Comparison of the frequency and complications of inappropriate antidiuretic hormone secretion in patients with septic and aseptic meningitis

Objective Due to the high prevalence of syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH). This study was carried out to evaluate the prevalence and relevant parameters of SIADH in children with septic and aseptic memingitis hospitalized at Kashan Shahid Beheshti Hospital between 1996 and 2006. Materials & Methods This descriptive study was conducted on 230 patients with meningitis hospitalized in the pediatric wards of Kashan Shahid Beheshti Hospital between 1996 and 2006. Relevant information (age, gender, type of meningitis, serum sodium and potassium, urine specific gravity (USG), blood sugar, blood urea nitrogen, serum creatinin, hydration condition) was collected from patients' records. Datawas analyzed using Mann-Whitney and K2 tests. Results Out of 230 patients with meningitis, 33 had incomplete records and only 197 patients were recruited for this study. Sixty eight cases (34.5) suffered from SIADH. It was more frequent among 1-2 year old children. According to this research, SIADH was diagnosed in 57 of the 121 patients with hyponatremia, 58.7 of the 167 patients with USG > 1.004, 74 of the 93 patients with serum osmolity < 280 mOs/L and 100 of the patients with BUN < 10 mg. Conclusion Due to the high prevalence of SIADH in septic and aseptic meningitis and its complication, it is recommended to restrict fluid therapy and monitor serum sodium, urine specific gravity and other diagnostic tests for SIADH

A Case Matched Gender Comparison Transcriptomic Screen Identifies eIF4E and eIF5 as Potential Prognostic and Tractable Biomarkers in Male Breast Cancer

Purpose: Breast cancer (BC) affects both genders, but is understudied in men. Although still rare, male BC is being diagnosed more frequently. Treatments are wholly informed by clinical studies conducted in women, based on assumptions that underlying biology is similar. Experimental design: A transcriptomic investigation of male and female BC was performed, confirming transcriptomic data in silico. Biomarkers were immunohistochemically assessed in 697 MBCs (n=477, training; n=220, validation set) and quantified in pre- and post-treatment samples from a male BC patient receiving Everolimus and PI3K/mTOR inhibitor. Results: Gender-specific gene expression patterns were identified. eIF transcripts were up-regulated in MBC. eIF4E and eIF5 were negatively prognostic for overall survival alone (Log rank; p=0.013; HR=1.77, 1.12-2.8 and p=0.035; HR=1.68, 1.03-2.74, respectively), or when co-expressed (p=0.01; HR=2.66, 1.26-5.63), confirmed in the validation set. This remained upon multivariate Cox regression analysis (eIF4E p=0.016; HR 2.38 (1.18-4.8), eIF5 p=0.022; HR 2.55 (1.14-5.7); co-expression p=0.001; HR=7.04 (2.22-22.26)). Marked reduction in eIF4E and eIF5 expression was seen post BEZ235/Everolimus, with extended survival. Conclusions: Translational initiation pathway inhibition could be of clinical utility in male BC patients overexpressing eIF4E and eIF5. With mTOR inhibitors which target this pathway now in the clinic, these biomarkers may represent new targets for therapeutic intervention, although further independent validation is required

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Annan-orientering i masskommunicerande brevtexter : en tentativ modell

The aim of this thesis is to operationalise the concept of other-orientation. Based on an explorative approach, a tentative model for analysing the marks of other-orientation is developed. The model consists of four grammatical and pragmatic categories in language: deixis, speech acts, modality, and evaluative words. The process of finding out the significant marks in each category and develop a model has been an interplay between a thorough linguistic coding, an interpretative, evaluating reading, and abductive reasoning in a step-by-step process. Theoretically the study is based on dialogism. From this perspective, the very fact that human nature is social indicates that other-orientation is a constituent component in every communicative act. For that reason, the challenge has not been to prove that other-orientation exists in texts, but to explore how a text is made interactive, contextual, dynamic and other-oriented by means of grammatical and pragmatic selectives such as words, phrases, and clauses. The data consists of eight personally addressed mass communication letters about everyday matters. Each text has its model reader in a readers’ collective. Consequently the language in the texts is construed to form a dialogue between an in-text writer and reader that share the same context, although the distance between the real writer and reader is crucial. One result of the study is the model as such, another the analyses in which the functions of other-orientation related to the four categories are presented. Moreover, the linguistic analyses show differences between texts and readers’ collectives. Texts aimed at large anonymous collectives generally feature a direct address singular you, a high rate of positive evaluative words, more responsive speech acts, and some more potential modality. In texts aimed at a small familiar collective, there is an "I" or a "we" addressing a collective "you". There are not as many evaluative words but more assertions without any evaluation or modality. When it comes to other-orientation, the categories of deixis and speech acts tend to be of greater importance compared to modality and evaluative words. It makes a difference if you address a reader with a singular or collective "you" and if you choose to interact with responsive speech acts or informative statements. These contrast ways to address a reader are of importance for the construction of genre and say a great deal about other-orientation in texts

CD11b B Cells Increase after Stroke and Regulate Microglia

Recent studies have highlighted the deleterious contributions of B cells to post-stroke recovery and cognitive decline. Different B cell subsets have been proposed on the basis of expression levels of transcription factors (e.g., T-bet) as well as specific surface proteins. CD11b (α-chain of integrin) is expressed by several immune cell types and is involved in regulation of cell motility, phagocytosis, and other essential functions of host immunity. Although B cells express CD11b, the CD11b subset of B cells has not been well characterized, especially in immune dysregulation seen with aging and after stroke. Here, we investigate the role of CD11b B cells in immune responses after stroke in young and aged mice. We evaluated the ability of CD11b B cells to influence pro- and anti-inflammatory phenotypes of young and aged microglia (MG). We hypothesized that CD11b B cells accumulate in the brain and contribute to neuroinflammation in aging and after stroke. We found that CD11b B cells are a heterogeneous subpopulation of B cells predominantly present in naive aged mice. Their frequency increases in the brain after stroke in young and aged mice. Importantly, CD11b B cells regulate MG phenotype and increase MG phagocytosis in both ex vivo and in vivo settings, likely by production of regulatory cytokines (e.g., TNF-α). As both APCs and adaptive immune cells with long-term memory function, B cells are uniquely positioned to regulate acute and chronic phases of the post-stroke immune response, and their influence is subset specific

Dysregulated Gut Homeostasis Observed Prior to the Accumulation of the Brain Amyloid-β in Tg2576 Mice

Amyloid plaques in Alzheimer&rsquo;s disease (AD) are associated with inflammation. Recent studies demonstrated the involvement of the gut in cerebral amyloid-beta (A&beta;) pathogenesis; however, the mechanisms are still not well understood. We hypothesize that the gut bears the A&beta; burden prior to brain, highlighting gut&ndash;brain axis (GBA) interaction in neurodegenerative disorders. We used pre-symptomatic (6-months) and symptomatic (15-months) Tg2576 mouse model of AD compared to their age-matched littermate WT control. We identified that dysfunction of intestinal epithelial barrier (IEB), dysregulation of absorption, and vascular A&beta; deposition in the IEB occur before cerebral A&beta; aggregation is detectible. These changes in the GBA were associated with elevated inflammatory plasma cytokines including IL-9, VEGF and IP-10. In association with reduced cerebral myelin tight junction proteins, we identified reduced levels of systemic vitamin B12 and decrease cubilin, an intestinal B12 transporter, after the development of cerebral A&beta; pathology. Lastly, we report A&beta; deposition in the intestinal autopsy from AD patients with confirmed cerebral A&beta; pathology that is not present in intestine from non-AD controls. Our data provide evidence that gut dysfunction occurs in AD and may contribute to its etiology. Future therapeutic strategies to reverse AD pathology may involve the early manipulation of gut physiology and its microbiota