Insights into the Role of Vitamin D in the Prevention and Control of Cancer and Other Chronic Noncommunicable Diseases: Shedding Further Light on a Captivating Subject.

Vitamin D is a hormone that humans can synthesize upon sun exposure or through a balanced and healthy diet, including vitamin D-rich foods or supplements [...].

Ribonucleotide reductase inhibition improves the symptoms of a Caenorhabditis elegans model of Alzheimer's disease.

Alzheimer's disease is the main cause of aging-associated dementia, for which there is no effective treatment. In this work, we reanalyze the information of a previous genome wide association study, using a new pipeline design to identify novel potential drugs. With this approach, ribonucleoside-diphosphate reductase gene (RRM2B) emerged as a candidate target and its inhibitor, 2', 2'-difluoro 2'deoxycytidine (gemcitabine), as a potential pharmaceutical drug against Alzheimer's disease. We functionally verified the effect of inhibiting the RRM2B homolog, rnr-2, in an Alzheimer's model of Caenorhabditis elegans, which accumulates human Aß1-42 peptide to an irreversible paralysis. RNA interference against rnr-2 and also treatment with 200 ng/ml of gemcitabine, showed an improvement of the phenotype. Gemcitabine treatment increased the intracellular ATP level 3.03 times, which may point to its mechanism of action. Gemcitabine has been extensively used in humans for cancer treatment but at higher concentrations. The 200 ng/ml concentration did not exert a significant effect over cell cycle, or affected cell viability when assayed in the microglia N13 cell line. Thus, the inhibitory drug of the RRM2B activity could be of potential use to treat Alzheimer's disease and particularly gemcitabine might be considered as a promising candidate to be repurposed for its treatment.

Artificial intelligence-based fluid quantification and associated visual outcomes in a real-world, multicentre neovascular age-related macular degeneration national database.

AIM: To explore associations between artificial intelligence (AI)-based fluid compartment quantifications and 12 months visual outcomes in OCT images from a real-world, multicentre, national cohort of naïve neovascular age-related macular degeneration (nAMD) treated eyes. METHODS: Demographics, visual acuity (VA), drug and number of injections data were collected using a validated web-based tool. Fluid compartment quantifications including intraretinal fluid (IRF), subretinal fluid (SRF) and pigment epithelial detachment (PED) in the fovea (1 mm), parafovea (3 mm) and perifovea (6 mm) were measured in nanoliters (nL) using a validated AI-tool. RESULTS: 452 naïve nAMD eyes presented a mean VA gain of +5.5 letters with a median of 7 injections over 12 months. Baseline foveal IRF associated poorer baseline (44.7 vs 63.4 letters) and final VA (52.1 vs 69.1), SRF better final VA (67.1 vs 59.0) and greater VA gains (+7.1 vs +1.9), and PED poorer baseline (48.8 vs 57.3) and final VA (55.1 vs 64.1). Predicted VA gains were greater for foveal SRF (+6.2 vs +0.6), parafoveal SRF (+6.9 vs +1.3), perifoveal SRF (+6.2 vs -0.1) and parafoveal IRF (+7.4 vs +3.6, all p<0.05). Fluid dynamics analysis revealed the greatest relative volume reduction for foveal SRF (-16.4 nL, -86.8%), followed by IRF (-17.2 nL, -84.7%) and PED (-19.1 nL, -28.6%). Subgroup analysis showed greater reductions in eyes with higher number of injections. CONCLUSION: This real-world study describes an AI-based analysis of fluid dynamics and defines baseline OCT-based patient profiles that associate 12-month visual outcomes in a large cohort of treated naïve nAMD eyes nationwide.

Prevention of tobacco use in an adolescent population through a multi-personal intervention model.

INTRODUCTION: The study aimed to assess the impact of a new intervention proposal involving students, teachers, and parents on smoking prevalence in secondary school adolescents. METHODS: A quasi-experimental study was conducted, in which the response to a preventive multi-personal intervention model (intervention) against tobacco consumption was compared with a standard anti-smoking activity carried out by the local government administration (control). The study was carried out during the 2017-2018 academic year. The study population included 306 students (intervention 151, control 155) with a mean age of 13.4 years. The model involved the parents, the students (aged 15-17 years), and the teachers. The primary outcome was the change in smoking status one year after the intervention. RESULTS: The percentage of non-smokers increased from 84.1% to 88.7% in the intervention group and remained almost unchanged among controls (89.3% vs 89.9%). After one year, there was an increase in the prevalence of non-smokers of 4.6% and a decrease in the prevalence of smokers of 4.7% among students who received the multi-personal intervention, whereas changes among controls were almost negligible (there was in fact a slight increase in the prevalence of smokers of 0.9%). The students who received the intervention smoked less or quit smoking more than those in the control group (OR=0.135; 95% CI: 0.019-0.973, p=0.047). CONCLUSIONS: The multi-personal model developed in the study with the participation of teachers and parents focused on students was feasible, and effectively reduced the prevalence of smoking among high school adolescents.

The Relationship between Depressive Symptoms, Quality of Life and miRNAs 8 Years after Bariatric Surgery.

(1) Background: There are conflicting results on whether weight loss after bariatric surgery (BS) might be associated with quality of life (QoL)/depressive symptomatology. We aim to determine whether BS outcomes are associated with QoL/depressive symptomatology in studied patients at the 8-year follow-up after BS, as well as their relationship with different serum proteins and miRNAs. (2) Methods: A total of 53 patients with class III obesity who underwent BS, and then classified into "good responders" and "non-responders" depending on the percentage of excess weight lost (%EWL) 8 years after BS (%EWL ≥ 50% and %EWL < 50%, respectively), were included. Basal serum miRNAs and different proteins were analysed, and patients completed tests to evaluate QoL/depressive symptomatology at 8 years after BS. (3) Results: The good responders group showed higher scores on SF-36 scales of physical functioning, role functioning-physical, role functioning-emotional, body pain and global general health compared with the non-responders. The expression of hsa-miR-101-3p, hsa-miR-15a-5p, hsa-miR-29c-3p, hsa-miR-144-3p and hsa-miR-19b-3p were lower in non-responders. Hsa-miR-19b-3p was the variable associated with the response to BS in a logistic regression model. (4) Conclusions: The mental health of patients after BS is limited by the success of the intervention. In addition, the expression of basal serum miRNAs related to depression/anxiety could predict the success of BS.

Diagnosis and Management of Patients With Geographic Atrophy Secondary to Age-Related Macular Degeneration: A Delphi Consensus Exercise.

Geographic atrophy (GA) is a progressive and irreversible retinal disease with no comprehensive recommendations for diagnosis or monitoring. We used a Delphi approach to determine consensus in key areas around diagnosis and management of GA. A steering committee of eight retina specialists developed two sequential online surveys administered to eye care professionals (ECPs). Consensus was defined as agreement by ≥ 75% of respondents. Up to 177 ECPs from eight countries completed one or both surveys. Consensus was achieved in several topics related to diagnostic imaging, including the use of optical coherence tomography, and the urgent need for treatments and beneficial interventions to reduce the associated burden. Currently, low-vision aids and smoking cessation are considered the most beneficial interventions. We demonstrate consensus for diagnosis and management of patients with GA including best practices in patient identification and monitoring, and unmet needs. [Ophthalmic Surg Lasers Imaging Retina 2023;54:589-598.].

Retinal phototoxicity after macular hole surgery in a patient under paclitaxel.

BACKGROUND: The purpose is to report the second case, to our knowledge, of suspected paclitaxel-induced phototoxic maculopathy following pars plana vitrectomy surgery. CASE PRESENTATION: 63-year-old phakic female who underwent an uneventful phaco-vitrectomy to treat a complete macular hole, developing macular phototoxicity in the post-operatively period that could not be explained by the surgery itself and could only be attributed to a possible photosensitization induced by the previous use of paclitaxel. CONCLUSIONS: The use of paclitaxel has been widely extended as a chemotherapy drug to treat breast cancer. It works by altering the intracellular microtubular reorganization and, based on this mechanism of action, photosensitivity has been previously described. We report a case of suspected paclitaxel-induced macular phototoxicity following ocular endoillumination during vitrectomy surgery.

"The Role of Vitamin D in Cancer Prevention": Some New Clues on a Fascinating Subject.

Increasing evidence from experimental animal nutrition studies suggests that vitamin D may potentially influence apoptosis and tumor-associated angiogenesis, reduce the initiation of carcinogenesis, and delay the multiplication and proliferation of tumor cells [...].

Characteristics of tobacco use among secondary school students: a cross-sectional study in a school in Valencia, Spain.

Introduction: Cigarette smoking is a significant public health problem, and it is essential to work actively with young people to limit the incorporation of this addiction. This study aimed to identify characteristics associated with tobacco use in adolescents in a real setting. Methods: Epidemiologic, cross-sectional study including secondary school students aged 12-17 years in the 1st, 2nd, and 3rd grades of "Joan Fuster High School" in the city of Sueca, Valencia (Spain). An anonymous, self-administered questionnaire was used to collect data on demographics, cigarette smoking history, alcohol consumption, nicotine dependence, and exposure to parental cigarette smoking. Results: The final sample of individuals surveyed included 306 students (50.6% females) with a median age of 13 years. The prevalence of cigarette smoking was 11.8% (13.5% in females and 9.9% in males). The mean age of cigarette smoking onset was 12.7 ± 1.6 years. Ninety-three students (30.4%) were repeaters, and 114 (37.3%) reported alcohol consumption. Significant factors associated with tobacco use were being a repeater (odds ratio [OR] 4.19, 95% confidence interval [CI] 1.75-10.55, p = 0.002), alcohol consumption (OR 4.06, 95% CI 1.75-10.15, p = 0.002) and parental cigarette smoking (OR 3.76, 95% CI 1.52-10.74, p = 0.007). Discussion: An operational profile of features associated with tobacco consumption was identified in the presence of parental cigarette smoking, alcohol consumption, and poor academic performance. Consideration of these factors could be useful in the operational design of cigarette smoking cessation interventions for young people in a context where there is a great need for better prevention and control of cigarette smoking.

Hypertension and hypercholesterolemia are predictive factors associated with type 2 diabetes persistence after metabolic surgery: A prospective study.

BACKGROUND: Metabolic surgery is the most effective therapeutic strategy for the management of type 2 diabetes (T2DM). Several preoperative clinical factors have been associated with T2DM remission after metabolic surgery. However, other potential predictors remain unexplored. AIM: To assess the role of basal (pre-surgery) clinical and biochemical parameters in T2DM remission after metabolic surgery. METHODS: A prospective study including 98 patients with T2DM undergoing metabolic surgery was performed. Clinical, anthropometric, and biochemical data were collected at baseline and 1 year following metabolic surgery. RESULTS: Patients without T2DM remission 1 year after metabolic surgery presented a longer duration of diabetes and higher glycated hemoglobin (HbA1c) levels; a higher percentage of these subjects were using insulin therapy, antihypertensive drugs, and lipid-lowering therapies before metabolic surgery, compared to those patients with T2DM remission. A lower percentage of T2DM remission after metabolic surgery was observed among patients with hypertension/hypercholesterolemia before surgery, compared to those patients without hypertension/hypercholesterolemia (51.7 % vs 86.8 %, p < 0.001, and 38.5 % vs 75 %, p < 0.001, respectively), and among patients with longer duration of diabetes (≥5 years vs <5 years; 44.4 % vs 83 %, respectively; p < 0.001). In the logistic regression model, diabetes duration, basal HbA1c, and the presence of hypertension and hypercholesterolemia before surgery were inversely related to T2DM remission following metabolic surgery, after adjusting for sex, age, waist circumference, and type of surgery. CONCLUSIONS: In a cohort of patients with obesity and T2DM, preoperative hypertension and hypercholesterolemia, together with a longer diabetes duration and higher HbA1c concentrations, were independent predictors of T2DM persistence after metabolic surgery.

OPHTHALMOLOGIC INVOLVEMENT IN PATIENTS WITH HEREDITARY TRANSTHYRETIN AMYLOIDOSIS.

PURPOSE: The aim of this study was to determine the ophthalmologic involvement in patients with hereditary transthyretin amyloidosis and its correlation with the mutations described in the literature. METHODS: Cross-sectional, noninterventional study. Fifty-two eyes of 26 consecutive patients diagnosed with hereditary transthyretin amyloidosis who visited the Puerta de Hierro-Majadahonda University Hospital from September 2019 to March 2022. All patients underwent complete ophthalmologic examination and multimodal imaging. Cardiologic, neurologic, digestive, and renal examinations were also recorded. RESULTS: Eighteen eyes of the total (34.61%) showed amyloid-related ocular involvement, vitreous amyloid deposits being the most common ocular manifestation (18/52). Statistically significant differences were found for the presence of vitreous amyloid deposits ( P < 0.01), crystalline amyloid deposits ( P < 0.05), parenchymal amyloid deposits ( P < 0.01), and vascular alterations ( P < 0.01) when comparing affected and unaffected eyes. Moreover, affected eyes showed worse best-corrected visual acuity ( P < 0.01). CONCLUSION: Ocular manifestations are present in a substantial number of patients with ATTR that could potentially lead to devastating consequences to patients' best-corrected visual acuity and quality of life. Therefore, it is important to emphasize the importance of multidisciplinary management and ophthalmologic assessment, follow-up and surgical treatment when necessary. To the best of our knowledge, this represents the largest series in Spain of amyloidosis' ophthalmologic involvement.

Early-switch versus late-switch in patients with diabetic macular edema: a cost-effectiveness study.

BACKGROUND: To evaluate the cost-effectiveness of early- versus late-switch to the intravitreal-dexamethasone implant (DEX-i) in patients with diabetic macular edema (DME) who did not adequately respond to vascular endothelial growth factor inhibitors (anti-VEGF). METHODS: Retrospective analysis of a multicenter Clinical Data Registry. The registry included DME eyes who received 3 intravitreal anti-VEGF injections (early-switch) or > 3 intravitreal anti-VEGF injections (late-switch) before switching to DEX-i injections. The primary outcome was to estimate the incremental cost needed to obtain a best-corrected visual acuity (BCVA) improvement ≥ 0.1 or a central-retinal thickness CRT ≤ 250 µm. RESULTS: The analysis included 108 eyes, 32 (29.6%) and 76 (70.4%) in the early- and late-switch groups, respectively. Early-switch strategy was associated with a cost saving of €3,057.8; 95% CI: €2,406.4-3,928.4, p < 0.0001). Regarding incremental-cost-effectiveness ratio, late-switch group was associated with an incremental cost of €25,735.2 and €13,533.2 for achieving a BCVA improvement ≥ 0.1 at month 12 and at any of the time-point measured, respectively. At month 12, 38 (35.2%) eyes achieved a BCVA improvement ≥ 0.1. At month 12, 52 (48.1) eyes had achieved a CRT ≤ 250 micron. As compared to baseline, the mean (95% CI) CRT reduction was - 163.1 (- 212.5 to - 113.7) µm and - 161.6 (- 183.8 to - 139.3) µm in the early-switch and late-switch groups, respectively, p = 0.9463. CONCLUSIONS: In DME eyes, who did not adequately respond to anti-VEGF, switching to DEX-i at early stages (after the first 3-monthly injections) was found to be more cost-effective than extending the treatment to 6-monthly injections of anti-VEGF.

Vitamin D in Cancer Prevention: Gaps in Current Knowledge and Room for Hope.

Intensive epigenome and transcriptome analyses have unveiled numerous biological mechanisms, including the regulation of cell differentiation, proliferation, and induced apoptosis in neoplastic cells, as well as the modulation of the antineoplastic action of the immune system, which plausibly explains the observed population-based relationship between low vitamin D status and increased cancer risk. However, large randomized clinical trials involving cholecalciferol supplementation have so far failed to show the potential of such interventions in cancer prevention. In this article, we attempt to reconcile the supposed contradiction of these findings by undertaking a thorough review of the literature, including an assessment of the limitations in the design, conduct, and analysis of the studies conducted thus far. We examine the long-standing dilemma of whether the beneficial effects of vitamin D levels increase significantly above a critical threshold or if the conjecture is valid that an increase in available cholecalciferol translates directly into an increase in calcitriol activity. In addition, we try to shed light on the high interindividual epigenetic and transcriptomic variability in response to cholecalciferol supplementation. Moreover, we critically review the standards of interpretation of the available study results and propose criteria that could allow us to reach sound conclusions in this field. Finally, we advocate for options tailored to individual vitamin D needs, combined with a comprehensive intervention that favors prevention through a healthy environment and responsible health behaviors.

The Economic Burden of Localized Prostate Cancer and Insights Derived from Cost-Effectiveness Studies of the Different Treatments.

Prostate cancer has huge health and societal impacts, and there is no clear consensus on the most effective and efficient treatment strategy for this disease, particularly for localized prostate cancer. We have reviewed the scientific literature describing the economic burden and cost-effectiveness of different treatment strategies for localized prostate cancer in OECD countries. We initially identified 315 articles, studying 13 of them in depth (those that met the inclusion criteria), comparing the social perspectives of cost, time period, geographical area, and severity. The economic burden arising from prostate cancer due to losses in productivity and increased caregiver load is noticeable, but clinical decision-making is carried out with more subjective variability than would be advisable. The direct cost of the intervention was the main driver for the treatment of less severe cases of prostate cancer, whereas for more severe cases, the most important determinant was the loss in productivity. Newer, more affordable radiotherapy strategies may play a crucial role in the future treatment of early prostate cancer. The interpretation of our results depends on conducting thorough sensitivity analyses. This approach may help better understand parameter uncertainty and the methodological choices discussed in health economics studies. Future results of ongoing clinical trials that are considering genetic characteristics in assessing treatment response of patients with localized prostate cancer may shed new light on important clinical and pharmacoeconomic decisions.

Joint association of the Mediterranean diet and smoking with all-cause mortality in the Seguimiento Universidad de Navarra (SUN) cohort.

OBJECTIVES: Although low-quality diets and smoking are independently associated with higher mortality risk, a joint analysis of both risk factors in relation to mortality has not been sufficiently studied. The aim of this study was to explore the effect modification between level of adherence to a Mediterranean dietary pattern (MedDiet) and smoking status on all-cause, cancer, and cardiovascular mortality. METHODS: We conducted a prospective analysis to assess the association between diet and smoking status in the SUN (Seguimiento Universidad de Navarra) cohort study. Deaths were confirmed by review of the National Death Index. Participants were classified into six categories according to the MedDiet (adherence/non-adherence) and their exposure to smoking (never/former/current smoker). Multivariate-adjusted Cox regression models were fitted to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for mortality. During a mean follow-up of 11.5 y (SD 4.5), we observed 18 948 participants (mean age 38.4  y; SD 12.4) and 431 deaths (51.3% cancer deaths). RESULTS: A higher risk for death was found among smokers with a low adherence to the MedDiet (HR, 2.20; 95% CI, 1.45-3.34) compared with never smokers with high adherence to the MedDiet. The P value for supra-multiplicative effect modification was not statistically significant, meaning that the effect of both factors is multiplicative. A higher risk for premature death from cancer was found in smokers and in those non-adherent with the MedDiet. CONCLUSION: Smoking and poor adherence to the MedDiet exerted a multiplicative effect in increasing all-cause mortality and cancer-related mortality in a Spanish population of university graduates.

Fluorescent Flavin/PVP-Coated Silver Nanoparticles: Design and Biological Performance.

A red-emitting fluorescent Riboflavin (RF)/Polyvinylpyrrolidone (PVP)-coated silver nanoparticles system, λem = 527 nm, Φ = 0.242, with a diameter of the metallic core of 27.33 nm and a zeta potential of - 25.05 mV was prepared and investigated regarding its biological activity. We found that PVP has a key role in RF adsorption around the SNPs surface leading to an enhancement of antioxidant properties (∼70%), low cytotoxicity (> 90% cell viability, at 50 µL/mL, after 48 h of incubation) as well as to an efficient process of its cellular uptake (∼ 60%, after 24 h of incubation) in L929 cells. The results are relevant concerning the involvement of RF and its coenzymes forms in SNPs - based systems, in cellular respiration as well as for future studies as antioxidant marker system on tumoral cells for viewing and monitoring them, by cellular imaging.

Concordance between tomographic and surgical AAST injury grades in liver, spleen, and kidney due to blunt abdominal trauma / Concordancia entre los grados de lesión AAST tomográficos y quirúrgicos en hígado, bazo y riñón por trauma cerrado de abdomen

OBJETIVO: Determinar la concordancia entre los grados de lesión de la escala AAST (American Association for the Surgery of Trauma) tomográficos y quirúrgicos en lesiones hepáticas, esplénicas y renales por trauma abdominal cerrado. Método: Estudio prospectivo, unicéntrico, observacional, comparativo y transversal, en pacientes mayores de 15 años con lesión hepática, esplénica o renal por trauma abdominal cerrado, sometidos a tomografía abdominal y posterior laparotomía exploradora, en quienes se determinó la concordancia de los grados de lesión AAST tomográficos y quirúrgicos de estos órganos, de marzo de 2017 a diciembre de 2020, en el Hospital Civil de Culiacán, Sinaloa, México. RESULTADOS: Se incluyeron 48 pacientes, con una edad promedio de 27.9 ± 10.9 años; de ellos, 41 eran hombres (85%). La lesión esplénica fue la más frecuente, en 30 pacientes (63%), seguida de la hepática en 20 (42%) y la renal en 15 (31%). La concordancia del grado de lesión AAST entre la tomografía y la cirugía fue baja o moderada, con valores kappa de 0.234 (p < 0.001), 0.419 (p < 0.001) y 0.415 (p < 0.001) para las lesiones hepáticas, esplénicas y renales, respectivamente. CONCLUSIONES: Los grados de lesión AAST tomográficos y quirúrgicos en el hígado, el bazo y los riñones por trauma abdominal cerrado tienen baja y moderada concordancia, y los grados tomográficos son menores que los quirúrgicos.

Bilateral Choroidal Detachment in the Absence of Previous Intraocular Surgery.

The aim of this report was to present a case of bilateral choroidal detachment following treatment with topical therapy dorzolamide/timolol without history of previous surgery. An 86-year-old woman, with intraocular pressures of 40.00/36.00 mm Hg, was treated with preservative-free double therapy with dorzolamide/timolol. One week later, she presented with bilateral vision loss and irritative symptoms in the face, scalp, and ears, with well controlled pressures. The anterior exam showed LOCS III N4C3 cataracts, and the fundus and ultrasound exams revealed a bilateral infero-temporal choroidal detachment in the absence of neoplasia or other systemic cause. One week in absence of hypotensive treatment and receiving topical prednisolone, she showed reattachment of the choroidal detachment. Six months after cataract surgery, the patient remains stable, without choroidal effusion regression. Hipotensive treatment following chronic angle closure can lead to choroidal effusion similar to cases of acute angle closure treated with oral carbonic-anhydrase inhibitors. The combined strategy of removing hipotensive treatment and topical corticosteroids could be useful for the initial management of choroidal effusion. Also, performing cataract surgery after choroidal reattachment can help with stabilization.