Performance evaluation of the commercial aquafeeds available in the market of Pakistan on Channa marulius (Sole) / Avaliação de desempenho dos alimentos aquáticos comerciais disponíveis no mercado do Paquistão em Channa marulius (Sole)

Abstract The present study aimed to determine the effect of different levels of protein on the growth, body composition, amino acid profile and serology of Channa marulius fingerlings. The experiment was conducted in ten happas installed in earthen ponds, each stocked with 10 fishes for 90 days. Four commercial fish feeds having 25%, 30%, 32% and 40% crude protein (CP) levels were fed to fish at 3% of their wet body weight three times a day. The results of the study revealed that highest weight gain, feed conversion ratio and survival rate were observed in 30% protein feed. Meanwhile, moisture content was higher in fish fed with 30% CP feed while highest crude protein was recorded in 40% CP fed fish. Lowest fat content was observed in 32% CP feed. Amino acid profile of fish revealed better results in 30% CP feed. Total protein, glucose and globulin were also highest in fish feeding 30% CP feed, while albumin was highest in 40% CP feed. It is concluded that 30% CP feed showed better results in terms of growth, amino acid profile and serological parameters without effecting fish body composition.

Resumo O presente estudo teve como objetivo determinar o efeito de diferentes níveis de proteína sobre o crescimento, composição corporal, perfil de aminoácidos e sorologia de alevinos de Channa marulius. O experimento foi conduzido em dez happas instalados em tanques de terra, cada um abastecido com 10 peixes, por 90 dias. Quatro alimentos para peixes comerciais com níveis de 25%, 30%, 32% e 40% de proteína bruta (PB) foram dados aos peixes com 3% de seu peso corporal úmido três vezes ao dia. Os resultados do estudo revelaram que maior ganho de peso, taxa de conversão alimentar e taxa de sobrevivência foram observados em 30% de proteína alimentar. Enquanto isso, o conteúdo de umidade foi maior em peixes alimentados com 30% de PB, enquanto a proteína bruta mais alta foi registrada em peixes alimentados com 40% de PB. O menor conteúdo de gordura foi observado em rações com 32% de PB. O perfil de aminoácidos dos peixes revelou melhores resultados na ração com 30% de PB. Proteína total, glicose e globulina também foram maiores em peixes alimentados com ração com 30% de PB, enquanto a albumina foi mais alta com 40% de PB. Conclui-se que a ração com 30% de PB apresentou melhores resultados em termos de crescimento, perfil de aminoácidos e parâmetros sorológicos sem afetar a composição corporal dos peixes.

Performance evaluation of the commercial aquafeeds available in the market of Pakistan on Channa marulius (Sole)

Abstract The present study aimed to determine the effect of different levels of protein on the growth, body composition, amino acid profile and serology of Channa marulius fingerlings. The experiment was conducted in ten happas installed in earthen ponds, each stocked with 10 fishes for 90 days. Four commercial fish feeds having 25%, 30%, 32% and 40% crude protein (CP) levels were fed to fish at 3% of their wet body weight three times a day. The results of the study revealed that highest weight gain, feed conversion ratio and survival rate were observed in 30% protein feed. Meanwhile, moisture content was higher in fish fed with 30% CP feed while highest crude protein was recorded in 40% CP fed fish. Lowest fat content was observed in 32% CP feed. Amino acid profile of fish revealed better results in 30% CP feed. Total protein, glucose and globulin were also highest in fish feeding 30% CP feed, while albumin was highest in 40% CP feed. It is concluded that 30% CP feed showed better results in terms of growth, amino acid profile and serological parameters without effecting fish body composition.

Resumo O presente estudo teve como objetivo determinar o efeito de diferentes níveis de proteína sobre o crescimento, composição corporal, perfil de aminoácidos e sorologia de alevinos de Channa marulius. O experimento foi conduzido em dez happas instalados em tanques de terra, cada um abastecido com 10 peixes, por 90 dias. Quatro alimentos para peixes comerciais com níveis de 25%, 30%, 32% e 40% de proteína bruta (PB) foram dados aos peixes com 3% de seu peso corporal úmido três vezes ao dia. Os resultados do estudo revelaram que maior ganho de peso, taxa de conversão alimentar e taxa de sobrevivência foram observados em 30% de proteína alimentar. Enquanto isso, o conteúdo de umidade foi maior em peixes alimentados com 30% de PB, enquanto a proteína bruta mais alta foi registrada em peixes alimentados com 40% de PB. O menor conteúdo de gordura foi observado em rações com 32% de PB. O perfil de aminoácidos dos peixes revelou melhores resultados na ração com 30% de PB. Proteína total, glicose e globulina também foram maiores em peixes alimentados com ração com 30% de PB, enquanto a albumina foi mais alta com 40% de PB. Conclui-se que a ração com 30% de PB apresentou melhores resultados em termos de crescimento, perfil de aminoácidos e parâmetros sorológicos sem afetar a composição corporal dos peixes.

Investigating the Correlation Between Presence and Reaction Time in Mixed Reality.

Measuring presence is critical to improving user involvement and performance in Mixed Reality (MR). Presence, a crucial aspect of MR, is traditionally gauged using subjective questionnaires, leading to a lack of time-varying responses and susceptibility to user bias. Inspired by the existing literature on the relationship between presence and human performance, the proposed methodology systematically measures a user's reaction time to a visual stimulus as they interact within a manipulated MR environment. We explore the user reaction time as a quantity that can be easily measured using the systemic tools available in modern MR devices. We conducted an exploratory study (N=40) with two experiments designed to alter the users' sense of presence by manipulating place illusion and plausibility illusion. We found a significant correlation between presence scores and reaction times with a correlation coefficient -0.65, suggesting that users with a higher sense of presence responded more swiftly to stimuli. We develop a model that estimates a user's presence level using the reaction time values with high accuracy of up to 80%. While our study suggests that reaction time can be used as a measure of presence, further investigation is needed to improve the accuracy of the model.

Challenges in Assessing Blood Pressure in Adults Following Intravenous Paracetamol Infusion in the Emergency Room.

Background and objective The negligible side effects of paracetamol along with its ease of availability have catapulted paracetamol to be a widely used medication in emergency room management to reduce pain and subsequent elevations in blood pressure (BP). Our study aimed to address the challenges in informed clinical decision-making in the emergency room following paracetamol intravenous infusion. Methods This was a retrospective cross-sectional study involving the extraction of data from electronic medical records of patients who received intravenous paracetamol infusion between January 2022 and May 2022. Demographic information and BP-related data were collected for analysis. Results We initially considered a total of 162 patient records, with 132 of them eventually meeting the inclusion criteria. Among patients receiving paracetamol infusion for 15 minutes or less, 34% showed a drop of 1-5 mmHg in systolic BP (SBP), while 26% experienced a drop of 6-10 mmHg. However, infusion time longer than 16 minutes did not significantly reduce SBP. Diastolic BP (DBP) was not significantly affected by the duration of the paracetamol infusion. Analysis of the drop in SBP revealed no significant associations with age, gender, or ethnicity. Mean arterial pressure (MAP) was not significantly affected by the duration of paracetamol infusion. Conclusion Our findings suggest that intravenous paracetamol infusion does not significantly lower BP in adults in the emergency room, except for infusions of shorter durations. However, various factors, including infusion rate, patient characteristics, and concomitant medications, may influence BP measurements. The study emphasizes the need for establishing standardized criteria and conducting further research to assess intravenous paracetamol's hemodynamic effects accurately.

Canadian real-world experience of asciminib treatment in heavily pre-treated chronic myeloid leukemia (CML) patients who failed multiple lines of tyrosine kinase inhibitor (TKI) therapy.

BACKGROUND: Asciminib is a novel drug specifically targeting ABL myristoyl pocket in the ABL1 protein. METHODS: Forty one patients with chronic myeloid leukemia treated with asciminib from 2018 to 2022 were reviewed and analyzed for the efficacy and tolerability of asciminib using real-world experience data. RESULTS: The median age was 60 years (range 17-90) with a past history of a cardiovascular event in 21 patients (51%). Patients were pretreated with a median of 3 previous tyrosine kinase inhibitors (range 1-5). After a median of 12 months of asciminib (range 3-41), major molecular response (MMR) rate was 39% (n = 11/28) and 42% (n = 5/12) at 6 and 12 months, respectively. Molecular response with 2 log reduction (MR2) was noted in 54% (n = 15/28) and 50% (n = 6/12) at 6 and 12 months. The cumulative incidence of MMR and MR2 was 46.3% and 66% at 12 months. Five patients discontinued asciminib due to treatment failure (n = 3) or thrombocytopenia (n = 2). There were no cardiovascular events. Out of 7 patients treated with high dose asciminib for T315I mutation, 5 patients achieved MMR or deeper response. The event-free survival was 63% at 12 months. CONCLUSION: This study confirmed clinical efficacy and tolerability of asciminib with real-world experience.

A Case of Bullous Pemphigoid in a Five-Month-Old Female: A Rare Presentation.

Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease, characterized by the presence of tense bullae and erosions of the skin and rarely at the mucous membranes. It often presents in the elderly population, but the incidence is rare in children and infants, with few reported cases in this population in the literature. We report a rare presentation of bullous pemphigoid in a five-month-old girl who presented to our clinic.

Knowledge of and behaviors toward a gluten-free diet among women at a health sciences university.

Purpose: Gluten-free diets have gained popularity worldwide. However, little information is available regarding the knowledge of, and behaviors toward, this diet among adults in KSA. This study was aimed at addressing this knowledge gap. Methods: A cross-sectional survey was conducted in 352 women at a health sciences university in KSA. Results: Eleven percent of participants had followed a gluten-free diet at least once, 70% of whom had voluntarily tried this diet without a confirmed medical diagnosis. The main source of information regarding this diet was the internet and social media. Additionally, followers of this diet had moderate knowledge of gluten and its products yet higher knowledge than that of non-followers (65% vs 56%, P = .0055). Following a GFD was associated with an age of 25 years or older, higher education, and being employed. Although 56% of participants reported following this diet 75% or more of the time, the average calculated adherence score was low. Although 95% of the followers indicated changes in their lifestyle and social life, 71% felt better after following this diet, and only 2.6% felt worse. This self-reported results were confirmed by a calculated average quality of life score of 1.3, indicating a good quality of life after following this diet. Conclusion: This study indicated moderate knowledge and low adherence to a gluten-free diet among followers. This finding may be attributable to the high percentage of followers without a confirmed medical condition, or to the social and lifestyle changes faced by followers of GFDs. Educational programs should be introduced to the public to increase awareness of gluten-free foods and diets.

Cardiac Resynchronisation with Conduction System Pacing.

To date, biventricular pacing (BiVP) has been the standard pacing modality for cardiac resynchronisation therapy. However, it is non-physiological, with the activation spreading between the left ventricular epicardium and right ventricular endocardium. Up to one-third of patients with heart failure who are eligible for cardiac resynchronisation therapy do not derive benefit from BiVP. Conduction system pacing (CSP), which includes His bundle pacing and left bundle branch area pacing, has emerged as an alternative to BiVP for cardiac resynchronisation. There is mounting evidence supporting the benefits of CSP in achieving synchronous ventricular activation and repolarisation. The aim of this review is to summarise the current options and outcomes of CSP when used for cardiac resynchronisation in patients with heart failure.

Low postoperative perfused vessel density is associated with increased soluble endothelial cell adhesion molecules during circulatory shock after cardiac surgery.

INTRODUCTION: Microcirculatory dysfunction after cardiovascular surgery is associated with significant morbidity and worse clinical outcomes. Abnormal capillary blood flow can occur from multiple causes, including cytokine-mediated vascular endothelial injury, microthrombosis, and an inadequate balance between vasoconstriction and vasodilation. In response to proinflammatory cytokines, endothelial cells produce cellular adhesion molecules (CAMs) which regulate leukocyte adhesion, vascular permeability, and thus can mediate tissue injury. The relationship between changes in microcirculatory flow during circulatory shock and circulating adhesion molecules is unclear. The objective of this study was to compare changes in plasma soluble endothelial cell adhesion molecules (VCAM-1, ICAM-1, and E-Selectin) in patients with functional derangements in microcirculatory blood flow after cardiovascular surgery. METHODS: Adult patients undergoing elective cardiac surgery requiring cardiopulmonary bypass who exhibited postoperative shock were enrolled in the study. Sublingual microcirculation imaging was performed prior to surgery and within 2 h of ICU admission. Blood samples were taken at the time of microcirculation imaging for biomarker analysis. Plasma soluble VCAM-1, ICAM-1, and E-selectin in addition to plasma cytokines (IL-6, IL-8, and IL-10) were measured by commercially available enzyme-linked immunoassay. RESULTS: Of 83 patients with postoperative shock who were evaluated, 40 patients with clinical shock had a postoperative perfused vessel density (PVD) >1 SD above (High PVD group = 28.5 ± 2.3 mm/mm2, n = 20) or below (Low PVD = 15.5 ± 2.0 mm/mm2, n = 20) the mean postoperative PVD and were included in the final analysis. Patient groups were well matched for comorbidities, surgical, and postoperative details. Overall, there was an increase in postoperative plasma VCAM-1 and E-Selectin compared to preoperative levels, but there was no difference between circulating ICAM-1. When grouped by postoperative microcirculation, patients with poor microcirculation were found to have increased circulating VCAM-1 (2413 ± 1144 vs. 844 ± 786 ng/mL; p < 0.0001) and E-Selectin (242 ± 119 vs. 87 ± 86 ng/mL; p < 0.0001) compared to patients with increased microcirculatory blood flow. Microcirculatory flow was not associated with a difference in plasma soluble ICAM-1 (394 ± 190 vs. 441 ± 256; p = 0.52). CONCLUSIONS: Poor postoperative microcirculatory blood flow in patients with circulatory shock after cardiac surgery is associated with increased plasma soluble VCAM-1 and E-Selectin, indicating increased endothelial injury and activation compared to patients with a high postoperative microcirculatory blood flow. Circulating endothelial cell adhesion molecules may be a useful plasma biomarker to identify abnormal microcirculatory blood flow in patients with shock.

Catheter ablation of atrial fibrillation in patients with and without hypertrophic cardiomyopathy: systematic review and meta-analysis.

BACKGROUND: Atrial fibrillation (AF) is common in hypertrophic cardiomyopathy (HCM). There is limited data regarding the outcomes of AF catheter ablation in HCM patients. In this study, we aimed to synthesize all available evidence on the effectiveness of ablation of AF in patients with HCM compared to those without HCM. METHODS AND RESULTS: We systematically reviewed bibliographic databases to identify studies published through February 2023. We included cohort studies with available quantitative information on rates of recurrent atrial arrhythmias, anti-arrhythmic drug (AAD) therapy, and repeat ablation procedures after initial AF ablation in patients with vs without HCM. Estimates were combined using random-effects meta-analysis models and reported as risk ratios (RR) and 95% confidence intervals (CI). Eight studies were included in quantitative synthesis (262 HCM and 642 non-HCM patients). During median follow-up 13-54 months across studies, AF recurrence rates ranged from 13.3% to 92.9% in HCM and 7.6% to 58.8% in non-HCM patients. The pooled RR for recurrent atrial arrhythmia after the first AF ablation in HCM patients compared to non-HCM controls was 1.498 (95% CI = 1.305-1.720; P < 0.001). During follow-up, HCM patients more often required AAD therapy (RR = 2.844; 95% CI = 1.713-4.856; P < 0.001) and repeat AF ablation (RR = 1.544; 95% CI = 1.070-2.228; P = 0.02). The pooled RR for recurrent atrial arrhythmias after the last AF ablation was higher in patients with HCM than those without HCM (RR = 1.607; 95% CI = 1.235-2.090; P < 0.001). CONCLUSIONS: Compared to non-HCM patients, those with HCM had higher rates of recurrent atrial arrhythmias, AAD use, and need for repeat AF ablation after initial ablation of AF.

Divergent androgenic modulation of SARS-CoV-2 infection cooperates with dysregulated immune response to dictate worse COVID-19 outcomes in men.

BACKGROUND: Sex-determined differences are rarely addressed in the management of diseases, despite well-known contrasting outcomes between female and male patients. In COVID-19 there is a remarkable disparity, with higher rates of mortality and more severe acute disease in men compared to women, who are mostly affected by long COVID-19. Furthermore, whether androgens play a protective or detrimental role in COVID-19 is still a matter of debate. Hence, the adequate management of the disease, especially regarding men presenting acute disease aggravation, still needs important data to elucidate the interplay between sex hormones and host immune responses that drive the worse evolution in male patients. METHODS: A cohort of 92 controls and 198 non-severe and severe COVID-19 patients, from both sexes, was assessed for clinical outcomes, plasma steroids, gonadotropins, sex hormone binding globulin (SHBG) and immune mediators, before vaccination. These data were correlated with the global gene expression of blood leukocytes. The androgen receptor (AR) signaling pathway was investigated by transcriptomics and tracheal aspirate was obtained from severe patients for SARS-COV-2 quantification in the respiratory tract. The interplay among clinical, endocrine and immunological data deciphered the sex differences in COVID-19. Importantly, statistical analyses, using 95% confidence interval, considered confounding factors such as age and comorbidities, to definitely parse the role of androgens in the disease outcome. RESULTS: There were notable contrasting levels of testosterone and dihydrotestosterone (DHT) throughout the disease course in male but not female patients. Inflammatory mediators presented significant negative correlations with testosterone, which was partially dependent on age and diabetes in men. Male subjects with severe COVID-19 had a significant up regulation of the AR signaling pathway, including modulation of TMPRSS2 and SRD5A1 genes, which are related to the viral infection and DHT production. Indeed, men had a higher viral load in the tracheal aspirate and levels of DHT were associated with increased relative risk of death. In contrast, the testosterone hormone, which was notably reduced in severe disease, was significantly related with susceptibility to COVID-19 worsening in male patients. Secondary hypogonadism was ruled out in the male severe COVID-19 subjects, as FSH, LH, and SHBG levels were not significantly altered. Instead, these subjects tended to have increased gonadotropin levels. Most interestingly, in this study we identified, for the first time, combined sets of clinical and immunoendocrine parameters that together predicted progression from non-severe to severe COVID-19 in men. One of the limitations of our study was the low or undetectable levels of DHT in many patients. Then, the evaluation of enzymes related to biosynthesis and signaling by androgens was mandatory and reiterated our findings. CONCLUSIONS: These original results unraveled the disease immunoendocrine regulation, despite vaccination or comorbidities and pointed to the fundamental divergent role of the androgens testosterone and DHT in the determination of COVID-19 outcomes in men. Therefore, sex-specific management of the dysregulated responses, treatments or public health measures should be considered for the control of COVID-19 pandemic.

Investigating the Utility of the SOFA Score and Creating a Modified SOFA Score for Predicting Mortality in the Intensive Care Units in a Tertiary Hospital in Jordan.

Background: The utility of the Sequential Organ Failure Assessment (SOFA) score in predicting mortality in the intensive care unit (ICU) has been demonstrated before, but serial testing in various settings is required to validate and improve the score. This study examined the utility of the SOFA score in predicting mortality in Jordanian ICU patients and aimed to find a modified score that required fewer laboratory tests. Methods: A prospective observational study was conducted at Jordan University Hospital (JUH). All adult patients admitted to JUH ICUs between June and December 2020 were included in the study. SOFA scores were measured daily during the whole ICU stay. A modified SOFA score (mSOFA) was constructed from the available laboratory, clinical, and demographic data. The performance of the SOFA, mSOFA, qSOFA, and SIRS in predicting ICU mortality was assessed using the area under the receiver operating characteristic curve (AUROC). Results: 194 patients were followed up. SOFA score (mean ± SD) at admission was significantly higher in non-survivors (7.5 ± 3.9) compared to survivors (2.4 ± 2.2) and performed the best in predicting ICU mortality (AUROC = 0.8756, 95% CI: 0.8117-0.9395) compared to qSOFA (AUROC = 0.746, 95% CI: 0.655-0.836) and SIRS (AUROC = 0.533, 95% CI: 0.425-0.641). The constructed mSOFA included points for the hepatic and CNS SOFA scores, in addition to one point each for the presence of chronic kidney disease or the use of breathing support; it performed as well as the SOFA score in this cohort or better than the SOFA score in a subgroup of patients with heart disease. Conclusion: SOFA score was a good predictor of mortality in a Jordanian ICU population and better than qSOFA, while SIRS could not predict mortality. Furthermore, the proposed mSOFA score which employed fewer laboratory tests could be used after validation from larger studies.

Safety and immunogenicity of rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine against SARS-CoV-2 in healthy adolescents: an open-label, non-randomized, multicenter, phase 1/2, dose-escalation study.

To protect young individuals against SARS-CoV-2 infection, we conducted an open-label, prospective, non-randomised dose-escalation Phase 1/2 clinical trial to evaluate the immunogenicity and safety of the prime-boost "Sputnik V" vaccine administered at 1/10 and 1/5 doses to adolescents aged 12-17 years. The study began with the vaccination of the older cohort (15-to-17-year-old participants) with the lower (1/10) dose of vaccine and then expanded to the whole group (12-to-17-year-old participants). Next, 1/5 dose was used according to the same scheme. Both doses were well tolerated by all age groups. No serious or severe adverse events were detected. Most of the solicited adverse reactions were mild. No significant differences in total frequencies of adverse events were registered between low and high doses in age-pooled groups (69.6% versus 66.7%). In contrast, the 1/5 dose induced significantly higher humoral and T cell-mediated immune responses than the 1/10 dose. The 1/5 vaccine dose elicited higher antigen-binding (both S and RBD-specific) as well as virus-neutralising antibody titres at the maximum of response (day 42), also resulting in a statistically significant difference at a distanced timepoint (day 180) compared to the 1/10 vaccine dose. Higher dose resulted in increased cross-neutralization of Delta and Omicron variants. Clinical Trial Registration: ClinicalTrials.gov, NCT04954092, LP-007632.

Plasma Sphingomyelin Disturbances: Unveiling Its Dual Role as a Crucial Immunopathological Factor and a Severity Prognostic Biomarker in COVID-19.

SARS-CoV-2 infection triggers distinct patterns of disease development characterized by significant alterations in host regulatory responses. Severe cases exhibit profound lung inflammation and systemic repercussions. Remarkably, critically ill patients display a "lipid storm", influencing the inflammatory process and tissue damage. Sphingolipids (SLs) play pivotal roles in various cellular and tissue processes, including inflammation, metabolic disorders, and cancer. In this study, we employed high-resolution mass spectrometry to investigate SL metabolism in plasma samples obtained from control subjects (n = 55), COVID-19 patients (n = 204), and convalescent individuals (n = 77). These data were correlated with inflammatory parameters associated with the clinical severity of COVID-19. Additionally, we utilized RNAseq analysis to examine the gene expression of enzymes involved in the SL pathway. Our analysis revealed the presence of thirty-eight SL species from seven families in the plasma of study participants. The most profound alterations in the SL species profile were observed in patients with severe disease. Notably, a predominant sphingomyelin (SM d18:1) species emerged as a potential biomarker for COVID-19 severity, showing decreased levels in the plasma of convalescent individuals. Elevated SM levels were positively correlated with age, hospitalization duration, clinical score, and neutrophil count, as well as the production of IL-6 and IL-8. Intriguingly, we identified a putative protective effect against disease severity mediated by SM (d18:1/24:0), while ceramide (Cer) species (d18:1/24:1) and (d18:1/24:0)were associated with increased risk. Moreover, we observed the enhanced expression of key enzymes involved in the SL pathway in blood cells from severe COVID-19 patients, suggesting a primary flow towards Cer generation in tandem with SM synthesis. These findings underscore the potential of SM as a prognostic biomarker for COVID-19 and highlight promising pharmacological targets. By targeting sphingolipid pathways, novel therapeutic strategies may emerge to mitigate the severity of COVID-19 and improve patient outcomes.

SUFU promotes GLI activity in a Hedgehog-independent manner in pancreatic cancer.

Aberrant activation of the Hedgehog (Hh) signaling pathway, through which the GLI family of transcription factors (TF) is stimulated, is commonly observed in cancer cells. One well-established mechanism of this increased activity is through the inactivation of Suppressor of Fused (SUFU), a negative regulator of the Hh pathway. Relief from negative regulation by SUFU facilitates GLI activity and induction of target gene expression. Here, we demonstrate a novel role for SUFU as a promoter of GLI activity in pancreatic ductal adenocarcinoma (PDAC). In non-ciliated PDAC cells unresponsive to Smoothened agonism, SUFU overexpression increases GLI transcriptional activity. Conversely, knockdown (KD) of SUFU reduces the activity of GLI in PDAC cells. Through array PCR analysis of GLI target genes, we identified B-cell lymphoma 2 (BCL2) among the top candidates down-regulated by SUFU KD. We demonstrate that SUFU KD results in reduced PDAC cell viability, and overexpression of BCL2 partially rescues the effect of reduced cell viability by SUFU KD. Further analysis using as a model GLI1, a major TF activator of the GLI family in PDAC cells, shows the interaction of SUFU and GLI1 in the nucleus through previously characterized domains. Chromatin immunoprecipitation (ChIP) assay shows the binding of both SUFU and GLI1 at the promoter of BCL2 in PDAC cells. Finally, we demonstrate that SUFU promotes GLI1 activity without affecting its protein stability. Through our findings, we propose a novel role of SUFU as a positive regulator of GLI1 in PDAC, adding a new mechanism of Hh/GLI signaling pathway regulation in cancer cells.

Brain atrophy and cognitive decline in bipolar disorder: Influence of medication use, symptomatology and illness duration.

Bipolar disorder (BPD) is a chronic condition characterized by recurrent episodes of mania and depression. To date, the association of biological and psychopathological processes in BPD has not been extensively studied on a cognitive and cortical basis at the same time. We investigated whether brain atrophy (in prefrontal, temporal and occipital cortices) was associated with cognitive, biological and clinical processes in patients with BPD and healthy controls (HCs). A total of 104 participants (56 with BPD) completed tasks that measured attention, memory, information processing speed, inhibitory control, visuospatial working memory and cognitive flexibility. In addition, structural brain scans were obtained using high-resolution MRI. Outcomes of the measurements were examined using robust multiple mediation analyses. BPD patients showed greater cortical atrophy across all regions of interest when compared to HCs, linked to cognitive decline. BPD patients had slower reaction times and markedly increased errors of commission on the tasks. The outcomes were significantly influenced by medication use, symptomatology and illness duration. The findings showcase the complexity of brain structures and networks as well as the physiological mechanisms underlying diverse BPD symptomatology and endophenotypes. These differences were pronounced in patients with BPD, motivating further investigations of pathophysiological mechanisms involved in brain atrophy and cognitive decline.

Anatomy and Pathology of the Cardiac Conduction System.

The cardiac conduction system is formed of histologically and electrophysiologically distinct specialized tissues uniquely located in the human heart. Understanding the anatomy and pathology of the cardiac conduction system is imperative to an interventional electrophysiologist to perform safe ablation and device therapy for the management of cardiac arrhythmias and heart failure. The current review summarizes the normal and developmental anatomy of the cardiac conduction system, its variation in the normal heart and congenital anomalies, and its pathology and discusses important clinical pearls for the proceduralist.