Compositional Control of Phase-Separated Cellular Bodies.

Cellular bodies such as P bodies and PML nuclear bodies (PML NBs) appear to be phase-separated liquids organized by multivalent interactions among proteins and RNA molecules. Although many components of various cellular bodies are known, general principles that define body composition are lacking. We modeled cellular bodies using several engineered multivalent proteins and RNA. In vitro and in cells, these scaffold molecules form phase-separated liquids that concentrate low valency client proteins. Clients partition differently depending on the ratio of scaffolds, with a sharp switch across the phase diagram diagonal. Composition can switch rapidly through changes in scaffold concentration or valency. Natural PML NBs and P bodies show analogous partitioning behavior, suggesting how their compositions could be controlled by levels of PML SUMOylation or cellular mRNA concentration, respectively. The data suggest a conceptual framework for considering the composition and control thereof of cellular bodies assembled through heterotypic multivalent interactions.

Transcription factors interact with RNA to regulate genes.

Transcription factors (TFs) orchestrate the gene expression programs that define each cell's identity. The canonical TF accomplishes this with two domains, one that binds specific DNA sequences and the other that binds protein coactivators or corepressors. We find that at least half of TFs also bind RNA, doing so through a previously unrecognized domain with sequence and functional features analogous to the arginine-rich motif of the HIV transcriptional activator Tat. RNA binding contributes to TF function by promoting the dynamic association between DNA, RNA, and TF on chromatin. TF-RNA interactions are a conserved feature important for vertebrate development and disrupted in disease. We propose that the ability to bind DNA, RNA, and protein is a general property of many TFs and is fundamental to their gene regulatory function.

Biomolecular condensates: organizers of cellular biochemistry.

Biomolecular condensates are micron-scale compartments in eukaryotic cells that lack surrounding membranes but function to concentrate proteins and nucleic acids. These condensates are involved in diverse processes, including RNA metabolism, ribosome biogenesis, the DNA damage response and signal transduction. Recent studies have shown that liquid-liquid phase separation driven by multivalent macromolecular interactions is an important organizing principle for biomolecular condensates. With this physical framework, it is now possible to explain how the assembly, composition, physical properties and biochemical and cellular functions of these important structures are regulated.

Role of condensates in modulating DNA repair pathways and its implication for chemoresistance.

For cells, it is important to repair DNA damage, such as double-strand and single-strand DNA breaks, because unrepaired DNA can compromise genetic integrity, potentially leading to cell death or cancer. Cells have multiple DNA damage repair pathways that have been the subject of detailed genetic, biochemical, and structural studies. Recently, the scientific community has started to gain evidence that the repair of DNA double-strand breaks may occur within biomolecular condensates and that condensates may also contribute to DNA damage through concentrating genotoxic agents used to treat various cancers. Here, we summarize key features of biomolecular condensates and note where they have been implicated in the repair of DNA double-strand breaks. We also describe evidence suggesting that condensates may be involved in the repair of other types of DNA damage, including single-strand DNA breaks, nucleotide modifications (e.g., mismatch and oxidized bases), and bulky lesions, among others. Finally, we discuss old and new mysteries that could now be addressed considering the properties of condensates, including chemoresistance mechanisms.

Exercise recommendations for patients with myositis: a narrative review of safety and efficacy.

Idiopathic inflammatory myopathies (IIM) are marked by progressive muscle weakness and lasting disability. Therapies targeting patient well-being include the use of prescription drugs as well as exercise. Maintaining or increasing muscular strength and endurance as well as cardiorespiratory fitness (CRF) improves quality of life (QoL) as well as functional status in IIM patients. This narrative review highlights exercise interventions in patients of different IIM subtypes with the intent to provide a summary table with exercise recommendations that will safely and effectively improve QoL in myositis patients.

Diagnosis and management of metabolic myopathies.

Metabolic myopathies are a set of rare inborn errors of metabolism leading to disruption in energy production. Relevant to skeletal muscle, glycogen storage disease and fatty acid oxidation defects can lead to exercise intolerance, rhabdomyolysis, and weakness in children and adults, distinct from the severe forms that involve multiple-organ systems. These nonspecific, dynamic symptoms along with conditions that mimic metabolic myopathies can make diagnosis challenging. Clinicians can shorten the time to diagnosis by recognizing the typical clinical phenotypes and performing next generation sequencing. With improved access and affordability of molecular testing, clinicians need to be well-versed in resolving variants of uncertain significance relevant to metabolic myopathies. Once identified, patients can improve quality of life, safely engage in exercise, and reduce episodes of rhabdomyolysis by modifying diet and lifestyle habits.

Minimizing total weighted latency in home healthcare routing and scheduling with patient prioritization.

We study a home healthcare routing and scheduling problem, where multiple healthcare service provider teams should visit a given set of patients at their homes. The problem involves assigning each patient to a team and generating the routes of the teams such that each patient is visited once. When patients are prioritized according to the severity of their condition or their service urgency, the problem minimizes the total weighted waiting time of the patients, where the weights represent the triage levels. In this form, the problem generalizes the multiple traveling repairman problem. To obtain optimal solutions for small to moderate-size instances, we propose a level-based integer programming (IP) model on a transformed input network. To solve larger instances, we develop a metaheuristic algorithm that relies on a customized saving procedure and a general variable neighborhood search algorithm. We evaluate the IP model and the metaheuristic on various small-, medium- and large-sized instances coming from the vehicle routing literature. While the IP model finds the optimal solutions to all the small- and medium-sized instances within three hours of run time, the metaheuristic algorithm achieves the optimal solutions to all instances within merely a few seconds. We also provide a case study involving Covid-19 patients in a district of Istanbul and derive insights for the planners by means of several analyses.

Racial disparities in skin tone representation of dermatomyositis rashes: a systematic review.

OBJECTIVE: This systemic review assesses skin tone representation in images of DM rashes in medical education literature. METHODS: A review was performed of 59 dermatology, 11 neurology, 10 neuromuscular, 7 rheumatology and 6 internal medicine textbooks published between 2011 and 2021 and 3 online image databases (UpToDate, VisualDx and DermNet NZ) that were available through an online medical school library. After extracting images, images with poor lighting or unclear rashes were removed. Authors graded skin tone independently on the Massey and Martin Skin Colour Scale (MMSCS) from 1 (very light) to 10 (very dark). The median score was taken for a final score, grouped within MMSCS 1-2, 3-4, 5-7 or 8-10. Inter-rater reliability was assessed using Kendall's coefficient of concordance (W). RESULTS: Six hundred and twenty-one images were extracted after reviewing 93 textbooks and 3 online databases. Of the 561 images analysed, 73.1% of images represented MMSCS 1-2, followed by 3-4 (13.4%), 5-7 (11.8%) and 8-10 (1.8%). Inter-rater reliability was high (W = 0.835). Of the images in MMSCS 5-10, 59.2% were in online databases and 80.6% of textbook images were in dermatology books. CONCLUSIONS: Patients with lighter skin tones were represented in a higher number of DM-related educational materials compared with patients with darker skin tones. Our findings add to current research implicating that darker skin tones are under-represented in cutaneous educational materials, specifically for DM. This leads to the inability to properly characterize skin involvement in DM and may lead to inappropriate exclusion from clinical trials due to erroneous skin scoring.

A secondary analysis of PAIN-CONTRoLS: Pain's impact on sleep, fatigue, and activities of daily living.

INTRODUCTION/AIMS: Peripheral neuropathies commonly affect quality of life of patients due to pain, sleep disturbances, and fatigue, although trials have not adequately explored these domains of care. The aim of this study was to assess the impact of nortriptyline, duloxetine, pregabalin, and mexiletine on pain, sleep, and fatigue in patients diagnosed with cryptogenic sensory polyneuropathy (CSPN). METHODS: We implemented a Bayesian adaptive design to perform a 12-wk multisite, randomized, prospective, open-label comparative effectiveness study in 402 CSPN patients. Participants received either nortriptyline (n = 134), duloxetine (n = 126), pregabalin (n = 73), or mexiletine (n = 69). At prespecified analysis timepoints, secondary outcomes, Patient Reported Outcomes Measurement Information System (PROMIS) surveys including Short Form (SF)-12, pain interference, fatigue, and sleep disturbance, were collected. RESULTS: Mexiletine had the highest quit rate (58%) due to gastrointestinal side effects, while nortriptyline (38%) and duloxetine (38%) had the lowest quit rates. If tolerated for the full 12 wk of the study, mexiletine had the highest probability (>90%) of positive outcomes for improvements in pain interference and fatigue. There was no significant difference among the medications for sleep disturbance or SF-12 scores. Adverse events and lack of efficacy were the two most common reasons for cessation of therapy. DISCUSSION: Physicians caring for patients with CSPN should consider mexiletine to address pain and fatigue, although nortriptyline and duloxetine are better medications to trial first since they are better tolerated. Future research should compare other commonly used medications for CSPN to determine evidence-based treatment strategies.

Splice-disrupt genomic variants in prostate cancer.

BACKGROUND: Splice-disrupt genomic variants are one of the causes of cancer-causing errors in gene expression. Little is known about splice-disrupt genomic variants. METHODS AND RESULTS: Here, pattern of splice-disrupt variants was investigated using 21,842,764 genomic variants in different types of prostate cancer. A particular attention was paid to genomic locations of splice-disrupt variants on target genes. HLA-A in prostate cancer, MSR1 in familial prostate cancer, and EGFR in both castration-resistant prostate cancer and metastatic castration-resistant had the highest allele frequencies of splice-disrupt variations. Some splice-disrupt variants, located on coding sequences of NCOR2, PTPRC, and CRP, were solely present in the advanced metastatic castration-resistant prostate cancer. High-risk splice-disrupt variants were identified based on computationally calculated Polymorphism Phenotyping (PolyPhen), Sorting Intolerant From Tolerant (SIFT), and Genomic Evolutionary Rate Profiling (GERP) + + scores as well as the recorded clinical significance in dbSNP database of NCBI. Functional annotation of damaging splice-disrupt variants highlighted important cancer-associated functions, including endocrine resistance, lipid metabolic process, steroid metabolic process, regulation of mitotic cell cycle, and regulation of metabolic process. This is the first study that profiles the splice-disrupt genomic variants and their target genes in prostate cancer. Literature mining based variant analysis highlighted the importance of rs1800716 variant, located on the CYP2D6 gene, involved in a range of important functions, such as RNA spicing, drug interaction, death, and urotoxicity. CONCLUSIONS: This is the first study that profiles the splice-disrupt genomic variants and their target genes in different types of prostate cancer. Unravelling alternative splicing opens a new avenue towards the establishment of new diagnostic and prognostic markers for prostate cancer progression and metastasis.

Identifying the alpha-glucosidase inhibitory potential of dietary phytochemicals against diabetes mellitus type 2 via molecular interactions and dynamics simulation.

The research aims to identify the inhibitory potential of natural dietary phytochemicals against non-insulinotropic target protein alpha-glucosidase and its possible implications to diabetes mellitus type 2. A data set of sixteen plant-derived dietary molecules viz., 4,5-dimethyl-3-hydroxy-2(5H)-furanone, apigenin, bromelain, caffeic acid, cholecalciferol, dihydrokaempferol 7-o-glucopyranoside, galactomannan, genkwanin, isoimperatorin, luteolin, luteolin 7-o-glucoside, neohesperidin, oleanoic acid, pelargonidin-3-rutinoside, quercetin, and quinic acid were taken to accomplish molecular docking succeeded by their comparison with known inhibitors including acarbose, miglitol, voglibose, emiglitate, and 1-deoxynojirimycin. Among all phyto-compounds, bromelain (ΔG: -9.54 kcal/mol), cholecalciferol (-8.47 kcal/mol), luteolin (-9.02 kcal/mol), and neohesperidin (-8.53 kcal/mol) demonstrated better binding interactions with alpha-glucosidase in comparison to the best-known inhibitor, acarbose (ΔG: -7.93 kcal/mol). Molecular dynamics simulation of 10 ns duration, CYP450 site of metabolism identification, and prediction of activity spectra for substances depicted the bromelain as the most stable inhibitor compared to luteolin and acarbose. Findings of molecular interactions, molecular dynamics study, metabolism, and biological activity prediction proved bromelain as a potential alpha-glucosidase inhibitor. Thus, bromelain might be helpful as an insulin-independent therapeutic molecule towards controlling and managing diabetes mellitus type 2.

Cochlear implantation in common cavity deformity: a systematic review.

PURPOSE: Cochlear implantation became a valid hearing rehabilitation option in common cavity deformity. This study aimed to assess the audiological and speech outcomes of cochlear implantation in common cavity deformity patients and to address the surgical aspect used in this population. METHODS: A comprehensive systematic literature review based on preferred reporting items for systematic reviews and meta-analyses (PRISMA) guideline from database inception through April 2020. Eighteen published articles including 138 patients with common cavity deformity met the inclusion criteria. These articles studied the surgical techniques and the audiological outcomes of cochlear implantation in patients with common cavity deformity in English language. RESULTS: Trans-mastoid labyrinthotomy was the common surgical approach in these patients. The average speech intelligibility rating and categories of auditory performance scores in common cavity deformity were lower than in normal cochlea subjects (p < 0.05), and non-significant (p > 0.05) compared with other types of inner ear malformations. CONCLUSION: Patients with common cavity deformity who underwent cochlear implantation showed a beneficial audiological and speech outcome. However, their performance is highly variable. Therefore, pre-operative counseling of the parents is necessary. The surgical approaches should be individualized according to clinical, radiological, and surgical findings.

Transradial versus transfemoral access for cardiac catheterization: a nationwide pilot study of training preferences and expertise in The United States.

BACKGROUND: The objective was to assess current training preferences, expertise, and comfort with transfemoral access (TFA) and transradial access (TRA) amongst cardiovascular training fellows and teaching faculty in the United States. As TRA continues to dominate the field of interventional cardiology, there is a concern that trainees may become less proficient with the femoral approach. METHODS: A detailed questionnaire was sent out to academic General Cardiovascular and Interventional Cardiology training programs in the United States. Responses were sought from fellows-in-training and faculty regarding preferences and practice of TFA and TRA. Answers were analyzed for significant differences between trainees and trainers. RESULTS: A total of 125 respondents (75 fellows-in-training and 50 faculty) completed and returned the survey. The average grade of comfort for TFA, on a scale of 0 to 10 (10 being most comfortable), was reported to be 6 by fellows-in-training and 10 by teaching faculty (p < 0.001). TRA was the first preference in 95% of the fellows-in-training compared to 69% of teaching faculty (p 0.001). While 62% of fellows believed that they would receive the same level of training as their trainers by the time they graduate, only 35% of their trainers believed so (p 0.004). CONCLUSION: The shift from TFA to radial first has resulted in significant concern among cardiovascular fellows-in training and the faculty regarding training in TFA. Cardiovascular training programs must be cognizant of this issue and should devise methods to assure optimal training of fellows in gaining TFA and managing femoral access-related complications.

Performance of cochlear implant recipients fitted with triphasic pulse patterns.

PURPOSE: To assess the effect of triphasic pulse pattern stimulation strategy on the audiological performance of cochlear implant recipients with unintended facial nerve stimulation (FNS), and to compare the audiological and speech outcomes before and after switching to triphasic stimulation. METHODS: A retrospective study of patients who have changed their fitting maps from biphasic to triphasic pulse pattern stimulation because of FNS after cochlear implantation (CI). All identified patients with FNS after CI from 2017 to 2019 were included in this study. The medical records of 11 patients (16 ears) were queried for demographic and radiological data, pure tone audiometry, speech reception thresholds, speech discrimination score at 65 dB, maximum comfortable levels, thresholds, and dynamic range. Then, these parameters were compared in the two conditions, biphasic and triphasic. RESULTS: Using triphasic pulse stimulation only or combined with switch-off of few channels, complete resolution of FNS was achieved. Triphasic pulse pattern stimulation was associated with better speech discrimination scores (75.25 ± 26.13%) compared to the biphasic pulse (58.25 ± 26.13%). This triphasic strategy also showed higher maximum comfortable levels (36.62 ± 1.63 qu) than biphasic strategy (31.58 ± 2.5 qu). Moreover, the dynamic range was wider using triphasic pulse strategy. In general, the triphasic pulse pattern resulted in successful suppression of facial nerve stimulation with suitable maximum comfortable levels and better speech discrimination. CONCLUSION: Triphasic pulse pattern stimulation is an appropriate tool in controlling FNS following cochlear implantation with wider dynamic range. We recommend that all patients with facial nerve stimulation after CI surgery be switched to a triphasic pulse program prior to considering further surgery.

Comparative Chemical Profiles of the Essential Oils from Different Varieties of Psidium guajava L.

Guava (Psidium guajava) leaves are commonly used in the treatment of diseases. They are considered a waste product resulting from guava cultivation. The leaves are very rich in essential oils (EOs) and volatiles. This work represents the detailed comparative chemical profiles of EOs derived from the leaves of six guava varieties cultivated in Egypt, including Red Malaysian (RM), El-Qanater (EQ), White Indian (WI), Early (E), El-Sabahya El-Gedida (ESEG), and Red Indian (RI), cultivated on the same farm in Egypt. The EOs from the leaves of guava varieties were extracted by hydro-distillation and analyzed with GC-MS. The EOs were categorized in a holistic manner using chemometric tools. The hydro-distillation of the samples yielded 0.11-0.48% of the EO (v/w). The GC-MS analysis of the extracted EOs showed the presence of 38 identified compounds from the six varieties. The sesquiterpene compounds were recorded as main compounds of E, EQ, ESEG, RI, and WI varieties, while the RM variety attained the highest content of monoterpenes (56.87%). The sesquiterpenes, ß-caryophyllene (11.21-43.20%), and globulol (76.17-26.42%) were detected as the major compounds of all studied guava varieties, while trans-nerolidol (0.53-10.14) was reported as a plentiful compound in all of the varieties except for the RM variety. A high concentration of D-limonene was detected in the EOs of the RM (33.96%), WI (27.04%), and ESEG (9.10%) varieties. These major compounds were consistent with those reported for other genotypes from different countries. Overall, the EOs' composition and the chemometric analysis revealed substantial variations among the studied varieties that might be ascribed to genetic variability, considering the stability of the cultivation and climate conditions. Therefore, this chemical polymorphism of the studied varieties supports that these varieties could be considered as genotypes of P. guajava. It is worth mentioning here that the EOs, derived from leaves considered to be agricultural waste, of the studied varieties showed that they are rich in biologically active compounds, particularly ß-caryophyllene, trans-nerolidol, globulol, and D-limonene. These could be considered as added value for pharmacological and industrial applications. Further study is recommended to confirm the chemical variations of the studied varieties at a molecular level, as well as their possible medicinal and industrial uses.

Prospective Double-Blinded Randomized Field-Based Clinical Trial of Metoclopramide and Ibuprofen for the Treatment of High Altitude Headache and Acute Mountain Sickness.

INTRODUCTION: High altitude headache (HAH) and acute mountain sickness (AMS) are common pathologies at high altitudes. There are similarities between AMS and migraine headaches, with nausea being a common symptom. Several studies have shown ibuprofen can be effective for AMS prophylaxis, but few have addressed treatment. Metoclopramide is commonly administered for migraine headaches but has not been evaluated for HAH or AMS. We aimed to evaluate metoclopramide and ibuprofen for treatment of HAH and AMS. METHODS: We performed a prospective, double-blinded, randomized, field-based clinical trial of metoclopramide and ibuprofen for the treatment of HAH and AMS in 47 adult subjects in the Mount Everest region of Nepal. Subjects received either 400 mg ibuprofen or 10 mg metoclopramide in a 1-time dose. Lake Louise Score (LLS) and visual analog scale of symptoms were measured before and at 30, 60, and 120 min after treatment. RESULTS: Subjects in both the metoclopramide and ibuprofen arms reported reduced headache severity and nausea compared to pretreatment values at 120 min. The ibuprofen group reported 22 mm reduction in headache and 6 mm reduction in nausea on a 100 mm visual analog scale at 120 min. The metoclopramide group reported 23 mm reduction in headache and 14 mm reduction in nausea. The ibuprofen group reported an average 3.5-point decrease on LLS, whereas the metoclopramide group reported an average 2.0-point decrease on LLS at 120 min. CONCLUSIONS: Metoclopramide and ibuprofen may be effective alternative treatment options in HAH and AMS, especially for those patients who additionally report nausea.

Phase transitions in the assembly of multivalent signalling proteins.

Cells are organized on length scales ranging from ångström to micrometres. However, the mechanisms by which ångström-scale molecular properties are translated to micrometre-scale macroscopic properties are not well understood. Here we show that interactions between diverse synthetic, multivalent macromolecules (including multi-domain proteins and RNA) produce sharp liquid-liquid-demixing phase separations, generating micrometre-sized liquid droplets in aqueous solution. This macroscopic transition corresponds to a molecular transition between small complexes and large, dynamic supramolecular polymers. The concentrations needed for phase transition are directly related to the valency of the interacting species. In the case of the actin-regulatory protein called neural Wiskott-Aldrich syndrome protein (N-WASP) interacting with its established biological partners NCK and phosphorylated nephrin, the phase transition corresponds to a sharp increase in activity towards an actin nucleation factor, the Arp2/3 complex. The transition is governed by the degree of phosphorylation of nephrin, explaining how this property of the system can be controlled to regulatory effect by kinases. The widespread occurrence of multivalent systems suggests that phase transitions may be used to spatially organize and biochemically regulate information throughout biology.

Predictable prosthesis length on a high-resolution CT scan before a stapedotomy.

OBJECTIVE: (1) To assess the correlation between preoperative high-resolution CT (HRCT) imaging measurement from the long process of the incus to the footplate and the length of intraoperative selected prosthesis. (2) To determine if HRCT has a predictive value of prolapsed facial nerve during stapedotomy. MATERIALS AND METHODS: We evaluated in our tertiary care center, in a retrospective case series, 94 patients undergoing primary stapedotomy. Preoperative temporal bone HRCT scans were reformatted in the plane of the stapes to measure on the same section the distance between the long process of the incus and the footplate. Measurement was performed by otolaryngology resident and neurotologist. We analyze the interobserver correlation and the mean length measured on the HRCT to the selected prosthesis size intraoperatively. RESULTS: Mean HRCT measurement of the incus long process/footplate distance assessed by the otolaryngology resident and neurotologist was 4.34 and 4.38 mm, respectively. Interobserver correlation was statistically significant [intraclass correlation coefficient (ICC) of 0.679 (p < 0.001)]. Mean selected prosthesis length intraoperatively was 4.36 mm. Correlation between the mean selected length prosthesis and the mean HRCT measurement was also statistically significant [ICC of 0.791 (p < 0.001)]. Postoperatively, a statistical improvement was shown in air conduction (p < 0.001), bone conduction (p < 0.001) and air-bone gap reduction (p < 0.001). 2 cases of facial nerve covering one-half of the oval window were identified by HRCT and confirmed intraoperatively. CONCLUSION: HRCT is a valuable tool to predict preoperatively the length of the stapedotomy prosthesis. Moreover, it might be helpful to identify a potential prolapsed facial nerve, to confirm the diagnosis of otosclerosis and to rule out other abnormalities. Ultimately, it may optimize the stapedotomy procedure planning.

Video head impulse test: a review of the literature.

Video head impulse test (vHIT) is a new testing which able to identify the overt and covert saccades and study the gain of vestibulo-ocular reflex (VOR) of each semicircular canal. The aim of this study is to review the clinical use of vHIT in patients with vestibular disorders in different diseases. PubMed and Cochrane databases were searched for all articles that defined vHIT, compared vHIT with another clinical test, and studied the efficacy of vHIT as diagnostic tools with vestibular disease. 37 articles about vHIT were reviewed. All articles studied the vHIT in English and French languages up to May 2015 were included in the review. Editorial articles or short comments, conference abstracts, animal studies, and language restriction were excluded from the review. Four systems were used in the literature to do the vHIT. vHIT is physiological quick test, which studied the VOR at high frequency of each semicircular canal by calculating the duration ratio between the head impulse and gaze deviation. vHIT is more sensitive than clinical head impulse test (cHIT), especially in patient with isolated covert saccades. vHIT test is diagnostic of vestibular weakness by gain reduction and the appearance of overt and covert saccades. If the vHIT is normal, then caloric test is mandatory to rule out a peripheral origin of vertigo. It is recommended to test each semicircular canal, as isolated vertical canal weakness was identified in the literature. More investigation would be required to determine the evolution of the VOR gain with the progression of the vestibular disease.

The use of magnetically controlled growing rod device for pediatric scoliosis.

OBJECTIVE: To study the safety and efficacy of an innovative device using distraction-based magnetically controlled growing rods (MCGR) for the treatment of pediatric scoliosis. METHODS: This is an evidence-based systematic review of literature for the surgical management of patients with pediatric scoliosis using MCGR technique. Six clinical studies regarding the use of MCGR were included in this review, with a total of 68 patients, and mean age of 8.38 years. The dual-rod (DR) technique of rod construct with MCGR was used in 33.85% and the single-rod (SR) in 66.15% of the patients. RESULTS: The mean preoperative main coronal curve for the DR was 65.9°, and for the SR was 69.6° (p>0.05). At the latest follow-up, it was 36.8° for DR and 43.0 degrees for SR (p<0.05). The mean preoperative T1 - S1 spinal length was 298.7 mm for the DR and 303.5 mm for the SR group (p<0.05). According to the latest follow-up, using the DR construct, the spinal length increased to 347 mm with 13.92% of total lengthening; and using the SR construct, the average lengthening was 339 mm, with 10.48% of total lengthening (p<0.05). Postoperative complications were similar, 25% in DR and 31.57% in the SR group (p>0.05). CONCLUSION: Level IV of medical evidence supports the use of MCGR as a safe and effective alternative for the treatment of severe pediatric scoliosis. Recommendation Grade C supports the role of MCGR with DR construct as an option to achieve a better correction of the scoliotic curve and to maximize the postoperative T1 - S1 spinal length.