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Unfortunately, survivors of traumatic stress exposure (TSE) frequently develop adverse posttraumatic neuropsychiatric sequelae (APNS) such as chronic pain and stress/depressive symptoms. Increasing evidence indicates that there is a ‘window of opportunity’ following TSE in which therapeutic interventions are most effective against APNS, yet mechanisms accounting for this observation are poorly understood. Here, we aimed to better understand such mechanisms by generating snapshots of the transcriptional landscape in the early aftermath of TSE across tissues and time. Adult rats were exposed to a TSE model, single prolonged stress (SPS). Then, eight tissues (hypothalamus, left and right hippocampus, amygdala, dorsal root ganglia, spinal cord, heart, and muscle) were isolated from these animals at 2, 24, and 72 h after SPS and in unexposed controls ( n  = 6 per group). mRNA expression from deep sequencing was used to identify differentially expressed genes (DEGs), biological pathways enriched over time, and predicted upstream regulators. In all tissues except the amygdala, the highest number of DEGs was observed 2-h post-SPS, but DEGs were detected at all timepoints and in all tissues. Some transcripts were differentially expressed in a consistent manner across multiple tissues at a time point (e.g. Fkbp5 , 2 h post-SPS), while others had tissue- or region-specific expression patterns. Stress system pathways were most represented at 2 h post-SPS, then stress/circadian/inflammatory pathways at 24 h, and inflammatory pathways at 72 h. Together these findings provide insights into post-TSE transcriptional landscape dynamics and suggest specific intervention windows of opportunity. Future validation is needed across sex, age, stressor, and cell type.

(1) Background: Heart failure (HF) is a major cause of morbidity and mortality throughout the world. Despite substantial progress in its prevention and treatment, mortality rates remain high. Device therapy for HF mainly includes cardiac resynchronization therapy (CRT) and the use of an implantable cardioverter-defibrillator (ICD). Recently, however, a new device therapy—cardiac contractility modulation (CCM)—became available. (2) Aim: The purpose of this study is to present a first case-series of patients with different clinical patterns of HF with a reduced ejection fraction (HFrEF), supported with the newest generation of CCM devices. (3) Methods and results: Five patients with a left ventricular ejection fraction (LVEF) ≤ 35% and a New York Heart Association (NYHA) class ≥ III were supported with CCM OPTIMIZER® SMART IPGCCMX10 at our clinic. The patients had a median age of 67 ± 8.03 years (47–80) and were all males—four with ischemic etiology dilated cardiomyopathy. In two cases, CCM was added on top of CRT (non-responders), and, in one patient, CCM was delivered during persistent atrial fibrillation (AF). After 6 months of follow-up, the LVEF increased from 25.4 ± 6.8% to 27 ± 9%, and the six-minute walk distance increased from 310 ± 65.1 m to 466 ± 23.6 m. One patient died 47 days after device implantation. (4) Conclusion: CCM therapy provided with the new model OPTIMIZER® SMART IPG CCMX10 is safe, feasible, and applicable to a wide range of patients with HF.

Design and deployment of the manufacturing processes are based on complex data concerning product development, process structures, planning, costs. Applications within the computer-based engineering are conditioned by the information system. Storage and use of specific data are concentrating in databases. The present contribution is on the development of basic elements for creation a database system on turning processes, usable in engineering activities. The main part presents the information model that provides neutral data interfaces system for machining processes. Implemented under Microsoft Visual Basic macros, this database system supports the integration of manufacturing requests. Based on stored information and initial data provided by user, the designed database system offers variants of technological elements. Structures and relationships are provided.

Cutting tools selection is a very important and time consuming activity in production systems. It influences parts quality, productivity and timing, therefore production cost. Computer-based approach is conditioned by programming structures and information concentrated in databases. This paper presents the basic architecture and relationships for a tool selection management system in turning processes, which is under development. Relational implementation defined by internal links, is highlighted. The system is constructed using macros and Microsoft Visual Basic. Considering input data provided by user, different solutions for machines, toolholders and indexable inserts are generated. The database is designed to support manufacturing requests.

Today’s product designer is being asked to develop high quality at an ever increasing pace. To meet this need, an intensive search is underway for advanced design methodologies that facilitate the acquisition of design knowledge and creative ideas for later reuse. Additionally, designers are embracing a wide range of macros applications to increase their productivity. This paper proposes a solution for creating a group product database, this being under development, starting from the specifications product in an excel file, in the end obtaining the entities block for the products with parameters and actions according to their characteristics. The code it’s implemented for an abrasive tool by linking product definition parameters to CAD’s functions.

Unfortunately, survivors of traumatic stress exposure (TSE) frequently develop adverse posttraumatic neuropsychiatric sequelae (APNS) such as chronic pain and stress/depressive symptoms. Increasing evidence indicates that there is a 'window of opportunity' following TSE in which therapeutic interventions are most effective against APNS, yet mechanisms accounting for this observation are poorly understood. Here, we aimed to better understand such mechanisms by generating snapshots of the transcriptional landscape in the early aftermath of TSE across tissues and time. Adult rats were exposed to a TSE model, single prolonged stress (SPS). Then, eight tissues (hypothalamus, left and right hippocampus, amygdala, dorsal root ganglia, spinal cord, heart, and muscle) were isolated from these animals at 2, 24, and 72 hours after SPS and in unexposed controls (n=6 per group). mRNA expression from deep sequencing was used to identify differentially expressed genes (DEGs) and biological pathways enriched over time. In all tissues except the amygdala, the highest number of DEGs was observed 2-hours post-SPS, but DEGs were detected at all timepoints and in all tissues. Some transcripts were differentially expressed in a consistent manner across multiple tissues at a time point (e.g. Fkbp5, 2 hours post-SPS), while others had tissue- or region-specific expression patterns. Stress system pathways were most represented at 2-hours post-SPS, then stress/circadian/inflammatory pathways at 24-hours, and inflammatory pathways at 72-hours. Together these findings provide insights into post-TSE transcriptional landscape dynamics and suggest specific intervention windows of opportunity. Future validation is needed across sex, age, stressor, and cell type.

Chronic pain affects 20-30% of the population and imposes a significant socio-economic burden as it is often accompanied by substantial emotional comorbidities such as anxiety and depression. Yet, the mechanisms underlying the interactions between the sensory and emotional aspects of chronic pain remain poorly understood. Here, we investigated the role of FKBP51, a regulator of the stress response, in mediating both sensory and emotional symptoms of chronic pain. Inhibition of FKBP51, via genetic deletion or pharmacological blockade, in persistent joint pain reduced fast-onset sensory, functional and activity-related symptoms, as well as late anxio-depressive comorbidities. FKBP51 inhibition after the establishment of the hypersensitive state provided only temporary symptoms relief, while acute inhibition at disease onset protected from the full development of sensory and anxio-depressive symptoms for up to 6 months. Our results also indicated that early pain symptoms could predict the late sensory and emotional outcomes of chronic pain. RNA sequencing of spinal cord tissue revealed that late FKBP51 inhibition transiently altered nociceptive genes associated with mechanical hypersensitivity. In contrast, early inhibition persistently downregulated the Naaa gene, a key regulator of the transition to chronic pain, and reorganized spinal cilia. Our results indicate that early FKBP51 inhibition after injury can persistently reduce chronic pain and prevent the onset of associated emotional comorbidities by modulating critical spinal neurobiological pathways that play pivotal roles in the transition to chronic pain. Our study reveals that early inhibition of FKBP51, a modulator in the stress axis, at the onset of joint damage provides sustained pain relief and significantly delays or prevents emotional comorbidities in a sex-dependent manner. In contrast, FKBP51 inhibition initiated after chronic pain is established results in only temporary symptoms improvement. These findings highlight a critical therapeutic window during which timely intervention can prevent the transition from acute to chronic pain. By establishing a predictive link between early therapeutic response and long-term outcomes, this work has important clinical implications for proactive and personalized chronic pain management.

The main advantages of thermal analysis methods are: small sample size (3-10 mg), a wide range of temperature variation programs that can be used, the samples under analysis can be in solid, liquid or gel state and relatively short experimental time. For the sample marked B3, Figure 3 also shows a detail with the variation of the heat flow within the 10 - 70°C range, in order to highlight the existence of the glass transition temperature at 34°C. By analyzing the melting (Tm) and glass transition (Tg) temperatures, one may gather information about the components found in the structure of the materials which the baby teats are made of. According to literature [712], these melting temperature values confirm the presence of polydimethylsiloxane in these samples. For sample B3 made of latex, we see in Figure 3 the existence of two glass transition temperatures Tg1=-60°C and Tg2=34°C. The analysis of literature [7] indicates the presence in this sample of butadiene-styrene rubber (Tg=-59.61°C) and possibly of 2-tert-butylaminoethyl methacrylate (Tg=33°C).

Chronic pain is a hallmark of joint diseases and is often accompanied by negative affective symptoms such as low mood, anxiety and memory dysfunction. Whether these may be the results of the more obvious sensory and functional symptoms of joint pain is poorly understood and this likely contributes to the difficulty in adequately managing this condition. Here, we have used two mouse models to address this lack of knowledge. Using a model of ankle inflammation and a model of knee osteoarthritis, we found that these models of joint pain induced weight bearing deficits of different magnitude but relatively similar mechanical allodynia that lasted at least 3 months. However, the models were accompanied by very different affective outcomes, as only the model of knee osteoarthritis, that led to significant early changes in activity and sleep patterns, was accompanied by an increase in negative affective behaviors, including cognitive impairments and depressive-like behavior. The models also had different molecular profiles at both spinal and hippocampal levels. Importantly, the functional outcomes measured in the early stages of the disease stage strongly correlated with sensory and emotional profiles at 3 months, suggesting that early functional measures may be used as predictors of the long-term symptoms associated with persistent joint pain. In conclusion, the predictive value of early measures of functional impact of joint disease could prove useful in the clinics for adapted therapeutic approaches for the prevention of emotional comorbidities and better pain management for patients with joint pain.Competing Interest StatementThe authors have declared no competing interest.

Every year, the global food industry produces a significant number of wastes and by-products from a variety of sources. By-products from the food-processing sector are produced in large quantities, and because of their undesirable qualities, they are frequently wasted, losing important resources. In order to pursue a circular economy that refers to waste reduction and effective waste management, by-products valorization recently received increased interest. By-products are rich in bioactive compounds and can be used in various industrial applications for health promotion and nutritional benefits. A novel step in its sustainable application is the use of these inexpensive waste agri-food by-products to create the value-added products. The present review intended to summarize the different types of agro-industrial by-products and their properties and highlight their nutritional composition and potential health benefits. Applications of agri-food by-products in foods as well as the potential health and sustainability implications of by-products in food products were also covered. According to research, agri-food by-products can be added to a variety of food to increase their bioactive profile, fiber content, and antioxidant capacity while maintaining good sensory acceptability. Overall, the sustainability of the agri-food chain and consumer health can both benefit from the use of agri-food by-products in food formulation.