Knee joint loading in knee osteoarthritis: influence of abdominal and thigh fat.

PubMed

Messier, Stephen P; Beavers, Daniel P; Loeser, Richard F; Carr, J Jeffery; Khajanchi, Shubham; Legault, Claudine; Nicklas, Barbara J; Hunter, David J; Devita, Paul

2014-09-01

Using three separate models that included total body mass, total lean and total fat mass, and abdominal and thigh fat as independent measures, we determined their association with knee joint loads in older overweight and obese adults with knee osteoarthritis (OA). Fat depots were quantified using computed tomography, and total lean and fat mass were determined with dual energy x-ray absorptiometry in 176 adults (age, 66.3 yr; body mass index, 33.5 kg·m) with radiographic knee OA. Knee moments and joint bone-on-bone forces were calculated using gait analysis and musculoskeletal modeling. Higher total body mass was significantly associated (P ≤ 0.0001) with greater knee compressive and shear forces, compressive and shear impulses (P < 0.0001), patellofemoral forces (P < 0.006), and knee extensor moments (P = 0.003). Regression analysis with total lean and total fat mass as independent variables revealed significant positive associations of total fat mass with knee compressive (P = 0.0001), shear (P < 0.001), and patellofemoral forces (P = 0.01) and knee extension moment (P = 0.008). Gastrocnemius and quadriceps forces were positively associated with total fat mass. Total lean mass was associated with knee compressive force (P = 0.002). A regression model that included total thigh and total abdominal fat found that both were significantly associated with knee compressive and shear forces (P ≤ 0.04). Thigh fat was associated with knee abduction (P = 0.03) and knee extension moment (P = 0.02). Thigh fat, consisting predominately of subcutaneous fat, had similar significant associations with knee joint forces as abdominal fat despite its much smaller volume and could be an important therapeutic target for people with knee OA.

Critical assessment of the anterolateral thigh flap donor site.

PubMed

Townley, W A; Royston, E C; Karmiris, N; Crick, A; Dunn, R L R

2011-12-01

The free anterolateral thigh flap (ALT) is now used as a 'workhorse flap'. The donor site morbidity is thought to be minimal, although most evidence derives from questionnaire-based studies rather than rigorous objective clinical assessment. In particular, robust quantitative data on thigh sensibility and quadriceps function is lacking. The aim of this study was to provide a comprehensive clinical assessment of donor site morbidity. We performed a prospective study of consecutive free ALT perforator flaps performed at Salisbury Foundation Trust between March 2008 and April 2010. The donor site was assessed at six months including a questionnaire (symptoms, function), scar analysis (Vancouver Scar Scale, VSS), and evaluation of quadriceps power and lateral thigh sensibility (compared with the contralateral unoperated thigh). One hundred ALT flaps were performed on 97 patients (mean age 46.8 years). The donor site was closed directly in 88 cases and using a split skin graft in 12 cases. At follow-up (n=68), tingling was the most common reported symptom (59%), whereas pain, itching and muscle herniation were reported infrequently. Donor site scars were mostly flat, pale and soft but widened. Pathological scarring was rare. Sensibility was reduced in donor thighs (p<0.001) and correlated with flap width but peak quadriceps contraction was similar between donor and unoperated thighs. There was a high throughput and diverse application of ALT flap reconstructions during the study period. Reduced sensibility was common around the scar but rarely troublesome. Quadriceps function was not affected even when dissection of intramuscular perforators was required. The ALT is a versatile flap that can deliver a large skin paddle with minimal impact on thigh function. Copyright © 2011 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Accuracy and Reliability of Marker-Based Approaches to Scale the Pelvis, Thigh, and Shank Segments in Musculoskeletal Models.

PubMed

Kainz, Hans; Hoang, Hoa X; Stockton, Chris; Boyd, Roslyn R; Lloyd, David G; Carty, Christopher P

2017-10-01

Gait analysis together with musculoskeletal modeling is widely used for research. In the absence of medical images, surface marker locations are used to scale a generic model to the individual's anthropometry. Studies evaluating the accuracy and reliability of different scaling approaches in a pediatric and/or clinical population have not yet been conducted and, therefore, formed the aim of this study. Magnetic resonance images (MRI) and motion capture data were collected from 12 participants with cerebral palsy and 6 typically developed participants. Accuracy was assessed by comparing the scaled model's segment measures to the corresponding MRI measures, whereas reliability was assessed by comparing the model's segments scaled with the experimental marker locations from the first and second motion capture session. The inclusion of joint centers into the scaling process significantly increased the accuracy of thigh and shank segment length estimates compared to scaling with markers alone. Pelvis scaling approaches which included the pelvis depth measure led to the highest errors compared to the MRI measures. Reliability was similar between scaling approaches with mean ICC of 0.97. The pelvis should be scaled using pelvic width and height and the thigh and shank segment should be scaled using the proximal and distal joint centers.

Clinical effects of thigh cuffs during a 7-day 6° head-down bed rest

NASA Astrophysics Data System (ADS)

Pavy-Le Traon, Anne; Maillet, Alain; Vasseur Clausen, Pascale; Custaud, Marc-Antoine; Alferova, Irina; Gharib, Claude; Fortrat, Jacques-Olivier

2001-08-01

Thigh cuffs are used by Russian cosmonauts to limit the fluid shift induced by space flight. A ground simulation using the head-down bed rest (HDBR) model was performed to assess the effects of thigh cuffs on clinical tolerance and orthostatic adaptation. 8 male healthy volunteers (32.4±1.9 years) participated twice in a 7-day HDBR — one time with thigh cuffs (worm daily from 9 am to 7 pm) (TC) and one time without (WTC). Orthostatic tolerance was assessed by a 10 minute stand test and by a LBNP test (5 min at -15, -30, -45 mmHg) before (BDC-1) and at the end of the HDBR period (R+1). Plasma volume was measured before and at the end of HDBR by the Evans blue dye dilution technique. Thigh cuffs limits headache due to fluid shift, as well as the loss in plasma volume (TC: -5.85±0.95%; WTC: -9.09±0.82%, p<0.05). The mean duration of the stand test (R+1) did not differ in the two group (TC 7.1±1.3 min; WTC 7.0±1.0 min). The increase in HR and decrease in diastolic blood pressure were slightly but significantly larger without thigh cuffs. Duration of the LBNP tests did not differ with thigh cuffs. Thigh cuffs limit the symptoms due to fluid shift and the loss in plasma volume. They partly reduced the increase in HR during orthostatic stress but had no effect on duration of orthostatic stress tests.

KNEE-JOINT LOADING IN KNEE OSTEOARTHRITIS: INFLUENCE OF ABDOMINAL AND THIGH FAT

PubMed Central

Messier, Stephen P.; Beavers, Daniel P.; Loeser, Richard F.; Carr, J. Jeffery; Khajanchi, Shubham; Legault, Claudine; Nicklas, Barbara J.; Hunter, David J.; DeVita, Paul

2014-01-01

Purpose Using three separate models that included total body mass, total lean and total fat mass, and abdominal and thigh fat as independent measures, we determined their association with knee-joint loads in older overweight and obese adults with knee osteoarthritis (OA). Methods Fat depots were quantified using computed tomography and total lean and fat mass determined with dual energy x-ray absorptiometry in 176 adults (age = 66.3 yr., BMI = 33.5 kg·m−2) with radiographic knee OA. Knee moments and joint bone-on-bone forces were calculated using gait analysis and musculoskeletal modeling. Results Higher total body mass was significantly associated (p ≤ 0.0001) with greater knee compressive and shear forces, compressive and shear impulses (p < 0.0001), patellofemoral forces (p< 0.006), and knee extensor moments (p = 0.003). Regression analysis with total lean and total fat mass as independent variables revealed significant positive associations of total fat mass with knee compressive (p = 0.0001), shear (p < 0.001), and patellofemoral forces (p = 0.01) and knee extension moment (p = 0.008). Gastrocnemius and quadriceps forces were positively associated with total fat mass. Total lean mass was associated with knee compressive force (p = 0.002). A regression model that included total thigh and total abdominal fat found both were significantly associated with knee compressive and shear forces (p ≤ 0.04). Thigh fat was associated with the knee abduction (p = 0.03) and knee extension moment (p = 0.02). Conclusions Thigh fat, consisting predominately of subcutaneous fat, had similar significant associations with knee joint forces as abdominal fat despite its much smaller volume and could be an important therapeutic target for people with knee OA. PMID:25133996

The efficacy of cryolipolysis treatment on arms and inner thighs.

PubMed

Wanitphakdeedecha, Rungsima; Sathaworawong, Angkana; Manuskiatti, Woraphong

2015-11-01

Cryolipolysis has emerged as a new non-invasive body contouring method using controlled cooling to selectively destroy fat cells. Previous studies demonstrated the safety and efficacy of cryolipolysis for the reduction of localized subcutaneous fat on abdomen and flanks. Recently, the new flat cup vacuum applicator has been developed to treat localized subcutaneous fat on arms and inner thighs. The objective of this study was to determine the efficacy of non-invasive cryolipolysis for body contouring with a flat cup vacuum applicator on arms and inner thighs. Twenty females with excess localized subcutaneous fat on arms or inner thighs received a single cryolipolysis treatment. Forty treatment areas have been treated including 10 arms and 30 inner thighs. Subjects were evaluated using standardized photographs and measurements of body weight and circumference of arms or inner thighs at baseline, 3-month, and 6-month follow-up visits. Physicians' evaluation and patient's satisfaction of clinical improvement were also measured. Of all 20 subjects, 17 (10 arms and 24 inner thighs) completed the treatment protocol and attended all follow-up visits. Three subjects were withdrawn from the study, 1 subject could not complete the treatment session due to pain and numbness during treatment, 1 subject became pregnant after treatment, and the other subject could not attend all required follow-up visits. There was significant circumference reduction of 0.41 and 0.72 cm at 3-month and 6-month follow-up visits (p = 0.017), respectively. Most of the patients were rated to have 1-25% improvement at 6 months after treatment and were satisfied with the treatment outcome. The new cryolipolysis flat cup vacuum applicator provided beneficial effects for circumferential reduction of arms and inner thighs.

Interface pressure is affected by slippage of bandages at thigh.

PubMed

Miyazaki, K; Hirai, M; Koyama, A; Iwata, H; Ohashi, M; Ota, A

2012-12-01

Very little is known about how compression bandages lose interface pressure. We hypothesized that the loss of interface pressure is correlated with the slippage of the bandages, and studied the interface pressure and slippage of three bandages over 8 hours. Twenty-Seven legs from 27 healthy volunteers were bandaged with short stretch bandages (SS), cohesive short stretch bandages (CS), and long stretch bandages (LS). Pressure sensors were placed above the ankle (B1), below the knee (D), and mid thigh (F). Interface pressures in a sitting position were recorded at the beginning, and 4 and 8 hours later. In 17 legs, the pressure sensor sites were marked, and their heights were measured on standing upright. SS and CS lost interface pressure quickly, but LS maintained pressure better than SS and CS at all sites. There was no pressure difference between SS and CS at the lower leg. However, CS maintained pressure better than SS at the mid thigh (44.6% vs. 54.4% pressure loss at 8 hours, respectively. P=0.037). There was a tendency toward less slippage with CS than SS at the mid thigh. In CS and LS, there was a linear correlation between the slippage of bandages and the interface pressure at the mid thigh (P <.01, in both). The interface pressure may be affected by the slippage of bandages at the thigh, but not at the lower leg. Cohesive short stretch bandages may exert their beneficial impact at the thigh.

Correlation between thigh pain and radiological findings with a proximally porous-coated stem.

PubMed

Kinov, Plamen; Radl, Roman; Zacherl, Maximilian; Leithner, Andreas; Windhager, Reinhard

2007-10-01

Thigh pain has been consistently reported with cementless hip arthroplasty. The correlation between thigh pain and radiological findings and the clinical significance of thigh pain have not been studied in any detail. We carried out a retrospective study to analyse the performance of a proximally porous-coated cementless femoral component. Ninety-eight total hip arthroplasties were followed up clinically and radiologically for an average of 33 months (range: 12 to 64) after operation. The clinical results were good or excellent in 85 cases (87%). Thirteen patients (13%) reported thigh pain at latest follow-up. Subsidence of the stem was recorded in 10 cases, cortical thickening occurred in 14 hips (14%), and 17 hips (17%) presented proximal osteopenia. Proximally, radiolucent lines were observed in 11 cases. Thigh pain correlated with radiolucent lines, femoral thickening, fibrous fixation and stem migration. Bone remodelling was noted to continue even five years after implantation. Our observations demonstrated bone ingrowth in the majority of the cases and a low incidence of thigh pain. The correlation between radiological changes and thigh pain suggests implant micromotion and migration in some hips. Patients with thigh pain, changes in the proximal femur and progressive subsidence need further clinical and radiological follow-up.

Hot-boning enhances cook yield of boneless skinless chicken thighs

USDA-ARS?s Scientific Manuscript database

Three experiments were conducted to evaluate effects of postmortem deboning time on cook yield of boneless skinless chicken thighs. In Experiment 1 (3 replications), chicken thigh meat was separated from bones at 0.45 (hot-bone), 2, and 24 h and trimmed to obtain iliotibialis muscle. The iliotibiali...

Sensate anterolateral thigh perforator flap for ischiatic sores reconstruction in meningomyelocele patients.

PubMed

Santanelli Di Pompeo, Fabio; Longo, Benedetto; Pagnoni, Marco; Laporta, Rosaria

2015-05-01

Recidivating pressure sores are a frequent complication in meningomyelocele patients because of their limitation in motility and their scarce ability to monitor the pressure applied on insensate areas while seated. We report the utilization of the sensate pedicled anterolateral thigh perforator flap for reconstruction of ischiatic sores in meningomyelocele patients. Between May 2011 and September 2013, five patients underwent transfer of a sensate pedicled anterolateral thigh flap, by an intermuscular passageway through the upper thigh, to reach the ischial defect. Flap was properly harvested from the thigh after assessment of the lateral cutaneous femoral nerve sensitive area with the Pressure-Specified Sensory Device. In all cases the flap reached the ischial defect harmlessly, healing was uneventful with no immediate nor late complications. Each patient showed persistence of sensitivity at the reconstructed area and no recurrent ischiatic sore was observed at mean follow-up of 26.4 months. The sensate pedicled anterolateral thigh flap is a valuable solution for coverage of recurrent ischial sores in meningomyelocele patients, in which pressure consciousness is fundamental. The intermuscular passageway allows to reduce the distance between flap's vascular pedicle origin and the ischial defect, hence to use the more reliable skin from the middle third of the anterolateral thigh. © 2014 Wiley Periodicals, Inc.

[Reseach development of vascular anatomy and preoperative design technology of anterolateral thigh flap].

PubMed

Duan, Jiazhang; He, Xiaoqing; Xu, Yongqing

2016-07-08

?To summarize the present status and progress of vascular anatomy and preoperative design technology of the anterolateral thigh flap. ?The relative researches focused on vascular anatomy and preoperative design technology of the anterolateral thigh flap were extensively reviewed, analyzed, and summarized. ?Vascular anatomy of the anterolateral thigh flap has been reported by numerous researchers, but perforators' location, origin, course, and the variation of the quantity have been emphasized. Meanwhile, the variation of descending branch, oblique branch, and lateral circumflex femoral artery has also been widely reported. Preoperative design technology of the anterolateral thigh flap includes hand-held Doppler, Color Doppler, CT angiography (CTA), magnetic resonance angiography, digital subtraction angiography, and digital technology, among which the hand-held Doppler is most widely used, and CTA is the most ideal, but each method has its own advantages and disadvantages. ?There is multiple variation of vascular anatomy of the anterolateral thigh flap. Though all kinds of preoperative design technologies can offer strong support to operation of anterolateral thigh flap, a simple, quick, precise, and noninvasive technology is the direction of further research.

Photons for Therapy: Targeted Photodynamic Therapy for Infected and Contaminated Wounds

DTIC Science & Technology

2004-09-01

caused by Staphylococcus aureus that had been allowed to grow in abscesses below the skin. Conjugate injected into the infected area together with...16] these authors showed that several strains responsible for periodontal disease were efficiently inactivated by visible light irradiation in the...counting. Rocchetta et al studied the growth of bioluminescent E. coli in the neutropenic mouse-thigh abscess model of infection [25]. They found that

Therapeutic effect of cefozopran (SCE-2787), a new parenteral cephalosporin, against experimental infections in mice.

PubMed Central

Iizawa, Y; Okonogi, K; Hayashi, R; Iwahi, T; Yamazaki, T; Imada, A

1993-01-01

The therapeutic effect of cefozopran (SCE-2787), a new semisynthetic parenteral cephalosporin, against experimental infections in mice was examined. Cefozopran was more effective than cefpiramide and was as effective as ceftazidime and cefpirome against acute respiratory tract infections caused by Klebsiella pneumoniae DT-S. In the model of chronic respiratory tract infection caused by K. pneumoniae 27, cefozopran was as effective as ceftazidime. The therapeutic effect of cefozopran against urinary tract infections caused by Pseudomonas aeruginosa P9 was superior to that of cefpirome and was equal to those of ceftazidime and cefclidin. In addition, cefozopran was more effective than ceftazidime and was as effective as flomoxef in a thigh muscle infection caused by methicillin-sensitive Staphylococcus aureus 308A-1. Against thigh muscle infections caused by methicillin-resistant S. aureus N133, cefozopran was the most effective agent. The potent therapeutic effect of cefozopran in those experimental infections in mice suggests that it would be effective against respiratory tract, urinary tract, and soft tissue infections caused by a variety of gram-positive and gram-negative bacteria in humans. PMID:8431004

78 FR 36304 - Proposed Information Collection (Hip and Thigh Conditions Disability Benefits Questionnaire...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-17

... and Thigh Conditions Disability Benefits Questionnaire) Activity: Comment Request AGENCY: Veterans... ``OMB Control No. 2900--NEW (Hip and Thigh Conditions Disability Benefits Questionnaire)'' in any...

Neural Network Model for Survival and Growth of Salmonella enterica Serotype 8,20:-:z6 in Ground Chicken Thigh Meat during Cold Storage: Extrapolation to Other Serotypes.

PubMed

Oscar, T P

2015-10-01

Mathematical models that predict the behavior of human bacterial pathogens in food are valuable tools for assessing and managing this risk to public health. A study was undertaken to develop a model for predicting the behavior of Salmonella enterica serotype 8,20:-:z6 in chicken meat during cold storage and to determine how well the model would predict the behavior of other serotypes of Salmonella stored under the same conditions. To develop the model, ground chicken thigh meat (0.75 cm(3)) was inoculated with 1.7 log Salmonella 8,20:-:z6 and then stored for 0 to 8 -8 to 16°C. An automated miniaturized most-probable-number (MPN) method was developed and used for the enumeration of Salmonella. Commercial software (Excel and the add-in program NeuralTools) was used to develop a multilayer feedforward neural network model with one hidden layer of two nodes. The performance of the model was evaluated using the acceptable prediction zone (APZ) method. The number of Salmonella in ground chicken thigh meat stayed the same (P > 0.05) during 8 days of storage at -8 to 8°C but increased (P < 0.05) during storage at 9°C (+0.6 log) to 16°C (+5.1 log). The proportion of residual values (observed minus predicted values) in an APZ (pAPZ) from -1 log (fail-safe) to 0.5 log (fail-dangerous) was 0.939 for the data (n = 426 log MPN values) used in the development of the model. The model had a pAPZ of 0.944 or 0.954 when it was extrapolated to test data (n = 108 log MPN per serotype) for other serotypes (S. enterica serotype Typhimurium var 5-, Kentucky, Typhimurium, and Thompson) of Salmonella in ground chicken thigh meat stored for 0 to 8 days at -4, 4, 12, or 16°C under the same experimental conditions. A pAPZ of ≥0.7 indicates that a model provides predictions with acceptable bias and accuracy. Thus, the results indicated that the model provided valid predictions of the survival and growth of Salmonella 8,20:-:z6 in ground chicken thigh meat stored for 0 to 8 days at -8 to

Characteristic MR image finding of squatting exercise-induced rhabdomyolysis of the thigh muscles.

PubMed

Yeon, Eung K; Ryu, Kyung N; Kang, Hye J; Yoon, So H; Park, So Y; Park, Ji S; Jin, Wook

2017-04-01

To describe the characteristic MRI appearance of squatting-induced rhabdomyolysis involving the thigh muscles. This study consisted of 10 cases obtained at 3 institutions from 2005 to 2015. A retrospective review was performed to obtain clinical information and MR scans for rhabdomyolysis of the thigh muscles. MRI was analyzed according to the distribution and degree of muscle involvement; the degree was assessed and graded as normal, mild or prominent. The mean patient age was 20.2 years (range, 15-24 years), and 7 of the 10 patients were male. All patients had history of excessive squatting action, suffered clinically from bilateral thigh pain and were confirmed to have rhabdomyolysis through analysis of serum creatine kinase (CK) levels. All of the patients (10/10) exhibited diffuse mild to prominent degree involvement of the anterior thigh muscles according to fluid-sensitive MR sequences. Among the anterior thigh muscles, the rectus femoris was spared in 8 patients (8/10) and mild degree involved in 2 patients (2/10). Thus, no cases exhibited prominent degree involvement of the rectus femoris muscle. Preservation of the rectus femoris muscle on MRI in squatting-induced rhabdomyolysis may be useful for differentiating rhabdomyolysis from other aetiologies. Advances in knowledge: Preservation of rectus femoris on MRI is distinguishable finding in squatting-induced rhabdomyolysis and reflects the functional anatomy of anterior thigh muscles.

Characteristic MR image finding of squatting exercise-induced rhabdomyolysis of the thigh muscles

PubMed Central

Yeon, Eung K; Kang, Hye J; Yoon, So H; Park, So Y; Park, Ji S; Jin, Wook

2017-01-01

Objective: To describe the characteristic MRI appearance of squatting-induced rhabdomyolysis involving the thigh muscles. Methods: This study consisted of 10 cases obtained at 3 institutions from 2005 to 2015. A retrospective review was performed to obtain clinical information and MR scans for rhabdomyolysis of the thigh muscles. MRI was analyzed according to the distribution and degree of muscle involvement; the degree was assessed and graded as normal, mild or prominent. Results: The mean patient age was 20.2 years (range, 15–24 years), and 7 of the 10 patients were male. All patients had history of excessive squatting action, suffered clinically from bilateral thigh pain and were confirmed to have rhabdomyolysis through analysis of serum creatine kinase (CK) levels. All of the patients (10/10) exhibited diffuse mild to prominent degree involvement of the anterior thigh muscles according to fluid-sensitive MR sequences. Among the anterior thigh muscles, the rectus femoris was spared in 8 patients (8/10) and mild degree involved in 2 patients (2/10). Thus, no cases exhibited prominent degree involvement of the rectus femoris muscle. Conclusion: Preservation of the rectus femoris muscle on MRI in squatting-induced rhabdomyolysis may be useful for differentiating rhabdomyolysis from other aetiologies. Advances in knowledge: Preservation of rectus femoris on MRI is distinguishable finding in squatting-induced rhabdomyolysis and reflects the functional anatomy of anterior thigh muscles. PMID:28181821

An analysis of postoperative thigh symptoms after minimally invasive transpsoas lumbar interbody fusion.

PubMed

Cummock, Matthew D; Vanni, Steven; Levi, Allan D; Yu, Yong; Wang, Michael Y

2011-07-01

The minimally invasive transpsoas interbody fusion technique requires dissection through the psoas muscle, which contains the nerves of the lumbosacral plexus posteriorly and genitofemoral nerve anteriorly. Retraction of the psoas is becoming recognized as a cause of transient postoperative thigh pain, numbness, paresthesias, and weakness. However, few reports have described the nature of thigh symptoms after this procedure. The authors performed a review of patients who underwent the transpsoas technique for lumbar spondylotic disease, disc degeneration, and spondylolisthesis treated at a single academic medical center. A review of patient charts, including the use of detailed patient-driven pain diagrams performed at equal preoperative and follow-up intervals, investigated the survival of postoperative thigh pain, numbness, paresthesias, and weakness of the iliopsoas and quadriceps muscles in the follow-up period on the ipsilateral side of the surgical approach. Over a 3.2-year period, 59 patients underwent transpsoas interbody fusion surgery. Of these, 62.7% had thigh symptoms postoperatively. New thigh symptoms at first follow-up visit included the following: burning, aching, stabbing, or other pain (39.0%); numbness (42.4%); paresthesias (11.9%); and weakness (23.7%). At 3 months postoperatively, these percentages decreased to 15.5%, 24.1%, 5.6%, and 11.3%, respectively. Within the patient sample, 44% underwent a 1-level, 41% a 2-level, and 15% a 3-level transpsoas operation. While not statistically significant, thigh pain, numbness, and weakness were most prevalent after L4-5 transpsoas interbody fusion at the first postoperative follow-up. The number of lumbar levels that were surgically treated had no clear association with thigh symptoms but did correlate directly with surgical time, intraoperative blood loss, and length of hospital stay. Transpsoas interbody fusion is associated with high rates of immediate postoperative thigh symptoms. While larger

Validation and Comparison of Accelerometers Worn on the Hip, Thigh, and Wrists for Measuring Physical Activity and Sedentary Behavior.

PubMed

Montoye, Alexander H K; Pivarnik, James M; Mudd, Lanay M; Biswas, Subir; Pfeiffer, Karin A

2016-01-01

Recent evidence suggests that physical activity (PA) and sedentary behavior (SB) exert independent effects on health. Therefore, measurement methods that can accurately assess both constructs are needed. To compare the accuracy of accelerometers placed on the hip, thigh, and wrists, coupled with machine learning models, for measurement of PA intensity category (SB, light-intensity PA [LPA], and moderate- to vigorous-intensity PA [MVPA]) and breaks in SB. Forty young adults (21 female; age 22.0 ± 4.2 years) participated in a 90-minute semi-structured protocol, performing 13 activities (three sedentary, 10 non-sedentary) for 3-10 minutes each. Participants chose activity order, duration, and intensity. Direct observation (DO) was used as a criterion measure of PA intensity category, and transitions from SB to a non-sedentary activity were breaks in SB. Participants wore four accelerometers (right hip, right thigh, and both wrists), and a machine learning model was created for each accelerometer to predict PA intensity category. Sensitivity and specificity for PA intensity category classification were calculated and compared across accelerometers using repeated measures analysis of variance, and the number of breaks in SB was compared using repeated measures analysis of variance. Sensitivity and specificity values for the thigh-worn accelerometer were higher than for wrist- or hip-worn accelerometers, > 99% for all PA intensity categories. Sensitivity and specificity for the hip-worn accelerometer were 87-95% and 93-97%. The left wrist-worn accelerometer had sensitivities and specificities of > 97% for SB and LPA and 91-95% for MVPA, whereas the right wrist-worn accelerometer had sensitivities and specificities of 93-99% for SB and LPA but 67-84% for MVPA. The thigh-worn accelerometer had high accuracy for breaks in SB; all other accelerometers overestimated breaks in SB. Coupled with machine learning modeling, the thigh-worn accelerometer should be considered when

Functional evaluation of anterolateral thigh flap donor sites: isokinetic torque comparisons for knee function.

PubMed

Tsuji, Naoko; Suga, Hirotaka; Uda, Koichi; Sugawara, Yasushi

2008-01-01

The anterolateral thigh flap is thought to have minor donor site morbidity, but muscle dissection is unavoidable when skin perforator vessels run through the vastus lateralis muscle. The purpose of this study was to investigate the functional problems associated with the anterolateral thigh flap donor site. We evaluated 12 patients who underwent free anterolateral thigh flap transfer between March 2003 and November 2005. A questionnaire and dynamic functional evaluation of the knee joint using the Biodex System were performed preoperatively and 6 months postoperatively. No patients reported any disturbance in their daily life. No significant differences were found between donor and normal thighs on isokinetic power tests of the quadriceps muscle. The function of the donor site after harvesting the anterolateral thigh flap was maintained. Damage to or functional disturbance of the donor site is minimal even if muscle is injured when harvesting the flap. (c) 2008 Wiley-Liss, Inc. Microsurgery, 2008

A comparison of patency and interventions in thigh versus Hemodialysis Reliable Outflow grafts for chronic hemodialysis vascular access.

PubMed

Brownie, Evan R; Kensinger, Clark D; Feurer, Irene D; Moore, Derek E; Shaffer, David

2016-11-01

�months, 1 year, and 3 years were 88%, 88%, and 70% for the thigh grafts and 53%, 43%, and 12% for the HeRO grafts. There were no differences in ischemic (P = .63) or infectious (P = .79) complications between the groups. Multivariable logistic regression demonstrated that after adjusting for follow-up time, HeRO grafts were associated with an increased number of interventions (P = .03). Thigh grafts have significantly better primary, assisted primary, and secondary patency compared with HeRO grafts. There is no significant difference between thigh grafts and HeRO grafts in ischemic or infectious complications. Our logistic regression model demonstrated an association between HeRO grafts and an increased number of interventions to maintain or restore patency. Although HeRO grafts may extend the use of the upper extremity, thigh grafts provide a more durable option for chronic hemodialysis. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Can hip and knee kinematics be improved by eliminating thigh markers?

PubMed Central

Schulz, Brian W.; Kimmel, Wendy L.

2017-01-01

Background Marker sets developed for gait analysis are often applied to more dynamic tasks with little or no validation, despite known complications of soft tissue artifact. Methods This study presents a comparison of hip and knee kinematics as calculated by five concurrently-worn tracking marker sets during eight different tasks. The first three marker sets were based on Helen Hayes but used 1) proximal thigh wands, 2) distal thigh wands, and 3) patellar markers instead of thigh wands. The remaining two marker sets used rigid clusters on the 4) thighs and shanks and 5) only shanks. Pelvis and foot segments were shared by all marker sets. The first three tasks were maximal femoral rotations using different knee and hip positions to quantify the ability of each marker set to capture this motion. The remaining five tasks were walking, walking a 1m radius circle, running, jumping, and lunging. Findings In general, few and small differences in knee and hip flexion-extension were observed between marker sets, while many and large differences in adduction-abduction and external-internal rotations were observed. The shank-only tracking marker set was capable of detecting the greatest hip external-internal rotation, yet only did so during dynamic tasks where greater hip axial motions would be expected. All data are available as supplementary material. Interpretation Marker set selection is critical to non-sagittal hip and knee motions. The shank-only tracking marker set presented here is a viable alternative that may improve knee and hip kinematics by eliminating errors from thigh soft tissue artifact. PMID:20493599

Ultrasound assessment of hamstring muscle size using posterior thigh muscle thickness.

PubMed

Abe, Takashi; Loenneke, Jeremy P; Thiebaud, Robert S

2016-05-01

Several studies have investigated the relationship between ultrasound-measured muscle thickness (MT) and individual muscle cross-sectional area (CSA) and muscle volume (MV) in extremity and trunk muscles; however, the hamstring muscle has not been studied. The purpose of this study was to examine the relationship between posterior thigh MT by ultrasound and the muscle CSA and MV of the hamstring obtained by magnetic resonance imaging (MRI). Ten young women aged 20-31 had MT measured by ultrasound at three sites on the medial anterior (50% of thigh length; TL) and posterior (50% and 70% of TL) aspects of the thigh. On the same day, a series of continuous muscle CSA along the thigh was measured by MRI. In each slice, the anatomical CSA of the hamstring (biceps femoris, semitendinosus and semimembranosus) and quadriceps muscle was analysed, and the CSAs at 50% and 70% of TL and maximal CSA of the hamstring (CSAmax ) were determined. MV was calculated by multiplying CSA by slice thickness. A significant correlation was observed between posterior 50% MT and 50% hamstring CSA (r = 0·848, P = 0·002) and between posterior 70% MT and 70% hamstring CSA (r = 0·679, P = 0·031). Posterior 50% MT (r = 0·732, P = 0·016) and 50% MTxTL (r = 0·873, P = 0·001) were also correlated to hamstring MV. Anterior:posterior 50% thigh MT ratio was correlated to MV ratio of quadriceps and hamstring muscles (r = 0·803, P = 0·005). Our results suggest that posterior thigh MT reflects hamstring muscle CSA and MV. The anterior:posterior MT ratio may serve as a surrogate for MV ratio of quadriceps and hamstring. © 2014 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Reconstruction of the pelvic floor and perineum with human acellular dermal matrix and thigh flaps following pelvic exenteration.

PubMed

Said, Hakim K; Bevers, Michael; Butler, Charles E

2007-12-01

Patients who undergo pelvic floor resection as treatment for recurrent cancer following radiation therapy have increased rates of complications, particularly if permanent prosthetic mesh is used for reconstruction. Human acellular dermal matrix (HADM), commonly used for reconstruction in other torso locations, is associated with lower rates of complications (including infection, adhesions and cutaneous exposure) than synthetic mesh. We describe an effective technique to reconstruct the pelvic floor and perineum with HADM and thigh-based flaps following pelvic exenteration and radical vulvectomy. A 75-year-old woman underwent radical resection of the pelvic floor and perineum to treat recurrent vulvar squamous cell carcinoma and osteoradionecrosis. The pelvic floor and perineal soft tissue defect were reconstructed with HADM (AlloDerm; LifeCell Corporation, Branchburg, NJ) and bilateral, thigh-based tissue flaps, respectively. Despite a large resection, previous irradiation therapy and bacterial contamination the wounds healed without complications. Reconstruction of pelvic floor defects using HADM is an option when wound conditions are unfavorable for the use of permanent prosthetic meshes.

The clinical application of anterolateral thigh flap.

PubMed

Lee, Yao-Chou; Chiu, Haw-Yen; Shieh, Shyh-Jou

2011-01-01

The anterolateral thigh flap can provide a large skin paddle nourished by a long and large-caliber pedicle and can be harvested by two-team work. Most importantly, the donor-site morbidity is minimal. However, the anatomic variations decreased its popularity. By adapting free-style flap concepts, such as preoperative mapping of the perforators and being familiar with retrograde perforator dissection, this disadvantage had been overcome gradually. Furthermore, several modifications widen its clinical applications: the fascia lata can be included for sling or tendon reconstruction, the bulkiness could be created by including vastus lateralis muscle or deepithelization of skin flap, the pliability could be increased by suprafascial dissection or primary thinning, the pedicle length could be lengthening by proximally eccentric placement of the perforator, and so forth. Combined with these technical and conceptual advancements, the anterolateral thigh flap has become the workhorse flap for soft-tissue reconstructions from head to toe.

Arterial injury associated with acute compartment syndrome of the thigh following blunt trauma.

PubMed

Suzuki, Takashi; Moirmura, Naoto; Kawai, Kousei; Sugiyama, Mitsugi

2005-01-01

Acute compartment syndrome of the thigh is a rare condition, and the basic causes of high pressure within a muscle compartment have been considered to be intramuscular haematoma and soft-tissue oedema. However, the importance of arterial injury has not been well recognized. Among 3658 blunt trauma patients admitted to our Level 1 Trauma Centre between 1994 and 2001, there were eight patients (nine thighs) who had undergone emergency fasciotomy and these were the subjects of the present study. Arteriography of the proximal lower limb had been performed after the fasciotomy in patients with prolonged hypotension and persistent bleeding from the fasciotomy wound. All the patients had sustained high-energy trauma, systemic hypotension and local trauma to the proximal lower limb. Among them, four (five thighs) had undergone arteriography and four (four thighs) were confirmed as having sustained arterial injuries. In those patients with definitive arterial injuries, the time from injury to the onset of the compartment syndrome was less than 5 h. Acute compartment syndrome of the thigh in blunt trauma patients may be the result of associated arterial injuries. It is suggested that patients with local trauma to the proximal lower limb who exhibit an acute compartment syndrome together with haemodynamic instability should undergo arteriography soon after fasciotomy.

Thigh-calf contact parameters for six high knee flexion postures: Onset, maximum angle, total force, contact area, and center of force.

PubMed

Kingston, David C; Acker, Stacey M

2018-01-23

In high knee flexion, contact between the posterior thigh and calf is expected to decrease forces on tibiofemoral contact surfaces, therefore, thigh-calf contact needs to be thoroughly characterized to model its effect. This study measured knee angles and intersegmental contact parameters in fifty-eight young healthy participants for six common high flexion postures using motion tracking and a pressure sensor attached to the right thigh. Additionally, we introduced and assessed the reliability of a method for reducing noise in pressure sensor output. Five repetitions of two squatting, two kneeling, and two unilateral kneeling movements were completed. Interactions of posture by sex occurred for thigh-calf and heel-gluteal center of force, and thigh-calf contact area. Center of force in thigh-calf regions was farther from the knee joint center in females, compared to males, during unilateral kneeling (82 and 67 mm respectively) with an inverted relationship in the heel-gluteal region (331 and 345 mm respectively), although caution is advised when generalizing these findings from a young, relatively fit sample to a population level. Contact area was larger in females when compared to males (mean of 155.61 and 137.33 cm 2 across postures). A posture main effect was observed in contact force and sex main effects were present in onset and max angle. Males had earlier onset (121.0°) and lower max angle (147.4°) with onset and max angles having a range between movements of 8° and 3° respectively. There was a substantial total force difference of 139 N between the largest and smallest activity means. Force parameters measured in this study suggest that knee joint contact models need to incorporate activity-specific parameters when estimating loading. Copyright © 2017 Elsevier Ltd. All rights reserved.

(1→3)-β-D-glucan aptamers labeled with technetium-99m: Biodistribution and imaging in experimental models of bacterial and fungal infection.

PubMed

de Sousa Lacerda, Camila Maria; Ferreira, Iêda Mendes; Dos Santos, Sara Roberta; de Barros, André Luís Branco; Fernandes, Simone Odília; Cardoso, Valbert Nascimento; de Andrade, Antero Silva Ribeiro

2017-03-01

Acid nucleic aptamers are RNA or DNA oligonucleotides capable of binding to a target molecule with high affinity and selectivity. These molecules are promising tools in nuclear medicine. Many aptamers have been used as targeting molecule of radiopharmaceuticals in preclinical studies. (1→3)-β-D-glucans are the main structural cell wall components of fungi and some bacteria. In the present study two radiolabeled (1→3)-β-D-glucan aptamers (seq6 and seq30) were evaluated to identity infectious foci caused by fungal or bacterial cells. Aptamer labeling with 99m Tc was performed by the direct method and biodistribution studies were accomplished in Swiss mice (n=6) infected in the right thigh muscle with Staphylococcus aureus or Candida albicans. A 99m Tc radiolabeled library consisting of oligonucleotides with random sequences was used as control. There was a higher uptake of 99m Tc radiolabeled aptamers in the infected thigh than in the left thigh muscle (non-infected) in the S. aureus infected animals. The target/non-target ratios were 3.17±0.22 for seq6 and 2.66±0.10 for seq30. These ratios were statistically higher than the value (1.54±0.05) found for the radiolabeled library (control). With regard to biodistribution, no statistical difference was verified between aptamers and control uptakes in the infection foci in the C. albicans infected animals. The target/non-target ratios were 1.53±0.03, 1.64±0.12 and 1.08±0.02 for radiolabeled library, seq6 and seq30, respectively. Scintigraphic imaging of infected foci using radiolabeled aptamers was possible only for S. aureus infected mice. Seq6 and seq30 aptamers proved to be inefficient for diagnosis of C. albicans infection. Nevertheless, their applicability for diagnosis of S. aureus and other bacterial infections by scintigraphy should be further explored. Copyright © 2016 Elsevier Inc. All rights reserved.

The Clinical Application of Anterolateral Thigh Flap

PubMed Central

Lee, Yao-Chou; Chiu, Haw-Yen; Shieh, Shyh-Jou

2011-01-01

The anterolateral thigh flap can provide a large skin paddle nourished by a long and large-caliber pedicle and can be harvested by two-team work. Most importantly, the donor-site morbidity is minimal. However, the anatomic variations decreased its popularity. By adapting free-style flap concepts, such as preoperative mapping of the perforators and being familiar with retrograde perforator dissection, this disadvantage had been overcome gradually. Furthermore, several modifications widen its clinical applications: the fascia lata can be included for sling or tendon reconstruction, the bulkiness could be created by including vastus lateralis muscle or deepithelization of skin flap, the pliability could be increased by suprafascial dissection or primary thinning, the pedicle length could be lengthening by proximally eccentric placement of the perforator, and so forth. Combined with these technical and conceptual advancements, the anterolateral thigh flap has become the workhorse flap for soft-tissue reconstructions from head to toe. PMID:22567234

Effect of magnesium on reactive oxygen species production in the thigh muscles of broiler chickens.

PubMed

Liu, Y X; Guo, Y M; Wang, Z

2007-02-01

1. The objective of the present study was to investigate the effect of magnesium (Mg) on reactive oxygen species (ROS) production in the thigh muscles of broiler chickens. A total of 96 1-d-old male Arbor Acre broiler chickens were randomly allocated into two groups, fed either on low-Mg or control diets containing about 1.2 g/kg or 2.4 g Mg/kg dry matter. 2. The low-Mg diet significantly increased malondialdehyde (MDA) concentration and decreased glutathione (GSH) in the thigh muscles of broiler chickens. ROS production in the thigh muscle homogenate was significantly higher in the low-Mg group than in the control group. Compared with the control, muscle Mg concentration of broiler chickens from the low-Mg group decreased by 9.5%. 3. Complex II and III activities of the mitochondrial electron transport chain in broilers on low-Mg diet increased by 23 and 35%, respectively. Significant negative correlations between ROS production and the activities of mitochondrial electron transport chain (ETC) complexes were observed. 4. The low-Mg diet did not influence contents of iron (Fe) or calcium (Ca) in the thigh muscles of broiler chickens and did not influence unsaturated fatty acid composition (except C18:2) in the thigh muscles. 5. A low-Mg diet decreased Mg concentration in the thigh muscles of broiler chickens and then induced higher activities of mitochondrial ETC, consequently increasing ROS production. These results suggest that Mg modulates the oxidation-anti-oxidation system of the thigh muscles at least partly through affecting ROS production.

Selective training-induced thigh muscles hypertrophy in professional road cyclists.

PubMed

Hug, François; Marqueste, Tanguy; Le Fur, Yann; Cozzone, Patrick J; Grélot, Laurent; Bendahan, David

2006-07-01

Muscular adaptations linked to a high volume and intensity of training have been scarcely reported. We aimed at documenting, using MRI, the cross-sectional area changes associated with a high volume and intensity of training in 11 thigh muscles of a population of professional road cyclists as compared with sport science students. We were also interested in determining, whether selective muscle hypertrophy in professional road cyclists, if any, was correlated to selective exercise-induced T (2) changes during a pedaling exercise on a cycloergometer. Cross-sectional area of 11 thigh muscles was quantified in sixteen subjects (i.e. eight professional road cyclists and eight sport science students) using MRI. In addition, transverse relaxation times (T (2)) were measured before and just after a maximal standardized constant-load exercise in order to investigate exercise-related T (2) changes in these muscles. Professional road cyclists had a significantly higher relative amount of muscle (including the whole set of thigh muscles, 90.5+/-3.3%) as compared to controls (81.6+/-7.3%). Regarding relative values expressed with respect to the total thigh muscles CSA, Vastus lateralis and Biceps femoris CSA were significantly larger in cyclists whereas CSA of the Vastus intermedius was smaller. However, this selective hypertrophy was not correlated to the exercise-induced T (2)-increase. We have reported, for the first time, a selective hypertrophy of Vastus lateralis and Biceps femoris in professional road cyclists confirming their involvement in pedaling task and suggesting a possible cause-effect relationship between muscle activation and hypertrophy, associated with a specific pedaling skill.

[COMPARISON OF REPAIR EFFECT BETWEEN CHIMERIC ANTEROLATERAL THIGH FLAP AND SERIES-WOUND FLAPS FOR DEFECT AFTER RESECTION OF ORAL AND MAXILLOFACIAL CANCER].

PubMed

Yang, Heping; Zhang, Hongwu; Chen, Haidi; Yang, Shuxiong; Wang, Jun; Hu, Dawang

2016-04-01

To compare the effectiveness of complex defects repair between using chimeric anterolateral thigh flap and series-wound flaps after resection of oral and maxillofacial cancer. After resection of oral and maxillofacial cancer, defect was repaired with chimeric anterolateral thigh flap in 39 patients between January 2011 and July 2014 (chimeric anterolateral thigh flap group); and defect was repaired with series-wound flaps in 35 patients between January 2009 and December 2010 (series-wound flaps group). There was no significant difference in gender, age, duration of disease, tumor type, tumor staging, defect location, and defect area between 2 groups (P > 0.05). The operation time, flap harvesting and microvascular anastomosis time, stomach tube extraction time, and oral feeding time were recorded and compared between 2 groups, and postoperative complications were observed; the effectiveness was evaluated according to clinical efficacy evaluation table of bone and soft tissue defects reconstruction surgery in oral and maxillofacial region. Vascular crisis occurred in 2 cases of chimeric anterolateral thigh flap group, and 4 cases of series-wound flaps group. Partial necrosis appeared at distal end of a series-wound flaps, and oral fistula and infection developed in 3 series-wound flaps. The other flaps and the grafted skin at donor site survived; wounds at recipient site healed by first intention. The operation time, stomach tube extraction time, and oral feeding time of chimeric anterolateral thigh flap group were significantly shorter than those of series-wound flaps group (P < 0.05), while the flap harvesting and microvascular anastomosis time was significantly longer than that of series-wound flaps group (P < 0.05). The patients were followed up 1-5 years (mean, 2.5 years). At 3 months after operation, the appearance, patients' satisfaction, working conditions, oral closure function, chew, language performance, and swallowing scores of the chimeric anterolateral

Ultrasound-Guided Removal of an Infected Loose Body from the Quadriceps Muscle.

PubMed

Razdan, Rishi N; Dube, Tiffany; Specht, Neil

2008-01-01

We present the case of a 35 year-old male with pain and swelling in his right thigh. By CT and sonography, an abscess was localized to the deep, anteromedial, mid-thigh within the quadriceps muscle, along with a 1.3 cm loose body. The infected loose body was removed under ultrasound guidance without complications.

Concomitant Liposuction Reduces Complications of Vertical Medial Thigh Lift in Massive Weight Loss Patients.

PubMed

Schmidt, Manfred; Pollhammer, Michael S; Januszyk, Michael; Duscher, Dominik; Huemer, Georg M

2016-06-01

Medial thigh lift procedures in the massive weight loss population have been associated with significant complication rates. Liposuction-assisted medial thighplasty has recently been introduced as a technical advancement to improve outcomes. To date, no study is available directly comparing the traditional approach and this new technique. Here, the authors evaluate outcomes and complications of both techniques in a retrospective cohort study. Outcomes of 59 patients undergoing vertical medial thighplasty at the authors' institution between 2008 and 2014 were assessed retrospectively. Evaluated parameters include age, sex, body mass indices, method of weight loss, comorbidities, and complications (e.g., seroma, infection, wound dehiscence, hematoma, and surgical revision). Appropriate statistical analysis was performed. There were 29 patients in the excision-only group and 30 patients in the liposuction-assisted group (all women; average age, 41.5 years). The overall complication rate was significantly reduced in the liposuction-assisted group (13 percent versus 59 percent; p < 0.001). The incidence of individual complications such as seroma formation (zero patients versus 10 patients; p < 0.001) and wound infection (one patient versus eight patients; p = 0.01) was significantly less in the liposuction-assisted group. In addition, we observed a significantly shorter hospital stay (6.0 days versus 7.8 days), reduced number of follow-up visits (2.0 versus 4.4), and reduced time to drain removal (1.8 days versus 4.1 days; p < 0.001) in the liposuction-assisted group. Liposuction-assisted medial thighplasty led to a significant reduction of complications and faster recovery in the massive weight loss patient population. As a consequence, the excision-only vertical thigh lift has been completely abandoned in the authors' clinical practice. Therapeutic, III.

Delayed Carcass Deboning Results in Significantly Reduced Cook Yields of Boneless Skinless Chicken Thighs

USDA-ARS?s Scientific Manuscript database

Boneless skinless chicken thighs are a new deboned poultry product in the retail market. Three trials were conducted to investigate the effect of postmortem carcass deboning time on the cook yields of boneless skinless chicken thighs as well as boneless skinless chicken breasts. Broiler carcasses ...

Seasonal occurrence of migrant whimbrels and bristle-thighed curlews on the Yukon-Kuskokwim Delta, Alaska

USGS Publications Warehouse

Handel, Colleen M.; Dau, Christian P.

1988-01-01

Migrant Whimbrels (Numenius phaeopus) and Bristle-thighed Curlews (N. tahitiensis) were recorded during five summers along coastal tundra of the Yukon-Kuskokwim Delta, Alaska. From June to September, 1975-1979, 358 flocks totalling 1,265 curlews were observed; an additional 54 flocks were identified by vocalization alone. Among the 359 flocks identified to species, 52% were of Whimbrels, 47% were of Bristle-thighed Curlews, and 1% were of both species. Flocks as large as 48 Whimbrels and 33 Bristle-thighed Curlews were recorded, but 87% of the flocks contained five or fewer birds. During 2 years with early springs a few Whimbrels and Bristle-thighed Curlews were recorded on the delta in early June; these may have been late spring migrants, oversummering nonbreeders, or very early failed breeders. Whimbrel numbers peaked twice each summer, first in middle to late July and again in late August. These peaks probably consisted mainly of late failed breeders and of successful breeders with juveniles, respectively. The patterns of occurrence of Bristle-thighed Curlews were more complex, with up to three peaks in abundance each season, probably consisting of the following populational subclasses: (1) early failed breeders from late June to mid-July, (2) late failed breeders in late July, and (3) successful breeders and juveniles in early August. Most Bristle-thighed Curlews were gone by mid-August and Whimbrels, by early September. For both species the earliest juveniles were seen in late July in flocks with adults. The Yukon-Kuskokwim Delta is conservatively estimated to support several thousands of both Whimbrels and Bristle-thighed Curlews. This area is considered to be particularly important for Bristle-thighed Curlews because it is the primary of only two known areas used during migration between their nesting grounds in Alaska and the first known stop on their wintering grounds in the Hawaiian Island chain, a transoceanic distance of 3,800 km. Whimbrels are more

Gunshot wounds to the thigh. Evaluation of vascular and subclinical vascular injuries.

PubMed

Payne, W K; Gabriel, R A; Massoud, R P

1995-01-01

A retrospective review of 173 patient charts, angiograms, surgical reports, and plain radiographs were performed for all patients admitted with gunshot wounds to the thigh from May 1988 to January 1991 at Martin Luther King, Jr. Hospital. A zonal classification of gunshot wounds to the thigh was created and defined to determine if a zonal classification was predictive of a positive angiogram. Associations and relationships of patients with vascular injury are presented.

Left thigh phlegmon caused by Nocardia farcinica identified by 16S rRNA sequencing in a patient with leprosy: a case report.

PubMed

De Nardo, Pasquale; Giancola, Maria Letizia; Noto, Salvatore; Gentilotti, Elisa; Ghirga, Piero; Tommasi, Chiara; Bellagamba, Rita; Paglia, Maria Grazia; Nicastri, Emanuele; Antinori, Andrea; Corpolongo, Angela

2013-04-04

In recent years, Nocardia farcinica has been reported to be an increasingly frequent cause of localized and disseminated infections in the immunocompromised patient. However, recent literature is limited. We report a case of left thigh phlegmon caused by N. farcinica that occurred in a patient with leprosy undergoing treatment with prednisone for leprosy reaction. We describe the case of left thigh phlegmon caused by Nocardia farcinica in a 54-year-old Italian man affected by multi-bacillary leprosy. The patient had worked in South America for 11 years. Seven months after his return to Italy, he was diagnosed with leprosy and started multi-drug antibiotic therapy plus thalidomide and steroids. Then, during therapy with rifampicin monthly, minocycline 100 mg daily, moxifloxacin 400 mg daily, and prednisone (the latter to treat type 2 leprosy reaction), the patient complained of high fever associated with erythema, swelling, and pain in the left thigh. Therefore, he was admitted to our hospital with the clinical suspicion of cellulitis. Ultrasound examination and Magnetic Resonance Imaging showed left thigh phlegmon. He was treated with drainage and antibiotic therapy (meropenem and vancomycin replaced by daptomycin). The responsible organism, Nocardia farcinica, was identified by 16S rRNA sequencing in the purulent fluid taken out by aspiration. The patient continued treatment with intravenous trimethoprim/sulfamethoxazole and imipenem followed by oral trimethoprim/sulfamethoxazole and moxifloxacin. A whole-body computed tomography did not reveal dissemination to other organs like the lung or brain.The patient was discharged after complete remission. Oral therapy with trimethoprim/sulfamethoxazole, moxifloxacin, rifampicin monthly, clofazimine and thalidomide was prescribed to be taken at home. One month after discharge from the hospital the patient is in good clinical condition with complete resolution of the phlegmon. N. farcinica is a rare infectious agent that

Outcomes of using a modified anteromedial thigh perforator flap for repairing the anterolateral thigh free flap donor site: A retrospective clinical review.

PubMed

Zhou, Xiao; Wang, Jin; Qiang, Li; Rui, Yongjun; Xue, Mingyu

2018-04-01

The anterolateral thigh (ALT) flap plays an essential part in plastic and reconstructive surgery. However, repair of the anterolateral donor site has not been the focus of the clinicians.To assess the clinical value and feasibility of using a modified anteromedial thigh (AMT) perforator flap for repairing the ALT free flap donor site.In this retrospective study, 16 ALT flaps were transferred to resurface large soft-tissue defects (ranged from 7 × 5 to 13 × 8 cm) in the foot or hand from June 2012 to March 2013. The donor sites were repaired with an advancement flap pedicled with an AMT perforator. Sensation within the advancement flap, return-to-work (RTW) time, the aesthetic appearance of the donor sites, and functional recovery were measured.All 15 flaps survived completely without necrosis. One flap developed partial necrosis in the tip but healed with dressing changes after 1 week. The medain follow-up period was 3.5 months (range, 3-6 months). The average median time was 9.5 weeks (range 8-13 weeks). There was no numbness of the advancement flap. Additionally, there was no specific complication at both the recipient and donor sites. Thigh quadriceps muscle strength and activities of the knee were normal. All patients were satisfied with the aesthetic outcome postoperatively at the 3-month to 6-month follow-up.The modified advancement flap pedicled with an AMT perforator is an ideal option for repairing the anterolateral donor site.

Microvascular anastomosis simulation using a chicken thigh model: Interval versus massed training.

PubMed

Schoeff, Stephen; Hernandez, Brian; Robinson, Derek J; Jameson, Mark J; Shonka, David C

2017-11-01

To compare the effectiveness of massed versus interval training when teaching otolaryngology residents microvascular suturing on a validated microsurgical model. Otolaryngology residents were placed into interval (n = 7) or massed (n = 7) training groups. The interval group performed three separate 30-minute practice sessions separated by at least 1 week, and the massed group performed a single 90-minute practice session. Both groups viewed a video demonstration and recorded a pretest prior to the first training session. A post-test was administered following the last practice session. At an academic medical center, 14 otolaryngology residents were assigned using stratified randomization to interval or massed training. Blinded evaluators graded performance using a validated microvascular Objective Structured Assessment of Technical Skill tool. The tool is comprised of two major components: task-specific score (TSS) and global rating scale (GRS). Participants also received pre- and poststudy surveys to compare subjective confidence in multiple aspects of microvascular skill acquisition. Overall, all residents showed increased TSS and GRS on post- versus pretest. After completion of training, the interval group had a statistically significant increase in both TSS and GRS, whereas the massed group's increase was not significant. Residents in both groups reported significantly increased levels of confidence after completion of the study. Self-directed learning using a chicken thigh artery model may benefit microsurgical skills, competence, and confidence for resident surgeons. Interval training results in significant improvement in early development of microvascular anastomosis skills, whereas massed training does not. NA. Laryngoscope, 127:2490-2494, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Spontaneous thigh hematoma associated with diclofenac.

PubMed

Salemis, Nikolaos S

2009-01-01

Spontaneous nongastrointestinal bleeding in patients treated with nonsteroidal anti-inflammatory drugs is an extremely rare occurrence. Herein, the case of a 60-year-old woman with severe bilateral hip osteoarthritis treated with diclofenac sodium, who presented with manifestations of a spontaneous hematoma of the right thigh, is described. There was no history of trauma or family history of bleeding disorder. Thorough investigation excluded a hemorrhagic disorder. The patient was treated conservatively with success and was advised to discontinue diclofenac.

Hemodialysis Reliable Outflow (HeRO) device in end-stage dialysis access: a decision analysis model.

PubMed

Dageforde, Leigh Anne; Bream, Peter R; Moore, Derek E

2012-09-01

The Hemodialysis Reliable Outflow (HeRO) dialysis access device is a permanent tunneled dialysis graft connected to a central venous catheter and is used in patients with end-stage dialysis access (ESDA) issues secondary to central venous stenosis. The safety and effectiveness of the HeRO device has previously been proven, but no study thus far has compared the cost of its use with tunneled dialysis catheters (TDCs) and thigh grafts in patients with ESDA. A decision analytic model was developed to simulate outcomes for patients with ESDA undergoing placement of a HeRO dialysis access device, TDC, or thigh graft. Outcomes of interest were infection, thrombosis, and ischemic events. Baseline values, ranges, and costs were determined from a systematic review of the literature. Total costs were based on 1 year of post-procedure outcomes. Sensitivity analyses were conducted to test model strength. The HeRO dialysis access device is the least costly dialysis access with an average 1-year cost of $6521. The 1-year cost for a TDC was $8477. A thigh graft accounted for $9567 in a 1-year time period. The HeRO dialysis access device is the least costly method of ESDA. The primary determinants of cost in this model are infection in TDCs and leg ischemia necessitating amputation in thigh grafts. Further study is necessary to incorporate patient preference and quality of life into the model. Copyright © 2012 Elsevier Inc. All rights reserved.

Steady state and transient temperature distributions in the human thigh covered with a cooling pad

NASA Technical Reports Server (NTRS)

Leo, R. J.; Shitzer, A.; Chato, J. C.; Hertig, B. A.

1971-01-01

An analytical and experimental study was done on the performance of cooling pads attached to a human thigh. Each cooling pad consisted of a long, water cooled tube formed into a serpentine shape with uniform spacing between the parallel sections. The analytical work developed a cylindrical model for the human thigh. The transient times predicted by this model ranged from 25 to 80 minutes, which is reasonably close to the experimental results. Calculated and measured steady state temperature profiles were in fair agreement. The transient times associated with a change from a high metabolic rate of 1800 Btu/hr (528 w) to a low level of 300 Btu/hr (88 w), were found to be about 120 minutes. A change from 300 Btu/hr (264 w) to 300 Btu/hr (88 w) resulted in 90 to 100 minute transients. However, the transient times for a change in metabolic rate in the opposite direction from 300 Btu/hr (88 w) to 1800 Btu/hr (528 w) were 40 to 60 minutes.

Augmented reality and dynamic infrared thermography for perforator mapping in the anterolateral thigh

PubMed Central

Cifuentes, Ignacio Javier; Dagnino, Bruno Leonardo; Salisbury, María Carolina; Perez, María Eliana; Ortega, Claudia; Maldonado, Daniela

2018-01-01

Dynamic infrared thermography (DIRT) has been used for the preoperative mapping of cutaneous perforators. This technique has shown a positive correlation with intraoperative findings. Our aim was to evaluate the accuracy of perforator mapping with DIRT and augmented reality using a portable projector. For this purpose, three volunteers had both of their anterolateral thighs assessed for the presence and location of cutaneous perforators using DIRT. The obtained image of these “hotspots” was projected back onto the thigh and the presence of Doppler signals within a 10-cm diameter from the midpoint between the lateral patella and the anterior superior iliac spine was assessed using a handheld Doppler device. Hotspots were identified in all six anterolateral thighs and were successfully projected onto the skin. The median number of perforators identified within the area of interest was 5 (range, 3–8) and the median time needed to identify them was 3.5 minutes (range, 3.3–4.0 minutes). Every hotspot was correlated to a Doppler sound signal. In conclusion, augmented reality can be a reliable method for transferring the location of perforators identified by DIRT onto the thigh, facilitating its assessment and yielding a reliable map of potential perforators for flap raising. PMID:29788686

Augmented reality and dynamic infrared thermography for perforator mapping in the anterolateral thigh.

PubMed

Cifuentes, Ignacio Javier; Dagnino, Bruno Leonardo; Salisbury, María Carolina; Perez, María Eliana; Ortega, Claudia; Maldonado, Daniela

2018-05-01

Dynamic infrared thermography (DIRT) has been used for the preoperative mapping of cutaneous perforators. This technique has shown a positive correlation with intraoperative findings. Our aim was to evaluate the accuracy of perforator mapping with DIRT and augmented reality using a portable projector. For this purpose, three volunteers had both of their anterolateral thighs assessed for the presence and location of cutaneous perforators using DIRT. The obtained image of these "hotspots" was projected back onto the thigh and the presence of Doppler signals within a 10-cm diameter from the midpoint between the lateral patella and the anterior superior iliac spine was assessed using a handheld Doppler device. Hotspots were identified in all six anterolateral thighs and were successfully projected onto the skin. The median number of perforators identified within the area of interest was 5 (range, 3-8) and the median time needed to identify them was 3.5 minutes (range, 3.3-4.0 minutes). Every hotspot was correlated to a Doppler sound signal. In conclusion, augmented reality can be a reliable method for transferring the location of perforators identified by DIRT onto the thigh, facilitating its assessment and yielding a reliable map of potential perforators for flap raising.

Tendon sheath fibroma in the thigh.

PubMed

Moretti, Vincent M; Ashana, Adedayo O; de la Cruz, Michael; Lackman, Richard D

2012-04-01

Tendon sheath fibromas are rare, benign soft tissue tumors that are predominantly found in the fingers, hands, and wrists of young adult men. This article describes a tendon sheath fibroma that developed in the thigh of a 70-year-old man, the only known tendon sheath fibroma to form in this location. Similar to tendon sheath fibromas that develop elsewhere, our patient's lesion presented as a painless, slow-growing soft tissue nodule. Physical examination revealed a firm, nontender mass with no other associated signs or symptoms. Although the imaging appearance of tendon sheath fibromas varies, our patient's lesion appeared dark on T1- and bright on T2-weighted magnetic resonance imaging. It was well marginated and enhanced with contrast.Histologically, tendon sheath fibromas are composed of dense fibrocollagenous stromas with scattered spindle-shaped fibroblasts and narrow slit-like vascular spaces. Most tendon sheath fibromas can be successfully removed by marginal excision, although 24% of lesions recur. No lesions have metastasized. Our patient's tendon sheath fibroma was removed by marginal excision, and the patient remained disease free 35 months postoperatively. Despite its rarity, tendon sheath fibroma should be included in the differential diagnosis of a thigh mass on physical examination or imaging, especially if it is painless, nontender, benign appearing, and present in men. Copyright 2012, SLACK Incorporated.

Emergency repair of upper extremity large soft tissue and vascular injuries with flow-through anterolateral thigh free flaps.

PubMed

Zhan, Yi; Fu, Guo; Zhou, Xiang; He, Bo; Yan, Li-Wei; Zhu, Qing-Tang; Gu, Li-Qiang; Liu, Xiao-Lin; Qi, Jian

2017-12-01

Complex extremity trauma commonly involves both soft tissue and vascular injuries. Traditional two-stage surgical repair may delay rehabilitation and functional recovery, as well as increase the risk of infections. We report a single-stage reconstructive surgical method that repairs soft tissue defects and vascular injuries with flow-through free flaps to improve functional outcomes. Between March 2010 and December 2016 in our hospital, 5 patients with severe upper extremity trauma received single-stage reconstructive surgery, in which a flow-through anterolateral thigh free flap was applied to repair soft tissue defects and vascular injuries simultaneously. Cases of injured artery were reconstructed with the distal trunk of the descending branch of the lateral circumflex femoral artery. A segment of adjacent vein was used if there was a second artery injury. Patients were followed to evaluate their functional recoveries, and received computed tomography angiography examinations to assess peripheral circulation. Two patients had post-operative thumb necrosis; one required amputation, and the other was healed after debridement and abdominal pedicle flap repair. The other 3 patients had no major complications (infection, necrosis) to the recipient or donor sites after surgery. All the patients had achieved satisfactory functional recovery by the end of the follow-up period. Computed tomography angiography showed adequate circulation in the peripheral vessels. The success of these cases shows that one-step reconstructive surgery with flow-through anterolateral thigh free flaps can be a safe and effective treatment option for patients with complex upper extremity trauma with soft tissue defects and vascular injuries. Copyright © 2017. Published by Elsevier Ltd.

Pharmacodynamics of Imipenem in Combination with β-Lactamase Inhibitor MK7655 in a Murine Thigh Model

PubMed Central

Mavridou, Eleftheria; Melchers, Ria J. B.; van Mil, Anita C. H. A. M.; Mangin, E.; Motyl, Mary R.

2014-01-01

MK7655 is a newly developed beta-lactamase inhibitor of class A and class C carbapenemases. Pharmacokinetics (PK) of imipenem-cilastatin (IMP/C) and MK7655 were determined for intraperitoneal doses of 4 mg/kg to 128 mg/kg of body weight. MIC and pharmacodynamics (PD) studies of MK7655 were performed against several beta-lactamase producing Pseudomonas aeruginosa and Klebsiella pneumoniae strains to determine its effect in vitro and in vivo. Neutropenic mice were infected in each thigh 2 h before treatment with an inoculum of approximately 5 × 106 CFU. They were treated with IMP/C alone (every 2 hours [q2h], various doses) or in combination with MK7655 in either a dose fractionation study or q2h for 24 h and sacrificed for CFU determinations. IMP/MK7655 decreased MICs regarding IMP MIC. The PK profiles of IMP/C and MK7655 were linear over the dosing range studied and comparable with volumes of distribution (V) of 0.434 and 0.544 liter/kg and half-lives (t1/2) of 0.24 and 0.25 h, respectively. Protein binding of MK7655 was 20%. A sigmoidal maximum effect (Emax) model was fit to the PK/PD index responses. The effect of the inhibitor was not related to the maximum concentration of drug in serum (Cmax)/MIC, and model fits for T>MIC and area under the concentration-time curve (AUC)/MIC were comparable (R2 of 0.7 and 0.75), but there appeared to be no significant relationship of effect with dose frequency. Escalating doses of MK7655 and IMP/C showed that the AUC of MK7655 required for a static effect was dependent on the dose of IMP/C and the MIC of the strain, with a mean area under the concentration-time curve for the free, unbound fraction of the drug (fAUC) of 26.0 mg · h/liter. MK7655 shows significant activity in vivo and results in efficacy of IMP/C in otherwise resistant strains. The exposure-response relationships found can serve as a basis for establishing dosing regimens in humans. PMID:25403667

The relationships of waist and mid-thigh circumference with performance of college golfers

PubMed Central

Son, Seungbum; Han, Kunho; So, Wi-Young

2016-01-01

[Purpose] Our aim was to evaluate the relationships between waist and mid-thigh circumference, used as proxy measures of trunk and lower limb strengths, respectively, and selected parameters of driver and putting performance in Korean college golfers. [Subjects and Methods] The participants were 103 college golfers (81 male, 20 to 27 years old). Measurements of body composition, waist and mid-thigh circumference, and grip strength, as well as assessment of golf performance, including driver distance, driver swing speed, putting accuracy, and putting consistency, were performed at the golf performance laboratory at Konkuk University in Chungju-si, Republic of Korea. Average round score was obtained from 10 rounds of golf completed during the study period. The relationships between strength measures and golf performance were evaluated by partial correlation analysis, with adjustment for age, golf experience, and body mass index. [Results] Waist circumference did not correlate with any of the performance variables in both males and females. Mid-thigh circumference correlated with putting consistency (r = 0.364) in males and with putting consistency (r = 0.490) and accuracy (r = 0.547) in females. No other significant correlations between waist and mid-thigh circumference and golf performance were identified. [Conclusion] Lower limb strength may be an important component of putting performance. Further studies are needed to fully characterize the contributions of trunk strength to performance. PMID:27134346

The sensory territory of the lateral cutaneous nerve of the thigh as determined by anatomic dissections and ultrasound-guided blocks.

PubMed

Corujo, Alejandro; Franco, Carlo D; Williams, James M

2012-01-01

A femoral block sometimes fails to provide complete sensory anesthesia of the anterior aspect of middle and distal thigh, and a block of the lateral cutaneous nerve of the thigh (LCN) is often necessary to supplement it. The goal of this study was to demonstrate, both in the anatomy laboratory and in the clinical setting, a possible contribution of the LCN to the innervation of the anterior thigh. This was a prospective, observational study, including anatomic dissections and a clinical section in which 22 patients received an ultrasound-guided block of the LCN. The resulting area of anesthesia was determined 15 minutes later using pinprick examination. In 1 of 3 thigh dissections, we found a dominant LCN innervating most of the anterior aspect of the middle and distal thigh, areas that are usually attributed to the femoral nerve. In the clinical part of the study, 10 patients (45.5%) developed an area of anesthesia that extended to the medial aspect of the thigh and distally to the patella. Our results, coming from a small sample, seem to indicate that the LCN may contribute to the innervation of the anterior thigh in some cases. A block of the LCN could be considered when a femoral block has failed to produce the expected area of anesthesia.

Quality of breast and thigh meats when broilers are fed rations containing graded levels of sugar syrup.

PubMed

Hashim, I B; Hussein, A S; Afifi, H S

2013-08-01

The dietary energy for broiler chicken is provided through the inclusion of cereal grains and vegetable oil in the ration. The cost of corn is increasing exponentially, whereas sugar syrup (SS) is available with reasonable cost. Sugar syrup can be used as a substitute for starch/grains and vegetable oil. No research has been reported on the effect of SS on broiler meat quality. In this study, Hubbard commercial broiler chicks were fed a control basal diet (corn-soy basal diet on an ad libitum basis) alone or with graded levels of SS. A completely randomized design with 3 replications (n = 3, treatments = 4 with 4 subsamples per treatment) were used to investigate the effect of replacing part of the corn and oil in broiler chicken rations with graded levels of SS (5, 10, and 15%) on breast and thigh meat quality (proximate analysis, cooking loss, instrumental color, and texture and sensory properties). Rations containing up to 15% SS had a slight effect on proximate composition of raw and cooked broiler breast and thigh meats. Cooking loss of thigh meat decreased significantly with increasing SS but increased significantly for breast meats. No significant differences were detected (P > 0.05) among breast or thigh meats fed rations with a different level of SS on all sensory properties, except that cooked thigh meat had a slightly harder texture. Overall, results suggest that feeding broilers with SS rations (up to 15%) produced high-quality breast and thigh meats with minimal differences.

In Vivo Activities of Ceftolozane, a New Cephalosporin, with and without Tazobactam against Pseudomonas aeruginosa and Enterobacteriaceae, Including Strains with Extended-Spectrum β-Lactamases, in the Thighs of Neutropenic Mice

PubMed Central

Andes, D. R.

2013-01-01

Ceftolozane is a new cephalosporin with potent activity against Pseudomonas aeruginosa and Enterobacteriaceae. A neutropenic murine thigh infection model was used to determine which pharmacokinetic/pharmacodynamic index and magnitude drives the efficacy of ceftolozane with Gram-negative bacilli, to compare the rates of in vivo killing of P. aeruginosa by ceftolozane and ceftazidime, and to determine the impact of different ratios of ceftolozane plus tazobactam on Enterobacteriaceae containing extended-spectrum β-lactamases (ESBLs). Neutropenic mice had 106.2-7.1 CFU/thigh when treated with ceftolozane for 24 h with (i) various doses (3.12 to 1,600 mg/kg) and dosage intervals (3, 6, 12, and 24 h) against two Enterobacteriaceae strains, (ii) 0.39 to 800 mg/kg every 6 h for four Enterobacteriaceae and four P. aeruginosa strains, and (iii) 400 or 800 mg/kg with 2:1. 4:1, and 8:1 ratios of tazobactam against five Enterobacteriaceae strains with ESBLs. The pharmacokinetics of ceftolozane at 25, 100, and 400 mg/kg were linear with peak/dose values of 1.0 to 1.4 and half-lives of 12 to 14 min. T>MIC was the primary index driving efficacy. For stasis (1 log kill), T>MIC was 26.3% ± 2.1% (31.6% ± 1.6%) for wild-type Enterobacteriaceae, 31.1% ± 4.9% (34.8% ± 4.4%) for Enterobacteriaceae with ESBLs, and 24.0% ± 3.3% (31.5% ± 3.9%) for P. aeruginosa. At 200 mg/kg every 3 h, the rate of in vivo killing of P. aeruginosa was faster with ceftolozane than with ceftazidime (−0.34 to −0.41 log10 CFU/thigh/h versus −0.21 to −0.24 log10 CFU/thigh/h). The 2:1 ratio of ceftolozane with tazobactam was the most potent combination studied. The T>MIC required for ceftolozane is less than with other cephalosporins and may be due to more rapid killing. PMID:23274659

The adequate rocuronium dose required for complete block of the adductor muscles of the thigh.

PubMed

Fujimoto, M; Kawano, K; Yamamoto, T

2018-03-01

Rocuronium can prevent the obturator jerk during transurethral resection of bladder tumors. We investigated the adequate rocuronium dose required for complete block of the thigh adductor muscles, and its correlation with individual responses of the adductor pollicis muscle to rocuronium. Eleven patients scheduled for transurethral resection of bladder tumors under general anesthesia were investigated. After general anesthesia induction, neuromuscular monitoring of the adductor pollicis muscle and ultrasonography-guided stimulation of the obturator nerve was commenced. Rocuronium, 0.15 mg/kg, was repeatedly administered intravenously. The adequate rocuronium dose required for complete block of the thigh muscles, defined as the cumulative dose of rocuronium administered until that time, and its correlation with the first twitch response of the adductor pollicis muscle on train-of-four stimulation after initial rocuronium administration was analyzed. The rocuronium dose found adequate for complete block of the thigh muscles was 0.30 mg/kg in seven patients and 0.45 mg/kg in the remaining four patients, which did not correlate with the first twitch response. At the time of complete block of the thigh muscles, the neuromuscular blockade level of the adductor pollicis muscle varied greatly, although the level was never more profound than a post-tetanic count of 1. Although the response of the adductor pollicis muscle to rocuronium cannot be used to determine the adequate rocuronium dose required for complete block of the thigh muscles, intense blockade, with maintenance of post-tetanic count at ≤ 1 in the adductor pollicis muscle is essential to prevent the obturator jerk. © 2017 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Effect of postmortem deboning time on sensory descriptive flavor and texture profiles of cooked boneless skinless chicken thighs

USDA-ARS?s Scientific Manuscript database

Three replicate trials were conducted to investigate the effect of deboning time on sensory descriptive profiles of cooked boneless skinless thigh meat (iliotibialis, iliofibularis and the femoritibialis). Carcasses (42-d old birds) were obtained from a commercial processing plant. Thighs were hot-b...

Epidemiological and clinical outcome comparison of indirect ('strain') versus direct ('contusion') anterior and posterior thigh muscle injuries in male elite football players: UEFA Elite League study of 2287 thigh injuries (2001-2013).

PubMed

Ueblacker, Peter; Müller-Wohlfahrt, Hans-Wilhelm; Ekstrand, Jan

2015-11-01

Data regarding direct athletic muscle injuries (caused by a direct blunt or sharp external force) compared to indirect ones (without the influence of a direct external trauma) are missing in the current literature--this distinction has clinical implications. To compare incidence, duration of absence and characteristics of indirect and direct anterior (quadriceps) and posterior thigh (hamstring) muscle injuries. 30 football teams and 1981 players were followed prospectively from 2001 until 2013. The team medical staff recorded individual player exposure and time-loss injuries. Muscle injuries were defined as indirect or direct according to their injury mechanism. In total, 2287 thigh muscle injuries were found, representing 25% of all injuries. Two thousand and three were valid for further analysis, of which 88% were indirect and 12% direct. The incidence was eight times higher for indirect injuries (1.48/1000 h) compared to direct muscle injuries (0.19/1000 h) (p<0.01). Indirect muscle injuries caused 19% of total absence, and direct injuries 1%. The mean lay-off time for indirect injuries amounted to 18.5 days and differed significantly from direct injuries which accounted for 7 days (p<0.001). 60% of indirect injuries and 76% of direct injuries occurred in match situations. Foul play was involved in 7% of all thigh muscle injuries, as well as in 2% of indirect injuries and 42% of direct injuries. Muscle anterior and posterior thigh injuries in elite football are more frequent than have been previously described. Direct injuries causing time loss are less frequent than indirect ones, and players can usually return to full activity in under half the average time for an indirect injury. Foul play is involved in 7.5% of all thigh muscle injuries. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Free anterolateral thigh flap for reconstruction of major craniofacial defects.

PubMed

Amin, Ayman; Rifaat, Mohammed; Civantos, Francisco; Weed, Donald; Abu-Sedira, Mohammed; Bassiouny, Mahmoud

2006-02-01

Free-tissue transfer has revolutionized skull-base surgery by expanding the ability to perform cranial base resection and by improving the quality of reconstruction. The anterolateral thigh flap has come recently into use in the field of head and neck reconstruction. Its role in craniofacial and midface reconstruction has not been specifically defined. This study involved a total of 18 patients who were treated over a 5-year period from 1998 to 2003. Seventeen patients had locally advanced head and neck cancer, requiring craniofacial resection, and one patient had a complicated gun shot wound of the forehead. Thirteen patients were treated at the National Cancer Institute, Cairo University, Egypt, and five patients at the University of Miami, Florida. The patients presented with defects of the anterior skull base (5), lateral skull base (3), scalp and calvarium (3), and the midface (7). The anterolateral thigh flap was used as a myocutaneous flap in 11 cases and as a perforator fasciocutaneous flap in seven cases. Musculocutaneous perforators supplied the majority of flaps (17/18). Total flap survival occurred in 17 cases; one patient developed complete flap necrosis. The most commonly used recipient vessels were the facial vessels and the external jugular vein. Major complications included one case with meningitis; the patient died after failure of treatment. Another patient died 6 weeks postoperatively from pulmonary embolism. One patient developed CSF leak that stopped spontaneously. In addition, two patients developed minor wound dehiscence that healed spontaneously. The donor-site wound healed without problems except in two cases. One patient had an incomplete take of the skin graft; the other developed wound infection and superficial sloughing. Both wounds healed spontaneously. In addition to the feasibility of simultaneous flap harvesting with tumor resection, the flap's advantage in skull base reconstruction is its reliable blood supply, which can provide

[Deep skin infection with Scedosporium apiospermum-infection in a renal transplant patient].

PubMed

Strunk, T; Blume, J-H; Szeimies, R-M

2015-03-01

A 57-year-old immunosuppressed patient presented with multiple erythematous papules and pustules as well as isolated ulcerations on the right lower leg and subcutaneous nodules on the right thigh. The biopsy revealed granulomatous inflammation with numerous fungal hyphae, which were IDentified as Scedosporium apiospermum by PCR. He was treated with voriconazole 2 × 200 mg daily as well assurgical debridement. Scedosporium apiospermum is a rare pathogenic agent of deep mold fungus infections. Skin infections with Scedosporium apiospermum are underdiagnosed because of different clinical manifestations. In immunosuppressed patients, an infection represents a potentially life-threatening complication. Precise identification of the agent with introduction of antimycotic therapy appears to be pivotal to prevent fulminant disease.

Efficacy of thigh volume ratios assessed via stereovision body imaging as a predictor of visceral adipose tissue measured by magnetic resonance imaging

PubMed Central

Lee, Jane J; Freeland-Graves, Jeanne H; Pepper, M Reese; Yu, Wurong; Xu, Bugao

2014-01-01

Objectives The research examined the efficacy of regional volumes of thigh ratios assessed by stereovision body imaging (SBI) as a predictor of visceral adipose tissue measured by magnetic resonance imaging (MRI). Body measurements obtained via SBI also were utilized to explore disparities of body size and shape in men and women. Method 121 participants were measured for total/regional body volumes and ratios via SBI and abdominal subcutaneous and visceral adipose tissue areas by MRI. Results Thigh to torso and thigh to abdomen-hip volume ratios were the most reliable parameters to predict the accumulation of visceral adipose tissue depots compared to other body measurements. Thigh volume in relation to torso [odds ratios (OR) 0.44] and abdomen-hip (OR 0.41) volumes were negatively associated with increased risks of greater visceral adipose tissue depots, even after controlling for age, gender, and body mass index (BMI). Irrespective of BMI classification, men exhibited greater total body (80.95L vs. 72.41L), torso (39.26L vs. 34.13L), and abdomen-hip (29.01L vs. 25.85L) volumes than women. Women had higher thigh volumes (4.93L vs. 3.99L) and lower-body volume ratios [thigh to total body (0.07 vs. 0.05), thigh to torso (0.15 vs. 0.11), and thigh to abdomen-hip (0.20 vs. 0.15); p<0.05]. Conclusions The unique parameters of the volumes of thigh in relation to torso and abdomen-hip, by SBI were highly effective in predicting visceral adipose tissue deposition. The SBI provided an efficient method for determining body size and shape in men and women via total and regional body volumes and ratios. PMID:25645428

Efficacy of thigh volume ratios assessed via stereovision body imaging as a predictor of visceral adipose tissue measured by magnetic resonance imaging.

PubMed

Lee, Jane J; Freeland-Graves, Jeanne H; Pepper, M Reese; Yu, Wurong; Xu, Bugao

2015-01-01

The research examined the efficacy of regional volumes of thigh ratios assessed by stereovision body imaging (SBI) as a predictor of visceral adipose tissue measured by magnetic resonance imaging (MRI). Body measurements obtained via SBI also were utilized to explore disparities of body size and shape in men and women. One hundred twenty-one participants were measured for total/regional body volumes and ratios via SBI and abdominal subcutaneous and visceral adipose tissue areas by MRI. Thigh to torso and thigh to abdomen-hip volume ratios were the most reliable parameters to predict the accumulation of visceral adipose tissue depots compared to other body measurements. Thigh volume in relation to torso [odds ratios (OR) 0.44] and abdomen-hip (OR 0.41) volumes were negatively associated with increased risks of greater visceral adipose tissue depots, even after controlling for age, gender, and body mass index (BMI). Irrespective of BMI classification, men exhibited greater total body (80.95L vs. 72.41L), torso (39.26L vs. 34.13L), and abdomen-hip (29.01L vs. 25.85L) volumes than women. Women had higher thigh volumes (4.93L vs. 3.99L) and lower-body volume ratios [thigh to total body (0.07 vs. 0.05), thigh to torso (0.15 vs. 0.11), and thigh to abdomen-hip (0.20 vs. 0.15); P < 0.05]. The unique parameters of the volumes of thigh in relation to torso and abdomen-hip, by SBI were highly effective in predicting visceral adipose tissue deposition. The SBI provided an efficient method for determining body size and shape in men and women via total and regional body volumes and ratios. Am. J. Hum. Biol. 27:445-457, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Long-term outcome of using posterior-thigh fasciocutaneous flaps for the treatment of ischial pressure sores.

PubMed

Lin, Haodong; Hou, Chunlin; Chen, Aimin; Xu, Zhen

2010-08-01

Among the many difficult problems presented by patients with spinal cord injuries, management of ischial pressure ulcers remains challenging for reconstructive surgeons. This study describes the long-term outcome of using posterior-thigh fasciocutaneous flaps for the treatment of ischial pressure sores. Between January 1999 and June 2003, 12 patients with ischial sores were enrolled in this study. All the patients underwent early aggressive surgical debridement followed by surgical reconstruction with a laterally based posterior-thigh fasciocutaneous flap. The follow-up period ranged from 24 months to 97 months (mean, 62 months). All the flaps survived, and there were no partial flap losses. Primary-wound healing occurred in all the cases. In two patients, Grade II ischial pressure sores recurred 24 months and 27 months after the operation. There was no recurrence in the other 10 patients. The posterior-thigh fasciocutaneous pedicled flap was a good method for treating ischial bed sores. This flap could be used to treat recurrences observed after primary bed-sore treatment with other methods. The flap was easy to raise, and it did not cause any donor-site morbidity. The long-term outcome of using posterior-thigh fasciocutaneous flaps for the treatment of ischial pressure sores was generally good. (c) Thieme Medical Publishers.

Decreased torque and electromyographic activity in the extensor thigh muscles in chondromalacia patellae.

PubMed

Väätäinen, U; Airaksinen, O; Jaroma, H; Kiviranta, I

1995-01-01

The alterations in thigh muscle properties of chondromalacia patellae patients during isometric and dynamic endurance tests were studied using a variokinetic knee testing system linked to surface EMG. A total of 41 patients (chondromalacia group) with arthroscopically certified chondromalacia of the patella were studied. The control group consisted of 31 healthy adult volunteers with no history of knee pain or trauma. Peak torque values were 21% (p < 0.01) and force output values 25% (p < 0.05) lower on the symptomatic side of the chondromalacia group than in the control group. The decrease in the ratio between integrated EMG (IEMG) and measured force were found in all parts of the quadriceps femoris muscle in patients with chondromalacia of the patella in isometric extension. No change in the normalized IEMG levels of the thigh muscles were found between chondromalacia patients and controls in dynamic endurance test. The severity of the chondromalacia of the patella did not affect the level of electromyographic activation in thigh muscles. The ratio of normalized EMG levels of vastus medialis and vastus lateralis did not differ between the groups. The present study showed that chondromalacia patellae patients have reduced force and electromyographic activation levels of quadriceps femoris muscle. Especially, the explosive strength of the quadriceps femoris muscle is reduced.

Motor evoked responses from the thigh muscles to the stimulation of the upper limb nerves in patients with late poliomyelitis.

PubMed

Ertekin, Cumhur; On, Arzu Yagiz; Kirazli, Yeşim; Kurt, Tülay; Gürgör, Nevin

2002-04-01

To demonstrate a clear-cut M response recorded from the severely affected thigh muscles to the stimulation of the upper limb nerves in a serial of patients with late poliomyelitis. Fifteen patients with late poliomyelitis, 7 patients with spinal cord disorders and 11 control subjects were included. Evoked muscle responses were investigated in quadriceps femoris and/or thigh adductor muscles to the stimulation of the brachial plexus, median and ulnar nerves. Evoked muscle responses were obtained from the thigh muscles in all 12 late polio patients with proximal lower extremity involvement. The response could not be recorded from the thigh muscles neither in the 3 polio patients with upper extremity involvement nor in the healthy control subjects and in patients with other spinal cord disorders of anterior horn cell. It is proposed that the electrical stimulation of the arm nerves produce interlimb descending muscle responses in the severely affected atrophic thigh muscles of the patients with late polio. This finding suggests that there might be a focal and/or specific loss of inhibitory interneurons between injured and normal motor neurons and increased facilitatory synaptic action at the end of long propriospinal descending fibers in the case of late poliomyelitis.

Unilocular cystic lymphangioma of thigh-an extremely rare clinical entity.

PubMed

Thakur, Sudhir Kumar

2010-10-01

Majority of cystic lymphangiomas are multilocular and occur in neck and axilla. The cystic lymphangioma is also known as cystic hygroma. Unilocular cystic hygroma of neck and breast have been reported in literature and have been termed hydrocele of neck and breast respectively. However unilocular cystic hygroma of thigh is probably being reported for the first time.

Comparison of Activity Type Classification Accuracy from Accelerometers Worn on the Hip, Wrists, and Thigh in Young, Apparently Healthy Adults

ERIC Educational Resources Information Center

Montoye, Alexander H. K.; Pivarnik, James M.; Mudd, Lanay M.; Biswas, Subir; Pfeiffer, Karin A.

2016-01-01

The purpose of this article is to compare accuracy of activity type prediction models for accelerometers worn on the hip, wrists, and thigh. Forty-four adults performed sedentary, ambulatory, lifestyle, and exercise activities (14 total, 10 categories) for 3-10 minutes each in a 90-minute semi-structured laboratory protocol. Artificial neural…

Dissatisfaction among women with "thunder thighs" undergoing closed aspirative lipoplasty.

PubMed

Lewis, C M

1987-01-01

In our practice, we have uncovered a small series of female patients with "thunder thighs" who were dissatisfied with results of closed aspirative lipoplasty. The common problem appears to be unrealistic expectations. These patients expected a change in body habitus. This article reiterates the need for careful patient selection and preoperative information of what the procedure can and cannot accomplish.

Spontaneous Compartment Syndrome of the Thigh in the Absence of Trauma.

PubMed

Javedani, Parisa P; Ratnabalasuriar, Radhika; Grall, Kristi J H

2016-07-01

Compartment syndrome occurs when an increase in pressure results in vascular and functional impairment of the underlying nerve and muscles. Thigh compartment syndrome (TCS) is uncommon, but clinical suspicion warrants emergent surgical consultation and fasciotomy. We present a 42-year-old man evaluated for right lateral thigh pain, without a history of trauma, deep venous thrombosis (DVT), previous surgery, or intravenous drug use. He was febrile, tachycardic, with a mild leukocytosis, an elevated C-reactive protein level, and an elevated creatinine kinase level. Radiographs showed no abnormality and right lower extremity duplex ultrasound showed no DVT. A computed tomography scan of the right lower extremity was concerning for compartment syndrome. Surgical consultation was obtained, and the patient was taken to the operating room for fasciotomy. He was diagnosed with compartment syndrome intraoperatively. The patient was discharged on hospital day 10. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: TCS is exceedingly rare, especially in the absence of underlying traumatic and nontraumatic etiologies. The diagnosis is challenging because more elastic fascia with larger space in the thigh allows for accommodation of acute increases in pressure. Consequently, there may not be the expected acute rise in compartment pressures; increased compartment pressure may only be a late sign, when underlying neurovascular damage has already occurred. TCS is complicated by high morbidity and mortality. Emergent surgical consultation should be obtained when there is a high clinical suspicion for TCS, and limb-saving fasciotomy should not be delayed. This case shows the importance of a high level of suspicion for TCS in patients with no identifiable etiology and no historical risk factors for development of compartment syndrome, because TCS may not present with classic symptoms. Copyright © 2016 Elsevier Inc. All rights reserved.

Use of inferior gluteal artery and posterior thigh perforators in management of ischial pressure sores with limited donor sites for flap coverage.

PubMed

Unal, Cigdem; Ozdemir, Jale; Yirmibesoglu, Oktay; Yucel, Ergin; Agir, Hakan

2012-07-01

Reconstructive surgery for ischial pressure sore defects presents a challenge because of high rates of recurrence. The aim of this study was to describe the use of inferior gluteal artery (IGA) and posterior thigh perforators in management of ischial pressure sores with limited donor sites. Between September 2005 and 2009, 11 patients (9 male, 2 female) with ischial sores were operated by using IGA and posterior thigh perforator flaps. The data of patients included age, sex, cause of paraplegia, flap size, perforator of flap, previous surgeries, recurrences, complications, and postoperative follow-up. Nine IGA and 5 posterior thigh perforator flaps were used. Six patients presented with recurrent lesions, 5 patients were operated for sacral and contralateral ischial pressure sores previously. In 2 patients, IGA and posterior thigh perforator flaps were used in combination. Patients were followed for an average of 34.3 months. In 2 recurrent cases, readvancement of IGA perforator flap and gluteus maximus myocutaneous flap were treatment of choice. Treatment of patients with recurrent lesions or multiple pressure sores is challenging because of limited available flap donor sites. In this study, posterior thigh perforator flaps were preferred in patients in whom the previous donor site was the gluteal region. IGA perforator flaps were the treatment of choice in patients for whom posterior thigh region was previously used. Alternately, preserved perforators of previous conventional myocutaneous flaps enabled us to use these perforators in recurrences.

Deep onchocercomata close to the thigh bones of a Liberian patient.

PubMed

Kilian, H D

1988-12-01

During nodulectomies on a 53 year old Liberian woman, multiple onchocercomata were detected on the femur distal to the greater trochanter on both sides of the body. The nodules were attached to the periosteum. This location along the shaft of the thigh bone provides a further hint as to where clinically undetectable deep onchocercomata can be located.

Accuracy and precision of flash glucose monitoring sensors inserted into the abdomen and upper thigh compared with the upper arm.

PubMed

Charleer, Sara; Mathieu, Chantal; Nobels, Frank; Gillard, Pieter

2018-06-01

Nowadays, most Belgian patients with type 1 diabetes use flash glucose monitoring (FreeStyle Libre [FSL]; Abbott Diabetes Care, Alameda, California) to check their glucose values, but some patients find the sensor on the upper arm too visible. The aim of the present study was to compare the accuracy and precision of FSL sensors when placed on different sites. A total of 23 adults with type 1 diabetes used three FSL sensors simultaneously for 14 days on the upper arm, abdomen and upper thigh. FSL measurements were compared with capillary blood glucose (BG) measurements obtained with a built-in FSL BG meter. The aggregated mean absolute relative difference was 11.8 ± 12.0%, 18.5 ± 18.4% and 12.3 ± 13.8% for the arm, abdomen (P = .002 vs arm) and thigh (P = .5 vs arm), respectively. Results of Clarke error grid analysis for the arm and thigh were similar (zone A: 84.9% vs 84.5%; P = .6), while less accuracy was seen for the abdomen (zone A: 69.4%; P = .01). Apart from the first day, the accuracy of FSL sensors on the arm and thigh was more stable across the 14-day wear duration than accuracy of sensors on the abdomen, which deteriorated mainly during week 2 (P < .0005). The aggregated precision absolute relative difference was markedly lower for the arm/thigh (10.9 ± 11.9%) compared with the arm/abdomen (20.9 ± 22.8%; P = .002). Our results indicate that the accuracy and precision of FSL sensors placed on the upper thigh are similar to the upper arm, whereas the abdomen performed unacceptably poorly. © 2018 John Wiley & Sons Ltd.

Performance of thigh-mounted triaxial accelerometer algorithms in objective quantification of sedentary behaviour and physical activity in older adults.

PubMed

Wullems, Jorgen A; Verschueren, Sabine M P; Degens, Hans; Morse, Christopher I; Onambélé, Gladys L

2017-01-01

Accurate monitoring of sedentary behaviour and physical activity is key to investigate their exact role in healthy ageing. To date, accelerometers using cut-off point models are most preferred for this, however, machine learning seems a highly promising future alternative. Hence, the current study compared between cut-off point and machine learning algorithms, for optimal quantification of sedentary behaviour and physical activity intensities in the elderly. Thus, in a heterogeneous sample of forty participants (aged ≥60 years, 50% female) energy expenditure during laboratory-based activities (ranging from sedentary behaviour through to moderate-to-vigorous physical activity) was estimated by indirect calorimetry, whilst wearing triaxial thigh-mounted accelerometers. Three cut-off point algorithms and a Random Forest machine learning model were developed and cross-validated using the collected data. Detailed analyses were performed to check algorithm robustness, and examine and benchmark both overall and participant-specific balanced accuracies. This revealed that the four models can at least be used to confidently monitor sedentary behaviour and moderate-to-vigorous physical activity. Nevertheless, the machine learning algorithm outperformed the cut-off point models by being robust for all individual's physiological and non-physiological characteristics and showing more performance of an acceptable level over the whole range of physical activity intensities. Therefore, we propose that Random Forest machine learning may be optimal for objective assessment of sedentary behaviour and physical activity in older adults using thigh-mounted triaxial accelerometry.

Performance of thigh-mounted triaxial accelerometer algorithms in objective quantification of sedentary behaviour and physical activity in older adults

PubMed Central

Verschueren, Sabine M. P.; Degens, Hans; Morse, Christopher I.; Onambélé, Gladys L.

2017-01-01

Accurate monitoring of sedentary behaviour and physical activity is key to investigate their exact role in healthy ageing. To date, accelerometers using cut-off point models are most preferred for this, however, machine learning seems a highly promising future alternative. Hence, the current study compared between cut-off point and machine learning algorithms, for optimal quantification of sedentary behaviour and physical activity intensities in the elderly. Thus, in a heterogeneous sample of forty participants (aged ≥60 years, 50% female) energy expenditure during laboratory-based activities (ranging from sedentary behaviour through to moderate-to-vigorous physical activity) was estimated by indirect calorimetry, whilst wearing triaxial thigh-mounted accelerometers. Three cut-off point algorithms and a Random Forest machine learning model were developed and cross-validated using the collected data. Detailed analyses were performed to check algorithm robustness, and examine and benchmark both overall and participant-specific balanced accuracies. This revealed that the four models can at least be used to confidently monitor sedentary behaviour and moderate-to-vigorous physical activity. Nevertheless, the machine learning algorithm outperformed the cut-off point models by being robust for all individual’s physiological and non-physiological characteristics and showing more performance of an acceptable level over the whole range of physical activity intensities. Therefore, we propose that Random Forest machine learning may be optimal for objective assessment of sedentary behaviour and physical activity in older adults using thigh-mounted triaxial accelerometry. PMID:29155839

Effects of diet, packaging, and irradiation on protein oxidation, lipid oxidation, and color of raw broiler thigh meat during refrigerated storage.

PubMed

Xiao, S; Zhang, W G; Lee, E J; Ma, C W; Ahn, D U

2011-06-01

This study was designed to evaluate the effects of dietary treatment, packaging, and irradiation singly or in combination on the oxidative stability of broiler chicken thigh meat. A total of 120 four-week-old chickens were divided into 12 pens (10 birds/pen), and 4 pens of broilers were randomly assigned to a control oxidized diet (5% oxidized oil) or an antioxidant-added diet [500 IU of vitamin E + 200 mg/kg of butylated hydroxyanisole (BHA)] and fed for 2 wk. After slaughter, thigh meats were separated, ground, packaged in either oxygen-permeable or oxygen-impermeable vacuum bags, and irradiated at 0 or 3 kGy. Lipid oxidation (TBA-reactive substances), protein oxidation (carbonyl), and color of the meat were measured at 1, 4, and 7 d of refrigerated storage. The lipid and protein oxidation of thigh meats from birds fed the diet supplemented with antioxidants (vitamin E + BHA) was significantly lower than the lipid and protein oxidation of birds fed the control diet, whereas the lipid and protein oxidation of broilers fed the oxidized oil diet was higher than that of birds fed the control diet. Vacuum packaging slowed, but irradiation accelerated, the lipid and protein oxidation of thigh meat during storage. Dietary antioxidants (vitamin E + BHA) and irradiation treatments showed a stronger effect on lipid oxidation than on protein oxidation. A significant correlation between lipid and protein oxidation in meat was found during storage. Dietary supplementation of vitamin E + BHA and the irradiation treatment increased the lightness and redness of thigh meat, respectively. It is suggested that appropriate use of dietary antioxidants in combination with packaging could be effective in minimizing oxidative changes in irradiated raw chicken thigh meat.

Return to play after thigh muscle injury in elite football players: implementation and validation of the Munich muscle injury classification

PubMed Central

Ekstrand, Jan; Askling, Carl; Magnusson, Henrik; Mithoefer, Kai

2013-01-01

Background Owing to the complexity and heterogeneity of muscle injuries, a generally accepted classification system is still lacking. Aims To prospectively implement and validate a novel muscle injury classification and to evaluate its predictive value for return to professional football. Methods The recently described Munich muscle injury classification was prospectively evaluated in 31 European professional male football teams during the 2011/2012 season. Thigh muscle injury types were recorded by team medical staff and correlated to individual player exposure and resultant time-loss. Results In total, 393 thigh muscle injuries occurred. The muscle classification system was well received with a 100% response rate. Two-thirds of thigh muscle injuries were classified as structural and were associated with longer lay-off times compared to functional muscle disorders (p<0.001). Significant differences were observed between structural injury subgroups (minor partial, moderate partial and complete injuries) with increasing lay-off time associated with more severe structural injury. Median lay-off time of functional disorders was 5–8 days without significant differences between subgroups. There was no significant difference in the absence time between anterior and posterior thigh injuries. Conclusions The Munich muscle classification demonstrates a positive prognostic validity for return to play after thigh muscle injury in professional male football players. Structural injuries are associated with longer average lay-off times than functional muscle disorders. Subclassification of structural injuries correlates with return to play, while subgrouping of functional disorders shows less prognostic relevance. Functional disorders are often underestimated clinically and require further systematic study. PMID:23645834

Imaging vascular endothelial growth factor (VEGF) receptors in turpentine-induced sterile thigh abscesses with radiolabeled single-chain VEGF.

PubMed

Levashova, Zoia; Backer, Marina; Backer, Joseph M; Blankenberg, Francis G

2009-12-01

Angiogenesis plays a central role in the pathogenesis of chronic inflammatory disorders. Vascular endothelial growth factor (VEGF) and its receptors are the most important regulators of angiogenesis. We wished to determine whether labeled forms of single-chain VEGF (scVEGF) could be used to image VEGF receptors in a well-characterized model of sterile soft-tissue inflammation induced by intramuscular injection of turpentine. Anesthetized adult male Swiss-Webster mice received a 20-microL intramuscular injection of turpentine into the right thigh. At 4, 7, or 10 d later, groups of 3-5 mice were injected via the tail vein with 50 microg of either scVEGF that had been site specifically labeled with Cy5.5 (scVEGF/Cy) or inactivated scVEGF/Cy (inVEGF/Cy) and then examined by fluorescence imaging. At 3, 4, 6, 7, 9, 10, or 12 d, additional groups of 3-5 mice were injected via the tail vein with 74-111 MBq of (99m)Tc-scVEGF (or (99m)Tc-inVEGF) and then examined by SPECT imaging. On days 3 through 10, both forms of scVEGF (scVEGF/Cy and (99m)Tc-scVEGF) showed significantly higher uptake (P < 0.05) in the right (abscessed) thigh than in the contralateral thigh (and higher uptake than the inactivated tracer). Peak uptake occurred on day 7 (3.67 +/- 1.79 [ratio of uptake in abscessed thigh to uptake in normal thigh, mean +/- SD] and 0.72 +/- 0.01 for scVEGF/Cy and inVEGF/Cy, respectively, and 3.49 +/- 1.22 and 1.04 +/- 0.41 for (99m)Tc-scVEGF and (99m)Tc-inVEGF, respectively) and slowly decreased thereafter. Autoradiography revealed peak tracer uptake in the thick irregular angiogenic rim of the abscess cavity on day 9 (5.83 x 10(-7) +/- 9.22 x 10(-8) and 5.85 x 10(-8) +/- 5.95 x 10(-8) percentage injected dose per pixel for (99m)Tc-scVEGF and (99m)Tc-inVEGF, respectively); in comparison, a thin circumscribed rim of uptake was seen with (99m)Tc-inVEGF. Immunostaining revealed that VEGFR-2 (VEGF receptor) colocalized with CD31 (endothelial cell marker) at all time points in the

Effects of thigh holster use on kinematics and kinetics of active duty police officers.

PubMed

Larsen, Louise Bæk; Tranberg, Roy; Ramstrand, Nerrolyn

2016-08-01

Body armour, duty belts and belt mounted holsters are standard equipment used by the Swedish police and have been shown to affect performance of police specific tasks, to decrease mobility and to potentially influence back pain. This study aimed to investigate the effects on gait kinematics and kinetics associated with use of an alternate load carriage system incorporating a thigh holster. Kinematic, kinetic and temporospatial data were collected using three dimensional gait analysis. Walking tests were conducted with nineteen active duty police officers under three different load carriage conditions: a) body armour and duty belt, b) load bearing vest, body armour and thigh holster and c) no equipment (control). No significant differences between testing conditions were found for temporospatial parameters. Range of trunk rotation was reduced for both load carriage conditions compared to the control condition (p<0.017). Range of hip rotation was more similar to the control condition when wearing thigh holster rather than the belt mounted hip holster (p<0.017). Moments and powers for both left and right ankles were significantly greater for both of the load carriage conditions compared to the control condition (p<0.017). This study confirms that occupational loads carried by police have a significant effect on gait kinematics and kinetics. Although small differences were observed between the two load carriage conditions investigated in this study, results do not overwhelmingly support selection of one design over the other. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparison of the autoregulatory mechanisms between middle cerebral artery and ophthalmic artery after thigh cuff deflation in healthy subjects.

PubMed

Kolodjaschna, Julia; Berisha, Fatmire; Lung, Solveig; Schima, Heinrich; Polska, Elzbieta; Schmetterer, Leopold

2005-02-01

To compare dynamic autoregulation in the middle cerebral artery (MCA) and the ophthalmic artery (OA) after a step decrease in systemic blood pressure. Eighteen healthy male young subjects were studied. Ultrasound parameters and systemic blood pressures were recorded in each subject before, during, and after a step decrease in blood pressure. Continuous blood pressure recordings were made with a finger plethysmograph system, and flow velocities in the MCA and the OA were continuously measured with Doppler ultrasound. Large bilateral thigh cuffs were inflated and a pressure approximately 20 mm Hg above peak systolic blood pressure was maintained for 3 minutes. A decrease in blood pressure was induced by rapid deflation of bilateral thigh cuffs. Experiments were performed separately for the OA and the MCA. Systemic blood pressure showed a step decrease immediately after thigh cuff release (9%-15%) and returned to baseline 7 to 10 pulse cycles later. Flow velocities in the MCA returned to baseline earlier than systemic blood pressure, indicating peripheral vasodilatation, with a maximum of five to six pulse cycles after the blood pressure decrease. By contrast, flow velocities in the OA returned to baseline later than systemic blood pressure, reflecting peripheral vasoconstriction with a maximum 10 to 15 pulse cycles after cuff release. There was a statistically significant difference in the time course of the resistance changes in the two selected arteries after thigh cuff release (P < 0.001). The results of the present study suggest substantial differences in the autoregulatory behavior of the vascular beds peripheral to the MCA and the OA. Results in the MCA would be compatible with either metabolic or myogenic vasodilatation, whereas the results in the OA could reflect sympathetic vasoconstriction. Further studies are needed to support this hypothesis. The thigh cuff technique may represent an interesting approach to the study of autoregulation in patients with

A Simple Model to Identify Risk of Sarcopenia and Physical Disability in HIV-Infected Patients.

PubMed

Farinatti, Paulo; Paes, Lorena; Harris, Elizabeth A; Lopes, Gabriella O; Borges, Juliana P

2017-09-01

Farinatti, P, Paes, L, Harris, EA, Lopes, GO, and Borges, JP. A simple model to identify risk of sarcopenia and physical disability in HIV-infected patients. J Strength Cond Res 31(9): 2542-2551, 2017-Early detection of sarcopenia might help preventing muscle loss and disability in HIV-infected patients. This study proposed a model for estimating appendicular skeletal muscle mass (ASM) to calculate indices to identify "sarcopenia" (SA) and "risk for disability due to sarcopenia" (RSA) in patients with HIV. An equation to estimate ASM was developed in 56 patients (47.2 ± 6.9 years), with a cross-validation sample of 24 patients (48.1 ± 6.6 years). The model validity was determined by calculating, in both samples: (a) Concordance between actual vs. estimated ASM; (b) Correlations between actual/estimated ASM vs. peak torque (PT) and total work (TW) during isokinetic knee extension/flexion; (c) Agreement of patients classified with SA and RSA. The predictive equation was ASM (kg) = 7.77 (sex; F = 0/M = 1) + 0.26 (arm circumference; cm) + 0.38 (thigh circumference; cm) + 0.03 (Body Mass Index; kg·m) - 8.94 (R = 0.74; Radj = 0.72; SEE = 3.13 kg). Agreement between actual vs. estimated ASM was confirmed in validation (t = 0.081/p = 0.94; R = 0.86/p < 0.0001) and cross-validation (t = 0.12/p = 0.92; R = 0.87/p < 0.0001) samples. Regression characteristics in cross-validation sample (Radj = 0.80; SEE = 3.65) and PRESS (RPRESS = 0.69; SEEPRESS = 3.35) were compatible with the original model. Percent agreements for the classification of SA and RSA from indices calculated using actual and estimated ASM were of 87.5% and 77.2% (gamma correlations 0.72-1.0; p < 0.04) in validation, and 95.8% and 75.0% (gamma correlations 0.98-0.97; p < 0.001) in cross-validation sample, respectively. Correlations between actual/estimated ASM vs. PT (range 0.50-0.73, p ≤ 0.05) and TW (range 0.59-0.74, p ≤ 0.05) were similar in both samples. In conclusion, our model correctly estimated ASM

Towards multiscale modeling of influenza infection

PubMed Central

Murillo, Lisa N.; Murillo, Michael S.; Perelson, Alan S.

2013-01-01

Aided by recent advances in computational power, algorithms, and higher fidelity data, increasingly detailed theoretical models of infection with influenza A virus are being developed. We review single scale models as they describe influenza infection from intracellular to global scales, and, in particular, we consider those models that capture details specific to influenza and can be used to link different scales. We discuss the few multiscale models of influenza infection that have been developed in this emerging field. In addition to discussing modeling approaches, we also survey biological data on influenza infection and transmission that is relevant for constructing influenza infection models. We envision that, in the future, multiscale models that capitalize on technical advances in experimental biology and high performance computing could be used to describe the large spatial scale epidemiology of influenza infection, evolution of the virus, and transmission between hosts more accurately. PMID:23608630

Sex- and age-related differences in mid-thigh composition and muscle quality determined by computed tomography in middle-aged and elderly Japanese.

PubMed

Kasai, Takehiro; Ishiguro, Naoki; Matsui, Yasumoto; Harada, Atsushi; Takemura, Marie; Yuki, Atsumu; Kato, Yuki; Otsuka, Rei; Ando, Fujiko; Shimokata, Hiroshi

2015-06-01

Sex- and age-related differences in mid-thigh composition and muscle quality remain unclear. The present study aimed to clarify these differences using computed tomography in middle-aged and elderly Japanese. A total of 2310 participants (age 40-89 years), who were randomly selected from the local residents, underwent computed tomography examination of the right mid-thigh. Thigh circumference and cross-sectional areas of the thigh, muscle, quadriceps, non-quadriceps, fat, and bone were measured. Knee extension strength and muscle quality index (knee extension strength/quadriceps cross-sectional area) were also assessed. Sex- and age-related differences in these indices were analyzed. The thigh cross-sectional area in men and women decreased by 0.6% and 0.5%/year, respectively, because of a decrease in muscle cross-sectional area (men 75.2%, women 40.6%), fat cross-sectional area (men 24.4%, women 59.6%) and bone cross-sectional area (men 0.5%, women -0.2%). Muscle cross-sectional area in men and women decreased by 0.6% and 0.4%/year, respectively, because of a decrease in quadriceps cross-sectional area (men 65.6%, women 81.6%) and non-quadriceps cross-sectional area (men 34.4%, women 18.4%). Muscle quality in men and women decreased by 0.4% and 0.3%/year, respectively. Thigh cross-sectional area decreased with age mainly because of a decrease in muscle cross-sectional area in men and fat cross-sectional area in women. The rate of decrease in muscle cross-sectional area was 1.5-fold higher in men than in women. Muscle cross-sectional area decreased with age mainly because of a decrease in quadriceps cross-sectional area, especially in women. Decrease in muscle quality with age was similar in both sexes. © 2014 Japan Geriatrics Society.

The posterior thigh flap for defect coverage of ischial pressure sores - a critical single-centre analysis.

PubMed

Djedovic, Gabriel; Morandi, Evi M; Metzler, Julia; Wirthmann, Anna; Matiasek, Johannes; Bauer, Thomas; Rieger, Ulrich M

2017-12-01

The development of pressure sores is still not only an enormous economical but also a medical burden. Especially in the ischial region, the local defect coverage remains demanding as it is the main weight-bearing area in wheelchair-mobilised patients and is prone to high mobility. The purpose of our study was to report our long-time experience with the reconstruction of ischial pressure ulcers with the medially based posterior thigh flap. A retrospective analysis of all primary pressure sores grade III-IV in the ischial area, which were covered with a medially based posterior thigh flap between January 2008 and December 2014, at our department was conducted. A total of 28 patients underwent defect coverage of an ischial pressure sore with the aforementioned flap. The subgroup with complications showed a statistically significant longer hospital stay. A statistically significant correlation between age and the coincidence of comorbidities could be seen. Older patients showed significantly higher grades of pressure sores. The medially based posterior thigh flap is a safe and reliable flap design. Complication rates are comparable to other flaps. Nevertheless, in case of complications, a significantly longer duration of hospitalisation has to be taken into account. © 2017 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Varicella infection modeling.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jones, Katherine A.; Finley, Patrick D.; Moore, Thomas W.

2013-09-01

Infectious diseases can spread rapidly through healthcare facilities, resulting in widespread illness among vulnerable patients. Computational models of disease spread are useful for evaluating mitigation strategies under different scenarios. This report describes two infectious disease models built for the US Department of Veteran Affairs (VA) motivated by a Varicella outbreak in a VA facility. The first model simulates disease spread within a notional contact network representing staff and patients. Several interventions, along with initial infection counts and intervention delay, were evaluated for effectiveness at preventing disease spread. The second model adds staff categories, location, scheduling, and variable contact rates tomore » improve resolution. This model achieved more accurate infection counts and enabled a more rigorous evaluation of comparative effectiveness of interventions.« less

Scaling and the frequency dependence of Nyquist plot maxima of the electrical impedance of the human thigh.

PubMed

Shiffman, Carl

2017-11-30

To define and elucidate the properties of reduced-variable Nyquist plots. Non-invasive measurements of the electrical impedance of the human thigh. A retrospective analysis of the electrical impedances of 154 normal subjects measured over the past decade shows that 'scaling' of the Nyquist plots for human thigh muscles is a property shared by healthy thigh musculature, irrespective of subject and the length of muscle segment. Here the term scaling signifies the near and sometimes 'perfect' coalescence of the separate X versus R plots into one 'reduced' Nyquist plot by the simple expedient of dividing R and X by X m , the value of X at the reactance maximum. To the extent allowed by noise levels one can say that there is one 'universal' reduced Nyquist plot for the thigh musculature of healthy subjects. There is one feature of the Nyquist curves which is not 'universal', however, namely the frequency f m at which the maximum in X is observed. That is found to vary from 10 to 100 kHz. depending on subject and segment length. Analysis shows, however, that the mean value of 1/f m is an accurately linear function of segment length, though there is a small subject-to-subject random element as well. Also, following the recovery of an otherwise healthy victim of ankle fracture demonstrates the clear superiority of measurements above about 800 kHz, where scaling is not observed, in contrast to measurements below about 400 kHz, where scaling is accurately obeyed. The ubiquity of 'scaling' casts new light on the interpretation of impedance results as they are used in electrical impedance myography and bioelectric impedance analysis.

Finite element analysis to investigate variability of MR elastography in the human thigh.

PubMed

Hollis, L; Barnhill, E; Perrins, M; Kennedy, P; Conlisk, N; Brown, C; Hoskins, P R; Pankaj, P; Roberts, N

2017-11-01

To develop finite element analysis (FEA) of magnetic resonance elastography (MRE) in the human thigh and investigate inter-individual variability of measurement of muscle mechanical properties. Segmentation was performed on MRI datasets of the human thigh from 5 individuals and FEA models consisting of 12 muscles and surrounding tissue created. The same material properties were applied to each tissue type and a previously developed transient FEA method of simulating MRE using Abaqus was performed at 4 frequencies. Synthetic noise was applied to the simulated data at various levels before inversion was performed using the Elastography Software Pipeline. Maps of material properties were created and visually assessed to determine key features. The coefficient of variation (CoV) was used to assess the variability of measurements in each individual muscle and in the groups of muscles across the subjects. Mean measurements for the set of muscles were ranked in size order and compared with the expected ranking. At noise levels of 2% the CoV in measurements of |G * | ranged from 5.3 to 21.9% and from 7.1 to 36.1% for measurements of ϕ in the individual muscles. A positive correlation (R 2 value 0.80) was attained when the expected and measured |G * | ranking were compared, whilst a negative correlation (R 2 value 0.43) was found for ϕ. Created elastograms demonstrated good definition of muscle structure and were robust to noise. Variability of measurements across the 5 subjects was dramatically lower for |G * | than it was for ϕ. This large variability in ϕ measurements was attributed to artefacts. Copyright © 2017 Elsevier Inc. All rights reserved.

The effectiveness and safety of topical PhotoActif phosphatidylcholine-based anti-cellulite gel and LED (red and near-infrared) light on Grade II-III thigh cellulite: a randomized, double-blinded study.

PubMed

Sasaki, Gordon H; Oberg, Kerby; Tucker, Barbara; Gaston, Margaret

2007-06-01

Cellulite of the upper lateral and posterior thighs and lower buttocks represents a common, physiological and unwanted condition whose etiologies and effective management are subjects of continued debate. The purpose of this controlled, double-blinded study is to evaluate the efficacy and safety of a novel phosphatidylcholine-based, cosmeceutical anti-cellulite gel combined with a light-emitting diode (LED) array at the wavelengths of red (660 nm) and near-infrared (950 nm), designed to counter the possible mechanisms that purportedly accentuate the presence of thigh cellulite. Nine healthy female volunteers with Grade II-III thigh cellulite were randomly treated twice daily with an active gel on one thigh and a placebo gel on the control thigh for 3 months. Twice weekly, each thigh was exposed for a 15-minute treatment with LED light for a total of 24 treatments. At 0, 6, and 12 weeks of the study the following clinical determinants were obtained: standardized digital photography, height and weight measurements, standardized thigh circumference tape measurements, pinch testing, body mass index (kg/m2), body fat analysis (Futrex-5500/XL near-infrared analyzer), and digital high-resolution ultrasound imaging of the dermal-adiposal border. In selected patients, full-thickness biopsies of the placebo and active-treated sites were obtained. At 18 months, repeat standardized digital photography, height and weight measurements, and body mass index measurements were obtained. At the end of 3 months, eight of nine thighs treated with the phosphatidylcholine-based, anti-cellulite gel and LED treatments were downgraded to a lower cellulite grade by clinical examination, digital photography, and pinch test assessment. Digital ultrasound at the dermal-adiposal interface demonstrated not only a statistically significant reduction of immediate hypodermal depth, but also less echo-like intrusions into the dermal layer. Three of six biopsies from thighs treated for 3 months with

Evaluation of the relation between triceps surae H-reflex, M-response latencies and thigh length in normal population.

PubMed

Khosrawi, Saeid; Fallah, Salman

2013-03-01

The H-reflex is a useful electrophysiological procedure for evaluating the status of the peripheral nervous system, especially at the proximal segment of the peripheral nerve. The purpose of this study is to investigate the relation between triceps surae H-reflex and M- response latencies and thigh length in normal population, in order to determine if there is any regression equation between them. After screening 75 volunteers by considering inclusion and exclusion criteria, 72 of them were selected to enroll into our study (34 men and 38 women with the mean age of 36.04 ± 7.7 years). In all of the subjects H-reflex and M-response latencies were recorded by standard electrophysiological techniques and thigh length was measured. Finally, our data was analyzed for its relations with respect to ages in both sexes by appropriate statistical and mathematical methods. Mean ± SD for H-reflex latency was 27.94 ± 1.6 ms. We found a significant correlation between H-reflex latency and M-latency (r = 0.28), no significant correlation was found between H-reflex latency and thigh length (r = -0.051). Finally based on our findings we introduce a new formula in this paper. We found a significant correlation among of M-response latency and other variables (H-reflex latency and thigh length). Despite this it was eliminated from our formula. The relationship between H-reflex latency and age was significant. Further studies are required to delineate the clinical usage and interpretation of the formula, which we found in this study.

Compartment syndrome as a complication of a stab wound to the thigh: a case report and review of the literature

PubMed Central

Gillooly, John J; Hacker, Andrew; Patel, Vipul

2007-01-01

Acute compartment syndrome of the thigh is a rare but potentially devastating condition, in which the pressure within the osseofascial compartment rises above the capillary perfusion gradient, leading to cellular anoxia, muscle ischaemia and death. Early diagnosis and treatment is essential to prevent long term disability. It is most often associated with crush injuries and femoral fracture. We present a previously unreported case of thigh compartment syndrome following a stab injury, treated by emergent fasciotomy. PMID:17954836

Infestation of the spur-thighed tortoise (Testudo graeca) by Hyalomma aegyptium in Tunisia.

PubMed

Gharbi, Mohamed; Rjeibi, Mohamed Ridha; Rouatbi, Mariem; Mabrouk, Moez; Mhadhbi, Moez; Amairia, Safa; Amdouni, Yosra; Boussaadoun, Mohamed Anis

2015-04-01

We examined 210 spur-thighed tortoises (Testudo graeca) for the presence of ticks in Tunisia during May 2014. A total number of 602 adult ticks were collected and identified leading to the estimation of parasitological indicators. All the ticks belonged to a single species: Hyalomma aegyptium. The mean infestation prevalence was 66.2%, mean overall infestation intensity and abundance were 4.33 and 2.86 ticks/tortoise respectively. Our survey showed that tortoises were significantly more infested by male ticks than females (p<0.001). The ticks were mainly present in the posterior limbs compared to other body regions (p<0.05). There was no significance variation of length and weight of tortoises according to sex (p<0.05). There was a significant correlation between the tortoises' size (length and weight) and tick infestation. This study showed high tick burdens of spur-thighed tortoises in Tunisia; further investigations are needed to determine exactly the role of this tick species in the transmission of different zoonotic pathogens. Copyright © 2015 Elsevier GmbH. All rights reserved.

Acute Effects of Lateral Thigh Foam Rolling on Arterial Tissue Perfusion Determined by Spectral Doppler and Power Doppler Ultrasound.

PubMed

Hotfiel, Thilo; Swoboda, Bernd; Krinner, Sebastian; Grim, Casper; Engelhardt, Martin; Uder, Michael; Heiss, Rafael U

2017-04-01

Hotfiel, T, Swoboda, B, Krinner, S, Grim, C, Engelhardt, M, Uder, M, and Heiss, R. Acute effects of lateral thigh foam rolling on arterial tissue perfusion determined by spectral Doppler and power Doppler ultrasound. J Strength Cond Res 31(4): 893-900, 2017-Foam rolling has been developed as a popular intervention in training and rehabilitation. However, evidence on its effects on the cellular and physiological level is lacking. The aim of this study was to assess the effect of foam rolling on arterial blood flow of the lateral thigh. Twenty-one healthy participants (age, 25 ± 2 years; height, 177 ± 9 cm; body weight, 74 ± 9 kg) were recruited from the medical and sports faculty. Arterial tissue perfusion was determined by spectral Doppler and power Doppler ultrasound, represented as peak flow (Vmax), time average velocity maximum (TAMx), time average velocity mean (TAMn), and resistive index (RI), and with semiquantitative grading that was assessed by 4 blindfolded investigators. Measurement values were assessed under resting conditions and twice after foam rolling exercises of the lateral thigh (0 and 30 minutes after intervention). The trochanteric region, mid portion, and distal tibial insertion of the lateral thigh were representative for data analysis. Arterial blood flow of the lateral thigh increased significantly after foam rolling exercises compared with baseline (p ≤ 0.05). We detected a relative increase in Vmax of 73.6% (0 minutes) and 52.7% (30 minutes) (p < 0.001), in TAMx of 53.2% (p < 0.001) and 38.3% (p = 0.002), and in TAMn of 84.4% (p < 0.001) and 68.2% (p < 0.001). Semiquantitative power Doppler scores at all portions revealed increased average grading of 1.96 after intervention and 2.04 after 30 minutes compared with 0.75 at baseline. Our results may contribute to the understanding of local physiological reactions to self-myofascial release.

Evaluation of enzymatically treated Artemisia annua L. on growth performance, meat quality, and oxidative stability of breast and thigh muscles in broilers.

PubMed

Wan, X L; Song, Z H; Niu, Y; Cheng, K; Zhang, J F; Ahmad, H; Zhang, L L; Wang, T

2017-04-01

An experiment was conducted to evaluate the effects of including enzymatically treated Artemisia annua L. (EA) in broiler diets on growth performance, meat quality, and oxidative stability of breast and thigh muscles. A total of 256 one-d-old Arbor Acres broiler chicks were randomly allotted into four groups with eight replicates of eight birds each. Broilers in the four groups were offered basal diet supplemented with 0.0, 0.5, 1.0, and 1.5 g/kg EA during the 42-d experiment, respectively. The ADG, ADFI, and feed/gain ratio (F:G) were measured at 42 d of age. Breast and thigh muscle samples from eight birds per treatment were obtained at 42 d to determine meat quality, free radical scavenging activity, and lipid peroxidation. All treatment groups had similar ADG, ADFI, and F:G during the 42 d experiment (P > 0.05). Drip loss at 24 h and shearing force of breast muscle were linearly (P < 0.05) and quadratically (P < 0.05) decreased by EA addition. The drip loss at 24 h and 48 h, cooking loss and shearing force of thigh muscle followed the same fashion. The supplementation of EA quadratically increased 2, 2-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS) (P = 0.004) and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) (P = 0.035) free radical scavenging activities in breast muscle, and linearly (P < 0.05) and quadratically (P < 0.05) increased ABTS and DPPH scavenging activities of thigh muscle. Increasing levels of EA linearly (P < 0.05) or quadratically (P < 0.05) or both decreased the malondialdehyde (MDA) concentrations in breast and thigh muscle samples during 15 d of storage at 4°C. The results indicated that EA supplementation improved meat quality and oxidative stability of breast and thigh muscles in broilers. The inclusion level of 1.0 g/kg EA in broiler diet was recommended. © 2016 Poultry Science Association Inc.

Effect of sensory training of the posterior thigh on trunk control and upper extremity functions in stroke patients.

PubMed

Dogru Huzmeli, Esra; Yildirim, Sibel Aksu; Kilinc, Muhammed

2017-04-01

Some studies show that sensorial rehabilitation is effective on functionality. The aim of this study is to investigate the effect of sensory training of the posterior thigh on the functionality of upper extremity and trunk control in stroke patients. Thirteen subjects (53.23 ± 6.82 years) were included in the intervention group and 13 subjects (58.69 ± 5.94 years) in the control group. The control and intervention groups were treated for ten sessions. The control group was treated only with neurodevelopmental treatment, and the intervention group was treated with sensorial training on the posterior thigh in addition to the neurodevelopmental treatment. Subjects were evaluated three times, pre- and post-treatment and 10 days after finishing the treatment. Trunk control was assessed by the Trunk Impairment Scale, reaching function by the Functional Reach Test, balance by the Berg Balance Test, upper extremity symptom and disability severity by the Disabilities of the Arm, Shoulder, Hand and Minnesota, independence level in daily living activities by the Barthel Index, and sensory function of the posterior thigh by sensorial tests. In the post-treatment assessment, it was found that the intervention group was better than the control group in the parameter of functional reach while sitting (p < 0.005). In the third assessment, reaching while sitting and independence level were better in the intervention group than the control group (p < 0.005). There was no difference in sensorial assessment between the groups. Sensory training of the posterior thigh should be included in the rehabilitation programme of stroke patients.

Spatial genetic structure of bristle-thighed curlews (Numenius tahitiensis): breeding area differentiation not reflected on the non-breeding grounds

USGS Publications Warehouse

Sonsthagen, Sarah A.; Tibbitts, T. Lee; Gill, Robert E.; Williams, Ian S.; Talbot, Sandra L.

2015-01-01

Migratory birds occupy geographically and ecologically disparate areas during their annual cycle with conditions on breeding and non-breeding grounds playing separate and important roles in population dynamics. We used data from nuclear microsatellite and mitochondrial DNA control region loci to assess the breeding and non-breeding spatial genetic structure of a transoceanic migrant shorebird, the bristle-thighed curlew. We found spatial variance in the distribution of allelic and haplotypic frequencies between the curlew's two breeding areas in Alaska but did not observe this spatial structure throughout its non-breeding range on low-lying tropical and subtropical islands in the Central Pacific (Oceania). This suggests that the two breeding populations do not spatially segregate during the non-breeding season. Lack of migratory connectivity is likely attributable to the species' behavior, as bristle-thighed curlews exhibit differential timing of migration and some individuals move among islands during non-breeding months. Given the detrimental impact of many past and current human activities on island ecosystems, admixture of breeding populations in Oceania may render the bristle-thighed curlew less vulnerable to perturbations there, as neither breeding population will be disproportionally affected by local habitat losses or by stochastic events. Furthermore, lack of migratory connectivity may enable bristle-thighed curlews to respond to changing island ecosystems by altering their non-breeding distribution. However, availability of suitable non-breeding habitat for curlews in Oceania is increasingly limited on both low-lying and high islands by habitat loss, sea level rise, and invasive mammalian predators that pose a threat to flightless and flight-compromised curlews during the molting period.

Effects of post-fracture non-weight-bearing immobilization on muscle atrophy, intramuscular and intermuscular adipose tissues in the thigh and calf.

PubMed

Yoshiko, Akito; Yamauchi, Koun; Kato, Takayuki; Ishida, Koji; Koike, Teruhiko; Oshida, Yoshiharu; Akima, Hiroshi

2018-06-09

Disuse and/or a non-weight-bearing condition changes muscle composition, with decreased skeletal muscle tissue and increased fat within (intramuscular adipose tissue, IntraMAT) and between (intermuscular adipose tissue, InterMAT) given muscles. Excessive adipose tissue contributes to dysfunctional and metabolically impaired muscle. How these adipose tissues change during orthopedic treatment (e.g., cast immobilization, daily use of crutches) is not well documented. This study aimed to quantify changes in IntraMAT, InterMAT, and thigh and calf muscle tissue during orthopedic treatment. We studied 8 patients with fifth metatarsal bone or fibular fractures. The ankle joint involved underwent plaster casting for approximately 4 weeks, with crutches used during that time. Axial T1-weighted MRI at the mid-thigh and a 30% proximal site at the calf were obtained to measure IntraMAT and InterMAT cross-sectional areas (CSAs) and skeletal muscle tissue CSA before treatment and 4 weeks afterward. Thigh and calf muscle tissue CSAs were significantly decreased from before to after treatment: thigh, 85.8 ± 7.6 to 77.1 ± 7.3 cm 2 ; calf, 53.3 ± 5.5 to 48.9 ± 5.0 cm 2 (p < 0.05). None of the IntraMAT or InterMAT changes was statistically significant. There was a relation between the percentage change of thigh IntraMAT CSA and muscle tissue CSA (r s  = -0.86, p < 0.01). The 4 weeks of treatment primarily induced skeletal muscle atrophy with less of an effect on IntraMAT or InterMAT. There is a risk of increasing IntraMAT relatively by decreasing skeletal muscle tissue size during orthopedic treatment.

The influence of changes in trunk and pelvic posture during single leg standing on hip and thigh muscle activation in a pain free population.

PubMed

Prior, Simon; Mitchell, Tim; Whiteley, Rod; O'Sullivan, Peter; Williams, Benjamin K; Racinais, Sebastien; Farooq, Abdulaziz

2014-03-27

Thigh muscle injuries commonly occur during single leg loading tasks and patterns of muscle activation are thought to contribute to these injuries. The influence trunk and pelvis posture has on hip and thigh muscle activation during single leg stance is unknown and was investigated in a pain free population to determine if changes in body posture result in consistent patterns of changes in muscle activation. Hip and thigh muscle activation patterns were compared in 22 asymptomatic, male subjects (20-45 years old) in paired functionally relevant single leg standing test postures: Anterior vs. Posterior Trunk Sway; Anterior vs. Posterior Pelvic Rotation; Left vs. Right Trunk Shift; and Pelvic Drop vs. Raise. Surface EMG was collected from eight hip and thigh muscles calculating Root Mean Square. EMG was normalized to an "upright standing" reference posture. Repeated measures ANOVA was performed along with associated F tests to determine if there were significant differences in muscle activation between paired test postures. In right leg stance, Anterior Trunk Sway (compared to Posterior Sway) increased activity in posterior sagittal plane muscles, with a concurrent deactivation of anterior sagittal plane muscles (p: 0.016 - <0.001). Lateral hip abductor muscles increased activation during Left Trunk Shift (compared to Right) (p :≤ 0.001). Lateral Pelvic Drop (compared to Raise) decreased activity in hip abductors and increased hamstring, adductor longus and vastus lateralis activity (p: 0.037 - <0.001). Changes in both trunk and pelvic posture during single leg stance generally resulted in large, predictable changes in hip and thigh muscle activation in asymptomatic young males. Changes in trunk position in the sagittal plane and pelvis position in the frontal plane had the greatest effect on muscle activation. Investigation of these activation patterns in clinical populations such as hip and thigh muscle injuries may provide important insights into injury

Morphometric analysis of high-intensity focused ultrasound-induced lipolysis on cadaveric abdominal and thigh skin.

PubMed

Lee, Sugun; Kim, Hee-Jin; Park, Hyun Jun; Kim, Hyoung Moon; Lee, So Hyun; Cho, Sung Bin

2017-07-01

Non-focused ultrasound and high-intensity focused ultrasound (HIFU) devices induce lipolysis by generating acoustic cavitation and coagulation necrosis in targeted tissues. We aimed to investigate the morphometric characteristics of immediate tissue reactions induced by 2 MHz, 13-mm focused HIFU via two-dimensional ultrasound images and histologic evaluation of cadaveric skin from the abdomen and thigh. Acoustic fields of a 2 MHz, 38-mm HIFU transducer were characterized by reconstruction of the fields using acoustic intensity measurement. Additionally, abdominal and thigh tissues from a fresh cadaver were treated with a HIFU device for a single, two, and three pulses at the pulse energy of 130 J/cm 2 and a penetration depth of 13 mm. Acoustic intensity measurement revealed characteristic focal zones of significant thermal injury at the depth of 38 mm. In both the abdomen and thigh tissue, round to oval ablative thermal injury zones (TIZs) were visualized in subcutaneous fat layers upon treatment with a single pulse of HIFU treatment. Two to three HIFU pulses generated larger and more remarkable ablative zones throughout subcutaneous fat layers. Finally, experimental treatment in a tumescent infiltration-like setting induced larger HIFU-induced TIZs of an oval or columnar shape, compared to non-tumescent settings. Although neither acoustic intensity measurement nor cadaveric tissue exactly reflects in vivo HIFU-induced reactions in human tissue, we believe that our data will help guide further in vivo studies in investigating the therapeutic efficacy and safety of HIFU-induced lipolysis.

Reconstruction With Pedicled Anterolateral Thigh Flap After Wide Local Excision of Penoscrotal Extramammary Paget's Disease: A Case Report and Comprehensive Literature Review

PubMed Central

Skinner, Eila C.; Lee, Gordon K.

2015-01-01

Objective: The clinical characteristics, management, and prognostic indicators of penoscrotal extramammary Paget's disease are not clearly defined. Surgical excision is often an effective treatment modality but results in a large wound after resection of all involved tissues. Methods: Reconstruction of large penoscrotal soft-tissue defects after wide local excision remains a challenge to the reconstructive surgeon. The use of the anterolateral thigh flap for penoscrotal reconstruction after resection of extramammary Paget's disease is infrequent as a reconstruction tool throughout the literature. Results: We discuss a case where the anterolateral thigh flap was effectively used for reconstruction of a large penoscrotal defect after wide local excision of penoscrotal extramammary Paget's disease and present a comprehensive literature review of extramammary Paget's disease key features, diagnosis, prognosis, and treatment. Conclusions: The anterolateral thigh flap is a useful tool for penoscrotal defect reconstruction. PMID:26171098

A novel epidemic spreading model with decreasing infection rate based on infection times

NASA Astrophysics Data System (ADS)

Huang, Yunhan; Ding, Li; Feng, Yun

2016-02-01

A new epidemic spreading model where individuals can be infected repeatedly is proposed in this paper. The infection rate decreases according to the times it has been infected before. This phenomenon may be caused by immunity or heightened alertness of individuals. We introduce a new parameter called decay factor to evaluate the decrease of infection rate. Our model bridges the Susceptible-Infected-Susceptible(SIS) model and the Susceptible-Infected-Recovered(SIR) model by this parameter. The proposed model has been studied by Monte-Carlo numerical simulation. It is found that initial infection rate has greater impact on peak value comparing with decay factor. The effect of decay factor on final density and threshold of outbreak is dominant but weakens significantly when considering birth and death rates. Besides, simulation results show that the influence of birth and death rates on final density is non-monotonic in some circumstances.

Inoculum Effects of Ceftobiprole, Daptomycin, Linezolid, and Vancomycin with Staphylococcus aureus and Streptococcus pneumoniae at Inocula of 105 and 107 CFU Injected into Opposite Thighs of Neutropenic Mice

PubMed Central

Lee, Dong-Gun; Murakami, Yoichi; Andes, David R.

2013-01-01

Reduced bactericidal efficacy at a high inoculum is known as the inoculum effect (IE). We used neutropenic mice to compare the IEs of ceftobiprole (CFB), daptomycin (DAP), linezolid (LZD), and vancomycin (VAN) against 6 to 9 strains of Staphylococcus aureus and 4 strains of Streptococcus pneumoniae at 2 inocula in opposite thighs of the same mice. Neutropenic mice had 104.5 to 105.7 CFU/thigh (low inoculum [LI]) in one thigh and 106.4 to 107.2 CFU/thigh (high inoculum [HI]) in the opposite thigh when treated for 24 h with subcutaneous (s.c.) doses every 12 h of DAP at 0.024 to 100 mg/kg of body weight and LZD at 0.313 to 320 mg/kg and s.c. doses every 6 h of CFB at 0.003 to 160 mg/kg and VAN at 0.049 to 800 mg/kg. Dose-response data were analyzed by a maximum effect (Emax) model using nonlinear regression. Static doses for each drug and at each inoculum were calculated, and the difference between HI and LI (IE index) gave the magnitude of IE for each drug-organism combination. Mean (range) IE indexes of S. aureus were 2.9 (1.7 to 4.6) for CFB, 4.1 (2.6 to 9.3) for DAP, 4.6 (1.7 to 7.1) for LZD, and 10.1 (6.3 to 20.3) for VAN. In S. pneumoniae, the IE indexes were 2.5 (1.3 to 3.3) for CFB, 2.0 (1.6 to 2.8) for DAP, 1.9 (1.7 to 2.2) for LZD, and 1.5 (0.8 to 3.2) for VAN; these values were similar for all drugs. In S. aureus, the IE was much larger with VAN than with CFB, DAM, and LZD (P < 0.05). An in vivo time course of vancomycin activity showed initiation of killing at 4- to 16-fold-higher doses at HI than at LI despite similar initial growth of controls. PMID:23295932

Targeted photodynamic therapy of established soft-tissue infections in mice

NASA Astrophysics Data System (ADS)

Gad, Faten; Zahra, Touqir; Hasan, Tayyaba; Hamblin, Michael R.

2004-06-01

The worldwide rise in antibiotic resistance necessitates the development of novel antimicrobial strategies. Although many workers have used photodynamic therapy (PDT) to kill bacteria in vitro, the use of this approach has seldom been reported in vivo in animal models of infection. We have previously described the first use of PDT to treat excisional wound infections by Gram-negative bacteria in living mice. However these infected wound models used a short time after infection (30 min) before PDT. We now report on the use of PDT to treat an established soft-tissue infection in mice. We used Staphylococcus aureus stably transformed with a Photorhabdus luminescens lux operon (luxABCDE) that was genetically modified to be functional in Gram-positive bacteria. These engineered bacteria emitted bioluminescence allowing the progress of the infection to be monitored in both space and time with a lowlight imaging charged couple device (CCD) camera. One million cells were injected into one or both thigh muscles of mice that had previously been rendered neutropenic by cyclophosphamide administration. Twenty-four hours later the bacteria had multiplied more than one hundred-fold, and poly-L-lysine chlorin(e6) conjugate or free chlorin(e6) was injected into one area of infected muscle and imaged with the CCD camera. Thirty-minutes later red light from a diode laser was delivered as a surface spot or by interstitial fiber into the infection. There was a lightdose dependent loss of bioluminescence (to < 5% of that seen in control infections) not seen in untreated or light alone treated infections, but in some cases the infection recurred. Conjugate alone led to a lesser reduction in bioluminescence. Infections treated with free chlorin(e6) responded less and the infection subsequently increased over the succeeding days, probably due to PDT-mediated tissue damage. PDT-treated infected legs healed better than legs with untreated infections. This data shows that PDT may have

Noninvasive lifting of arm, thigh, and knee skin with transcutaneous intense focused ultrasound.

PubMed

Alster, Tina S; Tanzi, Elizabeth L

2012-05-01

Transcutaneous intense focused ultrasound is a novel Food and Drug Administration-approved technology for noninvasive skin tightening of the face and neck. No studies have reported on its safety and effectiveness on nonfacial areas. Eighteen paired areas (6 each) on the upper arms, medial thighs, and extensor knees were randomly treated with two different transducers (4.0 MHz, 4.5-mm focal depth and 7.0 MHz, 3.0-mm focal depth). One side was randomly assigned to receive a single pass (single plane) of microthermal coagulation zones over the involved area with the 4.0 MHz, 4.5-mm-depth transducer, and the contralateral side was assigned to receive consecutive single passes (dual plane) using both transducers (4.0 MHz, 4.5-mm depth followed by 7.0 MHz, 3.0-mm depth). Two independent masked assessors determined clinical improvement scores using comparative standardized photographs obtained at baseline and 3 and 6 months after treatment. Subjective assessments of clinical improvement and side effects of treatment were obtained. Global assessment scores revealed significant improvement in all treated areas, with the upper arms and knees demonstrating more skin lifting and tightening than the thighs. Areas receiving dual-plane treatment had slightly better clinical scores than those receiving single-plane treatment in all three sites. Clinical scores from single-plane and dual-plane treated areas continued to improve between 3 and 6 months after treatment. Side effects were mild and transient and included erythema, warmth, and skin tenderness. Rare focal bruising was noted in two patients on the upper arms that resolved within 7 days. No other side effects were reported or observed. Transcutaneous intense focused ultrasound can be safely and effectively used to improve the clinical appearance (texture and contour) of the upper arms, extensor knees, and medial thighs. © 2012 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.

Modeling Intraocular Bacterial Infections

PubMed Central

Astley, Roger A.; Coburn, Phillip S.; Parkunan, Salai Madhumathi; Callegan, Michelle C.

2016-01-01

Bacterial endophthalmitis is an infection and inflammation of the posterior segment of the eye which can result in significant loss of visual acuity. Even with prompt antibiotic, anti-inflammatory and surgical intervention, vision and even the eye itself may be lost. For the past century, experimental animal models have been used to examine various aspects of the pathogenesis and pathophysiology of bacterial endophthalmitis, to further the development of anti-inflammatory treatment strategies, and to evaluate the pharmacokinetics and efficacies of antibiotics. Experimental models allow independent control of many parameters of infection and facilitate systematic examination of infection outcomes. While no single animal model perfectly reproduces the human pathology of bacterial endophthalmitis, investigators have successfully used these models to understand the infectious process and the host response, and have provided new information regarding therapeutic options for the treatment of bacterial endophthalmitis. This review highlights experimental animal models of endophthalmitis and correlates this information with the clinical setting. The goal is to identify knowledge gaps that may be addressed in future experimental and clinical studies focused on improvements in the therapeutic preservation of vision during and after this disease. PMID:27154427

Actinomyces gerencseriae hip prosthesis infection: a case report.

PubMed

Dubourg, Grégory; Delord, Marion; Gouriet, Frédérique; Fournier, Pierre-Edouard; Drancourt, Michel

2015-09-28

Actinomyces bacteria are part of the human oropharyngeal microbiota. They have been associated with abdominal, cervicofacial and thoracic infections and a few cases of joint infections have also been described. In particular, Actinomyces gerencseriae, formerly described as Actinomyces israelii serovar II, has rarely been associated with human infections, mostly involving cervicofacial lesions and periodontal diseases. Here, we report one case of hip prosthesis infection due to A. gerencseriae. A 72-year-old Caucasian male developed an inflammatory collection on the outside of the right thigh where a hip prosthesis had been implanted for 11 years. Culturing a fluid sample from the collection puncture found Staphylococcus hominis and a Gram-positive bacillus unidentified by matrix-assisted laser desorption ionization time-of-flight mass-spectrometry (MALDI-TOF). Sequencing the 16S rRNA gene amplified from both the specimen and the isolate identified A. gerencseriae. Treatment adjusted with amoxicillin and trimethropim-sulfamethoxazole cured the infection. The recently described A. gerencseriae has rarely been involved in human infections. We report the first case of A. gerencseriae joint infection in a hip prosthesis.

Imaging Enterobacteriaceae infection in vivo with 18F-fluorodeoxysorbitol positron emission tomography

PubMed Central

Weinstein, Edward A.; Ordonez, Alvaro A.; DeMarco, Vincent P.; Murawski, Allison M.; Pokkali, Supriya; MacDonald, Elizabeth M.; Klunk, Mariah; Mease, Ronnie C.; Pomper, Martin G.; Jain, Sanjay K.

2015-01-01

The Enterobacteriaceae are a family of rod-shaped Gram-negative bacteria that normally inhabit the gastrointestinal tract and are the most common cause of Gram-negative bacterial infections in humans. In addition to causing serious multidrug-resistant, hospital-acquired infections, a number of Enterobacteriaceae species are also recognized as biothreat pathogens. As a consequence, new tools are urgently needed to specifically identify and localize infections due to Enterobacteriaceae and to monitor antimicrobial efficacy. In this report, we used commercially available 2-[18F]-fluorodeoxyglucose (18F-FDG) to produce 2-[18F]-fluorodeoxysorbitol (18F-FDS), a radioactive probe for Enterobacteriaceae, in 30 min. 18F-FDS selectively accumulated in Enterobacteriaceae, but not in Gram-positive bacteria or healthy mammalian or cancer cells in vitro. In a murine myositis model, 18F-FDS positron emission tomography (PET) rapidly differentiated true infection from sterile inflammation with a limit of detection of 6.2 ± 0.2 log10 colony-forming units (CFU) for Escherichia coli. Our findings were extended to models of mixed Gram-positive and Gram-negative thigh co-infections, brain infection, Klebsiella pneumonia, and mice undergoing immunosuppressive chemotherapy. This technique rapidly and specifically localized infections due to Enterobacteriaceae, providing a three-dimensional holistic view within the animal. Last, 18F-FDS PET monitored the efficacy of antimicrobial treatment, demonstrating a PET signal proportionate to the bacterial burden. Therapeutic failures associated with multidrug-resistant, extended-spectrum β-lactamase (ESBL)–producing E. coli infections were detected in real time. Together, these data show that 18F-FDS is a candidate imaging probe for translation to human clinical cases of known or suspected infections owing to Enterobacteriaceae. PMID:25338757

Spatiotemporal modelling of viral infection dynamics

NASA Astrophysics Data System (ADS)

Beauchemin, Catherine

Viral kinetics have been studied extensively in the past through the use of ordinary differential equations describing the time evolution of the diseased state in a spatially well-mixed medium. However, emerging spatial structures such as localized populations of dead cells might affect the spread of infection, similar to the manner in which a counter-fire can stop a forest fire from spreading. In the first phase of the project, a simple two-dimensional cellular automaton model of viral infections was developed. It was validated against clinical immunological data for uncomplicated influenza A infections and shown to be accurate enough to adequately model them. In the second phase of the project, the simple two-dimensional cellular automaton model was used to investigate the effects of relaxing the well-mixed assumption on viral infection dynamics. It was shown that grouping the initially infected cells into patches rather than distributing them uniformly on the grid reduced the infection rate as only cells on the perimeter of the patch have healthy neighbours to infect. Use of a local epithelial cell regeneration rule where dead cells are replaced by healthy cells when an immediate neighbour divides was found to result in more extensive damage of the epithelium and yielded a better fit to experimental influenza A infection data than a global regeneration rule based on division rate of healthy cell. Finally, the addition of immune cell at the site of infection was found to be a better strategy at low infection levels, while addition at random locations on the grid was the better strategy at high infection level. In the last project, the movement of T cells within lymph nodes in the absence of antigen, was investigated. Based on individual T cell track data captured by two-photon microscopy experiments in vivo, a simple model was proposed for the motion of T cells. This is the first step towards the implementation of a more realistic spatiotemporal model of HIV than

Discrete virus infection model of hepatitis B virus.

PubMed

Zhang, Pengfei; Min, Lequan; Pian, Jianwei

2015-01-01

In 1996 Nowak and his colleagues proposed a differential equation virus infection model, which has been widely applied in the study for the dynamics of hepatitis B virus (HBV) infection. Biological dynamics may be described more practically by discrete events rather than continuous ones. Using discrete systems to describe biological dynamics should be reasonable. Based on one revised Nowak et al's virus infection model, this study introduces a discrete virus infection model (DVIM). Two equilibriums of this model, E1 and E2, represents infection free and infection persistent, respectively. Similar to the case of the basic virus infection model, this study deduces a basic virus reproductive number R0 independing on the number of total cells of an infected target organ. A proposed theorem proves that if the basic virus reproductive number R0<1 then the virus free equilibrium E1 is locally stable. The DVIM is more reasonable than an abstract discrete susceptible-infected-recovered model (SIRS) whose basic virus reproductive number R0 is relevant to the number of total cells of the infected target organ. As an application, this study models the clinic HBV DNA data of a patient who was accepted via anti-HBV infection therapy with drug lamivudine. The results show that the numerical simulation is good in agreement with the clinic data.

Biofilm models of polymicrobial infection.

PubMed

Gabrilska, Rebecca A; Rumbaugh, Kendra P

2015-01-01

Interactions between microbes are complex and play an important role in the pathogenesis of infections. These interactions can range from fierce competition for nutrients and niches to highly evolved cooperative mechanisms between different species that support their mutual growth. An increasing appreciation for these interactions, and desire to uncover the mechanisms that govern them, has resulted in a shift from monomicrobial to polymicrobial biofilm studies in different disease models. Here we provide an overview of biofilm models used to study select polymicrobial infections and highlight the impact that the interactions between microbes within these biofilms have on disease progression. Notable recent advances in the development of polymicrobial biofilm-associated infection models and challenges facing the study of polymicrobial biofilms are addressed.

Biofilm models of polymicrobial infection

PubMed Central

Gabrilska, Rebecca A; Rumbaugh, Kendra P

2015-01-01

Interactions between microbes are complex and play an important role in the pathogenesis of infections. These interactions can range from fierce competition for nutrients and niches to highly evolved cooperative mechanisms between different species that support their mutual growth. An increasing appreciation for these interactions, and desire to uncover the mechanisms that govern them, has resulted in a shift from monomicrobial to polymicrobial biofilm studies in different disease models. Here we provide an overview of biofilm models used to study select polymicrobial infections and highlight the impact that the interactions between microbes within these biofilms have on disease progression. Notable recent advances in the development of polymicrobial biofilm-associated infection models and challenges facing the study of polymicrobial biofilms are addressed. PMID:26592098

Managing Knee Osteoarthritis: The Effects of Body Weight Supported Physical Activity on Joint Pain, Function, and Thigh Muscle Strength.

PubMed

Peeler, Jason; Christian, Mathew; Cooper, Juliette; Leiter, Jeffrey; MacDonald, Peter

2015-11-01

To determine the effect of a 12-week lower body positive pressure (LBPP)-supported low-load treadmill walking program on knee joint pain, function, and thigh muscle strength in overweight patients with knee osteoarthritis (OA). Prospective, observational, repeated measures investigation. Community-based, multidisciplinary sports medicine clinic. Thirty-one patients aged between 55 and 75 years, with a body mass index ≥25 kg/m and mild-to-moderate knee OA. Twelve-week LBPP-supported low-load treadmill walking regimen. Acute knee joint pain (visual analog scale) during full weight bearing treadmill walking, chronic knee pain, and joint function [Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire] during normal activities of daily living, and thigh muscle strength (isokinetic testing). Appropriate methods of statistical analysis were used to compare data from baseline and follow-up evaluation. Participants reported significant improvements in knee joint pain and function and demonstrated significant increases in thigh muscle strength about the degenerative knee. Participants also experienced significant reductions in acute knee pain during full weight bearing treadmill walking and required dramatically less LBPP support to walk pain free on the treadmill. Data suggest that an LBPP-supported low-load exercise regimen can be used to significantly diminish knee pain, enhance joint function, and increase thigh muscle strength, while safely promoting pain-free walking exercise in overweight patients with knee OA. These findings have important implications for the development of nonoperative treatment strategies that can be used in the management of joint symptoms associated with progressive knee OA in at-risk patient populations. This research suggests that LBPP-supported low-load walking is a safe user-friendly mode of exercise that can be successfully used in the management of day-to-day joint symptoms associated with knee OA, helping to improve the

Animal models of external traumatic wound infections

PubMed Central

Dai, Tianhong; Kharkwal, Gitika B; Tanaka, Masamitsu; Huang, Ying-Ying; Bil de Arce, Vida J

2011-01-01

Background: Despite advances in traumatic wound care and management, infections remain a leading cause of mortality, morbidity and economic disruption in millions of wound patients around the world. Animal models have become standard tools for studying a wide array of external traumatic wound infections and testing new antimicrobial strategies. Results: Animal models of external traumatic wound infections reported by different investigators vary in animal species used, microorganism strains, the number of microorganisms applied, the size of the wounds and for burn infections, the length of time the heated object or liquid is in contact with the skin. Methods: This review covers experimental infections in animal models of surgical wounds, skin abrasions, burns, lacerations, excisional wounds and open fractures. Conclusions: As antibiotic resistance continues to increase, more new antimicrobial approaches are urgently needed. These should be tested using standard protocols for infections in external traumatic wounds in animal models. PMID:21701256

Muscle-skeletal model of the thigh: a tool for understanding the biomechanics of gait in patients with cerebral palsy

NASA Astrophysics Data System (ADS)

Ravera, Emiliano Pablo; Catalfamo Formento, Paola Andrea; José Crespo, Marcos; Andrés Braidot, Ariel

2011-12-01

Cerebral Palsy represents the most common cause of physical disability in modern world and within the pediatrics orthopedics units. The gait analysis provides great contributions to the understanding of gait disorders in CP. Giving a more comprehensive treatment plan, including or excluding surgical procedures that can potentially decrease the number of surgical interventions in the life of these patients. Recommendations for orthopedic surgery may be based on a quantitative description of how to alter the properties probably muscle force generation, and how this affects the action of the muscle to determine how these muscles, impaired by disease or surgery, contributing to the movement of the segments of the limb during crouch gait. So the causes and appropriate treatment of gait abnormalities are difficult to determine because the movements generated by the muscular forces of these patients are not clearly understood. A correct determination of the etiology of abnormal patterns of the knee is the key to select the appropriate therapy, presenting a major challenge at present since there is no theoretical basis to determine the biomechanical causes of abnormal gait of these patients. The potential and necessity of using correct biomechanical models that consistently study the abnormalities becomes clear. Reinforcing and correcting a simple gait analysis and eliminating the unknowns when selecting the appropriate treatment is crucial in clinical settings. In this paper a computer muscle-skeletal model is proposed. The model represents a person's thigh simulating the six most representative muscles and joints of the hip and knee. In this way you can have a better understanding of gait abnormalities present in these patients. So the quality of these estimates of individual muscle dynamics facilitate better understanding of the biomechanics of gait pathologies helping to reach better diagnosis prior to surgery and rehabilitation treatments.

Systems Biology and Bioinformatics in Medical Applications

DTIC Science & Technology

2009-10-01

animal models, including murine (21, 22, 25, 26, 31, 36) and guinea pig (4) pneumonia models, a rat thigh infection model (27), and a rabbit endocarditis ...Acinetobacter baumannii endocarditis . Clin. Mi- crobiol. Infect. 10:581–584. 36. Rodriguez-Hernandez, M. J., J. Pachon, C. Pichardo, L. Cuberos, J. Ibanez

Double-Pedicled Free Deep Inferior Epigastric Perforator Flap for the Coverage of Thigh Soft-Tissue Defect.

PubMed

Bota, Olimpiu; Spindler, Nick; Sauber, Jeannine; Aydogan, Emrah; Langer, Stefan

2017-08-01

Soft-tissue defects caused by radiation injury are a challenging task for the reconstructive surgeon, due to the extent of the soft-tissue damage and the associated injuries of the local blood vessels and bone tissue. We present the application of the versatile deep inferior epigastric perforator (DIEP) flap for the coverage of an extended lateral thigh soft-tissue defect after the surgical resection of an undifferentiated pleomorphic high-grade sarcoma, neoadjuvant chemotherapy, and adjuvant chemo- and radiotherapy. A double-pedicled free DIEP flap (756 cm 2 ) was harvested and anastomosed to the transverse branch of the lateral femoral circumflex artery and a lateral branch of the popliteal artery (P1). The flap survived completely without serious complications, and the patient was able to walk with crutches 3 months postoperatively. This is the first case report of a free bipedicled DIEP flap for the coverage of a thigh defect in a male patient.

Double-Pedicled Free Deep Inferior Epigastric Perforator Flap for the Coverage of Thigh Soft-Tissue Defect

PubMed Central

Spindler, Nick; Sauber, Jeannine; Aydogan, Emrah; Langer, Stefan

2017-01-01

Summary: Soft-tissue defects caused by radiation injury are a challenging task for the reconstructive surgeon, due to the extent of the soft-tissue damage and the associated injuries of the local blood vessels and bone tissue. We present the application of the versatile deep inferior epigastric perforator (DIEP) flap for the coverage of an extended lateral thigh soft-tissue defect after the surgical resection of an undifferentiated pleomorphic high-grade sarcoma, neoadjuvant chemotherapy, and adjuvant chemo- and radiotherapy. A double-pedicled free DIEP flap (756 cm2) was harvested and anastomosed to the transverse branch of the lateral femoral circumflex artery and a lateral branch of the popliteal artery (P1). The flap survived completely without serious complications, and the patient was able to walk with crutches 3 months postoperatively. This is the first case report of a free bipedicled DIEP flap for the coverage of a thigh defect in a male patient. PMID:28894652

Does thighplasty for upper thigh laxity after massive weight loss require a vertical incision?

PubMed

Shermak, Michele A; Mallalieu, Jessie; Chang, David

2009-01-01

After massive weight loss (MWL), many patients present with concerns about skin excess and laxity. The thigh is one of the more complex regions to address in MWL patients because of the differing degree, location, and quality of skin excess and fatty tissue, as well as surgical risk factors. The authors describe a technique called the anterior proximal extended (APEX) thighlift to effectively treat upper thigh skin excess with a hidden scar while also enhancing adjacent body regions. A review was performed of 97 MWL patients who underwent thighlift surgery between March 1998 and October 2007. Eighty-six women and 11 men, with average weight loss of 146 lb and average body mass index (BMI) at contouring of 29.8, were included in the study. The risk factors that were assessed included age, gender, medical conditions, tobacco use, BMI, weight of skin excised, and surgery performed. The outcomes that were assessed included wound healing and lymphedema. Extended vertical thighlift was performed in 11 patients and anterior superior thighlift in 86 patients. Complications of thighlift included wound healing problems (n = 18; 18.6%); lymphedema (n = 8; 8.3%); cellulitis (n = 7; 7.2%); seroma (n = 3; 3.1%); and bleeding (n = 1; 1%). On multivariate statistical analysis, age and BMI were found to impair healing in the entire thighlift group. For patients with a BMI greater than or equal to 35, the odds ratio (OR) for a wound healing complication was 13.7 (P = .03). Hypothyroidism was strongly associated with lymphedema, with an OR of 23 (P = .06). Extended thighlift trended toward lymphedema (OR = 16.7; P = .08). Thighlift can be a satisfying procedure for both the patient and surgeon because it provides aesthetic improvement in terms of skin excess and laxity. The APEX thighlift is a new technique that expands upon those previously described in the literature to effectively treat upper thigh laxity with a hidden scar after MWL.

Feasibility and Advantages of Full Thickness Skin Graft from the Anterolateral Thigh.

PubMed

Shin, Seung-Han; Kim, Chulkyu; Lee, Yong-Suk; Kang, Jin-Woo; Chung, Yang-Guk

2017-12-01

Full thickness skin graft (FTSG) gives better outcomes than split thickness skin graft (STSG), but it has the drawback of limited donor sites. Anterolateral thigh (ALT), a popular donor site of STSG, is also a popular donor site of perforator flaps. This area has the advantage of large flap size available with primary closure. Based on this we harvested FTSG instead of STSG from the ALT. We retrospectively reviewed 10 cases of FTSG from the ALT, with the recipient site of foot in 3, ankle in 2, lower leg in 2, forearm in 2, and wrist in 1 patient. In all cases elliptical full thickness skin was harvested from the ALT, and the donor site was closed primarily. The skin was defatted and placed onto the defect with vacuum-assisted closure (VAC). The skin size ranged 7-30 cm in length and 3-12 cm in width. Mean follow up period was 7 months (range, 3-13). FTSG from the ALT provided durable wound coverage, with excellent color and texture matching. Partial (< 20%) graft failure was observed in 1 case, but no additional surgery was necessary. No patient reported donor site pain at postoperative 2 weeks. No donor site complications were encountered. No patient complained a feeling of tension in the thigh at final follow-up. FTSG from the ALT is feasible with the aid of VAC. Considering the skin quality, large skin size available, early pain relief, and little donor site morbidity, the ALT should be revisited as a donor site of FTSG.

Assessment of Intraocular and Systemic Vasculature Pressure Parameters in Simulated Microgravity with Thigh Cuff Countermeasure

NASA Technical Reports Server (NTRS)

Huang, Alex S.; Balasubramanian, Siva; Tepelus, Tudor; Sadda, Jaya; Sadda, Srinivas; Stenger, Michael B.; Lee, Stuart M. C.; Laurie, Steve S.; Liu, John; Macias, Brandon R.

2017-01-01

Changes in vision have been well documented among astronauts during and after long-duration space flight. One hypothesis is that the space flight induced headward fluid alters posterior ocular pressure and volume and may contribute to visual acuity decrements. Therefore, we evaluated venoconstrictive thigh cuffs as a potential countermeasure to the headward fluid shift-induced effects on intraocular pressure (IOP) and cephalic vascular pressure and volumes.

The 6-minute walk test, motor function measure and quantitative thigh muscle MRI in Becker muscular dystrophy: A cross-sectional study.

PubMed

Fischer, Dirk; Hafner, Patricia; Rubino, Daniela; Schmid, Maurice; Neuhaus, Cornelia; Jung, Hans; Bieri, Oliver; Haas, Tanja; Gloor, Monika; Fischmann, Arne; Bonati, Ulrike

2016-07-01

Becker muscular dystrophy (BMD) has an incidence of 1 in 16 000 male births. This cross-sectional study investigated the relation between validated functional scores and quantitative MRI (qMRI) of thigh muscles in 20 ambulatory BMD patients, aged 18.3-60 years (mean 31.2; SD 11.1). Clinical assessments included the motor function measure (MFM) and its subscales, as well as timed function tests such as the 6-minute walk test (6MWT) and the timed 10-m run/walk test. Quantitative MRI of the thigh muscles included the mean fat fraction (MFF) using a 2-point Dixon (2-PD) technique, and transverse relaxation time (T2) measurements. The mean MFM value was 80.4%, SD 9.44 and the D1 subscore 54.5%, SD 19.9. The median 6MWT was 195m, IQR 160-330.2. The median 10-m run/walk test was 7.4 seconds, IQR 6.1-9.3. The mean fat fraction of the thigh muscles was 55.6%, SD 17.4%, mean T2 relaxation times of all muscles: 69.9 ms, SD 14.4. The flexors had the highest MFF and T2 relaxation times, followed by the extensors and the adductors. MFF and global T2 relaxation times were highly negatively correlated with the MFM total, D1-subscore and 6MWT, and positively correlated with the 10 m run/walk test time (p < 0.01). Age was not correlated with MFF, global T2 relaxation time or clinical assessments. Both MFF and T2 measures in the thigh muscle were well correlated with clinical function in BMD and may serve as a surrogate outcome measure in clinical trials. Copyright © 2016 Elsevier B.V. All rights reserved.

Improvement of the Pharmacokinetics and In Vivo Antibacterial Efficacy of a Novel Type IIa Topoisomerase Inhibitor by Formulation in Liposomes

PubMed Central

Newman, Joseph; Goteti, Kosalaram; Beaudoin, Marie-Eve; Harrison, Rane; Hopkins, Sussie; Agrawal, Nikunj; Rivin, Olga

2013-01-01

Several useful properties of liposome-based formulations of various existing antibacterial drugs have been reported. These properties include lower MICs, improved pharmacokinetics, lower toxicity, selective distribution to infected tissues, and enhanced in vivo efficacy. Here we report in vivo studies of a liposomal formulation of a member of a novel class of antibacterial type II topoisomerase inhibitors, others of which have progressed to early phases of clinical trials. The free (i.e., nonliposomal) compound has broad-spectrum MICs but suboptimal pharmacokinetics in rats and mice, characterized by a high volume of distribution and rapid clearance. The liposomal formulation of the compound had essentially unchanged MICs but greatly reduced volume of distribution and clearance in rats and mice. In an in vivo mouse model of Staphylococcus aureus infection of one thigh, the liposomal compound localized preferentially to the infected thigh, whereas the free compound showed no preference for the infected versus the uninfected thigh. Most importantly, the liposomal compound had enhanced efficacy at clearing the infection compared with the free compound. Delivery of this class of compounds as liposomal formulations may offer clinical advantages compared with free compounds. PMID:23877679

Synthesis, 68Ga-Radiolabeling, and Preliminary In Vivo Assessment of a Depsipeptide-Derived Compound as a Potential PET/CT Infection Imaging Agent

PubMed Central

Mokaleng, Botshelo B.; Ebenhan, Thomas; Ramesh, Suhas; Govender, Thavendran; Kruger, Hendrik G.; Hazari, Puja P.; Mishra, Anil K.; Marjanovic-Painter, Biljana; Zeevaart, Jan R.; Sathekge, Mike M.

2015-01-01

Noninvasive imaging is a powerful tool for early diagnosis and monitoring of various disease processes, such as infections. An alarming shortage of infection-selective radiopharmaceuticals exists for overcoming the diagnostic limitations with unspecific tracers such as 67/68Ga-citrate or 18F-FDG. We report here TBIA101, an antimicrobial peptide derivative that was conjugated to DOTA and radiolabeled with 68Ga for a subsequent in vitro assessment and in vivo infection imaging using Escherichia coli-bearing mice by targeting bacterial lipopolysaccharides with PET/CT. Following DOTA-conjugation, the compound was verified for its cytotoxic and bacterial binding behaviour and compound stability, followed by 68Gallium-radiolabeling. µPET/CT using 68Ga-DOTA-TBIA101 was employed to detect muscular E. coli-infection in BALB/c mice, as warranted by the in vitro results. 68Ga-DOTA-TBIA101-PET detected E. coli-infected muscle tissue (SUV = 1.3–2.4) > noninfected thighs (P = 0.322) > forearm muscles (P = 0.092) > background (P = 0.021) in the same animal. Normalization of the infected thigh muscle to reference tissue showed a ratio of 3.0 ± 0.8 and a ratio of 2.3 ± 0.6 compared to the identical healthy tissue. The majority of the activity was cleared by renal excretion. The latter findings warrant further preclinical imaging studies of greater depth, as the DOTA-conjugation did not compromise the TBIA101's capacity as targeting vector. PMID:25699267

Diffusion-Tensor Imaging of Thigh Muscles in Duchenne Muscular Dystrophy: Correlation of Apparent Diffusion Coefficient and Fractional Anisotropy Values With Fatty Infiltration.

PubMed

Li, Gui Dian; Liang, Ying Yin; Xu, Ping; Ling, Jian; Chen, Ying Ming

2016-04-01

The purpose of this study is to investigate the correlation of apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values with fatty infiltration in the thigh muscles of patients with Duchenne muscular dystrophy (DMD) using diffusion-tensor imaging (DTI). Twenty-one boys with DMD were recruited. The grade of fatty infiltration and the ADC and FA values of four thigh muscles (rectus femoris, semitendinosus, sartorius, and gracilis) were measured, and the FA and ADC values were compared with the grade of fatty infiltration. Twenty age-matched healthy boys were enrolled as the control group. The differences in the ADC and FA values of the thigh muscles between patients with DMD and the control group were compared. The patients with DMD showed lower FA values and higher ADC values in all measured muscles when compared with the control group. The FA and ADC values were correlated with the grade of fatty infiltration. For the rectus femoris muscle, r = -0.753 and p = 0.007 for FA, and r = 0.685 and p = 0.001 for ADC. For the semitendinosus muscle, r = -0.621 and p = 0.041 for FA, and r = 0.705 and p = 0.021 for ADC. For the sartorius muscle, r = -0.662 and p = 0.027 for FA, and r = 0.701 and p = 0.017 for ADC. For the gracilis muscle, r = -0.618 and p = 0.043 for FA, and r = 0.695 and p = 0.022 for ADC. Damage to the thigh muscles in patients with DMD can be detected by ADC and FA values using DTI. DTI can be used to assess the severity of the disease.

Brood amalgamation in the Bristle-thighed Curlew Numenius tahitiensis: process and function

USGS Publications Warehouse

Lanctot, Richard B.; Gill, Robert E.; Tibbitts, T.L.; Handel, Colleen M.

1995-01-01

Alloparental care in birds generally involves nonbreeding adults that help at nests or breeding adults that help raise young in communal nests. A less often reported form involves the amalgamation of broods, where one or more adults care for young that are not their own. We observed this phenomenon among Bristle-thighed Curlew Numenius tahitiensis broods in western Alaska during 1990–1992. Amalgamation of broods generally involved the formation of temporary and extended associations. Temporary associations were formed by the incidental convergence of broods soon after they left their nests. During this period, parents defended distinct brood-rearing areas, were antagonistic to conspecifics and remained together for less than 3 days. Extended associations formed when chicks were 1–2 weeks old. Here, parents and their broods occupied distinct, but adjacent, brood-rearing areas and moved around as a unit. Whether a brood participated in either temporary or extended associations or remained solitary appeared to depend on brood density in the immediate area and on hatching date. When chicks were 3–4 weeks old, aggregations of up to ten broods formed wherein young mixed and parents defended a common brood-rearing area. All broods (n = 48) that survived to fledging joined such aggregations. Alloparental care involved only antipredator defence and was not associated with activities such as feeding and brooding. Most female parents abandoned their broods shortly after the young could fly and when aggregations were forming. The female parent of a pair always deserted its young before or on the same day as the male parent and, in every aggregation, one or two males continued to tend young for about 5 days longer than other male parents. In most cases, adults deserted the young 2–6 days before the young departed the area when about 38 days old. Bristle-thighed Curlews also formed temporary associations with American and Pacific Golden Plover Pluvialis dominica and

Orthopedic pathology of the lower extremities: scintigraphic evaluation in the thigh, knee, and leg.

PubMed

Etchebehere, E C; Etchebehere, M; Gamba, R; Belangero, W; Camargo, E E

1998-01-01

Radionuclide imaging (RI) of the osseous and nonosseous structures of the thigh, knee, and leg provide important diagnostic and prognostic information upon which the orthopedic surgeon can base treatment planning and management decisions. 99mTc-MDP scintigraphy is essential in overuse injuries such as stress fractures and shin splints. RI is important in assessing complications of trauma. It is the only imaging modality able to assess the magnitude of physeal stimulus caused by femoral fractures and to predict a favorable or unfavorable outcome of leg length by semiquantitative analysis; SPECT imaging can detect and locate decreased metabolism associated with posttraumatic closure of the physeal plate to predict growth arrest and deformities. Three-phase bone imaging (TPBI) is essential to differentiate hypervascular from avascular nonunions and follow delayed union. In osteonecrosis of the knee, bone scintigraphy precedes radiography changes even in stage l of the disease. 99mTc-MDP and 99mTc-HIG imaging are powerful tools in determining the outcomes of osteoarthritis and rheumatoid arthritis, respectively. Bone scintigraphy can also detect chronic ligament and acute and chronic meniscal lesions. The combined use of TPBI, gallium-67 citrate imaging, and indium-111 or 99mTc-HMPAO labeled leukocytes is important to diagnose and differentiate acute from chronic osteomyelitis, and to detect infected knee prostheses. Thallium-201 chloride imaging and 99mTc-sestamibi imaging have an important role in the assessment of tumor response to chemotherapy and in the quantification of tumor viability.

Progression and variation of fatty infiltration of the thigh muscles in Duchenne muscular dystrophy, a muscle magnetic resonance imaging study.

PubMed

Li, Wenzhu; Zheng, Yiming; Zhang, Wei; Wang, Zhaoxia; Xiao, Jiangxi; Yuan, Yun

2015-05-01

The purpose of this study was to assess the progression and variation of fatty infiltration of the thigh muscles of Duchenne muscular dystrophy patients. Muscle magnetic resonance imaging was used to measure the degree of fatty infiltration of the thigh muscles of 171 boys with Duchenne muscular dystrophy (mean age, 6.09 ± 2.30 years). Fatty infiltration was assigned using a modified Mercuri's scale 0-5 (normal-severe). The gluteus maximus and adductor magnus were affected in patients less than two years old, followed by the biceps femoris. Quadriceps and semimembranosus were first affected at the age of five to six years; the sartorius, gracilis and adductor longus remained apparently unaffected until seven years of age. Fatty infiltration of all the thigh muscles developed rapidly after seven years of age. The standard deviation of the fatty infiltration scores ranged from 2.41 to 4.87 before five years old, and from 6.84 to 11.66 between six and ten years old. This study provides evidence of highly variable degrees of fatty infiltration in children of different ages with Duchenne muscular dystrophy, and indicates that fatty infiltration progresses more quickly after seven years of age. These findings may be beneficial for the selection of therapeutic regimens and the analysis of future clinical trials. Copyright © 2015 Elsevier B.V. All rights reserved.

Differentiation of fat, muscle, and edema in thigh MRIs using random forest classification

NASA Astrophysics Data System (ADS)

Kovacs, William; Liu, Chia-Ying; Summers, Ronald M.; Yao, Jianhua

2016-03-01

There are many diseases that affect the distribution of muscles, including Duchenne and fascioscapulohumeral dystrophy among other myopathies. In these disease cases, it is important to quantify both the muscle and fat volumes to track the disease progression. There has also been evidence that abnormal signal intensity on the MR images, which often is an indication of edema or inflammation can be a good predictor for muscle deterioration. We present a fully-automated method that examines magnetic resonance (MR) images of the thigh and identifies the fat, muscle, and edema using a random forest classifier. First the thigh regions are automatically segmented using the T1 sequence. Then, inhomogeneity artifacts were corrected using the N3 technique. The T1 and STIR (short tau inverse recovery) images are then aligned using landmark based registration with the bone marrow. The normalized T1 and STIR intensity values are used to train the random forest. Once trained, the random forest can accurately classify the aforementioned classes. This method was evaluated on MR images of 9 patients. The precision values are 0.91+/-0.06, 0.98+/-0.01 and 0.50+/-0.29 for muscle, fat, and edema, respectively. The recall values are 0.95+/-0.02, 0.96+/-0.03 and 0.43+/-0.09 for muscle, fat, and edema, respectively. This demonstrates the feasibility of utilizing information from multiple MR sequences for the accurate quantification of fat, muscle and edema.

Clinical utility of colour flow Doppler ultrasonography in planning anterolateral thigh flap harvest.

PubMed

Patel, Rajan S; Higgins, Kevin M; Enepekides, Danny J; Hamilton, Paul A

2010-10-01

The anatomic variability of cutaneous perforators contributes to the technical challenges of anterolateral thigh (ALT) free flap harvest. The objective of this study was to assess the accuracy and clinical utility of preoperative colour flow Doppler (CFD) ultrasonography in evaluating planned ALT flap donor sites. A prospective study of the infrainguinal vasculature (profunda femoris and lateral circumflex femoral arteries) in 16 consecutive patients scheduled for ALT free flap transfer for reconstruction of head and neck surgical defects was undertaken. All patients underwent CFD ultrasonography. The location of perforators and the thigh thickness determined by CFD ultrasonography were correlated with the actual intraoperative findings using a scatter plot and paired t-test. Two patients were diagnosed with bilateral silent infrainguinal claudication, which precluded safe use of the ALT donor site. In two other patients, the planned ALT donor site ipsilateral to the defect was not used because of silent infrainguinal claudication diagnosed by CFD ultrasonography. In the 14 patients who underwent ALT flap harvest, CFD ultrasonography identified 48 perforators, which coincided with 43 actual perforators found intraoperatively. CFD ultrasonography demonstrated a statistically significant correlation with the actual perforator locations (Spearman coefficient .76; p = .55). Although CFD ultrasonography tended to underestimate flap thickness, there was a statistically significant correlation (Spearman coefficient .94; p ≤ .0001) with the actual flap thickness. CFD ultrasonography has clinical utility in facilitating decision making and planning ALT flap harvest.

Animal model for hepatitis C virus infection.

PubMed

Tsukiyama-Kohara, Kyoko; Kohara, Michinori

2015-01-01

Hepatitis C virus (HCV) infects more than 170 million people in the world and chronic HCV infection develops into cirrhosis and hepatocellular carcinoma (HCC). Recently, the effective compounds have been approved for HCV treatment, the protease inhibitor and polymerase inhibitor (direct acting antivirals; DAA). DAA-based therapy enabled to cure from HCV infection. However, development of new drug and vaccine is still required because of the generation of HCV escape mutants from DAA, development of HCC after treatment of DAA, and the high cost of DAA. In order to develop new anti-HCV drug and vaccine, animal infection model of HCV is essential. In this manuscript, we would like to introduce the history and the current status of the development of HCV animal infection model.

Effects of distribution of infection rate on epidemic models

NASA Astrophysics Data System (ADS)

Lachiany, Menachem; Louzoun, Yoram

2016-08-01

A goal of many epidemic models is to compute the outcome of the epidemics from the observed infected early dynamics. However, often, the total number of infected individuals at the end of the epidemics is much lower than predicted from the early dynamics. This discrepancy is argued to result from human intervention or nonlinear dynamics not incorporated in standard models. We show that when variability in infection rates is included in standard susciptible-infected-susceptible (SIS ) and susceptible-infected-recovered (SIR ) models the total number of infected individuals in the late dynamics can be orders lower than predicted from the early dynamics. This discrepancy holds for SIS and SIR models, where the assumption that all individuals have the same sensitivity is eliminated. In contrast with network models, fixed partnerships are not assumed. We derive a moment closure scheme capturing the distribution of sensitivities. We find that the shape of the sensitivity distribution does not affect R0 or the number of infected individuals in the early phases of the epidemics. However, a wide distribution of sensitivities reduces the total number of removed individuals in the SIR model and the steady-state infected fraction in the SIS model. The difference between the early and late dynamics implies that in order to extrapolate the expected effect of the epidemics from the initial phase of the epidemics, the rate of change in the average infectivity should be computed. These results are supported by a comparison of the theoretical model to the Ebola epidemics and by numerical simulation.

Muscle atrophy and recovery of individual thigh muscles as measured by magnetic resonance imaging scan during treatment with cast for ankle or foot fracture.

PubMed

Yamauchi, Koun; Yoshiko, Akito; Suzuki, Shigetoshi; Kato, Chisato; Akima, Hiroshi; Kato, Takayuki; Ishida, Koji

2017-01-01

We aimed to longitudinally investigate individual thigh muscle changes using magnetic resonance imaging (MRI) during treatment with cast of ankle or foot fracture. Moreover, we aimed to demonstrate whether measurements of muscle cross-sectional area (CSA) are sensitive to muscle changes, contributing to simpler methods in clinical application . Ten patients undergoing treatment with cast of acute ankle or foot fractures were studied. Axial MRI (1.5 T) was conducted around the affected mid-thigh region after the injury (Pre), after maintaining a nonweight-bearing (NWB) period (approximately 28 days), and after finishing rehabilitation (recovery). Regarding individual thigh muscles, the total CSAs corresponding to 40% of the femoral length (FL) and the CSAs at 5% interval of the FL were longitudinally measured. Standardized response means (SRMs) were accessed for sensitivity in the muscle changes. The total CSAs at NWB were significantly lower than those at Pre in vastus lateralis (10.9% ± 5.4%), vastus intermedius (8.4% ± 6.7%), and vastus medialis (11.2% ± 6.9%) ( p < 0.01 for all). In contrast, at recovery, the only significant muscle atrophy relative to that at Pre was observed in the semitendinosus of the proximal 15% and 10% CSAs ( p < 0.01 and p = 0.01, respectively). In all muscles, SRM using a single-slice CSA at or near the muscle belly was high. Thigh muscle changes differ according to the variations in individual muscles. CSA measurements at or near the muscle belly are simple methods and sensitive indicators of these muscle changes.

Animal models for percutaneous-device-related infections: a review.

PubMed

Shao, Jinlong; Kolwijck, Eva; Jansen, John A; Yang, Fang; Walboomers, X Frank

2017-06-01

This review focuses on the construction of animal models for percutaneous-device-related infections, and specifically the role of inoculation of bacteria in such models. Infections around percutaneous devices, such as catheters, dental implants and limb prostheses, are a recurrent and persistent clinical problem. To promote the research on this clinical problem, the establishment of a reliable and validated animal model would be of keen interest. In this review, literature related to percutaneous devices was evaluated, and particular attention was paid to studies involving the use of bacteria. The design of percutaneous devices, susceptibility of various animal species, bacterial strains, amounts of bacteria, method of inoculation and methods for subsequent evaluation of the infection are discussed in detail. Given that an ideal animal model for study of percutaneous-device-related infection is still not existent, this article presents the basis for the construction of such a standardized animal model for percutaneous-device-related infection studies. The inoculation of bacteria is critical to obtain an animal model for standardized studies for percutaneous-device-related infections. Copyright © 2017. Published by Elsevier B.V.

ACUTE EFFECTS OF DIFFERENT ANTERIOR THIGH SELF-MASSAGE ON HIP RANGE-OF-MOTION IN TRAINED MEN.

PubMed

Monteiro, Estêvão Rios; Vigotsky, Andrew D; Novaes, Jefferson da Silva; Škarabot, Jakob

2018-02-01

Self-massage is a ubiquitous intervention similar to massage, but performed by the recipient him- or herself rather than by a therapist, most often using a tool (e.g., foam roller, roller massager). Self-massage has been found to have a wide range of effects. It is particularly known for increasing flexibility acutely, although not always. The variability of the results in previous studies may potentially be a function of the tool used. Recent findings also suggest that self-massage exerts global effects. Therefore, increased flexibility should be expected in the areas adjacent to the ones treated. To investigate the acute effects of foam rolling and rolling massage of anterior thigh on hip range-of-motion (ROM) - i.e., hip extension and hip flexion - in trained men. Eighteen recreationally active, resistance trained males visited the lab on two occasions over a 4-day period separated by at least a day. Each session included two baseline ROM measures of passive hip flexion and extension taken in a randomized fashion. Recording of baseline measures was followed by the intervention of the day, which was either foam rolling or rolling massage of the anterior thigh as per randomization. Immediately post intervention, passive hip flexion and hip extension ROM were reassessed. In order to assess the time course of improvements in ROM, hip flexion and hip extension ROM were reevaluated at 10, 20, and 30 minutes post-intervention. Hip flexion and hip extension ROM increased immediately following both interventions (foam rolling or roller massager) and remained increased for 30 minutes post intervention. Foam rolling was statistically superior in improving hip flexion and hip extension ROM immediately post intervention. However, immediately post-intervention was the only time point that measurements exceeded the minimum detectable change for both interventions. Both foam rolling and rolling massage appear to be effective interventions for improving hip flexion and extension

[Forensic medical diagnostics of the extent of the thigh skin injury inflicted by motor vehicles of different weight].

PubMed

Sashko, S Iu; Isakov, V D; Droblenkov, A V

2011-01-01

The authors report the results of an experimental study designed to characterize microstructural changes in the thigh skin caused by the impacts simulating the car wheel loads of different intensity. It was shown that histological methods can be used to discriminate between the intensities of traumatic loading on biological tissues.

0.125 mm(3) spatial resolution steady-state MR angiography of the thighs with a blood pool contrast agent using the quadrature body coil only at 1.5 Tesla.

PubMed

Boschewitz, Jack M; Hadizadeh, Dariusch R; Kukuk, Guido M; Meyer, Carsten; Wilhelm, Kai; Koscielny, Arne; Verrel, Frauke; Gieseke, Jürgen; Schild, Hans H; Willinek, Winfried A

2014-10-01

To implement and evaluate high spatial resolution three-dimensional MR contrast-enhanced angiography (3D-CEMRA) of the thighs using a blood pool contrast agent (BPCA) using the quadrature body coil only in patients with peripheral arterial occlusive disease (PAOD) in cases receiver coils cannot be used at 1.5 Tesla (T). Nineteen patients (mean age: 68.7 ± 11.2 years; range, 38-83 years) with known PAOD (Fontaine stages; III: 16, IV: 3) prospectively underwent 3D-CEMRA at 1.5T with a noninterpolated voxel size of 0.49 × 0.49 × 0.48 mm(3) . Digital subtraction angiography (DSA) was available for comparison in all patients. Two readers independently evaluated movement artifacts, overall image quality of 3D-CEMRA, and grade of stenosis as compared to DSA. SNR and CNR levels were quantified. The 3D-CEMRA was successfully completed in all patients. Patient movement artifacts that affected stenosis grading occurred in 3/38 thighs. Overall image quality was rated excellent in 15/38, good in 12/38, and diagnostic in 8/38 thighs. Stenosis grading matched with that in DSA in 35/38 thighs. High SNR and CNR were measured in all vessels. The 0.125 mm(3) spatial resolution 3D-CEMRA of the thighs with a BPCA is feasible using a quadrature body coil exclusively with excellent image quality despite long acquisition times. J. Magn. Reson. Imaging 2014;40:996-1001. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

Biodistribution of free and encapsulated 99mTc-fluconazole in an infection model induced by Candida albicans.

PubMed

de Assis, Danielle Nogueira; Araújo, Raquel Silva; Fuscaldi, Leonardo Lima; Fernandes, Simone Odília Antunes; Mosqueira, Vanessa Carla Furtado; Cardoso, Valbert Nascimento

2018-03-01

Candida spp is an etiologic agent of fungal infections in hospitals and resistance to treatment with antifungals has been extensively reported. Thus, it is very important to develop formulations that increase effectiveness with low toxicity. In this sense, nanocarriers have been investigated, once they modify drug biodistribution profile. Thus, this study aimed to evaluate the biodistribution of free and encapsulated 99m Tc-fluconazole into nanocapsules (NCs) in an experimental immunosuppressed murine model of Candida albicans infection. Fluconazole was radiolabeled with technetium-99 metastable ( 99m Tc) and encapsulated into conventional ( 99m Tc-Fluconazole-PLA-POLOX) and surface-modified ( 99m Tc-Fluconazole-PLA-PEG) NCs by the interfacial deposition of the preformed biodegradable polymer [poly (D,L-lactic acid) (PLA) and PLA-PEG (polyethyleneglycol)] followed by solvent evaporation. The size distribution and zeta potential of the NCs preparations were determined in a Zetasizer by photon correlation spectroscopy and laser Doppler anemometry, respectively. Free and encapsulated 99m Tc-fluconazole were administered intravenously in immunosuppressed mice bearing a local infection induced by Candida Albicans inoculation in the right thigh muscle. At pre-established time intervals, tissues and organs of interest were removed and radioactivity was measured in an automatic gamma radiation counter. The NCs diameter was between 200 and 400 nm with negative zeta potential values. Free 99m Tc-fluconazole was more rapidly eliminated by the renal system compared to the encapsulated drug in NCs, which remained longer in blood circulation. The uptake of conventional NCs by mononuclear phagocyte system organs was higher than the one demonstrated by the surface-modified NCs. Both NCs remained longer in the infectious focus when compared to free 99m Tc-fluconazole, but the results did not show a significant difference between NC formulations. These data indicate that these NCs

Modeling Influenza Virus Infection: A Roadmap for Influenza Research

PubMed Central

Boianelli, Alessandro; Nguyen, Van Kinh; Ebensen, Thomas; Schulze, Kai; Wilk, Esther; Sharma, Niharika; Stegemann-Koniszewski, Sabine; Bruder, Dunja; Toapanta, Franklin R.; Guzmán, Carlos A.; Meyer-Hermann, Michael; Hernandez-Vargas, Esteban A.

2015-01-01

Influenza A virus (IAV) infection represents a global threat causing seasonal outbreaks and pandemics. Additionally, secondary bacterial infections, caused mainly by Streptococcus pneumoniae, are one of the main complications and responsible for the enhanced morbidity and mortality associated with IAV infections. In spite of the significant advances in our knowledge of IAV infections, holistic comprehension of the interplay between IAV and the host immune response (IR) remains largely fragmented. During the last decade, mathematical modeling has been instrumental to explain and quantify IAV dynamics. In this paper, we review not only the state of the art of mathematical models of IAV infection but also the methodologies exploited for parameter estimation. We focus on the adaptive IR control of IAV infection and the possible mechanisms that could promote a secondary bacterial coinfection. To exemplify IAV dynamics and identifiability issues, a mathematical model to explain the interactions between adaptive IR and IAV infection is considered. Furthermore, in this paper we propose a roadmap for future influenza research. The development of a mathematical modeling framework with a secondary bacterial coinfection, immunosenescence, host genetic factors and responsiveness to vaccination will be pivotal to advance IAV infection understanding and treatment optimization. PMID:26473911

Modeling Influenza Virus Infection: A Roadmap for Influenza Research.

PubMed

Boianelli, Alessandro; Nguyen, Van Kinh; Ebensen, Thomas; Schulze, Kai; Wilk, Esther; Sharma, Niharika; Stegemann-Koniszewski, Sabine; Bruder, Dunja; Toapanta, Franklin R; Guzmán, Carlos A; Meyer-Hermann, Michael; Hernandez-Vargas, Esteban A

2015-10-12

Influenza A virus (IAV) infection represents a global threat causing seasonal outbreaks and pandemics. Additionally, secondary bacterial infections, caused mainly by Streptococcus pneumoniae, are one of the main complications and responsible for the enhanced morbidity and mortality associated with IAV infections. In spite of the significant advances in our knowledge of IAV infections, holistic comprehension of the interplay between IAV and the host immune response (IR) remains largely fragmented. During the last decade, mathematical modeling has been instrumental to explain and quantify IAV dynamics. In this paper, we review not only the state of the art of mathematical models of IAV infection but also the methodologies exploited for parameter estimation. We focus on the adaptive IR control of IAV infection and the possible mechanisms that could promote a secondary bacterial coinfection. To exemplify IAV dynamics and identifiability issues, a mathematical model to explain the interactions between adaptive IR and IAV infection is considered. Furthermore, in this paper we propose a roadmap for future influenza research. The development of a mathematical modeling framework with a secondary bacterial coinfection, immunosenescence, host genetic factors and responsiveness to vaccination will be pivotal to advance IAV infection understanding and treatment optimization.

Thermal inactivation of H5N1 high pathogenicity avian influenza virus in naturally infected chicken meat.

PubMed

Thomas, Colleen; Swayne, David E

2007-03-01

Thermal inactivation of the H5N1 high pathogenicity avian influenza (HPAI) virus strain A/chicken/Korea/ES/2003 (Korea/03) was quantitatively measured in thigh and breast meat harvested from infected chickens. The Korea/03 titers were recorded as the mean embryo infectious dose (EID50) and were 10(8.0) EID50/g in uncooked thigh samples and 10(7.5) EID50/g in uncooked breast samples. Survival curves were constructed for Korea/03 in chicken thigh and breast meat at 1 degrees C intervals for temperatures of 57 to 61 degrees C. Although some curves had a slightly biphasic shape, a linear model provided a fair-to-good fit at all temperatures, with R2 values of 0.85 to 0.93. Stepwise linear regression revealed that meat type did not contribute significantly to the regression model and generated a single linear regression equation for z-value calculations and D-value predictions for Korea/03 in both meat types. The z-value and the upper limit of the 95% confidence interval for the z-value were 4.64 and 5.32 degrees C, respectively. From the lowest temperature to the highest, the predicted D-values and the upper limits of their 95% prediction intervals (conservative D-values) for 57 to 61 degrees C were 241.2 and 321.1 s, 146.8 and 195.4 s, 89.3 and 118.9 s, 54.4 and 72.4 s, and 33.1 and 44.0 s. D-values and conservative D-values predicted for higher temperatures were 0.28 and 0.50 s for 70 degrees C and 0.041 and 0.073 s for 73.9 degrees C. Calculations with the conservative D-values predicted that cooking chicken meat according to current U.S. Department of Agriculture Food Safety and Inspection Service time-temperature guidelines will inactivate Korea/03 in a heavily contaminated meat sample, such as those tested in this study, with a large margin of safety.

Experimental Models of C. albicans-Streptococcal Co-infection.

PubMed

Sobue, Takanori; Diaz, Patricia; Xu, Hongbin; Bertolini, Martinna; Dongari-Bagtzoglou, Anna

2016-01-01

Interactions of C. albicans with co-colonizing bacteria at mucosal sites can be synergistic or antagonistic in disease development, depending on the bacterial species and mucosal site. Mitis group streptococci and C. albicans colonize the oral mucosa of the majority of healthy individuals. These streptococci have been termed "accessory pathogens," defined by their ability to initiate multispecies biofilm assembly and promote the virulence of the mixed bacterial biofilm community in which they participate. To demonstrate whether interactions with Mitis group streptococci limit or promote the potential of C. albicans to become an opportunistic pathogen, in vitro and in vivo co-infection models are needed. Here, we describe two C. albicans-streptococcal co-infection models: an organotypic oral mucosal tissue model that incorporates salivary flow and a mouse model of oral co-infection that requires reduced levels of immunosuppression compared to single fungal infection.

Test-retest reliability of myofascial trigger point detection in hip and thigh areas.

PubMed

Rozenfeld, E; Finestone, A S; Moran, U; Damri, E; Kalichman, L

2017-10-01

Myofascial trigger points (MTrP's) are a primary source of pain in patients with musculoskeletal disorders. Nevertheless, they are frequently underdiagnosed. Reliable MTrP palpation is the necessary for their diagnosis and treatment. The few studies that have looked for intra-tester reliability of MTrPs detection in upper body, provide preliminary evidence that MTrP palpation is reliable. Reliability tests for MTrP palpation on the lower limb have not yet been performed. To evaluate inter- and intra-tester reliability of MTrP recognition in hip and thigh muscles. Reliability study. 21 patients (15 males and 6 females, mean age 21.1 years) referred to the physical therapy clinic, 10 with knee or hip pain and 11 with pain in an upper limb, low back, shin or ankle. Two experienced physical therapists performed the examinations, blinded to the subjects' identity, medical condition and results of the previous MTrP evaluation. Each subject was evaluated four times, twice by each examiner in a random order. Dichotomous findings included a palpable taut band, tenderness, referred pain, and relevance of referred pain to patient's complaint. Based on these, diagnosis of latent MTrP's or active MTrP's was established. The evaluation was performed on both legs and included a total of 16 locations in the following muscles: rectus femoris (proximal), vastus medialis (middle and distal), vastus lateralis (middle and distal) and gluteus medius (anterior, posterior and distal). Inter- and intra-tester reliability (Cohen's kappa (κ)) values for single sites ranged from -0.25 to 0.77. Median intra-tester reliability was 0.45 and 0.46 for latent and active MTrP's, and median inter-tester reliability was 0.51 and 0.64 for latent and active MTrPs, respectively. The examination of the distal vastus medialis was most reliable for latent and active MTrP's (intra-tester k = 0.27-0.77, inter-tester k = 0.77 and intra-tester k = 0.53-0.72, inter-tester k = 0.72, correspondingly

[APPLICATION OF DIGITAL TECHNOLOGY IN ANTEROLATERAL THIGH FLAP FOR REPAIRING WOUNDS OF HAND AND FOOT].

PubMed

Duan, Jiazhang; He, Xiaoqing; Xu, Yongqing; Fan, Xinyu; Luo, Haotian; Wang, Teng; Dong, Kaixuan; Yu, Kaifu

2015-07-01

To investigate the effectiveness of digital technology in repairing wounds of the hand and foot with anterolateral thigh flap. Between September 2013 and September 2014, 16 cases of wounds of the hand and foot were treated with the anterolateral thigh flap. There were 10 males and 6 females, with an average age of 31 years (range, 20-52 years). The causes included traffic accident injury in 8 cases, crushing injury by machine in 6 cases, burning injury in 1 case, and animal biting injury in 1 case. The locations of soft tissue defect were the dorsum of the foot in 5 cases, the ankle in 4 cases, the planta pedis in 1 case, and the hand and forearm in 6 cases. The time was 2 hours to 45 days from injury to hospitalization (mean, 14.3 days). All defects were associated with exposure of bone and tendon. The size of wound was from 9.0 cmx4.0 cm to 29.0 cmx8.5 cm. CT angiography (CTA) was performed before operation, and the appropriate perforator as well as the donor site was selected. Then the Mimics l5.0 software was used to reconstruct the data of CTA so as to locate the main perforators, design the three-dimensional models of the anterolateral thigh flap, and simulate operation. The flap was obtained according to preoperative plan during operation. The size of flaps varied from 11 cm x 5 cm to 31 cm x 10 cm. The donor sites were sutured directly in 14 cases and were repaired by free skin graft in 2 cases. The lateral femoral circumflex artery identified by Mimics l5.0 software before operation, as well as the starting position of its descending branch, the blood vessel diameter at start site, vascular distribution, the maximum cutting length of the vascular pedicle were consistent with the actual observation during operation. All flaps were harvested and were used to repair defect smoothly. Vascular crisis occurred in 1 flap after operation, and the other flaps survived successfully. The wounds and the incisions obtained healing by first intention, and grafted skin

Effects of ipsilateral anterior thigh soft tissue stretching on passive unilateral straight-leg raise.

PubMed

Clark, S; Christiansen, A; Hellman, D F; Hugunin, J W; Hurst, K M

1999-01-01

Randomized 3-group pretest-posttest with blind assessment of outcome. The purpose of this study was to examine the effect of sagittal plane hold-relax exercise applied to the ipsilateral anterior thigh, and prone positioning on passive unilateral straight-leg raise measurements. Straight-leg raising has been viewed as a measurement for hamstring muscle length, but literature suggests that other structures may affect this measurement. Sixty subjects (45 men, 15 women) qualified for inclusion into the study based on a straight-leg raise measurement of < or = 65 degrees. Subjects were randomly assigned to one of three groups: control, static stretch, or sagittal plane hold-relax exercise. Pretest and posttest straight-leg raise measurements of the right lower extremity were performed for each subject. A 1-way ANOVA of the change scores showed a significant difference between groups. A Tukey post hoc analysis of the change scores showed that both treatment groups' means differed significantly from the control group and from each other, with the sagittal plane hold-relax group exhibiting the largest change (mean of 7.8 degrees +/- 2.8 degrees). The results of this study show that sagittal plane hold-relax exercise and passive prone results of this study show that sagittal plane hold-relax and passive prone positioning can significantly increase straight-leg raise range of motion, however the sagittal plane hold-relax stretching of the anterior thigh is more effective than passive prone positioning.

Animal models of human immunodeficiency virus infection. Public Health Service Animal Models Committee.

PubMed

Spertzel, R O

1989-12-01

The search for a model of HIV infection continues. While much of the initial work focussed on animal models of AIDS, more recent efforts have sought animal models of HIV infection in which one or more signs of AIDS may be reproduced. Most initial small animal modelling efforts were negative and many such efforts remain unpublished. In 1988, the Public Health Service (PHS) AIDS Animal Model Committee conducted a survey among PHS agencies to identify published and unpublished data on animal models of HIV. To date, the chimpanzee is the only animal to be reliably infected with HIV albeit without development of signs and symptoms normally associated with human AIDS. One recent study has shown the gibbon to be similarly susceptible to infection with HIV. Mice carrying a chimera of elements of the human immune system have been shown to support the growth of HIV and F1 progeny of transgenic mice containing intact copies of HIV proviral DNA, have developed a disease that resembles some aspects of human AIDS. Rabbits, baboons and rhesus monkeys have also been shown to be infected under certain conditions and/or with selected strains of HIV but again without the development of AIDS symptomatology. This report briefly summarizes published and available unpublished data on these efforts to develop an animal model of HIV infection.

Dynamics of delayed pathogen infection models with pathogenic and cellular infections and immune impairment

NASA Astrophysics Data System (ADS)

Elaiw, A. M.; Raezah, A. A.; Alofi, B. S.

2018-02-01

We study the global dynamics of delayed pathogen infection models with immune impairment. Both pathogen-to-susceptible and infected-to-susceptible transmissions have been considered. Bilinear and saturated incidence rates are considered in the first and second model, respectively. We drive the basic reproduction parameter R0 which determines the global dynamics of models. Using Lyapunov method, we established the global stability of the models' steady states. The theoretical results are confirmed by numerical simulations.

Carbon fibre reinforced plastic knee-ankle-foot orthosis with a partially flexible thigh cuff: a modification for comfort while sitting on a toilet seat.

PubMed

Hachisuka, K; Arai, K; Arai, M

2007-06-01

At the request of a polio survivor, a partially flexible thigh cuff made of leather and canvas for a carbon KAFO was devised to allow the wearer to feel more comfortable while sitting on a toilet seat. The original, acrylic resin, thigh cuff was partially excised to make an opening (15x10 cm), which was stuffed with rubber sponge, and was sealed with leather and canvas. The opening's surround was vertically and horizontally reinforced with carbon fibres. This modification provided relief to the polio survivor from the discomfort previously experienced while sitting on a toilet seat, and satisfied her needs in daily life.

Abdominal wall reconstruction using a combination of free tensor fasciae lata and anterolateral thigh myocutaneous flap: a prospective study in 16 patients.

PubMed

Lv, Yang; Cao, Dongsheng; Guo, Fangfang; Qian, Yunliang; Wang, Chen; Wang, Danru

2015-08-01

Reconstruction of the abdominal wall continues to be a challenging problem for plastic surgeons. Transposition of well-vascularized flap tissue is the most effective way to repair composite abdominal wall defects. We retrospectively reviewed the treatment of such patients and assessed the reconstructive technique using combination of an inlay of bioprosthetic materials and a united thigh flap. A retrospective review of patients' records in the department was carried out. In total, 16 patients who underwent immediate abdominal wall reconstruction between 2000 and 2013 were identified. Patients' health status, defect sizes, and surgical technique were obtained from medical charts. The immediate reconstruction surgery of the abdominal wall was successful in all patients. One patient with dermatofibrosarcoma protuberans experienced recurrences at the former site. One patient died because of liver metastases at 21 months after surgery. No incisional hernia or infection in this series of patients was observed. Full-thickness, giant defects of the complicated abdominal wall can be repaired successfully with relatively minor complications using this reconstructive technique. Copyright © 2015 Elsevier Inc. All rights reserved.

Characterization of thigh and shank segment angular velocity during jump landing tasks commonly used to evaluate risk for ACL injury.

PubMed

Dowling, Ariel V; Favre, Julien; Andriacchi, Thomas P

2012-09-01

The dynamic movements associated with anterior cruciate ligament (ACL) injury during jump landing suggest that limb segment angular velocity can provide important information for understanding the conditions that lead to an injury. Angular velocity measures could provide a quick and simple method of assessing injury risk without the constraints of a laboratory. The objective of this study was to assess the inter-subject variations and the sensitivity of the thigh and shank segment angular velocity in order to determine if these measures could be used to characterize jump landing mechanisms. Additionally, this study tested the correlation between angular velocity and the knee abduction moment. Thirty-six healthy participants (18 male) performed drop jumps with bilateral and unilateral landing. Thigh and shank angular velocities were measured by a wearable inertial-based system, and external knee moments were measured using a marker-based system. Discrete parameters were extracted from the data and compared between systems. For both jumping tasks, the angular velocity curves were well defined movement patterns with high inter-subject similarity in the sagittal plane and moderate to good similarity in the coronal and transverse planes. The angular velocity parameters were also able to detect differences between the two jumping tasks that were consistent across subjects. Furthermore, the coronal angular velocities were significantly correlated with the knee abduction moment (R of 0.28-0.51), which is a strong indicator of ACL injury risk. This study suggested that the thigh and shank angular velocities, which describe the angular dynamics of the movement, should be considered in future studies about ACL injury mechanisms.

Dynamics of success and failure in phage and antibiotic therapy in experimental infections.

PubMed

Bull, J J; Levin, Bruce R; DeRouin, Terry; Walker, Nina; Bloch, Craig A

2002-11-26

In 1982 Smith and Huggins showed that bacteriophages could be at least as effective as antibiotics in preventing mortality from experimental infections with a capsulated E. coli (K1) in mice. Phages that required the K1 capsule for infection were more effective than phages that did not require this capsule, but the efficacies of phages and antibiotics in preventing mortality both declined with time between infection and treatment, becoming virtually ineffective within 16 hours. We develop quantitative microbiological procedures that (1) explore the in vivo processes responsible for the efficacy of phage and antibiotic treatment protocols in experimental infections (the Resistance Competition Assay, or RCA), and (2) survey the therapeutic potential of phages in vitro (the Phage Replication Assay or PRA). We illustrate the application and utility of these methods in a repetition of Smith and Huggins' experiments, using the E. coli K1 mouse thigh infection model, and applying treatments of phages or streptomycin. 1) The Smith and Huggins phage and antibiotic therapy results are quantitatively and qualitatively robust. (2) Our RCA values reflect the microbiological efficacies of the different phages and of streptomycin in preventing mortality, and reflect the decline in their efficacy with a delay in treatment. These results show specifically that bacteria become refractory to treatment over the term of infection. (3) The K1-specific and non-specific phages had similar replication rates on bacteria grown in broth (based on the PRA), but the K1-specific phage had markedly greater replication rates in mouse serum.

A Lung Segmental Model of Chronic Pseudomonas Infection in Sheep

PubMed Central

Collie, David; Govan, John; Wright, Steven; Thornton, Elisabeth; Tennant, Peter; Smith, Sionagh; Doherty, Catherine; McLachlan, Gerry

2013-01-01

Background Chronic lung infection with Pseudomonas aeruginosa is a major contributor to morbidity, mortality and premature death in cystic fibrosis. A new paradigm for managing such infections is needed, as are relevant and translatable animal models to identify and test concepts. We sought to improve on limitations associated with existing models of infection in small animals through developing a lung segmental model of chronic Pseudomonas infection in sheep. Methodology/Principal Findings Using local lung instillation of P. aeruginosa suspended in agar beads we were able to demonstrate that such infection led to the development of a suppurative, necrotising and pyogranulomatous pneumonia centred on the instilled beads. No overt evidence of organ or systemic compromise was apparent in any animal during the course of infection. Infection persisted in the lungs of individual animals for as long as 66 days after initial instillation. Quantitative microbiology applied to bronchoalveolar lavage fluid derived from infected segments proved an insensitive index of the presence of significant infection in lung tissue (>104 cfu/g). Conclusions/Significance The agar bead model of chronic P. aeruginosa lung infection in sheep is a relevant platform to investigate both the pathobiology of such infections as well as novel approaches to their diagnosis and therapy. Particular ethical benefits relate to the model in terms of refining existing approaches by compromising a smaller proportion of the lung with infection and facilitating longitudinal assessment by bronchoscopy, and also potentially reducing animal numbers through facilitating within-animal comparisons of differential therapeutic approaches. PMID:23874438

Inbred guinea pig model of intrauterine infection with cytomegalovirus.

PubMed

Griffith, B P; McCormick, S R; Booss, J; Hsiung, G D

1986-01-01

Outbred guinea pigs have previously been utilized in an experimental model for the study of congenital infection with cytomegalovirus (CMV). Development of an inbred model of intrauterine CMV infection would allow analysis of the cells involved in CMV immunity, studies of transplacental CMV transfer, and investigation of the cellular immune factors that participate in intrauterine CMV infections. This study was therefore designed to assess the inbred guinea pig as a model for the study of congenital CMV infection. Intrauterine fetal and placental infection with CMV was demonstrated in inbred Strain 2 guinea pigs, and the maternal factors influencing transplacental transmission of CMV were evaluated. Infectious virus was recovered from placentas and offspring of mothers that experienced primary CMV infection during pregnancy, but not from placentas and offspring of mothers that were inoculated with CMV prior to pregnancy. However, histologic lesions consisting of focal necrosis and inflammation were seen in tissues of offspring from both groups of mothers. Inoculation of seronegative pregnant Strain 2 animals with low doses of virus (2.5 to 3.5 log10 TCID50) resulted in both placental and fetal CMV infection without significant maternal death. Infection of placentas and offspring occurred in utero regardless of the stage of pregnancy. In addition, infectious virus was detectable in fetal tissues at the time of maternal viremia but also later during the course of maternal infection, ie, 4 weeks after inoculation. These findings indicate that the inbred guinea pig model can be used to investigate the pathogenesis of intrauterine CMV infections.

Model systems for the study of Enterococcal colonization and infection

PubMed Central

Goh, H. M. Sharon; Yong, M. H. Adeline; Chong, Kelvin Kian Long

2017-01-01

ABSTRACT Enterococcus faecalis and Enterococcus faecium are common inhabitants of the human gastrointestinal tract, as well as frequent opportunistic pathogens. Enterococci cause a range of infections including, most frequently, infections of the urinary tract, catheterized urinary tract, bloodstream, wounds and surgical sites, and heart valves in endocarditis. Enterococcal infections are often biofilm-associated, polymicrobial in nature, and resistant to antibiotics of last resort. Understanding Enterococcal mechanisms of colonization and pathogenesis are important for identifying new ways to manage and intervene with these infections. We review vertebrate and invertebrate model systems applied to study the most common E. faecalis and E. faecium infections, with emphasis on recent findings examining Enterococcal-host interactions using these models. We discuss strengths and shortcomings of each model, propose future animal models not yet applied to study mono- and polymicrobial infections involving E. faecalis and E. faecium, and comment on the significance of anti-virulence strategies derived from a fundamental understanding of host-pathogen interactions in model systems. PMID:28102784

Two anthrax cases with soft tissue infection, severe oedema and sepsis in Danish heroin users

PubMed Central

2013-01-01

Background Anthrax had become extremely rare in Europe, but in 2010 an outbreak of anthrax among heroin users in Scotland increased awareness of contaminated heroin as a source of anthrax. We present the first two Danish cases of injectional anthrax and discuss the clinical presentations, which included both typical and more unusual manifestations. Case presentations The first patient, a 55-year old man with HIV and hepatitis C virus co-infection, presented with severe pain in the right thigh and lower abdomen after injecting heroin into the right groin. Computed tomography and ultrasonographic examination of the abdomen and right thigh showed oedematous thickened peritoneum, distended oedematous mesentery and subcutaneous oedema of the right thigh. At admission the patient was afebrile but within 24 hours he progressed to severe septic shock and abdominal compartment syndrome. Cultures of blood and intraperitoneal fluid grew Bacillus anthracis. The patient was treated with meropenem, clindamycin, ciprofloxacin and metronidazole. Despite maximum supportive care including mechanical ventilation, vasopressor treatment and continuous veno-venous hemodiafiltration the patient died on day four. The second patient, a 39-year old man with chronic hepatitis C virus infection, presented with fever and a swollen right arm after injecting heroin into his right arm. The arm was swollen from the axilla to the wrist with tense and discoloured skin. He was initially septic with low blood pressure but responded to crystalloids. During the first week, swelling progressed and the patient developed massive generalised oedema with a weight gain of 40 kg. When blood cultures grew Bacillus anthracis antibiotic treatment was changed to meropenem, moxifloxacin and metronidazole, and on day 7 hydroxycloroquin was added. The patient responded to treatment and was discharged after 29 days. Conclusions These two heroin-associated anthrax cases from Denmark corroborate that heroin contaminated

Two anthrax cases with soft tissue infection, severe oedema and sepsis in Danish heroin users.

PubMed

Russell, Lene; Pedersen, Michael; Jensen, Andreas V; Søes, Lillian Marie; Hansen, Ann-Brit Eg

2013-09-03

Anthrax had become extremely rare in Europe, but in 2010 an outbreak of anthrax among heroin users in Scotland increased awareness of contaminated heroin as a source of anthrax. We present the first two Danish cases of injectional anthrax and discuss the clinical presentations, which included both typical and more unusual manifestations. The first patient, a 55-year old man with HIV and hepatitis C virus co-infection, presented with severe pain in the right thigh and lower abdomen after injecting heroin into the right groin. Computed tomography and ultrasonographic examination of the abdomen and right thigh showed oedematous thickened peritoneum, distended oedematous mesentery and subcutaneous oedema of the right thigh. At admission the patient was afebrile but within 24 hours he progressed to severe septic shock and abdominal compartment syndrome. Cultures of blood and intraperitoneal fluid grew Bacillus anthracis. The patient was treated with meropenem, clindamycin, ciprofloxacin and metronidazole. Despite maximum supportive care including mechanical ventilation, vasopressor treatment and continuous veno-venous hemodiafiltration the patient died on day four.The second patient, a 39-year old man with chronic hepatitis C virus infection, presented with fever and a swollen right arm after injecting heroin into his right arm. The arm was swollen from the axilla to the wrist with tense and discoloured skin. He was initially septic with low blood pressure but responded to crystalloids. During the first week, swelling progressed and the patient developed massive generalised oedema with a weight gain of 40 kg. When blood cultures grew Bacillus anthracis antibiotic treatment was changed to meropenem, moxifloxacin and metronidazole, and on day 7 hydroxycloroquin was added. The patient responded to treatment and was discharged after 29 days. These two heroin-associated anthrax cases from Denmark corroborate that heroin contaminated with anthrax spores may be a continuous

Stability of differential susceptibility and infectivity epidemic models

PubMed Central

Bonzi, B.; Fall, A. A.; Iggidr, Abderrahman; Sallet, Gauthier

2011-01-01

We introduce classes of differential susceptibility and infectivity epidemic models. These models address the problem of flows between the different susceptible, infectious and infected compartments and differential death rates as well. We prove the global stability of the disease free equilibrium when the basic reproduction ratio ≤ 1 and the existence and uniqueness of an endemic equilibrium when > 1. We also prove the global asymptotic stability of the endemic equilibrium for a differential susceptibility and staged progression infectivity model, when > 1. Our results encompass and generalize those of [18, 22]. AMS Subject Classification : 34A34,34D23,34D40,92D30 PMID:20148330

A micro-epidemic model for primary dengue infection

NASA Astrophysics Data System (ADS)

Mishra, Arti; Gakkhar, Sunita

2017-06-01

In this paper, a micro-epidemic non-linear dynamical model has been proposed and analyzed for primary dengue infection. The model incorporates the effects of T cells immune response as well as humoral response during pathogenesis of dengue infection. The time delay has been accounted for production of antibodies from B cells. The basic reproduction number (R0) has been computed. Three equilibrium states are obtained. The existence and stability conditions for infection-free and ineffective cellular immune response state have been discussed. The conditions for existence of endemic state have been obtained. Further, the parametric region is obtained where system exhibits complex behavior. The threshold value of time delay has been computed which is critical for change in stability of endemic state. A threshold level for antibodies production rate has been obtained over which the infection will die out even though R0 > 1. The model is in line with the clinical observation that viral load decreases within 7-14 days from the onset of primary infection.

Tracking vaginal, anal and oral infection in a mouse papillomavirus infection model.

PubMed

Hu, Jiafen; Budgeon, Lynn R; Cladel, Nancy M; Balogh, Karla; Myers, Roland; Cooper, Timothy K; Christensen, Neil D

2015-12-01

Noninvasive and practical techniques to longitudinally track viral infection are sought after in clinical practice. We report a proof-of-principle study to monitor the viral DNA copy number using a newly established mouse papillomavirus (MmuPV1) mucosal infection model. We hypothesized that viral presence could be identified and quantified by collecting lavage samples from cervicovaginal, anal and oral sites. Nude mice infected at these sites with infectious MmuPV1 were tracked for up to 23 weeks starting at 6 weeks post-infection. Viral DNA copy number was determined by SYBR Green Q-PCR analysis. In addition, we tracked viral DNA load through three complete oestrous cycles to pinpoint whether there was a correlation between the DNA load and the four stages of the oestrous cycle. Our results showed that high viral DNA copy number was reproducibly detected from both anal and cervicovaginal lavage samples. The infection and disease progression were further confirmed by histology, cytology, in situ hybridization, immunohistochemistry and transmission electron microscopy. Interestingly, the viral copy number fluctuated over the oestrous cycle, with the highest level at the oestrus stage, implying that multiple sampling might be necessary to provide a reliable diagnosis. Virus DNA was detected in oral lavage samples at a later time after infection. Lower viral DNA load was found in oral samples when compared with those in anal and vaginal tracts. To our knowledge, our study is the first in vivo study to sequentially monitor papillomavirus infection from mucosal anal, oral and vaginal tracts in a preclinical model.

Compartment syndrome of the thigh complicating surgical treatment of ipsilateral femur and ankle fractures

NASA Technical Reports Server (NTRS)

Moore, M. R.; Garfin, S. R.; Hargens, A. R.

1987-01-01

A 26-year-old man presented with ipsilateral femur and ankle fractures. The patient was treated with interlocking nail of his femur fracture, followed by open reduction and internal fixation of his ankle fracture under tourniquet control. Postoperatively, the patient developed compartment syndrome of his thigh with elevated pressures, requiring decompressive fasciotomies. This case illustrates the possible complication of treating a femur fracture with intramedullary nailing and then immediately applying a tourniquet to treat an ipsilateral extremity fracture. Because of the complication with this patient, we feel the procedure should be staged, or a tourniquet should be avoided if possible.

MRI assessment of the thigh musculature in dermatomyositis and healthy subjects using diffusion tensor imaging, intravoxel incoherent motion and dynamic DTI.

PubMed

Sigmund, E E; Baete, S H; Luo, T; Patel, K; Wang, D; Rossi, I; Duarte, A; Bruno, M; Mossa, D; Femia, A; Ramachandran, S; Stoffel, D; Babb, J S; Franks, A; Bencardino, J

2018-06-04

Dermatomyositis (DM) is an idiopathic inflammatory myopathy involving severe debilitation in need of diagnostics. We evaluated the proximal lower extremity musculature with diffusion tensor imaging (DTI), intravoxel incoherent motion (IVIM) and dynamic DTI in DM patients and controls and compared with standard clinical workup.  METHODS: In this IRB-approved, HIPAA-compliant study with written informed consent, anatomical, Dixon fat/water and diffusion imaging were collected in bilateral thigh MRI of 22 controls and 27 DM patients in a 3T scanner. Compartments were scored on T1/T2 scales. Single voxel dynamic DTI metrics in quadriceps before and after 3-min leg exercise were measured. Spearman rank correlation and mixed model analysis of variance/covariance (ANOVA/ANCOVA) were used to correlate with T1 and T2 scores and to compare patients with controls. DM patients showed significantly lower pseudo-diffusion and volume in quadriceps than controls. All subjects showed significant correlation between T1 score and signal-weighted fat fraction; tissue diffusion and pseudo-diffusion varied significantly with T1 and T2 score in patients. Radial and mean diffusion exercise response in patients was significantly higher than controls. Static and dynamic diffusion imaging metrics show correlation with conventional imaging scores, reveal spatial heterogeneity, and provide means to differentiate dermatomyositis patients from controls. • Diffusion imaging shows regional differences between thigh muscles of dermatomyositis patients and controls. • Signal-weighted fat fraction and diffusion metrics correlate with T1/T2 scores of disease severity. • Dermatomyositis patients show significantly higher radial diffusion exercise response than controls.

Relationship between power-duration parameters and mechanical and anthropometric properties of the thigh in elite cyclists.

PubMed

Kordi, Mehdi; Menzies, Campbell; Parker Simpson, Len

2018-03-01

The curvature constant (W') and asymptote (critical power; CP) of the power-duration relationship are important parameters for explaining cycling performance. Short-duration endurance cycling events rely more heavily on the W'; however, the full mechanistic underpinning of this parameter is yet to be determined. Evidence suggests both muscle volume and muscle strength may contribute to the magnitude of W'. Therefore, the present study investigated the relationship between power-duration parameters (CP and W') and (1) anthropometric and (2) mechanical properties of thigh muscles in a sample of elite cyclists. Eleven elite male cyclists had gross thigh volume (T VOL ), quadriceps muscle volume (Q VOL ), vastus lateralis (VL) muscle pennation angle (PA) and VL muscle thickness (MT) measured. Additionally, maximum torque production of the knee extensors (F MAX ) was assessed. The relationship between these anthropometric and mechanical measures and both the CP and W' were determined. W' showed a very strong positive and significant relationship with F MAX (r = 0.87, p < 0.001) and a large positive and significant relationship with T VOL (r = 0.60, p =  0.05). No other anthropometric characteristics were related to the W'. The CP was not associated with any mechanical or anthropometric parameter. In addition to muscle size, the maximal evocable force of a muscle (group) appears to be linked to the magnitude of the W' in elite cyclists.

Comparison Thigh Skeletal Muscles between Snowboarding Halfpipe Athletes and Healthy Volunteers Using Quantitative Multi-Parameter Magnetic Resonance Imaging at Rest.

PubMed

Sun, He; Xu, Meng-Tao; Wang, Xiao-Qi; Wang, Meng-Hu; Wang, Bao-Heng; Wang, Feng-Zhe; Pan, Shi-Nong

2018-05-05

Magnetic resonance (MR) imaging provides a unique, noninvasive diagnostic platform to quantify the physiological and biochemical variables of skeletal muscle at rest. This study was to investigate the difference in thigh skeletal muscles between snowboarding halfpipe athletes and healthy volunteers via multiparametric MR imaging. A comparative study was conducted between 12 healthy volunteers and 14 snowboarding halfpipe athletes. MR scanning targeted the left leg at the level of the proximal thigh on a 3.0T MR system. The measured parameters compared between the two groups included T1, T2, T2* relaxation times, fat fraction (FF), and cross-sectional area (CSA) of the quadriceps femoris and the hamstring muscles. Statistical analysis was carried out using independent sample t-test. Interrater reliability was also assessed with intraclass correlation coefficients (ICCs). It was statistically equivalent between two groups in age, body mass index, thigh circumference, calf circumference, systolic blood pressure, and resting heart rate (all P > 0.05). However, the T1 and T2 values of the hamstring muscles in the athlete group were found to be significantly shorter than those in control group (T1: 1063.3 ± 24.1 ms vs. 1112.0 ± 38.2 ms in biceps femoris, 1050.4 ± 31.2 ms vs. 1095.0 ± 39.5 ms in semitendinosus, 1053.1 ± 31.7 ms vs. 1118.4 ± 40.0 ms in semimembranosus, respectively; T2: 33.4 ± 0.7 ms vs. 36.1 ± 1.9 ms in biceps femoris, 34.6 ± 2.0 ms vs. 37.0 ± 1.9 ms in semitendinosus, 36.9 ± 1.5 ms vs. 38.9 ± 2.4 ms in semimembranosus, respectively; all P < 0.05) although T2* relaxation time was detected with no significant difference. The FF of the hamstring muscles was obviously less than the control group (5.5 ± 1.9% vs. 10.7 ± 4.7%, P < 0.001). In addition, the quadriceps' CSA in the athlete group was substantially larger than the control group (8039.0 ± 1072.3 vs. 6258.2 ± 852.0 mm 2 , P < 0.001). Interrater reliability was excellent (ICC: 0

Effectiveness of netilmicin and tobramycin against Pseudomonas aeruginosa in vitro and in an experimental tissue infection in mice.

PubMed

Moffie, B G; Hoogeterp, J J; Lim, T; Douwes-Idema, A E; Mattie, H

1993-03-01

The activity of netilmicin and tobramycin against Pseudomonas aeruginosa was assessed in vitro in the presence of constant and exponentially declining concentrations, and in mice in an experimental thigh infection. The activity in vitro at constant concentrations was expressed as the maximal killing rate (ER) during 3 h of exposure. On the basis of the quantitative relation between E(R) and the drug concentration, the numbers of cfu expected at consecutive times, at constant as well as at declining concentrations, were predicted. The relationship between observed numbers and predicted values of ERt were similar under both conditions for both drugs. On the same basis the numbers of cfu expected in the experimental thigh infection were predicted. There was indeed a significant linear relationship between observed numbers of cfu in homogenized muscle and the values predicted on the basis of the pharmacokinetics of the aminoglycosides, but the slope of this relationship was only 0.22. There was no difference in this respect between the two antibiotics. It is concluded that the efficacy of netilmicin and tobramycin against P. aeruginosa is considerably less in vivo than in vitro, but the relation is about the same for the two drugs; therefore the slightly higher activity of tobramycin in vitro is relevant in the in-vivo situation.

Interpretations and pitfalls in modelling vector-transmitted infections.

PubMed

Amaku, M; Azevedo, F; Burattini, M N; Coutinho, F A B; Lopez, L F; Massad, E

2015-07-01

In this paper we propose a debate on the role of mathematical models in evaluating control strategies for vector-borne infections. Mathematical models must have their complexity adjusted to their goals, and we have basically two classes of models. At one extreme we have models that are intended to check if our intuition about why a certain phenomenon occurs is correct. At the other extreme, we have models whose goals are to predict future outcomes. These models are necessarily very complex. There are models in between these classes. Here we examine two models, one of each class and study the possible pitfalls that may be incurred. We begin by showing how to simplify the description of a complicated model for a vector-borne infection. Next, we examine one example found in a recent paper that illustrates the dangers of basing control strategies on models without considering their limitations. The model in this paper is of the second class. Following this, we review an interesting paper (a model of the first class) that contains some biological assumptions that are inappropriate for dengue but may apply to other vector-borne infections. In conclusion, we list some misgivings about modelling presented in this paper for debate.

Measures of functional performance and their association with hip and thigh strength.

PubMed

Kollock, Roger; Van Lunen, Bonnie L; Ringleb, Stacie I; Oñate, James A

2015-01-01

Insufficient hip and thigh strength may increase an athlete's susceptibility to injury. However, screening for strength deficits using isometric and isokinetic instrumentation may not be practical in all clinical scenarios. To determine if functional performance tests are valid indicators of hip and thigh strength. Descriptive laboratory study. Research laboratory. Sixty-two recreationally athletic men (n = 30, age = 21.07 years, height = 173.84 cm, mass = 81.47 kg) and women (n = 32, age = 21.03 years, height = 168.77 cm, mass = 68.22 kg) participants were recruited. During session 1, we measured isometric peak force and rate of force development for 8 lower extremity muscle groups, followed by an isometric endurance test. During session 2, participants performed functional performance tests. Peak force, rate of force development, fatigue index, hop distance (or height), work (joules), and number of hops performed during the 30-second lateral-hop test were assessed. The r values were squared to calculate r (2). We used Pearson correlations to evaluate the associations between functional performance and strength. In men, the strongest relationship was observed between triple-hop work and hip-adductor peak force (r(2) = 50, P ≤ .001). Triple-hop work also was related to hip-adductor (r(2) = 38, P ≤ .01) and hip-flexor (r(2) = 37, P ≤ .01) rate of force development. For women, the strongest relationships were between single-legged vertical-jump work and knee-flexor peak force (r(2) = 0.44, P ≤ .01) and single-legged vertical-jump height and knee-flexor peak force (r(2) = 0.42, P ≤ .01). Single-legged vertical-jump height also was related to knee-flexor rate of force development (r(2) = 0.49, P ≤ .001). The 30-second lateral-hop test did not account for a significant portion of the variance in strength endurance. Hop tests alone did not provide clinicians with enough information to make evidence-based decisions about lower extremity strength in isolated

Vaccination Programs for Endemic Infections: Modelling Real versus Apparent Impacts of Vaccine and Infection Characteristics

NASA Astrophysics Data System (ADS)

Ragonnet, Romain; Trauer, James M.; Denholm, Justin T.; Geard, Nicholas L.; Hellard, Margaret; McBryde, Emma S.

2015-10-01

Vaccine effect, as measured in clinical trials, may not accurately reflect population-level impact. Furthermore, little is known about how sensitive apparent or real vaccine impacts are to factors such as the risk of re-infection or the mechanism of protection. We present a dynamic compartmental model to simulate vaccination for endemic infections. Several measures of effectiveness are calculated to compare the real and apparent impact of vaccination, and assess the effect of a range of infection and vaccine characteristics on these measures. Although broadly correlated, measures of real and apparent vaccine effectiveness can differ widely. Vaccine impact is markedly underestimated when primary infection provides partial natural immunity, when coverage is high and when post-vaccination infectiousness is reduced. Despite equivalent efficacy, ‘all or nothing’ vaccines are more effective than ‘leaky’ vaccines, particularly in settings with high risk of re-infection and transmissibility. Latent periods result in greater real impacts when risk of re-infection is high, but this effect diminishes if partial natural immunity is assumed. Assessments of population-level vaccine effects against endemic infections from clinical trials may be significantly biased, and vaccine and infection characteristics should be considered when modelling outcomes of vaccination programs, as their impact may be dramatic.

Vaccination Programs for Endemic Infections: Modelling Real versus Apparent Impacts of Vaccine and Infection Characteristics

PubMed Central

Ragonnet, Romain; Trauer, James M.; Denholm, Justin T.; Geard, Nicholas L.; Hellard, Margaret; McBryde, Emma S.

2015-01-01

Vaccine effect, as measured in clinical trials, may not accurately reflect population-level impact. Furthermore, little is known about how sensitive apparent or real vaccine impacts are to factors such as the risk of re-infection or the mechanism of protection. We present a dynamic compartmental model to simulate vaccination for endemic infections. Several measures of effectiveness are calculated to compare the real and apparent impact of vaccination, and assess the effect of a range of infection and vaccine characteristics on these measures. Although broadly correlated, measures of real and apparent vaccine effectiveness can differ widely. Vaccine impact is markedly underestimated when primary infection provides partial natural immunity, when coverage is high and when post-vaccination infectiousness is reduced. Despite equivalent efficacy, ‘all or nothing’ vaccines are more effective than ‘leaky’ vaccines, particularly in settings with high risk of re-infection and transmissibility. Latent periods result in greater real impacts when risk of re-infection is high, but this effect diminishes if partial natural immunity is assumed. Assessments of population-level vaccine effects against endemic infections from clinical trials may be significantly biased, and vaccine and infection characteristics should be considered when modelling outcomes of vaccination programs, as their impact may be dramatic. PMID:26482413

A model of immunomodulatory for dengue infection mm

NASA Astrophysics Data System (ADS)

Zulfa, Annisa; Handayani, Dewi; Nuraini, Nuning

2018-03-01

An immunomodulatory model for dengue infection is constructed in this paper. This study focuses on T-cell compartments and B cells that are immune cells involved in the dengue infection process. Dengue virus-infected monocyte cells release interferons to signal T-cells to activate B-cells and produce antibodies. Immunomodulator acts as a treatment control and aims to increase the numbers of antibodies so it is expected to reduce the number of infected monocyte cells by dengue virus. Numerical simulation shows that the greater the rate of f (t) the immune cells will be stimulated to suppress the number of infected cells.

Modeling tuberculosis pathogenesis through ex vivo lung tissue infection.

PubMed

Carranza-Rosales, Pilar; Carranza-Torres, Irma Edith; Guzmán-Delgado, Nancy Elena; Lozano-Garza, Gerardo; Villarreal-Treviño, Licet; Molina-Torres, Carmen; Villarreal, Javier Vargas; Vera-Cabrera, Lucio; Castro-Garza, Jorge

2017-12-01

Tuberculosis (TB) is one of the top 10 causes of death worldwide. Several in vitro and in vivo experimental models have been used to study TB pathogenesis and induction of immune response during Mycobacterium tuberculosis infection. Precision cut lung tissue slices (PCLTS) is an experimental model, in which all the usual cell types of the organ are found, the tissue architecture and the interactions amongst the different cells are maintained. PCLTS in good physiological conditions, monitored by MTT assay and histology, were infected with either virulent Mycobacterium tuberculosis strain H37Rv or the TB vaccine strain Mycobacterium bovis BCG. Histological analysis showed that bacilli infecting lung tissue slices were observed in the alveolar septa, alveolar light spaces, near to type II pneumocytes, and inside macrophages. Mycobacterial infection of PCLTS induced TNF-α production, which is consistent with previous M. tuberculosis in vitro and in vivo studies. This is the first report of using PCLTS as a system to study M. tuberculosis infection. The PCLTS model provides a useful tool to evaluate the innate immune responses and other aspects during the early stages of mycobacterial infection. Copyright © 2017. Published by Elsevier Ltd.

Tetraodon nigroviridis: A model of Vibrio parahaemolyticus infection.

PubMed

Peng, Wan; Shi, Yu; Li, Gao-Fei; He, Liang-Ge; Liang, Yao-Si; Zhang, Yong; Zhou, Li-Bin; Lin, Hao-Ran; Lu, Dan-Qi

2016-09-01

Vibriosis is the most common bacterial diseases and brings great economic loss on aquaculture. Vibrio parahaemolyticus (V. parahaemolyticus), a gram-negative bacterium, has been identified as one main pathogens of Vibriosis. The pathogenic mechanism of V. parahaemolyticus is not entirely clear now. In our study, a model of V. parahaemolyticus infection of green-spotted puffer fish (Tetraodon nigroviridis) was established. T. nigroviridis were injected intraperitoneally (i.p.) with 200 μL of V. parahaemolyticus (8 × 10(10) CFU/mL). V. parahaemolyticus infection caused 64% mortality and infected some organs of T. nigroviridis. Histopathology studies revealed V. parahaemolyticus infection induced tissue structural changes, including adipose hollow space in the liver. Immunohistochemistry showed V. parahaemolyticus were present in infected tissue such as liver, head kidney and spleen. In livers of T. nigroviridis infected by V. parahaemolyticus, the alkaline phosphatases (ALP) activity first gradually increased and then backed to normal level, a trend that was on the contrary to the expression profile of the miR-29b. Quantitative real-time PCR analysis showed that the expression level of TLR1, TLR2, TLR5, TLR9, TLR21, NOD1, NOD2 and IL-6 in response to V. parahaemolyticus infection decreased compared to that of non-infected fish. The establishment of the T. nigroviridis model of V. parahaemolyticus infection further confirmed V. parahaemolyticus spreads through the blood circulation system primary as an extracellular pathogen. Meanwhile, liver is an important target organ when infected by V. parahaemolyticus. miR-29b in liver was involved in the progress of liver steatosis during V. parahaemolyticus infection. Moreover, V. parahaemolyticus infection in vivo may have an effect of immunosuppression on host. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dynamics of a Class of HIV Infection Models with Cure of Infected Cells in Eclipse Stage.

PubMed

Maziane, Mehdi; Lotfi, El Mehdi; Hattaf, Khalid; Yousfi, Noura

2015-12-01

In this paper, we propose two HIV infection models with specific nonlinear incidence rate by including a class of infected cells in the eclipse phase. The first model is described by ordinary differential equations (ODEs) and generalizes a set of previously existing models and their results. The second model extends our ODE model by taking into account the diffusion of virus. Furthermore, the global stability of both models is investigated by constructing suitable Lyapunov functionals. Finally, we check our theoretical results with numerical simulations.

Thigh muscle and subcutaneous tissue thickness measured using ultrasound imaging in older females living in extended care: a preliminary study.

PubMed

Welch, Daniella; Ndanyo, Laetitia Sungu; Brown, Simon; Agyapong-Badu, Sandra; Warner, Martin; Stokes, Maria; Samuel, Dinesh

2018-05-01

Thigh tissue thickness has not been examined in older females living in extended care in UK as an indicator of musculoskeletal health. This study examined the feasibility of using ultrasound imaging to measure the thickness of superficial (fat) and deep layers (muscle) of the thigh in older females living in extended care. In ten older females in extended care (aged 80-98 years, mean 88 ± 6.8; body mass: 56.5 ± 12.6 kg) images of the anterior thigh (dominant) were taken in supine using B-mode ultrasound imaging. Superficial and deep layers were measured and percentage thickness was calculated. Independent t tests compared data from those in extended care to ten sedentary females living independently (aged 80-90 years, mean 84 ± 3.6; body mass: 61.6 ± 10.0 kg). Thickness of the superficial layers was not significantly different between the two groups (CI -0.017 to 0.815, p = 0.059). However, those living in extended care had greater (p < 0.001) muscle thickness (mean 2.75 ± 0.48 cm) than those living independently (mean 1.83 ± 0.3 cm), which was similarly significant when normalised for body mass (extended care 0.51 ± 0.16; independent living 0.30 ± 0.06). These novel findings showed it is feasible to use ultrasound to measure muscles in older females in extended care and that muscle thickness was larger than in those living independently. The reason for the difference seen between groups would need to be confirmed by a larger study that also examined factors related to risk of sarcopenia and frailty, such as nutrition and physical activity levels.

Visually induced analgesia in a deep tissue experimental pain model: A randomised crossover experiment.

PubMed

van Selm, M J; Gibson, W I; Travers, M J; Moseley, G L; Hince, D; Wand, B M

2018-04-20

Visualizing one's own painful body part appears to have an effect on reported pain intensity. Furthermore, it seems that manipulating the size of the viewed image can determine the direction and extent of this phenomenon. When visual distortion has been applied to clinical populations, the analgesic effects have been in opposition to those observed in some experimental pain models. To help resolve this problem, we explored the effect of visualisation and magnification of the visual image on reported pain using a delayed onset muscle soreness (DOMS) pain model. We induced DOMS in the quadriceps of 20 healthy volunteers. Forty-eight hours later, participants performed a series of painful contractions of the DOMS-affected muscle under four randomised conditions: (1) Viewing the injured thigh; (2) Viewing the contralateral thigh; (3) Viewing a neutral object; and (4) Viewing the injured thigh through magnifying glasses. For each condition, participants rated their pain intensity during a series of painful contractions. We observed that direct visualisation of the injured thigh had no effect on pain intensity when compared to viewing the contralateral thigh or neutral object. However, magnification of the DOMS-affected leg during the performance of painful contractions caused participants to report more pain than when viewing the injured thigh normally. These results further demonstrate that the effect of visualisation varies between different pain conditions. These results may have implications for the integration of visual feedback into clinical practice. We present delayed onset muscle soreness as a model for exploring visually induced analgesia. Our findings suggest that this phenomenon is expressed differently in exogenous and endogenous experimental pain models. Further exploration may offer a potential pathway for the integration of visual analgesia into the management of clinical pain. © 2018 European Pain Federation - EFIC®.

Lean muscle volume of the thigh has a stronger relationship with muscle power than muscle strength in women with knee osteoarthritis.

PubMed

Davison, Michael J; Maly, Monica R; Keir, Peter J; Hapuhennedige, Sandani M; Kron, Amie T; Adachi, Jonathan D; Beattie, Karen A

2017-01-01

Thigh lean muscle and intramuscular fat have been implicated in the impairment of physical function observed in people with knee osteoarthritis. We investigated the relationships of quadriceps and hamstrings intramuscular fat fraction and lean muscle volume with muscle power and strength, controlling for neuromuscular activation, and physical performance in women with knee OA. Women (n=20) 55years or older with symptomatic, radiographic knee osteoarthritis underwent a 3.0T magnetic resonance imaging scan of the thigh of their most symptomatic knee. Axial fat-separated images were analyzed using software to quantify intramuscular fat and lean muscle volumes of the quadriceps and hamstrings. To quantify strength and power of the knee extensors and flexors, participants performed maximum voluntary isometric contraction and isotonic knee extensions and flexions, respectively. Electromyography of the quadriceps and hamstrings was measured. Participants also completed five physical performance tests. Quadriceps and hamstrings lean muscle volumes were related to isotonic knee extensor (B=0.624; p=0.017) and flexor (B=1.518; p=0.032) power, but not knee extensor (B=0.001; p=0.615) or flexor (B=0.001; p=0.564) isometric strength. Intramuscular fat fractions were not related to isotonic knee extensor or flexor power, nor isometric strength. No relationships were found between intramuscular fat or lean muscle volume and physical performance. Muscle power may be more sensitive than strength to lean muscle mass in women with knee osteoarthritis. Thigh lean muscle mass, but neither intramuscular nor intermuscular fat, is related to knee extensor and flexor power in women with knee osteoarthritis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Approximate analytical modeling of leptospirosis infection

NASA Astrophysics Data System (ADS)

Ismail, Nur Atikah; Azmi, Amirah; Yusof, Fauzi Mohamed; Ismail, Ahmad Izani

2017-11-01

Leptospirosis is an infectious disease carried by rodents which can cause death in humans. The disease spreads directly through contact with feces, urine or through bites of infected rodents and indirectly via water contaminated with urine and droppings from them. Significant increase in the number of leptospirosis cases in Malaysia caused by the recent severe floods were recorded during heavy rainfall season. Therefore, to understand the dynamics of leptospirosis infection, a mathematical model based on fractional differential equations have been developed and analyzed. In this paper an approximate analytical method, the multi-step Laplace Adomian decomposition method, has been used to conduct numerical simulations so as to gain insight on the spread of leptospirosis infection.

Marek's disease virus infection of phagocytes: a de novo in vitro infection model.

PubMed

Chakraborty, Pankaj; Vervelde, Lonneke; Dalziel, Robert G; Wasson, Peter S; Nair, Venugopal; Dutia, Bernadette M; Kaiser, Pete

2017-05-01

Marek's disease virus (MDV) is an alphaherpesvirus that induces T-cell lymphomas in chickens. Natural infections in vivo are caused by the inhalation of infected poultry house dust and it is presumed that MDV infection is initiated in the macrophages from where the infection is passed to B cells and activated T cells. Virus can be detected in B and T cells and macrophages in vivo, and both B and T cells can be infected in vitro. However, attempts to infect macrophages in vitro have not been successful. The aim of this study was to develop a model for infecting phagocytes [macrophages and dendritic cells (DCs)] with MDV in vitro and to characterize the infected cells. Chicken bone marrow cells were cultured with chicken CSF-1 or chicken IL-4 and chicken CSF-2 for 4 days to produce macrophages and DCs, respectively, and then co-cultured with FACS-sorted chicken embryo fibroblasts (CEFs) infected with recombinant MDV expressing EGFP. Infected phagocytes were identified and sorted by FACS using EGFP expression and phagocyte-specific mAbs. Detection of MDV-specific transcripts of ICP4 (immediate early), pp38 (early), gB (late) and Meq by RT-PCR provided evidence for MDV replication in the infected phagocytes. Time-lapse confocal microscopy was also used to demonstrate MDV spread in these cells. Subsequent co-culture of infected macrophages with CEFs suggests that productive virus infection may occur in these cell types. This is the first report of in vitro infection of phagocytic cells by MDV.

Dynamics of a stochastic HIV-1 infection model with logistic growth

NASA Astrophysics Data System (ADS)

Jiang, Daqing; Liu, Qun; Shi, Ningzhong; Hayat, Tasawar; Alsaedi, Ahmed; Xia, Peiyan

2017-03-01

This paper is concerned with a stochastic HIV-1 infection model with logistic growth. Firstly, by constructing suitable stochastic Lyapunov functions, we establish sufficient conditions for the existence of ergodic stationary distribution of the solution to the HIV-1 infection model. Then we obtain sufficient conditions for extinction of the infection. The stationary distribution shows that the infection can become persistent in vivo.

Modeling malaria and typhoid fever co-infection dynamics.

PubMed

Mutua, Jones M; Wang, Feng-Bin; Vaidya, Naveen K

2015-06-01

Malaria and typhoid are among the most endemic diseases, and thus, of major public health concerns in tropical developing countries. In addition to true co-infection of malaria and typhoid, false diagnoses due to similar signs and symptoms and false positive results in testing methods, leading to improper controls, are the major challenges on managing these diseases. In this study, we develop novel mathematical models describing the co-infection dynamics of malaria and typhoid. Through mathematical analyses of our models, we identify distinct features of typhoid and malaria infection dynamics as well as relationships associated to their co-infection. The global dynamics of typhoid can be determined by a single threshold (the typhoid basic reproduction number, R0(T)) while two thresholds (the malaria basic reproduction number, R0(M), and the extinction index, R0(MM)) are needed to determine the global dynamics of malaria. We demonstrate that by using efficient simultaneous prevention programs, the co-infection basic reproduction number, R0, can be brought down to below one, thereby eradicating the diseases. Using our model, we present illustrative numerical results with a case study in the Eastern Province of Kenya to quantify the possible false diagnosis resulting from this co-infection. In Kenya, despite having higher prevalence of typhoid, malaria is more problematic in terms of new infections and disease deaths. We find that false diagnosis-with higher possible cases for typhoid than malaria-cause significant devastating impacts on Kenyan societies. Our results demonstrate that both diseases need to be simultaneously managed for successful control of co-epidemics. Copyright © 2015 Elsevier Inc. All rights reserved.

Passive radiofrequency shimming in the thighs at 3 Tesla using high permittivity materials and body coil receive uniformity correction.

PubMed

Brink, Wyger M; Versluis, Maarten J; Peeters, Johannes M; Börnert, Peter; Webb, Andrew G

2016-12-01

To explore the effects of high permittivity dielectric pads on the transmit and receive characteristics of a 3 Tesla body coil centered at the thighs, and their implications on image uniformity in receive array applications. Transmit and receive profiles of the body coil with and without dielectric pads were simulated and measured in healthy volunteers. Parallel imaging was performed using sensitivity encoding (SENSE) with and without pads. An intensity correction filter was constructed from the measured receive profile of the body coil. Measured and simulated data show that the dielectric pads improve the transmit homogeneity of the body coil in the thighs, but decrease its receive homogeneity, which propagates into reconstruction algorithms in which the body coil is used as a reference. However, by correcting for the body coil reception profile this effect can be mitigated. Combining high permittivity dielectric pads with an appropriate body coil receive sensitivity filter improves the image uniformity substantially compared with the situation without pads. Magn Reson Med 76:1951-1956, 2016. © 2015 International Society for Magnetic Resonance in Medicine. © 2015 International Society for Magnetic Resonance in Medicine.

Chronic prostatic infection and inflammation by Propionibacterium acnes in a rat prostate infection model.

PubMed

Olsson, Jan; Drott, Johanna Bergh; Laurantzon, Lovisa; Laurantzon, Oscar; Bergh, Anders; Elgh, Fredrik

2012-01-01

Chronic inflammation in the prostate, seen as infiltration of inflammatory cells into the prostate gland in histological samples, affects approximately half the male population without indication of prostate disease, and is almost ubiquitous in patients diagnosed with benign prostate hyperplasia and cancer. Several studies have demonstrated the gram-positive bacterium Propionibacterium acnes to be frequently present in prostate tissue from men suffering from prostate disease. P. acnes has been shown to be associated with histological inflammation in human prostatectomy specimens, and also to induce strong inflammatory response in prostate-derived tissue culture models. The present paper describes a rat model for assessment of the pathogenic potential of P. acnes in prostate. Prostate glands of Sprague Dawley rats (n = 98) were exposed via an abdominal incision and live P. acnes or, in control rats, saline were injected into the ventral and dorso-lateral lobes. Rats were sacrificed 5 days, 3 weeks, 3 months and 6 months post infection, and prostate tissue was analyzed for bacterial content and histological inflammation. Rat sera were assessed for levels of CRP and anti-P. acnes IgG. Live P. acnes could be recovered from the dorso-lateral lobes up to 3 months post infection, while the ventral lobes were cleared from bacteria at that time. In samples up to 3 months post infection, the dorso-lateral lobes exhibited intense focal inflammation. CRP and IgG levels were elevated throughout the span of the experiment, and reached maximum levels 3 weeks and 3 months post infection, respectively. We show that P. acnes have the potential to cause chronic infection in previously healthy prostate, and that the infection has potential to cause chronic histological inflammation in the infected tissue. The high prevalence of P. acnes in human prostate tissue calls for resolution of pathogenic details. The present rat model suggests that complications such as chronic

Chronic Prostatic Infection and Inflammation by Propionibacterium acnes in a Rat Prostate Infection Model

PubMed Central

Olsson, Jan; Drott, Johanna Bergh; Laurantzon, Lovisa; Laurantzon, Oscar; Bergh, Anders; Elgh, Fredrik

2012-01-01

Chronic inflammation in the prostate, seen as infiltration of inflammatory cells into the prostate gland in histological samples, affects approximately half the male population without indication of prostate disease, and is almost ubiquitous in patients diagnosed with benign prostate hyperplasia and cancer. Several studies have demonstrated the Gram-positive bacterium Propionibacterium acnes to be frequently present in prostate tissue from men suffering from prostate disease. P. acnes has been shown to be associated with histological inflammation in human prostatectomy specimens, and also to induce strong inflammatory response in prostate-derived tissue culture models. The present paper describes a rat model for assessment of the pathogenic potential of P. acnes in prostate. Prostate glands of Sprague Dawley rats (n = 98) were exposed via an abdominal incision and live P. acnes or, in control rats, saline were injected into the ventral and dorso-lateral lobes. Rats were sacrificed 5 days, 3 weeks, 3 months and 6 months post infection, and prostate tissue was analyzed for bacterial content and histological inflammation. Rat sera were assessed for levels of CRP and anti-P. acnes IgG. Live P. acnes could be recovered from the dorso-lateral lobes up to 3 months post infection, while the ventral lobes were cleared from bacteria at that time. In samples up to 3 months post infection, the dorso-lateral lobes exhibited intense focal inflammation. CRP and IgG levels were elevated throughout the span of the experiment, and reached maximum levels 3 weeks and 3 months post infection, respectively. We show that P. acnes have the potential to cause chronic infection in previously healthy prostate, and that the infection has potential to cause chronic histological inflammation in the infected tissue. The high prevalence of P. acnes in human prostate tissue calls for resolution of pathogenic details. The present rat model suggests that complications such as chronic

Discrepancies between Skinned Single Muscle Fibres and Whole Thigh Muscle Function Characteristics in Young and Elderly Human Subjects

PubMed Central

2016-01-01

We aimed to analyse the mechanical properties of skinned single muscle fibres derived from the vastus lateralis (VL) muscle in relation to those of the whole intact thigh muscle and to compare any difference between young and older adults. Sixteen young men (29.25 ± 4.65 years), 11 older men (71.45 ± 2.94 years), 11 young women (29.64 ± 4.88 years), and 7 older women (67.29 ± 1.70 years) were recruited. In vivo analyses were performed for mechanical properties such as isokinetic performance, isometric torque, and power. Specific force and maximum shortening velocity (Vo) were measured with single muscle fibres. Sex difference showed greater impact on the functional properties of both the whole muscle (p < 0.01) and single muscle fibres than aging (p < 0.05). Sex difference, rather than aging, yielded more remarkable differences in gross mechanical properties in the single muscle fibre study in which significant differences between young men and young women were found only in the cross-sectional area and Vo (p < 0.05). Age and sex differences reflect the mechanical properties of both single muscle fibres and whole thigh muscle, with the whole muscle yielding more prominent functional properties. PMID:28070513

Experimental Models of Ocular Infection with Toxoplasma Gondii

PubMed Central

Dukaczewska, Agata; Tedesco, Roberto; Liesenfeld, Oliver

2015-01-01

Ocular toxoplasmosis is a vision-threatening disease and the major cause of posterior uveitis worldwide. In spite of the continuing global burden of ocular toxoplasmosis, many critical aspects of disease including the therapeutic approach to ocular toxoplasmosis are still under debate. To assist in addressing many aspects of the disease, numerous experimental models of ocular toxoplasmosis have been established. In this article, we present an overview on in vitro, ex vivo, and in vivo models of ocular toxoplasmosis available to date. Experimental studies on ocular toxoplasmosis have recently focused on mice. However, the majority of murine models established so far are based on intraperitoneal and intraocular infection with Toxoplasma gondii. We therefore also present results obtained in an in vivo model using peroral infection of C57BL/6 and NMRI mice that reflects the natural route of infection and mimics the disease course in humans. While advances have been made in ex vivo model systems or larger animals to investigate specific aspects of ocular toxoplasmosis, laboratory mice continue to be the experimental model of choice for the investigation of ocular toxoplasmosis. PMID:26716018

Establishment of a Neonatal Rhesus Macaque Model to Study Mycobacterium tuberculosis Infection

PubMed Central

Cepeda, Magdalena; Salas, Mary; Folwarczny, Jessica; Leandro, Ana C.; Hodara, Vida L.; de la Garza, Melissa A.; Dick, Edward J.; Owston, Michael; Armitige, Lisa Y.; Gauduin, Marie-Claire

2014-01-01

Summary Mycobacterium tuberculosis (Mtb) is the causative agent of human tuberculosis (TB) with an estimated 8.8 million new TB cases and 1.4 million deaths annually. Tuberculosis is the leading cause of death in AIDS patients worldwide but very little is known about early TB infection or TB/HIV co-infection in infants. A clinically relevant newborn animal model to study TB infection is urgently needed. We have successfully established an aerosol newborn/infant model in neonatal nonhuman primates (NHPs) that mimics clinical and bacteriological characteristics of Mtb infection as seen in human newborns/infants. Further, this model will allow the establishment of a TB coinfection model of pediatric AIDS. Aerosol versus intra broncho-alveolar Mtb infection was studied. Interestingly, 42 days post infection specific lesions were detected suggestive of the classic Ghon focus in human children. Concurrently, specific cellular immune responses developed 4–6 weeks after Mtb infection. Using the enzyme-linked immunospot (ELISPOT) assays, we found that IL-12 production correlated with early Mtb infection lesions seen by routine thoracic radiographs. Overall, this work represents the first example of early Mtb infection of newborn macaques. This study gives us a unique opportunity to further characterize immunopathogenesis and establish a TB/SIV co-infection model for pediatric AIDS. PMID:24388650

Wearing Compression Tights on the Thigh during Prolonged Running Attenuated Exercise-Induced Increase in Muscle Damage Marker in Blood

PubMed Central

Mizuno, Sahiro; Arai, Mari; Todoko, Fumihiko; Yamada, Eri; Goto, Kazushige

2017-01-01

Purpose: To examine the effects of wearing a lower-body compression garment with different body coverage areas during prolonged running on exercise performance and muscle damage. Methods: Thirty male subjects were randomly assigned to one of three groups: (1) wearing a compression tights with 15 mmHg to thigh [n = 10, CT group], (2) wearing a compression socks with 15 mmHg to calf [n = 10, CS group], and (3) wearing a lower-body garment with < 5 mmHg to thigh and calf [n = 10, CON group]. The exercise consisted of 120 min of uphill running at 55% of V˙O2max. Heart rate (HR), rate of perceived exertion (RPE), and running economy (evaluated by VO2) were monitored during exercise every 10 min. Changes in maximum voluntary contraction (MVC) of knee extension and plantar flexion, height of counter movement jump (CMJ) and drop jump (DJ), and scores of subjective feelings of muscle soreness and fatigue were evaluated before exercise, and 60 and 180 min after exercise. Blood samples were collected to determine blood glucose, lactate, serum free fatty acid, myoglobin (Mb), high-sensitivity C-reactive protein, and plasma interleukin-6 concentrations before exercise (after 20 min of rest), at 60 min of exercise, immediately after exercise, and 60 and 180 min after exercise. Results: Changes in HR, RPE, and running economy during exercise did not differ significantly among the three groups. MVC of knee extension and plantar flexion, and DJ decreased significantly following exercise, with no difference among groups. The serum Mb concentration increased significantly with exercise in all groups, whereas the area under the curve for Mb concentration during 180 min post-exercise was significantly lower in the CT group (13,833 ± 1,397 pg/mL 180 min) than in the CON group (24,343 ± 3,370 pg/mL 180 min, P = 0.03). Conclusion: Wearing compression garment on the thigh significantly attenuated the increase in serum Mb concentration after exercise, suggesting that exercise

Complex Intraoral Reconstruction Using a Single Free Anterolateral Thigh Flap and Supermicrosurgery After Corrosive Ingestion in a 14-Month-Old Child.

PubMed

El Fahar, Mohammed H

2018-05-01

Oral chemical burn injuries induce more damage to the underlying tissues with extensive scarring. It is very well known that alkali causes severe liquefaction necrosis and injury to the deeper tissues. Pediatric facial burns must be managed thoroughly and always require complex reconstruction, which is a challenging process. So, any reconstructive surgeon must be aware of all the deformities that may have significant functional and aesthetic impact on the burn survivors especially children. Few medical studies addressed pediatric microsurgical reconstruction for oral burn injuries induced by chemical materials. Anterolateral thigh (ALT) free flap is a common flap with a multitude of indications. The purpose of this article is to present the youngest case in the medical literature of caustic intraoral scarring managed with a very thin free anterolateral thigh flap in a 14-month-old child who underwent reconstruction of his inner cheek, the angle of the mouth and tongue using supermicrosurgery techniques. Further development of the surgical techniques is required to establish early and safe intraoral pediatric microsurgery with a long-term follow-up.

Intracellular hepatitis C modeling predicts infection dynamics and viral protein mechanisms

DOE PAGES

Aunins, Thomas R.; Marsh, Katherine M.; Subramanya, Gitanjali; ...

2018-03-21

Hepatitis C virus infection is a global health problem, with nearly 2 million new infections occurring every year and up to 85% of these becoming chronic infections that pose serious long-term health risks. To effectively reduce the prevalence of HCV infection and associated diseases, it is important to understand the intracellular dynamics of the viral lifecycle. Here, we present a detailed mathematical model that represents the full hepatitis C lifecycle. It is the first full HCV model to be fit to acute intracellular infection data and the first to explore the functions of distinct viral proteins, probing multiple hypotheses ofmore » cis- and trans-acting mechanisms to provide insights for drug targeting. Model parameters were derived from the literature, experiments, and fitting to experimental intracellular viral RNA, extracellular viral titer, and HCV core and NS3 protein kinetic data from viral inoculation to steady-state. Our model predicts faster rates for protein translation and polyprotein cleavage than previous replicon models and demonstrates that the processes of translation and synthesis of viral RNA have the most influence on the levels of the species we tracked in experiments. Overall, our experimental data and the resulting mathematical infection model reveal information about the regulation of core protein during infection, produce specific insights into the roles of the viral core, NS5A, and NS5B proteins, and demonstrate the sensitivities of viral proteins and RNA to distinct reactions within the lifecycle.« less

Intracellular hepatitis C modeling predicts infection dynamics and viral protein mechanisms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aunins, Thomas R.; Marsh, Katherine M.; Subramanya, Gitanjali

Hepatitis C virus infection is a global health problem, with nearly 2 million new infections occurring every year and up to 85% of these becoming chronic infections that pose serious long-term health risks. To effectively reduce the prevalence of HCV infection and associated diseases, it is important to understand the intracellular dynamics of the viral lifecycle. Here, we present a detailed mathematical model that represents the full hepatitis C lifecycle. It is the first full HCV model to be fit to acute intracellular infection data and the first to explore the functions of distinct viral proteins, probing multiple hypotheses ofmore » cis- and trans-acting mechanisms to provide insights for drug targeting. Model parameters were derived from the literature, experiments, and fitting to experimental intracellular viral RNA, extracellular viral titer, and HCV core and NS3 protein kinetic data from viral inoculation to steady-state. Our model predicts faster rates for protein translation and polyprotein cleavage than previous replicon models and demonstrates that the processes of translation and synthesis of viral RNA have the most influence on the levels of the species we tracked in experiments. Overall, our experimental data and the resulting mathematical infection model reveal information about the regulation of core protein during infection, produce specific insights into the roles of the viral core, NS5A, and NS5B proteins, and demonstrate the sensitivities of viral proteins and RNA to distinct reactions within the lifecycle.« less

Measures of Functional Performance and Their Association With Hip and Thigh Strength

PubMed Central

Kollock, Roger; Van Lunen, Bonnie L.; Ringleb, Stacie I.; Oñate, James A.

2015-01-01

Context: Insufficient hip and thigh strength may increase an athlete's susceptibility to injury. However, screening for strength deficits using isometric and isokinetic instrumentation may not be practical in all clinical scenarios. Objective: To determine if functional performance tests are valid indicators of hip and thigh strength. Design: Descriptive laboratory study. Setting: Research laboratory. Patients or Other Participants: Sixty-two recreationally athletic men (n = 30, age = 21.07 years, height = 173.84 cm, mass = 81.47 kg) and women (n = 32, age = 21.03 years, height = 168.77 cm, mass = 68.22 kg) participants were recruited. Intervention(s): During session 1, we measured isometric peak force and rate of force development for 8 lower extremity muscle groups, followed by an isometric endurance test. During session 2, participants performed functional performance tests. Main Outcome Measure(s): Peak force, rate of force development, fatigue index, hop distance (or height), work (joules), and number of hops performed during the 30-second lateral-hop test were assessed. The r values were squared to calculate r 2. We used Pearson correlations to evaluate the associations between functional performance and strength. Results: In men, the strongest relationship was observed between triple-hop work and hip-adductor peak force (r2 = 50, P ≤ .001). Triple-hop work also was related to hip-adductor (r2 = 38, P ≤ .01) and hip-flexor (r2 = 37, P ≤ .01) rate of force development. For women, the strongest relationships were between single-legged vertical-jump work and knee-flexor peak force (r2 = 0.44, P ≤ .01) and single-legged vertical-jump height and knee-flexor peak force (r2 = 0.42, P ≤ .01). Single-legged vertical-jump height also was related to knee-flexor rate of force development (r2 = 0.49, P ≤ .001). The 30-second lateral-hop test did not account for a significant portion of the variance in strength endurance. Conclusions: Hop tests alone did not

Murine neonatal infection provides an efficient model for congenital ocular toxoplasmosis.

PubMed

Lahmar, Ibtissem; Guinard, Marie; Sauer, Arnaud; Marcellin, Luc; Abdelrahman, Tamer; Roux, Michel; Mousli, Marc; Moussa, Adnan; Babba, Hamouda; Pfaff, Alexander W; Candolfi, Ermanno

2010-02-01

Congenital infection is one of the most serious settings of infection with the apicomplexan parasite Toxoplasma gondii. Ocular diseases, such as retinochoroiditis, are the most common sequels of such infection in utero. However, while numerous studies have investigated the physiopathology of acquired toxoplasmosis, congenital infection has been largely neglected so far. Here, we establish a mouse model of congenital ocular toxoplasmosis. Parasite load and ocular pathology have been followed for the first 4 weeks of life. Ocular infection developed slowly compared to cerebral infection. Even after 4 weeks, not all eyes were infected and ocular parasite load was low. Therefore, we evaluated a scheme of neonatal infection to overcome problems associated with congenital infection. Development of infection and physiopathology was similar, but at a higher, more reliable rate. In summary, we have established a valuable model of neonatal ocular toxoplasmosis, which facilitates the research of the underlying physiopathological mechanisms and new diagnostic approaches of this pathology. Copyright 2009 Elsevier Inc. All rights reserved.

A guinea pig model of Zika virus infection.

PubMed

Kumar, Mukesh; Krause, Keeton K; Azouz, Francine; Nakano, Eileen; Nerurkar, Vivek R

2017-04-11

Animal models are critical to understand disease and to develop countermeasures for the ongoing epidemic of Zika virus (ZIKV). Here we report that immunocompetent guinea pigs are susceptible to infection by a contemporary American strain of ZIKV. Dunkin-Hartley guinea pigs were inoculated with 10 6 plaque-forming units of ZIKV via subcutaneous route and clinical signs were observed. Viremia, viral load in the tissues, anti-ZIKV neutralizing antibody titer, and protein levels of multiple cytokine and chemokines were analyzed using qRT-PCR, plaque assay, plaque reduction neutralization test (PRNT) and multiplex immunoassay. Upon subcutaneous inoculation with PRVABC59 strain of ZIKV, guinea pigs demonstrated clinical signs of infection characterized by fever, lethargy, hunched back, ruffled fur, and decrease in mobility. ZIKV was detected in the whole blood and serum using qRT-PCR and plaque assay. Anti-ZIKV neutralizing antibody was detected in the infected animals using PRNT. ZIKV infection resulted in a dramatic increase in protein levels of multiple cytokines, chemokines and growth factors in the serum. ZIKV replication was observed in spleen and brain, with the highest viral load in the brain. This data demonstrate that after subcutaneous inoculation, the contemporary ZIKV strain is neurotropic in guinea pigs. The guinea pig model described here recapitulates various clinical features and viral kinetics observed in ZIKV-infected patients, and therefore may serve as a model to study ZIKV pathogenesis, including pregnancy outcomes and for evaluation of vaccines and therapeutics.

Embryonated chicken eggs: An experimental model for Pythium insidiosum infection.

PubMed

Verdi, Camila M; Jesus, Francielli P K; Kommers, Glaucia; Ledur, Pauline C; Azevedo, Maria I; Loreto, Erico S; Tondolo, Juliana S M; Andrade, Eduardo N C; Schlemmer, Karine B; Alves, Sydney H; Santurio, Janio M

2018-02-01

Pythiosis is a severe disease caused by Pythium insidiosum. Currently, the research on the treatment of pythiosis uses rabbits as an experimental infection model. To reduce the use of animals in scientific experimentation, alternative models are increasingly necessary options. The objective of this study was to establish a new experimental infection model for pythiosis using embryonated chicken eggs. First, we tested the inoculation of 4 zoospore concentrations into the egg allantoic cavity at 3 embryonic days. We observed that increased zoospore concentration causes a decrease in survival time, and at a later embryonic day (the 14th) of infection, embryos showed delayed mortality. To confirm the reproducibility of the model, we chose the 14th embryonic day for the inoculation of 50 zoospores/egg, and the experiment was repeated twice. Mortality began with 30% embryos 48 hours after inoculation, and 95% embryos died within 72 hours. There was no mortality in the uninfected control group. The infection was confirmed by culture, PCR and histopathology. Immunohistochemistry confirmed the presence of hyphae in blood vessels in the umbilical cords in 95% of embryos and only 1 liver (5%). Our results suggest that embryonated eggs can be a very useful alternative infection model to study pythiosis. © 2017 Blackwell Verlag GmbH.

Anterolateral thigh flap harvested from paralytic lower extremity in a patient with late polio sequel.

PubMed

Valentini, Valentino; Terenzi, Valentina; Cassoni, Andrea; Battisti, Andrea; Della Monaca, Marco; Malavasi, Roberto

2012-01-01

Free flap reconstruction is the treatment of choice after extensive head and neck tumour resection. When treating a patient with a previous disability, such as lower extremity paralysis secondary to poliomyelitis, it is important to offer the best reconstruction whilst preserving healthy extremities. We report the case of a 51-year-old man with a squamous cell carcinoma (SCC) of the right tongue and a left lower extremity paralysis secondary to an acute poliomyelitis during childhood in which reconstruction was successfully achieved with a left anterolateral thigh (ALT) free flap. Copyright © 2011 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Trichuris muris: a model of gastrointestinal parasite infection.

PubMed

Klementowicz, Joanna E; Travis, Mark A; Grencis, Richard K

2012-11-01

Infection with soil-transmitted gastrointestinal parasites, such as Trichuris trichiura, affects more than a billion people worldwide, causing significant morbidity and health problems especially in poverty-stricken developing countries. Despite extensive research, the role of the immune system in triggering parasite expulsion is incompletely understood which hinders the development of anti-parasite therapies. Trichuris muris infection in mice serves as a useful model of T. trichiura infection in humans and has proven to be an invaluable tool in increasing our understanding of the role of the immune system in promoting either susceptibility or resistance to infection. The old paradigm of a susceptibility-associated Th1 versus a resistance-associated Th2-type response has been supplemented in recent years with cell populations such as novel innate lymphoid cells, basophils, dendritic cells and regulatory T cells proposed to play an active role in responses to T. muris infection. Moreover, new immune-controlled mechanisms of expulsion, such as increased epithelial cell turnover and mucin secretion, have been described in recent years increasing the number of possible targets for anti-parasite therapies. In this review, we give a comprehensive overview of experimental work conducted on the T. muris infection model, focusing on important findings and the most recent reports on the role of the immune system in parasite expulsion.

Anthropometric Differences between HIV-Infected Individuals Prior to Antiretroviral Treatment and the General Population from 1998–2007: The AIDS Clinical Trials Group Longitudinal Linked Randomized Trials (ALLRT) Cohort and NHANES

PubMed Central

Atkinson, Benjamin E.; Krishnan, Supriya; Cox, Gary; Hulgan, Todd; Collier, Ann C.

2013-01-01

Objective To assess differences in body circumferences and body mass index (BMI, kg/m2) between antiretroviral treatment (ART) naïve HIV-infected and HIV-uninfected persons. Methods Waist, arm, and thigh circumferences and BMI were measured within the ALLRT and NHANES cohorts between 1998 and 2007. ALLRT is a prospective, longitudinal study of U.S. participants enrolled in randomized HIV treatment studies conducted by the AIDS Clinical Trials Group (ACTG). NHANES is a representative group of the US population. The cohorts were analyzed in two time periods, to account for trends towards increased adiposity. Anthropometrics were displayed in percentiles by age and sex. Multiple linear regression models examined differences between cohorts. Results ALLRT had more males (82% versus 48%, p<0.0001), more black participants (32% versus 23%, p<0.0001), and less Hispanics (21% versus 30%, p<0.0001) than NHANES. Mean BMI was smaller in ALLRT males and females compared to NHANES by 1.6–2.4 kg/m2 (p<0.0001). Mean waist and arm circumferences in both sexes and time periods were significantly smaller in ALLRT than in NHANES (p<0.0001). Mean thigh circumference in ALLRT was also smaller than NHANES among males (p<0.0001 in both time periods) and females (p = 0.01 in the early time period). Conclusions Differences in anthropometrics existed prior to ART initiation, in this large national cohort of HIV-infected individuals, compared to a representative HIV-uninfected cohort, indicating that HIV and its complications have important effects on body shape. Further longitudinal examination of anthropometrics in this HIV-infected cohort may provide additional insight into disease risk. Trial Registration NCT00001137 at www.clinicaltrials.gov. PMID:23755215

Cardiac and Vascular Responses to Thigh Cuffs and Respiratory Maneuvers on Crewmembers of the International Space Station

NASA Technical Reports Server (NTRS)

Hamilton, Douglas; Sargsyan, Ashot E.; Garcia, Kathleen; Ebert, Douglas; Whitson, Peggy A.; Feiveson, Alan; Alferova, Irina V.; Dulchavsky, Scott A.; Matveev, Vladimir P.; Bogomolov, Valery V.;

The susceptible-infected-recovered (SIR) model for viral marketing

NASA Astrophysics Data System (ADS)

Ismail, Siti Suhaila; Akil, Ku Azlina Ku; Chulan, Majdah; Sharif, Noorzila

2017-11-01

Viral marketing is a marketing strategy utilizes social media to spread information about a product or services provided. It is the most powerful way to share information in a short amount of time. The objective of this study is to investigate the dynamic of viral marketing within a time duration in the point of view of mathematics. This study used the epidemiological model known as Susceptible-Infected-Recovered (SIR). The model consists of a system of three differential equations with three state variables namely susceptible (S), infected (I) and recovered (R). It considers a case of SIR model with demography. Numerical experiments have been performed. The results show that viral marketing reaches its peak within two days. The online messages shared will become higher if the initial number of the infected individual has been increased.

In Vitro and In Vivo Synergy of the Oxadiazole Class of Antibacterials with β-Lactams.

PubMed

Janardhanan, Jeshina; Meisel, Jayda E; Ding, Derong; Schroeder, Valerie A; Wolter, William R; Mobashery, Shahriar; Chang, Mayland

2016-09-01

The oxadiazole antibacterials target the bacterial cell wall and are bactericidal. We investigated the synergism of ND-421 with the commonly used β-lactams and non-β-lactam antibiotics by the checkerboard method and by time-kill assays. ND-421 synergizes well with β-lactam antibiotics, and it also exhibits a long postantibiotic effect (4.7 h). We also evaluated the in vivo efficacy of ND-421 in a murine neutropenic thigh infection model alone and in combination with oxacillin. ND-421 has in vivo efficacy by itself in a clinically relevant infection model (1.49 log10 bacterial reduction for ND-321 versus 0.36 log10 for linezolid with NRS119) and acts synergistically with β-lactam antibiotics in vitro and in vivo, and the combination of ND-421 with oxacillin is efficacious in a mouse neutropenic thigh methicillin-resistant Staphylococcus aureus (MRSA) infection model (1.60 log10 bacterial reduction). The activity of oxacillin was potentiated in the presence of ND-421, as the strain would have been resistant to oxacillin otherwise. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

The relationship between maternal body composition in early pregnancy and foetal mid-thigh soft-tissue thickness in the third trimester in a high-risk obstetric population.

PubMed

Anglim, Breffini; Farah, Nadine; O'Connor, Clare; Daly, Niamh; Kennelly, Mairead M; Turner, Michael J

2017-07-01

Maternal obesity is an emerging challenge in contemporary obstetrics. To date there has been no study analysing the relationship between specific maternal body composition measurements and foetal soft-tissue measurements. The aim of this study was to determine whether measurement of maternal body composition at booking predicts foetal soft-tissue trajectories in the third trimester. We analysed the relationship between foetal thigh in the third trimester and both maternal BMI and body composition using the Tanita digital scales in the first trimester. Foetal subcutaneous thigh tissue measurements were obtained at intervals of 28, 32 and 36 weeks of gestation. A total of 160 women were identified. There was a direct correlation between MTST at 36 weeks and BMI (p = .002). There was a positive correlation between MTST at 36 weeks and leg fat mass (p = .13) and leg fat free mass (p = .013). There was a positive correlation between arm fat free mass and MTST at 36 weeks. We showed there is an association between maternal fat distribution and foetal subcutaneous thigh tissue measurements. MTST may be more useful in determining if a child is at risk of macrosomia. Impact statement Previous studies have suggested that maternal obesity programmes intrauterine foetal adiposity and growth. The aim of this study was to examine the relationship in a high-risk obstetric population between measurements of maternal body composition in early pregnancy and the assessment of foetal adiposity in the third trimester using serial ultrasound measurements of mid-thigh soft-tissue thickness. BMI is only a surrogate measurement of fat and does not measure fat distribution. Our study shows the distribution of both maternal fat and fat-free mass in early pregnancy may be positively associated with foetal soft-tissue measurements in the third trimester. Maternal arthropometric measurements other than BMI may help predict babies at risk of macrosomia and neonatal adiposity.

Numerical Investigations of Interactions between the Knee-Thigh-Hip Complex with Vehicle Interior Structures.

PubMed

Kim, Yong Sun; Choi, Hyeong Ho; Cho, Young Nam; Park, Yong Jae; Lee, Jong B; Yang, King H; King, Albert I

2005-11-01

Although biomechanical studies on the knee-thigh-hip (KTH) complex have been extensive, interactions between the KTH and various vehicular interior design parameters in frontal automotive crashes for newer models have not been reported in the open literature to the best of our knowledge. A 3D finite element (FE) model of a 50(th) percentile male KTH complex, which includes explicit representations of the iliac wing, acetabulum, pubic rami, sacrum, articular cartilage, femoral head, femoral neck, femoral condyles, patella, and patella tendon, has been developed to simulate injuries such as fracture of the patella, femoral neck, acetabulum, and pubic rami of the KTH complex. Model results compared favorably against regional component test data including a three-point bending test of the femur, axial loading of the isolated knee-patella, axial loading of the KTH complex, axial loading of the femoral head, and lateral loading of the isolated pelvis. The model was further integrated into a Wayne State University upper torso model and validated against data obtained from whole body sled tests. The model was validated against these experimental data over a range of impact speeds, impactor masses and boundary conditions. Using Design Of Experiment (DOE) methods based on Taguchi's approach and the developed FE model of the whole body, including the KTH complex, eight vehicular interior design parameters, namely the load limiter force, seat belt elongation, pretensioner inlet amount, knee-knee bolster distance, knee bolster angle, knee bolster stiffness, toe board angle and impact speed, each with either two or three design levels, were simulated to predict their respective effects on the potential of KTH injury in frontal impacts. Simulation results proposed best design levels for vehicular interior design parameters to reduce the injury potential of the KTH complex due to frontal automotive crashes. This study is limited by the fact that prediction of bony fracture was

Animal models for studying female genital tract infection with Chlamydia trachomatis.

PubMed

De Clercq, Evelien; Kalmar, Isabelle; Vanrompay, Daisy

2013-09-01

Chlamydia trachomatis is a Gram-negative obligate intracellular bacterial pathogen. It is the leading cause of bacterial sexually transmitted disease in the world, with more than 100 million new cases of genital tract infections with C. trachomatis occurring each year. Animal models are indispensable for the study of C. trachomatis infections and the development and evaluation of candidate vaccines. In this paper, the most commonly used animal models to study female genital tract infections with C. trachomatis will be reviewed, namely, the mouse, guinea pig, and nonhuman primate models. Additionally, we will focus on the more recently developed pig model.

An experimental infection model to induce digital dermatitis infection in cattle.

PubMed

Gomez, A; Cook, N B; Bernardoni, N D; Rieman, J; Dusick, A F; Hartshorn, R; Socha, M T; Read, D H; Döpfer, D

2012-04-01

Bovine digital dermatitis (DD), also known as papillomatous digital dermatitis (foot warts), has been recognized as a major cause of lameness in cattle, with important economic and welfare consequences. The evaluation of therapeutic and preventive interventions aiming to control DD infections in dairy cattle is often challenged by the complex multifactorial etiology of the disease. An experimental infection model to induce acute DD lesions in a controlled environment is proposed. The goal was to provide a standard way of reproducing DD infections independent of external factors that could confound the natural course of the disease, such as management practices or infection pressure, resulting in transmission of DD between animals. A group of 4 yearling Holstein heifers free of any clinical evidence of hoof disease was recruited from a commercial dairy farm and housed in an experimental facility in 1 pen with slatted flooring. The hind feet were wrapped to mimic conditions of prolonged moisture (maceration) and reduced access to air (closure) and inoculated at the heel and dewclaw areas with a homogenate of a naturally occurring DD lesion skin biopsy or a culture broth of Treponema spp. After a period of 12 to 25 d, 4 of 6 and 1 of 4 dewclaw areas inoculated with biopsied DD lesion or a Treponema spp. culture, respectively, had gross lesions compatible with DD. Histopathology confirmed the gross diagnosis in the sites inoculated with tissue homogenate. In the site inoculated with Treponema spp. culture broth, histopathology revealed an incipient DD lesion. Treponema spp. were detected by PCR in both naturally occurring DD homogenate and Treponema spp. culture broth inoculation sites. An experimental infection model to induce acute DD in cattle was developed, which may be used to evaluate interventions to control DD and study the pathogenesis of this infectious hoof disease in a controlled manner. Copyright © 2012 American Dairy Science Association. Published by

THIGH MUSCLE CROSS-SECTIONAL AREAS AND STRENGTH IN KNEES WITH EARLY VS KNEES WITHOUT RADIOGRAPHIC KNEE OSTEOARTHRITIS: A BETWEEN-KNEE, WITHIN-PERSON COMPARISON

PubMed Central

Ruhdorfer, AS; Dannhauer, T; Wirth, W; Cotofana, S; Roemer, F; Nevitt, M; Eckstein, F

2014-01-01

Objective To compare cross-sectional and longitudinal side-differences in thigh muscle anatomical cross-sectional areas (ACSAs), muscle strength, and specific strength (strength/ACSA), between knees with early radiographic change vs. knees without radiographic knee osteoarthritis (RKOA), in the same person. Design 55 (of 4796) Osteoarthritis Initiative participants fulfilled the inclusion criteria of early RKOA in one limb (definite tibiofemoral osteophytes; no radiographic joint space narrowing [JSN]) vs. no RKOA (no osteophyte; no JSN) in the contralateral limb. ACSAs of the thigh muscles and quadriceps heads were determined using axial MRIs at 33%/30% femoral length (distal to proximal). Isometric extensor and flexor muscle strength were measured (Good Strength Chair). Baseline quadriceps ACSA and extensor (specific) strength represented the primary analytic focus, and two-year changes of quadriceps ACSAs the secondary focus. Results No statistically significant side-differences in quadriceps (or other thigh muscle) ACSAs, muscle strength, or specific strength were observed between early RKOA vs. contralateral limbs without RKOA (p≥0.44), neither in men nor in women. The two-year reduction in quadriceps ACSA in limbs with early RKOA was −0.9±6% (mean ± standard deviation) vs. −0.5±6% in limbs without RKOA (statistical difference p=0.85). Conclusion Our results do not provide evidence that early unilateral radiographic changes, i.e. presence of osteophytes, are associated with cross-sectional or longitudinal differences in quadriceps muscle status compared with contralateral knees without RKOA. At the stage of early unilateral RKOA there thus appears to be no clinical need for countervailing a potential dys-balance in quadriceps ACSAs and strength between both knees. PMID:25278072

Reconstruction of trochanteric pressure sores with pedicled anterolateral thigh myocutaneous flaps.

PubMed

Wang, Chih-Hsin; Chen, Shih-Yi; Fu, Ju-Peng; Dai, Niann-Tzyy; Chen, Shao-Liang; Chen, Tim-Mo; Chen, Shyi-Gen

2011-05-01

To provide an alternative choice for covering trochanteric pressure sores, we report on a modified pedicle anterolateral thigh (ALT) myocutaneous flap based on the descending branch of the lateral circumflex femoral artery. From August 2007 to January 2010, 20 consecutive patients (10 men and 10 women) underwent 21 pedicled ALT myocutaneous flaps for reconstruction of trochanteric pressure sores. The flap was designed and elevated, resembling the ALT perforator flap including part of the vastus lateralis muscle but without skeletonisation of the perforators. The mean age of patients was 79.4 years (range: 46-103). The mean follow-up period was 13.9 months (range: 3-32). The flaps were 8-21 cm long and 5-11 cm wide. All flaps healed without major complications. All donor sites were closed primarily without skin grafting and showed good aesthetic results. No recurrence was observed. This modified design of pedicled ALT myocutaneous flap without skeletonisation of perforators is a reliable and easily harvested flap for reconstruction of trochanteric pressure sores with limited morbidity. Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.

Multiscale model for pedestrian and infection dynamics during air travel

NASA Astrophysics Data System (ADS)

Namilae, Sirish; Derjany, Pierrot; Mubayi, Anuj; Scotch, Mathew; Srinivasan, Ashok

2017-05-01

In this paper we develop a multiscale model combining social-force-based pedestrian movement with a population level stochastic infection transmission dynamics framework. The model is then applied to study the infection transmission within airplanes and the transmission of the Ebola virus through casual contacts. Drastic limitations on air-travel during epidemics, such as during the 2014 Ebola outbreak in West Africa, carry considerable economic and human costs. We use the computational model to evaluate the effects of passenger movement within airplanes and air-travel policies on the geospatial spread of infectious diseases. We find that boarding policy by an airline is more critical for infection propagation compared to deplaning policy. Enplaning in two sections resulted in fewer infections than the currently followed strategy with multiple zones. In addition, we found that small commercial airplanes are better than larger ones at reducing the number of new infections in a flight. Aggregated results indicate that passenger movement strategies and airplane size predicted through these network models can have significant impact on an event like the 2014 Ebola epidemic. The methodology developed here is generic and can be readily modified to incorporate the impact from the outbreak of other directly transmitted infectious diseases.

Targeting Apoptosis for Optical Imaging of Infection

PubMed Central

Thakur, Mathew L.; Zhang, Kaijun; Paudyal, Bishnuhari; Devakumar, Devadhas; Covarrubias, Maria Y.; Cheng, Changpo; Gray, Brian D.; Wickstrom, Eric; Pak, Koon Y.

2018-01-01

Purpose Infection is ubiquitous and a major cause of morbidity and mortality. The most reliable method for localizing infection requires radiolabeling autologous white blood cells ex vivo. A compound that can be injected directly into a patient and can selectively image infectious foci will eliminate the drawbacks. The resolution of infection is associated with neutrophil apoptosis and necrosis presenting phosphatidylserine (PS) on the neutrophil outer leaflet. Targeting PS with intravenous administration of a PS-specific, near-infrared (NIR) fluorophore will permit localization of infectious foci by optical imaging. Methods Bacterial infection and sterile inflammation were induced in separate groups (n=5) of mice. PS was targeted with a NIR fluorophore, PSVue®794 (2.7 pmol). Imaging was performed (ex=730 nm, em=830 nm) using Kodak Multispectral FX-Pro system. The contralateral normal thigh served as an individualized control. Confocal microscopy of normal and apoptotic neutrophils and bacteria confirmed PS specificity. Results Lesions, with a 10-s image acquisition, were unequivocally visible at 5 min post-injection. At 3 h post-injection, the lesion to background intensity ratios in the foci of infection (6.6±0.2) were greater than those in inflammation (3.2±0.5). Image fusions confirmed anatomical locations of the lesions. Confocal microscopy determined the fluorophore specificity for PS. Conclusions Targeting PS presented on the outer leaflet of apoptotic or necrotic neutrophils as well as gram-positive microorganism with PS-specific NIR fluorophore provides a sensitive means of imaging infection. Literature indicates that NIR fluorophores can be detected 7-14 cm deep in tissue. This observation together with the excellent results and the continued development of versatile imaging devices could make optical imaging a simple, specific, and rapid modality for imaging infection. PMID:21538153

Chronic hepatitis B infection and HBV DNA-containing capsids: Modeling and analysis

NASA Astrophysics Data System (ADS)

Manna, Kalyan; Chakrabarty, Siddhartha P.

2015-05-01

We analyze the dynamics of chronic HBV infection taking into account both uninfected and infected hepatocytes along with the intracellular HBV DNA-containing capsids and the virions. While previous HBV models have included either the uninfected hepatocytes or the intracellular HBV DNA-containing capsids, our model accounts for both these two populations. We prove the conditions for local and global stability of both the uninfected and infected steady states in terms of the basic reproduction number. Further, we incorporate a time lag in the model to encompass the intracellular delay in the production of the infected hepatocytes and find that this delay does not affect the overall dynamics of the system. The results for the model and the delay model are finally numerically illustrated.

Clostridium Difficile Infection Due to Pneumonia Treatment: Mortality Risk Models.

PubMed

Chmielewska, M; Zycinska, K; Lenartowicz, B; Hadzik-Błaszczyk, M; Cieplak, M; Kur, Z; Wardyn, K A

2017-01-01

One of the most common gastrointestinal infection after the antibiotic treatment of community or nosocomial pneumonia is caused by the anaerobic spore Clostridium difficile (C. difficile). The aim of this study was to retrospectively assess mortality due to C. difficile infection (CDI) in patients treated for pneumonia. We identified 94 cases of post-pneumonia CDI out of the 217 patients with CDI. The mortality issue was addressed by creating a mortality risk models using logistic regression and multivariate fractional polynomial analysis. The patients' demographics, clinical features, and laboratory results were taken into consideration. To estimate the influence of the preceding respiratory infection, a pneumonia severity scale was included in the analysis. The analysis showed two statistically significant and clinically relevant mortality models. The model with the highest prognostic strength entailed age, leukocyte count, serum creatinine and urea concentration, hematocrit, coexisting neoplasia or chronic obstructive pulmonary disease. In conclusion, we report on two prognostic models, based on clinically relevant factors, which can be of help in predicting mortality risk in C. difficile infection, secondary to the antibiotic treatment of pneumonia. These models could be useful in preventive tailoring of individual therapy.

Epidemic threshold of the susceptible-infected-susceptible model on complex networks

NASA Astrophysics Data System (ADS)

Lee, Hyun Keun; Shim, Pyoung-Seop; Noh, Jae Dong

2013-06-01

We demonstrate that the susceptible-infected-susceptible (SIS) model on complex networks can have an inactive Griffiths phase characterized by a slow relaxation dynamics. It contrasts with the mean-field theoretical prediction that the SIS model on complex networks is active at any nonzero infection rate. The dynamic fluctuation of infected nodes, ignored in the mean field approach, is responsible for the inactive phase. It is proposed that the question whether the epidemic threshold of the SIS model on complex networks is zero or not can be resolved by the percolation threshold in a model where nodes are occupied in degree-descending order. Our arguments are supported by the numerical studies on scale-free network models.

Modeling dynamics of HIV infected cells using stochastic cellular automaton

NASA Astrophysics Data System (ADS)

Precharattana, Monamorn; Triampo, Wannapong

2014-08-01

Ever since HIV was first diagnosed in human, a great number of scientific works have been undertaken to explore the biological mechanisms involved in the infection and progression of the disease. Several cellular automata (CA) models have been introduced to gain insights into the dynamics of the disease progression but none of them has taken into account effects of certain immune cells such as the dendritic cells (DCs) and the CD8+ T lymphocytes (CD8+ T cells). In this work, we present a CA model, which incorporates effects of the HIV specific immune response focusing on the cell-mediated immunities, and investigate the interaction between the host immune response and the HIV infected cells in the lymph nodes. The aim of our work is to propose a model more realistic than the one in Precharattana et al. (2010) [10], by incorporating roles of the DCs, the CD4+ T cells, and the CD8+ T cells into the model so that it would reproduce the HIV infection dynamics during the primary phase of HIV infection.

Predicting the effects of muscle activation on knee, thigh, and hip injuries in frontal crashes using a finite-element model with muscle forces from subject testing and musculoskeletal modeling.

PubMed

Chang, Chia-Yuan; Rupp, Jonathan D; Reed, Matthew P; Hughes, Richard E; Schneider, Lawrence W

2009-11-01

In a previous study, the authors reported on the development of a finite-element model of the midsize male pelvis and lower extremities with lower-extremity musculature that was validated using PMHS knee-impact response data. Knee-impact simulations with this model were performed using forces from four muscles in the lower extremities associated with two-foot bracing reported in the literature to provide preliminary estimates of the effects of lower-extremity muscle activation on knee-thigh-hip injury potential in frontal impacts. The current study addresses a major limitation of these preliminary simulations by using the AnyBody three-dimensional musculoskeletal model to estimate muscle forces produced in 35 muscles in each lower extremity during emergency one-foot braking. To check the predictions of the AnyBody Model, activation levels of twelve major muscles in the hip and lower extremities were measured using surface EMG electrodes on 12 midsize-male subjects performing simulated maximum and 50% of maximum braking in a laboratory seating buck. Comparisons between test results and the predictions of the AnyBody Model when it was used to simulate these same braking tests suggest that the AnyBody model appropriately predicts agonistic muscle activations but under predicts antagonistic muscle activations. Simulations of knee-to-knee-bolster impacts were performed by impacting the knees of the lower-extremity finite element model with and without the muscle forces predicted by the validated AnyBody Model. Results of these simulations confirm previous findings that muscle tension increases knee-impact force by increasing the effective mass of the KTH complex due to tighter coupling of muscle mass to bone. They also indicate that muscle activation preferentially couples mass distal to the hip, thereby accentuating the decrease in femur force from the knee to the hip. However, the reduction in force transmitted from the knee to the hip is offset by the increased force

Optimal control of predator-prey mathematical model with infection and harvesting on prey

NASA Astrophysics Data System (ADS)

Diva Amalia, R. U.; Fatmawati; Windarto; Khusnul Arif, Didik

2018-03-01

This paper presents a predator-prey mathematical model with infection and harvesting on prey. The infection and harvesting only occur on the prey population and it assumed that the prey infection would not infect predator population. We analysed the mathematical model of predator-prey with infection and harvesting in prey. Optimal control, which is a prevention of the prey infection, also applied in the model and denoted as U. The purpose of the control is to increase the susceptible prey. The analytical result showed that the model has five equilibriums, namely the extinction equilibrium (E 0), the infection free and predator extinction equilibrium (E 1), the infection free equilibrium (E 2), the predator extinction equilibrium (E 3), and the coexistence equilibrium (E 4). The extinction equilibrium (E 0) is not stable. The infection free and predator extinction equilibrium (E 1), the infection free equilibrium (E 2), also the predator extinction equilibrium (E 3), are locally asymptotically stable with some certain conditions. The coexistence equilibrium (E 4) tends to be locally asymptotically stable. Afterwards, by using the Maximum Pontryagin Principle, we obtained the existence of optimal control U. From numerical simulation, we can conclude that the control could increase the population of susceptible prey and decrease the infected prey.

Modelling Wolbachia infection in a sex-structured mosquito population carrying West Nile virus.

PubMed

Farkas, József Z; Gourley, Stephen A; Liu, Rongsong; Yakubu, Abdul-Aziz

2017-09-01

Wolbachia is possibly the most studied reproductive parasite of arthropod species. It appears to be a promising candidate for biocontrol of some mosquito borne diseases. We begin by developing a sex-structured model for a Wolbachia infected mosquito population. Our model incorporates the key effects of Wolbachia infection including cytoplasmic incompatibility and male killing. We also allow the possibility of reduced reproductive output, incomplete maternal transmission, and different mortality rates for uninfected/infected male/female individuals. We study the existence and local stability of equilibria, including the biologically relevant and interesting boundary equilibria. For some biologically relevant parameter regimes there may be multiple coexistence steady states including, very importantly, a coexistence steady state in which Wolbachia infected individuals dominate. We also extend the model to incorporate West Nile virus (WNv) dynamics, using an SEI modelling approach. Recent evidence suggests that a particular strain of Wolbachia infection significantly reduces WNv replication in Aedes aegypti. We model this via increased time spent in the WNv-exposed compartment for Wolbachia infected female mosquitoes. A basic reproduction number [Formula: see text] is computed for the WNv infection. Our results suggest that, if the mosquito population consists mainly of Wolbachia infected individuals, WNv eradication is likely if WNv replication in Wolbachia infected individuals is sufficiently reduced.

New Methods in Tissue Engineering: Improved Models for Viral Infection.

PubMed

Ramanan, Vyas; Scull, Margaret A; Sheahan, Timothy P; Rice, Charles M; Bhatia, Sangeeta N

2014-11-01

New insights in the study of virus and host biology in the context of viral infection are made possible by the development of model systems that faithfully recapitulate the in vivo viral life cycle. Standard tissue culture models lack critical emergent properties driven by cellular organization and in vivo-like function, whereas animal models suffer from limited susceptibility to relevant human viruses and make it difficult to perform detailed molecular manipulation and analysis. Tissue engineering techniques may enable virologists to create infection models that combine the facile manipulation and readouts of tissue culture with the virus-relevant complexity of animal models. Here, we review the state of the art in tissue engineering and describe how tissue engineering techniques may alleviate some common shortcomings of existing models of viral infection, with a particular emphasis on hepatotropic viruses. We then discuss possible future applications of tissue engineering to virology, including current challenges and potential solutions.

A Murine Model for Escherichia coli Urinary Tract Infection.

PubMed

Hannan, Thomas J; Hunstad, David A

2016-01-01

Urinary tract infections (UTI) are among the most common bacterial infections of humans. The mouse provides an excellent and tractable model system for cystitis and pyelonephritis caused by Escherichia coli and other uropathogens. Using a well-established model of experimental cystitis in which the bladders of female mice are infected via transurethral catheterization, the molecular details of the pathogenesis of bacterial cystitis have been substantially illuminated in the last decade. Uropathogenic E. coli attach to bladder epithelium (both in human and mouse) via adhesive type 1 pili, establish a replicative niche within epithelial cell cytoplasm, and form intracellular bacterial communities that are protected from antibiotic effects and immune clearance. The use of different inbred and mutant mouse strains offers the opportunity to study outcomes of infection, including resolution, formation of quiescent intracellular bacterial reservoirs, chronic bacterial cystitis, and recurrent infections. Urine, bladder, and kidney tissues can be analyzed by bacterial culture, histology, immunohistochemistry, immunofluorescent and confocal microscopy, electron microscopy, and flow cytometry, while a broad array of soluble markers (e.g., cytokines) can also be profiled in serum, urine, and tissue homogenates by ELISA, Western blotting, multiplex bead array, and other approaches. This model promises to afford continued opportunity for discovery of pathogenic mechanisms and evaluation of therapeutic and preventive strategies for acute, chronic, and recurrent UTI.

A 71-Year-Old Female with Myocardial Infarction and Long-Standing Ulcers on the Thigh

PubMed Central

De Flammineis, Eduardo; Mulvaney, Patrick M.; Kraft, Stefan; Mihm Jr., Martin C.; Das, Shinjita; Kroshinsky, Daniela

2017-01-01

Calciphylaxis is most commonly encountered in patients with end-stage renal disease; however, it is increasingly observed in nonuremic patients as well. It is important to consider and diagnose nonuremic calciphylaxis early, as prompt treatment and mitigation of associated risk factors is essential to improve long-term outcomes for these patients. Here, we present the case of a 71-year-old woman with atrial fibrillation on warfarin, but without renal disease, who presented with two long-standing ulcers on her thigh and was diagnosed with the aid of biopsy with calciphylaxis. We review the existing literature on the subject and offer this case as a representative report of a clinicopathologic correlation for this disorder. PMID:29456997

ModeLang: a new approach for experts-friendly viral infections modeling.

PubMed

Wasik, Szymon; Prejzendanc, Tomasz; Blazewicz, Jacek

2013-01-01

Computational modeling is an important element of systems biology. One of its important applications is modeling complex, dynamical, and biological systems, including viral infections. This type of modeling usually requires close cooperation between biologists and mathematicians. However, such cooperation often faces communication problems because biologists do not have sufficient knowledge to understand mathematical description of the models, and mathematicians do not have sufficient knowledge to define and verify these models. In many areas of systems biology, this problem has already been solved; however, in some of these areas there are still certain problematic aspects. The goal of the presented research was to facilitate this cooperation by designing seminatural formal language for describing viral infection models that will be easy to understand for biologists and easy to use by mathematicians and computer scientists. The ModeLang language was designed in cooperation with biologists and its computer implementation was prepared. Tests proved that it can be successfully used to describe commonly used viral infection models and then to simulate and verify them. As a result, it can make cooperation between biologists and mathematicians modeling viral infections much easier, speeding up computational verification of formulated hypotheses.

ModeLang: A New Approach for Experts-Friendly Viral Infections Modeling

PubMed Central

Blazewicz, Jacek

2013-01-01

Computational modeling is an important element of systems biology. One of its important applications is modeling complex, dynamical, and biological systems, including viral infections. This type of modeling usually requires close cooperation between biologists and mathematicians. However, such cooperation often faces communication problems because biologists do not have sufficient knowledge to understand mathematical description of the models, and mathematicians do not have sufficient knowledge to define and verify these models. In many areas of systems biology, this problem has already been solved; however, in some of these areas there are still certain problematic aspects. The goal of the presented research was to facilitate this cooperation by designing seminatural formal language for describing viral infection models that will be easy to understand for biologists and easy to use by mathematicians and computer scientists. The ModeLang language was designed in cooperation with biologists and its computer implementation was prepared. Tests proved that it can be successfully used to describe commonly used viral infection models and then to simulate and verify them. As a result, it can make cooperation between biologists and mathematicians modeling viral infections much easier, speeding up computational verification of formulated hypotheses. PMID:24454531

Modelling the Course of an HIV Infection: Insights from Ecology and Evolution

PubMed Central

Alizon, Samuel; Magnus, Carsten

2012-01-01

The Human Immunodeficiency Virus (HIV) is one of the most threatening viral agents. This virus infects approximately 33 million people, many of whom are unaware of their status because, except for flu-like symptoms right at the beginning of the infection during the acute phase, the disease progresses more or less symptom-free for 5 to 10 years. During this asymptomatic phase, the virus slowly destroys the immune system until the onset of AIDS when opportunistic infections like pneumonia or Kaposi’s sarcoma can overcome immune defenses. Mathematical models have played a decisive role in estimating important parameters (e.g., virion clearance rate or life-span of infected cells). However, most models only account for the acute and asymptomatic latency phase and cannot explain the progression to AIDS. Models that account for the whole course of the infection rely on different hypotheses to explain the progression to AIDS. The aim of this study is to review these models, present their technical approaches and discuss the robustness of their biological hypotheses. Among the few models capturing all three phases of an HIV infection, we can distinguish between those that mainly rely on population dynamics and those that involve virus evolution. Overall, the modeling quest to capture the dynamics of an HIV infection has improved our understanding of the progression to AIDS but, more generally, it has also led to the insight that population dynamics and evolutionary processes can be necessary to explain the course of an infection. PMID:23202449

Robustness of a cellular automata model for the HIV infection

NASA Astrophysics Data System (ADS)

Figueirêdo, P. H.; Coutinho, S.; Zorzenon dos Santos, R. M.

2008-11-01

An investigation was conducted to study the robustness of the results obtained from the cellular automata model which describes the spread of the HIV infection within lymphoid tissues [R.M. Zorzenon dos Santos, S. Coutinho, Phys. Rev. Lett. 87 (2001) 168102]. The analysis focused on the dynamic behavior of the model when defined in lattices with different symmetries and dimensionalities. The results illustrated that the three-phase dynamics of the planar models suffered minor changes in relation to lattice symmetry variations and, while differences were observed regarding dimensionality changes, qualitative behavior was preserved. A further investigation was conducted into primary infection and sensitiveness of the latency period to variations of the model’s stochastic parameters over wide ranging values. The variables characterizing primary infection and the latency period exhibited power-law behavior when the stochastic parameters varied over a few orders of magnitude. The power-law exponents were approximately the same when lattice symmetry varied, but there was a significant variation when dimensionality changed from two to three. The dynamics of the three-dimensional model was also shown to be insensitive to variations of the deterministic parameters related to cell resistance to the infection, and the necessary time lag to mount the specific immune response to HIV variants. The robustness of the model demonstrated in this work reinforce that its basic hypothesis are consistent with the three-stage dynamic of the HIV infection observed in patients.

Quantifying Abdominal Adipose Tissue and Thigh Muscle Volume and Hepatic Proton Density Fat Fraction: Repeatability and Accuracy of an MR Imaging-based, Semiautomated Analysis Method.

PubMed

Middleton, Michael S; Haufe, William; Hooker, Jonathan; Borga, Magnus; Dahlqvist Leinhard, Olof; Romu, Thobias; Tunón, Patrik; Hamilton, Gavin; Wolfson, Tanya; Gamst, Anthony; Loomba, Rohit; Sirlin, Claude B

2017-05-01

Purpose To determine the repeatability and accuracy of a commercially available magnetic resonance (MR) imaging-based, semiautomated method to quantify abdominal adipose tissue and thigh muscle volume and hepatic proton density fat fraction (PDFF). Materials and Methods This prospective study was institutional review board- approved and HIPAA compliant. All subjects provided written informed consent. Inclusion criteria were age of 18 years or older and willingness to participate. The exclusion criterion was contraindication to MR imaging. Three-dimensional T1-weighted dual-echo body-coil images were acquired three times. Source images were reconstructed to generate water and calibrated fat images. Abdominal adipose tissue and thigh muscle were segmented, and their volumes were estimated by using a semiautomated method and, as a reference standard, a manual method. Hepatic PDFF was estimated by using a confounder-corrected chemical shift-encoded MR imaging method with hybrid complex-magnitude reconstruction and, as a reference standard, MR spectroscopy. Tissue volume and hepatic PDFF intra- and interexamination repeatability were assessed by using intraclass correlation and coefficient of variation analysis. Tissue volume and hepatic PDFF accuracy were assessed by means of linear regression with the respective reference standards. Results Adipose and thigh muscle tissue volumes of 20 subjects (18 women; age range, 25-76 years; body mass index range, 19.3-43.9 kg/m 2 ) were estimated by using the semiautomated method. Intra- and interexamination intraclass correlation coefficients were 0.996-0.998 and coefficients of variation were 1.5%-3.6%. For hepatic MR imaging PDFF, intra- and interexamination intraclass correlation coefficients were greater than or equal to 0.994 and coefficients of variation were less than or equal to 7.3%. In the regression analyses of manual versus semiautomated volume and spectroscopy versus MR imaging, PDFF slopes and intercepts were close

The Project Protect Infection Prevention Fellowship: A model for advancing infection prevention competency, quality improvement, and patient safety.

PubMed

Reisinger, Janine D; Wojcik, Anna; Jenkins, Ian; Edson, Barbara; Pegues, David A; Greene, Linda

2017-08-01

The Centers for Disease Control and Prevention 2016 Healthcare-Associated Infections (HAI) Progress Report documented no change in catheter-associated urinary tract infections (CAUTIs) between 2009 and 2014. There is a need for investment in additional efforts to reduce HAIs, specifically CAUTI. Quality improvement fellowships are 1 approach to expand the capacity of dedicated leaders and infection prevention champions. The fellowship used a model that expanded collaboration among disciplines and focused on partnership by recruiting a diverse cohort of fellows and by providing 1-on-1 mentoring to enhance leadership development. The curriculum supported the Association for Professionals in Infection Control and Prevention Competency Model in 2 domains: leadership and performance improvement and implementation science. The fellowship was successful. The fellows and mentors had self-reported high level of satisfaction, fellows' knowledge increased, and they demonstrated leadership, quality improvement, and implementation science competency within the completed capstone projects. A model encompassing diverse educational topics, discussions, workshops, and mentorship can serve as a template for developing infection prevention champions. Although this project focused on CAUTI, this template can be used in a variety of settings and applied to a range of other HAIs and performance improvement projects. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. All rights reserved.

Long-term follow-up of MRI changes in thigh muscles of patients with Facioscapulohumeral dystrophy: A quantitative study.

PubMed

Fatehi, Farzad; Salort-Campana, Emmanuelle; Le Troter, Arnaud; Lareau-Trudel, Emilie; Bydder, Mark; Fouré, Alexandre; Guye, Maxime; Bendahan, David; Attarian, Shahram

2017-01-01

Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common hereditary muscular disorders. Currently FSHD has no known effective treatment and detailed data on the natural history are lacking. Determination of the efficacy of a given therapeutic approach might be difficult in FSHD given the slow and highly variable disease progression. Magnetic resonance imaging (MRI) has been widely used to qualitatively and quantitatively evaluate in vivo the muscle alterations in various neuromuscular disorders. The main aim of the present study was to investigate longitudinally the time-dependent changes occurring in thigh muscles of FSHD patients using quantitative MRI and to assess the potential relationships with the clinical findings. Thirty-five FSHD1 patients (17 females) were enrolled. Clinical assessment tools including manual muscle testing using medical research council score (MRC), and motor function measure (MFM) were recorded each year for a period ranging from 1 to 2 years. For the MRI measurements, we used a new quantitative index, i.e., the mean pixel intensity (MPI) calculated from the pixel-intensity distribution in T1 weighted images. The corresponding MPI scores were calculated for each thigh, for each compartment and for both thighs totally (MPItotal). The total mean pixel intensity (MPItotal) refers to the sum of each pixel signal intensity divided by the corresponding number of pixels. An increased MPItotal indicates both a raised fat infiltration together with a reduced muscle volume thereby illustrating disease progression. Clinical scores did not change significantly over time whereas MPItotal increased significantly from an initial averaged value of 39.6 to 41.1 with a corresponding rate of 0.62/year. While clinical scores and MPItotal measured at the start of the study were significantly related, no correlation was found between the rate of MPItotal and MRC sum score changes, MFMtotal and MFM subscores. The relative rate of MPItotal

Human airway epithelial cell cultures for modeling respiratory syncytial virus infection.

PubMed

Pickles, Raymond J

2013-01-01

Respiratory syncytial virus (RSV) is an important human respiratory pathogen with narrow species tropism. Limited availability of human pathologic specimens during early RSV-induced lung disease and ethical restrictions for RSV challenge studies in the lower airways of human volunteers has slowed our understanding of how RSV causes airway disease and greatly limited the development of therapeutic strategies for reducing RSV disease burden. Our current knowledge of RSV infection and pathology is largely based on in vitro studies using nonpolarized epithelial cell-lines grown on plastic or in vivo studies using animal models semipermissive for RSV infection. Although these models have revealed important aspects of RSV infection, replication, and associated inflammatory responses, these models do not broadly recapitulate the early interactions and potential consequences of RSV infection of the human columnar airway epithelium in vivo. In this chapter, the pro et contra of in vitro models of human columnar airway epithelium and their usefulness in respiratory virus pathogenesis and vaccine development studies will be discussed. The use of such culture models to predict characteristics of RSV infection and the correlation of these findings to the human in vivo situation will likely accelerate our understanding of RSV pathogenesis potentially identifying novel strategies for limiting the severity of RSV-associated airway disease.

Application of Posterior Thigh Three-Dimensional Profunda Artery Perforator Perforasomes in Refining Next-Generation Flap Designs: Transverse, Vertical, and S-Shaped Profunda Artery Perforator Flaps.

PubMed

Mohan, Anita T; Zhu, Lin; Sur, Yoo Joon; Morsy, Mohamed; Michalak, Gregory J; Lachman, Nirusha; Rammos, Charalambos K; Saint-Cyr, Michel

2017-04-01

This study aimed to delineate and compare the hot spots and three-dimensional vascular territories of dominant profunda artery perforators in the posterior thigh region, and modifications in flap design are discussed. Twenty-nine posterior thigh flaps were raised in fresh cadaveric specimens, and profunda artery perforators were documented. Dominant perforators were injected with iodinated contrast to assess perforasomes using computed tomographic angiography. Analysis with three-dimensional rendering and volume calculations of perfusion patterns was performed. In total, 316 perforators were mapped and 33 perforators were injected for analysis. The hot spot for dominant perforators was the proximal medial quadrant, 5 to 10 cm from the inferior gluteal crease, with two smaller hot spots in the upper lateral and distal posterior midline. Although 69 percent were musculocutaneous, distal perforators were predominantly septocutaneous in the posterior midline, 5 to 8 cm from the popliteal crease. Proximal perforators were classified into first (most proximal) and second perforators, and their median perforasome was 233 and 286.4 cm, respectively (p = 0.86). There were no significant differences between proximal and distal perforators in perforasome surface areas, percentage areas perfused, and perforasome volumes. Large linking vessel networks were attributed to a broader perforasome and greater overlap between adjacent or distal perforators. Dominant linking vessels and recurrent flow through the subdermal plexus contribute to the robust vascular supply of profunda artery perforator flaps. Posterior thigh region perforator hot spots and their perfusion characteristics can inform the potential limits, orientation, and modifications of flap or skin paddle designs.

Modified Design of Anterolateral Thigh Flap for Total Pharyngolaryngectomy Reconstruction: A Single-Center Experience.

PubMed

Cheng, Li-Yen; Chen, Cha-Chun; Lin, Hwang-Chi; Jeng, Chu-Hsu; Lin, Shang-Hsi; Chen, Wei-Nung Jim; Lin, Yu-Hsien; Hao, Sheng-Po

2018-07-01

Defects after total pharyngolaryngectomy for hypopharyngeal cancer often require reconstruction via free tissue transfer. Recently, anterolateral thigh (ALT) flap has become the gold standard in many centers because of its advantages with respect to versatility, minimal donor-site morbidity, good speech quality, and relatively low fistula and anastomotic leakage rates. Moreover, ALT allows 2 surgical teams to work simultaneously. However, the height of the parallelogram in the ALT design for neoesophagus reconstruction is usually set at a minimum of 9.4 cm (circumference, 2πr) for smooth food passage. Because this height exceeds 8 cm, the donor site may not be closed primarily, which highly depends on the patient's body habitus and the skin tone or quality and requires other methods, such as local flap or skin graft for wound closure, which subsequently increase operating time and donor-site complication rate. Thus, we aimed to construct a simple and modified ALT design that will not only include the advantages described earlier but also provide adequate donor-site primary closure without jeopardizing complication rates. Ten patients with hypopharyngeal cancer underwent reconstructive surgery using our modified ALT design after total pharyngolaryngectomy between 2010 and 2017. Our modified ALT design converts this "classical" shape into a parallelogram so that the height of the modified design is always less than 8 cm, thus allowing for easy primary closure of the wound. The donor-site defects of all 10 patients were closed primarily. No donor-site complications and partial or total flap loss were observed. One patient experienced persistent wound infection with dehiscence, for which debridement was performed. The stricture and fistula rates were 10% (n = 1) and 20% (n = 2), respectively. The mean follow-up time is approximately 1 year. Minimizing donor-site morbidity is an important goal in reconstructive surgery. Our modified ALT flap design is simple, enabling

The Development of Statistical Models for Predicting Surgical Site Infections in Japan: Toward a Statistical Model-Based Standardized Infection Ratio.

PubMed

Fukuda, Haruhisa; Kuroki, Manabu

2016-03-01

To develop and internally validate a surgical site infection (SSI) prediction model for Japan. Retrospective observational cohort study. We analyzed surveillance data submitted to the Japan Nosocomial Infections Surveillance system for patients who had undergone target surgical procedures from January 1, 2010, through December 31, 2012. Logistic regression analyses were used to develop statistical models for predicting SSIs. An SSI prediction model was constructed for each of the procedure categories by statistically selecting the appropriate risk factors from among the collected surveillance data and determining their optimal categorization. Standard bootstrapping techniques were applied to assess potential overfitting. The C-index was used to compare the predictive performances of the new statistical models with those of models based on conventional risk index variables. The study sample comprised 349,987 cases from 428 participant hospitals throughout Japan, and the overall SSI incidence was 7.0%. The C-indices of the new statistical models were significantly higher than those of the conventional risk index models in 21 (67.7%) of the 31 procedure categories (P<.05). No significant overfitting was detected. Japan-specific SSI prediction models were shown to generally have higher accuracy than conventional risk index models. These new models may have applications in assessing hospital performance and identifying high-risk patients in specific procedure categories.

From in vitro to in vivo Models of Bacterial Biofilm-Related Infections

PubMed Central

Lebeaux, David; Chauhan, Ashwini; Rendueles, Olaya; Beloin, Christophe

2013-01-01

The influence of microorganisms growing as sessile communities in a large number of human infections has been extensively studied and recognized for 30–40 years, therefore warranting intense scientific and medical research. Nonetheless, mimicking the biofilm-life style of bacteria and biofilm-related infections has been an arduous task. Models used to study biofilms range from simple in vitro to complex in vivo models of tissues or device-related infections. These different models have progressively contributed to the current knowledge of biofilm physiology within the host context. While far from a complete understanding of the multiple elements controlling the dynamic interactions between the host and biofilms, we are nowadays witnessing the emergence of promising preventive or curative strategies to fight biofilm-related infections. This review undertakes a comprehensive analysis of the literature from a historic perspective commenting on the contribution of the different models and discussing future venues and new approaches that can be merged with more traditional techniques in order to model biofilm-infections and efficiently fight them. PMID:25437038

Longitudinal (4 year) change of thigh muscle and adipose tissue distribution in chronically painful vs. painless knees – data from the Osteoarthritis Initiative

PubMed Central

Ruhdorfer, Anja; Wirth, Wolfgang; Dannhauer, Torben; Eckstein, Felix

2015-01-01

Objective To evaluate 4-year longitudinal change in thigh muscle and adipose tissue content in chronically painful versus painless knees. Methods Knees from Osteoarthritis Initiative participants with non-acceptable symptom status (numerical rating scale ≥4) and frequent pain (≥6 months at baseline, year 2 and year 4 follow-up) were studied. These were matched with painless controls (bilateral NRS pain intensity≤1 and ≤infrequent pain at all 3 timepoints). 4-year longitudinal changes in thigh muscle anatomical cross-sectional areas (CSAs), isometric muscle strength, and in subcutaneous (SCF) and intermuscular fat (IMF) CSAs were obtained from magnetic resonance images (MRI) and were compared between groups (paired t-tests). Results 43 participants fulfilled the inclusion criteria of chronic pain, had complete thigh muscle MRI acquisitions and strength measurements, and a matched control. Quadriceps CSAs, but not extensor strength, showed a significant longitudinal decrease in chronically painful knees (-3.9%; 95%confidence interval [95 CI] -6.3%,-1.5%) and in painless controls (-2.4%; 95% CI -4.1%, -0.7%); the difference in change was not statistically significant (p=0.33). There was a significant 4-year gain in SCF in painful knees (8.1%; 95% CI 3.1%, 13%) but not in controls (0.0%; 95%CI -4.4%, +4.4%) with the difference in change being significant (p=0.03). The gain in IMF (∼5.2%) was similar between painful and painless knees. Conclusion This is the first paper to show a significant impact of (chronic) knee pain on longitudinal change in local subcutaneous adipose tissue. The effect of pain on subcutaneous fat appeared stronger than that on intermuscular adipose tissue and on muscle status. PMID:25887367

Block effect on HCV infection by HMGB1 released from virus-infected cells: An insight from mathematical modeling

NASA Astrophysics Data System (ADS)

Wang, Wei; Ma, Wanbiao

2018-06-01

The nuclear protein high-mobility group box 1 (HMGB1) can have an active role in deoxyribonucleic acid (DNA) organization and the regulation of transcription. Based on the new findings from a recent experimental study, the blocking effect on HCV infection by HMGB1 released from virus-infected cells is investigated using a diffusive model for viral infection dynamics. In the model, the diffusion of the virus depends not only on its concentration gradient, but also on the concentration of HMGB1. The basic reproduction number, threshold dynamics, stability properties of the steady states, travelling wave solutions, and spreading speed for the proposed model are studied. We show that the HMGB1-induced blocking of HCV infection slows the spread of virus compared with random diffusion only. Numerically, it is shown that a high concentration of HMGB1 can block the spread of virus and this confirms, not only qualitatively but also quantitatively, the experimental result.

Mouse model for sublethal Leptospira interrogans infection.

PubMed

Richer, Luciana; Potula, Hari-Hara; Melo, Rita; Vieira, Ana; Gomes-Solecki, Maria

2015-12-01

Although Leptospira can infect a wide range of mammalian species, most studies have been conducted in golden Syrian hamsters, a species particularly sensitive to acute disease. Chronic disease has been well characterized in the rat, one of the natural reservoir hosts. Studies in another asymptomatic reservoir host, the mouse, have occasionally been done and have limited infection to mice younger than 6 weeks of age. We analyzed the outcome of sublethal infection of C3H/HeJ mice older than age 10 weeks with Leptospira interrogans serovar Copenhageni. Infection led to bloodstream dissemination of Leptospira, which was followed by urinary shedding, body weight loss, hypothermia, and colonization of the kidney by live spirochetes 2 weeks after infection. In addition, Leptospira dissemination triggered inflammation in the kidney but not in the liver or lung, as determined by increased levels of mRNA transcripts for the keratinocyte-derived chemokine, RANTES, macrophage inflammatory protein 2, tumor necrosis factor alpha, interleukin-1β, inducible nitric oxide synthase, interleukin-6, and gamma interferon in kidney tissue. The acquired humoral response to Leptospira infection led to the production of IgG mainly of the IgG1 subtype. Flow cytometric analysis of splenocytes from infected mice revealed that cellular expansion was primarily due to an increase in the levels of CD4(+) and double-negative T cells (not CD8(+) cells) and that CD4(+) T cells acquired a CD44(high) CD62L(low) effector phenotype not accompanied by increases in memory T cells. A mouse model for sublethal Leptospira infection allows understanding of the bacterial and host factors that lead to immune evasion, which can result in acute or chronic disease or resistance to infection (protection). Copyright © 2015, American Society for Microbiology. All Rights Reserved.

An Immunocompetent Mouse Model of Zika Virus Infection.

PubMed

Gorman, Matthew J; Caine, Elizabeth A; Zaitsev, Konstantin; Begley, Matthew C; Weger-Lucarelli, James; Uccellini, Melissa B; Tripathi, Shashank; Morrison, Juliet; Yount, Boyd L; Dinnon, Kenneth H; Rückert, Claudia; Young, Michael C; Zhu, Zhe; Robertson, Shelly J; McNally, Kristin L; Ye, Jing; Cao, Bin; Mysorekar, Indira U; Ebel, Gregory D; Baric, Ralph S; Best, Sonja M; Artyomov, Maxim N; Garcia-Sastre, Adolfo; Diamond, Michael S

2018-05-09

Progress toward understanding Zika virus (ZIKV) pathogenesis is hindered by lack of immunocompetent small animal models, in part because ZIKV fails to effectively antagonize Stat2-dependent interferon (IFN) responses in mice. To address this limitation, we first passaged an African ZIKV strain (ZIKV-Dak-41525) through Rag1 -/- mice to obtain a mouse-adapted virus (ZIKV-Dak-MA) that was more virulent than ZIKV-Dak-41525 in mice treated with an anti-Ifnar1 antibody. A G18R substitution in NS4B was the genetic basis for the increased replication, and resulted in decreased IFN-β production, diminished IFN-stimulated gene expression, and the greater brain infection observed with ZIKV-Dak-MA. To generate a fully immunocompetent mouse model of ZIKV infection, human STAT2 was introduced into the mouse Stat2 locus (hSTAT2 KI). Subcutaneous inoculation of pregnant hSTAT2 KI mice with ZIKV-Dak-MA resulted in spread to the placenta and fetal brain. An immunocompetent mouse model of ZIKV infection may prove valuable for evaluating countermeasures to limit disease. Copyright © 2018 Elsevier Inc. All rights reserved.

The Plaque-Antiserum Method: an Assay of Virus Infectivity and an Experimental Model of Virus Infection

PubMed Central

De Flora, Silvio

1974-01-01

Areas of cytopathic effect can be circumscribed in cell monolayers by adding antiserum to the liquid nutrient medium after adsorption of virus. This procedure represents a simple and reliable tool for the titration of virus infectivity and provides an experimental model for studying some aspects of virus infection. Images PMID:4364462

Mathematical modeling of transmission co-infection tuberculosis in HIV community

NASA Astrophysics Data System (ADS)

Lusiana, V.; Putra, P. S.; Nuraini, N.; Soewono, E.

2017-03-01

TB and HIV infection have the effect of deeply on assault the immune system, since they can afford to weaken host immune respone through a mechanism that has not been fully understood. HIV co-infection is the stongest risk factor for progression of M. tuberculosis to active TB disease in HIV individuals, as well as TB has been accelerated to progression HIV infection. In this paper we create a model of transmission co-infection TB in HIV community, dynamic system with ten compartments built in here. Dynamic analysis in this paper mentioned ranging from disease free equilibrium conditions, endemic equilibrium conditions, basic reproduction ratio, stability analysis and numerical simulation. Basic reproductive ratio were obtained from spectral radius the next generation matrix of the model. Numerical simulations are built to justify the results of the analysis and to see the changes in the dynamics of the population in each compartment. The sensitivity analysis indicates that the parameters affecting the population dynamics of TB in people with HIV infection is parameters rate of progression of individuals from the exposed TB class to the active TB, treatment rate of exposed TB individuals, treatment rate of infectious (active TB) individuals and probability of transmission of TB infection from an infective to a susceptible per contact per unit time. We can conclude that growing number of infections carried by infectious TB in people with HIV infection can lead to increased spread of disease or increase in endemic conditions.

Blockade of epithelial membrane protein 2 (EMP2) abrogates infection of Chlamydia muridarum murine genital infection model

PubMed Central

Shimazaki, Kaori; Chan, Ann M.; Moniz, Raymond J.; Wadehra, Madhuri; Nagy, Agnes; Coulam, C. Paige; Mareninov, Sergey; Lepin, Eric M.; Wu, Anna M.; Kelly, Kathleen A.; Braun, Jonathan; Gordon, Lynn K.

2012-01-01

New methods are needed to eradicate or prevent Chlamydia trachomatis infections. Blockade of epithelial membrane protein 2 (EMP2) by genetic silencing or neutralizing polyclonal antibody reduced chlamydial infectivity in vitro. This study tests the prediction that recombinant anti-EMP2 diabody could reduce early chlamydial infection of the genital tract in vivo. In a murine infection model, pretreatment with anti-EMP2 diabody, as compared to control diabody, significantly reduced bacterial load, tissue production of inflammatory cytokines, recruitment of polymorphonuclear leukocytes, and local tissue inflammation. These findings support EMP2 as a potential preventative and therapeutic target for genital chlamydial infection. PMID:19159428

Concurrent agreement between an anthropometric model to predict thigh volume and dual-energy X-Ray absorptiometry assessment in female volleyball players aged 14-18 years.

PubMed

Tavares, Óscar M; Valente-Dos-Santos, João; Duarte, João P; Póvoas, Susana C; Gobbo, Luís A; Fernandes, Rômulo A; Marinho, Daniel A; Casanova, José M; Sherar, Lauren B; Courteix, Daniel; Coelho-E-Silva, Manuel J

2016-11-24

A variety of performance outputs are strongly determined by lower limbs volume and composition in children and adolescents. The current study aimed to examine the validity of thigh volume (TV) estimated by anthropometry in late adolescent female volleyball players. Dual-energy X-ray absorptiometry (DXA) measures were used as the reference method. Total and regional body composition was assessed with a Lunar DPX NT/Pro/MD+/Duo/Bravo scanner in a cross-sectional sample of 42 Portuguese female volleyball players aged 14-18 years (165.2 ± 0.9 cm; 61.1 ± 1.4 kg). TV was estimated with the reference method (TV-DXA) and with the anthropometric method (TV-ANTH). Agreement between procedures was assessed with Deming regression. The analysis also considered a calibration of the anthropometric approach. The equation that best predicted TV-DXA was: -0.899 + 0.876 × log 10 (body mass) + 0.113 × log 10 (TV-ANTH). This new model (NM) was validated using the predicted residual sum of squares (PRESS) method (R 2 PRESS  = 0.838). Correlation between the reference method and the NM was 0.934 (95%CI: 0.880-0.964, S y∙x  = 0.325 L). A new and accurate anthropometric method to estimate TV in adolescent female volleyball players was obtained from the equation of Jones and Pearson alongside with adjustments for body mass.

Models for the study of Clostridium difficile infection

PubMed Central

Best, Emma L.; Freeman, Jane; Wilcox, Mark H.

2012-01-01

Models of Clostridium difficile infection (C. difficile) have been used extensively for Clostridium difficile (C. difficile) research. The hamster model of C. difficile infection has been most extensively employed for the study of C. difficile and this has been used in many different areas of research, including the induction of C. difficile, the testing of new treatments, population dynamics and characterization of virulence. Investigations using in vitro models for C. difficile introduced the concept of colonization resistance, evaluated the role of antibiotics in C. difficile development, explored population dynamics and have been useful in the evaluation of C. difficile treatments. Experiments using models have major advantages over clinical studies and have been indispensible in furthering C. difficile research. It is important for future study programs to carefully consider the approach to use and therefore be better placed to inform the design and interpretation of clinical studies. PMID:22555466

Animal Models of Zika Virus Infection, Pathogenesis, and Immunity

PubMed Central

2017-01-01

ABSTRACT Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that now causes epidemics affecting millions of people on multiple continents. The virus has received global attention because of some of its unusual epidemiological and clinical features, including persistent infection in the male reproductive tract and sexual transmission, an ability to cross the placenta during pregnancy and infect the developing fetus to cause congenital malformations, and its association with Guillain-Barré syndrome in adults. This past year has witnessed an intensive effort by the global scientific community to understand the biology of ZIKV and to develop pathogenesis models for the rapid testing of possible countermeasures. Here, we review the recent advances in and utility and limitations of newly developed mouse and nonhuman primate models of ZIKV infection and pathogenesis. PMID:28148798

[Prediction of schistosomiasis infection rates of population based on ARIMA-NARNN model].

PubMed

Ke-Wei, Wang; Yu, Wu; Jin-Ping, Li; Yu-Yu, Jiang

2016-07-12

To explore the effect of the autoregressive integrated moving average model-nonlinear auto-regressive neural network (ARIMA-NARNN) model on predicting schistosomiasis infection rates of population. The ARIMA model, NARNN model and ARIMA-NARNN model were established based on monthly schistosomiasis infection rates from January 2005 to February 2015 in Jiangsu Province, China. The fitting and prediction performances of the three models were compared. Compared to the ARIMA model and NARNN model, the mean square error (MSE), mean absolute error (MAE) and mean absolute percentage error (MAPE) of the ARIMA-NARNN model were the least with the values of 0.011 1, 0.090 0 and 0.282 4, respectively. The ARIMA-NARNN model could effectively fit and predict schistosomiasis infection rates of population, which might have a great application value for the prevention and control of schistosomiasis.

Routine preoperative colour Doppler duplex ultrasound scanning in anterolateral thigh flaps.

PubMed

Lichte, Johanna; Teichmann, Jan; Loberg, Christina; Kloss-Brandstätter, Anita; Bartella, Alexander; Steiner, Timm; Modabber, Ali; Hölzle, Frank; Lethaus, Bernd

2016-10-01

The anterolateral thigh flap (ALT) is often used to reconstruct the head and neck and depends on one or more skin perforators, which often present with variable anatomy. The aim of this study was to localise and evaluate the precise position of these perforators preoperatively with colour Doppler duplex ultrasound scanning (US). We detected 74 perforators in 30 patients. The mean duration of examination with colour Doppler was 29 (range 13-51) minutes. Adequate perforators and their anatomical course could be detected preoperatively extremely accurately (p<0.001). The mean difference between the preoperatively marked, and the real, positions was 6.3 (range 0-16) mm. There was a highly significant correlation between the accuracy of the prediction and the body mass index of the patient (0.75; p<0.001). Neither the age nor the sex of the patient correlated with the accuracy of the prediction. Colour Doppler duplex US used preoperatively to localise perforators in ALT flaps is reliable and could be adopted as standard procedure. Copyright © 2016 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Exploring the Pregnant Guinea Pig as a Model for Group B Streptococcus Intrauterine Infection.

PubMed

Harrell, Maria I; Burnside, Kellie; Whidbey, Christopher; Vornhagen, Jay; Adams Waldorf, Kristina M; Rajagopal, Lakshmi

2017-09-01

Infection of the amniotic cavity remains a major cause of preterm birth, stillbirth, fetal injury and early onset, fulminant infections in newborns. Currently, there are no effective therapies to prevent in utero infection and consequent co-morbidities. This is in part due to the lack of feasible and appropriate animal models to understand mechanisms that lead to in utero infections. Use of mouse and rat models do not fully recapitulate human pregnancy, while pregnant nonhuman primate models are limited by ethical considerations, technical constraints, and cost. Given these limitations, the guinea pig is an attractive animal model for studying pregnancy infections, particularly as the placental structure is quite similar to the human placenta. Here, we describe our studies that explored the pregnant guinea pig as a model to study in utero Group B Streptococci (GBS) infections. We observed that intrauterine inoculation of wild type GBS in pregnant guinea pigs resulted in bacterial invasion and dissemination to the placenta, amniotic fluid and fetal organs. Also, hyperhemolytic GBS such as those lacking the hemolysin repressor CovR/S showed increased dissemination into the amniotic fluid and fetal organs such as the fetal lung and brain. These results are similar to those observed in mouse and non-human primate models of in utero infection, and support use of the guinea pig as a model for studying GBS infections in pregnancy.

Comparison of linear and non-linear models for predicting energy expenditure from raw accelerometer data.

PubMed

Montoye, Alexander H K; Begum, Munni; Henning, Zachary; Pfeiffer, Karin A

2017-02-01

This study had three purposes, all related to evaluating energy expenditure (EE) prediction accuracy from body-worn accelerometers: (1) compare linear regression to linear mixed models, (2) compare linear models to artificial neural network models, and (3) compare accuracy of accelerometers placed on the hip, thigh, and wrists. Forty individuals performed 13 activities in a 90 min semi-structured, laboratory-based protocol. Participants wore accelerometers on the right hip, right thigh, and both wrists and a portable metabolic analyzer (EE criterion). Four EE prediction models were developed for each accelerometer: linear regression, linear mixed, and two ANN models. EE prediction accuracy was assessed using correlations, root mean square error (RMSE), and bias and was compared across models and accelerometers using repeated-measures analysis of variance. For all accelerometer placements, there were no significant differences for correlations or RMSE between linear regression and linear mixed models (correlations: r  =  0.71-0.88, RMSE: 1.11-1.61 METs; p  >  0.05). For the thigh-worn accelerometer, there were no differences in correlations or RMSE between linear and ANN models (ANN-correlations: r  =  0.89, RMSE: 1.07-1.08 METs. Linear models-correlations: r  =  0.88, RMSE: 1.10-1.11 METs; p  >  0.05). Conversely, one ANN had higher correlations and lower RMSE than both linear models for the hip (ANN-correlation: r  =  0.88, RMSE: 1.12 METs. Linear models-correlations: r  =  0.86, RMSE: 1.18-1.19 METs; p  <  0.05), and both ANNs had higher correlations and lower RMSE than both linear models for the wrist-worn accelerometers (ANN-correlations: r  =  0.82-0.84, RMSE: 1.26-1.32 METs. Linear models-correlations: r  =  0.71-0.73, RMSE: 1.55-1.61 METs; p  <  0.01). For studies using wrist-worn accelerometers, machine learning models offer a significant improvement in EE prediction

Denture-associated biofilm infection in three-dimensional oral mucosal tissue models.

PubMed

Morse, Daniel J; Wilson, Melanie J; Wei, Xiaoqing; Lewis, Michael A O; Bradshaw, David J; Murdoch, Craig; Williams, David W

2018-03-01

In vitro analyses of virulence, pathogenicity and associated host cell responses are important components in the study of biofilm infections. The Candida-related infection, denture-associated oral candidosis, affects up to 60 % of denture wearers and manifests as inflammation of palatal tissues contacting the denture-fitting surface. Commercially available three-dimensional tissue models can be used to study infection, but their use is limited for many academic research institutions, primarily because of the substantial purchase costs. The aim of this study was to develop and evaluate the use of in vitro tissue models to assess infections by biofilms on acrylic surfaces through tissue damage and Candida albicans virulence gene expression. In vitro models were compared against commercially available tissue equivalents (keratinocyte-only, SkinEthic; full-thickness, MatTek Corporation). An in vitro keratinocyte-only tissue was produced using a cancer-derived cell line, TR146, and a full-thickness model incorporating primary fibroblasts and immortalised normal oral keratinocytes was also generated. The in vitro full-thickness tissues incorporated keratinocytes and fibroblasts, and have potential for future further development and analysis. Following polymicrobial infection with biofilms on acrylic surfaces, both in-house developed models were shown to provide equivalent results to the SkinEthic and MatTek models in terms of tissue damage: a significant (P<0.05) increase in LDH activity for mixed species biofilms compared to uninfected control, and no significant difference (P>0.05) in the expression of most C. albicans virulence genes when comparing tissue models of the same type. Our results confirm the feasibility and suitability of using these alternative in vitro tissue models for such analyses.

Predictive models of control strategies involved in containing indoor airborne infections.

PubMed

Chen, S-C; Chang, C-F; Liao, C-M

2006-12-01

Recently developed control measure modeling approaches for containing airborne infections, including engineering controls with respiratory protection and public health interventions, are readily amenable to an integrated-scale analysis. Here we show that such models can be derived from an integrated-scale analysis generated from three different types of functional relationship: Wells-Riley mathematical model, competing-risks model, and Von Foerster equation, both of the key epidemiological determinants involved and of the functional connections between them. We examine mathematically the impact of engineering control measures such as enhanced air exchange and air filtration rates with personal masking combined with public health interventions such as vaccination, isolation, and contact tracing in containing the spread of indoor airborne infections including influenza, chickenpox, measles, and severe acute respiratory syndrome (SARS). If enhanced engineering controls could reduce the basic reproductive number (R0) below 1.60 for chickenpox and 3 for measles, our simulations show that in such a prepared response with public health interventions would have a high probability of containing the indoor airborne infections. Combinations of engineering control measures and public health interventions could moderately contain influenza strains with an R0 as high as 4. Our analysis indicates that effective isolation of symptomatic patients with low-efficacy contact tracing is sufficient to control a SARS outbreak. We suggest that a valuable added dimension to public health inventions could be provided by systematically quantifying transmissibility and proportion of asymptomatic infection of indoor airborne infection. Practical Implications We have developed a flexible mathematical model that can help determine the best intervention strategies for containing indoor airborne infections. The approach presented here is scalable and can be extended to include additional control

Human immune system mouse models of Ebola virus infection.

PubMed

Spengler, Jessica R; Prescott, Joseph; Feldmann, Heinz; Spiropoulou, Christina F

2017-08-01

Human immune system (HIS) mice, immunodeficient mice engrafted with human cells (with or without donor-matched tissue), offer a unique opportunity to study pathogens that cause disease predominantly or exclusively in humans. Several HIS mouse models have recently been used to study Ebola virus (EBOV) infection and disease. The results of these studies are encouraging and support further development and use of these models in Ebola research. HIS mice provide a small animal model to study EBOV isolates, investigate early viral interactions with human immune cells, screen vaccines and therapeutics that modulate the immune system, and investigate sequelae in survivors. Here we review existing models, discuss their use in pathogenesis studies and therapeutic screening, and highlight considerations for study design and analysis. Finally, we point out caveats to current models, and recommend future efforts for modeling EBOV infection in HIS mice. Published by Elsevier B.V.

Murine model for congenital CMV infection and hearing impairment

PubMed Central

2011-01-01

Background Congenital cytomegalovirus (CMV) infection is the leading cause of sensorineural hearing loss (SNHL), and SNHL is the most frequent sequela of congenital CMV infection. But the pathogenic mechanism remains unknown, and there is no ideal CMV intrauterine infection animal model to study the mechanisms by which SNHL develops. Methods We established the congenital murine cytomegalovirus (MCMV) infection model by directly injecting the virus into the placenta on day 12.5 of gestation. Then, we observed the development and the MCMV congenital infection rate of the fetuses on the day they were born. Furthermore, we detected the auditory functions, the conditions of the MCMV infection, and the histological change of the inner ears of 28-day-old and 70-day-old offspring. Results Both the fetal loss rate and the teratism rate of offspring whose placentas were inoculated with MCMV increased, and their body length, head circumference, and weight decreased. The hearing level of offspring both decreased at both 28- and 70-days post birth; the 70-day-old mice developed lower hearing levels than did the 28-day old mice. No significant inflammatory changes in the cochleae of the mice were observed. MCMV DNA signals were mainly detected in the spiral ganglion neurons and the endolymph area, but not in the perilymph area. The number of neurons decreased, and their ultrastructures changed. Moreover, with age, the number of neurons dramatically decreased, and the ultrastructural lesions of neurons became much more severe. Conclusions The results suggest that the direct injection of MCMV into the placenta may efficiently cause fetal infection and disturb the intrauterine development of the fetus, and placental inoculation itself has no obvious adverse effects on offspring. The reduction in the number of spiral ganglion neurons and the ultrastructural lesions of the neurons may be the major cause of congenital CMV infection-induced progressive SNHL. PMID:21320351

Murine model for congenital CMV infection and hearing impairment.

PubMed

Juanjuan, Chen; Yan, Feng; Li, Chen; Haizhi, Liu; Ling, Wang; Xinrong, Wang; Juan, Xiao; Tao, Liu; Zongzhi, Yin; Suhua, Chen

2011-02-15

Congenital cytomegalovirus (CMV) infection is the leading cause of sensorineural hearing loss (SNHL), and SNHL is the most frequent sequela of congenital CMV infection. But the pathogenic mechanism remains unknown, and there is no ideal CMV intrauterine infection animal model to study the mechanisms by which SNHL develops. We established the congenital murine cytomegalovirus (MCMV) infection model by directly injecting the virus into the placenta on day 12.5 of gestation. Then, we observed the development and the MCMV congenital infection rate of the fetuses on the day they were born. Furthermore, we detected the auditory functions, the conditions of the MCMV infection, and the histological change of the inner ears of 28-day-old and 70-day-old offspring. Both the fetal loss rate and the teratism rate of offspring whose placentas were inoculated with MCMV increased, and their body length, head circumference, and weight decreased. The hearing level of offspring both decreased at both 28- and 70-days post birth; the 70-day-old mice developed lower hearing levels than did the 28-day old mice. No significant inflammatory changes in the cochleae of the mice were observed. MCMV DNA signals were mainly detected in the spiral ganglion neurons and the endolymph area, but not in the perilymph area. The number of neurons decreased, and their ultrastructures changed. Moreover, with age, the number of neurons dramatically decreased, and the ultrastructural lesions of neurons became much more severe. The results suggest that the direct injection of MCMV into the placenta may efficiently cause fetal infection and disturb the intrauterine development of the fetus, and placental inoculation itself has no obvious adverse effects on offspring. The reduction in the number of spiral ganglion neurons and the ultrastructural lesions of the neurons may be the major cause of congenital CMV infection-induced progressive SNHL.

Usefulness of the anterolateral thigh flap with vascularized fascia lata for reconstruction of orbital floor and nasal surface after total maxillectomy.

PubMed

Joo, Young-Hoon; Cho, Kwang-Jae; Park, Jun-Ook; Kim, Min-Sik

2013-09-01

The aim of this study was to describe a technique using the fascia lata (FL) component of the anterolateral thigh (ALT) flap to re-create the orbital floor and lateral nasal wall after total maxillectomy. Retrospective analysis of medical records. A total of 22 patients underwent maxillary reconstruction using a composite ALT-FL flap following cancer resection. All patients underwent total maxillectomies via the Weber-Ferguson approach. The ALT flap was harvested with the deep fascia of the thigh with the aim of using it for lining of the orbital floor and lateral nasal cavity. The FL was sutured to the palatine bone inferiorly, nasal bone and zygomatic bone superiorly, and nasopharyngeal mucosa posteriorly to provide an orbital floor and make a neonasal cavity. There was 100% free flap survival. Speech was normal in eight (36%) patients, near normal in 10 (46%), and intelligible in four (18%). Seventeen (77%) patients gained a good facial appearance, and five (23%) a fair appearance. Sixteen (73%) patients complained of mild nasal crust formation, and the rest (27%) developed moderate crust. Microvascular reconstruction using a composite ALT-FL flap provided a reliable fascial component for orbital floor and nasal surface reconstruction of total maxillectomy defects. Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

Animal Models of Zika Virus Infection, Pathogenesis, and Immunity.

PubMed

Morrison, Thomas E; Diamond, Michael S

2017-04-15

Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that now causes epidemics affecting millions of people on multiple continents. The virus has received global attention because of some of its unusual epidemiological and clinical features, including persistent infection in the male reproductive tract and sexual transmission, an ability to cross the placenta during pregnancy and infect the developing fetus to cause congenital malformations, and its association with Guillain-Barré syndrome in adults. This past year has witnessed an intensive effort by the global scientific community to understand the biology of ZIKV and to develop pathogenesis models for the rapid testing of possible countermeasures. Here, we review the recent advances in and utility and limitations of newly developed mouse and nonhuman primate models of ZIKV infection and pathogenesis. Copyright © 2017 American Society for Microbiology.

Use of Galleria mellonella as a model organism to study Legionella pneumophila infection.

PubMed

Harding, Clare R; Schroeder, Gunnar N; Collins, James W; Frankel, Gad

2013-11-22

Legionella pneumophila, the causative agent of a severe pneumonia named Legionnaires' disease, is an important human pathogen that infects and replicates within alveolar macrophages. Its virulence depends on the Dot/Icm type IV secretion system (T4SS), which is essential to establish a replication permissive vacuole known as the Legionella containing vacuole (LCV). L. pneumophila infection can be modeled in mice however most mouse strains are not permissive, leading to the search for novel infection models. We have recently shown that the larvae of the wax moth Galleria mellonella are suitable for investigation of L. pneumophila infection. G. mellonella is increasingly used as an infection model for human pathogens and a good correlation exists between virulence of several bacterial species in the insect and in mammalian models. A key component of the larvae's immune defenses are hemocytes, professional phagocytes, which take up and destroy invaders. L. pneumophila is able to infect, form a LCV and replicate within these cells. Here we demonstrate protocols for analyzing L. pneumophila virulence in the G. mellonella model, including how to grow infectious L. pneumophila, pretreat the larvae with inhibitors, infect the larvae and how to extract infected cells for quantification and immunofluorescence microscopy. We also describe how to quantify bacterial replication and fitness in competition assays. These approaches allow for the rapid screening of mutants to determine factors important in L. pneumophila virulence, describing a new tool to aid our understanding of this complex pathogen.

A quantitative model for dermal infection and oedema in BALB/c mice pinna.

PubMed

Marino-Marmolejo, Erika Nahomy; Flores-Hernández, Flor Yohana; Flores-Valdez, Mario Alberto; García-Morales, Luis Felipe; González-Villegas, Ana Cecilia; Bravo-Madrigal, Jorge

2016-12-12

Pharmaceutical industry demands innovation for developing new molecules to improve effectiveness and safety of therapeutic medicines. Preclinical assays are the first tests performed to evaluate new therapeutic molecules using animal models. Currently, there are several models for evaluation of treatments, for dermal oedema or infection. However, the most common or usual way is to induce the inflammation with chemical substances instead of infectious agents. On the other hand, this kind of models require the implementation of histological techniques and the interpretation of pathologies to verify the effectiveness of the therapy under assessment. This work was focused on developing a quantitative model of infection and oedema in mouse pinna. The infection was achieved with a strain of Streptococcus pyogenes that was inoculated in an injury induced at the auricle of BALB/c mice, the induced oedema was recorded by measuring the ear thickness with a digital micrometer and histopathological analysis was performed to verify the damage. The presence of S. pyogenes at the infection site was determined every day by culture. Our results showed that S. pyogenes can infect the mouse pinna and that it can be recovered at least for up to 4 days from the infected site; we also found that S. pyogenes can induce a bigger oedema than the PBS-treated control for at least 7 days; our results were validated with an antibacterial and anti-inflammatory formulation made with ciprofloxacin and hydrocortisone. The model we developed led us to emulate a dermal infection and allowed us to objectively evaluate the increase or decrease of the oedema by measuring the thickness of the ear pinna, and to determine the presence of the pathogen in the infection site. We consider that the model could be useful for assessment of new anti-inflammatory or antibacterial therapies for dermal infections.

Tetraodon nigroviridis as a nonlethal model of infectious spleen and kidney necrosis virus (ISKNV) infection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu Xiaopeng; Huang Lichao; Weng Shaoping

Infectious spleen and kidney necrosis virus (ISKNV) is the type species of the genus Megalocytivirus, family Iridoviridae. We have previously established a high mortality ISKNV infection model of zebrafish (Danio rerio). In this study, a nonlethal Tetraodon nigroviridis model of ISKNV infection was established. ISKNV infection did not cause lethal disease in Tetraodon but could infect almost all the organs of this species. Electron microscopy showed ISKNV particles were present in infected tissues. Immunofluorescence and quantitative real-time PCR analysis showed that nearly all the virions and infected cells were cleared at 14 d postinfection. The expression profiles of interferon-{gamma} andmore » tumor necrosis factor-{alpha} gene in response to ISKNV infection were significantly different in Tetraodon and zebrafish. The establishment of the nonlethal Tetraodon model of ISKNV infection can offer a valuable tool complementary to the zebrafish infection model for studying megalocytivirus disease, fish immune systems, and viral tropism.« less

Atypical mycobacteria infection in an immunocompromised patient.

PubMed

Berger, Emily; Batra, Priya; Ralston, Jonathan; Sanchez, Miguel R; Franks, Andrew G

2010-11-15

A 61-year-old woman with systemic lupus erythematosus and Sjögren syndrome presented with a two-month history of symptomatic nodules on the buttocks and thighs that progressed to involve the dorsal aspects of the hands. On examination, infiltrative papules, nodules, and plaques were present in these regions. Biopsy specimens demonstrated granulomatous inflammation and acid-fast bacilli with the use of a Fite stain, although a culture and polymerase chain reaction analysis were negative. The patient continues to improve on long-term clarithromycin therapy. Atypical mycobacterial infections are becoming more common, especially in immunocompromised patients. Antimicrobial therapy, either with a single agent or multiple agents, often is prolonged. A high index of suspicion is warranted in immunocompromised patients, which includes those with connective-tissue diseases that are active or that require immunosuppression. In these patients, the differential diagnosis includes infectious as well as inflammatory, reactive, or neoplastic processes.

Humanized Mouse Models of Epstein-Barr Virus Infection and Associated Diseases

PubMed Central

Fujiwara, Shigeyoshi; Matsuda, Go; Imadome, Ken-Ichi

2013-01-01

Epstein-Barr virus (EBV) is a ubiquitous herpesvirus infecting more than 90% of the adult population of the world. EBV is associated with a variety of diseases including infectious mononucleosis, lymphoproliferative diseases, malignancies such as Burkitt lymphoma and nasopharyngeal carcinoma, and autoimmune diseases including rheumatoid arthritis (RA). EBV in nature infects only humans, but in an experimental setting, a limited species of new-world monkeys can be infected with the virus. Small animal models, suitable for evaluation of novel therapeutics and vaccines, have not been available. Humanized mice, defined here as mice harboring functioning human immune system components, are easily infected with EBV that targets cells of the hematoimmune system. Furthermore, humanized mice can mount both cellular and humoral immune responses to EBV. Thus, many aspects of human EBV infection, including associated diseases (e.g., lymphoproliferative disease, hemophagocytic lymphohistiocytosis and erosive arthritis resembling RA), latent infection, and T-cell-mediated and humoral immune responses have been successfully reproduced in humanized mice. Here we summarize recent achievements in the field of humanized mouse models of EBV infection and show how they have been utilized to analyze EBV pathogenesis and normal and aberrant human immune responses to the virus. PMID:25436886

A novel highly reproducible and lethal nonhuman primate model for orthopox virus infection.

PubMed

Kramski, Marit; Mätz-Rensing, Kerstin; Stahl-Hennig, Christiane; Kaup, Franz-Josef; Nitsche, Andreas; Pauli, Georg; Ellerbrok, Heinz

2010-04-29

The intentional re-introduction of Variola virus (VARV), the agent of smallpox, into the human population is of great concern due its bio-terroristic potential. Moreover, zoonotic infections with Cowpox (CPXV) and Monkeypox virus (MPXV) cause severe diseases in humans. Smallpox vaccines presently available can have severe adverse effects that are no longer acceptable. The efficacy and safety of new vaccines and antiviral drugs for use in humans can only be demonstrated in animal models. The existing nonhuman primate models, using VARV and MPXV, need very high viral doses that have to be applied intravenously or intratracheally to induce a lethal infection in macaques. To overcome these drawbacks, the infectivity and pathogenicity of a particular CPXV was evaluated in the common marmoset (Callithrix jacchus).A CPXV named calpox virus was isolated from a lethal orthopox virus (OPV) outbreak in New World monkeys. We demonstrated that marmosets infected with calpox virus, not only via the intravenous but also the intranasal route, reproducibly develop symptoms resembling smallpox in humans. Infected animals died within 1-3 days after onset of symptoms, even when very low infectious viral doses of 5x10(2) pfu were applied intranasally. Infectious virus was demonstrated in blood, saliva and all organs analyzed.We present the first characterization of a new OPV infection model inducing a disease in common marmosets comparable to smallpox in humans. Intranasal virus inoculation mimicking the natural route of smallpox infection led to reproducible infection. In vivo titration resulted in an MID(50) (minimal monkey infectious dose 50%) of 8.3x10(2) pfu of calpox virus which is approximately 10,000-fold lower than MPXV and VARV doses applied in the macaque models. Therefore, the calpox virus/marmoset model is a suitable nonhuman primate model for the validation of vaccines and antiviral drugs. Furthermore, this model can help study mechanisms of OPV pathogenesis.

A Biomathematical Model of Pneumococcal Lung Infection and Antibiotic Treatment in Mice.

PubMed

Schirm, Sibylle; Ahnert, Peter; Wienhold, Sandra; Mueller-Redetzky, Holger; Nouailles-Kursar, Geraldine; Loeffler, Markus; Witzenrath, Martin; Scholz, Markus

2016-01-01

Pneumonia is considered to be one of the leading causes of death worldwide. The outcome depends on both, proper antibiotic treatment and the effectivity of the immune response of the host. However, due to the complexity of the immunologic cascade initiated during infection, the latter cannot be predicted easily. We construct a biomathematical model of the murine immune response during infection with pneumococcus aiming at predicting the outcome of antibiotic treatment. The model consists of a number of non-linear ordinary differential equations describing dynamics of pneumococcal population, the inflammatory cytokine IL-6, neutrophils and macrophages fighting the infection and destruction of alveolar tissue due to pneumococcus. Equations were derived by translating known biological mechanisms and assuming certain response kinetics. Antibiotic therapy is modelled by a transient depletion of bacteria. Unknown model parameters were determined by fitting the predictions of the model to data sets derived from mice experiments of pneumococcal lung infection with and without antibiotic treatment. Time series of pneumococcal population, debris, neutrophils, activated epithelial cells, macrophages, monocytes and IL-6 serum concentrations were available for this purpose. The antibiotics Ampicillin and Moxifloxacin were considered. Parameter fittings resulted in a good agreement of model and data for all experimental scenarios. Identifiability of parameters is also estimated. The model can be used to predict the performance of alternative schedules of antibiotic treatment. We conclude that we established a biomathematical model of pneumococcal lung infection in mice allowing predictions regarding the outcome of different schedules of antibiotic treatment. We aim at translating the model to the human situation in the near future.

Serum interleukin-6 levels in murine models of Candida albicans infection.

PubMed

Kovács, Renátó; Czudar, Anita; Horváth, László; Szakács, Levente; Majoros, László; Kónya, József

2014-03-01

Two Balb/C mouse models of Candida infection were used to detect serum interleukin-6 (IL-6) responses. The first model used systemic infection by Candida albicans ATCC 10231 strain infected through the lateral tail vein of mice without any specific pretreatment. The median Candida burdens of the kidneys were 1.5 × 106 CFU/ml 24 h postinoculation (p.i.) and 1.2 × 107 CFU/ml 72 h p.i., while median serum IL-6 levels were 479.3 pg/ml and 934.5 pg/ml, respectively. The Candida burden showed significant correlation with serum IL-6 24 h p.i. (R2 = 0.6358; P = 0.0082) but not 72 h p.i.The second model was a mouse vaginitis model applying intravaginal inoculation of mice pretreated with subcutaneous estradiol-valerate (10 mg/ml) 3 days before infection. Candida cell count in vaginal lavage fluid was 2.8 × 106 CFU/ml 24 h p.i. and 1.4 × 108 CFU/ml 72 h p.i. Serum IL-6 response was detected in 4 of 15 mice 24 h p.i. and 9 of 15 mice 72 h p.i. Even the responders had low IL-6 serum levels (mean values 29.9 pg/ml and 60.1 pg/ml, respectively) not correlating with Candida cell count in vaginal lavage fluid.In conclusion, serum IL-6 had strong relationship with systemic C. albicans infection while the local C. albicans infection of the vagina led to partial, prolonged and limited serum IL-6 response.

Cross-reacting Material-positive Hemophilia A Diagnosed in a Patient with a Spontaneous Thigh Hemorrhage

PubMed Central

Saito, Tatsuya; Mukae, Jyunichi; Nakamura, Yosuke; Inaba, Hiroshi; Nogami, Keiji; Koyama, Takatoshi; Fukutake, Katsuyuki; Yamamoto, Koh

2017-01-01

A 53-year-old man, who had been diagnosed with mild hemophilia A (HA) at 35 years of age, was hospitalized with a thigh hematoma. His bleeding continued despite the administration of recombinant factor VIII (FVIII). The results of an FVIII/von Willebrand factor binding assay were normal. The patient's FVIII coagulant activity (FVIII:C) was low, but his FVIII antigen levels were within the normal limits, suggesting FVIII protein dysfunction. The FVIII:C measurements obtained by one-stage clotting and chromogenic assays were different. An FVIII gene analysis revealed a missense mutation p.Ser308Leu, which is rare in Japan. This case highlights that gene analyses and chromogenic assays are necessary to interpret the discrepancies between FVIII:C and the bleeding phenotype of patients with mild HA. PMID:28674365

Cross-reacting Material-positive Hemophilia A Diagnosed in a Patient with a Spontaneous Thigh Hemorrhage.

PubMed

Saito, Tatsuya; Mukae, Jyunichi; Nakamura, Yosuke; Inaba, Hiroshi; Nogami, Keiji; Koyama, Takatoshi; Fukutake, Katsuyuki; Yamamoto, Koh

2017-01-01

A 53-year-old man, who had been diagnosed with mild hemophilia A (HA) at 35 years of age, was hospitalized with a thigh hematoma. His bleeding continued despite the administration of recombinant factor VIII (FVIII). The results of an FVIII/von Willebrand factor binding assay were normal. The patient's FVIII coagulant activity (FVIII:C) was low, but his FVIII antigen levels were within the normal limits, suggesting FVIII protein dysfunction. The FVIII:C measurements obtained by one-stage clotting and chromogenic assays were different. An FVIII gene analysis revealed a missense mutation p.Ser308Leu, which is rare in Japan. This case highlights that gene analyses and chromogenic assays are necessary to interpret the discrepancies between FVIII:C and the bleeding phenotype of patients with mild HA.

Modeling risk of occupational zoonotic influenza infection in swine workers.

PubMed

Paccha, Blanca; Jones, Rachael M; Gibbs, Shawn; Kane, Michael J; Torremorell, Montserrat; Neira-Ramirez, Victor; Rabinowitz, Peter M

2016-08-01

Zoonotic transmission of influenza A virus (IAV) between swine and workers in swine production facilities may play a role in the emergence of novel influenza strains with pandemic potential. Guidelines to prevent transmission of influenza to swine workers have been developed but there is a need for evidence-based decision-making about protective measures such as respiratory protection. A mathematical model was applied to estimate the risk of occupational IAV exposure to swine workers by contact and airborne transmission, and to evaluate the use of respirators to reduce transmission.  The Markov model was used to simulate the transport and exposure of workers to IAV in a swine facility. A dose-response function was used to estimate the risk of infection. This approach is similar to methods previously used to estimate the risk of infection in human health care settings. This study uses concentration of virus in air from field measurements collected during outbreaks of influenza in commercial swine facilities, and analyzed by polymerase chain reaction.  It was found that spending 25 min working in a barn during an influenza outbreak in a swine herd could be sufficient to cause zoonotic infection in a worker. However, this risk estimate was sensitive to estimates of viral infectivity to humans. Wearing an excellent fitting N95 respirator reduced this risk, but with high aerosol levels the predicted risk of infection remained high under certain assumptions.  The results of this analysis indicate that under the conditions studied, swine workers are at risk of zoonotic influenza infection. The use of an N95 respirator could reduce such risk. These findings have implications for risk assessment and preventive programs targeting swine workers. The exact level of risk remains uncertain, since our model may have overestimated the viability or infectivity of IAV. Additionally, the potential for partial immunity in swine workers associated with repeated low

New Mouse Model for Chronic Infections by Gram-Negative Bacteria Enabling the Study of Anti-Infective Efficacy and Host-Microbe Interactions

PubMed Central

Pletzer, Daniel; Mansour, Sarah C.; Wuerth, Kelli; Rahanjam, Negin

2017-01-01

ABSTRACT Only a few, relatively cumbersome animal models enable long-term Gram-negative bacterial infections that mimic human situations, where untreated infections can last for weeks. Here, we describe a simple murine cutaneous abscess model that enables chronic or progressive infections, depending on the subcutaneously injected bacterial strain. In this model, Pseudomonas aeruginosa cystic fibrosis epidemic isolate LESB58 caused localized high-density skin and soft tissue infections and necrotic skin lesions for up to 10 days but did not disseminate in either CD-1 or C57BL/6 mice. The model was adapted for use with four major Gram-negative nosocomial pathogens, Acinetobacter baumannii, Klebsiella pneumoniae, Enterobacter cloacae, and Escherichia coli. This model enabled noninvasive imaging and tracking of lux-tagged bacteria, the influx of activated neutrophils, and production of reactive oxygen-nitrogen species at the infection site. Screening antimicrobials against high-density infections showed that local but not intravenous administration of gentamicin, ciprofloxacin, and meropenem significantly but incompletely reduced bacterial counts and superficial tissue dermonecrosis. Bacterial RNA isolated from the abscess tissue revealed that Pseudomonas genes involved in iron uptake, toxin production, surface lipopolysaccharide regulation, adherence, and lipase production were highly upregulated whereas phenazine production and expression of global activator gacA were downregulated. The model was validated for studying virulence using mutants of more-virulent P. aeruginosa strain PA14. Thus, mutants defective in flagella or motility, type III secretion, or siderophore biosynthesis were noninvasive and suppressed dermal necrosis in mice, while a strain with a mutation in the bfiS gene encoding a sensor kinase showed enhanced invasiveness and mortality in mice compared to controls infected with wild-type P. aeruginosa PA14. PMID:28246361

Inactivation of the CovR/S Virulence Regulator Impairs Infection in an Improved Murine Model of Streptococcus pyogenes Naso-Pharyngeal Infection

PubMed Central

Alam, Faraz M.; Turner, Claire E.; Smith, Ken; Wiles, Siouxsie; Sriskandan, Shiranee

2013-01-01

Streptococcus pyogenes is a leading cause of pharyngeal infection, with an estimated 616 million cases per year. The human nasopharynx represents the major reservoir for all S. pyogenes infection, including severe invasive disease. To investigate bacterial and host factors that influence S. pyogenes infection, we have devised an improved murine model of nasopharyngeal colonization, with an optimized dosing volume to avoid fulminant infections and a sensitive host strain. In addition we have utilized a refined technique for longitudinal monitoring of bacterial burden that is non-invasive thereby reducing the numbers of animals required. The model was used to demonstrate that the two component regulatory system, CovR/S, is required for optimum infection and transmission from the nasopharynx. There is a fitness cost conferred by covR/S mutation that is specific to the nasopharynx. This may explain why S. pyogenes with altered covR/S have not become prevalent in community infections despite possessing a selective advantage in invasive infection. PMID:23637876

[Identification of novel therapeutically effective antibiotics using silkworm infection model].

PubMed

Hamamoto, Hiroshi; Urai, Makoto; Paudel, Atmika; Horie, Ryo; Murakami, Kazuhisa; Sekimizu, Kazuhisa

2012-01-01

Most antibiotics obtained by in vitro screening with antibacterial activity have inappropriate properties as medicines due to their toxicity and pharmacodynamics in animal bodies. Thus, evaluation of the therapeutic effects of these samples using animal models is essential in the crude stage. Mammals are not suitable for therapeutic evaluation of a large number of samples due to high costs and ethical issues. We propose the use of silkworms (Bombyx mori) as model animals for screening therapeutically effective antibiotics. Silkworms are infected by various pathogenic bacteria and are effectively treated with similar ED(50) values of clinically used antibiotics. Furthermore, the drug metabolism pathways, such as cytochrome P450 and conjugation systems, are similar between silkworms and mammals. Silkworms have many advantages compared with other infection models, such as their 1) low cost, 2) few associated ethical problems, 3) adequate body size for easily handling, and 4) easier separation of organs and hemolymph. These features of the silkworm allow for efficient screening of therapeutically effective antibiotics. In this review, we discuss the advantages of the silkworm model in the early stages of drug development and the screening results of some antibiotics using the silkworm infection model.

The versatile use of revisited de-epithelialization concept in superficial circumflex iliac and anterolateral thigh perforator free flap for head and neck reconstructions.

PubMed

Choi, Jong Woo; Kim, Young Chul; Oh, Tae Suk; Koh, Kyung S; Jeong, Woo Shik

2017-06-01

Although the perforator free flap is now a standard choice for head and neck reconstruction, problems such as microvascular complications, insufficient volume support for the defect, and fistula formation occur. We revisited a de-epithelialized concept for superficial circumflex iliac artery and anterolateral thigh perforator free flap to overcome these problems. We applied the de-epithelized perforator free flaps in 35 cases among 761 microsurgical head and neck reconstructions and investigated flap characteristics (length gain of pedicle, flap size, and volumetric analysis) and outcomes (flap failure, partial flap necrosis, hematoma, infection, and fistula). Satisfactory results were achieved regarding flap survival, volumetric compensation, and fistula formation. Flaps were transferred successfully in all patients, although 1 patient underwent revisional operation due to venous congestion. Transferred flap volume was significantly higher than the resected tumor volume (p < 0.01), which suggests volume augmentation in the destroyed neck envelope and a protective role against adjuvant radiation. Minor dehiscence and bleeding were seen in two cases, and no other complications were identified. The de-epithelialization concept for perforator free flap is helpful to overcome obstacles related to traditional free flaps in terms of flap survival and volumetric augmentation in head and neck reconstructions. Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Modeling human influenza infection in the laboratory

PubMed Central

Radigan, Kathryn A; Misharin, Alexander V; Chi, Monica; Budinger, GR Scott

2015-01-01

Influenza is the leading cause of death from an infectious cause. Because of its clinical importance, many investigators use animal models to understand the biologic mechanisms of influenza A virus replication, the immune response to the virus, and the efficacy of novel therapies. This review will focus on the biosafety, biosecurity, and ethical concerns that must be considered in pursuing influenza research, in addition to focusing on the two animal models – mice and ferrets – most frequently used by researchers as models of human influenza infection. PMID:26357484

A mouse model of Salmonella typhi infection

PubMed Central

Mathur, Ramkumar; Oh, Hyunju; Zhang, Dekai; Park, Sung-Gyoo; Seo, Jin; Koblansky, Alicia; Hayden, Matthew S.; Ghosh, Sankar

2012-01-01

Salmonella spp. are gram-negative flagellated bacteria that can cause food and water-borne gastroenteritis and typhoid fever in humans. We now report that flagellin from Salmonella spp. is recognized in mouse intestine by Toll-like receptor 11 (TLR11). Absence of TLR11 renders mice more susceptible to infection by S. typhimurium, with increased dissemination of the bacteria and enhanced lethality. Unlike S. typhimurium, S. typhi, a human obligatory pathogen that causes typhoid fever, is normally unable to infect mice. TLR11 is expressed in mice but not in humans, and remarkably, we find that tlr11−/− mice are efficiently infected with orally-administered S. typhi. We also find that tlr11−/− mice can be immunized against S. typhi. Therefore, tlr11−/− mice represent the first small animal model for the study of the immune response to S. typhi, and for the development of vaccines against this important human pathogen. PMID:23101627

Chlamydial Pre-Infection Protects from Subsequent Herpes Simplex Virus-2 Challenge in a Murine Vaginal Super-Infection Model

PubMed Central

Slade, Jessica; Hall, Jennifer V.; Kintner, Jennifer; Schoborg, Robert V.

2016-01-01

Chlamydia trachomatis and Herpes Simplex Virus-2 (HSV-2) genital tract co-infections have been reported in humans and studied in vitro but the clinical consequences are unknown. Limited epidemiologic evidence suggests that these co-infections could be more severe than single infections of either pathogen, but the host-pathogen interactions during co-infection remain uncharacterized. To determine whether disease progression and/or pathogen shedding differs between singly-infected and super-infected animals, we developed an in vivo super-infection model in which female BALB/c mice were vaginally infected with Chlamydia muridarum (Cm) followed later by HSV-2. Pre-infection with Chlamydia 3 or 9 days prior to HSV-2 super-infection conferred significant protection from HSV-2-induced neurologic disease and significantly reduced viral recovery compared to HSV-2 singly-infected controls. Neither protection from mortality nor reduced viral recovery were observed when mice were i) super-infected with HSV-2 on day 27 post Cm; ii) infected with UV-irradiated Cm and super-infected with HSV-2; or iii) azithromycin-treated prior to HSV-2 super-infection. Therefore, protection from HSV-2-induced disease requires active infection with viable chlamydiae and is not observed after chlamydial shedding ceases, either naturally or due to antibiotic treatment. Thus, Chlamydia-induced protection is transient and requires the continued presence of chlamydiae or their components. These data demonstrate that chlamydial pre-infection can alter progression of subsequent HSV-2 infection, with implications for HSV-2 transmission from co-infected humans. PMID:26726882

Mathematical model for Dengue with three states of infection

NASA Astrophysics Data System (ADS)

Hincapie, Doracelly; Ospina, Juan

2012-06-01

A mathematical model for dengue with three states of infection is proposed and analyzed. The model consists in a system of differential equations. The three states of infection are respectively asymptomatic, partially asymptomatic and fully asymptomatic. The model is analyzed using computer algebra software, specifically Maple, and the corresponding basic reproductive number and the epidemic threshold are computed. The resulting basic reproductive number is an algebraic synthesis of all epidemic parameters and it makes clear the possible control measures. The microscopic structure of the epidemic parameters is established using the quantum theory of the interactions between the atoms and radiation. In such approximation, the human individual is represented by an atom and the mosquitoes are represented by radiation. The force of infection from the mosquitoes to the humans is considered as the transition probability from the fundamental state of atom to excited states. The combination of computer algebra software and quantum theory provides a very complete formula for the basic reproductive number and the possible control measures tending to stop the propagation of the disease. It is claimed that such result may be important in military medicine and the proposed method can be applied to other vector-borne diseases.

Bilayered negative-pressure wound therapy preventing leg incision morbidity in coronary artery bypass graft patients

PubMed Central

Yu, Yongchao; Song, Zhigang; Xu, Zhiyun; Ye, Xiaofei; Xue, Chunyu; Li, Junhui; Bi, Hongda

2017-01-01

Abstract Backgrounds: The harvesting of great saphenous veins for coronary artery bypass graft (CABG) patients may result in significant complications, including lymphorrhagia, lymphoedema, incision infection, wound dehiscence, and skin flap necrosis. We investigated the function of a self-designed bilayered negative pressure wound therapy (b-NPWT) for reducing the above-mentioned complications using a clinical randomized controlled trial. Methods: A single-center, pilot randomized controlled trial was conducted. From December 2013 to March 2014, a total of 72 coronary heart disease patients (48 men and 24 women) received CABG therapy, with great saphenous veins were selected as grafts. Patients were equally randomized into a treatment and a control group. After the harvesting of the great saphenous veins and direct closure of the wound with sutures, b-NPWT was used for the thigh incision in the treatment group for 5 days (treatment thigh). Traditional surgical pads were applied to both the shank incisions of the treatment group patients (treatment shank) and the entire incisions of the control group (control thigh, control shank). Postoperative complications were recorded and statistically analyzed based on outcomes of thigh treatment, shank treatment, thigh control, and shank control groups. Results: The incidence rates of early complications, such as lymphorrhagia, lymphoedema, infection, wound dehiscence, and skin flap necrosis, of the vascular donor site in the thigh treatment group was significantly lower than those in the 3 other groups. Conclusions: The self-designed b-NPWT can effectively reduce postoperative complications, such as lymphedema, incision infection, wound dehiscence, and skin flap necrosis, in CABG patients who underwent great saphenous veins harvesting. Trial registration: ClinicalTrials.gov. The unique registration number is NCT02010996. PMID:28099357

Modeling Dental Health Care Workers' Risk of Occupational Infection from Bloodborne Pathogens.

ERIC Educational Resources Information Center

Capilouto, Eli; And Others

1990-01-01

The brief paper offers a model which permits quantification of the dental health care workers' risk of occupationally acquiring infection from bloodborne pathogens such as human immunodeficiency virus and hepatitis B virus. The model incorporates five parameters such as the probability that any individual patient is infected and number of patients…

Exploring the benefits of antibody immune response in HIV-1 infection using a discrete model.

PubMed

Showa, S P; Nyabadza, F; Hove-Musekwa, S D; Magombedze, G

2016-06-01

The role of antibodies in HIV-1 infection is investigated using a discrete-time mathematical model that considers cell-free and cell-associated transmission of the virus. Model analysis shows that the effect of each type of antibody is dependent on the stage of the infection. Neutralizing antibodies are efficient in controlling the viral levels in the early days after seroconversion and antibodies that coat HIV-1-infected cells and recruit effector cells to either kill the HIV-1-infected cells or inhibit viral replication are efficient when the infection becomes established. Model simulations show that antibodies that inhibit viral replication are more effective in controlling the infection than those that recruit Natural Killer T cells after infection establishment. The model was fitted to subjects of the Tsedimoso study conducted in Botswana and conclusions similar to elasticity analysis results were obtained. Model fitting results predicted that neutralizing antibodies are more efficient in controlling the viral levels than antibodies that coat HIV-1-infected cells and recruit effector cells to either kill the HIV-1-infected cells or inhibit viral replication in the early days after seroconversion. © The Authors 2015. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.

Effect of supplemental fermented Ginkgo biloba leaves at different levels on growth performance, meat quality, and antioxidant status of breast and thigh muscles in broiler chickens.

PubMed

Niu, Y; Wan, X L; Zhang, X H; Zhao, L G; He, J T; Zhang, J F; Zhang, L L; Wang, T

2017-04-01

The present study was conducted to investigate the influence of dietary supplementation with different levels of fermented Ginkgo biloba leaves (FGBL) on growth performance, slaughter performance, meat quality, antioxidant enzyme capacity, and free radical scavenging activities of muscles in broiler chickens. A total of 648 one-d-old broiler chickens were randomly allocated into six dietary treatments, including control group (CON group: basal diet), FGBL1, FGBL2, FGBL3, FGBL4, and FGBL5 groups (basal diet containing 1.5, 2.5, 3.5, 4.5, and 5.5 g/kg FGBL, respectively). Body weight gain and feed intake were recorded at 1, 21, and 42 d. At 42 d, 2 birds from each replicate were slaughtered. The results indicated that 3.5 g/kg FGBL diet significantly increased (P < 0.05) ADFI and ADG in 1 to 42 d and ADFI in 22 to 42 d compared with the CON group. In 1 to 21 d, 4.5 g/kg FGBL diet improved (P < 0.05) ADFI and ADG. With dietary FGBL increasing, the feed: gain ratio (F/G) in 1 to 21 d was significantly decreased (P < 0.05). However, birds fed with 5.5 g/kg FGBL had a higher (P < 0.05) F/G compared with other groups in 22 to 42 d and 1 to 42 d. In addition, FGBL3 and FGBL4 showed lower (P < 0.05) L* value in breast muscle, cooking loss in thigh muscle and lower 24 h and 48 h drip loss in both breast and thigh muscles than those of other groups. Furthermore, birds in the FGBL3 and FGBL4 groups increased (P < 0.05) the activity of total superoxide dismutase and total antioxidant capability in muscles, and the scavenging activities of 2,2΄-azino-bis (3-ethylbenzothiazoline-6-sulfonic) acid radical, OH•, and O2•- in thigh muscle, decreased (P < 0.05) malondialdehyde concentration in thigh muscle, as compared to the CON group. In conclusion, FGBL had the potential to improve the growth performance, meat quality and antioxidant status of broiler chickens. The optimal dose in the present study of FGBL in broiler diets was from 3.5 to 4.5 g/kg. © 2016

Using experimental human influenza infections to validate a viral dynamic model and the implications for prediction.

PubMed

Chen, S C; You, S H; Liu, C Y; Chio, C P; Liao, C M

2012-09-01

The aim of this work was to use experimental infection data of human influenza to assess a simple viral dynamics model in epithelial cells and better understand the underlying complex factors governing the infection process. The developed study model expands on previous reports of a target cell-limited model with delayed virus production. Data from 10 published experimental infection studies of human influenza was used to validate the model. Our results elucidate, mechanistically, the associations between epithelial cells, human immune responses, and viral titres and were supported by the experimental infection data. We report that the maximum total number of free virions following infection is 10(3)-fold higher than the initial introduced titre. Our results indicated that the infection rates of unprotected epithelial cells probably play an important role in affecting viral dynamics. By simulating an advanced model of viral dynamics and applying it to experimental infection data of human influenza, we obtained important estimates of the infection rate. This work provides epidemiologically meaningful results, meriting further efforts to understand the causes and consequences of influenza A infection.

A Novel Highly Reproducible and Lethal Nonhuman Primate Model for Orthopox Virus Infection

PubMed Central

Kramski, Marit; Mätz-Rensing, Kerstin; Stahl-Hennig, Christiane; Kaup, Franz-Josef; Nitsche, Andreas; Pauli, Georg; Ellerbrok, Heinz

2010-01-01

The intentional re-introduction of Variola virus (VARV), the agent of smallpox, into the human population is of great concern due its bio-terroristic potential. Moreover, zoonotic infections with Cowpox (CPXV) and Monkeypox virus (MPXV) cause severe diseases in humans. Smallpox vaccines presently available can have severe adverse effects that are no longer acceptable. The efficacy and safety of new vaccines and antiviral drugs for use in humans can only be demonstrated in animal models. The existing nonhuman primate models, using VARV and MPXV, need very high viral doses that have to be applied intravenously or intratracheally to induce a lethal infection in macaques. To overcome these drawbacks, the infectivity and pathogenicity of a particular CPXV was evaluated in the common marmoset (Callithrix jacchus). A CPXV named calpox virus was isolated from a lethal orthopox virus (OPV) outbreak in New World monkeys. We demonstrated that marmosets infected with calpox virus, not only via the intravenous but also the intranasal route, reproducibly develop symptoms resembling smallpox in humans. Infected animals died within 1–3 days after onset of symptoms, even when very low infectious viral doses of 5×102 pfu were applied intranasally. Infectious virus was demonstrated in blood, saliva and all organs analyzed. We present the first characterization of a new OPV infection model inducing a disease in common marmosets comparable to smallpox in humans. Intranasal virus inoculation mimicking the natural route of smallpox infection led to reproducible infection. In vivo titration resulted in an MID50 (minimal monkey infectious dose 50%) of 8.3×102 pfu of calpox virus which is approximately 10,000-fold lower than MPXV and VARV doses applied in the macaque models. Therefore, the calpox virus/marmoset model is a suitable nonhuman primate model for the validation of vaccines and antiviral drugs. Furthermore, this model can help study mechanisms of OPV pathogenesis. PMID

An age-structured model of hiv infection that allows for variations in the production rate of viral particles and the death rate of productively infected cells.

PubMed

Nelson, Patrick W; Gilchrist, Michael A; Coombs, Daniel; Hyman, James M; Perelson, Alan S

2004-09-01

Mathematical models of HIV-1 infection can help interpret drug treatment experiments and improve our understanding of the interplay between HIV-1 and the immune system. We develop and analyze an age- structured model of HIV-1 infection that allows for variations in the death rate of productively infected T cells and the production rate of viral particles as a function of the length of time a T cell has been infected. We show that this model is a generalization of the standard differential equation and of delay models previously used to describe HIV-1 infection, and provides a means for exploring fundamental issues of viral production and death. We show that the model has uninfected and infected steady states, linked by a transcritical bifurcation. We perform a local stability analysis of the nontrivial equilibrium solution and provide a general stability condition for models with age structure. We then use numerical methods to study solutions of our model focusing on the analysis of primary HIV infection. We show that the time to reach peak viral levels in the blood depends not only on initial conditions but also on the way in which viral production ramps up. If viral production ramps up slowly, we find that the time to peak viral load is delayed compared to results obtained using the standard (constant viral production) model of HIV infection. We find that data on viral load changing over time is insufficient to identify the functions specifying the dependence of the viral production rate or infected cell death rate on infected cell age. These functions must be determined through new quantitative experiments.

Stability Analysis Susceptible, Exposed, Infected, Recovered (SEIR) Model for Spread Model for Spread of Dengue Fever in Medan

NASA Astrophysics Data System (ADS)

Side, Syafruddin; Molliq Rangkuti, Yulita; Gerhana Pane, Dian; Setia Sinaga, Marlina

2018-01-01

Dengue fever is endemic disease which spread through vector, Aedes Aegypty. This disease is found more than 100 countries, such as, United State, Africa as well Asia, especially in country that have tropic climate. Mathematical modeling in this paper, discusses the speed of the spread of dengue fever. The model adopting divided over four classes, such as Susceptible (S), Exposed (E), Infected (I) and Recovered (R). SEIR model further analyzed to detect the re-breeding value based on the number reported case by dengue in Medan city. Analysis of the stability of the system in this study is asymptotically stable indicating a case of endemic and unstable that show cases the endemic cases. Simulation on the mathematical model of SEIR showed that require a very long time to produce infected humans will be free of dengue virus infection. This happens because of dengue virus infection that occurs continuously between human and vector populations.

The Impact of Chocolate Goat's and Cow's Milk on Postresistance Exercise Endocrine Responses and Isometric Mid-Thigh Pull Performance.

PubMed

Bellar, David; LeBlanc, Nina R; Murphy, Kellie; Moody, Kaitlyn M; Buquet, Gina

2016-01-01

The present investigation examined the effects of chocolate cow's and goat's milk on endocrine responses and isometric mid-thigh pull performance post back squat exercise. Twelve college-aged males volunteered to participate and reported to the lab on four occasions. The first visit included anthropometric measurement, one-repetition back squat (1RM), and familiarization with the isometric mid-thigh pull assessment (IMTP). During the subsequent three visits, five sets of eight repetitions of the back squat exercise at 80% of 1RM were performed. For these trials, the participants performed an IMTP and gave a saliva sample prior to, immediately after, 1 hr and 2 hr post exercise. After exercise, a treatment of low-fat chocolate goat's milk (355 ml, 225 kcal), low-fat chocolate cow's milk (355 ml, 225 kcal), or control (water 355 ml, 0 kcal) was given in a counterbalanced order. Saliva samples were analyzed for testosterone, cortisol, and dehydroepiandrosterone (DHEA). Cortisol and DHEA hormone were unaffected by exercise; however, testosterone values did increase significantly post exercise. For IMTP, there was a significant main effect for time (F = 8.41, p = .007) but no treatment or interactions effects. N changes were noted post supplementation for cortisol or DHEA, but testosterone was found to be significantly reduced in both diary treatments compared to control (F = 4.27, p = .022). Based upon these data, it appears that a single treatment of chocolate goat's or cow's milk results in similar endocrine alterations but both fail to enhance postexercise isometric strength following resistance exercise.

Thigh muscle segmentation of chemical shift encoding-based water-fat magnetic resonance images: The reference database MyoSegmenTUM.

PubMed

Schlaeger, Sarah; Freitag, Friedemann; Klupp, Elisabeth; Dieckmeyer, Michael; Weidlich, Dominik; Inhuber, Stephanie; Deschauer, Marcus; Schoser, Benedikt; Bublitz, Sarah; Montagnese, Federica; Zimmer, Claus; Rummeny, Ernst J; Karampinos, Dimitrios C; Kirschke, Jan S; Baum, Thomas

2018-01-01

Magnetic resonance imaging (MRI) can non-invasively assess muscle anatomy, exercise effects and pathologies with different underlying causes such as neuromuscular diseases (NMD). Quantitative MRI including fat fraction mapping using chemical shift encoding-based water-fat MRI has emerged for reliable determination of muscle volume and fat composition. The data analysis of water-fat images requires segmentation of the different muscles which has been mainly performed manually in the past and is a very time consuming process, currently limiting the clinical applicability. An automatization of the segmentation process would lead to a more time-efficient analysis. In the present work, the manually segmented thigh magnetic resonance imaging database MyoSegmenTUM is presented. It hosts water-fat MR images of both thighs of 15 healthy subjects and 4 patients with NMD with a voxel size of 3.2x2x4 mm3 with the corresponding segmentation masks for four functional muscle groups: quadriceps femoris, sartorius, gracilis, hamstrings. The database is freely accessible online at https://osf.io/svwa7/?view_only=c2c980c17b3a40fca35d088a3cdd83e2. The database is mainly meant as ground truth which can be used as training and test dataset for automatic muscle segmentation algorithms. The segmentation allows extraction of muscle cross sectional area (CSA) and volume. Proton density fat fraction (PDFF) of the defined muscle groups from the corresponding images and quadriceps muscle strength measurements/neurological muscle strength rating can be used for benchmarking purposes.

Effects of infection on honey bee population dynamics: a model.

PubMed

Betti, Matt I; Wahl, Lindi M; Zamir, Mair

2014-01-01

We propose a model that combines the dynamics of the spread of disease within a bee colony with the underlying demographic dynamics of the colony to determine the ultimate fate of the colony under different scenarios. The model suggests that key factors in the survival or collapse of a honey bee colony in the face of an infection are the rate of transmission of the infection and the disease-induced death rate. An increase in the disease-induced death rate, which can be thought of as an increase in the severity of the disease, may actually help the colony overcome the disease and survive through winter. By contrast, an increase in the transmission rate, which means that bees are being infected at an earlier age, has a drastic deleterious effect. Another important finding relates to the timing of infection in relation to the onset of winter, indicating that in a time interval of approximately 20 days before the onset of winter the colony is most affected by the onset of infection. The results suggest further that the age of recruitment of hive bees to foraging duties is a good early marker for the survival or collapse of a honey bee colony in the face of infection, which is consistent with experimental evidence but the model provides insight into the underlying mechanisms. The most important result of the study is a clear distinction between an exposure of the honey bee colony to an environmental hazard such as pesticides or insecticides, or an exposure to an infectious disease. The results indicate unequivocally that in the scenarios that we have examined, and perhaps more generally, an infectious disease is far more hazardous to the survival of a bee colony than an environmental hazard that causes an equal death rate in foraging bees.

Effects of Infection on Honey Bee Population Dynamics: A Model

PubMed Central

Betti, Matt I.; Wahl, Lindi M.; Zamir, Mair

2014-01-01

We propose a model that combines the dynamics of the spread of disease within a bee colony with the underlying demographic dynamics of the colony to determine the ultimate fate of the colony under different scenarios. The model suggests that key factors in the survival or collapse of a honey bee colony in the face of an infection are the rate of transmission of the infection and the disease-induced death rate. An increase in the disease-induced death rate, which can be thought of as an increase in the severity of the disease, may actually help the colony overcome the disease and survive through winter. By contrast, an increase in the transmission rate, which means that bees are being infected at an earlier age, has a drastic deleterious effect. Another important finding relates to the timing of infection in relation to the onset of winter, indicating that in a time interval of approximately 20 days before the onset of winter the colony is most affected by the onset of infection. The results suggest further that the age of recruitment of hive bees to foraging duties is a good early marker for the survival or collapse of a honey bee colony in the face of infection, which is consistent with experimental evidence but the model provides insight into the underlying mechanisms. The most important result of the study is a clear distinction between an exposure of the honey bee colony to an environmental hazard such as pesticides or insecticides, or an exposure to an infectious disease. The results indicate unequivocally that in the scenarios that we have examined, and perhaps more generally, an infectious disease is far more hazardous to the survival of a bee colony than an environmental hazard that causes an equal death rate in foraging bees. PMID:25329468

Modeling two strains of disease via aggregate-level infectivity curves.

PubMed

Romanescu, Razvan; Deardon, Rob

2016-04-01

Well formulated models of disease spread, and efficient methods to fit them to observed data, are powerful tools for aiding the surveillance and control of infectious diseases. Our project considers the problem of the simultaneous spread of two related strains of disease in a context where spatial location is the key driver of disease spread. We start our modeling work with the individual level models (ILMs) of disease transmission, and extend these models to accommodate the competing spread of the pathogens in a two-tier hierarchical population (whose levels we refer to as 'farm' and 'animal'). The postulated interference mechanism between the two strains is a period of cross-immunity following infection. We also present a framework for speeding up the computationally intensive process of fitting the ILM to data, typically done using Markov chain Monte Carlo (MCMC) in a Bayesian framework, by turning the inference into a two-stage process. First, we approximate the number of animals infected on a farm over time by infectivity curves. These curves are fit to data sampled from farms, using maximum likelihood estimation, then, conditional on the fitted curves, Bayesian MCMC inference proceeds for the remaining parameters. Finally, we use posterior predictive distributions of salient epidemic summary statistics, in order to assess the model fitted.

The challenges of modelling antibody repertoire dynamics in HIV infection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luo, Shishi; Perelson, Alan S.

Antibody affinity maturation by somatic hypermutation of B-cell immunoglobulin variable region genes has been studied for decades in various model systems using well-defined antigens. While much is known about the molecular details of the process, our understanding of the selective forces that generate affinity maturation are less well developed, particularly in the case of a co-evolving pathogen such as HIV. Despite this gap in understanding, high-throughput antibody sequence data are increasingly being collected to investigate the evolutionary trajectories of antibody lineages in HIV-infected individuals. Here, we review what is known in controlled experimental systems about the mechanisms underlying antibody selectionmore » and compare this to the observed temporal patterns of antibody evolution in HIV infection. In addition, we describe how our current understanding of antibody selection mechanisms leaves questions about antibody dynamics in HIV infection unanswered. Without a mechanistic understanding of antibody selection in the context of a co-evolving viral population, modelling and analysis of antibody sequences in HIV-infected individuals will be limited in their interpretation and predictive ability.« less

The challenges of modelling antibody repertoire dynamics in HIV infection

DOE PAGES

Luo, Shishi; Perelson, Alan S.

2015-07-20

Antibody affinity maturation by somatic hypermutation of B-cell immunoglobulin variable region genes has been studied for decades in various model systems using well-defined antigens. While much is known about the molecular details of the process, our understanding of the selective forces that generate affinity maturation are less well developed, particularly in the case of a co-evolving pathogen such as HIV. Despite this gap in understanding, high-throughput antibody sequence data are increasingly being collected to investigate the evolutionary trajectories of antibody lineages in HIV-infected individuals. Here, we review what is known in controlled experimental systems about the mechanisms underlying antibody selectionmore » and compare this to the observed temporal patterns of antibody evolution in HIV infection. In addition, we describe how our current understanding of antibody selection mechanisms leaves questions about antibody dynamics in HIV infection unanswered. Without a mechanistic understanding of antibody selection in the context of a co-evolving viral population, modelling and analysis of antibody sequences in HIV-infected individuals will be limited in their interpretation and predictive ability.« less

A human lung xenograft mouse model of Nipah virus infection.

PubMed

Valbuena, Gustavo; Halliday, Hailey; Borisevich, Viktoriya; Goez, Yenny; Rockx, Barry

2014-04-01

Nipah virus (NiV) is a member of the genus Henipavirus (family Paramyxoviridae) that causes severe and often lethal respiratory illness and encephalitis in humans with high mortality rates (up to 92%). NiV can cause Acute Lung Injury (ALI) in humans, and human-to-human transmission has been observed in recent outbreaks of NiV. While the exact route of transmission to humans is not known, we have previously shown that NiV can efficiently infect human respiratory epithelial cells. The molecular mechanisms of NiV-associated ALI in the human respiratory tract are unknown. Thus, there is an urgent need for models of henipavirus infection of the human respiratory tract to study the pathogenesis and understand the host responses. Here, we describe a novel human lung xenograft model in mice to study the pathogenesis of NiV. Following transplantation, human fetal lung xenografts rapidly graft and develop mature structures of adult lungs including cartilage, vascular vessels, ciliated pseudostratified columnar epithelium, and primitive "air" spaces filled with mucus and lined by cuboidal to flat epithelium. Following infection, NiV grows to high titers (10(7) TCID50/gram lung tissue) as early as 3 days post infection (pi). NiV targets both the endothelium as well as respiratory epithelium in the human lung tissues, and results in syncytia formation. NiV infection in the human lung results in the production of several cytokines and chemokines including IL-6, IP-10, eotaxin, G-CSF and GM-CSF on days 5 and 7 pi. In conclusion, this study demonstrates that NiV can replicate to high titers in a novel in vivo model of the human respiratory tract, resulting in a robust inflammatory response, which is known to be associated with ALI. This model will facilitate progress in the fundamental understanding of henipavirus pathogenesis and virus-host interactions; it will also provide biologically relevant models for other respiratory viruses.

Predictive Virtual Infection Modeling of Fungal Immune Evasion in Human Whole Blood.

PubMed

Prauße, Maria T E; Lehnert, Teresa; Timme, Sandra; Hünniger, Kerstin; Leonhardt, Ines; Kurzai, Oliver; Figge, Marc Thilo

2018-01-01

Bloodstream infections by the human-pathogenic fungi Candida albicans and Candida glabrata increasingly occur in hospitalized patients and are associated with high mortality rates. The early immune response against these fungi in human blood comprises a concerted action of humoral and cellular components of the innate immune system. Upon entering the blood, the majority of fungal cells will be eliminated by innate immune cells, i.e., neutrophils and monocytes. However, recent studies identified a population of fungal cells that can evade the immune response and thereby may disseminate and cause organ dissemination, which is frequently observed during candidemia. In this study, we investigate the so far unresolved mechanism of fungal immune evasion in human whole blood by testing hypotheses with the help of mathematical modeling. We use a previously established state-based virtual infection model for whole-blood infection with C. albicans to quantify the immune response and identified the fungal immune-evasion mechanism. While this process was assumed to be spontaneous in the previous model, we now hypothesize that the immune-evasion process is mediated by host factors and incorporate such a mechanism in the model. In particular, we propose, based on previous studies that the fungal immune-evasion mechanism could possibly arise through modification of the fungal surface by as of yet unknown proteins that are assumed to be secreted by activated neutrophils. To validate or reject any of the immune-evasion mechanisms, we compared the simulation of both immune-evasion models for different infection scenarios, i.e., infection of whole blood with either C. albicans or C. glabrata under non-neutropenic and neutropenic conditions. We found that under non-neutropenic conditions, both immune-evasion models fit the experimental data from whole-blood infection with C. albicans and C. glabrata . However, differences between the immune-evasion models could be observed for the

Predictive Virtual Infection Modeling of Fungal Immune Evasion in Human Whole Blood

PubMed Central

Prauße, Maria T. E.; Lehnert, Teresa; Timme, Sandra; Hünniger, Kerstin; Leonhardt, Ines; Kurzai, Oliver; Figge, Marc Thilo

2018-01-01

Bloodstream infections by the human-pathogenic fungi Candida albicans and Candida glabrata increasingly occur in hospitalized patients and are associated with high mortality rates. The early immune response against these fungi in human blood comprises a concerted action of humoral and cellular components of the innate immune system. Upon entering the blood, the majority of fungal cells will be eliminated by innate immune cells, i.e., neutrophils and monocytes. However, recent studies identified a population of fungal cells that can evade the immune response and thereby may disseminate and cause organ dissemination, which is frequently observed during candidemia. In this study, we investigate the so far unresolved mechanism of fungal immune evasion in human whole blood by testing hypotheses with the help of mathematical modeling. We use a previously established state-based virtual infection model for whole-blood infection with C. albicans to quantify the immune response and identified the fungal immune-evasion mechanism. While this process was assumed to be spontaneous in the previous model, we now hypothesize that the immune-evasion process is mediated by host factors and incorporate such a mechanism in the model. In particular, we propose, based on previous studies that the fungal immune-evasion mechanism could possibly arise through modification of the fungal surface by as of yet unknown proteins that are assumed to be secreted by activated neutrophils. To validate or reject any of the immune-evasion mechanisms, we compared the simulation of both immune-evasion models for different infection scenarios, i.e., infection of whole blood with either C. albicans or C. glabrata under non-neutropenic and neutropenic conditions. We found that under non-neutropenic conditions, both immune-evasion models fit the experimental data from whole-blood infection with C. albicans and C. glabrata. However, differences between the immune-evasion models could be observed for the

Reconstruction of Anterolateral Thigh Defects Using Perforator-Based Propeller Flaps.

PubMed

Iida, Takuya; Yoshimatsu, Hidehiko; Koshima, Isao

2017-10-01

Usually, anterolateral thigh (ALT) defects with width more than 8 cm cannot be closed directly. Although several methods of using local flaps exist, flap mobility of these methods is limited. We introduced a perforator-based propeller flap for such reconstruction. Their maximal mobility, which minimizes their size, is their greatest advantage. In addition, we present our technical refinements including double-axes propeller flap, the use of indocyanine green real-time angiography, and supercharged propeller flap for safer flap transfer. Seven patients underwent perforator-based propeller flap reconstruction of ALT defects. Flaps were designed cranial or caudal to the defect according to the perforator locations. To maximize mobility, flaps were designed so that the perforator was located at the periphery and closer to the defect. After rotating the flap to the defect, indocyanine green angiography was performed to determine the need for supercharge. In all cases, all flaps survived completely. Defect size ranged from 12 × 11 cm to 18 × 16 cm, and flap size ranged from 7 × 5 cm to 15 × 7 cm. The number of perforators in the flap was 1 in 3 cases and 2 in 4 cases. Supercharging was performed in 3 cases. Donor-site complications, including gait disturbance, were not observed. This method achieves ALT defect closure with minimal donor-site morbidity and can provide prompt and aesthetically acceptable results. Indocyanine green real-time angiography and supercharging technique are also useful for safer and reliable flap transfer.

Epidemic models with an infected-infectious period

NASA Astrophysics Data System (ADS)

Méndez, Vicenç

1998-03-01

The introduction of an infective-infectious period on the geographic spread of epidemics is considered in two different models. The classical evolution equations arising in the literature are generalized and the existence of epidemic wave fronts is revised. The asymptotic speed is obtained and improves previous results for the Black Death plague.

Large-scale maps of variable infection efficiencies in aquatic Bacteroidetes phage-host model systems: Variable phage-host infection interactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holmfeldt, Karin; Solonenko, Natalie; Howard-Varona, Cristina

Microbes drive ecosystem functioning and their viruses modulate these impacts through mortality, gene transfer and metabolic reprogramming. Despite the importance of virus-host interactions and likely variable infection efficiencies of individual phages across hosts, such variability is seldom quantified. In this paper, we quantify infection efficiencies of 38 phages against 19 host strains in aquatic Cellulophaga (Bacteroidetes) phage-host model systems. Binary data revealed that some phages infected only one strain while others infected 17, whereas quantitative data revealed that efficiency of infection could vary 10 orders of magnitude, even among phages within one population. This provides a baseline for understanding andmore » modeling intrapopulation host range variation. Genera specific host ranges were also informative. For example, the Cellulophaga Microviridae, showed a markedly broader intra-species host range than previously observed in Escherichia coli systems. Further, one phage genus, Cba41, was examined to investigate nonheritable changes in plating efficiency and burst size that depended on which host strain it most recently infected. While consistent with host modification of phage DNA, no differences in nucleotide sequence or DNA modifications were detected, leaving the observation repeatable, but the mechanism unresolved. Overall, this study highlights the importance of quantitatively considering replication variations in studies of phage-host interactions.« less

Large-scale maps of variable infection efficiencies in aquatic Bacteroidetes phage-host model systems: Variable phage-host infection interactions

DOE PAGES

Holmfeldt, Karin; Solonenko, Natalie; Howard-Varona, Cristina; ...

2016-06-28

Microbes drive ecosystem functioning and their viruses modulate these impacts through mortality, gene transfer and metabolic reprogramming. Despite the importance of virus-host interactions and likely variable infection efficiencies of individual phages across hosts, such variability is seldom quantified. In this paper, we quantify infection efficiencies of 38 phages against 19 host strains in aquatic Cellulophaga (Bacteroidetes) phage-host model systems. Binary data revealed that some phages infected only one strain while others infected 17, whereas quantitative data revealed that efficiency of infection could vary 10 orders of magnitude, even among phages within one population. This provides a baseline for understanding andmore » modeling intrapopulation host range variation. Genera specific host ranges were also informative. For example, the Cellulophaga Microviridae, showed a markedly broader intra-species host range than previously observed in Escherichia coli systems. Further, one phage genus, Cba41, was examined to investigate nonheritable changes in plating efficiency and burst size that depended on which host strain it most recently infected. While consistent with host modification of phage DNA, no differences in nucleotide sequence or DNA modifications were detected, leaving the observation repeatable, but the mechanism unresolved. Overall, this study highlights the importance of quantitatively considering replication variations in studies of phage-host interactions.« less

Longitudinal Modeling of Depressive Trajectories Among HIV-Infected Men Using Cocaine.

PubMed

Mukerji, Shibani; Haghighat, Roxanna; Misra, Vikas; Lorenz, David R; Holman, Alex; Dutta, Anupriya; Gabuzda, Dana

2017-07-01

Cocaine use is prevalent among HIV-infected individuals. While cross-sectional studies suggest that cocaine users may be at increased risk for depression, long-term effects of cocaine on depressive symptoms remain unclear. This is a longitudinal study of 341 HIV-infected and uninfected men (135 cocaine users and 206 controls) ages 30-60 enrolled in the Multicenter AIDS Cohort Study during 1996-2009. The median baseline age was 41; 73% were African-American. In mixed-effects models over a median of 4.8 years of observation, cocaine use was associated with higher depressive symptoms independent of age, education level, and smoking (n = 288; p = 0.02); HIV infection modified this association (p = 0.03). Latent class mixed models were used to empirically identify distinct depressive trajectories (n = 160). In adjusted models, cocaine use was associated with threefold increased odds of membership in the class with persistent high depressive symptoms (95% confidence interval (CI) 1.38-6.69) and eightfold increased odds (95% CI (2.73-25.83) when tested among HIV-infected subjects only. Cocaine use is a risk factor for chronic depressive symptoms, particularly among HIV-infected men, highlighting the importance of integrating mental health and substance use treatments to address barriers to well-being and successful HIV-care.

Non-invasive model of neuropathogenic Escherichia coli infection in the neonatal rat.

PubMed

Dalgakiran, Fatma; Witcomb, Luci A; McCarthy, Alex J; Birchenough, George M H; Taylor, Peter W

2014-10-29

Investigation of the interactions between animal host and bacterial pathogen is only meaningful if the infection model employed replicates the principal features of the natural infection. This protocol describes procedures for the establishment and evaluation of systemic infection due to neuropathogenic Escherichia coli K1 in the neonatal rat. Colonization of the gastrointestinal tract leads to dissemination of the pathogen along the gut-lymph-blood-brain course of infection and the model displays strong age dependency. A strain of E. coli O18:K1 with enhanced virulence for the neonatal rat produces exceptionally high rates of colonization, translocation to the blood compartment and invasion of the meninges following transit through the choroid plexus. As in the human host, penetration of the central nervous system is accompanied by local inflammation and an invariably lethal outcome. The model is of proven utility for studies of the mechanism of pathogenesis, for evaluation of therapeutic interventions and for assessment of bacterial virulence.

Applications of physiologically based pharmacokinetic modeling for the optimization of anti-infective therapies.

PubMed

Moss, Darren Michael; Marzolini, Catia; Rajoli, Rajith K R; Siccardi, Marco

2015-01-01

The pharmacokinetic properties of anti-infective drugs are a determinant part of treatment success. Pathogen replication is inhibited if adequate drug levels are achieved in target sites, whereas excessive drug concentrations linked to toxicity are to be avoided. Anti-infective distribution can be predicted by integrating in vitro drug properties and mathematical descriptions of human anatomy in physiologically based pharmacokinetic models. This method reduces the need for animal and human studies and is used increasingly in drug development and simulation of clinical scenario such as, for instance, drug-drug interactions, dose optimization, novel formulations and pharmacokinetics in special populations. We have assessed the relevance of physiologically based pharmacokinetic modeling in the anti-infective research field, giving an overview of mechanisms involved in model design and have suggested strategies for future applications of physiologically based pharmacokinetic models. Physiologically based pharmacokinetic modeling provides a powerful tool in anti-infective optimization, and there is now no doubt that both industry and regulatory bodies have recognized the importance of this technology. It should be acknowledged, however, that major challenges remain to be addressed and that information detailing disease group physiology and anti-infective pharmacodynamics is required if a personalized medicine approach is to be achieved.

Rat Indwelling Urinary Catheter Model of Candida albicans Biofilm Infection

PubMed Central

Nett, Jeniel E.; Brooks, Erin G.; Cabezas-Olcoz, Jonathan; Sanchez, Hiram; Zarnowski, Robert; Marchillo, Karen

2014-01-01

Indwelling urinary catheters are commonly used in the management of hospitalized patients. Candida can adhere to the device surface and propagate as a biofilm. These Candida biofilm communities differ from free-floating Candida, exhibiting high tolerance to antifungal therapy. The significance of catheter-associated candiduria is often unclear, and treatment may be problematic considering the biofilm drug-resistant phenotype. Here we describe a rodent model for the study of urinary catheter-associated Candida albicans biofilm infection that mimics this common process in patients. In the setting of a functioning, indwelling urinary catheter in a rat, Candida proliferated as a biofilm on the device surface. Characteristic biofilm architecture was observed, including adherent, filamentous cells embedded in an extracellular matrix. Similar to what occurs in human patients, animals with this infection developed candiduria and pyuria. Infection progressed to cystitis, and a biofilmlike covering was observed over the bladder surface. Furthermore, large numbers of C. albicans cells were dispersed into the urine from either the catheter or bladder wall biofilm over the infection period. We successfully utilized the model to test the efficacy of antifungals, analyze transcriptional patterns, and examine the phenotype of a genetic mutant. The model should be useful for future investigations involving the pathogenesis, diagnosis, therapy, prevention, and drug resistance of Candida biofilms in the urinary tract. PMID:25183731

Enteroaggregative Escherichia coli (EAEC) impairs growth while malnutrition worsens EAEC infection: a novel murine model of the infection malnutrition cycle.

PubMed

Roche, James K; Cabel, Ace; Sevilleja, Jesus; Nataro, James; Guerrant, Richard L

2010-08-15

Enteroaggregative Escherichia coli is emerging as an increasingly recognized cause of persistent, mildly inflammatory diarrhea in the United States, especially among patients with AIDS, as well as among children, for whom it is accompanied by growth shortfalls. We describe a novel model of disease induced in neonatal and weaned C57BL/6 mice by pathogenic strains of enteroaggregative E. coli 042 and JM221. Enteroaggregative E. coli caused growth impairment (up to 47%), persistent stool shedding (for >3 weeks), and a substantial tissue burden of organisms (150,000 organisms per milligram of tissue), as well as histopathological changes in the colonic epithelium (days 4 and 6 of infection) using the model. Undernutrition in neonatal mice, as well as in weaned mice, intensified infection by 1-4 logs, as assessed by quantitative polymerase chain reaction for fecal shedding of organisms. Growth impairment was dependent on both microorganism burden and challenge dose. Both neonatal and weaned mice provide models for a vicious cycle of enteroaggregative E. coli infection that causes growth shortfalls and undernutrition, thus worsening infection. Hence, these neonatal and weaned mice provide the opportunity to dissect mechanisms of this cycle in childhood malnutrition, as well as to define the role played by innate and acquired host defenses in this important infection.

Mouse infection models for space flight immunology

NASA Technical Reports Server (NTRS)

Chapes, Stephen Keith; Ganta, Roman Reddy; Chapers, S. K. (Principal Investigator)

2005-01-01

Several immunological processes can be affected by space flight. However, there is little evidence to suggest that flight-induced immunological deficits lead to illness. Therefore, one of our goals has been to define models to examine host resistance during space flight. Our working hypothesis is that space flight crews will come from a heterogeneous population; the immune response gene make-up will be quite varied. It is unknown how much the immune response gene variation contributes to the potential threat from infectious organisms, allergic responses or other long term health problems (e.g. cancer). This article details recent efforts of the Kansas State University gravitational immunology group to assess how population heterogeneity impacts host health, either in laboratory experimental situations and/or using the skeletal unloading model of space-flight stress. This paper details our use of several mouse strains with several different genotypes. In particular, mice with varying MHCII allotypes and mice on the C57BL background with different genetic defects have been particularly useful tools with which to study infections by Staphylococcus aureus, Salmonella typhimurium, Pasteurella pneumotropica and Ehrlichia chaffeensis. We propose that some of these experimental challenge models will be useful to assess the effects of space flight on host resistance to infection.

Global stability of a multiple delayed viral infection model with general incidence rate and an application to HIV infection.

PubMed

Ji, Yu

2015-06-01

In this paper, the dynamical behavior of a viral infection model with general incidence rate and two time delays is studied. By using the Lyapunov functional and LaSalle invariance principle, the global stabilities of the infection-free equilibrium and the endemic equilibrium are obtained. We obtain a threshold of the global stability for the uninfected equilibrium, which means the disease will be under control eventually. These results can be applied to a variety of viral infections of disease that would make it possible to devise optimal treatment strategies. Numerical simulations with application to HIV infection are given to verify the analytical results.

Animal model of alcoholic pancreatitis: role of viral infections.

PubMed

Jerrells, Thomas R; Chapman, Nora; Clemens, Dahn L

2003-11-01

Pancreatitis is clearly associated with alcohol abuse, but only a relatively small percentage of people who abuse alcohol develops obvious pancreatitis. These observations have led to the concept that the development of alcoholic pancreatitis requires cofactors. Although diet and smoking have been studied, a clear cofactor has not been identified. The study results presented in this paper were obtained to determine whether viral infection of the pancreas would be a cofactor for alcoholic pancreatitis similar to the role of hepatitis virus infections in the development of alcoholic liver disease. To test this hypothesis, mice were fed ethanol with a liquid diet protocol and infected with coxsackievirus B3 (CVB3). It was found that consumption of alcohol alone did not result in pancreatitis as determined by serum levels of amylase or histologic changes in the pancreas. Two strains of CVB3 that are tropic for the pancreas were used; a virulent and an avirulent strain. Infection of alcohol-fed animals with the virulent CVB3 strain 28 resulted in a more severe pancreatitis than the pancreatitis noted in control animals. Alcohol-fed mice infected with the avirulent strain (GA) showed severe pancreatitis, whereas the infection of control mice did not result in obvious pathologic effects in the pancreas. This model allows mechanistic studies to define the role of viral infection as a cofactor for alcoholic pancreatitis.

Evaluating the Risks: A Bernoulli Process Model of HIV Infection and Risk Reduction.

ERIC Educational Resources Information Center

Pinkerton, Steven D.; Abramson, Paul R.

1993-01-01

A Bernoulli process model of human immunodeficiency virus (HIV) is used to evaluate infection risks associated with various sexual behaviors (condom use, abstinence, or monogamy). Results suggest that infection is best mitigated through measures that decrease infectivity, such as condom use. (SLD)

Modeling the Disease Course of Zaire ebolavirus Infection in the Outbred Guinea Pig.

PubMed

Cross, Robert W; Fenton, Karla A; Geisbert, Joan B; Mire, Chad E; Geisbert, Thomas W

2015-10-01

Rodent models that accurately reflect human filovirus infection are needed as early screens for medical countermeasures. Prior work in rodents with the Zaire species of Ebola virus (ZEBOV) primarily used inbred mice and guinea pigs to model disease. However, these inbred species do not show some of the important features of primate ZEBOV infection, most notably, coagulation abnormalities. Thirty-six outbred guinea pigs were infected with guinea pig-adapted ZEBOV and examined sequentially over an 8-day period to investigate the pathologic events that lead to death. Features of disease in ZEBOV-infected outbred guinea pigs were largely consistent with disease in humans and nonhuman primates and included early infection of macrophages and dendritiform cells, apoptosis of bystander lymphocytes, and increases in levels of proinflammatory cytokines. Most importantly, dysregulation of circulating levels of fibrinogen, protein C activity, and antifibrinolytic proteins and deposition of fibrin in tissues demonstrated both biochemical and microscopic evidence of disseminated intravascular coagulation. These findings suggest that the outbred guinea pig model recapitulates ZEBOV infection of primates better than inbred rodent models, is useful for dissecting key events in the pathogenesis of ZEBOV, and is useful for evaluating candidate interventions prior to assessment in primates. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Dynamics of an HBV/HCV infection model with intracellular delay and cell proliferation

NASA Astrophysics Data System (ADS)

Zhang, Fengqin; Li, Jianquan; Zheng, Chongwu; Wang, Lin

2017-01-01

A new mathematical model of hepatitis B/C virus (HBV/HCV) infection which incorporates the proliferation of healthy hepatocyte cells and the latent period of infected hepatocyte cells is proposed and studied. The dynamics is analyzed via Pontryagin's method and a newly proposed alternative geometric stability switch criterion. Sharp conditions ensuring stability of the infection persistent equilibrium are derived by applying Pontryagin's method. Using the intracellular delay as the bifurcation parameter and applying an alternative geometric stability switch criterion, we show that the HBV/HCV infection model undergoes stability switches. Furthermore, numerical simulations illustrate that the intracellular delay can induce complex dynamics such as persistence bubbles and chaos.

Impact of Vaccination on 14 High-Risk HPV Type Infections: A Mathematical Modelling Approach

PubMed Central

Vänskä, Simopekka; Auranen, Kari; Leino, Tuija; Salo, Heini; Nieminen, Pekka; Kilpi, Terhi; Tiihonen, Petri; Apter, Dan; Lehtinen, Matti

2013-01-01

The development of high-risk human papillomavirus (hrHPV) infection to cervical cancer is a complicated process. We considered solely hrHPV infections, thus avoiding the confounding effects of disease progression, screening, and treatments. To analyse hrHPV epidemiology and to estimate the overall impact of vaccination against infections with hrHPVs, we developed a dynamic compartmental transmission model for single and multiple infections with 14 hrHPV types. The infection-related parameters were estimated using population-based sexual behaviour and hrHPV prevalence data from Finland. The analysis disclosed the important role of persistent infections in hrHPV epidemiology, provided further evidence for a significant natural immunity, and demonstrated the dependence of transmission probability estimates on the model structure. The model predicted that vaccinating girls at 80% coverage will result in a 55% reduction in the overall hrHPV prevalence and a higher 65% reduction in the prevalence of persistent hrHPV infections in females. In males, the reduction will be 42% in the hrHPV prevalence solely by the herd effect from the 80% coverage in girls. If such high coverage among girls is not reached, it is still possible to reduce the female hrHPV prevalence indirectly by the herd effect if also boys are included in the vaccination program. On the other hand, any herd effects in older unvaccinated cohorts were minor. Limiting the epidemiological model to infection yielded improved understanding of the hrHPV epidemiology and of mechanisms with which vaccination impacts on hrHPV infections. PMID:24009669

Takeover times for a simple model of network infection.

PubMed

Ottino-Löffler, Bertrand; Scott, Jacob G; Strogatz, Steven H

2017-07-01

We study a stochastic model of infection spreading on a network. At each time step a node is chosen at random, along with one of its neighbors. If the node is infected and the neighbor is susceptible, the neighbor becomes infected. How many time steps T does it take to completely infect a network of N nodes, starting from a single infected node? An analogy to the classic "coupon collector" problem of probability theory reveals that the takeover time T is dominated by extremal behavior, either when there are only a few infected nodes near the start of the process or a few susceptible nodes near the end. We show that for N≫1, the takeover time T is distributed as a Gumbel distribution for the star graph, as the convolution of two Gumbel distributions for a complete graph and an Erdős-Rényi random graph, as a normal for a one-dimensional ring and a two-dimensional lattice, and as a family of intermediate skewed distributions for d-dimensional lattices with d≥3 (these distributions approach the convolution of two Gumbel distributions as d approaches infinity). Connections to evolutionary dynamics, cancer, incubation periods of infectious diseases, first-passage percolation, and other spreading phenomena in biology and physics are discussed.

Takeover times for a simple model of network infection

NASA Astrophysics Data System (ADS)

Ottino-Löffler, Bertrand; Scott, Jacob G.; Strogatz, Steven H.

2017-07-01

We study a stochastic model of infection spreading on a network. At each time step a node is chosen at random, along with one of its neighbors. If the node is infected and the neighbor is susceptible, the neighbor becomes infected. How many time steps T does it take to completely infect a network of N nodes, starting from a single infected node? An analogy to the classic "coupon collector" problem of probability theory reveals that the takeover time T is dominated by extremal behavior, either when there are only a few infected nodes near the start of the process or a few susceptible nodes near the end. We show that for N ≫1 , the takeover time T is distributed as a Gumbel distribution for the star graph, as the convolution of two Gumbel distributions for a complete graph and an Erdős-Rényi random graph, as a normal for a one-dimensional ring and a two-dimensional lattice, and as a family of intermediate skewed distributions for d -dimensional lattices with d ≥3 (these distributions approach the convolution of two Gumbel distributions as d approaches infinity). Connections to evolutionary dynamics, cancer, incubation periods of infectious diseases, first-passage percolation, and other spreading phenomena in biology and physics are discussed.

Parameter estimation and sensitivity analysis in an agent-based model of Leishmania major infection

PubMed Central

Jones, Douglas E.; Dorman, Karin S.

2009-01-01

Computer models of disease take a systems biology approach toward understanding host-pathogen interactions. In particular, data driven computer model calibration is the basis for inference of immunological and pathogen parameters, assessment of model validity, and comparison between alternative models of immune or pathogen behavior. In this paper we describe the calibration and analysis of an agent-based model of Leishmania major infection. A model of macrophage loss following uptake of necrotic tissue is proposed to explain macrophage depletion following peak infection. Using Gaussian processes to approximate the computer code, we perform a sensitivity analysis to identify important parameters and to characterize their influence on the simulated infection. The analysis indicates that increasing growth rate can favor or suppress pathogen loads, depending on the infection stage and the pathogen’s ability to avoid detection. Subsequent calibration of the model against previously published biological observations suggests that L. major has a relatively slow growth rate and can replicate for an extended period of time before damaging the host cell. PMID:19837088

Serum Metabolomics Investigation of Humanized Mouse Model of Dengue Virus Infection.

PubMed

Cui, Liang; Hou, Jue; Fang, Jinling; Lee, Yie Hou; Costa, Vivian Vasconcelos; Wong, Lan Hiong; Chen, Qingfeng; Ooi, Eng Eong; Tannenbaum, Steven R; Chen, Jianzhu; Ong, Choon Nam

2017-07-15

Dengue is an acute febrile illness caused by dengue virus (DENV) and a major cause of morbidity and mortality in tropical and subtropical regions of the world. The lack of an appropriate small-animal model of dengue infection has greatly hindered the study of dengue pathogenesis and the development of therapeutics. In this study, we conducted mass spectrometry-based serum metabolic profiling from a model using humanized mice (humice) with DENV serotype 2 infection at 0, 3, 7, 14, and 28 days postinfection (dpi). Forty-eight differential metabolites were identified, including fatty acids, purines and pyrimidines, acylcarnitines, acylglycines, phospholipids, sphingolipids, amino acids and derivatives, free fatty acids, and bile acid. These metabolites showed a reversible-change trend-most were significantly perturbed at 3 or 7 dpi and returned to control levels at 14 or 28 dpi, indicating that the metabolites might serve as prognostic markers of the disease in humice. The major perturbed metabolic pathways included purine and pyrimidine metabolism, fatty acid β-oxidation, phospholipid catabolism, arachidonic acid and linoleic acid metabolism, sphingolipid metabolism, tryptophan metabolism, phenylalanine metabolism, lysine biosynthesis and degradation, and bile acid biosynthesis. Most of these disturbed pathways are similar to our previous metabolomics findings in a longitudinal cohort of adult human dengue patients across different infection stages. Our analyses revealed the commonalities of host responses to DENV infection between humice and humans and suggested that humice could be a useful small-animal model for the study of dengue pathogenesis and the development of dengue therapeutics. IMPORTANCE Dengue virus is the most widespread arbovirus, causing an estimated 390 million dengue infections worldwide every year. There is currently no effective treatment for the disease, and the lack of an appropriate small-animal model of dengue infection has greatly

Immunoproteomic profiling of Saccharomyces cerevisiae systemic infection in a murine model.

PubMed

Hernández-Haro, Carolina; Llopis, Silvia; Molina, María; Monteoliva, Lucía; Gil, Concha

2015-01-01

Saccharomyces cerevisiae is considered a safe microorganism widely used as a dietary supplement. However, in the latest decades several cases of S. cerevisiae infections have been reported. Recent studies in a murine model of systemic infection have also revealed the virulence of some S. cerevisiae dietary strains. Here we use an immunoproteomic approach based on protein separation by 2D-PAGE followed by Western-blotting to compare the serological response against a virulent dietary and a non-virulent laboratory strains leading to the identification of highly different patterns of antigenic proteins. Thirty-six proteins that elicit a serological response in mice have been identified. Most of them are involved in stress responses and metabolic pathways. Their selectivity as putative biomarkers for S. cerevisiae infections was assessed by testing sera from S. cerevisiae-infected mice against Candida albicans and C. glabrata proteins. Some chaperones and metabolic proteins showed cross-reactivity. We also compare the S. cerevisiae immunodetected proteins with previously described C. albicans antigens. The results point to the stress-related proteins Ahp1, Yhb1 and Oye2, as well as the glutamine synthetase Gln1 and the oxysosterol binding protein Kes1 as putative candidates for being evaluated as biomarkers for diagnostic assays of S. cerevisiae infections. S. cerevisiae can cause opportunistic infections, and therefore, a precise diagnosis of fungal infections is necessary. This immunoproteomic analysis of sera from a model murine infection with a virulent dietary S. cerevisiae strain has been shown to be a source of candidate proteins for being evaluated as biomarkers to develop assays for diagnosis of S. cerevisiae infections. To our knowledge, this is the first study devoted to the identification of S. cerevisiae immunogenic proteins and the results allowed the proposal of five antigens to be further investigated. Copyright © 2014 Elsevier B.V. All rights reserved.

Mouse model for acute Epstein-Barr virus infection.

PubMed

Wirtz, Tristan; Weber, Timm; Kracker, Sven; Sommermann, Thomas; Rajewsky, Klaus; Yasuda, Tomoharu

2016-11-29

Epstein-Barr Virus (EBV) infects human B cells and drives them into continuous proliferation. Two key viral factors in this process are the latent membrane proteins LMP1 and LMP2A, which mimic constitutively activated CD40 receptor and B-cell receptor signaling, respectively. EBV-infected B cells elicit a powerful T-cell response that clears the infected B cells and leads to life-long immunity. Insufficient immune surveillance of EBV-infected B cells causes life-threatening lymphoproliferative disorders, including mostly germinal center (GC)-derived B-cell lymphomas. We have modeled acute EBV infection of naive and GC B cells in mice through timed expression of LMP1 and LMP2A. Although lethal when induced in all B cells, induction of LMP1 and LMP2A in just a small fraction of naive B cells initiated a phase of rapid B-cell expansion followed by a proliferative T-cell response, clearing the LMP-expressing B cells. Interfering with T-cell activity prevented clearance of LMP-expressing B cells. This was also true for perforin deficiency, which in the human causes a life-threatening EBV-related immunoproliferative syndrome. LMP expression in GC B cells impeded the GC reaction but, upon loss of T-cell surveillance, led to fatal B-cell expansion. Thus, timed expression of LMP1 together with LMP2A in subsets of mouse B cells allows one to study major clinically relevant features of human EBV infection in vivo, opening the way to new therapeutic approaches.

Cost-Effectiveness of a Model Infection Control Program for Preventing Multi-Drug-Resistant Organism Infections in Critically Ill Surgical Patients.

PubMed

Jayaraman, Sudha P; Jiang, Yushan; Resch, Stephen; Askari, Reza; Klompas, Michael

2016-10-01

Interventions to contain two multi-drug-resistant Acinetobacter (MDRA) outbreaks reduced the incidence of multi-drug-resistant (MDR) organisms, specifically methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, and Clostridium difficile in the general surgery intensive care unit (ICU) of our hospital. We therefore conducted a cost-effective analysis of a proactive model infection-control program to reduce transmission of MDR organisms based on the practices used to control the MDRA outbreak. We created a model of a proactive infection control program based on the 2011 MDRA outbreak response. We built a decision analysis model and performed univariable and probabilistic sensitivity analyses to evaluate the cost-effectiveness of the proposed program compared with standard infection control practices to reduce transmission of these MDR organisms. The cost of a proactive infection control program would be $68,509 per year. The incremental cost-effectiveness ratio (ICER) was calculated to be $3,804 per aversion of transmission of MDR organisms in a one-year period compared with standard infection control. On the basis of probabilistic sensitivity analysis, a willingness-to-pay (WTP) threshold of $14,000 per transmission averted would have a 42% probability of being cost-effective, rising to 100% at $22,000 per transmission averted. This analysis gives an estimated ICER for implementing a proactive program to prevent transmission of MDR organisms in the general surgery ICU. To better understand the causal relations between the critical steps in the program and the rate reductions, a randomized study of a package of interventions to prevent healthcare-associated infections should be considered.

Stochastic modeling for dynamics of HIV-1 infection using cellular automata: A review.

PubMed

Precharattana, Monamorn

2016-02-01

Recently, the description of immune response by discrete models has emerged to play an important role to study the problems in the area of human immunodeficiency virus type 1 (HIV-1) infection, leading to AIDS. As infection of target immune cells by HIV-1 mainly takes place in the lymphoid tissue, cellular automata (CA) models thus represent a significant step in understanding when the infected population is dispersed. Motivated by these, the studies of the dynamics of HIV-1 infection using CA in memory have been presented to recognize how CA have been developed for HIV-1 dynamics, which issues have been studied already and which issues still are objectives in future studies.

Spread of Ebola disease with susceptible exposed infected isolated recovered (SEIIhR) model

NASA Astrophysics Data System (ADS)

Azizah, Afina; Widyaningsih, Purnami; Retno Sari Saputro, Dewi

2017-06-01

Ebola is a deadly infectious disease and has caused an epidemic on several countries in West Africa. Mathematical modeling to study the spread of Ebola disease has been developed, including through models susceptible infected removed (SIR) and susceptible exposed infected removed (SEIR). Furthermore, susceptible exposed infected isolated recovered (SEIIhR) model has been derived. The aims of this research are to derive SEIIhR model for Ebola disease, to determine the patterns of its spread, to determine the equilibrium point and stability of the equilibrium point using phase plane analysis, and also to apply the SEIIhR model on Ebola epidemic in Sierra Leone in 2014. The SEIIhR model is a differential equation system. Pattern of ebola disease spread with SEIIhR model is solution of the differential equation system. The equilibrium point of SEIIhR model is unique and it is a disease-free equilibrium point that stable. Application of the model is based on the data Ebola epidemic in Sierra Leone. The free-disease equilibrium point (Se; Ee; Ie; Ihe; Re )=(5743865, 0, 0, 0, 0) is stable.

In Vivo Activities of Amoxicillin and Amoxicillin-Clavulanate against Streptococcus pneumoniae: Application to Breakpoint Determinations

PubMed Central

Andes, D.; Craig, W. A.

1998-01-01

The in vivo activities of amoxicillin and amoxicillin-clavulanate against 17 strains of Streptococcus pneumoniae with penicillin MICs of 0.12–8.0 mg/liter were assessed in a cyclophosphamide-induced neutropenic murine thigh infection model. Renal impairment was produced by administration of uranyl nitrate to prolong the amoxicillin half-life in the mice from 21 to 65 min, simulating human pharmacokinetics. Two hours after thigh infection with 105 to 106 CFU, groups of mice were treated with 7 mg of amoxicillin per kg of body weight alone or combined with clavulanate (ratio, 4:1) every 8 h for 1 and 4 days. There was an excellent correlation between the MIC of amoxicillin (0.03 to 5.6 mg/liter) and (i) the change in log10 CFU/thigh at 24 h and (ii) survival after 4 days of therapy. Organisms for which MICs were 2 mg/liter or less were killed at 1.4 to 4.2 and 1.6 to 4.1 log10 CFU/thigh at 24 h by amoxicillin and amoxicillin-clavulanate, respectively. The four strains for which MICs were >4 mg/liter grew 0.2 to 2.6 and 0.6 to 2.3 logs at 24 h despite therapy with amoxicillin and amoxicillin-clavulanate, respectively. Infection was uniformly fatal by 72 h in untreated mice. Amoxicillin therapy resulted in no mortality with organisms for which MICs were 1 mg/liter or less, 20 to 40% mortality with organisms for which MICs were 2 mg/liter, and 80 to 100% mortality with organisms for which MICs were 4.0–5.6 mg/liter. Lower and higher doses (0.5, 2, and 20 mg/kg) of amoxicillin were studied against organisms for which MICs were near the breakpoint. These studies demonstrate that a reduction of 1 log10 or greater in CFU/thigh at 24 h is consistently observed when amoxicillin levels exceed the MIC for 25 to 30% of the dosing interval. These studies would support amoxicillin (and amoxicillin-clavulanate) MIC breakpoints of 1 mg/liter for susceptible, 2 mg/liter for intermediate, and 4 mg/liter for resistant strains of S. pneumoniae. PMID:9736566

[Modified anterolateral thigh perforator flap pedicled by cross-bridge microvascular anastomosis for repairing soft tissue defects in middle and lower segments of leg].

PubMed

Yang, Lin; Liu, Hongjun; Zhang, Wenzhong; Song, Guoxun; Xia, Shicong; Zhang, Naichen; Gu, Jiaxiang; Yuan, Chaoqun

2017-10-01

To explore the effectiveness of modified anterolateral thigh perforator flap pedicled by cross-bridge microvascular anastomosis in treatment of soft tissue defects in the middle and lower segments of the leg. Between March 2011 and June 2015, 15 cases with skin and soft tissue defects in the middle and lower segments of the legs were treated. There were 9 males and 6 females, aged 22-48 years (mean, 32.6 years). Of whom, 8 patients caused by traffic accidents, 5 by machine twist, and 2 by crash injury of heavy object. The mean interval from injury to admission was 82.6 hours (range, 2 hours to 1 week). The area of defect ranged from 13 cm×9 cm to 23 cm×16 cm. After primary debridement and vaccum sealing drainage treatment, the defects were repaired with modified anterolateral thigh perforator flap pedicled by cross-bridge microvascular anastomosis. The size of flap ranged from 15 cm×10 cm to 25 cm×15 cm. The donor sites were sutured directly or repaired with the skin grafts. The pedicle division was done at 4 weeks after operation. After operation, venous crisis occurred in 1 case and distal skin necrosis in 2 cases which was healed by dressing change. The other tissue flaps survived successfully and wounds healed by first intention. All skin grafts at donor site survived after operation, and primary healing of wound was obtained. All patients were followed up 6-24 months (mean, 13 months). All flaps were characterized by soft texture, satisfactory appearance, and restoring the protective sensation. Moreover, the two-point discrimination ranged from 15 to 28 mm (mean, 19.5 mm) at 6 months after operation. The function of both lower extremities were normal without obvious contracture of scar at donor site. Modified free anterolateral thigh perforator flap, with little damage in donor site, a reliable blood supply by making a cross-bridge microvascular anastomosis with pretibial or posterior tibial blood vessel on normal leg, is a reliable alternative method for

Building predictive models for MERS-CoV infections using data mining techniques.

PubMed

Al-Turaiki, Isra; Alshahrani, Mona; Almutairi, Tahani

Recently, the outbreak of MERS-CoV infections caused worldwide attention to Saudi Arabia. The novel virus belongs to the coronaviruses family, which is responsible for causing mild to moderate colds. The control and command center of Saudi Ministry of Health issues a daily report on MERS-CoV infection cases. The infection with MERS-CoV can lead to fatal complications, however little information is known about this novel virus. In this paper, we apply two data mining techniques in order to better understand the stability and the possibility of recovery from MERS-CoV infections. The Naive Bayes classifier and J48 decision tree algorithm were used to build our models. The dataset used consists of 1082 records of cases reported between 2013 and 2015. In order to build our prediction models, we split the dataset into two groups. The first group combined recovery and death records. A new attribute was created to indicate the record type, such that the dataset can be used to predict the recovery from MERS-CoV. The second group contained the new case records to be used to predict the stability of the infection based on the current status attribute. The resulting recovery models indicate that healthcare workers are more likely to survive. This could be due to the vaccinations that healthcare workers are required to get on regular basis. As for the stability models using J48, two attributes were found to be important for predicting stability: symptomatic and age. Old patients are at high risk of developing MERS-CoV complications. Finally, the performance of all the models was evaluated using three measures: accuracy, precision, and recall. In general, the accuracy of the models is between 53.6% and 71.58%. We believe that the performance of the prediction models can be enhanced with the use of more patient data. As future work, we plan to directly contact hospitals in Riyadh in order to collect more information related to patients with MERS-CoV infections. Copyright © 2016

A mouse model for Chlamydia suis genital infection.

PubMed

Donati, Manuela; Di Paolo, Maria; Favaroni, Alison; Aldini, Rita; Di Francesco, Antonietta; Ostanello, Fabio; Biondi, Roberta; Cremonini, Eleonora; Ginocchietti, Laura; Cevenini, Roberto

2015-02-01

A mouse model for Chlamydia suis genital infection was developed. Ninety-nine mice were randomly divided into three groups and intravaginally inoculated with chlamydia: 45 mice (group 1) received C. suis purified elementary bodies (EBs), 27 (group 2) were inoculated with C. trachomatis genotype E EBs and 27 mice (group 3) with C. trachomatis genotype F EBs. Additionally, 10 mice were used as a negative control. At seven days post-infection (dpi) secretory anti-C. suis IgA were recovered from vaginal swabs of all C. suis inoculated mice. Chlamydia suis was isolated from 93, 84, 71 and 33% vaginal swabs at 3, 5, 7 and 12 dpi. Chlamydia trachomatis genotype E and F were isolated from 100% vaginal swabs up to 7 dpi and from 61 and 72%, respectively, at 12 dpi. Viable C. suis and C. trachomatis organisms were isolated from uterus and tubes up to 16 and 28 dpi, respectively. The results of the present study show the susceptibility of mice to intravaginal inoculation with C. suis. A more rapid course and resolution of C. suis infection, in comparison to C. trachomatis, was highlighted. The mouse model could be useful for comparative investigations involving C. suis and C. trachomatis species. © FEMS 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The rabbit as an infection model for equine proliferative enteropathy

PubMed Central

Sampieri, Francesca; Allen, Andrew L.; Pusterla, Nicola; Vannucci, Fabio A.; Antonopoulos, Aphroditi J.; Ball, Katherine R.; Thompson, Julie; Dowling, Patricia M.; Hamilton, Don L.; Gebhart, Connie J.

2013-01-01

The objective of this study was to demonstrate the susceptibility of rabbits to Lawsonia intracellularis obtained from a case of clinical equine proliferative enteropathy (EPE). This is a preliminary step toward developing a rabbit infection model for studying pathogenesis and therapy of EPE in horses. Nine does were equally assigned to 3 groups. Animals in 2 groups (Group 1 and Group 2) were orally inoculated with different doses of cell-cultured L. intracellularis. Controls (Group 3) were sham-inoculated. Feces and blood were collected before the rabbits were infected and at 7, 14, and 21 days post-infection (DPI). Serum immunoglobulin G (IgG) titers were measured using an immunoperoxidase monolayer assay (IPMA) and fecal samples were analyzed with quantitative polymerase chain reaction (qPCR). A doe from each group was euthanized at 7, 14, and 21 DPI for collection and evaluation of intestinal samples. Tissues were stained by routine hematoxylin and eosin (H&E) method and immunohistochemistry (IHC) with L. intracellularis-specific mouse monoclonal antibody. At 14 DPI, serologic responses were detected in both infected groups, which maintained high titers through to 21 DPI. Lawsonia intracellularis DNA was detected in the feces of Group 2 on 7 DPI and in both infected groups on 14 DPI. Gross lesions were apparent in Group 1 and Group 2 on 14 DPI. Immunohistochemistry confirmed L. intracellularis antigen within cells of rabbits in Group 1 and Group 2 on 7, 14, and 21 DPI. No lesions, serologic response, shedding, or IHC labeling were found in Group 3 rabbits. This study describes an EPE rabbit model that simulates natural infection, as typical lesions, immune response, and fecal shedding were present. PMID:24082402

Mid-thigh cortical bone structural parameters, muscle mass and strength, and association with lower limb fractures in older men and women (AGES-Reykjavik Study).

PubMed

Johannesdottir, Fjola; Aspelund, Thor; Siggeirsdottir, Kristin; Jonsson, Brynjolfur Y; Mogensen, Brynjolfur; Sigurdsson, Sigurdur; Harris, Tamara B; Gudnason, Vilmundur G; Lang, Thomas F; Sigurdsson, Gunnar

2012-05-01

In a cross-sectional study we investigated the relationship between muscle and bone parameters in the mid-thigh in older people using data from a single axial computed tomographic section through the mid-thigh. Additionally, we studied the association of these variables with incident low-trauma lower limb fractures. A total of 3,762 older individuals (1,838 men and 1,924 women), aged 66-96 years, participants in the AGES-Reykjavik study, were studied. The total cross-sectional muscular area and knee extensor strength declined with age similarly in both sexes. Muscle parameters correlated most strongly with cortical area and total shaft area (adjusted for age, height, and weight) but explained <10 % of variability in those bone parameters. The increment in medullary area (MA) and buckling ratio (BR) with age was almost fourfold greater in women than men. The association between MA and muscle parameters was nonsignificant. During a median follow-up of 5.3 years, 113 women and 66 men sustained incident lower limb fractures. Small muscular area, low knee extensor strength, large MA, low cortical thickness, and high BR were significantly associated with fractures in both sexes. Our results show that bone and muscle loss proceed at different rates and with different gender patterns.

A multiscale model on hospital infections coupling macro and micro dynamics

NASA Astrophysics Data System (ADS)

Wang, Xia; Tang, Sanyi

2017-09-01

A multiscale model of hospital infections coupling the micro model of the growth of bacteria and the macro model describing the transmission of the bacteria among patients and health care workers (HCWs) was established to investigate the effects of antibiotic treatment on the transmission of the bacteria among patients and HCWs. The model was formulated by viewing the transmission rate from infected patients to HCWs and the shedding rate of bacteria from infected patients to the environment as saturated functions of the within-host bacterial load. The equilibria and the basic reproduction number of the coupled system were studied, and the global dynamics of the disease free equilibrium and the endemic equilibrium were analyzed in detail by constructing two Lyapunov functions. Furthermore, effects of drug treatment in the within-host model on the basic reproduction number and the dynamics of the coupled model were studied by coupling a pharmacokinetics model with the within-host model. Sensitive analysis indicated that the growth rate of the bacteria, the maximum drug effect and the dosing interval are the three most sensitive parameters contributing to the basic reproduction number. Thus, adopting ;wonder; drugs to decrease the growth rate of the bacteria or to increase the drug's effect is the most effective measure but changing the dosage regime is also effective. A quantitative criterion of how to choose the best dosage regimen can also be obtained from numerical results.

[Effects of anteriolateral thigh perforator flap and fascia lata transplantation in combination with computed tomography angiography on repair of electrical burn wounds of head with skull exposure and necrosis].

PubMed

Li, X Q; Wang, X; Han, Y L; Ji, G; Chen, Z H; Zhang, J; Zhu, J P; Duan, J X; He, Y J; Yang, X M; Liu, W J

2018-05-20

Objective: To explore the effects of anteriolateral thigh perforator flap and fascia lata transplantation in combination with computed tomography angiography (CTA) on repair of electrical burn wounds of head with skull exposure and necrosis. Methods: Seven patients with head electrical burns accompanied by skull exposure and necrosis were admitted to our burn center from March 2016 to December 2017. Head CTA was performed before the operation. The diameters of the facial artery and vein or the superficial temporal artery and vein were measured, and their locations were marked on the body surface. Preoperative CTA for flap donor sites in lower extremities were also performed to track the descending branch of the lateral circumflex femoral artery with the similar diameter as the recipient vessels on the head, and their locations were marked on the body surface. Routine wound debridement and skull drilling were performed successively. The size of the wounds after debridement ranged from 12 cm×8 cm to 20 cm×12 cm, and the areas of skull exposure ranged from 8 cm×6 cm to 15 cm×10 cm. Anteriolateral thigh perforator flaps with areas from 13 cm×9 cm to 21 cm×13 cm containing 5-10 cm long vascular pedicles were designed and dissected accordingly. The fascia lata under the flap with area from 5 cm×2 cm to 10 cm×3 cm was dissected according to the length of vascular pedicle. The fascia lata was transplanted to cover the exposed skull, and the anteriolateral thigh perforator flap was transplanted afterwards. The descending branch of the lateral circumflex femoral artery and its accompanying vein of the flap were anastomosed with superficial temporal artery and vein or facial artery and vein before the suture of flap. The flap donor sites were covered by intermediate split-thickness skin graft collected from contralateral thigh or abdomen. Results: The descending branch of the lateral circumflex femoral artery and its accompanying vein were anastomosed with superficial

The oxadiazole antibacterials.

PubMed

Janardhanan, Jeshina; Chang, Mayland; Mobashery, Shahriar

2016-10-01

The oxadiazoles are a class of antibacterials discovered by in silico docking and scoring of compounds against the X-ray structure of a penicillin-binding protein. These antibacterials exhibit activity against Gram-positive bacteria, including against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). They show in vivo efficacy in murine models of peritonitis/sepsis and neutropenic thigh MRSA infection. They are bactericidal and orally bioavailable. The oxadiazoles show promise in treatment of MRSA infection. Copyright © 2016 Elsevier Ltd. All rights reserved.

Smallpox infections during pregnancy, lessons on pathogenesis from nonpregnant animal models of infection.

PubMed

Hassett, Daniel E

2003-10-01

Both vaccinated and unvaccinated women during pregnancy who contract variola virus, the causative agent of smallpox, suffer much higher mortality rates than nonpregnants. Furthermore, acute maternal smallpox leads to spontaneous abortion, premature termination of pregnancy and early postnatal infant mortality. The mechanisms governing the abortifacient activity of smallpox, as well as the enhanced susceptibility of gestating women to lethal disease, have remained largely unexamined. Experimental poxvirus infections in nonpregnant small animal models have revealed that T helper type 1 (TH1) cytokines promote efficient resolution of these infections whereas type 2 (TH2) cytokines enhance viral pathogenesis. These data, combined with recent understanding of how the immune system is modulated by pregnancy, may offer important clues as to the increased pathogenesis of variola in pregnant women. The aim of this review is to bring together the current literature on the effects of poxvirus infections in nonpregnant hosts, as well as the effects of pregnancy on the immune system, in order to develop unifying concepts that may provide insight into the pathogenesis of variola during pregnancy and why prior vaccination with vaccinia virus the live anti-variola vaccine offers less protection to pregnant women and their unborn children.

Outcome Prediction in Mathematical Models of Immune Response to Infection.

PubMed

Mai, Manuel; Wang, Kun; Huber, Greg; Kirby, Michael; Shattuck, Mark D; O'Hern, Corey S

2015-01-01

Clinicians need to predict patient outcomes with high accuracy as early as possible after disease inception. In this manuscript, we show that patient-to-patient variability sets a fundamental limit on outcome prediction accuracy for a general class of mathematical models for the immune response to infection. However, accuracy can be increased at the expense of delayed prognosis. We investigate several systems of ordinary differential equations (ODEs) that model the host immune response to a pathogen load. Advantages of systems of ODEs for investigating the immune response to infection include the ability to collect data on large numbers of 'virtual patients', each with a given set of model parameters, and obtain many time points during the course of the infection. We implement patient-to-patient variability v in the ODE models by randomly selecting the model parameters from distributions with coefficients of variation v that are centered on physiological values. We use logistic regression with one-versus-all classification to predict the discrete steady-state outcomes of the system. We find that the prediction algorithm achieves near 100% accuracy for v = 0, and the accuracy decreases with increasing v for all ODE models studied. The fact that multiple steady-state outcomes can be obtained for a given initial condition, i.e. the basins of attraction overlap in the space of initial conditions, limits the prediction accuracy for v > 0. Increasing the elapsed time of the variables used to train and test the classifier, increases the prediction accuracy, while adding explicit external noise to the ODE models decreases the prediction accuracy. Our results quantify the competition between early prognosis and high prediction accuracy that is frequently encountered by clinicians.

Evaluation of Mouse Wound Models for Probiotics-Based Wound Infection Prevention Study

DTIC Science & Technology

2016-06-01

Martinez MA, Valdez JC. Bacteriotherapy with Lactobacillus plantarum in burns. Int Wound J. 2009; 6(1):73-81. 3. Valdéz JC, Peral MC, Rachid M...Santana M, Perdigón G. Interference of Lactobacillus plantarum with Pseudomonas aeruginosa in vitro and in infected burns: the potential use of...used. The punch and skin flap models are reproducible murine models for wounding and infection. The use of probiotic ( Lactobacillus reuteri) had

Association of Enterococcus spp. with Severe Combat Extremity Injury, Intensive Care, and Polymicrobial Wound Infection.

PubMed

Heitkamp, Rae A; Li, Ping; Mende, Katrin; Demons, Samandra T; Tribble, David R; Tyner, Stuart D

2018-01-01

Combat-related extremity wound infections can complicate the recovery of injured military personnel. The Enterococcus genus contains both commensal and pathogenic bacteria found in many combat wounds. We describe the patient population susceptible to Enterococcus infection, the characteristics of Enterococcus spp. isolated from combat-related wounds, and the microbiological profile of Enterococcus-positive wounds. Patient and culture data were obtained from the Trauma Infectious Disease Outcomes Study. Subjects were divided into a case group with enterococcal extremity wound infections and a comparator group with wound infections caused by other micro-organisms. Case and comparator subjects had similar patterns of injury and infection. Case subjects had higher Injury Severity Scores (33 vs. 30; p < 0.001), longer hospitalization at U.S. facilities (55 vs. 40 days; p = 0.004), and required more large-volume blood transfusions (>20 units) within 24 h post-injury (53% vs. 30%; p < 0.001). Approximately 60% of case subjects had three or more infections, and 91% had one or more polymicrobial infections, compared with 43% and 50%, respectively, in the comparator group. The thigh was the most common site of Enterococcus spp. isolation, contributing 50% of isolates. Enterococcus faecium was the predominant species isolated from case-group infections overall (66%), as well as in polymicrobial infections (74%). Frequent co-colonizing microbes in polymicrobial wound infections with Enterococcus were other ESKAPE pathogens (64%) (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae [and Escherichia coli], Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) and fungi (35%). The specific pathogenicity of Enterococcus relative to other pathogens in polymicrobial wounds is unknown. Identifying strain-specific outcomes and investigating the interactions of Enterococcus strains with other wound pathogens could provide additional tools

Lower limb gigantism, lymphedema, and painful varicosities following a thigh vascular access graft.

PubMed

Thompson, Michael; Mathuram Thiyagarajan, Umasankar; Akoh, Jacob A

2014-07-01

Prosthetic arteriovenous grafts (AVGs) are associated with greater morbidity than autogenous arteriovenous fistulas (AVFs), but their use is indicated when AVF formation is not possible. This report adds to the literature a case of lower limb gigantism, painful varicosities, and lymphedema following long-term use of AVG in the upper thigh. The patient's past medical history included renal transplantation on the same side well before the AVG was inserted and right leg deep vein thrombosis. Suspicion of AVG thrombosis was excluded by Doppler ultrasound, which demonstrated an access flow of 1700 mL/min. A computed tomography (CT) scan of the abdomen and pelvis did not identify the cause of her symptoms. Whereas functional incompetence of the iliac vein valve might be responsible for the varicosities, the extent of hypertrophy in this case raises the suspicion of lymphatic blockage possibly secondary to groin dissection undertaken at the time of graft insertion, in addition to the previous dissection at the time of transplantation. This case highlights the need for minimal groin dissection during AVG insertion, particularly in patients with a history of previous abdominopelvic surgery. © 2014 International Society for Hemodialysis.

Sudden spreading of infections in an epidemic model with a finite seed fraction

NASA Astrophysics Data System (ADS)

Hasegawa, Takehisa; Nemoto, Koji

2018-03-01

We study a simple case of the susceptible-weakened-infected-removed model in regular random graphs in a situation where an epidemic starts from a finite fraction of initially infected nodes (seeds). Previous studies have shown that, assuming a single seed, this model exhibits a kind of discontinuous transition at a certain value of infection rate. Performing Monte Carlo simulations and evaluating approximate master equations, we find that the present model has two critical infection rates for the case with a finite seed fraction. At the first critical rate the system shows a percolation transition of clusters composed of removed nodes, and at the second critical rate, which is larger than the first one, a giant cluster suddenly grows and the order parameter jumps even though it has been already rising. Numerical evaluation of the master equations shows that such sudden epidemic spreading does occur if the degree of the underlying network is large and the seed fraction is small.

The Microminipig as an Animal Model for Influenza A Virus Infection

PubMed Central

Nakajima, Noriko; Shibata, Masatoshi; Takahashi, Kenta; Sato, Yuko; Kiso, Maki; Yamayoshi, Seiya; Ito, Mutsumi; Enya, Satoko; Otake, Masayoshi; Kangawa, Akihisa; da Silva Lopes, Tiago Jose; Ito, Hirotaka; Hasegawa, Hideki

2016-01-01

ABSTRACT Pigs are considered a mixing vessel for the generation of novel pandemic influenza A viruses through reassortment because of their susceptibility to both avian and human influenza viruses. However, experiments to understand reassortment in pigs in detail have been limited because experiments with regular-sized pigs are difficult to perform. Miniature pigs have been used as an experimental animal model, but they are still large and require relatively large cages for housing. The microminipig is one of the smallest miniature pigs used for experiments. Introduced in 2010, microminipigs weigh around 10 kg at an early stage of maturity (6 to 7 months old) and are easy to handle. To evaluate the microminipig as an animal model for influenza A virus infection, we compared the receptor distribution of 10-week-old male pigs (Yorkshire Large White) and microminipigs. We found that both animals have SAα2,3Gal and SAα2,6Gal in their respiratory tracts, with similar distributions of both receptor types. We further found that the sensitivity of microminipigs to influenza A viruses was the same as that of larger miniature pigs. Our findings indicate that the microminipig could serve as a novel model animal for influenza A virus infection. IMPORTANCE The microminipig is one of the smallest miniature pigs in the world and is used as an experimental animal model for life science research. In this study, we evaluated the microminipig as a novel animal model for influenza A virus infection. The distribution of influenza virus receptors in the respiratory tract of the microminipig was similar to that of the pig, and the sensitivity of microminipigs to influenza A viruses was the same as that of miniature pigs. Our findings suggest that microminipigs represent a novel animal model for influenza A virus infection. PMID:27807225

The Microminipig as an Animal Model for Influenza A Virus Infection.

PubMed

Iwatsuki-Horimoto, Kiyoko; Nakajima, Noriko; Shibata, Masatoshi; Takahashi, Kenta; Sato, Yuko; Kiso, Maki; Yamayoshi, Seiya; Ito, Mutsumi; Enya, Satoko; Otake, Masayoshi; Kangawa, Akihisa; da Silva Lopes, Tiago Jose; Ito, Hirotaka; Hasegawa, Hideki; Kawaoka, Yoshihiro

2017-01-15

Pigs are considered a mixing vessel for the generation of novel pandemic influenza A viruses through reassortment because of their susceptibility to both avian and human influenza viruses. However, experiments to understand reassortment in pigs in detail have been limited because experiments with regular-sized pigs are difficult to perform. Miniature pigs have been used as an experimental animal model, but they are still large and require relatively large cages for housing. The microminipig is one of the smallest miniature pigs used for experiments. Introduced in 2010, microminipigs weigh around 10 kg at an early stage of maturity (6 to 7 months old) and are easy to handle. To evaluate the microminipig as an animal model for influenza A virus infection, we compared the receptor distribution of 10-week-old male pigs (Yorkshire Large White) and microminipigs. We found that both animals have SAα2,3Gal and SAα2,6Gal in their respiratory tracts, with similar distributions of both receptor types. We further found that the sensitivity of microminipigs to influenza A viruses was the same as that of larger miniature pigs. Our findings indicate that the microminipig could serve as a novel model animal for influenza A virus infection. The microminipig is one of the smallest miniature pigs in the world and is used as an experimental animal model for life science research. In this study, we evaluated the microminipig as a novel animal model for influenza A virus infection. The distribution of influenza virus receptors in the respiratory tract of the microminipig was similar to that of the pig, and the sensitivity of microminipigs to influenza A viruses was the same as that of miniature pigs. Our findings suggest that microminipigs represent a novel animal model for influenza A virus infection. Copyright © 2017 American Society for Microbiology.

Efficiency of prompt quarantine measures on a susceptible-infected-removed model in networks.

PubMed

Hasegawa, Takehisa; Nemoto, Koji

2017-08-01

This study focuses on investigating the manner in which a prompt quarantine measure suppresses epidemics in networks. A simple and ideal quarantine measure is considered in which an individual is detected with a probability immediately after it becomes infected and the detected one and its neighbors are promptly isolated. The efficiency of this quarantine in suppressing a susceptible-infected-removed (SIR) model is tested in random graphs and uncorrelated scale-free networks. Monte Carlo simulations are used to show that the prompt quarantine measure outperforms random and acquaintance preventive vaccination schemes in terms of reducing the number of infected individuals. The epidemic threshold for the SIR model is analytically derived under the quarantine measure, and the theoretical findings indicate that prompt executions of quarantines are highly effective in containing epidemics. Even if infected individuals are detected with a very low probability, the SIR model under a prompt quarantine measure has finite epidemic thresholds in fat-tailed scale-free networks in which an infected individual can always cause an outbreak of a finite relative size without any measure. The numerical simulations also demonstrate that the present quarantine measure is effective in suppressing epidemics in real networks.

Efficiency of prompt quarantine measures on a susceptible-infected-removed model in networks

NASA Astrophysics Data System (ADS)

Hasegawa, Takehisa; Nemoto, Koji

2017-08-01

This study focuses on investigating the manner in which a prompt quarantine measure suppresses epidemics in networks. A simple and ideal quarantine measure is considered in which an individual is detected with a probability immediately after it becomes infected and the detected one and its neighbors are promptly isolated. The efficiency of this quarantine in suppressing a susceptible-infected-removed (SIR) model is tested in random graphs and uncorrelated scale-free networks. Monte Carlo simulations are used to show that the prompt quarantine measure outperforms random and acquaintance preventive vaccination schemes in terms of reducing the number of infected individuals. The epidemic threshold for the SIR model is analytically derived under the quarantine measure, and the theoretical findings indicate that prompt executions of quarantines are highly effective in containing epidemics. Even if infected individuals are detected with a very low probability, the SIR model under a prompt quarantine measure has finite epidemic thresholds in fat-tailed scale-free networks in which an infected individual can always cause an outbreak of a finite relative size without any measure. The numerical simulations also demonstrate that the present quarantine measure is effective in suppressing epidemics in real networks.

Reconstruction of two separate defects in the upper extremity using anterolateral thigh chimeric flap.

PubMed

Peng, Feng; Chen, Lin; Han, Dong; Xiao, Chenwei; Bao, Qiyuan; Wang, Tao

2013-11-01

We presented our experience on the use of anterolateral thigh (ALT) chimeric flap to reconstruct two separate defects in upper extremity. From December 2009 to August 2012, we used this ALT chimeric flap to reconstruct two separate defects in upper extremity on five patients (mean age: 36.6 years; range: 15 ∼ 47 years). The locations of defect were palm and fingers in four patients and forearm in the other patient. The sizes of defect ranged from 4.5 × 1.5 cm to 20 × 10 cm. A minimum of two separate perforator vessels in the flap were identified. The skin paddle was then split between the two perforators to shape two separate paddles with a common vascular supply. There were no cases of flap failure or re-exploration. Four donor sites were directly closed and one was covered by a skin graft. Donor-site morbidity was negligible. The ALT chimeric flap provides customized cover for two separate defects in upper extremity. Copyright © 2013 Wiley Periodicals, Inc.

Resistance to infection of five different materials in a rat body wall model.

PubMed

Medberry, Christopher J; Tottey, Stephen; Jiang, Hongbin; Johnson, Scott A; Badylak, Stephen F

2012-03-01

Infection occurs after approximately 1% of hernia repair procedures. The resistance to infection of the repair materials is therefore an important consideration. We evaluated the infection resistance of five different materials in a rat model of body wall repair, two of which, urinary bladder matrix (UBM-ECM) and Revive, were not previously evaluated in a controlled model of infection. An inoculum of 1 × 10(8) colony forming units of Staphylococcus aureus was delivered to the wound site following implantation of an autograft, UBM-ECM, Proceed, Prolene, or Revive. Infection was monitored by white blood cell counts, body temperature, bacterial culture, and histomorphologic analysis of the implant site. Infection was shown in all groups through increased white blood cell count and body temperature. Animals with UBM-ECM returned to pre-surgery body temperature before all other groups. Substantial bacterial clearance was found in the autograft, UBM-ECM, and Prolene. Histomorphologic analysis showed evidence for persistent bacterial infection in Prolene, Proceed, and Revive 28 d after implantation, whereas the autograft and UBM-ECM appeared free of infection. The autograft showed a pyogranulomatous inflammatory reaction at 28 d while UBM-ECM was similar to uninfected controls. Superior infection resistance was shown by UBM-ECM compared with the other materials, which were substantially equivalent. Histomorphologic analysis clearly showed an increased ability to resist persistent bacterial infection for UBM-ECM. Our results suggest UBM-ECM may be useful as a repair material in areas of high risk for infection. Copyright © 2012 Elsevier Inc. All rights reserved.

Structural equation models to estimate risk of infection and tolerance to bovine mastitis.

PubMed

Detilleux, Johann; Theron, Léonard; Duprez, Jean-Noël; Reding, Edouard; Humblet, Marie-France; Planchon, Viviane; Delfosse, Camille; Bertozzi, Carlo; Mainil, Jacques; Hanzen, Christian

2013-03-06

One method to improve durably animal welfare is to select, as reproducers, animals with the highest ability to resist or tolerate infection. To do so, it is necessary to distinguish direct and indirect mechanisms of resistance and tolerance because selection on these traits is believed to have different epidemiological and evolutionary consequences. We propose structural equation models with latent variables (1) to quantify the latent risk of infection and to identify, among the many potential mediators of infection, the few ones that influence it significantly and (2) to estimate direct and indirect levels of tolerance of animals infected naturally with pathogens. We applied the method to two surveys of bovine mastitis in the Walloon region of Belgium, in which we recorded herd management practices, mastitis frequency, and results of bacteriological analyses of milk samples. Structural equation models suggested that, among more than 35 surveyed herd characteristics, only nine (age, addition of urea in the rations, treatment of subclinical mastitis, presence of dirty liner, cows with hyperkeratotic teats, machine stripping, pre- and post-milking teat disinfection, and housing of milking cows in cubicles) were directly and significantly related to a latent measure of bovine mastitis, and that treatment of subclinical mastitis was involved in the pathway between post-milking teat disinfection and latent mastitis. These models also allowed the separation of direct and indirect effects of bacterial infection on milk productivity. Results suggested that infected cows were tolerant but not resistant to mastitis pathogens. We revealed the advantages of structural equation models, compared to classical models, for dissecting measurements of resistance and tolerance to infectious diseases, here bovine mastitis. Using our method, we identified nine major risk factors that were directly associated with an increased risk of mastitis and suggested that cows were tolerant but

Limited susceptibility and lack of systemic infection by an H3N2 swine influenza virus in intranasally inoculated chickens.

PubMed

Thomas, Colleen; Manin, Timofey B; Andriyasov, Artem V; Swayne, David E

2008-09-01

Chickens were intranasally inoculated with the swine influenza virus (SIV) A/swine/NC/307408/04 (H3N2) (NC/04 SIV) to determine the infectivity of a North American SIV for chickens, as well as the possibility of chicken meat serving as a transmission vehicle for SIV. White leghorn (WL) layer-type chickens were used for initial pathotyping and infectivity tests, and a more comprehensive intranasal pathogenesis study was done with white Plymouth rock (WPR) broiler-type chickens. None of the NC/04 SIV-inoculated WL or WPR chickens displayed clinical signs. Serologic tests showed that the virus was able to infect both intranasally inoculated WL and WPR chickens, but the antibody titers were low, suggesting inefficient replication. Some of the NC/04 SIV-inoculated WL chickens shed low levels of virus, mostly from the alimentary tract, but viral shedding was not detected in NC/04 SIV-inoculated WPR chickens. The comprehensive pathogenesis study demonstrated that the virus did not cause systemic infections in WPR chickens, and feeding breast and thigh meat from the NC/04 SIV-inoculated WPR to WL chickens did not transmit NC/04 SIV.

Animal models for human T-lymphotropic virus type 1 (HTLV-1) infection and transformation

PubMed Central

Lairmore, Michael D; Silverman, Lee; Ratner, Lee

2009-01-01

Over the past 25 years, animal models of human T-lymphotropic virus type 1 (HTLV-1) infection and transformation have provided critical knowledge about viral and host factors in adult T-cell leukemia/lymphoma (ATL). The virus consistently infects rabbits, some non-human primates, and to a lesser extent rats. In addition to providing fundamental concepts in viral transmission and immune responses against HTLV-1 infection, these models have provided new information about the role of viral proteins in carcinogenesis. Mice and rats, in particular immunodeficient strains, are useful models to assess immunologic parameters mediating tumor outgrowth and therapeutic invention strategies against lymphoma. Genetically altered mice including both transgenic and knockout mice offer important models to test the role of specific viral and host genes in the development of HTLV-1-associated lymphoma. Novel approaches in genetic manipulation of both HTLV-1 and animal models are available to address the complex questions that remain about viral-mediated mechanisms of cell transformation and disease. Current progress in the understanding of the molecular events of HTLV-1 infection and transformation suggests that answers to these questions are approachable using animal models of HTLV-1-associated lymphoma PMID:16155607

Isometric Mid-Thigh Pull Correlates With Strength, Sprint, and Agility Performance in Collegiate Rugby Union Players.

PubMed

Wang, Ran; Hoffman, Jay R; Tanigawa, Satoru; Miramonti, Amelia A; La Monica, Michael B; Beyer, Kyle S; Church, David D; Fukuda, David H; Stout, Jeffrey R

2016-11-01

Wang, R, Hoffman, JR, Tanigawa, S, Miramonti, AA, La Monica, MB, Beyer, KS, Church, DD, Fukuda, DH, and Stout, JR. Isometric mid-thigh pull correlates with strength, sprint, and agility performance in collegiate rugby union players. J Strength Cond Res 30(11): 3051-3056, 2016-The purpose of this investigation was to examine the relationships between isometric mid-thigh pull (IMTP) force and strength, sprint, and agility performance in collegiate rugby union players. Fifteen members of a champion-level university's club rugby union team (mean ± SD: 20.67 ± 1.23 years, 1.78 ± 0.06 m, and 86.51 ± 14.18 kg) participated in this investigation. One repetition maximum (1RM) squat, IMTP, speed (40 m sprint), and agility (proagility test and T-test) were performed during 3 separate testing sessions. Rate of force development (RFD) and force output at 30, 50, 90, 100, 150, 200, and 250 milliseconds of IMTP, as well as the peak value were determined. Pearson product-moment correlation analysis was used to examine the relationships between these measures. Performance in the 1RM squat was significantly correlated to the RFD between 90 and 250 milliseconds from the start of contraction (r's ranging from 0.595 to 0.748), and peak force (r = 0.866, p ≤ 0.05). One repetition maximum squat was also correlated to force outputs between 90 and 250 milliseconds (r's ranging from 0.757 to 0.816, p ≤ 0.05). Sprint time over the first 5 m in the 40 m sprint was significantly (p ≤ 0.05) correlated with peak RFD (r = -0.539) and RFD between 30 and 50 milliseconds (r's = -0.570 and -0.527, respectively). Time for the proagility test was correlated with peak RFD (r = -0.523, p ≤ 0.05) and RFD between 30 and 100 milliseconds (r's ranging from -0.518 to -0.528, p's < 0.05). Results of this investigation indicate that IMTP variables are significantly associated with strength, agility, and sprint performance. Future studies should examine IMTP as a potential tool to monitor athletic

Differences in Physicochemical and Nutritional Properties of Breast and Thigh Meat from Crossbred Chickens, Commercial Broilers, and Spent Hens

PubMed Central

Chen, Yulian; Qiao, Yan; Xiao, Yu; Chen, Haochun; Zhao, Liang; Huang, Ming; Zhou, Guanghong

2016-01-01

The objective of this study was to compare the physicochemical and nutritional properties of breast and thigh meat from commercial Chinese crossbred chickens (817 Crossbred chicken, 817C), imported commercial broilers (Arbor Acres broiler, AAB), and commercial spent hens (Hyline Brown, HLB). The crossbred chickens, commercial broilers and spent hens were slaughtered at their typical market ages of 45 d, 40 d, and 560 d, respectively. The results revealed that several different characteristic features for the three breeds. The meat of the 817C was darker than that of the other two genotypes. The 817C were also characterized by higher protein, lower intramuscular fat, and better texture attributes (cooking loss, pressing loss and Warner-Bratzler shear force [WBSF]) compared with AAB and HLB. The meat of the spent hens (i.e. HLB) was higher in WBSF and total collagen content than meat of the crossbred chickens and imported broilers. Furthermore, correlation analysis and principal component analysis revealed that there was a clear relationship among physicochemical properties of chicken meats. With regard to nutritional properties, it was found that 817C and HLB exhibited higher contents of essential amino acids and essential/non-essential amino acid ratios. In addition, 817C were noted to have highest content of microelements whereas AAB have highest content of potassium. Besides, 817C birds had particularly higher proportions of desirable fatty acids, essential fatty acids, polyunsaturated/saturated and (18:0+18:1)/16:0 ratios. The present study also revealed that there were significant differences on breast meat and thigh meat for the physicochemical and nutritional properties, regardless of chicken breeds. In conclusion, meat of crossbred chickens has some unique features and exhibited more advantages over commercial broilers and spent hens. Therefore, the current investigation would provide valuable information for the chicken meat product processing, and

Differences in Physicochemical and Nutritional Properties of Breast and Thigh Meat from Crossbred Chickens, Commercial Broilers, and Spent Hens.

PubMed

Chen, Yulian; Qiao, Yan; Xiao, Yu; Chen, Haochun; Zhao, Liang; Huang, Ming; Zhou, Guanghong

2016-06-01

The objective of this study was to compare the physicochemical and nutritional properties of breast and thigh meat from commercial Chinese crossbred chickens (817 Crossbred chicken, 817C), imported commercial broilers (Arbor Acres broiler, AAB), and commercial spent hens (Hyline Brown, HLB). The crossbred chickens, commercial broilers and spent hens were slaughtered at their typical market ages of 45 d, 40 d, and 560 d, respectively. The results revealed that several different characteristic features for the three breeds. The meat of the 817C was darker than that of the other two genotypes. The 817C were also characterized by higher protein, lower intramuscular fat, and better texture attributes (cooking loss, pressing loss and Warner-Bratzler shear force [WBSF]) compared with AAB and HLB. The meat of the spent hens (i.e. HLB) was higher in WBSF and total collagen content than meat of the crossbred chickens and imported broilers. Furthermore, correlation analysis and principal component analysis revealed that there was a clear relationship among physicochemical properties of chicken meats. With regard to nutritional properties, it was found that 817C and HLB exhibited higher contents of essential amino acids and essential/non-essential amino acid ratios. In addition, 817C were noted to have highest content of microelements whereas AAB have highest content of potassium. Besides, 817C birds had particularly higher proportions of desirable fatty acids, essential fatty acids, polyunsaturated/saturated and (18:0+18:1)/16:0 ratios. The present study also revealed that there were significant differences on breast meat and thigh meat for the physicochemical and nutritional properties, regardless of chicken breeds. In conclusion, meat of crossbred chickens has some unique features and exhibited more advantages over commercial broilers and spent hens. Therefore, the current investigation would provide valuable information for the chicken meat product processing, and

Efficacy of bacteriophage therapy in a model of Burkholderia cenocepacia pulmonary infection

PubMed Central

Carmody, Lisa A.; Gill, Jason J.; Summer, Elizabeth J.; Sajjan, Uma S.; Gonzalez, Carlos F.; Young, Ryland F.; LiPuma, John J.

2009-01-01

The therapeutic potential of bacteriophage (phage) in a mouse model of acute B. cenocepacia pulmonary infection was assessed. Phage were administered by either intranasal (i.n.) inhalation or intraperitoneal (i.p.) injection. Bacterial density, macrophage inflammatory protein-2 (MIP-2), and tumor necrosis factor-α (TNFα) levels were significantly reduced in lungs of mice treated with i.p. phage. No significant differences in lung bacterial density or MIP-2 levels were found between untreated mice and mice treated with i.n. phage, i.p. UV-inactivated phage, or i.p. λ phage controls. Mock-infected mice treated with phage showed no significant increase in lung MIP-2 or TNFα levels compared to mock-infected / mock-treated mice. We have demonstrated the efficacy of phage therapy in an acute B. cenocepacia lung infection model. Systemic administration of phage was more effective than inhalational administration, suggesting that circulating phage have better access to bacteria in lung compared to topical phage. PMID:20001604

Development and Validation of a Weather-Based Model for Predicting Infection of Loquat Fruit by Fusicladium eriobotryae

PubMed Central

González-Domínguez, Elisa; Armengol, Josep; Rossi, Vittorio

2014-01-01

A mechanistic, dynamic model was developed to predict infection of loquat fruit by conidia of Fusicladium eriobotryae, the causal agent of loquat scab. The model simulates scab infection periods and their severity through the sub-processes of spore dispersal, infection, and latency (i.e., the state variables); change from one state to the following one depends on environmental conditions and on processes described by mathematical equations. Equations were developed using published data on F. eriobotryae mycelium growth, conidial germination, infection, and conidial dispersion pattern. The model was then validated by comparing model output with three independent data sets. The model accurately predicts the occurrence and severity of infection periods as well as the progress of loquat scab incidence on fruit (with concordance correlation coefficients >0.95). Model output agreed with expert assessment of the disease severity in seven loquat-growing seasons. Use of the model for scheduling fungicide applications in loquat orchards may help optimise scab management and reduce fungicide applications. PMID:25233340

HIV model incorporating differential progression for treatment-naive and treatment-experienced infectives.

PubMed

Chigidi, Esther; Lungu, Edward M

2009-07-01

We formulate an HIV/AIDS deterministic model which incorporates differential infectivity and disease progression for treatment-naive and treatment-experienced HIV/AIDS infectives. To illustrate our model, we have applied it to estimate adult HIV prevalence, the HIV population, the number of new infectives and the number of AIDS deaths for Botswana for the period 1984 to 2012. It is found that the prevalence peaked in the year 2000 and the HIV population is now decreasing. We have also found that under the current conditions, the reproduction number is Rc approximately 13, which is less than the 2004 estimate of Rc approximately equal 4 by [11] and [13]. The results in this study suggest that the HAART program has yielded positive results for Botswana.

Interval Between Infections and Viral Hierarchy Are Determinants of Viral Interference Following Influenza Virus Infection in a Ferret Model

PubMed Central

Laurie, Karen L.; Guarnaccia, Teagan A.; Carolan, Louise A.; Yan, Ada W. C.; Aban, Malet; Petrie, Stephen; Cao, Pengxing; Heffernan, Jane M.; McVernon, Jodie; Mosse, Jennifer; Kelso, Anne; McCaw, James M.; Barr, Ian G.

2015-01-01

Background. Epidemiological studies suggest that, following infection with influenza virus, there is a short period during which a host experiences a lower susceptibility to infection with other influenza viruses. This viral interference appears to be independent of any antigenic similarities between the viruses. We used the ferret model of human influenza to systematically investigate viral interference. Methods. Ferrets were first infected then challenged 1–14 days later with pairs of influenza A(H1N1)pdm09, influenza A(H3N2), and influenza B viruses circulating in 2009 and 2010. Results. Viral interference was observed when the interval between initiation of primary infection and subsequent challenge was <1 week. This effect was virus specific and occurred between antigenically related and unrelated viruses. Coinfections occurred when 1 or 3 days separated infections. Ongoing shedding from the primary virus infection was associated with viral interference after the secondary challenge. Conclusions. The interval between infections and the sequential combination of viruses were important determinants of viral interference. The influenza viruses in this study appear to have an ordered hierarchy according to their ability to block or delay infection, which may contribute to the dominance of different viruses often seen in an influenza season. PMID:25943206

Analysis of Endothelial Adherence of Bartonella henselae and Acinetobacter baumannii Using a Dynamic Human Ex Vivo Infection Model

PubMed Central

Weidensdorfer, Marko; Chae, Ju Ik; Makobe, Celestine; Stahl, Julia; Averhoff, Beate; Müller, Volker; Schürmann, Christoph; Brandes, Ralf P.; Wilharm, Gottfried; Ballhorn, Wibke; Christ, Sara; Linke, Dirk; Fischer, Doris; Göttig, Stephan

2015-01-01

Bacterial adherence determines the virulence of many human-pathogenic bacteria. Experimental approaches elucidating this early infection event in greater detail have been performed using mainly methods of cellular microbiology. However, in vitro infections of cell monolayers reflect the in vivo situation only partially, and animal infection models are not available for many human-pathogenic bacteria. Therefore, ex vivo infection of human organs might represent an attractive method to overcome these limitations. We infected whole human umbilical cords ex vivo with Bartonella henselae or Acinetobacter baumannii under dynamic flow conditions mimicking the in vivo infection situation of human endothelium. For this purpose, methods for quantifying endothelium-adherent wild-type and trimeric autotransporter adhesin (TAA)-deficient bacteria were set up. Data revealed that (i) A. baumannii binds in a TAA-dependent manner to endothelial cells, (ii) this organ infection model led to highly reproducible adherence rates, and furthermore, (iii) this model allowed to dissect the biological function of TAAs in the natural course of human infections. These findings indicate that infection models using ex vivo human tissue samples (“organ microbiology”) might be a valuable tool in analyzing bacterial pathogenicity with the capacity to replace animal infection models at least partially. PMID:26712205

Validation of a Novel Murine Wound Model of Acinetobacter baumannii Infection

PubMed Central

Thompson, Mitchell G.; Black, Chad C.; Pavlicek, Rebecca L.; Honnold, Cary L.; Wise, Matthew C.; Alamneh, Yonas A.; Moon, Jay K.; Kessler, Jennifer L.; Si, Yuanzheng; Williams, Robert; Yildirim, Suleyman; Kirkup, Benjamin C.; Green, Romanza K.; Hall, Eric R.; Palys, Thomas J.

2014-01-01

Patients recovering from traumatic injuries or surgery often require weeks to months of hospitalization, increasing the risk for wound and surgical site infections caused by ESKAPE pathogens, which include A. baumannii (the ESKAPE pathogens are Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). As new therapies are being developed to counter A. baumannii infections, animal models are also needed to evaluate potential treatments. Here, we present an excisional, murine wound model in which a diminutive inoculum of a clinically relevant, multidrug-resistant A. baumannii isolate can proliferate, form biofilms, and be effectively treated with antibiotics. The model requires a temporary, cyclophosphamide-induced neutropenia to establish an infection that can persist. A 6-mm-diameter, full-thickness wound was created in the skin overlying the thoracic spine, and after the wound bed was inoculated, it was covered with a dressing for 7 days. Uninoculated control wounds healed within 13 days, whereas infected, placebo-treated wounds remained unclosed beyond 21 days. Treated and untreated wounds were assessed with multiple quantitative and qualitative techniques that included gross pathology, weight loss and recovery, wound closure, bacterial burden, 16S rRNA community profiling, histopathology, peptide nucleic acid-fluorescence in situ hybridization, and scanning electron microscopy assessment of biofilms. The range of differences that we are able to identify with these measures in antibiotic- versus placebo-treated animals provides a clear window within which novel antimicrobial therapies can be assessed. The model can be used to evaluate antimicrobials for their ability to reduce specific pathogen loads in wounded tissues and clear biofilms. Ultimately, the mouse model approach allows for highly powered studies and serves as an initial multifaceted in vivo assessment prior to

Latent Tuberculosis Infection: Myths, Models, and Molecular Mechanisms

PubMed Central

Dutta, Noton K.

2014-01-01

SUMMARY The aim of this review is to present the current state of knowledge on human latent tuberculosis infection (LTBI) based on clinical studies and observations, as well as experimental in vitro and animal models. Several key terms are defined, including “latency,” “persistence,” “dormancy,” and “antibiotic tolerance.” Dogmas prevalent in the field are critically examined based on available clinical and experimental data, including the long-held beliefs that infection is either latent or active, that LTBI represents a small population of nonreplicating, “dormant” bacilli, and that caseous granulomas are the haven for LTBI. The role of host factors, such as CD4+ and CD8+ T cells, T regulatory cells, tumor necrosis factor alpha (TNF-α), and gamma interferon (IFN-γ), in controlling TB infection is discussed. We also highlight microbial regulatory and metabolic pathways implicated in bacillary growth restriction and antibiotic tolerance under various physiologically relevant conditions. Finally, we pose several clinically important questions, which remain unanswered and will serve to stimulate future research on LTBI. PMID:25184558

The Effect of a Vegetarian vs Conventional Hypocaloric Diabetic Diet on Thigh Adipose Tissue Distribution in Subjects with Type 2 Diabetes: A Randomized Study.

PubMed

Kahleova, Hana; Klementova, Marta; Herynek, Vit; Skoch, Antonin; Herynek, Stepan; Hill, Martin; Mari, Andrea; Pelikanova, Terezie

2017-07-01

The aim of our study was to compare the effects of a vegetarian and a conventional diet on thigh adipose tissue distribution in subjects with type 2 diabetes (T2D). Seventy-four subjects with T2D were randomly assigned to either follow a vegetarian diet (V, n = 37) or a control group who followed an isocaloric conventional anti-diabetic diet (C, n = 37). Both diets were calorie restricted (-500 kcal/day). To measure insulin sensitivity, the hyperinsulinemic (1 mU.kg -1 .min -1 ) isoglycemic clamp was conducted. β-Cell function was assessed using a mathematical model after a test meal. Magnetic resonance imaging of the thigh was performed. All subjects were examined at 0, 3, and 6 months. Statistical analyses were performed using repeated measures analysis of variance and a multivariate regression model. Greater reduction was observed in total leg area in V (-13.6 cm 2 [95% confidence interval [CI], -14.2 to -12.9] in V vs -9.9 cm 2 [95% CI, -10.6 to -9.2] in C; Gxt p < 0.001). The reduction in subcutaneous fat was comparable in response to both diets (Gxt, p = 0.64). Subfascial fat was reduced only in response to a vegetarian diet (-0.82 [95% CI, -1.13 to -0.55] cm 2 in V vs -0.44 [95% CI, -0.78 to +0.02] cm 2 in C; Gxt, p = 0.04). The reduction in intramuscular fat tended to be greater in response to a vegetarian diet (-1.78 [95% CI, -2.26 to -1.27] cm 2 in V vs -0.57 [95% CI, -1.06 to -0.09] cm 2 in C; Gxt, p = 0.12). Changes in subcutaneous and subfascial fat correlated with changes in glycated hemoglobin (HbA1c), fasting plasma glucose, and β-cell insulin sensitivity. After adjustment for changes in body mass index (BMI), correlations remained significant for changes in fasting plasma glucose and β-cell insulin sensitivity and with changes in triglycerides. Our data indicate the importance of both subcutaneous and subfascial fat in relationship to glucose and lipid metabolism. BMI , body mass index; C , control group; FPG , fasting plasma glucose; Gxt

Mathematical Modeling of the Dynamics of Salmonella Cerro Infection in a US Dairy Herd

NASA Astrophysics Data System (ADS)

Chapagain, Prem; van Kessel, Jo Ann; Karns, Jeffrey; Wolfgang, David; Schukken, Ynte; Grohn, Yrjo

2006-03-01

Salmonellosis has been one of the major causes of human foodborne illness in the US. The high prevalence of infections makes transmission dynamics of Salmonella in a farm environment of interest both from animal and human health perspectives. Mathematical modeling approaches are increasingly being applied to understand the dynamics of various infectious diseases in dairy herds. Here, we describe the transmission dynamics of Salmonella infection in a dairy herd with a set of non-linear differential equations. Although the infection dynamics of different serotypes of Salmonella in cattle are likely to be different, we find that a relatively simple SIR-type model can describe the observed dynamics of the Salmonella enterica serotype Cerro infection in the herd.

Protection from genital herpes disease, seroconversion and latent infection in a non-lethal murine genital infection model by immunization with an HSV-2 replication-defective mutant virus.

PubMed

Diaz, Fernando M; Knipe, David M

2016-01-15

Viral vaccines have traditionally protected against disease, but for viruses that establish latent infection, it is desirable for the vaccine to reduce infection to reduce latent infection and reactivation. While seroconversion has been used in clinical trials of herpes simplex virus (HSV) vaccines to measure protection from infection, this has not been modeled in animal infection systems. To measure the ability of a genital herpes vaccine candidate to protect against various aspects of infection, we established a non-lethal murine model of genital HSV-2 infection, an ELISA assay to measure antibodies specific for infected cell protein 8 (ICP8), and a very sensitive qPCR assay. Using these assays, we observed that immunization with HSV-2 dl5-29 virus reduced disease, viral shedding, seroconversion, and latent infection by the HSV-2 challenge virus. Therefore, it may be feasible to obtain protection against genital disease, seroconversion and latent infection by immunization, even if sterilizing immunity is not achieved. Copyright © 2015 Elsevier Inc. All rights reserved.

On cell resistance and immune response time lag in a model for the HIV infection

NASA Astrophysics Data System (ADS)

Solovey, Guillermo; Peruani, Fernando; Ponce Dawson, Silvina; Maria Zorzenon dos Santos, Rita

2004-11-01

Recently, a cellular automata model has been introduced (Phys. Rev. Lett. 87 (2001) 168102) to describe the spread of the HIV infection among target cells in lymphoid tissues. The model reproduces qualitatively the entire course of the infection displaying, in particular, the two time scales that characterize its dynamics. In this work, we investigate the robustness of the model against changes in three of its parameters. Two of them are related to the resistance of the cells to get infected. The other one describes the time interval necessary to mount specific immune responses. We have observed that an increase of the cell resistance, at any stage of the infection, leads to a reduction of the latency period, i.e., of the time interval between the primary infection and the onset of AIDS. However, during the early stages of the infection, when the cell resistance increase is combined with an increase in the initial concentration of infected cells, the original behavior is recovered. Therefore we find a long and a short latency regime (eight and one year long, respectively) depending on the value of the cell resistance. We have obtained, on the other hand, that changes on the parameter that describes the immune system time lag affects the time interval during which the primary infection occurs. Using different extended versions of the model, we also discuss how the two-time scale dynamics is affected when we include inhomogeneities on the cells properties, as for instance, on the cell resistance or on the time interval to mount specific immune responses.

A review of telavancin activity in in vitro biofilms and animal models of biofilm-associated infections.

PubMed

Chan, Cynthia; Hardin, Thomas C; Smart, Jennifer I

2015-01-01

Tissue- and device-associated biofilm infections are important medical problems. These infections are difficult to treat due to a high-level of tolerance to antibiotics. Telavancin has been studied in several in vitro biofilm models and has demonstrated efficacy against staphylococcal and enterococcal-associated biofilm infections, including those formed by methicillin-resistant Staphylococcus aureus. Telavancin was effective against the difficult-to-treat vancomycin- and glycopeptide-intermediate strains of S. aureus in these models. Furthermore, the efficacy of telavancin has been evaluated in several biofilm-related in vivo models, including osteomyelitis, endocarditis and device-associated infections in rabbits. Overall, telavancin exhibited similar or greater efficacy than vancomycin and other comparators in these animal models and maintained activity against vancomycin-intermediate and daptomycin nonsusceptible strains of S. aureus.

Quantitative detection of Toxoplasma gondii in tissues of experimentally infected turkeys and in retail turkey products by magnetic-capture PCR.

PubMed

Koethe, Martin; Straubinger, Reinhard K; Pott, Susan; Bangoura, Berit; Geuthner, Anne-Catrin; Daugschies, Arwid; Ludewig, Martina

2015-12-01

Magnetic-capture PCR was applied for the quantitative detection of Toxoplasma gondii in tissues of experimentally infected turkeys and retail turkey meat products. For experimental infection, three T. gondii strains (ME49, CZ-Tiger, NED), varying infectious doses in different matrices (organisms in single mouse brains or 10(3), 10(5), or 10(6) oocysts in buffer) were used. From all animals, breast, thigh, and drumstick muscle tissues and for CZ-Tiger-infected animals additionally brains and hearts were analyzed. Using the magnetic-capture PCR large volumes of up to 100 g were examined. Our results show that most T. gondii parasites are present in brain and heart tissue. Of the three skeletal muscle types, drumsticks were affected at the highest and breast at the lowest level. Type III strain (NED) seems to be less efficient in infecting turkeys compared to type II strains, because only few tissues of NED infected animals contained T. gondii DNA. Furthermore, the number of detected parasitic stages increased with the level of infectious dose. Infection mode by either oocyst or tissue cyst stage did not have an effect on the amount of T. gondii present in tissues. In retail turkey meat products T. gondii DNA was not detectable although a contact with the parasite was inferred by serology. Copyright © 2015 Elsevier Ltd. All rights reserved.

Discrete Dynamical Modeling of Influenza Virus Infection Suggests Age-Dependent Differences in Immunity.

PubMed

Keef, Ericka; Zhang, Li Ang; Swigon, David; Urbano, Alisa; Ermentrout, G Bard; Matuszewski, Michael; Toapanta, Franklin R; Ross, Ted M; Parker, Robert S; Clermont, Gilles

2017-12-01

Immunosenescence, an age-related decline in immune function, is a major contributor to morbidity and mortality in the elderly. Older hosts exhibit a delayed onset of immunity and prolonged inflammation after an infection, leading to excess damage and a greater likelihood of death. Our study applies a rule-based model to infer which components of the immune response are most changed in an aged host. Two groups of BALB/c mice (aged 12 to 16 weeks and 72 to 76 weeks) were infected with 2 inocula: a survivable dose of 50 PFU and a lethal dose of 500 PFU. Data were measured at 10 points over 19 days in the sublethal case and at 6 points over 7 days in the lethal case, after which all mice had died. Data varied primarily in the onset of immunity, particularly the inflammatory response, which led to a 2-day delay in the clearance of the virus from older hosts in the sublethal cohort. We developed a Boolean model to describe the interactions between the virus and 21 immune components, including cells, chemokines, and cytokines, of innate and adaptive immunity. The model identifies distinct sets of rules for each age group by using Boolean operators to describe the complex series of interactions that activate and deactivate immune components. Our model accurately simulates the immune responses of mice of both ages and with both inocula included in the data (95% accurate for younger mice and 94% accurate for older mice) and shows distinct rule choices for the innate immunity arm of the model between younger and aging mice in response to influenza A virus infection. IMPORTANCE Influenza virus infection causes high morbidity and mortality rates every year, especially in the elderly. The elderly tend to have a delayed onset of many immune responses as well as prolonged inflammatory responses, leading to an overall weakened response to infection. Many of the details of immune mechanisms that change with age are currently not well understood. We present a rule-based model of the

Development of a Mouse Model of Helicobacter pylori Infection that Mimics Human Disease

NASA Astrophysics Data System (ADS)

Marchetti, Marta; Arico, Beatrice; Burroni, Daniela; Figura, Natale; Rappuoli, Rino; Ghiara, Paolo

1995-03-01

The human pathogen Helicobacter pylori is associated with gastritis, peptic ulcer disease, and gastric cancer. The pathogenesis of H. pylori infection in vivo was studied by adapting fresh clinical isolates of bacteria to colonize the stomachs of mice. A gastric pathology resembling human disease was observed in infections with cytotoxin-producing strains but not with noncytotoxic strains. Oral immunization with purified H. pylori antigens protected mice from bacterial infection. This mouse model will allow the development of therapeutic agents and vaccines against H. pylori infection in humans.

Identification of infection- and defense-related genes via a dynamic host-pathogen interaction network using a Candida albicans-zebrafish infection model.

PubMed

Kuo, Zong-Yu; Chuang, Yung-Jen; Chao, Chun-Cheih; Liu, Fu-Chen; Lan, Chung-Yu; Chen, Bor-Sen

2013-01-01

Candida albicans infections and candidiasis are difficult to treat and create very serious therapeutic challenges. In this study, based on interactive time profile microarray data of C. albicans and zebrafish during infection, the infection-related protein-protein interaction (PPI) networks of the two species and the intercellular PPI network between host and pathogen were simultaneously constructed by a dynamic interaction model, modeled as an integrated network consisting of intercellular invasion and cellular defense processes during infection. The signal transduction pathways in regulating morphogenesis and hyphal growth of C. albicans were further investigated based on significant interactions found in the intercellular PPI network. Two cellular networks were also developed corresponding to the different infection stages (adhesion and invasion), and then compared with each other to identify proteins from which we can gain more insight into the pathogenic role of hyphal development in the C. albicans infection process. Important defense-related proteins in zebrafish were predicted using the same approach. The hyphal growth PPI network, zebrafish PPI network and host-pathogen intercellular PPI network were combined to form an integrated infectious PPI network that helps us understand the systematic mechanisms underlying the pathogenicity of C. albicans and the immune response of the host, and may help improve medical therapies and facilitate the development of new antifungal drugs. Copyright © 2013 S. Karger AG, Basel.

Multiplicity of Mathematical Modeling Strategies to Search for Molecular and Cellular Insights into Bacteria Lung Infection

PubMed Central

Cantone, Martina; Santos, Guido; Wentker, Pia; Lai, Xin; Vera, Julio

2017-01-01

Even today two bacterial lung infections, namely pneumonia and tuberculosis, are among the 10 most frequent causes of death worldwide. These infections still lack effective treatments in many developing countries and in immunocompromised populations like infants, elderly people and transplanted patients. The interaction between bacteria and the host is a complex system of interlinked intercellular and the intracellular processes, enriched in regulatory structures like positive and negative feedback loops. Severe pathological condition can emerge when the immune system of the host fails to neutralize the infection. This failure can result in systemic spreading of pathogens or overwhelming immune response followed by a systemic inflammatory response. Mathematical modeling is a promising tool to dissect the complexity underlying pathogenesis of bacterial lung infection at the molecular, cellular and tissue levels, and also at the interfaces among levels. In this article, we introduce mathematical and computational modeling frameworks that can be used for investigating molecular and cellular mechanisms underlying bacterial lung infection. Then, we compile and discuss published results on the modeling of regulatory pathways and cell populations relevant for lung infection and inflammation. Finally, we discuss how to make use of this multiplicity of modeling approaches to open new avenues in the search of the molecular and cellular mechanisms underlying bacterial infection in the lung. PMID:28912729

Multiplicity of Mathematical Modeling Strategies to Search for Molecular and Cellular Insights into Bacteria Lung Infection.

PubMed

Cantone, Martina; Santos, Guido; Wentker, Pia; Lai, Xin; Vera, Julio

2017-01-01

Even today two bacterial lung infections, namely pneumonia and tuberculosis, are among the 10 most frequent causes of death worldwide. These infections still lack effective treatments in many developing countries and in immunocompromised populations like infants, elderly people and transplanted patients. The interaction between bacteria and the host is a complex system of interlinked intercellular and the intracellular processes, enriched in regulatory structures like positive and negative feedback loops. Severe pathological condition can emerge when the immune system of the host fails to neutralize the infection. This failure can result in systemic spreading of pathogens or overwhelming immune response followed by a systemic inflammatory response. Mathematical modeling is a promising tool to dissect the complexity underlying pathogenesis of bacterial lung infection at the molecular, cellular and tissue levels, and also at the interfaces among levels. In this article, we introduce mathematical and computational modeling frameworks that can be used for investigating molecular and cellular mechanisms underlying bacterial lung infection. Then, we compile and discuss published results on the modeling of regulatory pathways and cell populations relevant for lung infection and inflammation. Finally, we discuss how to make use of this multiplicity of modeling approaches to open new avenues in the search of the molecular and cellular mechanisms underlying bacterial infection in the lung.

Animal models for Ebola and Marburg virus infections

PubMed Central

Nakayama, Eri; Saijo, Masayuki

2013-01-01

Ebola and Marburg hemorrhagic fevers (EHF and MHF) are caused by the Filoviridae family, Ebolavirus and Marburgvirus (ebolavirus and marburgvirus), respectively. These severe diseases have high mortality rates in humans. Although EHF and MHF are endemic to sub-Saharan Africa. A novel filovirus, Lloviu virus, which is genetically distinct from ebolavirus and marburgvirus, was recently discovered in Spain where filoviral hemorrhagic fever had never been reported. The virulence of this virus has not been determined. Ebolavirus and marburgvirus are classified as biosafety level-4 (BSL-4) pathogens and Category A agents, for which the US government requires preparedness in case of bioterrorism. Therefore, preventive measures against these viral hemorrhagic fevers should be prepared, not only in disease-endemic regions, but also in disease-free countries. Diagnostics, vaccines, and therapeutics need to be developed, and therefore the establishment of animal models for EHF and MHF is invaluable. Several animal models have been developed for EHF and MHF using non-human primates (NHPs) and rodents, which are crucial to understand pathophysiology and to develop diagnostics, vaccines, and therapeutics. Rhesus and cynomolgus macaques are representative models of filovirus infection as they exhibit remarkably similar symptoms to those observed in humans. However, the NHP models have practical and ethical problems that limit their experimental use. Furthermore, there are no inbred and genetically manipulated strains of NHP. Rodent models such as mouse, guinea pig, and hamster, have also been developed. However, these rodent models require adaptation of the virus to produce lethal disease and do not mirror all symptoms of human filovirus infection. This review article provides an outline of the clinical features of EHF and MHF in animals, including humans, and discusses how the animal models have been developed to study pathophysiology, vaccines, and therapeutics. PMID:24046765

Animal models for Ebola and Marburg virus infections.

PubMed

Nakayama, Eri; Saijo, Masayuki

2013-09-05

Ebola and Marburg hemorrhagic fevers (EHF and MHF) are caused by the Filoviridae family, Ebolavirus and Marburgvirus (ebolavirus and marburgvirus), respectively. These severe diseases have high mortality rates in humans. Although EHF and MHF are endemic to sub-Saharan Africa. A novel filovirus, Lloviu virus, which is genetically distinct from ebolavirus and marburgvirus, was recently discovered in Spain where filoviral hemorrhagic fever had never been reported. The virulence of this virus has not been determined. Ebolavirus and marburgvirus are classified as biosafety level-4 (BSL-4) pathogens and Category A agents, for which the US government requires preparedness in case of bioterrorism. Therefore, preventive measures against these viral hemorrhagic fevers should be prepared, not only in disease-endemic regions, but also in disease-free countries. Diagnostics, vaccines, and therapeutics need to be developed, and therefore the establishment of animal models for EHF and MHF is invaluable. Several animal models have been developed for EHF and MHF using non-human primates (NHPs) and rodents, which are crucial to understand pathophysiology and to develop diagnostics, vaccines, and therapeutics. Rhesus and cynomolgus macaques are representative models of filovirus infection as they exhibit remarkably similar symptoms to those observed in humans. However, the NHP models have practical and ethical problems that limit their experimental use. Furthermore, there are no inbred and genetically manipulated strains of NHP. Rodent models such as mouse, guinea pig, and hamster, have also been developed. However, these rodent models require adaptation of the virus to produce lethal disease and do not mirror all symptoms of human filovirus infection. This review article provides an outline of the clinical features of EHF and MHF in animals, including humans, and discusses how the animal models have been developed to study pathophysiology, vaccines, and therapeutics.

Development of Novel Antibiotic Lysocin E Identified by Silkworm Infection Model.

PubMed

Hamamoto, Hiroshi; Sekimizu, Kazuhisa

2017-01-01

In this symposium, we reported the identification and mechanistic analysis of a novel antibiotic named lysocin E. Lysocin E was identified by screening for therapeutic effectiveness in a silkworm Staphylococcus aureus infection model. The advantages of the silkworm infection model for screening and purification of antibiotics from the culture supernatant of soil bacteria are: 1) low cost; 2) no ethical issues; 3) convenient for evaluation of the therapeutic effectiveness of antibiotics; and 4) pharmacokinetics similar to those of mammals. Lysocin E has remarkable features compared with known antibiotics such as a novel mechanism of action and target. Here, we summarize our reports presented in this symposium.

The chicken as a natural model for extraintestinal infections caused by avian pathogenic Escherichia coli (APEC).

PubMed

Antão, Esther-Maria; Glodde, Susanne; Li, Ganwu; Sharifi, Reza; Homeier, Timo; Laturnus, Claudia; Diehl, Ines; Bethe, Astrid; Philipp, Hans-C; Preisinger, Rudolf; Wieler, Lothar H; Ewers, Christa

2008-01-01

E. coli infections in avian species have become an economic threat to the poultry industry worldwide. Several factors have been associated with the virulence of E. coli in avian hosts, but no specific virulence gene has been identified as being entirely responsible for the pathogenicity of avian pathogenic E. coli (APEC). Needless to say, the chicken would serve as the best model organism for unravelling the pathogenic mechanisms of APEC, an extraintestinal pathogen. Five-week-old white leghorn SPF chickens were infected intra-tracheally with a well characterized APEC field strain IMT5155 (O2:K1:H5) using different doses corresponding to the respective models of infection established, that is, the lung colonization model allowing re-isolation of bacteria only from the lung but not from other internal organs, and the systemic infection model. These two models represent the crucial steps in the pathogenesis of APEC infections, including the colonization of the lung epithelium and the spread of bacteria throughout the bloodstream. The read-out system includes a clinical score, pathomorphological changes and bacterial load determination. The lung colonization model has been established and described for the first time in this study, in addition to a comprehensive account of a systemic infection model which enables the study of severe extraintestinal pathogenic E. coli (ExPEC) infections. These in vivo models enable the application of various molecular approaches to study host-pathogen interactions more closely. The most important application of such genetic manipulation techniques is the identification of genes required for extraintestinal virulence, as well as host genes involved in immunity in vivo. The knowledge obtained from these studies serves the dual purpose of shedding light on the nature of virulence itself, as well as providing a route for rational attenuation of the pathogen for vaccine construction, a measure by which extraintestinal infections, including

[Repair of pressure sores over ischial tuberosity with long head of biceps femoris muscle flap combined with semi-V posterior thigh fasciocutaneous flap].

PubMed

Hai, Heng-lin; Shen, Chuan-an; Chai, Jia-ke; Li, Hua-tao

2012-02-01

To explore the clinical effect of transplantation of the long head of biceps femoris muscle flap in combination with semi-V posterior thigh fasciocutaneous flap for repair of pressure sores over ischial tuberosity. Eight patients with 10 deep pressure sores over ischial tuberosity were admitted to the First Affiliated Hospital to the PLA General Hospital and the 98th Hospital of PLA from April 2004 to June 2010. The wounds measured from 2 cm × 2 cm to 6 cm × 4 cm were covered with the long head of biceps femoris muscle flap and semi-V posterior thigh fasciocutaneous flap (ranged from 10 cm × 6 cm to 13 cm × 8 cm). The condition of flaps was observed and followed up for a long time. All flaps survived. Nine wounds healed by first intention. Subcutaneous accumulation of fluids occurred in one wound with formation of a sinus at drainage site, and it healed after dressing change for 25 days. Patients were followed up for 7 to 34 months. Sore recurred in one patient 9 months after surgery, and it was successfully repaired with the same flap for the second time. Flaps in the other 7 patients appeared satisfactory with soft texture and without ulceration. This combined flap is easy in formation and transfer, and it causes little side injury with good resistance against pressure. It is a new method for repair of pressure sore over sacral region.

Testing the Quality Health Outcomes Model Applied to Infection Prevention in Hospitals.

PubMed

Gilmartin, Heather M; Sousa, Karen H

2016-01-01

To test the Quality Health Outcomes Model to investigate the relationship between health care-associated infection (HAI) prevention interventions, organizational context, and HAI outcomes using structural equation modeling. Variables for adherence to the central line bundle, organizational context, and central line-associated bloodstream infections (CLABSIs) were selected for this secondary data analysis from 614 US hospitals that participated in the Prevention of Nosocomial Infection and Cost-effectiveness-Refined study. One half of the dataset was used for exploration of the concepts, the second half for confirmation of the measurement models and testing of the structural model. The final model resulted in a good fit to the data (χ (1215) = 1906.86, P < .00; comparative fit index = 0.94; root mean square of error of approximation = 0.04). A significant relationship was noted between adherence to the central line bundle interventions and organizational context (β = 0.23, P < .01), whereas the relationship between context and CLABSIs was not significant (β = -0.20, P = .78). This study supports a relationship between greater adherence to HAI interventions and higher levels of organizational context and highlights the complexity of measuring organizational context. Given the importance of preventing HAIs, ongoing research is needed to reveal the exact aspects of context that influence interventions and outcomes.

Automated assessment of thigh composition using machine learning for Dixon magnetic resonance images.

PubMed

Yang, Yu Xin; Chong, Mei Sian; Tay, Laura; Yew, Suzanne; Yeo, Audrey; Tan, Cher Heng

2016-10-01

To develop and validate a machine learning based automated segmentation method that jointly analyzes the four contrasts provided by Dixon MRI technique for improved thigh composition segmentation accuracy. The automatic detection of body composition is formulized as a three-class classification issue. Each image voxel in the training dataset is assigned with a correct label. A voxel classifier is trained and subsequently used to predict unseen data. Morphological operations are finally applied to generate volumetric segmented images for different structures. We applied this algorithm on datasets of (1) four contrast images, (2) water and fat images, and (3) unsuppressed images acquired from 190 subjects. The proposed method using four contrasts achieved most accurate and robust segmentation compared to the use of combined fat and water images and the use of unsuppressed image, average Dice coefficients of 0.94 ± 0.03, 0.96 ± 0.03, 0.80 ± 0.03, and 0.97 ± 0.01 has been achieved to bone region, subcutaneous adipose tissue (SAT), inter-muscular adipose tissue (IMAT), and muscle respectively. Our proposed method based on machine learning produces accurate tissue quantification and showed an effective use of large information provided by the four contrast images from Dixon MRI.

Use of anteromedial thigh perforator flap and immunological implications of Gorlin-Goltz syndrome: a case study.

PubMed

Scalise, A; Calamita, R; Tartaglione, C; Bolletta, E; Di Benedetto, G; Pierangeli, M

2016-12-02

Gorlin-Goltz syndrome is mainly characterised by the development of numerous multicentric and relapsing cutaneous basal cell carcinomas (BCCs). A major problem for patients with Gorlin-Goltz syndrome is the large amount of BCCs that can invade the deep underlying structures, especially the face. Here, we describe the case of a 23-year-old male affected by Gorlin-Goltz syndrome. He had recurrent BCCs on a hairless scalp and dorsum since he was 17 years old and underwent four surgical procedures to excise BCCs, including a reconstruction with anteromedial thigh perforator flap. For each of the surgical procedures, a phenotypic study on peripheral blood mononuclear cells using flow cytometry was performed on the same day of surgery, and on days 7, 14 and 21 after surgery. The role of the tumour-specific cytolytic immune response as a potential future treatment of syndromic BCCs and its trend in relation to surgical ablation of large portions of tumour tissue was examined, and the cosmetic and therapeutic results are shown.

Effects of milk product intake on thigh muscle strength and NFKB gene methylation during home-based interval walking training in older women: A randomized, controlled pilot study

PubMed Central

Masuki, Shizue; Nishida, Kensei; Hashimoto, Shigenari; Morikawa, Mayuko; Takasugi, Satoshi; Nagata, Masashi; Taniguchi, Shun'ichiro; Rokutan, Kazuhito

2017-01-01

Background Muscle atrophy with aging is closely associated with chronic systemic inflammation and lifestyle-related diseases. In the present study, we assessed whether post-exercise milk product intake during 5-month interval walking training (IWT) enhanced the increase in thigh muscle strength and ameliorated susceptibility to inflammation in older women. Methods Subjects [n = 37, 66±5 (standard deviation) yrs] who had been performing IWT for >6 months participated in this study. They were randomly divided into the following 3 groups: IWT alone (CNT, n = 12), IWT + low-dose post-exercise milk product intake (LD, n = 12; 4 g protein and 3 g carbohydrate) or IWT + a 3-times higher dose of milk product intake than the LD group (HD, n = 13). They were instructed to repeat ≥5 sets of fast and slow walking for 3 min each at ≥70% and 40% peak aerobic capacity for walking, respectively, per day for ≥4 days/week. Results After IWT, thigh muscle strength increased in the HD group (8±2%) more than in the CNT group (-2±3%, P = 0.022), despite similar IWT achievements between the groups (P>0.15). Pyrosequencing analysis using whole blood showed that methylation of NFKB1 and NFKB2, master genes of inflammation, was enhanced in the HD group (29±7% and 44±11%, respectively) more than in the CNT group (-20±6% and -10±6%, respectively; P<0.001). Moreover, the genome-wide DNA methylation analysis showed that several inflammation-related genes were hyper-methylated in the HD group compared with that in the CNT group, suggesting greater pro-inflammatory cytokine gene suppression in the HD group. Conclusion HD milk product intake after exercise produced a greater percent increase in thigh muscle strength and NFKB1 and NFKB2 gene methylation during IWT in physically active older women. Trial registration UMIN-CTR No. UMIN000024544 and No. UMIN000024912 PMID:28520754

A Model of Superinfection of Virus-Infected Zebrafish Larvae: Increased Susceptibility to Bacteria Associated With Neutrophil Death

PubMed Central

Boucontet, Laurent; Passoni, Gabriella; Thiry, Valéry; Maggi, Ludovico; Herbomel, Philippe; Levraud, Jean-Pierre; Colucci-Guyon, Emma

2018-01-01

Enhanced susceptibility to bacterial infection in the days following an acute virus infection such as flu is a major clinical problem. Mouse models have provided major advances in understanding viral-bacterial superinfections, yet interactions of the anti-viral and anti-bacterial responses remain elusive. Here, we have exploited the transparency of zebrafish to study how viral infections can pave the way for bacterial co-infections. We have set up a zebrafish model of sequential viral and bacterial infection, using sublethal doses of Sindbis virus and Shigella flexneri bacteria. This virus induces a strong type I interferons (IFN) response, while the bacterium induces a strong IL1β and TNFα-mediated inflammatory response. We found that virus-infected zebrafish larvae showed an increased susceptibility to bacterial infection. This resulted in the death with concomitant higher bacterial burden of the co-infected fish compared to the ones infected with bacteria only. By contrast, infecting with bacteria first and virus second did not lead to increased mortality or microbial burden. By high-resolution live imaging, we showed that neutrophil survival was impaired in Sindbis-then-Shigella co-infected fish. The two types of cytokine responses were strongly induced in co-infected fish. In addition to type I IFN, expression of the anti-inflammatory cytokine IL10 was induced by viral infection before bacterial superinfection. Collectively, these observations suggest the zebrafish larva as a useful animal model to address mechanisms underlying increased bacterial susceptibility upon viral infection. PMID:29881380

A zebrafish (Danio rerio) model of infectious spleen and kidney necrosis virus (ISKNV) infection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu Xiaopeng; Zhang Lichun; Weng Shaoping

2008-06-20

Zebrafish is a model animal for studies of genetics, development, toxicology, oncology, and immunology. In this study, infectious spleen and kidney necrosis virus (ISKNV) was used to establish an infection in zebrafish, and the experimental conditions were established and characterized. Mortality of adult zebrafish infected with ISKNV by intraperitoneal (i.p.) injection exceeded 60%. ISKNV can be passed stably in zebrafish for over ten passages. The ailing zebrafish displayed petechial hemorrhaging and scale protrusion. Histological analysis of moribund fish revealed necrosis of tissue and enlarged cells in kidney and spleen. The real-time RT-PCR analysis of mRNA level confirmed that ISKNV wasmore » replicated in zebrafish. Immunohistochemistry and immunofluorescence analyses further confirmed the presence of ISKNV-infected cells in almost all organs of the infected fish. Electron microscope analyses showed that the ISKNV particle was present in the infected tissues. The establishment of zebrafish infection model of ISKNV can offer a valuable tool for studying the interactions between ISKNV and its host.« less

Treatment model of dengue hemorrhagic fever infection in human body

NASA Astrophysics Data System (ADS)

Handayani, D.; Nuraini, N.; Primasari, N.; Wijaya, K. P.

2014-03-01

The treatment model of DHF presented in this paper involves the dynamic of five time-dependent compartments, i.e. susceptible, infected, free virus particle, immune cell, and haematocrit level. The treatment model is investigated based on normalization of haematocrit level, which is expressed as intravenous fluid infusion control. We analyze the stability of the disease free equilibrium and the endemic equilibrium. The numerical simulations will explain the dynamic of each compartment in human body. These results show particularly that infected compartment and free virus particle compartment are tend to be vanished in two weeks after the onset of dengue virus. However, these simulation results also show that without the treatment, the haematocrit level will decrease even though not up to the normal level. Therefore the effective haematocrit normalization should be done with the treatment control.

Identification of candidate infection genes from the model entomopathogenic nematode Heterorhabditis bacteriophora.

PubMed

Vadnal, Jonathan; Ratnappan, Ramesh; Keaney, Melissa; Kenney, Eric; Eleftherianos, Ioannis; O'Halloran, Damien; Hawdon, John M

2017-01-03

Despite important progress in the field of innate immunity, our understanding of host immune responses to parasitic nematode infections lags behind that of responses to microbes. A limiting factor has been the obligate requirement for a vertebrate host which has hindered investigation of the parasitic nematode infective process. The nematode parasite Heterorhabditis bacteriophora offers great potential as a model to genetically dissect the process of infection. With its mutualistic Photorhabdus luminescens bacteria, H. bacteriophora invades multiple species of insects, which it kills and exploits as a food source for the development of several nematode generations. The ability to culture the life cycle of H. bacteriophora on plates growing the bacterial symbiont makes it a very exciting model of parasitic infection that can be used to unlock the molecular events occurring during infection of a host that are inaccessible using vertebrate hosts. To profile the transcriptional response of an infective nematode during the early stage of infection, we performed next generation RNA sequencing on H. bacteriophora IJs incubated in Manduca sexta hemolymph plasma for 9 h. A subset of up-regulated and down-regulated genes were validated using qRT-PCR. Comparative analysis of the transcriptome with untreated controls found a number of differentially expressed genes (DEGs) which cover a number of different functional categories. A subset of DEGs is conserved across Clade V parasitic nematodes revealing an array of candidate parasitic genes. Our analysis reveals transcriptional changes in the regulation of a large number of genes, most of which have not been shown previously to play a role in the process of infection. A significant proportion of these genes are unique to parasitic nematodes, suggesting the identification of a group of parasitism factors within nematodes. Future studies using these candidates may provide functional insight into the process of nematode parasitism

Human Intestinal Enteroids: a New Model To Study Human Rotavirus Infection, Host Restriction, and Pathophysiology

PubMed Central

Saxena, Kapil; Blutt, Sarah E.; Ettayebi, Khalil; Zeng, Xi-Lei; Broughman, James R.; Crawford, Sue E.; Karandikar, Umesh C.; Sastri, Narayan P.; Conner, Margaret E.; Opekun, Antone R.; Graham, David Y.; Qureshi, Waqar; Sherman, Vadim; Foulke-Abel, Jennifer; In, Julie; Kovbasnjuk, Olga; Zachos, Nicholas C.; Donowitz, Mark

2015-01-01

ABSTRACT Human gastrointestinal tract research is limited by the paucity of in vitro intestinal cell models that recapitulate the cellular diversity and complex functions of human physiology and disease pathology. Human intestinal enteroid (HIE) cultures contain multiple intestinal epithelial cell types that comprise the intestinal epithelium (enterocytes and goblet, enteroendocrine, and Paneth cells) and are physiologically active based on responses to agonists. We evaluated these nontransformed, three-dimensional HIE cultures as models for pathogenic infections in the small intestine by examining whether HIEs from different regions of the small intestine from different patients are susceptible to human rotavirus (HRV) infection. Little is known about HRVs, as they generally replicate poorly in transformed cell lines, and host range restriction prevents their replication in many animal models, whereas many animal rotaviruses (ARVs) exhibit a broader host range and replicate in mice. Using HRVs, including the Rotarix RV1 vaccine strain, and ARVs, we evaluated host susceptibility, virus production, and cellular responses of HIEs. HRVs infect at higher rates and grow to higher titers than do ARVs. HRVs infect differentiated enterocytes and enteroendocrine cells, and viroplasms and lipid droplets are induced. Heterogeneity in replication was seen in HIEs from different patients. HRV infection and RV enterotoxin treatment of HIEs caused physiological lumenal expansion detected by time-lapse microscopy, recapitulating one of the hallmarks of rotavirus-induced diarrhea. These results demonstrate that HIEs are a novel pathophysiological model that will allow the study of HRV biology, including host restriction, cell type restriction, and virus-induced fluid secretion. IMPORTANCE Our research establishes HIEs as nontransformed cell culture models to understand human intestinal physiology and pathophysiology and the epithelial response, including host restriction of

Establishment of pseudovirus infection mouse models for in vivo pharmacodynamics evaluation of filovirus entry inhibitors.

PubMed

Chen, Qing; Tang, Ke; Zhang, Xiaoyu; Chen, Panpan; Guo, Ying

2018-03-01

Filoviruses cause severe and fatal viral hemorrhagic fever in humans. Filovirus research has been extensive since the 2014 Ebola outbreak. Due to their high pathogenicity and mortality, live filoviruses require Biosafety Level-4 (BSL-4) facilities, which have restricted the development of anti-filovirus vaccines and drugs. An HIV-based pseudovirus cell infection assay is widely used for viral entry studies in BSL-2 conditions. Here, we successfully constructed nine in vitro pseudo-filovirus models covering all filovirus genera and three in vivo pseudo-filovirus-infection mouse models using Ebola virus, Marburg virus, and Lloviu virus as representative viruses. The pseudo-filovirus-infected mice showed visualizing bioluminescence in a dose-dependent manner. A bioluminescence peak in mice was reached on day 5 post-infection for Ebola virus and Marburg virus and on day 4 post-infection for Lloviu virus. Two known filovirus entry inhibitors, clomiphene and toremiphene, were used to validate the model. Collectively, our study shows that all genera of filoviruses can be well-pseudotyped and are infectious in vitro . The pseudo-filovirus-infection mouse models can be used for in vivo activity evaluation of anti-filovirus drugs. This sequential in vitro and in vivo evaluation system of filovirus entry inhibitors provides a secure and efficient platform for screening and assessing anti-filovirus agents in BSL-2 facilities.

Modeling malaria infected cells in microcirculation

NASA Astrophysics Data System (ADS)

Raffiee, Amir Hossein; Dabiri, Sadegh; Motavalizadeh Ardekani, Arezoo

2016-11-01

Plasmodim (P.) falciparum is one of the deadliest types of malaria species that invades healthy red blood cells (RBC) in human blood flow. This parasite develops through 48-hour intra-RBC process leading to significant morphological and mechanical (e.g., stiffening) changes in RBC membrane. These changes have remarkable effects on blood circulation such as increase in flow resistance and obstruction in microcirculation. In this work a computational framework is developed to model RBC suspension in blood flow using front-tracking technique. The present study focuses on blood flow behavior under normal and infected circumstances and predicts changes in blood rheology for different levels of parasitemia and hematocrit. This model allows better understanding of blood flow circulation up to a single cell level and provides us with realistic and deep insight into hematologic diseases such as malaria.

A mouse model for studying viscerotropic disease caused by yellow fever virus infection.

PubMed

Meier, Kathryn C; Gardner, Christina L; Khoretonenko, Mikhail V; Klimstra, William B; Ryman, Kate D

2009-10-01

Mosquito-borne yellow fever virus (YFV) causes highly lethal, viscerotropic disease in humans and non-human primates. Despite the availability of efficacious live-attenuated vaccine strains, 17D-204 and 17DD, derived by serial passage of pathogenic YFV strain Asibi, YFV continues to pose a significant threat to human health. Neither the disease caused by wild-type YFV, nor the molecular determinants of vaccine attenuation and immunogenicity, have been well characterized, in large part due to the lack of a small animal model for viscerotropic YFV infection. Here, we describe a small animal model for wild-type YFV that manifests clinical disease representative of that seen in primates without adaptation of the virus to the host, which was required for the current hamster YF model. Investigation of the role of type I interferon (IFN-alpha/beta) in protection of mice from viscerotropic YFV infection revealed that mice deficient in the IFN-alpha/beta receptor (A129) or the STAT1 signaling molecule (STAT129) were highly susceptible to infection and disease, succumbing within 6-7 days. Importantly, these animals developed viscerotropic disease reminiscent of human YF, instead of the encephalitic signs typically observed in mice. Rapid viremic dissemination and extensive replication in visceral organs, spleen and liver, was associated with severe pathologies in these tissues and dramatically elevated MCP-1 and IL-6 levels, suggestive of a cytokine storm. In striking contrast, infection of A129 and STAT129 mice with the 17D-204 vaccine virus was subclinical, similar to immunization in humans. Although, like wild-type YFV, 17D-204 virus amplified within regional lymph nodes and seeded a serum viremia in A129 mice, infection of visceral organs was rarely established and rapidly cleared, possibly by type II IFN-dependent mechanisms. The ability to establish systemic infection and cause viscerotropic disease in A129 mice correlated with infectivity for A129-derived, but not WT

Non-Instrumental Movement Inhibition (NIMI) Differentially Suppresses Head and Thigh Movements during Screenic Engagement: Dependence on Interaction

PubMed Central

Witchel, Harry J.; Santos, Carlos P.; Ackah, James K.; Westling, Carina E. I.; Chockalingam, Nachiappan

2016-01-01

Background: Estimating engagement levels from postural micromovements has been summarized by some researchers as: increased proximity to the screen is a marker for engagement, while increased postural movement is a signal for disengagement or negative affect. However, these findings are inconclusive: the movement hypothesis challenges other findings of dyadic interaction in humans, and experiments on the positional hypothesis diverge from it. Hypotheses: (1) Under controlled conditions, adding a relevant visual stimulus to an auditory stimulus will preferentially result in Non-Instrumental Movement Inhibition (NIMI) of the head. (2) When instrumental movements are eliminated and computer-interaction rate is held constant, for two identically-structured stimuli, cognitive engagement (i.e., interest) will result in measurable NIMI of the body generally. Methods: Twenty-seven healthy participants were seated in front of a computer monitor and speakers. Discrete 3-min stimuli were presented with interactions mediated via a handheld trackball without any keyboard, to minimize instrumental movements of the participant's body. Music videos and audio-only music were used to test hypothesis (1). Time-sensitive, highly interactive stimuli were used to test hypothesis (2). Subjective responses were assessed via visual analog scales. The computer users' movements were quantified using video motion tracking from the lateral aspect. Repeated measures ANOVAs with Tukey post hoc comparisons were performed. Results: For two equivalently-engaging music videos, eliminating the visual content elicited significantly increased non-instrumental movements of the head (while also decreasing subjective engagement); a highly engaging user-selected piece of favorite music led to further increased non-instrumental movement. For two comparable reading tasks, the more engaging reading significantly inhibited (42%) movement of the head and thigh; however, when a highly engaging video game was

Non-Instrumental Movement Inhibition (NIMI) Differentially Suppresses Head and Thigh Movements during Screenic Engagement: Dependence on Interaction.

PubMed

Witchel, Harry J; Santos, Carlos P; Ackah, James K; Westling, Carina E I; Chockalingam, Nachiappan

2016-01-01

Estimating engagement levels from postural micromovements has been summarized by some researchers as: increased proximity to the screen is a marker for engagement, while increased postural movement is a signal for disengagement or negative affect. However, these findings are inconclusive: the movement hypothesis challenges other findings of dyadic interaction in humans, and experiments on the positional hypothesis diverge from it. (1) Under controlled conditions, adding a relevant visual stimulus to an auditory stimulus will preferentially result in Non-Instrumental Movement Inhibition (NIMI) of the head. (2) When instrumental movements are eliminated and computer-interaction rate is held constant, for two identically-structured stimuli, cognitive engagement (i.e., interest) will result in measurable NIMI of the body generally. Twenty-seven healthy participants were seated in front of a computer monitor and speakers. Discrete 3-min stimuli were presented with interactions mediated via a handheld trackball without any keyboard, to minimize instrumental movements of the participant's body. Music videos and audio-only music were used to test hypothesis (1). Time-sensitive, highly interactive stimuli were used to test hypothesis (2). Subjective responses were assessed via visual analog scales. The computer users' movements were quantified using video motion tracking from the lateral aspect. Repeated measures ANOVAs with Tukey post hoc comparisons were performed. For two equivalently-engaging music videos, eliminating the visual content elicited significantly increased non-instrumental movements of the head (while also decreasing subjective engagement); a highly engaging user-selected piece of favorite music led to further increased non-instrumental movement. For two comparable reading tasks, the more engaging reading significantly inhibited (42%) movement of the head and thigh; however, when a highly engaging video game was compared to the boring reading, even though

Agent-based model of fecal microbial transplant effect on bile acid metabolism on suppressing Clostridium difficile infection: an example of agent-based modeling of intestinal bacterial infection.

PubMed

Peer, Xavier; An, Gary

2014-10-01

Agent-based modeling is a computational modeling method that represents system-level behavior as arising from multiple interactions between the multiple components that make up a system. Biological systems are thus readily described using agent-based models (ABMs), as multi-cellular organisms can be viewed as populations of interacting cells, and microbial systems manifest as colonies of individual microbes. Intersections between these two domains underlie an increasing number of pathophysiological processes, and the intestinal tract represents one of the most significant locations for these inter-domain interactions, so much so that it can be considered an internal ecology of varying robustness and function. Intestinal infections represent significant disturbances of this internal ecology, and one of the most clinically relevant intestinal infections is Clostridium difficile infection (CDI). CDI is precipitated by the use of broad-spectrum antibiotics, involves the depletion of commensal microbiota, and alterations in bile acid composition in the intestinal lumen. We present an example ABM of CDI (the C. difficile Infection ABM, or CDIABM) to examine fundamental dynamics of the pathogenesis of CDI and its response to treatment with anti-CDI antibiotics and a newer treatment therapy, fecal microbial transplant. The CDIABM focuses on one specific mechanism of potential CDI suppression: commensal modulation of bile acid composition. Even given its abstraction, the CDIABM reproduces essential dynamics of CDI and its response to therapy, and identifies a paradoxical zone of behavior that provides insight into the role of intestinal nutritional status and the efficacy of anti-CDI therapies. It is hoped that this use case example of the CDIABM can demonstrate the usefulness of both agent-based modeling and the application of abstract functional representation as the biomedical community seeks to address the challenges of increasingly complex diseases with the goal of

Agent-based model of Fecal Microbial Transplant effect on Bile Acid Metabolism on suppressing Clostridium difficile infection: an example of agent-based modeling of intestinal bacterial infection

PubMed Central

Peer, Xavier; An, Gary

2014-01-01

Agent-based modeling is a computational modeling method that represents system-level behavior as arising from multiple interactions between the multiple components that make up a system. Biological systems are thus readily described using agent-based models (ABMs), as multi-cellular organisms can be viewed as populations of interacting cells, and microbial systems manifest as colonies of individual microbes. Intersections between these two domains underlie an increasing number of pathophysiological processes, and the intestinal tract represents one of the most significant locations for these inter-domain interactions, so much so that it can be considered an internal ecology of varying robustness and function. Intestinal infections represent significant disturbances of this internal ecology, and one of the most clinically relevant intestinal infections is Clostridium difficile infection (CDI). CDI is precipitated by the use of broad-spectrum antibiotics, involves the depletion of commensal microbiota, and alterations in bile acid composition in the intestinal lumen. We present an example ABM of CDI (the Clostridium difficile Infection ABM, or CDIABM) to examine fundamental dynamics of the pathogenesis of CDI and its response to treatment with anti-CDI antibiotics and a newer treatment therapy, Fecal Microbial Transplant (FMT). The CDIABM focuses on one specific mechanism of potential CDI suppression: commensal modulation of bile acid composition. Even given its abstraction, the CDIABM reproduces essential dynamics of CDI and its response to therapy, and identifies a paradoxical zone of behavior that provides insight into the role of intestinal nutritional status and the efficacy of anti-CDI therapies. It is hoped that this use case example of the CDIABM can demonstrate the usefulness of both agent-based modeling and the application of abstract functional representation as the biomedical community seeks to address the challenges of increasingly complex diseases with

Metabolic phenotyping in the mouse model of urinary tract infection shows that 3-hydroxybutyrate in plasma is associated with infection

PubMed Central

Xie, Yumin; Yang, Wu; Wang, Yaoyao; Xiang, Wenying; Hylands, Peter J.

2017-01-01

Urinary tract infection is one of the most common bacterial infections worldwide. Current diagnosis of urinary tract infection chiefly relies on its clinical presentation, urine dipstick tests and urine culture. Small molecules found in bio-fluids related with both infection and recovery would facilitate diagnosis and management of UTI. Mass spectrometry-based fingerprinting of plasma and urine at 3 time points, pre-infection (t = -24h), infection (t = 24h) and post 3-day treatment (t = 112h), were acquired in the following four groups: mice which were healthy, infected but not treated, infected and treated with ciprofloxacin, and infected and treated with Relinqing® granules (n = 6 per group). A metabolomics workflow including multivariate analysis and ROC regression was employed to select metabolic features that correlated with UTI and its treatment. Circa 4,000 molecular features were acquired for each sample. The small acid 3-hydroxybutyrate in plasma was found to be differentiated for urinary tract infection, with an area under the curve = 0.97 (95% confidence interval: 0.93–1.00, accuracy = 0.91, sensitivity = 0.92 and specificity = 0.91). The level of 3-hydroxybutyrate in plasma was depleted after infection with a fold change of -22 (q < 0.0001). Correlation between plasma 3-hydroxybutyrate and urine bacterial number in all groups and time points was r = -0.753 (p < 0.0001). The findings show that 3-hydroxybutyrate is depleted in blood and strongly associated with UTI at both infection and post-treatment stage in a UTI mouse model. Further work is envisaged to assess the clinical potential of blood tests to assist with UTI management. PMID:29036204

A growing degree-day model for determination of Fasciola hepatica infection risk in New Zealand with future predictions using climate change models.

PubMed

Haydock, L A J; Pomroy, W E; Stevenson, M A; Lawrence, K E

2016-09-15

Infections of ruminants with Fasciola hepatica are considered to be of regional importance within New Zealand but there is very little recent information on its prevalence or severity other than anecdotal reports. Generally they are considered to be of secondary importance compared to gastrointestinal nematode infections. Utilizing data from Virtual Climate Stations (n=11491) distributed on a 5km grid around New Zealand a growing degree-day model was used to describe the risk of infection with liver fluke from 1972 to 2012 and then to apply the predictions to estimate the risk of fluke infections within New Zealand for the years 2040 and 2090. The growing degree-day model was validated against the most recent survey of infection within New Zealand in 1984. A strong positive linear relationship for 1984 between F. hepatica prevalence in lambs and infection risk (p<0.001; R 2 =0.71) was found indicating the model was effective for New Zealand. A linear regression for risk values from 14 regions in New Zealand for 1972-2012 did not show any discernible change in risk of infection over this time period (p>0.05). Post-hoc comparisons indicate the risk in Westland was found to be substantially higher (p<0.05) than all other regions with Northland ranked second highest. Notable predicted changes in F. hepatica infection risk in 2040 and 2090 were detected although they did vary between different climate change scenarios. The highest average percentage changes in infection risk were found in regions with low initial risk values such as Canterbury and Otago; in these regions 2090 infection risk is expected to rise by an average of 186% and 184%, respectively. Despite the already high levels of infection risk in Westland, values are expected to rise by a further 76% by 2090. The model does show some areas with little change with Taranaki predicted to experience only very minor increases in infection risk with average 2040 and 2090 predicted changes of 0% and 29

Mathematical models of immune effector responses to viral infections: Virus control versus the development of pathology

NASA Astrophysics Data System (ADS)

Wodarz, Dominik

2005-12-01

This article reviews mathematical models which have investigated the importance of lytic and non-lytic immune responses for the control of viral infections. Lytic immune responses fight the virus by killing infected cells, while non-lytic immune responses fight the virus by inhibiting viral replication while leaving the infected cell alive. The models suggest which types or combinations of immune responses are required to resolve infections which vary in their characteristics, such as the rate of viral replication and the rate of virus-induced target cell death. This framework is then applied to persistent infections and viral evolution. It is investigated how viral evolution and antigenic escape can influence the relative balance of lytic and non-lytic responses over time, and how this might correlate with the transition from an asymptomatic infection to pathology. This is discussed in the specific context of hepatitis C virus infection.

Streptozocin-induced diabetic mouse model of urinary tract infection.

PubMed

Rosen, David A; Hung, Chia-Suei; Kline, Kimberly A; Hultgren, Scott J

2008-09-01

Diabetics have a higher incidence of urinary tract infection (UTI), are infected with a broader range of uropathogens, and more commonly develop serious UTI sequelae than nondiabetics. To better study UTI in the diabetic host, we created and characterized a murine model of diabetic UTI using the pancreatic islet beta-cell toxin streptozocin in C3H/HeN, C3H/HeJ, and C57BL/6 mouse backgrounds. Intraperitoneal injections of streptozocin were used to initiate diabetes in healthy mouse backgrounds, as defined by consecutive blood glucose levels of >250 mg/dl. UTIs caused by uropathogenic Escherichia coli (UTI89), Klebsiella pneumoniae (TOP52 1721), and Enterococcus faecalis (0852) were studied, and diabetic mice were found to be considerably more susceptible to infection. All three uropathogens produced significantly higher bladder and kidney titers than buffer-treated controls. Uropathogens did not have as large an advantage in the Toll-like receptor 4-defective C3H/HeJ diabetic mouse, arguing that the dramatic increase in colonization seen in C3H/HeN diabetic mice may partially be due to diabetic-induced defects in innate immunity. Competition experiments demonstrated that E. coli had a significant advantage over K. pneumoniae in the bladders of healthy mice and less of an advantage in diabetic bladders. In the kidneys, K. pneumoniae outcompeted E. coli in healthy mice but in diabetic mice E. coli outcompeted K. pneumoniae and caused severe pyelonephritis. Diabetic kidneys contained renal tubules laden with communities of E. coli UTI89 bacteria within an extracellular-matrix material. Diabetic mice also had glucosuria, which may enhance bacterial replication in the urinary tract. These data support that this murine diabetic UTI model is consistent with known characteristics of human diabetic UTI and can provide a powerful tool for dissecting this infection in the multifactorial setting of diabetes.

A Comprehensive, Model-Based Review of Vaccine and Repeat Infection Trials for Filariasis

PubMed Central

Morris, C. Paul; Evans, Holly; Larsen, Sasha E.

2013-01-01

SUMMARY Filarial worms cause highly morbid diseases such as elephantiasis and river blindness. Since the 1940s, researchers have conducted vaccine trials in 27 different animal models of filariasis. Although no vaccine trial in a permissive model of filariasis has provided sterilizing immunity, great strides have been made toward developing vaccines that could block transmission, decrease pathological sequelae, or decrease susceptibility to infection. In this review, we have organized, to the best of our ability, all published filaria vaccine trials and reviewed them in the context of the animal models used. Additionally, we provide information on the life cycle, disease phenotype, concomitant immunity, and natural immunity during primary and secondary infections for 24 different filaria models. PMID:23824365

Comparison of Stable and Transient Wolbachia Infection Models in Aedes aegypti to Block Dengue and West Nile Viruses.

PubMed

Joubert, Dirk Albert; O'Neill, Scott L

2017-01-01

Pathogen replication and transmission in Wolbachia infected insects are currently studied using three Wolbachia infection systems: naturally infected Wolbachia hosts, hosts transinfected with Wolbachia (stably maintained and inherited infections) and hosts transiently infected with Wolbachia. All three systems have been used to test the effect of Wolbachia on mosquito transmitted pathogens such as dengue virus (DENV), West Nile virus (WNV) and Plasmodium. From these studies it is becoming increasingly clear that the interaction between a particular pathogen and Wolbachia is heavily influenced by the host-Wolbachia interaction and the model of infection. In particular, there is some evidence that under very specific conditions, Wolbachia can enhance pathogen infection in some hosts. In this study, we compared the effect of Wolbachia in two infection models (stable transinfected and transiently infected) on the replication, infection- and transmission rates of two flaviviruses, DENV and WNV (Kunjin strain). Our results indicate that Wolbachia had similar blocking effects in both stable and transient models of infection, however, the magnitude of the blocking effect was significantly lower in mosquitoes transiently infected with Wolbachia. More importantly, no evidence was found for any enhancement of either DENV or WNV (Kunjin strain) infection in Ae. aegypti infected with Wolbachia, supporting a role for Wolbachia as an effective and safe means for restricting transmission of these viruses.

A Lethal Disease Model for Hantavirus Pulmonary Syndrome in Immunosuppressed Syrian Hamsters Infected with Sin Nombre Virus

PubMed Central

Brocato, Rebecca L.; Hammerbeck, Christopher D.; Bell, Todd M.; Wells, Jay B.; Queen, Laurie A.

2014-01-01

Sin Nombre virus (SNV) is a rodent-borne hantavirus that causes hantavirus pulmonary syndrome (HPS) predominantly in North America. SNV infection of immunocompetent hamsters results in an asymptomatic infection; the only lethal disease model for a pathogenic hantavirus is Andes virus (ANDV) infection of Syrian hamsters. Efforts to create a lethal SNV disease model in hamsters by repeatedly passaging virus through the hamster have demonstrated increased dissemination of the virus but no signs of disease. In this study, we demonstrate that immunosuppression of hamsters through the administration of a combination of dexamethasone and cyclophosphamide, followed by infection with SNV, results in a vascular leak syndrome that accurately mimics both HPS disease in humans and ANDV infection of hamsters. Immunosuppressed hamsters infected with SNV have a mean number of days to death of 13 and display clinical signs associated with HPS, including pulmonary edema. Viral antigen was widely detectable throughout the pulmonary endothelium. Histologic analysis of lung sections showed marked inflammation and edema within the alveolar septa of SNV-infected hamsters, results which are similar to what is exhibited by hamsters infected with ANDV. Importantly, SNV-specific neutralizing polyclonal antibody administered 5 days after SNV infection conferred significant protection against disease. This experiment not only demonstrated that the disease was caused by SNV, it also demonstrated the utility of this animal model for testing candidate medical countermeasures. This is the first report of lethal disease caused by SNV in an adult small-animal model. PMID:24198421

A lethal disease model for hantavirus pulmonary syndrome in immunosuppressed Syrian hamsters infected with Sin Nombre virus.

PubMed

Brocato, Rebecca L; Hammerbeck, Christopher D; Bell, Todd M; Wells, Jay B; Queen, Laurie A; Hooper, Jay W

2014-01-01

Sin Nombre virus (SNV) is a rodent-borne hantavirus that causes hantavirus pulmonary syndrome (HPS) predominantly in North America. SNV infection of immunocompetent hamsters results in an asymptomatic infection; the only lethal disease model for a pathogenic hantavirus is Andes virus (ANDV) infection of Syrian hamsters. Efforts to create a lethal SNV disease model in hamsters by repeatedly passaging virus through the hamster have demonstrated increased dissemination of the virus but no signs of disease. In this study, we demonstrate that immunosuppression of hamsters through the administration of a combination of dexamethasone and cyclophosphamide, followed by infection with SNV, results in a vascular leak syndrome that accurately mimics both HPS disease in humans and ANDV infection of hamsters. Immunosuppressed hamsters infected with SNV have a mean number of days to death of 13 and display clinical signs associated with HPS, including pulmonary edema. Viral antigen was widely detectable throughout the pulmonary endothelium. Histologic analysis of lung sections showed marked inflammation and edema within the alveolar septa of SNV-infected hamsters, results which are similar to what is exhibited by hamsters infected with ANDV. Importantly, SNV-specific neutralizing polyclonal antibody administered 5 days after SNV infection conferred significant protection against disease. This experiment not only demonstrated that the disease was caused by SNV, it also demonstrated the utility of this animal model for testing candidate medical countermeasures. This is the first report of lethal disease caused by SNV in an adult small-animal model.

Tracking Human Immunodeficiency Virus-1 Infection in the Humanized DRAG Mouse Model

PubMed Central

Kim, Jiae; Peachman, Kristina K.; Jobe, Ousman; Morrison, Elaine B.; Allam, Atef; Jagodzinski, Linda; Casares, Sofia A.; Rao, Mangala

2017-01-01

Humanized mice are emerging as an alternative model system to well-established non-human primate (NHP) models for studying human immunodeficiency virus (HIV)-1 biology and pathogenesis. Although both NHP and humanized mice have their own strengths and could never truly reflect the complex human immune system and biology, there are several advantages of using the humanized mice in terms of using primary HIV-1 for infection instead of simian immunodeficiency virus or chimera simian/HIV. Several different types of humanized mice have been developed with varying levels of reconstitution of human CD45+ cells. In this study, we utilized humanized Rag1KO.IL2RγcKO.NOD mice expressing HLA class II (DR4) molecule (DRAG mice) infused with HLA-matched hematopoietic stem cells from umbilical cord blood to study early events after HIV-1 infection, since the mucosal tissues of these mice are highly enriched for human lymphocytes and express the receptors and coreceptors needed for HIV-1 entry. We examined the various tissues on days 4, 7, 14, and 21 after an intravaginal administration of a single dose of purified primary HIV-1. Plasma HIV-1 RNA was detected as early as day 7, with 100% of the animals becoming plasma RNA positive by day 21 post-infection. Single cells were isolated from lymph nodes, bone marrow, spleen, gut, female reproductive tissue, and brain and analyzed for gag RNA and strong stop DNA by quantitative (RT)-PCR. Our data demonstrated the presence of HIV-1 viral RNA and DNA in all of the tissues examined and that the virus was replication competent and spread rapidly. Bone marrow, gut, and lymph nodes were viral RNA positive by day 4 post-infection, while other tissues and plasma became positive typically between 7 and 14 days post-infection. Interestingly, the brain was the last tissue to become HIV-1 viral RNA and DNA positive by day 21 post-infection. These data support the notion that humanized DRAG mice could serve as an excellent model for studying the

Pig model mimicking chronic hepatitis E virus infection in immunocompromised patients to assess immune correlates during chronicity

PubMed Central

Cao, Dianjun; Cao, Qian M.; Subramaniam, Sakthivel; Yugo, Danielle M.; Heffron, C. Lynn; Rogers, Adam J.; Kenney, Scott P.; Tian, Debin; Matzinger, Shannon R.; Overend, Christopher; Catanzaro, Nicholas; LeRoith, Tanya; Wang, Heng; Piñeyro, Pablo; Lindstrom, Nicole; Clark-Deener, Sherrie; Yuan, Lijuan; Meng, Xiang-Jin

2017-01-01

Chronic hepatitis E virus (HEV) infection is a significant clinical problem in immunocompromised individuals such as organ transplant recipients, although the mechanism remains unknown because of the lack of an animal model. We successfully developed a pig model of chronic HEV infection and examined immune correlates leading to chronicity. The conditions of immunocompromised patients were mimicked by treating pigs with an immunosuppressive regimen including cyclosporine, azathioprine, and prednisolone. Immunocompromised pigs infected with HEV progressed to chronicity, because 8/10 drug-treated HEV-infected pigs continued fecal virus shedding beyond the acute phase of infection, whereas the majority (7/10) of mock-treated HEV-infected pigs cleared fecal viral shedding at 8 wk postinfection. During chronic infection, serum levels of the liver enzyme γ-glutamyl transferase and fecal virus shedding were significantly higher in immunocompromised HEV-infected pigs. To identify potential immune correlates of chronic infection, we determined serum levels of cytokines and cell-mediated immune responses in pigs. Results showed that HEV infection of immunocompromised pigs reduced the serum levels of Th1 cytokines IL-2 and IL-12, and Th2 cytokines IL-4 and IL-10, particularly during the acute phase of infection. Furthermore IFN-γ–specific CD4+ T-cell responses were reduced in immunocompromised pigs during the acute phase of infection, but TNF-α–specific CD8+ T-cell responses increased during the chronic phase of infection. Thus, active suppression of cell-mediated immune responses under immunocompromised conditions may facilitate the establishment of chronic HEV infection. This pig model will aid in delineating the mechanisms of chronic HEV infection and in developing effective therapeutics against chronic hepatitis E. PMID:28630341

Pig model mimicking chronic hepatitis E virus infection in immunocompromised patients to assess immune correlates during chronicity.

PubMed

Cao, Dianjun; Cao, Qian M; Subramaniam, Sakthivel; Yugo, Danielle M; Heffron, C Lynn; Rogers, Adam J; Kenney, Scott P; Tian, Debin; Matzinger, Shannon R; Overend, Christopher; Catanzaro, Nicholas; LeRoith, Tanya; Wang, Heng; Piñeyro, Pablo; Lindstrom, Nicole; Clark-Deener, Sherrie; Yuan, Lijuan; Meng, Xiang-Jin

2017-07-03

Chronic hepatitis E virus (HEV) infection is a significant clinical problem in immunocompromised individuals such as organ transplant recipients, although the mechanism remains unknown because of the lack of an animal model. We successfully developed a pig model of chronic HEV infection and examined immune correlates leading to chronicity. The conditions of immunocompromised patients were mimicked by treating pigs with an immunosuppressive regimen including cyclosporine, azathioprine, and prednisolone. Immunocompromised pigs infected with HEV progressed to chronicity, because 8/10 drug-treated HEV-infected pigs continued fecal virus shedding beyond the acute phase of infection, whereas the majority (7/10) of mock-treated HEV-infected pigs cleared fecal viral shedding at 8 wk postinfection. During chronic infection, serum levels of the liver enzyme γ-glutamyl transferase and fecal virus shedding were significantly higher in immunocompromised HEV-infected pigs. To identify potential immune correlates of chronic infection, we determined serum levels of cytokines and cell-mediated immune responses in pigs. Results showed that HEV infection of immunocompromised pigs reduced the serum levels of Th1 cytokines IL-2 and IL-12, and Th2 cytokines IL-4 and IL-10, particularly during the acute phase of infection. Furthermore IFN-γ-specific CD4 + T-cell responses were reduced in immunocompromised pigs during the acute phase of infection, but TNF-α-specific CD8 + T-cell responses increased during the chronic phase of infection. Thus, active suppression of cell-mediated immune responses under immunocompromised conditions may facilitate the establishment of chronic HEV infection. This pig model will aid in delineating the mechanisms of chronic HEV infection and in developing effective therapeutics against chronic hepatitis E.

A Novel Model of Asymptomatic Plasmodium Parasitemia That Recapitulates Elements of the Human Immune Response to Chronic Infection

PubMed Central

Baccarella, Alyssa; Craft, Joshua F.; Boyle, Michelle J.; McIntyre, Tara I.; Wood, Matthew D.; Thorn, Kurt S.; Anidi, Chioma; Bayat, Aqieda; Chung, Me Ree; Hamburger, Rebecca; Kim, Chris Y.; Pearman, Emily; Pham, Jennifer; Tang, Jia J.; Boon, Louis; Kamya, Moses R.; Dorsey, Grant; Feeney, Margaret E.; Kim, Charles C.

2016-01-01

In humans, immunity to Plasmodium sp. generally takes the form of protection from symptomatic malaria (i.e., 'clinical immunity') rather than infection ('sterilizing immunity'). In contrast, mice infected with Plasmodium develop sterilizing immunity, hindering progress in understanding the mechanistic basis of clinical immunity. Here we present a novel model in which mice persistently infected with P. chabaudi exhibit limited clinical symptoms despite sustaining patent parasite burdens for many months. Characterization of immune responses in persistently infected mice revealed development of CD4+ T cell exhaustion, increased production of IL-10, and expansion of B cells with an atypical surface phenotype. Additionally, persistently infected mice displayed a dramatic increase in circulating nonclassical monocytes, a phenomenon that we also observed in humans with both chronic Plasmodium exposure and asymptomatic infection. Following pharmacological clearance of infection, previously persistently infected mice could not control a secondary challenge, indicating that persistent infection disrupts the sterilizing immunity that typically develops in mouse models of acute infection. This study establishes an animal model of asymptomatic, persistent Plasmodium infection that recapitulates several central aspects of the immune response in chronically exposed humans. As such, it provides a novel tool for dissection of immune responses that may prevent development of sterilizing immunity and limit pathology during infection. PMID:27583554

Animal Model Reveals Potential Waterborne Transmission of Helicobacter pylori Infection.

PubMed

Boehnke, Kevin F; Eaton, Kathryn A; Valdivieso, Manuel; Baker, Laurence H; Xi, Chuanwu

2015-10-01

Helicobacter pylori infection has been consistently associated with lack of access to clean water and proper sanitation, but no studies have demonstrated that the transmission of H. pylori can occur from drinking contaminated water. In this study, we used a laboratory mouse model to test whether waterborne H. pylori could cause gastric infection. Groups of immunocompetent C57/BL6 Helicobacter-free mice were exposed to static concentrations (1.29 × 10(5), 10(6), 10(7), 10(8), and 10(9) CFU/L) of H. pylori in their drinking water for 4 weeks. One group of Helicobacter-free mice was exposed to uncontaminated water as a negative control. H. pylori morphology changes in water were examined using microscopy Live/Dead staining. Following exposure, H. pylori infection and inflammation status in the stomach were evaluated using quantitative culture, PCR, the rapid urease test, and histology. None of the mice in the negative control or 10(5) groups were infected. One of 20 cages (one of 40 mice) of the 10(6) group, three of 19 cages (four of 38 mice) of the 10(7) CFU/L group, 19 of 20 cages (33 of 40 mice) of the 10(8) group, and 20 of 20 cages (39 of 40 mice) of the 10(9) CFU/L group were infected. Infected mice had significantly higher gastric inflammation than uninfected mice (27.86% higher inflammation, p < .0001). We offer proof that H. pylori in water is infectious in mice, suggesting that humans drinking contaminated water may be at risk of contracting H. pylori infection. Much work needs to be performed to better understand the risk of infection from drinking H. pylori-contaminated water. © 2015 John Wiley & Sons Ltd.

Alternative Host Models for Testing Anti-Protozoal or Antifungal Compounds and Fungal Infection.

PubMed

Torrecilhas, Ana Claudia; Xander, Patricia; Ferreira, Karen Spadari; Batista, Wagner Luiz

2018-01-01

The neglected tropical diseases (NTDs) are caused by several parasites, fungi, bacteria and viruses and affect more than one billion people in the world. The control and prevention against NTDs need implementation of alternative methods for testing new compounds against these diseases. For the implementation of alternative methods, it is necessary to apply the principles of replacement, reduction and refinement (the 3Rs) for the use of laboratory animals. Accordingly, the present review addressed a variety of alternative models to study the infections caused by protozoa and fungi. Overall, vertebrate and invertebrate models of fungal infection have been used to elucidate host-pathogen interactions. However, until now the insect model has not been used in protozoal studies as an alternative method, but there is interest in the scientific community to try new tools to screen alternative drugs to control and prevent protozoal infections. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Modelling the effects of cutting off infected branches and replanting on fire-blight transmission using Filippov systems.