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BACKGROUND: This study aimed to identify the density of mononuclear cells (MNCs) and CD34+ cells in the bone marrow of patients with three neurologic conditions. METHODS: The study included 88 patients with three neurologic conditions: 40 with cerebral palsy (CP) due to oxygen deprivation (OD), 23 with CP related to neonatal icterus (NI), and 25 with neurological sequelae after traumatic brain injury. Bone marrow aspiration was conducted from the patients' bilateral anterior iliac crest under general anesthesia in an operating theater. MNCs were isolated by Ficoll gradient centrifugation and then infused intrathecally. RESULTS: There was a significant difference in the average MNC per ml and percentage of CD34+ cells by the type of disease, age group, and infusion time (p value < 0.05). The multivariable regression model showed the percentage of CD34+ association with the outcome (gross motor function 88 items- GMFM-88) in patients with CP. CONCLUSIONS: The density of MNCs was 5.22 million cells per mL and 5.03% CD34+ cells in patients with three neurologic conditions. The highest density of MNCs in each ml of bone marrow was found in patients with CP due to OD, whereas the percentage of CD34+ cells was the highest among patients with CP related to NI.
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Medula Óssea , Paralisia Cerebral , Recém-Nascido , Humanos , Antígenos CD34 , Transplante de Medula Óssea , Células da Medula ÓsseaRESUMO
An absolute encoder based on vision system nanoGPS OxyO was developed by HORIBA France. This encoder provides three types of position information, namely, two inplane co-ordinates and inplane angular orientation. This paper focuses on the characterization of its angular performance. To this aim, the nanoGPS OxyO system was compared with the national angle standard of the National Metrology Institute of Italy (INRIM) that had evaluated accuracy of about 0.1 µrad. The effect of image size and illumination conditions on angular measurements was studied. Precision better than 10 µrad and accuracy better than 63 µrad over 2π rotation were demonstrated. Moreover, the application of nanoGPS OxyO to the characterization of rotation bearing is presented. Small deviations from pure rotational behavior were evidenced that would have not been possible using laser interferometers. As a consequence of its accuracy and versatility, the nanoGPS OxyO encoder is expected to be useful for laboratory experiments and quality-control tasks.
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BACKGROUND: Quality of life (QOL) is an important factor in evaluating the effectiveness of treatment in children with cerebral palsy (CP). The aim of this study was to evaluate the effects of autologous bone marrow mononuclear cells (BM MNCs) on the QOL of children with CP. METHODS: From December 2015 to December 2016, 30 children with CP aged from 2 to 15 years received two intrathecal infusions of BM MNCs, one at baseline and the other 3 months later, at Vinmec International Hospital. The motor function and muscle tone of the patients were evaluated using the Gross Motor Function Measure (GMFM)-88 and Modified Ashworth Score, respectively. Their QOL was assessed at baseline and 6 months after the first BM MNC transplant using the Vietnamese version of the Cerebral Palsy Quality of Life Questionnaire for children (CP QOL-Child)-the parental proxy report, which comprises seven domains. Nineteen mothers (mean age: 32.9±4.9 years) and 11 fathers (mean age: 36.1±6.8 years) were invited to complete the CP QOL-Child assessment before and after the transplantations, Paired t-tests and multivariate regression analyses were used to evaluate the changes in QOL and GMFM scores and to identify the key factors correlated with the QOL score. RESULTS: Significant changes were observed in the children's gross motor function and muscle spasticity, as evidenced by the GMFM-88 total score, scores for each of its domains, the GMFM-66 percentile and the muscle tone (P < 0.001). Six months after the transplantations, the QOL scores of children with CP were markedly increased (P < 0.001) for all the domains, except for the domain of access to services. In the multivariate regression analysis, significant associations were found between higher age of children and higher QOL except for feeling about functioning and pain and impact of disability domains. Gross Motor Function Classification System (GMFCS) level was negatively correlated with the score of pain and impact of disability domain, while the GMFM-88 scores were positively correlated with the QOL in terms of feelings about functioning and family health domain (P < 0.05). CONCLUSION: The QOL of the children with CP was noticeably improved 6 months after BM MNC transplantation and was accompanied by improvements in gross motor function and muscle tone. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02574923 . Registered on October 14, 2015.
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Transplante de Medula Óssea/psicologia , Cuidadores/psicologia , Paralisia Cerebral/psicologia , Paralisia Cerebral/cirurgia , Pais/psicologia , Qualidade de Vida/psicologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Inquéritos e QuestionáriosRESUMO
To adopt an efficient approach of identifying rare variants possibly related to Hirschsprung disease (HSCR), a pilot study was set up to evaluate the performance of a newly designed protocol for next generation targeted resquencing. In total, 20 Chinese HSCR patients and 20 Chinese sex-matched individuals with no HSCR were included, for which coding sequences (CDS) of 62 genes known to be in signaling pathways relevant to enteric nervous system development were selected for capture and sequencing. Blood DNAs from eight pools of five cases or controls were enriched by PCR-based RainDance technology (RDT) and then sequenced on a 454 FLX platform. As technical validation, five patients from case Pool-3 were also independently enriched by RDT, indexed with barcode and sequenced with sufficient coverage. Assessment for CDS single nucleotide variants showed DNA pooling performed well (specificity/sensitivity at 98.4%/83.7%) at the common variant level; but relatively worse (specificity/sensitivity at 65.5%/61.3%) at the rare variant level. Further Sanger sequencing only validated five out of 12 rare damaging variants likely involved in HSCR. Hence more improvement at variant detection and sequencing technology is needed to realize the potential of DNA pooling for large-scale resequencing projects.
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Povo Asiático/genética , Técnicas de Genotipagem/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Doença de Hirschsprung/genética , Transdução de Sinais/genética , Sistema Nervoso Entérico/fisiologia , Feminino , Humanos , Masculino , Projetos Piloto , Polimorfismo de Nucleotídeo Único/genética , Sensibilidade e Especificidade , Transdução de Sinais/fisiologiaRESUMO
We report emission spectrum measurements on single YxEu(1-x)VO4 nanoparticles. The inhomogeneous widths of the emission peaks are identical for single nanoparticles and for ensembles of nanoparticles, while being broader than those of the bulk material. This indicates that individual nanoparticles are identical in terms of the distribution of different local Eu3+ sites due to crystalline defects and confirms their usability as identical, single-particle oxidant biosensors. Moreover, we report a 465 nm solid-state laser based on sum-frequency mixing that provides a compact, efficient solution for direct Eu3+ excitation of these nanoparticles. Both these two aspects should broaden the scope of Eu-doped nanoparticle applications.
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Systemic lupus erythematosus (SLE) is a chronic autoimmune disease in which multiple organs are damaged by the immune system. Although standard treatment options such as hydroxychloroquine (HCQ), glucocorticoids (GCs), and other immunosuppressive or immune-modulating agents can help to manage symptoms, they do not offer a cure. Hence, there is an urgent need for the development of novel drugs and therapies. In recent decades, cell therapies have been used for the treatment of SLE with encouraging results. Hematopoietic stem cell transplantation, mesenchymal stem cells, regulatory T (Treg) cell, natural killer cells, and chimeric antigen receptor T (CAR T) cells are advanced cell therapies which have been developed and evaluated in clinical trials in humans. In clinical application, each of these approaches has shown advantages and disadvantages. In addition, further studies are necessary to conclusively establish the safety and efficacy of these therapies. This review provides a summary of recent clinical trials investigating cell therapies for SLE treatment, along with a discussion on the potential of other cell-based therapies. The factors influencing the selection of common cell therapies for individual patients are also highlighted.
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Background: Subdural hematoma following spinal anesthesia for cesarean delivery is a rare complication. Surgical removal of the hematoma is the standard treatment. However, there are still many patients who suffer permanent nerve damage of varying degrees after surgery. Cell therapy has recently shown great potential for treating nerve damage. Case presentation: This report described a case of paraplegia due to an epidural hematoma occurring after spinal anesthesia for cesarean section. The patient underwent surgery to remove the hematoma and rehabilitation afterward. However, no improvement was noted. Paralysis of the lower extremities associated with urinary retention and constipation persisted. The patient received three administrations of cell infusion: the first time with autologous bone marrow-derived mononuclear cells and the following two with autologous adipose mesenchymal/stromal cells. After three cell infusions, the patient was able to walk and could urinate and defecate voluntarily. Sensory and motor function were improved and MRI showed a decrease in adherence of the nerve roots and spinal cord. Conclusions: Our results demonstrated that cell therapy may ameliorate paralysis of the lower extremities as well as fecal and urinary function following spinal hematoma associated with spinal anesthesia.
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BACKGROUND: Hyperactive coagulation might cause dangerous complications such as portal vein thrombosis and pulmonary embolism after mesenchymal stem/stromal cell (MSC) therapy. Tissue factor (TF), an initiator of the extrinsic coagulation pathway, has been suggested as a predictor of this process. METHODS: The expression of TF and other pro- and anticoagulant genes was analyzed in xeno- and serum-free manufactured MSCs. Furthermore, culture factors affecting its expression in MSCs were investigated. Finally, coagulation tests of fibrinogen, D-dimer, aPPTs, PTs, and TTs were measured in patient serum after umbilical cord (UC)-MSC infusions to challenge a potential connection between TF expression and MSC-induced coagulant activity. RESULTS: Xeno- and serum-free cultured adipose tissue and UC-derived MSCs expressed the highest level of TF, followed by those from dental pulp, and the lowest expression was observed in MSCs of bone marrow origin. Environmental factors such as cell density, hypoxia, and inflammation impact TF expression, so in vitro analysis might fail to reflect their in vivo behaviors. MSCs also expressed heterogeneous levels of the coagulant factor COL1A1 and surface phosphatidylserine and anticoagulant factors TFPI and PTGIR. MSCs of diverse origins induced fibrin clots in healthy plasma that were partially suppressed by an anti-TF inhibitory monoclonal antibody. Furthermore, human umbilical vein endothelial cells exhibited coagulant activity in vitro despite their negative expression of TF and COL1A1. Patients receiving intravenous UC-MSC infusion exhibited a transient increase in D-dimer serum concentration, while this remained stable in the group with intrathecal infusion. There was no correlation between TF expression and D-dimer or other coagulation indicators. CONCLUSIONS: The study suggests that TF cannot be used as a solid biomarker to predict MSC-induced hypercoagulation. Local administration, prophylactic intervention with anticoagulation drugs, and monitoring of coagulation indicators are useful to prevent thrombogenic events in patients receiving MSCs. Trial registration NCT05292625. Registered March 23, 2022, retrospectively registered, https://www. CLINICALTRIALS: gov/ct2/show/NCT05292625?term=NCT05292625&draw=2&rank=1 . NCT04919135. Registered June 9, 2021, https://www. CLINICALTRIALS: gov/ct2/show/NCT04919135?term=NCT04919135&draw=2&rank=1 .
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Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Trombose , Humanos , Tromboplastina/genética , Tromboplastina/metabolismo , Células Cultivadas , Trombose/genética , Células-Tronco Mesenquimais/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Anticoagulantes , Cordão UmbilicalRESUMO
Investigations of the in-plane positioning capabilities of microscopes using machine-readable encoded patterned scales are presented. The scales have patterns that contain absolute position information, and adequate software accurately determines the in-plane position from the scale images captured by the microscope camera. This makes in-plane positioning experiments simple and fast. The scales and software used in this study are commercially available. We investigated different microscopy systems and found that positioning performance is a system issue that is not determined solely by stage performance. In some cases, our experiments revealed software or hardware glitches that limited the positioning performance, which we easily fixed. We have also shown that it is possible to investigate vibrations using this approach and quantify their impact on image blurring. This is, for example, useful for experimentally determining the settling time after a stage movement.
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Aim: To present outcomes of single trocar thoracoscopic surgery in the treatment of pleural empyema (PE) in children. Patients and Methods: The thoracoscopic surgery was performed using a single trocar inserted through the fifth intercostal space. A conventional rigid scope with a working channel was used. Pleural fluid was aspirated, followed by debridement and ablation of all septa using one instrument through the working channel. Results: Sixty patients from 1 month to 14 years of age underwent surgery without any intraoperative complications or death. The mean operative time was 67 ± 21 minutes. There was no conversion to open thoracotomy. Postoperative complications occurred in 4 patients. Reoperation was required in 1 patient. Mean duration of postoperative hospitalization was 15 ± 9 days. Follow-up was obtained in 57 patients and resulted in normal clinical and chest X-ray findings in all patients. Conclusion: Single trocar thoracoscopic operation is safe, feasible, and effective in the treatment of PE in children. A future study with control group is required to draw accurate conclusions.
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Empiema Pleural , Toracoscopia , Humanos , Criança , Empiema Pleural/cirurgia , Toracotomia , Desbridamento , Instrumentos Cirúrgicos , Cirurgia Torácica Vídeoassistida , Estudos RetrospectivosRESUMO
Continuing evolution of highly pathogenic (HP) H5N1 influenza viruses in wild birds with transmission to domestic poultry and humans poses a pandemic threat. There is an urgent need for a simple and rapid serological diagnostic assay which can differentiate between antibodies to seasonal and H5N1 strains and that could provide surveillance tools not dependent on virus isolation and nucleic acid technologies. Here we describe the establishment of H5N1 SeroDetect enzyme-linked immunosorbent assay (ELISA) and rapid test assays based on three peptides in HA2 (488-516), PB1-F2 (2-75), and M2e (2-24) that are highly conserved within H5N1 strains. These peptides were identified by antibody repertoire analyses of H5N1 influenza survivors in Vietnam using whole-genome-fragment phage display libraries (GFPDLs). To date, both platforms have demonstrated high levels of sensitivity and specificity in detecting H5N1 infections (clade 1 and clade 2.3.4) in Vietnamese patients as early as 7 days and up to several years postinfection. H5N1 virus-uninfected individuals in Vietnam and the United States, including subjects vaccinated with seasonal influenza vaccines or with confirmed seasonal virus infections, did not react in the H5N1-SeroDetect assays. Moreover, sera from individuals vaccinated with H5N1 subunit vaccine with moderate anti-H5N1 neutralizing antibody titers did not react positively in the H5N1-SeroDetect ELISA or rapid test assays. The simple H5N1-SeroDetect ELISA and rapid tests could provide an important tool for large-scale surveillance for potential exposure to HP H5N1 strains in both humans and birds.
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Virus da Influenza A Subtipo H5N1/imunologia , Influenza Humana/diagnóstico , Proteínas Virais/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/imunologia , Criança , Pré-Escolar , Estudos de Coortes , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Técnicas Imunoenzimáticas , Influenza Humana/imunologia , Influenza Humana/virologia , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/imunologia , Biblioteca de Peptídeos , Sensibilidade e Especificidade , Testes Sorológicos , Adulto JovemRESUMO
AIM: To evaluate the safety and early outcomes of autologous bone marrow mononuclear cell (BMMNC) infusion for liver cirrhosis due to biliary atresia (BA) after Kasai operation. METHODS: An open-label clinical trial was performed from January 2017 to December 2019. Nineteen children with liver cirrhosis due to BA after Kasai operation were included. Bone marrow was harvested through anterior iliac crest puncture under general anesthesia. Mononuclear cells (MNCs) were isolated by Ficoll gradient centrifugation and then infused into the hepatic artery. The same procedure was repeated 6 months later. Serum bilirubin, albumin, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and prothrombin time were monitored at baseline, 3 months, 6 months, and 12 months after the first transplantation. Esophagoscopies and liver biopsies were performed in patients whose parents provided consent. Mixed-effect analysis was used to evaluate the changes in Pediatric End-Stage Liver Disease (PELD) scores. RESULTS: The average MNC and CD34+ cell counts per kg body weight were 50.1 ± 58.5 × 106/kg and 3.5 ± 2.8 × 106 for the first transplantation and 57.1 ± 42.0 × 106/kg and 3.7 ± 2.7 × 106 for the second transplantation. No severe adverse events associated with the cell therapy were observed in the patients. One patient died 5 months after the first infusion at a provincial hospital due to the rupture of esophageal varices, while 18 patients survived. Liver function was maintained or improved after infusion, as assessed by biochemical tests. The severity of the disease reduced markedly, with a significant reduction in PELD scores. CONCLUSION: Autologous BMMNC administration for liver cirrhosis due to BA is safe and may maintain or improve liver function. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03468699. Name of the registry: Vinmec Research Institute of Stem Cell and Gene Technology. https://clinicaltrials.gov/ct2/show/NCT03468699?cond=biliary+atresia&cntry=VN&draw=2&rank=2 . Registered on March 16, 2018. The trial results will also be published according to the CONSORT statement at conferences and reported in peer-reviewed journals.
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Atresia Biliar , Doença Hepática Terminal , Atresia Biliar/cirurgia , Medula Óssea , Criança , Humanos , Cirrose Hepática/terapia , Índice de Gravidade de DoençaRESUMO
Hormone imbalance and female sexual dysfunction immensely affect perimenopausal female health and quality of life. Hormone therapy can improve female hormone deficiency, but long-term use increases the risk of cardiovascular diseases and cancer. Therefore, it is necessary to develop a novel effective treatment to achieve long-term improvement in female general and sexual health. This study reviewed factors affecting syndromes of female sexual dysfunction and its current therapy options. Next, the authors introduced research data on mesenchymal stromal cell/mesenchymal stem cell (MSC) therapy to treat female reproductive diseases, including Asherman's syndrome, premature ovarian failure/primary ovarian insufficiency, and vaginal atrophy. Among adult tissue-derived MSCs, adipose tissue-derived stem cells (ASCs) have emerged as the most potent therapeutic cell therapy due to their abundant presence in the stromal vascular fraction of fat, high proliferation capacity, superior immunomodulation, and strong secretion profile of regenerative factors. Potential mechanisms and side effects of ASCs for the treatment of female sexual dysfunction will be discussed. Our phase I clinical trial has demonstrated the safety of autologous ASC therapy for women and men with sexual hormone deficiency. We designed the first randomized controlled crossover phase II trial to investigate the safety and efficacy of autologous ASCs to treat female sexual dysfunction in perimenopausal women. Here, we introduce the rationale, trial design, and methodology of this clinical study. Because aging and metabolic diseases negatively impact the bioactivity of adult-derived MSCs, this study will use ASCs cultured in physiological oxygen tension (5%) to cope with these challenges. A total of 130 perimenopausal women with sexual dysfunction will receive two intravenous infusions of autologous ASCs in a crossover design. The aims of the proposed study are to evaluate 1) the safety of cell infusion based on the frequency and severity of adverse events/serious adverse events during infusion and follow-up and 2) improvements in female sexual function assessed by the Female Sexual Function Index (FSFI), the Utian Quality of Life Scale (UQOL), and the levels of follicle-stimulating hormone (FSH) and estradiol. In addition, cellular aging biomarkers, including plasminogen activator inhibitor-1 (PAI-1), p16 and p21 expression in T cells and the inflammatory cytokine profile, will also be characterized. Overall, this study will provide essential insights into the effects and potential mechanisms of ASC therapy for perimenopausal women with sexual dysfunction. It also suggests direction and design strategies for future research.
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Anti-N-methyl-d-aspartate (NMDA) receptor encephalitis is caused by altered patient immune reactions. This study reports the first patient with severe neurologic sequelae after NMDA receptor encephalitis treated with allogeneic umbilical cord-derived mesenchymal stem/stromal cells (UC-MSCs). A 5-year-old girl was diagnosed with NMDA receptor encephalitis and treated with immunosuppressive medicaments and intravenous immunoglobulin (IVIG). Despite intensive therapy, the patient's condition worsened so that allogenic UC-MSC therapy was contemplated. The patient received three intrathecal infusions of xeno- and serum-free cultured UC-MSCs at a dose of 106 cells/kg. At baseline and after each UC-MSC administration, the patient was examined by the German Coma Recovery Scale (CRS), the Gross Motor Function Classification System (GMFCS), the Gross Motor Function Measure-88 (GMFM-88), the Manual Ability Classification System (MACS), the Modified Ashworth Scale, and the Denver II test. Before cell therapy, she was in a permanent vegetative state with diffuse cerebral atrophy. Her cognition and motor functions improved progressively after three UC-MSC infusions. At the last visit, she was capable of walking, writing, and counting numbers. Control of urinary and bowel functions was completely recovered. Cerebral atrophy was reduced on brain magnetic resonance imaging (MRI). Overall, the outcomes of this patient suggest a potential cell therapy for autoimmune encephalitis and its neurological consequences.
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Encefalite Antirreceptor de N-Metil-D-Aspartato , Células-Tronco Mesenquimais , Encefalite Antirreceptor de N-Metil-D-Aspartato/complicações , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Encefalite Antirreceptor de N-Metil-D-Aspartato/terapia , Atrofia/complicações , Pré-Escolar , Progressão da Doença , Feminino , Humanos , Receptores de N-Metil-D-Aspartato/uso terapêutico , Cordão UmbilicalRESUMO
BACKGROUND: We have observed an increased expression of negative markers in some clinical-grade, xeno- and serum-free cultured adipose-derived mesenchymal stem/stromal cell (ADMSC) samples. It gave rise to concern that xeno- and serum-free conditions might have unexpected effects on human ADMSCs. This study aims to test this hypothesis for two xeno- and serum-free media, PowerStem MSC1 media (PS) and StemMACS MSC Expansion Media (SM), that support the in vitro expansion of ADMSCs. METHODS: We investigated the expression of negative markers in 42 clinical-grade ADMSC samples expanded in PS. Next, we cultured ADMSCs from seven donors in PS and SM and examined their growth and colony-forming ability, surface marker expression, differentiation, cell cycle and senescence, as well as genetic stability of two passages representing an early and late passage for therapeutic MSCs. RESULTS: 15 of 42 clinical-grade PS-expanded ADMSC samples showed an increased expression of negative markers ranging from 2.73% to 34.24%, which positively correlated with the age of donors. This rise of negative markers was related to an upregulation of Human Leukocyte Antigen - DR (HLA-DR). In addition, the PS-cultured cells presented decreased growth ability, lower frequencies of cells in S/G2/M phases, and increased ß-galactosidase activity in passage 7 suggesting their senescent feature compared to those grown in SM. Although MSCs of both PS and SM cultures were capable of multilineage differentiation, the PS-cultured cells demonstrated chromosomal abnormalities in passage 7 compared to the normal karyotype of their SM counterparts. CONCLUSIONS: These findings suggest that the SM media is more suitable for the expansion of therapeutic ADMSCs than PS. The study also hints a change of ADMSC features at more advanced passages and with increased donor's age. Thus, it emphasizes the necessity to cover these aspects in the quality control of therapeutic MSC products.
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Antígenos HLA-DR , Células-Tronco Mesenquimais , Diferenciação Celular/genética , Proliferação de Células/genética , Meios de Cultura Livres de Soro/metabolismo , Meios de Cultura Livres de Soro/farmacologia , Antígenos HLA-DR/metabolismo , HumanosRESUMO
BACKGROUND: Sexual functional deficiency occurs at some point in life and becomes a problematic issue in middle-aged adulthood. Regenerative medicine, especially mesenchymal stem cell (MSC) transplantation, has developed extensively, with preclinical and clinical trials emphasizing the benefits of stem cell therapy for restoration of sexual deficiency. This study was designed to develop a new therapeutic stem cell treatment for people with sexual functional deficiency. METHODS: Thirty-one patients, including 15 males and 16 females with a medical history of reduced sexual activity, met the inclusion criteria and were enrolled in the study, phase I/IIa clinical trial with a 12-month follow-up. Adipose tissue-derived mesenchymal stem/stromal cells (ADSC) were isolated by type I collagenase digestion and cultured at the Stem Cell Core Facility under ISO 14644-1. Each participant received 1 million cells/kg of body weight via the intravenous route. Safety was evaluated by assessing the occurrence of adverse events or severe adverse events. Efficacy was assessed in males by monitoring testosterone levels and administering the International Index of Erectile Function (IIEF) questionnaire and in females by monitoring anti-Mullerian hormone (AMH), estradiol (E2), and follicle-stimulating hormone (FSH) levels and administering the Female Sexual Functioning Index (FSFI) questionnaire at baseline and 3-, 6-, and 12-months post-transplantation. RESULTS: There was no occurrence of severe adverse events after ADSC administration in our study. Post-transplantation sexual satisfaction was observed in all patients enrolled in this study. Testosterone levels in males increased soon after transplantation and were maintained at high levels for up to 6 months before decreasing again at the 12-month follow-up. No significant changes in AMH, FSH or E2 levels were recorded in female patients. CONCLUSIONS: Autologous ADSC infusion is a potential therapeutic option for patients with reduced sexual activity, especially for male patients. TRIAL REGISTRATION: ClinicalTrials.gov. NCT03346967, Registered November 20, 2017.
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Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Adulto , Feminino , Humanos , Masculino , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Células-Tronco Mesenquimais/metabolismo , Pessoa de Meia-Idade , Medicina Regenerativa , Comportamento Sexual , Transplante AutólogoRESUMO
The aim of this study was to evaluate the safety and efficacy of autologous bone marrow mononuclear cell transplantation combined with educational intervention for children with autism spectrum disorder. An open-label clinical trial was performed from July 2017 to August 2019 at Vinmec International Hospital, Hanoi, Vietnam. Thirty children who fulfilled the autism criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and had Childhood Autism Rating Scale (CARS) scores >37 were selected. Bone marrow was harvested by anterior iliac crest puncture under general anesthesia. The volume collected was as follows: 8 mL/kg for patients under 10 kg (80 mL + [body weight in kg - 10] × 7 mL) for patients above 10 kg. Mononuclear cells were isolated with a Ficoll gradient and then infused intrathecally. The same procedure was repeated 6 months later. After the first transplantation, all patients underwent 8 weeks of educational intervention based on the Early Start Denver Model. There were no severe adverse events associated with transplantation. The severity of autism spectrum disorder (ASD) was significantly reduced, with the median CARS score decreasing from 50 (range 40-55.5) to 46.5 (range 33.5-53.5) (P < .05). Adaptive capacity increased, with the median Vineland Adaptive Behavior Scales score rising from 53.5 to 60.5. Social communication, language, and daily skills improved markedly within 18 months after transplantation. Conversely, repetitive behaviors and hyperactivity decreased remarkably. Autologous bone marrow mononuclear cell transplantation in combination with behavioral intervention was safe and well tolerated in children with ASD (Trial registration: ClinicalTrials.gov identifier: NCT03225651).
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Transtorno do Espectro Autista , Transplante de Medula Óssea , Leucócitos Mononucleares/transplante , Transtorno do Espectro Autista/terapia , Medula Óssea , Criança , Humanos , VietnãRESUMO
There are eight known genotypes of hepatitis B virus, A-H, and several subgenotypes, with rather well-defined geographic distributions. HBV genotypes were evaluated in 153 serum samples from Hanoi, Vietnam. Of the 87 samples that could be genotyped, genotype B was found in 67 (77%) and genotype C in 19 (22%). All genotype C strains were of subgenotype C1, and the majority of genotype B strains were B4, while a few were B2. The genotype X/C recombinant strain, identified previously in Swedish patients of indigenous Vietnamese origin, was found in one sample. This variant, proposed to be classified as genotype I, has been found recently also by others in Vietnam and Laos. The current study indicates that the genotype X/C recombinant may represent approximately 1% of the HBV strains circulating in Vietnam.
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DNA Viral/genética , Vírus da Hepatite B/classificação , Vírus da Hepatite B/genética , Hepatite B/epidemiologia , Hepatite B/virologia , Recombinação Genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Análise por Conglomerados , DNA Viral/química , Genótipo , Vírus da Hepatite B/isolamento & purificação , Humanos , Lactente , Pessoa de Meia-Idade , Epidemiologia Molecular , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Homologia de Sequência , Vietnã/epidemiologia , Adulto JovemRESUMO
Patients with Rett syndrome (RTT) have severe mental and physical disabilities. The majority of RTT patients carry a heterozygous mutation in methyl-CpG binding protein 2 (MECP2), an X-linked gene encoding an epigenetic factor crucial for normal nerve cell function. No curative therapy for RTT syndrome exists, and cellular mechanisms are incompletely understood. Here, we developed a CRISPR/Cas9-mediated system that targets and corrects the disease relevant regions of the MECP2 exon 4 coding sequence. We achieved homologous recombination (HR) efficiencies of 20% to 30% in human cell lines and iPSCs. Furthermore, we successfully introduced a MECP2R270X mutation into the MECP2 gene in human induced pluripotent stem cells (iPSCs). Consequently, using CRISPR/Cas9, we were able to repair such mutations with high efficiency in human mutant iPSCs. In summary, we provide a new strategy for MECP2 gene targeting that can be potentially translated into gene therapy or for iPSCs-based disease modeling of RTT syndrome.
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BACKGROUND: Recent outbreaks of avian influenza A (H5N1) in poultry throughout Asia have had major economic and health repercussions. Human infections with this virus were identified in Vietnam in January 2004. METHODS: We report the clinical features and preliminary epidemiologic findings among 10 patients with confirmed cases of avian influenza A (H5N1) who presented to hospitals in Ho Chi Minh City and Hanoi, Vietnam, in December 2003 and January 2004. RESULTS: In all 10 cases, the diagnosis of influenza A (H5N1) was confirmed by means of viral culture or reverse transcriptase-polymerase chain reaction with primers specific for H5 and N1. None of the 10 patients (mean age, 13.7 years) had preexisting medical conditions. Nine of them had a clear history of direct contact with poultry (median time before onset of illness, three days). All patients presented with fever (temperature, 38.5 to 40.0 degrees C), respiratory symptoms, and clinically significant lymphopenia (median lymphocyte count, 700 per cubic millimeter). The median platelet count was 75,500 per cubic millimeter. Seven patients had diarrhea. In all patients, there were marked abnormalities on chest radiography. There was no definitive evidence of human-to-human transmission. Eight patients died, one patient has recovered, and one is recovering. CONCLUSIONS: Influenza A (H5N1) infection, characterized by fever, respiratory symptoms, and lymphopenia, carries a high risk of death. Although in all 10 cases the infection appears to have been acquired directly from infected poultry, the potential exists for genetic reassortment with human influenzaviruses and the evolution of human-to-human transmission. Containment of influenza A (H5N1) in poultry throughout Asia is therefore urgently required.