Tumor-associated NK cells drive MDSC-mediated tumor immune tolerance through the IL-6/STAT3 axis.

Apart from their killer identity, natural killer (NK) cells have integral roles in shaping the tumor microenvironment. Through immune gene deconvolution, the present study revealed an interplay between NK cells and myeloid-derived suppressor cells (MDSCs) in nonresponders of immune checkpoint therapy. Given that the mechanisms governing the outcome of NK cell-to-myeloid cell interactions remain largely unknown, we sought to investigate the cross-talk between NK cells and suppressive myeloid cells. Upon contact with tumor-experienced NK cells, monocytes and neutrophils displayed increased expression of MDSC-related suppressive factors along with increased capacities to suppress T cells. These changes were accompanied by impaired antigen presentation by monocytes and increased ER stress response by neutrophils. In a cohort of patients with sarcoma and breast cancer, the production of interleukin-6 (IL-6) by tumor-infiltrating NK cells correlated with S100A8/9 and arginase-1 expression by MDSCs. At the same time, NK cell-derived IL-6 was associated with tumors with higher major histocompatibility complex class I expression, which we further validated with b2m-knockout (KO) tumor mice models. Similarly in syngeneic wild-type and IL-6 KO mouse models, we then demonstrated that the accumulation of MDSCs was influenced by the presence of such regulatory NK cells. Inhibition of the IL-6/signal transducer and activator of transcription 3 (STAT3) axis alleviated suppression of T cell responses, resulting in reduced tumor growth and metastatic dissemination. Together, these results characterize a critical NK cell-mediated mechanism that drives the development of MDSCs during tumor immune escape.

Dexmedetomidine for analgesia and sedation in newborn infants receiving mechanical ventilation.

BACKGROUND: Dexmedetomidine is a selective alpha-2 agonist with minimal impact on the haemodynamic profile. It is thought to be safer than morphine or stronger opioids, which are drugs currently used for analgesia and sedation in newborn infants. Dexmedetomidine is increasingly being used in children and infants despite not being licenced for analgesia in this group. OBJECTIVES: To determine the overall effectiveness and safety of dexmedetomidine for sedation and analgesia in newborn infants receiving mechanical ventilation compared with other non-opioids, opioids, or placebo. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, and two trial registries in September 2023. SELECTION CRITERIA: We planned to include randomised controlled trials (RCTs) and quasi-RCTs evaluating the effectiveness of dexmedetomidine compared with other non-opioids, opioids, or placebo for sedation and analgesia in neonates (aged under four weeks) requiring mechanical ventilation. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were level of sedation and level of analgesia. Our secondary outcomes included days on mechanical ventilation, number of infants requiring additional medication for sedation or analgesia (or both), hypotension, neonatal mortality, and neurodevelopmental outcomes. We planned to use GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We identified no eligible studies for inclusion. We identified four ongoing studies, two of which appear to be eligible for inclusion; they will compare dexmedetomidine with fentanyl in newborn infants requiring surgery. We listed the other two studies as awaiting classification pending assessment of full reports. One study will compare dexmedetomidine with morphine in asphyxiated newborns undergoing hypothermia, and the other (mixed population, age up to three years) will evaluate dexmedetomidine versus ketamine plus dexmedetomidine for echocardiography. The planned sample size of the four studies ranges from 40 to 200 neonates. Data from these studies may provide some evidence for dexmedetomidine efficacy and safety. AUTHORS' CONCLUSIONS: Despite the increasing use of dexmedetomidine, there is insufficient evidence supporting its routine use for analgesia and sedation in newborn infants on mechanical ventilation. Furthermore, data on dexmedetomidine safety are scarce, and there are no data available on its long-term effects. Future studies should address the efficacy, safety, and long-term effects of dexmedetomidine as a single drug therapy for sedation and analgesia in newborn infants.

A multimodal atlas of hepatocellular carcinoma reveals convergent evolutionary paths and 'bad apple' effect on clinical trajectory.

BACKGROUND & AIMS: Hepatocellular Carcinoma (HCC) is a highly fatal cancer characterized by high intra-tumor heterogeneity (ITH). A panoramic understanding of its tumor evolution, in relation to its clinical trajectory, may provide novel prognostic and treatment strategies. METHODS: Through the Asia-Pacific Hepatocellular Carcinoma (AHCC) trials group (NCT03267641), we recruited one of the largest prospective cohorts of HCC with over 600 whole genome and transcriptome samples from 123 treatment-naïve patients. RESULTS: Using a multi-region sampling approach, we revealed seven convergent genetic evolutionary paths governed by the early driver mutations, late copy number variations and viral integrations, which stratify patient clinical trajectories after surgical resection. Furthermore, such evolutionary paths shaped the molecular profiles, leading to distinct transcriptomic subtypes. Most significantly, although we found the coexistence of multiple transcriptomic subtypes within certain tumors, patient prognosis was best predicted by the most aggressive cell fraction of the tumor, rather than by overall degree of transcriptomic ITH level - a phenomenon we termed the 'bad apple' effect. Finally, we found that characteristics throughout early and late tumor evolution provide significant and complementary prognostic power in predicting patient survival. CONCLUSIONS: Taken together, our study generated a comprehensive landscape of evolutionary history for HCC and provided a rich multi-omics resource for understanding tumor heterogeneity and clinical trajectories. CLINICAL TRIAL NUMBER: NCT03267641 (Observational cohort) IMPACT AND IMPLICATIONS: This prospective study, utilizing comprehensive multi-sector, multi-omics sequencing and clinical data from surgically resected HCC, reveals critical insights into the role of tumor evolution and intra-tumor heterogeneity (ITH) in determining the prognosis of Hepatocellular Carcinoma (HCC). These findings are invaluable for oncology researchers and clinicians, as they underscore the influence of distinct evolutionary paths and the 'bad apple' effect, where the most aggressive tumor fraction dictates disease progression. These insights not only enhance prognostic accuracy post-surgical resection but also pave the way for developing personalized therapies tailored to specific tumor evolutionary and transcriptomic profiles. The co-existence of multiple sub-types within the same tumor prompts a re-appraisal of the utilities of depending on single samples to represent the entire tumor and suggests the need for clinical molecular imaging. This research thus marks a significant step forward in the clinical understanding and management of HCC, underscoring the importance of integrating tumor evolutionary dynamics and multi-omics biomarkers into therapeutic decision-making.

A metagenomics-based workflow for the detection and genomic characterization of GBS in raw freshwater fish.

The unexpected foodborne outbreak in Singapore in 2015 has accentuated Group B Streptococcus (GBS, Streptococcus agalactiae) sequence type 283 as an emerging foodborne pathogen transmitted via the consumption of contaminated raw freshwater fish. Isolation-based workflows utilizing conventional microbiological and whole-genome sequencing methods are commonly used to support biosurveillance efforts critical for the control management of this emerging foodborne pathogen. However, these isolation-based workflows tend to have relatively long turnaround times that hamper a timely response for implementing risk mitigation. To address this gap, we have developed a metagenomics-based workflow for the simultaneous detection and genomic characterization of GBS in raw freshwater fish. Notably, our validation results showed that this metagenomics-based workflow could achieve comparable accuracy and potentially better detection limits while halving the turnaround time (from 2 weeks to 5 days) relative to an isolation-based workflow. The metagenomics-based workflow was also successfully adapted for use on a portable long-read nanopore sequencer, demonstrating its potential applicability for real-time point-of-need testing. Using GBS in freshwater fish as an example, this work represents a proof-of-concept study that supports the feasibility and validity of metagenomics as a rapid and accurate test methodology for the detection and genomic characterization of foodborne pathogens in complex food matrices. IMPORTANCE: The need for a rapid and accurate food microbiological testing method is apparent for a timely and effective foodborne outbreak response. This is particularly relevant for emerging foodborne pathogens such as Group B Streptococcus (GBS) whose associated food safety risk might be undercharacterized. By using GBS in raw freshwater fish as a case example, this study describes the development of a metagenomics-based workflow for rapid food microbiological safety testing and surveillance. This study can inform as a working model for various foodborne pathogens in other complex food matrices, paving the way for future methodological development of metagenomics for food microbiological safety testing.

Weakly Confined Organic-Inorganic Halide Perovskite Quantum Dots as High-Purity Room-Temperature Single Photon Sources.

Colloidal perovskite quantum dots (PQDs) have emerged as highly promising single photon emitters for quantum information applications. Presently, most strategies have focused on leveraging quantum confinement to increase the nonradiative Auger recombination (AR) rate to enhance single-photon (SP) purity in all-inorganic CsPbBr3 QDs. However, this also increases the fluorescence intermittency. Achieving high SP purity and blinking mitigation simultaneously remains a significant challenge. Here, we transcend this limitation with room-temperature synthesized weakly confined hybrid organic-inorganic perovskite (HOIP) QDs. Superior single photon purity with a low g(2)(0) < 0.07 ± 0.03 and a nearly blinking-free behavior (ON-state fraction >95%) in 11 nm FAPbBr3 QDs are achieved at room temperature, attributed to their long exciton lifetimes (τX) and short biexciton lifetimes (τXX). The significance of the organic A-cation is further validated using the mixed-cation FAxCs1-xPbBr3. Theoretical calculations utilizing a combination of the Bethe-Salpeter (BSE) and k·p approaches point toward the modulation of the dielectric constants by the organic cations. Importantly, our findings provide valuable insights into an additional lever for engineering facile-synthesized room-temperature PQD single photon sources.

Orthostatic hypotension in Parkinson's disease: Sit-to-stand vs. supine-to-stand protocol and clinical correlates.

BACKGROUND: Screening for orthostatic hypotension (OH) is integral in Parkinson's disease (PD) management, yet evidence-based guidelines on best practice methods for diagnosing OH in PD are lacking. METHODS: We investigated the frequency and correlates of OH, symptomatic OH, and neurogenic OH, in a large consecutively recruited PD cohort (n = 318), and compared the diagnostic performance of the sit-to-stand vs. the supine-to-stand blood pressure (BP) test. We evaluated the utility of continuous BP monitoring and tilt table testing in patients with postural symptoms or falls who were undetected to have OH with clinic-based BP measurements. Disease severity, fluid intake, orthostatic and overactive bladder symptoms, falls, comorbidities and medication history were evaluated. RESULTS: Patients' mean age was 66.1 ± 9.5years, with mean disease duration 7.8 ± 5.5years. OH frequency was 35.8 % based on the supine-to-stand test. OH in PD was significantly associated with older age, lower body mass index, longer disease duration, worse motor, cognitive and overactive bladder symptoms and functional disabilities, falls, and lower fluid intake. A similar profile was seen with asymptomatic OH. Three quarters of OH were neurogenic, with the majority also having supine hypertension. The sit-to-stand test had a sensitivity of only 0.39. One quarter of patients were additionally diagnosed with OH during continuous BP monitoring. CONCLUSIONS: The sit-to-stand test substantially underdiagnoses OH in PD, with the important practice implication that supine-to-stand measurements may be preferred. Screening for OH is warranted even in asymptomatic patients. Adequate fluid intake, treatment of urinary dysfunction and falls prevention are important strategies in managing PD patients with OH.

Complex lumbosacral spinal cord lipomas: A longitudinal study on outcomes from a Singapore children's hospital.

BACKGROUND: Total/near-total resection (TR/NTR) of complex lumbosacral lipomas (CSL) is reported to be associated with better long-term functional outcomes and lower symptomatic re-tethering rates. We report our institutional experience for CSL resection in affected children. METHODS: This is a single-institution, retrospective study. Inclusion criteria consist of patients with CSL with dorsal, transitional and chaotic lipomas based on Pang et al's classification. The study population is divided into 2 groups: asymptomatic patients with a normal preoperative workup referred to as 'prophylactic intent' and 'therapeutic intent' for those with pre-existing neuro-urological symptoms. Primary aims are to review factors that affect post-operative clean intermittent catheterization (CIC), functional outcomes based on Necker functional score (NFS), and re-tethering rates. RESULTS: 122 patients were included from 2000 to 2021. There were 32 dorsal lipomas (26.2 %), 74 transitional lipomas (60.7 %), and 16 chaotic lipomas (13.1 %). 82 % patients achieved TR/NTR. Favourable NFS at 1-year was 48.2 %. The re-tethering rate was 6.6 %. After multivariable analysis, post-operative CIC was associated with median age at surgery (p = 0.026), lipoma type (p = 0.029), conus height (p = 0.048) and prophylactic intent (p < 0.001). Next, extent of lipoma resection (p = 0.012) and the post-operative CSF leak (p = 0.004) were associated with re-tethering. Favourable NFS was associated with lipoma type (p = 0.047) and prophylactic intent surgery (p < 0.001). CONCLUSIONS: Our experience shows that TR/NTR for CSL is a feasible option to prevent functional deterioration and re-tethering. Efforts are needed to work on factors associated with post-operative CIC.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in New Zealand: peri-operative outcomes and service development over a decade.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is the standard of care for selected cases of peritoneal surface malignancy. However, due to its morbidity and learning curve, it is only delivered in six centres in Australia and Aotearoa New Zealand (AoNZ). In this study, we report peri-operative morbidity and mortality following CRS/HIPEC at Waikato and Braemar Hospitals, which have treated patients from all regions of AoNZ since 2008. METHODS: We retrospectively reviewed a database of all patients undergoing CRS and HIPEC from 01/01/2008 to 01/11/2020 at Waikato and Braemar Hospitals. RESULTS: Two-hundred and forty procedures were performed for 221 patients with a mean age of 55, including 22 (9.2%) re-do procedures. One hundred and eighty-six cases were European, 32 were Maori, and 16 were Pasifika. There were 152 pseudomyxoma peritonei, 39 colorectal adenocarcinomas, 29 appendiceal cancers, 8 ovarian cancers, 6 peritoneal mesothelioma, and 6 other tumour types. The median PCI was 16. HIPEC was administered to 196 out of 196 CC0/1 cases (100%) and 3 out of 44 CC2/3 cases (6.8%). Fifty-six cases (23.3%) had at least one major complication. There were two mortalities (0.8%) within 30 days. The median length of stay was 11 days. Operative duration was identified as an independent risk factor for major complications. There was considerable variation in the number of referrals from different regions of AoNZ. Over time, a decline in major complication rate is seen with increased case volume. CONCLUSION: The Waikato region has achieved favourable short-term outcomes following CRS/HIPEC.

Selective dorsal rhizotomy using a 3D high definition exoscope.

Selective dorsal rhizotomy (SDR) is an established neurosurgical technique for children with spastic diplegia secondary to cerebral palsy. Meticulous intraoperative testing of individual nerve roots with electromyography in tandem with the on-site neurorehabilitation team is recommended for good clinical outcomes. The standard approach requires the neurosurgeons to spend extended time under the traditional operating microscope. In this video, the authors describe the use of a 3D exoscope system for SDR. Overall, the 3D exoscope improves ergonomics and reduces musculoskeletal fatigue for the operating neurosurgeons. Furthermore, it provides excellent visualization of important structures, allowing safe and efficient completion of the procedure. The video can be found here: https://stream.cadmore.media/r10.3171/2023.10.FOCVID23105.

Validity and reliability of the Malay language Perception Towards Smoking Questionnaire (BM-PTSQ) among secondary school adolescents: Further validation using Confirmatory Factor Analysis.

INTRODUCTION: Perception is an essential factor influencing smoking among adolescents. Thus, a valid tool for measuring perception is a requisite in smoking studies. This study further establishes the validity and reliability of a Malay language version of the Perception Towards Smoking Questionnaire (BM-PTSQ) for assessing the perception of smoking among secondary school-going adolescents in Malaysia. METHODS: We administered the BM-PTSQ to 669 secondary school students selected through multistage sampling; 60% of respondents were male (n=398), and 69.9% (n=463) were from rural areas. Respondents were aged 13-16 years, 36.4% (n=241) were 13 years, 40.0% (n=265) were 14 years, and 23.6% (n=156) were 16 years old. We used parallel and exploratory factor analysis (EFA) to determine the domains of the questionnaire. In addition, we also employed EFA, confirmatory factor analyses (CFA), and Cronbach's alpha to evaluate the construct validity and reliability of the BM-PTSQ. RESULTS: EFA and parallel analysis identified two domains in the BM-PTSQ that accounted for 62.9% of the observed variance, and CFA confirmed the two-domain structure. The two domains' internal consistency scores ranged from 0.702 to 0.80, which suggested adequate reliability. CONCLUSIONS: The BM-PTSQ has acceptable psychometric validity and is appropriate for assessing smoking perception and intention among Malaysian secondary school-aged youth. Researchers should further evaluate this tool's applicability in a more sociodemographically diverse population.

Loss-of-Function Variant in the SMPD1 Gene in Progressive Supranuclear Palsy-Richardson Syndrome Patients of Chinese Ancestry.

Lysosomal dysfunction plays an important role in neurodegenerative diseases, including Parkinson's disease (PD) and possibly Parkinson-plus syndromes such as progressive supranuclear palsy (PSP). This role is exemplified by the involvement of variants in the GBA1 gene, which results in a deficiency of the lysosomal enzyme glucocerebrosidase and is the most frequently identified genetic factor underlying PD worldwide. Pathogenic variants in the SMPD1 gene are a recessive cause of Niemann-Pick disease types A and B. Here, we provide the first report on an association between a loss-of-function variant in the SMPD1 gene present in a heterozygous state (p.Pro332Arg/p.P332R, which is known to result in reduced lysosomal acid sphingomyelinase activity), with PSP-Richardson syndrome in three unrelated patients of Chinese ancestry.

Nonclassical Crystal Growth of Supramolecular Polymers in Aqueous Medium.

A mechanistic understanding of the principles governing the hierarchical organization of supramolecular polymers offers a paradigm for tailoring synthetic molecular architectures at the nano to micrometric scales. Herein, the unconventional crystal growth mechanism of a supramolecular polymer of superbenzene(coronene)-diphenylalanine conjugate (Cr-FFOEt ) is demonstrated. 3D electron diffraction (3D ED), a technique underexplored in supramolecular chemistry, is effectively utilized to gain a molecular-level understanding of the gradual growth of the initially formed poorly crystalline hairy, fibril-like supramolecular polymers into the ribbon-like crystallites. The further evolution of these nanosized flat ribbons into microcrystals by oriented attachment and lateral fusion is probed by time-resolved microscopy and electron diffraction. The gradual morphological and structural changes reveal the nonclassical crystal growth pathway, where the balance of strong and weak intermolecular interactions led to a structure beyond the nanoscale. The role of distinct π-stacking and H-bonding interactions that drive the nonclassical crystallization process of Cr-FFOEt supramolecular polymers is analyzed in comparison to analogous molecules, Py-FFOEt and Cr-FF forming helical and twisted fibers, respectively. Furthermore, the Cr-FFOEt crystals formed through nonclassical crystallization are found to improve the functional properties.

Long-term survival following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in Waikato, Aotearoa New Zealand: a 12-year experience.

BACKGROUNDS: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have improved survival for selected cases of peritoneal surface malignancy. In 2008, a CRS/HIPEC service was first established in Aotearoa New Zealand (AoNZ) at Waikato and Braemar Hospitals in the Waikato region. METHODS: This is a retrospective review of a prospectively maintained database of all patients undergoing CRS/HIPEC from 1 January 2008 to 1 November 2020 at Waikato and Braemar Hospitals. We analysed long-term survival and predictors of survival for each tumour type. RESULTS: 240 procedures were performed for 221 patients, including 22 re-do procedures. Cases had a median peritoneal cancer index of 16. Complete cytoreduction (CC0-1) was achieved in 196 cases (81.7%). All complete cytoreduction cases received HIPEC. There were 152 pseudomyxoma peritonei (PMP), 39 colorectal cancers (CRC), 29 appendiceal cancers, eight ovarian cancers, six peritoneal mesotheliomas, and six other cancers. The 5-year overall survival (OS) for PMP with acellular mucin, low-grade mucinous carcinoma peritonei, and high-grade mucinous carcinoma peritonei with or without signet cells were 91.6%, 80.5%, and 72.2%, respectively. 2- and 5-year OS in CRC were 56.7% and 40.4%. The achievement of complete cytoreduction improved the 5-year OS to 87.9% across all PMP and 45.1% in colorectal cancer. Incomplete cytoreduction predicted worse survival in appendiceal PMP. In colorectal cancer, worse survival was predicted in those who had incomplete cytoreduction, liver metastasis, and presentation with obstruction and perforation. CONCLUSION: Favourable long-term outcomes following CRS/HIPEC for peritoneal surface malignancy have been achieved in AoNZ through the Waikato peritonectomy service.

Evaluation of the microbiological efficacy of cleaning agents for tracheostomy inner cannulas.

PURPOSE: Biofilms are a significant cause of morbidity in patients with indwelling medical devices. Biofilms pose a potential risk with reusable inner cannulas by increasing the risk of infections. Effective decontamination is thus vital in decreasing bioburden. The current guidelines for cleaning inner cannulas are varied, with multiple techniques being recommended, which are not supported by strong evidence. This randomized, controlled, cross-over study attempted to enumerate the bacterial count of inner cannulas used in tracheostomy patients (n = 60) pre-and post-decontamination with detergent (A) or sterile water (B). MATERIALS AND METHODS: The patients were randomly allocated to sequence A > B or B > A in 1:1 fashion. The saline flushing of the inner cannulas was plated on trypticase soy agar with 5 % sheep blood to enumerate the bacterial count. RESULTS: The mean ratio [Log (CFU)post/Log (CFU)pre]A/[Log (CFU)post/Log (CFU)pre]B based on 53 samples was 0.918 ± 0.470, two-sided 90 % confidence interval (CI) 0.812, 1.024. The equivalence criterion was met as the mean ratio after cleaning fell within the equivalence region of 0.8 and 1.25. CONCLUSION: This study demonstrated the microbiological efficacy of both detergent and sterile water in the decontamination of inner cannulas, and that sterile water was not less effective than detergent in reducing the bacterial load for safe re-use of inner cannulas. This has the potential to promote cost savings for patients with tracheostomy, both in the hospital and the community. The study findings may also be relevant in formulating tracheostomy care policies.

Traumatic cavernous sinus syndrome - A peculiar presentation of multiple cranial nerve neuropathies following a minor head injury: Case report and literature review.

BACKGROUND: In patients with traumatic head injuries, the percentage of cranial nerve injuries (CNI) range from4.3 to 17.6% in which majority are isolated CNI[1-5].In present literature, moderate to severe types of head injuries are often studied which may result in a lack of representation and description of CNI associated with minor head injuries (MHI). Alongside this peculiar case of a traumatic cavernous sinus syndrome (CSS) that is non-thrombotic and non-fistulous in nature, this paper aims to analyse traumatic CNI in non-severe head injuries and the surrounding literature. CASE REPORT: A 65-year-old man who had sustained a minor head injury was found to have CNI of III, IV and VI.Brain imaging showed scattered traumatic subarachnoid haemorrhage and a non-displaced right zygomatic arch fracture. Despite the short course of high dose dexamethasone, he showed only partial recovery of his CNI after one year. CONCLUSION: We present a case of traumatic CSS likely secondary to tractional injury from a MHI. Injury to the extraocular nerves wasfound to be one of the more commonly observed combination of CNI from the literature review conducted. In patients with MHI, multiple CNI is less common. Hence, consideration should be given to work upfor secondary causes such as tumours. There is presently no known clear identifiable pattern of CNI associated with MHI. CT brain findings of skull base fractures and early onset of cranial nerve palsies are generally associated with worse outcomes. More remains to be studied about tractional CNI in non-severe head injuries.

Intra-pancreatic fat is associated with high circulating glucagon and GLP-1 concentrations following whey protein ingestion in overweight women with impaired fasting glucose: A randomised controlled trial.

AIM: Intra-pancreatic fat deposition (IPFD) while hypothesised to impair beta-cell function, its impact on alpha-cells remains unclear. We evaluated the association between IPFD and markers of pancreatic cells function using whey protein. METHODS: Twenty overweight women with impaired fasting glucose (IFG) and low or high IPFD (<4.66% vs ≥4.66%) consumed 3 beverage treatments: 0 g (water control), 12.5 g (low-dose) and 50.0 g (high-dose) whey protein, after an overnight fast, in randomised order. Blood glucose, insulin, C-peptide, glucagon, gastric-inhibitory polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and amylin were analysed postprandially over 4 h. Incremental area-under-the-curve (iAUC), incremental maximum concentration (iCmax), and time to maximum concentration (Tmax) for these were compared between IPFD groups using repeated measures linear mixed models, also controlled for age (pcov). RESULTS: iAUC and iCmax glucose and insulin while similar between the two IPFD groups, high IPFD and ageing contributed to higher postprandial glucagon (iAUC: p = 0.012; pcov = 0.004; iCmax: p = 0.069; pcov = 0.021) and GLP-1 (iAUC: p = 0.006; pcov = 0.064; iCmax: p = 0.011; pcov = 0.122) concentrations. CONCLUSION: In our cohort, there was no evidence that IPFD impaired protein-induced insulin secretion. Conversely, IPFD may be associated with increased protein-induced glucagon secretion, a novel observation which warrants further investigation into its relevance in the pathogenesis of dysglycaemia and type-2 diabetes.

Making and Breaking of Exciton Cooling Bottlenecks in Halide Perovskite Nanocrystals.

Harnessing quantum confinement (QC) effects in semiconductors to retard hot carrier cooling (HCC) is an attractive approach for enabling efficient hot carrier extraction to overcome the Shockley-Queisser limit. However, there is a debate about whether halide perovskite nanocrystals (PNCs) can effectively exploit these effects. To address this, we utilized pump-probe and multipulse pump-push-probe spectroscopy to investigate HCC behavior in PNCs of varying sizes and cation compositions. Our results validate the presence of an intrinsic phonon bottleneck with clear manifestations of QC effects in small CsPbBr3 PNCs exhibiting slower HCC rates compared to those of larger PNCs. However, the replacement of inorganic Cs+ with organic cations suppresses this intrinsic bottleneck. Furthermore, PNCs exhibit distinct size-dependent HCC behavior in response to changes in the cold carrier densities. We attribute this to the enhanced exciton-exciton interactions in strongly confined PNCs that facilitate Auger heating. Importantly, our findings dispel the existing controversy and provide valuable insights into design principles for engineering QC effects in PNC hot carrier applications.

Bridging science and accessibility: a tactile journey from gluten through to coeliac disease.

As part of the Monash Sensory Science Exhibition, our team guided participants through a multisensory journey unraveling coeliac disease development and pathology. Through tactile and sensory exhibits, we showed how benign dietary gluten can be transformed into a harmful entity for the 1 in 70 Australians with this illness. In contrast to the common misconception of coeliac disease as a food allergy, our exhibits revealed its closer association with autoimmune diseases such as type 1 diabetes, involving genetic susceptibility linked to specific human leukocyte antigens, crucial antigen-specific T- and B-cell responses and autoantibody production. Tactile models underscored the severe consequences of the proinflammatory immune response to gluten on patient health and quality of life. This educational event affirmed to us the value and importance of fostering inclusivity in science education.

Controlling the Assembly of Cellulose-Based Oligosaccharides through Sequence Modifications.

Peptides and nucleic acids with programmable sequences are widely explored for the production of tunable, self-assembling functional materials. Herein we demonstrate that the primary sequence of oligosaccharides can be designed to access materials with tunable shapes and properties. Synthetic cellulose-based oligomers were assembled into 2D or 3D rod-like crystallites. Sequence modifications within the oligosaccharide core influenced the molecular packing and led to the formation of square-like assemblies based on the rare cellulose IVII allomorph. In contrast, modifications at the termini generated elongated aggregates with tunable surfaces, resulting in self-healing supramolecular hydrogels.

Carrier multiplication in perovskite solar cells with internal quantum efficiency exceeding 100.

Carrier multiplication (CM) holds great promise to break the Shockley-Queisser limit of single junction photovoltaic cells. Despite compelling spectroscopic evidence of strong CM effects in halide perovskites, studies in actual perovskite solar cells (PSCs) are lacking. Herein, we reconcile this knowledge gap using the testbed Cs0.05FA0.5MA0.45Pb0.5Sn0.5I3 system exhibiting efficient CM with a low threshold of 2Eg (~500 nm) and high efficiency of 99.4 ± 0.4%. Robust CM enables an unbiased internal quantum efficiency exceeding 110% and reaching as high as 160% in the best devices. Importantly, our findings inject fresh insights into the complex interplay of various factors (optical and parasitic absorption losses, charge recombination and extraction losses, etc.) undermining CM contributions to the overall performance. Surprisingly, CM effects may already exist in mixed Pb-Sn PSCs but are repressed by its present architecture. A comprehensive redesign of the existing device configuration is needed to leverage CM effects for next-generation PSCs.