Delineating redox cooperativity in water-soluble and membrane multiheme cytochromes through protein design.

Nature has evolved diverse electron transport proteins and multiprotein assemblies essential to the generation and transduction of biological energy. However, substantially modifying or adapting these proteins for user-defined applications or to gain fundamental mechanistic insight can be hindered by their inherent complexity. De novo protein design offers an attractive route to stripping away this confounding complexity, enabling us to probe the fundamental workings of these bioenergetic proteins and systems, while providing robust, modular platforms for constructing completely artificial electron-conducting circuitry. Here, we use a set of de novo designed mono-heme and di-heme soluble and membrane proteins to delineate the contributions of electrostatic micro-environments and dielectric properties of the surrounding protein medium on the inter-heme redox cooperativity that we have previously reported. Experimentally, we find that the two heme sites in both the water-soluble and membrane constructs have broadly equivalent redox potentials in isolation, in agreement with Poisson-Boltzmann Continuum Electrostatics calculations. BioDC, a Python program for the estimation of electron transfer energetics and kinetics within multiheme cytochromes, also predicts equivalent heme sites, and reports that burial within the low dielectric environment of the membrane strengthens heme-heme electrostatic coupling. We conclude that redox cooperativity in our diheme cytochromes is largely driven by heme electrostatic coupling and confirm that this effect is greatly strengthened by burial in the membrane. These results demonstrate that while our de novo proteins present minimalist, new-to-nature constructs, they enable the dissection and microscopic examination of processes fundamental to the function of vital, yet complex, bioenergetic assemblies.

A Novel Technique for Substrate Toughening in Wood Single Lap Joints Using a Zero-Thickness Bio-Adhesive.

In contemporary engineering practices, the utilization of sustainable materials and eco-friendly techniques has gained significant importance. Wooden joints, particularly those created with polyurethan-based bio-adhesives, have garnered significant attention owing to their intrinsic environmental advantages and desirable mechanical properties. In comparison to conventional joining methods, adhesive joints offer distinct benefits such as an enhanced load distribution, reduced stress concentration, and improved aesthetic appeal. In this study, reference and toughened single-lap joint samples were investigated experimentally and numerically under quasi-static loading conditions. The proposed research methodology involves the infusion of a bio-adhesive into the wooden substrate, reinforcing the matrix of its surfaces. This innovative approach was developed to explore a synergetic effect of both wood and bio-adhesive. The experimentally validated results showcase a significant enhancement in joint strength, demonstrating an 85% increase when compared to joints with regular pine substrates. Moreover, the increased delamination thickness observed in toughened joints was found to increase the energy absorption of the joint.

Fatores relacionados com as crenças e atitudes face à amamentação dos adolescentes vítimas de maus-tratos que residem em instituições de acolhimento residencial / Factors related to the beliefs and attitudes towards breastfeeding of adolescent victims of abuse living in residential care institutions

Introdução: Os maus-tratos perpetrados contra crianças e adolescentes colocam em risco o seu adequado crescimento e desenvolvimento. Estudos indicam que a amamentação pode desempenhar um papel protetor no que diz respeito à perpetração dos maus-tratos infantojuvenis. As crenças e atitudes face à amamentação na adolescência podem ter influência na decisão futura de amamentar. Objetivos: Descrever as crenças e atitudes de adolescentes vítimas de maus-tratos que residem em instituições de acolhimento residencial face à amamentação; Estudar a relação entre a autoestima de adolescentes vítimas de maus-tratos que residem em instituições de acolhimento residencial e as crenças e atitudes face à amamentação; Estudar a relação entre variáveis sociodemográficas e as crenças e atitudes de adolescentes vítimas de maus-tratos que residem em instituições de acolhimento residencial face à amamentação. Metodologia: Estudo quantitativo, descritivo- correlacional, com uma amostra de 92 adolescentes vítimas de maus-tratos que residem em instituições de acolhimento residencial com idades compreendidas entre os 12 e os 19 anos. A colheita de informação, realizada de 30 de setembro de 2022 a 1 de fevereiro de 2023, foi concretizada através do preenchimento de um questionário de caracterização sociodemográfica, da Escala de Autoestima de Rosenberg e da Escala de Crenças e Atitudes face à amamentação. Resultados: Adolescentes do sexo masculino, mais novos, com menos escolaridade e que foram vítimas de maus-tratos durante menos tempo apresentaram crenças e atitudes face à amamentação mais negativas. Apurou-se também que foram os adolescentes vítimas de negligência que apresentaram crenças e atitudes face à amamentação mais negativas. Foram as raparigas e os adolescentes com maior escolaridade que apresentaram maior perceção das barreiras sociais face à amamentação. Observou-se ainda que o nível de autoestima dos adolescentes vítimas de maus-tratos que residem em instituições de acolhimento residencial não tem relação com as suas crenças e atitudes face à amamentação. Conclusão: É necessário o investimento em mais estudos de investigação no que diz respeito à temática das crenças e atitudes face à amamentação dos adolescentes vítimas de maus-tratos que residem em instituições de acolhimento residencial.

A terapia da dignidade: uma intervenção especializada no conforto da pessoa em situação paliativa / Dignity therapy: a specialised intervention to comfort people in a palliative situation

Ao longo dos últimos anos, temos assistido a um aumento da esperança média de vida e o consequente envelhecimento populacional, aliados ao aumento da prevalência de doenças crónicas. Isto leva-nos a refletir sobre o fim de vida, e sobre a necessidade de conforto e qualidade de vida até ao último momento. Portanto, emerge a necessidade de Cuidados Paliativos (CP), que têm o objetivo o alívio do sofrimento físico, psicológico, social e espiritual, com base na identificação precoce e no tratamento rigoroso da dor e outros sintomas físicos, mas também psicossociais e espirituais, das pessoas que são portadoras de uma doença incurável e/ou grave, progressiva e avançada assim como as suas famílias ou pessoas significativas. Neste sentido, dando continuidade ao processo de aprendizagem, optou-se por realizar o estágio num serviço de cuidados paliativos de um hospital central com o objetivo de desenvolver competências comuns e específicas de enfermeiro especialista na área da enfermagem à pessoa em situação paliativa. O presente relatório do Estágio de Natureza Profissional contempla a descrição e análise critico-reflexiva das atividades realizadas e as competências adquiridas ao longo do mesmo. Para dar resposta aos objetivos propostos, das atividades desenvolvidas destacam-se o estudo de investigação, que se debruçou sobre a dimensão espiritual, ­concretamente sobre a Terapia da Dignidade (TD) no doente em cuidados paliativos. Neste sentido realizou-se uma scoping review, com o objetivo de mapear os efeitos da terapia da dignidade em doentes em cuidados paliativos. Os principais resultados mostram que esta terapia produz efeitos benéficos a nível espiritual, psi-emocional, físico, social e da própria qualidade de vida. Com este estudo percebeu-se que a TD tem efeitos bastante positivos no alívio do sofrimento do doente em situação de fim de vida pelo que pode ser considerada uma estratégia útil no âmbito dos cuidados paliativos tornando-os em cuidados cada vez mais dignos, humanizados e com um olhar holístico sobre o doente e a família. A nível do desenvolvimento de competências comuns, nomeadamente nas competências de gestão e formação, destacam-se nas atividades realizadas a elaboração de uma "Proposta de Protocolo de Apoio no Luto", e ainda à realização de duas formações "Dignidade em Fim de Vida" e "Apoio no Luto" dando resposta as necessidades da equipa e do serviço onde foi realizado o estágio. A nível do desenvolvimento de competências específicas, as atividades assentaram nas dimensões essenciais dos CP, nomeadamente: gestão de sintomas; comunicação; trabalho em equipa, apoio à família e apoio no luto, respeitando os princípios éticos, deontológicos e legais. Concluindo, verifica-se a necessidade de continuar a concetualizar e desenvolver cuidados paliativos especializados, nomeadamente pelo enfermeiro especialista em enfermagem à pessoa em situação paliativa, através da inclusão de estratégias sustentadas na melhor evidência, tais como a terapia da dignidade, e assim, proporcionar cuidados mais dignos ao doente e família, com o propósito de os ajudar a um melhor entendimento das formas de alívio de sofrimento na sua fase final de vida.

Over the last few years, we have witnessed an increase in life expectancy and the subsequent aging of the population, along with the rise in the prevalence of chronic diseases. This leads us to reflect on the end of life and the need for comfort and quality of life until the last moment. Thus, the need for palliative care arises. Palliative care's goal is the relief of physical pain, psychological, social and spiritual suffering for people diagnosed with an incurable and/or severe, progressive and advanced disease and their families or close friends. To achieve this, it uses early identification and rigorous treatment of pain and other physical, psychosocial and spiritual symptoms. In this sense, continuing the learning process, it was chosen to carry out the internship in a palliative care service at a central hospital aiming to develop common and specific specialist nurse skills in the field of nursing for individuals in palliative situations. This Professional Nature Internship report includes the description and critical-reflexive analysis of the activities carried out and the competencies acquired throughout the internship. To address the proposed objectives, among the activities carried out, the research study is highlighted, which focused on the spiritual dimension - specifically on Dignity Therapy (DT) in palliative care patients. In this regard, a scoping review was conducted aiming to map the effects of Dignity Therapy (DT) on patients in palliative care. The main findings show that this therapy has beneficial effects on the spiritual, psychosocial, physical, social, and overall quality of life aspects. Through this study, it was understood that DT has highly positive effects in relieving the suffering of patients in end-of-life situations, making it a valuable strategy within palliative care, which contributes to providing increasingly dignified, humanized care, with a holistic approach to the patient and their family. Regarding the development of common competencies, namely in management and training skills, the activities undertaken included the creation of a "Proposal for a Bereavement Support Protocol." Additionally, two training sessions were conducted on "Dignity at the End of Life" and "Bereavement Support," addressing the needs of the team and the service where the internship took place. Regarding the development of specific competencies, the activities focused on the essential dimensions of palliative care, including symptom management, communication, teamwork, family support, and bereavement support, adhering to ethical, deontological, and legal principles. In conclusion, there is a need to continue conceptualizing and developing specialized palliative care, particularly by the nurses specialized in nursing for individuals in palliative situations, through the incorporation of evidence-based strategies, such as dignity therapy, to provide more dignified care for patients and their families, aiming to help them better understand ways to alleviate suffering in their end-of-life phase.

Improvement of Processability Characteristics of Porcelain-Based Formulations Toward the Utilization of 3D Printing Technology.

A study of the feasibility of porcelain-based formulations for 3D printing was performed. Based on commercial materials characterization, the binder jetting process properties requirements were defined. Porcelain powder-based formulations were prepared and evaluated with different binder solutions. The powder-binder formulations were characterized (e.g., particle size distribution and wettability of powder, viscosity and surface tension of liquid binder) and showed some different and similar characteristics when compared with commercial materials. The addition of solid (sodium alginate, sucrose) and liquid (glycerol, ethanol) additives in the powder-binder composition improved the experimental printed tests. The effect of binder composition and operating process parameters (binder saturation level, bleed compensation, and printed layer thickness) was analyzed and optimized to obtain a printed saucer with different designs. Results revealed some limitations related to the materials and the technology, thus justifying the introduction of technological improvements. This study showed the possibility to process industrial porcelain powders by additive manufacturing, paving the way for a new development challenge in the productive process of ceramic products.

A contenção mecânica na pessoa idosa em contexto hospitalar / Mechanical restraint in the elderly in a hospital context

A contenção mecânica pode ser definida como qualquer ação ou procedimento que impede os movimentos do corpo de uma pessoa através de qualquer método que lhe esteja adjacente ou anexado e que ela não consiga controlar ou remover facilmente. É uma medida que tem como objetivo otimizar a segurança do doente e de quem o rodeia, contudo a sua utilização é por vezes indevida, causando complicações físicas e psicológicas e comprometendo a dignidade, liberdade e autonomia das pessoas a ela submetidas. Alguns fatores de risco associados a uma maior predisposição para a colocação de medidas de contenção mecânica incluem a idade avançada, alterações cognitivas, incontinência e dependência nas atividades de vida diárias, tornando a população idosa particularmente vulnerável a ser submetida a estas medidas. Estes aspetos complexificam a tomada de decisão que no caso particular dos enfermeiros, é tida como um processo de deliberação ética que envolve a manutenção da integridade física, psicológica e moral da pessoa idosa. Deste modo, definiu-se como finalidade para este projeto contribuir para a melhoria dos cuidados de enfermagem à pessoa idosa submetida a contenção mecânica em contexto hospitalar. De forma a atingir esta finalidade e os objetivos propostos foram planeadas três atividades: a prestação de cuidados de enfermagem direta a pessoais idosas com fatores de risco para a contenção mecânica; a participação na elaboração e implementação do estudo de investigação com o objetivo estruturar um plano de melhoria que promova a segurança da pessoa idosa em risco de contenção mecânica em contexto hospitalar e a capacitação dos profissionais de saúde para a tomada de decisão em relação à utilização de medidas de contenção mecânica na pessoa idosa. Este relatório visa demonstrar o percurso realizado ao longo do estágio, que consistiu num processo de aprendizagem para a aquisição e desenvolvimento de competências especializadas, no que respeita às competências de enfermeiro mestre e especialista em enfermagem médico-cirúrgica.

Physical restraint can be defined as any action or procedure that impedes the movement of a person's body through any method that is adjacent or attached to it, and that the person cannot easily control or remove. It is a measure that aims to optimize patient's safety and those around him, however its use is at times inappropriate, causing physical and psychological complications and compromising the dignity, freedom and autonomy of the people subjected to it. Some risk factors associated with a greater predisposition to the placement of physical restraint measures include advanced age, cognitive alterations, incontinence and dependence in daily activities, making the elderly population particularly vulnerable to being subjected to these measures. These aspects complicate decision-making which, in the particular case of nurses, is seen as a process of ethical deliberation that involves maintaining the physical, psychological and moral integrity of the elderly patient. Thus, the purpose of this project was defined as contributing to the improvement of nursing care for the elderly subject to physical restraint in hospital context. In order to achieve this purpose and the proposed objectives, three activities were planned: the provision of direct nursing care to elderly people with risk factors for physical restraint; participation in the preparation and implementation of the research study with the goal of structuring an improvement plan that promotes the safety of the elderly at risk of physical restraint in the hospital context and training of health professionals to make decisions regarding the use of measures of physical restraint in the elderly. This report aims to demonstrate the path taken during the internship, which consisted of a learning process for the acquisition and development of specialized skills, with regard to the skills of master nurse and specialist in medical-surgical nursing.

Different factors are associated with changing body composition in people living with HIV.

INTRODUCTION: Antiretroviral Therapy (ART) gives people living with HIV/AIDS (PLWHA) a new perspective of life, although some develop changes in impaired body composition. This study aimed to assess the factors associated with changes in body composition in PLWHA using ART, depending food consumption. MATERIAL AND METHODS: It was a cross-sectional study and took place through interviews with patients treated at an University Hospital. Secondary data: CD4+ T cells, ART time and age. The level of physical activity and smoking were self-reported. For the assessment of body composition, electrical bioimpedance and measurements of weight, height and waist circumference were used. RESULTS: The highest percentages of fat mass and fat-free mass, in treatment for more than 5 years, were in the female group (p <0.01), aged> 50 years (p = 0.02) and in the male group (p <0.01), young adult (p <0.01), respectively. The final linear regression model for both free fat mass and fat mass had sex, age, smoking and nutritional diagnosis as relevant factors. The frequency of food consumption was inadequate for calories, carbohydrates, proteins and lipids was high, however it did not significantly influence body composition. CONCLUSIONS: Gender, age, smoking and nutritional diagnosis by BMI significantly influence body composition.

Comparing randomized controlled trials of outpatient family-based or inpatient multimodal treatment followed by outpatient care in youth with anorexia nervosa: Differences in populations, metrics, and outcomes.

OBJECTIVE: Various approaches exist to treat youth with anorexia nervosa (AN). Family-based treatment (FBT) has never been compared to long inpatient, multimodal treatment (IMT) in a randomized controlled trial (RCT). The aim of this study was to compare data on body weight trajectories, change in eating disorder psychopathology, hospital days and treatment costs in RCTs delivering FBT or IMT. METHOD: Review of RCTs published between 2010 and 2020 in youth with AN, delivering FBT or IMT. RESULTS: Four RCTs delivering FBT (United States, n = 2; Australia, n = 2), one RCT delivering Family Therapy for AN (United Kingdom) and two RCTs delivering IMT (France, n = 1; Germany, n = 1) were identified from previous meta-analyses. The comparison of studies was limited by (1) significant differences in patient baseline characteristics including pretreated versus non-pretreated patients, (2) use of different psychometric and weight measures and (3) different initial velocity of weight recovery. Minimal baseline and outcome reporting standards for body weight metrics and nature/dose of interventions allowing international comparison are needed and suggestions to developing these standards are presented. DISCUSSION: An RCT should investigate, whether FBT is a viable alternative to IMT, leading to comparable weight and psychopathology improvement with less inpatient time and costs.

Adherence to antiretroviral therapy and changes in body composition in people living with HIV and AIDS / Adesão a terapia antirretroviral e alterações da composição corporal em pessoas vivendo com HIV/AIDS

Introduction: The successful treatment of human immunodeficiency virus (HIV) infection depends on adherence to antiretroviral therapy. Since the development of ART, there has been a significant increase in the survival of people living with HIV/AIDS. However, in the same way that it works in a positive way, the antiretroviral therapy has side effects that ultimately influence the rate of adherence to drug treatment. Objective: Evaluate adherence to antiretroviral therapy (ART) and changes in the body composition of adults diagnosed with HIV/AIDSon ART for at least 12 months. Methods: A cross-sectional study was conducted at an outpatient clinic for infectious-parasitic diseases at a teaching hospital that is a reference in the treatment of people living with HIV/ AIDS. Socio-demographic and clinical data were collected from medical records. Weight, height, body mass index (BMI) and abdominal circumference (AC) were recorded. Bioelectrical impedance analysis was performed using the tetrapolar protocol to assess body composition. The "Cuestionario para la Evaluación de la Adhesión al Tratamiento Antiretroviral" was used to investigate adherence to ART. Results: Sixty-one patients (27 women and 33 men) participated in the study. Most were more than 40 years of age and were classified as overweight based on BMI. Most patients (86.8%) had been using ART for more than five years and 78.6% were classified as sedentary. Among the patients with an adequate AC, 82.3% were men. Among the 11 patients with low adherence to ART, 90.9% were men. Among the 33 with strict adherence, 69.6% were women. Mean percentage of fat mass was 28.63% among the men, and 40.82% among the women. Conclusion: Strict adherence to ART was seen in more than half of the study population. Women had more side effects from ART, as this group hadgreater adherence to treatment. The findings underscore the relationship between high rates of adherence to ART and changes in body composition, such as increased fat deposition and risk of associated diseases.

Introdução: O sucesso do tratamento da infecção pelo vírus da imunodeficiência humana (HIV) depende da adesão à terapia antirretroviral (TARV). Desde o desenvolvimento da TARV, houve aumento significativo da sobrevida das pessoas que vivem com HIV/Síndrome da Imunodeficiência Adquirida (AIDS). Porém, da mesma forma que atua de modo positivo, a terapia antirretroviral possui efeitos colaterais que acabam influenciando a taxa de adesão terapêutica ao tratamento medicamentoso. Esses efeitos incluem significativas alterações na composição corporal, resistência à insulina e dislipidemias. Objetivo: Avaliar a adesão à terapia antirretroviral e descrever alterações na composição corporal de adultos com diagnóstico de HIV/AIDS que usaram terapia antirretroviral por no mínimo 12 meses. Métodos: Estudo transversal realizado em um ambulatório de doenças infectoparasitárias em Hospital Universitário, referência no tratamento de pessoas que vivem com HIV/AIDS. Verificou-se dados sociodemográficos e clínicos nos prontuários. Foram registrados peso, altura, índice de massa corporal (IMC) e circunferência abdominal (CA). Realizou-se a bioimpedância segundo o protocolo da técnica tetrapolar para avaliação da composição corporal. Para avaliar a adesão terapêutica foi usado o Cuestionario para la Evaluación de la Adhesión al Tratamiento Antiretroviral. Resultados: Foram estudados 61 pacientes, 27 mulheres e 34 homens; a maior parte tinha acima de 40 anos e IMC classificado como sobrepeso. A maioria dos pacientes (86,8%) usavam TARV há mais de cinco anos e 78,6% se autodeclararam sedentários. Do total de pacientes que apresentaram circunferência abdominal adequada, 82,3% eram homens. Dos 11 pacientes que se classificaram como baixa adesão à TARV, 90,9% eram homens, e dos 33 que se classificaram como estritamente aderentes, 69,6% eram mulheres. Os homens apresentaram 28,63% de média de porcentual de massa gorda (%MG), enquanto as mulheres apresentaram 40,82%. Conclusão: A adesão estrita à TARV foi vista em mais da metade da população estudada. As mulheres apresentaram mais efeitos colaterais oriundos da TARV, visto que este grupo mostrou uma adesão maior ao tratamento. Isso reforça a relação entre altas taxas de adesão à terapia medicamentosa e alterações na composição corporal, como o aumento da deposição de gordura e riscos de doenças associadas.

#COVIDisAirborne: AI-Enabled Multiscale Computational Microscopy of Delta SARS-CoV-2 in a Respiratory Aerosol

We seek to completely revise current models of airborne transmission of respiratory viruses by providing never-before-seen atomic-level views of the SARS-CoV-2 virus within a respiratory aerosol. Our work dramatically extends the capabilities of multiscale computational microscopy to address the significant gaps that exist in current experimental methods, which are limited in their ability to interrogate aerosols at the atomic/molecular level and thus ob-scure our understanding of airborne transmission. We demonstrate how our integrated data-driven platform provides a new way of exploring the composition, structure, and dynamics of aerosols and aerosolized viruses, while driving simulation method development along several important axes. We present a series of initial scientific discoveries for the SARS-CoV-2 Delta variant, noting that the full scientific impact of this work has yet to be realized. ACM Reference FormatAbigail Dommer1{dagger}, Lorenzo Casalino1{dagger}, Fiona Kearns1{dagger}, Mia Rosenfeld1, Nicholas Wauer1, Surl-Hee Ahn1, John Russo,2 Sofia Oliveira3, Clare Morris1, AnthonyBogetti4, AndaTrifan5,6, Alexander Brace5,7, TerraSztain1,8, Austin Clyde5,7, Heng Ma5, Chakra Chennubhotla4, Hyungro Lee9, Matteo Turilli9, Syma Khalid10, Teresa Tamayo-Mendoza11, Matthew Welborn11, Anders Christensen11, Daniel G. A. Smith11, Zhuoran Qiao12, Sai Krishna Sirumalla11, Michael OConnor11, Frederick Manby11, Anima Anandkumar12,13, David Hardy6, James Phillips6, Abraham Stern13, Josh Romero13, David Clark13, Mitchell Dorrell14, Tom Maiden14, Lei Huang15, John McCalpin15, Christo- pherWoods3, Alan Gray13, MattWilliams3, Bryan Barker16, HarindaRajapaksha16, Richard Pitts16, Tom Gibbs13, John Stone6, Daniel Zuckerman2*, Adrian Mulholland3*, Thomas MillerIII11,12*, ShantenuJha9*, Arvind Ramanathan5*, Lillian Chong4*, Rommie Amaro1*. 2021. #COVIDisAirborne: AI-Enabled Multiscale Computational Microscopy ofDeltaSARS-CoV-2 in a Respiratory Aerosol. In Supercomputing 21: International Conference for High Perfor-mance Computing, Networking, Storage, and Analysis. ACM, New York, NY, USA, 14 pages. https://doi.org/finalDOI

The Role of Nutritional Status on Polypharmacy, Cognition, and Functional Capacity of Institutionalized Elderly: A Systematic Review.

Adequate nutritional status is necessary for the proper management of polypharmacy, the prevention of cognitive decline, and the maintenance of functional capacity in activities of daily living. Although several studies validate this fact for the general elderly population, data on institutionalized seniors concerning this relation are scarce. A systematic review was performed according to the PRISMA guidelines, aiming to study the potential correlation between nutritional status and polypharmacy, cognitive decline, and functional performance in institutionalized elders. The search was limited to studies in English or Portuguese in the last decade. Inclusion criteria relied on the PICO method. Five studies explored the relationship of nutritional status with cognitive performance in the institutionalized elderly, and nine prospective observational studies reported significant positive associations between appropriate nutritional status and physical abilities. Nutritional status was primarily measured by MNA. Adequate nutritional status was described as an important parameter in preventing cognitive and functional decline in the institutionalized elderly. No studies were found describing the impact of nutritional status on the prevention of polypharmacy. Given the strong impact of malnutrition found in the studies in cognition and functional abilities in the institutionalized elderly, an evaluation of nutritional status of the elders is crucial to prevent health problems and allow early intervention programs in order to further prevent health decline.

"How Come You Don't Call Me?" Smartphone Communication App Usage as an Indicator of Loneliness and Social Well-Being across the Adult Lifespan during the COVID-19 Pandemic.

Loneliness and lack of social well-being are associated with adverse health outcomes and have increased during the COVID-19 pandemic. Smartphone communication data have been suggested to help monitor loneliness, but this requires further evidence. We investigated the informative value of smartphone communication app data for predicting subjective loneliness and social well-being in a sample of 364 participants ranging from 18 to 78 years of age (52.2% female; mean age = 42.54, SD = 13.22) derived from the CORONA HEALTH APP study from July to December 2020 in Germany. The participants experienced relatively high levels of loneliness and low social well-being during the time period characterized by the COVID-19 pandemic. Apart from positive associations with phone call use times, smartphone communication app use was associated with social well-being and loneliness only when considering the age of participants. Younger participants with higher use times tended to report less social well-being and higher loneliness, while the opposite association was found for older adults. Thus, the informative value of smartphone communication use time was rather small and became evident only in consideration of age. The results highlight the need for further investigations and the need to address several limitations in order to draw conclusions at the population level.

The fatty acid site is coupled to functional motifs in the SARS-CoV-2 spike protein and modulates spike allosteric behaviour

The SARS-CoV-2 spike protein is the first contact point between the SARS-CoV-2 virus and host cells and mediates membrane fusion. Recently, a fatty acid binding site was identified in the spike (Toelzer et al. Science 2020). The presence of linoleic acid at this site modulates binding of the spike to the human ACE2 receptor, stabilizing a locked conformation of the protein. Here, dynamical-nonequilibrium molecular dynamics simulations reveal that this fatty acid site is coupled to functionally relevant regions of the spike, some of them far from the fatty acid binding pocket. Removal of a ligand from the fatty acid binding site significantly affects the dynamics of distant, functionally important regions of the spike, including the receptor-binding motif, furin cleavage site and fusion-peptide-adjacent regions. The results also show significant differences in behaviour between clinical variants of the spike: e.g. the D614G mutation shows a significantly different conformational response for some structural motifs relevant for binding and fusion. The simulations identify structural networks through which changes at the fatty acid binding site are transmitted within the protein. These communication networks significantly involve positions that are prone to mutation, indicating that observed genetic variation in the spike may alter its response to linoleate binding and associated allosteric communication.

Evaluation of Cocoa Bean Shell Antimicrobial Activity: A Tentative Assay Using a Metabolomic Approach for Active Compound Identification.

Cocoa bean shell is one of the main by-products of chocolate manufacturing and possesses several compounds with biofunctionalities. It can function as an antibacterial agent, and its action is mostly reported against Streptococcus mutans. However, only a few studies have investigated the cocoa bean shell compounds responsible for this activity. This study aimed to evaluate several extracts of cocoa bean shells from different geographical origins and cocoa varieties and estimate their antimicrobial properties against different fungal and bacterial strains by determining their minimal inhibitory concentration. The results demonstrated antimicrobial activity of cocoa bean shell against one of the tested strains, S. mutans. Cocoa bean shell extracts were further analysed via LC-HRMS for untargeted metabolomic analysis. LC-HRMS data were analysed (preprocessing and statistical analyses) using the Workflow4Metabolomics platform. The latter enabled us to identify possible compounds responsible for the detected antimicrobial activity by comparing the more and less active extracts. Active extracts were not the most abundant in polyphenols but contained higher concentrations of two metabolites. After tentative annotation of these metabolites, one of them was identified and confirmed to be 7-methylxanthine. When tested alone, 7-methylxanthine did not display antibacterial activity. However, a possible cocktail effect due to the synergistic activity of this molecule along with other compounds in the cocoa bean shell extracts cannot be neglected. In conclusion, cocoa bean shell could be a functional ingredient with benefits for human health as it exhibited antibacterial activity against S. mutans. However, the antimicrobial mechanisms still need to be confirmed.

Proposals for Antimicrobial Testing Guidelines Applied on Ajowan and Spanish Lavender Essential Oils.

To fight the rising resistance of microorganisms to antibiotics, a strategy followed by several researchers is to focus on natural compounds, such as essential oils, as a source of potent antibacterial compounds. These last decades, hundreds of original papers have been written about microbiological assays that prove the antibacterial activity of essential oils and their use in the medical field. But can we really compare all the data available in the literature when the raw material, the microbiological assays, and/or the strains are different from one article to another? This review will point out the differences and the inadequate practices found in published articles that tested 2 lesser-studied essential oils-Spanish lavender and the ajowan-by the broth dilution method against Staphylococcus aureus, a human pathogenic bacterium. Many pitfalls were found in the literature, for example, a variable chemical composition rarely underlined by the authors, unidentified strains or clinical strains used without a related antibiogram, a lack of quality controls, and the assertion of questionable positive results. At last, some general guidelines that should be followed by every scientific researcher will be discussed.

Consumption of antidiabetic medicines in Portugal: results of a temporal data analysis of a thirteen-year study (2005-2017).

BACKGROUND: Studies of drug utilization in patients with diabetes, a chronic disease that can be treated with a wide range of available medicines, have attracted substantial social and clinical interest. OBJECTIVE: To characterize antidiabetic medicine consumption between 2005 and 2017, to evaluate the trends of these medicines in mainland Portugal, and to compare district consumption. An additional objective was to perform a statistical analysis on drug consumption in different regions of Portugal. METHODS: A descriptive, longitudinal observational study; the setting was mainland Portugal ( excluding Azores and Madeira). Each medicine has a respective defined daily dose (DDD). The sum of the DDD, provides the annual consumption in terms of the DDD for each district each year. When calculating the annual average for the resident district population and the number of days in a year, the denominator is expressed as 1000 inhabitants per day (TID). MAIN OUTCOME MEASURE: The DDD/TID for mainland Portugal (for all districts) between 2005 and 2017 for antidiabetic medicines. Information was obtained from the official database of prescription medicine invoices with reimbursement in mainland Portugal. RESULTS: In mainland Portugal, the antidiabetic medicine consumption was 49.3 DDD/TID in 2005 and 88.2 DDD/TID in 2017. The consumption of insulins and their analogs increased from 10.8% to 17.4% compared to the total consumption of antidiabetic medicines. In 2017, the level of biguanide consumption was 23.1 DDD/TID, that of sulphonylurea consumption was 15.8 DDD/TID, that of DPP-4 inhibitor consumption was 6.8 DDD/TID, and that of SGLT2 inhibitor consumption was 3.0 DDD/TID. The oral consumption of fixed-dose combinations reached 21.4 DDD/TID. After employing a geographical division between north and south and between coastal and inland regions, the consumption of several different drugs showed statistically significant differences. CONCLUSIONS: When comparing 2017 with 2005, the panorama was quite different, with higher levels of consumption of antidiabetic medicines, insulins and their analogs, noninsulin medicines, long-acting and fast-acting insulins and their analogs, metformin, DPP-4 inhibitors and, mainly, metformin combined with a DPP-4 inhibitor. The SGLT2 inhibitors achieved a representative consumption. Different consumption patterns may be related to sociodemographic factors or to clinical practices.

A statistical model to identify determinants of glycemic control in patients with type 2 diabetes with different pharmacotherapeutic profiles.

AIM: To develop a statistical model to identify determinants of glycemic control. MATERIALS AND METHODS: A database was extracted from patients' records with at least one glycated hemoglobin (HbA1c) analysis and with antidiabetic therapy established and stabilized. A logistic regression model was designed to identify the statistical significance of factors associated with glycemic control. RESULTS: Higher probability of success (HbA1c ≤8% [64 mmol/mol]) was found for those who were older in age, those who were men, and those with higher education levels. Increased values for the following variables were associated with the poorest glycemic control: number of years of T2DM since diagnosis, number of antidiabetic medicines, body mass index, low-density lipoprotein cholesterol, triglycerides, systolic blood pressure and number of diabetes consultations in the last twelve months. The following pharmacotherapeutic treatments were associated with glycemic control (in decreasing order of the results): oral antidiabetic drugs; oral antidiabetic drugs and insulin; insulin. Patients using metformin and a dipeptidyl peptidase-4 inhibitors have a higher probability of success than do patients using metformin and a sulfonylurea, and patients using insulin and metformin have a higher probability of success than do patients using insulin alone. CONCLUSIONS: Sociodemographic, clinical and therapeutic parameters can strongly affect glycemic control. Studies based on real-life patient data provide important information on the development of more effective glycemic control.

Simulations support the interaction of the SARS-CoV-2 spike protein with nicotinic acetylcholine receptors and suggest subtype specificity

Changeux et al. recently suggested that the SARS-CoV-2 spike (S) protein may interact with nicotinic acetylcholine receptors (nAChRs). Such interactions may be involved in pathology and infectivity. Here, we use molecular simulations of validated atomically detailed structures of nAChRs, and of the S protein, to investigate this nicotinic hypothesis. We examine the binding of the Y674-R685 loop of the S protein to three nAChRs, namely the human 4{beta}2 and 7 subtypes and the muscle-like {beta}{gamma}d receptor from Tetronarce californica. Our results indicate that Y674-R685 has affinity for nAChRs and the region responsible for binding contains the PRRA motif, a four-residue insertion not found in other SARS-like coronaviruses. In particular, R682 has a key role in the stabilisation of the complexes as it forms interactions with loops A, B and C in the receptors binding pocket. The conformational behaviour of the bound Y674-R685 region is highly dependent on the receptor subtype, adopting extended conformations in the 4{beta}2 and 7 complexes and more compact ones when bound to the muscle-like receptor. In the 4{beta}2 and {beta}{gamma}d complexes, the interaction of Y674-R685 with the receptors forces the loop C region to adopt an open conformation similar to other known nAChR antagonists. In contrast, in the 7 complex, Y674-R685 penetrates deeply into the binding pocket where it forms interactions with the residues lining the aromatic box, namely with TrpB, TyrC1 and TyrC2. Estimates of binding energy suggest that Y674-R685 forms stable complexes with all three nAChR subtypes. Analyses of the simulations of the full-length S protein show that the Y674-R685 region is accessible for binding, and suggest a potential binding orientation of the S protein with nAChRs.

Sudden Onset of Severe Cervical Pain in an Adolescent Girl: Case Report and Review of Literature.

A previously healthy 13-year-old girl presented with a 9-day history of acute onset severe neck pain associated with limited range of movement. Medical evaluation at day 2 was suggestive of muscle contracture, and she was discharged home with diazepam, antiinflammatory agents, and rest; however, she returned because of progressive clinical worsening with left arm distal paresthesia and paralysis since day 3. There was no history of trauma or other systemic complaints, and her familial medical history was unremarkable.Physical examination revealed left cervical and paravertebral tenderness on palpation with severe limitation of cervical and trunk movements; neurologic examination revealed left forearm and hand weakness and paralysis (grade II/V) with thenarhypothenar atrophy. Laboratory studies including coagulation profile were normal. Magnetic resonance imaging revealed an epidural hematoma from C4-T1 without underlying cause apparent on magnetic resonance angiography. On day 12, she underwent C3-7 laminotomy with laminoplasty and complete drainage of the hematoma. After 5 months of follow-up, she displays no neurological deficits. The spontaneous spinal epidural hematoma is a rare neurosurgical emergency in children. It usually presents acutely with neurologic deficits, but the initial presentation may be atypical or insidious, delaying diagnosis and intervention. Definitive diagnosis is made by magnetic resonance imaging and implies a high index of suspicion. Surgical drainage of the hematoma is the mainstay of treatment with favorable prognosis even in cases with a delayed diagnosis.