SAUR63 stimulates cell growth at the plasma membrane.

In plants, regulated cell expansion determines organ size and shape. Several members of the family of redundantly acting Small Auxin Up RNA (SAUR) proteins can stimulate plasma membrane (PM) H+-ATPase proton pumping activity by inhibiting PM-associated PP2C.D phosphatases, thereby increasing the PM electrochemical potential, acidifying the apoplast, and stimulating cell expansion. Similarly, Arabidopsis thaliana SAUR63 was able to increase growth of various organs, antagonize PP2C.D5 phosphatase, and increase H+-ATPase activity. Using a gain-of-function approach to bypass genetic redundancy, we dissected structural requirements for SAUR63 growth-promoting activity. The divergent N-terminal domain of SAUR63 has a predicted basic amphipathic α-helix and was able to drive partial PM association. Deletion of the N-terminal domain decreased PM association of a SAUR63 fusion protein, as well as decreasing protein level and eliminating growth-promoting activity. Conversely, forced PM association restored ability to promote H+-ATPase activity and cell expansion, indicating that SAUR63 is active when PM-associated. Lipid binding assays and perturbations of PM lipid composition indicate that the N-terminal domain can interact with PM anionic lipids. Mutations in the conserved SAUR domain also reduced PM association in root cells. Thus, both the N-terminal domain and the SAUR domain may cooperatively mediate the SAUR63 PM association required to promote growth.

Unified approach for tolerance analysis, synthesis, and compensator selection.

Tolerancing is a necessary task for practical designs. The system Jacobian is utilized here for the three sub-tasks of tolerancing. The first is tolerance analysis, which is evaluation of the perturbed system. Second is tolerance allocation, also known as tolerance budgeting and more widely known as error budgeting. The automatic allocation of tolerances is tolerance synthesis. The algorithm described accomplishes this by fitting an orthotope inside an ellipsoid. Third is compensator selection. Metrics are presented that correlate with the looseness of the allocated tolerances and hence with the effectiveness of the compensator set, thus enabling identification of the most optimum combination of compensators.

Fabricating Flaps in the Forearm Prior to Tracheal Reconstruction.

Background The process of reconstruction of tracheal defects is complex and still not optimum. Options range from using staged reconstructions, combining flaps with autologous or alloplastic implants, as well as use of tissue-engineered constructs combined with vascularized tissues which are lined with cell cultures. Staged reconstructions using prelaminated epithelium, and prefabricated flaps, help in reconstruction of this complex structure. Prefabricating the flap at a different site allows for integration of the tissues prior to its transfer. Method This article reports two patients planned for tracheal reconstruction for the purpose of advanced papillary carcinoma of the thyroid invading the trachea. Staged reconstruction using a prefabricated radial artery forearm flap (RAFF) and split rib cartilage was performed. In the second patient, a young girl, a similar construct of the RAFF, prelaminated with buccal mucosa, was performed. However, in the latter case, an intraoperative decision by the head and neck team to limit excision of the trachea sparing the mucosa was taken; the reconstruct in the forearm was redundant and needed to be discarded, replacing the defect with a free superficial circumflex iliac artery perforator (SCIP) flap. Result At 3 years follow-up, both the patients are free of disease, with the construct serving its purpose in the older female.

Redefining adequate margins in oral squamous cell carcinoma: outcomes from close and positive margins.

PURPOSE: Adequacy of surgical margins impacts outcomes in oral cancer. We sought to determine whether close and positive margins have different outcomes in patients with oral cancer. METHODS: Retrospective data from 612 patients with oral carcinoma were analyzed for the effect of margin status on locoregional recurrence-free survival (LRFS), disease-free survival (DFS) and overall survival (OS). RESULTS: A total of 90 cases (14.7%) had close margins and 26 patients (4.2%) had positive margins. Recurrences were documented in 173 patients (28%), of which 137 (22% of the study sample) were locoregional, and 164 patients (27%) had died. Among patients with close or positive margins, a cutoff of 1 mm optimally separated LRFS (adjusted p = 0.0190) and OS curves (adjusted p = 0.0168) whereas a cutoff of 2 mm was sufficient to significantly separate DFS curves (adjusted p = 0.0281). CONCLUSIONS: Patients with oral carcinoma with positive margins (< 1 mm) had poorer outcomes compared to those with close margins (1-5 mm) in terms of LRFS, DFS and OS. There is a suggestion that a cutoff of < 2 mm might provide slightly more separation for DFS.

Optical tolerancing and principal component analysis.

This work explores the use of linear principal component analysis (PCA) during an optical design's tolerancing analysis. Chapman et al. [Proc. SPIE3331, 102 (1998)PSISDG0277-786X] have shown the usefulness of the singular value decomposition in realizing an alignment algorithm for a system. This paper explores some insights that can be gained from performing PCA on the Monte Carlo data set obtained during the tolerancing step and comparing it with the singular components of the Jacobian (sensitivity matrix) of the system.

The Efficacy of WALANT Technique in the Management of Distal End Radius Fracture - A Case Series.

Introduction: To improve hemostasis and visibility, a tourniquet was used throughout the majority of hand and wrist procedures, despite the fact that patient experience unnecessary and excruciating pain from the tourniquet. The more current method known as wide-awake local anesthesia without tourniquet (WALANT) enables intraoperative function evaluation while the patient is completely conscious. Materials and Methods: Individuals with displaced distal radius fractures that required surgery and isolated, non-concomitant injuries requiring spinal or general anesthesia were considered for WALANT technique. In our study, five patients underwent dorsal plate fixation and five patients underwent volar plate fixation. Patients receiving dorsal plate fixation required definite dorsal buttress to prevent radiocarpal dislocation. Conclusion: The WALANT technique is a simple, reliable, and effective anesthetic method for internal fixation and open reduction of distal radius fractures. Since a tourniquet is not necessary, the patient is protected from the discomfort and risks associated with one.

Contrasting clinical outcomes and socio-economic impact of young versus elderly-onset oral squamous cell carcinoma, a novel health economic analysis.

OBJECTIVES: The incidence of young-onset oral squamous cell carcinoma (OSCC) is growing, even among non-smokers/drinkers. The effects of adverse histopathological features on long-term oncologic outcomes between the young and old are controversial and confounded by significant heterogeneity. Few studies have evaluated the socio-economic impact of premature mortality from OSCC. Our study seeks to quantify these differences and their economic impact on society. MATERIALS AND METHODS: Four hundred and seventy-eight young (<45 years) and 1660 old patients (≥45 years) with OSCC were studied. Logistic regression determined predictors of recurrence and death. Survival analysis was calculated via the Kaplan-Meier method. A separate health economic analysis was conducted for India and Singapore. Years of Potential Productive Life Lost (YPPLL) were estimated with the Human Capital Approach, and premature mortality cost was derived using population-level data. RESULTS: Adverse histopathological features were seen more frequently in young OSCC: PNI (42.9% vs. 35%, p = 0.002), LVI (22.4% vs. 17.3%, p = 0.013) and ENE (36% vs. 24.5%, p < 0.001). Although 5-year OS/DSS were similar, the young cohort had received more intensive adjuvant therapy (CCRT 26.9% vs. 16.6%, p < 0.001). Among Singaporean males, the premature mortality cost per death was US $396,528, and per YPPLL was US $45,486. This was US $397,402 and US $38,458 for females. Among Indian males, the premature mortality cost per death was US $30,641, and per YPPLL was US $595. This was US $ 21,038 and US $305 for females. CONCLUSION: Young-onset OSCC is an aggressive disease, mitigated by the ability to receive intensive adjuvant treatment. From our loss of productivity analysis, the socio-economic costs from premature mortality are substantial. Early cancer screening and educational outreach campaigns should be tailored to this cohort. Alongside, more funding should be diverted to genetic research, developing novel biomarkers and improving the efficacy of adjuvant treatment in OSCC.

Unlocking Therapeutic Potential of Poly(Adenosine Diphosphate Ribose) Polymerase (PARP) Inhibitors in Metastatic Breast Cancer With BRCA Gene Mutations: A Narrative Review.

Breast cancer (BC), a significant global health concern, impacts millions of women worldwide. A key genetic factor in this disease is the presence of BReast CAncer gene (BRCA) mutations, which increase susceptibility to BC. This narrative review explores the crucial role of poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors in treating metastatic BC in individuals with BRCA gene mutations. In BRCA mutation carriers, these inhibitors induce synthetic lethality, leading to cell death due to the accumulation of lethal DNA breaks. Clinical trials have demonstrated the effectiveness of PARP inhibitors, such as olaparib and talazoparib, in extending progression-free survival and response rates, especially in patients without prior chemotherapy. Moreover, this review discusses combination therapies, where PARP inhibitors are combined with cytostatic drugs like platinum-based chemotherapy. Some studies show the synergy of these approaches, even in patients without homologous recombination deficiency. In summary, PARP inhibitors offer hope for improving outcomes in metastatic BC patients with BRCA gene mutations. As research advances, PARP inhibitors continue to hold promise in the fight against BC.

Navigating the Immune Challenge in Glioblastoma: Exploring Immunotherapeutic Avenues for Overcoming Immune Suppression.

Glioblastoma multiforme (GBM) is a primary brain tumor known for its short survival time, typically 14-18 months from diagnosis to fatality. Managing GBM poses significant challenges due to factors like the formidable blood-brain barrier, the immunosuppressive conditions within GBM, and the intricacies of surgical procedures. Currently, the typical treatment for GBM combines surgical procedures, radiation therapy, and chemotherapy using temozolomide. Unfortunately, this conventional approach has not proven effective in substantially extending the lives of GBM patients. Consequently, researchers are exploring alternative methods for GBM management. One promising avenue receiving attention in recent years is immunotherapy. This approach has successfully treated cancer types like non-small cell lung cancer and blood-related malignancies. Various immunotherapeutic strategies are currently under investigation for GBM treatment, including checkpoint inhibitors, vaccines, chimeric antigen receptor (CAR) T-cell therapy, and oncolytic viruses. A comprehensive review of 26 high-quality studies conducted over the past decade, involving thorough searches of databases such as PubMed and Google Scholar, has been conducted. The findings from this review suggest that while immunotherapeutic strategies show promise, they face significant limitations and challenges in practical application for GBM treatment. The study emphasizes the importance of combining diverse approaches, customizing treatments for individual patients, and ongoing research efforts to improve GBM patients' outlook.

A retrospective analysis of the factors associated with increased risk of readmission within 30 days after primary transurethral resection of bladder tumor.

Background: Transurethral resection of bladder tumor (TURBT) is associated with perioperative morbidity of 5% to 10%, which can lead to unplanned readmissions. In this study, we aimed to identify the factors that lead to an increased risk of unplanned readmissions within 30 days of primary TURBT. Materials and methods: A retrospective study was conducted to identify patients who underwent primary TURBT at our institute from 2011 to 2019. Clinical and demographic factors, history of smoking, antiplatelet drugs intake, comorbidities, tumor size (<3 or >3 cm), multifocality, and histopathological type were abstracted. Patients who were readmitted were identified, and reasons for admission were recorded. Results: A total of 435 patients were identified. The median age of the patients was 66 years. From 378 male patients (86.9%), 110 (25.3%) and 37 (8.5%) had a history of smoking and antiplatelet agents intake, respectively. In the cohort, 166 patients (38.2%) were diabetic, 239 (54.9%) were hypertensive, 72 (16.6%) had chronic obstructive pulmonary disease, and 78 (7.9%) had hypothyroidism. A total of 206 patients (47.4%) had a tumor >3 cm; multifocality was seen in 140 (32.2%) patients, whereas muscle invasive tumors were present in 161 patients (37%). A total of 22 patients (5.06%) had readmissions within 30 days, with hematuria being the most common etiology. On univariate and multivariate analyses, a history of smoking (p = 0.006 and p = 0.008, respectively) or antiplatelet agents intake (p < 0.001 and p < 0.001, respectively) was significantly associated with increased unplanned readmission. Conclusions: Our study revealed smoking and antiplatelet agents intake as factors leading to an increased risk of unplanned readmissions.

Subcategorization of Perineural Invasion and Its Impact on Survival in Patients with Oral Squamous Cell Carcinoma.

BACKGROUND: Perineural invasion (PNI) is  recognized as a poor prognostic factor in oral squamous cell carcinoma (OSCC). However, the prognostic significance of further histologic  subcategorization of PNI is inconclusive. In this study, we determined the prognostic relevance of histologic subcategories of PNI and their correlation with the presence of other clinical and pathological parameters METHODS: This is a retrospective study of 207 homogeneously treated OSCC patients with histologically documented PNI from a single center. Univariate and multivariate survival outcomes, namely, local recurrence-free survival (LRFS), disease-free survival (DFS), and overall survival (OS) of patients with various subcategories of PNI,namely- number of foci, size of the involved nerve, extratumoral or intratumoral extent, and intraneural or perineural location-were determined. RESULTS: Within the histologic subcategories of PNI, tongue primary and presence of lymph node metastasis correlated significantly with the number of nerves involved with PNI. Larger size of involved nerve correlated with advanced tumor stage. Number of foci, extent, and location of PNI were not prognostically significant except size of the involved nerve which showed an inverse correlation with disease outcome as involvement of larger nerves displayed better outcomes in terms of DFS and LRFS but not of OS on multivariate analysis. Addition of adjuvant chemotherapy to radiotherapy emerged as a significant predictor of improved LRFS, DFS, and OS. CONCLUSIONS: Histologic subcategorization of PNI did not have prognostic relevance in our study. Involvement of even small nerves was associated with poor prognosis. Addition of chemoradiation was seen to improve prognosis.

Effectiveness of Transesophageal Echocardiography in Preventing Thromboembolic Complications Before Cardioversion: A Narrative Review.

Atrial fibrillation (AFib) is one of the most prevalent irregular heartbeats that doctors encounter. Clinicians typically pursue two main approaches for treatment, namely, controlling the heart rate and managing the heart rhythm. Under the rhythm control approach, AFib is addressed through cardioversion, which is achieved either with medications termed pharmacological cardioversion (PCV) or via an electrical shock termed electric cardioversion (ECV). While ECV proves instrumental in AFib management, it carries its own risk factors, potentially leading to blood clot-related complications such as embolic strokes. To counteract this potential downside, a well-established strategy involves the utilization of transesophageal echocardiography (TEE) to identify possible embolic sources before initiating cardioversion. The goal of this systematic review is to highlight the role of TEE in preempting embolic occurrences following ECV during the management of AFib. After conducting a thorough search of databases, namely, PubMed, PubMed Central, and Medline, a total of 36 studies were selected for this review article. Following a comprehensive evaluation of these studies, it was concluded that TEE plays a pivotal role in preventing thromboembolic complications during ECV for AFib. However, it is important to note that further research is needed to delve deeper into this matter. While existing evidence underscores its efficacy, additional investigation is needed to address this subject matter comprehensively.