs could be readily separated from the solution after adsorption of Cr(VI) and well regenerated, and could keep about 80% removal efficiency in the fifth adsorption-desorption cycle. The simple, rapid and reliable MNP/MWCNT-based method proved to be a cost-effective, convenient and potentially applicable way to targeted pollutant removal and wastewater treatment.

Lu|Wenhui|W| Li|Jinhua|J| Sheng|Yanqing|Y| Zhang|Xinshen|X| You|Jinmao|J| Chen|Lingxin|L|

Removal
Cr(VI)
Nanocomposites
Adsorption
Magnetic separation
Multiwalled carbon nanotubes


Temporomandibular joint vibrations from totally asymptomatic subjects.

Abstract:
OBJECTIVE
Precisely characterize the TMJ vibrations of a youthful, adult and completely asymptomatic population.

METHODS
TMJ vibrations were recorded from 237 asymptomatic subjects (163 f, 74 m) at Dayananda Sagar Institute in India. The subjects were selected, examined and informed (WMA Helsinki Declaration). TMJ vibrations were recorded bilaterally during maximal open - close. 6 parameters of the vibrations were analyzed between the left and right sides, between genders and with respect to age.

RESULTS
Mean vibration intensity was greater for females (p < 0.01) than males. A portion of the frequency spectrum < 300 Hz was also more intense for females (p < 0.022). Females 18 - 20 years old exhibited higher Peak Amplitude than 27 - 30 year olds (p < 0.025) and lower Median Frequency (p < 0.005).

CONCLUSIONS
A significant difference in TMJ vibrations was present between males and females, increased with age in females but not in males.

Peak amplitude
Median frequency
Frequency distribution
Joint vibration analysis
Total integral


New distributional and bioacoustic data about Cicadivetta goumenissa from Peloponnese, Greece (Hemiptera, Cicadidae).

Abstract: Cicadivetta goumenissa, a small singing cicada described recently by Gogala et al. (2012), has been previously found only around the village of Goumenissa in northern Peloponnese. We visited this area again in June 2012 and tried to determine the distribution range of this species. We found Cicadivetta goumenissa in some further localities, but all within a very small area of about 15 by 25 km. We also made more than one hour of new song recordings and extended our knowledge of the song repertoire of this species.

Cicadivetta goumenissa
Hemiptera
Cicadidae
geographical distribution
song pattern


Comparison between National Institute for Health and Care Excellence (NICE) and European Society of Cardiology (ESC) guidelines for the diagnosis and management of stable angina: implications for clinical practice.

Abstract: Cardiologists in the UK use clinical practice guidelines from the National Institute for Health and Care Excellence (NICE) and from the European Society of Cardiology (ESC) to aid clinical decision-making. This review compares their recommendations regarding stable angina. NICE's diagnostic algorithm changed clinical practice in the UK, with most cardiologists moving from the exercise ECG towards newer, more accurate imaging modalities such as CT and MRI for diagnostic testing in patients with a low or medium probability of coronary artery disease (CAD), and directly to invasive coronary angiography in patients with a high probability of CAD. ESC guidelines are based around stress imaging for most patient groups. Both guidelines stress the importance of optimal medical therapy for patients with stable angina. NICE recommends coronary artery bypass graft surgery to improve prognosis for patients with left main stem and/or proximal 3-vessel disease, whereas the ESC also includes proximal left anterior descending artery disease among its indications for revascularisation to improve prognosis, particularly if there is evidence of myocardial ischaemia. The relation between disease complexity and 5-year clinical outcomes after revascularisation in patients with left main stem and/or 3-vessel CAD has been integrated into ESC guidance through the use of the SYNTAX score to aid treatment selection in this group of patients. Patients with stable angina who have disease involving the proximal left anterior descending artery are less likely to undergo myocardial revascularisation if they are managed according to NICE's guidance compared with the ESC's guidance.


Let-7 microRNA as a potential therapeutic target with implications for immunotherapy.

Abstract: MicroRNAs (miRNA) are a class of small non-coding RNA that play a major role in various cellular processes by negatively regulating gene expression. In the past decade, miRNA dysregulation has been reported to be closely linked to inflammatory diseases. The immune response modulates cancer initiation and progression; miRNAs including let-7 family members have been shown to act as key regulators of the immune responses in various diseases and cancers. Notably, the let-7 miRNA has been reported to be closely associated with immunity, specifically with Toll-like receptors that mediate cytokine expression during pathogen infection and with the regulation of various other immune effectors. Areas covered: In this review, the authors describe the discovery of let-7 as the starting point of the RNA revolution and highlight let-7 as an efficient tool for cancer and immune therapy. Expert opinion: let-7 miRNA has emerged as a key player in cancer therapy and immune responses and it has potential role as a new immunotherapeutic target. However, while there are challenges regarding miRNA delivery, the exciting emergence of personalized medicine for cancer and immunotherapy could be beneficial for the development of let-7 therapeutics.

let-7
immunotherapy
miRNAs
immune response
RNA therapy


A pediatric case of T-cell prolymphocytic leukemia.

Abstract: T-cell Prolymphocytic Leukemia (T-PLL) is a rare entity, and to date has never been reported in children. Here, we describe the first pediatric case of T-PLL in a 16-year old male and review his clinical course through treatment. He underwent therapy with alemtuzumab and pentostatin, which was successful in inducing initial remission. He then underwent an allogeneic matched sibling stem cell transplant following a myeloablative conditioning regimen and remains disease-free 1.5 years after diagnosis.

Mitton|Bryan|B| Coutre|Steven|S| Willert|Jennifer|J| Schlis|Krysta|K| Porteus|Matthew|M| Kharbanda|Sandhya|S| Agarwal-Hashmi|Rajni|R|

D018380:Hematopoietic Stem Cell Transplantation

pediatrics
T-cell prolymphocytic leukemia
bone marrow transplant


miRNA-4317 suppresses human gastric cancer cell proliferation by targeting ZNF322.

Abstract: Studies have shown that miR-4317 is dysregulated in tumor, but the biologic role of miR-4317 in tumor development and progression remains unknown. The present study aimed to investigate the role of miR-4317 in human gastric cancer. Quantitative real-time PCR was used to quantify miR-4317 expression levels in clinical gastric cancer specimens and cell lines. MTT, colony formation and cell cycle assays were performed to identify the contributions of miR-4317 to cell proliferation in gastric cancer cell lines. The results showed that miR-4317 was significantly decreased in 17 clinical gastric cancer specimens compared with adjacent non-tumor stomach tissues. Forced expression of miR-4317 suppressed gastric cancer cell proliferation and blocked S-G2/M transition. Bioinformatics and dual-luciferase reporter assays confirmed that ZNF322 is a direct target of miR-4317. Silencing ZNF322 recapitulated the cellular and molecular effects seen upon miR-4317 overexpression. These findings indicate that miR-4317 represses the proliferation of gastric cancer cell, at least in part, by targeting and suppressing ZNF322 and that it may serve as a therapeutic target for gastric cancer treatment.


Renal transplantation in HIV patients: A series of four cases.

Abstract: Human immunodeficiency virus (HIV) infection in a patient with end-stage renal disease was considered a contraindication for renal transplantation till now despite the advent of highly active antiretroviral therapy with the apprehension that immunosuppression would further jeopardize the already compromised immune status of the patients. Renal transplantation in HIV patients is rare in developing countries including ours. Here we report a series of four cases of renal transplantation in HIV patients.

Agarwal|D K|DK|
Hota|J K|JK|
Nag|N|N|
Mehta|S N|SN|

human immunodeficiency virus
End-stage renal disease
highly active antiretroviral therapy
immunosuppression


Apatinib exerts anti-tumour effects on ovarian cancer cells.

Abstract:
OBJECTIVE
Apatinib, a small molecule inhibitor of VEGFR-2 tyrosine kinase, shows strong anti-tumour activity against various tumours. The function of apatinib in ovarian cancer, however, remains unclear. This study was conducted to investigate the effects and potential mechanisms by which apatinib modulates the biological function of ovarian cancer cells in vitro and in vivo.

METHODS
The effects of apatinib on ovarian cancer cells were determined by assessing cell viability, migration and invasion. The cell cycle distribution and apoptosis of ovarian cancer cells were analysed using flow cytometry. Western blotting was performed to determine the levels of signalling pathway markers. A mouse xenograft model was used to evaluate the efficacy of apatinib in preventing tumour growth.

RESULTS
Apatinib did not appreciably affect ovarian cancer cell proliferation and vitality, but did inhibit ovarian cancer cell migration. Apatinib suppressed the epithelial-mesenchymal transition in ovarian cancer cells by inhibiting the JAK/STAT3, PI3K/AKT and Notch signalling pathways. Apatinib effectively inhibited tumour growth in vivo.

CONCLUSION
Based on our findings, apatinib is a highly potent, orally active anti-angiogenic and anti-ovarian cancer agent.

Ding|Jing|J| Cheng|Xiao-Yan|XY| Liu|Shuang|S| Ji|Hong-Ying|HY| Lin|Mu|M| Ma|Rong|R| Meng|Fan-Ling|FL|

D023041:Xenograft Model Antitumor Assays

Apatinib
Ovarian cancer
Signalling pathway
Cell migration
Epithelial-mesenchymal transition