Dengue virus infection and neurological manifestations: an update.

Dengue virus is a flavivirus transmitted by the mosquitoes, Aedes aegypti and Aedes albopictus. Dengue infection by all four serotypes (DEN 1 to 4) is endemic globally in regions with tropical and subtropical climates, with an estimated 100-400 million infections annually. Among those hospitalized, the mortality is about 1%. Neurological involvement has been reported to be about 5%. The spectrum of neurological manifestations spans both the peripheral and central nervous systems. These manifestations could possibly be categorized into those directly related to dengue infection, i.e. acute and chronic encephalitis, indirect complications leading to dengue encephalopathy, and post-infectious syndrome due to immune-mediated reactions, and manifestations with uncertain mechanisms, such as acute transverse myelitis, acute cerebellitis and myositis. The rising trend in global dengue incidence calls for attention to a more explicit definition of each neurological manifestation for more accurate epidemiological data. The actual global burden of dengue infection with neurological manifestation is essential for future planning and execution of strategies, especially in the development of effective antivirals and vaccines against the dengue virus. In this article, we discuss the recent findings of different spectrums of neurological manifestations in dengue infection and provide an update on antiviral and vaccine development and their challenges.

The effect of 20-minute mindful breathing exercise on psychological well-being in epilepsy: A pilot randomized controlled trial.

INTRODUCTION: Depression and anxiety are prevalent in epilepsy patients, but psychiatric or psychological services may not be accessible to all patients. This study aimed to determine the effectiveness of the 20-minute mindful breathing on the psychological well-being of PWE using an instructional video. METHOD: This was a pilot, assessor-blinded, randomized controlled trial. The intervention group received a guided video and was briefed to perform the exercise twice a week for two weeks while the waitlist control group only received the video upon completion of the study. The subjects were assessed at three-time points (T0: Baseline, T1: 2 weeks after the intervention, T2: 4 weeks after intervention), using the Neurological Disorders Depression Index (NDDI-E), General Anxiety Disorder (GAD-7), Quality of Life in Epilepsy Inventory (QOLIE-31) and Mindfulness Attention Awareness Scale (MAAS). RESULTS: Twenty patients were recruited, with 10 in the intervention and waitlist-control groups. Compared with the waitlist-control group, participants in the intervention group showed significant improvement in NDDI-E at T1 (p = 0.022) but not at T2 (p = 0.056) and greater improvement in GAD-7 at T1 and T2 but not statistically significant. The QOLIE-31 overall score in the intervention group has significantly improved at T1 (p = 0.036) and T2 (p = 0.031) compared to the waitlist-control group. For MAAS, the intervention group also had an increased score at T2 (p = 0.025). CONCLUSION: The 20-minute mindfulness breathing exercise has an immediate effect in improving depression and quality of life among people with epilepsy.

Whole transcriptome analysis and construction of a ceRNA regulatory network related to leaf and petiole development in Chinese cabbage (Brassica campestris L. ssp. pekinensis).

BACKGROUND: The growth and development of leaves and petioles have a significant effect on photosynthesis. Understanding the molecular mechanisms underlying leaf and petiole development is necessary for improving photosynthetic efficiency, cultivating varieties with high photosynthetic efficiency, and improving the yield of crops of which the leaves are foodstuffs. This study aimed to identify the mRNAs, long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs) related to leaf and petiole development in Chinese cabbage (Brassica campestris L. ssp. pekinensis). The data were used to construct a competitive endogenous RNA (ceRNA) network to obtain insights into the mechanisms underlying leaf and petiole development. RESULTS: The leaves and petioles of the 'PHL' inbred line of Chinese cabbage were used as research materials for whole transcriptome sequencing. A total of 10,646 differentially expressed (DE) mRNAs, 303 DElncRNAs, 7 DEcircRNAs, and 195 DEmiRNAs were identified between leaves and petioles. Transcription factors and proteins that play important roles in leaf and petiole development were identified, including xyloglucan endotransglucosylase/hydrolase, expansion proteins and their precursors, transcription factors TCP15 and bHLH, lateral organ boundary domain protein, cellulose synthase, MOR1-like protein, and proteins related to plant hormone biosynthesis. A ceRNA regulatory network related to leaf and petiole development was constructed, and 85 pairs of ceRNA relationships were identified, including 71 DEmiRNA-DEmRNA, 12 DEmiRNA-DElncRNA, and 2 DEmiRNA-DEcircRNA pairs. Three LSH genes (BrLSH1, BrLSH2 and BrLSH3) with significant differential expression between leaves and petioles were screened from transcriptome data, and their functions were explored through subcellular localization analysis and transgenic overexpression verification. BrLSH1, BrLSH2 and BrLSH3 were nuclear proteins, and BrLSH2 inhibited the growth and development of Arabidopsis thaliana. CONCLUSIONS: This study identifies mRNAs and non-coding RNAs that may be involved in the development of leaves and petioles in Chinese cabbage, and establishes a ceRNA regulatory network related to development of the leaves and petioles, providing valuable genomic resources for further research on the molecular mechanisms underlying leaf and petiole development in this crop species.

Genome-wide identification and expression analysis of the GASA gene family in Chinese cabbage (Brassica rapa L. ssp. pekinensis).

BACKGROUND: The Gibberellic Acid-Stimulated Arabidopsis (GASA) gene family is widely involved in the regulation of plant growth, development, and stress response. However, information on the GASA gene family has not been reported in Chinese cabbage (Brassica rapa L. ssp. pekinensis). RESULTS: Here, we conducted genome-wide identification and analysis of the GASA genes in Chinese cabbage. In total, 15 GASA genes were identified in the Chinese cabbage genome, and the physicochemical property, subcellular location, and tertiary structure of the corresponding GASA proteins were elucidated. Phylogenetic analysis, conserved motif, and gene structure showed that the GASA proteins were divided into three well-conserved subfamilies. Synteny analysis proposed that the expansion of the GASA genes was influenced mainly by whole-genome duplication (WGD) and transposed duplication (TRD) and that duplication gene pairs were under negative selection. Cis-acting elements of the GASA promoters were involved in plant development, hormonal and stress responses. Expression profile analysis showed that the GASA genes were widely expressed in different tissues of Chinese cabbage, but their expression patterns appeared to diverse. The qRT-PCR analysis of nine GASA genes confirmed that they responded to salt stress, heat stress, and hormonal triggers. CONCLUSIONS: Overall, this study provides a theoretical basis for further exploring the important role of the GASA gene family in the functional genome of Chinese cabbage.

Identification of a new allele of BraA09g066480.3C controlling the wax-less phenotype of Chinese cabbage.

BACKGROUND: Epidermal wax covers the surfaces of terrestrial plants to resist biotic and abiotic stresses. Wax-less flowering Chinese cabbage (Brassica campestris L. ssp. chinesis var. utilis tsen et lee) has the charateristics of lustrous green leaves and flower stalks, which are of high commercial value. RESULTS: To clarify the mechanism of the wax deficiency, the wax-less flowering Chinese cabbage doubled-haploid (DH) line 'CX001' and Chinese cabbage DH line 'FT', obtained from isolated microspore culture, were used in the experiments. Genetic analysis showed that the wax-less phenotype of 'CX001' was controlled by a recessive nuclear gene, named wlm1 (wax-less mutation 1), which was fine-mapped on chromosome A09 by bulked segregant analysis sequencing (BSA-seq) of B.rapa genome V3.0. There was only one gene (BraA09g066480.3C) present in the mapping region. The homologous gene in Arabidopsis thaliana is AT1G02205 (CER1) that encodes an aldehyde decarboxylase in the epidermal wax metabolism pathway. Semi-quantitative reverse transcription PCR and transcriptome analysis indicated that BraA09g066480.3C was expressed in 'FT' but not in 'CX001'. BraA09g066480.3C was lost in the CXA genome to which 'CX001' belonged. CONCLUSION: The work presented herein demonstrated that BraA09g066480.3C was the causal gene for wax-less flowering Chinese cabbage 'CX001'. This study will lay a foundation for further research on the molecular mechanism of epidermal wax synthesis in flowering Chinese cabbage.

High-performance narrowband thermal emitter based on aperiodic Tamm plasmon structures assisted by inverse design.

Controlling the bandwidth and directionality of thermal emission is important for a broad range of applications, from imaging and sensing to energy harvesting. Here, we propose a new, to the best of our knowledge, type of long-wavelength infrared narrowband thermal emitter that is basically composed of aperiodic Tamm plasmon polariton structures. Compared to the thermal emitter based on periodic structures, more parameters need to be considered. An inverse design algorithm instead of traditional forward methodologies is employed to do the geometric parameter optimization. Both theoretical and experimental results show that the thermal emitter exhibits a narrowband thermal emission peak at the wavelength of 8.6 µm in the normal direction. The angular response of emission properties of the thermal emitter is dependent on the emission angle. We believe that our proposed thermal emitter provides an alternative for low-cost, high-effective narrowband mid-infrared light sources and would have a great potential in many applications.

Narrowband HgCdTe infrared photodetector with integrated plasmonic structure.

The application of plasmonic structure has been demonstrated to improve the performance of infrared photodetectors. However, the successful experimental realization of the incorporation of such optical engineering structure into HgCdTe-based photodetectors has rarely been reported. In this paper, we present a HgCdTe infrared photodetector with integrated plasmonic structure. The experimental results show that the device with plasmonic structure has a distinct narrowband effect with a peak response rate close to 2 A/W, which is nearly 34% higher compared with the reference device. The simulation results are in good agreement with the experiment, and an analysis of the effect of the plasmonic structure is given, demonstrating the crucial role of the plasmonic structure in the enhancement of the device performance.

Role of Brassica orphan gene BrLFM on leafy head formation in Chinese cabbage (Brassica rapa).

KEY MESSAGE: Brassica orphan gene BrFLM, identified by two allelic mutants, was involved in leafy head formation in Chinese cabbage. Leafy head formation is a unique agronomic trait of Chinese cabbage that determines its yield and quality. In our previous study, an EMS mutagenesis Chinese cabbage mutant library was constructed using the heading Chinese cabbage double haploid (DH) line FT as the wild-type. Here, we screened two extremely similar leafy head deficiency mutants lfm-1 and lfm-2 with geotropic growth leaves from the library to investigate the gene(s) related to leafy head formation. Reciprocal crossing results showed that these two mutants were allelic. We utilized lfm-1 to identify the mutant gene(s). Genetic analysis showed that the mutated trait was controlled by a single nuclear gene Brlfm. Mutmap analysis showed that Brlfm was located on chromosome A05, and BraA05g012440.3C or BraA05g021450.3C were the candidate gene. Kompetitive allele-specific PCR analysis eliminated BraA05g012440.3C from the candidates. Sanger sequencing identified an SNP from G to A at the 271st nucleotide on BraA05g021450.3C. The sequencing of lfm-2 detected another non-synonymous SNP (G to A) located at the 266st nucleotide on BraA05g021450.3C, which verified its function on leafy head formation. We blasted BraA05g021450.3C on database and found that it belongs to a Brassica orphan gene encoding an unknown 13.74 kDa protein, named BrLFM. Subcellular localization showed that BrLFM was located in the nucleus. These findings reveal that BrLFM is involved in leafy head formation in Chinese cabbage.

Affordability of newer antiseizure medications in Asian resource-limited countries.

OBJECTIVE: One of the objectives of the Intersectoral Global Action Plan on epilepsy and other neurological disorders for 2022 to 2031 is to ensure at least 80% of people with epilepsy (PWE) will have access to appropriate, affordable, and safe antiseizure medications (ASMs) by 2031. However, ASM affordability is a significant issue in low- and middle-income countries, preventing PWE from accessing optimal treatment. This study aimed to determine the affordability of the newer (second and third generation) ASMs in resource-limited countries in Asia. METHODS: We conducted a cross-sectional survey by contacting country representatives in lower-middle-income countries (LMICs) in Asia, including Indonesia, Lao People's Democratic Republic (PDR), Myanmar, Philippines, Vietnam, India, Bangladesh, and Pakistan, and the upper-middle-income country Malaysia, from March 2022 to April 2022. The affordability of each ASM was calculated by dividing the 30-day ASM cost by the daily wage of the lowest paid unskilled laborers. Treatment costing 1 day's wage or less for a 30-day supply of chronic disease is considered affordable. RESULTS: Eight LMICs and one upper-middle-income country were included in this study. Lao PDR had no newer ASM, and Vietnam had only three newer ASMs. The most frequently available ASMs were levetiracetam, topiramate, and lamotrigine, and the least frequently available was lacosamide. The majority of the newer ASMs were unaffordable, with the median number of days' wages for a 30-day supply ranging from 5.6 to 14.8 days. SIGNIFICANCE: All new generation ASMs, whether original or generic brands, were unaffordable in most Asian LMICs.

MOAP-1-mediated dissociation of p62/SQSTM1 bodies releases Keap1 and suppresses Nrf2 signaling.

Nrf2 signaling is vital for protecting cells against oxidative stress. However, its hyperactivation is frequently found in liver cancer through excessive build-up of p62/SQSTM1 bodies that sequester Keap1, an adaptor of the E3-ubiquitin ligase complex for Nrf2. Here, we report that the Bax-binding protein MOAP-1 regulates p62-Keap1-Nrf2 signaling through disruption of p62 bodies. Upon induction of cellular stresses that stimulate formation of p62 bodies, MOAP-1 is recruited to p62 bodies and reduces their levels independent of the autophagy pathway. MOAP-1 interacts with the PB1-ZZ domains of p62 and interferes with its self-oligomerization and liquid-liquid phase separation, thereby disassembling the p62 bodies. Loss of MOAP-1 can lead to marked upregulation of p62 bodies, enhanced sequestration of Keap1 by p62 and hyperactivation of Nrf2 antioxidant target genes. MOAP-1-deficient mice exhibit an elevated tumor burden with excessive levels of p62 bodies and Nrf2 signaling in a diethylnitrosamine (DEN)-induced hepatocarcinogenesis model. Together, our data define MOAP-1 as a negative regulator of Nrf2 signaling via dissociation of p62 bodies.

The management and clinical outcomes of pregnancies in women with urea cycle disorders: A review of the literature and results of an international survey.

An increasing number of women with urea cycle disorders (UCDs) are reaching child-bearing age and becoming pregnant. Improved diagnostics and increased awareness of inherited metabolic diseases has also led to more previously undetected women being diagnosed with a UCD during or shortly after pregnancy. Pregnancy increases the risk of acute metabolic decompensation with hyperammonemia-which can occur in any trimester, and/or the postpartum period, and may lead to encephalopathy, psychosis, coma, and even death, if not diagnosed promptly and treated appropriately. There are also (theoretical) concerns that a maternal UCD, or its treatment, may cause potential risks for the unborn child. Currently evidence on management and outcome of pregnancies in UCDs is limited to case reports and there are no clear guidelines. In order to inform management and investigate outcomes of pregnancies in women with a UCD, we performed a retrospective review of published cases and analyzed data collected from an international online survey. We conclude that, although risk during the intra- and postpartum period exists, multidisciplinary management by an experienced team and a prospective plan usually result in successful pregnancy, labor, delivery, and postpartum period. No deaths were reported in mothers managed accordingly. With the exception of male neonates with Ornithine Transcarbamylase deficiency, the clinical outcome of children born to mothers with UCDs appears positive, although follow-up is limited. The outcome for women presenting with a first acute metabolic decompensation during pregnancy or postpartum is less favorable. Deaths were associated with diagnostic delay/late management of hyperammonemia in previously undiagnosed women.

Caregiver burden for adults with epilepsy in Malaysian families: A qualitative study.

BACKGROUND: Caregivers of adults with epilepsy (AWE) play an important role in the healthcare pathway of AWE and are described as the "co-client." Being caregivers can be stressful and the negative impacts might accumulate over time, affecting their quality of life and well-being. OBJECTIVES: This qualitative study aimed to explore the lived experience of caregivers of AWE in Malaysian families and understand their caregiving challenges. Individual semi-structured interviews were held with 12 primary caregivers of AWE. Interpretative Phenomenological Approach (IPA) was used. The interview transcripts were analyzed using NVivo12 software. RESULTS: Primary caregivers of AWE were parents or siblings, with ages ranging from 56 to 80 years old and years of caregiving from 24 to 40 years. Most AWE (58%) were intellectually disabled and fully dependent on ADL needs. Two categories of themes emerged, including four themes on caregiver burden, i.e., physical, emotional, and social burdens, and challenges in future planning of care, and two themes on coping strategies (problem- or emotional-focused). In future planning of care, most caregivers especially parents carried a burden of responsibility and were reluctant to depend on others or institutional services. CONCLUSION: The caregiving burden among caregivers for adult AWE was not confined to current burdens only but also challenges in future planning. A better understanding of the caregiving burden for AWE and coping strategies is needed to provide tailored psychoeducation or psychosocial intervention to support this population.

Feasibility of psychological screening in a tertiary epilepsy clinic.

OBJECTIVE: People with epilepsy (PWE) have a high prevalence of developing depression and anxiety. The objective is to determine the feasibility of brief screening tools to screen for depression and anxiety in epilepsy, and the predictive factors. METHOD: This is a cross-sectional study in the neurology clinic in a tertiary teaching hospital in Kuala Lumpur. The screening tools used were the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) and the General Anxiety Disorder Form (GAD-7). RESULTS: Five hundred and eighty-five patients were recruited in this study, and 50.8% of them were male, predominantly Chinese (46.7%), with a mean age of seizure onset of 21.8 ± 16.1 years. The majority had focal seizures (75.0%), and 41.9% had seizure remission. There were 15.5% who scored ≥15 in the NDDI-E, and 17.0% had moderate or severe anxiety (scored ≥10 in the GAD-7). In a regression model to predict the NDDI-E score, the age of seizure onset recorded a higher beta value (ß = -0.265, p =< 0.001), followed by the duration of epilepsy (ß = -0.213, p =< 0.001), use of levetiracetam (LEV) (ß = 0.147, p = 0.002), clonazepam (CLZ) (ß = 0.127, p = 0.011), and lamotrigine (LTG) (ß = 0.125, p = 0.011), number of current antiseizure medications (ß = -0.124, p = 0.049), seizure remission for ≥1 year (ß = -0.108, p = 0.011), and female (ß = 0.082, p = 0.049). For the GAD-7 score, the predictors included current age (ß = -0.152, p = 0.001), the use of LEV (ß = 0.122, p = 0.011), Indian ethnicity (ß = 0.114, p = 0.006), and the use of carbamazepine (ß = -0.090, p = 0.043). CONCLUSION: Implementation of simple psychological screening using self-administered questionnaires was feasible in a busy tertiary epilepsy clinic.

Low tidal volume ventilation for patients undergoing laparoscopic surgery: a secondary analysis of a randomised clinical trial.

BACKGROUND: We recently reported the results for a large randomized controlled trial of low tidal volume ventilation (LTVV) versus conventional tidal volume (CTVV) during major surgery when positive end expiratory pressure (PEEP) was equal between groups. We found no difference in postoperative pulmonary complications (PPCs) in patients who received LTVV. However, in the subgroup of patients undergoing laparoscopic surgery, LTVV was associated with a numerically lower rate of PPCs after surgery. We aimed to further assess the relationship between LTVV versus CTVV during laparoscopic surgery. METHODS: We conducted a post-hoc analysis of this pre-specified subgroup. All patients received volume-controlled ventilation with an applied PEEP of 5 cmH2O and either LTVV (6 mL/kg predicted body weight [PBW]) or CTVV (10 mL/kg PBW). The primary outcome was the incidence of a composite of PPCs within seven days. RESULTS: Three hundred twenty-eight patients (27.2%) underwent laparoscopic surgeries, with 158 (48.2%) randomised to LTVV. Fifty two of 157 patients (33.1%) assigned to LTVV and 72 of 169 (42.6%) assigned to conventional tidal volume developed PPCs within 7 days (unadjusted absolute difference, - 9.48 [95% CI, - 19.86 to 1.05]; p = 0.076). After adjusting for pre-specified confounders, the LTVV group had a lower incidence of the primary outcome than patients receiving CTVV (adjusted absolute difference, - 10.36 [95% CI, - 20.52 to - 0.20]; p = 0.046). CONCLUSION: In this post-hoc analysis of a large, randomised trial of LTVV we found that during laparoscopic surgeries, LTVV was associated with a significantly reduced PPCs compared to CTVV when PEEP was applied equally between both groups. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry no: 12614000790640.

Integrated Physiological and Transcriptomic Analyses Revealed Improved Cold Tolerance in Cucumber (Cucumis sativus L.) by Exogenous Chitosan Oligosaccharide.

Cucumber (Cucumis sativus L.), sensitive to cold stress, is one of the most economically important vegetables. Here, we systematically investigated the roles of exogenous glycine betaine, chitosan, and chitosan oligosaccharide in alleviating cold stress in cucumber seedlings. The results showed that 50 mg·L-1 chitosan oligosaccharide had the best activity. It effectively increases plant growth, chlorophyll content, photosynthetic capacity, osmotic regulatory substance content, and antioxidant enzyme activities while reducing relative electrical conductivity and malondialdehyde levels in cucumber seedlings under cold stress. To reveal the protective effects of chitosan oligosaccharide in cold stress, cucumber seedlings pretreated with 50 mg·L-1 chitosan oligosaccharide were sampled after 0, 3, 12, and 24 h of cold stress for transcriptome analysis, with distilled water as a control. The numbers of differentially expressed genes in the four comparison groups were 656, 1274, 1122, and 957, respectively. GO functional annotation suggested that these genes were mainly involved in "voltage-gated calcium channel activity", "carbohydrate metabolic process", "jasmonic acid biosynthetic", and "auxin response" biological processes. KEGG enrichment analysis indicated that these genes performed important functions in "phenylpropanoid biosynthesis", "MAPK signaling pathway-plant", "phenylalanine metabolism", and "plant hormone signal transduction." These findings provide a theoretical basis for the use of COS to alleviate the damage caused by cold stress in plant growth and development.

Use of a buprenorphine-based pain management protocol is associated with reduced opioid requirements and pain on swallowing in oral mucositis: a retrospective cohort study.

OBJECTIVE: The aim of this study is to ascertain the analgesic efficacy and total oral morphine equivalent daily dose (OMEDD) effect of a buprenorphine-based analgesic protocol in the treatment of severe Oral Mucositis (OM). DESIGN: This is a retrospective cohort study. SETTING: This study was done in a single Quaternary Referral Centre, Haematology Unit. SUBJECTS: Fifty-four stem cell transplant patients suffering at least grade 3 oral mucositis (OM), 24 prior to [Pr-I] and 30 subsequent to [Po-I] a buprenorphine-based OM analgesic protocol. METHODS: We analysed data from the above subjects with the primary outcome measure of difference in total OMEDDs from all opioid types and administration routes, and secondary outcome measures of area under the curve (AUC) of 11-point Numerical Rating Scale (NRS-11) pain assessments, sedation scores and respiratory rate. RESULTS: Post-protocol patients' total OMEDD requirements were significantly reduced [Pr-I: 1961 (1365)mg; Po-I: 928 (625)mg, p = 0.02], as were total NRS-11:hours AUC on swallowing [Pr-I: 54(24) score-hours; Po-I: 41(18) score-hours, p < 0.001]. There were no significant differences in objective measures of OM severity between groups (Number of Grade 3 or 4 OM severity assessments [mean (SD)] Pr-I: 5 (6.2); Po-I: 7 (5.1) or number of days Neutrophil count 0.0 or 0.1 × 109/L; Pr-I: 13 (5.4); Po-I: 15 (4.7)). 5 Pr-I and 4 Po-I patients required ketamine infusions, with 1 Pr-I patient also requiring IV lignocaine. CONCLUSIONS: Use of Buprenorphine via transdermal, sublingual and intravenous Patient Controlled Analgesia (PCA) delivery as part of an analgesic protocol for severe post stem cell transplant oral mucositis in adult patients appears to significantly reduce opioid requirements and pain on swallowing. Further randomised prospective work is required to confirm these associations.

Complete opioid transition to sublingual Buprenorphine after abdominal surgery is associated with significant reductions in opioid requirements, but not reduction in hospital length of stay: a retrospective cohort study.

BACKGROUND: The use of sublingual buprenorphine (SLBup) for acute pain after major abdominal surgery may offer the potential advantages of unique analgesic properties and more reliable absorption during resolving ileus. We hypothesized that complete opioid transition to SLBup rather than oral oxycodone (OOxy) in the early postoperative period after major abdominal surgery would reduce hospital length of stay, and acute pain and total OMEDD (Oral Morphine Equivalent Daily Dose) requirements in the first 24 h from post-parenteral opioid transition. METHODS: We reviewed 146 patients who had undergone elective and emergency abdominal surgery under our quaternary referral centre's Upper Gastro-Intestinal and Colo-Rectal Surgical Units 6 months before and after the introduction of complete postoperative transition to sublingual buprenorphine, rather than oral oxycodone, in July 2017. Our primary endpoint was 24-hourly post-transition OMEDDs; secondary endpoints were 24-hourly post-transition Mean NRS-11 pain scores on movement (POM) and length of hospital stay (LOS). Univariate analysis and linear multivariate regression analyses were used to quantify effect size and identify surgical, patient & other analgesic factors associated with these outcome measures. RESULTS: Patients transitioning to SLBup had reduced 24-hourly post-transition OMEDD requirements on postoperative day 2 (POD) (26 mg less, p = 0.04) and NRS-11 POM at POD1 (0.7 NRS-11 units less, p = 0.01). When adjusting for patient, surgical and special analgesic factors, SLBup was associated with a similar reduction in OMEDDs (Unstandardised beta-coefficient -26 mg, p = 0.0001), but not NRS-11 POM (p = 0.47) or hospital LOS (p = 0.16). CONCLUSIONS: Our change of practice from use of OOxy to SLBup as primary transition opioid from patient-controlled analgesia delivered full opioid agonists was associated with a clinically significant decrease in 24-hourly post-parenteral opioid transition OMEDDs and improved NRS-11 POM, but without an association with hospital LOS after major abdominal surgery. Further prospective randomized work is required to confirm these observed associations and impact on other important patient-centred outcomes.

Intraoperative low tidal volume ventilation and the risk of ICD-10 coded delirium and the use for antipsychotic medications.

BACKGROUND: Low tidal volume (VT) ventilation and its associated increase in arterial carbon dioxide (PaCO2) may affect postoperative neurologic function. We aimed to test the hypothesis that intraoperative low VT ventilation affect the incidence of postoperative ICD-10 coded delirium and/or the need for antipsychotic medications. METHODS: This is a post-hoc analysis of a large randomized controlled trial evaluating low vs. conventional VT ventilation during major non-cardiothoracic, non-intracranial surgery. The primary outcome was the incidence of ICD-10 delirium and/or the use of antipsychotic medications during hospital stay, and the absolute difference with its 95% confidence interval (CI) was calculated. RESULTS: We studied 1206 patients (median age of 64 [55-72] years, 59.0% males, median ARISCAT of 26 [19-37], and 47.6% of ASA 3). ICD-10 coded delirium and /or antipsychotic medication use was diagnosed in 11.2% with similar incidence between low and conventional VT ventilation (11.1% vs. 11.3%; absolute difference, -0.24 [95%CI, -3.82 to 3.32]; p = 0.894). There was no interaction between allocation group and type of surgery. CONCLUSION: In adult patients undergoing major surgery, low VT ventilation was not associated with increased risk of ICD-10 delirium and/or the use of antipsychotic medications during hospital stay. TRIAL REGISTRATION: ANZCTR Identifier: ACTRN12614000790640 .

Lgr5+ pericentral hepatocytes are self-maintained in normal liver regeneration and susceptible to hepatocarcinogenesis.

Emerging evidence suggests that hepatocytes are primarily maintained by self-renewal during normal liver homeostasis, as well as in response to a wide variety of hepatic injuries. However, how hepatocytes in distinct anatomic locations within the liver lobule are replenished under homeostasis and injury-induced regeneration remains elusive. Using a newly developed bacterial artificial chromosome (BAC)-transgenic mouse model, we demonstrate that Lgr5 expression in the liver is restricted to a unique subset of hepatocytes most adjacent to the central veins. Genetic lineage tracing revealed that pericentral Lgr5+ hepatocytes have a long lifespan and mainly contribute to their own lineage maintenance during postnatal liver development and homeostasis. Remarkably, these hepatocytes also fuel the regeneration of their own lineage during the massive and rapid regeneration process following two-thirds partial hepatectomy. Moreover, Lgr5+ hepatocytes are found to be the main cellular origin of diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) and are highly susceptible to neoplastic transformation triggered by activation of Erbb pathway. Our findings establish an unexpected self-maintaining mode for a defined subset of hepatocytes during liver homeostasis and regeneration, and identify Lgr5+ pericentral hepatocytes as major cells of origin in HCC development.

Intra-operative ventilator mechanical power as a predictor of postoperative pulmonary complications in surgical patients: A secondary analysis of a randomised clinical trial.

BACKGROUND: Studies in critically ill patients suggest a relationship between mechanical power (an index of the energy delivered by the ventilator, which includes driving pressure, respiratory rate, tidal volume and inspiratory pressure) and complications. OBJECTIVE: We aimed to assess the association between intra-operative mechanical power and postoperative pulmonary complications (PPCs). DESIGN: Post hoc analysis of a large randomised clinical trial. SETTING: University-affiliated academic tertiary hospital in Melbourne, Australia, from February 2015 to February 2019. PATIENTS: Adult patients undergoing major noncardiothoracic, nonintracranial surgery. INTERVENTION: Dynamic mechanical power was calculated using the power equation adjusted by the respiratory system compliance (CRS). Multivariable models were used to assess the independent association between mechanical power and outcomes. MAIN OUTCOME MEASURES: The primary outcome was the incidence of PPCs within the first seven postoperative days. The secondary outcome was the incidence of acute respiratory failure. RESULTS: We studied 1156 patients (median age [IQR]: 64 [55 to 72] years, 59.5% men). Median mechanical power adjusted by CRS was 0.32 [0.22 to 0.51] (J min-1)/(ml cmH2O-1). A higher mechanical power was also independently associated with increased risk of PPCs [odds ratio (OR 1.34, 95% CI, 1.17 to 1.52); P < 0.001) and acute respiratory failure (OR 1.40, 95% CI, 1.21 to 1.61; P < 0.001). CONCLUSION: In patients receiving ventilation during major noncardiothoracic, nonintracranial surgery, exposure to a higher mechanical power was independently associated with an increased risk of PPCs and acute respiratory failure. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Registry no: 12614000790640.