Author: Rodondi, Nicolas ; Ortega, Natalia ; Schütte, Leona ; von Gunten, Armin ; de Crom, Tosca O.E. ; Chocano-Bedoya, Patricia O. ; Vinceti, Marco ; Voortman, Trudy ; de Crom, Tosca O E ; Marques-Vidal, Pedro ; Chocano-Bedoya, Patricia O ; Okereke, Olivia I. ; Okereke, Olivia I ; Chiolero, Arnaud

BACKGROUNDTargeting effective strategies to prevent cognitive decline is key in the aging population. Some diets have been linked to a slower cognitive decline, potentially through reducing inflammation. We aimed at determining the effect of inflammatory dietary patterns (IDPs) on cognitive function in three population-based cohorts.METHODSIn this longitudinal study, we analyzed data from the Canadian Longitudinal Study of Aging, CoLaus|PsyCoLaus and Rotterdam Study. Our analytical sample included participants over 55 years old with baseline data on cognition, dietary intake, and inflammatory markers. IDPs were derived for each cohort using reduced rank regression to reflect maximal variation in three inflammatory markers. We calculated scores of consumption of the IDPs, higher scores indicating more IDP consumption. We used inverse probability of treatment and censoring weights in the marginal structural models to estimate associations of higher versus lower quarters of consumption of an IDP on general cognition (Mini-Mental State Evaluation) and four cognitive domains (memory, verbal fluency, verbal learning and processing speed and executive function) during at least 3 years of follow-up.RESULTSWe included 10,366 participants (mean age 68) followed-up for a mean of 5 years. Diet explained between 1 and 2% of the variation of the inflammatory markers. There were no differences in general cognition when comparing the highest to the lowest quarter of consumption of IDPs among the three cohorts. Mean differences for the four cognitive domains were of small magnitude across cohorts and not clinically relevant.CONCLUSIONDiet explained low variation in inflammatory markers. Consuming IDPs was not associated with mean differences in general or domain-specific cognitive function.

01 Jul 2024·Heliyon

Promising brain biodistribution of insulin via intranasal dry powder for nose-to-brain delivery

Article

Author: Hayun ; Muntu, Cynthia Marisca ; Surini, Silvia ; Avanti, Christina

Nose-to-brain delivery (NTBD) offering potential benefits for treating Alzheimer's disease. In previous research, insulin dry powder (IDP) formulation for NTBD was developed, exhibiting favorable stability. This study aims to conduct in vitro and ex vivo assessment of release, permeation, mucoadhesion and histopathology, as well as an in vivo biodistribution study to produce IDP for NTBD and evaluate brain biodistribution. Spray-freeze-dried IDP formulations with varying weight ratios of trehalose-to-inulin were produced and analyzed. The release study was carried out in PBS with a pH of 5.8 stirred at 50 rpm and maintained at 37 °C ± 0.5 °C. Goat nasal mucosa was used for ex vivo permeation and mucoadhesion testing under similar conditions. An ex vivo histopathological examination and an in vivo study using enzyme-linked immunosorbent assay, were also performed. The IDP dissolution study demonstrated complete release of all IDPs within 120 min. The permeation study indicated that steady-state conditions were observed between 30 and 240 min. The mucoadhesion study unveiled that IDP F5 exhibited the fastest mucoadhesion time and the least force required within the fastest time of 43.60 ± 2.57 s. The histopathological study confirmed that none of the tested IDPs induced irritation in the nasal mucosa. Furthermore, the biodistribution study demonstrated the absence of detectable insulin in the plasma, while IDP F3 exhibited the highest deposited concentration of insulin within both the olfactory bulb and the whole brain. The extensive evaluation of the IDP formulations through in vitro, ex vivo, and in vivo studies implies their strength non-invasive NTBD. IDP F3, with a 1:1 wt ratio of trehalose to inulin, exhibited favorable brain biodistribution outcomes and was recommended for further investigation and development in the context of NTBD.

01 Jan 2023·The Journal of the American Dental Association

Quantifying the risk of prosthetic joint infections after invasive dental procedures and the effect of antibiotic prophylaxis

Article

Author: Bloemers, Sarah ; Rosario, Bedda L. ; Pack, Cory ; Lockhart, Peter B. ; Gibson, Teresa B. ; Thornhill, Martin H. ; Springer, Bryan ; Baddour, Larry M.

BACKGROUNDDentists face the expectations of orthopedic surgeons and patients with prosthetic joints to provide antibiotic prophylaxis (AP) before invasive dental procedures (IDPs) to reduce the risk of late periprosthetic joint infections (LPJIs), despite the lack of evidence associating IDPs with LPJIs, lack of evidence of AP efficacy, risk of AP-related adverse reactions, and potential for promoting antibiotic resistance. The authors aimed to identify any association between IDPs and LPJIs and whether AP reduces LPJI incidence after IDPs.METHODThe authors performed a case-crossover analysis comparing IDP incidence in the 3 months immediately before LPJI hospital admission (case period) with the preceding 12-month control period for all LPJI hospital admissions with commercial or Medicare supplemental or Medicaid health care coverage and linked dental and prescription benefits data.RESULTSOverall, 2,344 LPJI hospital admissions with dental and prescription records (n = 1,160 commercial or Medicare supplemental and n = 1,184 Medicaid) were identified. Patients underwent 4,614 dental procedures in the 15 months before LPJI admission, including 1,821 IDPs (of which 18.3% had AP). Our analysis identified no significant positive association between IDPs and subsequent development of LPJIs and no significant effect of AP in reducing LPJIs.CONCLUSIONSThe authors identified no significant association between IDPs and LPJIs and no effect of AP cover of IDPs in reducing the risk of LPJIs.PRACTICAL IMPLICATIONSIn the absence of benefit, the continued use of AP poses an unnecessary risk to patients from adverse drug reactions and to society from the potential of AP to promote development of antibiotic resistance. Dental AP use to prevent LPJIs should, therefore, cease.

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Indication	Highest Phase	Country/Location	Organization	Date
Graft Rejection	Preclinical	US	Hollis Eden Pharmaceuticals	-

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