Aging is associated with sex-specific alteration in the expression of genes encoding for neuroestradiol synthesis and signaling proteins in the mouse trigeminal somatosensory input.

Pain perception is influenced by sex and aging, with previous studies indicating the involvement of aromatase, the estradiol synthase enzyme, in regulating pain perception. Previous research has established the presence of aromatase in dorsal root ganglia sensory neurons and its role in modulating pain perception. The present study aims to explore the implications of aging and sex on the expression of aromatase and estrogen receptors in the trigeminal ganglion. The study examined mRNA levels of aromatase, ERs, and the androgen receptor (AR) in the trigeminal ganglion of 3-month-old and 27-month-old male and female mice, as well as 3-month-old mice from the four-core genotype (FCG) transgenic model. The latter facilitates the assessment of gonadal hormone and sex chromosome implications for sex-specific traits. Aromatase localization in the ganglion was further assessed through immunohistochemistry. Aromatase immunoreactivity was observed for the first time in sensory neurons within the trigeminal ganglion. Trigeminal ganglion gene expressions were detected for aromatase, ERs, and AR in both sexes. Aromatase, ERß, and GPER gene expressions were higher in young males versus young females. Analyses of the FCG model indicated that sex differences depended solely on gonadal sex. The aging process induced an enhancement in the expression of aromatase, ERs, and AR genes across both sexes, culminating in a reversal of the previously observed gender-based differences. the potential impact of estrogen synthesis and signaling in the trigeminal ganglion on age and sex differences warrants consideration, particularly in relation to trigeminal sensory functions and pain perception.

Ultra-high-precision pneumatic force servo system based on a novel improved particle swarm optimization algorithm integrating Gaussian mutation and fuzzy theory.

In this study, an ultra-high-precision pneumatic force servo system (UPFSS) is proposed. On the one hand, a novel air-floating pneumatic cylinder (AFPC) with an air-floating piston capable of independent air supply and exhaust is developed for this system, and its special flow channel design allows the air-floating piston to be suspended in the cylinder without being constrained by the pressure in the chambers. The friction force of the AFPC is less than 0.0049 N. On the other hand, a leakage chamber is constructed to simulate the clearance between the air-floating piston and the cylinder wall, and a fuzzy proportional integral (FPI)-based pressure control system (PCS) is designed for the simulated leakage chamber. Furthermore, a novel particle swarm optimization algorithm integrating Gaussian mutation and fuzzy theory (IGF-PSO) is presented. After testing, the IGF-PSO algorithm is found to have outstanding optimization performance. Then, the parameters of the FPI controller are optimized through the IGFPSO algorithm. Experimental comparisons reveal that the steady-state error achieved by the parameter-optimized pressure controller in response to the leakage condition is about 38 % smaller than that achieved by the pressure controller with parameters obtained using the trial-and-error method. Finally, the UPFSS is tested by using the optimized PCS to supply compressed air to the chamber of the AFPC. The results show that the UPFSS achieves a steady-state error of no more than 0.0279 N in the continuous step response within the range of 240 N.

Mexican Multicenter Experience of Metastatic Spinal Disease.

Background Spinal metastatic disease is a silent progressive cancer complication with an increasing prevalence worldwide. The spine is the third most common site where solid tumors metastasize. Complications involved in spinal metastasis include root or spinal cord compression, progressing to a declining quality of life as patient autonomy reduces and pain increases. The main objective of this study is to report the incidence of patients and typology of spinal metastases in three reference centers in Mexico. Methodology Retrospective cohorts of patients diagnosed with spinal metastases from January 2010 to February 2017 at the National Cancer Institute, National Rehabilitation Institute, and the Traumatology and Orthopedics Hospital "Lomas Verdes" in Mexico City were analyzed. Results A total of 326 patients (56% males) with spinal metastases were reported. The mean age was 58.06 ± 14.05 years. The main sources of spinal metastases were tumors of unknown origin in 53 (16.25%) cases, breast cancer in 67 (20.5%) cases, prostate cancer in 59 (18%) cases, myeloma in 24 (7.4%) cases, and lung cancer in 23 (7.1%) cases. Conclusions The data obtained in this analysis delivers an updated standpoint on Mexico, providing the opportunity to distinguish the current data from global references. Collecting more epidemiological information for better recording of cancer and its associated complications, as well as further studies on them, is necessary.

Pseudoaneurysm rupture of the splenic artery: a rare cause of gastrointestinal bleeding.

Splenic artery pseudoaneurysm (SAP) is a rare and potentially life-threatening complication of pancreatitis, with a high risk of rupture and mortality rate. Early diagnosis and treatment are crucial, typically through endovascular approaches such as embolization. A 46-year-old woman with chronic pancreatitis experienced gastrointestinal bleeding from a ruptured SAP, which was successfully treated with embolization using hydrocoils, resulting in complete recovery.

Nutritional Strategies for Optimizing Health, Sports Performance, and Recovery for Female Athletes and Other Physically Active Women: A Systematic Review.

CONTEXT: Despite the progress toward gender equality in events like the Olympic Games and other institutionalized competitions, and the rising number of women engaging in physical exercise programs, scientific studies focused on establishing specific nutritional recommendations for female athletes and other physically active women are scarce. OBJECTIVE: This systematic review aimed to compile the scientific evidence available for addressing the question "What dietary strategies, including dietary and supplementation approaches, can improve sports performance, recovery, and health status in female athletes and other physically active women?" DATA SOURCES: The Pubmed, Web of Science, and Scopus databases were searched. DATA EXTRACTION: The review process involved a comprehensive search strategy using keywords connected by Boolean connectors. Data extracted from the selected studies included information on the number of participants and their characteristics related to sport practice, age, and menstrual function. DATA ANALYSIS: A total of 71 studies were included in this review: 17 focused on the analysis of dietary manipulation, and 54 focused on the effects of dietary supplementation. The total sample size was 1654 participants (32.5% categorized as competitive athletes, 30.7% as highly/moderately trained, and 37.2% as physically active/recreational athletes). The risk of bias was considered moderate, mainly for reasons such as a lack of access to the study protocol, insufficient description of how the hormonal phase during the menstrual cycle was controlled for, inadequate dietary control during the intervention, or a lack of blinding of the researchers. CONCLUSION: Diets with high carbohydrate (CHO) content enhance performance in activities that induce muscle glycogen depletion. In addition, pre-exercise meals with a high glycemic index or rich in CHOs increase CHO metabolism. Ingestion of 5-6 protein meals interspersed throughout the day, with each intake exceeding 25 g of protein favors anabolism of muscle proteins. Dietary supplements taken to enhance performance, such as caffeine, nitric oxide precursors, ß-alanine, and certain sport foods supplements (such as CHOs, proteins, or their combination, and micronutrients in cases of nutritional deficiencies), may positively influence sports performance and/or the health status of female athletes and other physically active women. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD480674.

Comparing the Need and Development of Pediatric Palliative Care in Mexico: A Geographical Analysis.

CONTEXT: The Global Atlas of Palliative Care (GAPC) ranked Mexico's palliative care services at a preliminary integration stage into mainstream healthcare services. However, this data does not reflect pediatric palliative care (PPC) development. OBJECTIVES: To analyze the current need and level of development of PPC within Mexico. METHODS: PPC need was estimated using causes of death associated with serious health-related suffering from national mortality data from the General Directorate of Health Information. The level of development was measured through six indicators involving access to PPC services and opioids, then classified using the GAPC development categories adapted to regional territories based on available data. RESULTS: In 2021, 37,444 children died in Mexico. Of those, 10,677 (28.29%) died from conditions with serious health-related suffering, averaging a need for PPC of 25/100,000 children. Out of Mexico's 32 states, two (6.2%) had no PPC activity (category 1), twenty (62.6%) were in a capacity-building phase (category 2), eight (25%) had isolated PPC provision (category 3a), while two (6.2%) had generalized PPC provision (category 3b). No state had early (category 4a) or advanced PPC integration (category 4b). Overall, Mexico was classified as category 2. CONCLUSIONS: PPC services are distributed unevenly across the country, leading to inequitable access to care and an inability to meet the needs of patients and families. There is a disparity between the level of development of adult palliative care services and the underdevelopment of PPC in Mexico. This information can help stakeholders guide the development of PPC where it is needed most.

Ovarian Sex Cord Stromal Tumor in a Free-Ranging Brown Bear (Ursus arctos).

Reports on neoplasms in bears are scarce, especially concerning ovarian tumors. A large primary ovarian neoplasm with multiple metastasis was found during the necropsy of a 14-year-old free-ranging Eurasian brown bear (Ursus arctos) from Northwestern Spain. Histopathology and immunohistochemistry allowed for the diagnosis of a sex cord stromal tumor. This is a complex group of neoplasms which differ in the predominant cell morphology and immunohistochemical features. The microscopic examination revealed two types of cells, one with eosinophilic cytoplasm, intermingled with larger vacuolated cells rich in lipids. The evaluation of the immunoreactivity to different markers, frequently used in the characterization of gonadal tumors (INHA, inhibin-alpha; PLAP, placental alkaline phosphatase; Ki-67; α-SMA, actin alpha-smooth muscle) and inflammation patterns (IBA1, ionized calcium-binding adapter molecule for macrophages; CD3 for T lymphocytes; CD20 for B lymphocytes), displayed significant INHA positive immunostaining of neoplastic cells, as well as inflammatory cell infiltration, mainly composed of macrophages and B lymphocytes. These findings were consistent with a malignant ovarian steroid cell tumor, not otherwise specified. The present study characterizes an unusual type of neoplasm, and also represents the first report of an ovarian sex cord stromal tumor in Ursidae.

Intravascular schwannoma as an extremely unusual cause of vein obstruction: a case report.

The blood vessel lumen is an extremely rare location for a benign peripheral nerve sheath tumor like schwannoma. Less than 10 cases have been previously reported. In this report, we present a case of a 68-year-old woman who had a soft tissue nodule at the posterior calf of her left leg during a physical examination. Pathological examination was performed after complete surgical excision. The patient underwent follow-up for 12 months after surgery without evidence of recurrence or any other complication. This is the first case of intravascular schwannoma reported as a cause of vein obstruction. Microscopically, the tumor was composed of Schwann spindle cells that were immunoreactive for S100 protein and SOX10. This tumor was surrounded by a well-defined vascular smooth muscle wall. Prospective series are required to improve the knowledge on the underlying mechanisms of intravascular schwannoma development.

TaqMan-quantitative PCR assays applied in Neospora caninum knock-outs generated through CRISPR-Cas9 allow to determine the copy numbers of integrated dihydrofolate reductase-thymidylate synthase drug selectable markers.

As for many other organisms, CRISPR-Cas9 mediated genetic modification has gained increasing importance for the identification of vaccine candidates and drug targets in Neospora caninum, an apicomplexan parasite causing abortion in cattle and neuromuscular disease in dogs. A widely used approach for generating knock-out (KO) strains devoid of virulence factors is the integration of a drug selectable marker such as mutated dihydrofolate reductase-thymidylate synthase (mdhfr-ts) into the target gene, thus preventing the synthesis of respective protein and mediating resistance to pyrimethamine. However, CRISPR-Cas9 mutagenesis is not free of off-target effects, which can lead to integration of multiple mdhfr-ts copies into other sites of the genome. To determine the number of integrated mdhfr-ts in N. caninum, a duplex quantitative TaqMan PCR was developed. For this purpose, primers were designed that amplifies a 106 bp fragment from wild-type (WT) parasites corresponding to the single copy wtdhfrs-ts gene, as well as the mutated mdhfrs-ts present in KO parasites that confers resistance and were used simultaneously with primers amplifying the diagnostic NC5 gene. Thus, the dhfr-ts to NC5 ratio should be approximately 1 in WT parasites, while in KO parasites with a single integrated mdhrf-ts gene this ratio is doubled, and in case of multiple integration events even higher. This approach was applied to the Neospora KO strains NcΔGRA7 and NcΔROP40. For NcΔGRA7, the number of tachyzoites determined by dhfr-ts quantification was twice the number of tachyzoites determined by NC5 quantification, thus indicating that only one mdhfr-ts copy was integrated. The results obtained with the NcΔROP40 strain, however, showed that the number of dhfr-ts copies per genome was substantially higher, indicating that at least three copies of the selectable mdhfr-ts marker were integrated into the genomic DNA during gene editing by CRISPR-Cas9. This duplex TaqMan-qPCR provides a reliable and easy-to-use tool for assessing CRISPR-Cas9 mediated mutagenesis in WT N. caninum strains.

Retrospective multicenter study of elderly patients with platinum-sensitive relapsed ovarian cancer treated with trabectedin and pegylated liposomal doxorubicin (pld) in a real-world setting: a geico study.

BACKGROUND: Trabectedin in combination with pegylated liposomal doxorubicin (PLD) is approved for the treatment of patients with platinum-sensitive relapsed ovarian cancer. Nevertheless, there is currently limited information regarding this treatment in elderly patients with ovarian cancer in a real-world setting. METHODS: This observational and multicentric study retrospectively evaluated trabectedin plus PLD in a real-world setting treatment of elderly patients diagnosed with platinum-sensitive relapsed ovarian cancer, treated according to the Summary of Product Characteristics (SmPC) from 15 GEICO-associated hospitals. Patients ≥ 70 years old at the time of treatment initiation and platinum-free intervals ≥ 6 months were considered eligible. RESULTS: Forty-three patients with a median age of 74.0 years were treated between January 1st, 2015, and December 31st, 2019 in 15 Spanish centers. Four patients achieved complete response (9.3%), 14 (32.6%) partial response, and 13 (30.2%) stable disease as the best radiological response. In the analysis of biological overall response according to CA125 serum levels (i.e., Rustin criteria), 14 responded to the treatment (32.6%), 11 responded and normalized (25.6%), three patients stabilized (7.0%) and three progressed (7.0%). Median progression-free survival (PFS) and overall survival (OS) in the study population were 7.7 and 19.5 months, respectively. The most common grade 3/4 adverse events were neutropenia (n = 8, 18.7%) and asthenia (n = 5, 11.6%). CONCLUSIONS: This analysis demonstrated that trabectedin combined with PLD is a feasible and effective treatment in elderly patients with platinum-sensitive relapsed ovarian cancer, showing an acceptable safety profile, which is crucial in the palliative treatment of these patients.

Leptospira spp. and Rickettsia spp. as pathogens with zoonotic potential causing acute undifferentiated febrile illness in a central-eastern region of Peru.

OBJETIVE: this study was to determine the relationship between acute febrile illness and bacterial pathogens with zoonotic potential that cause emerging and re-emerging diseases in a central-eastern region of Peru. RESULTS: Out of the 279 samples analyzed, 23 (8.2%) tested positive for infection by Rickettsia spp., while a total of 15 (5.4%) tested positive for Leptospira spp. Women had a higher frequency of infection by Rickettsia spp., with 13 cases (53.3%), while men had a higher frequency of infection by Leptospira spp., with 10 cases (66.7%). The most frequently reported general symptom was headache, with 100.0% (n = 23) of patients with Rickettsia (+) and 86.7% (n = 13) of patients with Leptospira (+) experiencing it. Arthralgia was the second most frequent symptom, reported by 95.6% (n = 22) and 60% (n = 9) of patients with Rickettsia (+) and Leptospira (+), respectively. Myalgia was reported by 91.3% (n = 21) and 66.7% (n = 10) of patients with Rickettsia (+) and Leptospira (+), respectively. Retroocular pain, low back pain, and skin rash were also present, but less frequently. Among the positives, no manifestation of bleeding was recorded, although only one positive case for Leptospira spp. presented a decrease in the number of platelets.

TIM-3 Expression in Endometriosis.

PROBLEM: Endometriosis is a prevalent chronic gynecological disease linked to immune dysfunction. The protein T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) plays a crucial role in immune system balance. Malfunction of TIM-3 may result in excessive immune activation and inflammatory tissue damage. Given TIM-3's established role in the development of cancer and autoimmune diseases, we decided to study its role in women suffering from endometriosis. STUDY METHOD: We included a total of 62 female patients, all of whom had undergone laparoscopic surgery. Of these, 47 had endometriosis and 15 did not. During surgery, we collected peritoneal fluid (PF) and peripheral blood (PB) samples from every patient for analysis using flow cytometry. To mark the samples, we used a panel of monoclonal antibodies and examined TIM-3 expression in their immune cells. RESULTS: Endometriosis patients in PB demonstrated a significantly lower percentage of CD56+ T cells with TIM-3 expression. As endometriosis progressed through its stages, this expression lessened. This decrease was particularly notable in women with stage III/IV endometriosis. Additionally, both women diagnosed with intestinal endometriosis and those with recent endometriosis diagnoses showed a significantly reduced percentage of CD56+ T cells expressing TIM-3. CONCLUSIONS: Patients with endometriosis exhibit diminished TIM-3 expression within circulating T cells. This warrants further investigation to discern whether it contributes to the progression of endometriosis, potentially through the amplification of autoreactive T cells and inflammation.

Optimising Combat Readiness: Practical Strategies for Integrating Physiological and Psychological Resilience in Soldier Training.

This narrative review examines the intricate psychophysiological interplay between cognitive functions and physical responses within military personnel engaged in combat. It elucidates the spectrum of responses elicited by symmetric and asymmetric warfare alongside specialised combat scenarios, including close-quarters and subterranean warfare. Central to this discourse is the emphasis on integrating training programs beyond physical conditioning to encompass psychological resilience and decision-making efficacy under duress. The exploration further ventures into applying advanced technologies such as virtual reality and wearable devices, highlighting their pivotal role in augmenting training outcomes and supporting soldier health. Through a detailed analysis of psychophysiological variations across different military branches of service, the narrative review advocates for bespoke training regimens and support frameworks tailored to address the unique exigencies of each service branch. Concluding observations stress the importance of evolving military training paradigms, advocating for adopting realistic, immersive training simulations that mirror the complexities of the contemporary battlefield. This synthesis aims to contribute to the ongoing discourse on optimising military training protocols and enhancing the operational readiness and well-being of armed forces personnel. This narrative review is essential for military psychologists, trainers, and policymakers, aiming to bridge the gap between theoretical knowledge and practical implementation in military training programs.

Binary and Ternary Blended Portland Cements Containing Different Types of Rice Husk Ash.

Rice husk ash (RHA) is agricultural waste with high silica content that has exhibited proven technical feasibility as a pozzolanic material since the 1970s. Notwithstanding, its use in mortars and concrete is limited by the standards currently utilized in some countries where RHA production is high and the aforementioned pozzolanic material is not standardized. This is the case in Spain, one of the main rice producers in Europe. Nowadays, the high pressure placed on the Portland cement production sector to reduce its energy use and CO2 emissions has given rise to a keen interest in mineral admixtures for cement manufacturing. In this research, we intended to establish the contributions of different RHA types to the final blended Portland cement properties ("H" is used to identify RHA in standardized cements). The experimental results demonstrated that RHA with good pozzolanic properties (large specific surface and high amorphous silica content) had to be limited to 10% cement replacement because of the severe reduction in workability at higher replacement percentages. RHA with lower reactivity, such as crystalline RHA, or fly ash (FA) can be used to prepare binary and ternary blended cements with reactive RHA. It is possible to design the following cements: CEM II/A-H and CEM II/A-(H-V). It would also be possible to design cement (CEM II/B-(H-V) with replacement values of up to 30% and the same 28-day mechanical performance as observed for the Portland cement without mineral addition.

Dysexecutive symptomatology in everyday functioning and academic achievement in adolescents.

Background: During the educational stage, academic achievement depends on various social, family, and personal factors. Among the latter, executive skills in everyday life play a significant role in dealing with the academic demands of adolescents. Therefore, the aim of this study is to ascertain the effects of executive symptomatology in everyday functioning on academic achievement in adolescents. Method: The study involved 910 students aged between 13 and 15 years (M = 14.09, SD = 0.68) from both public and private schools in the Community of Madrid. The DEX, BDEFS-CA, and BRIEF-SR questionnaires were utilised to assess executive difficulties, while grades in language, mathematics, and natural sciences were used as a measure of academic achievement. Results: The data revealed statistically significant differences in working memory, emotional control, materials organisation, and task completion. In relation to language and natural sciences subjects. In the case of mathematics, emotional control and task completion were significant variables. Conclusion: Our results indicate that certain executive skills that are manifested in everyday life activities can contribute, albeit in a variable way, to academic achievement in the subjects studied. This aspect is relevant insofar as it allows us to develop preventive interventions based on the executive training of these everyday skills.

Advancements in Artificial Intelligence for Precision Diagnosis and Treatment of Myocardial Infarction: A Comprehensive Review of Clinical Trials and Randomized Controlled Trials.

Coronary artery disease (CAD) is still a serious global health issue that has a substantial impact on death and illness rates. The goal of primary prevention strategies is to lower the risk of developing CAD. Nevertheless, current methods usually rely on simple risk assessment instruments that might overlook significant individual risk factors. This limitation highlights the need for innovative methods that can accurately assess cardiovascular risk and offer personalized preventive care. Recent advances in machine learning and artificial intelligence (AI) have opened up interesting new avenues for optimizing primary preventive efforts for CAD and improving risk prediction models. By leveraging large-scale databases and advanced computational techniques, AI has the potential to fundamentally alter how cardiovascular risk is evaluated and managed. This review looks at current randomized controlled studies and clinical trials that explore the application of AI and machine learning to improve primary preventive measures for CAD. The emphasis is on their ability to recognize and include a range of risk elements in sophisticated risk assessment models.

Fabrication and histological evaluation of a self-setting granular cement using calcium sulfate hemihydrate granules with different pore distribution.

Granular type of bone substitutes is currently used in the field of dentistry to restore alveolar bone defects. However, the migration of the granules from the implantation site is still an unresolved issue. In this study, the feasibility to fabricate self-setting calcium sulfate hemihydrate (CSH) granules using different ranges of loading pressure: CSH(0), CSH(50), CSH(100), and CSH(150) was investigated with the hypothesis that CSH granules with reduced microporosity can inhibit the rapid dissolution rate of the calcium sulfate dihydrate (CSD) set blocks and induce bone regeneration. After 4 weeks of implantation, the granules were mostly replaced with new bone although no significant differences were observed. Nevertheless, the granules demonstrated the ability to set within the bone defect. It is therefore concluded that the setting ability of calcium sulfate can contribute to address the issue of migration of the granules and provide a useful guide for designing setting bone substitutes.

Implications of human-wildlife conflict on the diet of an endangered avian top predator in the northern Andes.

Conflicts between rural people and the Endangered Black-and-chestnut Eagle (Spizaetus isidori) are a prominent conservation concern in the northern Andes, as at least 60 eagles were poached between 2000 and 2022 in response to poultry predation. Here, we conducted direct observations to analyze the Black-and-chestnut Eagle diet and evaluated how forest cover affects the feeding habits of the species during nestling-rearing periods in 16 nests located in different human-transformed Andean landscapes of Ecuador and Colombia. We analyzed 853 prey items (46 species) delivered to nestlings. We used Generalized Linear Models to test whether the percent forest cover calculated within varying buffer distances around each nest and linear distances from the nest to the nearest settlement and pasture areas were predictors of diet diversity and biomass contribution of prey. Forest cover was not a factor that affected the consumption of poultry; however, the eagle regularly preyed on chickens (Gallus gallus) (i.e., domestic Galliformes) which were consumed by 15 of the 16 eagle pairs, with biomass contributions (14.57% ± 10.55) representing 0.6-37% of the total prey consumed. The Black-and-chestnut Eagle is an adaptable generalist able to switch from mammalian carnivores to guans (i.e., wild Galliformes) in human-dominated landscapes, and eagles nesting in sites with low forest cover had a less diverse diet than those in areas with more intact forests. Management actions for the conservation of this avian top predator require studies on the eagle's diet in areas where human persecution is suspected or documented, but also maintaining forest cover for the wild prey of the species, development of socio-economic and psychological assessments on the drivers behind human-eagle conflicts, and the strengthening of technical capacities of rural communities, such as appropriate poultry management.

How effective is proximal fibular osteotomy in redistributing joint pressures? Insights from an HTO comparative in-silico study.

BACKGROUND: Knee osteoarthritis (KOA) represents a widespread degenerative condition among adults that significantly affects quality of life. This study aims to elucidate the biomechanical implications of proximal fibular osteotomy (PFO), a proposed cost-effective and straightforward intervention for KOA, comparing its effects against traditional high tibial osteotomy (HTO) through in-silico analysis. METHODS: Using medical imaging and finite element analysis (FEA), this research quantitatively evaluates the biomechanical outcomes of a simulated PFO procedure in patients with severe medial compartment genu-varum, who have undergone surgical correction with HTO. The study focused on evaluating changes in knee joint contact pressures, stress distribution, and anatomical positioning of the center of pressure (CoP). Three models are generated for each of the five patients investigated in this study, a preoperative original condition model, an in-silico PFO based on the same original condition data, and a reversed-engineered HTO in-silico model. RESULTS: The novel contribution of this investigation is the quantitative analysis of the impact of PFO on the biomechanics of the knee joint. The results provide mechanical evidence that PFO can effectively redistribute and homogenize joint stresses, while also repositioning the CoP towards the center of the knee, similar to what is observed post HTO. The findings propose PFO as a potentially viable and simpler alternative to conventional surgical methods for managing severe KOA, specifically in patients with medial compartment genu-varum. CONCLUSION: This research also marks the first application of FEA that may support one of the underlying biomechanical theories of PFO, providing a foundation for future clinical and in-silico studies.

Understanding the coupling of non-metallic heteroatoms to CO2 from a Conceptual DFT perspective.

CONTEXT: A Conceptual DFT (CDFT) study has been carry out to analyse the coupling reactions of the simplest amine (CH3NH2), alcohol (CH3OH), and thiol (CH3SH) compounds with CO2 to form the corresponding adducts CH3NHCO2H, CH3OCO2H, and CH3SCO2H. The reaction mechanism takes place in a single step comprising two chemical events: nucleophilic attack of the non-metallic heteroatoms to CO2 followed by hydrogen atom transfer (HAT). According to our calculations, the participation of an additional nucleophilic molecule as HAT assistant entails important decreases in activation electronic energies. In such cases, the formation of a six-membered ring in the transition state (TS) reduces the angular stress with respect to the non-assisted paths, characterised by four-membered ring TSs. Through the analysis of the energy and reaction force profiles along the intrinsic reaction coordinate (IRC), the ratio of structural reorganisation and electronic rearrangement for both activation and relaxation energies has been computed. In addition, the analysis of the electronic chemical potential and reaction electronic flux profiles confirms that the highest electronic activity as well as their changes take place in the TS region. Finally, the distortion/interaction model using an energy decomposition scheme based on the electron density along the reaction coordinate has been carried out and the relative energy gradient (REG) method has been applied to identify the most important components associated to the barriers. METHODS: The theoretical calculation were performed with Gaussian-16 scientific program. The B3LYP-D3(BJ)/aug-cc-pVDZ level was used for optimization of the minima and TSs. IRC calculations has also been carried out connecting the TS with the associated minima. Conceptual-DFT (CDFT) calculations have been carried out with the Eyringpy program and in-house code. The distortion/interaction model along the reaction coordinate have used the decomposition scheme of Mandado et al. and the analysis of the importance of each components have been done with the relative energy gradient (REG) method.