Novel Approach for Evaluation of Bacteroides fragilis Protective Role against Bartonella henselae Liver Damage in Immunocompromised Murine Model

Bartonella henselae is a gram-negative facultative intracellular bacterium and is the causative agent of cat-scratch disease. Our previous data have established that Bacteroides fragilis colonization is able to prevent B. henselae damages through the polysaccharide A (PSA) in an experimental murine model. In order to determine whether the PSA is essential for the protection against pathogenic effects of B. henselae in immunocompromised hosts, SCID mice were co-infected with B. fragilis wild type or its mutant B. fragilis 1PSA and the effects of infection on murine tissues have been observed by High-Frequency Ultrasound (HFUS), histopathological examination, and Transmission Electron Microscopy (TEM). For the first time, echostructure, hepatic lobes length, vascular alterations, and indirect signs of hepatic dysfunctions, routinely used as signs of disease in humans, have been analyzed in an immunocompromised murine model. Our findings showed echostructural alterations in all infected mice compared with the Phosphate Buffer Solution (PBS) control group; further, those infected with B. henselae and co-infected with B. henselae/B. fragilis 1PSA presented the major echostructural alterations. Half of the mice infected with B. henselae and all those co-infected with B. henselae/B. fragilis 1PSA have showed an altered hepatic echogenicity compared with the renal cortex. The echogenicity score of co-infected mice with B. henselae/B. fragilis 1PSA differed significantly compared with the PBS control group (p < 0.05). Moreover the inflammation score of the histopathological evaluation was fairly concordant with ultrasound findings. Ultrastructural analysis performed by TEM revealed no significant alterations in liver samples of SCID mice infected with B. fragilis wild type while those infected with B. fragilis 1PSA showed the presence of collagen around the main vessels compared with the PBS control group. The liver samples of mice infected with B. henselae showed macro-areas rich in collagen, stellate cells, and histiocytic cells. Interestingly, our data demonstrated that immunocompromised SCID mice infected with B. henselaeand co-infected with B. henselae/B. fragilis ΔPSA showed the most severe morpho-structural liver damage. In addition, these results suggests that the HFUS together with histopathological evaluation could be considered good imaging approach to evaluate hepatic alterations

Mouse models of neurodegenerative disease: preclinical imaging and neurovascular component.

Neurodegenerative diseases represent great challenges for basic science and clinical medicine because of their prevalence, pathologies, lack of mechanism-based treatments, and impacts on individuals. Translational research might contribute to the study of neurodegenerative diseases. The mouse has become a key model for studying disease mechanisms that might recapitulate in part some aspects of the corresponding human diseases. Neurode- generative disorders are very complicated and multifacto- rial. This has to be taken in account when testing drugs. Most of the drugs screening in mice are very di cult to be interpretated and often useless. Mouse models could be condiderated a ‘pathway models’, rather than as models for the whole complicated construct that makes a human disease. Non-invasive in vivo imaging in mice has gained increasing interest in preclinical research in the last years thanks to the availability of high-resolution single-photon emission computed tomography (SPECT), positron emission tomography (PET), high eld Magnetic resonance, Optical Imaging scanners and of highly speci c contrast agents. Behavioral test are useful tool to characterize di erent ani- mal models of neurodegenerative pathology. Furthermore, many authors have observed vascular pathological features associated to the di erent neurodegenerative disorders. Aim of this review is to focus on the di erent existing animal models of neurodegenerative disorders, describe behavioral tests and preclinical imaging techniques used for diagnose and describe the vascular pathological features associated to these diseases

Mental health challenges and digital platform opportunities in patients and families affected by pediatric neuromuscular diseases - experiences from Switzerland

Receiving the diagnosis of a severe disease may present a traumatic event for patients and their families. To cope with the related challenges, digital interventions can be combined with traditional psychological support to help meet respective needs. We aimed to 1) discuss the most common consequences and challenges for resilience in Neuro Muscular Disease patients and family members and 2) elicit practical needs, concerns, and opportunities for digital platform use. We draw from findings of a transdisciplinary workshop and conference with participants ranging from the fields of clinical practice to patient representatives. Reported consequences of the severe diseases were related to psychosocial challenges, living in the nexus between physical development and disease progression, social exclusion, care-related challenges, structural and financial challenges, and non-inclusive urban design. Practical needs and concerns regarding digital platform use included social and professional support through these platforms, credibility and trust in online information, and concerns about privacy and informed consent. Furthermore, the need for safe, reliable, and expert-guided information on digital platforms and psychosocial and relationship-based digital interventions was expressed. There is a need to focus on a family-centered approach in digital health and social care and a further need in researching the suitability of digital platforms to promote resilience in the affected population. Our results can also inform city councils regarding investments in inclusive urban design allowing for disability affected groups to enjoy a better quality of life

New CXCR4 Antagonist Peptide R (Pep R) Improves Standard Therapy in Colorectal Cancer

he chemokine receptor CXCR4 is overexpressed and functional in colorectal cancer. To investigate the role of CXCR4 antagonism in potentiating colon cancer standard therapy, the new peptide CXCR4 antagonist Peptide R (Pep R) was employed. Human colon cancer HCT116 xenograft-bearing mice were treated with chemotherapeutic agents (CT) 5-Fluorouracil (5FU) and oxaliplatin (OX) or 5FU and radio chemotherapy (RT-CT) in the presence of Pep R. After two weeks, CT plus Pep R reduced by 4-fold the relative tumor volume (RTV) as compared to 2- and 1.6-fold reductions induced, respectively, by CT and Pep R. In vitro Pep R addition to CT/RT-CT impaired HCT116 cell growth and further reduced HCT116 and HT29 clonal capability. Thus, the hypothesis that Pep R could target the epithelial mesenchyme transition (EMT) process was evaluated. While CT decreased ECAD and increased ZEB-1 and CD90 expression, the addition of Pep R restored the pretreatment expression. In HCT116 and HT29 cells, CT/RT-CT induced a population of CD133+CXCR4+ cells, supposedly a stem-resistant cancer cell population, while Pep R reduced it. Taken together, the results showed that targeting CXCR4 ameliorates the effect of treatment in colon cancer through inhibition of cell growth and reversal of EMT treatment-induced markers, supporting further clinical studies

Mental health challenges and digital platform opportunities in patients and families affected by pediatric neuromuscular diseases : experiences from Switzerland

Receiving the diagnosis of a severe disease may present a traumatic event for patients and their families. To cope with the related challenges, digital interventions can be combined with traditional psychological support to help meet respective needs. We aimed to 1) discuss the most common consequences and challenges for resilience in Neuro Muscular Disease patients and family members and 2) elicit practical needs, concerns, and opportunities for digital platform use. We draw from findings of a transdisciplinary workshop and conference with participants ranging from the fields of clinical practice to patient representatives. Reported consequences of the severe diseases were related to psychosocial challenges, living in the nexus between physical development and disease progression, social exclusion, care-related challenges, structural and financial challenges, and non-inclusive urban design. Practical needs and concerns regarding digital platform use included social and professional support through these platforms, credibility and trust in online information, and concerns about privacy and informed consent. Furthermore, the need for safe, reliable, and expert-guided information on digital platforms and psychosocial and relationship-based digital interventions was expressed. There is a need to focus on a family-centered approach in digital health and social care and a further need in researching the suitability of digital platforms to promote resilience in the affected population. Our results can also inform city councils regarding investments in inclusive urban design allowing for disability affected groups to enjoy a better quality of life

Detección y aislamiento de Escherichia coli productora de toxina Shiga y conteo de poblaciones microbianas en carne bovina Kosher argentina para exportar a Israel

The aim of this study was to provide data on the frequency of Top 7 Shiga toxin-producing Escherichia coli (STEC) and microbial population counts on processed beef from Argentinean Kosher cattle abattoirs authorized to export to Israel. A total of 480 samples (forequarters, primal cuts, trimmings) were taken and analyzed for Top 7 STEC detection and isolation and for mesophilic aerobic organism, coliform and E. coli enumeration. Differences in stx detection and microbial population counts on forequarter samples before and after salting were not statistically significant (P &gt;0.05). All samples were negative for Top 7 STEC. Differences were significant for all microbial counts in primal cuts (P &lt;0.001). Neck samples showed a higher level of contamination with the three groups of microorganisms than fore shank and brisket samples. The prevalence of stx was lower than that reported worldwide and in Argentinean export abattoirs. Salting did not significantly reduce the microbial load on forequarters.El objetivo de este estudio fue determinar la frecuencia de Escherichia coli productora de toxina Shiga (STEC) Top 7 y realizar recuentos de poblaciones microbianas en carne Kosher de frigoríficos argentinos autorizados para exportar a Israel. Se tomaron 480 muestras (cuartos delanteros, cortes y recortes) y se realizó la detección y aislamiento de STEC Top 7 y el recuento de microorganismos aerobios mesófilos, coliformes y Escherichia coli. No se identificaron diferencias estadísticamente significativas (P &gt;0,05) en la detección de stx y en los recuentos de poblaciones microbianas en las muestras de cuartos delanteros antes y después del salado. Todas las muestras fueron negativas para STEC Top 7. Se hallaron diferencias estadísticamente significativas (P &lt;0,001) en todos los recuentos de poblaciones microbianas de los cortes. Las muestras de cogote tuvieron recuentos de poblaciones microbianas mayores a los de las muestras de brazuelo y pecho. La prevalencia de stx obtenida en el presente estudio fue menor a las reportadas en el resto del mundo y en frigoríficos exportadores de Argentina. El salado no redujo significativamente la carga microbiana de los cuartos delanteros bovinos

State-of-the-Art Preclinical Photoacoustic Imaging in Oncology: Recent Advances in Cancer Theranostics

The optical imaging plays an increasing role in preclinical studies, particularly in cancer biology. The combined ultrasound and optical imaging, named photoacoustic imaging (PAI), is an emerging hybrid technique for real-time molecular imaging in preclinical research and recently expanding into clinical setting. PAI can be performed using endogenous contrast, particularly from oxygenated and deoxygenated hemoglobin and melanin, or exogenous contrast agents, sometimes targeted for specific biomarkers, providing comprehensive morphofunctional and molecular information on tumor microenvironment. Overall, PAI has revealed notable opportunities to improve knowledge on tumor pathophysiology and on the biological mechanisms underlying therapy. The aim of this review is to introduce the principles of PAI and to provide a brief overview of current PAI applications in preclinical research, highlighting also on recent advances in clinical translation for cancer diagnosis, staging, and therapy.</jats:p