- Glycaemic control in diabetic rats treated with islet transplantation using plasma combined with hydroxypropylmethyl cellulose hydrogel. [Journal Article]Acta Biomater 2019AB
- Islet transplantation is one of the most efficient cell therapies used in clinics and could treat a large proportion of patients with diabetes. However, it is limited by the high requirement of pancreas necessary to provide the sufficient surviving islet mass in the hepatic tissue and restore normoglycaemia. Reduction in organ procurement requirements could be achieved by extrahepatic transplanta…
Islet transplantation is one of the most efficient cell therapies used in clinics and could treat a large proportion of patients with diabetes. However, it is limited by the high requirement of pancreas necessary to provide the sufficient surviving islet mass in the hepatic tissue and restore normoglycaemia. Reduction in organ procurement requirements could be achieved by extrahepatic transplantation using a biomaterial that enhances islet survival and function. We report a plasma-supplemented hydroxypropyl methylcellulose (HPMC) hydrogel, engineered specifically using a newly developed technique for intra-omental islet infusion, known as hOMING (h-Omental Matrix Islet filliNG). The HPMC hydrogel delivered islets with better performance than that of the classical intrahepatic infusion. After the validation of the HPMC suitability for islets in vivo and in vitro, plasma supplementation modified the rheological properties of HPMC without affecting its applicability with hOMING. The biomaterial association was proven to be more efficient both in vitro and in vivo, with better islet viability and function than that of the current clinical intrahepatic delivery technique. Indeed, when the islet mass was decreased by 25% or 35%, glycaemia control was observed in the group of plasma-supplemented hydrogels, whereas no regulation was observed in the hepatic group. Plasma gelation, observed immediately post infusion, decreased anoïkis and promoted vascularisation. To conclude, the threshold mass for islet transplantation could be decreased using HPMC-Plasma combined with the hOMING technique. The simplicity of the hOMING technique and the already validated use of its components could facilitate its transfer to clinics. Statement of significance One of the major limitations for the broad deployment of current cell therapy for brittle type 1 diabetes is the islets' destruction during the transplantation process. Retrieved from their natural environment, the islets are grafted into a foreign tissue, which triggers massive cell loss. It is mandatory to provide the islets with an optimised 3D environment specifically designed for islet implantation to improve cell therapy outcomes. For this aim, we combined HPMC and plasma. HPMC provides suitable rheological properties to the plasma to be injectable and maintained in the omentum. Afterwards, the plasma polymerises around the graft in vivo, thereby allowing their optimal integration into their transplantation site. As a result, the islet mass required to obtain glycaemic control was reduced by 35%.
- Topiramate prevents oxaliplatin-related axonal hyperexcitability and oxaliplatin induced peripheral neurotoxicity. [Journal Article]Neuropharmacology 2019; :107905N
- Oxaliplatin (OHP) Induced Peripheral Neurotoxicity (OIPN) is one of the dose-limiting toxicities of the drug and these adverse effects limit cancer therapy with L-OHP, used for colorectal cancer treatment. Acute neurotoxicity consists of symptoms that are the hallmarks of a transient axonal hyperexcitability; chronic neurotoxicity has a clinical picture compatible with a length-dependent sensory …
Oxaliplatin (OHP) Induced Peripheral Neurotoxicity (OIPN) is one of the dose-limiting toxicities of the drug and these adverse effects limit cancer therapy with L-OHP, used for colorectal cancer treatment. Acute neurotoxicity consists of symptoms that are the hallmarks of a transient axonal hyperexcitability; chronic neurotoxicity has a clinical picture compatible with a length-dependent sensory neuropathy. Acute OIPN pathogenesis has been linked to sodium voltage-operated channels (Na + VOC) dysfunction and it has been advocated as a possible predisposing factor to chronic neurotoxicity. We tested if topiramate (TPM), a well-known Na + VOC modulator, was able to modify acute as well as chronic OIPN. The project was divided into two parts. In Experiment 1 we tested by means of Nerve Excitability Testing (NET) a cohort of female Wistar rats to assess TPM effects after a single OHP administration (5 mg/kg, iv). In Experiment 2 we assessed TPM effects after chronic OHP treatment (5 mg/kg, 2qw4ws, iv) using NET, nerve conduction studies (NCS), behavioral tests and neuropathology (caudal nerve morphometry and morphology and Intraepidermal Nerve Fiber [IENF] density). In Experiment 1 TPM was able to prevent OHP effects on Na + VOC: OHP treatment induced a highly significant reduction of the sensory nerve's threshold, during the superexcitability period (p-value = 0.008), whereas TPM co-administration prevented this effect. In Experiment 2 we verified that TPM was able to prevent not only acute phenomena, but also to completely prevent chronic OIPN. This latter observation was supported by a multimodal approach: in fact, only OHP group showed altered findings compared to CTRL group at a neurophysiological (proximal caudal nerve sensory nerve action potential [SNAP] amplitude, p-value = 0.001; distal caudal nerve SNAP amplitude, p-value<0.001, distal caudal nerve sensory conduction velocity, p-value = 0.04), behavioral (mechanical threshold, p-value 0.003) and neuropathological levels (caudal nerve fibers density, p-value 0.001; IENF density, p-value <0.001). Our data show that TPM is a promising drug to prevent both acute and chronic OIPN. These findings have a high translational potential, since they were obtained using outcome measures that match clinical practice and TPM is already approved for clinical use being free from detrimental interaction with OHP anticancer properties.
- Minimal invasive pocket technique for magnet bone implant hearing aid without fixation. [Journal Article]Eur Arch Otorhinolaryngol 2019EA
- CONCLUSIONS: The minimally subperiosteal pocket surgical technique MIP without fixation and with tissue preservation for the MBIHA is safe, rapid and effective for patients with conductive or mixed hearing loss. It opens new perspectives of development and modify conventional concept in magnetic coupling of bone-conducted device.
- A new strategy to confirm the identity of tumour tissues using single-nucleotide polymorphisms and next-generation sequencing. [Journal Article]Int J Legal Med 2019IJ
- With growing cancer morbidity, forensics cases in which archived tumour tissues can be used as biological samples are increasing, and an effective method to identify the body source of tumour tissues is needed. Single nucleotide polymorphisms (SNPs) may be a promising biomarker to identify the source of tumour tissues because of their low mutation rate and small amplicon size. Next-generation seq…
With growing cancer morbidity, forensics cases in which archived tumour tissues can be used as biological samples are increasing, and an effective method to identify the body source of tumour tissues is needed. Single nucleotide polymorphisms (SNPs) may be a promising biomarker to identify the source of tumour tissues because of their low mutation rate and small amplicon size. Next-generation sequencing techniques offers the ability to detect hundreds of SNPs in a single run. The Precision ID Identity Panel (Thermo Fisher Scientific, Waltham, MA, USA) detects 90 autosomal SNPs for individual identification and 34 lineage-informative SNPs on Y chromosome using the Ion PGM system (Thermo Fisher Scientific). In this study, we evaluated performance of the panel for individual identification of tumour tissues. One hundred and fifty pairs of tumour tissues and corresponding normal tissues were analysed. Loss of heterozygosity was detected only in tumour tissues. The identity-by-state (IBS) scoring system was adopted to identify the body source of tumour tissues. The IBS score, as well as the number of loci with 2 alleles (A2), 1 allele (A1) and 0 alleles (A0) shared, were analysed within each tumour-normal pair, unrelated individual pairs, parent-offspring pairs and full-sibling pairs. According to the probability distribution, threshold of A2 in the range of 69 to 89 could achieve accuracy > 99% in identifying the source of tumour tissues. Thus, we developed a new strategy (process and criteria) to identify the source of tumour tissues that could be used in practice.
- Microsurgical Resection of the IV Ventricle Subependymoma: 2-Dimensional Operative Video. [Journal Article]Oper Neurosurg (Hagerstown) 2019ON
- In this video, we demonstrate microsurgical resection of IV ventricle subependymoma. To the best of our knowledge, this is the first video case report of a microsurgical resection of subependymoma of the IV ventricle in the peer-reviewed English literature. Subependymomas are benign central nervous system tumors, typically arising in ventricular spaces, mostly in the IV and lateral ventricles.1-3…
In this video, we demonstrate microsurgical resection of IV ventricle subependymoma. To the best of our knowledge, this is the first video case report of a microsurgical resection of subependymoma of the IV ventricle in the peer-reviewed English literature. Subependymomas are benign central nervous system tumors, typically arising in ventricular spaces, mostly in the IV and lateral ventricles.1-3 They are isointense on T1 and hyperintense on T2-weighted magnetic resonance imaging (MRI) with minimal or no enhancement.4 Microsurgery remains the mainstay treatment. Complete tumor resection is possible and curative with excellent prognosis.1,5-7 Although the clinical course appears benign, the inability to diagnose them radiographically with certainty and the possibility of an alternative malignant lesion support a low threshold for early and safe resection.8 A 39-yr-old man presented with severe headache and balance problems. Pre- and postcontrast neuroaxis MRI revealed a centrally located IV ventricle lesion without hydrocephalus. The aim of the surgery was complete tumor resection. Surgery was performed in the prone position by the senior author (KIA) with intraoperative neurophysiology monitoring. A small suboccipital craniotomy and C1 posterior arch removal was done. After opening the dura and arachnoid membrane, the tumor was identified and meticulously dissected from the adjacent posterior inferior cerebellar artery and the floor of the fourth ventricle and from brain stem white matter at the tumor-neural tissue interface to avoid brainstem interference. Histological analysis revealed subependymoma (World Health Organization Grade I). Postoperative pre- and postcontrast MRI revealed complete resection. Headache and balance problems completely resolved; the patient was neurologically intact. The patient provided written consent and permission to publish his image.
- Lumbar neuraxial procedures in thrombocytopenic patients across populations: A systematic review and meta-analysis. [Journal Article]J Clin Anesth 2019; :109666JC
- CONCLUSIONS: Spinal epidural hematoma in thrombocytopenic patients is rare. In this sample of patients, an inflection point and narrow confidence intervals are observed near a platelet count of 75,000 × 106/L or above, reflecting an estimated low spinal epidural hematoma event rate with more certainty given a larger sample size and inclusion of spinal epidural hematoma cases. Thrombocytopenic patients should be monitored, particularly in the first 48 h, and educated about symptoms concerning for spinal epidural hematoma.
- Transcutaneous Tibial Nerve Stimulation for Treating Neurogenic Lower Urinary Tract Dysfunction: A Pilot Study for an International Multicenter Randomized Controlled Trial. [Journal Article]Eur Urol Focus 2019EU
- CONCLUSIONS: All procedures were feasible and well tolerated by all nine patients. Using verum TTNS, a motor response could be triggered in all patients and a sensory response in all but one. At the beginning and end of treatment, seven and six (78% and 67%) patients believed to receive verum TTNS, and five and six (56% and 67%) correctly guessed their group allocation, respectively. No treatment-related adverse events occurred. A comparison of baseline versus 6 wks of verum and sham TTNS led to relevant symptom and functional changes in only a limited number of piloted patients.Verum and sham TTNS combined with the blinding procedures proved feasible and safe. Both interventions and procedures, as well as the randomization process, were well accepted by the patients. While the subsensory threshold TTNS approach in combination with the sham condition is advantageous for patients' blinding, the clinical findings raised some doubt regarding sufficient TNS. Hence, relevant methodological adjustments concerning the adequate stimulation current and corresponding sham condition are needed before starting randomized controlled trials to clarify the value and role of TTNS in neuro-urology.
- Mesorhizobium intechi sp. nov. isolated from nodules of Lotus tenuis in soils of the Flooding Pampa, Argentina. [Journal Article]Syst Appl Microbiol 2019; :126044SA
- Three symbiotic nitrogen-fixing bacteria (BD68T, BD66 and BD73) isolated from root nodules of Lotus tenuis in lowland soils of the Flooding Pampa (Argentina), previously classified as members of the Mesorhizobium genus, were characterized in this study. Phylogenetic analysis of their 16S rRNA gene sequences showed a close relationship to M. japonicum MAFF 303099T, M. erdmanii USDA 3471T, M. carmi…
Three symbiotic nitrogen-fixing bacteria (BD68T, BD66 and BD73) isolated from root nodules of Lotus tenuis in lowland soils of the Flooding Pampa (Argentina), previously classified as members of the Mesorhizobium genus, were characterized in this study. Phylogenetic analysis of their 16S rRNA gene sequences showed a close relationship to M. japonicum MAFF 303099T, M. erdmanii USDA 3471T, M. carmichaelinearum ICMP 18942T, M. opportunistum WSM 2975T and M. jarvisii ATCC 33699T, with sequence identities of 99.72%-100%. Multilocus sequence analysis of other housekeeping genes revealed that the three isolates belonged to a phylogenetically distinct clade within the genus Mesorhizobium. Strain BD68T was designated as the group representative and its genome was fully sequenced. The average nucleotide identity and in silico DNA-DNA hybridization comparisons between BD68T and the most related type strains showed values below the accepted threshold for species discrimination. Phenotypic and chemotaxonomic features were also studied. Based on these results, BD68T, BD66 and BD73 could be considered to represent a novel species of the genus Mesorhizobium, for which the name Mesorhizobium intechi sp. nov. is hereby proposed. The type strain of this species is BD68T (=CECT 9304T=LMG 30179T).
- Pharmacokinetic-pharmacodynamic modelling of the antinociceptive effect of a romifidine infusion in standing horses. [Journal Article]Vet Anaesth Analg 2019VA
- CONCLUSIONS: Romifidine elicited a marked antinociceptive effect. Romifidine-induced antinociception appeared with a delayed onset and lasted longer than sedation after discontinuing its administration.
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- Screening for Asymptomatic Coronary Artery Disease in Waitlisted Kidney Transplant Candidates: A Cost-Utility Analysis. [Journal Article]Am J Kidney Dis 2019AJ
- CONCLUSIONS: Rates of cardiovascular events in waitlisted candidates and transplant recipients are limited in the contemporary era. The results may not be generalizable to populations outside Australia and New Zealand.No further screening for CAD after waitlisting is likely to be cost-effective and may improve survival. Precision around CAD prevalence estimates and health care resource use will reduce existing uncertainty.