Investigating Carvedilol's Repurposing for the Treatment of Non-Small Cell Lung Cancer via Aldehyde Dehydrogenase Activity Modulation in the Presence of ß-Adrenergic Agonists.

Repurposing existing drugs appears to be a potential solution for addressing the challenges in the treatment of non-small cell lung cancer (NSCLC). ß-adrenoceptor antagonist drugs (ß-blockers) have tumor-inhibiting effects, making them promising candidates for potential NSCLC treatment. This study investigates the anticancer potential of a subset of ß-blockers in NSCLC cell lines; A549 and H1299. Additionally, it investigates the underlying mechanism behind ß-blockers' anticancer effect by influencing a potential novel target named aldehyde dehydrogenase (ALDH). The MTT assay assessed ß-blockers' cytotoxicity on both cell lines, while Western blot and NADH fluorescence assays evaluated their influence on ALDH protein expression and activity. Carvedilol (CAR) was the most effective blocker in reducing cell survival of A549 and H1299 with IC50 of 18 µM and 13.7 µM, respectively. Significantly, CAR led to a 50% reduction in ALDH expression and 80% decrease in ALDH activity in A549 cells, especially when combined with ß-agonists, in comparison to the control. This effect might be attributed to ß-agonist blockade or an alternative pathway. This novel finding adds to our understanding of CAR's multifaceted anticancer properties, implying that combining CAR with ß-agonists could be a useful strategy for lung cancer treatment.

Ultrasound imaging of the phrenic nerve at the scalene muscle level.

The aim of this study is to utilize ultrasound to evaluate the normal cross-sectional area (CSA) of the phrenic nerve (PN), at the level of the anterior scalene muscle. The study included 62 PNs in 31 healthy subjects (13 men, 18 women); mean age, 36.6 years; mean height, 161.1 cm; mean weight, 69.6 kg; and mean body mass index 25.8 kg/m2. High-resolution ultrasound images of the bilateral PNs were obtained by a radiologist with 15 years of experience in neuromusculoskeletal ultrasound. Three separate CSA measurements for the bilateral PNs bilaterally were obtained. Images were also reviewed by an experienced neurologist to evaluate for inter-rater variability. The mean CSA of the right PN was 0.54 mm2 ± 0.16. The mean CSA of the left PN was 0.53 mm2 ± 0.18. We believe that the reference values for the normal CSA of the PNs obtained in our study could help in the sonographic evaluation of PN enlargement, as it relates to the diagnosis of various diseases affecting the PN. Furthermore, knowledge of its location and size, at the level of the scalene muscle, could help prevent PN-related complications during interventional procedures in that area. Additionally, for each participant, demographic information of age and gender as well as body mass index, weight, and height were documented.

The Role of Vitamin E in Protecting against Oxidative Stress, Inflammation, and the Neurotoxic Effects of Acute Paracetamol in Pregnant Female Rats.

Paracetamol (acetaminophen, APAP) is the most common non-prescription analgesic drug used during pregnancy. The aim of this study was to investigate the effect of vitamin E on acute APAP toxicity in pregnant rats. Toxicity in the liver, kidney, and brain (hippocampus, cerebellum, and olfactory bulb) was examined. Twenty pregnant female Wistar rats at gestational day 18 were used. Pregnant rats were divided into four groups: Control, APAP, E + APAP, and APAP + E. The Control group was treated with 0.5 mL p.o. corn oil. The APAP group received 3000 mg/kg p.o. APAP. The E + APAP group received 300 mg/kg p.o. vitamin E one hour before 3000 mg/kg APAP. The APAP + E group received 3000 mg/kg paracetamol one hour before 300 mg/kg p.o. vitamin E. Twenty-four hours after the last treatment administration, rats were euthanized and blood, brain, liver, and kidney samples were collected. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), creatinine levels, uric acid (UA), and superoxide dismutase (SOD) levels, as well as the relative mRNA expression of Cyp1a4, Cyp2d6, and Nat2, were determined. Acute APAP treatment upregulated ALT, AST, BUN, and creatinine levels. APAP treatment downregulated UA and SOD levels. APAP treatment upregulated the relative mRNA expression of Cyp1a4 and Cyp2d6, but downregulated Nat2 expression. Vitamin E treatment, either before or after APAP administration, attenuated the toxic effects of APAP. In conclusion, the results showed that an acute toxic APAP dose in late pregnancy can cause oxidative stress and dysregulation in Cyp isoform expression, and that vitamin E treatment attenuates these effects.

Feelings of Polish and Palestinian Students after Receiving Vaccinations against COVID-19.

The COVID-19 pandemic has limited human freedom in many areas. Developing a COVID-19 vaccine has been a key task to contain the spread of the virus. In many countries, there is increasing concern about anti-vaccines due to complications after receiving the vaccine. The research problem concerns the opinions of Polish and Palestinian students after receiving vaccinations against COVID-19. This study involved 657 respondents (332 from Poland and 325 from Palestine) who completed the original questionnaire online. The respondents present two different cultures, embedded in different existential conditions, also in terms of health care, and especially the availability of vaccines. The obtained data indicate that almost 50% of research participants from both countries believe that vaccines are an effective antidote to the pandemic situation. Respondents in both populations believed that it was their personal choice to undergo vaccinations. The social motivation for vaccination in both groups was the desire to participate in public life, and the possibility of free travel for Poles, and the fear of infecting other people for Palestinians. The most common side effect reported after vaccination was pain at the site of the infection. Medical assistance was more often sought by respondents from Palestine. From an existential, psychosocial and health perspective, vaccines contributed to strengthening the vital forces in a large part of the population, allowed rebuilding social interactions and gave a sense of security in the daily functioning of a person.

Attitudes of Palestinian and Polish Medical Students Towards Death.

Attitudes of students of health-related subjects towards the death are an important issue showing the behaviour and values ​​that guide young people in everyday interactions. The study was conducted using the Questionnaire About Attitudes Against Death (DAP-R-PL) among 309 students, including 150 Palestinian from the Faculty of Nursing and Health Sciences and 159 Polish from the Faculty of Health Sciences. It was noticed that the attitude of Death Avoidance is higher in Palestinians than in Poles. The biggest difference between correlation indicators is for the factors fear of death and death avoidance (FD and DA). This value is positive for Palestinian respondents and negative for Polish respondents. The study confirms that the attitudes of students towards death from both universities in the perspective of 5 factors are positive and in future contacts with dying patients they will cope with this challenge.

Is lactate lower in septic patients who are prescribed beta blockers? Retrospective cohort study of an intensive care population.

OBJECTIVE: Elevated serum lactate has long been considered an important marker of sepsis severity. Increasing evidence supports catecholamine-stimulated aerobic glycolysis being a major contributor to the hyperlactataemia seen in sepsis. Beta-blockade may blunt such catecholamine mediated rise in lactate analogous to the way it can mask tachycardia. This could impact the way we evaluate sepsis severity and adequacy of initial treatment. The objective of this study is to investigate whether septic patients who were on beta-blocker treatment at presentation have lower serum lactate level. METHODS: Using a retrospective cohort design we gathered data on patients admitted to our base hospital intensive care unit with APACHE III diagnosis of sepsis and septic shock during the 2017 calendar year. Serum lactate, current medications, presenting vital signs, illness severity scores, laboratory data and mortality outcome were extracted from patients' medical record and the unit's clinical database. RESULTS: Of 189 records analysed, 49 patients were concurrently prescribed beta-blockers. More beta-blocked patients were male, beta-blocked patients were older, and a greater proportion of beta blocked patients had their first lactate measured as an inpatient. After regression to correct for identified significant covariates mean serum lactate was 0.87 (95% confidence interval 0.05-1.69) mmol/L lower in those prescribed beta blockers. CONCLUSIONS: In our cohort pre-existing beta blocker treatment was associated with lower serum lactate measurements in patients presenting with sepsis. Pre-existing beta blocker treatment may reduce serum lactate at presentation in patients with sepsis.

Smoking Patterns and Willingness to Quit: A Cross-sectional Study in Al Ain City, UAE.

BACKGROUND: Tobacco use is the major cause of preventable morbidity and mortality. The main objectives of this study were to identify smokers willing to participate in quit smoking campaigns using social media and to identify smoking habits of everyday smokers in Al Ain City, United Arab Emirates (UAE). RESEARCH DESIGN AND METHODS: Everyday smokers from Al Ain city of the UAE were surveyed in different locations of the city including malls and specialized tobacco-selling shops. They were interviewed using a semi-structured survey and the information was recorded by one assessor. The information gathered included type and frequency of tobacco use, smoking history and habits, quitting history, desire to quit, and the preferred communication platform. RESULT: A total of 412 regular adult smokers were interviewed in which the majority (95%) reported first smoking at or before the age of 28 years. Participants were mainly UAE nationals (33.7%), Egyptians (14.1%), Syrians (12.9%), and Jordanians (10.9%). Manufactured cigarettes were the main form of tobacco consumption (59.5%), and smoking was mainly solitary (56.3%) and at home (26.3%) and coffee shops (24.9%). The majority of interviewed subjects (76.7%; 95% confidence interval [CI]: 72.4%-80.5%) expressed their interest to quit smoking in the future and 55.3% (95% CI: 50.5%-60.2%) were ready to get involved immediately in a smoking cessation program. Of those, 80.3% (95% CI: 74.6%-84.9%) preferred WhatsApp for receiving smoking cessation motivational education. CONCLUSION: The majority of smokers started at younger ages, which warrant the age of smoking restriction to be raised to 29 years instead of 18 years by the health authority. Everyday smokers were aware of the potentially hazardous effects of tobacco smoking and many were willing to accept help to quit smoking that involves the use of WhatsApp.

Important cellular targets for antimicrobial photodynamic therapy.

The persistent problem of antibiotic resistance has created a strong demand for new methods for therapy and disinfection. Photodynamic inactivation (PDI) of microbes has demonstrated promising results for eradication of antibiotic-resistant strains. PDI is based on the use of a photosensitive compound (photosensitizer, PS), which upon illumination with visible light generates reactive species capable of damaging and killing microorganisms. Since photogenerated reactive species are short lived, damage is limited to close proximity of the PS. It is reasonable to expect that the larger the number of damaged targets is and the greater their variety is, the higher the efficiency of PDI is and the lower the chances for development of resistance are. Exact molecular mechanisms and specific targets whose damage is essential for microbial inactivation have not been unequivocally established. Two main cellular components, DNA and plasma membrane, are regarded as the most important PDI targets. Using Zn porphyrin-based PSs and Escherichia coli as a model Gram-negative microorganism, we demonstrate that efficient photoinactivation of bacteria can be achieved without detectable DNA modification. Among the cellular components which are modified early during illumination and constitute key PDI targets are cytosolic enzymes, membrane-bound protein complexes, and the plasma membrane. As a result, membrane barrier function is lost, and energy and reducing equivalent production is disrupted, which in turn compromises cell defense mechanisms, thus augmenting the photoinduced oxidative injury. In conclusion, high PDI antimicrobial effectiveness does not necessarily require impairment of a specific critical cellular component and can be achieved by inducing damage to multiple cellular targets.

Factors associated with low screening for breast cancer in the Palestinian Authority: relations of availability, environmental barriers, and cancer-related fatalism.

BACKGROUND: The current study was conducted to assess screening behaviors in relation to cultural and environmental barriers among Palestinian women in the West Bank. METHODS: The participants were 397 women, ages 30 to 65 years, residing in the Palestinian Authority, and a stratified sample method was used (98.3% participation rate). The participants completed questionnaires on breast examination behaviors and knowledge, on perceived cancer fatalism and health beliefs, and on environmental barriers scales. RESULTS: Greater than 70% of the women had never undergone mammography or clinical breast examination (CBE), whereas 62% performed self breast examination (SBE). Women were more likely to undergo mammography if they were less religious (odds ratio [OR], 0.59; 95% confidence interval [95% CI], 0.47-0.81) and if they expressed lower personal barriers (OR, 0.59; 95% CI, 0.29-0.76) and lower fatalism (OR, 0.39; 95% CI, 0.28-0.63). A higher likelihood for CBE was related to being Christian (OR, 2.91; 95% CI, 1.49-5.73) and being less religious (OR, 0.32; 95% CI, 0.13-0.78), to perceived higher effectiveness of CBE (OR, 1.46; 95% CI, 1.20-1.79), and to perceived lower cancer fatalism (OR, 0.35; 95% CI, 0.28-0.60). Women were more likely to perform SBE if they were more educated, resided in cities, were Christian, were less religious, had a first-degree relative with breast cancer, perceived higher effectiveness and benefits of SBE, and perceived lower barriers and fatalism. CONCLUSIONS: Participants reported a combination of personal, cultural, and environmental barriers, which should be addressed by educational programs and followed by the allocation of resources for early detection and treatment of breast cancer.