An improved method for generating human spinal cord neural stem cells.

Neural stem cells have exhibited efficacy in pre-clinical models of spinal cord injury (SCI) and are on a translational path to human testing. We recently reported that neural stem cells must be driven to a spinal cord fate to optimize host axonal regeneration into sites of implantation in the injured spinal cord, where they subsequently form neural relays across the lesion that support significant functional improvement. We also reported methods of deriving and culturing human spinal cord neural stem cells derived from embryonic stem cells that can be sustained over serial high passage numbers in vitro, providing a potentially optimized cell source for human clinical trials. We now report further optimization of methods for deriving and sustaining cultures of human spinal cord neural stem cell lines that result in improved karyotypic stability while retaining anatomical efficacy in vivo. This development improves prospects for safe human translation.

Variability of fibrinolytic activity in pregnant patients exposed to tissue plasminogen activator: an in vitro study utilizing rotational thromboelastometry.

BACKGROUND: The investigation into the variability of fibrinolysis in obstetric patients is notably limited despite its relevance to postpartum hemorrhage. We investigate an in vitro model of fibrinolysis measured by rotational thromboelastrometry (ROTEM) in maternal blood samples with lysis stimulated by tissue plasminogen activator (tPA). METHODS: Written informed consent was obtained from 19 patients at term pregnancy during admission to the labor and delivery unit. Patients who were taking medication affecting coagulation were excluded. Tissue plasminogen activator was added to whole blood samples to a final concentration of 100 or 220 ng/mL prior to ROTEM testing. RESULTS: The addition of tPA produced high intra-individual fibrinolytic variability for clot firmness and lysis parameters. Patients responded differently to each tPA dose ranging from clot lysis within the range of 0 ng/mL tPA group to complete clot lysis. The coefficient of variation (CV) values for the 220 ng/mL tPA group were: EXTEM MCF 0.510, EXTEM LI30 1.601, FIBTEM MCF 0.349, FIBTEM LI30 2.097. CV values for the 100 ng/mL tPA group were: EXTEM MCF 0.144, EXTEM LI30 1.038, FIBTEM MCF 0.096, FIBTEM LI30 1.238. CONCLUSION: We demonstrate a wide range of fibrinolytic response in the obstetric population to exogeneous tPA. We found subgroups of patients that were very responsive to tPA and insensitive to tPA. This study represents a preliminary exploration into classifying the obstetric fibrinolytic phenotypes. Further research will integrate relevant coagulation factors to establish a predictive model for testing susceptibility to lysis that can be applied at the point of care.

Management of ruptured aneurysmal subarachnoid hemorrhage with multiple basilar trunk aneurysms using a flow-diverter stent: A case report.

Ruptured aneurysmal subarachnoid hemorrhage associated with multiple basilar trunk aneurysms represents a rare clinical condition. Endovascular intervention stands as the preferred therapeutic approach. We present the case of a 35-year-old patient with subarachnoid hemorrhage and three consecutive basilar trunk aneurysms. Utilizing a flow-diverter stent, we achieved simultaneous occlusion of all 3 aneurysms, performed 2 hours post dual antiplatelet therapy (comprising salicylic acid 300 mg and ticagrelor 180 mg). Sustained resistance to clopidogrel necessitated the subsequent 3 months, followed by single antiplatelet therapy. At the 1-month follow-up, the patient demonstrated a favorable clinical course, devoid of cerebral infarction, and evidenced unobstructed stent patency upon brain magnetic resonance imaging.

Phase II trial of domatinostat (4SC-202) in combination with avelumab in patients with previously treated advanced mismatch repair proficient oesophagogastric and colorectal adenocarcinoma: EMERGE.

BACKGROUND: Most oesophagogastric adenocarcinomas (OGAs) and colorectal cancers (CRCs) are mismatch repair proficient (MMRp), responding poorly to immune checkpoint inhibition. We evaluated the safety and efficacy of domatinostat (histone deacetylase inhibitor) plus avelumab (anti-PD-L1 antibody) in patients with previously treated inoperable, advanced/metastatic MMRp OGA and CRC. PATIENTS AND METHODS: Eligible patients were evaluated in a multicentre, open-label dose escalation/dose expansion phase II trial. In the escalation phase, patients received escalating doses of domatinostat [100 mg once daily (OD), 200 mg OD, 200 mg twice daily (BD)] orally for 14 days followed by continuous dosing plus avelumab 10 mg/kg administered intravenously 2-weekly (2qw) to determine the recommended phase II dose (RP2D). The trial expansion phase evaluated the best objective response rate (ORR) during 6 months by RECIST version 1.1 using a Simon two-stage optimal design with 2/9 and 1/10 responses required to proceed to stage 2 in the OGA and CRC cohorts, respectively. RESULTS: Patients (n = 40) were registered between February 2019 and October 2021. Patients in the dose escalation phase (n = 12) were evaluated to confirm the RP2D of domatinostat 200 mg BD plus avelumab 10 mg/kg. No dose-limiting toxicities were observed. Twenty-one patients were treated at the RP2D, 19 (9 OGA and 10 CRC) were assessable for the best ORR; 2 patients with CRC did not receive combination treatment and were not assessable for the primary endpoint analysis. Six patients were evaluated in the dose escalation and expansion phases. In the OGA cohort, the best ORR was 22.2% (95% one-sided confidence interval lower bound 4.1) and the median duration of disease control was 11.3 months (range 9.9-12.7 months). No responses were observed in the CRC cohort. No treatment-related grade 3-4 adverse events were reported at the RP2D. CONCLUSIONS: Responses in the OGA cohort met the criteria to expand to stage 2 of recruitment with an acceptable safety profile. There was insufficient signal in the CRC cohort to progress to stage 2. TRIAL REGISTRATION: NCT03812796 (registered 23rd January 2019).

A PTHrP Gradient Drives Mandibular Condylar Chondrogenesis via Runx2.

The mandibular condylar cartilage (MCC) is an essential component of the temporomandibular joint, which orchestrates the vertical growth of the mandibular ramus through endochondral ossification with distinctive modes of cell differentiation. Parathyroid hormone-related protein (PTHrP) is a master regulator of chondrogenesis; in the long bone epiphyseal growth plate, PTHrP expressed by resting zone chondrocytes promotes chondrocyte proliferation in the adjacent layer. However, how PTHrP regulates chondrogenesis in the MCC remains largely unclear. In this study, we used a Pthrp-mCherry knock-in reporter strain to map the localization of PTHrP+ cells in the MCC and define the function of PTHrP in the growing mandibular condyle. In the postnatal MCC of PthrpmCherry/+ mice, PTHrP-mCherry was specifically expressed by cells in the superficial layer immediately adjacent to RUNX2-expressing cells in the polymorphic layer. PTHrP ligands diffused across the polymorphic and chondrocyte layers where its cognate receptor PTH1R was abundantly expressed. We further analyzed the mandibular condyle of PthrpmCherry/mCherry mice lacking functional PTHrP protein (PTHrP-KO). At embryonic day (E) 18.5, the condylar process and MCC were significantly truncated in the PTHrP-KO mandible, which was associated with a significant reduction in cell proliferation across the polymorphic layer and a loss of SOX9+ cells in the chondrocyte layers. The PTHrP-KO MCC showed a transient increase in the number of Col10a1+ hypertrophic chondrocytes at E15.5, followed by a significant loss of these cells at E18.5, indicating that superficial layer-derived PTHrP prevents premature chondrocyte exhaustion in the MCC. The expression of Runx2, but not Sp7, was significantly reduced in the polymorphic layer of the PTHrP-KO MCC. Therefore, PTHrP released from cells in the superficial layer directly acts on cells in the polymorphic layer to promote proliferation of chondrocyte precursor cells and prevent their premature differentiation by maintaining Runx2 expression, revealing a unique PTHrP gradient-directed mechanism that regulates MCC chondrogenesis.

Functional Connectivity Analysis of Visually Evoked ERPs for Mild Cognitive Impairment: Pilot Study.

Mild cognitive impairment (MCI) is considered the early stage of Alzheimer's disease, characterized as mild memory loss. A novel method of functional connectivity (FC) analysis can be used to detect MCI before memory is significantly impaired allowing for preventative measures to be taken. FC examines interactions between EEG channels to grant insight on underlying neural networks and analyze the effects of MCI. Applying FC method of weighted phase lag index (wPLI) to P300 ERPs provided insight on the link between the pathology of Alzheimer's disease and cognitive loss. wPLI was analyzed per frequency band (θ, α, µ, ß) and by channel combination groups (intra-hemispheric short, intra-hemispheric long, inter-hemispheric short, inter-hemispheric long, transverse). MCI was found to have a statistically significant lower ΔwPLIP300 compared to normal controls in the µ intra-hemispheric short (p = 0.0286), µ intra-hemispheric long (p = 0.0477), µ inter-hemispheric short (p = 0.0018) and the α intra-hemispheric short (p = 0.0423). Results indicate a possible deficiency in the dorsal visual processing pathway among MCI subjects as well as an unbalanced coordination between the two hemispheres.

Microfluidic-based production of [68Ga]Ga-FAPI-46 and [68Ga]Ga-DOTA-TOC using the cassette-based iMiDEV™ microfluidic radiosynthesizer.

BACKGROUND: The demand for 68Ga-labeled radiotracers has significantly increased in the past decade, driven by the development of diversified imaging tracers, such as FAPI derivatives, PSMA-11, DOTA-TOC, and DOTA-TATE. These tracers have exhibited promising results in theranostic applications, fueling interest in exploring them for clinical use. Among these probes, 68Ga-labeled FAPI-46 and DOTA-TOC have emerged as key players due to their ability to diagnose a broad spectrum of cancers ([68Ga]Ga-FAPI-46) in late-phase studies, whereas [68Ga]Ga-DOTA-TOC is clinically approved for neuroendocrine tumors. To facilitate their production, we leveraged a microfluidic cassette-based iMiDEV radiosynthesizer, enabling the synthesis of [68Ga]Ga-FAPI-46 and [68Ga]Ga-DOTA-TOC based on a dose-on-demand (DOD) approach. RESULTS: Different mixing techniques were explored to influence radiochemical yield. We achieved decay-corrected yield of 44 ± 5% for [68Ga]Ga-FAPI-46 and 46 ± 7% for [68Ga]Ga-DOTA-TOC in approximately 30 min. The radiochemical purities (HPLC) of [68Ga]Ga-FAPI-46 and [68Ga]Ga-DOTA-TOC were 98.2 ± 0.2% and 98.4 ± 0.9%, respectively. All the quality control results complied with European Pharmacopoeia quality standards. We optimized various parameters, including 68Ga trapping and elution, cassette batches, passive mixing in the reactor, and solid-phase extraction (SPE) purification and formulation. The developed synthesis method reduced the amount of precursor and other chemicals required for synthesis compared to conventional radiosynthesizers. CONCLUSIONS: The microfluidic-based approach enabled the implementation of radiosynthesis of [68Ga]Ga-FAPI-46 and [68Ga]Ga-DOTA-TOC on the iMiDEV™ microfluidic module, paving the way for their use in preclinical and clinical applications. The microfluidic synthesis approach utilized 2-3 times less precursor than cassette-based conventional synthesis. The synthesis method was also successfully validated in a similar microfluidic iMiDEV module at a different research center for the synthesis of [68Ga]Ga-FAPI-46 with limited runs. Our study demonstrated the potential of microfluidic methods for efficient and reliable radiometal-based radiopharmaceutical synthesis, contributing valuable insights for future advancements in this field and paving the way for routine clinical applications in the near future.

Predictive performance of CHA2DS2-VASc-HS score and Framingham risk scores for coronary disease severity in ischemic heart disease patients with invasive coronary angiography.

OBJECTIVE: The objective of this study was to determine the predictive performance and compatibility of CHA2DS2-VASc-HS scores and Framingham risk scores (FRS) in patients with coronary angiography. PATIENTS AND METHODS: This cross-sectional analysis study enrolled 98 patients with ischemic heart disease who were indicated for invasive coronary angiography. Sensitivity and specificity were determined using the cut-off values of the ROC curve. The Gensini score was used to evaluate the correlation. RESULTS: The cut-off value of the Congestive heart failure, hypertension, age 75 years, diabetes mellitus, stroke, vascular disease, age 65-74 years, sex category - hyperlipidemia, smoking (CHA2DS2-VASc-HS) score was 2.5, and for FRS, it was 14.5. The area under the curve (95% CI) for the CHA2DS2-VASc-HS score and FRS were 0.76 (0.66, 0.85) and 0.80 (0.71, 0.85), respectively. For every 1-point increase in the CHA2DS2-VASc-HS score, the Gensini score increased by 0.44 (r = 0.56; R2 = 0.19, Beta = 0.44, p < 0.01), and the number of stenosis coronary branches increased by 0.55 (r = 0.56; R2 = 0.30, Beta = 0.55, p < 0.01). For every 10-point increase in FRS, the Gensini score increased by 3.8 (r = 0.57; R2 = 0.14, Beta = 0.38, p < 0.01), and the number of stenosis coronary branches increased by 5 (r = 0.53; R2 = 0.25, Beta = 0.5, p < 0.01). CONCLUSIONS: Our study demonstrated a high predictive performance of coronary artery injury using the CHA2DS2-VASc-HS score and Framingham risk scores. These scores could be applied in predicting ischemic heart disease in non-symptomatic cases where invasive coronary angiography is not indicated.

Impact of regional climate change on the mosquito vector Aedes albopictus in a tropical island environment: La Réunion.

The recent expansion of Aedes albopictus across continents in both tropical and temperate regions and the exponential growth of dengue cases over the past 50 years represent a significant risk to human health. Although climate change is not the only factor responsible for the increase and spread of dengue cases worldwide, it might increase the risk of disease transmission at global and regional scale. Here we show that regional and local variations in climate can induce differential impacts on the abundance of Ae. albopictus. We use the instructive example of Réunion Island with its varied climatic and environmental conditions and benefiting from the availability of meteorological, climatic, entomological and epidemiological data. Temperature and precipitation data based on regional climate model simulations (3 km × 3 km) are used as inputs to a mosquito population model for three different climate emission scenarios. Our objective is to study the impact of climate change on the life cycle dynamics of Ae. albopictus in the 2070-2100 time horizon. Our results show the joint influence of temperature and precipitation on Ae. albopictus abundance as a function of elevation and geographical subregion. At low-elevations areas, decreasing precipitation is expected to have a negative impact on environmental carrying capacity and, consequently, on Ae. albopictus abundance. At mid- and high-elevations, decreasing precipitation is expected to be counterbalanced by a significant warming, leading to faster development rates at all life stages, and consequently increasing the abundance of this important dengue vector in 2070-2100.

Group VII ethylene response factors, MtERF74 and MtERF75, sustain nitrogen fixation in Medicago truncatula microoxic nodules.

Group VII ethylene response factors (ERF-VII) are plant-specific transcription factors (TFs) known for their role in the activation of hypoxia-responsive genes under low oxygen stress but also in plant endogenous hypoxic niches. However, their function in the microaerophilic nitrogen-fixing nodules of legumes has not yet been investigated. We investigated regulation and the function of the two Medicago truncatula ERF-VII TFs (MtERF74 and MtERF75) in roots and nodules, MtERF74 and MtERF75 in response to hypoxia stress and during the nodulation process using an RNA interference strategy and targeted proteolysis of MtERF75. Knockdown of MtERF74 and MtERF75 partially blocked the induction of hypoxia-responsive genes in roots exposed to hypoxia stress. In addition, a significant reduction in nodulation capacity and nitrogen fixation activity was observed in mature nodules of double knockdown transgenic roots. Overall, the results indicate that MtERF74 and MtERF75 are involved in the induction of MtNR1 and Pgb1.1 expression for efficient Phytogb-nitric oxide respiration in the nodule.

A Southeast Asian collaborative Delphi consensus on surveying risk factors for head and neck cancer screening and prevention.

The objective of this study was to determine high value questions for early detection and prevention of head and neck cancer by querying content experts on patient risk factors relevant to local communities in Southeast Asia (i.e., Vietnam, Laos, China, and Singapore). The Delphi method was employed using three rounds of asynchronous surveying which included participants among five different collaborating medical centers. 60 total survey items were assessed for consensus defined by a priori measures on the relative level of value of these questions for use in head and neck cancer screening. 77% of items reached a consensus and no items were concluded to be of low value despite differences in conclusions regarding relative importance. Survey items focused on patient demographic information and physical examination were examined across variables such as expert department affiliation, academic designation, and years of experience and found to be without statistically significant differences. However, with consensus items related to social risk factors, it was determined that participants who had 15 or more years of experience or identified as otolaryngologists rated these items at a relatively lower value than their peers with less experience (p < 0.0001, p = 0.0017) or outside the field of otolaryngology (p = 0.0101). This study explicitly identifies patient variables to consider in head and neck cancer screening that have not previously been comprehensively or methodically assessed in current literature. Increasing awareness of these risk factors may benefit the design and implementation of future head and neck cancer early detection and prevention programs in Southeast Asia and beyond as well as positively impact head and neck cancer outcomes.

The position during urine sample collection from young precontinent children through a bag does not limit contamination rates: Results from a randomized controlled trial: Does infant position influence quality of urine collection?

AIM: Despite its limitation, bag collection is still widely used for a preliminary urine screening test in non-toilet-trained children suspected of febrile urinary tract infection. A previous study conducted by our group raised the hypothesis that the absence of direct contact between urine and the perinea during urine collection could limit urine contamination by perineal flora. The aim of this study was to evaluate the impact of the patient's position during urine collection (upright standing position versus free position) on the rate of contaminated urine samples in non-toilet-trained children with suspected febrile urinary tract infection. METHODS: This prospective, randomized, controlled study took place in seven pediatric emergency departments. Two groups were compared: the intervention group (infants held in an upright standing position during urination) and the control group (free position during urination). RESULTS: Among the 800 pediatric patients randomized to the study, 124 had a urine culture, 60 in the intervention group and 64 in the control group. Among the 124 urine cultures, 12 (9.7%) were contaminated: eight (13.3%) in the intervention group and four (6.3%) in the control group (p = 0.1824). CONCLUSION: The results show that the patient's position does not have a significant impact on the quality of urine samples collected by bag.

The interplay of chronic stress and genetic traits discriminates between patients suffering from multisomatoform disorder with pain as the leading symptom and matched controls.

OBJECTIVE: Somatoform disorders and functional somatic syndromes (FSS) with symptoms that are not sufficiently explained by physical or technical examination are among the most challenging underlying causes. Many different somatoform disorders and FSS have overlapping symptoms, often with pain as the most prevalent one, leading to a high burden of disease. The concept of multisomatoform disorder (MSD) has been developed to acknowledge that fact. We analyzed a group of 151 patients and 149 matched controls to identify interactions of genetic and environmental factors with a possible influence on the development of MSD. DESIGN: In a retrospective case-control study, we performed a statistical analysis on 151 patients and 149 matched controls using logistic regression and a Classification and Regression Tree (CART) analysis. RESULTS: The logistic regression analysis of genes and environmental factors demonstrated significant differences in the results of the Trier Inventory of Chronic Stress (TICS) questionnaire, the single nucleotide polymorphism rs1800955 of the dopamine receptor D4 and the single nucleotide polymorphism rs4818 of the enzyme catechol-O-methyltransferase between patients with MSD and healthy controls. The resulting decision tree of the CART analysis determined that the TICS questionnaire was able to differentiate patients and controls most accurately, followed by certain genotypes of the 5-hydroxytryptamine receptor 2A and a single nucleotide polymorphism of the enzyme catechol-O-methyltransferase. CONCLUSIONS: The results of the statistical analysis identified a gene-environmental interaction possibly leading to MSD. The resulting identifiers could be used as a reference to inform diagnostic algorithms to easier identify patients suffering from MSD.

A systematic review of the evidence on the effect of parental communication about health and health behaviours on children's health and wellbeing.

Parents report feeling unsure how best to talk with their children about sensitive health topics and may avoid such conversations; yet if children have questions or concerns about their health, talking to a parent could enhance their health and wellbeing. We investigated the effects of parental communications about health and health behaviours on children's health and wellbeing, and explored what strategies can encourage parents to communicate about health. We conducted a systematic review and narrative synthesis of research published between January 2008 and April 2020 from five databases. Of 14,007 articles identified, 16 met inclusion criteria focusing on five topics: diet and weight (n = 5), body image (n = 2), sexual health (n = 7), physical activity (n = 1) and bullying (n = 1). Positive child outcomes were associated with positive general parent-child communication characterised by warmth, openness and allowing children choice. Conversely, hostility, negative and inconsistent messaging were associated with poorer outcomes. Interventions to increase parent-child communication could be classified as providing single directive messages, media campaigns or intensive support. Single messages increased communication frequency; media campaigns and intensive interventions showed mixed outcomes. No differences in outcomes were found according to child's gender or socio-economic status. Generally, parents were less confident in initiating, rather than continuing, conversations and were more likely to initiate conversations when they felt they had good topic knowledge. While the relatively small, diverse sample limits the strength of these findings, this review provides provisional support for approaches to promote positive parent-child communication about health that are associated with better child health and wellbeing.

Translation of Prognostic and Pharmacodynamic Biomarkers from Trial to Non-trial Patients with Metastatic Castration-resistant Prostate Cancer Treated with Docetaxel.

AIMS: We conducted a pooled analysis of four randomised controlled trials and a non-trial retrospective dataset to study the changes in serum prostate-specific antigen (PSA) concentrations during treatment and its impact on survival in men treated with docetaxel for metastatic castration-resistant prostate cancer. We also compared the outcomes and pre-treatment prognostic factors between trial and non-trial patients. MATERIALS AND METHODS: Data were obtained from four randomised controlled trials and a non-trial cohort from a tertiary cancer centre. The PSA kinetics covariates chosen were absolute value (PSAT), best percentage change (BPCH) and tumour growth rate (K). The association between the covariates collected and overall survival was assessed within a Cox proportional hazards model. How well a covariate captured the difference between trial and non-trial patients was assessed by reporting on models with or without trial status as a covariate. RESULTS: We reviewed individual datasets of 2282 patients. The median overall survival for trial patients was 20.4 (95% confidence interval 19.6-22.2) months and for the non-trial cohort was 12.4 (10.7-14.7) months (P < 0.001). Of the pre-treatment factors, we found that only lactate dehydrogenase fully captured the difference in prognosis between the trial and non-trial cohorts. All PSA kinetic metrics appeared to be prognostic in both the trial and non-trial patients. However, the effect size was reduced in non-trial versus trial patients (interaction P < 0.001). Of the time-dependent covariates, we found that BPCH best captured the difference between trial and non-trial patient prognosis. CONCLUSIONS: The analysis presented here highlights how data from open-source trial databases can be combined with emerging clinical practice databases to assess differences between trial versus non-trial patients for particular treatments. These results highlight the importance of developing prognostic models using both pre-treatment and time-dependent biomarkers of new treatments.

Promoting the get healthy information and coaching service (GHS) in Australian-Chinese communities: facilitators and barriers.

Obesity and being overweight are major public health concerns that health coaching can assist people to manage through encouraging self-management and behaviour change. The Get Healthy Information and Coaching Service (GHS) is a telephone health coaching service in Australia that has effectively improved the health of the general population but has had less participation of culturally and linguistically diverse (CALD) populations. The Chinese population is the largest migrant group in Australia with increased risk of diabetes but had reduced access to the GHS program due to communication barriers. The GHS developed a pilot program for Chinese (Mandarin and Cantonese-speaking) communities using bilingual coaches and translated material to address these barriers. Qualitative research was undertaken with Chinese stakeholders (14 interviews) and 11 program participants from the group which had completed the program (2 focus groups in Mandarin and Cantonese) to understand their experiences and the success of promotional activities. This research does not contain the experiences of the people that withdrew from the program. The bilingual program was culturally and linguistically appropriate and addressed risk factors for chronic conditions. Participants formed positive relationships with bilingual coaches who they preferred to interpreters. They felt the program promoted healthy eating, weight and physical activity. Although Chinese stakeholders had concerns about participants' ability to goal set, participants said they met their health goals and were committed to the GHS program. Strategies to enhance the program included promoting the bilingual GHS to the communities and stakeholders. Factors to consider beyond language in adapting the program to the Australian Chinese communities include meeting the heterogenous needs of the older population, ensuring community engagement and addressing cultural beliefs and practices.

Obesity and being overweight are major public health concerns that health coaching can assist people to manage. The Get Healthy Information and Coaching Service (GHS) is a government telephone health coaching service that has improved the health of the general population but has had less participation of culturally and linguistically diverse populations. The Chinese population is the largest migrant group in Australia with increased risk of diabetes but had reduced access to the GHS program due to communication barriers. The GHS developed a pilot program for Chinese (Mandarin and Cantonese-speaking) communities using bilingual coaches and translated material. Findings from 14 interviews with Chinese stakeholders and two focus groups (in Mandarin and Cantonese) with program participants sought to understand their experiences and success of promotional activities. Results demonstrated the bilingual program was culturally and linguistically appropriate. Participants formed positive relationships with coaches and felt the service promoted healthy eating and weight, and physical activity. Although Chinese stakeholders had concerns about participants' cultural familiarity with goal setting and achieving long-term change, participants said that they met their goals and were committed to the program. Strategies to enhance the program will include promoting the bilingual GHS to the communities and stakeholders.

Effect of high-flow vs. low-flow nasal plus mouthguard oxygen therapy on hypoxaemia during sedation: a multicentre randomised controlled trial.

Whether high-flow vs. low-flow nasal oxygen reduces hypoxaemia for sedation during endoscopic retrograde cholangiopancreatography is currently unknown. In this multicentre trial, 132 patients ASA physical status 3 or higher, BMI > 30 kg.m-2 or with known or suspected obstructive sleep apnoea were randomly allocated to high-flow nasal oxygen up to 60 l.min-1 at 100% FI O2 or low-flow nasal oxygen at 4 l.min-1 . The low-flow nasal oxygen group also received oxygen at 4 l.min-1 through an oxygenating mouthguard, totalling 8 l.min-1 . Primary outcome was hypoxaemia, defined as Sp O2 < 90% regardless of duration. Hypoxaemia occurred in 7.7% (5/65) of patients with high-flow and 9.1% (6/66) with low-flow nasal oxygen (percentage point difference -1.4%, 95%CI -10.9 to 8.0; p = 0.77). Between the groups, there were no significant differences in frequency of hypoxaemic episodes; lowest Sp O2 ; peak transcutaneous carbon dioxide; hypercarbia (transcutaneous carbon dioxide > 2.66 kPa from baseline); requirement of chin lift/jaw thrust; nasopharyngeal airway insertion; bag-mask ventilation; or tracheal intubation. Following adjustment for duration of the procedure, the primary outcome remained non-significant. In high-risk patients undergoing endoscopic retrograde cholangiopancreatography, oxygen therapy with high-flow nasal oxygen did not reduce the rate of hypoxaemia, hypercarbia or the need for airway interventions, compared with combined oral and nasal low-flow oxygen.

Minimally invasive treatment of abdominal lymphocele: A review of contemporary options and how to approach them.

Lymphoceles are lymphatic fluid collections resulting from lymphatic vessel disruption after surgery or trauma. They are most often described following retroperitoneal surgeries such as cystectomies, prostatectomies, renal transplants, and gynecologic surgeries. Most lymphoceles are asymptomatic and resolve spontaneously without treatment. If persistent, they can become infected or exert mass effect on adjacent structures causing pain, urinary, or lower limb edema particularly for lymphoceles in the pelvis Symptomatic lymphoceles should be treated to relieve symptoms and prevent functional compromise of vital adjacent structures. Although surgery has been traditionally accepted as the gold standard treatment, advances in imaging and interventional technology allow for less invasive, percutaneous treatment. Available minimally invasive treatment options include percutaneous aspiration, catheter drainage, sclerotherapy, and lymphangiography with lymphatic embolization. A review of these treatment options and a suggested algorithm for managing lymphoceles is presented.

Dental defects in the primary dentition associated with hypophosphatasia from biallelic ALPL mutations.

ALPL encodes tissue-nonspecific alkaline phosphatase (TNAP), an enzyme expressed in bone, teeth, liver, and kidney. ALPL loss-of-function mutations cause hypophosphatasia (HPP), an inborn error-of-metabolism that produces skeletal and dental mineralization defects. Case reports describe widely varying dental phenotypes, making it unclear how HPP comparatively affects the three unique dental mineralized tissues: enamel, dentin, and cementum. We hypothesized that HPP affected all dental mineralized tissues and aimed to establish quantitative measurements of dental tissues in a subject with HPP. The female proband was diagnosed with HPP during childhood based on reduced alkaline phosphatase activity (ALP), mild rachitic skeletal effects, and premature primary tooth loss. The diagnosis was subsequently confirmed genetically by the presence of compound heterozygous ALPL mutations (exon 5: c.346G>A, p.A116T; exon 10: c.1077C>G, p.I359M). Dental defects in 8 prematurely exfoliated primary teeth were analyzed by high resolution micro-computed tomography (micro-CT) and histology. Similarities to the Alpl-/- mouse model of HPP were identified by additional analyses of murine dentoalveolar tissues. Primary teeth from the proband exhibited substantial remaining root structure compared to healthy control teeth. Enamel and dentin densities were not adversely affected in HPP vs. control teeth. However, analysis of discrete dentin regions revealed an approximate 10% reduction in the density of outer mantle dentin of HPP vs. control teeth. All 4 incisors and the molar lacked acellular cementum by micro-CT and histology, but surprisingly, 2 of 3 prematurely exfoliated canines exhibited apparently normal acellular cementum. Based on dentin findings in the proband's teeth, we examined dentoalveolar tissues in a mouse model of HPP, revealing that the delayed initiation of mineralization in the incisor mantle dentin was associated with a broader lack of circumpulpal dentin mineralization. This study describes a quantitative approach to measure effects of HPP on dental tissues. This approach has uncovered a previously unrecognized novel mantle dentin defect in HPP, as well as a surprising and variable cementum phenotype within the teeth from the same HPP subject.

Traumatic right atrial rupture bridge to definitive repair with extra-corporeal life support.

Cardiac injury secondary to non-penetrating trauma is more common than thought, albeit, the injury is usually minor and goes undiagnosed without significant sequelae in most cases. Blunt cardiac rupture is much rarer accounting for <0.05% of all trauma cases but lethal in most circumstances. We present a case report of a young trauma victim who presented with both right atrial rupture and traumatic atrial septal disruption (ASD) requiring extra-corporeal life support (ECLS) and surgical repair. Blunt cardiac trauma with chamber rupture and septal disruption is a devastating injury. Stopping the hemorrhage and using ECLS gave our patient time to stabilize before definitive management of her traumatic ASD.