The immunodeficient scid mouse as a model for human lymphatic filariasis

The C.B.-17-scid/scid mouse (hereafter referred to as the scid mouse) is homozygous for a recessive mutation at a locus that influences the assembly of intact immunoglobulin and T cell receptor genes. Therefore, scid mice cannot generate functional B or T lymphocytes, are profoundly immunodeficient, and have been reported to be receptive to reconstitution with human immune cells. In the present study, we injected scid mice with infective larvae of the human filarial parasite Brugia malayi. Within 6-10 wk after subcutaneous injection of infective L3 larvae, both male and female worms were observed in various stages of development in 90% of the mice. In animals tested 8 weeks or more after infection, microfilariae were detected in the blood or peritoneal cavity of 52% of the mice examined. Adult worms were observed in the lymphatics of the infected scid mice, where their presence was associated with lymphangitis and lymphangiectasia. These results suggest that the scid mouse model of lymphatic filariasis may be important in investigation of the interaction of the murine, and possibly the human, immune system with the lymphatic filarial parasite.     

Recapitulation of normal and abnormal BB rat immune system development in scid mouse/rat lymphohemopoietic chimeras.

Mice homozygous for the mutation "severe combined immune deficiency" (C.B17-scid/scid) lack functional T and B lymphocytes and readily accept tumor xenografts. Partial lymphohemopoietic scid/human and mouse/rat chimeras have been described, but complete chimerization with thymic engraftment and generation of donor-origin thymocytes has not been achieved. We now report that low-dose irradiation permits the engraftment of BB rat fetal liver stem cells in scid recipients. We observed that BB rat fetal liver cells injected into irradiated scid mice establish a rat hemopoietic system in the scid mouse bone marrow and populate the scid mouse thymus. These stem cells generated rat-origin thymocytes that migrated to the scid mouse spleen, a peripheral lymphoid organ. Finally, we found that xenogeneic chimeras created using fetal liver cells from the abnormal (lymphopenic, diabetes prone) subline of BB rats recapitulated both the quantitative and phenotypic abnormalities of the donor rat. Xenogeneic lymphohemopoietic chimeras established in scid mice may provide a powerful new tool in the study of immune system development and autoimmunity.     

B1 B lymphocytes play a critical role in host protection against lymphatic filarial parasites

Host defense against multicellular, extracellular pathogens such as nematode parasites is believed to be mediated largely, if not exclusively, by T lymphocytes. During our investigations into the course of Brugia malayi and Brugia pahangi infections in immunodeficient mouse models, we found that mice lacking B lymphocytes were permissive for Brugian infections, whereas immunocompetent mice were uniformly resistant. Mice bearing the Btk(xid) mutation were as permissive as those lacking all B cells, suggesting that the B1 subset may be responsible for host protection. Reconstitution of immunodeficient recombination activating gene (Rag)-1(-/)- mice with B1 B cells conferred resistance, even in the absence of conventional B2 lymphocytes and most T cells. These results suggest that B1 B cells are necessary to mediate host resistance to Brugian infection. Our data are consistent with a model wherein early resistance to B. malayi is mediated by humoral immune response, with a significant attrition of the incoming infectious larval load. Sterile clearance of the remaining parasite burden appears to require cell-mediated immunity. These data raise the possibility that the identification of molecule(s) recognized by humoral immune mechanisms might help generate prophylactic vaccines.     

The Role of Fear-Related Behaviors in the 2013–2016 West Africa Ebola Virus Disease Outbreak

The 2013–2016 West Africa Ebola virus disease pandemic was the largest, longest, deadliest, and most geographically expansive outbreak in the 40-year interval since Ebola was first identified. Fear-related behaviors played an important role in shaping the outbreak. Fear-related behaviors are defined as “individual or collective behaviors and actions initiated in response to fear reactions that are triggered by a perceived threat or actual exposure to a potentially traumatizing event. FRBs modify the future risk of harm.” This review examines how fear-related behaviors were implicated in (1) accelerating the spread of Ebola, (2) impeding the utilization of life-saving Ebola treatment, (3) curtailing the availability of medical services for treatable conditions, (4) increasing the risks for new-onset psychological distress and psychiatric disorders, and (5) amplifying the downstream cascades of social problems. Fear-related behaviors are identified for each of these outcomes. Particularly notable are behaviors such as treating Ebola patients in home or private clinic settings, the “laying of hands” on Ebola-infected individuals to perform faith-based healing, observing hands-on funeral and burial customs, foregoing available life-saving treatment, and stigmatizing Ebola survivors and health professionals. Future directions include modeling the onset, operation, and perpetuation of fear-related behaviors and devising strategies to redirect behavioral responses to mass threats in a manner that reduces risks and promotes resilience.     

Combined open and endovascular repair of acute type A aortic dissection

In 3 patients previously undergoing one and one-half ventricular repair, right ventricular dysfunction progressed for more than 10 years. Their clinical features resembled those seen in patients undergoing the atriopulmonary Fontan procedure, and reoperation was carried out for conversion to total cavopulmonary connection. Hemodynamics improved subsequent to the circulatory renewal. In 2 patients having atrial arrhythmia before conversion, the resected right atrial wall illustrated grossly abnormal histopathology. These patients suffered from persistent sinus nodal dysfunction and eventually needed pacemaker implantation. The third patient died of sepsis 4 months later.     

Evaluation of real time polymerase chain reaction assays for confirmation of Neisseria gonorrhoeae in clinical samples tested positive in the Roche Cobas Amplicor assay

OBJECTIVE: Development of a rapid, sensitive, and accurate assay for confirmation of Neisseria gonorrhoeae in clinical samples. METHOD: Two real time polymerase chain reaction (PCR) assays, developed on the LightCycler for amplification of the N gonorrhoeae cppB gene, were utilised for confirmation of this bacterial pathogen in samples positive by the Roche Cobas Amplicor assay. Performance characteristics of the two assays were compared with other commercial nucleic acid amplification assays, including the Abbott LCx and Roche 16S rRNA tests. RESULTS: All related Neisseria as well as other bacterial species tested negative by both cppB gene based assays, whereas 120 N gonorrhoeae clinical isolates from various geographical regions gave in positive results. Both assays had a sensitivity of one copy per reaction. 122 clinical samples positive and another 50 samples negative for N gonorrhoeae by Roche Cobas Amplicor were selected from a specimen pool of more than 3000 women tested previously. Overall, 73 of 122 (59.8%) samples were confirmed as positive. The two real time assays had sensitivities of 99% and 100% and specificities of 98% and 100%, respectively. The 16S and LCx assays produced similar results to the real time assays, indicating a similar sensitivity to and specificity of both real time assays. CONCLUSION: The data from this study highlight the need to confirm N gonorrhoeae positive Cobas Amplicor PCR results as an important part of the testing algorithm of all diagnostic laboratories utilising this assay.     

Changing sagittal plane body position during single-leg landings influences the risk of non-contact anterior cruciate ligament injury

Purpose

To examine the effects of different sagittal plane body positions during single-leg landings on biomechanics and muscle activation parameters associated with risk for anterior cruciate ligament (ACL) injury.

Methods

Twenty participants performed single-leg drop landings onto a force plate using the following landing styles: self-selected, leaning forward (LFL) and upright (URL). Lower extremity and trunk 3D biomechanics and lower extremity muscle activities were recorded using motion analysis and surface electromyography, respectively. Differences in landing styles were examined using 2-way Repeated-measures ANOVAs (sex × landing conditions) followed by Bonferroni pairwise comparisons.

Results

Participants demonstrated greater peak vertical ground reaction force, greater peak knee extensor moment, lesser plantar flexion, lesser or no hip extensor moments, and lesser medial and lateral gastrocnemius and lateral quadriceps muscle activations during URL than during LFL. These modifications of lower extremity biomechanics across landing conditions were similar between men and women.

Conclusions

Leaning forward while landing appears to protect the ACL by increasing the shock absorption capacity and knee flexion angles and decreasing anterior shear force due to the knee joint compression force and quadriceps muscle activation. Conversely, landing upright appears to be ACL harmful by increasing the post-impact force of landing and quadriceps muscle activity while decreasing knee flexion angles, all of which lead to a greater tibial anterior shear force and ACL loading. ACL injury prevention programmes should include exercise regimens to improve sagittal plane body position control during landing motions.