Stress-based performance evaluation of osseointegrated dental implants by finite-element simulation

In this paper biomechanical interaction between osseointegrated dental implants and bone is numerically investigated through 3D linearly elastic finite-element analyses, when static functional loads occur. Influence of some mechanical and geometrical parameters on bone stress distribution is highlighted and risk indicators relevant to critical overloading of bone are introduced. Insertions both in mandibular and maxillary molar segments are analyzed, taking into account different crestal bone loss configurations. Stress-based performances of five commercially-available dental implants are evaluated, demonstrating as the optimal choice of an endosseous implant is strongly affected by a number of shape parameters as well as by anatomy and mechanical properties of the site of placement. Moreover, effectiveness of some double-implant devices is addressed. The first one is relevant to a partially edentulous arch restoration, whereas other applications regard single-tooth restorations based on non-conventional endosteal mini-implants. Starting from computer tomography images and real devices, numerical models have been generated through a parametric algorithm based on a fully 3D approach. Furthermore, effectiveness and accuracy of finite-element simulations have been validated by means of a detailed convergence analysis

Hydrolysis of caprine and ovine milk proteins, brought about by aspartic peptidases from Silybum marianum flowers

The flowers of cardoon (Asteraceae) are a rich source of aspartic peptidases which possess milk clotting activity – and are thus used in traditional cheesemaking in the Iberian Peninsula. This study was aimed at characterizing the enzymatic action of the aspartic peptidases present in flowers of Silybum marianum (L.) Gaertn. (Asteraceae), specifically upon degradation of caseins. The proteolytic activities toward Na-caseinates previously prepared from caprine and ovine milks were studied, in a comparative fashion, using urea-PAGE, tricine-SDS-PAGE, densitometry, electroblotting and sequencing. Caprine as1- and b-caseins were degraded up to 68% and 40%, respectively, during 24 h of incubation. Only one important and well-defined band corresponding to a molecular weight of 14.4 kDa – i.e. a fragment of b-casein, was observed by 12 h of hydrolysis. By 24 h of incubation, ovine as- and b-caseins were degraded up to 76% and 19%, respectively. In what concerns specificity, the major cleavage site in ovine caseinate was Leu99-Arg100 in as1-casei

A CACNA1D mutation in a patient with persistent hyperinsulinaemic hypoglycaemia, heart defects, and severe hypotonia.

Congenital hyperinsulinaemic hypoglycaemia (HH) can occur in isolation or it may present as part of a wider syndrome. For approximately 40%-50% of individuals with this condition, sequence analysis of the known HH genes identifies a causative mutation. Identifying the underlying genetic aetiology in the remaining cases is important as a genetic diagnosis will inform on recurrence risk, may guide medical management and will provide valuable insights into β-cell physiology. We sequenced the exome of a child with persistent diazoxide-responsive HH, mild aortic insufficiency, severe hypotonia, and developmental delay as well as the unaffected parents. This analysis identified a de novo mutation, p.G403D, in the proband's CACNA1D gene. CACNA1D encodes the main L-type voltage-gated calcium channel in the pancreatic β-cell, a key component of the insulin secretion pathway. The p.G403D mutation had been reported previously as an activating mutation in an individual with primary hyper-aldosteronism, neuromuscular abnormalities, and transient hypoglycaemia. Sequence analysis of the CACNA1D gene in 60 further cases with HH did not identify a pathogenic mutation. Identification of an activating CACNA1D mutation in a second patient with congenital HH confirms the aetiological role of CACNA1D mutations in this disorder. A genetic diagnosis is important as treatment with a calcium channel blocker may be an option for the medical management of this patient

Nail-patella-like renal disease masquerading as Fabry disease on kidney biopsy: a case report

BACKGROUND: Genetic changes in the LIM homeobox transcription factor 1 beta (LMX1B) have been associated with focal segmental glomerulosclerosis (FSGS) without the extra-renal or ultrastructural manifestations of Nail-patella syndrome (NPS) known as Nail-patella-like renal disease (NPLRD). Fabry disease (FD) is an X-linked lysosomal disease caused by the deficiency of alpha-galactosidase A. The classic form of the disease is characterized by acroparesthesia, angiokeratomas, cornea verticillata, hypertrophic cardiomyopathy, strokes, and chronic kidney disease. Podocyte myelin bodies on ultrastructural examination of kidney tissue are very characteristic of FD; however some medications and other conditions may mimic this finding. CASE PRESENTATION: Here, we report on a female patient with chronic kidney disease (CKD), positive family history for kidney disease and kidney biopsy showing a FSGS lesion and presence of focal myelin figures within podocytes concerning for FD. However, genetic testing for FD was negative. After comprehensive clinical, biochemical, and genetic evaluation, including whole exome and RNA sequencing, she was ultimately diagnosed with NPLRD. CONCLUSIONS: This case illustrates the difficulties of diagnosing atypical forms of rare Mendelian kidney diseases and the role of a multidisciplinary team in an individualized medicine clinic setting in combination with state-of-the-art sequencing technologies to reach a definitive diagnosis

Diagnosis of Chikungunya Virus in Febrile Patients From a Malaria Holoendemic Area

Introduction: Accurate diagnosis of chikungunya (CHIK) is essential for effective disease management and surveillance. In a cohort of febrile Congolese patients, available diagnostic methods widely used in CHIK diagnosis were evaluated. In addition, plasma cytokines were quantified in CHIK patients and those coinfected with malaria compared with healthy controls. Methods: Between June and November 2019, a total of 107 febrile patients with suspected CHIK were subjected to differential diagnosis both for CHIK and malaria. Patients were screened for CHIK virus using molecular diagnosis by real-time PCR, serologic testing by IgM-specific and IgG-specific ELISAs, and lateral flow-based method with rapid diagnostic test (RDT), while malaria diagnosis was confirmed by PCR methods. Pro-inflammatory (IL-12, IL-16, IFN-γ, TNF-α) and anti-inflammatory (IL-4, IL-10, IL-13) cytokines were quantified in patients and healthy controls by ELISA assays. Results: Molecular diagnoses revealed that 57% (61/107) were positive for CHIK by RT-PCR, while serologic testing revealed 31% (33/107) and 9% (10/107) seropositivity for anti- IgM and IgG, respectively. None of the patients were CHIK RDT-positive. Also, 27% (29/107) were PCR-positive for malaria. Among the malaria-positive patients, 14% (15/107) were co-infected with CHIK and 13% (14/107) were monoinfection. Plasma IL-12 and TNF-α levels were increased in patients with malaria and IL-13 levels were increased in patients with co-infection (p<0.05). Conclusion: Co-infection of malaria and CHIK were common in febrile Congolese patients. Real-time PCR was a better tool for detecting actual occurrences of CHIK in a malaria holoendemic area