Fracture of the Proximal Body of a Modern Cementless Modular Fluted Tapered Stem.

Previous reports have described failures of modular fluted tapered femoral stems secondary to fatigue failure at the modular junction. However, the present study is the first reported case of modular fluted tapered femoral component failure involving atraumatic fracture of the proximal body following revision total hip arthroplasty. The failure occurred in a 52-year-old female with a history of postmenopausal osteoporosis on bisphosphonates who sustained an atraumatic fracture of the proximal body of a modular revision femoral stem. In the present case, revision THA utilizing a wider proximal body segment with proximal augmentation using strut allografts for biological and mechanical support provided the patient with a stable construct at 30-month follow-up.

Single-Cell Transcriptomic Profiling of Cholangiocyte Organoids Derived from Bile Ducts of Primary Sclerosing Cholangitis Patients.

BACKGROUND AND AIMS: Primary sclerosing cholangitis (PSC) is a chronic inflammatory liver disorder without effective medical treatment which is characterized by inflammation and fibrotic structures around the bile ducts. Biliary epithelial cells (cholangiocytes) are the target and potential disease drivers in PSC, yet little is known if cholangiocytes from PSC patients differ from non-PSC controls. To characterize cholangiocytes at early rather than end-stage disease, cholangiocyte organoids (COs) were derived from diseased bile ducts of PSC patients and compared to organoids generated from disease controls. METHODS: Cholangiocytes were obtained during endoscopic retrograde cholangiopancreatography (ERCP) brushing of diseased bile duct areas and expanded as organoids using previously established culture methods. Stable CO lines were analyzed for cell type identity, basic cholangiocyte function, and transcriptomic signature. RESULTS: We demonstrate that cholangiocytes, derived from the damaged area within the bile ducts of PSC patients, can be expanded in culture without displaying functional or genetic disease-related features. We further show that COs from patients who later were diagnosed with dysplasia exhibit higher expression of the cancer-associated genes PGC, FXYD2, MIR4435-2HG, and HES1. CONCLUSIONS: Our results demonstrate that PSC organoids are largely similar to control organoids after culture and highlight the significance of COs as a tool for regenerative medicine approaches as well as their potential for discovering new potential biomarkers for diagnosing cholangiocarcinoma.

PSMF1 variants cause a phenotypic spectrum from early-onset Parkinson's disease to perinatal lethality by disrupting mitochondrial pathways.

Dissecting biological pathways highlighted by Mendelian gene discovery has provided critical insights into the pathogenesis of Parkinson's disease (PD) and neurodegeneration. This approach ultimately catalyzes the identification of potential biomarkers and therapeutic targets. Here, we identify PSMF1 as a new gene implicated in PD and childhood neurodegeneration. We find that biallelic PSMF1 missense and loss-of-function variants co-segregate with phenotypes from early-onset PD and parkinsonism to perinatal lethality with neurological manifestations across 15 unrelated pedigrees with 22 affected subjects, showing clear genotype-phenotype correlation. PSMF1 encodes the proteasome regulator PSMF1/PI31, a highly conserved, ubiquitously expressed partner of the 20S proteasome and neurodegeneration-associated F-box-O 7 and valosin-containing proteins. We demonstrate that PSMF1 variants impair mitochondrial membrane potential, dynamics and mitophagy in patient-derived fibroblasts. Additionally, we develop models of psmf1 knockdown Drosophila and Psmf1 conditional knockout mouse exhibiting age-dependent motor impairment, with diffuse gliosis in mice. These findings unequivocally link defective PSMF1 to early-onset PD and neurodegeneration and suggest mitochondrial dysfunction as a mechanistic contributor.

Trabecular Metal Augments During Complex Primary Total Hip Arthroplasty.

Background: Trabecular metal augments (TMAs) have been extensively used in revision total hip arthroplasty (THA) to address acetabular bone defects. However, limited data exists regarding TMA utilization during primary THA. This study aims to assess the clinical and radiographic outcomes of TMAs used during primary THA. Methods: A single-institution retrospective case series of primary THA patients treated with TMA between 2010 and 2019 was performed. Patient demographics, complications, and revisions were recorded. Cup position, center of rotation, leg length, and radiolucent lines were assessed radiographically. The Kaplan-Meier method was used to compute implant survivorship. Results: Twenty-six patients (30 hips) were included with average age of 52.6 ± 15.3 years (range: 22-78) and mean follow-up of 4.1 ± 2.1 years (range: 2.0-8.9). Most TMAs were indicated for developmental dysplasia of the hip (n = 18; 60.0%). On average, hip center of rotation was lowered 1.5 ± 1.3 cm and lateralized 1.2 ± 1.5 cm, while leg length and global offset were increased by 2.4 ± 1.2 cm and 0.4 ± 1.0 cm, respectively. At final follow-up, 3 hips (10.0%) required revision: one (3.3%) for aseptic loosening and 2 (6.7%) for instability. No patients had progressive radiolucent lines at final follow-up. Five-year survival with aseptic loosening and all-cause revision as endpoints was 100% (95% confidence interval: 90.0%-100.0%) and 92.1% (95% confidence interval: 81.3%-100.0%), respectively. One patient required revision for aseptic loosening after the 5-year mark. Conclusions: Trabecular metal augmentation during primary THA demonstrates satisfactory early to mid-term outcomes. TMA is a viable option for complex primary THA when bone loss is encountered or secondary support is required. Level of Evidence: Level IV.

Super-Obesity is Associated With an Increased Risk of Complications Following Primary Total Knee Arthroplasty.

BACKGROUND: Obesity, defined as a body mass index (BMI) ≥ 30, is an ever-growing epidemic, with > 35% of adults in the United States currently classified as obese. Super-obese individuals, defined as those who have a BMI ≥ 50, are the fastest-growing portion of this group. This study sought to quantify the infection risk as well as the incidence of surgical, medical, and thromboembolic complications among super-obese patients undergoing total knee arthroplasty (TKA). METHODS: An all-payer claims database was used to identify patients who underwent elective, primary TKA between 2016 and 2021. Patients who had a BMI ≥ 50 were compared to those who had a normal BMI of 18 to 25. Demographics and the incidence of 90-days postoperative complications were compared between the 2 groups. Univariate analysis and multivariable regression were used to assess differences between groups. RESULTS: In total, 3,376 super-obese TKA patients were identified and compared to 17,659 patients who had a normal BMI. Multivariable analysis indicated that the super-obese cohort was at an increased postoperative risk of periprosthetic joint infection (adjusted odds ratio [aOR] 3.7, 95% confidence interval [CI]: 2.1 to 6.4, P < .001), pulmonary embolism (aOR 2.2, 95%-CI: 1.0 to 5.0, P = .047), acute respiratory failure (aOR 4.1, 95%-CI: 2.7 to 6.1, P < .001), myocardial infarction (aOR 2.5, 95%-CI: 1.1 to 5.8, P = .026), wound dehiscence (aOR 2.3, 95%-CI: 1.4 to 3.8, P = .001), and acute renal failure (aOR 3.2, 95%-CI: 2.4 to 4.2, P < .001) relative to patients who have normal BMI. CONCLUSIONS: Super-obese TKA patients are at an elevated risk of postoperative infectious, surgical, medical, and thromboembolic complications. As such, risk stratification, as well as appropriate medical management and optimization, is of utmost importance for this high-risk group.

Whole genome sequencing in paediatric channelopathy and cardiomyopathy.

Background: Precision medicine in paediatric cardiac channelopathy and cardiomyopathy has a rapid advancement over the past years. Compared to conventional gene panel and exome-based testing, whole genome sequencing (WGS) offers additional coverage at the promoter, intronic regions and the mitochondrial genome. However, the data on use of WGS to evaluate the genetic cause of these cardiovascular conditions in children and adolescents are limited. Methods: In a tertiary paediatric cardiology center, we recruited all patients diagnosed with cardiac channelopathy and cardiomyopathy between the ages of 0 and 18 years old, who had negative genetic findings with prior gene panel or exome-based testing. After genetic counselling, blood samples were collected from the subjects and both their parents for WGS analysis. Results: A total of 31 patients (11 cardiac channelopathy and 20 cardiomyopathy) were recruited. Four intronic splice-site variants were identified in three cardiomyopathy patients, which were not identified in previous whole exome sequencing. These included a pathogenic variant in TAFAZZIN:c.284+5G>A (Barth syndrome), a variant of unknown significance (VUS) in MYBPC3:c.1224-80G>A and 2 compound heterozygous LP variants in LZTR1 (LZTR1:c.1943-256C>T and LZTR1:c1261-3C>G) in a patient with clinical features of RASopathy. There was an additional diagnostic yield of 1.94% using WGS for identification of intronic variants, on top of conventional gene testing. Conclusion: WGS plays a role in identifying additional intronic splice-site variants in paediatric patients with isolated cardiomyopathy. With the demonstrated low extra yield of WGS albeit its ability to provide potential clinically important information, WGS should be considered in selected paediatric cases of cardiac channelopathy and cardiomyopathy in a cost-effective manner.

Prioritize Variant Reclassification in Pediatric Long QT Syndrome-Time to Revisit.

Congenital long QT syndrome (LQTS) is an inherited arrhythmia syndrome associated with sudden cardiac death. Accurate interpretation and classification of genetic variants in LQTS patients are crucial for effective management. All patients with LQTS with a positive genetic test over the past 18 years (2002-2020) in our single tertiary pediatric cardiac center were identified. Reevaluation of the reported variants in LQTS genes was conducted using the American College of Genetics and Genomics (ACMG) guideline after refinement by the US ClinGen SVI working group and guideline by Walsh et al. on genetic variant reclassification, under multidisciplinary input. Among the 59 variants identified. 18 variants (30.5%) were reclassified. A significant larger portion of variants of unknown significance (VUS) were reclassified compared to likely pathogenic (LP)/pathogenic (P) variants (57.7% vs 9.1%, p < 0.001). The rate of reclassification was significantly higher in the limited/disputed evidence group compared to the definite/moderate evidence group (p = 0.0006). All LP/P variants were downgraded in the limited/disputed evidence group (p = 0.0057). VUS upgrades are associated with VUS located in genes within the definite/moderate evidence group (p = 0.0403) and with VUS present in patients exhibiting higher corrected QT intervals (QTc) (p = 0.0445). A significant number of pediatric LQTS variants were reclassified, particularly for VUS. The strength of the gene-disease association of the genes influences the reclassification performance. The study provides important insights and guidance for pediatricians to seek for reclassification of "outdated variants" in order to facilitate contemporary precision medicine.

Revealing the role of SPP1+ macrophages in glioma prognosis and therapeutic targeting by investigating tumor-associated macrophage landscape in grade 2 and 3 gliomas.

BACKGROUND: Glioma is a highly heterogeneous brain tumor categorized into World Health Organization (WHO) grades 1-4 based on its malignancy. The suppressive immune microenvironment of glioma contributes significantly to unfavourable patient outcomes. However, the cellular composition and their complex interplays within the glioma environment remain poorly understood, and reliable prognostic markers remain elusive. Therefore, in-depth exploration of the tumor microenvironment (TME) and identification of predictive markers are crucial for improving the clinical management of glioma patients. RESULTS: Our analysis of single-cell RNA-sequencing data from glioma samples unveiled the immunosuppressive role of tumor-associated macrophages (TAMs), mediated through intricate interactions with tumor cells and lymphocytes. We also discovered the heterogeneity within TAMs, among which a group of suppressive TAMs named TAM-SPP1 demonstrated a significant association with Epidermal Growth Factor Receptor (EGFR) amplification, impaired T cell response and unfavourable patient survival outcomes. Furthermore, by leveraging genomic and transcriptomic data from The Cancer Genome Atlas (TCGA) dataset, two distinct molecular subtypes with a different constitution of TAMs, EGFR status and clinical outcomes were identified. Exploiting the molecular differences between these two subtypes, we developed a four-gene-based prognostic model. This model displayed strong associations with an elevated level of suppressive TAMs and could be used to predict anti-tumor immune response and prognosis in glioma patients. CONCLUSION: Our findings illuminated the molecular and cellular mechanisms that shape the immunosuppressive microenvironment in gliomas, providing novel insights into potential therapeutic targets. Furthermore, the developed prognostic model holds promise for predicting immunotherapy response and assisting in more precise risk stratification for glioma patients.

Simpson-Golabi-Behmel syndrome type 1 with normal birth parameters.

A newborn baby born at 34 weeks and 5 days gestation was admitted for prematurity, dysmorphic features and congenital heart defects. Antenatal scan at 21 weeks showed a large-for-gestational-age foetus with a large abdominal circumference and liver, ventricular septal defect, right prominent renal pelvis and echogenic bowel. Antenatal genetic tests for overgrowth syndromes were negative. The mother had early onset pre-eclampsia. After birth, an overgrowth syndrome was still suspected despite the baby having normal birth parameters. Raw data of the trio whole exome sequencing from the amniocentesis sample were manually inspected. Hemizygous exon 7 deletion in the GPC3 gene was found, and a postnatal diagnosis of Simpson-Golabi-Behmel syndrome, a rare overgrowth syndrome, was made. This case report discusses the significance of antenatal findings, an atypical presentation of a rare syndrome and the obstacles of diagnostic genetic testing.

A case report of multicentric carpotarsal osteolysis syndrome: Depiction of a debilitating disease course.

Multicentric carpotarsal osteolysis syndrome (MCTO) is a rare skeletal disorder characterized by progressive osteolysis involving the carpal and tarsal bones, and often associated with nephropathy. It is caused by heterozygous mutation in the MAF bZIP transcription factor B (MAFB) gene. Heterogeneous clinical manifestation and wide spectrum of disease severity have been observed in patients with MCTO. Here, we report a case of a male patient who presented with kidney failure in childhood with progressive disabling skeletal deformity. He was diagnosed with MCTO at 31-years-old, where a de novo pathogenic heterozygous variant in NM_005461.5:c.212C>A: p.(Pro71His) of the MAFB gene was identified. While there has been little data on the long-term prognosis and life expectancy of this disease, this case report sheds light on the debilitating disease course with multiple significant morbidities of a patient with MCTO throughout his lifetime of 33 years.

A review on trends in development and translation of omics signatures in cancer.

The field of cancer genomics and transcriptomics has evolved from targeted profiling to swift sequencing of individual tumor genome and transcriptome. The steady growth in genome, epigenome, and transcriptome datasets on a genome-wide scale has significantly increased our capability in capturing signatures that represent both the intrinsic and extrinsic biological features of tumors. These biological differences can help in precise molecular subtyping of cancer, predicting tumor progression, metastatic potential, and resistance to therapeutic agents. In this review, we summarized the current development of genomic, methylomic, transcriptomic, proteomic and metabolic signatures in the field of cancer research and highlighted their potentials in clinical applications to improve diagnosis, prognosis, and treatment decision in cancer patients.

Metal artifact reduction sequence-MRI abnormalities in asymptomatic patients with dual-mobility hip prostheses.

Aims: Modular dual-mobility (DM) articulations are increasingly used during total hip arthroplasty (THA). However, concerns remain regarding the metal liner modularity. This study aims to correlate metal artifact reduction sequence (MARS)-MRI abnormalities with serum metal ion levels in patients with DM articulations. Methods: A total of 45 patients (50 hips) with a modular DM articulation were included with mean follow-up of 3.7 years (SD 1.2). Enrolled patients with an asymptomatic, primary THA and DM articulation with over two years' follow-up underwent MARS-MRI. Each patient had serum cobalt, chromium, and titanium levels drawn. Patient satisfaction, Oxford Hip Score, and Forgotten Joint Score-12 (FJS-12) were collected. Each MARS-MRI was independently reviewed by fellowship-trained musculoskeletal radiologists blinded to serum ion levels. Results: Overall, two patients (4.4%) had abnormal periprosthetic fluid collections on MARS-MRI with cobalt levels > 3.0 µg/l. Four patients (8.9%) had MARS-MRI findings consistent with greater trochanteric bursitis, all with cobalt levels < 1.0 µg/l. A seventh patient had a periprosthetic fluid collection with normal ion levels. Of the 38 patients without MARS-MRI abnormalities, 37 (97.4%) had cobalt levels < 1.0 µg/l, while one (2.6%) had a cobalt level of 1.4 µg/l. One patient (2.2%) had a chromium level > 3.0 µg/l and a periprosthetic fluid collection. Of the 41 patients with titanium levels, five (12.2%) had titanium levels > 5.0 µg/l without associated MARS-MRI abnormalities. Conclusion: Periprosthetic fluid collections associated with elevated serum cobalt levels in patients with asymptomatic DM articulations occur infrequently (4.4%), but further assessment is necessary due to implant heterogeneity.

Cholangiocytes Modulate CD100 Expression in the Liver and Facilitate Pathogenic T-Helper 17 Cell Differentiation.

BACKGROUND & AIMS: Chronic inflammation surrounding bile ducts contributes to the disease pathogenesis of most cholangiopathies. Poor efficacy of immunosuppression in these conditions suggests biliary-specific pathologic principles. Here we performed biliary niche specific functional interpretation of a causal mutation (CD100 K849T) of primary sclerosing cholangitis (PSC) to understand related pathogenic mechanisms. METHODS: Biopsy specimens of explanted livers and endoscopy-guided sampling were used to assess the CD100 expression by spatial transcriptomics, immune imaging, and high-dimensional flow cytometry. To model pathogenic cholangiocyte-immune cell interaction, splenocytes from mutation-specific mice were cocultured with cholangiocytes. Pathogenic pathways were pinpointed by RNA sequencing analysis of cocultured cells and cross-validated in patient materials. RESULTS: CD100 is mainly expressed by immune cells in the liver and shows a unique pattern around PSC bile ducts with RNA-level colocalization but poor detection at the protein level. This appears to be due to CD100 cleavage as soluble CD100 is increased. Immunophenotyping suggests biliary-infiltrating T cells as the major source of soluble CD100, which is further supported by reduced surface CD100 on T cells and increased metalloproteinases in cholangiocytes after coculturing. Pathogenic T cells that adhered to cholangiocytes up-regulated genes in the T-helper 17 cell differentiation pathway, and the CD100 mutation boosted this process. Consistently, T-helper 17 cells dominate biliary-resident CD4 T cells in patients. CONCLUSIONS: CD100 exerts its functional impact through cholangiocyte-immune cell cross talk and underscores an active, proinflammatory role of cholangiocytes that can be relevant to novel treatment approaches.

Probing human heart TCA cycle metabolism and response to glucose load using hyperpolarized [2-13 C]pyruvate MRS.

INTRODUCTION: The healthy heart has remarkable metabolic flexibility that permits rapid switching between mitochondrial glucose oxidation and fatty acid oxidation to generate ATP. Loss of metabolic flexibility has been implicated in the genesis of contractile dysfunction seen in cardiomyopathy. Metabolic flexibility has been imaged in experimental models, using hyperpolarized (HP) [2-13 C]pyruvate MRI, which enables interrogation of metabolites that reflect tricarboxylic acid (TCA) cycle flux in cardiac myocytes. This study aimed to develop methods, demonstrate feasibility for [2-13 C]pyruvate MRI in the human heart for the first time, and assess cardiac metabolic flexibility. METHODS: Good manufacturing practice [2-13 C]pyruvic acid was polarized in a 5 T polarizer for 2.5-3 h. Following dissolution, quality control parameters of HP pyruvate met all safety and sterility criteria for pharmacy release, prior to administration to study subjects. Three healthy subjects each received two HP injections and MR scans, first under fasting conditions, followed by oral glucose load. A 5 cm axial slab-selective spectroscopy approach was prescribed over the left ventricle and acquired at 3 s intervals on a 3 T clinical MRI scanner. RESULTS: The study protocol, which included HP substrate injection, MR scanning, and oral glucose load, was performed safely without adverse events. Key downstream metabolites of [2-13 C]pyruvate metabolism in cardiac myocytes include the glycolytic derivative [2-13 C]lactate, TCA-associated metabolite [5-13 C]glutamate, and [1-13 C]acetylcarnitine, catalyzed by carnitine acetyltransferase (CAT). After glucose load, 13 C-labeling of lactate, glutamate, and acetylcarnitine from 13 C-pyruvate increased by an average of 39.3%, 29.5%, and 114% respectively in the three subjects, which could result from increases in lactate dehydrogenase, pyruvate dehydrogenase, and CAT enzyme activity as well as TCA cycle flux (glucose oxidation). CONCLUSIONS: HP [2-13 C]pyruvate imaging is safe and permits noninvasive assessment of TCA cycle intermediates and the acetyl buffer, acetylcarnitine, which is not possible using HP [1-13 C]pyruvate. Cardiac metabolite measurement in the fasting/fed states provides information on cardiac metabolic flexibility and the acetylcarnitine pool.

Genome-Wide DNA Methylation Profiling as Frontline Diagnostics for Central Nervous System Embryonal Tumors in Hong Kong.

This paper examines the link between CNS tumor biology and heterogeneity and the use of genome-wide DNA methylation profiling as a clinical diagnostic platform. CNS tumors are the most common solid tumors in children, and their prognosis remains poor. This study retrospectively analyzed pediatric patients with CNS embryonal tumors in Hong Kong between 1999 and 2017, using data from the territory-wide registry and available formalin-fixed paraffin-embedded tumor tissue. After processing archival tumor tissue via DNA extraction, quantification, and methylation profiling, the data were analyzed by using the web-based DKFZ classifier (Molecular Neuropathology (MNP) 2.0 v11b4) and t-SNE analysis. Methylation profiles were deemed informative in 85 samples. Epigenetic data allowed molecular subgrouping and confirmed diagnosis in 65 samples, verified histologic diagnosis in 8, and suggested an alternative diagnosis in 12. This study demonstrates the potential of DNA methylation profiling in characterizing pediatric CNS embryonal tumors in a large cohort from Hong Kong, which should enable regional and international collaboration in future pediatric neuro-oncology research.

Revealing parental mosaicism: the hidden answer to the recurrence of apparent de novo variants.

Mosaicism refers to the presence of two or more populations of genetically distinct cells within an individual, all of which originate from a single zygote. Previous literature estimated the percentage of parental mosaicism ranged from 0.33 to 25.9%. In this study, parents whose children had previously been diagnosed with developmental disorders with an apparent de novo variant were recruited. Peripheral blood, buccal and semen samples were collected from these parents if available for the detection of potential parental mosaicism using droplet digital PCR, complemented with the method of blocker displacement amplification. Among the 20 families being analyzed, we report four families with parental mosaicism (4/20, 20%). Two families have maternal gonosomal mosaicism (EYA1 and EBF3) and one family has paternal gonadal mosaicism (CHD7) with a pathogenic/ likely pathogenic variant. One family has a paternal gonosomal mosaicism with a variant of uncertain significance (FLNC) with high clinical relevance. The detectable variant allele frequency in our cohort ranged from 8.7-35.9%, limit of detection 0.08-0.16% based on our in-house EBF3 assay. Detecting parental mosaicism not only informs family with a more accurate recurrence risk, but also facilitates medical teams to create appropriate plans for pregnancy and delivery, offering the most suitable care.

Probing Human Heart TCA Cycle Metabolism and Response to Glucose Load using Hyperpolarized [2-13C]Pyruvate MR Spectroscopy.

Introduction: The normal heart has remarkable metabolic flexibility that permits rapid switching between mitochondrial glucose oxidation and fatty acid (FA) oxidation to generate ATP. Loss of metabolic flexibility has been implicated in the genesis of contractile dysfunction seen in cardiomyopathy. Metabolic flexibility has been imaged in experimental models, using hyperpolarized (HP) [2-13C]pyruvate MRI, which enables interrogation of metabolites that reflect tricarboxylic acid (TCA) cycle flux in cardiac myocytes. This study aimed to develop methods, demonstrate feasibility for [2-13C]pyruvate MRI in the human heart for the first time, and assess cardiac metabolic flexibility. Methods: Good Manufacturing Practice [2-13C]pyruvic acid was polarized in a 5T polarizer for 2.5-3 hours. Following dissolution, QC parameters of HP pyruvate met all safety and sterility criteria for pharmacy release, prior to administration to study subjects. Three healthy subjects each received two HP injections and MR scans, first under fasting conditions, followed by oral glucose load. A 5cm axial slab-selective spectroscopy approach was prescribed over the left ventricle and acquired at 3s intervals on a 3T clinical MRI scanner. Results: The study protocol which included HP substrate injection, MR scanning and oral glucose load, was performed safely without adverse events. Key downstream metabolites of [2-13C]pyruvate metabolism in cardiac myocytes include the glycolytic derivative [2-13C]lactate, TCA-associated metabolite [5-13C]glutamate, and [1-13C]acetylcarnitine, catalyzed by carnitine acetyltransferase (CAT). After glucose load, 13C-labeling of lactate, glutamate, and acetylcarnitine from 13C-pyruvate increased by 39.3%, 29.5%, and 114%, respectively in the three subjects, that could result from increases in lactate dehydrogenase (LDH), pyruvate dehydrogenase (PDH), and CAT enzyme activity as well as TCA cycle flux (glucose oxidation). Conclusions: HP [2-13C]pyruvate imaging is safe and permits non-invasive assessment of TCA cycle intermediates and the acetyl buffer, acetylcarnitine, which is not possible using HP [1-13C]pyruvate. Cardiac metabolite measurement in the fasting/fed states provides information on cardiac metabolic flexibility and the acetylcarnitine pool.

The growing needs of genetic counselling-Feasibility in utilization of tele-genetic counselling in Asia and Hong Kong.

The need for the expansion of genomic services has been at a record time high in the past decade. As technological advancement continues to strengthen the entire genetic and genomic pipeline and clinical operational workflow, the major challenge remains to be the speed of workforce development to meet service growth. In particular, the international expansion of genetic counselling (GC) services has been a topic of interest for the past few years. GC is an emerging profession in most of Asia, and in many countries the profession of GC often refers to physicians or front-line health workers with expertise in genetics to provide GC services rather than being a specific independent profession. As genetic and genomic services, especially pre-test and post-test GC, expand globally, the need to tackle the longstanding obstacles of GC personnel shortage and funding issues must not be overlooked. There is an urgent need internationally, and especially in Asia, where GC profession is comparatively less well-established, to seek alternative approaches to meet service demand. The present review examines the global development and feasibility of tele-genetics and tele-genetic counselling (TGC), and serves as the foundation to explore a possible roadmap in Hong Kong via the Hong Kong Genome Project.

Hyperpolarized [2-13C]pyruvate MR molecular imaging with whole brain coverage.

Hyperpolarized (HP) 13C Magnetic Resonance Imaging (MRI) was applied for the first time to image and quantify the uptake and metabolism of [2-13C]pyruvate in the human brain to provide new metabolic information on cerebral energy metabolism. HP [2-13C]pyruvate was injected intravenously and imaged in 5 healthy human volunteer exams with whole brain coverage in a 1-minute acquisition using a specialized spectral-spatial multi-slice echoplanar imaging (EPI) pulse sequence to acquire 13C-labeled volumetric and dynamic images of [2-13C]pyruvate and downstream metabolites [5-13C]glutamate and [2-13C]lactate. Metabolic ratios and apparent conversion rates of pyruvate-to-lactate (kPL) and pyruvate-to-glutamate (kPG) were quantified to investigate simultaneously glycolytic and oxidative metabolism in a single injection.

A randomized controlled clinical evaluation of desensitization efficacy of a newly developed toothpaste with highly stabilized SnF2.

PURPOSE: To assess the relief of dentin hypersensitivity of the new toothpaste with stabilized stannous fluoride (SnF2) versus a marketed standard fluoride toothpaste as a negative control and a marketed anhydrous SnF2 toothpaste as a positive control. METHODS: This was a single-centered, randomized, controlled, double blind, clinical trial. 96 participants with hypersensitivity were enrolled in this 4-week clinical study. Electrical stimulation and evaporative air tests were performed to evaluate the desensitization efficacy. Clinical assessments were made at baseline, and after 3 days, 1 week, 2 weeks and 4 weeks of twice-daily brushing. Additionally, the influence of Sn² ⁺ species on desensitization was evaluated using bovine dentin specimens treated with toothpaste. RESULTS: All 96 enrolled participants were randomized. 96 participants completed all evaluations. Participants had an average age (SD) of 47.0 (10.5) years; 45% of participants were female. Both SnF2 toothpastes showed superior desensitization efficacy compared to the negative control toothpaste, the conventional sodium monofluorophosphate (SMFP) toothpaste, after a week. The new stabilized SnF2 toothpaste demonstrated improved electrical stimulation benefits compared to the negative control toothpaste, with increases of 15.1% after 3 days, 34.2% after 1 week, 66.3% after 2 weeks, and 111.6% after 4 weeks. Additionally, it showed relative verbal evaluation scale (VES) benefits of 14.2% after 3 days, 37.6% after 1 week, 28.9% after 2 weeks, and 37.4% after 4 weeks. The stabilized SnF2 toothpaste exhibited desensitization properties comparable to those of a commercial anhydrous SnF2 toothpaste, which typically produces undesirable side effects in the mouth. Toothpastes containing 0.454 % SnF2 exhibited perfect occlusion of dentin tubules. CLINICAL SIGNIFICANCE: The stabilized 0.454% SnF2 toothpaste exhibited significantly greater dentin hypersensitivity relief within only a week and comparable property to commercial anhydrous SnF2 toothpaste.