Turn-table micro-CT scanner for dynamic perfusion imaging in mice: design, implementation, and evaluation.

Objective.This study introduces a novel desktop micro-CT scanner designed for dynamic perfusion imaging in mice, aimed at enhancing preclinical imaging capabilities with high resolution and low radiation doses.Approach.The micro-CT system features a custom-built rotating table capable of both circular and helical scans, enabled by a small-bore slip ring for continuous rotation. Images were reconstructed with a temporal resolution of 3.125 s and an isotropic voxel size of 65µm, with potential for higher resolution scanning. The system's static performance was validated using standard quality assurance phantoms. Dynamic performance was assessed with a custom 3D-bioprinted tissue-mimetic phantom simulating single-compartment vascular flow. Flow measurements ranged from 1.51to 9 ml min-1, with perfusion metrics such as time-to-peak, mean transit time, and blood flow index calculated.In vivoexperiments involved mice with different genetic risk factors for Alzheimer's and cardiovascular diseases to showcase the system's capabilities for perfusion imaging.Main Results.The static performance validation confirmed that the system meets standard quality metrics, such as spatial resolution and uniformity. The dynamic evaluation with the 3D-bioprinted phantom demonstrated linearity in hemodynamic flow measurements and effective quantification of perfusion metrics.In vivoexperiments highlighted the system's potential to capture detailed perfusion maps of the brain, lungs, and kidneys. The observed differences in perfusion characteristics between genotypic mice illustrated the system's capability to detect physiological variations, though the small sample size precludes definitive conclusions.Significance.The turn-table micro-CT system represents a significant advancement in preclinical imaging, providing high-resolution, low-dose dynamic imaging for a range of biological and medical research applications. Future work will focus on improving temporal resolution, expanding spectral capabilities, and integrating deep learning techniques for enhanced image reconstruction and analysis.

Human gut microbiota analysis of cystic fibrosis infants using metaproteomics.

We report a metaproteomic analysis of the gut microbiota of eight infants with cystic fibrosis, during the first year of life. This is the first study in this disease that uses metaproteomics to analyze stool samples from patients at such a young age.

N-Glycan profile of the cell membrane as a probe for lipopolysaccharide-induced microglial neuroinflammation uncovers the effects of common fatty acid supplementation.

Altered N-glycosylation of proteins on the cell membrane is associated with several neurodegenerative diseases. Microglia are an ideal model for studying glycosylation and neuroinflammation, but whether aberrant N-glycosylation in microglia can be restored by diet remains unknown. Herein, we profiled the N-glycome, proteome, and glycoproteome of the human microglia following lipopolysaccharide (LPS) induction to probe the impact of dietary and gut microbe-derived fatty acids-oleic acid, lauric acid, palmitic acid, valeric acid, butyric acid, isobutyric acid, and propionic acid-on neuroinflammation using liquid chromatography-tandem mass spectrometry. LPS changed N-glycosylation in the microglial glycocalyx altering high mannose and sialofucosylated N-glycans, suggesting the dysregulation of mannosidases, fucosyltransferases, and sialyltransferases. The results were consistent as we observed the restoration effect of the fatty acids, especially oleic acid, on the LPS-treated microglia, specifically on the high mannose and sialofucosylated glycoforms of translocon-associated proteins, SSRA and SSRB along with the cell surface proteins, CD63 and CD166. In addition, proteomic analysis and in silico modeling substantiated the potential of fatty acids in reverting the effects of LPS on microglial N-glycosylation. Our results showed that N-glycosylation is likely affected by diet by restoring alterations following LPS challenge, which may then influence the disease state.

Do NPM1 and FLT3-ITD mutations modify prognosis in patients treated with non-intensive regimens?

FLT3-ITD and NPM1 mutations are key to defining the genetic risk profile of acute myeloid leukemia (AML). We aimed to assess the prognostic features of the FLT3-ITD and NPM1 mutations in old and/or unfit individuals with AML treated with non-intensive therapies in the era before azacitidine-venetoclax approbation. The results of various non-intensive regimens were also compared. We conducted a retrospective analysis that included patients treated with different non-intensive regimens, between 2007 and 2020 from PETHEMA AML registry. We compiled 707 patients with a median age of 74 years and median follow-up time of 37.7 months. FLT3-ITD patients (N = 98) showed a non-significant difference in overall survival (OS) compared to FLT3-ITD negative-patients (N = 608) (P = 0.17, median OS was 5 vs 7.3 months respectively). NPM1-mutated patients (N = 144) also showed a non-significant difference with NPM1 wild type (N = 519) patients (P = 0.25, median OS 7.2 vs 6.8 respectively). In the Cox regression analysis neither NPM1 nor FLT3-ITD nor age were significant prognostic variables for OS prediction. Abnormal karyotype and a high leukocyte count showed a statistically significant deleterious effect. Azacitidine also showed better survival compared to FLUGA (low dose cytarabine plus fludarabine). NPM1 and FLT3-ITD seem to lack prognostic value in older/unfit AML patients treated with non-intensive regimens other than azacitidine-venetoclax combination.

Tratamiento de la hiperpigmentación periocular con fuentes de luz / Treatment of periorbital hyperpigmentation using light devices

El tratamiento de la ojera supone una de las demandas más habituales en la consulta de estética para mejorar la imagen de cansancio, tristeza o envejecimiento que perciben nuestros pacientes. Además, se trata de un problema de etiología multifactorial y frente al que disponemos de un amplio abanico de tratamientos.El objetivo de la presente revisión es analizar la mejor evidencia disponible para el tratamiento de la ojera hiperpigmentada con fuentes de luz. Se han revisado 208 artículos que cumplían los criterios de búsqueda, incluyendo finalmente 14 para dar plena consideración en la revisión.Múltiples fuentes de luz han demostrado ser eficaces para el tratamiento de la pigmentación periorbitaria. Los resultados más prometedores se obtienen con luz pulsada intensa y láser rubí en combinación con despigmentantes. Para el tratamiento de la pigmentación junto con redensificación y disminución de arrugas destacan el láser CO2 y el láser erbium:yttrium scandium gallium garnet. Los láseres neodymium-doped yttrium aluminium garnet, alejandrita y diodo fueron los que reportaron resultados más moderados con su uso aislado. El tratamiento adyuvante con despigmentantes mejora resultados y reduce la incidencia de hiperpigmentación postinflamatoria.Es necesaria una mejor estandarización en la medida de los resultados en los cambios de la pigmentación. Además, sería recomendable realizar ensayos clínicos con resultados objetivables y que combinen varias fuentes de luz para el tratamiento no solo de la pigmentación periorbitaria, sino de la ojera de forma integral. (AU)

The treatment of dark circles is one of the most common request from the patients attending to the esthetics clinic. A tired, sad or aged appearance is perceived by our patients. Moreover, it is a multifactorial problem and we could treat it with a wide range of treatments.With this systematic review, we want to check the best available evidence regarding the treatment of periorbital hyperpigmentation using light devices. We have reviewed 208 papers, including 14 of them for full consideration.Several light sources have demonstrated to be effective treating pigmented dark circles. The best results have been reported using intense pulsed light and rubi laser together with depigmenting substances. If we want to treat periocular hyperpigmentation, soft wrinkles, rhytides and skin density we should use carbon dioxide laser or erbium:yttrium scandium gallium garnet. The neodymium-doped yttrium aluminium garnet, alexandrite and diode lasers were the ones giving the worst outcome regarding pigmentation treatment. The concomitant use of depigmenting treatment may help getting better results and reducing the rate of post-inflammatory hyperpigmentation.A better standardization and measuring of the obtained results is needed regarding pigmentation changes. We must keep on investigating on this topic with new clinical trials measuring objective results and combining different light devices for a multifactorial treatment of the dark circles. (AU)

Treatment of periorbital hyperpigmentation using light devices.

The treatment of dark circles is one of the most common request from the patients attending to the esthetics clinic. A tired, sad or aged appearance is perceived by our patients. Moreover, it is a multifactorial problem and we could treat it with a wide range of treatments. With this systematic review, we want to check the best available evidence regarding the treatment of periorbital hyperpigmentation using light devices. We have reviewed 208 papers, including 14 of them for full consideration. Several light sources have demonstrated to be effective treating pigmented dark circles. The best results have been reported using intense pulsed light and rubi laser together with depigmenting substances. If we want to treat periocular hyperpigmentation, soft wrinkles, rhytides and skin density we should use carbo dioxide laser or Erbium:Yttrium Scandium Gallium Garnet. The Neodymium-Doped Yttrium Aluminium Garnet, alexandrite and diode lasers were the ones giving the worst outcome regarding pigmentation treatment. The concomitant use of depigmenting treatment may help getting better results and reducing the rate of post inflammatory hyperpigmentation. A better standardization and measuring of the obtained results is needed regarding pigmentation changes. We must keep on investigating on this topic with new clinical trials measuring objective results and combining different light devices for a multifactorial treatment of the dark circles.

Gestational surrogacy / Philippine Journal of Obstetrics and Gynecology

@#Some women may not be able to carry their own children even when capable of conceiving biological offspring. In-vitro fertilization and embryo-transfer (IVF-ET) through surrogacy can now make this possible for these women. Surrogacy however, is still considered unacceptable in the Philippines due to moral and legal issues. This article will explore the need and acceptability of surrogacy in this age of IVF-ET in a country where the prevailing social norms and religious values still disapprove of third-party assisted reproductive technology (ART). Medical indications that would benefit from gestational surrogacy were enumerated and briefly discussed. The differentiation between traditional and gestation surrogacy, as well as commercial and altruistic surrogacy were defined. IVF with gestational surrogacy is a feasible solution to a number of medical difficulties in the carrying of a gestation. Strictly regulating the practice and restricting its use only to cases with legitimate medical indications will prevent its misuse and exploitation. Moral issues, admittedly will still remain an issue particularly for commercial surrogacy. However, limiting these only to altruistic and gestational surrogacy in some cases may be an acceptable compromise.

Predicted COVID-19 molecular effects on endometrium reveal key dysregulated genes and functions.

COVID-19 exerts systemic effects that can compromise various organs and systems. Although retrospective and in silico studies and prospective preliminary analysis have assessed the possibility of direct infection of the endometrium, there is a lack of in-depth and prospective studies on the impact of systemic disease on key endometrial genes and functions across the menstrual cycle and window of implantation. Gene expression data have been obtained from (i) healthy secretory endometrium collected from 42 women without endometrial pathologies and (ii) nasopharyngeal swabs from 231 women with COVID-19 and 30 negative controls. To predict how COVID-19-related gene expression changes impact key endometrial genes and functions, an in silico model was developed by integrating the endometrial and COVID-19 datasets in an affected mid-secretory endometrium gene co-expression network. An endometrial validation set comprising 16 women (8 confirmed to have COVID-19 and 8 negative test controls) was prospectively collected to validate the expression of key genes. We predicted that five genes important for embryo implantation were affected by COVID-19 (downregulation of COBL, GPX3 and SOCS3, and upregulation of DOCK2 and SLC2A3). We experimentally validated these genes in COVID-19 patients using endometrial biopsies during the secretory phase of the menstrual cycle. The results generally support the in silico model predictions, suggesting that the transcriptomic landscape changes mediated by COVID-19 affect endometrial receptivity genes and key processes necessary for fertility, such as immune system function, protection against oxidative damage and development vital for embryo implantation and early development.

Factors associated with screening failure and study withdrawal in multidrug-resistant TB.

SETTING: Multidrug-resistant TB (MDR-TB) clinical trial in Lima, Peru and Cape Town, South Africa.OBJECTIVE: To identify baseline factors associated with screening failure and study withdrawal in an MDR-TB clinical trial.DESIGN: We screened patients for a randomized, blinded, Phase II trial which assessed culture conversion over the first 6 months of treatment with varying doses of levofloxacin plus an optimized background regimen (ClinicalTrials.gov: NCT01918397). We identified factors for screening failure and study withdrawal using Poisson regression to calculate prevalence ratios and Cox proportional hazard regression to calculate hazard ratios. We adjusted for factors with P < 0.2.RESULTS: Of the 255 patients screened, 144 (56.5%) failed screening. The most common reason for screening failure was an unsuitable resistance profile on sputum-based molecular susceptibility testing (n = 105, 72.9%). No significant baseline predictors of screening failure were identified in the multivariable model. Of the 111 who were enrolled, 33 (30%) failed to complete treatment, mostly for non-adherence and consent withdrawal. No baseline factors predicted study withdrawal in the multivariable model.CONCLUSION: No baseline factors were independently associated with either screening failure or study withdrawal in this secondary analysis of a MDR-TB clinical trial.