LC3-associated phagocytosis in bone marrow macrophages suppresses acute myeloid leukemia progression through STING activation

The bone marrow (BM) microenvironment regulates acute myeloid leukemia (AML) initiation, proliferation, and chemotherapy resistance. Following cancer cell death, a growing body of evidence suggests an important role for remaining apoptotic debris in regulating the immunologic response to and growth of solid tumors. Here, we investigated the role of macrophage LC3–associated phagocytosis (LAP) within the BM microenvironment of AML. Depletion of BM macrophages (BMMs) increased AML growth in vivo. We show that LAP is the predominate method of BMM phagocytosis of dead and dying cells in the AML microenvironment. Targeted inhibition of LAP led to the accumulation of apoptotic cells (ACs) and apoptotic bodies (ABs), resulting in accelerated leukemia growth. Mechanistically, LAP of AML-derived ABs by BMMs resulted in stimulator of IFN genes (STING) pathway activation. We found that AML-derived mitochondrial damage–associated molecular patterns were processed by BMMs via LAP. Moreover, depletion of mitochondrial DNA (mtDNA) in AML-derived ABs showed that it was this mtDNA that was responsible for the induction of STING signaling in BMMs. Phenotypically, we found that STING activation suppressed AML growth through a mechanism related to increased phagocytosis. In summary, we report that macrophage LAP of apoptotic debris in the AML BM microenvironment suppressed tumor growth.     

Performance of a histidine-rich protein 2 rapid diagnostic test, Paracheck Pf®, for detection of malaria infections in Ugandan pregnant women

Improved laboratory diagnosis is critical to reduce the burden of malaria in pregnancy. Peripheral blood smears appear less sensitive than Plasmodium falciparum histidine-rich protein 2-based rapid diagnostic tests (RDTs) for placental malaria infections in studies conducted at delivery. In this study, 81 women in Uganda in the second or third trimester of pregnancy were followed-up until delivery. At each visit, peripheral blood was tested by blood smear, RDT, and nested species-specific polymerase chain reaction (PCR). Sensitivity and specificity of the tests was calculated with PCR, which detected 22 infections of P. falciparum, as the gold standard. The sensitivity and specificity of blood smears were 36.4% (95% confidence interval [CI] = 18.0-59.2%) and 99.6% (95% CI = 97.7-100%), respectively. The corresponding values for RDT were 31.8% (95% CI = 14.7-54.9%) and 100% (95% CI = 98.3-100%). The RDTs could replace blood smears for diagnosis of malaria in pregnancy by virtue of their relative ease of use. Field-based sensitive tests for malaria in pregnancy are urgently needed.     

Whortleberry protects kidney against the cisplatin-induced nephrotoxicity: an experimental study

Purpose: This study investigated the antioxidant effects of whortleberry against cisplatin-induced nephrotoxicity in rats.

Material and methods: This study included 48 female Sprague–Dawley rats weighing 263.68?±?8.29?g. The rats were divided into the following six groups, with eight rats in each group: control, ethanol control, whortleberry control, cisplatin control, 16?mg/kg cisplatin +100?mg/kg whortleberry, and 16?mg/kg cisplatin +200?mg/kg whortleberry groups. Biochemical analysis was performed by measuring total oxidant status and total antioxidant status, histopathological analysis was performed by calculating proximal and distal tubule areas (μm²), and immunohistochemical analysis was performed by determining anti-Caspase-3 immunostaining. Differences among the groups were examined using one-way analysis of variance, and p?Results: Cisplatin treatment decreased the total antioxidant status and increased the total oxidant status and Caspase-3 level. Moreover, it resulted in the dilatation, vacuolization and loss of tubular epithelial cells; and glomerular degeneration and edema in the kidney tissues (p?p?Conclusions: Our results indicate that the antioxidant effects of the whortleberry decrease cisplatin-associated nephrotoxicity.     

Role of self-efficacy and behaviour change

Behaviour change is an important concept in relation to health promotion and disease prevention. Self-efficacy has been identified as an important determinant of health behaviour, future health behaviour and health behaviour change. In order to effectively facilitate behaviour change, it is essential that interventions are research based, and emphasize the utility of theory in practice. The effective practice of health promotion and disease prevention requires a full understanding of the processes of patient behaviour. This article presents the role of the nurse in influencing health-related behaviour change. Self-efficacy and related but distinct theories that underpin behaviour change are discussed. The empirical evidence that supports the link between self-efficacy and predictions of health behaviours is also examined.     

Early Myocardial Functional Alterations in Patients with Obstructive Sleep Apnea Syndrome

Background: There is limited information regarding myocardial alterations in patients with obstructive sleep apnea syndrome (OSAS) in the absence of pulmonary and cardiac comorbidity. In this study, we aimed to evaluate potential myocardial alterations of these patients and investigate the possible effects of OSAS-related pathological variations on left and right ventricular functions. Methods: We studied 107 consecutive patients who were referred to our sleep laboratory for clinically suspected OSAS and 30 controls without any history or symptoms of sleep-related disorders. Severity of OSAS was quantified by polysomnography. Patients with apnea–hypopnea index (AHI) < 5 were included in the OSAS (−) group (Group 1, n = 22). Subjects with AHI ≥ 5 were considered as OSAS and classified according to their AHI as mild-to-moderate (AHI ≥ 5 and AHI < 30) (Group 2, n = 45) and severe (AHI ≥ 30) OSAS groups (Group 3, n = 40). Conventional M-mode, 2D, and Doppler mitral inflow parameters, tissue Doppler velocities, myocardial peak systolic strain, and strain rate values of various segments were measured and compared between groups. Results: Patients with OSAS displayed impairment of left ventricular diastolic function compared with controls. There were no significant differences between groups regarding parameters reflecting left ventricular systolic function. Myocardial strain analysis demonstrated significant decrement regarding apical right ventricular longitudinal peak systolic strain and strain rate values between groups in relation to the severity of OSAS. Conclusions: Patients with OSAS display a regional pattern of right ventricular dysfunction correlated with the severity of disease.