Human beige adipocytes for drug discovery and cell therapy in metabolic diseases.

Human beige adipocytes (BAs) have potential utility for the development of therapeutics to treat diabetes and obesity-associated diseases. Although several reports have described the generation of beige adipocytes in vitro, their potential utility in cell therapy and drug discovery has not been reported. Here, we describe the generation of BAs from human adipose-derived stem/stromal cells (ADSCs) in serum-free medium with efficiencies >90%. Molecular profiling of beige adipocytes shows them to be similar to primary BAs isolated from human tissue. In vitro, beige adipocytes exhibit uncoupled mitochondrial respiration and cAMP-induced lipolytic activity. Following transplantation, BAs increase whole-body energy expenditure and oxygen consumption, while reducing body-weight in recipient mice. Finally, we show the therapeutic utility of BAs in a platform for high-throughput drug screening (HTS). These findings demonstrate the potential utility of BAs as a cell therapeutic and as a tool for the identification of drugs to treat metabolic diseases.

Recommended foscarnet dose is not associated with improved outcomes in cytomegalovirus salvage therapy.

BACKGROUND: Cytomegalovirus (CMV) infection causes significant morbidity and mortality in transplant recipients. Ganciclovir and valganciclovir have proven efficacy but are limited by resistance and toxicity, whereas foscarnet typically retains activity when CMV has become resistant to other antivirals. Foscarnet dosing used in practice may be discordant with what is recommended in product labeling, as the result of an unconventional dosing nomogram or prescriber preference; however, it is unknown how discordant foscarnet dosing affects outcomes. OBJECTIVE: Our purpose was to characterize the relationship between initial foscarnet dosing intensity (relative to product labeling) and key effectiveness and safety endpoints. STUDY DESIGN: This single-center, retrospective study included immunosuppressed adults with CMV viremia who received foscarnet between January 2012-July 2017. Subjects were divided into low dose (LD) and non-low dose (NLD) groups, according to foscarnet dose intensity. The primary endpoint was time-to-CMV eradication. Secondary endpoints included time-to-CMV clearance, acute kidney injury, hematologic toxicity, and mortality. RESULTS: Of 87 subjects, 38 met inclusion. Primary immunosuppression reasons were solid organ (63%) or hematopoietic cell transplant (29%). Seventeen and 21 subjects were in the LD and NLD groups, respectively. Median time-to-CMV eradication was 17 days (LD group) versus 13 days (NLD group), p = 0.823. Median time-to-CMV clearance was also non-significant (p = 0.505). There was no association between initial foscarnet dosing intensity and acute kidney injury, hematologic toxicity, or mortality (24% in both groups). CONCLUSIONS: These findings suggest outcomes may be sensitive to other factors and underscore the need for further studies to improve understanding of foscarnet dosing in immunosuppressed patients.

Applications of kidney organoids derived from human pluripotent stem cells

The establishment of protocols to differentiate kidney organoids from human pluripotent stem cells provides potential applications of kidney organoids in regenerative medicine. Modeling of renal diseases, drug screening, nephrotoxicity testing of compounds, and regenerative therapy are attractive applications. Although much progress still remains to be made in the development of kidney organoids, recent advances in clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated system 9 (Cas9) genome editing and three-dimensional bioprinting technologies have contributed to the application of kidney organoids in clinical fields. In this section, we review recent advances in the applications of kidney organoids to kidney disease modelling, drug screening, nephrotoxicity testing, and regenerative therapy.

Non-cultured Epidermal Cell Suspension Transplantation Using Suction Blisters to Treat Refractory Vitiligo: A Retrospective Study of 20 Cases / 대한피부과학회지

BACKGROUND: As nonsurgical interventions for vitiligo are not always successful, various surgical modalities have been used in patients with refractory vitiligo. Of these, non-cultured epidermal suspension transplantation (NCES) was recently introduced to treat large recipient sites using cells from small donor tissue. OBJECTIVE: We assessed the effectiveness and safety of NCES as a surgical treatment for patients with refractory vitiligo. METHODS: We retrospectively reviewed 20 cases in 17 patients (11 females; median age 25 years) who underwent NCES from July 2015 through March 2018. Suction blisters (20 mm in diameter) were collected from the patient's inner thigh at a donor-to-recipient area ratio of 1:5. After the addition of 5 mL recombinant trypsin solution to the suction blisters, followed by incubation at 37℃ for 60 min, epidermal cells were manually scraped off the blister surface, and epidermal cell suspension was obtained by centrifugation at 1,500 RPM for 5 min. The suspension was applied to the vitiligo regions after epidermal ablation of those regions. Phototherapy resumed 1 month later. Treatment success was defined as ≥75% repigmentation of the surgical site, and all adverse events were noted. RESULTS: Overall, 85.0% of cases (17/20) exhibited treatment success. Adverse events included hyperpigmentation (20%) and surgical site infection (5%), but the treatment was tolerable in all cases. CONCLUSION: NCES is a reliable surgical option for patients with vitiligo refractory to nonsurgical treatment. Large areas of vitiligo can be treated by NCES, and use of this technique should be encouraged in Korea.

Dermoabrasión como alternativa de tratamiento en quemaduras tipo AB en pacientes pediátricos. Experiencia del Servicio de Cirugía Plástica, Unidad de Quemados del Hospital Pediátrico Fernando Bareyro / Dermoabrasion for treatment in pediatric burns

La dermoabrasión en combinación con sulfadiazina de plata y lidocaína, como tratamiento para las quemaduras AB en pacientes pediátricos, presenta ventajas en cuanto a los resultados que ofrece, ya que es un método sencillo y reproducible. Como desventaja presenta que se requieren varias sesiones de tratamiento y en algunos casos, donde se produjo profundización de la lesión, se requirió cobertura con injerto de pie

[Review and analysis of transplant biological research projects funded by National Natural Science Foundation of China].

OBJECTIVE: To study the funding and achievements in the field of organ transplantation support by the National Natural Science Foundation of China (NSFC). METHODS: A search of NSFC database was made by using the key word "transplantation" and excluding "bone marrow transplantation" for the projects funded between 1988 and 2013. SCI indexed publications that marked with NSFC project number were collected by searching each grant number in the database of the Web of Science. RESULTS: Six hundreds fifty-five projects were identified and received about 220 million yuan in grant funding. These funded research projects were distributed among 25 provinces and autonomous regions, however, which were mainly in the developed coastal areas; of them, 43 (6.56%) projects were granted in xenotransplantation and 17 projects (2.60%) were funded in the field of traditional Chinese medicine-related organ transplantation; Transplantation on blood vessels, heart, kidney, liver, lung, small intestine, pancreatic, cornea, trachea, skin, etc. were primarily performed in research. Nine hundreds and sixty-one SCI-indexed publications were achieved. CONCLUSIONS: Magnitude and intensity of NSFC funding, output of SCI publications have been increasing, suggesting that NSFC positively promotes the development of organ transplantation. Although a great progress of transplantation has been made, basic and translational studies should be vigorously strengthened.

[Fecal transplantation the future therapy?]. / Transplantacja stolca terapia przyszlosci?

Intestinal bacteria play an important role in human physiology, taking part in the metabolism, absorption of nutrients and regulation of the immune system. In many illnesses the bacterial imbalance in the digestive tract occurs, and fecal transplantation is one method that allows you to restore the balance. The essence of the described method is to replace the pathogenesis, abnormal bacterial flora with the flora occurring in normal healthy individuals. So far, the main use of the method described in the article is resistant to antibiotics Clostridium difficile infection, which gives you a chance to avoid total colectomy. The article presents an accurate description of the same procedure to prepare the material, the selection of donor, recipient preparation and diseases, such as inflammatory bowel diseases, irritable bowel syndrome, diabetes and obesity, in which this method of treatment is currently practised.

[Underlying dysbiosis may be the cause of some forms of IBS. Patients were free of symptoms after the administration of microbiota]. / Bakomliggande dysbios kan vara orsak till vissa former av IBS - Patienter blev symtomfria efter tillförsel av mikrobiota.

Two cases of post-infectious IBS were successfully treated with transplantation of an anaerobic cultivated human intestinal microbiota. This suggests that a dysbiosis of the intestinal microbiota could be the culprit at least in some cases of IBS. Resetting the gut microbiota might be a possible solution for these patients that otherwise may face a life-long reduction in quality of life. Studies have suggested that conditions as varied as chronic constipation, metabolic syndrome, autoimmunity, asthma, cardiovascular disease and Crohn's disease may be caused by intestinal dysbiosis. If this is the case we would like to suggest a new term: Dysbiotic Bowel Syndrome (DBS).

[A pilot study of treating ulcerative colitis with fecal microbiota transplantation].

OBJECTIVE: To explore the procedure, effectiveness and safety of fecal microbiota transplantation (FMT) in patients with ulcerative colitis (UC). METHODS: Seven patients (6 men and 1 woman, aged 17-66 years) with active UC were treated with FMT through endoscopic duodenal infusion or combined endoscopic duodenal and colonic approaches. The clinical manifestations and laboratory results were recorded before and after FMT respectively. Disease response was evaluated with Mayo scores. Fresh fecal suspension prepared from healthy donors who were strictly screened, was infused into patients' intestinal tracts within 6 hours. RESULTS: The average disease duration of 7 patients with UC was (9.1 ± 8.5) years (range 0.5-24.0 years). One patient underwent FMT for three times and one for twice, while the other five were treated for once. The follow-up time was (98.6 ± 70.8) days (30-210 days). All patients achieved some extent of improvements with the reduction of Mayo scores 7, 4, 6, 5, 6, 9 and 9, respectively. Transient fever, diarrhea and abdominal distension were observed in some patients after FMT, while alleviated spontaneously 2-3 days after the procedure. One patient had high fever and mild ascites caused by secondary infections, which were controlled by the symptomatic treatment and antibiotics. Severe adverse reactions were not found. CONCLUSIONS: FMT is effective to active UC, the short-term side effects and complications are basically acceptable and controllable. The long-term efficacy and risks of FMT need to be verified further.

Adolescentes em hemodiálise: repercussões do adoecimento e tratamento na saúde mental / Teens in hemodialysis: effects of the illness and treatment in mental health

A pesquisa teve como objetivo analisar as repercussões do adoecimento e tratamento na saúde mental dos adolescentes em hemodiálise.Estudo clínico-qualitativo, realizado em uma clínica de diálise do município de Fortaleza/CE de fevereiro a abril de 2013. Foram utilizados como instrumentos de produção de dados a entrevista semiestruturada e a observação não participante. Participaram da pesquisa oito adolescentes com diagnóstico de insuficiência renal crônica, submetidos ao programa de diálise e selecionados por amostragem intencional. Foi utilizada a análise de conteúdo temática de Bardin. Como resultado das entrevistas, tomando o corpus, emergiram duas categorias: Percepção do adolescente renal crônico em hemodiálise sobre a condição vivenciada: sentimentos e expectativas e Repercussões do tratamento hemodiálitico no estilo de vida e saúde mental dos adolescentes. Os resultados evidenciaram que, para os participantes do estudo, a saúde mental é afetada de forma intensa, pois inclui uma luta constante para superar as transformações ocasionadas pela doença e a necessidade de aprender a lidar com sentimentos que provocam desconforto. Conclui-se que o adoecimento e o tratamento hemodialítico repercutem na saúde mental, mas os efeitos negativos podem ser minimizados com a prestação de um cuidado humanizado e integral.

The research aimed at analyzing the impact of the disease and treatment in the mental health of adolescents on hemodialysis. This is a clinical qualitative study carried out in a dialysis clinic of the city of Fortaleza/Ceará from february to april 2013. Data were used as instruments of production to semistructured interviews and non-participant observation. The participants were eight teenagers diagnosed with chronic renal failure undergoing dialysis selected by intentional sampling. The analysis of thematic content of Bardin was used. As a result of theinterviews, taking the corpus, two categories emerged; 1 -Perception of chronic renal hemodialysis teen about the condition experienced: feelings and expectations and 2 -Impact of hemodialysis on lifestyle and mental health of adolescents. The results show that, among the study participants, mental health is affected intensively because in includes a constant struggle to overcome the changes caused by the disease and the need to learn to deal with feelings that cause discomfort. It is conclude that the illness and particularly the hemodialysis affects the mental health, but it can be minimized by the provision of a humanized and comprehensive care.

Effect of electro-acupuncture combined with olfactory ensheathing cell transplantation on spinal cord injury axonal regeneration and direction / 中国骨伤

<p><b>OBJECTIVE</b>To explore the impact and mechanism of electro-acupuncture (EA) on olfactory ensheathing cells (OECs) transplantation of spinal cord injury (SCI) axonal regeneration.</p><p><b>METHODS</b>In the experiment, 72 adult Sprague Dawley male rats weighted (220±20) g underwent contusion and transection method to cause the T9 model of spinal cord injury, were randomly divided into four groups involving model group, EA group,OECs group,and EA+OECs group. 5% fluorescein gold (FG) solution of 0.5 µl was injected into rats' spinal cord at 4 weeks and 8 weeks after SCI, a series of tests were performed including fluorescein gold(FG) retrograde tagging, BBB scores.</p><p><b>RESULTS</b>(1)The BBB scores level among four groups had no differences from the 1st day to the 1st week after the SCI (P>0.05). From the 3rd week after the SCI, the BBB scores level in EA+ OECs group were obviously higher than that of other groups (P<0.05). (2)The result of the fluorescein gold (FG) retrograde tagging showed at 4 weeks and 8 weeks after treatment FG positive nerve fibers were observed in SCI region. In EA+OECs group the number of FG positive nerve fibers was more than other three groups, and the fibers were more regularly arranged than other three groups.</p><p><b>CONCLUSION</b>The combination of electro-acupuncture and OECs transplantation can recover the pathway of nerve conduction and promote nerve fibers regeneration and hind limb function recovery for SCI rat, and can guide the trend of the axonal regeneration.</p>

Review and analysis of transplant biological research projects funded by National Natural Science Foundation of China / 中华外科杂志

<p><b>OBJECTIVE</b>To study the funding and achievements in the field of organ transplantation support by the National Natural Science Foundation of China (NSFC).</p><p><b>METHODS</b>A search of NSFC database was made by using the key word "transplantation" and excluding "bone marrow transplantation" for the projects funded between 1988 and 2013. SCI indexed publications that marked with NSFC project number were collected by searching each grant number in the database of the Web of Science.</p><p><b>RESULTS</b>Six hundreds fifty-five projects were identified and received about 220 million yuan in grant funding. These funded research projects were distributed among 25 provinces and autonomous regions, however, which were mainly in the developed coastal areas; of them, 43 (6.56%) projects were granted in xenotransplantation and 17 projects (2.60%) were funded in the field of traditional Chinese medicine-related organ transplantation; Transplantation on blood vessels, heart, kidney, liver, lung, small intestine, pancreatic, cornea, trachea, skin, etc. were primarily performed in research. Nine hundreds and sixty-one SCI-indexed publications were achieved.</p><p><b>CONCLUSIONS</b>Magnitude and intensity of NSFC funding, output of SCI publications have been increasing, suggesting that NSFC positively promotes the development of organ transplantation. Although a great progress of transplantation has been made, basic and translational studies should be vigorously strengthened.</p>

Application of intense pulsed light depilation in the auricular reconstruction with totally expanded skin / 中华整形外科杂志

<p><b>OBJECTIVE</b>To investigate the application of intense pulsed light (IPL) depilation in the auricular reconstruction with totally expanded skin and its suitable parameter.</p><p><b>METHODS</b>From February 2009 to September 2013, one tissue expander(100 or 150 milliliters) were implanted under the skin of mastoid in 126 patients who suffered from microtia. During the skin expanding, the hair on the expanded skin was depilated by JPL technique. The parameter, operation, interval, the depilation result and the complication were recorded. The autologous rib cartilage frameworks were implanted in the second phase of auricular reconstruction.</p><p><b>RESULTS</b>The energy of IPL was 20 - 35 J/cm2 (mean 25. 3 J/cm2), the width of pulse was 26 - 30 ms ( mean 27. 9 ms), the interval between two operations was 4 weeks. Ninety-six patients were cured(76. 2%, 96/126). The total depilation efficient is 96. 8% (122/126). A fine banding blisters was found in one patient whose depilation areas was marked by black pen. Skin erythema was found in five patients and skin pigmentation was found in 7 patients. There were no skin necrosis and expander exposure in all patients. During 6 - 12 months of follow-up period, ninety-two patients were cured (73.0%, 92/126) and the total depilation efficient is 92. 9% (117/126).</p><p><b>CONCLUSIONS</b>IPL depilation during the skin expanding is feasible and safe with careful procedure. The hairless expanded skin is enough to cover the framework, as well as the post-auricular area. The appearance of reconstructed ear is better without hair.</p>

Faecal microbiota transplantation.

The use of faeces for the treatment of gastrointestinal diseases was described in 4th century Chinese medicine for the treatment of severe diarrhoea.1 More recently there has been renewed interest in this unconventional biological therapy, particularly for the treatment of recurrent Clostridium difficile infection (CDI) and to a lesser extent inflammatory bowel diseases (IBD). Faecal microbiota transplantation† (FMT) involves the introduction of enteric bacteria from the faeces of healthy donors in order to restore a healthy balance of bacteria in the gut.2 In March 2014, the National Institute for Health and Care Excellence (NICE) issued guidance on the use of FMT for the treatment of recurrent CDI that has failed to respond to antibiotics and other treatments.2 Here we review the use of FMT in CDI and IBD.

[Experience with fecal transplantation in the treatment of Clostridium difficile infection]. / Clostridium difficile-fertozések széklettranszplantációval való kezelése során nyert tapasztalataink.

INTRODUCTION: During the past years a dramatic change has been observed in the epidemiology of Clostridium difficile infections. AIM: The aim of the authors was to investigate the possibility of the fecal microbiota transplantation and study differences, if any, in the success rate of the two different upper gastrointestinal tract method. METHOD: 100 ml of fecal microbiota solution was instilled via a nasoduodenal tube in 15 cases and a nasogastric tube in 15 cases. The authors defined the primary cure rate as the percentage of cases in which the symptoms disappeared without recurrence within 6 weeks after the first fecal microbiota transplantation, while secondary cure rate was calculated as the percentage of cases in which the symptoms resolved after the second fecal microbiota transplantation. RESULTS: It was found that fecal microbiota transplantation applied via the nasoduodenal tube resulted in a 100% primary cure rate. With the use of the nasogastric tube, the primary and secondary cure rate were 80% and 93.3%, respectively. Fecal microbiota transplantation via the upper gastrointestinal tract was found to have an overall primary cure rate of 90.0% and a secondary cure rate of 96.7%. CONCLUSIONS: Fecal microbiota transplantation proved to be very effective, particularly in recurrent infections and cases where conventional treatment failed.

[Fecal microbiota transplantation: first case report in Chile and review]. / Trasplante de microbiota fecal: primer caso reportado en Chile y revisión de la literatura.

Clostridium difficile (CD) infection is increasing in frequency and severity in in-hospital and outpatient clinical settings, with a recurrence that can reach 30% after first episode. The recurrences are usually treated with longer courses of metronidazole or vancomycin. Other treatments have been used, such as probiotics, fidaxomicin, rifaximin, immunoglobulins and monoclonal antibodies against toxins A and B. Fecal microbiota transplantation (FMT) has emerged as a promising strategy in this group of patients, with effectiveness greater than 90%. We present the first case reported in Chile of this therapeutic strategy in a patient with Crohn's disease and recurrent CD infection who presented after the fecal transplantation an Escherichia coli bacteremia, suggesting the need for caution in the use of this strategy. 10 months after the FMT the patient presented a new episode of E. coli bacteremia and two episodes of diarrhea due to CD infection, treated both of them with vancomycin with good clinical response.

Trasplante de microbiota fecal: primer caso reportado en Chile y revisión de la literatura / Fecal microbiota transplantation: first case report in Chile and review

Clostridium difficile (CD) infection is increasing in frequency and severity in in-hospital and outpatient clinical settings, with a recurrence that can reach 30% after first episode. The recurrences are usually treated with longer courses of metronidazole or vancomycin. Other treatments have been used, such as probiotics, fidaxomicin, rifaximin, immunoglobulins and monoclonal antibodies against toxins A and B. Fecal microbiota transplantation (FMT) has emerged as a promising strategy in this group of patients, with effectiveness greater than 90%. We present the first case reported in Chile of this therapeutic strategy in a patient with Crohn's disease and recurrent CD infection who presented after the fecal transplantation an Escherichia coli bacteremia, suggesting the need for caution in the use of this strategy. 10 months after the FMT the patient presented a new episode of E. coli bacteremia and two episodes of diarrhea due to CD infection, treated both of them with vancomycin with good clinical response.

La infección por Clostridium difficile (CD) está aumentando en frecuencia y gravedad tanto a nivel intrahospitalario como ambulatorio, con una recurrencia que puede alcanzar hasta 30% después de un primer episodio. Los cuadros recurrentes son generalmente tratados con cursos prolongados de metronidazol y/o vancomicina. Otras terapias han sido sugeridas como el uso de probióticos, fidaxomicina, rifaximina, inmunoglobulina y anticuerpos monoclonales para toxina A y B. El trasplante de microbiota fecal (TMF) ha emergido como una estrategia promisoria en este grupo de pacientes con una efectividad mayor a 90%. Presentamos el primer caso reportado en Chile de esta estrategia terapéutica en un paciente con enfermedad de Crohn y CD recurrente, quien presentó una bacteriemia por Escherichia coli post-TMF, sugiriendo la necesidad de tener precaución con el uso de esta estrategia. El paciente presentó a los 10 meses post-TMF un nuevo episodio de bacteriemia por E. coli y dos episodios de diarrea por CD siendo tratados ambos cuadros con vancomicina con buena respuesta clínica.