Challenges to Evidence Synthesis and Identification of Data Gaps in Human Biomonitoring.

The increasing number of human biomonitoring (HBM) studies undertaken in recent decades has brought to light the need to harmonise procedures along all phases of the study, including sampling, data collection and analytical methods to allow data comparability. The first steps towards harmonisation are the identification and collation of HBM methodological information of existing studies and data gaps. Systematic literature reviews and meta-analyses have been traditionally put at the top of the hierarchy of evidence, being increasingly applied to map available evidence on health risks linked to exposure to chemicals. However, these methods mainly capture peer-reviewed articles, failing to comprehensively identify other important, unpublished sources of information that are pivotal to gather a complete map of the produced evidence in the area of HBM. Within the framework of the European Human Biomonitoring Initiative (HBM4EU) initiative-a project that joins 30 countries, 29 from Europe plus Israel, the European Environment Agency and the European Commission-a comprehensive work of data triangulation has been made to identify existing HBM studies and data gaps across countries within the consortium. The use of documentary analysis together with an up-to-date platform to fulfil this need and its implications for research and practice are discussed.

"Diabetic nephropathy" in a non-diabetic patient.

Kimmelstiel and Wilson originally described nodular glomerulosclerosis as the pathognomonic lesion of diabetic nephropathy. Nevertheless, nodular glomerulosclerosis pattern can rarely occur in non-diabetic patients. In such cases, the differential diagnosis includes membranoproliferative glomerulonephritis, light or heavy chain deposition disease, amyloidosis, fibrillary and immunotactoid glomerulonephritis and chronic hypoxic or ischemic conditions. In cases that the above entities cannot be proven, the term idiopathic nodular glomerulosclerosis is given. Here, we report a case of a male patient with renal failure stage IV and non-nephrotic range proteinuria. He had a history of heavy smoking and hypertension. The kidney biopsy revealed diabetic-like lesions. However, there was no evidence of glucose impairment despite the thorough work-up at the biopsy time and thereafter. The laboratory data and the electron microscopy of the specimen could not prove any other cause of nodular glomerulosclerosis, and the final diagnosis was idiopathic nodular glomerulosclerosis. Moreover, we focus on the pathological differential diagnosis and work-up.

A common 'aggregation-prone' interface possibly participates in the self-assembly of human zona pellucida proteins.

Human zona pellucida (ZP) is composed of four glycoproteins, namely ZP1, ZP2, ZP3 and ZP4. ZP proteins form heterodimers, which are incorporated into filaments through a common bipartite polymerizing component, designated as the ZP domain. The latter is composed of two individually folded subdomains, named ZP-N and ZP-C. Here, we have synthesized six 'aggregation-prone' peptides, corresponding to a common interface of human ZP2, ZP3 and ZP4. Experimental results utilizing electron microscopy, X-ray diffraction, ATR FT-IR spectroscopy and polarizing microscopy indicate that these peptides self-assemble forming fibrils with distinct amyloid-like features. Finally, by performing detailed modeling and docking, we attempt to shed some light in the self-assembly mechanism of human ZP proteins.

Crescentic glomerulonephritis and membranous nephropathy: a rare coexistence.

BACKGROUND: The coexistence of crescents and membranous glomerulonephritis (MGN) is a special characteristic in lupus nephritis. In the absence of the characteristic histological features of lupus nephritis, MGN with crescents should raise the possibility of two other histopathological entities: anti-GBM disease and necrotizing and crescentic glomerulonephritis. The last one includes patients with positive ANCA serology or not. RESULTS AND CONCLUSIONS: Here, we describe a case of a male patient who presented with extrarenal vasculitis symptoms, acute renal failure, hematuria and nephrotic-range proteinuria. ANCA serology was positive, and the biopsy revealed crescentic vasculitis plus membranous nephropathy. Reviewing the whole literature about similar histological cases, we included 38 cases with ANCA-positive serology and 30 ones with no ANCA in serum. It seems that in the first category vasculitis symptoms predominate, while in the second one these symptoms are absent. Their histological features have no major differences. In any case, the clinical course of these patients is serious, and in most cases, immunosuppression is essential in order to avoid end-stage renal disease.

An N-terminal pro-atrial natriuretic peptide (NT-proANP) 'aggregation-prone' segment involved in isolated atrial amyloidosis.

Isolated atrial amyloidosis (IAA) is a common localized form of amyloid deposition within the atria of the aging heart. The main constituents of amyloid fibrils are atrial natriuretic peptide (ANP) and the N-terminal part of its precursor form (NT-proANP). An 'aggregation-prone' heptapeptide ((114)KLRALLT(120)) was located within the NT-proANP sequence. This peptide self-assembles into amyloid-like fibrils in vitro, as electron microscopy, X-ray fiber diffraction, ATR FT-IR spectroscopy and Congo red staining studies reveal. Consequently, remedies/drugs designed to inhibit the aggregation tendency of this 'aggregation-prone' segment of NT-proANP may assist in prevention/treatment of IAA, congestive heart failure (CHF) or atrial fibrillation (AF).