Saroglitazar Enhances Memory Functions and Adult Neurogenesis via Up-Regulation of Wnt/ß Catenin Signaling in the Rat Model of Dementia.

Peroxisome proliferator-activated receptors (PPARs) have emerged as a promising target for the treatment of various neurodegenerative disorders. Studies have shown that both PPAR α & γ individually modulate various pathophysiological events like neuroinflammation and insulin resistance, which are known to variedly affect neurogenesis. Our study aimed to evaluate the effect of saroglitazar (SGZR), a dual PPAR agonist, on adult neurogenesis and spatial learning and memory, in intracerebroventricular streptozotocin (ICV STZ)-induced dementia in rats. We have found that SGZR at the dose of 4 mg/kg per oral showed significant improvement in learning and memory compared to ICV STZ-treated rats. A substantial increase in neurogenesis was observed in the subventricular zone (SVZ) and the dentate gyrus (DG), as indicated by an increase in the number of 5-bromo-2'-deoxyuridine (BrdU)+ cells, BrdU+ nestin+ cells, and doublecortin (DCX)+cells. Treatment with SGZR also decreased the active form of glycogen synthase kinase 3ß (GSK3ß) and hence enhanced the nuclear translocation of the ß-catenin. Enhanced expression of Wnt transcription factors and target genes indicates that the up-regulation of Wnt signaling might be involved in the observed increase in neurogenesis. Hence, it can be concluded that the SGZR enhances memory functions and adult neurogenesis via the upregulation of Wnt ß-catenin signaling in ICV STZ-treated rats.

Molecular recognition and proteoglycan mimic arrangement: modulating cisplatin toxicity.

We have demonstrated that cisplatin (CP), an anticancer drug, showed a preference for binding the sulfated-L-iduronic acid (S-L-IdoA) unit over the sulfated-D-glucuronic acid unit of heparan sulfate. The multivalency of S-L-IdoA, such as in the proteoglycan mimic, resulted in distinct modes of cell-surface engineering in normal and cancer cells, with these disparities having a significant impact on CP-mediated toxicity.

Relationship between difference of preoperative and cardiopulmonary bypass mean arterial pressure, and acute kidney injury in cardiac surgical patients undergoing valve surgery.

BACKGROUND: Modifiable and non-modifiable factors contribute to development and progression of acute kidney injury (AKI) during cardiac surgery. We hypothesized that, the difference between preoperative mean arterial pressure (MAP) and the average mean arterial pressure maintained on cardiopulmonary bypass (CPB) would be strongly predictive of AKI. We also measured plasma Neutrophil gelatinase-associated lipocalin (NGAL), to establish its association with cardiac surgery associated-AKI (CSA-AKI). METHODS: One hundred and twelve high-risk patients undergoing valve, and valve plus coronary artery bypass grafting (CABG) surgery under cardiopulmonary bypass (CPB) were included in this study. Delta mean arterial pressure (MAP) was calculated as the difference between the average of pre-operative and on-bypass MAP, and blood was sampled for NGAL levels, at baseline, and 6-h after CPB. Detailed data collection was done, tabulating most of the factors which might influence development of post-operative cardiac surgery associated-AKI (CSA-AKI). To define CSA-AKI within the first 24-h post-operatively, the Kidney Disease Improving Global Outcomes (KDIGO) classification was used. RESULTS: Out of 112 patients, 44 (39.3%) developed CSA-AKI postoperatively. With an ROC analysis cut-off of delta MAP of more than 25.67 mmHg, 46.4% patients developed post-operative AKI, and the average CPB flows which were 1.8 ± 0.2 were not contributory to the development of early CSA-AKI. In our study, ELISA test for human NGAL was performed on serum samples, and the estimated cut-off value of 1661 ng/mL was found to be significantly associated with early CSA-AKI. CONCLUSIONS: Delta MAP and CPB flows are not related to early post-surgical CSA-AKI in cases with prior high-risk elements. However, baseline serum NGAL, as well as its percent change during the early post-surgical period independently predicted the development of CSA-AKI. This implies that, there may be patients with a higher pre-operative preponderance to develop this complication, which could actually be delineated by the use of serum NGAL estimations at baseline.

Comparison of preformed microcuff and preformed uncuffed endotracheal tubes in pediatric cleft palate surgery-A randomized controlled trial.

BACKGROUND AND AIMS: Airway management in children with oral cleft surgery carries unique challenges, concerning the proximity of the surgical site and the tracheal tube. We hypothesized that using a Microcuff oral RAE tube would reduce tube exchange and migration rate. We aimed to compare the performance of Microsoft and uncuffed oral performed tracheal tubes in children undergoing cleft palate surgeries regarding the rate of tracheal tube exchange, endobronchial intubation, and ventilatory parameters. METHODS: One hundred children scheduled for cleft palate surgery were randomized into two groups. In the uncuffed group (n = 50), the tracheal tube was selected using the Modified Coles formula, and in the Microcuff (n = 50) group, the manufacturer's recommendations were followed. Intraoperatively, we compared the primary outcome of tube exchange using the chi-square test. The leak pressure and ventilatory parameters after head extension and mouth gag application were measured in both groups. RESULTS: The tracheal tube exchange rate was significantly lower in the Microcuff group (0/50) than in uncuffed (19/50) preformed tubes (0 vs. 38% respectively; p <.001). The uncuffed and Microcuff tracheal tube were comparable concerning ventilation parameters and leak pressure of finally placed tubes (17.78 ± 3.95 vs. 19.26 ± 3.81 cm H2 O respectively, with a mean difference (95% CI) of -1.48 (-0.01-2.98); p-value =0.059. Cuff pressure did not vary significantly during the initial hour, and the incidence of postoperative airway morbidity between uncuffed and Microcuff tube was comparable, 5/50 (10%) versus 7/50 (14%) with risk ratio (95% CI) of 0.71(0.24-2.1), p value .49. CONCLUSION: Microcuff oral preformed tubes performed better than uncuffed tubes regarding tube exchange during cleft palate surgery.

Transmembrane pH gradient imaging in rodent glioma models.

A unique feature of the tumor microenvironment is extracellular acidosis in relation to intracellular milieu. Metabolic reprogramming in tumors results in overproduction of H+ ions (and lactate), which are extruded from the cells to support tumor survival and progression. As a result, the transmembrane pH gradient (ΔpH), representing the difference between intracellular pH (pHi) and extracellular pH (pHe), is posited to be larger in tumors compared with normal tissue. Controlling the transmembrane pH difference has promise as a potential therapeutic target in cancer as it plays an important role in regulating drug delivery into cells. The current study shows successful development of an MRI/MRSI-based technique that provides ΔpH imaging at submillimeter resolution. We applied this technique to image ΔpH in rat brains with RG2 and U87 gliomas, as well as in mouse brains with GL261 gliomas. pHi was measured with Amine and Amide Concentration-Independent Detection (AACID), while pHe was measured with Biosensor Imaging of Redundant Deviation in Shifts (BIRDS). The results indicate that pHi was slightly higher in tumors (7.40-7.43 in rats, 7.39-7.47 in mice) compared with normal brain (7.30-7.38 in rats, 7.32-7.36 in mice), while pHe was significantly lower in tumors (6.62-6.76 in rats, 6.74-6.84 in mice) compared with normal tissue (7.17-7.22 in rats, 7.20-7.21 in mice). As a result, ΔpH was higher in tumors (0.64-0.81 in rats, 0.62-0.65 in mice) compared with normal brain (0.13-0.16 in rats, 0.13-0.16 in mice). This work establishes an MRI/MRSI-based platform for ΔpH imaging at submillimeter resolution in gliomas.

Thoracic organ transplantation and pregnancy outcomes: systematic review and meta-analysis.

PURPOSE: Pre-conceptual comorbidities, an inherent risk of graft loss, rejection during pregnancy, and the postpartum period in women with thoracic lung transplant may predispose them to increased risk of adverse feto-maternal outcomes. The study aimed to systematically analyze and assess the risk of adverse pregnancy outcomes in women with thoracic organ transplant. METHODS: MEDLINE, EMBASE, and Cochrane library were searched for publication between January 1990 and June 2020. Risk of bias was assessed using Joanna Briggs critical appraisal tool for case series. The primary outcomes included maternal mortality and pregnancy loss. The secondary outcomes were maternal complications, neonatal complications, and adverse birth outcomes. The analysis was performed using the DerSimonian-Laird random effects model. RESULTS: Eleven studies captured data from 275 parturient with thoracic organ transplant describing 400 pregnancies. The primary outcomes included maternal mortality {pooled incidence (95% confidence interval) 4.2 (2.5-7.1) at 1 year and 19.5 (15.3-24.5) during follow-up}. Pooled estimates yielded 10.1% (5.6-17.5) and 21.8% (10.9-38.8) risk of rejection and graft dysfunction during and after pregnancy, respectively. Although 67% (60.2-73.2) of pregnancies resulted in live birth, total pregnancy loss and neonatal death occurred in 33.5% (26.7-40.9) and 2.8% (1.4-5.6), respectively. Prematurity and low birth weight were reported in 45.1% (38.5-51.9) and 42.7% (32.8-53.2), respectively. CONCLUSIONS: Despite pregnancies resulting in nearly 2/3rd of live births, high incidence of pregnancy loss, prematurity and low birth weight remain a cause of concern. Focused pre-conceptual counseling to avoid unplanned pregnancy, especially in women with transplant-related organ dysfunctions and complications, is vital to improve pregnancy outcomes. PROSPERO NUMBER: CRD42020164020.

Fishery, growth, mortality, and stock assessment of endangered Tor putitora from Tehri dam reservoir, Uttarakhand, Himalayan foothills of India in relation to environmental variables.

The current study determined Tor putitora (Hamilton, 1822) fishery, growth, mortality, and population characteristics using length-frequency data assembled monthly from the Tehri dam reservoir in Uttarakhand from January to December 2022. The estimation data was separated into 40-mm class intervals, and population parameters were investigated and computed using the FiSAT-II software tool. W = 0.0101 L2.996, where a = 0.0101 and b = 2.99, were determined as the length-weight relationships, and the growth performance index (ϕ) was computed to be 5.40. Tor putitora commercial catches in the Tehri dam reservoir were dominated by length groups of 360-399 and 320-359 mm. Different growth parameters were estimated using length-frequency data as L∞ = 987.00 mm, K = 0.26 yr-1, and t0 = -0.0003 years. Z, M, and F mortality coefficients were estimated to be 1.01, 0.27, and 0.73, respectively. At the end of the first, second, third, fourth, fifth, sixth, and seventh years, the fish measured 226, 400, 535, 638, 718, and 780, and 827, respectively. The estimated value of the exploitation rate (E) was 0.73 using the length-converted catch curve approach, which was determined to be somewhat higher than the optimum value (0.50). Tor putitora recruitment patterns from the Tehri dam reservoir reveal that the species only has one recruitment pattern every year, and that solely occurs from June to September. The current exploitation level (0.73) has already exceeded the maximum fishing pressure (Emax = 0.508), indicating that there is a decline in the catch at the current fishing pressure, and a further increase in fishing efforts may lead to a decline in the stock, which may be detrimental to the sustainable fishery of Tor putitora in the Tehri dam reservoir, Uttarakhand, India.

Pure shift edited NMR methodologies for the extraction of Homo- and heteronuclear couplings with ultra-high resolution.

The scalar couplings that result in the splitting of the signals in the NMR spectrum arise due to the interaction of the nuclear spins, whereby the spin polarization is transmitted through chemical bonds. The interaction strengths depend inter alia on the number of consecutive chemical bonds intervening between the two interacting spins and on the molecular conformation. The pairwise interaction of many spins in a molecule resulting in a complex spectrum poses a severe challenge to analyse the spectrum and hence the determination of magnitudes and signs of homo- and heteronuclear couplings. The problem is more severe in the analysis of 1H spectra than the spectra of most of the other nuclei due to the often very small chemical shift dispersion. As a consequence, the straightforward analysis and the accurate extraction of the coupling constants from the 1H spectrum of a complex spin system continues to remain a challenge, and often may be a formidable task. Over the years, the several pure shift-based one-dimensional and two-dimensional methodologies have been developed by workers in the field, which provide broadband homonuclear decoupling of proton spectra, removing the complexity but at the cost of the very informative scalar couplings. To circumvent this problem, several one-dimensional and two-dimensional NMR experiments have been developed for the determination of homonuclear and heteronuclear couplings (nJHX, where n = 1,2,3) while retaining the high resolution obtained by implementing pure shift strategies. This review attempts to summarize the extensive work reported by a large number of researchers over the years for the accurate determination of homo- and heteronuclear scalar couplings.

Ultrasound-Guided Radial Arterial Catheterization in Patients With Regurgitant and Stenotic Left-Sided Cardiac Valvular Lesions.

Background. The pulse characteristics of arterial circulation might affect radial artery catheterization's success rate. Therefore, we hypothesized that the success rate of radial artery catheterization would be lower in the left-sided severe stenotic valvular lesion group than severe regurgitant valvular lesion group. Methods. This prospective study was conducted among patients with left-sided cardiac valvular lesions undergoing cardiac and non-cardiac surgery. The patients with left-sided severe valvular stenosis and left-sided severe valvular regurgitation were included in the study. Radial artery cannulation was performed using an ultrasound-guided out-of-plane short-axis approach. The outcome measures were success rate, number of attempts, and cannulation time. Result. One hundred fifty-two patients were recruited for the study, and all were eligible for final analysis. The first attempt success rate was non-significantly higher in the stenotic valvular lesion group than the regurgitant group (69.7% vs 56.6%; P = .09). Furthermore, the number of attempts (median; 95% CI) was significantly higher in the regurgitant group (1; 1.2-1.43 vs 1; 1.38-1.67; P = .04). However, it may not be of clinical relevance. Moreover, the cannulation time and the number of redirections of the cannula were comparable. Heart rate was significantly higher in the regurgitant group (91.8 ± 13.9 vs 82.26 ± 15.92 beats/min; P = .00), while the incidence of atrial fibrillation was significantly higher in the stenotic lesion (P = .00). No failure was reported, and the incidence of periarterial hematoma was comparable. Conclusion. The success rate of ultrasound-guided radial arterial catheterization is comparable in left-sided stenotic valvular and regurgitant lesion groups.