Clinical characteristics and predictors of mortality in patients with melioidosis: the Kapit experience.

OBJECTIVES: Melioidosis, caused by Burkholderia pseudomallei, is prevalent in rural areas of Malaysia. The aim of this study is to delineate the epidemiology and predictors of mortality from melioidosis in Kapit district, Sarawak. METHODS: For this retrospective study of patients with culture-confirmed melioidosis admitted to Kapit Hospital, Sarawak, Malaysia, between July 2016 and July 2019, epidemiological, clinical and microbiological data were obtained. Univariate and multivariate logistic regression analyses were used to determine predictors of mortality. RESULTS: Seventy three patients met inclusion criteria. Diabetes mellitus (28.8%) and hypertension (27.4%) were primary co-morbidities. Clinical spectrum of melioidosis ranged from bacteraemia (64.4%), pneumonia (61.6%) and internal organ abscesses (49.3%) to localised soft tissue (21.9%) and joint abscesses (6.9%). Mortality rate was 12.3%. Bacteraemia and pneumonia were significantly associated with septic shock, whereas patients with soft tissue abscesses tended to present with a milder form of melioidosis without septic shock. Septic shock, mechanical ventilation, intensive care unit admission, serum urea, creatinine, bicarbonate, albumin and aspartate transaminase were all significantly associated with increased mortality on univariate analysis (all P < 0.05). Multivariate analysis revealed that low serum bicarbonate (P = 0.004, OR 0.64, 95% CI 0.48-0.87) and albumin (P = 0.031, OR 0.73, 95% CI 0.54-0.97) could be associated with a higher mortality. CONCLUSION: Melioidosis remains a fatal infection and commonly presents with septic shock, in the form of bacteraemia and pneumonia. Two routine clinical parameters, serum bicarbonate and serum albumin, may have important prognostic implications in septicaemic melioidosis.

Clinical and radiological characteristics of mediastinal melioidosis: A four-year retrospective cohort from Sabah, Malaysia.

BACKGROUND: Melioidosis is a potentially fatal tropical infection. Little is known about mediastinal involvement in melioidosis. This study aimed to (a) describe the prevalence and demographics of various morphologies of mediastinal melioidosis, (b) propose a classification for radiological morphologies of mediastinal melioidosis. METHODS: A retrospective cohort study was performed. Case records of consecutive patients with culture-positive melioidosis who underwent computed tomography (CT) thorax from January 1, 2018-February 28, 2022, were reviewed. RESULTS: 486 culture-positive melioidosis patients were identified, of which 70 underwent CT thorax. 41 patients demonstrating mediastinal involvement were included in the final analysis, of which four were mediastinal collections, while the rest were classified into those with necrotic or matted appearances, and subcentimeter and larger than 1 cm. Culture-positivity was proven from blood in 83 % of patients (n = 34), with the remaining from chest wall pus, neck abscess pus, sputum, liver abscess, seminal vesicle, pleural, pericardial and peritoneal fluid. The most commonly associated pulmonary manifestations were consolidation and pleural effusion. Half had diabetes; a quarter had chronic kidney disease, while one had syphilis. Exposure to soil was present in six patients: quarry (n = 1), construction (n = 2), farmer (n = 1), living environment (n = 2). Seven patients succumbed before the end of 6-week intensive phase antibiotic treatment. CONCLUSION: Mediastinal melioidosis is a spectrum with multiple overlapping features consisting of necrosis, matted lymph nodes, multiseptated and non-septated collections. Further studies will elucidate the prognostic implications of mediastinal melioidosis.

COVID-19 breakthrough infections and humoral immune response among BNT162b2 vaccinated healthcare workers in Malaysia.

The evaluation of breakthrough infection and humoral immunity responses are important outcomes for vaccination policy for healthcare staff. This prospective cohort study collected blood samples at 5-time points; before primary vaccine doses, and at 2, 10 and 24 weeks after BNT162b2 vaccination from 551 HCWs, between March and October 2021. We investigated the association between anti-spike-1 protein receptor-binding domain (anti-S1-RBD) antibody geometric mean titre (GMT) and breakthrough infections. Two weeks post-vaccination, the GMT of anti-S1-RBD antibodies was measured at almost maximum detectable value (3115 BAU/ml [95% CI, 3051-3180]); it decreased to 1486 BAU/ml (95% CI, 1371-1610) at 10 weeks; and to 315 BAU/ml (95% CI, 283-349) at 24 weeks. Prior COVID-19 infection and age significantly affected the antibody titres. Fifty-six participants, none of whom were COVID-19 convalescents, had breakthrough infections between 10 and 24 weeks post-vaccination. Before breakthrough infections, the GMT was not different between the breakthrough and non-breakthrough individuals. After infection, the GMT was significantly higher in individuals with breakthrough infections (2038 BAU/ml [95%CI, 1547-2685]), specifically in symptomatic breakthroughs, compared to those without infection (254 BAU/ml [95%CI, 233-278]). A notable surge in breakthrough infections among healthcare workers coincided with the emergence of the Delta variant and when BNT162b2-elicited antibody responses waned in 10-24 weeks (i.e. approximately 3-6 months). Post-breakthrough, the antibody response was boosted in individuals with symptomatic presentations, but not asymptomatic individuals. The study finding supports administering booster vaccination for healthcare staff, including those who recovered from asymptomatic breakthrough infection.

Increased Theta Oscillations During Motor Imagery in a Subject with Late-stage ALS.

Non-invasive brain computer interface (BCI) has been successfully used to control cursors, helicopters and robotic arms. However, this technology is not widely adopted by people with late-stage amyotrophic lateral sclerosis (ALS) due to poor effectiveness. In this study, we attempt to assess the cognitive state of a completely locked-in ALS subject, and her ability to use motor imagery-based BCI for control. The subject achieves above chance level accuracies for both open loop (62.2%) and closed-loop (68.7%) 2-class movement vs. idle decoding. We also observe a prominent theta oscillation with peak frequency at 4.5 Hz during the experiments. Quantification shows that the theta oscillatory power increases during motor imagery tasks compared to idle tasks for both open-loop as well as closed-loop BCI tasks. Furthermore, for closed-loop sessions, theta oscillation power correlates positively with feedback accuracy during movement tasks, and negatively with feedback accuracy during idle tasks. Our study demonstrates the feasibility of motor imagery-based BCI for late-stage ALS subjects, and highlights the importance of feedback during BCI implementation.

EEG Channel Selection Based on Correlation Coefficient for Motor Imagery Classification: A Study on Healthy Subjects and ALS Patient.

Brain-Computer Interface (BCI) provides an alternate channel of interaction for people with severe motor disabilities. The Common Spatial Pattern (CSP) algorithm is effective in extracting discriminative features from EEG data for motor imagery-based Brain-Computer Interface (BCI). CSP yields signal from various locations for better performance. In this study, we selected a subset of EEG channels using correlation coefficient of spectral entropy and compared the classification performance using the Filter Bank Common Spatial Pattern (FBCSP) algorithm. We conducted experiments on 4 healthy subjects and one Amyotrophic Lateral Sclerosis (ALS) patient. The results showed that the proposed channel selection method increased classification accuracy of all subjects from 1.25% to 8.22%. Optimal performance was obtained using between 13 to 24 channels, and channels located over the motor cortex zone possess higher probabilities of being selected. Comparing with the channels manually selected to over the motor cortex area, the correlation coefficient method is able to identify the optimal channel combination and improve the motor imagery decoding accuracy of Healthy and ALS subjects.

Overexpression of the microRNA miR-433 promotes resistance to paclitaxel through the induction of cellular senescence in ovarian cancer cells.

Annually, ovarian cancer (OC) affects 240,000 women worldwide and is the most lethal gynecological malignancy. High-grade serous OC (HGSOC) is the most common and aggressive OC subtype, characterized by widespread genome changes and chromosomal instability and is consequently poorly responsive to chemotherapy treatment. The objective of this study was to investigate the role of the microRNA miR-433 in the cellular response of OC cells to paclitaxel treatment. We show that stable miR-433 expression in A2780 OC cells results in the induction of cellular senescence demonstrated by morphological changes, downregulation of phosphorylated retinoblastoma (p-Rb), and an increase in ß-galactosidase activity. Furthermore, in silico analysis identified four possible miR-433 target genes associated with cellular senescence: cyclin-dependent kinase 6 (CDK6), MAPK14, E2F3, and CDKN2A. Mechanistically, we demonstrate that downregulation of p-Rb is attributable to a miR-433-dependent downregulation of CDK6, establishing it as a novel miR-433 associated gene. Interestingly, we show that high miR-433 expressing cells release miR-433 into the growth media via exosomes which in turn can induce a senescence bystander effect. Furthermore, in relation to a chemotherapeutic response, quantitative real-time polymerase chain reaction (qRT-PCR) analysis revealed that only PEO1 and PEO4 OC cells with the highest miR-433 expression survive paclitaxel treatment. Our data highlight how the aberrant expression of miR-433 can adversely affect intracellular signaling to mediate chemoresistance in OC cells by driving cellular senescence.