Trajectories of Opioid Misuse and Opioid Use Disorder Among Adults With Chronic Pain and HIV: An Observational Study.

OBJECTIVES: In a longitudinal cohort of patients with HIV and chronic pain, we sought to (1) identify trajectories of opioid misuse and opioid use disorder (OUD) symptoms, and to (2) determine whether prescription opioid dose was associated with symptom trajectories. METHODS: We leveraged an existing 12-month longitudinal observational study, Project PIMENTO, of persons living with HIV and chronic pain who received care at a hospital system in the Bronx, New York. A quota sampling strategy was used to ensure variability of prescribed opioid use in the recruited sample. Research interviews occurred quarterly and assessed opioid behaviors and criteria for OUD. To describe symptom trajectories, we conducted 2 separate longitudinal latent class analyses to group participants into (1) opioid misuse and (2) OUD trajectories. Finally, we used multinomial logistic regression models to examine the relationship between baseline prescription opioid dose and symptom trajectories. RESULTS: Of 148 total participants, at baseline 63 (42.6%) had an active opioid prescription, 69 (46.6%) met the criteria for current opioid misuse, and 44 (29.7%) met the criteria for current OUD. We found 3 opioid misuse and 3 OUD symptom trajectories, none of which showed worsened symptoms over time. In addition, we found that higher prescription opioid dose at baseline was associated with a greater OUD symptom trajectory. CONCLUSIONS: Opioid misuse and OUD were common but stable or decreasing over time. Although these results are reassuring, our findings also support prior studies that high-dose opioid therapy is associated with greater OUD symptoms.

Imaging spatiotemporal translation regulation in vivo.

Translation is regulated spatiotemporally to direct protein synthesis when and where it is needed. RNA localization and local translation have been observed in various subcellular compartments, allowing cells to rapidly and finely adjust their proteome post-transcriptionally. Local translation on membrane-bound organelles is important to efficiently synthesize proteins targeted to the organelles. Protein-RNA phase condensates restrict RNA spatially in membraneless organelles and play essential roles in translation regulation and RNA metabolism. In addition, the temporal translation kinetics not only determine the amount of protein produced, but also serve as an important checkpoint for the quality of ribosomes, mRNAs, and nascent proteins. Translation imaging provides a unique capability to study these fundamental processes in the native environment. Recent breakthroughs in imaging enabled real-time visualization of translation of single mRNAs, making it possible to determine the spatial distribution and key biochemical parameters of in vivo translation dynamics. Here we reviewed the recent advances in translation imaging methods and their applications to study spatiotemporal translation regulation in vivo.

Distribution and molecular evolution of the anti-CRISPR family AcrIF7.

Anti-clustered regularly interspaced short palindromic repeats (CRISPRs) are proteins capable of blocking CRISPR-Cas systems and typically their genes are located on mobile genetic elements. Since their discovery, numerous anti-CRISPR families have been identified. However, little is known about the distribution and sequence diversity of members within a family, nor how these traits influence the anti-CRISPR's function and evolution. Here, we use AcrIF7 to explore the dissemination and molecular evolution of an anti-CRISPR family. We uncovered 5 subclusters and prevalent anti-CRISPR variants within the group. Remarkably, AcrIF7 homologs display high similarity despite their broad geographical, ecological, and temporal distribution. Although mainly associated with Pseudomonas aeruginosa, AcrIF7 was identified in distinct genetic backgrounds indicating horizontal dissemination, primarily by phages. Using mutagenesis, we recreated variation observed in databases but also extended the sequence diversity of the group. Characterisation of the variants identified residues key for the anti-CRISPR function and other contributing to its mutational tolerance. Moreover, molecular docking revealed that variants with affected function lose key interactions with its CRISPR-Cas target. Analysis of publicly available data and the generated variants suggests that the dominant AcrIF7 variant corresponds to the minimal and optimal anti-CRISPR selected in the family. Our study provides a blueprint to investigate the molecular evolution of anti-CRISPR families.

Nanoemulsified Formulation of Cedrela odorata Essential Oil and Its Larvicidal Effect against Spodoptera frugiperda (J.E. Smith).

Cedrela odorata L. is a plant species from the Meliaceae family that is cultivated for timber production. Although the C. odorata essential oil (EO) contains mainly sesquiterpenes, its insecticidal potential is unknown. The lipophilic properties and high degradation capacity of EOs have limited their application for use in pest control. However, the currently available knowledge on the nanoemulsification of EOs, in addition to the possibility of improving their dispersion, would allow them to prolong their permanence in the field. The objective of the present work was to develop a nanoemulsion of the C. odorata EO and to evaluate its larvicidal activity against Spodoptera frugiperda. The EO was obtained by the hydrodistillation of C. odorata dehydrated leaves, and the nanoemulsion was prepared with non-ionic surfactants (Tween 80 and Span 80) using a combined method of agitation and dispersion with ultrasound. The stability of the nanoemulsion with a droplet diameter of <200 nm was verified in samples stored at 5 °C and 25 °C for 90 days. Both the C. odorata EO and its corresponding nanoemulsion presented lethal properties against S. frugiperda. The results obtained provide guidelines for the use of wood waste to produce sustainable and effective insecticides in the fight against S. frugiperda. In addition, considering that a phytochemical complex mixture allows the simultaneous activation of different action mechanisms, the development of resistance in insects is slower.

Efficient interlayer exciton transport in two-dimensional metal-halide perovskites.

Two-dimensional (2D) metal-halide perovskites are attractive for use in light harvesting and light emitting devices, presenting improved stability as compared to the more conventional three-dimensional perovskite phases. Significant attention has been paid to influencing the layer orientation of 2D perovskite phases, with the charge-carrier transport through the plane of the material being orders of magnitude more efficient than the interlayer transport. Importantly though, the thinnest members of the 2D perovskite family exhibit strong exciton binding energies, suggesting that interlayer energy transport mediated by dipole-dipole coupling may be relevant. We present transient microscopy measurements of the interlayer energy transport in the (PEA)2PbI4 perovskite. We find efficient interlayer exciton transport (0.06 cm2 s-1), which translates into a diffusion length that exceeds 100 nm and a sub-ps timescale for energy transfer. While still slower than the in-plane exciton transport (0.2 cm2 s-1), our results show that excitonic energy transport is considerably less anisotropic than charge-carrier transport for 2D perovskites.

A two-track model for the spatiotemporal coordination of bacterial septal cell wall synthesis revealed by single-molecule imaging of FtsW.

Synthesis of septal peptidoglycan (sPG) is crucial for bacterial cell division. FtsW, an indispensable component of the cell division machinery in all walled bacterial species, was recently identified in vitro as a peptidoglycan glycosyltransferase (PGTase). Despite its importance, the septal PGTase activity of FtsW has not been demonstrated in vivo. How its activity is spatiotemporally regulated in vivo has also remained elusive. Here, we confirmed FtsW as an essential septum-specific PGTase in vivo using an N-acetylmuramic acid analogue incorporation assay. Next, using single-molecule tracking coupled with genetic manipulations, we identified two populations of processively moving FtsW molecules: a fast-moving population correlated with the treadmilling dynamics of the essential cytoskeletal FtsZ protein and a slow-moving population dependent on active sPG synthesis. We further identified that FtsN, a potential sPG synthesis activator, plays an important role in promoting the slow-moving population. Our results suggest a two-track model, in which inactive sPG synthases follow the 'Z-track' to be distributed along the septum and FtsN promotes their release from the Z-track to become active in sPG synthesis on the slow 'sPG-track'. This model provides a mechanistic framework for the spatiotemporal coordination of sPG synthesis in bacterial cell division.

Vasorelaxant activity of Euphorbia furcillata Kunth mainly by activation of NO/cGMP pathway and calcium channel blockade / Actividad vasorrelajante de Euphorbia furcillata Kunth principalmente por activación de la vía NO/GMPc y bloqueo de canales de calcio]

The aim of current study was to determinate ex vivo and chromatographic fingerprint by HPLC of four extracts of Euphorbia furcillata K. Ethyl acetate extract of Euphorbia furcillata (EaEEf) was the most effective and potent extract (Emax=98.69±1.24%) and its effect was partially endothelium-dependent. Functional vasorelaxant mechanism of action of EaEEf was determinate, EaEEf showed efficient relaxation of KCl [80 mM]-induced contraction and norepinephrine and CaCl2 contraction curves showed diminution of maximal contraction in the presence of EAEEf and EaEEf-relaxation curve was shifted to the right in the presence of L-NAME (nitric oxide synthase inhibitor) and ODQ (guanylate cyclase inhibitor). Chromatographic fingerprints analysis suggests presence of diterpenoid such as abietane, tigliane, and ingenane skeletons. Our experiments suggest the EaEEf vasorelaxant activity could be attributed to diterpenoid molecules whose mechanism involves nitric oxide production and calcium channel blockade.

Se determinó el efecto vasorrelajante ex vivo y los perfiles cromatográficos mediante HPLC de cuatro extractos de Euphorbia furcillata K.. El extracto de acetato de etilo de E. furcillata (EaEEf) fue el más eficaz y potente en la contracción inducida por norepinefrina (Emax=98.69±1.24%) y el efecto fue parcialmente dependiente del endotelio vascular. Se determinó el mecanismo de acción vasorrelajante para EaEEf, este mostró ser eficaz sobre la contracción inducida por KCl [80 mM] y la curva de contracción en respuesta a norepinefrina y CaCl2 en presencia de EaEEf mostró disminución en la contracción máxima, mientras que la curva de relajación de EaEEf en presencia de L-NAME (inhibidor de óxido nítrico sintasa) y ODQ (inhibidor de guanilato ciclasa) se desplazó hacia la derecha. El análisis cromatográfico de EaEEf sugiere la presencia de moléculas diterpenoides como abietano, tigliano y esqueletos de ingenano. Nuestros resultados sugieren que el efecto vasorrelajante de EaEEf podría atribuirse a moléculas diterpenoides, cuyo mecanismo de acción involucra la producción de óxido nítrico y bloqueo de canales de calcio.

An Open-Label Pilot Study of Duloxetine in Patients With Irritable Bowel Syndrome and Comorbid Major Depressive Disorder.

Major depressive disorder (MDD) and irritable bowel syndrome (IBS) frequently co-occur, yet treating their comorbid presentation is challenging. Low-dose tricyclic antidepressants are efficacious for IBS, but higher doses to treat depressive symptoms present tolerability problems, whereas selective serotonin reuptake inhibitors are more tolerable but show inconsistent efficacy for IBS. If efficacious, serotonin-norepinephrine reuptake inhibitors like duloxetine would provide a useful alternative. We explored efficacy, tolerability, and time to onset of action of duloxetine in comorbid IBS-MDD in an open-label, 12-week trial. Repeated-measures mixed-effects regression analysis with the intent-to-treat sample assessed rate of change of the clinician-administered Gastrointestinal Symptoms Rating Scale, Montgomery-Åsberg Depression Rating Scale, and other clinician-administered and self-report scales. Seventeen Hispanic adults with current MDD and comorbid IBS meeting Rome III criteria entered the study. Medical and laboratory assessment ruled out alarm symptoms and signs inconsistent with IBS. Duloxetine led to significant improvement in Gastrointestinal Symptoms Rating Scale and Montgomery-Åsberg Depression Rating Scale scores and 71.4% and 64.3% intent-to-treat response rates for IBS and MDD, respectively. Abdominal pain severity decreased by 56%. Contrary to expectation of rapid analgesic effects, based on duloxetine studies for neuropathic pain, both IBS and MDD symptoms improved gradually; differences in slopes of improvement were nonsignificant. Duloxetine was moderately well tolerated at a mean endpoint dose of 60 mg/d. Study limitations include the lack of placebo control, modest sample size, single ethnic group, and high attrition rate. Duloxetine efficacy for comorbid IBS-MDD should be studied under placebo-controlled conditions with larger and more diverse samples.

Toward a cultural adaptation of pharmacotherapy: Latino views of depression and antidepressant therapy.

Relative to non-Latino Whites, Latinos in the United States with major depressive disorder (MDD) show low engagement in antidepressant therapy, whether engagement is defined as pharmacotherapy access, medication initiation, pill-taking, or treatment retention. One potential reason for this disparity in depression care is the low cultural congruence of pharmacotherapy for this population. To examine Latinos' views of depression and antidepressant therapy, we conducted qualitative interviews with 30 Latino outpatients initiating antidepressants prior to their first treatment visit using the semistructured Treatment Adherence and Retention Questionnaire. These baseline interviews were randomly selected from data collected for a randomized controlled trial testing a novel intervention to enhance engagement by depressed Latino outpatients. Participant narratives were analyzed using open coding and the iterative analytical approach derived from grounded theory. Patient views about depression addressed stigmatizing views held by others in their social circle. Most participants directly refuted these views by providing alternate explanations to depression experiences. Antidepressant therapy narratives also revealed marked stigmatization, but participants tended not to refute these views. Instead, patients expressed concerns about antidepressants and showed marked ambivalence about seeking psychiatric care. Participants, however, did suggest ways in which clinicians and patients might collaborate to address their concerns about antidepressants. Some cultural views, such as concerns about addiction to or dependence on medication, may be negotiable barriers to treatment. Prescribing clinicians should address cultural views and concerns in order to improve Latino engagement in antidepressant therapy.

Tree mineral nutrition is deteriorating in Europe.

The response of forest ecosystems to increased atmospheric CO2 is constrained by nutrient availability. It is thus crucial to account for nutrient limitation when studying the forest response to climate change. The objectives of this study were to describe the nutritional status of the main European tree species, to identify growth-limiting nutrients and to assess changes in tree nutrition during the past two decades. We analysed the foliar nutrition data collected during 1992-2009 on the intensive forest monitoring plots of the ICP Forests programme. Of the 22 significant temporal trends that were observed in foliar nutrient concentrations, 20 were decreasing and two were increasing. Some of these trends were alarming, among which the foliar P concentration in F. sylvatica, Q. Petraea and P. sylvestris that significantly deteriorated during 1992-2009. In Q. Petraea and P. sylvestris, the decrease in foliar P concentration was more pronounced on plots with low foliar P status, meaning that trees with latent P deficiency could become deficient in the near future. Increased tree productivity, possibly resulting from high N deposition and from the global increase in atmospheric CO2, has led to higher nutrient demand by trees. As the soil nutrient supply was not always sufficient to meet the demands of faster growing trees, this could partly explain the deterioration of tree mineral nutrition. The results suggest that when evaluating forest carbon storage capacity and when planning to reduce CO2 emissions by increasing use of wood biomass for bioenergy, it is crucial that nutrient limitations for forest growth are considered.

Fatalism or destiny? A qualitative study and interpretative framework on Dominican women's breast cancer beliefs.

BACKGROUND: A growing literature on Latino's beliefs about cancer focuses on the concept of fatalismo (fatalism), despite numerous conceptual ambiguities concerning its meaning, definition, and measurement. This study explored Latina women's views on breast cancer and screening within a cultural framework of destino ("destiny"), or the notion that both personal agency and external forces can influence health and life events. METHODS: Semi-structured interviews were conducted with 25 Latinas from the Dominican Republic aged 40 or over. RESULTS: Respondents reported complex notions of health locus of control that encompassed both internal (e.g., individual action) and external (e.g., the will of God) forces shaping breast cancer prevention efforts. Furthermore, women actively participated in screening because they believed that cancer could become a death sentence if diagnosed late or left untreated. DISCUSSION: In contrast to simplistic notions of "fatalism", our analysis suggests complex strategies and beliefs regarding breast cancer and cancer screening that speak of resiliency rather than hopelessness.

Divorcio destructivo: cuando uno de los padres aleja activamente al otro de la vida de sus hijos / Destructive divorce: When one of the parents moves away the other from their children's life

Las consideraciones contenidas en este artículo derivan del trabajo como mediadora en causas familiares en contextos judiciales, de la práctica clínica como terapeuta familiar y de pareja, y de una investigación cualitativa realizada en la Facultad de Psicología, en la que se entrevistó a 12 "padres alejados", indagando acerca de las consecuencias que produjo en ellos el ser apartados de sus hijos, y a 8 expertos (asesores de familia, abogados y psicólogos de los tribunales de familia). Se encontró que estar involucrados en este proceso provoca en los padres consecuencias físicas, psicológicas y sociales en diferentes grados. Así mismo, se estableció que las acciones ejercidas desde la justicia son poco eficaces para ayudar a desarticular las conductas de entorpecimiento de la vinculación del progenitor alienador, salvo en los casos leves, donde las indicaciones y el peso de la ley terminan respetándose, aunque de manera irregular.

The different considerations contained in this paper are derived from the job as a mediator in family conflicts in judicial contexts, from the clinical practice with families, parenting and marriage problems, and from a qualitative research made in the Psychology program, in which 12 "moved-away parents" were asked about the consequences produced in theirs-self being moved-away from their sons, and 8 experts (advisers of family, lawyers and psychologists of the courts of family). It was found that to be involve in this situations incite in the parents different degrees of physics, physiological and social consequences. In the same way, it was established that actions exerted from justice are ineffective to help to disarticulate the conducts of obstruction for the entailment of the disturber parent. Except in slight cases where the indications and the laws end up being respected, although of irregular way.

Commentary: fatalismo reconsidered: a cautionary note for health-related research and practice with Latino populations.

Over recent years, interest has grown in studying whether fatalismo (fatalism) deters Latinos from engaging in various health promotion and disease detection behaviors, especially with regard to cancer screening. This commentary presents problematic issues posed by the concept of fatalism, focusing on research on Latinos and cancer screening. We discuss key findings in the literature, analyze methodologic and conceptual problems, and highlight structural contexts and other barriers to health care as critical to the fatalism concept. Although the need to better understand the role of fatalistic beliefs on health is great, we discuss the public health implications of reaching premature conclusions concerning the effect of fatalism on Latinos' cancer screening behaviors.

Tuberculosis y afectividad / Tuberculosis and affectivity

Se investigaron las percepciones, actitudes, prejuicios y comportamientos asociados a la tuberculosis y diferencias debidas al género, porque esta presenta un fuerte estigma social con matices culturales según la sociedad. La conducta más reportada resultó tratar de ocultarla. Se realizaron entrevistas grupales y una encuesta a 147 enfermos de La Habana. Se comprobó la persistencia del estigma y las conductas asociadas fueron: seguimiento del tratamiento lejos del lugar de residencia, ocultamiento activo y el motivo predominante declarado, en mayor proporción por las mujeres fue evitar el rechazo social. No se encontraron afectaciones a la búsqueda de atención médica ni al seguimiento del tratamiento. Apreciaciones asociadas a la enfermedad fueron sentir vergüenza por padecerla, que se les trata con temor, que para hacer una vida normal hay que ocultarla y más de la tercera parte lo aconsejaría. Se recomendó diseñar una estrategia de comunicación social.

It was proposed to investigate the perceptions, attitudes, prejudices and behaviors associated with tuberculosis, as well as the differences due to gender because it presents a strong social stigma with cultural shades according to society. The most reported behavior is trying to hide it. Group interviews were made and a survey was done to 147 patients in Havana. The persistance of the stigma was proved and the associated conducts were follow-up of the treatment far away from the residence place and active hiding (occultation). The main reason declared mostly among women was to avoid social rejection. No affectations were found neither in the search of medical attention nor in the follow-up of treatment. Appreciations associated with the disease were feeling shame for suffering from tuberculosis, be treated with fear, that to lead a normal life they have to hide the disease, and that more than the third part of them would advise to do so. It was recommended to design a strategy of social communication.

[Risk factors for Giardia lamblia infection in children in daycare centers in Havana, Cuba]. / Factores de riesgo de la infección por Giardia lamblia en niños de guarderías infantiles de Ciudad de la Habana, Cuba.

We conducted a longitudinal study on giardiasis in three daycare centers in Havana City for a period of 18 months and described a group of children with a "predisposition" or tendency towards re-infection with Giardia lamblia. This group was found to be more frequently associated with clinical symptoms such as diarrhea. A case-control study was designed to determine whether socioeconomic factors and hygiene were associated with this phenomenon. We found no differences between the groups with regard to overcrowding rates, number of persons per bed, absence of certain electric appliances, mother's schooling, or mean family income. However, there were proportionally more fathers with less than complete secondary education among cases as compared to controls. In addition, we found no differences in lack of hand-washing before eating and after defecation; however, we found a higher percentage of families who washed vegetables insufficiently among predisposed children. Finally, a lower percentage of families with predisposed children boiled their water. Our results demonstrate the important role of water as a vehicle for transmission of giardiasis and the importance of various epidemiologic factors.

Factores de riesgo de la infección por Giardia lamblia en niños de guarderías infantiles de Ciudad de La Habana, Cuba / Risk factors for Giardia lamblia in children in daycare centers in Havana, Cuba

En un estudio longitudinal sobre giardiasis desarrollado durante 18 meses en tres guarderías infantiles de Ciudad de La Habana, describimos un grupo de niños con tendencia o "predisposición" a la infección por Giardia lamblia; a los que se les encontró con síntomas clínicos más asociados a las diarreas. Este estudio de casos y controles se desarrolló para conocer si algunos factores socioeconómicos y hábitos higiénicos estaban asociados con este fenómeno. No se encontraron diferencias entre ambos grupos en las tasas de hacinamiento, el índice de personas por cama, en la carencia de determinados equipos eléctricos, en el nivel escolar de las madres, y en el promedio del ingreso familiar; sin embargo, predominó una frecuencia mayor de padres con nivel escolar menor de 12 grado en los casos que en los controles. No se encontraron diferencias entre ambos grupos en cuanto a la ausencia de lavado de manos antes de comer y después de defecar, pero se encontró un mayor porcentaje de lavado incorrecto de vegetales, y una menor frecuencia del hábito de hervir el agua de consumo en las familias de los casos. Estos resultados demuestran el papel del agua como vehículo de transmisión en la giardiasis y la importancia de algunos factores epidemiológicos

Conocimientos de la población sobre el cólera

Con el objetivo de determinar el impacto de la campaña educativa sobre el cólera en los conocimientos y creencias de la población, se realizó en 1993 una encuesta a 1 324 personas de 14 provincias y el municipio especial Isla de la Juventud. El 85 % tenía entre 20 y 59 años y el nivel escolar del 89 % era de secundaria básica o superior. El 69 % tenía los conocimientos mínimos para enfrentar la enfermedad, el 90 % acudiría al médico si la sospechara, el 72 % conocía que la diarrea es el síntoma principal del cólera, el 54 % sabía cómo se transmite, el 89 % creía que se puede contagiar por medio del agua de beber, el 54 % entendía la importancia de suministrarle líquidos al enfermo y el 78 % comprendía la importancia de lavarse las manos antes de comer y cocinar. Se concluye que, si bien la población tiene conocimientos generales sobre la enfermedad, por encontrarse nuestro país en una zona endémica debe reforzarse la educación para la salud, específicamente en los aspectos relacionados con la transmisión y con el incremento de la ingestión de líquidos a los enfermos.

In order to determine the impact of the educational campaing about cholera on the knowledge and believes of the population, a survey was made in 1993 among 1 324 poersons from 14 provinces and from Isla de la Juventud special municipality. 85 % were 20-59 years oldand 89 % had an secondary basic or higher educational level. 69 % had the minimun knowledge to face the disease, 90 % would see a doctor if they had and suspicion, 72 % knew that diarrhea is the main symptom of cholera, 54 % new how it is transmitted 89 % thought that they may be infected by drinking water, 54 % understood the importance of giving liquids to the sick subject, and 78 % realized the significance of washing their hands before eating anf cooking. It is concluded that even though our population has a general knowledge about the disease, due to the fact that our country is located in an endemic zone, health education must be reinforced, specifically those aspects connected with the communication and with the increase of liquids administration to the patients.