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Purpose: To evaluate and compare the effectiveness of nearest neighbor (NN)- and variational autoencoder (VAE)-smoothing algorithms to reduce variability and enhance the performance of glaucoma visual field (VF) progression models. Design: Longitudinal cohort study. Subjects: 7150 eyes (4232 patients), with ≥ 5 years of follow-up and ≥ 6 visits. Methods: Vsual field thresholds were smoothed with the NN and VAE algorithms. The mean total deviation (mTD) and VF index rates, pointwise linear regression (PLR), permutation of PLR (PoPLR), and the glaucoma rate index were applied to the unsmoothed and smoothed data. Main Outcome Measures: The proportion of progressing eyes and the conversion to progression were compared between the smoothed and unsmoothed data. A simulation series of noiseless VFs with various patterns of glaucoma damage was used to evaluate the specificity of the smoothing models. Results: The mean values of age and follow-up time were 62.8 (standard deviation: 12.6) years and 10.4 (standard deviation: 4.7) years, respectively. The proportion of progression was significantly higher for the NN and VAE smoothed data compared with the unsmoothed data. VF progression occurred significantly earlier with both smoothed data compared with unsmoothed data based on mTD rates, PLR, and PoPLR methods. The ability to detect the progressing eyes was similar for the unsmoothed and smoothed data in the simulation data. Conclusions: Smoothing VF data with NN and VAE algorithms improves the signal-to-noise ratio for detection of change, results in earlier detection of VF progression, and could help monitor glaucoma progression more effectively in the clinical setting. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Purpose: To report an image analysis pipeline, DDLSNet, consisting of a rim segmentation (RimNet) branch and a disc size classification (DiscNet) branch to automate estimation of the disc damage likelihood scale (DDLS). Design: Retrospective observational. Participants: RimNet and DiscNet were developed with 1208 and 11 536 optic disc photographs (ODPs), respectively. DDLSNet performance was evaluated on 120 ODPs from the RimNet test set, for which the DDLS scores were graded by clinicians. Reproducibility was evaluated on a group of 781 eyes, each with 2 ODPs taken within 4 years apart. Methods: Disc damage likelihood scale calculation requires estimation of optic disc size, provided by DiscNet (VGG19 network), and the minimum rim-to-disc ratio (mRDR) or absent rim width (ARW), provided by RimNet (InceptionV3/LinkNet segmentation model). To build RimNet’s dataset, glaucoma specialists marked optic disc rim and cup boundaries on ODPs. The ''ground truth'' mRDR or ARW was calculated. For DiscNet’s dataset, corresponding OCT images provided ''ground truth'' disc size. Optic disc photographs were split into 80/10/10 for training, validation, and testing, respectively, for RimNet and DiscNet. DDLSNet estimation was tested against manual grading of DDLS by clinicians with the average score used as ''ground truth.'' Reproducibility of DDLSNet grading was evaluated by repeating DDLS estimation on a dataset of nonprogressing paired ODPs taken at separate times. Main Outcome Measures: The main outcome measure was a weighted kappa score between clinicians and the DDLSNet pipeline with agreement defined as ± 1 DDLS score difference. Results: RimNet achieved an mRDR mean absolute error (MAE) of 0.04 (± 0.03) and an ARW MAE of 48.9 (± 35.9) degrees when compared to clinician segmentations. DiscNet achieved 73% (95% confidence interval [CI]: 70%, 75%) classification accuracy. DDLSNet achieved an average weighted kappa agreement of 0.54 (95% CI: 0.40, 0.68) compared to clinicians. Average interclinician agreement was 0.52 (95% CI: 0.49, 0.56). Reproducibility testing demonstrated that 96% of ODP pairs had a difference of ≤ 1 DDLS score. Conclusions: DDLSNet achieved moderate agreement with clinicians for DDLS grading. This novel approach illustrates the feasibility of automated ODP grading for assessing glaucoma severity. Further improvements may be achieved by increasing the number of incomplete rims sample size, expanding the hyperparameter search, and increasing the agreement of clinicians grading ODPs. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Purpose: Accurate neural rim measurement based on optic disc imaging is important to glaucoma severity grading and often performed by trained glaucoma specialists. We aim to improve upon existing automated tools by building a fully automated system (RimNet) for direct rim identification in glaucomatous eyes and measurement of the minimum rim-to-disc ratio (mRDR) in intact rims, the angle of absent rim width (ARW) in incomplete rims, and the rim-to-disc-area ratio (RDAR) with the goal of optic disc damage grading. Design: Retrospective cross sectional study. Participants: One thousand and twenty-eight optic disc photographs with evidence of glaucomatous optic nerve damage from 1021 eyes of 903 patients with any form of primary glaucoma were included. The mean age was 63.7 (± 14.9) yrs. The average mean deviation of visual fields was −8.03 (± 8.59). Methods: The images were required to be of adequate quality, have signs of glaucomatous damage, and be free of significant concurrent pathology as independently determined by glaucoma specialists. Rim and optic cup masks for each image were manually delineated by glaucoma specialists. The database was randomly split into 80/10/10 for training, validation, and testing, respectively. RimNet consists of a deep learning rim and cup segmentation model, a computer vision mRDR measurement tool for intact rims, and an ARW measurement tool for incomplete rims. The mRDR is calculated at the thinnest rim section while ARW is calculated in regions of total rim loss. The RDAR was also calculated. Evaluation on the Drishti-GS dataset provided external validation (Sivaswamy 2015). Main Outcome Measures: Median Absolute Error (MAE) between glaucoma specialists and RimNet for mRDR and ARW. Results: On the test set, RimNet achieved a mRDR MAE of 0.03 (0.05), ARW MAE of 31 (89)°, and an RDAR MAE of 0.09 (0.10). On the Drishti-GS dataset, an mRDR MAE of 0.03 (0.04) and an mRDAR MAE of 0.09 (0.10) was observed. Conclusions: RimNet demonstrated acceptably accurate rim segmentation and mRDR and ARW measurements. The fully automated algorithm presented here would be a valuable component in an automated mRDR-based glaucoma grading system. Further improvements could be made by improving identification and segmentation performance on incomplete rims and expanding the number and variety of glaucomatous training images.

The family of pro-inflammatory and pro-angiogenic chemokines including Interleukin-8 (IL-8, aka CXCL8) and its homologues (CXCL1,2,3,5,6, and 7) exhibit promiscuous binding and activation of several G-protein-coupled receptors (i.e., CXCR2, CXCR1, and the atypical chemokine receptor (ACKR1)). A high proportion of their biological activity is attributed to CXCR2 activation, thus many CXCR2 inhibitors are in clinical trials for several chronic diseases. However, CXCR2 inhibition is often only investigated acutely in these trials or in Cxcr2 -/- mice grown in gnotobiotic conditions. Since humans do not live in germ-free environments, our first goal is to highlight novel retinal and systemic observations in Cxcr2 -/- mice grown in non-gnotobiotic conditions that suggest potential harmful consequences of long-term CXCR2 deficiency or blockade. Beyond confirmation of circulating blood/immune cell-related phenotypes, we report novel findings in Cxcr2 -/- mice including: (1) delayed dye transit to the retinal vasculature, (2) alterations in the density and distribution of retinal vessels, astrocytes and microglia, (3) decreased electroretinogram a- and b-wave amplitudes, (4) reduced visual acuity, and (5) increased polymorphonuclear cell accumulation in vascular lumina abutting venular walls in the retina and in vital non-ocular tissues (lung and liver). Furthermore, PheWAS of CXCR2 CXCR1, and ACKR1 gene variants using data from UK Biobank participants suggest clinical associations with both retinal and vascular disease phenotypes. We conclude that chronic CXCR2 deficiency in mice contributes to functional damage to the retina and that the long-term safety of CXCR1/2 inhibitors designed for chronic use in humans should be explored before clinical adoption to safeguard sight and overall vascular health., (© 2024. The Author(s).)

T cell-mediated islet destruction is a hallmark of autoimmune diabetes. Here, we examined the dynamics and pathogenicity of CD4 + T cell responses to four different insulin-derived epitopes during diabetes initiation in non-obese diabetic (NOD) mice. Single-cell RNA sequencing of tetramer-sorted CD4 + T cells from the pancreas revealed that islet-antigen-specific T cells adopted a wide variety of fates and required XCR1 + dendritic cells for their activation. Hybrid-insulin C-chromogranin A (InsC-ChgA)-specific CD4 + T cells skewed toward a distinct T helper type 1 (Th1) effector phenotype, whereas the majority of insulin B chain and hybrid-insulin C-islet amyloid polypeptide-specific CD4 + T cells exhibited a regulatory phenotype and early or weak Th1 phenotype, respectively. InsC-ChgA-specific CD4 + T cells were uniquely pathogenic upon transfer, and an anti-InsC-ChgA:IAg7 antibody prevented spontaneous diabetes. Our findings highlight the heterogeneity of T cell responses to insulin-derived epitopes in diabetes and argue for the feasibility of antigen-specific therapies that blunts the response of pathogenic CD4 + T cells causing autoimmunity., Competing Interests: Declaration of interests The authors J.A.S. and B.T.F. have a patent related to this work. U.S. Patent No. 15/952,965, title: monoclonal antibodies directed to peptide in the context of MHC and methods of making and using monoclonal antibodies. Office: United States of America., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Ocular levels of IL-1β, TNFα, IL-8, and IL-6 correlate with progression of diabetic retinopathy (DR). Müller cells (MC), which are crucial to maintaining retinal homeostasis, are targets and sources of these cytokines. We explored the relative capacities of these four DR-associated cytokines to amplify inflammatory signal expression both in and between human MC (hMC) and retinal microvascular endothelial cells (hRMEC) and in the mouse retina. Of the four cytokines, IL-1β was the most potent stimulus of transcriptomic alterations in hMC and hRMEC in vitro, as well as in the mouse retina after intravitreal injection in vivo. Stimulation with IL-1β significantly induced expression of all four transcripts in hMC and hRMEC. TNFα significantly induced expression of some, but not all, of the four transcripts in each cell, while neither IL-8 nor IL-6 showed significant induction in either cell. Similarly, conditioned media (CM) derived from hMC or hRMEC treated with IL-1β, but not TNFα, upregulated inflammatory cytokine transcripts in the reciprocal cell type. hRMEC responses to hMC-derived CM were dependent on IL-1R activation. In addition, we observed a correlation between cytokine expression changes following direct and CM stimulation and NFκB-p65 nuclear translocation in both hMC and hRMEC. Finally, in mice, intravitreal injections of IL-1β, but not TNFα, induced retinal expression of Il1b and CXCL8 homologues Cxcl1, Cxcl2, Cxcl3, and Cxcl5, encoding pro-angiogenic chemokines. Our results suggest that expression of IL-1β, TNFα, IL-8, and IL-6 may be initiated, propagated, and sustained by autocrine and paracrine signals in hRMEC and hMC through a process involving IL-1β and NFκB. Targeting these signals may help thwart inflammatory amplification, preventing progression to vision-threatening stages and preserving sight., Competing Interests: Declaration of competing interest There are no financial or non-financial competing interests declared by any author., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Experimenter bias compromises the integrity and advancement of science, especially when awarded as such. For example, the 2022 Nobel Prize in Physics awarded for the loophole-free experiments that tested physicist John S. Bell's inequality theorem. These experiments employed the logic of conducting local experiments to obtain local evidence that contradicted local realistic theories of nature, thereby validating quantum mechanics as a fundamental non-local theory. However, there was one loophole that was wittingly not tested by the Nobel laureates. The notable exception was Bell's "super-deterministic" loophole, which was validated (2000) (2001) (2002) (2003) (2004) (2005) (2006) (2007) (2008) (2009) (2010) (2011) (2012) non-locally, thus compromising the subsequent Nobel Prize. More importantly, the discovery of two mutually exclusive and jointly exhaustive non-local hidden variables revealed why local scientific methods obtain false-positive and false-negative results. With knowledge of this fundamental omission, the inclusion of the non-local hidden variables in the local methods used in science can then advance it to be a complete study of nature., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Morales.)

Background: Vitamin D plays a critical role in immunomodulation, and its deficiency is implicated in the pathogenesis of several autoimmune diseases. Nevertheless, its relationship with non-infectious uveitis (NIU), an inflammatory ocular disorder, remains inconclusive., Methods: A systematic search was conducted in three databases from database inception until May 8, 2023, to investigate the potential relationship between vitamin D deficiency and NIU. We included observational studies reporting the measurement of vitamin D levels in patients with NIU and healthy controls without restriction of language or date of publication. Three pairs of authors independently screened the title and abstracts for potential eligibility and then in full text. A third author resolved disagreements. Three pairs of independent reviewers abstracted the data from the fully reviewed records and evaluated the risk of bias. We followed The MOOSE and PRISMA guidelines. Random effects meta-analyses were used for primary analysis. Studies not included in the meta-analysis were summarized descriptively. This review was registered in PROSPERO: CRD42022308105., Findings: Of 933 records screened, 11 studies were included, and five were meta-analyzed, encompassing 354 cases and 5728 controls (mean participant age ranging from 7.1 to 58.9 years). Patients with vitamin D deficiency exhibited an Odds Ratio of 2.04 (95% CI = 1.55-2.68, P < 0.00001) for developing NIU compared to controls. Overall, potential sources of bias were low across most studies., Interpretation: Our findings suggest that vitamin D may play an essential role in the pathophysiology of NIU. While the included studies demonstrated generally low potential bias, additional rigorous prospective studies are necessary to confirm these findings and further elucidate the underlying mechanisms involved. Vitamin D supplementation could represent a possible therapeutic strategy for preventing or managing NIU if substantiated. Clinicians should consider screening for and addressing vitamin D deficiency in patients with or at risk for NIU., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier B.V.)

We report an isolated outbreak of Rickettsia rickettsii in the Ngäbe-Buglé indigenous region, located 750 m (tropical wet) above sea level, in a jungle and mountainous area of Western Panama. Seven members of a family were infected simultaneously, resulting in four deaths. Family outbreaks have been previously described and are responsible for 4-8% of the cases described [1-4]. The simultaneous onset of symptoms in the affected population group is extremely unusual [1,5], but it should not dissuade the clinician from considering the possibility of Rickettsia rickettsii infection., (Copyright © 2023. Published by Elsevier Ltd.)

Edible insects have become a promising food source because they are rich in protein, fatty acids, minerals, among others. In recent years, edible insects have been proposed to be used as innovative functional ingredients in terms of biological activity. The present study aimed to determine and compare biological activities of the extracts and hydrolysates obtained from early- and adult-stage edible grasshoppers Sphenarium purpurascens to evaluate their potential as a source of bioactive compounds. Proximal analyses showed that in adult grasshoppers (AGs), the percentage of protein (48.9% ± 1.2), crude fat (13.1% ± 0.09), and chitin (15.6% ± 0.81) was significantly higher than early grasshoppers (EGs) (42.2% ± 0.55, 9.35% ± 0.08, and 10.5% ± 0.15, respectively). Total phenolic compounds, 2,2-diphenyl-1-picrylhydrazyl (DPPH•), and 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS•+) free radical scavenging were analyzed and reported. Enzymatic hydrolysis increased the concentration of total phenolic compounds and higher antioxidant capacity (up to 252.78 mM trolox). Once fractionated by ultrafiltration, the fraction that presented the highest antioxidant activity against DPPH• and ABTS•+ was that with molecules ≤ 10 kDa. Furthermore, the bioaccessibility of the samples was analyzed by in vitro protein digestion using a multienzymatic method, and a recovery index (RI) was reported. Extracts and hydrolysates were analyzed by UPLC-MS, and this allowed the identification of phenolic acids and flavonoids. The results obtained in this work suggest that the grasshopper can be used as a possible source of bioactive compounds that can be used in the food or pharmaceutical industry., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Marín-Morales, Ibarra-Herrera, Luna-Vital, Monribot-Villanueva and Guerrero-Analco.)

The potential for explosive volcanism to affect the El Niño-Southern Oscillation (ENSO) has been debated since the 1980s. Several observational studies, based largely on tree-ring proxies, have since found support for a positive ENSO phase in the year following large eruptions. In contrast, recent coral data from the heart of the tropical Pacific suggest no uniform ENSO response to explosive volcanism over the last millennium. Here we leverage paleoclimate data assimilation to integrate both tree-ring and coral proxies into a reconstruction of ENSO state, and re-appraise this relationship. We find only a weak statistical association between volcanism and ENSO, and identify the selection of volcanic events as a key variable to the conclusion. We discuss the difficulties of conclusively establishing a volcanic influence on ENSO by empirical means, given the myriad factors affecting the response, including the spatiotemporal details of the forcing and ENSO phase preconditioning., (© 2022. The Author(s).)

Tree growth is generally considered to be temperature limited at upper elevation treelines, yet climate factors controlling tree growth at semiarid treelines are poorly understood. We explored the influence of climate on stem growth and stable isotopes for Polylepis tarapacana Philipi, the world's highest elevation tree species, which is found only in the South American Altiplano. We developed tree-ring width index (RWI), oxygen (δ18O) and carbon (δ13C) chronologies for the last 60 years at four P. tarapacana stands located above 4400 m in elevation, along a 500 km latitude aridity gradient. Total annual precipitation decreased from 300 to 200 mm from the northern to the southern sites. We used RWI as a proxy of wood formation (carbon sink) and isotopic tree-ring signatures as proxies of leaf-level gas exchange processes (carbon source). We found distinct climatic conditions regulating carbon sink processes along the gradient. Current growing-season temperature regulated RWI at northern-wetter sites, while prior growing-season precipitation determined RWI at arid southern sites. This suggests that the relative importance of temperature to precipitation in regulating tree growth is driven by site water availability. By contrast, warm and dry growing seasons resulted in enriched tree-ring δ13C and δ18O at all study sites, suggesting that similar climate conditions control carbon-source processes along the gradient. Site-level δ13C and δ18O chronologies were significantly and positively related at all sites, with the strongest relationships among the southern drier stands. This indicates an overall regulation of intercellular carbon dioxide via stomatal conductance for the entire P. tarapacana network, with greater stomatal control when aridity increases. This manuscript also highlights a coupling (decoupling) between physiological processes at leaf level and wood formation as a function of similarities (differences) in their climatic sensitivity. This study contributes to a better understanding and prediction of the response of high-elevation Polylepis woodlands to rapid climate changes and projected drying in the Altiplano., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

The objective of this study was to compare the effect of contrasting sources of dietary n-6 and n-3 PUFA on expression of genes related to lipid metabolism in dairy cows. During 63 days, fifteen lactating cows were assigned to a control or basal diet containing no added lipid (n = 5 cows); and treatment diets supplemented with SO (n = 5 cows; unrefined soybean oil; 2.9% of DM) or FO (n = 5 cows; fish oil manufactured from salmon oil; 2.9% of DM). Plasma for fatty acid (FA) analysis and milk somatic cells (MSC) were obtained from all cows at the beginning of the study (day 0) and on days 21, 42 and 63. Plasma was used to determine FA transport dynamics. Compared with control and FO, plasma from SO had increased contents of C18:1 cis-9, C18:1 trans-11, C18:2 cis-9, trans-11 and total monounsaturated FA. On the other hand, compared with control and SO, FO increased plasma contents of C20:3 n-3, C20:3 n-6, C20:4 n-6, C20:5 n-3, C22:6 n-3 and total polyunsaturated FA. Moreover, plasma C18:3 n-3 and C20:5 n-3 increased over time for all diets. Compared with control, SO downregulated ACACA, INSIG1, and DGAT1, whereas FO downregulated ACACA, PPARGC1, LPIN1 and FABP3 on day 63, in MSC. At different time-points, SO and FO downregulated genes related to synthesis and intracellular transport of FA, synthesis of triglycerides, and transcription factors.

South American (SA) societies are highly vulnerable to droughts and pluvials, but lack of long-term climate observations severely limits our understanding of the global processes driving climatic variability in the region. The number and quality of SA climate-sensitive tree ring chronologies have significantly increased in recent decades, now providing a robust network of 286 records for characterizing hydroclimate variability since 1400 CE. We combine this network with a self-calibrated Palmer Drought Severity Index (scPDSI) dataset to derive the South American Drought Atlas (SADA) over the continent south of 12°S. The gridded annual reconstruction of austral summer scPDSI is the most spatially complete estimate of SA hydroclimate to date, and well matches past historical dry/wet events. Relating the SADA to the Australia-New Zealand Drought Atlas, sea surface temperatures and atmospheric pressure fields, we determine that the El Niño-Southern Oscillation (ENSO) and the Southern Annular Mode (SAM) are strongly associated with spatially extended droughts and pluvials over the SADA domain during the past several centuries. SADA also exhibits more extended severe droughts and extreme pluvials since the mid-20th century. Extensive droughts are consistent with the observed 20th-century trend toward positive SAM anomalies concomitant with the weakening of midlatitude Westerlies, while low-level moisture transport intensified by global warming has favored extreme rainfall across the subtropics. The SADA thus provides a long-term context for observed hydroclimatic changes and for 21st-century Intergovernmental Panel on Climate Change (IPCC) projections that suggest SA will experience more frequent/severe droughts and rainfall events as a consequence of increasing greenhouse gas emissions., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

Objective: To develop and validate syringe threat and injury correlates (STIC) score to measure police vulnerability to needlestick injury (NSI)., Methods: Tijuana police officers (N = 1788) received NSI training (2015 to 2016). STIC score incorporates five self-reported behaviors: syringe confiscation, transportation, breaking, discarding, and arrest for syringe possession. Multivariable logistic regression was used to evaluate the association between STIC score and recent NSI., Results: Twenty-three (1.5%) officers reported NSI; higher among women than men (3.8% vs 1.2%; P = 0.007). STIC variables had high internal consistency, a distribution of 4.0, a mode of 1.0, a mean (sd) of 2.0 (0.8), and a median (interquartile range [IQR]) of 2.0 (1.2 to 2.6). STIC was associated with recent NSI; odds of NSI being 2.4 times higher for each point increase (P-value <0.0001)., Conclusions: STIC score is a novel tool for assessing NSI risk and prevention program success among police.

This study analyzed effects of vegetable oils fed to dairy cows on abundance of genes related to lipid metabolism in milk somatic cells (MSC). During 63 days, 15 cows were allocated to 3 treatments: a control diet with no added lipid the same diet supplemented with olive oil (OO, 30 g/kg DM) or hydrogenated vegetable oil (HVO, 30 g/kg DM). On days 21, 42 and 63, MSC were obtained from all cows. Relative abundance of genes involved in lipid metabolism in MSC from cows fed control on days 42 and 63 was compared with relative abundance at day 21 to evaluate fold-changes. Those genes without changes over the time were selected to analyze effects of OO and HVO. Compared with control, on day 42, PLIN2 and THRSP were upregulated by OO. Compared with control, on day 21, HVO up regulated ACACA , down regulated FABP3 , and on day 63 THRSP and FABP4 were down regulated. Dietary oil supplementation (3% DM) had a modest nutrigenomic effect on different biological functions such as acetate and FA activation and intra-cellular transport, lipid droplet formation, and transcription regulation in MSC.

The objective of this study was to determine the effect of long-term supplementation of unsaturated oil on lipid metabolism and transcription of genes involved in lipid metabolism in subcutaneous adipose tissue (SAT) of mid-lactating dairy cows. The objective was achieved by supplementing dairy cows with soybean oil (SO; high in linoleic acid) or fish oil (FO; high in EPA and DHA) for 63 days (nine weeks). Cows were fed a control diet with no added lipid, or diets containing SO or FO (n = 5 cows/group). At the onset of the experiment (day 0) and on days 21, 42, and 63 of supplementation, blood and SAT samples were collected from each animal. Oil supplementation increased cholesterol and NEFA in plasma, with a greater effect of SO compared to FO. Concentration of BUN was lower in SO compared to control and FO at the end of the trial. Transcription of few genes was affected by dietary lipids: FABP4 had lowest expression in FO followed by SO and control. ACACA and FASN had higher expression in FO. Transcription of SCAP was higher but expression of INSIG1 was lower in SO. Overall, results revealed that compared to control, SO and FO had lipogenic effect in SAT.

The objective of this study was to characterize the long-term transcriptomic effects of lipogenic genes in subcutaneous adipose tissue (SAT) of dairy cows supplemented with unsaturated (olive oil; OO) and saturated (hydrogenated vegetable oil; HVO) lipids. Cows were fed a control diet with no added lipid, or diets containing OO or HVO (n = 5 cows/group) for 63 days. SAT was obtained from the tail-head area at the onset of the study and after 21, 42, and 63 days of supplementation. Treatments had minor effects on expression of measured genes. Both fat supplements reduced expression of PPARG , HVO decreased transcription of the desaturase FADS2 and lipid droplet formation PLIN2 , and OO increased transcription of FABP3 . Both lipid treatments decreased expression of the transcription regulator SREBF1 and its chaperone ( SCAP ) during the first 21 days of treatment. Our data indicated that long-term feeding of OO and HVO have a relatively mild effect on expression of lipogenic genes in SAT of mid-lactating cows.

The objective of this study was to evaluate the effects of supplementation of dairy cows with different fatty acid sources (soybean oil (SO) and fish oil (FO)) on milk production, milk composition, milk fatty acid profile, and physicochemical and sensory characteristics of ice cream. During 63 days, fifteen Holstein cows averaging 198 ± 35 days in milk were assigned to three groups: control diet with no added lipid ( n = 5 cows); and supplemented diets with SO ( n = 5 cows; unrefined SO; 30 g/kg DM) or FO ( n = 5 cows; FO from unrefined salmon oil; 30 g/kg DM). Milk production, milk fat, and milk protein were not affected by treatments. Saturated fatty acids in milk fat were decreased with SO and FO compared with control. C18:2 cis -9, cis -12 was increased with SO whereas C18:2 cis -9, trans -11, C20:3n-3, C20:3n-6, C20:5n-3, and C22:6n-3 were the highest with FO. Draw temperature and firmness were higher in SO compared to control and FO ice creams. Melting resistance was higher in FO compared with control and SO ice creams. Supplementation of cow diets with SO and FO did not have detrimental effects on milk production, or ice cream physicochemical and sensory characteristics.

Background: Despite the proven efficacy of vedolizumab (VDZ) for ulcerative colitis (UC) and Crohn's disease (CD), suboptimal response is commonly encountered. However, data regarding the effectiveness of dose intensification (by interval shortening) to achieve response are limited., Objectives: We evaluated the effectiveness of dose intensification at achieving response in patients with a previously suboptimal response to VDZ. Additionally, we aimed to identify predictors of response to this strategy., Methods: We performed a retrospective cohort study of patients who underwent VDZ dose intensification for suboptimal response. Clinical disease activity was evaluated at the point of dose intensification (baseline) and at weeks 12 and 24. Response was defined as Harvey-Bradshaw Index (HBI) or Simple Clinical Colitis Activity Index (SCCAI) reduction of ≥3, and remission as HBI <5 or SCCAI <3., Results: A total of 36 patients received dose intensification to 4-weekly infusions: 18 CD, 14 UC and 4 inflammatory bowel disease-unclassified (analysed in the UC group). Median SCCAI scores fell from 6 (range 0-11) at baseline to 4 (0-6, p=0.008) at week 24, while HBI scores did not change significantly (4 (0-27) and 3 (0-8), p=0.092). Overall median C reactive protein (CRP) fell from 6 mg/L (1-23) to 2 mg/L (1-17, p=0.011). Of 20 patients with clinically active disease at baseline, 10 (50%) responded, of whom 4 (20%) achieved remission at week 24. Univariate analysis demonstrated low baseline CRP (p=0.045) and response at week 12 (0.020) were associated with week 24 response., Conclusions: Our findings demonstrate VDZ dose intensification to be effective at achieving clinical response in half of patients. Low baseline CRP and response at week 12 are potential predictors of week 24 response., Competing Interests: Competing interests: MAS: served as a speaker, a consultant and/or an advisory board member for Janssen, Takeda, MSD and Falk. MSM: served as a speaker for Takeda. SH: served as a speaker for Janssen. PMI: served as a speaker, a consultant and/or an advisory board member for AbbVie, Warner Chilcott, Ferring, Falk Pharma, Takeda, MSD, Johnson & Johnson, Shire, Vifor Pharma, Pharmacosmos, Topivert, Genentech, Hospira and Samsung Bioepis, and has received research funding from MSD and Takeda., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Older hypertensive adults under treatment are especially susceptible to hypotensive episodes, which entail an elevated risk. However, data on this subject are very scarce., Aim: The purpose of this study was to determine the prevalence and predictors of office and home hypotension in older (≥ 65 years) treated hypertensive adults., Methods: Blood pressure (BP) was measured at the office and at home, using a validated oscillometric device. Office and home hypotension were defined as systolic BP (SBP) < 110 and/or diastolic BP (DBP) < 70 mmHg, and SBP < 105 and/or DBP < 65 mmHg, respectively. Masked hypotension was considered when office BP ≥ 110/70 and home BP < 105 and/or < 65 mmHg. We evaluated factors associated with hypotension both at the office and at home through multivariable models., Results: The prevalence of hypotension among the 302 patients included in the study was 29.8% at the office and 23.9% at home, whereas the prevalence of masked hypotension was 10.4%. Older age, lower body mass index and use of calcium channel blockers were associated with office hypotension, while older age, diabetes and ischemic heart disease were predictors for home hypotension., Conclusion: Hypotension is frequent in older hypertensive adults under treatment. The presence of diabetes, ischemic heart disease and older age should alert for screening of hypotension at home to avoid overtreatment.

The blood pressure measurement method that more accurately predicts a left ventricular mass is controversial, and the evidence suggesting superiority of central over brachial measurements is contradictory. The aim of this study was to compare the relationship between the different clinic and out-of-clinic blood pressure measurements methods with left ventricular mass in patients who attended a specialised hypertension centre for a central blood pressure measurement. An analysis was performed on the correlations between left ventricular mass and central and brachial blood pressure measurements made in the clinic, and home, as well as 24-h systolic blood pressure measurements. A linear regression analysis was then performed to assess the independent relationship of each blood pressure measurement with left ventricular mass. The results on 824 treated and 123 untreated patients showed no significant differences between correlations, although home readings tended to have the best correlations. In regression adjusted models, for each 10 mmHg increase in systolic home blood pressure the left ventricular mass increased 10 g/m 2 (95% CI; 3.7-27, p=.01, adj R 2 0.38), and for 24-h ambulatory systolic blood pressure it increased 2.3 g/m 2 (95% CI 0.76-3.9, p<.01, adj R 2 0.15) in treated and untreated patients, respectively. The association of systolic blood pressure with left ventricular mass was better explained by home and 24-h ambulatory monitoring than to clinic-based measurements in treated and untreated patients, respectively. In the clinic, however, the central measurement was not superior to brachial blood pressure., (Copyright © 2018 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.)

Aims and Objectives: To evaluate both concordance among those measurements obtained by three different pulse oximeters currently used by nursing professionals in hospital units and the factors which can influence this concordance., Background: Many models of wireless pulse oximeters in the present market do not offer possibility of calibration and, therefore, they do not ensure patients' safety in daily clinical practice., Design: This is a descriptive and cross-sectional study. The sample of patients (140) was selected from such hospital units, and all of them had to fulfil inclusion and exclusion criteria for participation., Methods: The instruments used to carry out this research were a monitor (calibrated), two models of portable wireless pulse oximeters (used for 3 years by the nursing staff, without being calibrated), a tympanic thermometer and a weather meter. The concordance correlation coefficient (CCC) was used to establish the concordance, whereas the Landis-Koch criteria were used to interpret the results., Results: The concordance among the three devices was considered as "good" (CCC: 0.925 and 0.974 (95%)). The CCC (0.925) for saturation measures was regarded as "very good"/"almost perfect," and the pulse measure was considered as "very good" CCC 0.974, providing in both cases a high level of concordance (CCC > 0.91)., Conclusions: The overall concordance as regards pulse and oxygen saturation among the three pulse oximeters analysed is considered as "very good" according to the Landis-Koch criteria., Relevance to Clinical Practice: There exists a "very good" concordance among two wireless oximeters which have been used by the health staff for 3 years and which did not offer any possibility of calibration and one monitor which belongs to the healthcare institution. This aspect is of crucial importance in daily clinical practice, and it is also relevant to ensure patient's safety., (© 2017 John Wiley & Sons Ltd.)

Objective: The objective of this study was to compare the aortic piezoelectric device for noninvasive measurement of central aortic systolic blood pressure (cSBP) with the SphygmoCor., Participants and Methods: A total of 85 participants from both sexes, aged 18-80 years, were stratified into three age groups (<30, 30-60, >60 years), with an equal number of healthy volunteers and hypertensive patients. We performed three cSBP measurements with each device, in an alternate manner, using the Bland-Altman method to determine the level of agreement. The standard of the Association for the Advancement of Medical Instrumentation for brachial blood pressure evaluation was used for the comparison., Results: The mean cSBPs were 109.3±12.05 and 109.0±12.2 mmHg with the SphygmoCor and the Aortic device, respectively, showing a strong correlation (r=0.98, P<0.001). A mean difference of 0.35±2.43 mmHg (95% confidence interval: 0.17-0.87, P=NS) was obtained with the Bland-Altman method. The 95% limits of agreement was -4.4 to +5.1 mmHg., Conclusion: Complying with the Association for the Advancement of Medical Instrumentation criteria, cSBP measurements obtained with the Aortic and the SphygmoCor devices are equivalent.

Exaggerated orthostatic blood pressure variation (EOV) is a poorly understood phenomenon related to high cardiovascular risk. We aimed to determine whether hypertensive patients with EOV have a distinct hemodynamic pattern, assessed through impedance cardiography., Methods: In treated hypertensive patients, we measured the cardiac index (CI), systemic vascular resistance index (SVRI), blood pressure (BP), and heart rate (HR) in the supine and standing (after 3 minutes) positions, defining three groups according to BP variation: 1) Normal orthostatic BP variation (NOV): standing systolic BP (stSBP)-supine systolic BP (suSBP) between -20 and 20 mmHg and standing diastolic BP (stDBP)-supine diastolic BP (suDBP) between -10 and 10 mmHg; 2) orthostatic hypotension (OHypo): stSBP-suSBP≤-20 or stDBP-suDBP≤-10 mmHg; 3) orthostatic hypertension (OHyper): stSBP-suSBP≥20 or stDBP-suDBP≥10 mmHg. We performed multivariable analyses to determine the association of hemodynamic variables with EOV., Results: We included 186 patients. Those with OHyper had lower suDBP and higher orthostatic SVRI variation compared to NOV. In multivariable analyses, orthostatic HR variation (OR = 1.06 (95%CI 1.01-1.13), p = 0.03) and orthostatic SVRI variation (OR = 1.16 (95%CI 1.06-1.28), p = 0.002) were independently related to OHyper. No variables were independently associated with OHypo., Conclusion: Patients with OHyper have a distinct hemodynamic pattern, with an exaggerated increase in SVRI and HR when standing.

Background: High-protein diets have been shown to improve body composition through alterations in satiety, muscle protein synthesis, and the thermic effect of food., Aim: Given these findings, the purpose of this review is to discuss the integration of the specific hormonal and metabolic effects of high-protein diets following both acute and long-term usage, especially with regard to body composition., Methods: Full-text articles were obtained through PubMed by using the terms "high-protein diet and body composition," "high-protein diet and exercise," "high-protein diet risk," "high-protein diet side effects," "protein quality PDCAAS," "RDA for protein," and "daily protein recommendation." Articles were initially screened according to their title and abstract; careful evaluation of the full manuscripts was then used to identify relevant articles., Results: The higher satiety exerted by high-protein diets is generated through increments in anorexigenic, as well as decrements in orexigenic hormones. Improvements in muscle mass are achieved by activation of muscle protein synthesis acting through the mTOR pathway. High thermic effect of food is caused due to necessary deamination, gluconeogenesis, and urea synthesis caused by high-protein diets. Interestingly, high-protein diets in both hypo- and normocaloric conditions have shown to improve body composition, whereas in combination with hypercaloric conditions does not seem to increase fat mass, when the excess energy comes from protein., Conclusions: High protein diets effectively improve body composition by acting through different pathways.

Arterial stiffness, assessed through pulse wave velocity (PWV), independently predicts cardiovascular outcomes. In untreated persons, white-coat hypertension (WCH) has been related to arterial stiffness, but data in treated patients with WCH are scarce. The authors aimed to determine a possible association between WCH and arterial stiffness in this population. Adult treated hypertensive patients underwent home blood pressure monitoring and PWV assessment. Variables associated with PWV in univariable analyses were entered into a multivariable linear regression model. The study included 121 patients, 33.9% men, median age 67.9 (interquartile range 18.4) years, 5.8% with diabetes, and 3.3% with a history of cardiovascular or cerebrovascular disease. In multivariable analysis, WCH in treated hypertensive patients remained a determinant of PWV: β=1.1 (95% confidence interval, 0.1-2.1 [P=.037]; adjusted R 2 0.49). In conclusion, WCH is independently associated with arterial stiffness in treated hypertensive patients. Whether this high-risk association is offset by antihypertensive treatment should be further investigated., (©2016 Wiley Periodicals, Inc.)

Background: An alerting reaction is a physician-induced phenomenon which produces a transient blood pressure rise in the office., Objective: To determine its relationship with target organ damage in treated hypertensives., Method: We used three different indexes for calculating alerting reaction depending on the first, second or third office blood pressure measurement. We correlated these indexes with glomerular filtration rate, left ventricular mass index and pulse wave velocity. Thereafter, for multivariate analysis, we selected the index which better correlated with each target organ damage subtype., Results: We included 174 adults, mean age 67(±13.7) years. 75% of the patients had some degree of blood pressure fall between measurements 1-3. In multivariate linear regression models, after adjusting for classic risk factors, two out of the three systolic alerting reaction indexes showed an independent association with target organ damage. After further adjusting for office blood pressure and white coat effect (calculated with standardized home blood pressure monitoring), left ventricular mass index maintained a statistically significant association., Conclusion: A higher alerting reaction in the office seems to be related to increased target organ damage in treated hypertensives and should not be considered an innocent phenomenon., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Heme iron (Fe) release from alginate beads at in vitro simulated gastrointestinal conditions for potential use as oral heme Fe supplement was studied. Five beads at different ratios of sodium alginate (SA)-to-spray-dried bovine blood cells (SDBC) with weight ratios of 1:1.25, 1:2.5, 1:5, 1:10, and 1:15 (w/w) were prepared. Release characteristics of these beads were investigated at in vitro simulated gastrointestinal conditions. Release media pH strongly influenced the controlled Fe release from the beads. The heme Fe-beads in simulated gastric fluid (pH 2) remained in a shrinkage state and Fe release was low: 25.8, 21.1, 11.6, 12.1, and 12.0 % for 1:1.25, 1:2.5, 1:5, 1:10, and 1:15 ratios, respectively. Proportion and amount of Fe released by 1:1.25 and 1:2.5 ratios was higher than the other ratios. The heme Fe-beads swelled and dissociated in simulated intestinal fluid (pH 6), releasing three-fourths of the Fe in 200 min. The morphology studies showed that Fe release followed formation of pores in the alginate matrix, generating erosion of the beads and complete disintegration after 75 and 200 min of gastric and intestinal incubation, respectively. These results indicate that heme Fe-beads may be useful for oral delivery of heme Fe supplement.

Purpose: The aim of this study was to investigate possible functional and structural ocular changes caused by chronic sildenafil therapy to treat pulmonary arterial hypertension (PAH)., Methods: Case-control study included patients with pulmonary arterial hypertension: chronically using sildenafil and without sildenafil treatment. A comprehensive ophthalmologic exam including ectoscopy, extrinsic ocular motility, logMAR visual acuity measurement, contrast sensitivity test, color test, anterior segment biomicroscopy, Schirmer test 1, intraocular pressure, fundus exam under pupil dilation, fundus pictures, time domain and spectral domain optical coherence tomography, ocular Doppler ultrasound were performed. Full-field electroretinography (ERG) was tested for each eye in a subgroup of sildenafil-treated patients., Results: Twenty patients from each group were tested. Bilateral severe keratitis was found in seven (35 %) patients under sildenafil therapy. Lacrimal film break-up time (BUT) was significantly reduced (p = 0.006 respectively) and Doppler ultrasound showed a reduced resistance index of the central retinal artery in the group of sildenafil users (p = 0.019). No diffuse retinal functional abnormalities were found in ERG in treated patients. Visual acuity, contrast sensitivity and color discrimination were normal in both groups. No abnormalities were found in both time-domain and spectral-domain OCT for retinal parameters., Conclusions: One-third of the treated PAH group showed severe bilateral keratitis. This finding could be related to connective tissue abnormalities usually present in patients with this condition that might be exacerbated with the sildenafil usage. The resistance index of the central retinal artery was diminished in the chronic users group and it could be associated to the vasodilation caused by the medication in the choroidal vessels. An ophthalmic assessment for these patients is recommended to diagnose and treat possible ocular surface and choroidal blood flow abnormalities caused by sildenafil.

Background and Objective: To study the correlation between the choroidal thickness (CT) measured by spectral-domain optical coherence tomography (SD-OCT) and retrobulbar blood flow measured by color Doppler flowmetry (CD) in normal subjects., Patients and Methods: Healthy subjects underwent enhanced-depth imaging SD-OCT and CD using a linear 6 MHz to 18 MHz transducer. The maximal peak systolic velocity and resistance index (RI) were obtained for the ophthalmic artery (OA), short posterior ciliary artery (SPCA), and central retinal artery (CRA) and correlated with the subfoveal CT measured by SD-OCT., Results: Twenty-seven eyes of 27 healthy patients were enrolled (mean age: 40.6 ± 12.4 years; range: 27-68 years). An inverse proportional relationship (P = .0496) was identified between the RI of the SPCA (mean, 0.6117 ± 0.07911) and the subfoveal CT (319.9 µm ± 83.79 µm) but not between the RI and the OA (mean: 0.7019 µm ± 0.07317 µm) or the CRA (mean: 0.68843 µm ± 0.08994 µm)., Conclusion: The results of this study suggested there is an inverse proportional relationship between the RI of the SPCA and the subfoveal CT. The data also suggested a correlation between a decrease in the CT and increased RI in the retrobulbar arteries. Therefore, lower choroidal blood flow may explain the thinner CT in normal subjects., (Copyright 2015, SLACK Incorporated.)

The purpose is to document a case of persistent hiperplastic primary vitreous (PHPV) with atypical Bergmeister's papilla and patent hialoid artery that had its conclusive diagnosis done by doppler ultrasound. We report a case of child, who had unilateral leucokoria. This child's fundoscopic examination showed a white mass on the optic nerve that extended over to adjacent retina. Performed ultrasound that remained a doubt with the following diagnostic hypotheses: persistent hiperplastic primary vitreous, granuloma (toxocara), astrocytic hamartoma and retinoblastoma. The diagnosis was only established when the doppler ultrasound showed a blood flow inside of the membrane, thus confirming the diagnosis of persistent hiperplastic primary vitreous associated with the Bergmeister'spapilla.

We aimed to compare atenolol versus bisoprolol regarding general hemodynamics, central-peripheral blood pressure (BP), pulse wave parameters, and arterial stiffness. In this open-label, crossover study, we recruited 19 hypertensives, untreated or with stable monotherapy. Patients were randomized to receive atenolol (25-50 mg) or bisoprolol (2.5-5 mg), and then switched medications after 4 weeks. Studies were performed at baseline and after each drug period. In pulse wave analyses, both drugs significantly increased augmentation index (P < .01) and ejection duration (P < .02), and reduced heart rate (P < .001), brachial systolic BP (P ≤ .01), brachial diastolic BP (P ≤ .001), and central diastolic BP (P ≤ .001), but not central systolic BP (P ≥ .06). Impedance cardiographic assessment showed a significantly increased stroke volume (P ≤ .02). There were no significant differences in the effects between drugs. In conclusion, atenolol and bisoprolol show similar hemodynamic characteristics. Failure to decrease central systolic BP results from bradycardia with increased stroke volume and an earlier reflected aortic wave., (Copyright © 2015 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

We aimed to determine the characteristics of home blood pressure (BP) in very elderly hypertensives. A total of 485 treated hypertensive patients ≥18 years (median age, 70.8 [interquartile range, 18]; 67.2% women) underwent home BP measurements. Characteristics of patients ≥80 and <80 years of age and prevalence of office and home uncontrolled hypertension, isolated morning (IMH), isolated evening, isolated office, and masked hypertension were compared. Very elderly subjects had higher levels of systolic and lower levels of diastolic BP at home, a higher prevalence of home uncontrolled hypertension (68.5% vs. 37.7%; P < .001), masked hypertension (30.6% vs. 14.9%; P = .02), and IMH (19.4% vs. 10.9%; P = .02), and a lower prevalence of isolated office hypertension (8.3% vs. 18.8%; P = .01). When using differential home BP thresholds in the very elderly, determined through the percentile method, statistical differences disappeared, except for IMH. The very elderly depict a particular home BP profile. Benefit from using differential home BP thresholds should be determined in prospective studies., (Copyright © 2015 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

We aimed to determine a possible association between isolated morning hypertension (IMH) and meal-induced blood pressure (BP) fall in adult treated hypertensive patients who underwent home BP measurements. A total of 230 patients were included, median age 73.6, 65.2% women. After adjusting for age, sex, number of antihypertensive drugs, office and home BP levels, the association between IMH and meal-induced BP fall was statistically significant. In conclusion, meal-induced BP fall and IMH detected through home blood pressure monitoring (HBPM) are independently associated in hypertensive patients. The therapeutic implications of such observation need to be clarified in large-scale prospective studies.

Purpose: To describe quantitative and qualitative features of eyes with advanced bullous keratopathy assessed using ultrasound biomicroscopy, before and after anterior stromal puncture (ASP) or amniotic membrane transplantation (AMT) procedures to relieve chronic pain., Methods: The present descriptive comparative study included 40 eyes of 40 patients with chronic intermittent pain due to bullous keratopathy who were randomly assigned to one of the two treatments (AMT or ASP). Ultrasound biomicroscopy (Humphrey, UBM 840, 50 MHz transducer, immersion technique) was used, and a questionnaire about pain intensity was completed preoperatively and postoperatively at days 90 and 180, respectively. Exclusion criteria were age<18 years, presence of concurrent infection, ocular hypertension, and absence of pain., Results: In a 180-day follow-up, the AMT group exhibited mean central corneal thickness (CCT), 899.4 µm preoperatively and 1122.5 µm postoperatively (p<0.001); mean epithelial thickness (ET), 156.4 µm preoperatively and 247.8 µm postoperatively (p<0.001); and mean stromal thickness (ST), 742.9 µm preoperatively and 826.3 µm postoperatively (p=0.005). The ASP group exhibited mean CCT, 756.7 µm preoperatively and 914.8 µm postoperatively (p<0.001); mean ET, 102.1 µm preoperatively and 245.2 µm postoperatively (p<0.001); and mean ST, 654.6 µm preoperatively and 681.5 µm postoperatively (p<0.999). Correlations between CCT and pain intensity in the AMT group (p=0.209 pre- and postoperatively) and the ASP group (p=0.157 preoperatively and p=0.426 at the 180-day follow-up) were not statistically significant. Epithelial and stromal edema, Descemet's membrane folds, epithelial bullae, and the presence of interface fluid were frequently observed qualitative features., Conclusion: CCT increased over time in both groups. The magnitude of CCT did not correlate with pain intensity in the sample studied. The presence of interface fluid was a qualitative feature specifically found in some patients who underwent AMT.

Information available on the role of Mg for growth and cellulose degradation by rumen bacteria is both limited and inconsistent. In this study, the Mg requirements for two strains each of the cellulolytic rumen species Fibrobacter succinogenes (A3c and S85), Ruminococcus albus (7 and 8) and Ruminococcus flavefaciens (B34b and C94) were investigated. Maximum growth, rate of growth and lag time were all measured using a complete factorial design, 2(3)×6; factors were: strains (2), within species (3) and Mg concentrations (6). R. flavefaciens was the only species that did not grow when Mg was singly deleted from the media, and both strains exhibited a linear growth response to increasing Mg concentrations (P<0.001). The requirement for R. flavefaciens B34b was estimated as 0.54 mM; whereas the requirement for R. flavefaciens C94 was >0.82 as there was no plateau in growth. Although not an absolute requirement for growth, strains of the two other species of cellulolytic bacteria all responded to increasing Mg concentrations. For F. succinogenes S85, R. albus 7 and R. albus 8, their requirement estimated from maximum growth was 0.56, 0.52 and 0.51, respectively. A requirement for F. succinogenes A3c could not be calculated because there was no solution for contrasts. Whether R. flavefaciens had a Mg requirement for cellulose degradation was determined in NH3-free cellulose media, using a 2×4 factorial design, 2 strains and 4 treatments. Both strains of R. flavefaciens were found to have an absolute Mg requirement for cellulose degradation. Based on reported concentrations of Mg in the rumen, 1.0 to 10.1 mM, it seems unlikely that an in vivo deficiency of this element would occur.

Postprandial hypotension (PPH) is a frequently under-recognized entity associated with increased morbidity and mortality. The prevalence of PPH detected through home blood pressure monitoring (HBPM) is unknown. To determine the prevalence and clinical predictors of PPH in hypertensive patients assessed through HBPM. Hypertensive patients of 18 years or older underwent home blood pressure (BP) measurements (duplicate measurements for 4 days: in the morning, 1 h before and 1 h after their usual lunch, and in the evening; OMRON 705 CP). PPH was defined as a meal-induced systolic BP decrease of ≥20 mm Hg. Variables identified as relevant predictors of PPH were entered into a multivariate logistic regression analysis. In total, 230 patients were included in the analysis, with a median age of 73.6 (interquartile range 16.9) years, and 65.2% were female. The prevalence of PPH (at least one episode) was 27.4%. Four variables were independently associated with PPH: age of 80 years or older (odds ratio (OR) 3.45, 95% confidence interval (CI) 1.35-8.82), body mass index (BMI) (OR 0.88, 95%CI 0.81-0.96), office systolic BP (OR 1.03, 95%CI 1.01-1.05) and a history of cerebrovascular disease (OR 3.29, 95%CI 1.03-10.53). PPH after a typical meal is a frequent phenomenon that can be detected through HBPM. Easily measurable parameters in the office such as older age, higher systolic BP, lower BMI and a history of cerebrovascular disease may help to detect patients at risk of PPH who would benefit from HBPM.

Unlabelled: The morning blood pressure (BP) rise entails a higher cardiovascular risk. Studies evaluating the association between home BP morning rise and target organ damage are scarce and almost exclusively based on Asians. The aim of our study was to characterize hypertensive patients with morning rise in home BP and to establish a possible association with left ventricular hypertrophy (LVH)., Methods: treated hypertensive patients ≥ 18 years underwent home BP measurements (duplicate measurements for 4 days in the morning, afternoon and evening), and completed a questionnaire regarding risk factors and history of cardiovascular disease. Medical records were reviewed to extract data from grams. A morning rise in systolic home BP was defined as a difference between morning and evening systolic BP averages ≥15 mmHg. Subjects were considered to have LVH if the left ventricular mass index was >95 g/m2 in women and >115 g/m2 in men. Variables identified as relevant predictors of home BP morning rise were entered into a multivariable logistic regression analysis model., Results: 216 patients were included, mean age 68 (+13.3), 69.4% women and 99.1% Caucasians. The prevalence of BP morning rise was 13.4% and independently associated factors were LVH (OR 3.5; 95%CI 1.1-11.4), age (OR 1.05; 95%CI 1.003-1.1) and a history of cerebrovascular disease (OR 3.9; 95%CI 1.1-14.2). In conclusion, a morning rise in systolic BP detected through home BP monitoring is independently associated with LVH, age and a history of cerebrovascular disease. The therapeutic implications of this observation need to be clarified in large-scale prospective studies.

The prognostic value of impedance cardiography (ICG; cardiac index [CI] and systemic vascular resistance index [SVRI] were measured) was assessed in this retrospective cohort study. A total of 1151 hypertensive outpatients >50 years with a baseline ICG were included. After median follow-up of 3.9 years, for the composite endpoint of cardiovascular events and stroke, adjusted HR for each 500 ml/min/m(2) CI increase was 0.85 (CI95% 0.73-0.9, p = 0.039), and for each 500 dynes s cm(-5) SVRI increase was 1.11 (CI95% 1.01-1.23, p = 0.046), whereas adjusted HR for all-cause mortality was not significant. ICG adds prognostic value to conventional risk factors in hypertensive patients.

Background. The morning home blood pressure (BP) rise is a significant asymptomatic target organ damage predictor in hypertensives. Our aim was to evaluate determinants of home-based morning-evening difference (MEdiff) in Argentine patients. Methods. Treated hypertensive patients aged ≥18 years participated in a cross-sectional study, after performing home morning and evening BP measurement. MEdiff was morning minus evening home average results. Variables identified as relevant predictors were entered into a multivariable linear regression analysis model. Results. Three hundred sixty-seven medicated hypertensives were included. Mean age was 66.2 (14.5), BMI 28.1 (4.5), total cholesterol 4.89 (1.0) mmol/L, 65.9% women, 11.7% smokers, and 10.6% diabetics. Mean MEdiff was 1.1 (12.5) mmHg systolic and 2.3 (6.1) mmHg diastolic, respectively. Mean self-recorded BP was 131.5 (14.1) mmHg systolic and 73.8 (7.6) mmHg diastolic, respectively. Mean morning and evening home BPs were 133.1 (16.5) versus 132 (15.7) systolic and 75.8 (8.4) versus 73.5 (8.2) diastolic, respectively. Significant beta-coefficient values were found in systolic MEdiff for age and smoking and in diastolic MEdiff for age, smoking, total cholesterol, and calcium-channel blockers. Conclusions. In a cohort of Argentine medicated patients, older age, smoking, total cholesterol, and use of calcium channel blockers were independent determinants of home-based MEdiff.

Background: Masked hypertension (MH) entails an increased cardiovascular risk. Therefore, it is important to identify those individuals who would benefit the most from out-of-office blood pressure (BP) measurement. We sought to determine the prevalence and identify predictors of MH among adult hypertensive patients under treatment., Methods: Treated hypertensive patients aged ≥ 18 years underwent office (duplicate sitting and standing BP in 1 visit) and home BP measurements (duplicate measurements for 4 days in the morning, afternoon, and evening; at least 16 measurements) and completed a questionnaire regarding risk factors and history of cardiovascular disease. MH was defined as normal office BP (<140/90mm Hg) with elevated home BP (≥135/85mm Hg, average of all readings discarding first day measurements). Patients with a systolic BP rise upon standing ≥5mm Hg were considered to have orthostatic hypertension (OHT). Variables indentified as relevant predictors of MH were entered into a multivariable logistic regression analysis model., Results: Three hundred and four patients were included (mean age = 66.7 ±13.8; 67.4% women). The prevalence of MH in the whole population was 12.4% and was 20.9% among patients with office-controlled hypertension. Factors independently associated with MH were age (odds ratio (OR) = 1.08, 95% confidence interval (CI) = 1.03-1.14), high-normal office systolic BP (OR = 5.61, 95% CI = 1.39-22.57), history of peripheral artery disease (PAD) (OR = 8.83, 95% CI = 1.5-51.84), moderate alcohol consumption (OR = 0.08, 95% CI = 0.01-0.73), and OHT (OR = 3.65, 95% CI = 1.27 to 10.51)., Conclusions: Easily measurable parameters such as age, office systolic BP, history of PAD, and OHT may help to detect a population at risk of MH that would benefit from home BP monitoring.

We assessed prevalence and clinical characteristics of resistant hypertension (RH) and prevalence of false RH (white-coat effect [WCE] by home blood pressure [BP] monitoring), among a population of 302 treated hypertensive patients, mean age 66.6 (± 13.8), 67.5% women. Resistant hypertension was defined according to the American Heart Association criteria. Prevalence of RH was 10%, and the following five variables were independently associated with it: body mass index, diabetes, isolated systolic hypertension, orthostatic hypotension, and use of beta-blockers. Prevalence of WCE among subjects with office-RH was 27.6%. Our study identified easily measurable parameters related to RH. Standing BP should be systematically measured in individuals with RH.

The present article reviews the epidemiology, pathogenesis, clinical features, diagnosis, and treatment of ankylosing spondylitis and its association with ocular changes. The authors used the PubMed (MEDLINE), LILACS, and Ophthalmology Library databases. Ankylosing spondylitis is a chronic inflammatory disease that usually affects the axial skeleton and can progress to stiffness and progressive functional limitation. Ankylosing spondylitis usually begins around the second to third decade of life, preferentially in HLA-B27-positive white males. Its etiology and pathogenesis are not completely understood, and its diagnosis is difficult. Clinical control and treatment are frequently satisfactory. Acute anterior uveíte is the most common extra-articular manifestation, occurring in 20%-30% of the patients with ankylosing spondylitis. Approximately half of the acute anterior uveíte cases are associated with the presence of the HLA-B27 antigen. It can be the first manifestation of an undiagnosed rheumatic disease, usually having a good prognosis and appropriate response to treatment. In conclusion, for better assessment and treatment of patients with uveitis, ophthalmologists and rheumatologists should work together.

Biological processes in arid communities are associated with episodic precipitation pulses. We postulate that annual to decadal-scale precipitation pulses modulate the dynamics of the intermontane Prepuna woodlands. To study this hypothesis, we have assessed the influence of precipitation pulses on the rates of growth and survival of Prosopis ferox in the Prepuna woodlands during the past century. Tree ages from several P. ferox stands were used to reconstruct the establishment patterns at each sampling site. Ring-width chronologies provided the basis to assess the influence of annual versus multiannual precipitation pulses on radial growth and establishment over time. Both the radial growth and the stand dynamics of P. ferox at the regional scale were found to be largely modulated by climate, with precipitation the dominant factor influencing interannual variations in P. ferox ring-widths. Our analysis of dendrochronological dating data on 885 individuals of P. ferox revealed a period of abundant establishment from the mid-1970s to beginning of 1990 s, which is coincident with an interval of remarkable above-average precipitation. However, tree-growth and establishment patterns at the local scale in the Prepuna also reflected land-use changes, particularly long-term variations in livestock intensity. The P. ferox dynamics documented here substantiates the hierarchical concept of "resource-pulse" in dry ecosystems, with precipitation pulses of different lengths modulating distinct dynamic processes in the P. ferox woodlands. Interannual variations in precipitation influence year-to-year patterns of P. ferox radial growth, whereas multiannual oscillations in rainfall influence episodic events of tree establishment. The long-term interval considered in this study enabled us to disentangle the roles of natural versus human controls on P. ferox dynamics in the region.