The Silent Threat: Bartonella quintana Endocarditis Unveiling Heart Failure and Severe Pulmonary Hypertension.

BACKGROUND Bartonella quintana is a slow-growing gram-negative bacterium that can cause severe culture-negative endocarditis. In many cases, its insidious onset can be difficult to diagnose given the variable symptoms in the early phases of the disease. This delay in detection and thus treatment can cause advanced consequences of the disease, including heart failure and severe pulmonary hypertension. CASE REPORT A 51-year-old man presented to the Emergency Department with signs and symptoms indicating an acute stroke. Further investigation showed that the source was cardioembolic, and despite negative blood cultures, endocarditis was suspected due to echocardiogram findings. Bartonella endocarditis was diagnosed based on serology results. Further testing indicated severe pulmonary hypertension, a sequelae of chronic heart failure in the setting of endocarditis. This caused a significant delay in valvular repair surgery. This case illustrates the progression from acute to chronic infection, the sequelae of this disease process, and the considerations involved in management. CONCLUSIONS Bartonella is an under-appreciated cause of endocarditis and can evolve into chronic disease with clinical consequences requiring nuanced management. We described a case of chronic culture-negative endocarditis that presented with acute embolic stroke and the sequelae of severe multi-valvular disease in a patient with recent incarceration and unstable housing. This case provides clinicians with valuable insight into the recognition of Bartonella endocarditis, the variable clinical presentations of this pathology, the nuanced and multifactorial approaches to medical management, and the indications for surgery.

A farnesyltransferase inhibitor activates lysosomes and reduces tau pathology in mice with tauopathy.

Tau inclusions are a shared feature of many neurodegenerative diseases, among them frontotemporal dementia caused by tau mutations. Treatment approaches for these conditions include targeting posttranslational modifications of tau proteins, maintaining a steady-state amount of tau, and preventing its tendency to aggregate. We discovered a new regulatory pathway for tau degradation that operates through the farnesylated protein, Rhes, a GTPase in the Ras family. Here, we show that treatment with the farnesyltransferase inhibitor lonafarnib reduced Rhes and decreased brain atrophy, tau inclusions, tau sumoylation, and tau ubiquitination in the rTg4510 mouse model of tauopathy. In addition, lonafarnib treatment attenuated behavioral abnormalities in rTg4510 mice and reduced microgliosis in mouse brain. Direct reduction of Rhes in the rTg4510 mouse by siRNA reproduced the results observed with lonafarnib treatment. The mechanism of lonafarnib action mediated by Rhes to reduce tau pathology was shown to operate through activation of lysosomes. We finally showed in mouse brain and in human induced pluripotent stem cell-derived neurons a normal developmental increase in Rhes that was initially suppressed by tau mutations. The known safety of lonafarnib revealed in human clinical trials for cancer suggests that this drug could be repurposed for treating tauopathies.

Cell-mediated remodeling of biomimetic encapsulating hydrogels triggered by adipogenic differentiation of adipose stem cells.

One of the most common regenerative therapies is autologous fat grafting, which frequently suffers from unexpected volume loss. One approach is to deliver adipose stem cells encapsulated in the engineered hydrogels supportive of cell survival, differentiation, and integration after transplant. We describe an encapsulating, biomimetic poly(ethylene)-glycol hydrogel, with embedded peptides for attachment and biodegradation. Poly(ethylene)-glycol hydrogels containing an Arg-Gly-Asp attachment sequence and a matrix metalloprotease 3/10 cleavage site supported adipose stem cell survival and showed remodeling initiated by adipogenic differentiation. Arg-Gly-Asp-matrix metalloprotease 3/10 cleavage site hydrogels showed an increased number and area of lacunae or holes after adipose stem cell differentiation. Image analysis of adipose stem cells in Arg-Gly-Asp-matrix metalloprotease 3/10 cleavage site hydrogels showed larger Voronoi domains, while cell density remained unchanged. The differentiated adipocytes residing within these newly remodeled spaces express proteins and messenger RNAs indicative of adipocytic differentiation. These engineered scaffolds may provide niches for stem cell differentiation and could prove useful in soft tissue regeneration.

'Abnormal' cervical imaging?: Cervical pneumatocysts - A case report of a cervical spine pneumatocyst.

To our knowledge there are only 15 reported cases of pneumatocysts in the cervical spine, but awareness of their existence should help the clinician when diagnosing abnormalities in radiological images. When faced with intravertebral gas, in addition to considering more sinister causes, one should consider the differentials including pneumatocysts. Despite our relative lack of understanding of these benign lesions the knowledge that they can change over time should prevent unnecessary testing or treating. We present a patient who fell down stairs and was found to have cervical intravertebral gas, on computed tomography imaging, with the typical appearance of a pneumatocyst.