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IntroductionCanine meningoencephalitis of unknown origin (MUO) is a debilitating disease associated with high mortality. The prognostic value of magnetic resonance imaging (MRI) findings for predicting survival at 12 months and long-term relapse remains uncertain.MethodsThis was a retrospective cohort study evaluating the prognostic value of different MRI variables using multivariable logistic regression and Cox proportional hazards analysis.ResultsIn total, 138 dogs were presumptively diagnosed with MUO. The most common location for lesions identified on MRI were the white matter tracts of the corona radiata and corpus callosum, followed by the frontal, sensorimotor and temporal cortices. Lower T2 lesion load (p = 0.006, OR = 0.942, CI = 0.902–0.983) was associated with longer survival and higher T1 post-contrast lesion load (p = 0.023, OR = 1.162, CI = 1.021–1.322) was associated with relapse.DiscussionThis study has identified prognostic factors that may help identify dogs at higher risk of death and relapse and therefore guide treatment recommendations.

Abstract Background Blood‐brain barrier (BBB) permeability can be assessed quantitatively using advanced imaging analysis. Hypothesis/Objectives Quantification and characterization of blood‐brain barrier dysfunction (BBBD) patterns in dogs with brain tumors can provide useful information about tumor biology and assist in distinguishing between gliomas and meningiomas. Animals Seventy‐eight hospitalized dogs with brain tumors and 12 control dogs without brain tumors. Methods In a 2‐arm study, images from a prospective dynamic contrast‐enhanced (DCE; n = 15) and a retrospective archived magnetic resonance imaging study (n = 63) were analyzed by DCE and subtraction enhancement analysis (SEA) to quantify BBB permeability in affected dogs relative to control dogs (n = 6 in each arm). For the SEA method, 2 ranges of postcontrast intensity differences, that is, high (HR) and low (LR), were evaluated as possible representations of 2 classes of BBB leakage. BBB score was calculated for each dog and was associated with clinical characteristics and tumor location and class. Permeability maps were generated, using the slope values (DCE) or intensity difference (SEA) of each voxel, and analyzed. Results Distinctive patterns and distributions of BBBD were identified for intra‐ and extra‐axial tumors. At a cutoff of 0.1, LR/HR BBB score ratio yielded a sensitivity of 80% and specificity of 100% in differentiating gliomas from meningiomas. Conclusions and Clinical Importance Blood‐brain barrier dysfunction quantification using advanced imaging analyses has the potential to be used for assessment of brain tumor characteristics and behavior and, particularly, to help differentiating gliomas from meningiomas.

Background: The closure of extensive burn wounds with widely expanded autologous split-thickness skin grafts (STSG) is associated with undesirable scar formation and contraction, due to the lack of dermis. Various materials for dermal replacement have been developed, either of xenogeneic, allogeneic or synthetic origin and are placed in the wound underneath a thin STSG in order to improve scar quality. In this study, a porcine wound model was used to compare several commercially available acellular dermal substitutes with an acellular dermal substitute prepared from glycerol preserved human skin: GlyadermⓇ. Methods: Antigenic components of the allografts were removed by incubation in the 0.06 M NaOH solution. In the first experiments, the dermal substitutes were applied to full thickness wounds and covered simultaneously with STSG. Controls were covered with STSG only. The wound healing response was analyzed for 8 weeks, both macroscopically and histologically. The Mann-Whitney U test was used for statistical analysis. In the second series of experiments, GlyadermⓇ was applied in a two-stage procedure in comparison to Integra. The STSG was placed on the dermal substitutes one week later. Results: In the first series, the inflammatory response and myofibroblast influx in GlyadermⓇ were limited, indicating possible beneficial outcomes on final wound healing results. The survival of the STSG on the acellular dermis was lower compared to the control wounds. Second series: the take of the STSG was the same as in the controls, but additionally wound contraction was reduced. The application of GlyadermⓇ was non-inferior to Integra. Conclusion: GlyadermⓇ can be successfully used for the reduction of wound contraction when applied in a two-stage procedure.

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In this article, I will address the use of the modal particle (MP) with the subjunctive in the main clauses in the Odyssey. I choose this feature, because this is a usage that is unknown to Attic and even in Ionic this is extremely rare. I first explain how the corpus was obtained, as the forms described as “future indicatives” in the grammars of Classical Greek descend either from the Indo-European desiderative and will be called “future-desideratives” here, or are metrically equivalent to the subjunctive of the sigmatic aorist, and as in the vast majority of cases, the distinction between desiderative and aorist subjunctive cannot be made, these forms are catalogued as “future-subjunctives”. In a second step, I discuss some of the textual issues that could arise in determining whether or not the MP was in fact attested. Thirdly, I outline a working hypothesis, outlining that the MP refers to single and specific action close to hearer and speaker and is only allowed with the epistemic modality (as in Allan’s 2013 framework). Fourthly, I provide the fact and figures and then, I start with the actual analysis. I find that there are no “future-desideratives” with an MP in the Odyssey and that only a very limited number of (future-)subjunctives are used with an MP in the main clause. This is due to the fact that most of these forms have a desiderative, voluntative and/or exhortative meaning, which are all three incompatible with the use of the MP. Besides the passages where the rules seem to be observed, I also discuss those in which the rules seem to have been violated, there are different variants attested or more than one interpretation possible.

Abstract Background Aging is one of the most important prognostic factors increasing the risk of clinical severity and mortality of COVID-19 infection. However, among patients over 75 years, little is known about post-acute functional decline. Objective The aim of this study was to identify factors associated with functional decline 3 months after COVID-19 onset, to identify long term COVID-19 symptoms and transitions between frailty statesafter COVID-19 onset in older hospitalized patients. Methods This prospective observational study included COVID-19 patients consecutively hospitalized from March to December 2020 in Acute Geriatric Ward in Nantes University Hospital. Functional decline, frailty status and long term symptoms were assessed at 3 month follow up. Functional status was assessed using the Activities of Daily Living simplified scale (ADL). Frailty status was evaluated using Clinical Frailty Scale (CFS). We performed multivariable analyses to identify factors associated with functional decline. Results Among the 318 patients hospitalized for COVID-19 infection, 198 were alive 3 months after discharge. At 3 months, functional decline occurred in 69 (36%) patients. In multivariable analysis, a significant association was found between functional decline and stroke (OR = 4,57, p = 0,003), history of depressive disorder (OR = 3,05, p = 0,016), complications (OR = 2,24, p = 0,039), length of stay (OR = 1,05, p = 0,025) and age (OR = 1,08, p = 0,028). At 3 months, 75 patients described long-term symptoms (49.0%). Of those with frailty (CFS scores ≥5) at 3-months follow-up, 30% were not frail at baseline. Increasing frailty defined by a worse CFS state between baseline and 3 months occurred in 41 patients (26.8%). Conclusions This study provides evidence that both the severity of the COVID-19 infection and preexisting medical conditions correlates with a functional decline at distance of the infection. This encourages practitioners to establish discharge personalized care plan based on a multidimensional geriatric assessment and in parallel on clinical severity evaluation.

OBJECTIVE: To assess the accuracy of "diabetes overtreatment" proxy definitions in predicting hypoglycemia in older adults with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: Inclusion of patients from HYPOAGE cohort with insulin-treated T2D, aged ≥75 years, and using a continuous glycemic monitoring (CGM) device for 28 days. "Diabetes overtreatment" was defined as HbA1c <7.0% (fixed proxy definition) or as HbA1c <7.0%, 7.5%, and 8.0% according to patient's health status (individualized proxy definition). The primary outcome was time below range (TBR) ≥1%. RESULTS: Of the 134 patients included (81.6 ± 5.4 years, 59% male), 25 (19%) and 53 (40%) were overtreated, based on fixed and individualized proxy definitions, respectively. CGM data showed TBR >1% in nearly all patients regardless of overtreatment status. Both proxy definitions had low sensitivity (20% [14; 29] and 41% [32; 50]) and accuracy (27% [20; 35] and 44% [35; 53]) in predicting hypoglycemia. CONCLUSIONS: A revised definition of diabetes overtreatment is needed to better manage older insulin-treated patients and protect them from hypoglycemia. [ABSTRACT FROM AUTHOR]

The social construction of rurality remains a collective fantasy of a safe, green, ethnically homogeneous environment. This fantasy, called “the rural idyll,” still dominates the way in which people give meaning to their lives, the lives of others, and the places where they live. This idyll is based on an interrelated urban/ethnic diverse versus rural/white dichotomy, even as rural areas are in fact becoming more ethnically diverse. The question of how ethnic diversity is understood, in traditional media, through the fantasy of the rural idyll is central to this paper. Drawing on recurring stories in 450 newspaper articles in the Flemish written press covering rural ethnic diversity, we identify four different ideal‐type frames: growing ethnic diversity as a (1) threat to the rural idyll, (2) confirmation of the rural idyll, (3) the consequence of rural deprivation, and (4) the solution to rural deprivation. Our analysis shows that a large proportion of the newspaper articles use “ethnic diversity as a threat to the rural idyll.” This connects with the long‐standing anti‐urban discourse in Flanders (Belgium). Nevertheless, the presence and emergence of other frames indicate that this discourse does not remain not unchallenged. [ABSTRACT FROM AUTHOR]

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Burn injuries can result in a significant inflammatory response, often leading to hypertrophic scarring (HTS). Local drug therapies e.g. corticoid injections are advised to treat HTS, although they are invasive, operator-dependent, extremely painful and do not permit extended drug release. Polymer-based microneedle (MN) arrays can offer a viable alternative to standard care, while allowing for direct, painless dermal drug delivery with tailorable drug release profile. In the current study, we synthesized photo-crosslinkable, acrylate-endcapped urethane-based poly(ε-caprolactone) (AUP-PCL) toward the fabrication of MNs. Physico-chemical characterization (1H-NMR, evaluation of swelling, gel fraction) of the developed polymer was performed and confirmed successful acrylation of PCL-diol. Subsequently, AUP-PCL, and commercially available PCL-based microneedle arrays were fabricated for comparative evaluation of the constructs. Hydrocortisone was chosen as model drug. To enhance the drug release efficiency of the MNs, Brij®35, a nonionic surfactant was exploited. The thermal properties of the MNs were evaluated via differential scanning calorimetry. Compression testing of the arrays confirmed that the MNs stay intact upon applying a load of 7 N, which correlates to the standard dermal insertion force of MNs. The drug release profile of the arrays was evaluated, suggesting that the developed PCL arrays can offer efficient drug delivery for up to two days, while the AUP-PCL arrays can provide a release up to three weeks. Finally, the insertion of MN arrays into skin samples was performed, followed by histological analysis demonstrating the AUP-PCL MNs outperforming the PCL arrays upon providing pyramidical-shaped perforations through the epidermal layer of the skin. HIGHLIGHTS: AUP-PCL MN arrays provide long-term transdermal drug delivery of hydrocortisone AUP-PCL-based MN arrays provide superior drug release profiles compared to PCL MNs Effective skin penetration AUP-PCL-based MNs on skin was achieved [ABSTRACT FROM AUTHOR]

Abstract Background Meningioma is the most common primary brain neoplasm in dogs. Further information is required regarding the expected long-term prognosis of dogs following the surgical resection of an intracranial meningioma together with the influence of adjunctive therapies. Whilst there have been several studies reporting the long-term outcome of intracranial meningioma resection following surgery alone, surgery with the use of an ultrasonic aspirator, surgery combined with radiotherapy and surgery combined with the addition of hydroxyurea, it is currently unclear which type of adjunctive therapy is associated with the most favourable outcomes. The objective of this study is to describe the presentation and outcome of dogs undergoing surgery for the resection of an intracranial meningioma and the effect of clinical factors, adjunctive therapies and meningioma histopathological subtype on the long-term outcome. Results A hundred and one dogs that had intracranial surgery for meningioma resection were investigated from four referral centres. 94% of dogs survived to hospital discharge with a median survival time of 386 days. Approximately 50% of dogs survived for less than a year, 25% survived between 1 and 2 years, 15% survived between 2 and 3 years and 10% survived for greater than 3 years following discharge from hospital. One or more adjunctive therapies were used in 75 dogs and the analysis of the data did not reveal a clear benefit of a specific type of adjunctive therapy. Those dogs that had a transfrontal approach had a significantly reduced survival time (MST 184 days) compared to those dogs that had a rostrotentorial approach (MST 646 days; p

Background and ObjectivesThe Western Cape public pediatric cardiac service is under-resourced. COVID-19 regulations are likely to have long-term effects on patient care but may provide insight into service capacity requirements. As such, we aimed to quantify the impact of COVID-19 regulations on this service.MethodsAn uncontrolled retrospective pre-post study of all presenting patients over two, one-year periods; the pre-COVID-19 period (01/03/2019–29/02/2020) and the peri-COVID-19 period (01/03/2020–28/02/2021).ResultsAdmissions decreased by 39% (624 to 378) and cardiac surgeries decreased by 29% (293 to 208) in the peri-COVID-19 period, with an increase in urgent cases (PR:5.99, 95%CI:3.58–10.02, p

Abstract Introduction Sepsis and septic shock cause significant mortality worldwide, with no targeted molecular therapies available. Metformin has pleomorphic effects that may be beneficial in sepsis, but at present, the impact of metformin exposure on sepsis remains controversial. Metformin might alter lactate metabolism, but little is known about its influence on lactate kinetics. We therefore investigated the impact of preadmission metformin use on lactate kinetics, acute kidney injury (AKI) and mortality in sepsis. Materials and Methods We retrospectively analysed all ICU admissions with sepsis and septic shock between January 2013 and September 2020, identifying 77 users and 390 nonusers (subdivided in diabetics, n = 48 and nondiabetics, n = 342). Results (Sub)groups did not differ in illness severity or sepsis aetiology. Admission lactate levels were similar, but evolution in lactate over the first 24 h showed a larger decrease in users vs nonusers (median − 53% vs. −36%, p = .010). No difference in AKI or renal replacement therapy was found. Mortality was lower in users vs nonusers in case of septic shock (21.9% (n = 7) vs. 42.7% (n = 61) for 90d mortality, p = .029, OR 0.38 [95% CI: 0.15–0.93]), but showed no significant differences in the combined sepsis and septic shock population. Conclusions In our data, preadmission metformin use is associated with a significantly larger decrease in lactate after admission with sepsis or septic shock and with reduced mortality in septic shock. This underscores the need for further studies investigating the interplay between metformin, lactate and sepsis, thereby exploring the potential use of metformin or its pathways in sepsis.

IntroductionAutologous split thickness skin grafting is the standard-of-care for most deep dermal and full thickness skin defects. Historically, mesh grafting is used to expand skin grafts for smaller defects and other techniques such as Meek micrografting is used to enable expansion for larger skin defects. Yet, Meek micrografting is increasingly used for smaller skin defects as well. Both techniques are frequently used, especially in burn centers, but evidence on which one is preferable for relative smaller skin defects is lacking. Therefore, an intra-patient randomized controlled trial was designed to adequately compare multiple outcomes of the Meek micrografting and mesh grafting techniques.Materials and methodsA multicenter intra-patient controlled randomized trial is being performed in two burn centers (the Netherlands and Belgium) to compare multiple outcomes of Meek micrografting and mesh grafting burns or skin defects. Study registration number (NL74274.029.20). Adult patients with a (burn) wound and an indication for surgical excision and skin grafting were screened for inclusion. In total 70 patients will be included and the primary outcome is scar quality twelve months post-surgery assessed by the Patient and Observer Scar Assessment Scale. Moreover, graft take, re-epithelialization, infection rate, donor site size and patients' preference are also measured within hospital admission, on 3 months and 12 months post-surgery.DiscussionThis is the first randomized trial that is intra-patient controlled, which enables a proper comparison between both skin expansion techniques. The results of this study will contribute to the clarification of the indications of both techniques and ample attention is paid for the patients' opinion on the surgical treatment options.