A classification method for neurogenic heterotopic ossification of the hip

Background: Existing classifications for heterotopic ossification (HO) do not include all HO types; nor do they consider the anatomy of the involved joint or the neurological injury. Therefore, we performed this study to propose and evaluate a classification according to the location of neurogenic HO and the neurological injury. Materials and methods: We studied the files of 24 patients/33 hips with brain or spinal cord injury and neurogenic HO of the hip treated with excision, indomethacin, and radiation therapy. We classified patients according to the Brooker classification scheme as well as ours. Four types of neurogenic HO were distinguished according to the anatomical location of HO: type 1, anterior; type 2, posterior; type 3, anteromedial; type 4, circumferential. Subtypes of each type were added based on the neurological injury: a, spinal cord; b, brain injury. Mean follow-up was 2.5 years (1-8 years). Results: The Brooker classification scheme was misleading - all hips were class III or IV, corresponding to ankylosis, even though only 14 hips had ankylosis. On the other hand, our classification was straightforward and easy to assign in all cases. It corresponded better to the location of the heterotopic bone, and allowed for preoperative planning of the appropriate surgical approach and evaluation of the prognosis; recurrence of neurogenic HO was significantly higher in patients with brain injury (subtype b), while blood loss was higher for patients with anteromedial (type 3) and circumferential (type 4) neurogenic HO. Conclusions: Our proposed classification may improve the management and evaluation of the prognosis for patients with neurogenic HO

The Prevalence and Drug Sensitivity of Tuberculosis among Patients Dying in Hospital in KwaZulu-Natal, South Africa: A Postmortem Study

A postmortem study by Ted Cohen and colleagues reveals a huge toll of tuberculosis among patients dying in hospitals in KwaZulu-Natal, South Africa

Paving (through) Amazonia: Neoliberal Urbanism and the Reperipheralization of Roraima

This paper examines the neoliberal reshaping of infrastructure provision in Brazil's extreme north since the mid-1990s, when roadway investments resulted in unprecedented regional connectivity. The BR-174 upgrade, the era's most important project, marked a transition from resource-based developmentalism to free-market transnationalism. Primarily concerned with urban competitiveness, the federal government funded the trunk roadway's paving to facilitate manufacturing exports from Manaus. While an effort was made to minimize deforestation, planners sidelined development implications in adjacent Roraima. The state's urban system has thus experienced reperipheralization and intensified primacy. Market-led growth now compounds the inheritance of hierarchical centralism and ongoing governmental neglect. Our study shows a vast territory dependent on primate cities for basic goods and services. Travelling with Roraimans from bypassed towns, we detected long-distance passenger transportation and surface logistics with selective routes. Heterogeneous Roraiman (im)mobilities comprise middle-class tourism and heightened consumerism as well as informal mobility tactics and transnational circulations of precarious labor. The paper exhorts neoliberal urbanism research to look beyond both Euro America's metropoles and their Global South counterparts. Urbanization dynamics in Brazil's extreme north demonstrate that market-disciplined investments to globalize cities produce far-reaching spatial effects. These are felt even by functionally-articulated-yet-marginalized peripheries in ostensibly remote locations

Metabolic Engineering of Cofactor F420 Production in Mycobacterium smegmatis

Cofactor F420 is a unique electron carrier in a number of microorganisms including Archaea and Mycobacteria. It has been shown that F420 has a direct and important role in archaeal energy metabolism whereas the role of F420 in mycobacterial metabolism has only begun to be uncovered in the last few years. It has been suggested that cofactor F420 has a role in the pathogenesis of M. tuberculosis, the causative agent of tuberculosis. In the absence of a commercial source for F420, M. smegmatis has previously been used to provide this cofactor for studies of the F420-dependent proteins from mycobacterial species. Three proteins have been shown to be involved in the F420 biosynthesis in Mycobacteria and three other proteins have been demonstrated to be involved in F420 metabolism. Here we report the over-expression of all of these proteins in M. smegmatis and testing of their importance for F420 production. The results indicate that co–expression of the F420 biosynthetic proteins can give rise to a much higher F420 production level. This was achieved by designing and preparing a new T7 promoter–based co-expression shuttle vector. A combination of co–expression of the F420 biosynthetic proteins and fine-tuning of the culture media has enabled us to achieve F420 production levels of up to 10 times higher compared with the wild type M. smegmatis strain. The high levels of the F420 produced in this study provide a suitable source of this cofactor for studies of F420-dependent proteins from other microorganisms and for possible biotechnological applications

Structural Characterization of CYP51 from Trypanosoma cruzi and Trypanosoma brucei Bound to the Antifungal Drugs Posaconazole and Fluconazole

Chagas Disease is caused by kinetoplastid protozoa Trypanosoma cruzi, whose sterols resemble those of fungi, in both composition and biosynthetic pathway. Azole inhibitors of sterol 14α-demethylase (CYP51), such as fluconazole, itraconazole, voriconazole, and posaconazole, successfully treat fungal infections in humans. Efforts have been made to translate anti-fungal azoles into a second-use application for Chagas Disease. Ravuconazole and posaconazole have been recently proposed as candidates for clinical trials with Chagas Disease patients. However, the widespread use of posaconazole for long-term treatment of chronic infections may be limited by hepatic and renal toxicity, a requirement for simultaneous intake of a fatty meal or nutritional supplement to enhance absorption, and cost. To aid our search for structurally and synthetically simple CYP51 inhibitors, we have determined the crystal structures of the CYP51 targets in T. cruzi and T. brucei, both bound to the anti-fungal drugs fluconazole or posaconazole. The structures provide a basis for a design of new drugs targeting Chagas Disease, and also make it possible to model the active site characteristics of the highly homologous Leishmania CYP51. This work provides a foundation for rational synthesis of new therapeutic agents targeting the three kinetoplastid parasites