Genotypic and Phenotypic Spectrum of maple syrup urine disease in Zhejiang of China.

BACKGROUND: Maple Syrup Urine Disease (MSUD) is an autosomal recessive metabolic disorder originating from defects in the branched-chain α-ketoacid dehydrogenase (BCKDH) complex encoded by BCKDHA, BCKDHB, and DBT. This condition presents a spectrum of symptoms and potentially fatal outcomes. Although numerous mutations in the BCKDH complex genes associated with MSUD have been identified, the relationship between specific genotypes remains to be fully elucidated. AIM: Our objective was to predict the pathogenicity of these genetic mutations and establish potential links between genotypic alterations and the clinical phenotypes of MSUD. DESIGN: Retrospective population-based cohort. METHODS: We analyzed 20 MSUD patients from the Children's Hospital at Zhejiang University School of Medicine (Hangzhou, China), recorded from January 2010 to May 2023. Patients' blood samples were collected by heel-stick through neonatal screening, and amino acid profiles were measured by tandem mass spectrometry. In silico methods were employed to assess the pathogenicity, stability, and biophysical properties. Various computation tools were utilized for assessment, namely PredictSNP, MAGPIE, iStable, Align GVGD, ConSurf and SNP effect. RESULTS: We detected 25 distinct mutations, including 12 novel mutations. The BCKDHB gene was the most commonly affected (53.3%) compared to the BCKDHA gene (20.0%) and DBT gene (26.7%). In silico webservers predicted all novel mutations were disease-causing. CONCLUSIONS: This study highlights the genetic complexity of MSUD and underscores the importance of early detection and intervention. Integrating neonatal screening with advanced sequencing methodologies is pivotal in ensuring precise diagnosis and effective management of MSUD, thereby significantly improving the prognosis for individuals afflicted with this condition.

Lipidomic profiles in serum and urine in children with steroid sensitive nephrotic syndrome.

BACKGROUND: Steroid-sensitive nephrotic syndrome (SSNS) accounts for approximately 80% of cases of nephrotic syndrome. The involvement of aberrant lipid metabolism in early SSNS is poorly understood, warranting further investigation. This study aimed to explore alterations in lipid metabolism associated with SSNS pathogenesis. METHODS: A screening cohort containing serum (50 SSNS, 37 controls) and urine samples (27 SSNS, 26 controls) was analyzed by untargeted lipidomic profiling using UHPLC-QTOF-MS. Then, a validation cohort (20 SSNS, 56 controls) underwent further analysis to check the potential clinical application by ROC curve analysis. RESULTS: Lipidomic profiling of serum and urine samples revealed significant lipid alterations in SSNS patients, with the alterations in the serum samples being more significant. An elevated concentration of PE and PG and downregulated concentration of FA were observed in SSNS serum. A total of 38 dysregulated lipids and 5 lipid metabolic pathways were identified in the serum samples in SSNS patients. Validation in the second cohort confirmed differential regulation of nine kinds of lipids, including 5 up-regulated substances [SM d33:2 (m/z = 686.5361), SHexCer d34:1 (m/z = 779.521), PI 20:4_22:4 (m/z = 934.5558), Cer_NS d18:1_23:0 (m/z = 635.6216), and GM3 d36:1 (m/z = 1180.7431)], as well as 4 down-regulated substances: [CE 18:1 (m/z = 650.601), PE 38:6 (m/z = 763.5205), PC 17:0_20:4 (m/z = 795.5868) and EtherPC 16:2e_20:4 (m/z = 763.5498)]. CONCLUSIONS: Untargeted lipidomic analysis successfully identified specific lipid class changes in patients with SSNS, providing a deeper understanding of lipid alterations and underlying mechanisms associated with SSNS.

Increased Body Mass Index is Associated with Worse Mid- To Long-Term Patient Outcomes after Surgical Repair of Multiligamentous Knee Injuries.

We evaluated the relationship between elevated body mass index (BMI) and mid- to long-term outcomes after surgical treatment of multiligamentous knee injury (MLKI). Records identified patients treated surgically for MLKI at a single institution. Inclusion criteria: minimum 2 years since surgery, complete demographics, surgical data, sustained injuries to two or more ligaments in one or both knees, and available for follow-up. Patients were contacted to complete patient-reported outcomes assessments and were classified according to mechanism of injury. Multivariate logistic regression analysis was used to predict the impact of BMI on outcome scores. A total of 77 patients (72.7% male) were included with a mean age at the time of injury of 29.4 ± 11.0 years and a mean BMI of 30.5 ± 9.4 kg/m2. The mean length of follow-up was 7.4 years. For each 10 kg/m2 increase in BMI, there is a 0.9-point decrease in Tegner activity scale (p = 0.001), a 5-point decrease in Knee Injury and Osteoarthritis Outcome Score (KOOS)-pain (p = 0.007), a 5-point decrease in KOOS-ADL (p = 0.003), a 10-point decrease in KOOS-QOL (p = 0.002), and an 11-point decrease in KOOS-Sport (p = 0.002). There were no significant correlations with BMI and Pain Catastrophizing Scale or Patient Health Questionnaire scores. Increasing BMI has a negative linear relationship with mid- to long-term clinical outcomes including pain, ability to perform activities of daily living, quality of life, and ability to perform more demanding physical activity after MLKI. BMI does not appear to have a significant relationship with knee swelling and mechanical symptoms or patients' mental health.

A Review of Inactivated COVID-19 Vaccine Development in China: Focusing on Safety and Efficacy in Special Populations.

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been widespread globally, and vaccination is critical for preventing further spread or resurgence of the outbreak. Inactivated vaccines made from whole inactivated SARS-CoV-2 virus particles generated in Vero cells are currently the most widely used COVID-19 vaccines, with China being the largest producer of inactivated vaccines. As a result, the focus of this review is on inactivated vaccines, with a multidimensional analysis of the development process, platforms, safety, and efficacy in special populations. Overall, inactivated vaccines are a safe option, and we hope that the review will serve as a foundation for further development of COVID-19 vaccines, thus strengthening the defense against the pandemic caused by SARS-CoV-2.

Accuracy of a digital workflow for bimaxillary orthognathic surgery: comparison of planned and actual outcomes.

AIM: The aim of the present prospective proof-of-concept study was to evaluate the accuracy of 3D orthognathic surgical planning and CAD/CAM splints by comparing planned with actual postoperative outcomes. MATERIALS AND METHODS: Ten patients scheduled for bimaxillary orthognathic surgery to correct a skeletal Class III dentofacial deformity were recruited. All subjects had CBCT scans taken not more than 2 months preoperatively and within the 1-week postoperative period. The distance between six dental landmarks (midpoint of the maxillary and mandibular incisors, mesiobuccal cusps of the maxillary and mandibular first molars) and three intersecting symmetry planes (Frankfort horizontal plane [FHP], midsagittal plane [MSP], and coronal plane [CP]) were measured, and the differences between the virtually simulated and actual postoperative models were computed. The threshold for accuracy was set at 2 mm. RESULTS: Differences between the planned and actual outcomes were analyzed via chi-square tests and two-tailed paired student t tests. The overall mean linear difference for all six landmarks was 0.98 mm. The overall mean linear differences for both maxillary and mandibular landmarks relative to the FHP, MSP, and CP were 1.3, 0.7, and 0.9 mm, respectively. Four cases showed all linear differences of the six landmarks to be < 2.0 mm, while the other six cases had at least one linear difference of > 2.0 mm, the majority of which were in the superior-inferior direction. There were statistically significantly greater inaccuracies in the FHP compared with the MSP and CP (P < 0.05). CONCLUSION: Most of the linear differences between the simulated and actual outcomes were clinically acceptable. However, greater linear differences were seen in the superior-inferior direction, indicating a greater surgical error in achieving the desired vertical position of the maxillomandibular complex. (Int J Comput Dent 2022;25(4):397-0; doi: 10.3290/j.ijcd.b2599749).

Canine and Premolar Root Dimensions in Chinese. A Reference for Osteoodontokeratoprosthesis Surgery.

PURPOSE: Osteoodontokeratoprosthesis (OOKP) surgery is used to restore vision in end-stage corneal disorders, where an autogenous tooth supporting an optical cylinder is implanted through the cornea under a buccal mucosal graft. The ideal tooth for OOKP is a healthy single-rooted permanent tooth with sufficient buccolingual/palatal root diameter to accommodate an optical cylinder. The aim of this study was to determine the buccolingual/palatal diameters of canine and premolar roots in Chinese, for selection of teeth for OOKP surgery. DESIGN: This was an anatomical study on root dimensions of extracted intact teeth. METHODS: Extracted canine and premolar teeth (excluding maxillary first premolars) were collected and the buccolingual/palatal and mesiodistal diameters of the root at the cervical line and at 2-mm intervals below the cervical line were measured with Vernier calipers. Other measurements included total tooth length, crown buccolingual/palatal diameter, and root length. Mean and minimum buccolingual/palatal root diameters were compiled for each 2-mm interval. RESULTS: A total of 415 extracted teeth (198 male, 217 female) were collected and measured. Recorded dimensions of keratoprostheses in 55 previous OOKP surgeries were used to establish acceptable lamina dimensions to ascertain root size adequacy. Premolars in Chinese female patients were undersized in a small minority. Minimal dimensions of teeth were insufficient if at 6 mm root level, the buccolingual/palatal width was less than 5 mm, or the mesiodistal width was less than 3 mm. This was noted in female mandibular first premolars (5.6%), maxillary second premolars (4.5%), and mandibular second premolars (1.5%). CONCLUSIONS: Canines have adequate dimensions for OOKP surgery. However, premolars in Chinese females may be undersized in a small minority.

Novel 3D polycaprolactone scaffold for ridge preservation--a pilot randomised controlled clinical trial.

OBJECTIVES: This pilot randomised controlled clinical trial aimed to evaluate the feasibility and effectiveness of using a polycaprolactone (PCL) scaffold in fresh extraction sockets for ridge preservation. The hypothesis was that the insertion of a 3D bioresorbable PCL scaffold in fresh extraction sockets allowed for normal bone healing and better maintenance of ridge dimensions after 6 months as compared to extraction sockets without the scaffold. MATERIAL AND METHODS: Thirteen patients were randomised to either the test group (N = 6) where a PCL scaffold was inserted in the tooth socket after extraction or the control group (N = 7) where no space filler was used. Alveolar ridge height and width measurements were made at baseline and 6 months post-extraction, for the evaluation of bone resorption. At 6 months, a core of bone was trephined out from the healed ridge for microcomputed tomographic (micro CT) and histological analyses, immediately before Stage I dental implant surgery. Stage II dental implant surgery was performed 4-6 months later. RESULTS: There was less vertical ridge resorption in the test group compared to the control group, and the difference was statistically significant in the mesio-buccal aspect (P = 0.008). Micro CT and histological observations showed mainly mineralised bone formation in both groups, except for one specimen in the test group. CONCLUSIONS: The insertion of a 3D bioresorbable PCL scaffold in fresh extraction sockets allowed for normal bone healing, and there was better maintenance of ridge height after 6 months as compared to extraction sockets without the scaffold.