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1.
Cureus ; 16(6): e61895, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38975447

RESUMO

Retropharyngeal abscesses (RPAs) are rare in the adult population and rarer without an inciting event or comorbidity such as recent oral surgery, neck infection, or pharyngeal trauma. The definitive treatment is incision and drainage of the abscess. Clinical researchers have recently questioned whether invasive surgical intervention is necessary and posed the question of what role antibiotics play in management. Sequelae of RPAs are severe and include rupture of the abscess, erosion of the carotid artery, thrombophlebitis, and most seriously, airway compromise. We present a case where an atypical presentation of an RPA caused a disagreement among specialists, and the debate of whether the described case represented an abscess or malignancy caused a delay in diagnosis and treatment for the patient. Only after invasive and emergent surgical intervention was a final diagnosis able to be made. This case demonstrates the need for more research and official guidance on the management of new neck masses to hasten diagnosis and prevent devastating outcomes.

2.
bioRxiv ; 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38712111

RESUMO

The computation and comparison of subjective values underlying economic choices rely on the orbitofrontal cortex (OFC). In this area, distinct groups of neurons encode the value of individual options, the binary choice outcome, and the chosen value. These variables capture both the input and the output of the choice process, suggesting that the cell groups found in OFC constitute the building blocks of a decision circuit. Here we show that this neural circuit is longitudinally stable. Using two-photon calcium imaging, we recorded from mice choosing between different juice flavors. Recordings of individual cells continued for up to 20 weeks. For each cell and each pair of sessions, we compared the activity profiles using cosine similarity, and we assessed whether the cell encoded the same variable in both sessions. These analyses revealed a high degree of stability and a modest representational drift. A quantitative estimate indicated this drift would not randomize the circuit within the animal's lifetime.

3.
Int J Pharm Pract ; 32(1): 69-75, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38006341

RESUMO

OBJECTIVES: At the time of the survey, just over 2000 pharmacists were employed in UK general practice. Little is known about their influence on prescribing, and more specifically, the extent of their use of Audit and Feedback (A&F), an evidence-based method for behaviour change. This study aimed to explore pharmacists' current influence on prescribing in UK general practice. METHODS: A cross-sectional, online survey was open to general practice pharmacists in England, Northern Ireland, Scotland, and Wales between 9 September 2021 and 31 October 2021. The survey comprised 36 items, informed by the literature, including multiple choice and free-text questions about pharmacist responsibilities, involvement in prescribing audits (including use of A&F), use of prescribing guidelines, beliefs about influence on prescribing, and access to training and support. Descriptive statistics and frequencies were generated, and parametric analyses were conducted. KEY FINDINGS: In total, 155 responses were received from pharmacists in diverse practice locations, with a wide range of practice pharmacist experience. The majority (80%, n = 121) conducted prescribing audits, but only 21% (n = 32) reported undertaking A&F. Most respondents (90%, n = 140) used guidelines to inform their work, and 75% (n = 116) would welcome training on influencing prescribing. Pharmacists using A&F were more likely to believe in their ability to influence prescribing and to acknowledge this activity as part of their role. CONCLUSION: Despite substantial evidence of its effectiveness, A&F is under-used by practice pharmacists. An increased awareness and enablement of practice pharmacists in effective techniques might promote greater evidence-based prescribing in general practice.


Assuntos
Medicina Geral , Farmacêuticos , Humanos , Estudos Transversais , Inquéritos e Questionários , Medicina de Família e Comunidade , Escócia , Atitude do Pessoal de Saúde
4.
Artigo em Inglês | MEDLINE | ID: mdl-38028900

RESUMO

Objective: Characterize antibiotic prescribing behaviors at an Indian palliative care center after the initiation of the Antibiotic Order Form (AOF): an antibiotic stewardship program involving a paper form to track antibiotic use and to provide prescription guidelines. Design: Retrospective chart review. Setting: Trivandrum Institute of Palliative Sciences (TIPS) is a palliative care organization in Kerala, India. Methods: Antibiotic prescription data and patient data were collected for adult patients treated at TIPS between January 1, 2017, and October 31, 2019. Descriptive statistics and a Zero-Inflated Poisson regression model were used to analyze antibiotic prescriptions. AOF completion and prescription concordance with institutional guidelines were also evaluated. Results: Out of 7,450 unique patients, 675 (9%) were prescribed 1,448 antibiotics. Age was the strongest factor in determining the number of antibiotic courses with each additional year of age decreasing the expected antibiotic prescription count by 2% per year. The most common antibiotics prescribed were topical metronidazole (44%) and penicillins (29%). Among patients who died, 5% were prescribed antibiotics within the final month of life. In total, 32% of antibiotic prescriptions were documented in AOFs, and 18% were concordant with all institutional antibiotic prescribing guidelines. Conclusions: This study is the first to analyze an antibiotic stewardship intervention in a palliative care setting within a low- and middle-income country. This retrospective study provides a benchmark of antibiotic use within Indian palliative care and highlights areas for future stewardship research including topical metronidazole use within palliative care and higher rates of antibiotic use among younger palliative care patients.

5.
Proc Natl Acad Sci U S A ; 120(10): e2213034120, 2023 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-36857345

RESUMO

Primates can recognize features in virtually all types of images, an ability that still requires a comprehensive computational explanation. One hypothesis is that visual cortex neurons learn patterns from scenes, objects, and textures, and use these patterns to interpolate incoming visual information. We have used machine learning algorithms to instantiate visual patterns stored by neurons-we call these highly activating images prototypes. Prototypes from inferotemporal (IT) neurons often resemble parts of real-world objects, such as monkey faces and body parts, a similarity established via pretrained neural networks [C. R. Ponce et al., Cell 177, 999-1009.e10 (2019)] and naïve human participants [A. Bardon, W. Xiao, C. R. Ponce, M. S. Livingstone, G. Kreiman, Proc. Natl. Acad. Sci. U.S.A. 119, e2118705119 (2022)]. However, it is not known whether monkeys themselves perceive similarities between neuronal prototypes and real-world objects. Here, we investigated whether monkeys reported similarities between prototypes and real-world objects using a two-alternative forced choice task. We trained the animals to saccade to synthetic images of monkeys, and subsequently tested how they classified prototypes synthesized from IT and primary visual cortex (V1). We found monkeys classified IT prototypes as conspecifics more often than they did random generator images and V1 prototypes, and their choices were partially predicted by convolutional neural networks. Further, we confirmed that monkeys could abstract general shape information from images of real-world objects. Finally, we verified these results with human participants. Our results provide further evidence that prototypes from cortical neurons represent interpretable abstractions from the visual world.


Assuntos
Algoritmos , Macaca , Animais , Humanos , Apoptose , Formação de Conceito , Neurônios
6.
J Neurol Sci ; 446: 120564, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36731358

RESUMO

Alzheimer's disease (AD) is the most common form of dementia found in the elderly and disease progression is associated with accumulation of Amyloid beta 1-42 (Aß42) in brain. An immune-mediated approach as a preventive intervention to reduce amyloid plaques without causing brain inflammation is highly desirable for future clinical use. Genetic immunization, in which the immunizing agent is DNA encoding Aß42, has great potential because the immune response to DNA delivered into the skin is generally non-inflammatory, and thus differs quantitatively and qualitatively from immune responses elicited by peptides, which are inflammatory with production of IFNγ and IL-17 cytokines by activated T cells. DNA immunization has historically been proven difficult to apply to larger mammals. A potential barrier to use DNA immunization in large mammals is the method for delivery of the DNA antigen. We tested jet injection in mice and rabbits and found good antibody production and safe immune responses (no inflammatory cytokines). We found significant reduction of amyloid plaques and Aß peptides in brains of the DNA Aß42 immunized 3xTg-AD mouse model. This study was designed to optimize DNA delivery for possible testing of the DNA Aß42 vaccine for AD prevention in a clinical trial.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Camundongos , Coelhos , Animais , Peptídeos beta-Amiloides/metabolismo , Placa Amiloide , Fragmentos de Peptídeos , Imunoterapia , Encéfalo/metabolismo , Citocinas , Imunização/métodos , Injeções a Jato , DNA , Camundongos Transgênicos , Modelos Animais de Doenças , Mamíferos/genética , Mamíferos/metabolismo
7.
Viruses ; 15(2)2023 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-36851574

RESUMO

Oncolytic virotherapy constitutes a promising treatment option for many solid cancers, including peritoneal carcinomatosis (PC), which still represents a terminal stage of many types of tumors. To date, the in vitro efficacy of oncolytic viruses is mostly tested in 2D-cultured tumor cell lines due to the lack of realistic 3D in vitro tumor models. We have investigated the feasibility of virotherapy as a treatment option for PC in a human ex vivo peritoneum co-culture model. Human HT-29 cancer cells stably expressing marker genes GFP and firefly luciferase (GFP/luc) were cultured on human peritoneum and infected with two prototypic oncolytic viruses (GLV-0b347 and MeV-DsRed). Both viral constructs were able to infect HT-29 cells in patient-derived peritoneum with high tumor specificity. Over time, both GFP signal and luciferase activity decreased substantially, thereby indicating successful virus-induced oncolysis. Furthermore, immunohistochemistry stainings showed specific virotherapeutic infections of HT-29 cells and effective tumor cell lysis in infected co-cultures. Thus, the PC model established here provides a clinically relevant screening platform to evaluate the therapeutic efficacy of virotherapeutic compounds and also to investigate, in an autologous setting, the immunostimulatory potential of oncolytic viruses for PC in a unique human model system superior to standard 2D in vitro models.


Assuntos
Terapia Viral Oncolítica , Vírus Oncolíticos , Neoplasias Peritoneais , Humanos , Neoplasias Peritoneais/terapia , Vírus Oncolíticos/genética , Morte Celular , Técnicas de Cocultura
8.
Fam Pract ; 40(5-6): 615-628, 2023 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-36633309

RESUMO

INTRODUCTION: Pharmacists, as experts in medicines, are increasingly employed in general practices and undertake a range of responsibilities. Audit and feedback (A&F) interventions are effective in achieving behaviour change, including prescribing. The extent of pharmacist involvement in A&F interventions to influence prescribing is unknown. This review aimed to assess the effectiveness of A&F interventions involving pharmacists on prescribing in general practice compared with no A&F/usual care and to describe features of A&F interventions and pharmacist characteristics. METHODS: Electronic databases (MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, (Social) Science Citation Indexes, ISI Web of Science) were searched (2012, 2019, 2020). Cochrane systematic review methods were applied to trial identification, selection, and risk of bias. Results were summarized descriptively and heterogeneity was assessed. A random-effects meta-analysis was conducted where studies were sufficiently homogenous in design and outcome. RESULTS: Eleven cluster-randomized studies from 9 countries were included. Risk of bias across most domains was low. Interventions focussed on older patients, specific clinical area(s), or specific medications. Meta-analysis of 6 studies showed improved prescribing outcomes (pooled risk ratio: 0.78, 95% confidence interval: 0.64-0.94). Interventions including both verbal and written feedback or computerized decision support for prescribers were more effective. Pharmacists who received study-specific training, provided ongoing support to prescribers or reviewed prescribing for individual patients, contributed to more effective interventions. CONCLUSIONS: A&F interventions involving pharmacists can lead to small improvements in evidence-based prescribing in general practice settings. Future implementation of A&F within general practice should compare different ways of involving pharmacists to determine how to optimize effectiveness.PRISMA-compliant abstract included in Supplementary Material 1.


Assuntos
Medicina Geral , Farmacêuticos , Humanos , Retroalimentação , Medicina de Família e Comunidade
9.
Cureus ; 14(10): e30527, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36415356

RESUMO

Gastroparesis is a known complication in patients with diabetes mellitus (DM). This disorder has been known to make glycemic control difficult due to diabetic autonomic neuropathy, resulting in an increase in hypoglycemic episodes. On occasion, gastroparesis may be so severe that prokinetic medications and gastric pacemakers are not sufficient to control the symptoms, in which case some patients need to supplement their diet through a jejunal tube (J-tube) to bypass the stomach. Severe or long-lasting hypoglycemia may rarely be associated with epileptic seizures. We present a case of a 47-year-old female with a history significant for type 1 DM complicated by gastroparesis requiring a gastric pacemaker and J-tube placement who presented to the emergency department after having a witnessed seizure. Her glucose at that time was 27 mg/dl (normal 70-110 mg/dl) and she was treated appropriately with dextrose 25% solution and her glucose recovered to 110 mg/dl. Subsequently, seizure activity ceased.

10.
Front Oncol ; 12: 995744, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36387105

RESUMO

NUT carcinoma (NC) is a rare and extremely aggressive form of cancer, usually presenting with intrathoracic or neck manifestations in adolescents and young adults. With no established standard therapy regimen and a median overall survival of only 6.5 months, there is a huge need for innovative treatment options. As NC is genetically driven by a single aberrant fusion oncoprotein, it is generally characterized by a low tumor mutational burden, thus making it immunologically cold and insusceptible to conventional immunotherapy. Recently, we have demonstrated that oncolytic viruses (OVs) are able to specifically infect and lyse NC cells, thereby turning an immunologically cold tumor microenvironment into a hot one. Here, we report an intensive multimodal treatment approach employing for the first time an OV (talimogene laherparepvec (T-VEC); IMLYGIC®) together with the immune checkpoint inhibitor pembrolizumab as an add-on to a basic NC therapy (cytostatic chemotherapy, radiation therapy, epigenetic therapy) in a patient suffering from a large thoracic NC tumor which exhibits an aberrant, unique BRD3:NUTM1 fusion. This case demonstrates for the first time the feasibility of this innovative add-on immunovirotherapy regimen with a profound, repetitive and durable replication of T-VEC that is instrumental in achieving tumor stabilization and improvement in the patient´s quality of life. Further, a previously unknown BRD3:NUTM1 fusion gene was discovered that lacks the extraterminal domain of BRD3.

11.
Nucl Med Biol ; 114-115: 78-85, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36270073

RESUMO

The number of non-melanoma skin cancer (NMSC) cases in the US will increase significantly over the next decade due to a rise in UV exposure. One of the treatment methods used to remove NMSC lesions is radiation therapy. The two types of radiation therapy used in the clinic are external beam therapy and brachytherapy. However, both require specialized on-site instrumentation and for patients to remain immobile. In this work, we studied an alternative radiation therapy - one that does not require expensive on-site equipment and would allow for enhanced patient mobility and, thus, comfort. We prepared sealed source, nylon-laminated holmium-166-containing radiotherapeutic bandages and used them in C3H/HeN mice with murine SCCVII tumor grafts. Overall, tumor sizes were smallest when treated with therapeutically relevant radiation doses via radiotherapeutic bandages (compared to controls), and no histological evidence of toxicity to tissues was observed. Thus, our optimized radiotherapeutic bandage offers a flexible approach to treating NMSC.


Assuntos
Neoplasias Cutâneas , Animais , Camundongos , Camundongos Endogâmicos C3H , Neoplasias Cutâneas/radioterapia , Neoplasias Cutâneas/patologia , Hólmio , Bandagens
12.
Ann Med Surg (Lond) ; 78: 103920, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35734710

RESUMO

Introduction: and Importance: Melanomas are capable of metastasizing to both regional and distant sites and are notably known to metastasize to the skin, lungs, brain, liver, bone, and gastrointestinal tract. Metastatic melanoma is infrequently diagnosed in vivo, and usually found only on post-mortem evaluation at autopsy. Case Presentation: Here we present the case of a 64-year-old male who originally presented with melena, fatigue, exertional dyspnea and one episode of near-syncope. He was found to have a hemoglobin of 5.4 gm/dL on initial presentation with largely unremarkable abdominal examination. CTAP demonstrated an area of circumferential small bowel wall thickening, concerning for malignancy. The patient underwent an EGD that was noted for mild gastric fundal erosions, which failed to explain his presenting symptoms. VCE was later performed following discharge to visualize the small bowel, which revealed two bleeding lesions within the small bowel. This was complicated by the device becoming lodged on the more proximal mass, and he was admitted again for push-enteroscopy and device retrieval. At the time of this admission, he continued to be symptomatic and was profoundly anemic with a hemoglobin of 4.7 gm/dL. Clinical Discussion: EGD with push enteroscopy was performed, revealing two small masses in the mid-distal duodenum and jejunum, which were tattooed and biopsied. He underwent robotic-assisted laparoscopic small bowel resection of the affected portions of the small bowel, without complications. Surgical samples were consistent with melanoma, and further dermatologic examination revealed a suspicious lesion located on the patient's posterior right shoulder was biopsied and also consistent with melanoma, confirming the suspicion for metastatic process from primary cutaneous lesion. Conclusions: We present this case as a rare diagnostic opportunity to observe metastatic melanoma of the small bowel, including a review of pertinent symptomatology and epidemiological data from previous literature. Our case serves as a reminder to consider metastatic melanoma as a rather uncommon cause of severe blood loss anemia, while also providing an overview of endoscopic modalities available for visualizing the small bowel in the management of suspected small bowel malignancy.

13.
Science ; 376(6598): 1192-1202, 2022 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-35511946

RESUMO

Caloric restriction (CR) prolongs life span, yet the mechanisms by which it does so remain poorly understood. Under CR, mice self-impose chronic cycles of 2-hour feeding and 22-hour fasting, raising the question of if it is calories, fasting, or time of day that is the cause of this increased life span. We show here that 30% CR was sufficient to extend the life span by 10%; however, a daily fasting interval and circadian alignment of feeding acted together to extend life span by 35% in male C57BL/6J mice. These effects were independent of body weight. Aging induced widespread increases in gene expression associated with inflammation and decreases in the expression of genes encoding components of metabolic pathways in liver from ad libitum-fed mice. CR at night ameliorated these aging-related changes. Our results show that circadian interventions promote longevity and provide a perspective to further explore mechanisms of aging.


Assuntos
Restrição Calórica , Ritmo Circadiano , Longevidade , Animais , Regulação da Expressão Gênica , Longevidade/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL
14.
J Neurosurg ; 137(6): 1676-1686, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-35426830

RESUMO

OBJECTIVE: There is an unmet need for safe and rapidly effective therapies for refractory brain radiation necrosis (RN). The aim of this prospective single-arm phase II trial was to evaluate the safety and efficacy of a single low-dose targeted bevacizumab infusion after blood-brain barrier disruption (BBBD) in adult patients with steroid-refractory brain RN. METHODS: Ten adults with steroid-refractory, imaging-confirmed brain RN were enrolled between November 2016 and January 2018 and followed for 12 months after treatment. Bevacizumab 2.5 mg/kg was administered as a one-time targeted intra-arterial infusion immediately after BBBD. Primary outcomes included safety and > 25% decrease in lesion volume. Images were analyzed by a board-certified neuroradiologist blinded to pretrial diagnosis and treatment status. Secondary outcomes included changes in headache, steroid use, and functional status and absence of neurocognitive sequelae. Comparisons were analyzed using the Fisher exact test, Mann-Whitney U-test, linear mixed models, Wilcoxon signed-rank test, and repeated-measures 1-way ANOVA. RESULTS: Ten adults (mean ± SD [range] age 35 ± 15 [22-62] years) participated in this study. No patients died or exhibited serious adverse effects of systemic bevacizumab. At 3 months, 80% (95% CI 44%-98%) and 90% (95% CI 56%-100%) of patients demonstrated > 25% decrease in RN and vasogenic edema volume, respectively. At 12 months, RN volume decreased by 74% (median [range] 76% [53%-96%], p = 0.012), edema volume decreased by 50% (median [range] 70% [-11% to 83%], p = 0.086), and headache decreased by 84% (median [range] 92% [58%-100%], p = 0.022) among the 8 patients without RN recurrence. Only 1 (10%) patient was steroid dependent at the end of the trial. Scores on 12 of 16 (75%) neurocognitive indices increased, thereby supporting a pattern of cerebral white matter recovery. Two (20%) patients exhibited RN recurrence that required further treatment at 10 and 11 months, respectively, after bevacizumab infusion. CONCLUSIONS: For the first time, to the authors' knowledge, the authors demonstrated that a single low-dose targeted bevacizumab infusion resulted in durable clinical and imaging improvements in 80% of patients at 12 months after treatment without adverse events attributed to bevacizumab alone. These findings highlight that targeted bevacizumab may be an efficient one-time treatment for adults with brain RN. Further confirmation with a randomized controlled trial is needed to compare the intra-arterial approach with the conventional multicycle intravenous regimen. Clinical trial registration no.: NCT02819479 (ClinicalTrials.gov).


Assuntos
Neoplasias Encefálicas , Lesões por Radiação , Radiocirurgia , Adulto , Humanos , Adulto Jovem , Pessoa de Meia-Idade , Bevacizumab/uso terapêutico , Estudos Prospectivos , Lesões por Radiação/etiologia , Encéfalo/patologia , Radiocirurgia/métodos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/patologia , Necrose/etiologia , Edema/tratamento farmacológico , Esteroides , Cefaleia/etiologia
15.
Cureus ; 14(2): e22282, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35350491

RESUMO

Severe acute respiratory syndrome coronavirus (SARS-CoV-2), primarily a respiratory virus, has also presented with cardiac complications including myocarditis, myocardial infarction, and cardiac arrhythmias. Pericardial effusions are also emerging in the literature as a sequel to this viral infection. A case of a 57-year-old Hispanic female with SARS-CoV-2 infection two months prior with worsening dyspnea on exertion who was found to have a large hemorrhagic pericardial effusion with early tamponade physiology was presented in this article. This case highlights the rare complication and the importance of bedside echocardiogram in patients with recent SARS-CoV-2 infection who present with shortness of breath and other signs of pericardial effusion.

16.
Front Mol Biosci ; 9: 826302, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35223990

RESUMO

Background: Although several oncolytic viruses have already been tested in early-stage clinical studies of breast cancer, there is still an urgent need to develop patient-derived experimental systems that mimic the response of breast cancer to oncolytic agents in preparation of testing different oncolytic viruses in clinical trials. We addressed this need by developing a protocol to study the effects of oncolytic viruses in stable organoid cell cultures derived from breast cancer tissue. Methods: We used an established three-dimensional organoid model derived from tissue of 10 patients with primary breast cancer. We developed an experimental protocol for infecting organoid cultures with oncolytic viruses and compared the oncolytic effects of a measles vaccine virus (MeV) and a vaccinia virus (GLV) genetically engineered to express either green fluorescent protein (MeV-GFP) and red fluorescent protein (GLV-0b347), respectively, or a suicide gene encoding a fusion of cytosine deaminase with uracil phosphoribosyltransferase (MeV-SCD and GLV-1h94, respectively), thereby enabling enzymatic conversion of the prodrug 5-fluorocytosine (5-FC) into cytotoxic compounds 5-fluorouracil (5-FU) and 5-fluorouridine monophosphate (5-FUMP). Results: The method demonstrated that all oncolytic viruses significantly inhibited cell viability in organoid cultures derived from breast cancer tissue. The oncolytic effects of the oncolytic viruses expressing suicide genes (MeV-SCD and GLV-1h94) were further enhanced by virus-triggered conversion of the prodrug 5-FC to toxic 5-FU and toxic 5-FUMP. Conclusions: We were able to develop a protocol to assess the effects of two different types of oncolytic viruses in stable organoid cell cultures derived from breast cancer tissue. The greatest oncolytic effects were observed when the oncolytic viruses were engineered to express a suicide gene (MeV-SCD and GLV-1h94) in the presence of the prodrug 5-FC. The model therefore provides a promising in vitro method to help further testing and engineering of new generations of virotherapeutic vectors for in vivo use.

17.
Proc Natl Acad Sci U S A ; 118(49)2021 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-34873063

RESUMO

Flaviviruses such as Zika virus and West Nile virus have the potential to cause severe neuropathology if they invade the central nervous system. The type I interferon response is well characterized as contributing to control of flavivirus-induced neuropathogenesis. However, the interferon-stimulated gene (ISG) effectors that confer these neuroprotective effects are less well studied. Here, we used an ISG expression screen to identify Shiftless (SHFL, C19orf66) as a potent inhibitor of diverse positive-stranded RNA viruses, including multiple members of the Flaviviridae (Zika, West Nile, dengue, yellow fever, and hepatitis C viruses). In cultured cells, SHFL functions as a viral RNA-binding protein that inhibits viral replication at a step after primary translation of the incoming genome. The murine ortholog, Shfl, is expressed constitutively in multiple tissues, including the central nervous system. In a mouse model of Zika virus infection, Shfl-/- knockout mice exhibit reduced survival, exacerbated neuropathological outcomes, and increased viral replication in the brain and spinal cord. These studies demonstrate that Shfl is an important antiviral effector that contributes to host protection from Zika virus infection and virus-induced neuropathological disease.


Assuntos
Proteínas de Ligação a RNA/metabolismo , Infecção por Zika virus/patologia , Zika virus/metabolismo , Animais , Linhagem Celular , Efeito Citopatogênico Viral , Modelos Animais de Doenças , Suscetibilidade a Doenças/metabolismo , Suscetibilidade a Doenças/virologia , Flavivirus/genética , Infecções por Flavivirus/genética , Infecções por Flavivirus/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fármacos Neuroprotetores/metabolismo , Proteínas de Ligação a RNA/genética , Replicação Viral/fisiologia , Zika virus/patogenicidade , Infecção por Zika virus/genética
18.
Cureus ; 13(9): e18017, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34667692

RESUMO

Acquired thrombotic thrombocytopenic purpura (TTP) is an uncommon microangiopathic disorder that can have variable presentations and can be precipitated by a multitude of stressors to the body, most commonly sepsis. TTP is caused by a deficiency of ADAMTS13 leading to intravascular clotting causing thrombocytopenia and microangiopathic hemolytic anemia. TTP can be associated with various other pathologic conditions. One such rare association has been reported with diabetic ketoacidosis (DKA). Here, we present an even less appreciated presentation in association with DKA. A 62-year-old African American male with previously diagnosed prediabetes presented with DKA and developed hemodynamically significant bleeding. He was confirmed to have TTP that responded to plasmapheresis. TTP is a life-threatening illness if not treated urgently with plasmapheresis with or without rituximab. As acquired TTP most commonly occurs during stress on the body, it is important to treat the underlying stressor. Early identification and initiation of appropriate interventions are crucial to reducing mortality associated with TTP. Furthermore, we need to appreciate less commonly associated conditions such as DKA among patients.

19.
Geriatr Nurs ; 42(6): 1356-1361, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34562808

RESUMO

The purpose of the study was to examine trends in COVID-19 cases, related deaths, and staffing shortages in nursing homes (NH) by rural and urban status from May 2020 to Feb 2021. Generalized linear mixed models with state-fixed effects were used to estimate the interaction effect of study period and rural/urban status on having at least: one COVID-19 case, one related death, and/or at least one week of staffing shortage using the NH COVID-19 data spanning the 40-week period. The findings revealed shortages in staff, particularly direct care providers, were greatly accelerated in rural NHs as the pandemic wore on over time. Conversely, staffing shortages in urban NHs were relatively stable despite the fluctuating COVID-19 cases over the same time period. The findings highlight the need of identifying effective strategies that prevent rural NHs from encountering staffing deficits in response to long-lasting natural disasters such as the COVID-19 pandemic.


Assuntos
COVID-19 , Humanos , Casas de Saúde , Pandemias , SARS-CoV-2 , Estados Unidos , Recursos Humanos
20.
Front Psychol ; 12: 669899, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220642

RESUMO

Community groups are commonly used as a mode of delivery of interventions for promoting health and well-being. Research has demonstrated that developing a sense of shared social identity with other group members is a key mechanism through which the health benefits of group membership are realized. However, there is little understanding of how shared social identity emerges within these therapeutic settings. Understanding the emergence of shared social identity may help researchers optimize interventions and improve health outcomes. Group-based singing activities encourage coordination and a shared experience, and are a potential platform for the development of shared social identity. We use the "Singing for People with Aphasia" (SPA) group intervention to explore whether group cohesiveness, as a behavioral proxy for shared social identity, can be observed and tracked across the intervention. Video recordings of group sessions from three separate programmes were rated according to the degree of cohesiveness exhibited by the group. For all treatment groups, the final group session evidenced reliably higher levels of cohesiveness than the first session (t values ranged from 4.27 to 7.07; all p values < 0.003). As well as providing confidence in the design and fidelity of this group-based singing intervention in terms of its capacity to build shared social identity, this evaluation highlighted the value of observational methods for the analysis of shared social identity in the context of group-based singing interventions.

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