Effect of Incomplete Cryoablation and Matrix Metalloproteinase Inhibition on Intratumoral CD8+ T-Cell Infiltration in Murine Hepatocellular Carcinoma.

Background Image-guided tumor ablation is the first-line therapy for early-stage hepatocellular carcinoma (HCC), with ongoing investigations into its combination with immunotherapies. Matrix metalloproteinase (MMP) inhibition demonstrates immunomodulatory potential and reduces HCC tumor growth when combined with ablative treatment. Purpose To evaluate the effect of incomplete cryoablation with or without MMP inhibition on the local immune response in residual tumors in a murine HCC model. Materials and Methods Sixty 8- to 10-week-old female BALB/c mice underwent HCC induction with use of orthotopic implantation of syngeneic Tib-75 cells. After 7 days, mice with a single lesion were randomized into treatment groups: (a) no treatment, (b) MMP inhibitor, (c) incomplete cryoablation, and (d) incomplete cryoablation and MMP inhibitor. Macrophage and T-cell subsets were assessed in tissue samples with use of immunohistochemistry and immunofluorescence (cell averages calculated using five 1-µm2 fields of view [FOVs]). C-X-C motif chemokine receptor type 3 (CXCR3)- and interferon γ (IFNγ)-positive T cells were assessed using flow cytometry. Groups were compared using unpaired Student t tests, one-way analysis of variance with Tukey correction, and the Kruskal-Wallis test with Dunn correction. Results Mice treated with incomplete cryoablation (n = 6) showed greater infiltration of CD206+ tumor-associated macrophages (mean, 1.52 cells per FOV vs 0.64 cells per FOV; P = .03) and MMP9-expressing cells (mean, 0.89 cells per FOV vs 0.11 cells per FOV; P = .03) compared with untreated controls (n = 6). Incomplete cryoablation with MMP inhibition (n = 6) versus without (n = 6) led to greater CD8+ T-cell (mean, 15.8% vs 8.29%; P = .04), CXCR3+CD8+ T-cell (mean, 11.64% vs 8.47%; P = .004), and IFNγ+CD8+ T-cell infiltration (mean, 11.58% vs 5.18%; P = .02). Conclusion In a mouse model of HCC, incomplete cryoablation and systemic MMP inhibition showed increased cytotoxic CD8+ T-cell infiltration into the residual tumor compared with either treatment alone. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Gemmete in this issue.

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.

Comparative Analysis of Supratentorial Intraventricular Tumors in Adults and Pediatrics in a Developing Country: Clinicopathological Features, Surgical Management, and Outcomes.

BACKGROUND: Supratentorial intraventricular tumors, encompassing lateral and third ventricular tumors, are uncommon intracranial neoplasms, typically slow-growing and benign, manifesting symptoms only upon reaching a substantial size. This study aims to identify optimal surgical approaches, assess the prevalence and characteristics of these tumors, and evaluate postoperative outcomes among pediatric and adult age groups. METHODS: A retrospective comparative study at a tertiary care hospital from January 2014 to June 2020 included 165 patients (68 pediatrics, 97 adults) meeting inclusion criteria for intraventricular tumor management. Data covered demographic factors, clinical history, neurological assessments, neuroimaging, surgical approaches, histopathological diagnoses, immunohistochemical features, adjuvant therapies, follow-up status, postoperative complications, and morbidity/mortality. RESULTS: Ventricular tumor incidence showed male preponderance in both adults (M:F = 1.2:1) and pediatrics (M:F = 3:1). Lateral ventricles were the most common location. Pediatric cases exhibited more frequent calcifications on computed tomography scans (35.6% vs. 29.5%). Grade II and III tumors were more prevalent in adults within the lateral ventricle (27.1 and 1.9%) compared with pediatrics (6.5 and 8.4%). The third ventricle predominantly featured benign lesions, with pediatric patients experiencing significantly longer hospital stays (16.12 ± 21.94 days vs. 9.58 ± 6.21 days) (p = 0.006). Adults and pediatric patients showed a significant difference in high-grade lateral ventricle tumors (p-value = 0.002*). CONCLUSIONS: Supratentorial ventricular tumors are relatively more prevalent in children than adults, presenting challenges due to size and bleeding risks. Surgical resection is the primary treatment, with a focus on the optimal approach for gross total excision to reduce recurrence risk.

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.

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.

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.

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.

Comparison of Lanthanide Macrocyclic Complexes as 23Na NMR Sensors.

Nuclear magnetic resonance (NMR) agents, composed of paramagnetic lanthanide ions (Ln3+) complexed with negatively charged cyclic chelating agents (Che(n+3)-) forming polyanionic lanthanide complexes (LnChen-), perturb sodium-23 (23Na) signals, a phenomenon which depends sodium ions (Na+) exchanging with LnChen-. We analyzed 23Na shiftability and broadening due to hyperfine and bulk magnetic susceptibility (BMS) effects that arise from LnChen- designs using selective Ln3+ ions (i.e., thulium, Tm3+; gadolinium, Gd3+; and europium, Eu3+) and macrocyclics derived from 1,4,7,10-tetraazacyclododecane (cyclen) [i.e., with phosphonate (DOTP8-) and carboxylate (DOTMA4-) arms] and 1,4,7-triazacyclononane (TACN) [i.e., with phosphonate (NOTP6-) arms]. All LnChen- complexes showed downfield shifts, but Gd3+ and Tm3+ agents, respectively, were dominated by BMS and hyperfine effects, in good agreement with theory. While 23Na shiftability and broadening were minimally affected by pH and competing cations (K+, Ca2+, and Mg2+) within physiological ranges, the 23Na shiftability and broadening were most sensitive to LnChen- concentration in relation to the interstitial Na+ level in vivo. Greatest 23Na shiftability and broadening were obtained with Tm3+ and Gd3+ agents, respectively. While BMS contribution to shiftability was most impacted by the number of unpaired electrons on Ln3+, negative charge on LnChen- regulated Na+ exchange for line broadening. In brain tumor models, TmDOTP5- with 23Na-NMR has been used previously to separate Na+ in intracellular, blood, and interstitial pools, while evidence here shows that GdDOTP5- can distinguish Na+ within intracellular and extracellular (i.e., blood and interstitial) pools. Given the biological importance of Na+ in vivo, future macrocyclic designs of LnChen- should be sought for 23Na-NMR biomedical applications.

BAY 11-7082 inhibits the secretion of interleukin-6 by senescent human microglia.

The accumulation of senescent cells in aged tissues has been implicated in a variety of age-related diseases, including cancer and neurodegenerative disorders. Recent studies have demonstrated a link between age-associated increase of senescent glial cells in the brain and the pathogenesis of Alzheimer's disease (AD). However, there is a lack of in vitro cellular models of senescent human microglia, which significantly limits our approaches to study AD pathogenesis. Here, we show for the first time that ionizing radiation (IR) dose-dependently induces premature senescence in HMC3 human microglial cells. Senescence-associated ß-galactosidase activity, a well-characterized marker of cellular senescence, was substantially increased in irradiated HMC3 cells compared with control cells. Furthermore, we found that phosphorylated p53 levels and p21 expression levels were markedly higher in IR-induced senescent microglia than in control cells. Senescent human microglia exhibited the senescence-associated secretory phenotype (SASP), as evidenced by the increased secretion of pro-inflammatory cytokine interleukin-6 (IL-6). Treatment with an NF-κB inhibitor, BAY 11-7082, inhibits the secretion of IL-6 by senescent HMC3 cells. Collectively, our studies have established an in vitro cellular model of human microglial senescence and suggest that the NF-κB pathway may play a critical role in regulating the SASP of senescent HMC3 cells.

High-resolution pH imaging using ratiometric chemical exchange saturation transfer combined with biosensor imaging of redundant deviation in shifts featuring paramagnetic DOTA-tetraglycinate agents.

Chemical exchange saturation transfer (CEST) and biosensor imaging of redundant deviation in shifts (BIRDS) methods differ respectively by detecting exchangeable and nonexchangeable proton signals by magnetic resonance. Because CEST contrast depends on both temperature and pH, simultaneous CEST and BIRDS imaging can be employed to separate these contributions. Here, we test if high-resolution pH imaging in vivo is possible with ratiometric CEST calibrated for temperature variations measured by BIRDS. Thulium- and europium-based DOTA-tetraglycinate agents, TmDOTA-(gly)4- and EuDOTA-(gly)4- , were used for high-resolution pH mapping in vitro and in vivo, using BIRDS for temperature adjustments needed for a more accurate ratiometric CEST approach. Although neither agent showed pH dependence with BIRDS in vitro in the pH range 6 to 8, each one's temperature sensitivity was enhanced when mixed because of increased redundancy. By contrast, the CEST signal of each agent was affected by the presence of the other agent in vitro. However, pH could be measured more accurately when temperature from BIRDS was detected. These in vitro calibrations with TmDOTA-(gly)4- and EuDOTA-(gly)4- enabled high-resolution pH imaging of glioblastoma in rat brains. It was concluded that temperature mapping with BIRDS can calibrate the ratiometric CEST signal from a cocktail of TmDOTA-(gly)4- and EuDOTA-(gly)4- agents to provide temperature-independent absolute pH imaging in vivo.

Methylated tetra-amide derivatives of paramagnetic complexes for magnetic resonance biosensing with both BIRDS and CEST.

Paramagnetic agents that utilize two mechanisms to provide physiological information by magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging (MRSI) are described. MRI with chemical exchange saturation transfer (CEST) takes advantage of the agent's exchangeable protons (e.g., -OH or -NHx , where 2 ≥ x ≥ 1) to create pH contrast. The agent's incorporation of non-exchangeable protons (e.g., -CHy , where 3 ≥ y ≥ 1) makes it possible to map tissue temperature and/or pH using an MRSI method called biosensor imaging of redundant deviation in shifts (BIRDS). Hybrid probes based upon 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate chelate (DOTA4- ) and its methylated analog (1,4,7,10-tetraazacyclododecane-α, α', α″, α‴-tetramethyl-1,4,7,10-tetraacetate, DOTMA4- ) were synthesized, and modified to create new tetra-amide chelates. Addition of several methyl groups per pendent arm of the symmetrical chelates, positioned proximally and distally to thulium ions (Tm3+ ), gave rise to favorable BIRDS properties (i.e., high signal-to-noise ratio (SNR) from non-exchangeable methyl proton peaks) and CEST responsiveness (i.e., from amide exchangeable protons). Structures of the Tm3+ probes elucidate the influence of methyl group placement on sensor performance. An eight-coordinate geometry with high symmetry was observed for the complexes: Tm-L1 was based on DOTA4- , whereas Tm-L2 and Tm-L3 were based on DOTMA4- , where the latter contained an additional carboxylate at the distal end of each arm. The distance of Tm3+ from terminal methyl carbons is a key determinant for sustaining BIRDS temperature sensitivity without compromising CEST pH contrast; however, water solubility was influenced by introduction of hydrophobic methyl groups and hydrophilic carboxylate. Combined BIRDS and CEST detection of Tm-L2, which features two high-SNR methyl peaks and a strong amide CEST peak, should enable simultaneous temperature and pH measurements for high-resolution molecular imaging in vivo.

Heteroarylation of Congested α-Bromoamides with Imidazo-Heteroarenes and Indolizines via Aza-Oxyallyl Cations: Enroute to Dibenzoazepinone and Zolpidem Analogues.

Herein, we report a highly efficient and unprecedented approach for heteroarylation of congested α-bromoamides via electrophilic aromatic substitution of imidazo-heteroarenes and indolizines under mild reaction conditions (room temperature, metal, and oxidant free). The participation of an in situ generated aza-oxyallyl cation as an alkylating agent is the hallmark of this transformation. The method was readily adapted to synthesize novel imidazo-heteroarene-fused dibenzoazepinone architectures of potential medicinal value.

Carotid doppler indices do not predict fluid responsiveness in mechanically ventilated patients undergoing coronary artery bypass grafting surgery.

BACKGROUND AND AIM OF THE STUDY: This study aimed to determine the predictive value of carotid artery blood flow (CABF), corrected carotid flow time (CFT), and respiratory variation in carotid peak systolic velocity (DVPeakCA) for fluid responsiveness in mechanically ventilated patients undergoing coronary artery bypass grafting (CABG) surgery. It also aimed to correlate each of these indices with changes in stroke volume index (SVI) after a fluid bolus. METHODS: This prospective, interventional, before-after study recruited 45 adult patients undergoing CABG. Following induction of anesthesia, a fluid challenge of 6 ml/kg of a crystalloid solution was delivered over 10 min. Mean arterial pressure (MAP), heart rate (HR), central venous pressure (CVP), CABF, CFT, and DVPeakCA were recorded before and following the intervention. Patients with an increase in SVI of >15% from baseline were considered responders. RESULTS: We had 22 responders and 23 nonresponders. Areas under the receiver operating characteristic (AUROC) curves for the studied indices (CABF, 0.516, CFT, 0.502, and DVPeakCA, 0.671) did not suggest any strong predictive value to detect fluid responsiveness. Similarly, the r values for correlation of these carotid doppler-derived indices, both baseline and as % change from baseline with the % alteration of SVI were all <0.2, which demonstrates a very weak correlation between these variables. CONCLUSIONS: Carotid doppler indices are unreliable to assess fluid responsiveness, and cannot replace invasive methods of analyzing preload optimization. There was no significant correlation between carotid doppler-derived indices and alterations in SVI before and after the fluid bolus.

Coalitionary psychology and group dynamics on social media.

Pietraszewski's model allows understanding group dynamics through the lens of evolved coalitionary psychology. This framework is particularly relevant to understanding group dynamics on social media platforms, where coalitions based on salience of group identity are prominent and generate unique frictions. We offer testable hypotheses derived from the model that may help to shed light on social media behavior.

Diphtheritic Myocarditis Patient with an Impending Upper Airway Compromise.

How to cite this article: Jha AK, Padala SRAN, Parida S, Mishra SK. Diphtheritic Myocarditis Patient with an Impending Upper Airway Compromise. Indian J Crit Care Med 2022;26(10):1153-1154.

Memantine and Ibuprofen pretreatment exerts anti-inflammatory effect against streptozotocin-induced astroglial inflammation via modulation of NMDA receptor-associated downstream calcium ion signaling.

We had previously reported that neuroinflammation and memory impairment associated with intracerebroventricular streptozotocin (ICV STZ) injection in rats was due to glial activation and modulation of the N-methyl-D-aspartate (NMDA) receptor function. However, the exact role of the NMDA receptor and the molecules associated with downstream calcium ion signaling in STZ-induced astroglial activation is not known. Thus, in the present study, Memantine (an NMDA receptor antagonist) and Ibuprofen (an anti-inflammatory drug) were used as the pharmacological tool to investigate the molecular mechanisms involved in STZ-induced astroglial inflammation. We have studied the effect of STZ (100 µM) treatment for 24 h on NMDA receptor subunits (NR1, NR2A, and NR2B) expression and its associated calcium ion regulated molecules calcium/calmodulin-dependent protein kinase II subunit α (CaMKIIα), cyclic AMP-response element-binding (CREB) protein, Calpain, and Caspase 3. We have found a significant increase in the expression of NR1, NR2B, Calpain, and Caspase 3 expression, whereas a decrease in the level of NR2A, CaMKIIα, and CREB protein expression after 24 h of STZ treatment. These results indicate that STZ altered the NMDA receptor subunit expression and its downstream calcium (Ca2+) ion signaling molecules. We have also found that both Memantine (5 µM) and Ibuprofen (200 µM) significantly prevented the STZ-induced change in CaMKIIα, CREB, Calpain, and Caspase 3 expressions in C6 astrocytoma cells. Interestingly, only Memantine (and not Ibuprofen) was able to prevent the changes in NMDA receptor subunit expression in STZ-treated astrocytoma cells. STZ treatment also increased the level of glial fibrillary acidic protein (GFAP), tumor necrosis factor-alpha (TNF-α), inducible nitric oxide synthase (iNOS), and decreased the level of interleukin-10 (IL-10), indicating inflammatory condition, which was restored by both Memantine and Ibuprofen. These results suggest that both Memantine and Ibuprofen exert anti-inflammatory effect against STZ-induced astroglial activation and neuroinflammation via modulation of NMDA receptor-associated downstream calcium signaling cascade. However, only Memantine (not Ibuprofen) was able to revert STZ-induced changes in NMDA receptor subunit expression.

Associations of negative cognitions, emotional regulation, and depression symptoms across four continents: International support for the cognitive model of depression.

BACKGROUND: Cognitive-behavioral therapy (CBT) is one of the most widely tested and empirically supported psychological treatments for depression. Beck and other scholars established the theoretical foundations of CBT among North American populations, yet surprisingly few studies have examined central hypotheses of the cognitive model of depression among people living in non-Western regions. METHODS: In the present study, we used the alignment method to minimize measurement bias to examine several central hypotheses of the cognitive model among adults living on four continents (n = 752): North America (n = 103; female = 29.1%), Europe (n = 404; female = 36.4%), South America (n = 108; female = 18.5%), and Asia (n = 136; female = 19.9%). RESULTS: Depressive symptoms were positively and strongly correlated with negative automatic thoughts about self (ATQ-N), and moderately associated with dysfunctional attitudes (DAS) among people living on the four continents. Further, use of emotional suppression strategies to regulate emotion (ERQ-Suppression) was moderately and positively associated with depressive symptoms among people on all four continents, while use of cognitive-reappraisal (ERQ-Reappraisal) was not systematically associated with depressive symptoms. CONCLUSIONS: Results of this study offer preliminary cross-continental support for foundational hypotheses of the cognitive model of depression. Negative thoughts appear to be associated with depression in all regions of the world, cementing this construct as a hallmark feature of the disorder.

Correction: Mishra, S.K. and Suryaprakash, N. Intramolecular Hydrogen Bonding Involving Organic Fluorine: NMR Investigations Corroborated by DFT-Based Theoretical Calculations: Molecules 2017, 22, 423.

The authors wish to make the following corrections to their paper [...].

Measuring delay discounting in a crowdsourced sample: An exploratory study.

Delay discounting is a measure of preferences for smaller immediate rewards over larger delayed rewards. Discounting has been assessed in many ways; these methods have variably and inconsistently involved measures of different lengths (single vs. multiple items), forced-choice methods, self-report methods, online and laboratory assessments, monetary and non-monetary compensation. The majority of these studies have been conducted in laboratory settings. However, over the past 20 years, behavioral data collection has increasingly shifted online. Usually, these experiments involve completing short tasks for small amounts of money, and are thus qualitatively different than experiments in the lab, which are typically more involved and in a strongly controlled environment. The present study aimed to determine how to best measure future discounting in a crowdsourced sample using three discounting measures (a single shot measure, the 27-item Kirby Monetary Choice Questionnaire, and a one-time Matching Task). We examined associations of these measures with theoretically related variables, and assessed influence of payment on responding. Results indicated that correlations between the discounting tasks and conceptually related measures were smaller than in prior laboratory experiments. Moreover, our results suggest providing monetary compensation may attenuate correlations between discounting measures and related variables. These findings suggest that incentivizing discounting measures changes the nature of measurement in these tasks.