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1.
J Vis ; 23(10): 7, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37695612

RESUMO

Visual confidence generally depends on performance in targeted perceptual tasks. However, it remains unclear how factors unrelated to performance affect confidence. Given the hierarchical nature of visual processing, both local and global stimulus features can influence confidence, but their strengths of influence remain unknown. To address this question, we independently manipulated the local contrast signals and the global coherence signals in a multiple-aperture motion pattern. The drifting-Gabor elements were individually manipulated to give rise to a coherent global motion percept. In both dichotomous direction-discrimination task (Experiment 1) and analog direction-judgment task (Experiment 2), we found stimulus-dependent biases in metacognition despite matched perceptual performance. Specifically, participants systematically gave higher confidence ratings to an incoherent pattern with clear elements (i.e., strong local but weak global signals) than a coherent pattern with noisy elements (i.e., weak local but strong global signals). We did not find any systematic effects of local/global stimulus features on metacognitive sensitivity. Model comparisons show that variation in local/global signals in the stimulus should be considered a factor influencing confidence, even after controlling for the effects of performance. Our results suggest that the metacognitive system, when generating confidence for a perceptual task, puts more weights on local than global signals.


Assuntos
Metacognição , Humanos , Viés , Julgamento , Movimento (Física) , Percepção Visual
2.
J Bacteriol ; 204(10): e0026922, 2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36106854

RESUMO

Staphylococcus aureus chronically colonizes up to 30% of the human population on the skin or mucous membranes, including the nasal tract or vaginal canal. While colonization is often benign, this bacterium also has the capability to cause serious infections. Menstrual toxic shock syndrome (mTSS) is a serious toxinosis associated with improper use of tampons, which can induce an environment that is favorable to the production of the superantigen known as toxic shock syndrome toxin-1 (TSST-1). To better understand environmental signaling that influences TSST-1 production, we analyzed expression in the prototype mTSS strain S. aureus MN8. Using transcriptional and protein-based analysis in two niche-related media, we observed that TSST-1 expression was significantly higher in synthetic nasal medium (SNM) than in vaginally defined medium (VDM). One major divergence in medium composition was high glucose concentration in VDM. The glucose-dependent virulence regulator gene ccpA was deleted in MN8, and, compared with wild-type MN8, we observed increased TSST-1 expression in the ΔccpA mutant when grown in VDM, suggesting that TSST-1 is repressed by catabolite control protein A (CcpA) in the vaginal environment. We were able to relieve CcpA-mediated repression by modifying the glucose level in vaginal conditions, confirming that changes in nutritional conditions contribute to the overexpression of TSST-1 that can lead to mTSS. We also compared CcpA-mediated repression to other key regulators of tst, finding that CcpA regulation is dominant compared to other characterized regulatory mechanisms. This study underlines the importance of environmental signaling for S. aureus pathogenesis in the context of mTSS. IMPORTANCE Menstrual toxic shock syndrome (mTSS) is caused by strains of Staphylococcus aureus that overproduce a toxin known as toxic shock syndrome toxin-1 (TSST-1). This work studied how glucose levels in a model vaginal environment could influence the amount of TSST-1 that is produced by S. aureus. We found that high levels of glucose repress TSST-1 production, and this is done by a regulatory protein called catabolite control protein A (CcpA). The research also demonstrated that, compared with other regulatory proteins, the CcpA regulator appears to be the most important for maintaining low levels of TSST-1 in the vaginal environment, and this information helps to understand how changes in the vaginal environmental can lead to mTSS.


Assuntos
Choque Séptico , Infecções Estafilocócicas , Feminino , Humanos , Staphylococcus aureus/metabolismo , Proteína Estafilocócica A/metabolismo , Choque Séptico/microbiologia , Glucose/metabolismo , Superantígenos/genética , Superantígenos/metabolismo , Enterotoxinas/genética , Enterotoxinas/metabolismo , Infecções Estafilocócicas/microbiologia , Meios de Cultura
3.
Int J Mol Sci ; 23(24)2022 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-36555852

RESUMO

Bexarotene is an FDA-approved drug for the treatment of cutaneous T-cell lymphoma (CTCL); however, its use provokes or disrupts other retinoid-X-receptor (RXR)-dependent nuclear receptor pathways and thereby incites side effects including hypothyroidism and raised triglycerides. Two novel bexarotene analogs, as well as three unique CD3254 analogs and thirteen novel NEt-TMN analogs, were synthesized and characterized for their ability to induce RXR agonism in comparison to bexarotene (1). Several analogs in all three groups possessed an isochroman ring substitution for the bexarotene aliphatic group. Analogs were modeled for RXR binding affinity, and EC50 as well as IC50 values were established for all analogs in a KMT2A-MLLT3 leukemia cell line. All analogs were assessed for liver-X-receptor (LXR) activity in an LXRE system to gauge the potential for the compounds to provoke raised triglycerides by increasing LXR activity, as well as to drive LXRE-mediated transcription of brain ApoE expression as a marker for potential therapeutic use in neurodegenerative disorders. Preliminary results suggest these compounds display a broad spectrum of off-target activities. However, many of the novel compounds were observed to be more potent than 1. While some RXR agonists cross-signal the retinoic acid receptor (RAR), many of the rexinoids in this work displayed reduced RAR activity. The isochroman group did not appear to substantially reduce RXR activity on its own. The results of this study reveal that modifying potent, selective rexinoids like bexarotene, CD3254, and NEt-TMN can provide rexinoids with increased RXR selectivity, decreased potential for cross-signaling, and improved anti-proliferative characteristics in leukemia models compared to 1.


Assuntos
Leucemia , Linfoma Cutâneo de Células T , Neoplasias Cutâneas , Humanos , Bexaroteno/farmacologia , Receptores X de Retinoides/metabolismo , Tetra-Hidronaftalenos/farmacologia , Receptores X do Fígado , Retinoides/farmacologia , Triglicerídeos
4.
Surg Endosc ; 35(4): 1566-1571, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32246234

RESUMO

BACKGROUND: The Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) tracks 30-day outcomes of bariatric patients, but only at accredited centers. Presently, these cases are not broken down by state. Administrative databases can be used to answer some of the questions that are not asked by clinical databases and also to validate those databases. We proposed using the inpatient and outpatient administrative databases in Texas to examine both the numbers and trends of bariatric surgery in Texas over a 5-year period. METHODS: The Texas Inpatient Public Use Data File (IPUDF) and the Texas Outpatient Public Data File (OPUDF) were examined for the years 2013-2017. We searched for patients undergoing laparoscopic adjustable gastric banding (LAGB), sleeve gastrectomy (SG), laparoscopic Roux-en-Y gastric bypass (LRYGB) and duodenal switch. Robotic assisted cases were also examined. RESULTS: There were 105,199 bariatric cases performed in Texas from 2013 to 2017. There were 173 centers performing bariatric surgery. The most common operation performed was the sleeve gastrectomy at 73,663 case (70% of total). Gastric bypasses were second at 22,890 cases. During this time period, LAGB almost disappeared; dropping from 2090 cases in 2013 to 115 cases in 2017, with removal of 2097 LAGB in the study period in the OPUDF. During this time period, there was a lower growth rate of the number of SG in the IPUDF with a large increase in SG performed with outpatient status, while LRYGB remained relatively stable. CONCLUSION: Rates of bariatric surgery in Texas are increasing slowly. The dominant procedure is the SG with a trend towards being done under outpatient status. LAGB has been essentially phased out. There is an increase in SG being performed under 'outpatient' status.


Assuntos
Derivação Gástrica/métodos , Bases de Dados Factuais , Feminino , História do Século XXI , Humanos , Masculino , Texas
5.
Theor Popul Biol ; 135: 49-55, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32888942

RESUMO

The order Hymenoptera includes most of the eusocial species on the planet. Correlated is the fact that many of the social species within the order are haplodiploid and use complementary sex determination (CSD) to determine the sex of offspring. CSD is the mechanism by why single sex alleles within an organism result in male development (haploid) and mismatched sex alleles develop into females (diploids). Related to this is the production of diploid males: fertilized eggs with matched sex alleles which develop as male instead of female. Honey bees are no exception to this, and as their numbers continue to suffer globally and their genetic diversity lowers, the effects of diploid male production (DMP) may pose an increased risk to the survival of bee colonies. In the present study, we develop a model for diploid male production in a honey bee colony and show that with ample resources, this phenomena has little effect on a colony's health, but there is a limit to the sustainability of a colony suffering from diploid male production. We use our model to show that there were likely no great evolutionary pressures against CSD and DMP in wild honey bees as its effects on colony health in the wild would have been negligible but increased environmental hazards such as pesticides and monoculture crops increase the effects of DMP on colony health.


Assuntos
Diploide , Processos de Determinação Sexual , Alelos , Animais , Abelhas/genética , Feminino , Haploidia , Masculino , Processos de Determinação Sexual/genética
6.
Am J Physiol Cell Physiol ; 317(5): C1011-C1024, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31433691

RESUMO

Unaccustomed resistance exercise can initiate skeletal muscle remodeling and adaptive mechanisms that can confer protection from damage and enhanced strength with subsequent stimulation. The myofiber may provide the primary origin for adaptation, yet multiple mononuclear cell types within the surrounding connective tissue may also contribute. The purpose of this study was to evaluate the acute response of muscle-resident interstitial cells to contraction initiated by electrical stimulation (e-stim) and subsequently determine the contribution of pericytes to remodeling as a result of training. Mice were subjected to bilateral e-stim or sham treatment. Following a single session of e-stim, NG2+CD45-CD31- (NG2+Lin-) pericyte, CD146+Lin- pericyte, and PDGFRα+ fibroadipogenic progenitor cell quantity and function were evaluated via multiplex flow cytometry and targeted quantitative PCR. Relative quantity was not significantly altered 24 h postcontraction, yet unique gene signatures were observed for each cell population at 3 h postcontraction. CD146+Lin- pericytes appeared to be most responsive to contraction, and upregulation of genes related to immunomodulation and extracellular matrix remodeling was observed via RNA sequencing. Intramuscular injection of CD146+Lin- pericytes did not significantly increase myofiber size yet enhanced ECM remodeling and angiogenesis in response to repeated bouts of e-stim for 4 wk. The results from this study provide the first evidence that CD146+Lin- pericytes are responsive to skeletal muscle contraction and may contribute to the beneficial outcomes associated with exercise.


Assuntos
Contração Muscular/fisiologia , Músculo Esquelético/citologia , Músculo Esquelético/fisiologia , Pericitos/metabolismo , Animais , Antígeno CD146/metabolismo , Diferenciação Celular/fisiologia , Linhagem da Célula/fisiologia , Estimulação Elétrica/métodos , Masculino , Camundongos , Camundongos Endogâmicos C57BL
7.
Biol Pharm Bull ; 42(4): 607-616, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30930420

RESUMO

Liver regeneration is a very complex process and is regulated by several cytokines and growth factors. It is also known that liver transplantation and the regeneration process cause massive oxidative stress, which interferes with liver regeneration. The placenta is known to contain various physiologically active ingredients such as cytokines, growth factors, and amino acids. In particular, human placenta hydrolysate (hPH) has been found to contain many amino acids. Most of the growth factors found in the placenta are known to be closely related to liver regeneration. Therefore, in this study, we investigated whether hPH is effective in promoting liver regeneration in rats undergoing partial hepatectomy. We confirmed that cell proliferation was significantly increased in HepG2 and human primary cells. Hepatocyte proliferation was also promoted in partial hepatectomized rats by hPH treatment. hPH increased liver regeneration rate, double nucleic cell ratio, mitotic cell ratio, proliferating cell nuclear antigen (PCNA), and Ki-67 positive cells in vivo as well as interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), and hepatocyte growth factor (HGF). Moreover, Kupffer cells secreting IL-6 and TNF-α were activated by hPH treatment. In addition, hPH reduced thiobarbituric acid reactive substances (TBARs) and significantly increased glutathione (GSH), glutathione peroxidase (GPx), and superoxide dismutase (SOD). Taken together, these results suggest that hPH promotes liver regeneration by activating cytokines and growth factors associated with liver regeneration and eliminating oxidative stress.


Assuntos
Antioxidantes/fisiologia , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Regeneração Hepática , Placenta , Animais , Linhagem Celular , Feminino , Hepatectomia , Humanos , Masculino , Estresse Oxidativo , Gravidez , Ratos Sprague-Dawley , Transdução de Sinais
8.
J Surg Res ; 219: 33-42, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-29078901

RESUMO

BACKGROUND: Hispanic ethnicity is associated with increased incidence of gallbladder disease. Additionally, ethnicity has been shown to be an outcome determinant in several conditions and procedures but has never been studied as a potential determinant of morbidity or mortality after laparoscopic or open cholecystectomy. METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program database, patients who underwent cholecystectomy and related procedures were studied in Hispanic and non-Hispanic cohorts. Mortality and postoperative complication rates were calculated and adjusted for patient demographics and comorbidities through multivariate analysis. RESULTS: Hispanics had decreased morbidity following cholecystectomy as compared to non-Hispanics on univariate analysis in combined, laparoscopic, and open cohorts (RR 0.64, P value < 0.001; 0.68, <0.001; 0.77, <0.001, respectively). The reduction was not found to be statistically significant in multivariate analysis. A similar reduction was seen for mortality (RR 0.30, <0.001; 0.39, <0.001; 0.28, <0.001, respectively) which remained on multivariate analysis in both combined and open cohorts (RR 0.63, 0.008 and 0.48, 0.021, respectively). Additionally, the rates of several postoperative complications were found to be reduced in Hispanic patients. Though our study demonstrates a lower rate of established comorbidities for poor outcomes in Hispanics, after adjustment in multivariate analysis, the entirety of the reduced risk could not be accounted for. CONCLUSIONS: While the Hispanic cohort has an increased incidence in gallbladder disease as compared to non-Hispanics, the complication, morbidity, and mortality rates are lower in unadjusted analysis. With adjustment, morbidity was not statistically significant and mortality was only significant in combined and open cohorts. This suggests that increased incidence rates do not equate with worse outcomes, but Hispanic ethnicity may be associated with better outcomes.


Assuntos
Colecistectomia , Disparidades nos Níveis de Saúde , Hispânico ou Latino , Complicações Pós-Operatórias/etnologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Colecistectomia/métodos , Colecistectomia/mortalidade , Colecistectomia Laparoscópica/mortalidade , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Avaliação de Resultados em Cuidados de Saúde , Complicações Pós-Operatórias/mortalidade , Estados Unidos , Adulto Jovem
9.
Macromol Rapid Commun ; 36(23): 2055-9, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26344702

RESUMO

This Communication describes a new light-controlled release system based on molecular recognition of cyclodextrins. Azobenzene (Azo) residue is employed as a photoresponsive guest residue because it can switch the partner from α-cyclodextrin (αCD) to ß-cyclodextrin (ßCD) by irradiation with UV light. Poly(sodium acrylate)s possessing αCD, ßCD, and Azo residues (pAαCD, pAßCD, and pAAzo, respectively) are mixed in aqueous solutions to form aggregates through the formation of inclusion complexes of Azo with αCD and/or ßCD. A chemical cargo, 1-pyrenemethylammonium chloride (PyMA), is contained in the aggregates, and its release behavior is investigated by dialysis experiments under UV irradiation. These data indicate that the amount of PyMA released for the pAαCD/pAßCD/pAAzo ternary mixture is approximately three times as high as those for the pAαCD/pAAzo and pAßCD/pAAzo binary mixtures because of the light-controlled rearrangement of inclusion complexes.


Assuntos
Resinas Acrílicas/química , Compostos Azo/química , Ciclodextrinas/química , Raios Ultravioleta , Preparações de Ação Retardada/química
10.
BMC Complement Altern Med ; 14: 404, 2014 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-25324121

RESUMO

BACKGROUND: Although studies have shown that a large proportion of cancer patients use CAM, no study on CAM use amongst orthopaedic oncology patients has been published. Therefore, this study aims to determine the prevalence, characteristics and factors associated with CAM use amongst orthopaedic oncology patients. METHODS: All consecutive consenting patients/parents who presented at the Orthopaedic Oncology Clinic, University Malaya Medical Centre (1st January to 31st December 2013) were interviewed using a structured questionnaire. RESULTS: Overall, one hundred sixty-eight of the 274 patients recruited (61.3%) had used CAM at some time during their current illness. The prevalence of CAM used was 68% (123/181) for patients with malignant tumours and 48.4% (45/93) for patients with benign tumours. The most popular CAMs were biological-based therapies (90.5%), followed by mind-body techniques (40.5%). The most frequently used biological therapies were mega/multivitamins (31%), snakehead (Chana striatus) (28%) and sea cucumber (Stichopus horrens) (18%); whereas prayers (31%) and holy water (13%) dominated the mind-body category. Common reasons for CAM use were to improve physical well-being (60.1%), try out everything that would help (59.5%) and to enhance wound-healing (39.3%). Independent predictors for CAM use in multivariate analysis were paediatric patients [OR 2.46; 95% CI 0.99-6.06; p = 0.05], malignant tumours [OR 1.90; 95% CI 1.12-3.25; p = 0.018] and patients who underwent surgery [OR 2.06; 95% CI 1.15-3.69; p = 0.015]. Majority patients started taking CAMs following suggestions from family members (53%) and friends (49%). Sixty-six percent of patients felt they actually benefitted from CAM and 83.3% were satisfied/very satisfied. Only 5 patients reported side-effects. Majority of CAM users planned to continue CAM use or recommend it to others. However, only 31.5% of patients disclosed their CAM usage to their doctors. CONCLUSIONS: This survey revealed a high prevalence of CAM usage amongst orthopaedic oncology patients, with majority patients expressing satisfaction towards CAM. Oncologists should proactively ask patients about CAM to prevent potential adverse effects, as most patients do not share this information with them.


Assuntos
Neoplasias Ósseas/terapia , Terapias Complementares , Neoplasias de Tecidos Moles/terapia , Adolescente , Adulto , Idoso , Neoplasias Ósseas/psicologia , Estudos Transversais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Malásia , Masculino , Pessoa de Meia-Idade , Ortopedia , Prevalência , Estudos Prospectivos , Neoplasias de Tecidos Moles/psicologia , Inquéritos e Questionários , Adulto Jovem
11.
Physiol Meas ; 45(7)2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-38986482

RESUMO

Objective.Cardiac Index (CI) is a key physiologic parameter to ensure end organ perfusion in the pediatric intensive care unit (PICU). Determination of CI requires invasive cardiac measurements and is not routinely done at the PICU bedside. To date, there is no gold standard non-invasive means to determine CI. This study aims to use a novel non-invasive methodology, based on routine continuous physiologic data, called Pulse Arrival Time (PAT) as a surrogate for CI in patients with normal Ejection Fraction (EF).Approach.Electrocardiogram (ECG) and photoplethysmogram (PPG) signals were collected from beside monitors at a sampling frequency of 250 samples per second. Continuous PAT, derived from the ECG and PPG waveforms was averaged per patient. Pearson's correlation coefficient was calculated between PAT and CI, PAT and heart rate (HR), and PAT and EF.Main Results.Twenty patients underwent right heart cardiac catheterization. The mean age of patients was 11.7 ± 5.4 years old, ranging from 11 months old to 19 years old, the median age was 13.4 years old. HR in this cohort was 93.8 ± 17.0 beats per minute. The average EF was 54.4 ± 9.6%. The average CI was 3.51 ± 0.72 l min-1m-2, with ranging from 2.6 to 4.77 l min-1m-2. The average PAT was 0.31 ± 0.12 s. Pearson correlation analysis showed a positive correlation between PAT and CI (0.57,p< 0.01). Pearson correlation between HR and CI, and correlation between EF and CI was 0.22 (p= 0.35) and 0.03 (p= 0.23) respectively. The correlation between PAT, when indexed by HR (i.e. PAT × HR), and CI minimally improved to 0.58 (p< 0.01).Significance.This pilot study demonstrates that PAT may serve as a valuable surrogate marker for CI at the bedside, as a non-invasive and continuous modality in the PICU. The use of PAT in clinical practice remains to be thoroughly investigated.


Assuntos
Transplante de Coração , Volume Sistólico , Humanos , Criança , Adolescente , Pré-Escolar , Masculino , Feminino , Lactente , Volume Sistólico/fisiologia , Adulto Jovem , Frequência Cardíaca/fisiologia , Eletrocardiografia , Pulso Arterial , Fotopletismografia , Fatores de Tempo
12.
bioRxiv ; 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39314429

RESUMO

Retrospective epidemiological studies suggest that the licensed serogroup B meningococcal vaccine 4CMenB (Bexsero) provides some protection against the closely related pathogen Neisseria gonorrhoeae in humans. This result has been replicated in murine models of gonococcal colonization, with a gonococci-reactive humoral response and more rapid clearance of vaginal infection. However, immunization with Bexsero consistently elicits a robust humoral response but does not protect all individuals, so the correlates of protection remain undefined. Herein, we exploit the fact that Bexsero promotes clearance in only a subset of immunized mice to perform a broad analysis of the adaptive response in animals that are or are not protected. We observe that Bexsero vaccination induces high levels of anti-neisserial antibodies in both serum and the vaginal lumen, and a robust cellular response highlighted by an increase in both conventional naive and memory populations as well as unconventional lymphocyte subsets. Multiplex and flow cytometry results show that Bexsero vaccination generates a robust, multi-faceted cytokine response that spans numerous T cell subsets (TH1, TH2, Treg and TH17 responses) and that non-T non-B lymphocytes play an important role in this response, as indicated by an unbiased principal component analysis. Together, this work provides the first comprehensive analysis of the robust humoral and complex cellular response to Bexsero so as to reveal the effector mechanisms that may contribute to immunity against vaginal gonococcal infection.

13.
bioRxiv ; 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39282262

RESUMO

Neisseria meningitidis is a human-restricted bacteria that is a normal nasopharyngeal resident, yet it can also disseminate, causing invasive meningococcal disease. Meningococci are highly adapted to life in humans, with human-specific virulence factors contributing to bacterial adhesion, nutrient acquisition and immune evasion. While these factors have been explored in isolation, their relative contribution during infection has not been considered due to their absence in small animal models and their expression by different human cell types not readily combined in either in vitro or ex vivo systems. Herein, we show that transgenic expression of the iron-binding glycoproteins human transferrin and lactoferrin can each facilitate N. meningitidis replication in mouse serum but that transferrin was required to support infection-induced sepsis. While these host proteins are insufficient to allow nasopharyngeal colonization alone, mice co-expressing these and human CEACAM1 support robust colonization. In this case, meningococcal colonization elicits an acute elevation in both transferrin and lactoferrin levels within the upper respiratory mucosa, with transferrin levels remaining elevated while lactoferrin returns to basal levels after establishment of infection. Competitive infection of triple transgenic animals with transferrin- and lactoferrin- binding protein mutants selects for bacteria expressing the transferrin receptor, implicating the critical contribution of transferrin-based iron acquisition to support colonization. These transgenic animals have thus allowed us to disentangle the relative contribution of three virulence factors during colonization and invasive disease, and provides a novel in vivo model that can support extended meningococcal colonization, opening a new avenue to explore the meningococcal lifestyle within its primary niche.

14.
J AOAC Int ; 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39255252

RESUMO

BACKGROUND: A multi-laboratory validation study was performed on AOAC Official Method of Analysis (OMA) 2016.09, for final action. Eight different laboratories throughout the world participated in the study tested the same set of 6 different laboratory samples of raw materials (commercial) and formulated products (commercial), and all the laboratories successfully generated results within the acceptance criteria. OBJECTIVE: The intention of the study was to evaluate specificity, precision (variation), linearity/range, system suitability, limit of detection (LOD), and limit of quantitation (LOQ) by multiple laboratories to satisfy the requirement of moving the OMA 2016.09 to the final action status. Accuracy and ruggedness were already validated in earlier work of single laboratory validation (1), and it was not necessary to include these validation parameters in the multi-laboratory validation study. METHOD: Laboratory samples containing Aloe were sent out to participating laboratories. Each lab followed AOAC 2016.09 (First Action status) to analyze contents of aloin A, aloin B, and aloe emodin using high performance liquid chromatography (HPLC) instrument. The results generated by each laboratory were collected and evaluated. RESULTS: The specificity results show that blank and matrix chromatograms do not contain major interfering peaks on the retention time of aloin A, aloin B, and aloe-emodin. The precision (variation) results of duplicated preparations are not more than 0.05 parts per million (ppm) different. The linearity/range results from six standards (10 parts per billion (ppb), 20 ppb, 40 ppb, 80 ppb, 160 ppb, and 500 ppb) have correlation coefficient (R) value of ≥ 0.999. The system suitability results meet the acceptance criteria to show the instrument validity. The limit of detection (LOD) results show that the signal-to-noise (S/N) ratio of 10 ppb standards for all three components are about 3. The limit of quantitation (LOQ) results show that the S/N ratio of 20 ppb standards for all three components are about 10. CONCLUSIONS: The validation parameters (specificity, precision (variation), linearity/range, system suitability, LOD, and LOQ) have been successfully analyzed, and it shows that the test method is suitable for its intended use. HIGHLIGHTS: The test method has been successfully validated by the eight different laboratories around the world (US, UK, Germany, and Canada). Each of the laboratory is managed independently by the site lab management team. This multi-lab study validated the method of Determination of Aloin A, Aloin B, and Aloe-Emodin in Raw Materials and Finished Products Using high performance liquid chromatography (HPLC), and the method fits for its intended purpose.

15.
Front Public Health ; 11: 1168551, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37727605

RESUMO

Standard multiplex RT-qPCR diagnostic tests use nasopharyngeal swabs to simultaneously detect a variety of infections, but commercially available kits can be expensive and have limited throughput. Previously, we clinically validated a saliva-based RT-qPCR diagnostic test for SARS-CoV-2 to provide low-cost testing with high throughput and low turnaround time on a university campus. Here, we developed a respiratory diagnostic panel to detect SARS-CoV-2, influenza A and B within a single saliva sample. When compared to clinical results, our assay demonstrated 93.5% accuracy for influenza A samples (43/46 concordant results) with no effect on SARS-CoV-2 accuracy or limit of detection. In addition, our assay can detect simulated coinfections at varying virus concentrations generated from synthetic RNA controls. We also confirmed the stability of influenza A in saliva at room temperature for up to 5 days. The cost of the assay is lower than standard nasopharyngeal swab respiratory panel tests as saliva collection does not require specialized swabs or trained clinical personnel. By repurposing the lab infrastructure developed for the COVID-19 pandemic, our multiplex assay can be used to provide expanded access to respiratory disease diagnostics, especially for community, school, or university testing applications where saliva testing was effectively utilized during the COVID-19 pandemic.


Assuntos
COVID-19 , Doenças Transmissíveis , Influenza Humana , Humanos , SARS-CoV-2 , Universidades , COVID-19/diagnóstico , COVID-19/epidemiologia , Pandemias
16.
Diagnostics (Basel) ; 14(1)2023 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-38201393

RESUMO

Copy number variation (CNV) is a primary source of structural variation in the human genome, leading to several disorders. Therefore, analyzing neonatal CNVs is crucial for managing CNV-related chromosomal disabilities. However, genomic waves can hinder accurate CNV analysis. To mitigate the influences of the waves, we adopted a machine learning approach and developed a new method that uses a modified log R ratio instead of the commonly used log R ratio. Validation results using samples with known CNVs demonstrated the superior performance of our method. We analyzed a total of 16,046 Korean newborn samples using the new method and identified CNVs related to 39 genetic disorders were identified in 342 cases. The most frequently detected CNV-related disorder was Joubert syndrome 4. The accuracy of our method was further confirmed by analyzing a subset of the detected results using NGS and comparing them with our results. The utilization of a genome-wide single nucleotide polymorphism array with wave offset was shown to be a powerful method for identifying CNVs in neonatal cases. The accurate screening and the ability to identify various disease susceptibilities offered by our new method could facilitate the identification of CNV-associated chromosomal disease etiologies.

17.
Cancers (Basel) ; 15(18)2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37760525

RESUMO

Early detection of lung cancer is crucial for patient survival and treatment. Recent advancements in next-generation sequencing (NGS) analysis enable cell-free DNA (cfDNA) liquid biopsy to detect changes, like chromosomal rearrangements, somatic mutations, and copy number variations (CNVs), in cancer. Machine learning (ML) analysis using cancer markers is a highly promising tool for identifying patterns and anomalies in cancers, making the development of ML-based analysis methods essential. We collected blood samples from 92 lung cancer patients and 80 healthy individuals to analyze the distinction between them. The detection of lung cancer markers Cyfra21 and carcinoembryonic antigen (CEA) in blood revealed significant differences between patients and controls. We performed machine learning analysis to obtain AUC values via Adaptive Boosting (AdaBoost), Multi-Layer Perceptron (MLP), and Logistic Regression (LR) using cancer markers, cfDNA concentrations, and CNV screening. Furthermore, combining the analysis of all multi-omics data for ML showed higher AUC values compared with analyzing each element separately, suggesting the potential for a highly accurate diagnosis of cancer. Overall, our results from ML analysis using multi-omics data obtained from blood demonstrate a remarkable ability of the model to distinguish between lung cancer and healthy individuals, highlighting the potential for a diagnostic model against lung cancer.

18.
Cureus ; 14(9): e29338, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36277538

RESUMO

Sigmoid volvulus and small bowel obstruction are typically thought to be separate clinical pathologies with distinct clinical features, diagnostic criteria, and treatment strategies. We present a rare case of simultaneous sigmoid volvulus and small bowel obstruction. To our knowledge, this is the first such case in literature and presented a unique set of challenges in regard to treatment and management. This case discusses a different approach to the surgical management of sigmoid volvulus and small bowel obstruction, which is markedly different from the expected and traditional surgical management of isolated sigmoid volvulus and small bowel obstruction.

19.
J Health Care Poor Underserved ; 33(2): 779-789, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35574876

RESUMO

OBJECTIVE: This study evaluated the impact of eConsults on access to specialty care for uninsured patients in Central Texas. METHODS: eConsults for four specialties, cardiology, gastroenterology, rheumatology, and endocrinology, were implemented in a large, multi-site federally qualified health center. Data were collected on specialty care access and utilization for a one-year period before and after implementation of the new process. RESULTS: Prior to implementation, 23% of uninsured patients referred to the included specialties completed a visit with a specialist. After implementation, 62% received a specialty consultation either through an eConsult or with a face-to-face visit. Wait times for referrals improved from a median of 54 days to seven days. CONCLUSION: This project demonstrated that eConsults improve access and reduce wait times for specialty care for uninsured patients. Interventions such as this have the potential to reduce health inequalities by providing timely access to care for common specialty concerns.


Assuntos
Medicina , Consulta Remota , Acessibilidade aos Serviços de Saúde , Humanos , Pessoas sem Cobertura de Seguro de Saúde , Atenção Primária à Saúde , Encaminhamento e Consulta , Texas
20.
Cureus ; 14(1): e20936, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35154921

RESUMO

Background The advent of the coronavirus disease 2019 (COVID-19) has generated varying opinions toward adhering to safety protocols among public health experts. With decreasing restrictions on public gatherings, lax protective behaviors, distortion of facts, and increasing availability of COVID-19 vaccines, response to public health guidelines vary greatly. Personal experiences with COVID-19, education, and work environment may influence decisions on safety recommendations and vaccination protocols among the public and healthcare professionals alike. To better understand how individuals process and make decisions regarding COVID-19 safety measures, this study investigated the attitudes among clinical and non-clinical healthcare workers and non-healthcare workers toward COVID-19 safety protocols. Methodology Cross-sectional data were collected from Florida residents using an online, 20-item anonymous questionnaire. Participants were recruited using the Florida Department of Health database for physician emails, social media, and snowball sampling strategies. The survey consisted of demographic items and questions regarding patient attitudes toward safety protocols for COVID-19 (e.g., likeliness to wear a mask in public despite state regulations being lifted, maintaining a distance of at least 6 feet between close friends and family, dining at restaurants/bars, gathering in groups larger than 10 people, getting a COVID-19 vaccine if one becomes available). Data were analyzed using one-way analysis of variance and chi-square test using SPSS version 27 (IBM Corp., Armonk, NY, USA). Results Of the 373 participants who completed the survey, 183 (49.1%) worked in the healthcare field, with 100 (28.6%) providing direct patient care. The rest (n = 190; 50.9%) reported that they do not work in the healthcare industry. Findings suggest that those working in healthcare with direct involvement in patient care were more likely to get the COVID-19 vaccine than those not working in healthcare. Additionally, those working in healthcare and providing direct patient care were more likely to think that masks were effective in reducing the spread of COVID-19 compared to those who worked in healthcare but did not provide direct patient care. Conclusions This study provides new insights into the attitudes of front-line clinicians, non-clinical healthcare workers, and the general population. Increasing health promotion efforts and debunking myths about COVID-19 may prove useful in mitigating the spread of the disease.

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