Publications by authors named "Luigi Fontana"

194 Publications

Effects of dietary restriction on neuroinflammation in neurodegenerative diseases.

J Exp Med 2021 Feb;218(2)

Department of Neurology, Washington University in St. Louis, St. Louis, MO.

Recent and accumulating work in experimental animal models and humans shows that diet has a much more pervasive and prominent role than previously thought in modulating neuroinflammatory and neurodegenerative mechanisms leading to some of the most common chronic central nervous system (CNS) diseases. Chronic or intermittent food restriction has profound effects in shaping brain and peripheral metabolism, immunity, and gut microbiome biology. Interactions among calorie intake, meal frequency, diet quality, and the gut microbiome modulate specific metabolic and molecular pathways that regulate cellular, tissue, and organ homeostasis as well as inflammation during normal brain aging and CNS neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis, among others. This review discusses these findings and their potential application to the prevention and treatment of CNS neuroinflammatory diseases and the promotion of healthy brain aging.
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http://dx.doi.org/10.1084/jem.20190086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802371PMC
February 2021

DNA damage in lens epithelial cells exposed to occupationally-relevant X-ray doses and role in cataract formation.

Sci Rep 2020 12 10;10(1):21693. Epub 2020 Dec 10.

Department of Medical Physics, St. Orsola-Malpighi University Hospital, Bologna, Italy.

The current framework of radiological protection of occupational exposed medical workers reduced the eye-lens equivalent dose limit from 150 to 20 mSv per year requiring an accurate dosimetric evaluation and an increase understanding of radiation induced effects on Lens cells considering the typical scenario of occupational exposed medical operators. Indeed, it is widely accepted that genomic damage of Lens epithelial cells (LEC) is a key mechanism of cataractogenesis. However, the relationship between apoptosis and cataractogenesis is still controversial. In this study biological and physical data are combined to improve the understanding of radiation induced effects on LEC. To characterize the occupational exposure of medical workers during angiographic procedures an INNOVA 4100 (General Electric Healthcare) equipment was used (scenario A). Additional experiments were conducted using a research tube (scenario B). For both scenarios, the frequencies of binucleated cells, micronuclei, p21-positive cells were assessed with different doses and dose rates. A Monte-Carlo study was conducted using a model for the photon generation with the X-ray tubes and with the Petri dishes considering the two different scenarios (A and B) to reproduce the experimental conditions and validate the irradiation setups to the cells. The simulation results have been tallied using the Monte Carlo code MCNP6. The spectral characteristics of the different X-ray beams have been estimated. All irradiated samples showed frequencies of micronuclei and p21-positive cells higher than the unirradiated controls. Differences in frequencies increased with the delivered dose measured with Gafchromic films XR-RV3. The spectrum incident on eye lens and Petri, as estimated with MCNP6, was in good agreement in the scenario A (confirming the experimental setup), while the mean energy spectrum was higher in the scenario B. Nevertheless, the response of LEC seemed mainly related to the measured absorbed dose. No effects on viability were detected. Our results support the hypothesis that apoptosis is not responsible for cataract induced by low doses of X-ray (i.e. 25 mGy) while the induction of transient p21 may interfere with the disassembly of the nuclear envelop in differentiating LEC, leading to cataract formation. Further studies are needed to better clarify the relationship we suggested between DNA damage, transient p21 induction and the inability of LEC enucleation.
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http://dx.doi.org/10.1038/s41598-020-78383-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728785PMC
December 2020

Adherence to a healthy lifestyle and multiple sclerosis: a case-control study from the UK Biobank.

Nutr Neurosci 2020 Dec 9:1-9. Epub 2020 Dec 9.

Charles Perkins Center, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.

Background: Multiple sclerosis (MS) is a common and disabling condition. The importance of healthy lifestyle for this disease is poorly explored.

Objective: To test whether adherence to healthier lifestyle patterns is associated with a lower presence of multiple sclerosis (MS).

Methods: By using a case-control design, we investigated the combined association of four healthy lifestyle-related factors (no current smoking, healthy diet, exercising regularly, body mass index <30 kg/m) and the prevalence of MS. A logistic regression analysis, adjusted for potential confounders, was used and data reported as odds ratios (ORs) with their 95% confidence intervals (CIs).

Results: 728 participants with MS were matched with healthy controls ( = 2,912) using a propensity score approach. In a multivariable analysis, compared to those who scored low in the composite lifestyle score (0-1 healthy lifestyle factors), people who adopted all four low risk lifestyle factors showed a 71% lower odds of having MS ( = 0.29; 95% CI: 0.15-0.56). Moreover, there was a strong linear trend, suggesting that the higher number of healthy lifestyle behaviors was associated with lower odds of having MS.

Conclusion: Following a healthy lifestyle is associated with a lower prevalence of MS. This association should be explored further in cohort studies.
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http://dx.doi.org/10.1080/1028415X.2020.1846357DOI Listing
December 2020

LC-N2G: a local consistency approach for nutrigenomics data analysis.

BMC Bioinformatics 2020 Nov 17;21(1):530. Epub 2020 Nov 17.

School of Mathematics and Statistics, The University of Sydney, Sydney, NSW, 2006, Australia.

Background: Nutrigenomics aims at understanding the interaction between nutrition and gene information. Due to the complex interactions of nutrients and genes, their relationship exhibits non-linearity. One of the most effective and efficient methods to explore their relationship is the nutritional geometry framework which fits a response surface for the gene expression over two prespecified nutrition variables. However, when the number of nutrients involved is large, it is challenging to find combinations of informative nutrients with respect to a certain gene and to test whether the relationship is stronger than chance. Methods for identifying informative combinations are essential to understanding the relationship between nutrients and genes.

Results: We introduce Local Consistency Nutrition to Graphics (LC-N2G), a novel approach for ranking and identifying combinations of nutrients with gene expression. In LC-N2G, we first propose a model-free quantity called Local Consistency statistic to measure whether there is non-random relationship between combinations of nutrients and gene expression measurements based on (1) the similarity between samples in the nutrient space and (2) their difference in gene expression. Then combinations with small LC are selected and a permutation test is performed to evaluate their significance. Finally, the response surfaces are generated for the subset of significant relationships. Evaluation on simulated data and real data shows the LC-N2G can accurately find combinations that are correlated with gene expression.

Conclusion: The LC-N2G is practically powerful for identifying the informative nutrition variables correlated with gene expression. Therefore, LC-N2G is important in the area of nutrigenomics for understanding the relationship between nutrition and gene expression information.
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http://dx.doi.org/10.1186/s12859-020-03861-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672905PMC
November 2020

Efficacy and Safety of Accelerated Corneal Cross-linking for Progressive Keratoconus: A 5-Year Follow-up Study.

J Refract Surg 2020 Nov;36(11):724-730

Purpose: To investigate the long-term efficacy and safety of continuous light-accelerated corneal cross-linking (CXL) in patients with progressive keratoconus.

Methods: This retrospective study analyzed 29 eyes of 29 consecutive patients with progressive keratoconus treated with epithelium-off riboflavin-ultraviolet induced accelerated CXL (30 mW/cm-7.2 joules/cm). Uncorrected (UDVA) and corrected (CDVA) distance visual acuity, keratometry measurements at 3 and 6 mm (Kmax, Kmin, and Kmean), topographic astigmatism, central corneal thickness, anterior corneal aberrometric analysis (at 3 and 6 mm), endothelial cell density, and central foveal thickness were evaluated before and 24 and 60 months after surgery.

Results: UDVA significantly improved at 60 months postoperatively (P = .028). Kmax and Kmean at 3 mm significantly decreased at 24 (P = .009 and .006, respectively) and 60 (P = .017 and .034, respectively) months postoperatively, whereas Kmin significantly decreased only at 24 months postoperatively (P = .032). Kmax at 6 mm significantly decreased at 24 and 60 months postoperatively (P = .035 and .027, respectively). Cylinder error significantly decreased at 24 and 60 months postoperatively (P = .001 and .023, respectively). Wavefront aberration variables remained unchanged after surgery, except for spherical aberration at 6 mm that decreased at 24 and 60 months postoperatively (P = .038 and .031, respectively) and trefoil at 0° that significantly decreased at 24 months postoperatively (P < .005). Endothelial cell density and central foveal thickness showed no changes from baseline.

Conclusions: Accelerated CXL was found to be effective in halting keratoconus progression and improving some of the visual, topographic, and wavefront aberration variables evaluated. High energy irradiance did not induce significant changes in corneal transparency, endothelial cell density, and central foveal thickness. [J Refract Surg. 2020;36(11):724-730.].
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http://dx.doi.org/10.3928/1081597X-20200819-01DOI Listing
November 2020

Modified big bubble technique of deep anterior lamellar keratoplasty.

J Cataract Refract Surg 2020 Nov 2. Epub 2020 Nov 2.

From the Eye Department, Apollo Hospitals, Jubilee Hills, Hyderabad, India (Fogla, Indumathy); Ophthalmology Unit, Azienda USL-IRCCS di Reggio, Emilia, Italy (Fontana).

A new technique of air injection is described for bigbubble deep anterior lamellar keratoplasty (DALK) in eyes with keratoconus, along with a comparative analysis of the original technique. 50 eyes were analyzed in each group. Average steep keratometry and anterior chamber depth distribution were comparable between the 2 groups. The average size of type 1 bubble achieved with single air injection (Group 1) was 7.8 + 0.4 mm (range 6.5 - 8.5mm), and with sequential air injection (Group 2) was 8.5 + 0.3 (range 8 - 9mm). (P < 0.001) Intraoperative complications of spontaneous bursting of bubble in 1 eye (2%), and peripheral microperforation in 3 eyes (6%) occurred only in group 1. The modified technique of big-bubble DALK using sequential air injection aided by paracentesis to lower intraocular pressure allowed enlargement of a type 1 bubble in a safe and controlled manner with minimal risk for complications.
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http://dx.doi.org/10.1097/j.jcrs.0000000000000469DOI Listing
November 2020

Comparison of Gonioscopy-assisted Transluminal Trabeculotomy Versus Trabeculectomy With Mitomycin C in Patients With Open-angle Glaucoma.

J Glaucoma 2021 Jan;30(1):101-108

Ophthalmology Unit, AUSL-IRCCS di Reggio Emilia.

Prcis: Trabeculectomy (TRAB) lowers the intraocular pressure (IOP) more than gonioscopy-assisted transluminal trabeculotomy (GATT) at 18 months, with a reduction in IOP of 30% or more and a significant reduction in the number of glaucoma medications compared with baseline.

Purpose: To compare the IOP-lowering efficacy of GATT with mitomycin-C augmented TRAB in patients with uncontrolled open-angle glaucoma.

Methods: Single-center, retrospective, comparative cohort study. One hundred ten consecutive patients (110 eyes) underwent GATT (n=61) or TRAB (n=49). The primary outcome measure was IOP reduction, defined as a percentage decrease ≥30% and absolute IOP≤18 mm Hg at 18 months with (qualified) or without (complete) medications. Secondary outcomes were visual field change, number of glaucoma medications, complications, and reintervention.

Results: The mean±SD baseline IOP was 30.04±7.5 and 27.59±4.70 (P=0.072) with the mean number of medications of 3.08±0.73 and 2.92±0.91 (P=0.310) in TRAB and GATT, respectively. At 18 months, the mean±SD IOP was 15.26±3.47 mm Hg and 12.48±4.58 mm Hg after GATT and TRAB, respectively (P=0.002). The percentage of IOP lowering from baseline was 56.05±17.72 after TRAB and 42.04±15.56 after GATT (P<0.001). Percentages of complete and qualified success were 59% and 27% after TRAB and 46% and 31% after GATT (P=0.353). No change in visual field loss was observed in both groups. The mean reduction in medications was 2.3±1.4 and 2.1±1.5 in TRAB and GATT, respectively (P=0.493). The most frequent complication after TRAB was hypotony and after GATT hyphema. Reintervention occurred in 8.2% of cases after TRAB and in 14.8% after GATT (P=0.341).

Conclusions: IOP lowering was greater after TRAB than after GATT at 18 months with a significant reduction in the number of medications after both procedures. Complications and reintervention occurred equally in both groups but differed in type.
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http://dx.doi.org/10.1097/IJG.0000000000001696DOI Listing
January 2021

Effectiveness of Infliximab and Interferon Alpha-2a for the Treatment of Behçet's Uveitis: Customizing Therapy according to the Clinical Features.

Ocul Immunol Inflamm 2020 Oct 6:1-9. Epub 2020 Oct 6.

Ocular Immunology Unit, Azienda USL-IRCCS of Reggio Emilia , Reggio Emilia, Italy.

Purpose: To report long term results of biologic treatment of severe and refractory Behçet's uveitis (BU) choosing a different biologic agent according to the uveitis clinical features.

Methods: Retrospective cohort of patients with BU refractory to conventional therapy, who received Interferon (IFN) alpha-2a or Infliximab (IFX) for at least 3 months.

Results: Twenty-two patients were included (mean age 29 ± 10 years, 63% males); Fifteen received IFN and 7 IFX, for a mean treatment period of 30 ± 24(SD) months. Twenty (90%) patients discontinued treatment, in most cases for complete remission (77%). Seven patients (32%) showed relapses during treatment and five (23%) after discontinuation. Visual acuity improved significantly in IFN group and all eyes showed a significant decrease in central macular thickness at 12 months.

Conclusions: Both IFX and IFN Alpha-2a were effective and well tolerated in the treatment of refractory BU using a customized approach based on the uveitis features.
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http://dx.doi.org/10.1080/09273948.2020.1815797DOI Listing
October 2020

Delayed-onset Bilateral Peripheral Posterior Interstitial Keratitis Associated with Epstein-Barr Virus-Induced Infectious Mononucleosis.

Ocul Immunol Inflamm 2020 Sep 18:1-4. Epub 2020 Sep 18.

Department of Ophthalmology, Azienda USL - IRCCS , Reggio Emilia, Italy.

Introduction: Epstein-Barr Virus (EBV) has been previously reported to cause rare occurrence of mostly epithelial and nummular keratitis. We hereby report two patients developing bilateral peripheral deep interstitial keratitis following EBV-related infectious mononucleosis (IM).

Description Of Cases: Two female adolescents presented with findings of chronic relapsing posterior interstitial keratitis with neovascularisation mostly located in the superior and inferior peripheral cornea, in absence of signs of anterior uveitis. The disease presented months after the occurrence of IM. Other etiologies of interstitial keratitis were excluded. EBV DNA could not be detected in the aqueous humor of both patients. The patients responded promptly to topical corticosteroids, with multiple recurrences reported in one case.

Conclusion: EBV-induced IM can cause bilateral peripheral interstitial keratitis with delayed onset. Progressive relapsing course of the keratitis can be observed.
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http://dx.doi.org/10.1080/09273948.2020.1811351DOI Listing
September 2020

Excisional penetrating keratoplasty for fungal interface keratitis after endothelial keratoplasty: surgical timing and visual outcome.

Int Ophthalmol 2021 Jan 17;41(1):363-373. Epub 2020 Sep 17.

Ophthalmology Unit, Azienda USL - IRCCS di Reggio Emilia, Viale Risorgimento 80, 42010, Reggio Emilia, Italy.

Purpose: In this paper, we describe two cases of fungal interface infectious keratitis (IIK) developed after endothelial keratoplasty (EK) who underwent delayed therapeutic penetrating keratoplasty (TPK) with a poor visual outcome. Furthermore, we conducted a review of the literature and analyzed the visual outcomes of TPK in relation to the time from IIK diagnosis.

Methods: We searched the literature for fungal IIK cases occurred after EK and treated by TPK. We identified 17 cases of fungal IIK, mostly caused by Candida spp. (88%).

Results: Infection was diagnosed at a median time of 21 (range 1-90 days) days after EK. The median lag time between infection diagnosis and TPK was 30 (range 7-393) days. The median distance corrected visual acuity (DCVA) measured 4-12 months after surgery was 20/40 (range 20/200-20/20). When TPK was performed within one month from diagnosis, the final median DCVA was 20/30 (range 20/100-20/20), with 83% of patients achieving ≥ 20/40 vision. When TPK was carried out later, the final median DCVA was 20/50 (range 20/200-20/22) with 44% of patients achieving ≥ 20/40 vision. One patient in the early surgery and four patients in the late surgery group showed postoperative DCVA ≤ 20/100 despite clear grafts.

Conclusion: TPK with removal of the sequestered infection is advocated as a safe and effective measure to treat a post-EK infection. Early surgery allows a reduced exposure time to infection and therefore may result in better visual outcomes and lower risk of complications caused by prolonged inflammation.
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http://dx.doi.org/10.1007/s10792-020-01576-1DOI Listing
January 2021

Effects of dietary restriction on gut microbiota and CNS autoimmunity.

Clin Immunol 2020 Aug 18:108575. Epub 2020 Aug 18.

Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA; Brain and Mind Centre, University of Sydney, Sydney, NSW 2050, Australia. Electronic address:

Multiple sclerosis (MS) is the most common central nervous system (CNS) autoimmune disease. It is due to the interplay of genetic and environmental factors. Current opinion is that diet could play a pathogenic role in disease onset and development. Dietary restriction (DR) without malnutrition markedly improves health and increases lifespan in multiple model organisms. DR regimens that utilize continuous or intermittent food restriction can induce anti-inflammatory, immuno-modulatory and neuroendocrine adaptations promoting health. These adaptations exert neuroprotective effects in the main MS animal model, experimental autoimmune encephalomyelitis (EAE). This review summarizes the current knowledge on DR-induced changes in gut microbial composition and metabolite production and its impact on underlying functional mechanisms. Studies demonstrating the protective effects of DR regimens on EAE and people with MS are also presented. This is a rapidly developing research field with important clinical implications for personalized dietary interventions in MS prevention and treatment.
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http://dx.doi.org/10.1016/j.clim.2020.108575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889763PMC
August 2020

One-port vs. three-port diagnostic vitrectomy for posterior segment diseases of unknown origin.

Int Ophthalmol 2020 Dec 9;40(12):3217-3222. Epub 2020 Jul 9.

Ocular Immunology, AUSL-IRCCS of Reggio Emilia, Reggio Emilia, Italy.

Purpose: To compare the safety and the effectiveness of one-port vs. three-port diagnostic vitrectomy in undiagnosed cases of posterior segment inflammation.

Methods: We retrospectively collected data from 80 consecutive diagnostic vitrectomies performed using a one-port (n = 40) or a three-port approach (n = 40). Cases of suspected postoperative endophthalmitis were not included in the study. Several variables were compared among groups, including length of surgery, postoperative best-corrected visual acuity (BCVA), diagnostic success and surgical complications.

Results: The mean duration of surgery was shorter in the one-port group when compared to the three-port group (15 ± 8 min vs. 49 ± 30; p = 0.0001). The patients were observed for a mean follow-up of 19 months (range 1-84). In the one-port group, the mean BCVA improved from 1.31 ± 0.96 to 0.57 ± 0.59 logarithm of minimum resolution (LogMAR) (p = 0.0009). In the three-port group, BCVA improved from 0.98 ± 0.76 to 0.51 ± 0.76 LogMAR (p = 0.0005). The difference in mean postoperative BCVA between groups was not significative at the last follow-up. One-port vitrectomy yields to a final diagnosis in 80% of the cases, and three-port vitrectomy in 48%. Most of the one-port vitrectomies were carried out under topical anesthesia. After surgery, in both groups three eyes developed a retinal detachment.

Conclusions: In this pilot study, the one-port diagnostic vitrectomy has proven to be as effective and safe as the three-port approach, allowing a reduction in surgical times. One-port diagnostic vitrectomy might be considered as the first option for those cases where more complex surgical procedures are not needed.
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http://dx.doi.org/10.1007/s10792-020-01504-3DOI Listing
December 2020

Ab interno intraluminal suture to reverse ocular hypotony after glaucoma drainage device implantation.

Eur J Ophthalmol 2020 Jun 16:1120672120936487. Epub 2020 Jun 16.

Ophthalmology Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy.

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http://dx.doi.org/10.1177/1120672120936487DOI Listing
June 2020

A novel intraocular lens designed for sutureless scleral fixation: surgical series.

Graefes Arch Clin Exp Ophthalmol 2021 Jan 11;259(1):257-262. Epub 2020 Jun 11.

IRCCS Fondazione G.B. Bietti ONLUS, Rome, Italy.

Purpose: To report a retrospective series of patients implanted with a novel hydrophilic acrylic single-piece intraocular lens (IOL) designed for sutureless scleral fixation (FIL-SSF Carlevale lens, Soleko, Italy) injectable through a 2.2-mm incision.

Methods: Seventy-eight patients with minimum 6-month follow-up were divided into 6 groups: dropped nucleus, luxated IOL, trauma, aphakia, IOL exchange, and Marfan's syndrome. Surgery included peritomy and scleral flap creation at 3 and 9 o'clock position. The IOL was then injected and grasped with 25G forceps through a hole created 2 mm posterior to the limbus underneath the sculped scleral flap.

Results: The study included 78 patients (mean age 71.9 ± 12.6 years) and average follow-up 10.2 ± 4.2 months. Average surgery duration was 69.4 ± 26.1 min and vision significantly improved from 0.86 ± 0.56 logMAR to 0.38 ± 0.42 logMAR at 6 months post-operative (p < 0.001). Intraoperative complications included corneal edema, retinal tears, and vitreous bleeding each in 2/78 patients (2.5%); 1/78 (1.3%) localized retinal detachment and 1/78 (1.3%) rupture of one T-shaped IOL harpoon. Post-operative complications included 4/78 (5.1%) cystoid macular edemas, 2/78 retinal tears, 2/78 retinal detachments, 2/78 developed ocular hypertension, and 1/78 corneal decompensation requiring DSAEK.

Conclusion: The Carlevale lens is designed for sutureless intrascleral fixation and can be successfully used in a variety of indications including difficult trauma cases with good rehabilitation. An implant requires experience and delicate manipulation.
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http://dx.doi.org/10.1007/s00417-020-04789-3DOI Listing
January 2021

Persistence of Inflammation After Uncomplicated Cataract Surgery: A 6-Month Laser Flare Photometry Analysis.

Adv Ther 2020 07 21;37(7):3223-3233. Epub 2020 May 21.

Ophthalmology Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy.

Purpose: To evaluate, by laser photometry, the persistency of anterior chamber flare after uneventful phacoemulsification in asymptomatic patients with no signs of inflammation on slit lamp examination.

Method: Seventy-five patients previously enrolled in a randomized clinical trial that evaluated inflammation after uneventful phacoemulsification in eyes treated with dexamethasone 0.1% ophthalmic suspension (group 1) or bromfenac 0.09% ophthalmic solution (group 2) for 2 weeks. Anterior chamber inflammation was investigated by laser flare photometry. At 30 days after surgery, laser flare showed persistently elevated values. For this reason, patients were further analyzed at 3 and 6 months. Additionally, optical coherence tomography was used to measure the central macular thickness (CMT) and to assess for postoperative pseudophakic macular edema.

Results: When compared to preoperative values, laser flare photometry demonstrated persistent ocular inflammation at postoperative days 90 and 180 in group 1, but not in group 2. Laser flare values showed a significant reduction in group 2 compared to group 1 throughout all the follow-up (p < 0.001). The increase in mean CMT at days 90 and 180 with respect to baseline was statistically significant in group 1 but not in group 2, in which it decreased to levels similar to preoperative value. Group 1 showed a higher increase in mean CMT compared to group 2 throughout all the follow-up (p < 0.001). The proportion of patients that developed pseudophakic cystoid macular edema (CME) was 14% (n = 5) and 0% (n = 0) in group 1 and group 2, respectively (p = 0.02). The bivariate analysis demonstrated a positive correlation between laser flare and CMT values in group 1 but not in group 2.

Conclusion: Anterior chamber inflammation persists for more than 30 days in a significant proportion of patients after uncomplicated cataract surgery and may be responsible for late onset of cystoid macular edema cases.

Trial Registration: ClinicalTrials.gov identifier, NCT03317847.
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http://dx.doi.org/10.1007/s12325-020-01383-1DOI Listing
July 2020

Impact of intermittent energy restriction on anthropometric outcomes and intermediate disease markers in patients with overweight and obesity: systematic review and meta-analyses.

Crit Rev Food Sci Nutr 2020 May 2:1-12. Epub 2020 May 2.

Institute for Evidence in Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

This systematic review aims to investigate the effects of intermittent energy restriction (IER) on anthropometric outcomes and intermediate disease markers. A systematic literature search was conducted in three electronic databases. Randomized controlled trials (RCTs) were included if the intervention lasted ≥12 weeks and IER was compared with either continuous energy restriction (CER) or a usual diet. Random-effects meta-analysis was performed for eight outcomes. Certainty of evidence was assessed using GRADE. Seventeen RCTs with 1328 participants were included. IER in comparison to a usual diet may reduce body weight (mean difference [MD]: -4.83 kg, 95%-CI: -5.46, -4.21;  = 6 RCTs), waist circumference (MD: -1.73 cm, 95%-CI: -3.69, 0.24;  = 2), fat mass (MD: -2.54 kg, 95%-CI: -3.78, -1.31;  = 6), triacylglycerols (MD: -0.20 mmol/L, 95%-CI: -0.38, -0.03;  = 5) and systolic blood pressure (MD: -6.11 mmHg, 95%-CI: -9.59, -2.64;  = 5). No effects were observed for LDL-cholesterol, fasting glucose, and glycosylated-hemoglobin. Both, IER and CER have similar effect on body weight (MD: -0.55 kg, 95%-CI: -1.01, -0.09;  = 13), and fat mass (MD: -0.66 kg, 95%-CI: -1.14, -0.19;  = 10), and all other outcomes. In conclusion, IER improves anthropometric outcomes and intermediate disease markers when compared to a usual diet. The effects of IER on weight loss are similar to weight loss achieved by CER.
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http://dx.doi.org/10.1080/10408398.2020.1757616DOI Listing
May 2020

Cytokine Profiling in Aqueous Humor Samples From Patients With Non-Infectious Uveitis Associated With Systemic Inflammatory Diseases.

Front Immunol 2020 10;11:358. Epub 2020 Mar 10.

Clinical Immunology, Allergy and Advanced Biotechnologies Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy.

Non-infectious uveitis are intraocular inflammatory conditions caused by dysregulated activation of the immune response without any detectable infectious agents. The aim of this study was to explore potential markers and therapeutic targets for two distinct types of non-infectious uveitis associated with Behçet's disease (BD) and Vogt Koyanagi Harada (VKH) disease. Concentrations of 27 cytokines were investigated in aqueous humor (AH) samples from patients with active uveitis vs. healthy controls (HC) ( = 10 patients with BD-associated uveitis; = 10 patients with VKH-associated uveitis; = 10 HC) using the Bio-Plex Pro human cytokine group I panel. Additionally, leukocytes in AH samples were counted with hemocytometers and characterized by flow cytometry. Eleven cytokines were differentially expressed between patients with uveitis and HC with a median concentration greater than 10 pg/ml. IL-6, IP-10, G-CSF, and IFNγ showed higher concentrations in AH samples from both BD and VKH patients while IL-2, IL-8, IL-13, TNFα, eotaxin, IL-1ra showed statistically significant higher concentrations only in AH samples from BD patients. GM-CSF was the sole cytokine with an opposite profile showing decreased levels in AH samples from BD patients. IL-1ra and IL-6 were detected at higher frequencies in AH samples from BD and VKH patients compared with those from HC while IFNγ and TNFα were not detected in HC. The concentrations of IL-6, IL-8, IP-10, G-CSF, IFNγ, TNFα, eotaxin, IL-1ra positively correlated with the concentrations of leukocytes in AH, suggesting that such cytokines can be produced by immune cells and/or attract and/or promote proliferation and survival of immune cells in these types of uveitis. The correlation matrix of cytokine concentrations in AH samples revealed that IFNγ, TNFα, eotaxin, IL-6, G-CSF highly correlated each other. The ratios of cytokine concentrations between AH and plasma intra-individuals showed that IL-2, IL-6, IP-10, GM-CSF were increased intraocularly. In conclusion, AH sampling followed by multiplex analysis of cytokines should be fostered in non-infectious uveitis to identify cytokines dysregulated intraocularly in each individual laying the groundwork for precision medicine.
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http://dx.doi.org/10.3389/fimmu.2020.00358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7077343PMC
March 2020

Measuring Anterior Chamber Inflammation After Cataract Surgery: A Review of the Literature Focusing on the Correlation with Cystoid Macular Edema.

Clin Ophthalmol 2020 9;14:41-52. Epub 2020 Jan 9.

Ophthalmology Unit, AUSL-IRCCS of Reggio Emilia, Reggio Emilia, Italy.

Cystoid macular edema (CME) is an infrequent, though potentially visually impairing, complication after uneventful cataract surgery. Rupture of the blood-aqueous barrier, with leakage of serum proteins into the aqueous humour, is the main pathogenic factor. However, only a few studies investigated the potential correlation between anterior chamber (AC) inflammation and the risk of cystoid macular changes occurring after surgery. This review aims to identify evidence of a correlation between AC inflammation and the risk of pseudophakic CME. One hundred eighty-seven prospective trials investigating AC inflammation after uncomplicated cataract surgery were identified. Methods of analysis of AC inflammation and the frequency of macular changes were recorded. In the majority (51%) of the studies, inflammation was assessed by clinical grading, followed by laser flare and cell photometry (LFCP) (42%) and aqueous humour sample (4%). Few studies (4%) adopted a combined LFCP and aqueous sample or clinical grading analysis. Sixteen (9%) studies investigated AC inflammation and macular changes by OCT (7%) or fluorescein angiography (2%). Correlation between the amount of postoperative AC inflammation and frequency of CME was documented in 7 studies, not confirmed in 2 studies, and not examined in the other 7. LFCP, more than the other methods of analysis, correlated with the frequency of CME postoperatively. Investigation of the relationship between AC inflammation and the risk of CME changes requires the adoption of quantitative methods of analysis of the inflammatory response after surgery. For this purpose, due to the low level of inflammation in the AC after uncomplicated cataract surgery, LFCP, more than subjective clinical grading, seems a more sensitive and reproducible method of measurement. Inflammation assessment after cataract surgery has a potential role in predicting the risk of CME development and may help to titrate the duration and intensity of treatment in relation to the surgical inflammatory response.
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http://dx.doi.org/10.2147/OPTH.S237405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957928PMC
January 2020

Associations between body mass index, waist circumference and erectile dysfunction: a systematic review and META-analysis.

Rev Endocr Metab Disord 2020 Dec;21(4):657-666

National Research Council, Neuroscience Institute, Aging Branch, 35128, Padova, Italy.

Growing evidence reports that obesity might play a role in erectile dysfunction (ED), but limited knowledge is available. We conducted a meta-analysis to estimate the prevalence of ED in overweight men and men with obesity. We performed a systematic review up to 01/04/2019 to investigate the associations between obesity and ED. Applying a random-effect model, we calculated the prevalence of ED, the odds ratio (OR) for the presence of ED by Body Mass Index (BMI) categories and the mean differences between ED and controls in BMI and Waist Circumference (WC). Among 3409 studies, we included 45 articles with 42,489 men (mean age = 55 years). Taking normal weight men as reference, the prevalence of ED was significantly higher in overweight (OR = 1.31; 95%CI: 1.13-1.51; I = 72%) and in men with obesity (OR = 1.60; 95%CI: 1.29-1.98; I = 79%). Adjusting our analyses for potential confounders, the results were confirmed in men with obesity (OR = 1.46; 95%CI: 1.24-1.72; I = 72%). ED was associated with significant higher values of BMI (MD = 0.769; 95%CI: 0.565-0.973 Kg/m; I = 78%) and WC (MD = 5.251 cm; 95%CI: 1.295-9.208; I = 96%). Considering the high prevalence of ED among men with obesity, clinicians should screen for this clinical condition in this population. Findings from the present study suggest that reducing adiposity is a crucial approach in patients with ED who are affected by obesity.
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http://dx.doi.org/10.1007/s11154-020-09541-0DOI Listing
December 2020

Blood derived treatment from two allogeneic sources for severe dry eye associated to keratopathy: a multicentre randomised cross over clinical trial.

Br J Ophthalmol 2020 08 19;104(8):1142-1147. Epub 2019 Nov 19.

Emilia Romagna Cord Blood Bank-Transfusion Service, AOU of Bologna Sant'Orsola-Malpighi Teaching Hospital, Bologna, Italy.

Aim: To compare the efficacy of cord blood and peripheral adult donor blood serum eyedrops, controlled for growth factor content, in the treatment of severe dry eye diseases (DED) resistant to conventional therapy.

Methods: This was a multicentre randomised, double-masked, cross-over clinical trial. Sixty patients diagnosed as severe DED, associated to persistent corneal epithelial defects were randomised and equally assigned to group A (treated with cord blood serum (CBS)) or group B (treated with PBS), eyedrops administered eight times/day for 1 month. Primary outcome was the pretreatment and post-treatment change in corneal fluorescein staining. Secondary outcomes included the pretreatment and post-treatment change in Ocular Surface Disease Index (OSDI) questionnaire and Visual Analogue Score (VAS) of subjective symptoms, Schirmer I test, tear break-up time and conjunctival staining. Patients with relapse in signs or symptoms after further 2 months switched to the remaining group for one additional month. Data were statistically analysed (p<0.05).

Results: Corneal staining was more significantly reduced after the CBS treatment, both VAS and OSDI score reduction was observed in both groups, but group A reported significantly less grittiness and pain. Nineteen patients shifted in the crossover period, the within individual comparison confirmed a better recovery in the CBS treatment period. Reduction in epithelial damage was positively associated with epidermal growth factor, transforming growth factorα and platelet-derived growth factor content. Levels of interleukins (IL-13) were positively associated with symptom decrease.

Conclusions: Overall, DED signs improved after both CBS and PBS treatments, with potential advantages of CBS for subjective symptoms and corneal damage reduction.

Clinical Trial Registration: NCT03064984.
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http://dx.doi.org/10.1136/bjophthalmol-2019-314859DOI Listing
August 2020

A word of caution against excessive protein intake.

Nat Rev Endocrinol 2020 01 14;16(1):59-66. Epub 2019 Nov 14.

Center for Human Nutrition, Washington University School of Medicine, St Louis, MO, USA.

Dietary protein is crucial for human health because it provides essential amino acids for protein synthesis. In addition, dietary protein is more satiating than carbohydrate and fat. Accordingly, many people consider the protein content when purchasing food and beverages and report 'trying to eat more protein'. The global market for protein ingredients is projected to reach approximately US$90 billion by 2021, largely driven by the growing demand for protein-fortified food products. This Perspective serves as a caution against the trend of protein-enriched diets and provides an evidence-based counterpoint that underscores the potential adverse public health consequences of high protein intake.
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http://dx.doi.org/10.1038/s41574-019-0274-7DOI Listing
January 2020

Iridocorneal endothelial syndrome in a patient with keratoconus - a case report.

BMC Ophthalmol 2019 Nov 11;19(1):221. Epub 2019 Nov 11.

Ophthalmology Unit, AUSL-IRCCS of Reggio Emilia, Reggio Emilia, Italy.

Background: To describe a case of a rare association of bilateral keratoconus and unilateral essential iris atrophy and to conduct a literature review of the current strategies of treatment of the corneal disease and glaucoma in patients with Iridocorneal Endothelial Syndrome (ICE).

Case Presentation: We report a rare association of bilateral keratoconus and unilateral essential iris atrophy in a 38-year-old man. Diagnosis of bilateral keratoconus was confirmed by corneal topography. Slit-lamp examination showed extensive iris atrophy with corectopia and policoria in one eye. Corneal specular microscopy revealed an abnormal endothelium morphology in the same eye with extensive peripheral anterior synechiae and closure of the drainage angle at gonioscopy. Intraocular pressure was 26 mmHg, despite maximal topical therapy. Optic disc examination showed severe glaucomatous cupping. Surgery by glaucoma drainage device implantation was performed.

Conclusion: Essential iris atrophy is a rare clinical variant of ICE syndrome characterized by profound anatomical alterations of the anterior segment associated with corneal edema and secondary glaucoma. In these patients, selective keratoplasties have replaced penetrating keratoplasty to treat corneal decompensation and glaucoma drainage devices are preferred to conventional trabeculectomy for the treatment of secondary glaucoma.
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http://dx.doi.org/10.1186/s12886-019-1215-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849214PMC
November 2019

Anterior Chamber Inflammation After Cataract Surgery: A Randomized Clinical Trial Comparing Bromfenac 0.09% to Dexamethasone 0.1.

Adv Ther 2019 10 3;36(10):2712-2722. Epub 2019 Sep 3.

Ophthalmology Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy.

Purpose: To compare the efficacy of bromfenac 0.09% and dexamethasone 0.1% in the treatment of anterior chamber inflammation after uncomplicated cataract surgery.

Methods: Seventy-six patients with senile cataracts and no other ocular comorbidities who underwent uneventful phacoemulsification were randomized 1:1 to receive dexamethasone ophthalmic suspension 0.1% or bromfenac ophthalmic solution 0.09% for 2 weeks. All patients were examined on the day before surgery and postoperatively at day 1, 3, 7, 9, 11, 14 and 30. Laser flare photometry was used to quantify anterior chamber inflammation and optical coherence tomography to measure macular thickness.

Results: Bromfenac was as effective as dexamethasone in reducing inflammation in the anterior chamber of the eye. Laser flare increased the day after surgery and progressively decreased after starting the treatment with no statistically significant difference between dexamethasone and bromfenac at all time points. Visual acuity improved steadily after surgery in both groups. Mean macular thickness was similar in both the dexamethasone and bromfenac arms at 1 month.

Conclusions: Short-term therapy with topical bromfenac alone is as effective as dexamethasone in low-risk cataract surgery patients.

Trial Registration: ClinicalTrials.gov # NCT03317847; EudraCT # 2016-004358-14.

Funding: Santa Maria Nuova Hospital IRCCS, Reggio Emilia, Italy.
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http://dx.doi.org/10.1007/s12325-019-01076-4DOI Listing
October 2019

Re: "Deep Anterior Lamellar Keratoplasty in Eyes With Intrastromal Corneal Ring Segments".

Cornea 2019 11;38(11):e53

Ophthalmology Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy.

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http://dx.doi.org/10.1097/ICO.0000000000002099DOI Listing
November 2019

2 years of calorie restriction and cardiometabolic risk (CALERIE): exploratory outcomes of a multicentre, phase 2, randomised controlled trial.

Lancet Diabetes Endocrinol 2019 09 11;7(9):673-683. Epub 2019 Jul 11.

Department of Medicine, Washington University School of Medicine, St Louis, MO, USA; Department of Clinical and Experimental Sciences, Brescia University, Brescia, Italy; School of Medicine and Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia.

Background: For several cardiometabolic risk factors, values considered within normal range are associated with an increased risk of cardiovascular morbidity and mortality. We aimed to investigate the short-term and long-term effects of calorie restriction with adequate nutrition on these risk factors in healthy, lean, or slightly overweight young and middle-aged individuals.

Methods: CALERIE was a phase 2, multicentre, randomised controlled trial in young and middle-aged (21-50 years), healthy non-obese (BMI 22·0-27·9 kg/m) men and women done in three clinical centres in the USA. Participants were randomly assigned (2:1) to a 25% calorie restriction diet or an ad libitum control diet. Exploratory cardiometabolic risk factor responses to a prescribed 25% calorie restriction diet for 2 years were evaluated (systolic, diastolic, and mean blood pressure; plasma lipids; high-sensitivity C-reactive protein; metabolic syndrome score; and glucose homoeostasis measures of fasting insulin, glucose, insulin resistance, and 2-h glucose, area-under-the curve for glucose, and insulin from an oral glucose tolerance test) analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00427193.

Findings: From May 8, 2007, to Feb 26, 2010, of 238 participants that were assessed, 218 were randomly assigned to and started a 25% calorie restriction diet (n=143, 66%) or an ad libitum control diet (n=75, 34%). Individuals in the calorie restriction group achieved a mean reduction in calorie intake of 11·9% (SE 0·7; from 2467 kcal to 2170 kcal) versus 0·8% (1·0) in the control group, and a sustained mean weight reduction of 7·5 kg (SE 0·4) versus an increase of 0·1 kg (0·5) in the control group, of which 71% (mean change in fat mass 5·3 kg [SE 0·3] divided by mean change in weight 7·5 kg [0·4]) was fat mass loss. Calorie restriction caused a persistent and significant reduction from baseline to 2 years of all measured conventional cardiometabolic risk factors, including change scores for LDL-cholesterol (p<0·0001), total cholesterol to HDL-cholesterol ratio (p<0·0001), and systolic (p<0·0011) and diastolic (p<0·0001) blood pressure. In addition, calorie restriction resulted in a significant improvement at 2 years in C-reactive protein (p=0·012), insulin sensitivity index (p<0·0001), and metabolic syndrome score (p<0·0001) relative to control. A sensitivity analysis revealed the responses to be robust after controlling for relative weight loss changes.

Interpretation: 2 years of moderate calorie restriction significantly reduced multiple cardiometabolic risk factors in young, non-obese adults. These findings suggest the potential for a substantial advantage for cardiovascular health of practicing moderate calorie restriction in young and middle-aged healthy individuals, and they offer promise for pronounced long-term population health benefits.

Funding: National Institute on Aging and National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health.
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http://dx.doi.org/10.1016/S2213-8587(19)30151-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6707879PMC
September 2019

Reply.

Cornea 2019 09;38(9):e41-e42

Ophthalmology Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy.

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http://dx.doi.org/10.1097/ICO.0000000000002030DOI Listing
September 2019

Aging, lifestyle and dementia.

Neurobiol Dis 2019 10 25;130:104481. Epub 2019 May 25.

Charles Perkins Centre, University of Sydney, Sydney 2006, Australia; School of Life and Environmental Sciences, University of Sydney, Sydney 2006, Australia.

Aging is the greatest risk factor for most diseases including cancer, cardiovascular disorders, and neurodegenerative disease. There is emerging evidence that interventions that improve metabolic health with aging may also be effective for brain health. The most robust interventions are non-pharmacological and include limiting calorie or protein intake, increasing aerobic exercise, or environmental enrichment. In humans, dietary patterns including the Mediterranean, Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) and Okinawan diets are associated with improved age-related health and may reduce neurodegenerative disease including dementia. Rapamycin, metformin and resveratrol act on nutrient sensing pathways that improve cardiometabolic health and decrease the risk for age-associated disease. There is some evidence that they may reduce the risk for dementia in rodents. There is a growing recognition that improving metabolic function may be an effective way to optimize brain health during aging.
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http://dx.doi.org/10.1016/j.nbd.2019.104481DOI Listing
October 2019

Management of Descemet Membrane's Folds After Deep Anterior Lamellar Keratoplasty: Descemet Membrane-Tucking Technique.

Cornea 2019 Jun;38(6):772-774

Ophthalmology Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy.

Purpose: To describe a surgical maneuver that allows for correction of central Descemet membrane (DM) folds at the end of a deep anterior lamellar keratoplasty (DALK) procedure. We term the present technique "DM tucking."

Methods: A blunt tip spatula is introduced vertically into the trephination cut, 90 degrees away from the main direction of the DM folds, and advanced until it touches the host layer. Gentle pressure is applied, resulting in tucking of the redundant host layer toward the periphery. The tucking maneuver is repeated at different clock hours until a regular graft-host interface is obtained.

Results: We applied the present technique to several DALK procedures performed for keratoconus, and found it to be safe and effective.

Conclusions: DALK is the procedure of choice for the surgical treatment of corneal stromal diseases with a healthy endothelium, such as keratoconus. DM folds are a possible complication after DALK in patients with advanced corneal ectasia, arising from the compression of the redundant host DM by the donor graft, once it is sutured to the recipient. DM folds after DALK, when they involve the visual axis, cause permanent visual disturbances DM tucking allows the displacement of the central DM folds toward the graft margin, where they do not affect the patient's quality of vision.
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http://dx.doi.org/10.1097/ICO.0000000000001910DOI Listing
June 2019

The historical context and scientific legacy of John O. Holloszy.

J Appl Physiol (1985) 2019 08 7;127(2):277-305. Epub 2019 Feb 7.

Department of Nutrition and Dietetics, Doisy College of Health Science, St. Louis University, St. Louis, Missouri.

John O. Holloszy, as perhaps the world's preeminent exercise biochemist/physiologist, published >400 papers over his 50+ year career, and they have been cited >41,000 times. In 1965 Holloszy showed for the first time that exercise training in rodents resulted in a doubling of skeletal muscle mitochondria, ushering in a very active era of skeletal muscle plasticity research. He subsequently went on to describe the consequences of and the mechanisms underlying these adaptations. Holloszy was first to show that muscle contractions increase muscle glucose transport independent of insulin, and he studied the mechanisms underlying this response throughout his career. He published important papers assessing the impact of training on glucose and insulin metabolism in healthy and diseased humans. Holloszy was at the forefront of rodent studies of caloric restriction and longevity in the 1980s, following these studies with important cross-sectional and longitudinal caloric restriction studies in humans. Holloszy was influential in the discipline of cardiovascular physiology, showing that older healthy and diseased populations could still elicit beneficial cardiovascular adaptations with exercise training. Holloszy and his group made important contributions to exercise physiology on the effects of training on numerous metabolic, hormonal, and cardiovascular adaptations. Holloszy's outstanding productivity was made possible by his mentoring of ~100 postdoctoral fellows and substantial NIH grant funding over his entire career. Many of these fellows have also played critical roles in the exercise physiology/biochemistry discipline. Thus it is clear that exercise biochemistry and physiology will be influenced by John Holloszy for numerous years to come.
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http://dx.doi.org/10.1152/japplphysiol.00669.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732442PMC
August 2019

Trends in age-related disease burden and healthcare utilization.

Aging Cell 2019 02 29;18(1):e12861. Epub 2018 Nov 29.

Charles Perkins Center and Central Clinical School, University of Sidney, Sidney, New South Wales.

Aging is a strong risk factor for many chronic diseases. However, the impact of an aging population on the prevalence of chronic diseases and related healthcare costs are not known. We used a prevalence-based approach that combines accurate clinical and drug prescription data from Health Search CSD-LPD. This is a longitudinal observational data set containing computer-based patient records collected by Italian general practitioners (GP) and up-to-date healthcare expenditures data from the SiSSI Project. The analysis is based on data collected by 900 GP on an unbalanced sample of more than 1 million patients aged 35+, observed in different time periods between 2005 and 2014. In 2014, 86% of the Italian adults older than 65 had at least one chronic condition, and 56.7% had two or more. Prevalence of multiple chronic diseases and healthcare utilization increased among older and younger adults between 2004 and 2014. Indeed, in the last 10 years, average number of prescriptions increased by approximately 26%, while laboratory and diagnostic tests by 27%. The average number of DDD prescribed increased with age in all the observed years (from 114 in 2005 to 119.9 in 2014 for the 35-50 age group and from 774.9 to 1,178.1 for the 81+ patients). The alarming rising trends in the prevalence of chronic disease and associated healthcare costs in Italy, as well as in many other developed countries, call for an urgent implementation of interventions that prevent or slow the accumulation of metabolic and molecular damage associated with multiple chronic disease.
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http://dx.doi.org/10.1111/acel.12861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351821PMC
February 2019