Phagocytosis of Hemozoin (Native and Synthetic Malaria Pigment), and Plasmodium falciparum Intraerythrocyte-Stage Parasites by Human and Mouse Phagocytes

Hemozoin, the detoxification product of hemoglobin heme, piles up as electron-dense material in the food vacuole (FV) of intraerythrocytic malaria parasites (malaria pigment). In infected individuals, pigment is internalized by both circulating and resident phagocytes, thus modulating their functions. Synthetic beta-hematin, prepared in vitro from hematin (ferriprotoporphyrin IX hydroxide) in acidic condition, is spectroscopically identical to hemozoin. In this electron microscopy study, native and synthetic hemozoin also prove to be morphologically indistinguishable (large polygonal crystals with apparent transverse banding) and to undergo the same process when internalized by phagocytes (primarily a direct uptake of crystals, similar to what is described for asbestos fibers). On the contrary,whole parasites appear to follow a classical endocytic pathway. This suggests that there may be differences between the ingestion of free particles and whole parasites in terms of modulation of phagocytes' functions.     

Electron Microscopy Analysis of Early Localization of Cisplatin in Ovarian Carcinoma Cells

Taking advantage of the electron-dense nature of platinum, in this study the authors used an electron microscopy approach to investigate the cellular localization of cisplatin in an ovarian carcinoma cell line. Platinum spots were detected in contact with the plasma membrane and the nuclear envelope as well as in the cytoplasm and nuclear matrices. Contact with the plasma membrane was through a single blunt contact or spanning through the membrane. No sequestration in intracellular vescicles was observed, thereby supporting that phagocytosis and receptor-mediated endocytosis were not occurring. A molecular analysis indicated lack of expression of aquaporin 9, thus excluding its involvement in the membrane translocation of cisplatin. The present data suggest that cisplatin rapidly accumulates in the cell through endocytosis-independent membrane translocation and are consistent with passive diffusion.     

Gut microbiota imbalance and chaperoning system malfunction are central to ulcerative colitis pathogenesis and can be counteracted with specifically designed probiotics: a working hypothesis

In this work, we propose that for further studies of the physiopathology and treatment for inflammatory bowel diseases, an integral view of the conditions, including the triad of microbiota–heat shock proteins (HSPs)–probiotics, ought to be considered. Microbiota is the complex microbial flora that resides in the gut, affecting not only gut functions but also the health status of the whole body. Alteration in the microbiota’s composition has been implicated in a variety of pathological conditions (e.g., ulcerative colitis, UC), involving both gut and extra-intestinal tissues and organs. Some of these pathologies are also associated with an altered expression of HSPs (chaperones) and this is the reason why they may be considered chaperonopathies. Probiotics, which are live microorganisms able to restore the correct, healthy equilibrium of microbiota composition, can ameliorate symptoms in patients suffering from UC and modulate expression levels of HSPs. However, currently probiotic therapy follows ex-adiuvantibus criteria, i.e., treatments with beneficial effects but whose mechanism of action is unknown, which should be changed so the probiotics needed in each case are predetermined on the basis of the patient’s microbiota. Consequently, efforts are necessary to develop diagnostic tools for elucidating levels and distribution of HSPs and the microbiota composition (microbiota fingerprint) of each subject and, thus, guide specific probiotic therapy, tailored to meet the needs of the patient. Microbiota fingerprinting ought to include molecular biology techniques for sequencing highly conserved DNA, e.g., genes encoding 16S RNA, for species identification and, in addition, quantification of each relevant microbe.     

The effect of variability in maturational tempo and midparent height on variability in linear body measurements

Background: Information on the effect of variability in maturational tempo on variability in height attained at the same age is not readily available.

Aim: The study obtained this information from the data of the First Zurich Longitudinal Study.

Subjects and methods: Yearly measurements of standing height, sitting height and leg length, yearly assessments of bone age (RUS (Radius, Ulna and Short bones), TW3 method) and midparent height for 232 children from the First Zurich Longitudinal Growth Study are included in a correlational analysis.

Results: The course of the squared correlations of standing height, sitting height and leg length with attained RUS bone age, midparent height and both as a function of age are presented.

Conclusions: During puberty, up to 50% of the height variation in boys and 40% in girls is explained by maturational tempo.

Résumé. Arrière plan: L’information concernant l’effet de la variabilitè du rythme de la maturation sur celle de la stature á un âge donnè, n’est pas disponible.

But: Cette ètude a obtenu de l’information á partir de la première ètude longitudinale de Zurich.

Sujet0s y mèthodes: Une analyse de corrèlation est effectuèe á partir de mensurations annuelles de la stature, de la taille assis et de la longueur de la jambe, de contröles annuels de l’âge osseux (RUS, TW3) et de la stature mèdiale des parents pour 232 enfants de la première ètude de croissance de Zurich.

Résultats: On prèsente les valeurs des carrès des corrèlations pour la stature, la taille assis et la longueur de la jambe avec l’âge osseux atteint (RUS radius, ulna et os courts), avec la stature mèdiale des parents et les deux comme une fonction de l’âge.

Conclusions: Pendant la pubertè, jusqu’á 50% de la variation de la stature des garons et 40% de celle des filles, sont expliquès par le rythme de maturation.

Zusammenfassung. Hintergrund: Informationen über die Auswirkungen von Schwankungen im reifungsbedingten Wachstumstempo auf unterschiedliche im gleichen Alter erzielte Größen sind nicht in geeigneter Form verfügbar.

Ziel: Die vorliegende Arbeit versucht, Informationen zur angesprochenen Problematik aus den Daten der ersten Züricher Longitudinalstudie zu erlangen.

Inhalt und Methodik: Die jährlichen Daten aus Größenmessungen in den Positionen Stehen, Sitzen sowie Beinlänge und die jährlichen Bewertungsergebnisse der Knochenalter (RUS, TW3) als auch die Medium-Elterngrößen von 232 Kindern aus der ersten Züricher Longitudinalgrößenstudie werden in einer Wechselbeziehungsanalyse erfaßt.

Ergebnisse: Die Verläufe der quadrierten Verhältnisse von Steh-, Sitzgröße beziehungsweise Beinlänge mit denen von Knochenaltern nach RUS-Methode (Radius [Speiche], Ulna [Elle], Short bones [kleine Knochen]) beziehungsweise Medium-Elterngröße werden präsentiert. Beide Datenmengen werden außerdem als Funktionen des Alters dargestellt.

Schlußfolgerungen: Während des Stadiums der Pubertät lassen sich Größenunterschiede bei bis zu 50% der Jungen und bis zu 40% der Mädchen mit den Schwankungen im reifungsbedingten Wachstumstempo erklären.

Resumen. Antecedentes: No es fácil disponer de información acerca del efecto que tiene la variabilidad en el ritmo madurativo sobre la variabilidad estatural alcanzada a la misma edad.

Objetivo: El estudio obtuvo esta información a partir de los datos del Primer Estudio Longitudinal de Zurich (First Zurich Longitudinal Study).

Sujetos y métodos: Se han incluido en un análisis de correlaciones las medidas anuales de la estatura, la talla sentado y la longitud de la pierna así como las estimaciones anuales de la edad ósea (RUS, TW3) y la estatura media de los progenitores, de 232 niños del Primer Estudio Longitudinal de Zurich (First Zurich Longitudinal Study).

Resultados: Se presentan las variaciones de las correlaciones cuadráticas de la estatura, la talla sentado y la longitud de la pierna con la edad ósea alcanzada basada en el mètodo RUS (radio, ulna y huesos cortos), la estatura media de los progenitores y ambas en función de la edad.

Conclusiones: Durante la pubertad, hasta el 50% de la variación estatural de los chicos y el 40% de la de las chicas se explica por el ritmo madurativo.     

Evaluation of the prognostic potential of EGFL7 in pilocytic astrocytomas

Pilocytic astrocytoma (PA) is the most frequent solid neoplasm in childhood. It has a good 5‐year overall survival (90% in childhood and 52% in adults). However, up to 20% of patients experience residual tumor growth, recurrence, and death. Although the main genetic alteration of PAs, including KIAA1549:BRAF fusion, involves chromosome 7q34, we previously found frequent loss in chr9q34.3 locus in a small subset of these tumors. Among the genes present in this locus, EGFL7 is related to poor prognosis in several tumor types. In this study, we aimed to assess EGFL7 expression through immunohistochemistry, and to evaluate its prognostic value in a series of 64 clinically and molecularly well‐characterized pilocytic astrocytomas. We found high expression of EGFL7 in 71.9% of patients. Low EGFL7 expression was associated with older patients, the mean age mainly older than 11 years (P = 0.027). EGFL7 expression was not associated with presence of KIAA1549:BRAF fusion, BRAF mutation, FGFR1 mutation, nor FGFR1 duplication. Moreover, high EGFL7 expression was associated with high FGFR1 (P = 0.037) and 5′‐deoxy‐5′‐methyltioadenosine phosphorylase (MTAP) (P = 0.005) expression, and with unfavorable outcome of patients (P = 0.047). Multivariate analysis revealed low EGFL7 expression related to older patients and high EGFL7 expression related to retained expression of MTAP. In addition, we found a borderline significance of unfavorable outcome and high EGFL7 expression. Finally, EGFL7 expression was not associated with overall or event‐free survival of PA patients. Our findings point to EGFL7 expression as a novel candidate prognostic marker in PA, which should be further investigated.     

The perception of shared medical decision making of expert and lay people: Effects of observing a movie clip depicting a medical consultation

Objective

To test for differences between experts and lay people in assessment of the degree to which a doctor engaged in a shared decision making (SDM) with a patient using the OPTION scale and a movie clip as stimulus material.

Methods

A segment of the movie ‘Wit’, depicting the communication of the diagnosis and the therapy proposed of a cancer, was shown to (a) university students with no knowledge about doctor–patient communication; (b) nurses working in medicine departments; (c) advanced medical students; (d) hospital physicians. The participants were asked to complete the OPTION scale which measures the extent to which physicians involve patients in medical decisions. An analysis of variance was used to compare OPTION scores across the four groups and to compare males and females.

Results

Being female [F_(1,190) = 11.9; p < .001] and being familiar with medical issues [F_(3,190) = 11.09; p < .001] were both significantly associated with a negative evaluations of the doctor's ability to involve the patient in the SDM.

Conclusion

Lay people and males (including male experts), are less demanding regarding SDM abilities.

Practice implications

A more systematic use of videos and the OPTION scale as validated outcome measure could be helpful educational strategy for the teaching of SDM.     

Comparative proteomics reveals essential mechanisms for osmotolerance in Gluconacetobacter diazotrophicus

Plant growth-promoting bacteria are a promising alternative to improve agricultural sustainability. Gluconacetobacter diazotrophicus is an osmotolerant bacterium able to colonize several plant species, including sugarcane, coffee, and rice. Despite its biotechnological potential, the mechanisms controlling such osmotolerance remain unclear. The present study investigated the key mechanisms of resistance to osmotic stress in G. diazotrophicus. The molecular pathways regulated by the stress were investigated by comparative proteomics, and proteins essential for resistance were identified by knock-out mutagenesis. Proteomics analysis led to identify regulatory pathways for osmotic adjustment, de novo saturated fatty acids biosynthesis, and uptake of nutrients. The mutagenesis analysis showed that the lack of AccC protein, an essential component of de novo fatty acid biosynthesis, severely affected G. diazotrophicus resistance to osmotic stress. Additionally, knock-out mutants for nutrients uptake (Δtbdr and ΔoprB) and compatible solutes synthesis (ΔmtlK and ΔotsA) became more sensitive to osmotic stress. Together, our results identified specific genes and mechanisms regulated by osmotic stress in an osmotolerant bacterium, shedding light on the essential role of cell envelope and extracytoplasmic proteins for osmotolerance.     

Omega-3 Fatty Acids Alter Systemic Inflammatory Mediators Caused by Apical Periodontitis

IntroductionThis study investigated the effects of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) on serum inflammatory mediators of rats with pulp exposure–induced apical periodontitis.MethodsForty male Wistar rats were divided into the following groups: control, untreated rats (C); control rats treated with ω-3 PUFAs (C-O); rats with pulp exposure–induced apical periodontitis (AP); and rats with pulp exposure–induced apical periodontitis treated with ω-3 PUFAs (AP-O). ω-3 PUFAs were administered orally once a day for 15 days before pulp exposure and continued for 30 days after pulp exposure. The rats were sacrificed, and then blood and jaw samples were collected. Blood analysis was conducted to determine the total number of leukocytes including neutrophils, monocytes, and lymphocytes. Proinflammatory cytokines tumor necrosis factor alpha, interleukin (IL) 6, and IL-17 were quantified by enzyme-linked immunosorbent assay. Histologic analysis was performed to confirm the development of apical periodontitis. The data were statistically evaluated using analysis of variance and the Tukey posttest. The significance level was set at 5%.ResultsThe development of apical periodontitis was confirmed in all infected groups. Bone destruction was larger in the AP group compared with the AP-O group (P < .05). Blood analysis showed that the AP and AP-O groups showed higher numbers of lymphocytes, leukocytes, monocytes, eosinophils, and expressions of tumor necrosis factor alpha and IL-6 compared with the C and C-O groups (P < .05). In contrast, the presence of leukocytes, lymphocytes, and the expression of IL-6 decreased in the AP-O group compared with the AP group (P < .05).Conclusionsω-3 PUFA supplementation influences the systemic effects caused by apical periodontitis, decreasing the number of leukocytes, lymphocytes, and IL-6 in rat blood.     

Maternal Apical Periodontitis Increases Insulin Resistance and Modulates the Antioxidant Defense System in the Gastrocnemius Muscle of Adult Offspring

IntroductionMaternal apical periodontitis (AP) is associated with insulin resistance (IR) in adult offspring. Oxidative stress has been linked to IR. This study investigated insulin sensitivity (IS) and oxidative stress in the gastrocnemius muscle (GM) of adult offspring of rats with AP.MethodsFifteen female Wistar rats were distributed into a control group, a group with 1 tooth with AP, and a group with 4 teeth with AP. Thirty days after AP induction, female rats were mated with healthy male rats. When male offspring reached 75 days of age, glycemia, insulinemia, and IS were determined. In the GM, the oxidative damage products (thiobarbituric acid reactive substances and carbonyl protein) and activities of enzymatic (superoxide dismutase, catalase, and glutathione peroxidase) and nonenzymatic (glutathione and total antioxidant capacity) antioxidants were quantified. Analysis of variance was performed followed by the Tukey post hoc test (P < .05).ResultsMaternal AP was associated with decreased IS and changes in antioxidant activities (reduced superoxide dismutase and increased catalase, glutathione peroxidase, and glutathione) and decreased thiobarbituric acid reactive substance concentration in the GM of their adult offspring. However, maternal AP does not appear to affect glycemia, carbonyl protein concentration, and the nonenzymatic total antioxidant capacity in the GM of this offspring.ConclusionsMaternal AP modulates the antioxidant defense system in the GM of their adult offspring, attenuating lipid peroxidation in this tissue. This reflects part of an adaptive response of the offspring to the stimulation of the maternal chronic oral inflammatory process in which the organism acts by decreasing oxidative tissue damage in the postnatal stage. The present study improves knowledge about the impact of maternal oral inflammation on healthy offspring.