Consenso Argentino sobre Diagnóstico y Tratamiento de la Enfermedad de Niemann-Pick tipo C / Argentinean Consensus on the Diagnosis and Treatment of Niemann-Pick Disease type C

Resumen La enfermedad de Niemann-Pick tipo C (NPC) es un trastorno del metabolismo lisosomal que se debe a la presencia de variantes patogénicas bialélicas en los genes NPC1 o NPC2. El depósito intracelular de lípidos, especialmente colesterol no esterificado, provoca daño oxidativo en diversos tejidos, especialmente neuronas, bazo e hígado. Esto, a su vez, induce la aparición de un conjunto de síntomas neurológicos/psiquiátricos y viscerales, con una amplia variabilidad de edad de apa rición, desde formas prenatales/neonatales hasta otras de aparición en la vida adulta. En los últimos años ha habido avances considerables en la comprensión sobre esta enfermedad y su manejo. En el presente consenso un grupo de expertos argentinos abordan los enfoques actuales de diagnóstico, seguimiento y tratamiento de NPC, incluyendo el uso de miglustat como única terapia específica aprobada en la actualidad.

Abstract Niemann-Pick type C (NPC) is a disorder of the lyso somal metabolism due to biallelic pathogenic variants in NPC1 or NPC2. Intracellular deposit of lipids, mainly unesterified cholesterol, gives rise to oxidative damage in several tissues, mainly neurons, spleen and liver. This, in turn, is associated with a myriad of neurologi cal/psychiatric and visceral symptoms, with wide vari ability in age of presentation, from prenatal/neonatal to adult-onset forms of the disease. The last few years have seen considerable progress in understanding this disease and its management. In this consensus, current approaches to the diagnosis, follow-up and treatment of NPC (including the use of miglustat, the only specific drug approved at the time) are discussed by an Argentin ian panel of experts.

A non-toxic recombinant protein rSUMO-CPBm4 as a potential vaccine candidate against Clostridium perfringens type C beta enterotoxemia

@#Beta toxin (CPB) is a lethal toxin and plays a key role in enterotoxemia of ruminants caused by Clostridium perfringens type C strain. The existing vaccines based on crude CPB need time-consuming detoxification and difficult quality control steps. In this study, we synthesized the rCPBm4 of C. perfringens type C strain and small ubiquitin-like modifier (SUMO)-tag CPBm4 (rSUMO-CPBm4) by introducing four amino acid substitutions: R212E, Y266A, L268G, and W275A. Compared with rCPBm4, rSUMO-CPBm4 was expressed with higher solubility in Escherichia coli BL21 (DE3). Neither rCPBm4 nor rSUMO-CPBm4 was lethal to mice. Although rCPBm4 and rSUMO-CPBm4 were reactogenic with polyclonal antibodies against crude CPB, rabbits vaccinated with rSUMO-CPBm4 developed significant levels of toxin-neutralizing antibody (TNA) titers that conferred protection against crude toxin challenge. These data suggest that genetically detoxified rSUMO-CPBm4 is a promising subunit vaccine candidate for C. perfringens type C beta enterotoxemia.

Berberine Inhibits Atherosclerosis by Regulating Lipophagy Via Targeting Wnt5a/NPC1 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the regulatory effect and molecular mechanism of berberine （BBR） on lipophagy in the prevention and treatment of atherosclerotic （AS） lesions in mice. MethodFifty apolipoprotein E-knockout （ApoE-/-） mice were randomly divided into an AS model group， an atorvastatin group （5 mg·kg-1）， and low-， medium-， and high-dose BBR groups （2.5， 5， 10 mg·kg-1）. Ten C57BL/6J mice were assigned to the control group. After 12 weeks， hematoxylin-eosin （HE） and oil red O staining were performed to assess the histopathological changes of AS plaques in the aorta. Biochemical analysis was used to measure serum lipid levels， and enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of inflammatory cytokines interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α）， oxidative stress marker reactive oxygen species （ROS）， and serum lipophagy marker Beclin1 and microtubule-associated protein 1 light chain 3 Ⅱ （LC3Ⅱ）. The xanthine oxidase method was used to measure serum superoxide dismutase （SOD） activity. Immunohistochemistry （IHC） was used to detect the distribution of wingless-type MMTV integration site family member 5a （Wnt5a） and Nieman Pick type C1 （NPC1） in the aorta， and Western blot was used to determine the protein expression of Wnt5a and NPC1 in the aorta. ResultCompared with the control group， the AS model group showed significant AS plaque formation， significantly elevated levels of serum total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， IL-6， TNF-α， and ROS， aortic Wnt5a distribution and protein expression （P<0.01）， and significantly reduced levels of serum high-density lipoprotein cholesterol （HDL-C）， SOD， Beclin1， LC3Ⅱ， and aortic NPC1 distribution and protein expression （P<0.01）. Compared with the AS model group， the atorvastatin group， and high- and medium-dose BBR groups showed a significant reduction in AS plaque area （P<0.05， P<0.01）， significantly decreased levels of serum TC， TG， LDL-C， IL-6， TNF-α， ROS， and aortic Wnt5a distribution and protein expression （P<0.05， P<0.01）， and significantly increased levels of serum HDL-C， SOD， Beclin1， LC3Ⅱ， and aortic NPC1 distribution and protein expression （P<0.05， P<0.01）. There was no statistically significant difference in the above indicators between the atorvastatin group and the medium-dose BBR group. ConclusionBBR can competitively bind to Wnt5a to activate NPC1 expression， upregulate lipophagy levels， reduce blood lipids， and inhibit the release of inflammatory mediators and oxidative stress damage， thereby exerting a preventive and therapeutic effect on AS.

Comparison of filling ratio, alignment, and stability between ABG Ⅱ short-stem and Corail long-stem in total hip arthroplasty for Dorr type C femur / 中国修复重建外科杂志

OBJECTIVE@#Using the mono-energy reconstruction images and X-ray films to investigate whether the ABG Ⅱ short-stem could improve the filling ratio, stability, and alignment in the Dorr type C femur, compared with the Corail long-stem.@*METHODS@#Among patients who were with Dorr type C femurs and treated with total hip arthroplasty between January 2006 and March 2012, 20 patients with a Corail long-stem (Corail group) and 20 patients with an ABG Ⅱ short-stem (ABG Ⅱ group) were randomly selected. The differences in gender, age, body mass index, and preoperative diagnoses between the two groups were not significant ( P>0.05). The ABG Ⅱ group was with a mean follow-up of 142 months (range, 102-156 months), and the Corail group was with a mean follow-up of 107 months (range, 91-127 months). There was no significant difference in the Harris score and subjective satisfaction score between the two groups at last follow-up ( P>0.05). At last follow-up, dual-energy CT scans with mono-energy image reconstruction were used to calculate the prosthetic filling ratio and to measure the alignment of the prosthesis in the coronal and sagittal positions. Stability assessment was performed based on X-ray films, and the subsidence distance was measured using EBRA-FCA software.@*RESULTS@#X-ray film observation showed that the prostheses in the two groups were stable and no signs of loosening was found. The incidence of pedestal sign was significantly lower in the ABGⅡ group than in the Corail group ( P<0.05), and the incidence of heterotopic ossification was significantly higher in the ABGⅡ group than in the Corail group ( P<0.05). The subsidence distance of femoral stem in ABG Ⅱ group was significantly greater than that in Corail group ( P<0.05), and the subsidence speed of femoral stem in ABG Ⅱ group was also greater than that in Corail group, but the difference was not significant ( P>0.05). The overall prosthesis filling ratio was significantly higher in the ABG Ⅱ group than in the Corail group ( P<0.05), while the coronal filling ratio at the lesser trochanter, 2 cm below the lesser trochanter, and 7 cm below the lesser trochanter were not significant ( P>0.05). The results of prosthesis alignment showed that there was no significant difference in the sagittal alignment error value and the incidence of coronal and sagittal alignment error >3° between the two groups ( P>0.05), while the coronal alignment error value in the ABG Ⅱ group was significantly greater than that in the Corail group ( P<0.05).@*CONCLUSION@#Although the ABG Ⅱ short-stem avoids the distal-proximal mismatch of the Corail long-stem in the Dorr type C femur and thus achieves a higher filling ratio, it does not appear to achieve better alignment or stability.

A family of Niemann-Pick disease type C caused by compound heterozygous mutations in NPC1 gene / 中华神经科杂志

Objective:To report the clinical and genetic characteristics of a family with Niemann-Pick disease type C caused by novel compound heterozygous mutations in the NPC1 gene to improve the clinicians′ recognition of the disease. Methods:Two patients from the family with non-consanguineous marriages admitted to the Department of Neurology of the First Affiliated Hospital of Kunming Medical University in 2020 were examined in detail. Peripheral blood DNA was extracted, and whole exome sequencing was performed on the patients, combined with Sanger sequencing for verification. The mutation and protein function predictor softwares were applied to analyze the mutation sites.Results:The inheritance was autosomal recessive in this family. The onset age of the proband was 9 years, and the main clinical manifestations were dysarthria, dysphagia, cognitive impairment, ataxia, bilateral pyramidal tract impairment, vertical supranuclear gaze palsy and splenomegaly. The clinical phenotype of the proband′s younger brother was similar to that of the proband, but it was more severe than that of the proband. The younger brother of the proband had an earlier age of onset and severe psychomotor retardation. Whole exome sequencing showed that both brothers carried 2 rare variants of NPC1 gene:1 pathogenic, stop gain at c.352_353del, p.Gln119ValfsTer8, and a missense change, c.593A>G, p.Asn198Ser, of suspected pathogenic. Sanger sequencing confirmed that compound heterozygous mutations were derived from the proband′s parents. According to the American College of Medical Genetics and Genomics guidelines, the above variants were rated as pathogenic and suspected pathogenic, respectively. And the c.593A>G, p.Asn198Ser mutation found in this family was a novel one which had not been reported yet. The proband had delayed diagnosis for 7 years from the onset of symptoms. After taking megastat for 1 year, the symptoms of dysphagia, ataxia and vertical eye movement disorder were significantly improved. Conclusions:The clinical phenotype of the pedigree was consistent with the clinical phenotype of Niemann-Pick disease type C. Compound heterozygous mutations of NPC1 gene (c.352_353del; c.593A>G) were found to be the genetic cause of the family.

Molecular and functional study of pediatric patients with Niemann-Pick C in Argentina / Estudio molecular y funcional de pacientes pediátricos con Niemann-Pick C en Argentina

Abstract Niemann-Pick type C (NP-C) is a rare, autosomal recessive disorder. At least 95% of all the cases with this disease are due to mutations in the NPC1 gene. The clinical signs and symptoms of NP-C are classified into visceral, neurological and psychiatric. Our aim is to report the clinical findings, molecular results and filipin staining of 4 patients. The age of onset, expressed as median and range, was 0.2 (0.08-4.0) years and the age of diagnosis was 4.0 (2.5-8.9) years. Neurological and/or visceral manifestations were presented in our patients. Foamy cells in bone marrow biopsy were found in two patients. Through a molecular analysis of NPC1 gene, one non-reported (novel) and 4 previously described mutations were found. The filipin staining showed a positive pattern in all the patients. The diagnostic confirmation of these pediatric patients means a contribution to the casuistry of this disease in Argentina.

Resumen Niemann-Pick tipo C (NP-C) es una enfermedad poco frecuente, con un patrón de herencia au tosómico recesivo. Al menos el 95% de los casos se producen por mutaciones en el gen NPC1. Los signos y síntomas clínicos de NP-C se clasifican en viscerales, neurológicos y psiquiátricos. En este trabajo presentamos los hallazgos clínicos, los resultados moleculares y la tinción con filipina de 4 pacientes con NP-C. La edad de presentación de los primeros síntomas, expresada como mediana y rango, fue de 0.2 años (0.08-4.0) años y la edad del diagnóstico fue 4.0 (2.5-8.9) años. Los pacientes presentaron manifestaciones neurológicas y / o vis cerales. Se encontraron células espumosas en la biopsia de médula ósea en 2 pacientes. El análisis molecular del gen NPC1 encontró 1 variante nueva y 4 previamente publicadas. La tinción de filipina mostró un patrón positivo en todos los pacientes. La confirmación diagnóstica de este grupo de pacientes pediátricos significa un aporte a la casuística de esta enfermedad en Argentina.

Bilateral triceps tendon approach is flexible and efficient in the treatment of type C distal humerus fractures / 中华创伤杂志(英文版)

PURPOSE@#The purpose of this study was to assess and compare elbow range of motion, triceps extension strength and functional results of type C (AO/OTA) distal humerus fractures treated with bilateral triceps tendon (BTT) approach and olecranon osteotomy (OO). At the same time, we are also trying to know whether BTT approach can provide sufficient vision for comminuted intra-articular fractures of the distal humerus, and whether it is convenient to convert to the treatment to total elbow arthroplasty (TEA) or OO.@*METHODS@#Patients treated with OO and BTT approaches for type C distal humerus fractures between July 2014 and December 2017 were retrospectively reviewed. Inclusion criteria include: (1) patients' age were more than 18 years old, (2) follow-up was no less than 6 months, and (3) patients were diagnosed with type C fractures (based on the AO/OTA classification). Exclusion criteria include: (1) open fractures (Gustillo type 2 or type 3), (2) treated by other approaches, and (3) presented with combined injuries of ipsilateral upper extremities, such as ulnar nerve. Elbow range of motion and triceps extension strength testing were completely valuated, when the fractures had healed. Assessment of functional results using the Mayo elbow performance score and complications were conducted in final follow-up. The data were compared using the two tailed Student's t-test. All data were presented as mean ± standard deviation.@*RESULTS@#Eighty-six patients of type C distal humerus fractures, treated by OO and BTT approach were retrospectively reviewed between July 2014 and December 2017. Fifty-five distal humerus fractures (23 males and 32 females, mean age 52.7 years) treated by BTT approach or OO were included in this study. There were 10 fractures of type C1, 16 type C2 and 29 type C3 according to the AO/OTA classification. Patients were divided into two surgical approach groups chosen by the operators: BTT group (28 patients) and OO group (27 patients). And the mean follow-up time of all patients was 15.6 months (range, 6-36 months). Three cases in BTT group were converted to TEA, and one converted to OO. Only one case in BTT group presented poor articular reduction with a step more than 2 mm. There were not significantly different in functional outcomes according to the Mayo elbow performance score, operation time and extension flexion motion are values between BTT group and OO group (p > 0.05). Complications and reoperation rate were also similar in the two groups. Triceps manual muscle testing were no significant difference in the two groups, even subdivided in elder patients (aged >60 years old).@*CONCLUSION@#BTT is a safe approach to achieve similar functional result comparing with OO. BTT were not suitable for every case with severe comminuted pattern, but it avoids the potential complications related to OO, and has no complications concerning with triceps tendon. It is convenient for open reduction internal fixation and flexible to be converted to OO, as well as available to be converted to TEA in elder patients.

Type C botulism in dogs from rural properties located in Goiânia, Brazil

Botulism is a disease usually fatal, caused by the ingestion of neurotoxins produced by Clostridium botulinum. In dogs, intoxication is caused by the ingestion of botulinum toxin type C, and animals often recover spontaneously. The present study describes the occurrence of type C botulism in two dogs domiciled on neighboring rural properties in the municipality of Goiânia, state of Goiás, Brazil, probably associated with ingestion of decomposing bovine carcass. Upon clinical evaluation, the dogs were alert in the lateral decubitus position with ascending flaccid paralysis, absence of eyelid reflexes, and reduced muscle tone. Due to their worsening clinical symptoms, the animals died within 12 h and 3 days after supportive treatment. Botulinum toxin type C was identified, in the serum and feces of both dogs, by seroneutralization in mice with homologous monovalent antitoxin. The results of the high-throughput gene sequencing showed that the abundance of C. botulinum in the fecal microbiota of one of the affected dogs was low (0.53%). In this way, the present study highlights the need of sanitary practices related to the appropriate collection and disposal of bovine carcasses in rural areas since they represent a risk factor for the occurrence of botulism in dogs domiciled on rural properties.

Advance in Niemann-Pick disease type C / 国际儿科学杂志

Niemann-Pick disease type C is a lipid storage disorder associated with impaired intracellular cholesterol trafficking, caused by mutations of either NPC1 or NPC2 genes.According to the age at onset of symptoms, it is divided into 5 categories, including neonatal, early-infantile, late-infantile, juvenile and adult type.There are differences in clinical manifestations and prognoses among each category.The characteristic clinical manifestations are hepatosplenomegaly, lung infiltration, vertical supranuclear gaze palsy and gelastic cataplexy.The definite diagnosis requires demonstration of unesterified cholesterol accumulated in fibroblasts cultured from skin biopsies with filipin staining and(or) of pathogenic mutation of NPC1/NPC2 genes.There is no effective treatment for this disease yet, therefore the overall prognosis is still poor.Miglustat can delay onset of the neurological symptoms, and prolong survival of partial patients.

Outcomes of Advanced Oncological Laparoscopic Procedures in a Tertiary Care Center

Introduction: Advanced laparoscopic procedures are performed in oncology for almost all visceral sites. We present theoncological and functional outcomes of series of patients who underwent advanced laparoscopic oncological procedures inour tertiary care center.Materials and Methods: We analyzed 34 consecutive patients who underwent advanced laparoscopic oncological proceduresby the same surgeon in the department of surgical oncology during the period of 2015–2019. Five patients underwentlaparoscopic type C1 radical hysterectomy. Laparoscopic abdominoperineal resection was done for six patients, laparoscopicstaging for carcinoma endometrium for seven patients, thoracoscopic esophagectomy for five patients, laparoscopic-assisteddistal gastrectomy for two patients, and laparoscopic staging for ovarian cancer for four patients. Laparoscopic right radicalnephrectomy and laparoscopic right hemicolectomy were done for one patient each.Results: Out of the five patients who underwent laparoscopic Type C1 radical hysterectomy, one patient had residual IB1disease. There was no bladder morbidity and all patients are alive without disease. Two patients who underwent laparoscopicabdominoperineal resection and one patient after thoracoscopic esophagectomy developed disease recurrence. None of thepatients who underwent other procedures had major morbidity or disease recurrence.Conclusion: Advanced laparoscopic procedures are feasible in oncology with minimal morbidity and good oncological outcome.The nodal yield and oncological outcome improve with increasing experience of the surgeon in minimally invasive surgicaloncology.

Novel compound heterozygous mutation in NPC1 gene cause Niemann–Pick disease type C with juvenile onset

Niemann–Pick disease type C (NPC) is a progressive lysosomal storage disorder caused by mutations in the NPC1 (in 95% of cases) or NPC2 (in *5% of cases) genes, inherited in an autosomal recessive manner. We report the case of a 38-year-old woman with learning disorder from her first year of schooling, and could notice slow progressed cognitive impairment, social withdrawal, apathy, handwriting alterations, deterioration of language skills and dysphagia. Brain magnetic resonance imaging showed severe cerebellar atrophy, hypoplasia of the corpus callosum, asymmetric lateral ventricular enlargement, and severe enlargement of frontal and parietal subarachnoid spaces. Next generation sequencing for NPC genes (NPC1 and NPC2) detected compound heterozygous mutations in NPC1 gene, including c.1553G [A (p.Arg518Gln), paternally inherited, and c.1270C [ T (p.Pro424Ser) maternally inherited. The first mutation has been already described in literature and correlated to NPC, while the second mutation is still unknown. Moreover, filipin test and quantification of plasma oxysterols confirmed NPC diagnosis. We can suggest the missense mutation c.1270C [ T (p.Pro424Ser) as a new causative mutation of NPC

Enfermedad de Niemann-Pick en una escolar / Niemann-Pick Disease in a scholar girl

Introducción: La enfermedad de Niemann-Pick tipo C es una enfermedad poco frecuente, autosómica recesiva, caracterizada por el depósito de lípidos a nivel lisosomal, que, a pesar de ser tratable, es mortal en todos los casos y representa una importante carga para los pacientes y sus familias. Objetivo: Contribuir al conocimiento de esta rara enfermedad neurovisceral progresiva de curso fatal. Presentación del caso: Se trata de una niña de 7 años de edad, que a los 2 años asistió a consulta por trastornos de la marcha, con deterioro progresivo de esta, así como del lenguaje y el comienzo de crisis epilépticas. Evolutivamente presentó cataplejías gelásticas, paresia de la mirada vertical y esplenomegalia. Estos elementos clínicos evolutivos fueron lo suficientemente distintivos para orientar la sospecha clínica y las investigaciones necesarias para llegar al diagnóstico definitivo de la enfermedad. Con la confirmación de que se trataba de la enfermedad de Niemann-Pick tipo C, se comenzó tratamiento con miglustad a dosis de 100 mg dos veces al día. Conclusiones: El deterioro neurológico progresivo, la cataplejía gelástica, la paresia de la mirada vertical y la esplenomegalia, unido a los resultados del medulograma y el estudio genético permitieron el diagnóstico de esta entidad(AU)

Introduction: Niemann-Pick type C disease is a non-frequent, recessive autosomal one, which is characterized by lipids deposit in the lysosomal level. Although this disease is treatable, it is fatal in all the cases and it represents a important burden to patients and their families. Objective: To contribute to the knowledge on this rare, progressive neurovisceral disease with fatal evolution. Case presentation: Seven- years- old girl, whom at two years old attended to a consultation for walk disorders presenting a progressive worsening of it, as well of the speech, and also presented an onset of epileptic crisis. In the evolution she presented gelastic cataplexy, vertical look´s paresia and splenomegaly. These clinical evolutive elements were sufficiently distinctive to indicate the clinical suspicion and the necessary research to reach its definitive diagnostic. With the confirmation of Niemann-Pick type C disease, miglustad was used as treatment with a dose of 100 mg twice in the day. Conclusions: Progressive neurological worsening, gelastic cataplexy, vertical look´s paresia and splenomegaly joined with the results of a medulogram and the genetic study permitted this disease to be identified(AU)

Niemann-Pick Disease Type C Misdiagnosed as Cerebral Palsy: A Case Report

Niemann-Pick disease type C (NP-C) is a rare autosomal recessive neurovisceral lysosomal lipid storage disorder. The clinical manifestations of the disorder are variable. This report describes the case of a 27-month-old girl with NP-C whose condition had been misdiagnosed as spastic cerebral palsy (CP). She had spasticity, particularly at both ankles, and gait disturbance. Magnetic resonance imaging of the brain revealed findings suspicious of sequelae from a previous insult, such as periventricular leukomalacia, leading to the diagnosis of CP. However, she had a history of hepatosplenomegaly when she was a fetus and her motor development had deteriorated, with symptoms of vertical supranuclear gaze palsy, cataplexy, and ataxia developing gradually. Therefore, NP-C was considered and confirmed with a genetic study, which showed mutation of the NPC1 gene. Thus, if a child with CP-like symptoms presents with a deteriorating course and NP-C-specific symptoms, NP-C should be cautiously considered.

Identification of phospholipase C β downstream effect on transient receptor potential canonical 1/4, transient receptor potential canonical 1/5 channels

Gα(q)-coupled receptor stimulation was implied in the activation process of transient receptor potential canonical (TRPC)1/4 and TRPC1/5 heterotetrameric channels. The inactivation occurs due to phosphatidylinositol 4,5-biphosphate (PI(4,5)P₂) depletion. When PI(4,5)P₂ depletion was induced by muscarinic stimulation or inositol polyphosphate 5-phosphatase (Inp54p), however, the inactivation by muscarinic stimulation was greater compared to that by Inp54p. The aim of this study was to investigate the complete inactivation mechanism of the heteromeric channels upon Gα(q)-phospholipase C β (Gα(q)-PLCβ) activation. We evaluated the activity of heteromeric channels with electrophysiological recording in HEK293 cells expressing TRPC channels. TRPC1/4 and TRPC1/5 heteromers undergo further inhibition in PLCβ activation and calcium/protein kinase C (PKC) signaling. Nevertheless, the key factors differ. For TRPC1/4, the inactivation process was facilitated by Ca²⁺ release from the endoplasmic reticulum, and for TRPC1/5, activation of PKC was concerned mostly. We conclude that the subsequent increase in cytoplasmic Ca²⁺ due to Ca²⁺ release from the endoplasmic reticulum and activation of PKC resulted in a second phase of channel inhibition following PI(4,5)P₂ depletion.

Modified staging strategy in treatment of type C3 Pilon fractures / 中国修复重建外科杂志

Objective: To investigate the safety, feasibility, and effectiveness of modified staging strategy in treatment of type C3 Pilon fractures. Methods: The clinical data of 23 patients with type C3 Pilon fractures treated with modified staging strategy between January 2012 and January 2018 was retrospectively analyzed. There were 14 males and 9 females with an average age of 47.9 years (range, 22-61 years). Twenty-three cases were high-energy injuries, including 11 cases of traffic accidents and 12 cases of falling from height. One case was an open fracture of Gustilo type ⅢA with no obvious sign of infection on the wound after early treatment. The remaining patients were closed fractures. The time from injury to admission was 3-40 hours with an average of 16.4 hours. The preoperative pain visual analogue scale (VAS) score was 7.22±1.17 and American Orthopaedic Foot and Ankle Society (AOFAS) score was 0. The flexion and plantar flexion activities of ankle joint were (1.13±0.26) and (4.79±0.93)°, respectively. Twenty-two patients had a tibiofibular fracture. In the first-stage operation, the posterior approach was used to reduce the posterior column fracture and the external stent was temporarily assisted. After the soft tissue crisis was removed, the final fracture reduction and internal fixation was performed through the anterior approach in the second-stage operation. Results: All 23 patients were followed up 12-84 months with an average of 26.6 months. The waiting time before the first-stage operation was 4-47 hours with an average of 23.4 hours. The interval between the two stage operations was 6-11 days with an average of 7.9 days. The first-stage operation time was 60-90 minutes with an average of 67.8 minutes; the second-stage operation time was 110-160 minutes with an average of 124.1 minutes. The hospital stay was 15-28 days with an average of 23.5 days. One patient (4.35%) had a tourniquet paralysis symptom after the second-stage operation, and two patients (8.7%) had delayed anterior incision healing. The other patients had incision healing without early complications. The radiographic review showed that the quality of articular surface reduction was excellent in 19 cases, good in 2 cases, and poor in 2 cases, with an excellent and good rate of 91.3%. At last follow-up, the fractures healed with no bone nonunion and malunion; the different degrees of osteoarthritis occurred in 7 cases. At last follow-up, the VAS score was 0.89 ±0.88 and the AOFAS score was 81.3±7.8. The flexion and plantar flexion activities of ankle joint were (10.23±5.05) and (20.97±3.92)°, respectively, and the differences between pre- and post-operation were significant ( P<0.05). Conclusion: The midified staging strategy can not only provide a template for articular surface reduction for the second-stage anterior surgery, but also improve the quality of the reduction. It can also reduce the interval between the two operations and the operation time of the second-stage operation through the first-stage posterior fascial decompression, and can obtain satisfactory effectiveness.

A pele que somos e a pele que sentimos: Pele - símbolo - consciência / The skin we are, the skin we feel: Skin - symbol - consciousness / La piel que somos y la piel que sentimos: Piel - símbolo - conciencia

O sistema somatosensorial humano funciona de forma dinâmica. Nossos órgãos recebem e produzem estímulos que são convertidos em informação biológica, necessária para a formação, maturação e funcionamento global do nosso corpo, mente e espírito. O "sentir-se bem, sentir-se com saúde" é uma consequência de vários fenômenos biológicos que envolvem o sistema nervoso central. Neste contexto, serão abordados os papéis da pele, do tato e do toque no desenvolvimento e estruturação da consciência e do que se chama "pele simbólica" ou "pele psíquica".

The human somatosensory system works in a dynamic way. Our organs receive and produce stimuli that will be converted into biological information, which are necessary for formation, maturation and the overall functioning of the body, mind, and spirit. The "wellbeing sensation" is a result of several biological phenomena that involve the central nervous system. In this context, the role of skin, tact and touch in the development and structuring of our consciousness will be discussed. The concepts of "symbolic skin" and "psychic skin" will be explored.

El sistema somatosensorial humano funciona de forma dinámica. Nuestros órganos reciben y producen estímulos que se convierten en información biológica, necesaria para la formación, maduración y funcionamiento global de nuestro cuerpo, mente y espíritu. El "sentirse bien, sentirse con salud" es una consecuencia de varios fenómenos biológicos que involucran el sistema nervioso central. En este contexto, se abordarán el papel de la piel, del tacto y del toque en el desarrollo y estructuración de la conciencia y de lo que se llama "piel simbólica" o "piel psíquica".

Type C feruloyl esterase from Aspergillus ochraceus: a butanol specific biocatalyst for the synthesis of hydroxycinnamates in a ternary solvent system

Background: Aspergillus ochraceus was isolated from coffee pulp and selected as an interesting hydroxycinnamoyl esterase strain producer, using an activity microplate high-throughput screening method. In this work, we purified and characterized a new type C A. ochraceus feruloyl esterase (AocFaeC), which synthesized specifically butyl hydroxycinnamates in a ternary solvent system. Results: AocFaeC was produced by solid state fermentation, reaching its maximal activity (1.1 U/g) after 48 h of culture. After purification, the monomeric protein (34 kDa) showed a specific activity of 57.9 U/mg towards methyl ferulate. AocFaeC biochemical characterization confirmed its identity as a type C feruloyl esterase and suggested the presence of a catalytic serine in the active site. Its maximum hydrolytic activity was achieved at 40°C and pH 6.5 and increased by 109 and 77% with Ca2+ and Mg2+, but decreased by 90 and 45% with Hg2+ and Cu2+, respectively. The initial butyl ferulate synthesis rate increased from 0.8 to 23.7 nmol/min after transesterification condition improvement, using an isooctane:butanol:water ternary solvent system, surprisingly the synthesis activity using other alcohols was negligible. At these conditions, the synthesis specific activities for butyl p-coumarate, sinapinate, ferulate, and caffeate were 87.3, 97.6, 168.2, and 234 U/µmol, respectively. Remarkably, AocFaeC showed 5 folds higher butyl caffeate synthesis rate compared to type B Aspergillus niger feruloyl esterase, a well-known enzyme for its elevated activity towards caffeic acid esters. Conclusions: Type C feruloyl esterase from A. ochraceus is a butanol specific biocatalyst for the synthesis of hydroxycinnamates in a ternary solvent system

Analysis on clinical effect of volar side locking compression titanium plate and external fixation trestle for treating unstable type C distal radius fracture / 重庆医学

Objective To comparatively analyze the clinical effects of volar locking compression titanium plate and external fixation trestle for treating unstable type C distal radius fracture.Methods The clinical data of 78 patients with unstable type C distal radius fracture treated in this hospital from March 2014 to February 2016 were analyzed retrospectively.The patients were di-vided into the volar locking plate group and external fixattio trestle group according to different treatment methods,39 cases in each group.The clinical efficacies of different treatment methods were observed.Results The postoperative bleeding volume,operation time,hospitalization time and fracture healing time in the external fixation group were less than those in the volar locking plate frac-ture group(P<0.05).The palmar tilt angle,ulnar inclination angle and radial height on postoperative 3 d,6 weeks and 24 mopnths in the volar locking plate group were significantly better than those in the external fixation group(P<0.05).The last follow-up showed that the palmar flexion degree,dorsiflexion degree,VAS score and Gartland-Werley score had no statistical difference be-tween the two groups(P>0.05).The incidence rates of postoperative incision infection,carpal tunnel syndrome and thumb extensor tendon rupture had no statistical differences between the two groups(P>0.05).Conclusion The two kinds of treatment method all have better clinical curative effect.The external fixation trestle treatment has the advantages of shorter operation time and shorter hospitalization time,while the volar locking compression titanium plate can reset the fractures under direct vision,is significantly su-perior to the external fixation trestle treatment in the aspects of recovery of palmar tilt angle,ulnar inclination angle and radial height,and is more suitable for the patients with unstable type C distal radius fracture..

Locking plate versus external fixation for type C distal radius fractures: A meta-analysis of randomized controlled trials / 中华创伤杂志(英文版)

<p><b>PURPOSE</b>Distal radial fracture is one of the most common fractures. Up to now, locking plates (LP) and external fixation (EF) are two conventional surgical approaches to type C radius fracture. Which method is superior has not yet reached a consensus. We try to assess the clinical effectiveness of the two interventions by this meta-analysis.</p><p><b>METHODS</b>We used network to search the PubMed, Embase, and Cochrane Medical Library of randomized controlled clinical trials about the type C distal radius fractures performed according to the search strategy mentioned in Cochrane Handbook 5.1.0 from Jan. 2005 to Jan. 2016. Patients in the experimental group were used LP, in the control group were included EF and other surgical approaches. Publication language was restricted to English. Studies that patient population and surgical indication did not define had been excluded. Studies must report at least one of the outcomes as follow: radial inclination, palmar tilt, ulnar variance, range of wrist flexion and extension, and range of wrist supination and pronation. The trials in which participants included children were excluded. We used Jadad study scores to appraise the study.</p><p><b>RESULTS</b>Seven studies included 162 patients (LP group) and 190 patients (EF group). We compared the radial inclination, palmar tilt, ulnar variance, range of wrist flexion and extension, and range of wrist supination and pronation. The radial inclination were revealed a difference favoring LP over EF [WMD = 1.84, 95% CI (0.17, 3.50), p = 0.03] and the palmar tilt and ulnar variance was no significant difference between the two groups [(WMD = 3.61, 95% CI (0.00, 7.23), p = 0.05; WMD = 0.05, 95% CI (-0.99, 1.09), p = 0.93]. The functional activities of range of flexion and extension and range of supination and pronation between the two groups was no difference [WMD = 10.04, 95% CI (-6.88, 26.96), p = 0.24; WMD = 12.53, 95% CI (-9.99, 35.06), p = 0.28].</p><p><b>CONCLUSION</b>Locking plate and external fixation is feasible to heal radius type C fracture. We found the small difference between the two groups on imaging examination. The locking plate has the advantage on maintaining reduction, however no significant difference regarding outcomes has been found between the two groups.</p>

Clinics in diagnostic imaging (191). Multiple system atrophy-cerebellar type (MSA-C)

A 49-year-old Chinese man was evaluated for progressive uncoordinated movements, dysphagia and urinary symptoms. Magnetic resonance imaging demonstrated a cruciform pattern of T2-weighted hyperintensity within the pons and selective atrophy of the cerebellar hemispheres and pons. The clinical history and radiological findings were consistent with a diagnosis of multiple system atrophy-cerebellar type. This article discussed the background, proposed mechanisms, diagnosis, radiological characteristics, prognosis and management of multiple system atrophy-cerebellar type.