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Caloric restriction and ketogenic diets may modify the progression of neurological disorders, including HIV-associated neurological disorders and Alzheimer’s disease, in part by influencing astrocyte function. This study examines how metabolic substrate availability affects metabolic processes and gene expression in human astrocytes. We exposed astrocytes to the glycolysis inhibitor 2-deoxyglucose (2-DG), to mimic caloric restriction, prior to stimulation with interleukin-1β and measured extracellular flux using the Seahorse ® platform. We next analyzed gene expression and chromatin accessibility changes using RNA-sequencing and ATAC-sequencing, respectively. Finally, we tested the effects of glucose deprivation and the ketone body β-hydroxybutyrate (BHB) on inflammatory gene expression. 2-DG reduced oxygen consumption rate and extracellular acidification rate in the presence of IL-1β, while concomitantly decreasing expression of pro-inflammatory cytokines TNF, IL-6, and C3. These changes were linked to altered chromatin structure. The metabolic substrate β-hydroxybutyrate was associated with reduced cytokine expression compared to glucose. Inhibition of glycolysis attenuated IL-1β-induced inflammation and gene expression changes and altered chromatin architecture. Both glucose deprivation and BHB treatment reduced inflammatory cytokine expression, with additive effects when combined with 2-DG. These results suggest that targeting glycolysis could provide therapeutic strategies for treating neurological diseases through modulation of astrocyte-driven inflammation.

Purpose Levothyroxine (LEV) monotherapy cannot completely improve cognitive and behavioral impairments induced by hypothyroidism, whereas a combination therapy of exercise and LEV may ameliorate these deficits. This study aimed to determine the effects of mild‐intensity forced exercise and LEV treatment on the anxiety profile and cognitive functions in male offspring of hypothyroid dams. Method Twenty‐four female rats (mothers) were randomly divided into sham (healthy) and hypothyroidism groups and then placed with male rats to mate. The presence of vaginal plaque confirmed pregnancy (gestational day, GD 0). 6‐propyl‐2‐thiouracil (PTU, 100 ppm) was added to the drinking water of the hypothyroidism group from GD 6 to the 21st postnatal day (PND). The sham group received tap water. On PND 21, serum T4 levels of mothers, and 10 pups were measured to confirm hypothyroidism. Sixty‐four male pups were left undisturbed for 30 days and then were divided into eight groups that received saline or LEV (50 μg/kg, i.p.) with or without forced mild‐intensity exercise. After 14 days of interventions, anxiety‐like behaviors, spatial learning and memory, and hippocampal brain‐derived neurotrophic factor (BDNF) levels were evaluated. Finding A pre and postnatal PTU‐induced model of hypothyroidism increased anxiety‐like behaviors, impaired spatial learning and memory, and decreased hippocampal BDNF levels in male offspring rats. LEV alone increased BDNF levels and improved spatial learning. Exercise alone increased BDNF levels, improved spatial learning and memory, and decreased anxiety‐like behaviors. Exercise plus LEV more effectively improved anxiety‐like behaviors and spatial learning than exercise or LEV alone. Conclusion Practically, these pre‐clinical findings highlight the importance of the combination of exercise and LEV regimen in treating patients with hyperthyroidism. A maternal PTU‐induced hypothyroidism model led to increased anxiety‐like behaviors, impaired spatial navigation, and reduced hippocampal BDNF levels in male offspring rats. Levothyroxine alone increased BDNF levels and improved spatial learning, while exercise alone boosted BDNF levels, enhanced spatial learning and memory, and reduced anxiety‐like behaviors. The combination of exercise and levothyroxine was more effective in improving anxiety‐like behaviors and spatial learning than either treatment alone.

Human immunodeficiency virus (HIV) infection is often associated with chronic inflammation and cognitive dysfunction in people living with HIV (PWH). The nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome plays a crucial role in the secretion of pro-inflammatory cytokines, specifically interleukin (IL)-18 and IL-1β. Cannabis use and certain phytocannabinoids, such as cannabidiol (CBD), may provide therapeutic benefits in conditions associated with chronic inflammation. In this cross-sectional study, we investigated the relationship between cannabis use and -related gene expression in monocyte-derived macrophages (MDMs) from PWH (n = 43) and people without HIV (PWoH; n = 22). Participants were categorized as naïve, moderate, or daily cannabis users. Donor-derived MDMs were treated with CBD (30 μM), IL-1β (20 ng/mL), or CBD + IL-1β for 24 hours to examine effects on -related gene expression. Gene expression data were analyzed using one-way and two-way ANOVA with Holm-Sidak's multiple comparisons tests. Correlations between gene expression and clinical parameters were assessed using Pearson's correlation coefficient. Statistical significance was determined at p < 0.05. MDMs without treatment from PWH exhibited 83% higher mRNA expression compared to MDMs from PWoH. Furthermore, MDMs without treatment from moderate cannabis users expressed 61% less mRNA compared to naïve users, and MDMs from daily users expressed a 64% increase in expression compared to moderate users. Additionally, MDMs treated with CBD and IL-1β showed a 22% decrease in mRNA expression compared to IL-1β treated MDMs. When treated with CBD and IL-1β, we observed a significant increase in both (3-fold, p < 0.01) and (2-fold, p < 0.01) expression compared to vehicle. The relationship between mRNA expression in MDMs and global deficit scores in PWH not using cannabis was inverse to that relationship in PWH using cannabis. Overall, these findings suggest that CBD, as consumed through cannabis use, may mitigate NLRP3 activation in PWH, potentially offering therapeutic benefits for chronic inflammation. However, the unexpected effects on downstream cytokine mRNA expression, combined with product heterogeneity, underscore the need for future mechanistic studies to fully delineate cannabinoid-inflammasome interactions in the context of HIV.

Triggering receptor expressed on myeloid cells 2 (TREM2) is involved in neuroinflammation and HIV-associated neurocognitive impairment (NCI). People with HIV (PWH) using cannabis exhibit lower inflammation and neurological disorders. We hypothesized that TREM2 dysfunction mediates HIV neuropathogenesis and can be reversed by cannabinoids. EcoHIV-infected wildtype (WT) and TREM2R47H mutant mice were used to study HIV’s impact on TREM2 and behavior. TREM2 and related gene expressions were examined in monocyte-derived macrophages (MDMs) from PWH (n = 42) and people without HIV (PWoH; n = 19) with varying cannabis use via RNA sequencing and qPCR. Differences in membrane-bound and soluble TREM2 (sTREM2) were evaluated using immunocytochemistry (ICC) and ELISA. EcoHIV increased immature and C-terminal fragment forms of TREM2 in WT mice but not in TREM2R47H mice, with increased IBA1 protein in TREM2R47H hippocampi, correlating with worse memory test performance. TREM2 mRNA levels increased with age in PWoH but not in PWH. Cannabidiol (CBD) treatment increased TREM2 mRNA alone and with IL1β. RNA-seq showed the upregulation of TREM2-related transcripts in cannabis-using PWH compared to naïve controls. IL1β increased sTREM2 and reduced membrane-bound TREM2, effects partially reversed by CBD. These findings suggest HIV affects TREM2 expression modulated by cannabis and CBD, offering insights for therapeutic strategies.

Background/Objectives: HIV-associated neurocognitive impairment (NCI) remains a prevalent issue among people with HIV (PWH) despite advancements in antiretroviral therapy (ART). The pathogenesis of HIV-associated NCI is linked to chronic neuroinflammation caused by HIV, even in those with successful viral suppression. Growth Differentiation Factor 15 (GDF15), a protein involved in inflammatory and metabolic stress responses, has emerged as a key player and potential biomarker for various neurological conditions. This study investigates the relationship between GDF15 expression and HIV-associated NCI. Methods: PWH from the California NeuroAIDS Tissue Network (CNTN) underwent comprehensive neuropsychological exams within 12 months before death and were categorized based on cognitive performance. We examined GDF15 levels in their CSF (Cerebrospinal Fluid) and brain tissues using immunoblotting, immunohistochemistry, double immunolabeling, and ELISA. Results: The cohort was of a similar age across HIV-associated NCI statuses (mean = 40.5), with a predominance of males (77%). The mean plasma viral load was 3.56 log10 copies/mL for Neurocognitively Unimpaired (NUI) PWH and 5.38 log10 copies/mL for people with HIV-associated NCI. GDF15 protein levels were significantly elevated in the frontal cortices of PWH with NCI compared to NUI PWH. Conclusions: The findings indicate that GDF15 may play a role in the pathogenesis of HIV-associated NCI, possibly through neuroinflammatory mechanisms. The strong association between GDF15 levels and cognitive impairment severity suggests its potential as a biomarker for the early detection and monitoring of NCI in PWH.

Distal sensory polyneuropathy (DSP) and distal neuropathic pain (DNP) remain significant challenges for older people with HIV (PWH), necessitating enhanced clinical attention. HIV and certain antiretroviral therapies (ARTs) can compromise mitochondrial function and impact mitochondrial DNA (mtDNA) replication, which is linked to DSP in ART-treated PWH. This study investigated mtDNA, mitochondrial fission and fusion proteins, and mitochondrial electron transport chain protein changes in the dorsal root ganglions (DRGs) and sural nerves (SuNs) of 11 autopsied PWH. In antemortem standardized assessments, six had no or one sign of DSP, while five exhibited two or more DSP signs. Digital droplet polymerase chain reaction was used to measure mtDNA quantity and the common deletions in isolated DNA. We found lower mtDNA copy numbers in DSP+ donors. SuNs exhibited a higher proportion of mtDNA common deletion than DRGs in both groups. Mitochondrial electron transport chain (ETC) proteins were altered in the DRGs of DSP+ compared to DSP− donors, particularly Complex I. These findings suggest that reduced mtDNA quantity and increased common deletion abundance may contribute to DSP in PWH, indicating diminished mitochondrial activity in the sensory neurons. Accumulated ETC proteins in the DRG imply impaired mitochondrial transport to the sensory neuron’s distal portion. Identifying molecules to safeguard mitochondrial integrity could aid in treating or preventing HIV-associated peripheral neuropathy.

Furthermore, we found a left-sided costovertebral angle (CVA) tenderness andmass-like lesion on the left lower quadrant.Focused Assessment with Sonography for Trauma (FAST) showed left posterior retroperitoneal free fluid and it led to perform an abdominal CT scan.The CT scan also showed a blunted costophrenic angle which was most probably caused by Covid-19 and a left retroperitoneal collection by 220·105·115 mm dimensions obliterating the Left Rubrum Quadratus and Psoas and moving the left Kidney and Colon. [fig2] After receiving initial treatments, the patient was closely monitored by the surgeons to evaluate the patient's condition for the potential surgery. [...]we administrated tranexamic acid and held antiplatelet due to the Abdominal Hematoma and coagulation problems. Conclusion To sum up our report, although respiratory system involvement is the most remarkable manifestation of COVID 19 infection, a number of other presentations could be attributed to the infection which might be even fatal. [...]special attention to other manifestations is essential for confronting the pandemic.

On admission, his vital signs indicated a body temperature of 38.1°C, BP: 140/90 mmHg, PR: 100, and a plunged O2 Saturation into 68% that could be corrected to 97% by a 10 lit/min reserve bag. According to the findings in physical examination, the patient immediately underwent a pulmonary CT Angiography (CTA) in order to rule out possible pulmonary thromboembolism (PTE). [...]furthered studies are needed to have a better sight on the manifestations of the new disease in order to take appropriate measurements to prevent lung tissue injury during involvement and spread of other infections as well.

Metal oxide heterostructures have gained huge attention in the energy storage applications due to their outstanding properties compared to pristine metal oxides. Herein, magnetic Fe 2 O 3 @SnO 2 heterostructures were synthesized by the sol–gel electrospinning method at calcination temperatures of 450 and 600 °C. XRD line profile analysis indicated that fraction of tetragonal tin oxide phase compared to rhombohedral hematite was enhanced by increasing calcination temperature. FESEM images revealed that hexagonal nanoplatelets of Fe 2 O 3 were hierarchically anchored on SnO 2 hollow nanofibers. Optical band gap of heterogeneous structures was increased from 2.06 to 2.40 eV by calcination process. Vibrating sample magnetometer analysis demonstrated that increasing calcination temperature of the samples reduces saturation magnetization from 2.32 to 0.92 emu g -1 . The Fe 2 O 3 @SnO 2 -450 and Fe 2 O 3 @SnO 2 -600 nanofibers as active materials coated onto Ni foams (NF) and their electrochemical performance were evaluated in three and two-electrode configurations in 3 M KOH electrolyte solution. Fe 2 O 3 @SnO 2 -600/NF electrode exhibits a high specific capacitance of 562.3 F g -1 at a current density of 1 A g -1 and good cycling stability with 92.8% capacitance retention at a high current density of 10 A g -1 after 3000 cycles in three-electrode system. The assembled Fe 2 O 3 @SnO 2 -600//activated carbon asymmetric supercapacitor device delivers a maximum energy density of 50.2 Wh kg -1 at a power density of 650 W kg -1 . The results display that the Fe 2 O 3 @SnO 2 -600 can be a promising electrode material in supercapacitor applications.

Individuals undergo bariatric surgery to achieve significant weight loss or improvement of comorbidities. Early identification of patients at risk for suboptimal clinical response is critical to enable timely intervention. This study evaluated the performance of TWL percentiles for predicting suboptimal clinical response after one-anastomosis gastric bypass (OAGB), Roux-en-Y gastric bypass (RYGB), and sleeve gastrectomy (SG). This retrospective cohort study included 5780 individuals undergoing bariatric surgery from 2008 to 2020. Suboptimal clinical response was defined as a %TWL < 20 at the first follow-up visit occurring between 24 and 36 months after surgery. The mean age of participants was 37 years for SG and 40 years for both OAGB and RYGB, with the majority being female (75–84%). From three months post-surgery, patients with suboptimal clinical response were consistently concentrated below the 25th percentile, suggesting this threshold may serve as a general early warning sign. Six months post-surgery, the 23rd percentile for SG, 29th for RYGB, and 33rd for OAGB emerged as the key predictive thresholds. TWL percentiles offer a valuable tool for predicting suboptimal clinical response. Incorporating TWL percentile monitoring into routine postoperative care may support timely detection, enabling earlier intervention with targeted strategies for better long-term outcomes.