Epigenetic dysregulation of virulence gene expression in severe Plasmodium falciparum malaria

Chronic infections with the human malaria parasite Plasmodium falciparum depend on antigenic variation. P. falciparum erythrocyte membrane protein 1 (PfEMP1), the major erythrocyte surface antigen mediating parasite sequestration in the microvasculature, is encoded in parasites by a highly diverse family of var genes. Antigenic switching is mediated by clonal variation in var expression, and recent in vitro studies have demonstrated a role for epigenetic processes in var regulation. Expression of particular PfEMP1 variants may result in parasite enrichment in different tissues, a factor in the development of severe disease. Here, we study in vivo human infections and provide evidence that infection-induced stress responses in the host can modify PfEMP1 expression via the perturbation of epigenetic mechanisms. Our work suggests that severe disease may not be the direct result of an adaptive virulence strategy to maximize parasite survival but that it may indicate a loss of control of the carefully regulated process of antigenic switching that maintains chronic infections.     

Water treatment and handwashing behaviors among non-pregnant friends and relatives of participants in an antenatal hygiene promotion program in Malawi

Access to safe drinking water and improved hygiene are essential for preventing diarrheal diseases. To integrate hygiene improvement with antenatal care, free hygiene kits (water storage containers, water treatment solution, soap) and educational messages were distributed to pregnant women at antenatal clinics in Malawi. We assessed water treatment and hygiene practices of 275 non-pregnant friends and relatives of the hygiene kit recipients at baseline and follow-up nine months later to measure program impact on non-participants in the same communities. At follow-up, friends and relatives who did not receive kits or education were more likely than at baseline to purchase and use water treatment solution (25% versus 1%; P < 0.0001) and demonstrate correct handwashing practices (60% versus 18%; P < 0.0001). This antenatal clinic-based program resulted in improved water treatment and hygiene behaviors among non-pregnant friends and relatives living in the same communities as hygiene kit recipients, suggesting that program benefits extended beyond direct beneficiaries.     

Azacitidine augments expansion of regulatory T cells after allogeneic stem cell transplantation in patients with acute myeloid leukemia (AML)

Strategies that augment a GVL effect without increasing the risk of GVHD are required to improve the outcome after allogeneic stem cell transplantation (SCT). Azacitidine (AZA) up-regulates the expression of tumor Ags on leukemic blasts in vitro and expands the numbers of immunomodulatory T regulatory cells (Tregs) in animal models. Reasoning that AZA might selectively augment a GVL effect, we studied the immunologic sequelae of AZA administration after allogeneic SCT. Twenty-seven patients who had undergone a reduced intensity allogeneic transplantation for acute myeloid leukemia were treated with monthly courses of AZA, and CD8(+) T-cell responses to candidate tumor Ags and circulating Tregs were measured. AZA after transplantation was well tolerated, and its administration was associated with a low incidence of GVHD. Administration of AZA increased the number of Tregs within the first 3 months after transplantation compared with a control population (P = .0127). AZA administration also induced a cytotoxic CD8(+) T-cell response to several tumor Ags, including melanoma-associated Ag 1, B melanoma antigen 1, and Wilm tumor Ag 1. These data support the further examination of AZA after transplantation as a mechanism of augmenting a GVL effect without a concomitant increase in GVHD.     

Gastrointestinal mucormycosis—four cases with different risk factors, involving different anatomical sites

Mucormycosis of the gastrointestinal tract is a rare infection that usually occurs in patients who are immunocompromised and carries a high mortality. We report four cases of gastrointestinal mucormycosis seen over a one year period with different presentations, risk factors and different anatomical sites of involvement. A preoperative diagnosis was made only in one patient. All underwent surgery, three survived and one died postoperatively from multiorgan failure.     

Transitioning outcome measures: relationship between the CMTPedS and CMTNSv2 in children,adolescents, and young adults with Charcot‐Marie‐Tooth disease

Long‐term studies of Charcot‐Marie‐Tooth (CMT) disease across the entire lifespan require stable endpoints that measure the same underlying construct (e.g., disability). The aim of this study was to assess the relationship between the CMT Pediatric Scale (CMTPedS) and the adult CMT Neuropathy Score (CMTNSv2) in 203 children, adolescents, and young adults with CMT. There was a moderate curvilinear correlation between the CMTPedS and the CMTNSv2 (Spearman's rho ρ = 0.716, p < 0.0001), although there appears to be a floor effect of the CMTNSv2 in patients with a milder CMT phenotype. Univariate analyses indicate that the relationship between the CMTPedS and CMTNSv2 scores improves with worsening disease severity and advancing age. Although one universal scale throughout life would be ideal, our data supports the transition from the CMTPedS in childhood to the CMTNSv2 in adulthood as a continuum of measuring lifelong disability in patients with CMT.     

Is aggressive gap arthroplasty essential in the management of temporomandibular joint ankylosis?—a prospective clinical study of 15 cases

The purpose of this three-year, prospective, follow-up study was to evaluate whether aggressive gap arthroplasty is essential in the management of ankylosis of the temporomandibular joint (TMJ). Fifteen patients were treated by the creation of a minimal gap of 5–8 mm and insertion of an interpositional gap arthroplasty using the temporalis fascia. Eleven patients had unilateral coronoidectomy and 4 bilateral coronoidectomy based on Kaban's protocol. Preoperative assessment included recording of history, clinical and radiological examinations, personal variables, the aetiology of the ankylosis, the side affected, and any other relevant findings. Patients were assessed postoperatively by a surgeon unaware of the treatment given for a minimum of 3 years, which included measurement of the maximal incisal opening, presence of facial nerve paralysis, recurrence, and any other relevant findings. Of the 15 patients (17 joints), 12 had unilateral and three had bilateral involvement, with trauma being the most common cause. The patients were aged between 7 and 29 years (mean (SD) age 20 (8) years). Preoperative maximal incisal opening was 0–2 mm in 8 cases and 2–9 mm in 9. Postoperatively adequate mouth opening of 30–40 mm was achieved in all cases, with no recurrence or relevant malocclusion during 3-year follow up. However, patients will be followed up for 10 years. Aggressive gap arthroplasty is not essential in the management of ankylosis of the TMJ. Minimal gap interpositional arthroplasty with complete removal of the mediolateral ankylotic mass is a feasible and effective method of preventing recurrence.     

A Comparative Evaluation of the Linear Dimensional Accuracy of Four Impression Techniques using Polyether Impression Material

There is much discussion in the dental literature regarding the superiority of one impression technique over the other using addition silicone impression material. However, there is inadequate information available on the accuracy of different impression techniques using polyether. The purpose of this study was to assess the linear dimensional accuracy of four impression techniques using polyether on a laboratory model that simulates clinical practice. The impression material used was Impregum Soft?, 3 M ESPE and the four impression techniques used were (1) Monophase impression technique using medium body impression material. (2) One step double mix impression technique using heavy body and light body impression materials simultaneously. (3) Two step double mix impression technique using a cellophane spacer (heavy body material used as a preliminary impression to create a wash space with a cellophane spacer, followed by the use of light body material). (4) Matrix impression using a matrix of polyether occlusal registration material. The matrix is loaded with heavy body material followed by a pick-up impression in medium body material. For each technique, thirty impressions were made of a stainless steel master model that contained three complete crown abutment preparations, which were used as the positive control. Accuracy was assessed by measuring eight dimensions (mesiodistal, faciolingual and inter-abutment) on stone dies poured from impressions of the master model. A two-tailed t test was carried out to test the significance in difference of the distances between the master model and the stone models. One way analysis of variance (ANOVA) was used for multiple group comparison followed by the Bonferroni’s test for pair wise comparison. The accuracy was tested at α = 0.05. In general, polyether impression material produced stone dies that were smaller except for the dies produced from the one step double mix impression technique. The ANOVA revealed a highly significant difference for each dimension measured (except for the inter-abutment distance between the first and the second die) between any two groups of stone models obtained from the four impression techniques. Pair wise comparison for each measurement did not reveal any significant difference (except for the faciolingual distance of the third die) between the casts produced using the two step double mix impression technique and the matrix impression system. The two step double mix impression technique produced stone dies that showed the least dimensional variation. During fabrication of a cast restoration, laboratory procedures should not only compensate for the cement thickness, but also for the increase or decrease in die dimensions.