The aim of the study was to identify factors associated with non-adherence to tuberculosis (TB) preventive treatment among contacts with latent TB infection of new cases of pulmonary TB cases reported in Catalonia in 2019-2021. All contacts aged 18 years or older with a latent TB infection who received a TB preventive treatment were included in the study. The Chi square test and the odds ratios (OR) were used to assess the association between non-adherence to TB preventive treatment and the study variables, considering a p < 0.05 as statistically significant. Multiple logistic regression analysis was used to detect the in-dependent factors associated with TB preventive treatment non-adherence, considering a p < 0.05 as statistically significant. The percentage of non-adherence to TB preventive treatment found in this study was 23.7%. A multivariable logistic regression analysis determined that the following factors were significantly associated with TB preventive treatment non-adherence among adult contacts: “exposure at school or workplace” (aOR = 3.34), “exposure to an index case without laboratory confirmation of TB” (aOR = 2.07), “immigrant contact” (aOR = 1.81), “male gender” (aOR = 1.75) and “exposure duration <6 hours per week or sporadic exposure” (aOR = 1.60). By contrast, the factor “short-term TB preventive treatment regimen” (aOR = 0.38) was significantly associated with a lower treatment non-adherence. Adherence to TB preventive treatment should be improved among adult contacts of TB pulmonary cases with latent TB infection by recommending short-term treatment regimens and by developing health education activities, with a greater focus on contacts with factors associated with treatment non-adherence.

Tobacco and cannabis use pose major health risks and are major contributors to causes of death worldwide. Mobile phone-based cessation apps for these substances are gaining popularity, often used as a component of traditional interventions. This study aimed to analyze adherence to an intervention using a mobile phone application (App-therapy Prescind) as a function of sociodemographic variables (age, gender, educational level, and profession) as well as the primary activities supported by the app (reducing tobacco or cannabis use and increasing physical exercise). The participants were recruited through the web pages of the Occupational Risk Prevention Service and the Psychology Clinic of the University of Granada during the Covid-19 confinement period. The application’s content includes three components (self-report, motivational phrases, and goal-setting). Our findings indicate that being male, aged between 26 and 62, having a secondary or high school education, and being unemployed increase the likelihood of adherence to the Prescinde App-therapy three months after usage. Our findings highlight the importance of developing new therapeutic approaches and conducting in-depth studies on the factors associated with adherence to tobacco and cannabis cessation treatments via mobile phone applications.

Background The evolution of treatment patterns in neovascular age-related macular degeneration (nAMD) warrants investigation into the impact of patients’ adherence to anti-vascular endothelial growth factor (VEGF) treatment on visual outcomes. This retrospective, non-randomized, non-comparative study aimed to investigate real-world adherence to anti-VEGF treatment. Methods Patients (eyes) (≥ 50 years) with a diagnosis of nAMD who had a first injection of aflibercept or ranibizumab between January 2016 and December 2018 and 12 months of follow-up were included. Visual acuity (VA; logarithm of the minimum angle of resolution letters) and duration of injection intervals were recorded. Adherence was defined as < 20% of visits deviating from the schedule by ≥ 14 days. Results Overall, 133 patient eyes were included: 129 adherent, 4 non-adherent. Mean (± standard deviation) baseline VA was 57.0 (± 23.6) and 53.8 (± 35.3) letters in adherent and non-adherent patient eyes, respectively. Mean change in VA by month 12 was higher in adherent (6.3 letters) than non-adherent patient eyes (−11 letters). In non-adherent patient eyes, no improvement in VA was recorded following completion of the loading period (month 3). Compared with the previous visit, adherent visits were associated with a mean increase in VA of 0.67 letters and non-adherent visits with a decrease of 2.30 letters. Conclusions These results emphasize the importance of adherence to appropriate dosing regimens to optimize visual outcomes in patients with nAMD.

Access to health services compromises therapeutic adherence in patients with HTN, which is a risk factor for cardiovascular disease and premature death. The aim of the research is to determine the influence of access to health services on adherence to antihypertensive treatment during the COVID-19 pandemic. We included a cross-sectional analytical study. A survey was applied to 241 hypertensive patients at the Daniel Alcides Carrión Hospital, Callao-Peru. Data were analyzed using SPSS software. Absolute and relative frequencies were reported and the chi-square test was applied with a statistical significance level of p&lt;0.05. In addition, multiple logistic regression analysis was performed using the Stepwise method. An association was found between non-adherence to treatment and health expenses (ORa: 1.9 CI 95% 1.7-2.2), not receiving care due to lack of a doctor (ORa: 2.8 CI 95% 1.5-3.2), having difficulty with schedules (ORa: 3.7 CI 95% 2. 3-5.5), fear of receiving care at the hospital (ORa: 4.5 CI 95 % 2.7-6.8), trust in health personnel (ORa: 7.5 CI 95% 2.3-10.5) and considering that the physician does not have enough knowledge (ORa: 3.1 CI 95% 2.4-7.8). Therapeutic adherence was associated with physician availability for care, difficulty with schedules, fear of being seen in the hospital, trust in health personnel, and waiting time.

Proteins play a pivotal role in supporting athletes by promoting muscle hypertrophy and minimizing protein catabolism during exercise. They stimulate muscle protein synthesis, aiding in the repair of exercise-induced muscle damage and serving as an energy source, particularly for post-exercise glycogen replenishment. In individuals with phenylketonuria (PKU), for whom protein intake is limited to essential phenylalanine (Phe), supplementation with Phe-free amino acids or glycomacropeptides is necessary. Tailored for macronutrient and micronutrient content, these protein substitutes fulfill most protein requirements, but lack Phe, unlike dietary sources of protein. Protein requirements for athletes with PKU exceed general recommendations due to limited availability in supplements and potential catabolism mitigation. Various factors influence tolerated dietary Phe in PKU, including protein substitute quantity, distribution, pharmacological treatment, age, growth rate, pregnancy, catabolic states, and physical activity. While general protein requirements for PKU surpass those of the general population, adherence to supplement regimens is crucial for athletes and patients with PKU. Strategically timed protein substitutes enhance muscle protein synthesis, body composition, and sports performance within safety limits. Individualized intake is essential for optimal outcomes, as proteins have a multifaceted role in optimizing athletic performance and addressing challenges in PKU.

People must have particular personality traits and social resources, also known as health literacy, in order to access, comprehend, and use information to make decisions about their health. Patients' ability to engage in complex disease management and self-care is strongly related to their level of health literacy. It can help us stay healthy by preventing illness and effectively managing existing illnesses. People with low health literacy (LHL) may find it difficult to manage their condition and prevent illness, which may lead to increased use of healthcare services. Furthermore, LHL is associated with increased hospitalizations, increased use of emergency care, decreased use of preventative services, and a worsened ability to understand labels and health messages, a worsened state of health, higher mortality, and more expensive medical care.

Ketogenic dietary therapies (KDTs) are an effective and safe non-pharmacological treatment for drug-resistant epilepsy, but adherence can be challenging for both patients and caregivers. In Europe, there are no adequate tools to measure it other than monitoring ketosis. This study aimed to adapt and validate the Brazilian adherence questionnaire, Keto-check, into the Italian version: iKetoCheck. Using the Delphi technique, 12 judges validated the contents through agreement rate and the Content Validity Index (CVI). The iKetocheck was self-completed electronically by drug-resistant epilepsy or GLUT1 deficiency patients within an interval of 15 days to measure its reproducibility. Test-retest reliability was evaluated using Pearson correlation and relative significance test. Exploratory and confirmatory factorial analyses were made using Factor software. The final tool, iKetoCheck, consists of 10 questions with 5-point Likert scale answers. It evaluates various aspects such as informing caregivers about the diet, organization of meals, measurement of ketosis, weighing food consumed, diet negligence, use of carbohydrate-free medications, attending follow-up visits, reading food labels, consulting an expert for dietary concerns, and cooking at home. The factorial analysis resulted in three factors: "attention," "organization," and "precision," with satisfactory results for indices in exploratory and confirmatory analyses. Although higher mean values of ketonemia measurement were observed in patients with a higher adherence score, these values were not statistically significant (p=0.284). In conclusion, iKetoCheck is a valid tool for evaluating KDTs' adherence in Italian drug-resistant epilepsy or GLUT1 deficiency patients. It can provide valuable information to improve patient management and optimize the effectiveness of KDTs.

This study analysed trends of first-time patients visiting the paediatric psychiatry clinic in a university hospital. The medical records from 2009 to 2016 of first-time patients visiting the Kyung Hee university hospital were reviewed, focusing on children in grades 1–12. We analysed the prevalence rate of psychiatric disorders per 100,000 general populations by gender and grade, and the characteristics of patients who sought outpatient care more than three times. The study included 1,467 participants, of which 931 were males (63.5%). The number of male patients per 100,000 populations significantly decreased from 4.14 in 2009 to 2.03 in 2016. While hyperkinetic disorders had the highest prevalence in males, neurotic disorders were most frequent in females. Prevalence of disruptive behaviour disorders in males and mental retardations in females decreased significantly during the study period. The factors affecting continuity were being female, studying in grades 7–12, and diagnosis of depressive, hyperkinetic, and tic disorders. Physicians should consider the new paediatric patients’ gender, grade, and expected diagnosis from their first visit to improve treatment compliance.

Objective: In India, yearly, estimated one million TB cases are missing from notification, mostly from private sector. The large number of patients in private sector has raised concerns for suboptimal quality of care. This study was conducted to find out the treatment adherence status among the private TB patients and factors associated with poor adherence.Data Source: Secondary project data, obtained through adherence monitoring house visit by NGO workers. Data collected by reviewing different records available with the patients & data was entered into the CommCare HQ, an open-source mobile platform designed for data collection.Methods: Descriptive observational study.Results: Default rate among private patients was 5%. Commonest reasons stated for being a defaulter were ‘Medicine is not good’ (30%), ‘Travel’ (28.6%), ‘Cost of treatment’ (21.8%) and ‘Side effects’ (11.6%). Despite best of efforts only 36.9% defaulter could be retrieved. Higher default rate was associated with 15-59 years age, males, earning member of the family, addiction, DR-TB, continuation phase of treatment, previous history of TB, presence of symptoms and inability to walk.Conclusion: Privately treated TB patients are vulnerable to non-adherence. Once defaulted, it is difficult to retrieve them. Economically productive age group is at higher risk of being defaulter. Strict adherence monitoring for private TB patients and extensive advocacy communication & social mobilization program in the community, workplaces and institutions is a need of hour.

Denosumab is a human monoclonal antibody that neutralizes RANKL, a cytokine able to interact with the RANK receptor on preosteoclasts and osteoclasts, decreasing their recruitment and differentiation, leading to a decreased bone resorption. The aim of this observational real-life study was to analyze adherence to denosumab therapy, its effectiveness in increasing bone mineral density (BMD) and in modulating biochemical skeletal markers upon previous treatments with bisphosphonates in a group of post-menopausal women affected by osteoporosis. Women were recruited in the specialized center from March 2012 to September 2019. Biochemical markers were recorded at baseline and every six months prior to subsequent drug injection. Dual X-ray Absorptiometry was requested at baseline and after 18/24 months. Comparing BMD at baseline and after denosumab therapy in naive patients and in those previously treated with bisphosphonates, a positive therapeutic effect was observed in both groups. The results of our real-life study demonstrate, as expected, that BMD values significantly increased upon denosumab treatment. Interestingly, denosumab showed an increased effectiveness in patients previously treated with bisphosphonates. Moreover, biochemical markers data indicate that osteoporotic patients, without other concomitant unstable health conditions, could be evaluated once a year, decreasing the number of specialistic center access.

Aggregatibacter actinomycetemcomitans is a Gram-negative bacterium that is part of the oral microbiota. The aggregative nature of this pathogen or pathobiont is crucial to its involvement in human disease. It has been cultured from non-oral infections for more than a century, while the portrayal as an aetiological agent in periodontitis has emerged more recently. Although A. actinomycetemcomitans encodes several putative toxins, the complex interplay with other partners of the oral microbiota and the suppression of the initial host response may be central for inflammation and infection in the oral cavity. The aim of this review is to provide a comprehensive update on the clinical significance, classification, and characterisation of A. actinomycetemcomitans, which has exclusive or predominant host specificity for humans.

Objectives We tested the hypothesis that poor adherence is associated with a greater risk of alcohol-caused mortality and morbidities within the first year of discontinuing this medication. Materials and Methods Retrospective cohort study of 3319 individuals who received Acamprosate® in the East of Scotland in a 10-year period using a health informatics approach with record linkage of dispensing data, hospital utilization (SMR) and General Register Office of Scotland (GROS) data. Primary outcome was adherence between one to six months of initiating Acamprosate® medication. Secondary outcome was all cause morbidities and mortality. Results Of the total 3319 individuals identified, good adherence index of >80% was found in 59% of those prescribed Acamprosate® after three months and 6% after six months. There were significant linear trends of poorer adherence with increased risk of alcohol-caused mortality (HR1.2), medical morbidities especially neoplasm (HR 4.1|) and poisoning (HR 1.4) and psychiatric morbidities especially stress (HR 35.1), psychotic (HR 5.6) and neurotic disorders and directly alcohol induced conditions (7.4 HR) after adjustment for other factors within a one-year period of initiation of Acamprosate® treatment. Discussion and Conclusions Further exploratory studies using this digitalized approach should be encouraged in order to capture role of compliance to Acamprosate® and other types of medication that are known to reduce relapse into alcohol dependence and its direct relationship to mortality and morbidities in this population.

The study's objective was to assess the impact of Mediterranean diet/lifestyle interventions for weight loss on Positive airway pressure (PAP) adherence, Body mass index (ΒΜΙ), sleepiness, and blood pressure measurements (BP) in patients with obstructive sleep apnea (OSA). We designed a randomized, controlled trial, including overweight and obese patients with moderate-to-severe OSA, randomized to standard care (SCG, n=37) and Mediterranean diet group (MDG, n=37). SCG received healthy lifestyle advice, while MDG underwent a 6-month behavioral intervention aiming to enhance weight loss and adherence to Mediterranean diet. PAP adherence, BMI, Epworth Sleepiness Scale (ESS) and BP measurements were evaluated pre- and post-intervention. Post-intervention PAP use was higher in MDG compared to SCG (6.1 vs 5.4, p=0.02). Diet/lifestyle intervention was one of the most significant predictive factors for PAP adherence (OR = 5.458, 95% CI = 1.144-26.036, p=0.03). The SCG demonstrated a rise in BMI, while the MDG displayed a decline (0.41 vs -0.75, p=0.02). The MDG also demonstrated a substantial reduction in adjusted SBP (-5.5 vs 2.8, p=0.014) and DBP (-4.0 vs 2.5, p=0.01). Ultimately, incorporating a dietary/lifestyle intervention with standard care yields superior PAP adherence, BMI, and BP measurements in contrast to standard care alone, underscoring the potential benefits of allocating increased time and support within the MDG group. Trial registry: ClinicalTrials.gov; No.: NCT05881824; URL: www.clinicaltrials.gov.

This study aims to assess the acceptability, adherence, and retention of a feasibility trial on milk fortification with calcium and vitamin D (Ca+VitD) and periodontal therapy (PT) among low income Brazilian pregnant women with periodontitis (IMPROVE trial). This 2x2 factorial feasibility trial used a mixed-methods evaluation. 69 pregnant women were randomly allocated to four groups: 1.fortified sachet with Ca+VitD and milk plus early PT (throughout gestation); 2.placebo and milk plus early PT; 3.fortified sachet with Ca+VitD and milk plus late PT after childbirth; 4.placebo and milk plus late PT. Data were collected via questionnaires, field notes, participant flow logs, treatment diary, and focal group discussions. Quantitative and qualitative data were analysed using appropriate descriptive statistics and content analysis, respectively. Eligibility rate (12%) was below the target of 15%, but participation (76.1%) and recruitment rate (2 women/week) exceeded the targets. Retention rate (78.6%) was slightly below the target (80%). Adherence to the PT was significantly higher in the early treatment groups (98.8%) compared to the late treatment groups (29%). All women accepted the random allocation and baseline groups were balanced. There was no report of adverse events. This multi-component intervention is acceptable, well-tolerated, and feasible among low-risk pregnant women in Brazil.

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Despite extensive research efforts, the majority of trialed monotherapies to date have failed to demonstrate significant benefit. It has been suggested that this is due to the complex pathophysiology of TBI, which may possibly be addressed by a combination of therapeutic interventions. In this article, we have reviewed combinations of different pharmacologic treatments, combinations of non-pharmacologic interventions, and combined pharmacologic and non-pharmacologic interventions for TBI. Both preclinical and clinical studies have been included. While promising results have been found in animal models, clinical trials of combination therapies have not yet shown clear benefit. This may possibly be due to their application without consideration of the evolving pathophysiology of TBI. Improvements of this paradigm may come from novel interventions guided by multimodal neuromonitoring and multimodal imaging techniques, as well as the application of multi-targeted non-pharmacologic and endogenous therapies. There also needs to be a greater representation of female subjects in preclinical and clinical studies.

Severe asthma patients are at increased risk of major exacerbations and they need to be monitored regularly. The COVID-19 pandemic has impressively impacted on the health care resources. The telemedicine approach applied to the follow-up of asthmatic patients has been proved to be effective in monitoring their disease and adherence to the therapy. The aim of our study was to investigate the satisfaction of severe asthma patients, before the activation of a telemedicine management complemented by a standard of care. An ad hoc questionnaire was developed and sent by e-mail to 180 severe asthma patients. Most of subjects (82%) were confident with the idea of doing self-measurements and self-managing their disease; 77% of subjects favoured to carry out virtual visit and telemedicine. 93% of patients considered easy the self-injection therapy. 94% of subjects felt safe and 93% were not worried while self-administering. Only mild adverse events were reported in 22% subjects after self-administration. Our results showed an agreement between what is considered necessary and practicable by healthcare personnel and what is perceived by the severe asthma patients, in terms of treatment and monitoring of the disease with Telehealth. Biologics have a safety profile and can be easily self-administred at home

Background Radial extracorporeal shock wave therapy (rESWT) is an attractive, non-invasive therapy option to manage fracture nonunions of superficial bones, with a reported success rate of approximately 75%. Using zebra mussels (Dreissena polymorpha), we recently demonstrated that induction of biomineralization after exposure to focused extracorporeal shock waves (fESWs) is not restricted to the region of direct energy transfer into calcified tissue. This study tested the hypothesis that radial extracorporeal shock waves (rESWs) also induce biomineralization in regions not directly exposed to the shock wave energy in zebra mussels. Methods Zebra mussels were exposed on the left valve to 1000 rESWs at different air pressure (between 0 and 4 bar), followed by incubation in calcein solution for 24 hours. Biomineralization was evaluated by investigating the fluorescence signal intensity found on sections of the left and right valves prepared two weeks after exposure. Results General linear model analysis demonstrated statistically significant (p < 0.05) effects of the applied shock wave energy as well as of the side (left/exposed vs. right/unexposed) and the investigated region of the valve (at the position of exposure vs. positions at a distance to the exposure) on the mean fluorescence signal intensity values, as well as statistically significant combined energy × region and energy × side × region effects. The highest mean fluorescence signal intensity value was found next to the umbo, i.e., not at the position of direct exposure to rESWs. Conclusions As in the application of fESWs, induction of biomineralization by exposure to rESWs may not be restricted to the region of direct energy transfer into calcified tissue. Furthermore, the results of this study may contribute to better understand why the application of higher energy flux densities beyond a certain threshold does not necessarily lead to higher success rates when treating fracture nonunions with extracorporeal shock wave therapy.

In this study, we propose a radiomics-clinical probability weighted model for the prediction of prognosis for NSCLC. The model combines radiomics features extracted from RT planning images with clinical factors such as age, gender, histology, and tumor stage. CT images with radiotherapy structures of 422 NSCLC patients were retrieved from The Cancer Imaging Archive (TCIA). Radiomic features were extracted from gross tumor volume (GTV). Five machine learning algorithms, namely decision trees (DT), random forests (RF), extreme boost (EB), support vector machine (SVM) and generalized linear model (GLM), were optimized by a voted ensemble machine learning (VEML) model. A probabilistic weighted approach is used to incorporate the uncertainty associated with both radiomic and clinical features and to generate a probabilistic risk score for each patient. The performance of the model is evaluated using a receiver operating characteristic (ROC). Radiomic model, clinical factors model and combined radiomic-clinical probability weighted model demonstrated good performance in predicting NSCLC survival with AUC of 0.941, 0.856 and 0.949 respectively. The combined radiomics-clinical probability weighted enhanced model achieved significantly better performance than radiomic model in 1-year survival prediction (chi-square test, p<0.05). The proposed model has the potential to improve NSCLC prognosis and facilitate personalized treatment decisions.

Personal protective equipment (P PE) rules must be respected and followed to the letter of healthcare professionals in Cameroon to avoid the transmission of infectious diseases. This research proposes solutions to the problems of non-adherence and non-compliance among healthcare workers in Cameroon towards PPE rules. Inadequate access to suitable PPE, discomfort when wearing PPE during poor quality, and a lack of training on correct PPE use are just a few of these obstacles amongst HCWs in Cameroon. Hospitals and healthcare facilities should prioritize offering thorough instruction on PPE use and pinpoint the need to adhere consistently to PPE rules to remove these obstacles. They should also ensure that all healthcare personnel have access to and a sufficient supply of the proper PPE. Through the organization of impromptu visits by surveillance teams to identify areas of support and training, there is a need for assistance from government bodies and public health groups in creating awareness of the security value of PPE use among healthcare professionals. There is a lack of PPE in health care settings in rural areas in Cameroon, thus a need for an adequate supply. Then can we put appropriate PPE policies and practices for HCWs in Cameroon, as they will keep to it.Healthcare professionals in Cameroon must comprehend that following PPE standards protects not just their selves from diseases but also their patients, coworkers, and communities. We are accountable for ensuring everyone's safety and well-being, and adhering to PPE regulations is an essential first step.

We aimed to explore symptoms severity and adherence to therapy for patients with myelofibrosis treated with ruxolitinib in Bulgaria. It is a prospective, non-interventional study performed at the Specialized hospital for active treatment of hematological diseases in Sofia during 2022 - 2023. Date of diagnosis, demographic characteristics, clinical indicators, ruxolitinib dose, and other data points were collected. Clinical indicators were assessed at baseline, in the middle and at the end of observation. Severity of symptoms was measured with MPN-SAF TSS and adherence to therapy with the Morisky 4 questionnaire 6 times during the observation. The mean age of diagnosis was 58.5 years, with the average duration of disease of 3 years. Pa-tients’ laboratory results were within physiological ranges, with spleen size experiencing a con-stant decrease. The average value for the severity of the symptoms per MPN-SAF TSS results decreased significantly, indicating better disease control. The average adherence to therapy did not change and remained high at around 9 points, except for one patient. In conclusion the treatment of myelofibrosis patients with ruxolitinib decreased symptoms se-verity and spleen size. Patients were adherent to the therapy over the observed period but as treatment duration increases the risk of adherence decreasing.

It is not new in medical history to propose a global concern to be classified as a disease. Defining a concern into disease allows to assign ethical responsibilities to develop powerful and effective interventions. It also allow to appropriate distribute the resources uniformly economically and morally. In 2003, World Health Organization report stated that 30-50 % of patients do not take their medications as prescribed associated with morbidity, mortality and health cost. It was considered a global concern, however, irrespective of decades of researches conducted on medication adherence, we are still unable to state that medication adherence issues are being resolved. In this review, we have described few apprehensions in current understandings of medication adherence that have limited its research. We have also proposed medication adherence as disorder and provided its’ definition and classification

Chronic conditions like type 2 diabetes mellitus (T2DM), arterial hypertension (HTN), and obesity are major global health issues, causing significant morbidity and mortality. In Latin America, these conditions contribute to millions of premature deaths annually, posing challenges exacerbated by limited healthcare access and poor primary care quality, particularly in Mexico. Complementary medicine presents a potential solution, offering minimally invasive techniques to improve physical, mental, and spiritual well-being. Effective treatment adherence, crucial for positive outcomes, is influenced by self-efficacy, the ability to manage one's behavior in response to medical conditions. However, treatment adherence rates remain low, indicating a pressing public health concern. This study aimed to explore how perception of complementary medicine and treatment adherence predict self-efficacy among individuals with chronic conditions in Mexico. Analyzing data from 113 participants revealed significant correlations between variables, with treatment adherence positively associated with self-efficacy and perception of holistic medicine negatively correlated with self-efficacy. Regression analysis showed that incorporating perception of complementary medicine and treatment adherence significantly explained self-efficacy levels, suggesting the potential of complementary therapies in holistic healthcare approaches. However, collinearity between variables highlights the need for further research to better understand these relationships and their implications for improving healthcare outcomes in Mexico. Integrating complementary therapies with conventional treatments could enhance overall well-being and treatment adherence, offering promising avenues for addressing chronic conditions in the region. These findings underscore the importance of comprehensive healthcare approaches that integrate both conventional and complementary modalities to optimize health outcomes and quality of life for individuals with chronic conditions in Mexico and beyond.

Abstract: Objective: This study aimed to estimate adherence to methotrexate in patients with rheumatoid arthritis and identify specific nonadherence risk factors. Methods: A cross-sectional study included 111 patients (age mean 56.2±10.6 years, 78.4% female, and disease duration mean 6 (3-13) years). Three adherence self-assessment questionnaires were used: the Compli-ance-Questionnaire-Rheumatology (CQR19), the Medication Adherence Reports Scale (MARS-5), and the Visual Analogue Scale (VAS). We also collected demographic data, disease and treatment characteristics, and anxiety/depression estimation results (Hospital Anxiety and Depression Scale- HADS). Results: Adherence was identified in 48.6% of patients (COR19), 70.3% (MARS-5), and 82.9% of patients in the VAS questionnaire. All three questionnaires displayed a significant positive mutual correlation: CQR19 with MARS-5 and VAS (r =0.364, r=0.329 respectively, p<0.001 for both), between VAS and MARS-5 score (r=0.496, p<0.001). A significant positive prediction was shown for urban residence (0.347 (0.134-0.901), p=0.030), using the MARS-5 scale, female sex (0.264 (0.095-0.730), p=0.010) according to CQR19 and for a dose of methotrexate (0.881 (0.783-0.992), p=0.036) in VAS scale, while negative prediction were shown for comorbidity number (3.062 (1.057-8.874), p=0.039), and depression (1.142 (1.010-1.293), p=0.035) using MARS-5 scale and for older age (1.041 (1.003-1.081), p=0.034) according to CQR19. The use of steroids was a significant positive predictor in all three questionnaires and remained an independent predictor for metho-trexate adherence in multivariant logistic regression. Conclusion: We showed nonadherence to methotrexate in a significant number of patients using all three questionnaires. Concomitant steroid therapy emerged as an independent positive predictor for adherence.

Two decades after the antiretroviral therapy (ART) introduction, several challenges still prevail in maintaining people living with HIV (PLHIV), even with "Test and Treat" and/or "Rapid Start of ART" initiatives, as well as the scale-up of ART worldwide to promote access and adherence to treatment. This review examined articles on ART adherence in Africa between 2016 and 2023, published in English and indexed in PubMed. A total of 16 articles out of 2415 were eligible and included for analyses. Overall, ART adherence rates in SSA regions ranged from 43% to 84%. Rates in the centre of the SSA region ranged from 58% to 80%, in the north from 50% to 83%, in the south from 77% to 84%, in the west from 43% to 60% and in the east from 69% to 73%. Most African countries use the self-report to assess treatment adherence, although unreliable. The main factors with negative influence on ART adherence were comorbidities, lack of motivation, socioeconomic difficulties or side effects. Conclusion: Adherence to ART is a good indicator for controlling the spread of HIV. It is important to overcome the barriers that make it difficult to comply with ART and reinforce the factors that facilitate the accession of medication.

Background: Clean cookstove interventions can theoretically reduce exposure to household air pollution and benefit health, but this requires near-exclusive use of the stoves, with simultaneous disuse of traditional stoves. Previous cookstove trials have reported low adoption of new stoves and/or extensive continued traditional stove use. Methods: The Household Air Pollution Intervention Network (HAPIN) trial randomized 3195 pregnant women in Guatemala, India, Peru, and Rwanda either to a liquefied petroleum gas (LPG) stove and fuel intervention (n = 1590) or to control (n = 1605). The intervention consisted of an LPG stove and two initial cylinders of LPG, free fuel refills delivered to the home, and regular behavioral messaging. We assessed intervention fidelity (delivery of the intervention as intended) and adherence (intervention use) through the end of gestation, as relevant to the first primary health outcome of the trial: infant birth weight. Fidelity and adherence were evaluated using stove and fuel delivery records, questionnaires, visual observations, and temperature-logging stove use monitors (SUMs). Results: 1585 women received the intervention, at a median (interquartile range) of 8.0 (5.0–15.0) days post-randomization and gestational age of 17.9 (15.4–20.6) weeks. Over 96% reported cooking exclusively with LPG at two follow-up visits during pregnancy. Less than 4% reported ever running out of LPG. Complete abandonment of traditional stove cooking was observed in over 67% of intervention households. 31.4% removed their traditional stoves upon receipt of the intervention, and among those who retained traditional stoves, the majority did not use them: traditional stove use was detected via SUMs on a median (interquartile range) of 0.0% (0.0%, 1.6%) of follow-up days (median follow-up = 134 days). Conclusions: Fidelity of the HAPIN intervention, as measured by stove installation, timely ongoing fuel deliveries, and behavioral reinforcement as needed, was high. Exclusive use of the intervention during pregnancy was also high.

I. Introduction: Adherence to ART reduces morbidity and mortality among PLHIV by suppression of viral replication, restoration and preservation of immune function. However, poor adherence may lead to treatment failure and death. PLHIV have high probability of treatment interruptions due to lockdowns related to COVID-19 protocol. Mortality rate is higher among COVID-19 patients with HIV than those with COVID-19 only. This led to determination of the barriers to antiretroviral medication adherence in PLHIV at the time of COVID-19 pandemic and seek significant association between identified HIV treatment barriers and socio-demographic characteristics. II. Methods: A cross-sectional study using online survey questionnaire was distributed via social media. Sample size was computed using Open Epi software. Data was analyzed using Stata software. Categorical variables and quantitative data were summarized using frequencies and percentages, and mean and standard deviation respectively. Chi-square test or Fisher’s exact test, whichever is more appropriate, was used to determine association between socio-demographic characteristics and HIV treatment barriers. III. Results: There is a total of 116 respondents, 115 were males, homosexual (59.5%), with mean age of 30.25 years old (SD = 6.22) and majority (53.4%) were from NCR. The most common HIV treatment barriers reported by PLHIV in accessing treatment and care were unavailability of transportation and cost of courier services for ARV delivery (62.1%), location of treatment hubs (52.6%) and financial assistance (37.9%). IV. Conclusion: There is significant association between location of treatment hubs and respondents who finished college/graduate studies; checkpoints and crossing borders and: 1. respondents from Northern Luzon, 2. unemployment; financial assistance and: 1. Respondents 18 to 25 years old, 2. unemployment, 3. respondents who finished elementary/high school; psychosocial support and: 1. Respondents from NCR, 2. Respondents 26 to 30 years old;

Food Neophobia (FN), defined as the reluctance to eat new or unfamiliar foods, mainly concerns fruit, vegetables, and legumes, typical of the Mediterranean Diet (MD). Considering these premises, this study aimed to clarify the relationship between FN and AMD in a sample of Italian children and their association with some socio-demographic factors and children's nutritional status. A sample of 288 children aged 3-11 years, participated to an assessment carried out with a questionnaire evaluating FN and AMD, respectively with Child Food Neophobia Scale (CFNS) and the KIDMED Test. Most of the sample showed an intermediate (67.3%) or high level of FN (18.1%) with high rates among 6-11 years old children (63.9%) and especially in only-child (50%). The AMD was mostly low (29.5%) or medium (54.8%) and reached lower levels among higher neophobic children (51.9%; p value &lt; 0.05). Present results confirm the study hypothesis that FN is a driver of MD abandonment and show the positive effects on children's eating habits of having siblings. Finally, this study proves the relevance of adopting effective feeding strategies against FN to avoid its maintenance in adulthood and detrimental effects on future overall health and well-being.

Abstract Diabetes mellitus (DM) is an independent risk-factor for cardiovascular diseases. Plant-based dietary-patterns have been shown to positively impact the effects this cardiovascular risk-factor. The purpose of this study is to investigate the association of adherence to moringa, plantains, moringa-plantain combined, and other plant based dietary-patterns with glycemic-control among persons with type-2-diabetes Mellitus (T2DM). Facility-based cross-sectional-study was conducted among 530 T2DM patients in Ghana. Structured-questionnaires were used to collect demographic, anthropometric, and clinical variables. Adherence to plant-based dietary-patterns were assessed with 24-hour dietary-recall questionnaire. SPSS version-22 was used in data analysis. BMI, HbA1c%, HDL-cholesterol and LDL-cholesterol were significantly correlated with adherence to plant-based dietary-patterns (p-value < 0.05). After adjusting for confounders, adherence to: Plantain diets, standardized regression coefficient β (95%CI): -0.098 (-0.321, -0.022), Yam, β (95%CI): 0.148 (0.066, 0.496), Moringa diets β (95%CI): -0.095 (-0.325,-0.011) and Bean-diets β (95%CI): -0.112 (-0.577-.007) were significantly associated with glycemic control. Also adherence to: Plantain-moriga combined diets β (95%CI): -0.406 (-0.413, -0.049) and Plantain-beans combined diets β (95%CI): -0.128 (-0.188, -0.038) were significantly associated with glycemic control. Adherence to Plantain, Yam, Beans, Plantain-moriga combined diets, and Plantain-beans combined diets could be associated with glycemic control. Keywords: Diabetes mellitus, Adherence, Moringa, Plantain, Glycemic control, Ghana.

Primary and secondary cardiovascular prevention is less effective than expected due to the concern about polymedication by professionals and the lack of patient adherence to medications prescribed in the medium and long term. Polypills have been presented as a possible solution. A comprehensive bibliographic review is presented about polypills as mechanisms for facilitating adherence and a proposed guide for the use of polypills for the prevention of cardiovascular risk. 41 articles were included, showing options for the polypill as a method of primary and secondary cardiovascular prevention.The polypill increases therapeutic adherence in the medium and long term, also increasing the therapeutic results compared to the administration of the various drugs separately. Based on the evidence, a flow diagram is proposed for the prescription of a polypill.Polypills increase the effectiveness and adherence of patients to primary and secondary cardiovascular prevention programs, without increasing the cost of the intervention. The use of a polypill in cardiovascular prevention can be effective as a prescription tool.

Worldwide epidemiological data indicates insufficient diagnosis of diabetes as an increasing problem of public health. Searching for solutions in this disadvantageous situation, occupational medicine health services seem to open up a unique opportunity to recognize some abnormalities in early steps, especially among the asymptomatic working-age population. 316 workers underwent obligatory prophylactic examinations. In patients with twice assayed FGL ≥ 126 mg/dl (7.0 mmol/l) the additional intervention was implemented, including further diagnostic process and therapy in General Practice (GP), followed by examination by an occupational health specialist within 3 months. The diagnosis of previously unknown diabetes was established among 2.5% of examined workers. All patients referred to the GP due to detected glycaemia impairment visited their doctor and finished the diagnostic process, took up therapy constrained by the occupational health physician to show the effects of intervention within 3 months. Prophylactic medical check-ups allow improved compliance and medical surveillance over glycaemia impairment in patients with prediabetes states, unknown diabetes or uncontrolled clinical course of diabetes. Considering fasting glucose level during mandatory prophylactic examination helps effective prevention of diabetes and its complications and thus give public health system benefits.

Different prognostic scores have been applied to identify patients with non-small cell lung cancer who have a higher probability of poor outcome. In this study we evaluated whether Naples Prognostic Score, a novel index which considers both inflammatory and nutritional values, was associated with long-term survival. The study is a retrospective propensity score matching analysis of patients who underwent curative surgery for non-small cell lung cancer from January 2016 to December 2021. The score considered four pre-operative parameters: neutrophil to lymphocyte ratio, lymphocyte to monocyte ratio, serum albumin and total cholesterol. Kaplan-Meier method and Cox regression analysis were performed to evaluate the relation between the score and disease-free survival, overall survival and cancer-related survival. A total of 260 patients were selected for the study, reduced to 154 after propensity score matching. Post-propensity Kaplan-Meier analysis showed a significant correlation between Naples Prognostic Score and overall survival (p=0.018) and cancer-related survival (p=0.007). Multivariate Cox regression analysis further validated the score as an independent prognostic indicator for both these survivals (p=0.007 and p=0.010 respectively). Naples Prognostic Score proved to be an easily achievable prognostic factor of long-term survival in patients with non-small cell lung cancer after surgical treatment.

Adherence is vital for medicine to have an effect, yet adherence is considered to be low. However, research into adherence tends to focus on quantitative analysis of performance, something which fails to perceive how people are adherent in their many different environments. As a contribution to gaining a deeper understanding, interviews were held with 30 individuals in UK, Egypt, Kazakhstan and 6 countries in sub-Saharan Africa to understand their perceptions on adherence for a range of drugs, and these were compared with an existing well-regarded list. New reasons for non-adherence were discovered, and a new viewpoint on adherence derived which considers adherence to be a single act and therefore as an individual opportunity to be adherent, permitting greater focus on the enablers and inhibitors of adherence at a point in time.

Adherence with multidrug therapy (MDT) is one of the keys to successful treatment of leprosy. In order to understand the treatment behavior, reasons for non-adherence, and efforts to improve medication adherence, it is necessary to use a valid and reliable instrument to measure adherence to MDT in multibacillary leprosy patients on regular basis. This study used a mixed method de-sign. The instrument development phase involved 10 experts using 4 rounds of Delphi method. Assessment items that are considered relevant are those that meet 4-5 Likert scale by a minimum of 75% of experts or meet assessment score >3.75. We did the pilot testing and the questionnaire was revised if invalid. After obtaining a valid and reliable instrument, it was tested to 100 sub-jects in 4 health centers. For internal validity test, 9 valid assessment items were obtained, with the correlation coefficient values of each item >0.3, and -Cronbach's reliability of 0.723. The instru-ment produced had sensitivity of 88.46% and specificity of 78.37%. From 100 subjects enrolled, 61% had good adherence and 39% had poor adherence based on questionnaire assessment. A valid and reliable questionnaire for evaluating adherence with MDT in Indonesian patients has been composed.

Objective: To explore the inter-rater reliability of the Measurement Of adherence Via Exercise Demonstration (MOVED) adherence tool. Design: Reliability study of a patient adherence measurement tool.Setting: Simulated physiotherapist-patient consultations. Participants: Sixteen experienced physiotherapists rated patient adherence to exercise. Interventions: N/A Main Outcome Measure: Inter-rater reliability of MOVED.Methods: The MOVED tool consists of two parts. Part one asks patients to self-report their adherence to exercise dose (including number of completed sessions, sets and repetitions in the last seven days). Part two asks patients to demonstrate each exercise. Component scores are totalled to give an overall level of patient adherence to each exercise.Participants were provided with a copy of five physiotherapist-prescribed exercises. Participants were then shown five corresponding video vignettes of simulated physiotherapist-patient consultations where patients were asked to self-report exercise frequency, sets and repetitions and demonstrate each exercise within the context of a consultation. Participants were asked to rate the level of patient adherence to each of the five exercises using the MOVED tool. Inter-rater reliability of MOVED scores was assessed using Intraclass Correlation Coefficient (ICC) and 95% Confidence Intervals. Results: The ICC of part one (self-report) was .90 (95%CI .74-.98), part two (demonstration) was .98 (95%CI .94-.99) and total score was .96 (95%CI .88-.99), demonstrating excellent inter-rater reliability. Conclusion: The MOVED tool, which can highlight whether patients are adhering to exercise technique as well as exercise dose, may provide clinicians and researchers with a more robust measure of exercise adherence when compared with other measures currently available.

This study aimed to investigate the knowledge of patients with hypertension about their condition, adherence to antihypertensive medication, and the factors influencing it. A cross-sectional study was conducted in two cardiology outpatient clinics of two tertiary hospitals, in Greece. The study included 188 patients diagnosed with hypertension. The patient’s knowledge about their disease and adherence to medication were assessed by using the HK-LS and A-14 scales, respectively. Patients had sufficient knowledge levels about their disease, but significantly low levels of adherence to medication. Patients with higher knowledge levels were more adherent to medications [r(188) = 0.885, p &lt; 0.001]. By using multivariate analysis, higher age (p = 0.018), residence in a more populous area (p = 0.041), more years with the disease (p = 0.012), and a lower number of medications (p = 0.03) were associated with higher levels of knowledge. Conversely, younger age (p = 0.036), lower educational levels (p = 0.048), fewer years with the disease (p = 0.001), and a higher number of medications (p = 0.003) were associated with lower adherence to medication. The Greek patients' hypertension knowledge was sufficient, however, adherence to medication was significantly low. Healthcare managers could utilize our findings to design targeted interventions for improving adherence to medication for these patients.

Worldwide, diarrhoea in children under-five years of age is the second leading cause of death. Despite having high morbidity and mortality, diarrhoeal diseases can be averted by simple and cost-effective interventions. The Integrated Management of Childhood Illness (IMCI) has proposed the use of Oral Rehydration Salt (ORS) and zinc together with adequate food and fluid intake for the management of acute non-dysenteric watery diarrhoea in children. In the past, few studies examined the determinants of adherence to diarrhoea case management. Therefore, this study measured the determinants of therapeutic and dietary adherence to diarrhoea case management using the third and fourth wave of Pakistan Demographics & Health Surveys (PDHS) datasets. Data from 4,068 children between 0 to 59.9 months with positive history of diarrhoea were included, while data on children with dysentery, severe dehydration, and co-morbid condition was excluded. This study reported therapeutic adherence in less than 10% of children in Pakistan, while dietary adherence was reported in 39.2% of children (37.7% in 2012-2013 ~ 40.7% in 2017-2018). A significant improvement in therapeutic (0.8% in 2012-2013 ~ 8.1% in 2017-2018) and dietary adherence (37.7% in 2012-2013 ~ 40.7% in 2017-2018) was reported in the 2017-2018 survey, compared to the 2012-2013 survey. In general, children over the age of one year (compared to children <1 year) and of the richer/richest socioeconomic class (compared to poorest/poorer socioeconomic class) have showed higher therapeutic and dietary adherence. Therapeutic and dietary adherence among diarrhoeal children can be improved by increasing the awareness and accessibility of ORS, zinc, and essential foods.

Young people living with perinatal infections of Human Immunodeficiency Virus (YLPHIV) face a chronic disease, with treatment including adherence to life-long antiretroviral treatment (ART). The aim of this QES was to explore adherence to ART for YLPHIV as an assemblage within the framework of the BPS model with a new materialist perspective. We searched up to November 2021 and followed the ENTREQ and Cochrane guidelines for QES. All screening, data extraction and critical appraisal was done in duplicate. We analysed and interpreted the findings innovatively, by creating images of meaning, a storyboard, and storylines. We then reported the findings in a narrative first person story. We included 47 studies and identified 9 storylines. We found that treatment adherence has less to do with humans’ preferences, motivations, needs and dispositions, and more to do with how bodies, viruses, things, ideas, institutions, environments, social processes, and social structures assemble. This QES highlights that adherence to ART for YLPHIV is a multisensorial experience in a multi agentic world. Future research into rethinking the linear and casual inferences we are accustomed too in evidence-based health care is needed if we are to adopt multidisciplinary approaches to address pressing issues such as adherence to ART.

Androgen deprivation therapy (ADT) for prostate cancer treatment is associated with adverse physiological changes, however exercise can improve outcomes. This systematic review and meta-analysis aimed to determine exercise intervention adherence, and its effects on physiological outcomes in men diagnosed with prostate cancer undergoing ADT. Uniquely, this review incorporates a meta-aggregation of qualitative data, providing perspectives from the men’s experiences. A systematic review and meta-analysis were completed following PRISMA Guidelines. Databases (CINAHL, Cochrane, PubMed) were searched for studies using “prostate cancer”, “exercise intervention”, and “androgen deprivation therapy”. Quantitative randomised controlled trials describing adherence to exercise interventions were selected, with qualitative articles selected based on descriptions of experiences around participation. Subgroup meta-analyses of adherence, exercise mode, and intervention duration were completed for quality of life, aerobic fitness, fatigue, and strength. Articles (n=64) articles were identified, with 29 (n=23 quantitative; n=6 qualitative) articles from 25 studies included. Exercise had no effects (p&lt;0.05) on quality of life and fatigue. Significant effects (all p&lt;0.05) were observed for aerobic fitness, and upper- and lower-body strength. Adherence to exercise-based interventions was 80.38%, with improvements observed in aerobic fitness and strength. Subgroup analysis revealed exercise adherence impacted fatigue and strength, with greater improvements observed in programs &gt;12-weeks.

Every year, General Practitioners (GPs) see over 13 million patients for dermatological concerns making dermatology the highest referring speciality. Artificial Intelligence (AI) systems could improve system efficiency by supporting clinicians in making appropriate referrals, but they are, like human clinicians, imperfect and there may be a trade-off between sensitivity and specificity that is likely to result in false negatives. In this paper, a study is presented to explore two areas. Firstly, the aptitude of GPs to trust appropriately (or not trust) the outputs of a fictitious AI-based decision support tool when assessing skin lesions. Secondly, to identify which individual characteristics could make GPs less prone to adhere to erroneous diagnostics results and to refrain from passive adherence to AI. Findings suggest that when the AI is correct, there is a positive effect on GPs’ performance and confidence suggesting the potential to reduce referrals for benign lesions. However, when an inexperienced GP is presented with a false-negative result, they may passively deviate from their initial clinical judgement to accept the wrong diagnosis provided. AI systems will have a false-negative rate and, when adopting new technologies, this needs to be acknowledged and fed into risk-benefit discussions and considerations around additional safety measures.

Background: To determine vitamin D supplementation frequency among infants, factors that influence adherence, and reasons for discontinuation of initiated vitamin D. Methods: This cross-sectional study was conducted using a questionnaire administered to the mothers via a face-to-face interview on 560 infants aged from 1 to 24 months admitted to outpatient clinics from June to December 2017. Results: A total of 351 infants were administered vitamin D, and the rate of supplementation in the first year of life was 83%, while it was only 28% between 13 and 24 months. The rate of vitamin D supplementation was higher among infants who were exclusively formula-fed (p<.05). When the data were analyzed using logistic regression analysis, only visit family physicians seems to be a statistically significant independent variable in increasing supplementation (p<.05). Compared with family refusal, the rate of discontinuation of vitamin D by the healthcare providers was higher after the first year of life (p<.05). The rates of vitamin D discontinuation by healthcare providers, especially by nurses who considered the duration of supplementation adequate, were statistically significantly higher when compared with the fontanel closure and other reasons (p<0.05). Conclusions: The rate of vitamin D supplementation was higher among families who visited family physicians, which suggests the importance of well-baby visits. Since vitamin D supplementation was less common among exclusively breastfed infants, mothers should be educated. Healthcare professionals need further education about the importance of vitamin D supplementation and indications for discontinuation.

Type 2 diabetes mellitus (T2DM) is a common metabolic disease characterised by insulin resistance and elevated blood glucose levels, affecting millions of people worldwide. T2DM patients with dyslipidaemia have an increased risk of cardiovascular disease (CVD). A complex interplay of risk factors such as hyperglycaemia, dyslipidaemia, hypertension, obesity, inflammation and oxidative stress favour the development of atherosclerosis, a central mechanism in the pathogenesis of cardiovascular disease. Dyslipidaemia, a hallmark of T2DM, is characterised by elevated triglycerides, decreased high-density lipoprotein (HDL) cholesterol and the presence of small, dense low-density lipoprotein (LDL) particles, all of which promote atherosclerosis. In this article, we have attempted to present various treatment strategies that include pharmacological interventions such as statins, ezetimibe, PCSK9 inhibitors, fibrates and omega-3 fatty acids. We have also tried to highlight the pivotal role of lifestyle modifications, including physical activity and dietary changes, in improving lipid profiles and overall cardiovascular health in T2DM patients. We have also tried to present the latest clinical guidelines for the management of dyslipidaemia in T2DM patients. In conclusion, the treatment of dyslipidaemia in T2DM patients is of great importance as it lowers lipid particle levels, slows the progression of atherosclerosis and ultimately reduces susceptibility to cardiovascular disease.

The research and development of non-viral gene therapy has been extensive over the past decade and has received a big push thanks to the successful approval of non-viral gene therapy products in recent times. Despite these developments, gene therapy applications in cancer have been limited. One of the main causes of this has been the imbalance in development of delivery vectors as compared to nucleic acid payloads. This paper reviews non-viral vectors that can be used to deliver nucleic acids for cancer treatment. It discusses various types of vectors and highlights their current applications. Additionally, it also discusses perspective on regulatory landscape to facilitate commercial translation of gene therapy.

Pesticides are widely used in agriculture as a pest control strategy. Despite the benefits of pesticides on crop yields, the persistence of chemical residues in soil have an unintended impact on non-targeted microorganisms. In this study, we evaluated the impact of the combined fungicide (difenoconazole, epoxiconazole, and kresoxim-methyl) on fungal and bacterial communities of Phaeozem. In the fungicide-treated soil, the Shannon index of both fungal and bacterial communities was decreased, while Chao1 index did not differ compared to the control soil. Among bacterial taxa, the relative abundance of Athrobacter, Sphingomicrobium, and Sphingomonas increased in fungicide-treated soil due to their ability to utilize fungicides and other toxic compounds. Rhizopus and plant-beneficial Chaetomium were the dominant fungal genera, which increased 2-4 times in the fungicide-treated soil, while the relative abundance of Mortierella and Talaromyces decreased. Fusarium acuminatum was the most abundant phytopathogenic fungus that causes root rot disease of wheat, but applied fungicide treatment decreased their diversity in the soil 2 times, which is consistent on the observed plants.

The incidence of hepatocellular carcinoma (HCC) is increasing and 40% of patients are diagnosed at advanced stages. Over the past 5 years, the number of clinical available treatments have dramatically increased for HCC, making patient management particularly complex. Immune checkpoint inhibitors (ICIs) have improved the overall survival of patients showing a durable treatment benefit over time, and a different response pattern with respect to tyrosine kinase inhibitors (TKIs). Although improved survival in responder cases, a sizeable group of patients are primary progressors or are ineligible for immunotherapy. Indeed, patients with non-viral etiologies, such non-alcoholic steatohepatitis (NASH), and alterations in specific driver genes might be less responsive to immunotherapy. Therefore, improving the comprehension of mechanisms of drug resistance and identifying biomarkers informative of the best treatment approach are required actions to improve patient survival. Numerous evidence indicated non-coding RNAs (ncRNAs) as pivotal players in cancer. Molecular mechanisms through which ncRNAs exert their effects in cancer progression and drug resistance have been widely investigated. Nevertheless, there are no studies summarizing the synergistic effect between ncRNA-based strategies and TKIs or ICIs in the preclinical setting. This review aims to provide up-to-date information regarding the possible use of ncRNAs as therapeutic targets in association with molecular targeted agents and immunotherapies and as predictive tools for the selection of optimized treatment options in advanced HCCs.

Respiratory allergic diseases, affect over 500 million people globally and pose a substantial burden in terms of morbidity, mortality, and healthcare costs. Restrictive factors such as geographical disparities, infectious pandemics, limitations in resource, and shortage of allergy specialists in underserved areas, impede effective management. Moreover, the well-established suboptimal adherence in patients with respiratory allergies, contribute further to the accelerated loss of disease control. Telemedicine encompasses real-time visits, store-and-forward options triage, and computer-based technologies for establishing and efficient doctor-patient communication. Recent advances in digital technology, including designated applications, informative materials, digital examination devices, wearables, digital inhalers, and integrated platforms, facilitate personalized and evidence-based care delivery. The integration of telemonitoring in respiratory allergy care has shown beneficial effects in disease control, adherence, and quality of life. While the COVID-19 pandemic accelerated the adoption of telemedicine, certain concerns regarding technical requirements, platform quality, safety, reimbursement, and regulatory considerations remain unresolved. Challenges in telemonitoring implementation further include ensuring effective doctor-patient collaboration, addressing privacy concerns, and establishing cost-effective models. The integration of artificial intelligence (AI) in telemonitoring applications holds promise for data analysis, pattern recognition, and personalized treatment plans. Striking the balance between AI-enabled insights and human expertise is crucial for optimizing the benefits of telemonitoring. This overview reports the up- to- date telemedicine approaches in managing patients with respiratory allergies. While telemonitoring exhibits potential in enhancing patient care and healthcare delivery, critical considerations have to be addressed in order to ensure the successful integration of telemonitoring into the healthcare landscape.

Outdoor exercise is beneficial for psychophysical well-being. Limited studies have compared outdoor and virtual reality (VR) indoor physical activities, especially in coastal settings. Therefore, this study aimed to assess the impact of outdoor coastal walking and indoor walking in a VR simulation with a similar environment on physiological and psychological variables in healthy adults. Twenty-six subjects (14M and 12F; age 25.2 ± 2.5 years) voluntarily participated in this crossover randomized controlled and counterbalanced study and were allocated under three conditions: VR indoor walking (INVR), outdoor walking (OUT) and standard indoor walking (IN). IN and INVR conditions were performed on a treadmill (speed 4.5 Km/h) and the OUT was per-formed on a seaside pedestrian road. The same outdoor environment was displayed in the visor during the INVR. Heart rate (HRmean/max), Physical Activity Enjoyment (PACES-It) and State of Mindfulness for Physical Activity (SMS-PA) were assessed at the end of each condition. The OUT condition showed significantly greater PACES-It scores and HRmean than IN and INVR (p<0.001) and greater SMS-PA scores and HRmax than IN (p<0.01 and p<0.05, respectively). No significant dif-ferences were found between OUT and INVR regarding HRmax and SMS-PA scores (p>0.05). Findings suggest that physical activity in an immersive technology may lead to physiological loads comparable to the outdoor environment. OUT is more enjoyable than IN and INVR but exhibits a mindfulness response comparable to INVR. Therefore, INVR could be an alternative to OUT for those who cannot engage in outdoor activities for various reasons.

Purpose: Determine the internal consistency and reproducibility test-retest of the Barrier Scale for Cardiac Rehabilitation (BSCR) in Colombian population. Methods: 190 patients (67% men, average age = 65 ± 12 years) completed the scale in two moments, with an average of eight days between applications. Cronbach's Alpha and Intraclass Correlation (ICC) coefficients were calculated. Results: The internal consistency of the Colombian version of the BSCR was good (Cronbach's alpha = 0.85). The ICC of the instrument was 0.69 (95% CI 0.61-0.76), 0.78 (95% CI 0.71-0.84) when used in the interview type, and 0.47 (95% CI 0, 21-0.67) when it was self-completing. Conclusions: The EBRC has an acceptable reliability in the Colombian population, however, its reproducibility decreases when it is self-directed. Identifying barriers using this scale will allow developing strategies to increase participation and adherence to cardiac rehabilitation programs focused on the real needs of patients.

Damage and fibre misalignment of woven fabrics during discontinuous polymer processing remain challenging. To overcome these, a promising switchable elastomeric adherence gripper is introduced here. The inherent surface tackiness is utilized for picking and placing large sheets. Due to the elastomer’s viscoelastic material behavior, the surface properties depend on loading speed and temperature. Different peeling speeds result in different adherence strength of an interface between the gripper and the substrate. This feature is mechanically characterized and the viscoelastic behavior of the stamp is examined. Based on this experimental characterization, an empirical model is proposed. Furthermore, a discussion of the applicability and limitation of the elastomeric gripper is given.

The aim of this cross-sectional study was to assess the perceived medication-related burden among patients with multiple non-communicable diseases (NCDs), and to investigate the association between perceived burden and adherence to medication therapy. Medication-related burden was measured in three primary care clinics in Qatar using the Living with Medicines Questionnaire (LMQ) among adults with diabetes, with or without other comorbidities. Adherence was measured using the Adherence to Refills and Medications Scale (ARMS). Two hundred ninety-three eligible patients participated in the study. Majority of participants reported experiencing minimum (66.6%) to moderate (24.1%) medication-related burden. There was a significant positive correlation between the medication-related burden (measured by the LWQ) and medication adherence (measured by ARMS) (rs (253) = 0.317, p <0.0005). The duration of diabetes diagnosis, adherence score, marital status, employment status, and presence diagnosis of hypertension were significant predictors of medication burden. A considerable proportion of the patients in this study have reported experiencing medication-related burden. Healthcare providers should seek strategies to address this burden especially among patients with risk factors of cardiovascular diseases, non-adherent to their medication therapy, living alone, or non-employed.

Introduction: This study explored the structural relationship between peer relations, exercise participation satisfaction, exercise commitment, and adherence to intention to exercise among Korean sports club participants. The objective was to offer insights that can enhance intentions for continuous exercise participation. Methods: To fulfill this objective, data were gathered using snowball sampling from teenagers at middle schools in Seoul and Gyeonggi, South Korea, who either currently participate in school sports clubs or have participated in the past. A total of 261 responses were analyzed using frequency, technical statistics, and confirmatory factor, reliability, correlation, and structural equation model analyses. Results: Through these analyses, this study found that peer relationships, exercise participation satisfaction, and exercise commitment were significant as both direct and indirect influences on exercise adherence intentions. Discussion: Intervention strategies should focus on fostering the positive emotions that stem from peer relationships.

Carbohydrates such as fructooligosaccharides (FOS) are associated with improved gastrointestinal health and prevention of excess body fat. We evaluated the long-term effects of high amounts of FOS on metabolic parameters, non-alcoholic fatty liver disease (NAFLD) and short-chain fatty acids (SCFA). Sixty C57BL/6 mice received diets for four months: control (C), normolipid rich in fiber (F), normolipid supplemented with FOS (FOS), high fat (HL), high fat with high fiber (HLF) and high fat with FOS (HLFOS). We analyzed: animal weight; body composition; food intake; fasting blood glucose; serum and liver lipid profile; liver and intestinal histologies; malondialdehyde (MDA), hepatic retinol and α-tocopherol; SCFA in the feces. Supplementation with FOS in a high-fat diet promoted less body weight gain and reduced liver and retroperitoneal adipose tissue weights compared to HL and HF. FOS prevented NASH and decreased alanine aminotransferase and serum cholesterol levels in experimental animal models of obesity and metabolic syndrome (MS). There was found statistical differences in the dosages of the three main SCFAs in feces (acetic, isobutyric and isovaleric acids). Long-term supplementation with high doses of FOS was effective in reducing weight, adiposity, NAFLD and serum cholesterol in C57BL mice with obesity and MS induced by a high-fat diet.

(1) Background: Although multiple studies have reported on the therapeutic effects of Atezo+Bev for the treatment of NASH-related liver cancer, few studies have focused on its effect on liver reserve. Here, we aimed to compare the changes in hepatic reserve during the Atezo+Bev treatment of NAFLD/NASH-related HCC and of non-NAFLD/non-NASH-related HCC. (2) Methods: We retrospectively compared the changes in ALBI score in 109 patients with NAFLD/NASH or non-NAFLD/non-NASH during 12 weeks of treatment with Atezo+Bev for advanced HCC between September 2019 and January 2022. PSM was performed, and the OS, PFS, and PPS of the two groups were compared. (3)Results: The ALBI after 12 weeks of Atezo+Bev treatment was significantly worse in the NAFLD/NASH group than in the non-NAFLD/non-NASH group. Analysis of the 24 propensity score-matched pairs of cases with NAFLD/NASH or non-NAFLD non-NASH yielded similar results. The prognoses of the two groups were similar with respect to OS and PFS, but the NAFLD/NASH group had a significantly shorter PPS. The 24 matched pairs had similar OS and PFS, but the PPS of the NAFLD/NASH group was shorter. (4)Conclusion: Atezo+Bev treatment may worsen hepatic reserve, and there-fore life expectancy, in patients with NAFLD/NASH-related liver cancer.

The optimal therapy for patients with non-metastatic biochemically relapsed prostate cancer (BRPC-M0) after local therapy is elusive. Thus, the evaluation of new non-toxic compounds in BRPC-M0 patients is warranted. PectaSol® modified citrus pectin (P-MCP) is a food supplement generally recognized as safe (GRAS) by the Food and Drug Administration (FDA) and is a competitive inhibitor of galectin-3 protein, involved in cancer pathogenesis. P-MCP treatment of BRPC-M0 patients for 6 months led to a 75% prostate-specific antigen doubling time (PSADT) improvement. To determine the longer-term effects of P-MCP we investigated an additional 12 months of treatment (phase II) with oral P-MCP at 4.8 grams X 3/day in patients with no disease progression in the previous 6 months. Of the 46 patients that entered the second phase, 7 patients withdrew consent and continued therapy independently, and 39 received another 12 months of therapy. After a total of 18 months P-MCP treatment, 62% (n=24) had a decreased/stable PSA, 90% (n=35) had improved PSADT, and 85% (n=33) had a durable long-term response, with a decreased/stable PSA, and/or improvement of PSADT, and negative scans. No patient had grade 3/4 toxicity. In conclusion, P-MCP may have long term durable efficacy, and is safe, in BRPC-M0.

Autosselecionar a intensidade do treinamento aeróbico é uma perspectiva que permite aos praticantes desenvolver autonomia (escolha do ritmo), melhorar a aptidão física e alcançar a perda de peso. Comparar o efeito de quatro protocolos de treinamento aeróbico nas respostas cardiometabólicas e psicofisiológicas em homens e mulheres adultos fisicamente inativos. A amostra foi composta por 11 indivíduos com idade entre 56 ± 10 anos e IMC 29,2 ± 2,4 kg/m2 que realizaram quatro diferentes protocolos de treinamento aeróbio em esteira, sendo: 1-indivíduo com intensidade autosselecionada (ISS), 2-indivíduo com intensidade prescrita (IPI) (64-76% da FC máx), grupo 3 pequeno com autosseleção. intensidade selecionada (SGS) e intensidade prescrita em 4 pequenos grupos (SGP) (64-76% da FC máx). Foram analisados ​​frequência cardíaca, lactato, percepção subjetiva de esforço, resposta afetiva, escala de ativação, prazer, intenção de repetir a sessão, velocidade da esteira e distância total do protocolo. A análise estatística utilizou ANOVA com teste post hoc de Tukey (p<0,05). As análises de frequência cardíaca, lactato, percepção subjetiva de esforço, escala de ativação, prazer, velocidade média e distância total não apresentaram diferenças significativas entre os protocolos. A resposta afetiva apresentou menor declínio no protocolo ISS (p<0,05), e a intenção de repetir a sessão de treinamento foi maior no protocolo ISS (p<0,05). Conclusão: Os dados permitem concluir que o protocolo de treino ISS produziu resultados superiores na resposta afetiva e na intenção de repetir a sessão.

Introduction: Type 2 Diabetes mellitus (T2DM) is a common disease burdened with significant morbidity and mortality. Despite the substantial number of new available drug treatments, adherence to therapy and adverse drug reactions (ADRs) are the major constrain in the management of this disease. We evaluated the use, the adherence and the dsaftey of antidiabetic drugs in patients with T2DM. Methods: we performed an observational, retrospective, multicenter study on medical records of outpatients referred to general practitioners. Drug adherence was measured in agreement to the European Society for Patient Adherence, Compliance and Persistence Medication Adherence Reporting Guideline. ADRs were evaluated using the Naranjo probability scale. Collected data were analyzed using the Statistical Package for the Social Sciences. Results: During the study we evaluated 12,170 medical records of 7 general practitioners. The most prescribed drug was metformin alone (28.4%) or with other oral antidiabetics (19.6%) and then insulin (n: 354; men 190, women 164). Enrolled patients were stratified as high (35%), medium (41%) and low (24%) adherence. Logistic regression showed an association between T2DM less than or equal to 5 years and low adherence (P = 0.023). During the study we recorded 26 ADRs that was correlated with sex (women) and insulin treatment. Conclusion: this real-life study shows that patients with T2DM have high adherence probably related dto a low number of ADRs

Diagnosis and treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in women remain insufficient. Fluctuations of reproductive hormones during the premenstrual period, postpartum period and (peri)menopause are neglected, even though they impact ADHD symptoms and as-sociated mood disorders [1]. Therefore, we created a female-specific treatment group for women with ADHD and premenstrual worsening of ADHD and/or mood symptoms. We describe the group programme and underlying rationale, offering a qualitative analysis of the participants’ evaluation. The 7 two-weekly sessions foreground the menstrual cycle and address several ADHD-specific topics in relation to this cyclical pattern: emotional regulation; impulsivity; setting boundaries, and triggers. Concurrently, women track their menstrual cycle and (fluctuating) ADHD and mood symptoms with an adjusted premenstrual calendar. In total, 18 women (25-47yrs) participated in three consecutive groups. We analysed the evaluation of the last group. Participants experienced the group as a safe and welcoming space. Recognition was valued by all. The topics discussed were deemed valuable and the structure suited them well. Completing the premenstrual calendar augmented awareness and recognition of individual cyclical symptoms. Discussing ADHD throughout the lifespan increased self-understanding. Participants took their menstrual cycle more seriously, prioritising self-acceptance and self-care in the luteal phase of the cycle. Exploring a cyclical approach in a group setting seems to be a positive addition to treatment for female ADHD.

Water pollution, intensified by the release of hard-to-degrade pollutants, poses severe threats to ecosystems, human health, and economic development. The existing advanced oxidation processes often involve high operational costs and may result in secondary pollution, highlighting the necessity for innovative and more sustainable solutions. To address these challenges, our study introduces a cost-effective and eco-friendly corona discharge barrier plasma discharger for wastewater treatment. Through the central composite design/response surface methodology, a high decolorization rate of 98% of methylene blue (MB) within 10 minutes was achieved by optimizing parameters such as pH and voltage. Furthermore, the mechanisms of the generation of reactive oxygen species via this device was discussed in detail and the degradation pathways of MB were described. Moreover, this device is also very energy-efficient, with a low energy density and electrical energy per order of 0.15 watt/mL and 5.79 kWh/m³/order, respectively. In conclusion, the plasma discharger developed in this study provides a cost-effective and environmentally sustainable solution for dye wastewater treatment. This research contributes significantly to the advancement of sustainable dye wastewater management practices, offering an innovative method that meets both environmental and economic objectives.

Lung cancer is the leading cause of cancer death worldwide, with non-small cell lung cancer (NSCLC) making up 80% of cases. Some genetic factors leading to NSCLC development include genetic mutations and PD-L1 expression. PD-L1 proteins are targeted in an NSCLC treatment called targeted gene therapy. However, this treatment is effective in a low percentage of patients. This study aimed to create machine learning models to use features like the number of mutations and the level of PD-L1 proteins in cancer cells, along with others, to predict whether a patient will receive clinical benefit from gene therapy treatment. This was done by downloading and merging datasets from cbioportal.org to create a sample size for the model. Features with high correlations to clinical benefit were identified. Three machine-learning models were created using these features to predict clinical benefits in patients, and each model’s accuracy was evaluated. All three models were accurate between 55-85%, with two of the models averaging an accuracy around 75%. Doctors can use these models to more accurately predict whether gene therapy treatment is likely to work in a patient before prescribing it to them.

Introduction: The transcranial direct current stimulation (tDCS) is a promising technique for brain modulation after cerebrovascular accident (CVA). This treatment modality has been previously studied in the recovery of patients. The aim of this review is to analyze the evidence in the ap-plication of tDCS in the recovery of gait disturbance in stroke patients. Methods: This review was conducted according to the recommendations of the PRISMA statement. Three different elec-tronic databases were searched for relevant results: PubMed, Scopus, and Cochrane. We included reviews and meta-analyses that only considered randomized controlled trials (RCTs) that inves-tigated the effects of transcranial direct electrical stimulation, in combination or not with other physiotherapy treatment, on gait recovery. Results: Thirteen studies with a total of 195 RCTs were included. Data on population, outcome measures, protocols and outcomes were extracted. The Amstar-2 scale and the GRADE system of certainty of evidence were used. Only one study re-ceived high certainty of evidence, 5 received low certainty of evidence and 7 received critically low certainty of evidence. Conclusions: Although the tDCS produces positive changes in gait recovery in spatio-temporal parameters, mobility, endurance, strength and motor function, there is insuf-ficient evidence to recommend this treatment.

Abstract: Female pelvic floor dysfunction (FPFD) is a series of conditions caused by the displacement or dysfunction of the patient's pelvic organs due to defects, injuries, and deterioration of the pelvic floor supportive structures, with stress urinary incontinence and pelvic organ prolapse being the most common. The mechanism of pelvic floor dysfunction is complex and not yet fully understood, and is often related to one or more functional abnormalities of muscles, connective tissues, fascia, nerves and blood vessels. Specialized clinicians are often unable to cover the comprehensive medical professional information of various specialties such as gynecology and obstetrics, urology, anus and intestines, imaging, etc., and the systematic and comprehensive diagnosis and treatment of the disease will be limited. The application of artificial intelligence concepts in the medical field not only improves the diagnostic efficiency of physicians, but also provides reference and basis for the development of comprehensive treatment programs. This article follows and draws on the diagnosis and treatment process of pelvic floor dysfunction recommended in various guidelines, incorporates physical therapy techniques into the conventional non-surgical treatment of pelvic floor dysfunction, provides guidance for the diagnosis and treatment of pelvic floor dysfunction, and briefly introduces the clinical application and value of pelvic floor intelligent diagnosis and treatment in pelvic floor dysfunction.

Objective tools to track medication adherence are lacking. A tool to monitor pill intake that can be implemented in mHealth apps without the need for additional devices was developed. We propose a pill intake detection tool that uses digital image processing to analyze images of a blister to detect the presence of pills. The tool uses the circular Hough transform as a feature extraction technique and is therefore primarily useful for the detection of pills with a round shape. This pill detection tool is composed of two steps. First, the registration of a full blister and storing of reference values in a local database. Second, the detection and classification of taken and remaining pills in similar blisters, to determine the actual number of untaken pills. In the registration of round pills in full blisters, 100% of pills in gray blisters or blisters with a transparent cover were successfully detected. In counting of untaken pills in partially opened blisters, 95.2% of remaining and 95.1% of taken pills were detected in gray blisters, while 88.2% of remaining and 80.8% of taken pills were detected in blisters with a transparent cover. The proposed tool provides promising results for the detection of round pills. However, the classification of taken and remaining pills need to be further improved, in particular for the detection of pills with non-oval shapes.

Objectives: To determine the prevalence of controlled systemic hypertension and its associated risk factors among the hypertensive patients who attended the clinic at Mbeya Zonal Referral Hospital in Tanzania. Methods: A descriptive cross-sectional quantitative study was used determine the prevalence of co to 252 hypertensive patients were recruited during clinic visit from September to November 2020 and participant was randomly selected interviews using structured self-administered questionnaires. Data was analyzed using chi square test to find the risk factors associated with controlled hypertension. Results: Among 252 participants, 94(39.7%) individuals with controlled hypertension giving the prevalence of controlled hypertension. The proportion of females with controlled hypertension was slightly higher than male (49 females to 45 males). The prevalence of uncontrolled hypertension was 152(60.3%) participants. The prevalence of controlled hypertension was higher among patients who have regular clinic visit (p< .05) and have daily adherence to their anti-hypertensive medication. A similar trend was observed among participants without financial challenges to attend clinic, short duration of illness, higher level of education and there was no association between age, sex, marital status, smoking, alcohol consumption, having health insurance and having chronic illness. Conclusion: Prevalence of controlled hypertension is higher among patients who have regular clinic visit and have daily adherence to their anti-hypertensive medication. Also, it is higher among participants without financial challenges to attend clinic so they can have regular clinic visit and checkup. Reinforcement on regular drug intake and clinic visit, good nutrition and reduced salt intake and modifying lifestyles of patient with hypertension is important.

The assessment of an organization/product's environmental footprint is based on the protocols developed by the Joint Research Centre of the European Union, which take into account 16 impact categories. Among the categories covered are toxicity to freshwater ecosystems and to humans. Standard protocols use only chemical parameters as input data, preventing the true impact of entire complex mixtures, such as emissions discharged into the environment, from being determined. Biological assays allow us to bridge this gap: in the current study, assays were used to determine baseline toxicity towards aquatic organisms (green algae, luminescent bacteria, and crustaceans) as well as specific toxicity (mutagenicity and carcinogenicity). Expected impacts were compared using two approaches (standard and bioassay-centered results obtained are not always in line and, in general, the traditional method underestimates impacts). This demonstrates the importance of these assays and suggests that they be used in LCA (Life Cycle Assessment) protocols as well.

Recent research has implicated the gut microbiota in the development of lymphoma. Dysbiosis of the gut microbial community can disrupt the production of gut microbial metabolites, thereby impacting host physiology and potentially contributing to lymphoma. Dysbiosis-driven release of gut microbial metabolites such as lipopolysaccharides can promote chronic inflammation, potentially elevating the risk of lymphoma. In contrast, gut microbial metabolites, such as short-chain fatty acids, have shown promise in preclinical studies by promoting regulatory T-cell function, suppressing inflammation, and preventing lymphoma. Another metabolite, urolithin A, exhibited immunomodulatory and antiproliferative properties against lymphoma cell lines in vitro. While research on the role of gut microbial metabolites in lymphoma is limited, this article emphasizes the need to comprehend their significance, including therapeutic applications, molecular mechanisms of action, and interactions with standard chemotherapies. The article also suggests promising directions for future research in this emerging lymphoma and gut microbiome investigation field.

The advent of immunotherapy has revolutionized the treatment of advanced non-small cell lung cancer (NSCLC), improving the prognosis of this disease and becoming a key part of the treatment, especially in the population without an oncogenic driver mutation. Two different groups of immune checkpoint inhibitors (ICIs) are used in lung cancer: Anti- Cytotoxic T-lymphocyte antigen-4 (Anti-CTLA 4) and Anti- T-cell receptor programmed cell death-1 or its ligand (Anti-PD-1 and Anti PD-L1). Here in, we review an uptodate on the use of immunotherapy for advanced NSCLC.

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

Biological systems are highly regulated. They are also highly resistant to sudden perturbations enabling them to maintain the dynamic equilibrium essential for sustenance of life. This robustness is conferred by regulatory mechanisms that influence the activity of enzymes/proteins within their cellular context, to adapt to changing environmental conditions. However, the initial rules governing the study of enzyme kinetics were tested and implemented for mostly cytosolic enzyme systems that were easy to isolate and/or recombinantly express. Moreover, these enzymes lacked complex regulatory modalities. Now, with academic labs and pharmaceutical companies turning their attention to more complex systems (for instance, multi-protein complexes, oligomeric assemblies, membrane proteins and post-translationally modified proteins), the initial axioms defined by Michaelis-Menten (MM) kinetics are rendered inadequate and the development of a new kind of kinetic analysis to study these systems is required. The current review strives to present an overview of enzyme kinetic mechanisms that are atypical and, oftentimes, do not conform to the classical MM kinetics. Further, it presents initial ideas on the design and analysis of experiments in early drug-discovery for such systems, to enable effective screening and characterisation of small-molecule inhibitors with desirable physiological outcomes.

Celiac disease (CD) is a genetically conditioned autoimmune process that appears in susceptible people. It can affect people of any age, and slightly predominates in females. It has a fairly homogenous global distribution, with an average prevalence of 1-2%, the frequency having increased in recent decades. The only effective treatment is a strict and permanent gluten-free diet (GFD), although the level of compliance with it is poor, at about 50% of cases. To monitor the effectiveness of the GFD, several procedures involving various approaches are employed: a) periodic interviews by nutritionists; b) clinical follow-up; c) serological controls of specific antibodies; d) endoscopies with collection of duodenal biopsies; e) structured questionnaires; f) determination of gluten peptides derived from gluten in feces and/or urine. All of these procedures are useful when applied, alone or in combination, depending on the cases. Some patients will only need to consult to their doctors, while others will require a multidisciplinary approach to assess their compliance with the GFD. In children, normalization of duodenal mucosa was achieved in 95% of cases within 2 years, while it is more delayed in adults, whose mucosa take longer to heal completely.

Non-Small Cell Lung Cancer (NSCLC) is the most common pulmonary malignancy, most frequently diagnosed at an advanced stage (III/IV). Patients in the Locally-Advanced Stage Subgroup (IIIA) are relatively few, yet compose of heterogenic phenotypes posing a diagnostic and treating challenge, leading to lack of clinical guidelines regarding the optimal standard of care. Several approaches exist, with a general agreement that a combined oncological and surgical modality approach is required. In this current retrospective descriptive study, operable Stage IIIA NSCLC patients who underwent surgery between 2013-2020 were evaluated on several aspects, including initial diagnosis, neoadjuvant regimens, outcomes of surgical intervention, overall survival at 2-years and 5-years following treatment. A total of 35 patients had neoadjuvant oncological treatment (mostly chemoradiation therapy) prior to surgery, out of which 28 patients were diagnosed with Stage IIIA NSCLC. In post-operative assessment of pathological staging, downstaging was reported in 20 patients, of which 7 (25%) cases were defined as complete pathological response. The 2-years overall survival rate was 65% and the 5-years overall survival rate was 60%. The main pattern of disease recurrence was distant metastasis.

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

In this paper, existence and stability results of non-local integro-differential equation with Hilfer derivative of order ω∈(1,2) have been investigated. In this derivative is applied in RLC circuit equation of various fractional order. To proposed problem the existence solutions are derived using Schaefer’s fixed point theorem and the Banach contraction principle is using for uniqueness results. To demonstrate the effectiveness and applicability of our theoretical conclusions and two-step Lagrange polynomial interpolation were used to solve four numerical results.

Intradermal injection of botulinum neurotoxin is a frequently performed procedure in aesthetic dermatology to improve facial skin tone, texture, fine wrinkles, and enlarged pores. In practice, botulinum neurotoxin type A is also used to reduce skin oiliness of the face. There is increasing evidence that acetylcholine plays specific roles in sebum production, suggesting that botulinum neurotoxin type A may reduce sebum production by interfering with cholinergic transmission between sebaceous glands and autonomic nerve terminals. Botulinum neurotoxins can also inhibit several pathogenetic components of acne development, suggesting that botulinum neurotoxins can be used as a safe and effective treatment modality for acne and other skin disorders related to the overactivity of sebaceous glands. This review aims to explore the current evidence behind the treatment of oily skin and acne with botulinum neurotoxin type A.

The rapid advancements in gene therapy have opened up new possibilities for the treatment of genetic disorders, including Duchenne muscular dystrophy, Thalassemia, cystic fibrosis, Hemophilia, and Familial hypercholesterolemia. The utilization of the clustered regularly interspaced short palindromic repeats (CRISPR) - CRISPR-associated protein (Cas) system has revolutionized the field of gene therapy by enabling precise targeting of genes. In recent years, CRISPR/Cas9 has demonstrated remarkable efficacy in treating cancer and genetic diseases. However, the susceptibility of nucleic acid drugs to degradation by nucleic acid endonucleases, necessitates the development of functional vectors capable of protecting the nucleic acids from enzymatic degradation, while ensuring safety and effectiveness. This review aims to explore the biomedical potential of non-viral vector-explore CRISPR/Cas9 systems for the treatment of genetic diseases. Furthermore, it provides a comprehensive overview of recent research advances in viral and non-viral vector-based gene therapy for genetic disorders, including insights from preclinical and clinical studies. Additionally, the review analyzes the current limitations of these delivery systems and proposes avenues for the development of novel nano-delivery platforms.

Near-fault ground motions can cause severe damage to civil structures, including bridges. Safety assessment of these structures for near fault ground motion is usually performed through Non-Linear Dynamic Analyses, while faster methods are often used. IMPAb (Incremental Modal Pushover Analysis for Bridges) permits to investigate the seismic response of a bridge by considering the effects of higher modes, which are often relevant for bridges. In this work, IMPAb is applied to a bridge case study considering near-fault pulse-like ground motion records. The records were analyzed and selected from the European Strong Motion Database and the pulse parameters were evaluated. In the paper results from standard pushover procedures and IMPAb are compared with nonlinear Response-History Analysis (NRHA), considering also the vertical component of the motion, as benchmark solutions and incremental dynamic analysis (IDA). Results from the case study demonstrate that the vertical seismic action has a minor influence on the structural response of the bridge. Therefore IMPAb, which can be applied considering vertical motion, remains very effective conserving the original formulation of the procedure, and can be considered a well performing procedure also for near-fault events.

In the last century, statistical process control has been considered a successful methodology for monitoring the variability and stability of a process over time. The analysis of variability using functional data analysis has become widespread during the early years of the 21st century. The present study proposes the implementation of a hybrid methodology called functional process control based on the functional data analysis methodology and combines its advantages with those of statistical process control, in order to provide a tool for detecting functional deviations. The phases are: (1) stabilization of processes through the identification and elimination of special causes of functional variability; (2) improvement of the process to be controlled by minimizing the common causes of functional variability; and (3) monitoring of the processes to ensure the maintenance or addition of further improvements.

Cellulose nanocrystals (CNCs) are cellulose-derived nanomaterials that can be easily obtained, e.g., from vegetable wastes produced by circular economies. They show promising antimicrobial activity and the absence of side effects and toxicity. This study investigated the ability of CNCs to reduce microbial adherence and biofilm formation using in vitro microbiological models reproducing the oral environment. Microbial adherence by microbial strains of oral interest, Streptococcus mutans and Candida albicans was evaluated on the surfaces of salivary pellicle-coated enamel disks in the presence of different aqueous solutions of CNCs. The antibiofilm activity of the same CNC solutions was tested against S. mutans and an oral microcosm model based on mixed plaque inoculum using a continuous-flow bioreactor. Results showed an excellent anti-adherent activity of the CNCs against the tested strains from the lowest concentration tested (0.032 wt.%). Such activity was significantly higher against S. mutans than C. albicans, suggesting a selective anti-adherent activity against pathogenic strains. At the same time, there was a minimal albeit significant antibiofilm activity (at least 0.5 and 4 wt.% CNC solution for S. mutans and oral microcosm, respectively). This makes CNCs particularly interesting as anticaries agents, encouraging their use in the oral field.

Titanium dioxide (TiO2) thin films have been widely used in transparent optoelectronic devices owing to their excellent optical properties also is used in photocatalysis, cosmetics, and many other biomedical applications. However, a lack of studies was published on microstructure and adherence comparison of the TiO2 deposited on both AISI substrates. In this work, TiO2 thin films were deposited onto AISI 304 and AISI 316L stainless steel (SS) substrates via atomic layer deposition. Its heterostructure, morphology, and adhesion were compared in both substrates looking for synergistic and multifunctional properties. Raman spectroscopy mapping and X-ray diffraction using the Rietveld refinement method showed that the films are composed of anatase and rutile phases in different percentages. Scratching tests were used to analyze the film adher-ence and friction between a diamond tip and TiO2 film, showing well adhered in both substrates.

Although adult spontaneous (non-diabetic) hypoglycaemia is rare, its recognition is important for the preventative or curative treatment of the underlying cause. Establishing Whipple’s triad; low blood glucose, neuroglycopaenia and resolution of neuroglycopaenia on increasing blood glucose levels to normal or above, is essential to verify hypoglycaemia. Awareness that hypoglycaemia may occur in severely ill patients is important for its prevention. Further investigation in such cases is unnecessary unless another cause of hypoglycaemia is suspected. Patients are often asymptomatic and normoglycaemic at review. History of medication, self-medication, access to hypoglycaemic drugs, alcohol and comorbidity may provide aetiological clues. The investigation involves obtaining blood samples during symptoms for laboratory glucose measurement or provoking fasting or postprandial hypoglycaemia as directed by symptoms. If confirmed, insulin, c-peptide, proinsulin, beta-hydroxybutyrate are analysed in hypoglycaemic samples. These will classify hypoglycaemia due to non-ketotic hyperinsulinaemia, non-ketotic hypoinsulinaemia and ketotic hypoinsulinaemia and direct investigations to identify the underlying cause. There are, however, many pitfalls, which may mislabel healthy individuals as “hypoglycaemic” or misdiagnose treatable or preventable causes of spontaneous hypoglycaemia. Clinical acumen and appropriate investigations will mostly identify hypoglycaemia and its cause.

Addressing non-unions involves stabilizing the affected area through osteosynthesis and improving bone biology using bone grafts. However, there is no consensus on the optimal treatment method. This study aims to compare outcomes of non-union revision using conventional treatment methods (metal hardware ± graft) versus osteosynthesis with the human, allogeneic cortical bone screw (Shark Screw®). Thirty-four patients underwent conventional treatment, while 28 cases received Shark Screws®. Patient demographics, bone healing, time to bone healing, and complications were assessed. Results revealed a healing rate of 96.4% for the Shark Screw® group, compared to 82.3% for the conventionally treated group. The Shark Screw® group exhibited a tendency for faster bone healing (9.4±3.2 vs. 12.9±8.5 weeks, p=0.05061). Hardware irritations led to six metal removals in the conventional group versus two in the Shark Screw® group. The Shark Screw® emerges as a promising option for personalized non-union treatment in the foot, ankle, and select lower leg cases, facilitating effective osteosynthesis and grafting within a single construct, promoting high union rates, low complications, and a rapid healing process.

This paper discusses a means of making an extremely bright path entangled source. An initial laser source is preferred but any source of light: LED, sub-critical laser, coherent or thermal can be used. The light is dimmed by a beam expander until the relative number of |1> or |2> photons increases compared to higher photon states. The expanded beam is then passed through a 1:1 beamsplitter to generate path entanglement on the |1> and |2> photons. A further stage of “purification” can remove the non-entangled higher states by passing the output beams from the beamsplitter through one another, such that the correlated entangled photon electrical fields cancel in some region. In the said region, the uncorrelated non-entangled fields can be Faraday rotated and then absorbed by a polariser. The entangled photons pass through the region without rotation and attenuation. The output from the device then has copious quantities of 1 and 2 photon path entangled suitable for use in telecommunications engineering, secure transmission of data and quantum metrology. The wide beams can be beam-contracted to a thin bright beam and will keep the path entanglement of individual photons, as photons are bosons and so don’t interact, furthermore, all operations are unitary and linear, as by Maxwell’s equations.

Metformin is an oral antidiabetic agent with antimicrobial properties, excreted in an active and unmetabolized form. Like some non-antibiotic drugs, subinhibitory concentrations of metformin may contribute to the expression of microbial resistance in wild-type strains. This work aimed to evaluate the biofilm formation of Pseudomonas aeruginosa TGC04 exposed to 100 and 200 µg/mL of metformin, varying the Chemical Oxygen Demand (COD) and flow regime. Biofilms were quantified after 2 and 24 hours, observing reductions and increases in biofilm growth around 13 and 64%, respectively. The greatest biofilm growth occurred in cells exposed to 200 µg/mL of metformin. Both the flow regime and COD concentration were important for the development of the biofilm, whose cells were mostly weakly to moderately adhered. The study provides evidence that in polluted aquatic systems with turbulent regimes, the inhibitory concentration of metformin promoted the least disturbances to the biofilm.

Gradual disability worsening in Multiple Sclerosis (MS) is indicative of confirmed progression that mostly involves progression independent of relapse activity (PIRA) and is associated with neurodegeneration. Insights from pathology reveal grey matter involvement (neocortex, hippocampus, spinal cord, and deep grey matter structures) and microglia activation in early stages of MS. Cortical lesions result in thinning and atrophy and are considered accurate predictors of disability progression and cognitive decline.Neuroimaging biomarkers, such as high-resolution 7T MR images and TSPO-PET, have been examined for the detection of cortical pathology linked to cognitive deficits and thus progression, but are limited in clinical practice due to availability, time constraints, and cost.Electroencephalography (EEG) emerges as a non-invasive, cost-effective tool that reflects cortical activity in MS. Its potential in monitoring cognitive impairment is explored by focusing on nonlinear EEG analysis. The MuST PREDICT^TM project aims to extract linear and nonlinear EEG features, investigating their role in predicting disease progression and optimizing treatment. The study employs retrospective, cross-sectional, and prospective designs, utilizing EEGs from various MS forms, cognitive assessments, serum/cerebrospinal fluid biomarkers and neuroimaging. The methodology involves time-based and spectral feature extraction, employing artificial intelligence classifiers and brain criticality-based approaches.The conceptual framework of an innovative modality is herein presented, that would EEG for early MS progression detection. Standardization of the methodology could lead to the creation of a digital tool for better prognostication and treatment strategy optimization.

Entropy generation, formulated by combining the first and second laws of thermodynamics with an appropriate thermodynamic potential, emerges as the difference between a phenomenological entropy function and a reversible entropy function. The phenomenological entropy function is evaluated over an irreversible path through thermodynamic state space via real time measurements of thermodynamic states. The reversible entropy function is calculated along an ideal reversible path through the same state space. Entropy generation models for various classes of systems—thermal, externally loaded, internally reactive, open and closed––are developed via selection of suitable thermodynamic potentials. Here we simplify thermodynamic principles to specify convenient and consistently accurate system governing equations and characterization models. The formulations introduce a new and universal Phenomenological Entropy Generation (PEG) theorem. The systems and methods presented––and demonstrated on grease degradation, battery charging and discharging, metal fatigue and pump flow––can be used for design, analysis, and support of diagnostic monitoring and optimization.

Advances in next-generation sequencing have facilitated the discovery of a multitude of long non-coding RNAs (lncRNAs) with pleiotropic functions in cellular processes, disease and viral pathogenesis. It came as no surprise when viruses were also revealed to transcribe their own lncRNAs. Among them, gammaherpesviruses, one of the three subfamilies of the Herpesviridae, code their largest number. These structurally and functionally intricate non-coding (nc) transcripts modulate cellular and viral gene expression to maintain viral latency or prompt lytic reactivation. The lncRNAs allow the virus to escape cytosolic surveillance, sequester and re-localize essential cellular factors and modulate the cell cycle and proliferation. Some viral lncRNAs act as “messenger molecules”, transferring information about viral infection to neighboring cells. This broad range of lncRNA functions is achieved through lncRNA structure-mediated interactions with effector molecules of viral and host origin, including other RNAs, proteins and DNAs. In this review, we discuss examples of gammaherpesvirus-encoded lncRNAs, emphasize their unique structural attributes, and link them to viral life cycle, pathogenesis and disease progression. We will address their potential as novel targets for drug discovery and propose future directions to explore lncRNA structure and function relationship.

The Gilles de la Tourette syndrome (GTS) and Non-Coeliac Gluten Sensitivity (NCGS) may be associated. We analyse the efficacy of a gluten-free diet (GFD) in 29 patients with GTS (23 children; 6 adults) in a prospective pilot study. All of them followed a GFD for one year. The YGTSS, Y-BOCS/CY-BOCS and GTS-QOL questionnaires were compared before and after the GFD. 74% of children and 50% of adults were males, not significant (NS). At the beginning of the study, 69% of children and 100% of adults had associated OCD (NS). At baseline, the YGTSS scores were 55.0 ± 17.5 (children) and 55.8 ± 19.8 (adults) (NS), the Y-BOCS/CY-BOCS scores were 15.3 (SD = 12.3) (children) and 26.8 (9.2) (adults) (p = 0.043), and the GTS-QOL scores were 42.8 ± 18.5 (children) and 64 ± 7.9 (adults) (p = 0.000). NCGS was frequent in both groups, with headaches reported by 47.0% of children and 83.6% of adults (p = 0.001). After one year on a GFD there was a marked reduction in measures of tics (YGTSS) (p = 0.001), and the intensity and frequency of OCD (Y-BOCS/CY-BOCS) (p = 0.001), along with improved QOL (p = 0.001) in children and adults. In conclusion, a GFD maintained for one year in GTS patients led to a marked reduction in tics and OCD both in children and adults.

This study aimed to develop extended–release tablets containing 25 mg IMM−H014, an original drug formulated by a direct powder pressing method based on pharmaceutical–grade hydrophilic matrix polymers, such as hydroxypropyl methylcellulose, to establish an in vitro−in vivo corre-lation (IVIVC) to predict bioavailability. The tablets’ mechanical properties and in vitro and in vivo performance were studied. The formulation was optimized using a single factor experiment and the reproducibility was confirmed. The in vitro dissolution profiles of the tablet were de-termined in five dissolution media, in which the drug released from the hydrophilic tablets fol-lowed Ritger–Peppas model kinetics in 0.01 N HCl medium for the first 2 h, and in phosphate buffer saline medium (pH 7.5) for further 24 h. Accelerated stability studies (40°C, 75% relative humidity) proved that the optimal formulation was stable for 6 months. The in vivo pharmaco-kinetics study in beagle dogs showed that compared to the IMM−H014 immediate release prep-aration, the maximum plasma concentration of the extended release (ER) preparation was sig-nificantly decreased, while the maximum time to peak and mean residence time were significantly prolonged. The relative bioavailability was 97.9% based on an area under curve, indicating that the optimal formulation has an obvious ER profile. And a good IVIVC was established, which could be used to predict in vivo pharmacokinetics from the formulation composition.

Background/Aim: Baricitinib (BAR) is the first oral selective Janus kinase inhibitor approved in Europe for rheumatoid arthritis (RA). Real-world data are still needed to clarify its long-term benefit/risk profile. This study aimed to evaluate the effectiveness, persistence, adherence, and safety of BAR in a real-world setting. Methods: An ambispective study was conducted between October 2017 and December 2021 in RA patients starting BAR. Effectiveness was evaluated by change from baseline in the Disease Activity Score using 28-joint counts-C reactive protein (DAS28CRP), and achievement of low disease activity/remission. Drug persistence was evaluated by Kaplan-Meier analysis. Adherence was estimated by medication possession ratio (MPR) and the 5-item Compliance Questionnaire for Rheumatology. Safety was assessed by global incidence proportion and adjusted incidence rates of adverse events. Results: 61/64 recruited patients were finally analyzed, 83.6% female, 78.7% seropositive, mean age of 58.1 (15.4) years, and disease duration of 13.9 (8.3) years. 32.8% were naïve to biologics and 16.4% received BAR on monotherapy. After a median exposure to BAR of 12.4 (6.6-31.2) months (range 3.1-51.4), a significant change in DAS28CRP was observed (difference -1.2, p=0.000). A total of 70.5% and 60.7% patients achieved low disease activity or remission, respectively and 50.8% (31/61) patients remained on BAR during follow-up with a median persistence of 31.2 (9.3-53.1) months. The average MPR was 0.96 (0.08) and all patients were “good adherents” by questionnaire. 21.3% patients discontinued baricitinib due to toxicity. Conclusion: In our real-world practice, BAR demonstrated effectiveness, large persistence, high adherence to treatment and acceptable safety profile.

The regenerated magnesia-calcium brick samples that had added 0, 1.5, 3.0 wt.% aluminium oxide (Al2O3) were prepared by using spent magnesia-calcium bricks, fused magnesia and Al2O3 powder additive as the main raw materials. The phases, microstructures, room temperature and hot flexural strength, resistance to cement clinker corrosion and strength of coating adherence were investigated respectively. It indicated that the addition of Al2O3 increased mainly resulting in the content of tetracalcium aluminoferrite (C4AF) and tricalcium aluminate (C3A) increased in the regenerate samples. The bulk density, the room temperature flexural strength and the strength of coating adherence all increased, while the hot flexural strength and corrosion resistance both deteriorated along with the increase of Al2O3 addition. It was because that on the one hand the low melting point phases of C4AF and C3A improved the sinterability of the regenerated samples during the burning stage, on the other hand they melted or existed in liquid phase during the experimental temperature (1573 K and 1823 K) which degraded hot flexural strength and corrosion resistance, and enhanced the strength of coating adherence as the wettability of the liquid phase. The content of Al2O3 in the regenerated magnesia-calcium brick should not be higher than 1.1 wt.%, considering its room and high-temperature performances for cement rotary kiln.

EGFR tyrosine kinase inhibitors (TKIs) are the preferred initial treatment for non-small cell lung cancer (NSCLC) patients harboring EGFR mutations. However, remission is transient, and no further effective treatment options are available for EGFR-TKI-advanced EGFR-mutant NSCLCs. Immunotherapy with immune checkpoint inhibitors (ICIs) induces sustained cancer remission in a subset of NSCLCs. However, ICI therapy exhibits limited activity in most EGFR-mutant NSCLCs. Mechanistically, the strong oncogenic EGFR signaling in EGFR-mutant NSCLCs contributes to the non-inflamed tumor immune microenvironment (TIME), characterized by a limited number of CD8+ T cell infiltration, a high number of regulatory CD4+ T cells and a high number of inactivated infiltrated T cells. Besides, EGFR-mutant NSCLC patients are generally non-smokers with low levels of PD-L1 expression and tumor mutation burden. However, current understanding only partially explains why a small population of EGFR-mutant NSCLCs durably respond to ICI therapy, resulting in many researchers actively working in this field. This review reviews the hope seen from pre-clinical studies and clinical trials which may be adopted to improve the outcome of ICI therapy in EGFR-mutant NSCLCs. Besides, the underlying mechanisms leading to the inferior clinical outcome of ICI therapy in EGFR-mutant NSCLCs are discussed.

With improved measurement and modelling technology, variability has emerged as an essential feature in non-equilibrium processes. While traditionally, mean values and variance have been heavily used, they are not appropriate in describing extreme events where a significant deviation from mean values often occurs. Furthermore, stationary Probability Density Functions (PDFs) miss crucial information about the dynamics associated with variability. It is thus critical to go beyond a traditional approach and deal with time-dependent PDFs. Here, we consider atmospheric data from the Whole Atmosphere Community Climate Model (WACCM) and calculate time-dependent PDFs and the information length from these PDFs, which is the total number of statistically different states that a system passes through in time. Time-dependent PDFs are shown to be non-Gaussian in general, and the information length calculated from these PDFs shed us a new perspective of understanding variabilities, correlation among different variables and regions. Specifically, we calculate time-dependent PDFs and information length and show that the information length tends to increase with the altitude albeit in a complex form. This tendency is more robust for flows/shears than temperature. Also, much similarity among flows and shears in the information length is found in comparison with the temperature. This means a stronger correlation among flows/shears because of a strong coupling through gravity waves in this particular WACCM model. We also find the increase of the information length with the latitude and interesting hemispheric asymmetry for flows/shears/temperature, a stronger anti-correlation (correlation) between flows/shears and temperature at a higher (low) latitude. These results also suggest the importance of high latitude/altitude in the information budge in the Earth's atmosphere, the spatial gradient of the information as a useful proxy for the transport of physical quantities.

In this paper, a non-destructive test to diagnose wear of blade´s compressor of a gas turbine is reported. Gas turbine was operating in Campeche City, Mexico, in a very aggressive environment, where the entry of solid particles is unavoidable. The objective was to reduce cost of maintenance in this equipment. Analysis on a blade of gas turbine was performed, which was in operation on an offshore platform. Compressor blade was exposed to a severe damage by the impact of particles and environmental pollutants such as salts, sands and sulphurs. In first stage of this analysis, a visual inspection with a borescope was performed, which has the ability to illuminate dark internal areas, with a bright light for visual examination and/or make a photographic reproduction in semi-annual maintenance cycles. Images analysis was used to determine the typical failure modes. In a second stage, a tribological characterization was carried out. Chemical composition of the material of blades was obtained. Scanning electron microscopy (SEM) was used to measure roughness and evaluate degradation of surfaces of blades after 30,000 service hours. The points, where peak stresses were calculated, correspond to those places in witch corrosion and some irregular scratches similar to plowing action, was observed. These are the points in which failures take place. Results showed wear modes were originated by a severe stinging action. Also, large craters, similar to those observed in solid particle erosion, were developed by at normal impact. In the same way it could be found some localized areas with a witch corrosion and irregular scratches similar to plowing action, was observed. These are the points in which failures take place.

Through the use of a simplified model of consciousness this paper illustrates the symptoms of schizophrenia linked to neocortical structures and functions. It makes the case that the bewildering and varied presentation of symptoms in schizophrenia can be analyzed and explained using such models. The model is used to illustrate the central thesis of the paper, that schizophrenia is a disorder of neurogenesis which leads to progressive neurochemical, functional and neurophysiological changes that create the characteristic behaviors of the disease.

Research into the causes of neurotoxicity in Alzheimer’s Dementia (AD) has focused on neurofibrillary tangles and beta amyloid (Aβ) plaques. This paper proposes the heterodox theory that these hallmarks of AD are the visible effects, not direct causes of neuronal necrosis. Rather AD results from a combination of age-induced, disproportional decline in physiological support for aerobic metabolism, and dysregulation of the sleep cycle processes. The hypothesis is that the decimation of neurons in AD results from a combination of neurotoxicity and increased apoptosis caused by: 1. direct damage from toxic waste products of anaerobic glycolysis due to a progressive decline in the capacity of neurons to perform oxidative phosphorylation (OXPHOS) and an increased reliance on anaerobic glycolysis to meet metabolic needs; 2. impaired cellular repair and effluent release due to dysregulation of non-rapid eye movement (NREM) sleep allowing damage to cell membranes and synaptic junctions to accumulate inducing a chronic inflammatory response; 3. indirect damage from products produced by inflammatory reaction to toxic metabolites; 4. neuronal apoptosis from the AβPP-mediated pathway due to the age-induced decline of growth hormone (GH), GH-releasing hormone (GHRH) and insulin-like growth factor (IGF).

Anticancer regimens for Hodgkin lymphoma (HL) patients include highly genotoxic drugs that have been very successful in killing tumor cells and providing a 90% disease-free survival at five years. However, these treatments do not have a specific cell target, damaging both cancerous and normal cells. Thus, HL survivors have a high risk of developing new primary cancers, both hematologic and solid tumors, that have been related to treatment. Several studies have shown that after-treatment, HL patients and survivors present persistent chromosomal instability, including non-clonal chromosomal aberrations. The frequency and type of chromosomal abnormalities appear to depend on the type of therapy and the cell type examined. For example, MOPP chemotherapy affects hematopoietic and germ stem cells leading to long-term genotoxic effects and azoospermia, while ABVD chemotherapy affects transiently sperm cells, with most of the patients showing recovery of spermatogenesis. Both regimens have long-term effects in somatic cells, presenting non-clonal chromosomal aberrations and genomic chaos in a fraction of non-cancerous cells. This is a source of karyotypic heterogeneity that could eventually generate a more stable population acquiring clonal chromosomal aberrations and leading towards the development of a new cancer.

Non-timber forest Products (NTFPs) are a broad category of natural resources harvested from forests that do not involve cutting down trees for their wood or timber. NTFPs play a vital role in the livelihoods and economies of many rural communities, particularly in forest-dependent regions. Despite the benefits obtained from NTFPS, little is known about its potential to alleviate poverty in the local communities. The objective of this review is to comprehensively assess the potential of NTFP's contribution to poverty reduction within forest fringe communities. The study employed the systematic review method to delve into the multifaceted relationship between NTFPs and poverty alleviation. We followed the preferred reporting items for systematic reviews and meta-analyses protocol (PRISM-P). In all, 58 research articles were reviewed. The results indicated that NTFPs hold significant promise as a tool for poverty alleviation. Globally, NTFPs have the potential to alleviate poverty and increase household incomes between 19% and 78% within forest fringe rural communities. In addition, the review indicated that countries in Africa and Asia depend highly on NTFPs and provide substantial amounts of income to the locals. However, the potential for NTFPs to reduce poverty is not uniform. It is highly contingent upon local ecological conditions, market accessibility, community involvement, and supporting policies and interventions. In conclusion, this systematic review demonstrates that NTFPs have a substantial role in poverty alleviation. This study underscores the need for continued research and targeted development initiatives to unlock the vast potential of NTFPs in addressing poverty challenges.

This review describes the subjective experience of visual aura in migraine, outlines theoretical models of this phenomenon, and explores how these may be linked to neurochemical, electrophysiological and psychophysical differences in sensory processing that have been reported in migraine with aura. Reaction-diffusion models have been used to model the hallucinations thought to arise from cortical spreading depolarisation and depression in migraine aura. One aim of this review is to make the underlying principles of these models accessible to a general readership. Cortical spreading depolarisation and depression in these models depends on the balance of the diffusion rate between excitation and inhibition, and the occurrence of a large spike in activity to initiate spontaneous pattern formation. We review experimental evidence, including recordings of brain activity made during the aura and attack phase, self-reported triggers of migraine, and psychophysical studies of visual processing in migraine with aura, and how these might relate to mechanisms of excitability that make some people susceptible to aura. Increased cortical excitability, increased neural noise, and fluctuations in oscillatory activity across the migraine cycle are all factors likely to contribute to the occurrence of migraine aura. There remain many outstanding questions relating to the current limitations of both models and experimental evidence. Nevertheless, reaction-diffusion models, by providing an integrative theoretical framework, support the generation of testable experimental hypotheses to guide future research.

The genome sequencing technologies reveal the molecular mechanisms of differentiated thyroid cancer (DTC). Unlike somatic mutation analysis from thyroidectomy samples, germline mutations showing genetic susceptibility to DTC are less understood. The study aimed to assess the prevalence of germline mutations predisposing to DTC in a cohort of Polish individuals based on their whole genome sequencing (WGS) data. We analyzed sequencing data from 1076 unrelated individuals, released openly for academic and clinical research as The Thousand Polish Genomes database (https://1000polishgenomes.com). The list of genes chosen for further analysis was based on the review of previous studies. The cohort contained 104 variants located within the coding and noncoding DNA sequences of 90 genes selected by ClinVar classification as pathogenic and potentially pathogenic. The frequency of variants in the Polish cohort (our study) was compared to the frequency estimated for the non-Finnish European population, obtained from the gnomAD database (gnomad.broadinstitute.org). Statistically significant variants included 23 genes. Even though the Polish population is genetically similar to other European populations, there are significant differences in variant frequencies contributing to the disease development and progression, such as RET, CHECK2, BRCA1, SLC26A4 or TERT. Further studies are needed to identify genomic variants associated directly with DTC.

Set theory faces two difficulties: formal definitions of sets/subsets are incapable of assessing biophysical issues; formal axiomatic systems are complete/inconsistent or incomplete/consistent. To overtake these problems reminiscent of the old-fashioned principle of individuation, we provide formal treatment/validation/operationalization of a methodological weapon termed “outer approach” (OA). The observer’s attention shifts from the system under evaluation to its surroundings, so that objects are investigated from outside. Subsets become just “holes” devoid of information inside larger sets. Sets are no longer passive containers, rather active structures enabling their content’s examination. Consequences/applications of OA include: a) operationalization of paraconsistent logics, anticipated by unexpected forerunners, in terms of advanced truth theories of natural language, anthropic principle and quantum dynamics; b) assessment of embryonic craniocaudal migration in terms of Turing’s spots; c) evaluation of hominids’ social behaviors in terms of evolutionary modifications of facial expression’s musculature; d) treatment of cortical action potentials in terms of collective movements of extracellular currents, leaving apart what happens inside the neurons; e) a critique of Shannon’s information in terms of the Arabic thinkers’ active/potential intellects. Also, OA provides an outer view of a) humanistic issues such as the enigmatic Celestino of Verona’s letter, Dante Alighieri’s “Hell” and the puzzling Voynich manuscript; b) historical issues such as Aldo Moro’s death and the Liston/Clay boxing fight. Summarizing, the safest methodology to quantify phenomena is to remove them from our observation and tackle an outer view, since mathematical/logical issues such as selective information deletion and set complement rescue incompleteness/inconsistency of biophysical systems.

To expand the application area of the reference group and enrich exercise theoretical research, based on Stimulus-Organism-Response (S–O-R) framework, this study examines the factors that motivate for adherence to exercise from the external. Taking reference group and strategy and cultural fit as the main stimulus, and personal investment and life satisfaction as mediating variables, this study try to explore the influence of external stimulus on residents’ exercise behavior. In order to enrich the sample size, two surveys of 734 Chinese residents in two cities (Xiamen vs. Fuzhou) were conducted using factor analyses, regression analysis, and T-test analysis. The results indicated that the reference group and strategic and cultural fit as external stimulus have impact on residents’personal investment, life satisfaction and exercise adherence, personal investment and life satisfaction as the organism has impact on residents’ exercise adherence. Personal investment and life satisfaction play a chain mediating role between the reference group and exercise adherence, strategy and cultural fit, and exercise adherence. Moreover, the T-test determined the differences between Xiamen and Fuzhou residents’ exercise adherence and life satisfaction. Residents’ surroundings affect their exercise behavior and life satisfaction. These findings have implications for policymaking aimed at promoting national exercise, which could gradually improve residents’ physical fitness, particularly in light of the current coronavirus emergency.

Dupilumab is used to treat atopic dermatitis patients who have proven to be refractory to previous treatments. The aim of this study was to assess evolution and patient reported outcome measures in adult patients with moderate-to-severe atopic dermatitis treated with Dupilumab in routine clinical practice. The outcomes were evaluated and registered at baseline and weeks-16, 40 and 52. The variables evaluated were: diseases severity, pruritus, stressful life events, difficulty to sleep, anxiety and depression, quality of life, satisfaction, adherence to the treatment, efficacy and safety. Eleven patients were recruited between Nov 14th 2017 and Jan 16th 2018. Demographic variables: 90% Caucasian, 82% women. Clinical variables: Mean duration of AD =17.7 (±12.8), 91% had severe disease severity. At baseline, SCORAD mean score = 61.7 (±15.5); itch was reported by 100% of patients; itch Visual Analogue Scale mean range of 8 (6-10); HADS mean total score =13.9 (±5.5); DLQI mean score =13.3 (±8.3): EQ-5D-3L mean range = 57 (30-99). At week-52 there is a significant reduction of SCORAD scores, HADS total score and improved quality of life. ¡This study confirms that Dupilumab, used for 52-weeks under routine clinical practice, maintains the improved atopic dermatitis signs and symptoms obtained at week-16, with a good safety profile.