Small non-coding RNAs and pancreatic ductal adenocarcinoma: Linking diagnosis, pathogenesis, drug resistance, and therapeutic potential.

This review comprehensively investigates the intricate interplay between small non-coding RNAs (sncRNAs) and pancreatic ductal adenocarcinoma (PDAC), a devastating malignancy with limited therapeutic options. Our analysis reveals the pivotal roles of sncRNAs in various facets of PDAC biology, spanning diagnosis, pathogenesis, drug resistance, and therapeutic strategies. sncRNAs have emerged as promising biomarkers for PDAC, demonstrating distinct expression profiles in diseased tissues. sncRNA differential expression patterns, often detectable in bodily fluids, hold potential for early and minimally invasive diagnostic approaches. Furthermore, sncRNAs exhibit intricate involvement in PDAC pathogenesis, regulating critical cellular processes such as proliferation, apoptosis, and metastasis. Additionally, mechanistic insights into sncRNA-mediated pathogenic pathways illuminate novel therapeutic targets and interventions. A significant focus of this review is dedicated to unraveling sncRNA mechanisms underlying drug resistance in PDAC. Understanding these mechanisms at the molecular level is imperative for devising strategies to overcome drug resistance. Exploring the therapeutic landscape, we discuss the potential of sncRNAs as therapeutic agents themselves as their ability to modulate gene expression with high specificity renders them attractive candidates for targeted therapy. In summary, this review integrates current knowledge on sncRNAs in PDAC, offering a holistic perspective on their diagnostic, pathogenic, and therapeutic relevance. By elucidating the roles of sncRNAs in PDAC biology, this review provides valuable insights for the development of novel diagnostic tools and targeted therapeutic approaches, crucial for improving the prognosis of PDAC patients.

Laparoscopic Conversion to Open Cholecystectomy: Is Incidental Gallbladder Cancer Any Different?

BACKGROUND: A majority of gallbladder cancers present incidentally. Operative risk factors and outcomes for laparoscopic converted to open cholecystectomy in incidental gallbladder cancer are not well characterized. METHODS: Patients with incidental gallbladder cancer and acute cholecystitis undergoing laparoscopic cholecystectomy and conversion to open cholecystectomy in the National Surgical Quality Improvement Program (NSQIP) database of the American College of Surgeons (ACS) from 2010-2019 were reviewed. The primary endpoint was risk factors for conversion to open cholecystectomy in incidental gallbladder cancer. Chi-squared test or Fisher's exact test was used for categorical variables. Continuous variables were compared using the Mann-Whitney U test. RESULTS: A total of 5,789 patients undergoing laparoscopic cholecystectomy were identified, of which, 50 (0.9%) had incidental gallbladder cancer. For incidental gallbladder cancer patients, there were no differences in preoperative profile and risk factors between laparoscopic and converted to open cholecystectomy groups. Incidental carcinoma patients undergoing conversion to open cholecystectomy had lower preoperative sodium levels than the laparoscopic cholecystectomy group (P=0.007). Hospital length of stay (days) was longer for those with a conversion to open cholecystectomy for incidental carcinoma compared to non-conversion, 14 (10.8, 18.8) vs 2 (0.3, 5) (P=0.004). The patients converted to open cholecystectomy also had higher rates of postoperative sepsis (50% vs 0%, P<0.001) and reoperation than the laparoscopic cohort (50% vs 2.2%, P<0.001). Readmission and mortality rates, among other complications, were not significantly different between both surgical approaches in incidental gallbladder cancer patients. CONCLUSIONS:  Patients with conversion to open cholecystectomy had worse outcomes including longer hospital stays and higher rates of sepsis and reoperation. It remains difficult to predict which incidental gallbladder patients will require a conversion to open surgery. Further study examining whether more complicated recovery results in worse oncologic outcomes is warranted.

Oxysterol-binding protein like 7 deficiency leads to ER stress mediated apoptosis in podocytes and proteinuria.

Chronic kidney disease (CKD) is associated with renal lipid dysmetabolism among a variety of other pathways. We recently demonstrated that oxysterol-binding protein like 7 (OSBPL7) modulates the expression and function of ATP Binding Cassette Subfamily A Member 1 (ABCA1) in podocytes, a specialized type of cell essential for kidney filtration. Drugs that target OSBPL7 lead to improved renal outcomes in several experimental models of CKD. However, the role of OSBPL7 in podocyte injury remains unclear. Employing mouse models and cellular assays, we investigated the influence of OSBPL7 deficiency on podocytes. We demonstrated that reduced renal OSBPL7 levels as observed in two different models of experimental CKD are linked to increased podocyte apoptosis, primarily mediated by heightened endoplasmic reticulum (ER) stress. While as expected the absence of OSBPL7 also resulted in lipid dysregulation (increased lipid droplets and triglycerides content), OSBPL7-deficiency related lipid dysmetabolism did not contribute to podocyte injury. Similarly, we demonstrated that the decreased autophagic flux we observed in OSBPL7-deficient podocytes was not the mechanistic link between OSBPL7-deficiency and apoptosis. In a complementary zebrafish model, osbpl7 knockdown was sufficient to induce proteinuria and morphological damage to the glomerulus, underscoring its physiological relevance. Our study shed new light on the mechanistic link between OSBPL7 deficiency and podocyte injury in glomerular diseases associated with CKD, and it strengthen the role of OSBPL7 as a novel therapeutic target.

Revealing the role of material properties in impact-related injuries: Investigating the influence of brain and skull density variations on head injury severity.

Traumatic brain injuries (TBI) resulting from head impacts are a major public health concern, which prompted our research to investigate the complex relationship between the material properties of brain tissue and the severity of TBI. The goal of this research is to investigate how variations in brain and skull density influence the vulnerability of brain tissue to traumatic injury, thereby enhancing our understanding of injury mechanism. To achieve this goal, we employed a well-validated finite element head model (FEHM). The current investigation was divided into two phases: in the first one, three distinct brain viscoelastic materials that had been utilized in prior studies were analyzed. The review of the properties of these three materials has been meticulous, encompassing both the spectrum of mechanical properties and the behaviors that are relevant to the way in which brain tissue reacts to traumatic loading conditions. In the second phase, the material properties of both the brain and skull tissue, alongside the impact conditions, were held constant. After this step, the focus was directed towards the variation of density in the brain and skull, which was consistent with the results obtained from previous experimental investigations, in order to determine the precise impact of these variations in density. This approach allowed a more profound comprehension of the impacts that density had on the simulation results. In the first phase, Material No. 2 exhibited the highest maximum first principal strain value in the frontal region (εmax=15.41%), indicating lower stiffness to instantaneous deformation. This characteristic suggests that Material No. 2 may deform more extensively upon impact, potentially increasing the risk of injury due to its viscoelastic behavior. In contrast, Material No. 1, with a lower maximum first principal strain in the frontal region (εmax=7.87%), displayed greater stiffness to instantaneous deformation, potentially reducing the risk of brain injury upon head impact. The second phase provided quantitative findings revealing a proportional relationship between brain tissue density and the pressures experienced by the brain. A 2 % increase in brain tissue density corresponded to approximately a 1 % increase in pressure on the brain tissue. Similarly, changes in skull density exhibited a similar quantitative relationship, with a 6 % increase in skull density leading to a 2.5 % increase in brain pressure. This preliminary approximate ratio of 2 to 1 between brain and skull density variations provides an initial quantitative framework for assessing the impact of density changes on brain vulnerability. These findings have several implications for the development of protective measures and injury prevention strategies, particularly in contexts where head trauma is a major issue.

Privilege and distress intolerance at the margins: Exploring the role of critical consciousness and entitlement.

With a U.S.-based sample of 219 people of color with diverse sexual orientations, the present study aimed to reveal how perceived privilege may be associated with distress intolerance, and the mediating roles of critical consciousness and entitlement. Data were also used to explore the interaction of sexual orientation status (heterosexual or sexual minority) with these paths. Via path analysis, we found that privilege was unrelated to critical consciousness, yielded a positive direct link to entitlement, and had a negative direct link to distress intolerance. Tests of indirect relations showed that privilege had a significant indirect relation to distress intolerance via entitlement but not critical consciousness. Regarding moderation analyses, the Privilege × Sexual Minority Status interaction predicting entitlement, privilege was significantly positively associated with entitlement among both heterosexual and sexual minority participants, but the association was significantly stronger for heterosexual participants. For the Critical Consciousness × Sexual Minority Status interaction predicting distress intolerance, the association of critical consciousness with distress intolerance was nonsignificant for both heterosexual and sexual minority participants, but the association changed direction and was significantly stronger for sexual minority participants. Indirect relations did not differ for sexual minority or heterosexual participants. Implications for future research and intervention are addressed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Amplifying Curcumin's Antitumor Potential: A Heat-Driven Approach for Colorectal Cancer Treatment.

Introduction: Peritoneal metastases from colorectal cancer (CRC) present a significant clinical challenge with poor prognosis, often unresponsive to systemic chemotherapy. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment approach for select patients. The use of curcumin, a natural compound with antitumor properties, in HIPEC is of interest due to its lower side effects compared to conventional drugs and potential for increased efficacy through direct delivery to the peritoneal cavity. Methods: An in vitro hyperthermic model was developed to simulate clinical HIPEC conditions. Three colon cancer cell lines (SK-CO-1, COLO205, SNU-C1) representing different genetic mutations (p53, KRAS, BRAF) were treated with either curcumin (25 µM) or mitomycin-C (1 µM) for 1, 2, or 3 hours. Post-treatment, cells were incubated at 37°C (normothermia) or 42°C (hyperthermia). Cell viability and proliferation were assessed at 24, 48 and 72 hours post-treatment using Annexin V/PI, MTT assay, trypan blue exclusion, and Hoffman microscopy. Results: Hyperthermia significantly enhanced the antitumor efficacy of curcumin, evidenced by a two-fold reduction in cell viability compared to normothermia across all cell lines. In the SNU-C1 cell line, which harbors a p53 mutation, mitomycin-C failed to significantly impact cell viability, unlike curcumin, suggesting mutation-specific differences in treatment response. Discussion: The findings indicate that hyperthermia augments the antitumor effects of curcumin in vitro, supporting the hypothesis that curcumin could be a more effective HIPEC agent than traditional drugs like mitomycin-C. Mutation-associated differences in response to treatments were observed, particularly in p53 mutant cells. While further studies are needed, these preliminary results suggest that curcumin in HIPEC could represent a novel therapeutic strategy for CRC patients with peritoneal metastases. This approach may offer improved outcomes with fewer side effects, particularly in genetically distinct CRC subtypes.

Adjuvant Radiotherapy for Surgically Resected Stage III Merkel Cell Carcinoma.

This case-control study evaluates whether adjuvant radiotherapy is associated with overall survival among patients with surgically resected stage III Merkel cell carcinoma.

Quantifying the effect of cerebral atrophy on head injury risk in elderly individuals: Insights from computational biomechanics and experimental analysis of bridging veins.

The objective of this study was to quantitatively investigate the relationship between cerebral atrophy and the risk of injury in elderly individuals. To achieve this, a sophisticated computational biomechanics approach utilizing finite element analysis was employed to simulate the mechanical behavior of the brain and skull under various conditions. In addition, particular emphasis was placed on understanding the role of cerebral bridging veins (BVs) and their mechanical properties at different ages in the occurrence of head injuries. Head models representing healthy brains and five atrophy models were developed based on imaging data. After validation, the models underwent the identical impact loading conditions to enable the simulation of brain damage. The resulting outcomes of the models with brain atrophy were then compared to the results obtained from the healthy model, allowing for a comparative analysis. Simulations showed increased relative displacement with worsening brain atrophy, particularly in the frontal and occipital regions. Compared to the healthy brain model, relative displacement increased by 2.36 %-9.21 % in the atrophy models, indicating an elevated risk of injury. In severe brain atrophy (FEM 6), the strain reached 83.59 % in local model simulations, leading to damage and rupture of cerebral BVs in both young and elderly individuals. Mechanical tests on cerebral BVs demonstrated a negative correlation between age and ultimate force, stress, and strain, suggesting increased susceptibility to damage with age. An observed sharp decline of approximately 50 % in ultimate stress and 35 % in ultimate strain was noted as age increased. We implemented a 50 % reduction in the intensity of head impact forces; nevertheless, vascular damage continues to manifest in the elderly population. To establish a truly safe zone, it is imperative to further decrease the intensity of the impact. This investigation represents a significant step forward in our understanding of the complex interplay between cerebral atrophy, the mechanical properties of BVs at different age, and the risk of head injury in the elderly. Through continued research in this field, we can strive to improve the quality of care, enhance prevention strategies, and ultimately enhance the well-being and safety of the elderly population.

Delayed surgery and health related quality of life in patients with proximal femoral fracture.

This study aimed to establish factors associated with delayed surgery in patients with proximal femoral fracture and to assess patients' health-related quality of life (HRQoL) after surgery including all-cause 6-months mortality. This was a single-center, observational, prospective cohort study that included patients with a proximal femur fracture. We described patients' HRQoL measured by EuroQoL (EQ-5D-5L and EQ-VAS) questionnaire and perioperative complications (including mortality) 6 months after surgery. We included 163 patients with a mean age of 80.5 years, the majority were women and 76.1% reported falling from their own height. The mean time between hospital admission and surgery was 8.3 days (SD 4.9 days) and the mean hospital stay was 13.5 days (SD 10.4 days). After adjustment, the principal factor associated with delayed surgery was adjournment in surgery authorization (3.7 days). EQ-5D-5L index values and the VAS score at 1 month after surgery were 0.489 and 61.1, at 3 months were 0.613 and 65.8, and at 6 months 0.662 and 66.7 respectively. Mortality at 6 months of follow-up was 11% (18 patients). In conclusion, administrative authorization was the strongest associated factor with delayed time from hospital admission to surgery. HRQoL of patients with a proximal femoral fracture improved 6 months after surgery.Trial registration: NCT04217642.

Timeliness of Multimodal Care for At-Risk Breast Cancer Patients at a Safety Net Institution.

INTRODUCTION: Because limited data exist, we sought to evaluate timeliness of multimodal treatments in a safety net breast cancer population. METHODS: Breast cancer patients treated at a safety net hospital from 2016 to 2020 were analyzed retrospectively. Time intervals were defined as primary time (PT) from diagnosis to initiation of primary intervention, secondary time (ST) from completion of primary to initiation of secondary intervention, and tertiary time (TT) from completion of secondary to initiation of tertiary intervention. Variables included primary language, insurance type, and race. RESULTS: Of 223 patients, 99 (44.4%) primarily spoke Spanish, 29 (13.0%) were of Black race, and 184 (82.5%) had Medicaid or uninsured status. Median (IQR) age at diagnosis was 55 (48-62) years. Primary intervention was surgical in 127/216 (58.8%); secondary intervention was systemic in 38/169 (22.5%); and tertiary intervention was radiation in 67/80 (83.8%). Overall, median days (IQR) for PT were 69 (53, 98), ST were 65 (42, 95), and TT were 69 (43, 88). PT was significantly longer in Black [105 (76, 142) days] patients compared to non-Hispanic White patients [68 (51, 107) days, P = 0.031)] and White Hispanic patients [65 (53,91) days, P = 0.014]. There were no significant differences in PT, ST, or TT by spoken language or insurance type. CONCLUSIONS: Black patients remain at risk due to prolonged time to intervention. Spanish-speaking status was not associated with inferior timeliness or completion of multimodal care at a safety net hospital. Identifying safety net hospital barriers to achieving benchmarks for timely completion of all phases of multimodal care warrants further attention.

Impact of the 2021 La Palma volcanic eruption on air quality: Insights from a multidisciplinary approach.

The La Palma 2021 volcanic eruption was the first subaerial eruption in a 50-year period in the Canary Islands (Spain), emitting ~1.8 Tg of sulphur dioxide (SO2) into the troposphere over nearly 3 months (19 September-13 December 2021), exceeding the total anthropogenic SO2 emitted from the 27 European Union countries in 2019. We conducted a comprehensive evaluation of the impact of the 2021 volcanic eruption on air quality (SO2, PM10 and PM2.5 concentrations) utilising a multidisciplinary approach, combining ground and satellite-based measurements with height-resolved aerosol and meteorological information. High concentrations of SO2, PM10 and PM2.5 were observed in La Palma (hourly mean SO2 up to ~2600 µg m-3 and also sporadically at ~140 km distance on the island of Tenerife (> 7700 µg m-3) in the free troposphere. PM10 and PM2.5 daily mean concentrations in La Palma peaked at ~380 and 60 µg m-3. Volcanic aerosols and desert dust both impacted the lower troposphere in a similar height range (~ 0-6 km) during the eruption, providing a unique opportunity to study the combined effect of both natural phenomena. The impact of the 2021 volcanic eruption on SO2 and PM concentrations was strongly influenced by the magnitude of the volcanic emissions, the injection height, the vertical stratification of the atmosphere and its seasonal dynamics. Mean daily SO2 concentrations increased during the eruption, from 38 µg m-3 (Phase I) to 92 µg m-3 (Phase II), showing an opposite temporal trend to mean daily SO2 emissions, which decreased from 34 kt (Phase I) to 7 kt (Phase II). The results of this study are relevant for emergency preparedness in all international areas at risk of volcanic eruptions; a multidisciplinary approach is key to understand the processes by which volcanic eruptions affect air quality and to mitigate and minimise impacts on the population.

Adsorption of acrolein and its hydrogenation products on Cu(111).

The adsorption of acrolein and its hydrogenation products propanal, 1-propanol, and 2-propenol on Cu(111) was studied by reflection absorption infrared spectroscopy (RAIRS) and temperature-programmed desorption (TPD). The experimental RAIR spectra were obtained by adsorbing multilayers of each molecule at 85 K and then annealing the surface up to 200 K to desorb the multilayer and produce the most stable monolayer structure on the surface. Each of the four molecules adsorbs weakly to the surface and desorbs at temperatures below 225 K. Compared to acrolein and propanal, the two alcohols, 2-propenol and 1-propanol, have notably higher desorption temperatures and broadened and redshifted O-H stretches that reveal strong hydrogen bonding in the multilayers. Upon annealing to 160 K, the OH stretches of both 2-propenol and 1-propanol disappear, indicating the hydrogen bonding in the multilayers is not present in the monolayers. For 2-propenol, the hydrogen bonding in the multilayer correlates with the observation of the CC stretch at 1647 cm-1, which is invisible for the monolayer. This suggests that the CC bond is parallel to the surface for monolayer coverages of 2-propenol. Similarly, for propanal, the CO stretch peak at 1735 cm-1 compared to those at 1671 and 1695 cm-1 is very weak at low coverages but becomes the most prominent peak for the multilayer, indicating a change in molecular orientation. For acrolein, the out-of-plane bending modes are more intense than the CO stretch at submonolayer coverages, indicating that the molecular plane is mainly parallel to the surface. In contrast, the opposite intensity trend was observed for multilayer acrolein, suggesting that the CO bonds are tilted away from the surface.

Activation of Stimulator of IFN Genes (STING) Causes Proteinuria and Contributes to Glomerular Diseases.

BACKGROUND: The signaling molecule stimulator of IFN genes (STING) was identified as a crucial regulator of the DNA-sensing cyclic GMP-AMP synthase (cGAS)-STING pathway, and this signaling pathway regulates inflammation and energy homeostasis under conditions of obesity, kidney fibrosis, and AKI. However, the role of STING in causing CKD, including diabetic kidney disease (DKD) and Alport syndrome, is unknown. METHODS: To investigate whether STING activation contributes to the development and progression of glomerular diseases such as DKD and Alport syndrome, immortalized human and murine podocytes were differentiated for 14 days and treated with a STING-specific agonist. We used diabetic db/db mice, mice with experimental Alport syndrome, C57BL/6 mice, and STING knockout mice to assess the role of the STING signaling pathway in kidney failure. RESULTS: In vitro, murine and human podocytes express all of the components of the cGAS-STING pathway. In vivo, activation of STING renders C57BL/6 mice susceptible to albuminuria and podocyte loss. STING is activated at baseline in mice with experimental DKD and Alport syndrome. STING activation occurs in the glomerular but not the tubulointerstitial compartment in association with autophagic podocyte death in Alport syndrome mice and with apoptotic podocyte death in DKD mouse models. Genetic or pharmacologic inhibition of STING protects from progression of kidney disease in mice with DKD and Alport syndrome and increases lifespan in Alport syndrome mice. CONCLUSION: The activation of the STING pathway acts as a mediator of disease progression in DKD and Alport syndrome. Targeting STING may offer a therapeutic option to treat glomerular diseases of metabolic and nonmetabolic origin or prevent their development, progression, or both.

Spanish-Speaking Status: A Protective Factor in Colorectal Cancer Presentation at a Safety-Net Hospital.

INTRODUCTION: Lower screening rates and poorer outcomes for colorectal cancer have been associated with Hispanic ethnicity and Spanish-speaking status, respectively. METHODS: We reviewed sequential colorectal cancer patients evaluated by the surgical service at a safety-net hospital (SNH) (2016-2019). Insurance type, stage, cancer type, surgery class (elective/urgent), initial surgeon contact setting (outpatient clinic/inpatient consult), operation (resection/diversion), and follow-up were compared by patient-reported primary spoken language. RESULTS: Of 157 patients, 85 (54.1%) were men, 91 (58.0%) had colon cancer, 67 (42.7%) primarily spoke Spanish, and late stage (III or IV) presentations occurred in 83 (52.9%) patients. The median age was 58 y, cancer resection was completed in 48 (30.6%) patients, and 51 (32.5%) patients were initially seen as inpatient consults. On univariate analysis, Spanish-speaking status was significantly associated with female sex, Medicaid insurance, being seen as an outpatient consult, and undergoing elective and resection surgery. On multivariable logistic regression, Spanish-speaking patients had higher odds of having Medicaid insurance (AOR 2.28, P = 0.019), receiving a resection (AOR 3.96, P = 0.006), and undergoing an elective surgery (AOR 3.24, P = 0.025). Spanish-speaking patients also had lower odds of undergoing an initial inpatient consult (AOR 0.34, P = 0.046). CONCLUSIONS: Spanish-speaking status was associated with a lower likelihood of emergent presentation and need for palliative surgery among SNH colorectal cancer patients. Further research is needed to determine if culturally competent infrastructure in the SNH setting translates into Spanish-speaking status as a potentially protective factor.

Novel Treatments for Age-Related Macular Degeneration: A Review of Clinical Advances in Sustained Drug Delivery Systems.

In recent years, the number of patients with ocular diseases is increasing as a consequence of population aging. Among them, one of the most common is the age-related macular degeneration (AMD), a condition that leads to vision loss if it is not treated. AMD is a multifactorial disorder with two advanced forms, dry and neovascular AMD. Currently, although there is no approved therapy that significantly impacts dry AMD progression, several pharmacologic therapies exist for neovascular AMD. Notwithstanding, evidence suggests a suboptimal result in a high number of patients receiving these therapeutic options. Consequently, finding effective strategies is not only a still unmet medical need in dry AMD but also in neovascular AMD. This underlines the need for new drug delivery technologies that can improve the pharmacological action and drug concentration at the target sites. In this regard, sustained drug delivery systems are presented as the most promising therapeutic options in AMD patients. This review summarized the pathogenesis and the current treatment options for AMD, focusing on the emerging ocular sustained drug delivery approaches undergoing clinical trials.

Viscoelastic Characterization of a Thermoplastic Elastomer Processed through Material Extrusion.

Objective. We aim to characterize the viscoelastic behavior of Polyether-Block-Amide (PEBA 90A), provide reference values for the parameters of a constitutive model for the simulation of mechanical behaviors, and paying attention to the influence of the manufacturing conditions. Methods. Uniaxial relaxation tests of filaments of PEBA were used to determine the values of the parameters of a Prony series for a Quasi-Linear Visco-Elastic (QLVE) model. Additional, fast cyclic loading tests were used to corroborate the adequacy of the model under different test criteria in a second test situation. Results. The QLVE model predicts the results of the relaxation tests very accurately. In addition, the behavior inferred from this model fits very well with the measurements of fast cyclic loading tests. The viscoelastic behavior of PEBA under small strain polymer fits very well to a six-parameter QLVE model.

Self-Sorting Governed by Chelate Cooperativity.

Self-sorting phenomena are the basis of manifold relevant (bio)chemical processes where a set of molecules is able to interact with no interference from other sets and are ruled by a number of codes that are programmed in molecular structures. In this work, we study, the relevance of chelate cooperativity as a code for achieving high self-sorting fidelities. In particular, we establish qualitative and quantitative relationships between the cooperativity of a cyclic system and the self-sorting fidelity when combined with other molecules that share identical geometry and/or binding interactions. We demonstrate that only systems displaying sufficiently strong chelate cooperativity can achieve quantitative narcissistic self-sorting fidelities either by dictating the distribution of cyclic species in complex mixtures or by ruling the competition between the intra- and intermolecular versions of a noncovalent interaction.

Injury Metrics for Assessing the Risk of Acute Subdural Hematoma in Traumatic Events.

Worldwide, the ocurrence of acute subdural hematomas (ASDHs) in road traffic crashes is a major public health problem. ASDHs are usually produced by loss of structural integrity of one of the cerebral bridging veins (CBVs) linking the parasagittal sinus to the brain. Therefore, to assess the risk of ASDH it is important to know the mechanical conditions to which the CBVs are subjected during a potentially traumatic event (such as a traffic accident or a fall from height). Recently, new studies on CBVs have been published allowing much more accurate prediction of the likelihood of mechanical failure of CBVs. These new data can be used to propose new damage metrics, which make more accurate predictions about the probability of occurrence of ASDH in road crashes. This would allow a better assessement of the effects of passive safety countermeasures and, consequently, to improve vehicle restraint systems. Currently, some widely used damage metrics are based on partially obsolete data and measurements of the mechanical behavior of CBVs that have not been confirmed by subsequent studies. This paper proposes a revision of some existing metrics and constructs a new metric based on more accurate recent data on the mechanical failure of human CBVs.

Viscoelastic Characterization of Parasagittal Bridging Veins and Implications for Traumatic Brain Injury: A Pilot Study.

Many previous studies on the mechanical properties of Parasagittal Bridging Veins (PSBVs) found that strain rate had a significant effect on some mechanical properties, but did not extensively study the viscoelastic effects, which are difficult to detect with uniaxial simple tensile tests. In this study, relaxation tests and tests under cyclic loading were performed, and it was found that PSBVs do indeed exhibit clear viscoelastic effects. In addition, a complete viscoelastic model for the PSBVs is proposed and data from relaxation, cyclic load and load-unload tests for triangular loads are used to find reference values that characterize the viscoelastic behavior of the PSBVs. Although such models have been proposed for other types of blood vessels, this is the first study that clearly demonstrates the existence of viscoelastic effects from an experimental point of view and also proposes a specific model to explain the data obtained. Finally, this study provides reference values for the usual viscoelastic properties, which would allow more accurate numerical simulation of PSBVs by means of computational models.

Mechanical Behavior of Blood Vessels: Elastic and Viscoelastic Contributions.

The mechanical properties of the cerebral bridging veins (CBVs) were studied using advanced microtensile equipment. Detailed high-quality curves were obtained at different strain rates, showing a clearly nonlinear stress-strain response. In addition, the tissue of the CBVs exhibits stress relaxation and a preconditioning effect under cyclic loading, unequivocal indications of viscoelastic behavior. Interestingly, most previous literature that conducts uniaxial tensile tests had not found significant viscoelastic effects in CBVs, but the use of more sensitive tests allowed to observe the viscoelastic effects. For that reason, a careful mathematical analysis is presented, clarifying why in uniaxial tests with moderate strain rates, it is difficult to observe any viscoelastic effect. The analysis provides a theoretical explanation as to why many recent studies that investigated mechanical properties did not find a significant viscoelastic effect, even though in other circumstances, the CBV tissue would clearly exhibit viscoelastic behavior. Finally, this study provides reference values for the usual mechanical properties, as well as calculations of constitutive parameters for nonlinear elastic and viscoelastic models that would allow more accurate numerical simulation of CBVs in Finite Element-based computational models in future works.