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1.
Front Cardiovasc Med ; 11: 1345654, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38559673

RESUMO

Extracorporeal membrane oxygenation (ECMO) and extracorporeal life support (ECLS) devices are well-established adjunctive treatment measures for patients with heart failure. ECMO can serve as a bridge to transplant in a chronic setting or as a salvage therapy for patients who are unable to be weaned from bypass following cardiac surgery. However, the role of ECMO as a bridge to definitive therapy in a setting of acute heart failure is less established. Similarly, the treatment of patients using combined ECMO and ECLS devices has been, at times, shown to show some benefit; however, these benefits have not been widely studied. In this study, we present the case of a patient who was diagnosed with severe acute onset heart failure secondary to torrential mitral regurgitation following COVID-19 pneumonia. The patient was emergently placed on venoarterial (VA) ECMO with an indwelling centrifugal pump device in the left ventricle. This combination of ECMO and ECLS served as a bridge to open mitral valve replacement 6 days after presentation. Following successful mitral valve replacement, the patient had persistent right ventricular failure, and therefore, a decision was made to incorporate venovenous (VV) ECMO into the VA ECMO circuit. This technique resulted in a VV-VA or VPa-VA configuration, as oxygenated blood was being returned to the pulmonary artery as well as the descending aorta. VA ECMO was discontinued after 4 days of therapy, and the patient was extubated 3 days later. VV ECMO was weaned over the following week, and the patient was decannulated after a total 23 days of ECMO. The patient was then transitioned to inpatient rehabilitation and ultimately discharged home after 18 days. At the 6-month follow-up, the patient was doing well, and objective cardiopulmonary testing revealed normal function. This case is an excellent demonstration of how advanced ECMO and ECLS devices can be used in unique ways through multiple configurations to rescue and optimize patients in the perioperative period.

2.
Public Health Rep ; : 333549231222479, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38268479

RESUMO

OBJECTIVE: Opioid use disorder (OUD) affects approximately 5.6 million people in the United States annually, yet rates of the use of effective medication for OUD (MOUD) treatment are low. We conducted an observational cohort study from August 2017 through May 2021, the MOUD Study, to better understand treatment engagement and factors that may influence treatment experiences and outcomes. In this article, we describe the study design, data collected, and treatment outcomes. METHODS: We recruited adult patients receiving OUD treatment at US outpatient facilities for the MOUD Study. We collected patient-level data at 5 time points (baseline to 18 months) via self-administered questionnaires and health record data. We collected facility-level data via questionnaires administered to facility directors at 2 time points. Across 16 states, 62 OUD treatment facilities participated, and 1974 patients enrolled in the study. We summarized descriptive data on the characteristics of patients and OUD treatment facilities and selected treatment outcomes. RESULTS: Approximately half of the 62 facilities were private, nonprofit organizations; 62% focused primarily on substance use treatment; and 20% also offered mental health services. Most participants were receiving methadone (61%) or buprenorphine (32%) and were predominately non-Hispanic White (68%), aged 25-44 years (62%), and female (54%). Compared with patient-reported estimates at baseline, 18-month estimates suggested that rates of abstinence increased (55% to 77%), and rates of opioid-related overdoses (7% to 2%), emergency department visits (9% to 4%), and arrests (15% to 7%) decreased. CONCLUSIONS: Our results demonstrated the benefits of treatment retention not only on abstinence from opioid use but also on other quality-of-life metrics, with data collected during an extended period. The MOUD Study produced rich, multilevel data that can lay the foundation for an evidence base to inform OUD treatment and support improvement of care and patient outcomes.

3.
Front Public Health ; 11: 1215925, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38074746

RESUMO

Despite the investment of public resources to fight staggering suicide rates among veterans, we know little about how veterans and service members in crisis communicate suicidal ideations, and what interventions they are willing to receive. We aim to identify communication and suicide intervention preferences of veterans and service members in times of crisis. Descriptive statistics were used to explore veterans communication of suicidal ideations. While 89.9% of participants indicated they were willing to speak to someone when having thoughts of suicide, less than 26% of participants indicated they were willing to bring up their thoughts with a crisis line or veterans organization. Rather, they indicate that family members (62.2%) and military friends (51.1%) would be their primary outreach. Logistic regression was used to determine whether or not preferred interventions varied by participant demographic characteristics. While the majority of participants indicated they were willing to allow intervention (88.6%), no one method was accepted by the majority of the population. The most accepted means of communication was to proactively contact a friend or family member about general life struggles (32.6%) or suicide-specific concerns (27.5%). Many participants were open to receiving resources (42.0%), suicide-specific mental health treatment (36.3%), and some sort of lethal means safety intervention (19.1%-26.4%). The age, marital status, and veterans status of participants significantly impacted what interventions they were willing to allow. We discuss the implications of these findings and the need for evidence-based, multimodal interventions in order to assist veterans in need.


Assuntos
Militares , Suicídio , Veteranos , Humanos , Veteranos/psicologia , Suicídio/psicologia , Ideação Suicida , Violência
4.
Mol Microbiol ; 120(3): 351-383, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37452010

RESUMO

GpsB links peptidoglycan synthases to other proteins that determine the shape of the respiratory pathogen Streptococcus pneumoniae (pneumococcus; Spn) and other low-GC Gram-positive bacteria. GpsB is also required for phosphorylation of proteins by the essential StkP(Spn) Ser/Thr protein kinase. Here we report three classes of frequently arising chromosomal duplications (≈21-176 genes) containing murZ (MurZ-family homolog of MurA) or murA that suppress ΔgpsB or ΔstkP. These duplications arose from three different repeated sequences and demonstrate the facility of pneumococcus to modulate gene dosage of numerous genes. Overproduction of MurZ or MurA alone or overproduction of MurZ caused by ΔkhpAB mutations suppressed ΔgpsB or ΔstkP phenotypes to varying extents. ΔgpsB and ΔstkP were also suppressed by MurZ amino-acid changes distant from the active site, including one in commonly studied laboratory strains, and by truncation or deletion of the homolog of IreB(ReoM). Unlike in other Gram-positive bacteria, MurZ is predominant to MurA in pneumococcal cells. However, ΔgpsB and ΔstkP were not suppressed by ΔclpCP, which did not alter MurZ or MurA amounts. These results support a model in which regulation of MurZ and MurA activity, likely by IreB(Spn), is the only essential requirement for StkP-mediated protein phosphorylation in exponentially growing D39 pneumococcal cells.


Assuntos
Proteínas de Bactérias , Streptococcus pneumoniae , Fosforilação , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Divisão Celular , Mutação
5.
J Genet Couns ; 2023 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-37246362

RESUMO

If passed, the "Access to Genetic Counselor Services Act" will authorize genetic counselors to provide services under Medicare part B. We assert that Medicare policy should be updated through the enactment of this legislation to provide Medicare beneficiaries with direct access to genetic counselor services. In this article, we discuss the background, history, and some recent research relevant to patient access to genetic counselors to provide context and perspective regarding the rationale, justification, and potential results of the proposed legislation. We outline the potential impact of Medicare policy reform, including the effect on access to genetic counselors in high-demand areas or underserved communities. Although the proposed legislation pertains only to Medicare, we argue that private systems will also be impacted by passage as this may lead to an increase in hiring and retention of genetic counselors by health systems, thereby improving access to genetic counselors across the US.

6.
bioRxiv ; 2023 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-37034771

RESUMO

GpsB links peptidoglycan synthases to other proteins that determine the shape of the respiratory pathogen Streptococcus pneumoniae (pneumococcus; Spn ) and other low-GC Gram-positive bacteria. GpsB is also required for phosphorylation of proteins by the essential StkP( Spn ) Ser/Thr protein kinase. Here we report three classes of frequently arising chromosomal duplications (≈21-176 genes) containing murZ (MurZ-family homolog of MurA) or murA that suppress Δ gpsB or Δ stkP . These duplications arose from three different repeated sequences and demonstrate the facility of pneumococcus to modulate gene dosage of numerous genes. Overproduction of MurZ or MurA alone or overexpression of MurZ caused by Δ khpAB mutations suppressed Δ gpsB or Δ stkP phenotypes to varying extents. Δ gpsB and Δ stkP were also suppressed by MurZ amino-acid changes distant from the active site, including one in commonly studied laboratory strains, and by truncation or deletion of the homolog of IreB(ReoM). Unlike in other Gram-positive bacteria, MurZ is predominant to MurA in pneumococcal cells. However, Δ gpsB and Δ stkP were not suppressed by Δ clpCP , which did not alter MurZ or MurA amounts. These results support a model in which regulation of MurZ and MurA activity, likely by IreB( Spn ), is the only essential requirement for protein phosphorylation in exponentially growing D39 pneumococcal cells.

7.
Surg Endosc ; 37(5): 3911-3920, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36729232

RESUMO

BACKGROUND: Emergency colorectal resections carry a higher morbidity and mortality than elective surgery. The use of minimally invasive surgery has now become widespread in elective colorectal surgery, with improved patient outcomes. Laparoscopy is being increasingly used for emergency colorectal resections, but its role is still being defined. Our aim was to observe the uptake of laparoscopy for emergency colorectal surgery in our centre. METHOD: A retrospective single-centre cohort study was performed using local National Emergency Laparotomy Audit data from January 2014-December 2020. All patients who had a colorectal resection were included. Trends in the number and type of resections were recorded. Primary outcome was the proportion of cases started and completed laparoscopically. Secondary outcomes included rate of conversion to open, length of stay and 30-day mortality. RESULTS: A total 523 colorectal resections were performed. The number of cases attempted and completed laparoscopically steadily increased over the study period (28.3% to 63.3% and 16.3% to 35.4%, respectively). The mean rate of conversion to open was 43.8%. The greatest expansion in laparoscopy was for cases of intestinal obstruction, perforation and peritonitis, and for those undergoing Hartmann's procedure and right hemicolectomy. 30­day mortality for cases completed laparoscopically was much lower than those converted or started with open surgery (2.1% vs 11.7% and 17.5%, respectively). Laparoscopic approach was independently associated with reduced length of stay. CONCLUSION: Laparoscopy has been successfully adopted for emergency colorectal resections in our centre, with half of cases felt to be suitable for minimally invasive surgery.


Assuntos
Neoplasias Colorretais , Cirurgia Colorretal , Laparoscopia , Humanos , Estudos Retrospectivos , Estudos de Coortes , Colectomia/métodos , Laparoscopia/métodos , Neoplasias Colorretais/cirurgia , Resultado do Tratamento , Tempo de Internação , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia
8.
J Bacteriol ; 204(11): e0019622, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36286514

RESUMO

Streptococcus pneumoniae (pneumococcus) is an important human pathogen that primarily resides in the nasopharynx. To persist in this polymicrobial environment, pneumococcus must compete with other members of the bacterial community. Competition is mediated in part by the action of the blp locus, which encodes a variable array of bacteriocins and their associated immunity proteins. The locus is controlled by a two-component regulatory system that senses the extracellular concentration of the peptide pheromone, BlpC. There are four major pherotypes of BlpC that can be found in most pneumococcal genomes. Here, we show that the protease SepM is required for activation of three of the four major pherotypes. The only SepM-independent BlpC type is 9 amino acids shorter than the SepM-dependent peptides, consistent with a cleavage event at the C-terminal end. The processing event occurs following secretion, and removal of the C-terminal region is required for binding to the histidine kinase receptor. Synthetic truncated peptides or full-length peptides preincubated with SepM-expressing bacteria can upregulate the blp locus independent of SepM. We show that naturally secreted SepM-independent peptides accumulate in the supernatant of secreting cells at low levels, suggesting a role for the tail in peptide secretion, stability, or solubility and demonstrating a significant trade-off for SepM-independence. IMPORTANCE Streptococcus pneumoniae is an important cause of disease in humans that occurs when the bacteria in the nasopharynx bypasses host defenses to invade deeper tissues. Colonization fitness thus represents an important initial step in pathogenesis. S. pneumoniae produces antimicrobial peptides called bacteriocins that provide a competitive advantage over neighboring bacteria in the nasopharynx. The blp locus encodes a variable array of bacteriocins that participate in competition. Here, we demonstrate that activation of the blp locus requires a surface protease that activates the blp signal peptide. There are naturally occurring signal peptides that do not require cleavage, but these are characterized by poor secretion. We describe an additional, previously unappreciated activation step in the control of bacteriocin production in S. pneumoniae.


Assuntos
Bacteriocinas , Streptococcus pneumoniae , Humanos , Streptococcus pneumoniae/metabolismo , Peptídeo Hidrolases/genética , Peptídeo Hidrolases/metabolismo , Regulação Bacteriana da Expressão Gênica , Bacteriocinas/metabolismo , Endopeptidases/metabolismo , Peptídeos/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo
9.
New Dir Stud Leadersh ; 2022(173): 139-147, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35478339

RESUMO

Science, Technology, Engineering and Mathematics (STEM) disciplines recognize the need for leadership development, but the lack of a professionally endorsed model has led to a patchwork of programmes across the nation, each with its unique brand of skills development. Leadership programmes in six diverse STEM fields are included.


Assuntos
Liderança , Ciência , Engenharia , Humanos , Matemática , Tecnologia
10.
Sci Total Environ ; 828: 154425, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35276136

RESUMO

Forest regeneration has increased in many tropical abandoned lands and current restoration commitments in this region aim to restore over 1,400,000 km2 of degraded land by 2030. Although regenerating forests recover biomass, biodiversity, and processes with time, the recovery trajectories may be uncertain due to past disturbances. Currently, there is a lack of knowledge to sustain the effectiveness of passive regeneration for the recovery of riparian forests and the adjacent waterbodies in the tropics, which may compromise the outcomes of ongoing and future tropical riparian restoration programs. We evaluated the drivers of riparian forest structural recovery and how this relates to stream conditions in 12 abandoned pasturelands in eastern Brazilian Amazonia. These pasturelands range across regeneration age (pasture (PA) - 0 to 4 years; young regeneration (YR) - 8 to 12 years; old regeneration (OR) - 18 to 22 years) and years of past land-use (PA - 23.25 average years of past land-use, YR - 18.25, OR - 7). We compared the conditions of these sites to 4 reference sites with conserved forests (REF, >100 years), where there was no recorded pasture use in the past. Short-term responses of forests and streams to passive regeneration indicated high ecosystem resilience after low to intermediate past land-use intensity, reflected in the improvement of stream ecosystems. Such high resilience is possibly attributable to low- to intermediate-intensity pasture-related disturbances, remaining forest matrix, and residual structures (e.g. roots, sprouts, and in-stream wood) observed in the area. Our results suggest a recovery by 12 to 20 years for riparian forests of this region. However, areas degraded by intensive land-use apparently showed delayed recovery. We conclude that seizing resilience windows (defined here as the period when ecosystems retain high potential resilience) is essential to foster passive recovery of riparian forests and streams more cost-effectively in the tropics.


Assuntos
Ecossistema , Água , Biodiversidade , Florestas , Rios , Árvores
11.
Jt Comm J Qual Patient Saf ; 47(8): 469-480, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34330409

RESUMO

BACKGROUND: The United States is in the midst of an opioid epidemic within the COVID-19 pandemic, and veterans are twice as likely to die from accidental overdose compared to non-veterans. This article describes the Veterans Health Administration (VHA) Rapid Naloxone Initiative, which aims to prevent opioid overdose deaths among veterans through (1) opioid overdose education and naloxone distribution (OEND) to VHA patients at risk for opioid overdose, (2) VA Police naloxone, and (3) select automated external defibrillator (AED) cabinet naloxone. METHODS: VHA has taken a multifaceted, theory-based approach to ensuring the rapid availability of naloxone to prevent opioid overdose deaths. Strategies targeted at multiple levels (for example, patient, provider, health care system) have enabled synergies to speed diffusion of this lifesaving practice. RESULTS: As of April 2021, 285,279 VHA patients had received naloxone from 31,730 unique prescribers, with 1,880 reported opioid overdose reversals with naloxone; 129 VHA facilities had equipped 3,552 VA Police officers with naloxone, with 136 reported opioid overdose reversals with VA Police naloxone; and 77 VHA facilities had equipped 1,095 AED cabinets with naloxone, with 10 reported opioid overdose reversals with AED cabinet naloxone. Remarkably, the COVID-19 pandemic had minimal impact on naloxone dispensing to VHA patients. CONCLUSION: The VHA Rapid Naloxone Initiative saves lives. VHA is sharing many of the tools and resources it has developed to support uptake across other health care systems. Health care systems need to work together to combat this horrific epidemic within a pandemic and prevent a leading cause of accidental death (opioid overdose).


Assuntos
COVID-19 , Overdose de Drogas , Overdose de Drogas/tratamento farmacológico , Overdose de Drogas/prevenção & controle , Humanos , Naloxona/uso terapêutico , Pandemias , SARS-CoV-2 , Estados Unidos , United States Department of Veterans Affairs , Saúde dos Veteranos
12.
Genet Med ; 23(4): 758-766, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33281187

RESUMO

PURPOSE: To estimate health and economic outcomes associated with newborn screening (NBS) for infantile-onset Pompe disease in the United States. METHODS: A decision analytic microsimulation model simulated health and economic outcomes of a birth cohort of 4 million children in the United States. Universal NBS and treatment was compared with clinical identification and treatment of infantile-onset Pompe disease. Main outcomes were projected cases identified, costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) over the life course. RESULTS: Universal NBS for Pompe disease and confirmatory testing was estimated to cost an additional $26 million annually. Additional medication costs associated with earlier treatment initiation were $181 million; however, $8 million in medical care costs for other services were averted due to delayed disease progression. Infants with screened and treated infantile-onset Pompe disease experienced an average lifetime increase of 11.66 QALYs compared with clinical detection. The ICER was $379,000/QALY from a societal perspective and $408,000/QALY from the health-care perspective. Results were sensitive to the cost of enzyme replacement therapy. CONCLUSION: Newborn screening for Pompe disease results in substantial health gains for individuals with infantile-onset Pompe disease, but with additional costs.


Assuntos
Doença de Depósito de Glicogênio Tipo II , Criança , Análise Custo-Benefício , Terapia de Reposição de Enzimas , Doença de Depósito de Glicogênio Tipo II/diagnóstico , Doença de Depósito de Glicogênio Tipo II/epidemiologia , Doença de Depósito de Glicogênio Tipo II/genética , Humanos , Lactente , Recém-Nascido , Triagem Neonatal , Anos de Vida Ajustados por Qualidade de Vida , Estados Unidos/epidemiologia
14.
Schizophr Bull ; 47(2): 309-322, 2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-32989443

RESUMO

BACKGROUND AND OBJECTIVE: Experiencing psychosis can be associated with changes in how people see themselves as individuals and in relation to others (ie, changes in their identity). However, identity changes receive little attention in treatment, possibly due to a lack of clarity or consensus around what identity change means in people with psychosis. We aimed to create a conceptual framework synthesizing how identity changes are understood in the psychosis literature. METHODS: Electronic databases were searched up to April 2020. Studies about identity changes among people with psychotic disorders were analyzed using narrative synthesis by a collaborative review team, including researchers from different disciplines, clinicians, and people who have experienced psychosis. RESULTS: Of 10 389 studies screened, 59 were eligible. Identity changes are understood in 5 ways as (1) characteristics of psychosis, (2) consequences of altered cognitive functioning, (3) consequences of internalized stigma, (4) consequences of lost roles and relationships, and (5) reflections of personal growth. These 5 understandings are not mutually exclusive. Across a heterogeneous literature, identity changes were mostly framed in terms of loss. CONCLUSIONS: Our conceptual framework, comprising 5 understandings, highlights the complexity of studying identity changes and suggests important implications for practice and research. For clinicians, this framework can inform new therapeutic approaches where the experience and impact of identity changes are acknowledged and addressed as part of treatment. For researchers, the conceptual framework offers a way of locating their understandings of identity changes when undertaking research in this area.


Assuntos
Disfunção Cognitiva/fisiopatologia , Transtornos Psicóticos/fisiopatologia , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Autoimagem , Estigma Social , Disfunção Cognitiva/etiologia , Humanos , Transtornos Psicóticos/complicações
15.
Aust N Z J Psychiatry ; 55(7): 666-677, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33176436

RESUMO

OBJECTIVES: To profile the long-term mental health outcomes of those affected by the 2009 Black Saturday bushfires and to document the course of mental health since the disaster. METHOD: The longitudinal Beyond Bushfires study included 1017 respondents (Wave 1; 3-4 years after the fires), 736 (76.1%) at Wave 2 (5 years after the fires) and 525 (51.6%) at Wave 3 (10 years after the fires). The survey indexed fire-related and subsequent stressful events, probable posttraumatic stress disorder, major depressive disorder, alcohol use, severe distress and receipt of health services for mental health problems. RESULTS: Relative to their status 3-4 years after the fires, there were reduced rates of fire-related posttraumatic stress disorder (6.2% vs 12.2%), general posttraumatic stress disorder (14.9% vs 18.7%) and severe distress (4.4% vs 7.5%) at 10 years. There were comparable rates between Wave 1 and Wave 3 for depression (10.9% vs 8.3%) and alcohol abuse (21.8% vs 18.5%). Of people in high-affected regions, 22.1% had posttraumatic stress disorder, depression or severe distress at Wave 3. One-third to one-half of participants who reported probable posttraumatic stress disorder or depression at any assessment did not display the disorder at the next assessment. Worsening of mental health at Wave 3 was associated with the extent of property loss, exposure to recent traumatic events or recent stressful life events. Only 24.6% of those with a probable disorder had sought professional help for this in the previous 6 months. CONCLUSION: Approximately one-fifth of people from high-affected areas have a probable psychological disorder a decade after the fires. Mental health appears to fluctuate for those who are not consistently resilient, apparently as a result of ongoing stressors. The observation that most people with probable disorder are not receiving care highlights the need for further planning about managing long-term mental health needs of disaster-affected communities.


Assuntos
Transtorno Depressivo Maior , Desastres , Incêndios , Transtornos de Estresse Pós-Traumáticos , Transtorno Depressivo Maior/epidemiologia , Humanos , Saúde Mental , Transtornos de Estresse Pós-Traumáticos/epidemiologia
17.
J Bacteriol ; 202(18)2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32601068

RESUMO

Posttranscriptional gene regulation often involves RNA-binding proteins that modulate mRNA translation and/or stability either directly through protein-RNA interactions or indirectly by facilitating the annealing of small regulatory RNAs (sRNAs). The human pathogen Streptococcus pneumoniae D39 (pneumococcus) does not encode homologs to RNA-binding proteins known to be involved in promoting sRNA stability and function, such as Hfq or ProQ, even though it contains genes for at least 112 sRNAs. However, the pneumococcal genome contains genes for other RNA-binding proteins, including at least six S1 domain proteins: ribosomal protein S1 (rpsA), polynucleotide phosphorylase (pnpA), RNase R (rnr), and three proteins with unknown functions. Here, we characterize the function of one of these conserved, yet uncharacterized, S1 domain proteins, SPD_1366, which we have renamed CvfD (conserved virulence factor D), since loss of the protein results in attenuation of virulence in a murine pneumonia model. We report that deletion of cvfD impacts the expression of 144 transcripts, including the pst1 operon, encoding phosphate transport system 1 in S. pneumoniae We further show that CvfD posttranscriptionally regulates the PhoU2 master regulator of the pneumococcal dual-phosphate transport system by binding phoU2 mRNA and impacting PhoU2 translation. CvfD not only controls expression of phosphate transporter genes but also functions as a pleiotropic regulator that impacts cold sensitivity and the expression of sRNAs and genes involved in diverse cellular functions, including manganese uptake and zinc efflux. Together, our data show that CvfD exerts a broad impact on pneumococcal physiology and virulence, partly by posttranscriptional gene regulation.IMPORTANCE Recent advances have led to the identification of numerous sRNAs in the major human respiratory pathogen S. pneumoniae However, little is known about the functions of most sRNAs or RNA-binding proteins involved in RNA biology in pneumococcus. In this paper, we characterize the phenotypes and one target of the S1 domain RNA-binding protein CvfD, a homolog of general stress protein 13 identified, but not extensively characterized, in other Firmicutes species. Pneumococcal CvfD is a broadly pleiotropic regulator, whose absence results in misregulation of divalent cation homeostasis, reduced translation of the PhoU2 master regulator of phosphate uptake, altered metabolism and sRNA amounts, cold sensitivity, and attenuation of virulence. These findings underscore the critical roles of RNA biology in pneumococcal physiology and virulence.


Assuntos
Proteínas de Bactérias/metabolismo , Resposta ao Choque Frio , Fosfatos/metabolismo , Proteínas de Ligação a RNA/metabolismo , Streptococcus pneumoniae/metabolismo , Fatores de Virulência/metabolismo , Animais , Modelos Animais de Doenças , Regulação Bacteriana da Expressão Gênica , Masculino , Camundongos , Camundongos Endogâmicos ICR , Infecções Pneumocócicas/microbiologia , Proteínas Ribossômicas/metabolismo , Streptococcus pneumoniae/patogenicidade , Virulência
18.
J Surg Case Rep ; 2020(4): rjaa083, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32377333

RESUMO

Visceral arteriovenous malformations (AVMs) are extremely rare with only a few cases described within the literature. To date, no cases of ischaemic colitis related to arteriovenous malformations affecting both superior and inferior mesenteric arteries have been reported. We report the first case of acute ischaemic colitis caused by venous congestion and reduced arterial flow due to combined AVMs in the territory of superior and inferior mesenteric arteries in a 51-year-old patient. After a multidisciplinary meeting, interventional radiology embolization was considered to be of unlikely benefit due to extensive varicosities; therefore, surgical treatment in the form of open subtotal colectomy and end ileostomy was performed. This case report demonstrates the severity and the complexity in the management of AVM-related ischaemic colitis, together with a review of the literature.

19.
BJPsych Open ; 6(1): e1, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31796146

RESUMO

BACKGROUND: Disasters pose a documented risk to mental health, with a range of peri- and post-disaster factors (both pre-existing and disaster-precipitated) linked to adverse outcomes. Among these, increasing empirical attention is being paid to the relation between disasters and violence. AIMS: This study examined self-reported experiences of assault or violence victimisation among communities affected by high, medium, and low disaster severity following the 2009 bushfires in Victoria, Australia. The association between violence, mental health outcomes and alcohol misuse was also investigated. METHOD: Participants were 1016 adults from high-, medium- and low-affected communities, 3-4 years after an Australian bushfire disaster. Rates of reported violence were compared by areas of bushfire-affectedness. Logistic regression models were applied separately to men and women to assess the experience of violence in predicting general and fire-related post-traumatic stress disorder, depression and alcohol misuse. RESULTS: Reports of experiencing violence were significantly higher among high bushfire-affected compared with low bushfire-affected regions. Analyses indicated the significant relationship between disaster-affectedness and violence was observed for women only, with rates of 1.0, 0 and 7.4% in low, medium and high bushfire-affected areas, respectively. Among women living in high bushfire-affected areas, negative change to income was associated with an increased likelihood of experiencing violence (odds ratio, 4.68). For women, post-disaster violence was associated with more severe post-traumatic stress disorder and depression symptoms. CONCLUSIONS: Women residing within high bushfire-affected communities experienced the highest levels of violence. These post-disaster experiences of violence are associated with post-disaster changes to income and with post-traumatic stress disorder and depression symptoms among women. These findings have critical implications for the assessment of, and interventions for, women experiencing or at risk of violence post-disaster.

20.
Sci Total Environ ; 692: 1291-1303, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31539961

RESUMO

Pesticides are important contributors to the global freshwater biodiversity crisis. Among pesticides, neonicotinoids are the best-selling class of agricultural insecticides and are suspected to represent significant risks to freshwater and terrestrial ecosystems worldwide. Despite growing recognition that neonicotinoid impacts may be modified by the presence of additional stressors, there is limited information about their interactions with other agricultural stressors in freshwater ecosystems. We conducted an outdoor pond-mesocosm experiment to investigate the individual and interactive effects of nutrients, fine sediment, and imidacloprid (a neonicotinoid insecticide) inputs on freshwater community structure (density, diversity, and composition of zooplankton and benthic invertebrates) and ecosystem functioning (ecosystem metabolism, primary production, and organic matter decomposition). We hypothesized antagonistic nutrient-imidacloprid, and synergistic sediment-imidacloprid interactions, affecting aquatic invertebrate communities. The three stressors had significant individual and interactive effects on pond ecosystems. The insecticide neutralized the positive effects of nutrient additions on benthic invertebrate richness and mitigated the negative effects of sediment on zooplankton communities (antagonistic interactions). Moreover, we observed compensatory responses of tolerant benthic invertebrates, which resulted in reversal interactions between sediment and imidacloprid. Furthermore, our observations suggest that imidacloprid has the potential to increase net ecosystem production at environmentally relevant concentrations. Our findings support the hypothesis that the impacts of imidacloprid may be modified by other agricultural stressors. This has important implications on a global scale, given the widespread use of these pesticides in intensive agricultural landscapes and the growing body of literature suggesting that traditional pesticide assessment frameworks, based on laboratory toxicity tests alone, may be insufficient to adequately predict effects to complex freshwater ecosystems.


Assuntos
Organismos Aquáticos/fisiologia , Ecossistema , Inseticidas/toxicidade , Neonicotinoides/toxicidade , Poluentes Químicos da Água/toxicidade , Agricultura , Animais , Biodiversidade , Monitoramento Ambiental , Água Doce , Inseticidas/análise , Invertebrados/fisiologia , Neonicotinoides/análise , Nitrogênio , Fósforo , Poluentes Químicos da Água/análise , Zooplâncton
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