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Despite a growing understanding of factors that drive monomer self-assembly to form supramolecular polymers, the effects of aromaticity gain have been largely ignored. Herein, we document the aromaticity gain in two different self-assembly modes of squaramide-based bolaamphiphiles. Importantly, O → S substitution in squaramide synthons resulted in supramolecular polymers with increased fiber flexibility and lower degrees of polymerization. Computations and spectroscopic experiments suggest that the oxo- and thiosquaramide bolaamphiphiles self-assemble into "head-to-tail"versus "stacked"arrangements, respectively. Computed energetic and magnetic criteria of aromaticity reveal that both modes of self-assembly increase the aromatic character of the squaramide synthons, giving rise to stronger intermolecular interactions in the resultant supramolecular polymer structures. These examples suggest that both hydrogen-bonding and stacking interactions can result in increased aromaticity upon self-assembly, highlighting its relevance in monomer design.

Background and Aims Fractures are a disabling clinical outcome after kidney transplantation (KTx), with incidence 5 to 34 times higher expected in males and females, respectively. Denosumab, a fully human monoclonal antibody that binds to RANKL with high affinity and specificity, blocking the interaction of RANKL with RANK, mimicking the endogenous effects of osteoprotegerina, increase bone mineral density; however, its effects to reduce the risk of vertebral fractures and ameliorate BMD remain undefinite in the KTx. Method Thirteen kidney recipients (aged from 50 to 79 yy, 6.2 + 5.5 (SD) yy after KTx), 6 M and 7 F (all postmenopausal) with nearly normal renal function (creat. 1.1+-0.31 mg/dl), affected by low energy vertebral fractures (21 dorsal and 1 lumbar vertebrae), evaluated by morphometric X-ray absorptiometry (Hologic DQR-4500A), were treated with denosumab (four 60-mg doses of denosumab Q6M) over 24 months. Data for vertebral heights and height ratios (P-A), covering 9 vertebral bodies were obtained, besides the data of vertebral, femural and radius BMD.The immunosuppressive regimen consisted of CNI (TAC or CsA), MMF and 8 out of 13 patients were still taking prednisone. Bone mineral metabolism parameters (whole-PTH, 25OHD3 and alcaline phosphatase) were also evaluated. Results No sides effects were observed, and all Patients concluded the study.After two years of denosumab treatment, we observed a significative reduction of vertebral T-score (from -2.12 +- 0.35 (SE) to -1.67+-0.35; p< .02), while T score of femural and radius did not show significative variation (-1.86+-0.21 versus -1.84+- 0.23 and -3.04+-0.42 versus -3.19+-0.45, respectively). The number of low energy vertebral fractures, basal versus two years control, had increased for only two dorsal vertebral fractures. However, to one of two subjects, with new dorsal vertebral fractures, was administered high dose of methylprednison for a severe kidney reject. No variations were observed in whole-PTH (89.31+-19.9 versus 68.38+-9.8 pg/ml), 25OHD3 (24.02+-2.75 versus 26.67+-2.29 ug/dl) and alcaline phosphatase (78.46+-12.73 versus 56.77+-7.14 UI). Conclusion Treatment with denosumab improve BMD at vertebral site in KTx, despite continuous steroid therapy and reduce the risk of new low energy vertebral fractures

The occurrence and extent of apoptosis in the kidneys of patients with diabetic nephropathy is largely unknown. We evaluated apoptosis in renal biopsies obtained from patients with early or advanced type II diabetic nephropathy. Apoptosis was about 6- and 3-fold higher, respectively, in glomeruli and tubules in kidneys of patients with early nephropathy than in the normal kidney and this was not further increased in advanced diabetic nephropathy. Glomerular apoptosis was related directly to hemoglobin A1 c and systolic blood pressure, whereas tubular cell apoptosis correlated to diabetes duration and low-density lipoprotein-cholesterol. Fas, Fas ligand, and p38 mitogen-activated protein kinase expressions were enhanced in glomeruli and tubules; however, this did not correlate with apoptosis. In patients with proteinuria, apoptosis was associated with the subsequent loss of kidney function. When these parameters were subjected to multivariate analysis, only glomerular apoptosis retained a significant independent predictive value. Our findings suggest that apoptosis might be a clinically relevant mechanism of glomerular and tubular cell loss in proteinuric type II diabetic patients.

We thank Drs Narisa and Prasit Futrakul for their interest in our paper.1 The findings observed in their studies, implying a maladaptive constriction of the efferent arteriole and downstream vascular and tubulointerstitial damage in type II diabetic patients, are appealing.2 One of the basic abnormalities in diabetic nephropathy is microalbuminuria, which eventually progresses to proteinuria. Downstream into the tubular compartment, the proteinuria induces a proinflammatory injury in tubular cells, which can ease the development of interstitial fibrosis and tubular atrophy.3 However, at variance with type I diabetic patients, a considerable number of type II diabetic patients, even with microalbuminuria or macroalbuminuria, have normal glomerular structure but show tubulointerstitial and/or arteriolar abnormalities.4 In type II diabetes, hyperglycemia5 and hypertension6 may cooperate to impair the physiologic mechanism that maintains normal glomerular capillary pressure and tubular function.6, 7