Faculty Bibliography

INTRODUCTION/BACKGROUND:Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in infants and elderly and to date, there is no safe or effective vaccine against RSV. Areas Covered: This review provides a roadmap to RSV vaccine development. It is a journey spanning over more than half a century from the initial disappointment with inactivated formalin vaccine to the current advancements in vaccine technology. We highlight the important aspects of RSV structural biology and protective immune response. We include discussion of newer fusion glycoprotein immune targets and current vaccine candidates. We used Pub Med and Medline resources for literature search. Expert opinion: A resurgence of information on the burden related to RSV infection coupled with the newer understanding of the molecular mechanism of RSV infection has reignited a tremendous activity in RSV vaccine discovery. The vaccine pipeline is diverse and target populations are varied, thus making the goal of a safe and effective RSV vaccine in the future within reach.

Age-associated deposition of amyloid-β in cerebral blood vessels, a condition referred to as cerebral amyloid angiopathy, can contribute to stroke and dementia. This research aimed to design new radioactive technetium-99 m complexes that bind to amyloid-β plaques that have the potential to assist in diagnosis of cerebral amyloid angiopathy using single-photon-emitted computed tomography (SPECT) imaging. Six new pyridylthiosemicarbazide ligands containing either benzofuran or styrylpyridyl functional groups that are known to selectively bind to amyloid plaques were prepared. Non-radioactive isotopes of technetium are not available so rhenium was used as a surrogate for exploratory chemistry. The new ligands were used to prepare well-defined [Re-oxo]³⁺ complexes where two pyridylthiosemicarbazide ligands were coordinated to a single metal ion to give bivalent complexes with two amyloid-β targeting functional groups. The interaction of the [Re-oxo]³⁺ complexes with synthetic amyloid-β_1-42 and with amyloid plaques in human brain tissue was investigated. Two ligands were selected to develop methods to prepare their [^99mTc-oxo]³⁺ complexes at the tracer level. These technetium-99 m complexes are likely to be isostructural to their rhenium-oxo analogues.

Clostridium difficile is an important cause of health care associated infections. The epidemiology of C. difficile infection (CDI) in children has changed over the past few decades. There is now a higher incidence in hospitalized children, and there has been an emergence of community-onset infection. A hypervirulent strain, North American pulse type 1, has also developed. Neonates and young infants have high rates of colonization but rarely have symptoms. The well-known risk factor for CDI in children age 2 years or older is antibiotic use. Inflammatory bowel disease and cancer are associated with increased incidence and severity of CDI. Nucleic acid amplification tests are now widely used for diagnosis given their rapid turnover and higher sensitivity and specificity. The treatment for an initial episode and first recurrence is oral metronidazole. Oral vancomycin is reserved for second recurrence or severe cases. A new treatment option, fecal bowel transplant, has been reported to be safe and effective in adults, and studies are now being conducted in children. [Pediatr Ann. 2018;47(9):e359-e365.].

Infection-related glomerulonephritis results from glomerular immune complex deposition due to a variety of potential pathogens. Poststreptococcal glomerulonephritis is the best known example. We present a case of acute infection-related glomerulonephritis associated with disseminated gonococcal infection in a sexually active 13-year-old girl, the first report of such an association in the absence of endocarditis. The patient presented with features of acute disseminated gonococcal infection including fever, hypotension, tenosynovitis, polyarthralgias and petechiae. She developed hypocomplementemic glomerulonephritis synchronous with the acute infection. The renal biopsy revealed a diffuse endocapillary proliferative and exudative glomerulonephritis with subepithelial electron-dense humps and granular glomerular capillary wall staining for C3 and IgG, typical of acute postinfectious glomerulonephritis. After treatment and resolution of the gonococcal infection, the serum creatinine, complement levels and urine sediment normalised. The only residual renal damage 16 months later was low-grade proteinuria.

Bis(thiosemicarbazonato)copper(II) complexes are of interest as potential therapeutics for cancer and neurodegenerative diseases as well as imaging agents for positron emission tomography (PET). The cellular uptake of six bis(thiosemcarbazonato)copper(II)complexes derived from glyoxal, with different functional groups Cu(gtsx) where x = different functional groups, was investigated in SKOV-3, HEK293, and HEK293 P-gp cell lines. Treatment of the cells with the copper complexes increased intracellular copper and increased levels of p-ERK due to activation of the Ras-Raf-MEK-ERK pathway. Treatment of SKOV-3 cells with low concentrations (μM) of two of the copper complexes led to trafficking of the endogenous copper transporter ATP7A from the Golgi network to the cell membrane. Experiments in HEK293 and HEK293-P-gp cells suggest that Cu(gtsm) and Cu(gtse) are substrates for the P-gp efflux protein but the complex with a pyrrolidine functional group, Cu(gtspyr), is not. A PET experiment in mice showed that [⁶⁴Cu]Cu(gtspyr) has reasonable brain uptake but high liver uptake.