Echocardiographic Evaluation of Left Atrial Mechanics: Function, History, Novel Techniques, Advantages, and Pitfalls

Left atrial (LA) functional analysis has an established role in ass essing left ventricular diastolic function. The current standard echocardiographic parameters used to study left ventricular diastolic function include pulsed-wave Doppler mitral inflow analysis, tissue Doppler imaging measurements, and LA dimension estimation. However, the above-mentioned parameters do not directly quantify LA performance. Deformation studies using strain and strain-rate imaging to assess LA function were validated in previous research, but this technique is not currently used in routine clinical practice. This review discusses the history, importance, and pitfalls of strain technology for the analysis of LA mechanics

Inhibition of Glucose Uptake Blocks Proliferation but Not Cytotoxic Activity of NK Cells

Tumor cells often have very high energy demands. Inhibition of glucose uptake is therefore a possible approach to limit the proliferation and survival of transformed cells. However, immune cells also require energy to initiate and to maintain anti-tumor immune reactions. Here, we investigate the effect of Glutor, an inhibitor of glucose transporters, on the function of human Natural Killer (NK) cells, which are important for the immunosurveillance of cancer. Glutor treatment effectively inhibits glycolysis in NK cells. However, acute treatment with the inhibitor has no effect on NK cell effector functions. Prolonged inhibition of glucose uptake by Glutor prevents the proliferation of NK cells, increases their pro-inflammatory regulatory function and reduces the stimulation-dependent production of IFN-γ. Interestingly, even after prolonged Glutor treatment NK cell cytotoxicity and serial killing activity were still intact, demonstrating that cytotoxic NK cell effector functions are remarkably robust against metabolic disturbances

Aerobic Capacity, Physical Activity and Metabolic Risk Factors in Firefighters Compared with Police Officers and Sedentary Clerks

Background: This study examined the association between the physical work environment and physiological performance measures, physical activity levels and metabolic parameters among German civil servants. A main focus in this study was to examine the group differences rather than measuring the absolute values in an occupational group. Methods: We prospectively examined 198 male German civil servants (97 firefighters [FFs], 55 police officers [POs] and 46 sedentary clerks [SCs]). For each parameter, the groups were compared using a linear regression adjusted for age. Results: The 97 FFs showed a similar maximal aerobic power (VO2max l/min) of 3.17±0.44 l/min compared with the POs, who had a maximal aerobic power of 3.13±0.62 l/min (estimated difference, POs vs. FFs: 0.05, CI: -0.12-0.23, p=0.553). The maximal aerobic power of the FFs was slightly higher than that of the SCs, who had a maximal aerobic power of 2.85±0.52 l/min (-0.21, CI: -0.39-0.04, p=0.018 vs. FFs). The average physical activity (in metabolic equivalents [METS]/week) of the FFs was 3818.8±2843.5, whereas those of the POs and SCs were 2838.2±2871.9 (-808.2, CI: 1757.6-141.2, p=0.095) and 2212.2±2292.8 (vs. FFs: -1417.1, CI: -2302-531.88, p=0.002; vs. POs: -2974.4, CI: -1611.2-393.5, p=0.232), respectively. For the FFs, the average body fat percentage was 17.7%±6.2, whereas it was 21.4%±5.6 for the POs (vs. FFs: 2.75, CI: 0.92-4.59, p=0.004) and 20.8%±6.5 for the SCs (vs. FFs: 1.98, CI: -0.28-4.25, p=0.086; vs. POs: -0.77, CI: 3.15-1.61, p=0.523). The average waist circumference was 89.8 cm±10.0 for the FFs, 97.8 cm±12.4 (5.63, CI: 2.10-9.15, p=0.002) for the POs, and 97.3±11.7 (vs. FFs: -4.89, CI: 1.24-8.55, p=0.009; vs. POs: -0.73, CI: -5.21-3.74, p=0.747) for the SCs. Conclusions: The FFs showed significantly higher physical activity levels compared with the SCs. The PO group had the highest cardiovascular risk of all of the groups because it included more participants with metabolic syndrome; furthermore, the POs had an average of 2.75% higher body fat, lower HDL cholesterol values and higher waist circumferences compared with the FFs and higher LDL cholesterol values compared with the SCs. Our data indicate that sedentary occupations appear to be linked to obesity and metabolic syndrome in middle-aged men

Physical activity, cardiorespiratory fitness and carotid intima thickness:Sedentary occupation as risk factor for atherosclerosis and obesity

OBJECTIVE: The influence of occupational physical activity on markers of atherosclerosis, prevalence of metabolic syndrome and physical performance has been understudied in current literature. Main aim of this study was to examine the association between physical work environment and physiological performance measures, physical activity, metabolic parameters and carotid atherosclerosis among German career firefighters and sedentary clerks. PATIENTS AND METHODS: We prospectively examined and recruited 143 male German civil servants (97 firefighters [FFs], and 46 sedentary clerks [SCs]). Correlation for each parameter for the groups were compared using a linear regression model adjusted for age. RESULTS: 97 firefighters (FFs) showed higher maximal aerobic power (VO2max ) of 3.17 ± 0.44 L/min compared to 46 sedentary clerks (SCs) 2.85 ± 0.52 L/min (-0.21 CI -0.39-0.04, p = 0.018). Physical activity (PA, in METS/week) in FFs was 3953 ± 2688 and in SC 2212 ± 2293 (-1791.86 CI -2650-934, p = 0.000). Body fat was 17.7 ± 6.2% in FFs and in SCs 20.8 ± 6.5% (1.98 CI -0.28-4.25, p = 0.086). Waist circumference was 89.8 ±10.0 cm in FFs and in SCs 97.3 ± 11.7 (-4.89 CI 1.24-8.55, p = 0.009). Carotid intima media thickness (IMT) showed significant difference for the left carotid artery 0.69 ± 0.19 mm in FFs vs. SCs 0.81 ± 0.20 (0.07 CI 0.01-0.14, p = 0.030). Metabolic syndrome was found in 12 out of 98 FFs (13.4%), and in 14 out of 46 SCs (30.43%). CONCLUSIONS: FFs showed significantly higher physical activity levels compared with the SCs. SCs had higher cardiovascular risk profile, higher prevalence of metabolic syndrome, higher waist circumference and significantly higher IMT than FFs. In conclusion, sedentary occupations have higher cardiovascular risk secondary to accelerated atherosclerosis

Metabolic requirements of NK cells during the acute response against retroviral infection

Natural killer (NK) cells are important early responders against viral infections. Changes in metabolism are crucial to fuel NK cell responses, and altered metabolism is linked to NK cell dysfunction in obesity and cancer. However, very little is known about the metabolic requirements of NK cells during acute retroviral infection and their importance for antiviral immunity. Here, using the Friend retrovirus mouse model, we show that following infection NK cells increase nutrient uptake, including amino acids and iron, and reprogram their metabolic machinery by increasing glycolysis and mitochondrial metabolism. Specific deletion of the amino acid transporter Slc7a5 has only discrete effects on NK cells, but iron deficiency profoundly impaires NK cell antiviral functions, leading to increased viral loads. Our study thus shows the requirement of nutrients and metabolism for the antiviral activity of NK cells, and has important implications for viral infections associated with altered iron levels such as HIV and SARS-CoV-2

IFI16 Targets the Transcription Factor Sp1 to Suppress HIV-1 Transcription and Latency Reactivation

The interferon γ-inducible protein 16 (IFI16) is known as immune sensor of retroviral DNA intermediates. We show that IFI16 restricts HIV-1 independently of immune sensing by binding and inhibiting the host transcription factor Sp1 that drives viral gene expression. This antiretroviral activity and ability to bind Sp1 require the N-terminal pyrin domain and nuclear localization of IFI16, but not the HIN domains involved in DNA binding. Highly prevalent clade C HIV-1 strains are more resistant to IFI16 and less dependent on Sp1 than other HIV-1 subtypes. Furthermore, inhibition of Sp1 by IFI16 or pharmacologically by Mithramycin A suppresses reactivation of latent HIV-1 in CD4+ T cells. Finally, IFI16 also inhibits retrotransposition of LINE-1, known to engage Sp1, and murine IFI16 homologs restrict Friend retrovirus replication in mice. Thus, IFI16 restricts retroviruses and retrotransposons by interfering with Sp1-dependent gene expression, and evasion from this restriction may facilitate spread of HIV-1 subtype C