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In recent years, researchers focused on introducing discrete type distributions which satisfy the necessary demand to model the complex performance of the real data sets. In this paper, a discrete inverted Kumaraswamy distribution, which is a discrete version of the continuous inverted Kumaraswamy distribution, is derived using the general approach of discretization of a continuous distribution. The new discrete inverted Kumaraswamy distribution can be applied efficiently in discrete lifetime and count data. Some important distributional and reliability properties of discrete inverted Kumaraswamy distribution such as hazard rate, moments, quantiles, order statistics and some transformations are obtained. Maximum likelihood and Bayesian approaches are applied under Type-II censored samples for estimating the parameters, survival, hazard rate and alternative hazard rate functions. Confidence and credible intervals for the parameters are obtained. A simulation study is carried out to illustrate the theoretical results of the maximum likelihood and Bayesian estimation. Finally, the performance of the new distribution is compared with some distributions using three real data sets to illustrate the suitability and flexibility of the proposed model. [ABSTRACT FROM AUTHOR] more...

A recent study published in the journal Endoscopy evaluated the effectiveness of a cloud-based artificial intelligence (AI) polyp detection system called CADDIE in improving the detection of colorectal polyps during colonoscopy. The study involved 739 patients and 32 endoscopists from 9 UK hospitals. The results showed that the CADDIE system significantly increased the adenoma detection rate (ADR) compared to standard of care (SOC), with a higher detection rate in the proximal colon. Additionally, more adenomas were removed per colonoscopy in the CADDIE group. The study suggests that the cloud-based AI system can improve polyp detection in routine clinical settings, even when performed by non-expert colonoscopists. [Extracted from the article] more...

The article discusses a randomized controlled trial of a cloud-based artificial intelligence (AI) computer-aided diagnosis (CADx) system called CADDIE. The study aimed to assess the performance of the CADDIE system when used by non-expert endoscopists in detecting polyps during colonoscopy. The results showed that the CADDIE system had a higher accuracy in diagnosing polyps compared to human endoscopists alone, both overall and for small and diminutive polyps. The study concludes that further research is needed to optimize the performance of non-expert endoscopists using CADx systems. [Extracted from the article] more...

Objective:To study the possible damage to the vestibular system in patients with post-mumps sensorineural hearing loss.Methods:Nineteen patients with recent mumps infection participated in the study. All patients had unilateral profound sensorineural hearing loss or total hearing loss. Patients were subjected to video-nystagmography and vestibular-evoked myogenic potential testing.Results:Eight patients (42.1 per cent) had normal video-nystagmography results and intact vestibular-evoked myogenic potentials on both sides, whereas the other 11 patients (57.9 per cent) had vestibular lesions in the form of marked canal weakness and absent vestibular-evoked myogenic potential responses on the same side as hearing loss. The overall findings indicated a peripheral site for the lesions.Conclusion:The majority of patients with post-mumps sensorineural hearing loss had peripheral vestibular pathology in the same ear as hearing loss. Further research should be directed to saving the inner ear following mumps infection. [ABSTRACT FROM PUBLISHER] more...

Background & Aims: In 2018, the World Endoscopy Organization (WEO) introduced standardized methods for calculating post-colonoscopy colorectal cancer-3yr rates (PCCRC-3yr). This systematic review aimed to calculate the global PCCRC-3yr according to the WEO methodology, its change over time, and to measure the association between risk factors and PCCRC occurrences., Methods: We searched 5 databases from inception until January 2024 for PCCRC-3yr studies that strictly adhered to the WEO methodology. The overall pooled PCCRC-3yr was calculated. For risk factors and time-trend analyses, the pooled PCCRC-3yr and odds ratios (ORs) of subgroups were compared., Results: Several studies failed to adhere to the WEO methodology. Eight studies from 4 Western European and 2 Northern American countries were included, totalling 220,106 detected-colorectal cancers (CRCs) and 18,148 PCCRCs between 2002 and 2017. The pooled Western World PCCRC-3yr was 7.5% (95% confidence interval [CI], 6.4%-8.7%). The PCCRC-3yr significantly (P < .05) decreased from 7.9% (95% CI, 6.6%-9.4%) in 2006 to 6.7% (95% CI, 6.1%-7.3%) in 2012 (OR, 0.79; 95% CI, 0.72-0.87). There were significantly higher rates for people with inflammatory bowel disease (PCCRC-3yr, 29.3%; OR, 6.17; 95% CI, 4.73-8.06), prior CRC (PCCRC-3yr, 29.8%; OR, 3.03; 95% CI, 1.34-4.72), proximal CRC (PCCRC-3yr, 8.6%; OR, 1.51; 95% CI, 1.41-1.61), diverticular disease (PCCRC 3-yr, 11.6%; OR, 1.74; 95% CI, 1.37-2.10), and female sex (PCCRC-3yr, 7.9%; OR, 1.15; 95% CI, 1.11-1.20)., Conclusion: According to the WEO methodology, the Western World PCCRC-3yr was 7.5%. Reassuringly, this has decreased over time, but further work is required to identify the reasons for PCCRCs, especially in higher-risk groups. We devised a WEO methodology checklist to increase its adoption and standardise the categorization of patients in future PCCRC-3yr studies., (Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.) more...

Background: The introduction of large language models (LLMs) into clinical practice promises to improve patient education and empowerment, thereby personalizing medical care and broadening access to medical knowledge. Despite the popularity of LLMs, there is a significant gap in systematized information on their use in patient care. Therefore, this systematic review aims to synthesize current applications and limitations of LLMs in patient care., Methods: We systematically searched 5 databases for qualitative, quantitative, and mixed methods articles on LLMs in patient care published between 2022 and 2023. From 4349 initial records, 89 studies across 29 medical specialties were included. Quality assessment was performed using the Mixed Methods Appraisal Tool 2018. A data-driven convergent synthesis approach was applied for thematic syntheses of LLM applications and limitations using free line-by-line coding in Dedoose., Results: We show that most studies investigate Generative Pre-trained Transformers (GPT)-3.5 (53.2%, n = 66 of 124 different LLMs examined) and GPT-4 (26.6%, n = 33/124) in answering medical questions, followed by patient information generation, including medical text summarization or translation, and clinical documentation. Our analysis delineates two primary domains of LLM limitations: design and output. Design limitations include 6 second-order and 12 third-order codes, such as lack of medical domain optimization, data transparency, and accessibility issues, while output limitations include 9 second-order and 32 third-order codes, for example, non-reproducibility, non-comprehensiveness, incorrectness, unsafety, and bias., Conclusions: This review systematically maps LLM applications and limitations in patient care, providing a foundational framework and taxonomy for their implementation and evaluation in healthcare settings., Competing Interests: Competing interests: JNK declares consulting services for Owkin, France; DoMore Diagnostics, Norway; Panakeia, UK, and Scailyte, Basel, Switzerland; furthermore JNK holds shares in Kather Consulting, Dresden, Germany; and StratifAI GmbH, Dresden, Germany, and has received honoraria for lectures and advisory board participation by AstraZeneca, Bayer, Eisai, MSD, BMS, Roche, Pfizer and Fresenius. DT holds shares in StratifAI GmbH, Dresden, Germany and has received honoraria for lectures by Bayer. KKB reports grants from the European Union (101079894) and Wilhelm-Sander Foundation; participation on a Data Safety Monitoring Board or Advisory Board for the EU Horizon 2020 LifeChamps project (875329) and the EU IHI Project IMAGIO (101112053); speaker Fees for Canon Medical Systems Corporation and GE HealthCare. RK receives medical consultancy fees from Odin Vision. The remaining authors declare no competing interests., (© 2025. The Author(s).) more...

Gasotransmitters play crucial roles in regulating many physiological processes, including cell signaling, cellular proliferation, angiogenesis, mitochondrial function, antioxidant production, nervous system functions and immune responses. Hydrogen sulfide (H 2 S) is the most recently identified gasotransmitter, which is characterized by its biphasic behavior. At low concentrations, H 2 S promotes cellular bioenergetics, whereas at high concentrations, it can exert cytotoxic effects. Cystathionine β-synthetase (CBS), cystathionine-γ-lyase (CSE), 3-mercaptopyruvate sulfurtransferase (3-MST), and cysteinyl-tRNA synthetase 2 (CARS2) are pivotal players in H 2 S biosynthesis in mammalian cells and tissues. The focus of this review is the regulation of the various pathways involved in H 2 S metabolism in various forms of cancer. Key enzymes in this process include the sulfide oxidation unit (SOU), which includes sulfide:quinone oxidoreductase (SQOR), human ethylmalonic encephalopathy protein 1 (hETHE1), rhodanese, sulfite oxidase (SUOX/SO), and cytochrome c oxidase (CcO) enzymes. Furthermore, the potential role of H 2 S methylation processes mediated by thiol S-methyltransferase (TMT) and thioether S-methyltransferase (TEMT) is outlined in cancer biology, with potential opportunities for targeting them for clinical translation. In order to understand the role of H 2 S in oncogenesis and tumor progression, one must appreciate the intricate interplay between H 2 S-synthesizing and H 2 S-catabolizing enzymes. more...

Colorectal cancer is one of the most common cancers in the world. While colonoscopy is an effective screening technique, navigating an endoscope through the colon to detect polyps is challenging. A 3D map of the observed surfaces could enhance the identification of unscreened colon tissue and serve as a training platform. However, reconstructing the colon from video footage remains difficult. Learning-based approaches hold promise as robust alternatives, but necessitate extensive datasets. Establishing a benchmark dataset, the 2022 EndoVis sub-challenge SimCol3D aimed to facilitate data-driven depth and pose prediction during colonoscopy. The challenge was hosted as part of MICCAI 2022 in Singapore. Six teams from around the world and representatives from academia and industry participated in the three sub-challenges: synthetic depth prediction, synthetic pose prediction, and real pose prediction. This paper describes the challenge, the submitted methods, and their results. We show that depth prediction from synthetic colonoscopy images is robustly solvable, while pose estimation remains an open research question., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Danail Stoyanov reports financial support was provided by Medtronic plc. Danail Stoyanov reports a relationship with Odin Medical Ltd. that includes: equity or stocks. Laurence Lovat and Rawen Kader report a relationship with Olympus Corporation that includes: consulting or advisory., (Copyright © 2024. Published by Elsevier B.V.) more...

Few studies showed that neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), total tubulin-associated unit (TAU), and ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) may be related to neurological manifestations and severity during and after SARS-CoV-2 infection. The objective of this work was to investigate the relationship among nervous system biomarkers (NfL, TAU, GFAP, and UCH-L1), biochemical parameters, and viral loads with heterogeneous outcomes in a cohort of severe COVID-19 patients admitted in Intensive Care Unit (ICU) of a university hospital. For that, 108 subjects were recruited within the first 5 days at ICU. In parallel, 16 mild COVID-19 patients were enrolled. Severe COVID-19 group was divided between "deceased" and "survivor." All subjects were positive for SARS-CoV-2 detection. NfL, total TAU, GFAP, and UCH-L1 quantification in plasma was performed using SIMOA SR-X platform. Of 108 severe patients, 36 (33.33%) presented neurological manifestation and 41 (37.96%) died. All four biomarkers - GFAP, NfL, TAU, and UCH-L1 - were significantly higher among deceased patients in comparison to survivors (p < 0.05). Analyzing biochemical biomarkers, higher Peak Serum Ferritin, D-Dimer Peak, Gamma-glutamyltransferase, and C-Reactive Protein levels were related to death (p < 0.0001). In multivariate analysis, GFAP, NfL, TAU, UCH-L1, and Peak Serum Ferritin levels were correlated to death. Regarding SARS-CoV-2 viral load, no statistical difference was observed for any group. Thus, Ferritin, NFL, GFAP, TAU, and UCH-L1 are early biomarkers of severity and lethality of SARS-COV-2 infection and may be important tools for therapeutic decision-making in the acute phase of disease., (© 2023. The Author(s).) more...

Background and Aims: Inflammatory bowel disease [IBD] is associated with high rates of post-colonoscopy colorectal cancer [PCCRC], but further in-depth qualitative analyses are required to determine whether they result from inadequate surveillance or aggressive IBD cancer evolution., Methods: All IBD patients who had a colorectal cancer [CRC] diagnosed between January 2015 and July 2019 and a recent [<4 years] surveillance colonoscopy at one of four English hospital trusts underwent root cause analyses as recommended by the World Endoscopy Organisation to identify plausible PCCRC causative factors., Results: In total, 61% [n = 22/36] of the included IBD CRCs were PCCRCs. They developed in patients with high cancer risk factors [77.8%; n = 28/36] requiring annual surveillance, yet 57.1% [n = 20/35] had inappropriately delayed surveillance. Most PCCRCs developed in situations where [i] an endoscopically unresectable lesion was detected [40.9%; n = 9/22], [ii] there was a deviation from the planned management pathway [40.9%; n = 9/22], such as service-, clinician- or patient-related delays in acting on a detected lesion, or [iii] lesions were potentially missed as they were typically located within areas of active inflammation or post-inflammatory change [36.4%; n = 8/22]., Conclusions: IBD PCCRC prevention will require more proactive strategies to reduce endoscopic inflammatory burden, and to improve lesion optical characterization, adherence to recommended surveillance intervals, and patient acceptance of prophylactic colectomy. However, the significant proportion appearing to originate from non-adenomatous-looking mucosa which fail to yield neoplasia on biopsy yet display aggressive cancer evolution highlights the limitations of current surveillance. Emerging molecular biomarkers may play a role in enhancing cancer risk stratification in future clinical practice., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. 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.) more...

Introduction: Hydrogen sulfide (H 2 S) has been recently scrutinized for its critical role in aggravating breast cancer (BC) tumorigenicity. Several cancers aberrantly express H 2 S synthesizing enzymes; Cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE). However, their levels and interdependence in BC require further studies., Objectives: Firstly, this study aimed to demonstrate a comparative expression profile of H 2 S synthesizing enzymes in BC vs normal tissue. Moreover, to investigate the reciprocal relationship between CBS and CSE and highlight the importance of dual targeting. Finally, to search for a valid dual repressor of the H 2 S synthesizing enzymes that could cease H 2 S production and reduce TNBC pathogenicity., Methods: Pairwise analysis of tumor vs. normal tissues of 40 BC patients was carried out. The TNBC cell line MDA-MB-231 was transfected with oligonucleotides to study the H 2 S mediated molecular mechanisms. In silico screening was performed to identify dual regulator(s) for CBS and CSE. Gene expression analysis was performed using qRT-PCR and was confirmed on protein level using Western blot. TNBC hallmarks were evaluated using MTT, migration, and clonogenicity assays. H 2 S levels were detected using a AzMc fluorescent probe., Results: BC tissues exhibited elevated levels of both CBS and CSE. Interestingly, upon CBS knockdown, CSE levels increased compensating for H 2 S production in TNBC cells, underlining the importance of dually targeting both enzymes in TNBC. In silico screening suggested miR-939-5p as a regulator of both CBS and CSE with high binding scores. Low expression levels of miR-939-5p were found in BC tissues, especially the aggressive subtypes. Ectopic expression of miR-939-5p significantly repressed CBS and CSE transcript and protein levels, diminished H 2 S production and attenuated TNBC hallmarks. Moreover, it improved the immune surveillance potency of TNBC cells through up regulating the NKG2D ligands, MICB and ULBP2 and reducing the immune suppressive cytokine IL-10., Conclusion: This study sheds light on the reciprocal relationship between CBS and CSE and on the importance of their dual targeting, particularly in TNBC. It also postulates miR-939-5p as a potent dual repressor for CBS and CSE overcoming their redundancy in H 2 S production, a mechanism that can potentially attenuate TNBC oncogenicity and improves the immunogenic response., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.) more...

Objectives: Convolutional neural networks (CNN) for computer-aided diagnosis of polyps are often trained using high-quality still images in a single chromoendoscopy imaging modality with sessile serrated lesions (SSLs) often excluded. This study developed a CNN from videos to classify polyps as adenomatous or nonadenomatous using standard narrow-band imaging (NBI) and NBI-near focus (NBI-NF) and created a publicly accessible polyp video database., Methods: We trained a CNN with 16,832 high and moderate quality frames from 229 polyp videos (56 SSLs). It was evaluated with 222 polyp videos (36 SSLs) across two test-sets. Test-set I consists of 14,320 frames (157 polyps, 111 diminutive). Test-set II, which is publicly accessible, 3317 video frames (65 polyps, 41 diminutive), which was benchmarked with three expert and three nonexpert endoscopists., Results: Sensitivity for adenoma characterization was 91.6% in test-set I and 89.7% in test-set II. Specificity was 91.9% and 88.5%. Sensitivity for diminutive polyps was 89.9% and 87.5%; specificity 90.5% and 88.2%. In NBI-NF, sensitivity was 89.4% and 89.5%, with a specificity of 94.7% and 83.3%. In NBI, sensitivity was 85.3% and 91.7%, with a specificity of 87.5% and 90.0%, respectively. The CNN achieved preservation and incorporation of valuable endoscopic innovations (PIVI)-1 and PIVI-2 thresholds for each test-set. In the benchmarking of test-set II, the CNN was significantly more accurate than nonexperts (13.8% difference [95% confidence interval 3.2-23.6], P = 0.01) with no significant difference with experts., Conclusions: A single CNN can differentiate adenomas from SSLs and hyperplastic polyps in both NBI and NBI-NF. A publicly accessible NBI polyp video database was created and benchmarked., (© 2023 The Authors. Digestive Endoscopy published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.) more...

Colorectal cancer is the third most common type of cancer with almost two million new cases worldwide. They develop from neoplastic polyps, most commonly adenomas, which can be removed during colonoscopy to prevent colorectal cancer from occurring. Unfortunately, up to a quarter of polyps are missed during colonoscopies. Studies have shown that polyp detection during a procedure correlates with the time spent searching for polyps, called the withdrawal time. The different phases of the procedure (cleaning, therapeutic, and exploration phases) make it difficult to precisely measure the withdrawal time, which should only include the exploration phase. Separating this from the other phases requires manual time measurement during the procedure which is rarely performed. In this study, we propose a method to automatically detect the cecum, which is the start of the withdrawal phase, and to classify the different phases of the colonoscopy, which allows precise estimation of the final withdrawal time. This is achieved using a Resnet for both detection and classification trained with two public datasets and a private dataset composed of 96 full procedures. Out of 19 testing procedures, 18 have their withdrawal time correctly estimated, with a mean error of 5.52 seconds per minute per procedure., Competing Interests: D.S: Odin Vision Ltd (I, S), D.S: Digital Surgery Ltd (E), L.L: Odin Vision Ltd (I)., (Published by Optica Publishing Group under the terms of the Creative Commons Attribution 4.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI.) more...

Background and Aim: Lack of visual recognition of colorectal polyps may lead to interval cancers. The mechanisms contributing to perceptual variation, particularly for subtle and advanced colorectal neoplasia, have scarcely been investigated. We aimed to evaluate visual recognition errors and provide novel mechanistic insights., Methods: Eleven participants (seven trainees and four medical students) evaluated images from the UCL polyp perception dataset, containing 25 polyps, using eye-tracking equipment. Gaze errors were defined as those where the lesion was not observed according to eye-tracking technology. Cognitive errors occurred when lesions were observed but not recognized as polyps by participants. A video study was also performed including 39 subtle polyps, where polyp recognition performance was compared with a convolutional neural network., Results: Cognitive errors occurred more frequently than gaze errors overall (65.6%), with a significantly higher proportion in trainees (P = 0.0264). In the video validation, the convolutional neural network detected significantly more polyps than trainees and medical students, with per-polyp sensitivities of 79.5%, 30.0%, and 15.4%, respectively., Conclusions: Cognitive errors were the most common reason for visual recognition errors. The impact of interventions such as artificial intelligence, particularly on different types of perceptual errors, needs further investigation including potential effects on learning curves. To facilitate future research, a publicly accessible visual perception colonoscopy polyp database was created., (© 2023 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.) more...

Lynch syndrome (LS) is an inherited cancer predisposition syndrome associated with high lifetime risk of developing tumours, most notably colorectal and endometrial. It arises in the context of pathogenic germline variants in one of the mismatch repair genes, that are necessary to maintain genomic stability. LS remains underdiagnosed in the population despite national recommendations for empirical testing in all new colorectal and endometrial cancer cases. There are now well-established colorectal cancer surveillance programmes, but the high rate of interval cancers identified, coupled with a paucity of high-quality evidence for extra-colonic cancer surveillance, means there is still much that can be achieved in diagnosis, risk-stratification and management. The widespread adoption of preventative pharmacological measures is on the horizon and there are exciting advances in the role of immunotherapy and anti-cancer vaccines for treatment of these highly immunogenic LS-associated tumours. In this review, we explore the current landscape and future perspectives for the identification, risk stratification and optimised management of LS with a focus on the gastrointestinal system. We highlight the current guidelines on diagnosis, surveillance, prevention and treatment and link molecular disease mechanisms to clinical practice recommendations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Williams, Hadjinicolaou, Norton, Kader and Lovat.) more...

Background and Aims: We aimed to develop a computer-aided characterization system that could support the diagnosis of dysplasia in Barrett's esophagus (BE) on magnification endoscopy., Methods: Videos were collected in high-definition magnification white-light and virtual chromoendoscopy with i-scan (Pentax Hoya, Japan) imaging in patients with dysplastic and nondysplastic BE (NDBE) from 4 centers. We trained a neural network with a Resnet101 architecture to classify frames as dysplastic or nondysplastic. The network was tested on 3 different scenarios: high-quality still images, all available video frames, and a selected sequence within each video., Results: Fifty-seven patients, each with videos of magnification areas of BE (34 dysplasia, 23 NDBE), were included. Performance was evaluated by a leave-1-patient-out cross-validation method. In all, 60,174 (39,347 dysplasia, 20,827 NDBE) magnification video frames were used to train the network. The testing set included 49,726 i-scan-3/optical enhancement magnification frames. On 350 high-quality still images, the network achieved a sensitivity of 94%, specificity of 86%, and area under the receiver operator curve (AUROC) of 96%. On all 49,726 available video frames, the network achieved a sensitivity of 92%, specificity of 82%, and AUROC of 95%. On a selected sequence of frames per case (total of 11,471 frames), we used an exponentially weighted moving average of classifications on consecutive frames to characterize dysplasia. The network achieved a sensitivity of 92%, specificity of 84%, and AUROC of 96%. The mean assessment speed per frame was 0.0135 seconds (SD ± 0.006)., Conclusion: Our network can characterize BE dysplasia with high accuracy and speed on high-quality magnification images and sequence of video frames, moving it toward real-time automated diagnosis., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.) more...

Colonoscopy remains the gold standard investigation for colorectal cancer screening as it offers the opportunity to both detect and resect pre-cancerous polyps. Computer-aided polyp characterisation can determine which polyps need polypectomy and recent deep learning-based approaches have shown promising results as clinical decision support tools. Yet polyp appearance during a procedure can vary, making automatic predictions unstable. In this paper, we investigate the use of spatio-temporal information to improve the performance of lesions classification as adenoma or non-adenoma. Two methods are implemented showing an increase in performance and robustness during extensive experiments both on internal and openly available benchmark datasets., Competing Interests: D.S: Odin Vision Ltd (I, S), D.S: Digital Surgery Ltd (E), L.L: Odin Vision Ltd (I)., (Published by Optica Publishing Group under the terms of the Creative Commons Attribution 4.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI.) more...

Background and Objectives : The objective of this study is to examine the effect of the BNT162b2 vaccine on systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and pulse pressure (PP) before and 15 min after two doses that were given 21 days apart. Materials and Methods : This active surveillance study of vaccine safety was conducted on 15 and 16 March (for the first dose) and 5 and 6 April (for the second dose) 2021 in an academic hospital. For both doses, SBP, DBP, MAP, and PP levels were measured before and 15 min after both doses were given to healthcare workers over the age of 18. The results of the study were based on measurements of the mean blood pressure (BP), the mean changes in BP, and the BP trends. Results : In total, 287 individuals received the vaccine. After the first dose, 25% ( n = 72) of individuals had a decrease in DBP of at least 10 mmHg (mean DBP decrease: 15 mmHg, 95% CI: 14-17 mmHg), and after the second dose it was 12.5% (mean DBP decrease: 13 mmHg, 95% CI: 12-15 mmHg). After the first dose, 28.6% ( n = 82) had a PP that was wider than 40 mmHg. After the first dose, 5.2% and 4.9% of the individuals experienced an increase or decrease in SBP, respectively, of more than 20 mmHg. After the second dose, the SBP of 11% ( n = 32) decreased by at least 20 mmHg. Conclusions : Improved understanding of vaccine effects on BP may help address vaccine hesitancy in healthcare workers. more...

Objective: The National Health Service (NHS) produces more carbon emissions than any public sector organisation in England. In 2020, it became the first health service worldwide to commit to becoming carbon net zero, the same year as the COVID-19 pandemic forced healthcare systems globally to rapidly adapt service delivery. As part of this, outpatient appointments became largely remote. Although the environmental benefit of this change may seem intuitive the impact on patient outcomes must remain a priority. Previous studies have evaluated the impact of telemedicine on emission reduction and patient outcomes but never before in the gastroenterology outpatient setting., Method: 2140 appointments from general gastroenterology clinics across 11 Trusts were retrospectively analysed prior to and during the pandemic. 100 consecutive appointments during two periods of time, from 1 June 2019 (prepandemic) to 1 June 2020 (during the pandemic), were used. Patients were telephoned to confirm the mode of transport used to attend their appointment and electronic patient records reviewed to assess did-not-attend (DNA) rates, 90-day admission rates and 90-day mortality rates., Results: Remote consultations greatly reduced the carbon emissions associated with each appointment. Although more patients DNA their remote consultations and doctors more frequently requested follow-up blood tests when reviewing patients face-to-face, there was no significant difference in patient 90-day admissions or mortality when consultations were remote., Conclusion: Teleconsultations can provide patients with a flexible and safe means of being reviewed in outpatient clinics while simultaneously having a major impact on the reduction of carbon emissions created by the NHS., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.) more...

Colonoscopy is the gold standard for early diagnosis and pre-emptive treatment of colorectal cancer by detecting and removing colonic polyps. Deep learning approaches to polyp detection have shown potential for enhancing polyp detection rates. However, the majority of these systems are developed and evaluated on static images from colonoscopies, whilst in clinical practice the treatment is performed on a real-time video feed. Non-curated video data remains a challenge, as it contains low-quality frames when compared to still, selected images often obtained from diagnostic records. Nevertheless, it also embeds temporal information that can be exploited to increase predictions stability. A hybrid 2D/3D convolutional neural network architecture for polyp segmentation is presented in this paper. The network is used to improve polyp detection by encompassing spatial and temporal correlation of the predictions while preserving real-time detections. Extensive experiments show that the hybrid method outperforms a 2D baseline. The proposed architecture is validated on videos from 46 patients and on the publicly available SUN polyp database. A higher performance and increased generalisability indicate that real-world clinical implementations of automated polyp detection can benefit from the hybrid algorithm and the inclusion of temporal information., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: D.S, L.B.L and are involved with Odin Vision Ltd. D.S is involved with Digital Surgery Ltd, (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.) more...

The discovery that biomechanical forces regulate microbial virulence was established with the finding that physiological low fluid shear (LFS) forces altered gene expression, stress responses, and virulence of the enteric pathogen Salmonella enterica serovar Typhimurium during the log phase. These log phase LFS-induced phenotypes were independent of the master stress response regulator, RpoS (σ S ). Given the central importance of RpoS in regulating stationary-phase stress responses of S. Typhimurium cultured under conventional shake flask and static conditions, we examined its role in stationary-phase cultures grown under physiological LFS. We constructed an isogenic rpoS mutant derivative of wild-type S. Typhimurium and compared the ability of these strains to survive in vitro pathogenesis-related stresses that mimic those encountered in the infected host and environment. We also compared the ability of these strains to colonize (adhere, invade, and survive within) human intestinal epithelial cell cultures. Unexpectedly, LFS-induced resistance of stationary-phase S. Typhimurium cultures to acid and bile salts stresses did not rely on RpoS. Likewise, RpoS was dispensable for stationary-phase LFS cultures to adhere to and survive within intestinal epithelial cells. In contrast, the resistance of these cultures to challenges of oxidative and thermal stresses, and their invasion into intestinal epithelial cells was influenced by RpoS. These findings expand our mechanistic understanding of how physiological fluid shear forces modulate stationary-phase S. Typhimurium physiology in unexpected ways and provide clues into microbial mechanobiology and nuances of Salmonella responses to microenvironmental niches in the infected host. IMPORTANCE Bacterial pathogens respond dynamically to a variety of stresses in the infected host, including physical forces of fluid flow (fluid shear) across their surfaces. While pathogens experience wide fluctuations in fluid shear during infection, little is known about how these forces regulate microbial pathogenesis. This is especially important for stationary-phase bacterial growth, which is a critical period to understand microbial resistance, survival, and infection potential, and is regulated in many bacteria by the general stationary-phase stress response protein RpoS. Here, we showed that, unlike conventional culture conditions, several stationary-phase Salmonella pathogenic stress responses were not impacted by RpoS when bacteria were cultured under fluid shear conditions relevant to those encountered in the intestine of the infected host. These findings offer new insight into how physiological fluid shear forces encountered by Salmonella during infection might impact pathogenic responses in unexpected ways that are relevant to their disease-causing ability. more...

Background and Aims: Seattle protocol biopsies for Barrett's Esophagus (BE) surveillance are labour intensive with low compliance. Dysplasia detection rates vary, leading to missed lesions. This can potentially be offset with computer aided detection. We have developed convolutional neural networks (CNNs) to identify areas of dysplasia and where to target biopsy., Methods: 119 Videos were collected in high-definition white light and optical chromoendoscopy with i-scan (Pentax Hoya, Japan) imaging in patients with dysplastic and non-dysplastic BE (NDBE). We trained an indirectly supervised CNN to classify images as dysplastic/non-dysplastic using whole video annotations to minimise selection bias and maximise accuracy. The CNN was trained using 148,936 video frames (31 dysplastic patients, 31 NDBE, two normal esophagus), validated on 25,161 images from 11 patient videos and tested on 264 iscan-1 images from 28 dysplastic and 16 NDBE patients which included expert delineations. To localise targeted biopsies/delineations, a second directly supervised CNN was generated based on expert delineations of 94 dysplastic images from 30 patients. This was tested on 86 i-scan one images from 28 dysplastic patients., Findings: The indirectly supervised CNN achieved a per image sensitivity in the test set of 91%, specificity 79%, area under receiver operator curve of 93% to detect dysplasia. Per-lesion sensitivity was 100%. Mean assessment speed was 48 frames per second (fps). 97% of targeted biopsy predictions matched expert and histological assessment at 56 fps. The artificial intelligence system performed better than six endoscopists., Interpretation: Our CNNs classify and localise dysplastic Barrett's Esophagus potentially supporting endoscopists during surveillance., (© 2022 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.) more...

Objectives: There is uncertainty regarding the efficacy of artificial intelligence (AI) software to detect advanced subtle neoplasia, particularly flat lesions and sessile serrated lesions (SSLs), due to low prevalence in testing datasets and prospective trials. This has been highlighted as a top research priority for the field., Methods: An AI algorithm was evaluated on four video test datasets containing 173 polyps (35,114 polyp-positive frames and 634,988 polyp-negative frames) specifically enriched with flat lesions and SSLs, including a challenging dataset containing subtle advanced neoplasia. The challenging dataset was also evaluated by eight endoscopists (four independent, four trainees, according to the Joint Advisory Group on gastrointestinal endoscopy [JAG] standards in the UK)., Results: In the first two video datasets, the algorithm achieved per-polyp sensitivities of 100% and 98.9%. Per-frame sensitivities were 84.1% and 85.2%. In the subtle dataset, the algorithm detected a significantly higher number of polyps (P < 0.0001), compared to JAG-independent and trainee endoscopists, achieving per-polyp sensitivities of 79.5%, 37.2% and 11.5%, respectively. Furthermore, when considering subtle polyps detected by both the algorithm and at least one endoscopist, the AI detected polyps significantly faster on average., Conclusions: The AI based algorithm achieved high per-polyp sensitivities for advanced colorectal neoplasia, including flat lesions and SSLs, outperforming both JAG independent and trainees on a very challenging dataset containing subtle lesions that could have been overlooked easily and contribute to interval colorectal cancer. Further prospective trials should evaluate AI to detect subtle advanced neoplasia in higher risk populations for colorectal cancer., (© 2021 The Authors. Digestive Endoscopy published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.) more...

Background: The Baveno VI consensus identifies patients with compensated advanced chronic liver disease (cACLD) who can safely avoid screening endoscopy. However, concordance in clinical practice with this guidance is unknown. We audited clinical practice and the provision of transient elastography (TE) aiming to identify potential cost savings and benefits., Methods: Retrospective data collection from 12 sites across London over 6 months by reviewing oesophagogastroduodenoscopy (OGD) reports, platelet count and TE results as well as information on site-specific provision of TE., Results: Three-hundred and fifty-one screening procedures were identified; 177 (50.43%) had a TE test performed within the preceding 12 months; 142 (80.23%) patients with a recent TE test did not meet criteria for screening OGD. TE provision varied widely between sites., Conclusion: Improving concordance with the Baveno criteria through improved provision of TE would have benefits for patients, healthcare systems and the environment and would help to address the challenges of moving on from the COVID-19 pandemic., (© Royal College of Physicians 2022. All rights reserved.) more...

Background and Aims: With the potential integration of artificial intelligence (AI) into clinical practice, it is essential to understand end users' perception of this novel technology. The aim of this study, which was endorsed by the British Society of Gastroenterology (BSG), was to evaluate the UK gastroenterology and endoscopy communities' views on AI., Methods: An online survey was developed and disseminated to gastroenterologists and endoscopists across the UK., Results: One hundred four participants completed the survey. Quality improvement in endoscopy (97%) and better endoscopic diagnosis (92%) were perceived as the most beneficial applications of AI to clinical practice. The most significant challenges were accountability for incorrect diagnoses (85%) and potential bias of algorithms (82%). A lack of guidelines (92%) was identified as the greatest barrier to adopting AI in routine clinical practice. Participants identified real-time endoscopic image diagnosis (95%) as a research priority for AI, while the most perceived significant barriers to AI research were funding (82%) and the availability of annotated data (76%). Participants consider the priorities for the BSG AI Task Force to be identifying research priorities (96%), guidelines for adopting AI devices in clinical practice (93%) and supporting the delivery of multicentre clinical trials (91%)., Conclusion: This survey has identified views from the UK gastroenterology and endoscopy community regarding AI in clinical practice and research, and identified priorities for the newly formed BSG AI Task Force., Competing Interests: Competing interests: RK, RFB, OFA, NP, GC and SD declared no competing interests. MH received speaker fees from Cook Medical. DS is a shareholder in Odin Vision and Digital Surgery. LBL is a consultant and minor shareholder in Odin Vision. He has received research grants from Medtronic, Pentax Medical and DynamX; he is also on the advisory board for DynamX and Ninepoint Medical., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.) more...

Oral administration of medications to children requires age-appropriate dosage forms and strengths. In this study, we: (i) assessed the extent of oral dosage form manipulations, (ii) documented how it is carried out, and (iii) examined the attitudes and sources of information regarding the handling from healthcare professionals. Prospective reviews of electronic records, ward observations, and clinician surveys were performed at a paediatric neurology ward and a paediatric oncology ward in Sweden during April to May of 2018. Approximately 15% of oral medications were manipulated for the studied patient group (median age 12.9 years in oncology, 5.8 years in neurology) with approximately 30% of the patients having an enteral feeding tube. Manipulations were performed both to obtain an appropriate dose from, for example, a fraction of the original tablet or to obtain a powder that could be used to prepare a slurry for administration through enteral feeding tubes. Risks identified were related to patient safety such as cross contamination, suboptimal absorption/pharmacokinetics and inaccurate dose. When examining the working environment of nurses, we observed safe handling of hazardous substances but the nurses occasionally experienced stress and a fear of making mistakes due to absence of information. Paediatricians experienced a lack of time to search for proper information on manipulations. As a step towards improving safety in paediatric medication, we suggest the introduction of clinical pharmacists into the team and further evaluating the possibilities of using more ready-to-administer medications with necessary product information and pharmacovigilance support. more...

Colonoscopy remains the gold standard investigation for colorectal cancer screening as it offers the opportunity to both detect and resect pre-malignant and neoplastic polyps. Although technologies for image-enhanced endoscopy are widely available, optical diagnosis has not been incorporated into routine clinical practice, mainly due to significant inter-operator variability. In recent years, there has been a growing number of studies demonstrating the potential of convolutional neural networks (CNN) to enhance optical diagnosis of polyps. Data suggest that the use of CNNs might mitigate the inter-operator variability amongst endoscopists, potentially enabling a "resect and discard" or "leave in" strategy to be adopted in real-time. This would have significant financial benefits for healthcare systems, avoid unnecessary polypectomies of non-neoplastic polyps and improve the efficiency of colonoscopy. Here, we review advances in CNN for the optical diagnosis of colorectal polyps, current limitations and future directions., Competing Interests: Conflict-of-interest statement: Rawen Kader is supported by the Wellcome/EPSRC Centre for Interventional and Surgical Sciences (WEISS) at UCL; [203145Z/16/Z]. Danail Stoyanov owns shares in Odin Vision and Digital Surgery Ltd. Laurence B Lovat owns shares in Odin Vision. The remaining authors declare no conflict of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.) more...

(1) Background: Alveolar echinococcosis (AE) is restricted to the northern hemisphere with high endemic regions in Central Europe, North and Central Asia as well as Western China. The larval stage of Echinococcus multilocularis (E. multilocularis) causes AE with tumor-like growth. Humans are accidental hosts. This report is on the first case of AE becoming clinically manifested in the parotic gland. (2) Case presentation: A 52-year-old male patient presented with progressive and painful swelling of the right parotid gland persisting for one year. We performed a partial parotidectomy. The histological examination and immunohistological staining revealed larval stage of E. multilocularis . (3) Conclusion: E. multilocularis is known to infect animals and humans coincidentally, and leads to AE. It is one of the most life-threatening zoonoses in Europe. It typically manifests in the liver (50-77%), with further spreading to other organs being a rare phenomenon. Echinococcosis should be considered in the differential diagnosis of lesions of the parotid gland in endemic areas, but AE has not been described so far in the parotid gland as the sole manifestation and, therefore, impedes the correct diagnosis. A complete resection should be the aim, however, preservation of the facial nerve and adjuvant albendazole therapy is mandatory. more...

Online learning has been present since the early days of the Internet. As with any new technology, users look to make their life easier and to save time. Experts in medical education are no different than other users. They want to adapt new technologies to their fullest. Medical educators have been challenged with keeping education interesting and up to date, while maximizing their resources. The challenges with any online educational program include being able to reach large numbers of learners, having content that is relevant and timely, and having it available thorough many different formats to suit the user. There are many examples of online learning programs in all fields of medicine and many specific to Allergy/Immunology. In this review, we describe a form of real-time videoconferencing referred to as Conferences On-Line Allergy (COLA), which was developed at Children's Mercy Hospital and Clinics. This program, which started as a once a month webinar, has transformed into a well-known curriculum used by many Allergy/Immunology training programs across the United States. It provides not only live interactive conferences but also a library of recorded lectures and workshops that can be used at the learner's convenience. Taking advantage of the generosity of many volunteer presenters, it allows sharing of resources and provides benefits to the Allergy/Immunology community., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.) more...

Contrast-enhanced echocardiography or cardiac magnetic resonance imaging is of value in the diagnosis of apical hypertrophic cardiomyopathy. Apical hypertrophic cardiomyopathy is rare in Caucasians, and gene negativity does not rule out the diagnosis. Risk stratification for sudden cardiac death and decisions about anticoagulation in cases with atrial fibrillation should be based on guidelines., Competing Interests: Dr Magnusson received an unrestricted research grant from Abbott and speakers fee from Alnylam, Bayer, Boehringer‐Ingelheim, Pfizer, and Novo Nordisk. more...

The inability of central nervous system (CNS) to regenerate following traumatic brain injury (TBI) can be attributed to apoptotic cell death, inhibitory extrinsic environment, and the limited ability of neurons to regenerate. Thus, fostering the intrinsic regenerative potential and minimizing neuronal cell death could be a promising therapeutic approach. Pyrroloquinoline quinone (PQQ) was previously reported for its neuroprotective and regenerative potential on peripheral nerves. Here, we investigated the ability of PQQ to induce neurite re-growth in a wound healing model on cultured cerebellar granular neurons (CGNs), an integral part of cerebellar circuitry, as one of the most affected areas following TBI. The neuroprotective effect was also examined utilizing K + /FCS deprivation-induced apoptosis model in CGNs. Resveratrol (RVT), an effective promoter of neuroprotection and regeneration both centrally and peripherally was also investigated separately and in combination with PQQ to establish a possible synergistic effect. RVT (5 μM) and PQQ (0.5 μM) showed a tendency to promote neurite re-growth in the wound healing assay, however the effect observed was statistically insignificant. Higher concentrations of PQQ (1 and 2 μM) were found to be less effective. Resveratrol did not affect neurite length in CGNs culture; however, it did significantly increase the number of viable CGNs. For the neuroprotective effect; PQQ and RVT showed a significant increase in the survival of CGNs following K + /FCS deprivation of culture. Thus, both compounds showed a tendency to support neurite outgrowth in addition to a significant neuroprotective effect, but no synergistic effect was detected., (Copyright © 2018 Elsevier B.V. All rights reserved.) more...

Purpose of Review: The use of environmental interventions to improve outcomes in asthmatics has long been an elusive goal. While numerous interventions have been studied, the results of clinical trials have been mixed. This review aims to identify combinations of interventions that have been proven to be effective and to propose a model for using them in a clinical setting., Recent Findings: An NIH workshop emphasized a need for research to identify effective interventions for reducing indoor exposures and improving asthma outcomes. A number of innovative measures were described, though evidence supporting their use was lacking. A recent systematic review described various interventions for which evidence is available. The greatest challenge for this approach is the same as that for the medical approach to treatment: nonadherence. Given evidence for effective interventions, control of environmental exposures should lead to improved asthma outcomes. Methods to improve adherence need to be identified. more...

The objective of this study was to understand the impact of hazardous and harmful use of alcohol and/or other drugs on ARV adherence and disease progression among HIV patients. A cross-sectional study design was used. A total of 1503 patients attending HIV clinics in Cape Town, South Africa were screened for problematic substance use. A sub-sample of 607 patients (303 patients who screened positive for problematic substance use and 304 who did not) participated in this study. Hazardous or harmful alcohol use and problematic drug use predicted missing and stopping ARVs which, in turn, was associated with a decrease in CD4 counts and more rapid HIV-disease progression and poorer health outcomes in people living with HIV/AIDS (PLWHA). The findings of this study underscore the need for an integrated approach to managing substance-use disorders in PLWHA. more...

History and Clinical Findings: A 67-year-old woman with a history of chronic obstructive pulmonary disease and breast cancer developed an increase in size and number of pulmonary nodules that had previously been stable over the course of 9 years., Investigations: Thoracic computed tomography revealed a well-defined pulmonary lesion with a diameter of 1,1 × 1,1 cm, accompanied by multiple bilateral pulmonary nodules with a maximum size of 5 mm. Thoracoscopic resection of the major nodule was extended to a completive resection of an adjacent lung area that operatively showed a macroscopically noticeable hypervascularity. Histopathological examination assigned the larger lesion to a typical carcinoid; the additionally resected hypervascular lung parenchyma confirmed an accumulation of hyperplastic neuroendocrine cells in terms of a diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH)., Treatment and Course: Since histological examination showed an entirely resected neuroendocrine tumor classified as typical carcinoid, and considering DIPNECH to be a preinvasive lesion, the therapeutic management consisted of serial imaging by computed tomography. During the last two years, no progression of either the pulmonary lesions or of the obstructive disease was observed., Conclusion: DIPNECH is a rare, primary pulmonary process with proliferation of hyperplastic neuroendocrine cells, affecting principally middle-aged, non-smoking women. It is considered to be a precursor lesion to pulmonary carcinoid tumors. Given its only minor risk of invasive metastatic spread, serial imaging for timely detection of progressing lesions and optimizing of concomitant obstructive pulmonary disease are the preferred treatment approaches., (© Georg Thieme Verlag KG Stuttgart · New York.) more...

Background: A performance measurement system is planned for South African substance abuse treatment services. Provider-level barriers to implementing these systems have been identified in the United States, but little is known about the nature of these barriers in South Africa. This study explored the willingness of South African substance abuse treatment providers' to adopt a performance measurement system and perceived barriers to monitoring service quality that would need to be addressed during system development., Methods: Three focus group discussions were held with treatment providers from two of the nine provinces in South Africa. These providers represented the diverse spread of substance abuse treatment services available in the country. The final sample comprised 21 representatives from 12 treatment facilities: eight treatment centres in the Western Cape and four in KwaZulu-Natal. Content analysis was used to extract core themes from these discussions., Results: Participants identified barriers to the monitoring of service quality that included outdated modes of collecting data, personnel who were already burdened by paperwork, lack of time to collect data, and limited skills to analyse and interpret data. Participants recommended that developers engage with service providers in a participatory manner to ensure that service providers are invested in the proposed performance measurement system., Conclusion: Findings show that substance abuse treatment providers are willing to adopt a performance measurement system and highlight several barriers that need to be addressed during system development in order to enhance the likelihood that this system will be successfully implemented. more...

The aging brain suffers mitochondrial dysfunction and a reduced availability of energy in the form of ATP, which in turn may cause or promote the decline in cognitive, sensory, and motor function observed with advancing age. There is a need for animal models that display some of the pathological features of human brain aging in order to study their prevention by e.g. dietary factors. We thus investigated the suitability of the fast-aging senescence-accelerated mouse-prone 8 (SAMP8) strain and its normally aging control senescence-accelerated mouse-resistant 1 (SAMR1) as a model for the age-dependent changes in mitochondrial function in the brain. To this end, 2-months old male SAMR1 (n=10) and SAMP8 mice (n=7) were fed a Western type diet (control groups) for 5months and one group of SAMP8 mice (n=6) was fed an identical diet fortified with 500mg curcumin per kg. Dissociated brain cells and brain tissue homogenates were analyzed for malondialdehyde, heme oxygenase-1 mRNA, mitochondrial membrane potential (MMP), ATP concentrations, protein levels of mitochondrial marker proteins for mitochondrial membranes (TIMM, TOMM), the mitochondrial permeability transition pore (ANT1, VDAC1, TSPO), respiration complexes, and fission and fusion (Fis, Opa1, Mfn1, Drp1). Dissociated brain cells isolated from SAMP8 mice showed significantly reduced MMP and ATP levels, probably due to significantly diminished complex V protein expression, and increased expression of TSPO. Fission and fusion marker proteins indicate enhanced mitochondrial fission in brains of SAMP8 mice. Treatment of SAMP8 mice with curcumin improved MMP and ATP and restored mitochondrial fusion, probably by up-regulating nuclear factor PGC1α protein expression. In conclusion, SAMP8 compared to SAMR1 mice are a suitable model to study age-dependent changes in mitochondrial function and curcumin emerges as a promising nutraceutical for the prevention of neurodegenerative diseases that are accompanied or caused by mitochondrial dysfunction., (Copyright © 2013 Elsevier Ltd. All rights reserved.) more...

Objective: This study aimed to determine a demographic profile of methamphetamine (MA)-related admissions to major psychiatric services in Cape Town, obtain a substance use profile from admitted patients, a profile of common MA-related symptoms encountered during the assessment of the patients presenting with MA-related problems, and a brief profile of the psychiatric diagnoses made., Method: Staff in six psychiatric hospitals or wards in Cape Town collected data on methamphetamine related admissions between July and December 2008 using a one-page record review form. The data collection form consisted of the patient's demographic details, presenting symptoms, previous admission details, current MA and other substance use information, and DSM-IV diagnosis., Results: A total of 235 forms were completed. Most patients were male (69%) and the mean age was 25 years. The most common presenting symptoms were aggressive behaviour (74%), followed by delusions (59%) and hallucinations (57%). Males were two times more likely to present with aggression as compared to females, while females were significantly more likely to present with depressed mood or euphoric/elevated mood. The majority of patients had substance-induced psychotic disorder (41%), followed by schizophrenia (31%). Twelve percent (12%) had bipolar mood disorder., Conclusion: MA-related psychiatric admissions pose serious challenges to all health services dealing with these patients. Further training and treatment protocol development and distribution is indicated. more...

Objective: There is growing concern about the effect of substance use on HIV treatment outcomes. The study objectives included: (i) evaluating whether the use of validated questionnaires (AUDIT and DUDIT) provide useful and consistent information of alcohol and drug consumption when compared with the use of biomarkers of alcohol in (urine and hair) and drugs in (urine) and (ii) assessing the feasibility of using self-report measures compared with urine and hair tests., Method: Participants were HIV positive patients attending an HIV community health clinic in Kraaifontein, Cape Town. Hair and urine samples were collected and analysed for alcohol, in Fatty Acid Ethyl Esters (FAEE) and in Ethyl Glucuronide and (EtG), and drugs. Biological markers were compared with self-report measures of alcohol and drug consumption in terms of sensitivity, specificity. Forty-three participants completed the self-report measures, while 30 provided hair and urine samples., Results: On the AUDIT, 18 (41.9%) participants screened positive for harmful and hazardous drinking and 13 (30.2%) participants on the DUDIT screened positive for having a drug-related problem. Two of 30 participants (7%) tested positive for alcohol abuse on FAEE analysis. For EtG, 6 of 24 (25%) participants tested positive for alcohol abuse. On hair drug analysis, all 30 participants tested negative for cannabis, amphetamines, opiates, cocaine, PCP and methaqualone. On the urinalysis, 1 of 30 participants tested positive for cannabis and everyone tested negative for all other drugs included in the screening., Conclusion: Substance use among patients attending HIV clinics appears to be a problem, especially alcohol. Self-report measures seem to be a more cost effective option for screening of alcohol and drug abuse in resource poor settings. more...

Tuberculosis remains a global health threat, and there is dire need to develop a vaccine that is safe and efficacious and confers long-lasting protection. In this study, we constructed recombinant attenuated Salmonella vaccine (RASV) strains with plasmids expressing fusion proteins consisting of the 80 amino-terminal amino acids of the type 3 secretion system effector SopE of Salmonella and the Mycobacterium tuberculosis antigens early secreted antigenic target 6-kDa (ESAT-6) protein and culture filtrate protein 10 (CFP-10). We demonstrated that the SopE-mycobacterial antigen fusion proteins were translocated into the cytoplasm of INT-407 cells in cell culture assays. Oral immunization of mice with RASV strains synthesizing SopE-ESAT-6-CFP-10 fusion proteins resulted in significant protection of the mice against aerosol challenge with M. tuberculosis H37Rv that was similar to the protection afforded by immunization with Mycobacterium bovis bacillus Calmette-Guérin (BCG) administered subcutaneously. In addition, oral immunization with the RASV strains specifying these mycobacterial antigens elicited production of significant antibody titers to ESAT-6 and production of ESAT-6- or CFP-10-specific gamma interferon (IFN-γ)-secreting and tumor necrosis factor alpha (TNF-α)-secreting splenocytes. more...