Mitral bioprosthesis early dysfunction treated with transapical valvuloplasty during V-A ECMO.

We report the case of a 61-year-old male who had complications with a mitral valve (MV) bioprosthesis replacement by post-cardiotomy shock leading to VA ECMO implantation. The patient suffered early bioprosthetic valve failure owing to early thrombosis. The complication was successfully treated with a MV bioprosthesis transapical balloon valvuloplasty that restored normal leaflet mobility.

Process Development of a Macrocyclic Peptide Inhibitor of PD-L1.

This article outlines the process development leading to the manufacture of 800 g of BMS-986189, a macrocyclic peptide active pharmaceutical ingredient. Multiple N-methylated unnatural amino acids posed challenges to manufacturing due to the lability of the peptide to cleavage during global side chain deprotection and precipitation steps. These issues were exacerbated upon scale-up, resulting in severe yield loss and necessitating careful impurity identification, understanding the root cause of impurity formation, and process optimization to deliver a scalable synthesis. A systematic study of macrocyclization with its dependence on concentration and pH is presented. In addition, a side chain protected peptide synthesis is discussed where the macrocyclic protected peptide is extremely labile to hydrolysis. A computational study explains the root cause of the increased lability of macrocyclic peptide over linear peptide to hydrolysis. A process solution involving the use of labile protecting groups is discussed. Overall, the article highlights the advancements achieved to enable scalable synthesis of an unusually labile macrocyclic peptide by solid-phase peptide synthesis. The sustainability metric indicates the final preparative chromatography drives a significant fraction of a high process mass intensity (PMI).

Greenhouse gases capture applying impregnated silica with ionic liquids, deep eutectic solvents, and natural deep eutectic solvents.

The development of technologies to capture greenhouse gases (GHGs) like carbon dioxide (CO2) and nitrous oxide (N2O) is vital for climate change mitigation. Ionic liquids (ILs), deep eutectic solvents (DES), and natural deep eutectic solvents (NADES) are promising absorbents to abate GHGs emissions. However, their high viscosity limits the gas-liquid contact, as consequence of the mass transfer. To overcome this, their impregnation onto porous silica gel has been carried out, increasing the gas-liquid contact area. The present study analyzes the effect of size particle of silica gel impregnated with ILs, DES, and NADES over the CO2 and N2O capture at atmospheric conditions. The degree of impregnation of silica particles was determined by thermogravimetric analysis (TGA). The identification of functional groups present on the surface of silica, ILs, DES, and NADES was performed using Fourier-transform infrared spectroscopy (FTIR), and their crystalline structure was determined by X-ray diffraction (XRD). The partition coefficient of CO2 and N2O between gas and ILs, DES, and NADES was determined by a static headspace method. Results show that the degree of solvent impregnation on silica gel ranged from 36.8 to 43.0% w/w, the partition coefficient of CO2 in the impregnated silica varied from 0.005 to 0.067, and for N2O, from 0.005 to 0.032. This suggests that impregnated particles have a greater affinity for N2O compared to CO2. Using impregnated particles requires only 40% of the bulk solvent to achieve a similar GHG capture capacity compared to using bulk solvents.

Mechanistic studies to understand peak tailing due to sulfinic acid- and carboxylic acid-silanophilic interactions in reversed-phase liquid chromatography.

Silanophilic interactions are a primary contributor to peak tailing of acidic pharmaceutical compounds, thus a thorough understanding is especially important for reversed-phase liquid chromatography (RPLC) method development. Herein, a sulfinic acid compound that exhibited severe peak tailing in RPLC with acidic mobile phases was carefully studied. Results indicated that the neutral protonated form of the sulfinic acid is involved in the strong interaction that leads to peak tailing, but that tailing can be mitigated with a blocking effect achieved through use of acetic acid modifier in the mobile phase. Peak tailing was also observed with other structurally-similar sulfinic acids and carboxylic acids but was, in general, less severe with the latter. The Hydrophobic Subtraction Model (HSM) was applied to six commercial C18 columns that exhibited different tailing behaviors for the sulfinic acid compound in attempts to identify key sites of interaction within the stationary phase. A combination of heated acid column wash experiments and density functional theory (DFT) calculations indicate that the differential interactions of the acids with vicinal silanol pairs in the stationary phase play a major role in peak tailing.

High biosorption of cationic dye onto a novel material based on paper mill sludge.

The valorization of paper mill sludge (PMS) is the main goal of this study. The emissions of PMS continue to increase at global scale, especially from packaging paper and board sectors. The raw sludge was used to prepare an adsorbent to remove toxic pollutants from wastewater, the methylene blue (MB), an organic dye. Firstly, the physico-chemical characterization of PMS was done determining the crystalline phases of PMS fibers, the content of main elements, and the pH zero point charge, which was determined at around pH 7. The adsorption of MB on PMS powder was studied at 18 °C with an agitation of 200 rpm, being the best operating conditions 30 min of contact time, 250 mg L-1 of initial MB concentration and 0.05 g in 25 mL of adsorbent dose. Experimental data of MB adsorption was fitted to Langmuir and Freundlich isotherm equations. The Langmuir model was more accurate for the equilibrium data of MB adsorption at pH 5.1. The PFOM and PSOM were adjusted to experimental adsorption kinetics data, being PSOM, which describes better the MB adsorption by PMS powder. This was confirmed by calculating the maximum adsorption capacity with PSOM, which was 42.7 mg g-1, being nearly similar of the experimental value of 43.5 mg g-1. The analysis of adsorption thermodynamics showed that the MB was adsorbed exothermically with a ΔH0 = - 20.78 kJ mol-1, and spontaneously with ΔG0 from - 0.99 to - 6.38 kJ mol-1 in the range of temperature from 291 to 363 K, respectively. These results confirm that the sludge from paper industry can be used as biosorbent with remarkable adsorption capacity and low cost for the treatment of wastewater. PMS can be applied in the future for the depollution of the effluents from the textile industry, which are highly charged with dyes.

Development of a Crystallization-Induced Diastereomer Transformation of Oxime Isomers for the Asymmetric Synthesis of (1S,6R)-3,9-Diazabicyclo[4.2.1]nonane.

Herein we report a practical crystallization-induced diastereomer transformation (CIDT) of oxime isomers for the scalable asymmetric synthesis of the bicyclic diamine (1S,6R)-3,9-diazabicyclo[4.2.1]nonane derivative that serves as a valuable building block in medicinal chemistry. The developed approach utilizes (S)-phenylethylamine as a chiral auxiliary handle for CIDT, and the starting nortropinone derivative is prepared in one step from commercially available materials. The resulting E-oxime is subjected to a stereospecific Beckmann rearrangement, followed by reduction of the resulting lactam with LiAlH4 to afford the monoprotected (1S,6R)-3,9-diazabicyclo[4.2.1]nonane derivative. The development of the CIDT and understanding of the mechanistic implications leading to the high selectivity are reported.

Stark control of electrons across the molecule-semiconductor interface.

Controlling matter at the level of electrons using ultrafast laser sources represents an important challenge for science and technology. Recently, we introduced a general laser control scheme (the Stark control of electrons at interfaces or SCELI) based on the Stark effect that uses the subcycle structure of light to manipulate electron dynamics at semiconductor interfaces [A. Garzón-Ramírez and I. Franco, Phys. Rev. B 98, 121305 (2018)]. Here, we demonstrate that SCELI is also of general applicability in molecule-semiconductor interfaces. We do so by following the quantum dynamics induced by non-resonant few-cycle laser pulses of intermediate intensity (non-perturbative but non-ionizing) across model molecule-semiconductor interfaces of varying level alignments. We show that SCELI induces interfacial charge transfer regardless of the energy level alignment of the interface and even in situations where charge exchange is forbidden via resonant photoexcitation. We further show that the SCELI rate of charge transfer is faster than those offered by resonant photoexcitation routes as it is controlled by the subcycle structure of light. The results underscore the general applicability of SCELI to manipulate electron dynamics at interfaces on ultrafast timescales.

Co-Fermentation of Agri-Food Residues Using a Co-Culture of Yeasts as a New Bioprocess to Produce 2-Phenylethanol.

Whey is a dairy residue generated during the production of cheese and yogurt. Whey contains mainly lactose and proteins, contributing to its high chemical oxygen demand (COD). Current environmental regulations request proper whey disposal to avoid environmental pollution. Whey components can be transformed by yeast into ethanol and biomolecules with aroma and flavor properties, for example, 2-phenyethanol (2PE), highly appreciated in the industry due to its organoleptic and biocidal properties. The present study aimed to valorize agri-food residues in 2PE by developing suitable bioprocess. Cheese whey was used as substrate source, whereas crab headshells, residual soy cake, and brewer's spent yeast (BSY) were used as renewable nitrogen sources for the yeasts Kluyveromyces marxianus and Debaryomyces hansenii. The BSYs promoted the growth of both yeasts and the production of 2PE in flask fermentation. The bioprocess scale-up to 2 L bioreactor allowed for obtaining a 2PE productivity of 0.04 g2PE/L·h, twofold better productivity results compared to the literature. The bioprocess can save a treatment unit because the whey COD decreased under the detection limit of the analytical method, which is lower than environmental requirements. In this way, the bioprocess prevents environmental contamination and contributes to the circular economy of the dairy industry.

Growth patterns in patients with mucopolysaccharidosis VII.

Objective: This study assessed growth patterns in patients with mucopolysaccharidosis (MPS) VII before enzyme replacement therapy. Methods: Height, weight, and body mass index (BMI) measurements and Z-scores from patients from three clinical studies were compared with those from CDC healthy population growth charts. Relationships with age/sex and history of non-immune hydrops fetalis (NIHF) were assessed by linear regression and ANOVA, respectively. Results: Among 20 enrolled patients with MPS VII, height Z-scores were near normal until 1 year of age but declined thereafter, particularly among males. There was no consistent pattern in weight Z-score. BMI Z-scores were above normal and increased slightly with age among males and were slightly below normal among females. Male patients with a history of NIHF had greater declines in height and weight Z-scores over time versus males without history of NIHF. There was no clear effect of NIHF history on height and weight Z-scores in female patients. Conclusions: In patients with MPS VII, declines in height Z-score began early in life, particularly among males, while changes in BMI varied by sex. Patients with MPS VII and a history of NIHF had greater declines in height Z-score with age than did patients without a history of NIHF.Clinical trial registration: This retrospective analysis included patients enrolled in an open-label phase 2 study (UX003-CL203; ClinicalTrials.gov, NCT02418455), a randomized, placebo-controlled, blind-start phase 3 study (UX003-CL301; ClinicalTrials.gov, NCT02230566), or its open-label, long-term extension (UX003-CL202; ClinicalTrials.gov, NCT02432144). Requests for individual de-identified participant data and the clinical study report from this study are available to researchers providing a methodologically sound proposal that is in accordance with the Ultragenyx data sharing commitment. To gain access, data requestors will need to sign a data access and use agreement. Data will be shared via secured portal. The study protocol and statistical analysis plan for this study are available on the relevant clinical trial registry websites with the tabulated results.

Heart transplant in a Sars-CoV-2 positive recipient: Management protocol of the world's first case.

The advent of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in China at the end of 2019 has developed into a global outbreak, and COVID- 19 is an ongoing major public health issue. During the pandemic, transplant programs had to devise strategies to deal with the possibility of COVID-19-positive donors and recipients. We describe the case of a heart transplant recipient who tested positive with the SARS- CoV2 swab upon admission to our Unit of Cardiac Surgery when a suitable donor became available. Given his clinical status of end-stage heart failure and the absence of imaging and clinical signs suggestive of COVID-19, and his having been vaccinated with three doses, we decided to proceed with the transplant.

Triheptanoin for the treatment of long-chain fatty acid oxidation disorders: Final results of an open-label, long-term extension study.

Long-chain fatty acid oxidation disorders (LC-FAODs) result in life-threatening energy metabolism deficiencies/energy source depletion. Triheptanoin is an odd-carbon, medium chain triglyceride (that is an anaplerotic substrate of calories and fatty acids) for treating pediatric and adult patients with LC-FAODs. Study CL202 (NCT02214160), an open-label extension study of study CL201 (NCT01886378), evaluated the long-term safety/efficacy of triheptanoin in patients with LC-FAODs (N = 94), including cohorts who were triheptanoin naïve (n = 33) or had received triheptanoin in study CL201 (n = 24) or in investigator-sponsored trials/expanded access programs (IST/EAPs; n = 37). Primary endpoint was the annualized rate of LC-FAOD major clinical events (MCEs; rhabdomyolysis, hypoglycemia, cardiomyopathy). Mean ± standard deviation (SD) triheptanoin treatment durations were 27.4 ± 19.9, 46.9 ± 13.6, and 49.6 ± 21.4 months for the triheptanoin-naïve, CL201 rollover, and IST/EAP cohorts, respectively. In the triheptanoin-naïve cohort, median (interquartile range [IQR]) MCE rate significantly decreased from 2.00 (0.67-3.33) events/patient/year pre-triheptanoin to 0.28 (0.00-1.43) events/patient/year with triheptanoin (p = 0.0343), a reduction of 86%. In the CL201 rollover cohort, mean ± SD MCE rate significantly decreased from 1.76 ± 1.64 events/patient/year pre-triheptanoin to 1.00 ± 1.00 events/patient/year with triheptanoin (p = 0.0347), a reduction of 43%. In the IST/EAP cohort, mean ± SD MCE rate was 1.40 ± 2.37 (median [IQR] 0.57 [0.00-1.67]) events/patient/year with triheptanoin. Safety data were consistent with previous observations. Treatment-related treatment-emergent adverse events (TEAEs) occurred in 68.1% of patients and were mostly mild/moderate in severity. Five patients had seven serious treatment-related TEAEs; all resolved. Our results confirm the long-term efficacy of triheptanoin for patients with LC-FAOD.

Dental care and risk of developing severe COVID-19 / Atención odontológica y el riesgo de complicación por COVID-19

RESUMEN Durante la pandemia por la COVID-19 la atención odontológica fue recomendada solo en casos de urgencia y dolor. La reducción de citas dentales puede afectar la economía de los dentistas, principalmente la de aquellos que no cuentan con seguridad financiera. Los odontólogos por necesidades económicas requieren brindar atención a pesar del riesgo de ser infectados por SARS-COV-2. Objetivo : Describir la frecuencia de la atención odontológica y el riesgo de complicación por COVID-19 en odontólogos de Ixtlahuaca, Estado de México, México. Material y métodos : Estudio transversal, muestreo no probabilístico desarrollado desde agosto hasta septiembre de 2020. Se aplicó un cuestionario por redes sociales para identificar la frecuencia de la atención odontológica. Resultados: La muestra estuvo conformada por 121 odontólogos; el promedio de edad fue de 32,3 años. La mayor parte de la muestra estuvo conformada por mujeres (74,4 %). Los odontólogos mostraron un riesgo medio a desarrollar complicaciones por COVID-19 (92,5 %). Los odontólogos de práctica privada realizaron más tratamientos no urgentes durante el semáforo epidemiológico rojo y naranja, mostrando diferencias estadísticamente significativas (p ≤ 0,05). El 30 % de la muestra presentó un peso no saludable. Conclusiones : Los odontólogos tienen un riesgo medio a enfermar gravemente por COVID-19. El riesgo se encuentra asociado al peso no saludable. Los odontólogos realizaron tratamientos no urgentes a pesar de las recomendaciones gubernamentales. Los profesionales de práctica privada realizaron una mayor cantidad de tratamientos no urgentes. Los dentistas brindan atención a pesar del riesgo epidemiológico por COVID-19 debido a las necesidades económicas.

ABSTRACT During the COVID-19 pandemic, dental care was recommended only in urgent and severe pain cases. Reduced dental appointments may affect the financial situation of dentists, especially those who are not financially secure. Due to economic necessity, dentists are required to provide care despite the risk of being infected with SARS-COV-2. Objective: To describe the frequency of dental care and the risk of complications due to COVID-19 among dentists in Ixtlahuaca, State of Mexico, Mexico. Material and methods: Cross-sectional study, non-probabilistic sampling carried out from August to September 2020. A survey was carried out through social networks to identify the frequency of dental care. Results: The sample consisted of 121 dentists with an average age of 32.3 years. Women comprised most of the sample (74.4%). Dentists had a medium risk of suffering complications due to COVID-19 (92.5%). Private practice dentists performed more non-urgent treatments during the red and orange epidemiological risk periods, showing statistically significant differences (p≤0.05). Unhealthy weight was present in 30% of the sample. Conclusions: Dentists have a medium risk of becoming seriously ill from COVID-19. The risk is associated with unhealthy weight. Dentists performed non-urgent treatments despite government recommendations. Private practitioners performed a greater number of non-urgent treatments. Dentists provide care despite epidemiological risk related to COVID-19 due to economic necessity.

Augmentation in the repair of traumatic patellar tendon ruptures. A novel mechanical and biological construct: Technical note.

Patellar tendon ruptures are infrequent and potentially disabling injuries. These injuries are usually repaired with transosseous suture tunnels. However, this technique can produce a significant gap formation and prolonged postoperative immobilization. Although several techniques have been described to improve the integrity of the repair, the surgical technique of choice is a matter of debate especially when there is tissue loss due to high-energy trauma. This study aims to evaluate the clinical outcomes of patients with acute patellar tendon ruptures due to high-energy trauma treated with a novel construct configuration that includes a suture anchor and a figure-of-eight augmentation with hamstring autograft with medial and lateral reinforcement. To determine the clinical outcomes the International Knee Documentation Committee (IKDC) score was obtained pre-surgery and at 12 months of follow-up. A total of six patients were recruited, with a median age of 27.5 years, five of these were male. Three lesions were in the proximal pole of the tendon, two were mid-substance and one was in the junction with tibial tuberosity. The IKDC clinical score significantly increased from pre-surgery to the 12-month follow-up with a median difference of 32.8 (95% CI, 19.5-42.6, p = 0.0313). Likewise, the patients presented a post-surgery quadriceps strength level with a median of 5/5. All patients had full active knee extension with a median of 0-120°. There was no statistical difference in the range of motion comparing the surgical knee to the contralateral knee (p = 0.6883). No patient presented any type of reintervention or complication during the follow-up period. The configuration of the construct presented in the technique had not been reported before in the literature and combines the advantages of the use of suture anchors and biological augmentation with lateral and medial reinforcement. This technique may be useful in patients with traumatic injuries with and without loss of tissue. Although it is a small series with concomitant injuries, satisfactory clinical results were presented during follow-up.

Mi Gente, Nuestra Salud: Protocol for a People's Movement for Health Ownership.

BACKGROUND: Community-based participatory research (CBPR) is an increasingly recognized approach to address health inequities. Although in CBPR all processes occur within the community context, its diagrammatic model places the intervention/research outside of the community rather than conceptualizing it as an event in a complex web of system components. OBJECTIVES: We sought to 1) introduce a systems-oriented community ownership conceptual framework that integrates a systems perspective with CBPR and 2) to describe an application of this framework in the form of the Mi Gente, Nuestra Salud initiative, a research-based, action-oriented collaboration between Cal Poly investigators and community partners in Santa Maria and Guadalupe, California. METHODS: We conducted a stocktake of community assets and partnerships in Santa Maria and Guadalupe, among California's poorest and most medically underserved cities; created marketing materials; launched the initiative in December 2020; and collected survey and interview data on community health concerns. An advisory board guides direction of the work. Activities are intended to affect partnerships (who is involved in actions and decisions) and processes (what actions will be taken), as well as resources (e.g., building human and social capital by changing narratives of local, historically rooted power dynamics and offering peer learning opportunities on advocacy and health care interactions). Implementation challenges within this framework are also discussed. CONCLUSIONS: By de-centering specific interventions and conceptualizing them as single events in a complex web, our system-oriented community ownership model brings the focus back to the system itself, and to system-based processes and solutions, while still guided by CBPR principles.

New dating of the Matalascañas footprints provides new evidence of the Middle Pleistocene (MIS 9-8) hominin paleoecology in southern Europe.

Hominin footprints were recently discovered at Matalascañas (Huelva; South of Iberian Peninsula). They were dated thanks to a previous study in deposits of the Asperillo cliff to 106 ± 19 ka, Upper Pleistocene, making Neandertals the most likely track-makers. In this paper, we report new Optically Stimulated Luminescence dating that places the hominin footprints surface in the range of 295.8 ± 17 ka (MIS 9-MIS 8 transition, Middle Pleistocene). This new age implies that the possible track-makers are individuals more likely from the Neandertal evolutionary lineage. Regardless of the taxon attributed to the Matalascañas footprints, they supplement the existing partial fossil record for the European Middle Pleistocene Hominins being notably the first palaeoanthropological evidence (hominin skeleton or footprints) from the MIS 9 and MIS 8 transition discovered in the Iberian Peninsula, a moment of climatic evolution from warm to cool. Thus, the Matalascañas footprints represent a crucial record for understanding human occupations in Europe in the Pleistocene.

Amination of Nitro-Substituted Heteroarenes by Nucleophilic Substitution of Hydrogen.

An open-air method for the transition metal-free direct amination of nitro(hetero)arenes by anilines is disclosed. In this methodology, an aromatic C-H bond is substituted via oxidative nucleophilic aromatic substitution of hydrogen (ONSH). Density functional theory calculations and mechanistic studies support a dianion pathway with oxidation by molecular oxygen as the rate-limiting step.