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Impaired cholesterol efflux and/or uptake can influence arterial lipid accumulation leading to atherosclerosis. Here, we report that tripartite motif-containing protein 13 (TRIM13), a RING-type E3 ubiquitin ligase, plays a role in arterial lipid accumulation leading to atherosclerosis. Using molecular approaches and KO mouse model, we found that TRIM13 expression was induced both in the aorta and peritoneal macrophages (pMφ) of ApoE-/- mice in response to Western diet (WD) in vivo. Furthermore, proatherogenic cytokine interleukin-1ß also induced TRIM13 expression both in pMφ and vascular smooth muscle cells. Furthermore, we found that TRIM13 via ubiquitination and degradation of liver X receptor (LXR)α/ß downregulates the expression of their target genes ABCA1/G1 and thereby inhibits cholesterol efflux. In addition, TRIM13 by ubiquitinating and degrading suppressor of cytokine signaling 1/3 (SOCS1/3) mediates signal transducer and activator of transcription 1 (STAT1) activation, CD36 expression, and foam cell formation. In line with these observations, genetic deletion of TRIM13 by rescuing cholesterol efflux and inhibiting foam cell formation protects against diet-induced atherosclerosis. We also found that while TRIM13 and CD36 levels were increased, LXRα/ß, ABCA1/G1, and SOCS3 levels were decreased both in Mφ and smooth muscle cells of stenotic human coronary arteries as compared to nonstenotic arteries. More intriguingly, the expression levels of TRIM13 and its downstream signaling molecules were correlated with the severity of stenotic lesions. Together, these observations reveal for the first time that TRIM13 plays a crucial role in diet-induced atherosclerosis, and that it could be a potential drug target against this vascular lesion.
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Aterosclerosis , Colesterol , Células Espumosas , Lipoproteínas LDL , Proteínas de Motivos Tripartitos , Ubiquitina-Proteína Ligasas , Animales , Humanos , Masculino , Ratones , Aterosclerosis/metabolismo , Aterosclerosis/patología , Aterosclerosis/genética , Transportador 1 de Casete de Unión a ATP/metabolismo , Transportador 1 de Casete de Unión a ATP/genética , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 1/metabolismo , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 1/genética , Colesterol/metabolismo , Dieta Occidental/efectos adversos , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Células Espumosas/metabolismo , Células Espumosas/patología , Lipoproteínas LDL/metabolismo , Receptores X del Hígado/metabolismo , Receptores X del Hígado/genética , Ratones Noqueados para ApoE , Células RAW 264.7 , Factor de Transcripción STAT1/metabolismo , Factor de Transcripción STAT1/genética , Proteínas de Motivos Tripartitos/genética , Proteínas de Motivos Tripartitos/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , UbiquitinaciónRESUMEN
BACKGROUND: Retinal neovascularization is a major cause of vision impairment. Therefore, the purpose of this study is to investigate the mechanisms by which hypoxia triggers the development of abnormal and leaky blood vessels. METHODS: A variety of cellular and molecular approaches as well as tissue-specific knockout mice were used to investigate the role of Cttn (cortactin) in retinal neovascularization and vascular leakage. RESULTS: We found that VEGFA (vascular endothelial growth factor A) stimulates Cttn phosphorylation at Y421, Y453, and Y470 residues in human retinal microvascular endothelial cells. In addition, we observed that while blockade of Cttn phosphorylation at Y470 inhibited VEGFA-induced human retinal microvascular endothelial cell angiogenic events, suppression of Y421 phosphorylation protected endothelial barrier integrity from disruption by VEGFA. In line with these observations, while blockade of Cttn phosphorylation at Y470 negated oxygen-induced retinopathy-induced retinal neovascularization, interference with Y421 phosphorylation prevented VEGFA/oxygen-induced retinopathy-induced vascular leakage. Mechanistically, while phosphorylation at Y470 was required for its interaction with Arp2/3 and CDC6 facilitating actin polymerization and DNA synthesis, respectively, Cttn phosphorylation at Y421 leads to its dissociation from VE-cadherin, resulting in adherens junction disruption. Furthermore, whereas Cttn phosphorylation at Y470 residue was dependent on Lyn, its phosphorylation at Y421 residue required Syk activation. Accordingly, lentivirus-mediated expression of shRNA targeting Lyn or Syk levels inhibited oxygen-induced retinopathy-induced retinal neovascularization and vascular leakage, respectively. CONCLUSIONS: The above observations show for the first time that phosphorylation of Cttn is involved in a site-specific manner in the regulation of retinal neovascularization and vascular leakage. In view of these findings, Cttn could be a novel target for the development of therapeutics against vascular diseases such as retinal neovascularization and vascular leakage.
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Neovascularización Retiniana , Animales , Humanos , Ratones , Cortactina/genética , Cortactina/metabolismo , Células Endoteliales/metabolismo , Ratones Noqueados , Oxígeno/metabolismo , Fosforilación , Neovascularización Retiniana/genética , Neovascularización Retiniana/metabolismo , Tirosina/efectos adversos , Tirosina/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
BACKGROUND: Uterine serous cancer (USC) comprises around 10% of all uterine cancers. However, USC accounts for approximately 40% of uterine cancer deaths, which is attributed to tumor aggressiveness and limited effective treatment. Galectin 3 (Gal3) has been implicated in promoting aggressive features in some malignancies. However, Gal3's role in promoting USC pathology is lacking. METHODS: We explored the relationship between LGALS3 levels and prognosis in USC patients using TCGA database, and examined the association between Gal3 levels in primary USC tumors and clinical-pathological features. CRISPR/Cas9-mediated Gal3-knockout (KO) and GB1107, inhibitor of Gal3, were employed to evaluate Gal3's impact on cell function. RESULTS: TCGA analysis revealed a worse prognosis for USC patients with high LGALS3. Patients with no-to-low Gal3 expression in primary tumors exhibited reduced clinical-pathological tumor progression. Gal3-KO and GB1107 reduced cell proliferation, stemness, adhesion, migration, and or invasion properties of USC lines. Furthermore, Gal3-positive conditioned media (CM) stimulated vascular tubal formation and branching and transition of fibroblast to cancer-associated fibroblast compared to Gal3-negative CM. Xenograft models emphasized the significance of Gal3 loss with fewer and smaller tumors compared to controls. Moreover, GB1107 impeded the growth of USC patient-derived organoids. CONCLUSION: These findings suggest inhibiting Gal3 may benefit USC patients.
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Proteínas Sanguíneas , Cistadenocarcinoma Seroso , Galectina 3 , Neoplasias Uterinas , Humanos , Femenino , Neoplasias Uterinas/patología , Neoplasias Uterinas/genética , Neoplasias Uterinas/metabolismo , Galectina 3/genética , Galectina 3/metabolismo , Cistadenocarcinoma Seroso/patología , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/metabolismo , Proliferación Celular , Línea Celular Tumoral , Pronóstico , Animales , Ratones , Galectinas/genética , Galectinas/metabolismo , Movimiento CelularRESUMEN
Bacterial infections present a major global health threat, often displaying resistance to various antibiotics. Lipoteichoic acid (LTA) is a vital component of bacterial cell envelopes of Gram-positive bacteria, crucial for cell integrity, cell division, and host inflammation. Due to its essential role for bacteria, LTA and its biosynthesis are also attractive drug targets, however, there is only scant molecular knowledge on LTA and its precursor molecules in membranes. Here, we report the isolation and molecular characterization of diglucosyldiacylglycerol (Glc2-DAG), the glycolipid precursor molecule that anchors LTA in the bacterial plasma-membrane. Using a tailored growth medium and purification protocols, we isolated 13C-isotope labelled Glc2-DAG from bacteria, which can then be used for high-resolution NMR studies. Using solution-state and solid-state NMR, we show an in-depth molecular characterization of Glc2-DAG, including in native-like membranes. Our approach may help to identify antibiotics that directly target LTA precursor molecules, and it offers a tool for future investigations into the role of Glc2-DAG in bacterial physiology.
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Due to shrinkage in photopolymer materials, the angle of the reconstruction beam in holographic optical elements (HOEs) does not match with the Bragg condition, resulting in a decreased amount of light in the desired direction or loss of transmitted information to rematch the Bragg condition. Thus, to ensure final display features it is imperative to precompensate the shrinkage effect. We derived simplified expressions for precompensation in recording geometries of required HOEs in holographic waveguide-based Maxwellian near eye displays. An acceptable range of detuning from the Bragg angle is also analyzed. The experimentally measured 4.95% shrinkage in photopolymer film for 0° and 45° recording angles of beams was precompensated using -0.86∘ and 43.7° recording angles. Theoretical results are validated through simulation and experiments.
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OBJECTIVE: To describe the characteristics and outcomes of older (65+) Medicare beneficiaries with traumatic brain injury (TBI) treated in inpatient rehabilitation facilities between 2013 and 2018. DESIGN: Descriptive study using IRF Patient Assessment Instrument (IRF-PAI) data reporting trends of the sociodemographic and clinical characteristics and outcomes of inpatient rehabilitation facilities Medicare patients with TBI. SETTING: Inpatient rehabilitation facilities in the United States. PARTICIPANTS: 99,804 older Medicare fee-for-service and Medicare Advantage patients with TBI (N=99,804). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Length of stay, self-care, and mobility functional outcomes, discharge destination. RESULTS: The number of older Medicare beneficiaries with TBI treated in inpatient rehabilitation facilities increased from 14,657 in 2013 to 18,791 in 2018, an increase of 28.2%. In addition to this overall increase in patients, we also found the percentage of men increased slightly (52.9% to 54.8%), there was a higher percentage of patients with tier 3 comorbidities, there was a decrease in the variability of length of stay, there was slightly more self-care and mobility improvement and a slightly higher percentage of patients discharged to the community (67.8% in 2013 and 71.6% in 2018). Newer standardized data showed that prior to the injury, more than one-third used a walker and more than three-quarters had a history of recent falls. CONCLUSIONS: Between 2013 and 2018, the number of Medicare beneficiaries with TBI treated in IRFs increased by approximately 28%. The characteristics of IRF older patients with TBI changed between 2013 and 2018 toward a slightly higher proportion of men, more comorbidities, and a higher percentage being discharged home after inpatient rehabilitation.
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Lesiones Traumáticas del Encéfalo , Tiempo de Internación , Medicare , Centros de Rehabilitación , Humanos , Masculino , Femenino , Estados Unidos , Anciano , Lesiones Traumáticas del Encéfalo/rehabilitación , Centros de Rehabilitación/estadística & datos numéricos , Medicare/estadística & datos numéricos , Anciano de 80 o más Años , Tiempo de Internación/estadística & datos numéricos , Autocuidado , Pacientes Internos/estadística & datos numéricos , Alta del Paciente/estadística & datos numéricos , Planes de Aranceles por Servicios/estadística & datos numéricos , ComorbilidadRESUMEN
OBJECTIVE: The objectives of this study were to characterize and identify correlates of healthy days at home (HDaH) before and after TBI requiring inpatient rehabilitation. Setting: Inpatient hospital, nursing home, and home health services. PARTICIPANTS: Average of n= 631 community-dwelling fee-for-service age 66+ Medicare beneficiaries across 30 replicate samples who were hospitalized for traumatic brain injury (TBI) between 2012 and 2014 and admitted to an inpatient rehabilitation facility (IRF) within 72 hours of hospital discharge. DESIGN: Retrospective study using data from Medicare claims supplemented with data from the National Trauma Databank. MAIN MEASURES: The primary outcome, HDaH, was calculated as time alive not using inpatient hospital, nursing home, and home health services in the year before TBI hospitalization and after IRF discharge. RESULTS: We found HDaH declined from 93.2% in the year before TBI hospitalization to 65.3% in the year after IRF discharge (73.6% among survivors only). Most variability in HDaH was: (1) in the first 3 months after discharge and (2) by discharge disposition, with persons discharged from IRF to another acute hospital having the worst prognosis for utilization and death. In negative binomial regression models, the strongest predictors of HDaH in the year after discharge were rehabilitation Functional Independence Measure mobility score (ß = 0.03; 95% CI, 0.002-0.06) and inpatient Charlson Comorbidity Index score (ß = - 0.06; 95% CI, -0.13 to 0.001). Dual Medicaid eligible was associated with less HDaH among survivors (ß = - 0.37; 95% CI, -0.66 to -0.07). CONCLUSION: In this study, among community-dwelling older adults with TBI, we found a notable decrease in the proportion of time spent alive at home without higher-level care after IRF discharge compared to before TBI. The finding that physical disability and comorbidities were the biggest drivers of healthy days alive in this population suggests that a chronic disease management model is required for older adults with TBI to manage their complex health care needs.
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OBJECTIVE: This study aimed to characterize the types and timing of repetitive head impact (RHI) exposures in individuals with moderate to severe traumatic brain injury (TBI) and to examine the effects of RHI exposures on mental health outcomes. SETTING: TBI Model Systems National Database. PARTICIPANTS: 447 patients with moderate to severe TBI who reported RHI exposure between 2015 and 2022. DESIGN: Secondary data analysis. MAIN MEASURES: RHI exposures reported on the Ohio State University TBI Identification Method (OSU TBI-ID) were characterized by exposure category, duration, and timing relative to the index TBI. Mental health outcomes were evaluated at the 5-year follow-up assessment using the Patient Health Questionnaire-9 (PHQ-9) for depression symptoms and the Generalized Anxiety Disorder-7 (GAD-7) for anxiety symptoms. RESULTS: The majority of RHI exposures were sports-related (61.1%), followed by other causes (20.8%; including falls), repetitive violence/assault (18.8%), and military exposures (6.7%). Males predominantly reported sports and military exposures, while a larger proportion of females reported violence and falls. Sports exposures were most common before the index TBI, while exposures from falls and violence/abuse were most common after TBI. RHI exposures occurring after the index TBI were associated with higher levels of depression (ß = 5.05; 95% CI, 1.59-8.50) and anxiety (ß = 4.53; 95% CI, 1.02-8.05) symptoms than exposures before the index TBI. CONCLUSION: The findings emphasize the need to consider RHI exposures and their interaction with TBI when assessing mental health outcomes. Understanding the prevalence and challenges associated with RHI post-TBI can inform targeted interventions and improve the well-being of individuals with TBI. Preventive measures and ongoing care should be implemented to address the risks posed by RHI, particularly in individuals with prior TBI, especially surrounding fall and violence/abuse prevention.
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OBJECTIVES: To identify personal, clinical, and environmental factors associated with 4 previously identified distinct multidimensional participation profiles of individuals following traumatic brain injury (TBI). SETTING: Community. PARTICIPANTS: Participants (n = 408) enrolled in the TBI Model Systems (TBIMS) Participation Module, all 1 year or more postinjury. DESIGN: Secondary data analysis of cross-sectional data from participants in a multicenter TBIMS module study on participation conducted between May 2006 and September 2007. Participants provided responses to questionnaires via a telephone interview at their study follow-up (1, 2, 5, 10, or 15 years postinjury). MAIN MEASURES: Participants provided responses to personal (eg, demographic), clinical (eg, function), environmental (eg, neighborhood type), and participation measures to create multidimensional participation profiles. Data from measures collected at the time of injury (preinjury questionnaire, injury characteristics) were also included. The primary outcome was assignment to one of 4 multidimensional participation profile groups based on participation frequency, importance, satisfaction, and enfranchisement. The measures used to develop the profiles were: Participation Assessment with Recombined Tools-Objective, Importance, and Satisfaction scores, each across 3 domains (Productivity, Social Relationships, Out and About in the Community) and the Enfranchisement Scale (contributing to one's community, feeling valued by the community, choice and control). RESULTS: Results of the multinomial regression analysis, with 4 distinct participation profile groups as the outcome, indicated that education, current employment, current illicit drug use, current driving status, community type, and Functional Independence Measure Cognitive at follow-up significantly distinguished participation profile groups. Findings suggest a trend toward differences in participation profile groups by race/Hispanic ethnicity. CONCLUSIONS: Understanding personal, clinical, and environmental factors associated with distinct participation outcome profiles following TBI may provide more personalized and nuanced guidance to inform rehabilitation intervention planning and/or ongoing clinical monitoring.
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OBJECTIVE: To create a census-based composite neighborhood socioeconomic deprivation index (NSDI) from geocoded residential addresses and to quantify how NSDI aligns with individual-level socioeconomic factors among people with traumatic brain injury (TBI). SETTING: Community. PARTICIPANTS: People enrolled in the TBI Model Systems National Database (TBIMS NDB). DESIGN: Secondary analysis of a longitudinal cohort study. MAIN MEASURES: The TBIMS-NSDI was calculated at the census tract level for the United States population based on a principal components analysis of eight census tract-level variables from the American Community Survey. Individual socioeconomic characteristics from the TBIMS NDB were personal household income, education (years), and unemployment status. Neighborhood:Individual NSDI residuals represent the difference between predicted neighborhood disadvantage based on individual socioeconomic characteristics versus observed neighborhood disadvantage based on the TBIMS-NSDI. RESULTS: A single principal component was found to encompass the eight socioeconomic neighborhood-level variables. It was normally distributed across follow-up years 2, 5, and 10 post-injury in the TBIMS NDB. In all years, the TBIMS-NDSI was significantly associated with individual-level measures of household income and education but not unemployment status. Males, persons of Black and Hispanic background, Medicaid recipients, persons with TBI caused by violence, and those living in urban areas, as well as in the Northeast or Southern regions of the United States, were more likely to have greater neighborhood disadvantage than predicted based on their individual socioeconomic characteristics. CONCLUSIONS: The TBIMS-NSDI provides a neighborhood-level indicator of socioeconomic disadvantage, an important social determinant of outcomes from TBI. The Neighborhood:Individual NSDI residual adds another dimension to the TBIMS-NSDI by summarizing how a person's socioeconomic status aligns with their neighborhood socioeconomics. Future studies should evaluate how both measures affect TBI recovery and life quality. Research studying neighborhood socioeconomic disadvantage may improve our understanding of how systemic adversity influences outcomes after TBI.
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Carbon nanotube-FETs (CNTFETs) have become a potential challenger because of their exceptional electrical properties and compatibility with conventional CMOS technology. The design and study of digitally tunable transconductance amplifiers (DTTAs) using CNTFETs are the main topics of this work. By utilizing the special characteristics of CNTFETs, the suggested DTTA design makes transconductance tunable, providing a versatile method of adjusting amplifier settings without requiring modifications to the hardware architecture. This study provides a complete description of the CNTFET modeling techniques utilized for realistic circuit simulations, along with a detailed analysis of the DTTA based on CNTFETs. The circuit is implemented using a 32 nm CNTFET model and verified results with HSPICE.
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Digital holography (DH) is an important method for three-dimensional (3D) imaging since it allows for the recording and reconstruction of an object's amplitude and phase information. However, the field of view (FOV) of a DH system is typically restricted by the finite size of the pixel pitch of the digital image sensor. We proposed a new configuration of the DH system based on Fresnel's bi-mirror to achieve doubling the camera FOV of the existing off-axis DH system which leveraged single-shot acquisition and a common-path optical framework. The dual FOV was obtained by spatial frequency multiplexing corresponding to two different information-carrying beams from an object. Experimental evidence of the proposed dual FOV-DH system's viability was provided by imaging two different areas of the test object and an application to surface profilometry by measuring the step height of the resolution chart which showed excellent agreement with an optical profiler. Due to the simple configuration, the proposed system could find a wide range of applications, including in microscopy and optical metrology.
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Epigenetic modifications influence gene expression and effects cancer initiation and progression. Therefore, they serve as diagnostic and prognostic biomarkers and potential therapeutic targets. Natural Killer (NK) cells, integral to the innate immune system, exhibit anti-tumor effect by recognizing and eliminating cancerous cells through the balance of activating and inhibitory ligands. Understanding the epigenetic regulation of NK cell ligands offers insights into enhancing NK cell-mediated tumor eradication. This review explores the epigenetic modifications governing the expression of activating NKG2D ligands and discusses clinical trials investigating NK cell-based immunotherapies, highlighting their potential as effective cancer treatment strategies. Case studies examining the safety and effectiveness of NK cell therapies in different cancer types, such as acute myeloid leukemia (AML) and non-small cell lung cancer (NSCLC), demonstrate promising outcomes with minimal toxicity. These findings underscore the therapeutic prospects of epigenetic modulation of NKG2D ligands and NK cell-based immunotherapies as effective cancer treatment strategies. Future research in the advancement of personalized medicine approaches and novel combination therapies with NK cell will further improve treatment outcomes and provide new therapeutic options for treating patients with various types of cancer.
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Measurement of anisotropy factor (g) in the presence of nanoparticles (NPs) is important for understanding light distribution for plasmonic photothermal cancer therapeutics. Here, anisotropy factor is investigated through bilayer phantoms (epidermal and dermal) of various thicknesses incorporated with gold nanorods (GNRs) concentrations of 10-40 µg/mL by using in-house developed goniometric setup. Results show that 10 µg/mL GNRs in the phantom increase g by ~50% (g = 0.9471) w.r.t. phantom without NPs. Higher concentrations (40 µg/mL) of GNRs decrease g by ~43% (g = 0.5341) w.r.t. phantom with 10 µg/mL GNRs. For 40 µg/mL GNRs phantom, the anisotropy factor reduces by 47% for phantom thickness from 600 to 1800 µm. Anisotropy factor of GNR embedded phantom increased by 44% by using glycerol (10%-40%). Incorporation of NPs in a tumor significantly affects g, a major parameter for light distribution. These measurements provide insights for light scattering based on nanoparticle doses for plasmonic photothermal therapeutics.
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Oro , Neoplasias , Fantasmas de Imagen , Anisotropía , Oro/química , Neoplasias/terapia , Neoplasias/diagnóstico por imagen , Terapia Fototérmica , Nanotubos/química , Nanopartículas del Metal/química , HumanosRESUMEN
Introduction: The study discussed three patients who experienced both anterior cruciate ligament (ACL) injury and patellofemoral instability. This combination of injuries is rare and has a scarcity of published /literature. The study described the mechanism of injury, diagnostic modalities, and the decision-making process for surgical intervention. It emphasizes the importance of a comprehensive clinical evaluation and discusses surgical techniques for combined ACL and medial patellofemoral ligament (MPFL) reconstruction. The study suggests that with careful evaluation and meticulous surgical techniques, patients with concurrent ACL and MPFL injuries can achieve successful outcomes and return to normal activities. Case Report: The cases presented involve young patients who suffered twisting knee injuries, often resulting from accidents or sporting activities. The surgical technique involved the use of grafts for ACL and MPFL reconstruction. MPFL reconstruction was performed followed by ACL reconstruction. Post-operative rehabilitation included the use of a patellar stabilizing knee brace and gradual mobilization. Results: The patients experienced moderate pain initially but achieved a full range of motion and stability in the knee after several weeks. At the 1-year follow-up, both patients reported no symptoms of instability or pain. Conclusion: The article highlights the importance of MPFL reconstruction in preventing ACL reconstruction failures and emphasizes the need for aggressive rehabilitation to prevent knee stiffness. Overall, this study presented important information and added knowledge regarding the diagnosis, surgical management, and post-operative care of patients with concurrent ACL and patellofemoral instability.
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BACKGROUND: Frailty represents a state of risk in which a relatively small stressor results in a disproportionate decline in health status. This study aims to determine the prevalence of frailty among patients with COPD in the Indian population and its associated risk factors. METHODS: A descriptive cross-sectional study was conducted in 150 COPD patients. Frailty was assessed using the frailty phenotype method. RESULTS: The mean age (SD) of the study population was 60.59 (5.9) years with 88.67% males and 53.33% ex-smokers. The prevalence of frailty was 51.33% (n = 77). Most of the frail patients belonged to GOLD group D (66.23%) (P < 0.0001). Post-bronchodilator FEV1(%) was lowest in the frail group (40 [36-47]%) (P < 0.0001). Risk of frailty significantly correlated with smoking pack years (1.036; 1.001-1.074), history of 1 exacerbation in last year (6.810; 2.036-22.779), post-bronchodilator FVC(%) (0.955; 0.926-0.985), post-bronchodilator FEV1(%) (0.940; 0.913-0.968), distance covered in 6-minute walk test [0.975; 0.965-0.986] and dyspnoea severity [1.044; 1.024-1.063]. In multivariate regression, 6-minute walk distance and GOLD group B were the independent predictors of frailty in COPD. CONCLUSION: The prevalence of frailty in Indian patients with COPD was 51.33%. Six-minute walk distance is an important predictor of frailty. Early identification of frailty will lead to prompt intervention and rehabilitation.
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OBJECTIVE: Hypersensitivity pneumonitis (HP) is an inflammatory and/or fibrotic lung disease. The restrictive lung function with low diffusing capacity of carbon monoxide (DLCO) is common in interstitial lung diseases (ILD). There are limited data on pulmonary function test (PFT) in HP and its role for diagnosis is questionable. We analyzed the data of 152 HP patients for type of defect, lung volume, and DLCO. MATERIAL AND METHODS: The present study is a retrospective analysis of 152 patients at one of the tertiary chest institutes in India. All diagnosed cases with at least spirometry were included. PFT findings were classified and graded as obstructive, restrictive, and mixed patterns. The correlation of PFT was calculated with disease duration and 6MWT distance. RESULTS: The majority were female [106 (70%)], with a mean age of 47.8 ± 12.3 years. Spirometry with lung volume data were available for 97% patients. PFT was abnormal in 118 (80%) cases. Among the patterns of abnormality, the most common type was restrictive (74%) followed by mixed (15%) and obstructive (11%) with the majority in the severe to very severe grade. The mean total lung capacity (TLC) and residual volume (RV) were reduced, with the grade more severe when the pattern of abnormality was restrictive while the RV/ TLC was higher suggestive of air tapping. DLCO data were available for 132 (87%) cases, with levels decreased in 67%. The severity of DLCO was highest when the pattern of abnormality was restrictive. One of the PFT parameters was abnormal in 137 (90%) cases, with isolated decreased DLCO levels seen in 16 (10%) cases. Forced vital capacity (FVC), TLC, and DLCO showed positive correlation with 6MWT distance (FVC r = .22, P = .02; TLC r = .28, P = .003; DLCO r = .30, P = .002). CONCLUSION: The PFT abnormality is seen in >80% of HP patients. All types of abnormality were seen, with the restrictive pattern being the most common. Isolated decreased DLCO levels were seen in 10% of cases. We advised to do full PFT for diagnosis and followup of HP.
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Malignant phyllodes, along with ductal carcinoma, is known as metaplastic cancer of the breast. This tumor is additionally known as breast carcinosarcoma. Malignant phyllodes in conjunction with ductal carcinoma is a rare finding in routine clinical practice. We describe the case report of a 47-year-old female patient who arrived with a large right breast mass. A core biopsy was performed, and histopathological examination indicated that the tumor was a malignant phyllodes tumor. A positron emission tomography (PET) scan revealed hyper-metabolic and hypo-metabolic tumors with perilesional stranding and satellite nodularity. There were a few metastatic right axillary nodes visible. There was no indication of distant metastases. Due to the presence of both components, a modified radical mastectomy surgery with axillary dissection was undertaken for this patient. Histopathological analysis of paraffin sections revealed ductal carcinoma in situ (DCIS) comedo-epithelial component and spindle-shaped cells with hyper-chromatic oval nuclei and scanty cytoplasm.
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Foodborne infections pose a substantial global threat, causing an estimated 600 million illnesses and resulting in approximately 420,000 deaths annually. Among the diverse array of pathogens implicated in these infections, Escherichia coli (E. coli), specifically the O157 strain (E. coli O157), emerges as a prominent pathogen associated with severe outbreaks. This study employs a comprehensive bibliometric analysis and scholarly review focused on E. coli O157 research. The bibliometric analysis highlights the significant role played by the United States in the E. coli O157 research domain. Further exploration underscores the noteworthy contributions of the researcher Doyle MP, whose body of work, consisting of 84 documents and an impressive H-Index of 49, reflects their substantial impact in the field. Recent research trends indicate a discernible shift towards innovative detection methods, exemplified by the adoption of CRISPR-CAS and Loop-Mediated Isothermal Amplification. Moreover, high-throughput whole-genome sequencing techniques are gaining prominence for the expeditious analysis of pathogenic E. coli strains. Scientists are increasingly exploring antimicrobial agents, including phage therapy, to address the challenges posed by antibiotic-resistant E. coli strains, thereby addressing critical concerns related to multi-drug resistance. This comprehensive analysis provides vital insights into the dynamic landscape of E. coli O157 research. It serves as a valuable resource for researchers, policymakers, and healthcare professionals dedicated to mitigating E. coli O157 outbreaks and advancing global public health strategies.
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Micro-electrical discharge machining (µEDM) is severely affected by tool wear and its process variants, which can lead to compromised precision and dimensional disruptions in micro-part production. Several attempts have been made to address this problem by suggesting offline and online (real-time) tool wear compensation strategies. Research efforts in this area have intensified over the last 20 years. However, most methods proposed were applicable only for a few work-tool combinations and in limited input process parametric settings. Instead of tool wear compensation, several research articles have focused on strategies to reduce the negative impact of tool wear on the quality of fabricated parts. The present study systematically reviews various investigations conducted in this area and aims to add cutting-edge compensation for tool wear to future inquiries. The articles reviewed here are explored in detail. Critical findings/innovations are classified into four categories: tool wear in µEDM, tool wear compensation techniques, and offline and online compensation methods.