A particulate blood analogue based on artificial viscoelastic blood plasma and RBC-like microparticles at a concentration matching the human haematocrit.

There has been enormous interest in the production of fluids with rheological properties similar to those of real blood over the last few years. Application fields range from biomicrofluidics (microscale) to forensic science (macroscale). The inclusion of flexible microparticles in blood analogue fluids has been demonstrated to be essential in order to reproduce the behaviour of blood flow in these fields. Here, we describe a protocol to produce a whole human blood analogue composed of a proposed plasma analogue and flexible spherical microparticles that mimic the key structural attributes of RBCs (size and mechanical properties), at a concentration matching the human haematocrit (∼42% by volume). Polydimethylsiloxane (PDMS) flexible microparticles were used to mimic RBCs, whose capability to deform is tunable by means of the mixing ratio of the PDMS precursor. Their flow through glass micronozzles allowed us to find the appropriate mixing ratio of PDMS to have approximately the same Young's modulus (E) as that exhibited by real RBCs. Shear and extensional rheology and microrheology techniques were used to match the properties exhibited by human plasma and whole blood at body temperature (37 °C). Finally, we study the flow of our proposed fluid through a microfluidic channel, showing the in vitro reproduction of the multiphase flow effects taking place in the human microcirculatory system, such as the cell-free layer (CFL) and the Fåhræus-Lindqvist effect. A macroscale application in the field of forensic science is also presented, concerning the impact of our blood analogue droplets on a solid surface for bloodstain pattern analysis.

A critical test of twelve methods for estimating age using radiographic staging of developing teeth on a sample of 6- to 15-year-old children from Mérida, Yucatán (México).

Cross-population applicability of osteological and dental methods is a known issue in forensic anthropology, but very little is known about whether differences between populations are due to ancestry, environment effects, or even the statistical approach utilized for developing the methods. This study wishes to add to the discussion of population-specificity of dental age estimation methods and examine the impact of their statistical basis on their accuracy and precision. These parameters were estimated by testing 12 different dental age estimation techniques on a sample of 182 panoramic radiographs of children between the ages of 6 and 15 years (110 girls and 72 boys) from the city of Mérida in Yucatán, México. None of the 12 methods selected is based on Mexican samples. Dental maturation was scored following and methods tested employed two dental scoring schemes: Moorrees, Fanning, and Hunt's (MFH) 13-/14-stage system and Demirjian's 8-stage system. Results show that methods derived from more geographically specific groups do not fare better or worse than methods developed on more diverse and inclusive international samples, even if no methods specific to Mexicans were tested. While some of the methods performed very well, and they were not based on a Mexican sample, this suggests that population-specific dental age estimation methods may be relatively unimportant or that population differences in dental maturation are very small. Other issues seemed to have a greater impact on accuracy and precision, such as age dependency, inclusion of the third molar in age assessments, age truncation and age heaping in reference samples, the dental scoring scheme used, and how predicted age is calculated mathematically. As such, findings in this study suggest that validation tests of age estimation methods may not be a useful or reliable means to assess population differences and that these differences need to be more systematically assessed if an argument is to be made for the increased accuracy and precision of population-specific methods. The statistical basis of dental prediction methods seems to have a more significant role in their accuracy and precision outside of their reference sample.

Validation of the bag-mediated filtration system for environmental surveillance of poliovirus in Nairobi, Kenya.

AIMS: This study compared the bag-mediated filtration system (BMFS) and standard WHO two-phase separation methods for poliovirus (PV) environmental surveillance, examined factors impacting PV detection and monitored Sabin-like (SL) PV type 2 presence with withdrawal of oral polio vaccine type 2 (OPV2) in April 2016. METHODS AND RESULTS: Environmental samples were collected in Nairobi, Kenya (Sept 2015-Feb 2017), concentrated via BMFS and two-phase separation methods, then assayed using the WHO PV isolation algorithm and intratypic differentiation diagnostic screening kit. SL1, SL2 and SL3 were detected at higher rates in BMFS than two-phase samples (P < 0·05). In BMFS samples, SL PV detection did not significantly differ with volume filtered, filtration time or filter shipment time (P > 0·05), while SL3 was detected less frequently with higher shipment temperatures (P = 0·027). SL2 was detected more frequently before OPV2 withdrawal in BMFS and two-phase samples (P < 1 × 10-5 ). CONCLUSIONS: Poliovirus was detected at higher rates with the BMFS, a method that includes a secondary concentration step, than using the standard WHO two-phase method. SL2 disappearance from the environment was commensurate with OPV2 withdrawal. SIGNIFICANCE AND IMPACT OF THE STUDY: The BMFS offers comparable or improved PV detection under the conditions in this study, relative to the two-phase method.

Comparison of oncological outcomes after open and laparoscopic re-resection of incidental gallbladder cancer.

BACKGROUND: The safety and oncological efficacy of laparoscopic re-resection of incidental gallbladder cancer have not been studied. This study aimed to compare laparoscopic with open re-resection of incidentally discovered gallbladder cancer while minimizing selection bias. METHODS: This was a multicentre retrospective observational cohort study of patients with incidental gallbladder cancer who underwent re-resection with curative intent at four centres between 2000 and 2017. Overall survival (OS) and recurrence-free survival (RFS) were analysed by intention to treat. Inverse probability of surgery treatment weighting using propensity scoring was undertaken. RESULTS: A total of 255 patients underwent re-resection (190 open, 65 laparoscopic). Nineteen laparoscopic procedures were converted to open operation. Surgery before 2011 was the only factor associated with conversion. Duration of hospital stay was shorter after laparoscopic re-resection (median 4 versus 6 days; P < 0·001). Three-year OS rates for laparoscopic and open re-resection were 87 and 62 per cent respectively (P = 0·502). Independent predictors of worse OS were residual cancer found at re-resection (hazard ratio (HR) 1·91, 95 per cent c.i. 1·17 to 3·11), blood loss of at least 500 ml (HR 1·83, 1·23 to 2·74) and at least four positive nodes (HR 3·11, 1·46 to 6·65). In competing-risks analysis, the RFS incidence was higher for laparoscopic re-resection (P = 0·038), but OS did not differ between groups. Independent predictors of worse RFS were one to three positive nodes (HR 2·16, 1·29 to 3·60), at least four positive nodes (HR 4·39, 1·96 to 9·82) and residual cancer (HR 2·42, 1·46 to 4·00). CONCLUSION: Laparoscopic re-resection for selected patients with incidental gallbladder cancer is oncologically non-inferior to an open approach. Dissemination of advanced laparoscopic skills and timely referral of patients with incidental gallbladder cancer to specialized centres may allow more patients to benefit from this operation.

ANTECEDENTES: No se conoce la seguridad y la eficacia oncológica de la re-resección laparoscópica del cáncer incidental de vesícula biliar. Este estudio tiene como objetivo comparar las re-resecciones del cáncer incidental de vesícula biliar por vía laparoscópica y vía abierta, minimizando el sesgo de selección. MÉTODOS: Estudio de cohortes observacional, retrospectivo y multicéntrico de pacientes con cáncer incidental de vesícula biliar que se sometieron a una re-resección con intención curativa en 4 centros entre 2000 y 2017. Se analizó la supervivencia global (overall survival, OS) y la supervivencia libre de recidiva (recurrence free survival, RFS) según intención de tratamiento. Se calculó la probabilidad inversa de la ponderación del tratamiento quirúrgico utilizando puntuación de propensión. RESULTADOS: Se incluyeron 255 pacientes con re-resección (190 por vía abierta y 65 por vía laparoscópica). Se convirtieron 19 pacientes del grupo laparoscópico. El único factor relacionado con la conversión fue la realización de la cirugía antes de año 2011. La mediana de la estancia hospitalaria fue más corta tras la re-resección laparoscópica (4 versus 6 días; P < 0,001). La OS a tres años fue del 87% y del 62% (P = 0,502) para las re-resecciones laparoscópicas y abiertas, respectivamente). Los factores predictivos independientes relacionados con una peor OS fueron el hallazgo de cáncer residual en el momento de la re-resección (cociente de riesgos instantáneos, hazard ratio, HR 1,91; i.c. del 95% 1,17-3,11), una pérdida hemática > 500 ml (HR 1,83; i.c. del 95% 1,23-2,74) y la presencia de ≥ 4 ganglios positivos (HR 3,11; i.c. del 95% 1,46-6,65). En el análisis de riesgo competitivo, la RFS fue mayor para la resección laparoscópica (P = 0,038), pero no hubo diferencias en la OS entre ambos grupos. Los factores predictivos independientes de peor RFS fueron la detección de 1-3 ganglios positivos (HR 2,16; i.c. del 95% 1,29-3,60), ≥ 4 ganglio positivos (HR 4,39; i.c. del 95% 1,96-9,82) y el cáncer residual (HR 2,42; i.c. de 95% 1,46-4,0). CONCLUSIÓN: En pacientes seleccionados, los resultados oncológicos de la re-resección laparoscópica de un cáncer incidental de vesícula biliar no son inferiores a los que se obtienen por vía abierta. Una mayor difusión de las técnicas laparoscópicas avanzadas y una oportuna derivación de los pacientes con cáncer de vesícula biliar incidental a centros especializados podrían permitir que un mayor número de pacientes se beneficiaran de este abordaje.

Erratum: Influence of the Surface Viscosity on the Breakup of a Surfactant-Laden Drop [Phys. Rev. Lett. 118, 024501 (2017)].

This corrects the article DOI: 10.1103/PhysRevLett.118.024501.

Influence of the Surface Viscosity on the Breakup of a Surfactant-Laden Drop.

We examine both theoretically and experimentally the breakup of a pendant drop loaded with an insoluble surfactant. The experiments show that a significant amount of surfactant is trapped in the resulting satellite droplet. This result contradicts previous theoretical predictions, where the effects of surface tension variation were limited to solutocapillarity and Marangoni stresses. We solve numerically the hydrodynamic equations, including not only those effects but also those of surface shear and dilatational viscosities. We show that surface viscosities play a critical role to explain the accumulation of surfactant in the satellite droplet.

Rocuronium pharmacokinetics and pharmacodynamics in the adductor pollicis and masseter muscles.

BACKGROUND: The aim of this study was to characterize the dose-effect relationship of rocuronium at the adductor pollicis and masseter muscles. METHODS: Ten, ASA I, adult patients, received a bolus dose of rocuronium 0.3 mg/kg during propofol based anesthesia. Train-of-four (TOF) was simultaneously monitored at the masseter and the adductor pollicis muscles until recovery. Rocuronium arterial serum concentrations were measured during 120 min. The first twitch of the TOF response was used to characterize the time-effect profile of both muscles using pharmacokinetic-pharmacodynamic analysis in NONMEM. A decrease in NONMEM objective function (∆OFV) of 3.84 points for an added parameter was considered significant at the 0.05 level. RESULTS: Onset time at the masseter (mean ± SD, 1.5 ± 0.9 min) was faster than at the adductor pollicis (2.7 ± 1.4 min, P < 0.05). Recovery, measured as the time to TOF ratio = 0.9 was similar between muscles 29.9 ± 6.7 (adductor pollicis) vs. 29.3 ± 8.1 (masseter). (P = 0.77). The estimated pharmacodynamic parameters [mean (95% CI)] of the adductor pollicis muscle and the masseter muscle were; plasma effect-site equilibration half-time (teq) 3.25 (2.34, 3.69) min vs. 2.86 (1.83, 3.29) min, (∆OFV 383.665); Ce50 of 1.24 (1.13, 1.56) mg/l vs. 1.19 (1.00, 1.21) mg/l, (∆OFV 184.284); Hill coefficient of 3.97 (3.82, 5.62) vs. 4.68 (3.83, 5.71), (∆OFV 78.906). CONCLUSIONS: We found that the masseter muscle has faster onset of blockade and similar recovery profile than adductor pollicis muscle. These findings were best, explained by a faster plasma effect-site equilibration of the masseter muscle to rocuronium.

Simultaneous assessment of protein heterogeneity and affinity by capillary electrophoresis-mass spectrometry.

Most conventional analytical tools for the assessment of protein-protein interactions yield information on the bulk sample. By employing the efficient separation of intact proteins, affinity capillary electrophoresis (ACE) can measure the interaction of components of heterogeneous proteins with a target protein. In this work, the hyphenation of ACE with mass spectrometry (MS) is presented as a novel, highly selective tool for the assessment of protein-protein interactions. The binding of the protease inhibitor aprotinin to trypsinogen was used as protein-protein affinity model. A trypsinogen sample comprising several modifications was analyzed using a background electrolyte of 25 mM ammonium acetate (pH 8.0) containing increasing concentrations of aprotinin (0-300 µM). A capillary coating of polybrene-dextran sulfate-polybrene (PB-DS-PB) was employed to prevent adsorption of the proteins to the capillary wall. The trypsinogen variants were separated and could be assigned based on detected molecular masses and relative migration. In presence of aprotinin, both free and aprotinin-bound trypsinogen were detected revealing a 1:1 binding stoichiometry. For most trypsinogen variants, shifts in electrophoretic mobility were observed upon raising the aprotinin concentration, allowing determination of their dissociation constants (Kd's). The interacting trypsinogen variants showed similar affinity toward aprotinin (Kd's of 3-9 µM), which were not significantly different from the values obtained with ACE-UV and were in agreement with an earlier reported value. The use of the ratio of obtained MS signal intensities of free and protein-protein complex for the determination of Kd's was also explored. Derived Kd values (20-104 µM) for the binding variants were similar to those obtained with direct-infusion MS, but higher and less precise as compared with values based on mobility shifts. The suitability of the ACE-MS methodology for the affinity profiling of heterogeneous protein samples was evaluated, and components with high, medium, or low affinity toward aprotinin could be successfully discriminated.

[A descriptive overview of cases of congenital cytomegalovirus at a tertiary hospital between 2017 and 2023]. / Descriptivo de los casos de citomegalovirus congénitos en un hospital terciario entre 2017-2023.

OBJECTIVE: Cytomegalovirus infection (CMV) is the most common congenital infection in developed countries. The aim of our study was to describe the features of the children that have congenital CMV infection at our hospital for the last 6 years. METHODS: A retrospective descriptive study was designed that included all the children with CMV congenital infection that were diagnosed at tertiary hospital of Madrid Community between 2017 and 2023. RESULTS: Twenty-two children were included. 54.5% have a prenatal diagnosis, 50% of them were in the third trimester, 25% at first trimester and 25% at the second. 22.7% were preterm. CMV was isolated in all the samples with CV more than 1000 copies/ml. When CMV was made in blood, 11/22 (50%) had a high CV. Only one newborn had a high CV at CRL. 44% have affectation at transfontanellar ultrasound evidenced by vasculopathy (62%), intraventricular hemorrhage (IVH) or periventricular calcifications (20%). 68% were asymptomatic, al though 20% had a retarded intrauterine growth (RIG) at birth or clinical features or analytical were objectified (neutropenia, thrombocytopenia, cholestasis). 33% got treatment with val ganciclovir and 33% had sequelae (hearing loss). CONCLUSIONS: CMV congenital infection is still a severe public health issue in developed countries. Most of the cases are mild or asymptomatic even though we should have high clinical suspicion with compatible symptoms and consistent maternal history in order to make an early diagnosis and treatment to prevent or reduce sequelae.

Do measures of social support and social distress share general factors associated with suicidal ideation and attempts?

INTRODUCTION: Aspects of social relationships have variably been associated with suicidal ideation (SI) and suicide attempts (SAs). This study assessed whether social support and social distress measures have general factors versus measure-specific factors that are associated with suicide risk. METHODS: Adults (N = 455, 60.0% female), admitted to psychiatric inpatient units following a recent suicide attempt or active SI, completed assessments of social support (emotional support, instrumental support, friendship, perceived support from significant others, friends, family) and social distress (loneliness, perceived rejection, perceived burdensomeness, thwarted belongingness). Bifactor modeling examined general and specific factors of social support and distress in relation to SI (week prior to hospitalization, via the Beck Scale for SI) and SAs (past 30 days, via the Columbia Suicide Severity Rating Scale). RESULTS: SI was significantly associated with the general social support (B = -1.51), the general social distress (B = 1.67), and the specific perceived burdensomeness (B = 1.57) factors. SAs were significantly associated with the specific Perceived Rejection (OR = 1.05) and Thwarted Belongingness (OR = 0.91) factors. CONCLUSION: General social support and social distress were associated with SI but not recent SAs. Specific social distress factors were also related to SI and SAs controlling for general social distress, suggesting areas for future interventions.

[Experience of patients with immune-mediated inflammatory diseases seen in a multidisciplinary integrated care unit]. / Experiencia de los pacientes con enfermedades inflamatorias inmunomediadas atendidos en una unidad de atención integral multidisciplinar.

OBJECTIVE: To describe the aspects with the greatest impact on the satisfaction of patients treated in a multidisciplinary unit specialising in immune-mediated inflammatory diseases (IMIDs) and to identify areas for improvement in the care model. METHODS: Cross-sectional descriptive study using a satisfaction survey structured in three blocks: sociodemographic variables, functional aspects of the unit and satisfaction with the professionals. Immediate satisfaction was measured on aspects related to the care received, the physical structure and the likelihood of recommending the unit. RESULTS: A total of 168 patients completed the surveys, the mean score of overall satisfaction with the unit was 4.75 (SD:0.4). The regression model showed the relationship between overall satisfaction and unit signage (OR:3.558, p=0.045, 95% CI: 1.027-12.33), coordination between professionals (OR:9.043, p=0.000, 95% CI: 2.79-29.28) and participation in decision making (OR: 44.836, p=0.000, 95% CI: 5.49-365.97). In terms of immediate satisfaction, the overall Net Promoter Score (NPS) was 87 (excellent). The mean score for coordination with Primary Care was 4.54 (SD:0.8) and they scored waiting time to be seen with 4.49 (SD:0.8), so they have been considered an area for improvement The mean score for coordination with Primary Care was 4.54 (SD:0.8) and they scored waiting time to be seen with 4.49 (SD:0.8), so both were considered areas for improvement. CONCLUSIONS: Coordination between intra-centre professionals and patient participation in decision-making explain the excellent level of patient satisfaction. The monitoring of satisfaction has made it possible to implement immediate improvement actions.

Minisatellite diversity supports a recent African origin for modern humans.

In a study of human diversity at a highly variable locus, we have mapped the internal structures of tandem-repetitive alleles from different populations at the minisatellite MS205 (D16S309). The results give an unusually detailed view of the different allelic structures represented on modern human chromosomes, and of the ancestral relationships between them. There was a clear difference in allelic diversity between African and non-African populations. A restricted set of allele families was found in non-African populations, and formed a subset of the much greater diversity seen on African chromosomes. The data strongly support a recent African origin for modern human diversity at this locus.

Development and validation of a real-time PCR assay protocol for the specific detection and quantification of pelagiphages in seawater samples.

Earth is inhabited by numerous adaptations of cellular forms shaped by the persistent scrutiny of natural selection. Thus, as natural selection has fixed beneficial adaptations of functional traits, cellular life has conquered almost all environmental niches on our planet. However, cellular life succumbs in number and genetic diversity to viruses. Among all viruses, phages are highly prevalent in diverse environments, and due to their vast genetic diversity and abundance, their relevant role as significant players in several ecological processes is now fully recognized. Pelagiphages, bacteriophages infecting bacteria of the SAR11 clade, are the most abundant viruses in the oceans. However, the ecological contribution of pelagiphages on populations of Pelagibacterales remains largely underestimated. An essential aspect of estimating the impact of bacteriophages is their absolute and precise quantification, which provides relevant information about the host-virus interactions and the structure of viral assemblages. Consequently, due to its abundance and claimed influence in the biogeochemical cycling of elements, the accurate quantification of pelagiphages results in an essential task. This study describes the development and validation of a sensitive, specific, accurate and reproducible qPCR platform targeting pelagiphages. Moreover, this method allowed the detection and quantification of pelagiphages in the Gulf of California for the first time.

[Impact of covid-19 vaccination on hospitalization in a third-level hospital.] / Impacto de la vacunación frente a la covid-19 sobre la hospitalización en un hospital de tercer nivel.

OBJECTIVE: This study presents information on the evolution of severe cases of SARS-CoV-2 infection that required hospitalization since the beginning of vaccination in Spain. The objective was to know the impact of vaccination against COVID-19 on the hospitalization of patients with SARS-CoV-2 infection, hospital mortality and readmissions for this cause, and to describe the characteristics of vaccinated patients who required admission. METHODS: A retrospective, observational epidemiological study was conducted of all patients admitted with SARS-CoV-2 infection confirmed by a diagnostic test for active infection (PDIA) in a tertiary hospital, from January 2021 to June 2021. The incidence of admissions was calculated based on the vaccination status of the patients and age groups at different times according to the progress of the strategy of vaccination COVID-19. RESULTS: Between December 27, 2020 and June 30, 2021, 1,308 patients with positive PDIA were admitted to the University Hospital of Salamanca, of which 1,167 (89.2%) were not vaccinated, 129 (9.9%) had received one dose of vaccine and 12 (0.9%) were fully vaccinated. Of the latter, none were admitted to the ICU and 2 died. CONCLUSIONS: Vaccination against COVID-19 has contributed to the decrease in hospitalizations, since February 2021, of older and institutionalized people. Fully vaccinated people have a lower risk of admission to the ICU and death. These data, together with the information available on recent cases of new SARS-CoV-2 infections in unvaccinated young people, are in favor of achieving high vaccination coverage of the entire population in the shortest possible time.

OBJETIVO: Este estudio presenta información sobre la evolución de los casos graves de infección SARS-CoV-2 que requirieron hospitalización desde el inicio de la vacunación en España. El objetivo fue conocer el impacto de la vacunación frente a COVID-19 sobre la hospitalización de pacientes con infección SARS-CoV-2, la mortalidad intrahospitalaria y los reingresos por esta causa, y describir las características de los pacientes vacunados que precisaron ingreso. METODOS: Se realizó un estudio epidemiológico observacional retrospectivo, de todos los pacientes ingresados con infección por SARS-CoV-2 confirmada mediante una prueba de diagnóstico de infección activa (PDIA) en un hospital de tercer nivel, de enero de 2021 a junio de 2021. Se calculó la incidencia de ingresos en función del estado vacunal de los pacientes y grupos de edad en diferentes momentos según el avance de la campaña de vacunación. RESULTADOS: Entre el 27 de diciembre de 2020 y el 30 de junio de 2021 ingresaron en el Hospital Universitario de Salamanca 1.308 pacientes con PDIA positiva, de los cuales 1.167 (89,2%) no estaban vacunados, 129 (9,9%) habían recibido una dosis de vacuna y 12 (0,9%) estaban completamente vacunados. De estos últimos, ninguno ingresó en UCI y 2 fallecieron. CONCLUSIONES: La vacunación frente a COVID-19 ha contribuido al descenso de las hospitalizaciones desde el mes de febrero de 2021, sobre todo en personas mayores e institucionalizadas. Las personas completamente vacunadas parecen tener menor riesgo de ingreso en UCI y fallecimiento. Estos datos, junto con la información disponible de los casos recientes de nuevas infecciones por SARS-CoV-2 en personas jóvenes no vacunadas, están a favor de conseguir una cobertura vacunal elevada de toda la población en el menor tiempo posible.