Dengue Virus Envelope Dimer Epitope Monoclonal Antibodies Isolated from Dengue Patients Are Protective against Zika Virus.

UNLABELLED: Zika virus (ZIKV) is a mosquito-borne flavivirus responsible for thousands of cases of severe fetal malformations and neurological disease since its introduction to Brazil in 2013. Antibodies to flaviviruses can be protective, resulting in lifelong immunity to reinfection by homologous virus. However, cross-reactive antibodies can complicate flavivirus diagnostics and promote more severe disease, as noted after serial dengue virus (DENV) infections. The endemic circulation of DENV in South America and elsewhere raises concerns that preexisting flavivirus immunity may modulate ZIKV disease and transmission potential. Here, we report on the ability of human monoclonal antibodies and immune sera derived from dengue patients to neutralize contemporary epidemic ZIKV strains. We demonstrate that a class of human monoclonal antibodies isolated from DENV patients neutralizes ZIKV in cell culture and is protective in a lethal murine model. We also tested a large panel of convalescent-phase immune sera from humans exposed to primary and repeat DENV infection. Although ZIKV is most closely related to DENV compared to other human-pathogenic flaviviruses, most DENV immune sera (73%) failed to neutralize ZIKV, while others had low (50% effective concentration [EC50], <1:100 serum dilution; 18%) or moderate to high (EC50, >1:100 serum dilution; 9%) levels of cross-neutralizing antibodies. Our results establish that ZIKV and DENV share epitopes that are targeted by neutralizing, protective human antibodies. The availability of potently neutralizing human monoclonal antibodies provides an immunotherapeutic approach to control life-threatening ZIKV infection and also points to the possibility of repurposing DENV vaccines to induce cross-protective immunity to ZIKV. IMPORTANCE: ZIKV is an emerging arbovirus that has been associated with severe neurological birth defects and fetal loss in pregnant women and Guillain-Barré syndrome in adults. Currently, there is no vaccine or therapeutic for ZIKV. The identification of a class of antibodies (envelope dimer epitope 1 [EDE1]) that potently neutralizes ZIKV in addition to all four DENV serotypes points to a potential immunotherapeutic to combat ZIKV. This is especially salient given the precedent of antibody therapy to treat pregnant women infected with other viruses associated with microcephaly, such as cytomegalovirus and rubella virus. Furthermore, the identification of a functionally conserved epitope between ZIKV and DENV raises the possibility that a vaccine may be able to elicit neutralizing antibodies against both viruses.

Retrospective study of 476 tibial plateau levelling osteotomy procedures. Rate of subsequent 'pivot shift', meniscal tear and other complications.

OBJECTIVE: To determine the rate of subsequent 'pivot shift', meniscal tear and risk factors associated with complications of tibial plateau levelling osteotomy (TPLO) and to assess clinical and owner perception outcome. STUDY DESIGN: Retrospective study. SAMPLE POPULATION: Three hundred and forty-eight dogs that had undergone TPLO surgical procedures (n = 476 stifles). METHODS: Medical records were reviewed for the retrieval of information on breed, sex, age, body weight, clinical history, radiograph findings, pre- and postoperative tibial plateau angle, limb alignment, unilateral versus bilateral disease, condition of cranial cruciate ligament (CCL) and menisci, implant material, healing time and complications. Clinical and owner-assessed questionnaire outcomes were also recorded. RESULTS: Forty-six (9.7%) postoperative complications were reported. Twenty (4.2%) were classified as major complications requiring an additional surgical intervention, and 26 (5.5%) as minor complications. No risk factors associated with postoperative complications were identified. Ten (2.1%) subsequent meniscal injuries in the stifles with normal un- altered menisci at time of TPLO were reported with a median postoperative time of 9.5 months. Signs of postoperative 'pivot shift' were reported in 15 (3.1%) stifles. All stifles with a 'pivot shift' had a complete CCL rupture or a debrided partial CCL rupture; a medial menisectomy was identified as a risk factor for a 'pivot shift' (p = 0.02). Dogs with intact medial meniscus had a significantly higher activity level (p <0.0001) and a shorter time to peak function (p = 0.02) than dogs that underwent menisectomy according to an owner questionnaire. CONCLUSIONS: Dogs with TPLO and intact meniscus seemed to have a better and faster recovery than dogs with TPLO and menisectomy based on owner questionnaires. 'Pivot shift' was infrequent after TPLO surgery. All dogs with a 'pivot shift' had a complete CCL rupture or a debrided partial CCL rupture and menisectomy was identified as a risk factor for its occurrence. CLINICAL RELEVANCE: Considering the relatively low rate of subsequent meniscal injury after TPLO, systematic medial meniscal release with TPLO may be unnecessary. The 'pivot shift' deserved further investigation to completely understand its mechanism, to identify its anatomic components and potential consequences on the stifle joint.

Sci-Fri PM: Planning-12: Class II division interpretation of the amended Class II regulations.

The proposed amendments to the Class II regulations are expected to come into effect in May 2008. This presentation will provide highlights of the change to Class II regulations and how those changes will be interpreted by the CNSC during licence assessments and inspections. The changes to the regulations are designed to correct a number of regulatory deficiencies that have come to light since the regulations came into force.

Most obstructive sleep apnoea patients exhibit vigilance and attention deficits on an extended battery of tests.

Excessive daytime sleepiness, fatigue and altered attention are often experienced by obstructive sleep apnoea (OSA) patients. Although attentional problems are presumably responsible for part of the daytime functioning impairment in OSA, thorough investigation is unusual. Clinicians usually attribute these symptoms to somnolence. In clinical practice, only one isolated test is generally used to assess vigilance and attentional defects. It was hypothesised that most OSA patients exhibit a broad range of attentional deficits, beyond impaired maintenance of wakefulness, and a specific battery of tests is needed to correctly assess them. Three attentional tests were performed at 9:00, 11:00 and 13:30 h, measuring maintenance of wakefulness, sustained attention and divided attention. Twenty OSA patients (aged 51+/-12 yrs, apnoea/hypopnoea index 45+/-22 h) and 40 control subjects (aged 48.4+/-9.9 yrs) were tested. OSA patients performed significantly less well on the three tests than the controls at the three sessions. This battery of tests demonstrated that 95% of patients had vigilance and/or attentional impairment. Impairment patterns varied between patients. Vigilance is impaired in obstructive sleep apnoea patients over a wide range of attentional processes. Not only is their ability to remain awake in monotonous situations impaired but their ability to maintain attention in more stimulating conditions is also affected. A single test of vigilance is not sufficient and could underestimate impaired vigilance and attention in some patients.

Efectos cardiovascularesde la presión positiva continuaen la vía aérea en pacientes on insuficiencia cardíacay apnea del sueño / Cardiovascular effects of continuos positive airway pressure in patients with heart failure and obstructive sleep apnea

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Quality assessment of seven types of fresh-frozen plasma leucoreduced by specific plasma filtration.

BACKGROUND AND OBJECTIVES: A study was undertaken to determine plasma quality after specific filtration. MATERIALS AND METHODS: Seven types of plasma were tested, after filtration of plasma from filtered or non-filtered whole blood. Leucocyte counting was carried out after a 30-fold concentration of the sample. Twenty-nine parameters (including coagulation testing, proteins, coagulation factors and activation markers) were measured before and after filtration, and after 6 months of storage. RESULTS: After specific plasma filtration, the average residual leucocyte counts were less than 2250/l. In spite of small statistically significant changes in proteins, coagulation factors and complement activation, this study showed that plasma filtration did not alter plasma quality. After 6 months of storage at -30 degrees C, factor VIII recovery varied between 91 and 109%. Haemostasis parameters and activation markers remained within the normal range. CONCLUSIONS: Specific plasma filtration reduced the leucocyte number to < 104 leucocytes/l. The quality of plasma was not altered by the additional step of specific plasma filtration.

[Evaluation of nutrition instruction in a group of Senegalese students at the secondary level]. / Evaluation d'un enseignement sur la nutrition auprès d'élèves Sénégalais de niveau secondaire.

BACKGROUND: In Senegal, nutrition instruction was implanted in 1981 in the national curriculum of biology and has never been evaluated since. METHODS: The purpose of this study, was to evaluate the effect of a six weeks nutrition instruction program on improving nutrition knowledge and nutrition attitudes in an experimental group including 81 subjects aged 16.7+/-1.2 years and a control group including 80 subjects aged 15.7+/-1.3 years. These subjects came respectively from third and fourth grade. A questionnaire on knowledge and one on attitudes were administered to the experimental group, before and after the nutrition instruction, while the control group, who did not received any nutrition instruction, also answered the questionnaires. RESULTS: Results indicate that the adjusted mean knowledge posttest scores did not significantly increase in the experimental group compared to the control group. In addition, the adjusted mean attitude postscores of the boys and girls of the experimental group on the attitude scale "Nutrition affects health" were significantly higher from that of the control group. CONCLUSION: An evaluation of the nutrition curriculum and the teaching methods is suggested in order to improve the effectiveness of this nutrition program.

Comparison of ketoprofen, oxymorphone hydrochloride, and butorphanol in the treatment of postoperative pain in dogs.

OBJECTIVE: To compare analgesic effects of ketoprofen, oxymorphone hydrochloride, and butorphanol when used to control postoperative pain associated with elective orthopedic surgery in dogs. DESIGN: Prospective randomized clinical trial. ANIMALS: 70 dogs undergoing orthopedic surgery on a hind limb. PROCEDURE: Dogs were randomly assigned to 1 of 4 postoperative analgesic treatment groups: ketoprofen alone, oxymorphone alone, butorphanol alone, or ketoprofen-oxymorphone. Drugs were given IM at the end of anesthesia. Pain score, sedation score, arterial blood pressures, arterial blood gas partial pressures, and plasma cortisol concentration were measured for 12 hours after surgery. If the pain score was > or = 9, supplemental oxymorphone was administered IM. RESULTS: The proportion of dogs that did not require supplemental treatment with oxymorphone was significantly higher for the ketoprofen alone and ketoprofen-oxymorphone groups than for the oxymorphone alone group. During the first hour after surgery, pain score was lower for oxymorphone alone and ketoprofen-oxymorphone groups than for ketoprofen or butorphanol alone groups. Significant differences were not detected among groups in regard to pain score 2 and 3 hours after surgery or in regard to arterial blood pressures at any time. From 4 to 12 hours after surgery, pain score was significantly lower for the ketoprofen alone group than for other groups. Plasma cortisol concentration was significantly higher for the oxymorphone alone group 6 and 8 hours after surgery, compared with other groups. CLINICAL IMPLICATIONS: Except during the first hour after surgery, dogs given ketoprofen alone after elective orthopedic surgery had a greater level of, and longer-lasting, analgesia than did dogs given oxymorphone or butorphanol alone.

ADP-ribosylation of rye histones.

Chromatin from etiolated rye seedlings synthesized protein-bound, acid-insoluble material from [3H]NAD, presumably poly(ADP-ribose). [3H]ADP-ribosylated histone fractions were isolated from crude chromatin and characterized by gel electrophoresis and exclusion chromatography. It was found that histone H2B was the main acceptor, that H2A and H1 were modified to a lesser extent, and that H3 and H4 were only slightly modified. The average chain length on purified histones was 2.5 units of polymer.

[Preventive treatment of thromboembolic disease in thoracic surgery (author's transl)]. / Prévention de la maladie thrombo-embolique en chirurgie thoracique.

The aim of the present work is twofold: 1) to find a simple method of diagnosing a genuine risk of post operative thromboembolic disease: the level of platellets and of fibrine, the cephaline-kaolin test, the thromboelastogram and the para-coagulation tests were not considered satisfactory by authors. Only the isotopic detection of venous thrombosis is able to confirm the value of a given preventive treatment; 2) to achieve an effective prevemtive treatment: the pre and post-operative heparin therapy (an adaptation of Kakkar's method) eliminates the clinical accidents, reduces the number of isotopic venous thrombosis, but might increase the incidence of hemorrage.

[Prevention of thrombo-embolic accidents after pneumonectomy (author's transl)]. / Prévention des accidents thrombo-emboliques après pneumonectomie.

The authors analyzed the progress in the prevention of thrombo-embolic risk in 550 pneumonectomies divided chronologically in 4 groups : without anticoagulant treatment, with post-operative anti-vitamin K, with post-operative calcium heparinate, with pre and post-operative calcium heparinate. This study revealed the necessity of a pre-operative systematic preventive treatment : systematic, as there is no biological reason enabling the prevention of thrombosis risk. Pre-operative, because venous thrombosis and pulmonary embolism can occur very early.