The role of CXCL1 in crosstalk between endocrine resistant breast cancer and fibroblast.

BACKGROUND: ER positive breast cancer is currently targeted using various endocrine therapies. Despite the proven therapeutic efficacy, resistance to the drug and reoccurrence of tumor appears to be a complication that many patients deal with. Molecular pathways underlying the development of resistance are being widely studied. METHODS AND RESULTS: In this study, using four established endocrine resistant breast cancer (ERBC) cell lines, we characterized CXCL1 as a secreted factor in crosstalk between ERBC cells and fibroblasts. Protein array revealed upregulation of CXCL1 and we confirmed the CXCL1 expression by real-time qRT-PCR and U-Plex assay. Co-culturing ERBC cells with fibroblasts enhanced the cell growth and migration compared to monoculture. The crosstalk of ERBC cells with fibroblasts significantly activates ERK/MAPK signaling pathway while reparixin, CXCR1/2 receptor inhibitor, attenuates the activity. Reparixin displayed the ERBC cell growth inhibition and the combination treatment with reparixin and CDK4/6 inhibitor (palbociclib and ribociclib) increased these inhibitory effect. CONCLUSIONS: Taken together, our study implicates CXCL1 as a critical role in ERBC growth and metastasis via crosstalk with fibroblast and cotargeting CXCR1/2 and CDK4/6 could potentially overcome endocrine resistant breast cancer.

Arctiin Inhibits Inflammation, Fibrosis, and Tumor Cell Migration in Rats With Ehrlich Solid Carcinoma.

BACKGROUND AND OBJECTIVES: ESC or Ehrlich solid carcinoma is a type of tumor originating from a spontaneous mammary adenocarcinoma in mice. It is a highly aggressive and fast-growing carcinoma that can create a solid mass when inserted under the skin. Its solid, undifferentiated form makes it an ideal model for researching cancer biology, tumor immunology, and testing various anti-cancer treatments. Additionally, arctiin has multiple beneficial properties, such as anti-proliferative, anti-oxidative, anti-adipogenic, and anti-bacterial. This study aimed to explore the potential anti-cancer benefits of arctiin in rats with ESC while also analyzing its effects on cell fibrosis markers, tumor cell migration, and inflammasome pathways. METHODS: Rats were given a tumor in their left hind limb via an intramuscular injection consisting of 2×106 cells. After eight days, some of the rats received a daily oral dose of 30 mg/kg of arctiin for three weeks. Muscle samples were observed under an electron microscope or stained with hematoxylin/eosin. Additionally, gene expression and protein levels of toll-like receptor 4 (TLR4), NLR family pyrin domain containing 3 (NLRP3), signal transducer and activator of transcription 3 (STAT3), transforming growth factor (TGF)-ß, endothelial growth factor (VEGF), and cyclin D1 were assessed in another part of the muscle samples. RESULTS: When ESC rats were given arctiin as a treatment, their mean survival time increased and their tumor volume and weight decreased. Additionally, when tumor tissue was examined under an electron microscope, it showed signs of pleomorphic cells, necrosis, nuclear fragmentation, membrane damage with cytoplasmic content spilling, and loss of cellular junction. The stained sections with hematoxylin/eosin showed a dense cellular mass and compressed, degenerated, and atrophied muscle. However, treatment with arctiin improved all these effects. Finally, the expression of TLR4, NLRP3, STAT3, TGF-ß, VEGF, and cyclin D1 was significantly reduced with arctiin treatment. CONCLUSIONS: Through the use of arctiin, tumor size and weight were effectively reduced, leading to an increase in the average survival time of rats and an improvement in muscle structure. Additional research has shown that arctiin is able to suppress inflammation, fibrosis, and the migration of tumor cells by inhibiting STAT3, TGF-ß1, TLR4, NLRP3, VEGF, and cyclin D1.

Profiles of COVID-19 vaccine hesitancy by race and ethnicity in eastern Pennsylvania.

BACKGROUND: Throughout US history, chronic and infectious diseases have severely impacted minority communities due to a lack of accessibility to quality healthcare and accurate information, as well as underlying racism. These fault lines in the care of minority communities in the US have been further exacerbated by the rise of the COVID-19 pandemic. This study examined the factors associated with COVID-19 vaccine hesitancy by race and ethnicity, particularly among African American and Latinx communities in Eastern Pennsylvania (PA). METHODS: Survey data was collected in July 2021 in Philadelphia, Scranton, Wilkes-Barre, and Hazleton, PA. The 203 participants (38.7% Black, 27.5% Latinx) completed the 28-question survey of COVID-19 vaccination attitudes in either English or Spanish. RESULT: Out of the 203 participants, 181 participants met all the inclusion criteria, including completed surveys; of these participants, over three-fifths (63.5%) were acceptant of the COVID-19 vaccine whereas the remainder (36.5%) were hesitant. Binary logistic regression results showed that age, concern for vaccine efficacy, race, knowledge on the vaccine, and belief that the COVID-19 virus is serious significantly influenced COVID-19 vaccine hesitancy. Minorities were more likely to be hesitant toward vaccination (OR: 2.8, 95% CI: 1.1, 6.8) than non-Hispanic whites. Those who believed the COVID-19 vaccine was ineffective (OR: 8.3, 95% CI: 3.8, 18.2), and that the virus is not serious (OR: 8.3, 95% CI: 1.1, 61.8) showed the greatest odds of hesitancy. CONCLUSIONS: Minority status, age less than 45 years, misinformation about seriousness of COVID-19 illness, and concern about vaccine efficacy were contributing factors of COVID-19 vaccine hesitancy. Therefore, understanding and addressing the barriers to COVID-19 vaccination in minority groups is essential to decreasing transmission and controlling this pandemic, and will provide lessons on how to implement public health measures in future pandemics.

The Awareness of Sudden Infant Death Among Saudi Arabian Women in 2023.

Background Sudden infant death syndrome (SIDS) refers to the unexpected and unexplained death of a child under one year old. The pathogenesis of SIDS remains unclear. However, certain factors such as the child's sleeping position, sleeping on a soft mattress, and maternal smoking have been suggested to contribute to its occurrence. The objective of this study was to evaluate the level of awareness of SIDS among Saudi Arabian women in 2023. Methodology A cross-sectional study was conducted among 300 mothers in Saudi Arabia, over a period of three months, from June to August 2023, using an online questionnaire to gather socio-demographic information from mothers of infants younger than one year old in Saudi Arabia, the sleeping practices of their infants, and their knowledge about SIDS risk factors. Data were coded using the Statistical Package for Social Sciences (SPSS) (IBM SPSS Statistics, Armonk, NY), and statistical significance tests were employed for data analysis. A p-value of <0.05 was considered significant. Results Among the 277 participating mothers, 44% were 31-40 years old, 93% were Saudi, 60% were employed, 65% were nonsmokers, and 64% placed babies in a supine position for sleep. About 37% of mothers used a duvet for bedding during summer, compared to 66% who used a duvet during winter, and 81% utilized a soft mattress cover in their children's beds. Additionally, 67% of mothers reported that their children used a pacifier while sleeping. More than half (54%) of mothers were aware of SIDS with media as their primary source of information. Among those under 21 years old, 50% demonstrated a high level of awareness, compared to 36% of those aged over 50. Conclusion Most women in this study were found to be unaware of SIDS. Among those who were aware, the media was the primary source of information. Higher educational attainment was associated with better understanding.

Prevalence of Low Back Pain Among University Attendants in Tabuk City During 2023: A Cross-Sectional Study in Saudi Arabia.

BACKGROUND: College students are at a higher risk of suffering low back pain (LBP). Assessing the magnitude of the problem and the associated risk factors can help reduce the suffering and disability in future doctors. AIM: This study was conducted to investigate the prevalence and related factors of LBP among medical students in the University of Tabuk and emphasize the need for targeted interventions that could help alleviate the burden of LBP among the students and improve their quality of life. METHODS: This cross-sectional study used an online well-structured, self-report questionnaire to collect the respondents' data. The questionnaire explored the participants' sociodemographic factors, lifestyle, and the severity of LBP-related disability using the modified Oswestry Low Back Pain Disability Questionnaire (Oswestry Disability Index (ODI)) score. RESULTS: The prevalence rate of LBP was 26.8%. The independent factors that significantly increased the probability of LBP included overweight/obesity (odds ratio (OR): 1.696, 95% confidence interval (CI): 1.086 to 2.648, p = 0.020) and stretching exercises (OR: 1.784, 95% CI: 1.104 to 2.883, p = 0.018). The independent predictors that significantly increased the severity of ODI included married marital status (p = 0.007), back surgery (p = 0.031), and higher pain intensity (p < 0.001). CONCLUSIONS: We found that the prevalence rate of LBP among our sample was around 26%. This rate is approximate to the rates reported in previous studies. Furthermore, the activities most affected by LBP were sitting, standing, and lifting. Future studies should explore other risk factors and attempt to determine the onset of pain. A longitudinal study design is recommended to identify the onset of developing LBP.

Assessing the Profile of Unvaccinated COVID-19 Individuals in African American and Latinx Communities in Eastern Pennsylvania

BackgroundThroughout US history, chronic and infectious diseases have severely impacted minority communities due to lack of accessibility to quality healthcare, accurate information, and underlying racism. These fault lines in the care of minority communities in the US have been further exposed by the rise of COVID-19 pandemic. This study examined the factors associated with COVID-19 vaccine hesitancy among African American and Latinx communities in Eastern Pennsylvania (PA). MethodsSurvey data was collected in July 2021 in Philadelphia, Scranton, Wilkes-Barre, and Hazleton, PA. The 203 participants (38.7% Black, 27.5% Latinx) completed the 28-question survey of COVID-19 vaccination attitudes in either English or Spanish. ResultsOut of a total of 181 participants that met inclusion criteria of completed surveys, results indicate that 63.5% (n=115) were acceptant of the COVID-19 vaccine whereas the remainder 36.5% (n=66) were hesitant. Binary logistic regression results showed that age, concern for vaccine efficacy, race, knowledge on the vaccine, and belief that the COVID-19 virus is serious significantly influenced COVID vaccine hesitancy. Minorities were more likely to be hesitant toward vaccination (OR: 2.77, 95% CI: 1.13, 6.79) than non-Hispanic whites. Those who believed the COVID vaccine was ineffective (OR: 8.29, 95% CI: 3.78,18.2), and that the virus is not serious (OR: 8.28, 95% CI: 1.11, 61.8) showed the greatest odds of hesitancy. ConclusionsContributing factors of vaccine hesitancy in minority communities were age, concern for vaccine efficacy, and education. Understanding and addressing the barriers to COVID-19 vaccination in minority groups is essential to decreasing transmission and controlling this pandemic.

Oncology Registered Dietitian Nutritionists' Knowledge, Attitudes, and Practices Related to Food Insecurity among Cancer Survivors: A Qualitative Study.

BACKGROUND: Understanding the knowledge, attitudes, and practices pertaining to food insecurity among oncology registered dietitian nutritionists (RDNs) is critical to ensuring that cancer survivors have adequate nutrition-a fundamental component of successful treatment and recovery. OBJECTIVE: To qualitatively assess oncology RDNs' knowledge, attitudes, and practices regarding the food access needs of their patients using a qualitative semantic approach to thematic analysis. DESIGN: The qualitative cross-sectional study was conducted from September 2018 to January 2019. PARTICIPANTS AND SETTING: Forty-one oncology RDNs working with cancer survivors in various clinical settings across the United States participated. MAIN OUTCOME MEASURES: Participants completed a semistructured, in-depth interview via telephone, lasting an average of 49 minutes. STATISTICAL ANALYSES PERFORMED: Two coders (primary and secondary) trained in qualitative thematic data analysis methods used a semantic approach to thematic analysis to analyze transcripts. A qualitative and mixed methods online coding program Dedoose was used to organize and analyze the data. RESULTS: Participants defined food insecurity (FI) as a lack of access to nutritious foods and a lack of resources to purchase nutritious foods. RDNs stated they believe FI is a serious problem in the United Staes, has a greater influence on cancer survivors than healthy individuals and they have specific concerns about FI among their own patients. Despite their concerns, most expressed that they do not use a validated tool to identify FI, nor were they aware that any exists. Only a small proportion of the RDNs stated that they regularly ask patients about their food access needs. CONCLUSIONS: Although Oncology RDNs have heard of FI, they do not routinely assess patients' food security status with a validated tool, nor do they consistently ask patients directly about their food access needs. These findings suggest there is a need for developing education and training opportunities for oncology RDNs to enhance their ability to screen for and address FI with their patients.

Carbohydrate Nutrition and the Risk of Cancer.

PURPOSE OF REVIEW: This review summarizes a selection of epidemiologic research assessing the associations between carbohydrate intake and cancer incidence and survival. Evidence for plausible biological mechanisms is also considered. RECENT FINDINGS: The mechanistic paradigm explaining the relationship between carbohydrates and cancer risk has been contested by numerous observational studies. Carbohydrates have conventionally been ascribed a deleterious role in the field of cancer research due to previous preclinical findings. A breadth of studies suggests that complex carbohydrate intake is inversely associated with risk of a number of cancer types. Data from studies assessing simple carbohydrates and cancer risk are mixed. Furthermore, recommendations for subsequent studies are framed.

A novel role for estrogen-induced signaling in the colorectal cancer gender bias.

Colorectal cancer (CRC) is a malignancy whose incidence is increasing globally, and there is a gender difference in the increasing risk. Evidence from hormone replacement therapy studies points to a role for circulating estrogens in suppressing the development of CRC. Estrogen receptor-ß has been identified as a tumor suppressor, but other actions of estrogen may also contribute to the difference in CRC incidence between men and women. The KCNQ1/KCNE3 potassium channel is regulated by estrogen in order to modulate chloride secretion during the menstrual cycle; the effect of estrogen on the colon is to promote fluid conservation during the implantation window. KCNQ1 is also a tumor suppressor in CRC, and its sustained expression has been linked to suppression of the Wnt/ß-catenin signaling pathway that contributes to CRC tumor progression. KCNQ1 regulation may represent a link between the normal physiological actions of estrogen in the colon and the hormone's apparent tumor-suppressive effects in CRC development.

The long-term effect of previous dental treatment under general anaesthesia on children's dental fear and anxiety.

BACKGROUND: Dental treatment under general anaesthesia (DGA) is deemed to contribute to children's dental fear and anxiety (DFA), both in the short term and long term. OBJECTIVE: To compare DFA between children who had previous DGA and those who did not. METHODS: A cross-sectional survey included 5- to 12-year-old children who had undergone DGA (n = 43) and a control group who had not (n = 55). Questionnaires were completed by parents regarding sociodemographic and dental profiles. Children's Fear Survey Schedule-Dental Subscale (CFSS-DS) and the Modified Child Dental Anxiety Scale (faces) (MCDASf) were completed by children. RESULTS: The mean age of the control group and the DGA group was 9.5 ± 1.7 and 8.8 ± 1.5 years old, respectively (P > 0.05). The time passed since DGA was experienced ranged between 1.2 and 6.9 years ago (mean: 4.2 ± 1.1 years). The mean CFSS-DS and MCDASf scores for the DGA group (34.3 and 20.4, respectively) were significantly greater when compared to the control group (23.6 and 12.7, respectively) (P < 0.001). CONCLUSION: Children who experienced DGA are a high-risk group for DFA several years after the procedure. The DGA status could be used for identifying anxious children to promote better behaviour management.

Detection of mutated Plasmodium vivax Kelch Propeller Domain (PvK12) in Malaysian isolates.

Malaysia is located near the borders of countries where artemisinin resistant Plasmodium falciparum (mutations in the P. falciparum Kelch propeller domain [PfK13]) have been reported. Plasmodium vivax Kelch propeller domain, PvK12, the ortholog of PfK13, could assess resistance towards artemisinin in vivax malaria. Polymorphisms in PvK12 gene were determined by PCR and sequencing was done in 300 clinical isolates collected in recent years (2012-2017) from hospitals within the country. Among 48 P. vivax samples, all were Sal-1 wild type alleles except for two isolates, a synonymous and nonsynonymous mutation respectively. The nonsynonymous (V552I) isolate was collected from an immigrant. P. vivax with mutated PvK12 is speculated to be an imported case and is likely to be circulating at very low frequency in Malaysia. An in-depth drug resistance surveillance among immigrants needs to be investigated to provide information that may be crucial for drug policy changes.

Multiple concurrent primary extramammary Paget's disease.

Extramammary Paget's disease (EMPD) is a rare malignant disorder of the skin, which was described in as early as the nineteenth century. EMPD usually occurs as a single lesion in the apocrine sweat gland-bearing skin with abundant hair follicles. Here, we present an elderly man who suffered from a non-resolving chronic genital pruritus for 8 months. Initially, he was managed for recurrent fungal infection and eczema. Later, a diagnosis of the rare condition multiple primary EMPD was made based on the histopathology findings and appropriate treatment was given.

Dirofilaria causing eye infection in a patient from Malaysia.

Human dirofilariasis caused by Dirofilaria immitis and Dirofilaria repens have been reported in Malaysia. This is the fourth reported case of dirofilariasis caused by D. repens. The patient was a Chinese male from Kuching Sarawak, Malaysia who presented with a one day history of redness and itchiness over the temporal aspect of his left eye. A worm was seen and later removed from beneath the conjunctiva under local anesthesia and based on the morphological characteristics, it was identified as an immature Dirofilaria repens.