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Background: "Convex Pedicle Screw Technique" reduces the theoretical risk of neurovascular injury. Our aim is to evaluate the efficacy of this technique in patients with neuromuscular scoliosis (NMS). Methods: Retrospective study of 12 patients who underwent a Convex Pedicle Screw Technique and were diagnosed with NMS. Patients who had undergone previous spinal surgery were excluded. The minimum follow-up required was 24 months. Demographic data, intraoperative data, neurovascular complications and neurophysiological events requiring implant repositioning, as well as pre- and postoperative radiological variables were collected. Results: Twelve patients diagnosed with NMS underwent surgery. The median operative time was 217 minutes. Mean blood loss was 3.8±1.1 g/dL hemoglobin (Hb). The median postoperative stay was 8.8±4 days. A reduction of the Cobb angle in primary curve of 49.1% (from 52.8°±18° to 26.5°±12.6°; P<0.001) and in secondary curve of 25.2% (from 27.8°±18.9° to 18.3°±13.3°; P=0.10) was achieved. Coronal balance improved by 69.4% (7.5±46.2 vs. 2.3±20.9 mm; P=0.72) and sagittal balance by 75% (from -14.1±71.8 vs. -3.5±48.6 mm; P=0.50). There were no neurovascular complications. There were no intraoperative neurophysiological events requiring implant repositioning, nor during reduction maneuvers. No infections were reported. Conclusions: The correction of the deformity from convexity in NMS achieves similar results to other techniques, and a very low complication rate.
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Scheuermann´s kyphosis (SK) is the most common cause of painful and progressive structural hyperkyphosis in adolescents. Surgical treatment should be considered in cases of refractory pain or progressive deformities. We present the clinical and radiological results obtained using a bipolar, hybrid posterior instrumentation tecnique. We analysed 12 males and 6 females, with mean age of 15.8 years. Minimum follow-up was 2 years. We used transverse process hooks at the cranial level and polyaxial screws for the remaining levels. We did not instrument the periapical segment. We used the sagittal stable vertebra (SSV) as the lower instrumented vertebra (LIV) in most cases, the "barely touched SSV" if the above disc space is lordotic. The mean preoperative kyphosis was 73.6º, mean postoperative kyphosis 44.7º, and mean correction of 28.9º (p = 0.0002). The mean reduction in lumbar lordosis (LL) was 8.9º (p = 0.0018). There were no significant differences in the spinopelvic parameters or sagittal balance. The mean number of instrumented levels was 8.9. Type II osteotomies were necessary in only three patients. Three patients had a cranial sagittal angle greater than 10°, all of them asymptomatic. Postoperatively, all patients had VAS scores less than 2 and SRS-22 scores greater than 4. Hybrid bipolar posterior instrumentation offers adequate curve correction, less operative time, implant density, bleeding, material protrusion and risk of spinal cord injury, leaving a large periapical bed for graft supply. We propose to measure the flexibility of the curve in MRI. In flexible curves (those that correct at least 20% in the supine decubitus position), wide facetectomies offer adequate correction of the deformity.
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Cereblon/CRBN is a substrate-recognition component of the Cullin4A-DDB1-Roc1 E3 ubiquitin ligase complex. Destabilizing mutations in the human CRBN gene cause a form of autosomal recessive non-syndromic intellectual disability (ARNSID) that is modelled by knocking-out the mouse Crbn gene. A reduction in excitatory neurotransmission has been proposed as an underlying mechanism of the disease. However, the precise factors eliciting this impairment remain mostly unknown. Here we report that CRBN molecules selectively located on glutamatergic neurons are necessary for proper memory function. Combining various in vivo approaches, we show that the cannabinoid CB1 receptor (CB1R), a key suppressor of synaptic transmission, is overactivated in CRBN deficiency-linked ARNSID mouse models, and that the memory deficits observed in these animals can be rescued by acute CB1R-selective pharmacological antagonism. Molecular studies demonstrated that CRBN interacts physically with CB1R and impairs the CB1R-Gi/o-cAMP-PKA pathway in a ubiquitin ligase-independent manner. Taken together, these findings unveil that CB1R overactivation is a driving mechanism of CRBN deficiency-linked ARNSID and anticipate that the antagonism of CB1R could constitute a new therapy for this orphan disease.
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Proteínas Adaptadoras de Transdução de Sinal , Transtornos da Memória , Ubiquitina-Proteína Ligases , Animais , Camundongos , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Mutação , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Receptor CB1 de Canabinoide/genética , Receptor CB1 de Canabinoide/metabolismo , Transtornos da Memória/genética , Transtornos da Memória/metabolismoRESUMO
The present work investigated the manufacture of elements such as water tanks from recycled concrete for applications where industries require water heating. This proposal leverages precast rejects for recycled concrete and incorporates colouring pigments. It is expected to contribute to the circularity of construction materials (due to the total replacement of natural aggregates by recycled aggregates) as well as to energy and emissions savings, which are attributed to improved thermal performance driven by the thermal behaviour that the coloration pigment gives to the manufactured concrete elements. To assess the efficacy of the proposed solution, on the one hand, mechanical tests were carried out in tensile, compression and modulus of elasticity, which showed a suitable concrete dosage for HA-30 structural concrete. Simultaneously, in search for a material that would increase the internal temperature of the tanks, thermal tests were carried out in a controlled laboratory environment on samples with different percentages of pigment, and an optimum concentration of 1% was obtained. It was also found that the thermal conductivity remained almost unaffected. Finally, two water tank prototypes were manufactured and tested under real environmental conditions: one with the optimised pigment concentration solution and other (the reference tank) without pigment. The results revealed that the colourised tank with the optimal concentration resulted in an average water temperature increase of 2 °C with respect to the reference tank. Finally, the economic and environmental benefits of this temperature increase were studied for industrial processes requiring water heating with a potential saving of 8625 kWh per month.
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INTRODUCTION: Description of a new surgical procedure (percutaneous lengthening and arthroscopic release, PLAR) that combines all the possible interventions on the iliotibial band (ITB), and evaluates its outcomes in a group of distance runners diagnosed with ITBS. METHODS: A prospective observational study was made of distance runners diagnosed with ITBS and operated upon using the PLAR technique between 1 and 2018 and 31 June 2020. The surgical technique is described in detail, and the demographic data and functional outcomes measured by the sports performance scales Activity Rating Scale (ARS) and International Knee Documentation Committee (IKDC) are presented. RESULTS: A total of 14 patients were included, with a mean follow-up of 16 months (range 12-42 months). All the patients resumed their previous sporting activity after an average of 4 (range 2.5-6) months, and no complications were recorded. In all cases, statistically significant improvement was evidenced by the ARS and IKDC scales following PLAR (p < 0.001), with excellent outcomes in 71% of the cases according to the ARS scale and in 86% according to the IKDC scale (mean difference between preoperative and final follow-up scores of 12.1/16 and 34.2/100 points, respectively). CONCLUSION: The PLAR technique is effective in allowing a return to previous sports performance levels in a short period of time among patients with ITBS refractory to conservative management, with a high satisfaction rate and the absence of complications.
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Melanoma is one of the deadliest forms of cancer. Most melanoma deaths are caused by distant metastases in several organs, especially the brain, the so-called melanoma brain metastases (MBMs). However, the precise mechanisms that sustain the growth of MBMs remain elusive. Recently, the excitatory neurotransmitter glutamate has been proposed as a brain-specific, pro-tumorigenic signal for various types of cancers, but how neuronal glutamate shuttling onto metastases is regulated remains unknown. Here, we show that the cannabinoid CB1 receptor (CB1R), a master regulator of glutamate output from nerve terminals, controls MBM proliferation. First, in silico transcriptomic analysis of cancer-genome atlases indicated an aberrant expression of glutamate receptors in human metastatic melanoma samples. Second, in vitro experiments conducted on three different melanoma cell lines showed that the selective blockade of glutamatergic NMDA receptors, but not AMPA or metabotropic receptors, reduces cell proliferation. Third, in vivo grafting of melanoma cells in the brain of mice selectively devoid of CB1Rs in glutamatergic neurons increased tumour cell proliferation in concert with NMDA receptor activation, whereas melanoma cell growth in other tissue locations was not affected. Taken together, our findings demonstrate an unprecedented regulatory role of neuronal CB1Rs in the MBM tumour microenvironment.
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Background: Ruminococcus gnavus (R. Gnavus) is an anaerobic Gram-positive coccus, common commensal of the gastrointestinal tract of animals and humans. Anaerobic organisms as etiologic agents of bone and joint infections (BJI) are uncommon and frequently underestimated. New technologies, such as mass spectrometry techniques and molecular techniques like 16S rRNA, allow for more efficient diagnosis of these anaerobic bacteria. We present the first case report of deep surgical site infection (SSI) due to R. Gnavus, following spinal surgery. Case Description: We report the case of a deep SSI caused by R. Gnavus following posterior spinal instrumentation in an 81-year-old woman. The patient underwent extension of her previous fusion L2-L5, due to adjacent segment disease (ASD). We performed a T10 to S2-alar-iliac instrumentation. During the postoperative period, the patient presented with a paralytic ileus that required the placement of a nasogastric tube followed by gastrointestinal bleeding and two gastroscopies. Subsequently the patient showed signs of deep SSI. We performed surgical irrigation and debridement. All six cultures in anaerobic media showed short Gram-positive diplococci, using matrix-assisted laser desorption/ionization time of flight mass spectrometry (Maldi-TOF MS) all six strains were identified as R. Gnavus. The patient was treated with amoxicilin 1 g/8 h and ciprofloxacin 750 mg/12 h for 4 weeks. Six months postoperative, she was asymptomatic. Conclusions: As is the case with our patient, all previously described cases of R. Gnavus infection had a history of intestinal disease or immunosupression. We believe the isolation of R. Gnavus should raise the possibility of intestinal injury. Immunosuppression is also an important risk factor for the development of R. Gnavus infection.
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Background: Cerebrospinal fluid leakage can cause abducens nerve palsy (ANP) secondary to downward brain traction, caused by intracranial hypotension. We present the first case after cervical fixation and fusion with spinal cord decompression. Case Description: We present a 65-year-old male, who undergone C5-C6 decompression by laminectomy and C3-T2 fixation and fusion, without intraoperative complications. Two months later, the patient referred a 2-week history of diplopia, with no other accompanying symptom. Clinical examination revealed a lack of lateral gaze of the left eye. Cervical MRI disclosed findings compatible with pseudomeningocele. Given the time of evolution, the subacute clinical findings and the absence of image or clinical data of infection or intracranial hypotension, we decided to perform conservative treatment. We submitted the patient to periodic clinical examinations and we confirmed progressive clinical improvement of diplopia, in association with neurologic and ophthalmologic specialists. At this time, six months after surgery, the patient is asymptomatic. The swelling has significantly decreased in size. Control MRI revealed no growth of the pseudomeningocele. Conclusions: ANP secondary to intracranial hypotension after cervical spine surgery requires immediate imaging tests and clinical evaluation from neurology and ophthalmology specialists. Management can be conservative, as long as diplopia is the only clinical and radiological finding and wound does not show signs of infection.
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Background: Nutritional and inflammation status are significant predictors of morbidity and mortality risk in advanced chronic kidney disease (ACKD). To date, there are a limited number of clinical studies on the influence of nutritional status in ACKD stages 4-5 on the choice of renal replacement therapy (RRT) modality. Aim: This study aimed to examine relationships between comorbidity and nutritional and inflammatory status and the decision-making on the choice of RRT modalities in adults with ACKD. Methods: A retrospective cross-sectional study was conducted on 211 patients with ACKD with stages 4-5 from 2016 to 2021. Comorbidity was assessed using the Charlson comorbidity index (CCI) according to severity (CCI: ≤ 3 and >3 points). Clinical and nutritional assessment was carried out by prognosis nutritional index (PNI), laboratory parameters [serum s-albumin, s-prealbumin, and C-reactive protein (s-CRP)], and anthropometric measurements. The initial decision-making of the different RRT modalities [(in-center, home-based hemodialysis (HD), and peritoneal dialysis (PD)] as well as the informed therapeutic options (conservative treatment of CKD or pre-dialysis living donor transplantation) were recorded. The sample was classified according to gender, time on follow-up in the ACKD unit (≤ 6 and >6 months), and the initial decision-making of RRT (in-center and home-RRT). Univariate and multivariate regression analyses were carried out for evaluating the independent predictors of home-based RRT. Results: Of the 211 patients with ACKD, 47.4% (n = 100) were in stage 5 CKD, mainly elderly men (65.4%). DM was the main etiology of CKD (22.7%) together with hypertension (96.6%) as a CV risk factor. Higher CCI scores were significantly found in men, and severe comorbidity with a CCI score > 3 points was 99.1%. The mean time of follow-up time in the ACKD unit was 9.6 ± 12.8 months. A significantly higher CCI was found in those patients with a follow-up time > 6 months, as well as higher mean values of eGFR, s-albumin, s-prealbumin, s-transferrin, and hemoglobin, and lower s-CRP than those with a follow-up <6 months (all, at least p < 0.05). The mean PNI score was 38.9 ± 5.5 points, and a PNI score ≤ 39 points was found in 36.5%. S-albumin level > 3.8 g/dl was found in 71.1% (n = 150), and values of s-CRP ≤ 1 mg/dl were 82.9% (n = 175). PEW prevalence was 15.2%. The initial choice of RRT modality was higher in in-center HD (n = 119 patients; 56.4%) than in home-based RRT (n = 81; 40.5%). Patients who chose home-based RRT had significantly lower CCI scores and higher mean values of s-albumin, s-prealbumin, s-transferrin, hemoglobin, and eGFR and lower s-CRP than those who chose in-center RRT (p < 0.001). Logistic regression demonstrated that s-albumin (OR: 0.147) and a follow-up time in the ACKD unit >6 months (OR: 0.440) were significantly associated with the likelihood of decision-making to choose a home-based RRT modality (all, at least p < 0.05). Conclusion: Regular monitoring and follow-up of sociodemographic factors, comorbidity, and nutritional and inflammatory status in a multidisciplinary ACKD unit significantly influenced decision-making on the choice of RRT modality and outcome in patients with non-dialysis ACKD.
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BACKGROUND: The organizational structure of maternity services determines the choice of which professionals provide care during pregnancy, birth, and the postnatal period, and it influences the kind of care they deliver and the level of continuity of care offered. There is considerable evidence that demonstrates a relationship between how care is provided and the maternal and neonatal health outcomes. Registered midwives and obstetricians provide maternity care across Spain. To date, no studies have assessed whether maternity outcomes differ between these two groups. OBJECTIVE: The aim of this study was to examine the association between the care received (midwifery care versus obstetric care) and the maternal and neonatal outcomes in women with normal, low- and medium-risk pregnancies in Spain from 2016 to 2019. DESIGN: A prospective, multicentre, cross-sectional study was carried out as part of COST Action IS1405 at 44 public hospitals in Spain in the years 2016-2019. The protocol can be accessed through the registry ISRCTN14062994. The sample size of this study was 11,537 women. The primary outcome was mode of birth. The secondary outcomes included augmentation with oxytocin, use of epidural analgesia, women's position at birth, perineal integrity, third stage of labour management, maternal and neonatal admission to intensive care, Apgar score, neonatal resuscitation, and early initiation of breastfeeding. Chi-square tests for categorical variables and independent sample t-test for continuous variables to assess differences between the midwifery and obstetric groups were calculated. Odds ratio with intervals of confidence at 95% were calculated for obstetric interventions and perinatal outcomes. A multivariate logistic regression model was applied in order to examine the effect of type of healthcare provider on perinatal outcomes. These models were adjusted for care provider, type of onset of labour, use of anaesthesia, pregnancy risk, maternal age, parity, and gestational age at birth. RESULTS: Midwifery care was associated with lower rates of operative births and severe perineal damage and had no higher adverse outcomes. No statistically significant differences were observed in the use of other obstetric interventions between the two groups. CONCLUSIONS: The findings of this study should encourage a shift in the current maternity care system towards a greater integration of midwifery-led services in order to achieve optimal birth outcomes for women and newborns. REGISTRY NUMBER: ISRCTN14062994.
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Serviços de Saúde Materna , Tocologia , Estudos Transversais , Parto Obstétrico , Feminino , Humanos , Recém-Nascido , Gravidez , Resultado da Gravidez , Estudos Prospectivos , Ressuscitação , EspanhaRESUMO
AIMS: To assess the efficacy of a prompted voiding programme for restoring urinary continence at discharge in hospitalized older adults who presented with reversible urinary incontinence (UI) on admission to a functional recovery unit (FRU). To assess the maintenance of the outcomes achieved after hospitalization. To identify modifiable and unmodifiable factors associated with the success of the prompted voiding programme. DESIGN: Quasi-experimental, pre-/post-intervention study without a control group. METHODS: Participants were aged 65 and over with a history of reversible UI in the previous year who had been admitted to a FRU and were on a prompted voiding programme throughout their hospitalization period. The sample consisted of 221 participants. A non-probabilistic sampling method, in order of recruitment after signing the informed consent form, was used. The primary outcomes were UI assessed at discharge and 1 month, 3 months and 6 months after discharge. Funding was granted in July 2019 by the Spain Health Research Fund (PI19/00168, Ministry of Health). The proposal was approved by the Spanish Research Ethics Committee. DISCUSSION: The prompted voiding programme described can reverse UI or decrease the frequency and amount of urine loss in hospitalized older adults. IMPACT: Urinary incontinence is highly prevalent in hospitalized older adults. There is a need for care aimed at prevention, recovery and symptom control. Prompted voiding is a therapy provided by the nursing team during hospitalization and can also be provided by family caregivers at home after receiving proper training by the nursing team. Prompted voiding will enhance the health, functional ability and quality of life of older adults with UI, resulting in the reduction of associated healthcare costs and the risk of developing complications.
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Qualidade de Vida , Incontinência Urinária , Atividades Cotidianas , Idoso , Humanos , Espanha , MicçãoRESUMO
This research focuses on the study of the ruins of a large building known as "El Torreón" (the Tower), belonging to the Ulaca oppidum (Solosancho, Province of Ávila, Spain). Different remote sensing and geophysical approaches have been used to fulfil this objective, providing a better understanding of the building's functionality in this town, which belongs to the Late Iron Age (ca. 300-50 BCE). In this sense, the outer limits of the ruins have been identified using photogrammetry and convergent drone flights. An additional drone flight was conducted in the surrounding area to find additional data that could be used for more global interpretations. Magnetometry was used to analyze the underground bedrock structure and ground penetrating radar (GPR) was employed to evaluate the internal layout of the ruins. The combination of these digital methodologies (surface and underground) has provided a new perspective for the improved interpretation of "El Torreón" and its characteristics. Research of this type presents additional guidelines for better understanding of the role of this structure with regards to other buildings in the Ulaca oppidum. The results of these studies will additionally allow archaeologists to better plan future interventions while presenting new data that can be used for the interpretation of this archaeological complex on a larger scale.
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BACKGROUND: The COVID-19 pandemic is a public health challenge that puts health systems in a highly vulnerable situation. Nurses in critical care units (CCUs) and hospital emergency services (HESs) have provided care to patients with COVID-19 under pressure and uncertainty. OBJECTIVE: To identify needs related to safety, organisation, decision-making, communication and psycho-socio-emotional needs perceived by critical care and emergency nurses in the region of Madrid, Spain, during the acute phase of the epidemic crisis. METHODS: This is a cross-sectional study (the first phase of a mixed methods study) with critical care and emergency nurses from 26 public hospitals in Madrid using an online questionnaire. RESULTS: The response rate was 557, with 37.5% reporting working with the fear of becoming infected and its consequences, 28.2% reported elevated workloads, high patient-nurse ratios and shifts that did not allow them to disconnect or rest, while taking on more responsibilities when managing patients with COVID-19 (23.9%). They also reported deficiencies in communication with middle management (21.2%), inability to provide psycho-social care to patients and families and being emotionally exhausted (53.5%), with difficulty in venting emotions (44.9%). CONCLUSIONS: Critical care and emegency nurses may be categorised as a vulnerable population. It is thus necessary to delve deeper into further aspects of their experiences of the pandemic.
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Atitude do Pessoal de Saúde , Esgotamento Profissional/psicologia , COVID-19/enfermagem , Enfermagem de Cuidados Críticos , Enfermagem em Emergência , Enfermeiras e Enfermeiros , Carga de Trabalho , Adulto , Comunicação , Cuidados Críticos , Estudos Transversais , Atenção à Saúde , Serviço Hospitalar de Emergência , Família , Feminino , Administradores Hospitalares , Hospitais Públicos , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Avaliação das Necessidades , Enfermeiros Administradores , Enfermeiras e Enfermeiros/psicologia , Gestão de Recursos Humanos , Descanso/psicologia , SARS-CoV-2 , Espanha , Adulto JovemRESUMO
BACKGROUND: In Europe, the majority of healthy women give birth at conventional obstetric units with the assistance of registered midwives. This study examines the relationships between the intrapartum transfer of care (TOC) from midwife to obstetrician-led maternity care, obstetric unit size (OUS) with different degrees of midwifery autonomy, intrapartum interventions and birth outcomes. METHODS: A prospective, multicentre, cross-sectional study promoted by the COST Action IS1405 was carried out at eight public hospitals in Spain and Ireland between 2016-2019. The primary outcome was TOC. The secondary outcomes included type of onset of labour, oxytocin stimulation, epidural analgesia, type of birth, episiotomy/perineal injury, postpartum haemorrhage, early initiation of breastfeeding and early skin-to-skin contact. A logistic regression was performed to ascertain the effects of studied co-variables on the likelihood that participants had a TOC; Results: Out of a total of 2,126 low-risk women, those whose intrapartum care was initiated by a midwife (1772) were selected. There were statistically significant differences between TOC and OUS (S1 = 29.0%, S2 = 44.0%, S3 = 52.9%, S4 = 30.2%, p < 0.001). Statistically differences between OUS and onset of labour, oxytocin stimulation, type of birth and episiotomy or perineal injury were observed (p = 0.009, p < 0.001, p < 0.001, p < 0.001 respectively); Conclusions: Findings suggest that the model of care and OUS have a significant effect on the prevalence of intrapartum TOC and the birth outcomes. Future research should examine how models of care differ as a function of the OUS in a hospital, as well as the cost-effectiveness for the health care system.
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Parto Obstétrico , Tocologia , Unidade Hospitalar de Ginecologia e Obstetrícia , Estudos Transversais , Atenção à Saúde/estatística & dados numéricos , Parto Obstétrico/estatística & dados numéricos , Feminino , Humanos , Recém-Nascido , Irlanda , Serviços de Saúde Materna/estatística & dados numéricos , Tocologia/estatística & dados numéricos , Unidade Hospitalar de Ginecologia e Obstetrícia/estatística & dados numéricos , Gravidez , Estudos Prospectivos , Espanha/epidemiologiaRESUMO
The recreational and medical use of cannabis is largely increasing worldwide. Cannabis use, however, can cause adverse side effects, so conducting innovative studies aimed to understand and potentially reduce cannabis-evoked harms is important. Previous research conducted on cultured neural cells had supported that CNR1/CB1R (cannabinoid receptor 1), the main molecular target of cannabis, affects macroautophagy/autophagy. However, it was not known whether CNR1 controls autophagy in the brain in vivo, and, eventually, what the functional consequences of a potential CNR1-autophagy connection could be. We have now found that Δ9-tetrahydrocannabinol (THC), the major intoxicating constituent of cannabis, impairs autophagy in the mouse striatum. Administration of autophagy activators (specifically, the rapalog temsirolimus and the disaccharide trehalose) rescues THC-induced autophagy inhibition and motor dyscoordination. The combination of various genetic strategies in vivo supports the idea that CNR1 molecules located on neurons belonging to the direct (striatonigral) pathway are required for the autophagy- and motor-impairing activity of THC. By identifying autophagy as a mechanistic link between THC and motor performance, our findings may open a new conceptual view on how cannabis acts in the brain.
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Canabinoides , Animais , Autofagia , Encéfalo , Dronabinol/farmacologia , CamundongosRESUMO
The use of cannabis is rapidly expanding worldwide. Thus, innovative studies aimed to identify, understand and potentially reduce cannabis-evoked harms are warranted. Here, we found that Δ9-tetrahydrocannabinol, the psychoactive ingredient of cannabis, disrupts autophagy selectively in the striatum, a brain area that controls motor behavior, both in vitro and in vivo. Boosting autophagy, either pharmacologically (with temsirolimus) or by dietary intervention (with trehalose), rescued the Δ9-tetrahydrocannabinol-induced impairment of motor coordination in mice. The combination of conditional knockout mouse models and viral vector-mediated autophagy-modulating strategies in vivo showed that cannabinoid CB1 receptors located on neurons belonging to the direct (striatonigral) pathway are required for the motor-impairing activity of Δ9-tetrahydrocannabinol by inhibiting local autophagy. Taken together, these findings identify inhibition of autophagy as an unprecedented mechanistic link between cannabinoids and motor performance, and suggest that activators of autophagy might be considered as potential therapeutic tools to treat specific cannabinoid-evoked behavioral alterations.
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Autofagia/efeitos dos fármacos , Canabinoides/farmacologia , Desempenho Psicomotor/efeitos dos fármacos , Putamen/fisiologia , Substância Negra/fisiologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Putamen/efeitos dos fármacos , Substância Negra/efeitos dos fármacosRESUMO
INTRODUCTION: one of the main extradigestive manifestations of celiac disease is the decrease in bone mineral density (BMD). Bone densitometry performed with DXA is the method of choice for BMD assessment. Indications for its use in celiac children are controversial. OBJECTIVE: analyzing BMD and various clinical-analytical variables in celiac children when diagnosed and after a gluten-free diet. Define a profile of patients who are more likely to present BMD involvement based on several individual characteristics, to perform DXA indications. METHODS: study performed in 24 celiac children (12 boys) (age: 8.7 ± 3.3 years). Their BMD was determined at diagnosis and after a gluten-free diet using DXA. The BMD was compared in each patient in the two moments of the study and at the moment of diagnosis between groups of patients stratified according to severity criteria dependent on clinical, analytical and histological variables. RESULTS: BMD was normal in all patients studied at the time of diagnosis and after treatment, with no difference between the two moments of the analysis. Children who presented symptomatology when diagnosed with celiac disease had lower spine and femur BMD than asymptomatic ones. The calcemia had an inverse correlation with the time of evolution of the disease before its diagnosis. CONCLUSIONS: in general, in our setting, the study of bone mineralization in celiac children is not indicated, unless there has been a prolonged clinical course before diagnosis.
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Densidade Óssea , Doença Celíaca/diagnóstico por imagem , Doença Celíaca/dietoterapia , Dieta Livre de Glúten , Absorciometria de Fóton , Criança , Pré-Escolar , Feminino , Fêmur/diagnóstico por imagem , Humanos , Estudos Longitudinais , Masculino , Coluna Vertebral/diagnóstico por imagemRESUMO
INTRODUCTION: In valgus knees of young patients, opening-wedge distal femoral osteotomy is a valid treatment option for axial corrections. It allows the surgeon to achieve accurate correction, which is directly related to the functional outcome and survivorship of the osteotomy. This study presents a new technique based on three-dimensional (3D)-printed cutting guides for opening-wedge distal femoral osteotomies, in which pre-operative planning and intraoperative executional accuracy play a major role. MATERIAL AND METHODS: Pursuing axial correction accuracy, 3D-printed patient-specific positioning guides and wedge spacers were both created and used by the surgeon to implement the femoral osteotomy. The proposed technique was performed in 12 consecutive patients (cases). The results were compared with 20 patients (controls) in which opening-wedge distal femoral osteotomies were performed following the traditional technique. Accuracy of the axial correction, surgical time, fluoroscopic time and costs were measured. RESULTS: More accurate axial correction with reduced surgical time (32min less), intraoperative fluoroscopic images (59 images less) and costs (estimated 412 less) were achieved with the use of the customized guides when compared with the traditional technique. DISCUSSION: Accurate correction of the axial alignment of the limb is a critical step in survivorship of the osteotomy. Improving the technique to enhance accuracy focused on this issue. CONCLUSIONS: The use of patient-customized cutting guides minimised human error; therefore, surgical time was reduced and accurate axial correction was achieved. The surgeon mastered all steps in a do-it-yourself philosophy style.
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Fêmur/cirurgia , Osteotomia/instrumentação , Impressão Tridimensional , Adulto , Estudos de Casos e Controles , Redução de Custos , Feminino , Fluoroscopia/estatística & dados numéricos , Humanos , Masculino , Duração da Cirurgia , Osteoartrite do Joelho/cirurgia , Cuidados Pré-OperatóriosRESUMO
BACKGROUND AND AIM: The first-degree relatives (FDRs) of patients with coeliac disease are the main risk group for disease development. The study aims to evaluate the screening strategy in FDRs with negative coeliac serology based on human leukocyte antigen (HLA) genotyping, followed by duodenal biopsy, and to analyze the prevalence of gastrointestinal symptoms and the influence of gluten intake. METHODS: Adult FDRs with negative coeliac serology were invited to participate (n = 205), and a total of 139 completed the study protocol. HLA genotyping, transglutaminase antibody assessment, and duodenal biopsy were performed. Symptomatology was assessed using questionnaires during the various phases of dietary modification (baseline diet, gluten-free diet, and gluten overload). RESULTS: The study included 139 participants (mean age, 42 years; 53.2% women). HLA-DQ2/8 was positive in 78.4% of the participants (homozygous, 15.1%; heterozygous, 63.3%). Histopathological alterations were noted in 37.1% of participants who underwent duodenal biopsy (Marsh I, 32.7%; Marsh IIIa, 4.4%). At baseline, symptoms were observed in 45.7% of the participants, and the proportion decreased to 24.5% after the gluten-free diet (P < 0.001). Symptoms were not associated with the presence of histological alterations or genetic risk. However, younger age (odds ratio [OR] = 0.91), female sex (OR = 2.9), and the presence of autoimmune disorders (OR = 2.8) were independently associated with a significant symptom response to the gluten-free diet. CONCLUSIONS: Duodenal lymphocytosis and atrophy are frequently noted in FDRs, despite negative serological markers. In addition, gastrointestinal symptoms are commonly present and associated with gluten intake regardless of the histological pathology.