Malignant peripheral nerve sheath tumour: an elusive diagnosis.

Malignant peripheral nerve sheath tumour (MPNST) also termed as spindle cell malignancy of the peripheral nerve Schwann cells or neurogenic sarcoma, represents approximately 10% of all soft tissue sarcomas. This tumour is usually found in the lower extremities and only 10-12% of all lesions occur in the head and neck region, which makes it a rare entity. The diagnosis of MPNST has been described as one of the most difficult and elusive diagnosis in the soft tissue diseases because of its non-specific presentation both clinically and histopathologically. This was overcome by the use of immunohistochemistry. A case of MPNST of the left maxillary antrum in a 45 -year -old male patient is reported.     

Dysregulation of IGF-1/GLP-1 signaling in the progression of ALS: potential target activators and influences on neurological dysfunctions

Neurological Sciences - The prominent causes for motor neuron diseases like ALS are demyelination, immune dysregulation, and neuroinflammation. Numerous research studies indicate that the...     

Avidin as a model for charge driven transport into cartilage and drug delivery for treating early stage post-traumatic osteoarthritis

Local drug delivery into cartilage remains a challenge due to its dense extracellular matrix of negatively charged proteoglycans enmeshed within a collagen fibril network. The high negative fixed charge density of cartilage offers the unique opportunity to utilize electrostatic interactions to augment transport, binding and retention of drug carriers. With the goal of developing particle-based drug delivery mechanisms for treating post-traumatic osteoarthritis, our objectives were, first, to determine the size range of a variety of solutes that could penetrate and diffuse through normal cartilage and enzymatically treated cartilage to mimic early stages of OA, and second, to investigate the effects of electrostatic interactions on particle partitioning, uptake and binding within cartilage using the highly positively charged protein, Avidin, as a model. Results showed that solutes having a hydrodynamic diameter ≤10 nm can penetrate into the full thickness of cartilage explants while larger sized solutes were trapped in the tissue's superficial zone. Avidin had a 400-fold higher uptake than its neutral same-sized counterpart, NeutrAvidin, and >90% of the absorbed Avidin remained within cartilage explants for at least 15 days. We report reversible, weak binding (K_D ∼ 150 μm) of Avidin to intratissue sites in cartilage. The large effective binding site density (N_T ∼ 2920 μm) within cartilage matrix facilitates Avidin's retention, making its structure suitable for particle based drug delivery into cartilage.     

A survey of the career-defining determinants of prospective UK oral and maxillofacial surgical trainees

Increasing numbers of medics are applying to dental school to pursue a career in oral and maxillofacial surgery (OMFS), particularly in the aftermath of Modernising Medical Careers (MMC), but their perspectives, experience, and training up to this point differ widely. We aimed to characterise these differences in the light of MMC and beyond by doing a survey of 20 dentists and 24 medics who were applying for their second degree. They were questioned about factors that influenced their choice of career and university, the motivation to pursue specialty training, and were asked for their opinions on suggested measures for workforce planning. The medics were subdivided into those who had trained before MMC (n = 18), and those who had not (n = 6). Dentists had considerably more OMFS experience than medics (mean 22 months compared with 4.2 months), and 46% (11/24) of medics had no substantive OMFS experience. Of those who had trained before MMC 3/18 considered OMFS as their first choice of career, compared with 4/6 who have trained since, and 15/20 of dentists. Eighty-three percent (20/24) of medics admitted that MMC had influenced their choice of career, and 54% (13/24) had applied for training in a specialty other than OMFS, notably otolaryngology. The most favoured method of workforce planning among all respondents (25/44) was “roughly matching” places on a second degree to projected OMFS training posts.     

Development and organization of the human brain tissue compartments across the lifespan using diffusion tensor imaging

We used a diffusion tensor imaging-based whole-brain tissue segmentation to characterize age-related changes in (a) whole-brain grey matter, white matter, and cerebrospinal fluid relative to intracranial volume and (b) the corresponding brain tissue microstructure using measures of diffusion tensor anisotropy and mean diffusivity. The sample, a healthy cohort of 119 right-handed males and females aged 7-68 years. Our results demonstrate that white matter and grey matter volumes and their corresponding diffusion tensor anisotropy and mean diffusivity follow nonlinear trajectories with advancing age. In contrast, cerebrospinal fluid volume increases linearly with age.     

Neonatal testicular torsion with an unusual sonographic feature

Neonatal testicular torsion is a rare entity, the exact etiology of which is not elucidated. Imaging is performed using color Doppler ultrasound and scintigraphic studies with typically diminished testicular flow on the side with torsion. We present a case of testicular torsion in a newborn with increased testicular vascularity demonstrated by ultrasound and suggesting a torsion-detorsion sequence. Management of patients with torsion involves assessing the risks of neonatal surgery versus the possibility of finding viable testicular tissue at surgical exploration.     

TSHR is the main causative locus in autosomal recessively inherited thyroid dysgenesis

Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder and results in mental retardation if untreated. Eighty-five percent of CH cases are due to disruptions in thyroid organogenesis and are mostly sporadic, but about 2% of thyroid dysgenesis is familial, indicating the involvement of genetic factors in the aetiology of the disease. In this study, we aimed to investigate the Mendelian (single-gene) causes of non-syndromic and non-goitrous congenital hypothyroidism (CHNG) in consanguineous or multi-case families. Here we report the results of the second part (n=105) of our large cohort (n=244), representing the largest such cohort in the literature, and interpret the overall results of the whole cohort. Additionally, 50 sporadic cases with thyroid dysgenesis and 400 unaffected control subjects were included in the study. In familial cases, first, we performed potential linkage analysis of four known genes causing CHNG (TSHR, PAX8, TSHB, and NKX2-5) using microsatellite markers and then examined the presence of mutations in these genes by direct sequencing. In addition, in silico analyses of the predicted structural effects of TSHR mutations were performed and related to the mutation specific disease phenotype. We detected eight new TSHR mutations and a PAX8 mutation but no mutations in TSHB and NKX2-5. None of the biallelic TSHR mutations detected in familial cases were present in the cohort of 50 sporadic cases. Genotype/phenotype relationships were established between TSHR mutations and resulting clinical presentations. Here we conclude that TSHR mutations are the main detectable cause of autosomal recessively inherited thyroid dysgenesis. We also outline a new genetic testing strategy for the investigation of suspected autosomal recessive non-goitrous CH.