The family of 14-3-3 proteins and specifically 14-3-3σ are up-regulated during the development of renal pathologies.

Chronic kidney disease, the end result of most renal and some systemic diseases, is a common condition where renal function is compromised due to fibrosis. During renal fibrosis, calreticulin, a multifunctional chaperone of the endoplasmic reticulum (ER) is up-regulated in tubular epithelial cells (TECs) both in vitro and in vivo. Proteomic analysis of cultured TECs overexpressing calreticulin led to the identification of the family of 14-3-3 proteins as key proteins overexpressed as well. Furthermore, an increased expression in the majority of 14-3-3 family members was observed in 3 different animal models of renal pathologies: the unilateral ureteric obstruction, the nephrotoxic serum administration and the ischaemia-reperfusion. In all these models, the 14-3-3σ isoform (also known as stratifin) was predominantly overexpressed. As in all these models ischaemia is a common denominator, we showed that the ischaemia-induced transcription factor HIF1α is specifically associated with the promoter region of the 14-3-3σ gene. Finally, we evaluated the expression of the family of 14-3-3 proteins and specifically 14-3-3σ in biopsies from IgA nephropathy and membranous nephropathy patients. These results propose an involvement of 14-3-3σ in renal pathology and provide evidence for the first time that hypoxia may be responsible for its altered expression.

Ki-67 Expression as a Factor Predicting Recurrence of Ductal Carcinoma In Situ of the Breast: A Systematic Review and Meta-Analysis.

BACKGROUND: Ki-67 is a marker of proliferating cells; in this meta-analysis we aimed to examine whether Ki-67 expression can predict recurrence rates of breast ductal carcinoma in situ (DCIS). MATERIALS AND METHODS: This systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eligible articles were sought in MEDLINE up to April 30, 2017. Random effects (DerSimonian-Laird) models were used for the calculation of pooled relative risk (RR) estimates; meta-regression analysis was also performed. Separate analyses were performed according to Ki-67 expression cutoff levels, invasiveness of recurrence, and adjustment of studies. RESULTS: Ten eligible cohort studies were synthesized; a significant association between Ki-67 expression and DCIS recurrence was noted for the Ki-67 cutoff at 10% (RR = 1.66; 95% confidence interval [CI], 1.14-2.42) as well as the Ki-67 cutoff at 14% (RR = 1.67; 95% CI, 1.01-2.77). Subanalysis on unadjusted (RR = 1.48; 95% CI, 1.06-2.07) and adjusted studies (RR = 2.19; 95% CI, 1.42-3.38) replicated the statistically significant findings. Ki-67 expression predicted the risk of invasive (RR = 1.53; 95% CI, 1.14-2.06) and noninvasive (RR = 1.59; 95% CI, 1.19-2.13) recurrence. CONCLUSION: This meta-analysis highlights Ki-67 expression as a predictor of DCIS recurrence; nevertheless, additional adjusted studies, with adequate follow-up periods, stemming from various world regions seem to be needed on this topic.

Ludovico Maria Barbieri (1662-1728), the unknown 17th century physician.

During the 17th century, Ludovico Maria Barbieri from Imola, Italy, discussed the requirement of a gas, seemingly oxygen, for living beings to function. On 6 December 1680, he published his only known work 'Spiritus nitro-aerei operations in microcosmo' in which he reviewed the function of oxygen and the apparatus he used based on the use of experiments rather than just theory. The scarcity of information about his life and work has resulted usually in him being a neglected figure in Italy. In this manuscript we uncover the extant information about his life and reveal that he had been a restless spirit and a great example to the 17th century scientific method.

Apollinaire Bouchardat (1806-1886): founder of modern Diabetology.

Apollinaire Bouchardat is regarded as the founder of the field of Diabetology. His contributions to the field include the first known recommendations for specific diets for the management of Diabetes Mellitus and his emphasis on patient education and self-monitoring. He was moreover a great pharmacist as well as a distinguished physician and biochemist.

Mary Mallon (1869-1938) and the history of typhoid fever.

Mary Mallon was born in 1869 in Ireland and emigrated to the US in 1884. She had worked in a variety of domestic positions for wealthy families prior to settling into her career as a cook. As a healthy carrier of Salmonella typhi her nickname of "Typhoid Mary" had become synonymous with the spread of disease, as many were infected due to her denial of being ill. She was forced into quarantine on two separate occasions on North Brother Island for a total of 26 years and died alone without friends, having evidently found consolation in her religion to which she gave her faith and loyalty.

Aretaeus of Cappodocia. Views on diphtheria.

Aretaeus of Cappadocia composed a vivid description of diphtheria, noting the symptoms, complications, as well as the remedies to cure it. He was the medical author who used the terms "eschara" and "diphtheres" which are still in use by modern physicians, and the first who recognized the croup. His alum remedy has stood the test of time and is nowadays still under study.

From the "hungry acid" to pepsinogen: a journey through time in quest for the stomach's secretion.

The stomach's secretion has been a mystery for centuries. Even after the first indications of its function and role appeared, every formulated idea on the nature of the gastric liquid remained open to controversy. After the ancient Greek perceptions which identified acids as bitter-sour liquids, the physicians of the Iatrochemical School, under the influence of Paracelsus and the alchemists, were the first to point out the physiologic chemistry of secretion. Experiments on animals and humans during the 17th-18th centuries, which mainly included swallowing various substances and observing the process, enhanced knowledge, with Stevens and Spallanzani playing the leading part. Any existing objections ceased in 1823, when Prout clearly identified hydrochloric acid as the acid agent of the stomach. Later on, the role of pepsin and pepsinogen was also judged to be important in digestion. In addition, the tremendous contribution of French scientists, experienced in the science of nutrition, must not be underestimated. It took centuries of research, and the involvement of many notable figures from many nations and countries, to form modern concepts of gastric secretion.