Predicting Cognitive Functioning for Patients with a High-Grade Glioma: Evaluating Different Representations of Tumor Location in a Common Space.

Cognitive functioning is increasingly considered when making treatment decisions for patients with a brain tumor in view of a personalized onco-functional balance. Ideally, one can predict cognitive functioning of individual patients to make treatment decisions considering this balance. To make accurate predictions, an informative representation of tumor location is pivotal, yet comparisons of representations are lacking. Therefore, this study compares brain atlases and principal component analysis (PCA) to represent voxel-wise tumor location. Pre-operative cognitive functioning was predicted for 246 patients with a high-grade glioma across eight cognitive tests while using different representations of voxel-wise tumor location as predictors. Voxel-wise tumor location was represented using 13 different frequently-used population average atlases, 13 randomly generated atlases, and 13 representations based on PCA. ElasticNet predictions were compared between representations and against a model solely using tumor volume. Preoperative cognitive functioning could only partly be predicted from tumor location. Performances of different representations were largely similar. Population average atlases did not result in better predictions compared to random atlases. PCA-based representation did not clearly outperform other representations, although summary metrics indicated that PCA-based representations performed somewhat better in our sample. Representations with more regions or components resulted in less accurate predictions. Population average atlases possibly cannot distinguish between functionally distinct areas when applied to patients with a glioma. This stresses the need to develop and validate methods for individual parcellations in the presence of lesions. Future studies may test if the observed small advantage of PCA-based representations generalizes to other data.

A prospective study of incidence and outcome of acute kidney injury among hospitalised patients in Malaysia (My-AKI).

INTRODUCTION: The incidence of acute kidney injury (AKI) among hospitalised patients has not been well studied in Malaysia. MATERIALS AND METHODS: We conducted a prospective, multicentre study in seven hospitals in West Malaysia. All the adults admitted in March 2017 fulfilling Kidney Disease Improving Global Outcomes (KDIGO) criteria for AKI were included. RESULTS: Of the 34,204 patients screened, 2,457 developed AKI (7.18%), 13.1% of which occurred in intensive care unit (ICU). There were 60.2% males with a mean age of 57.8 (±17.5) years. The most common comorbidities were hypertension (55.0%), diabetes (46.6%), ischaemic heart disease (15.1%) and chronic kidney disease (12.0%). The commonest causes of AKI were sepsis (41.7%), pre-renal (24.2%) and cardiorenal syndrome (10.8%). Nephrotoxin exposure was reported in 31%. At diagnosis, the proportion of AKI stages 1, 2 and 3 were 79.1%, 9.7%, 11.2%, respectively. Referral to nephrologists was reported in 16.5%. Dialysis was required in 176 (7.2%) patients and 55.6% were performed in the ICU. Acidosis (46.2%), uraemia (31.6%) and electrolyte disturbance (11.1%) were the commonest indications. Continuous renal replacement therapy (CRRT) was required in 14%. The average length of hospital stay was 9.5 days. In-hospital mortality was 16.4%. Among survivors, full and partial renal recovery was seen in 74.7% and 16.4% respectively while 8.9% failed to recover. After a mean follow-up of 13.7 months, 593 (30.2%) of survivors died and 38 (1.9%) initiated chronic dialysis. Mortality was highest among those with malignancies (Hazard Ratio, HR 2.14), chronic liver disease (HR 2.13), neurological disease (HR 1.56) and cardiovascular disease (HR 1.17). CONCLUSION: AKI is common in hospitalised patients and is with associated high mortality during and after hospitalisation.

Evaluation of learning and exposure in the undergraduate interventional radiology curriculum (ELIXIR).

AIM: To gauge current final year medical students' exposure to interventional radiology (IR)and assess their perceptions of IR as a prospective career option. MATERIALS AND METHODS: An online questionnaire comprising of questions that gauge final-year medical students' understanding of and exposure to IR based on the recommendations set out by the British Society of Interventional Radiology (BSIR), was sent out to final-year students across 34 UK medical schools. RESULTS: Five hundred and ten responses were collected from 33 out of 34 eligible medical schools. Sixty-four per cent of respondents rated their own IR knowledge as inadequate. On average, only 50% of all subtopics proposed in the BSIR undergraduate curriculum was covered during medical school and 32.7% of respondents were not exposed to any fundamental IR principles and techniques recommended by the BSIR during medical school. Regarding careers, 2.7% of respondents reported a definite interest in pursuing a career in IR. Most respondents (89.8%) felt that there was insufficient undergraduate teaching on IR and that they lacked information to consider pursuing a career in IR (87.5%). CONCLUSION: Insufficient exposure and teaching on IR throughout medical schools have led to a lack of awareness and consideration of IR as a future career choice amongst UK medical students. The re-evaluation of IR teaching in the medical school curricula is needed. In the long-term, such recommendations could provide the much-needed solution to the workforce shortages seen in IR.

Predicting vasovagal reactions to needles with anticipatory facial temperature profiles.

Around one-third of adults are scared of needles, which can result in adverse emotional and physical responses such as dizziness and fainting (e.g. vasovagal reactions; VVR) and consequently, avoidance of healthcare, treatments, and immunizations. Unfortunately, most people are not aware of vasovagal reactions until they escalate, at which time it is too late to intervene. This study aims to investigate whether facial temperature profiles measured in the waiting room, prior to a blood donation, can be used to classify who will and will not experience VVR during the donation. Average temperature profiles from six facial regions were extracted from pre-donation recordings of 193 blood donors, and machine learning was used to classify whether a donor would experience low or high levels of VVR during the donation. An XGBoost classifier was able to classify vasovagal groups from an adverse reaction during a blood donation based on this early facial temperature data, with a sensitivity of 0.87, specificity of 0.84, F1 score of 0.86, and PR-AUC of 0.93. Temperature fluctuations in the area under the nose, chin and forehead have the highest predictive value. This study is the first to demonstrate that it is possible to classify vasovagal responses during a blood donation using temperature profiles.

Changes in blood pressure after Messenger RNA COVID-19 vaccination.

The SARS-Cov-2 (COVID-19) vaccination began in Malaysia in March 2021 among frontliners and healthcare workers. Everyone at our hospital received the tozinameran (BNT162b2) Messenger RNA COVID-19 vaccine. Although hypertension has not been mentioned explicitly as an adverse event, concerns were raised after some healthcare staff observed an increase in their blood pressures. In response to that, the hospital began collecting vital signs during second-dose appointments. Vital signs were measured before, immediately after and 15-30 minutes postvaccination. We report our findings from the institution-wide effort to monitor changes in blood pressure among its staff and respond to any possible unwanted events.

A Cost-Effective Alternative for Lateral Femoral Wall Perforation in Anterior Cruciate Ligament (ACL) Reconstruction: A Case Report.

Lateral femoral wall perforation is a rare intra-operative complication in anterior cruciate ligament (ACL) reconstruction surgery. However, it can be challenging to manage if it occurs. We share our experience on lateral femoral wall perforation managed by a large fragment washer. A 25-year-old man with right ACL injury presented with knee instability despite physiotherapy. Anterior drawer test (ADT) and Lachman test were grade 3, glide on pivot shift was positive. During ACL reconstruction, the lateral femoral wall was perforated. Due to unavailability of the rescue endobutton and budget constraint, we passed the endobutton through a washer and allowed it to sit on the washer over the lateral femoral wall. ADT and Lachman test on post-operative 6, 12 and 24 weeks were grade 1, with a negative pivot shift test. Lysholm knee score improved from 69 pre-operatively to 98 post-operatively. Conventionally, lateral femoral wall perforation can be managed by rescue endobutton, or screw and washer post technique. As this complication is rare, the rescue endobutton may not be available at all times, and the cost of the implant is also another important factor to consider. A washer can be used as an alternative technique to manage lateral femoral wall perforation in ACL reconstruction as it is not only cost-effective but also provides stable fixation with good functional outcome.

Triage of urology referrals and outpatient service during COVID-19 pandemic: experience from a single centre in Malaysia.

In Malaysia, COVID-19 pandemic recorded considerable number of cases. Many hospitals have been converted into COVID-19 centres to manage these cases. The Penang General Hospital was designated as a hybrid hospital to manage both COVID-19 and non-COVID-19 cases. Consequently, services across specialties, including urology have been affected. Triage of referrals was necessary to ensure optimum patient care, thus we designed a triage system to address this situation. A record screening system of patients was also implemented to limit outpatient appointments. We share this early experience in managing urology patients during this pandemic.

Microstructural abnormalities found in uncinate fasciculus and superior cerebellar tracts in children with global developmental delay: a feasibility study.

AIM: To evaluate the microstructural abnormalities of the white matter tracts (WMT) using diffusion tensor imaging (DTI) in children with global developmental delay (GDD). MATERIALS AND METHODS: Sixteen children with GDD underwent magnetic resonance imaging (MRI) and cross-sectional DTI. Formal developmental assessment of all GDD patients was performed using the Mullen Scales of Early Learning. An automated processing pipeline for the WMT assessment was implemented. The DTI-derived metrics of the children with GDD were compared to healthy children with normal development (ND). RESULTS: Only two out of the 17 WMT demonstrated significant differences (p<0.05) in DTI parameters between the GDD and ND group. In the uncinate fasciculus (UF), the GDD group had lower mean values for fractional anisotropy (FA; 0.40 versus 0.44), higher values for mean diffusivity (0.96 versus 0.91×10-3 mm2/s) and radial diffusivity (0.75 versus 0.68×10-3 mm2/s) compared to the ND group. In the superior cerebellar peduncle (SCP), mean FA values were lower for the GDD group (0.38 versus 0.40). Normal myelination pattern of DTI parameters was deviated against age for GDD group for UF and SCP. CONCLUSION: The UF and SCP WMT showed microstructural changes suggestive of compromised white matter maturation in children with GDD. The DTI metrics have potential as imaging markers for inadequate white matter maturation in GDD children.

A High-Throughput BRET Cellular Target Engagement Assay Links Biochemical to Cellular Activity for Bruton's Tyrosine Kinase.

Protein kinases are intensely studied mediators of cellular signaling. While traditional biochemical screens are capable of identifying compounds that modulate kinase activity, these assays are limited in their capability of predicting compound behavior in a cellular environment. Here, we aim to bridge target engagement and compound-cellular phenotypic behavior by utilizing a bioluminescence resonance energy transfer (BRET) assay to characterize target occupancy within living cells for Bruton's tyrosine kinase (BTK). Using a diverse chemical set of BTK inhibitors, we determine intracellular engagement affinity profiles and successfully correlate these measurements with BTK cellular functional readouts. In addition, we leveraged the kinetic capability of this technology to gain insight into in-cell target residence time and the duration of target engagement, and to explore a structural hypothesis.

The impact of music guided deep breathing exercise on blood pressure control - A participant blinded randomised controlled study.

INTRODUCTION: As pharmacological treatment of hypertension has become a burden worldwide, the study looked into nonpharmacological ways of reducing blood pressure. The objective was to determine if music guided, slow and deep breathing will reduce the blood pressure among patients with hypertension in eight weeks. METHODS: A participant blinded, multi-centre, randomised controlled trial was conducted in which the participants in the intervention group (IG) practiced deep breathing exercise guided by sound cues and those in the control group (CG) listened to the music. The primary end point was reduction in blood pressure at eight weeks. RESULTS: 87 patients, 46 males and 41 females with mean age of 61.1 years were recruited and 93.1% of them successfully completed the study. There was significant reduction in systolic and diastolic Blood Pressure from baseline by 8 weeks in both groups. The reduction in Mean systolic blood pressure (SBP) in the control arm was 10.5mmHg compared to 8.3mmHg (p<0.001) in intervention group. Diastolic blood pressure (DBP) reduction in control and intervention groups were 5.2 mmHg (p<0.001) and 5.6 mmHg (p<0.001) respectively. The absolute difference in SBP reduction from baseline in IG & CG was -2.2 (95%CI: -7.8 to 3.5) and DBP was -0.4 (95%CI: -2.9 to 3.6). However, blood pressure reduction between the two groups was not significant. CONCLUSIONS: Both listening to music and deep breathing exercise were associated with a clinically significant reduction in SBP and DBP. However, deep breathing exercise did not augment the benefit of music in reducing BP.

A fluorescence in situ staining method for investigating spores and vegetative cells of Clostridia by confocal laser scanning microscopy and structured illuminated microscopy.

Non-pathogenic spore-forming Clostridia are of increasing interest due to their application in biogas production and their capability to spoil different food products. The life cycle for Clostridium includes a spore stage that can assist in survival under environmentally stressful conditions, such as extremes of temperature or pH. Due to their size, spores can be investigated by a range of microscopic techniques, many of which involve sample pre-treatment. We have developed a quick, simple and non-destructive fluorescent staining procedure that allows a clear differentiation between spores and vegetative cells and effectively stains spores, allowing recovery and tracking in subsequent experiments. Hoechst 34580, Propidium iodide and wheat germ agglutinin WGA 488 were used in combination to stain four strains of Clostridia at different life cycle stages. Staining was conducted without drying the sample, preventing changes induced by dehydration and cells observed by confocal laser scanner microscopy or using a super-resolution microscope equipped with a 3D-structured illumination module. Dual staining with Hoechst/Propidium iodide differentiated spores from vegetative cells, provided information on the viability of cells and was successfully applied to follow spore production induced by heating. Super-resolution microscopy of spores probed by Hoechst 34580 also allowed chromatin to be visualised. Direct staining of a cheese specimen using Nile Red and Fast Green allowed in situ observation of spores within the cheese and their position within the cheese matrix. The proposed staining method has broad applicability and can potentially be applied to follow Clostridium spore behaviour in a range of different environments.

Eleven quick tips for running an interdisciplinary short course for new graduate students.

Quantitative reasoning and techniques are increasingly ubiquitous across the life sciences. However, new graduate researchers with a biology background are often not equipped with the skills that are required to utilize such techniques correctly and efficiently. In parallel, there are increasing numbers of engineers, mathematicians, and physical scientists interested in studying problems in biology with only basic knowledge of this field. Students from such varied backgrounds can struggle to engage proactively together to tackle problems in biology. There is therefore a need to establish bridges between those disciplines. It is our proposal that the beginning of graduate school is the appropriate time to initiate those bridges through an interdisciplinary short course. We have instigated an intensive 10-day course that brought together new graduate students in the life sciences from across departments within the National University of Singapore. The course aimed at introducing biological problems as well as some of the quantitative approaches commonly used when tackling those problems. We have run the course for three years with over 100 students attending. Building on this experience, we share 11 quick tips on how to run such an effective, interdisciplinary short course for new graduate students in the biosciences.

Effect of temperature on the microstructure of fat globules and the immunoglobulin-mediated interactions between fat and bacteria in natural raw milk creaming.

Natural creaming of raw milk is the first step in production of Grana Padano and Parmigiano Reggiano Protected Denomination of Origin cheeses. This process decreases the fat content and plays an important role in the removal of clostridia species that may cause late-blowing defects in ripened cheeses. Partial coalescence of fat globules-that may influence fat behavior in cheese making and affect the microstructure of fat in the final cheese product-was observed at creaming temperatures higher than 22°C by confocal laser scanning microscopy. The widespread practice of heating of milk at 37°C before creaming at 8°C resulted in important changes in the size distribution of fat globules in raw milk, potentially altering the ability of fat to entrap clostridia spores. We investigated the role of immunoglobulin classes in both the clustering of fat globules and the agglutination of Clostridium tyrobutyricum to fat globules during creaming. Immunogold labeling and transmission electron microscopy showed that IgA and IgM but not IgG were involved in both clustering and agglutination. Both vegetative cells and spores were clearly shown to agglutinate to fat droplets, a process that was suppressed by thermal denaturation of the immunoglobulins. The debacterization of raw milk through natural creaming was improved by the addition of purified immunoglobulins. Overall, these findings provide not only a better understanding of the phenomena occurring during the natural creaming but also practical insights into how the process of creaming may be optimized in cheese production plants.

Does initial routine use of a compression garment reduce the risk of lower limb lymphedema after gynecological cancer treatment? A randomized pilot study in an Asian institution and review of the literature.

This is a randomized pilot study evaluating the effectiveness of customized compression garments (CG) in reducing the risk of lower limb lymphedema (LLL) in gynecological cancer patients. Patients who completed pelvic node dissection or radiation were routinely educated on reducing the risk of LLL by good skin care and manual lymphatic massage. After baseline lower limb volume perometry and clinical assessment, they were randomized to customized compression garment (CG) for 6 weeks (26 patients) or observation (30 patients). Both groups were followed up for 2 years and the primary outcome was the development of LLL. LLL incidence in the control group was 13.3% (4 of 30 patients) compared to 7.7% (2 of 26 patients) in the CG group. However the difference was not statistically significant (P=0.496). In the control group, 10.7% (3/28) who underwent node dissection developed LLL vs 7.7% (2/26) in the CG group. Among patients with node dissection plus radiation, LLL incidence was 14.3% (1/7) in the control group vs 12.5% (1/8) in the CG group. The mean onset of LLL was 12 months; compliance to CG wearing was high and QOL scores were similar in both groups. Customized low-compression CG worn for 6 weeks may have a possible benefit in reducing the risk of LLL when added to patient education on risk reduction although statistic significance was not achieved in this small pilot study. A larger multi-center study would be justified to expand these findings.

The impact of epilepsy on academic achievement in children with normal intelligence and without major comorbidities: A systematic review.

PURPOSE: To systematically examine published literature which assessed the prevalence of academic difficulties in children with epilepsy (CWE) of normal intelligence, and its associating factors. METHODS: A search was conducted on five databases for articles published in English from 1980 till March 2015. Included were studies who recruited children (aged 5-18 years), with a diagnosis or newly/recurrent epilepsy, an intelligent quotient (IQ) of ≥70 or attending regular school, with or without a control group, which measured academic achievement using a standardised objective measure, and published in English. Excluded were children with learning difficulties, intellectual disabilities (IQ<70) and other comorbidities such as attention deficits hyperactive disorder or autism. Two pairs of reviewers extracted the data, and met to resolve any differences from the data extraction process. RESULTS: Twenty studies were included. The majority of the studies assessed "low achievement" whist only two studies used the IQ-achievement discrepancy definition of "underachievement". Fourteen studies (70%) reported that CWE had significantly lower academic achievement scores compared to healthy controls, children with asthma or reported norms. The remaining six studies (30%) did not report any differences. CWE had stable academic achievement scores over time (2-4 years), even among those whose seizure frequency improved. Higher parental education and children with higher IQ, and had better attention or had a positive attitude towards epilepsy, were associated with higher academic achievement score. Older children were found to have lower academic achievement score. CONCLUSIONS: In CWE of normal intelligence, the majority of published literature found that academic achievement was lower than controls or reported norms. The high percentages of low achievement in CWE, especially in the older age group, and the stability of scores even as seizure frequency improved, highlights the need for early screening of learning problems, and continued surveillance.

Challenges faced by older nurses in Singapore: a mixed methods study.

BACKGROUND: In Singapore, employees aged 62-65 can continue to be employed if they meet the re-employment eligibility criteria. This policy, coupled with an ageing workforce, calls for age-friendly initiatives, specific to work-related challenges faced by older nurses. AIM: To determine work-related challenges faced by older nurses. METHODS: A mixed method sequential explanatory study was conducted with nurses, aged 50 and above, working in a healthcare cluster in Singapore. In the quantitative phase, a questionnaire was administered to 534 nurses to elicit work-related challenges, then in-depth interviews with 30 nurses were carried out to help explain why certain tasks and work circumstances became harder. RESULTS: Results of the survey indicated that the top three challenges were coping with changes, working with computers and reading labels. Place of work, salary range, gender and race were significantly associated with different work-related challenges. Five themes emerged from the qualitative data: physical demands of work and workload, new technology, need for further education, working with younger nurses and in intercultural teams, and changing public expectations and professional image. DISCUSSION AND CONCLUSION: The study supports the current literature on the challenges older nurses face with technological advancement. However, older nurses in our study reported less aches and pain as compared to that reported elsewhere. There is a need for specific strategies that will address changes in work processes and environment in order to retain older nurses. IMPLICATIONS FOR NURSING AND NURSING POLICY: When devising age-friendly work improvement initiatives, it is important for nurse leaders to factor in the needs of nurses working in different care environments, who are of different ranks, or are from different ethnic backgrounds.

An enzyme-responsive controlled release system based on a dual-functional peptide.

A new controlled release system was developed by loading a dual-functional peptide (DFP) on a mesoporous silica material. One-pot synthesis produced a DFP that was stimuli responsive, releasing a therapeutic peptide by protease cleavage. The design provides new steps towards smart biomaterials.

Image classification of unlabeled malaria parasites in red blood cells.

This paper presents a method to detect unlabeled malaria parasites in red blood cells. The current "gold standard" for malaria diagnosis is microscopic examination of thick blood smear, a time consuming process requiring extensive training. Our goal is to develop an automate process to identify malaria infected red blood cells. Major issues in automated analysis of microscopy images of unstained blood smears include overlapping cells and oddly shaped cells. Our approach creates robust templates to detect infected and uninfected red cells. Histogram of Oriented Gradients (HOGs) features are extracted from templates and used to train a classifier offline. Next, the ViolaJones object detection framework is applied to detect infected and uninfected red cells and the image background. Results show our approach out-performs classification approaches with PCA features by 50% and cell detection algorithms applying Hough transforms by 24%. Majority of related work are designed to automatically detect stained parasites in blood smears where the cells are fixed. Although it is more challenging to design algorithms for unstained parasites, our methods will allow analysis of parasite progression in live cells under different drug treatments.

Protease-activated receptor 1 suppresses Helicobacter pylori gastritis via the inhibition of macrophage cytokine secretion and interferon regulatory factor 5.

Chronic gastritis from Helicobacter pylori infection is a major factor in the development of gastric adenocarcinoma. Factors that regulate gastritis severity are important in determining which individuals are susceptible to H. pylori-associated disease. Although protease-activated receptor 1 (PAR1) has been identified as one such host factor, its mechanism of action is unknown. Using chimeric mice, we demonstrated that PAR1-mediated protection against H. pylori gastritis requires bone marrow-derived cells. Analyses of the gastric mucosa revealed that PAR1 suppresses cellular infiltration and both T helper type 1 (Th1) and T helper type 17 (Th17) responses to infection. Moreover, PAR1 expression was associated with reduced vaccine-mediated protection against H. pylori. Analyses of H. pylori-stimulated macrophages revealed that PAR1 activation suppressed secretion of interleukin (IL)-12 and IL-23, key drivers of Th1 and Th17 immunity, respectively. Furthermore, PAR1 suppressed interferon regulatory factor 5 (IRF5), an important transcription factor for IL-12 and IL-23, both in the infected mucosa and following bacterial stimulation. PAR1 suppression of IRF5 and IL-12/23 secretion by macrophages provides a novel mechanism by which the host suppresses the mucosal Th1 and Th17 response to H. pylori infection. Dysregulation of this process is likely an important factor in the susceptibility of some individuals to H. pylori-associated disease.