The use of contact lenses in low vision rehabilitation: optical and therapeutic applications.

Abstract: Ocular pathology that manifests at an early age has the potential to alter the vision-dependent emmetropisation mechanism, which co-ordinates ocular growth throughout childhood. The disruption of this feedback mechanism in children with congenital or early-onset visual impairment often results in the development of significant ametropia, including high levels of spherical refractive error, astigmatism and anisometropia. This review examines the use of contact lenses as a refractive correction, low vision aid and therapeutic intervention in the rehabilitation of patients with bilateral, irreversible visual loss due to congenital ocular disease. The advantages and disadvantages of the use of contact lenses for increased magnification (telescopes and microscopes) or field expansion (reverse telescopes) are discussed, along with the benefits and practical considerations for the correction of pathological high myopia. The historical and present use of therapeutic tinted contact lenses to reduce photosensitivity and nystagmus in achromatopsia, albinism and aniridia are also presented, including clinical considerations for the contact lens practitioner. In addition to the known optical benefits in comparison to spectacles for high levels of ametropia (an improved field of view for myopes and fewer inherent oblique aberrations), contact lenses may be of significant psycho-social benefit for patients with low vision, due to enhanced cosmesis and reduced conspicuity and potential related effects of improved self-esteem and peer acceptance. The contact lens correction of patients with congenital vision impairment can be challenging for both practitioner and patient but should be considered as a potential optical or therapeutic solution in modern low vision rehabilitation.

D003261:Contact Lenses
D006801:Humans
D055095:Optics and Photonics
D012030:Refractive Errors
D015354:Vision, Low


Fiber Reinforced Compressed Earth Blocks: Evaluating Flexural Strength Characteristics Using Short Flexural Beams.

Abstract: There are ongoing research efforts directed at addressing strength limitations of compressed earth blocks (CEB) that inhibit their deployment for structural applications, particularly in areas where masonry systems are regularly subjected to lateral loads from high winds. In this paper, the authors focus specifically on the extent to which polypropylene (PP) fibers can be used to enhance the flexural performance of CEB. Cementitious matrices used for CEB production exhibit low tensile and flexural strength (brittle) properties. This work investigates plain (unreinforced) and fiber-reinforced specimens (short flexural beams) with fiber mass content of 0.2, 0.4, 0.6, 0.8, and 1.0% and ordinary Portland cement (OPC) content of 8%. The influence of the inclusion of fiber was based on tests conducted using the Standard Test Method for Flexural Performance of Fiber-Reinforced Concrete (ASTM C1609). Material properties that were quantified included first-peak strength, peak strength, equivalent flexural strength, residual strength, and flexural toughness. There was an observed improvement in the performance of the soil-fiber matrixes based on these results of these tests. It was also observed that when the fiber content exceeded 0.6% and above, specimens exhibited a deflection- hardening behavior; an indication of improvement in ductility. An equivalent flexural strength predictive model is proposed.

compressed earth blocks
equivalent flexural strength
residual strength
flexural toughness
polypropylene fibers


Altered Plasma Profile of Antioxidant Proteins as an Early Correlate of Pancreatic β Cell Dysfunction.

Abstract: Insulin resistance and β cell dysfunction contribute to the pathogenesis of type 2 diabetes. Unlike insulin resistance, β cell dysfunction remains difficult to predict and monitor, because of the inaccessibility of the endocrine pancreas, the integrated relationship with insulin sensitivity, and the paracrine effects of incretins. The goal of our study was to survey the plasma response to a metabolic challenge in order to identify factors predictive of β cell dysfunction. To this end, we combined (i) the power of unbiased iTRAQ (isobaric tag for relative and absolute quantification) mass spectrometry with (ii) direct sampling of the portal vein following an intravenous glucose/arginine challenge (IVGATT) in (iii) mice with a genetic β cell defect. By so doing, we excluded the effects of peripheral insulin sensitivity as well as those of incretins on β cells, and focused on the first phase of insulin secretion to capture the early pathophysiology of β cell dysfunction. We compared plasma protein profiles with ex vivo islet secretome and transcriptome analyses. We detected changes to 418 plasma proteins in vivo, and detected changes to 262 proteins ex vivo The impairment of insulin secretion was associated with greater overall changes in the plasma response to IVGATT, possibly reflecting metabolic instability. Reduced levels of proteins regulating redox state and neuronal stress markers, as well as increased levels of coagulation factors, antedated the loss of insulin secretion in diabetic mice. These results suggest that a reduced complement of antioxidants in response to a mixed secretagogue challenge is an early correlate of future β cell failure.

Kuo|Taiyi|T|
Kim-Muller|Ja Young|JY|
McGraw|Timothy E|TE|
Accili|Domenico|D|

diabetes
FOXO
beta cell (B-cell)
biomarker
neurodegeneration
oxidative stress


Loss of Arabidopsis β-COP Function Affects Golgi Structure, Plant Growth and Tolerance to Salt Stress.

Abstract: The early secretory pathway involves bidirectional transport between the endoplasmic reticulum (ER) and the Golgi apparatus and is mediated by coat protein complex I (COPI)-coated and coat protein complex II (COPII)-coated vesicles. COPII vesicles are involved in ER to Golgi transport meanwhile COPI vesicles mediate intra-Golgi transport and retrograde transport from the Golgi apparatus to the ER. The key component of COPI vesicles is the coatomer complex, that is composed of seven subunits (α/β/β'/γ/δ/ε/ζ). In Arabidopsis two genes coding for the β-COP subunit have been identified, which are the result of recent tandem duplication. Here we have used a loss-of-function approach to study the function of β-COP. The results we have obtained suggest that β-COP is required for plant growth and salt tolerance. In addition, β-COP function seems to be required for maintaining the structure of the Golgi apparatus.

Sánchez-Simarro|Judit|J|
Bernat-Silvestre|César|C|
Gimeno-Ferrer|Fátima|F|
Selvi-Martínez|Pilar|P|
Montero-Pau|Javier|J|
Aniento|Fernando|F|
Marcote|María Jesús|MJ|

Arabidopsis
β-COP
plant growth
salt stress
Golgi apparatus
coat protein I (COPI)
coat protein II (COPII)


Deep bleeder acoustic coagulation (DBAC)-Part I: development and in vitro testing of a research prototype cuff system.

Abstract:
BACKGROUND
Bleeding from limb injuries is a leading cause of death on the battlefield, with deep wounds being least accessible. High-intensity focused ultrasound (HIFU) has been shown capable of coagulation of bleeding (cautery). This paper describes the development and refereed in vitro evaluation of an ultrasound (US) research prototype deep bleeder acoustic coagulation (DBAC) cuff system for evaluating the potential of DBAC in the battlefield. The device had to meet quantitative performance metrics on automated operation, therapeutic heating, bleeder detection, targeting accuracy, operational time limits, and cuff weight over a range of limb sizes and bleeder depths. These metrics drove innovative approaches in image segmentation, bleeder detection, therapy transducers, beam targeting, and dose monitoring. A companion (Part II) paper discusses the in vivo performance testing of an animal-specific DBAC system.

MATERIALS AND METHODS
The cuff system employed 3D US imaging probes ("Ix") for detection and localization (D&L) and targeting, with the bleeders being identified by automated spectral Doppler analysis of flow waveforms. Unique high-element-count therapeutic arrays ("Tx") were developed, with the final cuff prototype having 21 Tx's and 6 Ix's. Spatial registration of Ix's and Tx's was done with a combination of image-registration, acoustic time-of-flight measurement, and tracking of the cuff shape via a fiber optic sensor. Acoustic radiation force impulse (ARFI) imaging or thermal strain imaging (TSI) at low-power doses were used to track the HIFU foci in closed-loop targeting. Recurrent neural network (RNN) acoustic thermometry guided closed-loop dosing. The cuff was tested on three phantom "limb" sizes: diameters = 25, 15, and 7.5 cm, with bleeder depths from 3.75 to 12.5 cm. "Integrated Phantoms" (IntP) were used for assessing D&L, closed-loop targeting, and closed-loop dosing. IntPs had surrogate arteries and bleeders, with blood-mimicking fluids moved by a pulsatile pump, and thermocouples (TCs) on the bleeders. Acoustic dosing was developed and tested using "HIFU Phantoms" having precisely located TCs, with end-of-dose target ∆T = 33-58 °C, and skin temperature ∆T ≤ 20 °C, being required.

RESULTS
Most DBAC cuff performance requirements were met, including cuff weight, power delivery, targeting accuracy, skin temperature limit, and autonomous operation. The automated D&L completed in 9 of 15 tests (65 %), detecting the smallest (0.6 mm) bleeders, but it had difficulty with the lowest flow (3 cm/sec) bleeders, and in localizing bleeders in the smallest (7.5 cm) phantoms. D&L did not complete within the 9-min limit (results ranged 10-21 min). Closed-loop targeting converged in 20 of 31 tests (71 %), and closed-loop dosing power shut-off at preset ∆Ts was operational.

SUMMARY AND CONCLUSION
The main performance objectives of the prototype DBAC cuff were met, however the designs required a number of challenging new technology developments. The novel Tx arrays exhibited high power with significant beam steering and focusing flexibility, while their integrated electronics enabled the required compact, lightweight configurability and simplified driving controls and cable/connector architecture. The compounded 3D imaging, combined with sophisticated software algorithms, enabled automated D&L and initial targeting and closed-loop targeting feedback via TSI. The development of RNN acoustic thermometry made possible feedback-controlled dosing. The lightweight architecture required significant design and fabrication effort to meet mechanical functionalities. Although not all target specifications were met, future engineering solutions addressing these performance deficiencies are proposed. Lastly, the program required very complex limb test phantoms and, while very challenging to develop, they performed well.

Sekins|K Michael|KM|
Barnes|Stephen R|SR|
Fan|Liexiang|L|
Hopple|Jerry D|JD|
Hsu|Stephen J|SJ|
Kook|John|J|
Lee|Chi-Yin|CY|
Maleke|Caroline|C|
Ramachandran|A R|AR|
Zeng|Xiaozheng Jenny|XJ|
Moreau-Gobard|Romain|R|
Ahiekpor-Dravi|Alexis|A|
Funka-Lea|Gareth|G|
Mitchell|Stuart B|SB|
Dunmire|Barbrina|B|
Kucewicz|John C|JC|
Eaton|John|J|
Wong|Keith|K|
Keneman|Scott|S|
Crum|Lawrence A|LA|

Acoustic coagulation
Bleeding
Ultrasound
HIFU
Cautery
ARFI
Recurrent neural network
Neural network
Acoustic thermometry
Phantom
Acoustic hemostasis
Combat bleeding
Image compounding


Medication Adherence, Health Care Utilization, and Costs in Patients With Major Depressive Disorder Initiating Adjunctive Atypical Antipsychotic Treatment.

Abstract:
PURPOSE
The purpose of this study was to compare medication adherence, health care utilization, and cost among patients receiving adjunctive treatment for major depressive disorder (MDD) with brexpiprazole, quetiapine, or lurasidone.

METHODS
Using Truven Health MarketScan® Commercial, Medicaid, and Medicare Supplemental Databases, we identified adults with MDD initiating adjunctive treatment with brexpiprazole, quetiapine, or lurasidone (index atypical antipsychotic [AAP]). We compared medication adherence and persistence measured by proportion of days covered (PDC) and treatment duration of index AAP, all-cause and psychiatric hospital care (hospitalization or emergency department visit), and medical costs during 6-month follow-up. Models performed included logistic regression for hospital care, linear regression for PDC and cost, and Cox proportional hazards regression for time to discontinuation, adjusting for demographic, clinical, and utilization differences during the 6 months before index AAP.

FINDINGS
The total sample included 778 brexpiprazole, 626 lurasidone, and 3458 quetiapine therapy initiators. Adjusting for baseline differences, the risk of discontinuation of index AAP was statistically significantly higher for quetiapine than for brexpiprazole (hazard ratio [HR] = 1.13; 95% CI, 1.02-1.25; P = 0.023) and did not differ between lurasidone and brexipiprazole (HR = 1.14; 95% CI, 1.00-1.29; P = 0.054). The adjusted rate of all-cause hospitalization or emergency department visit in the postindex period was lowest for brexpiprazole at 27.4% (95% CI, 24.0%-31.0%), compared with 31.1% (95% CI, 27.3%-35.2%) for lurasidone and 35.3% (95% CI, 33.5%-37.1%) for quetiapine (P< 0.001 for all comparisons). Quetiapine users had increased all-cause costs compared with brexpiprazole users (estimate = $2309; 95% CI, $31-$4587; P = 0.047); all-cause medical costs did not differ between lurasidone and brexpiprazole (estimate = $913; 95% CI, $-2033 -$3859; P = 0.543). Adjusted psychiatric hospital care, psychiatric costs, and PDC did not differ significantly among the groups.

IMPLICATIONS
In patients with MDD and a variety of insurance types, brexpiprazole use was associated with statistically significantly lower risks of discontinuation, risk of hospital care (hospitalization and ED visits), and all-cause medical costs compared with adjunctive quetiapine. Differences between brexpiprazole and lurasidone were not statistically significant. These findings suggest that drug choice is associated with subsequent health care utilization and costs.

Broder|Michael S|MS|
Greene|Mallik|M|
Yan|Tingjian|T|
Chang|Eunice|E|
Hartry|Ann|A|
Yermilov|Irina|I|

D010342:Patient Acceptance of Health Care

medication adherence
health care utilization
costs
major depressive disorder
atypical antipsychotic
secondary data analysis


MicroRNA Dysregulation, Gene Networks, and Risk for Schizophrenia in 22q11.2 Deletion Syndrome.

Abstract: The role of microRNAs (miRNAs) in the etiology of schizophrenia is increasingly recognized. Microdeletions at chromosome 22q11.2 are recurrent structural variants that impart a high risk for schizophrenia and are found in up to 1% of all patients with schizophrenia. The 22q11.2 deletion region overlaps gene DGCR8, encoding a subunit of the miRNA microprocessor complex. We identified miRNAs overlapped by the 22q11.2 microdeletion and for the first time investigated their predicted target genes, and those implicated by DGCR8, to identify targets that may be involved in the risk for schizophrenia. The 22q11.2 region encompasses seven validated or putative miRNA genes. Employing two standard prediction tools, we generated sets of predicted target genes. Functional enrichment profiles of the 22q11.2 region miRNA target genes suggested a role in neuronal processes and broader developmental pathways. We then constructed a protein interaction network of schizophrenia candidate genes and interaction partners relevant to brain function, independent of the 22q11.2 region miRNA mechanisms. We found that the predicted gene targets of the 22q11.2 deletion miRNAs, and targets of the genome-wide miRNAs predicted to be dysregulated by DGCR8 hemizygosity, were significantly represented in this schizophrenia network. The findings provide new insights into the pathway from 22q11.2 deletion to expression of schizophrenia, and suggest that hemizygosity of the 22q11.2 region may have downstream effects implicating genes elsewhere in the genome that are relevant to the general schizophrenia population. These data also provide further support for the notion that robust genetic findings in schizophrenia may converge on a reasonable number of final pathways.

Merico|Daniele|D|
Costain|Gregory|G|
Butcher|Nancy J|NJ|
Warnica|William|W|
Ogura|Lucas|L|
Alfred|Simon E|SE|
Brzustowicz|Linda M|LM|
Bassett|Anne S|AS|

schizophrenia
22q11.2
miRNA
DGCR8
protein interaction network
22q11 deletion
DiGeorge syndrome
synapse


Anticonvulsant activity of methanolic extract from Kalanchoe pinnata Lam. stems and roots in mice: A comparison to diazepam.

Abstract:
INTRODUCTION
In ancient and current traditional medicine in México, extracts from the leaves or whole plant of 'life leaf' (Kalanchoe pinnata [K. pinnata]Lam) have been used to treat an entity known locally as 'yellow epilepsy' (alferecía amarilla) when it is accompanied by seizures. However, the anticonvulsive activity of its stems and roots remains unexplored

METHODS
The anticonvulsant activity of the methanolic root extract (MER) or stem (MES) of K. pinnata Lam. was evaluated in a pentylenetetrazol-induced seizure model in Balb/C mice, and effects were compared to those of diazepam. The stem extract fractions that produced anticonvulsant activity were subsequently evaluated using the pentylenetetrazol -induced seizure model.

RESULTS
We observed increased latency of tonic-clonic seizures that was inversely proportional to the dose of MRE, with a similar impact on the lethal effects of pentylenetetrazol. Different doses of the MSE showed a dose-dependent increase in latency to myoclonus, clonus, and tonic-clonic seizures, acting similarly to diazepam and offering 100% protection against the lethal effects of pentylenetetrazol. Fractioning MSE decreased its effectiveness, but when fractions were mixed with fractions of chloroform and ethyl acetate, anticonvulsive activity was restored. The preliminary phytochemical analysis identified alkaloids and sterols in MRE, and sterols and terpenes in MSE CONCLUSIONS: The anticonvulsant activity of K. pinnata Lam. decreases with increased doses of MRE, whereas the effect of MSE is dose-dependent and preserved in the mixture chloroform and ethyl acetate. We suggest that the metabolites responsible for these effects are sterols in MRE, and sterols and terpenes in MSE.

Mora-Pérez|A|A|
Hernández-Medel|M del R|Mdel R|

Anticonvulsant
Kalanchoe pinnata
Diazepam
Pentylenetetrazol
Anticonvulsivante
Bryophyllum pinnatum
Convulsiones
Convulsions
Pentilenetetrazol


Quality Control of DNA Extracted from All-Cell Pellets After Cryopreservation for More Than 10 Years.

Abstract: Cryopreserved whole blood, all-cell pellets (ACPs), and buffy coats in biobanks are widely used to obtain DNA for genetic testing. However, there are few studies concerning the quality control of DNA extracted from them. Our research aimed to perform quality control of DNA extracted from ACPs after cryopreservation for >10 years.  A total of 1377 ACP samples (separated from 3 mL of whole blood) were retrieved from our biobank, where they had been cryopreserved for 10-15 years. Chemagic STAR was used to extract the DNA. Absorbance at A260, A280, and A230 were measured by spectrophotometry, and integrity was analyzed by agarose gel electrophoresis. The quality thresholds for an Illumina Asian Screening Array (ASA) were yields greater than 0.5 μg, concentration of 25-150 ng/μL, A260/280 ratio of 1.6-2.1, and no degradation fragments in the electrophoresis gel.  The median yield of genomic DNA was 54.30 μg (interquartile range [IQR] 35.55-74.64). The median A260/280 and A260/230 ratios were 1.90 (IQR 1.87-1.94) and 1.98 (IQR 1.64-2.41), respectively. In total, 1377 samples (100%) had qualified yields, and 1366 samples (99.20%) had qualified integrity results. Finally, 1328 (96.44%) samples were used for ASA. Of the remaining samples, 34 needed to be repurified, 4 were obtained at an insufficient concentration, and 11 were unqualified for integrity. In addition, we analyzed the influence of hemolysis (90 samples) and clots (102 samples) on the quality of DNA samples. Hemolysis and clotting did not influence yield or integrity, but a significant difference was found in A260/230 compared to normal samples (p < 0.05). Furthermore, the samples (14 samples) with both hemolysis and clots had higher A260/280 (p < 0.05).  ACP samples stored for >10 years at -80°C produced DNA with high quality for use in genetic analysis. Hemolysis and clots in the ACPs led to lower purity, but did not significantly affect yield or integrity.


Effect of onion peel extract supplementation on the lipid profile and antioxidative status of healthy young women: a randomized, placebo-controlled, double-blind, crossover trial.

Abstract: The consumption of fruits and vegetables that have high polyphenol content has been previously associated with a reduced risk for cardiovascular disease. We investigated the effects of onion peel extract on plasma total antioxidant capacity, lipid peroxidation, and leukocyte DNA damage. This study was a randomized, double-blind, placebo-controlled, crossover trial. Healthy female subjects received either onion peel extract or placebo (dextrin) for two weeks, underwent a 1-week washout period, and then received the other treatment for an additional two weeks. After two weeks of onion peel extract supplementation, the total cholesterol level, low-density lipoprotein cholesterol level, and atherogenic index significantly decreased (P < 0.05). No changes were observed in activities of erythrocyte antioxidant enzymes or levels of lipid peroxidation markers following onion peel extract supplementation. Additionally, no significant difference was found in plasma antioxidant vitamin (retinol, tocopherols, carotenoids, and coenzyme Q10) levels or ex vivo H2O2-provoked oxidative DNA damage after onion peel extract supplementation. The present interventional study provides evidence of the health benefits of onion peel extract and demonstrates its effects in modulating lipid profiles in healthy young Korean women.

Kim|Jungmi|J| Cha|Yong-Jun|YJ| Lee|Kyung-Hea|KH| Park|Eunju|E|

Onion peel extract
lipid profile
antioxidant status
healthy young women
DNA damage


Patient Demographics and Clinic Type Are Associated With Patient Engagement Within a Remote Monitoring Program.

Abstract: Background: Remote physiological monitoring (RPM) is accessible, convenient, relatively inexpensive, and can improve clinical outcomes. Yet, it is unclear in which clinical setting or target population RPM is maximally effective. Objective: To determine whether patients' demographic characteristics or clinical settings are associated with data transmission and engagement. Methods: This is a prospective cohort study of adults enrolled in a diabetes RPM program for a minimum of 12 months as of April 2020. We developed a multivariable logistic regression model for engagement with age, gender, race, income, and primary care clinic type as variables and a second model to include first-order interactions for all demographic variables by time. The participants included 549 adults (mean age 53 years, 63% female, 54% Black, and 75% very low income) with baseline hemoglobin A1c ≥8.0% and enrolled in a statewide diabetes RPM program. The main measure was the transmission engagement over time, where engagement is defined as a minimum of three distinct days per week in which remote data are transmitted. Results: Significant predictors of transmission engagement included increasing age, academic clinic type, higher annual household income, and shorter time-in-program (p < 0.001 for each). Self-identified race and gender were not significantly associated with transmission engagement (p = 0.729 and 0.237, respectively). Conclusions: RPM appears to be an accessible tool for minority racial groups and for the aging population, yet engagement is impacted by primary care location setting and socioeconomic status. These results should inform implementation of future RPM studies, guide advocacy efforts, and highlight the need to focus efforts on maintaining engagement over time.

remote monitoring
primary care
health disparities
telemedicine
underserved populations


Missions, Humanitarianism, and the Evolution of Modern Global Surgery.

Abstract: Modern global surgery, which aims to provide improved and equitable surgical care worldwide, is a product of centuries of international care initiatives, some borne out of religious traditions, dating back to the first millennium. The first hospitals (xenodochia) were established in the 4th and 5th centuries CE by the early Christian church. Early "missions," a term introduced by Jesuit Christians in the 16th century to refer to the institutionalized expansion of faith, included medical care. Formalized Muslim humanitarian medical care was marked by organizations like the Aga Khan Foundation and the Islamic Association of North America in the 20th century. Secular medical humanitarian programs developed in the 19th century, notably with the creation of the International Committee of the Red Cross (1863) and the League of Nations Health Organization (1920) (which later became the World Health Organization [1946]). World War II catalyzed another proliferation of nongovernmental organizations, epitomized by the quintessential humanitarian health provider, Médecins Sans Frontières (1971). "Global health" as an academic endeavor encompassing education, service, and research began as an outgrowth of departments of tropical medicine and international health. The American College of Surgeons brought a surgical focus to global health beginning in the 1980s. Providing medical care in distant countries has a long tradition that parallels broad themes in history: faith, imperialism, humanitarianism, education, and service. Surgery as a focus of academic global health is a recent development that continues to gain traction.

Ellis|Danielle I|DI|
Nakayama|Don K|DK|
Fitzgerald|Tamara N|TN|

D000533:Altruism
D003906:Developing Countries
D014943:Global Health
D049669:History, 16th Century
D049670:History, 17th Century
D049671:History, 18th Century
D049672:History, 19th Century
D049673:History, 20th Century
D049674:History, 21st Century
D049690:History, Ancient
D049691:History, Medieval
D006801:Humans
D008493:Medical Missions
D008921:Religious Missions
D013043:Specialties, Surgical

global Surgery
history
faith-based organization
humanitarian missions


Porous microspheres of polyaniline, poly(o-toluidine), and poly(m-toluidine) prepared from double emulsions stabilized by toluidine isomers as the single surfactant.

Abstract:
HYPOTHESIS
Porous spheres of the conducting polymer polyaniline (PANI) and its derivatives are promising materials for use as functional encapsulants for payload delivery and catalyst supports. Stable water-in-oil-in water (W/O/W) double emulsions can be used to obtain this morphology, but typically require multiple surfactants and stabilizers. A single surfactant system that uses a small amphiphilic molecule is desirable, as it can simplify the method, improve its efficiency, and reduce its cost.

EXPERIMENTS
Granular poly(o-toluidine) (POT) was transformed into porous microspheres when ammonium hydroxide was added to an aqueous acidic dispersion containing the preformed polymer and amphiphilic o-toluidine (OT). The OT, POT, and ammonium hydroxide concentrations were varied to understand the formation mechanism. Conditions were optimized to obtain a narrowed size distribution.

FINDINGS
The rapid change from acidic to alkaline surroundings produces a W/O/W double emulsion from POT and OT over a relatively narrow concentration range. Spheres form when POT dissolves in immiscible OT droplets, and entrapped water droplets form the pores. OT serves as the single amphiphilic surfactant and dissolved POT serves as a hydrophobic co-stabilizer. o-Toluidine, m-toluidine, or p-toluidine could be used as the single surfactant to obtain porous spheres from preformed POT, PANI and poly(m-toluidine).

Hwang|Jean J|JJ|
Soto|Carlos|C|
Lafaurie|Daniel|D|
Stephen|Moses|M|
Sarno|David M|DM|

Porous microspheres
Polyaniline
Poly(o-toluidine)
Poly(m-toluidine)
Toluidine
Single surfactant
W/O/W double emulsions


Improving consistency in large laboratory courses: a design for a standardized practical exam.

Abstract: Laboratory courses serve as important gateways to science, technology, engineering, and mathematics education. One of the challenges in assessing laboratory learning is to conduct meaningful and standardized practical exams, especially for large multisection laboratory courses. Laboratory practical exams in life sciences courses are frequently administered by asking students to move from station to station to answer questions, apply knowledge gained during laboratory experiments, interpret data, and identify various tissues and organs using various microscopic and gross specimens. This approach puts a stringent time limit on all questions regardless of the level of difficulty and also invariably increases the potential risk of cheating. To avoid potential cheating in laboratory courses with multiple sections, the setup for practical exams is often changed in some way between sections. In laboratory courses with multiple instructors or teaching assistants, practical exams may be handled inconsistently among different laboratory sections, due to differences in background knowledge, perceptions of the laboratory goals, or prior teaching experience. In this article, we describe a design for a laboratory practical exam that aims to align the assessment questions with well-defined laboratory learning objectives and improve the consistency among all laboratory sections.

large laboratory course
assessment
laboratory practical exam
backward design
standardized test


Treatment, transport, and primary care involvement when helicopter emergency medical services are inaccessible: a retrospective study.

Abstract:
OBJECTIVE
To examine handling of cancelled helicopter emergency medical services (HEMS) missions with a persisting medical indication.

DESIGN
Retrospective observational study.

SETTING AND SUBJECTS
Cancelled HEMS missions with persisting medical indication within Sogn og Fjordane county in Norway during the period of 2010-2013. Both primary and secondary missions were included.

MAIN OUTCOME MEASURES
Primary care involvement, treatment and cooperation within the prehospital system.

RESULTS
Our analysis included 172 missions with 180 patients. Two-thirds of the patients (118/180) were from primary missions. In 95% (112/118) of primary missions, GPs were alerted, and they examined 62% (70/112) of these patients. Among the patients examined by a GP, 30% (21/70) were accompanied by a GP during transport to hospital. GP involvement did not differ according to time of day (p = 0.601), diagnostic group (p = 0.309), or patient's age (p = 0.409). In 41% of primary missions, the patients received no treatment or oxygen only during transport. Among the secondary missions, 10% (6/62) of patients were intubated or received non-invasive ventilation and were accompanied by a physician or nurse anaesthetist during transport.

CONCLUSIONS
Ambulance workers and GPs have an important role when HEMS is unavailable. Our findings indicated good collaboration among the prehospital personnel. Many of the patients were provided minimal or no treatment, and treatment did not differ according to GP involvement. Key Points Knowledge about handling and involvement of prehospital services in cancelled helicopter emergency medical services (HEMS) missions are scarce. Ambulance workers and general practitioners have an important role when HEMS is unavailable Minimal or no treatment was given to a large amount of the patients, regardless of which health personnel who encountered the patient.

Nystøyl|Dag Ståle|DS|
Hunskaar|Steinar|S|
Breidablik|Hans Johan|HJ|
Østerås|Øyvind|Ø|
Zakariassen|Erik|E|

Emergency medical services
HEMS
Norway
general practitioners
air ambulances
primary health care


Tumor location does not impact oncologic outcomes for percutaneous microwave ablation of clinical T1a renal cell carcinoma.

Abstract:
OBJECTIVE
To evaluate the impact of anterior tumor location on oncologic efficacy, complication rates, and procedure duration for 151 consecutive biopsy-proven clinical T1a renal cell carcinoma (RCC) treated with percutaneous microwave (MW) ablation.

METHODS
This single-center retrospective study was performed under a waiver of informed consent. One hundred forty-eight consecutive patients (103 M/45 F; median age 67 years, IQR 61-73) with 151 cT1a biopsy-proven RCC (median diameter 2.4 cm, IQR 1.9-3.0) were treated with percutaneous MW ablation between March 2011 and August 2017. Patient and procedural data collected included Charlson comorbidity index (CCI), RENAL nephrometry score (NS), use of hydrodisplacement, MW antennas/generator output/time, and procedure time (PT). Data were stratified by anterior, posterior, and midline tumor location and compared with the Kruskal-Wallis or chi-squared tests. The Kaplan-Meier method was used for survival analyses.

RESULTS
Tumor size, NS, and use/volume of hydrodisplacement were similar for posterior and anterior tumors (p > 0.05). Patients with anterior tumors had a higher CCI (3 vs 4, p = 0.001). Median PT for posterior and anterior tumors was similar (100 vs 108 min, p = 0.26). Single session technical success and primary efficacy were achieved for all 151 tumors including 61 posterior and 67 anterior tumors. The 4 (3%) Clavien III-IV complications and 6 (4%) local recurrences were not associated with tumor location (p > 0.05). Three-year RFS, CSS, and OS were 95% (95% CI 0.87, 0.98), 100% (95% CI 1.0, 1.0), and 96% (95% CI 0.89, 0.98), respectively.

CONCLUSIONS
The safety and efficacy of percutaneous microwave ablation for anterior and posterior RCC are similar.

KEY POINTS
• The safety profile for percutaneous microwave ablation of anterior and posterior T1a renal cell carcinoma is equivalent. • Percutaneous microwave ablation of T1a renal cell carcinoma provides durable oncologic control regardless of tumor location. • Placement of additional microwave antennas and use of hydrodisplacement are associated with longer procedure times.

Microwaves
Renal cell carcinoma
Recurrence
Safety


A novel mechanism of vitamin D anti-inflammatory/antioxidative potential in type 2 diabetic patients on metformin therapy.

Abstract:
Introduction
The performed study focused on determining the effect of vitamin D supplementation on enzymes involved in both inflammation and reactive oxygen species (ROS) production and ROS degradation in patients with type 2 diabetes mellitus (T2DM).

Material and methods
The 6-month follow-up, randomized, controlled study included 140 patients with T2DM, ≥ 30 years old, with good metabolic control, treated with metformin and lifestyle advice only. All patients were randomly assigned to two groups (70 each). Patients from the first group (Intervention group) were assigned to receive vitamin D3 50 000 IU or 14 000 IU regarding their vitamin D baseline levels. Patients from the second (Metformin) group continued to receive only metformin during the 6-month study period.

Results
After 6 months, the myeloperoxidase activity was significantly lower and gradually decreased in the Intervention group by about 40%, compared to the baseline measurement (p = 0.015) and compared to the Metformin group (p = 0.001). After 6 months, the xanthine oxidase (XO) activity decreased significantly in the Intervention group compared to the baseline and 3rd month levels (p < 0.001). In the Metformin group there was also a significant decrease in XO after 6 months compared to baseline (p < 0.001) and the 3rd month (p = 0.003). The catalase activity significantly increased within the Intervention group only when comparing the 3rd and 6th month (p = 0.027).

Conclusions
Our study showed that vitamin D may improve endothelial dysfunction in patients with T2DM on metformin therapy by influencing two important factors implicated in the pathogenesis of diabetic complications - ROS production and inflammation, which can additionally contribute to a stable metabolic control during metformin therapy.

Cojic|Milena|M| Kocic|Radivoj|R| Klisic|Aleksandra|A| Cvejanov-Kezunovic|Ljiljana|L| Kavaric|Nebojsa|N| Kocic|Gordana|G|

vitamin D supplementation
myeloperoxidase
xanthine oxidase
diabetes mellitus type 2


Managing highly sensitized renal transplant candidates in the era of kidney paired donation and the new kidney allocation system: Is there still a role for desensitization?

Abstract: Kidney paired donation (KPD) and the new kidney allocation system (KAS) in the United States have led to improved transplantation rates for highly sensitized candidates. We aimed to assess the potential need for other approaches to improve the transplantation rate of highly sensitized candidates such as desensitization. Using the UNOS STAR file, we analyzed transplant rates in a prevalent active waiting-list cohort as of June 1, 2016, followed for 1 year. The overall transplantation rate was 18.9% (11 129/58769). However, only 9.7% (213/2204) of candidates with a calculated panel reactive antibody ≥99.9% received a transplant, and highly sensitized candidates were less likely to receive a living donor transplant. Among candidates with a CPRA ≥ 99.5% (ie. 100%), only 2.5% of transplants were from living donors (13 total, 7 from KPD). Nearly 4 years after KAS (6/30/2018), 1791 actively wait-listed candidates had a CPRA of ≥99.9% and 34.6% (620/1791) of these had ≥5 years of waiting time. Thus, despite KPD and KAS, many sensitized candidates have not been transplanted even with prolonged waiting time. We conclude that candidates with a CPRA ≥ 99.9% and sensitized candidates with an incompatible living donor and prolonged waiting time may benefit from desensitization to improve their ability to receive a transplant.

D000328:Adult
D003888:Desensitization, Immunologic
D046148:Donor Selection
D005260:Female
D005500:Follow-Up Studies
D006680:HLA Antigens
D006650:Histocompatibility Testing
D006801:Humans
D007676:Kidney Failure, Chronic
D016030:Kidney Transplantation
D019520:Living Donors
D008297:Male
D008875:Middle Aged
D040841:Resource Allocation
D012189:Retrospective Studies
D009927:Tissue and Organ Procurement
D066027:Transplant Recipients
D014481:United States

alloantibody
disparities
organ allocation


The Association between Disproportionate Birth Weight to Placental Weight Ratio, Clinical Outcome, and Placental Histopathological Lesions.

Abstract:
INTRODUCTION
High and low birth weight (BW) to placental weight (PW) ratios (BW/PW) have been proposed as markers of placental malfunction. We studied the association of clinical outcome and placental histopathology lesions with BW/PW ratios.

MATERIALS AND METHODS
During the period between 2008 and 2013, placentas from deliveries at gestational age (GA) ≥37 weeks, including both complicated and uncomplicated pregnancies, were sent for histopathology evaluation. Maternal and labor characteristics and pathological reports of the high BW/PW ratio group (>90th), normal BW/PW ratio group (10-90), and low BW/PW ratio group were compared (<10th).

RESULTS
The BW/PW ratio increased as GA increased, with an average GA of 39.4 ± 1.2 weeks in the normal BW/PW ratio group (p < 0.001). Patients with diabetes mellitus and smokers were more common in the low BW/PW ratio group (p < 0.001). Placental maternal stromal vascular lesions and villitis of unknown etiology (VUE) were more common in the high BW/PW ratio group (p < 0.001 and p = 0.03, respectively). By logistic regression analysis, GA, placental maternal stromal vascular lesions, and VUE were found to be independently associated with a high BW/PW ratio, while diabetes mellitus and smoking were independently associated with a low BW/PW ratio.

DISCUSSION
The BW/PW ratio increases significantly beyond 39th weeks, and is associated with an increased rate of placental maternal stromal vascular lesions and VUE.

Ganer Herman|Hadas|H|
Miremberg|Hadas|H|
Schreiber|Letizia|L|
Bar|Jacob|J|
Kovo|Michal|M|

Birth weight
Placental weight
Placenta
Gestational age


Dislocation, Social Isolation, and the Politics of Recovery in Post-Disaster Japan.

Abstract: What happens when temporary shelters become permanent homes? What are the psychosocial impacts of prolonged dislocation, and how might these effects be mitigated through grassroots community activities? Based on fieldwork and interviews with residents in temporary housing and volunteer support groups in northeastern Japan conducted from 2014-2018, this article analyzes the ongoing challenges of delayed recovery, chronic dislocation, and social isolation among survivors of the March 11, 2011 disaster in Japan, with a particular focus on the residents of temporary facilities in Natori City, Miyagi Prefecture. I examine how the complexity of the disaster-recovery process within the local politics of the region has produced new tensions, creating a particular "zoned liminality" for displaced residents while undermining the social nexus of community relations. Then I reflect on certain challenges in treating the psychosocial trauma among survivors, and how their particular needs are addressed through new citizen-based volunteer movements offering holistic activities. These grassroots activities do not necessarily solve the breakdown of social bonds nor improve residents' prospects of returning home. However, by alleviating survivors' sense of social isolation and loneliness, this "humanistic" approach highlights the possibilities of participatory-style psychosocial support that goes beyond conventional biomedical services and top-down, state-driven policies.　.

dislocation
social isolation
Japan
3.11
community mental health
post-disaster mental health
psyschosocial trauma


Use of injectable hormonal contraception and HSV-2 acquisition in a cohort of female sex workers in Vancouver, Canada.

Abstract:
OBJECTIVES
Increased risk of herpes simplex virus 2 (HSV-2) has been proposed as a possible indirect pathway through which hormonal contraceptives (specifically depot medroxyprogesterone acetate (DMPA)) may increase the risk of HIV acquisition among women. We investigated the effects of DMPA on HSV-2 acquisition among female sex workers.

METHODS
Longitudinal data were drawn from a prospective cohort of sex workers in Vancouver, Canada. The primary outcome was HSV-2 seroconversion. Extended Cox regression analyses were used to model the independent effect of DMPA use on HSV-2 acquisition.

RESULTS
Between January 2010 and February 2014, 149 HSV-2 seronegative women were enrolled, contributing to 228 person-years (py) of follow-up. Of these, 19 (13.3%) reported DMPA use. There were 39 HSV-2 seroconversions (12 among DMPA users and 27 among non-users) over the study period (median follow-up of 18.6 months (IQR 8.4-29.9)), resulting in an overall incidence rate of 17.1 cases per 100 py (95% CI 12.4 to 23.6). Incidence rates were higher among DMPA users (57.4 cases per 100 py, 95% CI 31.4 to 105.0) compared with non-users (13.1 cases per 100 py, 95% CI 8.9 to 19.1). After adjusting for key confounders, use of DMPA remained an independent predictor of HSV-2 acquisition (adjusted HR 4.43, 95% CI 1.90 to 10.35).

CONCLUSIONS
The high observed incidence rates of HSV-2, together with a strong association between DMPA exposure and HSV-2 acquisition, raise serious concerns about the provision of optimal reproductive and sexual healthcare to sex workers in this setting. Given the known links between HSV-2 and HIV, our findings underscore the need for further research to better understand the potential association between DMPA and increased risk of HSV-2 and other STIs to help inform the development of safer reproductive choices for women worldwide.

Socías|M Eugenia|ME|
Duff|Putu|P|
Shoveller|Jean|J|
Montaner|Julio S G|JSG|
Nguyen|Paul|P|
Ogilvie|Gina|G|
Shannon|Kate|K|


Effectiveness and safety of unilateral pedicle screw fixation in transforaminal lumbar interbody fusion (TLIF): a systematic review and meta-analysis.

Abstract:
PURPOSE
To evaluate the effectiveness and safety of unilateral pedicle screw fixation in transforaminal lumbar interbody fusion (TLIF) by comparing with bilateral pedicle screw fixation.

MATERIALS AND METHODS
PubMed, EMBASE, and the Cochrane Central Register of Controlled Trial database were used to search and identify clinical prospective trials that evaluated the efficacy and safety of unilateral fixation as compared with bilateral fixation in TLIF surgery. The methodological qualities of studies were assessed using the PEDro (Physiotherapy Evidence Database) score and Newcastle-Ottawa Scale.

RESULTS
Fourteen prospective studies comprising 954 participants were analyzed. Data synthesis show lower fusion rate (P = 0.03) and more cage migration (P = 0.04) in unilateral group compared to bilateral group. There was no significant difference in visual analog scale (VAS), Oswestry Disability Index (ODI), the Short Form 36 Health Survey (SF-36) physical component score (PCS), and length of hospital stay between unilateral and bilateral groups. The unilateral group had shorter operative time (P < 0.00001) and less blood loss (P = 0.0007).

CONCLUSIONS
Based on this systematic review and meta-analysis, the unilateral fixation in TLIF may achieve a similar clinical outcome and reduce blood loss and operative time when compared with that in bilateral fixation. However, the unilateral fixation may produce lower fusion rate and more cage migration than bilateral fixation in TLIF.

Ren|Chunpeng|C| Qin|Rujie|R| Sun|Penghao|P| Wang|Peng|P|

Unilateral
Pedicle screw
Transforaminal lumbar interbody fusion
Meta-analysis
Bilateral


Plasma Ketone and Medium Chain Fatty Acid Response in Humans Consuming Different Medium Chain Triglycerides During a Metabolic Study Day.

Abstract: Background: Medium chain triglycerides (MCT) are ketogenic but the relationship between the change in plasma ketones and the change plasma medium chain fatty acids (MCFA)-octanoate, decanoate, or dodecanoate-after an oral dose of MCT is not well-known. An 8 h metabolic study day is a suitable model to assess the acute effects on plasma ketones and MCFA after a dose of tricaprylin (C8), tricaprin (C10), trilaurin (C12) or mixed MCT (C8C10). Objective: To assess in healthy humans the relationship between the change in plasma ketones, and octanoate, decanoate and dodecanoate in plasma total lipids during an 8 h metabolic study day in which a first 20 ml dose of the homogenized test oil is taken with breakfast and a second 20 ml dose is taken 4 h later without an accompanying meal. Results: The change in plasma acetoacetate, β-hydroxybutyrate and total ketones was highest after C8 (0.5 to 3 h post-dose) and was lower during tests in which octanoate was absent or was diluted by C10 in the test oil. The plasma ketone response was also about 2 fold higher without an accompanying meal (P = 0.012). However, except during the pure C10 test, the response of octanoate, decanoate or dodecanoate in plasma total lipids to the test oils was not affected by consuming an accompanying meal. Except with C12, the 4 h area-under-the-curve of plasma β-hydroxybutyrate/acetoacetate was 2-3 fold higher when no meal was consumed (P < 0.04). Conclusion: C8 was about three times more ketogenic than C10 and about six times more ketogenic than C12 under these acute metabolic test conditions, an effect related to the post-dose increase in octanoate in plasma total lipids.

St-Pierre|Valérie|V|
Vandenberghe|Camille|C|
Lowry|Carolyne-Mary|CM|
Fortier|Mélanie|M|
Castellano|Christian-Alexandre|CA|
Wagner|Richard|R|
Cunnane|Stephen C|SC|

ketones human MCT MCFA acetoacetate β-hydroxybutyrate


Development of TACE Refractoriness Scores in Hepatocellular Carcinoma.

Abstract: Purpose: To identify the independent risk factors for transarterial embolization (TACE) refractoriness and to develop a novel TACE refractoriness score and nomogram for predicting TACE refractoriness in patients with hepatocellular carcinoma (HCC). Methods: Between March 2006 and March 2016, HCC patients who underwent TACE monotherapy as initial treatment at two hospitals formed the study cohort and validation cohort. The criteria of TACE refractoriness followed the Japan Society of Hepatology 2014 version of TACE refractoriness. In the study cohort, the independent risk factors for TACE refractoriness were identified, and TACE refractoriness score and nomogram were then developed. The accuracy of the systems was validated externally in the validation cohort. Results: In total, 113 patients from hospital A formed the study cohort and 122 patients from hospital B formed the validation cohort. In the study cohort, 82.3% of the patients (n = 93) developed TACE refractoriness with a median overall survival (OS) of 540 days (95% CI, 400.8-679.1), and the remaining 20 patients in the TACE-non-refractory group had a median OS of 1,257 days (95% CI, 338.8-2,175.2) (p = 0.019). The median time for developing TACE refractoriness was 207 days (95% CI, 134.8-279.2), and a median number of two TACE procedures were performed after refractoriness developed. The independent risk factors for TACE refractoriness were the number of tumors and bilobular invasion of HCC. TACE refractoriness scores <3.5 indicated a lower incidence of TACE refractoriness, whereas scores >3.5 points indicated a higher incidence (p < 0.001). In the validation cohort, 77.9% of the patients (n = 95) developed TACE refractoriness with a median OS of 568 days (95% CI, 416.3-719.7), and a median OS of 1,324 days was observed in the TACE-non-refractory group (n = 27; 95% CI, 183.5-2,464.5). Conclusions: TACE refractoriness impairs the OS of HCC patients. The number of tumors and bilobular invasion status were independent risk factors for TACE refractoriness. The TACE refractoriness score can be an effective tool and easy approach to predict the risk of TACE refractoriness status.

Chen|Li|L| Yu|Chen-Xi|CX| Zhong|Bin-Yan|BY| Zhu|Hai-Dong|HD| Jin|Zhi-Cheng|ZC| Zhu|Guang-Yu|GY| Zhang|Qi|Q| Ni|Cai-Fang|CF| Teng|Gao-Jun|GJ|

hepatocellular carcinoma
risk factors
nomogram
overall survival
transarterial embolization refractory


Spinal Neurofibroma Masquerading as a Herniated Disc: A case report.

Abstract: We present the only case in English medical literature of a spinal neurofibroma misdiagnosed as a herniated disc using magnetic resonance imaging (MRI). This case presented with typical symptoms and radiological findings of a herniated disc. Intraoperatively, an abnormality was noted at the S1 nerve root sleeve. Further exploration revealed a spinal neurofibroma which was completely resected, resulting in an improvement in the patient's symptoms. Currently, there is heavy reliance on MRI as a highly sensitive and specific tool used in the diagnosis of herniated lumbar discs. Although there have been occasional reports of misdiagnoses using MRI, there are no reported cases of a spinal neurofibroma being misdiagnosed as a herniated lumbar disc. Despite great advances in radiological diagnostic imaging, surgical surprises do still occur. Ultimately, instinct is still essential in intraoperative surgical decisions.

Neurofibroma
Herniated disc
Case report
MRI scan
Misdiagnosis
USA


The Predictive Value of Visceral Adiposity Index and Lipid Accumulation Index for Microalbuminuria in Newly Diagnosed Type 2 Diabetes Patients.

Abstract:
Purpose
This study aims to investigate the predictive value of visceral adiposity index (VAI) and lipid accumulation index (LAP) for microalbuminuria (MAU) in patients with newly diagnosed Type 2 diabetes (T2DM).

Patients and Methods
This study included 335 patients with newly diagnosed T2DM patients from Hebei General Hospital. All the patients aged from 18 to 65 years old include 226 males and 109 females. Patients information and blood indicators were Collected and calculated the LAP and VAI scores. All the patients were divided into males (group A) and females (group B), and these groups were then further subdivided into A1 group which arises microalbuminuria, and A2 group which does not. With the same method, women were divided into B1 group and B2 group.

Results
Baseline data analysis showed that LAP and VAI levels in A1 and B1 groups were significantly higher than those in A2 and B2 groups (P<0.05). Logistic regression analysis showed that fasting blood glucose, waist circumference, LAP, and VAI were independent risk factors for the occurrence of microalbuminuria in both males and females. ROC showed that the area under curve (AUC) of waist circumference, fasting blood glucose, LAP and VAI in male patients were 0.626, 0.676, 0.760 and 0.742, respectively, and in female patients were 0.703, 0.685, 0.787 and 0.764, respectively. In addition, the area under the curve of both LAP and VAI was higher in females than in males.

Conclusion
This study confirmed that both LAP and VAI had predictive values for the occurrence of urinary microalbumin in newly diagnosed T2DM patients. The predictive value was higher in the female group and the suggestion was more applicable to female patients.

Qi|Licui|L| Kang|Ning|N| Li|Yong|Y| Zhao|Hang|H|0000-0002-9531-7574 Chen|Shuchun|S|

visceral adiposity index
lipid accumulation index
microalbuminuria
type 2 diabetes


Live-attenuated RNA hybrid vaccine technology provides single-dose protection against Chikungunya virus.

Abstract: We present a live-attenuated RNA hybrid vaccine technology that uses an RNA vaccine delivery vehicle to deliver in vitro-transcribed, full-length, live-attenuated viral genomes to the site of vaccination. This technology allows ready manufacturing in a cell-free environment, regardless of viral attenuation level, and it promises to avoid many safety and manufacturing challenges of traditional live-attenuated vaccines. We demonstrate this technology through development and testing of a live-attenuated RNA hybrid vaccine against Chikungunya virus (CHIKV), comprised of an in vitro-transcribed, highly attenuated CHIKV genome delivered by a highly stable nanostructured lipid carrier (NLC) formulation as an intramuscular injection. We demonstrate that single-dose immunization of immunocompetent C57BL/6 mice results in induction of high CHIKV-neutralizing antibody titers and protection against mortality and footpad swelling after lethal CHIKV challenge.

Voigt|Emily A|EA|
Fuerte-Stone|Jasmine|J|
Granger|Brian|B|
Archer|Jacob|J|
Van Hoeven|Neal|N|

live-attenuated
hybrid vaccine
Chikungunya
virus
RNA vaccine
nanostructured lipid carrier
arthritis
infection
viral vaccine


Structure of Brewer's Spent Grain Lignin and Its Interactions with Gut Microbiota in Vitro.

Abstract: Lignin is part of dietary fiber, but its conversion in the gastrointestinal tract is not well understood. The aim of this work was to obtain structural information on brewer's spent grain (BSG) lignin and to understand the behavior of the polymeric part of lignin exposed to fecal microbiota. The original BSG and different lignin fractions were characterized by pyrolysis-GC/MS with and without methylation. Methylation pyrolysis proved that the ratio between guaiacyl and syringyl units was similar in all lignin samples, but the ratio between p-coumaric and ferulic acids varied by the isolation method. Combined pyrolysis results indicated higher acylation of γ-OH groups in syringyl than in guaiacyl lignin units. The polymeric lignin structure in the alkali-soluble fraction after enzymatic hydrolysis was slightly altered in the in vitro colon fermentation, whereas lignin in the insoluble residue after enzymatic treatments remained intact.

Ohra-aho|Taina|T| Niemi|Piritta|P| Aura|Anna-Marja|AM| Orlandi|Marco|M| Poutanen|Kaisa|K| Buchert|Johanna|J| Tamminen|Tarja|T|

lignin
Py-GC/MS
TMAH/Py
brewer’s spent grain
colon microbiota
in vitro fermentation


Large nested variant of urothelial carcinoma: a clinicopathological study of 36 cases.

Abstract:
AIMS
The large nested variant of urothelial carcinoma (LNUC) has been added to the World Health Organization (WHO) 2016 classification. Scant data exist, and little is known about its clinical behaviour.

MATERIAL AND RESULTS
Cases fulfilling the morphological criteria of LNUC were collected. Pure and mixed cases (i.e. with other patterns of invasive UC) were studied. Immunohistochemical staining with cytokeratin (CK)7, p63, GATA-3, CK20, p53 and Ki-67 was performed. Included were 26 cystectomies (RC) and 10 resections (TURB) belonging to 36 patients with an average age of 66.7 years. Fourteen (39%) were pure LNUCs, and 22 (61%) displayed mixed features. Seventy per cent of the TURBs had pT2 tumours, while 58% of RCs had extravesical disease (≥pT3 and/or ≥pN1), with the rate of advanced disease being higher in mixed (69%) in comparison to pure cases (40%). Similarly, 38% of mixed cases had nodal metastases in comparison to 20% of pure cases. Overall, eight patients (24%) died of disease at a mean interval time of 21.7 months and seven patients (21%) showed recurrence or metastases. Disease progression was significantly higher in mixed cases (55 and 31% in mixed and pure cases, respectively). Positive staining was: CK7 = 87.5%, CK20 = 72%, GATA-3 = 91%, P63 = 100%, p53 = 56% and Ki-67 = mean of 16%.

CONCLUSION
Despite the bland cytological appearance and deceptive pattern of invasion of the LNUC, our study validates its fully malignant potential with metastatic spread and tumour-related deaths. Distinguishing mixed from pure LNUCs seems to be of value. LNUCs show comparable immunophenotype to both conventional urothelial carcinoma and the nested variant of urothelial carcinoma.

large nested
urothelial carcinoma
pure
bladder cancer
prognosis


Regenerative Endodontic Procedures for the Treatment of Necrotic Mature Teeth with Apical Periodontitis: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Abstract:
INTRODUCTION
Regenerative endodontic procedures (REPs) are intended to repair and regenerate part of the pulp-dentin complex. The aim of this study was to systematically appraise the existing evidence on the effectiveness of REPs on mature teeth with pulp necrosis and apical periodontitis.

METHODS
Electronic database and hand searches were performed on 8 databases of published and unpublished literature from inception to January 3, 2021, for the identification of randomized controlled trials (RCTs) or prospective clinical trials. The related key words included "regenerative," "pulp revascularization," "revitalization procedure," and "necrotic mature teeth." A random effects meta-analysis was conducted assessing success as the main outcome treatment. Risk of bias was assessed through the Cochrane Risk of Bias 2.0 tool, and the quality of the evidence was assessed with the Grading of Recommendations Assessment, Development and Evaluation approach.

RESULTS
Of the 337 initial hits, 4 RCTs were eligible for inclusion, whereas 3 were included in the quantitative synthesis. Overall, there was no difference in the relative risk for a successful/unsuccessful treatment outcome between REPs or conventional treatment (3 studies, relative risk = 1.03; 95% confidence interval, 0.92-1.15; P = .61; heterogeneity I2 = 0.0%, P = .53; prediction interval = 0.51-2.09). Risk of bias ranged from low to raising some concerns, whereas the quality of the evidence was graded as moderate.

CONCLUSIONS
Based on moderate-quality evidence, REPs appear as a viable treatment alternative for mature necrotic teeth with periapical lesions at present. Furthermore, well-designed RCTs might also provide confirmatory evidence in this respect while also framing a backbone for standardization of the therapeutic protocol of REPs.

Glynis|Antonios|A|
Foschi|Federico|F|
Kefalou|Ismini|I|
Koletsi|Despina|D|
Tzanetakis|Giorgos N|GN|

D016032:Randomized Controlled Trials as Topic

regenerative endodontic procedures
necrotic mature teeth
Apical periodontitis
meta-analysis
conventional endodontic treatment


Examining the Overlap Between ADHD and Autism Spectrum Disorder (ASD) Using Candidate Endophenotypes of ADHD.

Abstract:
Objective: Recent discussions of aetiological overlap between ADHD and Autism Spectrum Disorder (ASD) require comparative studying of these disorders.

METHOD
We examined performance of ASD patients with (ASD+) and without (ASD-) comorbid ADHD, ADHD patients, and controls for selected putative endophenotypes of ADHD: Intrasubject Variability (ISV) of reaction times, working memory (WM), inhibition, and temporal processing.

RESULTS
We found that patients with ADHD or ASD+, but not ASD-, had elevated ISV across the entire task battery and temporal processing deficits, and that none of the groups were impaired in WM or inhibition. High levels of ISV and generally poor performance in ASD+ patients were only partially due to additive effects of the pure disorders.

CONCLUSION
Overall, we conclude that, within our limited but heterogeneous task battery, ISV and temporal processing deficits are most sensitive to ADHD symptomatology and that controlling for ADHD comorbidity is mandatory when assessing ISV in autism.

Salunkhe|G|G|
Weissbrodt|K|K|
Feige|B|B|
Saville|C W N|CWN|
Berger|A|A|
Dundon|N M|NM|
Bender|S|S|
Smyrnis|N|N|
Beauducel|A|A|
Biscaldi|M|M|
Klein|C|C|

D001289:Attention Deficit Disorder with Hyperactivity

endophenotypes
intrasubject variability
working memory
response inhibition
temporal reproduction


CD8+ lineage dendritic cells determine adaptive immune responses to inflammasome activation upon sterile skin injury.

Abstract: The molecular links between sterile inflammation and induction of adaptive immunity have not been fully identified. Here, we examine how damage-associated molecular patterns (DAMPs), as opposed to pathogen-associated molecules (PAMPs), regulate the immune response to non-self-antigens presented at the site of a physical injury. Heat applied briefly to the skin invokes sterile inflammation, characterized by local cell death and caspase-1 activation without demonstrably disrupting skin integrity. Co-delivery of ovalbumin (OVA) with heat injury induces OVA-specific CD8+ T-cell responses, and this is dependent on caspase-1 activation and MyD88 signalling. Using Id2flox/flox-CD11cCre+ mice, we demonstrate that CD8+ lineage DCs are required to induce OVA-specific CD8+ T-cell responses following heat injury. Consistent with this observation, intradermal administration of CD8+ lineage DCs but not CD11b+ lineage DCs restores priming of CD8+ T-cell responses in Casp-1-/- mice. Thus, we conclude that a sterile injury induces CD8+ T-cell immune responses to local antigen through caspase-1 activation and requires CD8+ lineage DCs, a finding of significance for immunotherapy and for the pathogenesis of autoimmunity.

Chakraborty|Rituparna|R|
Chandra|Janin|J|
Cui|Shuai|S|
Tolley|Lynn|L|
Cooper|Matthew A|MA|
Kendall|Mark|M|
Frazer|Ian H|IH|0000-0002-8002-4680

D053594:Myeloid Differentiation Factor 88

Caspase-1
heat injury
OVA-specific CD8+ T-cell responses
MyD88 signalling
toll-like receptor


Reduced emotional responsiveness in individuals with marginal elevation in blood pressure within the normal range: Evidence from altered affect-modulated startle response.

Abstract: Reduced responsiveness to emotional stimuli ('emotional dampening') has been observed in normotensives with elevated blood pressure (BP) and hypertensives but it is not known whether this is due to aberrant responding to emotional information at the involuntary level and whether it is also associated with minimal elevations in BP in the normal range. In this study, we examined emotional dampening using the affect-modulated startle paradigm given its proven sensitivity to motivational states of approach and withdrawal, typically independent of conscious intentional control. Acoustically elicited startle eye-blink modulation was measured using electromyography of the orbicularis oculi muscle beneath the left eye in 59 healthy individuals while they viewed pleasant, unpleasant and neutral standardized pictures. The expected startle attenuation to pleasant pictures, and startle potentiation to unpleasant pictures, relative to neutral pictures, was found in people in the comparison (N = 29) but not elevated BP (N = 30) group. This finding was further supported by significant moderating effect (assessed using ANCOVA and sub-sample analysis) of BP on valence-startle amplitude relationship. The comparison BP group also showed slower latencies to response onset for pleasant stimuli compared to neutral and unpleasant, with no effect of valence in the elevated BP group. However, BP did not moderate the valence-onset latency relationship. Our findings indicate that previously reported emotional dampening associated with elevated BP extends to reduced involuntary emotional reactivity and to individuals with even minimal BP elevations (i.e. higher but still within the normal range). Future research needs to confirm these findings in hypertensive individuals, preferably using within-subjects designs.

Shukla|Meenakshi|M|
Lau|Jennifer Y F|JYF|
Lissek|Shmuel|S|
Pandey|Rakesh|R|
Kumari|Veena|V|

Elevated blood pressure
BP
Hypertension
Emotional responding
Startle amplitude


Heterocyclic Analogs of Sulforaphane Trigger DNA Damage and Impede DNA Repair in Colon Cancer Cells: Interplay of HATs and HDACs.

Abstract:
SCOPE
DNA repair inhibitors have broad clinical applications in tumor types with DNA repair defects, including colorectal cancer (CRC). Structural analogs of the anticancer agent sulforaphane (SFN) were investigated as modifiers of histone deacetylase (HDAC) and histone acetyltransferase (HAT) activity, and for effects on DNA damage/repair pertinent to human CRC.

METHODS AND RESULTS
In the polyposis in rat colon (Pirc) model, single oral administration of SFN and structurally related long-chain isothiocyanates (ITCs) decreased histone deacetylase 3 (HDAC3) expression and increased pH2AX levels markedly in adenomatous colon polyps, extending prior observations on HDAC3 inhibition/turnover in cell-based assays. Colon cancer cells at a high initial plating density had diminished cytotoxicity from SFN, whereas novel tetrazole-containing heterocyclic analogs of SFN retained their efficacy. The potent SFN analogs triggered DNA damage, cell cycle arrest, apoptosis, and loss of a key DNA repair regulator, C-terminal binding protein (CtBP) interacting protein (CtIP). These SFN analogs also altered HAT/HDAC activities and histone acetylation status, lowered the expression of HDAC3, P300/CBP-associated factor (PCAF) and lysine acetyltransferase 2A (KAT2A/GCN5), and attenuated homologous recombination (HR)/non-homologous end joining (NHEJ) repair activities in colon cancer cells.

CONCLUSION
Novel tetrazole-containing heterocyclic analogs of SFN provide a new avenue for chemosensitization in colon cancer cells via modulation of HAT/HDAC activities and associated DNA damage/repair signaling pathways.

Okonkwo|Adaobi|A|
Mitra|Joy|J|
Johnson|Gavin S|GS|
Li|Li|L|
Dashwood|Wan Mohaiza|WM|
Hegde|Muralidhar L|ML|
Yue|Chen|C|
Dashwood|Roderick H|RH|
Rajendran|Praveen|P|


Molecular dynamics of Dkk4 modulates Wnt action and regulates meibomian gland development.

Abstract: Secreted Dickkopf (Dkk) proteins are major Wnt pathway modulators during organ development. Dkk1 has been widely studied and acts as a general Wnt inhibitor. However, the molecular function of other Dkks remains largely unknown. Here, we show that Dkk4 selectively inhibits a subset of Wnts, but is further inactivated by proteolytic cleavage. Meibomian gland (MG) formation is employed as a model where Dkk4 and its Wnt targets are expressed. Skin-specific expression of Dkk4 arrests MG growth at early germ phase, which is similar to that observed in Eda-ablated Tabby mice. Consistent with transient Dkk4 action, intact Dkk4 inhibits MG extension but the cleaved form progressively increases during MG development with a concomitant upswing in Wnt activity. Furthermore, both Dkk4 and its receptor (and Wnt co-receptor) Lrp6 are direct Eda targets during MG induction. In cell and organotypic cultures, Dkk4 inhibition is eliminated by elevation of Lrp6. Also, Lrp6 upregulation restores MG formation in Tabby mice. Thus, the dynamic state of Dkk4 itself and its interaction with Lrp6 modulates Wnt function during MG development, with a novel limitation of Dkk4 action by proteolytic cleavage.

Sima|Jian|J|0000-0002-9082-2061 Piao|Yulan|Y| Chen|Yaohui|Y| Schlessinger|David|D|

D036341:Intercellular Signaling Peptides and Proteins

D060488:Low Density Lipoprotein Receptor-Related Protein-6

Dkk4
Wnt
Meibomian gland
Proteolytic cleavage
Lrp6
Eda
Mouse


Application of Blue Filters Increases the Usefulness of Moreland Test in Anomaloscopic Color Vision Assessment for Blue-Green Color Range.

Abstract: The effect of blue light filters on the anomaloscopic examination was analyzed. Thirty subjects (18-43 y, 20 female, 10 male) without color vision disorders were examined in 4 filter conditions: no filter (F-0), Blue Control Hoya (F-BC), Med-1 JZO (F-Med1) and 450 Eschenbach (F-450). Both Rayleigh test (red-green axis) and Moreland test (blue-green axis) were performed. Application of F-BC filter shows negligible effect on color vision perception in both tests. Contrary to this, the application of strong F-450 filter causes significant shift in Moreland test towards tritanopy and the decrease in correlations of Moreland parameters with Rayleigh test parameters. The application of medium strong F-Med1 filter causes the slight shift in Moreland test towards the center of the Moreland scale and increases the Spearman correlations between Moreland and Rayleigh test parameters. This observation suggests that the about 15-40% reduction of blue diode intensity in the Moreland test may be beneficial in detecting mild changes in color vision perception in the blue-green axis and may improve its usefulness in evaluating the color vision perception disorders accompanying different illnesses, such as diabetes, glaucoma, neuritis optica, or cataract. The discussion concerning the modifications of Moreland test construction is also presented.

Moreland
anomaloscope
color vision
Rayleigh


Clinical, radiographic, and restorative peri-implant measurements of narrow and standard diameter implants in obese and nonobese patients: A 3-year retrospective follow-up study.

Abstract:
BACKGROUND
There is dearth of studies assessing clinical, restorative, and radiographic peri-implant outcomes around narrow diameter implants (NDIs) and standard diameter implants (SDIs) in obese and nonobese subjects.

OBJECTIVE
To assess clinical, restorative, and radiographic parameters of NDIs and SDIs placed in obese and nonobese individuals.

MATERIALS AND METHODS
Obese and nonobese patients requiring NDIs and SDIs in the anterior maxilla/mandible were included. Based on the implant diameter, participants were further divided into two subgroups: (a) NDIs (3.3 mm) and (b) SDIs (4.1 mm). Peri-implant clinical measurements including plaque index (PI), bleeding on probing (BOP), probing depth (PD), and radiographic crestal bone loss (CBL) were evaluated around NDIs and SDIs at 1 and 3-year follow-up.

RESULTS
A total of 70 patients (35 obese and 35 nonobese) were included. Only BOP showed statistically significant differences between both the groups at patient level at 1 and 3-year follow-up (P < .05). There was no statistically significant difference in PI and PD around NDIs and SDIs between obese and nonobase patients. Statistical significant differences were observed in the total CBL around NDIs and RDIs among obese and nonbase subjects at 3 year follow-up (P < .05).

CONCLUSION
Both NDIs and SDIs show consistent clinical stability among obese and nonobase patients. Higher amount of bone loss was observed in obese patients compared to nonobase patients despite regular hygiene maintenance.

D016301:Alveolar Bone Loss
D015921:Dental Implants
D003774:Dental Plaque Index
D005500:Follow-Up Studies
D006801:Humans
D009765:Obesity
D012189:Retrospective Studies

obesity
crestal bone loss
narrow implants
standard-diameter implants


Ubiquitin-specific protease 7 promotes ferroptosis via activation of the p53/TfR1 pathway in the rat hearts after ischemia/reperfusion.

Abstract: Iron overload triggers the ferroptosis in the heart following ischemia/reperfusion (I/R) and transferrin receptor 1 (TfR1) charges the cellular iron uptake. Bioinformatics analysis shows that the three molecules of ubiquitin-specific protease 7 (USP7), p53 and TfR1 form a unique pathway of USP7/p53/TfR1. This study aims to explore whether USP7/p53/TfR1 pathway promotes ferroptosis in rat hearts suffered I/R and the underlying mechanisms. The SD rat hearts were subjected to 1 h-ischemia plus 3 h-reperfusion, showing myocardial injury (increase in creatine kinase release, infarct size, myocardial fiber loss and disarray) and up-regulation of USP7, p53 and TfR1 concomitant with an increase of ferroptosis (reflecting by accumulation of iron and lipid peroxidation while decrease of glutathione peroxidase activity). Inhibition of USP7 activated p53 via suppressing deubiquitination, which led to down-regulation of TfR1, accompanied by the decreased ferroptosis and myocardial I/R injury. Next, H9c2 cells underwent hypoxia/reoxygenation (H/R) in vitro to mimic the myocardial I/R model in vivo. Consistent with the results in vivo, inhibition or knockdown of USP7 reduced the H/R injury (decrease of LDH release and necrosis) and enhanced the ubiquitination of p53 along with the decreased levels of p53 and TfR1 as well as the attenuated ferroptosis (manifesting as the decreased iron content and lipid peroxidation while the increased GPX activity). Knockdown of TfR1 inhibited H/R-induced ferroptosis without p53 deubiquitination. Based on these observations, we conclude that a novel pathway of USP7/p53/TfR1 has been identified in the I/R-treated rat hearts, where up-regulation of USP7promotes ferrptosis via activation of the p53/TfR1 pathway.

Tang|Li-Jing|LJ| Zhou|Yuan-Jing|YJ| Xiong|Xiao-Ming|XM| Li|Nian-Sheng|NS| Zhang|Jie-Jie|JJ| Luo|Xiu-Ju|XJ| Peng|Jun|J|

Ubiquitin-specific protease 7
Ferroptosis
p53
Ischemia/reperfusion
Transferrin receptor 1


CT spectral imaging for monitoring the therapeutic efficacy of VEGF receptor kinase inhibitor AG-013736 in rabbit VX2 liver tumours.

Abstract:
PURPOSE
The aim of this study was to evaluate the value of computed tomography (CT) spectral imaging in assessing the therapeutic efficacy of a vascular endothelial growth factor (VEGF) receptor inhibitor AG-013736 in rabbit VX2 liver tumours.

METHODS
Twenty-three VX2 liver tumour-bearing rabbits were scanned with CT in spectral imaging mode during the arterial phase (AP) and portal phase (PP). The iodine concentrations(ICs)of tumours normalized to aorta (nICs) at different time points (baseline, 2, 4, 7, 10, and 14 days after treatment) were compared within the treated group (n = 17) as well as between the control (n = 6) and treated groups. Correlations between the tumour size, necrotic fraction (NF), microvessel density (MVD), and nICs were analysed.

RESULTS
The change of nICs relative to baseline in the treated group was lower compared to the control group. A greater decrease in the nIC of a tumour at 2 days was positively correlated with a smaller increase in tumour size at 14 days (P < 0.05 for both). The tumour nIC values in AP and PP had correlations with MVD (r = 0.71 and 0.52) and NF (r = -0.54 and -0.51) (P < 0.05 for all).

CONCLUSIONS
CT spectral imaging allows for the evaluation and early prediction of tumour response to AG-013736.

KEY POINTS
• AG-013736 treatment response was evaluated by CT in a rabbit tumour model. • CT spectral imaging allows for the early treatment monitoring of targeted anti-tumour therapies. • Spectral CT findings correlated with vascular changes after anti-tumour therapies. • Spectral CT is a promising method for assessing clinical treatment response.

Lv|Peijie|P| Liu|Jie|J| Yan|Xiaopeng|X| Chai|Yaru|Y| Chen|Yan|Y| Gao|Jianbo|J| Pan|Yuanwei|Y| Li|Shuai|S| Guo|Hua|H| Zhou|Yue|Y|

D040262:Receptors, Vascular Endothelial Growth Factor

CT spectral imaging
Liver tumour
Computed tomography
Animal experience
Vascular targeting agent


A diarylpentanoid curcumin analog exhibits improved radioprotective potential in the intestinal mucosa.

Abstract:
PURPOSE
To best enhance the effects of radiotherapy, it is important to minimize adverse events, including free radical-induced intestinal cell damage. Given the threat of nuclear power plant accidents or nuclear terrorism, there is an urgent need for radioprotectants to counteract the radiation-induced toxicity and/or injuries. Curcumin exhibits protective effects against gamma irradiation; however, its in vivo efficacy is decreased due to the low bioavailability. We examined the radioprotective effect of a newly synthesized curcumin analog, GO-Y031, on 11-Gy X-ray-induced intestinal mucosal damage in mice.

MATERIALS AND METHODS
The radioprotection experiments were conducted by using C57BL/6J or Jcl:ICR mice. Molecules related to radiation damage, including p53, Bax, Bcl-2, cleaved caspase-3, and reactive carbonyl species (RCS), were investigated immunohistochemically.

RESULTS
GO-Y031 protected against crypt hypoplasia relative to a mock treatment at 0.5% (weight/weight); the number of crypts were 11.00 ± 2.00/circumference (mm) in treated versus 6.86 ± 0.99/mm in mock-treated C57BL/6 mice (p = 0.0079). GO-Y031 also reduced the levels of RCS, p53, and cleaved caspase-3 accumulation in the irradiated intestinal cells.

CONCLUSIONS
GO-Y031 suppresses the accumulation of RCS and apoptosis-related molecules in irradiated cells. This compound may be a good primary radioprotective compound.

Fukuda|Koji|K| Uehara|Yoshihiko|Y| Nakata|Eiko|E| Inoue|Masahiro|M| Shimazu|Kazuhiro|K| Yoshida|Taichi|T| Kanda|Hiroaki|H| Nanjo|Hiroshi|H| Hosoi|Yoshio|Y| Yamakoshi|Hiroyuki|H| Iwabuchi|Yoshiharu|Y| Shibata|Hiroyuki|H|

Curcumin
radioprotection
intestinal damage


Protocol for a prospective, school-based standardisation study of a digital social skills assessment tool for children: The Paediatric Evaluation of Emotions, Relationships, and Socialisation (PEERS) study.

Abstract:
BACKGROUND
Humans are by nature a social species, with much of human experience spent in social interaction. Unsurprisingly, social functioning is crucial to well-being and quality of life across the lifespan. While early intervention for social problems appears promising, our ability to identify the specific impairments underlying their social problems (eg, social communication) is restricted by a dearth of accurate, ecologically valid and comprehensive child-direct assessment tools. Current tools are largely limited to parent and teacher ratings scales, which may identify social dysfunction, but not its underlying cause, or adult-based experimental tools, which lack age-appropriate norms. The present study describes the development and standardisation of Paediatric Evaluation of Emotions, Relationships, and Socialisation (PEERS®), an iPad-based social skills assessment tool.

METHODS
The PEERS project is a cross-sectional study involving two groups: (1) a normative group, recruited from early childhood, primary and secondary schools across metropolitan and regional Victoria, Australia; and (2) a clinical group, ascertained from outpatient services at The Royal Children's Hospital Melbourne (RCH). The project aims to establish normative data for PEERS®, a novel and comprehensive app-delivered child-direct measure of social skills for children and youth. The project involves recruiting and assessing 1000 children aged 4.0-17.11 years. Assessments consist of an intellectual screen, PEERS® subtests, and PEERS-Q, a self-report questionnaire of social skills. Parents and teachers also complete questionnaires relating to participants' social skills. Main analyses will comprise regression-based continuous norming, factor analysis and psychometric analysis of PEERS® and PEERS-Q.

ETHICS AND DISSEMINATION
Ethics approval has been obtained through the RCH Human Research Ethics Committee (34046), the Victorian Government Department of Education and Early Childhood Development (002318), and Catholic Education Melbourne (2166). Findings will be disseminated through international conferences and peer-reviewed journals. Following standardisation of PEERS®, the tool will be made commercially available.

Thompson|Emma J|EJ|
Beauchamp|Miriam H|MH|
Darling|Simone J|SJ|
Hearps|Stephen J C|SJC|
Brown|Amy|A|
Charalambous|George|G|
Crossley|Louise|L|
Darby|David|D|
Dooley|Julian J|JJ|
Greenham|Mardee|M|
Jaimangal|Mohinder|M|
McDonald|Skye|S|
Muscara|Frank|F|
Turkstra|Lyn|L|
Anderson|Vicki A|VA|

development
adolescent
child
social cognition
test measurement


Accuracy and Time Delay of Glucose Measurements of Continuous Glucose Monitoring and Bedside Artificial Pancreas During Hyperglycemic and Euglycemic Hyperinsulinemic Glucose Clamp Study.

Abstract:
BACKGROUND
Glucose values of continuous glucose monitoring (CGM) have time delays compared with plasma glucose (PG) values. The artificial pancreas (STG-55, Nikkiso, Japan) (AP), which measures venous blood glucose directly, also has a time delay because of the long tubing lines from sampling vessel to the glucose sensor. We investigate accuracy and time delay of CGM and AP in comparison with PG values during 2-step glucose clamp study.

METHODS
Seven patients with type 2 diabetes and 2 healthy volunteers were included in this study. CGM (Enlite sensor, Medtronic, Northridge, CA, USA) was attached on the day before the experiment. Hyperglycemic (200 mg/dL) clamp was performed for 90 minutes, followed by euglycemic (100 mg/dL) hyperinsulinemic (100 μU/mL) clamp for 90-120 minutes using AP. CGM sensor glucose was calibrated just before and after the clamp study. AP and CGM values were compared with PG values.

RESULTS
AP values were significantly lower than PG values at 5, 30 minute during hyperglycemic clamp. In comparison, CGM value at 0 minute was significantly higher, and its following values were almost significantly lower than PG values. The time delay of AP and CGM values to reach maximum glucose levels were 5.0 ± 22.3 (NS) and 28.6 ± 32.5 ( P < .05) min, respectively. Mean absolute rate difference of CGM was significantly higher than AP (24.0 ± 7.6 vs 15.3 ± 4.6, P < .05) during glucose rising period (0-45 min); however, there were no significant differences during other periods.

CONCLUSIONS
Both CGM and AP failed to follow plasma glucose values during nonphysiologically rapid glucose rising, but indicated accurate values during physiological glucose change.

Kuroda|Akio|A| Taniguchi|Satoshi|S| Akehi|Yuko|Y| Mori|Hiroyasu|H| Tamaki|Motoyuki|M| Suzuki|Reiko|R| Otsuka|Yinhua|Y| Matsuhisa|Munehide|M|

D000328:Adult
D015415:Biomarkers
D001786:Blood Glucose
D003924:Diabetes Mellitus, Type 2
D005260:Female
D015309:Glucose Clamp Technique
D006801:Humans
D007004:Hypoglycemic Agents
D007328:Insulin
D007332:Insulin Infusion Systems
D008297:Male
D008875:Middle Aged
D018670:Monitoring, Ambulatory
D019397:Pancreas, Artificial
D019095:Point-of-Care Systems
D011237:Predictive Value of Tests
D015203:Reproducibility of Results
D012189:Retrospective Studies
D013997:Time Factors
D016896:Treatment Outcome

continuous glucose monitoring
artificial pancreas
Parkes consensus error grid
euglycemic hyperinsulinemic clamp study
hyperglycemic clamp study


Probing the interaction interface of the GADD45β/MKK7 and MKK7/DTP3 complexes by chemical cross-linking mass spectrometry.

Abstract: GADD45β is selectively and constitutively expressed in Multiple Myeloma cells, and this expression correlates with an unfavourable clinical outcome. GADD45β physically interacts with the JNK kinase, MKK7, inhibiting its activity to enable the survival of cancer cells. DTP3 is a small peptide inhibitor of the GADD45β/MKK7 complex and is able to restore MKK7/JNK activation, thereby promoting selective cell death of GADD45β-overexpressing cancer cells. Enzymatic MS foot-printing and diazirine-based chemical cross-linking MS (CX-MS) strategies were applied to study the interactions between GADD45β and MKK7 kinase domain (MKK7_KD) and between DTP3 and MKK7_KD. Our data show that the binding between GADD45β and MKK7 largely occurs between GADD45β loop 2 (region 103-117) and the kinase enzymatic pocket. We also show that DTP3 interferes with this GADD45β/MKK7 interaction by contacting the MKK7 peptides, 113-136 and 259-274. Accordingly, an MKK7_KD Δ(101-136) variant lacking Trp135 did not produce a fluorescence quenching effect upon the binding of DTP3. The assessment of the interaction between GADD45β and MKK7 and the elucidation of the recognition surfaces between DTP3 and MKK7 significantly advance the understanding of the mechanism underlying the inhibition of the GADD45β/MKK7 interaction by DTP3 and pave the way to the design of small-molecule DTP3 analogues.

Rega|Camilla|C|
Russo|Rosita|R|
Focà|Annalia|A|
Sandomenico|Annamaria|A|
Iaccarino|Emanuela|E|
Raimondo|Domenico|D|
Milanetti|Edoardo|E|
Tornatore|Laura|L|
Franzoso|Guido|G|
Pedone|Paolo Vincenzo|PV|
Ruvo|Menotti|M|
Chambery|Angela|A|

D000943:Antigens, Differentiation
D006801:Humans
D048688:MAP Kinase Kinase 7
D013058:Mass Spectrometry
D046912:Multiprotein Complexes
D010455:Peptides
D047428:Protein Kinase Inhibitors


Religion, social interactions, and COVID-19 incidence in Western Germany.

Abstract: This paper investigates how social interactions, as shaped by religious denomination, are related to COVID-19 incidence and associated mortality in Western Germany. We observe that the number of infections and deaths during the early pandemic phase were much higher in predominantly Catholic counties with arguably stronger family and social ties. The relationship was confirmed at the county level through numerous robustness checks, and after controlling for a series of characteristics and county fixed effects. At the individual level, we confirmed that Catholics, relative to non-Catholics, have tighter and more frequent interactions with their family and friends. Moreover, the intensity of social interaction was able to partially explain the relationship between COVID-19 incidence and share of Catholics at the county level. Our results highlight the number of dimensions that have to be taken into account when designing and implementing mitigation measures in the early stages of disease outbreaks.


Extensive spinal extradural ganglioneuroma of the lumbar spine: mimicking lymphoma.

Abstract:
BACKGROUND
Ganglioneuromas are rare, benign, well-differentiated tumors arising from neural crest cells that commonly occur in the posterior mediastinum, retroperitoneum, cervical spine, and adrenal gland. We report an unusual case of an extensive spinal extradural ganglioneuroma, circumferentially and longitudinally affecting the extradural space of the lumbar spine and continuously invading bilateral psoas muscles.

CASE DESCRIPTION
A 32-year-old man presented with a 1-week history of abdominal pain and diarrhea. Radiographs revealed scalloping of the posterior surfaces of the L2 and L3 vertebral bodies and widening of L2-3 and L3-4 bilateral intervertebral foramina. Computed tomography scans and magnetic resonance imaging showed a well-defined lobulated extradural mass from L1 to L4 and a continuously forming mass in the psoas muscles through L2-3 bilateral neural foramina. The mass demonstrated homogeneously isointense signal on T1-weighted images, inhomogeneously hyperintense-to-isointense signal on T2-weighted images, and inhomogeneous enhancement on fat-suppressed contrast-enhanced T1-weighted images. Radiologic diagnosis included spinal epidural lymphoma. Percutaneous biopsy with sonographic guidance was performed, and the mass was diagnosed on pathological examination as a ganglioneuroma.

CONCLUSIONS
This is the first known reported case in the literature of a spinal extradural ganglioneuroma with circumferentially and longitudinally extensive involvement of the extradural space and a large psoas mass.

Extradural
Ganglioneuroma
Lumbar spine
Lymphoma
Spinal tumor


Prevalence of adjacent segment disc degeneration in patients undergoing anterior cervical discectomy and fusion based on pre-operative MRI findings.

Abstract: Anterior cervical discectomy and fusion (ACDF) is a widely accepted surgical treatment for symptomatic cervical spondylosis. Some patients develop symptomatic adjacent segment degeneration, occasionally requiring further treatment. The cause and prevalence of adjacent segment degeneration and disease is unclear at present. Proponents for motion preserving surgery such as disc arthroplasty argue that this technique may decrease the "strain" on adjacent discs and thus decrease the incidence of symptomatic adjacent segment degeneration. The purpose of this study was to assess the pre-operative prevalence of adjacent segment degeneration in patients undergoing ACDF. A database review of three surgeons' practice was carried out to identify patients who had undergone a one- or two-level ACDF for degenerative disc disease. Patients were excluded if they were operated on for recent trauma, had an inflammatory arthropathy (for example, rheumatoid arthritis), or had previous spine surgery. The pre-operative MRI of each patient was reviewed and graded using a standardised methodology. One hundred and six patient MRI studies were reviewed. All patients showed some evidence of intervertebral disc degeneration adjacent to the planned operative segment(s). Increased severity of disc degeneration was associated with increased age and operative level, but was not associated with sagittal alignment. Disc degeneration was more common at levels adjacent to the surgical level than at non-adjacent segments, and was more severe at the superior adjacent level compared with the inferior adjacent level. These findings support the theory that adjacent segment degeneration following ACDF is due in part to the natural history of cervical spondylosis.

Lundine|Kristopher M|KM|
Davis|Gavin|G|
Rogers|Myron|M|
Staples|Margaret|M|
Quan|Gerald|G|

Disc degeneration
Adjacent segment disease
Anterior cervical fusion
Cervical disc disease
Magnetic resonance imaging


Metabolic differentiation and classification of abnormal Savda Munziq's pharmacodynamic role on rat models with different diseases by nuclear magnetic resonance-based metabonomics.

Abstract:
BACKGROUND
Abnormal Savda Munziq (ASMq) is a traditional Uyghur herbal preparation used as a therapy for abnormal Savda-related diseases. In this study, we investigate ASMq's dynamic effects on abnormal Savda rat models under different disease conditions.

MATERIALS AND METHODS
Abnormal Savda rat models with hepatocellular carcinoma (HCC), type 2 diabetes mellitus (T2DM), and asthma dosed of ASMq. Serum samples of each animal tested by nuclear magnetic resonance spectroscopy and analyzed by orthogonal projection to latent structure with discriminant analysis.

RESULTS
Compared with healthy controls, HCC rats had higher concentrations of amino acids, fat-related metabolites, lactate, myoinositol, and citrate, but lower concentrations of α-glucose, β-glucose, and glutamine. Following ASMq treatment, the serum acetone very low-density lipoprotein (VLDL), LDL, unsaturated lipids, acetylcysteine, and pyruvate concentration decreased, but α-glucose, β-glucose, and glutamine concentration increased (P < 0.05). T2DM rats had higher concentrations of α- and β-glucose, but lower concentrations of isoleucine, leucine, valine, glutamine, glycoprotein, lactate, tyrosine, creatine, alanine, carnitine, and phenylalanine. After ASMq treated T2DM groups showed reduced α- and β-glucose and increased creatine levels (P < 0.05). Asthma rats had higher acetate, carnitine, formate, and phenylalanine levels, but lower concentrations of glutamine, glycoprotein, lactate, VLDL, LDL, and unsaturated lipids. ASMq treatment showed increased glutamine and reduced carnitine, glycoprotein, formate, and phenylalanine levels (P < 0.05).

CONCLUSION
Low immune function, decreased oxidative defense, liver function abnormalities, amino acid deficiencies, and energy metabolism disorders are common characteristics of abnormal Savda-related diseases. ASMq may improve the abnormal metabolism and immune function of rat models with different diseases combined abnormal Savda.

Mamtimin|Batur|B| Xia|Guo|G| Mijit|Mahmut|M| Hizbulla|Mawlanjan|M| Kurbantay|Nazuk|N| You|Li|L| Upur|Halmurat|H|

Abnormal Savda
abnormal Savda Munziq
rat model
metabonomics
traditional Uyghur medicine


Inflammatory breast cancer clusters: A hypothesis.

Abstract: Cancer clusters have long been a focus of interest because of the possibility of identifying etiologic agents. Only on rare occasions, however, have such cluster investigations been successful. One major difficulty in cluster investigations, particularly in the area of breast cancer, is the long latent period. There have been a number of publications providing a discouraging picture regarding cancer cluster investigations. The possibility of learning from a cluster investigation, however, is greatly increased if the cancer involved is relatively rare and if it has a short latent period. Inflammatory breast cancer (IBC) fits these criteria and is worth pursuing because of the strong evidence that environmental factors play a major role. In this report we describe our experience with several clusters and the lessons learned which are now being utilized to improve investigation of future IBC clusters. The first IBC cluster that we evaluated was in 2000, when we were asked to investigate an apparent cluster of IBC in Castro Valley, California where three women in an office setting of 24 people were diagnosed with IBC in a ten month period from May 1999 to March 2000. Our investigation of this striking cluster did not yield a specific trigger for this cluster but it did indicate that the women involved all had at least two IBC risk factors that may well have made them susceptible to getting IBC. We are now investigating another apparent cluster in Texas and are aware of several others requiring careful consideration. We see a need for a consistent protocol for the evaluation of IBC clusters focusing on the laboratory investigation of environmental triggers, primarily infectious agents and chemical carcinogens.

Levine|Paul H|PH|
Hashmi|Salman|S|
Minaei|Ashley A|AA|
Veneroso|Carmela|C|

Inflammatory breast cancer
Environmental
Infectious agents
Toxins


Cortisol, salivary alpha-amylase and children's perceptions of their social networks.

Abstract: In recent years there has been a growing interest in the use of social network analysis in biobehavioral research. Despite the well-established importance of social relationships in influencing human behavior and health, little is known about how children's perception of their immediate social relationships correlates with biological parameters of stress. In this study we explore the association between two measures of children's personal social networks, perceived network size and perceived network density, with two biomarkers of stress, cortisol and salivary alpha-amylase. Forty children (mean age = 8.30, min age = 5, and max age = 12) were interviewed to collect information about their friendships and three samples of saliva were collected. Our results show that children characterized by a lower pre-interview cortisol concentration and a lower salivary alpha-amylase reactivity to the interview reported the highest density of friendships. We discuss this result in light of the multisystem approach to the study of children's behavioral outcomes, emphasizing that future work of this kind is needed in order to understand the cognitive and biological mechanisms underlying children's and adolescents' social perceptual biases.

Ponzi|Davide|D|
Muehlenbein|Michael P|MP|
Geary|David C|DC|
Flinn|Mark V|MV|

Cortisol
Salivary alpha-amylase
Personal social networks
Perceptual biases
Psychosocial stress


Cardiac Intervention Improves Heart Disease and Clinical Outcomes in Patients With Muscular Dystrophy in a Multidisciplinary Care Setting.

Abstract: Background Patients with muscular dystrophy (MD) represent a vulnerable patient population with no clearly defined care model in modern-day clinical practice to manage a high burden of heart disease and comorbidities. We demonstrate the effectiveness of cardiac interventions, namely the initiation and optimization of medical and device therapies, as part of a multidisciplinary care approach to improve clinical outcomes in patients with MD. Methods and Results We conducted a prospective cohort study at the Neuromuscular Multidisciplinary clinic following patients with dystrophinopathies, limb-girdle MD, type 1 myotonic dystrophy, and facioscapulohumeral MD. A negative control group classified as non-MD myopathies without heart disease, was also tracked. Our cohort of 185 patients (median age: 42 years; 79 [42.7%] women), included 145 patients with MD. Cardiomyopathy was present in 65.6% of the patients with dystrophinopathies (21 of 32) and 27.3% of the patients with limb-girdle MD (9 of 33). Conduction abnormalities were common in type 1 myotonic dystrophy (33.3% [20/60] patients). Cardiac intervention reversed systolic dysfunction, with left ventricular ejection fraction improving from 43% to 50.0% over a 3-year period. A sustained reduction in healthcare utilization was also observed. The number of outpatient clinic visits decreased from 3.0 to 1.5 visits per year, the duration of hospitalizations was reduced from 14.2 to 0.9 days per year, and the number of cardiac-related hospitalizations decreased from 0.4 to 0.1 hospitalizations per year associated with low mortality. Conclusions Our study demonstrates that cardiac intervention as part of a comprehensive multidisciplinary care approach to treating patients with MD leads to a sustained improvement in clinical outcomes.

Nikhanj|Anish|A|
Yogasundaram|Haran|H|
Miskew Nichols|Bailey|B|
Richman-Eisenstat|Janice|J|
Phan|Cecile|C|
Bakal|Jeffrey A|JA|
Siddiqi|Zaeem A|ZA|
Oudit|Gavin Y|GY|

heart disease
muscular dystrophy
multidisciplinary care
medical therapy
outcome data