Antiretroviral therapy (ART) has changed the outcome of human immunodeficiency virus type one (HIV-1) infection from certain death to a life free of disease co-morbidities. However, infected people must remain on life-long daily ART. ART reduces but fails to eliminate the viral reservoir. In order to improve upon current treatment regimens, our laboratory created long acting slow effective release (LASER) ART nanoformulated prodrugs from native medicines. LASER ART enables antiretroviral drugs (ARVs) to better reach target sites of HIV-1 infection while, at the same time, improve ART's half-life and potency. However, novel ARV design has been slowed by prolonged pharmacokinetic testing requirements. To such ends, tri-modal theranostic nanoparticles were created with single-photon emission computed tomography (SPECT/CT), magnetic resonance imaging (MRI) and fluorescence capabilities to predict LASER ART biodistribution. The created theranostic ARV probes were then employed to monitor drug tissue distribution and potency. Intrinsically Indium (In) radiolabeled, europium doped cobalt-ferrite particles and rilpivirine were encased in a polycaprolactone core surrounded by a lipid shell (InEuCF-RPV). Particle cell and tissue distribution, and antiretroviral activities were sustained in macrophage tissue depots. InEuCF-PCL/RPV particles injected into mice demonstrated co-registration of MRI and SPECT/CT tissue signals with RPV and cobalt. Cell and animal particle biodistribution paralleled ARV activities. We posit that particle selection can predict RPV distribution and potency facilitated by multifunctional theranostic nanoparticles.

Background Disseminated Clostridium septicum infection is an uncommon complication associated with malignancies, particular colonic adenocarcinoma. The organism appears to preferentially colonize large masses in rare individuals and subsequently seed the blood via mucosal ulceration. This has rarely been reported to lead to central nervous system infection and, in several cases, rapidly progressive pneumocephalus. In the few cases reported, this was a universally fatal condition. The current case adds to the reports of this extremely rare complication and provides a unique and complete clinicopathologic characterization with autopsy examination, microscopy, and molecular testing. Case Presentation A 60-year-old man with no known past medical history was discovered having seizure-like activity and stroke-like symptoms. Blood cultures turned positive after six hours. Imaging revealed a large, irregular cecal mass as well as 1.4 cm collection of air in the left parietal lobe that progressed to over 7 cm within 8 h. By the following morning, the patient had lost all neurologic reflexes and died. Post-mortem examination revealed brain tissue with multiple grossly evident cystic spaces and intraparenchymal hemorrhage, while microscopic exam showed diffuse hypoxic-ischemic injury and gram-positive rods. Clostridium septicum was identified on blood cultures and was confirmed in paraffin embedded tissue from the brain by 16 S ribosomal sequencing and from the colon by C. septicum specific PCR. Conclusions C. septicum is an anaerobic, gram-positive rod that can become invasive and is strongly associated with gastrointestinal pathology including colonic adenocarcinomas. Central nervous system infection with rapidly progressive pneumocephalus is a rarely reported and universally fatal complication of disseminated C. septicum infection.

Background. Pulmonary alveolar microlithiasis (PAM) is a rare lung disease characterized by the deposition of calcium phosphate microliths or calcospherites, within the alveolar airspace. Typical imaging findings demonstrate a “sandstorm” appearance due to bilateral, interstitial sand-like micronodularities with basal predominance. Methods and Results. We describe an unusual case of a 48-year-old male with severe, familial PAM ultimately treated with a bilateral lung transplant. Conclusions. PAM is a rare lung disease caused by a mutation in the SLC34A2 gene, which encodes for a sodium-phosphate cotransporter in type II alveolar cells, leading to accumulation of intra-alveolar phosphate causing microlith formation. PAM has an indolent course but can progress to chronic hypoxic respiratory failure, ultimately requiring lung transplant, the only known effective treatment.