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1.
Front Public Health ; 11: 1283113, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38106901

RESUMO

Introduction: The Eidolon helvum fruit bat is one of the most widely distributed fruit bats in Africa and known to be a reservoir for several pathogenic viruses that can cause disease in animals and humans. To assess the risk of zoonotic spillover, we conducted a serological survey of 304 serum samples from E. helvum bats that were captured for human consumption in Makurdi, Nigeria. Methods: Using pseudotyped viruses, we screened 304 serum samples for neutralizing antibodies against viruses from the Coronaviridae, Filoviridae, Orthomyxoviridae and Paramyxoviridae families. Results: We report the presence of neutralizing antibodies against henipavirus lineage GH-M74a virus (odds ratio 6.23; p < 0.001), Nipah virus (odds ratio 4.04; p = 0.00031), bat influenza H17N10 virus (odds ratio 7.25; p < 0.001) and no significant association with Ebola virus (odds ratio 0.56; p = 0.375) in this bat cohort. Conclusion: The data suggest a potential risk of zoonotic spillover including the possible circulation of highly pathogenic viruses in E. helvum populations. These findings highlight the importance of maintaining sero-surveillance of E. helvum, and the necessity for further, more comprehensive investigations to monitor changes in virus prevalence, distribution over time, and across different geographic locations.


Assuntos
Quirópteros , Viroses , Animais , Humanos , Nigéria/epidemiologia , Zoonoses/epidemiologia , Anticorpos Neutralizantes
2.
Front Immunol ; 14: 1184362, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37790941

RESUMO

Background: The virus neutralization assay is a principal method to assess the efficacy of antibodies in blocking viral entry. Due to biosafety handling requirements of viruses classified as hazard group 3 or 4, pseudotyped viruses can be used as a safer alternative. However, it is often queried how well the results derived from pseudotyped viruses correlate with authentic virus. This systematic review and meta-analysis was designed to comprehensively evaluate the correlation between the two assays. Methods: Using PubMed and Google Scholar, reports that incorporated neutralisation assays with both pseudotyped virus, authentic virus, and the application of a mathematical formula to assess the relationship between the results, were selected for review. Our searches identified 67 reports, of which 22 underwent a three-level meta-analysis. Results: The three-level meta-analysis revealed a high level of correlation between pseudotyped viruses and authentic viruses when used in an neutralisation assay. Reports that were not included in the meta-analysis also showed a high degree of correlation, with the exception of lentiviral-based pseudotyped Ebola viruses. Conclusion: Pseudotyped viruses identified in this report can be used as a surrogate for authentic virus, though care must be taken in considering which pseudotype core to use when generating new uncharacterised pseudotyped viruses.


Assuntos
Ebolavirus , Pseudotipagem Viral
3.
J Urol ; 210(6): 865-873, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37651378

RESUMO

PURPOSE: Patients may remain catheterized after artificial urinary sphincter surgery to prevent urinary retention, despite a lack of evidence to support this practice. Our study aims to evaluate the feasibility of outpatient, catheter-free continence surgery using a multi-institutional database. We hypothesize that between catheterized controls and patients without a catheter, there would be no difference in the rate of urinary retention or postoperative complications. MATERIALS AND METHODS: We conducted a retrospective review of patients undergoing first-time artificial urinary sphincter placement from 2009-2021. Patients were stratified by postoperative catheter status into either no-catheter (leaving the procedure without a catheter) or catheter (postoperative indwelling catheter for ∼24 hours). The primary outcome, urinary retention, was defined as catheterization due to subjective voiding difficulty or documented postvoid residual over 250 mL. RESULTS: Our study identified 302 catheter and 123 no-catheter patients. Twenty (6.6%) catheter and 9 (7.3%) no-catheter patients developed urinary retention (P = .8). On multivariable analysis, controlling for age, cuff size, radiation history and surgeon, there was no statistically significant association between omitting a catheter and urinary retention (OR: 0.45, 95% CI: 0.13-1.58; P = .2). Furthermore, at 30 months follow-up, Kaplan-Meier survival analysis revealed that device survival was 70% (95% CI: 62%-76%) vs 69% (95% CI: 48%-82%) for the catheter and no-catheter group, respectively. CONCLUSIONS: In our multi-institutional cohort, overall retention rates were low (7%) in groups with a catheter and without. Obviating postoperative catheterization facilitates outpatient incontinence surgery without altering reoperation over medium-term follow-up.


Assuntos
Incontinência Urinária , Retenção Urinária , Humanos , Retenção Urinária/etiologia , Retenção Urinária/prevenção & controle , Estudos Retrospectivos , Incontinência Urinária/etiologia , Micção , Bexiga Urinária/cirurgia
4.
J Biol Chem ; 299(6): 104756, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37116705

RESUMO

Phosphatidylserine (PS) synthase from Candida albicans, encoded by the CHO1 gene, has been identified as a potential drug target for new antifungals against systemic candidiasis. Rational drug design or small molecule screening are effective ways to identify specific inhibitors of Cho1, but both will be facilitated by protein purification. Due to the transmembrane nature of Cho1, methods were needed to solubilize and purify the native form of Cho1. Here, we used six non-ionic detergents and three styrene maleic acids (SMAs) to solubilize an HA-tagged Cho1 protein from the total microsomal fractions. Blue native PAGE and immunoblot analysis revealed a single band corresponding to Cho1 in all detergent-solubilized fractions, while two bands were present in the SMA2000-solubilized fraction. Our enzymatic assay suggests that digitonin- or DDM-solubilized enzyme has the most PS synthase activity. Pull-downs of HA-tagged Cho1 from the digitonin-solubilized fraction reveal an apparent MW of Cho1 consistent with a hexamer. Furthermore, negative-staining electron microscopy analysis and AlphaFold2 structure prediction modeling suggest the hexamer is composed of a trimer of dimers. We purified Cho1 protein to near-homogeneity as a hexamer using affinity chromatography and TEV protease treatment, and optimized Cho1 enzyme activity for manganese and detergent concentrations, temperature (24 °C), and pH (8.0). The purified Cho1 has a Km for its substrate CDP-diacylglycerol of 72.20 µM with a Vmax of 0.079 nmol/(µg∗min) while exhibiting a sigmoidal kinetic curve for its other substrate serine, indicating cooperative binding. Purified hexameric Cho1 can potentially be used in downstream structure determination and small drug screening.


Assuntos
CDPdiacilglicerol-Serina O-Fosfatidiltransferase , Candida albicans , Candida albicans/enzimologia , CDPdiacilglicerol-Serina O-Fosfatidiltransferase/química , Detergentes/farmacologia , Digitonina/metabolismo
5.
Crit Criminol ; 31(1): 127-144, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37051417

RESUMO

This paper hosts the first meaningful dialogue between two important epistemic movements for criminology: zemiology and decolonisation. I identify that zemiology has a disciplinary blindness to colonialism and explain this using Gurminder K. Bhambra's scholarship-and cognate scholarship-as a frame. Three cases-Pemberton's Harmful Societies, Grenfell, and Border Zemiology-are selected for their critical importance within zemiology. They are used to argue that zemiology works within a standard narrative of modernity characterised by capitalist nation-states, which does not recognise the colonial foundations of both of these. Capitalist modernity is, however, a colonial formation. Recognising this allows for a better understanding for a wide range of harms. I then discuss future directions for decolonial zemiology, advocating not for expansion of repertoire, but canonical revision so that colonialism is afforded space as an explanatory frame and zemiology can better explain social harm on a global level.

6.
J Appl Microbiol ; 134(2)2023 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-36724296

RESUMO

AIMS: Filoviruses encompass highly pathogenic viruses placing significant public health burden on countries affected. Efforts for improved diagnostics and surveillance are needed. The requirement for high-containment can be circumvented by using pseudotype viruses (PV), which can be handled safely, in tropism, drug screening, vaccine evaluation, and serosurveillance studies. We assessed the stability and functionality after long-term storage of lyophilised filovirus pseudotypes for use in neutralisation assays. METHODS AND RESULTS: We generated a panel of filovirus lentiviral pseudotypes followed by lyophilisation and storage in different conditions. Next, we reconstituted and tested PVs in infection experiments and pseudotype neutralisation assays where possible. Lyophilised Ebola and Marburg PVs retained production titres for at least two years when stored at +4˚C or less. Lyophilised Ebola PVs performed similarly to non-lyophilised PVs in neutralisation assays after reconstitution. When stored at high temperatures (+37˚C), lyophilised PVs did not retain titres after 1-month storage, however, when lyophilised using pilot-scale facilities EBOV PVs retained titres and performed as standard in neutralisation assays after on 1-month storage at 37˚C. CONCLUSIONS: Filovirus PVs are amenable to lyophilisation and can be stored for at least 2 years in a household fridge to be used in antibody assays. Lyophilisation performed in the right conditions would allow transportation at room temperature, even in warmer climates.


Assuntos
Ebolavirus , Filoviridae , Doença pelo Vírus Ebola , Vírus , Humanos , Testes de Neutralização/métodos , Doença pelo Vírus Ebola/prevenção & controle , Anticorpos Antivirais
7.
Molecules ; 28(2)2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36677538

RESUMO

Broadly neutralizing antibodies (bNAbs) are potent in neutralizing a wide range of HIV strains. VRC01 is a CD4-binding-site (CD4-bs) class of bNAbs that binds to the conserved CD4-binding region of HIV-1 envelope (env) protein. Natural products that mimic VRC01 bNAbs by interacting with the conserved CD4-binding regions may serve as a new generation of HIV-1 entry inhibitors by being broadly reactive and potently neutralizing. This study aimed to identify compounds that mimic VRC01 by interacting with the CD4-bs of HIV-1 gp120 and thereby inhibiting viral entry into target cells. Libraries of purchasable natural products were virtually screened against clade A/E recombinant 93TH057 (PDB: 3NGB) and clade B (PDB ID: 3J70) HIV-1 env protein. Protein-ligand interaction profiling from molecular docking and dynamics simulations showed that the compounds had intermolecular hydrogen and hydrophobic interactions with conserved amino acid residues on the CD4-binding site of recombinant clade A/E and clade B HIV-1 gp120. Four potential lead compounds, NP-005114, NP-008297, NP-007422, and NP-007382, were used for cell-based antiviral infectivity inhibition assay using clade B (HXB2) env pseudotype virus (PV). The four compounds inhibited the entry of HIV HXB2 pseudotype viruses into target cells at 50% inhibitory concentrations (IC50) of 15.2 µM (9.7 µg/mL), 10.1 µM (7.5 µg/mL), 16.2 µM (12.7 µg/mL), and 21.6 µM (12.9 µg/mL), respectively. The interaction of these compounds with critical residues of the CD4-binding site of more than one clade of HIV gp120 and inhibition of HIV-1 entry into the target cell demonstrate the possibility of a new class of HIV entry inhibitors.


Assuntos
Produtos Biológicos , Anticorpos Amplamente Neutralizantes , HIV-1 , Humanos , Antígenos CD4/metabolismo , Anticorpos Anti-HIV , Proteína gp120 do Envelope de HIV , Infecções por HIV , HIV-1/efeitos dos fármacos , Simulação de Acoplamento Molecular , Produtos Biológicos/farmacologia
8.
Viruses ; 14(12)2022 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-36560754

RESUMO

Rabies is a neglected tropical disease. The prototype virus, the rabies virus, still causes tens of thousands of human fatalities annually. Rabies is one member of the genus Lyssavirus. The burden of other lyssaviruses is unclear. The continued emergence of novel lyssaviruses means that assessment of vaccine efficacy against these viruses is critical, as standard rabies vaccines are not efficacious against all lyssaviruses. Taiwan bat lyssavirus (TWBLV) was first reported in 2018 following isolation from Japanese house bats. Since the initial detection and genetic characterisation, no attempts have been made to antigenically define this virus. Due to the inaccessibility of the wildtype isolate, the successful generation of a live recombinant virus, cSN-TWBLV, is described, where the full-length genome clone of the RABV vaccine strain, SAD-B19, was constructed with the glycoprotein of TWBLV. In vitro and in vivo characterization of cSN-TWBLV was undertaken and demonstrated evidence for cross-neutralisation of cSN-TWBLV with phylogroup I -specific sera and rabies virus standard sera. For neutralisation equivalent to 0.5 IU/mL of WHO and World Organisation of Animal Health (WOAH) sera against CVS, 0.5 IU/mL of WOAH sera and 2.5 IU/mL of WHO sera were required to neutralise cSN-TWBLV. In addition, specific sera for ARAV and EBLV-1 exhibited the highest neutralising antibody titres against cSN-TWBLV, compared to other phylogroup I-specific sera.


Assuntos
Quirópteros , Lyssavirus , Vacina Antirrábica , Vírus da Raiva , Raiva , Infecções por Rhabdoviridae , Animais , Humanos , Raiva/prevenção & controle , Raiva/veterinária , Taiwan , Anticorpos Antivirais , Infecções por Rhabdoviridae/prevenção & controle , Infecções por Rhabdoviridae/veterinária , Vírus da Raiva/genética
9.
Sci Rep ; 12(1): 22330, 2022 12 25.
Artigo em Inglês | MEDLINE | ID: mdl-36567369

RESUMO

Elucidating the adaptive immune characteristics of natural protection to Lassa fever (LF) is vital in designing and selecting optimal vaccine candidates. With rejuvenated interest in LF and a call for accelerated research on the Lassa virus (LASV) vaccine, there is a need to define the correlates of natural protective immune responses to LF. Here, we describe cellular and antibody immune responses present in survivors of LF (N = 370) and their exposed contacts (N = 170) in a LASV endemic region in Nigeria. Interestingly, our data showed comparable T cell and binding antibody responses from both survivors and their contacts, while neutralizing antibody responses were primarily seen in the LF survivors and not their contacts. Neutralizing antibody responses were found to be cross-reactive against all five lineages of LASV with a strong bias to Lineage II, the prevalent strain in southern Nigeria. We demonstrated that both T cell and antibody responses were not detectable in peripheral blood after a decade in LF survivors. Notably LF survivors maintained high levels of detectable binding antibody response for six months while their contacts did not. Lastly, as potential vaccine targets, we identified the regions of the LASV Glycoprotein (GP) and Nucleoprotein (NP) that induced the broadest peptide-specific T cell responses. Taken together this data informs immunological readouts and potential benchmarks for clinical trials evaluating LASV vaccine candidates.


Assuntos
Febre Lassa , Vírus Lassa , Humanos , Nigéria/epidemiologia , Imunidade Celular , Anticorpos Neutralizantes , Sobreviventes
10.
Polymers (Basel) ; 14(19)2022 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-36236120

RESUMO

In this proof-of-concept study, we aim to produce a polyurethane (PU)-based composite that can reduce the amount of viable SARS-CoV-2 virus in contact with the surface of the polymeric film without further interventions such as manual cleaning. Current protocols for maintaining the hygiene of commonly used touchpoints (door handles, light switches, shop counters) typically rely on repeated washing with antimicrobial products. Since the start of the SARS-CoV-2 pandemic, frequent and costly surface sanitization by workers has become standard procedure in many public areas. Therefore, materials that can be retrofitted to touchpoints, yet inhibit pathogen growth for extended time periods are an important target. Herein, we design and synthesise the PU using a one-pot synthetic procedure on a multigram scale from commercial starting materials. The PU forms a robust composite thin film when loaded with 10 wt% silver nanoparticles (AgNPs). The addition of AgNPs increases the ultimate tensile strength, modules of toughness and modulus of elasticity at the cost of a reduced elongation at break when compared to the pristine PU. Comparative biological testing was carried out by the addition of pseudotyped virus (PV) bearing the SARS-CoV-2 beta (B.1.351) VOC spike protein onto the film surfaces of either the pristine PU or the PU nanocomposite. After 24 h without further human intervention the nanocomposite reduced the amount of viable virus by 67% (p = 0.0012) compared to the pristine PU treated under the same conditions. The significance of this reduction in viable virus load caused by our nanocomposite is that PUs form the basis of many commercial paints and coatings. Therefore, we envisage that this work will provide the basis for further progress towards producing a retrofittable surface that can be applied to a wide variety of common touchpoints.

12.
Nat Commun ; 13(1): 1706, 2022 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-35361761

RESUMO

Some filoviruses can be transmitted to humans by zoonotic spillover events from their natural host and filovirus outbreaks have occured with increasing frequency in the last years. The filovirus Lloviu virus (LLOV), was identified in 2002 in Schreiber's bats (Miniopterus schreibersii) in Spain and was subsequently detected in bats in Hungary. Here we isolate infectious LLOV from the blood of a live sampled Schreiber's bat in Hungary. The isolate is subsequently sequenced and cultured in the Miniopterus sp. kidney cell line SuBK12-08. It is furthermore able to infect monkey and human cells, suggesting that LLOV might have spillover potential. A multi-year surveillance of LLOV in bats in Hungary detects LLOV RNA in both deceased and live animals as well as in coupled ectoparasites from the families Nycteribiidae and Ixodidae. This correlates with LLOV seropositivity in sampled Schreiber's bats. Our data support the role of bats, specifically Miniopterus schreibersii as hosts for LLOV in Europe. We suggest that bat-associated parasites might play a role in the natural ecology of filoviruses in temperate climate regions compared to filoviruses in the tropics.


Assuntos
Quirópteros , Dípteros , Filoviridae , Animais , Humanos , Hungria/epidemiologia , Zoonoses
13.
J Gen Virol ; 103(4)2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35377298

RESUMO

Following the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in PR China in late 2019 a number of variants have emerged, with two of these - alpha and delta - subsequently growing to global prevalence. One characteristic of these variants are changes within the spike protein, in particular the receptor-binding domain (RBD). From a public health perspective, these changes have important implications for increased transmissibility and immune escape; however, their presence could also modify the intrinsic host range of the virus. Using viral pseudotyping, we examined whether the variants of concern (VOCs) alpha, beta, gamma and delta have differing host angiotensin-converting enzyme 2 (ACE2) receptor usage patterns, focusing on a range of relevant mammalian ACE2 proteins. All four VOCs were able to overcome a previous restriction for mouse ACE2, with demonstrable differences also seen for individual VOCs with rat, ferret or civet ACE2 receptors, changes that we subsequently attributed to N501Y and E484K substitutions within the spike RBD.


Assuntos
COVID-19 , SARS-CoV-2 , Enzima de Conversão de Angiotensina 2/genética , Animais , Furões , Especificidade de Hospedeiro , Humanos , Camundongos , Peptidil Dipeptidase A/química , Ratos , SARS-CoV-2/genética
14.
Psychol Trauma ; 14(5): 804, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35324230

RESUMO

Reports an error in "The effects of web-prolonged exposure among military personnel and veterans with posttraumatic stress disorder" by Carmen P. McLean, Edna B. Foa, Katherine A. Dondanville, Christopher K. Haddock, Madeleine L. Miller, Sheila A. M. Rauch, Jeffery S. Yarvis, Edward C. Wright, Brittany N. Hall-Clark, Brooke A. Fina, Brett T. Litz, Jim Mintz, Stacey Young-McCaughan and Alan L. Peterson (Psychological Trauma: Theory, Research, Practice, and Policy, 2021[Sep], Vol 13[6], 621-631). In the original article, "for the STRONG STAR Consortium" was missing from the end of the author line. In addition, the numbering and text of the affiliations for Edward C. Wright, Brittany N. Hall-Clark, Brooke A. Fina, Brett T. Litz, Jim Mintz, Stacey Young-McCaughan, and Alan L. Peterson were incorrect because of duplicated affiliation details and associated typographical errors. Finally, in the References, "for the STRONG STAR Consortium" and "on behalf of the STRONG STAR Consortium" were missing from the ends of the author lists for Foa et al. (2018) and Resick et al. (2015), respectively. The online version of this article has been corrected. (The following abstract of the original article appeared in record 2020-86687-001). OBJECTIVE: Web-based treatments address many of the logistical and stigma-related barriers to in-person behavioral health care. Prior studies of web-based treatments for posttraumatic stress disorder (PTSD) did not employ gold-standard treatments and have not compared to in-person therapy. METHOD: We compared a web version of Prolonged Exposure Therapy, "Web-PE," to in-person Present-Centered Therapy (PCT) in a randomized controlled trial (RCT) with 40 military personnel with PTSD seeking treatment at Fort Hood, Texas. Due to recruitment challenges, we terminated the RCT and subsequently examined the effects of Web-PE in an uncontrolled open trial with 34 service members and veterans recruited nationwide. Both studies assessed PTSD, depressive symptoms, and health functioning at baseline and 1 and 3 months posttreatment; the RCT also included a 6-month assessment. RESULTS: Results of the RCT showed no differential impact for Web-PE and PCT, although more PCT participants achieved clinically significant change at one of the follow-up assessments. Both treatment conditions significantly reduced self-reported and blind independent interviewer-assessed symptoms of PTSD. Results of the open trial showed that Web-PE was associated with significant reductions in self-reported PTSD symptoms, with a much larger effect size than in the RCT. CONCLUSIONS: Web-PE significantly reduced PTSD symptoms in both studies, although the reductions in PTSD symptoms were greater among open trial participants, who were specifically seeking a web-based treatment. Future research should evaluate Web-PE relative to another web-based treatment. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Assuntos
Terapia Implosiva , Militares , Trauma Psicológico , Transtornos de Estresse Pós-Traumáticos , Veteranos , Humanos , Terapia Implosiva/métodos , Militares/psicologia , Transtornos de Estresse Pós-Traumáticos/terapia , Resultado do Tratamento
15.
ChemMedChem ; 17(7): e202100641, 2022 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-35191598

RESUMO

The pentafluorosulfanyl (-SF5 ) functional group is of increasing interest as a bioisostere in medicinal chemistry. A library of SF5 -containing compounds, including amide, isoxazole, and oxindole derivatives, was synthesised using a range of solution-based and solventless methods, including microwave and ball-mill techniques. The library was tested against targets including human dihydroorotate dehydrogenase (HDHODH). A subsequent focused approach led to synthesis of analogues of the clinically used disease modifying anti-rheumatic drugs (DMARDs), Teriflunomide and Leflunomide, considered for potential COVID-19 use, where SF5 bioisostere deployment led to improved inhibition of HDHODH compared with the parent drugs. The results demonstrate the utility of the SF5 group in medicinal chemistry.


Assuntos
Química Farmacêutica , Di-Hidro-Orotato Desidrogenase , Amidas , Di-Hidro-Orotato Desidrogenase/antagonistas & inibidores , Humanos
16.
Psychol Trauma ; 2022 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-35099219

RESUMO

OBJECTIVE: Web-based prolonged exposure therapy (Web-PE) has potential to increase the reach of effective posttraumatic stress disorder (PTSD) treatment. While there is initial support for the efficacy of Web-PE, no studies have examined the perceptions and experiences of participants receiving PE in this novel, Web based format. METHOD: We used a mixed-methods convergent design to examine and integrate quantitative and qualitative data of participant perceptions and experiences of Web-PE. Treatment-seeking active duty military personnel or veterans (N = 29) who received Web-PE completed posttreatment surveys about perceptions of Web-PE and a brief qualitative interview. Thematic coding was used to identify qualitative themes, which were integrated with quantitative data in a joint display. RESULTS: Although many were initially skeptical of experiencing benefit, participants reported that Web-PE was helpful. They appreciated the flexibility of online therapy and reported that self-motivation was important for engagement. Web-PE therapists were well-regarded, although additional therapist support and technical improvements to the Web-PE program were suggested. Scores on the perceptions of Web-PE survey, PTSD survey, and other quantitative data corroborated the qualitative themes. CONCLUSION: Perceptions and experience of Web-PE are favorable and help to highlight the strengths (e.g., flexibility) and challenges (e.g., requiring self-motivation) associated with Web-treatment for PTSD. The results of this study may inform further development of Web-PE or other Web-based treatment programs. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

17.
J Urol ; 207(6): 1268-1275, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35050698

RESUMO

PURPOSE: In order to accurately characterize how a history of radiation therapy affects the lifespan of replacement artificial urinary sphincters (AUSs), all possible sources of device failure must be considered. We assessed the competing risks of device failure based on radiation history in men with replacement AUSs. MATERIALS AND METHODS: We identified men who had a replacement AUS in a single institutional, retrospective database. To assess survival from all-cause device failure based on radiation history and other factors, we conducted Kaplan-Meier, Cox proportional-hazards and competing risks analyses. RESULTS: Among 247 men who had a first replacement AUS, men with a history of radiation had shorter time to all-cause device failure (median 1.4 vs 3.5 years for men with radiation vs without radiation history, p=0.02). On multivariable Cox-proportional hazards analysis, previous radiation was associated with increased risk of all-cause device failure (HR: 2.12, 95% CI: 1.30-3.43, p=0.002). On multivariable cause-specific hazards analysis, prior radiation was associated with a higher risk of erosion/infection (HR: 7.57, 95% CI: 2.27-25.2, p <0.001), but was not associated with risk of urethral atrophy (p=0.5) or mechanical failure (p=0.15). CONCLUSIONS: Among men with a replacement AUS, a history of pelvic radiation was associated with shorter time to device failure of any cause. Radiation was also specifically associated with a sevenfold increase in the risk of erosion or infection of replacement AUS, but not with urethral atrophy or mechanical failure. Patients with a replacement AUS should be appropriately counseled on how radiation history may impact outcomes of future revisions.


Assuntos
Incontinência Urinária por Estresse , Esfíncter Urinário Artificial , Atrofia , Feminino , Humanos , Masculino , Falha de Prótese , Reoperação/efeitos adversos , Reimplante/efeitos adversos , Estudos Retrospectivos , Medição de Risco , Resultado do Tratamento , Incontinência Urinária por Estresse/cirurgia , Esfíncter Urinário Artificial/efeitos adversos
18.
J Trauma Stress ; 35(2): 461-472, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34811818

RESUMO

Many returning military service members and veterans who were deployed following the September 11, 2001, terrorist attacks (9/11) suffer from posttraumatic stress disorder (PTSD) and insomnia. Although intensive treatment programs for PTSD have shown promise in the treatment of PTSD symptoms, recent research has demonstrated that sleep disturbance shows little improvement following intensive trauma-focused treatment. The aim of the present study was to evaluate changes in self-reported insomnia symptoms among veterans and service members following participation in a 2-week intensive program for PTSD. We further aimed to investigate if residual PTSD symptoms, specifically hyperarousal, were associated with residual insomnia symptoms. Participants (N = 326) completed self-report assessments of insomnia, PTSD symptoms, and depressive symptoms at pre- and posttreatment. At pretreatment, 73.9% of participants (n = 241) met the criteria for moderate or severe insomnia, whereas at posttreatment 67.7% of participants (n = 203) met the criteria. Results of paired t tests demonstrated statistically significant differences between pre- and posttreatment Insomnia Severity Index scores; however, the effect size was small, d = 0.34. Analyses revealed that posttreatment hyperarousal symptoms were associated with posttreatment insomnia. These findings suggest that although an intensive program for service members and veterans with PTSD may significantly reduce insomnia symptoms, clinically meaningful residual insomnia symptoms remain. Further research is warranted to elucidate the association between residual hyperarousal and insomnia symptoms following intensive trauma-focused treatment.


Assuntos
Distúrbios do Início e da Manutenção do Sono , Transtornos de Estresse Pós-Traumáticos , Veteranos , Nível de Alerta , Progressão da Doença , Humanos , Pacientes Ambulatoriais , Distúrbios do Início e da Manutenção do Sono/complicações , Distúrbios do Início e da Manutenção do Sono/terapia , Transtornos de Estresse Pós-Traumáticos/complicações , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/terapia
19.
Mil Psychol ; 34(6): 762-768, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-38536258

RESUMO

Suicide-bereaved military widows can struggle with posttraumatic stress disorder (PTSD) and prolonged grief. Intimate partner violence survivors (IPV) are particularly at risk. We examined whether IPV impacts outcomes in a two-week intensive outpatient program for N = 50 suicide-bereaved military widows. Mixed-model regressions were employed to examine the effects of IPV, time, and their interaction on symptoms. Thirty-four percent experienced IPV perpetrated by their deceased veteran. Symptoms improved at post-treatment (ps < .001), one-month (ps < .01), and three-month follow-up (ps< .001). There was no significant effect of IPV or significant interaction (ps > .05), indicating that IPV survivors also benefitted from treatment.

20.
Bio Protoc ; 11(21): e4236, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34859134

RESUMO

This protocol details a rapid and reliable method for the production and titration of high-titre viral pseudotype particles with the SARS-CoV-2 spike protein (and D614G or other variants of concern, VOC) on a lentiviral vector core, and use for neutralisation assays in target cells expressing angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). It additionally provides detailed instructions on substituting in new spike variants via gene cloning, lyophilisation and storage/shipping considerations for wide deployment potential. Results obtained with this protocol show that SARS-CoV-2 pseudotypes can be produced at equivalent titres to SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV) pseudotypes, neutralised by human convalescent plasma and monoclonal antibodies, and stored at a range of laboratory temperatures and lyophilised for distribution and subsequent application.

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