Ultrasound blood flow characteristics changes in fetal umbilical artery thrombosis: A retrospective analysis.

BACKGROUND: Umbilical artery thrombosis (UAT) is extremely uncommon and leads to adverse perinatal outcomes. Hypercoagulation of blood in pregnant women is suspected to be an important risk for UAT. Ultrasound is an effective way to detect thrombosis. The mother can monitor her own fetal health using ultrasound, which enables her to take preventative action in case of emergency. AIM: To investigate ultrasonic blood signal after UAT in the umbilical artery, and evaluate the relationship between hypercoagulability and UAT. METHODS: We described a case of a newly formed UAT with markedly altered ultrasonic indices of umbilical artery blood flow, and retrospectively studied it with 18 UAT patients confirmed by histopathology from October 2019 and March 2023 in Xiamen Women and Children's Hospital. Patients' information was collected from medical archives, including maternal clinical data, neonatal outcomes, pathological findings and ultrasonic indices of umbilical artery blood flow, such as systolic-diastolic duration ratio (S/D), resistance index (RI), pulsatility index (PI) and peak systolic velocity (PSV). Ultrasound and coagulation indices were analyzed with matched samples t-test and Wilcoxon rank sum test using the statistical packages in R (version 4.2.1) including car (version 3.1-0) and stats (version 4.2.1), and visualized by ggplot2 package (version 3.3.6). RESULTS: A patient with normal findings in second and third-trimester routine ultrasound scan developed UAT with severe changes in ultrasonic indices of umbilical artery blood flow (within 2.5th of reference ranges) in a short period of time. Statistical analysis of umbilical artery blood flow ultrasound indices for 19 patients with UAT showed that the decrease in S/D, RI, and PI and increase of PSV during the disease process was greater than that of non-UAT. All 18 patients delivered in our hospital showed characteristic manifestations of UAT on histological examination after delivery, most of which (16/18) showed umbilical cord abnormalities, with 15 umbilical cord torsion and 1 pseudoknot. Coagulation parameters were not significantly changed in UAT patients compared with normal pregnancy women. CONCLUSION: Significant changes in ultrasound indicators after UAT were demonstrated. PSV can play important roles in the diagnosis of UAT. Hypercoagulability alone is not sufficient for the occurrence of UAT.

METTL3 regulates the proliferation, metastasis and EMT progression of bladder cancer through P3H4.

Bladder cancer, the most common malignant tumor in the urinary system, exhibits significantly up-regulated expression of P3H4, which is associated with pathological factors. The objective of this study was to elucidate the underlying mechanism of P3H4 in bladder cancer. Initially, we analyzed P3H4 gene expression using the TCGA database and evaluated P3H4 levels in clinical samples and various bladder cell lines. P3H4 was found to be markedly overexpressed in bladder cancer samples. Subsequently, bladder cancer cells were transfected with shRNA targeting P3H4 (sh-P3H4), sh-METTL3, and P3H4 overexpression vectors (P3H4 OE). Viability, migration, and invasion of bladder cancer cells were assessed using CCK-8, wound healing, and transwell assays. Western blot analysis was performed to determine the levels of EMT-associated proteins, while RNA stability assays determined the half-life of P3H4. Knockdown of P3H4 resulted in inhibition of bladder cancer cell proliferation, migration, invasion, and EMT progression. Mechanistically, METTL3 was found to regulate the mRNA stability of P3H4 in bladder cancer. Moreover, overexpression of P3H4 reversed the inhibitory effects of METTL3 knockdown on bladder cancer cell behaviors. Stable cell lines were established by infecting EJ cells with lentiviral vectors containing sh-METTL3 or P3H4 OE. These cells were then implanted into the skin of BALB/c nude mice, and IHC analysis was used to analyze the expression levels of EMT-associated proteins. In vivo studies demonstrated that inhibition of METTL3 suppressed bladder cancer growth and EMT through P3H4. In conclusion, our findings suggest that METTL3 regulates the proliferation, metastasis, and EMT progression of bladder cancer through P3H4, highlighting its potential as a therapeutic target.

Unveiling the Occurrence and Non-Negligible Role of Amino Sugars in Waste Activated Sludge Fermentation by an Enriched Chitin-Degradation Consortium.

Polysaccharides in extracellular polymeric substances (EPS) can form a hybrid matrix network with proteins, impeding waste-activated sludge (WAS) fermentation. Amino sugars, such as N-acetyl-d-glucosamine (GlcNAc) polymers and sialic acid, are the non-negligible components in the EPS of aerobic granules or biofilm. However, the occurrence of amino sugars in WAS and their degradation remains unclear. Thus, amino sugars (∼6.0%) in WAS were revealed, and the genera of Lactococcus and Zoogloea were identified for the first time. Chitin was used as the substrate to enrich a chitin-degrading consortium (CDC). The COD balances for methane production ranged from 83.3 and 95.1%. Chitin was gradually converted to oligosaccharides and GlcNAc after dosing with the extracellular enzyme. After doing enriched CDC in WAS, the final methane production markedly increased to 60.4 ± 0.6 mL, reflecting an increase of ∼62%. Four model substrates of amino sugars (GlcNAc and sialic acid) and polysaccharides (cellulose and dextran) could be used by CDC. Treponema (34.3%) was identified as the core bacterium via excreting chitinases (EC 3.2.1.14) and N-acetyl-glucosaminidases (EC 3.2.1.52), especially the genetic abundance of chitinases in CDC was 2.5 times higher than that of WAS. Thus, this study provides an elegant method for the utilization of amino sugar-enriched organics.

The subacute toxicity and underlying mechanisms of biomimetic mesoporous polydopamine nanoparticles.

Recently, mesoporous nanomaterials with widespread applications have attracted great interest in the field of drug delivery due to their unique structure and good physiochemical properties. As a biomimetic nanomaterial, mesoporous polydopamine (MPDA) possesses both a superior nature and good compatibility, endowing it with good clinical transformation prospects compared with other inorganic mesoporous nanocarriers. However, the subacute toxicity and underlying mechanisms of biomimetic mesoporous polydopamine nanoparticles remain uncertain. Herein, we prepared MPDAs by a soft template method and evaluated their primary physiochemical properties and metabolite toxicity, as well as potential mechanisms. The results demonstrated that MPDA injection at low (3.61 mg/kg) and medium doses (10.87 mg/kg) did not significantly change the body weight, organ index or routine blood parameters. In contrast, high-dose MPDA injection (78.57 mg/kg) is associated with disturbances in the gut microbiota, activation of inflammatory pathways through the abnormal metabolism of bile acids and unsaturated fatty acids, and potential oxidative stress injury. In sum, the MPDA dose applied should be controlled during the treatment. This study first provides a systematic evaluation of metabolite toxicity and related mechanisms for MPDA-based nanoparticles, filling the gap between their research and clinical transformation as a drug delivery nanoplatform.

Aerobic exercise mitigates hippocampal neuronal apoptosis by regulating DAPK1/CDKN2A/REDD1/FoXO1/FasL signaling pathway in D-galactose-induced aging mice.

Brain aging is the most important risk factor for neurodegenerative disorders, and abnormal apoptosis is linked to neuronal dysfunction. Specifically, studies have found that exercise effectively inhibits hippocampal neuronal apoptosis, while the molecular mechanism remains unclear. In the present study, we investigated the impact of aerobic exercise on hippocampal neuronal apoptosis in aging mice and the potential involvement of DAPK1 and its downstream pathways based on recent data that DAPK1 may be associated with neuronal death in neurodegenerative diseases. Senescent mice were subjected to 8 weeks of Aerobic training. Following behavioral testing, hippocampal samples were examined histologically and biochemically to detect pathological changes, neuronal apoptosis, and mRNA and protein levels. We found that the exercise intervention improved spatial memory and alleviated neuronal apoptosis in the brain. Notably, exercise down-regulated DAPK1 expression and inhibited Fas death receptor transactivation and the mitochondrial apoptotic pathway in the hippocampus. These results shed new light on the protective effect of regular exercise against brain aging though modulating the DAPK1 pathway.

Clinical study on cognitive impairment in Duchenne muscular dystrophy.

Our study aimed to explore the intellectual function of patients with Duchenne muscular dystrophy (DMD) in China and examine the correlation of full-scale intelligence quotient (FSIQ) with age, mutation locations, mutation class, and dystrophin isoforms. We assessed 64 boys with DMD using The Wechsler Intelligence Scales for Children-Fourth Edition and compared intellectual function at enrollment and follow-up in the 15 patients who completed the follow-up. Our findings confirm that boys with DMD may exhibit cognitive impairment, with the Working Memory Index being the most impaired. There was no significant correlation between FSIQ and age; however, a positive correlation was noted between age and the Verbal Comprehension Index. FSIQ was not associated with mutation class, the number of affected mutated exons, or mutation locations. However, there was a significant difference in FSIQ between the groups with intact and deficient Dp140. Fifteen participants adhered to glucocorticoid therapy throughout the two-year follow-up period, and eleven of them showed an improvement in FSIQ compared to their initial scores, with improvement ranging from 2 to 20. In conclusion, patients with the cumulative loss of isoforms in the brain are at a higher risk of cognitive deficits and may require early cognitive interventions.

In vivo cadmium-assisted dilute acid pretreatment of the phytoremediation sweet sorghum for enzymatic hydrolysis and cadmium enrichment.

Phytoremediation with energy crops is considered an integrated technology that provides both environment and energy benefits. Herein, the sweet sorghum cultivated on Cd-contaminated farmland (1.21 mg/kg of Cd in the soil) showed promising phytoremediation potential, and the approach for utilizing sorghum stalks was explored. Sweet sorghum bagasse with Cd contamination was pretreated with dilute acid in order to improve enzymatic saccharification and achieve Cd recovery, resulting in harmless and value-added utilization. After pretreatment, hemicelluloses were dramatically degraded, and the lignocellulosic structures were partially deconstructed with xylan removal up to 98.1%. Under the optimal condition (0.75% H2SO4), the highest total sugar yield was 0.48 g/g of raw bagasse; and nearly 98% of Cd was enriched in the liquid phase. Compared with normal biomass, Cd reduced the biomass recalcitrance and further facilitated the deconstruction of biomass under super dilute acid conditions. This work provided an example for the subsequent valorization of Cd-containing biomass and Cd recovery, which will greatly facilitate the development of phytoremediation of heavy metal contaminated soil.

Identification and degradation of structural extracellular polymeric substances in waste activated sludge via a polygalacturonate-degrading consortium.

By maintaining the cell integrity of waste activated sludge (WAS), structural extracellular polymeric substances (St-EPS) resist WAS anaerobic fermentation. This study investigates the occurrence of polygalacturonate in WAS St-EPS by combining chemical and metagenomic analyses that identify ∼22% of the bacteria, including Ferruginibacter and Zoogloea, that are associated with polygalacturonate production using the key enzyme EC 5.1.3.6. A highly active polygalacturonate-degrading consortium (GDC) was enriched and the potential of this GDC for degrading St-EPS and promoting methane production from WAS was investigated. The percentage of St-EPS degradation increased from 47.6% to 85.2% after inoculation with the GDC. Methane production was also increased by up to 2.3 times over a control group, with WAS destruction increasing from 11.5% to 28.4%. Zeta potential and rheological behavior confirmed the positive effect which GDC has on WAS fermentation. The major genus in the GDC was identified as Clostridium (17.1%). Extracellular pectate lyases (EC 4.2.2.2 and 4.2.2.9), excluding polygalacturonase (EC 3.2.1.15), were observed in the metagenome of the GDC and most likely play a core role in St-EPS hydrolysis. Dosing with GDC provides a good biological method for St-EPS degradation and thereby enhances the conversion of WAS to methane.

Dynamic structural evolution of lignin macromolecules and hemicelluloses during Chinese pine growth.

To comprehend the biosynthesis processes of conifers, it is essential to investigate the disparity between the cell wall shape and the interior chemical structures of polymers throughout the development of Chinese pine. In this study, branches of mature Chinese pine were separated according to their growth time (2, 4, 6, 8 and 10 years). The variation of cell wall morphology and lignin distribution was comprehensively monitored by scanning electron microscopy (SEM) and confocal Raman microscopy (CRM), respectively. Moreover, the chemical structures of lignin and alkali-extracted hemicelluloses were extensively characterized by nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC). The thickness of latewood cell walls increased steadily from 1.29 µm to 3.38 µm, and the structure of the cell wall components became more complicated as the growth time increased. Based on the structural analysis, it was found that the content of ß-O-4 (39.88-45.44/100 Ar), ß-ß (3.20-10.02/100 Ar) and ß-5 (8.09-15.35/100 Ar) linkages as well as the degree of polymerization of lignin increased with the growth time. The complication propensity increased significantly over 6 years before slowing to a trickle over 8 and 10 years. Furthermore, alkali-extracted hemicelluloses of Chinese pine mainly consist of galactoglucomannans and arabinoglucuronxylan, in which the relative content of galactoglucomannans increased with the growth of the pine, especially from 6 to 10 years.

Intraoperative fluoroscopy on femoral tunnel placement in the treatment of professional snow sports athletes with anterior cruciate ligament injury / 中华创伤杂志

Objective:To explore the clinical outcomes of intraoperative fluoroscopy on femoral tunnel placement in treating professional snow sports athletes with anterior cruciate ligament (ACL) injury.Methods:A retrospective case series study was used to analyze the clinical data of 13 professional snow sports athletes with ACL injury treated in the National Institute of Sports Medicine, General Administration of Sport of China from January 2016 to January 2019. There were 5 males and 8 females, aged 16-27 years [(18.5±3.0)years]. Intraoperative lateral fluoroscopy combined with quadrant method was performed for the accurate femoral tunnel placement in single-bundle ACL reconstruction by using autologous hamstring tendon in all patients. KT1000 side-to-side difference (KT1000-ssd), pivot shift test, International Knee Documentation Committee (IKDC) subjective score, Lysholm score, Marx activity scale and maximum extension and flexion resistance ratio of the involved and uninvolved knee were compared before operation (or before injury) and at 3, 6, 12 and 24 months after operation. Whether returning to the field, time taken in returning to the field and re-injury were recorded at each follow-up visit. ACL graft signal intensity ratio (SIR) in MRI of the involved knee was evaluated at postoperative 24 months.Results:All patients were followed up for 24-33 months [(25.8±2.7)months]. There were 7 patients with KT1000-ssd degree I, 5 with degree II and 1 with degree III before operation, compared to 12 patients with KT1000-ssd degree 0 and 1 with degree I at 3 and 6 months after operation and 13 patients with KT1000-ssd degree 0 at 12 and 24 months after operation. The pivot shift test was grade I in 8 patients and grade II in 5 before operation, compared to 11 patients with degree 0 and 2 with degree I at 3 months after operation and 12 patients with degree 0 and 1 with degree I at 6, 12 and 24 months after operation. IKDC subjective score was (68.0±4.3)points, (84.7±7.9)points, (94.6±3.3)points and (96.5±1.8)points at postoperative 3, 6, 12 and 24 months, respectively. Six months after operation, IKDC subjective score was significantly improved compared to the preoperative (48.3±25.0)points (all P<0.01). The Lysholm score was (63.4±6.6)points, (80.1±6.5)points, (93.8±4.6)points and (96.5±2.4)points at postoperative 3, 6, 12 and 24 months, respectively. Six months after operation, the Lysholm score was significantly improved compared to the preoperative (47.5±29.4)points (all P<0.01). The Marx activity scale was (7.4±0.5)points, (13.8±0.7)points, (14.6±0.8)points and (15.0±0.7)points at postoperative 3, 6, 12 and 24 months, respectively, significantly lower than (16.0±0.0)points before the injury (all P<0.01). The maximum extension resistance ratio of the involved and uninvolved knee was 0.60±0.10, 0.85±0.08, 0.91±0.06 and 0.97±0.04 at postoperative 3, 6, 12 and 24 months, respectively. Six months after operation, the maximum extension resistance ratio of the involved and uninvolved knee was significantly increased compared to the preoperative 0.57±0.18 (all P<0.01).The maximum flexion resistance ratios of involved and uninvolved knee were 0.64±0.09, 0.82±0.06, 0.89±0.04 and 0.94±0.06 at postoperative 3, 6, 12 and 24 months, respectively. Six months after operation, the maximum flexion resistance ratio of the involved and uninvolved knee was significantly increased compared to the preoperative 0.60±0.12 (all P<0.01). Thirteen athletes returned to the field within 12 months after operation with the time taken in returning to the field ranging from 5-12 months [(8.7±1.9)months]. There was no ACL re-injury at postoperative 24 months. The ACL graft SIR in MRI of the involved knee was 1.80±0.20 at postoperative 24 months. Conclusion:Intraoperative fluoroscopy on femoral tunnel placement in the treatment of professional snow sports athletes with ACL injury can significantly improve the knee joint stability, subjective function, sports performance and muscle strength within 6 months, and can help them return to the field within 12 months, and accelerates graft healing.

Analysis of spontaneous nystagmus and the frequency characteristics of affected semicircular canals in patients with vestibular neuritis / 中华内科杂志

Objective: To investigate the spontaneous nystagmus (SN) and the frequency characteristics of affected semicircular canals in patients with vestibular neuritis (VN). Methods: This is a cross-sectional study. A total of 61 patients with VN admitted to the Department of Neurology of Shanxi Bethune Hospital from June 2020 to October 2021, 39 were male and 22 were female, with a mean age of (46±13) years old and male to female ratio of 1.77∶1. According to SN characteristics, 61 patients were divided into non-nystagmus group(nSN), horizontal nystagmus group(hSN) and horizontal-torsional nystagmus group (htSN). Clinical data were collected, and SN, unilateral weakness (UW), directional preponderance (DP), and video head impulse test (vHIT) gain were used as observation indicators. Statistical analysis by SPSS23.0 software. Normal distributed quantitative data (age, semicircular canal gain, SN intensity) were expressed by x¯±s, non-normal distributed quantitative data (disease course, UW, DP) were expressed by M(Q1,Q3), qualitative data were expressed by rate and composition ratio, difference analysis by one-way ANOVA, rank sum test, Chi-square test or Fisher's exact probability method, considered by P value<0.05. Results: (1)The disease course of nSN, hSN and htSN was 7.0 (4.0, 12.5), 6.0 (3.5, 11.5), and 3.0 (2.0, 6.5) days respectively, and there were statistical differences (χ2=7.31,P=0.026).(2)The horizontal nystagmus intensity of htSN was (16.8±8.6)°/s, which was significantly higher than that of (9.8±4.7)°/s in hSN (t=3.71, P<0.001). There was no significant difference in the positive rate of UW between the three groups (P=0.690), and there was a significant difference in the positive rate of DP in the three groups (χ2=12.23, P=0.002). The horizontal nystagmor intensity in the htSN was positively correlated with the vertical nystagmus intensity (r=0.59, P=0.001).(3)The gain of the affected horizontal canal of the three groups was statistically different (F=8.28, P=0.001), and the gain of the horizontal canal of hSN and htSN was significantly lower than that of nSN (t=2.74, P=0.008; t=4.05, P<0.001); The gain of the affected anterior canal in the three groups was statistically different (F=5.32, P=0.008). The gain of the anterior canal in both nSN and hSN was significantly higher than that in htSN (t=3.09, P=0.003; t=2.15, P=0.036). The horizontal canal gain of htSN is positively correlated with the anterior canal gain (r=0.74, P<0.001).(4)The affected semicircular canals in the two groups with no-vertical-component nystagmus (nSN and hSN) and the htSN were counted. The composition ratio of the affected semicircular canals in the two groups was different (χ2=8.34, P=0.015). Conclusion: The occurrence of SN in patients with VN is related to many factors, such as the disease course, low and high frequencies, and the severity of the condition in the affected semicircular canal.

Unveiling the Migration and Transformation Mechanism of Lignin in Eucalyptus During Deep Eutectic Solvent Pretreatment.

Deep eutectic solvents (DESs) have unique advantages in biomass conversion. However, the migration and transformation mechanism of lignin in the cell wall during the DES pretreatment is still elusive. In this work, Eucalyptus blocks were pretreated in choline chloride/lactic acid DES to reveal the lignin migration. Meanwhile, the remaining lignin in the pretreated residue, the regenerated DES lignin, and the solubilized degraded lignin in the recovered DES were investigated to decipher the lignin transformation. Results showed that the DES pretreatment resulted in the penetration of DES from the cell lumen to the cell wall, and lignin in the secondary wall was more easily dissolved than that in the cell corner middle lamella. The syringyl unit of lignin was better stabilized in the DES than the guaiacyl unit of lignin. The condensed lignin fraction mainly remained in the pretreated residue, while the solubilized degraded lignin fraction was monomeric aromatic ketone compounds. This study elucidates the fate of lignin during the DES pretreatment, which could also promote the development of a modern lignocellulosic pretreatment technique.

Ultrastructural elucidation of lignin macromolecule from different growth stages of Chinese pine.

Understanding of the morphological changes at different growth stages and lignin accumulation pattern for pine biomass plays the key role in facilitating the further development of value-added utilization and downstream conversion processes. This work systematically revealed the morphological change and lignin accumulation pattern in Chinese pine branches cell walls via confocal Raman microscopy (CRM) technology. Meanwhile, the structural characteristics of isolated lignin samples from different growth stages were synthetically characterized by nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC) techniques. The results indicated that the content of pith in adult pine new branch was bigger than juvenile trees. With the increase of physiological age, the branches in adult pine could accumulate more lignin both in overall content and the concentration of cell corner middle layer. Moreover, the significantly increases of molecular weights and the ß-O-4, ß-ß linkages content revealed that the lignin macromolecule of pine would polymerize faster in the adult stage (14, 35 years). The panorama generated from the structural and chemical features of pine native lignin not only benefited to understand the biosynthetic pathways and lignin macromolecules structural variation in plant cell walls from different growth stages but also contributed to the valorization and deconstruction of biomass.

Eculizumab in low-middle income countries: how much does a life cost?

Atypical hemolytic uremic syndrome (aHUS) is an ultra-rare disease and eculizumab was approved as first line therapy in 2011 by the Food and Drug Administration. Access to eculizumab in low-middle income countries is challenging. We discuss access to eculizumab in Brazil that was made possible by judicialization or compassionate use. We showed a nationwide cohort of unplanned eculizumab interruptions resulted in higher rates of aHUS relapse. Similar to the French cohort, the use of eculizumab after transplantation showed superior graft survival compared to conventional treatment. We speculate a possible solution to the higher cost of eculizumab in which the government negotiates with the manufacturers. In this process, the government should compromise to ensure validated protocols of drug use, and the pharmaceutical companies, on the other hand, should reduce prices, especially in low-income countries. We also suggest a price adjustment based on gross domestic product.

Caproate production from xylose via the fatty acid biosynthesis pathway by genus Caproiciproducens dominated mixed culture fermentation.

Caproate production from organic wastes is deemed as a novel strategy in mixed culture fermtation (MCF). However, producing caproate from natural sugar of xylose by MCF is seldom reported and the metabolic pathway is still unclear. Thus, the caproate production from xylose was investigated in this study by mesophilic MCF. The results showed that the caproate concentration from xylose (10 g/L) was 1.2 ± 0.17 g/L (equal to 2.7 gCOD/L) under pH 5.0. Dosing extra ethanol of 5 g/L could slightly increase the caproate production by âˆ¼ 30% (i.e., 1.6 g/L). While dosing extra acetate of 5 g/L negatively affected the caproate production, which was just 0.2 g/L. The microbial analysis illustrated that genus Caproiciproducens was a main identified caproate producer, occupying over 80% of enriched mixed culture. The fatty acid biosynthesis pathway was identified via metagenomic analysis. These unexpected differences extended the understanding of caproate production from organic wastes.

Natural history of spinal muscular atrophy in children: an analysis of 117 cases. / 117ä¾‹å„¿ç«¥è„Šé«“æ€§è‚ŒèŽç¼©ç—‡è‡ªç„¶ç— å²åˆ†æž.

OBJECTIVES: To study the natural history of spinal muscular atrophy (SMA) in Chongqing and surrounding areas, China, and to provide a clinical basis for comprehensive management and gene modification therapy for SMA. METHODS: A retrospective analysis was performed on the medical data and survival status of 117 children with SMA. RESULTS: Of the 117 children, 62 (53.0%) had type 1 SMA, 45 (38.5%) had type 2 SMA, and 10 (8.5%) had type 3 SMA, with a median age of onset of 2 months, 10 months, and 15 months, respectively. Compared with the children with type 2 SMA or type 3 SMA, the children with type 1 SMA had significantly shorter time to onset, consultation, and confirmed diagnosis (P<0.05) and a significantly shorter diagnostic time window (age from disease onset to consultation) (P<0.05). Pneumonia as the initial symptom, weakness in head control, crying weakness, and eating difficulty were more commonly observed in children with type 1 SMA (P<0.05). Scoliosis and lower limb joint contracture were more common in children with type 2 SMA than in those with type 1 SMA (P<0.05). All 117 SMA children (100%) had homozygous deletion of the SMN1 gene, and the homozygous deletion of exon 7 was the most common type (68.4%, 80/117). The 6-year survival rate of children with type 1 SMA was only 10%±5%, which was significantly lower than that of children with type 2 or 3 SMA (P<0.05). Age of onset ≤3 months, pneumonia as the initial symptom and weakness in head control were the risk factors for death in children with type 1 SMA (P<0.05). The children with type 2 SMA had non-linear regression of motor ability. CONCLUSIONS: There are differences in clinical manifestations and survival rates among children with different types of SMA. The children with type 1 SMA have a low survival rate, and those with type 2 SMA may have non-linear regression of motor ability. Early identification and management of SMA should be performed in clinical practice.

Thrombotic microangiopathy after kidney transplantation: Analysis of the Brazilian Atypical Hemolytic Uremic Syndrome cohort.

BACKGROUND: Atypical Hemolytic Uremic Syndrome (aHUS) is an ultra-rare disease that potentially leads to kidney graft failure due to ongoing Thrombotic Microangiopathy (TMA). The aim was evaluating the frequency of TMA after kidney transplantation in patients with aHUS in a Brazilian cohort stratified by the use of the specific complement-inhibitor eculizumab. METHODS: This was a multicenter retrospective cohort study including kidney transplant patients diagnosed with aHUS. We collected data from 118 transplant centers in Brazil concerning aHUS transplanted patients between 01/01/2007 and 12/31/2019. Patients were stratified into three groups: no use of eculizumab (No Eculizumab Group), use of eculizumab for treatment of after transplantation TMA (Therapeutic Group), and use of eculizumab for prophylaxis of aHUS recurrence (Prophylactic Group). RESULTS: Thirty-eight patients with aHUS who received kidney transplantation were enrolled in the study. Patients' mean age was 30 years (24-40), and the majority of participants was women (63% of cases). In the No Eculizumab Group (n = 11), there was a 91% graft loss due to the TMA. The hazard ratio of TMA graft loss was 0.07 [0.01-0.55], p = 0.012 in the eculizumab Prophylactic Group and 0.04 [0.00-0.28], p = 0.002 in the eculizumab Therapeutic Group. CONCLUSION: The TMA graft loss in the absence of a specific complement-inhibitor was higher among the Brazilian cohort of kidney transplant patients. This finding reinforces the need of eculizumab use for treatment of aHUS kidney transplant patients. Cost optimization analysis and the early access to C5 inhibitors are suggested, especially in low-medium income countries.

The Genotype and Phenotype of Proline-Rich Transmembrane Protein 2 Associated Disorders in Chinese Children.

Objectives: To study the genetic and clinical characteristics of Chinese children with pathogenic proline-rich transmembrane protein 2 (PRRT2) gene-associated disorders. Methods: Targeted next generation sequencing (NGS) was used to identify pathogenic PRRT2 variations in Chinese children with epilepsy and/or kinesigenic dyskinesia. Patients with confirmed PRRT2-associated disorders were monitored and their clinical data were analyzed. Results: Forty-four patients with pathogenic PRRT2 variants were recruited. Thirty-five of them (79.5%) had heterozygous mutations, including 30 frameshifts, three missenses, one nonsense, and one splice site variant. The c.649dupC was the most common variant (56.8%). Eight patients (18.2%) showed whole gene deletions, and one patient (2.3%) had 16p11.2 microdeletion. Thirty-four cases (97.1%) were inherited and one case (2.9%) was de novo. Forty patients were diagnosed with benign familial infantile epilepsy (BFIE), two patients had paroxysmal kinesigenic dyskinesia (PKD) and two had infantile convulsions and choreoathetosis (ICCA). Patients with whole gene deletions had a later remission than patients with heterozygous mutations (13.9 vs. 7.1 months, P = 0.001). Forty-two patients were treated with antiseizure medications (ASMs). At last follow-up, 35 patients, including one who did not receive therapy, were asymptomatic, and one patient without ASMs died of status epilepticus at 12 months of age. One patient developed autism, and one patient showed mild developmental delay/intellectual disability. Conclusion: Our data suggested that patients with whole gene deletions could have more severe manifestations in PRRT2-associated disorders. Conventional ASMs, especially Oxcarbazepine, showed a good treatment response.

A machine learning prediction model for waiting time to kidney transplant.

BACKGROUND: Predicting waiting time for a deceased donor kidney transplant can help patients and clinicians to discuss management and contribute to a more efficient use of resources. This study aimed at developing a predictor model to estimate time on a kidney transplant waiting list using a machine learning approach. METHODS: A retrospective cohort study including data of patients registered, between January 1, 2000 and December 31, 2017, in the waiting list of São Paulo State Organ Allocation System (SP-OAS) /Brazil. Data were randomly divided into two groups: 75% for training and 25% for testing. A Cox regression model was fitted with deceased donor transplant as the outcome. Sensitivity analyses were performed using different Cox models. Cox hazard ratios were used to develop the risk-prediction equations. RESULTS: Of 54,055 records retrieved, 48,153 registries were included in the final analysis. During the study period, approximately 1/3 of the patients were transplanted with a deceased donor. The major characteristics associated with changes in the likelihood of transplantation were age, subregion, cPRA, and frequency of HLA-DR, -B and -A. The model developed was able to predict waiting time with good agreement in internal validation (c-index = 0.70). CONCLUSION: The kidney transplant waiting time calculator developed shows good predictive performance and provides information that may be valuable in assisting candidates and their providers. Moreover, it can significantly improve the use of economic resources and the management of patient care before transplant.

Exploring the causes of the high incidence of delayed graft function after kidney transplantation in Brazil: a multicenter study.

This retrospective multicenter (n = 18) cohort study evaluated the incidence, risk factors, and the impact of delayed graft function (DGF) on 1-year kidney transplant (KT) outcomes. Of 3992 deceased donor KT performed in 2014-2015, the incidence of DGF was 54%, ranging from 29.9% to 87.7% among centers. Risk factors (lower-bound-95%CI OR upper-bound-95%CI ) were male gender (1.066 1.2491.463 ), diabetic kidney disease (1.053 1.2961.595 ), time on dialysis (1.005 1.0071.009 ), retransplantation (1.035 1.3971.885 ), preformed anti-HLA antibodies (1.011 1.3831.892 ), HLA mismatches (1.006 1.0661.130 ), donor age (1.011 1.0171.023 ), donor final serum creatinine (sCr) (1.239 1.3171.399 ), cold ischemia time (CIT) (1.031 1.0431.056 ), machine perfusion (0.401 0.5420.733 ), and induction therapy with rabbit antithymocyte globulin (rATG) (0.658 0.8000.973 ). Duration of DGF > 4 days was associated with inferior renal function and DGF > 14 days with the higher incidences of acute rejection, graft loss, and death. In conclusion, the incidence and duration of DGF were high and associated with inferior graft outcomes. While late referral and poor donor maintenance account for the high overall incidence of DGF, variability in donor and recipient selection, organ preservation method, and type of induction agent may account for the wide variation observed among transplant centers.