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With continued technological advancement and technical improvement of transcatheter aortic valve replacement (TAVR), it has become a desirable treatment option for aortic valve stenosis. Its minimally invasive approach compared to surgical aortic valve replacement offers the treatment to a broader patient population, mainly non-surgical candidates. A feared complication of TAVR is the occlusion of coronary artery ostium by the native aortic valve leaflet due to its displacement by the expanded transcatheter valve. Bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction (BASILICA) is a technique developed to mitigate this risk by creating a lengthwise laceration of the left and/or right aortic valve leaflets prior to TAVR. Patient outcomes following TAVR with BASILICA have been promising. Meticulous preoperative examination, patient selection, and hemodynamic management are imperative. With continued refinement, BASILICA may further expand the application of TAVR to patients at high risk for coronary occlusion associated with the procedure.

ObjectiveThe hypotension prediction index (HPI) is a novel parameter developed by Edwards Lifesciences (Irvine, CA) that is obtained through an algorithm based on arterial pressure waveform characteristics. Past studies have demonstrated its accuracy in predicting hypotensive events in noncardiac surgeries. The authors aimed to evaluate the use of the HPI in cardiac surgeries requiring cardiopulmonary bypass (CPB).DesignProspective cohort feasibility study.SettingSingle university medical center.ParticipantsSequential adult patients undergoing elective cardiac surgeries requiring CPB between October 1, 2018, and December 31, 2018.InterventionsHPI monitor was connected to the patient's arterial pressure transducer. Anesthesiologists and surgeons were blinded to the monitor output.Measurements and main resultsHPI values and hypotensive events were recorded before and after CPB. The primary outcomes were the area under the curve (AUC) of the receiver operating characteristic curve, sensitivity, and specificity of HPI predicting hypotension. The AUC, sensitivity, and specificity for HPI lead time to hypotension five minutes before the event were 0.90 (95% confidence interval [CI]: 0.853-0.949), 84% (95% CI: 77.7-90.5), and 84% (95% CI: 70.9-96.8), respectively. Ten minutes before the event AUC, sensitivity, and specificity for HPI lead time to hypotension were 0.83 (95% CI: 0.750-0.905), 79% (95% CI: 69.8-88.1), and 74% (95% CI: 58.8-89.6), respectively. Fifteen minutes before the hypotensive event AUC, sensitivity, and specificity for HPI lead time to hypotension were 0.83 (95% CI: 0.746-0.911), 79% (95% CI: 68.4-89.0), and 74% (95% CI: 58.8-89.6), respectively.ConclusionHPI predicted hypotensive episodes during cardiac surgeries with a high degree of sensitivity and specificity.

The COVID‐19 pandemic led to a major disruption to health services across the world. The aim of this population‐based study was to assess the downstream effects of the pandemic on diagnostic tests and treatment activities related to prostate cancer (PC). The Australian Government Department of Health Medicare Benefits Schedule and the Pharmaceutical Benefits Scheme databases were queried from January 2010 to June 2022. Two interrupted time series were performed Pre‐COVID (January 2010 to February 2020) and peri‐COVID (March 2020 to June 2022). Temporal modeling was performed to account for seasonal variation. Pre‐COVID‐19, monthly prostate‐specific antigen (PSA) testing showed a declining trend and testing decreased by 81 tests per 100 000 annually. A single‐month 38% drop in PSA testing was observed in April 2020; this corresponded to Australia's first wave. No change was observed in the rate of prostate biopsies. Peri‐COVID‐19 outbreaks, there was a slight shift toward the use of long‐acting androgen deprivation therapy (ADT) at 4% with a predilection still for short‐acting agents. with no registered change in the overall volume of radiotherapy or surgery. There were no deficits in the number of diagnostic and treatment activities for men with PC. Aside from a slight shift toward long‐acting ADT use during the pandemic, no other patterns were observed. The longer‐term impact such as missed diagnosis or late presentation affecting chances of survival due to COVID‐19 is yet to be ascertained. [ABSTRACT FROM AUTHOR]

PurposeHereditary nonpolyposis colon cancer is caused by mutations in DNA mismatch repair genes, predominantly MLH1 and MSH2. Classic MLH1 mutations cause an approximately 20-fold increase in colorectal cancer susceptibility. Recently, we identified a hypomorphic allele, MLH1 D132H , which impairs, but does not completely eliminate the function of MLH1 in tumor suppression. MLH1 D132H confers an approximately fivefold increase in colorectal cancer susceptibility and was first described in a cohort of Israeli colorectal cancer patients, with an estimated allele frequency of 1.3 percent. Because MLH1 D132H has only recently been described, the ethnic distribution of this risk allele is not well understood. This study was undertaken to determine both the frequencies of this risk allele in ethnic groups outside of Israel and whether families harboring this mutation have susceptibility to extracolonic cancers in the hereditary nonpolyposis colon cancer spectrum.MethodsWe genotyped two independent cohorts: 629 population-based colorectal cancer patients ascertained from clinics in Orange, Imperial, and San Diego Counties, and 515 endometrial cancer patients ascertained from gynecologic oncology clinics in the Midwestern United States.ResultsMLH1 D132H was not detected in either study cohort, which together totaled more than 1,100 American colorectal cancer and endometrial cancer patients.ConclusionsThe MLH1 D132H risk variant has significantly lower allele frequency in American compared with Israeli cancer patients and, alone, is unlikely to explain significant amounts of American sporadic colorectal cancer or uterine cancer susceptibility. Genetic testing for the MLH1 D132H allele exclusively is therefore unlikely to be cost effective for genetic risk assessment in American population-based and clinic-based colorectal cancer and endometrial cancer patients.

Purpose: Prostate cancer (PC) is more common in the older population and the use of hormonal therapy in PC can increase medical frailty and cognitive decline. This narrative review examines the impact of androgen deprivation therapies (ADTs) and next-generational hormonal therapies (NGHT) on cognitive function outcomes amongst patients with hormone-sensitive or castrate-resistant PC. Materials and Methods: Six electronic databases were searched from January 2000 to June 2022 for quantitative studies to evaluate the impacts of hormonal therapies (ADT, combined androgen blockade, and NGHT) on cognitive functions in men with PC. Results: Of the 36 studies identified, 20 studies reported no effect of hormonal therapies on any cognitive domain while 16 studies found possible declines in at least one domain. The domains assessed were highly variable and objective assessment measurements were not standardized or widely adopted. While the results have been inconsistent, a relationship between declining androgen levels and poorer performances in the visuospatial and visual memory domains has been highlighted. It was not possible to distinguish the degree of cognitive parameter changes between the populations of hormone-sensitive and castrate-resistant PC. Conclusions: While the exact impact of ADT and NGHT on cognitive function in men with PC remains controversial, appropriate care should be undertaken especially in older and frail individuals, specifically in those with progressive or established visuospatial or visual memory deficits. [ABSTRACT FROM AUTHOR]

The forkhead box (Fox) fl transcription factor is expressed in the mouse splanchnic (visceral) mesoderm, which contributes to development of the liver, gallbladder, lung, and intestinal tract. Pulmonary hemorrhage and peripheral microvascular defects were found in approximately half of the newborn Foxfl(+/-) mice, which expressed low levels of lung Foxfl mRNA [low-Foxfl(+/-) mice]. Microvascular development was normal in the surviving newborn high-Foxfl(+/-) mice, which compensated for pulmonary Foxfl haploinsufficiency and expressed wild-type Foxfl levels. To identify expression of genes regulated by Foxfl, we used Affymetrix microarrays to determine embryonic lung RNAs influenced by Foxfl haploinsufficiency. Embryonic Foxfl(+/-) lungs exhibited diminished expression of hepatocyte growth factor receptor c-Met, myosin VI, the transcription factors SP-3, BMI-1, ATF-2, and glucocorticoid receptor, and cell cycle inhibitors p53, [p21.sup.Cip1], retinoblastoma, and p107. Furthermore, Notch-2 signaling was decreased in embryonic Foxfl (+/-) lungs, as evidenced by significantly reduced levels of the Notch-2 receptor and the Notch-2 downstream target hairy enhancer of split-1. The severity of the Notch-2-signaling defect in 18-day postcoitus Foxfl(+/-) lungs correlated with Foxfl mRNA levels. Disruption of pulmonary Notch-2 signaling continued in newborn low-Foxfl(+/-) mice, which died of lung hemorrhage and failed to compensate for Foxfl haploinsufficiency. In contrast, in newborn high-Foxfl(+/-) lungs, Notch-2 signaling was restored to the level found in wild-type mice, which was associated with normal microvascular formation and survival. Foxfl haploinsufficiency disrupted pulmonary expression of genes in the Notch-2-signaling pathway and resulted in abnormal development of lung microvasculature. winged helix DNA-binding domain; Notch-2 receptor; microarray analysis; forkhead box transcription factor; hepatocyte nuclear factor/ forkhead homolog-8; forkhead-related activator-1

Scrotal-inguino-retroperitoneal (SIR) lymphocele is a rare complication following kidney transplant. This entity is characterized by a tract originating in the retroperitoneal space, through the inguinal canal and scrotum following lymph hydrodissection. Systematic review investigating SIR lymphocele yielded cases with open fenestration of the sac into the peritoneum as treatment. We described a case report of a male in his 60s with a functioning kidney transplant and SIR lymphocele, which was successfully managed in the short term with percutaneous drainage of the collection. However, the collection recurred and computed tomography scan showed a multiloculated collection that prompted surgical management. Intraoperatively, the encapsulated fluid-filled tract was excised and a drain was placed, which was removed 48 h later. The patient wore a hernia belt for 6 weeks as support. He had no recurrence of his lymphocele following serial reviews for 9 months now. [ABSTRACT FROM AUTHOR]

This paper presents development of an innovative tool for online power system operation. It is designed to operate in an Energy Control Center (ECC) environment. Online application consists of using the developed Optimal Power Flow (OPF) based Loss Minimization (LM) function for real time power system corrective actions by ECC dispatchers. The results of online power system operations using the LM function are reported to demonstrate economic and security gains for power system operations. Keywords: Optimal Power Flow, Loss Minimization, Suboptimal, Energy Management System (EMS), Energy Control Center.

This article discusses the prevalence and management of penile cancer, a rare genitourinary cancer that is predicted to become more common in the future. The study analyzed data from the SEER database and found that while most patients presented with lower-stage cancer, the overall survival rate decreased as the cancer advanced. The article highlights the need for further research to optimize treatment strategies and improve cancer care, as well as the importance of raising awareness and implementing preventive measures. The authors suggest centralizing penile cancer cases in expert centers to improve clinical care and advocate for international research collaboration to address the disparities in cancer epidemiology and mortality rates. [Extracted from the article]

The leading cause of cancer-related deaths-hepatocellular carcinoma (HCC) in relation with Forkhead Box m1b (Foxm1b) transcription factor is studied. The experiments reveal that Foxm1b transcription factor is required for proliferative expansion and constitutes a potential target for human HCC tumor therapy to reduce spread of liver cancer.

The Forkhead Box (Fox) family of transcription factors plays important roles in regulating expression of genes involved in cellular proliferation and differentiation. In a previous study, we showed that newborn foxf1(+/-) mice with diminished Foxf1 levels exhibited abnormal formation of pulmonary alveoli and capillaries and died postnatally. Interestingly, surviving newborn foxf1(+/-) mice exhibited increased pulmonary Foxf1 levels and normal adult lung morphology, suggesting that wild-type Foxf1 levels are required for lung development and function. The present study was conducted to determine whether adult foxf1(+/-) mice were able to undergo lung repair similar to that observed in wild-type mice. We demonstrated that adult foxf1(+/-) mice died from severe lung hemorrhage after butylated hydroxytoluene (BHT) lung injury and that this phenotype was associated with a 10-fold decrease in pulmonary Foxf1 expression and increased alveolar endothelial cell apoptosis that disrupted capillary integrity. Furthermore, BHT-induced lung hemorrhage of adult foxf1(+/-) mice was associated with a drastic reduction in expression of the Flk-1, bone morphogenetic protein-4, surfactant protein B, platelet endothelial cell adhesion molecule, and vascular endothelial cadherin genes, whereas the expression of these genes was either transiently diminished or increased in wild-type lungs after BHT injury. Because these proteins are critical for lung morphogenesis and endothelial homeostasis, their decreased mRNA levels are likely contributing to BHT-induced lung hemorrhage in foxf1(+/-) mice. Collectively, our data suggest that sustained expression of Foxf1 is essential for normal lung repair and endothelial cell survival in response to pulmonary cell injury. winged helix deoxyribonucleic acid-binding domain; Flk-1; bone morphogenetic protein-4; surfactant protein B; platelet endothelial cell adhesion molecule-1; vascular endothelial cadherin; butylated hydroxytoluene lung injury; endothelial cells

Kalinichenko, Vladimir V., Lorena Lim, Brian Shin, and Robert H. Costa. Differential expression of forkhead box transcription factors following butylated hydroxytoluene lung injury. Am J Physiol Lung Cell Mol Physiol 280: L695-L704, 2001.--The forkhead box (Fox) proteins are a growing family of transcription factors that have important roles in cellular proliferation and differentiation and in organ morphogenesis. The Fox family members hepatocyte nuclear factor (HNF)-3[Beta] (Foxa2) and HNF-3/forkhead homolog (HFH)-8 (FREAC-1, Foxf1) are expressed in adult pulmonary epithelial and mesenchymal cells, respectively, but these cells display only low expression levels of the proliferation-specific HFH-11B gene (Trident, Foxm1b). The regulation of these Fox transcription factors in response to acute lung injury, however, has yet to be determined. We report here on the use of butylated hydroxytoluene (BHT)-mediated lung injury to demonstrate that HFH-11 protein and RNA levels were markedly increased throughout the period of lung repair. The maximum levels of HFH-11 were observed by day 2 following BHT injury when both bronchiolar and alveolar epithelial cells were undergoing extensive proliferation. Although BHT lung injury did not alter epithelial cell expression of HNF-3[Beta], a 65% reduction in HFH-8 mRNA levels was observed during the period of mesenchymal cell proliferation. HFH-8-expressing cells were colocalized with platelet endothelial cell adhesion molecule-1-positive alveolar endothelial cells and with [Alpha]-smooth muscle actin-positive peribronchiolar smooth muscle cells. winged helix/forkhead box DNA binding domain; hepatocyte nuclear factor 3/forkhead homolog; alveolar endothelial cell; alveolar type II cell; bronchiolar epithelial cells.

Therapeutic approaches that enhance thrombolysis by combining recombinant tissue plasminogen activator (rtPA), ultrasound, and/or microbubbles (MBs) are known as sonothrombolysis techniques. To date, sonothrombolysis approaches have primarily utilized commercially available MB formulations (or derivatives thereof) with diameters in the range 1-4 µm and circulation lifetimes between 5 and 15 min. The present study evaluated the in vitro sonothrombolysis efficacy of large diameter MBs ( d ≥ 10 µm) with much shorter lifetimes that were produced on demand and in close proximity to the blood clot using a flow-focusing microfluidic device. MBs with a N gas core and a non-crosslinked bovine serum albumin shell were produced with diameters between 10 and 20 µm at rates between 50 and 950 × 10 per second. Use of these large MBs resulted in approximately 4.0-8.8 fold increases in thrombolysis rates compared to a clinical rtPA dose and approximately 2.1-4.2 fold increases in thrombolysis rates compared to sonothrombolysis techniques using conventional MBs. The results of this study indicate that the large diameter microbubbles with transient stability are capable of significantly enhanced in vitro sonothrombolysis rates when delivered directly to the clot immediately following production by a flow focusing microfluidic device placed essentially in situ adjacent to the clot. [ABSTRACT FROM AUTHOR]