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1.
Artículo en Inglés | MEDLINE | ID: mdl-36103207

RESUMEN

BACKGROUND: Markers of a patient's social determinants of health, including healthcare insurance and median household income based on ZIP Code, have been associated with the interval between injury and ACL reconstruction (ACLR) as well as the presence of concomitant meniscus tears in children and adolescents. However, the aforementioned surrogate indicators of a patient's social determinants of health may not reflect all socioeconomic and healthcare resources affecting the care of ACL injuries in children and adolescents. The use of multivariate indices such as the Child Opportunity Index (COI) may help to better identify patients at risk for increased risk for delay between ACL injury and surgery, as well as the incidence of meniscus tears at the time of surgery. The COI is a summative measure of 29 indicators that reflect neighborhood opportunities across three domains: education, health and environment, and social and economic factors. COI scores range from 0 to 100 (100 being the highest possible score), as well as five categorical scores (very low, low, moderate, high, and very high) based on quintile rankings. QUESTIONS/PURPOSES: To investigate the relationship between neighborhood conditions and the treatment of ACL injuries in children and adolescents via the COI, we asked: (1) Is a lower COI score associated with a longer delay between ACL injury and surgery? (2) Does a higher proportion of patients with lower COI scores have meniscus tears at the time of ACLR? METHODS: In this retrospective, comparative study, we considered data from 565 patients, 18 years or younger, who underwent primary ACLR at an urban, tertiary children's hospital between 2011 and 2021. Of these patients, 5% (31 of 565) did not have a clearly documented date of injury, 2% (11 of 565) underwent revision reconstructions, and 1% (5 of 565) underwent intentionally delayed or staged procedures. Because we specifically sought to compare patients who had low or very low COI scores (lowest two quintiles) with those who had high or very high scores (highest two quintiles), we excluded 18% (103 of 565) of patients with moderate scores. Ultimately, 73% (415 of 565) of patients with COI scores in either the top or bottom two quintiles were included. Patient addresses at the time of surgery were used to determine the COI score. There were no differences between the groups in terms of gender. However, patients with high or very high COI scores had a lower median (IQR) age (15 years [2.6] versus 17 years [1.8]; p < 0.001) and BMI (23 kg/m2 [6.1] versus 25 kg/m2 [8.8]; p < 0.001), were more commonly privately insured (62% [117 of 188] versus 22% [51 of 227]; p < 0.001), and had a higher proportion of patients identifying as White (67% [126 of 188] versus 6.2% [14 of 227]; p < 0.001) compared with patients with low or very low COI scores. Medical records were reviewed for demographic, preoperative, and intraoperative data. Univariate analyses focused on the relationship of the COI and interval between injury and surgery, frequency of concomitant meniscus tears, and frequency of irreparable meniscus tears treated with partial meniscectomy. Multivariable regression analyses were used to determine factors that were independently associated with delayed surgery (longer than 60 and 90 days after injury), presence of concomitant meniscal injuries, and performance of meniscectomy. Multivariable models included insurance and race or ethnicity to determine whether COI was independently associative after accounting for these variables. RESULTS: Patients with a high or very high COI score had surgery earlier than those with a low or very low COI score (median [IQR] 53 days [53] versus 97 days [104]; p < 0.001). After adjusting for insurance and race/ethnicity, we found that patients with a low or very low COI score were more likely than patients with a high or very high COI score to have surgery more than 60 days after injury (OR 2.1 [95% CI 1.1 to 4.0]; p = 0.02) or more than 90 days after injury (OR 1.8 [95% CI 1.1 to 3.4]; p = 0.04). Furthermore, patients with low or very low COI scores were more likely to have concomitant meniscus tears (OR 1.6 [95% CI 1.1 to 2.5]; p = 0.04) compared with patients with high or very high COI scores. After controlling for insurance, race/ethnicity, time to surgery, and other variables, there was no association between COI and meniscectomy (OR 1.6 [95% CI 0.9 to 2.8]; p = 0.12) or presence of a chondral injury (OR 1.7 [95% CI 0.7 to 3.9]; p = 0.20). CONCLUSION: As the COI score is independently associated with a delay between ACL injury and surgery as well as the incidence of meniscus tears at the time of surgery, this score can be useful in identifying patients and communities at risk for disparate care after ACL injury. The COI score or similar metrics can be incorporated into medical records to identify at-risk patients and dedicate appropriate resources for efficient care. Additionally, neighborhoods with a low COI score may benefit from improvements in the availability of additional and/or improved resources. Future studies should focus on the relationship between the COI score and long-term patient-reported functional outcomes after ACL injury, identification of the specific timepoints in care that lead to delayed surgery for those with lower COI scores, and the impact of community-based interventions in improving health equity in children with ACL injury. LEVEL OF EVIDENCE: Level III, therapeutic study.

2.
STAR Protoc ; 3(4): 101719, 2022 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-36153732

RESUMEN

This protocol describes the use of silicon photonic microring resonator sensors for detection of Ebola virus (EBOV) and Sudan virus (SUDV) soluble glycoprotein (sGP). This protocol encompasses biosensor functionalization of silicon microring resonator chips, detection of protein biomarkers in sera, preparing calibration standards for analytical validation, and quantification of the results from these experiments. This protocol is readily adaptable toward other analytes, including cytokines, chemokines, nucleic acids, and viruses. For complete details on the use and execution of this protocol, please refer to Qavi et al. (2022).

3.
Artículo en Inglés | MEDLINE | ID: mdl-36073983

RESUMEN

BACKGROUND: Previous studies have investigated the impact of social determinants of health, such as the type of healthcare insurance and household income, on children and adolescents with ACL tears. However, despite the increasing incidence of ACL injury in young patients and a substantial proportion of families who may prefer languages other than English, the relationship between language and clinical care remains unclear. QUESTIONS/PURPOSES: To investigate the relationship between language and the care of children and adolescents with ACL tears, we asked: (1) Is a preferred language other than English (PLOE) associated with a delay between ACL injury and surgery? (2) Is a PLOE associated with a greater odds of a patient experiencing a meniscal tear and undergoing a meniscectomy than in those who prefer English? METHODS: We treated 591 patients surgically for ACL injuries between 2011 and 2021. Of those, we considered patients aged 18 years or younger who underwent primary ACL reconstruction for this retrospective, comparative study. Five percent (31 of 591) of patients were excluded because the date of injury was not clearly documented, 2% (11 of 591) were revision reconstructions, and 1% (6 of 591) underwent procedures that were intentionally delayed or staged, leaving 92% (543 of 591) for analysis. The mean age was 16 ± 2 years, and 51% (276 of 543) of patients were boys. The family's preferred language was noted, as were demographic data, time between injury and surgery, and intraoperative findings. A language other than English was preferred by 21% (113 of 543) of patients. Of these, 94% (106 of 113) preferred Spanish. In a univariate analysis, we used independent-samples t-tests, Mann-Whitney U-tests, and Fisher exact tests, as appropriate. Purposeful-entry multivariable regression analyses were used to determine whether PLOE was associated with increased time to surgery, concomitant meniscus injury, or performance of meniscectomy while adjusting for confounding variables. Variables were included in multivariable models if they met the threshold for statistical significance in univariate testing (p < 0.05). RESULTS: The median time between injury and ACL reconstruction was shorter in families who preferred English compared with those with a PLOE (69 days [IQR 80] versus 103 days [IQR 107)]; p < 0.001). After controlling for potentially confounding variables like insurance and age, we found that patients whose families had a PLOE had greater odds of undergoing surgery more than 60 days after injury (OR 2.2 [95% CI 1.3 to 3.8]; p = 0.005) and more than 90 days after injury (OR 1.8 [95% CI 1.1 to 2.8]; p = 0.02). After controlling for insurance, age, and other factors, PLOE was not associated with surgical delay beyond 180 days, concomitant meniscal tears, or performance of meniscectomy. CONCLUSION: In this study of children and adolescents undergoing primary ACL reconstruction, patients whose families prefer a language other than English experienced a longer delay between injury and surgery. In areas with a large proportion of families with a PLOE, partnerships with primary care clinicians, emergency departments, schools, athletic teams, and community organizations may improve efficiency in the care of children with ACL injuries. Clinicians proficient in other languages, reliable interpreter services, and translated references and resources may also be impactful. Our results suggest a need for further research on the experiences, needs, and long-term outcomes of these patients, as well as the association of preferred language with results after surgery. LEVEL OF EVIDENCE: Level III, therapeutic study.

4.
Arthrosc Sports Med Rehabil ; 4(4): e1575-e1579, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36033169

RESUMEN

Purpose: To evaluate the quality and correlation of readability on actionability and understandability of shoulder arthroscopy-related patient education materials (PEMs) found via a routine Google search. Methods: Two independent authors performed an online Google search with the term "shoulder arthroscopy." The first 5 pages of search results were then screened for PEMs. Journal articles, news articles, nontext materials, and unrelated websites were excluded. The readability of included resources was calculated using objective metrics: Flesch-Kincaid Grade Score, Simple Measure of Gobbledygook index, Coleman-Liau Index, and the Gunning Fog Index. Patient Education Material Assessment Tool for Printed Materials assessed for understandability and actionability. Associations between readability and actionability and understandability were determined using Spearman correlation and linear regression. Results: The searches returned 53 websites related to shoulder arthroscopy. A total of 34 (64%) met inclusion criteria. A high school reading level or greater was required to read the average PEM according to all scales used. The average PEM received a Patient Education Material Assessment Tool for Printed Materials score of 61.33 in understandability (range 18.75-89.47) and 55.59 points in actionability (range 16.67-83.33). An easily understood or actionable article would score at least 70 points. A moderate correlation was observed between readability and actionability on three of the scales used (r = 0.5, r = 0.59, r = 0.61). Conclusions: Most shoulder arthroscopy PEMs identified on Google are not written at a level that the average patient can read, understand, or act on (actionability). Clinical Relevance: Orthopaedic surgeons should be aware of the resources that patients use to obtain medical information. More accessible PEMs should be developed for patients undergoing shoulder arthroscopy to enhance comprehension of their condition and improve shared decision-making.

5.
Arthrosc Sports Med Rehabil ; 4(4): e1539-e1544, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36033192

RESUMEN

Purpose: To obtain a quantifiable measure of the frequency with which a shoulder instability article is discussed online and the association with its corresponding bibliometric impact, based on the Scopus Cite Score (SCS) or Web of Science Impact Factor (WSIF). Methods: The top 100 most-mentioned articles on shoulder instability based on Altmetric Attention Score (AAS) were extracted from the Altmetric Database. Mentions within blogs, news articles and outlets, public policy, and social media platforms, such as Twitter and Facebook, were included. Study impact was assessed using SCS or WSIF. The degree of association between AAS and impact was determined using Spearman correlation, logarithmic regression, and multivariate regression. Results: The most common study designs were "Clinical Trial," with 52 articles (49.5%), "Systematic Review" with 16 articles (15.2%), and "Review" with 10 articles (9.5%). Twitter provided more online mentions than other platforms, with the average article being discussed 27.7 times (range 0-220 times). A significant positive effect (estimate = 2.616, P = .0075) was observed between the AAS and WSIF, based on the logarithmic regression. Multivariate regression revealed that blogs help raise both WSIF and SCS (estimate = 7.272, P < .05). Conclusions: Social media and other online platforms are a strong way to disseminate information to patients. A positive association was observed between overall online attention and the bibliometric impact of an article related to shoulder instability. Clinical trials related to shoulder instability that receive online mentions, especially discussion in blogs, are more likely to be cited in the future than their counterparts. Clinical Relevance: The results of our study can guide authors as they aim to disseminate their articles. Twitter may be used as a tool to reach patients who may not venture into academic journals with current peer-reviewed articles. Further, blogs may be used to reach academic audiences and raise bibliometric impact broadly.

6.
ACS Infect Dis ; 8(8): 1468-1479, 2022 08 12.
Artículo en Inglés | MEDLINE | ID: mdl-35867632

RESUMEN

Serological testing for acute infection or prior exposure is critical for patient management and coordination of public health decisions during outbreaks. Current methods have several limitations, including variable performance, relatively low analytical and clinical sensitivity, and poor detection due to antigenic drift. Serological methods for SARS-CoV-2 detection for the ongoing COVID-19 pandemic suffer from several of these limitations and serves as a reminder of the critical need for new technologies. Here, we describe the use of ultrabright fluorescent reagents, Plasmonic Fluors, coupled with antigen arrays that address a subset of these limitations. We demonstrate its application using patient samples in SARS-CoV-2 serological assays. In our multiplexed assay, SARS-CoV-2 antigens were spotted into 48-plex arrays within a single well of a 96-well plate and used to evaluate remnant laboratory samples of SARS-CoV-2 positive patients. Signal-readout was performed with Auragent Bioscience's Empower microplate reader, and microarray analysis software. Sample volumes of 1 µL were used. High sensitivity of the Plasmonic Fluors combined with the array format enabled us to profile patient serological response to eight distinct SARS-CoV-2 antigens and evaluate responses to IgG, IgM, and IgA. Sensitivities for SARS-CoV-2 antigens during the symptomatic state ranged between 72.5 and 95.0%, specificity between 62.5 and 100%, and the resulting area under the curve values between 0.76 and 0.97. Together, these results highlight the increased sensitivity for low sample volumes and multiplex capability. These characteristics make Plasmonic Fluor-enhanced antigen arrays an attractive technology for serological studies for the COVID-19 pandemic and beyond.


Asunto(s)
COVID-19 , SARS-CoV-2 , Anticuerpos Antivirales , COVID-19/diagnóstico , Prueba de COVID-19 , Técnicas de Laboratorio Clínico/métodos , Humanos , Pandemias , Sensibilidad y Especificidad
7.
Expert Opin Drug Metab Toxicol ; 18(5): 313-322, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35818714

RESUMEN

INTRODUCTION: Oral administration of cannabinoids is a convenient route of administration in many cases. To enhance the poor and variable bioavailability of cannabinoids, selected strategies utilizing proper delivery systems have been designed. Low solubility in the GI aqueous media is the first and most critical barrier. Thereafter, cannabinoids can reach the systemic blood circulation via the portal vein that is associated with significant hepatic first pass metabolism (FPM) or bypass it via lymphatic absorption. AREAS COVERED: The solubility obstacle of cannabinoids is mainly addressed with lipid-based formulations such as self-nanoemulsifying drug delivery systems (SNEDDS). Certain lipids are used to overcome the solubility issue. Surfactants and other additives in the formulation have additional impact on several barriers, including dictating the degree of lymphatic bioavailability and hepatic FPM. Gastro-retentive formulation is also plausible. EXPERT OPINION: Comparison of the role of the same SNEDDS formulation, cyclosporine vs. cannabinoids, when used to elevate the oral bioavailability of different compounds, is presented. It illustrates some similarities and major mechanistic differences obtained by the same SNEDDS. Thus, the different influence over the absorption pathway illuminates the importance of understanding the absorption mechanism and its barriers to properly select appropriate strategies to achieve enhanced oral bioavailability.


Asunto(s)
Cannabinoides , Nanopartículas , Administración Oral , Disponibilidad Biológica , Sistemas de Liberación de Medicamentos , Emulsiones , Humanos , Tamaño de la Partícula , Solubilidad
8.
Biomacromolecules ; 23(8): 3417-3428, 2022 08 08.
Artículo en Inglés | MEDLINE | ID: mdl-35881559

RESUMEN

The alternating architecture and hydrophobic side chains hinder hydrolytic cleavage and anhydride interchange in poly(sebacic acid-ricinoleic acid) (P(SA-RA)), which provides stable polyanhydrides at room temperature. In this report, a series of polyanhydrides were designed to investigate the effect of ester bonds, hydrophobic side chains, phenyl moieties, and their distance from anhydride bonds on their stability and properties. Polyanhydrides with alternating architecture are constructed by the polymerization of ester-diacids prepared from ricinoleic or other hydroxy acids with anhydrides such as succinic, maleic, and phthalic anhydrides. The hydrophobic side chains are designed closer to anhydride bonds to investigate hindrance to hydrolytic cleavage and anhydride interchange. Polyanhydrides were obtained by the activation of ester-diacid using acetic anhydride followed by melt condensation. The reactions were monitored by NMR, Fourier transform infrared (FTIR), and gel permeation chromatography (GPC). The synthesized poly(ester-anhydride)s with a shorter chain length compared to P(SA-RA) were stable at room temperature. The hydrolytic degradation studies reveal that the phenyl moiety present in poly(ricinoleic acid phthalate) (PRAP) and poly(hydroxystearic acid phthalate) (PHSAP) reduces the hydrolysis of anhydride bonds. Poly(hydroxyoctanoic acid succinate) (PHOAS) demonstrates the highest molecular weight of all tested polymers. The results reveal that the presence of hydrophobic side chains, phenyl moieties, and their distance from anhydride bonds significantly improves the stability. These stable polyanhydrides can provide convenience to use in control drug-delivery applications. The in vitro drug release study using ibuprofen shows that polymers with aromatic units such as PRAP and PHSAP establish sustained release, which presents more than 50 and 40% of ibuprofen over a period of 28 days.


Asunto(s)
Anhídridos , Polianhídridos , Anhídridos/química , Ésteres/química , Hidroxiácidos , Ibuprofeno , Ácidos Ricinoleicos/química
9.
Med J Malaysia ; 77(Suppl 1): 45-52, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35899889

RESUMEN

INTRODUCTION: We investigated the impact of Coronavirus Disease 2019 (COVID-19) pandemic on urological services by analyzing current attitudes and practices of urologists in the Southeast Asian (SEA) countries and create ways for improvement. MATERIALS AND METHODS: Quantitative data were used as critical indicators of workload of urological services from each country in SEA. Qualitative data analysis was done to describe the current state of attitudes of urologists against COVID-19 in the region. A strengths, weaknesses, opportunities, and threats (SWOT) analysis was performed to formulate strategic action plans. RESULTS: A total of seven urologists from six SEA countries completed the survey. Approximately 21-40% reduction in elective surgeries and outpatient visits, as stated by 42.9% and 57.1% of respondents, respectively was noted. Collectively, most respondents (71.4%) experienced <20% reduction in emergency visits. Various strategies were utilized as reaction to the pandemic. These include utilization of virtual communication platforms, pre-surgical COVID-19 screening, and limited number of accepted outpatient appointments and surgeries. Face to face patient consultations were still considered needed by many urologists although most countries had prohibited direct patient contact. The national response of countries such as Malaysia, Singapore, Thailand, and Vietnam were successful in controlling the pandemic. However, Indonesia and Philippines struggled because of the limited testing and tracing capabilities. Through the SWOT analysis, strategies were identified which can help overcome COVID-19 and any other future pandemics: (1) restarting the urological services in a safe and sustainable manner; (2) optimizing financial and infrastructural capacities; and (3) regional collaboration to strengthen the health systems. CONCLUSION: COVID-19 negatively impacted many health aspects, especially the delivery of urological services in SEA. Therefore, to ensure sustainability of urological services during the pandemic crisis, health care system should focus on safe, resilient, and adaptive approach with regional collaboration.


Asunto(s)
COVID-19 , Adaptación Psicológica , Asia Sudoriental , COVID-19/epidemiología , Humanos , Pandemias/prevención & control , SARS-CoV-2
10.
Pharmaceutics ; 14(7)2022 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-35890298

RESUMEN

Polyanhydrides have been synthesized for decades by melt-polycondensation of diacid monomers and 5 to >10 times mole excess acetic anhydride to diacid monomers to form polymers with a polydispersity ranging from 2.5 to 6 and low reproducibility. Hydrophobic segments in polyanhydrides are beneficial to hinder the characteristic hydrolytic cleavage of an anhydride bond that provides stable polyanhydrides at room temperature. The objective of this work is to synthesize aliphatic polyanhydrides with various hydrophobic segments, controllable and reproducible molecular weight, and low polydispersity that are essential for potential use as drug carriers. A series of polyanhydrides of suberic, azelaic, sebacic, and dodecanedioic acids with controlled molecular weight, reduced polydispersity, and standard deviation of molecular weights, have been synthesized. All synthesized polyanhydrides were thoroughly characterized by NMR, Fourier transform infrared spectroscopy, and gel permeation chromatography. Molecular weights of the synthesized polyanhydrides are highly controllable, depending on the degree of activation of the dicarboxylic acid monomers, i.e., the amount of acetic anhydride used during synthesis. Polyanhydrides have been synthesized in triplicate by melt-polycondensation, using various mole ratios of acetic anhydride to diacids. The standard deviation of the molecular weights of the polyanhydrides is minute when using 1 equivalent of acetic anhydride during the activation of dicarboxylic acids, whereas if excess acetic anhydride is used, the standard deviation is very high. The effect of safe and natural inorganic catalysts, Calcium oxide, Zinc oxide, and Calcium carbonate on polymerization is also studied. As-synthesized poly(sebacic acid) can offer convenience to use in controlled drug delivery applications. In vitro drug release study using Temozolamide (TMZ), a medication used to treat brain tumors such as glioblastoma and anaplastic astrocytoma, shows 14% TMZ release after the first hour and 70% release over one day from the poly(sebacic acid) wafers.

11.
Cell Rep Methods ; 2(6): 100234, 2022 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-35784644

RESUMEN

Ebola virus (EBOV) is a highly infectious pathogen, with a case mortality rate as high as 89%. Rapid therapeutic treatments and supportive measures can drastically improve patient outcome; however, the symptoms of EBOV disease (EVD) lack specificity from other endemic diseases. Given the high mortality and significant symptom overlap, there is a critical need for sensitive, rapid diagnostics for EVD. Facile diagnosis of EVD remains a challenge. Here, we describe a rapid and sensitive diagnostic for EVD through microring resonator sensors in conjunction with a unique biomarker of EBOV infection, soluble glycoprotein (sGP). Microring resonator sensors detected sGP in under 40 min with a limit of detection (LOD) as low as 1.00 ng/mL in serum. Furthermore, we validated our assay with the detection of sGP in serum from EBOV-infected non-human primates. Our results demonstrate the utility of a high-sensitivity diagnostic platform for detection of sGP for diagnosis of EVD.

12.
Plant Mol Biol ; 109(4-5): 351-353, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35727520
14.
Cancers (Basel) ; 14(12)2022 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-35740544

RESUMEN

While the role of proton therapy in gastric cancer is marginal, its role in esophageal and anorectal cancers is expanding. In esophageal cancer, protons are superior in sparing the organs at risk, as shown by multiple dosimetric studies. Literature is conflicting regarding clinical significance, but the preponderance of evidence suggests that protons yield similar or improved oncologic outcomes to photons at a decreased toxicity cost. Similarly, protons have improved sparing of the organs at risk in anorectal cancers, but clinical data is much more limited to date, and toxicity benefits have not yet been shown clinically. Large, randomized trials are currently underway for both disease sites.

15.
Methods Mol Biol ; 2492: 53-72, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35733038

RESUMEN

The blood-brain barrier (BBB) is a component of the neurovascular unit formed by specialized brain microvascular endothelial cells surrounded by astrocytes end-feet processes, pericytes, and a basement membrane. The BBB plays an important role in the maintenance of brain homeostasis and has seen a growing involvement in the pathophysiology of various neurological diseases. On the other hand, the presence of such a barrier remains an important challenge for drug delivery to treat such illnesses.Since the pioneering work describing the isolation and cultivation of primary brain microvascular cells about 50 years ago until now, the development of an in vitro model of the BBB that is scalable, capable to form tight monolayers, and predictive of drug permeability in vivo remained extremely challenging.The recent description of the use of induced pluripotent stem cells (iPSCs) as a modeling tool for neurological diseases raised momentum into the use of such cells to develop new in vitro models of the BBB. This chapter will provide an exhaustive description of the use of iPSCs as a source of cells for modeling the BBB in vitro, describe the advantages and limitations of such model, as well as describe their prospective use for disease modeling and drug permeability screening platforms.


Asunto(s)
Barrera Hematoencefálica , Células Madre Pluripotentes Inducidas , Barrera Hematoencefálica/fisiología , Células Endoteliales/fisiología , Humanos , Células Madre Pluripotentes Inducidas/fisiología , Pericitos , Estudios Prospectivos
16.
BMC Infect Dis ; 22(1): 559, 2022 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-35725387

RESUMEN

BACKGROUND: There is still a paucity of evidence on the outcomes of coronavirus disease 2019 (COVID-19) among people living with human immunodeficiency virus (PWH) and those co-infected with tuberculosis (TB), particularly in areas where these conditions are common. We describe the clinical features, laboratory findings and outcome of hospitalised PWH and human immunodeficiency virus (HIV)-uninfected COVID-19 patients as well as those co-infected with tuberculosis (TB). METHODS: We conducted a multicentre cohort study across three hospitals in Cape Town, South Africa. All adults requiring hospitalisation with confirmed COVID-19 pneumonia from March to July 2020 were analysed. RESULTS: PWH comprised 270 (19%) of 1434 admissions. There were 47 patients with active tuberculosis (3.3%), of whom 29 (62%) were PWH. Three-hundred and seventy-three patients (26%) died. The mortality in PWH (n = 71, 26%) and HIV-uninfected patients (n = 296, 25%) was comparable. In patients with TB, PWH had a higher mortality than HIV-uninfected patients (n = 11, 38% vs n = 3, 20%; p = 0.001). In multivariable survival analysis a higher risk of death was associated with older age (Adjusted Hazard Ratio (AHR) 1.03 95%CI 1.02-1.03, p < 0.001), male sex (AHR1.38 (95%CI 1.12-1.72, p = 0.003) and being "overweight or obese" (AHR 1.30 95%CI 1.03-1.61 p = 0.024). HIV (AHR 1.28 95%CI 0.95-1.72, p 0.11) and active TB (AHR 1.50 95%CI 0.84-2.67, p = 0.17) were not independently associated with increased risk of COVID-19 death. Risk factors for inpatient mortality in PWH included CD4 cell count < 200 cells/mm3, higher admission oxygen requirements, absolute white cell counts, neutrophil/lymphocyte ratios, C-reactive protein, and creatinine levels. CONCLUSION: In a population with high prevalence of HIV and TB, being overweight/obese was associated with increased risk of mortality in COVID-19 hospital admissions, emphasising the need for public health interventions in this patient population.


Asunto(s)
COVID-19 , Infecciones por VIH , Tuberculosis , Adulto , COVID-19/epidemiología , Estudios de Cohortes , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Hospitalización , Humanos , Masculino , Obesidad/complicaciones , Sobrepeso , Prevalencia , Sudáfrica/epidemiología , Tuberculosis/complicaciones , Tuberculosis/epidemiología
17.
Mol Brain ; 15(1): 42, 2022 05 09.
Artículo en Inglés | MEDLINE | ID: mdl-35534865

RESUMEN

Neuropeptides act mostly on a class of G-protein coupled receptors, and play a fundamental role in the functions of neural circuits underlying behaviors. However, physiological functions of some neuropeptide receptors are poorly understood. Here, we used the molluscan model system Aplysia and microinjected the exogenous neuropeptide receptor apATRPR (Aplysia allatotropin-related peptide receptor) with an expression vector (pNEX3) into Aplysia neurons that did not express the receptor endogenously. Physiological experiments demonstrated that apATRPR could mediate the excitability increase induced by its ligand, apATRP (Aplysia allatotropin-related peptide), in the Aplysia neurons that now express the receptor. This study provides a definitive evidence for a physiological function of a neuropeptide receptor in molluscan animals.


Asunto(s)
Aplysia , Neuropéptidos , Animales , Aplysia/fisiología , Hormonas de Insectos , Neuronas/metabolismo , Neuropéptidos/metabolismo , Receptores de Neuropéptido/metabolismo
18.
J Colloid Interface Sci ; 622: 904-913, 2022 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-35561610

RESUMEN

It is always a challenge to encapsulate water-soluble peptides in polymer nanoparticle (NP) systems. We establish and validate our newly developed non-aqueous nanoprecipitation method to encapsulate neuro-peptides drugs such as oxytocin and Luteinizing hormone-releasing hormone (LHRH) in poly(sebacic anhydride) (PSA) NPs. NPs were prepared by a solvent-antisolvent process under a strict anhydrous environment to obtain high drug loading and to avoid premature PSA degradation and drug release. Dynamic light scattering (DLS) and Scanning Electron Microscopy (SEM) reveal the size for both drug loaded PSA NPs to âˆ¼ 300 nm. The drug loaded NPs were dispersible and spherical in shape with uniform morphology. The in vitro release profile of oxytocin from PSA NPs occurs with the burst release of âˆ¼ 50% within the first hour in the aqueous release medium, whereas LHRH release is comparatively slow. Thus, looking into the fast degrading properties of PSA and drug release behavior, the developed NPs can be used for direct delivery of the neuropeptides to the olfactory epithelium using a refillable nasal atomizer that deposits mist onto the olfactory neuro-epithelium. We also applied our developed method to prepare NPs of poly(lactic-co-glycolic acid) (PLGA), polylactic acid (PLA), and poly(ε-caprolactone) (PCL). A Thyrotropin releasing hormone (TRH) was used as the sample neuropeptide drug to validate our non-aqueous method. The results reveal the formation of TRH loaded PLGA, PLA and PCL NPs with 100% drug loading. TEM analysis shows the formation of spherical NPs, having similar release properties as those of PSA NPs. Overall, we report that our developed method is suitable for co-encapsulating hydrophilic drugs in polymer NPs with high drug loading and release properties.


Asunto(s)
Nanopartículas , Oxitocina , Portadores de Fármacos/química , Hormona Liberadora de Gonadotropina , Nanopartículas/química , Tamaño de la Partícula , Poliésteres/química , Polímeros
19.
Int J Pharm ; 621: 121797, 2022 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-35525470

RESUMEN

While Pickering emulsions have been known since 1906, where oil droplets are dispersed in aqueous media owing to nanoparticles decorating each oil droplet, no solid lipid microparticles decorated with nanoparticles have been described. These Solid-Pickering microparticles are surfactant-free micro-scale spherical active agent carriers composed of beeswax as a natural solid lipid with chitosan and starch nanoparticles embedded in the surface. Microparticles of this type were made by dispersing molten lipid in hot aqueous media containing dispersed nanoparticles to create microdroplets. Once the droplets are cooled below the melting point of the lipid, the microparticles of spherical form are obtained. The novel system allows encapsulation of active agents within a solid lipid core which is slowly released over time. It has been demonstrated through encapsulation of Ibuprofen and Lidocaine as a model poorly water-soluble drugs and an extended-release profile (for at least a week) was achieved. These Solid Pickering microparticles can be used in food, medicine, agriculture, and personal care products.


Asunto(s)
Portadores de Fármacos , Nanopartículas , Emulsiones , Lípidos , Microesferas , Tamaño de la Partícula , Agua
20.
FASEB J ; 36 Suppl 12022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35560704

RESUMEN

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). The portal of entry for the virus is peptidase ACE2, a major key player of the renin-angiotensin-aldosterone system (RAAS), resulting in severe lung injury. Although COVID-19 mainly manifests as an acute respiratory distress syndrome (ARDS), there is increasing evidence of neurological symptoms in patients infected by COVID-19. Yet, there is limited understanding of how COVID-19 impacts the central nervous system (CNS). We speculate that such neurological symptoms maybe a consequence of a dysfunction of the blood-brain barrier (BBB) with our central hypothesis that the neurological effects of SARS CoV-2 are driven by chronic hypoxic stress-impaired ACE2 at the BBB. METHODS: An in-vitro human induced pluripotent stem cells (hiPSCs) BBB model was used in the study. Such model was exposed to various levels of hypoxia (1,5 and 10%) for up to 24 hours. In addition, normoxic cells were treated with Angiotensin II (AngII) or Angiotensin 1-7 (degradation by product of AngII by ACE2). Changes in the barrier function was assessed using TEER, permeability to fluorescein and tight junction staining. Changes in ACE2 and MasR expression was assessed by immunofluorescence, whereas ACE2 shedding and HIF-1 alpha expression was assessed by ELISA. RESULTS: Mild (10%) hypoxia was sufficient to induce the loss of barrier function. Secretion of ACE2 under hypoxia followed a biphasic pattern, with highest levels at 5% and 10%. Ang II and Ang1-7 had little effect on the barrier function under normoxic condition. The hypoxic exposure induced shedding of the membrane bound ACE2 and molecular mechanism of hypoxic exposure in regulation of ACE2 occurs in a HIF1α- dependent manner. DISCUSSION: Our preliminary data suggest that our human model of the BBB responds to hypoxia and express critical components of RAAS. Both ACE2 and MasR negatively respond to mild hypoxia followed by a decreased barrier function with no changes in tight junction complex. Such loss was correlated with increased ACE2 shedding in HIF1α- dependent manner. We are currently investigating role of Ang 1-7 in rescuing barrier function under hypoxic stress.

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