Meralgia Paresthetica: A Report of a Rare Case.

Meralgia paresthetica (MP) is a painful condition caused by damage or constriction of the lateral femoral cutaneous nerve (LFCN). This entrapment condition typically arises due to various factors, including trauma, pelvic tumors, external compression from belts or snug attire, and weight gain. The prognosis is generally favorable since most cases are self-limiting or respond to conservative treatment. We present the case of a 53-year-old overweight man, with no relevant medical history, who was a victim of a traffic accident in October 2023 which resulted in polytrauma, according to the Case Reports (CARE) checklist. The main complaint of the patient was tingling of the left thigh, with dysesthesia to gentle rubbing along the anterolateral surface. After a diagnostic study, a diagnosis of post-trauma MP was thus established, probably due to seat-belt compression of the LFCN, and physiatric treatment was initiated. With the assistance of ultrasound, a large hematoma was seen, above the inguinal ligament with drainage of 140ccc of serosanguineous fluid with resolution of the symptoms. This case emphasizes the importance of a physiatry consultation for a correct diagnosis and focuses on the main complaint of a polytrauma patient.

Long-term colchicine for the prevention of vascular recurrent events in non-cardioembolic stroke (CONVINCE): a randomised controlled trial.

BACKGROUND: Anti-inflammatory therapy with long-term colchicine prevented vascular recurrence in coronary disease. Unlike coronary disease, which is typically caused by atherosclerosis, ischaemic stroke is caused by diverse mechanisms including atherosclerosis and small vessel disease or is frequently due to an unknown cause. We aimed to investigate the hypothesis that long-term colchicine would reduce recurrent events after ischaemic stroke. METHODS: We did a randomised, parallel-group, open-label, blinded endpoint assessed trial comparing long-term colchicine (0·5 mg orally per day) plus guideline-based usual care with usual care only. Hospital-based patients with non-severe, non-cardioembolic ischaemic stroke or high-risk transient ischaemic attack were eligible. The primary endpoint was a composite of first fatal or non-fatal recurrent ischaemic stroke, myocardial infarction, cardiac arrest, or hospitalisation (defined as an admission to an inpatient unit or a visit to an emergency department that resulted in at least a 24 h stay [or a change in calendar date if the hospital admission or discharge times were not available]) for unstable angina. The p value for significance was 0·048 to adjust for two prespecified interim analyses conducted by the data monitoring committee, for which the steering committee and trial investigators remained blinded. The trial was registered at ClinicalTrials.gov (NCT02898610) and is completed. FINDINGS: 3154 patients were randomly assigned between Dec 19, 2016, and Nov 21, 2022, with the last follow-up on Jan 31, 2024. The trial finished before the anticipated number of outcomes was accrued (367 outcomes planned) due to budget constraints attributable to the COVID-19 pandemic. Ten patients withdrew consent for analysis of their data, leaving 3144 patients in the intention-to-treat analysis: 1569 (colchicine and usual care) and 1575 (usual care alone). A primary endpoint occurred in 338 patients, 153 (9·8%) of 1569 patients allocated to colchicine and usual care and 185 (11·7%) of 1575 patients allocated to usual care alone (incidence rates 3·32 vs 3·92 per 100 person-years, hazard ratio 0·84; 95% CI 0·68-1·05, p=0·12). Although no between-group difference in C-reactive protein (CRP) was observed at baseline, patients treated with colchicine had lower CRP at 28 days and at 1, 2, and 3 years (p<0·05 for all timepoints). The rates of serious adverse events were similar in both groups. INTERPRETATION: Although no statistically significant benefit was observed on the primary intention-to-treat analysis, the findings provide new evidence supporting the rationale for anti-inflammatory therapy in further randomised trials. FUNDING: Health Research Board Ireland, Deutsche Forschungsgemeinschaft (German Research Foundation), and Fonds Wetenschappelijk Onderzoek Vlaanderen (Research Foundation Flanders), Belgium.

Analyzing Linear and Angular Deviations After Guided Surgery for Dental Implant Placement: A Preliminary Study.

PURPOSE: This study aimed to assess the accuracy and precision of prosthetically-driven implant placement achieved through static computer-aided implant surgery. The primary objective was to analyze the linear and angular deviations of dental implants in patients treated at a university dental clinic. Various types of surgical techniques and templates were utilized to optimize implant positioning. MATERIALS AND METHODS: A total of fiftythree dental implants were included in this study. The implants were positioned using either tooth-supported templates or tooth-tissue-supported templates with fixation pins. Two distinct guided surgery approaches were used, these being pilot drill guided and fully guided. Three-dimensional (3D) data from the implant planning phase was superimposed with the 3D data from the final implant positions using the 'Treatment Evaluation' tool within CoDiagnostix. implant planning software (Straumann AG). This enabled the automatic calculation of deviations in implant placement accuracy. RESULTS: Average angular deviation observed was 3.90 degrees. For linear deviations, the mean 3D deviation at the most coronal point of the implants was 1.04 mm, while at the implant apex it was 1.56 mm. CONCLUSION: This research demonstrates the feasibility of a digital workflow for guided implant surgery, offering a promising treatment option. Nonetheless, it is important to note that deviations do occur, with the apical region of the implant being the most affected area. Care should be taken, particularly in cases of limited bone availability.

A conceptual framework to help choose appropriate blue nature-based solutions.

Biodiversity loss and climate change have severely impacted ecosystems and livelihoods worldwide, compromising access to food and water, increasing disaster risk, and affecting human health globally. Nature-based Solutions (NbS) have gained interest in addressing these global societal challenges. Although much effort has been directed to NbS in urban and terrestrial environments, the implementation of NbS in marine and coastal environments (blue NbS) lags. The lack of a framework to guide decision-makers and practitioners through the initial planning stages appears to be one of the main obstacles to the slow implementation of blue NbS. To address this, we propose an integrated conceptual framework, built from expert knowledge, to inform the selection of the most appropriate blue NbS based on desired intervention objectives and social-ecological context. Our conceptual framework follows a four incremental steps structure: Step 1 aims to identify the societal challenge(s) to address; Step 2 highlights ecosystem services and the underlying biodiversity and ecological functions that could contribute to confronting the societal challenge(s); Step 3 identify the specific environmental context the intervention needs to be set within (e.g. the spatial scale the intervention will operate within, the ecosystem's vulnerability to stressors, and its ecological condition); and Step 4 provides a selection of potential blue NbS interventions that would help address the targeted societal challenge(s) considering the context defined through Step 3. Designed to maintain, enhance, recover, rehabilitate, or create ecosystem services by supporting biodiversity, the blue NbS intervention portfolio includes marine protection (i.e., fully, highly, lightly, and minimally protected areas), restorative activities (i.e., active, passive, and partial restoration; rehabilitation of ecological function and ecosystem creation), and other management measures (i.e., implementation and enforcement of regulation). Ultimately, our conceptual framework guides decision-makers toward a versatile portfolio of interventions that cater to the specific needs of each ecosystem rather than imposing a rigid, one-size-fits-all model. In the future, this framework needs to integrate socio-economic considerations more comprehensively and be kept up-to-date by including the latest scientific information.

A 96-wells fluidic system for high-throughput screenings under laminar high wall shear stress conditions.

The ability of endothelial cells to respond to blood flow is fundamental for the correct formation and maintenance of a functional and hierarchically organized vascular network. Defective flow responses, in particular related to high flow conditions, have been associated with atherosclerosis, stroke, arteriovenous malformations, and neurodegenerative diseases. Yet, the molecular mechanisms involved in high flow response are still poorly understood. Here, we described the development and validation of a 96-wells fluidic system, with interchangeable cell culture and fluidics, to perform high-throughput screenings under laminar high-flow conditions. We demonstrated that endothelial cells in our newly developed 96-wells fluidic system respond to fluid flow-induced shear stress by aligning along the flow direction and increasing the levels of KLF2 and KLF4. We further demonstrate that our 96-wells fluidic system allows for efficient gene knock-down compatible with automated liquid handling for high-throughput screening platforms. Overall, we propose that this modular 96-well fluidic system is an excellent platform to perform genome-wide and/or drug screenings to identify the molecular mechanisms involved in the responses of endothelial cells to high wall shear stress.

Unraveling the In Vitro Toxicity Profile of Psychedelic 2C Phenethylamines and Their N-Benzylphenethylamine (NBOMe) Analogues.

Mescaline derivative (2C phenethylamines) drugs have been modified by the introduction of a N-2-methoxybenzyl group to originate a new series of compounds with recognized and potent psychedelic effects, the NBOMe-drugs. Although they are prevalent in unregulated drug markets, their toxicity profile is still poorly understood, despite several reports highlighting cases of acute intoxication, with brain and liver toxicity. Thus, in this study, mescaline, 2C-N (insertion of a nitro in the para position of the 2C phenethylamines aromatic ring) and 2C-B (insertion of a bromide in the para position of the 2C phenethylamines aromatic ring) and their corresponding NBOMe counterparts, mescaline-NBOMe, 25N-NBOMe and 25B-NBOMe, were synthetized and the in vitro neuro- and hepatocytotoxicity evaluated in differentiated SH-SY5Y and HepG2 cell lines, respectively. Cytotoxicity, oxidative stress, metabolic and energetic studies were performed to evaluate the main pathways involved in their toxicity. Our results demonstrated that the presence of the N-2-methoxybenzyl group significantly increased the in vitro cytotoxicity of 2C phenethylamines drugs in both cell lines, with the NBOMe drugs presenting lower EC50 values when compared to their counterparts. Consistently, our data showed a correlation between the drug's lipophilicity and the EC50 values, except for 2C-B. The 2C-B presented higher cytotoxic effects in both cell lines than mescaline-NBOMe, a result that can be explained by its higher passive permeability. All the NBOMe derivatives were able to cross the blood-brain barrier. Considering metabolic studies, the cytotoxicity of these drugs was shown to be influenced by inhibition of cytochrome P450 (CYP), which suggests a potential role of this enzyme complex, especially CYP3A4 and CYP2D6 isoenzymes in SH-SY5Y cells, in their detoxification or bioactivation. Furthermore, in differentiated SH-SY5Y cells, the drugs were able to induce mitochondrial membrane depolarization, and to disrupt GSH and ATP intracellular levels, these effects being concentration dependent and more pronounced for the NBOMe derivatives. No ROS overproduction was detected for any of the drugs in the tested experimental conditions. A correlation between a drug's lipophilicity and the EC50 values in both cell lines, except for 2C-B, was also obtained. In summary, the introduction of a NBOMe moiety to the parent drugs significantly increases their lipophilicity, brain permeability and cytotoxic effects, with GSH and ATP homeostasis disruption. The inhibition of CYP3A4 and CYP2D6 emphasized that CYP-mediated metabolism impacts the toxicity of these drugs.

Upper Airway Assessment in Cone-Beam Computed Tomography for Screening of Obstructive Sleep Apnea Syndrome: Development of an Evaluation Protocol in Dentistry.

BACKGROUND: The upper airways are formed by the nasal cavities, pharynx, and larynx. There are several radiographic methods that allow evaluation of the craniofacial structure. Upper airway analysis in cone-beam computed tomography (CBCT) may be useful in diagnosing some pathologies such as obstructive sleep apnea syndrome (OSAS). OSAS prevalence has increased significantly in recent decades, justified by increased obesity and average life expectancy. It can be associated with cardiovascular, respiratory, and neurovascular diseases, diabetes, and hypertension. In some individuals with OSAS, the upper airway is compromised and narrowed. Nowadays, CBCT is widely used in dentistry by clinicians. Its use for upper airway assessment would be an advantage for screening some abnormalities related to an increased risk of pathologies such as OSAS. CBCT helps to calculate the total volume of the airways and their area in different anatomical planes (sagittal, coronal, and transverse). It also helps identify regions with the highest anteroposterior and laterolateral constriction of the airways. Despite its undoubted advantages, airway assessment is not routinely performed in dentistry. There is no protocol that allows comparisons between studies, which makes it difficult to obtain scientific evidence in this area. Hence, there is an urgent need to standardize the protocol for upper airway measurement to help clinicians identify at-risk patients. OBJECTIVE: Our main aim is to develop a standard protocol for upper airway evaluation in CBCT for OSAS screening in dentistry. METHODS: To measure and evaluate the upper airways, data are obtained using Planmeca ProMax 3D (Planmeca). Patient orientation is performed in accordance with the manufacturer's indications at the time of image acquisition. The exposure corresponds to 90 kV, 8 mA, and 13,713 seconds. The software used for upper airway analysis is Romexis (version 5.1.O.R; Planmeca). The images are exhibited in accordance with the field of view of 20.1×17.4 cm, size of 502×502×436 mm, and voxel size of 400 µm. RESULTS: The protocol described and illustrated here allows for automatic calculation of the total volume of the pharyngeal airspace, its area of greatest narrowing, its location, and the smallest anteroposterior and laterolateral dimensions of the pharynx. These measurements are carried out automatically by the imaging software whose reliability is proven by the existing literature. Thus, we could reduce the possible bias of manual measurement, aiming at data collection. CONCLUSIONS: The use of this protocol by dentists will allow for standardization of the measurements and constitutes a valuable screening tool for OSAS. This protocol may also be suitable for other imaging software. The anatomical points used as reference are most relevant for standardizing studies in this field. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/41049.

Survey data of public awareness on climate change and the value of marine and coastal ecosystems.

The long-term provision of ocean ecosystem services depends on healthy ecosystems and effective sustainable management. Understanding public opinion about marine and coastal ecosystems is important to guide decision-making and inform specific actions. However, available data on public perceptions on the interlinked effects of climate change, human impacts and the value and management of marine and coastal ecosystems are rare. This dataset presents raw data from an online, self-administered, public awareness survey conducted between November 2021 and February 2022 which yielded 709 responses from 42 countries. The survey was released in four languages (English, French, Spanish and Italian) and consisted of four main parts: (1) perceptions about climate change; (2) perceptions about the value of, and threats to, coasts, oceans and their wildlife, (3) perceptions about climate change response; and (4) socio-demographic information. Participation in the survey was voluntary and all respondents provided informed consent after reading a participant information form at the beginning of the survey. Responses were anonymous unless respondents chose to provide contact information. All identifying information has been removed from the dataset. The dataset can be used to conduct quantitative analyses, especially in the area of public perceptions of the interlinkages between climate change, human impacts and options for sustainable management in the context of marine and coastal ecosystems. The dataset is provided with this article, including a copy of the survey and participant information forms in all four languages, data and the corresponding codebook.

Evaluating the combined effect of climate and anthropogenic stressors on marine coastal ecosystems: Insights from a systematic review of cumulative impact assessment approaches.

Cumulative impacts increasingly threaten marine and coastal ecosystems. To address this issue, the research community has invested efforts on designing and testing different methodological approaches and tools that apply cumulative impact appraisal schemes for a sound evaluation of the complex interactions and dynamics among multiple pressures affecting marine and coastal ecosystems. Through an iterative scientometric and systematic literature review, this paper provides the state of the art of cumulative impact assessment approaches and applications. It gives a specific attention to cutting-edge approaches that explore and model inter-relations among climatic and anthropogenic pressures, vulnerability and resilience of marine and coastal ecosystems to these pressures, and the resulting changes in ecosystem services flow. Despite recent advances in computer sciences and the rising availability of big data for environmental monitoring and management, this literature review evidenced that the implementation of advanced complex system methods for cumulative risk assessment remains limited. Moreover, experts have only recently started integrating ecosystem services flow into cumulative impact appraisal frameworks, but more as a general assessment endpoint within the overall evaluation process (e.g. changes in the bundle of ecosystem services against cumulative impacts). The review also highlights a lack of integrated approaches and complex tools able to frame, explain, and model spatio-temporal dynamics of marine and coastal ecosystems' response to multiple pressures, as required under relevant EU legislation (e.g., Water Framework and Marine Strategy Framework Directives). Progress in understanding cumulative impacts, exploiting the functionalities of more sophisticated machine learning-based approaches (e.g., big data integration), will support decision-makers in the achievement of environmental and sustainability objectives.

MesopTroph, a database of trophic parameters to study interactions in mesopelagic food webs.

Mesopelagic organisms play a crucial role in marine food webs, channelling energy across the predator-prey network and connecting depth strata through their diel vertical migrations. The information available to assess mesopelagic feeding interactions and energy transfer has increased substantially in recent years, owing to the growing interest and research activity in the mesopelagic realm. However, such data have not been systematically collated and are difficult to access, hampering estimation of the contribution of mesopelagic organisms to marine ecosystems. Here we present MesopTroph, a georeferenced database of diet, trophic markers, and energy content of mesopelagic and other marine taxa compiled from 203 published and non-published sources. MesopTroph currently includes data on stomach contents, carbon and nitrogen stable isotopes, major and trace elements, energy density, fatty acids, trophic positions, and diet proportion estimates for 498 species/genera. MesopTroph will be expanded with new data emerging from ongoing studies. MesopTroph provides a unique tool to investigate trophic interactions and energy flow mediated by mesopelagic organisms, and to evaluate the ecosystem services of this community.

Competition for endothelial cell polarity drives vascular morphogenesis in the mouse retina.

Blood-vessel formation generates unique vascular patterns in each individual. The principles governing the apparent stochasticity of this process remain to be elucidated. Using mathematical methods, we find that the transition between two fundamental vascular morphogenetic programs-sprouting angiogenesis and vascular remodeling-is established by a shift of collective front-to-rear polarity of endothelial cells in the mouse retina. We demonstrate that the competition between biochemical (VEGFA) and mechanical (blood-flow-induced shear stress) cues controls this collective polarity shift. Shear stress increases tension at focal adhesions overriding VEGFA-driven collective polarization, which relies on tension at adherens junctions. We propose that vascular morphogenetic cues compete to regulate individual cell polarity and migration through tension shifts that translates into tissue-level emergent behaviors, ultimately leading to uniquely organized vascular patterns.

Aerocyte specification and lung adaptation to breathing is dependent on alternative splicing changes.

Adaptation to breathing is a critical step in lung function and it is crucial for organismal survival. Alveoli are the lung gas exchange units and their development, from late embryonic to early postnatal stages, requires feedbacks between multiple cell types. However, how the crosstalk between the alveolar cell types is modulated to anticipate lung adaptation to breathing is still unclear. Here, we uncovered a synchronous alternative splicing switch in multiple genes in the developing mouse lungs at the transition to birth, and we identified hnRNP A1, Cpeb4, and Elavl2/HuB as putative splicing regulators of this transition. Notably, we found that <i>Vegfa</i> switches from the <i>Vegfa</i> 164 isoform to the longer <i>Vegfa</i> 188 isoform exclusively in lung alveolar epithelial AT1 cells. Functional analysis revealed that VEGFA 188 (and not VEGFA 164) drives the specification of Car4-positive aerocytes, a subtype of alveolar endothelial cells specialized in gas exchanges. Our results reveal that the cell type-specific regulation of <i>Vegfa</i> alternative splicing just before birth modulates the epithelial-endothelial crosstalk in the developing alveoli to promote lung adaptation to breathing.

Saberes e adesão às boas práticas de higienização das mãos pelos profissionais de saúde / Knowledge and adherence to good hand hygiene practices by health professionals

As Infeções Associadas aos Cuidados de Saúde são um problema que atinge dimensões significativas, com implicações na morbilidade, na mortalidade, nos custos para doentes, famílias e sociedade e na qualidade dos cuidados de saúde. Enquanto medida simples e económica. A higienização das mãos é apontada como estratégia primordial para a prevenção destas infeções, cuja prática constitui um dever cívico, ético e profissional de todos os profissionais de saúde. Com base nestes pressupostos, o presente estudo pretendeu avaliar a variação dos conhecimentos sobre a higienização das mãos, e a adesão à prática da higienização das mãos, em função do grupo profissional. Para tal, desenvolveu-se um estudo descritivo-correlacional e transversal com uma população de 56 profissionais de saúde, de uma unidade de cuidados continuados do norte de Portugal. O instrumento de colheita de dados foi construído com base numa grelha de observação normalmente utilizada nas auditorias de avaliação (DGS, 2016). Assim, para a avaliação dos conhecimentos dos profissionais utilizou-se um questionário, e para a avaliação da adesão à higienização das mãos a observação. A aplicação dos instrumentos de recolha permitiu concluir que o conhecimento dos profissionais é satisfatório, sendo mais evidente no que se refere à forma correta de procedimento da fricção antissética (98,21%), à principal via de transmissão (89,3%), à necessidade de evitar joias, acessórios (80,4%) e unhas postiças (83,9%), ao método a aplicar em diferentes circunstâncias (75%) e ao tempo mínimo necessário para realização da higienização com SABA (73,2%). Não é tão significativo no que respeita à fonte mais frequente de microrganismos responsáveis pela IACS, assim como a pormenores que implicam uma técnica correta de higienização, nomeadamente lesões de pele (39,3%). Entre os diferentes grupos de profissionais o dos enfermeiros é aquele que apresenta um maior número de respostas corretas, seguido pelo dos assistentes operacionais, apesar de não se encontrarem diferenças estatisticamente significativas. A taxa de adesão à prática da higienização das mãos foi de 64,02%, com variação entre 28,57% e 94,12%, tendo sido superior nos enfermeiros, em comparação com o grupo dos médicos (p=0,00), dos técnicos de diagnóstico e terapêutica (p=0,00) e dos assistentes operacionais (p=0,00). Em síntese os conhecimentos são satisfatórios e a adesão à higienização é baixa, com diferenças entre os grupos profissionais o que comprova a necessidade de um contínuo investimento na formação, para se atingirem taxas de adesão mais elevadas e mais segurança nos cuidados.

Health care-associated infections are a problem that affects significant dimensions, with implications on morbidity, mortality, costs for patients, family and society, and in the quality of health care. Hand hygiene is seen as a primary strategy to prevent these infections, and its practice consists of a civic, ethical and professional duty of all healthcare professionals. Based on these premises, the present study aimed to assess the variation in knowledge about hand hygiene, as well as in the adherence to hand hygiene practice, according to professional group. To accomplish that, we carried out a descriptive-correlational and cross-sectional study, with a population of 56 healthcare professionals, from a continuous care unit from the north of Portugal. The data collection instrument was built on the basis of an observation grid normally used in assessment audits (DGS, 2016). Thus, to assess the professionals' knowledge a questionnaire was used, and to assess adherence to hygiene hands we used the observation technique. The application of the collection instruments allowed us to conclude that the professionals' knowledge is satisfactory, especially about the correct antiseptic friction procedure (98,21%), the main way of transmission (89,3%), the need to avoid jewelry, accessories (80,4%) and nail extensions (83,9%), the method to be applied in different circumstances (75%), and the minimum time required to clean with SABA (73,2%). However, the professionals' knowledge is not so significant with regard to the most frequent source of microorganisms responsible for health care-associated infections, as well as in details that demand a correct hygiene technique, namely skin lesions (39,3%). Between the different groups of professionals, the nurses' is the one that presents the highest number of correct answers, followed by the group of operational assistants, although there are no statistically significant differences. The rate of adherence to the practice of hand hygiene was 64,02%, but it varies widely between 28,57% and 94,12%. The rate was higher in nurses, compared to the group of doctors (p = 0,00), diagnostic and therapeutic technicians (p = 0,00) and operational assistants (p = 0,00). In summary, the professionals' knowledge is satisfactory and adherence to hygiene is low, with differences between professional groups, which substantiates the need for continuous investment in the training of professionals, in order to achieve higher adherence rates and more safety in care.

Endothelial cells on the move: dynamics in vascular morphogenesis and disease.

The vascular system is a hierarchically organized network of blood vessels that play crucial roles in embryogenesis, homeostasis and disease. Blood vessels are built by endothelial cells - the cells lining the interior of blood vessels - through a process named vascular morphogenesis. Endothelial cells react to different biomechanical signals in their environment by adjusting their behavior to: (1) invade, proliferate and fuse to form new vessels (angiogenesis); (2) remodel, regress and establish a hierarchy in the network (patterning); and (3) maintain network stability (quiescence). Each step involves the coordination of endothelial cell differentiation, proliferation, polarity, migration, rearrangements and shape changes to ensure network integrity and an efficient barrier between blood and tissues. In this review, we highlighted the relevance and the mechanisms involving endothelial cell migration during different steps of vascular morphogenesis. We further present evidence on how impaired endothelial cell dynamics can contribute to pathology.

A coin crisis: a case report of pica with minireview.

BACKGROUND: Pica is defined as a feeding and eating disorder where there is consumption of nonnutritive substances not consistent with cultural practices or social norms. Its aetiology is still unknown, as its prevalence and optimal treatment, which seem to vary with patients' characteristics and the specific behaviours involved. OBJECTIVES: The authors present a case report of pica treated with copper supplementation, with further diagnostic and treatment considerations. METHODS: Clinical records and interviews were used. A review was conducted using PubMed database. RESULTS: A 59-year-old patient, diagnosed with paranoid schizophrenia, presented with sideroblastic anaemia secondary to zinc-induced copper deficiency in the context of pica. These behaviours ceased with copper supplementation. After 2-year remission, the patient was discontinued on oral copper. One week after, pica behaviours reoccurred, with further remission with renewed copper treatment. Based on temporal relationship, we propose that there might be an association between copper supplementation and pica, not related to its plasma levels. CONCLUSIONS: As far as we know, this is the first case report in the literature with such a long-term follow-up of pica treatment. Our findings challenge the cause-effect relation between micronutrient deficiency and pica and prompts further research in the non-adaptive theories of this poorly understood clinical entity.

Characteristics of lactose-free frozen yogurt with κ-carrageenan and corn starch as stabilizers.

Frozen yogurt is a type of dairy product that is considered to be a more healthful alternative to conventional ice cream due to its lower fat content and the presence of viable lactic acid bacteria. Lactose-free products are a growing trend in the dairy industry, and lactose-free yogurts and ice creams can both be found on the market. However, lactose-free frozen yogurt has not yet reached the market. In this study, we aimed to investigate the effect of adding κ-carrageenan (0.05, 0.1, and 0.15%) and corn starch (1, 2, and 3%) on acidity, texture, viscosity, overrun, melting properties, color attributes, and sensory characteristics of lactose-free frozen yogurts. Lactose was reduced by enzymatic hydrolysis during the fermentation process. The effectiveness of the hydrolysis was measured by HPLC, and lactose was reduced to 0.05% after 80 min of incubation with the enzyme. The addition of stabilizers did not change overrun and melting properties of frozen yogurt, but it did affect pH, titratable acidity, and color parameters. The product with 0.15% κ-carrageenan had the highest hardness and stickiness values. Moreover, κ-carrageenan had a positive effect on sensory attractiveness of lactose-free frozen yogurt, and it reduced the coarse texture in comparison with the control without stabilizers. A lactose-free frozen yogurt with good quality and nutritional characteristics was produced, particularly with the use of κ-carrageenan as stabilizer.

Non-canonical Wnt signaling regulates junctional mechanocoupling during angiogenic collective cell migration.

Morphogenesis of hierarchical vascular networks depends on the integration of multiple biomechanical signals by endothelial cells, the cells lining the interior of blood vessels. Expansion of vascular networks arises through sprouting angiogenesis, a process involving extensive cell rearrangements and collective cell migration. Yet, the mechanisms controlling angiogenic collective behavior remain poorly understood. Here, we show this collective cell behavior is regulated by non-canonical Wnt signaling. We identify that Wnt5a specifically activates Cdc42 at cell junctions downstream of ROR2 to reinforce coupling between adherens junctions and the actin cytoskeleton. We show that Wnt5a signaling stabilizes vinculin binding to alpha-catenin, and abrogation of vinculin in vivo and in vitro leads to uncoordinated polarity and deficient sprouting angiogenesis in Mus musculus. Our findings highlight how non-canonical Wnt signaling coordinates collective cell behavior during vascular morphogenesis by fine-tuning junctional mechanocoupling between endothelial cells.

Etiologic Evaluation of Ischemic Stroke in Young Adults: A Comparative Study between Two European Centers.

INTRODUCTION: Identifying the cause of ischemic stroke in young adults is often difficult. Our objective was to compare the etiologic diagnostic strategy for ischemic stroke in young adults between 2 European centers and investigate the influence of workup variations in the diagnosed etiologies. PATIENTS AND METHODS: We included patients aged 18-55 years admitted for ischemic stroke or transient ischemic attack to the stroke units of Santa Maria Hospital in Lisbon, Portugal, and Innsbruck University Hospital in Innsbruck, Austria, between 2014 and 2016. Etiology and diagnostic procedures were compared between centers. RESULTS: We included 156 patients from Innsbruck University Hospital and 110 patients from Santa Maria Hospital. Search for intracranial large-vessel disease was performed mainly by computed tomography/magnetic resonance angiography in Innsbruck (83.9% versus 52.7%; P < .01) and by transcranial Doppler in Lisbon (91.8% versus 43.2%; P < .01). Transoesophageal echocardiography was preferred in Innsbruck for detecting paradoxical embolism (80.0% versus 68.2%; P < .05), whereas in Lisbon contrast transcranial Doppler was preferred (80.9% versus 3.9%; P < .01). For investigation of other causes, Lisbon patients were more commonly screened for thrombophilia (100.0% versus 92.3%; P < .05) and autoimmune disorders (91.7% versus 44.5%; P < .01) while in Innsbruck consultation by other specialists was more frequent (51.6% versus 10.0%; P < .01). No significant differences were found in etiologies between centers. CONCLUSION: The differences in diagnostic workup did not influence etiologic diagnosis. Extensive laboratory testing does not seem to influence diagnosis of stroke of other determined cause, emphasizing the importance of a clinically-oriented approach for the etiologic diagnosis of stroke in young adults.

Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Triggers, Causes, and Outcome (SECRETO): Rationale and design.

BACKGROUND: Worldwide, about 1.3 million annual ischaemic strokes (IS) occur in adults aged <50 years. Of these early-onset strokes, up to 50% can be regarded as cryptogenic or associated with conditions with poorly documented causality like patent foramen ovale and coagulopathies. KEY HYPOTHESES/AIMS: (1) Investigate transient triggers and clinical/sub-clinical chronic risk factors associated with cryptogenic IS in the young; (2) use cardiac imaging methods exceeding state-of-the-art to reveal novel sources for embolism; (3) search for covert thrombosis and haemostasis abnormalities; (4) discover new disease pathways using next-generation sequencing and RNA gene expression studies; (5) determine patient prognosis by use of phenotypic and genetic data; and (6) adapt systems medicine approach to investigate complex risk-factor interactions. DESIGN: Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO; NCT01934725) is a prospective multi-centre case-control study enrolling patients aged 18-49 years hospitalised due to first-ever imaging-proven IS of undetermined etiology. Patients are examined according to a standardised protocol and followed up for 10 years. Patients are 1:1 age- and sex-matched to stroke-free controls. Key study elements include centralised reading of echocardiography, electrocardiography, and neurovascular imaging, as well as blood samples for genetic, gene-expression, thrombosis and haemostasis and biomarker analysis. We aim to have 600 patient-control pairs enrolled by the end of 2018. SUMMARY: SECRETO is aiming to establish novel mechanisms and prognosis of cryptogenic IS in the young and will provide new directions for therapy development for these patients. First results are anticipated in 2019.

Non-canonical Wnt signalling modulates the endothelial shear stress flow sensor in vascular remodelling.

Endothelial cells respond to molecular and physical forces in development and vascular homeostasis. Deregulation of endothelial responses to flow-induced shear is believed to contribute to many aspects of cardiovascular diseases including atherosclerosis. However, how molecular signals and shear-mediated physical forces integrate to regulate vascular patterning is poorly understood. Here we show that endothelial non-canonical Wnt signalling regulates endothelial sensitivity to shear forces. Loss of Wnt5a/Wnt11 renders endothelial cells more sensitive to shear, resulting in axial polarization and migration against flow at lower shear levels. Integration of flow modelling and polarity analysis in entire vascular networks demonstrates that polarization against flow is achieved differentially in artery, vein, capillaries and the primitive sprouting front. Collectively our data suggest that non-canonical Wnt signalling stabilizes forming vascular networks by reducing endothelial shear sensitivity, thus keeping vessels open under low flow conditions that prevail in the primitive plexus.