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Detection of dynorphin 1-17 biotransformation fragments in human nasal polyps by UPLC-QTOF-MS

Ballouze R, Ismail MN, Abu Kassim NS, Salhimi SM, Mohamad I, Abd Mutalib NS, et al.

Anal Bioanal Chem, 2024 Jan;416(2):545-557.
PMID: 38040942 DOI: 10.1007/s00216-023-05061-3

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a persistent inflammation of the sinonasal mucosa. CRSwNP treatments are associated with inconsistent efficacy and recurrence of symptoms. Dynorphin 1-17 (DYN 1-17) and its fragments have been shown to modulate the immune response in various inflammatory conditions. This study aimed to investigate the effect of different pH and degrees of inflammation on DYN 1-17 metabolism in human CRSwNP tissues. DYN 1-17 was incubated with grade 3 and grade 4 inflamed tissues of CRSwNP patients at pH 5.5 and pH 7.4 over a range of incubation periods. The resulting fragments were identified using an ultra-performance liquid chromatography (UPLC) system coupled to quadrupole-time of flight (QTOF) mass spectrometry based on their accurate mass. The rate of DYN 1-17 fragmentation was slower at pH 5.5 in comparison to pH 7.4. The extent and rate of metabolism of DYN 1-17 were much lower in grade 3 inflamed tissue (31-32 fragments) than in grade 4 (34-41 fragments). N-Terminal fragments (DYN 1-15, 1-11, 1-10, and 1-6) were metabolized slower at pH 5.5 as compared to pH 7.4. DYN 1-12, 1-8, 2-10, 4-10, 5-10, and 8-14 were only observed under the inflammatory pH while DYN 5-17 and 6-17 were only identified upon incubation with grade 4 CRSwNP tissues. DYN 1-17 metabolism was significantly affected by the pH level and the severity of the inflammation of CRSwNP tissues, indicating the potential roles of DYN 1-17 and its fragments in modulating the inflammatory response and their avenue as therapeutics in future studies.
Fulltext Sustainable Medical Teaching and Learning During the COVID-19 Pandemic: Surviving the New Normal

Yusoff MSB, Hadie SNH, Mohamad I, Draman N, Muhd Al-Aarifin I, Wan Abdul Rahman WF, et al.

Malays J Med Sci, 2020 May;27(3):137-142.
PMID: 32684814 MyJurnal DOI: 10.21315/mjms2020.27.3.14

During the first phase of the Movement Control Order, many medical lecturers had difficulty adapting to the online teaching and learning methods that were made compulsory by the institutional directives. Some of these lecturers are clinicians who need to juggle between clinical work and teaching, and consider a two-week adaptation during this period to be not enough. Furthermore, converting traditional face-to-face learning to online formats for undergraduate and postgraduate clinical programmes would reduce the learning outcomes, especially those related to clinical applications and the acquisition of new skills. This editorial discusses the impact that movement restrictions have had on medical teaching and learning, the alternatives and challenges and the way forward.
Fulltext A measles IgM rapid diagnostic test to address challenges with national measles surveillance and response in Malaysia

Senin A, Noordin NM, Sani JAM, Mahat D, Donadel M, Scobie HM, et al.

PLoS One, 2024;19(3):e0298730.
PMID: 38483868 DOI: 10.1371/journal.pone.0298730

INTRODUCTION: A lateral flow rapid diagnostic test (RDT) enables detection of measles specific immunoglobulin M (IgM) antibody in serum, capillary blood, and oral fluid with accuracy consistent with enzyme immunoassay (EIA). The objectives of the study were: 1) to assess measles RDT inter-reader agreement between two clinic staff; 2) to assess the sensitivity and specificity of the measles RDT relative to standard surveillance testing in a low transmission setting; 3) to evaluate the knowledge, attitudes, and practices of staff in clinics using the RDT; and 4) to assess the impact of RDT testing on the measles public health response in Malaysia.
MATERIALS AND METHODS: The clinic-based prospective evaluation included all suspected measles cases captured by routine measles surveillance at 34 purposely selected clinics in 15 health districts in Malaysia between September 2019 and June 2020, following day-long regional trainings on RDT use. Following informed consent, four specimens were collected from each suspected case, including those routinely collected for standard surveillance [serum for EIA and throat swabs for quantitative reverse transcriptase polymerase chain reaction (RT-qPCR)] together with capillary blood and oral fluid tested with RDTs during the study. RDT impact was evaluated by comparing the rapidity of measles public health response between the pre-RDT implementation (December 2018 to August 2019) and RDT implementation periods (September 2019 to June 2020). To assess knowledge, attitudes, and practices of RDT use, staff involved in the public health management of measles at the selected sites were surveyed.
RESULTS: Among the 436 suspect cases, agreement of direct visual readings of measles RDT devices between two health clinic staff was 99% for capillary blood (k = 0.94) and 97% for oral fluid (k = 0.90) specimens. Of the total, 45 (10%) were positive by measles IgM EIA (n = 44, including five also positive by RT-qPCR) or RT-qPCR only (n = 1), and 38 were positive by RDT (using either capillary blood or oral fluid). Using measles IgM EIA or RT-qPCR as reference, RDT sensitivity using capillary blood was 43% (95% CI: 30%-58%) and specificity was 98% (95% CI: 96%-99%); using oral fluid, sensitivity (26%, 95% CI: 15%-40%) and specificity (97%, 95% CI: 94%-98%) were lower. Nine months after training, RDT knowledge was high among staff involved with the public health management of measles (average quiz score of 80%) and was highest among those who received formal training (88%), followed by those trained during supervisory visits (83%). During the RDT implementation period, the number of days from case confirmation until initiation of public response decreased by about 5 days.
CONCLUSION: The measles IgM RDT shows >95% inter-reader agreement, high retention of RDT knowledge, and a more rapid public health response. However, despite ≥95% RDT specificity using capillary blood or oral fluid, RDT sensitivity was <45%. Higher-powered studies using highly specific IgM assays and systematic RT-qPCR for case confirmation are needed to establish the role of RDT in measles elimination settings.
Fulltext Undiagnosed chicken meat aspiration as a cause of difficult-to-ventilate in a boy with traumatic brain injury

Mohd Ariff NA, Mazlan MZ, Mat Hassan ME, Seevaunnamtum PA, Wan Muhd Shukeri WF, Nik Mohamad NA, et al.

Respir Med Case Rep, 2018;23:93-95.
PMID: 29387523 DOI: 10.1016/j.rmcr.2018.01.001

Introduction: Bronchoscopy is a commonly used procedure in the context of aspiration in the Intensive Care Unit setting. Despite its ability to remove mucus plug and undigested gastric contents, aspiration of gastric content into the trachea is one of the most feared complications among anesthesiologist.
Discussion: The scenario is made worst if the aspiration causes acute hypoxemic respiratory failure immediately post intubation. However, in the event of desaturation, the quick decision to proceed with bronchoscopy is a challenging task to the anesthesiologist without knowing the causes.
Case presentation: We present a case of a 12-year-old boy who had a difficult-to-ventilate scenario post transferring and immediately connected to ventilator in operation theatre (OT) from portable ventilator from the emergency department. She was successfully managed by bronchoscopy.
Conclusion: Special attention should be given to the difficult-to-ventilate scenario post intubation of traumatic brain injury patient prior to operation. Prompt diagnosis and bronchoscope-assisted removal of foreign body was found to be a successful to reduce morbidity and mortality.
Fulltext ARCHERY: a prospective observational study of artificial intelligence-based radiotherapy treatment planning for cervical, head and neck and prostate cancer - study protocol

Aggarwal A, Court LE, Hoskin P, Jacques I, Kroiss M, Laskar S, et al.

BMJ Open, 2023 Dec 07;13(12):e077253.
PMID: 38149419 DOI: 10.1136/bmjopen-2023-077253

INTRODUCTION: Fifty per cent of patients with cancer require radiotherapy during their disease course, however, only 10%-40% of patients in low-income and middle-income countries (LMICs) have access to it. A shortfall in specialised workforce has been identified as the most significant barrier to expanding radiotherapy capacity. Artificial intelligence (AI)-based software has been developed to automate both the delineation of anatomical target structures and the definition of the position, size and shape of the radiation beams. Proposed advantages include improved treatment accuracy, as well as a reduction in the time (from weeks to minutes) and human resources needed to deliver radiotherapy.
METHODS: ARCHERY is a non-randomised prospective study to evaluate the quality and economic impact of AI-based automated radiotherapy treatment planning for cervical, head and neck, and prostate cancers, which are endemic in LMICs, and for which radiotherapy is the primary curative treatment modality. The sample size of 990 patients (330 for each cancer type) has been calculated based on an estimated 95% treatment plan acceptability rate. Time and cost savings will be analysed as secondary outcome measures using the time-driven activity-based costing model. The 48-month study will take place in six public sector cancer hospitals in India (n=2), Jordan (n=1), Malaysia (n=1) and South Africa (n=2) to support implementation of the software in LMICs.
ETHICS AND DISSEMINATION: The study has received ethical approval from University College London (UCL) and each of the six study sites. If the study objectives are met, the AI-based software will be offered as a not-for-profit web service to public sector state hospitals in LMICs to support expansion of high quality radiotherapy capacity, improving access to and affordability of this key modality of cancer cure and control. Public and policy engagement plans will involve patients as key partners.