Pioneers in neurology: Leonardo da Vinci (1452–1519)

Journal of Neurology -     

Bone Mass,Bone Microstructure and Biomechanics in Patients with Hand Osteoarthritis

The impact of primary hand osteoarthritis (HOA) on bone mass, microstructure, and biomechanics in the affected skeletal regions is largely unknown. HOA patients and healthy controls (HCs) underwent high-resolution peripheral quantitative computed tomography (HR-pQCT). We measured total, trabecular, and cortical volumetric bone mineral densities (vBMDs), microstructural attributes, and performed micro–finite element analysis for bone strength. Failure load and scaled multivariate outcome matrices from distal radius and second metacarpal (MCP2) head measurements were analyzed using multiple linear regression adjusting for age, sex, and functional status and reported as adjusted Z-score differences for total and direct effects. A total of 105 subjects were included (76 HC: 46 women, 30 men; 29 HOA: 23 women, six men). After adjustment, HOA was associated with significant changes in the multivariate outcome matrix from the MCP2 head (p < .001) (explained by an increase in cortical vBMD (Δz = 1.07, p = .02) and reduction in the trabecular vBMD (Δz = −0.07, p = .09). Distal radius analysis did not show an overall effect of HOA; however, there was a gender-study group interaction (p = .044) explained by reduced trabecular vBMD in males (Δz = −1.23, p = .02). HOA was associated with lower failure load (−514 N; 95%CI, −1018 to −9; p = 0.05) apparent in males after adjustment for functional status. HOA is associated with reduced trabecular and increased cortical vBMD in the MCP2 head and a reduction in radial trabecular vBMD and bone strength in males. Further investigations of gender-specific changes of bone architecture in HOA are warranted. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.     

Decreased expression of inhibitory SMAD6 and SMAD7 in keloid scarring.

Keloids are benign skin tumours occurring during wound healing in genetically predisposed patients. They are characterised by an abnormal deposition of extracellular matrix components, in particular collagen. There is evidence that transforming growth factor-beta (TGFbeta) is involved in keloid formation. SMAD proteins play a crucial role in TGFbeta signaling and in terminating the TGFbeta signal by a negative feedback loop through SMAD6 and 7. It is unclear how TGFbeta signaling is connected to the pathogenesis of keloids. Therefore, we investigated the expression of SMAD mRNA and proteins in keloids, in normal skin and in normal scars. Dermal fibroblasts were obtained from punch-biopsies of keloids, normal scars and normal skin. Cells were stimulated with TGFbeta1 and the expression of SMAD2, 3, 4, 6 and 7 mRNA was analysed by real time RT-PCR. Protein expression was determined by Western blot analysis. Our data demonstrate a decreased mRNA expression of the inhibitory SMAD6 and 7 in keloid fibroblasts as compared to normal scar (p<0.01) and normal skin fibroblasts (p<0.05). SMAD3 mRNA was found to be lower in keloids (p<0.01) and in normal scar fibroblasts (p<0.001) compared to normal skin fibroblasts. Our data showed for the first time a decreased expression of the inhibitory SMAD6 and SMAD7 in keloid fibroblasts. This could explain why TGFbeta signaling is not terminated in keloids leading to overexpression of extracellularmatrix in keloids. These data support a possible role of SMAD6 and 7 in the pathogenesis of keloids.     

Description of site-specific morphology of keloid phenotypes in an Afrocaribbean population.

By examining the keloid scars of 211 Afrocaribbean patients presenting to the Plastic Surgery unit in Kingston, Jamaica, we have described site-specific morphologies of scarring; keloid disease is not a homogenous biological entity. All cases conformed to clinical criteria for diagnosis of keloid scarring: 369 keloid scars were present in 137 females (2-83 years; mean 29.6 years; SD+/-14.9 years) and 74 males (5-90 years, mean 29.5 years; SD+/-15.0 years). Morphologies were specific to each anatomical site: trunk scars (n=45,12.1%) were geometrically shaped with clear margins or irregular in outline, surface and margin; back single scars were well-demarcated botryoid but multiple scars were butterfly-shaped, spheroidal and irregular; chest scars (n=72,20.1%) were butterfly or nonbutterfly shaped found most commonly in the midsternal line; upper limb scars (n=57,15.3%) mostly in the deltoid region (propeller shaped) or elsewhere nodular, linear to irregular; ear (n=85,23%) commonest site being the lobe, having reniform to bulbous shape; face and neck (n=60,16.2%) scars were firm nodular to hard; posterior auricular scars were either horizontal and oblong-shaped or vertical and reniform in outline; scalp scars (n=11,2.8%) were commonest in the occipital area varying from small papules to large plaques; lower limb scars (n=39,10.5%) varied from propeller, butterfly, petalloid to dum-bell-shaped. Three plantar and eight pubic keloids were rare findings. Recognition of different morphological phenotypes is necessary in understanding genotypic predisposition and aiding diagnosis, treatment and prognosis of keloid scars.     

Autotransplantation of splenic tissue in an isolated segment of small intestine.

The ability of splenic tissue to regenerate when implanted in an isolated segment of small intestine with intact circulation was studied in six pigs. After total splenectomy, 10 per cent of the weight of the spleen was implanted in a 10-15-cm long isolated segment of small intestine with an intact vascular supply. Bowel continuity was established by end-to-end anastomosis. Before implantation, the mucosal layer was completely removed from the isolated segment of the small intestine. The animals were killed 6 months later and the isolated segment of small bowel containing the splenic tissue identified. Most of the implanted splenic tissue was recovered in the isolated segment of small intestine; the weight ranged from 43 to 120 (mean 80) per cent of that of the implanted tissue. An isolated segment of small intestine with an intact circulation produces a higher index of regeneration than other previously reported sites.     

Rhabdomyomatous mesenchymal hamartoma presenting on a digit

Rhabdomyomatous mesenchymal hamartoma is a rare dermal lesion comprised of skeletal muscle, adipocytes and collagen. The vast majority has been described in very young patients on the head and neck. To our knowledge, there are only two reports of rhabdomyomatous mesenchymal hamartoma outside the head and neck region. Both of those lesions were located in the perianal area. We describe a rhabdomyomatous mesenchymal hamartoma in a 36-year-old man located on the great toe. Although rhabdomyomatous mesenchymal hamartoma is uncommon, it is important to be aware of this entity, its possible association with congenital syndromes and its potential for localization outside of the head and neck region.     

MiRNA-Mediated Knock-Down of Bcl-2 and Mcl-1 Increases Fludarabine-Sensitivity in CLL-CII Cells

Background: Over-expression of anti-apoptotic proteins such as Bcl-2 and Mcl-1 is associated with resistance to chemotherapeutic agents such as fludarabine. Moreover, an inverse relationship between miRNA-15a levels with Bcl-2 and Mcl-1 expression has been observed in CLL patients. In this study, the effect of miRNA-15a on apoptosis and sensitivity of the CLL cells to fludarabine was investigated. Methods: After treatments, the Mcl-1 and Bcl-2 expression levels were quantified by RT-qPCR. Trypan blue assay was used to explore the effects of miRNA-15a and fludarabine on cell proliferation. The cytotoxicity was measured using MTT assay and combination index analysis. Cell death was determined using cell death detection ELISA assay and caspase-3 activity assay Kits. Results: Results showed that miRNA-15a clearly decreased the mRNA levels of Bcl-2 and Mcl-1 in a time dependent manner, which led to CLL-II cell proliferation inhibition and enhancement of apoptosis (p < 0.05, relative to control). Transfection of the miRNA-15a synergistically reduced the cell survival rate and lowered the IC50 value of fludarabine. Furthermore, miRNA-15a significantly enhanced the apoptotic effect of fludarabine. Conclusions: Our data propose that suppression of Bcl-2 and Mcl-1 by miRNA-15a can effectively inhibit the cell proliferation and sensitize CLL cells to fludarabine. Therefore, miRNA-15a can be considered as a potential therapeutic target in CLL resistant patients.