Lipidomics signature in post-COVID patient sera and its influence on the prolonged inflammatory response.

BACKGROUND: The ongoing issues with post-COVID conditions (PCC), where symptoms persist long after the initial infection, highlight the need for research into blood lipid changes in these patients. While most studies focus on the acute phase of COVID-19, there's a significant lack of information on the lipidomic changes that occur in the later stages of the disease. Addressing this knowledge gap is critical for understanding the long-term effects of COVID-19 and could be key to developing personalized treatments for those suffering from PCC. METHODS: We employed untargeted lipidomics to analyze plasma samples from 147 PCC patients, assessing nearly 400 polar lipids. Data mining (DM) and machine learning (ML) tools were utilized to decode the results and ascertain significant lipidomic patterns. RESULTS: The study uncovered substantial changes in various lipid subclasses, presenting a detailed profile of the polar lipid fraction in PCC patients. These alterations correlated with ongoing inflammation and immune response. Notably, there were elevated levels of lysophosphatidylglycerols (LPGs) and phosphatidylethanolamines (PEs), and reduced levels of lysophosphatidylcholines (LPCs), suggesting these as potential lipid biomarkers for PCC. The lipidomic signatures indicated specific anionic lipid changes, implicating antimicrobial peptides (AMPs) in inflammation. Associations between particular medications and symptoms were also suggested. Classification models, such as multinomial regression (MR) and random forest (RF), successfully differentiated between symptomatic and asymptomatic PCC groups using lipidomic profiles. CONCLUSIONS: The study's groundbreaking discovery of specific lipidomic disruptions in PCC patients marks a significant stride in the quest to comprehend and combat this condition. The identified lipid biomarkers not only pave the way for novel diagnostic tools but also hold the promise to tailor individualized therapeutic strategies, potentially revolutionizing the clinical approach to managing PCC and improving patient care.

Detection of coca alkaloids in oral fluid from coca leaf (tea) consumers: using solid phase extraction to improve validation parameters and widen the detection window.

Hygrine and cuscohygrine, two coca leaf alkaloids, have been previously proposed as markers to differentiate legal and illegal cocaine consumption. This is a very common problem in some countries of South America, where the consumption of coca leaves has a long tradition. Analytical methods focusing on the assessment of coca leaf alkaloids, such as cuscohygrine, hygrine, tropacocaine and t-cinnamoylcocaine, in oral fluid are virtually non-existent in forensic toxicology laboratories worldwide due to their lack of application. However, the problem of differentiating legal and illegal cocaine use in criminal justice, DUID (drug-impaired driving) and WDT (workplace drug testing) programs is growing. Therefore, researchers are obliged to develop methods to measure coca leaf alkaloids (cuscohygrine, hygrine and t-cinnamoylcocaine) in biological matrices for further validation for routine analyses in forensic toxicology laboratories. This work aims to optimize a previously published separation method by protein precipitation in oral fluid by using solid-phase extraction (SPE) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) operating in multiple reaction monitoring (MRM) mode. The use of SPE allowed the matrix effect and the background to be reduced in the chromatograms due to the obtained cleaner extracts. Consequently, improved detection and quantification limits were reached. Findings showed that the detection windows for coca leaf alkaloids were longer than three hours in real oral fluid samples from volunteers who drank a cup of coca tea. These detection windows are quite higher than those previously obtained when using the method based on separation by protein precipitation.

Dynamically Induced Symmetry Breaking and Out-of-Equilibrium Topology in a 1D Quantum System.

Nontrivial topology in lattices is characterized by invariants-such as the Zak phase for one-dimensional (1D) lattices-derived from wave functions covering the Brillouin zone. We realize the 1D bipartite Rice-Mele (RM) lattice using ultracold ^{87}Rb and focus on lattice configurations possessing various combinations of chiral, time-reversal, and particle-hole symmetries. We quench between configurations and use a form of quantum state tomography, enabled by diabatically tuning lattice parameters, to directly follow the time evolution of the Zak phase as well as a chiral winding number. The Zak phase evolves continuously; however, when chiral symmetry transiently appears in the out-of-equilibrium system, the chiral winding number becomes well defined and can take on any integer value. When quenching between two configurations obeying the same three symmetries, the Zak phase is time independent; we confirm the dynamically induced symmetry breaking predicted in [McGinley and Cooper, Phys. Rev. Lett. 121, 090401 (2018)PRLTAO0031-900710.1103/PhysRevLett.121.090401] that chiral symmetry is periodically restored, at which times the winding number changes by ±2, yielding values that are not present in the native RM Hamiltonian.

Floquet Engineering Topological Dirac Bands.

We experimentally realized a time-periodically modulated 1D lattice for ultracold atoms featuring a pair of linear bands, each with a Floquet winding number. These bands are spin-momentum locked and almost perfectly linear everywhere in the Brillouin zone: a near-ideal realization of the 1D Dirac Hamiltonian. We characterized the Floquet winding number using a form of quantum state tomography, covering the Brillouin zone and following the micromotion through one Floquet period. Last, we altered the modulation timing to lift the topological protection, opening a gap at the Dirac point that grew in proportion to the deviation from the topological configuration.

Farmacovigilancia de las vacunas frente a la COVID-19 en farmacias comunitarias VI. Elección de la segunda dosis / Pharmacovigilance of COVID-19 vaccines in community pharmacies VI. Choice of second dose

INTRODUCCIÓN: en Galicia se administró Vaxzevria® (VZ) como primera dosis de la vacuna frente a Covid-19 a sanitarios y trabajadores esenciales menores de 60 años. Tras la alarma social por problemas de trombosis con trombopenia detectados, la administración sanitaria gallega permitió elegir la vacuna que recibirían como segunda dosis, repitiendo con Vaxzevria® o cambiar a Comirnaty® (CO).OBJETIVOS: conocer el número de vacunados que eligen una 2ª dosis diferente, las razones por la que eligieron una u otra y las fuentes de información utilizadas para tomar la decisión.MÉTODOS: Diseño: estudio observacional transversal, en una farmacia tras la administración de la 2ª dosis de vacuna Covid-19 en mayo/junio de 2021.Sujetos: trabajadores esenciales, vacunados con Vaxzevria®, mayores de edad, que firmaron consentimiento informado. Variables: demográficas, número de vacunados que eligen una vacuna diferente como 2ª dosis, razones para ello, fuentes de información. Procedimiento: las preguntas correspondientes a este estudio estaban incluidas en el cuaderno de recogida de datos utilizado en el proyecto FARMACOVIGILANCIA DE LAS VACUNAS COVID-19. Consideraciones éticas: el estudio del que forma parte recibió informe favorable del Comité Ético de Investigación con Medicamentos de Galicia. Resultados Se entrevistó a 28 personas, 17 (60,7 %) mujeres, 11 (39,3 %) hombres; 19 (67,9 %) sanitarios. 3 (10,7 %) eligieron como 2ª dosis Comirnaty®, 2 mujeres y 1 hombre y 1 hombre no recibió la 2ª dosis por contagio tras la 1ª.Razones para repetir vacuna: recomendación de autoridades sanitarias/instituciones científicas, 13 (54,2 %); “por no cambiar”, 14 (58,3 %); evidencia científica, 8 (33,3 %). 10 (41,7 %) manifestaron más de un motivo. (AU)

Farmacovigilancia de las vacunas frente a la COVID-19 en farmacias comunitarias IV. Segunda dosis / Pharmacovigilance of COVID-19 vaccines in community pharmacies IV. Second dose

OBJETIVO: conocer tipo y frecuencia de sospechas de reacciones adversas (RA) experimentadas por la población general con la segunda dosis de la vacuna frente a COVID-19 y la repercusión sobre su actividad diaria.MÉTODOS: se describen detalladamente en el protocolo del Proyecto. Procedimiento: Seguimiento de los participantes incorporados al estudio tras la 2ª dosis, registrándose las nuevas sospechas de RA experimentadas. Resultados10 farmacias de la provincia de Pontevedra y 2 de Ourense incorporaron vacunados. Tras la 2ª dosis se redujeron en 88 (11,3 %): 43 habían recibido COVID-19 Vaccine Janssen® (JA), 39 se habían contagiado entre dosis, 1 no quiso vacunarse por RA de la 1ª dosis y con 5 no se pudo contactar. Quedaron 693 participantes, 441 (63,6 %) mujeres y 252 (36,4 %) hombres. Media de edad 57,8 (DE=18,0) (rango=18-97). 416 (60,0 %) recibieron Comirnaty® Pfizer- BioNtech (CO), 177 (25,5 %) Vaxzevria® (VZ) y 100 (14,5 %) Spikevax® Moderna (SP). 175 (25,2 %) utilizaron medicamentos como profilaxis de posibles RA. 145 (82,9 %) paracetamol.312 (45,0 %) vacunados, 218 mujeres (49,4 %) y 94 (37,1 %) hombres (p<0,01) refirieron al menos una reacción adversa: 183 (43,9 %) CO, 66 (37,3 %) VZ y 63 (63,0 %) SP. El número de reacciones adversas manifestadas por los encuestados fue de 971, con un máximo de 11 por vacunado, resultando las más prevalentes, que afectaron a >10 % de estos: dolor en punto de inyección 197 (28,4 %), cansancio/fatiga 141 (20,3 %), dolor muscular 111 (16,0 %), cefalea 95 (13,7 %) y fiebre 84 (12,1 %). (AU)

Identification of extraocular extension in uveal melanoma by ophthalmological ultrasound.

BACKGROUND AND PURPOSE: Uveal melanoma is the most common primary malignant intraocular tumour in the adult population, with a survival rate of 50% despite advances in treatment and knowledge of this disease. The presence of extraocular extension (EE) worsens the prognosis of these patients, so its proper identification can ensure its management and early intervention. Ophthalmological ultrasound is the technique of choice for the diagnosis and follow-up of these patients, both of the anterior EE using ultrasonic biomicroscopy (UBM), and the posterior EE using A and B ultrasound. The aim of this study is to describe the ultrasound characteristics of the BMU and the A and B ultrasound. MATERIAL AND METHODS: A descriptive and retrospective study is carried out on patients diagnosed with uveal melanoma (UM) and EE from 2003 to 2019. The ultrasound characteristics of the local disease and the follow-up after treatment were recorded completely and at each visit. In the case of anterior EE, photographs of the anterior segment and UBM were taken, while those involving the posterior segment were explored under A and B mode ultrasound. All enucleated eyes were sent for anatomopathological study. RESULTS: Ten patients with an average age of 72.3 years were included. The largest proportion of them were medium-sized tumours, followed by large and small ones. The most frequent morphology of the primary tumour was cupuliform. All the EE presented lower internal reflectivity compared to the primary tumour. No trans-scleral connection bridges were found between the primary tumour and the EE in the ultrasound studies. 50% of patients underwent primary enucleation at the time of diagnosis of intraocular MU due to the presence of the EE, and the remaining 50% presented the EE after initial treatment of the primary tumour with I125 brachytherapy. Sixty percent of the patients presented with posterior EE, and were therefore diagnosed with ultrasound A and B. The most frequent histopathological pattern with 87.5% of patients was the epithelioid pattern. DISCUSSION: Ultrasound scanning in patients with MU is mandatory for diagnosis and follow-up of EE. BMU and A and B ultrasound are the test of choice for anterior and posterior EE, respectively. EE have particular ultrasound characteristics such as low internal reflectivity, regularity of their contour and their location usually adjacent to the base of the primary intraocular tumor.

Identificación de extensión extraocular en el melanoma uveal mediante ecografía oftalmológica / Identification of Extraocular Extension in Uveal Melanoma by Ophthalmological Ultrasound

Antecedentes y objetivoEl melanoma uveal es el tumor primario maligno intraocular más frecuente en la población adulta, con una tasa de supervivencia del 50% a pesar de los avances en el tratamiento y conocimiento de esta enfermedad. La presencia de extensión extraocular (EE) empeora el pronóstico de estos pacientes, por lo que su correcta identificación puede asegurar su manejo e intervención temprana. La ecografía oftalmológica es la técnica de elección para el diagnóstico y seguimiento de estos pacientes, tanto de la EE anterior mediante biomicroscopía ultrasónica (UBM), como de la EE posterior mediante ecografía A y B. El objetivo de este estudio es describir las características ecográficas de la UBM y de la ecografía A y B.Material y métodosSe realiza un estudio descriptivo y retrospectivo de los pacientes diagnosticados de melanoma uveal (UM) y EE desde 2003 hasta 2019. Las características ecográficas de la enfermedad local y el seguimiento luego del tratamiento se registraron de maneracompleta y en cada visita. En caso de EE anteriores se realizaron fotografías de segmento anterior y BMU, por el contrario las que involucran el segmento posterior se exploraron bajo ecografía modo A y B. Todos los ojos enucleados se enviaron para su estudio anatomopatológico.

Background and purposeUveal melanoma is the most common primary malignant intraocular tumour in the adult population, with a survival rate of 50% despite advances in treatment and knowledge of this disease. The presence of extraocular extension (EE) worsens the prognosis of these patients, so its proper identification can ensure its management and early intervention. Ophthalmological ultrasound is the technique of choice for the diagnosis and follow-up of these patients, both of the anterior EE using ultrasonic biomicroscopy (UBM), and the posterior EE using A and B ultrasound. The aim of this study is to describe the ultrasound characteristics of the BMU and the A and B ultrasound.Material and methodsA descriptive and retrospective study is carried out on patients diagnosed with uveal melanoma (UM) and EE from 2003 to 2019. The ultrasound characteristics of the local disease and the follow-up after treatment were recorded completely and at each visit. In the case of anterior EE, photographs of the anterior segment and UBM were taken, while those involving the posterior segment were explored under A and B mode ultrasound. All enucleated eyes were sent for anatomopathological study.

The impact of fluorescence angiography on anastomotic leak rate following transanal total mesorectal excision for rectal cancer: a comparative study.

BACKGROUND: Anastomotic leak (AL) is the most feared complication in colorectal surgery. Indocyanine green (ICG) fluorescence angiography allows for real-time intraoperative evaluation of bowel perfusion. This study aimed to assess the impact of ICG on perioperative outcomes in patients treated with transanal total mesorectal excision (TaTME) for rectal cancer. METHODS: Comparative study based on a retrospective analysis of prospectively collected data, to validate the use of ICG assessment (ICGA) during TaTME (November/2011-June/2018). The primary outcome was the clinical AL rate. The secondary outcomes included modification of proximal colonic transection, anastomotic redo, additional surgical maneuvers and surgical morbidity. RESULTS: Two hundred and eighty-four patients were included, 204 (71.8%) in non-ICG group and 80 (28.2%) in ICG group. No significant differences were found in patient and tumor features. Mean anastomotic height was 4.85 cm vs. 5.04 cm (p = 0.500), diverting stoma was constructed in 205 patients (72.1% vs. 72.5%; p = 0.941). Fluorescence angiography modified the surgical plan in 23 patients (28.7%). AL was diagnosed in 23 patients (11.3%) in the non-ICG group and in two patients (2.5%) in the ICG group (p = 0.020). Postoperative intraabdominal collection was diagnosed in 19 patients (7.4% vs. 5.1%; p = 0.490), and reintervention was needed in 24 patients (10.8% vs. 7.6%; p = 0.420). Median length of hospital stay was 6.0 (IQR 5.0-9) vs. 4.0 (IQR 3.0-8.5) (p = 0.005). ICGA was found as independent protective factor for AL in the multivariate analysis of the whole cohort (n = 284) (OR 0.142; 95% CI 0.032-0.633; p = 0.010). CONCLUSION: ICG fluorescence angiography modified the proximal colonic transection in more than one-quarter of patients, leading to a significant decrease of AL rate.

Three-year outcome after transanal versus laparoscopic total mesorectal excision in locally advanced rectal cancer: a multicenter comparative analysis.

BACKGROUND: For patients with mid and distal rectal cancer, robust evidence on long-term outcome and causal treatment effects of transanal total mesorectal excision (TaTME) is lacking. This multicentre retrospective cohort study aimed to assess whether TaTME reduces locoregional recurrence rate compared to laparoscopic total mesorectal excision (LapTME). METHODS: Consecutive patients with rectal cancer within 12 cm from the anal verge and clinical stage II-III were selected from three institutional databases. Outcome after TaTME (Nov 2011 - Feb 2018) was compared to a historical cohort of patients treated with LapTME (Jan 2000 - Feb 2018) using the inverse probability of treatment weights method. The primary endpoint was three-year locoregional recurrence. RESULTS: A total of 710 patients were analysed, 344 in the TaTME group and 366 in the LapTME group. At 3 years, cumulative locoregional recurrence rates were 3.6% (95% CI, 1.1-6.1) in the TaTME group and 9.6% (95% CI, 6.5-12.7) in the LapTME group (HR = 0.4; 95% CI, 0.23-0.69; p = 0.001). Three-year cumulative disease-free survival rates were 74.3% (95% CI, 68.8-79.8) and 68.6% (95% CI, 63.7-73.5) (HR = 0.82; 95% CI, 0.65-1.02; p = 0.078) and three-year overall survival 87.2% (95% CI, 82.7-91.7) and 82.2% (95% CI, 78.0-86.2) (HR = 0.74; 95% CI, 0.53-1.03; p = 0.077), respectively. In patients who underwent sphincter preservation procedures, TaTME was associated with a significantly better disease-free survival (HR = 0.78; 95% CI, 0.62-0.98; p = 0.033). CONCLUSIONS: These findings suggest that TaTME may improve locoregional recurrence and disease-free survival rates among patients with mid and distal locally advanced rectal cancer.

Creating solitons with controllable and near-zero velocity in Bose-Einstein condensates.

Established techniques for deterministically creating dark solitons in repulsively interacting atomic Bose-Einstein condensates (BECs) can only access a narrow range of soliton velocities. Because velocity affects the stability of individual solitons and the properties of soliton-soliton interactions, this technical limitation has hindered experimental progress. Here we create dark solitons in highly anisotropic cigar-shaped BECs with arbitrary position and velocity by simultaneously engineering the amplitude and phase of the condensate wave function, improving upon previous techniques which explicitly manipulated only the condensate phase. The single dark soliton solution present in true one-dimensional (1D) systems corresponds to the kink soliton in anisotropic three-dimensional systems and is joined by a host of additional dark solitons, including vortex ring and solitonic vortex solutions. We readily create dark solitons with speeds from zero to half the sound speed. The observed soliton oscillation frequency suggests that we imprinted solitonic vortices, which for our cigar-shaped system are the only stable solitons expected for these velocities. Our numerical simulations of 1D BECs show this technique to be equally effective for creating kink solitons when they are stable. We demonstrate the utility of this technique by deterministically colliding dark solitons with domain walls in two-component spinor BECs.

Performance of Indocyanine green for sentinel lymph node mapping and lymph node metastasis in colorectal cancer: a diagnostic test accuracy meta-analysis.

BACKGROUND: Indocyanine green has been widely employed as a secure and easy technique for sentinel lymph node mapping in different types of cancer. Nonetheless, the usage of Indocyanine green has not been fully implemented due to the heterogeneous results found in published studies. Thus, the objective of this meta-analysis is to evaluate the overall performance of Indocyanine green for sentinel lymph node mapping and node metastasis in patients undergoing colorectal cancer surgery. METHODS: An extensive systematic search was performed to identify relevant studies in English and Spanish with no time limit restrictions. For the meta-analysis, a hierarchical summary receiver operating characteristic curve (HSROCs) was constructed, and quantitative data synthesis was performed using random effects models. Specificity, sensitivity, positive, and negative likelihood ratios were obtained from the corresponding HSROC. Between-study heterogeneity was visually evaluated using Galbraith plot, and publication bias was quantified using Deeks' method. RESULTS: A total of 11 studies were included for analysis. The pooled detection rate for sentinel lymph node mapping was 91% (80-98%). Covariates significantly influencing the pooled detection rate were having colon cancer (estimate: 1.3001; 1.114 to 1.486; p < 0.001) and the usage of a laparoscopic approach (estimate: 1.3495; 1.1029 to 1.5961; p < 0.001). The performance of Indocyanine green for the detection of metastatic lymph nodes yielded an area under the roc curve of 66.5%, sensitivity of 64.3% (51-76%), and specificity of 65% (36-85%). CONCLUSIONS: Indocyanine green for the detection of sentinel lymph node mapping demonstrates better accuracy when used in colonic cancer and by a laparoscopic approach. Nevertheless, its overall performance for the detection of lymph node metastasis is poor.

5G-assisted telementored surgery.

Safe and effective implementation of remote surgery and telementoring can have significant limitations. Fifth-generation (5G) wireless networks could be useful in overcoming these drawbacks. As a proof of concept, the authors present technical and clinical details of two procedures assisted by telementoring using 5G that were also broadcast live. Secure remote access advice.

Perfil de alcaloides de la hoja de coca en el fluido oral de un mascador de hoja de coca y un bebedor de té de coca: Estudio preliminar / Coca alkaloids profile in oral fluid from people chewing coca leaves and drinking coca tea: Preliminary study

Actualmente el fluido oral (FO) es aceptado como una matriz biológica alternativa para detectar drogas en toxicología clínica y forense. En países como Argentina donde el uso de hojas de coca (mascar hojas de coca o beber té de coca) es legal son necesarios procedimientos adecuados para logar una clara diferenciación entre los individuos que usan las hojas de coca de manera legal de aquéllos que usan cocaína en forma ilegal. Poca es la información que hay en la literatura sobre el perfil de los alcaloides de la hoja de coca en FO de personas que mascan hojas de coca o toman té de coca y hasta el presente trabajo no se hallaron datos sobre el perfil en FO de la higrina (HIG) y cuscohigrina (CUS). De este estudio preliminar participaron dos voluntarios. Los resultados mostraron que la CUS e HIG siguieron siendo positivas después que la cocaína (COC) y benzoilecgonina (BE) cayeron por debajo de los valores cut- off propuestos por las guías internacionales para FO en casos de screening (15 a 20 ng/ mL) y de confirmación (8 a 10 ng/mL) en el caso del mascador de coca. En el participante que tomó una taza de té de coca, en el último punto examinado (1 h) resultó ser positivo para la COC y BE y también para la CUS e HIG. El FO podría ser una muestra útil para confirmar el uso legal de la hoja de coca, aun cuando futuros estudios son necesarios para corroborar estos primeros datos.

Nowadays oral fluid (OF) is accepted as an alternative biological sample for detecting drugs in clinical and forensic toxicology. In countries like Argentina, where the use of coca leaves (coca leaves chewing and coca tea drinking) is legal, adequate procedures are required to allow a clear differentiation between people who use coca leaves (legal practice) and those who use cocaine (illicit practice). There is scarce literature regarding coca leaf alkaloids profile in OF from people who chew coca leaves and drink coca tea. Until now, coca leaf alkaloids profile of hygrine (HYG) and cuscohygrine (CUS) in OF were not described in the literature. The current preliminary study was performed with two healthy volunteers. In this research CUS and HYG have been found to be positive (detectable) even when cocaine (COC) and benzoylecgonine (BE) are dropped below the cut-off values proposed by international guidelines for screening (15 to 20 ng/mL), and confirmation (8 to 10 ng/mL) in OF. In addition, CUS and HYG were also found to be positive at the same time of the last detection of COC and BE after coca tea consumption. The OF would be a useful sample to confirm the legal use of coca leaf, even when more researches are therefore needed.

Sauter-Schwinger effect with a quantum gas.

The creation of particle-antiparticle pairs from vacuum by a large electric field is at the core of quantum electrodynamics. Despite the wide acceptance that this phenomenon occurs naturally when electric field strengths exceed E c ≈ 1018 Vm-1, it has yet to be experimentally observed due to the limitations imposed by producing electric fields at this scale. The high degree of experimental control present in ultracold atomic systems allow experimentalists to create laboratory analogs to high-field phenomena. Here we emulated massive relativistic particles subject to large electric field strengths, thereby quantum-simulated particle-antiparticle pair creation, and experimentally explored particle creation from 'the Dirac vacuum'. Data collected from our analog system spans the full parameter regime from low applied field (negligible pair creation) below the Sauter-Schwinger limit, to high field (maximum rate of pair creation) far in excess of the Sauter-Schwinger limit. In our experiment, we perform direct measurements on an analog atomic system and show that this high-field phenomenon is well-characterized by Landau-Zener tunneling, well known in the atomic physics context, and we find full quantitative agreement with theory with no adjustable parameters.