A case of imported tungiasis in Scotland initially mimicking verrucae vulgaris.

PubMed

Wardhaugh, A D; Norris, J F

1994-10-01

A case is described of Tunga penetrans infection in the feet of a tourist returning from South America to Scotland. The condition had initially mimicked verrucae vulgaris, but microscopic examination of the lesions together with the travel history allowed the diagnosis of tungiasis to be made. This is the first case reported in Scotland.

Tension pneumocephalus mimicking septic shock: a case report.

PubMed

Miranda, Caroline; Mahta, Ali; Wheeler, Lee Adam; Tsiouris, A John; Kamel, Hooman

2018-02-01

Tension pneumocephalus can lead to rapid neurologic deterioration. We report for the first time its association with aseptic systemic inflammatory response syndrome mimicking septic shock and the efficacy of prompt neurosurgical intervention and critical care support in treating this condition. A 64-year-old man underwent 2-stage olfactory groove meningioma resection. The patient developed altered mental status and gait instability on postoperative day 6. Imaging showed significant pneumocephalus. The patient subsequently developed worsening mental status, respiratory failure, and profound shock requiring multiple vasopressors. Bedside needle decompression, identification and repair of the cranial fossa defect, and critical care support led to improved mental status and reversal of shock and multiorgan dysfunction. Thorough evaluation revealed no evidence of an underlying infection. In this case, tension pneumocephalus incited an aseptic systemic inflammatory response syndrome mimicking septic shock. Prompt neurosurgical correction of pneumocephalus and critical care support not only improved neurologic status, but also reversed shock. Such a complication indicates the importance of close monitoring of patients with progressive pneumocephalus.

Model of the Phase Transition Mimicking the Pasta Phase in Cold and Dense Quark-Hadron Matter

NASA Astrophysics Data System (ADS)

Ayriyan, Alexander; Grigorian, Hovik

2018-02-01

A simple mixed phase model mimicking so-called "pasta" phases in the quarkhadron phase transition is developed and applied to static neutron stars for the case of DD2 type hadronic and NJL type quark matter models. The influence of the mixed phase on the mass-radius relation of the compact stars is investigated. Model parameters are chosen such that the results are in agreement with the mass-radius constraints.

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

Rational Design of Pathogen-Mimicking Amphiphilic Materials as Nanoadjuvants

NASA Astrophysics Data System (ADS)

Ulery, Bret D.; Petersen, Latrisha K.; Phanse, Yashdeep; Kong, Chang Sun; Broderick, Scott R.; Kumar, Devender; Ramer-Tait, Amanda E.; Carrillo-Conde, Brenda; Rajan, Krishna; Wannemuehler, Michael J.; Bellaire, Bryan H.; Metzger, Dennis W.; Narasimhan, Balaji

2011-12-01

An opportunity exists today for cross-cutting research utilizing advances in materials science, immunology, microbial pathogenesis, and computational analysis to effectively design the next generation of adjuvants and vaccines. This study integrates these advances into a bottom-up approach for the molecular design of nanoadjuvants capable of mimicking the immune response induced by a natural infection but without the toxic side effects. Biodegradable amphiphilic polyanhydrides possess the unique ability to mimic pathogens and pathogen associated molecular patterns with respect to persisting within and activating immune cells, respectively. The molecular properties responsible for the pathogen-mimicking abilities of these materials have been identified. The value of using polyanhydride nanovaccines was demonstrated by the induction of long-lived protection against a lethal challenge of Yersinia pestis following a single administration ten months earlier. This approach has the tantalizing potential to catalyze the development of next generation vaccines against diseases caused by emerging and re-emerging pathogens.

Ecthyma gangrenosum mimicking acute invasive fungal sinusitis in an immunocompromised patient.

PubMed

Hekiert, Adrianna M; Cohen, Michael B; Montone, Kathleen T; Palmer, James N; Govindaraj, Satish

2010-06-01

Ecthyma gangrenosum is a rare necrotizing cutaneous infection usually caused by Pseudomonas aeruginosa. We report a case of ecthyma gangrenosum presenting as a sinonasal eschar and mimicking acute invasive fungal sinusitis in an immunocompromised 39-year-old man with a hematologic malignancy. To the best of our knowledge, this represents the first case of ecthyma gangrenosum affecting the sinonasal mucosa to be reported in the literature.

Human herpesvirus 8-associated lymphoma mimicking cutaneous anaplastic large T-cell lymphoma in a patient with human immunodeficiency virus infection.

PubMed

Li, Meng-Fang; Hsiao, Cheng-Hsiang; Chen, Yi-Lin; Huang, Wen-Ya; Lee, Yi-Hsuan; Huang, Hsien-Neng; Lien, Huang-Chun

2012-02-01

Primary effusion lymphoma, a human herpesvirus 8 (HHV8)-associated lymphoma, is uncommon, and it is usually seen in human immunodeficiency virus (HIV)-infected patients. It presents as a body cavity-based lymphomatous effusion, but several cases of the so-called solid primary effusion lymphoma presenting as solid tumors without associated lymphomatous effusion have been reported. They have similar clinical, histopathological and immunophenotypical features. Most of them have a B-cell genotype. This suggests the solid variant may represent a clinicopathological spectrum of primary effusion lymphoma. We report a case of HHV8-associated lymphoma histopathologically and immunophenotypically mimicking cutaneous anaplastic large cell lymphoma. The patient was a 31-year-old HIV-seropositive man presenting with skin nodules over his right thigh. Biopsy of the nodules showed anaplastic large cells infiltrating the dermis. These malignant cells strongly expressed CD3, CD30 and CD43. Cutaneous anaplastic large T-cell lymphoma was initially diagnosed, but further tests, including immunoreactivity for HHV8 protein and clonal rearrangements of immunoglobulin genes, confirmed the diagnosis of HHV8-associated B-cell lymphoma with aberrant T-cell marker expression. This case provides an example of solid primary effusion lymphoma mimicking cutaneous anaplastic large T-cell lymphoma and highlights the importance of HHV8 immunohistochemistry and molecular tests in the diagnosis of HHV8-associated lymphoma with a cutaneous presentation. Copyright © 2011 John Wiley & Sons A/S.

Multi-modality gellan gum-based tissue-mimicking phantom with targeted mechanical, electrical, and thermal properties.

PubMed

Chen, Roland K; Shih, A J

2013-08-21

This study develops a new class of gellan gum-based tissue-mimicking phantom material and a model to predict and control the elastic modulus, thermal conductivity, and electrical conductivity by adjusting the mass fractions of gellan gum, propylene glycol, and sodium chloride, respectively. One of the advantages of gellan gum is its gelling efficiency allowing highly regulable mechanical properties (elastic modulus, toughness, etc). An experiment was performed on 16 gellan gum-based tissue-mimicking phantoms and a regression model was fit to quantitatively predict three material properties (elastic modulus, thermal conductivity, and electrical conductivity) based on the phantom material's composition. Based on these material properties and the regression model developed, tissue-mimicking phantoms of porcine spinal cord and liver were formulated. These gellan gum tissue-mimicking phantoms have the mechanical, thermal, and electrical properties approximately equivalent to those of the spinal cord and the liver.

Intramuscular Dirofilariasis Mimicking an Orbital Metastasis in a Patient with Breast Cancer

PubMed Central

Henderson, Brett M.; Hunt, Christopher H.; Eckel, Laurence J.; Schwartz, Kara M.; Diehn, Felix E.; Pritt, Bobbi S.; Schembri Wismayer, David J.; Garrity, James A.

2012-01-01

We present the unusual case of a 74 year-old female with a history of breast cancer who presented with acute painless orbital swelling and vertical diplopia. MRI revealed a focal enhancing mass within the superior rectus muscle. As the concern for metastatic disease was high, surgical biopsy was performed and revealed an unusual mimicker of metastatic disease, the parasitic infection dirofilariasis. PMID:23008795

Current Progress of Virus-mimicking Nanocarriers for Drug Delivery

PubMed Central

Somiya, Masaharu; Liu, Qiushi; Kuroda, Shun'ichi

2017-01-01

Nanomedicines often involve the use of nanocarriers as a delivery system for drugs or genes for maximizing the therapeutic effect and/or minimizing the adverse effect. From drug administration to therapeutic activity, nanocarriers must evade the host's immune system, specifically and efficiently target and enter the cell, and release their payload into the cell cytoplasm by endosomal escape. These processes constitute the early infection stage of viruses. Viruses are a powerful natural nanomaterial for the efficient delivery of genetic information by sophisticated mechanisms. Over the past two decades, many virus-inspired nanocarriers have been generated to permit successful drug and gene delivery. In this review, we summarize the early infection machineries of viruses, of which the part has so far been utilized for delivery systems. Furthermore, we describe basics and applications of the bio-nanocapsule, which is a hepatitis B virus-mimicking nanoparticle harboring nearly all activities involved in the early infection machineries (i.e., stealth activity, targeting activity, cell entry activity, endosomal escaping activity). PMID:29188175

A case of cutaneous Rhodotorula infection mimicking cryptococcosis.

PubMed

George, S M C; Quante, M; Cubbon, M D; MacDiarmaid-Gordon, A R; Topham, E J

2016-12-01

Rhodotorula is a ubiquitous environmental and commensal yeast, and an emerging opportunistic pathogen, particularly in immunocompromised individuals. Clinical infections with Rhodotorula have been increasingly recognized over the past 30 years; however, infections in solid-organ transplant recipients are uncommon, and cutaneous manifestations have rarely been reported. We describe a 59-year-old male renal transplant recipient, who developed cutaneous infection with Rhodotorula upon failure of his graft and commencement of haemodialysis. © 2016 British Association of Dermatologists.

Dipylidium caninum mimicking recurrent enterobius vermicularis (pinworm) infection.

PubMed

Samkari, Ayman; Kiska, Deanna L; Riddell, Scott W; Wilson, Kathy; Weiner, Leonard B; Domachowske, Joseph B

2008-05-01

Pinworm infection is a very common diagnosis in young children that is not always confirmed through laboratory evaluation before empiric therapy is prescribed. This article describes a toddler who was treated several times for pinworms because small white worms were seen in her perianal area. Laboratory analysis of parasite material found in her diaper later confirmed a diagnosis of dipylidiasis. Because the signs of dipylidiasis and pinworm infection overlap and the treatments for these parasitic infections are different, the laboratory should clinically confirm suspected persistent or recurrent pinworms.

A Rat Model of Central Venous Catheter to Study Establishment of Long-Term Bacterial Biofilm and Related Acute and Chronic Infections

PubMed Central

Chauhan, Ashwini; Lebeaux, David; Decante, Benoit; Kriegel, Irene; Escande, Marie-Christine; Ghigo, Jean-Marc; Beloin, Christophe

2012-01-01

Formation of resilient biofilms on medical devices colonized by pathogenic microorganisms is a major cause of health-care associated infection. While in vitro biofilm analyses led to promising anti-biofilm approaches, little is known about their translation to in vivo situations and on host contribution to the in vivo dynamics of infections on medical devices. Here we have developed an in vivo model of long-term bacterial biofilm infections in a pediatric totally implantable venous access port (TIVAP) surgically placed in adult rats. Using non-invasive and quantitative bioluminescence, we studied TIVAP contamination by clinically relevant pathogens, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Staphylococcus epidermidis, and we demonstrated that TIVAP bacterial populations display typical biofilm phenotypes. In our study, we showed that immunocompetent rats were able to control the colonization and clear the bloodstream infection except for up to 30% that suffered systemic infection and death whereas none of the immunosuppressed rats survived the infection. Besides, we mimicked some clinically relevant TIVAP associated complications such as port-pocket infection and hematogenous route of colonization. Finally, by assessing an optimized antibiotic lock therapy, we established that our in vivo model enables to assess innovative therapeutic strategies against bacterial biofilm infections. PMID:22615964

Bone tumor mimickers: A pictorial essay

PubMed Central

Mhuircheartaigh, Jennifer Ni; Lin, Yu-Ching; Wu, Jim S

2014-01-01

Focal lesions in bone are very common and many of these lesions are not bone tumors. These bone tumor mimickers can include numerous normal anatomic variants and non-neoplastic processes. Many of these tumor mimickers can be left alone, while others can be due to a significant disease process. It is important for the radiologist and clinician to be aware of these bone tumor mimickers and understand the characteristic features which allow discrimination between them and true neoplasms in order to avoid unnecessary additional workup. Knowing which lesions to leave alone or which ones require workup can prevent misdiagnosis and reduce patient anxiety. PMID:25114385

Micro-scale finite element modeling of ultrasound propagation in aluminum trabecular bone-mimicking phantoms: A comparison between numerical simulation and experimental results.

PubMed

Vafaeian, B; Le, L H; Tran, T N H T; El-Rich, M; El-Bialy, T; Adeeb, S

2016-05-01

The present study investigated the accuracy of micro-scale finite element modeling for simulating broadband ultrasound propagation in water-saturated trabecular bone-mimicking phantoms. To this end, five commercially manufactured aluminum foam samples as trabecular bone-mimicking phantoms were utilized for ultrasonic immersion through-transmission experiments. Based on micro-computed tomography images of the same physical samples, three-dimensional high-resolution computational samples were generated to be implemented in the micro-scale finite element models. The finite element models employed the standard Galerkin finite element method (FEM) in time domain to simulate the ultrasonic experiments. The numerical simulations did not include energy dissipative mechanisms of ultrasonic attenuation; however, they expectedly simulated reflection, refraction, scattering, and wave mode conversion. The accuracy of the finite element simulations were evaluated by comparing the simulated ultrasonic attenuation and velocity with the experimental data. The maximum and the average relative errors between the experimental and simulated attenuation coefficients in the frequency range of 0.6-1.4 MHz were 17% and 6% respectively. Moreover, the simulations closely predicted the time-of-flight based velocities and the phase velocities of ultrasound with maximum relative errors of 20 m/s and 11 m/s respectively. The results of this study strongly suggest that micro-scale finite element modeling can effectively simulate broadband ultrasound propagation in water-saturated trabecular bone-mimicking structures. Copyright © 2016 Elsevier B.V. All rights reserved.

Cervical HSV-2 infection causes cervical remodeling and increases risk for ascending infection and preterm birth.

PubMed

McGee, Devin; Smith, Arianna; Poncil, Sharra; Patterson, Amanda; Bernstein, Alison I; Racicot, Karen

2017-01-01

Preterm birth (PTB), or birth before 37 weeks gestation, is the leading cause of neonatal mortality worldwide. Cervical viral infections have been established as risk factors for PTB in women, although the mechanism leading to increased risk is unknown. Using a mouse model of pregnancy, we determined that intra-vaginal HSV2 infection caused increased rates of preterm birth following an intra-vaginal bacterial infection. HSV2 infection resulted in histological changes in the cervix mimicking cervical ripening, including significant collagen remodeling and increased hyaluronic acid synthesis. Viral infection also caused aberrant expression of estrogen and progesterone receptor in the cervical epithelium. Further analysis using human ectocervical cells demonstrated a role for Src kinase in virus-mediated changes in estrogen receptor and hyaluronic acid expression. In conclusion, HSV2 affects proteins involved in tissue hormone responsiveness, causes significant changes reminiscent of premature cervical ripening, and increases risk of preterm birth. Studies such as this improve our chances of identifying clinical interventions in the future.

Cervical HSV-2 infection causes cervical remodeling and increases risk for ascending infection and preterm birth

PubMed Central

McGee, Devin; Poncil, Sharra; Patterson, Amanda

2017-01-01

Preterm birth (PTB), or birth before 37 weeks gestation, is the leading cause of neonatal mortality worldwide. Cervical viral infections have been established as risk factors for PTB in women, although the mechanism leading to increased risk is unknown. Using a mouse model of pregnancy, we determined that intra-vaginal HSV2 infection caused increased rates of preterm birth following an intra-vaginal bacterial infection. HSV2 infection resulted in histological changes in the cervix mimicking cervical ripening, including significant collagen remodeling and increased hyaluronic acid synthesis. Viral infection also caused aberrant expression of estrogen and progesterone receptor in the cervical epithelium. Further analysis using human ectocervical cells demonstrated a role for Src kinase in virus-mediated changes in estrogen receptor and hyaluronic acid expression. In conclusion, HSV2 affects proteins involved in tissue hormone responsiveness, causes significant changes reminiscent of premature cervical ripening, and increases risk of preterm birth. Studies such as this improve our chances of identifying clinical interventions in the future. PMID:29190738

Melorheostosis mimicking synovial osteochondromatosis.

PubMed

Wadhwa, Vibhor; Chhabra, Avneesh; Samet, Jonathan D

2014-01-01

Melorheostosis is an uncommon, sporadic, sclerosing bone lesion that may affect the adjacent soft tissues. It has been associated with many entities such as osteopoikilosis, soft tissue vascular malformations, bone and soft tissue tumors, nephrotic syndrome, segmental limb contractures, osteosarcoma, desmoid tumor, and mesenteric fibromatosis. Synovial osteochondromatosis is a benign neoplasia of the hyaline cartilage presenting as nodules in the subsynovial tissue of a joint or tendon sheath. The intra-articular extension of melorheostosis mimicking synovial osteochondromatosis has not been reported before. In this article, the authors describe an unusual case mimicking synovial chondromatosis arising as a result of melorheostosis and their characteristic imaging findings.

Development of Vibrational Culture Model Mimicking Vocal Fold Tissues.

PubMed

Kim, Dongjoo; Lim, Jae-Yol; Kwon, Soonjo

2016-10-01

The vocal folds (VFs) are connective tissues with complex matrix structures that provide the required mechanical properties for voice generation. VF injury leads to changes in tissue structure and properties, resulting in reduced voice quality. However, injury-induced biochemical changes and repair in scarred VF tissues have not been well characterized to date. To treat scarred VFs, it is essential to understand how physiological characteristics of VFs tissue change in response to external perturbation. In this study, we designed a simple vibrational culture model to mimic vibratory microenvironments observed in vivo. This model consists of a flexible culture plate, three linear actuators, a stereo splitter, and a function generator. Human vocal fold fibroblast (hVFF) monolayers were established on the flexible membrane, to which normal phonatory vibrations were delivered from linear actuators and a function generator. The hVFF monolayers were exposed to the vibrational stresses at a frequency of 205 Hz for 2, 6, and 10 h with maximum displacement of 47.1 μm, followed by a 6 h rest. We then observed the changes in cell morphology, cell viability, and gene expression related to extracellular matrix components. In our dynamic culture device mimicking normal phonatory frequencies, cell proliferation increased and expression of hyaluronic acid synthase 2 was downregulated in response to vibrational stresses. The results presented herein will be useful for evaluating cellular responses following VF injuries in the presence or absence of vibrational stresses.

The cytopathology of Actinomyces, Nocardia, and their mimickers.

PubMed

McHugh, Kelsey E; Sturgis, Charles D; Procop, Gary W; Rhoads, Daniel D

2017-12-01

Nocardia species and Actinomyces species are 2 of the most commonly diagnosed filamentous bacteria in routine cytopathology practice. These genera share many overlapping cytomorphologic features, including their thin, beaded, branching, Gram-positive, GMS-positive filamentous structures that fragment at their peripheries into bacillary- and coccoid-appearing forms. Features that help distinguish between these 2 microorganisms include the width of their filamentous structures, the angles at which they branch, and their ability or lack thereof to retain a modified acid-fast stain. In addition to cytomorphologic overlap, overlap in clinical presentation is frequent with pulmonary and mucocutaneous presentations seen in both. Differentiating between Nocardia and Actinomyces is essential because patients with these infections require different approaches to medical management. Both antibiotic susceptibilities and the need for early surgical intervention as part of the treatment plan vary greatly among these 2 groups. This review focuses on the clinical presentation, cytomorphology and staining characteristics that can be useful in identifying and distinguishing between Nocardia and Actinomyces infections, as well as their mimickers. © 2017 Wiley Periodicals, Inc.

Oropharyngeal trauma mimicking a first branchial cleft anomaly.

PubMed

Larem, Aisha; Sheikh, Rashid; Al Qahtani, Abdulsalam; Khais, Frat; Ganesan, Shanmugam; Haidar, Hassan

2016-06-01

We present a unique and challenging case of a remnant foreign body that presented to us in a child disguised as a strongly suspected congenital branchial cleft anomaly. This case entailed oropharyngeal trauma, with a delayed presentation as a retroauricular cyst accompanied by otorrhea that mimicked the classic presentation of an infected first branchial cleft anomaly. During surgical excision of the presumed branchial anomaly, a large wooden stick was found in the tract. The diagnostic and therapeutic obstacles in the management of such cases are highlighted. In addition to exploring the existing literature, we retrospectively analyzed a plausible explanation of the findings of this case. Laryngoscope, 126:E224-E226, 2016. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

Facial bacterial infections: folliculitis.

PubMed

Laureano, Ana Cristina; Schwartz, Robert A; Cohen, Philip J

2014-01-01

Facial bacterial infections are most commonly caused by infections of the hair follicles. Wherever pilosebaceous units are found folliculitis can occur, with the most frequent bacterial culprit being Staphylococcus aureus. We review different origins of facial folliculitis, distinguishing bacterial forms from other infectious and non-infectious mimickers. We distinguish folliculitis from pseudofolliculitis and perifolliculitis. Clinical features, etiology, pathology, and management options are also discussed. Copyright © 2014. Published by Elsevier Inc.

Design and Investigation of PolyFermS In Vitro Continuous Fermentation Models Inoculated with Immobilized Fecal Microbiota Mimicking the Elderly Colon

PubMed Central

Fehlbaum, Sophie; Chassard, Christophe; Haug, Martina C.; Fourmestraux, Candice; Derrien, Muriel; Lacroix, Christophe

2015-01-01

In vitro gut modeling is a useful approach to investigate some factors and mechanisms of the gut microbiota independent of the effects of the host. This study tested the use of immobilized fecal microbiota to develop different designs of continuous colonic fermentation models mimicking elderly gut fermentation. Model 1 was a three-stage fermentation mimicking the proximal, transverse and distal colon. Models 2 and 3 were based on the new PolyFermS platform composed of an inoculum reactor seeded with immobilized fecal microbiota and used to continuously inoculate with the same microbiota different second-stage reactors mounted in parallel. The main gut bacterial groups, microbial diversity and metabolite production were monitored in effluents of all reactors using quantitative PCR, 16S rRNA gene 454-pyrosequencing, and HPLC, respectively. In all models, a diverse microbiota resembling the one tested in donor’s fecal sample was established. Metabolic stability in inoculum reactors seeded with immobilized fecal microbiota was shown for operation times of up to 80 days. A high microbial and metabolic reproducibility was demonstrated for downstream control and experimental reactors of a PolyFermS model. The PolyFermS models tested here are particularly suited to investigate the effects of environmental factors, such as diet and drugs, in a controlled setting with the same microbiota source. PMID:26559530

Design and Investigation of PolyFermS In Vitro Continuous Fermentation Models Inoculated with Immobilized Fecal Microbiota Mimicking the Elderly Colon.

PubMed

Fehlbaum, Sophie; Chassard, Christophe; Haug, Martina C; Fourmestraux, Candice; Derrien, Muriel; Lacroix, Christophe

2015-01-01

In vitro gut modeling is a useful approach to investigate some factors and mechanisms of the gut microbiota independent of the effects of the host. This study tested the use of immobilized fecal microbiota to develop different designs of continuous colonic fermentation models mimicking elderly gut fermentation. Model 1 was a three-stage fermentation mimicking the proximal, transverse and distal colon. Models 2 and 3 were based on the new PolyFermS platform composed of an inoculum reactor seeded with immobilized fecal microbiota and used to continuously inoculate with the same microbiota different second-stage reactors mounted in parallel. The main gut bacterial groups, microbial diversity and metabolite production were monitored in effluents of all reactors using quantitative PCR, 16S rRNA gene 454-pyrosequencing, and HPLC, respectively. In all models, a diverse microbiota resembling the one tested in donor's fecal sample was established. Metabolic stability in inoculum reactors seeded with immobilized fecal microbiota was shown for operation times of up to 80 days. A high microbial and metabolic reproducibility was demonstrated for downstream control and experimental reactors of a PolyFermS model. The PolyFermS models tested here are particularly suited to investigate the effects of environmental factors, such as diet and drugs, in a controlled setting with the same microbiota source.

Pathogenic Events in a Nonhuman Primate Model of Oral Poliovirus Infection Leading to Paralytic Poliomyelitis

PubMed Central

Chen, Crystal Y.; Huang, Dan; Wang, Richard; Zhang, Meihong; Qian, Lixia; Zhu, Yanfen; Zhang, Alvin Zhuoran; Yang, Enzhuo; Qaqish, Arwa; Kouiavskaia, Diana; Nathanson, Neal; Macadam, Andrew J.; Andino, Raul; Kew, Olen; Xu, Junfa

2017-01-01

ABSTRACT Despite a great deal of prior research, the early pathogenic events in natural oral poliovirus infection remain poorly defined. To establish a model for study, we infected 39 macaques by feeding them single high doses of the virulent Mahoney strain of wild type 1 poliovirus. Doses ranging from 107 to 109 50% tissue culture infective doses (TCID50) consistently infected all the animals, and many monkeys receiving 108 or 109 TCID50 developed paralysis. There was no apparent difference in the susceptibilities of the three macaque species (rhesus, cynomolgus, and bonnet) used. Virus excretion in stool and nasopharynges was consistently observed, with occasional viremia, and virus was isolated from tonsils, gut mucosa, and draining lymph nodes. Viral replication proteins were detected in both epithelial and lymphoid cell populations expressing CD155 in the tonsil and intestine, as well as in spinal cord neurons. Necrosis was observed in these three cell types, and viral replication in the tonsil/gut was associated with histopathologic destruction and inflammation. The sustained response of neutralizing antibody correlated temporally with resolution of viremia and termination of virus shedding in oropharynges and feces. For the first time, this model demonstrates that early in the infectious process, poliovirus replication occurs in both epithelial cells (explaining virus shedding in the gastrointestinal tract) and lymphoid/monocytic cells in tonsils and Peyer's patches (explaining viremia), extending previous studies of poliovirus pathogenesis in humans. Because the model recapitulates human poliovirus infection and poliomyelitis, it can be used to study polio pathogenesis and to assess the efficacy of candidate antiviral drugs and new vaccines. IMPORTANCE Early pathogenic events of poliovirus infection remain largely undefined, and there is a lack of animal models mimicking natural oral human infection leading to paralytic poliomyelitis. All 39 macaques fed

Pathogenic Events in a Nonhuman Primate Model of Oral Poliovirus Infection Leading to Paralytic Poliomyelitis.

PubMed

Shen, Ling; Chen, Crystal Y; Huang, Dan; Wang, Richard; Zhang, Meihong; Qian, Lixia; Zhu, Yanfen; Zhang, Alvin Zhuoran; Yang, Enzhuo; Qaqish, Arwa; Chumakov, Konstantin; Kouiavskaia, Diana; Vignuzzi, Marco; Nathanson, Neal; Macadam, Andrew J; Andino, Raul; Kew, Olen; Xu, Junfa; Chen, Zheng W

2017-07-15

Despite a great deal of prior research, the early pathogenic events in natural oral poliovirus infection remain poorly defined. To establish a model for study, we infected 39 macaques by feeding them single high doses of the virulent Mahoney strain of wild type 1 poliovirus. Doses ranging from 10 7 to 10 9 50% tissue culture infective doses (TCID 50 ) consistently infected all the animals, and many monkeys receiving 10 8 or 10 9 TCID 50 developed paralysis. There was no apparent difference in the susceptibilities of the three macaque species (rhesus, cynomolgus, and bonnet) used. Virus excretion in stool and nasopharynges was consistently observed, with occasional viremia, and virus was isolated from tonsils, gut mucosa, and draining lymph nodes. Viral replication proteins were detected in both epithelial and lymphoid cell populations expressing CD155 in the tonsil and intestine, as well as in spinal cord neurons. Necrosis was observed in these three cell types, and viral replication in the tonsil/gut was associated with histopathologic destruction and inflammation. The sustained response of neutralizing antibody correlated temporally with resolution of viremia and termination of virus shedding in oropharynges and feces. For the first time, this model demonstrates that early in the infectious process, poliovirus replication occurs in both epithelial cells (explaining virus shedding in the gastrointestinal tract) and lymphoid/monocytic cells in tonsils and Peyer's patches (explaining viremia), extending previous studies of poliovirus pathogenesis in humans. Because the model recapitulates human poliovirus infection and poliomyelitis, it can be used to study polio pathogenesis and to assess the efficacy of candidate antiviral drugs and new vaccines. IMPORTANCE Early pathogenic events of poliovirus infection remain largely undefined, and there is a lack of animal models mimicking natural oral human infection leading to paralytic poliomyelitis. All 39 macaques fed with

[Primary central nervous system lymphoma mimicking ventriculitis].

PubMed

Yamamoto, Shiro; Nagano, Seiji; Shibata, Sumiya; Kunieda, Takeharu; Imai, Yukihiro; Kohara, Nobuo

2013-01-01

A 66-year-old man presented with deteriorated bradykinesia, gait disturbance, disorientation, and urinary incontinence for three weeks. Magnetic resonance imaging (MRI) showed dilatation of the ventricles. Cerebrospinal fluid (CSF) examination demonstrated lymphocytic pleocytosis, elevation of protein levels, and decreased of glucose levels. A gadolinium-enhanced MRI revealed lesions in the ventricular wall and choroid plexus, mimicking ventriculitis. No evidence of bacterial, fungal, mycobacterial, or viral infections were observed in the CSF. Flow cytometry of CSF showed predominance of CD20+, λ+ cells. PCR examination of CSF revealed positive IgH gene rearrangement, suggesting B cell lymphoma. Endoscopic brain biopsy showed diffuse large B cell lymphoma. As the patient had no evidence of lymphoma in the other organs, we made a diagnosed of primary central nervous system lymphoma (PCNSL). A limited intraventricular spread of PCNSL is rare but important as one of differential diagnosis of ventriculitis.

A new prospect in magnetic nanoparticle-based cancer therapy: Taking credit from mathematical tissue-mimicking phantom brain models.

PubMed

Saeedi, Mostafa; Vahidi, Omid; Goodarzi, Vahabodin; Saeb, Mohammad Reza; Izadi, Leila; Mozafari, Masoud

2017-11-01

Distribution patterns/performance of magnetic nanoparticles (MNPs) was visualized by computer simulation and experimental validation on agarose gel tissue-mimicking phantom (AGTMP) models. The geometry of a complex three-dimensional mathematical phantom model of a cancer tumor was examined by tomography imaging. The capability of mathematical model to predict distribution patterns/performance in AGTMP model was captured. The temperature profile vs. hyperthermia duration was obtained by solving bio-heat equations for four different MNPs distribution patterns and correlated with cell death rate. The outcomes indicated that bio-heat model was able to predict temperature profile throughout the tissue model with a reasonable precision, to be applied for complex tissue geometries. The simulation results on the cancer tumor model shed light on the effectiveness of the studied parameters. Copyright © 2017 Elsevier Inc. All rights reserved.

Hypercementosis and odontogenic epithelial hyperplasia associated with a tooth root remnant mimicking a neoplasm. A case report.

PubMed

Zustin, J; Friedrich, R E

2010-01-01

Hypercementosis presents as painless, single or multiple non-neoplastic cementum formation beyond the physiological limits of the tooth. It often occurs in the apical area of the involved tooth following infection, chemical or mechanical trauma. We report on radiographic and histopathological findings in a single case of late intraosseous hypercementosis and odontogenic epithelial hyperplasia associated with a minute apical tooth root remnant years after its extraction, mimicking a tumour.

Tissue mimicking materials for dental ultrasound

PubMed Central

Singh, Rahul S.; Culjat, Martin O.; Grundfest, Warren S.; Brown, Elliott R.; White, Shane N.

2008-01-01

While acoustic tissue mimicking materials have been explored for a variety of soft and hard biological tissues, no dental hard tissue mimicking materials have been characterized. Tooth phantoms are necessary to better understand acoustic phenomenology within the tooth environment and to accelerate the advancement of dental ultrasound imaging systems. In this study, soda lime glass and dental composite were explored as surrogates for human enamel and dentin, respectively, in terms of compressional velocity, attenuation, and acoustic impedance. The results suggest that a tooth phantom consisting of glass and composite can effectively mimic the acoustic behavior of a natural human tooth. PMID:18396919

Autoimmune lymphoproliferative syndrome mimicking chronic active Epstein-Barr virus infection.

PubMed

Nomura, Keiko; Kanegane, Hirokazu; Otsubo, Keisuke; Wakiguchi, Hiroshi; Noda, Yukihiro; Kasahara, Yoshihito; Miyawaki, Toshio

2011-06-01

Chronic active Epstein-Barr virus infection (CAEBV) is defined as a systemic EBV-associated lymphoproliferative disease characterized by fever, lymphadenopathy, and splenomegaly in apparently immunocompetent persons. Recent studies have revealed that EBV infects T or natural killer cells in most patients with CAEBV; the etiology of CAEBV, however, remains unknown. Autoimmune lymphoproliferative disorder (ALPS) is an inherited disorder associated with defects in apoptosis, and clinically characterized by lymphadenopathy, splenomegaly, hypergammaglobulinemia, and autoimmune disease. ALPS is most often associated with mutations in the FAS gene, which is an apoptosis-signaling receptor important for homeostasis of the immune system. Based on the clinical similarity between ALPS and CAEBV with respect to lymphoproliferation, we have examined the possibility of the co-occurrence of ALPS in patients with a diagnosis of CAEBV. In this study, we have identified FAS gene mutations in three Japanese patients with lymphadenopathy, hepatosplenomegaly, and unusual EBV infection, who were diagnosed with CAEBV. These observations, which indicate that the clinical development of ALPS may be associated with EBV infection, alert us to a potential diagnostic pitfall of CAEBV.

M-protein-positive chronic active Epstein-Barr virus infection: features mimicking HIV-1 infection.

PubMed

Imashuku, Shinsaku; Azuma, Naoto; Kanegane, Hirokazu; Kasahara, Yoshihito

2009-09-01

Chronic active Epstein-Barr virus infection (CAEBV) is a unique and fatal lymphoproliferative disease (LPD), which often shows high serum IgG and/or IgE. The significance of such immunoglobulin abnormalities in CAEBV has not been fully evaluated and discussed. In addition, such clinical features mimic HIV-1 infection. We report here a case of CAEBV with M-protein detected which may shed a new light on the pathogenesis of this disease.

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

Microphysiological systems meet hiPSC technology - New tools for disease modeling of liver infections in basic research and drug development.

PubMed

Raasch, Martin; Fritsche, Enrico; Kurtz, Andreas; Bauer, Michael; Mosig, Alexander S

2018-06-14

Complex cell culture models such as microphysiological models (MPS) mimicking human liver functionality in vitro are in the spotlight as alternative to conventional cell culture and animal models. Promising techniques like microfluidic cell culture or micropatterning by 3D bioprinting are gaining increasing importance for the development of MPS to address the needs for more predictivity and cost efficiency. In this context, human induced pluripotent stem cells (hiPSCs) offer new perspectives for the development of advanced liver-on-chip systems by recreating an in vivo like microenvironment that supports the reliable differentiation of hiPSCs to hepatocyte-like cells (HLC). In this review we will summarize current protocols of HLC generation and highlight recently established MPS suitable to resemble physiological hepatocyte function in vitro. In addition, we are discussing potential applications of liver MPS for disease modeling related to systemic or direct liver infections and the use of MPS in testing of new drug candidates. Copyright © 2018. Published by Elsevier B.V.

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

Helminthic infections mimicking malignancy: a review of published case reports.

PubMed

Pilsczek, Florian H

2010-08-04

Infectious diseases, including infections with helminths, can initially present similarly to malignancies. The goal of the article is to review reports of helminthic infections that are initially diagnosed as malignancy. The database PubMed was searched for English language references published as of July 2009. The following published case reports and case series, mainly from Asia and Africa, were identified: Nematodes: 8 publications (1 patient with Angiostrongylus cantonensis, 2 Stronglyloides stercoralis, 1 Toxocara species, 1 Dioctophyma renale, 1 Ascaris species, 1 Gnathostoma spinigerum, 1 Dirofilaria repens); Trematodes: 7 publications (46 patients with Schistosoma species, 2 Fasciola hepatica, 1 Paragonimus westermani); Cestodes: 6 publications (10 patients with Echinococcus species, 1 Sparganum mansoni). To avoid unnecessary investigations and treatment, physicians should be aware when diagnosing patients from Asia or Africa that a large number of helminthic infections can present similar to malignancies.

A blood-mimicking fluid for particle image velocimetry with silicone vascular models

NASA Astrophysics Data System (ADS)

Yousif, Majid Y.; Holdsworth, David W.; Poepping, Tamie L.

2011-03-01

For accurate particle image velocimetry measurements in hemodynamics studies, it is important to use a fluid with a refractive index ( n) matching that of the vascular models (phantoms) and ideally a dynamic viscosity matching human blood. In this work, a blood-mimicking fluid (BMF) composed of water, glycerol, and sodium iodide was formulated for a range of refractive indices to match most common silicone elastomers ( n = 1.40-1.43) and with corresponding dynamic viscosity within the average cited range of healthy human blood (4.4 ± 0.5 cP). Both refractive index and viscosity were attained at room temperature (22.2 ± 0.2°C), which eliminates the need for a temperature-control system. An optimally matched BMF, suitable for use in a vascular phantom ( n = 1.4140 ± 0.0008, Sylgard 184), was demonstrated with composition (by weight) of 47.38% water, 36.94% glycerol (44:56 glycerol-water ratio), and 15.68% sodium iodide salt, resulting in a dynamic viscosity of 4 .31 ± 0 .03 cP.

Biorelevant media resistant co-culture model mimicking permeability of human intestine.

PubMed

Antoine, Delphine; Pellequer, Yann; Tempesta, Camille; Lorscheidt, Stefan; Kettel, Bernadette; Tamaddon, Lana; Jannin, Vincent; Demarne, Frédéric; Lamprecht, Alf; Béduneau, Arnaud

2015-03-15

Cell culture models are currently used to predict absorption pattern of new compounds and formulations in the human gastro-intestinal tract (GIT). One major drawback is the lack of relevant apical incubation fluids allowing mimicking luminal conditions in the GIT. Here, we suggest a culture model compatible with biorelevant media, namely Fasted State Simulated Intestinal Fluid (FaSSIF) and Fed State Simulated Intestinal Fluid (FeSSIF). Co-culture was set up from Caco-2 and mucus-secreting HT29-MTX cells using an original seeding procedure. Viability and cytotoxicity assays were performed following incubation of FeSSIF and FaSSIF with co-culture. Influence of biorelevant fluids on paracellular permeability or transporter proteins were also evaluated. Results were compared with Caco-2 and HT29-MTX monocultures. While Caco-2 viability was strongly affected with FeSSIF, no toxic effect was detected for the co-cultures in terms of viability and lactate dehydrogenase release. The addition of FeSSIF to the basolateral compartment of the co-culture induced cytotoxic effects which suggested the apical mucus barrier being cell protective. In contrast to FeSSIF, FaSSIF induced a slight increase of the paracellular transport and both tested media inhibited partially the P-gp-mediated efflux in the co-culture. Additionally, the absorptive transport of propranolol hydrochloride, a lipophilic β-blocker, was strongly affected by biorelevant fluids. This study demonstrated the compatibility of the Caco-2/HT29-MTX model with some of the current biorelevant media. Combining biorelevant intestinal fluids with features such as mucus secretion, adjustable paracellular and P-gp mediated transports, is a step forward to more realistic in-vitro models of the human intestine. Copyright © 2015. Published by Elsevier B.V.

Heparin-Mimicking Polymers: Synthesis and Biological Applications

PubMed Central

2016-01-01

Heparin is a naturally occurring, highly sulfated polysaccharide that plays a critical role in a range of different biological processes. Therapeutically, it is mostly commonly used as an injectable solution as an anticoagulant for a variety of indications, although it has also been employed in other forms such as coatings on various biomedical devices. Due to the diverse functions of this polysaccharide in the body, including anticoagulation, tissue regeneration, anti-inflammation, and protein stabilization, and drawbacks of its use, analogous heparin-mimicking materials are also widely studied for therapeutic applications. This review focuses on one type of these materials, namely, synthetic heparin-mimicking polymers. Utilization of these polymers provides significant benefits compared to heparin, including enhancing therapeutic efficacy and reducing side effects as a result of fine-tuning heparin-binding motifs and other molecular characteristics. The major types of the various polymers are summarized, as well as their applications. Because development of a broader range of heparin-mimicking materials would further expand the impact of these polymers in the treatment of various diseases, future directions are also discussed. PMID:27739666

Heparin-Mimicking Polymers: Synthesis and Biological Applications.

PubMed

Paluck, Samantha J; Nguyen, Thi H; Maynard, Heather D

2016-11-14

Heparin is a naturally occurring, highly sulfated polysaccharide that plays a critical role in a range of different biological processes. Therapeutically, it is mostly commonly used as an injectable solution as an anticoagulant for a variety of indications, although it has also been employed in other forms such as coatings on various biomedical devices. Due to the diverse functions of this polysaccharide in the body, including anticoagulation, tissue regeneration, anti-inflammation, and protein stabilization, and drawbacks of its use, analogous heparin-mimicking materials are also widely studied for therapeutic applications. This review focuses on one type of these materials, namely, synthetic heparin-mimicking polymers. Utilization of these polymers provides significant benefits compared to heparin, including enhancing therapeutic efficacy and reducing side effects as a result of fine-tuning heparin-binding motifs and other molecular characteristics. The major types of the various polymers are summarized, as well as their applications. Because development of a broader range of heparin-mimicking materials would further expand the impact of these polymers in the treatment of various diseases, future directions are also discussed.

Calvarial sarcoid mimicking metastatic disease.

PubMed

Bodie, B F; Kheir, S M; Omura, E F

1980-10-01

A 61-year-old white woman presented with localized cutaneous Boeck's sarcoid and multiple lytic skull lesions mimicking metastatic carcinoma. Complete workup revealed no neoplastic process; biopsy of the skull lesions showed noncaseating granulomas consistent with sarcoid. Although rare, calvarial sarcoid can occur.

Effects of Chinese medicinal herbs on a rat model of chronic Pseudomonas aeruginosa lung infection.

PubMed

Song, Z; Johansen, H K; Moser, C; Høiby, N

1996-05-01

The aim of the study was to evaluate the effects of two kinds of Chinese medicinal herbs, Isatis tinctoria L (ITL) and Daphne giraldii Nitsche (DGN), on a rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis (CF). Compared to the control group, both drugs were able to reduce the incidence of lung abscess (p < 0.05) and to decrease the severity of the macroscopic pathology in lungs (p < 0.05). In the great majority of the rats, the herbs altered the inflammatory response in the lungs from an acute type inflammation, dominated by polymorphonuclear leukocytes (PMN), to a chronic type inflammation, dominated by mononuclear leukocytes (MN). DGN also improved the clearance of P. aeruginosa from the lungs (p < 0.03) compared with the control group. There were no significant differences between the control group and the two herbal groups with regard to serum IgG and IgA anti-P. aeruginosa sonicate antibodies. However, the IgM concentration in the ITL group was significantly lower than in the control group (p < 0.03). These results suggest that the two medicinal herbs might be helpful to CF patients with chronic P. aeruginosa lung infection, DGN being the most favorable.

Clear cell carcinoma of the ovary mimicking struma ovarii and carcinoid tumor.

PubMed

Alduaij, Ahmad; Quddus, M Ruhul

2011-04-01

Clear cell carcinomas are considered as high-grade tumor often with poor prognosis. We describe 2 cases of clear cell carcinomas of the ovary mimicking benign or less aggressive tumors encountered in the female genital track. The first case is mimicking a benign monodermal teratoma, the so-called struma ovarii, and the second mimicking a carcinoid tumor. Copyright © 2011 Elsevier Inc. All rights reserved.

MIMICKING COUNTERFACTUAL OUTCOMES TO ESTIMATE CAUSAL EFFECTS.

PubMed

Lok, Judith J

2017-04-01

In observational studies, treatment may be adapted to covariates at several times without a fixed protocol, in continuous time. Treatment influences covariates, which influence treatment, which influences covariates, and so on. Then even time-dependent Cox-models cannot be used to estimate the net treatment effect. Structural nested models have been applied in this setting. Structural nested models are based on counterfactuals: the outcome a person would have had had treatment been withheld after a certain time. Previous work on continuous-time structural nested models assumes that counterfactuals depend deterministically on observed data, while conjecturing that this assumption can be relaxed. This article proves that one can mimic counterfactuals by constructing random variables, solutions to a differential equation, that have the same distribution as the counterfactuals, even given past observed data. These "mimicking" variables can be used to estimate the parameters of structural nested models without assuming the treatment effect to be deterministic.

Non-harmful insertion of data mimicking computer network attacks

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

Neil, Joshua Charles; Kent, Alexander; Hash, Jr, Curtis Lee

Non-harmful data mimicking computer network attacks may be inserted in a computer network. Anomalous real network connections may be generated between a plurality of computing systems in the network. Data mimicking an attack may also be generated. The generated data may be transmitted between the plurality of computing systems using the real network connections and measured to determine whether an attack is detected.

Polymerization of a divalent/tetravalent metal-storing atom-mimicking dendrimer.

PubMed

Albrecht, Ken; Hirabayashi, Yuki; Otake, Masaya; Mendori, Shin; Tobari, Yuta; Azuma, Yasuo; Majima, Yutaka; Yamamoto, Kimihisa

2016-12-01

The phenylazomethine dendrimer (DPA) has a layer-by-layer electron density gradient that is an analog of the Bohr atom (atom mimicry). In combination with electron pair mimicry, the polymerization of this atom-mimicking dendrimer was achieved. The valency of the mimicked atom was controlled by changing the chemical structure of the dendrimer. By mimicking a divalent atom, a one-dimensional (1D) polymer was obtained, and by using a planar tetravalent atom mimic, a 2D polymer was obtained. These poly(dendrimer) polymers could store Lewis acids (SnCl 2 ) in their unoccupied orbitals, thus indicating that these poly(dendrimer) polymers consist of a series of nanocontainers.

Cryptococcoma mimicking a brain tumor in an immunocompetent patient: case report of an extremely rare presentation.

PubMed

Paiva, Aline Lariessy Campos; Aguiar, Guilherme Brasileiro de; Lovato, Renan Maximilian; Zanetti, Arthus Vilar Deolindo; Panagopoulos, Alexandros Theodoros; Veiga, José Carlos Esteves

2017-11-06

Central nervous system (CNS) infectious diseases have high prevalence in developing countries and their proper diagnosis and treatment are very important for public health planning. Cryptococcus neoformans is a fungus that may cause several CNS manifestations, especially in immunocompromised patients. Cryptococcal meningitis is the most common type of involvement. Mass-effect lesions are uncommon: they are described as cryptococcomas and their prevalence is even lower among immunocompetent patients. The aim here was to report an extremely rare case of cryptococcoma causing a mass effect and mimicking a brain tumor in an immunocompetent patient. The literature on CNS cryptococcal infections was reviewed with emphasis on cryptococcomas. Clinical, surgical and radiological data on a female patient with this rare presentation of cryptococcoma mimicking a brain tumor are described. A 54-year-old female patient presented to the emergency department with a rapid-onset progressive history of confusion and completely dependency for basic activities. Neuroimaging showed a left occipital lesion and neurosurgical treatment was proposed. From histopathological evaluation, a diagnosis of cryptococcoma was established. She received clinical support with antifungals, but despite optimal clinical treatment, her condition evolved to death. Cryptococcal infections have several forms of presentation and, in immunocompetent patients, their manifestation may be even more different. Cryptococcoma is an extremely rare presentation in which proper surgical and clinical treatment should be instituted as quickly as possible, but even so, there is a high mortality rate.

Breaking Hepatitis B Virus Tolerance and Inducing Protective Immunity Based on Mimicking T Cell-Independent Antigen.

PubMed

Li, Xiaoyan; Ni, Runzhou

2016-11-01

There are over 350 million chronic carriers of hepatitis B virus (HBV) in the world, of whom about a third eventually develop severe HBV-related complications. HBV contributes to liver cirrhosis and hepatocellular carcinoma development. Remarkable progress has been made in selective inhibition of HBV replication by nucleoside analogs. However, how to generate protective antibody of HBsAb in HBV-infected patients after HBV-DNA becomes negative still remains a challenge for scientists. In this study, we show that OmpC-HBsAg 'a' epitope chimeric protein vaccine can break HBV tolerance and induce protective immunity in HBV transgenic mice based on mimicking T cell-independent antigen to bypass T cells from the adaptive immune system. The antibodies induced by the vaccine have the ability to prevent HBV virion infection of human hepatocytes.

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.

The role of ultraviolet colour in the assessment of mimetic accuracy between Batesian mimics and their models: a case study using ant-mimicking spiders

NASA Astrophysics Data System (ADS)

Corcobado, Guadalupe; Herberstein, Marie E.; Pekár, Stano

2016-12-01

The use of ultraviolet (UV) cues for intra- and inter-specific communication is common in many animal species. Still, the role of UV signals under some predator-prey contexts, such as Batesian mimicry, is not clear. Batesian mimicry is a defensive strategy by which a palatable species (the mimic) resembles an unpalatable or noxious species (the model) to avoid predation. This strategy has evolved independently in many different taxa that are predated by species capable of UV perception. Moreover, there is considerable variation in how accurately Batesian mimics resemble their models across species. Our aim was to investigate how UV colour contributed to mimetic accuracy using several ant-mimicking spider species as a case study. We measured the reflectance spectrum (300-700 nm) for several species of mimics and models, and we tested whether they differ in visible and UV colour. We modelled whether two different predators could discriminate between mimics and models using colour information. We found that generally, ant-mimicking spiders differed significantly from their ant models in UV colour and that information from the visible range of light cannot be extrapolated into the UV. Our modelling suggested that wasps should be able to discriminate between mimics and models combining information from visible and the UV light, whereas birds may not discriminate between them. Thus, we show that UV colour can influence mimic accuracy and we discuss its potential role in Batesian mimicry. We conclude that colour, especially in the UV range, should be taken into account when measuring mimetic accuracy.

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

MRI-based morphological modeling, synthesis and characterization of cardiac tissue-mimicking materials.

PubMed

Kossivas, Fotis; Angeli, S; Kafouris, D; Patrickios, C S; Tzagarakis, V; Constantinides, C

2012-06-01

three-dimensional tissue-mimicking models of cardiac anatomy from 2D MR images using rapid prototyping manufacturing processes was developed. For synthesized elastomers, doping strategies with two different concentrations of the MRI contrast agent Dotarem allowed independent and concurrent control of the imaging characteristics (contrast and relaxivity) during the synthetic process for increased contrast agent absorption, with tremendous potential for non-destructive in vivo use and applications to cardiovascular and cerebrovascular diseases.

Pre-university Chemistry Students in a Mimicked Scholarly Peer Review

NASA Astrophysics Data System (ADS)

van Rens, Lisette; Hermarij, Philip; Pilot, Albert; Beishuizen, Jos; Hofman, Herman; Wal, Marjolein

2014-10-01

Peer review is a significant component in scientific research. Introducing peer review into inquiry processes may be regarded as an aim to develop student understanding regarding quality in inquiries. This study examines student understanding in inquiry peer reviews among pre-university chemistry students, aged 16-17, when they enact a design of a mimicked scholarly peer review. This design is based on a model of a human activity system. Twenty-five different schools in Brazil, Germany, Poland and The Netherlands participated. The students (n = 880) conducted in small groups (n = 428) open inquiries on fermentation. All groups prepared an inquiry report for peer review. These reports were published on a website. Groups were randomly paired in an internet symposium, where they posted review comments to their peers. These responses were qualitatively analyzed on small groups' level of understanding regarding seven categories: inquiry question, hypothesis, management of control variables, accurate measurement, presenting results, reliability of results, discussion and conclusion. The mimicked scholarly review prompted a collective practice. Student understanding was significantly well on presenting results, discussion and conclusion, and significantly less on inquiry question and reliability of results. An enacted design, based on a model of a human activity system, created student understanding of quality in inquiries as well as an insight in a peer-reviewing practice. To what extent this model can be applied in a broader context of design research in science education needs further study.

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

Epidemic Model with Isolation in Multilayer Networks

NASA Astrophysics Data System (ADS)

Zuzek, L. G. Alvarez; Stanley, H. E.; Braunstein, L. A.

2015-07-01

The Susceptible-Infected-Recovered (SIR) model has successfully mimicked the propagation of such airborne diseases as influenza A (H1N1). Although the SIR model has recently been studied in a multilayer networks configuration, in almost all the research the isolation of infected individuals is disregarded. Hence we focus our study in an epidemic model in a two-layer network, and we use an isolation parameter w to measure the effect of quarantining infected individuals from both layers during an isolation period tw. We call this process the Susceptible-Infected-Isolated-Recovered (SIIR) model. Using the framework of link percolation we find that isolation increases the critical epidemic threshold of the disease because the time in which infection can spread is reduced. In this scenario we find that this threshold increases with w and tw. When the isolation period is maximum there is a critical threshold for w above which the disease never becomes an epidemic. We simulate the process and find an excellent agreement with the theoretical results.

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.

Autoimmunity to Tropomyosin-Specific Peptides Induced by Mycobacterium leprae in Leprosy Patients: Identification of Mimicking Proteins.

PubMed

Singh, Itu; Yadav, Asha Ram; Mohanty, Keshar Kunja; Katoch, Kiran; Sharma, Prashant; Pathak, Vinay Kumar; Bisht, Deepa; Gupta, Umesh D; Sengupta, Utpal

2018-01-01

It has been shown earlier that there is a rise in the levels of autoantibodies and T cell response to cytoskeletal proteins in leprosy. Our group recently demonstrated a rise in both T and B cell responses to keratin and myelin basic protein in all types of leprosy patients and their associations in type 1 reaction (T1R) group of leprosy. In this study, we investigated the association of levels of autoantibodies and lymphoproliferation against myosin in leprosy patients across the spectrum and tried to find out the mimicking proteins or epitopes between host protein and protein/s of Mycobacterium leprae . One hundred and sixty-nine leprosy patients and 55 healthy controls (HC) were enrolled in the present study. Levels of anti-myosin antibodies and T-cell responses against myosin were measured by ELISA and lymphoproliferation assay, respectively. Using 2-D gel electrophoresis, western blot and MALDI-TOF/TOF antibody-reactive spots were identified. Three-dimensional structure of mimicking proteins was modeled by online server. B cell epitopes of the proteins were predicted by BCPREDS server 1.0 followed by identification of mimicking epitopes. Mice of inbred BALB/c strain were hyperimmunized with M. leprae soluble antigen (MLSA) and splenocytes and lymph node cells of these animals were adoptively transferred to naïve mice. Highest level of anti-myosin antibodies was noted in sera of T1R leprosy patients. We observed significantly higher levels of lymphoproliferative response ( p  < 0.05) with myosin in all types of leprosy patients compared to HC. Further, hyperimmunization of inbred BALB/c strain of female mice and rabbit with MLSA revealed that both hyperimmunized rabbit and mice evoked heightened levels of antibodies against myosin and this autoimmune response could be adoptively transferred from hyperimmunized to naïve mice. Tropomyosin was found to be mimicking with ATP-dependent Clp protease ATP-binding subunit of M. leprae . We found four mimicking

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

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

Undigested Pills in Stool Mimicking Parasitic Infection.

PubMed

Mir, Fazia; Achakzai, Ilyas; Ibdah, Jamal A; Tahan, Veysel

2017-01-01

Background . Orally ingested medications now come in both immediate release and controlled release preparations. Controlled release preparations were developed by pharmaceutical companies to improve compliance and decrease frequency of pill ingestion. Case Report . A 67-year-old obese male patient presented to our clinic with focal abdominal pain that had been present 3 inches below umbilicus for the last three years. This pain was not associated with any trauma or recent heavy lifting. Upon presentation, the patient reported that for the last two months he started to notice pearly oval structures in his stool accompanying his chronic abdominal pain. This had coincided with initiation of his nifedipine pills for his hypertension. He reported seeing these undigested pills daily in his stool. Conclusion . The undigested pills may pose a cause of concern for both patients and physicians alike, as demonstrated in this case report, because they can mimic a parasitic infection. This can result in unnecessary extensive work-up. It is important to review the medication list for extended release formulations and note that the outer shell can be excreted whole in the stool.

Port d’Entrée for Respiratory Infections – Does the Influenza A Virus Pave the Way for Bacteria?

PubMed Central

Siemens, Nikolai; Oehmcke-Hecht, Sonja; Mettenleiter, Thomas C.; Kreikemeyer, Bernd; Valentin-Weigand, Peter; Hammerschmidt, Sven

2017-01-01

Bacterial and viral co-infections of the respiratory tract are life-threatening and present a global burden to the global community. Staphylococcus aureus, Streptococcus pneumoniae, and Streptococcus pyogenes are frequent colonizers of the upper respiratory tract. Imbalances through acquisition of seasonal viruses, e.g., Influenza A virus, can lead to bacterial dissemination to the lower respiratory tract, which in turn can result in severe pneumonia. In this review, we summarize the current knowledge about bacterial and viral co-infections of the respiratory tract and focus on potential experimental models suitable for mimicking this disease. Transmission of IAV and pneumonia is mainly modeled by mouse infection. Few studies utilizing ferrets, rats, guinea pigs, rabbits, and non-human primates are also available. The knowledge gained from these studies led to important discoveries and advances in understanding these infectious diseases. Nevertheless, mouse and other infection models have limitations, especially in translation of the discoveries to humans. Here, we suggest the use of human engineered lung tissue, human ex vivo lung tissue, and porcine models to study respiratory co-infections, which might contribute to a greater translation of the results to humans and improve both, animal and human health. PMID:29312268

Adrenal cortical oncocytoma mimicking pheochromocytoma.

PubMed

Kiriakopoulos, Andreas; Papaioannou, Dimitrios; Linos, Dimitrios

2011-01-01

Adrenal tumors present with clinical features and signs unique to their specific hormonal hypersecretion. However, there have been cases in which the clinical expression has been in conflict with the histologic features of the tumor. In this communication we report an unusual clinical presentation of an adrenal cortical tumor with histologic features of an oncocytoma that clinically mimicked a pheochromocytoma. A 49-year old man was referred to our Unit due to type B aortic dissection and a mass of the left adrenal gland. Computed tomography and magnetic resonance imaging confirmed the presence of aortic dissection extending from the left subclavian artery to both iliac arteries and also revealed a 6 cm tumor on the left adrenal gland. Preoperative endocrine evaluation showed a near tenfold increase of urinary vanillylmandelic acid (VMA) and metanephrine values. Transperitoneal laparoscopic adrenalectomy was successfully performed. The adrenal tumor proved to be an adrenal cortical neoplasm with histologic features of oncocytoma. Although the case of an adrenal cortical adenoma clinically mimicking a pheochromocytoma has been described in the literature, to the best of our knowledge, there has been no previous report of an adrenal cortical neoplasm with predominant features of oncocytoma.

Granulomatosis with polyangiitis mimicking infective endocarditis in an adolescent male.

PubMed

Varnier, Giulia Camilla; Sebire, Neil; Christov, Georgi; Eleftheriou, Despina; Brogan, Paul A

2016-09-01

Granulomatosis with polyangiitis (GPA) is a rare but serious small vessel vasculitis with heterogeneous clinical presentation ranging from mainly localised disease with a chronic course, to a florid, acute small vessel vasculitic form characterised by severe pulmonary haemorrhage and/or rapidly progressive vasculitis or other severe systemic vasculitic manifestations. Cardiac involvement is, however, uncommon in the paediatric population. We report a case of a 16-year-old male who presented with peripheral gangrene and vegetation with unusual location on the supporting apparatus of the tricuspid valve, initially considered to have infective endocarditis but ultimately diagnosed with GPA. We provide an overview of the limited literature relating to cardiac involvement in GPA, and the diagnostic challenge relating to infective endocarditis in this context, especially focusing on the interpretation of the antineutrophil cytoplasmic antibody (ANCA) and the characteristic clinical features to identify in order to promptly recognise GPA, since timely diagnosis and treatment are essential for this potentially life-threatening condition.

Malignant mesenchymal neoplasms of the dermis and subcutis mimicking benign lesions: a case-based review.

PubMed

Mentzel, Thomas; Brenn, Thomas

2017-11-01

In this short review, malignant mesenchymal neoplasms of the dermis and subcutis mimicking benign lesions and their differential diagnoses are discussed. These include plaque-like dermatofibrosarcoma protuberans, superficial low-grade fibromyxoid sarcoma, low-grade superficial malignant peripheral nerve sheath tumour, epithelioid sarcoma, pseudomyogenic haemangioendothelioma, Kaposi sarcoma mimicking cavernous haemangioma and benign lymphangioendothelioma, and rare forms of angiosarcoma mimicking a benign vascular lesion.

Synchrony and motor mimicking in chimpanzee observational learning

PubMed Central

Fuhrmann, Delia; Ravignani, Andrea; Marshall-Pescini, Sarah; Whiten, Andrew

2014-01-01

Cumulative tool-based culture underwrote our species' evolutionary success, and tool-based nut-cracking is one of the strongest candidates for cultural transmission in our closest relatives, chimpanzees. However the social learning processes that may explain both the similarities and differences between the species remain unclear. A previous study of nut-cracking by initially naïve chimpanzees suggested that a learning chimpanzee holding no hammer nevertheless replicated hammering actions it witnessed. This observation has potentially important implications for the nature of the social learning processes and underlying motor coding involved. In the present study, model and observer actions were quantified frame-by-frame and analysed with stringent statistical methods, demonstrating synchrony between the observer's and model's movements, cross-correlation of these movements above chance level and a unidirectional transmission process from model to observer. These results provide the first quantitative evidence for motor mimicking underlain by motor coding in apes, with implications for mirror neuron function. PMID:24923651

Synchrony and motor mimicking in chimpanzee observational learning.

PubMed

Fuhrmann, Delia; Ravignani, Andrea; Marshall-Pescini, Sarah; Whiten, Andrew

2014-06-13

Cumulative tool-based culture underwrote our species' evolutionary success, and tool-based nut-cracking is one of the strongest candidates for cultural transmission in our closest relatives, chimpanzees. However the social learning processes that may explain both the similarities and differences between the species remain unclear. A previous study of nut-cracking by initially naïve chimpanzees suggested that a learning chimpanzee holding no hammer nevertheless replicated hammering actions it witnessed. This observation has potentially important implications for the nature of the social learning processes and underlying motor coding involved. In the present study, model and observer actions were quantified frame-by-frame and analysed with stringent statistical methods, demonstrating synchrony between the observer's and model's movements, cross-correlation of these movements above chance level and a unidirectional transmission process from model to observer. These results provide the first quantitative evidence for motor mimicking underlain by motor coding in apes, with implications for mirror neuron function.

Acute corneal hydrops mimicking full thickness perforation.

PubMed

Ch'ng, S W; Pillai, M B; Aazeem, S; Tu, K L

2012-05-11

A 26-year-old Caucasian female with keratoconus presented with an acutely painful and red left eye. Visual acuity on presentation was 3/60. Slit lamp examination revealed localised Descemet's membrane break with iris partially plugging it. There was a bulging stromal cyst which would intermittently flatten and reform. The appearance when the cyst was flattened mimicked a full thickness corneal perforation. However, no obvious overlying epithelial defect was detected and an intermittent leakage through micro-perforations in the corneal epithelium was the probable cause of the variable appearance. The anterior chamber reformed and iris plug freed following an insertion of a bandage contact lens and taped eyelid. On follow-up, the Descement's membrane had healed with visual acuity improving to 6/18. Our case illustrates the importance of identifying corneal hydrops mimicking a full thickness perforation as conservative management has a greater chance of recovery.

Mesalamine treatment mimicking relapse in a child with ulcerative colitis.

PubMed

Hojsak, Iva; Pavić, Ana M; Kolaček, Sanja

2014-11-01

There are reports on mesalamine-induced bloody diarrhea mimicking ulcerative colitis (UC) relapse, mostly in adults. Herein we present a case of a child with UC who developed relapse of hemorrhagic colitis related to mesalamine. A 10-year-old girl developed severe symptoms mimicking UC relapse 3 weeks after introduction of mesalamine therapy. After mesalamine was withdrawn, her symptoms improved, but deteriorated again during the challenge of mesalamine despite concomitant use of corticosteroids. This is the first case report on such a young child during the concomitant use of corticosteroids.

A Comprehensive Subcellular Proteomic Survey of Salmonella Grown under Phagosome-Mimicking versus Standard Laboratory Conditions

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

Brown, Roslyn N.; Sanford, James A.; Park, Jea H.

Towards developing a systems-level pathobiological understanding of Salmonella enterica, we performed a subcellular proteomic analysis of this pathogen grown under standard laboratory and infection-mimicking conditions in vitro. Analysis of proteins from cytoplasmic, inner membrane, periplasmic, and outer membrane fractions yielded coverage of over 30% of the theoretical proteome. Confident subcellular location could be assigned to over 1000 proteins, with good agreement between experimentally observed location and predicted/known protein properties. Comparison of protein location under the different environmental conditions provided insight into dynamic protein localization and possible moonlighting (multiple function) activities. Notable examples of dynamic localization were the response regulators ofmore » two-component regulatory systems (e.g., ArcB, PhoQ). The DNA-binding protein Dps that is generally regarded as cytoplasmic was significantly enriched in the outer membrane for all growth conditions examined, suggestive of moonlighting activities. These observations imply the existence of unknown transport mechanisms and novel functions for a subset of Salmonella proteins. Overall, this work provides a catalog of experimentally verified subcellular protein location for Salmonella and a framework for further investigations using computational modeling.« less

Anatomical distribution of Mycobacterium bovis genotypes in experimentally infected white-tailed deer

USDA-ARS?s Scientific Manuscript database

Mycobacterium bovis (M. bovis) causes tuberculosis in white-tailed deer (WTD). Natural infection of WTD with M. bovis is most closely mimicked by instilling inoculum into palatine tonsilar crypts. One hundred fifty days after intratonsilar inoculation, M. bovis was cultured from 30 tissues originati...

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.

A modified blade element theory for estimation of forces generated by a beetle-mimicking flapping wing system.

PubMed

Truong, Q T; Nguyen, Q V; Truong, V T; Park, H C; Byun, D Y; Goo, N S

2011-09-01

We present an unsteady blade element theory (BET) model to estimate the aerodynamic forces produced by a freely flying beetle and a beetle-mimicking flapping wing system. Added mass and rotational forces are included to accommodate the unsteady force. In addition to the aerodynamic forces needed to accurately estimate the time history of the forces, the inertial forces of the wings are also calculated. All of the force components are considered based on the full three-dimensional (3D) motion of the wing. The result obtained by the present BET model is validated with the data which were presented in a reference paper. The difference between the averages of the estimated forces (lift and drag) and the measured forces in the reference is about 5.7%. The BET model is also used to estimate the force produced by a freely flying beetle and a beetle-mimicking flapping wing system. The wing kinematics used in the BET calculation of a real beetle and the flapping wing system are captured using high-speed cameras. The results show that the average estimated vertical force of the beetle is reasonably close to the weight of the beetle, and the average estimated thrust of the beetle-mimicking flapping wing system is in good agreement with the measured value. Our results show that the unsteady lift and drag coefficients measured by Dickinson et al are still useful for relatively higher Reynolds number cases, and the proposed BET can be a good way to estimate the force produced by a flapping wing system.

Tick-borne flavivirus infection in Ixodes scapularis larvae: development of a novel method for synchronous viral infection of ticks

PubMed Central

Mitzel, Dana N.; Wolfinbarger, James B.; Daniel Long, R.; Masnick, Max; Best, Sonja M.; Bloom, Marshall E.

2007-01-01

Following a bite from an infected tick, tick-borne flaviviruses cause encephalitis, meningitis and hemorrhagic fever in humans. Although these viruses spend most of their time in the tick, little is known regarding the virus-vector interactions. We developed a simple method for synchronously infecting Ixodes scapularis larvae with Langat virus (LGTV) by immersion in media containing the virus. This technique resulted in approximately 96% of ticks becoming infected. LGTV infection and replication were demonstrated by both viral antigen expression and the accumulation of viral RNA. Furthermore, ticks transmitted LGTV to 100% of the mice and maintained the virus through molting into the next life stage. This technique circumvents limitations present in the current methods by mimicking the natural route of infection and by using attenuated virus strains to infect ticks; thereby, making this technique a powerful tool to study both virus and tick determinants of replication, pathogenesis and transmission. PMID:17490700

Tongue metastasis mimicking an abscess.

PubMed

Mavili, Ertuğrul; Oztürk, Mustafa; Yücel, Tuba; Yüce, Imdat; Cağli, Sedat

2010-03-01

Primary tumors metastasizing to the oral cavity are extremely rare. Lung is one of the most common primary sources of metastases to the tongue. Although the incidence of lung cancer is increasing, tongue metastasis as the initial presentation of the tumor remains uncommon. Due to the rarity of tongue metastasis, little is known about its imaging findings. Herein we report the magnetic resonance imaging and clinical findings of a lingual metastasis, mimicking an abscess, from a primary lung cancer.

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.

Inflammatory Myofibroblastic Tumor Mimicking Apical Periodontitis.

PubMed

Adachi, Makoto; Kiho, Kazuki; Sekine, Genta; Ohta, Takahisa; Matsubara, Makoto; Yoshida, Takakazu; Katsumata, Akitoshi; Tanuma, Jun-ichi; Sumitomo, Shinichiro

2015-12-01

Inflammatory myofibroblastic tumors (IMTs) are rare. IMTs of the head and neck occur in all age groups, from neonates to old age, with the highest incidence occurring in childhood and early adulthood. An IMT has been defined as a histologically distinctive lesion of uncertain behavior. This article describes an unusual case of IMT mimicking apical periodontitis in the mandible of a 42-year-old man. At first presentation, the patient showed spontaneous pain and percussion pain at teeth #28 to 30, which continued after initial endodontic treatment. Panoramic radiography revealed a radiolucent lesion at the site. Cone-beam computed tomographic imaging showed osteolytic lesions, suggesting an aggressive neoplasm requiring incisional biopsy. Histopathological examination indicated an IMT. The lesion was removed en bloc under general anesthesia, and the patient manifested no clinical evidence of recurrence for 24 months. Lesions of nonendodontic origin should be included in the differential diagnosis of apical periodontitis. Every available diagnostic tool should be used to confirm the diagnosis. Cone-beam computed tomographic imaging is very helpful for differential diagnosis in IMTs mimicking apical periodontitis. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

A rabbit model of fatal hypothyroidism mimicking "myxedema coma" established by microscopic total thyroidectomy.

PubMed

Ono, Yosuke; Fujita, Masanori; Ono, Sachiko; Ogata, Sho; Tachibana, Shoichi; Tanaka, Yuji

2016-06-30

Myxedema coma (MC) is a life-threatening endocrine crisis caused by severe hypothyroidism. However, validated diagnostic criteria and treatment guidelines for MC have not been established owing to its rarity. Therefore, a valid animal model is required to investigate the pathologic and therapeutic aspects of MC. The aim of the present study was to establish an animal model of MC induced by total thyroidectomy. We utilized 14 male New Zealand White rabbits anesthetized via intramuscular ketamine and xylazine administration. A total of 7 rabbits were completely thyroidectomized under a surgical microscope (thyroidectomized group) and the remainder underwent sham operations (control group). The animals in both groups were monitored without thyroid hormone replacement for 15 weeks. Pulse rate, blood pressure, body temperature, and electrocardiograms (ECG) were recorded and blood samples were taken from the jugular vein immediately prior to the thyroidectomy and 2 and 4 weeks after surgery. The thyroidectomized rabbits showed a marked reduction of serum thyroxine levels at 4 weeks after the surgical procedure vs. controls (0.50±0.10 vs. 3.32±0.68 μg/dL, p<0.001). Additionally, thyroidectomized rabbits exhibited several signs of hypothyroidism such as hypothermia, systolic hypotension, bradycardia, and low voltage on ECGs, compared with controls. Of the 7 rabbits with severe hypothyroidism, 6 died from 4 to 14 weeks after the thyroidectomy possibly owing to heart failure, because histopathologic examinations revealed a myxedema heart. In summary, we have established a rabbit model of fatal hypothyroidism mimicking MC, which may facilitate pathophysiological and molecular investigations of MC and evaluations of new therapeutic interventions.

[Establishment of sprouting embryoid body model mimicking early embryonic vasculogenesis in human embryo].

PubMed

Jiang, Hua; Feng, You-Ji; Xie, Yi; Han, Jin-Lan; Wang, Zack; Chen, Tong

2008-10-14

To establish a sprouting embryoid body model mimicking early embryonic vasculogenesis in human embryo. Human embryonic stem were (hESCs) were cultured on the mouse embryo fibroblasts and then were induced to differentiate to form three-dimensional EB. The hEBs were cultured in media containing various angiogenesis-related factors: vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), endostatin, angiostatin, and platelet factor (PF)-4 of different concentrations for 3 days to observe the sprouting of the hEBs. 3, 3, 3', 3'-tetramethylindo-carbocyanine perchlorate labeled acetylated low density lipoprotein (Dil-AcLDL) was added onto the hEBs foe 4 h Immunofluorescence assay was used to observe if Dil-AcLDL was absorbed and if CD31 was expressed so as to determine the existence of embryonic endothelial cells in the sprouting structures. The ideal culturing condition was analyzed. The differentiated EBs formed sprouting structures in the collagen I matrix containing VEGF and FGF. The sprouts among individual EBs were able to link to each other and form vascular network-like structures. In the presence of VEGF and FGF, the sprouts branching from the EBs assimilated Dil-AcLDL, expressed CD31 and formed a 3-dimensional cylindrical organization. The concentrations of growth factors ideally stimulating sprouting growth were 100 ng/ml of VEGF and 50 ng/ml of FGF. The networks among the EBs were abolished by the angiostatin, endostatin, and PF4. The sprouting from hEBs accumulates embryonic endothelial cells and the sprouting network-like structures are indeed endothelial in nature. Inducing of sprouting EBs is an ideal model that mimics early embryonic vasculogenesis in humans.

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.

A role for Toll-like receptor 4 in the host response to the lung infection of Yersinia pseudotuberculosis in mice.

PubMed

Choi, Jin-A; Jeong, Yu-Jin; Kim, Jae-Eun; Kang, Min-Jung; Kim, Jee-Cheon; Oh, Sang-Muk; Lee, Kyung-Bok; Kim, Dong-Hyun; Kim, Dong-Jae; Park, Jong-Hwan

2016-02-01

Although a Yersinia pseudotuberculosis (Yptb) lung infection model has been developed to study Y. pestis pathogenesis, it is still necessary to establish a new animal model to mimic the pathophysiological features induced by Y. pestis infection. Here, we provide a new lung infection model using the Yptb strain, IP2777, which displayed rapid spread of bacteria to the liver, spleen, and blood. In addition, we examined whether TLR4 is involved in Yptb-induced pathogenesis in the lung infection model of mice we generated. Following lung infection of WT and TLR4-deficient mice with the Yptb strain IP2777, the survival rate, bacterial colonization, histopathology, and level of cytokines and chemokines in the lung, spleen, liver, and blood were analyzed. TLR4-deficient mice had a lower survival rate than WT mice in response to Yptb lung infection. Although the bacterial colonization and pathology of the lung were comparable between WT and TLR4-deficient mice, those of the spleen and liver were more severe in TLR4-deficient mice. In addition, the levels of TNF-α and CXCL2 in the liver and IL-6 and CXCL2 in the blood were higher in TLR4-deficient mice than in WT mice. Our results demonstrate that TLR4 is necessary for optimal host protection against Yptb lung infection and TLR4-deficient mice may serve as a better genetic model of Yptb infection for mimicking Y. pestis infection. Copyright © 2016 Elsevier Ltd. All rights reserved.

Deep Granuloma Annulare Mimicking Inflamed Cysts in a Teenager.

PubMed

Guo, Emily L; Degesys, Catherine A; Jahan-Tigh, Richard; Chan, Audrey

2017-07-01

We describe deep granuloma annulare (DGA) of the forehead mimicking inflamed cysts. Reactive inflammation and sterile purulent drainage may be an underrecognized feature of DGA. © 2017 Wiley Periodicals, Inc.

Rabbit aortic aneurysm model with enlarging diameter capable of better mimicking human aortic aneurysm disease.

PubMed

Bi, Yonghua; Chen, Hongmei; Li, Yahua; Yu, Zepeng; Han, Xinwei; Ren, Jianzhuang

2018-01-01

The self-healing phenomenon can be found in the elastase-induced abdominal aortic aneurysm (AAA) model, and an enlarging AAA model was successfully induced by coarctation. Unfortunately, aortic coarctation in these enlarging models is generally not found in human AAA disease. This study aimed to create an experiment model of enlarging AAA in rabbits to better mimic human aortic aneurysm disease. Eighty-four male New Zealand white rabbits were randomly divided into three equal groups: two aneurysm groups (A and B) and a SHAM group. Aneurysm group rabbits underwent extrinsic aortic stenosis below the right renal artery and received a 10-minute incubation of 60 μl elastase (1 unit/μl). Absorbable suture was used in Group A and nonabsorbable cotton thread was used in Group B. A sham operation was performed in the SHAM group. Aortic diameter was measured after 1, 3, 7, and 15 weeks; thereafter animals were sacrificed for histopathological, immunohistochemical and quantitative studies. Two rabbits died at 29 and 48 days, respectively, after operation in Group B. All aneurysms formed and enlarged progressively by 3 weeks in the Aneurysm groups. However, diameter enlargement in Group A was significantly lower than that in Group B at 7 weeks. Aneurysm groups developed intimal hyperplasia; intima-media thickness (IMT) increased significantly by week 7, and aortic media thickness and intima-media ratio (IMR) increased significantly by week 15. Marked destruction of elastin fibers and smooth muscle cells (SMCs) occurred 1 week later and increased progressively thereafter. Intimal hyperplasia and SMCs content in Group A increased significantly by week 15 compared with Group B. Aneurysm groups exhibited strong expression of matrix metalloproteinases 2 and 9 and RAM11 by week 1, and decreased progressively thereafter. In conclusion, this novel rabbit AAA model enlarges progressively without coarctation and is capable of better mimicking human aortic aneurysm disease.

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.

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.

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.

Antibacterial metabolites secreted under glucose-limited environment of the mimicked proximal colon model by lactobacilli abundant in infant feces.

PubMed

Kanjan, Pochanart; Hongpattarakere, Tipparat

2016-09-01

The most abundance of anti-Salmonella lactic acid bacteria (LAB) was found in feces of naturally born, exclusively breastfed Thai infants. Six strains of Lactobacillus plantarum and one strain of Lactobacillus paracasei were selected and identified. In the co-cultivation assay, L. plantarum subsp. plantarum I62 showed the strongest and broadest antibacterial activity against Escherichia coli, Shigella sonnei, Salmonella Paratyphi A, and Salmonella Typhimurium SA 2093 under the mimicked proximal colon condition, in which glucose and other nutrients were limited. According to GC-MS analysis, the major antibacterial contribution of organic acids secreted by L. plantarum I62 grown in the presence of glucose was dramatically reduced from 95.8 to 41.9 % under glucose-limited niche. The production of low-pK a acids, such as lactic, 1,2-benzenedicarboxylic, and 3-phenyllactic acids, was remarkably dropped. Surprisingly, higher-pK a acids such as 5-chlorobenzimidazole-2-carboxylic, pyroglutamic, palmitic, and oleic acids were enhanced. Moreover, cyclic dipeptides, ketones, alkanes, alcohols, and miscellaneous compounds, which were pH-independent antibacterial metabolites, became dominant. The electron microscopy strongly supported the synergistic attacks of the multiple antibacterial components targeting outer and cytoplasmic membranes leading to severe leakage and cell disruption of Salmonella Typhimurium. This strain poses to be a potential probiotic candidate for effectively controlling and treating human foodborne bacterial infection.

Rare extraskeletal Ewing's sarcoma mimicking as adenocarcinoma of the sigmoid.

PubMed

Mertens, Michelle; Haenen, Filip W N; Siozopoulou, Vasiliki; Van Cleemput, Marc

2017-06-01

Extraskeletal Ewing's sarcoma (EES) is a rare finding in comparison with Ewing's sarcoma of bone and usually manifests in young patients. However, even in older patients, one must consider the diagnosis. In this case, we describe a 52-year-old woman diagnosed with EES, mimicking as adenocarcinoma of the sigmoid. The tumor was not visualized by a multi-slice spiral computed tomography of the abdomen and pelvis with intravenous contrast, and eventually the diagnosis was made by positive immunohistochemical staining for CD99 and by molecular testing for EWSR1 translocation. This combination of the patient's age and the localization of the tumor mimicking an adenocarcinoma of the sigmoid has never been described before.

Cerebello-cortical network fingerprints differ between essential, Parkinson's and mimicked tremors.

PubMed

Muthuraman, Muthuraman; Raethjen, Jan; Koirala, Nabin; Anwar, Abdul Rauf; Mideksa, Kidist G; Elble, Rodger; Groppa, Sergiu; Deuschl, Günter

2018-06-01

Cerebello-thalamo-cortical loops play a major role in the emergence of pathological tremors and voluntary rhythmic movements. It is unclear whether these loops differ anatomically or functionally in different types of tremor. We compared age- and sex-matched groups of patients with Parkinson's disease or essential tremor and healthy controls (n = 34 per group). High-density 256-channel EEG and multi-channel EMG from extensor and flexor muscles of both wrists were recorded simultaneously while extending the hands against gravity with the forearms supported. Tremor was thereby recorded from patients, and voluntarily mimicked tremor was recorded from healthy controls. Tomographic maps of EEG-EMG coherence were constructed using a beamformer algorithm coherent source analysis. The direction and strength of information flow between different coherent sources were estimated using time-resolved partial-directed coherence analyses. Tremor severity and motor performance measures were correlated with connection strengths between coherent sources. The topography of oscillatory coherent sources in the cerebellum differed significantly among the three groups, but the cortical sources in the primary sensorimotor region and premotor cortex were not significantly different. The cerebellar and cortical source combinations matched well with known cerebello-thalamo-cortical connections derived from functional MRI resting state analyses according to the Buckner-atlas. The cerebellar sources for Parkinson's tremor and essential tremor mapped primarily to primary sensorimotor cortex, but the cerebellar source for mimicked tremor mapped primarily to premotor cortex. Time-resolved partial-directed coherence analyses revealed activity flow mainly from cerebellum to sensorimotor cortex in Parkinson's tremor and essential tremor and mainly from cerebral cortex to cerebellum in mimicked tremor. EMG oscillation flowed mainly to the cerebellum in mimicked tremor, but oscillation flowed mainly

PAM: Particle automata model in simulation of Fusarium graminearum pathogen expansion.

PubMed

Wcisło, Rafał; Miller, S Shea; Dzwinel, Witold

2016-01-21

The multi-scale nature and inherent complexity of biological systems are a great challenge for computer modeling and classical modeling paradigms. We present a novel particle automata modeling metaphor in the context of developing a 3D model of Fusarium graminearum infection in wheat. The system consisting of the host plant and Fusarium pathogen cells can be represented by an ensemble of discrete particles defined by a set of attributes. The cells-particles can interact with each other mimicking mechanical resistance of the cell walls and cell coalescence. The particles can move, while some of their attributes can be changed according to prescribed rules. The rules can represent cellular scales of a complex system, while the integrated particle automata model (PAM) simulates its overall multi-scale behavior. We show that due to the ability of mimicking mechanical interactions of Fusarium tip cells with the host tissue, the model is able to simulate realistic penetration properties of the colonization process reproducing both vertical and lateral Fusarium invasion scenarios. The comparison of simulation results with micrographs from laboratory experiments shows encouraging qualitative agreement between the two. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

Electrocardiogram artifact caused by rigors mimicking narrow complex tachycardia: a case report.

PubMed

Matthias, Anne Thushara; Indrakumar, Jegarajah

2014-02-04

The electrocardiogram (ECG) is useful in the diagnosis of cardiac and non-cardiac conditions. Rigors due to shivering can cause electrocardiogram artifacts mimicking various cardiac rhythm abnormalities. We describe an 80-year-old Sri Lankan man with an abnormal electrocardiogram mimicking narrow complex tachycardia during the immediate post-operative period. Electrocardiogram changes caused by muscle tremor during rigors could mimic a narrow complex tachycardia. Identification of muscle tremor as a cause of electrocardiogram artifact can avoid unnecessary pharmacological and non-pharmacological intervention to prevent arrhythmias.

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.

Human in vitro 3D co-culture model to engineer vascularized bone-mimicking tissues combining computational tools and statistical experimental approach.

PubMed

Bersini, Simone; Gilardi, Mara; Arrigoni, Chiara; Talò, Giuseppe; Zamai, Moreno; Zagra, Luigi; Caiolfa, Valeria; Moretti, Matteo

2016-01-01

The generation of functional, vascularized tissues is a key challenge for both tissue engineering applications and the development of advanced in vitro models analyzing interactions among circulating cells, endothelium and organ-specific microenvironments. Since vascularization is a complex process guided by multiple synergic factors, it is critical to analyze the specific role that different experimental parameters play in the generation of physiological tissues. Our goals were to design a novel meso-scale model bridging the gap between microfluidic and macro-scale studies, and high-throughput screen the effects of multiple variables on the vascularization of bone-mimicking tissues. We investigated the influence of endothelial cell (EC) density (3-5 Mcells/ml), cell ratio among ECs, mesenchymal stem cells (MSCs) and osteo-differentiated MSCs (1:1:0, 10:1:0, 10:1:1), culture medium (endothelial, endothelial + angiopoietin-1, 1:1 endothelial/osteo), hydrogel type (100%fibrin, 60%fibrin+40%collagen), tissue geometry (2 × 2 × 2, 2 × 2 × 5 mm(3)). We optimized the geometry and oxygen gradient inside hydrogels through computational simulations and we analyzed microvascular network features including total network length/area and vascular branch number/length. Particularly, we employed the "Design of Experiment" statistical approach to identify key differences among experimental conditions. We combined the generation of 3D functional tissue units with the fine control over the local microenvironment (e.g. oxygen gradients), and developed an effective strategy to enable the high-throughput screening of multiple experimental parameters. Our approach allowed to identify synergic correlations among critical parameters driving microvascular network development within a bone-mimicking environment and could be translated to any vascularized tissue. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

Tuberculous pleurisy mimicking Mycoplasma pneumoniae infection in a previously healthy young adult: A case report.

PubMed

Yaguchi, Daizo; Ichikawa, Motoshi; Shizu, Masato; Inoue, Noriko; Kobayashi, Daisuke; Imai, Naoyuki; Ito, Masao

2018-05-01

Sometimes, pleural effusion accompanying an acute Mycoplasma pneumoniae infection or tuberculous pleurisy has similar analysis results. We report a case of tuberculous pleurisy which was initially diagnosed as acute M pneumoniae infection, which is of special interest because anti-Mycoplasma antibody results were positive, which served as a red herring. A 20-year-old woman visited the outpatient emergency romm of our hospital for chief complaints of high fever, dry cough, and pleuralgia persiting for 2 days. Since anti-mycoplasma antibody test results were positive, we treated acute M pneumoniae infection and drained her pleural effusion. The condition tended to improve, but on day 16 postadmission, the acid-fast bacterial culture of the pleural effusion was positive for Mycobacterium tuberculosis. Tuberculous pleurisy. After the diagnosis, the patient received antituberculous drugs. She completed treatment with no noticeable adverse events, and the right pleural effusion disappered and diffuse right pleural thickening improved. Exudative pleural effusion with lymphocyte dominance and a high adenosine deaminase level in M pneumoniae infection have been reported. Even though the condition suggests acute M pneumoniae infection, clinicians should be aware that tuberculous pleurisy and M pneumoniae infection can share similar clinical features, and should understand the usefulness and limitations of the anit-Mycoplasma antibody test.

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

Methyl-orvinol-Dual activity opioid receptor ligand inhibits gastrointestinal transit and alleviates abdominal pain in the mouse models mimicking diarrhea-predominant irritable bowel syndrome.

PubMed

Zielińska, Marta; Jarmuż, Agata; Wasilewski, Andrzej; Cami-Kobeci, Gerta; Husbands, Stephen; Fichna, Jakub

2017-04-01

Diarrhea-predominant irritable bowel syndrome (IBS-D) is a functional disorder of the gastrointestinal (GI) tract. The major IBS-D symptoms include diarrhea, abdominal pain and discomfort. High density of opioid receptors (ORs) in the GI tract and their participation in the maintenance of GI homeostasis make ORs ligands an attractive option for developing new anti-IBS-D treatments. The aim of this study was to characterize the effect of methyl-orvinol on the GI motility and secretion and in mouse models mimicking symptoms of IBS-D. In vitro, the effects of methyl-orvinol on electrical field stimulated smooth muscle contractility and epithelial ion transport were characterized in the mouse colon. In vivo, the following tests were used to determine methyl-orvinol effect on mouse GI motility: colonic bead expulsion, whole GI transit and fecal pellet output. An antinociceptive action of methyl-orvinol was assessed in the mouse model of visceral pain induced by mustard oil. Methyl-orvinol (10 -10 to 10 -6 M) inhibited colonic smooth muscle contractions in a concentration-dependent manner. This effect was reversed by naloxone (non-selective opioid antagonist) and β-funaltrexamine (selective MOP antagonist). Experiments with a selective KOP receptor agonist, U50488 revealed that methyl-orvinol is a KOP receptor antagonist in the GI tract. Methyl-orvinol enhanced epithelial ion transport. In vivo, methyl-orvinol inhibited colonic bead expulsion and prolonged GI transit. Methyl-orvinol improved hypermotility and reduced abdominal pain in the mouse models mimicking IBS-D symptoms. Methyl-orvinol could become a promising drug candidate in chronic therapy of functional GI diseases such as IBS-D. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Evidence of proteolipid domain formation in an inner mitochondrial membrane mimicking model.

PubMed

Cheniour, Mouhedine; Brewer, Jonathan; Bagatolli, Luis; Marcillat, Olivier; Granjon, Thierry

2017-05-01

Mitochondrial creatine kinase (mtCK) is highly abundant in mitochondria; its quantity is equimolecular to the Adenylic Nucleotide Translocator and represents 1% of the mitochondrial proteins. It is a multitask protein localized in the mitochondria intermembrane space where it binds to the specific cardiolipin (CL) phospholipid. If mtCK was initially thought to be exclusively implicated in energy transfer between mitochondria and cytosol through a mechanism referred to as the phosphocreatine shuttle, several recent studies suggested an additional role in maintaining mitochondria membrane structure. To further characterized mtCK binding process we used multiphoton excitation fluorescence microscopy coupled with Giant Unilamellar Vesicles (GUV) and laurdan as fluorescence probe. We gathered structural and dynamical information on the molecular events occurring during the binding of mtCK to the mitochondria inner membrane. We present the first visualization of mtCK-induced CL segregation on a bilayer model forming micrometer-size proteolipid domains at the surface of the GUV. Those microdomains, which only occurred when CL is included in the lipid mixture, were accompanied by the formation of protein multimolecular assembly, vesicle clamping, and changes in both vesicle curvature and membrane fluidity CONCLUSION: Those results highlighted the importance of the highly abundant mtCK in the lateral organization of the mitochondrial inner membrane. Microdomains were induced in mitochondria-mimicking membranes composed of natural phospholipids without cholesterol and/or sphingolipids differing from the proposed cytoplasmic membrane rafts. Those findings as well as membrane curvature modification were discussed in relation with protein-membrane interaction and protein cluster involvement in membrane morphology. Copyright © 2017 Elsevier B.V. All rights reserved.

Bio-mimicking nano and micro-structured surface fabrication for antibacterial properties in medical implants.

PubMed

Jaggessar, Alka; Shahali, Hesam; Mathew, Asha; Yarlagadda, Prasad K D V

2017-10-02

Orthopaedic and dental implants have become a staple of the medical industry and with an ageing population and growing culture for active lifestyles, this trend is forecast to continue. In accordance with the increased demand for implants, failure rates, particularly those caused by bacterial infection, need to be reduced. The past two decades have led to developments in antibiotics and antibacterial coatings to reduce revision surgery and death rates caused by infection. The limited effectiveness of these approaches has spurred research into nano-textured surfaces, designed to mimic the bactericidal properties of some animal, plant and insect species, and their topographical features. This review discusses the surface structures of cicada, dragonfly and butterfly wings, shark skin, gecko feet, taro and lotus leaves, emphasising the relationship between nano-structures and high surface contact angles on self-cleaning and bactericidal properties. Comparison of these surfaces shows large variations in structure dimension and configuration, indicating that there is no one particular surface structure that exhibits bactericidal behaviour against all types of microorganisms. Recent bio-mimicking fabrication methods are explored, finding hydrothermal synthesis to be the most commonly used technique, due to its environmentally friendly nature and relative simplicity compared to other methods. In addition, current proposed bactericidal mechanisms between bacteria cells and nano-textured surfaces are presented and discussed. These models could be improved by including additional parameters such as biological cell membrane properties, adhesion forces, bacteria dynamics and nano-structure mechanical properties. This paper lastly reviews the mechanical stability and cytotoxicity of micro and nano-structures and materials. While the future of nano-biomaterials is promising, long-term effects of micro and nano-structures in the body must be established before nano-textures can

Imaging findings of mimickers of hepatocellular carcinoma

PubMed Central

Lee, Eunchae; Jang, Hyun-Jung

2015-01-01

Radiological imaging plays a crucial role in the diagnosis of hepatocellular carcinoma (HCC) as the noninvasive diagnosis of HCC in high-risk patients by typical imaging findings alone is widely adopted in major practice guidelines for HCC. While imaging techniques have markedly improved in detecting small liver lesions, they often detect incidental benign liver lesions and non-hepatocellular malignancy that can be misdiagnosed as HCC. The most common mimicker of HCC in cirrhotic liver is nontumorous arterioportal shunts that are seen as focal hypervascular liver lesions on dynamic contrast-enhanced cross-sectional imaging. Rapidly enhancing hemangiomas can be easily misdiagnosed as HCC especially on MR imaging with liver-specific contrast agent. Focal inflammatory liver lesions mimic HCC by demonstrating arterial-phase hypervascularity and subsequent washout on dynamic contrast-enhanced imaging. It is important to recognize the suggestive imaging findings for intrahepatic cholangiocarcinoma (CC) as the management of CC is largely different from that of HCC. There are other benign mimickers of HCC such as angiomyolipomas and focal nodular hyperplasia-like nodules. Recognition of their typical imaging findings can reduce false-positive HCC diagnosis. PMID:26770920

Dedifferentiated Liposarcoma Mimicking a Primary Colon Mass.

PubMed

Hollowoa, Blake; Lamps, Laura W; Mizell, Jason S; English, George W; Bridge, Julia A; Ram, Roopa; Gardner, Jerad M

2018-04-01

Dedifferentiated liposarcoma is typically a nonlipogenic high-grade sarcoma that arises from well-differentiated liposarcoma. It most commonly presents as a large mass in the retroperitoneum. Significant involvement of the gastrointestinal tract by dedifferentiated liposarcoma is uncommon. We present a unique case of dedifferentiated liposarcoma radiographically mimicking a primary colon mass with resulting intussusception; stranding of the adjacent adipose tissue was presumed to be a secondary reactive change. On histopathologic analysis of the hemicolectomy specimen, a high-grade sarcoma was seen growing through the colonic wall, and the majority of the surrounding pericolonic adipose tissue was actually composed of well-differentiated liposarcoma with characteristic fibrous bands rather than benign fat with reactive fibrosis. This case raises awareness that well-differentiated liposarcoma and dedifferentiated liposarcoma can rarely present as a primary intestinal mass mimicking colon cancer or other more common entities. When radiographic examination shows a perigastrointestinal or retroperitoneal fatty mass and/or stranding of the fat adjacent to a solid gastrointestinal mass, this unusual scenario should be considered in the radiologic differential diagnosis. Pathologists should keep dedifferentiated liposarcoma in the initial histologic differential diagnosis for any high-grade spindle cell tumor of the retroperitoneum or intra-abdominal visceral organs.

Morphologic mimickers of Cryptococcus occurring within inflammatory infiltrates in the setting of neutrophilic dermatitis: a series of three cases highlighting clinical dilemmas associated with a novel histopathologic pitfall.

PubMed

Ko, Jennifer S; Fernandez, Anthony P; Anderson, Kyle A; Burdick, Laura M; Billings, Steven D; Procop, Gary W; McMahon, James T; Bergfeld, Wilma F; Piliang, Melissa P

2013-01-01

A neutrophil-predominant inflammatory infiltrate in a cutaneous biopsy can be associated with a broad spectrum of diseases. Here we describe three cases showing a neutrophil-predominant dermal infiltrate admixed with abundant acellular bodies surrounded by capsule-like vacuolated spaces, which strikingly mimicked Cryptococcus. Two cases occurred within the settings of underlying hematologic malignancies; the third case was associated with immune dysregulation. Two patients were acutely ill in the medical intensive care unit. Fungal work-up, including cultures and multiple stains were negative. Because of clinical deterioration in these patients, transmission electron microscopy was pursued to definitively rule out fungal infection. In both cases, characteristics most compatible with autolysing human cells, not Cryptococcus, were identified. Chemotherapy and high-dose steroids were given, but both patients eventually succumbed to their diseases. To the best of our knowledge, these represent the first reported cases of autolysing human cells mimicking Cryptococcus organisms within neutrophilic infiltrates. They highlight the therapeutic dilemmas arising with histopathologic mimics, as well as the importance of thorough investigation to distinguish mimickers from true infectious organisms. We believe recognition of this microscopic pitfall will be useful to dermatopathologists faced with similar findings in the future, and may prevent unnecessary delay of appropriate therapy in acutely ill patients. Copyright © 2012 John Wiley & Sons A/S.

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.

Peroxidase-Mimicking Nanozyme with Enhanced Activity and High Stability Based on Metal-Support Interactions.

PubMed

Li, Zhihao; Yang, Xiangdong; Yang, Yanbing; Tan, Yaning; He, Yue; Liu, Meng; Liu, Xinwen; Yuan, Quan

2018-01-09

Peroxidase-mimicking nanozymes offer unique advantages in terms of high stability and low cost over natural peroxidase for applications in bioanalysis, biomedicine, and the treatment of pollution. However, the design of high-efficiency peroxidase-mimicking nanozymes remains a great challenge. In this study, we adopted a structural-design approach through hybridization of cube-CeO 2 and Pt nanoparticles to create a new peroxidase-mimicking nanozyme with high efficiency and excellent stability. Relative to pure cube-CeO 2 and Pt nanoparticles, the as-hybridized Pt/cube-CeO 2 nanocomposites display much improved activities because of the strong metal-support interaction. Meanwhile, the nanocomposites also maintain high catalytic activity after long-term storage and multiple recycling. Based on their excellent properties, Pt/cube-CeO 2 nanocomposites were used to construct high-performance colorimetric biosensors for the sensitive detection of metabolites, including H 2 O 2 and glucose. Our findings highlight opportunities for the development of high-efficiency peroxidase-mimicking nanozymes with potential applications such as diagnostics, biomedicine, and the treatment of pollution. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Activation of chronic toxoplasmosis by transportation stress in a mouse model.

PubMed

Shen, Bang; Yuan, Yuan; Cheng, Jianxi; Pan, Ming; Xia, Ningbo; Zhang, Weichao; Wang, Yifan; Zhou, Yanqin; Zhao, Junlong

2016-12-27

Toxoplasma gondii is an obligate intracellular parasite infecting 25% of the world population and enormous number of animals. It can exist in two forms in intermediate hosts: the fast replicating tachyzoites responsible for acute infection and the slowly replicating bradyzoites responsible for life-long chronic infection. The interconversion between tachyzoites and bradyzoites plays critical roles in the transmission and pathogenesis of T. gondii. However, the molecular mechanisms that govern the interconversion are largely unknown. In this study, we established a chronic infection model in mice and examined the impact of transportation stress on the status of chronic infection. Our results demonstrated that, treating chronically infected mice with conditions mimicking transportation stress reduced the levels of several key cytokines that restrict the infection at chronic stage. Increased expression of the tachyzoite specific gene SAG1 (surface antigen 1) was detected in brain cysts of stress treated mice, indicating activation and conversion of bradyzoites to tachyzoites. Using this model, we identified fifteen toxoplasmic proteins that had significant abundance changes during stress induced cysts reactivation. These proteins serve as a basis for further investigation of the mechanisms governing bradyzoite conversion.

Intramedullary dermoid cyst infection mimicking holocord tumor: should radical resection be mandatory?-a case report.

PubMed

Karaaslan, Burak; Ülkü, Göktuğ; Ucar, Murat; Demirdağ, Tuğba Bedir; İnan, Arda; Börcek, Alp Özgün

2016-11-01

Dermoid cysts are benign lesions which contain epidermal and dermal elements. Dermoid cysts usually contain a dermal sinus tract but this is not mandatory. Dermoid cysts can manifest by spinal cord infection without a dermal sinus tract. An infected spinal dermoid cyst associated with a holocord spinal abscess poses diagnostic and surgical challenges. Although radical surgical drainage is considered as the main treatment modality for spinal abscess, less extensive surgery for microbiological sampling and appropriate antibiotic treatment can be another alternative modality. A 1-year-old boy patient was admitted to our hospital with progressive paraplegia, bladder dysfunction, and neck rigidity. Medical history of the patient included recurrent urinary tract infection and cephalosporin treatments several times. Initial neurological examination revealed confusion, fever, neck rigidity, paraplegia (also, the motor power of the right upper extremity was three fifths that of the upper extremities). He had urinary and gastrointestinal retention. Conservative surgery was performed to take pathological and microbiological samples. With appropriate antibiotic regimen, the nuchal rigidity and fever improved dramatically. Infectious parameters in blood biochemistry significantly decreased after the antibiotic regimen. Holocord spinal abscesses are a rare entity. The source of the disease can be hemopoietic spread or contagious spread. The dermal sinus tract is major risk factor for contagious spread. The major hemopoietic sources are urogenital infection, endocarditis, and infective lung diseases. The hemopoietic spread is a more common source for pediatric patients. The thoracolumbar region is the most common site of involvement. Spinal infection has a tendency to extend longitudinally throughout spinal fibers. The pathogenesis of the holocord edema or syrinx is uncertain. The underlying etiology may be inflammation, infection, and associated venous congestion within the

Design, synthesis and DNA interactions of a chimera between a platinum complex and an IHF mimicking peptide.

PubMed

Rao, Harita; Damian, Mariana S; Alshiekh, Alak; Elmroth, Sofi K C; Diederichsen, Ulf

2015-12-28

Conjugation of metal complexes with peptide scaffolds possessing high DNA binding affinity has shown to modulate their biological activities and to enhance their interaction with DNA. In this work, a platinum complex/peptide chimera was synthesized based on a model of the Integration Host Factor (IHF), an architectural protein possessing sequence specific DNA binding and bending abilities through its interaction with a minor groove. The model peptide consists of a cyclic unit resembling the minor grove binding subdomain of IHF, a positively charged lysine dendrimer for electrostatic interactions with the DNA phosphate backbone and a flexible glycine linker tethering the two units. A norvaline derived artificial amino acid was designed to contain a dimethylethylenediamine as a bidentate platinum chelating unit, and introduced into the IHF mimicking peptides. The interaction of the chimeric peptides with various DNA sequences was studied by utilizing the following experiments: thermal melting studies, agarose gel electrophoresis for plasmid DNA unwinding experiments, and native and denaturing gel electrophoresis to visualize non-covalent and covalent peptide-DNA adducts, respectively. By incorporation of the platinum metal center within the model peptide mimicking IHF we have attempted to improve its specificity and DNA targeting ability, particularly towards those sequences containing adjacent guanine residues.

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.

Cystic Benign Metastasizing Leiomyoma of the Lung Mimicking Hydatid Cyst.

PubMed

Alimi, Faouzi; El Hadj Sidi, Chighali; Ghannouchi, Chams

2016-12-01

A 60-year-old woman, with history of a resected uterine benign leiomyoma, is operated for a cystic lesion in the left lung, mimicking an hydatid cyst, and confirmed histologically as Cystic Benign Metastasizing Leiomyoma.

Clinical and Histologic Mimickers of Celiac Disease.

PubMed

Kamboj, Amrit K; Oxentenko, Amy S

2017-08-17

Celiac disease is an autoimmune disorder of the small bowel, classically associated with diarrhea, abdominal pain, and malabsorption. The diagnosis of celiac disease is made when there are compatible clinical features, supportive serologic markers, representative histology from the small bowel, and response to a gluten-free diet. Histologic findings associated with celiac disease include intraepithelial lymphocytosis, crypt hyperplasia, villous atrophy, and a chronic inflammatory cell infiltrate in the lamina propria. It is important to recognize and diagnose celiac disease, as strict adherence to a gluten-free diet can lead to resolution of clinical and histologic manifestations of the disease. However, many other entities can present with clinical and/or histologic features of celiac disease. In this review article, we highlight key clinical and histologic mimickers of celiac disease. The evaluation of a patient with serologically negative enteropathy necessitates a carefully elicited history and detailed review by a pathologist. Medications can mimic celiac disease and should be considered in all patients with a serologically negative enteropathy. Many mimickers of celiac disease have clues to the underlying diagnosis, and many have a targeted therapy. It is necessary to provide patients with a correct diagnosis rather than subject them to a lifetime of an unnecessary gluten-free diet.

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

Epidermal cyst mimicking incision line metastasis.

PubMed

Gündoğdu, Ramazan; Ayhan, Erhan; Çolak, Tahsin

2017-01-01

Epidermal cysts are cystic tumors lined with keratinized squamous layer and filled with keratin debris. Epidermal cysts may develop by implantation of surface epidermal layer into the dermis or subcutaneous tissue after trauma or surgical procedures. Cervix cancer spreads either directly or via the vascular and lymphatic systems. Distant skin metastasis of endometrium or cervix cancer is very rare. In this case report, a patient who had a history of cervix cancer operation 11 years ago and presented with a mass that mimicked incision line metastasis and was histopathologically diagnosed with epidermal cyst is presented.

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.

Subependymal Heterotopia Mimicking Mass in Conventional Magnetic Resonance Imaging: Demonstration With 3T Advanced Neuroimages.

PubMed

Aktas, Filiz; Ogul, Hayri

2017-10-01

The authors reported a rare patient with large subependymal heterotopia mimicking cerebral neoplasia. A 22-year-old female was admitted with a history of right-sided paresthesia accompanied by progressive headache. Cerebral magnetic resonance (MR) imaging showed a large solid lesion in the left frontal lobe. Advanced MR images proved that the lesion was compatible with subependymal heterotopia. Large subependymal heterotopia may mimick cerebral neoplasia.

Friedreich's ataxia mimicking hereditary motor and sensory neuropathy.

PubMed

Panas, Marios; Kalfakis, Nikolaos; Karadima, Georgia; Davaki, Panagiota; Vassilopoulos, Demetris

2002-11-01

Four patients from three unrelated families, with clinical and electrophysiological findings compatible with the diagnosis of hereditary motor and sensory neuropathy, are presented. The molecular analysis showed that the affected individuals were homozygous for the mutation in the X25 gene, characteristic of Friedreich's ataxia. These patients seem to represent a form of Friedreich's ataxia mimicking Charcot-Marie-Tooth disease.

Central nervous system borreliosis mimicking a pontine tumour.

PubMed

Latsch, Kirsten; Tappe, Dennis; Warmuth-Metz, Monika; Hebestreit, Helge

2006-11-01

In childhood, facial nerve palsy and headache are typical symptoms of second and third stage neuroborreliosis. While focal demyelination is occasionally observed on MRI scans, the appearance of a tumorous lesion is extremely rare. The case of a 10-year-old girl with neuroborreliosis mimicking a space-occupying lesion in the brainstem, without any previously recognized manifestations of borreliosis, is reported.

Mitogen-activated protein kinases (MAPKs) regulate IL-6 over-production during concomitant influenza virus and Staphylococcus aureus infection.

PubMed

Klemm, Carolin; Bruchhagen, Christin; van Krüchten, Andre; Niemann, Silke; Löffler, Bettina; Peters, Georg; Ludwig, Stephan; Ehrhardt, Christina

2017-02-14

Bacterial super-infections are a major complication of influenza virus (IV) infections and often lead to severe pneumonia. One hallmark of IV-associated Staphylococcus aureus (S. aureus) infection is rapid progression to a serious disease outcome. Changes in immune and inflammatory host responses increase morbidity and complicate efficient therapy. A key player during inflammation is the multifunctional cytokine IL-6. Although increased IL-6 levels have been observed after severe disease upon IV and/or bacterial super-infection, the underlying molecular mechanisms still remain to be elucidated. In the present study, we focused on cellular signalling pathways regulating IL-6 production upon IV/S. aureus super-infection. Additionally, infection with viable bacteria was mimicked by lipoteichoic acid stimulation in this model. Analyses of cellular signalling mechanisms revealed synergistically increased activation of the MAPK p38 as well as enhanced phosphorylation of the MAPKs ERK1/2 and JNK in the presence of super-infecting bacteria. Interestingly, inhibition of MAPK activity indicated a strong dependence of IL-6 expression on p38 and ERK1/2, while the MAPK JNK seems not to be involved. Thus, our results provide new molecular insights into the regulation of IL-6, a marker of severe disease, which might contribute to the lethal synergism of IV and S. aureus.

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.

Nanosecond laser pulses for mimicking thermal effects on nanostructured tungsten-based materials

NASA Astrophysics Data System (ADS)

Besozzi, E.; Maffini, A.; Dellasega, D.; Russo, V.; Facibeni, A.; Pazzaglia, A.; Beghi, M. G.; Passoni, M.

2018-03-01

In this work, we exploit nanosecond laser irradiation as a compact solution for investigating the thermomechanical behavior of tungsten materials under extreme thermal loads at the laboratory scale. Heat flux factor thresholds for various thermal effects, such as melting, cracking and recrystallization, are determined under both single and multishot experiments. The use of nanosecond lasers for mimicking thermal effects induced on W by fusion-relevant thermal loads is thus validated by direct comparison of the thresholds obtained in this work and the ones reported in the literature for electron beams and millisecond laser irradiation. Numerical simulations of temperature and thermal stress performed on a 2D thermomechanical code are used to predict the heat flux factor thresholds of the different thermal effects. We also investigate the thermal effect thresholds of various nanostructured W coatings. These coatings are produced by pulsed laser deposition, mimicking W coatings in tokamaks and W redeposited layers. All the coatings show lower damage thresholds with respect to bulk W. In general, thresholds decrease as the porosity degree of the materials increases. We thus propose a model to predict these thresholds for coatings with various morphologies, simply based on their porosity degree, which can be directly estimated by measuring the variation of the coating mass density with respect to that of the bulk.

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.

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

Genome-wide transcriptome analysis of Clavibacter michiganensis subsp. michiganensis grown in xylem mimicking medium.

PubMed

Hiery, Eva; Adam, Susanne; Reid, Stephen; Hofmann, Jörg; Sonnewald, Sophia; Burkovski, Andreas

2013-12-01

The interaction between Clavibacter michiganensis subsp. michiganensis with its host, the tomato plant (Solanum lycopersicum), is poorly understood and only few virulence factors are known. While studying of the bacteria in planta is time-consuming and difficult, the analysis in vitro would facilitate research. Therefore, a xylem mimicking medium (XMM) for C. michiganensis subsp. michiganensis was established in this study based on an apoplast medium for Xanthomonas campestris pv. vesicatoria. In contrast to the apoplast medium, XMM contains no sugars, but amino acids which serve as nitrogen and carbon source. As a result, growth in XMM induced transcriptional changes of genes encoding putative sugar, amino acid and iron uptake systems. In summary, mRNA levels of about 8% of all C. michiganensis subsp. michiganensis genes were changed when XMM-grown bacteria were compared to M9 minimal medium-grown cells. Almost no transcriptional changes of genes encoding hydrolytic enzymes were detected, leading to the idea that XMM reflects the situation in the beginning of infection and therefore allows the characterization of virulence factors in this early stage of infection. The addition of the plant wound substance acetosyringone to the XMM medium led to a change in transcript amount, including genes coding for proteins involved in protein transport, iron uptake and regulation processes. Copyright © 2013 Elsevier B.V. All rights reserved.

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

Real-time monitoring of bacterial infection in vivo: development of bioluminescent staphylococcal foreign-body and deep-thigh-wound mouse infection models.

PubMed

Kuklin, Nelly A; Pancari, Gregory D; Tobery, Timothy W; Cope, Leslie; Jackson, Jesse; Gill, Charles; Overbye, Karen; Francis, Kevin P; Yu, Jun; Montgomery, Donna; Anderson, Annaliesa S; McClements, William; Jansen, Kathrin U

2003-09-01

Staphylococcal infections associated with catheter and prosthetic implants are difficult to eradicate and often lead to chronic infections. Development of novel antibacterial therapies requires simple, reliable, and relevant models for infection. Using bioluminescent Staphylococcus aureus, we have adapted the existing foreign-body and deep-wound mouse models of staphylococcal infection to allow real-time monitoring of the bacterial colonization of catheters or tissues. This approach also enables kinetic measurements of bacterial growth and clearance in each infected animal. Persistence of infection was observed throughout the course of the study until termination of the experiment at day 16 in a deep-wound model and day 21 in the foreign-body model, providing sufficient time to test the effects of antibacterial compounds. The usefulness of both animal models was assessed by using linezolid as a test compound and comparing bioluminescent measurements to bacterial counts. In the foreign-body model, a three-dose antibiotic regimen (2, 5, and 24 h after infection) resulted in a decrease in both luminescence and bacterial counts recovered from the implant compared to those of the mock-treated infected mice. In addition, linezolid treatment prevented the formation of subcutaneous abscesses, although it did not completely resolve the infection. In the thigh model, the same treatment regimen resulted in complete resolution of the luminescent signal, which correlated with clearance of the bacteria from the thighs.

Epidermal cyst mimicking incision line metastasis

PubMed Central

Gündoğdu, Ramazan; Ayhan, Erhan; Çolak, Tahsin

2017-01-01

Epidermal cysts are cystic tumors lined with keratinized squamous layer and filled with keratin debris. Epidermal cysts may develop by implantation of surface epidermal layer into the dermis or subcutaneous tissue after trauma or surgical procedures. Cervix cancer spreads either directly or via the vascular and lymphatic systems. Distant skin metastasis of endometrium or cervix cancer is very rare. In this case report, a patient who had a history of cervix cancer operation 11 years ago and presented with a mass that mimicked incision line metastasis and was histopathologically diagnosed with epidermal cyst is presented. PMID:28740968

Adefovir-Induced Hypophosphatemic Osteomalacia Mimicking Bone Metastases From Primary Hepatocarcinoma.

PubMed

Wei, Wei-Jun; Sun, Zhen-Kui; Shen, Chen-Tian; Qiu, Zhong-Ling; Luo, Quan-Yong

2017-09-01

Adefovir-induced hypophosphatemic osteomalacia in the context of hepatocarcinoma is rare and needs to be differentiated from metastatic hepatocarcinoma. We here report a case of severe osteomalacia whose focal uptakes of radiotracer on the Tc-MDP SPECT/CT images mimicked that of metastatic hepatocarcinoma.

Experimental Validation of ARFI Surveillance of Subcutaneous Hemorrhage (ASSH) Using Calibrated Infusions in a Tissue-Mimicking Model and Dogs.

PubMed

Geist, Rebecca E; DuBois, Chase H; Nichols, Timothy C; Caughey, Melissa C; Merricks, Elizabeth P; Raymer, Robin; Gallippi, Caterina M

2016-09-01

Acoustic radiation force impulse (ARFI) Surveillance of Subcutaneous Hemorrhage (ASSH) has been previously demonstrated to differentiate bleeding phenotype and responses to therapy in dogs and humans, but to date, the method has lacked experimental validation. This work explores experimental validation of ASSH in a poroelastic tissue-mimic and in vivo in dogs. The experimental design exploits calibrated flow rates and infusion durations of evaporated milk in tofu or heparinized autologous blood in dogs. The validation approach enables controlled comparisons of ASSH-derived bleeding rate (BR) and time to hemostasis (TTH) metrics. In tissue-mimicking experiments, halving the calibrated flow rate yielded ASSH-derived BRs that decreased by 44% to 48%. Furthermore, for calibrated flow durations of 5.0 minutes and 7.0 minutes, average ASSH-derived TTH was 5.2 minutes and 7.0 minutes, respectively, with ASSH predicting the correct TTH in 78% of trials. In dogs undergoing calibrated autologous blood infusion, ASSH measured a 3-minute increase in TTH, corresponding to the same increase in the calibrated flow duration. For a measured 5% decrease in autologous infusion flow rate, ASSH detected a 7% decrease in BR. These tissue-mimicking and in vivo preclinical experimental validation studies suggest the ASSH BR and TTH measures reflect bleeding dynamics. © The Author(s) 2015.

A theoretical and experimental investigation of nonlinear propagation of ultrasound through tissue mimicking media

NASA Astrophysics Data System (ADS)

Rielly, Matthew Robert

An existing numerical model (known as the Bergen code) is used to investigate finite amplitude ultrasound propagation through multiple layers of tissue-like media. This model uses a finite difference method to solve the nonlinear parabolic KZK wave equation. The code is modified to include an arbitrary frequency dependence of absorption and transmission effects for wave propagation across a plane interface at normal incidence. In addition the code is adapted to calculate the total intensity loss associated with the absorption of the fundamental and nonlinearly generated harmonics. Measurements are also taken of the axial nonlinear pressure field generated from a circular focused, 2.25 MHz source, through single and multiple layered tissue mimicking fluids, for source pressures in the range from 13 kPa to 310 kPa. Two tissue mimicking fluids are developed to provide acoustic properties similar to amniotic fluid and a typical soft tissue. The values of the nonlinearity parameter, sound velocity and frequency dependence of attenuation for both fluids are presented, and the measurement procedures employed to obtain these characteristics are described in detail. These acoustic parameters, together with the measured source conditions are used as input to the numerical model, allowing the experimental conditions to be simulated. Extensive comparisons are made between the model's predictions and the axial pressure field measurements. Results are presented in the frequency domain showing the fundamental and three subsequent harmonic amplitudes on axis, as a function of axial distance. These show that significant nonlinear distortion can occur through media with characteristics typical of tissue. Time domain waveform comparisons are also made. An excellent agreement is found between theory and experiment indicating that the model can be used to predict nonlinear ultrasound propagation through multiple layers of tissue-like media. The numerical code is also used to model the

SU-F-T-433: Evaluation of a New Dose Mimicking Application for Clinical Flexibility and Reliability

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

Hoffman, D; Nair, C Kumaran; Wright, C

2016-06-15

Purpose: Clinical workflow and machine down time occasionally require patients to be temporarily treated on a system other than the initial treatment machine. A new commercial dose mimicking application provides automated cross-platform treatment planning to expedite this clinical flexibility. The aim of this work is to evaluate the feasibility of automatic plan creation and establish a robust clinical workflow for prostate and pelvis patients. Methods: Five prostate and five pelvis patients treated with helical plans were selected for re-planning with the dose mimicking application, covering both simple and complex scenarios. Two-arc VMAT and 7- and 9-field IMRT plans were generatedmore » for each case, with the objective function of achieving similar dose volume histogram from the initial helical plans. Dosimetric comparisons include target volumes and organs at risk (OARs) (rectum, bladder, small bowel, femoral heads, etc.). Dose mimicked plans were evaluated by a radiation oncologist, and patient-specific QAs were performed to validate delivery. Results: Overall plan generation and transfer required around 30 minutes of dosimetrist’s time once the dose-mimicking protocol is setup for each site. The resulting VMAT and 7- and 9-field IMRT plans achieved equivalent PTV coverage and homogeneity (D99/DRx = 97.3%, 97.2%, 97.2% and HI = 6.0, 5.8, and 5.9, respectively), compared to helical plans (97.6% and 4.6). The OAR dose discrepancies were up to 6% in rectum Dmean, but generally lower in bladder, femoral heads, bowel and penile bulb. In the context of 1–5 fractions, the radiation oncologist evaluated the dosimetric changes as not clinically significant. All delivery QAs achieved >90% pass with a 3%/3mm gamma criteria. Conclusion: The automated dose-mimicking workflow offers a strategy to avoid missing treatment fractions due to machine down time with non-clinically significant changes in dosimetry. Future work will further optimize dose mimicking plans and

Acute Fulminant Uremic Neuropathy Following Coronary Angiography Mimicking Guillain-Barre Syndrome.

PubMed

Priti, Kumari; Ranwa, Bhanwar

2017-01-01

A 55-year-old diabetic woman suffered a posterior wall ST-elevation myocardial infarction. She developed contrast-induced nephropathy following coronary angiography. Acute fulminant uremic neuropathy was precipitated which initially mimicked Guillan-Barre Syndrome, hence reported.

A lethal disease model for New World hantaviruses using immunosuppressed Syrian hamsters.

PubMed

Vergote, Valentijn; Laenen, Lies; Vanmechelen, Bert; Van Ranst, Marc; Verbeken, Erik; Hooper, Jay W; Maes, Piet

2017-10-01

Hantavirus, the hemorrhagic causative agent of two clinical diseases, is found worldwide with variation in severity, incidence and mortality. The most lethal hantaviruses are found on the American continent where the most prevalent viruses like Andes virus and Sin Nombre virus are known to cause hantavirus pulmonary syndrome. New World hantavirus infection of immunocompetent hamsters results in an asymptomatic infection except for Andes virus and Maporal virus; the only hantaviruses causing a lethal disease in immunocompetent Syrian hamsters mimicking hantavirus pulmonary syndrome in humans. Hamsters, immunosuppressed with dexamethasone and cyclophosphamide, were infected intramuscularly with different New World hantavirus strains (Bayou virus, Black Creek Canal virus, Caño Delgadito virus, Choclo virus, Laguna Negra virus, and Maporal virus). In the present study, we show that immunosuppression of hamsters followed by infection with a New World hantavirus results in an acute disease that precisely mimics both hantavirus disease in humans and Andes virus infection of hamsters. Infected hamsters showed specific clinical signs of disease and moreover, histological analysis of lung tissue showed signs of pulmonary edema and inflammation within alveolar septa. In this study, we were able to infect immunosuppressed hamsters with different New World hantaviruses reaching a lethal outcome with signs of disease mimicking human disease.

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

The Stochastic Multi-strain Dengue Model: Analysis of the Dynamics

NASA Astrophysics Data System (ADS)

Aguiar, Maíra; Stollenwerk, Nico; Kooi, Bob W.

2011-09-01

Dengue dynamics is well known to be particularly complex with large fluctuations of disease incidences. An epidemic multi-strain model motivated by dengue fever epidemiology shows deterministic chaos in wide parameter regions. The addition of seasonal forcing, mimicking the vectorial dynamics, and a low import of infected individuals, which is realistic in the dynamics of infectious diseases epidemics show complex dynamics and qualitatively a good agreement between empirical DHF monitoring data and the obtained model simulation. The addition of noise can explain the fluctuations observed in the empirical data and for large enough population size, the stochastic system can be well described by the deterministic skeleton.

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.

Heparin-mimicking multilayer coating on polymeric membrane via LbL assembly of cyclodextrin-based supramolecules.

PubMed

Deng, Jie; Liu, Xinyue; Ma, Lang; Cheng, Chong; Shi, Wenbin; Nie, Chuanxiong; Zhao, Changsheng

2014-12-10

In this study, multifunctional and heparin-mimicking star-shaped supramolecules-deposited 3D porous multilayer films with improved biocompatibility were fabricated via a layer-by-layer (LbL) self-assembly method on polymeric membrane substrates. Star-shaped heparin-mimicking polyanions (including poly(styrenesulfonate-co-sodium acrylate; Star-PSS-AANa) and poly(styrenesulfonate-co-poly(ethylene glycol)methyl ether methacrylate; Star-PSS-EGMA)) and polycations (poly(methyl chloride-quaternized 2-(dimethylamino)ethyl methacrylate; Star-PMeDMA) were first synthesized by atom transfer radical polymerization (ATRP) from β-cyclodextrin (β-CD) based cores. Then assembly of 3D porous multilayers onto polymeric membrane surfaces was carried out by alternating deposition of the polyanions and polycations via electrostatic interaction. The surface morphology and composition, water contact angle, blood activation, and thrombotic potential as well as cell viability for the coated heparin-mimicking films were systematically investigated. The results of surface ATR-FTIR spectra and XPS spectra verified successful deposition of the star-shaped supramolecules onto the biomedical membrane surfaces; scanning electron microscopy (SEM) and atomic force microscopy (AFM) observations revealed that the modified substrate had 3D porous surface morphology, which might have a great biological influence on the biointerface. Furthermore, systematic in vitro investigation of protein adsorption, platelet adhesion, human platelet factor 4 (PF4, indicates platelet activation), activate partial thromboplastin time (APTT), thrombin time (TT), coagulation activation (thrombin-antithrombin III complex (TAT, indicates blood coagulant)), and blood-related complement activation (C3a and C5a, indicates inflammation potential) confirmed that the heparin-mimicking multilayer coated membranes exhibited ultralow blood component activations and excellent hemocompatibility. Meanwhile, after surface coating

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.

Tuberculous temporal brain abscess mimicking otogenic pyogenic abscess.

PubMed

Muzumdar, D; Balasubramaniam, S; Melkundi, S

2009-01-01

Tuberculous brain abscess is a rare manifestation of central nervous system tuberculosis. We report the case of a tuberculous temporal lobe abscess in a 14-year-old female child that mimicked an otogenic pyogenic brain abscess. The patient had no prior history of tuberculosis. She had chronic otitis media and presented with signs of raised intracranial tension. Radiological imaging was suggestive of an acute pyogenic left temporal lobe abscess. A left temporal craniotomy was performed and the abscess was completely excised. Histological examination was consistent with a chronic abscess, and bacterial cultures were negative. A left radical mastoidectomy was also carried out. However, she presented with repeated abscess formation at the same site over the next 8 weeks, which was refractory to surgical therapy and broad-spectrum antibiotic administration. Furthermore, the purulent exudate showed strong positivity in the PCR test for tubercular bacilli. After administration of antituberculous treatment, she showed gradual clinical and radiological improvement. At follow-up after 2 years, she is asymptomatic. CT imaging at 2 years showed total resolution of abscess. Tuberculous abscess in the temporal lobe following otogenic infection has not been reported in the pediatric population. Although rare, the possibility of tuberculous etiology should be borne in mind as a differential diagnosis of acute abscess of otogenic origin, especially in endemic areas where the incidence of chronic otitis media as well as tuberculosis is high. The pathogenesis and treatment of tuberculous brain abscess in children is reviewed in light of the current literature on the subject. Copyright 2009 S. Karger AG, Basel.

Neglected foreign body aspiration mimicking bronchial carcinoma.

PubMed

Afghani, Reza; Khandashpour Ghomi, Mahmoud; Khandoozi, Seyed Reza; Yari, Behrouz

2016-07-01

Foreign body aspiration can occur in any age group, but it is more commonly seen in children. In adults, there is usually a predisposing condition that poses a risk of aspiration. If aspiration occurs, prompt diagnosis and extraction of the foreign body is needed to prevent early and late complications. We report a rare case of neglected foreign body aspiration in a 45-year-old schizophrenic opium addicted patient, which resulted in an occlusive lesion in the bronchus, mimicking bronchial carcinoma. © The Author(s) 2016.

Reticulated acanthoma with sebaceous differentiation mimicking melanoma

PubMed Central

Ribeiro, Felipe; Leocadia, Elizabeth; Macarenco, Ricardo S.; Lapins, Jan; Huet, Pascale; Akay, Bengu Nisa; Steiner, Denise

2017-01-01

Reticulated acanthoma with sebaceous differentiation (RASD) is a rare, benign cutaneous tumor with peculiar histopathologic characteristics [1]. RASD had been described under various synonyms such as superficial epithelioma with sebaceous differentiation, sebocrine adenoma, poroma with sebaceous differentiation, and seborrheic keratosis with sebaceous differentiation [2]. Clinical differential diagnosis of RASD includes cutaneous superficial epithelial neoplasia such as Bowen’s disease, superficial basal cell carcinoma (BCC) and intraepidermal eccrine poroma [1]. We report the first case of RASD mimicking both clinically and dermoscopically a melanoma. PMID:29085717

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.

Nerve cell-mimicking liposomes as biosensor for botulinum neurotoxin complete physiological activity

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

Weingart, Oliver G., E-mail: Oliver.Weingart@hest.

Botulinum neurotoxins (BoNT) are the most toxic substances known, and their neurotoxic properties and paralysing effects are exploited for medical treatment of a wide spectrum of disorders. To accurately quantify the potency of a pharmaceutical BoNT preparation, its physiological key activities (binding to membrane receptor, translocation, and proteolytic degradation of SNARE proteins) need to be determined. To date, this was only possible using animal models, or, to a limited extent, cell-based assays. We here report a novel in vitro system for BoNT/B analysis, based on nerve-cell mimicking liposomes presenting motoneuronal membrane receptors required for BoNT binding. Following triggered membrane translocationmore » of the toxin's Light Chain, the endopeptidase activity can be quantitatively monitored employing a FRET-based reporter assay within the functionalized liposomes. We were able to detect BoNT/B physiological activity at picomolar concentrations in short time, opening the possibility for future replacement of animal experimentation in pharmaceutical BoNT testing. - Highlights: • A cell-free in vitro system was used to measure BoNT/B physiological function. • The system relies on nerve-cell mimicking liposomes as a novel detection system. • A FRET-based reporter assay is used as final readout of the test system. • BoNT/B physiological activity was detected at picogram quantities in short time. • The method opens the possibility to replace animal experimentation in BoNT testing.« less

Demodex folliculitis mimicking acute graft-vs-host disease.

PubMed

Cotliar, Jonathan; Frankfurt, Olga

2013-12-01

Acute graft-vs-host disease (GVHD) typically requires high-dose systemic steroids as first-line treatment. Like drug eruptions, viral exanthema, and toxic erythema of chemotherapy, Demodex folliculitis is a clinical mimicker of acute GVHD and requires nonimmunosuppressive therapy. This case of Demodex folliculitis mimicking acute GVHD highlights the need for skin biopsy in patients who have undergone a stem cell transplant with eruptions on the head and neck. A 46-year-old white woman with a history of Fms-like tyrosine kinase 3 acute myeloid leukemia presented to the dermatology clinic with a 5-day history of a nonpruritic eruption on her face and neck 28 days after undergoing a double umbilical cord blood hematopoietic stem cell transplant (HSCT). Findings from the skin biopsy demonstrated a deep dermal lymphocytic infiltrate adjacent to follicular units along with an abundance of Demodex mites noted within the hair follicles consistent with Demodex folliculitis. Oral ivermectin, 12 mg, was given, and the eruption cleared within 24 hours. To our knowledge, this is only the fifth reported case of Demodex folliculitis following HSCT, but the first ever reported to be successfully treated with oral ivermectin. Demodex folliculitis should be added to the differential diagnosis of skin eruptions that arise after HSCT.

Infected intraparenchymal bronchogenic cyst mimicking recurrent lung abscess in a young adult.

PubMed

Ramzisham, A R M; Johann, K F; Talal, A R; Joanna, O S M; Zamrin, D M

2007-12-01

A 23 year old female with a past history of a lung abscess diagnosed at the age of 13 years presented with recurrent episodes of productive cough. Chest radiograph and a high resolution CT scan of the thorax led to the diagnosis of a left lower lobe lung abscess. She underwent a successful thoracotomy and a left lower lobe lobectomy. Histopathological examination revealed the diagnosis of an infected congenital bronchogenic cyst. The recent literature on this is reviewed.

Acute Fulminant Uremic Neuropathy Following Coronary Angiography Mimicking Guillain–Barre Syndrome

PubMed Central

Priti, Kumari; Ranwa, Bhanwar

2017-01-01

A 55-year-old diabetic woman suffered a posterior wall ST-elevation myocardial infarction. She developed contrast-induced nephropathy following coronary angiography. Acute fulminant uremic neuropathy was precipitated which initially mimicked Guillan–Barre Syndrome, hence reported. PMID:28706599

Fibromatosis of the breast mimicking an abscess: case report of unusual sonographic features.

PubMed

Lee, So Min; Lee, Ji Young; Lee, Byung Hoon; Kim, Su Young; Joo, Mee; Kim, Jae Il

2015-01-01

Fibromatosis of the breast, also known as a desmoid tumor, is extremely rare and most often appears as an aggressive lesion mimicking breast carcinoma. It lacks metastatic potential but can grow aggressively in a localized area. Ultrasonography often shows an irregular spiculated hypoechoic mass with posterior acoustic shadowing. We discuss a case of breast fibromatosis that presented as a painful palpable breast mass in a 32-year-old woman and mimicked an abscess in the sonogram. We found that this lesion displayed atypical sonographic features such as a heterogeneous echoic mass with an internal anechoic area. Copyright © 2015 Elsevier Inc. All rights reserved.

Subdural Hematoma Mimickers: A Systematic Review.

PubMed

Catana, Dragos; Koziarz, Alex; Cenic, Aleksa; Nath, Siddharth; Singh, Sheila; Almenawer, Saleh A; Kachur, Edward

2016-09-01

A variety of subdural pathologies that may mimic hematomas are reported in the literature. We aimed to identify the atypical clinical and radiologic presentations of subdural masses that may mimic subdural hematomas. A systematic review of MEDLINE and Embase was conducted independently by 2 reviewers to identify articles describing subdural hematoma mimickers. We also present a patient from our institution with a subdural pathology mimicking a subdural hematoma. We analyzed patient clinical presentations, underlying pathologies, radiologic findings, and clinical outcomes. We included 43 articles totaling 48 patients. The mean ± SD patient age was 55.7 ± 16.8 years. Of the 45 cases describing patient history, 13 patients (27%) had a history of trauma. The underlying pathologies of the 48 subdural collections were 10 metastasis (21%), 14 lymphoma (29%), 7 sarcoma (15%), 4 infectious (8%), 4 autoimmune (8%), and 9 miscellaneous (19%). Findings on computed tomography (CT) scan were 18 hyperdense (41%), 11 hypodense (25%), 9 isodense (20%), 3 isodense/hyperdense (7%), and 3 hypodense/isodense (7%). Thirty-four patients (71%) were treated surgically; among these patients, 65% had symptom resolution. Neither the pathology (P = 0.337) nor the management strategy (P = 0.671) was correlated with improved functional outcomes. Identification of atypical history and radiologic features should prompt further diagnostic tests, including magnetic resonance imaging (MRI), to elucidate the proper diagnosis, given that certain pathologies may be managed nonsurgically. A subdural collection that is hyperdense on CT scan and hyperintense on T2-weighted MRI, along with a history of progressive headache with no trauma, may raise the suspicion of an atypical subdural pathology. Copyright © 2016 Elsevier Inc. All rights reserved.

Validation of a sensitive DNA walking strategy to characterise unauthorised GMOs using model food matrices mimicking common rice products.

PubMed

Fraiture, Marie-Alice; Herman, Philippe; Taverniers, Isabel; De Loose, Marc; Van Nieuwerburgh, Filip; Deforce, Dieter; Roosens, Nancy H

2015-04-15

To identify unauthorised GMOs in food and feed matrices, an integrated approach has recently been developed targeting pCAMBIA family vectors, highly present in transgenic plants. Their presence is first assessed by qPCR screening and is subsequently confirmed by characterising the transgene flanking regions, using DNA walking. Here, the DNA walking performance has been thoroughly tested for the first time, regarding the targeted DNA quality and quantity. Several assays, on model food matrices mimicking common rice products, have allowed to determine the limit of detection as well as the potential effects of food mixture and processing. This detection system allows the identification of transgenic insertions as low as 10 HGEs and was not affected by the presence of untargeted DNA. Moreover, despite the clear impact of food processing on DNA quality, this method was able to cope with degraded DNA. Given its specificity, sensitivity, reliability, applicability and practicability, the proposed approach is a key detection tool, easily implementable in enforcement laboratories. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Neoplastic stomach lesions and their mimickers: spectrum of imaging manifestations

PubMed Central

Virmani, Vivek; Sethi, Vineeta; Fraser-Hill, Margret; Fasih, Najla; Kielar, Ania

2012-01-01

Abstract This review illustrates a wide spectrum of gastric neoplasms with emphasis on imaging findings helpful in characterizing various gastric neoplasms. Both the malignant and benign neoplasms along with focal gastric masses mimicking tumour are illustrated. Moreover, imaging clues to reach an accurate diagnosis are emphasized. PMID:22935192

Primary Papillary Mucinous Adenocarcinoma of the Ureter Mimicking Genitourinary Tuberculosis

PubMed Central

Gulwani, Hanni; Jain, Aruna

2010-01-01

Primary adenocarcinomas of the renal pelvis and ureter are rare and account for less than 1% of all malignancies at this site. We report a case of primary papillary mucinous adenocarcinoma of the ureter that clinically mimicked genitourinary tuberculosis. Early diagnosis is important for the better outcome. PMID:21151719

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.

Proposed Pharmacological Countermeasures Against Apoptotic Cell Death in Experimental Models Mimicking Space Environment Damage

NASA Astrophysics Data System (ADS)

Lulli, Matteo; Papucci, Laura; Witort, Ewa; Donnini, Martino; Lapucci, Andrea; Lazzarano, Stefano; Mazzoni, Tiziano; Simoncini, Madine; Falciani, Piergiuseppe; Capaccioli, Sergio

2008-06-01

Several damaging agents have been suggested to affect human vision during long term space travels. Recently, apoptosis induced by DNA-damaging agents has emerged as frequent pathogenetic mechanism of ophthalmologic pathologies. Here, we propose two countermeasures: coenzyme Q10 and bcl-2 downregulation preventing antisense oligoribonucleotides (ORNs), aimed to inhibit cellular apoptotic death. Our studies have been carried out on retina and neuronal cultured cells treated with the following apoptotic stimuli mimicking space environment: a several-day exposure to either 3H-labeled tymidine or to the genotoxic drug doxorubicin, UV irradiation, hypoxia and glucose/growth factor starvation (Locke medium). The preliminary results clearly indicate that CoQ10, as well as bcl-2 down-regulation preventing ORNs, significantly counteract apoptosis in response to different DNA damaging agents in cultured eye and in neuronal cells. This supports the possibility that both could be optimal countermeasures against ophthalmologic lesions during space explorations.

Post-pancreatitis Fat Necrosis Mimicking Carcinomatosis.

PubMed

Smith, Joshua P; Arnoletti, J Pablo; Varadarajulu, Shyam; Morgan, Desiree E

2008-01-01

Acute pancreatitis can result in retroperitoneal fat necrosis, typically occurring in the peripancreatic region, with extension into the transverse mesocolon, omentum and mesenteric root. When evaluated with contrast enhanced computed tomography (CECT), acute peripancreatic post necrotic collections typically become lower in attenuation over time, and often appear as homogeneous fluid collections. Saponification as a complication of fat necrosis in patients with acute pancreatitis is a well recognized clinical entity. While retroperitonal fat necrosis is commonly seen on CECT, saponification is not a prominent imaging feature. We present a case of acute pancreatitis complicated by extensive saponification of fat throughout the retroperitoneum and peritoneal lining, mimicking carcinomatosis.

Cogan's syndrome mimicking acute Lyme arthritis.

PubMed

Schwegmann, J P; Enzenauer, R J

1995-05-01

A pediatric case of Cogan's syndrome mimicking acute Lyme arthritis is described. A 12-year-old black boy was admitted to the pediatric service for presumed right knee septic arthritis. Symptoms included acute pain and swelling with decreased range-of-motion. Although the patient's right knee symptoms and positive Lyme serology were consistent with a diagnosis of Lyme arthritis, the presence of sensorineural hearing loss and interstitial keratitis with inflammatory arthritis suggested a diagnosis of Cogan's syndrome. Subsequent Western blot analysis was negative for Borrelia burgdorferi antigens. The patient had dramatic clinical improvement of musculoskeletal and ophthalmologic complaints shortly after receiving high-dose corticosteroids, although residual sensorineural hearing loss persisted.

Toxicology Analysis of Tissue-Mimicking Phantom Made From Gelatin

NASA Astrophysics Data System (ADS)

Dolbashid, A. S.; Hamzah, N.; Zaman, W. S. W. K.; Mokhtar, M. S.

2017-06-01

Skin phantom mimics the biological skin tissues as it have the ability to respond to changes in its environment. The development of tissue-mimicking phantom could contributes towards the reduce usage of animal in cosmetics and pharmacokinetics. In this study, the skin phantoms made from gelatin were tested with four different commonly available cosmetic products to determine the toxicity of each substance. The four substances used were; mercury-based whitening face cream, carcinogenic liquid make-up foundation, paraben-based acne cleanser, and organic lip balm. Toxicity test were performed on all of the phantoms. For toxicity testing, topographical and electrophysiological changes of the phantoms were evaluated. The ability of each respective phantom to react with mild toxic substances and its electrical resistance were analysed in to determine the toxicity of all the phantom models. Four-electrode method along with custom made electrical impedance analyser was used to differentiate electrical resistance between intoxicated phantom and non-intoxicated phantom in this study. Electrical resistance values obtained from the phantom models were significantly higher than the control group. The result obtained suggests the phantom as a promising candidate to be used as alternative for toxicology testing in the future.

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.

Being Mimicked Increases Prosocial Behavior in 18-Month-Old Infants

ERIC Educational Resources Information Center

Carpenter, Malinda; Uebel, Johanna; Tomasello, Michael

2013-01-01

Most previous research on imitation in infancy has focused on infants' learning of instrumental actions on objects. This study focused instead on the more social side of imitation, testing whether being mimicked increases prosocial behavior in infants, as it does in adults (van Baaren, Holland, Kawakami, & van Knippenberg, 2004).…

Fatal chronic active Epstein-Barr virus infection mimicking autoimmune hepatitis.

PubMed

Chiba, Tetsuhiro; Goto, Shigemasa; Yokosuka, Osamu; Imazeki, Fumio; Tanaka, Masamichi; Fukai, Kenichi; Takahashi, Yoko; Tsujimura, Hideki; Saisho, Hiromitsu

2004-02-01

We report a 22-year-old female who presented with pyrexia, pancytopenia and liver dysfunction. The patient showed mild liver dysfunction with low-grade fever and mild hepatosplenomegaly 6 years previously, and autoimmune hepatitis (AIH) was diagnosed based on the examination of the laboratory data and liver biopsy. On admission, both markers of Epstein-Barr virus (EBV) and in-situ hybridisation from a liver biopsy specimen indicated chronic active EBV infection (CAEBV). The patient was administered an immunosuppressive agent and antiviral drug added to steroid therapy, but ultimately died from liver failure and virus-associated haemophagocytosis 10 months after the definite diagnosis. Retrospective examination of the serum at the diagnosis of AIH revealed extremely high titres of antibody to EBV, and EBV-DNA was also detectable by polymerase chain reaction. These results suggest the possibility that the patient may already have suffered from CAEBV at the initial diagnosis. We presume that hepatic involvement of CAEBV should be considered as differential diagnosis in cases showing liver dysfunction with clinical and biochemical features observed in AIH.

Can the route of Toxoplasma gondii infection affect the ophthalmic outcomes?

PubMed

Ashour, Dalia S; Saad, Abeer E; Bakary, Reda H El; Barody, Mohamed A El

2018-06-14

Ocular toxoplasmosis is the most common cause of retinochoroiditis worldwide in humans. Some studies highlighted the idea that ocular lesions differ according to the route of infection but none of them mimicked the natural route. The current study aimed to investigate the ophthalmic outcomes in congenital and oral routes of infection with Toxoplasma in experimental animals. Mice were divided into three groups; group I: congenital infection, group II: acquired oral infection and group III: non-infected. We used Me49 chronic low-virulence T. gondii strain. We found that retina is the most affected part in both modes of infections. However, the retinal changes are different and more pronounced in case of congenital infection. The congenitally infected mice showed retinal lesions e.g. total detachment of retinal pigment epithelium from the photoreceptor layer and irregular arrangement of retinal layers. More severe damage was observed in mice infected early in pregnancy. While the postnatal orally infected mice showed fewer changes. In conclusion, the routes of Toxoplasma infection affect the ophthalmic outcomes and this may be the case in human disease. Although both are vision threatening, it seems that the prognosis of postnatal acquired ocular toxoplasmosis is better than that of congenital disease.

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

Mimicking the Moon

NASA Image and Video Library

2014-11-03

When Galileo first observed Venus displaying a crescent phase, he excitedly wrote to Kepler (in anagram) of Venus mimicking the moon-goddess. He would have been delirious with joy to see Saturn and Titan, seen in this image, doing the same thing. More than just pretty pictures, high-phase observations -- taken looking generally toward the Sun, as in this image -- are very powerful scientifically since the way atmospheres and rings transmit sunlight is often diagnostic of compositions and physical states. In this example, Titan's crescent nearly encircles its disk due to the small haze particles high in its atmosphere refracting the incoming light of the distant Sun. This view looks toward the sunlit side of the rings from about 3 degrees above the ringplane. The image was taken in violet light with the Cassini spacecraft wide-angle camera on Aug. 11, 2013. The view was obtained at a distance of approximately 1.1 million miles (1.7 million kilometers) from Saturn and at a Sun-Saturn-spacecraft, or phase, angle of 154 degrees. Image scale is 64 miles (103 kilometers) per pixel. http://photojournal.jpl.nasa.gov/catalog/PIA18291

Moderately nonlinear ultrasound propagation in blood-mimicking fluid.

PubMed

Kharin, Nikolay A; Vince, D Geoffrey

2004-04-01

In medical diagnostic ultrasound (US), higher than-in-water nonlinearity of body fluids and tissue usually does not produce strong nonlinearly distorted waves because of the high absorption. The relative influence of absorption and nonlinearity can be characterized by the Gol'dberg number Gamma. There are two limiting cases in nonlinear acoustics: weak waves (Gamma < 1) or strong waves (Gamma > 1). However, at diagnostic frequencies in tissue and body fluids, the nonlinear effects and effects of absorption more likely are comparable (Gol'dberg number Gamma approximately 1). The aim of this work was to study the nonlinear propagation of a moderately nonlinear US second harmonic signal in a blood-mimicking fluid. Quasilinear solutions to the KZK equation are presented, assuming radiation from a flat and geometrically focused circular Gaussian source. The solutions are expressed in a new simplified closed form and are in very good agreement with those of previous studies measuring and modeling Gaussian beams. The solutions also show good agreement with the measurements of the beams produced by commercially available transducers, even without special Gaussian shading.

Cerebral Toxoplasmosis Mimicking Subacute Meningitis in HIV-Infected Patients; a Cohort Study from Indonesia

PubMed Central

Ganiem, A. Rizal; Dian, Sofiati; Indriati, Agnes; Chaidir, Lidya; Wisaksana, Rudi; Sturm, Patrick; Melchers, Willem; van der Ven, Andre; Parwati, Ida; van Crevel, Reinout

2013-01-01

Background HIV-associated subacute meningitis is mostly caused by tuberculosis or cryptococcosis, but often no etiology can be established. In the absence of CT or MRI of the brain, toxoplasmosis is generally not considered as part of the differential diagnosis. Methodology/Principal Findings We performed cerebrospinal fluid real time PCR and serological testing for Toxoplasma gondii in archived samples from a well-characterized cohort of 64 HIV-infected patients presenting with subacute meningitis in a referral hospital in Indonesia. Neuroradiology was only available for 6 patients. At time of presentation, patients mostly had newly diagnosed and advanced HIV infection (median CD4 count 22 cells/mL), with only 17.2% taking ART, and 9.4% PJP-prophylaxis. CSF PCR for T. Gondii was positive in 21 patients (32.8%). Circulating toxoplasma IgG was present in 77.2% of patients tested, including all in whom the PCR of CSF was positive for T. Gondii. Clinically, in the absence of neuroradiology, toxoplasmosis was difficult to distinguish from tuberculosis or cryptococcal meningitis, although CSF abnormalities were less pronounced. Mortality among patients with a positive CSF T. Gondii PCR was 81%, 2.16-fold higher (95% CI 1.04–4.47) compared to those with a negative PCR. Conclusions/Significance Toxoplasmosis should be considered in HIV-infected patients with clinically suspected subacute meningitis in settings where neuroradiology is not available. PMID:23326616

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.

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.

The cutaneous manifestations and common mimickers of physical child abuse.

PubMed

Mudd, Shawna S; Findlay, Jeanne S

2004-01-01

The cutaneous manifestations of physical child abuse are some of the most common and easily recognized forms of injury. To make an accurate assessment and diagnosis, it is important to differentiate between inflicted cutaneous injuries and mimickers of physical abuse. Likewise, an understanding of reporting guidelines helps guide practitioners in their decision making.

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.

Congruent Strain Specific Intestinal Persistence of Lactobacillus plantarum in an Intestine-Mimicking In Vitro System and in Human Volunteers

PubMed Central

van Bokhorst-van de Veen, Hermien; van Swam, Iris; Wels, Michiel; Bron, Peter A.; Kleerebezem, Michiel

2012-01-01

Background An important trait of probiotics is their capability to reach their intestinal target sites alive to optimally exert their beneficial effects. Assessment of this trait in intestine-mimicking in vitro model systems has revealed differential survival of individual strains of a species. However, data on the in situ persistence characteristics of individual or mixtures of strains of the same species in the gastrointestinal tract of healthy human volunteers have not been reported to date. Methodology/Principal Findings The GI-tract survival of individual L. plantarum strains was determined using an intestine mimicking model system, revealing substantial inter-strain differences. The obtained data were correlated to genomic diversity of the strains using comparative genome hybridization (CGH) datasets, but this approach failed to discover specific genetic loci that explain the observed differences between the strains. Moreover, we developed a next-generation sequencing-based method that targets a variable intergenic region, and employed this method to assess the in vivo GI-tract persistence of different L. plantarum strains when administered in mixtures to healthy human volunteers. Remarkable consistency of the strain-specific persistence curves were observed between individual volunteers, which also correlated significantly with the GI-tract survival predicted on basis of the in vitro assay. Conclusion The survival of individual L. plantarum strains in the GI-tract could not be correlated to the absence or presence of specific genes compared to the reference strain L. plantarum WCFS1. Nevertheless, in vivo persistence analysis in the human GI-tract confirmed the strain-specific persistence, which appeared to be remarkably similar in different healthy volunteers. Moreover, the relative strain-specific persistence in vivo appeared to be accurately and significantly predicted by their relative survival in the intestine-mimicking in vitro assay, supporting the

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.

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.

Absolute backscatter coefficient estimates of tissue-mimicking phantoms in the 5–50 MHz frequency range

PubMed Central

McCormick, Matthew M.; Madsen, Ernest L.; Deaner, Meagan E.; Varghese, Tomy

2011-01-01

Absolute backscatter coefficients in tissue-mimicking phantoms were experimentally determined in the 5–50 MHz frequency range using a broadband technique. A focused broadband transducer from a commercial research system, the VisualSonics Vevo 770, was used with two tissue-mimicking phantoms. The phantoms differed regarding the thin layers covering their surfaces to prevent desiccation and regarding glass bead concentrations and diameter distributions. Ultrasound scanning of these phantoms was performed through the thin layer. To avoid signal saturation, the power spectra obtained from the backscattered radio frequency signals were calibrated by using the signal from a liquid planar reflector, a water-brominated hydrocarbon interface with acoustic impedance close to that of water. Experimental values of absolute backscatter coefficients were compared with those predicted by the Faran scattering model over the frequency range 5–50 MHz. The mean percent difference and standard deviation was 54% ± 45% for the phantom with a mean glass bead diameter of 5.40 μm and was 47% ± 28% for the phantom with 5.16 μm mean diameter beads. PMID:21877789

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.

Autoimmune pancreatitis associated with renal lesions mimicking metastatic tumours

PubMed Central

Rudmik, Lucas; Trpkov, Kiril; Nash, Carla; Kinnear, Susan; Falck, Vincent; Dushinski, John; Dixon, Elijah

2006-01-01

Autoimmune pancreatitis is a chronic inflammatory disorder that is often misdiagnosed as pancreatic cancer. Since autoimmune pancreatitis is benign and responds to steroid management, it is important to diagnose it to avoid unnecessary surgical intervention. We describe a novel case of IgG4-associated autoimmune pancreatitis presenting with tubulointerstitial nephritis as renal lesions mimicking metastatic tumours but with no change in renal function. PMID:16908897

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.

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

Multilayered tissue mimicking skin and vessel phantoms with tunable mechanical, optical, and acoustic properties

PubMed Central

Chen, Alvin I.; Balter, Max L.; Chen, Melanie I.; Gross, Daniel; Alam, Sheikh K.; Maguire, Timothy J.; Yarmush, Martin L.

2016-01-01

Purpose: This paper describes the design, fabrication, and characterization of multilayered tissue mimicking skin and vessel phantoms with tunable mechanical, optical, and acoustic properties. The phantoms comprise epidermis, dermis, and hypodermis skin layers, blood vessels, and blood mimicking fluid. Each tissue component may be individually tailored to a range of physiological and demographic conditions. Methods: The skin layers were constructed from varying concentrations of gelatin and agar. Synthetic melanin, India ink, absorbing dyes, and Intralipid were added to provide optical absorption and scattering in the skin layers. Bovine serum albumin was used to increase acoustic attenuation, and 40 μm diameter silica microspheres were used to induce acoustic backscatter. Phantom vessels consisting of thin-walled polydimethylsiloxane tubing were embedded at depths of 2–6 mm beneath the skin, and blood mimicking fluid was passed through the vessels. The phantoms were characterized through uniaxial compression and tension experiments, rheological frequency sweep studies, diffuse reflectance spectroscopy, and ultrasonic pulse-echo measurements. Results were then compared to in vivo and ex vivo literature data. Results: The elastic and dynamic shear behavior of the phantom skin layers and vessel wall closely approximated the behavior of porcine skin tissues and human vessels. Similarly, the optical properties of the phantom tissue components in the wavelength range of 400–1100 nm, as well as the acoustic properties in the frequency range of 2–9 MHz, were comparable to human tissue data. Normalized root mean square percent errors between the phantom results and the literature reference values ranged from 1.06% to 9.82%, which for many measurements were less than the sample variability. Finally, the mechanical and imaging characteristics of the phantoms were found to remain stable after 30 days of storage at 21 °C. Conclusions: The phantoms described in this

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.

Programmable Control in Extracellular Matrix-mimicking Polymer Hydrogels.

PubMed

Hof, Kevin S; Bastings, Maartje M C

2017-06-28

The extracellular matrix (ECM) and cells have a reciprocal relationship, one shapes the other and vice versa. One of the main challenges of synthetic material systems for developmental cell culturing, organoid and stem cell work includes the implementation of this reciprocal nature. The largest hurdle to achieve true cell-instructive materials in biomaterials engineering is a lack of spatial and temporal control over material properties and the display of bioactive signals compared to the natural cell environment. ECM-mimicking hydrogels have been developed using a wide range of polymers, assembly and cross-linking strategies. While our synthetic toolbox is larger than nature, often our systems underperform when compared to ECM systems with natural components like Matrigel. Material properties and three-dimensional structure ill-represent the three-dimensional ECM reciprocal nature and ligand presentation is an oversimplified version of the complexity found in nature. We hypothesize that the lack of programmable control in properties and ligand presentation forms the basis of this mismatch in performance and analyze the presence of control in current state of the art ECM-mimicking systems based on covalent, supramolecular and recombinant polymers. We conclude that through combining the dynamics of supramolecular materials, robustness from covalent systems and the programmable spatial control of bio-activation in recombinant ECM materials, the optimal synthetic artificial ECM could be assembled.

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.

Orthokeratinised odontogenic cyst mimicking periapical cyst

PubMed Central

Rajalakshmi, R; Sreeja, C; Vijayalakshmi, D; Leelarani, V

2013-01-01

Orthokeratinised odontogenic cyst (OOC) denotes the odontogenic cyst that microscopically has an orthokeratinised epithelial lining. OOC is characterised by a less-aggressive behaviour and a low rate of recurrence. This report describes a case of OOC involving posterior part of the mandible that mimicked periapical cyst in a 14-year-old boy. The initial clinical diagnosis was given as periapical cyst based on the clinical and radiographical features. Enucleation of the cyst was performed and the specimen was sent for histopathological examination. A definite diagnosis of OOC was made by histopathological examination of the biopsy specimen. This case emphases on including OOC in the differential diagnosis of radiolucencies occurring in the periapical region of non-vital tooth. PMID:24099763

Orthokeratinised odontogenic cyst mimicking periapical cyst.

PubMed

Rajalakshmi, R; Sreeja, C; Vijayalakshmi, D; Leelarani, V

2013-10-07

Orthokeratinised odontogenic cyst (OOC) denotes the odontogenic cyst that microscopically has an orthokeratinised epithelial lining. OOC is characterised by a less-aggressive behaviour and a low rate of recurrence. This report describes a case of OOC involving posterior part of the mandible that mimicked periapical cyst in a 14-year-old boy. The initial clinical diagnosis was given as periapical cyst based on the clinical and radiographical features. Enucleation of the cyst was performed and the specimen was sent for histopathological examination. A definite diagnosis of OOC was made by histopathological examination of the biopsy specimen. This case emphases on including OOC in the differential diagnosis of radiolucencies occurring in the periapical region of non-vital tooth.

Antimicrobial Peptide Mimicking Primary Amine and Guanidine Containing Methacrylamide Copolymers Prepared by Raft Polymerization

PubMed Central

Exley, Sarah E.; Paslay, Lea C.; Sahukhal, Gyan S.; Abel, Brooks A.; Brown, Tyler D.; McCormick, Charles L.; Heinhorst, Sabine; Koul, Veena; Choudhary, Veena; Elasri, Mohamed O.; Morgan, Sarah E.

2016-01-01

Naturally occurring antimicrobial peptides (AMPs) display the ability to eliminate a wide variety of bacteria, without toxicity to the host eukaryotic cells. Synthetic polymers containing moieties mimicking lysine and arginine components found in AMPs have been reported to show effectiveness against specific bacteria, with the mechanism of activity purported to depend on the nature of the amino acid mimic. In an attempt to incorporate the antimicrobial activity of both amino acids into a single water-soluble copolymer, a series of copolymers containing lysine mimicking aminopropyl methacrylamide (APMA) and arginine mimicking guanadinopropyl methacrylamide (GPMA) were prepared via aqueous RAFT polymerization. Copolymers were prepared with varying ratios of the comonomers, with degree of polymerization of 35–40 and narrow molecular weight distribution to simulate naturally occurring AMPs. Antimicrobial activity was determined against Gram-negative and Gram-positive bacteria under conditions with varying salt concentration. Toxicity to mammalian cells was assessed by hemolysis of red blood cells and MTT assays of MCF-7 cells. Antimicrobial activity was observed for APMA homopolymer and copolymers with low concentrations of GPMA against all bacteria tested, with low toxicity toward mammalian cells. PMID:26558609

Development of a Tissue-Mimicking Phantom for Evaluating the Focusing Performance of High Intensity Focused Ultrasound

NASA Astrophysics Data System (ADS)

Zongyu, Jing; Faqi, Li; Jiangzhong, Zou; Zhibiao, Wang

2006-05-01

Objectives: To develop a tissue mimicking phantom which can be used to evaluate the focusing performance of the HIFU transducer, and the phantom should has the same acoustic characteristic and thermotics characteristic as the biological tissue. Materials and methods: The tissue mimicking phantom was made from water, gelatin, fresh biologic tissue Its ultrasonic parameters (attenuation coefficient) of the phantom was measured by the method of radiation pressure, and thermotics parameters of the phantom, including thermal conductivity, specific heat/fusion point et al were tested under the Measurement meter. The HIFU biological effect of the phantom was evaluated under the Model JC focused ultrasound tumor therapeutic system, developed and produced by Chongqing HIFU Technology Co. Ltd (working frequency: 0.7MHz; acoustic power: 200W; focal distance: 135mm; Acoustic focal region: 3×3×25 cubic mm). Results: The self-made phantom is sable, has smooth and glossy appearance, well-distributed construction, and good elasticity. We measured the followed values for acoustic and thermal properties: density 1049±2 kg/m3; attenuation 0.532±0.017 dB/cm (0.8 MHz), 0.612±0.021 dB/cm (1.0 MHz); thermal conductivity 0.76±0.08 W/m/-°C; specific heat 3653±143 J/kg-°C; fusion point154±8°C. The BFR induced in the phantom after HIFU exposure was stable in its size and appearance. Conclusion: We produced and improved one tissue mimicking phantom successfully which had semblable ultrasound and thermphysical properties like the soft tissue, and can replace the bovine liver to investigate the HIFU biological effect and to detect the focusing performance of the HIFU energy transducer. The research was supported by Chongqing University of Medical Science (CX200320).

Cartilage Delamination Flap Mimicking a Torn Medial Meniscus

PubMed Central

Bin Abd Razak, Hamid Rahmatullah; Amit Kanta, Mitra

2016-01-01

We report a case of a chondral delamination lesion due to medial parapatellar plica friction syndrome involving the medial femoral condyle. This mimicked a torn medial meniscus in clinical and radiological presentation. Arthroscopy revealed a chondral delamination flap, which was debrided. Diagnosis of chondral lesions in the knee can be challenging. Clinical examination and MRI have good accuracy for diagnosis and should be used in tandem. Early diagnosis and treatment of chondral lesions are important to prevent progression to early osteoarthritis. PMID:28070434

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.

Floating retained root lesion mimicking apical periodontitis.

PubMed

Chung, Ming-Pang; Chen, Chih-Ping; Shieh, Yi-Shing

2009-10-01

A case of a retained root tip simulating apical periodontitis on radiographic examination is described. The retained root tip, originating from the left lower first molar, floated under the left lower second premolar apical region mimicking apical periodontitis. It appeared as an ill-defined periapical radiolucency containing a smaller radiodense mass on radiograph. The differential diagnosis included focal sclerosing osteomyelitis (condensing osteitis) and ossifying fibroma. Upon exicisional biopsy, a retained root associated with granulation tissue was found. After 1-year follow-up, the patient was asymptomatic and the periradicular lesion was healing. Meanwhile, the associated tooth showed a normal response to stimulation testing.

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.

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

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.

Addison's Disease Mimicking as Acute Pancreatitis: A Case Report.

PubMed

Chaudhuri, Sayani; Rao, Karthik N; Patil, Navin; Ommurugan, Balaji; Varghese, George

2017-04-01

Over past two decades there has been significant improvement in medical field in elucidating the underlying pathophysiology and genetics of Addison's disease. Adrenal insufficiency (Addison's disease) is a rare disease with an incidence of 0.8/100,000 cases. The diagnosis may be delayed if the clinical presentation mimics a gastrointestinal disorder or psychiatric illness. We report a case of Addison's disease presenting as acute pain in abdomen mimicking clinical presentation of acute pancreatitis.

Inhibition of Human Metapneumovirus Binding to Heparan Sulfate Blocks Infection in Human Lung Cells and Airway Tissues

PubMed Central

Klimyte, Edita M.; Smith, Stacy E.; Oreste, Pasqua; Lembo, David

2016-01-01

ABSTRACT Human metapneumovirus (HMPV), a recently discovered paramyxovirus, infects nearly 100% of the world population and causes severe respiratory disease in infants, the elderly, and immunocompromised patients. We previously showed that HMPV binds heparan sulfate proteoglycans (HSPGs) and that HMPV binding requires only the viral fusion (F) protein. To characterize the features of this interaction critical for HMPV binding and the role of this interaction in infection in relevant models, we utilized sulfated polysaccharides, heparan sulfate mimetics, and occluding compounds. Iota-carrageenan demonstrated potent anti-HMPV activity by inhibiting binding to lung cells mediated by the F protein. Furthermore, analysis of a minilibrary of variably sulfated derivatives of Escherichia coli K5 polysaccharide mimicking the HS structure revealed that the highly O-sulfated K5 polysaccharides inhibited HMPV infection, identifying a potential feature of HS critical for HMPV binding. The peptide dendrimer SB105-A10, which binds HS, reduced binding and infection in an F-dependent manner, suggesting that occlusion of HS at the target cell surface is sufficient to prevent infection. HMPV infection was also inhibited by these compounds during apical infection of polarized airway tissues, suggesting that these interactions take place during HMPV infection in a physiologically relevant model. These results reveal key features of the interaction between HMPV and HS, supporting the hypothesis that apical HS in the airway serves as a binding factor during infection, and HS modulating compounds may serve as a platform for potential antiviral development. IMPORTANCE Human metapneumovirus (HMPV) is a paramyxovirus that causes respiratory disease worldwide. It has been previously shown that HMPV requires binding to heparan sulfate on the surfaces of target cells for attachment and infection. In this study, we characterize the key features of this binding interaction using heparan sulfate

Mycobacterium tuberculosis infection within parotid gland Warthin tumor.

PubMed

Ozcan, Cengiz; Apa, Duygu Düşmez; Aslan, Gönül; Gülhan, Stk; Görür, Kemal

2008-11-01

Tuberculosis of the parotid gland is extremely unusual. Tuberculosis comprises 2.5% to 10% of parotid gland lesions. Two clinical forms of parotid gland tuberculosis infection exist. One is a diffuse parenchymatous disease (either primary or secondary to nodal disease), resembling common infection. The second is a chronic, slow-growing, painless, and firm parotid mass mimicking a neoplasm. Most of these patients were diagnosed after parotid gland surgery and histopathologic evaluation. Warthin tumor is a well-known benign neoplasm of the salivary glands. It is the second most common tumor of the parotid gland. Mycobacterium tuberculosis within Warthin tumor is also unusual. Five cases with parotid gland tuberculosis within Warthin tumor were reported in the literature. In this report, we present a new patient with parotid gland tuberculosis within the Warthin tumor. This type parotid gland pathology is an extremely rare entity, and to the best of our knowledge, this is the second documented case using polymerase chain reaction. We also discussed the possible mechanisms of development of infection within Warthin tumor.

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.

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.

Characterization of a hyper-viscoelastic phantom mimicking biological soft tissue using an abdominal pneumatic driver with Magnetic Resonance Elastography (MRE)

PubMed Central

Leclerc, Gwladys E.; Debernard, Laetitia; Foucart, Félix; Robert, Ludovic; Pelletier, Kay M.; Charleux, Fabrice; Ehman, Richard; Tho, Marie-Christine Ho Ba; Bensamoun, Sabine F.

2012-01-01

The purpose of this study was to create a polymer phantom mimicking the mechanical properties of soft tissues using experimental tests and rheological models. Multifrequency Magnetic Resonance Elastography (MMRE) tests were performed on the present phantom with a pneumatic driver to characterize the viscoelastic (μ, η) properties using Voigt, Maxwell, Zener and Springpot models. To optimize the MMRE protocol, the driver behavior was analyzed with a vibrometer. Moreover, the hyperelastic properties of the phantom were determined using compressive tests and Mooney-Rivlin model. The range of frequency to be used with the round driver was found between 60 Hz and 100 Hz as it exhibits one type of vibration mode for the membrane. MRE analysis revealed an increase in the shear modulus with frequency reflecting the viscoelastic properties of the phantom showing similar characteristic of soft tissues. Rheological results demonstrated that Springpot model better revealed the viscoelastic properties (μ = 3.45 kPa, η = 6.17 Pa.s) of the phantom and the Mooney-Rivlin coefficients were C10 = 1.09.10-2 MPa and C01 = −8.96.10-3 MPa corresponding to μ = 3.95 kPa. These studies suggest that the phantom, mimicking soft tissue, could be used for preliminary MRE tests to identify the optimal parameters necessary for in vivo investigations. Further developments of the phantom may allow clinicians to more accurately mimic healthy and pathological soft tissues using MRE. PMID:22284992

Characterization of a hyper-viscoelastic phantom mimicking biological soft tissue using an abdominal pneumatic driver with magnetic resonance elastography (MRE).

PubMed

Leclerc, Gwladys E; Debernard, Laëtitia; Foucart, Félix; Robert, Ludovic; Pelletier, Kay M; Charleux, Fabrice; Ehman, Richard; Ho Ba Tho, Marie-Christine; Bensamoun, Sabine F

2012-04-05

The purpose of this study was to create a polymer phantom mimicking the mechanical properties of soft tissues using experimental tests and rheological models. Multifrequency Magnetic Resonance Elastography (MMRE) tests were performed on the present phantom with a pneumatic driver to characterize the viscoelastic (μ, η) properties using Voigt, Maxwell, Zener and Springpot models. To optimize the MMRE protocol, the driver behavior was analyzed with a vibrometer. Moreover, the hyperelastic properties of the phantom were determined using compressive tests and Mooney-Rivlin model. The range of frequency to be used with the round driver was found between 60 Hz and 100 Hz as it exhibits one type of vibration mode for the membrane. MRE analysis revealed an increase in the shear modulus with frequency reflecting the viscoelastic properties of the phantom showing similar characteristic of soft tissues. Rheological results demonstrated that Springpot model better revealed the viscoelastic properties (μ=3.45 kPa, η=6.17 Pas) of the phantom and the Mooney-Rivlin coefficients were C(10)=1.09.10(-2) MPa and C(01)=-8.96.10(-3) MPa corresponding to μ=3.95 kPa. These studies suggest that the phantom, mimicking soft tissue, could be used for preliminary MRE tests to identify the optimal parameters necessary for in vivo investigations. Further developments of the phantom may allow clinicians to more accurately mimic healthy and pathological soft tissues using MRE. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

Heme Catabolism by Heme Oxygenase-1 Confers Host Resistance to Mycobacterium Infection

PubMed Central

Silva-Gomes, Sandro; Appelberg, Rui; Larsen, Rasmus; Soares, Miguel Parreira

2013-01-01

Heme oxygenases (HO) catalyze the rate-limiting step of heme degradation. The cytoprotective action of the inducible HO-1 isoform, encoded by the Hmox1 gene, is required for host protection against systemic infections. Here we report that upregulation of HO-1 expression in macrophages (Mϕ) is strictly required for protection against mycobacterial infection in mice. HO-1-deficient (Hmox1−/−) mice are more susceptible to intravenous Mycobacterium avium infection, failing to mount a protective granulomatous response and developing higher pathogen loads, than infected wild-type (Hmox1+/+) controls. Furthermore, Hmox1−/− mice also develop higher pathogen loads and ultimately succumb when challenged with a low-dose aerosol infection with Mycobacterium tuberculosis. The protective effect of HO-1 acts independently of adaptive immunity, as revealed in M. avium-infected Hmox1−/− versus Hmox1+/+ SCID mice lacking mature B and T cells. In the absence of HO-1, heme accumulation acts as a cytotoxic pro-oxidant in infected Mϕ, an effect mimicked by exogenous heme administration to M. avium-infected wild-type Mϕ in vitro or to mice in vivo. In conclusion, HO-1 prevents the cytotoxic effect of heme in Mϕ, contributing critically to host resistance to Mycobacterium infection. PMID:23630967

Effects of the synthetic corticosteroid dexamethasone on bovine herpesvirus 1 productive infection.

PubMed

Zhu, Liqian; Thompson, Jesse; Ma, Fangrui; Eudy, James; Jones, Clinton

2017-05-01

Sensory neurons are a primary site for life-long latency of bovine herpesvirus 1 (BoHV-1). The synthetic corticosteroid dexamethasone induces reactivation from latency and productive infection, in part because the BoHV-1 genome contains more than 100 glucocorticoid receptor (GR) responsive elements (GREs). Two GREs in the immediate early transcription unit 1 promoter are required for dexamethasone induction. Recent studies also demonstrated that the serum and glucocorticoid receptor protein kinase (SGK) family stimulated BoHV-1 replication. Consequently, we hypothesized that dexamethasone influences several aspects of productive infection. In this study, we demonstrated that dexamethasone increased expression of the immediate early protein bICP4, certain late transcripts, and UL23 (thymidine kinase) by four hours after infection. SGK1 expression and Akt phosphorylation were also stimulated during early stages of infection and dexamethasone treatment further increased this effect. These studies suggest that stress, as mimicked by dexamethasone treatment, has the potential to stimulate productive infection by multiple pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

Structure-Based Design of Inhibitors of Protein–Protein Interactions: Mimicking Peptide Binding Epitopes

PubMed Central

Pelay-Gimeno, Marta; Glas, Adrian; Koch, Oliver; Grossmann, Tom N

2015-01-01

Protein–protein interactions (PPIs) are involved at all levels of cellular organization, thus making the development of PPI inhibitors extremely valuable. The identification of selective inhibitors is challenging because of the shallow and extended nature of PPI interfaces. Inhibitors can be obtained by mimicking peptide binding epitopes in their bioactive conformation. For this purpose, several strategies have been evolved to enable a projection of side chain functionalities in analogy to peptide secondary structures, thereby yielding molecules that are generally referred to as peptidomimetics. Herein, we introduce a new classification of peptidomimetics (classes A–D) that enables a clear assignment of available approaches. Based on this classification, the Review summarizes strategies that have been applied for the structure-based design of PPI inhibitors through stabilizing or mimicking turns, β-sheets, and helices. PMID:26119925

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.

Spontaneous motor entrainment to music in multiple vocal mimicking species.

PubMed

Schachner, Adena; Brady, Timothy F; Pepperberg, Irene M; Hauser, Marc D

2009-05-26

The human capacity for music consists of certain core phenomena, including the tendency to entrain, or align movement, to an external auditory pulse [1-3]. This ability, fundamental both for music production and for coordinated dance, has been repeatedly highlighted as uniquely human [4-11]. However, it has recently been hypothesized that entrainment evolved as a by-product of vocal mimicry, generating the strong prediction that only vocal mimicking animals may be able to entrain [12, 13]. Here we provide comparative data demonstrating the existence of two proficient vocal mimicking nonhuman animals (parrots) that entrain to music, spontaneously producing synchronized movements resembling human dance. We also provide an extensive comparative data set from a global video database systematically analyzed for evidence of entrainment in hundreds of species both capable and incapable of vocal mimicry. Despite the higher representation of vocal nonmimics in the database and comparable exposure of mimics and nonmimics to humans and music, only vocal mimics showed evidence of entrainment. We conclude that entrainment is not unique to humans and that the distribution of entrainment across species supports the hypothesis that entrainment evolved as a by-product of selection for vocal mimicry.

Atmospheric modeling of Mars CH4 subsurface clathrates releases mimicking SAM and 2003 Earth-based detections

NASA Astrophysics Data System (ADS)

Pla-Garcia, Jorge

2017-10-01

The aim of this work is to establish the amount of mixing during all martian seasons to test whether CH4 releases inside or outside of Gale crater are consistent with MSL-SAM observations. Several modeling scenarios were configured, including instantaneous and steady releases, both inside and outside the crater. A simulation to mimic the 2003 Earth-based detections (Mumma et al. 2009 or M09) was also performed. In the instantaneous release inside Gale experiments, Ls270 was shown to be the faster mixing season when air within and outside the crater was well mixed: all tracer mass inside the crater is diluted after just 8 hours. The mixing of near surface crater air with the external environment in the rest of the year is potentially rapid but slower than Ls270. In the instantaneous release outside Gale (NW) experiment, in just 12 hours the CH4 that makes it to the MSL landing location is diluted by six orders of magnitude. The timescale of mixing in the model is on the order of 1 sol regardless of season. The duration of the CH4 peak observed by SAM is 100 sols. Therefore there is a steady release inside the crater, or there is a large magnitude steady release outside the crater. In the steady release Gale experiments, CH4 flux rate from ground is 1.8 kg m-2 s-1 (Gloesener et al. 2017) and it is not predictive. In these experiments, ~200 times lower CH4 values detected by SAM are modeled around MSL location. There are CH4 concentration variations of orders of magnitude depending on the hour, so timing of SAM measurements is important. With a larger (but further away) outside crater release area compared to inside, similar CH4 values around MSL are modeled, so distance to source is important. In the steady experiments mimicking M09 detection release area, only 12 times lower CH4 values detected by SAM are modeled around MSL. The highest value in the M09 modeled scenario (0.6 ppbv) is reached in Ls270. This value is the highest of all modeled experiments. With our

Reversible wavefront shaping between Gaussian and Airy beams by mimicking gravitational field

NASA Astrophysics Data System (ADS)

Wang, Xiangyang; Liu, Hui; Sheng, Chong; Zhu, Shining

2018-02-01

In this paper, we experimentally demonstrate reversible wavefront shaping through mimicking gravitational field. A gradient-index micro-structured optical waveguide with special refractive index profile was constructed whose effective index satisfying a gravitational field profile. Inside the waveguide, an incident broad Gaussian beam is firstly transformed into an accelerating beam, and the generated accelerating beam is gradually changed back to a Gaussian beam afterwards. To validate our experiment, we performed full-wave continuum simulations that agree with the experimental results. Furthermore, a theoretical model was established to describe the evolution of the laser beam based on Landau’s method, showing that the accelerating beam behaves like the Airy beam in the small range in which the linear potential approaches zero. To our knowledge, such a reversible wavefront shaping technique has not been reported before.

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.

Ileal Entrapment within a Paracaecal Hernia Mimicking Acute Appendicitis

PubMed Central

Birchley, David

2009-01-01

Presented is a case of incarcerated paracaecal hernia mimicking acute appendicitis. The clinical scenario highlights the need for a high index of suspicion in the management of patients with localised peritonism even in the absence of obstructive symptoms and the presence of normal laboratory markers of inflammation.Whilst computed tomography might offer a pre-operative diagnosis, in such a low-risk patient laparoscopy offers the combined advantages of immediate diagnosis and definitive treatment of acute pathology. PMID:19317924

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

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

Protein-mimicking nanowire-inspired electro-catalytic biosensor for probing acetylcholinesterase activity and its inhibitors.

PubMed

Zhang, Qingqing; Hu, Yufang; Wu, Di; Ma, Shaohua; Wang, Jiao; Rao, Jiajia; Xu, Lihua; Xu, Huan; Shao, Huili; Guo, Zhiyong; Wang, Sui

2018-06-01

A highly sensitive electrochemical biosensor based on the synthetized L-Cysteine-Ag(I) coordination polymer (L-Cys-Ag(I) CP), which looks like a protein-mimicking nanowire, was constructed to detect acetylcholinesterase (AChE) activity and screen its inhibitors. This sensing strategy involves the reaction of acetylcholine chloride (ACh) with acetylcholinesterase (AChE) to form choline that is in turn catalytically oxidized by choline oxidase (ChOx) to produce hydrogen peroxide (H 2 O 2 ), thus L-Cys-Ag(I) CP possesses the electro-catalytic property to H 2 O 2 reduction. Herein, the protein-mimicking nanowire-based platform was capable of investigating successive of H 2 O 2 effectively by amperometric i-t (current-time) response, and was further applied for the turn-on electrochemical detection of AChE activity. The proposed sensor is highly sensitive (limit of detection is 0.0006 U/L) and is feasible for screening inhibitors of AChE. The model for AChE inhibition was further established and two traditional AChE inhibitors (donepezil and tacrine) were employed to verify the feasibility of the system. The IC 5 0 of donepezil and tacrine were estimated to be 1.4 nM and 3.5 nM, respectively. The developed protocol provides a new and promising platform for probing AChE activity and screening its inhibitors with low cost, high sensitivity and selectivity. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

Mimicking the action of folding chaperones by Hamiltonian replica-exchange molecular dynamics simulations: application in the refinement of de novo models.

PubMed

Fan, Hao; Periole, Xavier; Mark, Alan E

2012-07-01

The efficiency of using a variant of Hamiltonian replica-exchange molecular dynamics (Chaperone H-replica-exchange molecular dynamics [CH-REMD]) for the refinement of protein structural models generated de novo is investigated. In CH-REMD, the interaction between the protein and its environment, specifically, the electrostatic interaction between the protein and the solvating water, is varied leading to cycles of partial unfolding and refolding mimicking some aspects of folding chaperones. In 10 of the 15 cases examined, the CH-REMD approach sampled structures in which the root-mean-square deviation (RMSD) of secondary structure elements (SSE-RMSD) with respect to the experimental structure was more than 1.0 Å lower than the initial de novo model. In 14 of the 15 cases, the improvement was more than 0.5 Å. The ability of three different statistical potentials to identify near-native conformations was also examined. Little correlation between the SSE-RMSD of the sampled structures with respect to the experimental structure and any of the scoring functions tested was found. The most effective scoring function tested was the DFIRE potential. Using the DFIRE potential, the SSE-RMSD of the best scoring structures was on average 0.3 Å lower than the initial model. Overall the work demonstrates that targeted enhanced-sampling techniques such as CH-REMD can lead to the systematic refinement of protein structural models generated de novo but that improved potentials for the identification of near-native structures are still needed. Copyright © 2012 Wiley Periodicals, Inc.

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.

Borrelia Lymphocytoma Mimicking Butterfly Rash in a Pediatric Patient.

PubMed

Llamas-Velasco, Mar; Paredes, Bruno Emilio

2018-03-01

A 5-year-old girl presented with a facial butterfly rash that persisted for 5 months without arthralgia, fever, malaise, photosensitivity, or other symptoms. Lupus erythematosus was clinically suspected. All blood tests were negative or within normal values. Skin biopsy showed a dense nodular superficial and deep inflammatory infiltrate of lymphocytes that reaches subcutaneous tissue. The most striking histopathological finding was plasma cells with some perifollicular accentuation. Borrelia polymerase chain reaction assay of the tissue was positive, and we made the diagnoses of borrelia lymphocytoma mimicking butterfly rash of lupus erythematosus. The lesions disappeared with amoxicillin followed by cefuroxime for 28 days. In children, a variety of diseases including lupus erythematous may lead to a butterfly rash that is usually short lasting and commonly associated with systemic symptoms. Borreliosis may be related with long-lasting facial erythema in children and may mimic lupus and present high titers of antinuclear antibodies. In any case, borrelial lymphocytoma has not been previously reported as a cause of butterfly rash, thus mimicking acute lupus in a child, as in our case. From a histopathological point of view, the presence of plasma cells in a pseudolymphomatous infiltrate is a clue for the right diagnosis. Therefore, we suggest that borrelia serology should be done in children with butterfly rash lasting more than a month and empirical antibiotic treatment should be tried even in cases with negative serology.

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

Subaortic membrane mimicking hypertrophic cardiomyopathy.

PubMed

Anderson, Mark Joseph; Arruda-Olson, Adelaide; Gersh, Bernard; Geske, Jeffrey

2015-11-04

A 34-year-old man was referred for progressive angina and exertional dyspnoea refractory to medical therapy, with a presumptive diagnosis of hypertrophic cardiomyopathy (HCM). Transthoracic echocardiography (TTE) revealed asymmetric septal hypertrophy without systolic anterior motion of the mitral valve leaflet and with no dynamic left ventricular outflow tract (LVOT) obstruction. However, the LVOT velocity was elevated at rest as well as with provocation, without the characteristic late peaking obstruction seen in HCM. Focused TTE to evaluate for suspected fixed obstruction demonstrated a subaortic membrane 2.2 cm below the aortic valve. Coronary CT angiography confirmed the presence of the subaortic membrane and was negative for concomitant coronary artery disease. Surgical resection of the subaortic membrane and septal myectomy resulted in significant symptomatic relief and lower LVOT velocities on postoperative TTE. This case reminds the clinician to carefully evaluate for alternative causes of LVOT obstruction, especially subaortic membrane, as a cause of symptoms mimicking HCM. 2015 BMJ Publishing Group Ltd.

Subaortic membrane mimicking hypertrophic cardiomyopathy

PubMed Central

Anderson, Mark Joseph; Arruda-Olson, Adelaide; Gersh, Bernard; Geske, Jeffrey

2015-01-01

A 34-year-old man was referred for progressive angina and exertional dyspnoea refractory to medical therapy, with a presumptive diagnosis of hypertrophic cardiomyopathy (HCM). Transthoracic echocardiography (TTE) revealed asymmetric septal hypertrophy without systolic anterior motion of the mitral valve leaflet and with no dynamic left ventricular outflow tract (LVOT) obstruction. However, the LVOT velocity was elevated at rest as well as with provocation, without the characteristic late peaking obstruction seen in HCM. Focused TTE to evaluate for suspected fixed obstruction demonstrated a subaortic membrane 2.2 cm below the aortic valve. Coronary CT angiography confirmed the presence of the subaortic membrane and was negative for concomitant coronary artery disease. Surgical resection of the subaortic membrane and septal myectomy resulted in significant symptomatic relief and lower LVOT velocities on postoperative TTE. This case reminds the clinician to carefully evaluate for alternative causes of LVOT obstruction, especially subaortic membrane, as a cause of symptoms mimicking HCM. PMID:26538250

Humanlike Robots - Synthetically Mimicking Humans

NASA Technical Reports Server (NTRS)

Bar-Cohen, Yoseph

2012-01-01

Nature inspired many inventions and the field of technology that is based on the mimicking or inspiration of nature is widely known as Biomimetics and it is increasingly leading to many new capabilities. There are numerous examples of biomimetic successes including the copying of fins for swimming, and the inspiration of the insects and birds flight. More and more commercial implementations of biomimetics are appearing and behaving lifelike and applications are emerging that are important to our daily life. Making humanlike robots is the ultimate challenge to biomimetics and, for many years, it was considered science fiction, but such robots are becoming an engineering reality. Advances in producing such robot are allowing them to perform impressive functions and tasks. The development of such robots involves addressing many challenges and is raising concerns that are related to fear of their application implications and potential ethical issues. In this paper, the state-of-the-art of humanlike robots, potential applications and challenges will be reviewed.

A rare case of primary bone lymphoma mimicking a pelvic abscess

PubMed Central

Al Wattar, BH; Mohanty, K

2011-01-01

Primary bone lymphoma (PBL) is a rare, malignant, neoplastic disorder of the skeleton that accounts for less than 5% of all primary bone tumours. We present an extremely rare case of PBL mimicking a pelvic abscess around the sacroiliac joint, which has never been reported in the medical literature, and discuss learning points highlighted from this case. PMID:22004625

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

Berberine Improves Intestinal Motility and Visceral Pain in the Mouse Models Mimicking Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D) Symptoms in an Opioid-Receptor Dependent Manner

PubMed Central

Pan, Qiuhui; Fichna, Jakub; Zheng, Lijun; Wang, Kesheng; Yu, Zhen; Li, Yongyu; Li, Kun; Song, Aihong; Liu, Zhongchen; Song, Zhenshun; Kreis, Martin

2015-01-01

Background and Aims Berberine and its derivatives display potent analgesic, anti-inflammatory and anticancer activity. Here we aimed at characterizing the mechanism of action of berberine in the gastrointestinal (GI) tract and cortical neurons using animal models and in vitro tests. Methods The effect of berberine was characterized in murine models mimicking diarrhea-predominant irritable bowel syndrome (IBS-D) symptoms. Then the opioidantagonists were used to identify the receptors involved. Furthermore, the effect of berberineon opioid receptors expression was established in the mouse intestine and rat fetal cortical neurons. Results In mouse models, berberine prolonged GI transit and time to diarrhea in a dose-dependent manner, and significantly reduced visceral pain. In physiological conditions the effects of berberine were mediated by mu- (MOR) and delta- (DOR) opioidreceptors; hypermotility, excessive secretion and nociception were reversed by berberine through MOR and DOR-dependent action. We also found that berberine increased the expression of MOR and DOR in the mouse bowel and rat fetal cortical neurons. Conclusion Berberine significantly improved IBS-D symptoms in animal models, possibly through mu- and delta- opioid receptors. Berberine may become a new drug candidate for the successful treatment of IBS-D in clinical conditions. PMID:26700862

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

Atmospheric modeling of Mars CH4 subsurface clathrates releases mimicking SAM and 2003 Earth-based detections

NASA Astrophysics Data System (ADS)

Pla-García, J.; Rafkin, S. C.

2017-12-01

The aim of this work is to establish the amount of mixing during all martian seasons to test whether CH4 releases inside or outside of Gale crater are consistent with MSL-SAM observations. Several modeling scenarios were configured, including instantaneous and steady releases, both inside and outside the crater. A simulation to mimic the 2003 Earth-based detections (Mumma et al. 2009 or M09) was also performed. In the instantaneous release inside Gale experiments, Ls270 was shown to be the faster mixing season when air within and outside the crater was well mixed: all tracer mass inside the crater is diluted after just 8 hours. The mixing of near surface crater air with the external environment in the rest of the year is potentially rapid but slower than Ls270.In the instantaneous release outside Gale (NW) experiment, in just 12 hours the CH4 that makes it to the MSL landing location is diluted by six orders of magnitude. The timescale of mixing in MRAMS experiments is on the order of 1 sol regardless of season. The duration of the CH4 peak observed by SAM is 100 sols. Therefore there is a steady release inside the crater, or there is a very large magnitude steady release outside the crater. In the steady release Gale experiments, CH4 flux rate from ground is 1.8 kg m-2 s-1 (derived from Gloesener et al. 2017 clathrates fluxes) and it is not predictive. In these experiments, 200 times lower CH4 values detected by SAM are modeled around MSL location. There are CH4 concentration variations of orders of magnitude depending on the hour, so timing of SAM measurements is important. With a larger (but further away) outside crater release area compared to inside, similar CH4 values around MSL are modeled, so distance to source is important. In the steady experiments mimicking M09 detection release area, only 12 times lower CH4 values detected by SAM are modeled around MSL. The highest value in the M09 modeled scenario (0.6 ppbv) is reached in Ls270. This value is the

[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.

Investigation of Tumor Cell Behaviors on a Vascular Microenvironment-Mimicking Microfluidic Chip

PubMed Central

Huang, Rong; Zheng, Wenfu; Liu, Wenwen; Zhang, Wei; Long, Yunze; Jiang, Xingyu

2015-01-01

The extravasation of tumor cells is a key event in tumor metastasis. However, the mechanism underlying tumor cell extravasation remains unknown, mainly hindered by obstacles from the lack of complexity of biological tissues in conventional cell culture, and the costliness and ethical issues of in vivo experiments. Thus, a cheap, time and labor saving, and most of all, vascular microenvironment-mimicking research model is desirable. Herein, we report a microfluidic chip-based tumor extravasation research model which is capable of simultaneously simulating both mechanical and biochemical microenvironments of human vascular systems and analyzing their synergistic effects on the tumor extravasation. Under different mechanical conditions of the vascular system, the tumor cells (HeLa cells) had the highest viability and adhesion activity in the microenvironment of the capillary. The integrity of endothelial cells (ECs) monolayer was destroyed by tumor necrosis factor-α (TNF-α) in a hemodynamic background, which facilitated the tumor cell adhesion, this situation was recovered by the administration of platinum nanoparticles (Pt-NPs). This model bridges the gap between cell culture and animal experiments and is a promising platform for studying tumor behaviors in the vascular system. PMID:26631692

Fibroadenoma in Axillary Ectopic Breast Tissue Mimicking Lymphadenopathy

PubMed Central

Maheshwari, Ujwala M

2017-01-01

Swellings in the axilla especially in women are always viewed with suspicion owing to a large number of these being associated with breast carcinoma presenting as nodal metastasis. In a country like India, tuberculous lymphadenopathy is also amongst the first differentials. We present a case of a woman with right sided axillary swelling mimicking lymphadenopathy which on Fine Needle Aspiration Cytology (FNAC) turned out to be fibroadenoma of the ectopic breast tissue. This condition is a rare occurrence in Ectopic Breast Tissue (EBT) as opposed to that in the normal breast, the most common pathology affecting ectopic breast being carcinomas. PMID:28511397

Simple bone cyst of mandible mimicking periapical cyst.

PubMed

Hs, Charan Babu; Rai, Bhagawan Das; Nair, Manju A; Astekar, Madhusudan S

2012-05-29

Simple bone cysts (SBC) are pseudocysts occurring less commonly in the maxillofacial region. The uncertain and unclear etiopathogenesis led to numerous synonyms to refer this particular cyst. These cysts are devoid of an epithelial lining and are usually empty or contain blood or straw-colored fluid. In jaws initially it mimics a periapical cyst and later can lead to cortical bone expansion warranting for radical approach, which is seldom required. SBC is predominantly diagnosed in first two decades of life. Here we report a case of solitary bone cyst mimicking a periapical cyst of a mandibular molar in a 37-year-old patient.

Tinea capitis caused by Trichophyton rubrum mimicking favus.

PubMed

Boyd, Alan S

2016-12-01

Favus is an uncommon form of tinea capitis (TC) currently seen in geographic areas with poor sanitation and limited access to health care such as emerging nations. Several variants of this condition have been described including one exhibiting a plaque composed of parchmentlike material. The makeup of this plaque has not been described. Tinea capitis is rare in adults, particularly when the infectious agent is Trichophyton rubrum , and affected patients often exhibit comorbidities associated with diminished immune surveillance. This case report describes an elderly woman with TC due to T rubrum mimicking a rare form of favus.

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

Herpes zoster sciatica mimicking lumbar canal stenosis: a case report.

PubMed

Koda, Masao; Mannoji, Chikato; Oikawa, Makiko; Murakami, Masazumi; Okamoto, Yuzuru; Kon, Tamiyo; Okawa, Akihiko; Ikeda, Osamu; Yamazaki, Masashi; Furuya, Takeo

2015-07-29

Symptom of herpes zoster is sometimes difficult to distinguish from sciatica induced by spinal diseases, including lumbar disc herniation and spinal canal stenosis. Here we report a case of sciatica mimicking lumbar canal stenosis. A 74-year-old Chinese male patient visited our hospital for left-sided sciatic pain upon standing or walking for 5 min of approximately 1 month's duration. At the first visit to our hospital, there were no skin lesions. A magnetic resonance imaging showed spinal canal stenosis between the 4th and 5th lumbar spine. Thus, we diagnosed the patient with sciatica induced by spinal canal stenosis. We considered decompression surgery for the stenosis of 4th and 5th lumbar spine because conservative therapy failed to relieve the patient's symptom. At that time, the patient complained of a skin rash involving his left foot for several days. A vesicular rash and erythema were observed on the dorsal and plantar surfaces of the great toe and lateral malleolus. The patient was diagnosed with herpes zoster in the left 5th lumbar spinal nerve area based on clinical findings, including the characteristics of the pain and vesicular rash and erythema in the 5th lumbar spinal dermatome. The patient was treated with famciclovir (1,500 mg/day) and non-steroidal anti-inflammatory drugs. After 1 week of medication, the skin rash resolved and pain relief was obtained. In conclusion, spinal surgeons should keep in mind herpes zoster infection as one of the possible differential diagnoses of sciatica, even if there is no typical skin rash.

Fate of pathogenic bacteria in microcosms mimicking human body sites.

PubMed

Castellani, Francesco; Ghidini, Valentina; Tafi, Maria Carla; Boaretti, Marzia; Lleo, Maria M

2013-07-01

During the infectious process, pathogens may reach anatomical sites where they are exposed to substances interfering with their growth. These substances can include molecules produced by the host, and his resident microbial population, as well as exogenous antibacterial drugs. Suboptimal concentrations of inhibitory molecules and stress conditions found in vivo (high or low temperatures, lack of oxygen, extreme pH) might induce in bacteria the activation of survival mechanisms blocking their division capability but allowing them to stay alive. These "dormant" bacteria can be reactivated in particular circumstances and would be able to express their virulence traits. In this study, it was evaluated the effect of some environmental conditions, such as optimal and suboptimal temperatures, direct light and antibiotic sub-inhibitory concentrations doses of antibiotic, on the human pathogens Escherichia coli and Enterococcus faecalis when incubated in fluids accumulated in the body of patients with different pathologies. It is shown that inoculation in a number of accumulated body fluids and the presence of gentamicin, reliable conditions encountered during pathological states, induce stress-responding strategies enabling bacteria to persist in microcosms mimicking the human body. Significant differences were detected in Gram-negative and Gram-positive species with E. faecalis surviving, as starved or viable but non-culturable forms, in any microcosm and condition tested and E. coli activating a viable but non-culturable state only in some clinical samples. The persistence of bacteria under these conditions, being non-culturable, might explain some recurrent infections without isolation of the causative agent after application of the standard microbiological methods.

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.

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.

P-HPB-21: Isolated pancreatic tuberculosis mimicking inoperable pancreatic cancer

PubMed Central

Sahu, Manoj Kumar; Singh, Ayashkanta; Behera, Debasmita; Behera, Manas; Narayan, Jimmy

2017-01-01

Background: Pancreatic tuberculosis is an uncommon disease, presenting as hypoechoic mass on imaging mimicking malignancy. Consequently, it represents a diagnostic challenge necessitating a tissue diagnosis. Case Report: A 75-year-old female presented with progressive jaundice and weight loss; imaging with computed tomography (CT) showed a large (5.8 cm × 4.6 cm) pancreatic head mass with encasement of portal and superior mesenteric veins, peripancreatic nodes, atrophic pancreatic parenchyma, and dilated main pancreatic duct. Cancer antigen 19-9 was moderately elevated. With a diagnosis of inoperable pancreatic malignancy, she was planned for tissue diagnosis and palliative chemotherapy. Endoscopic ultrasonography (EUS) showed a heterogeneous mass with vascular invasion as in the CT. Fine needle aspiration (FNA) and biliary decompression with a plastic stent performed in the same sitting. Cytology demonstrated granuloma with caseous necrosis and presence of acid-fast bacilli. Antituberculosis treatment was started, and repeat CT after 6 months showed resolution of the mass. Discussion and Conclusion: A diagnosis of isolated pancreatic tuberculosis is rare and is difficult by clinical presentation alone; in India, it should be considered as a differential diagnosis of a pancreatic tumor. Benign lesions can also present with vascular invasions mimicking inoperable malignancy. EUS FNA is a very useful tool in accurate diagnosis of pancreatic head mass avoiding unnecessary surgeries.

An Unusual Foreign Body in the Urinary Bladder Mimicking a Parasitic Worm

PubMed Central

Schmitt, Bryan H.; Feder, Marc T.; Rokke, Denise L.; Moyer, Thomas P.

2012-01-01

We report an unusual case of a foreign body removed from the urinary bladder of a 63-year-old male which mimicked a parasitic worm. The foreign body was identified as an artificial fishing worm by morphological comparison to a similar commercially produced product and by infrared spectrum analysis. PMID:22535991

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.

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.

Thalamic Amnesia Mimicking Transient Global Amnesia.

PubMed

Giannantoni, Nadia M; Lacidogna, Giordano; Broccolini, Aldobrando; Pilato, Fabio; Profice, Paolo; Morosetti, Roberta; Caliandro, Pietro; Gambassi, Giovanni; Della Marca, Giacomo; Frisullo, Giovanni

2015-06-01

Transient global amnesia is a benign syndrome and one of the most frequent discharges from the emergency department that can hardly be distinguished from other mimicking diseases. No consensus in the evaluation of transient global amnesia has yet been found in the emergency setting. We describe a 69-year-old woman who presented to our emergency department with an abrupt onset of anterograde amnesia, preceded by a similar amnesic episode misinterpreted as transient global amnesia. Neuroradiologic, neuropsychological, and neurophysiological evaluations supported the diagnosis of vascular thalamic amnesia. We report a patient who clinically fulfilled transient global amnesia's criteria and in whom nevertheless was disclosed a thalamic ischemic lesion on neuroimaging.This case report highlights the importance of performing neuroradiologic screening in the emergency department even when clinical history and physical findings are highly suggestive for transient global amnesia.

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.

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

Synonymies of wasp-mimicking species within the katydid genus Aganacris (Orthoptera: Tettigoniidae: Phaneropterinae)

USDA-ARS?s Scientific Manuscript database

Five neotropical wasp-mimicking species of the genus Aganacris—two known from females only and three from males only—are reviewed. Based on observations of interspecific interactions and morphological comparisons, sexual dimorphism is shown to occur within species, and that female species are consp...

Amplified biosensing using the horseradish peroxidase-mimicking DNAzyme as an electrocatalyst.

PubMed

Pelossof, Gilad; Tel-Vered, Ran; Elbaz, Johann; Willner, Itamar

2010-06-01

The hemin/G-quadruplex horseradish peroxidase-mimicking DNAzyme is assembled on Au electrodes. It reveals bioelectrocatalytic properties and electrocatalyzes the reduction of H(2)O(2). The bioelectrocatalytic functions of the hemin/G-quadruplex DNAzyme are used to develop electrochemical sensors that follow the activity of glucose oxidase and biosensors for the detection of DNA or low-molecular-weight substrates (adenosine monophosphate, AMP). Hairpin nucleic structures that include the G-quadruplex sequence in a caged configuration and the nucleic acid sequence complementary to the analyte DNA, or the aptamer sequence for AMP, are immobilized on Au-electrode surfaces. In the presence of the DNA analyte, or AMP, the hairpin structures are opened, and the hemin/G-quadruplex horseradish peroxidase-mimicking DNAzyme structures are generated on the electrode surfaces. The bioelectrocatalytic cathodic currents generated by the functionalized electrodes, upon the electrochemical reduction of H(2)O(2), provide a quantitative measure for the detection of the target analytes. The DNA target was analyzed with a detection limit of 1 x 10(-12) M, while the detection limit for analyzing AMP was 1 x 10(-6) M. Methods to regenerate the sensing surfaces are presented.

Idelalisib-induced colitis and skin eruption mimicking graft-versus-host disease.

PubMed

Hammami, Muhammad Bader; Al-Taee, Ahmad; Meeks, Marshall; Fesler, Mark; Hurley, M Yadira; Cao, Dengfeng; Lai, Jin-Ping

2017-04-01

Idelalisib is a selective inhibitor of the delta isoform of phosphatidylinositol 3-kinase which was approved by the United States Federal Drug Administration in 2014 for the treatment of relapsed chronic lymphocytic leukemia and indolent non-Hodgkin lymphoma. Drug-induced injury of the gastrointestinal tract is a relatively frequent but usually under-recognized disease entity. We report the case of a 56-year-old male with a history of relapsed follicular lymphoma status post allogenic bone marrow transplant who developed severe diarrhea with a skin eruption mimicking graft-versus-host disease (GVHD) 6 months after starting idelalisib. He underwent a colonoscopy demonstrating a grossly normal-appearing colon and terminal ileum. Biopsies taken during the procedure revealed mild active ileitis, colitis, and proctitis with frequent epithelial apoptosis, and focal intra-epithelial lymphocytosis. Skin biopsies revealed sub-acute spongiotic dermatitis suggestive of either contact dermatitis or an eczematous drug reaction. Symptoms were attributed to idelalisib given their resolution with withdrawal of the drug in conjunction with the skin and colonic biopsies. High clinical suspicion and awareness of the histological features of idelalisib-associated colitis is important to distinguish it from potential mimickers such as GVHD and infectious colitis.

Electrochemically controlled drug-mimicking protein release from iron-alginate thin-films associated with an electrode.

PubMed

Jin, Zhiyuan; Güven, Güray; Bocharova, Vera; Halámek, Jan; Tokarev, Ihor; Minko, Sergiy; Melman, Artem; Mandler, Daniel; Katz, Evgeny

2012-01-01

Novel biocompatible hybrid-material composed of iron-ion-cross-linked alginate with embedded protein molecules has been designed for the signal-triggered drug release. Electrochemically controlled oxidation of Fe(2+) ions in the presence of soluble natural alginate polymer and drug-mimicking protein (bovine serum albumin, BSA) results in the formation of an alginate-based thin-film cross-linked by Fe(3+) ions at the electrode interface with the entrapped protein. The electrochemically generated composite thin-film was characterized by electrochemistry and atomic force microscopy (AFM). Preliminary experiments demonstrated that the electrochemically controlled deposition of the protein-containing thin-film can be performed at microscale using scanning electrochemical microscopy (SECM) as the deposition tool producing polymer-patterned spots potentially containing various entrapped drugs. Application of reductive potentials on the modified electrode produced Fe(2+) cations which do not keep complexation with alginate, thus resulting in the electrochemically triggered thin-film dissolution and the protein release. Different experimental parameters, such as the film-deposition time, concentrations of compounds and applied potentials, were varied in order to demonstrate that the electrodepositon and electrodissolution of the alginate composite film can be tuned to the optimum performance. A statistical modeling technique was applied to find optimal conditions for the formation of the composite thin-film for the maximal encapsulation and release of the drug-mimicking protein at the lowest possible potential. © 2011 American Chemical Society

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

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.

A High-Grade Chondrosarcoma of Calcaneum Mimicking as a Benign Pathology: Delayed Diagnosis and Management.

PubMed

Baba, Muzamil Ahmad; Nazir, Naila; Shabeer, Maajid; Mir, Bashir Ahmed; Kawoosa, Altaf Ahmad

2016-10-01

This case is presented to highlight a rare case of chondrosarcoma of calcaneum in a young adult mimicking as a benign pathology and to highlight the diagnosis and early management of such cases to prevent complications and even death. Chondrosarcoma constitutes less than 10% of all primary malignancies of bone and occurs mostly in proximal locations such as pelvis, proximal femur, and proximal humerus. We present a case of high-grade chondrosarcoma at a very rare site, calcaneum of a 40-year-old male that was mimicking as a benign pathology. This case report highlights the importance of proper clinical examination, evaluation, and suspicion for benign occurring lesions to prevent complications related to a delay in diagnosis. Therapeutic, Level IV: Case study. © 2016 The Author(s).

Primary adnexial hydatid cyst mimicking ovarian tumor

PubMed Central

Görgen, Hüsnü; Api, Murat; Çetin, Ahmet

2009-01-01

We report here the rare case of a 28-year-old woman with a large hydatid cyst in her left lower pelvis with an unusual sonographic presentation mimicking a multicystic ovarian tumor. Laparoscopic evaluation revealed normal uterus and ovaries with a swelling in the left retropritoneal area. We decided to reach this tumour by the vaginal route and multiple scolex, daughter cysts were removed via a left lateral vaginal wall incision. The pericystic cavity was thoroughly washed. The patient was discharged on the first postoperative day. Mebendazole (100 mg twice daily) was administered for 4 months. This parasite should be kept in mind and considered when making the differential diagnosis of pelvic cystic masses, particularly if the patient is from an endemic area. PMID:24591878

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.

Exquisite Enzyme-Fenton Biomimetic Catalysts for Hydroxyl Radical Production by Mimicking an Enzyme Cascade.

PubMed

Zhang, Qi; Chen, Shuo; Wang, Hua; Yu, Hongtao

2018-03-14

Hydrogen peroxide (H 2 O 2 ) is a key reactant in the Fenton process. As a byproduct of enzymatic reaction, H 2 O 2 can be obtained via catalytical oxidation of glucose using glucose oxidase in the presence of O 2 . Another oxidation product (gluconic acid) can suitably adjust the microenvironmental pH contributing to the Fe 3+ /Fe 2+ cycle in the Fenton reaction. Enzymes are extremely efficient at catalyzing a variety of reactions with high catalytic activity, substrate specificity, and yields in living organisms. Inspired by the multiple functions of natural multienzyme systems, an exquisite nanozyme-modified α-FeOOH/porous carbon (PC) biomimetic catalyst constructed by in situ growth of glucose oxidase-mimicking Au nanoparticles and crystallization of adsorbed ferric ions within carboxyl into hierarchically PC is developed as an efficient enzyme-Fenton catalyst. The products (H 2 O 2 , ∼4.07 mmol·L -1 ) of the first enzymatic reaction are immediately used as substrates for the second Fenton-like reaction to generate the valuable • OH (∼96.84 μmol·L -1 ), thus mimicking an enzyme cascade pathway. α-FeOOH nanocrystals, attached by C-O-Fe bondings, are encapsulated into the mesoporous PC frameworks, facilitating the electron transfer between α-FeOOH and the PC support and greatly suppressing iron leaching. This study paves a new avenue for designing biomimetic enzyme-based Fenton catalysts mimicking a natural system for • OH production.

[Graft-versus-host disease as the cause of symptoms mimicking Sjögren's syndrome].

PubMed

Tuchocka-Piotrowska, Aleksandra; Puszczewicz, Mariusz; Kołczewska, Aleksandra; Majewski, Dominik

2006-01-01

A case of chronic graft-versus-host disease (chronic GvHD) mimicking symptoms associated with idiopathic Sjögren's syndrome is presented. Hypotheses on the pathophysiological origin of clinical syndromes associated with graft-versus-host disease are discussed.

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.

Addison’s Disease Mimicking as Acute Pancreatitis: A Case Report

PubMed Central

Chaudhuri, Sayani; Rao, Karthik N; Ommurugan, Balaji; Varghese, George

2017-01-01

Over past two decades there has been significant improvement in medical field in elucidating the underlying pathophysiology and genetics of Addison’s disease. Adrenal insufficiency (Addison’s disease) is a rare disease with an incidence of 0.8/100,000 cases. The diagnosis may be delayed if the clinical presentation mimics a gastrointestinal disorder or psychiatric illness. We report a case of Addison’s disease presenting as acute pain in abdomen mimicking clinical presentation of acute pancreatitis. PMID:28571196

Metastatic carcinoma to the mandible that mimicked pulpal/periodontal disease.

PubMed

Selden, H S; Manhoff, D T; Hatges, N A; Michel, R C

1998-04-01

An oral cavity metastasis from a poorly differentiated carcinoma, presumed to have originated in the pancreas, mimicked a dental abscess. An additional metastasis to the lung caused a postobstructive lobar pneumonia that masked the lesion, thereby delaying the diagnosis of malignancy. This case report illustrates how the clinical manifestations of a widely disseminated neoplasm led to initial medical confusion and subsequent dental misdiagnosis, and serves to caution of a possible pitfall in the dental evaluation of endodontic lesions.

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

Lung Metastasis Mimicking Fingertip Infection

PubMed Central

Soylemez, Salih; Demiroglu, Murat; Yayla, Mehmet Ali; Ozkan, Korhan; Alpan, Bugra; Ozger, Harzem

2015-01-01

Metastasis fingers (acral metastasis) are finding a poor prognosis. Past medical history should be questioned and metastasis from primary tumor should be kept in mind in patients with pain, swelling, and hyperemia in fingers. Successful surgical treatment on acral metastasis does not extend the life expectancy; however, it reduces the patient's pain during his terminal period, saves the functions of the limb, and increases life comfort. PMID:26236517

Simple bone cyst of mandible mimicking periapical cyst

PubMed Central

HS, Charan Babu; Rai, Bhagawan Das; Nair, Manju A.; Astekar, Madhusudan S.

2012-01-01

Simple bone cysts (SBC) are pseudocysts occurring less commonly in the maxillofacial region. The uncertain and unclear etiopathogenesis led to numerous synonyms to refer this particular cyst. These cysts are devoid of an epithelial lining and are usually empty or contain blood or straw-colored fluid. In jaws initially it mimics a periapical cyst and later can lead to cortical bone expansion warranting for radical approach, which is seldom required. SBC is predominantly diagnosed in first two decades of life. Here we report a case of solitary bone cyst mimicking a periapical cyst of a mandibular molar in a 37-year-old patient. PMID:24765458

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.

Intraepithelial lymphocytes, scores, mimickers and challenges in diagnosing gluten-sensitive enteropathy (celiac disease)

PubMed Central

Sergi, Consolato; Shen, Fan; Bouma, Gerd

2017-01-01

The upper digestive tract is routinely scoped for several causes of malabsorption, and the number of duodenal biopsy specimens has increased notably in the last 10 years. Gluten-sensitive enteropathy (GSE) is an autoimmune disease, which shows an increasing prevalence worldwide and requires a joint clinico-pathological approach. The classical histopathology of GSE with partial or total villous blunting is well recognized, but the classification of GSE is not straightforward. Moreover, several mimickers of GSE with intraepithelial lymphocytosis have been identified in the last 20 years, with drug interactions and medical comorbidities adding to the conundrum. In this review, we report on the normal duodenal mucosa, the clinical presentation and laboratory diagnosis of GSE, the duodenal intraepithelial lymphocytes and immunophenotype of GSE-associated lymphocytes, the GSE mimickers, the differences “across oceans” among guidelines in diagnosing GSE, and the use of a synoptic report for reporting duodenal biopsies in both children and adults in the 21st century. PMID:28216964

Super-Anticoagulant Heparin-Mimicking Hydrogel Thin Film Attached Substrate Surfaces to Improve Hemocompatibility.

PubMed

He, Min; Cui, Xiaofei; Jiang, Huiyi; Huang, Xuelian; Zhao, Weifeng; Zhao, Changsheng

2017-02-01

In this study, heparin-mimicking hydrogel thin films are covalently attached onto poly(ether sulfone) membrane surfaces to improve anticoagulant property. The hydrogel films display honeycomb-like porous structure with well controlled thickness and show long-term stability. After immobilizing the hydrogel films, the membranes show excellent anticoagulant property confirmed by the activated partial thromboplastin time values exceeding 600 s. Meanwhile, the thrombin time values increase from 20 to 61 s as the sodium allysulfonate proportions increase from 0 to 80 mol%. In vitro investigations of protein adsorption and blood-related complement activation also confirm that the membranes exhibit super-anticoagulant property. Furthermore, gentamycin sulfate is loaded into the hydrogel films, and the released drug shows significant inhibition toward E. coli bacteria. It is believed that the surface attached heparin-mimicking hydrogel thin films may show high potential for the applications in various biological fields, such as blood contacting materials and drug loading materials. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

A case of chronic active Epstein-Barr virus infection mimicking adult-onset Still's disease.

PubMed

Yoshioka, Katsunobu; Fukushima, Hiroko; Ishii, Naomi; Kita, Akiko; Hanioka, Yusuke; Minami, Mieko; Inoue, Takeshi; Yamagami, Keiko

2013-01-01

An 83-year-old man was diagnosed with adult-onset Still's disease (AOSD) based on clinical and laboratory findings. However, glucocorticoid had little effect. Epstein-Barr virus (EBV)-DNA was detected in peripheral blood, and autopsy findings confirmed a diagnosis of chronic active EBV infection (CAEBV). CAEBV mimics AOSD, and the presence of articular involvement and leukocytosis does not exclude the possibility of CAEBV. CAEBV should be included in the differential diagnosis of AOSD, and measurement of EBV-DNA is essential.

Tinea capitis-like infection caused by Rhodotorula mucilaginosa in a shelter for African Refugee Children in Northern Israel.

PubMed

Peretz, Avi; Nitzan, Orna; Freidus, Victoria; Kassem, Riad

2018-03-01

Rhodotorula is a genus of unicellular pigmented yeasts, part of the division Basidiomycota. In this article, we report three cases of refugee children in a day care shelter in northern Israel who were clinically diagnosed and treated empirically as with ringworm infection but with clean and exclusive growth of Rhodotorula mucilaginosa in repeated cultures of several skin samples. Skin infections caused by this yeast are rare and there are few reports in the literature, mainly in patients who are immunocompromised. Here we report an infectious process of the scalp in immunocompetent children, caused by Rhodotorula mucilaginosa mimicking tinea capitis. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Developing Autonomous Vehicles That Learn to Navigate by Mimicking Human Behavior

DTIC Science & Technology

2006-09-28

navigate in an unstructured environment to a specific target or location. 15. SUBJECT TERMS autonomous vehicles , fuzzy logic, learning behavior...ANSI-Std Z39-18 Developing Autonomous Vehicles That Learn to Navigate by Mimicking Human Behavior FINAL REPORT 9/28/2006 Dean B. Edwards Department...the future, as greater numbers of autonomous vehicles are employed, it is hoped that lower LONG-TERM GOALS Use LAGR (Learning Applied to Ground Robots

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

Novel orally available salvinorin A analog PR-38 inhibits gastrointestinal motility and reduces abdominal pain in mouse models mimicking irritable bowel syndrome.

PubMed

Sałaga, M; Polepally, P R; Sobczak, M; Grzywacz, D; Kamysz, W; Sibaev, A; Storr, M; Do Rego, J C; Zjawiony, J K; Fichna, J

2014-07-01

The opioid and cannabinoid systems play a crucial role in multiple physiological processes in the central nervous system and in the periphery. Selective opioid as well as cannabinoid (CB) receptor agonists exert a potent inhibitory action on gastrointestinal (GI) motility and pain. In this study, we examined (in vitro and in vivo) whether PR-38 (2-O-cinnamoylsalvinorin B), a novel analog of salvinorin A, can interact with both systems and demonstrate therapeutic effects. We used mouse models of hypermotility, diarrhea, and abdominal pain. We also assessed the influence of PR-38 on the central nervous system by measurement of motoric parameters and exploratory behaviors in mice. Subsequently, we investigated the pharmacokinetics of PR-38 in mouse blood samples after intraperitoneal and oral administration. PR-38 significantly inhibited mouse colonic motility in vitro and in vivo. Administration of PR-38 significantly prolonged the whole GI transit time, and this effect was mediated by µ- and κ-opioid receptors and the CB1 receptor. PR-38 reversed hypermotility and reduced pain in mouse models mimicking functional GI disorders. These data expand our understanding of the interactions between opioid and cannabinoid systems and their functions in the GI tract. We also provide a novel framework for the development of future potential treatments of functional GI disorders. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

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.

Chitosan-based coatings in the prevention of intravascular catheter-associated infections.

PubMed

Mendoza, Gracia; Regiel-Futyra, Anna; Tamayo, Alejandra; Monzon, Marta; Irusta, Silvia; de Gregorio, Miguel Angel; Kyzioł, Agnieszka; Arruebo, Manuel

2018-01-01

Central venous access devices play an important role in patients with prolonged intravenous administration requirements. In the last years, the coating of these devices with bactericidal compounds has emerged as a potential tool to prevent bacterial colonization. Our study describes the modification of 3D-printed reservoirs and silicone-based catheters, mimicking central venous access devices, through different approaches including their coating with the well known biocompatible and bactericidal polymer chitosan, with the anionic polysaccharide alginate; also, plasma treated surfaces were included in the study to promote polymer adhesion. The evaluation of the antimicrobial action of those surface modifications compared to that exerted by a model antibiotic (ciprofloxacin) adsorbed on the surface of the devices was carried out. Surface characterization was developed by different methodologies and the bactericidal effects of the different coatings were assayed in an in vitro model of Staphylococcus aureus infection. Our results showed a significant reduction in the reservoir roughness (≤73%) after coating though no changes were observed for coated catheters which was also confirmed by scanning electron microscopy, pointing to the importance of the surface device topography for the successful attachment of the coating and for the subsequent development of bactericidal effects. Furthermore, the single presence of chitosan on the reservoirs was enough to fully inhibit bacterial growth exerting the same efficiency as that showed by the model antibiotic. Importantly, chitosan coating showed low cytotoxicity against human keratinocytes, human lung adenocarcinoma epithelial cells, and murine colon carcinoma cells displaying viability percentages in the range of the control samples (>95%). Chitosan-based coatings are proposed as an effective and promising solution in the prevention of microbial infections associated to medical devices.

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.

Severe cytomegalovirus infections in immunocompetent patients at admission as dengue mimic: successful treatment with intravenous ganciclovir.

PubMed

Tirumala, Suhasini; Behera, Bijayini; Lingala, Shilpa; Kumar, B Vijay; Mishra, Pradeep Kumar; Gurunath, J M; HariCharan; Kartik; Naresh

2012-11-01

Cytomegalovirus (CMV) infection is associated with adverse clinical outcomes in immunosuppressed persons. The incidence and association of CMV reactivation with adverse clinical outcomes in critically ill persons lacking evidence of immunosuppression at ICU admission has received great attention in the practice of critical care medicine. Critically ill patients in ICU who had associated risk factors such as mechanical ventilation, severe sepsis, or blood transfusion are more prone to CMV activation, which in turn led to increased mortality and morbidity in terms of increased ICU stay, longer duration of mechanical ventilation, and higher rates of nosocomial infections. However, severe CMV as initial presentation mimicking dengue infection is rare. We recently came across seven cases with positive CMV serology at ICU admission, which we discuss in the light of current literature. Copyright © 2012 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Primary scattered multifocal melanocytomas in spinal canal mimicking neurofibromatosis.

PubMed

Yang, Chenlong; Fang, Jingyi; Li, Guang; Yang, Jun; Xu, Yulun

2016-08-01

Meningeal melanocytoma is an extremely rare pigmented tumor derived from leptomeningeal melanocytes. By and large, it is considered to be a well-differentiated and slow-growing benign lesion. Generally, meningeal melanocytomas are solitary lesions, and the occurrence of the primary multifocal form in the central nervous system is exceedingly rare; it has been previously reported in only six cases. The present report illustrates a 41-year-old woman with primary multifocal meningeal melanocytoma in the spinal canal. Contrary to earlier reports, the tumors presented with a scattered appearance mimicking neurofibromatosis. This study is a case report and review of literature. On admission, the cerebral magnetic resonance images of the patient were normal, whereas the spinal magnetic resonance images showed scattered multifocal nodules mimicking neurofibromatosis. Surgical resection of the responsible lesions was scheduled. In addition to this case presentation, relevant previous reports were reviewed, and the challenging diagnosis, management, and prognosis of meningeal melanocytoma are discussed. Gross total resection of the two largest lesions was achieved, and histopathological examinations confirmed the diagnosis. Despite the benign histopathological findings, the patient had an aggressive clinical course. On follow-up at 18 months after surgery, she succumbed to the disease. Clinicians should be alert to a potential aggressive clinical course of meningeal melanocytoma, despite its benign histopathological nature. Of particular note is multifocality and diffuse leptomeningeal hyperpigmentation, which may suggest a poor prognosis. A combined treatment including surgical resection and adjuvant radiotherapy should be considered, and long-term close follow-up is necessary. Copyright © 2016. Published by Elsevier Inc.

Synthetic mimicking of plant oils and comparison with naturally grown products in polyurethane synthesis.

PubMed

Coles, Stuart R; Barker, Guy; Clark, Andrew J; Kirwan, Kerry; Jacobs, Daniel; Makenji, Kylash; Pink, David

2008-06-11

The use of plant oils as industrial feedstocks can often be hampered by their lack of optimization towards a particular process, as well as their development being risky; growing suitable volumes of crops to test can take up to five years. To circumvent this, we aimed to discover a method that would mimic plant oil profiles in the laboratory, and show that they exhibited similar properties to the naturally grown plant oils in a given process. Using the synthesis of polyurethanes as an example, we have synthesized six different polymers and demonstrated that plant oils will produce polymers with similar physical properties to those oils mimicked in the laboratory. The use of this mimicking process can be extended to other types of polymers to obtain a method for predicting the properties of a given material based on the plant oil composition of a crop before it is grown in bulk.

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.

Endometriosis after surgical menopause mimicking pelvic malignancy: surgeons' predicament.

PubMed

Bhat, Rani A; Teo, Melissa; Bhat, Akhil Krishnanand

2014-05-01

Prevalence of persistent endometriosis in women after menopause without any hormonal replacement therapy is very rare. This is a case of a woman with previous history of total hysterectomy and bilateral salpingo-oophorectomy for endometriosis who presented with hemoperitoneum, vaginal bleeding, pelvic mass, and pulmonary thromboembolism mimicking as rectovaginal septum carcinoma. This is the first case report with a unique mode of presentation wherein the patient presented with hemoperitoneum requiring emergency embolization of the vessel to stabilize the patient. She underwent en bloc resection of the tumor with high anterior resection of the rectum. Histopathology confirmed endometriosis.

Endometriosis After Surgical Menopause Mimicking Pelvic Malignancy: Surgeons’ Predicament

PubMed Central

Bhat, Rani A.; Teo, Melissa; Bhat, Akhil Krishnanand

2014-01-01

Prevalence of persistent endometriosis in women after menopause without any hormonal replacement therapy is very rare. This is a case of a woman with previous history of total hysterectomy and bilateral salpingo-oophorectomy for endometriosis who presented with hemoperitoneum, vaginal bleeding, pelvic mass, and pulmonary thromboembolism mimicking as rectovaginal septum carcinoma. This is the first case report with a unique mode of presentation wherein the patient presented with hemoperitoneum requiring emergency embolization of the vessel to stabilize the patient. She underwent en bloc resection of the tumor with high anterior resection of the rectum. Histopathology confirmed endometriosis. PMID:24936277

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

High-altitude cerebral oedema mimicking stroke.

PubMed

Yanamandra, Uday; Gupta, Amul; Patyal, Sagarika; Varma, Prem Prakash

2014-03-26

High-altitude cerebral oedema (HACO) is the most fatal high-altitude illness seen by rural physicians practising in high-altitude areas. HACO presents clinically with cerebellar ataxia, features of raised intracranial pressure (ICP) and coma. Early identification is important as delay in diagnosis can be fatal. We present two cases of HACO presenting with focal deficits mimicking stroke. The first patient presented with left-sided hemiplegia associated with the rapid deterioration in the sensorium. Neuroimaging revealed features suggestive of vasogenic oedema. The second patient presented with monoplegia of the lower limb. Neuroimaging revealed perfusion deficit in anterior cerebral artery territory. Both patients were managed with dexamethasone and they improved dramatically. Clinical picture and neuroimaging closely resembled acute ischaemic stroke in both cases. Thrombolysis in these patients would have been disastrous. Recent travel to high altitude, young age, absence of atherosclerotic risk factors and features of raised ICP concomitantly directed the diagnosis to HACO.

[A giant myxoid leiomyoma mimicking an inguinal hernia].

PubMed

Huszár, Orsolya; Zaránd, Attila; Szántó, Gyöngyi; Juhász, Viktória; Székely, Eszter; Novák, András; Molnár, Béla Ákos; Harsányi, László

2016-03-06

Leiomyoma is a rare, smooth muscle tumour that can occur everywhere in the human body. The authors present the history of a 60-year-old female, who had a giant, Mullerian type myxoid leiomyoma in the inguinal region mimicking acute abdominal symptoms. After examination the authors removed the soft tissue mass in the right femoral region reaching down in supine position to the middle third of the leg measuring 335 × 495 × 437 mm in greatest diameters in weight 33 kg. Reconstruction of the tissue defect was performed using oncoplastic guidelines. During the follow-up time no tumour recurrence was detected and the quality of life of the patient improved significantly.

Enterobiasis in Ectopic Locations Mimicking Tumor-Like Lesions

PubMed Central

Pampiglione, Silvio; Rivasi, Francesco

2009-01-01

Both the clinical and the histopathological diagnostic difficulties of oxyuriasis in unusual sites and their importance from a clinical point of view are pointed out. The authors report two ectoptic cases of enterobiasis observed in Northern Italy, one located in a fallopian tube of a 57-year-old woman and the other in a perianal subcutaneous tissue of a 59-year-old man, mimicking tumor-like lesions. The authors take advantage of the occasion to focus the attention of the medical world on this subject, lamenting the scarce importance given to this parasitosis in university courses of medical schools and in medical textbooks as it is incorrectly considered “out-of-fashion.” PMID:20016678

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

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.

Extraventricular neurocytoma in a child mimicking oligodendroglioma: a diagnostic pitfall.

PubMed

Limaiem, F; Bellil, S; Chelly, I; Mekni, A; Bellil, K; Jemel, H; Haouet, S; Zitouna, M; Kchir, N

2009-04-01

Extraventricular neurocytomas are rare neuronal tumours that have been included in the 2007 WHO classification as a variant of central neurocytoma. They arise outside the ventricles, usually within the cerebral hemisphere,s but also in other regions throughout the neuraxis. The morphological overlap of these tumours with oligodendroglioma often poses diagnostic difficulty. Herein, a case of extraventricular neurocytoma in a 4-year-old girl is reported that mimicked histologically oligodendroglioma. The authors describe the clinicopathological features of this rare entity with special emphasis on differential diagnosis.

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

Enterobius vermicularis: A Cause of Abdominal Pain Mimicking Acute Appendicitis in Children. A Retrospective Cohort Study.

PubMed

Zouari, Mohamed; Louati, Hamid; Abid, Imen; Trabelsi, Fatma; Ben Dhaou, Mahdi; Jallouli, Mohamed; Mhiri, Riadh

2018-02-01

Enterobius vermicularis (EV) is the most common helminthic infection in the world. This small parasite is predominant in the pediatric population. The presence of EV in the appendix can cause or mimick appendicitis. The aim of our study was to compare patients with EV infection and those without EV infection, and to identify predictive factors that may help the diagnosis of EV infection in patients presenting with right iliac fossa pain and avoid negative appendectomy. A retrospective analysis of all the appendices removed between January 2012 and December 2016 was conducted at the department of pediatric surgery, Hedi Chaker Hospital, Sfax, Tunisia. According to the final histopathological diagnosis, patients with EV infection were compared to those without EV infection. Data including age, sex, white blood cell (WBC) count, neutrophil count, eosinophil count, C-reactive protein, and ultrasound results for both groups were analyzed and compared. The study protocol was approved by the local hospital ethics committee. Statistical analysis was performed using IBM SPSS, version 20. Descriptive analysis in the form of mean and standard deviation was performed on demographic information. Differences between groups were assessed using the student t-test for continuous variables and the χ2 test and Fisher exact test where appropriate for categorical variables. In total, 540 pediatric appendectomies were performed. Overall, 63.5% of patients were male and 36.5% were female. Mean age was 9.28 ± 2.77 years. 22.2% of procedures were completed laparoscopically, 76.5% were open and 1.3% were converted. The negative appendectomy rate was 11.1%. EV was present in 9.8% of cases. Comparison of clinical, biological, and ultrasound findings between two groups of patients with EV (EV+) and those without EV (EV-) shows a statistical significance for pruritus ani (P < 0.001), WBC count (P < 0.001), neutrophil count (P < 0.001), C-reactive protein (CRP) (P = 0.001), positive ultrasound

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.

Mimicking the extracellular matrix with functionalized, metal-assembled collagen peptide scaffolds.

PubMed

Hernandez-Gordillo, Victor; Chmielewski, Jean

2014-08-01

Natural and synthetic three-dimensional (3-D) scaffolds that mimic the microenvironment of the extracellular matrix (ECM), with growth factor storage/release and the display of cell adhesion signals, offer numerous advantages for regenerative medicine and in vitro morphogenesis and oncogenesis modeling. Here we report the design of collagen mimetic peptides (CMPs) that assemble into a highly crosslinked 3-D matrix in response to metal ion stimuli, that may be functionalized with His-tagged cargoes, such as green fluorescent protein (GFP-His8) and human epidermal growth factor (hEGF-His6). The bound hEGF-His6 was found to gradually release from the matrix in vitro and induce cell proliferation in the EGF-dependent cell line MCF10A. The additional incorporation of a cell adhesion sequence (RGDS) at the N-terminus of the CMP creates an environment that facilitated the organization of matrix-encapsulated MCF10A cells into spheroid structures, thus mimicking the ECM environment. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

Tissue mimicking simulations for temporal enhanced ultrasound-based tissue typing

NASA Astrophysics Data System (ADS)

Bayat, Sharareh; Imani, Farhad; Gerardo, Carlos D.; Nir, Guy; Azizi, Shekoofeh; Yan, Pingkun; Tahmasebi, Amir; Wilson, Storey; Iczkowski, Kenneth A.; Lucia, M. Scott; Goldenberg, Larry; Salcudean, Septimiu E.; Mousavi, Parvin; Abolmaesumi, Purang

2017-03-01

Temporal enhanced ultrasound (TeUS) is an imaging approach where a sequence of temporal ultrasound data is acquired and analyzed for tissue typing. Previously, in a series of in vivo and ex vivo studies we have demonstrated that, this approach is effective for detecting prostate and breast cancers. Evidences derived from our experiments suggest that both ultrasound-signal related factors such as induced heat and tissue-related factors such as the distribution and micro-vibration of scatterers lead to tissue typing information in TeUS. In this work, we simulate mechanical micro-vibrations of scatterers in tissue-mimicking phantoms that have various scatterer densities reflecting benign and cancerous tissue structures. Finite element modeling (FEM) is used for this purpose where the vertexes are scatterers representing cell nuclei. The initial positions of scatterers are determined by the distribution of nuclei segmented from actual digital histology scans of prostate cancer patients. Subsequently, we generate ultrasound images of the simulated tissue structure using the Field II package resulting in a temporal enhanced ultrasound. We demonstrate that the micro-vibrations of scatterers are captured by temporal ultrasound data and this information can be exploited for tissue typing.

Nontuberculous mycobacterial infection with concurrent IgG4-related lymphadenopathy.

PubMed

Liu, Ting-Ting; Weng, Shao-Wen; Wang, Ming-Chung; Huang, Wan-Ting

2016-03-01

Disseminated nontuberculous mycobacteria (NTM) infection with concurrent IgG4-related lymphadenopathy has not been reported. We described a patient with neutralizing autoantibodies to interferon-gamma (IFN-γ) and elevated levels of serum IgG4 presenting with generalized lymphadenopathy and reactive dermatosis. Histologically, lymph nodes (LNs) showed effaced nodal architecture with polymorphic infiltrates, mimicking angioimmunoblastic T-cell lymphoma. Both the absolute number and the ratio of IgG4+ plasma cells to IgG+ plasma cells were increased. Mycobacterium abscessus was isolated from cultures of LNs, and demonstrated by polymerase chain reaction-restriction fragment length polymorphism. The skin biopsy showed neutrophilic dermatosis, consistent with Sweet syndrome. The patient met the criteria of both adult-onset immunodeficiency syndrome and IgG4-related lymphadenopathy. This case provides evidence of disseminated NTM infection with concurrent type III IgG4-related lymphadenopathy in the patient with anti-IFN-γ autoantibodies. © 2015 APMIS. Published by John Wiley & Sons Ltd.

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

Case report: vertebral foreign body granuloma mimicking a skeletal metastasis.

PubMed

Vossen, Josephina A; Bathaii, Seyed M; Hatfield, Bryce; Hayes, Curtis W

2018-06-01

Intraosseous foreign body granuloma formation related to migrated surgical material is a rarely reported condition with variable imaging appearance. In this case report, we describe a foreign body granuloma that occurred in a lumbar vertebral body one level above a prior surgical fusion. The lytic appearance mimicked a skeletal metastasis in a 65-year-old patient with recently diagnosed renal cell carcinoma. To the best of our knowledge, this is the first reported case of a lumbar vertebral foreign body granuloma occurring distant from the site of surgery, indistinguishable from skeletal metastasis on radiologic examination.

Unusual Case of Overt Aortic Dissection Mimicking Aortic Intramural Hematoma

PubMed Central

Disha, Kushtrim; Kuntze, Thomas; Girdauskas, Evaldas

2016-01-01

We report an interesting case in which overt aortic dissection mimicked two episodes of aortic intramural hematoma (IMH) (Stanford A, DeBakey I). This took place over the course of four days and had a major influence on the surgical treatment strategy. The first episode of IMH regressed completely within 15 hours after it was clinically diagnosed and verified using imaging techniques. The recurrence of IMH was detected three days thereafter, resulting in an urgent surgical intervention. Overt aortic dissection with evidence of an intimal tear was diagnosed intraoperatively. PMID:27066437

Testicular Schistosomiasis Mimicking Malignancy in a Child: A Case Report.

PubMed

Ekenze, Sebastian O; Modekwe, Victor O; Nzegwu, Martin A; Ekpemo, Samuel C; Ezomike, Uchechukwu O

2015-08-01

Schistosomiasis is an important communicable disease in the developing world. However, testicular schistosomiasis is an extremely rare condition. We report a case of testicular schistosomiasis mimicking testicular tumour in a 13 year old who presented with huge unilateral testicular mass. The dilemma encountered in the diagnosis and treatment of this child is presented to highlight the need for high index of suspicion of this pathology in children with testicular mass presenting from schistosomiasis-endemic areas. © The Author [2015]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Tissue mimicking materials for the detection of prostate cancer using shear wave elastography: a validation study.

PubMed

Cao, Rui; Huang, Zhihong; Varghese, Tomy; Nabi, Ghulam

2013-02-01

Quantification of stiffness changes may provide important diagnostic information and aid in the early detection of cancers. Shear wave elastography is an imaging technique that assesses tissue stiffness using acoustic radiation force as an alternate to manual palpation reported previously with quasistatic elastography. In this study, the elastic properties of tissue mimicking materials, including agar, polyacrylamide (PAA), and silicone, are evaluated with an objective to determine material characteristics which resemble normal and cancerous prostate tissue. Acoustic properties and stiffness of tissue mimicking phantoms were measured using compressional mechanical testing and shear wave elastography using supersonic shear imaging. The latter is based on the principles of shear waves generated using acoustic radiation force. The evaluation included tissue mimicking materials (TMMs) within the prostate at different positions and sizes that could mimic cancerous and normal prostate tissue. Patient data on normal and prostate cancer tissues quantified using biopsy histopathology were used to validate the findings. Pathologist reports on histopathology were blinded to mechanical testing and elastographic findings. Young's modulus values of 86.2 ± 4.5 and 271.5 ± 25.7 kPa were obtained for PAA mixed with 2% Al(2)O(3) particles and silicone, respectively. Young's modulus of TMMs from mechanical compression testing showed a clear trend of increasing stiffness with an increasing percentage of agar. The silicone material had higher stiffness values when compared with PAA with Al(2)O(3). The mean Young's modulus value in cancerous tissue was 90.5 ± 4.5 kPa as compared to 93.8 ± 4.4 and 86.2 ± 4.5 kPa obtained with PAA with 2% Al(2)O(3) phantom at a depth of 52.4 and 36.6 mm, respectively. PAA mixed with Al(2)O(3) provides the most suitable tissue mimicking material for prostate cancer tumor material, while agar could form the surrounding background to simulate normal

Tissue mimicking materials for the detection of prostate cancer using shear wave elastography: A validation study

PubMed Central

Cao, Rui; Huang, Zhihong; Varghese, Tomy; Nabi, Ghulam

2013-01-01

Purpose: Quantification of stiffness changes may provide important diagnostic information and aid in the early detection of cancers. Shear wave elastography is an imaging technique that assesses tissue stiffness using acoustic radiation force as an alternate to manual palpation reported previously with quasistatic elastography. In this study, the elastic properties of tissue mimicking materials, including agar, polyacrylamide (PAA), and silicone, are evaluated with an objective to determine material characteristics which resemble normal and cancerous prostate tissue. Methods: Acoustic properties and stiffness of tissue mimicking phantoms were measured using compressional mechanical testing and shear wave elastography using supersonic shear imaging. The latter is based on the principles of shear waves generated using acoustic radiation force. The evaluation included tissue mimicking materials (TMMs) within the prostate at different positions and sizes that could mimic cancerous and normal prostate tissue. Patient data on normal and prostate cancer tissues quantified using biopsy histopathology were used to validate the findings. Pathologist reports on histopathology were blinded to mechanical testing and elastographic findings. Results: Young's modulus values of 86.2 ± 4.5 and 271.5 ± 25.7 kPa were obtained for PAA mixed with 2% Al2O3 particles and silicone, respectively. Young's modulus of TMMs from mechanical compression testing showed a clear trend of increasing stiffness with an increasing percentage of agar. The silicone material had higher stiffness values when compared with PAA with Al2O3. The mean Young's modulus value in cancerous tissue was 90.5 ± 4.5 kPa as compared to 93.8 ± 4.4 and 86.2 ± 4.5 kPa obtained with PAA with 2% Al2O3 phantom at a depth of 52.4 and 36.6 mm, respectively. Conclusions: PAA mixed with Al2O3 provides the most suitable tissue mimicking material for prostate cancer tumor material, while agar could form the surrounding

A rare case of unilateral discoid lupus erythematosus mimicking lupus vulgaris.

PubMed

Verma, Parul; Pathania, Sucheta; Kubba, Asha

2017-11-08

Discoidlupus erythematosus (DLE) is a chronic type of cutaneous lupus erythematosus which can present in various morphologies, and the diagnosis can be rather confounding. Prompt evaluation and treatment is necessary to prevent disfigurement and systemic involvement associated with DLE. The following case presented a diagnostic dilemma as the lesion mimicked lupus vulgaris. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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

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

Nephropathic Cystinosis Mimicking Bartter Syndrome: a Novel Mutation.

PubMed

Bastug, Funda; Nalcacioglu, Hulya; Ozaltin, Fatih; Korkmaz, Emine; Yel, Sibel

2018-01-01

Cystinosis is a rare autosomal recessive disorder resulting from defective lysosomal transport of cystine due to mutations in the cystinosin lysosomal cystine transporter (CTNS) gene. The clinical phenotype of nephropathic cystinosis is characterized by renal tubular Fanconi syndrome and development of end-stage renal disease during the first decade. Although metabolic acidosis is the classically prominent finding of the disease, a few cases may present with hypokalemic metabolic alkalosis mimicking Bartter syndrome. Bartter-like presentation may lead to delay in diagnosis and initiation of specific treatment for cystinosis. We report a case of a 6-year-old girl initially presenting with the features of Bartter syndrome that was diagnosed 2 years later with nephropathic cystinosis and a novel CTNS mutation.

Postpolypectomy Electrocoagulation Syndrome: A Mimicker of Colonic Perforation

PubMed Central

Benson, Brian C.; Myers, Jonathan J.; Laczek, Jeffrey T.

2013-01-01

Postpolypectomy electrocoagulation syndrome is a rare complication of polypectomy with electrocautery and is characterized by a transmural burn of the colon wall. Patients typically present within 12 hours after the procedure with symptoms mimicking colonic perforation. Presented is the case of a 56-year-old man who developed abdominal pain six hours after colonoscopy during which polypectomy was performed using snare cautery. CT imaging of the abdomen revealed circumferential thickening of the wall of the transverse colon without evidence of free air. The patient was treated conservatively as an outpatient and had resolution of his pain over the following four days. Recognition of the diagnosis and understanding of the treatment are important to avoid unnecessary exploratory laparotomy or hospitalization. PMID:23956889

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.

The first human case of neuroinvasive West Nile virus infection identified in Cyprus.

PubMed

Paphitou, Niki I; Tourvas, Aristomenis; Floridou, Dora; Richter, Jan; Tryfonos, Christina; Christodoulou, Christina

West Nile virus infection can pose a diagnostic challenge to clinicians, especially in geographic areas where human cases of this disease have never been encountered before. In August 2016, the first human case of West Nile virus infection was diagnosed in Cyprus. An elderly non immunosuppressed patient with a history of recent travel, presented with a clinical picture of rapidly progressing ascending paralysis mimicking Guillain-Barré syndrome. Neuroinvasive West Nile virus disease was diagnosed by detecting West Nile virus nucleic acid in the patient's cerebrospinal fluid. Public health measures were taken raising awareness regarding this disease and its prevention. Clinical vigilance to consider West Nile virus as a possible emerging pathogen in the appropriate clinical setting is warranted and could benefit individual patients. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

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

20-year Follow-up of Recurrent Glandular Odontogenic Cyst Mimicking a Periapical Lesion.

PubMed

de Freitas Silva, Brunno Santos; Yamamoto-Silva, Fernanda Paula; Sena-Filho, Marcondes; Silva Sant'Ana, Simone Sousa; Mariano-Júnior, Wilson José; de Almeida, Oslei Paes; Estrela, Carlos

2017-11-01

Periapical lesions usually are caused by root canal infection; nevertheless, other pathologies may eventually involve the tooth apex, making the correct diagnosis more difficult. Glandular odontogenic cysts (GOCs) are uncommon and, despite their cystic nature, may present an aggressive behavior and a high recurrence rate. This report describes a recurrent GOC mimicking a periapical lesion that was followed up for 20 years. A 45-year-old woman described tooth discomfort for several years in the anterior region of the mandible that was not exacerbated during eating or occlusion. Clinical examination revealed no signs of swelling, redness, or inflammation in the gingival or surrounding soft tissue. Nevertheless, periapical radiography showed a well-defined large radiolucent lesion in the periapical region of teeth #22, #23, #24, and #25. The pulp test confirmed that all these teeth were vital. An incisional biopsy was performed, and with the histopathological diagnosis of an odontogenic cyst, the lesion was enucleated surgically. After recurrence, the extensive periapical multilocular lesions were again surgically removed. Based on the microscopic findings, the final diagnosis was GOC. One year later, there were no signs of recurrence. GOCs associated with the root apex may mimic periapical inflammatory diseases. Clinical, radiographic, and histopathological findings are essential for the diagnosis of inconclusive radiolucent findings in the periapical region. Biopsy specimens should be sent to a specialized oral pathology laboratory. Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

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.

Non Lipomatous Benign Lesions Mimicking Soft-tissue Sarcomas: A Pictorial Essay

PubMed Central

CORAN, ALESSANDRO; ORSATTI, GIOVANNA; CRIMÌ, FILIPPO; RASTRELLI, MARCO; DI MAGGIO, ANTONIO; PONZONI, ALBERTO; ATTAR, SHADY; STRAMARE, ROBERTO

2018-01-01

The incidental finding of soft tissue masses is a challenge for the radiologist. Benign and malignant lesions can be differentiated relying on patient history, symptoms and mostly with the help of imaging. Ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI) become fundamental in order to distinguish these lesions but the radiologist needs to know the main characteristics of benign soft tissue masses and sarcomas. Herein, we present a pictorial review of lesions mimicking soft tissue sarcomas features. PMID:29475903

Subcutaneous Emphysema Mimicking Gas Gangrene Following Perforation of the Rectum: A Case Report

PubMed Central

Moon, Eun-Sun; Jung, Sung-Taek; Seo, Hyoung-Yeon

2004-01-01

We report a case of extensive subcutaneous emphysema of the lower extremity mimicking gas gangrene following perforation of the rectum in a 38-yr-old man. Subcutaneous emphysema of the leg may rarely occur secondary to perforation of the gastrointestinal tract and has often created serious diagnostic problems and high mortality rates. Therefore, prompt diagnosis and aggressive treatment is imperative. PMID:15483358

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.

Preventing HIV infection without targeting the virus: how reducing HIV target cells at the genital tract is a new approach to HIV prevention.

PubMed

Lajoie, Julie; Mwangi, Lucy; Fowke, Keith R

2017-09-12

For over three decades, HIV infection has had a tremendous impact on the lives of individuals and public health. Microbicides and vaccines studies have shown that immune activation at the genital tract is a risk factor for HIV infection. Furthermore, lower level of immune activation, or what we call immune quiescence, has been associated with a lower risk of HIV acquisition. This unique phenotype is observed in highly-exposed seronegative individuals from different populations including female sex workers from the Pumwani cohort in Nairobi, Kenya. Here, we review the link between immune activation and susceptibility to HIV infection. We also describe a new concept in prevention where, instead of targeting the virus, we modulate the host immune system to resist HIV infection. Mimicking the immune quiescence phenotype might become a new strategy in the toolbox of biomedical methods to prevent HIV infection. Clinical trial registration on clinicaltrial.gov: #NCT02079077.

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.

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.

[Infestation with Enterobius vermicularis mimicking appendicitis].

PubMed

Levens, Afra M A; Schurink, Maarten; Koetse, Harma A; van Baren, Robertine

2014-01-01

Gastrointestinal infestation with the parasite Enterobius vermicularis is common in humans and is usually harmless. Anal pruritus is the most characteristic symptom, but the parasites can cause severe abdominal pain mimicking appendicitis. Early recognition can prevent an unnecessary appendectomy. A six-year-old girl reported to the accident and emergency department with pain in the lower right abdominal region. She was admitted and treated for suspected perforated appendix, following physical examination supplemented with an abdominal CT scan. After antibiotic treatment the symptoms disappeared as did the abscess, apart from a minor amount of residual infiltrate. She was then readmitted twice with recurrent abdominal pain without radiological evidence of an abdominal focus. We decided to conduct a diagnostic laparoscopy and an elective appendectomy à froid. During this procedure living worms were found in the appendix. Treatment with the anthelminthicum mebendazol was effective. Gastro-intestinal infestation with E. vermicularis is very common, especially in young children. This infestation is usually harmless, but can mimic appendicitis. This infestation is easily treatable with mebendazol.

Oral desmoplastic melanoma mimicking inflammatory hyperplasia.

PubMed

Jou, Adriana; Miranda, Fábio V; Oliveira, Márcia G; Martins, Manoela D; Rados, Pantelis V; Filho, Manoel S

2012-06-01

Desmoplastic melanoma (DM) arising in the oral cavity is a rare neoplasm that may be confused with a variety of non-melanocytic benign or malignant lesions. To present a case of DM in the oral mucosa mimicking fibrous inflammatory hyperplasia, discusses the difficulties involved in the diagnosis and offers a literature review on the clinicopathologic and immunohistochemincal aspects of this neoplasm. A 62-year-old white male, smoker, was referred with a chief complaint of pain and swelling in the palate. The oral examination revealed multiple brown-to-black patches and a non-pigmented sessile nodule located on the mucosa of the hard palate. The clinical diagnosis of the pigmented lesions was either oral melanosis or melanoma. The nodular lesion was clinically diagnosed as fibrous inflammatory hyperplasia. Incisional biopsy was performed on the pigmented lesion and the microscopic sections revealed a melanotic macule. The nodular lesions histologically revealed an amelanotic desmoplastic melanoma. Reactive lesions close to a pigmented area should be investigated with great care. © 2010 The Gerodontology Society and John Wiley & Sons A/S.

Microfabricated adhesive mimicking gecko foot-hair.

PubMed

Geim, A K; Dubonos, S V; Grigorieva, I V; Novoselov, K S; Zhukov, A A; Shapoval, S Yu

2003-07-01

The amazing climbing ability of geckos has attracted the interest of philosophers and scientists alike for centuries. However, only in the past few years has progress been made in understanding the mechanism behind this ability, which relies on submicrometre keratin hairs covering the soles of geckos. Each hair produces a miniscule force approximately 10(-7) N (due to van der Waals and/or capillary interactions) but millions of hairs acting together create a formidable adhesion of approximately 10 N x cm(-2): sufficient to keep geckos firmly on their feet, even when upside down on a glass ceiling. It is very tempting to create a new type of adhesive by mimicking the gecko mechanism. Here we report on a prototype of such 'gecko tape' made by microfabrication of dense arrays of flexible plastic pillars, the geometry of which is optimized to ensure their collective adhesion. Our approach shows a way to manufacture self-cleaning, re-attachable dry adhesives, although problems related to their durability and mass production are yet to be resolved.

Microfabricated adhesive mimicking gecko foot-hair

NASA Astrophysics Data System (ADS)

Geim, A. K.; Dubonos, S. V.; Grigorieva, I. V.; Novoselov, K. S.; Zhukov, A. A.; Shapoval, S. Yu.

2003-07-01

The amazing climbing ability of geckos has attracted the interest of philosophers and scientists alike for centuries. However, only in the past few years has progress been made in understanding the mechanism behind this ability, which relies on submicrometre keratin hairs covering the soles of geckos. Each hair produces a miniscule force ~10-7 N (due to van der Waals and/or capillary interactions) but millions of hairs acting together create a formidable adhesion of ~10 N cm-2: sufficient to keep geckos firmly on their feet, even when upside down on a glass ceiling. It is very tempting to create a new type of adhesive by mimicking the gecko mechanism. Here we report on a prototype of such 'gecko tape' made by microfabrication of dense arrays of flexible plastic pillars, the geometry of which is optimized to ensure their collective adhesion. Our approach shows a way to manufacture self-cleaning, re-attachable dry adhesives, although problems related to their durability and mass production are yet to be resolved.

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

Uveal Melanoma Mimicking Advanced Coats' Disease in a Young Patient.

PubMed

Gupta, Naina; Terrell, William; Schoenfield, Lynn; Kirsch, Claudia; Cebulla, Colleen M

2016-04-01

To report a case and the unique histopathology of a necrotic uveal melanoma mimicking advanced Coats' disease in a young adult. A 26-year-old male presented with a blind, painful eye, total exudative retinal detachment, and bulbous aneurysms consistent with Coats' disease. No masses were visualized on ultrasound or CT scan, and the patient underwent enucleation of the eye. Histopathology of the involved eye confirmed a necrotic uveal melanoma with persistent spindle cells forming a collar around residual tumor vessels. Careful consideration is needed in approaching any patient with a blind, painful eye and opaque media, even in younger populations.

Granulomatous mastitis caused by histoplasma and mimicking inflammatory breast carcinoma.

PubMed

Osborne, B M

1989-01-01

Two cases of a lobular, necrotizing granulomatous process causing a unilateral painful breast mass mimicking carcinoma are presented for comparison. While the morphologic appearance in each case was that of lobular granulomatous mastitis, the etiologic agent in one case appeared to be Histoplasma capsulatum, based on Grocott methenamine silver staining, and represents the second reported case of histoplasmosis involving only breast parenchyma. Awareness of the rare entity, granulomatous mastitis, is important for the pathologist because the definitive diagnosis is made microscopically. Thorough evaluation of the breast tissue is essential for its management and should eventually contribute to the clarification of its etiology.

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.

Rheumatic mitral valve stenosis mimicking advanced lung cancer.

PubMed

von Lueder, Thomas; Steine, Kjetil; Nerdrum, Tone; Steen, Torkel; Bay, Dag; Humerfelt, Sjur; Atar, Dan

2007-09-01

This report describes a patient with a perihilar mass and mediastinal lymphadenopathy mimicking advanced lung cancer. The patient, a 45-year old regular smoker, was admitted to hospital for dyspnea and tachyarrhythmia, and during hospitalization he was diagnosed with severe rheumatic mitral valve stenosis (MVS) and aortic regurgitation as well as pulmonary venous hypertension. Surgical valve replacement and removal of an atrial thrombus was delayed considerably by diagnostic work-up for suspected malignancy. After cardiac surgery had been performed, recovery was uneventful. On follow-up 1 year later, echocardiography showed well-functioning prosthetic mitral and aortic valves, and normal findings on chest X-ray. Perihilar masses and mediastinal lymphadenopathy presented in this case constitute infrequent yet established findings in MVS, resulting from pulmonary venous congestion and hypertension, and focal lymphedema.

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

A Hepatocyte-Mimicking Antidote for Alcohol Intoxication.

PubMed

Xu, Duo; Han, Hui; He, Yuxin; Lee, Harrison; Wu, Di; Liu, Fang; Liu, Xiangsheng; Liu, Yang; Lu, Yunfeng; Ji, Cheng

2018-04-11

Alcohol intoxication causes serious diseases, whereas current treatments are mostly supportive and unable to remove alcohol efficiently. Upon alcohol consumption, alcohol is sequentially oxidized to acetaldehyde and acetate by the endogenous alcohol dehydrogenase and aldehyde dehydrogenase, respectively. Inspired by the metabolism of alcohol, a hepatocyte-mimicking antidote for alcohol intoxication through the codelivery of the nanocapsules of alcohol oxidase (AOx), catalase (CAT), and aldehyde dehydrogenase (ALDH) to the liver, where AOx and CAT catalyze the oxidation of alcohol to acetaldehyde, while ALDH catalyzes the oxidation of acetaldehyde to acetate. Administered to alcohol-intoxicated mice, the antidote rapidly accumulates in the liver and enables a significant reduction of the blood alcohol concentration. Moreover, blood acetaldehyde concentration is maintained at an extremely low level, significantly contributing to liver protection. Such an antidote, which can eliminate alcohol and acetaldehyde simultaneously, holds great promise for the treatment of alcohol intoxication and poisoning and can provide therapeutic benefits. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Domino model for geomagnetic field reversals.

PubMed

Mori, N; Schmitt, D; Wicht, J; Ferriz-Mas, A; Mouri, H; Nakamichi, A; Morikawa, M

2013-01-01

We solve the equations of motion of a one-dimensional planar Heisenberg (or Vaks-Larkin) model consisting of a system of interacting macrospins aligned along a ring. Each spin has unit length and is described by its angle with respect to the rotational axis. The orientation of the spins can vary in time due to spin-spin interaction and random forcing. We statistically describe the behavior of the sum of all spins for different parameters. The term "domino model" in the title refers to the interaction among the spins. We compare the model results with geomagnetic field reversals and dynamo simulations and find strikingly similar behavior. The aggregate of all spins keeps the same direction for a long time and, once in a while, begins flipping to change the orientation by almost 180 degrees (mimicking a geomagnetic reversal) or to move back to the original direction (mimicking an excursion). Most of the time the spins are aligned or antialigned and deviate only slightly with respect to the rotational axis (mimicking the secular variation of the geomagnetic pole with respect to the geographic pole). Reversals are fast compared to the times in between and they occur at random times, both in the model and in the case of the Earth's magnetic field.

Hepatitis Virus Infections in Poultry.

PubMed

Yugo, Danielle M; Hauck, Ruediger; Shivaprasad, H L; Meng, Xiang-Jin

2016-09-01

Viral hepatitis in poultry is a complex disease syndrome caused by several viruses belonging to different families including avian hepatitis E virus (HEV), duck hepatitis B virus (DHBV), duck hepatitis A virus (DHAV-1, -2, -3), duck hepatitis virus Types 2 and 3, fowl adenoviruses (FAdV), and turkey hepatitis virus (THV). While these hepatitis viruses share the same target organ, the liver, they each possess unique clinical and biological features. In this article, we aim to review the common and unique features of major poultry hepatitis viruses in an effort to identify the knowledge gaps and aid the prevention and control of poultry viral hepatitis. Avian HEV is an Orthohepevirus B in the family Hepeviridae that naturally infects chickens and consists of three distinct genotypes worldwide. Avian HEV is associated with hepatitis-splenomegaly syndrome or big liver and spleen disease in chickens, although the majority of the infected birds are subclinical. Avihepadnaviruses in the family of Hepadnaviridae have been isolated from ducks, snow geese, white storks, grey herons, cranes, and parrots. DHBV evolved with the host as a noncytopathic form without clinical signs and rarely progressed to chronicity. The outcome for DHBV infection varies by the host's ability to elicit an immune response and is dose and age dependent in ducks, thus mimicking the pathogenesis of human hepatitis B virus (HBV) infections and providing an excellent animal model for human HBV. DHAV is a picornavirus that causes a highly contagious virus infection in ducks with up to 100% flock mortality in ducklings under 6 wk of age, while older birds remain unaffected. The high morbidity and mortality has an economic impact on intensive duck production farming. Duck hepatitis virus Types 2 and 3 are astroviruses in the family of Astroviridae with similarity phylogenetically to turkey astroviruses, implicating the potential for cross-species infections between strains. Duck astrovirus (DAstV) causes

Clinical and pathologic changes in a guinea pig aerosol challenge model of acute Q fever.

PubMed

Russell-Lodrigue, K E; Zhang, G Q; McMurray, D N; Samuel, J E

2006-11-01

Acute Q fever is a zoonotic disease caused by the obligate intracellular bacterium Coxiella burnetii and can manifest as a flu-like illness, pneumonia, or hepatitis. A need exists in Q fever research for animal models mimicking both the typical route of infection (inhalation) and the clinical illness seen in human cases of Q fever. A guinea pig aerosol challenge model was developed using C. burnetii Nine Mile phase I (RSA 493), administered using a specialized chamber designed to deliver droplet nuclei directly to the alveolar spaces. Guinea pigs were given 10(1) to 10(6) organisms and evaluated for 28 days postinfection. Clinical signs included fever, weight loss, respiratory difficulty, and death, with the degree and duration of response corresponding to the dose of organism delivered. Histopathologic evaluation of the lungs of animals infected with a high dose showed coalescing panleukocytic bronchointerstitial pneumonia at 7 days postinfection that resolved to multifocal lymphohistiocytic interstitial pneumonia by 28 days. Guinea pigs receiving a killed whole-cell vaccine prior to challenge with the highest dose of C. burnetii were protected against lethal infection and did not develop fever. Clinical signs and pathological changes noted for these guinea pigs were comparable to those seen in human acute Q fever, making this an accurate and valuable animal model of human disease.

Non Lipomatous Benign Lesions Mimicking Soft-tissue Sarcomas: A Pictorial Essay.

PubMed

Coran, Alessandro; Orsatti, Giovanna; Crimì, Filippo; Rastrelli, Marco; DI Maggio, Antonio; Ponzoni, Alberto; Attar, Shady; Stramare, Roberto

2018-01-01

The incidental finding of soft tissue masses is a challenge for the radiologist. Benign and malignant lesions can be differentiated relying on patient history, symptoms and mostly with the help of imaging. Ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI) become fundamental in order to distinguish these lesions but the radiologist needs to know the main characteristics of benign soft tissue masses and sarcomas. Herein, we present a pictorial review of lesions mimicking soft tissue sarcomas features. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

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.