Natural variation of the nef gene in human immunodeficiency virus type 2 infections in Portugal

Human immunodeficiency virus type 2 (HIV-2) infections cause severe immunodeficiency in humans, although HIV-2 is associated frequently with reduced virulence and pathogenicity compared to HIV-1. Genetic determinants that play a role in HIV pathogenesis are relatively poorly understood but nef has been implicated in inducing a more pathogenic phenotype in vivo. However, relatively little is known about the role of nef in HIV-2 pathogenesis. To address this, the genetic composition of 44 nef alleles from 37 HIV-2-infected individuals in Portugal, encompassing a wide spectrum of disease associations, CD4 counts and virus load, has been assessed. All nef alleles were subtype A, with no evidence of gross deletions, truncations or disruptions in the nef-encoding sequence; all were full-length and intact. HIV-2 long terminal repeat sequences were conserved and also indicated subtype A infections. Detailed analysis of motifs that mediate nef function in HIV-1 and simian immunodeficiency virus, such as CD4 downregulation and putative SH2/SH3 interactions, revealed significant natural variation. In particular, the central P(104)xxPLR motif exhibited wide interpatient variation, ranging from an HIV-1-like tetra-proline structure (PxxP)(3) to a disrupted minimal core motif (P(104)xxQLR). The P(107)-->Q substitution was associated with an asymptomatic phenotype (Fisher's exact test, P=0.026) and low virus loads. These data indicate that discrete differences in the nef gene sequence rather than gross structural changes are more likely to play a role in HIV-2 pathogenesis mediated via specific functional interactions

Recurrence and progression of periodontitis and methods of management in long-term care: A systematic review and meta-analysis

Aim: To systematically review the literature to evaluate the recurrence of disease of people in long-term supportive periodontal care (SPC), previously treated for periodontitis, and determine the effect of different methods of managing recurrence. The review focused on stage IV periodontitis. Materials and methods: An electronic search was conducted (until May 2020) for prospective clinical trials. Tooth loss was the primary outcome. Results: Twenty-four publications were retrieved to address recurrence of disease in long-term SPC. Eight studies were included in the meta-analyses for tooth loss, and three studies for disease progression/recurrence (clinical attachment level [CAL] loss ≥2 mm). For patients in SPC of 5–20 years, prevalence of losing more than one tooth was 9.6% (95% confidence interval [CI] 5%–14%), while experiencing more than one site of CAL loss ≥2 mm was 24.8% (95% CI 11%–38%). Six studies informed on the effect of different methods of managing recurrence, with no clear evidence of superiority between methods. No data was found specifically for stage IV periodontitis. Conclusions: A small proportion of patients with stage III/IV periodontitis will experience tooth loss in long-term SPC (tendency for greater prevalence with time). Regular SPC appears to be important for reduction of tooth loss. No superior method to manage disease recurrence was found

The Origin of Power-Law Emergent Scaling in Large Binary Networks

In this paper we study the macroscopic conduction properties of large but finite binary networks with conducting bonds. By taking a combination of a spectral and an averaging based approach we derive asymptotic formulae for the conduction in terms of the component proportions p and the total number of components N. These formulae correctly identify both the percolation limits and also the emergent power law behaviour between the percolation limits and show the interplay between the size of the network and the deviation of the proportion from the critical value of p = 1/2. The results compare excellently with a large number of numerical simulations

Investigating employee harassment via social media

Previously the investigation of employee harassment within the workplace would typically have involved obtaining evidence regarding physical contact, verbal contact (face to face or via telephone) or written contact (via letters or notes or email) between a suspect and a victim. Social media has added a new avenue to the investigation of employee harassment that goes beyond the physical workplace and normal working hours. In this paper we examine the process of computer forensic investigation of employee harassment via social media and the legal aspects of such. In particular we examine employee harassment via social media in terms of the reporting of harassment, the computer forensic investigation process, the relevant UK legislation and its application, and discuss good practice guidelines for educating employers and employees regarding how to use social media in the workplace and beyond in an acceptable manner

P109 The impact of tb nice guidance on resource capacity and contact screening outcomes: a retrospective, observational study within a central london tb centre

Introduction and objectives: Recently published NICE guidance has significantly expanded the approach to adult tuberculosis (TB) contact screening by recommending tuberculin skin testing (TST) for pulmonary and laryngeal contacts only, increasing the age threshold for screening and treatment to 65 years and defining a positive TST as induration ≥5 mm, regardless of BCG vaccination status. Interferon Gamma Release Assay (IGRA) is recommended only in situations where more evidence of infection is needed. Our institution has previously adopted an approach comprising a chest radiograph, TST and IGRA. The aim of our study was to evaluate the impact of NICE guidance on screening outcomes and resource capacity by applying the criteria to a well-defined historic cohort of TB contacts. Methods: This was a retrospective, observational study carried out at a central London teaching hospital. The study population comprised 593 consecutive, adult TB contacts screened between 1/1/2008 and 31/12/2010. Data was collected through a retrospective review of TST and IGRA tests. Results: Of the 593 contacts screened, 358 pulmonary contacts had TST and IGRA results. 56% had a TST ≥5 mm, regardless of BCG status, qualifying them for treatment as per the new NICE guidance. Of these, 61% were IGRA negative (discordant) and may therefore include false positive diagnoses, resulting in the potential for over treatment. In those with TST 5–14 mm, discordance rises to 84%. Conversely, 6% of those with TST < 5 mm are IGRA positive representing potentially missed cases. 16% of screened individuals were contacts of extra pulmonary TB. Not screening this group would reduce the demand for outpatient appointments by 151* in our cohort. In contrast, testing contacts > 35 years would require capacity for an additional 165* appointments. Furthermore, there were 162 additional LTBI cases in comparison to previous guidance requiring an additional 648* appointments. 72% of this group were IGRA negative. (*Approximate) Conclusions: Our results show the revised guidance will require increased resource capacity largely due to more patients being classified as having latent TB. In addition to workforce planning to meet these demands, further debate is needed to decide if this new approach truly reduces the incidence of active TB or results in unnecessary treatment

Diabetic Muscle Infarction: A Rare Complication of Long-Standing and Poorly Controlled Diabetes Mellitus

Objective. To report a case of diabetic muscle infarction (DMI), a rare complication of long-standing poorly controlled diabetes mellitus. Methods. We describe a case of a 45-year-old male with an approximately 8-year history of poorly controlled type 2 diabetes mellitus with multiple microvascular complications who presented with the sudden onset of left thigh pain and swelling. He had a swollen left thigh and a CK of 1670 U/L. He was initially treated with intravenous antibiotics for a presumptive diagnosis of pyomyositis or necrotizing fasciitis with no improvement. A diagnosis of diabetic muscle infarction was considered. Results. An MRI of the thigh demonstrated diffuse edema in the anterior compartment. A muscle biopsy demonstrated coagulation necrosis in skeletal muscle and inflammation and infarction in the walls of small blood vessels. These studies confirmed the final diagnosis of DMI. He was treated with supportive care and gradually improved. Conclusion. DMI is a rare complication of diabetes that is often mistaken for infections such as pyomyositis and necrotizing fasciitis or thrombophlebitis. Treatment is supportive. Although the short-term prognosis is good in these patients, the long-term prognosis is poor

Development of hepatic pathology in GBV‐B‐infected red‐bellied tamarins (Saguinus labiatus)

GB virus B (GBV‐B) is a new world monkey‐associated flavivirus used to model acute hepatitis C virus (HCV) infection. Critical for evaluation of antiviral or vaccine approaches is an understanding of the effect of HCV on the liver at different stages of infection. In the absence of longitudinal human tissue samples at defined time points, we have characterized changes in tamarins. As early as 2 weeks post‐infection histological changes were noticeable, and these were established in all animals by 6 weeks. Despite high levels of liver‐associated viral RNA, there was reversal of hepatic damage on clearance of peripheral virus though fibrosis was demonstrated in four tamarins. Notably, viral RNA burden in the liver dropped to near undetectable or background levels in all animals which underwent a second viral challenge, highlighting the efficacy of the immune response in removing foci of replication in the liver. These data add to the knowledge of GBV‐B infection in New World primates which can offer attractive systems for the testing of prophylactic and therapeutic treatments and the evaluation of their utility in preventing or reversing liver pathology