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Introduction: There is a resurgence of interest in the therapeutic potential of psychedelic substances such as 3,4-methylenedioxymethamphetamine (MDMA). Primary findings from our randomized, double-blind, placebo-controlled, multi-site Phase 3 clinical trial of participants with severe PTSD (NCT03537014) showed that MDMA-assisted therapy induced significant attenuation in the Clinician-Administered PTSD Scale for DSM-5 compared to Therapy with placebo. Deficits in emotional coping skills and altered self-capacities constitute major obstacles to successful completion of available treatments. The current analysis evaluated the differential effects of MDMA-assisted therapy and Therapy with placebo on 3 transdiagnostic outcome measures and explored the contribution of changes in self-experience to improvement in PTSD scores. Methods: Participants were randomized to receive manualized therapy with either MDMA or placebo during 3 experimental sessions in combination with 3 preparation and 9 integration therapy visits. Symptoms were measured at baseline and 2 months after the last experimental session using the 20-item Toronto Alexithymia Scale (TAS-20), the 26-item Self Compassion Scale (SCS), and the 63-item Inventory of Altered Self-Capacities (IASC). Results: 90 participants were randomized and dosed (MDMA-assisted therapy, n = 46; Therapy with placebo, n = 44); 84.4% (76/90) had histories of developmental trauma, and 87.8% (79/90) had suffered multiple traumas. MDMA-assisted therapy facilitated statistically significant greater improvement on the TAS-20, the SCS, and most IASC factors of interpersonal conflicts; idealization disillusionment; abandonment concerns; identity impairment; self-awareness; susceptibility to influence; affect dysregulation; affect instability; affect skill deficit; tension reduction activities; the only exception was identity diffusion. Conclusion: Compared with Therapy with placebo, MDMA-assisted therapy had significant positive effects on transdiagnostic mental processes of self-experience which are often associated with poor treatment outcome. This provides a possible window into understanding the psychological capacities facilitated by psychedelic agents that may result in significant improvements in PTSD symptomatology. [ABSTRACT FROM AUTHOR]

The clinical application of EDV, a potent antioxidant drug approved for amyotrophic lateral sclerosis (ALS), is limited by its short biological half-life and poor water solubility necessitating hospitalization during intravenous infusion. Nanotechnology-based drug delivery constitutes a powerful tool through inferring drug stability and targeted drug delivery improving drug bioavailability at the diseased site. Nose-to-brain drug delivery offers direct access to the brain bypassing the blood brain barrier and reducing systemic biodistribution. In this study, we designed EDV-loaded poly(lactic- co -glycolic acid) (PLGA)-based polymeric nanoparticles (NP-EDV) for intranasal administration. NPs were formulated by the nanoprecipitation method. Morphology, EDV loading, physicochemical properties, shelf-life stability, in vitro release and pharmacokinetic assessment in mice were conducted. EDV was efficiently loaded into ∼90 nm NPs, stable up to 30 days of storage, at ∼3% drug loading. NP-EDV reduced H 2 O 2 -induced oxidative stress toxicity in mouse microglial cell line BV-2. Optical imaging and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) showed that intranasal delivery of NP-EDV offered higher and more sustained brain uptake of EDV compared to intravenous administration. This study is the first of its kind to develop an ALS drug in a nanoparticulate formulation for nose-to-brain delivery raising hope to ALS patients where currently treatment options are limited to two clinically approved drugs only. [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction: Activated charcoal based compounds such as DOAC‐stop™ (DS) have been developed to remove direct oral anticoagulant (DOAC) interference in‐vitro. However, few studies have used this approach with global coagulation assays (GCAs), such as thrombin generation assays, which are sensitive to the effect of DOACs. Methods: Thrombin generation with and without thrombomodulin (TM) via the automated ST‐Genesia system, and the overall haemostatic potential (OHP) assay, a spectrophotometric fibrin generation assay in which fibrin formation (triggered by small amounts of thrombin (overall coagulation potential, OCP)) and fibrinolysis (by the addition of thrombin and tissue plasminogen activator) were measured on (i) pooled normal plasma (PNP) spiked with varying amounts of rivaroxaban, apixaban, and dabigatran, and (ii) platelet poor plasma (PPP) from 21 non‐anticoagulated adults, before and after DS addition. Results: Following the addition of DS to spiked PNP without thrombomodulin, thrombin and velocity index increased by 21.9% and 42.6%, respectively, while ETP increased by 6.93%. A decrease in OCP (−10.6%) and OHP (−12.7%) was observed following DS. Similar changes were seen post‐DS to plasma from non‐anticoagulated patients. Also in this group, pre‐ and post‐DS thrombin generation parameters showed high correlation, with the strongest observed for ETP (R2 = 0.94). There was a strong correlation for OHP parameters, with the closest seen with OCP (R2 = 0.96) and OHP (R2 = 0.95). Conclusion: DS causes some changes to the ETP and OHP assay, however, strong correlations were seen pre‐ and post‐DS in all GCA parameters. These findings support the use of DS to facilitate GCA testing in anticoagulated individuals for evaluation of the underlying thrombotic state. [ABSTRACT FROM AUTHOR]

Intranasal administration is becoming increasingly more attractive as a fast delivery route to the brain for therapeutics circumventing the blood-brain barrier (BBB). Gold nanorods (AuNRs) demonstrate unique optical and biological properties compared to other gold nanostructures due to their high aspect ratio. In this study, we investigated for the first time the brain region-specific distribution of AuNRs and their potential as a drug delivery platform for central nervous system (CNS) therapy following intranasal administration to mice using a battery of analytical and imaging techniques. AuNRs were functionalized with a fluorescent dye (Cyanine5, Cy5) or a metal chelator (diethylenetriaminepentaacetic dianhydride, DTPA anhydride) to complex with Indium-111 via a PEG spacer for optical and nuclear imaging, respectively. Direct quantification of gold was achieved by inductively coupled plasma mass spectrometry. Rapid AuNRs uptake in mice brains was observed within 10 min following intranasal administration which gradually reduced over time. This was confirmed by the 3 imaging/analytical techniques. Autoradiography of sagittal brain sections suggested entry to the brain via the olfactory bulb followed by diffusion to other brain regions within 1 h of administration. The presence of AuNR in glioblastoma (GBM) tumors following intranasal administration was also proven which opens doors for AuNRs applications, as nose-to-brain drug delivery carriers, for treatment of a range of CNS diseases. [Display omitted] • Multi-modal imaging techniques were applied to understand the spatiotemporal biodistribution of gold nanorods. • Gold nanorods demonstrated rapid brain uptake following intranasal administration. • Gold nanorods first reached olfactory bulbs within minutes and gradually distributed to other brain regions with time. [ABSTRACT FROM AUTHOR]

Abnormal coagulation and fibrinolysis contributes to the respiratory distress syndrome in COVID-19. We aimed to explore the association of impaired fibrinolytic potential with disease severity and oxygen requirement in hospitalized patients. Adults admitted to hospital with confirmed COVID-19 infection between 1–31 January 2022 were included, corresponding to the first Omicron outbreak in Melbourne, Victoria. The first citrated plasma sample requested within 24 h of the patient's presentation was obtained and analyzed by the overall hemostatic potential (OHP) assay, a spectrophotometric assay in which fibrin formation (triggered by small amounts of thrombin (OCP)) and fibrinolysis (by the addition of thrombin and tissue plasminogen activator (OHP and OFP%)) were simultaneously measured. There were 266 patients (median 72 years, 52.9% male), of which 49.6% did not require oxygen therapy. COVID-19 severity and requirement for oxygen was significantly associated with higher OCP, OHP, and lower OFP%. Vaccinated individuals compared with non-vaccinated individuals had significantly lower OHP (16.5 vs. 23.1, p = 0.015) and higher OFP (72.0% vs. 65.1%, p = 0.005), as well as significantly lower AST, ferritin, LDH, CRP, and D-dimer. A multivariate model containing OHP was constructed with the outcome of oxygen requirement, with c-statistic of 0.85 (95%CI 0.81–0.90). In this pilot study, we show a significant correlation between OHP results and requirement for oxygen supplementation in hospitalized patients during a period dominated by the Omicron variant. The results were incorporated into a multivariate model that predicted for oxygen requirement, with high discriminative ability. [ABSTRACT FROM AUTHOR]

Eating disorders (EDs) and posttraumatic stress disorder (PTSD) are highly comorbid, yet there are no proven integrative treatment modalities for ED-PTSD. In clinical trials, MDMA-assisted therapy (MDMA-AT) has shown marked success in the treatment of PTSD and may be promising for ED-PTSD. Ninety individuals with severe PTSD received treatment in a double-blind, placebo-controlled pivotal trial of MDMA-AT. In addition to the primary (Clinician-Administered PTSD Scale) and secondary (Sheehan Disability Scale) outcome measures, the Eating Attitudes Test 26 (EAT-26) was administered for pre-specified exploratory purposes at baseline and at study termination. The study sample consisted of 58 females (placebo = 31, MDMA = 27) and 31 males (placebo = 12, MDMA = 19) (n = 89). Seven participants discontinued prior to study termination. At baseline, 13 (15%) of the 89 individuals with PTSD had total EAT-26 scores in the clinical range (≥20), and 28 (31.5%) had total EAT-26 scores in the high-risk range (≥11) despite the absence of active purging or low weight. In completers (n = 82), there was a significant reduction in total EAT-26 scores in the total group of PTSD participants following MDMA-AT versus placebo (p =.03). There were also significant reductions in total EAT-26 scores in women with high EAT-26 scores ≥11 and ≥ 20 following MDMA-AT versus placebo (p =.0012 and p =.0478, respectively). ED psychopathology is common in individuals with PTSD even in the absence of EDs with active purging and low weight. MDMA-AT significantly reduced ED symptoms compared to therapy with placebo among participants with severe PTSD. MDMA-AT for ED-PTSD appears promising and requires further study. [ABSTRACT FROM AUTHOR]

PURPOSE OF THE STUDY: To characterize the postacute sequalae of severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) infection (PASC) in children. STUDY POPULATION: 659 286 patients younger than 21 years of age who underwent testing for SARS-CoV-2 antigen or PCR between March 1, 2020 and October 31, 2021. All patients were part of the National Institutes of Health Researching COVID to Enhance Recovery (RECOVER) Initiative. METHODS: Syndromic, systemic, and medication PASC characteristics were obtained from retrospective chart review using International Classification of Diseases, 10th Edition codes of electronic health data data. Outcomes were assessed in patients 28 to 179 days after cohort entrance or December 31, 2021, whichever came first. Adjusted hazard ratios (aHRs) were obtained for PASC features of patients who tested positive compared with those who tested negative for SARS-CoV-2. RESULTS: The cohort consisted of 348 091 (52.8%) males, with a mean (SD) age of 8.1 (5.7) years. Of participants, 59 893 (9.1%) tested positive for SARS-CoV-2, whereas 599 393 (90.9%) tested negative, and PASC data were obtained between four to five months following initial test date. Those with test positivity were more likely to be non-Hispanic Black (20.2% vs 15.4%), Hispanic (18.8% vs 15.3%), and older (16 to younger than 21 years, 17.4% vs 12.1%). Most common syndrome and systemic PASC features included loss of smell (aHR 1.96, 95% confidence interval [CI], 1.16-3.32), and myocarditis (aHR, 3.10; 95% CI, 1.94-4.96), respectively. The most commonly used medication included cough or cold preparations. Compared with those with negative tests, participants with positive tests had an incidence proportion difference of 3.7% (95% CI, 3.2-4.2) for having at least one syndromic, systemic, or medication PASC feature. Proportional hazards models showed the highest rate of any PASC feature in children younger than 5 years of age, those with complex chronic medical history, and those who received ICU level of care during acute SARS-CoV-2 infection. CONCLUSIONS: Compared with adult studies, the burden of PASC in children may be low. The incidence proportion difference of PASC features between those who tested positive versus negative was 3.7%. Factors associated with an increased risk of PASC included young age, comorbid medical complexity, and acute illness severity. [ABSTRACT FROM AUTHOR]

PURPOSE OF THE STUDY: To analyze patterns of neutralizing antibodies in children and adolescents following mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections STUDY POPULATION: One hundred twenty six participants aged 0 to 16 years with confirmed SARS-CoV-2 infection by nasopharyngeal-polymerase chain reactions. All participants were followed at KK Women's Children's Hospital in Singapore from February 1, 2020 to September 30, 2021. METHODS: Participant blood samples were obtained at various time points up to 16 months after SARS- CoV-2 infection. Neutralizing antibodies were measured using inhibition enzyme-linked immunosorbent assay. Variables including age, sex, and symptom status were adjusted when analyzing temporal distribution of neutralizing antibody levels. RESULTS: Mean age of 126 participants was 7.4 years (1 month-16 years), with 74 male (58.7%) and 52 female (41.3%). All symptomatic cases were mild (91 patients or 72%). Peak neutralizing antibody levels were seen 1 to 3 months after infection (median value of 84% via surrogate virus neutralization test) and remained high at 9 to 13 months after infection. After adjusting for sex and symptom status, neutralizing antibody levels were highest in those <5 years of age (71.6%; 95% confidence interval, 58.5%-84.6%) during the acute phase of infection (<1 month), with little change at the end of the study. During the acute phase of infection, those in the 12 to 16 years group had the lowest antibody levels, which peaked at 1 to 3 months after infection. CONCLUSIONS: Neutralizing SARS-CoV-2 antibodies may persist up to 16 months in children and adolescents following a positive polymerase chain reaction-nasopharyngeal test. Younger children <5 years of age especially had rapid production of neutralizing antibodies and maintained their levels over time, compared with older participants of the study. [ABSTRACT FROM AUTHOR]

PURPOSE OF THE STUDY: To examine the effect of neighborhood-level socioeconomic factors on childhood wheeze and asthma. STUDY POPULATION: There were 5809 children enrolled in the Children's Respiratory and Environmental Workgroup birth cohort. METHODS: Census information of Children's Respiratory and Environmental Workgroup participants were obtained using the Decentralized Geomarker Assessment for Multisite Studies approach. Asthma incidence was obtained from caregiver report of physician diagnosis. Early wheeze and persistent wheeze were defined per caregiver reported information (early: wheeze at 1-2 years, persistent: up to 4 years with at least 1 episode between 5-11 years). Hazard ratios of asthma incidence and odds ratios of wheeze prevalence were determined for factors including maternal education, maternal smoking history during pregnancy, and parental history of asthma. RESULTS: Overall prevalence of early and persistent wheeze were 46% and 26%, respectively. Asthma prevalence by 11 years of age had a median prevalence of 25%. Factors associated with increased hazard ratio (HR) of asthma included race (HR 1.47; 95% confidence interval, 1.26-1.73 for Black children and HR 1.29; 95% confidence interval, 1.09-1.53 for Hispanic children), low income-household, poverty, population density, and parental history of asthma. Similar findings were seen for early and persistent wheeze. Even after adjusting for census variables such as household income, race and ethnicity persisted as risk factors for increased risk of asthma and/or wheeze. CONCLUSIONS: Factors associated with asthma and wheeze included neighborhood socioeconomic factors, race, and ethnicity. Risk for asthma and wheeze remained higher for Black and Hispanic children compared with white children, even after adjusting for neighborhood factors such as poverty and household income. These results reflect structural and social determinants of health that can adversely affect the care of Black and Hispanic children. [ABSTRACT FROM AUTHOR]

In M. Ru and P. Vojta, A birational Nevanlinna constant and its consequences, Amer. J. Math.142(3) (2020) 957–991, among other things, proved the so-called general theorem (arithmetic part) which can be viewed as an extension of Schmidt's subspace theorem. In this paper, we extend their result by replacing the divisors by closed subschemes. [ABSTRACT FROM AUTHOR]

This paper reports the use of a self‐assembling hydrogel as a delivery vehicle for the Parkinson's disease drug l‐DOPA. Based on a two‐component combination of an l‐glutamine amide derivative and benzaldehyde, this gel has very soft rheological properties and self‐healing characteristics. It is demonstrated that the gel can be formulated to encapsulate l‐DOPA. These drug‐loaded gels are characterized, and rapid release of the drug is obtained from the gel network. This drug‐loaded hydrogel has appropriate rheological characteristics to be amenable for injection. This system is therefore tested as a vehicle for nasal delivery of neurologically‐active drugs—a drug delivery strategy that can potentially avoid first pass liver metabolism and bypass the blood–brain barrier, hence enhancing brain uptake. In vitro tests indicate that the gel has biocompatibility with respect to nasal epithelial cells. Furthermore, animal studies demonstrate that the nasal delivery of a gel loaded with 3H‐labeled l‐DOPA out‐performed a simple intranasal l‐DOPA solution. This is attributed to longer residence times of the gel in the nasal cavity resulting in increased blood and brain concentrations. It is demonstrated that the likely routes of brain penetration of intranasally‐delivered l‐DOPA gel involve the trigeminal and olfactory nerves connecting to other brain regions. [ABSTRACT FROM AUTHOR]

Immunotherapy is currently a standard of care in the treatment of many malignancies. However, predictable side effects caused by systemic administration of highly immunostimulatory molecules have been a serious concern within this field. Intratumoural expression or silencing of immunogenic and immunoinhibitory molecules using nucleic acid-based approaches such as plasmid DNA (pDNA) and small interfering RNA (siRNA), respectively, could represent a next generation of cancer immunotherapy. Here, we employed lipid nanoparticles (LNPs) to deliver either non-specific pDNA and siRNA, or constructs targeting two prominent immunotherapeutic targets OX40L and indoleamine 2,3-dioxygenase-1 (IDO), to tumours in vivo. In the B16F10 mouse model, intratumoural delivery of LNP-formulated non-specific pDNA and siRNA led to strong local immune activation and tumour growth inhibition even at low doses due to the pDNA immunogenic nature. Replacement of these non-specific constructs by pOX40L and siIDO resulted in more prominent immune activation as evidenced by increased immune cell infiltration in tumours and tumour-draining lymph nodes. Consistently, pOX40L alone or in combination with siIDO could prolong overall survival, resulting in complete tumour regression and the formation of immunological memory in tumour rechallenge models. Our results suggest that intratumoural administration of LNP-formulated pDNA and siRNA offers a promising approach for cancer immunotherapy. [Display omitted] • I.t injection of non-specific LNPs led to strong local immune activation and tumour growth inhibition even at low doses. • pOX40L + siIDO LNPs induced more prominent immune activation than non-specific pDNA+siRNA LNPs. • pOX40L or pOX40L + siIDO LNPs prolonged survival, led to complete tumour regression and immunological memory generation. • I.t injection of LNP-formulated pDNA and siRNA offers a promising approach for cancer immunotherapy. [ABSTRACT FROM AUTHOR]

We establish consequences of the moving form of Schmidt's Subspace Theorem. Indeed, we obtain inequalities that bound the logarithmic greatest common divisor of moving multivariable polynomials evaluated at moving S-unit arguments. In doing so, we complement recent work of Levin. As an additional application, we obtain results that pertain to the greatest common divisor problem for algebraic linear recurrence sequences. These observations are motivated by previous related works of Corvaja-Zannier, Levin, and others. [ABSTRACT FROM AUTHOR]

We study upper bounds for the counting function of common zeros of two meromorphic functions in various contexts. The proofs and results are inspired by recent work involving greatest common divisors in Diophantine approximation, to which we introduce additional techniques to take advantage of the stronger inequalities available in Nevanlinna theory. In particular, we prove a general version of a conjectural "asymptotic gcd" inequality of Pasten and the second author, and consider moving targets versions of our results. [ABSTRACT FROM AUTHOR]

Apoptotic cells and cell fragments, especially those produced as a result of immunogenic cell death (ICD), are known to be a potential source of cancer vaccine immunogen. However, due to variation between tumours and between individuals, methods to generate such preparations may require extensive ex vivo personalisation. To address this, we have utilised the concept of in situ vaccination whereby an ICD inducing drug is injected locally to generate immunogenic apoptotic fragments/cells. These fragments are then adjuvanted by a co-administered cell reactive CpG adjuvant. We first evaluate means of labelling tumour cells with CpG adjuvant, we then go on to demonstrate in vitro that labelling is preserved following apoptosis and, furthermore, that the apoptotic body-adjuvant complexes are readily transferred to macrophages. In in vivo studies we observe synergistic tumour growth delays and elevated levels of CD4+ and CD8+ cells in tumours receiving adjuvant drug combination. CD4+/CD8+ cells are likewise elevated in the tumour draining lymph node and activated to a greater extent than individual treatments. This study represents the first steps toward the evaluation of rationally formulated drug-adjuvant combinations for in situ chemo-immunotherapy. Unlabelled Image [ABSTRACT FROM AUTHOR]

Radiotherapy is a cancer treatment utilising high doses of ionizing radiation to destroy cancer cells. Our team has pioneered neutron activation of 152Sm, filled and sealed into single-walled (SWCNTs) and multi-walled carbon nanotubes (MWCNTs), to create stable and high-dose radioactive carbon nanocapsules for cancer radiotherapy. In this work, MWCNTs filled with enriched 152SmCl 3 (Sm@MWCNTs) were sealed and irradiated, followed by surface functionalisation with an epidermal growth factor receptor (EGFR)-targeting antibody. Characterisation of functionalised Sm@MWCNTs was carried out using thermogravimetric analysis, gel electrophoresis and transmission electron microscopy. The organ biodistribution of the radioactive functionalised 153Sm@MWCNTs and therapeutic efficacy were studied in an experimental melanoma lung metastatic tumour model in mice after intravenous injection. Quantitative biodistribution analyses showed high accumulation of 153Sm@MWCNT-Ab in lung. Significant tumour growth reduction was induced by both treatments of 153Sm@MWCNTs functionalised with or without the antibody after a single intravenous injection. Although EGFR targeting showed no improvement in therapeutic efficacy, reduced spleen toxicity and normal haematological profiles were obtained for both functionalised derivatives. The current study demonstrated the possibility of performing chemical functionalisation and antibody conjugation on radioactive nanocapsules post-irradiation for the preparation of targeted radiopharmaceuticals. Image 1 [ABSTRACT FROM AUTHOR]

Let f and g be algebraically independent entire functions. We first give an estimate of the Nevanlinna counting function for the common zeros of fn-1 and gn-1 for sufficiently large n. We then apply this estimate to study divisible sequences in the sense that fn - 1 is divisible by gn - 1 for infinitely many n. For the first part of establishing our gcd estimate, we need tof ormulate a truncated second main theorem for effective divisors by modifying a theorem from a paper by Hussein and Ru and explicitly computing the constants involved for a blowup of P¹ ×P¹ along a point with its canonical divisor and the pull-back of vertical and horizontal divisors of P¹ × P¹. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract The inability of traditional chemotherapeutics to reach cancer tissue reduces the treatment efficacy and leads to adverse effects. A multifunctional nanovector was developed consisting of porous silicon, superparamagnetic iron oxide, calcium carbonate, doxorubicin and polyethylene glycol. The particles integrate magnetic properties with the capacity to retain drug molecules inside the pore matrix at neutral pH to facilitate drug delivery to tumor tissues. The MRI applicability and pH controlled drug release were examined in vitro together with in-depth material characterization. The in vivo biodistribution and compound safety were verified using A549 lung cancer bearing mice before proceeding to therapeutic experiments using CT26 cancer implanted mice. Loading doxorubicin into the porous nanoparticle negated the adverse side effects encountered after intravenous administration highlighting the particles' excellent biocompatibility. Furthermore, the multifunctional nanovector induced 77% tumor reduction after intratumoral injection. The anti-tumor effect was comparable with that of free doxorubicin but with significantly alleviated unwanted effects. These results demonstrate that the developed porous silicon-based nanoparticles represent promising multifunctional drug delivery vectors for cancer monitoring and therapy. [ABSTRACT FROM AUTHOR]

E-cigarettes are promoted as healthier alternatives to conventional cigarettes. Many cigarette smokers use both products. It is unknown whether the additional use of e-cigarettes among cigarette smokers (dual users) is associated with reduced exposure to tobacco-related health risks. Cross-sectional analysis was performed using baseline data from the Health eHeart Study, among English-speaking adults, mostly from the United States. Cigarette use (# cigarettes/day) and/or e-cigarette use (# days, # cartridges, and # puffs) were compared between cigarette only users vs. dual users. Additionally, we examined cardiopulmonary symptoms/ conditions across product use: no product (neither), e-cigarettes only, cigarettes only, and dual use. Among 39,747 participants, 573 (1.4%) reported e-cigarette only use, 1,693 (4.3%) reported cigarette only use, and 514 (1.3%) dual use. Dual users, compared to cigarette only users, reported a greater median (IQR) number of cigarettes per day, 10.0 (4.0–20.0) vs. 9.0 (3.0–15.0) (p < .0001), a lower (worse) median (IQR) SF-12 general health score, 3.3 (2.8–3.8) vs. 3.5 (2.8–3.9) (p = .0014), and a higher (worse) median (IQR) breathing difficulty score in the past month, 2.0 (1.0–2.0) vs. 1.0 (1.0–2.0) (p = .001). Of the 19 cardiopulmonary symptoms/ conditions, having a history of arrhythmia was significantly different between cigarette only users (14.2%) and dual users (17.8%) (p = .02). In this sample, dual use was not associated with reduced exposure to either (i) cigarettes, compared to cigarette only users or (ii) e-cigarettes, compared to e-cigarette only users. E-cigarette only use, compared to no product use, was associated with lower general health scores, higher breathing difficulty scores (typically and past month), and greater proportions of those who responded ‘yes’ to having chest pain, palpitations, coronary heart disease, arrhythmia, COPD, and asthma. These data suggest the added use of e-cigarettes alone may have contributed to cardiopulmonary health risks particularly respiratory health risks. [ABSTRACT FROM AUTHOR]

The article provides information on this synopsis book which offers reviews on allergy and immunology topics and aims to increase understanding and advance management of allergic and immunologic disorders impacting children.

Background: Depressive symptoms can lower adherence and change in dietary studies. Behavioral activation may reduce these effects.Purpose: This study aims to assess relationships among depressive symptoms on adherence and dietary change in the Women's Healthy Eating and Living (WHEL) StudyMethods: Secondary analyses from the WHEL Study, which achieved major dietary change in breast cancer survivors (N = 2817), were conducted. Logistic regressions were undertaken of baseline depressive symptoms (six-item Center for Epidemiologic Studies Depression Scale (CES-D)) with (1) completion of 1- and 4-year study assessments and (2) validated change in dietary behavior in the intervention group.Results: In the comparison group (vs. intervention), depressive symptoms lowered completion of dietary recalls and clinic visits [4 years: odds ratio (OR) = 2.0; 95 % confidence interval (CI) = 1.4-3.0]. The behaviorally oriented intervention achieved major change in those furthest from study targets, although changes were lower in those with depressive symptoms: fruit/vegetable (+37.2 %), fiber (+49.0 %), and fat (-22.4 %).Conclusions: Behavioral activation in dietary change interventions can overcome the impact of depressive symptoms. [ABSTRACT FROM AUTHOR]

Abstract: Food allergy is increasingly common in children, affecting about 4%‐8%. The mainstays of management remain allergen avoidance and emergency preparedness to treat allergic reactions with emergency medications. Unfortunately, these approaches are unsatisfactory for many patients and their families as the restrictions, constant vigilance, and unpredictable severity of allergic reactions negatively impact quality of life. In recent decades, there has been significant interest in developing treatments for food allergy that lead to desensitization to increase thresholds for triggering allergic reactions and decrease the risk of reacting to allergen‐contaminated food products. Epicutaneous immunotherapy (EPIT) is a novel therapy that is currently under investigation, delivering allergen via repeated applications to the skin and targeting antigen‐presenting cells in the superficial skin layers. Murine models have demonstrated that allergen uptake is an active process by skin dendritic cells with subsequent migration to draining lymph nodes. Allergen exposure to the non‐vascularized epidermis limits systemic absorption, contributing to the high‐safety profile. Results from murine experiments showed that EPIT has comparable efficacy as subcutaneous immunotherapy in terms of challenge outcomes, airway hyper‐responsiveness, and immunologic parameters. Several clinical trials of EPIT have recently been completed or are ongoing. Results support the high safety and tolerability of this approach. Efficacy data suggest that the change in threshold eliciting dose following 1 year of therapy is less than that seen compared to high‐dose (2‐4 g peanut protein) oral immunotherapy, but more prolonged treatment with EPIT appears to lead to increasing desensitization. Additional data from larger‐scale studies should provide a more robust assessment of safety and efficacy of EPIT. [ABSTRACT FROM AUTHOR]

We give a natural sufficient condition which ensures the finiteness of the number of integral points on a projective space omitting finitely many hyperplanes defined over a one-dimensional function field of positive characteristic. In this setting, when the number of hyperplanes is 2 n + 2 , where n is the dimension of the ambient projective space, we use this natural condition to explain and sharpen an earlier result of the second named author, which provides a concrete condition on the coefficients of the linear forms producing hyperplanes such that the above finiteness property is satisfied. [ABSTRACT FROM AUTHOR]

Nitrogen containing bisphosphonates (N-BPs) including zoledronate (ZOL) and alendronate (ALD) inhibit farnesyl diphosphate synthase, and have been shown to have a cytotoxic affect against cancer cells as a monotherapy and to also sensitise tumour cells to destruction by γδ T cells. γδ T cells are a subset of human T lymphocytes and have a diverse range of roles in the immune system including the recognition and destruction of cancer cells. This property of γδ T cells can be harnessed for use in cancer immunotherapy through in vivo expansion or the adoptive transfer of ex vivo activated γδ T cells. The use of N-BPs with γδ T cells has been shown to have a synergistic effect in in vitro , animal and clinical studies. N-BPs have limited in vivo activity due to rapid clearance from the circulation. By encapsulating N-BPs in liposomes (L) it is possible to increase the levels of N-BPs at non-osseous tumour sites. L-ZOL and L-ALD have been shown to have different toxicological profiles than free ZOL or ALD. Both L-ALD and L-ZOL led to increased spleen weight, leucocytosis, neutrophilia and lymphocytopenia in mice after intravenous injection. L-ALD was shown to be better tolerated than L-ZOL in murine studies. Biodistribution studies have been performed in order to better understand the interaction of N-BPs and γδ T cells in vivo . Additionally, in vivo therapy studies have shown that mice treated with both L-ALD and γδ T cells had a significant reduction in tumour growth compared to mice treated with L-ALD or γδ T cells alone. The use of ligand-targeted liposomes may further increase the efficacy of this combinatory immunotherapy. Liposomes targeting the αvβ6 integrin receptor using the peptide A20FMDV2 had a greater ability than untargeted liposomes in sensitising cancer cells to destruction by γδ T cells in αvβ6 positive cancer cell lines. [ABSTRACT FROM AUTHOR]

The apnea hypopnea index (AHI) reported by positive airway pressure (PAP) device is widely used in clinical practice, yet its correlation with standardized AHI obtained during the sleep study is not established. The current study was conducted to investigate the correlation between AHI estimated by the PAP device and reported on the smart card with the AHI found during the PAP polysomnography (PSG) in the “real world” setting at an academic sleep center. We retrospectively reviewed the medical records of 280 patients who underwent a PAP titration PSG at Drexel sleep center, and were later prescribed a PAP device. The AHI was categorized in clinically relevant subgroups (as AHI ≤5 and AHI >5). The AHI at the final pressure on the PSG and the average AHI from the prescribed PAP device were compared. The results showed that in the majority (77.3%) of patients (126 of 163), the AHI from both PAP device and PSG correlated well and were in the same category (AHI ≤5 and AHI >5 respectively). The majority of patients (80.7%) with PSG AHI of <5 had PAP device AHI <5 as well. By contrast, if PSG AHI was >5, 61.5% patients reported good control, with AHI <5 on PAP device AHI. We conclude that in a majority of patients who were optimally titrated in the sleep laboratory, the PAP device continued to show optimal control at home. [ABSTRACT FROM AUTHOR]

Hepatitis B Virus core (HBc) particles have been studied for their potential as drug delivery vehicles for cancer therapy. HBc particles are hollow nano-particles of 30–34 nm diameter and 7 nm thick envelopes, consisting of 180–240 units of 21 kDa core monomers. They have the capacity to assemble/dis-assemble in a controlled manner allowing encapsulation of various drugs and other biomolecules. Moreover, other functional motifs, i.e. receptors, receptor binding sequences, peptides and proteins can be expressed. This study focuses on the development of genetically modified HBc particles to specifically recognise and target human epidermal growth factor receptor-2 (HER2)-expressing cancer cells, in vitro and in vivo , for future cancer therapy. The non-specific binding capacity of wild type HBc particles was reduced by genetic deletion of the sequence encoding arginine-rich domains. A specific HER2-targeting was achieved by expressing the Z HER2 affibodies on the HBc particles surface. In vitro studies showed specific uptake of Z HER2 -ΔHBc particles in HER2 expressing cancer cells. In vivo studies confirmed positive uptake of Z HER2 -ΔHBc particles in HER2-expressing tumours, compared to non-targeted ΔHBc particles in intraperitoneal tumour-bearing mice models. The present results highlight the potential of these nanocarriers in targeting HER2-positive metastatic abdominal cancer following intra-peritoneal administration. [ABSTRACT FROM AUTHOR]

Anaphylaxis is a potentially life-threatening, severe allergic reaction. The immediate assessment of patients having an allergic reaction and prompt administration of epinephrine, if criteria for anaphylaxis are met, promote optimal outcomes. National and international guidelines for the management of anaphylaxis, including those for management of allergic reactions at school, as well as several clinical reports from the American Academy of Pediatrics, recommend the provision of written emergency action plans to those at risk of anaphylaxis, in addition to the prescription of epinephrine autoinjectors. This clinical report provides information to help health care providers understand the role of a written, personalized allergy and anaphylaxis emergency plan to enhance the care of children at risk of allergic reactions, including anaphylaxis. This report offers a comprehensive written plan, with advice on individualizing instructions to suit specific patient circumstances. [ABSTRACT FROM AUTHOR]

Weconsider the problem giving upper bounds for the counting function of common zeros (i.e., the gcd) of two entire analytic functions in various settings. Applying techniques from analytic number theory and Diophantine approximation in the context of entire and meromorphic functions, we establish bounds of this type covering several aspects that were not well suited for the previously used methods in the context of this problem. [ABSTRACT FROM AUTHOR]

Magnetic drug targeting has been proposed as means of concentrating therapeutic agents at a target site and the success of this approach has been demonstrated in a number of studies. However, the behavior of magnetic carriers in blood vessels and tumor microcirculation still remains unclear. In this work, we utilized polymeric magnetic nanocapsules ( m -NCs) for magnetic targeting in tumors and dynamically visualized them within blood vessels and tumor tissues before, during and after magnetic field exposure using fibered confocal fluorescence microscopy (FCFM). Our results suggested that the distribution of m-NCs within tumor vasculature changed dramatically, but in a reversible way, upon application and removal of a magnetic field. The m-NCs were concentrated and stayed as clusters near a blood vessel wall when tumors were exposed to a magnetic field but without rupturing the blood vessel. The obtained FCFM images provided in vivo in situ microvascular observations of m-NCs upon magnetic targeting with high spatial resolution but minimally invasive surgical procedures. This proof-of-concept descriptive study in mice is envisaged to track and quantify nanoparticles in vivo in a non-invasive manner at microscopic resolution. [ABSTRACT FROM AUTHOR]

Background: Medical marijuana legalization is associated with a higher prevalence of marijuana use which may affect cigarette use and nicotine dependence in co-users. In the present study, we examined relationships between statewide legalization of medical marijuana and prevalence of cigarette and marijuana co-use and nicotine dependence in co-using adolescents and adults.Methods: Data were analyzed from the 2013 National Survey on Drug Use and Health. We compared cigarette and marijuana co-use in the past 30days across age categories (12-64 years) by statewide medical marijuana legalization. Logistic regression models were used to estimate the odds of having nicotine dependence among current cigarette smokers who also reported past 30-day marijuana use and "ever but not current" marijuana use (vs. "never" use) adjusting for covariates including statewide legalization of medical marijuana.Results: Overall, 5.1% of the sample reported past 30-day cigarette and marijuana co-use and a higher proportion of co-users resided in states where medical marijuana was legal compared to illegal (5.8% vs. 4.8%; p=0.0011). Co-use was associated with greater odds of having nicotine dependence compared to cigarette-only use across age categories. Odds were highest and up to 3-times higher in adolescents aged 12-17 years (OR=3.54; 95%CI: 1.81-6.92) and adults aged 50-64 years (OR=3.08; CI: 1.45-6.55).Conclusion: Marijuana policy could inadvertently affect cigarette and marijuana co-use and pose challenges to tobacco cessation. [ABSTRACT FROM AUTHOR]

Tumour-targeted near-infrared (NIR) optical imaging is an emerging tool for the detection of malignant tissues. This modality can be useful in both diagnosis and intraoperative visualisation, to help defining tumour margins and allow a more precise removal of all the cancerous mass during surgery. In this context, we have developed a series of NIR fluorescent probes that target the prostate-specific membrane antigen (PSMA), an established biomarker overexpressed in prostate cancer. Four new NIR imaging agents were prepared by conjugating the well-known urea-based PSMA targeting module to the NIR fluorophore Cy7.5, with linkers of 7, 10, 17 and 24 atoms. The affinity of each probe for PSMA was assessed through competitive binding and IC 50 measurement in prostate cancer cells, using a previously reported PSMA-targeted NIR probe (i.e. PSMA-IRDye800CW) as reference. The NIR probe PSMA-Cy7.5_2 demonstrated a high affinity for PSMA (i.e. IC 50 = 58.8 nM) and was further studied in mouse xenograft models of prostate cancer, to assess its ability to image PSMA positive tumour tissues. While PSMA-Cy7.5_2 out-performed PSMA-IRDye800CW in vitro , its tumour accumulation in vivo was not as evident. Further micellar aggregation studies indicated that the relatively higher hydrophobic property of PSMA-Cy7.5_2 may lower its bioavailability and tissue distribution following systemic injection, limiting its ability of targeting PSMA tumour in vivo. Nevertheless, the excellent binding capability of PSMA-Cy7.5_2 renders this probe a valid lead for further structural optimisation to develop imaging analogues with high affinity and specificity for PSMA, as required for effective NIR fluorescence-guided applications pre-clinically and clinically. [Display omitted] • Synthesis of new prostate-specific membrane antigen (PSMA) targeted imaging probes. • Identification of a near-infrared (NIR) probe with high binding affinity for PSMA. • Prostate cancer xenograft models to assess distribution to the tumour via imaging. • Micellar aggregation studies to clarify bioavailability and biodistribution in vivo. [ABSTRACT FROM AUTHOR]

The article highlights several studies on the diagnosis and treatment of children with allergy and immunologic diseases. Topics mentioned include the safety of topical corticosteroids, the risk of peanut allergy to infants, allergy to penicillin, the management of asthma, and the immune response of children against COVID-19.

Brain glioblastoma and neurodegenerative diseases are still largely untreated due to the inability of most drugs to cross the blood–brain barrier (BBB). Nanoparticles have emerged as promising tools for drug delivery applications to the brain; in particular carbon nanotubes (CNTs) that have shown an intrinsic ability to cross the BBB in vitro and in vivo . Angiopep-2 (ANG), a ligand for the low-density lipoprotein receptor-related protein-1 (LRP1), has also shown promising results as a targeting ligand for brain delivery using nanoparticles (NPs). Here, we investigate the ability of ANG-targeted chemically-functionalised multi-walled carbon nanotubes ( f -MWNTs) to cross the BBB in vitro and in vivo . ANG was conjugated to wide and thin f -MWNTs creating w -MWNT-ANG and t -MWNT-ANG, respectively. All f -MWNTs were radiolabelled to facilitate quantitative analyses by γ-scintigraphy. ANG conjugation to f -MWNTs enhanced BBB transport of w - and t -MWNTs-ANG compared to their non-targeted equivalents using an in vitro co-cultured BBB model consisting of primary porcine brain endothelial cells (PBEC) and primary rat astrocytes. Additionally, following intravenous administration w -MWNTs-ANG showed significantly higher whole brain uptake than the non-targeted w -MWNT in vivo reaching ~ 2% injected dose per g of brain (%ID/g) within the first hour post-injection. Furthermore, using a syngeneic glioma model, w -MWNT-ANG showed enhanced uptake in glioma brain compared to normal brain at 24 h post-injection. t -MWNTs-ANG, on the other hand, showed higher brain accumulation than w -MWNTs. However, no significant differences were observed between t -MWNT and t -MWNT-ANG indicating the importance of f -MWNTs diameter towards their brain accumulation. The inherent brain accumulation ability of f -MWNTs coupled with improved brain-targeting by ANG favours the future clinical applications of f -MWNT-ANG to deliver active therapeutics for brain glioma therapy. [ABSTRACT FROM AUTHOR]

The articles presents a study on the effects of long-term medical marijuana legalization on cigarette co-use in a sample of adult smokers. It discusses the implication of medical marijuana legalization to cigarette co-use amid the correlation between marijuana and cigarette co-use, the marijuana use as well as nicotine dependence among adult cigarette smokers and the social norms about marijuana.

Earlier studies proved the success of using chemically functionalised multi-walled carbon nanotubes ( f -MWNTs) as nanocarriers to the brain. Little insight into the kinetics of brain distribution of f -MWNTs in vivo has been reported. This study employed a wide range of qualitative and quantitative techniques with the aim of shedding the light on f -MWNT's brain distribution following intravenous injection. γ-Scintigraphy quantified the uptake of studied radiolabelled f -MWNT in the whole brain parenchyma and capillaries while 3D-single photon emission computed tomography/computed tomography imaging and autoradiography illustrated spatial distribution within various brain regions. Raman and multiphoton luminescence together with transmission electron microscopy confirmed the presence of intact f -MWNT in mouse brain, in a label-free manner. The results evidenced the presence of f -MWNT in mice brain parenchyma, in addition to brain endothelium. Such information on the rate and extent of regional and cellular brain distribution is needed before further implementation into neurological therapeutics can be made. [ABSTRACT FROM AUTHOR]

Background: Although vascular smooth muscle cell (VSMC) proliferation is implicated in atherogenesis, VSMCs in advanced plaques and cultured from plaques show evidence of VSMC senescence and DNA damage. In particular, plaque VSMCs show shortening of telomeres, which can directly induce senescence. Senescence can have multiple effects on plaque development and morphology; however, the consequences of VSMC senescence or the mechanisms underlying VSMC senescence in atherosclerosis are mostly unknown.Methods and Results: We examined the expression of proteins that protect telomeres in VSMCs derived from human plaques and normal vessels. Plaque VSMCs showed reduced expression and telomere binding of telomeric repeat-binding factor-2 (TRF2), associated with increased DNA damage. TRF2 expression was regulated by p53-dependent degradation of the TRF2 protein. To examine the functional consequences of loss of TRF2, we expressed TRF2 or a TRF2 functional mutant (T188A) as either gain- or loss-of-function studies in vitro and in apolipoprotein E(-/-) mice. TRF2 overexpression bypassed senescence, reduced DNA damage, and accelerated DNA repair, whereas TRF2(188A) showed opposite effects. Transgenic mice expressing VSMC-specific TRF2(T188A) showed increased atherosclerosis and necrotic core formation in vivo, whereas VSMC-specific TRF2 increased the relative fibrous cap and decreased necrotic core areas. TRF2 protected against atherosclerosis independent of secretion of senescence-associated cytokines.Conclusions: We conclude that plaque VSMC senescence in atherosclerosis is associated with loss of TRF2. VSMC senes cence promotes both atherosclerosis and features of plaque vulnerability, identifying prevention of senescence as a potential target for intervention. [ABSTRACT FROM AUTHOR]

Background: Studies have shown self-monitoring can modify health behaviors, including physical activity (PA). This study tested the utility of a wearable sensor/device (Fitbit® One™; Fitbit Inc., San Francisco, CA) and short message service (SMS) text-messaging prompts to increase PA in overweight and obese adults. Materials and Methods: Sixty-seven adults wore a Fitbit One tracker for 6 weeks; half were randomized to also receive three daily SMS-based PA prompts. The Fitbit One consisted of a wearable tracker for instant feedback on performance and a Web site/mobile application (app) for detailed summaries. Outcome measures were objectively measured steps and minutes of PA by intensity using two accelerometers: Actigraph™ (Pensacola, FL) GT3X+ (primary measure) at baseline and Week 6 and Fitbit One (secondary measure) at baseline and Weeks 1, 2, 3, 4, 5, and 6. Results: Mixed-model repeated-measures analysis of primary measures indicated a significant within-group increase of +4.3 (standard error [SE]=2.0) min/week of moderate- to vigorous-intensity PA (MVPA) at 6-week follow-up (p =0.04) in the comparison group (Fitbit only), but no study group differences across PA levels. Secondary measures indicated the SMS text-messaging effect lasted for only 1 week: the intervention group increased by +1,266 steps (SE=491; p =0.01), +17.8 min/week MVPA (SE=8.5; p =0.04), and +38.3 min/week total PA (SE=15.9; p =0.02) compared with no changes in the comparison group, and these between-group differences were significant for steps (p =0.01), fairly/very active minutes (p <0.01), and total active minutes (p =0.02). Conclusions: These data suggest that the Fitbit One achieved a small increase in MVPA at follow-up and that the SMS-based PA prompts were insufficient in increasing PA beyond 1 week. Future studies can test this intervention in those requiring less help and/or test strategies to increase participants' engagement levels. [ABSTRACT FROM AUTHOR]

• Head CT scans of 101 subjects between 14 and 25 years of age were used to develop a statistical head geometry model. • Skull and scalp statistical geometry models accounts for size and shape variations among the adolescent and young adult population were developed as functions of age, sex, stature, BMI, head circumference, and tragion-to-top distance. • The statistical geometry models account for a high percentage of morphological variations in scalp, outer skull, inner skull, and skull thickness, and may serve as the geometric basis to develop individualized head finite element models for injury assessment and design of head-borne equipment. Modeling the size and shape of human skull and scalp is essential for head injury assessment, design of helmets and head-borne equipment, and many other safety applications. Finite element (FE) head models are important tools to assess injury risks and design personal protective equipment. However, current FE head models are mainly developed based on the midsize male, failing to account for the significant morphological variation that exists in the skull and brain. The objective of this study was to develop a statistical head geometry model that accounts for size and shape variations among the adolescent and young adult population. To represent subject-specific geometry using a homologous mesh, threshold-based segmentation of head CT scans of 101 subjects between 14 and 25 years of age was performed, followed by landmarking, mesh morphing, and projection. Skull and scalp statistical geometry models were then developed as functions of age, sex, stature, BMI, head length, head breadth, and tragion-to-top of head using generalized Procrustes analysis (GPA), principal component analysis (PCA) and multivariate regression analysis. The statistical geometry models account for a high percentage of morphological variations in scalp geometry (R2=0.63), outer skull geometry (R2=0.66), inner skull geometry (R2=0.55), and skull thickness (error < 1 mm) Skull and scalp statistical geometry models accounts for size and shape variations among the adolescent and young adult population were developed as functions of subject covariates. These models may serve as the geometric basis to develop individualized head FE models for injury assessment and design of head-borne equipment. [ABSTRACT FROM AUTHOR]

Background: Post-traumatic stress disorder (PTSD) is commonly associated with alcohol and substance use disorders (ASUD). A randomized, placebo-controlled, phase 3 trial demonstrated the safety and efficacy of MDMA-assisted therapy (MDMA-AT) for the treatment of severe PTSD. This analysis explores patterns of alcohol and substance use in patients receiving MDMA-AT compared to placebo plus therapy (Placebo+Therapy).Methods: Adult participants with severe PTSD (n = 90) were randomized to three blinded trauma-focused therapy sessions with either MDMA-AT or Placebo+Therapy. Eligible participants met DSM-5 criteria for severe PTSD and could meet criteria for mild (current) or moderate (early remission) alcohol or cannabis use disorder; other SUDs were excluded. The current analyses examined outcomes on standardized measures of hazardous alcohol (i.e., Alcohol Use Disorder Identification Test; AUDIT) and drug (i.e., Drug Use Disorder Identification Test; DUDIT) use at baseline prior to randomization and at study termination.Results: There were no treatment group differences in AUDIT or DUDIT scores at baseline. Compared to Placebo+therapy, MDMA-AT was associated with a significantly greater reduction in mean (SD) AUDIT change scores (Δ = -1.02 (3.52) as compared to placebo (Δ = 0.40 (2.70), F (80, 1) = 4.20, p = 0.0436; Hedge's g= .45). Changes in DUDIT scores were not significantly different between treatment groups.Conclusions: MDMA-AT for severe PTSD may also lead to subclinical improvements in alcohol use. MDMA-AT does not appear to increase risk of illicit drug use. These data provide preliminary evidence to support the development of MDMA-AT as an integrated treatment for co-occurring PTSD and ASUD. [ABSTRACT FROM AUTHOR]

Carbon nanotubes (CNTs) are a novel nanocarriers with interesting physical and chemical properties. Here we investigate the ability of amino-functionalized multi-walled carbon nanotubes (MWNTs-NH 3 + ) to cross the Blood-Brain Barrier (BBB) in vitro using a co-culture BBB model comprising primary porcine brain endothelial cells (PBEC) and primary rat astrocytes, and in vivo following a systemic administration of radiolabelled f -MWNTs. Transmission Electron microscopy (TEM) confirmed that MWNTs-NH 3 + crossed the PBEC monolayer via energy-dependent transcytosis. MWNTs-NH 3 + were observed within endocytic vesicles and multi-vesicular bodies after 4 and 24 h. A complete crossing of the in vitro BBB model was observed after 48 h, which was further confirmed by the presence of MWNTs-NH 3 + within the astrocytes. MWNT-NH 3 + that crossed the PBEC layer was quantitatively assessed using radioactive tracers. A maximum transport of 13.0 ± 1.1% after 72 h was achieved using the co-culture model. f -MWNT exhibited significant brain uptake (1.1 ± 0.3% injected dose/g) at 5 min after intravenous injection in mice, after whole body perfusion with heparinized saline. Capillary depletion confirmed presence of f -MWNT in both brain capillaries and parenchyma fractions. These results could pave the way for use of CNTs as nanocarriers for delivery of drugs and biologics to the brain, after systemic administration. [ABSTRACT FROM AUTHOR]

Background: Many patients with chest pain do not receive follow-up from a physician after discharge from the emergency department despite significant survival benefit associated with follow-up care. Our objective was to evaluate factors associated with physician follow-up to understand this gap in practice. Methods: We conducted an observational study involving patients at high risk who were assessed for chest pain and discharged from an emergency department in Ontario between April 2004 and March 2010. We used multivariable logistic regression to determine the association of clinical and nonclinical characteristics with physician follow-up. Results: We identified 56 767 patients, of whom 25.1% did not receive any follow-up by a physician, 69.0% were seen by their primary care physician, and 17.3% were seen by a cardiologist within 30 days. Patients who had medical comorbidities and cardiac conditions such as myocardial infarction or heart failure were less likely to have follow-up. In contrast, a previous visit to a primary care physician was associated with the highest odds of having physician follow-up (odds ratio [OR] 6.44, 95% confidence interval [CI] 5.91-7.01). Similarly, a previous visit to a cardiologist was strongly associated with follow-up by a cardiologist (OR 3.01, 95% CI 2.85-3.17). Patients evaluated in emergency departments with the highest tertile of chest pain volume were more likely to receive follow-up from any physician (OR 1.52, 95% CI 1.31-1.77) and from a cardiologist (OR 2.04, 95% CI 1.61-2.57). Interpretation: Nonclinical factors are strongly associated with physician follow-up for patients with chest pain after discharge from the emergency department. However, patients with comorbidities and at higher risk for future adverse events are less likely to receive follow-up care. [ABSTRACT FROM AUTHOR]

Carbon nanotubes (CNTs) exhibit unique properties which have led to their applications in the biomedical field as novel delivery systems for diagnosis and therapy purposes. We have previously reported that the degree of functionalization of CNTs is a key factor determining their biological behaviour. The present study broadens the spectrum by investigating the impact of the diameter of CNTs using two series of multi-walled CNTs (MWNTs) with distinct differences in their diameters. Both MWNTs were doubly functionalized by 1,3-dipolar cycloaddition and amidation reactions, allowing the appended functional groups to be further conjugated with radionuclide chelating moieties and antibodies or antibody fragments. All constructs possessed comparable degree of functionalization and were characterized by thermogravimetric analysis, transmission electron microscopy, gel electrophoresis and surface plasmon resonance. The MWNT conjugates were radio-labelled with indium-111, which thereby enabled in vivo single photon emission computed tomography/computed tomography (SPECT/CT) imaging and organ biodistribution study using γ-scintigraphy. The narrow MWNTs (average diameter: 9.2 nm) demonstrated enhanced tissue affinity including non-reticular endothelial tissues compared to the wider MWNTs (average diameter: 39.5 nm). The results indicate that the higher aspect ratio of narrow MWNTs may be beneficial for their future biological applications due to higher tissue accumulation. [ABSTRACT FROM AUTHOR]

Background Studies show that anaphylaxis is under-recognized and epinephrine (adrenaline) is under-used by medical personnel as well as patients and their families. This study assesses the knowledge of food-induced anaphylaxis diagnosis and management across different populations of providers and caregivers and other interested respondents. Methods An online survey embedded in a case discussion of food-induced anaphylaxis was distributed by Medscape to registered members. Results A total of 7822 responders who started the activity chose to answer at least some of the questions presented (response rate 39.5%). Over 80% of responders in all groups correctly identified the case of anaphylaxis with prominent skin and respiratory symptoms; however, only 55% correctly recognized the case without skin symptoms as anaphylaxis. Only 23% of responders correctly selected risk factors for anaphylaxis, with physicians significantly more likely to choose the correct answers as compared to allied health, other health professionals, and medical students (p < 0.001). Ninety-five percent selected epinephrine (adrenaline) as the most appropriate treatment for anaphylaxis, and 81% correctly indicated that there are no absolute contraindications for epinephrine (adrenaline) in the setting of anaphylaxis. When presented a case of a child with no documented history of allergies who has symptoms of anaphylaxis, more physicians than any other group chose to administer stock epinephrine (adrenaline) (73% vs. 60%, p < 0.001). Conclusion Specific knowledge deficits for food-induced anaphylaxis persist across all groups. Further educational efforts should be aimed not only at the medical community but also for the entire caregiver community and general public, to optimize care for food allergic individuals. [ABSTRACT FROM AUTHOR]

Carbon nanotubes (CNTs) are one of the most promising nanomaterials to be used in biomedicine for drug/gene delivery as well as biomedical imaging. This study develops radio-labeled, iron oxide-decorated multiwalled CNTs (MWNTs) as dual magnetic resonance (MR) and single photon emission computed tomography (SPECT) contrast agents. Hybrids containing different amounts of iron oxide are synthesized by in situ generation. Physicochemical characterisations reveal the presence of superparamagnetic iron oxide nanoparticles (SPION) granted the magnetic properties of the hybrids. Further comprehensive examinations including high resolution transmission electron microscopy (HRTEM), fast Fourier transform simulations, X-ray diffraction, and X-ray photoelectron spectroscopy assure the conformation of prepared SPION as γ-Fe2O3. High r2 relaxivities are obtained in both phantom and in vivo MRI compared to the clinically approved SPION Endorem. The hybrids are successfully radio labeled with technetium-99m through a functionalized bisphosphonate and enable SPECT/CT imaging and γ-scintigraphy to quantitatively analyze the biodistribution in mice. No abnormality is found by histological examination and the presence of SPION and MWNT are identified by Perls stain and Neutral Red stain, respectively. TEM images of liver and spleen tissues show the co-localization of SPION and MWNTs within the same intracellular vesicles, indicating the in vivo stability of the hybrids after intravenous injection. The results demonstrate the capability of the present SPION-MWNT hybrids as dual MRI and SPECT contrast agents for in vivo use. [ABSTRACT FROM AUTHOR]

Objective Excess weight and physical inactivity are modifiable risk factors for breast cancer. Training women to use self-help resources over the internet has potential for reducing intervention costs and enhancing maintenance. Methods A total of 50 overweight/obese women at increased breast cancer risk were randomized to a 12-week intervention or a comparison group. Telephone-based sessions trained participants to use web-based self-monitoring tools to set goals and track diet and exercise. The comparison group received dietary information but no training. At baseline and 12 weeks, participants were weighed and wore an accelerometer. Results Participants were aged 60.9 ± 0.8 years with a BMI of 33.1 ± 0.6 kg/m2. The intervention group lost 3.3 ± 4.0 kg, whereas the comparison group gained 0.9 ± 3.4 kg ( p < 0.0001). Intervention participants who found the website helpful lost 5.6 ± 0.7 kg; those who did not lost 0.8 ± 0.9 kg ( p < 0.001). Change in physical activity was +70 ± 140 min/week among those who found the website helpful, −6 ± 75 min/week among those who did not, and −34 ± 207 min/week in the comparison group ( p < 0.01). Conclusions A program to train women to use web-based weight loss tools achieved a substantial short-term weight loss among the majority of participants. Further follow-up is needed to assess weight loss maintenance over time. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

A review of the article "Prevalence of Immunodeficiency in Children With Invasive Pneumococcal Disease in the Pneumococcal Vaccine Era: A Systematic Review," by C. Butters et al, which appeared in a 2019 issue of the journal "JAMA Pediatrics" is presented.