Updating the modified Thompson test by using whole-body bioluminescence imaging to replace traditional efficacy testing in experimental models of murine malaria.

BACKGROUND: Rodent malaria models are extensively used to predict treatment outcomes in human infections. There is a constant need to improve and refine these models by innovating ways to apply new scientific findings and cutting edge technologies. In addition, and in accordance with the three R's of animal use in research, in vivo studies should be constantly refined to avoid unnecessary pain and distress to the experimental animals by using preemptive euthanasia as soon as the main scientific study objective has been accomplished. METHODS: The new methodology described in this manuscript uses the whole-body bioluminescence signal emitted by transgenic, luciferase-expressing Plasmodium berghei parasites to assess the parasite load predicted parasitaemia (PLPP) in drug and control treated female ICR-CD1 mice infected with 1 × 105 luciferase-expressing P. berghei (ANKA strain) infected erythrocytes. This methodology can replace other time-consuming and expensive methods that are routinely used to measure parasitaemia in infected animals, such as Giemsa-stained thin blood smears and flow cytometry. RESULTS: There is a good correlation between whole-body bioluminescence signal and parasitaemia measured using Giemsa-stained thin blood smears and flow cytometry respectively in donor and study mice in the modified Thompson test. The algebraic formulas which represent these correlations can be successfully used to assess PLPP in donor and study mice. In addition, the new methodology can pinpoint sick animals 2-8 days before they would have been otherwise diagnosed based on behavioural or any other signs of malaria disease. CONCLUSIONS: The new method for predicting parasitaemia in the modified Thompson test is simple, precise, objective, and minimizes false positive results that can lead to the premature removal of animals from study. Furthermore, from the animal welfare perspective of replace, reduce, and refine, this new method facilitates early removal of sick animals from study as soon as the study objective has been achieved, in many cases well before the clinical signs of disease are present.

Satisfactory postoperative alignment following retrograde SIGN Fin nailing for femoral shaft fractures: A case-control study.

PURPOSE: In developing countries, long bone fractures following trauma are a significant contributor to morbidity, and operating room resources are often limited in these settings. The Surgical Implant Generation Network (SIGN) Fin nail may reduce the challenges of retrograde intramedullary nailing of femoral fractures without fluoroscopy. In contrast to the traditional SIGN nail placed in a retrograde fashion, the Fin nail does not require proximal interlocking screws. Instead, the nail achieves stability through an interference fit within the proximal femoral canal. The purpose of this study is to compare postoperative alignment in femoral shaft fractures treated with either a retrograde SIGN Fin nail or a standard retrograde SIGN nail. METHOD: Using the SIGN online surgical database, we identified all femoral shaft fractures treated with a retrograde SIGN Fin nail at 2 African hospitals. Two examiners independently classified fracture patterns using the Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association (AO/OTA) classification system. Using an on-screen protractor tool, postoperative coronal and sagittal plane alignment were measured and recorded as deviation from anatomic alignment (DFAA), with units in degrees. Available patient demographics and surgical details were also recorded. Fin nail cases were matched in a 1:1 ratio to retrograde standard SIGN nail cases based on AO/OTA fracture type. RESULTS: Twenty-eight retrograde Fin nail cases were identified, and 28 matched retrograde SIGN nail cases were selected. The Fin nail and retrograde SIGN nail groups were well matched in terms of demographics, AO/OTA fracture type, and surgical characteristics. There was no significant difference in postoperative coronal or sagittal plane alignment between the groups. There were no cases in either group of average postoperative malalignment >5° in any plane. CONCLUSION: The SIGN Fin nail appears to achieve satisfactory radiographic alignment without the need for proximal interlocking screws, making it an attractive implant for retrograde femoral shaft fracture fixation in resource-limited settings. Further research is required to validate these findings and determine long-term Fin nail clinical outcomes.

Use of In Vivo Imaging System Technology in Leishmania major BALB/c Mouse Ear Infection Studies.

Novel treatments for cutaneous leishmaniasis (CL) are needed, due to current lack of effective universal treatments, increasing resistance among the parasite, and toxic effects or impracticality of the current therapeutics. Models of direct infection with high number of Leishmania parasites in the current research of CL involving the BALB/c mouse or Golden Syrian Hamster are considered not suitable for the assessment of antileishmanial drug efficacy because of the lack of disease similarities with humans. The saliva of the sand fly vector is known to affect the host response to infection by the Leishmania parasite. Here, we build upon a previous BALB/c model infected with luciferase-expressing Leishmania major parasites. In the present study, we infect the ear dermis instead of the foot pad or base of the tail, and compare multiple methods of infection, using parasites alone or mixed with either bites from uninfected sand flies (Phlebotomus duboscqi Diptera Psychodidae:Neveu-Lemaire) or salivary gland sonicate from sand flies. Our data show a dose-response of bioluminescent signal (which represents the parasite load at the infection site), dermal lesion development, and Leishmania Donovan Units in liver and spleen. This in vivo L. major ear infection model, once optimized, can be used for assessing the efficacy of drug compounds that have been determined as very effective in the other, high inoculum CL models.

Chondroblastoma of bone in the extremities: a multicenter retrospective study.

BACKGROUND: Chondroblastoma is a rare benign cartilage tumor that commonly occurs in children and adolescents. This study was designed to review the epidemiologic characteristics and outcomes of surgical management in a large series of patients with extremity chondroblastoma. METHODS: We performed a multicenter retrospective analysis of 199 patients with extremity chondroblastoma. Clinical data, radiographic images, histological findings, treatment, and outcome were analyzed. RESULTS: There were 145 male patients and fifty-four female patients with a mean age of 18.0 years. The most commonly involved bone was the proximal part of the tibia (fifty-five patients [27.6%]), followed by the proximal part of the femur (fifty-two patients [26.1%]) and the distal part of the femur (thirty-eight patients [19.1%]). Prior to presentation, 73.4% (146 of 199 patients) experienced pain. The mean duration of pain and other symptoms was 8.7 months. The physis was open in 25.7%, it was closing in 22.2%, and it was closed in 52.1% of the patients at the time of presentation. One hundred and twenty-six patients had at least twenty-four months of follow-up; their mean follow-up duration was 62.1 months (range, twenty-four to 190 months). Initial treatment was curettage for 119 patients (94.4%) and en bloc resection for seven patients (5.6%). The local recurrence rate was 5.0% after curettage and 0% after resection. The only significant factor related to recurrence was the location of the lesion in the proximal part of the humerus (p = 0.001). CONCLUSIONS: Chondroblastoma occurs most frequently in the proximal part of the tibia and the proximal part of the femur with significant male predilection. In this series, recurrence was most frequent in the proximal part of the humerus. Our results suggest that curettage and bone-grafting provide favorable local control and satisfactory functional outcome for patients with this disease. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Preparticipation cardiovascular screening among National Collegiate Athletic Association Division I institutions.

BACKGROUND: Sudden cardiac arrest is the leading cause of death in competitive athletes during sport, and screening strategies for the prevention of sudden cardiac death are debated. The purpose of this study was to assess the incorporation of routine non-invasive cardiovascular screening (NICS), such as ECG or echocardiography, in Division I collegiate preparticipation examinations. METHODS: Cross-sectional survey of current screening practices sent to the head athletic trainer of all National Collegiate Athletic Association (NCAA) Division I football programmes listed in the National Athletic Trainers' Association directory. RESULTS: Seventy-four of 116 (64%) programmes responded. Thirty-five of 74 (47%) of responding schools have incorporated routine NICS testing. ECG is the primary modality for NICS in 31 (42%) of schools, and 17 (49%) also utilise echocardiography. Sixty-four per cent of the programmes that do NICS routinely screen their athletes only once as incoming freshmen. Of institutions that do not conduct NICS, American Heart Association guidelines against routine NICS and cost were the most common reasons reported. CONCLUSIONS: While substantial debate exists regarding protocols for cardiovascular screening in athletes, nearly half of NCAA Division I football programmes in this study already incorporate NICS into their preparticipation screening programme. Additional research is needed to understand the impact of NICS in collegiate programmes.

Gastrointestinal temperature trends in football linemen during physical exertion under heat stress.

CONTEXT: Exertional heat stroke is the third leading cause of death in US athletes. Elevations in core temperature in the digestive tract (TGI) have correlated with core temperature and are possible indicators of those at increased risk of heat stroke. OBJECTIVE: The primary objective was to compare a.m. vs. p.m. TGI variation in collegiate football linemen during intense "two-a-day" preseason practice. A secondary objective was to compare longitudinal TGI in offensive and defensive linemen. DESIGN: Cross-sectional observational study. SETTING: Division I Intercollegiate Athletics Football Program. INTERVENTIONS: TGI was monitored during consecutive preseason sessions. MAIN OUTCOME MEASUREMENTS: TGI, heat illness, weight changes, environmental stress, and subjective symptoms. RESULTS: Mean TGI were 37.8°C and 38.3°C during a.m. and p.m. practices, respectively. The a.m. practices revealed higher TGI gain (1.8°C) compared to p.m. (1.4°C). The p.m. practices had higher maximum TGI than a.m. practices (39.1°C versus 38.8, P=0.0001). Mean time to maximum temperature (Tmax) was 1 hr and 30 min for a.m. and 1 hr and 22 min for p.m. practices. Offensive linemen trended toward higher mean TGI than defensive players (38.0°C vs. 36.7°C, P = 0.069). The rate of rise in TGI was significantly greater in a.m. practices. A decrease in rate of TGI rise was seen from the first to last a.m. practices of the week (P = 0.004). CONCLUSION: Significant TGI elevations in asymptomatic athletes are common in extreme heat during football practice. Intense a.m. practices in full gear result in higher net temperature gain and rate of temperature gain than p.m. practices. Offensive linemen trended toward higher TGI than defensive linemen. As players acclimatized, a decrease in the rate of TGI increase was appreciable, particularly in a.m. practices. Appreciating cumulative heat stress and variations in heat stress related to scheduling of practice is critical.