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Background and Purpose Experimental Approach Key Results Conclusion and Implications Recent research linking choline‐containing lipids to degeneration of basal forebrain cholinergic neurons in neuropathological states illustrates the challenge of balancing lipid integrity with optimal acetylcholine levels, essential for memory preservation. The endocannabinoid system influences learning and memory processes regulated by cholinergic neurotransmission. Therefore, we hypothesised that activation of the endocannabinoid system may confer neuroprotection against cholinergic degeneration.We examined the neuroprotective potential of sub‐chronic treatments with the cannabinoid agonist WIN55,212‐2, using ex vivo organotypic tissue cultures including nucleus basalis magnocellularis and cortex and in vivo rat models of specific cholinergic damage induced by 192IgG‐saporin. Levels of lipids, choline and acetylcholine were measured with histochemical and immunofluorescence assays, along with [35S]GTPγS autoradiography of cannabinoid and muscarinic GPCRs and MALDI‐mass spectrometry imaging analysis. Learning and memory were assessed by the Barnes maze and the novel object recognition test in rats and in the 3xTg‐AD mouse model.Degeneration, induced by 192IgG‐saporin, of baso‐cortical cholinergic pathways resulted in memory deficits and decreased cortical levels of lysophosphatidylcholines (LPC). WIN55,212‐2 restored cortical cholinergic transmission and LPC levels via activation of cannabinoid receptors. This activation altered cortical lipid homeostasis mainly by reducing sphingomyelins in lesioned animals. These modifications were crucial for memory recovery.We hypothesise that WIN55,212‐2 facilitates an alternative choline source by breaking down sphingomyelins, leading to elevated cortical acetylcholine levels and LPCs. These results imply that altering choline‐containing lipids via activation of cannabinoid receptors presents a promising therapeutic approach for dementia linked to cholinergic dysfunction. [ABSTRACT FROM AUTHOR]

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Background: Soluble P‐selectin (sP‐selectin) has been proposed as a potential biomarker for venous thromboembolism (VTE) diagnosis with interesting results. However, its role in predicting early mortality in pulmonary embolism (PE) remains unexplored. Methods: This observational, prospective, single‐center study enrolled consecutive patients aged 18 or older with confirmed acute symptomatic PE and no prior anticoagulation. The study aims to assess the prognostic capacity of sP‐selectin measured at the time of PE diagnosis for short‐term mortality and major bleeding. Results: A total of 196 patients, with a mean age of 69.1 years (SD 17), were included, of whom 52.6% were male. Within 30 days, 9.7% of patients (n = 19) died, and 5.1% (n = 10) suffered major bleeding. PE risk stratification revealed 4.6% (n = 9) with high‐risk PE, 34.7% (n = 68) with intermediate‐high‐risk PE, 38.3% (n = 75) with intermediate‐low‐risk PE, and 22.5% (n = 44) with low‐risk PE according to the European Society of Cardiology score. Mean plasma sP‐selectin levels were comparable between survivors and non‐survivors (489.7 ng/mL ±63 vs. 497.3 ng/mL ±51; p =.9). The ROC curve for 30‐day all‐cause mortality and major bleeding yielded an AUC of 0.49 (95% CI 0.36–0.63) and 0.46 (95% CI 0.24–0.68), respectively. Multivariate and survival analyses were precluded due to lack of significance. Conclusions: sP‐selectin was not useful for predicting short‐term mortality or major bleeding in patients with acute symptomatic pulmonary embolism. Further studies are required to clarify the role of sP‐selectin in VTE, particularly in prognosticating PE outcomes. [ABSTRACT FROM AUTHOR]

Background: Short‐term cognitive impairment is associated with SARS‐CoV‐2 infection but the long‐term impact is yet to be examined in detail. We aim to study the evolution of these symptoms in severe COVID‐19 patients admitted to the intensive care unit (ICU) between April and December 2020 1 year after hospital discharge and to analyze its clinical correlates. Method: A total of 58 patients agreed to participate in the 6 months follow‐up and 30 at 1 year after hospital discharge. Demographic, clinical and laboratory data were collected and a comprehensive neuropsychological battery including validated tests for the main cognitive domains was administered. To test the magnitude of neurocognitive sequelae, two standard deviations below normative group were considered. To compare the neuropsychological performance at 6 and 12 months follow‐up we used repeated measures tests. Finally, regression analyses were performed to test the main effects of medical and psychological factors on multiple cognition. Results: Almost half of the sample continued to have impaired performance on neuropsychological tests at 12 months follow‐up. In comparison with the results obtained at 6 months, significant improvements were found in immediate recall (d = 0.49), delayed recall (d = 0.45), and inhibitory control (d = 0.53). Medical variables predicted cognitive performance at 6 months but not at 12 months follow‐up, while anxiety and depression predicted cognitive deficits in the long‐term. Conclusions: A generalised improvement was observed in severe COVID‐19 patients at follow‐up. This improvement was particularly notable in verbal memory and executive functioning. However, a considerable proportion of the sample continued to present deficits at 1 year follow‐up. [ABSTRACT FROM AUTHOR]

A 14‐month‐old girl with very early‐onset inflammatory bowel disease (VEO‐IBD) was admitted with a flare of her bowel disease and subsequently developed high fevers, joint pain, and skin lesions during her hospitalization. Workup demonstrated bowel‐associated dermatosis‐arthritis syndrome in the setting of VEO‐IBD, a neutrophilic dermatosis rarely reported in children that can be challenging to diagnose and treat, with limited literature for patients under 2 years of age. [ABSTRACT FROM AUTHOR]

The article discusses a case of alopecic and eroded scalp plaque in a newborn female, diagnosed as erosive pustular dermatosis of the scalp (EPDS). EPDS is an inflammatory disease typically seen in elderly individuals but can also occur in pediatric cases. The condition may manifest after trauma, surgery, or other skin injuries, leading to scarring alopecia. Treatment with topical corticosteroids was effective in this case, emphasizing the importance of early recognition and intervention in such cases. [Extracted from the article]

Lanthanides have unique photoluminescence (PL) emission properties, including very long PL lifetimes. This makes them ideal for biological imaging applications, especially using PL lifetime imaging microscopy (PLIM). PLIM is an inherently multidimensional technique with exceptional advantages for quantitative biological imaging. Unfortunately, due to the required prolonged acquisitions times, photobleaching of lanthanide PL emission currently constitutes one of the main drawbacks of PLIM. In this study, we report a small aqueous‐soluble, lanthanide antenna, 8‐methoxy‐2‐oxo‐1,2,4,5‐tetrahydrocyclopenta[de]quinoline‐3‐phosphonic acid, PAnt, specifically designed to dynamically interact with lanthanide ions, serving as exchangeable dye aimed at mitigating photobleaching in PLIM microscopy in cellulo. Thus, self‐assembled lanthanide complexes that may be photobleached during image acquisition are continuously replenished by intact lanthanide antennas from a large reservoir. Remarkably, our self‐assembled lanthanide complex clearly demonstrated a significant reduction of PL photobleaching when compared to well‐established lanthanide cryptates, used for bioimaging. This concept of exchangeable lanthanide antennas opens new possibilities for quantitative PLIM bioimaging. [ABSTRACT FROM AUTHOR]

Objective: To review and synthesize existing evidence on the effectiveness of mirror therapy (MT) compared to active exercise‐based interventions (ie, cross‐training and conventional exercise) for reducing spasticity and sensory impairment in stroke survivors. Type: Systematic Review and Metanalysis. Literature Survey: Pubmed/MEDLINE, Cochrane, Embase, CINAHL, and Physiotherapy Evidence Database (PEDro), were searched. Methodology: Randomized controlled trials (RCTs) that investigated MT effectiveness in improving spasticity and sensory impairment in stroke survivors compared to a control group. Synthesis: Fifteen RCTs (653 volunteers) were included. Spasticity improvements achieved with MT were similar to those obtained with cross‐training (standard mean difference [SMD]: 0.12, 95% confidence interval [CI]: −0.43 to 0.68). In addition, when further combined with conventional exercise, spasticity improved similarly in both groups (SMD: 0.10, 95% CI: −0.16, 0.36). Lastly, when MT plus exercise was compared to exercise alone, spasticity decreased in both groups (SMD: 0.16, 95% CI: −0.16 to 0.48). Nevertheless, none of the Interventions seem effective on sensory impairment (SMD: 0.27, 95% CI: −0.28 to 0.81). Conclusions: MT is equally effective as other exercise therapies, such as cross‐training and conventional exercise, for improving spasticity in stroke survivors, whereas none of the explored interventions yielded beneficial effects on sensory impairment. Further well‐designed RCTs are needed to confirm the results. [ABSTRACT FROM AUTHOR]

Objectives: So far, no 87Sr/86Sr mobility studies have been done for Neolithic remains from Belgium and information on the Sr isotopic variability in the region is scarce. This study aims to explore mobility in a Final Neolithic population from the funerary cave 'Grotte de La Faucille', contribute to the understanding of the isotopic composition of bioavailable Sr in Belgium, assess evidence for male mobility using proteomic analysis, and explore possible places of origin for nonlocal individuals. Materials and Methods: The 87Sr/86Sr isotope ratio of dental enamel from six adults and six juveniles was determined. Liquid chromatography mass spectrometry‐based protein analysis was employed to identify individuals of male biological sex. 87Sr/86Sr of micromammal teeth, snail shells, and modern plants from three geological areas in Belgium were measured to establish isotopic signatures for bioavailable strontium. Nonlocality was assessed by comparing human 87Sr/86Sr isotope ratios to the 87Sr/86Sr range for bioavailable Sr. Results: Four individuals yielded 87Sr/86Sr isotope ratios consistent with a nonlocal origin. No statistical differences were found between adults and juveniles. Three males were detected in the sample set, of which two show nonlocal 87Sr/86Sr values. Discussion: This study provides evidence for mobility in Final Neolithic Belgium. The four nonlocal 87Sr/86Sr signatures correspond with the 87Sr/86Sr of bio‐available Sr in Dutch South Limburg, the Black Forest in Southwest Germany, and regions of France, such as parts of the Paris Basin and the Vosges. The results support the ruling hypothesis of connections with Northern France, brought to light by archeological research. [ABSTRACT FROM AUTHOR]

Background: Haemophilic arthropathy is one of the main causes of morbidity in people with haemophilia (PWH), inducing pain and reduced functionality. Therefore, PWH are complex patients and must be approached from a multidisciplinary perspective. Objectives: To evaluate the effectiveness of a therapeutic exercise and cognitive‐behavioural therapy (CBT) combined protocol on functionality, pain, and joint health of PWH, arthropathy and chronic pain. Treatment satisfaction was also evaluated. Methods: A single‐blinded clinical trial with 21 PWH in prophylactic regimen was carried out. Participants were divided into an experimental group (EG, n = 11) and a control group (CG, n = 10). The EG underwent a 4‐month programme of home‐based therapeutic exercise plus CBT, whilst CG performed their daily activities. Patients were evaluated at baseline, post‐intervention and after 12 additional weeks. Measures of functionality (Haemophilia Activities List, Timed Up and Go Test, 2‐Minutes‐Walking‐Test and Sit‐to‐Stand Test), pain (PainDETECT and Visual Analogue Scale) and joint health (Haemophilia Joint Health Score) were taken. Related dimensions of the A36 Haemophilia Quality of Life Questionnaire were calculated. Effects were calculated using a two‐factor ANOVA. Results: The EG showed significant improvements in function (p <.001), pain (p <.001), joint damage (p =.006), and satisfaction with the treatment (p =.006) dimensions of the A36 Haemophilia Quality of Life Questionnaire, as well as in pain measured with the Visual Analogue Scale (p =.008) and PainDETECT (p =.035). Conclusions: The combined physiotherapy and CBT protocol showed a partial improvement in functionality, pain and joint health of PWH, arthropathy and chronic pain. In addition, participants were satisfied with the treatment. [ABSTRACT FROM AUTHOR]

Keratitis‐ichthyosis‐deafness (KID) syndrome is a rare genetic disease caused by pathogenic variants in connexin 26 (gene GJB2), which is part of the transmembrane channels of the epithelia. Connexin 26 is expressed mainly in the cornea, the sensory epithelium of the inner ear, and in the skin keratinocytes, which are the three main target organs in KID syndrome. Approximately a dozen pathogenic variants have been described to date, including some lethal forms. Patients with lethal pathogenic variants present with severe symptoms from birth and die from sepsis during the first year of life. We present a premature female patient with KID syndrome carrying the lethal p.Ala88Val pathogenic variant in GJB2. In addition to the respiratory distress associated with this variant, our patient presented severe hypercalcemia of unexplained origin refractory to treatment. This abnormality has not been reported earlier in other patients with KID syndrome with the same variant. [ABSTRACT FROM AUTHOR]

Nursing staff plays a key role in the public health response to the COVID‐19 pandemic, being in the front line of care. This study sought to synthesise the qualitative literature on care experiences of frontline nurses during the COVID‐19 pandemic. A search was conducted on five databases in January 2021. Fifteen qualitative studies met the inclusion criteria and were included in the research, being submitted to interpretive meta‐synthesis according to the eMERGe guide. The final synthesis included a line of argument that shows the experiences of frontline nurses during the COVID‐19 pandemic, divided into three major themes: 'Instability on the edge of a cliff: unpredictable and unknown context,' 'The price of walking the tightrope: the uncertainty surrounding care,' and 'Finding the balance to reach the other side: dealing with the emotional demands of care.' Although essential in the health response to the COVID‐19 pandemic, nurses experienced an emotional impact arising from the hampered care provision. Our results point to need for strengthening the training of nurses and future nurses, creating and promoting measures that contribute to their psycho‐emotional well‐being, ensuring a safe environment for their clinical practice, and promoting their participation in decision‐making processes. [ABSTRACT FROM AUTHOR]

Background: Guidelines and expert recommendations on infantile hemangiomas (IH) are aimed at increasing homogeneity in clinical decisions based on the risk of sequelae. Objective: The objective was to analyze the inter‐ and intra‐observer agreement among pediatric dermatologists in the choice of treatment for IH. Methods: We performed a cross‐sectional inter‐rater and intra‐rater agreement study within the Spanish infantile hemangioma registry. Twenty‐seven pediatric dermatologists were invited to participate in a survey with 50 clinical vignettes randomly selected within the registry. Each vignette contained a picture of an infantile hemangioma with a clinical description. Raters chose therapy among observation, topical timolol, or oral propranolol. The same survey reordered was completed 1 month later to assess intra‐rater agreement. Vignettes were stratified into hemangioma risk categories following the Spanish consensus on IH. The agreement was measured using kappa statistics appropriate for the type of data (Gwet's AC1 coefficient and Gwet's paired t test). Results: Twenty‐four dermatologists completed the survey. Vignettes represented 7.8% of the Spanish hemangioma registry. The inter‐rater agreement on the treatment decision was fair (AC1 = 0.39, 95% confidence interval [CI]: 0.30–0.47). When stratified by risk category, good agreement was reached for high‐risk hemangiomas (AC1 = 0.77, 95% CI: 0.51–1.00), whereas for intermediate‐ and low‐risk categories, the agreement was only fair (AC1 0.31, 95% CI: 0.16–0.46 and AC1 = 0.38, 95% CI: 0.27–0.48, respectively). Propranolol was the main option for high‐risk hemangiomas (86.4%), timolol for intermediate‐risk (36.8%), and observation for low‐risk ones (55.9%). The intra‐rater agreement was good. The inter‐rater agreement between pediatric dermatologists on the treatment of IH is only fair. Variability was most significant with intermediate‐ and low‐risk hemangiomas. [ABSTRACT FROM AUTHOR]

Introduction: Balance training is important to improve balance and to decrease the risk of falls in patients with haemophilia (PWH). Aim: To analyse the current knowledge about the effectiveness of physical exercise on postural balance in PWH. Methods: A systematic search for clinical trials, published before November 2021, was conducted using the following electronic databases: PubMed/MEDLINE, Web of Science, Embase, Wiley Online Library and the Cochrane Central Register of Controlled Trials (CENTRAL). Two independent reviewers extracted the data and assessed the risk of bias. The certainty of the evidence was analyzed using GRADE. Results: A total of ten studies involving 304 patients were included. The studies performed strength and balance exercises, and some included flexibility, mobilization, and/or aerobic exercises in their training programs. Postural balance was evaluated using a force platform and the one leg stand test was the most frequently used. Only five exercise programs achieved a significant increase in balance (pre‐post) with a strength, postural balance, flexibility, and aerobic intervention. In general, the quality rate of the risk of bias was fair but the overall quality of the evidence across the studies was very low. Conclusion: Five studies showed that there is a positive change in balance after the intervention. However, there is currently an unclear demonstration of evidence for the use of physical exercises to improve postural balance in people with haemophilia. Further studies with a higher methodological quality are needed. [ABSTRACT FROM AUTHOR]

Storage of aversive memories is of utmost importance for survival, allowing animals to avoid upcoming similar stimuli. However, without reinforcement, the learned avoidance response gradually decreases over time. Although the molecular mechanisms controlling this extinction process are not well known, there is evidence that the endocannabinoid system plays a key role through CB1 receptor‐mediated modulation of cholinergic signaling. In this study, we measured fear extinction throughout 7 months using naïve rats, assessed in passive avoidance (PA) test in a non‐reinforced manner. Then, we evaluated the effect of gentle handling and non‐aversive novel object recognition test (NORT) on the extinction and expression of fear memories by measuring passive avoidance responses. Neurochemical correlates were analyzed by functional autoradiography for cannabinoid, cholinergic, and dopaminergic receptors. Despite results showing a gradual decrease of passive avoidance response, it did not fully disappear even after 7 months, indicating the robustness of this process. Meanwhile, in rats that received gentle handling or performed NORT after receiving the PA aversive stimulus, extinction occurred within a week. In contrast, gentle handling performed before receiving the aversive stimulus exacerbated fear expression and triggered escape response in PA. The neurochemical analysis showed increased cannabinoid and cholinergic activity in the nucleus basalis magnocellularis (NBM) in rats that had performed only PA, as opposed to rats that received gentle handling before PA. Additionally, a correlation between CB1 mediated‐signaling in the NBM and freezing in PA was found, suggesting that the endocannabinoid system might be responsible for modulating fear response induced by aversive memories. [ABSTRACT FROM AUTHOR]

We have optimized a synthetic approach to (±)‐Ferrugine in 8 steps starting from 5‐aminocyclohept‐1‐ene and using the Brønsted acid‐catalyzed pseudotransannular ring‐opening of the epoxide derived from this cycloheptene as the key step for the construction of the 8‐azabicyclo[3.2.1]octane central core. While attempting the enantioselective synthesis of this natural product from enantiopure 2‐hydroxy‐8‐azabicyclo[3.2.1]octane we have found that this compound shows a pronounced tendency to racemize via an achiral symmetric aziridinium intermediate. This racemization side process has been studied in detail using both experimental and computational methods. [ABSTRACT FROM AUTHOR]

Introduction: More than half of adult patients with severe haemophilia (PWH) suffer pain daily, with chronic pain (CP) in more than 15% of cases, thereby reducing their quality of life (QoL). However, there are no evidence‐based therapeutic guidelines for pain management. Aim: To evaluate the effectiveness of a combined protocol based on psychology and physiotherapy in the improvement of CP self‐efficacy in PWH with CP. Secondary outcomes are changes in QoL, emotional status, pain and kinesiophobia. Methods: In this prospective controlled trial study, recruited patients were allocated either to an experimental group (EG, n = 10) or to a control group (CG, n = 9). EG received interventions over four months: one cognitive‐behavioural therapy (CBT) session per month and three home exercise sessions per week. Self‐efficacy (Chronic Pain Self‐Efficacy Scale), QoL (A36 Hemophilia‐QoL), emotional status (Hospital Anxiety and Depression Scale and Rosenberg's Self‐esteem Scale), pain (Visual Analogue Scale) and kinesiophobia (Tampa Scale for Kinesiophobia) were assessed at three time points (Week 0, Month 4 and Month 7). The intervention effects were determined with mixed 2‐factor ANOVAs. Results: The EG showed a significant improvement (p <.05) in the control of symptoms and pain management scores on the Self‐Efficacy Scale, QoL, self‐esteem emotional status, pain and kinesiophobia. The intervention effects remained significant (p <.05) over time for pain management, QoL, pain and kinesiophobia. Conclusion: The non‐pharmacological treatment applied based on CBT and physiotherapy showed to be effective in improving CP self‐efficacy, QoL and emotional status, while reducing pain and kinesiophobia in PWH with CP. [ABSTRACT FROM AUTHOR]

A technique for the reduction of third‐order intermodulation distortion (IMD3) occurring in bulk acoustic wave (BAW) filters and multiplexers is presented. The method consists of using the intrinsic second‐order intermodulation distortion generated by BAW filters and multiplexers themselves by injecting an externally controlled amplitude and phase modulated signal at low frequency to compensate for the IMD3. The proposed technique has been experimentally verified by performing IMD3 measurements in a single BAW resonator subject to several modulated signals under a nonlinear scenario. [ABSTRACT FROM AUTHOR]

All elements with two or more isotopes show natural variation in their isotopic composition as a result of the isotope fractionation that accompanies (bio)chemical reactions and (bio)physical processes. Multicollector inductively coupled plasma‐mass spectrometry (MC‐ICP‐MS) offers the precision required to reveal and quantify the differences in isotope ratios thus caused, although they are often of sub‐permil magnitude only. Using MC‐ICP‐MS, it has been shown that (a) in different body compartments, essential mineral elements may display different isotopic compositions, and (b) disease conditions may alter the isotopic composition of an essential mineral element in a biofluid and/or tissue. As a result, high‐precision isotopic analysis of these elements is a powerful way to unravel the actual role these essential mineral elements play in specific biochemical processes. Moreover, isotope ratio shifts also show promise as a diagnostic or prognostic tool. Despite the intensive sample pretreatment preceding MC‐ICP‐MS isotopic analysis and the high purchase and running costs of the instrumentation, this approach may be valuable, especially for diseases that can otherwise only be established at a later stage and/or via a more invasive approach. This review paper describes the basics of "biomedical isotopic analysis" and uses selected cases from the literature to sketch the state‐of‐art and illustrate in which context isotope ratio markers could be exploited in a clinical context. [ABSTRACT FROM AUTHOR]

Dyskeratosis congenita (DC) is an unusual inherited disease characterized by the triad of mucosal leukoplakia, nail dystrophy, and skin pigmentation. Hyperkeratosis of the palms and soles is another reported skin finding. This hyperkeratosis can lead to fissures, chronic erosion, and deep ulcerations. These atypical wounds are not only a diagnostic but a therapeutic challenge for clinicians, and there are no standardized treatments for these types of chronic wounds. Punch grafting is a traditional and minimally invasive technique to enhance wound healing, and it has been associated with significant and quick pain reduction in ulcers with various underlying causes. Herein, we describe a patient with DC with a chronic and refractory plantar ulcer successfully treated with punch grafting. [ABSTRACT FROM AUTHOR]

High‐frequency ultrasonography (HFUS) represents a useful adjunct for dermatologists in the diagnosis of capillary malformation‐arteriovenous malformation (CM‐AVM) syndrome. We present a paediatric case series of 6 patients with confirmed RASA1 gene mutation in whom HFUS demonstrated AVM beneath cutaneous CM‐like lesions greater than 1.5 cm. [ABSTRACT FROM AUTHOR]

Supported cinchone‐derived thioureas promote highly enantioselective aza‐Friedel‐Crafts reaction of different naphthols with a variety of N‐Boc ketimines derived from isatin. The catalysts are recoverable and reusable, and one of the supported catalysts has been used in a flow process allowing the synthesis of 3‐amino‐2‐oxindole derivatives in multigram scale with high yield and enantioselectivity. [ABSTRACT FROM AUTHOR]

Background: The capacity of profilin to induce allergic symptoms in patients with respiratory allergy has been questioned. In this sense, the aim of this study was to investigate the correlation between profilin exposure and induction of symptoms in a prospective case‐control study. Methods: The concentration of profilin as well as pollen levels in the air was measured. A diary score of symptoms was collected from allergic patients. Seventy‐nine individuals were included in the study; fifty cases and 28 controls were positive or negative to profilin, respectively. Conjunctival and bronchial provocation tests were performed with purified profilin (Pho d 2) in a subgroup of cases and controls. Results: Profilin was detected in the environment on 133 days (maximum peak of 0.56 ng/m3). A positive correlation between profilin and pollen count of Olea and Poaceae was observed (ρ = 0.24; P <.001). Intensity of total, nasal and ocular symptoms was statistically higher in cases than in controls (P <.001). The risk of suffering symptoms, measured by the percentage of patients who presented any of the symptoms each day, was also higher in cases than in controls. The provocation test was positive in 95% of bronchial and 90% of conjunctival challenges in cases, and negative in all controls. Conclusions: Profilin was detected in the environment and had the ability to induce a specific allergen response. Patients sensitized to this panallergen showed more symptoms and were more likely to have symptoms. Therefore, sensitization to profilin seems to be a marker of severity in patients with rhinoconjunctivitis and asthma mediated by pollen. [ABSTRACT FROM AUTHOR]

Within the educational system, heritage‐related curriculum design and contents constitute a key factor in the sustainable preservation of heritage since only what is known and valued can be protected and preserved. Whether heritage education involves the inclusion of new materials in the curriculum, or the use of innovative approaches in handling heritage‐related contents that are already present in the several curricular areas in order to facilitate their teaching and promote heritage awareness, the fact remains that the curriculum itself becomes an important player. Our research aims at analysing the way heritage is approached in the 17 Decrees regulating the Primary Education curriculum in the Spanish territory. The results show that the methodological criterion used in the teaching‐learning of heritage is the sensitisation sequence: Knowing, Understanding, Respecting, Valuing, Sensitising, Taking Care, Transmitting, Heritagising and Identising. On the other hand, there are major differences across Spain's regions regarding heritage awareness and curricular coverage: an issue that should be borne in mind in curriculum revision processes and in the design of academic programmes targeted at future teachers in order to secure the quality of heritage education. [ABSTRACT FROM AUTHOR]

High‐frequency ultrasonography represents a promising tool for pediatric dermatologists. It is a non‐invasive diagnostic technique that is particularly appealing when working with children. It can be easily performed at the patient's bedside, avoiding diagnostic delays, sedation, or multiple visits. It represents a useful adjunct to clinical examination and can enhance our understanding of cutaneous diseases. Patient cooperation and limited training and experience are the main challenges for cutaneous ultrasonography in pediatric dermatology. This review describes cutaneous ultrasonography and the nuances of its use in the pediatric setting, followed by the ultrasonographic findings of cutaneous lumps, bumps, and inflammatory dermatoses commonly encountered in pediatric patients. [ABSTRACT FROM AUTHOR]

High‐frequency ultrasonography represents a promising tool for pediatric dermatologists. It is a noninvasive and harmless diagnostic technique that is especially appealing when working with children. It can be easily performed at the patient's bedside, avoiding diagnostic delays, sedation, or multiple visits. It represents a useful adjunct to clinical examination and aids our understanding of cutaneous pathology. In this second part, we describe the ultrasonographic findings of developmental anomalies and vascular lesions. [ABSTRACT FROM AUTHOR]

The article discusses a significant advancement in quantitative PLIM bioimaging called PAnt (phosphonic acid antenna). PAnt is a small water-soluble lanthanide antenna that can self-assemble with lanthanide ions, serving as an exchangeable probe to overcome photobleaching in PLIM microscopy in cellulo. This allows for continuous replenishment of lanthanide complexes that may be photobleached during acquisition, resulting in remarkable photostability compared to traditional lanthanide cryptates. The research was conducted by Angel Orte, Juan A. González-Vera, and their team, and the article includes artwork by M. Eugenio Vázquez from the University of Santiago de Compostela. [Extracted from the article]

The article discusses a significant advancement in quantitative PLIM bioimaging called PAnt (phosphonic acid antenna). PAnt is a small water-soluble lanthanide antenna that can self-assemble with lanthanide ions, serving as an exchangeable probe to overcome photobleaching in PLIM microscopy in cellulo. The use of PAnt allows for continuous replenishment of lanthanide complexes that may be photobleached during acquisition, resulting in remarkable photostability compared to traditional lanthanide cryptates. The research was conducted by Angel Orte, Juan A. González-Vera, and their colleagues. [Extracted from the article]

We report the case of a 12-month-old infant who presented with progressive lower limb enlargement associated with erythema mimicking an arteriovenous malformation. Computed tomography confirmed an arteriovenous fistula (AVF) between the deep femoral artery and the common femoral vein. This case describes the unique clinical and imaging findings of iatrogenic AVF and contrasts them with other congenital vascular entities. [ABSTRACT FROM AUTHOR]

Her past medical history was remarkable for the recent onset of systemic lupus erythematosus (SLE). (b) Subepidermal blister with no inflammatory infiltrate (H&E staining, 10×). gl Childhood-onset SLE is a chronic inflammatory disease that affects the kidneys in about 50% of patients. A 12-year-old girl was referred to our department for asymptomatic blisters in her arms, trunk and legs that had appeared 1 week earlier. [Extracted from the article]

PURPOSE: To determine nursing diagnoses in people with a digestive stoma and their relationship with sociodemographic and clinical variables. METHOD: A cross-sectional descriptive study of 102 subjects in the General Surgery Unit of a first-level hospital (Granada, Spain) was conducted. Data were collected on the presence of nursing diagnoses, sociodemographic and clinical variables. RESULTS: NANDA-I: “Deficient knowledge (00126)” and “Readiness for enhanced health management (00162)” were present in the entire sample studied. The period of care (postoperative vs. follow-up) was the most common significant variable among diagnoses. CONCLUSIONS: This work contributes to the determination of NANDA-I diagnoses in people with digestive stomas. IMPLICATIONS FOR NURSING PRACTICE: The results provide a guide to help nursing professionals develop individual care plans. [ABSTRACT FROM AUTHOR]

The Bruton's tyrosine kinase (BTK) inhibitor ibrutinib has been shown to be highly effective in patients with chronic lymphocytic leukemia (CLL) and is approved for CLL treatment. Unfortunately, resistance and intolerance to ibrutinib has been observed in several studies, opening the door for more specific BTK inhibitors. CC‐292 (spebrutinib) is a BTK inhibitor with increased specificity for BTK and less inhibition of other kinases. Our in vitro studies showed that CC‐292 potently inhibited B‐cell receptor signaling, activation, proliferation and chemotaxis of CLL cells. In in vivo studies using the adoptive transfer TCL1 mouse model of CLL, CC‐292 reduced tumor load and normalized tumor‐associated expansion of T cells and monocytes, while not affecting T cell function. Importantly, the combination of CC‐292 and bendamustine impaired CLL cell proliferation in vivo and enhanced the control of CLL progression. Our results demonstrate that CC‐292 is a specific BTK inhibitor with promising performance in combination with bendamustine in CLL. Further clinical trials are warranted to investigate the therapeutic efficacy of this combination regimen. What's new? B‐cell receptor (BCR) signaling plays a pivotal role in chronic lymphocytic leukemia (CLL). BTK inhibitor ibrutinib has been shown to be highly effective in patients, but resistance and intolerance have also been observed. Here, the authors demonstrate that the more specific CC‐292 disrupts BCR signaling and inhibits tumor cell activation, proliferation, and chemotaxis in vitro. In mice, CC‐292 reduces tumor load and normalizes tumor‐associated expansion of T cells and monocytes while not affecting T cell function. Combination of CC‐292 and bendamustine impairs CLL cell proliferation and normalizes immune cell composition, which overcomes microenvironment‐mediated chemoresistance and enhances control of CLL progression. [ABSTRACT FROM AUTHOR]

Introduction: The joint range of motion (ROM) is an important clinical parameter used to assess the loss of functionality resulting from joint bleedings in people with haemophilia. These episodes require a close follow‐up and, to decrease patients' hospital dependence, telemedicine tools are needed. Therefore, this study is aimed to analyse the validity of the Microsoft Kinect V2 sensor with corrected angle measurement to be used in the monitoring of elbow ROM in people with haemophilia. Methods: A convenience sample of 10 healthy controls (CG) and 10 patients with haemophilia with elbow arthropathy (HG) participated in this study. Full ROM of elbow joints was measured in the frontal view with a 10‐degree sweep using: (a) a clinical goniometer; (b) the Kinect V2; (c) the Kinect V2 with angle correction; and (d) using a photograph. Bland‐Altman graphs (mean and 95% Limits of Agreement [LOA]) and Wilcoxon test were used to determine differences between measurements and groups. Results: The angle‐corrected Kinect V2 measurement removed the skew in the original data, reducing the average errors from 7.9° (LoA = −10.3°; 26.0°; CG) and 9.5° (LoA = −7.9°; 26.9°; HG) to −0.1° (LoA = −8.1°; 7.9°; CG) and −0.7° (LoA = −10.7°; 9.3°; HG). Conclusions: These error levels allow the use of Kinect V2 in the clinical practice. Kinect V2 with angle correction can complement the classical goniometry allowing an efficient and touchless measurement of ROM. [ABSTRACT FROM AUTHOR]

Background: The current therapeutics of morbid obesity could be significantly improved after the identification of novel biomarkers associated with the food addiction endophenotype of obesity and with bariatric surgery outcomes.Methods: We applied differential expression proteomics and enzyme-linked immunosorbent confirmatory assays to identify (a) proteins that varied according to loss of control over eating in morbidly obese patients and (b) proteins that varied between normoweight controls and patients before and 1 year after bariatric surgery.Results: Clusterin was the only protein that consistently varied according to eating control in patients. Patients showed increased levels of serum amyloid P protein, apolipoprotein A4, serotransferrin, complement factors B and C3 and haptoglobin with respect to controls; the levels of all these proteins tended to return to control values 1 year after surgery. In contrast, apolipoprotein A1 and transthyretin were initially downregulated in patients and were scarcely changed by surgery. Leucine-rich alpha-2-glycoprotein was markedly increased in patients only after surgery.Conclusions: Clusterin could be of interest as a putative biomarker for food addiction diagnosis in people with morbid obesity. In addition, postsurgical normalization of the proteins initially dysregulated in obese subjects might help monitor clinical improvements after surgery, while lasting or newly detected alterations (i.e., those affecting transthyretin and leucine-rich alpha-2-glycoprotein) could reflect partial refractoriness and/or contribute to the early prediction of clinical problems. [ABSTRACT FROM AUTHOR]

Permanent epicardial pacing wires are sometimes left in place and can lead to long‐term complications. We report on a case of a granulomatous reaction with a cutaneous fistula secondary to the retained epicardial pacing wires in a child and highlight the relevance of sonography as an additional tool in the diagnosis and management of dermatologic conditions. [ABSTRACT FROM AUTHOR]

In this study, rat models of wound closure by first and second intention were developed to evaluate the influence that two immunosuppressants for treating multiple sclerosis (fingolimod, azathioprine) have on wound healing. Sixty‐three Sprague‐Dawley rats were daily treated with fingolimod (0.6 mg/kg), azathioprine (2.5 mg/kg), or placebo (saline). Following 6 weeks of treatment, a linear incision (1.5 cm) or a circular excisional defect (diameter 1.5 cm) was made on the dorsal skin. The treatments were uninterrupted and after 7 days (incisional) or 21 days (incisional, excisional), animals were euthanized (n = 7 per group and time‐point). Morphometric (wound closure), histological (stainings), and immunofluorescent studies (macrophages) were performed to evaluate the healing process. For both the incisional and excisional defects, animals treated with fingolimod exhibited a healing process equivalent to that of placebo in terms of collagenization, wound closure, and macrophage response. By comparison, groups treated with azathioprine displayed a delay in healing times which was especially evident in the excisional defect, where inflammatory reaction and collagen deposition in the repair tissue remained active by day 21. These results show that immunosuppressants with a selective mechanism of action (fingolimod) can have less impact on wound healing than their classical nonselective counterparts (azathioprine). [ABSTRACT FROM AUTHOR]

Basan syndrome is a rare autosomal dominant genodermatosis, characterized by rapidly healing congenital acral bullae, congenital milia and adermatoglyphia (lack of finger and toeprints). This type of ectodermal dysplasia has been infrequently reported in the literature. A pathogenic mutation in the SMARCAD1 gene has been demonstrated to cause this rare disorder. [ABSTRACT FROM AUTHOR]

To the Editor, The resumption of activity in hospital practices after COVID-19 (SARS-CoV-2 infection) pandemic should be performed with the highest level of safety for both patients and healthcare professionals.1 The World Health Organization (WHO) declared COVID-19 pandemic on 11 March 2020 with temporary closures of medical specialties and cessation of many commercial activities still in effect to limit the spread of the disease.2 Spain is one of the European countries with the highest prevalence with 285,430 infected and almost 27,100 deaths due to the disease as of 30 July 2020. In our roles as allergists and health care providers, we must recognize the differences between allergic diseases and SARS-CoV-2, considering that the three PCR positive observed were patients consulting due to respiratory allergic symptoms. Signs and symptoms to determine if a patient presenting in primary care or hospital outpatient settings has COVID-19 disease. [Extracted from the article]

Raynaud's phenomenon (RP) is an episodic vasospastic response to cold or emotional stress causing color changes and pain. These attacks can lead to digital ischemia, ulcers, and gangrene. Severe and refractory RP in children is a therapeutic challenge for clinicians because there are no standardized treatment protocols for these patients. We present a case of RP involving the toes of a child successfully treated with botulinum toxin A. [ABSTRACT FROM AUTHOR]

Zhu‐Tokita‐Takenouchi‐Kim (ZTTK) syndrome is a rare, severe, and recently described multisystem developmental disorder characterized by delayed psychomotor development and intellectual disability, characteristic facial features, hypotonia, poor overall growth, and visual abnormalities. Mucocutaneous manifestations have not been reported so far among individuals with ZTTK syndrome. Herein, we present a patient with ZTTK syndrome due to a de novo mutation in SON gene, who has dental abnormalities and retronychia of the toenails. We suggest that mucocutaneous features may be a part of the phenotype. [ABSTRACT FROM AUTHOR]

Background: Recent reports indicate that tufted angioma is a rare vascular neoplasm that manifests more frequently at birth than previously thought. Few studies specifically address congenital presentation. Objectives: We analyzed the clinicopathological characteristics, clinical course, and treatment of congenital tufted angioma (cTA) and evaluated variables that were indicative of problematic lesions. Methods: We performed an observational retrospective study of 30 patients with cTA in 9 Spanish hospitals over a 14‐year period. Histopathology and immunohistochemistry studies were performed. Results: Congenital tufted angioma mainly affected the limbs (56.67%), followed by the face and/or neck (23.33%). Almost three‐quarters of facial cTA were located over the mandibular area. Immunohistochemically, proliferating cells expressed markers of endothelial cells, with some clusters of cells, especially at the periphery of the aggregates, showing positivity for podoplanin. As no associated complications were observed in 66.67% of cases, no treatment was started. Limitations: Data were collected retrospectively. Conclusions: Our findings emphasize the clinical features and course of cTA. The possibility of cTA should be considered when a poorly defined congenital infiltrative vascular tumor with(out) overlying hirsutism appears over the mandibular area. Location on the face and/or neck requires a more comprehensive workup, since potentially severe complications often appear early. [ABSTRACT FROM AUTHOR]

Abstract: High‐frequency ultrasonography is a bedside tool increasingly used for the assessment of skin lesions, but there have been few reports about its importance in children with skin signs of hematologic disease. We present three cases to highlight the usefulness of high‐frequency ultrasonography in assisting with the diagnosis of these skin lesions. [ABSTRACT FROM AUTHOR]

Abstract: The present paper reports on a case study performed on the Museum of Calatayud's educational program where the latter is showcased as a didactic model for the museumization of archaeological remains in the Iberian Peninsula (museum and site). This research has been developed by the Spanish Heritage Education Observatory (SHEO) in conjunction with the University of Zaragoza's CIVITAS project. The study shows a qualitative approach and is based on the comprehensive evaluation of the program's educational design and implementation resulting from a previous analysis of a sample consisting of N = 223 educational programs on archeological heritage. The evaluation has been conducted by using the SHEO method, whose aim is to gain deeper insights into educational practices by means of a standards‐based assessment of their underlying designs. Following the results of this study, the Museum of Calatayud appears as a clear benchmark: an institution that stands out because of its holistic conception and an approach that addresses issues of symbolism and identity in order to raise the population's awareness of its legacy and the importance of education inspired by heritage‐related values of respect and protection. Our research enables us to draw up a decalogue of key actions which we do not mean to be transferable to other contexts, but rather to provide an example or a starting point for future educational designs and implementations by the museum community and heritage institutions. [ABSTRACT FROM AUTHOR]

Abstract: Mercury (Hg) is a toxic trace element known to highly accumulate in aquatic biota and uptake by algae is the main entry‐point into the aquatic food chain. However, the effect of changes in solar irradiance and climatic conditions on Hg uptake by algae is largely unknown. We analyzed the link between sediment Hg accumulation, cyclic changes in total solar irradiance (TSI), and related changes in lake productivity as well as climate during the past 4.5 thousand years (kyr) in sediments of a small highly productive lake in Southern Patagonia (53°S). The analyses encompass proxies for TSI (based on 10Be), sediment geochemical composition, and lake productivity (FTIR spectra, and hydrogen‐index). The sediment record shows high concentrations of organic matter (median 70%) and strong variations in Hg accumulation rates (14–53 μg m2 yr−1) which correspond to changes in aquatic productivity and TSI. Accumulation of Hg was highest during dryer periods when irradiance and lake productivity was high. During these periods, accumulation was up to fourfold higher compared to those of lower TSI, lower productivity, and wetter climatic conditions. Higher amounts of algae biomass can increase Hg scavenging by organic particles and Hg export to the sediment. To obtain mass balance, we assume that the increase in sediment Hg accumulation rates during periods of lower Hg fluxes from the catchment (drier) caused a decrease in water phase Hg and in rates of Hg evasion from the lake. [ABSTRACT FROM AUTHOR]

We combine high-resolution soil sampling with lead (Pb) analyses (concentrations and stable isotopes) in two temperate podzols, together with previous data obtained with selective Al and Fe dissolution techniques. We aim to assess how atmospheric Pb is incorporated into the soils during pedogenesis. Partial least squares modelling for Pb concentrations shows that the podzolization process has the largest effect on Pb concentration (80·3% of the variance). The proportion of inorganic secondary compounds, the input of fresh organic matter from the soil surface and the relative abundance of Fe versus Al are responsible for a small part of the Pb concentration variance. Lead isotopic composition (206Pb/207Pb ratios) depends on soil organic matter content either fresh/poorly humified (57·3% of the variance) or humified (24·7% of the variance). The Pb linked to inorganic compounds and the overall podzolization process play a minor role in isotopic signature (5·3 and 3·7% of the variance respectively). Soil pH appears to be the controlling variable of the different transport and retention mechanisms. The relatively low isotopic ratios observed in spodic horizons result from geogenic Pb released through the preferential dissolution of the isotopically distinct most weatherable minerals of the parent material in the eluvial horizons, which undergoes downward mobilization. An accurate knowledge of soil reactive components and formation mechanisms is essential to a correct diagnose of the scope of Pb pollution and a more effective design of remediation strategies. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Aims This study examines the intraperitoneal behavior of two cyanoacrylate tissue adhesives: Ifabond® and a new, non-marketed octyl cyanoacrylate adhesive (OCA) used for the intraperitoneal fixation of a laminar expanded polytetrafluoroethylene (ePTFE) mesh. Material and Methods: In 36 New Zealand White rabbits, 3 × 3 cm ( n = 24) or 1.5 × 3 cm ( n = 12) fragments of ePTFE mesh (Preclude®, Gore, Flagstaff, USA) were fixed to the parietal peritoneum using OCA or Ifabond®. Peritoneal fluid was obtained at the time of implant and at 2 weeks postimplant for determination of the cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). At 14 or 90 days postsurgery, the animals were euthanized and the meshes excised to assess host tissue incorporation, the macrophage response, apoptosis and fixation strength (T-peel tensiometry). Results: Peritoneal fluid IL-6 and TNF-α concentrations were similar in the OCA and Ifabond® groups. Both adhesives gave rise to adequate mesothelialization of the laminar ePTFE. Macrophage counts were similar for the two study groups, but a significantly increase in macrophage response was observed from 14 to 90 days for Ifabond®. At 90 days postimplant, apoptotic cell counts was lower for the implants fixed with OCA and a fixation strength was significantly lower for OCA. Conclusions: Despite similar cytokine levels at 2 weeks and similar host tissue incorporation observed for the meshes fixed with the two adhesives, the use of Ifabond® gave rise to a greater apoptosis rate, although this adhesive provided a stronger fixation bond. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 312-319, 2017. [ABSTRACT FROM AUTHOR]

High‐frequency ultrasonography (HFUS) can help improve dermatofibrosarcoma protuberans (DFSP) recognition. We present three cases of DFSP in which a "jellyfish‐like" sonographic pattern was a useful adjunct in formulating the diagnosis. In addition, we review all DFSP ultrasound images available in the literature. [ABSTRACT FROM AUTHOR]

The effect of long-alkyl-chain amines in CuI-assisted azide-alkyne cycloadditions of terminal alkynes with organic azides in glycerol and other environmentally benign solvents (water, ethanol) has been examined. The presence of these additives favors the in situ formation of CuI-based nanoparticles and results in an increase of the catalytic reactivity. In glycerol, liquid-phase transmission electron microscopy (TEM) analyses, enabled by the negligible vapor pressure of this solvent, proved that CuI nanoparticles are responsible for the observed catalytic activity. The wide variety of alkynes and azides of which this effect has been investigated (14 combinations) confirms the role played by these additives in Cu-catalyzed Huisgen cycloadditions. [ABSTRACT FROM AUTHOR]