Aplicación de tecnologías móviles (m-Salud) y salud electrónica (e-Salud) en el manejo y en la prevención de la litiasis renal: revisión sistemática / Mobile and eHealth technologies in the management and prevention of nephrolithiasis: A systematic review

Introducción La litiasis renal (LR) es una enfermedad urológica común, que a menudo requiere de cuidados a largo plazo. Las tecnologías de salud móvil (m-Salud) y salud electrónica (e-Salud) tienen el potencial de mejorar el manejo de las enfermedades crónicas e impactar sobre los patrones de la conducta. Para evaluar la aplicabilidad de estas herramientas en la mejora del tratamiento y la prevención de la LR, nos propusimos evaluar los datos actuales sobre el uso, los beneficios y las limitaciones de la m-Salud y la e-Salud en la LR. Métodos Se realizó una revisión sistemática de los estudios de investigación primaria sobre m-Salud y e-Salud en la evaluación y tratamiento de la LR. Dos investigadores independientes examinaron las citas por título y resumen para determinar su pertinencia y, a continuación, se realizó una revisión del texto completo para obtener un resumen descriptivo de los estudios. Resultados Se incluyeron 37 artículos para el análisis. Las principales áreas de interés fueron: 1) botellas de agua «inteligentes» y aplicaciones de dispositivos móviles para el seguimiento del consumo de líquidos, que mostraron un aumento de la ingesta en la mayoría de los estudios; 2) plataformas de seguimiento de stent ureterales, que mejoraron la tasa de stent retenidos a largo plazo; 3) clínicas virtuales para el tratamiento de la LR, las cuales han mejorado el acceso, han reducido costes y han mostrado resultados satisfactorios; 4) plataformas de endoscopia para teléfonos inteligentes, que ofrecieron una buena calidad de imagen respecto a sus costes en entornos de recursos limitados, y 5) información sobre la LR en línea para pacientes, la cual generalmente se caracterizó por ser de mala calidad y/o precisión, particularmente en YouTube®. La mayoría de los estudios eran pruebas de concepto o estudios de intervención de un solo brazo, con una evaluación limitada de la eficacia o de los resultados clínicos a largo plazo. Conclusiones ... (AU)

Introduction Kidney stone disease (KSD) is a common urological condition that often requires long-term care. Mobile health (mHealth) and eHealth technologies have the potential to enhance chronic disease management and behavioral change. To assess opportunities to apply these tools to improve KSD treatment and prevention, we aimed to assess current evidence on the use, benefits, and limitations of mHealth and eHealth in KSD. Methods We performed a systematic review of primary research studies of mHealth and eHealth in the evaluation and management of KSD. Two independent researchers screened citations by title and abstract for relevance, then full-text review was performed for descriptive summary of the studies. Results A total of 37 articles were included for analysis. Primary domains of evidence included: 1) “smart” water bottles and mobile-device apps for tracking fluid consumption, which showed increased intake in most studies; 2) ureteral stent tracking platforms, which improved the rate of long-term retained stents; 3) virtual stone clinics, which have been suggested to increase access, lower costs, and have satisfactory outcomes; 4) smartphone-based endoscopy platforms, which offered cost-effective image quality in resource-limited settings; 5) patient information about KSD online, which was typically characterized as poor quality and/or accuracy, particularly on YouTube. Most studies were proof-of-concept or single-arm intervention designs, with limited assessment of effectiveness or long-term clinical outcomes. Conclusions Mobile and eHealth technologies have significant real-world applications to KSD prevention, intervention, and patient education. A lack of rigorous effectiveness studies currently limits evidence-based conclusions and incorporation in clinical guidelines. (AU)

Mobile and eHealth technologies in the management and prevention of nephrolithiasis: A systematic review.

INTRODUCTION: Kidney stone disease (KSD) is a common urological condition that often requires long-term care. Mobile health (mHealth) and eHealth technologies have the potential to enhance chronic disease management and behavioral change. To assess opportunities to apply these tools to improve KSD treatment and prevention, we aimed to assess current evidence on the use, benefits, and limitations of mHealth and eHealth in KSD. METHODS: We performed a systematic review of primary research studies of mHealth and eHealth in the evaluation and management of KSD. Two independent researchers screened citations by title and abstract for relevance, then full-text review was performed for descriptive summary of the studies. RESULTS: A total of 37 articles were included for analysis. Primary domains of evidence included: 1) "smart" water bottles and mobile-device apps for tracking fluid consumption, which showed increased intake in most studies; 2) ureteral stent tracking platforms, which improved the rate of long-term retained stents; 3) virtual stone clinics, which have been suggested to increase access, lower costs, and have satisfactory outcomes; 4) smartphone-based endoscopy platforms, which offered cost-effective image quality in resource-limited settings; 5) patient information about KSD online, which was typically characterized as poor quality and/or accuracy, particularly on YouTube. Most studies were proof-of-concept or single-arm intervention designs, with limited assessment of effectiveness or long-term clinical outcomes. CONCLUSIONS: Mobile and eHealth technologies have significant real-world applications to KSD prevention, intervention, and patient education. A lack of rigorous effectiveness studies currently limits evidence-based conclusions and incorporation in clinical guidelines.

Late Toxicity and Long-Term Local Control in Patients With Ultra-Central Lung Tumours Treated by Intensity-Modulated Radiotherapy-Based Stereotactic Ablative Body Radiotherapy With Homogenous Dose Prescription.

AIMS: To report late toxicity and long-term outcomes of intensity-modulated radiotherapy (IMRT)-based stereotactic ablative body radiotherapy (SABR) in patients with ultra-central lung tumours. MATERIALS AND METHODS: This is a single-institution retrospective analysis of patients treated with SABR for ultra-central tumours between May 2008 and April 2016. Ultra-central location was defined as tumour (GTV) abutting or involving trachea, main or lobar bronchi. Respiratory motion management and static-field dynamic-IMRT were used, with dose prescribed homogeneously (maximum <120%). Descriptive analysis, Kaplan-Meier method, log-rank test and Cox regression were used to assess outcomes. RESULTS: Sixty-five per cent of patients had inoperable primary non-small cell lung cancer and 35% had lung oligometastases. The median age was 72 (range 34-85) years. The median gross tumour volume and planning target volume (PTV) were 19.6 (range 1.7-203.3) cm3 and 57.4 (range 7.7-426.6) cm3, respectively. The most commonly used dose fractionation was 60 Gy in eight fractions (n = 51, 87.8%). Median BED10 for D98%PTV and D2%PTV were 102.6 Gy and 115.06 Gy, respectively. With a median follow-up of 26.5 (range 3.2-100.5) months, fatal haemoptysis occurred in five patients (8.7%), of which two were directly attributable to SABR. A statistically significant difference was identified between median BED3 for 4 cm3 of airway, for patients who developed haemoptysis versus those who did not (147.4 versus 47.2 Gy, P = 0.005). At the last known follow-up, 50 patients (87.7%) were without local recurrence. Freedom from local progression at 2 and 4 years was 92 and 79.8%, respectively. The median overall survival was 34.3 (95% confidence interval 6.1-61.6) months. Overall survival at 2 and 4 years was 55.1 and 41.2%, respectively. CONCLUSION: In patients with high-risk ultra-central lung tumours, IMRT-based SABR with homogenous dose prescription achieves high local control, similar to that reported for peripheral tumours. Although fatal haemoptysis occurred in 8.7% of patients, a direct causality with SABR was evident in only 3%. Larger studies are warranted to ascertain factors associated with outcomes, especially toxicity, and identify patients who would probably benefit from this treatment.

Pilot Randomized Controlled Trial of Omega-3 and Individual-Family Psychoeducational Psychotherapy for Children and Adolescents With Depression.

The goal of this study is to evaluate feasibility and estimate effect sizes of omega-3 fatty acids (Ω3), individual-family psychoeducational psychotherapy (PEP), their combination, and moderating effects of maternal depression and psychosocial stressors in youth with depression. In a pilot 2 × 2 randomized controlled trial, 72 youth (ages 7-14; 57% Caucasian, 57% male) with major depression, dysthymia, or depression not otherwise specified were randomized to 12 weeks of Ω3, PEP+placebo, Ω3+PEP, or placebo. Ω3 versus placebo was double-masked. Evaluators masked to condition assessed depressive severity at baseline (randomization) and at 2, 4, 6, 9, and 12 weeks using the Children's Depression Rating Scale-Revised. Side effects were either absent or mild. PEP was administered with 74% fidelity. Remission was 77%, Ω3+PEP; 61%, PEP+placebo; 44%, Ω3; 56%, placebo. Intent-to-treat analyses found small to medium effects of combined treatment (d = .29) and Ω3 monotherapy (d = .42), but negligible effect for PEP+placebo (d < .10), all compared to placebo alone. Relative to placebo, youth with fewer social stressors responded better to Ω3 (p = .04), PEP (p = .028), and their combination (p = .035), and those with maternal depression responded better to PEP (p = .020) than did those without maternal depression. Remission rates were favorable compared to other studies of psychotherapy and comparable to an existing randomized controlled trial of Ω3; results warrant further evaluation in a larger sample. Ω3 was well tolerated. Active treatments show significantly more placebo-controlled depression improvement in the context of maternal depression and fewer stressors, suggesting that they may benefit depression with a more endogenous than environmental origin.

Predicting enrollment in two randomized controlled trials of nonpharmacologic interventions for youth with primary mood disorders.

BACKGROUND: As recruitment and retention are often challenging in randomized controlled trials (RCTs), this study sought to identify predictors of participation (i.e., trial enrollment). METHOD: These analyses identified predictors of enrollment among 119 youth, ages 7-14, with a primary mood disorder, who screened eligible for the Omega-3 and Therapy pilot studies; 95 (79.8%) actually participated in the treatment. RESULTS: Youth who received some form of travel assistance (16.0%) almost uniformly enrolled in the treatment portion of the RCT. Youth who lived further away from the study site (p = .047) or whose primary caregiver never married (p = .01) were less likely to enroll. Of note, socioeconomic status (SES) variables (parent education and child insurance status) did not significantly predict enrollment, suggesting that study incentives or accommodations may have adequately addressed barriers commonly associated with SES. LIMITATIONS: Due to the fairly high trial enrollment rate (approximately 80%), there likely was limited power to detect some differences between groups. Generalizability may be limited to youth with a primary mood disorder diagnosis. CONCLUSIONS: Despite retaining a large proportion of the youth who screened eligible, participant self-selection is a limitation of any RCT. A silent inclusion criterion of any RCT is willingness to be randomized.

Mechanisms Through Which Supportive Relationships with Parents and Peers Mitigate Victimization, Depression and Internalizing Problems in Children Bullied by Peers.

This study investigated how supportive relationships with peers and parents protect children against ongoing victimization, internalizing problems and depression. The longitudinal data set tracked progress of 111 children recruited for the trial of Resilience Triple P, and previously bullied by peers. Informants included children, parents and teachers. Higher levels of facilitative parenting (warm parenting that supports peer relationships) and peer acceptance predicted lower later levels of both depression and victimization over time. Higher levels of child friendedness predicted lower levels of child reports of internalizing problems. Children's friendships, acceptance by same sex peers and facilitative parenting all played moderating roles in protecting against ongoing victimization and internalizing problems. Peer acceptance mediated the relationships between facilitative parenting and victimization. Facilitative parenting mediated the relationship between peer acceptance and depression. It was concluded that supportive relationships with parents and peers play important and complementary roles in protecting children against ongoing victimization and depression.

Susceptibility of Culex quinquefasciatus (Diptera: Culicidae) in Southern Louisiana to Larval Insecticides.

Mosquito control districts conduct rigorous insecticide treatments against both larval and adult Culex quinquefasciatus Say (Diptera: Culicidae), the primary vector of West Nile virus in the southern United States. However, the development of resistant populations of Cx. quinquefasciatus in response to extensive larvicide or adulticide applications has been demonstrated repeatedly across the world. Examining changes in insecticide susceptibility in treated field areas can help inform mosquito control districts as to whether or not their treatments remain effective. We hypothesized that frequent insecticide applications for the control of mosquitoes in East Baton Rouge Parish, Louisiana, lowered susceptibility of wild Cx. quinquefasciatus to larvicides. Larvicide susceptibility was measured using Lysinibacillus sphaericus, spinosad, and temephos in populations of Cx. quinquefasciatus sampled from sites in three Parishes where frequencies of insecticide applications varied, and frequencies of resistance were measured relative to a susceptible reference colony. Susceptibility to these larvicides was widespread, although fourfold resistance to the organophosphate temephos was detected at one site in East Baton Rouge Parish in the spring of 2016, which increased to eightfold resistance by the end of the mosquito season. Activities of esterases were found to be elevated in wild, temephos-resistant mosquitoes, indicating the potential role of these enzymes as a mechanism of resistance. The results of this study provide a baseline of comparison for future measurements of susceptibility in Cx. quinquefasciatus in Louisiana, and may help inform local mosquito control districts as to the effectiveness and sustainability of their insecticide programs.

Testing of an oral dosing technique for double-crested cormorants, Phalacocorax auritus, laughing gulls, Leucophaeus atricilla, homing pigeons, Columba livia, and western sandpipers, Calidris mauri, with artificially weather MC252 oil.

Scoping studies were designed to determine if double-crested cormorants (Phalacocorax auritus), laughing gulls (Leucophaues atricilla), homing pigeons (Columba livia) and western sandpipers (Calidris mauri) that were gavaged with a mixture of artificially weathered MC252 oil and food for either a single day or 4-5 consecutive days showed signs of oil toxicity. Where volume allowed, samples were collected for hematology, plasma protein electrophoresis, clinical chemistry and electrolytes, oxidative stress and organ weigh changes. Double-crested cormorants, laughing gulls and western sandpipers all excreted oil within 30min of dose, while pigeons regurgitated within less than one hour of dosing. There were species differences in the effectiveness of the dosing technique, with double-crested cormorants having the greatest number of responsive endpoints at the completion of the trial. Statistically significant changes in packed cell volume, white cell counts, alkaline phosphatase, alanine aminotransferase, creatine phosphokinase, gamma glutamyl transferase, uric acid, chloride, sodium, potassium, calcium, total glutathione, glutathione disulfide, reduced glutathione, spleen and liver weights were measured in double-crested cormorants. Homing pigeons had statistically significant changes in creatine phosphokinase, total glutathione, glutathione disulfide, reduced glutathione and Trolox equivalents. Laughing gulls exhibited statistically significant decreases in spleen and kidney weight, and no changes were observed in any measurement endpoints tested in western sandpipers.

Toxic effects of orally ingested oil from the Deepwater Horizon spill on laughing gulls.

The explosion of the Deepwater Horizon oil rig released, millions of gallons of oil into the environment, subsequently exposing wildlife, including numerous bird species. To determine the effects of MC252 oil to species relevant to the Gulf of Mexico, studies were done examining multiple exposure scenarios and doses. In this study, laughing gulls (Leucophaeus atricilla, LAGU) were offered fish injected with MC252 oil at target doses of 5 or 10mL/kg bw per day. Dosing continued for 27 days. Of the adult, mixed-sex LAGUs used in the present study, ten of 20 oil exposed LAGUs survived to the end of the study; a total of 10 of the oil exposed LAGUs died or were euthanized within 20 days of initiation of the study. Endpoints associated with oxidative stress, hepatic total glutathione (tGSH), oxidized glutathione (GSSG) and reduced glutathione (rGSH) significantly increased as mean dose of oil increased, while the rGSH:GSSG ratio showed a non-significant negative trend with oil dose. A significant increase in 3-methyl histidine was found in oil exposed birds when compared to controls indicative of muscle wastage and may have been associated with the gross observation of diminished structural integrity in cardiac tissue. Consistent with previous oil dosing studies in birds, significant changes in liver, spleen, and kidney weight when normalized to body weight were observed. These studies indicate that mortality in response to oil dosing is relatively common and the mortality exhibited by the gulls is consistent with previous studies examining oil toxicity. Whether survival effects in the gull study were associated with weight loss, physiologic effects of oil toxicity, or a behavioral response that led the birds to reject the dosed fish is unknown.

Dermal exposure to weathered MC252 crude oil results in echocardiographically identifiable systolic myocardial dysfunction in double-crested cormorants (Phalacrocorax auritus).

During the Deepwater Horizon Natural Resource Damage Assessment, gross morphologic cardiac abnormalities, including softer, more distensible musculature, were noted upon gross necropsy in hearts from laughing gulls and double-crested cormorants exposed to weathered MC252 crude oil. A species specific, echocardiographic technique was developed for antemortem evaluation of function that was used to evaluate and better characterize cardiac dysfunction. Control (n=12) and treated (n=13) cormorant groups of similar sex-ratio and ages were dermally treated with approximately 13ml of water or weathered MC252 crude oil, respectively, every 3 days for 6 dosages. This resulted in a low to moderate external exposure. Upon visualization and clinical assessment of the hearts of all test subjects, comprehensive diagnostic cardiographic measurements were taken twice, prior to oil application and after a 21day dermal oil exposure. Oil-treated birds showed a decrease in cardiac systolic function, as characterized by an increased left ventricular internal dimension-systole and left ventricular stroke volume as well as concurrent decreased left ventricular ejection fraction and left ventricular fractional shortening when compared to both control birds' and the treated birds' time zero values. These changes are indicative of a possible dilative cardiomyopathy induced by oil exposure, although further elucidation of possible collagen damage is recommended. Arrhythmias including tachycardia in two treated birds and bradycardia in all treated birds were documented, indicating further clinically significant abnormalities induced by MC252 oil that warrant further investigation. A statistically significant increase in free calcium concentration, important to muscular and neurologic function in treated birds was also noted. This study documents that weathered MC252 oil caused clinically significant cardiac dysfunction that could result in mortality and decrease recruitment.

Reprint of: Overview of avian toxicity studies for the Deepwater Horizon Natural Resource Damage Assessment.

The Oil Pollution Act of 1990 establishes liability for injuries to natural resources because of the release or threat of release of oil. Assessment of injury to natural resources resulting from an oil spill and development and implementation of a plan for the restoration, rehabilitation, replacement or acquisition of natural resources to compensate for those injuries is accomplished through the Natural Resource Damage Assessment (NRDA) process. The NRDA process began within a week of the Deepwater Horizon oil spill, which occurred on April 20, 2010. During the spill, more than 8500 dead and impaired birds representing at least 93 avian species were collected. In addition, there were more than 3500 birds observed to be visibly oiled. While information in the literature at the time helped to identify some of the effects of oil on birds, it was not sufficient to fully characterize the nature and extent of the injuries to the thousands of live oiled birds, or to quantify those injuries in terms of effects on bird viability. As a result, the US Fish and Wildlife Service proposed various assessment activities to inform NRDA injury determination and quantification analyses associated with the Deepwater Horizon oil spill, including avian toxicity studies. The goal of these studies was to evaluate the effects of oral exposure to 1-20ml of artificially weathered Mississippi Canyon 252 oil kg bw-1 day-1 from one to 28 days or one to five applications of oil to 20% of the bird's surface area. It was thought that these exposure levels would not result in immediate or short-term mortality but might result in physiological effects that ultimately could affect avian survival, reproduction and health. These studies included oral dosing studies, an external dosing study, metabolic and flight performance studies and field-based flight studies. Results of these studies indicated changes in hematologic endpoints including formation of Heinz bodies and changes in cell counts. There were also effects on multiple organ systems, cardiac function and oxidative status. External oiling affected flight patterns and time spent during flight tasks indicating that migration may be affected by short-term repeated exposure to oil. Feather damage also resulted in increased heat loss and energetic demands. The papers in this special issue indicate that the combined effects of oil toxicity and feather effects in avian species, even in the case of relatively light oiling, can significantly affect the overall health of birds.

Overview of avian toxicity studies for the Deepwater Horizon Natural Resource Damage Assessment.

The Oil Pollution Act of 1990 establishes liability for injuries to natural resources because of the release or threat of release of oil. Assessment of injury to natural resources resulting from an oil spill and development and implementation of a plan for the restoration, rehabilitation, replacement or acquisition of natural resources to compensate for those injuries is accomplished through the Natural Resource Damage Assessment (NRDA) process. The NRDA process began within a week of the Deepwater Horizon oil spill, which occurred on April 20, 2010. During the spill, more than 8500 dead and impaired birds representing at least 93 avian species were collected. In addition, there were more than 3500 birds observed to be visibly oiled. While information in the literature at the time helped to identify some of the effects of oil on birds, it was not sufficient to fully characterize the nature and extent of the injuries to the thousands of live oiled birds, or to quantify those injuries in terms of effects on bird viability. As a result, the US Fish and Wildlife Service proposed various assessment activities to inform NRDA injury determination and quantification analyses associated with the Deepwater Horizon oil spill, including avian toxicity studies. The goal of these studies was to evaluate the effects of oral exposure to 1-20ml of artificially weathered Mississippi Canyon 252 oil kg bw-1 day-1 from one to 28 days or one to five applications of oil to 20% of the bird's surface area. It was thought that these exposure levels would not result in immediate or short-term mortality but might result in physiological effects that ultimately could affect avian survival, reproduction and health. These studies included oral dosing studies, an external dosing study, metabolic and flight performance studies and field-based flight studies. Results of these studies indicated changes in hematologic endpoints including formation of Heinz bodies and changes in cell counts. There were also effects on multiple organ systems, cardiac function and oxidative status. External oiling affected flight patterns and time spent during flight tasks indicating that migration may be affected by short-term repeated exposure to oil. Feather damage also resulted in increased heat loss and energetic demands. The papers in this special issue indicate that the combined effects of oil toxicity and feather effects in avian species, even in the case of relatively light oiling, can significantly affect the overall health of birds.

Limited impacts of truck-based ultra-low-volume applications of mosquito adulticides on mortality in honey bees (Apis mellifera).

Adulticides applied against mosquitoes can reduce vector populations during times of high arbovirus transmission. However, impacts of these insecticides on pollinators and other non-target organisms are of concern to mosquito control professionals, beekeepers and others. We evaluated mortality of Culex quinquefasciatus and Apis mellifera when caged insects were exposed to low and high label rates of four common adulticides (Aqua-Pursuit™ [permethrin], Duet® [prallethrin + sumithrin], Fyfanon® [malathion] and Scourge® [resmethrin]) at six distances up to 91.4 m from a truck-mounted ultra-low-volume sprayer. Honey bee mortality was both absolutely low (61 m had limited impacts on honey bee mortality while providing effective mosquito control.

Antecedents of Treatment Resistant Depression in Children Victimized by Peers.

Children victimized by peers are at increased risk of ongoing depression. This study investigates treatment resistant depression in children victimized by peers, following participation in a targeted cognitive behavioral family intervention. The sample comprised 39 children aged 6-12 years with elevated depression compared with a general sample, prior to the intervention. Six months after the intervention, 26 were no longer depressed and 13 were still depressed. This study investigated the differentiation of these two groups on the basis of parenting and child factors. Children with treatment resistant depression were discriminated from other children by lower levels of peer support and facilitative parenting immediately after the intervention. It was concluded that ongoing support from parents and peers is needed to reduce the risk of ongoing depression even if victimization has been reduced. Further research could develop a comprehensive profile of children at risk of depression following peer victimization.

A Randomized Controlled Trial of Individual Family Psychoeducational Psychotherapy and Omega-3 Fatty Acids in Youth with Subsyndromal Bipolar Disorder.

OBJECTIVE: This pilot study evaluates efficacy of omega-3 fatty acid supplementation (Ω3), individual family psychoeducational psychotherapy (IF-PEP), and their combination in youth with subsyndromal bipolar disorders (bipolar disorder not otherwise specified [BP-NOS], cyclothymic disorder [CYC]). METHODS: This study was a 12 week, randomized trial of Ω3 versus placebo and IF-PEP versus active monitoring (AM) using a 2 × 2 design (Ω3 + PEP: n = 5; Ω3 + AM: n = 5; placebo + PEP: n = 7; placebo + AM: n = 6). Twenty-three youth ages 7-14 with BP-NOS or CYC were recruited via community advertisements and clinician referrals. Participants could be taking stable medication for attention-deficit/hyperactivity disorder and sleep aids, but no other psychotropics. Independent evaluators assessed participants at screen, baseline, and 2, 4, 6, 9, and 12 weeks. Primary outcome measures were the Kiddie Schedule for Affective Disorders (K-SADS) Depression (KDRS) and Mania (KMRS) Rating Scales, Children's Depression Rating Scale-Revised (CDRS-R), and Young Mania Rating Scale (YMRS). Ω3/placebo conditions were double-blind; independent evaluators were blind to psychotherapy condition. RESULTS: Most participants (83%) completed the 12 week trial. Side effects were uncommon and mild. Intent-to-treat analyses indicated significant improvement in depressive symptoms (KDRS) for combined treatment relative to placebo and AM (p = 0.01, d = 1.70). Across groups, manic symptoms improved over time without significant treatment effects. Effect of IF-PEP on child depression compared with AM was medium (d = 0.63, CDRS-R) to large (d = 1.24, KDRS). Effect of Ω3 on depression was medium (d = 0.48, KDRS). CONCLUSION: IF-PEP and Ω3 are well tolerated and associated with improved mood symptoms among youth with BP-NOS and CYC. Clinicaltrials.gov Identifier: NCT01507753.

Modulus-dependent macrophage adhesion and behavior.

Macrophage attachment and activation to implanted materials is crucial in determining the extent of acute and chronic inflammation, and biomaterials degradation. In an effort to improve implant performance, considerable attention has centered on altering material surface chemistry to modulate macrophage behavior. In this work, the influence of the modulus of a material on the behavior of model macrophages (i.e., human promonocytic THP-1 cells) was investigated. We synthesized interpenetrating polymer network (IPN) coatings with varying moduli to test the hypothesis that lower moduli surfaces attenuate THP-1 cell attachment and activation. The surface chemistry and moduli of the IPN coatings were characterized using X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM), respectively. THP-1 cells preferentially attached to stiffer coatings of identical surface chemistry, confirming that fewer macrophages attach to lower moduli surfaces. The secretion of human TNF-alpha, IL-10, IL-8 and IL-1beta from THP-1 cells attached to the IPNs was measured to assess the concentration of both pro- and anti-inflammatory cytokines. The global amount of TNF-alpha released did not vary for IPN surfaces of different moduli; however, the amount of the pro-inflammatory cytokine IL-8 released demonstrated a biphasic response, where lower (approx. 1.4 kPa) and very high (approx. 348 kPa) moduli IPN surfaces attenuated IL-8 secretion. The different trends for TNF-alpha and IL-8 secretion highlight the complexity of the wound healing response, suggesting that there may not be a unique surface chemistry and substratum modulus combination that minimizes the pro-inflammatory cytokines produced by activated macrophages.

Modifying the surface charge of single track-etched conical nanopores in polyimide.

Chemical modification of nanopore surfaces is of great interest as it means that the surface composition is no longer fixed by the choice of substrate material, even to the point where large biomolecules can be attached to the pore walls. Controlling nanopore transport characteristics is one important application of surface modification which is very relevant given the significant interest in sensors based on the transport of ions and molecules through nanopores. Reported here is a method to change the surface charge polarity of single track-etched conical nanopores in polyimide, which also has the potential to attach more complex molecules to the carboxyl groups on the nanopore walls. These carboxyl groups were converted into terminal amino groups, first by activation with N-(3-dimethylaminopropyl)-N-ethylcarbodiimide (EDC) and N-hydroxysuccinimide (NHS) followed by the covalent coupling of ethylenediamine. This results in a changed surface charge polarity. Regeneration of a carboxyl-terminated surface was also possible, by reaction of the amino groups with succinic anhydride. The success of these reactions was confirmed by measurements of the pore's pH sensitive current-voltage (I-V) characteristics before and after the chemical modification, which depend on surface charge. The permselectivity of the pores also changed accordingly with the modification.