Enevoldsenweeks7584

Growth hormone treatment was introduced in the 1950s to address growth disturbances and metabolic abnormalities. Hundreds of thousands of children have been treated, with gradual expansion of treatment indications. From initially being offered only to patients with severe growth hormone deficiency, today many children are treated for conditions in which the associated short stature is not primarily thought to be due to deficient endogenous growth hormone secretion. This review discusses the history, physiology and safety of growth hormone treatment, with focus on the long-term risks of mortality, cardiovascular morbidity and cancer. Conclusion Continuous follow-up is needed to increase our knowledge of the long-term treatment safety.

To analyze how left ventricular (LV) remodeling and hypertrophy geometry evolve after surgical aortic valve replacement (SAVR) in octogenarian patients, and identify potential sex-related differences and implications for long-term outcomes.

In 170 patients with aortic stenosis ([AS], age 80±4years, 59% women), hypertrophy geometry and remodeling (LV index) were reanalyzed one year post-SAVR. The six-year outcomes were evaluated.

Pre-SAVR, 65% of the women and 38.6% of the men (P<.001) showed adaptive remodeling. Concentric hypertrophy was prevalent in adaptive remodeling, and mixed and dilated hypertrophy were more prevalent in maladaptive remodeling. At one year, the remodeling patterns and sex distribution were similar to those observed pre-SAVR, but the LV index decreased in women and increased in men (P<.0001). Women with adaptive remodeling had a higher incidence of persistent concentric hypertrophy with higher LV filling pressures. Long-term survival was better in women and worse in men with adaptive remodeling (P=.039). Men with adaptive remodeling and men with concentric hypertrophy had the highest risk of cardiac death. This risk was similar between sexes for patients with maladaptive remodeling and dilated hypertrophy. Women with LV ejection fraction >55% had a lower risk of cardiac death than men.

The long-term outcomes of SAVR differ between sexes in older patients with AS and adaptive LV remodeling. The LV index facilitates studying the pathways of adaptation to AS. The follow-up shifts help explain the sex differences in long-term outcomes post-SAVR. Concentric hypertrophy is associated with the highest risk of cardiac death in men.

The long-term outcomes of SAVR differ between sexes in older patients with AS and adaptive LV remodeling. The LV index facilitates studying the pathways of adaptation to AS. The follow-up shifts help explain the sex differences in long-term outcomes post-SAVR. Concentric hypertrophy is associated with the highest risk of cardiac death in men.Immunometabolism is rising as an intriguing topic that reveals the connection between immune cell function and metabolic processes. Especially, fatty acid metabolism plays an essential role in the dendritic cells (DCs) during the differentiation and maturation period. We questioned whether regulation of acetyl-CoA carboxylases 1 and 2-(ACC1/2), the core enzymes of fatty acid synthesis (FAS), would control DC function. Here, we report that blocking ACC1/2 to prevent FAS during DC maturation switched their cellular metabolism into fatty acid oxidation to fuel oxidative phosphorylation. This action turned DCs to utilize exogenous fatty acids to sustain their basal energy demand and maintain a stable cellular respiration rate. Coincidentally, under the ACC1/2 inhibitor treatment, LPS-treated DCs exhibited a semimaturation phenotype with a maturation-resistance feature, with decreased expression of costimulatory molecules including CD86 and CD40, along with the reduction of IL-12 and IL-6. The migratory capability of DCs has been known to relate to the glycolysis pathway, and here we showed that the ACC1/2 blockade did not affect the expression of CCR7 and DC migration. Furthermore, we found that under the ACC1/2 blocking condition, DCs pulsed with OVA failed to activate OVA-specific CD4+ T cell proliferation even though their antigen uptake capacity was intact. Together, our data suggest ACC1/2 as a promising target to control DC fate.Protective cytotoxic and proinflammatory cytokine responses by NK cells impact the outcome of infections by Toxoplasma gondii, a common parasite in humans and other vertebrates. However, T. gondii can also sequester within NK cells and downmodulate their effector functions. Recently, the implication of GABA signaling in infection and inflammation-related responses of mononuclear phagocytes and T cells has become evident. Yet, the role of GABAergic signaling in NK cells has remained unknown. Here, we report that human and murine NK cells synthesize and secrete GABA in response to infection challenge. Bioactive Compound Library Parasitized NK cells secreted GABA, whereas activation stimuli, such as IL-12/IL-18 or parasite lysates, failed to induce GABA secretion. GABA secretion by NK cells was associated to a transcriptional up-regulation of GABA synthesis enzymes (glutamate decarboxylases [GAD65/67]) and was abrogated by GAD inhibition. Further, NK cells expressed GABA-A receptor subunits and GABA signaling regulators, with transcriptional modulations taking place upon challenge with T. gondii. Exogenous GABA and GABA-containing supernatants from parasitized dendritic cells (DCs) impacted NK cell function by reducing the degranulation and cytotoxicity of NK cells. Conversely, GABA-containing supernatants from NK cells enhanced the migratory responses of parasitized DCs. This enhanced DC migration was abolished by GABA-A receptor antagonism or GAD inhibition and was reconstituted by exogenous GABA. Jointly, the data show that NK cells are GABAergic cells and that GABA hampers NK cell cytotoxicity in vitro. We hypothesize that GABA secreted by parasitized immune cells modulates the immune responses to T. gondii infection.

We aimed to define specific reference intervals (RIs) for eleven biomarkers including inflammatory and oxidative stress biomarkers, liver and renal function tests in a healthy Iranian adult population for the first time.

CLSI Ep28-A3 guidelines were then used to calculate accurate age- and sex- as well as BMI-specific RIs.

RIs for studied biomarkers showed no significant age and sex-specific differences, except for uric acid, which had higher concentrations in men when compared to women. Additionally, after partitioning the participants based on the body mass index (BMI) with a cutoff point of 25 kg/m

, only the levels of hs-CRP were positively associated with higher BMI (RI for BMI>25 0.51 - 7.85 mg/L and for BMI< 25 0.40 - 4.46 mg/L). RI for PAB and anti hsp-27 were reported 4.69-155.36 HK and 0.01-0.70 OD in men and women aged 35 to 65 years old.

Partitioning by sex and BMI was only required for uric acid and hs-CRP, respectively, while other biomarkers required no partitioning. These results can be expected to valuably contribute to improve laboratory test result interpretation in adult for improved monitoring of various diseases in the Iranian population.