Experiment data: Human-in-the-loop decision support in process control rooms.

These datasets contain measures from multi-modal data sources. They include objective and subjective measures commonly used to determine cognitive states of workload, situational awareness, stress, and fatigue using data collection tools such as NASA-TLX, SART, eye tracking, EEG, Health Monitoring Watch, a survey to assess training, and a think-aloud situational awareness assessment following the SPAM methodology. Also, data from a simulation formaldehyde production plant based on the interaction of the participants in a controlled control room experimental setting is included. The interaction with the plant is based on a human-in-the-loop alarm handling and process control task flow, which includes Monitoring, Alarm Handling, Recovery planning, and intervention (Troubleshooting, Control and Evaluation). Data was collected from 92 participants, split into four groups while they underwent the described task flow. Each participant tested three scenarios lasting 15-18 min with a -10-min survey completion and break period in between using different combinations of decision support tools. The decision support tools tested and varied for each group include alarm prioritisation vs. none, paper-based vs. Digitised screen-based procedures, and an AI recommendation system. This is relevant to compare current practices in the industry and the impact on operators' performance and safety. It is also applicable to validate proposed solutions for the industry. A statistical analysis was performed on the dataset to compare the outcomes of the different groups. Decision-makers can use these datasets for control room design and optimisation, process safety engineers, system engineers, human factors engineers, all in process industries, and researchers in similar or close domains.

Prevalence and Risk Factors of Deep Vein Thrombosis Among Adult Surgical Patients in Aseer Central Hospital, Saudi Arabia.

INTRODUCTION: Deep vein thrombosis (DVT) is a medical disorder that arises when a coagulation of blood forms in a deep vein, entirely or partially blocking veins, and commonly affects the lower limb. The occurrence is fairly common worldwide and it is said to increase with age, with males being at a higher risk than females. OBJECTIVE: This study aims to determine the prevalence and risk factors of DVT among adult surgical patients in Aseer Central Hospital in the Aseer Region of Saudi Arabia. METHODS: This is a cross-sectional study involving 602 adult surgical patients hospitalized in the Aseer Central Hospital. Self-administered questionnaires were used to collect data from the respondents, and the data collected were analyzed using IBM SPSS Statistics for Windows, Version 24.0 (Released 2016; IBM Corp., Armonk, New York, United States). Statistical tests of association were used among the categorical variables. Association between variables was considered significant when p-value was less than 0.05. Binary logistic regression was performed to eliminate the effect of confounders in determining the risk factors for developing DVT among the respondents. RESULTS: The questionnaire response rate was 100%, with the mean age of the respondents being 44.2 ± 19.7 years. The prevalence of DVT was 7% (n=42). Obesity with adjusted OR (aOR) 17.9 (95%CI =5.39-59.18), hypertension with aOR 0.3 (95%CI =0.08-1.03), ischemic heart disease with aOR4.5 (95%CI =1.18-16.83), and orthopedics aOR 0.1 (95%CI=0.013-.240) were found to be independent risk factors for developing DVT among the respondents (p-value <=0.05). Other variables like diabetes, contraception, and pregnancy were not statistically associated with the development of DVT (p-value> 0.05) in these respondents. CONCLUSION: The findings of this study indicated a significantly low prevalence in comparison to Saudi Arabian research. Key risk factors included obesity (18x higher risk), ischemic heart disease, and hypertension. Surgery location, orthopedic cast, and Doppler ultrasound also influenced risk, while age and sex weren't significant predictors.

Gabapentin-Induced Myoclonus in a Patient With Chronic Kidney Disease.

Gabapentin contains a cyclohexyl group and is a form of gamma-aminobutyric acid (GABA). Despite its name, gabapentin does not affect the inhibitory neurotransmitter GABA or its receptors. Instead, it acts as a ligand, binding strongly to the α2δ (Ca) channel subunit and interfering with its regulatory function and the release of excitatory neurotransmitters. Gabapentin is approved by the FDA for treating seizure disorders and neuropathic pain, except for trigeminal neuralgia. However, it is frequently used off-label to treat other pain conditions and psychological disorders, such as anxiety. Unlike other drugs, gabapentin is not metabolized in the liver and is solely excreted by the kidneys. Therefore, it is crucial to adjust the dosage in patients with renal insufficiency to avoid severe adverse effects. In this case report, we present a patient with chronic renal impairment who experienced devastating myoclonic jerky movements shortly after increasing his gabapentin dose.

Breast cancer with scalp metastases: a case report.

BACKGROUND: While breast cancer is the most common cancer in women, cutaneous metastases are rare in breast cancer. Additionally, scalp involvement in breast cancer metastasis is extremely rare. That being said, scalp lesions should always be thoroughly investigated to distinguish metastatic lesions from other neoplasms. CASE PRESENTATION: A 47-year-old female Middle-Eastern patient presented with metastatic breast cancer in the lungs, bone, liver, and brain with no signs of multiple organ failure, in addition to cutaneous metastases, including the scalp. Between 2017 and 2022, she was managed through modified radical mastectomy, radiotherapy, and several lines of chemotherapy. She presented in September of 2022 with enlarging scalp nodules, which started developing 2 months prior to her presentation. Physical examination revealed firm, non-tender, and immobile skin lesions. Magnetic resonance imaging scan of the head showed soft tissue nodules in different sequences. A punch biopsy was taken from the largest scalp lesion and showed metastatic invasive ductal carcinoma. A panel of immunohistochemistry stains was applied, because a single specific marker for differentiating primary cutaneous adnexal tumors or other malignant neoplasms from breast cancer has not yet been identified. The panel showed positive estrogen receptor 95%, progesterone receptor 5%, negative human epidermal growth factor receptor 2, positive GATA binding protein 3, positive cytokeratin-7, negative P63, and negative KIT (CD117). CONCLUSION: Breast cancer metastases to the scalp are extremely uncommon. When a scalp metastasis is present, it might be the only symptomatic sign of disease progression or widespread metastatic lesions. However, such lesions warrant a comprehensive radiologic and pathologic workup to rule out other possibilities of skin pathologies, such as sebaceous skin adenocarcinoma as it effects the management plan.

Prediction of the Bending Strength of a Composite Steel Beam-Slab Member Filled with Recycled Concrete.

This study investigated the structural behavior of a beam-slab member fabricated using a steel C-Purlins beam carrying a profile steel sheet slab covered by a dry board sheet filled with recycled aggregate concrete, called a CBPDS member. This concept was developed to reduce the cost and self-weight of the composite beam-slab system; it replaces the hot-rolled steel I-beam with a steel C-Purlins section, which is easier to fabricate and weighs less. For this purpose, six full-scale CBPDS specimens were tested under four-point static bending. This study investigated the effect of using double C-Purlins beams face-to-face as connected or separated sections and the effect of using concrete material that contains different recycled aggregates to replace raw aggregates. Test results confirmed that using double C-Purlins beams with a face-to-face configuration achieved better concrete confinement behavior than a separate configuration did; specifically, a higher bending capacity and ductility index by about +10.7% and +15.7%, respectively. Generally, the overall bending behavior of the tested specimens was not significantly affected when the infill concrete's raw aggregates were replaced with 50% and 100% recycled aggregates; however, their bending capacities were reduced, at -8.0% and -11.6%, respectively, compared to the control specimen (0% recycled aggregates). Furthermore, a new theoretical model developed during this study to predict the nominal bending strength of the suggested CBPDS member showed acceptable mean value (0.970) and standard deviation (3.6%) compared with the corresponding test results.

Immunological and histopathological evaluation of Eimeria tenella oocysts Egyptian local isolate vaccine and its comparative efficacy with a commercial live vaccine.

Coccidiosis is the most important protozoan disease in broilers all over the world. Controlling of broilers coccidiosis via vaccination rather than chemicals is a new trend with promising results. Thus, the present work describes an evaluation of Eimeria tenella Lab-made vaccine of local Egyptian strain and its comparative efficacy with a commercial live vaccine "Fortegra®". Eighty broiler chickens one day old were used; they were divided in to 4 equal groups; 20 chicks each. Group 1 (G1) kept as control negative, G2 administrated orally with lab-made sporulated oocysts vaccine at 5 days old, the birds of G3 vaccinated orally with Fortegra® at day 6 of age, and G4 served as control positive. All birds were challenge by 50,000 sporulated oocysts of E. tenella at day 21. For testing the efficacy and comparison; OPG (oocyst per gram), serum Interleukin4 (IL4) levels, Immunoglobulin A (IgA) levels in both serum and ceca, cecal lesion score, as well as histopathological changes in ceca of tested groups were evaluated. The results demonstrated significantly elevated IL4 level in serum and IgA level in serum and cecum of G2 than G3. IgA in cecum significantly elevated in G2 than G3. OPG significantly decreased in both vaccinated groups (G2 and G3), and have lower lesion score than nonimmunized group. Cecal tissues of vaccinated groups had mild pathological changes. Conclusively, good immunization by the currently tested vaccine, against experimental E. tenella infection was observed.

Immunological and histopathological evaluation of Eimeria tenella oocysts Egyptian local isolate vaccine and its comparative efficacy with a commercial live vaccine

@#Coccidiosis is the most important protozoan disease in broilers all over the world. Controlling of broilers coccidiosis via vaccination rather than chemicals is a new trend with promising results. Thus, the present work describes an evaluation of Eimeria tenella Lab-made vaccine of local Egyptian strain and its comparative efficacy with a commercial live vaccine “Fortegra®”. Eighty broiler chickens one day old were used; they were divided in to 4 equal groups; 20 chicks each. Group 1 (G1) kept as control negative, G2 administrated orally with lab-made sporulated oocysts vaccine at 5 days old, the birds of G3 vaccinated orally with Fortegra® at day 6 of age, and G4 served as control positive. All birds were challenge by 50,000 sporulated oocysts of E. tenella at day 21. For testing the efficacy and comparison; OPG (oocyst per gram), serum Interleukin4 (IL4) levels, Immunoglobulin A (IgA) levels in both serum and ceca, cecal lesion score, as well as histopathological changes in ceca of tested groups were evaluated. The results demonstrated significantly elevated IL4 level in serum and IgA level in serum and cecum of G2 than G3. IgA in cecum significantly elevated in G2 than G3. OPG significantly decreased in both vaccinated groups (G2 and G3), and have lower lesion score than nonimmunized group. Cecal tissues of vaccinated groups had mild pathological changes. Conclusively, good immunization by the currently tested vaccine, against experimental E. tenella infection was observed.

Mail-Back Envelopes for Retrieval of Opioids After Pediatric Surgery.

BACKGROUND: Opioid overprescription has the potential to lead to harmful medications remaining in homes and to a rise in accidental or deliberate ingestion by children and adolescents. Although methods for opioid disposal are available, many are costly or require greater than minimal effort for the patient. In this study, we used a mail-back return envelope to retrieve unused opioids after ambulatory pediatric surgery. METHODS: This feasibility study was performed to assess the rate of opioid return by using a mail-back envelope for children ages 0 to 18 prescribed opioids after outpatient surgery. Participants were provided a return envelope as well as instruction on the dangers of opioids in the home. Our primary outcome was to assess the absolute percent return rate through the use of a mail-back envelope. RESULTS: Between November 2017 and October 2018, we identified 355 patients, of whom 331 were included in the analysis. In total, 64 (19.3%) returned opioids. In total, >2000 mL of liquid opioids and >250 tablets or nearly 3000 mg of oral morphine equivalents were removed from the homes of the 64 participants. Of those patients returning unused medications, the median rate of return was 58% (interquartile range = 34.7%-86.1%) of the written prescription. CONCLUSIONS: The findings suggest that providing a free mail-back return envelope is a suitable way to remove unused opioids from the home after pediatric surgery. Additional research is needed to identify barriers to return of unused medications.

Interdisciplinary Mitigation of Opioid Misuse in Musculoskeletal Patients.

BACKGROUND: The opioid prescribing patterns of orthopedic surgeons have been shown to play a role in exacerbating rates of opioid misuse among post-surgical patients. Demonstrable success has been appreciated by combining policy-level approaches and clinical education-based strategies to inform patients of alternative modalities of post-operative analgesia. QUESTIONS/PURPOSES: The purpose of this review was to address two questions: What are the most substantiated measures orthopedic surgeons can take to limit opioid misuse or addiction among their patients? What advantages are gained in orthopedic surgeons' collaborating with other healthcare professionals with influence over patients' post-operative opioid exposure? METHODS: We searched two databases for articles on multidisciplinary policy-based solutions to mitigating the opioid overdose crisis among musculoskeletal patients. Articles produced from the search were searched for further evidence supporting the use of standardized clinical and administrative protocols in mitigating opioid misuse within this patient population. Successful approaches to mitigating misuse of opioids in this demographic were synthesized from recurring themes in the studies. RESULTS: Multiple articles support orthopedic surgeons being aware of the risk factors for chronic opioid use among their patients, as well as multidisciplinary strategies involving orthopedic surgeons and other healthcare/governmental professionals to address the burden of the opioid crisis on surgical patients. CONCLUSIONS: Addressing the misuse of opioids among orthopedic patients requires appropriate prescribing practices and long-term support of patients. Collaboration between surgeons and policymaking entities is recognized as an effective population-wide approach to preventing opioid dependence, misuse, and addiction.

Nuclear factor E2-related factor-2 has a differential impact on MCT1 and MCT4 lactate carrier expression in colonic epithelial cells: a condition favoring metabolic symbiosis between colorectal cancer and stromal cells.

Malignant tumors, such as colorectal cancer (CRC), are heterogeneous diseases characterized by distinct metabolic phenotypes. These include Warburg- and reverse Warburg phenotypes depending on differential distribution of the lactate carrier proteins monocarboxylate transporter-4 and -1 (MCT4 and MCT1). Here, we elucidated the role of the antioxidant transcription factor nuclear factor E2-related factor-2 (Nrf2) as the key regulator of cellular adaptation to inflammatory/environmental stress in shaping the metabolism toward a reverse Warburg phenotype in malignant and premalignant colonic epithelial cells. Immunohistochemistry of human CRC tissues revealed reciprocal expression of MCT1 and MCT4 in carcinoma and stroma cells, respectively, accompanied by strong epithelial Nrf2 activation. In colorectal tissue from inflammatory bowel disease patients, MCT1 and Nrf2 were coexpressed as well, relating to CD68+inflammatory infiltrates. Indirect coculture of human NCM460 colonocytes with M1- but not M2 macrophages induces MCT1 as well as G6PD, LDHB and TALDO expression, whereas MCT4 expression was decreased. Nrf2 knockdown or reactive oxygen species (ROS) scavenging blocked these coculture effects in NCM460 cells. Likewise, Nrf2 knockdown inhibited similar effects of tBHQ-mediated Nrf2 activation on NCM460 and HCT15 CRC cells. M1 coculture or Nrf2 activation/overexpression greatly altered the lactate uptake but not glucose uptake and mitochondrial activities in these cells, reflecting the reverse Warburg phenotype. Depending on MCT1-mediated lactate uptake, Nrf2 conferred protection from TRAIL-induced apoptosis in NCM460 and HCT15 cells. Moreover, metabolism-dependent clonal growth of HCT15 cells was induced by Nrf2-dependent activation of MCT1-driven lactate exchange. These findings indicate that Nrf2 has an impact on the metabolism already in premalignant colonic epithelial cells exposed to inflammatory M1 macrophages, an effect accompanied by growth and survival alterations. Favoring the reverse Warburg effect, these Nrf2-dependent alterations add to malignant transformation of the colonic epithelium.

Validation of an Arabic version of an instrument to measure waterpipe smoking behavior.

OBJECTIVES: Reliable and valid measures of waterpipe smoking are essential to study its health effects. The purpose of this study was to examine the reliability and validity of an Arabic translation of Maziak questionnaire that assesses various aspects of waterpipe smoking in epidemiological studies. STUDY DESIGN: A cross-sectional study. METHODS: This questionnaire was translated, back translated, and culturally adapted to the local Arabic dialect. Construct and convergent validity were assessed in a sample of 119 daily waterpipe smokers (WPS) and 30 occasional WPS, defined as smoking at least one waterpipe per week but less than daily from Beirut and Doha (mean age = 52.4 years, males = 61.7%). Construct validity was assessed by comparing the smoking behavior of daily and occasional WPS. Convergent validity was assessed by correlating daily smoking intensity ('number of waterpipe smoked per day') with 'number of waterpipe smoked yesterday' and by correlating lifetime smoking exposure (waterpipe-year) calculated by multiplying number of waterpipe smoked per day × duration of waterpipe smoking with alternate measures obtained graphically (graphical waterpipe-year) or adjusted (adjusted waterpipe-year). Criterion validity was assessed by correlating daily smoking intensity and lifetime smoking exposure with serum cotinine level. Test-retest reliability was analyzed by re-administering the questionnaire to 30 daily and 30 occasional WPS after 2 weeks. RESULTS: Smoking intensity, patterns of use, and willingness to quit differed significantly between daily and occasional WPS. Daily smoking intensity correlated strongly with the number of waterpipe smoked yesterday (rs = 0.68, P < 0.001), but not in the occasional WPS (rs = 0.13, P = 0.70). Waterpipe-year correlated very strongly with adjusted waterpipe-year and graphical waterpipe-year (rs = 0.98, P < 0.001 and rs = 0.92, P < 0.001, respectively). Waterpipe-year, daily smoking intensity, and number of waterpipe smoked yesterday, correlated weakly but significantly with serum cotinine levels (rs = 0.243, P = 0.01; rs = 0.359, P < 0.01 and rs = 0.387, P < 0.01, respectively). The type and pattern of waterpipe use items showed high test-retest reliability with near perfect agreement (k > 0.9), the sharing and intention to quit waterpipe items had substantial agreement (k > 0.6), and the intent to quit item showed moderate agreement (k > 0.4). CONCLUSION: The questionnaire showed strong reliability, face validity, construct and convergent validity, and a weak but statistically significant criterion validity. Maziak questionnaire is valid and reliable for assessing waterpipe smoking patterns, intensity, and willingness to quit.

Rats' urinary metabolomes reveal the potential roles of functional foods and exercise in obesity management.

The complexity of the metabolic changes in obese individuals still presents a challenge for the understanding of obesity-related metabolic disruptions and for obesity management. In this study, a gas chromatography mass spectrometry (GC-MS) based metabolomics approach targeting urine metabolism has been applied to assess the potential roles of functional foods and exercise for obesity management in rats. Male albino rats diagnosed as obese via histopathology and biochemical assays were administered functional foods in common use for obesity management including pomegranate, grapefruit, and red cabbage juice extracts in parallel with swimming exercise. Urine samples were collected from these rats, and likewise from healthy control animals, for metabolite analysis using (GC-MS) coupled to multivariate data analysis. The results revealed a significant elevation in oxalate and phosphate levels in obese rat urine concurrent with lower lactate levels as compared to the control group. Furthermore, and to pinpoint the bioactive agents in the administered functional foods, ultra performance liquid chromatography (UPLC) coupled to high resolution time-of-flight mass spectrometry (TOF-MS) was employed for secondary metabolite profiling. The different phenolic classes found in the examined functional foods, viz. ellagitannins in pomegranate, flavanones in grapefruit and flavonols in red cabbage, are likely to mediate their anti-obesity effects. The results indicate that these functional foods and exercise were quite effective in reverting obesity-related metabolic disruptions back to normal status, as revealed by orthogonal partial least squares-discriminant analysis (OPLS-DA).

Estrogenic Activity Including Bone Enhancement and Effect on Lipid Profile of Luteolin-7-O-glucoside Isolated from Trifolium alexandrinum L. in Ovariectomized Rats.

Luteolin-7-O-glycoside (LG), an abundant component in many edible plants, was found to be one of the major constituents of the aqueous methanol extract of Trifolium alexandrinum L. family Fabaceae, a fodder plant widely cultivated in Egypt. The estrogenic activity of LG concerning the effect on uterotrophy, lipid profile, weight gain and bone enhancement activity was determined in ovariectomized rat model at a dose of 5 mg/kg. Luteolin-7-O-glycoside showed significant estrogenic effect through the preservation of normal uterine weight and plasma estradiol level. It also significantly inhibited the bone turnover markers plasma bone-specific alkaline phosphatase, plasma osteocalsin, type I procollagen N-terminal, and C-telopeptide of type II collagen levels. It induced a significant improvement in plasma lipid profile. The effect of LG was comparable with estradiol with lower effect on uterine weight. Liver and kidney functions revealed a wide safety of LG at this dose level. The present study revealed that LG may be a promising hormone replacement therapy after being examined thoroughly on human. Copyright © 2016 John Wiley & Sons, Ltd.

HIV/AIDS awareness among Iraqi medical and dental students.

OBJECTIVES: The present study investigated the awareness of HIV/AIDS among medical and dental students in four provinces of Iraq, a country with low HIV/AIDS frequency. MATERIALS AND METHODS: In the present study, the target population was all Iraqi medical and dental students who were in 3(rd) and 4(th) year of their education. Out of 15 medicine and 10 dentistry faculties in Iraq, 4 medical and dental faculties were randomly selected. All the students under them were invited to participate in the study (600 students) and 526 responses were received from them. We distributed the questionnaires to students during their obligatory lectures in the academic year 2012-2013. Data collection was done with a self-administered questionnaire containing knowledge and attitude questions (11 questions for each part) in addition to some demographic questions. RESULTS: A total of 526 questionnaires were received (from 319 medical students and 207 dental students). Knowledge of about half of the medical students (54%) was at an intermediate level and of 27.1% students was at a good level; more than half of the dental students (68.2%) had an intermediate level and 10.5% had a good level of knowledge. The level of attitude of medical students was 14.7% at an intermediate level and of dentistry students was 21.4% at an intermediate level. Attitude of none of the students was at good level. Knowledge and attitude scores were not significantly associated with age, gender, or marital status. However, medical students had better knowledge and attitude toward HIV/AIDS, compared to dental students. CONCLUSIONS: Some coefficients exist in knowledge and attitude of Iraqi medical and dental students toward HIV/AIDS. Results indicate that more emphasis should be placed on educating dental and medical students about HIV and other blood-borne infections.

Does a rapid diagnosis of Clostridium difficile infection impact on quality of patient management?

A rapid and accurate diagnosis of Clostridium difficile infection (CDI) is essential for patient management and implementation of infection control measures. During a prospective time-series study, we compared the impact of three different diagnostic strategies on patient care. Each strategy was tested during a 3-month period: P1 (diagnosis based on the stool cytotoxicity assay and the toxigenic culture), P2 (diagnosis based on PCR) and P3 (two-step algorithm based on glutamate dehydrogenase detection followed by nucleic acid amplification test). The following criteria were used to assess the quality of patient management: (i) time for result reporting, (ii) frequency of repeat testing within 7 days, (iii) time elapsed between stool collection and beginning of treatment for patients with CDI, and (iv) frequency of empirical treatment for patients without CDI. Of 1122 stool samples (P1 n = 359, P2 n = 374, P3 n = 389), 36 (10.0%), 47 (12.3%) and 48 (12.3%) were positive for C. difficile during P1, P2 and P3, respectively. The time for reporting of a positive or a negative result was significantly shorter and the frequency of redundant stool samples within 7 days was lower during P2 and P3 than during P1. Patients with CDI were specifically treated with vancomycin or metronidazole earlier during P2 and P3 than patients from P1 (0.5 ± 0.5 days and 1.0 ± 1.8 days vs. 2.0 ± 1.7 days). The empirical therapy among patients without CDI decreased from 13.6% during P1 to 6.4% during P2 and 5.6% during P3. A rapid CDI diagnosis impacts positively on patient care.

Trajectories of intimate partnerships, sexual attitudes, desire and satisfaction.

This research addresses the interrelations existing between trajectories of intimate partnerships and attitudes toward sexuality, sexual desire, and sexual satisfaction. It is based on a dataset of 600 adults aged 25-46 living in Geneva (Switzerland) and uses innovative multivariate techniques for clustering life trajectories. The results emphasize the diversity of men's and women's trajectories of intimate partnerships. Trajectories with frequent and short-term partnerships are associated with recreational attitudes and higher solitary and dyadic sexual desire. In contrast, trajectories featuring few or no intimate partnerships are associated with traditional sexual attitudes and less sexual desire. Women's attitudes toward sexuality are more strongly associated with their intimate trajectories than men's. This suggests that men and women do not develop their sexuality in the same relation with intimacy. The results are referred to the gendered master status hypothesis.

Synthesis, antitumor, cytotoxic and antioxidant evaluation of some new pyrazolotriazines attached to antipyrine moiety.

Iminopropanehydrazonoyl cyanide 4 was achieved upon reaction of antipyrine diazonium salt 2 with 3-iminobutanenitrile (3) in EtOH/AcONa. 3-Aminopyrazole derivative 5 was obtained upon reaction of 4 with hydrazine hydrate. Diazodization of 5 afforded the diazonium salt 6 which coupled with active methylene compounds 7-10, 19, 20, 25, 29 and 32 in pyridine to give aryl hydrazone derivatives 11-14, 21, 22, 26, 30 and 33, respectively. Refluxing of compounds 11-14, 21, 22, 26 and 33 in acetic acid afforded the pyrazolotriazines 15-18, 23, 24, 28 and 35, respectively. The newly synthesized compounds were screened for their cytotoxic and antioxidant activities. The results showed clearly that compounds 4, 5, 13, 22, and 24 displayed promising in vitro anticancer activity against four different cell lines (HepG2, WI 38, VERO and MCF-7). Compounds 4 and 22 are the more potent antioxidant and anticancer agents. On the other hand, most of the compounds exhibited good cytotoxic activity toward (EAC).

The effect of nicotine on anti-vascular endothelial growth factor therapy in a mouse model of neovascular age-related macular degeneration.

PURPOSE: The purpose of this article is to evaluate the effect of nicotine on anti-vascular endothelial growth factor therapy in the treatment of neovascular age-related macular degeneration. METHODS: One group of mice received nicotine in drinking water and the other group received water only. Choroidal neovascularization (CNV) was induced with a laser. Nicotinic acetylcholine receptor-α7 (nAChRα7) expression was evaluated by immunohistochemistry. Bevacizumab or adiponectin peptide II (APNpII) was injected intravitreally on Day 7 postlaser, and the effects were evaluated on Days 14 and 21. α-Bungarotoxin was injected intraperitoneally on Days 2 to 5, and its effect was evaluated on Day 14. RESULTS: Expression of nAChRα7 was 2 to 7 times higher between Days 3 and 7 postlaser compared with naive mice. In water-fed mice, APNpII, bevacizumab, and α-bungarotoxin significantly reduced CNV size. In nicotine-fed mice, treatment with APNpII or bevacizumab did not significantly reduce CNV size, whereas α-bungarotoxin did have an effect. Comparing water- and nicotine-fed mice, CNV size was 61% to 86% smaller in water-fed mice except for the α-bungarotoxin group, where there was no difference. Platelet-derived growth factor and vascular endothelial growth factor expression was 1.5- to 2.5-fold higher at Day 14 in nicotine-treated mice. CONCLUSION: Nicotine significantly blocks the effect of anti-vascular endothelial growth factor therapy in the treatment of laser-induced neovascular age-related macular degeneration. nAChRα7 is significantly upregulated during the formation of CNV, and treatment with an nAChRα7 antagonist decreases CNV size irrespective of nicotine administration.