Right-sided ligamentum teres (RSLT) is a rare anatomic variant in which the fetal umbilical vein connects to the right portal vein. Patients with RSLT frequently have hepatic vasculature and bile duct anomalies, which increase the risk of complications with hepatectomy. Most patients with RSLT undergo open hepatectomy. We describe a patient with RSLT and hepatocellular carcinoma who underwent laparoscopic hepatectomy. The patient was a 69-year-old man with hepatocellular carcinoma located in the left liver based on computed tomography (CT) and magnetic resonance imaging. Imaging also demonstrated RSLT. Three-dimensional CT analysis revealed independent right lateral type anomalies of the portal vein and bile duct. Laparoscopic extended left lateral sectionectomy was performed after careful surgical planning. Ultrasonography was used frequently during surgery to avoid damaging the right hepatic vasculature. The left lateral and partial left median sections were removed as planned. The patient’s postoperative recovery was uneventful. Avoiding injury to the right hepatic vasculature is essential when performing left lobectomy, including left lateral sectionectomy, in patients with RSLT. Laparoscopic hepatectomy can be performed safely in patients with RSLT, provided that careful surgical planning is conducted using preoperative three-dimensional CT analysis and intraoperative ultrasonography is used.

Political and legal debate about freedom of religion and belief (FoRB) in Australia has intensified since the Same-sex marriage postal survey in 2017. Central to this debate has been children, their parents and institutions (Schools). This paper outlines the place of children in the Australian FoRB since 2017, focusing on the Same-sex marriage postal survey debate and subsequent reviews into freedom of religion. In particular it highlights the links drawn between same-sex marriage or marriage equality and the Safe School Coalition Australia campaign, the emphasis on parental rights in relation to education about marriage in schools and the ongoing debate about potential reform to Australia’s suit of anti-discrimination laws

SIRT6 is a NAD+ dependent enzyme and stress response protein that has sparked the curiosity of a plethora of researchers in different branches of the biomedical sciences. A unique member of the known Sirtuin family, SIRT6 has several different functions in several different molecular pathways related to DNA repair, glycolysis, gluconeogenesis, tumorigenesis, neurodegeneration, cardiac hypertrophic responses and so on. Only in recent times however did the potential usefulness of SIRT6 come to light as we learned more about its biochemical activity, regulation, biological roles and structure [1]. Even until very recently, SIRT6 was known more for chromatin signaling but being a nascent topic of study, more information has been ascertained and its potential involvement in major human diseases namely, diabetes, cancer, neurodegenerative diseases and heart disease has been demonstrated. It is pivotal to explore the mechanistic workings of SIRT6 since future research may hold the key to engendering strategies, involving SIRT6, that may have significant implications for human health and expand upon possible treatment options. In this review, we are primarily concerned with exploring the latest understanding of SIRT6 and how it can alter the course of several life-threatening diseases that cripple today’s society such as processes related to aging, cancer, neurodegenerative diseases, heart disease and diabetes. In addition, SIRT6 has shown to be involved in liver disease, inflammation and bone related issues but more emphasis is given to the former. Lastly, any recent promising pharmacological investigations and study of potential therapeutic targets are also delineated in this review.

Hypoxia can induce pulmonary edema (PE) and inflammation. Furthermore, hypoxia depresses left ventricular (LV) inotropy despite sympathetic activation. Here, we investigated the role of nitrosative stress and cardiovascular dysfunction in hypoxic lung injury. Additionally, we studied effects of adrenergic blockade (AB) on hypoxia-induced pulmonary injury. Eighty-six female rats were exposed for 72 h to normoxia or normobaric hypoxia and received infusions with NaCl, prazosin, propranolol or prazosin-propranolol combination. We evaluated hemodynamic function and performed histological and immunohistochemical analyses of the lung. Hypoxia significantly depressed LV but not right ventricular (RV) inotropic and lusitropic functions. AB significantly decreased LV function both in normoxia and hypoxia. AB effects on RV were weaker. Hypoxic rats showed signs of moderate PE and inflammation. This was accompanied by elevated levels of tumor necrosis factor (TNF)  and nitrotyrosine, a marker of nitrosative stress in the lungs. In hypoxia, all types of AB significantly reduced both TNF and nitrotyrosine to normoxic levels. However, AB did not attenuate PE. Results suggest that hypoxia-induced sympathetic activation contributes to inflammation and nitrosative stress in the lungs but not to PE. We suggest that AB in hypoxia aggravates hypoxia-induced inotropic LV dysfunction and backlog into pulmonary circulation, thus promoting PE.

While investigating the outcomes of balloon dilatation procedures in patients with congenital obstructive lesions of the heart, several parallel observations have been made. The purpose of this review is to present these observations/phenomena/innovations related to balloon dilatation of pulmonary stenosis (PS), aortic stenosis (AS), and aortic coarctation (AC). In subjects who had balloon pulmonary valvuloplasty (BPV), development of infundibular obstruction, electrocardiographic (ECG) changes, changes in right ventricular filling, role of balloon/annulus ratios on the results of BPV, and double balloon vs. single balloon BPV will be reviewed. In patients who had balloon aortic valvuloplasty (BAV), causes of aortic insufficiency and trans-umbilical venous approach for BAV will be tackled. In children who had balloon angioplasty (BA) of AC, aortic remodeling and biophysical response after BA of AC will be discussed.

Wearable and mobile technology has advanced in leaps and bounds in the last decade with technological advances creating a role from enhancing healthy living to monitoring and treating disease. However, the discussion about the ethical use of such commercial technology in the community, especially in minors, is lacking behind. In this paper, we first summarize the major ethical concerns that arise from the usage of commercially available wearable technology in children, with a focus on smart watches, highlighting issues around the consent process, mitigation of risk and potential confidentiality and privacy issues, as well as the potential for therapeutic misconceptions when used without medical advice. Then through a relevant thought experiment we move on to outline some further ethical concerns that are connected to the use of wearables by minors, to wit the issue of informed consent in the case of minors, forcing them to live in the spotlight, and compromising their right to an open future. We conclude with the view that mitigating potential pitfalls and enhancing the benefits of wearable technology especially for minors requires brave and comprehensive moral debates.

Background: Access to rehabilitation is crucial for the realization of the right to health and a proper concern of global health. Yet, reliable information to guide rehabilitation service planning is unavailable in many countries in part due to the lack of appropriate indicators. To ensure universal health coverage and meet the central imperative of “leaving no one behind” countries must be able to assess key aspects of rehabilitation policy and provision and monitor how they have discharged their human rights responsibilities towards those most disadvantaged, including people with disability. This article describes the process of developing an expert guided indicator framework to assess governments’ efforts and progress in strengthening rehabilitation in line with the Convention on the Rights of Persons with Disabilities. Methods: A systems methodology - concept mapping - was used to capture, aggregate and confirm the knowledge of diverse stakeholders on measures thought to be useful for monitoring the implementation of the Convention with respect to health related rehabilitation. 56 individuals generated a list of 107 indicators through online brainstorming which were subsequently sorted by 37 experts from the original panel into non overlapping categories. 41 participants rated the indicators for importance and feasibility. Multivariate statistical techniques where used to explore patterns and themes in the data and create the indicators’ organizing framework which was verified and interpreted by participants. Results: A concept map of 11 clusters of indicators emerged from the analysis grouped into three broader themes: Governance and Leadership (3 clusters); Service Delivery, Financing and Oversight (6 clusters); and Human Resources (2 clusters). The RESYST was comprehensive and well aligned with the Convention. On average, there was a moderately positive correlation between importance and feasibility of the indicators (r=.58) with experts prioritizing the indicators contained in the clusters of the Governance and Leadership domain. Two of the most important indicators arose from the Service Delivery, Financing and Oversight domain and reflect the need to monitor unmet needs and barriers in access to rehabilitation. In total, 59 indicators achieved above average score for importance and comprised the two–tiered priority set of indicators. Conclusion: Concept mapping was successful in generating a shared model that enables a system’s view of the most critical legal, policy and programmatic factors that must be addressed when assessing country efforts to reform, upscale and improve rehabilitation services. The RESYST provides a data driven basis for the development of standardized data collection tools to facilitate comparative analysis of rehabilitation systems.

Background: Antiphospholipid antibodies (aPL) are a laboratory criterion for the classification of antiphospholipid syndrome (APS), and are known to cause clinical symptoms: vascular thrombosis or obstetric complications. It is suggested that aPL may be associated with thromboembolism in severe COVID-19 cases. Aim: to combine clinical data with aPL findings at 4 time points (admission, worsening, discharge, 3-month follow-up) in patients hospitalized with COVID-19 pneumonia. Methods: current and past history of thrombosis and obstetric complications; aPL determined at 4 time points: anticardiolipin (aCL), anti-β2-glycoprotein I (anti- β2GPI) and antiphosphatidylserine/prothrombin (aPS/PT) of the IgM, IgG or IgA isotypes. Results: 111 patients with COVID-19 pneumonia were enrolled. During hospitalization, 7 patients died, 3 of them due to pulmonary artery thromboembolism (none was aPL positive). Only one of the five who developed pulmonary artery thrombosis was aPL positive. Of 9/101 patients with a history of thrombosis, 5 had arterial thrombosis and none was aPL positive at admission and follow-up; 4 had venous thrombosis and one was aPL positive at all time points (newly diagnosed APS). Of these 9/101 patients, 55.6% were transiently aPL positive at discharge only, compared to 26.1% without history of thrombosis (p=0.05). Conclusions: aPL were not associated with fatal outcomes and vascular thrombosis; aPL were transiently positive in more than half of patients with a history of thrombosis.

Transformer models have emerged as frontrunners in the field of natural language processing, primarily due to their adept use of self-attention mechanisms to grasp the semantic linkages between words in sequences. Despite their strengths, these models often face challenges in single-task learning scenarios, particularly when it comes to delivering top-notch performance and crafting strong latent feature representations. This challenge is more pronounced in the context of smaller datasets and is particularly acute for under-resourced languages such as Arabic. In light of these challenges, this study introduces a novel methodology for text classification of Arabic texts. This method harnesses the newly developed Reverse Positional Encoding (RPE) technique. It adopts inductive-transfer learning (ITL) framework combined with a switching self-attention shared encoder, thereby increasing the model's adaptability and improving its sentence representation accuracy. The integration of Mixture of Experts (MoE) and Reverse Positional Encoding (RPE) techniques empowers the model to process longer sequences more effectively. This enhancement is notably beneficial for Arabic text classification, adeptly supporting both the intricate five-point and the simpler ternary classification tasks. The empirical evidence points to its outstanding performance, achieving accuracy rates of 87.20% for the HARD dataset, 72.17% for the BRAD dataset, and 86.89% for the LABR dataset, as evidenced by the assessments conducted on these datasets.

Manufacturing environments, characterized by rapid, unpredictable changes, uncertainties, risks, and uncontrollable fluctuations, pose significant challenges to minimizing disruptions in processes. This study introduces an innovative approach that prioritizes curbing risk propagation among processes to enhance robustness. It emphasizes the integration of engineering management principles and modular design within manufacturing. Adopting a system engineering perspective, all manufacturing process activities are viewed as interrelated components within a unified system. By employing Axiomatic Design (AD) theory and the Design Structure Matrix (DSM) method, manufacturing process architecture is modularized, yielding heightened robustness. The proposed mathematical model equips engineering and manufacturing managers with a potent tool for designing robust processes while adeptly managing system complexity. The study's outcomes underscore a substantial enhancement in modularization, leading to elevated overall robustness in manufacturing processes. To validate the methodology, the architectural design of manufacturing processes is examined in a real-case scenario, specifically the Barez Industrial Group in Iran. This verification substantiates the 'manufacturing processes' of the case, presenting an optimally modularized architecture. The results affirm the proposed approach's efficacy, demonstrating improved modularization that contributes to bolstered robustness in manufacturing processes.

Chronic traumatic encephalopathy (CTE) is a unique neurodegenerative disease that is associated with repetitive head impacts (RHI) in both civilian and military settings. In 2014, the research criteria for the clinical manifestation of CTE, traumatic encephalopathy syndrome (TES) were proposed to improve the clinical identification and understanding of the complex neuropathological phenomena underlying CTE. This review provides a comprehensive overview of the current understanding of the neuropathological and clinical features of CTE, proposed biomarkers of traumatic brain injury (TBI) in both research and clinical settings, and a range of treatments based on previous preclinical and clinical research studies. Due to the heterogeneity of TBI, there is no universally agreed-upon serum, CSF, or neuroimaging marker for its diagnosis. However, as our understanding of this complex disease continues to evolve, it is likely that there will be more robust, early diagnostic methods and effective clinical treatments. This is especially important given the increasing evidence of a correlation between TBI and neurodegenerative conditions, such as Alzheimer's disease and CTE¹. As public awareness of these conditions grows, it is imperative to prioritize both basic and clinical research, as well as the implementation of necessary safe and preventative measures.

Patients with neurodegenerative diseases (NDDs) are rapidly increasing all over the world. Alzheimer’s disease (AD), Parkinson’s disease, Huntington’s disease (HD), frontotemporal lobar degeneration (FTLD) and many other diseases are classified as NDDs, however, no therapeutic drugs have been developed against NDDs yet. As common phenomenon, protein oligomers and aggregates (inclusion bodies) are formed in neurons, and they trigger neuronal cell death and/or axonal degeneration. We have investigated the mechanisms of NDDs, and discovered several chemicals and peptides have potential to cure NDDs. Here, we show phorbol 12-myristate 13-acetate (PMA) significantly inhibits aggregate formation and promotes neurite regeneration in human neuronal cell culture model of NDDs, FTLD and AD. We expressed R406W mutant tau protein found in FTLD patients in human neuroblastoma SH-SY5Y cells as FTLD cell culture model. These FTLD neuronal cells showed intracellular aggregate formation and impaired neurite growth. Addition of PMA to culture medium 60% suppressed aggregate formation. PMA also enhanced neurite growth to the normal level at nanomolar concentration. We cultured SH-SY5Y cells in the medium containing -amyloid (1-42) as AD cell culture model. In these cells, neurite growth was limited to less than 50% of controls by the treatment of -amyloid (1-42). Surprisingly, addition of PMA increased the number of cells with >10-fold neurite extension to seven times even in -amyloid (1-42) contained medium. Also, PMA increased the expression of several genes and proteins important for cell survival in both cell culture models. These results suggest PMA has unexpected potential for the drug development against NDDs.

Alzheimer's Disease (AD) represents the most frequent type of dementia in elderly people. There are two major forms of the disease: sporadic (SAD) - whose causes are not completely understood - and familial (FAD) - with clear autosomal dominant inheritance. The two main hallmarks of AD are extracellular deposits of amyloid-beta (Ab) peptide and intracellular deposits of the hyperphosphorylated form of the tau protein (P-tau). An ever-growing body of research supports the infectious hypothesis of sporadic forms of AD. Indeed, it has been documented that some pathogens, such as herpesviruses and certain bacterial species, are commonly present in AD patients, prompting recent clinical research to focus on the characterization of Antimicrobial Peptides (AMPs) in this pathology. Literature also demonstrates that Ab can be considered itself as an AMP thus representing a type of innate immune defense peptide that protect the host against a variety of pathogens. Beyond Ab, other proteins with antimicrobial activity, such as lactoferrin, defensins, cystatins, thymosin β4, LL37, histatin 1 and statherin have been shown to be involved in AD. Here we have summarized and discussed these findings and explored the diagnostic and therapeutic potential of AMPs in AD.

The number of people owning vehicles has been steadily growing, resulting in increased numbers of vehicles on the roads, making roads more congested, and increasing the risk of accidents. In addition, heavy rain, snow, and fog have increased due to abnormal weather caused by global warming. These bad weather conditions can also affect the safety of vehicles and drivers. The need to disseminate safety messages on the social internet of vehicles due to these problems has been steadily increasing. In this paper, we propose an efficient safety message dissemination scheme that focuses on urban environments with high vehicle density and mobility to address these problems. The proposed scheme reduces packet loss by considering frequent cluster departures and subscriptions through an efficient cluster management technique. In a vehicle-to-vehicle environment, the dissemination of safety messages is divided into an intra-cluster and an inter-cluster emergency as well as general safety message dissemination technique. In a vehicle to infrastructure environment, the proposed scheme reduces the number of processing requests and duplicate messages made to roadside units (RSUs) through a request operation process for each vehicle and an RSU scheduling technique. We conducted several performance evaluations of message packet loss and the number of RSU processing requests to demonstrate the superiority of the proposed scheme.

Considering the controversial benefits of video-assisted thoracoscopic surgery (VATS), we intended to evaluate the impact of surgical approach on cardiac function after lung resection using myocardial work analysis. Echocardiographic data of 45 patients (25 thoracotomy vs. 20 VATS) were retrospectively analyzed. All patients underwent transthoracic echocardiography (TTE) 2 weeks before and after surgery, including two-dimensional speckle tracking and tissue doppler imaging. No notable changes in left ventricular (LV) function, assessed mainly using the LV global longitudinal strain (GLS), global myocardial work index (GMWI), and global work efficiency (GWE), were observed. Right ventricular (RV) TTE values, including tricuspid annular plane systolic excursion (TAPSE), tricuspid annular systolic velocity (TASV), and RV free-wall GLS (RVFWGLS), indicated greater RV function impairment in the thoracotomy group than in the VATS group [TAPSE (mm): 17.90 ± 3.80 vs. 20.60 ± 3.50, p < 0.018; TASV (cm/s): 12.40 ± 2.90 vs. 14.60 ± 2.50, p < 0.010; RVFWGLS (%): −11.50 ± 8.50 vs. −17.50 ± 9.70, p < 0.033), respectively]. Unlike RV function, LV function remained preserved after lung resection. The thoracotomy group exhibited greater RV function impairment than did the VATS group. Further studies should evaluate the long-term impact of surgical approach on cardiac function.

The airport ground handling service (AGHS) equipment vendor selection (AGHSEVS) problem is critical for ramp work safety management, because AGHS equipment malfunctions affect airport ramp work safety. Appropriate vendor selection can prevent aircraft damage and delays in airlines schedules, and ensure reliable and high-quality ground handling service. The AGHSEVS problem is a time-consuming and complex process that requires professional knowledge and experience to make judgments. Specifically, AGHSEVS is a multi-criteria decision-making (MCDM) problem. Previous research has seldom integrated MCDM methods with linear and goal programming to solve the AGHSEVS problem. The objective of this study was to develop a new system evaluation model for AGHSEVS by considering both qualitative and quantitative methods. We test the proposed approach on an AGHS company in Taiwan.

A cross-flow ultrafiltration harvesting system of a pre-concentrated microalgae culture was tested in an innovative anaerobic-based WRRF. The microalgae culture was cultivated in a membrane photobioreactor fed with the effluent from an anaerobic membrane bioreactor treating sewage. These harvested microalgae biomass was then anaerobically co-digested with primary and secondary sludge from the water line. Depending on the needs of this anaerobic co-digestion, the filtration harvesting process was evaluated intermittently over a period of 212 days for different operating conditions, mainly the total amount of microalgae biomass harvested and the desired final total solids concentration (up to 15.9 g·L1 with an average of 9.7 g·L1). Concentration ratios of 15-27 were obtained with average transmembrane fluxes ranged from 5 to 28 L·m2·h1. Regarding membrane cleaning, both backflushing and chemical cleaning resulted in transmembrane flux recoveries that were, on average, 21% higher than those achieved with backflushing alone. The carbon footprint assessment shows promising results as the GHG emissions associated with the cross-flow ultrafiltration harvesting process could be less than the emissions savings associated with the energy recovered from the biogas production from the anaerobic valorisation of the harvested microalgae.

In this study, the fundamentals of electroencephalography signals, their categorization into frequency sub-bands, the circuitry used for their acquisition, and the impact of noise interference on signal acquisition are examined. Additionally, design specifications for medical-grade and research-grade EEG circuits and a comprehensive analysis of various analog front-end architectures for electroencephalograph (EEG) circuit design are presented. Three distinct selected case studies are examined in terms of comparative evaluation with generic EEG circuit design templates. Moreover, a novel one-channel battery-supplied EEG analog front-end circuit designed to address the requirements of usage protocols containing strong com-pound muscle movements is introduced. Furthermore, a realistic input signal generator circuit is proposed that models the human body and the Electromagnetic Interference from its surroundings. Experimental simulations are conducted in 50 Hz and 60 Hz electrical grid environments to evaluate the performance of the novel design. The results demonstrate the efficacy of the proposed system, particularly in terms of bandwidth, portability, common mode rejection ratio , gain, suppression of muscle movement artifacts, electrostatic discharge and leakage current protection. Conclusively, the novel design is cost-effective and suitable for both commercial and research single-channel EEG applications. It can be easily incorporated in Brain Computer Interfaces and neurofeedback training systems.

There are no investigations about the outcomes of idiopathic PVCs catheter ablation (CA) in athletes compared to sedentary population. We conducted a prospective single-centre observational study. The primary and secondary procedural outcomes were premature ventricular contractions (PVCs) post-ablation reduction in athletes vs. non-athletes group and in agonist vs. leisure-time athletes. The third was the evaluation of the resumption of physical activity and the improvement of symptoms in agonist and leisure-time athletes. From January 2020 to October 2022 we enrolled 79 patients with RVOT/LVOT/fascicular PVC presumed origin. The median percentage of decrease between the pre-procedure and post-procedure Holter monitoring in non-athletes group was 96 (IQR 68 – 98) and 98 in athletes group (IQR 92 – 99) (p=0,08). Considering the athletes, the median percentage of decrease in PVCs number was 98 (IQR 93-99) and 98 (IQR 87-99) respectively in leisure-time and agonistic athletes (p=0,42). Sixteen (70%) leisure time and 17 (90%) agonist athletes (p=0,24) have resumed physical activity 3 months after PVCs CA; among agonistic athletes, 59% have resumed competitive physical activity. Much of leisure-time (88%) and agonist (70%) athletes experienced an improvement in symptoms after ablation. PVC CA was effective and safe in both groups, reducing symptoms and allowing a quick and safe return to sports activities in athletes.

The time symmetry of T_c = CT is redefined based on the 4-D Euclidean space. The time inversion symmetry of T_c = CT changes the signs of the charge (q) and absolute time (ct) of the particle. The P symmetry changes the signs of the space momenta and handedness of the particle. The T_c symmetry changes the signs of the time momentum (P_t=E/c) and charges. The handedness are classified as the left-handedness and right-handedness on the 3-D space. The charges (|q| = cDt) and energies (E= cDtDV) of the particles are originated from the upward warping (q>0) and downward warping (q<0) of the particles along the time axis. The evolution of our matter universe with P_t > 0 since the big bang can be interpreted based on the CTP symmetry with the partner antimatter universe with p_t < 0. The photon space is called as the vacuum space. Then the E and M waves are the space fluctuations, and the gravitational G wave is the time fluctuations. And the E, M and G fields are newly explained. The zero E and M fields of the photon space indicates that the photon space and gamma ray are the 2EM waves. The rest mass energy of the particle is the 4-D space volume of the warped photon space. In the present work, the quantum wave function is considered as the 4-D vector with the space wave function and time axis wave function in the 4-D Euclidean space. The warped photon space corresponds to the squared wave function which is the probability density. It is concluded that, in the quantum mechanics, the imaginary number concept is introduced in the quantum wave functions instead of the time axis component of the 4-D wave function vector. The left-handed neutrino puzzle is explained from the handedness partner relation with the right-handed dark matters. Finally, the modified Lorentz transformations derived in the 4-D Euclidean space are compared with the Lorentz transformations of the special and general relativity theories in the 4-D Minkowski space.

Effective therapeutics for Alzheimer's disease (AD) are in great demand worldwide. In our previous work, we responded to this need by synthesizing novel drug candidates consisting of 4-amino-2,3-polymethylenequinolines conjugated with butylated hydroxytoluene via fixed-length alkylimine or alkylamine linkers (spacers) and studying their bioactivities pertaining to AD treatment. Here, we report significant extensions of these studies, including the use of variable-length spacers and more detailed biological characterizations. Conjugates were potent inhibitors of acetylcholinesterase (AChE, minimum IC50 15.1±0.2 nM) and butyrylcholinesterase (BChE, minimum IC50 5.96±0.58 nM), with weak inhibition of off-target carboxylesterase. Conjugates with alkylamine spacers were more effective cholinesterase inhibitors than alkylimine analogs. Optimal inhibition for AChE was exhibited by cyclohexaquinoline and for BChE by cycloheptaquinoline. Increasing spacer length elevated potency against both cholinesterases. Structure-activity relationships agreed with docking results. Mixed-type reversible AChE inhibition, dual docking to catalytic and peripheral anionic sites, and propidium iodide displacement suggested the potential of hybrids to block AChE-induced β-amyloid (Aβ) aggregation. Hybrids also exhibited inhibition of Aβ self-aggregation in the thioflavin test; those with a hexaquinoline ring and C8 spacer were the most active. Conjugates demonstrated high antioxidant activity in ABTS and FRAP assays as well as inhibition of luminol chemiluminescence and lipid peroxidation in mouse brain homogenates. Quantum-chemical calculations explained antioxidant results. Computed ADMET profiles indicated favorable blood-brain barrier permeability suggesting CNS activity potential. Thus, the conjugates could be considered promising multifunctional agents for potential treatment of AD.

Background: In this study, we aimed to evaluate the effect of s-FLT-1 and PlGF concentrations in women in the first trimester of pregnancy on the pulsatility index of the ductus venosus and the right and left uterine arteries. Methods: A total of 108 pregnant women in their first trimester were included in the study, with 87 assigned to the experimental group and 21 to the control group. Ultrasound examination were performed to measure the uterine artery pulsatility index, resistance index, ductus venosus pulsatility index, and blood sampling levels of biomarkers such as b-HCG; PAPP-A; s-FLT-1 and PlGF. Results: There was a significant negative relationship between PAPP-A concentration and the risk of fetal growth restriction, and a significant negative relationship between PlGF concentration and the risk of preeclampsia and fetal growth restriction in women in their first trimester of pregnancy. There was also a significant positive relationship between sFLT-1/PLGF ratio and the risk of developing preeclampsia. No significant relationships were found between the concentrations of biomarkers beta-HCG, PAPP-A, sFLT-1, PlGF, and any of the parameters PIUARt, PIUALt, Mean uterine arteries, and DVPI. Summary: In conclusion, this study did not find conclusive evidence to support the hypothesis that beta-HCG, PAPP-A, s-FLT-1, and PlGF concentrations in women in the first trimester of pregnancy have a significant effect on the Pulsatility Index of the ductus venosus and the Right and left Uterine Arteries. Further research is needed to investigate these potential associations.

The assessment of welfare and disease progression in animal models is critical. Most tools rely on evaluating individual subjects, whereas social behaviors, also sensitive to acute illness, chronic diseases, or mental health, are scarcely monitored because of their complexity, are invasive, and time-consuming. We propose the evaluation of social nesting, a species-typical behavior naturally occurring in standard housing conditions, for such behavioral monitoring. We provide an example of its use to evaluate social deficits and the long-term effects of neonatal sensorial stimulation in male and female adult 3xTg-AD mice for Alzheimer's disease compared to sex- and age-matched NTg counterparts with normal aging. Social nesting was sensitive to genotype (worse in 3xTg-AD mice), sex (worse in males), profile, and treatment (distinct temporal patterns, time to observe the maximum score and incidence of the perfect nest). Since social nesting can be easily included in housing routines, this neuroethological approach can be useful for animal's welfare, monitoring the disease's progress, and evaluating potential risk factors and effects of preventive/therapeutical strategies. Finally, the non-invasive, painless, simple, short time and low-cost features of this home-cage monitoring are advantages that make social nesting feasible to be successfully implemented in most animal department settings.

The outflow tract of crocodilians resembles that of birds and mammals as ventricular septation is complete. The arterial anatomy however, presents with a pulmonary trunk originating from the right ventricular cavum, and two aortae originating from either the right or left ventricular cavum. Mixing of blood in crocodilians cannot occur at ventricular level as in other reptiles, but instead takes place at aortic root level by a shunt, the Foramen of Panizza, the opening of which is guarded by two facing semilunar leaflets of both bicuspid aortic valves. Methods. Developmental stages of Alligator mississipiensis, Crocodilus niloticus and Caiman latirostris, have been studied. Results and Conclusions. The outflow tract septation complex can be divided into 2 components. The aorto-pulmonary septum divides the pulmonary trunk from both aortae, whereas the interaortic septum divides the systemic from the visceral aorta. Neural crest cells are most likely involved in the formation of both components. Remodeling of the endocardial cushions and both septa results in the formation of bicuspid valves in all three arterial trunks. The foramen of Panizza originates intracardially as a channel in the septal endocardial cushion.

Alzheimer’s Disease (AD) has no cure. Earlier, we showed that partial inhibition of mitochondrial complex I (MCI) with small molecule CP2 induces adaptive stress response activating multiple neuroprotective mechanisms. Chronic treatment reduced inflammation, improved synaptic and mitochondrial functions, and blocked neurodegeneration in symptomatic APP/PS1 mice, a translational model of AD. Here, using serial block-face scanning electron microscopy (SBFSEM) and three-dimensional (3D) EM reconstructions combined with Western blot analysis and next-generation RNA sequencing, we demonstrate that CP2 treatment also restores mitochondrial morphology and mitochondria-endoplasmic reticulum (ER) communication in the APP/PS1 mouse brain. Using 3D EM volume reconstructions, we show that mitochondria in AD dendrites exist primarily as mitochondria-on-a-string (MOAS). Compared to other morphological phenotypes, MOAS are extensively enveloped in the ER membranes forming multiple mitochondria-ER contact sites (MERCS) known to contribute to abnormal lipid and calcium homeostasis. CP2 treatment specifically reduced MOAS formation, consistent with improved energy homeostasis in the brain, with concomitant reduction in MERCS, ER stress, and improved lipid homeostasis. These data provide novel information on the role MOAS play in AD and additional support for further development of partial MCI inhibitors as disease modifying strategy for AD.

A large body of evidence, replicated in many mouse models of Alzheimer Disease (AD), demonstrated the therapeutic efficacy of oral rapamycin. Administration of m-TOR inhibitors (mTOR-Is), early after the clinical onset, greatly diminished cognitive impairment, amyloid angiopathy, intracellular beta Amyloid and neurofibrillary tangles load. The daily intake of rapamycin has always been 2.24g/Kg/24h. In humans the maximal tolerated oral dose is a few milligrams/day, and at this dosage patients are severely immunosuppressed. Thanks to rapalogs’ scarce CNS-related side effects, we administered intracerebroventricularly (ICV) high doses of the mTOR-I everolimus in a mouse model of AD (3xTg-AD) without significant systemic effects. The instability of the liquid formulation at body temperature (BT) made the treatment very short. Nevertheless, the efficacy of the treatment was high and much longer lasting than expected. In order to set up a thermostable, translational liquid formulation of mTOR-Is, we loaded everolimus in distearoylphosphatidylethanolamine-polyethylene glycol 2000 (DSPE-PEG2000) micelles by the thin layer method. The formulation we obtained maintained over 95% of activity after 14 days at BT. We can envision short, potentially periodic ICV treatments in AD patients which replicate results obtained on animal models. The treatment could benefit also Tuberous Sclerosis and Multiple Sclerosis patients.

Premature ovarian insufficiency (POI) is a highly prevalent disorder, characterized by the development of menopause before age of 40. Most cases are idiopathic; however, in some women the cause of this condition (e.g. anticancer treatment, genetic disorders, and enzymatic defects) may be identified. Although hormone replacement therapy, the principal therapeutic approach for POI, helps to alleviate the related symptoms, this does not effectively solve the issue of fertility. Assisted reproductive techniques also lack efficacy in these women. Thus, the effective approach to manage the patients with POI is highly warranted. Several mechanisms, associated with POI, have been identified, including lack of FSH receptor functioning, alterations in the apoptosis control, mutations in Sal-like 4 genes, thymulin or basonuclin-1 deficiency etc. The above-mentioned may be good targets for gene therapy in order to correct defects, leading to POI. The goal of this review is to summarize the current experience on the POI studies, that employed gene therapy, and to discuss the possible future directions in this field.

The Internet of Things (IoT) is a technological paradigm that has gained significant momentum that last decade and, among others, enables the development of intelligent and interoperable device networks. In this respect, it has triggered the creation and evolution of VANETs (Vehicular Ad Hoc Networks), which are initially implemented in order to guarantee the safety of the drivers and the avoidance of traffic accidents. The drawback is that this fast evolution flags serious concerns as far as the privacy of users is concerned, while the population of attackers or entities that try to eavesdrop and intercept information has significantly increased. This imposes a serious risk for drivers moving across a Smart City. The research presented in this paper aims to evaluate privacy protection mechanisms in VANET environments, based on their efficiency and security level ensured, considering the fact that VANETs provide limited resources to users/drivers. Moreover, the usage of the elliptic curve cryptography in reduced resources environments is discussed. Finally, this paper compares the performance of three cryptographic algorithms, i.e., Elliptic Curve Cryptography (ECC), Hyperelliptic Curve Cryptography genus 2 (HECC-2) and HECC genus 3 (HECC-3), employed for an efficient authentication and safe message transmission mechanism in VANETs, targeting to extract conclusions related to the implementation of each cryptographic scheme in this specific application area.

Cardiomyopathies are diseases of heart muscle, a significant percentage of which are genetic in origin. Cardiomyopathies can be classified as dilated, hypertrophic, restrictive, arrhythmogenic right ventricular or left ventricular non-compaction, although mixed morphologies are possible. A subset of neuromuscular disorders, notably Duchenne and Becker muscular dystrophies, are also characterized by cardiomyopathy aside from skeletal myopathy. The global burden of cardiomyopathies is certainly high, necessitating further research and novel therapies. Genome editing tools, which include zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR) systems have emerged as increasingly important technologies in studying this group of cardiovascular disorders. In this review, we discuss the applications of genome editing in the understanding and treatment of cardiomyopathy. We also describe recent advances in genome editing that may help improve these applications, and some future prospects for genome editing in cardiomyopathy treatment.

Vehicle-to-Vehicle (V2V) communication plays a pivotal role in modern intelligent transportation systems, enabling seamless information exchange among vehicles to enhance road safety, traffic efficiency, and overall driving experience. However, the secure transmission of sensitive data between vehicles remains a critical concern due to potential security threats and vulnerabilities. This research paper focuses on investigating the security protocols employed in Vehicle-to-Vehicle communication systems. A comprehensive review and analysis of relevant literature and research papers is conducted to gather information on existing V2V communication security protocols and techniques. The analysis encompasses key areas, including authentication mechanisms, encryption algorithms, key management protocols, and intrusion detection systems specifically applicable to V2V communication networks. Within the context of real-world V2V environments, this study delves into the challenges and limitations associated with implementing these protocols. Moreover, to foster a deeper understanding, the paper investigates present communication protocols in the field of Internet of Things (IoT) that are tailored for V2V. Various parameters, such as band-width consumption, energy consumption, latency, and message size, are considered during the evaluation of these protocols to gauge their effectiveness. The research outcomes aim to provide a comprehensive understanding of the strengths and weaknesses of the current V2V communication security protocols. Furthermore, based on the findings, this paper will propose improvements and recommendations to enhance the security measures of the V2V communication protocol. Ultimately, this research will contribute to the development of more secure and reliable V2V communication systems, propelling the advancement of intelligent transportation technology.

Human endogenous retroviruses (HERV) are remnants of ancient retroviral infections that, over millions of years, became integrated into the human genome. While normally inactive, environmental stimuli such as infections have contributed to the transcriptional reactivation of HERV promoting pathological conditions including the development of autoimmunity, neurodegenerative disease and cancer. What infections then trigger HERV activation? Mycobacterium avium subspecies paratuberculosis (MAP) is a pluripotent driver of human disease. Aside from granulomatous diseases Crohn’s, sarcoidosis and Blau syndrome, MAP is associated with autoimmune disease: type one diabetes (T1D), multiple sclerosis (MS), rheumatoid arthritis and autoimmune thyroiditis. MAP is also associated with Parkinson’s disease. Autoimmune diabetes, multiple sclerosis and rheumatoid arthritis are the diseases with the strongest MAP/HERV association. There are several other diseases associated with HERV activation including diseases whose epidemiology and/or pathology would prompt speculation for a causal role of MAP. These include non-solar uveal melanoma, colon cancer, glioblastoma and amyotrophic lateral sclerosis (ALS). This article further points to MAP infection as a contributor to autoimmunity, neurodegenerative disease and cancer via unsilencing of HERV. We examine the link between the ever-increasing number of MAP- associated diseases, the MAP/HERV intersection with these diverse medical conditions and propose treatment opportunities based upon this association.