Capripoxvirus tissue tropism and shedding: A quantitative study in experimentally infected sheep and goats

Sheeppox virus and goatpox virus cause systemic disease in sheep and goats that is often associated with high morbidity and high mortality. To increase understanding of the pathogenesis of these diseases, we undertook quantitative time-course studies in sheep and goats following intradermal inoculation of Nigerian sheeppox virus or Indian goatpox virus in their respective homologous hosts. Viremia, determined by virus isolation and real-time PCR, cleared within 2 to 3 weeks post inoculation. Peak shedding of viral DNA and infectious virus in nasal, conjunctival and oral secretions occurred between 10 and 14 days post inoculation, and persisted at low levels for up to an additional 3 to 6 weeks. Although gross lesions developed in multiple organ systems, highest viral titers were detected in skin and in discrete sites within oronasal tissues and gastrointestinal tract. The temporal distribution of infectious virus and viral DNA in tissues suggests an underlying pathogenesis that is similar to smallpox and monkeypox where greatest viral replication occurs in the skin. Our data demonstrate that capripoxvirus infections in sheep and goats provide additional and convenient models which are suitable not only for evaluation of poxvirus-specific vaccine concepts and therapeutics, but also study of poxvirus-host interactions.     

One-on-one lifestyle coaching for managing adolescent obesity: Findings from a pilot, randomized controlled trial in a real-world, clinical setting

BACKGROUND:

Interventions for obese adolescents in real-world, clinical settings need to be evaluated because most weight management care occurs in this context.

OBJECTIVES:

To determine whether a lifestyle intervention that includes motivational interviewing and cognitive behavioural therapy (Health Initiatives Program [HIP]) leads to weight management that is superior to a similar lifestyle intervention (Youth Lifestyle Program [YLP]) that does not include these techniques; and to determine whether the HIP and YLP interventions are superior to a wait list control (WLC) group.

METHODS:

Obese adolescents were randomly assigned to a YLP (n=15), HIP (n=17) or WLC (n=14) group. The YLP and HIP were 16-session, one-on-one interventions. The primary outcome was the percentage change of body mass index z-score.

RESULTS:

Completers-only analyses revealed 3.9% (YLP) and 6.5% (HIP) decreases in the percentage change of body mass index z-score compared with a 0.8% (WLC) increase (P<0.001). Levels of attrition did not differ among groups, but were relatively high (approximately 20% to 40%).

CONCLUSION:

Lifestyle interventions delivered in a real-world, clinical setting led to short-term improvements in the obesity status of adolescents.     

Effects of pesticides on soil invertebrates in laboratory studies: a review and analysis using species sensitivity distributions

Species sensitivity distributions (SSD) and 5% hazardous concentrations (HC5) are distribution-based approaches for assessing environmental risks of pollutants. These methods have potential for application in pesticide risk assessments, but their applicability for assessing pesticide risks to soil invertebrate communities has not been evaluated. Using data obtained in a systematic review, the present study investigates the relevance of SSD and HC5 for predicting pesticide risks to soil invertebrates. Altogether, 1950 laboratory toxicity data were obtained, representing 250 pesticides and 67 invertebrate taxa. The majority (96%) of pesticides have toxicity data for fewer than five species. Based on a minimum of five species, the best available endpoint data (acute mortality median lethal concentration) enabled SSD and HC5 to be calculated for 11 pesticides (atrazine, carbendazim, chlorpyrifos, copper compounds, diazinon, dimethoate, gamma-hexachlorocyclohexane, lambda-cyhalothrin, parathion, pentachlorophenol, and propoxur). Arthropods and oligochaetes exhibit pronounced differences in their sensitivity to most of these pesticides. The standard test earthworm species, Eisenia fetida sensu lato, is the species that is least sensitive to insecticides based on acute mortality, whereas the standard Collembola test species, Folsomia candida, is among the most sensitive species for a broad range of toxic modes of action (biocide, fungicide, herbicide, and insecticide). These findings suggest that soil arthropods should be tested routinely in regulatory risk assessments. In addition, the data indicate that the uncertainty factor for earthworm acute mortality tests (i.e., 10) does not fully cover the range of earthworm species sensitivities and that acute mortality tests would not provide the most sensitive risk estimate for earthworms in the majority (95%) of cases.     

Implant Augmentation: Adding Bone Cement to Improve the Treatment of Osteoporotic Distal Femur Fractures: A Biomechanical Study Using Human Cadaver Bones

The increasing problems in the field of osteoporotic fracture fixation results in specialized implants as well as new operation methods, for example, implant augmentation with bone cement. The aim of this study was to determine the biomechanical impact of augmentation in the treatment of osteoporotic distal femur fractures.Seven pairs of osteoporotic fresh frozen distal femora were randomly assigned to either an augmented or nonaugmented group. In both groups, an Orthopaedic Trauma Association 33 A3 fractures was fixed using the locking compression plate distal femur and cannulated and perforated screws. In the augmented group, additionally, 1 mL of polymethylmethacrylate cement was injected through the screw. Prior to mechanical testing, bone mineral density (BMD) and local bone strength were determined. Mechanical testing was performed by cyclic axial loading (100 N to 750 N + 0.05N/cycle) using a servo-hydraulic testing machine.As a result, the BMD as well as the axial stiffness did not significantly differ between the groups. The number of cycles to failure was significantly higher in the augmented group with the BMD as a significant covariate.In conclusion, cement augmentation can significantly improve implant anchorage in plating of osteoporotic distal femur fractures.     

The role of transsphincteric pressure and proximal gastric volume in acid reflux before and after fundoplication

BACKGROUND & AIMS: This study was conducted to explore the role of proximal gastric volume and transsphincteric pressure on acid reflux during transient lower esophageal sphincter relaxation (TLESR) in patients with gastroesophageal reflux disease (GERD) both before and after laparoscopic fundoplication. METHODS: Twenty GERD patients were studied before and after fundoplication along with 20 healthy controls. High-resolution manometry and pH recording was performed for 1 hour before and 2 hours following meal ingestion (500 mL/300 kcal). Three-dimensional ultrasonographic images of the stomach were acquired before and every 15 minutes after meal ingestion. RESULTS: Postprandial proximal to total gastric volume distribution ratios were significantly larger in GERD patients before fundoplication (0.57 +/- 0.01; P < .05) and smaller following fundoplication (0.37 +/- 0.01; P < .001) compared with controls (0.46 +/- 0.01). The percentage of TLESRs associated with acid reflux did not relate to proximal gastric volume in any subject group. The transsphincteric pressure profile was different for TLESRs with and without reflux in GERD patients as well as in healthy controls. The pressure gradient across the esophagogastric junction (EGJ) (DeltaEGJp) was greater for TLESRs with acid reflux compared with TLESRs without acid reflux in both GERD patients (11.4 +/- 0.8 vs 8.0 +/- 0.5 mm Hg, respectively; P < .01) and controls (10.6 +/- 0.7 vs 7.1 +/- 0.8 mm Hg, respectively; P < .05). After fundoplication, DeltaEGJp during TLESRs was 7.9 +/- 0.9 mm Hg, and the transsphincteric pressure profile markedly changed. CONCLUSIONS: Although proximal gastric volume plays a key role in eliciting TLESRs, it is not related to the incidence of acid reflux during TLESRs. The transsphincteric pressure gradient is greater in TLESRs associated with acid gastroesophageal reflux.     

A pilot randomized trial comparing CD34-selected versus unmanipulated hemopoietic stem cell transplantation for severe,refractory rheumatoid arthritis

OBJECTIVE: Evidence from animal studies, case reports, and phase I studies suggests that hemopoietic stem cell transplantation (HSCT) can be effective in the treatment of rheumatoid arthritis (RA). It is unclear, however, if depletion of T cells in the stem cell product infused after high-dose chemotherapy is beneficial in prolonging responses by reducing the number of infused autoreactive T cells. This pilot multicenter, randomized trial was undertaken to obtain feasibility data on whether CD34 selection (as a form of T cell depletion) of an autologous stem cell graft is of benefit in the HSCT procedure in patients with severe, refractory RA. METHODS: Thirty-three patients with severe RA who had been treated unsuccessfully with methotrexate and at least 1 other disease-modifying agent were enrolled in the trial. The patients received high-dose immunosuppressive treatment with 200 mg/kg cyclophosphamide followed by an infusion of autologous stem cells that were CD34 selected or unmanipulated. Safety, efficacy (based on American College of Rheumatology [ACR] response criteria), and time to recurrence of disease were assessed on a monthly basis for up to 12 months. RESULTS: All patients were living at the end of the study, with no major unexpected toxicities. Overall, on an intent-to-treat basis, ACR 20% response (ACR20) was achieved in 70% of the patients. An ACR70 response was attained in 27.7% of the 18 patients who had received CD34-selected cells and 53.3% of the 15 who had received unmanipulated cells (P = 0.20). The median time to disease recurrence was 147 days in the CD34-selected cell group and 201 days in the unmanipulated cell group (P = 0.28). There was no relationship between CD4 lymphopenia and response, but 72% of rheumatoid factor (RF)-positive patients had an increase in RF titer prior to recurrence of disease. CONCLUSION: HSCT can be performed safely in patients with RA, and initial results indicate significant responses in patients with severe, treatment-resistant disease. Similar outcomes were observed in patients undergoing HSCT with unmanipulated cells and those receiving CD34-selected cells. Larger studies are needed to confirm these findings.     

Quantitative kinetic modelling and mapping of cerebral glucose transport and metabolism using glucoCESL MRI

Chemical-exchange spin-lock (CESL) MRI can map regional uptake and utilisation of glucose in the brain at high spatial resolution (i.e sub 0.2 mm³ voxels). We propose two quantitative kinetic models to describe glucose-induced changes in tissue R_1ρ and apply them to glucoCESL MRI data acquired in tumour-bearing and healthy rats. When assuming glucose transport is saturable, the maximal transport capacity (T_max) measured in normal tissue was 3.2 ± 0.6 µmol/min/mL, the half saturation constant (K_t) was 8.8 ± 2.2 mM, the metabolic rate of glucose consumption (MR_glc) was 0.21 ± 0.13 µmol/min/mL, and the cerebral blood volume (v_b) was 0.006 ± 0.005 mL/mL. Values in tumour were: T_max = 7.1 ± 2.7 µmol/min/mL, K_t = 14 ± 1.7 mM, MR_glc = 0.22 ± 0.09 µmol/min/mL, v_b = 0.030 ± 0.035 mL/mL. T_max and K_t were significantly higher in tumour tissue than normal tissue (p = 0.006 and p = 0.011, respectively). When assuming glucose uptake also occurs via free diffusion, the free diffusion rate (k_d) was 0.061 ± 0.017 mL/min/mL in normal tissue and 0.12 ± 0.042 mL/min/mL in tumour. These parameter estimates agree well with literature values obtained using other approaches (e.g. NMR spectroscopy).     

Recent Advances in Archaeological Science Techniques Special Feature: Dating the Paleolithic: Trapped charge methods and amino acid geochronology

Despite the vast array of different geochronological tools available, dating the Paleolithic remains one of the discipline’s greatest challenges. This review focuses on two different dating approaches: trapped charge and amino acid geochronology. While differing in their fundamental principles, both exploit time-dependent changes in signals found within crystals to generate a chronology for the material dated and hence, the associated deposits. Within each method, there is a diverse range of signals that can be analyzed, each covering different time ranges, applicable to different materials and suitable for different paleoenvironmental and archaeological contexts. This multiplicity of signals can at first sight appear confusing, but it is a fundamental strength of the techniques, allowing internal checks for consistency and providing more information than simply a chronology. For each technique, we present an overview of the basis for the time-dependent signals and the types of material that can be analyzed, with examples of their archaeological application, as well as their future potential.