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2.
J Contin Educ Nurs ; 54(4): 157-168, 2023 Apr.
Article in English | MEDLINE | ID: covidwho-2279617

ABSTRACT

Caring for older persons is a challenge for professionals who work in nursing homes. Problems in maintaining effective communication with a person with dementia in an effort to understand their needs is a major barrier to good care. Therefore, the main goals of this study were to explore communication barriers between professionals and people with dementia and to observe changes in communication patterns between them after completing Naomi Feil's introductory training in the bases of the validation method (BVM). The 11 professionals who worked in nursing homes attended a 16-hour introductory course on BVM. Participants were interviewed individually three times. The goal was to observe qualitatively the changes in relationships and communication patterns with people with dementia. The results were analyzed thematically. The professionals highlighted how, after the training, they had a different understanding of the person with dementia and a more humane perspective. These changes also reflected how the professionals experienced improvements in job satisfaction, security, and confidence. This study concluded that training nursing home staff in BVM for person-centered and human care has positive implications on how the professionals view their daily work and their way of interacting with older residents. [J Contin Educ Nurs. 2023;54(4):157-168.].


Subject(s)
Dementia , Nursing Staff , Humans , Aged , Aged, 80 and over , Homes for the Aged , Nursing Homes , Nursing Staff/education , Communication
3.
SAGE Open Med ; 11: 20503121231162339, 2023.
Article in English | MEDLINE | ID: covidwho-2284355

ABSTRACT

Objective: To evaluate and validate the medically necessary and time sensitive score by testing the variables, in order to create a surgical preoperative score for procedure prioritization in COVID-19 pandemic in Colombia. Methods: A multicenter retrospective cross-sectional study of instrument validation with a cultural adaptation and translation into the Spanish language was carried out in Bogota, Colombia. Patients over 18 years of age who had undergone elective procedures of general surgery and subspecialties were included. The translation of the medically necessary and time sensitive score into Spanish was performed independently by two bilingual surgeons fluent in both English and Spanish. A final version of the Spanish questionnaire (MeNTS Col) for testing was then produced by an expert committee. After translation and cultural adaptation, it was submitted to evaluate the psychometric properties of the medically necessary and time sensitive score. Cronbach's α was used to represent and evaluate the internal consistency and assess reliability. Results: A total of 172 patients were included, with a median age of 54 years; of which 96 (55.8%) patients were females. The vast majority of patients were treated for general surgery (n = 60) and colon and rectal surgery (n = 31). The evaluation of the internal consistency of the scale items in Spanish version was measured, and values of 0.5 for 0.8 were obtained. In the reliability and validation process, Cronbach's α values in all items remained higher than 0.7. The new MeNTS Col model was analyzed, and a result of 0.91 was obtained. Conclusions: The Spanish version of the medically necessary and time sensitive, the MeNTS Col score, and its respective Spanish translation perform similarly to the original version. Therefore, they can be useful and reproducible in Latin American countries.

4.
J R Coll Physicians Edinb ; 51(2): 199-207, 2021 06.
Article in English | MEDLINE | ID: covidwho-2202476
5.
Rev. Fac. Med. Hum ; 22(4): 833-840, octubre-diciembre 2022.
Article in English, Spanish | WHO COVID, LILACS (Americas) | ID: covidwho-2205413

ABSTRACT

Critical syndromes are conditions that carry a high global burden of disease. Scoring systems are practical and reproducible aids that allow patients with more severe disease to be quickly identified and admitted to intensive care and to initiate structured and aggressive therapy. The Sequential Organ Failure Assessment (SOFA) score is one of the most widely used in the world, as there are several versions and it is simple. However, with the appearance of the COVID-19, several studies showed that there was a disparity in the estimation of mortality and associated outcomes, with respect to race, which culminated in an excess of preventable mortality in certain racial groups. Constant evaluation of the performance of these scoring systems must be performed due to definitional updates, which may vary the accuracy of the predictive value. There is a very large evidence gap in this regard, as the existing studies are from high-income countries where the predominant racial group is Caucasian, which should draw attention to the magnitude of the problem. Based on the above, the objective of this review is to discuss evidence on the performance of critical care scoring systems, particularly SOFA, and the impact that race has had on its predictive value.


Los síndromes críticos son condiciones que acarrean una elevada carga de enfermedad a nivel global. Los sistemas de puntaje, son ayudas prácticas y reproducibles que permiten identificar de manera rápida pacientes con enfermedad más grave e ingresarlos a cuidado intensivo e iniciar terapia estructurada y agresiva. El score Sequential Organ Failure Assessment (SOFA), es uno de los más utilizados en el mundo, al existir varias versiones y ser sencillo. No obstante, con la aparición de la COVID-19, diversos estudios demostraron que existía una disparidad en cuanto a la estimación de mortalidad y desenlaces asociados, respecto a la raza, lo que culminó en un exceso de mortalidad prevenible en ciertos grupos raciales. La evaluación constante del rendimiento de estos sistemas de puntaje, debe realizarse debido a actualizaciones de definiciones, las cuales pueden variar la precisión del valor predictivo. Existe una brecha muy grande en cuanto la evidencia al respecto, puesto que los estudios existentes provienen de países de altos ingresos, donde el grupo racial predominante son los caucásicos, lo que debe llamar la atención de la magnitud del problema. Sobre la base de lo anterior, el objetivo de esta revisión consiste en discutir evidencia al respecto sobre el rendimiento de sistemas de puntuación en cuidado crítico, particularmente del SOFA y el impacto que ha tenido la raza sobre su valor predictivo.

6.
Biomolecules ; 12(11)2022 11 11.
Article in English | MEDLINE | ID: covidwho-2109923

ABSTRACT

BACKGROUND: SARS-CoV-2 has undergone mutations, yielding clinically relevant variants. HYPOTHESIS: We hypothesized that in SARS-CoV-2, two highly conserved Orf3a and E channels directly related to the virus replication were a target for the detection and inhibition of the viral replication, independent of the variant, using FDA-approved ion channel modulators. METHODS: A combination of a fluorescence potassium ion assay with channel modulators was developed to detect SARS-CoV-2 Orf3a/E channel activity. Two FDA-approved drugs, amantadine (an antiviral) and amitriptyline (an antidepressant), which are ion channel blockers, were tested as to whether they inhibited Orf3a/E channel activity in isolated virus variants and in nasal swab samples from COVID-19 patients. The variants were confirmed by PCR sequencing. RESULTS: In isolated SARS-CoV-2 Alpha, Beta, and Delta variants, the channel activity of Orf3a/E was detected and inhibited by emodin and gliclazide (IC50 = 0.42 mM). In the Delta swab samples, amitriptyline and amantadine inhibited the channel activity of viral proteins, with IC50 values of 0.73 mM and 1.11 mM, respectively. In the Omicron swab samples, amitriptyline inhibited the channel activity, with an IC50 of 0.76 mM. CONCLUSIONS: We developed an efficient method to screen FDA-approved ion channel modulators that could be repurposed to detect and inhibit SARS-CoV-2 viral replication, independent of variants.


Subject(s)
COVID-19 Drug Treatment , Ion Channels , SARS-CoV-2 , Humans , Amantadine/pharmacology , Amitriptyline/pharmacology , Ion Channels/antagonists & inhibitors , SARS-CoV-2/drug effects , Drug Evaluation, Preclinical , Drug Repositioning
7.
N Biotechnol ; 72: 11-21, 2022 Aug 08.
Article in English | MEDLINE | ID: covidwho-2049684

ABSTRACT

Developing affordable and easily manufactured SARS-CoV-2 vaccines will be essential to achieve worldwide vaccine coverage and long-term control of the COVID-19 pandemic. Here the development is reported of a vaccine based on the SARS-CoV-2 receptor-binding domain (RBD), produced in the yeast Pichia pastoris. The RBD was modified by adding flexible N- and C-terminal amino acid extensions that modulate protein/protein interactions and facilitate protein purification. A fed-batch methanol fermentation with a yeast extract-based culture medium in a 50 L fermenter and an immobilized metal ion affinity chromatography-based downstream purification process yielded 30-40 mg/L of RBD. Correct folding of the purified protein was demonstrated by mass spectrometry, circular dichroism, and determinations of binding affinity to the angiotensin-converting enzyme 2 (ACE2) receptor. The RBD antigen also exhibited high reactivity with sera from convalescent individuals and Pfizer-BioNTech or Sputnik V vaccinees. Immunization of mice and non-human primates with 50 µg of the recombinant RBD adjuvanted with alum induced high levels of binding antibodies as assessed by ELISA with RBD produced in HEK293T cells, and which inhibited RBD binding to ACE2 and neutralized infection of VeroE6 cells by SARS-CoV-2. Additionally, the RBD protein stimulated IFNγ, IL-2, IL-6, IL-4 and TNFα secretion in splenocytes and lung CD3+-enriched cells of immunized mice. The data suggest that the RBD recombinant protein produced in yeast P. pastoris is suitable as a vaccine candidate against COVID-19.

8.
Front Immunol ; 13: 948431, 2022.
Article in English | MEDLINE | ID: covidwho-2022730

ABSTRACT

Emergence of variants of concern (VOC) during the COVID-19 pandemic has contributed to the decreased efficacy of therapeutic monoclonal antibody treatments for severe cases of SARS-CoV-2 infection. In addition, the cost of creating these therapeutic treatments is high, making their implementation in low- to middle-income countries devastated by the pandemic very difficult. Here, we explored the use of polyclonal EpF(ab')2 antibodies generated through the immunization of horses with SARS-CoV-2 WA-1 RBD conjugated to HBsAg nanoparticles as a low-cost therapeutic treatment for severe cases of disease. We determined that the equine EpF(ab')2 bind RBD and neutralize ACE2 receptor binding by virus for all VOC strains tested except Omicron. Despite its relatively quick clearance from peripheral circulation, a 100µg dose of EpF(ab')2 was able to fully protect mice against severe disease phenotypes following intranasal SARS-CoV-2 challenge with Alpha and Beta variants. EpF(ab')2 administration increased survival while subsequently lowering disease scores and viral RNA burden in disease-relevant tissues. No significant improvement in survival outcomes or disease scores was observed in EpF(ab')2-treated mice challenged using the Delta variant at 10µg or 100µg doses. Overall, the data presented here provide a proof of concept for the use of EpF(ab')2 in the prevention of severe SARS-CoV-2 infections and underscore the need for either variant-specific treatments or variant-independent therapeutics for COVID-19.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , COVID-19/prevention & control , Horses , Humans , Immunization, Passive , Melphalan , Mice , Pandemics , SARS-CoV-2/genetics , gamma-Globulins
9.
PLoS One ; 17(8): e0273430, 2022.
Article in English | MEDLINE | ID: covidwho-2021918

ABSTRACT

The COVID-19 pandemic has been fueled by SARS-CoV-2 novel variants of concern (VOC) that have increased transmissibility, receptor binding affinity, and other properties that enhance disease. The goal of this study is to characterize unique pathogenesis of the Delta VOC strain in the K18-hACE2-mouse challenge model. Challenge studies suggested that the lethal dose of Delta was higher than Alpha or Beta strains. To characterize the differences in the Delta strain's pathogenesis, a time-course experiment was performed to evaluate the overall host response to Alpha or Delta variant challenge. qRT-PCR analysis of Alpha- or Delta-challenged mice revealed no significant difference between viral RNA burden in the lung, nasal wash or brain. However, histopathological analysis revealed high lung tissue inflammation and cell infiltration following Delta- but not Alpha-challenge at day 6. Additionally, pro-inflammatory cytokines were highest at day 6 in Delta-challenged mice suggesting enhanced pneumonia. Total RNA-sequencing analysis of lungs comparing challenged to no challenge mice revealed that Alpha-challenged mice have more total genes differentially activated. Conversely, Delta-challenged mice have a higher magnitude of differential gene expression. Delta-challenged mice have increased interferon-dependent gene expression and IFN-γ production compared to Alpha. Analysis of TCR clonotypes suggested that Delta challenged mice have increased T-cell infiltration compared to Alpha challenged. Our data suggest that Delta has evolved to engage interferon responses in a manner that may enhance pathogenesis. The in vivo and in silico observations of this study underscore the need to conduct experiments with VOC strains to best model COVID-19 when evaluating therapeutics and vaccines.


Subject(s)
COVID-19 , Pneumonia , Animals , Antiviral Agents , COVID-19/genetics , Disease Models, Animal , Humans , Interferons , Melphalan , Mice , Mice, Transgenic , Pandemics , SARS-CoV-2 , gamma-Globulins
10.
iScience ; 25(10): 105038, 2022 Oct 21.
Article in English | MEDLINE | ID: covidwho-2007777

ABSTRACT

Severe outcomes from SARS-CoV-2 infection are highly associated with preexisting comorbid conditions like hypertension, diabetes, and obesity. We utilized the diet-induced obesity (DIO) model of metabolic dysfunction in K18-hACE2 transgenic mice to model obesity as a COVID-19 comorbidity. Female DIO, but not male DIO mice challenged with SARS-CoV-2 were observed to have shortened time to morbidity compared to controls. Increased susceptibility to SARS-CoV-2 in female DIO was associated with increased viral RNA burden and interferon production compared to males. Transcriptomic analysis of the lungs from all mouse cohorts revealed sex- and DIO-associated differential gene expression profiles. Male DIO mice after challenge had decreased expression of antibody-related genes compared to controls, suggesting antibody producing cell localization in the lung. Collectively, this study establishes a preclinical comorbidity model of COVID-19 in mice where we observed sex- and diet-specific responses that begin explaining the effects of obesity and metabolic disease on COVID-19 pathology.

11.
Int J Mol Sci ; 23(17)2022 Aug 30.
Article in English | MEDLINE | ID: covidwho-2006046

ABSTRACT

Sialic acids and heparan sulfates make up the outermost part of the cell membrane and the extracellular matrix. Both structures are characterized by being negatively charged, serving as receptors for various pathogens, and are highly expressed in the respiratory and digestive tracts. Numerous viruses use heparan sulfates as receptors to infect cells; in this group are HSV, HPV, and SARS-CoV-2. Other viruses require the cell to express sialic acids, as is the case in influenza A viruses and adenoviruses. This review aims to present, in a general way, the participation of glycoconjugates in viral entry, and therapeutic strategies focused on inhibiting the interaction between the virus and the glycoconjugates. Interestingly, there are few studies that suggest the participation of both glycoconjugates in the viruses addressed here. Considering the biological redundancy that exists between heparan sulfates and sialic acids, we propose that it is important to jointly evaluate and design strategies that contemplate inhibiting the interactions of both glycoconjugates. This approach will allow identifying new receptors and lead to a deeper understanding of interspecies transmission.


Subject(s)
COVID-19 , Viruses , Glycoconjugates/metabolism , Heparitin Sulfate/metabolism , Humans , N-Acetylneuraminic Acid/metabolism , Receptors, Virus/metabolism , SARS-CoV-2 , Sialic Acids/metabolism , Sulfates , Virus Attachment , Viruses/metabolism
12.
mSphere ; 7(4): e0024322, 2022 08 31.
Article in English | MEDLINE | ID: covidwho-1992945

ABSTRACT

The ongoing COVID-19 pandemic has contributed largely to the global vaccine disparity. Development of protein subunit vaccines can help alleviate shortages of COVID-19 vaccines delivered to low-income countries. Here, we evaluated the efficacy of a three-dose virus-like particle (VLP) vaccine composed of hepatitis B surface antigen (HBsAg) decorated with the receptor binding domain (RBD) from the Wuhan or Beta SARS-CoV-2 strain adjuvanted with either aluminum hydroxide (alum) or squalene in water emulsion (SWE). RBD HBsAg vaccines were compared to the standard two doses of Pfizer mRNA vaccine. Alum-adjuvanted vaccines were composed of either HBsAg conjugated with Beta RBD alone (ß RBD HBsAg+Al) or a combination of both Beta RBD HBsAg and Wuhan RBD HBsAg (ß/Wu RBD HBsAg+Al). RBD vaccines adjuvanted with SWE were formulated with Beta RBD HBsAg (ß RBD HBsAg+SWE) or without HBsAg (ß RBD+SWE). Both alum-adjuvanted RBD HBsAg vaccines generated functional RBD IgG against multiple SARS-CoV-2 variants of concern (VOC), decreased viral RNA burden, and lowered inflammation in the lung against Alpha or Beta challenge in K18-hACE2 mice. However, only ß/Wu RBD HBsAg+Al was able to afford 100% survival to mice challenged with Alpha or Beta VOC. Furthermore, mice immunized with ß RBD HBsAg+SWE induced cross-reactive neutralizing antibodies against major VOC of SARS-CoV-2, lowered viral RNA burden in the lung and brain, and protected mice from Alpha or Beta challenge similarly to mice immunized with Pfizer mRNA. However, RBD+SWE immunization failed to protect mice from VOC challenge. Our findings demonstrate that RBD HBsAg VLP vaccines provided similar protection profiles to the approved Pfizer mRNA vaccines used worldwide and may offer protection against SARS-CoV-2 VOC. IMPORTANCE Global COVID-19 vaccine distribution to low-income countries has been a major challenge of the pandemic. To address supply chain issues, RBD virus-like particle (VLP) vaccines that are cost-effective and capable of large-scale production were developed and evaluated for efficacy in preclinical mouse studies. We demonstrated that RBD-VLP vaccines protected K18-hACE2 mice against Alpha or Beta challenge similarly to Pfizer mRNA vaccination. Our findings showed that the VLP platform can be utilized to formulate immunogenic and efficacious COVID-19 vaccines.


Subject(s)
COVID-19 , Vaccines, Virus-Like Particle , Alum Compounds , Animals , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Emulsions , Hepatitis B Surface Antigens/genetics , Humans , Melphalan , Mice , Mice, Inbred BALB C , Pandemics , RNA, Messenger , RNA, Viral , SARS-CoV-2 , Squalene , Vaccines, Synthetic , Water , gamma-Globulins , mRNA Vaccines
15.
Int J Surg Open ; 43: 100491, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1930891

ABSTRACT

Introduction: Bronchial asthma is an age-old disease whereas COVID-19 is an officially declared pandemic on March 11, 2020 by WHO. Since both are primarily a disease of the respiratory system, researchers across the globe tried to explore the potential relationship between them; to date, there is no convincing data. Here, we tried to present a case to explore potential relationships between these two, if present. Case presentation: A 30-year-old male patient with well-controlled cough variant asthma was diagnosed with a case of covid-19 infection 12 months back. All other sign symptoms subsided except dry cough. The patient is treated with an inhaled bronchodilator, oral and inhaled steroid, Tab montelukast as well as other conservative management like hot water vapor, lozenge, honey, etc but symptoms were not controlled for the last 12 months. The patient could not do his job because of this problem. All examination and investigation findings were normal. After long-term use of inhaled steroids, he is now 50-60% improved and gradually improving. Discussion: Covid can exacerbate cough in an asthmatic patient. Neuronal activation and neuroinflammatory mechanisms may aggravate this cough after covid. Diagnosis confirmed clinically with the relevant improvement of symptoms. Other important differentials were excluded by appropriate history, examinations, and investigation. Cough is improved by steroids in this case. Conclusion: Summary of conclusion: Cough variant asthma may be aggravated with covid 19 infection and meticulous history, treatment, and follow up needed for an asthmatic patient who is infected with covid 19.

18.
Journal of Translational Critical Care Medicine ; 3(1):1-4, 2021.
Article in English | EuropePMC | ID: covidwho-1823802

ABSTRACT

It has been described that COVID-19 is a dynamic behavior and systemic affectation entity, so it is essential to develop the diagnostic and prognostic tools which allows to specifically identify target organ damage. The electrocardiographic finding of an inverse T-wave suggests transient apical dysfunction of the left ventricle, generating confusion among different heart diseases. However, despite the lack of troponin elevation and other myocardial injury signs, this finding is unspecific, especially in the patient with COVID-19. The aim of this manuscript is to present the case of a patient with COVID-19 without a previous diagnosis of heart disease, which manifests an isolated inverse T-wave.

19.
NPJ Vaccines ; 7(1): 36, 2022 Mar 14.
Article in English | MEDLINE | ID: covidwho-1740442

ABSTRACT

SARS-CoV-2 is a viral respiratory pathogen responsible for the current global pandemic and the disease that causes COVID-19. All current WHO approved COVID-19 vaccines are administered through the muscular route. We have developed a prototype two-dose vaccine (BReC-CoV-2) by combining the Receptor Binding Domain (RBD) antigen, via conjugation to Diphtheria toxoid (EcoCRM®). The vaccine is adjuvanted with Bacterial Enzymatic Combinatorial Chemistry (BECC), BECC470. Intranasal (IN) administration of BreC-CoV-2 in K18-hACE2 mice induced a strong systemic and localized immune response in the respiratory tissues which provided protection against the Washington strain of SARS-CoV-2. Protection provided after IN administration of BReC-CoV-2 was associated with decreased viral RNA copies in the lung, robust RBD IgA titers in the lung and nasal wash, and induction of broadly neutralizing antibodies in the serum. We also observed that BReC-CoV-2 vaccination administered using an intramuscular (IM) prime and IN boost protected mice from a lethal challenge dose of the Delta variant of SARS-CoV-2. IN administration of BReC-CoV-2 provided better protection than IM only administration to mice against lethal challenge dose of SARS-CoV-2. These data suggest that the IN route of vaccination induces localized immune responses that can better protect against SARS-CoV-2 than the IM route in the upper respiratory tract.

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