Transcranial Magnetic Stimulation to Treat Neuropathic Pain: A Bibliometric Analysis.

Neuropathic pain is caused by a lesion or disease of the somatosensory system and is one of the most incapacitating pain types, representing a significant non-met medical need. Due to the increase in research in the field and since innovative therapeutic strategies are required, namely in intractable neuropathic pain, neurostimulation has been used. Within this approach, transcranial magnetic stimulation (TMS) that uses a transient magnetic field to produce electrical currents over the cortex emerges as a popular method in the literature. Since this is an area in expansion and due to the putative role of TMS, we performed a bibliometric analysis in Scopus with the primary objective of identifying the scientific production related to the use of TMS to manage neuropathic pain. The research had no restrictions, and the analysis focused on the characteristics of the literature retrieved, scientific collaboration and main research topics from inception to 6 July 2023. A total of 474 articles were collected. A biggest co-occurrence between the terms "neuropathic pain" and "transcranial magnetic stimulation" was obtained. The journal "Clinical Neurophysiology" leads the Top 5 most productive sources. The United States is the most productive country, with 50% of US documents being "review articles", followed by France, with 56% of French documents being "original articles". Lefaucheur, JP and Saitoh, Y are the two most influential authors. The most frequent type of document was "original article". Most of the studies (34%) that identified the neuropathic pain type focused on traumatic neuropathic pain, although a large proportion (38%) did not report the neuropathic pain type. This study allows us to provide a general overview of the field of TMS application for neuropathic pain and is useful for establishing future directions of research in this field.

Temporary increase in circulating replication-competent latent HIV-infected resting CD4+ T cells after switch to an integrase inhibitor based antiretroviral regimen.

BACKGROUND: The principal barrier to an HIV cure is the presence of the latent viral reservoir (LVR), which has been understudied in African populations. From 2018 to 2019, Uganda instituted a nationwide rollout of ART consisting of Dolutegravir (DTG) with two NRTI, which replaced the previous regimen of one NNRTI and the same two NRTI. METHODS: Changes in the inducible replication-competent LVR (RC-LVR) of ART-suppressed Ugandans with HIV (n = 88) from 2015 to 2020 were examined using the quantitative viral outgrowth assay. Outgrowth viruses were examined for viral evolution. Changes in the RC-LVR were analyzed using three versions of a Bayesian model that estimated the decay rate over time as a single, linear rate (model A), or allowing for a change at time of DTG initiation (model B&C). FINDINGS: Model A estimated the slope of RC-LVR change as a non-significant positive increase, which was due to a temporary spike in the RC-LVR that occurred 0-12 months post-DTG initiation (p < 0.005). This was confirmed with models B and C; for instance, model B estimated a significant decay pre-DTG initiation with a half-life of 6.9 years, and an ∼1.7-fold increase in the size of the RC-LVR post-DTG initiation. There was no evidence of viral failure or consistent evolution in the cohort. INTERPRETATION: These data suggest that the change from NNRTI- to DTG-based ART is associated with a significant temporary increase in the circulating RC-LVR. FUNDING: Supported by the NIH (grant 1-UM1AI164565); Gilead HIV Cure Grants Program (90072171); Canadian Institutes of Health Research (PJT-155990); and Ontario Genomics-Canadian Statistical Sciences Institute.

Borrelia nietonii sp. nov.: Relapsing Fever Spirochetes Transmitted By the Tick Ornithodoros hermsi Designated Previously as Borrelia hermsii Genomic Group II.

Background: The taxonomic status of the relapsing fever spirochete Borrelia hermsii in western North America was established in 1942 and based solely on its specific association with the soft tick vector Ornithodoros hermsi. Multilocus sequence typing (MLST) of the 16S rRNA, flaB, gyrB, glpQ, and 16S-23S rRNA intergenic spacer of B. hermsii isolates collected over many years from various geographic locations and biological sources identified two distinct clades designated previously as B. hermsii Genomic Group I (GGI) and Genomic Group II (GGII). To better assess the taxonomic relationship of these two genomic groups to each other and other species of Borrelia, DNA sequences of the entire linear chromosome were determined. Materials and Methods: Genomic DNA samples were prepared from 11 spirochete isolates grown in Barbour-Stoenner-Kelly-H medium. From these preparations, DNA sequences of the entire linear chromosome of two isolates of B. hermsii belonging to each genomic group and seven additional species were determined. Results: Chromosomal sequences of four isolates of B. hermsii contained 919,212 to 922,307 base pairs. DNA sequence identities between the two genomic groups of B. hermsii were 95.86-95.99%, which were more divergent than chromosomal sequences comparing Borrelia parkeri and Borrelia turicatae (97.13%), Borrelia recurrentis and Borrelia duttonii (97.07%), and Borrelia crocidurae and B. duttonii (97.09%). The 3' end of the chromosome of the two GGII isolates also contained a unique intact oppA gene absent from all other species examined. Conclusion: Previous MLST and the chromosomal sequences presented herein support the division of the B. hermsii species complex into two species, B. hermsii sensu stricto ( = GGI) and Borrelia nietonii sp. nov. ( = GGII). We name this unique relapsing fever spirochete in honor of our late friend and colleague Dr. Nathan Nieto for his outstanding contributions to our understanding of tick-borne relapsing fever.

Three Decades of Research on the Development of Ibogaine Treatment of Substance Use Disorders: A Scientometric Analysis.

Ibogaine is a natural psychoactive drug that has been investigated for its potential role in the treatment of substance use disorders since the mid-1960s. To evaluate the interest in ibogaine's use as a therapeutic agent, we performed a scientometric analysis covering the last three decades (1993-2002, 2003-2012, and 2013-2022). A complementary analysis was performed to select and describe published clinical trials and meta-analyses. A total of 1523 references were found. Linear growth of publications in the first and third decades were identified, and the average number of publications from 1993 to 2002 was lower than that in the other two decades. Researchers from five continents were identified. Globally, academic research centers in the United States and Canada were the most productive. Cocaine, tobacco, morphine, and alcohol prevailed as major keywords in the first two decades and opioids and psychedelics were included in the third decade. A few key authors were the most co-referenced. One preclinical meta-analysis and no meta-analysis in humans were found. Research trends for ibogaine are widespread, growing, and consonant with current attentiveness in drug abuse. Our findings support the pressing need for rigorous clinical research on ibogaine to evaluate its efficacy and safety.

De novo assembly of Roseomonas mucosa isolated from patients with atopic dermatitis.

Roseomonas mucosa is associated with the normal skin microflora. Here, we present de novo sequence assemblies from R. mucosa isolates obtained from the skin lesions of three atopic dermatitis patients.

De novo assembly of Roseomonas mucosa isolates from healthy human volunteers used to treat atopic dermatitis.

Roseomonas mucosa is a bacterium that is found in the natural microbiota of human skin. Here, we present de novo sequence assemblies from R. mucosa isolated from the skin microflora of three healthy human volunteers that were used to treat atopic dermatitis patients.

Dating reservoir formation in virologically suppressed people living with HIV-1 in Rakai, Uganda.

The timing of the establishment of the HIV latent viral reservoir (LVR) is of particular interest, as there is evidence that proviruses are preferentially archived at the time of antiretroviral therapy (ART) initiation. Quantitative viral outgrowth assays (QVOAs) were performed using Peripheral Blood Mononuclear Cells (PBMC) collected from Ugandans living with HIV who were virally suppressed on ART for >1 year, had known seroconversion windows, and at least two archived ART-naïve plasma samples. QVOA outgrowth populations and pre-ART plasma samples were deep sequenced for the pol and gp41 genes. The bayroot program was used to estimate the date that each outgrowth virus was incorporated into the reservoir. Bayroot was also applied to previously published data from a South African cohort. In the Ugandan cohort (n = 11), 87.9 per cent pre-ART and 56.3 per cent viral outgrowth sequences were unique. Integration dates were estimated to be relatively evenly distributed throughout viremia in 9/11 participants. In contrast, sequences from the South African cohort (n = 9) were more commonly estimated to have entered the LVR close to ART initiation, as previously reported. Timing of LVR establishment is variable between populations and potentially viral subtypes, which could limit the effectiveness of interventions that target the LVR only at ART initiation.

Genetically diverse mouse models of SARS-CoV-2 infection reproduce clinical variation in type I interferon and cytokine responses in COVID-19.

Inflammation in response to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection drives severity of coronavirus disease 2019 (COVID-19) and is influenced by host genetics. To understand mechanisms of inflammation, animal models that reflect genetic diversity and clinical outcomes observed in humans are needed. We report a mouse panel comprising the genetically diverse Collaborative Cross (CC) founder strains crossed to human ACE2 transgenic mice (K18-hACE2) that confers susceptibility to SARS-CoV-2. Infection of CC x K18-hACE2 resulted in a spectrum of survival, viral replication kinetics, and immune profiles. Importantly, in contrast to the K18-hACE2 model, early type I interferon (IFN-I) and regulated proinflammatory responses were required for control of SARS-CoV-2 replication in PWK x K18-hACE2 mice that were highly resistant to disease. Thus, virus dynamics and inflammation observed in COVID-19 can be modeled in diverse mouse strains that provide a genetically tractable platform for understanding anti-coronavirus immunity.

Temporary increase in circulating replication-competent latent HIV-infected resting CD4+ T cells after switch to an integrase inhibitor based antiretroviral regimen.

The principal barrier to an HIV cure is the presence of a latent viral reservoir (LVR) made up primarily of latently infected resting CD4+ (rCD4) T-cells. Studies in the United States have shown that the LVR decays slowly (half-life=3.8 years), but this rate in African populations has been understudied. This study examined longitudinal changes in the inducible replication competent LVR (RC-LVR) of ART-suppressed Ugandans living with HIV (n=88) from 2015-2020 using the quantitative viral outgrowth assay, which measures infectious units per million (IUPM) rCD4 T-cells. In addition, outgrowth viruses were examined with site-directed next-generation sequencing to assess for possible ongoing viral evolution. During the study period (2018-19), Uganda instituted a nationwide rollout of first-line ART consisting of Dolutegravir (DTG) with two NRTI, which replaced the previous regimen that consisted of one NNRTI and the same two NRTI. Changes in the RC-LVR were analyzed using two versions of a novel Bayesian model that estimated the decay rate over time on ART as a single, linear rate (model A) or allowing for an inflection at time of DTG initiation (model B). Model A estimated the population-level slope of RC-LVR change as a non-significant positive increase. This positive slope was due to a temporary increase in the RC-LVR that occurred 0-12 months post-DTG initiation (p<0.0001). This was confirmed with model B, which estimated a significant decay pre-DTG initiation with a half-life of 7.7 years, but a significant positive slope post-DTG initiation leading to a transient estimated doubling-time of 8.1 years. There was no evidence of viral failure in the cohort, or consistent evolution in the outgrowth sequences associated with DTG initiation. These data suggest that either the initiation of DTG, or cessation of NNRTI use, is associated with a significant temporary increase in the circulating RC-LVR.

Perceptions of medical students towards the role of histology and embryology during curricular review.

BACKGROUND: The continuous changes in the medical education to prepare medical doctors for the future requires updates in medical curriculum. However, the perspectives of the medical students are not frequently considered during the revision of the medical curriculum. In parallel with the process of defining and adjusting the medical curriculum, a large survey was performed to inquire the perspectives of the medical students at the Faculty of Medicine of the University of Porto (FMUP), Portugal, about the role of Histology and of Embryology. METHODS: Medical students at FMUP (Portugal) completed a structured and anonymous online questionnaire about the subjects Histology and Embryology. The questionnaire was prepared using questions of previous surveys performed in Europe, including another Portuguese medical school, and additional questions that were specifically prepared to this study. The questions referred to teaching methods, clinical relevance, use of virtual (digital) microscopes and association of Histology and Embryology with other subjects of the medical curriculum. RESULTS: Four hundred and sixty-two students participated in the study. The students in clinical years were more likely to recognise the clinical relevance of Histology (p = 0.016) and Embryology (p < 0.001). Students agree that teaching of these subjects would benefit from a clinical orientation (89% for Histology; 90% for Embryology). Students highlighted that Histology is crucial to understand Biopathology and agree (75%) that an integration of Histology with Biopathology could be considered in the medical curriculum. Most students (55%) agree that slide microscopes are more useful than virtual microscopes. CONCLUSIONS: Our study contributes to the debate about the evolution of medical curriculum. Gathering the medical students' perceptions using large surveys such as that performed in the present study may be useful to adapt the methods of teaching which may increase the motivation of the students. In the case of Histology and Embryology at the FMUP (Portugal) providing more clinically oriented teaching may be useful to motivate the students. Students of clinical years have strong clinical perspectives of Histology and Embryology and their enrolment in teaching of Histology and Embryology can also contribute to increase motivation of younger students. Consulting and involving medical students in the development of the medical curriculum can be positive and students should be more responsible and engaged in building their own education.

Genetically diverse mouse models of SARS-CoV-2 infection reproduce clinical variation in type I interferon and cytokine responses in COVID-19.

Inflammation in response to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection drives severity of coronavirus disease 2019 (COVID-19) and is influenced by host genetics. To understand mechanisms of inflammation, animal models that reflect genetic diversity and clinical outcomes observed in humans are needed. We report a mouse panel comprising the genetically diverse Collaborative Cross (CC) founder strains crossed to human ACE2 transgenic mice (K18-hACE2) that confers susceptibility to SARS-CoV-2. Infection of CC x K18- hACE2 resulted in a spectrum of survival, viral replication kinetics, and immune profiles. Importantly, in contrast to the K18-hACE2 model, early type I interferon (IFN-I) and regulated proinflammatory responses were required for control of SARS-CoV-2 replication in PWK x K18-hACE2 mice that were highly resistant to disease. Thus, virus dynamics and inflammation observed in COVID-19 can be modeled in diverse mouse strains that provide a genetically tractable platform for understanding anti-coronavirus immunity.

Characterization of Innovation to Fight Child Mortality: A Systematic Scoping Review.

Objectives: This study aims to summarize how child mortality-a Sustainable Development Goal stated by the United Nations-has been explicitly addressed in the context of innovations. Methods: A scoping review following the PRISMA-ScR Statement was performed analysing indexed and non-indexed literature. Results: Empirical and non-disruptive innovation in the context of process targeting under-five mortality rate was the main subset of literature included in this article. The increment of literature on innovation in the context of SDGs over the last years denotes its growing importance and even though innovation aiming to reduce child mortality is currently being done, a significant part of it is not published in indexed databases but as grey literature. Conclusion: Empirical, disruptive innovation under a structural approach and empirical, non-disruptive innovation under a project point of view are the main types of innovation addressed in the literature and would be of utmost potential to reduce child mortality rate. A systematic review of the methods used for the measures of evaluation of applied innovations, their quality and results would be of great importance in the future.

Ecological relevance of non-perennial rivers for the conservation of terrestrial and aquatic communities.

River conservation efforts traditionally focus on perennial watercourses (i.e., those that do not dry) and their associated aquatic biodiversity. However, most of the global river network is not perennial and thus supports both aquatic and terrestrial biodiversity. We assessed the conservation value of nonperennial rivers and streams (NPRS) in one of Europe's driest regions based on aquatic (macroinvertebrates, diatoms) and terrestrial (riparian plants, birds, and carabid beetles) community data. We mapped the distribution of taxa at 90 locations and across wide environmental gradients. Using the systematic planning tool Marxan, we identified priority conservation sites under 2 scenarios: aquatic taxa alone or aquatic and terrestrial taxa together. We explored how environmental factors (runoff, flow intermittence, elevation, salinity, anthropogenic impact) influenced Marxan's site selection frequency. The NPRS were selected more frequently (over 13% on average) than perennial rivers when both aquatic and terrestrial taxa were considered, suggesting that NPRS have a high conservation value at the catchment scale. We detected an underrepresentation of terrestrial taxa (8.4-10.6% terrestrial vs. 0.5-1.1% aquatic taxa were unrepresented in most Marxan solutions) when priority sites were identified based exclusively on aquatic biodiversity, which points to a low surrogacy value of aquatic taxa for terrestrial taxa. Runoff explained site selection when focusing on aquatic taxa (all best-fitting models included runoff, r2  = 0.26-0.27), whereas elevation, salinity, and flow intermittence were more important when considering both groups. In both cases, site selection frequency declined as anthropogenic impact increased. Our results highlight the need to integrate terrestrial and aquatic communities when identifying priority areas for conservation in catchments with NPRS. This is key to overcoming drawbacks of traditional assessments based only on aquatic taxa and to ensure the conservation of NPRS, especially as NPRS become more prevalent worldwide due to climate change and increasing water demands.

Los esfuerzos de conservación fluvial se enfocan tradicionalmente en los cauces permanentes (aquellos que no se secan) y la biodiversidad acuática asociada. Sin embargo, la mayor parte de la red hidrográfica mundial no es permanente, por lo que sustenta biodiversidad tanto acuática como terrestre. Evaluamos el valor de conservación de los ríos y arroyos no permanentes (RANP) en una de las regiones más secas de Europa con datos de comunidades acuáticas (macroinvertebrados, diatomeas) y terrestres (escarabajos carábidos). Mapeamos la distribución de los taxones en 90 localidades que cubren gradientes ambientales amplios. Con la herramienta de planificación sistemática Marxan identificamos los sitios prioritarios de conservación bajo dos escenarios: considerando sólo los taxones acuáticos o los taxones acuáticos y terrestres juntos. Exploramos cómo los factores ambientales (escorrentía, intermitencia del caudal, altitud, salinidad, impacto antropogénico) influyeron sobre la frecuencia de selección de sitio de Marxan. Los RANP fueron seleccionados con mayor frecuencia (más del 13% en promedio) que los ríos permanentes cuando consideramos los taxones acuáticos y terrestres, lo que sugiere que los RANP tienen un valor elevado de conservación a escala de cuenca. Detectamos que los taxones terrestres estaban infrarrepresentados (8.4-10.6% taxones terrestres vs. 0.5-1.1% acuáticos no tuvieron representación en la mayoría de las soluciones de Marxan) cuando los sitios prioritarios para la conservación se identificaban exclusivamente con la biodiversidad acuática, lo que indica que los taxones acuáticos tienen un reducido valor indicador para los taxones terrestres. La escorrentía determinó la selección de sitios cuando se basó en los taxones acuáticos (los mejores modelos incluyeron la escorrentía, r2 = 0.26-0.27), mientras que la altitud, la salinidad y la intermitencia del caudal fueron más importantes cuando se consideraron ambos grupos. En ambos casos, la frecuencia de selección disminuyó conforme se incrementó el impacto antropogénico. Nuestros resultados resaltan la necesidad de integrar las comunidades terrestres y acuáticas a la identificación de las áreas prioritarias para la conservación de la biodiversidad en cuencas con RANP. Lo anterior es importante para superar las evaluaciones tradicionales basadas solamente en los taxones acuáticos y para garantizar la conservación de los RANP, especialmente ahora que estos son cada vez más frecuentes a nivel mundial debido al cambio climático y a la creciente demanda de agua.

Incidencia de litiasis vesicular asintomática en pacientes con complicaciones biliares / Incidence of asymptomatic gallstones in patients with biliary complications / Incidência de cálculos biliares asintomáticos em pacientes com complicações biliares

Introducción: Las complicaciones de la litiasis biliar (LB) son una causa importante de morbilidad en nuestro país y en el mundo entero y generan elevados costos en salud. Objetivo: El objetivo de este trabajo fue determinar, que pacientes con una complicación de su patología litiásica de la vía biliar (colecistitis, colangitis aguda, pancreatitis aguda), fueron previamente asintomáticos, resultando dicha complicación el debut de la enfermedad. Lugar: Sanatorio Asociación Española de Socorros Mutuos, Montevideo Uruguay. Diseño: Estudio observacional descriptivo, retrospectivo, análisis de historias clínicas. Materiales y Métodos: Se analizaron 234 casos clínicos. Se constató en este grupo de pacientes, características epidemiológicas, metodología diagnóstica, tratamientos recibidos y complicaciones. Resultados: Del total de pacientes (n=234), 109 (46.6%) tenían una litiasis vesicular asintomática (LVA) y la complicación biliar, fue el debut de su enfermedad. La colecistitis aguda fue la complicación más frecuente (68%), en segundo lugar, la colangitis aguda (22%) y en tercer lugar la pancreatitis aguda (10%). La edad promedio de presentación de la enfermedad fue los 59 años. Conclusiones: Casi la mitad de los pacientes (46.6%) que presentaron una complicación de su litiasis biliar eran asintomáticos. Este sería un argumento importante para indicar la colecistectomía laparoscópica con un criterio profiláctico en pacientes con una LVA.

Introduction : Complications of gallstones are an important cause of morbidity in our country and throughout the world and generate high health costs. Objective: The objective of this study was to determine which patients with a complication of their bile duct stone pathology (cholecystitis, acute cholangitis, acute pancreatitis) were previously asymptomatic, and this complication resulted in the onset of the disease. Place: Sanatorium Asociación Española de Socorros Mutuos, Montevideo Uruguay. Design: Descriptive and retrospective observational study with an analysis of medical records. Materials and Methods: 234 clinical cases were analyzed. Epidemiological characteristics, diagnostic methodology, treatments received, and complications were assessed in this group of patients. Results: Of the total number of patients (n=234), 109 (46.6%) had an asymptomatic gallbladder lithiasis and the biliary complication was the debut of their disease. Acute cholecystitis was the most frequent complication (68%), followed by acute cholangitis (22%) and third by acute pancreatitis (10%). The average age of presentation of the disease was 59 years. Conclusions: Almost half of the patients (46.6%) who presented a complication of their gallstones were asymptomatic. This would be an important argument to indicate laparoscopic cholecystectomy with a prophylactic criterion in patients with asymptomatic gallbladder lithiasis.

Introdução: As complicações dos cálculos biliares são uma importante causa de morbidade em nosso país e em todo o mundo e geram altos custos de saúde. Objetivo: O objetivo deste estudo foi determinar quais pacientes com uma complicação de sua patologia de cálculo do ducto biliar (colecistite, colangite aguda, pancreatite aguda) eram previamente assintomáticos, e essa complicação resultou no aparecimento da doença. Local: Sanatório Asociación Española de Socorros Mutuos, Montevidéu - Uruguai. Desenho: Estudo observacional descritivo, retrospectivo, análise de histórias clínicas. Materiais e Métodos: Foram analisados ​​234 casos clínicos. Características epidemiológicas, metodologia diagnóstica, tratamentos recebidos e complicações foram avaliadas neste grupo de pacientes. Resultados: Do total de pacientes (n=234), 109 (46,6%) apresentavam litíase vesicular assintomática e a complicação biliar foi o início da doença. A colecistite aguda foi a complicação mais frequente (68%), seguida da colangite aguda (22%) e a terceira da pancreatite aguda (10%). A idade média de apresentação da doença foi de 59 anos. Conclusões: Quase metade dos pacientes (46,6%) que apresentaram complicação de seus cálculos biliares eram assintomáticos. Esse seria um argumento importante para indicar a colecistectomia laparoscópica com critério profilático em pacientes com litíase vesicular assintomática.

Temperature and salinity effects on whole-organism and cellular level stress responses of the sub-Antarctic notothenioid fish Patagonotothen cornucola yolk-sac larvae.

This work aimed to evaluate the whole-organism and cellular level responses to different combinations of water temperature and salinity of the notothenioid Patagonotothen cornucola at the end of the yolk-sac larval stage. Egg masses of the species were collected in the wild and then maintained at natural water conditions (4 °C and 30 PSU). Newly hatched larvae were placed in aquaria with different combinations of water temperature (4 °C, 12 °C, and 16 °C) and salinity (15 and 30 PSU) during four days before yolk sac absorption. Larvae exposed to 12 °C grew more in length than those exposed to 16 °C, but yolk volume was more reduced in larvae exposed to 16 °C than those exposed to 4 °C and 30 PSU than of 15 PSU. In addition, a higher proportion of larvae exposed to 12 °C and 15 PSU completely absorbed their yolk. Whereas the more tolerant larvae to high temperatures were those exposed to 16 °C and 30 PSU, lipid peroxidation and protein oxidation were highest at natural and at 12 °C and 30 PSU conditions, respectively. The nutritional status (as standardized DNA/RNA index-sRD -) was low in all cases, even at natural conditions (average sRD ~ 1). Our study suggests that, in the context of climate change, the mortality rate of yolk-sac larvae of P. cornucola would not increase due to temperature or salinity stress. However, indirect effects (such as habitat degradation or changes in food availability) would be critical after complete absorption of the yolk.

Similar Frequency and Inducibility of Intact Human Immunodeficiency Virus-1 Proviruses in Blood and Lymph Nodes.

BACKGROUND: The human immunodeficiency virus (HIV)-1 latent reservoir (LR) in resting CD4+ T cells is a barrier to cure. LR measurements are commonly performed on blood samples and therefore may miss latently infected cells residing in tissues, including lymph nodes. METHODS: We determined the frequency of intact HIV-1 proviruses and proviral inducibility in matched peripheral blood (PB) and lymph node (LN) samples from 10 HIV-1-infected patients on antiretroviral therapy (ART) using the intact proviral DNA assay and a novel quantitative viral induction assay. Prominent viral sequences from induced viral RNA were characterized using a next-generation sequencing assay. RESULTS: The frequencies of CD4+ T cells with intact proviruses were not significantly different in PB versus LN (61/106 vs 104/106 CD4+ cells), and they were substantially lower than frequencies of CD4+ T cells with defective proviruses. The frequencies of CD4+ T cells induced to produce high levels of viral RNA were not significantly different in PB versus LN (4.3/106 vs 7.9/106), but they were 14-fold lower than the frequencies of cells with intact proviruses. Sequencing of HIV-1 RNA from induced proviruses revealed comparable sequences in paired PB and LN samples. CONCLUSIONS: These results further support the use of PB as an appropriate proxy for the HIV-1 LR in secondary lymphoid organs.

River ecosystem conceptual models and non-perennial rivers: A critical review.

Conceptual models underpin river ecosystem research. However, current models focus on continuously flowing rivers and few explicitly address characteristics such as flow cessation and drying. The applicability of existing conceptual models to nonperennial rivers that cease to flow (intermittent rivers and ephemeral streams, IRES) has not been evaluated. We reviewed 18 models, finding that they collectively describe main drivers of biogeochemical and ecological patterns and processes longitudinally (upstream-downstream), laterally (channel-riparian-floodplain), vertically (surface water-groundwater), and temporally across local and landscape scales. However, perennial rivers are longitudinally continuous while IRES are longitudinally discontinuous. Whereas perennial rivers have bidirectional lateral connections between aquatic and terrestrial ecosystems, in IRES, this connection is unidirectional for much of the time, from terrestrial-to-aquatic only. Vertical connectivity between surface and subsurface water occurs bidirectionally and is temporally consistent in perennial rivers. However, in IRES, this exchange is temporally variable, and can become unidirectional during drying or rewetting phases. Finally, drying adds another dimension of flow variation to be considered across temporal and spatial scales in IRES, much as flooding is considered as a temporally and spatially dynamic process in perennial rivers. Here, we focus on ways in which existing models could be modified to accommodate drying as a fundamental process that can alter these patterns and processes across spatial and temporal dimensions in streams. This perspective is needed to support river science and management in our era of rapid global change, including increasing duration, frequency, and occurrence of drying.