Staging of osteonecrosis of the jaw requires computed tomography for accurate definition of the extent of bony disease

Management of osteonecrosis of the jaw associated with antiresorptive agents is challenging, and outcomes are unpredictable. The severity of disease is the main guide to management, and can help to predict prognosis. Most available staging systems for osteonecrosis, including the widely-used American Association of Oral and Maxillofacial Surgeons (AAOMS) system, classify severity on the basis of clinical and radiographic findings. However, clinical inspection and radiography are limited in their ability to identify the extent of necrotic bone disease compared with computed tomography (CT). We have organised a large multicentre retrospective study (known as MISSION) to investigate the agreement between the AAOMS staging system and the extent of osteonecrosis of the jaw (focal compared with diffuse involvement of bone) as detected on CT. We studied 799 patients with detailed clinical phenotyping who had CT images taken. Features of diffuse bone disease were identified on CT within all AAOMS stages (20%, 8%, 48%, and 24% of patients in stages 0, 1, 2, and 3, respectively). Of the patients classified as stage 0, 110/192 (57%) had diffuse disease on CT, and about 1 in 3 with CT evidence of diffuse bone disease was misclassified by the AAOMS system as having stages 0 and 1 osteonecrosis. In addition, more than a third of patients with AAOMS stage 2 (142/405, 35%) had focal bone disease on CT. We conclude that the AAOMS staging system does not correctly identify the extent of bony disease in patients with osteonecrosis of the jaw.     

Impact of heterogeneity and socioeconomic factors on individual behavior in decentralized sharing ecosystems

Tens of millions of individuals around the world use decentralized content distribution systems, a fact of growing social, economic, and technological importance. These sharing systems are poorly understood because, unlike in other technosocial systems, it is difficult to gather large-scale data about user behavior. Here, we investigate user activity patterns and the socioeconomic factors that could explain the behavior. Our analysis reveals that (i) the ecosystem is heterogeneous at several levels: content types are heterogeneous, users specialize in a few content types, and countries are heterogeneous in user profiles; and (ii) there is a strong correlation between socioeconomic indicators of a country and users behavior. Our findings open a research area on the dynamics of decentralized sharing ecosystems and the socioeconomic factors affecting them, and may have implications for the design of algorithms and for policymaking.Every month, ∼150 million users worldwide share files over the Internet using BitTorrent (1), the most widely used decentralized peer-to-peer (P2P) communication protocol. Eleven years after its inception, file sharing through BitTorrent is one of the top three major contributors to the overall Internet traffic, accounting for 9–27% of the total traffic, depending on the continent (2, 3).The expansion in scale and breadth of decentralized file-sharing has highlighted the conflicts between the interests of creators (musicians and writers, e.g.) and those of P2P users. Creators and creative industries argue that they are being deprived of fair compensation for their work (4), which is being widely distributed for free in violation of copyright laws. Users, however, argue that P2P can be (and is) used for sharing nonproprietary contents, and warn that widespread monitoring of online activity by corporations and law enforcement violates P2P users’ right to privacy. Proof of the complexity of the situation includes the rejection of the Anti-Counterfeiting Trade Agreement by the European Parliament and the controversy with the Stop Online Piracy Act in the United States.Despite the growing social, economic, and technological importance of BitTorrent (4), there is currently little understanding of how users behave in this complex technosocial (5, 6) ecosystem. Due to the decentralized structure of P2P ecosystems, it is very difficult to gather large-scale data about interactions and behavioral patterns of the users without their explicit consent; this is in contrast to other forms of online exchange where all of the information is stored in a central system, be it publicly accessible as in Wikipedia (7), partially accessible through a public interface as in Twitter (8, 9) or Google [through its search logs (10) or its public services (11, 12)], or restricted as in Facebook (13, 14) or in email communications within organizations (15–18).Because of the difficulty to collect complete user-level data of large and representative samples of users (3), studies of user behavior in P2P networks have so far been based on (i) small datasets; (ii) aggregate data collected from “trackers” or from individual Internet service providers (ISPs); and (iii) incomplete user data collected using a single crawler client connected to the network (19–23).Here, we investigate the complete activity patterns of a large and representative pool of BitTorrent users. Our analysis reveals that P2P sharing is highly heterogeneous, that users are specialized, giving rise to well-defined user profiles, and that the abundance of certain user profiles in a country is highly correlated with socioeconomic factors. Our findings open a research area on the dynamics of decentralized sharing ecosystems, and may have implications for the understanding and design of algorithms and for policymaking.     

Phosphate homeostasis in Bartter syndrome: a case–control study

Background

Bartter patients may be hypercalciuric. Additional abnormalities in the metabolism of calcium, phosphate, and calciotropic hormones have occasionally been reported.

Methods

The metabolism of calcium, phosphate, and calciotropic hormones was investigated in 15 patients with Bartter syndrome and 15 healthy subjects.

Results

Compared to the controls, Bartter patients had significantly reduced plasma phosphate {mean [interquartile range]:1.29 [1.16–1.46] vs. 1.61 [1.54–1.67] mmol/L} and maximal tubular phosphate reabsorption (1.16 [1.00–1.35] vs. 1.41 [1.37–1.47] mmol/L) and significantly increased parathyroid hormone (PTH) level (6.1 [4.5–7.7] vs. 2.8 [2.2–4.4] pmol/L). However, patients and controls did not differ in blood calcium, 25-hydroxyvitamin D, alkaline phosphatase, and osteocalcin levels. In patients, an inverse correlation (P?P?P?Conclusions The results of this study demonstrate a tendency towards renal phosphate wasting and elevated circulating PTH levels in Bartter patients.     

Electrolyte abnormalities in cystic fibrosis: systematic review of the literature

Background

Cystic fibrosis per se can sometimes lead to hyponatremia, hypokalemia, hypochloremia or hyperbicarbonatemia. This tendency was first documented 60 years ago and has subsequently been confirmed in single case reports or small case series, most of which were retrospective. However, this issue has not been addressed analytically. We have therefore systematically reviewed and analyzed the available literature on this subject.

Methods

This was a systematic review of the literature.

Results

The reports included in this review cover 172 subacute and 90 chronic cases of electrolyte imbalances in patients with cystic fibrosis. The male:female ratio was 1.57. Electrolyte abnormalities were mostly associated with clinically inapparent fluid volume depletion, mainly affected patients aged ≤2.5 years, frequently tended to recur and often were found before the diagnosis of cystic fibrosis was established. Subacute presentation often included an history of heat exposure, vomiting, excessive sweating and pulmonary infection. History of chronic presentation, in contrast, was often inconspicuous. The tendency to hypochloremia, hypokalemia and metabolic alkalosis was similar between subacute and chronic patients, with hyponatremia being more pronounced (P?<?0.02) in subacute compared to chronic presentations. Subacute cases were treated parenterally; chronic ones were usually managed with oral salt supplementation. Retention of urea and creatinine was documented in 38 % of subacute cases.

Conclusions

The findings of our review suggest that physicians should be aware that electrolyte abnormalities can occur both as a presenting and a recurring feature of cystic fibrosis.     

Public clonotype usage identifies protective Gag-specific CD8+ T cell responses in SIV infection

Despite the pressing need for an AIDS vaccine, the determinants of protective immunity to HIV remain concealed within the complexity of adaptive immune responses. We dissected immunodominant virus-specific CD8⁺ T cell populations in Mamu-A*01⁺ rhesus macaques with primary SIV infection to elucidate the hallmarks of effective immunity at the level of individual constituent clonotypes, which were identified according to the expression of distinct T cell receptors (TCRs). The number of public clonotypes, defined as those that expressed identical TCR β-chain amino acid sequences and recurred in multiple individuals, contained within the acute phase CD8⁺ T cell population specific for the biologically constrained Gag CM9 (CTPYDINQM; residues 181–189) epitope correlated negatively with the virus load set point. This independent molecular signature of protection was confirmed in a prospective vaccine trial, in which clonotype engagement was governed by the nature of the antigen rather than the context of exposure and public clonotype usage was associated with enhanced recognition of epitope variants. Thus, the pattern of antigen-specific clonotype recruitment within a protective CD8⁺ T cell population is a prognostic indicator of vaccine efficacy and biological outcome in an AIDS virus infection.The global HIV pandemic demands an effective vaccine. However, while immunogenic vectors enter advanced clinical trials, the parameters on which to base measurements of efficacious immunity in a prospective manner remain unclear. Indeed, the recent Merck STEP trial failure has exposed our rudimentary understanding of protective determinants within the adaptive T cell response to HIV (1–3). It is established that specific CD8⁺ T cell immunity suppresses HIV replication in vivo and that certain patterns with respect to antigen targeting and MHC class I restriction are consistently associated with low levels of virus load (4–6). However, simple quantitative correlates, at least in peripheral blood, have proved elusive (7, 8). This paradox is exemplified by the SIV model, in which CD8⁺ T cell responses to the structurally constrained Gag CM9 epitope restricted by Mamu-A*01 are protective yet insufficient in terms of magnitude alone to define outcome (9, 10).In the absence of consistent numerical correlates of immune control, recent observational studies have focused on functional profiling in attempts to identify the properties that demarcate effective HIV-specific CD8⁺ T cell responses (11–15). Indeed, a broad consensus indicates that polyfunctionality within pathogen-specific T cell populations, which is related to the sensitivity of antigen recognition among other parameters, correlates with improved outcome measures (3, 16). However, the qualitative properties of CD8⁺ T cell populations are clearly affected by viral replication, and the extent to which such functional associates reflect deterministic attributes remains uncertain. Similarly, phenotypic analyses of HIV-specific CD8⁺ T cell populations have yet to provide definitive indicators of immune control (3). At a more fundamental level, a given cognate T cell response is defined by the nature of its constituent clonotypes, which are defined on the basis of their expressed TCRs and can be considered the elemental units of any antigen-specific T cell population. Thus, the primary interface between the virus and adaptive T cell immunity occurs at the level of TCR-mediated recognition of peptide-MHC antigen; these signal transduction events, in turn, dictate the ontogeny and biological characteristics of individual cognate T cells in vivo. Given the seminal importance of clonotype-dependent TCR-mediated recognition events, it is not unreasonable to propose that the potential efficacy of a composite virus-specific CD8⁺ T cell population might depend on the idiosyncrasies with which individual cognate TCRs engage the targeted viral antigen.In a previous study, we examined the clonotypic composition of immunodominant CD8⁺ T cell populations in acute SIV infection to illuminate the role of TCR usage in the process of mutational immune escape (17). In the present study, we conducted a detailed prospective study of vaccine-induced SIV-specific CD8⁺ T cell responses to the same immunodominant epitopes to establish whether the mobilized antigen-specific TCR repertoire can influence virologic outcome.     

Autoimmune diabetes not requiring insulin at diagnosis (latent autoimmune diabetes of the adult): definition, characterization, and potential prevention

Type 1 diabetes is caused by the immune-mediated destruction of islet insulin-secreting beta-cells. This chronic destructive process is associated with both cellular and humoral immune changes in the peripheral blood that can be detected months or even years before the onset of clinical diabetes. Throughout this prediabetic period, metabolic changes, including altered glucose tolerance and reduced insulin secretion, deteriorate at variable rates and eventually result in clinical diabetes. A fraction of individuals with humoral immunological changes have clinical diabetes that initially is not insulin-requiring. The onset of diabetes in these patients is usually in adult life, and because their diabetes is at least initially not insulin-requiring, they appear clinically to be affected by type 2 diabetes. Such patients probably have the same disease process as patients with type 1 diabetes in that they have similar HLA genetic susceptibility as well as autoantibodies to islet antigens, low insulin secretion, and a higher rate of progression to insulin dependency. These patients are defined as being affected by an autoimmune type of diabetes not requiring insulin at diagnosis, which is also named latent autoimmune diabetes of the adult (LADA). Special attention should be paid to diagnose such patients because therapy may influence the speed of progression toward insulin dependency, and in this respect, efforts should be made to protect residual C-peptide secretion. LADA can serve as a model for designing new strategies for prevention of type 1 diabetes but also as a target group for prevention in its own right.     

Brain tissue volume changes in relapsing-remitting multiple sclerosis: correlation with lesion load

The aim of this study was to simultaneously measure in vivo volumes of gray matter (GM), normal white matter (WM), abnormal white matter (aWM), and cerebro-spinal fluid (CSF), and to assess their relationship in 50 patients with relapsing-remitting multiple sclerosis (RR-MS) (age range, 21-59; mean EDSS, 2.5; mean disease duration, 9.9 years), using an unsupervised multiparametric segmentation procedure applied to brain MR studies. Tissue volumes were normalized to total intracranial volume providing corresponding fractional volumes (fGM, faWM, fWM, and fCSF), subsequently corrected for aWM-related segmentation inaccuracies and adjusted to mean patients' age according to age-related changes measured in 54 normal volunteers (NV) (age range 16-70). In MS patients aWM was 23.8 +/- 29.8 ml (range 0.4-138.8). A significant decrease in fGM was present in MS patients as compared to NV (49.5 +/- 3.2% vs 53.3 +/- 2.1%; P < 0.0001), with a corresponding increase in fCSF (13.0 +/- 3.8% vs 9.1 +/- 2.4%; P < 0.0001). No difference could be detected between the two groups for fWM (37.5 +/- 2.6% vs 37.6 +/- 2.2%). faWM correlated inversely with fGM (R = -0.434, P < 0.001 at regression analysis), and directly with fCSF (R = 0.473, P < 0.001), but not with fWM. There was a significant correlation between disease duration and EDSS, while no relationship was found between EDSS or disease duration and fractional volumes. Brain atrophy in RR-MS is mainly related to GM loss, which correlates with faWM. Both measures do not appear to significantly affect EDSS, which correlates to disease duration.     

Dinâmica ultrassonográfica dos volumes do conteúdo gástrico após a ingestão de água de coco ou sanduíche de carne. Um estudo cruzado controlado e randômico com voluntários saudáveis

Background

Adequate preoperative fasting is critical in preventing pulmonary aspiration of gastric content. We proposed to study the sonographic gastric content dynamics after the ingestion of liquid or solid food in healthy volunteers and confront it with current guidelines for preoperative fasting times.