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1.
Clin Transplant ; 38(1): e15181, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37922213

RESUMEN

INTRODUCTION: The data on post-transplant cyclophosphamide (PTCy) in pediatric acute leukemia after matched allo-HSCT are limited to case series. The present study aimed to assess the results of PTCy-based GVHD prophylaxis in a large cohort of children with acute leukemia after matched allo-HSCT. METHODS: A retrospective analysis of 190 pediatric patients with acute leukemia who had a first allograft between 2008 and 2020 from a matched sibling donor (MSD) or matched unrelated donor (MUD) was carried out. In the MSD setting, GVHD prophylaxis consisted of PTCy alone (n = 28) for the study group, and calcineurin inhibitor (CNI) ± antimetabolite (n = 30) for the control group. In MUD setting, most patients in the study group received GVHD prophylaxis with PTCy+CNI+mycophenolate mofetil (n = 42, 66.7%) or PTCy+CNI+sirolimus (n = 12, 19%). All patients (n = 69) in the control group received ATG+CNI+antimetabolite. RESULTS: After MUD allo-HSCT, the incidences of acute GVHD grade III-IV and moderate/severe chronic GVHD were significantly lower in the PTCy group compared to control (6.6% vs. 35.0% and 12.7% vs. 47.1%, respectively, p < .0001). Five-year GVHD-free, relapse-free survival (GRFS) after MUD allo-HSCT was higher in the PTCy group compared to control (35.1% vs. 7.3%, p < .0001). At the same time, there was no significant difference between both groups after MSD allo-HSCT. CONCLUSIONS: In pediatric acute leukemia, PTCy-based GVHD prophylaxis for MUD allo-HSCT is a feasible and effective option that results in a low incidence of GVHD. Compared to the ATG-based approach, PTCy provides better control of GVHD in children. In pediatric allo-HSCT from MSD, PTCy demonstrates comparable effectiveness to conventional GVHD prophylaxis.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Humanos , Niño , Estudios Retrospectivos , Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide Aguda/terapia , Ciclofosfamida/uso terapéutico , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Ácido Micofenólico/uso terapéutico , Enfermedad Aguda , Inhibidores de la Calcineurina/uso terapéutico , Antimetabolitos/uso terapéutico , Donante no Emparentado
2.
Int J Mol Sci ; 24(10)2023 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-37239953

RESUMEN

A theory of the evolutionary role of hereditary tumors, or the carcino-evo-devo theory, is being developed. The main hypothesis of the theory, the hypothesis of evolution by tumor neofunctionalization, posits that hereditary tumors provided additional cell masses during the evolution of multicellular organisms for the expression of evolutionarily novel genes. The carcino-evo-devo theory has formulated several nontrivial predictions that have been confirmed in the laboratory of the author. It also suggests several nontrivial explanations of biological phenomena previously unexplained by the existing theories or incompletely understood. By considering three major types of biological development-individual, evolutionary, and neoplastic development-within one theoretical framework, the carcino-evo-devo theory has the potential to become a unifying biological theory.


Asunto(s)
Evolución Biológica , Biología Evolutiva
3.
Biophys J ; 121(6): 897-909, 2022 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-35176272

RESUMEN

Since the pioneering work of Thomas Gold, published in 1948, it has been known that we owe our sensitive sense of hearing to a process in the inner ear that can amplify incident sounds on a cycle-by-cycle basis. Called the active process, it uses energy to counteract the viscous dissipation associated with sound-evoked vibrations of the ear's mechanotransduction apparatus. Despite its importance, the mechanism of the active process and the proximate source of energy that powers it have remained elusive, especially at the high frequencies characteristic of amniote hearing. This is partly due to our insufficient understanding of the mechanotransduction process in hair cells, the sensory receptors and amplifiers of the inner ear. It has been proposed previously that cyclical binding of Ca2+ ions to individual mechanotransduction channels could power the active process. That model, however, relied on tailored reaction rates that structurally forced the direction of the cycle. Here we ground our study on our previous model of hair-cell mechanotransduction, which relied on cooperative gating of pairs of channels, and incorporate into it the cyclical binding of Ca2+ ions. With a single binding site per channel and reaction rates drawn from thermodynamic principles, the current model shows that hair cells behave as nonlinear oscillators that exhibit Hopf bifurcations, dynamical instabilities long understood to be signatures of the active process. Using realistic parameter values, we find bifurcations at frequencies in the kilohertz range with physiological Ca2+ concentrations. The current model relies on the electrochemical gradient of Ca2+ as the only energy source for the active process and on the relative motion of cooperative channels within the stereociliary membrane as the sole mechanical driver. Equipped with these two mechanisms, a hair bundle proves capable of operating at frequencies in the kilohertz range, characteristic of amniote hearing.


Asunto(s)
Células Ciliadas Auditivas , Mecanotransducción Celular , Oído , Audición/fisiología , Mecanotransducción Celular/fisiología , Viscosidad
4.
Proc Natl Acad Sci U S A ; 114(51): E11010-E11019, 2017 12 19.
Artículo en Inglés | MEDLINE | ID: mdl-29217640

RESUMEN

Mechanoelectrical transduction in the inner ear is a biophysical process underlying the senses of hearing and balance. The key players involved in this process are mechanosensitive ion channels. They are located in the stereocilia of hair cells and opened by the tension in specialized molecular springs, the tip links, connecting adjacent stereocilia. When channels open, the tip links relax, reducing the hair-bundle stiffness. This gating compliance makes hair cells especially sensitive to small stimuli. The classical explanation for the gating compliance is that the conformational rearrangement of a single channel directly shortens the tip link. However, to reconcile theoretical models based on this mechanism with experimental data, an unrealistically large structural change of the channel is required. Experimental evidence indicates that each tip link is a dimeric molecule, associated on average with two channels at its lower end. It also indicates that the lipid bilayer modulates channel gating, although it is not clear how. Here, we design and analyze a model of mechanotransduction where each tip link attaches to two channels, mobile within the membrane. Their states and positions are coupled by membrane-mediated elastic forces arising from the interaction between the channels' hydrophobic cores and that of the lipid bilayer. This coupling induces cooperative opening and closing of the channels. The model reproduces the main properties of hair-cell mechanotransduction using only realistic parameters constrained by experimental evidence. This work provides an insight into the fundamental role that membrane-mediated ion-channel cooperativity can play in sensory physiology.


Asunto(s)
Células Ciliadas Auditivas/fisiología , Activación del Canal Iónico , Canales Iónicos/metabolismo , Membrana Dobles de Lípidos/metabolismo , Mecanotransducción Celular , Algoritmos , Calcio/metabolismo , Cinética , Modelos Biológicos
5.
Biophys J ; 117(8): 1536-1548, 2019 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-31585704

RESUMEN

Hearing relies on the conversion of mechanical stimuli into electrical signals. In vertebrates, this process of mechanoelectrical transduction (MET) is performed by specialized receptors of the inner ear, the hair cells. Each hair cell is crowned by a hair bundle, a cluster of microvilli that pivot in response to sound vibrations, causing the opening and closing of mechanosensitive ion channels. Mechanical forces are projected onto the channels by molecular springs called tip links. Each tip link is thought to connect to a small number of MET channels that gate cooperatively and operate as a single transduction unit. Pushing the hair bundle in the excitatory direction opens the channels, after which they rapidly reclose in a process called fast adaptation. It has been experimentally observed that the hair cell's biophysical properties mature gradually during postnatal development: the maximal transduction current increases, sensitivity sharpens, transduction occurs at smaller hair-bundle displacements, and adaptation becomes faster. Similar observations have been reported during tip-link regeneration after acoustic damage. Moreover, when measured at intermediate developmental stages, the kinetics of fast adaptation varies in a given cell, depending on the magnitude of the imposed displacement. The mechanisms underlying these seemingly disparate observations have so far remained elusive. Here, we show that these phenomena can all be explained by the progressive addition of MET channels of constant properties, which populate the hair bundle first as isolated entities and then progressively as clusters of more sensitive, cooperative MET channels. As the proposed mechanism relies on the difference in biophysical properties between isolated and clustered channels, this work highlights the importance of cooperative interactions between mechanosensitive ion channels for hearing.


Asunto(s)
Células Ciliadas Auditivas/metabolismo , Canales Iónicos/metabolismo , Mecanotransducción Celular , Modelos Neurológicos , Animales , Diferenciación Celular , Células Ciliadas Auditivas/citología , Activación del Canal Iónico , Ratones
6.
Proc Natl Acad Sci U S A ; 113(5): 1441-6, 2016 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-26787894

RESUMEN

High-level neurons processing complex, behaviorally relevant signals are sensitive to conjunctions of features. Characterizing the receptive fields of such neurons is difficult with standard statistical tools, however, and the principles governing their organization remain poorly understood. Here, we demonstrate multiple distinct receptive-field features in individual high-level auditory neurons in a songbird, European starling, in response to natural vocal signals (songs). We then show that receptive fields with similar characteristics can be reproduced by an unsupervised neural network trained to represent starling songs with a single learning rule that enforces sparseness and divisive normalization. We conclude that central auditory neurons have composite receptive fields that can arise through a combination of sparseness and normalization in neural circuits. Our results, along with descriptions of random, discontinuous receptive fields in the central olfactory neurons in mammals and insects, suggest general principles of neural computation across sensory systems and animal classes.


Asunto(s)
Corteza Auditiva/fisiología , Neuronas/fisiología , Animales , Corteza Auditiva/citología
7.
Nature ; 474(7351): 376-9, 2011 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-21602823

RESUMEN

The detection of sound begins when energy derived from an acoustic stimulus deflects the hair bundles on top of hair cells. As hair bundles move, the viscous friction between stereocilia and the surrounding liquid poses a fundamental physical challenge to the ear's high sensitivity and sharp frequency selectivity. Part of the solution to this problem lies in the active process that uses energy for frequency-selective sound amplification. Here we demonstrate that a complementary part of the solution involves the fluid-structure interaction between the liquid within the hair bundle and the stereocilia. Using force measurement on a dynamically scaled model, finite-element analysis, analytical estimation of hydrodynamic forces, stochastic simulation and high-resolution interferometric measurement of hair bundles, we characterize the origin and magnitude of the forces between individual stereocilia during small hair-bundle deflections. We find that the close apposition of stereocilia effectively immobilizes the liquid between them, which reduces the drag and suppresses the relative squeezing but not the sliding mode of stereociliary motion. The obliquely oriented tip links couple the mechanotransduction channels to this least dissipative coherent mode, whereas the elastic horizontal top connectors that stabilize the structure further reduce the drag. As measured from the distortion products associated with channel gating at physiological stimulation amplitudes of tens of nanometres, the balance of viscous and elastic forces in a hair bundle permits a relative mode of motion between adjacent stereocilia that encompasses only a fraction of a nanometre. A combination of high-resolution experiments and detailed numerical modelling of fluid-structure interactions reveals the physical principles behind the basic structural features of hair bundles and shows quantitatively how these organelles are adapted to the needs of sensitive mechanotransduction.


Asunto(s)
Cilios/fisiología , Fricción/fisiología , Células Ciliadas Auditivas/citología , Células Ciliadas Auditivas/fisiología , Rana catesbeiana/fisiología , Animales , Análisis de Elementos Finitos , Mecanotransducción Celular/fisiología , Modelos Biológicos , Procesos Estocásticos , Viscosidad
8.
Proc Natl Acad Sci U S A ; 109(8): 2896-901, 2012 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-22328158

RESUMEN

The ear detects sounds so faint that they produce only atomic-scale displacements in the mechanoelectrical transducer, yet thermal noise causes fluctuations larger by an order of magnitude. Explaining how hearing can operate when the magnitude of the noise greatly exceeds that of the signal requires an understanding both of the transducer's micromechanics and of the associated noise. Using microrheology, we characterize the statistics of this noise; exploiting the fluctuation-dissipation theorem, we determine the associated micromechanics. The statistics reveal unusual Brownian motion in which the mean square displacement increases as a fractional power of time, indicating that the mechanisms governing energy dissipation are related to those of energy storage. This anomalous scaling contradicts the canonical model of mechanoelectrical transduction, but the results can be explained if the micromechanics incorporates viscoelasticity, a salient characteristic of biopolymers. We amend the canonical model and demonstrate several consequences of viscoelasticity for sensory coding.


Asunto(s)
Oído/fisiología , Elasticidad/fisiología , Mecanotransducción Celular/fisiología , Movimiento (Física) , Animales , Anuros/fisiología , Fenómenos Biomecánicos/fisiología , Difusión , Módulo de Elasticidad/fisiología , Células Ciliadas Auditivas/fisiología , Células Ciliadas Auditivas/ultraestructura , Activación del Canal Iónico , Modelos Lineales , Modelos Biológicos , Sáculo y Utrículo/ultraestructura , Temperatura , Viscosidad
9.
J Neurophysiol ; 111(6): 1183-9, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24353301

RESUMEN

Recognition of natural stimuli requires a combination of selectivity and invariance. Classical neurobiological models achieve selectivity and invariance, respectively, by assigning to each cortical neuron either a computation equivalent to the logical "AND" or a computation equivalent to the logical "OR." One powerful OR-like operation is the MAX function, which computes the maximum over input activities. The MAX function is frequently employed in computer vision to achieve invariance and considered a key operation in visual cortex. Here we explore the computations for selectivity and invariance in the auditory system of a songbird, using natural stimuli. We ask two related questions: does the MAX operation exist in auditory system? Is it implemented by specialized "MAX" neurons, as assumed in vision? By analyzing responses of individual neurons to combinations of stimuli we systematically sample the space of implemented feature recombination functions. Although we frequently observe the MAX function, we show that the same neurons that implement it also readily implement other operations, including the AND-like response. We then show that sensory adaptation, a ubiquitous property of neural circuits, causes transitions between these operations in individual neurons, violating the fixed neuron-to-computation mapping posited in the state-of-the-art object-recognition models. These transitions, however, accord with predictions of neural-circuit models incorporating divisive normalization and variable polynomial nonlinearities at the spike threshold. Because these biophysical properties are not tied to a particular sensory modality but are generic, the flexible neuron-to-computation mapping demonstrated in this study in the auditory system is likely a general property.


Asunto(s)
Percepción Auditiva , Neuronas/fisiología , Patrones de Reconocimiento Fisiológico , Adaptación Fisiológica , Animales , Encéfalo/citología , Encéfalo/fisiología , Femenino , Masculino , Modelos Neurológicos , Estorninos/fisiología
10.
AIDS Behav ; 17(3): 1016-24, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22987210

RESUMEN

The study examined the efficacy of a brief theory-based counseling intervention to reduce sexual HIV risk behaviors among STI clinic patients in St. Petersburg, Russia. Men and women (n = 307) were recruited to receive either: (1) a 60-minute motivational/skills-building counseling session dealing with sexual HIV risk reduction, or (2) written HIV prevention information material. Participants completed baseline, three- and six-month assessments in the period between July 2009 and May 2011. Compared to the control group, the face-to-face counseling intervention showed significant increases in the percentage of condom use and consistent condom use, and significant decreases in the number of unprotected sexual acts and frequency of drug use before sex. Intervention effects dissipated by 6 months. The brief counseling intervention may effectively reduce HIV sexual risk behaviors and enhance protective behaviors among STI clinic patients in Russia. Short-term positive effects were achieved with a single one hour counseling session.


Asunto(s)
Instituciones de Atención Ambulatoria , Consejo , Infecciones por VIH/prevención & control , Conducta Sexual/psicología , Enfermedades de Transmisión Sexual/prevención & control , Adolescente , Adulto , Condones/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Conducta de Reducción del Riesgo , Asunción de Riesgos , Federación de Rusia , Trastornos Relacionados con Sustancias/epidemiología , Resultado del Tratamiento , Sexo Inseguro/estadística & datos numéricos , Adulto Joven
11.
AIDS Behav ; 17(3): 1144-50, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22139416

RESUMEN

We investigated whether inebriation was associated with having non-main partners and unprotected sex with non-main partners and whether drinking motivations were associated with sexual risk behaviors among patients attending an STD clinic in St Petersburg, Russia. A cross-sectional behavior survey was applied to 362 participants between 2008 and 2009. Multivariate logistic regression was used for analysis. At-risk drinking per Alcohol Use Disorders Identification Test (AUDIT-C) criteria (OR 2.5, 95% CI 1.4-4.4) was independently associated with having non-main sexual partners. Inebriation (OR 3.2, 95% CI 1.3-8.1) but not at-risk drinking or drinking prior to sex was associated with unprotected sex with non-main partners. Among drinkers, the consumption of alcohol to facilitate sexual encounters (OR 2.7, 95% CI 1.6-4.5) was associated with having non-main sexual partners. HIV prevention programs in Russia must address inebriation in addition to conventional patterns of problem drinking such as those measured by AUDIT-C and consider individuals' motivations to drink that lead to sexual risk taking.


Asunto(s)
Consumo de Bebidas Alcohólicas/efectos adversos , Intoxicación Alcohólica/epidemiología , Motivación , Asunción de Riesgos , Conducta Sexual/estadística & datos numéricos , Adulto , Consumo de Bebidas Alcohólicas/epidemiología , Instituciones de Atención Ambulatoria , Femenino , Infecciones por VIH/prevención & control , Humanos , Masculino , Federación de Rusia , Enfermedades de Transmisión Sexual/prevención & control , Encuestas y Cuestionarios , Sexo Inseguro/estadística & datos numéricos , Adulto Joven
12.
AIDS Behav ; 17(7): 2510-20, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23881187

RESUMEN

We evaluated the efficacy of a peer-educator network intervention as a strategy to reduce HIV acquisition among injection drug users (IDUs) and their drug and/or sexual networks. A randomized controlled trial was conducted in St. Petersburg, Russia among IDU index participants and their risk network participants. Network units were randomized to the control or experimental intervention. Only the experimental index participants received training sessions to communicate risk reduction techniques to their network members. Analysis includes 76 index and 84 network participants who were HIV uninfected. The main outcome measure was HIV sero-conversion. The incidence rates in the control and experimental groups were 19.57 (95 % CI 10.74-35.65) and 7.76 (95 % CI 3.51-17.19) cases per 100 p/y, respectively. The IRR was 0.41 (95 % CI 0.15-1.08) without a statistically significant difference between the two groups (log rank test statistic X(2) = 2.73, permutation p value = 0.16). Retention rate was 67 % with a third of the loss due to incarceration or death. The results show a promising trend that this strategy would be successful in reducing the acquisition of HIV among IDUs.


Asunto(s)
Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Educación en Salud , Grupo Paritario , Abuso de Sustancias por Vía Intravenosa/complicaciones , Abuso de Sustancias por Vía Intravenosa/epidemiología , Serodiagnóstico del SIDA , Adulto , Western Blotting , Comunicación , Estudios Transversales , Ensayo de Inmunoadsorción Enzimática , Femenino , Estudios de Seguimiento , Seronegatividad para VIH , Humanos , Masculino , Conducta de Reducción del Riesgo , Federación de Rusia , Apoyo Social , Sexo Inseguro/prevención & control , Sexo Inseguro/estadística & datos numéricos
13.
Prev Sci ; 14(4): 400-10, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23322231

RESUMEN

Cultural adaptation is an important step in the process of implementing health promotion interventions that, having been proven to be effective in one culture, are being applied in another. This study describes the results of a formative investigation to culturally adapt a STI/HIV risk reduction intervention for use in St. Petersburg, Russia. Analyses of data from brief elicitation interviews, focus groups, community experts, and a pilot test of the adapted intervention identified environmental, cognitive-information processing, and affect-motivation factors that needed to be addressed during the adaptation process. The participant/counselor relationship was adapted to reflect a hierarchical (cf. collaborative) relationship in order to accommodate Russian expectations about patient interactions with healthcare experts. Key skills building activities (e.g., identification of personal risk behaviors, role-playing) were approached gradually or indirectly in order to maintain participants' engagement in the intervention, and close-ended questions were added to assist participants in understanding unfamiliar concepts such as "triggers" and self-efficacy. Information about the prevalence of HIV/STI infections and alcohol use included data specific to St. Petersburg to increase the personal relevance of these materials and messages. Intervention components were tailored to participants' risk reduction and informational needs. No gender differences that would have justified adaptation of the intervention approach or content were noted. Examples of specific adaptations and the key issues to attend to when adapting behavioral interventions for use in Russian clinical settings are discussed.


Asunto(s)
Adaptación Psicológica , Características Culturales , Asunción de Riesgos , Conducta Sexual , Enfermedades de Transmisión Sexual/prevención & control , Instituciones de Atención Ambulatoria , Humanos , Federación de Rusia
14.
J Fam Plann Reprod Health Care ; 39(3): 179-85, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23377534

RESUMEN

OBJECTIVES: To assess risk for unintended pregnancy, this study describes the correlates of unprotected sexual intercourse (UPSI) among women who inject illicit drugs or who have sexual partners who inject drugs in St Petersburg, Russia. METHODS: Data from a cross-sectional survey and biological test results collected between 2005 and 2008 from 202 Russian women (143 drug injectors and 59 non-drug injectors) were analysed. Multivariate regression was used to investigate the correlates of UPSI occurring at the women's last sexual act. Independent variables included socio-demographics, age at sexual debut, first sexual encounter perceived as involuntary, number of pregnancies and number of children for which the participant is the primary caretaker, heavy sporadic drinking (i.e. consuming more than five drinks in 2 hours at least twice a month), at-risk drinking per the Alcohol Use Disorder Identification Test (AUDIT-C) score, and sexually transmitted infections (HIV-1, syphilis serology, Chlamydia trachomatis and Neisseria gonorrheae). RESULTS: Sixty-seven percent of women reported UPSI at last intercourse. UPSI was independently associated with heavy sporadic drinking [odds ratio (OR) 2.8, 95% CI 1.2-6.6] and having been pregnant (OR 2.25, 95% CI 1.1-4.6). CONCLUSIONS: Despite the high risk for HIV acquisition or transmission and unintended pregnancy, condom use among the study population is low. Programmes to investigate and improve contraceptive use, including condom use, among this vulnerable group of women are needed. Such programmes may require identifying and targeting female reproductive health concerns and problem drinking, particularly heavy sporadic drinking, rather than conventional measures of alcohol misuse.


Asunto(s)
Parejas Sexuales , Abuso de Sustancias por Vía Intravenosa , Sexo Inseguro , Adulto , Intervalos de Confianza , Estudios Transversales , Femenino , Seropositividad para VIH , Humanos , Análisis Multivariante , Oportunidad Relativa , Embarazo , Embarazo no Planeado , Investigación Cualitativa , Federación de Rusia , Adulto Joven
15.
Harm Reduct J ; 10: 15, 2013 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-24006958

RESUMEN

BACKGROUND: The majority of HIV-infected individuals requiring antiretroviral therapy (ART) in Russia are Injection Drug Users (IDU). Substitution therapy used as part of a comprehensive harm reduction program is unavailable in Russia. Past data shows that only 16% of IDU receiving substance abuse treatment completed the course without relapse, and only 40% of IDU on ART remained on treatment at 6 months. Our goal was to determine if it was feasible to improve these historic outcomes by adding intensive case management (ICM) to the substance abuse and ART treatment programs for IDU. METHODS: IDU starting ART and able to involve a "supporter" who would assist in their treatment plan were enrolled. ICM included opiate detoxification, bi-monthly contact and counseling with the case, weekly group sessions, monthly contact with the "supporter" and home visits as needed. Full follow- up (FFU) was 8 months. Stata v10 (College Station, TX) was used for all analysis. Descriptive statistics were calculated for all baseline demographic variables, baseline and follow-up CD4 count, and viral load. Median baseline and follow-up CD4 counts and RNA levels were compared using the Kruskal-Wallis test. The proportion of participants with RNA < 1000 copies mL at baseline and follow-up was compared using Fisher's Exact test. McNemar's test for paired proportions was used to compare the change in proportion of participants with RNA < 1000 copies mL from baseline to follow-up. RESULTS: Between November 2007 and December 2008, 60 IDU were enrolled. 34 (56.7%) were male. 54/60 (90.0%) remained in FFU. Overall, 31/60 (52%) were active IDU at enrollment and 27 (45%) were active at their last follow-up visit. 40/60 (66.7%) attended all of their ART clinic visits, 13/60 (21.7%) missed one or more visit but remained on ART, and 7/60 (11.7%) stopped ART before the end of FFU. Overall, 39/53 (74%) had a final 6-8 month HIV RNA viral load (VL) < 1000 copies/mL. CONCLUSIONS: Despite no substitution therapy to assist IDU in substance abuse and ART treatment programs, ICM was feasible, and the retention and adherence of IDU on ART in St. Petersburg could be greatly enhanced by adding ICM to the existing treatment programs.


Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Cuidados Críticos/métodos , Infecciones por VIH/tratamiento farmacológico , Abuso de Sustancias por Vía Intravenosa/rehabilitación , Adolescente , Adulto , Recuento de Linfocito CD4 , Manejo de Caso/organización & administración , Consejo , Estudios de Factibilidad , Femenino , Humanos , Masculino , Cumplimiento de la Medicación , Estudios Prospectivos , ARN Viral/sangre , Federación de Rusia , Resultado del Tratamiento , Carga Viral , Adulto Joven
16.
Int J Mycobacteriol ; 12(3): 305-309, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37721237

RESUMEN

Background: The nutrient medium effects on the quality of the matrix-assisted laser desorption/ionization-time-of-flight (MALDI-ToF) mass spectra. The standard library includes spectra of microorganisms of the family Mycobacteriaceae grown on the Lowenstein-Jensen and Middlebrook Media. There are new methods for culturing microorganisms from this group, including inoculation on chromogenic media. Methods: The study included 240 strains of NTM isolated from patients during tuberculosis examination. The inoculation of the biological material was carried out on solid culture media of Lowenstein-Jensen and universal chromogenic media. Identification of bacteria from both types of media was performed by MALDI-ToF mass spectrometry (Bruker Daltonik GmbH, Germany). Analysis of protein spectra was performed. Results: For all strains, the spectra revealed both coinciding peaks (regardless of the cultivation medium) and significant differences, including the complete absence of some peaks depending on the medium. The results of a greater divergence of peaks in mass and intensity were obtained for slow-growing species than for fast-growing species. For all analyzed cultures, the number of peaks in the mass spectra was significantly higher when cultivating on a universal chromogenic medium than on a Lowenstein-Jensen medium. Conclusions: The use for NTM cultivation of a universal chromogenic medium makes it possible to obtain acceptable identification results by MALDI-ToF mass spectrometry using a standard library.


Asunto(s)
Mycobacteriaceae , Humanos , Medios de Cultivo/química , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Nutrientes , Rayos Láser
17.
J Physiol ; 590(2): 301-8, 2012 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-22124150

RESUMEN

Direct gating of mechanoelectrical transduction channels by mechanical force is a basic feature of hair cells that assures fast transduction and underpins the mechanical amplification of acoustic inputs, but the associated non-linearity - the gating compliance - inevitably distorts signals. Because reducing distortion would make the ear a better detector, we sought mechanisms with that effect. Mimicking in vivo stimulation, we used stiff probes to displace individual hair bundles at physiological amplitudes and measured the coherence and phase of the relative stereociliary motions with a dual-beam differential interferometer. Although stereocilia moved coherently and in phase at the stimulus frequencies, large phase lags at the frequencies of the internally generated distortion products indicated dissipative relative motions. Tip links engaged these relative modes and decreased the coherence in both stimulated and free hair bundles. These results show that a hair bundle breaks into a highly dissipative serial arrangement of stereocilia at distortion frequencies, precluding their amplification.


Asunto(s)
Estimulación Acústica , Células Ciliadas Auditivas Internas/fisiología , Distorsión de la Percepción/fisiología , Estereocilios/fisiología , Animales , Femenino , Activación del Canal Iónico/fisiología , Canales Iónicos/fisiología , Masculino , Mecanorreceptores/fisiología , Modelos Animales , Rana catesbeiana
18.
AIDS Behav ; 16(2): 334-9, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21448729

RESUMEN

We conducted a cross-sectional study to determine whether the time between two consecutive sexual partnerships (gap) is associated with sexually transmitted infections (STIs) in Russia. A self-administered questionnaire was administered to STI clinic patients in St. Petersburg and participant's STI data at the time of enrollment in the study was collected from medical charts. The length of the gap between partnerships was divided into four categories: overlapping (0 or negative gap), short gaps (1-90 days), mid-length gaps (91-365 days), and long gaps (366 days or more). Among the 659 respondents, 22.6% had overlapping partnerships, and 13.7, 4.2, and 59.5% had short, mid-length and long gaps, respectively. Short gaps (OR 2.34; 95% CI 1.38-3.95), but not overlapping relationships, were independently associated with STIs when contrasted against long term gaps. HIV prevention programs for Russian STI clinic patients should therefore focus also on prolonging the gap between consecutive, monogamous sexual partnerships.


Asunto(s)
Infecciones por VIH/epidemiología , Conducta Sexual/estadística & datos numéricos , Enfermedades de Transmisión Sexual/epidemiología , Enfermedades de Transmisión Sexual/transmisión , Adolescente , Adulto , Condones/estadística & datos numéricos , Estudios Transversales , Femenino , Infecciones por VIH/prevención & control , Promoción de la Salud , Humanos , Masculino , Factores de Riesgo , Federación de Rusia/epidemiología , Parejas Sexuales , Encuestas y Cuestionarios , Adulto Joven
19.
AIDS Behav ; 16(6): 1597-604, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21800183

RESUMEN

This study investigates whether age at first alcoholic drink is associated with sexual risk behaviors among injection drug users (IDUs) and non-IDUs who are sexual partners of IDUs in St. Petersburg, Russia. A path analysis was used to test a model of age at first drink, age at sexual debut, age at first drug use, current substance use patterns and current sexual risk behaviors among 558 participants. Results revealed that age at first drink had an effect on multiple sex partners through age at sexual debut and injection drug use, but no effect on unprotected sex. Age at first drug use was not related to sexual risk behaviors. Investigation of age of drinking onset may provide useful information for programs to reduce sexual risk behaviors and injection drug use. Different paths leading to unprotected sex and multiple sexual partners call for different approaches to reduce sexual risk behaviors among this population.


Asunto(s)
Consumo de Bebidas Alcohólicas/epidemiología , Infecciones por VIH/epidemiología , Conducta Sexual/estadística & datos numéricos , Parejas Sexuales , Abuso de Sustancias por Vía Intravenosa/epidemiología , Adolescente , Adulto , Factores de Edad , Consumidores de Drogas , Femenino , Infecciones por VIH/transmisión , Humanos , Entrevistas como Asunto , Masculino , Persona de Mediana Edad , Asunción de Riesgos , Federación de Rusia/epidemiología , Factores Socioeconómicos , Encuestas y Cuestionarios , Adulto Joven
20.
J Trauma Stress ; 25(1): 86-93, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22328312

RESUMEN

Whether intimate partner violence (IPV) perpetration and victimization are associated with human immunodeficiency virus (HIV) risk behaviors is seldom investigated in Russia. The present study hypothesized that patients from a sexually transmitted infection center in Russia who perpetrated IPV or were victims of IPV would be more likely to have HIV risk behaviors including injection drug use, multiple partners, and inconsistent condom use than those who were not involved with IPV. We used a self-administered questionnaire to collect information from 381 patients on demographics, health status, injection drug use, sexual behaviors, and violence involving sexual partners between 2008 and 2009. After including sociodemographics, lifetime IPV perpetration was significantly associated with having had multiple sexual partners among male patients (odds ratio [OR] = 2.61, p < .05). IPV victimization was significantly associated with injection drug use among male and female patients (OR = 5.22, p < .05) and with inconsistent condom use among female patients (OR = 8.93, p < .05). IPV perpetration and victimization were common among male and female study participants and were associated with greater HIV risk behaviors. HIV prevention programs in Russia should address the risks associated with IPV among people at risk for HIV.


Asunto(s)
Víctimas de Crimen , Infecciones por VIH/etiología , Asunción de Riesgos , Parejas Sexuales , Violencia , Femenino , Humanos , Masculino , Federación de Rusia , Encuestas y Cuestionarios , Sexo Inseguro/psicología , Adulto Joven
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