Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Potential Contribution of Abnormal Talar Dome Lateral-Wall Geometry to Development of Ankle Osteoarthritis

Category: Ankle Arthritis Introduction/Purpose: Abnormal tibial plafond geometry, varus deformity and insufficient talar anterior coverage in particular, is well recognized as congenital factors predisposing ankles to osteoarthritis (OA), both primarily and after lateral ligament injury. Presumably, abnormal geometry of the gutter articulations (for the medial and lateral malleoli) also increases a risk of ankle OA, though this concept has not been well addressed to date. The talar side-wall surfaces, which appears to be less affected by degenerative deformity in ankle OA, may leave the congenital characteristics of the gutter articulation geometry. To identify a type of ankles at higher risk of OA development in this context, the present study explored characteristics of the talar side-wall geometry in OA ankles. Methods: Clinical CT images, from 21 moderate to advanced OA ankles without critical preceding pathologies and from 29 age- matched non-OA ankles, were subjected to 3-D morphometric evaluation of the talar dome side-wall geometry. Using a DICOM viewer (AquariusNET®, TeraRecon, Foster City, CA, USA), a local coordinate system for each ankle was manually established using talar landmarks. Then, on a transverse section at 3-5 mm distal to the superior aspect of the talar trochlea, the angle between the medial and lateral side-wall tangential lines (regressed from five cortical surface reference points for each) was measured as the “anterior opening angle.” Similarly, the “inferior opening angle” was measured on a mid-coronal section. Differences between groups were statistically tested using a t-test, with the significant level of p set at 0.05. Results: The anterior opening angle was significantly larger (p = 0.006) in the OA ankles (mean +/- SD: 11.9 +/- 6.0 degrees) than in the non-OA ankles (8.5 +/- 3.2). The inferior opening angle was also significantly larger (p = 0.007) in the OA ankles (30.7 +/- 11.1) than in the non-OA ankles (25.2 +/- 5.5). Defining the range of mean +/- 2SD as “normal” (Figure), 13 out of 21 (62%) OA ankles had both or either abnormally large anterior and/or inferior opening of the talar side-wall surfaces. Conclusion: Anterior and inferior opening trapezoidal shapes are common characteristic of the talar dome geometry. It is also well recognized that the degrees of opening substantially vary across individuals. The present study documented frequent occurrence of excessive anterior and/or inferior opening in OA ankles. Assuming that these abnormalities are inherent characteristics rather than results of degeneration, excessive anterior and inferior openings of the talar dome side-walls could be pathogenetical factors that increase a risk of ankle OA. Clinically, when ankles with excessive anterior and/or inferior opening talar dome side-walls would have ligament insufficiency, surgical repair or reconstruction should be considered to minimize a risk of future OA development

Abnormal Gutter Geometry as a Risk Factor of Chronic Ankle Instability

Category: Ankle, Sports Introduction/Purpose: Abnormalities in the tibial plafond geometry, such as varus deformity or insufficient talar anterior coverage, have been recognized as the congenital risk factors of chronic ankle instability (CAI) and eventual osteoarthritis (OA) development. Given that the gutter articulations are playing a substantial role in ankle stability, presumably, geometrical abnormality of these articulations also increases such risks, though this concept has not been well addressed to date. Our recent study (2016 AOFAS Annual Summer Meeting) revealed that OA ankles are frequently (>50%) marked by excessive anterior and/or inferior opening of the talar side-walls. The present study examined whether or not CAI cases share these geometrical characteristic, so as to identify a risk factor that predispose ankles to CAI and eventual OA development. Methods: Clinical multi-detector computed tomography (MDCT) images, from 29 symptomatic CAI cases who were indicated for surgical repair or reconstruction of the lateral ligaments, and from 54 asymptomatic non-degenerative (control) ankles, were selected for 3-D morphometric evaluation of the talar dome side-wall geometry. Using a DICOM viewer, a local coordinate system for each ankle was established using talar landmarks. Then, on a transverse section at 3-5 mm distal to the superior aspect of the talar trochlea, the angle between the medial and lateral side-wall tangential lines (regressed from five cortical surface reference points for each) was measured as the “anterior opening angle.” Similarly, the “inferior opening angle” was measured on a mid-coronal section. Differences between groups were statistically tested using a t-test. Results: The anterior opening angles in CAI cases (mean +/- SD: 11.9 +/- 4.4 degrees) were significantly larger (p < 0.001) than in control cases (7.4 +/- 3.4). Defining the range of mean +/- 2SD in Control as “normal” (Figure 1), 9 out of 29 CAI cases (31%) had excessive anterior opening of the talar side-wall surfaces. Although the inferior opening angle did not exhibit significant difference between the groups (28.5 +/- 9.6 in CAI versus 25.5 +/- 5.9 in Control, p = 0.082). Defining the range of mean +/- 2SD in Control as “normal” (Figure 1), 4 CAI cases (14%) had excessive inferior opening. In total, 12 out of 29 CAI cases (41%) had abnormal talar side-wall geometry. Conclusion: These data suggest that a certain fraction of CAI ankles feature abnormal geometrical characteristics consistent with OA ankles, i.e. excessive anterior and/or inferior opening of the talar dome side-walls. Given that none of the CAI cases had remarkable degenerative or traumatic deformities, these characteristics are arguably congenital. Theoretically, the posteriorly narrower shape of the talar trochlea would reduce talocurural congruity in plantar flexion, while the inferiorly wider shape itself would reduce coronal plane stability. These geometrical abnormalities appear to predispose ankles to CAI. For such ankles, aggressive surgical stabilization may forestall OA development following lateral ligament injuries

Chronic Encapsulated Expanding Thalamic Hematoma Associated with Obstructive Hydrocephalus following Radiosurgery for a Cerebral Arteriovenous Malformation: A Case Report and Literature Review

Chronic encapsulated intracerebral hematoma is a unique type of intracerebral hematoma accompanied by a capsule that is abundant in fragile microvasculature occasionally causing delayed regrowth. A 37-year-old man who had undergone radiosurgery for an arteriovenous malformation (AVM) causing intracerebral hematoma in the left parietal lobe presented with headache, vomiting, and progressive truncal ataxia due to a cystic lesion that had been noted in the left thalamus, leading to progressive obstructive hydrocephalus. He underwent left frontal craniotomy via a transsylvian fissure approach, and the serous hematoma was aspirated. The hematoma capsule was easy to drain and was partially removed. Pathological findings demonstrated angiomatous fibroblastic granulation tissue with extensive macrophage invasion. The concentration of vascular endothelial growth factor (VEGF) was high in the hematoma (12012 pg/mL). The etiology and pathogenesis of encapsulated hematoma are unclear, but the gross appearance and pathological findings are similar to those of chronic subdural hematoma. Based on the high concentration of VEGF in the hematoma, expansion of the encapsulated hematoma might have been caused by the promotion of vascular permeability of newly formed microvasculature in the capsule

Combined Unilateral Hemilaminectomy and Thoracoscopic Resection of the Dumbbell-Shaped Thoracic Neurinoma: A Case Report

A 41-year-old woman complained of chest pain when coughing. Computed tomography and magnetic resonance imaging disclosed a homogenously enhanced tumor occupying the spinal canal at the Th7 level and extending into the right paravertebral space through the intervertebral foramen between Th7 and Th8. The tumor was successfully removed via a posterolateral approach using unilateral hemilaminectomy followed by thoracoscopic surgery. Since the tumor had a dumbbell shape, a combined approach was considered essential. The histological diagnosis was a thoracic neurinoma. Combined hemilaminectomy and thoracoscopic surgery may be a good alternative for the management of thoracic dumbbell-shaped tumors