Lessons on protein structure from interleukin-4: All disulfides are not created equal.

Interleukin-4 (IL-4) is a hematopoietic cytokine composed by a four-helix bundle stabilized by an antiparallel beta-sheet and three disulfide bonds: Cys3-Cys127, Cys24-Cys65, and Cys46-Cys99. IL-4 is involved in several immune responses associated to infection, allergy, autoimmunity, and cancer. Besides its physiological relevance, IL-4 is often used as a "model" for protein design and engineering. Hence, to understand the role of each disulfide in the structure and dynamics of IL-4, we carried out several spectroscopic analyses (circular dichroism [CD], fluorescence, nuclear magnetic resonance [NMR]), and molecular dynamics (MD) simulations on wild-type IL-4 and four IL-4 disulfide mutants. All disulfide mutants showed loss of structure, altered interhelical angles, and looser core packings, showing that all disulfides are relevant for maintaining the overall fold and stability of the four-helix bundle motif, even at very low pH. In the absence of the disulfide connecting both protein termini Cys3-Cys127, C3T-IL4 showed a less packed protein core, loss of secondary structure (~9%) and fast motions on the sub-nanosecond time scale (lower S2 order parameters and larger τc correlation time), especially at the two protein termini, loops, beginning of helix A and end of helix D. In the absence of Cys24-Cys65, C24T-IL4 presented shorter alpha-helices (14% loss in helical content), altered interhelical angles, less propensity to form the small anti-parallel beta-sheet and increased dynamics. Simultaneously deprived of two disulfides (Cys3-Cys127 and Cys24-Cys65), IL-4 formed a partially folded "molten globule" with high 8-anilino-1-naphtalenesulphonic acid-binding affinity and considerable loss of secondary structure (~50%decrease), as shown by the far UV-CD, NMR, and MD data.

Impact of Coronary Artery Calcium Score Screening on Cardiovascular Risk Stratification of Patients with Atrial Fibrillation Undergoing Ablation.

INTRODUCTION: There is a well-established association between atrial fibrillation (AF) and coronary artery disease. Coronary artery calcium score (CACS) is a helpful tool to refine cardiovascular (CV) risk stratification and inform on the best strategies for primary CV prevention. This study aims to evaluate the impact of opportunistic screening with CACS on risk stratification and decision of preventive therapies, in patients with AF. METHODS: Cross-sectional study including patients with AF or atrial flutter undergoing cardiac computed tomography for ablation procedure planning, from 2017 to 2019. Baseline clinical and demographical data were collected. CACS was assessed in patients without coronary artery disease using the Agatston method. RESULTS: A total of 474 patients were included (93% with AF, mean age of 58 ± 10 years, 62% male). CACS >0 was present in 254 (54%) patients. According to CACS and the Society of Cardiovascular Computed Tomography recommendations, 25% of the patients would be candidates for statin therapy and 17% would be candidates for changes in the current statin intensity; in 11 patients (8%), acetylsalicylic acid would be recommended. CONCLUSION: In our study, more than half of the patients undergoing cardiac computed tomography before AF catheter ablation had CACS above zero. Our findings suggest that an opportunistic evaluation of CACS at the time of ablation can be an important tool to improve CV risk stratification, with important clinical and therapeutic implications.

Sensor Integration in a Forestry Machine.

This paper presents the integration of multimodal sensor systems for an autonomous forestry machine. The utilized technology is housed in a single enclosure which consolidates a set of components responsible for executing machine control actions and comprehending its behavior in various scenarios. This sensor box, named Sentry, will subsequently be connected to a forestry machine from MDB, model LV600 PRO. The article outlines previous work in this field and then details the integration and operation of the equipment, integrated into the forest machine, providing descriptions of the adopted architecture at both the hardware and software levels. The gathered data enables the assessment of the forestry machine's orientation and position based on the information collected by the sensors. Finally, practical experiments are presented to demonstrate the system's behavior and to analyze the methods to be employed for autonomous navigation, thereby assessing the performance of the established architecture. The novel aspects of this work include the physical and digital integration of a multimodal sensor system on a forestry machine, its use in a real case scenario, namely, forest vegetation removal, and the strategies adopted to improve the machine localization and navigation performance on unstructured environments.

Exploring the Impact of Covid-19-Related Perceptions on Psychological Distress and Quality of Life in an International Gastrointestinal Cohort Over Time Guided by the Common Sense Model.

The aim of this longitudinal study was to examine changes in COVID-19 and illness-related perceptions, gastrointestinal symptoms, coping, catastrophising, psychological distress, and QoL during the COVID-19 pandemic. A total of 831 adults with a gastrointestinal condition completed an online questionnaire at baseline (May-October 2020). Of those, 270 (32.5%) participants (85.2% female, mean age = 47.3 years) provided follow-up data (March-May 2021). Repeated-measures multiple analysis of variance and a cross-lagged panel model were used to test the study hypotheses. Gastrointestinal symptoms and COVID-19 perceptions at follow-up were strongly predicted by their baseline values, while illness perceptions were predicted by baseline gastrointestinal symptoms. Cross-lagged relationships indicated a reciprocal relationship between gastrointestinal symptoms and psychological distress. Moreover, gastrointestinal symptoms had substantial predictive utility, strongly predicting future gastrointestinal symptoms, and to a lesser extent, more negative illness perceptions, greater psychological distress, and greater use of adaptive coping strategies across time.

Improved Clinical Outcomes After Lateralized Reverse Shoulder Arthroplasty: A Systematic Review.

BACKGROUND: Lateralized reverse shoulder arthroplasty (RSA) has emerged as an attempt to improve on some of the drawbacks of conventional RSA, such as glenoid notching and decrease in ROM. Although this new design is being used in clinical practice, the evidence is mostly limited to case series and has not been systematically reviewed. QUESTIONS/PURPOSES: (1) How much did patient-reported outcome measures (PROMs) and ROM improve among patients who receive a lateralized RSA implant? (2) What proportion of shoulders experience complications, revision surgery, or scapular notching? METHODS: The PubMed and EMBASE databases were searched from database inception to January 31, 2020. We included clinical studies that reported the PROMs and/or ROM of patients with insufficient rotator cuffs undergoing RSA with a lateralized implant. All other types of studies and those including patients with fractures, instability or escape, infection, rheumatologic disease, neurologic disease, or revision surgeries as an indication for RSA were excluded. PROMs and ROM were collected and are reported as mean values and ranges. Complications, revision surgery, and scapular notching are presented as proportions. The percentage of the mean change relative to the minimum clinically important difference (MCID) was calculated using the anchor-based value for each outcome. The Methodological Index for Non-randomized Studies (MINORS) was used to assess study quality. The initial search yielded 678 studies; 61 full-text articles were analyzed according to our eligibility criteria. After a detailed analysis, we included nine studies that evaluated 1670 patients (68% of whom [1130] were women) with a mean age of 71.8 ± 0.6 years. The mean follow-up period was 41.1 ± 5.6 months. The mean MINORS score was 12 ± 4. RESULTS: Active ROM improved for forward flexion (mean change 47° to 82°; MCID 12°), abduction (mean change 43° to 80°; MCID 7°), external rotation (mean change 8° to 39°; MCID 3°), and internal rotation (mean change -2 to 1 points). PROM scores also improved, including the American Shoulder and Elbow Surgeons score (mean change 20 to 50; MCID 20.9 points), Constant score (mean change 28 to 40; MCID 5.7 points), Simple Shoulder Test score (mean change 3 to 7; MCID 2.4 points), and VAS score (mean change -1.8 to -4.9; MCID -1.6 points). The proportion of shoulders with complications ranged from 0% (0 of 44) to 21% (30 of 140), and the proportion of shoulders with scapular notching ranged from 0% (0 of 76) to 29% (41 of 140). The proportion of patients undergoing revision ranged from 0% (0 of 44) to 13% (10 of 76) at short-term follow-up. CONCLUSION: Lateralized RSA is a reasonable alternative to medialized implants for patients with rotator cuff insufficiency because it might reduce the likelihood of scapular notching without apparently compromising PROMs or ROM. More studies are required to determine whether there is a direct correlation between the amount of lateralization and PROMs or ROM.

Electrically Conductive and Antimicrobial Agro-Food Waste Biochar Functionalized with Zinc Oxide Particles.

Carbonaceous materials derived from biomass have been used as sustainable platforms for the growth of ZnO particles aiming the production of functional composite fillers. Kidney-bean pods were pyrolyzed by applying an experimental design that demonstrates that the specific surface area (SBET) of biochar is improved with increasing pyrolysis temperature combined with a short air-oxidation time. Meanwhile, the graphitization degree and the electrical conductivity (EC) of biochars were negatively affected by increasing the air-oxidation time. The biochar sample with the higher EC and the one with the higher SBET were selected to be functionalized with ZnO particles by a solvothermal methodology, obtaining composites with an EC and SBET properties superior to the ZnO-rGO composite, in addition to a similar antibacterial activity. The developed ZnO-biochar composite structures, which are more ecological and biocompatible than the ZnO composites derived from graphene sheets, can be applied as electrically conductive and active fillers.

Extending the Common Sense Model to Explore the Impact of the Fear of COVID-19 on Quality of Life in an International Inflammatory Bowel Disease Cohort.

The aim of this cross-sectional study was to use an extended common sense model (CSM) to evaluate the impact of fear of COVID-19 on quality of life (QoL) in an international inflammatory bowel disease cohort. An online study involving 319 adults (75% female, mean (SD) 14.06 (15.57) years of symptoms) completed the Gastrointestinal Symptom Rating Scale, Brief Illness Perceptions Questionnaire, Fear of Contracting COVID-19 Scale, Brief-COPE, Depression, Anxiety and Stress Scale, and the EUROHIS-QOL. The extended CSM had an excellent fit (χ2 (9) = 17.06, p = .05, χ2/N = 1.90, RMSEA = 0.05, SRMR = 0.04, CFI = .99, TLI = .97, GFI = 0.99), indicating the influence of gastrointestinal symptoms on QoL was mediated by illness perceptions, fear of COVID-19, adaptive and maladaptive coping, and psychological distress. Interventions targeting the fear of COVID-19 in the context of an individual's perceptions will likely enhance QoL during the pandemic.

Exploring the Relationship Between Self-Isolation and Distress Among People with Gastrointestinal Disorders During the COVID-19 Pandemic.

This study aimed to explore the association between perceived isolation and symptoms of distress in people with GI disorders at the time of the pandemic; and to examine factors which moderate this relationship. This online cross-sectional survey was advertised in May-September 2020 via patient organisations and associated social media. Overall, 831 people (82% female, mean age 49 years) from 27 countries participated. A significant relationship between social isolation and psychological distress was noted (r = .525, p < .001). GI symptoms moderated the association between isolation and distress (B = .047, t = 2.47, p = .015). Interventions targeting these factors may help to reduce distress in people with GI disorders at the time of major stressors such as the COVID-19 pandemic.

Challenges faced by university students during the COVID-19: An international study in five countries during the early phase of the pandemic.

This study focused on the specific challenges of university students in the face of the COVID-19 pandemic and examined similarities and differences in COVID-related concerns and difficulties in functioning in samples of undergraduate students in five countries. A sample of 4306 undergraduate university students (43.8% males, 56.2% females) from Israel, Kosovo, Ukraine, Cyprus and Germany participated in an anonymous online survey during the first wave of the pandemic, between March and June 2020. Study variables included the assessment of the exposure to COVID-19, perceived health status, specific COVID-related concerns and functional difficulties, social support, and the perceived level of coping. Similar concerns about the uncertainty regarding the termination of the health crisis and worry for the health of family members were identified as the most common concerns in the five countries. Challenges in online learning and financial difficulties were rated as the most central difficulties. Both COVID-related concerns and COVID-related difficulties predicted lower levels of perceived coping. Greater social support was associated with better perceived coping. Policymakers should be informed by the accumulating research showing the substantive relationships between academic difficulties and perceived COVID-related distress and coping.

Psychological flexibility and fear of recurrence in prostate cancer.

OBJECTIVE: Psychological flexibility and fear of cancer recurrence are important variables that influence psychosocial outcomes in individuals diagnosed with a range of different types of cancer. Their role and how they impact on psychological distress and quality of life in men with prostate cancer specifically have not been established. METHODS: A cross-sectional sample of 144 men with prostate cancer was recruited. Multiple regression and conditional process analysis were used to assess whether psychological flexibility moderates the relationship between fear of recurrence and distress and quality of life. RESULTS: Psychological flexibility significantly predicted psychological distress (ß = -0.56, p < 0.0001) and quality of life (ß = 0.21, p < 0.0001), appearing a stronger predictor of psychological distress than fear of recurrence (ß = 0.25, p < 0.0001). Fear of recurrence was a stronger predictor of quality of life (ß = -0.41, p < 0.0001) than psychological flexibility. Psychological flexibility moderated the relationship between fear of recurrence and psychological distress (ß = -0.01, p < 0.001). At low and average levels of psychological flexibility, psychological distress mediated the relationship between fear of recurrence and quality of life (ß = -0.33 to -0.16, p < 0.05). At high levels of psychological flexibility, distress no longer mediated this relationship (ß = 0.01, ns), supporting the role of psychological flexibility as a moderator. CONCLUSIONS: These findings suggest that psychological flexibility might be a useful treatment target, through interventions such as Acceptance and Commitment Therapy, to buffer the effects of fear of recurrence and distress and improve psychosocial outcomes in this population.

Design of Alginate-Based Bionanocomposites with Electrical Conductivity for Active Food Packaging.

Bionanocomposite materials have been designed as a promising route to enhance biopolymer properties, especially for food packaging application. The present study reports the preparation of bionanocomposite films of alginate with different loadings of pure reduced graphene oxide (rGO) or of mixed zinc oxide-rGO (ZnO-rGO) fillers by solvent casting. Sepiolite is used to make compatible rGO with the hydrophilic matrix. The addition of fillers to alginate matrix maintains the low water solubility promoted by the calcium chloride treatment, and, additionally, they demonstrate a weaker mechanical properties, and a slight increase in water vapor permeability and wettability. Due to the properties of ZnO-rGO, the alginate bionanocomposites show an increase of electrical conductivity with the increase of filler content. While the highest electrical conductivity (0.1 S/m) is achieved by the in-plane measurement, it is in the through-plane measurement the remarkable enhancement of almost 30 times greater than the alginate film. With 50% of ZnO-rGO filler, the bionanocomposites present the highest antioxidant and antibacterial activities. The combination of electrical conductivity with bioactive properties makes these films promising not only to extend food shelf-life but also to allow packaged food sterilization at low temperature.

Fears of compassion magnify the harmful effects of threat of COVID-19 on mental health and social safeness across 21 countries.

BACKGROUND: The COVID-19 pandemic is a massive global health crisis with damaging consequences to mental health and social relationships. Exploring factors that may heighten or buffer the risk of mental health problems in this context is thus critical. Whilst compassion may be a protective factor, in contrast fears of compassion increase vulnerability to psychosocial distress and may amplify the impact of the pandemic on mental health. This study explores the magnifying effects of fears of compassion on the impact of perceived threat of COVID-19 on depression, anxiety and stress, and social safeness. METHODS: Adult participants from the general population (N = 4057) were recruited across 21 countries worldwide, and completed self-report measures of perceived threat of COVID-19, fears of compassion (for self, from others, for others), depression, anxiety, stress and social safeness. RESULTS: Perceived threat of COVID-19 predicted increased depression, anxiety and stress. The three flows of fears of compassion predicted higher levels of depression, anxiety and stress and lower social safeness. All fears of compassion moderated (heightened) the impact of perceived threat of COVID-19 on psychological distress. Only fears of compassion from others moderated the effects of likelihood of contracting COVID-19 on social safeness. These effects were consistent across all countries. CONCLUSIONS: Fears of compassion have a universal magnifying effect on the damaging impact of the COVID-19 pandemic on mental health and social safeness. Compassion focused interventions and communications could be implemented to reduce resistances to compassion and promote mental wellbeing during and following the pandemic.

Early Repolarization Pattern and Left Ventricular Mass in Hypertrophic Cardiomyopathy.

BACKGROUND: J-point elevation in the inferior and/or lateral leads is associated with an increased incidence of sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM), although the exact underlying mechanism is not known. As severe left ventricular hypertrophy and late gadolinium enhancement (LGE) are important risk factors for SCD in this population, we aimed to assess whether there was an association between an early repolarization pattern (ERP) and greater left ventricular mass (LVM) and LGE extent among patients with HCM. METHODS: This was a retrospective cohort study of 85 consecutive patients with HCM who underwent cardiac magnetic resonance (CMR) and had an electrocardiogram without confounders (intraventricular conduction delay, complete left or right bundle branch block, or ventricular paced rhythm). Baseline characteristics and MRI-derived LVM and LGE extent were compared between patients with and without ERP. RESULTS: ERP was present in 9 out of 85 patients (10.6%). Patients with ERP had greater indexed LVM compared to those without (112.5 ± 26.3 vs. 87.8 ± 24.6 g/m2, p = 0.006). Logistic regression analysis revealed a 4.2-fold increase in the odds of prevalent ERP per standard deviation increase in body surface area-indexed LVM (odds ratio 4.2; 95% CI 1.54-11.4, p = 0.005). There were no statistically significant differences regarding LGE extent between groups. CONCLUSION: ERP is associated with greater CMR-derived LVM among patients with HCM. This finding could partially explain the association between J waves and a higher risk of SCD in this population. There were no differences in LGE extent. Further studies are needed to confirm this association and evaluate the importance of ERP as a marker of increased risk of SCD in HCM.

Impact of laser iridotomy on headache symptoms in angle-closure subjects.

BACKGROUND: Migraine symptoms are frequently referred by glaucoma patients. Although most studies analyze headache in the acute setting of angle closure, many patients with chronic occludable angles also complain of headaches. The aim of this study was to determine the impact of laser peripheral iridotomy (LPI) on the magnitude and frequency of headache symptoms in patients with occludable angles. METHODS: Prospective cohort study. Patients with indication for prophylactic LPI due to occludable iridocorneal angle were included. Headache symptoms were assessed before and at least 4 weeks after LPI using the Headache Impact Test-6 (HIT-6) questionnaire. A HIT-6 score of ≥ 50 points was labeled as a clinically significant headache. RESULTS: Thirty-one subjects were included. Prophylactic LPI was performed in 60 eyes, as 2 patients were pseudophakic in the fellow eye. Baseline HIT-6 score was 59.9 ± 11.8, with over three quarters of these patients scoring higher than 50 points (n = 24). A statistically significant reduction in HIT-6 score was found after LPI treatment (45.4 ± 7.7, p < 0.01). Sub-analysis within the clinically symptomatic subjects disclosed a significant improvement after treatment in this group (baseline, 65.3 ± 6.2 vs post-LPI 46.2 ± 8.3, p < 0.01), with a high baseline HIT-6 score being predictive of a symptomatic improvement after LPI (χ2(8) = 15.3, p = 0.001). This is mimicked from the patient's perspective, as the two subjective questions after LPI, concerning pain intensity and frequency, report that 79.2% had a statistically significant improvement of the headaches. CONCLUSIONS: Within our sample, the majority of patients with occludable angles had clinically relevant headaches. LPI provided symptomatic relief in the majority of those patients with high HIT-6 scores. Further studies are needed to explore the relationships between headache and angle anatomy.

INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUES AND OUTER RETINAL LAYER STRUCTURES.

PURPOSE: To examine the influence of the inverted flap (IF) internal limiting membrane (ILM) technique in macular hole (MH) closure on outer retinal layers after MH surgery. METHODS: Retrospective study. Postoperative position of ILM, recovery rate of external limiting membrane and ellipsoid zone, and best-corrected visual acuity were evaluated. The Inserted group, where the IF is placed inside the hole, was compared with the Cover group, where the IF completely covers the hole. RESULTS: Sixty-two eyes of 58 patients who underwent vitrectomy and ILM peeling with the IF technique for large MHs (>400 µm) with successful MH closure and a follow-up of 12 months were evaluated. In the 24 eyes of the Inserted group, there was no regeneration of external limiting membrane or ellipsoid zone after 12 months. In the 38 eyes of Cover group, external limiting membrane recovered in 55.3% of patients 1 month after surgery, and in 86.1% after 12 months. The elipsoid zone layer was present in 58% of the patients. CONCLUSION: Poorer anatomical and visual results were associated with the IF technique where ILM insertion occurs compared with ILM placed over the hole. These findings suggest that insertion of the ILM in the hole might prevent outer retinal layers realignment and visual recovery in MH surgery.

Complex Polysaccharide-Based Nanocomposites for Oral Insulin Delivery.

Polyelectrolyte nanocomposites rarely reach a stable state and aggregation often occurs. Here, we report the synthesis of nanocomposites for the oral delivery of insulin composed of alginate, dextran sulfate, poly-(ethylene glycol) 4000, poloxamer 188, chitosan, and bovine serum albumin. The nanocomposites were obtained by Ca2+-induced gelation of alginate followed by an electrostatic-interaction process among the polyelectrolytes. Chitosan seemed to be essential for the final size of the nanocomposites and there was an optimal content that led to the synthesis of nanocomposites of 400-600 nm hydrodynamic size. The enhanced stability of the synthesized nanocomposites was assessed with LUMiSizer after synthesis. Nanocomposite stability over time and under variations of ionic strength and pH were assessed with dynamic light scattering. The rounded shapes of nanocomposites were confirmed by scanning electron microscopy. After loading with insulin, analysis by HPLC revealed complete drug release under physiologically simulated conditions.

Engaging Children and Young People in Digital Mental Health Interventions: Systematic Review of Modes of Delivery, Facilitators, and Barriers.

BACKGROUND: There is a high prevalence of children and young people (CYP) experiencing mental health (MH) problems. Owing to accessibility, affordability, and scalability, an increasing number of digital health interventions (DHIs) have been developed and incorporated into MH treatment. Studies have shown the potential of DHIs to improve MH outcomes. However, the modes of delivery used to engage CYP in digital MH interventions may differ, with implications for the extent to which findings pertain to the level of engagement with the DHI. Knowledge of the various modalities could aid in the development of interventions that are acceptable and feasible. OBJECTIVE: This review aimed to (1) identify modes of delivery used in CYP digital MH interventions, (2) explore influencing factors to usage and implementation, and (3) investigate ways in which the interventions have been evaluated and whether CYP engage in DHIs. METHODS: A literature search was performed in the Cochrane Library, Excerpta Medica dataBASE (EMBASE), Medical Literature Analysis and Retrieval System Online (MEDLINE), and PsycINFO databases using 3 key concepts "child and adolescent mental health," "digital intervention," and "engagement." Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed using rigorous inclusion criteria and screening by at least two reviewers. The selected articles were assessed for quality using the mixed methods appraisal tool, and data were extracted to address the review aims. Data aggregation and synthesis were conducted and presented as descriptive numerical summaries and a narrative synthesis, respectively. RESULTS: This study identified 6 modes of delivery from 83 articles and 71 interventions for engaging CYP: (1) websites, (2) games and computer-assisted programs, (3) apps, (4) robots and digital devices, (5) virtual reality, and (6) mobile text messaging. Overall, 2 themes emerged highlighting intervention-specific and person-specific barriers and facilitators to CYP's engagement. These themes encompassed factors such as suitability, usability, and acceptability of the DHIs and motivation, capability, and opportunity for the CYP using DHIs. The literature highlighted that CYP prefer DHIs with features such as videos, limited text, ability to personalize, ability to connect with others, and options to receive text message reminders. The findings of this review suggest a high average retention rate of 79% in studies involving various DHIs. CONCLUSIONS: The development of DHIs is increasing and may be of interest to CYP, particularly in the area of MH treatment. With continuous technological advancements, it is important to know which modalities may increase engagement and help CYP who are facing MH problems. This review identified the existing modalities and highlighted the influencing factors from the perspective of CYP. This knowledge provides information that can be used to design and evaluate new interventions and offers important theoretical insights into how and why CYP engage in DHIs.

Fascia Lata Autograft Versus Human Dermal Allograft in Arthroscopic Superior Capsular Reconstruction for Irreparable Rotator Cuff Tears: A Systematic Review of Clinical Outcomes.

PURPOSE: To determine the clinical outcomes of arthroscopic superior capsular reconstruction (ASCR) using either fascia lata autograft or human dermal allograft for irreparable rotator cuff tears (IRCTs). METHODS: A systematic review was performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines by searching the MEDLINE, Embase, and Cochrane Library databases through January 31, 2019. The inclusion criteria were as follows: 5 or more consecutive patients who underwent ASCR for IRCTs; clinical outcome measures reported at a minimum follow-up of 12 months; and magnetic resonance imaging assessment at a minimum follow-up of 6 months. The methodologic quality was evaluated using the Methodological Index for Non-randomized Studies (MINORS). A narrative synthesis of data was performed. Mean outcome improvements were compared with minimal clinically important differences. RESULTS: We identified 7 eligible studies that included 344 shoulders in 338 patients who underwent ASCR for IRCTs (all Level IV studies). The mean MINORS score was 12.3 ± 1.60. Of the 7 studies, 5 had a high risk of bias (MINORS score ≤12): 2 studies using only fascia lata autograft and 3 studies using only human dermal allograft. The mean age of patients ranged from 59.4 to 66.9 years. The mean follow-up time ranged from 12 to 48 months. All studies reported statistically significant and clinically important mean improvements in active elevation (range of means, 28°-56°), the Constant score (range of means, 12-47.1 points), or the American Shoulder and Elbow Surgeons score (range of means, 29.3-56 points). In total, 218 shoulders underwent postoperative magnetic resonance imaging. The graft tear rate reported in studies using fascia lata autograft (181 shoulders) ranged from 5% to 32%, whereas the values reported in studies using human dermal allograft (37 shoulders) ranged from 20% to 75%. CONCLUSIONS: ASCR using either fascia lata autograft or human dermal allograft leads to significant and clinically important improvements in clinical outcomes in IRCT patients at 12 months or later. LEVEL OF EVIDENCE: Level IV, systematic review of Level IV studies.

Loading, release profile and accelerated stability assessment of monoterpenes-loaded solid lipid nanoparticles (SLN).

Glycerol monostearate solid lipid nanoparticles (SLN) were produced by hot high-pressure homogenization technique to load alpha-pinene, citral, geraniol or limonene. SLN were composed of 1 wt.% monoterpene, 4 wt.% of Imwitor® 900K as a solid lipid and 2.5 wt.% of Poloxamer188 as a surfactant. Empty SLN consisted of 5 wt.% of Imwitor® 900K and 2.5 wt.% of Poloxamer188. The mean particles size (Z-Ave) and polydispersity index (PDI) of SLN were analyzed by dynamic light scattering (DLS), while the zeta potential (ZP) of each formulation were measured by electrophoretic light scattering. LUMiSizer® was applied to calculate the velocity distribution in the centrifugal field and instability index. Drug release profile from SLN was analyzed using Franz cell diffusion cells assayed by UV-Vis spectrophotometry, whereas the gas chromatography technique was applied to determine the encapsulation parameters of volatile monoterpenes. The matrix state, polymorphism and phase behavior of SLN were studied by X-ray diffraction (XRD, low and wide angles) and differential scanning calorimetry (DSC). Selected monoterpenes were successfully loaded in glycerol monostearate SLN. A burst release profile within the first 15 min was observed for all formulations, being the modified release profile dependent on the type of monoterpene and on the encapsulation efficiency.

Unravelling the molecular mechanisms of nickel in woodlice.

During the last few years, there has been an alarming increase in the amount of nickel (Ni) being released into the environment, primarily due to its use in the production of stainless steel but also from other sources such as batteries manufacturing and consequent disposal. The established biotic ligand models provide precise estimates for Ni bioavailability, in contrast, studies describing the mechanisms underpinning toxicological effect of Ni are scarce. This study exploits RNA-seq to determine the transcriptomic responses of isopods using Porcellionides pruinosus as an example of a terrestrial metal-resistant woodlouse. Furthermore, the recently proposed model for Ni adverse outcome pathways (Ni-AOP) presents an unprecedented opportunity to fit isopod responses to Ni toxicity and define Porcellionides pruinosus as a metalomic model. Prior to this study, P. pruinosus represented an important environmental sentinel, though lacking genetic/omic data. The reference transcriptome generated here thus represents a major advance and a novel resource. A detailed annotation of the transcripts obtained is presented together with the homology to genes/gene products from Metazoan and Arthropoda phylum, Gene Ontology (GO) classification, clusters of orthologous groups (COG) and assignment to KEGG metabolic pathways. The differential gene expression comparison was determined in response to nickel (Ni) exposure and used to derive the enriched pathways and processes. It revealed a significant impact on ion trafficking and storage, oxidative stress, neurotoxicity, reproduction impairment, genetics and epigenetics. Many of the processes observed support the current Ni-AOP although the data highlights that the current model can be improved by including epigenetic endpoints, which represents key chronic risks under a scenario of Ni toxicity.