Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 46
Filtrar
1.
J Med Chem ; 67(17): 15620-15675, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39172133

RESUMO

Acinetobacter baumannii, a commonly multidrug-resistant Gram-negative bacterium responsible for large numbers of bloodstream and lung infections worldwide, is increasingly difficult to treat and constitutes a growing threat to human health. Structurally novel antibacterial chemical matter that can evade existing resistance mechanisms is essential for addressing this critical medical need. Herein, we describe our efforts to inhibit the essential A. baumannii lipooligosaccharide (LOS) ATP-binding cassette (ABC) transporter MsbA. An unexpected impurity from a phenotypic screening was optimized as a series of dimeric compounds, culminating with 1 (cerastecin D), which exhibited antibacterial activity in the presence of human serum and a pharmacokinetic profile sufficient to achieve efficacy against A. baumannii in murine septicemia and lung infection models.


Assuntos
Transportadores de Cassetes de Ligação de ATP , Infecções por Acinetobacter , Acinetobacter baumannii , Antibacterianos , Proteínas de Bactérias , Lipopolissacarídeos , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/metabolismo , Antibacterianos/farmacologia , Antibacterianos/química , Animais , Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/antagonistas & inibidores , Camundongos , Humanos , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/metabolismo , Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores , Transportadores de Cassetes de Ligação de ATP/metabolismo , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/microbiologia , Testes de Sensibilidade Microbiana
2.
NPJ Microgravity ; 10(1): 51, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38704360

RESUMO

Human Wharton's jelly stem cells (hWJSCs) are multipotent stem cells that are extensively employed in biotechnology applications. However, the impact of simulated lunar microgravity (sµG) on the growth, differentiation, and viability of this cell population is incompletely characterized. We aimed to determine whether acute (72 h) exposure to sµG elicited changes in growth and lineage differentiation in hWJSCs and if putative changes were maintained once exposure to terrestrial gravity (1.0 G) was restored. hWJSCs were cultured under standard 1.0 G conditions prior to being passaged and cultured under sµG (0.16 G) using a random positioning machine. Relative to control, hWJSCs cultured under sµG exhibited marked reductions in growth but not viability. Cell population expression of characteristic stemness markers (CD 73, 90, 105) was significantly reduced under sµG conditions. hWJSCs had 308 significantly upregulated and 328 significantly downregulated genes when compared to 1.0 G culture conditions. Key markers of cell replication, including MKI67, were inhibited. Significant upregulation of osteocyte-chondrocyte lineage markers, including SERPINI1, MSX2, TFPI2, BMP6, COMP, TMEM119, LUM, HGF, CHI3L1 and SPP1, and downregulation of cell fate regulators, including DNMT1 and EZH2, were detected in sµG-exposed hWJSCs. When returned to 1.0 G for 3 days, sµG-exposed hWJSCs had accelerated growth, and expression of stemness markers increased, approaching normal (i.e. 95%) levels. Our data support earlier findings that acute sµG significantly reduces the cell division potential of hWJSCs and suggest that acute sµG-exposure induces reversible changes in cell growth accompanied by osteocyte-chondrocyte changes in lineage differentiation.

3.
West J Emerg Med ; 25(3): 320-324, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38801036

RESUMO

Introduction: Bystander provision of naloxone is a key modality to reduce opioid overdose-related death. Naloxone training courses are available, but no standardized program exists. As part of a bystander empowerment course, we created and evaluated a brief naloxone training module. Methods: This was a retrospective evaluation of a naloxone training course, which was paired with Stop the Bleed training for hemorrhage control and was offered to administrative staff in an office building. Participants worked in an organization related to healthcare, but none were clinicians. The curriculum included the following topics: 1) background about the opioid epidemic; 2) how to recognize the signs of an opioid overdose; 3) actions not to take when encountering an overdose victim; 4) the correct steps to take when encountering an overdose victim; 5) an overview of naloxone products; and 6) Good Samaritan protection laws. The 20-minute didactic section was followed by a hands-on session with nasal naloxone kits and a simulation mannequin. The course was evaluated with the Opioid Overdose Knowledge (OOKS) and Opioid Overdose Attitudes (OOAS) scales for take-home naloxone training evaluation. We used the paired Wilcoxon signed-rank test to compare scores pre- and post-course. Results: Twenty-eight participants completed the course. The OOKS, measuring objective knowledge about opioid overdose and naloxone, had improved scores from a median of 73.2% (interquartile range [IQR] 68.3%-79.9%) to 91.5% (IQR 85.4%-95.1%), P < 0.001. The three domains on the OOAS score also showed statistically significant results. Competency to manage an overdose improved on a five-point scale from a median of 2.5 (IQR 2.4-2.9) to a median of 3.7 (IQR 3.5-4.1), P < 0.001. Concerns about managing an overdose decreased (improved) from a median of 2.3 (IQR 1.9-2.6) to median 1.8 (IQR 1.5-2.1), P < 0.001. Readiness to intervene in an opioid overdose improved from a median of 4 (IQR 3.8-4.2) to a median of 4.2 (IQR 4-4.2), P < 0.001. Conclusion: A brief course designed to teach bystanders about opioid overdose and naloxone was feasible and effective. We encourage hospitals and other organizations to use and promulgate this model. Furthermore, we suggest the convening of a national consortium to achieve consensus on program content and delivery.


Assuntos
Naloxona , Antagonistas de Entorpecentes , Naloxona/uso terapêutico , Humanos , Antagonistas de Entorpecentes/uso terapêutico , Estudos Retrospectivos , Masculino , Feminino , Overdose de Drogas/prevenção & controle , Overdose de Drogas/tratamento farmacológico , Overdose de Opiáceos/prevenção & controle , Adulto , Avaliação de Programas e Projetos de Saúde , Currículo , Conhecimentos, Atitudes e Prática em Saúde , Pessoa de Meia-Idade
4.
Eur Heart J Case Rep ; 8(4): ytae128, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38567279

RESUMO

Background: Giant cell myocarditis (GCM) is an inflammatory form of acute heart failure with high rates of cardiac transplantation or death. Standard acute treatment includes multi-drug immunosuppressive regimens. There is a small but growing number of case reports utilizing rabbit anti-thymocyte globulin in severe cases. Case summary: Two cases are presented with similar presentations and clinical courses. Both are middle-aged patients with no significant past medical history, who presented with new acute decompensated heart failure that quickly progressed to cardiogenic shock requiring inotropic and mechanical circulatory support. Both underwent endomyocardial biopsies that diagnosed GCM. Both were treated with a multi-agent immunosuppressive regimen, notably including rabbit anti-thymocyte globulin, with subsequent resolution of shock and recovery of left ventricular ejection fraction. Both remain transplant-free and without ventricular arrhythmias at 7 months and 26 months, respectively. Discussion: In aggregate, these cases are typical of GCM. They add to growing observational data that upfront rabbit anti-thymocyte globulin may reduce morbidity and mortality in GCM, including potentially preventing the need for complex interventions like orthotopic heart transplantation.

5.
Cell Rep ; 43(3): 113872, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38427562

RESUMO

Infection, autoimmunity, and cancer are principal human health challenges of the 21st century. Often regarded as distinct ends of the immunological spectrum, recent studies hint at potential overlap between these diseases. For example, inflammation can be pathogenic in infection and autoimmunity. T resident memory (TRM) cells can be beneficial in infection and cancer. However, these findings are limited by size and scope; exact immunological factors shared across diseases remain elusive. Here, we integrate large-scale deeply clinically and biologically phenotyped human cohorts of 526 patients with infection, 162 with lupus, and 11,180 with cancer. We identify an NKG2A+ immune bias as associative with protection against disease severity, mortality, and autoimmune/post-acute chronic disease. We reveal that NKG2A+ CD8+ T cells correlate with reduced inflammation and increased humoral immunity and that they resemble TRM cells. Our results suggest NKG2A+ biases as a cross-disease factor of protection, supporting suggestions of immunological overlap between infection, autoimmunity, and cancer.


Assuntos
Doenças Autoimunes , Doenças Transmissíveis , Neoplasias , Humanos , Linfócitos T CD8-Positivos , Neoplasias/patologia , Autoimunidade , Inflamação/patologia , Doenças Autoimunes/patologia , Doenças Transmissíveis/patologia , Memória Imunológica
6.
United European Gastroenterol J ; 12(4): 496-503, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38412024

RESUMO

BACKGROUND: Faecal incontinence is a common debilitating condition associated with poor quality of life that generates substantial economic strain on healthcare systems. OBJECTIVES: We aimed to evaluate, in a tertiary referral population presenting with faecal incontinence, the impact of suffering additional disorders of gut-brain interaction (DGBI) on symptom severity, anxiety, depression and quality of life. METHODS: Design: Retrospective cohort study. SETTING: Tertiary referral Neurogastroenterology centre. PATIENTS: All patients presenting with faecal incontinence from 2007 to 2020 were included. MAIN OUTCOME MEASURES: The results from structured medical and surgical questionnaires including Rome III Integrative Questionnaire, Faecal Incontinence Severity Index, Hospital Anxiety and Depression Scale, SF-36, and anorectal physiology were analysed using Stata version 17. Patients were categorised into 3 groups: 0-1 additional DGBI, 2 DGBIs, and 3+ DGBI. Statistical significance was defined as p < 0.05 (two-tailed). KEY RESULTS: Faecal incontinence patients (n = 249; mean age 63.4 ± 12.6 years; 93.6% female, 48.1% urge subtype) met diagnostic criteria for mean 2.2 additional DGBI each, mostly affecting bowel (n = 231, 42.4%) and anorectal (n = 150, 27.5%) regions. A greater number of DGBIs was associated with higher faecal incontinence symptom severity (p < 0.001), higher anxiety (p = 0.002) and depression (p = 0.003), and worse quality of life in areas of mental health (p = 0.037) and social effect (p < 0.001). Patients with a greater number of concurrent DGBI demonstrated a greater family history of gastrointestinal problems (p = 0.004). There were no associations found between a greater amount of DGBIs and anorectal physiology. CONCLUSIONS AND INFERENCES: A greater number of additional DGBIs in faecal incontinence patients was associated with worse faecal incontinence symptoms, higher anxiety and depression scores, and worse quality of life but was unrelated to physiology. This highlights the need to proactively search for comorbid DGBI in patients presenting with faecal incontinence.


Assuntos
Ansiedade , Eixo Encéfalo-Intestino , Depressão , Incontinência Fecal , Qualidade de Vida , Índice de Gravidade de Doença , Humanos , Incontinência Fecal/psicologia , Incontinência Fecal/epidemiologia , Incontinência Fecal/etiologia , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ansiedade/etiologia , Ansiedade/epidemiologia , Ansiedade/diagnóstico , Depressão/etiologia , Depressão/diagnóstico , Depressão/epidemiologia , Idoso , Inquéritos e Questionários
7.
Res Sq ; 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37886475

RESUMO

Infection, autoimmunity, and cancer are the principal human health challenges of the 21st century and major contributors to human death and disease. Often regarded as distinct ends of the immunological spectrum, recent studies have hinted there may be more overlap between these diseases than appears. For example, pathogenic inflammation has been demonstrated as conserved between infection and autoimmune settings. T resident memory (TRM) cells have been highlighted as beneficial for infection and cancer. However, these findings are limited by patient number and disease scope; exact immunological factors shared across disease remain elusive. Here, we integrate large-scale deeply clinically and biologically phenotyped human cohorts of 526 patients with infection, 162 with lupus, and 11,180 with cancer. We identify an NKG2A+ immune bias as associative with protection against disease severity, mortality, and autoimmune and post-acute chronic disease. We reveal that NKG2A+ CD8+ T cells correlate with reduced inflammation, increased humoral immunity, and resemble TRM cells. Our results suggest that an NKG2A+ bias is a pan-disease immunological factor of protection and thus supports recent suggestions that there is immunological overlap between infection, autoimmunity, and cancer. Our findings underscore the promotion of an NKG2A+ biased response as a putative therapeutic strategy.

8.
Am J Obstet Gynecol ; 229(2): 172.e1-172.e12, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37088277

RESUMO

BACKGROUND: Natural language processing is a form of artificial intelligence that allows human users to interface with a machine without using complex codes. The ability of natural language processing systems, such as ChatGPT, to successfully engage with healthcare systems requiring fluid reasoning, specialist data interpretation, and empathetic communication in an unfamiliar and evolving environment is poorly studied. This study investigated whether the ChatGPT interface could engage with and complete a mock objective structured clinical examination simulating assessment for membership of the Royal College of Obstetricians and Gynaecologists. OBJECTIVE: This study aimed to determine whether ChatGPT, without additional training, would achieve a score at least equivalent to that achieved by human candidates who sat for virtual objective structured clinical examinations in Singapore. STUDY DESIGN: This study was conducted in 2 phases. In the first phase, a total of 7 structured discussion questions were selected from 2 historical cohorts (cohorts A and B) of objective structured clinical examination questions. ChatGPT was examined using these questions and responses recorded in a script. Of note, 2 human candidates (acting as anonymizers) were examined on the same questions using videoconferencing, and their responses were transcribed verbatim into written scripts. The 3 sets of response scripts were mixed, and each set was allocated to 1 of 3 human actors. In the second phase, actors were used to presenting these scripts to examiners in response to the same examination questions. These responses were blind scored by 14 qualified examiners. ChatGPT scores were unblinded and compared with historical human candidate performance scores. RESULTS: The average score given to ChatGPT by 14 examiners was 77.2%. The average historical human score (n=26 candidates) was 73.7 %. ChatGPT demonstrated sizable performance improvements over the average human candidate in several subject domains. The median time taken for ChatGPT to complete each station was 2.54 minutes, well before the 10 minutes allowed. CONCLUSION: ChatGPT generated factually accurate and contextually relevant structured discussion answers to complex and evolving clinical questions based on unfamiliar settings within a very short period. ChatGPT outperformed human candidates in several knowledge areas. Not all examiners were able to discern between human and ChatGPT responses. Our data highlight the emergent ability of natural language processing models to demonstrate fluid reasoning in unfamiliar environments and successfully compete with human candidates that have undergone extensive specialist training.


Assuntos
Ginecologia , Obstetrícia , Humanos , Ginecologia/educação , Obstetrícia/educação , Inteligência Artificial , Competência Clínica , Avaliação Educacional
9.
Am J Speech Lang Pathol ; 32(3): 1252-1274, 2023 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-36961960

RESUMO

PURPOSE: Ultrasound biofeedback therapy (UBT) is a relatively new type of technology-assisted speech-language therapy and has shown promise in remediating speech sound disorders. However, there is a current lack of understanding of the barriers and benefits that may influence the usage behavior and clinical decision making for the implementation of UBT from a clinician perspective. In this qualitative study, we explore the perspectives of speech-language pathologists (SLPs) who have used ultrasound biofeedback in programs of speech sound therapy using the unified theory of acceptance and use of technology (UTAUT) model. METHOD: Seven SLPs who had clinical experience treating speech sound disorders with UBT participated. Semistructured in-depth interviews were conducted and video-recorded. Two coders coded and categorized the transcribed data, with consensus established with a third coder. Using thematic analysis, the data were exploratorily grouped into themes along components of the UTAUT model. RESULTS: The highest number of codes was sorted into the "effort expectancy" theme, followed by "performance expectancy," "social influence," and "facilitating conditions" themes of the UTAUT model. Clinicians identified multiple perceived barriers and benefits to the use of ultrasound technology. The top identified barrier was limited accessibility, and the top benefit was the ability to visualize a client's articulatory response to cues on a display. CONCLUSIONS: Clinicians prioritized "effort expectancy" and "performance expectancy" when reflecting on the use of ultrasound biofeedback for speech sound disorders. Clinicians spoke favorably about using UBT for speech sound disorder treatment but acknowledged institutional barriers and limitations at organizational and social levels.


Assuntos
Transtornos da Comunicação , Transtorno Fonológico , Patologia da Fala e Linguagem , Humanos , Transtorno Fonológico/terapia , Biorretroalimentação Psicológica , Ultrassonografia , Fonoterapia , Fala
10.
Clin Linguist Phon ; 37(2): 196-222, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35254181

RESUMO

Ultrasound biofeedback therapy (UBT), which incorporates real-time imaging of tongue articulation, has demonstrated generally positive speech remediation outcomes for individuals with residual speech sound disorder (RSSD). However, UBT requires high attentional demands and may therefore benefit from a simplified display of articulation targets that are easily interpretable and can be compared to real-time articulation. Identifying such targets requires automatic quantification and analysis of movement features relevant to accurate speech production. Our image-analysis program TonguePART automatically quantifies tongue movement as tongue part displacement trajectories from midsagittal ultrasound videos of the tongue, with real-time capability. The present study uses such displacement trajectories to compare accurate and misarticulated American-English rhotic /ɑr/ productions from 40 children, with degree of accuracy determined by auditory perceptual ratings. To identify relevant features of accurate articulation, support vector machine (SVM) classifiers were trained and evaluated on several candidate data representations. Classification accuracy was up to 85%, indicating that quantification of tongue part displacement trajectories captured tongue articulation characteristics that distinguish accurate from misarticulated production of /ɑr/. Regression models for perceptual ratings were also compared. The simplest data representation that retained high predictive ability, demonstrated by high classification accuracy and strong correlation between observed and predicted ratings, was displacements at the midpoint of /r/ relative to /ɑ/ for the tongue dorsum and blade. This indicates that movements of the dorsum and blade are especially relevant to accurate production of /r/, suggesting that a predictive parameter and biofeedback target based on this data representation may be usable for simplified UBT.


Assuntos
Transtornos da Articulação , Transtorno Fonológico , Criança , Humanos , Transtorno Fonológico/diagnóstico por imagem , Transtorno Fonológico/terapia , Fala , Ultrassonografia/métodos , Língua/diagnóstico por imagem , Biorretroalimentação Psicológica/métodos , Fonética
13.
Trop Med Infect Dis ; 7(10)2022 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-36288013

RESUMO

Introduction: Schistosomiasis, a neglected tropical disease (NTD), remains a public health problem in Ethiopia. Freshwater snails, acting as intermediate hosts, release cercariae, the infectious parasite, into the water, which penetrate human skin that encounters infested waters. The objective of this study was to map snail abundance along rivers and study its association with schistosomiasis infection in communities using these rivers. Materials and Methods: A cross-sectional study was carried out at 20 river sites in Mizan Aman city administration, Bench Sheko zone, South West Ethiopia Peoples (SWEP) region, Ethiopia, to study the distribution of host snails and transmission sites for intestinal schistosomiasis. This study used a quantitative database consisting of data on the prevalence of infected snails, the characteristics of rivers and riverbanks, and the prevalence of schistosomiasis in the community, based on stool samples collected from community members near the sampling sites. Results: Aquatic snails were found in 11 of the 20 sites sampled. A total of 598 snails was collected, including Biomphalaria pfeifferi, Biomphalaria sudanica, Radix natalensis and Bulinus globosus species; the most abundant species was Biomphalaria pfeifferi. Stool samples were collected from 206 community members from all 20 sites. Forty-one (19.9%) were positive for Schistosoma mansoni. A positive correlation was found between the presence of snails and positive stool samples (r = 0.60, p = 0.05) and between the presence of infected snails and the prevalence of infection (r = 0.64, p = 0.03). Locations with muddy riverbanks were associated with the presence of snails (r = 0.81, p < 0.001). Conclusions: These results emphasize the importance of mapping snails for the control of schistosomiasis by defining hotspots of infection and identifying factors associated with the presence of infected snails. The results support the need for a continuous mapping of snails and the introduction of snail control as a major element for the successful control of schistosomiasis in endemic communities.

14.
Chaos ; 32(1): 013109, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35105137

RESUMO

This work investigates experimentally and numerically frontal polymerization in a thermally anisotropic system with parallel copper strips embedded in 1,6-hexanediol diacrylate resin. Both experiments and multiphysics finite element analyses reveal that the front propagation in the thermally anisotropic system is orientation-dependent, leading to variations in the front shape and the front velocity due to the different front-metal strip interaction mechanisms along and across the metal strips. The parameters entering the cure kinetics model used in this work are chosen to capture the key characteristics of the polymerization front, i.e., the front temperature and velocity. Numerical parametric analyses demonstrate that the front velocity in the directions parallel and perpendicular to the metal strips increases as the system size decreases and approaches the analytical prediction for homogenized systems. A two-dimensional homogenized model for anisotropic frontal polymerization in the metal-resin system is proposed.

15.
Cell ; 185(5): 881-895.e20, 2022 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-35216672

RESUMO

Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data and patient-reported symptoms. We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific auto-antibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8+ T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes, exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time, leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies.


Assuntos
COVID-19/complicações , COVID-19/diagnóstico , Convalescença , Imunidade Adaptativa/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/sangue , Biomarcadores/metabolismo , Proteínas Sanguíneas/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , COVID-19/imunologia , COVID-19/patologia , COVID-19/virologia , Progressão da Doença , Feminino , Humanos , Imunidade Inata/genética , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Transcriptoma , Adulto Jovem , Síndrome de COVID-19 Pós-Aguda
16.
Prenat Diagn ; 41(8): 1018-1035, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34191294

RESUMO

There are over 50 SARS-CoV-2 candidate vaccines undergoing Phase II and III clinical trials. Several vaccines have been approved by regulatory authorities and rolled out for use in different countries. Due to concerns of potential teratogenicity or adverse effect on maternal physiology, pregnancy has been a specific exclusion criterion for most vaccine trials with only two trials not excluding pregnant women. Thus, other than limited animal studies, gradually emerging development and reproductive toxicity data, and observational data from vaccine registries, there is a paucity of reliable information to guide recommendations for the safe vaccination of pregnant women. Pregnancy is a risk factor for severe COVID-19, especially in women with comorbidities, resulting in increased rates of preterm birth and maternal morbidity. We discuss the major SARS-CoV-2 vaccines, their mechanisms of action, efficacy, safety profile and possible benefits to the maternal-fetal dyad to create a rational approach towards maternal vaccination while anticipating and mitigating vaccine-related complications. Pregnant women with high exposure risks or co-morbidities predisposing to severe COVID-19 infection should be prioritised for vaccination. Those with risk factors for adverse effects should be counselled accordingly. It is essential to support patient autonomy by shared decision-making involving a risk-benefit discussion with the pregnant woman.


Assuntos
Vacinas contra COVID-19 , COVID-19/prevenção & controle , Complicações Infecciosas na Gravidez/prevenção & controle , SARS-CoV-2/imunologia , COVID-19/imunologia , Feminino , Humanos , Gravidez , Complicações Infecciosas na Gravidez/imunologia , Vacinação/ética
17.
Cell ; 183(6): 1479-1495.e20, 2020 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-33171100

RESUMO

We present an integrated analysis of the clinical measurements, immune cells, and plasma multi-omics of 139 COVID-19 patients representing all levels of disease severity, from serial blood draws collected during the first week of infection following diagnosis. We identify a major shift between mild and moderate disease, at which point elevated inflammatory signaling is accompanied by the loss of specific classes of metabolites and metabolic processes. Within this stressed plasma environment at moderate disease, multiple unusual immune cell phenotypes emerge and amplify with increasing disease severity. We condensed over 120,000 immune features into a single axis to capture how different immune cell classes coordinate in response to SARS-CoV-2. This immune-response axis independently aligns with the major plasma composition changes, with clinical metrics of blood clotting, and with the sharp transition between mild and moderate disease. This study suggests that moderate disease may provide the most effective setting for therapeutic intervention.


Assuntos
COVID-19 , Genômica , RNA-Seq , SARS-CoV-2 , Análise de Célula Única , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/sangue , COVID-19/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/imunologia , SARS-CoV-2/metabolismo , Índice de Gravidade de Doença
18.
Molecules ; 25(17)2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32887445

RESUMO

Schistosomiasis, a neglected tropical disease of medical and veterinary importance, transmitted through specific freshwater snail intermediate hosts, is targeted for elimination in several endemic regions in sub-Saharan Africa. Multi-disciplinary methods are required for both human and environmental diagnostics to certify schistosomiasis elimination when eventually reached. Molecular xenomonitoring protocols, a DNA-based detection method for screening disease vectors, have been developed and trialed for parasites transmitted by hematophagous insects, such as filarial worms and trypanosomes, yet few have been extensively trialed or proven reliable for the intermediate host snails transmitting schistosomes. Here, previously published universal and Schistosoma-specific internal transcribed spacer (ITS) rDNA primers were adapted into a triplex PCR primer assay that allowed for simple, robust, and rapid detection of Schistosoma haematobium and Schistosoma bovis in Bulinus snails. We showed this two-step protocol could sensitively detect DNA of a single larval schistosome from experimentally infected snails and demonstrate its functionality for detecting S. haematobium infections in wild-caught snails from Zanzibar. Such surveillance tools are a necessity for succeeding in and certifying the 2030 control and elimination goals set by the World Health Organization.


Assuntos
Bioensaio/métodos , Interações Hospedeiro-Parasita , Schistosoma haematobium/isolamento & purificação , Esquistossomose/parasitologia , Caramujos/parasitologia , Xenobióticos/metabolismo , Animais , Simulação por Computador , Polimorfismo de Nucleotídeo Único/genética
19.
Best Pract Res Clin Endocrinol Metab ; 34(4): 101439, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32616466

RESUMO

Overt hypothyroidism is a common endocrine disorder affecting 1-2% of women of reproductive age. Optimizing treatment in pregnant women with overt hypothyroidism can reduce adverse fetal and maternal outcomes. Ideally, women who are known to have a history of hypothyroidism or those with risk factors for becoming hypothyroid, should have adequate preconception care to ensure euthyroidism from the onset of pregnancy, with a TSH target of below 2.5mIU/L. On women who are already on levothyroxine, an empirical dose increase of 30-50% as soon as pregnancy is confirmed may be considered. During pregnancy, levothyroxine doses should be titrated against TSH, which have trimester-specific ranges. In women who are known to be hypothyroid but are inadequately treated, we recommend a doubling of levothyroxine dose on at least three days a week to rapidly achieve euthyroidism. In newly diagnosed overt hypothyroidism in pregnancy, starting doses of either 100 or 150 mg daily may be considered safe.


Assuntos
Hipotireoidismo/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Tiroxina/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Humanos , Hipotireoidismo/epidemiologia , Gravidez , Complicações na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Fatores de Risco , Tireotropina/uso terapêutico
20.
Am J Obstet Gynecol ; 222(6): 521-531, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32217113

RESUMO

The current coronavirus disease 2019 (COVID-19) pneumonia pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading globally at an accelerated rate, with a basic reproduction number (R0) of 2-2.5, indicating that 2-3 persons will be infected from an index patient. A serious public health emergency, it is particularly deadly in vulnerable populations and communities in which healthcare providers are insufficiently prepared to manage the infection. As of March 16, 2020, there are more than 180,000 confirmed cases of COVID-19 worldwide, with more than 7000 related deaths. The SARS-CoV-2 virus has been isolated from asymptomatic individuals, and affected patients continue to be infectious 2 weeks after cessation of symptoms. The substantial morbidity and socioeconomic impact have necessitated drastic measures across all continents, including nationwide lockdowns and border closures. Pregnant women and their fetuses represent a high-risk population during infectious disease outbreaks. To date, the outcomes of 55 pregnant women infected with COVID-19 and 46 neonates have been reported in the literature, with no definite evidence of vertical transmission. Physiological and mechanical changes in pregnancy increase susceptibility to infections in general, particularly when the cardiorespiratory system is affected, and encourage rapid progression to respiratory failure in the gravida. Furthermore, the pregnancy bias toward T-helper 2 (Th2) system dominance, which protects the fetus, leaves the mother vulnerable to viral infections, which are more effectively contained by the Th1 system. These unique challenges mandate an integrated approach to pregnancies affected by SARS-CoV-2. Here we present a review of COVID-19 in pregnancy, bringing together the various factors integral to the understanding of pathophysiology and susceptibility, diagnostic challenges with real-time reverse transcription polymerase chain reaction (RT-PCR) assays, therapeutic controversies, intrauterine transmission, and maternal-fetal complications. We discuss the latest options in antiviral therapy and vaccine development, including the novel use of chloroquine in the management of COVID-19. Fetal surveillance, in view of the predisposition to growth restriction and special considerations during labor and delivery, is addressed. In addition, we focus on keeping frontline obstetric care providers safe while continuing to provide essential services. Our clinical service model is built around the principles of workplace segregation, responsible social distancing, containment of cross-infection to healthcare providers, judicious use of personal protective equipment, and telemedicine. Our aim is to share a framework that can be adopted by tertiary maternity units managing pregnant women in the flux of a pandemic while maintaining the safety of the patient and healthcare provider at its core.


Assuntos
Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Obstetrícia , Pneumonia Viral/diagnóstico , Pneumonia Viral/tratamento farmacológico , Complicações Infecciosas na Gravidez/virologia , Betacoronavirus , Aleitamento Materno , COVID-19 , Parto Obstétrico , Feminino , Humanos , Transmissão Vertical de Doenças Infecciosas , Pandemias , Equipamento de Proteção Individual , Gravidez , SARS-CoV-2
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA