Need for open data on COVID-19 vaccine uptake among pregnant people in the Caribbean: a call to action.

Pregnant people with coronavirus disease 2019 (COVID-19) have a higher risk of adverse maternal and fetal outcomes compared with pregnant people without COVID-19. In 2021, large increases in maternal mortality were reported in Jamaica, almost half of which were attributable to COVID-19. COVID-19 vaccination has been shown to reduce these risks, but low- and middle-income countries lack free, publicly available data, known as open data, on COVID-19 vaccine uptake for their pregnant populations. The objectives of this paper were to: review how high-income countries use open data to detect trends in COVID-19 vaccine uptake among pregnant people and develop vaccination distribution strategies; outline barriers to making open data available for maternal COVID-19 vaccination in the Caribbean; and propose a multipronged strategy that would increase the availability of open data on maternal COVID-19 vaccination in the Caribbean. A multipronged strategy to fill the data void would involve: (i) utilizing existing Caribbean maternal immunization data collection entities; (ii) adapting digital software tools to establish maternal electronic immunization registries; and (iii) collaborating with local partners skilled in data analytics. Making open data available for COVID-19 vaccine uptake among pregnant people in the Caribbean could offer substantial benefits, including the development of measurable maternal COVID-19 vaccination goals and the facilitation of vaccine decision-making discussions between providers and pregnant people.

Las embarazadas con la enfermedad por coronavirus del 2019 (COVID-19) tienen un mayor riesgo de resultados maternos y fetales adversos que aquellas libres de la enfermedad. En el 2021, en Jamaica se notificó un gran aumento de la mortalidad materna, del cual casi la mitad fue atribuible a la COVID-19. Se ha demostrado que la vacunación contra la COVID-19 reduce tales riesgos, pero los países de ingresos bajos y medianos carecen de datos gratuitos y de carácter público, conocidos como datos abiertos, sobre la aceptación de la vacuna contra la COVID-19 por parte de las mujeres durante el embarazo. Los objetivos del presente artículo consistieron en examinar cómo los países de ingresos altos utilizan los datos abiertos para detectar las tendencias de aceptación de la vacuna contra la COVID-19 entre las mujeres durante el embarazo y formular estrategias de distribución de las vacunas; señalar los obstáculos que dificultan la disponibilidad de los datos abiertos sobre la vacunación materna contra la COVID-19 en el Caribe; y proponer una estrategia múltiple que permita aumentar la disponibilidad de datos abiertos sobre la vacunación materna contra la COVID-19 en el Caribe. Una estrategia múltiple para llenar este vacío de información implicaría: a) utilizar las entidades de recopilación de datos sobre inmunización materna ya existentes en el Caribe; b) adaptar las herramientas informáticas digitales para crear registros electrónicos de vacunación materna; y c) colaborar con asociados locales especializados en el análisis de datos. Facilitar el acceso a los datos abiertos sobre la aceptación de la vacuna contra la COVID-19 entre las mujeres durante el embarazo en el Caribe podría ofrecer beneficios considerables, tales como el establecimiento de objetivos cuantificables en materia de vacunación materna contra la COVID-19, y propiciar las deliberaciones sobre la toma de decisiones en materia de vacunación entre los prestadores de atención de salud y las embarazadas.

Gestantes com a doença pelo coronavírus 2019 (COVID-19) têm maior risco de desfechos maternos e fetais adversos em comparação com gestantes sem COVID-19. Em 2021, foi registrado um aumento acentuado da mortalidade materna na Jamaica, e quase metade era atribuível à COVID-19. Foi demonstrado que a vacinação contra a COVID-19 reduz esses riscos, mas os países de baixa e média renda não dispõem de dados gratuitos e publicamente disponíveis (os chamados dados abertos) sobre a adesão à vacina contra a COVID-19 entre gestantes. Os objetivos deste estudo foram: analisar como os países de alta renda usam dados abertos para detectar tendências na adesão à vacina contra a COVID-19 entre gestantes e desenvolver estratégias de distribuição da vacina; descrever os obstáculos para disponibilizar dados abertos sobre a vacinação materna contra a COVID-19 no Caribe; e propor uma estratégia multifacetada que aumente a disponibilidade de dados abertos sobre a vacinação materna contra a COVID-19 no Caribe. Uma estratégia multifacetada para obter dados a fim de preencher essa lacuna envolveria: (i) utilização das entidades existentes que coletam dados de imunização materna no Caribe; (ii) adaptação de ferramentas de software para estabelecer registros eletrônicos de imunização materna; e (iii) colaboração com parceiros locais especializados em análise de dados. A disponibilização de dados abertos sobre a adesão de gestantes à vacinação contra a COVID-19 no Caribe poderia oferecer benefícios substanciais, incluindo o desenvolvimento de metas mensuráveis de vacinação materna contra a COVID-19, e facilitar discussões entre profissionais de saúde e gestantes para a tomada de decisões sobre vacinas.

Need for open data on COVID-19 vaccine uptake among pregnant people in the Caribbean: a call to action / Necesidad de datos abiertos sobre la aceptación de la vacuna contra la COVID-19 entre las mujeres durante el embarazo en el Caribe: un llamado a la acción

[ABSTRACT]. Pregnant people with coronavirus disease 2019 (COVID-19) have a higher risk of adverse maternal and fetal outcomes compared with pregnant people without COVID-19. In 2021, large increases in maternal mortality were reported in Jamaica, almost half of which were attributable to COVID-19. COVID-19 vaccination has been shown to reduce these risks, but low and middle-income countries lack free, publicly available data, known as open data, on COVID-19 vaccine uptake for their pregnant populations. The objectives of this paper were to: review how high-income countries use open data to detect trends in COVID-19 vaccine uptake among pregnant people and develop vaccination distribution strategies; outline barriers to making open data available for maternal COVID-19 vaccination in the Caribbean; and propose a multipronged strategy that would increase the availability of open data on maternal COVID-19 vaccination in the Caribbean. A multipronged strategy to fill the data void would involve: (i) utilizing existing Caribbean maternal immunization data collection entities; (ii) adapting digital software tools to establish maternal electronic immunization registries; and (iii) collaborating with local partners skilled in data analytics. Making open data available for COVID-19 vaccine uptake among pregnant people in the Caribbean could offer substantial benefits, including the development of measurable maternal COVID-19 vaccination goals and the facilitation of vaccine decision-making discussions between providers and pregnant people.

[RESUMEN]. Las embarazadas con la enfermedad por coronavirus del 2019 (COVID-19) tienen un mayor riesgo de resultados maternos y fetales adversos que aquellas libres de la enfermedad. En el 2021, en Jamaica se notificó un gran aumento de la mortalidad materna, del cual casi la mitad fue atribuible a la COVID-19. Se ha demostrado que la vacunación contra la COVID-19 reduce tales riesgos, pero los países de ingresos bajos y medianos carecen de datos gratuitos y de carácter público, conocidos como datos abiertos, sobre la aceptación de la vacuna contra la COVID-19 por parte de las mujeres durante el embarazo. Los objetivos del presente artículo consistieron en examinar cómo los países de ingresos altos utilizan los datos abiertos para detectar las tendencias de aceptación de la vacuna contra la COVID-19 entre las mujeres durante el embarazo y formular estrategias de distribución de las vacunas; señalar los obstáculos que dificultan la disponibilidad de los datos abiertos sobre la vacunación materna contra la COVID-19 en el Caribe; y proponer una estrategia múltiple que permita aumentar la disponibilidad de datos abiertos sobre la vacunación materna contra la COVID-19 en el Caribe. Una estrategia múltiple para llenar este vacío de información implicaría: a) utilizar las entidades de recopilación de datos sobre inmunización materna ya existentes en el Caribe; b) adaptar las herramientas informáticas digitales para crear registros electrónicos de vacunación materna; y c) colaborar con asociados locales especializados en el análisis de datos. Facilitar el acceso a los datos abiertos sobre la aceptación de la vacuna contra la COVID-19 entre las mujeres durante el embarazo en el Caribe podría ofrecer beneficios considerables, tales como el establecimiento de objetivos cuantificables en materia de vacunación materna contra la COVID-19, y propiciar las deliberaciones sobre la toma de decisiones en materia de vacunación entre los prestadores de atención de salud y las embarazadas.

[RESUMO]. Gestantes com a doença pelo coronavírus 2019 (COVID-19) têm maior risco de desfechos maternos e fetais adversos em comparação com gestantes sem COVID-19. Em 2021, foi registrado um aumento acentuado da mortalidade materna na Jamaica, e quase metade era atribuível à COVID-19. Foi demonstrado que a vacinação contra a COVID-19 reduz esses riscos, mas os países de baixa e média renda não dispõem de dados gratuitos e publicamente disponíveis (os chamados dados abertos) sobre a adesão à vacina contra a COVID-19 entre gestantes. Os objetivos deste estudo foram: analisar como os países de alta renda usam dados abertos para detectar tendências na adesão à vacina contra a COVID-19 entre gestantes e desenvolver estratégias de distribuição da vacina; descrever os obstáculos para disponibilizar dados abertos sobre a vacinação materna contra a COVID-19 no Caribe; e propor uma estratégia multifacetada que aumente a disponibilidade de dados abertos sobre a vacinação materna contra a COVID-19 no Caribe. Uma estratégia multifacetada para obter dados a fim de preencher essa lacuna envolveria: (i) utilização das entidades exis- tentes que coletam dados de imunização materna no Caribe; (ii) adaptação de ferramentas de software para estabelecer registros eletrônicos de imunização materna; e (iii) colaboração com parceiros locais especial- izados em análise de dados. A disponibilização de dados abertos sobre a adesão de gestantes à vacinação contra a COVID-19 no Caribe poderia oferecer benefícios substanciais, incluindo o desenvolvimento de metas mensuráveis de vacinação materna contra a COVID-19, e facilitar discussões entre profissionais de saúde e gestantes para a tomada de decisões sobre vacinas.

Factors Associated With Coronavirus Disease 2019 Vaccine Uptake Among Pregnant Women and Nonpregnant Women of Reproductive Age in Jamaica.

Background: Despite high rates of coronavirus disease 2019 (COVID-19)-related maternal mortality, Jamaica currently has little data on COVID-19 vaccine uptake among pregnant women. Methods: We conducted a cross-sectional, web-based survey of 192 reproductive-aged women in Jamaica from February 1 to 8, 2022. Participants were recruited from a convenience sample of patients, providers, and staff at a teaching hospital. We assessed self-reported COVID-19 vaccination status and COVID-19-related medical mistrust (operationalized as vaccine confidence, government mistrust, and race-based mistrust). We used multivariable modified Poisson regression to test the association between vaccine uptake and pregnancy. Results: Of 192 respondents, 72 (38%) were pregnant. Most (93%) were Black. Vaccine uptake was 35% in pregnant women versus 75% in nonpregnant women. Pregnant women were more likely to cite healthcare providers versus the government as trustworthy sources of COVID-19 vaccine information (65% vs 28%). Pregnancy, low vaccine confidence, and government mistrust were associated with a lower likelihood of COVID-19 vaccination (adjusted prevalence ratio [aPR] = 0.68 [95% confidence interval {CI}, .49-.95], aPR = 0.61 [95% CI, .40-.95], and aPR = 0.68 [95% CI, .52-.89], respectively). Race-based mistrust was not associated with COVID-19 vaccination in the final model. Conclusions: Pregnancy, low vaccine confidence, and government mistrust were associated with a lower likelihood of COVID-19 vaccination among reproductive-aged women in Jamaica. Future studies should evaluate the efficacy of strategies proven to improve maternal vaccination coverage, including standing "opt-out" vaccination orders and collaborative provider and patient-led educational videos tailored for pregnant individuals. Strategies that decouple vaccine messaging from government agencies also warrant evaluation.

Need for open data on COVID-19 vaccine uptake among pregnant people in the Caribbean: a call to action / Necesidad de datos abiertos sobre la aceptación de la vacuna contra la COVID-19 entre las mujeres durante el embarazo en el Caribe: un llamado a la acción / Necessidade de dados abertos sobre a adesão de gestantes à vacinação contra a COVID-19 no Caribe: um chamado à ação

ABSTRACT Pregnant people with coronavirus disease 2019 (COVID-19) have a higher risk of adverse maternal and fetal outcomes compared with pregnant people without COVID-19. In 2021, large increases in maternal mortality were reported in Jamaica, almost half of which were attributable to COVID-19. COVID-19 vaccination has been shown to reduce these risks, but low- and middle-income countries lack free, publicly available data, known as open data, on COVID-19 vaccine uptake for their pregnant populations. The objectives of this paper were to: review how high-income countries use open data to detect trends in COVID-19 vaccine uptake among pregnant people and develop vaccination distribution strategies; outline barriers to making open data available for maternal COVID-19 vaccination in the Caribbean; and propose a multipronged strategy that would increase the availability of open data on maternal COVID-19 vaccination in the Caribbean. A multipronged strategy to fill the data void would involve: (i) utilizing existing Caribbean maternal immunization data collection entities; (ii) adapting digital software tools to establish maternal electronic immunization registries; and (iii) collaborating with local partners skilled in data analytics. Making open data available for COVID-19 vaccine uptake among pregnant people in the Caribbean could offer substantial benefits, including the development of measurable maternal COVID-19 vaccination goals and the facilitation of vaccine decision-making discussions between providers and pregnant people.

RESUMEN Las embarazadas con la enfermedad por coronavirus del 2019 (COVID-19) tienen un mayor riesgo de resultados maternos y fetales adversos que aquellas libres de la enfermedad. En el 2021, en Jamaica se notificó un gran aumento de la mortalidad materna, del cual casi la mitad fue atribuible a la COVID-19. Se ha demostrado que la vacunación contra la COVID-19 reduce tales riesgos, pero los países de ingresos bajos y medianos carecen de datos gratuitos y de carácter público, conocidos como datos abiertos, sobre la aceptación de la vacuna contra la COVID-19 por parte de las mujeres durante el embarazo. Los objetivos del presente artículo consistieron en examinar cómo los países de ingresos altos utilizan los datos abiertos para detectar las tendencias de aceptación de la vacuna contra la COVID-19 entre las mujeres durante el embarazo y formular estrategias de distribución de las vacunas; señalar los obstáculos que dificultan la disponibilidad de los datos abiertos sobre la vacunación materna contra la COVID-19 en el Caribe; y proponer una estrategia múltiple que permita aumentar la disponibilidad de datos abiertos sobre la vacunación materna contra la COVID-19 en el Caribe. Una estrategia múltiple para llenar este vacío de información implicaría: a) utilizar las entidades de recopilación de datos sobre inmunización materna ya existentes en el Caribe; b) adaptar las herramientas informáticas digitales para crear registros electrónicos de vacunación materna; y c) colaborar con asociados locales especializados en el análisis de datos. Facilitar el acceso a los datos abiertos sobre la aceptación de la vacuna contra la COVID-19 entre las mujeres durante el embarazo en el Caribe podría ofrecer beneficios considerables, tales como el establecimiento de objetivos cuantificables en materia de vacunación materna contra la COVID-19, y propiciar las deliberaciones sobre la toma de decisiones en materia de vacunación entre los prestadores de atención de salud y las embarazadas.

RESUMO Gestantes com a doença pelo coronavírus 2019 (COVID-19) têm maior risco de desfechos maternos e fetais adversos em comparação com gestantes sem COVID-19. Em 2021, foi registrado um aumento acentuado da mortalidade materna na Jamaica, e quase metade era atribuível à COVID-19. Foi demonstrado que a vacinação contra a COVID-19 reduz esses riscos, mas os países de baixa e média renda não dispõem de dados gratuitos e publicamente disponíveis (os chamados dados abertos) sobre a adesão à vacina contra a COVID-19 entre gestantes. Os objetivos deste estudo foram: analisar como os países de alta renda usam dados abertos para detectar tendências na adesão à vacina contra a COVID-19 entre gestantes e desenvolver estratégias de distribuição da vacina; descrever os obstáculos para disponibilizar dados abertos sobre a vacinação materna contra a COVID-19 no Caribe; e propor uma estratégia multifacetada que aumente a disponibilidade de dados abertos sobre a vacinação materna contra a COVID-19 no Caribe. Uma estratégia multifacetada para obter dados a fim de preencher essa lacuna envolveria: (i) utilização das entidades existentes que coletam dados de imunização materna no Caribe; (ii) adaptação de ferramentas de software para estabelecer registros eletrônicos de imunização materna; e (iii) colaboração com parceiros locais especializados em análise de dados. A disponibilização de dados abertos sobre a adesão de gestantes à vacinação contra a COVID-19 no Caribe poderia oferecer benefícios substanciais, incluindo o desenvolvimento de metas mensuráveis de vacinação materna contra a COVID-19, e facilitar discussões entre profissionais de saúde e gestantes para a tomada de decisões sobre vacinas.

Characteristics of wastewater originating from dental practices using predominantly mercury-free dental materials.

Dental materials are currently undergoing a revolution. Mercury use, including traditional amalgam (mercury-containing) material used in dental fillings, is now being widely regulated under the Minamata convention, and dental amalgam is currently being replaced by resin formulations in dentistry. These resin-based materials can be tuned to offer varying material properties by incorporation of a range of nano- and micro-particle based 'fillers' for different dental properties and applications. However, these innovations may have a concomitant effect on the waste streams associated with common dental applications, in particular the potential for higher concentrations of novel micro- and nanomaterials within wastewater streams, and a potential route for novel nanomaterials into the wider Environment. These new materials may also mean that wastewater filtering apparatus commonly deployed at present, such as amalgam separators, may be less efficient or insufficient to capture these new filler materials in dental facility wastewater. In this work, we analyse dental wastewater streams from three dental facilities in Ireland with differing amalgam separators in place. The potential overall toxicity, particulate load and physicochemical properties are analysed. The overall risk posed by these new materials is also discussed.

Mind the gap: primary care physicians and gynecologists' knowledge about menopause and their attitudes to hormone therapy use in Jamaica.

OBJECTIVES: The study objective was to evaluate physicians' knowledge, attitude, and practices toward menopause and hormone therapy. METHODS: This study was a cross-sectional study using a stratified sample of physicians across the four health regions in Jamaica, between September and October 2017. A total of 145 physicians (75% response rate) completed a questionnaire to assess knowledge and attitudes toward menopause and prescribing hormonal therapy. Univariate and bivariate analyses were used to describe and compare the knowledge, attitudes, and practices in participants. RESULTS: The majority of physicians (66%) self-reported a moderate level of knowledge of menopausal treatment options. Self-reported knowledge was associated with years in practice (P < 0.0001) and level of experience (P < 0.0001). Those who identified as having good and moderate knowledge were likely to discuss treatment options with patients (P < 0.005), while physicians with good knowledge were more likely to prescribe hormone therapy (P < 0.05). Correct responses regarding common menopause symptoms were noted in >60% physicians; however, there was a precipitous fall in correct responses regarding findings related to the Women's Health Initiative (<45%). More consultant grade physicians were confident and less confused about prescribing hormone therapy (P < 0.05) compared to junior grade physicians. When stratified by level of experience, knowledge level was the factor that discouraged physicians from seeing symptomatic menopausal patients (P < 0.05). CONCLUSIONS: This study highlights the gaps in knowledge and practices and a need for carefully designed curricula to provide individualized, risk-mitigated training in menopause healthcare.

Video Summary:http://links.lww.com/MENO/A814 .

Automated Writing Assessments Measure Undergraduate Learning after Completion of a Computer-Based Cellular Respiration Tutorial.

The focus of biology education has shifted from memorization to conceptual understanding of core biological concepts such as matter and energy relationships. To examine undergraduate learning about matter and energy, we incorporated constructed-response (CR) questions into an interactive computer-based tutorial. The objective of this tutorial is to teach students about matter and energy and help dispel common misconceptions through the context of cellular respiration. We used a constructed-response classifier (CRC) tool to categorize ideas in responses to three CR questions and measure changes in student thinking about cellular respiration. Our data set includes 841 undergraduates from 19 geographically diverse institutions including two-year colleges, primarily undergraduate institutions, and research-intensive colleges and universities. We found students from all institution types included more scientific ideas in CRs post-tutorial. Students used an average of 2.1 ideas in CRs and frequently used both scientific and developing ideas. We found this mixed thinking persisted after the tutorial regardless of institution type. Students' multiple-choice (MC) selections were correlated with their CRs, but CRs revealed more mixed thinking than would be inferred from MC responses. Our study shows a CRC tool can measure student learning after a computer-based tutorial and provides more complete information than MC responses.

Introductory biology undergraduate students' mixed ideas about genetic information flow.

The core concept of genetic information flow was identified in recent calls to improve undergraduate biology education. Previous work shows that students have difficulty differentiating between the three processes of the Central Dogma (CD; replication, transcription, and translation). We built upon this work by developing and applying an analytic coding rubric to 1050 student written responses to a three-question item about the CD. Each response was previously coded only for correctness using a holistic rubric. Our rubric captures subtleties of student conceptual understanding of each process that previous work has not yet captured at a large scale. Regardless of holistic correctness scores, student responses included five or six distinct ideas. By analyzing common co-occurring rubric categories in student responses, we found a common pair representing two normative ideas about the molecules produced by each CD process. By applying analytic coding to student responses preinstruction and postinstruction, we found student thinking about the processes involved was most prone to change. The combined strengths of analytic and holistic rubrics allow us to reveal mixed ideas about the CD processes and provide a detailed picture of which conceptual ideas students draw upon when explaining each CD process.

Mixed Student Ideas about Mechanisms of Human Weight Loss.

Recent calls for college biology education reform have identified "pathways and transformations of matter and energy" as a big idea in biology crucial for students to learn. Previous work has been conducted on how college students think about such matter-transforming processes; however, little research has investigated how students connect these ideas. Here, we probe student thinking about matter transformations in the familiar context of human weight loss. Our analysis of 1192 student constructed responses revealed three scientific (which we label "Normative") and five less scientific (which we label "Developing") ideas that students use to explain weight loss. Additionally, students combine these ideas in their responses, with an average number of 2.19 ± 1.07 ideas per response, and 74.4% of responses containing two or more ideas. These results highlight the extent to which students hold multiple (both correct and incorrect) ideas about complex biological processes. We described student responses as conforming to either Scientific, Mixed, or Developing descriptive models, which had an average of 1.9 ± 0.6, 3.1 ± 0.9, and 1.7 ± 0.8 ideas per response, respectively. Such heterogeneous student thinking is characteristic of difficulties in both conceptual change and early expertise development and will require careful instructional intervention for lasting learning gains.

Wobble pairs of the HDV ribozyme play specific roles in stabilization of active site dynamics.

The hepatitis delta virus (HDV) is the only known human pathogen whose genome contains a catalytic RNA motif (ribozyme). The overall architecture of the HDV ribozyme is that of a double-nested pseudoknot, with two GU pairs flanking the active site. Although extensive studies have shown that mutation of either wobble results in decreased catalytic activity, little work has focused on linking these mutations to specific structural effects on catalytic fitness. Here we use molecular dynamics simulations based on an activated structure to probe the active site dynamics as a result of wobble pair mutations. In both wild-type and mutant ribozymes, the in-line fitness of the active site (as a measure of catalytic proficiency) strongly depends on the presence of a C75(N3H3+)N1(O5') hydrogen bond, which positions C75 as the general acid for the reaction. Our mutational analyses show that each GU wobble supports catalytically fit conformations in distinct ways; the reverse G25U20 wobble promotes high in-line fitness, high occupancy of the C75(N3H3+)G1(O5') general-acid hydrogen bond and stabilization of the G1U37 wobble, while the G1U37 wobble acts more locally by stabilizing high in-line fitness and the C75(N3H3+)G1(O5') hydrogen bond. We also find that stable type I A-minor and P1.1 hydrogen bonding above and below the active site, respectively, prevent local structural disorder from spreading and disrupting global conformation. Taken together, our results define specific, often redundant architectural roles for several structural motifs of the HDV ribozyme active site, expanding the known roles of these motifs within all HDV-like ribozymes and other structured RNAs.

Disparate HDV ribozyme crystal structures represent intermediates on a rugged free-energy landscape.

The hepatitis delta virus (HDV) ribozyme is a member of the class of small, self-cleaving catalytic RNAs found in a wide range of genomes from HDV to human. Both pre- and post-catalysis (precursor and product) crystal structures of the cis-acting genomic HDV ribozyme have been determined. These structures, together with extensive solution probing, have suggested that a significant conformational change accompanies catalysis. A recent crystal structure of a trans-acting precursor, obtained at low pH and by molecular replacement from the previous product conformation, conforms to the product, raising the possibility that it represents an activated conformer past the conformational change. Here, using fluorescence resonance energy transfer (FRET), we discovered that cleavage of this ribozyme at physiological pH is accompanied by a structural lengthening in magnitude comparable to previous trans-acting HDV ribozymes. Conformational heterogeneity observed by FRET in solution appears to have been removed upon crystallization. Analysis of a total of 1.8 µsec of molecular dynamics (MD) simulations showed that the crystallographically unresolved cleavage site conformation is likely correctly modeled after the hammerhead ribozyme, but that crystal contacts and the removal of several 2'-oxygens near the scissile phosphate compromise catalytic in-line fitness. A cis-acting version of the ribozyme exhibits a more dynamic active site, while a G-1 residue upstream of the scissile phosphate favors poor fitness, allowing us to rationalize corresponding changes in catalytic activity. Based on these data, we propose that the available crystal structures of the HDV ribozyme represent intermediates on an overall rugged RNA folding free-energy landscape.