Comparing the Use of Topical Therapy Along with Anti-IL-17 and Anti-IL-23 to Treat Moderate-to-Severe Psoriasis in the Routine Clinical Practice. / Comparación del uso de la terapia tópica combinada con anti-interleucina-17 y anti-interleucina-23 en la psoriasis moderada grave en la práctica clínica.

BACKGROUND: Combinations of topical (TT) and biological therapies (BT) are a common thing in the routine clinical practice. However, the scientific medical literature on how TT is, actually, used after the initiation of BT is scarce, particularly in combination with anti-IL17, or anti-IL23. OBJECTIVES: To describe the frequency of the concomitant use of TT + BT at baseline and after a 6-month course of several drugs (anti-IL17, ustekinumab, and anti-IL23). Our secondary endpoints are to describe the type of topical therapy used, compare the frequency of use of TT among the different groups of BT, describe the survival of topical therapy in these patients, and identify the factors that can impact the use or discontinuation of topical therapy in these patients (clinical response, quality of life, type of drug, etc.). MATERIALS AND METHODS: This was a retrospective, observational, and single-center study of patients with moderate-to-severe psoriasis treated with anti-IL17 (secukinumab, ixekizumab), anti-IL17R (brodalumab), ustekinumab, and guselkumab from January 2015 through December 2020. RESULTS: We included a total of 138 patients. When treatment started, 82.7% were on TT (55% daily), and after 6 months, 86.6% had discontinued TT. Regarding the analysis by type of drug, at 6 months, we found that 100% of the patients with BRO had discontinued topical treatment. We did not find any significant differences in the frequency of use of TT based on the BT used during the 6-month course of treatment. The estimated mean course of TT was 4.3 months (SD, 6.7). Also, the estimated mean course of TT was significantly shorter in the group of patients who achieved PASI100 (2.8 months vs. 8.1 months). CONCLUSIONS: In our cohort, we saw a significant decrease in the frequency of use of TT at 6 months after starting BT in the routine clinical practice. This reduction occurred earlier in patients who improved their objective clinical response and quality of life.

A mathematical model of biofilm growth and spread within plant xylem: Case study of Xylella fastidiosa in olive trees.

Xylem-limited bacterial pathogens cause some of the most destructive plant diseases. Though imposed measures to control these pathogens are generally ineffective, even among susceptible taxa, some hosts can limit bacterial loads and symptom expression. Mechanisms by which this resistance is achieved are poorly understood. In particular, it is still unknown how differences in vascular structure may influence biofilm growth and spread within a host. To address this, we developed a novel theoretical framework to describe biofilm behaviour within xylem vessels, adopting a polymer-based modelling approach. We then parameterised the model to investigate the relevance of xylem vessel diameters on Xylella fastidiosa resistance among olive cultivars. The functionality of all vessels was severely reduced under infection, with hydraulic flow reductions of 2-3 orders of magnitude. However, results suggest wider vessels act as biofilm incubators; allowing biofilms to develop over a long time while still transporting them through the vasculature. By contrast, thinner vessels become blocked much earlier, limiting biofilm spread. Using experimental data on vessel diameter distributions, we were able to determine that a mechanism of resistance in the olive cultivar Leccino is a relatively low abundance of the widest vessels, limiting X. fastidiosa spread.

Human plasmacytoid dendritic cells express the functional purinergic halo (CD39/CD73).

Plasmacytoid dendritic cells (pDCs) are a specialized DC subset mainly associated with sensing viral pathogens and high-type I interferon (IFN-I) release in response to toll-like receptor (TLR)-7 and TLR-9 signaling. Currently, pDC contribution to inflammatory responses is extensively described; nevertheless, their regulatory mechanisms require further investigation. CD39 and CD73 are ectoenzymes driving a shift from an ATP-proinflammatory milieu to an anti-inflammatory environment by converting ATP to adenosine. Although the regulatory function of the purinergic halo CD39/CD73 has been reported in some immune cells like regulatory T cells and conventional DCs, its presence in pDCs has not been examined. In this study, we uncover for the first time the expression and functionality of the purinergic halo in human blood pDCs. In healthy donors, CD39 was expressed in the cell surface of 14.0 ± 12.5% pDCs under steady-state conditions, while CD73 showed an intracellular location and was only expressed in 8.0 ± 2.2% of pDCs. Nevertheless, pDCs stimulation with a TLR-7 agonist (R848) induced increased surface expression of both molecules (43.3 ± 23.7% and 18.6 ± 9.3%, respectively), as well as high IFN-α secretion. Furthermore, exogenous ATP addition to R848-activated pDCs significantly increased adenosine generation. This effect was attributable to the superior CD73 expression and activity because blocking CD73 reduced adenosine production and improved pDC allostimulatory capabilities on CD4 + T cells. The functional expression of the purinergic halo in human pDCs described in this work opens new areas to investigate its participation in the regulatory pDC mechanisms in health and disease.

Simplifying two-vector mechanics calculations for challenging tooth movements.

The purpose of this article was to describe a simple graphical driven method for determining the necessary two-vector mechanics (TVM) as an alternative solution to the ideal or single force. In orthodontics, some tooth movements are difficult to achieve, mainly because of the impossibility of getting the point of application for the necessary force system. Given two points in biomechanically accessible areas, adding together two vectors applied to those points will result in an equivalent force system. The method was developed based on previous research, 3,880 hypothetical cases were analyzed to determine the trends between the resulting forces and their relative locations. A graphical driven TVM method (GTVM) for establishing the necessary TVM is presented in a manner that combine different procedures from the traditional method that simplify the analysis and may allow the user to perform more complex orthodontic cases making easier to compare systems of force equivalents.

Stress distribution for mandibular extra-alveolar anchorage at different angles and force magnitudes: a finite element study.

The aim of this study was to evaluate the stress distribution in cortical and cancellous bones and within the screw when a stainless steel extra-alveolar screw (EA-S) is inserted into the retromolar region of the mandible using the finite element method (FEM). The stress values in the EA-S were highest at 60° with horizontal (shear) force and lowest at 90° with axial force. In the bones (cortical and cancellous), the stress value was greatest at 90° with horizontal force. Greater stability of the screw may be achieved by tilting it to the force when horizontal loads are applied.

Effect of the buccal fat pad in the prevention of zygomatic implant surgery postoperative complications: A pilot study.

BACKGROUND: Zygomatic implants have been used to treat severe atrophy maxilla. Since its description, the technique has been improved in order to reduce patient morbidity as well as prosthesis rehabilitation time. Despite the improvements in the procedure, zygomatic implant treatments still have complications related to the peri-implant soft-tissue; a probing depth greater than 6 millimeter (mm) and a prevalence of bleeding on probing of 45% have been described. The mobilization of the buccal fat has been used to manage different oral and maxillofacial soft-tissue pathologies. The aim of this study was to assess whether the buccal fat pad might prevent mucosal dehiscence and avoid potential postoperative complications when is placed covering the body part of the zygomatic implants. MATERIAL AND METHODS: In this pilot study, 7 patients were enrolled and a total of 28 zygomatic implants were placed and evaluated during a 12-month follow-up period. Surgical sites were randomly divided into two groups before implant placement: control group (A; in which no buccal fat pad was applied) and experimental group (B). Peri-implant soft tissue thickness difference, pain using a Visual Analog Scale (VAS), swelling, hematoma, buccal soft tissue healing and sinusitis, were evaluated. The implant survival rate was determined according the Aparicio success criteria and compared between the control and experimental procedure. RESULTS: A nonstatistical difference was found between groups regarding to pain. The experimental group showed higher soft-tissues thickness (p= 0.03) and the implant survival rate was 100% in both groups. CONCLUSIONS: The mobilization of the buccal fat pad to cover the body of the zygomatic implants increases peri-implant soft-tissue thickness, without increasing the postoperative pain.

Ocular Biomechanics and Glaucoma.

Biomechanics is a branch of biophysics that deals with mechanics applied to biology. Corneal biomechanics have an important role in managing patients with glaucoma. While evidence suggests that patients with thin and stiffer corneas have a higher risk of developing glaucoma, it also influences the accurate measurement of intraocular pressure. We reviewed the pertinent literature to help increase our understanding of the biomechanics of the cornea and other ocular structures and how they can help optimize clinical and surgical treatments, taking into consideration individual variabilities, improve the diagnosis of suspected patients, and help monitor the response to treatment.

Splicing accuracy varies across human introns, tissues and age.

Alternative splicing impacts most multi-exonic human genes. Inaccuracies during this process may have an important role in ageing and disease. Here, we investigated mis-splicing using RNA-sequencing data from ~14K control samples and 42 human body sites, focusing on split reads partially mapping to known transcripts in annotation. We show that mis-splicing occurs at different rates across introns and tissues and that these splicing inaccuracies are primarily affected by the abundance of core components of the spliceosome assembly and its regulators. Using publicly available data on short-hairpin RNA-knockdowns of numerous spliceosomal components and related regulators, we found support for the importance of RNA-binding proteins in mis-splicing. We also demonstrated that age is positively correlated with mis-splicing, and it affects genes implicated in neurodegenerative diseases. This in-depth characterisation of mis-splicing can have important implications for our understanding of the role of splicing inaccuracies in human disease and the interpretation of long-read RNA-sequencing data.

Mistaking plastic for zooplankton: Risk assessment of plastic ingestion in the Mediterranean sea.

Floating plastic debris is a pervasive pollutant in seas and oceans, affecting a wide range of animals. In particular, microplastics (<5 mm in size) increase the possibility that marine species consume plastic and enter the food chain. The present study investigates this potential mistake between plastic debris and zooplankton by calculating the plastic debris to zooplankton ratio over the whole Mediterranean Sea. To this aim, in situ data from the Tara Mediterranean Expedition are combined with environmental and Lagrangian diagnostics in a machine learning approach to produce spatially-explicit maps of plastic debris and zooplankton abundance. We then analyse the plastic to zooplankton ratio in regions with high abundances of pelagic fish. Two of the major hotspots of pelagic fish, located in the Gulf of Gabès and Cilician basin, were associated with high ratio values. Finally, we compare the plastic to zooplankton ratio values in the Pelagos Sanctuary, an important hotspot for marine mammals, with other Geographical Sub-Areas, and find that they were among the larger of the Western Mediterranean Sea. Our results indicate a high potential risk of contamination of marine fauna by plastic and advocate for novel integrated modelling approaches which account for potential trophic transfer within the food chain.

Implante de dexametasona antes de tratamiento anti-VEGF en desprendimientos del epitelio pigmentario secundarios a degeneración macular asociada a la edad con características de alto riesgo de rotura / Dexamethasone implant prior to anti-VEGF therapy in pigment epithelium detachments with high-risk rupture characteristics secondary to neovascular age-related macular degeneration

Objetivo Evaluar la incidencia de desgarro del epitelio pigmentario cuando se administra un implante intravítreo de dexametasona de liberación retardada (uso off-label) previo al tratamiento antiangiogénico en desprendimientos del epitelio pigmentario (DEP) secundarios a degeneración macular neovascular asociada a la edad (DMAEn) con características de alto riesgo de rotura e investigar si provoca una disminución del tamaño del DEP. Métodos Se incluyeron pacientes con DMAEn, altura del DEP >500micras e implante de Ozurdex previo a la terapia antiangiogénica. Se registró la presencia de rotura del epitelio pigmentario en tomografías de coherencia óptica, agudeza visual mejor corregida (AVMC) y medidas del DEP (altura y diámetro máximos). Resultados El estudio incluyó a 14 ojos de 14 pacientes: edad media 77±7 años, 11 (79%) mujeres. 25±13 días después del Ozurdex los pacientes comenzaron con al menos 3 inyecciones mensuales de anti-VEGF. La AVMC mejoró de 64±14 a 69±11 letras después de la terapia anti-VEGF (p>0,05). La altura media inicial del DEP fue de 817±269μm, siendo 639±268μm después de Ozurdex y 370±260μm después de las inyecciones de anti-VEGF (p=0,035 y p=0,009). Se produjo un desgarro del epitelio pigmentario de la retina (7%). No se hallaron otros efectos adversos. Conclusione El implante de dexametasona antes de la terapia anti-VEGF puede representar una modalidad terapéutica prometedora para los DEP grandes en la DMAEn, reduciendo las dimensiones del DEP y el riesgo de desgarros del epitelio pigmentario antes de la terapia anti-VEGF (AU)

Objective Evaluate the incidence of pigment epithelial tear when intravitreal delayed-release dexamethasone implant is administered (off-label use) prior to antiangiogenic treatment in pigment epithelium detachments (PED) secondary to neovascular age-related macular degeneration (nAMD) with high-risk rupture characteristics and investigate if it causes a decrease in the PED size. Methods Patients with nAMD, PED height >500microns and Ozurdex implant prior to the antiangiogenic therapy were included. The presence of pigment epithelium rupture in optical coherence tomography scans, best-corrected visual acuity (BCVA) and PED measurements (maximum height and diameter) were registered. Results The study included 14 eyes of 14 patients: mean age 77±7 years, 11 (79%) females. 25±13 days after the Ozurdex, patients started with at least 3 anti-VEGF monthly injections. BCVA improved from 64±14 to 69±11 letters after anti-VEGF therapy (P>.05). Mean baseline PED height was 817±269μm, being 639±268μm after Ozurdex and 370±260μm after anti-VEGF injections (P=.035 and P=.009). One retinal pigment epithelium tear occurred (7%). No other adverse effects were reported. Conclusions Dexamethasone implant prior to anti-VEGF therapy may represent a promising therapeutic modality for large PED in nAMD, reducing PED dimensions and the risk of pigment epithelium tears prior to anti VEGF therapy (AU)

SARC-F and SARC-CalF Scores as Mortality Risk Factors in Older Men with Cancer: A Longitudinal Study from Peru.

OBJECTIVES: We aimed to evaluate the role of SARC-F and SARC-CalF scores as risk factors for mortality in adults over 60 years of age with cancer of the Centro Médico Naval (CEMENA) in Callao, Peru during 2012-2015. METHODS: We performed a secondary analysis of data from a prospective cohort carried out from September 2012 to February 2013 in the Geriatrics Department of CEMENA. The outcome variable was mortality at two years of follow-up, while the exposure variable was the risk of sarcopenia assessed using the SARC-F and SARC-CalF scales. We carried out Cox proportional-hazards models to assess the role of SARC-F and SARC-CalF scores as risk factors for mortality. We estimated crude (cHR) and adjusted (aHR) hazard ratios (HR) with their respective 95% confidence intervals (95%CI). Likewise, we calculated the area under the curve (AUC) of both exposure variables in relation to mortality. RESULTS: We analyzed data from 922 elderly men with cancer; 43.1% (n=397) were between 60 and 70 years old. 21.5% (n=198) and 45.7% (n=421) were at risk of sarcopenia according to SARC-F and SARC-CalF, respectively, while the incidence of mortality was 22.9% (n=211). In the adjusted Cox regression model, we found that the risk of sarcopenia measured by SARC-F (aHR=2.51; 95%CI: 1.40-2.77) and SARC-CalF (aHR=2.04; 95%CI: 1.55-4.02) was associated with a higher risk of death in older men with cancer. In the diagnostic performance analysis, we found that the AUC for mortality prediction was 0.71 (95%CI: 0.68-0.75) for SARC-F and 0.80 (95%CI: 0.78-0.82) for SARC-CalF. CONCLUSIONS: The risk of sarcopenia evaluated by SARC-F and SARC-CalF scores was associated with an increased risk of mortality in older men with cancer. Both scales proved to be useful and accessible instruments for the identification of groups at risk of mortality.

A 3D image-based modelling approach for understanding spatiotemporal processes in phosphorus fertiliser dissolution, soil buffering and uptake by plant roots.

Phosphorus (P) is a key yield-limiting nutrient for crops, but the main source of P fertiliser is finite. Therefore, efficient fertilisation is crucial. Optimal P application requires understanding of the dynamic processes affecting P availability to plants, including fertiliser dissolution rate and soil buffer power. However, standard soil testing methods sample at fixed time points, preventing a mechanistic understanding of P uptake variability. We used image-based modelling to investigate the effects of fertiliser dissolution rate and soil buffer power on P uptake by wheat roots imaged using X-ray CT. We modelled uptake based on 1-day, 1-week, and 14-week dissolution of a fixed quantity of total P for two common soil buffer powers. We found rapid fertiliser dissolution increased short-term root uptake, but total uptake from 1-week matched 1-day dissolution. We quantified the large effects root system architecture had on P uptake, finding that there were trade-offs between total P uptake and uptake per unit root length, representing a carbon investment/phosphorus uptake balance. These results provide a starting point for predictive modelling of uptake from different P fertilisers in different soils. With the addition of further X-ray CT image datasets and a wider range of conditions, our simulation approach could be developed further for rapid trialling of fertiliser-soil combinations to inform field-scale trials or management.

Impact of root hairs on microscale soil physical properties in the field.

Aims: Recent laboratory studies revealed that root hairs may alter soil physical behaviour, influencing soil porosity and water retention on the small scale. However, the results are not consistent, and it is not known if structural changes at the small-scale have impacts at larger scales. Therefore, we evaluated the potential effects of root hairs on soil hydro-mechanical properties in the field using rhizosphere-scale physical measurements. Methods: Changes in soil water retention properties as well as mechanical and hydraulic characteristics were monitored in both silt loam and sandy loam soils. Measurements were taken from plant establishment to harvesting in field trials, comparing three barley genotypes representing distinct phenotypic categories in relation to root hair length. Soil hardness and elasticity were measured using a 3-mm-diameter spherical indenter, while water sorptivity and repellency were measured using a miniaturized infiltrometer with a 0.4-mm tip radius. Results: Over the growing season, plants induced changes in the soil water retention properties, with the plant available water increasing by 21%. Both soil hardness (P = 0.031) and elasticity (P = 0.048) decreased significantly in the presence of root hairs in silt loam soil, by 50% and 36%, respectively. Root hairs also led to significantly smaller water repellency (P = 0.007) in sandy loam soil vegetated with the hairy genotype (-49%) compared to the hairless mutant. Conclusions: Breeding of cash crops for improved soil conditions could be achieved by selecting root phenotypes that ameliorate soil physical properties and therefore contribute to increased soil health. Supplementary Information: The online version contains supplementary material available at 10.1007/s11104-022-05530-1.

Dexamethasone implant prior to anti-VEGF therapy in pigment epithelium detachments with high-risk rupture characteristics secondary to neovascular age-related macular degeneration.

OBJECTIVE: Evaluate the incidence of pigment epithelial tear when intravitreal delayed-release dexamethasone implant is administered (off-label use) prior to antiangiogenic treatment in pigment epithelium detachments (PED) secondary to neovascular age-related macular degeneration (nAMD) with high-risk rupture characteristics and investigate if it causes a decrease in the PED size. METHODS: Patients with nAMD, PED height >500 microns and Ozurdex implant prior to the antiangiogenic therapy were included. The presence of pigment epithelium rupture in optical coherence tomography scans, best-corrected visual acuity (BCVA) and PED measurements (maximum height and diameter) were registered. RESULTS: The study included 14 eyes of 14 patients: mean age 77 ±â€¯7 years, 11 (79%) females. 25 ±â€¯13 days after the Ozurdex, patients started with at least 3 anti-VEGF monthly injections. BCVA improved from 64 ±â€¯14-69 ±â€¯11 letters after anti-VEGF therapy (p > 0.05). Mean baseline PED height was 817 ±â€¯269 µm, being 639 ±â€¯268 µm after Ozurdex and 370 ±â€¯260 µm after anti-VEGF injections (p = 0.035 and p = 0.009). One retinal pigment epithelium tear occurred (7%). No other adverse effects were reported. CONCLUSIONS: Dexamethasone implant prior to anti-VEGF therapy may represent a promising therapeutic modality for large PED in nAMD, reducing PED dimensions and the risk of pigment epithelium tears prior to anti VEGF therapy.

Normative Data for Brainstem Structures, the Midbrain-to-Pons Ratio, and the Magnetic Resonance Parkinsonism Index.

BACKGROUND AND PURPOSE: Imaging biomarkers derived from different brainstem structures are suggested to differentiate among parkinsonian disorders, but clinical implementation requires normative data. The main objective was to establish high-quality, sex-specific data for relevant brainstem structures derived from MR imaging in healthy subjects from the general population in their sixth and seventh decades of life. MATERIALS AND METHODS: 3D T1WI acquired on the same 1.5T scanner of 996 individuals (527 women) between 50 and 66 years of age from a prospective population study was used. The area of the midbrain and pons and the widths of the middle cerebellar peduncles and superior cerebellar peduncles were measured, from which the midbrain-to-pons ratio and Magnetic Resonance Parkinsonism Index [MRPI = (Pons Area / Midbrain Area) × (Middle Cerebellar Peduncles / Superior Cerebellar Peduncles)] were calculated. Sex differences in brainstem measures and correlations to age, height, weight, and body mass index were investigated. RESULTS: Inter- and intrareliability for measuring the different brainstem structures showed good-to-excellent reliability (intraclass correlation coefficient = 0.785-0.988). There were significant sex differences for the pons area, width of the middle cerebellar peduncles and superior cerebellar peduncles, midbrain-to-pons ratio, and MRPI (all, P < .001; Cohen D = 0.44-0.98), but not for the midbrain area (P = .985). There were significant very weak-to-weak correlations between several of the brainstem measures and age, height, weight, and body mass index in both sexes. However, no systematic difference in distribution caused by these variables was found, and because age had the highest and most consistent correlations, age-/sex-specific percentiles for the brainstem measures were created. CONCLUSIONS: We present high-quality, sex-specific data and age-/sex-specific percentiles for the mentioned brainstem measures. These normative data can be implemented in the neuroradiologic work-up of patients with suspected brainstem atrophy to avoid the risk of misdiagnosis.