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Background: Cellular senescence can have positive and negative effects on the body, including aiding in damage repair and facilitating tumor growth. Adamantinomatous craniopharyngioma (ACP), the most common pediatric sellar/suprasellar brain tumor, poses significant treatment challenges. Recent studies suggest that senescent cells in ACP tumors may contribute to tumor growth and invasion by releasing a senesecence-associated secretory phenotype. However, a detailed analysis of these characteristics has yet to be completed., Methods: We analyzed primary tissue samples from ACP patients using single-cell, single-nuclei, and spatial RNA sequencing. We performed various analyses, including gene expression clustering, inferred senescence cells from gene expression, and conducted cytokine signaling inference. We utilized LASSO to select essential gene expression pathways associated with senescence. Finally, we validated our findings through immunostaining., Results: We observed significant diversity in gene expression and tissue structure. Key factors such as NFKB, RELA, and SP1 are essential in regulating gene expression, while senescence markers are present throughout the tissue. SPP1 is the most significant cytokine signaling network among ACP cells, while the Wnt signaling pathway predominantly occurs between epithelial and glial cells. Our research has identified links between senescence-associated features and pathways, such as PI3K/Akt/mTOR, MYC, FZD, and Hedgehog, with increased P53 expression associated with senescence in these cells., Conclusions: A complex interplay between cellular senescence, cytokine signaling, and gene expression pathways underlies ACP development. Further research is crucial to understand how these elements interact to create novel therapeutic approaches for patients with ACP., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

A recent article brought together the health benefits of unionization and working under collective agreements. It was noted how Canadian health promotion texts, reports and statements made no mention of unionization and working under collective agreements as promoting health. This was seen as a significant omission and reasons for this were considered. In this article this analysis is extended to consider how contributors to the flagship health promotion journal Health Promotion International (HPI) conceptualize unions, unionization and working under collective agreements as promoting health. Of 2443 articles published in HPI since its inception, 87 or 3.6% make mention of unions, unionization, collective agreements or collective bargaining, with most saying little about their promoting health. Instead, 20 make cursory references to unions or merely see them as providing support and engagement opportunities for individuals. Forty-five depict unions or union members as involved in a health promotion programme or activity carried out by the authors or by government agencies. Only 33 articles explicitly mention unions, unionization or collective agreements as potentially health promoting, representing 1.3% of total HPI content since 1986. We conclude that the health promoting possibilities of unionization and working under collective agreements is a neglected area amongst HPI contributors. Reasons for this are explored and an Organisation for Economic Cooperation and Development report on the importance of collective bargaining is drawn upon to identify areas for health promotion research and action., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aims: Mitral annular disjunction is fibrous separation between the attachment of the posterior mitral leaflet and the basal left ventricular myocardium initially described in dissected hearts. Currently, it is commonly evaluated by echocardiography, and potential relationships with mitral valve prolapse and ventricular arrhythmia have been suggested. However, controversy remains as its prevalence and extent have not been fully elucidated in normal living subjects., Methods and Results: Systolic datasets of cardiac computed tomography obtained from 98 patients (mean age, 69.1 ± 12.6 years; 81% men) with structurally normal hearts were assessed retrospectively. Circumferential extent of both mitral leaflets and disjunction was determined by rotating orthogonal multiplanar reconstruction images around the central axis of the mitral valvar orifice. Distribution angle within the circumference of the mitral valvar attachment and maximal height of disjunction were quantified. In total, 96.0% of patients demonstrated disjunction. Average distribution angles of the anterior and posterior mitral leaflets were 91.3 ± 9.4° and 269.8 ± 9.7°, respectively. Average distribution angle of the disjunction was 105.1 ± 49.2°, corresponding to 39.0 ± 18.2% of the entire posterior mitral valvar attachment. Median value of the maximal height of disjunction was 3.0 (1.5-7.0) mm. Distribution prevalence map of the disjunction revealed characteristic double peaks, with frequent sites of the disjunction located at the anterior to antero-lateral and inferior to infero-septal regions., Conclusion: Mitral annular disjunction is a rather common finding in the normal adult heart with bimodal distribution predominantly observed involving the P1 and P3 scallops of the posterior mitral leaflet., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

There is little doubt that the implementation of a Basic Income Guarantee (BIG) in Canada and other liberal welfare states would alleviate some of the most egregious examples of absolute poverty that contribute to poor health such as lack of adequate food and shelter and inability to meet basic household and personal needs. BIG would likely improve the health of the most disadvantaged by moving them closer to the relative poverty line. Yet, advocacy for and implementation of BIG carries potential dangers. Since health improves with every step up the income ladder, simply moving people closer to the relative poverty line without providing additional universal benefits and supports common to most other developed nations would limit its health promotion potential. In addition, governing authorities in liberal political economies can use BIG to justify continuing imbalances in economic and political power that skews the distribution of the social determinants of health. In addition, implementation of BIG -- despite its more progressive advocates calls for maintaining or enhancing of existing social programs - can serve as justification for reducing or removing these programs, thereby threatening health., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: We tested the hypothesis that a single high sensitivity troponin at limits of detection (LOD HSTnT) (<5 ng/l) combined with a presentation non-ischaemic electrocardiogram is superior to low-risk Global Registry of Acute Coronary Events (GRACE) (<75), Thrombolysis in Myocardial Infarction (TIMI) (≤1) and History, ECG, Age, Risk factors and Troponin (HEART) score (≤3) as an aid to early, safe discharge for suspected acute coronary syndrome., Methods: In a prospective cohort study, risk scores were computed in consecutive patients with suspected acute coronary syndrome presenting to the Emergency Room of a large English hospital. Adjudication of myocardial infarction, as per third universal definition, involved a two-physician, blinded, independent review of all biomarker positive chest pain re-presentations to any national hospital. The primary and secondary outcome was a composite of type 1 myocardial infarction, unplanned coronary revascularisation and all cause death (MACE) at six weeks and one year., Results: Of 3054 consecutive presentations with chest pain 1642 had suspected acute coronary syndrome (52% male, median age 59 years, 14% diabetic, 20% previous myocardial infarction). Median time from chest pain to presentation was 9.7 h. Re-presentations occurred in eight hospitals with 100% follow-up achieved. Two hundred and eleven (12.9%) and 279 (17%) were adjudicated to suffer MACE at six weeks and one year respectively. Only HEART ≤3 (negative predictive value MACE 99.4%, sensitivity 97.6%, %discharge 53.4) and LOD HSTnT strategy (negative predictive value MACE 99.8%, sensitivity 99.5%, %discharge 36.9) achieved pre-specified negative predictive value of >99% for MACE at six weeks. For type 1 myocardial infarction alone the negative predictive values at six weeks and one year were identical, for both HEART ≤3 and LOD HSTnT at 99.8% and 99.5% respectively., Conclusion: HEART ≤3 or LOD HSTnT strategy rules out short and medium term myocardial infarction with ≥99.5% certainty, and short-term MACE with >99% certainty, allowing for early discharge of 53.4% and 36.9% respectively of suspected acute coronary syndrome. Adoption of either strategy has the potential to greatly reduce Emergency Room pressures and minimise follow-up investigations. Very early presenters (<3 h), due to limited numbers, are excluded from these conclusions.

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are a major development in the prevention of cardiovascular disease (CVD) and is one of the most significant discoveries since the development of statin therapy. Administration of two human monoclonal antibodies to PCSK9 (alirocumab and evolocumab) can significantly reduce low-density lipoprotein cholesterol (LDL-c) concentrations, thus improving lipid management. Accordingly, guidelines on the specific indications for alirocumab and evolocumab usage have been released. This multicentre study aimed to estimate the proportion of patients treated for an acute myocardial infarction (MI) who could be considered for PCSK9 inhibitors under the current National Institute for Health and Care Excellence (NICE) lipid targets criteria., Methods: The records of 596 patients in two large hospitals in Liverpool, UK were analysed. Information was collected on lipid profiles during and after admission, lipid-lowering therapy and previous CVD., Results: At least 2.2% of patients were eligible for PCSK9 inhibitors post-MI under the current NICE guidance. Additionally, 29% of patients failed to achieve LDL-c concentrations <2.0 mmol/L despite maximum statin therapy and failed to meet eligibility for PCSK9 inhibitors as per the NICE criteria. This cohort represents a group of patients 'in limbo', in which statin therapy alone is not sufficient to reduce LDL-c., Conclusions: PCSK9 inhibitors are expensive and so their use must be highly selective. At present, in a real-world setting with ezetimibe underprescribing, ~2% of patients are eligible and a further 30% are deprived of benefit and improved outcomes by lack of optimisation and/or potential use of PCSK9 inhibitors., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Observation of the microvasculature using narrow band imaging (NBI) with magnifying endoscopy is useful for diagnosing superficial squamous cell carcinoma. Increased vascular density is indicative of cancer, but not many studies have reported differences between cancerous and noncancerous areas based on an objective comparison. We observed specimens of endoscopic submucosal dissection (ESD) using NBI magnification, and determined the vascular density of cancerous and noncancerous areas. A total of 25 lesions of esophageal squamous cell carcinoma that were dissected en bloc by ESD between July 2013 and December 2013 were subjected to NBI magnification. We constructed a device that holds an endoscope and precisely controls the movement along the vertical axis in order to observe submerged specimens by NBI magnification. NBI image files of both cancerous (pathologically determined invasion depth, m1/2) and surrounding noncancerous areas were created and subjected to vascular density assessment by two endoscopists who were blinded to clinical information. The invasion depth was m1/2 in 20, m3/sm1 in four and sm2 in one esophageal cancer lesion. Mean vascular density was significantly increased in cancerous areas (37.6 ± 16.3 vessels/mm2) compared with noncancerous areas (17.6 ± 10.0 vessels/mm2) (P < 0.05). The correlation coefficients between vascular density determined by two endoscopists were 0.86 and 0.81 in cancerous and noncancerous areas, respectively. Receiver operating curve (ROC) analysis revealed that the area under the curve (AUC) of vascular density was 0.895 (95% CI, 0.804-0.986). For this ROC curve, sensitivity was 78.3% and specificity was 87.0% when the cutoff value of vascular density was 26 vessels/mm2. NBI magnification confirmed significant increases in vascular density in cancerous areas compared with noncancerous areas in esophageal squamous cell carcinoma. The rates of agreement between vascular density values determined by two independent operators were high., (© The Authors 2017. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Small cell esophageal carcinoma(SCEC) is a rare disease with aggressive behavior and poor prognosis. Because of the rarity of this disease, standard therapy has not yet been established. The objective of this retrospective study was to report the outcomes of SCEC treated with chemotherapy and radiotherapy from a retrospective study of 11 patients. We enrolled 11 SCEC patients who were treated with radiation therapy (more than 50 Gy) and chemotherapy between May 1996 and October 2007. Patients' age ranged from 44 to 77 years (mean: 69 years). In all patients, pathological examination of the specimen obtained by biopsy revealed small cell carcinoma. All patients were treated with chemotherapy and radiation therapy. The mean follow-up time was 14.7 months, and the median overall survival time of all patients was 13.2 months (range: 4.2-43.6 months). The 1-year and 3-year overall survival rates were 63% and 24%, respectively, while the 1-year and 3-year progression-free survival rates were 45% and 14%, respectively. Five of seven patients with complete response (CR) developed recurrent disease. Recurrence sites were distant metastases in four patients and lymph node outside the radiation field in one patient. Chemoradiation should be considered as one of the important treatment options for the loco-regional control in the patients with SCEC.

Objective: To evaluate the outcome of radiotherapy for recurrent esophageal cancer after surgery and to determine the prognostic factors., Methods: From 1987 through 2002, 82 patients treated with radiotherapy for loco-regional recurrences of esophageal cancer after surgery were retrospectively reviewed. The stage at initial surgery was I in 16, II in 41, III or higher in 24 and unknown in 1. The median size of recurrent tumors was 3.5 cm in diameter. Fifty-two patients were treated with radiotherapy alone, and 30 were treated with radiotherapy combined with chemotherapy. The median total dose of external radiotherapy given was 50.4 Gy in 28 fractions., Results: The median survival period after recurrence was 7.0 months. The 2- and 5-year overall survival rate for all patients was 22 and 11%, respectively. In univariate analysis, the patients with performance status (PS) = 0-1, or tumor size <3.5 cm, and those treated with total dose >/=50 Gy showed a better survival outcome than each the other groups. The patients with a history of previous radiotherapy showed a poorer survival outcome in univariate analysis than each the other groups. In multivariate analysis, tumor size, PS and radiation dose were independent prognostic factors for overall survival., Conclusion: The prognosis of patients with post-operative loco-regional recurrence of esophageal cancer is poor. However, a long-term survival may be expected by definitive radiotherapy for the patients with small-size tumors and with a good PS.

Objective: To assess tongue atrophy and long-term functional outcome of mobile tongue cancer patients after interstitial radiotherapy., Methods: Of 493 patients whose squamous cell carcinoma of the mobile tongue had been treated with low dose rate brachytherapy, there were 57 patients evaluated between July 2002 and April 2004 whose tongue had not been modified by surgical procedures and who had no primary recurrence. The median time from treatment to evaluation was 96 months (range: 9-214 months). Almost all of the patients belonged to the early stage tongue cancer (T1/T2/T3/T4=30:24:3:0), and all had received interstitial radiotherapy with a single-plane implant. To evaluate the deformity of the tongue, we used a grading system that classified the atrophic changes of the tongue into four categories (G0-G3)., Results: Thirty-nine patients (70%) showed mild tongue hemiatrophy (G1 or G2) in the irradiated side. However, no patients showed severe atrophy where the tongue cannot be made to protrude beyond the incisors (G3). The length of time after brachytherapy was >72 months and the age of the patients at brachytherapy had the same statistical significance (P=0.0366). As for functional outcome, understandability of speech and a normal diet were preserved for almost all patients., Conclusion: The progression of atrophic change in the irradiated tongue occurred over a long term after brachytherapy. However, most patients could maintain their activities of daily life without severe restriction.

Population health as developed by the Canadian Institute for Advanced Research (CIAR) has influenced the shape and direction of Canadian public health policy, and has the potential to do so in the USA and elsewhere. There is reason to be concerned about this ascendence of CIAR thinking: population health is rooted within epidemiology, a militantly quantitative discipline; population health eschews analysis of societal structures as determinants of health; and population health elevates scientific understanding over health promotion action. Its lack of an explicit values base is also problematic. Policy makers should recognize these and other limitations as they consider models for a new public health.

A framework of policy development is presented that identifies the role various forms of knowledge can play in the policy formation process. The framework is based upon the premise that public health and health promotion issues should be addressed within an analysis of policy change that considers concepts of interactive and critical knowledge in addition to scientific knowledge. Progress in developing meaningful health policy will require accepting the validity of these various forms of knowledge and developing frameworks that see experts and citizens working together to develop and achieve public health and health promotion goals.

Aims: This study aimed to develop a polymerase chain reaction (PCR) method to identify Lactobacillus crispatus., Methods and Results: A primer set (CbsA2F-CbsA2R) for amplifying conserved regions of S-layer genes was designed to identify Lact. crispatus and the specificity of this set was compared with that of another primer set (Cri 16SI-Cri 16SII) which has been reported as a species-specific primer set targeting the 16S rRNA gene. Among species in the Lact. acidophilus A1-A4 groups, when KOD polymerase was used for amplification, the primer set CbsA2F-CbsA2R gave PCR products with Lact. crispatus strains only. However, when Taq polymerase was used, this primer set gave products with one Lact. amylovorus strain as well as with Lact. crispatus strains. The primer set Cri 16SI-Cri 16SII gave PCR products with Lact. crispatus strains and two Lact. acidophilus strains, regardless of whether the polymerase used was KOD or Taq., Conclusions: A PCR targeting the S-layer gene and amplified with KOD polymerase can identify Lact. crispatus accurately and rapidly., Significance and Impact of the Study: To the authors' knowledge, this is the first paper to provide a PCR method for the specific identification of Lact. crispatus.

Aims: This study aimed to evaluate the efficiency with which Lactobacillus crispatus JCM 5810 inhibited the adhesion of enteric pathogens to a synthetic basement membrane and to elucidate the mechanism underlying the inhibition., Methods and Results: Lactobacillus crispatus JCM 5810 inhibited the adhesion of three diarrhoeagenic Escherichia coli strains to a reconstituted basement membrane preparation called Matrigel, used as a model of a damaged intestinal tissue site. Inhibition was also observed with the use of immobilized laminin, a major component of Matrigel, but diminished after the removal of S-layer protein (CbsA) from JCM 5810 cells. The isolated CbsA inhibited the adhesion of E. coli to both Matrigel and immobilized laminin. Lactobacillus crispatus JCM 5810 and CbsA seem to inhibit pathogenic E. coli from adhering to basement membrane via competition with laminin molecules for binding sites., Conclusions: These results suggested that not only Lact. crispatus JCM 5810 cells but CbsA alone might prevent pathogens from colonizing damaged intestinal tissues., Significance and Impact of the Study: This is the first study to show the applied aspect of Lactobacillus S-layer protein.

Aims: To select adhesive strains among strains of Lactobacillus and to apply them to inhibit adhesion of food-borne pathogens., Methods and Results: Twelve Lactobacillus strains (10 from intestine) were examined for adhesion using Caco-2 cell cultures. The two most adhesive strains, Lactobacillus crispatus JCM 8779 and Lact. reuteri JCM 1081, were used to test antiadhesion activity against enterotoxigenic Escherichia coli, Salmonella typhimurium and Enterococcus faecalis strains. Adhesion of the pathogens was inhibited by both Lactobacillus strains. Adhesion of Ent. faecalis was especially strongly inhibited by JCM 8779. Although antimicrobial activity was not detected in the culture supernatant fluid by agar well diffusion assay, the supernatant fluid obtained from the harvested JCM 8779 cell suspension showed bactericidal activity against Ent. faecalis., Conclusion: The strong antiadhesion activity of JCM 8779 against Ent. faecalis appears to be due to the combined effect of both bactericidal activity and competition for attachment site., Significance and Impact of the Study: This is the first report that Lact. crispatus produces a bactericidal substance.

Lactobacillus acidophilus group and a Lact. reuteri isolated from human faeces were examined for production of antimicrobial agents against 16 strains of six species of food-borne enteric pathogenic bacteria. Several strains of Lact. gasseri showed wide inhibitory activity against the tested bacteria. Gassericin A produced by Lact. gasseri LA39 was one of the most widely active bacteriocins. It was bactericidal without causing cell lysis.

A new bacteriocin, gassericin A, was purified from the culture fluid of Lactobacillus gasseri LA39 mainly by reverse-phase (RP) chromatography. The purification of gassericin A from a modified MRS broth, in which Tween 80 had been replaced by oleic acid, resulted in a 4500-fold increase in specific activity with a 6% recovery. Gassericin A was eluted as a single peak on the chromatogram from RP-HPLC and migrated by SDS-PAGE as a single band with a molecular weight of ca. 3.8 kDa. Gassericin A, a highly hydrophobic bacteriocin, was slightly soluble in water, but its solubility was increased by adding alcohol and acetonitrile. An amino acid analysis revealed that it was composed of 45.7% hydrophobic amino acids in the total residues of 35 amino acids. Gassericin A produced in the MRS broth associated strongly with Tween 80, although several further trials of dissociation were unsuccessful.

The cells of 28 strains of the Lactobacillus acidophilus group were evaluated for hemagglutination (HA) activity. The activity was found in the surface layer (SL) protein fraction extracted by 2 M guanidine hydrochloride. The most SL proteins from the A group strains (L. acidophilus (A1), L. crispatus (A2), L. amylovorus (A3), and L. gallinarum (A4)) showed HA activity, but the proteins from the B group strains (L. gasseri (B1) and L. johnsonii (B2)) showed no activity. The SL proteins from the A group strains were composed in common of a main component having molecular mass of about 40-45 kDa on SDS-PAGE. The SL proteins from JCM 1034 strain that showed the highest HA activity was fractionated by CM-Toyopearl ion-exchange chromatography. The highest HA activity was detected in the major protein of 41 kDa. This protein was purified and shown to be composed of about 50% of hydrophobic amino acids. The HA activity of the protein (1034 lectin) was specifically inhibited by fetuin and bovine lactoferrin at the concentrations of 80 and 160 micrograms/ml, respectively. The removal of N-acetylneuraminic acid from fetuin significantly decreased the inhibitory activity.