Telomeres maintain genomic integrity in normal cells, and their progressive shortening during successive cell divisions induces chromosomal instability. In the large majority of cancer cells, ...telomere length is maintained by telomerase. Thus, telomere length and telomerase activity are crucial for cancer initiation and the survival of tumors. Several pathways that regulate telomere length have been identified, and genome-scale studies have helped in mapping genes that are involved in telomere length control. Additionally, genomic screening for recurrent human telomerase gene hTERT promoter mutations and mutations in genes involved in the alternative lengthening of telomeres pathway, such as ATRX and DAXX, has elucidated how these genomic changes contribute to the activation of telomere maintenance mechanisms in cancer cells. Attempts have also been made to develop telomere length- and telomerase-based diagnostic tools and anticancer therapeutics. Recent efforts have revealed key aspects of telomerase assembly, intracellular trafficking and recruitment to telomeres for completing DNA synthesis, which may provide novel targets for the development of anticancer agents. Here, we summarize telomere organization and function and its role in oncogenesis. We also highlight genomic mutations that lead to reactivation of telomerase, and mechanisms of telomerase reconstitution and trafficking that shed light on its function in cancer initiation and tumor development. Additionally, recent advances in the clinical development of telomerase inhibitors, as well as potential novel targets, will be summarized.
Purpose
The purpose of this paper is to have an overview of how Indian institutions offering undergraduate architecture programs have responded to the pandemic situation. It seeks to appraise the ...alternative approaches adopted for teaching-learning, communication, assignment and evaluation and assess their effectiveness for progressive improvisations or integration with pedagogy. The paper articulates a view on the suitability of online teaching for architecture education in India, on basis of educators' experiences of teaching during the pandemic.
Design/methodology/approach
An online survey was conducted for obtaining primary data from the educators given the paucity of information. The questions elicited structured information on aspects of the transition process, IT/online platform and tools, the efficacy of online teaching-learning and trajectory of blended learning.
Findings
All institutions managed the transition to online teaching without much difficulty. However, the paper raises the need for professional training and feedback from students. One-third of the respondents express satisfaction with online teaching, despite low satisfaction about the effectiveness of online teaching of a design studio. The results convey the need for more engagement with digital tools and representational software on integrated platforms. The study finds consensus on the future potential of blended learning and advocates developing an integrated framework and curriculum for architecture education in India.
Originality/value
The paper synthesizes viewpoints on online teaching-learning of architecture program in wake of the pandemic from an educators' perspective. The emergent perspectives are viewed dialogically in context of global voices to articulate a future trajectory of blended learning in the domain of architecture education.
Environmental crisis and water contamination have led to worldwide exploration for advanced technologies for wastewater treatment, and one of them is photocatalytic degradation. A one-dimensional ...hollow nanofiber with enhanced photocatalytic properties is considered a promising material to be applied in the field. Therefore, we synthesized titanium dioxide hollow nanofibers (THNF) with extended surface area, light-harvesting properties and an anatase–rutile heterojunction via a template synthesis method and followed by a calcination process. The effect of calcination temperature on the formation and properties of THNF were determined and the possible mechanism of THNF formation was proposed. THNF nanofibers produced at 600 °C consisted of a mixture of 24.2% anatase and 75.8% rutile, with a specific surface area of 81.2776 m2/g. The hollow nanofibers also outperformed the other catalysts in terms of photocatalytic degradation of MB dye, at 85.5%. The optimum catalyst loading, dye concentration, pH, and H2O2 concentration were determined at 0.75 g/L, 10 ppm, pH 11, and 10 mM, respectively. The highest degradation of methylene blue dye achieved was 95.2% after 4 h of UV irradiation.
A 65-year-old male with a history of multiple myeloma and melanoma presented to the hospital with shortness of breath and lightheadedness. He was subsequently diagnosed with mild superior vena cava ...(SVC) syndrome due to a metastatic melanoma mediastinal mass. While melanoma frequently metastasizes to the lungs, the occurrence of SVC syndrome resulting from metastatic melanoma is exceedingly rare compared to other malignancies like lung cancer. Consequently, data on the incidence or prevalence of SVC syndrome caused by metastatic melanoma are sparse and variable. This case particularly underscores the rarity of melanoma causing SVC syndrome, as evidenced by the oncology team's request to perform a second biopsy to confirm the diagnosis. This case also highlights the need for a tailored diagnostic and management approach, providing valuable insights into the diverse presentations of melanoma and enriching the medical literature on this subject.
A 71-year-old male with a history of alcohol abuse and multiple suicide attempts was brought to the emergency department in an unconscious state. Initial assessment revealed profound obtundation and ...malnutrition. Laboratory findings demonstrated a significant anion gap metabolic acidosis with a high osmolar gap, suggestive of possible toxic alcohol ingestion. Despite negative serum alcohol levels, ethylene glycol poisoning was confirmed with a level of 226. Treatment included fluid resuscitation, bicarbonate therapy, and fomepizole administration. However, due to progressive multi-organ failure, continuous veno-venous hemodialysis was initiated. Despite interventions, the patient deteriorated rapidly, leading to a decision for hospice care, ultimately resulting in death. Ethylene glycol poisoning presents significant challenges in management, with potential complications including renal failure and multi-organ dysfunction. Fomepizole remains the cornerstone of treatment, but additional therapies such as ethanol administration were considered but ultimately deemed unnecessary due to associated risks. This case highlights the complexity and severity of ethylene glycol poisoning, emphasizing the need for early recognition and aggressive management strategies.
Introduction
Robotic-assisted laparoscopic prostatectomy (RALP) has largely replaced open radical prostatectomy in many centers. Radical perineal prostatectomy (RPP) is another less invasive approach ...that has not been widely adopted. RPP offers excellent exposure of the urinary sphincter and bladder neck that may provide good urinary function outcomes. We evaluate urinary function after RALP and RPP.
Methods
Retrospective review of a prospective radical prostatectomy database was performed. Urinary modules from the Expanded Prostate Cancer Index Composite—Urinary Function (EPIC-UF) questionnaire were used to determine urinary symptoms at baseline and at 6, 12, 18, and 24 months after surgery.
Results
753 men underwent RALP (
n
= 623) or RPP (
n
= 130). Of these, 558 had complete data and were included in our study (RALP:
n
= 458, RPP:
n
= 100). A higher number of patients undergoing RALP than RPP had pelvic lymph node dissection (20.2% vs. 0%,
p
< 0.0001) and cavernosal neurovascular bundle sparing (79.2% vs. 68.4%,
p
< 0.0001). 558 patients had complete EPIC-UF data. Overall urinary recovery was greater for RALP than RPP at 6 months (
p
= 0.028). Urinary incontinence and function were also more improved after RALP compared to RPP at 6 months (
p
= 0.021,
p
= 0.006). However, no differences in overall, urinary incontinence, or urinary function scores were seen at 12, 18, or 24 months. There was no difference between groups in urinary bother or irritative/obstructive symptoms at any time point.
Conclusions
RALP had more rapid recovery of urinary function at 6 months vs. RPP; at 12–24 months, however, RALP and RPP had similar urinary function recovery in all urinary subdomains.
Endoplasmic reticulum (ER) stress and oxidative stress promote endothelial dysfunction and atherosclerosis. Since vitamin D has been shown in several studies to lower the risk of cardiovascular ...disease, we examined the effects of vitamin D on ER stress and oxidative stress in endothelial cells. ER stress was measured using the placental secreted alkaline phosphatase assay and oxidative stress was measured by hydroethidine fluorescence. Expression of ER stress markers, including glucose-regulated protein 78, c-jun N-terminal kinase 1 phosphorylation, and eukaryotic initiation factor 2α phosphorylation, as well as X-box binding protein-1 splicing were measured in tunicamycin (TM)-treated human umbilical endothelial cells (HUVEC) treated with 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) and other vitamin D analogs. When TM and 1,25-(OH)2D3 were added simultaneously, 1,25-(OH)2D3 prevented ER stress. However, the effect was much stronger when cells were pre-treated with 1,25-(OH)2D3 for 24-h. However, ER stress was not inhibited by 25-OH vitamin D3 (25-OHD3) or the vitamin D analog EB1089. Both ZK191784 and the vitamin D metabolite 24,25-dihydroxyvitamin D3 were as effective as 1,25-(OH)2D3 in preventing ER stress. Similar effects were observed dextrose-induced stress. All of the compounds tested, except for 25-OHD3, inhibited dextrose-induced (27.5mM) oxidative stress and ER stress. Although TM with and without 1,25-(OH)2D3 had no effect on VDR expression, inhibition of VDR expression via siRNA prevented 1,25-(OH)2D3, ZK191784, EB1089, and 24,25-dihydroxyvitamin D3 from inhibiting dextrose-mediated SO generation. Furthermore, each vitamin D analog, with the exception of 25-OHD3, prevented dextrose-induced toxicity. These results suggest that vitamin D has a protective effect on vascular endothelial cells.
•Vitamin D and its metabolites/analogs inhibited ER stress in endothelial cells.•Similar effects were observed with hyperglycemia-induced ER stress and SO generation.•Vitamin D prevented high-dextrose cell death.•This suggests that vitamin D has a protective effect on endothelial cells.
Paraneoplastic syndromes are most frequently associated with lung cancer. This review considers a variety of paraneoplastic syndromes associated with lung cancer and discusses their pathophysiology, ...clinical features and management options.
Studies assessing the stone-free rate (SFR) after ureteroscopy are limited to expert centers with varied definitions of stone free. Real-world data including community practices related to surgeon ...characteristics and outcomes are lacking.
To evaluate the SFR for ureteroscopy and its predictors across diverse surgeons in Michigan.
We assessed the Michigan Urological Surgery Improvement Collaborative (MUSIC) clinical registry for patients with renal or ureteral stones treated with ureteroscopy between 2016 and 2021 who had postoperative imaging.
Stone free was defined as no fragments on imaging reports within 60 d entered by independent data abstractors. Factors associated with being stone free were examined using logistic regression, including annual surgeon volume. We then assessed variation in surgeon-level SFRs adjusted for risk factors.
We identified 6487 ureteroscopies from 164 surgeons who treated 2091 (32.2%) renal and 4396 (67.8%) ureteral stones. The overall SFRs were 49.6% (renal) and 72.7% (ureteral). Increasing stone size, lower pole, proximal ureteral location, and multiplicity were associated with not being stone free. Female gender, positive urine culture, use of ureteral access sheath, and postoperative stenting were associated with residual fragments when treating ureteral stones. Adjusted surgeon-level SFRs varied for renal (26.1-72.4%; p < 0.001) and ureteral stones (52.2-90.2%; p < 0.001). Surgeon volume was not a predictor of being stone free for renal stones. Limitations include the lack of imaging in all patients and use of different imaging modalities.
The real-world complete SFR after ureteroscopy is suboptimal with substantial surgeon-level variation. Interventions focused on surgical technique refinement are needed to improve outcomes for patients undergoing ureteroscopy and stone intervention.
Results from a diverse group of community practicing and academic center urologists show that for a large number of patients, it is not possible to be completely stone free after ureteroscopy. There is substantial variation in surgeon outcomes. Quality improvement efforts are needed to address this.
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