Targeting the retinoic acid signaling pathway as a modern precision therapy against cancers

Retinoic acid (RA) is a vital metabolite derived from vitamin A. RA plays a prominent role during development, which helps in embryological advancement and cellular differentiation. Mechanistically, RA binds to its definite nuclear receptors including the retinoic acid receptor and retinoid X receptor, thus triggering gene transcription and further consequences in gene regulation. This functional heterodimer activation later results in gene activation/inactivation. Several reports have been published related to the detailed embryonic and developmental role of retinoic acids and as an anti-cancer drug for specific cancers, including acute promyelocytic leukemia, breast cancer, and prostate cancer. Nonetheless, the other side of all-trans retinoic acid (ATRA) has not been explored widely yet. In this review, we focused on the role of the RA pathway and its downstream gene activation in relation to cancer progression. Furthermore, we explored the ways of targeting the retinoic acid pathway by focusing on the dual role of aldehyde dehydrogenase (ALDH) family enzymes. Combination strategies by combining RA targets with ALDH-specific targets make the tumor cells sensitive to the treatment and improve the progression-free survival of the patients. In addition to the genomic effects of ATRA, we also highlighted the role of ATRA in non-canonical mechanisms as an immune checkpoint inhibitor, thus targeting the immune oncological perspective of cancer treatments in the current era. The role of ATRA in activating independent mechanisms is also explained in this review. This review also highlights the current clinical trials of ATRA in combination with other chemotherapeutic drugs and explains the future directional insights related to ATRA usage

Low fingertip temperature rebound measured by digital thermal monitoring strongly correlates with the presence and extent of coronary artery disease diagnosed by 64-slice multi-detector computed tomography

Previous studies showed strong correlations between low fingertip temperature rebound measured by digital thermal monitoring (DTM) during a 5 min arm-cuff induced reactive hyperemia and both the Framingham Risk Score (FRS), and coronary artery calcification (CAC) in asymptomatic populations. This study evaluates the correlation between DTM and coronary artery disease (CAD) measured by CT angiography (CTA) in symptomatic patients. It also investigates the correlation between CTA and a new index of neurovascular reactivity measured by DTM. 129 patients, age 63 ± 9 years, 68% male, underwent DTM, CAC and CTA. Adjusted DTM indices in the occluded arm were calculated: temperature rebound: aTR and area under the temperature curve aTMP-AUC. DTM neurovascular reactivity (NVR) index was measured based on increased fingertip temperature in the non-occluded arm. Obstructive CAD was defined as ≥50% luminal stenosis, and normal as no stenosis and CAC = 0. Baseline fingertip temperature was not different across the groups. However, all DTM indices of vascular and neurovascular reactivity significantly decreased from normal to non-obstructive to obstructive CAD [(aTR 1.77 ± 1.18 to 1.24 ± 1.14 to 0.94 ± 0.92) (P = 0.009), (aTMP-AUC: 355.6 ± 242.4 to 277.4 ± 182.4 to 184.4 ± 171.2) (P = 0.001), (NVR: 161.5 ± 147.4 to 77.6 ± 88.2 to 48.8 ± 63.8) (P = 0.015)]. After adjusting for risk factors, the odds ratio for obstructive CAD compared to normal in the lowest versus two upper tertiles of FRS, aTR, aTMP-AUC, and NVR were 2.41 (1.02–5.93), P = 0.05, 8.67 (2.6–9.4), P = 0.001, 11.62 (5.1–28.7), P = 0.001, and 3.58 (1.09–11.69), P = 0.01, respectively. DTM indices and FRS combined resulted in a ROC curve area of 0.88 for the prediction of obstructive CAD. In patients suspected of CAD, low fingertip temperature rebound measured by DTM significantly predicted CTA-diagnosed obstructive disease

A Study of Focal and Segmental Glomerulosclerosis according to the Columbia Classification and Its Correlation with the Clinical Outcome

Introduction Focal and segmental glomerulosclerosis (FSGS) is a leading cause of nephrotic syndrome in both adults and children. The “Columbia classification of FSGS” includes five variants; not otherwise specified (NOS), tip, perihilar, cellular, and collapsing variants that may have different prognostic and therapeutic implications. Materials and Methods This is a retrospective study and was carried out in the Department of Histopathology, Apollo Hospitals, Hyderabad. Of a total of 11,691 kidney biopsies over a 7-year period, from 2006 to 2012, 824 cases were diagnosed as FSGS, of which 610 cases in which detailed clinical findings were available were included in this study. FSGS was then categorized according to the Columbia classification. Results FSGS, NOS was the predominant histomorphological variant. Serum creatinine was significantly high in the collapsing variant, followed by NOS. Follow-up data was available for 103 cases,72.8% had complete remission, 10.6% had partial remission, and in 16.5 % there was no remission. Relapses were observed in 6.7% cases, two patients (1.9%) succumbed, and 4.8% cases progressed to chronic kidney disease. Conclusion This study showed that perihilar variant was less prevalent, with tip and cellular variants being more prevalent in Indian subcontinent compared to Western literature. Collapsing variant was also less common

Two unusual cases of microvascular thrombosis in the immediate posttransplant period

We present two unusual cases of microvascular thrombosis in the immediate posttransplant period resulting in graft loss. The first was a 20-year-old female with a cadaveric renal transplant with immediate graft dysfunction due to microthrombi of probable donor origin, with nonrecovery of renal function nine months’ posttransplant. The second was a 23-year-old male with unrelated live kidney transplant with hyperacute rejection due to anti-endothelial antibodies

Vascular dysfunction measured by fingertip thermal monitoring is associated with the extent of myocardial perfusion defect

Previous studies have shown that vascular dysfunction measured by digital thermal monitoring (DTM) during an arm-cuff reactive hyperemia procedure correlates with the severity of coronary artery disease measured by coronary artery calcium in asymptomatic patients. Current study investigates the correlation between DTM and abnormal myocardial perfusion imaging (MPI). About 116 consecutive patients with chest discomfort, age 57 ± 10 years, underwent MPI, DTM and Framingham Risk Score (FRS) assessment. Fingertip temperature rebound (TR), DTM index of vascular reactivity, was assessed after a 2-minute arm-cuff reactive hyperemia test. The extent of myocardial perfusion defect was measured by summed stress score (SSS). TR decreased from SSS < 4 (1.61 ± 0.15) to 4 ≤ SSS ≤ 8 (0.5 ± 0.22) to 9 ≤ SSS ≤ 13 (0.26 ± 0.15) to SSS > 13 (−0.37 ± 0.19) (P = .0001). After adjusting for cardiac risk factors, the odds ratio of the lowest versus two upper tertiles of TR was 3.93 for SSS ≥ 4 and 9.65 for SSS ≥ 8 compared to SSS < 4. TR correlated well with SSS (r = −0.88, P = .0001). Addition of TR to FRS increased the area under the ROC curve to predict abnormal MPI, SSS ≥ 4, from 0.65 to 0.84 (P < .05). Vascular dysfunction measured by DTM is associated with the extent of myocardial perfusion defect independent of age, gender, and cardiac risk factors

Electronic Visualisation in the Arts EVA

This paper outlines an investigation and describes strategies to capture, simulate and reproduce experiences originally designed for large scale immersive architectures within Virtual Reality. Applications and experiences created for a specific immersive platform depend on the complex and costly technical infrastructure they were originally designed for. Descriptions and video documentation only go so far in illustrating an immersive experience. The embodied aspect, the emotional engagement and the dimensional extend, central to immersion, is mostly lost in translation. This project offers a prototypical implementation of a large scale virtual exhibition, incorporating various immersive architectures and applications situated within a fictional 3D scene. The motivation behind this project is to provide a framework to showcase and for the conservation of immersive experiences and systems outside specialised facilities and labs. Furthermore, it presents a test-bed and space for experimentation to design and evaluate immersive experiences and architecture before they are developed at full scale