Synthesis of new hybrid quinazoline compounds as antiproliferative agents for breast and colon cancer treatment

Purpose: To evaluate newly synthesized fuoryl quinazoline derivatives for antitumor efficacy.Methods: Fuoryl quinazoline derivatives were synthesized and the structures of the synthesized compounds were characterized using standard techniques. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) technique was used to assess the anti-proliferative properties of the synthesized derivatives in vitro.Results: All quinazoline compounds displayed cytotoxic activity against breast and colon cancer cell lines to varying degrees. Compound IXa with acetohydrazide moiety was the most effective on MCF7 and HCT116 cell lines, with half-maximal inhibitory concentration (IC50) values of 16.70 and 12.54 μM, respectively.Conclusion: N'-benzylidene-2-((2-(furan-2-yl) quinazolin-4-yl) oxy) acetohydrazide IXa showed the strongest anti-proliferative activity against MCF-7 and HCT116 human cancer cell lines

Correlation between the severity of COVID-19 vaccine-related adverse events and the blood group of the vaccinees in Saudi Arabia: A web-based survey

Background: Recent epidemiological studies have reported an association between the ABO blood group and the acquisition, symptom severity, and mortality rate of coronavirus disease 2019 (COVID-19). However, the association between the ABO blood group antigens and the type and severity of COVID-19 vaccine-related adverse reactions has not been elucidated.Patients and Methods: We conducted a cross-sectional, questionnaire-based study in Saudi Arabia from February to April 2022. The study cohort included adults who had received or were willing to receive at least two doses of a COVID-19 vaccine of any type. We used Chi-square test to assess the association between the ABO blood groups and vaccine-related adverse reactions. p values of <0.05 were considered significant.Results: Of the 1180 participants, approximately half were aged 18–30 years old, 69.2% were female, and 41.6% reported their blood group as O. The most frequent COVID-19 vaccine-related adverse reactions were fatigue (65%), pain at the injection site (56%), and headache (45.9%). These adverse reactions demonstrated significant correlations with the education level (p = 0.003) and nationality (p = 0.018) of the participants following the first dose, with gender (p < 0.001) following the second dose, and with the general health status (p < 0.001) after all the doses. Remarkably, no correlation was observed between the severity of the vaccine-related adverse reactions and ABO blood groups.Conclusion: Our findings do not support a correlation between the severity of COVID-19 vaccine-related adverse reactions and the ABO blood groups of the vaccinees. The creation of a national database is necessary to account for population differences

Anticancer effects of punicalagin and 5-fluorouracil on laryngeal squamous cell carcinoma: an <i>in vitro</i> study

The purpose of this study was to assess the apoptotic effects of punicalagin alone and in combination with 5-fluorouracil (5-FU) on laryngeal squamous cell carcinoma (Hep-2) cell line. Hep-2 cells were cultured and divided into four groups: Group 1 received no therapy and served as control, Group 2 received 5-FU only, Group 3 received punicalagin only, and Group 4 received a combination of 5-FU and punicalagin. After 48 hours of incubation, cellular changes were examined under an inverted microscope. The methyl thiazolyl tetrazolium assay, caspase-3 gene level, and vascular endothelial growth factor (VEGF) level were assessed. The control group showed the highest mean value of cancer cell proliferation rate (1.595±0.58), followed by the punicalagin group (1.263±0.447), then the 5-FU group (0.827±0.256), while the combination group showed the lowest proliferation rate (0.253±0.111). The combination group showed the highest mean value of caspase-3 concentration (3.177±0.736), followed by the 5-FU group (1.830±0.646), and punicalagin group (0.741±0.302), while the control group showed the lowest mean value (0.359±0.117). Regarding VEGF levels, the control group had a statistically significant higher mean value, followed by the punicalagin and 5-FU groups, and finally, the combination group which showed the lowest value. Punicalagin exerts an anticancer effect through anti-proliferative action and induction of apoptosis on Hep-2 cell line. Combining punicalagin with 5-FU potentiates its anti-proliferative, apoptotic, and anti-angiogenic actions. It, further, helps in mitigating the putative side effects of 5-FU by reducing the dose required for its therapeutic effects

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Travel burden and clinical presentation of retinoblastoma: analysis of 1024 patients from 43 African countries and 518 patients from 40 European countries

BACKGROUND: The travel distance from home to a treatment centre, which may impact the stage at diagnosis, has not been investigated for retinoblastoma, the most common childhood eye cancer. We aimed to investigate the travel burden and its impact on clinical presentation in a large sample of patients with retinoblastoma from Africa and Europe. METHODS: A cross-sectional analysis including 518 treatment-naïve patients with retinoblastoma residing in 40 European countries and 1024 treatment-naïve patients with retinoblastoma residing in 43 African countries. RESULTS: Capture rate was 42.2% of expected patients from Africa and 108.8% from Europe. African patients were older (95% CI -12.4 to -5.4, p<0.001), had fewer cases of familial retinoblastoma (95% CI 2.0 to 5.3, p<0.001) and presented with more advanced disease (95% CI 6.0 to 9.8, p<0.001); 43.4% and 15.4% of Africans had extraocular retinoblastoma and distant metastasis at the time of diagnosis, respectively, compared to 2.9% and 1.0% of the Europeans. To reach a retinoblastoma centre, European patients travelled 421.8 km compared to Africans who travelled 185.7 km (p<0.001). On regression analysis, lower-national income level, African residence and older age (p<0.001), but not travel distance (p=0.19), were risk factors for advanced disease. CONCLUSIONS: Fewer than half the expected number of patients with retinoblastoma presented to African referral centres in 2017, suggesting poor awareness or other barriers to access. Despite the relatively shorter distance travelled by African patients, they presented with later-stage disease. Health education about retinoblastoma is needed for carers and health workers in Africa in order to increase capture rate and promote early referral

The global retinoblastoma outcome study : a prospective, cluster-based analysis of 4064 patients from 149 countries

DATA SHARING : The study data will become available online once all analyses are complete.BACKGROUND : Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. METHODS : We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. FINDINGS : The cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0–36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8–100·0) for children from high-income countries, 91·2% (89·5–93·0) for children from upper-middle-income countries, 80·3% (78·3–82·3) for children from lower-middle-income countries, and 57·3% (52·1-63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76–50·00), cT4 advanced tumour compared to cT1 (8·98; 4·44–18·18), and older age at diagnosis in children up to 3 years (1·38 per year; 1·23–1·56). For children aged 3–7 years, the mortality risk decreased slightly (p=0·0104 for the change in slope). INTERPRETATION : This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes.The Queen Elizabeth Diamond Jubilee Trust and the Wellcome Trust.https://www.thelancet.com/journals/langlo/homeam2023Paediatrics and Child Healt

Prevalence of bacteriological and parasitological causes of diarrheic calves in middle Egypt

Neonatal calf diarrhea (NCD), is one of the prime fundamental health issues facing the cattle industry, and has resulted in significant economic losses. This study aimed at detection of the enteric pathogens in diarrheic calves. Another objective was to correrlate the existence of isolated enteric pathogens to the age and seasonal distribution of diarrheic parasitic and bacterial infections among calves. The bacterial isolates were identified biochemically and serologically. Moreover the samples were examined macro and microscopically to investigate the internal parasitic causes of diarrhea. Also, for Cryptosporidium spp. Oocysts were diagnosed using modified Ziehl-Neelsen stained smears. Out of 364 collected fecal samples, a total bacteria isolated was 356 and identified as 131 Escherichia coli (35.99%), 90 Salmonella enterica (24.72%); 50 S. typhimurium (13.73%) and 40 S. dublin (10.99%), 35 Citrobacter diversus (9.61%), 24 Klebsiella pneumonia (6.59%), 20 P. vulgaris (5.49%), 19 P. penneri (5.22%) and 37 Staphylococcous aureus (10.16%). Regarding the parasitological findings; Toxocara vitulorum was 19.8% (72 out of 364), Oocysts of Eimeria spp. were found in 26.9% (98/364), Cryptosporidium spp. was 29.4% (107 out of 364) and Giardia spp. infection was 14% (51 out of 364). In conclusion, NCD problem is a multifactorial in which bacterial and parasitological causes were the prime causes. Thus, regular monitoring and efficient treatment of bacteriological and parasitological causes of NCD are highly recommended