Carbon Nanotube–Liposome Complexes in Hydrogels for Controlled Drug Delivery via Near-Infrared Laser Stimulation

Externally controllable drug delivery systems are crucial for a variety of biological applications where the dosage and timing of drug delivery need to be adjusted based on disease diagnosis and progression. Here, we have developed an externally controllable drug delivery system by combining three extensively used platforms: hydrogels, liposomes, and single-walled carbon nanotubes (SWCNTs). We have developed carbon nanotube–liposome complexes (CLCs) and incorporated these structures into a 3D alginate hydrogel for use as an optically controlled drug delivery system. The CLC structures were characterized by using a variety of imaging and spectroscopic techniques, and an optimal SWCNT/lipid ratio was selected. The optimal CLCs were loaded with a model drug (FITC-Dex), incorporated into a hydrogel, and their release profile was studied. It was shown that release of the drug cargo can be triggered by using an NIR laser stimulation tuned to the optical resonance of a particular SWCNT species. It was further shown that the amount of released cargo can be tuned by varying the NIR stimulation time. This system demonstrates the externally controlled delivery of drug cargo and can be used for different applications including cancer chemotherapy delivery

Effect of Opioid vs Nonopioid Medications on Pain-Related Function in Patients With Chronic Back Pain or Hip or Knee Osteoarthritis Pain

Importance: Limited evidence is available regarding long-term outcomes of opioids compared with nonopioid medications for chronic pain. Objective: To compare opioid vs nonopioid medications over 12 months on pain-related function, pain intensity, and adverse effects. Design, Setting, and Participants: Pragmatic, 12-month, randomized trial with masked outcome assessment. Patients were recruited from Veterans Affairs primary care clinics from June 2013 through December 2015; follow-up was completed December 2016. Eligible patients had moderate to severe chronic back pain or hip or knee osteoarthritis pain despite analgesic use. Of 265 patients enrolled, 25 withdrew prior to randomization and 240 were randomized. Interventions: Both interventions (opioid and nonopioid medication therapy) followed a treat-to-target strategy aiming for improved pain and function. Each intervention had its own prescribing strategy that included multiple medication options in 3 steps. In the opioid group, the first step was immediate-release morphine, oxycodone, or hydrocodone/acetaminophen. For the nonopioid group, the first step was acetaminophen (paracetamol) or a nonsteroidal anti-inflammatory drug. Medications were changed, added, or adjusted within the assigned treatment group according to individual patient response. Main Outcomes and Measures: The primary outcome was pain-related function (Brief Pain Inventory [BPI] interference scale) over 12 months and the main secondary outcome was pain intensity (BPI severity scale). For both BPI scales (range, 0-10; higher scores = worse function or pain intensity), a 1-point improvement was clinically important. The primary adverse outcome was medication-related symptoms (patient-reported checklist; range, 0-19). Results: Among 240 randomized patients (mean age, 58.3 years; women, 32 [13.0%]), 234 (97.5%) completed the trial. Groups did not significantly differ on pain-related function over 12 months (overall P = .58); mean 12-month BPI interference was 3.4 for the opioid group and 3.3 for the nonopioid group (difference, 0.1 [95% CI, -0.5 to 0.7]). Pain intensity was significantly better in the nonopioid group over 12 months (overall P = .03); mean 12-month BPI severity was 4.0 for the opioid group and 3.5 for the nonopioid group (difference, 0.5 [95% CI, 0.0 to 1.0]). Adverse medication-related symptoms were significantly more common in the opioid group over 12 months (overall P = .03); mean medication-related symptoms at 12 months were 1.8 in the opioid group and 0.9 in the nonopioid group (difference, 0.9 [95% CI, 0.3 to 1.5]). Conclusions and Relevance: Treatment with opioids was not superior to treatment with nonopioid medications for improving pain-related function over 12 months. Results do not support initiation of opioid therapy for moderate to severe chronic back pain or hip or knee osteoarthritis pain

Communicating with providers about racial healthcare disparities: The role of providers’ prior beliefs on their receptivity to different narrative frames

Objective Evaluate narratives aimed at motivating providers with different pre-existing beliefs to address racial healthcare disparities. Methods Survey experiment with 280 providers. Providers were classified as high or low in attributing disparities to providers (HPA versus LPA) and were randomly assigned to a non-narrative control or 1 of 2 narratives: “Provider Success” (provider successfully resolved problem involving Black patient) and “Provider Bias” (Black patient experienced racial bias, which remained unresolved). Participants' reactions to narratives (including identification with narrative) and likelihood of participating in disparities-reduction activities were immediately assessed. Four weeks later, participation in those activities was assessed, including self-reported participation in a disparities-reduction training course (primary outcome). Results Participation in training was higher among providers randomized to the Provider Success narrative compared to Provider Bias or Control. LPA participants had higher identification with Provider Success than Provider Bias narratives, whereas among HPA participants, differences in identification between the narratives were not significant. Conclusions Provider Success narratives led to greater participation in training than Provider Bias narratives, although providers’ pre-existing beliefs influenced the narrative they identified with. Practice implications Provider Success narratives may be more effective at motivating providers to address disparities than Provider Bias narratives, though more research is needed

Epigenetic influences may explain dental differences in monozygotic twin pairs

The document attached has been archived with permission from the Australian Dental Association (8th Jan 2008). An external link to the publisher’s copy is included.Background: Comparisons between monozygotic (MZ) co-twins have tended to focus on the similarities between their dentitions rather than differences. The aim of this study was to determine the prevalence of discordant expression for simple hypodontia and supernumerary teeth in MZ twin pairs and to explain how phenotypic differences might occur despite their similar genotypes. Methods: Records of 278 pairs of MZ twins, including dental casts and radiographs, were examined and the prevalences of discordant expression for missing upper lateral incisors (ULI) or second premolars (PM2), and of mesiodentes, were determined. Zygosities were confirmed by comparisons of blood markers and DNA. Results: There was evidence of at least one missing ULI or PM2 in 24 of the 278 MZ pairs (8.6 per cent), with 21 of these 24 pairs (87.5 per cent) showing discordant expression. Nine of the 278 MZ pairs (3.2 per cent) displayed evidence of mesiodentes, with eight of these nine pairs (88.9 per cent) being discordant. Conclusion: Our findings show that differences in the expression of missing or extra teeth occur often between MZ co-twins whose genetic make-up predisposes them to simple hypodontia or mesiodentes. We postulate that minor variations in epigenetic events during odontogenesis may account for these distinct differences.GC Townsend, L Richards, T Hughes, S Pinkerton and W Schwerd

Developmental disturbances associated with agenesis of the permanent maxillary lateral incisor

The aim of this study was to characterise the intra and extra-oral phenotype associated with agenesis of the permanent maxillary lateral incisor. We compared three groups: (1) subjects with agenesis of one or both permanent maxillary lateral incisors (n=80); (2) first and second degree relatives of group 1 with no agenesis of the permanent maxillary lateral incisor and (3) subjects with no agenesis of the maxillary lateral incisor or family history of it (n=49). For each of the 201 subjects detailed clinical information was reviewed and panoramic radiographs were analysed. Considering only the sample with unilateral agenesis, microdontia of the contralateral permanent maxillary lateral incisor was significantly more frequent in group 1 (82.4%) than in group 2 (25%) and the control group (2%). This supports the theory that microdontia is a variable expression of the same developmental disturbance that causes tooth agenesis. The absence of third molars occurred more often in group 1 (36.2%) than in groups 2 and 3 (18.6% and 18.9% respectively), confirming that agenesis of third molars was markedly associated with the agenesis of the permanent maxillary lateral incisor. Agenesis of teeth other than third molars was not significantly different among subjects with agenesis of the permanent maxillary lateral incisor and their relatives. The frequencies of supernumerary teeth, permanent maxillary canine impaction, general health condition and minor anomalies were not significantly different between the three groups

Using visual methods to understand physical activity maintenance following cardiac rehabilitation

© 2015 Hardcastle et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Few studies have explored the factors associated with long-term maintenance of exercise following cardiac rehabilitation. The present study used auto-photography and interviews to explore the factors that influence motivation and continued participation in physical activity among post cardiac rehabilitation patients. Twenty-three semi-structured interviews were conducted alongside participant-selected photographs or drawings with participants that had continued participation in physical activity for at least two years following the cardiac rehabilitation programme. Participants were recruited from circuit training classes in East Sussex in the UK. Thematic content analysis revealed seven main themes: fear of death and ill health avoidance, critical incidents, overcoming aging, social influences, being able to enjoy life, provision of routine and structure, enjoyment and psychological well-being. Fear of death, illness avoidance, overcoming aging, and being able to enjoy life were powerful motives for continued participation in exercise. The social nature of the exercise class was also identified as a key facilitator of continued participation. Group-based exercise suited those that continued exercise participation post cardiac rehabilitation and fostered adherence

Involvement in surface antigen expression by a moonlighting FG-repeat nucleoporin in trypanosomes

Components of the nuclear periphery coordinate a multitude of activities, including macromolecular transport, cell-cycle progression, and chromatin organization. Nuclear pore complexes (NPCs) mediate nucleocytoplasmic transport, mRNA processing, and transcriptional regulation, and NPC components can define regions of high transcriptional activity in some organisms at the nuclear periphery and nucleoplasm. Lineage-specific features underpin several core nuclear functions and in trypanosomatids, which branched very early from other eukaryotes, unique protein components constitute the lamina, kinetochores, and parts of the NPCs. Here we describe a phenylalanine-glycine (FG)-repeat nucleoporin, TbNup53b, that has dual localizations within the nucleoplasm and NPC. In addition to association with nucleoporins, TbNup53b interacts with a known trans-splicing component, TSR1, and has a role in controlling expression of surface proteins including the nucleolar periphery-located, procyclin genes. Significantly, while several nucleoporins are implicated in intranuclear transcriptional regulation in metazoa, TbNup53b appears orthologous to components of the yeast/human Nup49/Nup58 complex, for which no transcriptional functions are known. These data suggest that FG-Nups are frequently co-opted to transcriptional functions during evolution and extend the presence of FG-repeat nucleoporin control of gene expression to trypanosomes, suggesting that this is a widespread and ancient eukaryotic feature, as well as underscoring once more flexibility within nucleoporin function