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INTRODUCTION: When irradiating thoracic tumors, dose to the heart or lung has been associated with survival. We previously showed in a rat model that in addition to known side-effects such as pericarditis, pneumonitis and fibrosis, heart and/or lung irradiation also impaired diastolic function and increased pulmonary artery pressure. Simultaneous irradiation of both organs strongly intensified these effects. However, the long-term consequences of this interactions are not yet known. Therefore, here we investigate the long-term effects of combined heart and lung irradiation. MATERIAL AND METHODS: Different regions of the rat thorax containing the heart and/or 50% of the lungs were irradiated with protons. Respiratory rate (RR) was measured bi-weekly as an overall parameter for cardiopulmonary function. Echocardiography of the heart was performed at 8, 26 and 42 weeks after irradiation. Tissue remodeling and vascular changes were assessed using Masson Trichrome and Verhoeff-stained lung and LV tissue collected at 8 and 42 weeks after irradiation. RESULTS: During the entire experimental period RR was consistently increased after combined heart/lung irradiation. This coincided with persistent effects on lung vasculature and reduced right ventricle contraction. In contrast, recovery of RR, pulmonary remodeling and right ventricle contraction was observed after sparing of the heart. These corresponding temporal patterns suggest that the reduction of right ventricle (RV) function is related to vascular remodeling in the lung. CONCLUSION: Combined irradiation of lung and heart leads to an intensified, persistent reduction of cardiopulmonary function. Recovery of the pulmonary vasculature and right ventricle function requires heart-sparing.
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INTRODUCTION: The aim of this study was to examine the association between the injury mechanism and repair type with outcomes in patients with traumatic inferior vena cava injuries. METHODS: This is a retrospective analysis of the ACS-TQIP database (2017-2020), including patients with traumatic IVC injuries. Patients were stratified by injury mechanism and type of repair and compared. RESULTS: Out of 1334 patients, 5 â% underwent endovascular repair while 95 â% had an open procedure. Overall, 74.7 â% sustained a penetrating injury. On multivariable regression analysis, the type of repair was not associated with mortality and morbidity for patients with penetrating injuries. However, among patients with blunt injuries, endovascular repair was associated with lower odds of in-hospital mortality (aOR:0.35, p â= â0.020) and non-venous thromboembolism (VTE) morbidity (aOR:0.41, p â= â0.015), and higher odds of VTE complications (aOR:6.74, p â< â0.001). CONCLUSIONS: Although the type of repair did not impact morbidity and mortality in patients with penetrating injuries, endovascular repair was identified as the only modifiable predictor of reduced non-VTE morbidity and mortality in patients with blunt injuries.
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INTRODUCTION: Distal femur fractures are complex injuries that often present with multiple fragments, posing notable challenges to fixation. This study aimed to (1) use preoperative CT scans to graphically display fracture lines in intra-articular distal femur fractures and (2) identify common fracture patterns in these injuries. METHODS: All skeletally mature patients that underwent surgical fixation of Orthopaedic Trauma Association type 33C distal femur fractures between 2012 and 2022 were identified across two level 1 trauma centers (n = 63). Preoperative axial, sagittal, and coronal computed tomography scans were obtained. Fracture lines in each plane were traced out and superimposed on standardized distal femur cross-sections, generating a fracture map for each plane. Injury and fracture characteristics were summarized and compared between fracture patterns. RESULTS: On axial scans, 59 of 63 fractures contained a central intercondylar split from the intercondylar notch to the trochlea. On coronal scans, fracture lines originated at the notch and exited laterally and medially in the supracondylar region, creating a Y-shape. One-third of all fractures contained coronal fracture lines, with most involving the lateral condyle. Based on fracture line orientation and location, fractures were divided into four main fracture pattern types. Type 4 fractures (central split and medial coronal fracture line) were associated with lower average medial fracture height and a lower rate of medial metaphyseal comminution. DISCUSSION: We found that C-type distal femur fractures can present with four main fracture patterns. Most fractures contain a central sagittal intercondylar split, and a high proportion of fractures contain either medial or lateral coronal fracture lines. Fracture pattern was associated with mechanism of injury, presence of medial comminution, and medial fracture line height. Future studies should focus on clinical outcomes and surgical management of these distinct fracture patterns. LEVEL OF EVIDENCE: IV.
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OBJECTIVES: To assess the biomechanical differences between linked and unlinked constructs in young and osteoporotic cadavers in addition to osteoporotic sawbones. METHODS: Intraarticular distal femur fractures with comminuted metaphyseal regions were created in three young matched pair cadavers, three osteoporotic matched pair cadavers, and six osteoporotic sawbones. Precontoured distal femur locking plates were placed in addition to a standardized retrograde nail, with unitized constructs having one 4.5 mm locking screw placed distally through the nail. Nonunitized constructs had seven 4.5 mm locking screws placed through the plate around the nail, with one 5 mm distal interlock placed through the nail alone. Cadaveric specimens were subjected to axial fatigue loads between 150 and 1500 N (R Ratio = 10) with 1 Hx frequency for 10,000 cycles. Sawbones were axially loaded at 50% of the ultimate load for fatigue testing to achieve runout, with testing performed with 30 and 300 N (R Ratio = 10) loads with 1 Hz frequency for 10,000 cycles. RESULTS: In young cadavers, there was no difference in the mean cyclic displacement of the unitized constructs (1.51 ± 0.62mm) compared to the non-unitized constructs (1.34 ± 0.47mm) (Figure 4A), (p = 0.722). In osteoporotic cadavers, there was no difference in the mean cyclic displacement of the unitized constructs (2.46 ± 0.47mm) compared to the non-unitized constructs (2.91 ± 1.49mm) (p =0.639). There was statistically no significant difference in cyclic displacement between the unitized and non-unitized groups in osteoporotic sawbones(p = 0.181). CONCLUSIONS: Linked constructs did not demonstrate increased axial stiffness or decreased cyclical displacement in comparison to unlinked constructs in young cadaveric specimens, osteoporotic cadaveric specimens, or osteoporotic sawbones.
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Clavos Ortopédicos , Placas Óseas , Cadáver , Fracturas del Fémur , Humanos , Fracturas del Fémur/cirugía , Fracturas del Fémur/fisiopatología , Anciano , Femenino , Anciano de 80 o más Años , Fenómenos Biomecánicos , Masculino , Fijación Interna de Fracturas/instrumentación , Fijación Interna de Fracturas/métodos , Adulto , Persona de Mediana Edad , Estrés Mecánico , Osteoporosis/complicaciones , Fracturas Femorales DistalesRESUMEN
INTRODUCTION: This study aimed to assess the safety and efficacy of ambulatory mini-percutaneous nephrolithotomy (mini-PCNL) in a totally tubeless exit (without a nephrostomy tube or an internal stent) and tubeless exit (without a nephrostomy tube but with an internal stent) for the treatment of renal calculi 10-25 mm in size. METHODS: We conducted a retrospective analysis of patients who underwent mini-PCNL at our institution between September 2018 and September 2022. The study included a cohort of 95 patients diagnosed with renal calculi measuring 10-25 mm. All patients underwent a computed tomography (CT) renal colic scan preoperatively, on postoperative day one (POD 1), and at three-month followup. Patient demographics and outcome parameters were recorded, including stone characteristics, operative time, hospital stay, stone-free rate (SFR), complication rates, and subsequent emergency room (ER) visits. Patients were considered stone-free if they had no fragments or residual fragments measuring <4 mm. RESULTS: The median maximum stone diameter was 16 mm (10-25 mm). Twenty-nine patients (30.5%) had multiple renal calculi. The median operative time was 64 (38-135) minutes. Eighty-six patients (90.5%) underwent a totally tubeless procedure, without a nephrostomy tube or an internal stent. All patients were discharged home on the same operative day with a median hospitalization time of six hours. Seven (7.4%) postoperative ER visits were recorded, and two (2.1%) led to hospital readmission. The frequency of grade I, II, and III Clavien-Dindo complications were 18 (18.9%), one (1.1%), and one (1.1%), respectively. The SFR on POD 1 and three-month followup was 73.7% and 92.6%, respectively. None of the patients in the study required retreatment. CONCLUSIONS: Ambulatory tubeless mini-PCNL is a safe and effective treatment option for 10-25 mm renal stones. Experienced institutions can safely adopt ambulatory mini-PCNL as a treatment option without an increased risk of postoperative complications, ER visits, or hospital readmissions.
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Background: Adaptive behavior plays a crucial role in daily functioning, involving a complex interplay between individuals and their environment. In India, the Vineland Social Maturity Scale (VSMS) has been the preferred assessment tool for measuring adaptive behaviors, despite its age of over 85 years. However, periodic evaluation is necessary to ensure its continued relevance. Aim: This study aims to critically evaluate selected items of the Indian version of the VSMS. Materials and Methods: A survey form was developed through a focus group discussion (FGD), comprising 20 items from the Indian adaptation of the VSMS. The form was converted into a Google Form and distributed to medical and rehabilitation specialists across India. The responses were collected, recorded, and analyzed in an Excel sheet. Results: Of the 107 responses received, 14 were incomplete and excluded, leaving 93 complete for analysis. The analysis revealed that less than half of the surveyed items and domains received ratings of disagreement from over a quarter of the respondents concerning their frequency, relevance, and diagnostic value. Conclusion: This study underscores the need for a dynamic approach to defining and assessing adaptive behavior, especially in the Indian context. It highlights the importance of revising existing scales, incorporating technology-related items, and considering societal and cultural norms shifts. While acknowledging its limitations, this research sets the stage for future investigations to gain a more nuanced understanding of adaptive behaviors amidst changing societal dynamics. Ultimately, these efforts aim to develop more comprehensive and relevant assessment tools for adaptive behavior in today's rapidly evolving world.
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BACKGROUND: Multiparametric prostate MRI (mpMRI) is being increasingly adopted for work-up of prostate cancer. For patients selected to omit biopsy, we identified factors associated with repeat MRI, eventual prostate biopsy, and subsequent detection of clinically significant prostate cancer (csPCa, Grade Group ≥2). METHODS: We identified biopsy-naïve men presenting with PSA 2-20 ng/mL (March 2018-June 2021) undergoing initial mpMRI with PIRADS 1-3 lesions who were not selected for biopsy with ≥6 months follow-up. We examined factors associated with repeat mpMRI, progression to biopsy, and subsequent detection of csPCa with univariable and multivariable logistic regression. RESULTS: Of 1494 men, 31% (463/1494) did not pursue biopsy. PSA density (PSAD) ≤ 0.1, prostate health index (PHI) < 55, and PIRADS 1-2 were associated with omission of prostate biopsy. csPCa diagnosis-free survival was 97.6% (326/334) with median follow up of 23.1 months (IQR 15.1-34.6 months). Black race, PSA, PHI, PSA density, and PSA and PHI velocity were significant predictors of undergoing repeat mpMRI (15.6%, 52/334) and subsequent biopsy (8.4%, 28/334). 8 men were subsequently diagnosed with csPCa (N = 7 on prostate biopsy; N = 1 incidentally on holmium enucleation of prostate). All patients diagnosed with csPCa had PIRADS 4-5 on repeat mpMRI. CONCLUSIONS: The subsequent detection rate of csPCa among patients not initially biopsied after mpMRI was low at 2.4%. Decisions to omit biopsy after initial reassuring PHI, PSAD, and mpMRI appear safe with subsequent reassuring serum biomarkers and for cause mpMRI during follow-up.
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Background: Blood flow restriction training (BFRT) is a safe and potentially effective adjunctive therapeutic modality for postoperative rehabilitation related to various knee pathologies. However, there is a paucity of literature surrounding BFRT in high-performance athletes after anterior cruciate ligament reconstruction (ACLR). Purpose: To (1) compare the overall time to return to sports (RTS) in a cohort of National Collegiate Athletic Association (NCAA) Division I athletes who underwent a standardized rehabilitation program either with or without BFRT after ACLR and (2) identify a postoperative time interval for which BFRT has the maximum therapeutic benefit. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 55 student-athletes who underwent ACLR between 2000 and 2023 while participating in NCAA Division I sports at a single institution were included in this study. Athletes were allocated to 1 of 2 groups based on whether they participated in a standardized postoperative rehabilitation program augmented with BFRT (BFRT group; n = 22) or completed the standardized protocol alone (non-BFRT group [control]; n = 33). Our primary outcome measure was time to RTS. The secondary outcome measure was handheld dynamometry quadriceps strength testing at various postoperative time points, converted to a limb symmetry index (LSI). Quadriceps strength was not tested between the BFRT and non-BFRT groups because of the limited amount of data on the control group. Results: The mean age at the date of surgery was 18.59 ± 1.10 years for the BFRT group and 19.45 ± 1.30 years for the non-BFRT group (P = .011), and the mean RTS time was 409 ± 134 days from surgery for the BFRT group and 332 ± 100 days for the non-BFRT cohort (P = .047). For the BFRT group, the mean quadriceps strength LSI increased by 0.67% (95% CI, 0.53%-0.81%) for every week of rehabilitation, and there was a significantly positive rate of change in quadriceps strength in weeks 13-16 compared with weeks 9-12 (ΔLSI, 8.22%; P < .001). Conclusion: In elite NCAA Division I athletes, a statistically significant delay was observed in RTS with BFRT compared with standardized physical therapy alone after undergoing ACLR. There also appeared to be an early window during the rehabilitation period where BFRT had a beneficial impact on quadriceps strength.
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The National Comprehensive Cancer Network (NCCN) very low risk (VLR) category for prostate cancer (PCa) represents clinically insignificant disease, and detection of VLR PCa contributes to overdiagnosis. Greater use of magnetic resonance imaging (MRI) and biomarkers before patient selection for prostate biopsy (PBx) reduces unnecessary biopsies and may reduce the diagnosis of clinically insignificant PCa. We tested a hypothesis that the proportion of VLR diagnoses has decreased with greater use of MRI-informed PBx using data from our 11-hospital system. From 2018 to 2023, 351/3197 (11%) men diagnosed with PCa met the NCCN VLR criteria. The proportion of VLR diagnoses did not change from 2018 to 2023 (p = 0.8) despite an increase in the use of MRI-informed PBx (from 49% to 82%; p < 0.001). Of patients who underwent combined systematic and targeted PBx and were diagnosed with VLR disease, cancer was found in systematic PBx regions in 79% of cases and in targeted PBx regions in 31% of cases. When performing both systematic and targeted PBx, prebiopsy MRI-based risk calculators could limit VLR diagnosis by 41% using a risk threshold of >5% for Gleason grade group ≥3 PCa to recommend biopsy; the reduction would be 77% if performing targeted PBx only. These findings suggest that VLR disease continues to account for a significant minority of PCa diagnoses and could be limited by targeted PBx and risk stratification calculators. PATIENT SUMMARY: We looked at recent trends for the diagnosis of very low-risk (VLR) prostate cancer. We found that VLR cancer still seems to be frequently diagnosed despite the use of MRI (magnetic resonance imaging) scans before biopsy. The use of risk calculators to identify men who could avoid biopsy and/or biopsy only for lesions that are visible on MRI could reduce the overdiagnosis of VLR prostate cancer.
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Background Menopause is a physiological state that occurs in all women and refers to the halt of the reproductive phase. The cessation of the reproductive phase occurs through various stages and presents different symptoms such as hot flashes, night sweats, insomnia, anxiety, depression, and irritability. Such pre- and post-menopausal symptoms may affect the daily activities and production capacities of women, impacting the quality of life (QoL) of women. Hormone replacement therapy (HRT) is primarily used to manage menopausal symptoms. However, various side effects have been reported related to HRT. Therefore, women are choosing alternative medicine such as Ayurveda that can benefit them with less or no adverse effects. Shatavari (Asparagus racemosus) is known in Ayurveda as an effective medicinal plant source for various women's health remedies since ancient times. This study aimed to evaluate the safety and efficacy of the Ayurvedic Shatavari formulation on menopausal symptoms compared to the placebo. Methodology This is a randomized, double-blinded, multicenter, placebo-controlled, clinical study. Altogether, 70 patients were randomized to two groups, i.e., the test group (active group) and the placebo group (microcrystalline cellulose), with 35 participants in each group. Results The study outcomes showed a positive and significant effect of the active test ingredient over the placebo in terms of reduction in hot flashes, night sweats, insomnia, anxiety, nervousness, vaginal dryness, and loss of libido. The Utian QoL improved significantly in the test group compared to the placebo group. No significant adverse events were recorded in the test group, suggesting the safety of this formulation. Conclusions The test compound could be a safe alternative to modern drugs. The findings of this study support the traditional use of Shatavari. Further clinical and pharmacological studies with longer duration and larger and more diverse sample sizes are required to understand the generalized effect of Shatavari root extract in menopausal women.
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BACKGROUND: We previously reported our phase Ib trial, testing the safety, tolerability, and efficacy of T-DM1 + neratinib in HER2-positive metastatic breast cancer patients. Patients with ERBB2 amplification in ctDNA had deeper and more durable responses. This study extends these observations with in-depth analysis of molecular markers and mechanisms of resistance in additional patients. METHODS: Forty-nine HER2-positive patients (determined locally) who progressed on-treatment with trastuzumab + pertuzumab were enrolled in this phase Ib/II study. Mutations and HER2 amplifications were assessed in ctDNA before (C1D1) and on-treatment (C2D1) with the Guardant360 assay. Archived tissue (TP0) and study entry biopsies (TP1) were assayed for whole transcriptome, HER2 copy number, and mutations, with Ampli-Seq, and centrally for HER2 with CLIA assays. Patient responses were assessed with RECIST v1.1, and Molecular Response with the Guardant360 Response algorithm. RESULTS: The ORR in phase II was 7/22 (32%), which included all patients who had at least one dose of study therapy. In phase I, the ORR was 12/19 (63%), which included only patients who were considered evaluable, having received their first scan at 6 weeks. Central confirmation of HER2-positivity was found in 83% (30/36) of the TP0 samples. HER2-amplified ctDNA was found at C1D1 in 48% (20/42) of samples. Patients with ctHER2-amp versus non-amplified HER2 ctDNA determined in C1D1 ctDNA had a longer median progression-free survival (PFS): 480 days versus 60 days (P = 0.015). Molecular Response scores were significantly associated with both PFS (HR 0.28, 0.09-0.90, P = 0.033) and best response (P = 0.037). All five of the patients with ctHER2-amp at C1D1 who had undetectable ctDNA after study therapy had an objective response. Patients whose ctHER2-amp decreased on-treatment had better outcomes than patients whose ctHER2-amp remained unchanged. HER2 RNA levels show a correlation to HER2 CLIA IHC status and were significantly higher in patients with clinically documented responses compared to patients with progressive disease (P = 0.03). CONCLUSIONS: The following biomarkers were associated with better outcomes for patients treated with T-DM1 + neratinib: (1) ctHER2-amp (C1D1) or in TP1; (2) Molecular Response scores; (3) loss of detectable ctDNA; (4) RNA levels of HER2; and (5) on-treatment loss of detectable ctHER2-amp. HER2 transcriptional and IHC/FISH status identify HER2-low cases (IHC 1+ or IHC 2+ and FISH negative) in these heavily anti-HER2 treated patients. Due to the small number of patients and samples in this study, the associations we have shown are for hypothesis generation only and remain to be validated in future studies. Clinical Trials registration NCT02236000.
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Ado-Trastuzumab Emtansina , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Mama , Quinolinas , Receptor ErbB-2 , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/metabolismo , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Ado-Trastuzumab Emtansina/uso terapéutico , Persona de Mediana Edad , Quinolinas/uso terapéutico , Quinolinas/administración & dosificación , Anciano , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , ADN Tumoral Circulante/genética , ADN Tumoral Circulante/sangre , Biomarcadores de Tumor/genética , Mutación , Anciano de 80 o más Años , Trastuzumab/uso terapéutico , Trastuzumab/administración & dosificación , Resultado del Tratamiento , Metástasis de la NeoplasiaRESUMEN
BACKGROUND: The management of elderly acetabular fractures is complex, with high rates of conversion total hip arthroplasty (THA) after open reduction and internal fixation (ORIF), but potentially higher rates of complications after acute THA. METHODS: The California Office of Statewide Health Planning and Development database was queried between 2010 and 2017 for all patients aged 60 years or older who sustained a closed, isolated acetabular fracture and underwent ORIF, THA, or a combination. Chi-square tests and Student t tests were used to identify demographic differences between groups. Multivariate regression was used to evaluate predictors of 30-day readmission and 90-day complications. Kaplan-Meier (KM) survival analysis and Cox proportional hazards model were used to estimate the revision surgery-free survival (revision-free survival [RFS]), with revision surgery defined as conversion THA, revision ORIF, or revision THA. RESULTS: A total of 2,184 surgically managed acetabular fractures in elderly patients were identified, with 1,637 (75.0%) undergoing ORIF and 547 (25.0%) undergoing THA with or without ORIF. Median follow-up was 295 days (interquartile range, 13 to 1720 days). 99.4% of revisions following ORIF were for conversion arthroplasty. Unadjusted KM analysis showed no difference in RFS between ORIF and THA (log-rank test P = 0.27). RFS for ORIF patients was 95.1%, 85.8%, 78.3%, and 71.4% at 6, 12, 24 and 60 months, respectively. RFS for THA patients was 91.6%, 88.9%, 87.2%, and 78.8% at 6, 12, 24 and 60 months, respectively. Roughly 50% of revisions occurred within the first year postoperatively (49% for ORIF, 52% for THA). In propensity score-matched analysis, there was no difference between RFS on KM analysis ( P = 0.22). CONCLUSIONS: No difference was observed in medium-term RFS between acute THA and ORIF for elderly acetabular fractures in California. Revision surgeries for either conversion or revision THA were relatively common in both groups, with roughly half of all revisions occurring within the first year postoperatively. LEVEL OF EVIDENCE: III.
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Acetábulo , Artroplastia de Reemplazo de Cadera , Fijación Interna de Fracturas , Fracturas Óseas , Reducción Abierta , Reoperación , Humanos , Reoperación/estadística & datos numéricos , Anciano , Artroplastia de Reemplazo de Cadera/efectos adversos , Acetábulo/lesiones , Acetábulo/cirugía , Femenino , Masculino , Fijación Interna de Fracturas/métodos , Fijación Interna de Fracturas/efectos adversos , Fracturas Óseas/cirugía , Anciano de 80 o más Años , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios RetrospectivosRESUMEN
Uncompetitive inhibition is an effective strategy for suppressing dysregulated enzymes and their substrates, but discovery of suitable ligands depends on often-unavailable structural knowledge and serendipity. Hence, despite surging interest in mass spectrometry-based target identification, proteomic studies of substrate-dependent target engagement remain sparse. Herein, we describe the Thermal Shift Assay with ATP and RNA (TSAR) as a template for proteome-wide discovery of substrate-dependent ligand binding. Using proteomic thermal shift assays, we show that simple biochemical additives can facilitate detection of target engagement in native cell lysates. We apply our approach to rocaglates, a family of molecules that specifically clamp RNA to eukaryotic translation initiation factor 4A (eIF4A), DEAD-box helicase 3X (DDX3X), and potentially other members of the DEAD-box (DDX) family of RNA helicases. To identify unexpected interactions, we optimized a target class-specific thermal denaturation window and evaluated ATP analog and RNA probe dependencies for key rocaglate-DDX interactions. We report novel DDX targets of the rocaglate clamping spectrum, confirm that DDX3X is a common target of several widely studied analogs, and provide structural insights into divergent DDX3X affinities between synthetic rocaglates. We independently validate novel targets of high-profile rocaglates, including the clinical candidate Zotatifin (eFT226), using limited proteolysis-mass spectrometry and fluorescence polarization experiments. Taken together, our study provides a model for screening uncompetitive inhibitors using a systematic chemical-proteomics approach to uncover actionable DDX targets, clearing a path towards characterization of novel molecular clamps and associated RNA helicase targets.
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There are several cellular and acellular structural barriers associated with the brain interfaces, which include the dura, the leptomeninges, the perivascular space and the choroid plexus epithelium. Each structure is enriched by distinct myeloid populations, which mainly originate from erythromyeloid precursors (EMP) in the embryonic yolk sac and seed the CNS during embryogenesis. However, depending on the precise microanatomical environment, resident myeloid cells differ in their marker profile, turnover and the extent to which they can be replenished by blood-derived cells. While some EMP-derived cells seed the parenchyma to become microglia, others engraft the meninges and become CNS-associated macrophages (CAMs), also referred to as border-associated macrophages (BAMs), e.g., leptomeningeal macrophages (MnMΦ). Recent data revealed that MnMΦ migrate into perivascular spaces postnatally where they differentiate into perivascular macrophages (PvMΦ). Under homeostatic conditions in pathogen-free mice, there is virtually no contribution of bone marrow-derived cells to MnMΦ and PvMΦ, but rather to macrophages of the choroid plexus and dura. In neuropathological conditions in which the blood-brain barrier is compromised, however, an influx of bone marrow-derived cells into the CNS can occur, potentially contributing to the pool of CNS myeloid cells. Simultaneously, resident CAMs may also proliferate and undergo transcriptional and proteomic changes, thereby, contributing to the disease outcome. Thus, both resident and infiltrating myeloid cells together act within their microenvironmental niche, but both populations play crucial roles in the overall disease course. Here, we summarize the current understanding of the sources and fates of resident CAMs in health and disease, and the role of the microenvironment in influencing their maintenance and function.
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Macrófagos , Proteómica , Ratones , Animales , Macrófagos/patología , Sistema Nervioso Central/patología , Microglía , MeningesRESUMEN
PURPOSE: Ankle arthrodesis is a mainstay of surgical management for ankle arthritis. Accurately risk-stratifying patients who undergo ankle arthrodesis would be of great utility. There is a paucity of accurate prediction models that can be used to pre-operatively risk-stratify patients for ankle arthrodesis. We aim to develop a predictive model for major perioperative complication or readmission after ankle arthrodesis. METHODS: This is a retrospective cohort study of adult patients who underwent ankle arthrodesis at any non-federal California hospital between 2015 and 2017. The primary outcome is readmission within 30 days or major perioperative complication. We build logistic regression and ML models spanning different classes of modeling approaches, assessing discrimination and calibration. We also rank the contribution of the included variables to model performance for prediction of adverse outcomes. RESULTS: A total of 1084 patients met inclusion criteria for this study. There were 131 patients with major complication or readmission (12.1%). The XGBoost algorithm demonstrates the highest discrimination with an area under the receiver operating characteristic curve of 0.707 and is well-calibrated. The features most important for prediction of adverse outcomes for the XGBoost model include: diabetes, peripheral vascular disease, teaching hospital status, morbid obesity, history of musculoskeletal infection, history of hip fracture, renal failure, implant complication, history of major fracture. CONCLUSION: We report a well-calibrated algorithm for prediction of major perioperative complications and 30-day readmission after ankle arthrodesis. This tool may help accurately risk-stratify patients and decrease likelihood of major complications.
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Artroplastia de Reemplazo de Tobillo , Fracturas Óseas , Adulto , Humanos , Artroplastia de Reemplazo de Tobillo/efectos adversos , Articulación del Tobillo/cirugía , Readmisión del Paciente , Estudios Retrospectivos , Tobillo/cirugía , Artrodesis/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Fracturas Óseas/cirugía , Algoritmos , Resultado del TratamientoRESUMEN
INTRODUCTION: We evaluated the impact of age on perioperative morbidity and clinical outcomes in patients undergoing GreenLight laser prostatectomy for benign prostatic hyperplasia (BPH). METHODS: We conducted a retrospective study of prospectively collected data from individuals who underwent GreenLight laser prostatectomy from May 2018 to July 2022. Patient demographics and outcome measures were recorded, including indications for the procedure and American Society of Anesthesiology (ASA) scores. All patients had postoperative followup visits at one, three, six, and 12 months. Our evaluation included the International Prostate Symptom Score (IPSS ), quality of life (QoL) assessment, maximum urinary flow rate (Qmax), postvoid residual volume (PVR), and catheter-free status. RESULTS: One-hundred-sixty-eight males who underwent GreenLight laser prostatectomy were included. The non-octogenarian group consisted of 111 patients and the octogenarian group comprised 57 individuals. Based on ASA scores, most octogenarians were deemed high-risk (ASA III: 91.2%), while over half of non-octogenarians were lower-risk (ASA II: 53.2%) (p<0.001). Intraoperative parameters, including operative time, vaporization time, lasing time, and energy did not differ significantly between groups. There was no difference in the proportion of intraoperative complications between non-octogenarians and octogenarians (0.9% vs. 3.5%). Postoperative complications were not statistically significant between the two groups (p=0.608). There was also no observed difference in the proportion of patients requiring readmission (p=0.226) or retreatment (p=1.0). CONCLUSIONS: GreenLight laser prostatectomy is a safe and effective treatment for BPH regardless of age. It provides similar surgical and functional outcomes as younger men while maintaining the QoL of octogenarians.
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The genus Phyllanthus belongs to one of the largest plant families, the Phyllantaceae (L.). Phyllanthus niruri is an annual perennial herb that grows in tropical Asia, America, China, and the islands of the Indian Ocean. Numerous alkaloids, steroids, flavonoids, lignans, coumarins, polyphenols, and lipids are present in Phyllanthus. The effects of plants have been studied for a variety of purposes, including their antioxidant (Giribabu et al., Evid Based Complement Alternat Med, 2014), anti-inflammatory (Porto et al., Revista Brasileira de Pharmacognosy, 2013), antinociceptive (Sathisha et al., Indian Drugs, 2009), analgesic (Mostofa et al., BMC Complement Altern Med, 2017), antiulcer (Mali et al., Biomed Aging Pathol, 2011), antiarthritic (Obidike and Salawu, Planta Medica, 2010), antiplasmodial (Shilpa et al., Environ Dis, 2018), immunomodulatory (Manikkoth et al., Anticonvulsant activity of Phyllanthus amarus in experimental animal models), anticonvulsant (Wasnik et al., Int J Pharm Sci Rev Res, 2014), antidepressant (Venkateswaran et al., Effects of an extract from Phyllanthus niruri on hepatitis B and woodchuck hepatitis viruses: In vitro and in vivo studies (antiviral agent/Marmota monax/DNA polymerase/hepatitis B surface antigen/woodchuck hepatitis surface antigen). In Hepatitis B and The Prevention of Primary Cancer of The Liver: Selected Publications of Baruch S Blumberg, pp 535-539), antiviral (Venkateswaran et al., Effects of an extract from Phyllanthus niruri on hepatitis B and woodchuck hepatitis viruses: In vitro and in vivo studies (antiviral agent/Marmota monax/DNA polymerase/hepatitis B surface antigen/woodchuck hepatitis surface antigen). In Hepatitis B and The Prevention of Primary Cancer of The Liver: Selected Publications of Baruch S Blumberg, pp 535-539), antitumor (Sharma et al., Asian Pac J Cancer Prev, 2009), hyperlipidemia (Khanna et al., J Ethnopharmacol, 2002), and antifertility (Ezeonwu, Inquiries J, 2011). For additional docking investigations with distinct proteins, the leaf chemicals are assessed, that is, the crystal structure of serine protease hepsin in complex with inhibitor [PDB ID:5 CE1] for antiviral activity human topoisomerase II beta in complex with DNA and etoposide [PDB ID:3QX3] and crystal structure of E. coli GyraseB 24 kDa in complex with 4-(4-bromo-1H-pyrazol-1-yl)-6-[(ethylcarbamoyl)amino]-N-(pyridin-3-yl) pyridine-3-carboxamide [PDB ID: 6F86] for antibacterial activity and have been selected. To evaluate the in silico results and grading of virtual screening, or molecular docking, ritonavir antiviral activity and ampicillin for antibacterial activity were used as a benchmark.
Asunto(s)
Hepatitis B , Neoplasias Hepáticas , Phyllanthus , Animales , Humanos , Extractos Vegetales/uso terapéutico , Antígenos de Superficie de la Hepatitis B , Marmota , Simulación del Acoplamiento Molecular , Phyllanthus/química , Anticonvulsivantes/uso terapéutico , Escherichia coli , Hepatitis B/tratamiento farmacológico , Antibacterianos/uso terapéutico , Antivirales/farmacología , Antivirales/uso terapéutico , Hojas de la Planta , ADN Polimerasa Dirigida por ADN , Neoplasias Hepáticas/tratamiento farmacológico , Antígenos de Superficie/uso terapéuticoRESUMEN
Objectives: Implant prominence after ulnar fracture fixation may be mitigated by the use of lower profile plates. The biomechanical strength and stability of 2.7-mm and 3.5-mm locking compression plates for fixation were compared. Methods: Two fracture conditions, transverse (N = 10) and oblique (N = 10), were evaluated in an in vitro study. Half of the specimens for each condition were fixed with 2.7-mm plates and the other half with 3.5-mm plates, all fixed with conventional dynamic compression mechanisms. Specimens were loaded under ±2 Nm of cyclic axial torsion, then under 10 Nm of cyclic cantilever bending, and bending to failure. Interfragmentary motion and strain were analyzed to determine construct stability as a function of fracture pattern and plate size. Results: Interfragmentary motion was significantly larger in all constructs fixed with 2.7-mm plates, compared with 3.5-mm plates (P < 0.01). The 2.7-mm constructs with transverse fractures had the greatest motion, ranging between 5° and 10° under axial rotation and 5.0-6.0 mm under bending. Motions were the lowest for 3.5-mm constructs with oblique fractures, ranging between 3.2 and 4.2 mm under bending and 2°-3.5° for axial rotation. For oblique fractures, the bending moment at ultimate failure was 31.4 ± 3.6 Nm for the 2.7-mm constructs and 10.0 ± 1.9 Nm for 3.5-mm constructs (P < 0.01). Similarly, for transverse fractures, the bending moment was 17.9 ± 4.0 Nm for the 2.7-mm constructs and 9.7 ± 1.3 Nm for the 3.5-mm constructs (P < 0.01). Conclusions: Although 3.5-mm plates were more effective at reducing fracture motion, they were consistently associated with refracture at the distal-most screw hole under load to failure. By contrast, 2.7-mm plates plastically deformed despite excessive loads, potentially avoiding a subsequent fracture. Level of Evidence: Level V.