Introduction: Substance-induced psychotic disorder (SIPD) is a mental health condition linked to the use of a psychotropic substance whose pathogenesis has not been totally clarified. The present retrospective observational study has the objective to identify differences in clinical features and peripheral biomarkers in SIPD patients according to the main substance of abuse.Methods: A total sample of 218 patients was divided in 3 groups according to the type of consumed substance: alcohol, cannabis and psychostimulants. The 3 groups were compared for continuous variables by one-way analyses of variance (ANOVAs) and for qualitative variables by χ² tests. After removing alcohol-induced psychotic disorder group, the same analyses were repeated. Statistically significant variables from these latter analyses were included in a binary logistic regression model to confirm their reliability as predictors for cannabis- or psychostimulants-induced psychotic disorders. Results: Psychotic cannabis abusers were younger (p<0.01) and had an earlier age at onset (p<0.01). On the contrary, alcohol consumers resulted to have a longer duration of illness (p<0.01), more previous hospitalizations (p=0.04), more frequent medical comorbidity (p<0.01), higher mean Modified Sad Person Scale scores (p<0.01). Finally, psychostimulant abusers had more frequently a lifetime history of poly-substance use disorders (p<0.01). Binary logistic regression revealed that higher mean Brief Psychiatric Rating Scale scores (p<0.01) higher sodium (p=0.012) and haemoglobin(p=0.040) plasma levels were predictors of cannabis misuse in SIPD patients.Conclusions: Different clinical factors and biochemical parameters con be associated to SIPD according to the main substance of abuse, thus requiring a specific management by clinicians.

Many drastic actions are taken by cocaine users for the sake of experiencing high dopamine levels, which depends on iron for its synthesis. Dopamine depletion and iron deficiency are also involved in the symptoms of restless leg syndrome (RLS). The intersecting biochemical pathways of cocaine use, iron deficiency, and RLS have not been adequately investigated. This case report reveals the successful treatment of a patient with these conditions. A 63-year-old male with a history of cocaine use disorder, insomnia, and RLS sought emergency care for suicidality. Upon admission, he was also found to be iron-deficient. He revealed that his RLS worsened when he attempted to abstain from cocaine. He also used alcohol to sustain the effects of cocaine when the cost of cocaine was too high. During hospitalization, his mood, cravings, and RLS were resolved with adjunctive iron supplementation as well as 300 mg of Wellbutrin. If iron-deficient, replenishment of adequate dopaminergic receptor density and function via supplementation may play an essential role in the prevention of cocaine use and cessation of cocaine withdrawal. Further research is warranted to validate these findings and understand the implications of iron supplementation in addiction medicine.

Psychosis can be defined as a combination of psychopathological symptoms including delusions and/or hallucinations without insight. Psychotic disorders may configure a primary psychiatric illness or represent the result of a functional/structural brain damage induced by substance use, neurological diseases or other medical conditions. They are multifactorial disorders in which genetic, environmental and gene-environment interaction factors contribute to the expressiveness of the symptoms. Among the environmental factors, psychotropic substances represent the most important removable facilitators of psychosis. In our study, we compared the prevalence of substance induced psychosis between a sample of patients affected by cannabis use disorder and a sample of patients affected by cocaine use disorder analyzing retrospectively the data of outpatients with no personal or family history of psychiatric illnesses.

Background: Dual disorders (DD) involve the coexistence of substance use disorder (SUD) with another mental illness, often from psychotic and affective categories. This study explores the ef-fectiveness of brexpiprazole, a third-generation antipsychotic, in individuals diagnosed with schizophrenia spectrum disorder (DSM-V) and comorbid AUD/SUD (DSM-V). Methods: Eighteen enrolled patients underwent psychometric assessments at baseline and one month into brexpiprazole treatment administered at a mean dosage of 2 mg/day. Results: Brexpiprazole demonstrated significant reductions in psychopathological burden (PANSS total score, p=0.004), improved CGI total score (p=0.042), and decreased MOAS total score (p=0.012). Quality of life improved in SF-36 subscales (p<0.05). Substance craving reduction, though observed, did not reach statistical significance. Conclusions: This study provides initial evidence supporting brexpiprazole's efficacy and safety with positive effects on psychopathology and quality of life, emphasizing the need for tailored, comprehensive treatment strategies in this complex patient population.

Movement disorders can be associated with various drugs and systemic diseases, posing diagnostic challenges for clinicians. This review explores the spectrum of movement disorders associated with pharmacological agents and medical conditions. Drug-induced movement disorders encompass a broad range of conditions resulting from exposure to medications that affect several neurotransmitters. Neuroleptic medications can lead to tardive dyskinesia, characterized by involuntary, repetitive movements. Antipsychotics and antiemetics, including metoclopramide, may induce acute dystonic reactions. Other drugs, such as dopamine receptor-blocking agents, can contribute to drug-induced parkinsonism. Beyond medications, movement disorders can also arise secondary to systemic diseases. Metabolic disorders like Wilson's disease, characterized by copper accumulation, may manifest as chorea or dystonia. Inflammatory conditions such as rheumatoid arthritis and systemic lupus erythematosus can result in secondary movement disorders due to autoimmune-mediated processes affecting the central nervous system. Movement disorders linked to drugs or systemic diseases often necessitate a thorough clinical evaluation, including detailed medication histories and comprehensive systemic assessments. Neuroimaging, laboratory investigations, and, in some cases, cerebrospinal fluid analyses and electrodiagnostic studies help in establishing accurate diagnoses. Management involves addressing the underlying cause, modifying medications, and employing symptomatic treatments.

Cannabis use disorder (CUD) is a growing public health concern, with rising prevalence and significant impact on individuals across age groups. This systematic review examined pharmacological and psychosocial interventions for CUD among adolescents, young adults, transitioning adults, and older adults. Database searches were conducted for randomized controlled trials of CUD interventions reporting outcomes such as cannabis use, abstinence, withdrawal symptoms, and treatment retention. In total, 53 studies were included. Pharmacological treatments such as cannabinoid agonists, gabapentin, and N-acetylcysteine demonstrated modest benefits predominantly in alleviating withdrawal and craving. Psychosocial approaches including motivational interviewing, cognitive behavioral therapy, and contingency management conferred greater abstinence and retention, either alone or combined with pharmacotherapy. However, age-specific efficacy remains unclear. Technology-based interventions represent promising alternatives to expand access and improve cost-effectiveness. In conclusion, cannabis disorders require expanded, affordable treatment tailored to individuals’ developmental stage. Further research should clarify the utility of harm reduction outcomes and establish age-specific best practices.

Background: Despite the existence of a wide variety of anti-inflammatory drugs, the vast majority are classified as steroidal or non-steroidal. Both classes with many side effects that limit usage. Thus, the search for new molecules with anti-inflammatory potential is still important. Methods: Five phenylbenzohydrazides were synthetized and evaluated in pre-clinical models of acute inflammation in vivo and in vitro. Results: Substances significantly reduced cell migration induced by carrageenan. It was also observed an intense inhibition in protein extravasation and cytokines (IL-6, IL-1β, and TNF-α) production as well as nitric oxide reduction. INL-11 demonstrated to be the most potent since the reduction was significant even when compared with dexamethasone. In vitro INLs also reduced cytokines and NO production and iNOS activity. INL-11 was the most effective in reducing cell migration in vitro. Conclusions: our data suggest that these substances are suitable for further development to new series of compounds that could lead to new hits and future drug prototypes for anti-inflammatory conditions.

Proteomic analysis revealed the preservation of many proteins in the “Heslington brain” (which is at least 2,600-year-old brain tissue uncovered within the skull excavated in 2008 from a pit in Heslington, Yorkshire, England). Five of these proteins (“main proteins”), heavy, medium, and light neurofilament proteins (NFH, NFM, and NFL), glial fibrillary acidic protein (GFAP), and myelin basic (MBP) protein are engaged in the formation non-amyloid protein aggregates, such as intermediate filaments and myelin sheath. We used a wide spectrum of bioinformatics tools to evaluate the prevalence of functional disorder in several related sets of proteins, such as “main proteins” and their 44 interactors, as well as all other protein identified in the Heslington brain. These analyses revealed that all five “main proteins”, half of their interactors and almost one third of the Heslington brain proteins are expected to be mostly disordered. Furthermore, most of the remaining proteins are expected to contain sizable disordered regions. This is in contrary the expected substantial (if not complete) elimination of the disordered proteins from the Heslington brain. Therefore, it seems that the intrinsic disorder of NFH, NFM, NFL, GFAP, and MBP, their interactors and many other proteins might play a crucial role in preserving the Heslington brain by forming tightly folded brain protein aggregates, in which different parts are glued together via the disorder-to-order transitions.

As the world endures the coronavirus disease 2019 (COVID-19) pandemic, conditions of 35 million vulnerable individuals struggling with substance use disorders (SUDs) worldwide have not received sufficient attention for their special health and medical needs. Many of these individuals are complicated by underlying health conditions, such as cardiovascular and lung diseases and undermined immune systems. During the pandemic, access to the healthcare systems and support groups is greatly diminished. Current research on COVID-19 has not addressed the unique challenges facing individuals with SUDs, including the heightened vulnerability and susceptibility to the disease. In this systematic review, we will discuss the pathogenesis and pathology of COVID-19, and highlight potential risk factors and complications to these individuals. We will also provide insights and considerations for COVID-19 treatment and prevention in patients with SUDs.

Background: Monk healers provide an accessible and popular service in Southeast Asia, but little is known on the substance use status of their clients. This investigation intended to assess and compare the rate and correlates of substance use disorders in two different treatment settings (monk healers=MH and primary health care=PHC) in Thailand. Methods: In a cross-sectional study, 1024 patients (591 of MH and 613 of PHC) responded to screening measures of the “World Health Organization Alcohol, Smoking, and Substance Involvement Screening Test Lite”, and two common mental disorders (major depression and generalized anxiety disorder) from November 2018 to February 2019. Logistic regression was used to estimate the determinants of any substance use disorder in the MH and PHC setting. Results: The prevalence of substance use disorder was higher in MH clients than PHC patients: any substance use disorder 11.7% (95% Confidence Interval-CI: 9.3%-14.5%) vs 5.4% (95% CI: 3.9%-7.5%), tobacco use disorder 7.6% (95% CI: 5.7%-9.9%) vs 2.5% (95% CI: 1.5%-4.0%), alcohol use disorder 10.0% (95% CI: 8.4%-13.6%) vs 4.3% (95% CI: 3.0%-6.3%), any drug use disorder 4.2% (95% CI: 2.8%-6.1%) vs 0.3% (95% CI: 0.08%-1.3%), and any past three months drug use 8.2% (95% CI: 6.2%-10.7%) vs 1.5%, 95% CI: 0.8%-2.8%). In adjusted logistic regression analysis, among MH clients, male sex (Adjusted Odds Ratio-AOR: 9.52, 95% Confidence Interval-CI: 5.06-17.92) was positively, and were married (AOR: 0.32, 95% CI: 0.16-0.61) and high social support (AOR: 0.40, 95% CI: 0.16-0.99) were negatively associated with any substance use disorder. Among PHC patients, male sex (AOR: 7.05, 95% CI: 2.99-16.63) was positively and age (AOR: 0.95, 95% CI: 0.92-0.98) was negatively associated with any substance use disorder. Conclusion: The proportion of substance use disorders among MH attendees was more than twice that of PHC attenders in Thailand, calling for collaboration in controlling substance use disorders between the two treatment systems.

Background/ObjectivesMental health and substance use disorders (MHD, SUD) affect cardiac allograft and VAD recipients and impact their quality of life and compliance. Limited research on MHDs and SUDs in transplant and MCS candidates and recipients. This study compares the incidence of MHDs and SUDs in transplant list, VAD, and post-transplant patients with that in heart failure patients. MethodsStudy cohorts were derived from the TriNetX using ICD-10 codes. Differences in incidence were examined using the log-rank test. Adults with mental health disorders before the window of time were excluded. Propensity score matching was performed using TriNetX to balance demographic and medical comorbidities. Statistical significance was set at p<0.05. All comparisons were made between propensity-matched cohorts. ResultsTransplant waitlist patients showed a statistically significant increase in the incidence of anxiety, panic disorder, adjustment disorder, depression, mood disorder, alcohol use disorder, and eating disorder. Post-transplant patients showed a statistically significant increase in the incidence of depression and opioid use compared to the heart failure population. VAD patients showed a statistically significant increase in the incidence of depression and a statistically significant decrease in panic disorder and anxiety. ConclusionsThe results pave the pathway for further investigations on prevention and coping strategies because deterioration of mental health will significantly impact compliance with medications as well as patient survival and quality of life. The use of opioids for pain management in the early postoperative period should be further investigated to assess its impact on long-term substance use and addiction. .

Abstract: Uranium is a toxic radioactive element and is usually found in the environment in hexavalent form. It has become a necessity to remove uranium, which can enter the environment in excessive amounts through nuclear industrial activities, from access waters. Melamine formaldehyde organo clay nano composite foam (MFCNCF) was prepared as a novel adsorbent by hardening with thermal treatment. Structural, crystallographic textural and surface morphological characterization of the prepared adsorbent was made by FTIR and XRD spectroscopic and SEM and HRTEM microscopic techniques. This study aims to investigate the adsorption of U(VI) from aqueous solution by MF organo clay nanocomposite and its dependence on various variables such as initial uranium concentration, adsorption time, adsorbent dosage, initial pH, and temperature. Additionally, adsorption isotherm analysis and adsorption kinetics and thermodynamics were also examined. For this purpose, the batch adsorption experiments were carried out and the equilibrium concentration of U(VI) in the aqueous solution was measured with a UV-Vis spectrophotometer at a wavelength of 433 nm, which corresponds to its maximum absorptivity. The results regarding adsorption kinetics show that 30 min is sufficient to reach adsorption equilibrium and the data show a high fit to the pseudo-second-order kinetic model. Isotherm analysis also revealed a high fit of the data to the Type III isotherm and the Halsey model. Based on this fit, an adsorption mechanism involving two regions (electrostatic and complex formation) was proposed for the current adsorption system. The adsorption isosteric enthalpy and entropy values for the first and second regions are 3.65 and -51.02kJ/mol and 1.77 and -167.28J/mol, respectively. It was found in kmol. Experimental results showed that the prepared nanocomposite foam adsorbent is an effective and potential alternative for the effective removal of U(VI) from aqueous solutions.

Though studies have characterized lizard dung as an unconventional psychoactive substance of abuse, this has not been demonstrated in experimental settings. We evaluated the toxicity and CNS activity of lizard dung in Wistar rats. The acute and subacute toxicity studies were conducted via oral and inhalational routes. Classical models of tail suspension, forced swim, elevated plus maze, hole board, and sodium pentobarbital-induced sleeping time tests were adopted and the lizard dung were administered via both routes. No mortality was observed for all doses of the test substance administered via both routes during the toxicity studies. Significant changes in serum urea, creatinine, bilirubin, ALP, ALT and AST were recorded. Mixed inflammatory infiltrates and oedema were observed in the lungs from the group that inhaled 1.0g darkish part of lizard dung. Lizard dung produced marked reduction in the exploratory behaviour. Our findings indicate depression of the CNS.

Fear can sometimes paralyze us, and it can sometimes be exciting; for some people, fear is so crippling it can significantly mix up their lifes! We understand a little bit about how the brain acts when we are afraid, mainly by studying the brains of animals. Recently, surprising findings were made using a humble animal, the zebrafish – a small aquarium fish that in the past has helped scientists figure out how our organs develop. Zebrafish are useful because they develop quickly, reproduce richly, and have brains which are similar to ours. They also produce what we call an “alarm substance” that alerts shoalmates when one of them has been injured; when they smell this substance in the water they act as if they are very scared. When this happens, they release serotonin in their brains, a neurotransmitter that acts as a light switch, making them less afraid but more cautious – as if trying to figure out if a predator is there or not. Hopefully, finding more about how the zebrafish brains process this serotonin signal can help scientists develop better treatments for mental disorders that are associated with fear.

Transgender youth experience elevated levels of victimization and may therefore report greater drug use than their cisgender peers, yet little is known about protective factors like school belonging that may mediate this relationship. Further, scant research has explored the experiences of youth at the intersection of transgender identity and youth of color status or low socioeconomic status, especially with respect to these multiple minority statuses’ associations with peer victimization, drug use, and school belonging. Using data from the California Healthy Kids Survey, the current study employs structural equation modeling to explore the relationships among school belonging, peer victimization, and drug use for transgender youth. Findings indicate that school belonging does mediate the pathway between peer victimization and drug use for transgender youth and that although youth of color experience greater victimization, they do not engage in greater drug use than their white transgender peers. Based on these results, those concerned with the healthy futures of transgender youth should advocate for more open and affirming school climates that engender a sense of belonging and treat transgender youth with dignity and fairness.

Background and Aims: Paramedics attend an unprecedented number of drug poisoning events daily in British Columbia (BC), Canada due to the ongoing public health crisis related to an increasingly toxic and unregulated supply of illicit drugs. Paramedics have the potential to support alternative models of care to reduce harm, but their perspectives towards harm reduction initiatives are polarized. Understanding the drug-related substance use content in paramedic curriculum documents is important for deploying effective harm mitigating programs. The objective of this study was to understand what drug-related substance use content currently exists within paramedic curriculum documents in British Columbia. Methods: We performed a document analysis of curriculum documents in BC’s paramedic training institutions, the primary program textbook, and the 2011 National Occupational Competency Profile (NOCP). We used the Checklist for Assessment and Reporting of Document Analysis (CARDA) tool to perform our analysis. We analysed and coded documents both inductively and deductively and subsequently combined, refined, and used the codes to inform the development of themes via reflexive thematic analysis. Results: Of the 44 documents analysed, 22 included codes relevant to the research questions. Paramedics are primarily taught to care for people who use drugs in an acute drug-poisoning response only, with little consideration of holistic care, and no meaningful mention of harm reduction. Some stigmatizing language was found within the content. Conclusions: Many opportunities to introduce holistic models of care for people who use drugs along the entire continuum of care are unaddressed by paramedic curriculum documents in BC. Curriculum developers should include people who have lived and living experience of drug use in the co-design of educational programs involving their care. Further qualitative analyses are required to evaluate the relationship between paramedic education and provider-based stigma.

Registration of the flow pattern fine structure and the matter distribution of a free falling liquid drop in a target fluid at rest in the impact mode of coalescence, when the kinetic energy of the drop exceeds its available potential surface energy (APSE), was carried out by photo and video recording. The main attention was paid to the study of the flow structure at the initial stage of the cavity formation. To carry out color registration, the flow pattern was illuminated by several matrix LED and fiber optic sources of constant light. The planning of experiments and interpretation of the results were based on the properties of the complete solutions of the fundamental equations of fluid mechanics system, including the transfer and conversion of energy processes. Complete solutions of the system of equations describe large-scale flow components that are waves or vortices as well as thin jets (ligaments, filaments, fibers, trickles). In experiments, the jets are accelerated by the converted available potential surface energy (APSE) when the free surfaces of merging fluids were eliminated. The experiments were performed with the coalescence of water, solutions of alizarin ink, potassium permanganate, copper sulphate or iron sulphate drops in deep water. In all cases, at the initial contact, the drop begins to lose its continuity and breaks up into a thin veil and jets, the velocity of which exceeds the drop contact velocity. Small droplets, the size of which grows with time, are thrown into the air from spikes at the jet tops. On the surface of the liquid, the fine jets leave colored traces that form linear and reticular structures. Part of the jets penetrating through the bottom and wall of the cavity forms an intermediate covering layer. The forming layer jets are separated by interfaces of the target fluid. The processes of molecular diffusion equalize the density differences and form an intermediate layer with sharp boundaries in the target fluid. All noted structural features of the flow are also visualized when a fresh water drop isothermally spreads in the same tap water. The fast-changing and finely structured diffuse boundary of merging fluids, which at the initial stage has a complex and irregular shape, is gradually smoothed out by molecular diffusion processes. The similar flow patterns were observed in all performed experiments, however the geometric features of the flow depend on the individual thermodynamic and kinetic parameters of the contacting fluids.

There is a significant overlap between HIV infection and substance use disorders. Dopamine (DA) is the most abundantly upregulated neurotransmitter in Methamphetamine abuse, with receptors (DRD1-5) that are expressed by neurons as well as by a large diversity of cell types, including innate immune cells that are targets of HIV infection, making them responsive to the hyperdopaminergic environment that is characteristic of stimulant drugs. Therefore, the presence of high levels of dopamine may affect the pathogenesis of HIV, particularly in the brain. The stimulation of HIV-latently infected U1 promonocytes with DA significantly increased viral p24 levels in the supernatant at 24 hrs, suggesting effects on activation and replication. Using selective agonists to different DRDs, we found that DRD1 played a major role in activating viral transcription, followed by DRD4, which increased p24 with a slower kinetic. Transcriptome and systems biology analyses led to the identification of a cluster of genes responsive to DA, where S100A8 and S100A9 were most significantly correlated with the early increase of p24 levels following DA stimulation. Conversely, DA increased the expression of these genes’ transcripts at the protein level, respectively MRP8 and MRP14, which form a complex also known as Calprotectin. Interestingly, MRP8/14 was able to stimulate HIV transcription in latent U1 cells, and this occurred via binding to the receptor for advanced glycosylation end-product (RAGE). Using selective agonists, both DRD1 and DRD4 increased MRP8/14 on the surface and in the cytoplasm, as well as secreted in the supernatants. On the other hand, while DRD1/5 did not affect the expression of RAGE, DRD4 stimulation caused its downregulation, offering a mechanistic for the delayed effect via DRD4 on p24 increase. To cross-validate MRP8/14 as a DA signature with biomarker value, we tested its expression in HIV+ Meth users’ brains and peripheral cells. MRP8/14+ cells were more frequently identified in mesolimbic areas such as basal ganglia of HIV+ Meth+ cases compared to HIV+ non-Meth users or to controls. Likewise, MRP8/14+ CD11b+ monocytes were more frequent in HIV+ Meth users, particularly in participants with detectable viral load in the CSF. Overall, our results suggest that the MRP8 and MRP14 complex may serve as a signature to distinguish subjects using addictive substances in the context of HIV, and that this may play a role in aggravating HIV pathology by promoting viral replication in people with HIV who use Meth.

Toxoplasma gondii (T. gondii) is one of the most common parasites that infect humans. The parasite exists in approximately 40 million people in the United States. Latent infections are frequently associated with tissue cysts of T. gondii in the skeletal muscle and brain tissue that can lead to mental disorders, congenital disorders, and vision dysfunction. Furthermore, self-directed violence, impulsivity, and aggression are associated with T. gondii infection. Dopamine is associated with human behavior including pleasure, aggression, memory, and substance use disorder; however, the result of the studies on the association of T. gondii infection and drugs of abuse are not well understood. The frequency of substance use may be associated with substance-induced modification of dopamine-receptor densities and basal dopaminergic activity. Likewise, T. gondii can directly or indirectly influence dopaminergic activity in infected cells. Based on this hypothesis, the current paper aimed to systematically review all published literature on the association between drugs of abuse and T. gondii infection. Systematic review of controlled studies on T. gondii infection and substance use effects in adults were searched on the electronic databases. Studies have shown that individuals infected with T. gondii display increased risky behavior, such as excessive alcohol consumption. Furthermore, it was observed that T. gondii seropositive subjects had a reduced likelihood of self-reported substance use compared to T. gondii seronegative subjects. This study confirms that SUD is a potential risk factor for behavioral and psychiatric complications associated with T. gondii infection. Ultimately T. gondii infection in the context of drug dependence and the development of SUD remain to be elucidated. Therefore, it is necessary to conduct further research characterizing the mechanisms associated with dopamine metabolism of drug dependence and withdrawal in the context of a T. gondii infection, evaluating the role of inflammation, and identifying potential drug-and-sex specific underpinnings of these associations.

This study examined the prevalence of illegal drug use in UK students and motivators behind such behaviour. Additionally, we explored possible relationships between substance use, psychosocial motivators, and psychiatric distress. N=543 students completed online measures of substance use, anxiety, depression, perceived stress, insomnia. A series of reasons behind their use were ranked based on importance. Reported cannabis, cocaine, nitrous oxide, ketamine and MDMA use were most prevalent based on lifetime, past year, and month assessments. The experience of anxiety, depression, perceived stress, and insomnia were related to increased reports of substance use. Poor self-confidence and self-medication were key motivators of illicit drug use in those presenting greater psychiatric distress. These outcomes add to the sparse body of literature concerning illicit substance use in relation to psychiatric distress amongst UK students. Furthermore, we provided novel insight into the psychosocial motivators of such use.

Abstract: (1) Background: tuberculosis presents an epidemiological trend towards inequality, especially among people in social exclusion and situations of vulnerability. To analyze territories where there is a concentration of people diagnosed with tuberculosis, in a street situation, and who make chronic use of alcohol, tobacco, and illicit drugs. We will also analyze trends in this health condition in southern Brazil; (2) Methods: Ecological study, developed in the 399 municipalities of Paraná, Southern Brazil, with all tuberculosis cases in the homeless population registered in the Information System of Notifiable Diseases between 2014 to 2018. For data analysis, we used descriptive statistics, for the time series, the Prais-Winsten autoregression method, whereas for spatial analysis, we used the Getis-Ord Gi technique*; (3) Results: in total, 560 cases were reported. We found a predominance of alcohol, smoking, and illicit drugs users, with an increasing trend in the state and clusters of spatial risk in the East health macro-region; (4) Conclusions: We observed territories with critical levels of highly vulnerable people who use psychoactive substances and are in a street situation. The results highlight the importance of incorporating public policies of social protection to these individuals and resolutive health services that receive and assist in eradicating TB.

The use of alcohol and tobacco is related to several variables which act as risk or protective factors, depending on the circumstances. The objectives of this study were to analyze the relationship between emotional intelligence, resilience and family functioning in adolescent use of alcohol and tobacco and to find emotional profiles for their use considering self-concept. The sample was made up of 317 high school students aged 13 to 18 who filled out the Brief Emotional Intelligence Inventory, the Resilience Scale for Adolescents, the APGAR Scale, the Alcohol Expectancy Questionnaire - Adolescents and the Five-Factor Self-Concept Questionnaire. The results revealed that emotional intelligence and resilience, specifically, stress management and family cohesion were significant in the group of nonusers. Family functioning acts as a predictor factor for onset of use of tobacco and alcohol. Positive expectancies about drinking alcohol were found to be a risk factor and the intrapersonal factor to be protective. Both stress management and family cohesion were protective factors against smoking. Furthermore, cluster analysis revealed emotional profiles for users of both substances based on self-concept. Finally, the importance of the direction of the relationship between the variables studied for intervention in this problem should be mentioned. Responsible use by improving adolescent decision-making is one of the results expected from this type of intervention.

Background: Exercise is increasingly understood as an important resource for people with harmful substance use, including those in prison. Little is known about how inmates adopt various health behaviors during incarceration, without interventions. Methods: This study analyzed self-reports from 1468 inmates in Norwegian prisons, compared them according to harmful substance use pre-incarceration, and explored changes in exercise and nicotine use during incarceration. Results were presented in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. Results: Inmates with harmful substance use reported higher rates of smoking, smokeless tobacco, and physical inactivity pre-incarceration than inmates without harmful use. However, inmates with harmful use also exhibited more behavioral changes: they adopted exercise, ceased smoking, and adopted smokeless tobacco at higher rates during incarceration than the non-harmful group. Conclusions: Exercise is being taken up by a significant proportion of inmates, and may in particular be a replacement behavior for substance use. However, unhealthy behaviors are also begun or maintained. If prisons were used as an arena to facilitate healthy behaviors, the public health benefits to a marginalized group such as substance-using inmates could be substantial.

Chemical communication of predation risk has evolved multiple times in fish species, with the conspecific alarm substance (CAS) contemporaneously being the most well understood mechanism. CAS is released after epithelial damage, usually when prey fish is captured by a predator, and elicits neurobehavioral adjustments in conspecifics which increase the probability of avoiding predation. As such, CAS is a partial predator stimulus, eliciting risk assessment-like and avoidance behaviors, and disrupting the predator sequence. The present paper reviews the distribution and putative composition of CAS in fish, and presents a model for the neural processing of these structures by the olfactory and the brain aversive systems. Applications of CAS in the behavioral neurosciences and neuropharmacology are also presented, exploiting the potential of model fish (e.g., zebrafish, guppies, minnows) on neurobehavioral research.

Exercise induced bronchoconstriction (EIB) is a common complication of athletes and individuals who exercise regularly. It is estimated that about 90% of patients with underlying asthma experience EIB. Sex differences in the prevalence of asthma have been widely reported, with higher rates in boys vs. girls before puberty, and higher rates in women than men after puberty. Because atopy has been reported to occur at higher rates in athletes than in non-athletes, in this study we investigated sex differences in EIB and atopy in athletes. A systematic literature review identified 60 studies evaluating EIB and/or atopy in post-pubertal adult athletes (n=7501). Collectively, these studies reported: 1) a 23% prevalence of EIB in athletes; 2) a higher prevalence of atopy in male athletes vs. females; 3) a higher prevalence of atopy in athletes with EIB; and 4) a significantly higher rate of atopic EIB in male vs. female athletes. Our analysis indicates that the physiological changes that occur during exercise may differentially affect male and female athletes, and suggest an interaction between male sex, exercise, and atopic status in the course of EIB. Understanding these sex differences is important to provide personalized management plans to athletes with underlying asthma and/or atopy.

Nonmedical prescription stimulant use (NPSU) is an ongoing public health crisis in the United States. There exists, however, a dearth of research investigating specific childhood risk factors that may contribute to this illicit use. Adverse childhood experi-ences (ACEs) may be a significant risk factor to address in the prevention and treatment of NPSU, as research has provided evi-dence for increased substance use, potentially including prescription stimulant misuse, among individuals who have experienced trauma. A systematic review of the literature was conducted to gather and synthesize research articles specifically examining the relationship between nonmedical prescription stimulant use in adults and the experience of adverse childhood experiences (ACEs). Four studies met all inclusion criteria and were included in the review. The results demonstrated that nonmedical use of prescription stimulants in adults is significantly associated with ACEs, with a higher numerical count of ACEs associated with a greater likelihood of nonmedical prescription stimulant use. Gaps in the literature were identified, specifically noting a lack of information available regarding the relationship between ACEs and NPSU within gender- and racially-diverse populations. The findings have implications for informing interventions related to ACEs and the misuse of prescription stimulant medication in adults.

Seeds stored for a prolonged period are subject to aging and reduction in germination potential (GP), which will negatively affect seed sales. Rare-earth elements have a synergistic effect on the improvement of seed GP. In this study, we examined the effects of neodymium on biochemical components, the antioxidant protective system, and metabolism-related enzymes during germination of naturally and artificially aged seeds of three wheat cultivars. Seed germination indices, biochemical substance contents, and enzyme activities decreased after seed aging. Soaking seeds in neodymium nitrate solution revived aged wheat seeds at an optimal concentration of 20 µmol/L for 8 h. Soaking in neodymium nitrate solution increased the GP (by 2.25%–60.9%), germination index (by 1.69%–29.2%), and vigor index (by 3.36%–18.7%) of aged seeds. Compared with non-soaked seeds, soaking significantly changed the contents of biochemical substances, and the activities of antioxidant protective enzymes and metabolic enzymes in seedlings were increased. Soaking with neodymium may revive aged seeds by regulating the synthesis of soluble sugars, soluble proteins, chlorophyll, and carotenoids, and decomposing malondialdehyde, in the germinating seed. Root dehydrogenase and amylase showed different responses to the aging modes. The differential responses of root dehydrogenase and amylase may reflect differences in the resistance of enzymes to long-term mild seed aging and short-term severe environmental aging.

To evaluate the impact of a new Substance Use Disorder (SUD) education program on medical students' representations, we selected the Substance Abuse Attitude Survey (SAAS) questionnaire, which we adapted to our curriculum and cultural context. To validate this adapted version, we conducted an exploratory factor analysis following the administration of our 29-items bSAAS questionnaire to 657 medical students in Belgium (response rate: 71,1%). 23 items correlated to 3 factors namely "Stereotypes and moralism", "Treatment optimism" and "Specialised treatment" were retained (70% of total variance explained, Cronbach's alpha= 0.80) and constituted the new questionnaire called beSAAS. The factor "Specialised treatment", stood out from previous studies which could be explained by our target population and the impact of the formal, informal, and hidden curriculum in medical education. This study highlighted certain factors influencing stereotypical representations such as age, gender, origin, and personal or professional experience with substance use. Our study allowed us to retain the beSAAS as a good questionnaire to evaluate SUD stigma and highlighted interesting findings to improve SUD training in medicine. Further studies are needed to complete its validity and reliability.

Abstract Aim: To determine the efficacy of health beliefs model –based intervention in changing the belief related to substance use among university student in Mosul city-Iraq. Design: A randomized controlled trial. Methods: A probability (simple random sample) of (N=80) undergraduate student in different specialties would be selected. The study sample will be recruited from (4) colleges in the University of Mosul's Engineering, Sciences, Medicine and Education Colleges. The sample will be randomly assigned into experimental and control groups of (40) undergraduate student for each group. Such chosen is employed of pool of topics that have the criteria contain students who have using on (Smoking, Hookah, Drug abuse and Alcohol).For during from 25of October / 2019 till 1 of February/2021. Data is analyzed using the "Statistical Package for Social Science" (SPSS) software for Windows (V:26). Results: This finding indicated that before the intervention, mean scores for all concepts of HBM, add to Motivation, Control, and behaviors intensions of students they were almost equal. However, after the intervention were significantly different in the study group, while it was not significant in the control group. Conclusion:This study concluded that designing an HBM-based study could affect students' understanding and their behaviors in the field of substance abuse. Considering the positive correlation between construct of HBM, particularly in "perceived benefits and perceived severity" related to students’ beliefs. These beliefs implied a significant correlation with each other and with the attention to the prevention of addiction.

The etiology of ‘dual harm’ (the co-occurrence of self-harm and externalized violence in the same individual) is under-researched. Risk factors have mostly been investigated for each behavior separately. We aimed to examine adversities experienced between birth and age 15 years among adolescents and young adults with histories of self-harm and violent criminality, with a specific focus on dual harm. Three nested case-control studies were delineated using national interlinked Danish registers; 58,409 cases in total aged 15-35 were identified: 28,956 with a history of violent criminality (but not self-harm), 25,826 with a history of self-harm (but not violent criminality), and 3987 with dual harm history. Each case was matched by date of birth and gender to 20 controls who had not engaged in either behavior. We estimated exposure prevalence for cases vs. controls for each of the three behavior groups, and incidence rate ratios (IRRs). Experiencing 5 or more childhood adversities was more prevalent among individuals with dual harm history (19.3%; 95% CI 18.0, 20.8%) versus self-harm (10.9%; 10.5, 11.3%) and violence (11.4%; 11.0%, 11.8%) histories. The highest IRRs for dual harm were linked with parental unemployment (5.15; 95% CI 4.71, 5.64), parental hospitalization following self-harm (4.91; 4.40, 5.48) or assault (5.90; 5.07, 6.86), and parental violent criminality (6.11; 5.57, 6.70). Growing up in environments that are characterized by poverty, violence and substance misuse, and experiencing multiple adversities in childhood, appear to be especially strongly linked with elevated dual harm risk. These novel findings indicate potential etiologic pathways to dual harm.

The co-occurrence of substance use disorders (SUDs) and psychiatric conditions, often referred to as comorbidity or concurrent disorders, presents intricate challenges in both diagnosis and treatment. This comprehensive narrative review aims to synthesize and critically evaluate the existing evi-dence surrounding the management of individuals with comorbid SUDs and psychiatric disorders. Comorbidity in these domains carries profound implications for clinical practice, research, and policymaking, emphasizing the need for a holistic understanding of the intricate dynamics that arise when these conditions coexist. This review explores recent research findings, evidence-based guidelines, and emerging trends within the field, offering valuable insights for clinicians, re-searchers, and policymakers seeking to navigate the complex terrain of comorbidity in substance use and psychiatric disorders.

This paper provides an exhaustive narrative review of third-generation antipsychotics (TGAs), focusing on aripiprazole, cariprazine, brexpiprazole, and lurasidone for managing substance-induced psychosis. It includes a comprehensive literature review to evaluate the efficacy and tolerability of these medications. The paper emphasizes the distinct challenges in treating substance-induced psychosis, which is a psychiatric condition triggered by the misuse or withdrawal of various substances, leading to symptoms like hallucinations and delusions, and is distinct from primary psychotic disorders. It underscores the potential of TGAs in addressing both psychotic symptoms and substance-related issues, while highlighting the need for more research on long-term effects and advocating for an integrated approach combining pharmacological and psychological interventions

Treatment with tumor-selective photosensitive substances, such as photodynamic therapy and photoimmunotherapy, has been reported to enable the visualization of tumor drug accumulation in real time and identify the required light irradiation dose by fluorescence imaging. However, fluorescence observation is difficult during treatments performed under gastrointestinal endoscopy because of the challenges associated with including the fluorescence filter in the camera part. To address this issue, this study developed a device that integrates a narrow camera and a laser diffuser to enable fluorescence imaging through a forceps port. This device was employed to demonstrate that a laser diffuser with an NIR fluorescence imaging sensor could be delivered through a 3.2-mm-diameter port. In addition, fluorescence images of Cetuximab-IR700 were successfully observed in two mice, and the fluorescence intensity confirmed that the fluorescence decayed within 330 s. This device is expected to have practical application as a tool to identify the optimal irradiation dose for tumor-selective photosensitive substances under endoscopy.

In recent years, numerous approaches have been developed to comprehend the molecular altera-tions underlying thyroid cancer (TC) oncogenesis and explore novel therapeutic strategies for TC. It is now well established that the neurokinin-1 receptor (NK-1R) is overexpressed in cancer cells and that NK-1R is essential for viability of cancer cells. The binding of substance P (SP) to NK-1R in neoplastic cells plays a pivotal role in cancer progression by promoting neoplastic cell growth, protecting tumour cells from apoptosis, triggering invasion and metastasis through enhanced migration of cancer cells, and stimulating endothelial cell proliferation for tumour angiogenesis. Remarkably, all types of human TC (papillary, follicular, medullary, anaplastic), as well as met-astatic lesions, exhibit overexpression of SP and NK-1R compared to the normal thyroid gland. TC cells synthesize and release SP, which exerts its multiple functions through autocrine, para-crine, intracrine, and neuroendocrine processes, including the regulation of tumour burden. Con-sequently, the secretion of SP from TC results in increased SP levels in plasma, which are signifi-cantly higher in TC patients compared to controls. Additionally, NK-1R antagonists have demonstrated a dose-dependent antitumour action. They impair cancer cell proliferation on one side and induce apoptosis of tumour cells on the other side. Furthermore, it has been demonstrat-ed that NK-1R antagonists inhibit neoplastic cell migration, thereby impairing both invasiveness and metastatic abilities, as well as angiogenesis. Given the consistent overexpression of NK-1R in all types of TC, targeting this receptor represents a promising therapeutic approach for TC. Therefore, NK-1R antagonists, such as the drug aprepitant, may represent novel drugs for TC treatment.

The outbreak of COVID-19 has had a major impact on people’s daily life. This study aimed to examine use of alcohol and addictive drugs during the COVID-19 outbreak and examine their association with mental health problems and problems related to the pandemic. A sample of 4527 persons responded to the survey. Use of alcohol and addictive drugs were cross-tabulated with sociodemographic variables, mental health problems and problems related to COVID-19. Logistic regression analyses were used to examine the strength of the associations. Daily use of alcohol was associated with depression and expecting financial loss in relation to the COVID-19 outbreak. Use of cannabis was associated with expecting financial loss in relation to COVID-19. Use of sedatives was associated with anxiety, depression, and insomnia. Use of painkillers was associated with insomnia and self-reported risk of complications if contracting the coronavirus. We conclude that the occurrence of mental health problems is more important for an understanding of the use of alcohol and addictive drugs during the COVID-19 outbreak compared to specific pandemic-related worries.

During choriogenesis in insects, chorion (eggshell) is formed by surrounding follicular epithelial cells in ovarioles. However, the regulatory endocrine factor(s) activating choriogenesis and the chemical components on eggshell deserve further exploration. In two representative Coleopterans, a Coccinellid Henosepilachna vigintioctopunctata and a Chrysomelid Leptinotarsa decemlineata, genes encoding the 20-hydroxyecdysone (20E) receptor heterodimer, ecdysone receptor (EcR) and ultraspiracle (USP), and two chitin biosynthesis enzymes UDP-N-acetylglucosamine pyrophosphorylase (UAP) and chitin synthase (ChS1), were highly expressed in ovaries of the young females. RNA interference (RNAi)-aided knockdown of either HvEcR or Hvusp in H. vigintioctopunctata inhibited oviposition, suppressed the expression of HvChS1, and lessened the positive signal of Calcofluor staining on the chorions, which suggests the reduction of a chitin-like substance (CLS) deposited on eggshells. Similarly, RNAi of LdEcR or Ldusp in L. decemlineata constrained oviposition, decreased the expression of LdUAP1 and LdChS1, and declined CLS contents in the resultant ovaries. Knockdown of LdUAP1 or LdChS1 caused similar defective phenotypes, i.e., reduced oviposition and CLS contents in the L. decemlineata ovaries. These results, for the first time, indicate that 20E signaling activates choriogenesis in two Coleopteran species. Moreover, our findings propose the deposition of a CLS on the chorions.

This paper explores the multifaceted impact of biofilms, bacterial communities enveloped in extracellular polymeric substance (EPS). Biofilms play a dual role, acting as environmental champions and health threats. They interact with heavy metals, either causing pollution or aiding environmental remediation. Beneficial biofilms generate electricity and repair concrete cracks, offering sustainable solutions. Conversely, they contribute to infections, posing health risks. The study emphasizes the need for in-depth research, utilizing bibliographic methods to analyze global biofilm research. By identifying keywords, core countries, and pivotal organizations, the paper informs future investigations, offering insights into biofilm research evolution and practical applications.

The construction industry is notable contributors to atmospheric dust particulate emissions. The particulate matter (PM) produced in construction processes contains a range of chemically hazardous substances, posing significant health risks (HR) to individuals. The occupational health hazards research in construction has become a focal point of interest internationally. Initiated in the early 2000s, there has been a growing demand within the construction research community for the creation of a unified PM database that encapsulates a wide array of construction activities. Previous studies have endeavored to establish a PM database for various construction contexts, yet they have fallen short in thoroughly addressing the diversity of construction materials and the levels of toxic substances (TS) within the PM. This study validates the proof of value that HR associated with construction processes can be measured using PM and TS datasets generated from various work processes using a variety of construction materials. This was accomplished through a semi-automated Building Information Modeling (BIM)-based plugin, which streamlines the assessment of occupational HR in construction projects alongside ongoing work processes. To validate the practicality of the Health Risk Index (HRI) determination via this BIM plugin, a case study on a real renovation project was executed. This system provides construction supervisors with a tool to visually assess the HR of daily operations, thereby facilitating the adoption of preemptive measures to protect the health of construction workers.

Aldehydes are natural volatile aroma compounds generated by the Maillard reaction of sugars and amino acids in food and affect the flavor of food. They have been reported to exert taste-modifying effects, such as increases in taste intensity at concentrations below the odor detection threshold. The present study examined the taste-enhancing effects of short-chain aliphatic aldehydes, such as isovaleraldehyde (IVAH) and 2-methylbutyraldehyde, attempted to identify the taste receptors involved. The results obtained revealed that IVAH enhanced the taste intensity of taste solutions even under the condition of olfactory deprivation by a noseclip. Furthermore, IVAH activated the calcium-sensing receptor CaSR in vitro. Receptor assays on aldehyde analogues showed that C3-C6 aliphatic aldehydes and methional, a C4 sulfur aldehyde, activated CaSR. These aldehydes functioned as a positive allosteric modulator for CaSR. The relationship between the activation of CaSR and taste-modifying effects was investigated by a sensory evaluation. Taste-modifying effects were found to be dependent on the activation state of CaSR. Collectively, these results suggest that short-chain aliphatic aldehydes function as taste modulators that modify sensations by activating orally expressed CaSR. We propose that volatile aroma aldehydes may also partially contribute to the taste-modifying effect via the same molecular mechanism as kokumi substances.

Background: When homeostasis is disturbed it can occur a pathological event named inflammation. The main drugs used in the treatment consist of the non-steroidal and steroidal anti-inflammatory drugs. However, the side effects remain an obstacle during the treatments. In this work we aimed to evaluate three new regioisomers analogues of naphthyl-N-acylhydrazone derivatives. Methods: Acute models of inflammation in vivo (formalin-induced licking and carrageenan-induced inflammation) as well as in vitro were used to evaluate the effects of LASSBio-2039, LASSBio-2040, and LASSBio-2041. Results: All three substances (at 1, 10 or 30 µmol/kg) presented significant effect in the in vivo model reducing leukocyte migration, nitric oxide (NO) and interleukin-1β production. It was observed that only LASSBio-2039 significantly reduced cell migration in vitro. None of the LASSBios did affect inducible nitric oxide synthase activity nor presented NO scavenger effect. It was not observed any toxic effect neither in vivo nor in vitro. The new regioisomers analogues of naphthyl-N-acylhydrazone derivatives presented a significant anti-inflammatory activity suggesting LASSBio-2039 with a direct effect in leukocytes migratory capacity. Conclusions: Taken together the data indicate that these substances present promising effect for de development a prototype for new drugs.

Organ transplantation centers set criteria for candidate qualification, which has led to disparate healthcare resource allocation practices affecting those with a substance use history. These individuals are denied organ transplants by committees and healthcare providers who assign them lower priority status. The lower priority argument claims that healthcare resources should not be provided equally to individuals failing to share responsibility for not doing enough in addressing the diseases associated with substance use. The purpose of this work is to explore the interrelatedness between the ethics of a merit-based system of moral responsibility and lower priority setting involved in healthcare resource allocation pertaining to those with substance use histories. An integral approach to the argument against the lower prioritists with a focus on the relationship between different organ allocation practices affecting substance users and the justification for resource allocation practices in healthcare and transplant committees. Lower priority setting is challenged, and an argument offered in which substance users are assigned higher priority when relying on “doing enough” in a merit-based system of moral responsibility. It is determined that one cannot substantiate assigning a lower priority status since a lack of success in rehab does not imply a lack of effort. Additionally, neither to confirmatory behavior, nor to non-conforming behavior may freedom be justifiably ascribed in a merit-based system of responsibility because freedom to choose can neither be established a priori, nor a posteriori with respect to meritorious behavior.

Abstract: High-dose-rate interstitial brachytherapy (HDR-ISBT) has recently come to be considered one of the most effective treatments for oral cancer. On the other hand, it is important to note that radiation therapy has some side effects. Especially, radiation-induced malignancy is probably the most serious complication affecting long-term survivors. We report a case of a radiation-induced undifferentiated spindle cell sarcoma that developed following HDR-ISBT for tongue squamous cell carcinoma (SCC). A 39-year-old woman with right tongue SCC underwent HDR-ISBT (60 Gy, 10 fractions, 8 days) treatment. Five years and one month later, a tumor had developed at the primary site. Surgery was performed for the tumor, which was histopathologically diagnosed as an undifferentiated spindle cell sarcoma. That was distinct from the squamous cell origin of the primary cancer. According to recently established criteria for radiation-induced malignancy, this case was classified as a radiation-induced sarcoma. A search of the literature revealed no previous report of radiation-induced malignancy following HDR-ISBT for tongue cancer.

Novel severe acute respiratory syndrome coronavirus 2 infection (SARS-Cov-2) is an acute respiratory and infectious disease. This perspective aims to provide the basic understanding of the inflammation caused by SARS-Cov-2 and relation to trigeminal ganglion (TG). Virus enters through the mucous membranes of orofacial region and reach the TG where it resides and take control of its peptides including Substance P (SP).SP is the main neuropeptide, neuromodulator and neuro-hormone of TG, associated with nociception and inflammation under noxious stimulus. SP release is triggered and consequently, it affects the immune cells, blood vessels to release the mediators for inflammation. Cytokine storming is initiated and cause respiratory distress, bronchoconstriction and death in complicated cases. Neurokinin-1 Receptor (NK-1R) antagonist and glucocorticoids may be used to alleviate the symptoms and treat this infection. SP is the main culprit seem to be involved in the triggering of inflammatory pathways in SARS-Cov-2 infection. It has direct association with cardiorespiratory rhythm, sleep-wake cycle, nociception, ventilator responses and regulates many important physiological and pathological roles. Its over-secretion should be blocked by NK-1R antagonist. However, experimental work leading to clinical trials are mandatory for further confirmation.

Acute myeloid leukemia (AML) is an incurable hematological malignancy. To treat the disease successfully, new therapeutic strategies are urgently needed. One of these strategies can be the use of neurokinin-1 receptor (NK-1R) antagonists (e.g., aprepitant), because the substance P (SP)/NK-1R system is involved in cancer progression, including AML. AML patients show an up-regulation of the NK-1R mRNA expression; human AML cell lines show immunoreactivity for both SP and the NK-1R (it is overexpressed: the truncated isoform is more expressed than the full-length form) and, via this receptor, SP and NK-1R antagonists (aprepitant, in a concentration-dependent manner) respectively exert a proliferative action or an antileukemic effect (apoptotic mechanisms are triggered by promoting oxidative stress via mitochondrial Ca++ overload). Aprepitant inhibits the formation of AML cell colonies and, in combination with chemotherapeutic drugs, is more effective in inducing cytotoxic effects and AML cell growth blockade. NK-1R antagonists also exert an antinociceptive effect in myeloid leukemia-induced bone pain. The antitumor effect of aprepitant is diminished when the NF-κB pathway is overactivated and the damage induced by aprepitant in cancer cells is higher than that exerted in non-cancer cells. Thus, the SP/NK-1R system is involved in AML and aprepitant is a promising antitumor strategy against this hematological malignancy. In this review, the involvement of this system in solid and non-solid tumors (in particular in AML) is up-dated and the use of aprepitant as an anti-leukemic strategy for the treatment of AML is also mentioned (a dose of aprepitant (> 20 mg/kg/day) for a period of time according to the response to treatment is suggested).

Drug induced liver injury (DILI) is the most common cause of acute liver failure and 5-10% of patients hospitalized for jaundice are diagnosed with DILI. For a diagnosis of DILI to be made, there should be exclusion of other etiologies of liver injury and the use of a precipitator drug, latency of symptoms, and resolution of liver injury once the offending drug is identified and discontinued. In our case report, we present a patient with idiosyncratic hepatocellular pattern DILI after two doses of ocrelizumab for treatment of multiple sclerosis. Ocrelizumab was given 16 and 27 days prior to the onset of icterus, jaundice, and fatigue, in a patient without the evidence of prior exposure to hepatitis B virus. At presentation labs revealed severe acute hepatocellular liver injury with R factor of 30.42, marked hyperbilirubinemia, and transient hypoalbuminemia. No evidence of latent or active hepatitis B infection was detected. Drug dechallenge led to return of liver chemistries to near-normal levels 31 days after the onset of her symptoms. This case indicates DILI diagnosis associated with the use of ocrelizumab, and warrants careful monitoring of liver functions in patients even in the absence of hepatitis B.

In resettlement planning literature, much has been written on economic, land valuation and compensation, infrastructure and services aspects of the land. Psychological risks and stresses of resettled communities, however, have been under-researched. The current research looks at the psychological risks of resettlers in a Development-Induced Displacement and Resettlement (DIDR) project in Sri Lanka. Focusing on the stages of resettlement planning process discussed by Scudder and Colson four-stage model (1980) and the psychological risks discussed by Cernea’s (1990) impoverishment risks and reconstruction (IRR) model. This study evaluates the significant level of the psychological risks faced by the communities in DIDR projects in Sri Lanka relating to before and after resettlement. Moragahakanda Resettlement Project (MRP) was selected as the case study which is located in Naula DS division of Matale District, Central Province, Sri Lanka. A questionnaire survey, documents and field observations were used to evaluate the current psychological risks. The responses received from multiple choice questions were analyzed by Significant Point (SP) index. The research findings point that there are no conspicuous changes of psychological risks related to before/after resettlement has occurred in re-settlers. The findings highlight that the psychological risk levels in transition stage have remained the same level in the potential development stage. This research provides a systematic guidance enabling the physical planners to prioritize the most significant psychological risks which should be considered in the decision-making process of DIDR projects.

Background: The morbidity of myocardial infarction is keeping raise in this decade. Because of high safety and operability , percutaneous coronary intervention(PCI) has been used to conquer this disease for more than 20 years.An important complication of PCI is contrast induced nephropathy(CIN), which raises our attention. Previously, we started a study to explore the correlation between acute kidney injury and myonecrosis after scheduled percutaneous coronary intervention. Our study showed that the rate of CI-AKI in patients with post-procedural myocardial injury and undergoing elective PCI was higher than that in patients free of injury. Methods: In this study,forty male rats were randomly divided into four groups: control group (n=8), CM group (n=12), AMI group (n=8) and AMI+CM group (n=12), then velocity of renal artery blood flow (VRABF), computer tomography (CT), serum creatinine(Scr), reactive oxidative species (ROS), periodic acid-Schiff (PAS) and TUNEL were used to estimate the injury of kidney. We analyzed 327 non-ST-segment elevation acute coronary syndrome subjects undertaking elective PCI. Serum levels of creatinine (SCr) and the eGFR before coronary angiography, and 24–72 h after contrast administration were recorded to assess the renal function. Results: The data showed that VRABF was lower in AMI+CM group than CM group from 0 minute to 24h and CT number in cortex was higher in AMI+CM group than CM group at 4-hour. As well as the level of Scr in AMI+CM group displayed a significantly increase at 24-hour compared with CM group. The histopathologic scores and percentage of tubular cell apoptosis were higher in AMI+CM group at 24-hour. In 327 patients, we found that CI-AKI occurred more often in subjects with post-procedural myonecrosis (PMN) than in those without PMN (20.8% versus 5.8%, respectively, P=0.001). Conclusion: Compared to the elective patient, the injury of CIN exhibited a higher severity in AMI patient.

The tension cable-supported power transmission structure (TC-PTS) is a new type of power transmission structure suitable for mountainous terrain, which is sensitive to wind load. In this regard, a nonlinear finite element analysis model of wind-induced vibration is proposed for the TC-PTS, and the wind-induced vibration response of the structure is analyzed. Firstly, the tangent stiffness matrix of the three-dimensional truss element for the supporting suspension cable and transmission line, considering the geometric nonlinearity of structures, is derived through the relationship between the element elastic energy and its displacement. Subsequently, the element mass matrix and damping matrix of the supporting suspension cable and transmission line, as well as the element nodal load vector obtained from wind load equivalence are given. Then, based on the nonlinear finite element theory, the nonlinear dynamic equation of wind-induced vibration is established for the TC-PTS and solved by Newmark-β method combined with Newton-Raphson iterative method. Furthermore, the rain-flow counting method and Miner's linear fatigue cumulative damage theory were used for wind induced fatigue damage assessment. Finally, a two-span TC-PTS is selected as an example, and the wind-induced nonlinear vibration and fatigue damage assessment are analyzed through the proposed model. The results show that the proposed model has high computational accuracy and efficiency. With the increase of wind speed and wind direction angle, the maximum lateral displacement and tension of the supporting suspension cable and transmission line increase, and their degree of increase shows a nonlinear trend. In terms of the wind-induced fatigue analysis results of TC-PTS, the fatigue damage at the end of the supporting-conductor suspension cable is greater than the fatigue damage at its midpoint. Compared to the fatigue damage at the midpoint of the conductor, the fatigue damage at the end of the conductor is less affected by wind direction angle, and both are more significantly affected by the wind speed.

This paper presents Mathematical Formulation for Neutrino-Fission of a heavy nuclei in Neutrino-environments. It has been proposed that neutrino fission is a dynamic two-process reaction, where more than one neutrino can be captured by target nucleus. A quantity named Neutrino-Zeta with units of eV^-1 has been defined to represent Neutrino-environments. Neutrino-zeta with assumed excited energy states for heavy nuclei A∼230-270 is estimated to be 0.0212 MeV^-1, with the probability of fission Barrier energy state P(E_x,f)= 0.169064014 with E_x,f =6MeV. P(E_x,f)=0.222664 is highest at zeta=0.1MeV^-1 . It has been shown that probabilities of certain excitation energy states and their corresponding decay reactions at those excitation energies can be equal for two neutrino-zetas. Neutron induced fission for different neutrinos hypothesize that probability of symmetric fission channels is higher at low neutrino-zetas, which can be tested experimentally.

Neurokinin-1 receptor (NK-1R) antagonists exert an antitumor action, are safe and do not cause serious side-effects. These antagonists (via the NK-1R) exerted multiple actions against cancer: antiproliferative and anti-Warburg effects, apoptosis, anti-angiogenic and antimetastatic. These multiple effects have been shown in a broad-spectrum of cancers. The drug aprepitant (an NK-1R antagonist) is currently used in clinical practice as antiemetic. In in vivo and in vitro studies, aprepitant also showed the aforementioned multiple antitumor actions against many types of cancer. A successful combination therapy (aprepitant and radiotherapy) has recently been reported in a patient suffering from lung carcinoma: the tumor mass disappeared and side-effects were not observed. Aprepitant could be considered as an intelligent bullet against cancer. The administration of aprepitant in cancer patients to prevent recurrence and metastasis after surgical procedures, thrombosis and thromboembolism is discussed as well as the possible link, through the SP/NK-1R system, between cancer and depression. Our main aim is to review the multiple antitumor actions exerted by aprepitant and the use of this drug is suggested in cancer patients. Altogether, the data support the reprofiling of aprepitant for a new therapeutic use as an antitumor agent.

Spatially resolved, line-of-sight measurements of aluminum monoxide emission spectra in laser ablation plasma are used with Abel inversion techniques to extract radial plasma temperatures. Contour mapping of the radially deconvolved signal intensity shows a ring of AlO formation near the plasma boundary with the ambient atmosphere. Simulations of the molecular spectra were coupled with the line profile fitting routines. Temperature results are presented with simultaneous inferences from lateral, asymmetric radial, and symmetric radial AlO spectral intensity profiles. This analysis indicates that we measured shockwave phenomena in the radial profiles, including a temperature drop behind the blast wave created during plasma initiation.

Biomimetic design has recently received widespread attention. Inspired by the Terebridae structure, this paper provides a structural form for suppressing vortex-induced vibration (VIV) response. Four different structural forms are shown, including the traditional smooth cylinder (P0), the Terebridae-inspired cylinder with a helical angle of 30° (P30), the Terebridae-inspired cylinder with a helical angle of 60° (P60), and the Terebridae-inspired cylinder with a helical angle of 90° (P90). And computational fluid dynamics (CFD) method is adopted to solve the flow pass the Terebridae-inspired structures, and the vibration equation is solved using the Newmark-β method. The results show that the VIV responses are effectively controlled in the lock-in region for P30, P60, and P90, and P60 shows the best VIV suppression performance. The transverse amplitude and the downstream amplitude can be reduced by 82.67% and 91.43% respectively for P60 compared with that for P0, and the peak of the mean-drag coefficient is suppressed by 53.33%. The Q-criterion vortices of P30, P60, and P90 are destroyed, with irregular vortices shedding. It is also found that the boundary layer separation is located on the Terebridae-inspired ribs. The twisted ribs cause the separation point to constantly change along the spanwise direction, resulting in the development of the boundary layer separation being completely destroyed. The strength of the wake flow is significantly weakened for the Terebridae-inspired cylinder. In the lock-in region, the motion trajectory presents a typical 8-shaped for P0, while the motion trajectory of the Terebridae-inspired cylinder tends to be a flat 1-shaped.

Trichoderma spp. are widely used in plant disease control as biocontrol agents. Inducing plant disease resistance is an important biocontrol mechanism of Trichoderma. It is of great significance to explore the factors involved in the surface recognition and interaction of Trichoderma with plants. Hydrophobin is a small molecular protein rich in cysteine in higher filamentous fungi and has been found to participate in the morphogenesis and interaction of fungi with other organisms. In this study, the type II hydrophobic protein-coding gene Thfb6 from T. harzianum TH33 was cloned and heterologously expressed in Escherichia coli BL21 (DE3). The purified recombinant protein Thfb6 induced a hypersensitive response in tobacco leaves, a burst of reactive oxygen species, and an accumulation of callose, phenolic substances, and lignin in tobacco, indicating that Thfb6 can induce an early defense reaction in tobacco. Thfb6 also enhanced the systemic resistance of tobacco against tobacco mosaic virus. The rate of lesion number reduction by treatment with Thfb6 could be up to 36.02%. Thfb6 increased the activity of tobacco defense-related enzymes, including phenylalanine ammonia-lyase (PAL), polyphenol oxidase, and peroxidase, which were all more than three times the control after 3–5 days post treatment of Thfb6. The transcription of resistance-related genes, including the PAL gene, non-expresser of pathogenesis-related gene1 (NPR1), and basic pathogenesis-related gene 1 (PR1-b), were upregulated after Thfb6 treatment. The relative expression levels of the PAL and NPR1 genes were highest on the third and fourth days after Thfb6 treatment, at 5.5 times and 8.3 times that of the control, respectively. The relative expression level of PR1 on the sixth day after Thfb6 treatment was 5.3 times that of the control. These results indicate that the improvement of defense-related enzyme activity and the induced expression of disease-resistance-related genes were the main mechanisms by which Thfb6 induced systemic resistance in tobacco.

Fusarium wilt diseases severely influence the growth and productivity of numerous crop plants. The consortium of antagonistic rhizospheric Bacillus strains and quercetin were evaluated imperatively as a possible remedy to effectively manage the Fusarium wilt disease of tomato plants. The selection of Bacillus strains was made based on in-vitro antagonistic bioassays against Fusarium oxysporum f.sp. lycoprsici (FOL). Whereas, quercetin was selected after screening a library of phytochemicals during in-silico molecular docking analysis using tomato LysM receptor Kinases “SILKY12” based on its dual role in symbiosis and plant defense responses. After the selection of test materials, pot trials were conducted where tomato plants were provided consortium of Bacillus strains as soil drenching and quercetin as a foliar spray in different concentrations. The combined application of consortium () and quercetin (1.0 mM) reduced the Fusarium wilt disease index up to 69% also resulting in increased plant growth attributes. Likewise, the imperative application of the Bacillus consortium and quercetin (1.0 mM) significantly increased total phenolic contents and activities of the enzymes of the phenylpropanoid pathway. Non-targeted metabolomics analysis was performed to investigate the perturbation in metabolites. FOL pathogen negatively affected a range of metabolites including carbohydrates, amino acids, phenylpropanoids, and organic acids. Thereinto, combined treatment of Bacillus consortium and quercetin (1.0 mM) ameliorated the production of different metabolites in tomato plants. These findings prove the imperative use of Bacillus consortium and quercetin as an effective and sustainable remedy to manage Fusarium wilt disease of tomato plants and to promote the growth of tomato plants under pathogen stress conditions.

Land use/land cover (LULC) changes have a substantial influence on ecosystem services. The objective of this study is to estimate LULC dynamics induced ecosystem service values (ESV) changes in Western Ethiopia. Data were acquired from Landsat images of the area for four periods (1990-2020), and 221 sample households. The areas of LULC classes and the improved ESV coefficients of Costanza et al (1997) were used estimate ESV changes in 1990-2020. Forest provides diverse provisions, regulatory, supportive and cultural services. Analysis of the Landsat images showed that forest, farmland, settlement, water body and bare-land were the major LULC classes in the study area. While forest ESV had accounted 46.1% (US$ 4.95 million) of the ESV of Wayu-Tuka district in 1990, farmland ESV constituted the largest share (63.3%, US$ 5.21 million) of the ESV of the area after 30 years (2020). The ESV of forest and bare-land showed decreasing trends in three decades (1990-2020) but the farmland service value revealed an increasing trend in the same periods. Forest ecosystem exhibited the largest service value loss (US$ 3.91 million) in 1990-2020; whereas, the service value gain of farmland was only US$ 2.2 million although farmland was responsible for the conversion of the largest area size (9,766.5 ha) from other land covers in 30 years. LULC change induced net ESV loss of the district in three decades (1990-2020) was 23.4% (US$ 2.51 million). Land conversion due to expansion of farmland (by 9,766.5 ha) and settlement (by 4,061.3 ha) was the main cause for the LULC dynamics and the significant ESV loss in 1990-2020. Thus, the government and local people should cooperate so as to curb the steady degradation of forest and its ecosystem services in Wayu-Tuka district, Western Ethiopia.

A switchable and tunable terahertz (THz) metamaterial based on photosensitive silicon and Vanadium dioxide (VO2) was proposed. By using finite-difference time-domain (FDTD) method, the transmission and reflective properties of the metamaterial were investigated theoretically. The results imply that, the metamaterial can realize a dual electromagnetically induced transparency (EIT) or two narrow-band absorption depending on the temperature of the VO2. Additionally, the magnitude of the EIT and two narrow-band absorption can be tuned by varying the conductivity of photosensitive silicon (PSi) via pumping light. Correspondingly, the slow light effect accompanying the EIT can also be adjusted.

The plant immunity system is more and more revisited and new elements and roles are attributed to participate in the response to biotic stress. New terminology is also applied trying to identify different players in the whole scenario of immunity: Phytocytokines are one of those elements that are gaining more attention due the characteristics of processing and perception, and showing they are part of a big family of compounds that can amplify the immune response. This review aims to highlight the last findings about the role of phytocytokines in the whole immune response on biotic stress, including basal and adaptive immunity, and to expose the complexity in their action in plant perception and signaling events.

This study presents the developments regarding the time-domain-induced polarisation method, as a supporting tool for resistivity soundings during investigations of coastal detrital aquifers that are salinised by marine intrusion. The interpretation of resistivity measurements in such aquifers, which have variable hydrochemistry and lithology, involves uncertainties owing to the presence of low-resistivity lithologies, such as clays. To reduce these uncertainties, the use of other geophysical parameters is necessary; hence, this study focuses on induced polarisation, since it can be measured simultaneously with resistivity. In detail, we propose the determination of induced polarisation using 1D techniques, while developing a different algorithm for processing the induced polarisation data. The aim is to extend the results of this phenomenon, using instead of chargeability, the concepts of polarisability and decay time, which are extracted from the decay curve, given that they represent more intrinsic properties of the various analysed subsurface media. We present results obtained by applying this methodology to a Quaternary aquifer of the Costa del Sol in the SE Iberian Peninsula (in the province of Almería) during two different campaigns, one before and one after winter (i.e., in October and February, respectively). The results reveal the position of the saline front during each campaign, while reflecting the seasonal movement of the marine intrusion.

This paper develops the study of the effect of powerful ultrasound on the laser breakdown of liquids and a comparative study of the possibilities of acoustic and optical diagnostics of breakdown. The method of laser-induced breakdown spectroscopy (LIBS) for elemental analysis of liquids, along with high efficiency, continues to be less sensitive compared to traditional chemical methods. The paper develops a method of using additional ultrasound irradiation of the laser breakdown area in order to increase the efficiency of LIBS. Using the developed technique, spectral lines of chemical elements such as potassium, manganese, sodium, calcium, etc. were obtained for the first time depending on the frequency and power of ultrasound. It is shown that a sharp increase in the intensity of spectral lines of elements in water during laser breakdown is observed in the field of high-power ultrasound. It indicates an increase in the sensitivity of the combined method of ultrasonic LIBS. Along with the optical spectrum, the spectral and energy characteristics of acoustic emission were studied. An automated complex for hydrophysical and spectral studies is described, which was tested in the Sea of Japan during the voyage No. 81 of the research vessel RV "Professor Gagarinsky" in August 2022.

We have developed an unsteady and non-linear wind synopsis simulator called RIAM-COMPACT (Research Institute for Applied Mechanics, Kyushu University, COMputational Prediction of Airflow over Complex Terrain) in order to simulate the airflow on a microscale, i.e., a few tens of km or less. In RIAM-COMPACT, the large-eddy simulation (LES) has been adopted for turbulence modeling. LES is a technique in which the structures of relatively large eddies are directly simulated and smaller eddies are modeled using a sub-grid scale model. In the present study, we have conducted the numerical wind diagnoses for Taikoyama Wind Farm nacelle separation accident in Japan. The simulation results suggest that all six wind turbines at the Taikoyama Wind Farm are subject to significant influence from separated flow (terrain-induced turbulence) which is generated due to the topographic irregularities in the vicinity of the wind turbines. A proposal has been also made on reconstruction of the wind farm.

The official recommendations to manage COVID-19 in the outpatient setting focus on high-cost drugs (remdesivir, nirmatrelvir-ritonavir, molnupiravir), suffering from many problems. Therefore, one may consider also other treatments meeting these criteria: • promising effectiveness, based on favorable randomized controlled trials (RCTs) of sufficient validity. Even without definitive evidence, physicians and informed patients can consider them if they are also: • safe, to the state of knowledge • with a very favorable opportunity cost • biologically plausible/not implausible • accessible • without major commercial sponsors in the trials promoting them, and with researchers without major conflicts of interests. The main focus is on a limited group of functional foods and some their active ingredients, with further mention of other substances of different origin, yet fully meeting all the aforementioned criteria. The functional foods and substances described and discussed certainly do not cover all the known effective therapies for COVID-19 (in one case also for Long-COVID), but the only therapies proposed in this paper currently satisfy all the above criteria. The supporting scientific evidence will favor meta-analyses of RCTs that include the most definitive outcome: all-cause mortality, i.e. the outcome that most fully informed people tend to prioritize. Furthermore, the reported evidence favors clinical studies of the most valid design, i.e. RCTs.

In January and February 2001, El Salvador was hit by two strong earthquakes that triggered thousands of landslides, causing 1,259 fatalities and extensive damage. The analysis of aerial and SPOT-4 satellite images taken a few days after the events allowed us to map 6,491 coesismic landslides, which occurred in 14 study areas extending for about 400 km2. Four different Multivariate Adaptive Regression Splines (MARS) models were produced by using different covariate sets and landslide inventories, the latter containing the slope failures triggered by an extreme rainfall event of November 2009 and those induced by the earthquakes of 2001. Moreover, two validation scenarios were employed, including the 25% and 95% of the mapped landslides, respectively. The results of our experiment revealed that: (i) MARS algorithm provides reliable predictions of coesismic landslides; (ii) models calibrated with rainfall-induced landslides predict with acceptable accuracy landslides caused by deep earthquakes and distributed over vast areas; (iii) the best accuracy is achieved by models trained with both preparatory and trigger variables; (iv) a small portion of the landslides produced by an earthquake can be used to calibrate MARS predictive models that help to identify slopes where yet unreported landslides may have occurred.

Drug-induced liver disease represents one of the main problems in the therapeutic field. As with most pathologies, also in this case various risk factors can be recognised, such as age, sex, but also the gut microbiota. Therefore all drugs on the market can, in fact, cause hepatotoxicity of varying degrees. Drugs used in the treatment of IBD can also cause these adverse effects and even lead to DILI. In this review, the various classes of drugs used in the treatment of IBD were taken into consideration and the various adverse effects on the liver were illustrated. In particular, a major role has emerged regarding hepatotoxicity of immunosuppressants. Biological drugs, however, seem to be responsible for these complications to a much lesser extent.

Within the spectra of lanthanide atoms quite often overlapping spectral lines (blends) are observed. On the example of complicated blend situations within Pr I and La I it is shown that in such cases a combination of optogalvanic and laser-induced fluorescence detection is necessary to find all transitions contributing to the observed spectral signature.

Peptidylarginine deiminases (PADs) have an important role in the pathogenesis of generating citrullinated proteins which is one type of protein posttranslation modifications (PTMs). Additionally, peptidylarginine deiminases 4 (PAD4) is a component of neutrophil extracellular traps (NET) that leads to autoimmune disease during NETosis. Our aim was to check the PAD4 enzyme expression at level of gene and protein expression in streptozotocin (STZ) induced diabetic rat pancreas and checking the link between PAD4 and inflammatory cytokines. Wistar rats were divided into two groups: control group and diabetic STZ group. STZ was administered by intraperitoneally (60 mg/kg/ body weight). Rats were caged for six weeks and then terminated. Pancreatic tissue was harvested for measurement of PAD4 protein expression, PAD4 mRNA, citrulli-nated histone-3 protein (CITH3), cytokines and Ca2+ content. All measurements in diabetic rats were significantly in-creased compared to non-diabetic rats (p

Tongue mobility is an obstructive sleep apnoea (OSA) marker and myofunctional therapy (MFT) target. For this reason, all patients with sleep-disordered breathing should require a combined functional assessment from an ear, nose, and throat (ENT) specialist and a phonoaudiologist to confirm or rule out the presence of tongue-tie. To our knowledge, this is the first case of a 13-year-old girl diagnosed with severe OSA and a significant decrease of 94% in her apnoea index (AI), requiring frenotomy with immediate postoperative change in the tongue position. A drug-induced sleep en-doscopy (DISE) was performed before and immediately post-frenotomy, and the anatomical changes provoked by this surgery during sleep were confirmed for the first time.

Induced pluripotent stem cells (iPSC) are derived from reprogrammed adult somatic cells. These adult cells are manipulated in vitro to express genes and factors essential for acquiring and maintaining embryonic stem cell (ESC) properties. This technology is widely applied in many fields, and there has been much attention to developing iPSC-based disease models to validate drug discovery platforms and study pathophysiological molecular processes underlying disease onset. Especially in neurological diseases, there is a great need for iPSC-based technological research, as these cells can be obtained from each patient and carry the individual’s bulk of genetic mutations and properties. Moreover, iPSC can differentiate into multiple cell types. These are essential characteristics since the study of neurological diseases is affected by limited access to injured sites, in vitro models composed of various cell types, the complexity of reproducing the brain’s anatomy, ethical issues, and the fact that post-mortem cell culture is challenging. Neurodegenerative diseases enormously impact global health due to their high incidence, symptoms severity, and usually lack of effective therapies. Recently, analyses using disease-specific iPSC-based models confirmed their efficacy for testing multiple drugs. This review summarizes the advances in iPSC technology used in disease modeling and drug testing with a primary focus on neurodegenerative diseases, including Parkinson’s and Alzheimer’s diseases.

Idiosyncratic drug induced liver injury (DILI) is an unpredictable reaction of exposed individual on a certain drug, and the drug-induced autoimmune hepatitis (DIAIH) presents a DILI phenotype that mimics idiopathic autoimmune hepatitis (AIH) when considering the clinical, biochemical, serological and histological parameters. We present a case of a 48-year-old male that was hospitalized due to severe hepatocellular liver injury two months after the self-treatment with the muscle-building dietary supplement based on arginine-alpha-ketoglutarate, L-citrulline, L tyrosine, creatine malate and beet extract. His immunology panel was positive with increased IgG levels, and the radiologic methods showed no signs of chronic liver disease. He underwent corticosteroid treatment with adequate response. After the therapy withdrawal, a clinical relapse occurred. Seven months after the initial presentation liver MR suggested the initial cirrhotic changes of the right liver lobe. Liver biopsy revealed abundant lymphoplasmacytic infiltrate with piecemeal necrosis and grade 2 fibrosis. He responded well on the corticosteroid treatment again, and was further treated with low dose prednisone without additional relapses. Several years later, further management confirmed presence of liver cirrhosis with no histological or biochemical signs of the disease activity. DIAIH is a DILI phenotype difficult to distinguish from idiopathic AIH despite a wide armamentarium of diagnostic methods. Regular patient monitoring and clinical open-mindedness with the adjustment of therapeutic approaches according to the disease course are more important than strict labelling of the disease.

Background: Pteropodine (PT) is a component of some plants with potentially useful pharmaco-logical activities for humans. This compound has biomedical properties related to the modulation of the immune system, nervous system, and inflammatory processes. This study addresses the an-ti-inflammatory and antioxidant capacity of pteropodin in a murine model of arthritis and induced edema of the mouse ear. Methods: To evaluate the anti-inflammatory activity, we used the reversed passive Arthus reaction (RPAR), which includes the rat paw edema test, the rat pleurisy test, and a mouse ear edema model. The antioxidant effect was evaluated by determining the myeloperoxidase enzyme activity. Results: PT showed an anti-inflammatory effect in the different specific and non-specific tests. We found a 52 to 74% of inhibitory effect of PT in the rat paw edema test, 52% of reduction of the pleural exudate volume, and low neutrophil count (28%), when compared to the control group. We also found a 81% of inflammatory inhibition of the ear edema, and a significant myeloperoxidase enzyme inhibition by the three doses of PT. Conclusions: PT exerted a potent an-ti-inflammatory effect in the acute inflammation model in rodents.

The soil-borne pathogens, particularly Fusarium oxysporum f. sp. niveum (FON) and southern root-knot nematode (RKN, Meloidogyne incognita) are the major threat to watermelon production in the south-eastern United States. The role of soil micronutrients on induced resistance (IR) to plant diseases is well-documented in soil-based mediums. However, soil-based mediums limit the determination of the role(s) of individual micronutrients in IR. In this manuscript, we utilized hydroponics to assess the effect of controlled application of micronutrient, including iron (Fe), manganese (Mn), and zinc (Zn) on the expression of some IR genes (PR1, PR5, and NPR1 from salicylic acid (SA) pathway, and VSP, PDF, and LOX genes from jasmonic acid (JA) pathway) in watermelon seedlings upon inoculation with either FON or RKN or both. Plants were treated with higher (3X) or lower (0.5X) concentrations of micronutrients in Steiner solution (X= standard dose of micronutrient) for 7 days in a hydroponics system under greenhouse conditions. A subset of micronutrient-treated plants was inoculated (on the 8th day of micronutrient application) with FON and RKN (single and mixed). The expression of the IR genes in treated and control samples were evaluated using qRT-PCR. Although, significant phenotypic differences were not observed with respect to the severity of wilt symptoms or RKN galling with any of the micro-nutrient treatments within the 30 day-experimental-period, differences in the induction of IR genes were observed. However, the level of gene expression varied with sampling period, type and concentration of micro-nutrients ap-plied, and pathogen-inoculation. In the absence of pathogens, no significant changes were observed in the expression level of IR genes on 7th day of micronutrient treatment. However, pathogen inoculation affected the expression levels of the IR genes at 3-day post-inoculation. In FON inoculated plants, PDF was upregulated in high Fe treatment, whereas in RKN inoculated plants, low Mn treatment resulted in up-regulation of VSP. In the case of mixed inoculation with FON and RKN, the plants with low Zn treatment resulted in the upregulation of PR1. These observations suggest that the type and concentration of micronutrients in watermelon may potentially induce systemic resistance against FON and RKN through SA and JA pathways.

MiRNAs are 20-22 nucleotide long single-stranded non-coding RNA sequences, which can regulate post transcriptional activity of mRNA by binding with it at 3’UTR region (untranslated region). Thus deregulation of miRNA expression is responsible for dysregulating mRNA function which contributes in developing various diseases as well as cancerous phenotypes. Alteration of single nucleotide in miRNA sequence is one of the reasons behind deregulation of miRNA expression. The most frequent carcinoma in current day is breast cancer which causes a high mortality among women around the world as well as India. Despite of the advancement of diagnostic tools, strategies and treatment, the cases of breast cancer is increasing every year. There are plenty of biomarkers like ER, PR, Her2, Ki-67, etc available which are frequently used in diagnosis and treatment of breast cancer. After the discovery of MiRNA in 1993 in Caenorhabiditis elegans, it is attracting all the limelight in diagnosis and treatment of different carcinomas as well as breast cancer. In this review we will discuss on involvement of different types of MiRNAs and miR SNPs in breast cancer occurrence and susceptibility in a detailed manner.

The color changes corresponding to chromophore structures in lignin caused by exposure of Eucalyptus（Eucalyptus grandis and E. urophylla）to heat were investigated. Eucalyptus wood samples were heated in saturated steam atmospheres for 10 h at 110℃, 130℃, and 150℃. The lignin was isolated before and after heat treatment. The physicochemical properties of the lignin and changes in chromophore structures during heat treatment was evaluated through wet chemical analysis, FTIR, UV-Vis, GPC, XPSand 13C-NMR. The color of the wood became darker and redder with the increase in pressure and temperature. Depolymerization and dehydration reactions occurred via demethoxylation with heat treatment in saturated steam at 110℃ or 130℃. Lignin condensed to form insoluble compounds after heat treatment in saturated steam at 150℃. G units increased and S units decreased through demethylation during heat treatment, as revealed by FTIR and 13C-NMR analysis.

In the present study, field observation wind data from the time of the wind turbine blade damage accident on Shiratakiyama Wind Farm were analyzed in detail. In parallel, high-resolution LES turbulence simulations were performed in order to examine the model’s ability to numerically reproduce terrain-induced turbulence. The comparison of the observed and simulated time series (1 second average values) from a 10 minute period from the time of the accident led to the conclusion that the settings of the horizontal grid resolution and time increment are important to numerically reproduce the terrain-induced turbulence that caused the wind turbine blade damage accident on Shiratakiyama Wind Farm. A spectral analysis of the same set of observed and simulated data revealed that the simulated data reproduced the energy cascade of the actual terrain-induced turbulence well.

At the Atsumi Wind Farm in Aichi Prefecture, Japan, damage to wind turbines occurred frequently due to terrain-induced turbulence. In the present study, numerical analyses of terrain-induced turbulence were conducted by reproducing the topography in the vicinity of the wind turbine sites in high resolution and using RIAM-COMPACT natural terrain version, which is based on large eddy simulation (LES). The results of the diagnoses indicated that, in the case of south-easterly wind, terrain-induced turbulence is generated at a small terrain feature located upstream of Wind Turbine (WT) #2, which serves as the origin of the turbulence. At the Atsumi Wind Farm, a combination of the series of wind diagnoses and on-site operation experience led to a decision to adopt an "automatic shutdown program" for WTs #1 and #2. Here, "automatic shutdown program" refers to the automatic suspension of wind turbine operation upon the wind speed and direction meeting the conditions associated with significant effects of terrain-induced turbulence at a wind turbine site. The adoption of the "automatic shutdown program" has successfully resulted in a large reduction in the number of occurrences of wind turbine damage, thus, creating major positive economic effects. 1) a reduction in the repair costs by 9.322 million yen per year per wind turbine, 2) an increase in the availability factor by 8.05%, and 3) an increase in the capacity factor by 1.7%.

We use earthquake ground motion modelling via Ground Motion Prediction Equations (GMPEs) and numerical simulation of seismic waves to consider the effects of site amplification and basin resonance in Jakarta, the capital city of Indonesia. While spectral accelerations at short periods are sensitive to near-surface conditions (i.e., Vs30), our results suggest that, for basins as deep as Jakarta’s, available GMPEs cannot be relied upon to accurately estimate the effect of basin depth on ground motions at long periods (>1 s). Amplitudes at such long periods are influenced by entrapment of seismic waves in the basin, resulting in longer duration of strong ground motion, and interference between incoming and reflected waves as well as focusing at basin edges may amplify seismic waves. In order to simulate such phenomena in detail, a basin model derived from a previous study is used as a computational domain for deterministic earthquake scenario modeling in a 2-dimensional cross-section. A M_w 9.0 megathrust, a M_w 6.5 crustal thrust and a M_w 7.0 instraslab earthquake are chosen as scenario events that pose credible threats to Jakarta, and the interactions with the basin of seismic waves generated by these events were simulated. The highest PGV amplifications are recorded at sites near the middle of the basin and near its southern edge, with maximum amplifications of PGV in the horizontal component of 200% for the crustal, 600% for the megathrust and 335% for the deep intraslab earthquake scenario, respectively. We find that the levels of ground motion response spectral acceleration fall below those of the 2012 Indonesian building Codes's design response spectrum for short periods (< 1 s), but closely approach or may even exceed these levels for longer periods.

Starvation of photoreceptors induced by reduced dysregulated ocular blood flow is proposed as a common pathway for the pathogenesis of retinitis pigmentosa (RP). The current study evaluated the safety and efficacy of ophthalmic nerve stimulation (ONS) as an ocular blood flow neuromodulator, combined with ascorbic acid (AA) as a potent anti-oxidant in the treatment of RP. Additionally, the initial characteristics of rod responders were identified. Forty participants with simple, non-syndromic RP presented with a characteristic triad of RP (the bone spicule pigmentation, attenuation of retinal blood vessels, and waxy optic disc pallor), were en-rolled in a prospective open-label single-armed interventional study. The severity of the disease was clinically graded into six stages. Patients with an established diagnosis of RP; aged ≥ 4 years, with best corrected visual acuity (BCVA) ≥ 20/400 were included. All participants were daily treated with bilateral ONS sessions combined with intravenous administration of AA for two weeks. The primary efficiency endpoint was 6 months’ changes in scotopic vision as measured by a 10-item, 100-point, Low Luminance Questionnaire-10 (LLQ-10). The secondary efficiency points included best corrected visual acuity (BCVA) and contrast sensitivity. Rod responders were defined by ≥ 25 points increment of LLQ-10 score at 6 months after treatment. The results showed that ONS combined with AA treatment significantly improved low luminance vision, BCVA, and contrast sensitivity in patients with RP (p≤ 0.05). At 6-month visit, twenty-four (60%) patients were identified as rod responders and 16 (40%) patients were rod-non-responders. The mean change in LLQ-10 score was (46.35 ±16.81) in rod responders versus (4.9 ± 7.6) in non-responders (p < 0.0001). A clinically significant improvement of BCVA (≥0.2 logMAR) and contrast sensitivity (≥0.3 log unit) were demonstrated in 50% of the right eyes of rod responders. No serious adverse effects were reported and headache in 5 patients (12.5%) was the only en-countered side effect in this study. In conclusion, ocular neuromodulation is a safe therapeutic strategy for RP. It significantly improved night vision, BCVA, and contrast sensitivity. Determinants of rod responders include a shorter duration of night blindness, an earlier stage of the disease, and a relatively thicker ganglion cell layer at baseline. Additionally, two therapeutic scenarios were recognized; an early disease-modifying intervention that restores night vision and reverses the disease process and a late cone rescue intervention that improves/maintains central vision.

Background: The primary objective worldwide during the COVID-19 pandemic has been controlling disease transmission. However, lockdown measures used to mitigate transmission have affected human behavior and altered lifestyles, with a likely impact on chronic non-communicable diseases. More than a year into the pandemic, substantial peer-reviewed literature has emerged on altered lifestyles following the varying lockdown measures imposed globally to control the virus spread. Objective: To explore the impact of lockdown measures on the six lifestyle factors, namely diet, physical activity, sleep, stress, social connectedness, and the use of tobacco, alcohol, or other harmful substances.Methods: We comprehensively searched PubMed and the World Health Organization’s global literature database on COVID-19 and retrieved 649 relevant articles for the narrative review. A critical interpretative synthesis of the articles was performed.Results: Most of the articles included in the review identified the negative effect of lockdown measures on each of the lifestyle factors in many parts of the world. Interestingly, encouraging lifestyle trends were also highlighted in a few articles. Such trends can positively influence the outcome of lifestyle-related chronic diseases, such as obesity and diabetes.Conclusions: The COVID-19 pandemic provides an opportunity to better understand the negative impact of strict lockdown measures on lifestyles. At the same time, it helps us identify and initiate positive behavioral changes, which, if consolidated, could improve chronic disease outcomes. It is up to governments, communities, and healthcare/academic entities to derive benefit from lessons learned from the pandemic, with the ultimate objective of better educating and promoting healthy lifestyles among communities.

In order to summarized the polygenic background of psychiatric diseases, polygenic risk scores (PRS) have been developed. Recently, PRS have been use to predict patients with higher comorbidities in psychiatric diseases, like dual diagnosis. PRS are principally derived in analysis of Caucasian and Asian populations, we are not aware of how this PRS could be applied in populations with high admixture. In order to explored this, the present work has the aim to analyzed if previous calculated PRS for psychiatric diseases could predict dual diagnosis in Mexican population, and also, if PRS calculation could be influenced by Mexican Amerindian (MA) global ancestry. We performed PRS calculation, using PRSice, with summary genome-wide association statistics previously published for psychiatric diseases, and also, performed Nagelkerke correlation test in order to established if PRS are correlated with dual diagnosis. We found that dual diagnosis could be predicted by major depressive disorder polygenic risk score. Nevertheless, schizophrenia polygenic risk score is highly correlated with global MA ancestry, independently of the schizophrenia diagnosis. Our results reinforced the notion that PRS calculation could be deviated by the MA global ancestry, nevertheless analysis on larger sample sizes are required in order to clarified this issue.

A metastable β-Ti alloy, Ti–10V–3Fe–3Al (wt.%), was subjected to thermos-mechanical processing including the compression test at 725°C, which is below the β transus temperature (780°C), and at strain rate of 10-3s-1. The presence of phases was determined using transmission electron microscopy and X-ray diffraction. Although the dynamic recovery took place together with slip, both deformation-induced α˝ martensite and ω were detected as other operating mechanisms for the first time in metastable-β Ti alloys deformed in α+β region. The volume fraction of stress-induced α˝ was higher than that of the same alloy deformed at room temperature due to higher strain applied. Stress-induced twinning was not operational, which could be related to the priority of slip mechanism at high temperature resulted from thermally-assisted nucleation and lateral migration of kink-pairs.

The first detection of gypsum (CaSO4.2H2O) by the Mars Science Laboratory (MSL) rover Curiosity in the Gale Crater, Mars created a profound impact on planetary science and exploration. The unique capability of plasma spectroscopy involving in situ elemental analysis in extraterrestrial environments, suggesting the presence of water in the red planet based on phase characterization and providing a clue to Martian paleoclimate. The key to gypsum as an ideal paleoclimate proxy lies in its textural variants, and in this study terrestrial gypsum samples from varied locations and textural types have been analyzed by Laser Induced Breakdown Spectroscopy (LIBS) technique. Petrographic, sub-microscopic and powder X-ray diffraction characterizations confirm the presence of gypsum (hydrated calcium sulphate; CaSO4.2H2O), bassanite (semi-hydrated calcium sulphate; CaSO4.1/2H2O) and anhydrite (anhydrous calcium sulphate; CaSO4) along with accessory phases (quartz and jarosite). The principal component analysis of LIBS spectra from texturally varied gypsums can be differentiated from one another because of the chemical variability in their elemental concentrations. The concentration of gypsum is determined from the partial least-square regressions model. Rapid characterization of gypsum samples with LIBS is expected to work well in extraterrestrial environments.

The effect of Amaranthus cruentus L. seed oil (AmO) on collagen biosynthesis and wound healing was studied in cultured human dermal fibroblasts exposed to UVA radiation. It has been found that UVA radiation inhibited collagen biosynthesis, prolidase activity, expression of β1-integrin receptor, phosphorylated ERK1/2 and TGF-β, while increased the expression of p38 kinase. The AmO at 0.05-0.15% counteracted the above effects induced by UVA radiation in fibroblasts. UVA radiation also induced the expression and nuclear translocation of pro-inflammatory NF-κB fac-tor and enhanced the COX-2 expression. AmO effectively suppressed the expression of these pro-inflammatory factors induced by UVA radiation. Expressions of β1 integrin and IGF-I re-ceptors were decreased in the fibroblasts exposed to UVA radiation, while AmO counteracted the effects. Furthermore, AmO stimulated fibroblast’s migration in a wound healing model, thus facilitating the repair process following exposure of fibroblasts to UVA radiation. This data suggest the potential of AmO to counteract UVA-induced skin damage.

Introduction the outbreak of the Israel-Gaza conflict, initiated by a major attack on the civilian population in Israel provided a tragic opportunity to study the community wide association between severe emotional stressors related to acts of war and the incidence and clinical characteristics of Takotsubo cardiomyopathy (TCM) in this scenario. Methods Eight consecutive cases of TCM diagnosed during the first 50 days of the Israel-Gaza conflict were retrospectively collected from two southern medical centers who provided care to most of the war victims throughout the period of monitoring. The medical records were thoroughly reviewed and analyzed. Results During the monitoring period, the incidence of TCM increased substantially compared to the control period. Eight patients were included in the analysis. All patients were female and 100% of patients presented within the first 3 weeks of conflict whereas after this initial phase, despite the continuing war, the incidence of TCM reverted to pre-conflict levels. Two patients (25%) were under 50 years of age. All patients had hazardous clinical characteristics including severe left ventricular (LV) dysfunction (≤35%) and prolonged QTc interval (>500 ms). Five patients (62.5%) experienced complications. Nevertheless, no in-hospital mortality was reported. Conclusions Repeated exposure to severe emotional stress, on both personal and national level, due to mass crisis such as war is associated with an increased incidence of TCM potentially with high-risk phenotype in comparison to TCM following other, less potent, psychological insults.

Familial Alzheimer’s disease (FAD) can be caused by mutations in PSEN1 that encodes presenilin-1, a component of the gamma-secretase complex that cleaves amyloid precursor protein. Alterations in calcium (Ca2+) homeostasis and glutamate signaling are implicated in the pathogenesis of FAD, however it has been difficult to assess in humans whether or not these phenotypes are the result of amyloid or tau pathology. This study aimed to assess early calcium and glutamate phenotypes of FAD by measuring the Ca2+ response of induced pluripotent stem cell (iPSC)-derived neurons bearing PSEN1 mutations to glutamate and the ionotropic glutamate receptor agonists NMDA, AMPA and kainate compared to isogenic control and healthy lines. The data shows that in early neurons, even in the absence of amyloid and tau phenotypes, FAD neurons exhibit increased Ca2+ responses to glutamate and AMPA, but not NMDA or kainate. Together this suggests that PSEN1 mutations alter Ca2+ and glutamate signaling as an early phenotype of FAD.

In contemporary construction, the prevalence of vibration serviceability issues in lightweight and slender structures has become increasingly common, owing to advancements in building materials and construction methods. While these structures often meet the criteria for ultimate limit states, they can still elicit complaints due to excessive vibrations induced by human activity. To address this challenge, the Integral Resonant Control (IRC) technique has emerged as a favored approach for actively damping vibrations in various systems. This study introduces a fresh perspective on implementing a multi-input multi-output (MIMO) IRC scheme for active vibration control (AVC) specifically tailored for pedestrian structures utilizing inertial mass actuators. Building upon a common framework and design methodology outlined in previous research, this work presents a novel application of MIMO IRC for AVC. The designed controller is rigorously tested and implemented on a laboratory floor structure to validate its efficacy.

Hiccups can significantly reduce the quality of life of patients and can occur as a drug side effect. Previous report using the Drug Adverse Event Database revealed sex-specific differences in the incidence of drug-induced hiccups. However, the pathogenesis of drug-induced hiccups remains unknown, and there is limited evidence on its treatment or prevention. This study examined molecular initiating events (MIEs), which are the starting point of adverse events, to investigate the drug-induced pathways of hiccups. We extracted drugs suspected to cause hiccups using FDA Adverse Event Reporting System, a large database on adverse drug reactions. Information on drugs suspected to be associated with hiccups were extracted from the overall population and sex-specific subgroups divided. In each data table, the predicted activity values of nuclear receptors (NRs) and stress response pathways (SPs) for each drug were calculated using the toxicity predictor, a machine-learning model. Univariate analysis extracted NRs and SPs associated with hiccups, and a multivariate analysis was performed to evaluate independent factors. Transforming growth factor-beta and antioxidant response element were considered an independent factor for hiccups in the male and female subgroups, respectively. This report first examined one of the mechanisms of drug-induced hiccups and identified MIEs associated with drug-induced hiccups.

Contrast-Induced Acute Kidney Injury (CI-AKI) remains a frequent iatrogenic condition since radiological procedures using intra-vascular iodinated contrast media (CM) are being widely administered for diagnostic and therapeutic purposes. Despite the improvement of the medical healthcare system worldwide, CI-AKI is still associated with direct short-term and indirect long-term outcomes including increased morbidity and mortality, specially, in patients under-lying pre-existing renal function impairment, cardiovascular disease or diabetes that could rap-idly progress into Chronic Kidney Disease. Although the RIFLE (Risk, Injury, Failure, Loss, End-Stage Kidney Disease), AKIN (Acute Kidney Injury Network) and KDIGO (Kidney Disease Improving Global Outcomes) clinical criteria and recommendation guidelines are based on tra-ditional “gold standard” biomarkers known as serum creatinine, glomerular filtration rate and urinary output, new reliable serum and urinary biomarkers are still needed for an effective uni-fied diagnostic strategy for AKI. Starting from previous and recent publications on the benefits and limitations of validated biomarkers responding to kidney injury, glomerular filtration and inflammation among others, this review unravels the role of new emerging biomarkers used alone or in combination, as reliable tools for early diagnosis and prognosis of CI-AKI, taking into account patients and procedures-risk factors towards a new clinical perspective.

Lichens are unique extremophilic organisms due to their phenomenal resistance to adverse environmental factors, including ultraviolet (UV) irradiation. Melanization plays a special role in the protection of lichens from UV-B stress. In present study, we analyzed the binding of melanins with the components of cell walls of mycobiont of upper cortex in the melanized lichen thalli Lobaria pulmonaria. Using scanning electron and atomic force microscopy, the morphological and nanomechanical characteristics of melanized layer of mycobiont cells were visualized. Melanization of lichen thalli led to the smoothing the surface relief and thickening mycobiont cell walls and resulted in the increase of deformation values and reduction of adhesion properties of lichen thallus. Treatment of thalli with hydrolytic enzymes, especially chitinase and lichenase, enhanced the yield of melanin from melanized thalli and release of carbohydrates, while treatment with pectinase increased the release of carbohydrates and phenols. Our results suggest that melanin by firmly binding with hyphal cell wall carbohydrates, particularly chitin and 1,4-β-glucans, can form associations, strengthen the melanized upper cortex of lichen thalli, and thereby can contribute to lichen survival under UV stress.

Controlled deposition of CoCrFeNiMo0.2 high entropy alloy (HEA) micro-particles was achieved using laser induced forward transfer (LIFT). Ultra-short laser pulses, 230 fs of 515 nm wavelength, were tightly focused into ∼ 2.4 μm focal spots on the ∼50 nm thick plasma-sputtered films of CoCrFeNiMo0.2. The HTA films were transferred onto glass substrates by magnetron sputtering in vacuum (10−8 atm) from the thermal spray coated substrates. The absorption coefficient of CoCrFeNiMo0.2 α ≈ 6 × 105 cm−1 was determined at 600 nm wavelength. The real and imaginary parts of refractive index (n + iκ) of HEA were determined from reflectance and transmittance using nano-films.

Granular superconductivity at high temperatures in graphite can emerge at certain two-dimensional (2D) stacking faults (SFs) between regions with twisted (around the c-axis) or untwisted crystalline regions with Bernal (ABA...) and/or rhombohedral (ABCABCA...) stacking order. One way to observe experimentally such 2D superconductivity is to measure the frozen magnetic flux produced by a permanent current loop that remains after removing an external magnetic field applied normal to the SFs. Magnetic force microscopy was used to localize and characterize such a permanent current path found in one natural graphite sample out of ∼50 measured graphite samples of different origins. The position of the current path drifts with time and roughly follows a logarithmic time dependence similar to the one for flux creep in type II superconductors. We demonstrate that a ≃10nm deep scratch on the sample surface at the position of the current path causes a change in its location. A further scratch was enough to irreversibly destroy the remanent state of the sample at room temperature. Our studies clarify some of the reasons for the difficulties of finding a trapped flux in remanent state at room temperature in graphite samples with SFs.

Since the discovery of the aggregation-induced emission effect in 2001, diaminodicyanoquinone derivatives (DADQs) have presented interesting fluorescence properties, allowing them to be considered fluorescent dyes capable of showing quantum yields above 90%. Besides, the diaminodiacyanoquinone core represents a versatile building block propense either to modification or integration into different systems to obtain and provide them unique photophysical features. Herein, we carried out a theoretical study on the fluorescence properties of three different diaminodicyanoquinodimethane systems. Therefore, time-dependent density functional theory (TD-DFT) was used to obtain the values associated with the dipole moments, oscillator strengths, and the conformational energies between the ground and the first excited states of each molecule. The results suggest that only two of the three studied systems possess significant luminescent properties. In a further stage, the theoretical insights were confirmed by means of experimental measurements, which not only retrieved the luminescence of the DADQs, but also suggest a preliminary and promising antibacterial activity of these systems.

Pregnancy-induced hypertension and preeclampsia are associated with significant maternal and fetal mortality. A better understanding of those diseases, delineation of molecular pathomechanism, and efficient treatment development are some of the most urgent tasks in obstetrics and gynecology. Recent findings indicate a crucial role of inflammation in the development of hypertension and preeclampsia. Although the mechanism is very complex and needs further explanation, it appears that high levels of cholesterol, urate, and glucose activates NLRP3 inflammasome, which produces IL-1β, IL-18 and gasdermin D. Production of these proinflammatory chemokines is a beginning of local and general inflammation, what results in sympathetic outflow, angiotensin II production, proteinuria, hemolysis, liver damage, immunothrombosis, and coagulopathy. NLRP3 inflammasome is a critical complex in the mediation of inflammatory response, which makes it crucial for the development of pregnancy-induced hypertension and preeclampsia, as well as its complications, such as placental abruption and HELLP syndrome. Herein presented the article delineate molecular mechanisms of those processes, indicating directions of future advance.

China historically exhibits spatial differentiation from population distribution to ecological or economic development, and the forest pest control work is an epitome of this tendency. In recent times, global warming, man-made monoculture tree plantations, increasing human population density and intensified international trade aggravate forest pest outbreaks. Although Chinese government has complied with the internationally recommended practices, few stones remain unturned due to existing differential regional imbalance of forest pest distribution and control abilities. Evidence shows that the high-income provinces in the south have taken advantage of economic and technological superiority, resulting in the adoption of more efficient pest-control measures. To the contrary, in economically underdeveloped provinces of the northwest, a paucity of financial support has led to serious threats of pest damage that almost mirrored the demarcations of the Hu Huanyong Line. In this paper, we propose introducing public-private partnership (PPP) model into forest pest control and combining the national strategies to enact regional prevention measures in order to break the current spatially differentiated trends in China.

To gain insight into riser motions and associated fatigue damage due to vortex-induced vibration (VIV), data loggers such as strain sensors and/or accelerometers are sometimes deployed on risers to monitor their motion in different current velocity conditions. Accurate reconstruction of the riser response and empirical estimation of fatigue damage rates over the entire riser length using measurements from a limited number of sensors can help in efficient utilization of the costly measurements recorded. Several different empirical procedures are described here for analysis of the VIV response of a long flexible cylinder subjected to uniform and sheared current profiles. The methods include weighted waveform analysis (WWA), proper orthogonal decomposition (POD), modal phase reconstruction (MPR), a modified WWA procedure, and a hybrid method which combines MPR and the modified WWA method. Fatigue damage rates estimated using these different empirical methods are compared and cross-validated against measurements. Detailed formulations for each method are presented and discussed with examples. Results suggest that all the empirical methods, despite different underlying assumptions in each of them, can be employed to estimate fatigue damage rates quite well from limited strain measurements.

Ionizing radiation-induced bystander effects (RIBE) encompass a number of effects with potential for a plethora of damages in adjacent non-irradiated tissue. The cascade of molecular events is initiated in response to the exposure to ionizing radiation (IR), something that may occur during diagnostic or therapeutic medical applications. In order to better investigate these complex response mechanisms, we employed a unified framework integrating statistical microarray analysis, signal normalization and translational bioinformatics functional analysis techniques. This approach was applied to several microarray datasets from Gene Expression Omnibus (GEO) related to RIBE. The analysis produced lists of differentially expressed genes, contrasting bystander and irradiated samples versus sham-irradiated controls. Furthermore, comparative molecular analysis through BioInfoMiner, which integrates advanced statistical enrichment and prioritization methodologies, revealed discrete biological processes, at the cellular level. For example, negative regulation of growth, cellular response to Zn2+- Cd2+, Wnt and NIK/NF-kappaB signalling, which refine the description of the phenotypic landscape of RIBE. Our results provide a more solid understanding of RIBE cell-specific response patterns, especially in the case of high-LET radiations like α-particles and carbon-ions.

The process of sexual reproduction in eukaryotes starts when gametes from two different sexes encounter each other. Paramecium, a unicellular eukaryote, undergoes conjugation and uses a gametic nucleus to enter the sexual reproductive process. The molecules responsible for recognizing mating partners, hypothetically called mating-type substances, are still unclear. We have identified an O3-type mating substance polypeptide and its gene sequence using protein chemistry, molecular genetics, immunofluorescence, RNA inter-ference, and microinjection. The O3-type substance is a polypeptide found in the ciliary membranes, located from the head to the ventral side of cells. The O3-type substance has a kinase-like domain in its N-terminal part located outside the cell and four EF-hand motifs that bind calcium ions in its C-terminal part located inside the cell. RNA interference and immunofluorescence revealed that this polypeptide positively correlated with the expression of mating reactivity. Microinjection of an expression vector incorporating the O3Pc-MSP gene induced additional O3 mating type in the recipient clones of different mating types or syngen. Phylogenetic analysis indicates this gene is widely present in eukaryotes and exhibits high homology among closely related species. The O3Pc-MSP gene had nine silent mutations compared to the complementary mating type of the E3 homologue gene.

Neuroinflammation is considered to be a significant component in a range of neuropathologies. Unfortunately, whilst its role is well recognized, the options for therapeutic intervention are limited. As such, there is a need to identify novel targets in order to increase treatment options. Given its role as both a neurotransmitter and an immune modulator, substance P and its NK1 receptor have been widely studied as a potential therapeutic target. There is evidence that NK1 receptor antagonists may exert beneficial effects in a range of conditions, including traumatic brain injury and stroke. Blocking the NK1 receptor has been shown to reduce blood-brain barrier dysfunction, reduce cerebral oedema, and reduce the levels of pro-inflammatory cytokines. These actions are associated with improved survival and functional outcomes. The NK1 receptor has also been shown to be involved in the inflammatory reaction to CNS infection, and hence antagonist may have some benefit in reducing infection-driven inflammation. However, the NK1 receptor may also play a role in the host immune response to infection, and so here, the potential beneficial and detrimental effects need to be carefully balanced. As such, the purpose of this review is to provide a summary of the involvement of substance P in acute inflammation, particularly in the context of traumatic brain injury and stroke.

UVA radiation inducing oxidative stress is harmful for the skin cells. The most sensitive are dermal fibroblasts. Exposure of the cells to prolonged UVA radiation induces apoptosis. Although, skin cells have a number of defense mechanisms that protect them against UV-induced oxidative stress, they are insufficient during long-lasting UV exposure. Therefore, there is a need for effective skin protection compounds with cytoprotective and antioxidant properties. One of their sources is Amaranthus cruentus L. seed oil, rich in unsaturated fatty acids, squalene, vitamin E derivatives, and phytosterols. The aim of this study was to evaluate whether Amaranthus cruentus seed oil evokes protective effect on the apoptosis stimulated by UVA radiation in human skin fibroblasts. UVA radiation at an applied dose of 10 J/cm2 caused a significant reduction in the survival of human skin fibroblasts and directed them into apoptosis pathway. Increased expression of p53, caspase 3, and caspase 9 and PARP proteins in UVA-treated fibroblasts suggests the intrinsic mechanism of apoptosis. The application of Amaranthus cruentus seed oil at 0.1% and 0.15% concentrations to UVA-treated cells decreased the expression of these proteins, which was accompanied by increased cell survival. Similarly, the UVA-dependent decrease in expression of p-Akt and mTOR proteins was restored, under the effect of studied oil. The molecular mechanism of this phenomenon is related to the stimulation of antioxidant processes through activation of Nrf2. This suggests that Amaranthus cruentus seed oil stimulate the antioxidant system in fibroblast cells and prevent the effects of UVA-induced oxidative stress and may find application in pharmacy and cosmetology as a sun- protective substance.

This study aimed to evaluate a cantilever beam-type piezoelectric energy harvester operating on train-induced vibrations for powering Wireless Sensor Networks (WSNs) used in railway track monitoring systems. The harvester's behaviors under different conditions are simulated in MATLAB using the analytical model. Natural frequency, maximum deflection, and stress were calculated with greater precision using eigenfrequency and stationary analysis using COMSOL Multiphysics. At a base excitation of 2 g and a resonant frequency of 4.38 Hz, the simulated results showed that the developed energy harvester prototype could generate up to 14 V of AC output voltage and 550 mW of output power. These findings highlight the promising potential of the proposed energy harvester for transforming train mechanical energy into electrical power. This energy harvester's viability and dependability for real-world applications in monitoring railway tracks are supported by developed analytical and simulation models.

Drugs are known to cause substantial liver injury, with hepatotoxicity ranging from asymptomatic increase of liver enzymes to hepatic failure. HIV/AIDS patients, with compromised immune systems, are especially vulnerable to opportunistic infections such as tuberculosis (TB). Patients with co-infection frequently get combined antiretroviral (ART) and antitubercular (ATD) regimens, which can cause hepatotoxicity. Hepatotoxicity has been linked to commonly administered antiretroviral drug regimens as well as first-line antitubercular agents such isoniazid, rifampin, and pyrazinamide, which are required for the treatment of both drug-sensitive and drug-resistant tuberculosis. As a result, there is an urgent need to investigate treatments based from traditional herbs known for their hepatoprotective abilities against ART and ATD-induced liver injury. Many researchers have investigated the effectiveness of medicinal plants in treating chemically caused hepatotoxicity. Medicinal plants are high in phytochemicals and secondary metabolites, both of which have a variety of medicinal benefits. Currently, there is a lack of specific therapeutic regimens to address this adverse effect, and management often relies on symptomatic treatment or therapy withdrawal. Traditional medicinal plants may have the potential to restore normal liver function, enzyme activity, and cellular structure in response to ART and ATD-induced hepatotoxicity. This review aims to examine the scientific evidence supporting the use of medicinal plants as hepatoprotective agents against liver damage induced by ART and ATDs.

Inflammation is a cause of number of disorders. Many anti-inflammatory drugs are available to cure and prevent inflammation and its related disorders. Some of the drugs are from plant and animal origin. Among animals snake venom is also utilized as treatment option of certain disorders. In the current study the venom of N. oxiana from Northern areas of Pakistan is assayed to determine its anti-inflammatory activity. The Naja oxiana is also called central Asian cobra is endemic to Central Asia. Naja oxiana belong to family Elapidae and it is highly venomous snake. The venom has many enzymatic proteins as well as nonenzymatic proteins that is neurotoxins. The venom is lethal having very high mortality rate and the death may occur due to respiratory failure in 45 minutes to 24 hrs depending upon the nature and amount of venom. As the venom is highly toxic so initially after venom milking its protein estimation was done and toxicity profile and LD50 was determined to find out its therapeutic dose at which anti-inflammatory activity was observed. The toxicity and anti-inflammatory activity was determined on mice model. Inflammation was induced by carrageenan induced peritonitis method. The inflammatory markers ROS, TNF-α and IL-β were determined by ELIZA in peritoneal fluid. The LD50 of crude venom, fraction 1 and fraction 2 was found as 34 µg/kg, 7.4 µg/kg and 416 µg/kg respectively. Anti-inflammatory activity crude venom, fraction 1 and fraction 2 was found at dose 19 µg/kg, 1.8 µg/kg and 267 µg/kg respectively. The levels of inflammatory markers reduced after therapeutic dose administration of venom and its fractions that indicates that it can be utilized as anti-inflammatory agent and so can be effective in various disorders.