Scaffolds are widely used in tissue engineering because their manufacture is based on natural and synthetic polymers, which allows them to have properties such as biocompatibility and biodegradability, creating an ideal environment for cell growth on their surface. In this context, among the polymers studied in Tissue Engineering are Chitosan (CH) and Polyvinyl Alcohol (PVA). CH is a versatile polymer obtained from de-acetylation of chitin, which is used for its high biodegradability and biocompatibility, although its mechanical properties must be improved. It has been found that one of the ways to improve the mechanical properties of CH is to mix it with other synthetic polymers such as PVA. PVA is known for its biocompatibility, biodegradability, zero toxicity and ease of preparation due to its solubility in water and excellent mechanical properties, such as tensile strength and ease in the formation of films and barriers. In this study we evaluated the capacity of scaffolds made with CH and PVA in different concentrations (2: 1, 1: 1, 1: 2, respectively) as a possible application in bone regeneration. This was made through different characterization tests such as Infrared Spectroscopy, AFM, Swelling test and Porosity test, where we obtained information about its structural and physicochemical properties. Additionally, a cellular quality control was performed on the material through the MTT assay. The Fourier transform infrared spectroscopy (FTIR) study showed that there are strong intermolecular hydrogen bonds between the chitosan and polyvinyl alcohol molecules. The Swelling and Porosity tests showed favorable results, obtaining maximum values ​​of 5519% and 72.17% respectively. MTT tests determined that the prepared materials are not cytotoxic. These findings suggest that scaffolds possess properties suitable for use in Tissue Engineering.

Recent evidence suggests the existence of shared neural resources for rhythm processing in language and music. Such overlaps could be the basis of the facilitating effect of regular musical rhythm on spoken word processing previously reported for typical children and adults, as well as adults with Parkinson’s disease and children with developmental language disorders. The present study builds upon these previous findings by examining whether musical rhythmic priming also influences visual word processing, and the extent to which such cross-modal priming effect of rhythm is related to individual differences in musical aptitude and reading skills. EEG was recorded while participants listened to a rhythmic tone prime, followed by a visual target word with a stress pattern that either matched or mismatched the rhythmic structure of the auditory prime. Participants were also administered standardized assessments of musical aptitude and reading achievement. ERPs elicited by target words with a mismatching stress pattern showed an increased fronto-central negativity. Additionally, the size of the negative effect correlated with individual differences in musical rhythm aptitude and reading comprehension skills. Results support the existence of shared neurocognitive resources for linguistic and musical rhythm processing, and have important implications for the use of rhythm-based activities for reading interventions.

This study presents a meta-analysis of studies that investigate the effectiveness of chitosan administration on lifestyle-related disease in murine models. A total of 34 published studies were used to evaluate the effect of chitosan supplementation. The effect sizes for various items after chitosan administration were evaluated using the standardized mean difference. Using Cochran’s Q test, the heterogeneity of effect sizes was assessed, after which a meta-ANOVA and –regression test was conducted to explain the heterogeneity of effect sizes using the mixed-effect model. Publication bias was performed using Egger’s linear regression test. Among the items evaluated, blood triglyceride and HDL-cholesterol showed the highest Q statistics and I2 values, respectively. Other than blood HDL-cholesterol, total cholesterol, and triglyceride in feces, most items evaluated showed a negative effect size with high significance in the fixed- and random-effect model (p<0.0001). In the meta-ANOVA and -regression test, administering chitosan and resistant starch was revealed to be most effective in lowering body weight. In addition, chitosan supplementation proved to be an effective solution for TNF-α inhibition. In conclusion, chitosan has been shown to be somewhat useful in improving symptoms of lifestyle-related disease. Although there are some limitations in the results of this meta-analysis due to the limited number of animal experiments conducted, chitosan administration nevertheless shows promise in enhancing the quality of human life.

C-reactive protein (CRP) and leukocytes are blood biomarkers involved in "Inflamm-Aging", which is a risk factor for the onset and progression of age-related diseases. Studies show that higher serum concentrations of these biomarkers are associated with functional disability, increased risk of low muscle strength, decreased muscle mass and mortality in the elderly. The objective was to estimate the predictive power and discriminating criteria of C-reactive protein and leukocyte concentrations for the risk of adverse health factors in the elderly within 30 days after hospital discharge (HD). Prospective cohort study using exploratory methods and blood biomarkers with 135 older adults admitted to medical and surgical clinics at a government hospital. The elderly were monitored at home after 30 days of HD for adverse health factors (rehospitalization, falls, amount of medication consumed, disability in basic and instrumental activities of daily living and mortality). CRP> 2.4; ≥ 0.7 and> 24.7 mg / dL and leukocytes ≥ 6.410; ≥ 8.690 and> 8.310 mm³ were discriminant for rehospitalization, falls and mortality within 30 days after HD, respectively. The cut-off points described may be used as a reference in the screening of hospitalized elderly vulnerable to adverse health events after hospital discharge.

Papillary thyroid carcinoma (PTC) has two main histologic variants: classical-PTC (CL-PTC) and follicular variant PTC (FV-PTC). Recently, due to its similar features to benign lesions, the encapsulated FV-PTC variant was reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Nonetheless, specific molecular signatures are not yet available. It is well known that telomere-related genome instability is caused by inappropriate DNA repair of dysfunctional telomeres and that mechanisms involved in the damaged telomere repair processing may led to detrimental outcomes, altering the 3D nuclear telomere and genome organization in cancer cells. This pilot study aimed to evaluate whether a specific nuclear telomere architecture might characterize NIFTP, potentially distinguishing it from other PTC histologic variants. Our findings demonstrate that 3D telomere profiles of CL-PTC and FV-PTC were different from NIFTP and that NIFTP more closely resembles follicular thyroid adenoma (FTA). NIFTP has longer telomeres than CL-PTC and FV-PTC samples and telomere length overlaps in NIFTP and FTA. There was no association between BRAF expression and telomere length in all tested samples. Our data showing that 3D nuclear telomere organization is altered differently in thyroid cancer variants, suggest that this parameter might guide clinical management of NIFTP. Although further investigations in a larger cohort of patients are necessary to corroborate our observations, telomere-related genomic instability might be of value in the diagnosis of NIFTP and allow for a more appropriate selection of the correct treatment.

The study is based on wide international research, the International Self-report Delinquency Study 3 (ISRD-3) and it analyses the relationship between parental presence, juvenile delinquency, and the consumption of psychotropic substances in adolescents. The data have been collected by a questionnaire ISRD-3 administered to 6021 students from 7th to 9th grade from 24 countries. The results confirmed the protective effect of dual-parent families on alcohol and drug use and committing illicit behaviours. Monoparental families and families without parents are associated with higher levels of alcohol, drug use, and deviant behaviors by young people.

According to the risk investigations of being involved in an accident, alcohol-impaired driving is one of the major causes of motor-vehicles accidents. Preventing highly intoxicated persons from driving would potentially save many lives. This paper proposes a lightweight in-vehicle alcohol detection that processes the data generated from 6-alcohol sensors (MQ-3 Alcohol Sensors) using an optimizable shallow neural network (O-SNN). The experimental evaluation results exhibit a high-performance detection system scoring a 99.8% of detection accuracy with a very short inferencing delay of 2.22 µ seconds. Hence, the proposed model can be efficiently deployed and used to discover in-vehicle alcohol with high accuracy and low inference overhead as a part of the driver alcohol detection system for safety (DADSS) system aiming at massive deployment of alcohol sensing systems that could potentially save thousands of lives annually.

At least 50% of factors predisposing to alcohol dependence (AD) are genetic and women affected with this disorder present with more psychiatric comorbidities, probably indicating different genetic factors involved. We aimed to run a genome-wide association study (GWAS) followed by a bioinformatic functional annotation of associated genomic regions in male and female patients with AD and eight related clinical measures. A genome-wide significant association of rs220677 with AD (p-value = 1.33×10^-8 calculated with the Yates-corrected Chi-square test under the assumption of dominant inheritance) was discovered in female patients. Associations of AD and related clinical measures with seven other single nucleotide polymorphisms listed in previous GWAS of psychiatric and addiction traits were differently replicated in male and female patients. The bioinformatic analysis showed that regulatory elements in the eight associated linkage disequilibrium blocks define the expression of 80 protein-coding genes. Nearly 68% of these and of 120 previously published coding genes associated with alcohol phenotypes directly interact in a single network. This study indicates that a number of genes behind the pathogenesis of AD are different in male and female patients, but implicated molecular mechanisms are functionally connected. The results also suggest the genetic basis of sex-specific psychiatric comorbidities of AD.

Following the coronavirus disease 2019 (COVID-19) pandemic, several studies have examined the possibility of correlating the virulence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, to the climatic conditions of the involved sites; however, inconclusive results have been generally obtained. Although either air temperature or humidity cannot be independently correlated with virus viability, a strong relationship between SARS-CoV-2 virulence and the specific enthalpy of moist air appears to exist, as confirmed by extensive data analysis. Given this framework, the present study involves a detailed investigation based on the first 20–30 days of the epidemic before public health interventions in 30 selected Italian provinces with rather different climates, here assumed as being representative of what happened in the country from North to South, of the relationship between COVID-19 distributions and the climatic conditions recorded at each site before the pandemic outbreak. Accordingly, a correlating equation between the incidence rate of the pandemic and the average specific enthalpy of atmospheric air was developed, and an enthalpy-based seasonal virulence risk scale was proposed as a tool to predict the potential danger of COVID-19 spread due to the persistence of weather conditions favorable to SARS-CoV-2 viability. For practical applications, a conclusive risk chart expressed in terms of coupled temperatures and relative humidity (RH) values was provided, showing that safer conditions occur in case of higher RH at the highest temperatures, and of lower RH at the lowest temperatures. The proposed risk scale was in agreement with the available infectivity data in the literature for a number of cities around the world.

The purpose of this study was to explore the association of cognition with hazardous drinking and alcohol related disorder in persons with bipolar disorder (BD). The study population included 1,268 persons from Finland with bipolar disorder. Alcohol use was assessed through hazardous drinking and alcohol related disorder including alcohol use disorder (AUD). Hazardous drinking was screened with the AUDIT-C (Alcohol Use Disorders Identification Test for Consumption) screening tool. Alcohol related disorder diagnoses were obtained from the national registrar data. Participants performed two computerized tasks from the Cambridge automated neuropsychological test battery (CANTAB) on tablet computer: the 5-choice serial reaction time task, or, reaction time (RT) test and the Paired Associative Learning (PAL) test. Association between RT-test and alcohol use was analyzed with log-linear regression, and eβ with 95% confidence intervals (CI) are reported. PAL first trial memory score was analyzed with linear regression, and β with 95% CI are reported. PAL total errors adjusted was analyzed with logistic regression and odds ratios (OR) with 95% CI are reported. After adjustment for age, education and housing status, hazardous drinking was associated with lower median and less variable RT in females while AUD was associated with a poorer PAL test performance in terms of the total errors adjusted scores in females. Our findings of positive associations between alcohol use and cognition in persons with bipolar disorder are unique.

Oxidative stress initiates and facilitates the disruption of the structural integrity of hepatic mitochondria, which leads to steatosis, steatohepatitis, fibrosis, and cirrhosis. It is now evident that mitochondrial dysfunction could be responsible for alcoholic liver disease (ALD). The challenge in treating ALD has been the limited availability of hepatoprotective agents and the lack of highly efficient delivery systems. Recent studies have shown that mitochondria-targeted therapies could address mitochondrial dysfunction (MD), which may greatly improve hepatoprotection and ALD treatment. This mini-review discusses the potential role of mitochondria-targeted antioxidants (MTAs) in the maintenance of hepatocellular integrity. This report also considers the mechanism of liver injury induced by alcohol and the progression of ALD from a mitochondrial oxidative damage perspective as well as the possible mechanistic actions of hepatoprotective antioxidants. Preliminary studies suggest the prospect of MTAs as anti-ALD and hepatoprotective agents.

This study explored intraindividual multidimensional profiles integrating psychosocial factors, namely, body image and satisfaction, weight-related self-stigma, positivity, and happiness, and behavioural-lifestyle factors, namely, adherence to a healthy diet, among Spanish adults with overweight or obesity. We further aimed to investigate the association of excess weight (i.e., measured body mass index, BMI) with the abovementioned multidimensional configurations. A convenience sample of adult individuals with excessive weight completed self-reports regarding the study variables, and their weight and height were measured. With a perspective centered on the individual, a cluster analysis established three distinct intraindividual psychosocial and diet-related profiles: a group of healthy individuals with excess weight; a group of individuals who were negatively affected by their excessive weight and showed the most distressed profile; and a group of dysfunctional individuals who seemed to be excessively unrealistic and optimistic regarding their excessive weight and unhealthy lifestyles. Furthermore, individuals in the affected cluster had higher obesity. The results showed that there are specific psychosocial and lifestyle profiles in the adult population with excess weight and that there are relationships among psychological, behavioural, and body-composition factors. For clinical application purposes, it is important to account for the heterogeneity within individuals who are obese and to individualize the interventions, with a focus from weight change to individual's overall well-being.

(1) Background: A global pandemic due to COVID-19 emerged in November 2019 and hit France in early March 2020. It not only resulted in a loss of lives but also in very strict confinement measures. The objective of this study was to understand what the determinants of the change in participants’ behavior and mental state were during the confinement. (2) Methods: An online survey was launched on April 23rd, 2020, and closed on May 7th, 2020. The final sample included 1454 participants from 24 to 65 years old. Descriptive and multivariate analyses were then performed. (3) Results: 28.7% reported having a more balanced diet, against 17.1% with a less balanced diet. 22.7% of respondents reported an increased alcohol consumption, as opposed to only 12.2% declaring a decrease and 11.2% of respondents increased their tobacco consumption, while 6.3% decreased it. 50.6% of the participants reported being more depressed, stressed, or irritable since the beginning of the lockdown. Confinement had a negative effect on every behavior studied in this survey, except for nutrition. We also found that negative mental state changes were strongly associated with nutrition, sleep, physical activity, and alcohol consumption changes.

Novel strategies have been developed to reduce or to avoid the intravitreal injections (IVTs) of the antiangiogenic (ranibizumab; RBZ) and the anti-inflammatory (triamcinolone acetonide; TA) agents used to treat vitreoretinal diseases. One of the strategies include liposomes. In this study, it was evaluated the safety and efficacy of topical triamcinolone-loaded liposomes formulation (TALF) as an adjuvant to intravitreal RBZ therapy in treatment-naive patients with neovascular age related macular degeneration (nAMD). Subjects were randomly assigned to the RBZ-TALF or the RBZ-pro re nata (RBZ-PRN) group. Patients from the RBZ-TALF group were instructed to apply TALF for a 12-month period after a single dose of RBZ. Patients from the RBZ-PRN group received three monthly RBZ-IVTs. Retreatment with RBZ was considered in case of nAMD reactivation. Related to safety, non-ocular abnormalities were observed during TALF therapy. Owing to the efficacy, non-significant differences are identified in visual acuity or central foveal thickness when the RBZ-PRN and RBZ-TALF groups are compared. Importantly the average number of RBZ injections was significantly lower in the RBZ-TALF group (2.5 ± 1.4 vs 6.1 ± 1.3 IVTs; p=0004). Therefore, TALF used as an adjuvant to RBZ reduce the number of RBZ-IVTs retreatment with optimal visual and anatomic results.

Monitoring coffee quality as a means of detecting and preventing economically motivated fraud is an important aspect of international commerce today. Therefore, there is a compelling need for rapid high throughput validated analytical techniques such as quantitative proton NMR spectroscopy for screening and authenticity testing. For this reason, we sought to validate an NMR spectroscopic method for routine screening of coffee for quality and authenticity. A factorial experimental design was used to investigate the influence of NMR device, extraction time and nature of coffee on the content of caffeine, 16-O-methylcafestol (OMC), kahweol, furfuryl alcohol and 5-hydroxymethylfurfural (HMF) in coffee. The method was successfully validated for specificity, selectivity, sensitivity and linearity of detector response. The proposed method produced satisfactory precision for all analytes in roasted coffee, except for kahweol in canephora (robusta) coffee. The proposed validated method may be used for routine screening of roasted coffee for quality and authenticity control, as its applicability was demonstrated during the recent OPSON VIII Europol-Interpol operation on coffee fraud control.

Aging is accompanied by frontal lobe and non-dominant hemisphere recruitment that supports executive functioning, such as inhibitory control, which is crucial to all cognitive functions. Yet, the spatio-temporal sequence of processing underlying successful inhibition and how it changes with age is understudied. Thus, we assessed N200 (conflict monitoring) and P300 (response inhibition, performance evaluation) event-related potentials (ERPs) in young and healthy older adults during comparably performed successful stop-signal inhibition. We additionally interrogated the continuous spatio-temporal dynamics of N200- and P300-related activation within each group. Young adults had left hemisphere dominant N200, while older adults had overall larger amplitudes and right hemisphere dominance. N200 activation was biphasic in both groups but differed in scalp topography. P300 also differed, with larger right amplitudes in young, but bilateral amplitudes in old, with old larger than young in the left hemisphere. P300 was characterized by an early parieto-occipital peak in both groups, followed by a parietal slow wave only in older adults. A temporally similar but topographically different final wave followed in both groups that showed anterior recruitment in older adults. These findings illuminate differential age-related spatio-temporal recruitment patterns for conflict monitoring and response inhibition that are critically important for understanding age-related compensatory activation.

Background: Different drugs damage the frontal cortices, particularly the prefrontal areas involved in both emotional and cognitive functions, with a consequence of decoding emotion deficits for people with substance abuse. The present study aims to explore the cognitive impairments in drug abusers through facial, body and disgust emotion recognition, expanding the investigation of emotions, processing, measuring accuracy and response velocity. Method: We enrolled 13 addicted to cocaine and 12 alcohol patients attending treatment services in Italy, comparing them with 33 matched controls. Facial emotion and body posture recognition tasks, a disgust rating task, and the Barrat Impulsivity Scale were included in the experimental assessment. Results: We found that emotional processes are differently influenced by cocaine and alcohol, suggesting that these substances impact diverse cerebral systems. Conclusion: The contribution made by the duration of consumption on emotional processing seems far less important than for cognitive processes. Drug abusers seem to be slower on elaboration of emotions and, in particular, of disgust emotion. Considering that the participants were not impaired in cognition, our data support the hypothesis that emotional impairments emerge independently from damage to cognitive functions.

Background: Drinking and smoking have economic consequences and are the main risk factors of mortality and morbidity. Disease-specific deaths attributable to using substances present the primary health indicator in this study. This analysis focuses on mortality in productive age, 15 to 64 years since those deaths are considered the highest economic burden. Method: In the analytical part, data from the Registry of deaths of the Czech Republic for 1994 to 2017 were used. The number of deaths attributable to smoking and drinking was calculated using attributable fractions, based on literature review. This research aimed to reveal the gender differences in deaths attributable to drinking and smoking, according to age, and the differences in deaths regarding smoking or drinking. Results: The mortality attributable to smoking and drinking differs across age groups and genders. The highest median share of tobacco-related deaths is in the age group, 60—64 years. The highest median share of alcoholic deaths is in the age group of 50—54 years. Conclusions: There are significant differences between genders in both, smoking and drinking. A prevention program should be targeted to different age groups.

Apathy is a fundamental neuropsychiatric symptom of Korsakoff’s syndrome (KS) and has also been reported in patients with alcohol use disorder with no (AUD) or less severe cognitive disorders (ALC). However, research on the nature of apathy is limited in these groups. Aim of this study was to examine the multidimensional nature of apathy in patients with KS, ALC and AUD. Moreover, we examined differences between apathy ratings by patients and their professional caregivers, and related apathy to everyday functioning and overall cognition. Twenty-four patients with KS, 24 patients with ALC and 21 patients with AUD participated in this study. Apathy was measured using the Apathy Motivation Index (AMI), which distinguishes behavioral, emotional and social apathy. Both patients and professional caregivers reported social apathy as most prominent symptom, compared to behavioral and emotional apathy. Apathy ratings did not differ across the three patient groups. Discrepancies between patient and caregiver ratings were observed in patients with KS and ALC, with more severe apathy reported by caregivers. Caregiver-reported behavioral and social, but not emotional, apathy was related to everyday functioning. These results show that apathy is present in a substantial proportion of patients with alcohol addiction with or without cognitive impairments.

This study explored intraindividual multidimensional profiles integrating psychosocial factors, namely, body image and satisfaction, weight-related self-stigma, positivity, and happiness, and behavioural-lifestyle factors, namely, adherence to a healthy diet, among Spanish adults with overweight or obesity. We further aimed to investigate the association of excess weight (i.e., measured body mass index, BMI) with the abovementioned multidimensional configurations. A convenience sample of adult individuals with excessive weight completed self-reports regarding the study variables, and their weight and height were measured. With a perspective centred on the individual, a cluster analysis established three distinct intraindividual psychosocial and diet-related profiles: a group of healthy individuals with excess weight; a group of individuals who were negatively affected by their excessive weight and showed the most distressed profile; and a group of dysfunctional individuals who seemed to be excessively unrealistic and optimistic regarding their excessive weight and unhealthy lifestyles. Furthermore, individuals in the affected cluster had higher obesity. The results showed that there are specific psychosocial and lifestyle profiles in the adult population with excess weight and that there are relationships among psychological, behavioural, and body-composition factors. For clinical application purposes, it is important to account for the heterogeneity within individuals who are obese.

Neuronal lesion or injury is a traditional approach to investigate neural circuit. Is any new neural pathway or new neurodegeneration related central nerve system injury? Spinal disc herniation can cause the spinal cord injury. However, the histological examination is still lack. It happened that a case of spinal disc herniation of a 10-year old dog was examined with NADPH diaphorase (N-d) histology. We did not find the N-d neurodegenerative aberrant in the tissue of the mid-rostral lumber segment besides the metamorphoses by the compression of the disc herniation. However, the severe neuropathological changes majorly occurred in the lumbosacral spinal cord. We found more diverse neurodegenerative alterations: the aging-related N-d body (ANB), megaloneurite and N-d homogeneous formazan globule in the lumbosacral spinal cord. We also found that a new circuit pathway (intermedial collateral pathway) showed by a megaloneurite between the lateral collateral pathway and the medial collateral pathway. The enormous notch caused by spinal disc herniation located at the mid-rostral lumber segments. The aging-related neurodegeneration occurred the specific lumbosacral segments. The homogeneous formazan globule was round or oval homogeneous N-d positivity which distributed in the gray matter and dorsal column. In the medulla oblongata, ANBs were revealed in the gracile nucleus, nucleus reticularis lateralis (ventrolateral spinal trigeminal nucleus) and middle of the spinal trigeminal nucleus.

The study aimed to assess the prevalence and correlates of hazardous, harmful or dependent alcohol use (HHDA) and drug use among persons 15 years and older in South Africa. In a national cross-sectional 2017 survey, 39,210 persons 15 years and older (Median=34 years) responded to a questionnaire on substance and health variables. Logistic regression was used to assess the determinants of HHDA and any drug use. Results indicate that (10.3%) engaged HHDA, 16.5% among males and 4.6% among females, and past 3-month drug use was 8.6%, 13.3% among males and 4.1% among females. In adjusted logistic regression analysis, among men, middle age (25-34 year olds), higher education, urban residence, drug use, and psychological distress were positively and Indian or Asian and White population groups were negatively associated with HHDA. Among women, middle age (25-34 year olds), Coloureds, residing on rural farms and urban areas, drug use and psychological distress were positively and older age (55 years and older), and Indians or Asians were negatively associated with HHDA. In adjusted logistic regression analysis, among men, having Grade 8-11 education, Coloureds, being unemployed, and HHDA were positively and middle and older age (25 years and older) and being a student or learner were negatively associated with past 3-month any drug use. Among women, Coloureds, Indians or Asians, and HHDA were positively and older age (45 years and older) was negatively associated with past 3-month and drug use. About one in ten participants engaged HHDA and any drug use, and several sociodemographic and health indicators were identified associated with HHDA and any drug use.

Spherical harmonic (SH) interpolation is a commonly used method to spatially up-sample sparse Head Related Transfer Function (HRTF) datasets to denser HRTF datasets. However, depending on the number of sparse HRTF measurements and SH order, this process can introduce distortions in high frequency representation of the HRTFs. This paper investigates whether it is possible to restore some of the distorted high frequency HRTF components using machine learning algorithms. A combination of Convolutional Auto-Encoder (CAE) and Denoising Auto-Encoder (DAE) models is proposed to restore the high frequency distortion in SH interpolated HRTFs. Results are evaluated using both Perceptual Spectral Difference (PSD) and localisation prediction models, both of which demonstrate significant improvement after the restoration process.

Indirubin-3′-monoxime (I3M) exhibits anti-proliferative activity in various cancer cells; however, its anti-cancer mechanism remains incompletely elucidated. This study revealed that I3M promotes the expression of death receptor 5 (DR5) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) in HCT116 p53+/+ cells, resulting in caspase-mediated apoptosis. However, this study demonstrated that HCT116 p53-/- cells are insensitive to I3M-mediated apoptosis, indicating that I3M-induced apoptosis depends on the p53 status of HCT116 cells. Additionally, in HCT116 p53-/- cells, I3M significantly increased Ras expression, while in HCT116 p53+/+ cells, it reduced Ras expression. Furthermore, I3M remarkably increased the production of reactive oxygen species (ROS), which were reduced in transient p53 knockdown, indicating that I3M-mediated apoptosis is promoted by p53-mediated ROS production. Our results also showed that I3M enhanced transcription factor C/EBP homologous protein (CHOP) expression, resulting in endoplasmic reticulum (ER) stress-mediated DR5 expression, which is upregulated by ROS production in HCT116 p53+/+ cells. Moreover, co-treatment with TRAIL synergistically enhanced I3M-induced DR5 expression, thereby triggering TRAIL-induced apoptosis of HCT116 p53+/+ cells, which was interfered by a DR5-specific blocking chimeric antibody. In summary, I3M potently enhances TRAIL-induced apoptosis by upregulating DR5 expression via p53-mediated ROS production in HCT116 p53+/+ cells. However, HCT116 p53-/- cells were resistant to I3M-mediated apoptosis, suggesting that I3M could be a promising anti-cancer candidate against TRAIL-resistant p53+/+ cancer cells.

Excessive alcohol consumption is one of the significant causes of morbidity and mortality worldwide. Alcohol is oxidized to toxic and carcinogenic acetaldehyde by alcohol dehydrogenase (ADH) and further oxidized to a non-toxic acetate by aldehyde dehydrogenase (ALDH). Emerging evidence shows that Lactobacillus and Bifidobacterium species encode alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) mediate alcohol and acetaldehyde metabolism, respectively. This study involves supplementation of Lactobacillus and Bifidobacterium probiotic mixture in humans and assessed their effects on alcohol and acetaldehyde metabolism. Here, twenty-seven wild types (ALDH2*1/*1) and the same number ofheterozygotes (ALDH2*2/*1) were recruited for the study. The enrolled participants were randomly divided into either the probiotic (Duolac ProAP4) or the placebo group. Each group received a probiotic or placebo capsule for 15 days with subsequent crossover. Primary outcomes were measurement of alcohol and acetaldehyde in the blood after the alcohol intake. Blood levels of alcohol and acetaldehyde in the ALDH2 heterozygote group were significantly downregulated in the probiotic-supplemented group with no changes in hangover score symptoms than the placebo group. No clinically significant changes were observed in safety parameters. These results suggest that probiotic has a potential to downregulate the alcohol and acetaldehyde concentrations, and their effects depend on the presence or absence of polymorphism on the ALDH2 gene.

Work-related thoughts in off-job time have been studied extensively in occupational health psychology and related fields. We provide a focused review of research on overcommitment – a component within the effort-reward imbalance model – and aim to connect this line of research to the most commonly studied aspects of work-related rumination. Drawing on this integrative review, we analyze survey data on ten facets of work-related rumination, namely (1) overcommitment, (2) psychological detachment, (3) affective rumination, (4) problem-solving pondering, (5) positive work reflection, (6) negative work reflection, (7) distraction, (8) cognitive irritation, (9) emotional irritation, and (10) inability to recover. First, we leverage exploratory factor analysis to self-report survey data from 357 employees to calibrate overcommitment items and to position overcommitment within the nomological net of work-related rumination constructs. Second, we leverage confirmatory factor analysis to self-report survey data from 388 employees to provide a more specific test of uniqueness vs. overlap among these constructs. Third, we apply relative weight analysis to quantify the unique criterion-related validity of each work-related rumination facet regarding (1) physical fatigue, (2) cognitive fatigue, (3) emotional fatigue, (4) burnout, (5) psychosomatic complaints, and (6) satisfaction with life. Our results suggest that several measures of work-related rumination (e.g., overcommitment and cognitive irritation) can be used interchangeably. Emotional irritation and affective rumination emerge as the strongest unique predictors of fatigue, burnout, psychosomatic complaints, and satisfaction with life. Our study assists researchers in making informed decisions on selecting scales for their research and paves the way for integrating research on effort-reward imbalance and work-related rumination.

Healthy life style is associated with decreased risk of chronic kidney disease (CKD) and mortality in the general population. However, there is no definitive evidence on the benefits of physical activity and other health-related behaviors in the early-stage CKD. This study aimed to explore the association between health-related behaviors and end-stage renal disease (ESRD) and mortality in the early stages of CKD. The National Health Insurance Service (NHIS) database from January 1st, 2009 to December 31st, 2016 was used to screen 83,470 subjects with early stage CKD. Cox proportional hazard regression analysis was used to evaluate the association between health-related behaviors and ESRD and death. Kaplan-Meier curves for mortality and ESRD were plotted according to the physical activity, smoking status and alcohol consumption pattern. Risk of death decreased significantly in subjects who engaged in sufficient physical activity (adjusted Hazard Ratio (HR) 0.73; 95% CI: 0.64-0.83; p < 0.001). Risk of ESRD and death increased significantly in the current smoker with adjusted HR of 1.44 (95% CI: 1.06-1.95; p < 0.02) and 1.61 (95% CI: 1.44-1.80; p < 0.001) respectively. Therefore, systematic interventions to encourage physical activity and smoking cessation need to be actively considered in the early stages of CKD.

Introduction: Osteoarthritis (OA) and age-related degeneration (ARD) are stimulants for the development of the fabella in the knee joint. This meta-analysis updates previous studies and reviews on the prevalence of the fabella in OA or ARD knee joints. In addition, it provides a quantitative estimation of the fabellar prevalence in knees having OA and ARD. Methodology: Twenty studies comprising of data from 11,056 knee joints were included in the analysis, consisting of 6,819 Knees of OA subjects (including those with age more than 40 years) and 4,237 knees of non-OA subjects (including less than 40years) knees, respectively. 2,434 knees had fabellae present in OA subjects (including more than 40years), and 844 fabellae were present in non-OA subjects (including less than 40years). The Odds and Risk Ratios were calculated. Sensitivity analysis and cumulative analysis were conducted to assess the robustness of the findings. Results: Prevalence of fabella was found to be higher in OA knees, where the Risk Ratio of developing fabella was 2.50 (2.07-3.01). Compared with this, the Risk Ratio for the incidence of fabella in OA with ARD knee was 1.84 (1.66-2.03). The bilateral occurrence of fabella was more common than unilateral. The risk of developing fabella in individuals aged less than forty-year was 63% less than individuals aged more than forty years. Conclusion: OA and ARD would increase the prevalence of fabella by 84%, thus acting as stimulants and risk factors for ossified fabella.

Given the high levels of overall volume of alcohol use, detrimental drinking patterns, and high levels of alcohol-attributable mortality and burden of disease, Lithuania implemented a series of alcohol control policies within a relatively short period of time (2008 to 2019). Based on their expected impact on alcohol consumption and alcohol-attributable harm, as well as their target population, the respective policies were classified using a set of objective criteria and expert opin-ion. The classification criteria included: positive vs. negative outcomes, mainly immediate versus delayed outcomes, and general population versus specific group outcomes. The judgement of the alcohol policy experts converged on the objective criteria, and, as a result, two tiers of inter-vention were identified: Tier 1 – general population interventions with an anticipated immediate impact; Tier 2 – other interventions aimed at the general population. In addition, interventions for specific populations were identified. This adaptable methodological approach to alcohol control policy classification is intended to provide guidance and support the evaluation of alcohol policies elsewhere, lay the foundation for the critical assessment of the respective policies to im-prove health and increase life expectancy, and to reduce crime and violence.

Alcohol and nicotine are widely-abused legal substances worldwide. Relapse to alcohol or tobacco seeking and consumption after abstinence is a major clinical challenge, and is often evoked by cue-induced craving. Therefore, disruption of the memory for the cue-drug association is expected to suppress relapse. Memories have been postulated to become labile shortly after their retrieval, during a “memory reconsolidation” process. Interference with the reconsolidation of drug-associated memories has been suggested as a possible strategy to reduce or even prevent cue-induced craving and relapse. Here, we surveyed the growing body of studies in animal models and in humans assessing the effectiveness of pharmacological or behavioral manipulations in reducing relapse by interfering with the reconsolidation of alcohol and nicotine/tobacco memories. Our review points to the potential of targeting the reconsolidation of these memories as a strategy to suppress relapse to alcohol drinking and tobacco smoking. However, we discuss several critical limitations and boundary conditions, which should be considered to improve the consistency and replicability in the field, and for development of an efficient reconsolidation-based relapse prevention therapy.

Poly(vinyl butyral-co-vinyl alcohol-co-vinyl acetate) named further PVBA was investigated as protective coating for copper corrosion in 0.9 % NaCl solution using electrochemical measurements such as, electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization associated with Atomic Force Microscopy (AFM). The PVBA coating on the copper surface (Cu-PVBA) was modeled in methanol containing PVBA. Its inhibitory properties against corrosion was comparatively discussed with those of the copper sample treated in methanol without polymer (Cu-Me) and of untreated sample (standard copper). A protective performance of PVBA coating of 80 % was computed from electrochemical measurements, for copper corrosion in NaCl solution. Also, AFM images designed a specific surface morphology of coated surface with PVBA, clearly highlighting a polymer film adsorbed on the copper surface, which presents certain deterioration after corrosion, but metal surface was not significantly affected compared to those of untreated samples or treated in methanol, in the absence of PVBA.

A recent report from the American Heart Association in 2018 shows that over 103 million American adults have hypertension. The angiotensin-converting enzyme (ACE) (EC 3.4.15.1) is a dipeptidyl carboxylase that, when inhibited, can reduce blood pressure through the renin-angiotensin system. ACE inhibitors are used as a first-line medication to be prescribed to treat hypertension, chronic kidney disease, heart failure among others. It has been suggested that ACE inhibitors can reduce the symptoms in mouse models. Despite the benefits of ACE inhibitors, previous studies also have suggested that alterations in the ACE gene are risk factors for Alzheimer’s disease (AD) and other neurological diseases. In mice, overexpression of ACE in the brain reduces symptoms of the AD-model systems. Thus, we find opposing effects of ACE on health. To clarify the effects, we dissect the functions of ACE as follows: (1) angiotensin-converting enzyme that hydrolyzes angiotensin I to make angiotensin II in the renin-angiotensin system; (2) amyloid-degrading enzyme that can hydrolyze beta-amyloid and reduce amyloid toxicity. The efficacy of the ACE inhibitors is well established in humans, while the knowledge specific to AD remains to be open for further research. We provide an overview of ACE and inhibitors that link a wide variety of age-related comorbidities from hypertension to Alzheimer’s disease to aging. ACE also serves as an example of the middle-life crisis theory that assumes deleterious events during the midlife, leading to age-related later events.

Emotional dysfunction, including flat affect and emotional perception deficits, is a specific symptom of schizophrenia disorder. We used a modified multimodal odd-ball paradigm with fearful facial expressions accompanied by congruent and non-congruent sounds to investigate the impairment of emotional perception and reaction to other people's emotions. We analyzed subjective assessments and ERP data for emotionally charging congruent and non-congruent stimuli in patients with schizophrenia and healthy peers. The results showed the deficit of multimodal perception of fearful stimuli in patients with schizophrenia compared to healthy controls. The amplitude of N50 was significantly higher in subjects of the control group for non-congruent stimuli than congruent and did not differ in patients with schizophrenia. The dynamics of P100 and N200 components confirmed the impaired sensory gating in patients with schizophrenia. The lower amplitude of P3a could be associated with deficits in verbal memory and attention, less emotional arousal, or incorrect interpretation of emotional valence as specific features of patients. The difficulties in identifying the incoherence of facial and audial components of emotional expression could be significant in understanding the psychopathology of schizophrenia.

Migraine and neuropathic pain (NP) are evocative of painful, disabling, chronic conditions which exhibit resembling symptoms and thus considered to share a common etiology. Calcitonin gene-related peptide (CGRP) has gained credit as a target for migraine management; nevertheless, the efficacy and the applicability of CGRP modifiers warrant search for more effective therapeutic targets for pain management. This scoping review overviews human studies of common pathogenic factors in migraine and NP to explore potential novel therapeutic targets. CGRP causes inflammation in the meninges; monoclonal antibodies and inhibitors target CGRP. Gluta-mate-induced hyperexcitability and subsequent sensitization are closely linked to an alteration of the tryptophan (Trp)-kynurenine (KYN) metabolic system; the Trp-KYN system may serve as a potential target. Microglial overaction is observed in migraine and NP; modifying the microglial activity may be a possible approach. Cytokine-induced inflammation is a leading hypothesis of the pathogenesis of the conditions; alleviating neuroinflammation may complement a pain-relieving armamentarium. Transient receptor potential (TRP) ion channels evoke the release of several substances; TRP ion channels may potentially emerge as new targets. The endocannabinoid system plays a major role in the pain trafficking pathway; modification of the system may open a new path toward discovery of new analgesics. Here we highlight the mechanism of those common pathogenic factors to explore therapeutic targets for innovative pain management in migraine and NP.

Urbanization induced land use land cover (LULC) changes intensify the urban heat island effects. It magnifies the risk of urban dwellers and sometimes causes the loss of human life, defined as heat-related health risk (HRHR). Hence, urban LULC planning plays a crucial role. Present study analyses the impact of composition and configuration of urban LULC defined as urban landscape metric (ULM) on HRHR in Delhi at the ward level. Firstly, the HRHR is measured by using satellite thermal and other digital data. Then, measured HRHR is validated by conducting a rapid field survey. Thirdly, ULM measured at ward level using Fragstat 4 software. Finally, both, HRHR and ULM linked with bi-variate Moran's I and impacts of ULM are assessed using ordinary least square (OLS) and spatial error (SE) regression. The result indicates the high risk is found as clustered in north-east, central and middle of south-west Delhi. Built-up density intensifies HRHR and abundance of vegetation reduce it; however, it is not similar for all vegetation patches. Larger vegetation patches surrounded by dense built-up might not able to reduce the risk as much as a large vegetation patch could in other regions. Findings can be helpful for heat resilient city planning.

Pancreatitis and alcoholic pancreatitis are serious health concerns, and there is an urgent need for effective treatment strategies. Alcohol is a known etiological factor for pancreatitis, including acute pancreatitis (AP) and chronic pancreatitis (CP). Excessive alcohol consumption induces many pathological stress responses; of particular note is endoplasmic reticulum (ER) stress and adaptive unfolded protein response (UPR). ER stress results from the accumulation of unfolded/misfolded protein in the ER and is implicated in the pathogenesis of alcoholic pancreatitis. Here we summarize the possible mechanisms by which ER stress contributes to alcoholic pancreatitis. We also discuss potential approaches targeting ER stress and UPR for developing novel therapeutic strategies for the disease.

Accumulating evidences demonstrate that the host genome's epigenetic modificationsare essential for living organisms to adapt extreme conditions.DNA methylation, covalent modifications of histone, andinter-association of non-coding RNAs facilitate the cellular manifestation ofepigenetic changes in the genome. Out of various factors involved in the epigenetic programming of the host, miRNA (microRNA) and LncRNA (Long non-coding RNA) are new generationnon-coding molecules that influence a variety of cellular processes like immunity, cellular differentiation, and tumor development. During tumor development, temporal changes in miRNA/LncRNA rheostat influence sterile inflammatory responses accompanied by the changes in the carcinogenic signalling in the host. At the cellular level, this is manifested by the up-regulation of Inflammasome and inflammatory pathways, which promotes cancer-related inflammation. In view of this, we discuss the potential of lncRNA and miRNA directed interventions in regulating inflammation and tumor development in the host.

One third of fatal car accidents and so much tragedies are due to alcohol abuse. These sad numbers could be mitigated if everyone had access to a breathalyzer anytime and anywhere. Having a breathalyzer built into a phone or a wearable could be the way to get around the reluctance to carry a separate device. Towards this goal, we propose an inexpensive breathalyzer that could be integrated in the screen of mobile devices. Our technology is based on the evaporation rate of the fog produced by the breath on the phone screen, which increases as a function of the breath alcohol content. The device simply uses a photodiode placed on the side of the screen to measure the signature of the scattered light intensity from the phone display that is guided through the stress layer of the Gorilla glass screen. A part of the display light is coupled to the stress layer via the evanescent field induced at the edge of the breath microdroplets. We demonstrate that the intensity signature measured at the detector can be linked to the blood alcohol content. We fabricated a prototype in a smartphone case powered by the phone’s battery, controlled by an application software installed in the smartphone and tested it in real-world environments. Limitations and future work toward a fully operational device are discussed.

TomoBreast hypothesized that hypofractionated 15 fractions/3 weeks image-guided radiation therapy (H-IGRT) can reduce lung-heart toxicity, as compared with normofractionated 25-33 fractions/5-7 weeks conventional radiation therapy (CRT). 123 women with stage I-II operated breast cancer were randomized to receive CRT (N=64) or H-IGRT (N=59). The primary endpoint used a four-items measure of the time to 10% alteration in any of patient self-reported measure, physician clinical evaluation, echocardiography or lung function tests, analyzed by intention-to-treat without exclusion. Results found comparable survivals, but H-IGRT significantly reduced the toxicity measured by lung diffusion capacity and alveolar volume as compared with CRT, G1 in 53% (31/59) versus 72% (44/61) patients, P=0.006; G2, 29% versus 48%, P=0.020. H-IGRT significantly reduced the risk of composite cardio-pulmonary alteration at 5 years, 10.2% versus 26.7%, P=0.024. In conclusion, TomoBreast is a proof-of-concept that image-guided radiation-therapy can improve the overall balance of lung-heart outcomes in breast cancer adjuvant therapy. Furthermore, the significance of the findings supports the efficacy of a small trial size design, which can be critical when clinical research resources are limited.

Biological, environmental, behavioral, and social factors can influence sleep and lead to sleep disorders or diseases. Sleep disorders are common, numerous and heterogeneous in terms of their etiology, pathogenesis, and symptomatology. Management of sleep-wake circadian disorders (SWCD) includes education to sleep hygiene, behavioral strategies, psychotherapy (cognitive behavioral therapy (CBT), particularly), instrument-based treatments (i.e. positive airway pressure therapy, hypoglossal nerve stimulation), and pharmacotherapy. Depending on the disease, therapy varies and is executed sequentially, or can be a combination of several forms of therapy. Drugs used for SWCD include traditional sleep or wake-promoting agents, chronotherapeutic agents. Recently, novel medications, which are more precisely acting on specific neurochemical systems (i.e. orexin system) important for sleep and wake, are also increasingly being used. In this review, the pharmacotherapy of common sleep disorders (insomnia, sleep-related breathing disorder, central disorders of hypersomnolence, circadian rhythm sleep wake disorders, parasomnias, and sleep-related movement disorders) embedded in the overall therapeutic concept of each disorder is presented. There is also an outlook on possible future pharmacotherapies.

Polyvinyl guanidineacetic (PVG) was prepared by the chemical grafting between poly(vinyl alcohol) (PVA) and guanidineacetic acid. The results showed that the guanidineacetic groups were successfully introduced into the polyvinyl alcohol by fourier transform infrared (FTIR) and thermogravimetry (TG). The effects of the amount of catalyst and reaction time on the PVG grafting rate were investigated. The PVG/NWF composite membrane as a heterogeneous catalyst for biodiesel production was successfully prepared by the solvent phase inversion. The effects of mass ratio of methanol/soybean oil and reaction temperature on the conversions using the composite membrane for transesterification were studied. And the reusability of the composite membrane and the kinetics of the reaction catalyzed by the composite membrane were also investigated. The conversions obtained from the model are in good agreement with the experimental data.

Building on the job demands-resources (JD-R) and the allostatic load (AL) models, in this study we investigated the role of smart working (SW) in the longitudinal association between workload/job autonomy (JA) and a possible biomarker of work-related stress (WRS) in the hair, namely the cortisol to dehydroepiandrosterone sulphate (DHEA(S)) ratio, during the COVID-19 pandemic. Overall, 124 workers completed a self-report questionnaire (i.e., psychological data) at Time 1 (T1) and collected a strand of hair (i.e., biological data) three months later (Time 2, T2). Results from moderated multiple regression analysis showed that smart working at T1 was negatively associated with hair cortisol/DHEA(S) ratio at T2. Additionally, the interaction between workload and SW was significant, with workload at T1 being positively associated with hair cortisol/DHEA(S) ratio at T2 among smart workers. Overall, this study indicates that SW can be conceived as a double-edged sword, with both positive and negative consequences on employee well-being. Furthermore, our findings suggest that hair cortisol/DHEA(S) ratio is a promising biomarker of WRS. Practical implications that organizations and practitioners can adopt to promote organizational well-being are discussed.

Binge drinking is associated with increased mortality and morbidity. Burkholderia pseudomallei, the causative agent of pneumonic melioidosis can occur in healthy humans; however, binge alcohol intoxication is a major risk factor. Previous findings indicate that a single binge alcohol episode increases Burkholderia spp. infection by reducing alveolar macrophage function. The aim of this study was to test the ability of the phytonutrient sulforaphane (SFN) to rescue the phagocytic function of alveolar macrophages when infected with Burkholderia spp. in vitro. B. thailandensis E264 was used as a useful BSL-1 model to determine the effects of SFN pre-treatment. The primary outcome was macrophage phagocytic killing, while the secondary outcome was the nuclear factor (erythroid-derived 2)-like (Nrf2) signaling response measured by western blot analysis. Results indicate that alveolar macrophages pre-treated with SFN (5 M) and challenged with 0.2% (v/v) alcohol for 3 or 8 h prior to live B. thailandensis infection improved intracellular killing of B. thailandensis ~2-fold compared to MH-S cells treated with alcohol alone. These data demonstrate that SFN may be an effective pre-treatment option to prevent alcohol mediated immune dysfunction and restore macrophage phagocytic killing of Burkholderia spp. and other similar opportunistic pathogens.

The influence of distant London dispersion forces on the docking preference of alcohols of different size between the two lone electron pairs of the carbonyl group in pinacolone is explored by infrared spectroscopy of the OH stretching fundamental in supersonic jet expansions of 1:1 solvate complexes. Experimentally, no pronounced tendency of the alcohol to switch from the methyl to the bulkier tert-butyl side with increasing size is found. In all cases, methyl docking dominates by at least a factor of two, whereas DFT-optimized structures suggest a very close balance for the larger alcohols, once corrected by CCSD(T) relative electronic energies. Together with inconsistencies when switching from a C4 to a C5 alcohol, this points at deficiencies of the investigated B3LYP and in particular TPSS functionals even after dispersion correction, which cannot be blamed on zero point energy effects. The search for density functionals which describe the harmonic frequency shift, the structural change and the energy difference between the docking isomers of larger alcohols to unsymmetric ketones in a satisfactory way is open.

The combination of statistical learning technologies with large databases of psychophysiological data has appropriately generated enthusiastic interest in future clinical applicability. It is argued here that this enthusiasm should be tempered with the understanding that significant obstacles must be overcome before the systematic introduction of psychophysiological measures into neuropsychiatric practice becomes possible. The nonspecificity of psychophysiological measures complicates their use in diagnosis. Low test-retest reliability complicates use in longitudinal assessment, and quantitative psychophysiological measures can normalize in response to placebo intervention. Ten cautionary observations are introduced and, in some instances, possible directions for remediation are suggested.

The identification of homogeneous flood regions is essential for regional flood frequency analysis. Despite the type of regionalization framework considered (e.g., region of influence or hierarchical clustering), selecting flood-related attributes to reflect flood generating mechanisms is required to discriminate flood regimes among catchments. To understand how different attributes perform across Canada for identifying homogeneous regions, this study examines five distinctive attributes (i.e., geographical proximity, flood seasonality, physiographic variables, monthly precipitation pattern, and monthly temperature pattern) for their ability to identify homogeneous regions at 186 gauging sites. We add an automatic component to enhance identification of homogeneous regions is proposed as an addition to the region of influence framework. Results are presented spatially for Canada to assess patterning of homogeneous regions. Memberships of two selected regions are investigated to provide insight into membership characteristics. Sites in eastern Canada are highly likely to identify homogeneous flood regions, while the western prairie and mountainous regions are not. Overall, it is revealed that the success of identifying homogeneous region is relevant to local hydrological complexities, to whether considered attribute reflects primary flooding mechanism, and to whether catchment sites are clustered in small geographic region. Formation of effective pooling groups affords the extension of record lengths across the Canadian domain (where gauges typically have <50 years of record), facilitating more comprehensive analysis of higher return periods floods need for climate change assessment.

Grapevine is one of the most relevant crops in the world being used for economically important products such as wine. Yet, relevant grapevine cultivars are heavily affected by diseases such as the downy mildew disease caused by Plasmopara viticola. Improvements on grapevine resistance are made mainly by breeding techniques where resistance traits are introgressed into cultivars with desired grape characteristics. However, there is still a lack of knowledge on how resistant or tolerant cultivars tackle the P. viticola pathogen. In this study, using a shotgun proteomics LC-MS/MS approach, we unravel the protein modulation of a highly tolerant grapevine cultivar, V. vinifera ‘Regent’, in the first hours post inoculation (hpi) with P. viticola. At 6 hpi, proteins related to defence and to response to stimuli are negatively modulated while at 12 hpi there is an accumulation of proteins belonging to both categories. The co-occurrence of effector-triggered susceptibility (ETS) and effector-triggered immunity (ETI) is detected at both time-points, showing that these defence processes present high plasticity. The results obtained in this study unravel the tolerant grapevine defence strategy towards P. viticola and may provide valuable insights on resistance associated candidates and mechanisms, which may play an important role in the definition of new strategies on breeding approaches.

Chromothripsis is a mutational mechanism leading to complex and relatively clustered chromosomal rearrangements resulting in diverse phenotypic outcomes depending on the involved genomic landscapes. It may occur both in the germ and the somatic cells resulting in congenital and developmental disorders and cancer, respectively. Asymptomatic individuals may be carriers of chromotriptic rearrangements and experience recurrent reproductive failures when two or more chromosomes are involved. Several mechanisms are postulated to underly chromothripsis. The most attractive hypothesis involves chromosome pulverization in micronuclei followed by incorrect reassembly of fragments through DNA repair to explain the clustered nature of the observed complex rearrangements. Moreover, exogenous or endogenous DNA damage induction and dicentric bridge formation may be involved. Chromosome instability is commonly observed in the cells of patients with DNA-repair disorders, such as ataxia telangiectasia, Nijmegen breakage syndrome and Bloom syndrome. In addition, germline variations of TP53 have been associated with chromothripsis in Sonic-Hedgehog medulloblastoma and acute myeloid leukemia. In the present review, we focus on the underlying mechanisms of chromothripsis and the involvement of defective DNA-repair genes resulting in chromosome instability and chromothripsis-like rearrangements.

Chemo-resistance is a substantial challenge in the realm of cancer treatment that requires exploring new therapeutic approaches for effective mitigation. Achieving this goal requires examination of the molecular mechanisms involved in both tumor growth and therapeutic interventions. The potential of NRF2 (Nuclear factor E2-related factor 2) in addressing resistance to chemotherapy across diverse cancer types highlights its value as a promising therapeutic approach based on cancer characteristics. Manipulating the NRF2 signaling pathway has a dual impact, offering promise for both preventing and treating cancer, as well as inhibiting carcinogenesis. The influence of the NRF2/KEAP1 pathway on the progression of tumor formation and resistance to drugs has been well-documented. The interplay between the NRF2 signaling pathway and processes such as endoplasmic reticulum (ER) stress, unfolded protein response (UPR), and autophagy plays a crucial protective role. A deeper understanding of NRF2's role in the modulating these pathways is necessary to develop novel approaches for improving chemotherapeutic efficacy. This article discusses the significance of the NRF2-KEAP1 pathway in preventing/promoting cancer and resistance mechanisms to various chemotherapeutic agents, with a focus on the complementary effects of antioxidants via NRF2-mediated signaling pathways. This study aims to provide a molecular basis for targeting NRF2 via inhibitors/activators as promising therapeutic strategies to overcome chemo-resistance.

Oligodendrocytes are myelinating cells of the central nervous system, which are generated by progenitor oligodendrocytes as a result of maturation processes. The main function of mature oligodendrocytes is to produce myelin, a lipid-rich multi-lamellar membrane that wraps tightly around neuronal axons, isolating them and facilitating nerve conduction through saltatory propagation. The myelination process requires the consumption of a lot of energy and a high metabolic turnover. Mitochondria are essential organelles which regulate many cellular functions including the energy production through oxidative phosphorylation. Any mitochondrial dysfunction impacts cellular metabolism and negatively affects the health of the organism. If the functioning of the mitochondria is unbalanced the myelination process is impaired. At the end of myelination, oligodendrocytes synthesize about 40% of the total lipids present in the brain. Since lipid synthesis occurs in the cellular endoplasmic reticulum, the alteration of this organelle can lead to partial or deficient myelination, triggering numerous neurodegenerative diseases. In this review the main dysfunctions of oligodendrocytes caused by exogenous or endogenous stimuli will be investigated. Furthermore, the oligodendrocyte reactions to excessive mitochondrial oxidative stress and an altered regulation of the functioning of the endoplasmic reticulum will be discussed.

Increased motivation towards alcohol use and suboptimal behavioural control are suggested to predispose adolescents to Alcohol Use Disorders (AUDs). Paradoxically however, most adolescent AUDs resolve over time without any formal intervention, suggesting adolescent resilience to AUDs. Importantly, studies directly comparing adolescent and adult alcohol use are largely missing. We therefore aimed to unravel the moderating role of age in the relation between alcohol use and motivational and control-related cognitive processes in 45 adolescent drinkers compared to 45 adults. The results showed that enhancement drinking motives and impulsivity related positively to alcohol use. Although enhancement drinking motives and impulsivity were higher in adolescents, the strength of the relation between these measures and alcohol use did not differ between age groups. None of the alcohol use-related motivational measures (i.e., craving, attentional bias, approach bias) and behavioral control measures (i.e., interference control, risky decision making, working-memory) were associated with alcohol use or differed between age groups. These findings support the role of impulsivity and affective sensitivity in adolescent drinking, but question the moderating role of age therein. The current study contributes towards understanding the role of age in the relation between alcohol use and cognition.

Objectives: The aim of this study was to compare the performance of the EQ-5D-Y-3L (Y-3L) and the expanded five level version, the EQ-5D-Y-5L (Y-5L). Methods: Children/adolescents with an acute or chronic health condition and from the general population completed the Y-5L and Y-3L self-report questionnaires. Performance of the Y-5L and Y-3L was determined by comparing feasibility, redistribution of dimension responses, discriminatory power, validity, and test-retest reliability. Results. Five hundred and fifty children/adolescents completed baseline measures and 173 completed repeat measures. The ceiling effect decreased by 15% from the Y-3L to Y-5L. Informativity of dimensions improved by 0.094 on the Y-5L. There was a range of 4-9% inconsistent responses moving from the Y-3L to Y-5L. Convergent validity of the Visual Analogue Scale (VAS) and Y-3L, Y-5L dimensions was similar, weak to moderate (r_s range: 0.18 – 0.38) but similar and strong on paired Y-3L and Y-5L dimensions: Kendall Tau B (range 0.69 – 0.80) and Gamma (range 0.92 – 0.98). The Y-5L and Y-3L showed moderate to substantial agreement for test-retest reliability across dimensions and VAS scores in stable chronic health conditions and fair agreement for the general population. Conclusion: The EQ-5D-Y-5L is a valid, reliable extension of the Y-3L for children/adolescents across health conditions and healthy children/adolescents. The expanded levels reduced the ceiling effect. The relative informativity of report across dimensions increased on the Y-5L compared to the Y-3L with retention of the evenness of reporting. The convergent validity and test-retest reliability of the Y-5L was comparable to the Y-3L.

Excess alcohol consumption is a top risk factor for death and disability. Fatty liver will likely develop and the risk of liver disease increases. We have previously demonstrated that an essential amino acid supplement (EAAS) improved protein synthesis and reduced intrahepatic lipid in the elderly. The purpose of this study was to further evaluate the influence of EAAS on intrahepatic lipid (IHL), body composition, and blood lipids in individuals with mild to moderate alcohol use disorder (AUD). Following consent, determination of eligibility, and medical screening, 25 participants (18 males at 38±15 years/age and 7 females at 34±18 years/age) were enrolled and randomly assigned to one of two dosages: a low dose (LD: 8 grams of EAAS twice/day (BID)) or high dose (HD: 13 grams of EAAS BID). Both groups consumed the supplement for 4 weeks. Pre- and post-EAAS administration, IHL was determined using magnetic resonance imaging/spectroscopy, body composition was analyzed using dual energy x-ray absorptiometry, and blood parameters were measured by LabCorp. T-tests were used for statistical analysis and considered significant at P<0.05. While there was no significant change in IHL in the LD group, there was a significant 23% reduction in IHL in the HD group (p=0.02). Fat mass, lean tissue mass, bone mineral content, and blood lipids were not altered. Post-EAAS phosphatidylethanol was elevated and remained unchanged in LD at 407±141 ng/ml and HD at 429±196 ng/ml, indicating chronic and excess alcohol consumption. Based on these results, we conclude that 13 grams of proprietary EAAS consumed BID lowers IHL in individuals with mild to moderate AUD.

In this study was found that these cancers were attributable to risk factors such as cigarette smoking, second-hand smoke, alcohol intake, excess body weight, diet, and six cancer-associated infections. Several databases were reviewed including PUBMED, Google scholar, and Web of Science. The facts suggest that a number of individuals present risk factors for cancer, which can be modifiable.

Dehydrolutein accumulates in substantial concentrations in the retina. The aim of this study was to compare antioxidant properties of dehydrolutein with other retinal carotenoids, lutein and zeaxanthin, and their effects on ARPE-19 cells. The time-resolved detection of characteristic singlet oxygen phosphorescence was used to compare the singlet oxygen quenching rate constants of dehydrolutein, lutein, and zeaxanthin. The effects of these carotenoids on photosensitized oxidation were tested in liposomes, where photooxidation was induced by light in the presence of photosensitizers, and monitored by oximetry. To compare the uptake of dehydrolutein, lutein, and zeaxanthin, ARPE-19 cells were incubated with carotenoids for up to 19 days, and carotenoid contents were determined by spectrophotometry in cell extracts. To investigate the effects of carotenoids on phototocytotoxicity, cells were exposed to light in the presence of rose bengal or all-trans-retinal. The results demonstrate that the rate constants for singlet oxygen quenching are 0.77x1010, 0.55x1010, and 1.23x1010 M-1s-1 for dehydrolutein, lutein and zeaxanthin, respectively. Overall, dehydrolutein is similar to lutein or zeaxanthin in protection of lipids against photosensitized oxidation. ARPE-19 cells accumulate substantial amounts of both zeaxanthin and lutein but no detectable amounts of dehydrolutein. Cells pre-incubated with carotenoids are equally susceptible to photosensitized damage as cells without carotenoids. Carotenoids provided to cells together with the extracellular photosensitizers offer partial protection against photodamage. In conclusion, the antioxidant properties of dehydrolutein are similar to lutein and zeaxanthin. The mechanism responsible for its lack of accumulation in ARPE-19 cells deserves further investigation.

Alcohol consumption is now common practice worldwide, and functional brain networks are beginning to reveal the complex interactions observed with alcohol consumption and abstinence. The autonomic nervous system (ANS) has a well-documented relationship with alcohol use, and a growing body of research is finding links between the ANS and functional brain networks. This study recruited everyday drinkers in an effort to uncover the relationship between alcohol abstinence, ANS function, and whole brain functional brain networks. Participants (n=29), 24-60 years-of-age, consumed moderate levels of alcohol regularly (males 2.4 (±0.26) drinks/day, females 2.3 (±0.96) drinks/day). ANS function, specifically cardiac vagal tone, was assessed using the Porges-Bohrer method for calculating respiratory sinus arrhythmia (PBRSA). Functional brain networks were generated from resting-state MRI scans obtained following 3-day periods of typical consumption and abstinence. A multi-task mixed-effects regression model determined the influences of HRV and drinking state on functional network connectivity. Results showed differences in the relationship between the strength of network connections and clustering coefficients across drinking states, moderated by PBRSA. Increases in connection strength between highly clustered nodes during abstinence as PBRSA increases demonstrates a greater possible range of topological configurations at high PBRSA values. This novel finding begins to shed light on the complex interactions between typical alcohol abstinence and physiological responses of the central and autonomic nervous system.

Wernicke-Korsakoff syndrome (WKS) is induced by thiamine deficiency (TD) and mainly related to alcohol consumption. Frontal cortex dysfunction has been associated to impulsivity and disinhibition in WKS patients. The pathophysiology involves oxidative stress, excitotoxicity and inflammatory responses leading to neuronal death, but the relative contributions of each factor (alcohol and TD, isolate or in interaction) to these phenomena are still poorly understood. A rat model was used by forced consumption of 20% (w/v) alcohol for 9 months (CA), TD hit (TD diet + pyrithiamine 0.25 mg/kg, i.p. daily injections the last 12 days of experimentation; TDD), and both combined treatments (CA+TDD). Motor and cognitive performance and cortical damage were examined. CA caused hyperlocomotion as a possible sensitization of ethanol-induced excitatory effects and recognition memory deficits. In addition, CA+TDD animals showed a disinhibited-like behavior, which appears to be dependent on TDD. Also, combined treatment led to more pronounced alterations in nitrosative stress, lipid peroxidation, apoptosis and cell damage markers. Correlations between injury signals and disinhibition suggest that CA+TDD disrupts behaviors dependent on the frontal cortex. Our study sheds light on the potential disease-specific mechanisms, reinforcing the need for neuroprotective therapeutic approaches along with preventive treatments for the nutritional deficiency in WKS.

Electroencephalography (EEG) enabled earbuds represent a promising frontier in evaluating brain activity beyond traditional laboratory settings. However, these devices need more comprehensive characterization before widespread health related usage. A toolbox was developed to facilitate and expand the assessment of ear-EEG devices. The first component of this toolbox is a desktop application (“EaR-P Lab”) that integrates EEG validation paradigms. This application is designed to be used with EEG amplifiers compatible with the Lab Streaming Layer (LSL) protocol. The second element of the toolbox introduces an adaptation of the phantom testing concept, to the domain of ear-EEG by using 3D ear scans of the tested individuals, allowing controlled assessment of ear-EEG devices. The EEG paradigms were validated for scalp acquisitions and applied on ear-EEG measurements, under wet ear electrode conditions. The ear-EEG phantom was successful in measuring useful metrics in EEG system characterization, highlighting performance differences within the electrodes on the tested earpieces. This knowledge was factored in to select an optimal electrode reference which resulted in increased response power on the auditory steady-state response (ASSR). Through this work, an ear-EEG evaluation toolkit is made available with the intention to enable future and systematic assessment of novel ear-EEG devices from the hardware to the neural signals.

The objective of this study was aimed to study the sensory processes of the “human-computer interaction” model when classifying visual images with an incomplete set of signs based on the analysis of early, middle, late and slow components of event-related potentials (ERPs). 26 healthy subjects (men) aged 20-22 years were investigated. ERPs in 19 monopolar sites according to the 10/20 system were recorded. Discriminant and factor analysis were applied. The component N450 is the most specialized indicator of the perception of unrecognizable (oddball) visual images. The amplitude of the ultra-late components N750 and N900 is also higher under conditions of presentation of the oddball image, regardless of the location of the registration points. The results of the study are discussed in the light of the paradigm of the P300 wave application in brain-computer interface systems, as well as with the peculiarities in brain pathology. Promising directions for the development of studies of the “Brain Computer Interface” (BCI) P300 systems are to increase the throughput of information flows. To extend the application of the P300 ERPs to multiple modalities, the underlying physiological mechanisms and responses of the brain for a particular sensory system and mental function must be carefully examined.

To investigate factors associated with the success of switching to faricimab for type 1 macular neovascularization (MNV) refractory to intravitreal aflibercept (IVA). This retrospective cohort study included patients with type 1 MNV who were switched to faricimab because they were refractory to IVA at two centers. The main outcome was an extension of the treatment interval after 6 months, and factors related to the success or failure of the extension and visual and anatomical outcomes were assessed. The analysis included 43 eyes of 43 patients. Extended dosing intervals of more than 2 weeks were identified in 14 eyes (32.6%). A short dosing interval before the switch, the absence of polypoidal lesions, and a thin central choroidal thickness before the switch were identified as factors involved in successful extension. For patients with refractory type 1 MNV, switching to faricimab is a safe and potential option to extend from existing dosing intervals.

Objectives: To explore the effect of breakthrough cancer pain (BTcP) treatment on quality of sleep and other aspects of the health-related quality of life (HRQoL) in patients with cancer pain. Methods: In an observational, multicenter, cohort study, cancer patients from palliative care units, oncology departments, and pain clinics and affected by BTcP were included. Enrolled patients were assessed at the four visits: T0 (baseline), T7, T14, and T28. Well-controlled chronic background pain during the whole study period was mandatory. BTcP was treated through transmucosal fentanyl. Three questionnaires were used to measure the HRQoL: EORTC QLQ-C15-PAL, Pittsburgh Sleep Quality Index (PSQI), and the Edmonton Symptom Assessment System (ESAS). Results: In 154 patients, the HRQoL showed a significant improvement for all physical and emotional characteristics in the EORTC QLQ-C15-PAL, except for nausea and vomiting (Linear p-value = 0.1) and dyspnoea (Linear p-value =0.05). The ESAS and PSQI questionnaires confirmed these positive results (p<0.0001 and p=0.002, respectively). Conclusions: This prospective investigation by an Italian expert group, has confirmed that careful management of BTcP induces a paramount improvement on the HRQoL. Because in cancer patients there is a high prevalence of BTcP and this severe acute pain has deleterious consequences, this information can have an important clinical significance

Purpose of the study was to explore the association of cognition with hazardous drinking, binge drinking and alcohol use disorder in schizophrenia and schizoaffective disorder. Cognitive deficits are common in schizophrenia. Alcohol might be associated with additional cognitive impairment in schizophrenia patients. The study population included 3362 schizophrenia and schizoaffective disorder patients in Finland. Hazardous drinking was screened with the AUDIT-C (Alcohol Use Disorders Identification Test for Consumption) screening tool. Binge drinking was obtained from the AUDIT-C. Alcohol use disorder (AUD) diagnoses were obtained from the national registrar data. Participants performed two computerized tasks from the Cambridge automated neuropsychological test battery (CANTAB) on tablet computer: the 5-choice serial reaction time task (5-CSRTT), or, reaction time (RT) test and the Paired Associative Learning (PAL) test. Association of alcohol use with RT test and PAL test was analyzed with log-linear regression and logistic regression, respectively. After adjustment for age, education and age at first psychotic episode, hazardous drinking in females was associated with lower median RT. Compared to never binge drinkers, male and female participants drinking 6 or more doses of alcohol monthly or less had lower median RT. In the PAL test both first trial memory score (FTMS) and total errors adjusted score (TEAS) were associated with better performance in males drinking 6 or more doses of alcohol weekly or more and in females drinking 6 or more doses monthly or less. Higher PAL TEAS was associated with AUD in females Some positive associations between alcohol and cognition were found in male and female schizophrenia and schizoaffective disorder patients with hazardous drinking and binge drinking.

Cognitive and behavioural disturbances are growing public healthcare issue for the modern society, as stressful lifestyle is becoming more and more common. Besides, several pieces of evidence state that environment is crucial in the development of several diseases as well as compromising healthy aging. Therefore, it is important to study the effects of stress on cognition and its relationship with aging. To address these queries, Chronic Mild Stress (CMS) paradigm was used in the senescence-accelerated mouse prone 8 (SAMP8) and resistant 1 (SAMR1). On one hand, we determined the changes produced in the three main epigenetic marks after 4 weeks of CMS treatment, such as a reduction in histone posttranslational modifications and DNA methylation, and up-regulation or down-regulation of several miRNA involved in different cellular processes in mice. In addition, CMS treatment induced reactive oxygen species (ROS) accumulation and loss of antioxidant defence mechanisms, as well as inflammatory signalling activation through NF-κB pathway and astrogliosis markers, like Gfap. Remarkably, CMS altered mTORC1 signalling in both strains, decreasing autophagy only in SAMR1 mice. We found a decrease in glycogen synthase kinase 3 β (GSK-3β) inactivation, hyperphosphorylation of Tau and an increase in sAPPβ protein levels in mice under CMS. Moreover, reduction in the non-amyloidogenic secretase ADAM10 protein levels was found in SAMR1 CMS group. Consequently, detrimental effects on behaviour and cognitive performance were detected in CMS treated mice, affecting mainly SAMR1 mice, promoting a turning to SAMP8 phenotype. In conclusion, CMS is a feasible intervention to understand the influence of stress on epigenetic mechanisms underlying cognition and accelerating senescence.

Alcohol use disorder (AUD) is a chronically relapsing disease characterized by loss of control in seeking and consuming alcohol (ethanol) driven by recruitment of brain stress systems. However, AUD differs among the sexes: men are more likely to develop AUD, but women progress from casual to binge drinking and heavy alcohol use more quickly. The central amygdala (CeA) is a hub of stress and anxiety, with corticotropin releasing factor (CRF)-CRF1 receptor and GABAergic signaling dysregulation occurring in alcohol dependent male rodents. However, we recently showed that GABAergic synapses in female rats are less sensitive to the acute effects of ethanol. Here, we used patch clamp electrophysiology to examine the effects of alcohol dependence on the CRF-modulation of rat CeA GABAergic transmission of both sexes. We found that GABAergic synapses of naïve female rats were unresponsive to CRF application compared males, although alcohol dependence induced a similar CRF responsivity in both sexes. In situ hybridization revealed that females had less CeA neurons containing mRNA for the CRF1 receptor (Crhr1) than males, but in dependence, the percentage of Crhr1-expressing neurons in females increased, unlike males. Overall, our data provide evidence for sexually dimorphic CeA CRF system effects on GABAergic synapses in dependence.

Abuse of amphetamine-related drugs (ARDs) causes traffic accidents, violence, and overdose. In forensic toxicology, analysis for ARDs in biological samples can help identify those driving or performing other tasks under the influence of drugs, clarify the cause of death, and identify recent drug users. In this study, we validated a pseudo-isocratic UPLC-qTOF-MS method following mixed mode cation exchange (MMSPE) extraction for analysis of ARDs in blood. The procedure requires 250 μL of blood to achieve a limit of quantification (LOQ) and detection (LOD) of 20 ng/mL for all analytes. In aged animal blood samples, extraction recoveries of 63-90% and matrix effects of 9-21% were observed. Precision and accuracy for all analytes were within 20% and 89–118%, respectively. The analytical method was developed and validated in accordance with the Scientific Working Group for Forensic Toxicology (SWGTOX) Standard. It has acceptable accuracy and precision for use in doping control and forensic toxicology.

The disruption in healthcare attention to people with alcohol dependence, along with psychological decompensation consequence of lockdown derived from COVID-19 pandemic, could have a negative impact on people who suffers from alcohol abuse disorder. Retrospective observational study of 9,966 men aged ˃16 years registered as having diagnosis of alcohol abuse disorder in the electronic medical records (EMR) of the Aragon Regional Health Service (Spain). Of those who were not infected during the study period (9,576), clinical (Glutamate-oxaloacetate -GOT-, Glutamate pyruvate -GPT-, creatinine, glomerular filtration, systolic blood pressure -SBP-, diastolic blood pressure -DBP-, total cholesterol, LDL, HDL, triglycerides, and body mass index -BMI-), pharmacological (dose per inhabitant per day -DHD- of drugs used in addictive disorders, benzodiazepines and antidepressants) and health resource use variables (primary and specialized care) were considered. Student´s T-test for matched samples was performed. After carrying out the Levene´s test, the Student´s T-test was used to analyze the changes in clinical variables between alcohol abuse disorder patients with and without COVID-19. Only creatinine and LDL show a significant but clinically irrelevant changes just after and 6 months after the end of strict lockdown. The total number of DHDs for all drugs included in the study (except for Benzodiazepines), decreased. In the same way, the use of health services by these patients also decreased. The impact of COVID-19 among this group of patients has been moderate. The reorganization of health and social services after the declaration of the state of alarm in our country, made possible the maintenance of care for this vulnerable patients.

The study aimed to assess the prevalence and correlates of heavy episodic drinking (HED) among adults in Ecuador. In the national cross-sectional 2018 Ecuador STEPS survey, 4,638 persons (median age=39 years, range 18-69 years) responded to a questionnaire, physical measures, and biomedical tests. Results indicate that 24.1% had past month HED, 36.7% among men, and 12.0% of women; 40.6% past month HED among past 12-month drinkers. In adjusted logistic regression analysis, male sex (Adjusted Odds Ratio=AOR: 3.12, 95% Confidence Interval=CI: 2.50-3.89), past smoking (AOR: 1.38, 95% CI: 1.09-1.76), and current smoking (AOR: 2.83, 95% CI: 2.15-3.83) were positively and persons aged 50-69 years (AOR: 0.50, 95% CI: 0.38-0.66) and having underweight (AOR: 0.28, 95% CI: 0.09-0.89) were negatively associated with HED. In addition, in sex-stratified analyses, among men, being African Ecuadorean or Mulato (AOR: 1.79, 95% CI: 1.10-2.91), and high physical activity (AOR: 1.41, 95% CI: 1.01-1.99) were positively associated with HED, and among women, being Montubia (AOR: 0.40, 95% CI: 0.17-0.93) was negatively and obesity (AOR: 1.61, 95% CI: 1.06, 2.44) was positively associated with HED. Almost one in four participants engaged in HED, and several sociodemographic and health indicators were identified that may facilitate public health interventions for reducing HED.

We compared the functional and morphologic effects in the loading dose between patients with treatment-naïve neovascular age-related macular degeneration treated with either intravitreal aflibercept (IVA) or intravitreal faricimab (IVF) injection in clinical settings. This retrospective study included 30 eyes from 28 patients who started IVA treatment between June and September 2022 and 30 eyes from 29 patients who started IVF treatment between October 2022 and March 2023. The mean best corrected visual acuity (BCVA) significantly improved from pre-treatment after loading dose in the IVA group (from 0.46 ± 0.46 to 0.36 ± 0.37, p=0.0047) and not in the IVF group (from 0.46 ± 0.41 to 0.44 ± 0.45, p=0.60). The mean central retinal thickness (CRT) significantly improved in both groups. The proportion of eyes with residual exudative change was greater in the IVF group than in the IVA group at 2 months after the first treatment. (p=0.026) We further analyzed the patients who obtained complete resolution of exudative changes after the loading dose. The IVA group had a significant improvement in BCVA, whereas the IVF group did not p=0.0047 and 0.20, respectively) Although IVA and IVF significantly improved the CRT, the BCVA improved significantly in IVA group and not in IVF group.

OCTA is an imaging modality used in the assessment of the retinal vasculature. It operates on the principle of coherence tomography used in standard OCT with the addition of delineating the retinal vascular. This provides a modern non-invasive retinal vascular imaging method compared to conventional dye-based imaging. High quality depth resolution of the superficial and deep capillary networks is possible on OCTA whereas this was not possible prior. OCTA may be limited by image quality degradation from factors such as motion artefact or media opacities, and therefore may not be the investigation of choice for all patient groups. There are multiple potential clinical applications for OCTA in retinal and choroidal vascular disease. Ongoing research is necessary to substantiate the more widespread use of OCTA due to its significant cost burden compared to current modalities.

Age-related macular degeneration is a progressive retinal disease that is associated with factors such as oxidative stress, decreased phagocytic activity, and inflammation. In this study, we evaluated the protective effects of SIG-1451, a non-steroidal anti-inflammatory drug developed for treating atopic dermatitis and known to inhibit toll-like receptor 4, on light-induced photoreceptor degeneration. SIG-1451 was intraperitoneally injected into rats once a day before exposure to 1000 lx light for 24 h; one day later, optical coherence tomography showed a decrease in retinal thickness, and electroretinogram (ERG) amplitude was also found to have decreased 3 d after light exposure. Moreover, SIG-1451 protected against this decrease in retinal thickness and increase in ERG am-plitude. One day after light exposure, upregulation of inflammatory response-related genes was observed, and SIG-1451 was found to inhibit this upregulation. Iba-1, a microglial marker, was suppressed in SIG-1451-injected rats. To investigate the molecular mechanism underlying these effects, we used lipopolysaccharide (LPS)-stimulated rat immortalised Müller cells. The upregu-lation of C-C motif chemokine 2　by LPS stimulation was significantly inhibited by SIG-1451 treatment, and western blot analysis revealed a decrease in phosphorylated I-κB levels. These results indicate that SIG-1451 protects photoreceptor cells by attenuating light damage progression through inhibiting inflammatory responses.

The use of New-age (Nano) Modified Emulsions (NME) for the stabilisation of marginal materials for use in the upper-pavement layers of roads have been proven in laboratories, through Accelerated Pavement Tests (APT) and in practice. In addition, material design methods have been developed based on the scientific analysis of granular material mineralogy and the chemical interaction with the binder to design a material compatible NME stabilising agent for naturally available (often marginal) materials. However, the introduction of any new disruptive technology in a traditionally well-established industry, such as the road construction industry, is usually associated with considerable resistance. This is especially relevant when the new technology enables the use of granular materials traditionally considered to be of an unacceptable quality in combination with relatively new concepts such as New-age (Nano) Modified Emulsions (NME). In practice, few road construction projects are without any problems. The introduction of new-technologies obviously makes it an easy target to blame for any non-related problem that may arise during construction. This article aims to assist in pre-empting, recognising, preventing and resolving material or non-material related construction problems through the correct identification of the cause of the problem and recommending the best, most cost-effective way to correct any deficiencies on site.

Daphne wolongensis described on the basis of a few known individuals was investigated in the wild, in Baoxing Valey, Sechuan. Its status of valid species was verified morphologically and genetically. Three newly found populations were compared to the closely related species Daphne retusa, D. tangutica, D. longilobata, D. acutiloba, D. sureil, to clones available in cultivation and selected cultivars. The high bootstrap values indicate a good level of genetic differentiation between each of the studied species. The hypothesis whether D. wolongensis is a hybridogenous species was rejected, it is a well-defined independent species. Based on morphological and genetic data, it seems likely that another species, D. limprichtii can be a mountain form of D. tangutica. Variability of populations in Wolong gives a good opportunity to select genotypes with a higher or better performance of combination of traits. From 51samples collected in Wolong it was possible to select the top ten different types as genetic resources for breeding. Daphne wolongensis, in the visited sites of Wolong area, occupies less than 1 km2. Together with isolated finds, the number of found individuals is less than 500 and the area is not larger than 10 km2, thus it falls to the IUCN category of “Critically Endangered” plants.

Disorders associated with substance abuse are a major public health crisis with few treatment options. According to World Health Organization (WHO) ethanol is the most widely used drug in the world, and it represents a risk factor for the advent of disease, disability, and eventually death. Foetal Alcoholic Spectrum Disorders (FASD) is a diagnostic term to describe the range of effects that can occur in an individual whose mother drank alcohol during pregnancy. These effects encompass both physical, mental, behavioural and further lifelong disabilities. Besides, ethanol can harm the gut microbiota. Gut microbiome is firstly acquired from the mother and it is crucial for intestinal homeostasis during hosts’ lifetime. It is responsible for producing metabolites that benefits and protects the host from harm microbial colonization. Knowledge about the interactions between human gut microbes and the developing nervous system is still scarce. Nevertheless, animal models have shown that gut bacteria and microbial metabolites are strongly associated with Central Nervous System (CNS) homeostasis. Endotoxins such as Lipopolysaccharides (LPS) are hypothesized to have a major role in neurodegeneration, however, conclusions must be taken with care due to differences in sensitivity between humans and mice. In this review we focus on the role of gut microbiota on the neurodevelopment of mice when ethanol consumption is one of the major stressors during prenatal period. We detail the range of the endotoxin hypothesis in describing endotoxins’ contribution to neurodegeneration and the influence that kynurenine pathway has on the process.

We report the first correction by Prime editing of a mutation in the RYR1 gene, paving the way to gene therapies for RYR1-related myopathies. The RYR1 gene codes for a calcium channel named Ryanodine receptor 1, which is expressed in skeletal muscle fibers. The failure of this channel causes muscle weakness in patients, which degenerates into motor disabilities. Currently, there are no effective treatments for these diseases, which are mainly caused by point mutations. Prime editing allows the modification of precise nucleotides in the DNA. Our results showed a 59% correction rate of the T4709M mutation in the RYR1 gene in human myoblasts by RNA delivery of the Prime editing components. It is to be noted that the T4709M is recessive, and thus, persons having a heterozygous mutation are healthy. These results are the first demonstration that it is possible to correct mutations in the RYR1 gene.

The COVID-19 pandemic has had a significant impact on all facets of life and has exacerbated many challenges faced by people living with tuberculosis (TB). This study aimed to assess the health-related quality of life (HRQoL) of TB patients in Guinea during the COVID-19 pandemic. A mixed-methods study was conducted using two validated psychometric tools to assess HRQoL and qualitative interviews among TB patients enrolled in treatment at three centers in Conakry, Guinea. Multinomial logistic regression was used to identify factors associated with the deterioration of HRQoL. We included 439 participants in the study, among whom 44% and 31% experienced pain and anxiety, respectively. We found that an increase in the number of household members and the distance from participants’ residence to the health centre were significantly associated with lower HRQoL. Qualitative interviews highlighted nutritional and financial concerns which were exacerbated during COVID-19 pandemic and beliefs that the Guinean Government’s assistance plan was insufficient. This study supports the implementation of specific relief plans for TB patients which includes nutritional and psychological support, especially those whose movements are limited by travel restrictions, impeding access to TB care, reducing work opportunities and exacerbating financial needs and stress.

Tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI) significantly improve the outcomes of patients with advanced clear cell renal cell carcinoma (ccRCC), but high-grade toxicities can occur, particularly during combination therapy. Herein, we report a patient with advanced metastatic ccRCC, who developed grade 4 cholestasis during combined therapy with nivolumab and cabozantinib. After the exclusion of common disorders associated with choles-tasis and a failure of corticosteroids (CS), a liver biopsy was performed that demonstrated severe ductopenia. Consequently, a diagnosis of vanishing bile duct syndrome related to TKI and ICI administration was made, resulting in CS discontinuation and ursodeoxycholic acid administra-tion. After a 7-months follow-up, liver tests had returned to normal values. Immunological studies revealed that our patient had developed robust T-cells and macrophages infiltrates in his lung metastasis, as well as in skin and liver tissues at the onset of toxicities. At the same time, peripheral blood immunophenotyping revealed significant changes in T-cell subsets suggesting their potential role in the pathophysiology of the disease.

Persistent Spinal Pain Syndrome Type 2 (PSPS-T2), (Failed Back Surgery Syndrome), dramatically impacts on patient quality of life, as evidenced by Health-Related Quality of Life (HRQoL) assessment tools. However, the importance of functioning, pain perception and psychological status in HRQoL can substantially vary between subjects. Our goal was to extract patient profiles based on HRQoL dimensions in a sample of PSPS-T2 patients and to identify factors associated with these profiles. Two classes were clearly identified using a mixture of mixed effect models from a clinical data set of 200 patients enrolled in “PREDIBACK”, a multicenter observational prospective study including PSPS-T2 patients with 1-year follow-up. We observed that HRQoL was more impacted by functional disability for first class patients (n=136) and by pain perception for second class patients (n=62). Males that perceive their work as physical were more impacted by disability than pain intensity. Lower education level, lack of adaptive coping strategies and higher pain intensity were significantly associated with HRQoL being more impacted by pain perception. The identification of such classes allows for a better understanding of HRQoL dimensions and opens the gate towards optimized health-related quality of life evaluation and personalized pain management.

This study explores the impact of the ‘pre-intervention effects’ of a community-based interventions. This refers to participatory research processes and parallel publicity in the media on changes in alcohol use and relevant mechanisms (rules and norms about alcohol, accessibility of alcohol in a formal setting) among adolescents before any intervention is implemented. In a quasi-experimental study, adolescent data were collected twice by means of self-report among adolescents living in two municipalities (control and experimental condition). Regression analysis showed pre-intervention main effects on adolescents’ perceived accessibility of alcohol in a formal setting. Moreover, among adolescents aged 15 years and older, the normative decline in strictness of rules and norms was less steep in the experimental condition compared to the control condition. Also, adolescents aged 14 years and younger in the experimental condition reported more weekly drinking compared to their peers in the control condition. No differential effects across gender were found. To conclude, applying a co-creational approach in the development of an intervention, not only contributes to more effective interventions in the end, but involvement of and discussions in the community at the start of intervention planning are contributing to changes in targeted factors. This implies that public discussions about the development of intervention strategies should be considered as an essential feature of co-creation in community-based interventions.

The COVID-19 pandemic may have increased interpersonal and intimate violence, harmful use of alcohol and other drugs (AOD), and mental health problems. The present study uses a valid path model to describe relationships between these conditions of young Mexicans during the second year of the pandemic. A sample of 7,420 young Mexicans ages 18 to 24—two-thirds of whom were women—completed the Life Events Checklist, the Alcohol, Smoking, and Substance Involvement Screening Test, the Major-Depressive-Episode Checklist, the Generalized Anxiety Scale, and the Posttraumatic Stress Disorder (PTSD) Checklist. Young Mexicans reported higher rates of victimization and perpetration of interpersonal and intimate violence and mental health symptomatology than those noted pre-pandemic and in the first year of the pandemic. Harmful use of AOD rates were like those reported by adolescents before. Findings suggested asymmetric victimization and perpetration of intimate violence by gender (with women being at a higher risk than men, p≤.05). More men than women engaged in the harmful use of AOD (except for sedatives, which more women abuse). In contrast, more women than men were at risk of all mental health conditions. The path model indicates that being a victim of intimate violence predicts harmful use of tobacco, alcohol, cocaine, and sedatives, depression, anxiety, and specific PTSD symptoms (such as re-experimentation and avoidance symptoms). Being a victim of interpersonal violence resulted in severe PTSD symptoms (including avoidance, negative alterations in cognition-mood, and hyperarousal signs). Harmful use of sedatives predicted depressive symptoms. Men´s victimizing intimate violence model contrasted with that of women, which also included being the victim of interpersonal violence and severe PTSD symptoms. The high school youth model had three paths -victimizing-intimate violence, victimizing-interpersonal abuse, and sedative use, which predicted depression. The findings of this study could serve as the basis for future studies exploring mechanisms that predict violence patterns to develop the most cost-effective preventive programs and public policies and to address mental health conditions during community emergencies.

Baeyer-Villiger monoxygenases (BVMOs) are flavin-dependant oxidative enzymes capable to catalyse the insertion of an oxygen atom between a carbonylic Csp2 and the Csp3 at the alpha position, therefore transforming linear and cyclic ketones into esters and lactones. These enzymes are dependent on nicotinamides (NAD(P)H) for the flavin reduction and subsequent reaction with molecular oxygen to furnish peroxyflavin, the ultimate responsible for the substrate oxidation. BVMOs can be included in cascade reactions, coupled to other redox enzymes such as alcohol dehydrogenases (ADHs) or ene-reductases (EREDs), so that the direct conversion of alcohols or α,β-unsaturated carbonylic compounds to the corresponding esters can be achieved. This way, it is possible to develop smart synthetic strategies with a convenient cofactor recycling, both using whole cells (native or genetically engineered) as well as isolated enzymes, via multi-steps reaction through sequential or parallel methodologies. Some examples will be commented dealing with these biotransformations, highlighting the advantages of the coupling of enzymatic steps.

This study addresses the influence of working conditions on Work-Related Quality of Life (WRQOL) among Spanish healthcare professionals. The research seeks to elucidate the mediating roles of job engagement and burnout, and the moderating effects of resilience and self-efficacy, in this relationship. Methods: The study included 374 healthcare workers from Spain, encompassing physicians, nurses, and nursing assistants. It employed a methodological approach using validated instruments to assess psychosocial risks, work-life quality, job engagement, burnout, and resilience. Data were gathered through self-reported questionnaires. Results: Key findings indicate a negative association between working conditions and WRQOL. Job engagement and burnout significantly mediated this relationship, accounting for 19% to 33% of the variance in WRQOL. Notably, lack of support emerged as a strong negative factor for work-related quality of life. Additionally, resilience moderated the relationship between lack of support and burnout. Conclusions: The study concludes that improving working conditions could increase WRQOL. Interventions aimed at enhancing engagement and addressing burnout may be effective. The moderating role of resilience suggests that strategies to enhance resilience could also be beneficial. These findings hold significant implications for policy formulation and human resources planning in healthcare, emphasizing the need for enhanced workplace support and the development of resilience among health workers.

Age-related macular degeneration is one of the most common causes of blindness, and the incidence exhibits profound racial bias, occurring most frequently in Caucasians. A primary cell type affected in the disease is the retinal pigment epithelium, but the etiology is unclear. The end 10% of the photoreceptor outer segments are shed each day, and the underlying retinal pigment epithelium engulfs, digests, and recycles molecules back to the sensory retina. In previous work, we showed that GPR143 signaling in response to L-DOPA may be effective in the prevention or delay of age-related macular degeneration. In this study, we explore a novel potential effector of GPR143 signaling, that of outer segment uptake and digestion. Using isolated outer segments, labelled with a pH-sensitive marker to fluoresce in lysosomes, we show that GPR143 signaling does not impact outer segment uptake, but does have a significant effect on subsequent degradation. Interestingly, GPR143 signaling did not affect the digestive capacity of the cells, marked by total proteolytic capacity and cathepsin D activity. Rather, our data suggest GPR143 improved endosomal trafficking efficiency of the phagocytosed outer segments to the lysosome. This result is similar to the effect we previously reported for GPR143 on exosome release from the endosomal compartment. Our data illustrate that GPR143 is active in endosomal traffic A single paragraph of about 200 words maximum. For research articles, abstracts should give a pertinent overview of the work. We strongly encourage authors to use the following style of structured abstracts, but without headings: (1) Background: Place the question addressed in a broad context and highlight the purpose of the study; (2) Methods: briefly describe the main methods or treatments applied; (3) Results: summarize the article’s main findings; (4) Conclusions: indicate the main conclusions or interpretations. The abstract should be an objective representation of the article and it must not contain results that are not presented and substantiated in the main text and should not exaggerate the main conclusions.

The human polyamines spermine and spermidine are essential for cell function, and their properties have been extensively studied. However, research results of experiments conducted without understanding the properties of polyamines have been evaluated and published by reviewers who appear to have little knowledge of the properties of polyamines. It is sad that some studies repeat what was done more than half a century ago before polyamines were characterized. First, I explain the basic properties of polyamines that researchers need to know. Then, the relationship between changes in polyamine levels in the body and age- and lifestyle-related diseases is discussed. In addition, the epigenetic mechanism of action of polyamines in relation to healthy longevity and, conversely, age- and lifestyle-related diseases and the progression of senescence are discussed. Spermine, which increases with a polyamine-rich diet, acts to suppress aberrant gene methylation and proinflammatory status associated with aging. Meanwhile, chronic inflammation associated with aging induces the enzyme activity of spermine oxidase, which breaks down spermine and produces acrolein, resulting in reduced spermine levels. Acrolein, a toxic aldehyde that increases with age- and lifestyle-related diseases, is thought to accelerate these diseases.

Frontotemporal lobar degeneration (FTLD) belongs to a heterogeneous group of highly complex neurodegenerative diseases and represents the second cause of presenile dementia in individuals under 65. Frontotemporal-TDP is a subgroup of frontotemporal dementia characterized by the aggregation of abnormal protein deposits, predominantly transactive response DNA-binding protein 43 (TDP-43), in the frontal and temporal brain regions. These deposits lead to progressive degeneration of neurons resulting in cognitive and behavioral impairments. Limbic age-related encephalopathy (LATE) pertains to age-related cognitive decline primarily affecting the limbic system which is crucial for memory, emotions, and learning. Though distinct, emerging research suggests a potential overlap in pathogenic processes, with some cases of limbic encephalopathy displaying TDP-43 pathology. Genetic factors play a pivotal role in both disorders. Mutations in various genes, such as progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72), have been identified as causative in frontotemporal-TDP. Similarly, specific genetic variants have been associated with an increased risk of developing LATE. Understanding these genetic links provides crucial insights into disease mechanisms and the potential for targeted therapies.

Unrecorded alcohol comprises all types of alcohol that is not registered in the jurisdiction where it is consumed. In some countries in Central and Eastern parts of Europe as well as the Balkan, the major amount of unrecorded alcohol consumption may derive from homeproduction of fruit spirits. Some studies found a high prevalence of lead and cadmium in such spirits. This article provides a quantitative comparative risk assessment using the margin of exposure (MOE) methodology for lead and cadmium, compared to ethanol, for unrecorded fruit spirits. For average concentration levels, the lowest MOE (0.8) was calculated for ethanol (alcohol itself). For lead, the MOE was 13 for moderate daily drinking and 0.9 for the worst case. For cadmium, the MOE was 1982 for moderate daily drinking and 113 for the worst case. The results of this study are consistent with previous comparative risk assessments that ethanol itself comprises by far the highest risk of all compounds in alcoholic beverages. Regarding the metal contaminants, the risk of cadmium appears negligible, however, lead may pose an additional health risk in heavy drinking circumstances. Strategies to avoid metal contamination in settings of artisanal homeproduction of spirits need to be developed.

Vascular calcification (VC) is associated with increased cardiovascular risks in patients with chronic kidney disease (CKD). Sodium-glucose cotransporter 2 inhibitors, like empagliflozin, can improve cardiovascular and renal outcomes. We assessed the expression of Runt-related transcription factor 2 (Runx2), interleukin (IL)-1β, IL-6, AMP-activated protein kinase (AMPK), nuclear factor erythroid-2-related factor (Nrf2), and heme oxygenase 1 (HO-1) in inorganic phosphate–induced VC in mouse VSMCs to investigate the mechanisms underlying empagliflozin’s therapeutic effects. We evaluated biochemical parameters, mean artery pressure (MAP), pulse wave velocity (PWV), transcutaneous glomerular filtration rate (GFR), and histology in an in vivo mouse model with VC induced by an oral high-phosphorus diet following a 5/6 nephrectomy in ApoE−/− mice. Compared to the control group, empagliflozin-treated mice showed significant reductions in blood glucose, MAP, PWV, and calcification, as well as increased calcium and GFR levels. Empagliflozin inhibited osteogenic trans-differentiation by decreasing inflammatory cytokine expression and increasing AMPK, Nrf2, and HO-1 levels. Empagliflozin mitigates high phosphate–induced calcification in mouse VSMCs through the Nrf2/HO-1 anti-inflammatory pathway by activating AMPK. Animal experiments suggested that empagliflozin reduces VC in CKD ApoE−/− mice on a high-phosphate diet.

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.

Abstract Background The number of immune-related endocrine dysfunctions (irEDs) has concurrently increased with the widespread use of immunotherapy in clinical practice and further expansion of the approved indications for immune checkpoint inhibitor (ICI) combinations using different modalities of anti-cancer treatment. Method A retrospective analysis was conducted on consecutive patients >18 years of age with advanced solid malignancies who had received at least one dose of anti-programmed cell death protein 1 (anti-PD-1) and/or anti-CTLA4 antibodies between January 2014 and December 2019 at a Hong Kong university hospital. Patients were reviewed for up to two months after the last administration of an ICI. The types, onset times and grades of irEDs, including hypothyroidism, hyperthyroidism, adrenal insufficiency and immune-related diabetes mellitus, were recorded. Factors associated with irEDs were identified using multivariate analysis. Result A total of 953 patients (male: 603, 64.0%; median age: 62.0 years) received ICIs during the study period. Of these, 580 patients (60.9%) used ICI-alone, 132 (13.9%) used dual-ICI, 187 (19.6%) used an ICI combined with chemotherapy (chemo+ICI), and 54 (5.70%) used immunotherapy with a targeted agent (targeted+ICI). A significantly higher proportion of patients using targeted+ICI had irEDs and hypothyroidism; in contrast, a higher proportion of patients using dual-ICI had adrenal insufficiency. There was no significant difference in the incidence of irED between the younger (<65 years) and older (>65 years) patients. Using logistic regression, only treatment type was significantly associated with irEDs. Notably, older patients had a higher risk of having immune-related diabetes mellitus. Conclusions This large, real-world cohort demonstrates that combining ICI with targeted therapy has a higher risk of overall irED and hypothyroidism. Immunotherapy is safe and well-tolerated regardless of age, but close monitoring of fasting glucose is needed in older populations.

Disease related malnutrition (DRM) is prevalent in hospitals and is associated with increased care needs, prolonged hospital stay, delayed rehabilitation and death. Nutrition care process related activities such as screening, assessment and treatment has been advocated by scientific societies and patient organizations but implementation is variable. We analyzed the cross-sectional nutritionDay database for prevalence of nutrition risk factors, care processes and outcome for medical patients. In 59126 medical patients included between 2006-2015 the prevalence of recent weight loss (45%), history of decreased eating (48%) and low actual eating (53%) was more prevalent than low BMI (8%). Each of these risk factors was associated with a large increase in 30 days hospital mortality. Nutrition care processes increases slightly with presence of risk factors but never done in more than 50% of patients. Only a third of patients not eating in hospital receive oral nutritional supplements or artificial nutrition. We suggest that political action should be taken to raise awareness and formal education on all aspects related to DRM for all stakeholders, to create and support responsibilities within hospitals, and to create adequate reimbursement schemes. Collection of routine and benchmarking data is crucial to tackle DRM.

The goal of our article was to systematize studies that investigated the impact of living conditions in large national regions on individual alcohol consumption. We sought publications on the research topic in PubMed, Google Scholar, OpenGrey, Crossref and eLibrary databases from the moment they were created until December 31, 2021. After removal of duplicates and unsuitable publications, and full-text review of remaining published sources, the final sample included 81 publications. The majority of ultimately selected papers were published after 2010, represented the United States of America, and considered samples of children and youths, either the younger population or the general adult population. High quality was characteristic for 19 studies, while satisfactory quality was exhibited by 46 publications. The most consistent associations with individual alcohol consumption were revealed for the legislative environment (especially for integral scales and indices), alcohol pricing policy, the prevalence of alcohol consumption and binge drinking in the population, and unemployment rate. Among the shortcomings of the reviewed articles, we should mention the prevailing assessment of the impact of only one type of regional characteristics, as well as the lack of studies analyzing the interaction of environmental influence at the territorial level of different scales. Protocol PROSPERO CRD42021234874.

While DNA serves as the fundamental genetic blueprint for an organism, it is not a static entity. Gene expression, the process by which genetic information is utilized to create functional products like proteins, can be modulated by a diverse range of environmental factors. Epigenetic mechanisms, encompassing DNA methylation, histone modification, and microRNAs, play a pivotal role in mediating the intricate interplay between the environment and gene expression. Intriguingly, alterations in the epigenome have the potential to be inherited across generations. Ethanol abuse poses significant health issues worldwide. Ethanol has the capability to induce changes in the epigenome, which can be inherited by offspring, thus impacting them even in the absence of direct ethanol exposure. This review article reviewed the alterations caused by ethanol on the epigenome. We thoroughly gathered all relevant papers investigating the behavioral and molecular consequences of parental ethanol exposure on their offspring. In conclusion, the comprehensive analysis of the literature supports the notion that ethanol exposure induces lasting epigenetic alterations, which can influence the behavior and health of future generations. This knowledge emphasizes the significance of addressing the potential transgenerational effects of ethanol and highlights the importance of preventive measures to minimize the adverse impact on offspring.

Orthogonal operators can successfully be used to calculate eigenvalues and eigenvector compositions in complex spectra. Orthogonality ensures least correlation between the operators and thereby more stability in the fit, even for small interactions. The resulting eigenvectors are used to transform the pure transition matrix into realistic intermediate coupling transition probabilities. Calculated transition probabilities for close lying levels illustrate the power of the complete orthogonal operator approach.

Plants respond to drought by major reprogramming of gene expression enabling the plant to survive this threatening environmental condition. One major upstream signal inducing this multifaceted process is the phytohormone abscisic acid (ABA). In this report, we investigate the drought response in barley plants (Hordeum vulgare, cv. Morex) at both epigenome and transcriptome levels. Leaves of barley plants after 10 days of drought treatment, when soil water content was decreased by about 40%, were compared to well-watered controls. Due to the drought treatment, chlorophyll content and photosystem II-efficiency were decreased by about 10% and some known drought-related genes were already induced. Global ChIPseq analyses were used to identify genes where histones 3 associated with promoter or gene body were modified with euchromatic K4 trimethylation or K9 acetylation during drought. Using stringent exclusion criteria, 129 genes loaded with H3K4me3 and 2008 genes loaded with H3K9ac in response to drought were identified, indicating that H3K9 acetylation reacts to drought more sensitive than H3K4 trimethylation. Comparison with differentially expressed genes enabled to identify those genes, which are loaded with the euchromatic marks and are induced in response to the drought treatment. The results show that a major part of these genes is involved in ABA-signaling and related pathways. Intriguingly, two members of the protein phosphatase 2C family (PP2Cs), which are involved in the central regulatory machinery of ABA signaling, were also identified by this approach.

Malaria is one of the leading causes of illnesses and deaths in Africa at large and Nigeria in particular, especially amongst pregnant women and children under the age of five years. Our research revealed that though the government has deployed so many intervention systems to contend with this death-causing vector—the mosquitoes, malaria related deaths (MRDs) have continued to increase. This is because people have not sufficiently adopted those intervention systems to protect themselves. Further enquiries into the ineffective compliance of the people to the intervention systems revealed that the interventions are passive in nature. Based on these, we set up three measurable research outcomes to enable us to determine the appropriateness of persuasive technology in solving the malaria problem. We technically avoided a one-size-fits-all design approach and adopted Participatory System Design (PSD) and User-Centered Design (UCD) approaches in our system design methodologies. Well-structured questionnaires were used to extract information from the participants. The data obtained from the research survey was used in modeling the intervention system. The research was conducted in three phases: baseline, development and deployment of an intervention system—the Malaria Prevention and Control Support System (MPCSS), and an evaluation study to determine the performance of the intervention system. The research led to the following achievements: (1) encouraged an increase in the number of people who participated in malaria prevention and control activities by lowering the rate of malaria cases from 96.9% to 68.5% and increasing ownership of mosquito nets from 54% to 85.5%; (2) demonstrated that persuasive technology could be used to increase public awareness and knowledge of a given subject as noted in our evaluation result; and (3) demonstrated that persuasive technology is a veritable active intervention to combat malaria.

High dietary phosphate intake and poor adherence to phosphate-binding-therapy elevate the risk of hyperphosphatemia in maintenance hemodialysis (HD; MHD) patients. Therefore, chronic kidney disease-related mineral and bone disorder (CKD-MBD) indicators increase; consequently, risks of CKD-MBDs and inflammation are elevated. This double-blind, randomized control trial intervention study was designed to investigate the possibility of reducing blood CKD-MBD indicators and modulating inflammatory indicators by consuming low-phosphate (LP) meals accompanied by a minimum dose of a calcium-based phosphate binder (CaCO3). MHD patients were recruited and randomly assigned to an LP meal group (LP group) or a control group. After initial data collection, blood collection, and dietary counseling, subjects were asked to consume a washout diet for 1 week. During the washout diet period, subjects consumed their usual diet but took 1 tablet of calcium carbonate (1CaCO3) as a phosphate binder with each meal. After the washout diet period, subjects in the LP group and control group respectively consumed LP meals and regular meals twice a day for 1 week. Meat in the LP meals was boiled before the regular cooking process, but meat in control meals was not. All meals were supplied by a central kitchen so that the contents of phosphate and other nutrients could be identified. In total, 40 MHD patients completed the study program. After 1 week of the dietary intervention, the blood Ca x P product and dietary phosphate had significantly decreased in the LP group compared to the control group (p&lt;0.05). The LP group had significantly lower variations in dietary phosphate intake, blood calcium, Ca x P product, and tumor necrosis factor (TNF)-α than the control group by comparing differences between after the dietary intervention and the baseline (△after intervention - baseline, p&lt;0.05). The increase in dietary phosphate intake (△3rd - 2nd dietary phosphate intake) augmented the increase in the TNF-α level by 6.24-fold (odds ratio [95% confidence interval]: 6.24 [1.12~34.92], p&lt;0.05). These results highlighted the conclusion that LP meals accompanied by a minimum dose of CaCO3 downregulated pro-inflammation by reducing CKD-MBD indicators which was triggered by decreasing dietary phosphate intake.

The persistence of diseases that affect construction workforce as a result of activities on construction sites poses a danger to the sustainable development of the industry. This resulted to a huge loss of skilled labour and economic development of the industry and the entire country. The arrival of the fourth industrial revolution (4IR) technologies urges an urgent need to assess the effect of the technology’s biological driver on the construction occupation related diseases. Therefore, this study is aimed at assessing the effect of 4IR on the construction occupation related diseases in Gauteng, South Africa. The study is quantitative in design and questionnaire survey were administered to project and Health and Safety (H&S) managers in Gauteng, South African construction sector using a proportionate simple random sampling technique. For data analysis, the Warp PLS-SEM 8.0 software algorithm was used for the analysis of the collated data. The study found that the effects of the 4IR’s biological driver variables ranges between moderate to high effects for genome sequencing (GENSE) and Neurotechnology (NEURO) respectively. The combined predictive relevance of the two (2) variables predicts 64% of the construction occupation related diseases. This implies that the adoption of the driver would help reduce the causes of construction-related diseases. Hence, implies that continuous deployment of 4IR technologies would ensure that construction occupation related diseases are easily identified and put on alert.

Device-mediated, non-invasive drug delivery across the blood-brain barrier (BBB) represents a significant advancement in treating neurological diseases. The BBB is a tightly packed layer of endothelial cells that shields the brain from harmful substances in the blood, allowing necessary nutrients to pass through. It is a highly selective barrier, which poses a challenge to delivering therapeutic agents into the brain. Several non-invasive techniques and devices have been proposed or investigated to enhance drug delivery across the BBB. This paper presents the current state of the art and case studies that address the pharmacology, technology, delivery systems, regulatory approval, ethical concerns, and future possibilities.

Forestry workers play a crucial role in implementing forest management programs, but their outdoor work exposes them to rising temperatures caused by global climate change, which poses potential health risks related to heat. This study focuses on Indonesian forestry workers and examines the relationship between their knowledge of heat-related issues, risk perception, and precautionary behavior in dealing with increasing workplace heat exposure. Developing effective precautionary behavior is essential for preventing heat-related health disorders and promoting health protection programs. To facilitate a comprehensive comparison of the three variables, interviews were conducted with two groups of outdoor workers, comprising 210 forestry workers and 215 paddy farmers. The findings indicate that increasing knowledge about heat-related issues promotes precautionary behavior, and risk perception acts as a mediator between knowledge and behavior. Additionally, the study highlights that the emotion of "dread" intensifies perceived risk and predicts positive behavior change. To enhance heat-related knowledge, exploring the potential use of a "fear" tone is important. In conclusion, comprehensive strategies need to be implemented to promote precautionary behavior among vulnerable forestry workers, particularly manual laborers.

Rotational microwave jet spectroscopy studies of the monoterpenol α-fenchol have so far failed to identify its second expected torsional conformer, despite computational predictions that it is only very slightly higher in energy than the most stable conformer. Vibrational FTIR and Raman jet spectroscopy investigations reveal unusually complex OH and OD stretching spectra compared to other alcohols. Via modelling of the torsional states, observed spectral splittings are explained by delocalization of the hydroxy hydrogen atom through quantum tunneling between the two non-equivalent but accidentally near-degenerate conformers separated by a low and narrow barrier. The energy differences between the torsional states are determined to be only 16(1) and 7(1) cm$^{−1}hc$ for the protiated and deuterated alcohol, respectively, which further shrink to 9(1) and 3(1) cm$^{−1}hc$ upon OH or OD stretch excitation. Comparisons are made with the more strongly asymmetric monoterpenols borneol and isopinocampheol as well as with the symmetric, rapidly tunneling propargyl alcohol. Assigned are also for α-fenchol the third – in contrast localized – torsional conformer and the most stable dimer, as well as for propargyl alcohol the two most stable dimers.

With a highly efficient optical absorption capability, bismuth selenide (Bi2Se3) nanomaterial can be used as an outstanding photothermal agent for anti-tumor treatment and shows promise in the field of nanotechnology-based biomedicine. However, little research has been done on the relevant mechanism underlying the photothermal killing effect of Bi2Se3 nanomaterial. Herein, the photothermal effects of Bi2Se3 nanoparticles on A549 cells were explored with emphasis put on autophagy. Firstly, we characterized the structure and physicochemical property of the synthesized Bi2Se3 and confirmed their excellent photothermal conversion efficiency (35.72%), photostability, biocompatibility and ability of photothermal killing on A549 cells. Enhanced autophagy was detected in Bi2Se3-exposed cells under an 808 nm laser. Consistently, an elevated expression ratio of LC3-II to LC3-I, a marker of autophagy occurrence, was induced in Bi2Se3-exposed cells upon NIR irradiation. Meanwhile, the expression of cleaved-PARP was increased in the irradiated cells dependently on the exposure concentrations of Bi2Se3 nanoparticles. Pharmacological inhibition of autophagy by 3-methyladenine (3-MA) further strengthened the photothermal killing effect of Bi2Se3. Meanwhile, stress-related signaling pathways including p38 and SAPK/JNK were activated coupled with the attenuated PI3K/Akt signaling. Our study figures out that autophagy and the activation of stress-related signaling pathways were involved in the photothermal killing of cancerous cells by Bi2Se3, which provides a more understanding of photothermal nanomaterials.