Toxoplasma gondii strains defective in oral transmission are also defective in developmental stage differentiation

Toxoplasma gondii undergoes differentiation from rapidly growing tachyzoites to slowly growing bradyzoites during its life cycle in the intermediate host, and conversion can be induced in vitro by stress. Representative strains of the three clonal lineages showed equal capacity to differentiate into bradyzoites in vitro, as evidenced by induction of bradyzoite antigen 1, staining with Dolichos biflorus lectin (DBL), pepsin resistance, and oral infectivity in mice. We also examined several recently described exotic strains of T. gondii, which are genetically diverse and have a different ancestry from the clonal lineages. The exotic strain COUG was essentially like the clonal lineages and showed a high capacity to induce bradyzoites in vitro and in vivo, consistent with its ability to be efficiently transmitted by the oral route. In contrast, exotic strains MAS and FOU, which are defective in oral transmission, showed a decreased potential to develop into bradyzoites in vitro. This defect was evident from reduced staining with DBL and the cyst antigen CST1, failure to down-regulate tachyzoite antigens, such as tachyzoite surface antigens 1 and 2A, and decreased resistance to pepsin treatment. Despite normal in vitro differentiation, the exotic strains CAST and GPHT also showed decreased oral transmission, due to formation of smaller cysts and a lower tissue burden during chronic infection, traits also shared by MAS and FOU. Collectively, these findings reveal that the limited oral transmission in some strains of T. gondii is due to inefficient differentiation to the bradyzoite form, leading to defects in the formation of tissue cysts.     

IPH4102, a monoclonal antibody directed against the immune receptor molecule KIR3DL2, for the treatment of cutaneous T-cell lymphoma

Introduction: Therapeutic options for mycosis fungoides and Sézary syndrome include a variety of immunomodulatory, epigenetic, and cytotoxic options; however, none has been demonstrated to be efficacious for all patients, or to deliver deep and durable responses to the majority of patients. In this review, we examine the monoclonal antibody, IPH4102, a novel agent for the treatment of cutaneous T-cell lymphoma.

Areas covered: In this review, we examine data demonstrating the tissue specificity of KIR3DL2 receptor, which is highly expressed on the malignant cells in cutaneous T-cell lymphoma, including mycosis fungoides and Sézary syndrome. This specificity has led to the development of the agent IPH4102. Preclinical data showing efficacy of IPH4102 in vivo are outlined, as well as the results from Phase I clinical trials, which suggest that the agent is both efficacious and well-tolerated. Larger scale clinical trials are to follow.

Expert Opinion: We examine the putative benefit of IPH4102 in comparison to established agents already in the clinic, highlighting its efficacy and relative safety. We also examine possible directions that may better define the role of IPH4102 in the treatment of T-cell lymphoma in the future.     

Public health dentistry pioneer: Alfred Kantorowicz in exile from Nazi rule

This paper discusses a dimly-lit and largely unknown time in the life of a great pediatric and public health dentistry pioneer. Alfred Kantorowicz survived extermination thanks to the fact that in 1933, Turkey began to reform its higher education using invitees fleeing the Nazis and for whom America was out of reach because of restrictive immigration laws and widespread anti-Semitic hiring policies at its universities. Kantorowicz introduced public health dentistry to Turkey years before it was practiced in the United States.     

Physician and nurse satisfaction with an Electronic Medical Record system

Electronic Medical Records (EMRs) are intended to support clinical activity, improve efficiency, and reduce error. Reluctance to use EMRs may exist among clinicians. The purpose of this study was to assess physician and nurse satisfaction with an Emergency Department (ED) EMR. We surveyed Emergency Medicine (EM) physicians and nurses at a large urban teaching hospital after implementation of an Emergency Department EMR. The questionnaire assessed: 1) computer background and experience; 2) perceptions regarding EMR use; and 3) concerns about impact upon quality of patient care. The clinicians find the EMR easy to use and are generally satisfied with the impact on their work. However, they report that the EMR has no positive impact on patient care. They report confusion in following the sequence of screens, and are concerned with the amount of time it takes to use the EMR and the confidentiality of patient information. Similar results were found between physicians and nurses. Nurses, but not physicians, report that they are able to finish work much faster than before implementation (p < 0.05). We were unable to correlate computer background and experience with satisfaction with an EMR. This survey suggests that EM physicians and nurses favor the use of an EMR and suggests opportunities for EMR enhancement.     

Role of sphingosine-1-phosphate phosphohydrolase 1 in the regulation of resistance artery tone

Sphingosine-1-phosphate (S1P), which mediates pleiotropic actions within the vascular system, is a prominent regulator of microvascular tone. By virtue of its S1P-degrading function, we hypothesized that S1P-phosphohydrolase 1 (SPP1) is an important regulator of tone in resistance arteries. Hamster gracilis muscle resistance arteries express mRNA encoding SPP1. Overexpression of SPP1 (via transfection of a SPP1(wt)) reduced resting tone, Ca2+ sensitivity, and myogenic vasoconstriction, whereas reduced SPP1 expression (antisense oligonucleotides) yielded the opposite effects. Expression of a phosphatase-dead mutant of SPP1 (SPP1(H208A)) had no effect on any parameter tested, suggesting that catalytic activity of SPP1 is critical. The enhanced myogenic tone that follows overexpression of S1P-generating enzyme sphingosine kinase 1 (Sk1(wt)) was functionally antagonized by coexpression with SPP1(wt) but not SPP1(H208A). SPP1 modulated vasoconstriction in response to 1 to 100 nmol/L exogenous S1P, a concentration range that was characterized as S1P2-dependent, based on the effect of S1P(2) inhibition by antisense oligonucleotides and 1 mumol/L JTE013. Inhibition of the cystic fibrosis transmembrane regulator (CFTR) (1) restored S1P responses that were attenuated by SPP1(wt) overexpression; (2) enhanced myogenic vasoconstriction; but (3) had no effect on noradrenaline responses. We conclude that SPP1 is an endogenous regulator of resistance artery tone that functionally antagonizes the vascular effects of both Sk1(wt) and S1P2 receptor activation. SPP1 accesses extracellular S1P pools in a manner dependent on a functional CFTR transport protein. Our study assigns important roles to both SPP1 and CFTR in the physiological regulation of vascular tone, which influences both tissue perfusion and systemic blood pressure.     

Transjugular liver biopsy: histological diagnosis success comparing the trucut to the modified aspiration Ross needle

BACKGROUND: Transjugular liver biopsy is an alternative procedure for patients who present contraindications to standard percutaneous procedure. AIM: To compare the rate of histological diagnosis obtained on transjugular liver biopsy with an automated trucut needle and with a modified Ross needle. PATIENTS / METHOD: Eighty-five patients with suspicion of chronic liver diseases and presenting contraindications for percutaneous liver biopsy (coagulopathy, massive ascites, morbid obesity, or chronic renal problems) were submitted to 89 transjugular liver biopsies between March 1994 and April 2001 at "Hospital S?o José, Irmandade da Santa Casa de Misercórdia", Porto Alegre, RS, Brazil. Thirty-five patients underwent 36 biopsies with an automated trucut needle, and 50 patients underwent 53 biopsies with a modified Ross needle. RESULTS: Histological diagnosis was reached in 32/35 subjects submitted to transjugular liver biopsy with the trucut needle (91%) and in 35/50 (70%) submitted to biopsy with the modified Ross needle. Specimens obtained with the trucut needle were significantly larger and less fragmented than those obtained with the Ross needle. CONCLUSION: Transjugular liver biopsy with the automated trucut needle allowed a higher rate of histological diagnosis when compared to the modified Ross needle in patients with suspicion of chronic liver diseases.     

Six-year follow-up of a point-source exposure to CWD contaminated venison in an Upstate New York community: risk behaviours and health outcomes 2005–2011

Objectives

It is currently unknown whether chronic wasting disease (CWD), a transmissible spongiform encephalopathy of cervids, is transmissible to humans. Reported on here are the behavioural risk factors and health conditions associated with a six-year follow-up of a known point-source exposure to a CWD infected deer in an Upstate New York community.

Study design

Longitudinal.

Methods

The Oneida County Chronic Wasting Disease Surveillance Project was launched in 2005 in response to a point-source exposure to a CWD infected deer at a March 2005 Sportsmen's feast in Upstate New York. Eighty-one exposed individuals participated in the 2005 baseline data collection, and were sent follow-up questionnaires following each deer hunting season between 2005 and 2011.

Results

Over a six year period, participants reported a reduction in overall venison consumption. Participants reported no significant changes in health conditions, although several conditions (vision loss, heart disease, type 2 diabetes, weight changes, hypertension, and arthritis), were significantly associated with age.

Conclusions

To this day, this incident remains the only known large-scale point-source exposure to a CWD infected deer. Prion diseases can incubate for multiple decades before the manifestation of clinical symptoms; thus, continued surveillance of this exposed study population represents a unique opportunity to assess the risk of CWD transmission to humans. This project is uniquely situated to provide the first epidemiological evidence of CWD transmission to humans, should it occur.     

Cognitive Therapy for Suicide Prevention: A Randomized Pilot with Suicidal Youth Experiencing Homelessness

Homeless youth have extremely high rates of suicidal ideation and attempts, but limited research has evaluated the efficacy of suicide prevention interventions. Suicidal homeless youth (N?=?150) between the ages of 18 to 24 years were recruited from a local drop-in center. Of interest was (1) whether the proposed sample of eligible youth could be identified, (2) whether youth could be engaged and retained in the prevention intervention, and (3) whether the intervention was associated with reduced suicidal ideation, our primary outcome measure. In particular, youth were randomly assigned to Cognitive Therapy for Suicide Prevention (CTSP)?+?Treatment as Usual (TAU) (N?=?75) or TAU alone (N?=?75). Findings showed that the proposed sample of eligible youth could be identified and engaged in the study, and all youth showed a significant decline in suicidal ideation over time, with a faster decline among youth assigned to CTSP. These findings suggest that (1) at-risk suicidal youth can be identified and engaged outside of hospital emergency rooms, such as in drop-in centers, and (2) intervention added to TAU can strengthen reductions in suicidal ideation. Ultimately, attention towards reducing suicide risk among these youth has the potential to reduce premature mortality, hospitalization and loss of human capital.