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1.
Cell Biochem Funct ; 42(4): e4073, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38863227

ABSTRACT

Polycystic ovary syndrome (PCOS) is a multidisciplinary endocrinopathy that affects women of reproductive age. It is characterized by menstrual complications, hyperandrogenism, insulin resistance, and cardiovascular issues. The current research investigated the efficacy of rosmarinic acid in letrozole-induced PCOS in adult female rats as well as the potential underlying molecular mechanisms. Forty female rats were divided into the control group, the rosmarinic acid group (50 mg/kg per orally, po) for 21 days, PCOS group; PCOS was induced by administration of letrozole (1 mg/kg po) for 21 days, and rosmarinic acid-PCOS group, received rosmarinic acid after PCOS induction. PCOS resulted in a marked elevation in both serum luteinizing hormone (LH) and testosterone levels and LH/follicle-stimulating hormone ratio with a marked reduction in serum estradiol and progesterone levels. A marked rise in tumor necrosis factor-α (TNF-α), interleukin-1ß, monocyte chemotactic protein-1, and vascular endothelial growth factor (messenger RNA) in the ovarian tissue was reported. The histological analysis displayed multiple cystic follicles in the ovarian cortex with markedly thin granulosa cell layer, vacuolated granulosa and theca cell layers, and desquamated granulosa cells. Upregulation in the immune expression of TNF-α and caspase-3 was demonstrated in the ovarian cortex. Interestingly, rosmarinic acid ameliorated the biochemical and histopathological changes. In conclusion, rosmarinic acid ameliorates letrozole-induced PCOS through its anti-inflammatory and antiangiogenesis effects.


Subject(s)
Chemokine CCL2 , Cinnamates , Depsides , Disease Models, Animal , Letrozole , Polycystic Ovary Syndrome , Rosmarinic Acid , Vascular Endothelial Growth Factor A , Animals , Polycystic Ovary Syndrome/drug therapy , Polycystic Ovary Syndrome/chemically induced , Polycystic Ovary Syndrome/metabolism , Polycystic Ovary Syndrome/pathology , Female , Cinnamates/pharmacology , Depsides/pharmacology , Vascular Endothelial Growth Factor A/metabolism , Rats , Chemokine CCL2/metabolism , Letrozole/pharmacology , Luteinizing Hormone/blood , Luteinizing Hormone/metabolism , Immunohistochemistry , Testosterone/blood , Rats, Sprague-Dawley
2.
Iran J Pathol ; 19(1): 10-21, 2024.
Article in English | MEDLINE | ID: mdl-38864083

ABSTRACT

Background & Objective: Cervical cancer spreads to the pelvic lymph nodes, leading to a high incidence of cancer recurrence and unfavorable survival rates. Therefore, there is an urgent need to detect new predictive biomarkers for the early assessment of pelvic lymph node status in patients with cervical cancer. The current study aimed to assess the expression of FABP4, GINS2, and CBX7 in cervical cancer tissue to detect their prognostic and predictive roles in developing lymph node metastases in patients with that cancer type. Methods: We collected the tissues from patients with cervical cancer and evaluated the expression of FABP4, GINS2, and CBX7 using immunohistochemistry. We evaluated the association between their expression and clinicopathological and prognostic parameters. Results: A high expression of FABP4 and GINS2 and a low expression of CBX7 were found to be positively associated with the old age group, large tumor size, high grade and lymphovascular involvement, para-uterine organ infiltration, advanced FIGO stage, chemotherapeutic resistance, and tumor recurrence. Conclusion: We demonstrated the oncogenic roles of FABP4 and GISN2 in addition to the on-co-suppressive roles of CBX7 in cervical cancer and their association with poor clinicopathological criteria and poor survival. Our results may indicate that FABP4, GISN2, and CBX7 could be considered predictive biomarkers of the occurrence of lymph node metastases in the cancer of the cervix preoperatively, which could be beneficial in the accurate preoperative design therapy.

4.
Iran J Med Sci ; 49(1): 46-56, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38322160

ABSTRACT

Background: Letrozole, an aromatase inhibitor, has recently been introduced as the preferred treatment option for ectopic pregnancy. To date, no study has investigated the effect of letrozole alone on placental tissue. The present study aimed to evaluate the effect of different doses of letrozole on the placenta of rats and to clarify the underlying mechanism. Methods: Sixty pregnant female rats were equally divided into three groups, namely the control group (GI), low-dose (0.5 mg/Kg/day) letrozole group (GII), which is equivalent to the human daily dose (HED) of 5 mg, and high-dose (1 mg/Kg/day) letrozole group (GIII), equivalent to the HED of 10 mg. Letrozole was administered by oral gavage daily from day 6 to 16 of gestation. Data were analyzed using a one-way analysis of variance followed by Tukey's post hoc test and Chi square test. P<0.05 was considered statistically significant. Results: Compared to the GI and GII groups, high-dose letrozole significantly increased embryonic mortality with a high post-implantation loss rate (P<0.001) and significantly reduced the number of viable fetuses (P<0.001) and placental weight (P<0.001) of pregnant rats. Moreover, it significantly reduced placental estrogen receptor (ER) and progesterone receptor (PR) (P<0.001) and the expression of vascular endothelial growth factor (P<0.001), while increasing the apoptotic index of cleaved caspase-3 (P<0.001). Conclusion: Letrozole inhibited the expression of ER and PR in rat placenta. It interrupted stimulatory vascular signals causing significant apoptosis and placental vascular dysfunction. Letrozole in an equivalent human daily dose of 10 mg caused a high post-implantation loss rate without imposing severe side effects.


Subject(s)
Aromatase Inhibitors , Letrozole , Placenta , Animals , Female , Pregnancy , Rats , Aromatase Inhibitors/pharmacology , Letrozole/pharmacology , Placenta/drug effects , Receptors, Estrogen , Vascular Endothelial Growth Factor A
5.
Article in English | MEDLINE | ID: mdl-38358296

ABSTRACT

OBJECTIVE: To investigate the anogenital distance from the upper verge of the anus to the posterior fourchette (AGDAF ), FASL, and BCL2 combination as a reliable and non-invasive tool for the diagnosis of endometriosis. METHODS: This study included 100 women with endometriosis and 50 women without endometriosis as the control group. All cases underwent history taking, body mass index (BMI) measurement, AGD measurement, and FASL and BCL2 immunohistochemical staining of the eutopic endometrial tissue. RESULTS: This study included 150 women divided into endometriosis and control groups. Endometriosis cases significantly had shorter AGDAF , 22.9 ± 2.6 mm, compared with the control group, 27.3 ± 3.5 mm (P < 0.001). Lower FASL and higher BCL2 expression were associated with endometriosis (P < 0.001). The combined measurement of AGDAF (cut-off point 24.55 mm) with FASL and BCL2 was associated with endometriosis (P < 0.001). The combined diagnostic sensitivity, specificity, positive predictive value, and negative predictive value of AGDAF , FASL, and BCL2 were 83%, 78%, 87.3%, and 69.6%, respectively. The area under the curve was greater for AGDAF , FASL, and BCL2 in combination than for individual measurements. CONCLUSION: Combining short AGDAF with high BCL2 and low FASL is a highly sensitive, non-invasive diagnostic tool for endometriosis.

6.
J Lesbian Stud ; 28(1): 24-43, 2024.
Article in English | MEDLINE | ID: mdl-37679960

ABSTRACT

In this article, I examine lesbians' solidarity with trans people in the United States. Trans exclusionary radical feminists (TERFs) are feminists who believe that there is a stark difference between the biological reality of sex and the socially constructed nature of gender. They argue that sex is essential and innate. This leads some feminists to the argument that trans people are trying to infiltrate sex exclusive spaces. While TERFs are not always lesbians, lesbians are assumed to make up a large proportion of TERFs. As Thomsen and Essig argue that current ideologies within the media are allowing for the slippage between the terms "lesbian," "feminist," and "TERFs." Some scholars are suggesting that equating lesbian identities with transphobia and trans exclusion is but a new form of lesbian marginalization. I utilize 49 in-depth, qualitative interviews with lesbians across the United States to interrogate the stereotype that lesbians are largely TERFs. Through the voices of lesbians across the United States, I illustrate how many lesbians despise TERF ideology and argue that lesbians must stand in solidarity with trans people in the fight for social justice.


Subject(s)
Homosexuality, Female , Sexual and Gender Minorities , Female , Humans , United States , Feminism , Gender Identity , Stereotyping
7.
Nanoscale ; 15(36): 14782-14789, 2023 Sep 21.
Article in English | MEDLINE | ID: mdl-37548923

ABSTRACT

Exchange coupling in a model core-shell system is demonstrated as a step on the path to 3d exchange spring magnets. Employing a model system of Ni@CoFe2O4, high quality core-shell nanoparticles were fabricated using a simple two-step method. The microstructural quality was validated using TEM, confirming a well-defined interface between the core and the shell. A strongly temperature dependent two-phase magnetic hysteresis loop was measured, wherein an analysis of step heights indicates coupling of roughly 50% between the core and the shell. Element-specific XMCD hysteresis confirms the presence of exchange coupling, suppressing the superparamagnetism of the Ni core at room temperature, and reaching a coercivity of >6 kOe at 80 K. These results provide a pathway to the development of heterostructured metal-oxide exchange coupled nanoparticles with improved maximum energy product.

8.
Phys Rev Lett ; 131(4): 041002, 2023 Jul 28.
Article in English | MEDLINE | ID: mdl-37566836

ABSTRACT

The LUX-ZEPLIN experiment is a dark matter detector centered on a dual-phase xenon time projection chamber operating at the Sanford Underground Research Facility in Lead, South Dakota, USA. This Letter reports results from LUX-ZEPLIN's first search for weakly interacting massive particles (WIMPs) with an exposure of 60 live days using a fiducial mass of 5.5 t. A profile-likelihood ratio analysis shows the data to be consistent with a background-only hypothesis, setting new limits on spin-independent WIMP-nucleon, spin-dependent WIMP-neutron, and spin-dependent WIMP-proton cross sections for WIMP masses above 9 GeV/c^{2}. The most stringent limit is set for spin-independent scattering at 36 GeV/c^{2}, rejecting cross sections above 9.2×10^{-48} cm at the 90% confidence level.

9.
Rev Sci Instrum ; 94(3): 033102, 2023 Mar 01.
Article in English | MEDLINE | ID: mdl-37012755

ABSTRACT

This paper reports on a surface impedance measurement of a bulk metal niobium-titanium superconducting radio frequency (SRF) cavity in a magnetic field (up to 10 T). A novel method is employed to decompose the surface resistance contributions of the cylindrical cavity end caps and walls using measurements from multiple TM cavity modes. The results confirm that quality factor degradation of a NbTi SRF cavity in a high magnetic field is primarily from surfaces perpendicular to the field (the cavity end caps), while parallel surface resistances (the walls) remain relatively constant. This result is encouraging for applications needing high Q cavities in strong magnetic fields, such as the Axion Dark Matter eXperiment because it opens the possibility of hybrid SRF cavity construction to replace conventional copper cavities.

10.
Tijdschr Psychiatr ; 65(3): 202-204, 2023.
Article in Dutch | MEDLINE | ID: mdl-36951780

ABSTRACT

BACKGROUND: Hearing loss means a reduced access to a spoken language, depending on the severity and the possibility of hearing support. A sign language is on the other hand fully accessible. AIM: To describe the impact of hearing loss on mental health related to language ability. METHOD: From the literature a general picture will be presented of the impact of hearing loss on mental health. This is followed by a discussion of the influence of hearing loss on the prevalence and influence of diverse psychiatric conditions (schizophrenia, autism, depression/anxiety disorders). RESULTS: A relationship between mental health problems and hearing loss is evidenced. The use of a sign language seems to reduce the risk of a mental health problem in deaf individuals. CONCLUSION: The results have to be interpreted alongside the fact that research is based on relatively few countries. It is therefore not possible to generalize the results; cultural differences possibly exist. The relationship between language choice and language ability has not been studied in enough depth. More research and comparative research across countries is essential with full information on language choice/language ability.


Subject(s)
Deafness , Hearing Loss , Schizophrenia , Humans , Hearing Loss/epidemiology , Language , Sign Language
11.
Sci Rep ; 13(1): 3366, 2023 02 27.
Article in English | MEDLINE | ID: mdl-36849509

ABSTRACT

Manganese-enhanced magnetic resonance imaging can provide a surrogate measure of myocardial calcium handling. Its repeatability and reproducibility are currently unknown. Sixty-eight participants: 20 healthy volunteers, 20 with acute myocardial infarction, 18 with hypertrophic and 10 with non-ischemic dilated cardiomyopathy underwent manganese-enhanced magnetic resonance imaging. Ten healthy volunteers were re-scanned at 3 months. Native T1 values and myocardial manganese uptake were assessed for intra and inter-observer repeatability. Scan-rescan reproducibility was assessed in ten healthy volunteers. Intra-observer and inter-observer correlation was excellent in healthy volunteers for mean native T1 mapping [Lin's correlation coefficient (LCC) 0.97 and 0.97 respectively] and myocardial manganese uptake (LCC: 0.99 and 0.96 respectively). Scan-rescan correlation for native T1 and myocardial manganese uptake was also excellent. Similarly, intra-observer correlations for native T1 and myocardial manganese uptake in patients with acute myocardial infarction (LCC: 0.97 and 0.97 respectively), hypertrophic (LCC: 0.98 and 0.97 respectively) and dilated cardiomyopathy (LCC: 0.99 and 0.95 respectively) were excellent. Limits of agreement were broader in patients with dilated cardiomyopathy. Manganese-enhanced magnetic resonance imaging has high repeatability and reproducibility in healthy myocardium and high repeatability in diseased myocardium. However, further study is needed to establish robustness in pathologies with diffuse myocardial fibrosis.


Subject(s)
Breast Neoplasms , Cardiomyopathy, Dilated , Myocardial Infarction , Precancerous Conditions , Humans , Female , Manganese , Cardiomyopathy, Dilated/diagnostic imaging , Reproducibility of Results , Myocardial Infarction/diagnostic imaging , Hypertrophy , Magnetic Resonance Imaging
12.
Am J Physiol Heart Circ Physiol ; 324(3): H293-H304, 2023 03 01.
Article in English | MEDLINE | ID: mdl-36637971

ABSTRACT

Chronic stimulation of cardiac α1A-adrenergic receptors (α1A-ARs) improves symptoms in multiple preclinical models of heart failure. However, the translational significance remains unclear. Human engineered heart tissues (EHTs) provide a means of quantifying the effects of chronic α1A-AR stimulation on human cardiomyocyte physiology. EHTs were created from thin slices of decellularized pig myocardium seeded with human induced pluripotent stem cell (iPSC)-derived cardiomyocytes and fibroblasts. With a paired experimental design, EHTs were cultured for 3 wk, mechanically tested, cultured again for 2 wk with α1A-AR agonist A61603 (10 nM) or vehicle control, and retested after drug washout for 24 h. Separate control experiments determined the effects of EHT age (3-5 wk) or repeat mechanical testing. We found that chronic A61603 treatment caused a 25% increase of length-dependent activation (LDA) of contraction compared with vehicle treatment (n = 7/group, P = 0.035). EHT force was not increased after chronic A61603 treatment. However, after vehicle treatment, EHT force was increased by 35% relative to baseline testing (n = 7/group, P = 0.022), suggesting EHT maturation. Control experiments suggested that increased EHT force resulted from repeat mechanical testing, not from EHT aging. RNA-seq analysis confirmed that the α1A-AR is expressed in human EHTs and found chronic A61603 treatment affected gene expression in biological pathways known to be activated by α1A-ARs, including the MAP kinase signaling pathway. In conclusion, increased LDA in human EHT after chronic A61603 treatment raises the possibility that chronic stimulation of the α1A-AR might be beneficial for increasing LDA in human myocardium and might be beneficial for treating human heart failure by restoring LDA.NEW & NOTEWORTHY Chronic stimulation of α1A-adrenergic receptors (α1A-ARs) is known to mediate therapeutic effects in animal heart failure models. To investigate the effects of chronic α1A-AR stimulation in human cardiomyocytes, we tested engineered heart tissue (EHT) created with iPSC-derived cardiomyocytes. RNA-seq analysis confirmed human EHT expressed α1A-ARs. Chronic (2 wk) α1A-AR stimulation with A61603 (10 nM) increased length-dependent activation (LDA) of contraction. Chronic α1A-AR stimulation might be beneficial for treating human heart failure by restoring LDA.


Subject(s)
Heart Failure , Induced Pluripotent Stem Cells , Humans , Animals , Swine , Adrenergic Agonists/metabolism , Adrenergic Agonists/pharmacology , Adrenergic Agonists/therapeutic use , Myocardial Contraction , Induced Pluripotent Stem Cells/metabolism , Heart Failure/drug therapy , Heart Failure/metabolism , Myocytes, Cardiac/metabolism , Receptors, Adrenergic/metabolism , Receptors, Adrenergic/therapeutic use , Receptors, Adrenergic, alpha-1/metabolism
13.
LGBT Health ; 10(3): 237-244, 2023 04.
Article in English | MEDLINE | ID: mdl-36579918

ABSTRACT

Purpose: Lesbian, gay, bisexual, transgender, queer, and other sexual and gender minority (LGBTQ+) people face mental health disparities. These disparities are amplified in the Southern regions of the United States. This study assessed the role of outness, discrimination, and other demographic variables on possible serious mental illness (SMI) among LGBTQ+ Southerners. Methods: This study used data from the 2017 LGBT Institute Southern Survey, a cross-sectional convenience sample of 6502 LGBTQ+ adults living in 14 Southern states. Multivariable logistic regression was performed to examine differences between those with and without possible SMI. Results: Outness was associated with a lower likelihood of possible SMI (odds ratio [OR]: 0.696, 95% confidence interval [CI]: 0.574-0.844, p = 0.001), especially when controlling for discrimination in the past 12 months (OR: 0.693, 95% CI: 0.576-0.834, p ≤ 0.001) and lifetime discrimination (OR: 0.678, 95% CI: 0.554-0.829, p = 0.001). Lifetime discrimination was associated with a higher likelihood of possible SMI (OR: 1.413, 95% CI: 1.034-1.932, p = 0.033), as was discrimination experienced in the past 12 months (OR: 1.626, 95% CI: 1.408-1.877, p ≤ 0.001). Black/African American respondents had the lowest percentage of possible SMI (21.0%) compared with other races, despite having lower or comparable rates of outness. Conclusion: These results indicate a possible promotive effect of outness against possible SMI among LGBTQ+ Southerners, as well as possible promotive group-level factors among Black/African American LGBTQ+ Southerners. Policies and interventions that address discrimination against LGBTQ+ Southerners should be expanded, and future research should address how the relationships between outness, discrimination, and mental health outcomes may vary by subgroup.


Subject(s)
Homosexuality, Female , Psychological Distress , Sexual and Gender Minorities , Adult , Female , Humans , United States , Cross-Sectional Studies , Homosexuality, Female/psychology , Bisexuality/psychology
14.
Benef Microbes ; 14(6): 525-551, 2023 Nov 27.
Article in English | MEDLINE | ID: mdl-38350464

ABSTRACT

Bifidobacterium adolescentis is one of the most abundant bifidobacterial species in the human large intestine, and is prevalent in 60-80% of healthy human adults with cell densities ranging from 109-1010 cells/g of faeces. Lower abundance is found in children and in elderly individuals. The species is evolutionary adapted to fermenting plant-derived glycans and is equipped with an extensive sugar transporter and degradation enzymes repertoire. Consequently, the species is strongly affected by dietary carbohydrates and is able to utilize a wide range of prebiotic molecules. B. adolescentis is specialized in metabolizing resistant starch and is considered a primary starch degrader enabling growth of other beneficial bacteria by cross-feeding. The major metabolic output is acetate and lactate in a ratio of 3:2. Several health-beneficial properties have been demonstrated in certain strains of B. adolescentis in vitro and in rodent models, including enhancement of the intestinal barrier function, anti-inflammatory and immune-regulatory effects, and the production of neurotransmitters (GABA), and vitamins. Although causalities have not been established, reduced abundance of B. adolescentis as part of a dysbiotic colonic microbiota in human observational studies has been associated with inflammatory bowel diseases, irritable bowel syndrome, coeliac disease, cystic fibrosis, Helicobacter pylori infection, type 1 and 2 diabetes, metabolic syndrome, nonalcoholic steatohepatitis, and certain allergies. It is therefore reasonable to conceive B. adolescentis as a health-associated, or even health-promoting bacterial species in humans.


Subject(s)
Bifidobacterium adolescentis , Diabetes Mellitus, Type 1 , Diabetes Mellitus, Type 2 , Helicobacter Infections , Helicobacter pylori , Probiotics , Adult , Child , Humans , Aged , Probiotics/metabolism
15.
Oxid Med Cell Longev ; 2022: 5260085, 2022.
Article in English | MEDLINE | ID: mdl-36132229

ABSTRACT

Pregnancy-related cardiovascular disease with stroke remains a considerable source of higher maternal morbidity and mortality occurs in periods of pregnancy, delivery, and postpartum. It is essential to counsel the mother before pregnancy by an expert cardiologist and obstetric team to discuss any event related to preexistent cardiac or past preeclampsia for estimation of maternal and fetal risks. In pregnancy, the cardiac state includes hypertensive disorders, ischemic heart disease, valvular disease, and postpartum stroke. The incidence of stroke is increasing in pregnancy, particularly in postpartum, and its strong relationship with hypertensive disorders of pregnancy (preeclampsia). The combined cardiologist and obstetrics team requires during pregnancy mainly due to the approach to the management of a cardiac disease that subsequently prevents stroke postpartum. Therefore, a general perception of cardiac disease during pregnancy, delivery, and postpartum should be a core knowledge extent for all cardiovascular and clinicians. Many studies provided linked that deregulation of microRNAs (miRNAs) in maternal circulation and placenta tissue may development of pregnancy complications including preeclampsia considered a diagnostic marker. The desire of this review provides a detailed outline of current knowledge and dealing in this field with strength on the physiological changes during pregnancy.


Subject(s)
Heart Diseases , Hypertension , MicroRNAs , Pre-Eclampsia , Pregnancy Complications , Stroke , Female , Heart Diseases/complications , Heart Diseases/genetics , Humans , Hypertension/complications , MicroRNAs/genetics , Pre-Eclampsia/genetics , Pregnancy , Stroke/etiology
16.
PLoS One ; 17(7): e0271625, 2022.
Article in English | MEDLINE | ID: mdl-35857813

ABSTRACT

AIMS: This study surveyed people regarding their acceptance of periodic doses (i.e., annual boosters) of the COVID-19 vaccine. Moreover, factors that correlate with attitudes toward periodic COVID-19 vaccines were assessed and identified. METHOD: The study employed a cross-sectional methodology. The study questionnaire was distributed using Google Forms. Data were collected during the last quarter of 2021, and 1,416 adults (18 years old and over) from Jordan responded. Acceptance of COVID-19 periodic vaccine doses was calculated as a percentage of the total number of study participants, and their attitudes were scored. A multiple regression model was used to determine the predictors of public attitudes toward the annual dose of COVID-19 vaccines. RESULTS: The acceptance rate for receiving periodic doses of the COVID-19 vaccine was low (19.3%). Additionally, 26% of participants were unsure about receiving additional doses of the vaccine. However, 54.7% had a negative attitude toward getting periodic doses. The mean score for attitudes toward periodic doses was 47.9 (range: 29-66). Among the identified factors leading to decisions not to receive periodic doses were side effects (49.1%), waiting for further clinical studies (38.8%), and perceived no risk of contracting COVID-19 (17.7%). Regression analysis showed that income, educational attainment, and following the news about COVID-19 were predictors of participants' attitudes toward the periodic COVID-19 vaccine. CONCLUSION: Acceptance of periodic doses of the COVID-19 vaccine in Jordan is low, and the public's attitude is generally negative. Health programs and educational interventions are needed to promote vaccine acceptance and positive attitudes.


Subject(s)
COVID-19 Vaccines , COVID-19 , Adolescent , Adult , Attitude , COVID-19/epidemiology , COVID-19/prevention & control , Cross-Sectional Studies , Health Knowledge, Attitudes, Practice , Humans , Jordan , Surveys and Questionnaires , Vaccination
17.
Tech Coloproctol ; 26(5): 363-372, 2022 05.
Article in English | MEDLINE | ID: mdl-35084620

ABSTRACT

BACKGROUND: The purpose of this study was to investigate associations between mode of presentation; categorized as emergency, suspected cancer outpatient referral pathway (2-week wait or 2WW pathway), non-cancer suspected outpatient referral (non-2-week wait pathway) or following screening, and stage of diagnosis and survival in patients with colorectal cancer in England. METHODS: This was a retrospective cohort observational study of patients diagnosed with colorectal cancer between January 2010 and December 2014 in England using data from Public Health England collated from regional cancer registries. RESULTS: The most common route to diagnosis among 167,501 patients diagnosed with colorectal cancer was via the non-cancer suspect (non-2WW) outpatient referral pathway (35.1%) followed by the suspected cancer (2WW) referral pathway (31.6%), emergency presentation (22.8%) and most infrequently following screening (10.6%) (p < 0.01). Screening confers the greatest likelihood of early-stage diagnosis (61.6%) compared to other modes of presentation. The 5-year overall survival was 81.8%, 53.3%, 53.0% and 27.6% in those diagnosed via screening, 2WW, non-2WW pathway and emergency presentation, respectively. Patients from most deprived regions were more likely to be diagnosed following emergency presentation (27.7 vs 19.7%, p < 0.01) and less likely via screening (8.1 vs 12%, p < 0.01). CONCLUSIONS: Asymptomatic individuals diagnosed following screening have earlier stage cancers and better survival, the opposite was observed in those diagnosed following emergency presentation. Patients referred via the 2WW pathway do not have better survival outcomes when compared to those referred via the non-2WW pathway. In addition, this study has identified socio-economic groups that need to be targeted with public health campaigns to improve screening uptake.


Subject(s)
Colorectal Neoplasms , Referral and Consultation , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/epidemiology , England/epidemiology , Humans , Retrospective Studies
18.
Ir J Psychol Med ; 39(4): 335-339, 2022 12.
Article in English | MEDLINE | ID: mdl-31543078

ABSTRACT

The psychedelic research renaissance is gaining traction. Preliminary clinical studies of the hallucinogenic fungi, psilocybin, with psychological support, have indicated improvements in mood, anxiety and quality of life. A seminal, open-label study demonstrated marked reductions in depression symptoms in participants with treatment-resistant depression (TRD). The associated neurobiological processes involve alterations in brain connectivity, together with altered amygdala and default mode network activity. At the cellular level, psychedelics promote synaptogenesis and neural plasticity. Prompted by the promising preliminary studies, a randomized, double-blind trial has recently been launched across Europe and North America to investigate the efficacy of psilocybin in TRD. One of these centres is based in Ireland - CHO Area 7 and Tallaght University Hospital. The outcome of this trial will determine whether psilocybin with psychological support will successfully translate into the psychiatric clinic for the benefit of patients.


Subject(s)
Hallucinogens , Psychiatry , Humans , Anxiety , Hallucinogens/therapeutic use , Psilocybin/therapeutic use , Quality of Life , Double-Blind Method
19.
Br J Oral Maxillofac Surg ; 59(10): 1275-1279, 2021 12.
Article in English | MEDLINE | ID: mdl-34483009

ABSTRACT

The recent eighth edition of the American Joint Committee on Cancer (AJCC) staging system has introduced depth of invasion (DOI) as one of its important components. DOI is also important for deciding neck management in superficial tongue cancers. Magnetic resonance imaging (MRI) is mainly used to assess DOI, and in this study we have evaluated the efficacy of MRI to detect it. This is a retrospective study consisting of 60 treatment-naïve tongue cancer patients operated on between July 2017 and June 2019. Patients underwent MR imaging on an Optima MR450W 1.5T unit, and MRI was reported by two experienced head and neck radiologists. Postoperative histological DOI was considered the gold standard. The correlation coefficient was derived for postoperative DOI and MRI-detected DOI. A subgroup analysis of superficial tongue cancer was also done. The mean MRI DOI was 13.7 mm and the mean histological DOI 12.45 mm. The shrinkage factor was 0.6 mm. Pearson's correlation coefficient was 0.80 (p=<0.001) for Radiologist 1 and 0.85 (p=<0.001) for Radiologist 2. The interobserver variation was low, with a correlation coefficient between the two radiologists of 0.965 (p=<0.001). For superficial tongue cancers there was moderate correlation for MRI and histologically-detected DOI with a kappa value of 0.681 (p=0.03). As per the ROC curve, the cut-off value for MRI DOI to predict nodal metastasis was 4.6 mm. MRI has high reliability to predict the DOI of tongue cancers. The interobserver variation was low. The diagnostic accuracy in cases of superficial tongue cancer was moderate.


Subject(s)
Carcinoma, Squamous Cell , Tongue Neoplasms , Humans , Magnetic Resonance Imaging , Neoplasm Invasiveness , Neoplasm Staging , Reproducibility of Results , Retrospective Studies
20.
Sci Rep ; 11(1): 13493, 2021 06 29.
Article in English | MEDLINE | ID: mdl-34188159

ABSTRACT

The rate of the remodeling of the arterialized saphenous vein conduit limits the outcomes of coronary artery bypass graft surgery (CABG), which may be influenced by endothelial dysfunction. We tested the hypothesis that high stretch (HS) induces human saphenous vein endothelial cell (hSVEC) dysfunction and examined candidate underlying mechanisms. Our results showed that in vitro HS reduces NO bioavailability, increases inflammatory adhesion molecule expression (E-selectin and VCAM1) and THP-1 cell adhesion. HS decreases F-actin in hSVECs, but not in human arterial endothelial cells, and is accompanied by G-actin and cofilin's nuclear shuttling and increased reactive oxidative species (ROS). Pre-treatment with the broad-acting antioxidant N-acetylcysteine (NAC) supported this observation and diminished stretch-induced actin remodeling and inflammatory adhesive molecule expression. Altogether, we provide evidence that increased oxidative stress and actin cytoskeleton remodeling play a role in HS-induced saphenous vein endothelial cell dysfunction, which may contribute to predisposing saphenous vein graft to failure.


Subject(s)
Actins/metabolism , Endothelial Cells/metabolism , Oxidative Stress , Saphenous Vein/metabolism , Stress, Mechanical , Humans , Reactive Oxygen Species/metabolism , THP-1 Cells
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