Patterns of Progression of Nonproliferative Diabetic Retinopathy Using Non-Invasive Imaging.

Purpose: To identify progression of nonproliferative diabetic retinopathy (NPDR) in patients with type 2 diabetes by combining optical coherence tomography angiography (OCTA) metrics and color fundus photography (CFP) images. Methods: This study was a post hoc analysis of a prospective longitudinal cohort study (CORDIS, NCT03696810) with 2-year duration. This study enrolled 122 eyes. Ophthalmological examinations included OCTA and CFP. OCTA metrics included skeletonized vessel density (SVD) and perfusion density (PD) at the superficial capillary plexus (SCP) and deep capillary plexus (DCP). Microaneurysm turnover analysis and Early Treatment Diabetic Retinopathy Study (ETDRS) grading for diabetic retinopathy (DR) severity assessment were performed on 7-field CFP. Results: Eyes graded as ETDRS level 20 showed significant capillary nonperfusion predominantly in the inner ring area in the SCP (P < 0.001), whereas eyes graded as ETDRS level 35 and ETDRS levels 43 and 47 showed significant capillary nonperfusion in both the SCP and DCP in both inner and outer rings (P < 0.001). When evaluating rates of progression in capillary nonperfusion for the 2-year period of follow-up, changes were found predominantly in the DCP for SVD and PD and were better identified in the outer ring area. Microaneurysm turnover contributes to the characterization of NPDR progression by discriminating ETDRS level 35 from ETDRS levels 43 and 47 (P < 0.001), which could not be achieved using only OCTA metrics. Conclusions: Patterns of progression of NPDR can be identified combining OCTA examinations of the superficial and deep retinal capillary plexi of central retina and determination of microaneurysm turnover from fundus photographs. Translational Relevance: Our study reports results from a registered clinical trial that advances understanding of disease progression in NPDR.

Characterization of central-involved diabetic macular edema using OCT and OCTA.

PURPOSE: To characterize the occurrence of diabetic macular edema and the presence of abnormal retinal fluid accumulation in nonproliferative diabetic retinopathy (NPDR). METHODS: In this two-year prospective study, a total of 122 eyes with diabetes type 2 underwent optical coherence tomography (OCT) and OCT-Angiography in association with OCT-Fluid imaging, a novel algorithm of OCT analysis allowing quantification of abnormal accumulation of fluid in the retina through low optical reflectivity ratios (LOR). Early Treatment Diabetic Retinopathy Study (ETDRS) grading for diabetic retinopathy (DR) severity assessment was performed using 7-field color fundus photography. Best corrected visual acuity was also recorded. RESULTS: During the 2-year follow-up, 23 eyes (19%) developed central-involved diabetic macular edema (CI-DME) and 2 eyes (2%) developed clinically significant macular edema (CSME). In the two-year period of the study, eyes that developed CI-DME showed a progressive increase in central retinal thickness (CRT) (ß = 7.7 ± 2.1 µm/year, p < 0.001) and in LOR values (ß = 0.009 ± 0.004 ratio/year, p = 0.027). The increase in CRT and abnormal retinal fluid, represented by increased LOR ratios, are associated with increased retinal perfusion in the deep capillary plexus (DCP) (skeletonized vessel density, p = 0.039). In contrast, the eyes with CSME showed decreased retinal perfusion and abnormal fluid located in the outer layers of the retina. CONCLUSIONS: CI-DME and CSME appear to represent different entities. Eyes with CI-DME show increases in abnormal retinal fluid associated with increased retinal vascular perfusion in the DCP. Eyes with CSME are apparently associated with decreased retinal vascular perfusion in the DCP and abnormal fluid in the outer retina.

Comparison of diuretics and fluid expansion in the initial treatment of patients with normotensive acute pulmonary embolism: a systematic review and meta-analysis.

BACKGROUND: Right ventricular (RV) dysfunction is the main cause of death in patients with normotensive acute pulmonary embolism (PE). The optimal management for this subset of patients remains uncertain. This systematic review and meta-analysis focused on the comparison of diuretics and fluid expansion in patients with acute PE presenting with RV dysfunction and haemodynamic stability. METHODS: A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines considering only RTCs. The authors searched the traditional and grey literature through 1 November 2022. Meta-analysis used open source packages in R. Inverse variance fixed-effects models with OR as the effect measure were used for primary analyses. The main outcomes defined in this review protocol included pulmonary arterial systolic pressure (PASP), creatinine value changes and N-terminal pro-B-type natriuretic peptide during the first 24 hours. RESULTS: Four studies with a total of 452 patients met the inclusion criteria. The baseline characteristics of patients were similar across all studies. Overall, patients receiving diuretics had a significant 24 hours reduction in pro-B-type natriuretic peptide (standard mean difference of -41.97; 95% CI -65.79 to -18.15), and PASP (standard mean difference of -5.96; 95% CI -8.06 to -3.86). This group had significantly higher creatinine levels (standard mean difference of 7.74; 95% CI 5.04 to 10.45). The quality of the studies was heterogeneous; two had a low risk of bias, and the other two had a high risk of bias. CONCLUSIONS: Very few studies have compared the efficacy and safety of diuretics and fluid expansion in normotensive patients with acute PE with RV failure. Overall, furosemide appears to reduce RV dysfunction in this subset of patients compared with fluid expansion. Further research is required to confirm these findings.

CENTRAL AND PERIPHERAL INVOLVEMENT OF THE RETINA IN THE INITIAL STAGES OF DIABETIC RETINOPATHY.

PURPOSE: To determine the degree of central microvascular closure using optical coherence tomography angiography in eyes of patients with type 2 diabetes with visible lesions only in the central retina or only in the periphery. METHODS: Cross-sectional study. All 127 eyes underwent ultra-widefield fundus photography 200° examinations with OPTOS California (Optos, Dunfermline, United Kingdom) and Cirrus Angioplex optical coherence tomography angiography 3 × 3 mm acquisitions (ZEISS, Dublin, CA). RESULTS: Twenty-five eyes showed visible lesions only in the central retina, 57 only in the peripheral retina, and 45 presented visible lesions in entire retina. The group with visible lesions only in the periphery showed definite closure in the superficial capillary plexus in 49% of the eyes, whereas the group with visible lesions only in the central seven-early treatment diabetic retinopathy study fields area showed a definite closure in 64%. CONCLUSION: Central capillary closure is already present in the initial stages of diabetic retinopathy even when lesions are only visible in the peripheral retina. Capillary closure in the superficial capillary plexus is three times more frequent than in the deep capillary plexus, demonstrating earlier closure of the superficial capillary plexus. Eyes with visible lesions only in the periphery show a milder form of retinopathy.

Associations of medicine use and ejection fraction with the coexistence of frailty and sarcopenia in a sample of heart failure outpatients: a cross-sectional study.

BACKGROUND: Frailty and sarcopenia have been extensively studied in heart failure (HF) patients, but their coexistence is unknown. The aim of this work is to describe the coexistence of these conditions in a sample of HF outpatients and its association with the use of medication and left-ventricular ejection fraction. METHODS: Participants in this cross-sectional study were recruited from a HF outpatients' clinic in northern Portugal. Frailty phenotype was assessed according to Fried et al. Sarcopenia was evaluated according to the revised consensus of the European Working Group on Sarcopenia in Older People. RESULTS: A total of 136 HF outpatients (33.8% women, median age 59 years) integrated this study. Frailty and sarcopenia accounted for 15.4% and 18.4% of the sample, respectively. Coexistence of frailty and sarcopenia was found in 8.1% of the participants, while 17.6% had only one of the conditions. In multivariable analysis (n = 132), increasing age (OR = 1.13;95%CI = 1.06,1.20), being a woman (OR = 65.65;95%CI = 13.50, 319.15), having heart failure with preserved ejection fraction (HFpEF) (OR = 5.61; 95%CI = 1.22, 25.76), and using antidepressants (OR = 11.05; 95%CI = 2.50, 48.82), anticoagulants (OR = 6.11; 95%CI = 1.69, 22.07), furosemide (OR = 3.95; 95%CI = 1.07, 14.55), and acetylsalicylic acid (OR = 5.01; 95%CI = 1.10, 22.90) were associated with increased likelihood of having coexistence of frailty and sarcopenia, while using statins showed the inverse effect (OR = 0.06; 95%CI = 0.01, 0.30). CONCLUSIONS: The relatively low frequency of coexistence of frailty and sarcopenia signifies that each of these two conditions still deserve individual attention from health professionals in their clinical practice and should be screened separately. Being a woman, older age, having HFpEF, using anticoagulants, antidepressants, loop diuretics and acetylsalicylic acid, and not using statins, were associated with having concomitant frailty and sarcopenia. These patients can potentially benefit from interventions that impact their quality of life such as nutritional and mental health interventions and exercise training.

Retinal neurodegeneration in eyes with NPDR risk phenotypes: A two-year longitudinal study.

INTRODUCTION: Diabetic retinopathy (DR) is both a microangiopathy and a neurodegenerative disease. However, the connections between both changes are not well known. PURPOSE: To characterise the longitudinal retinal ganglion cell layer + inner plexiform layer (GCL + IPL) changes and their association with microvascular changes in type-2 diabetes (T2D) patients with nonproliferative diabetic retinopathy (NPDR). METHODS: This two-year prospective study (CORDIS, NCT03696810) included 122 T2D individuals with NPDR identified as risk phenotypes B and C, which present a more rapid progression. Phenotype C was identified by decreased VD ≥ 2SD in healthy controls, and phenotype B, identified by subclinical macular oedema with only minimal vascular closure. The GCL + IPL thickness, vessel density, perfusion density and area of intercapillary spaces (AIS) were assessed by optical coherence tomography (OCT) and OCT angiography (OCTA). Linear mixed effects models were employed to evaluate the retinal GCL + IPL progression and its associations. RESULTS: Regarding GCL + IPL thickness, T2D individuals presented on average 80.1 ± 7.49 µm, statistically significantly lower than the healthy control group, 82.5 ± 5.71 (p = 0.022), with only phenotype C differing significantly from controls (p = 0.006). GCL + IPL thickness steadily decreased during the two-year period in both risk phenotypes, with an annual decline rate of -0.372 µm/year (p < 0.001). Indeed, phenotype C showed a higher rate of progression (-0.459 µm/year, p < 0.001) when compared to phenotype B (-0.296 µm/year, p = 0.036). Eyes with ETDRS grade 20 showed GCL + IPL thickness values comparable to those of healthy control group (83.3 ± 5.80 and 82.7 ± 5.50 µm, respectively, p = 0.880), whereas there was a progressive decrease in GCL + IPL thickness in ETDRS grades 35 and 43-47 associated with the increase in severity of the retinopathy (-0.276 µm/year, p = 0.004; -0.585 µm/year, p = 0.013, respectively). Furthermore, the study showed statistically significant associations between the progressive thinning of GCL + IPL and the progressive increase in retinal capillary non-perfusion, with particular relevance for AIS (p < 0.001). CONCLUSIONS: Our findings showed that, in eyes with NPDR and at risk for progression, retinal neurodegeneration occurs at different rates in different risk phenotypes, and it is associated with retinal microvascular non-perfusion.

Retinal Capillary Nonperfusion in Preclinical Diabetic Retinopathy.

INTRODUCTION: The aim of the study was to identify retinal microvascular changes using optical coherence tomography angiography (OCTA) in type 2 diabetes (T2D) patients with preclinical retinopathy identified by ultra-widefield fundus photography (UWF-FP). METHODS: This is a cross-sectional observational study. All patients underwent UWF-FP 200° examinations with OPTOS California (Optos, Dunfermline, UK) and Cirrus AngioPlex® spectral-domain (SD)-OCTA 3 × 3 mm acquisitions (ZEISS, Dublin, CA, USA). The absence of visible lesions was identified using UWF-FP. RESULTS: One hundred and ninety three eyes of individuals with T2D with no visible lesions in the fundus and identified in a screening setting were included in the study. Skeletonized vessel density (SVD), perfusion density (PD), and areas of capillary nonperfusion (CNP) values on SD-OCTA were significantly decreased when compared with healthy population (p < 0.001). SVD and CNP values of the superficial capillary plexus (SCP) were more frequently decreased (35% and 45%, respectively) than SVD values of the deep capillary plexus (DCP) (9% and 15%, respectively), demonstrating that diabetic microvascular changes occur earlier in the SCP than in the DCP. The ischemic phenotype, identified by a definite decrease in SVD or CNP in the SCP may, therefore, be identified in the preclinical stage of diabetic retinal disease. CONCLUSIONS: Retinal capillary nonperfusion detected by OCTA metrics of SVD and CNP can be identified in the central retina in eyes with T2D before development of visible lesions in the retina. Our findings confirm the relevance of OCTA to identify macular microvascular changes in the initial stages of diabetic retinopathy, allowing the identification of its ischemic phenotype very early in the disease process.

Medicinal Plants, Phytochemicals and Regulation of the NLRP3 Inflammasome in Inflammatory Bowel Diseases: A Comprehensive Review.

Ongoing research explores the underlying causes of ulcerative colitis and Crohn's disease. Many experts suggest that dysbiosis in the gut microbiota and genetic, immunological, and environmental factors play significant roles. The term "microbiota" pertains to the collective community of microorganisms, including bacteria, viruses, and fungi, that reside within the gastrointestinal tract, with a particular emphasis on the colon. When there is an imbalance or disruption in the composition of the gut microbiota, it is referred to as dysbiosis. Dysbiosis can trigger inflammation in the intestinal cells and disrupt the innate immune system, leading to oxidative stress, redox signaling, electrophilic stress, and inflammation. The Nod-like Receptor (NLR) Family Pyrin Domain Containing 3 (NLRP3) inflammasome, a key regulator found in immunological and epithelial cells, is crucial in inducing inflammatory diseases, promoting immune responses to the gut microbiota, and regulating the integrity of the intestinal epithelium. Its downstream effectors include caspase-1 and interleukin (IL)-1ß. The present study investigated the therapeutic potential of 13 medicinal plants, such as Litsea cubeba, Artemisia anomala, Piper nigrum, Morus macroura, and Agrimonia pilosa, and 29 phytocompounds such as artemisitene, morroniside, protopine, ferulic acid, quercetin, picroside II, and hydroxytyrosol on in vitro and in vivo models of inflammatory bowel diseases (IBD), with a focus on their effects on the NLRP3 inflammasome. The observed effects of these treatments included reductions in IL-1ß, tumor necrosis factor-alpha, IL-6, interferon-gamma, and caspase levels, and increased expression of antioxidant enzymes, IL-4, and IL-10, as well as regulation of gut microbiota. These effects could potentially provide substantial advantages in treating IBD with few or no adverse effects as caused by synthetic anti-inflammatory and immunomodulated drugs. However, additional research is necessary to validate these findings clinically and to develop effective treatments that can benefit individuals who suffer from these diseases.

Polyketide Synthase-Mediated O-Methyloxime Formation in the Biosynthesis of the Oximidine Anticancer Agents.

Bacterial trans-acyltransferase polyketide synthases (trans-AT PKSs) are modular megaenzymes that employ unusual catalytic domains to assemble diverse bioactive natural products. One such PKS is responsible for the biosynthesis of the oximidine anticancer agents, oxime-substituted benzolactone enamides that inhibit vacuolar H+ -ATPases. Here, we describe the identification of the oximidine gene cluster in Pseudomonas baetica and the characterization of four novel oximidine variants, including a structurally simpler intermediate that retains potent anticancer activity. Using a combination of in vivo, in vitro and computational approaches, we experimentally elucidate the oximidine biosynthetic pathway and reveal an unprecedented mechanism for O-methyloxime formation. We show that this process involves a specialized monooxygenase and methyltransferase domain and provide insight into their activity, mechanism and specificity. Our findings expand the catalytic capabilities of trans-AT PKSs and identify potential strategies for the production of novel oximidine analogues.

Optical coherence microscopy with a split-spectrum image reconstruction method for temporal-dynamics contrast-based imaging of intracellular motility.

Biomedical researchers use optical coherence microscopy (OCM) for its high resolution in real-time label-free tomographic imaging. However, OCM lacks bioactivity-related functional contrast. We developed an OCM system that can measure changes in intracellular motility (indicating cellular process states) via pixel-wise calculations of intensity fluctuations from metabolic activity of intracellular components. To reduce image noise, the source spectrum is split into five using Gaussian windows with 50% of the full bandwidth. The technique verified that F-actin fiber inhibition by Y-27632 reduces intracellular motility. This finding could be used to search for other intracellular-motility-associated therapeutic strategies for cardiovascular diseases.

Phytochemicals and Regulation of NF-kB in Inflammatory Bowel Diseases: An Overview of In Vitro and In Vivo Effects.

Inflammatory bowel diseases (IBD) are chronic relapsing idiopathic inflammatory conditions affecting the gastrointestinal tract. They are mainly represented by two forms, ulcerative colitis (UC) and Crohn's disease (CD). IBD can be associated with the activation of nuclear factors, such as nuclear factor-kB (NF-kB), leading to increased transcription of pro-inflammatory mediators that result in diarrhea, abdominal pain, bleeding, and many extra-intestinal manifestations. Phytochemicals can interfere with many inflammation targets, including NF-kB pathways. Thus, this review aimed to investigate the effects of different phytochemicals in the NF-kB pathways in vitro and in vivo models of IBD. Fifty-six phytochemicals were included in this study, such as curcumin, resveratrol, kaempferol, sesamol, pinocembrin, astragalin, oxyberberine, berberine hydrochloride, botulin, taxifolin, naringin, thymol, isobavachalcone, lancemaside A, aesculin, tetrandrine, Ginsenoside Rk3, mangiferin, diosgenin, theanine, tryptanthrin, lycopene, gyngerol, alantolactone, mangostin, ophiopogonin D, fisetin, sinomenine, piperine, oxymatrine, euphol, artesunate, galangin, and nobiletin. The main observed effects related to NF-kB pathways were reductions in tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1ß, IL-6, interferon-gamma (IFN-γ), and cyclooxygenase-2 (COX-2), and augmented occludin, claudin-1, zonula occludens-1, and IL-10 expression levels. Moreover, phytochemicals can improve weight loss, stool consistency, and rectal bleeding in IBD. Therefore, phytochemicals can constitute a powerful treatment option for IBD in humans.

Characterisation of progression of macular oedema in the initial stages of diabetic retinopathy: a 3-year longitudinal study.

BACKGROUND/OBJECTIVES: To characterise the prevalence and three-year progression of centre-involving diabetic macular oedema (CI-DMO) in minimal to moderate non-proliferative diabetic retinopathy, using optical coherence tomography (OCT) and measurements of retinal fluid using tissue optical reflectivity ratios (OCT-Leakage). METHODS/METHODS: Seventy-four eyes from 74 patients were followed in a 3-year prospective longitudinal observational cohort of type 2 diabetes (T2D) patients using spectral-domain optical coherence tomography (SD-OCT), OCT-Angiography (OCT-A) and OCT-Leakage (OCT-L). Eyes were examined four times with 1-year intervals. Sixteen eyes (17.8%) were excluded from the analysis due to quality control standards. Retinal oedema was measured by central retinal thickness and retinal fluid by using optical reflectivity ratios obtained with the OCT-L algorithm. Vessel density was measured by OCT-A. Thinning of the ganglion cell and inner plexiform layers (GCL + IPL) was examined to identify retinal neurodegenerative changes. Diabetic retinopathy ETDRS classification was performed using the seven-field ETDRS protocol. RESULTS: CI-DMO was identified in the first visit in 9% of eyes in ETDRS groups 10-20, 10% of eyes in ETDRS group 35 and 15% of eyes in ETDRS groups 43-47. The eyes with CI-DMO and subclinical CI-DMO showed a progressive increase in retinal extracellular fluid during the 3-year period of follow-up. The eyes with CI-DMO and increased retinal extracellular fluid accumulation were associated with vision loss. CONCLUSIONS: The prevalence of subclinical CI-DMO and CI-DMO in the initial stages of NPDR occurs independently of severity grading of the retinopathy, showing progressive increase in retinal extracellular fluid and this increase is associated with vision loss (82% 9 out of 11 cases).

Efficacy Evaluation of SDF-1α-Based Polypeptides in an Acute Myocardial Infarction Model Using Structure-Based Drug Design.

Stromal cell-derived factor-1 alpha (SDF-1α, CXCL12) mediates the migration of circulating cells to desired sites for tissue development, homeostasis, and regeneration and can be used to promote cardiac regeneration by recruiting stem cells. However, the use of SDF-1α in the injured heart necessitates not only higher binding affinity to its receptor, CXCR4+, but also better robustness against enzymatic degradation than other SDF-1 isoforms. Here, we conduct a screening of SDF-1α analog peptides that were designed by structure-based drug design (SBDD), a type of computer-aided drug design (CADD). We have developed in vitro and in vivo methods that enable us to estimate the effect of peptides on the migration of human mesenchymal stem cells (hMSCs) and cardiac regeneration in acute myocardial infarction (AMI)-induced animals, respectively. We demonstrate that one type of SDF-1α analog peptide, SDP-4, among the four analog peptides preselected by SBDD, is more potent than native SDF-1α for cardiac regeneration in myocardial infarction. It is interesting to note that the migratory effects of SDP-4 determined by a wound healing assay, a Transwell assay, and a 2D migration assay are comparable to those of SDF-1α. These results suggest that in vivo, as well as in vitro, screening of peptides developed by SBDD is a quintessential process to the development of a novel therapeutic compound for cardiac regeneration. Our finding also has an implication that the SDP-4 peptide is an excellent candidate for use in the regeneration of an AMI heart.

Mycotoxins Contamination in Rice: Analytical Methods, Occurrence and Detoxification Strategies.

The prevalence of mycotoxins in the environment is associated with potential crop contamination, which results in an unavoidable increase in human exposure. Rice, being the second most consumed cereal worldwide, constitutes an important source of potential contamination by mycotoxins. Due to the increasing number of notifications reported, and the occurrence of mycotoxins at levels above the legislated limits, this work intends to compile the most relevant studies and review the main methods used in the detection and quantification of these compounds in rice. The aflatoxins and ochratoxin A are the predominant mycotoxins detected in rice grain and these data reveal the importance of adopting safety storage practices that prevent the growth of producing fungi from the Aspergillus genus along all the rice chain. Immunoaffinity columns (IAC) and QuECHERS are the preferred methods for extraction and purification and HPLC-MS/MS is preferred for quantification purposes. Further investigation is still required to establish the real exposition of these contaminants, as well as the consequences and possible synergistic effects due to the co-occurrence of mycotoxins and also for emergent and masked mycotoxins.

Statins are associated with reduced likelihood of sarcopenia in a sample of heart failure outpatients: a cross-sectional study.

BACKGROUND: Sarcopenia is prevalent in heart failure (HF) patients, contributing to its poor prognosis. Statin use is postulated as a probable risk for developing sarcopenia, but little is known regarding this association in HF patients. This work aims at classifying and characterising sarcopenia and at describing the association of statin use with sarcopenia in a sample of Portuguese HF outpatients. METHODS: In this cross-sectional study, a sample of 136 HF patients (median age: 59 years, 33.8% women) was recruited from an HF outpatients' clinic of a University Hospital in Portugal. Sarcopenia was defined according to the European Working Group on Sarcopenia in Older People 2. Clinical, nutritional, and dietary data were collected. RESULTS: A total of 25 (18.4%) individuals were categorised as sarcopenic, ranging from 12.2% in younger (< 65 years) participants vs. 30.4% in older ones and from 3.3% in men vs. 47.8% in women. Severe sarcopenia accounted for 7.4% of the sample and sarcopenic obesity was identified in 5.1% of the individuals. A total of 65.4% of the participants were statin users. In multivariable analysis (n = 132, 25 sarcopenic), the use of statins was inversely associated with sarcopenia (OR = 0.03; 95% CI = 0.01, 0.30). Each additional age year was associated with a 9% increase in the likelihood of being sarcopenic (OR = 1.09; 95% CI = 1.01, 1.17), and each Kg.m-2 increment in body mass index was associated with a 21% decrease in the likelihood of sarcopenia (OR = 0.79; 95% CI = 0.65, 0.96). The daily use of five or more medicines was also directly associated with sarcopenia (OR = 26.87; 95% CI = 2.01, 359.26). On the other hand, being a man and being physically active were inversely associated with sarcopenia (OR = 0.01; 95% CI = 0.00, 0.07 and OR = 0.09; 95% CI = 0.01, 0.65, respectively). CONCLUSIONS: Contrary to what was expected, patients medicated with statins were less likely to be sarcopenic. Although this finding deserves further research, we hypothesise that this might be related to the pleiotropic effects of statins on endothelial function, contributing to better neuromuscular fitness.

DESCENDING NECROTIZING MEDIASTINITIS - A MULTIDISCIPLINARY PATHOLOGY.

A 23-year-old man presented with fever and cervical swelling. Contrast-enhanced CT-scan with oblique sagittal planes reconstructions with extensive collection with gaseous areas, involving multiple cervical and mediastinal spaces is shown, reflecting a cervical-mediastinal necrotizing fasciitis. Note the circumference to the laryngotracheal axis. He underwent combined surgery by ENT and thoracic surgery and was discharged without sequelae after long hospitalization. This case demonstrates the importance of working in a multidisci- plinary team to treat complex pathologies.

Panax ginseng and aging related disorders: A systematic review.

The aging process predisposes numerous homeostatic disorders, metabolic disorders, cardiovascular diseases, neurodegenerative diseases, and cancer. Changes in diet and lifestyle and therapeutic adjuvants are essential to minimize the effects of comorbidities associated with aging. Natural products such as Panax ginseng have been used to treat and prevent diseases related to aging. This review aims to investigate the effects of Panax ginseng in various conditions associated with aging, such as inflammation, oxidative stress, mitochondrial dysfunction, apoptosis, neurodegenerative and metabolic disorders, cardiovascular diseases, and cancer. The ginsenosides, chemical constituents found in Panax ginseng, can inhibit the effects of inflammatory cytokines, inhibit signaling pathways that induce inflammation, and inhibit cells that participate in inflammatory processes. Besides, ginsenosides are involved in neuroprotective effects on the central nervous system due to anti-apoptotic, antioxidant, and anti-inflammatory effects. The use of ginseng extract showed actions on lipid homeostasis, positively regulating high-density lipoprotein, down-regulating low-density lipoprotein and triglyceride levels, and producing beneficial effects on vascular endothelial function. The use of this plant in cancer resulted in improved quality of life and mood. It decreased symptoms of fatigue, nausea, vomiting, and dyspnea, reducing anxiety. Panax ginseng has been shown to exert potent therapeutic benefits that can act as a complementary treatment in managing patients with chronic diseases related to aging.

Preliminary findings on the gastrointestinal parasites of the brown bear (Ursus arctos) in the Cantabrian mountains, Spain.

No study is currently available on the parasitofauna of the population of brown bears (Ursus arctos) inhabiting the Cantabrian Mountains in Spain. The aim of the present study was to obtain novel information on diversity and prevalence of gastrointestinal parasites in these individuals. During August 2016 and from May to July 2017, 14 fecal samples were collected from the western Cantabrian bear subpopulation, in the Somiedo Natural Park, in the Spanish province of Asturias. The prevalence of parasites detected was 71% and two genera were identified: Dicrocoelium sp. and Trichuris sp. Since the impact that pathogens such as endoparasites can have on the health of bears, together with other stressors, is still poorly understood, research efforts that include disease surveillance are critical to the successful protection of this emblematic species. Our preliminary findings require further investigations, with a wider sampling effort, and bring awareness for the need of carrying further studies on this area as a part of a proactive species management plan.

Association between Neurodegeneration and Macular Perfusion in the Progression of Diabetic Retinopathy: A 3-Year Longitudinal Study.

OBJECTIVE AND PURPOSE: The aim of this study was to explore the relation between retinal neurodegenerative changes and vessel closure (VC) in individuals with nonproliferative diabetic retinopathy (NPDR) in a follow-up period of 3 years. DESIGN: This is a 3-year prospective longitudinal study with four annual visits. PARTICIPANTS: This study involved 74 individuals with type 2 diabetes, NPDR, and Early Treatment Diabetic Retinopathy Study grades from 10 to 47, one eye/person. An age-matched healthy control population of 84 eyes was used as control group. METHODS: Participants were annually examined by color fundus photography, spectral domain-optical coherence tomography (SD-OCT) and OCT-angiography (OCTA). VC was assessed by OCTA vessel density maps. SD-OCT segmentations were performed to access central retinal thickness (CRT) and retinal neurodegeneration considered as thinning of the ganglion cell plus inner plexiform layer (GCL + IPL). RESULTS: Type 2 diabetic individuals presented significantly higher CRT (p = 0.001), GCL + IPL thinning (p = 0.042), and decreased vessel density at the superficial capillary plexus (p < 0.001) and full retina (FR) (p = 0.001). When looking at changes occurring over the 3-year period of follow-up (Table 2), there were statistically significant decreases in GCL + IPL thickness (-0.438 µm/year; p = 0.038), foveal avascular zone circularity (-0.009; p = 0.047), and vessel density in superficial capillary plexus (-0.172 mm-1/year; p < 0.001), deep capillary plexus (DCP) (-0.350 mm-1/year; p < 0.001), and FR (-0.182 mm-1/year; p < 0.001). A statistically significant association was identified between GCL + IPL thinning and decrease in DCP vessel density (ß = 0.196 [95% confidence interval: 0.037, 0.355], z = 2.410, p = 0.016), after controlling for age, gender, diabetes duration, hemoglobin A1c level, and CRT. CONCLUSIONS: Retinal neurodegenerative changes show a steady progression during a 3-year period of follow-up in eyes with NPDR and appear to be directly associated with progression in decreased vessel density including vascular closure through preferential involvement of the DCP. Our findings provide evidence that retinal neuropathy is linked with microvascular changes occurring in diabetic patients.

Relationship of Inflammatory Markers and Metabolic Syndrome in Postmenopausal Women.

The increased deposition of visceral fat in the postmenopause period increases the production of inflammatory cytokines and the release of tumor necrosis factor- α (TNF-α), interleukin-6 (IL-6), and decrease in IL-10. This study investigated the relationship between inflammatory biomarkers and metabolic syndrome (MS) in postmenopausal women considering different diagnostic criteria. We conducted a cross-sectional observational study based on STROBE. Data were collected regarding the diagnostic criteria for MS (International Diabetes Federation; NCEP (International Diabetes Federation (IDF), National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP-III), and Harmonized criteria), body composition, comorbidities, time without menstruation, values of IL-6, IL-10, and TNF-α. ANOVA, Kruskal-Wallis, Levene tests, ROC, and odds ratio were performed to analyze the data. The results showed no significant difference between the methods and no interaction between the method and the presence of MS. However, for the values of WC, body fat percentage, TNF-α, and IL-10/TNF-α ratio, a significant effect of MS was observed. In subjects with MS, lower values of body fat percentage and TNF-α and higher values of the IL-10/TNF-α ratio were also observed. The higher IL-10/TNF-α ratio in the MS group is related to the greater anti-inflationary action of IL-10. The IL-10/TNF-α ratio showed significant accuracy to discriminate patients with MS according to the NCEP-ATP III criteria.