Polytomous Rasch Analyses of Surgeons' Decision-Making on Choice of Procedure in Endoscopic Lumbar Spinal Stenosis Decompression Surgeries.

BACKGROUND: With the growing prevalence of lumbar spinal stenosis, endoscopic surgery, which incorporates techniques such as transforaminal, interlaminar, and unilateral biportal (UBE) endoscopy, is increasingly considered. However, the patient selection criteria are debated among spine surgeons. OBJECTIVE: This study used a polytomous Rasch analysis to evaluate the factors influencing surgeon decision-making in selecting patients for endoscopic surgical treatment of lumbar spinal stenosis. METHODS: A comprehensive survey was distributed to a representative sample of 296 spine surgeons. Questions encompassed various patient-related and clinical factors, and responses were captured on a logit scale graphically displaying person-item maps and category probability curves for each test item. Using a Rasch analysis, the data were subsequently analyzed to determine the latent traits influencing decision-making. RESULTS: The Rasch analysis revealed that surgeons' preferences for transforaminal, interlaminar, and UBE techniques were easily influenced by comfort level and experience with the endoscopic procedure and patient-related factors. Harder-to-agree items included technological aspects, favorable clinical outcomes, and postoperative functional recovery and rehabilitation. Descriptive statistics suggested interlaminar as the best endoscopic spinal stenosis decompression technique. However, logit person-item analysis integral to the Rasch methodology showed highest intensity for transforaminal followed by interlaminar endoscopic lumbar stenosis decompression. The UBE technique was the hardest to agree on with a disordered person-item analysis and thresholds in category probability curve plots. CONCLUSION: Surgeon decision-making in selecting patients for endoscopic surgery for lumbar spinal stenosis is multifaceted. While the framework of clinical guidelines remains paramount, on-the-ground experience-based factors significantly influence surgeons' selection of patients for endoscopic lumbar spinal stenosis surgeries. The Rasch methodology allows for a more granular psychometric evaluation of surgeon decision-making and accounts better for years-long experience that may be lost in standardized clinical guideline development. This new approach to assessing spine surgeons' thought processes may improve the implementation of evidence-based protocol change dictated by technological advances was endorsed by the Interamerican Society for Minimally Invasive Spine Surgery (SICCMI), the International Society for Minimal Intervention in Spinal Surgery (ISMISS), the Mexican Spine Society (AMCICO), the Brazilian Spine Society (SBC), the Society for Minimally Invasive Spine Surgery (SMISS), the Korean Minimally Invasive Spine Society (KOMISS), and the International Society for the Advancement of Spine Surgery (ISASS).

Sjögren: unique surname, two men, four syndromes and one disease.

Henrik and Torsten Sjögren (/'ʃoʊɡrən/ or SHOH-grən) were two Swedish physicians living in the same period, but completely unrelated, except for their notable contributions to Medicine. The first one described keratoconjunctivitis sicca, afterward called Sjögren's syndrome, and a fishing net aspect retinal pigmentation affecting visual acuity, nowadays known as Sjögren reticular dystrophy. The last one contributed to the understanding of Spielmeyer-Sjögren disease, Marinesco-Sjögren, and Sjögren-Larsson syndromes, all related to genetic disorders and neurological symptoms. In this paper, we aim to describe each disorder, in order to avoid any misunderstanding in diagnosis and for historical record.

Henrik e Torsten Sjögren (/ˈʃoʊɡrən/ ou SHOH-grən) foram dois médicos suecos que viveram na mesma época, mas não tinham nenhuma relação entre si, exceto por suas notáveis contribuições à medicina. O primeiro descreveu a ceratoconjuntivite sicca, posteriormente chamada de síndrome de Sjögren, e uma pigmentação da retina com aspecto de rede de pesca que afeta a acuidade visual, hoje conhecida como distrofia reticular de Sjögren. O último contribuiu para a compreensão da doença de Spielmeyer-Sjögren, das síndromes de Marinesco-Sjögren e Sjögren-Larsson, todas relacionadas a distúrbios genéticos e sintomas neurológicos. Neste artigo, pretendemos descrever cada desordem, a fim de evitar qualquer mal-entendido no diagnóstico e para registro histórico.

New-onset diabetes after kidney transplantation: Assessing urinary Wilm's tumor-1 protein to predict renal allograft dysfunction.

PURPOSE: New-onset diabetes after transplantation (NODAT) is a frequent metabolic complication associated with podocyte damage and renal allograft dysfunction. Thus, Wilm's tumor-1 (WT-1) protein, as a podocyte marker, holds promise as an option to evaluate renal allograft dysfunction in NODAT. Therefore, the study aimed to investigate urinary WT-1 levels in NODAT patients during the first year after kidney transplantation (KTx). MATERIALS AND METHODS: KTx patients were categorized into non-NODAT and NODAT groups. Fasting blood glucose, glycated hemoglobin (HbA1c), urinary albumin/creatinine ratio (ACR), serum creatinine, estimated glomerular filtration rate (eGFR), and urinary WT-1 were measured at 3, 6, 9, and 12-months post-KTx. RESULTS: The NODAT group manifested elevated levels of blood glucose and HbA1c during the first year post-KTx. Also, exhibited elevations in ACR and serum creatinine levels at 6, 9, and 12-months post-KTx when compared to non-NODAT group. Conversely, eGFR values in the NODAT group demonstrated significant declines at 3, 6, and 9-months post-KTx relative to non-NODAT. Furthermore, NODAT group exhibited a median annual eGFR of 47 â€‹mL/min/1.73 â€‹m2. Urinary WT-1 levels at 3, 6, 9, and 12-months post-KTx were significantly higher in the NODAT group compared to non-NODAT. Additionally, noteworthy positive correlations were identified between urinary WT-1 and HbA1c levels, along with significant negative correlations between urinary WT-1 and eGFR at the 3, 6, 9, and 12-months post-KTx. CONCLUSION: The increased urinary WT-1 levels from 3-months post-KTx in NODAT patients may indicate the first sign of podocyte injury, predicting a renal allograft dysfunction in these patients.

4'-fluorocannabidiol associated with capsazepine restrains L-DOPA-induced dyskinesia in hemiparkinsonian mice: Contribution of anti-inflammatory and anti-glutamatergic mechanisms.

We tested the efficacy of 4'-fluorocannabidiol (4'-F-CBD), a semisynthetic cannabidiol derivative, and HU-910, a cannabinoid receptor 2 (CB2) agonist in resolving l-DOPA-induced dyskinesia (LID). Specifically, we were interested in studying whether these compounds could restrain striatal inflammatory responses and rescue glutamatergic disturbances characteristic of the dyskinetic state. C57BL/6 mice were rendered hemiparkinsonian by unilateral striatal lesioning with 6-OHDA. Abnormal involuntary movements were then induced by repeated i.p. injections of l-DOPA + benserazide. After LID was installed, the effects of a 3-day treatment with 4'-F-CBD or HU-910 in combination or not with the TRPV1 antagonist capsazepine (CPZ) or CB2 agonists HU-308 and JWH015 were assessed. Immunostaining was conducted to investigate the impacts of 4'-F-CBD and HU-910 (with CPZ) on inflammation and glutamatergic synapses. Our results showed that the combination of 4'-F-CBD + CPZ, but not when administered alone, decreased LID. Neither HU-910 alone nor HU-910+CPZ were effective. The CB2 agonists HU-308 and JWH015 were also ineffective in decreasing LID. Both combination treatments efficiently reduced microglial and astrocyte activation in the dorsal striatum of dyskinetic mice. However, only 4'-F-CBD + CPZ normalized the density of glutamate vesicular transporter-1 (vGluT1) puncta colocalized with the postsynaptic density marker PSD95. These findings suggest that 4'-F-CBD + CPZ normalizes dysregulated cortico-striatal glutamatergic inputs, which could be involved in their anti-dyskinetic effects. Although it is not possible to rule out the involvement of anti-inflammatory mechanisms, the decrease in striatal neuroinflammation markers by 4'-F-CBD and HU-910 without an associated reduction in LID indicates that they are insufficient per se to prevent LID manifestations.

Cannabidiol and it fluorinate analog PECS-101 reduces hyperalgesia and allodynia in trigeminal neuralgia via TRPV1 receptors.

Trigeminal neuralgia (TN) is an intense and debilitating orofacial pain. The gold standard treatment for TN is carbamazepine. This antiepileptic drug provides pain relief with limited efficacy and side effects. To study the antinociceptive potential of cannabidiol (CBD) and its fluorinated analog PECS-101 (former HUF-101), we induced unilateral chronic constriction injury of the infraorbital nerve (IoN-CCI) in male Wistar rats. Seven days of treatment with CBD (30 mg/kg), PECS-101 (3, 10, and 30 mg/kg), or carbamazepine (10 and 30 mg/kg) reduced allodynia and hyperalgesia responses. Unlike carbamazepine, CBD and PECS-101 did not impair motor activity. The relief of the hypersensitive reactions has been associated with transient receptor potential vanilloid type 1 (TRPV1) modulation in the trigeminal spinal nucleus. CBD (30 mg/kg) and PECS-101 (10 and 30 mg/kg) reversed the increased expression of TRPV1 induced by IoN-CCI in this nucleus. Using a pharmacological strategy, the combination of the selective TRPV1 antagonist (capsazepine-CPZ - 5 mg/kg) with sub-effective doses of CBD (3 and 10 mg/kg) is also able to reverse the IoN-CCI-induced allodynia and hyperalgesia responses. This effect was accompanied by reduced TRPV1 protein expression in the trigeminal spinal nucleus. Our results suggest that CBD and PECS-101 may benefit trigeminal neuralgia without motor coordination impairments. PECS-101 is more potent against the hypernociceptive and motor impairment induced by TN compared to CBD and carbamazepine. The antinociceptive effect of these cannabinoids is partially mediated by TRPV1 receptors in the caudal part of the trigeminal spinal nucleus, the first central station of orofacial pain processing.

The two synthetic cannabinoid compounds 4'-F-CBD and HU-910 efficiently restrain inflammatory responses of brain microglia and astrocytes.

To study the anti-inflammatory potential of the two synthetic cannabinoids 4'-F-CBD and HU-910, we used post-natal brain cultures of mouse microglial cells and astrocytes activated by reference inflammogens. We found that 4'-F-CBD and HU-910 efficiently curtailed the release of TNF-α, IL-6, and IL-1ß in microglia and astrocytes activated by the bacterial Toll-Like Receptor (TLR)4 ligand LPS. Upon LPS challenge, 4'-F-CBD and HU-910 also prevented the activation of phenotypic activation markers specific to microglia and astrocytes, that is, Iba-1 and GFAP, respectively. In microglial cells, the two test compounds also efficiently restrained LPS-stimulated release of glutamate, a non-cytokine inflammation marker for these cells. The immunosuppressive effects of the two cannabinoid compounds were concentration-dependent and observable between 1 and 10 µM. These effects were not dependent on cannabinoid or cannabinoid-like receptors. Both 4'-F-CBD and HU-910 were also capable of restraining the inflammogenic activity of Pam3CSK4, a lipopeptide that activates TLR2, and of BzATP, a prototypic agonist of P2X7 purinergic receptors, suggesting that these two cannabinoids could exert immunosuppressive effects against a variety of inflammatory stimuli. Using LPS-stimulated microglia and astrocytes, we established that the immunosuppressive action of 4'-F-CBD and HU-910 resulted from the inhibition of ROS produced by NADPH oxidase and subsequent repression of NF-κB-dependent signaling events. Our results suggest that 4'-F-CBD and HU-910 may have therapeutic utility in pathological conditions where neuroinflammatory processes are prominent.

Evaluation and monitoring of eye findings in children exposed to Zika virus during gestation: 3 years of follow-up.

INTRODUCTION: Congenital Zika syndrome (CZS) is a recently described disease. Our main objective was to evaluate and monitor, over 3 years, the ophthalmoscopic findings in children exposed to zika virus (ZIKV) during gestation. METHODS: This prospective observational study was conducted in Rio de Janeiro, Brazil, between April 2016 and May 2019. We evaluated two groups with exanthema serving as a proxy for viremia: (i) children whose mothers had exanthema during pregnancy and (ii) children who had microcephaly without maternal exanthema during pregnancy. We performed indirect ophthalmoscopy at recruitment and every 6 months thereafter. We also tested the association between ocular findings with maternal exanthema, microcephaly, CZS and maternal infection confirmed by reverse transcriptase quantitative polymerase chain reaction and gender. RESULTS: Of the 72 children included, 16 (22.2%) had optic nerve and/or retinal lesions. All 16 had CZS and 15 (93.7%) had microcephaly (14 at birth and 1 postnatally). The child with postnatally acquired microcephaly was born to a mother without exanthema during pregnancy. Fifty-six (77.8%) of the 72 children were followed for a median time of 24 months and none exhibited differences between admission and follow-up examinations. After logistic regression, only microcephaly at birth was associated with eye abnormalities (odds ratio, 77.015; 95% confidence interval, 8.85-670.38; p < 0.001). CONCLUSION: We observed that there was no progression of the lesions over the follow-up period. We also showed that the eye findings were associated only with microcephaly at birth. Attention should be paid to all children born during a ZIKV epidemic, regardless of maternal exanthema and/or microcephaly at birth.

Anatomical Implications of Chiari I and Basilar Invagination (Type B) in the IV Ventricle and Cisterna Magna.

OBJECTIVE: To analyze the anatomical changes of the IV ventricle and cisterna magna in the Chiari malformation I (CMI) and basilar invagination (type B). METHODS: This is a controlled study with 161 exams of magnetic resonance imaging (MRI) of adults grouped into control (n = 37), basilar invagination (BI; n = 31), Chiari malformation I (CMI; n = 37), and CMI+BI (n = 56). The MRIs were analyzed using the visualization software Osirix (Pixmeo, Bernex, Geneva, version 3.8.2). The morphometric variables were: distance from the obex to the McRae line; length of the IV ventricle floor; and the area and volume of the cisterna magna. The univariate ANOVA followed by Tukey's post-hoc test was applied to evaluate the difference between the groups. The difference between sexes was evaluated by the t test for each group. RESULTS: Alterations in the cisterna magna and IV ventricle were more evident only in the CMI and CMI+BI groups. For both sexes, the CMI and CMI+BI groups showed: a reduction in the CSF space (P < 0.001), cisterna magna with volume reduction (P < 0.001), low position of the obex (P < 0.001), and IV ventricle more elongated (male P = 0.007 and female P < 0.001). The BI group had no significant change in the analysis by sex. CONCLUSIONS: The CMI (isolated and associated with BI) showed a low obex position and elongation of the IV ventricle due to traction towards the spinal canal. The reduction of cisterna magna volume added to the occupation of the cerebellar tonsils can impact in the cerebrospinal fluid dynamics. The BI when isolated was not related to alterations in the parameters of cerebrospinal fluid spaces studied.

Randomized Clinical Trials and Observational Tribulations: Providing Clinical Evidence for Personalized Surgical Pain Management Care Models.

Proving clinical superiority of personalized care models in interventional and surgical pain management is challenging. The apparent difficulties may arise from the inability to standardize complex surgical procedures that often involve multiple steps. Ensuring the surgery is performed the same way every time is nearly impossible. Confounding factors, such as the variability of the patient population and selection bias regarding comorbidities and anatomical variations are also difficult to control for. Small sample sizes in study groups comparing iterations of a surgical protocol may amplify bias. It is essentially impossible to conceal the surgical treatment from the surgeon and the operating team. Restrictive inclusion and exclusion criteria may distort the study population to no longer reflect patients seen in daily practice. Hindsight bias is introduced by the inability to effectively blind patient group allocation, which affects clinical result interpretation, particularly if the outcome is already known to the investigators when the outcome analysis is performed (often a long time after the intervention). Randomization is equally problematic, as many patients want to avoid being randomly assigned to a study group, particularly if they perceive their surgeon to be unsure of which treatment will likely render the best clinical outcome for them. Ethical concerns may also exist if the study involves additional and unnecessary risks. Lastly, surgical trials are costly, especially if the tested interventions are complex and require long-term follow-up to assess their benefit. Traditional clinical testing of personalized surgical pain management treatments may be more challenging because individualized solutions tailored to each patient's pain generator can vary extensively. However, high-grade evidence is needed to prompt a protocol change and break with traditional image-based criteria for treatment. In this article, the authors review issues in surgical trials and offer practical solutions.

The Changing Environment in Postgraduate Education in Orthopedic Surgery and Neurosurgery and Its Impact on Technology-Driven Targeted Interventional and Surgical Pain Management: Perspectives from Europe, Latin America, Asia, and The United States.

Personalized care models are dominating modern medicine. These models are rooted in teaching future physicians the skill set to keep up with innovation. In orthopedic surgery and neurosurgery, education is increasingly influenced by augmented reality, simulation, navigation, robotics, and in some cases, artificial intelligence. The postpandemic learning environment has also changed, emphasizing online learning and skill- and competency-based teaching models incorporating clinical and bench-top research. Attempts to improve work-life balance and minimize physician burnout have led to work-hour restrictions in postgraduate training programs. These restrictions have made it particularly challenging for orthopedic and neurosurgery residents to acquire the knowledge and skill set to meet the requirements for certification. The fast-paced flow of information and the rapid implementation of innovation require higher efficiencies in the modern postgraduate training environment. However, what is taught typically lags several years behind. Examples include minimally invasive tissue-sparing techniques through tubular small-bladed retractor systems, robotic and navigation, endoscopic, patient-specific implants made possible by advances in imaging technology and 3D printing, and regenerative strategies. Currently, the traditional roles of mentee and mentor are being redefined. The future orthopedic surgeons and neurosurgeons involved in personalized surgical pain management will need to be versed in several disciplines ranging from bioengineering, basic research, computer, social and health sciences, clinical study, trial design, public health policy development, and economic accountability. Solutions to the fast-paced innovation cycle in orthopedic surgery and neurosurgery include adaptive learning skills to seize opportunities for innovation with execution and implementation by facilitating translational research and clinical program development across traditional boundaries between clinical and nonclinical specialties. Preparing the future generation of surgeons to have the aptitude to keep up with the rapid technological advances is challenging for postgraduate residency programs and accreditation agencies. However, implementing clinical protocol change when the entrepreneur-investigator surgeon substantiates it with high-grade clinical evidence is at the heart of personalized surgical pain management.

Vitamin D status and biomarkers of renal graft function after kidney transplantation: a longitudinal study / Estado de la vitamina D y biomarcadores de función del injerto renal después del trasplante de riñón: un estudio longitudinal

Introduction: Low 25-hydroxyvitamin D [25(OH)D] levels occur after kidney transplantation (KTx), and can be associated with increase the risk of graft loss. This longitudinal study aimed to evaluate the vitamin D status and association with biomarkers of the renal graft function after KTx. Methods: this longitudinal study included 42 patients evaluated at baseline, 3 and 6 months after KTx. Biodemographic, clinical, and biochemical parameters such as 25(OH)D and parathyroid hormone (PTH), and biomarkers of renal graft function, such as creatinine, estimated glomerular filtration rate (eGFR), and albumin/creatinine ratio (ACR), were assessed. Sun exposure was also evaluated. Patients were categorized according to their 25(OH)D levels. Results: at baseline, 25(OH)D levels < 30 ng/mL were found in 43 % patients, and 38 % of these patients failed to improve their 25(OH)D levels by 6 months after KTx. Low 25(OH)D levels occurred regardless of sun exposure. Further, 44 % patients developed albuminuria at 6 months. An increased ACR was observed in patients with 25(OH)D levels < 30 ng/mL (p = 0.002) compared to that in patients with 25(OH)D > 30 ng/mL. Additionally, 25(OH)D levels were negatively correlated with ACR at 6 months post-KTx (r = -0.444; p = 0.003). Twelve (28.6 %) patients with 25(OH)D levels < 30 ng/mL showed no eGFR recovery until 6 months after KTx. Conclusion: low vitamin D levels and increased albuminuria were observed at 6 months after KTx, even in a region with high sun exposure. The association between vitamin D status and biomarkers of renal graft function after KTx should be explored in further studies. (AU)

Introducción: los bajos niveles de 25-hidroxivitamina D [25(OH)D] ocurren después del procedimiento de trasplante de riñón (KTx) y pueden estar asociados con un aumento del riesgo de pérdida del injerto. Este estudio longitudinal tuvo como objetivo evaluar el estado de la vitamina D y la asociación con los biomarcadores de función del injerto renal después del KTx. Métodos: este estudio longitudinal incluyó a 42 pacientes que fueron evaluados al inicio del estudio, y 3 y 6 meses después del KTx. Se evaluaron los parámetros biodemográficos, clínicos y bioquímicos, como 25(OH)D y hormona paratiroidea (PTH), y los biomarcadores de función del injerto renal, como creatinina, tasa de filtración glomerular estimada (eGFR) y relación albúmina/creatinina (ACR). También se evaluó la exposición al sol. Los pacientes se clasificaron según sus niveles de 25(OH)D. Resultados: al inicio del estudio se encontraron niveles de 25(OH)D < 30 ng/ml en el 43 % de los pacientes, mientras que el 38 % de estos pacientes no lograron mejorar sus niveles de 25(OH)D a los 6 meses después del KTx. También se produjeron niveles bajos de 25(OH)D independientemente de la exposición al sol. Asimismo, el 44 % de los pacientes desarrollaron albuminuria a los 6 meses. Se observó un aumento de la ACR en los pacientes con niveles de 25(OH)D < 30 ng/mL (p = 0,002) en comparación con los pacientes con 25(OH)D > 30 ng/mL. Además,los niveles de 25(OH)D se correlacionaron negativamente con la ACR a los 6 meses después del KTx (r = -0,444; p = 0,003). Doce (28,6 %) pacientes con niveles de 25(OH)D < 30 ng/ml no mostraron recuperación de la TFGe hasta 6 meses después del KTx. Conclusión: se observaron niveles bajos de vitamina D y un aumento de la albuminuria a los 6 meses después del KTx, incluso en una región con alta exposición solar. La asociación entre el estado de la vitamina D y los biomarcadores de función del injerto renal después del KTx debeexplorarse en estudios adicionales. (AU)

Rescue of Dopamine Neurons from Iron-Dependent Ferroptosis by Doxycycline and Demeclocycline and Their Non-Antibiotic Derivatives.

Several studies have reported that the tetracycline (TC) class antibiotic doxycycline (DOX) is effective against Parkinson's disease (PD) pathomechanisms. The aim of the present work was three-fold: (i) Establish a model system to better characterize neuroprotection by DOX; (ii) Compare the rescue effect of DOX to that of other TC antibiotics; (iii) Discover novel neuroprotective TCs having reduced antibiotic activity. For that, we used cultures of mouse midbrain dopamine (DA) neurons and experimental conditions that model iron-mediated oxidative damage, a key mechanism in PD pathobiology. We found that DOX and the other TC antibiotic, demeclocycline (DMC), provided sustained protection to DA neurons enduring iron-mediated insults, whereas chlortetracycline and non-TC class antibiotics did not. Most interestingly, non-antibiotic derivatives of DOX and DMC, i.e., DDOX and DDMC, respectively, were also robustly protective for DA neurons. Interestingly, DOX, DDOX, DMC, and DDMC remained protective for DA neurons until advanced stages of neurodegeneration, and the rescue effects of TCs were observable regardless of the degree of maturity of midbrain cultures. Live imaging studies with the fluorogenic probes DHR-123 and TMRM revealed that protective TCs operated by preventing intracellular oxidative stress and mitochondrial membrane depolarization, i.e., cellular perturbations occurring in this model system as the ultimate consequence of ferroptosis-mediated lipid peroxidation. If oxidative/mitochondrial insults were generated acutely, DOX, DDOX, DMC, and DDMC were no longer neuroprotective, suggesting that these compounds are mostly effective when neuronal damage is chronic and of low-intensity. Overall, our data suggest that TC derivatives, particularly those lacking antibiotic activity, might be of potential therapeutic utility to combat low-level oxidative insults that develop chronically in the course of PD neurodegeneration.

Vitamin D status and biomarkers of renal graft function after kidney transplantation: a longitudinal study.

Introduction: Introduction: Low 25-hydroxyvitamin D [25(OH)D] levels occur after kidney transplantation (KTx), and can be associated with increase the risk of graft loss. This longitudinal study aimed to evaluate the vitamin D status and association with biomarkers of the renal graft function after KTx. Methods: this longitudinal study included 42 patients evaluated at baseline, 3 and 6 months after KTx. Biodemographic, clinical, and biochemical parameters such as 25(OH)D and parathyroid hormone (PTH), and biomarkers of renal graft function, such as creatinine, estimated glomerular filtration rate (eGFR), and albumin/creatinine ratio (ACR), were assessed. Sun exposure was also evaluated. Patients were categorized according to their 25(OH)D levels. Results: at baseline, 25(OH)D levels < 30 ng/mL were found in 43 % patients, and 38 % of these patients failed to improve their 25(OH)D levels by 6 months after KTx. Low 25(OH)D levels occurred regardless of sun exposure. Further, 44 % patients developed albuminuria at 6 months. An increased ACR was observed in patients with 25(OH)D levels < 30 ng/mL (p = 0.002) compared to that in patients with 25(OH)D > 30 ng/mL. Additionally, 25(OH)D levels were negatively correlated with ACR at 6 months post-KTx (r = -0.444; p = 0.003). Twelve (28.6 %) patients with 25(OH)D levels < 30 ng/mL showed no eGFR recovery until 6 months after KTx. Conclusion: low vitamin D levels and increased albuminuria were observed at 6 months after KTx, even in a region with high sun exposure. The association between vitamin D status and biomarkers of renal graft function after KTx should be explored in further studies.

Introducción: Introducción: los bajos niveles de 25-hidroxivitamina D [25(OH)D] ocurren después del procedimiento de trasplante de riñón (KTx) y pueden estar asociados con un aumento del riesgo de pérdida del injerto. Este estudio longitudinal tuvo como objetivo evaluar el estado de la vitamina D y la asociación con los biomarcadores de función del injerto renal después del KTx. Métodos: este estudio longitudinal incluyó a 42 pacientes que fueron evaluados al inicio del estudio y, 3 y 6 meses después del KTx. Se evaluaron los parámetros biodemográficos, clínicos y bioquímicos, como 25(OH)D y hormona paratiroidea (PTH), y los biomarcadores de función del injerto renal, como creatinina, tasa de filtración glomerular estimada (eGFR) y relación albúmina/creatinina (ACR). También se evaluó la exposición al sol. Los pacientes se clasificaron según sus niveles de 25(OH)D. Resultados: al inicio del estudio se encontraron niveles de 25(OH)D < 30 ng/ml en el 43 % de los pacientes, mientras que el 38 % de estos pacientes no lograron mejorar sus niveles de 25(OH)D a los 6 meses después del KTx. También se produjeron niveles bajos de 25(OH)D independientemente de la exposición al sol. Asimismo, el 44 % de los pacientes desarrollaron albuminuria a los 6 meses. Se observó un aumento de la ACR en los pacientes con niveles de 25(OH)D < 30 ng/mL (p = 0,002) en comparación con los pacientes con 25(OH)D > 30 ng/mL. Además, los niveles de 25(OH)D se correlacionaron negativamente con la ACR a los 6 meses después del KTx (r = -0,444; p = 0,003). Doce (28,6 %) pacientes con niveles de 25(OH)D < 30 ng/ml no mostraron recuperación de la TFGe hasta 6 meses después del KTx. Conclusión: se observaron niveles bajos de vitamina D y un aumento de la albuminuria a los 6 meses después del KTx, incluso en una región con alta exposición solar. La asociación entre el estado de la vitamina D y los biomarcadores de función del injerto renal después del KTx debe explorarse en estudios adicionales.

Doxycycline attenuates l-DOPA-induced dyskinesia through an anti-inflammatory effect in a hemiparkinsonian mouse model.

The pharmacological manipulation of neuroinflammation appears to be a promising strategy to alleviate l-DOPA-induced dyskinesia (LID) in Parkinson's disease (PD). Doxycycline (Doxy), a semisynthetic brain-penetrant tetracycline antibiotic having interesting anti-inflammatory properties, we addressed the possibility that this compound could resolve LID in l-DOPA-treated C57BL/6 mice presenting either moderate or intermediate lesions of the mesostriatal dopaminergic pathway generated by intrastriatal injections of 6-OHDA. Doxy, when given subcutaneously before l-DOPA at doses of 20 mg kg-1 and 40 mg kg-1, led to significant LID reduction in mice with moderate and intermediate dopaminergic lesions, respectively. Importantly, Doxy did not reduce locomotor activity improved by l-DOPA. To address the molecular mechanism of Doxy, we sacrificed mice with mild lesions 1) to perform the immunodetection of tyrosine hydroxylase (TH) and Fos-B and 2) to evaluate a panel of inflammation markers in the striatum, such as cyclooxygenase-2 and its downstream product Prostaglandin E2 along with the cytokines TNF-α, IL-1ß and IL-6. TH-immunodetection revealed that vehicle and Doxy-treated mice had similar striatal lesions, excluding that LID improvement by Doxy could result from neurorestorative effects. Importantly, LID inhibition by Doxy was associated with decreased Fos-B and COX-2 expression and reduced levels of PGE2, TNF-α, and IL-1ß in the dorsolateral striatum of dyskinetic mice. We conclude 1) that Doxy has the potential to prevent LID regardless of the intensity of dopaminergic lesioning and 2) that the anti-inflammatory effects of Doxy probably account for LID attenuation. Overall, the present results further indicate that Doxy might represent an attractive and alternative treatment for LID in PD.

Physics-Informed Data-Driven Prediction of 2D Normal Strain Field in Concrete Structures.

Concrete exhibits time-dependent long-term behavior driven by creep and shrinkage. These rheological effects are difficult to predict due to their stochastic nature and dependence on loading history. Existing empirical models used to predict rheological effects are fitted to databases composed largely of laboratory tests of limited time span and that do not capture differential rheological effects. A numerical model is typically required for application of empirical constitutive models to real structures. Notwithstanding this, the optimal parameters for the laboratory databases are not necessarily ideal for a specific structure. Data-driven approaches using structural health monitoring data have shown promise towards accurate prediction of long-term time-dependent behavior in concrete structures, but current approaches require different model parameters for each sensor and do not leverage geometry and loading. In this work, a physics-informed data-driven approach for long-term prediction of 2D normal strain field in prestressed concrete structures is introduced. The method employs a simplified analytical model of the structure, a data-driven model for prediction of the temperature field, and embedding of neural networks into rheological time-functions. In contrast to previous approaches, the model is trained on multiple sensors at once and enables the estimation of the strain evolution at any point of interest in the longitudinal section of the structure, capturing differential rheological effects.

Effects of an individualized nutritional intervention on kidney function, body composition, and quality of life in kidney transplant recipients: Study protocol for a randomized clinical trial.

BACKGROUND: Proteinuria after kidney transplantation (KTx) has been a frequent problem due to several factors, high protein intake being one of them. Individualized nutritional intervention in the late post-KTx period can promote the improvement or the reduction of risks associated with the parameters of evaluation of kidney function, body composition, and quality of life in individuals submitted to KTx. METHODS: This is a single-center, randomized and stratified clinical trial. The study will be conducted in a university hospital in northeastern Brazil with 174 individuals aged ≥19 years submitted to KTx and followed up for 12 months. Assessments will take place at 3-month intervals (T0, T3, T6, T9, and T12). The patients will be allocated to intervention and control groups by random allocation. The intervention group will receive individualized nutritional interventions with normoproteic diets (1.0 g/kg) after 60 days of KTx whereas the controls will receive the standard nutritional guidance for the post-KTx period. The primary efficacy variable is the change from baseline in log proteinuria assessed with the urinary albumin/creatinine ratio. Secondary efficacy variables include body composition, anthropometry, quality of life assessment and physical activity, lipid profile and glycemic control. Ninety-two subjects per group will afford 70% power to detect a difference of 25% between groups in log proteinuria. Primary efficacy analysis will be on the modified intention-to-treat population with between-groups comparison of the change from baseline in log proteinuria by analysis of covariance. DISCUSSION: The study will assess the effects of an individualized nutritional intervention on proteinuria 12 months after KTx. TRIAL REGISTRATION: REBEC (RBR-8XBQK5).

Oropharyngeal colostrum immunotherapy and nutrition in preterm newborns: meta-analysis.

OBJECTIVE: To investigated the effect of oropharyngeal colostrum immunotherapy in reducing the time required for very low birth weight preterm newborns (VLBW-PTNB: < 1,500g and < 37 weeks) to achieve full enteral nutrition. METHODS: Literature search was conducted using four databases, including gray literature, with additional manual search of the references of selected articles. Eligibility criteria consisted of randomized clinical trials, without restriction regarding the date or language of the publication. Two independent reviewers performed the article selection and data extraction. The random-effects meta-analysis used a non-standard technique to assess the mean difference in days to achieve full enteral nutrition, carried out by the Stata 15 statistic program. RESULTS: The systematic review comprised 10 studies, and five were selected for meta-analysis, with a population of 764 VLBW-PTNB and gestational age of birth between 25 and 32 weeks. The studies were conducted between 2011 and 2018 in North America, Asia and Africa, with only one conducted in South America. Altogether, they reported the number of days it took 708 VLBW-PTNB to achieve full enteral nutrition, with newborns treated with immunotherapy showing a shorter time in only three studies. Meta-analysis showed a mean difference of -4.26 days, (95% CI -7.44; -1.08d), with high heterogeneity (I2 = 83.1%). CONCLUSION: The use of oropharyngeal colostrum immunotherapy can reduce the time for VLBW-PTNB to achieve full nutrition when compared to those who used a placebo or received routine care.