Uterus transplantation from live donors became a reality to treat infertility following a successful Swedish 2014 series, inspiring uterus transplantation centres and programmes worldwide. However, ...no case of livebirth via deceased donor uterus has, to our knowledge, been successfully achieved, raising doubts about its feasibility and viability, including whether the womb remains viable after prolonged ischaemia.
In September, 2016, a 32-year-old woman with congenital uterine absence (Mayer-Rokitansky-Küster-Hauser MRKH syndrome) underwent uterine transplantation in Hospital das Clínicas, University of São Paulo, Brazil, from a donor who died of subarachnoid haemorrhage. The donor was 45 years old and had three previous vaginal deliveries. The recipient had one in-vitro fertilisation cycle 4 months before transplant, which yielded eight cryopreserved blastocysts.
The recipient showed satisfactory postoperative recovery and was discharged after 8 days' observation in hospital. Immunosuppression was induced with prednisolone and thymoglobulin and continued via tacrolimus and mycophenalate mofetil (MMF), until 5 months post-transplantation, at which time azathioprine replaced MMF. First menstruation occurred 37 days post-transplantation, and regularly (every 26–32 days) thereafter. Pregnancy occurred after the first single embryo transfer 7 months post-transplantation. No blood flow velocity waveform abnormalities were detected by Doppler ultrasound of uterine arteries, fetal umbilical, or middle cerebral arteries, nor any fetal growth impairments during pregnancy. No rejection episodes occurred after transplantation or during gestation. Caesarean delivery occurred on Dec 15, 2017, near gestational week 36. The female baby weighed 2550 g at birth, appropriate for gestational age, with Apgar scores of 9 at 1 min, 10 at 5 min, and 10 at 10 min, and along with the mother remains healthy and developing normally 7 months post partum. The uterus was removed in the same surgical procedure as the livebirth and immunosuppressive therapy was suspended.
We describe, to our knowledge, the first case worldwide of livebirth following uterine transplantation from a deceased donor in a patient with MRKH syndrome. The results establish proof-of-concept for treating uterine infertility by transplantation from a deceased donor, opening a path to healthy pregnancy for all women with uterine factor infertility, without need of living donors or live donor surgery.
Fundação de Amparo à Pesquisa do Estado de São Paulo and Hospital das Clínicas, University of São Paulo, Brazil.
Patients with cirrhosis have a high incidence of abdominal wall hernias and carry an elevated perioperative morbidity and mortality. The optimal surgical management strategy as well as timing of ...abdominal hernia repair remains controversial.
A cohort study of 67 cirrhotic patients who underwent hernia repair during the period of January 1998-December 2009 at the University Hospital of Sao Paulo were included. After meeting study criteria, a total of 56 patients who underwent 61 surgeries were included in the final analysis. Patient characteristics, morbidity (Clavien score), mortality, Child-Turcotte-Pugh score, MELD score, use of prosthetic material, and elective or emergency surgery have been analysed with regards to morbidity and 30-day mortality.
The median MELD score of the patient population was 14 (range: 6 to 24). Emergency surgery was performed in 34 patients because of ruptured hernia (n = 13), incarceration (n = 10), strangulation (n = 4), and skin necrosis or ulceration (n = 7). Elective surgery was performed in 27 cases. After a multivariable analysis, emergency surgery (OR 7.31; p 0.017) and Child-Pugh C (OR 4.54; p 0.037) were risk factors for major complications. Moreover, emergency surgery was a unique independent risk factor for 30-day mortality (OR 10.83; p 0.028).
Higher morbidity and mortality are associated with emergency surgery in advanced cirrhotic patients. Therefore, using cirrhosis as a contraindication for hernia repair in all patients may be reconsidered in the future, especially after controlling ascites and in those patients with hernias that are becoming symptomatic or show signs of possible skin necrosis and rupture. Future prospective randomized studies are needed to confirm this surgical strategy.
Setting up new liver transplant (LT) centers is essential for countries with organ shortages. However, good outcomes require experience, because LT learning depends on a high number of surgeries. ...This study aims to describe how a new center was set up from a partnership between the new center and an experienced one. The step-by-step preparation process, the time needed and the results of the new center are depicted.
The mentoring process lasted 40 months, in which half of the 52 patients included on the transplant list received LT. After the mentorship, a 22-month period was also analyzed, in which 46 new patients were added to the waiting list and nine were operated on.
The 30-day survival rates during (92.3%) and after (66.7%) the partnership were similar to the other LT centers in the same region, as well as the rates of longer periods. The waiting time on the LT list, the characteristics of the donors and the ischemia times did not differ during or after the mentorship.
The partnership between universities is a suitable way to set up LT centers, achieving good results for the institutions and the patients involved.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Post-traumatic lesions with transection of the facial nerve present limited functional outcome even after repair by gold-standard microsurgical techniques. Stem cell engraftment combined with ...surgical repair has been reported as a beneficial alternative. However, the best association between the source of stem cell and the nature of conduit, as well as the long-term postoperative cell viability are still matters of debate. We aimed to assess the functional and morphological effects of stem cells from human exfoliated deciduous teeth (SHED) in polyglycolic acid tube (PGAt) combined with autografting of rat facial nerve on repair after neurotmesis. The mandibular branch of rat facial nerve submitted to neurotmesis was repaired by autograft and PGAt filled with purified basement membrane matrix with or without SHED. Outcome variables were compound muscle action potential (CMAP) and axon morphometric. Animals from the SHED group had mean CMAP amplitudes and mean axonal diameters significantly higher than the control group (p < 0.001). Mean axonal densities were significantly higher in the control group (p = 0.004). The engrafted nerve segment resected 6 weeks after surgery presented cells of human origin that were positive for the Schwann cell marker (S100), indicating viability of transplanted SHED and a Schwann cell-like phenotype. We conclude that regeneration of the mandibular branch of the rat facial nerve was improved by SHED within PGAt. The stem cells integrated and remained viable in the neural tissue for 6 weeks since transplantation, and positive labeling for S100 Schwann-cell marker suggests cells initiated in vivo differentiation.
mutations are the leading cause of non-syndromic inherited hearing loss.
encodes connexin-26 (CX26), which is a connexin (CX) family protein expressed in cochlea, skin, liver, and brain, displaying ...short cytoplasmic N-termini and C-termini. We searched for CX26 C-terminus binding partners by affinity capture and identified 12 unique proteins associated with cell junctions or cytoskeleton (CGN, DAAM1, FLNB, GAPDH, HOMER2, MAP7, MAPRE2 (EB2), JUP, PTK2B, RAI14, TJP1, and VCL) by using mass spectrometry. We show that, similar to other CX family members, CX26 co-fractionates with TJP1, VCL, and EB2 (EB1 paralogue) as well as the membrane-associated protein ASS1. The adaptor protein CGN (cingulin) co-immuno-precipitates with CX26, ASS1, and TJP1. In addition, CGN co-immunoprecipitation with CX30, CX31, and CX43 indicates that CX association is independent on the CX C-terminus length or sequence. CX26, CGN, FLNB, and DAMM1 were shown to distribute to the organ of Corti and hepatocyte plasma membrane. In the mouse liver, CX26 and TJP1 co-localized at the plasma membrane. In conclusion, CX26 associates with components of other membrane junctions that integrate with the cytoskeleton.
Fragile X syndrome, the major cause of inherited intellectual disability among men, is due to deficiency of the synaptic functional regulator FMR1 protein (FMRP), encoded by the FMRP translational ...regulator 1 (FMR1) gene. FMR1 alternative splicing produces distinct transcripts that may consequently impact FMRP functional roles. In transcripts without exon 14 the translational reading frame is shifted. For deepening current knowledge of the differential expression of Fmr1 exon 14 along the rat nervous system development, we conducted a descriptive study employing quantitative RT-PCR and BLAST of RNA-Seq datasets.
We observed in the rat forebrain progressive decline of total Fmr1 mRNA from E11 to P112 albeit an elevation on P3; and exon-14 skipping in E17-E20 with downregulation of the resulting mRNA. We tested if the reduced detection of messages without exon 14 could be explained by nonsense-mediated mRNA decay (NMD) vulnerability, but knocking down UPF1, a major component of this pathway, did not increase their quantities. Conversely, it significantly decreased FMR1 mRNA having exon 13 joined with either exon 14 or exon 15 site A.
The forebrain in the third embryonic week of the rat development is a period with significant skipping of Fmr1 exon 14. This alternative splicing event chronologically precedes a reduction of total Fmr1 mRNA, suggesting that it may be part of combinatorial mechanisms downregulating the gene's expression in the late embryonic period. The decay of FMR1 mRNA without exon 14 should be mediated by a pathway different from NMD. Finally, we provide evidence of FMR1 mRNA stabilization by UPF1, likely depending on FMRP.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Although patients’ clinical conditions have been shown to be associated with coronavirus disease (COVID-19) severity and outcome, their impact on hospital costs are not known. This economic ...evaluation of COVID-19 admissions aimed to assess direct and fixed hospital costs and describe their particularities in different clinical and demographic conditions and outcomes in the largest public hospital in Latin America, located in São Paulo, Brazil, where a whole institute was exclusively dedicated to COVID-19 patients in response to the pandemic.
This is a partial economic evaluation performed from the hospital´s perspective and is a prospective, observational cohort study to assess hospitalization costs of suspected and confirmed COVID-19 patients admitted between March 30 and June 30, 2020, to Hospital das Clínicas of the University of São Paulo Medical School (HCFMUSP) and followed until discharge, death, or external transfer. Micro- and macro-costing methodologies were used to describe and analyze the total cost associated with each patient's underlying medical conditions, itinerary and outcomes as well as the cost components of different hospital sectors.
The average cost of the 3254 admissions (51.7% of which involved intensive care unit stays) was US$12,637.42. The overhead cost was its main component. Sex, age and underlying hypertension (US$14,746.77), diabetes (US$15,002.12), obesity (US$18,941.55), chronic renal failure (US$15,377.84), and rheumatic (US$17,764.61), hematologic (US$15,908.25) and neurologic (US$15,257.95) diseases were associated with higher costs. Age strata >69 years, reverse transcription polymerase chain reaction (RT-PCR)-confirmed COVID-19, comorbidities, use of mechanical ventilation or dialysis, surgery and outcomes remained associated with higher costs.
Knowledge of COVID-19 hospital costs can aid in the development of a comprehensive approach for decision-making and planning for future risk management.
A escrita narrativa de professoras e professores tem ocupado, com grande frequência, espaço nos debates e estudos da comunidade acadêmica do campo educacional. Entre diferentes discussões ...metodológicas e epistemológicas acerca de seus usos, limites e potencialidades, uma constância: o gênero narrativo parece ter ocupado um importante e definitivo espaço de diálogo e intercâmbio entre a comunidade acadêmica e da Educação Básica. Narram professores e professoras, em diferentes contextos e momentos, dando visibilidade a fragmentos cotidianos, nem sempre vistos e percebidos por outras frestas, que não a da narrativa de quem vive.
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