TRP14 is the rate-limiting enzyme for intracellular cystine reduction and regulates proteome cysteinylation.

It has remained unknown how cells reduce cystine taken up from the extracellular space, which is a required step for further utilization of cysteine in key processes such as protein or glutathione synthesis. Here, we show that the thioredoxin-related protein of 14 kDa (TRP14, encoded by TXNDC17) is the rate-limiting enzyme for intracellular cystine reduction. When TRP14 is genetically knocked out, cysteine synthesis through the transsulfuration pathway becomes the major source of cysteine in human cells, and knockout of both pathways becomes lethal in C. elegans subjected to proteotoxic stress. TRP14 can also reduce cysteinyl moieties on proteins, rescuing their activities as here shown with cysteinylated peroxiredoxin 2. Txndc17 knockout mice were, surprisingly, protected in an acute pancreatitis model, concomitant with activation of Nrf2-driven antioxidant pathways and upregulation of transsulfuration. We conclude that TRP14 is the evolutionarily conserved enzyme principally responsible for intracellular cystine reduction in C. elegans, mice, and humans.

Interaction of C60 with Methylammonium Lead Iodide Perovskite Surfaces: Unveiling the Role of C60 in Surface Engineering.

Understanding the interaction between fullerene (C60) and perovskite surfaces is pivotal for advancing the efficiency and stability of perovskite solar cells. In this study, we investigate the adsorption behavior of C60 on methylammonium lead iodide (MAPbI3) surfaces using periodic density functional theory calculations. We explore various surface terminations and defect configurations to elucidate the influence of surface morphology on the C60-perovskite interaction, computing the adsorption energy and transfer of charge. Our results reveal distinct adsorption energies and charge transfer mechanisms for different surface terminations, shedding light on the role of surface defects in modifying the electronic structure and stability of perovskite materials. Furthermore, we provide insights into the potential of C60 to passivate surface defects, playing a relevant role in the surface reconstruction after the formation of defects. This comprehensive understanding of C60-perovskite interactions offers valuable guidelines about the role of fullerenes on surface structure and reconstruction.

Prevalence and genetic diversity of azole-resistant Malassezia pachydermatis isolates from canine otitis and dermatitis: A 2-year study.

Despite previous reports on the emergence of Malassezia pachydermatis strains with decreased susceptibility to azoles, there is limited information on the actual prevalence and genetic diversity of azole-resistant isolates of this yeast species. We assessed the prevalence of azole resistance in M. pachydermatis isolates from cases of dog otitis or skin disease attended in a veterinary teaching hospital during a 2-year period and analyzed the ERG11 (encoding a lanosterol 14-α demethylase, the primary target of azoles) and whole genome sequence diversity of a group of isolates that displayed reduced azole susceptibility. Susceptibility testing of 89 M. pachydermatis isolates from 54 clinical episodes (1-6 isolates/episode) revealed low minimum inhibitory concentrations (MICs) to most azoles and other antifungals, but 11 isolates from six different episodes (i.e., 12.4% of isolates and 11.1% of episodes) had decreased susceptibility to multiple azoles (fluconazole, itraconazole, ketoconazole, posaconazole, ravuconazole, and/or voriconazole). ERG11 sequencing of these 11 azole-resistant isolates identified eight DNA sequence profiles, most of which contained amino acid substitutions also found in some azole-susceptible isolates. Analysis of whole genome sequencing (WGS) results revealed that the azole-resistant isolates from the same episode of otitis, or even different episodes affecting the same animal, were more genetically related to each other than to isolates from other dogs. In conclusion, our results confirmed the remarkable ERG11 sequence variability in M. pachydermatis isolates of animal origin observed in previous studies and demonstrated the value of WGS for disentangling the epidemiology of this yeast species.

We analyzed the prevalence and diversity of azole-resistant Malassezia pachydermatis isolates in a veterinary hospital. A low prevalence of multi-azole resistance (c.10% of isolates and cases) was found. Whole genome and ERG11 sequencing of resistant isolates revealed remarkable genetic diversity.

Femoral Coronal Malalignment is Associated With Failure in Mobile-Bearing Medial Unicompartmental Knee Arthroplasty.

BACKGROUND: Femur-first (FF) technique for mobile-bearing medial unicompartmental knee arthroplasty (UKA) has been described as an alternative to tibia-first (TF) technique. The aim of this study was to compare the radiographic results in UKAs using FF or TF techniques and their influence on failure rates. METHODS: We retrospectively reviewed 288 UKAs with a minimum 2-year follow-up. There were 147 knees in the TF and 141 knees in the FF cohorts. Alignment parameters and overhang were assessed as outliers and far outliers. The mean follow-up was 6 years (range, 2 to 16), the mean age was 63 years (range, 27 to 92), and 45% of patients were women. Univariate and multivariate statistical analyses were carried out with Cox regression models. RESULTS: There were 13 and 6 revisions in the TF and FF cohorts, respectively. The FF had lower rates of femoral coronal alignment (FCA) or femoral sagittal alignment outliers compared to the TF (5.7% versus 19%, P = .011). Tibial coronal alignment and tibial sagittal alignment did not significantly differ between the techniques (22.7% in FF versus 29.9% in TF, P = .119). Overhang outliers did not differ significantly between the groups. Younger age was associated with a higher revision rate (P = .006), while FF versus TF, sex, body mass index, and postoperative mechanical axis did not show statistically significant associations. In multivariate analysis, FCA outliers and younger age were significantly associated with revision. CONCLUSIONS: The FF technique in mobile-bearing UKA resulted in fewer FCA outliers compared to TF. Despite improved knee alignment with the FF technique, FCA outliers and younger age were associated with a higher revision rate, independent of technique.

The Frank Stinchfield Award: Assembly and Dissociation Forces Differ Between Commonly Used Dual Mobility Implants: A Biomechanical Study.

BACKGROUND: Intraprosthetic dissociation (IPD) is a complication unique to dual mobility (DM) implants where the outer polyethylene head dissociates from the inner femoral head. Increasing reports of IPD at the time of closed reduction of large head DM dislocations prompted this biomechanical study evaluating the assembly and dissociation forces of DM heads. METHODS: We tested 17 polyethylene DM heads from 5 vendors. Of the heads, 12 were highly cross-linked polyethylene (4 vendors) and 5 were infused with vitamin E (2 vendors). Heads were between 46 and 47 mm in diameter, accepting a 28 mm-inner ceramic head. Implants were assembled and disassembled using a servohydraulic machine that recorded the forces and torques applied during testing. Dissociation was tested via both axial pull-out and lever-out techniques, where lever-out simulated stem-on-acetabular component impingement. RESULTS: The initial maximum assembly force was significantly different between all vendors (P < .01) and decreased for all implants with subsequent assembly. Vendor 4-E (Link with vitamin E) heads required the highest assembly force (1,831.9 ± 81.95 N), followed by Vendor 3 (Smith & Nephew), Vendor 5 (DePuy Synthes), Vendor 1-E (Zimmer Biomet with vitamin E), Vendor 2 (Stryker), and Vendor 1 (Zimmer Biomet Arcom). Vendor 4-E implants showed the greatest dissociation resistance in both pull-out (2,059.89 N, n = 1) and lever-out (38.95 ± 2.79 Nm) tests. Vendor 1-E implants with vitamin E required higher assembly force, dissociation force, and energy than Vendor 1 heads without vitamin E. CONCLUSIONS: There were notable differences in DM assembly and dissociation forces between implants. Diminishing force was required for assembly with each additional trial across vendors. Vendor 4-E DM heads required the highest assembly and dissociation forces. Vitamin E appeared to increase the assembly and dissociation forces. Based on these results, DM polyethylene heads should not be reimplanted after dissociation, and there may be a role for establishing a minimum dissociation energy standard to minimize IPD risk.

Total knee replacement with an accelerometer-based, hand-held navigation system improves knee alignment: reliable in all patients.

BACKGROUND: Achieving adequate alignment has traditionally been an important goal in total knee arthroplasty to achieve long-term implant survival. While accelerometer-based hand-held navigation systems (ABN) has been introduced as a way to achieve alignment, there is a limited body of evidence on its accuracy, especially in patients under 65 years with differing etiologies for knee arthritis. This study aimed to assess the precision of a specific ABN system in restoring the mechanical axis and report surgical variables and complications, with particular attention to younger patients. METHODS: We conducted a retrospective review of 310 primary TKA performed with ABN from May 2016 to February 2021. The mean patient age was 67.4 (SD 8.9) years, with 43% under 65 years and mean body mass index of 33.2 (SD 6.8). The average surgical time was 96.8 min (57-171) and the average follow-up was 3.3 years (1.9-6.7). Data regarding length of stay, pain, range of motion (ROM), complications, and reinterventions were collected from the institutional joint arthroplasty registry and the medical records. Preoperative mechanical axis measurements and postoperative radiological data, including mechanical axis, component alignment and mechanical alignment outliers were analyzed. RESULTS: The mean preoperative mechanical axis was 175.4° (SD 7.6), with 248 knees (80%) in preoperative varus. The mean postoperative mechanical axis was 179.5° (SD 1.96) with 98% of knees falling within ± 3° of the neutral mechanical axis. Only 6 knees (2 varus, 4 valgus) fell outside the ± 3° range. And 3 knees (1 varus, 2 valgus) fell outside the ± 5° range. In the sagittal plane, 296 knees (95.5%) knees were within ± 3° of goal of 3 degrees of femoral flexion and 302 (97.4%) knees were within ± 2° of goal 1° of slope for tibial component. Far outliers (alignment outside ± 5° of targeted position) were found in 3 knees. Factors such as posttraumatic arthrosis, previous surgery, presence of retained hardware, and age below 65 years were not associated with increase in alignment outliers and far outliers. No complications related to the navigation system were observed. There were 22 complications and 20 reoperations, including 2 revisions for periprosthetic joint infection and 1 revision for flexion instability. Patients that required knee manipulation achieved an ultimate flexion of 110° (SD 14.1). CONCLUSIONS: The ABN system proved to be user-friendly and accurate in reducing alignment outliers in both coronal and sagittal planes in all patient populations. It offers a straightforward navigation solution while preserving surgeon autonomy and the use of traditional surgical tools. These findings advocate for the integration of this navigation system as a valuable tool to enhance the precision of TKA surgery in all patient groups.

Power Profile during Cycling in World Triathlon Series and Olympic Games.

This study aimed to analyze the power profile (PP) during the cycling segment of international-level triathletes in the World Triathlon Series (WTS) and Olympics and to evaluate the influence of circuit type, race distance (Sprint or Olympic distance) and race dynamics on the development of the cycling leg and the final race position. Four male triathletes participated in the study. Twenty races were analyzed using geolocation technology and power-meter data to analyze PP, race dynamics, and course characteristics. Before the races, incremental tests of volitional exhaustion with gas analysis were performed to determine power intensity zones. Nonparametric Mann-Whitney U tests and correlation analyses were conducted to identify differences and relationships between various variables. A correlation between the time spent above maximal aerobic power (MAP) and dangerous curves per kilometer (r = 0.46; p < 0.05) and bike split result (BSR) (r = -0.50; p < 0.05) was observed. Also, moderate correlation was found between BSR and the final race position (r = 0.46; p < 0.01). No differences were found between sprint and Olympic distance races in any variable. Power output variability, influenced by technical circuit segments, remains the main characteristic in international short-distance races. The results of the present study suggest that the triathletes who are better adapted to intermittent high intensity efforts perform better cycling legs at international high-level races.

A Non Expected Alternative Ni(0) Species in the Ni-Catalytic Aldehyde and Alcohol Arylation Reactions Facilitated by a 1,5-Diaza-3,7-diphosphacyclooctane Ligand.

For decades there were many attempts to dispense with stoichiometric amounts of metal reagents for the synthesis of secondary alcohols. In 2021, the synthetic results of Newman and collaborators pioneered a synthesis still with metals, but not as reactants. Instead, they serverd as catalytic engines. Here we present a description by means of Density Functional Theory calculations of how this process can occur, and an attempt is made to shed light on the mechanism that facilitates the attainment of secondary alcohols, emphasizing the eternal cross-coupling debate of whether the catalytically active species is Ni(0) or they are really taking shortcuts following the course of Ni(II). Effective Orbital analyses give a clear picture. Furthermore, this paper provides insight not only into the nature of the ligands of the metal catalyst but also the role of the base.

Phylogenomic analysis of the genus Rosenbergiella and description of Rosenbergiella gaditana sp. nov., Rosenbergiella metrosideri sp. nov., Rosenbergiella epipactidis subsp. epipactidis subsp. nov., Rosenbergiella epipactidis subsp. californiensis subsp. nov., Rosenbergiella epipactidis subsp. japonicus subsp. nov., Rosenbergiella nectarea subsp. nectarea subsp. nov. and Rosenbergiella nectarea subsp. apis subsp. nov., isolated from floral nectar and insects.

The genus Rosenbergiella is one of the most frequent bacterial inhabitants of flowers and a usual member of the insect microbiota worldwide. To date, there is only one publicly available Rosenbergiella genome, corresponding to the type strain of Rosenbergiella nectarea (8N4T), which precludes a detailed analysis of intra-genus phylogenetic relationships. In this study, we obtained draft genomes of the type strains of the other Rosenbergiella species validly published to date (R. australiborealis, R. collisarenosi and R. epipactidis) and 23 additional isolates of flower and insect origin. Isolate S61T, retrieved from the nectar of an Antirrhinum sp. flower collected in southern Spain, displayed low average nucleotide identity (ANI) and in silico DNA-DNA hybridization (isDDH) values when compared with other Rosenbergiella members (≤86.5 and ≤29.8 %, respectively). Similarly, isolate JB07T, which was obtained from the floral nectar of Metrosideros polymorpha plants in Hawaii (USA) had ≤95.7 % ANI and ≤64.1 % isDDH with other Rosenbergiella isolates. Therefore, our results support the description of two new Rosenbergiella species for which we propose the names Rosenbergiella gaditana sp. nov. (type strain: S61T=NCCB 100789T=DSM 111181T) and Rosenbergiella metrosideri sp. nov. (JB07T=NCCB 100888T=LMG 32616T). Additionally, some R. epipactidis and R. nectarea isolates showed isDDH values<79 % with other conspecific isolates, which suggests that these species include subspecies for which we propose the names Rosenbergiella epipactidis subsp. epipactidis subsp. nov. (S256T=CECT 8502T=LMG 27956T), Rosenbergiella epipactidis subsp. californiensis subsp. nov. (FR72T=NCCB 100898T=LMG 32786T), Rosenbergiella epipactidis subsp. japonicus subsp. nov. (K24T=NCCB 100924T=LMG 32785T), Rosenbergiella nectarea subsp. nectarea subsp. nov. (8N4T = DSM 24150T = LMG 26121T) and Rosenbergiella nectarea subsp. apis subsp. nov. (B1AT=NCCB 100810T= DSM 111763T), respectively. Finally, we present the first phylogenomic analysis of the genus Rosenbergiella and update the formal description of the species R. australiborealis, R. collisarenosi, R. epipactidis and R. nectarea based on new genomic and phenotypic information.

Sugar Concentration, Nitrogen Availability, and Phylogenetic Factors Determine the Ability of Acinetobacter spp. and Rosenbergiella spp. to Grow in Floral Nectar.

The floral nectar of angiosperms harbors a variety of microorganisms that depend predominantly on animal visitors for their dispersal. Although some members of the genus Acinetobacter and all currently known species of Rosenbergiella are thought to be adapted to thrive in nectar, there is limited information about the response of these bacteria to variation in the chemical characteristics of floral nectar. We investigated the growth performance of a diverse collection of Acinetobacter (n = 43) and Rosenbergiella (n = 45) isolates obtained from floral nectar and the digestive tract of flower-visiting bees in a set of 12 artificial nectars differing in sugar content (15% w/v or 50% w/v), nitrogen content (3.48/1.67 ppm or 348/167 ppm of total nitrogen/amino nitrogen), and sugar composition (only sucrose, 1/3 sucrose + 1/3 glucose + 1/3 fructose, or 1/2 glucose + 1/2 fructose). Growth was only observed in four of the 12 artificial nectars. Those containing elevated sugar concentration (50% w/v) and low nitrogen content (3.48/1.67 ppm) were limiting for bacterial growth. Furthermore, phylogenetic analyses revealed that the ability of the bacteria to grow in different types of nectar is highly conserved between closely related isolates and genotypes, but this conservatism rapidly vanishes deeper in phylogeny. Overall, these results demonstrate that the ability of Acinetobacter spp. and Rosenbergiella spp. to grow in floral nectar largely depends on nectar chemistry and bacterial phylogeny.

2D carbon nitride as a support with single Cu, Ag, and Au atoms for carbon dioxide reduction reaction.

The electrochemical conversion of CO2 into value-added chemicals is an important approach to recycling CO2. In this work, we have combined the most efficient metal catalysts for this reaction, namely Cu, Ag, and Au, as single-atom particles dispersed on a two-dimensional carbon nitride support, with the aim of exploring their performance in the CO2 reduction reaction. Here, we report density functional theory computations showing the effect of single metal-atom particles on the support. We found that bare carbon nitride needed a high overpotential to overcome the energy barrier for the first proton-electron transfer, while the second transfer was exergonic. The deposition of single metal atoms enhances the catalytic activity of the system as the first proton-electron transfer is favored in terms of energy, although strong binding energies were found for CO adsorption on Cu and Au single atoms. Our theoretical interpretations are consistent with the experimental evidence that the competitive H2 generation is favored due to the strong CO binding energies. Our computational study paves the road to finding suitable metals that catalyze the first proton-electron transfer in the carbon dioxide reduction reaction and produce reaction intermediates with moderate binding energies, promoting a spillover to the carbon nitride support and thereby serving as bifunctional electrocatalysts.

In vitro activity of fidaxomicin and combinations of fidaxomicin with other antibiotics against Clostridium perfringens strains isolated from dogs and cats.

BACKGROUND: Previous studies have demonstrated that fidaxomicin, a macrocyclic lactone antibiotic used to treat recurrent Clostridioides difficile-associated diarrhea, also displays potent in vitro bactericidal activity against Clostridium perfringens strains isolated from humans. However, to date, there is no data on the susceptibility to fidaxomicin of C. perfringens strains of animal origin. On the other hand, although combination therapy has become popular in human and veterinary medicine, limited data are available on the effects of antibiotic combinations on C. perfringens. We studied the in vitro response of 21 C. perfringens strains obtained from dogs and cats to fidaxomicin and combinations of fidaxomicin with six other antibiotics. RESULTS: When tested by an agar dilution method, fidaxomicin minimum inhibitory concentrations (MICs) ranged between 0.004 and 0.032 µg/ml. Moreover, the results of Etest-based combination assays revealed that the incorporation of fidaxomicin into the test medium at a concentration equivalent to half the MIC significantly increased the susceptibility of isolates to metronidazole and erythromycin in 71.4% and 61.9% of the strains, respectively, and the susceptibility to clindamycin, imipenem, levofloxacin, and vancomycin in 42.9-52.4% of the strains. In contrast, » × MIC concentrations of fidaxomicin did not have any effect on levofloxacin and vancomycin MICs and only enhanced the effects of clindamycin, erythromycin, imipenem, and metronidazole in ≤ 23.8% of the tested strains. CONCLUSIONS: The results of this study demonstrate that fidaxomicin is highly effective against C. perfringens strains of canine and feline origin. Although fidaxomicin is currently considered a critically important antimicrobial that has not yet been licensed for veterinary use, we consider that the results reported in this paper provide useful baseline data to track the possible emergence of fidaxomicin resistant strains of C. perfringens in the veterinary setting.

Training characteristics and performance of two male elite short-distance triathletes: From junior to "world-class".

OBJECTIVE: The sports-science literature lacks data on training and performance characteristics of international elite athletes over multiple seasons. The present case study provided general training characteristics and performance data of two male short-distance triathletes in the Junior, U23, and international Elite categories. METHODS: General training and performance data of two male elite triathletes were described in swimming, cycling, and running segments from the 2015 to 2022 season. The training load was presented using the ECO model while the training intensity distribution (TID) was a triphasic model. RESULTS: Both triathletes increased their performance throughout the seasons. Triathlete A increased his VO2max in cycling by 20.6%, in running by 16.7%. His power at VO2max and his speed at VO2max by 18.9% and 11.0%, respectively. Triathlete B improved his VO2max by 17.8% in cycling, by 16.1% in running and his power at VO2max by 24%, and his speed at VO2max by 14.3%. The triathletes trained on average 14-17 h a week. The TID model was polarized. CONCLUSIONS: To achieve the top international level, it is necessary to consider the following measures: training load progression; improvements in physiological variables; and participation in international events starting from youth categories.

Short-term neurological injury in newborns infants with overcooling in passive hypothermia and transferred to reference hospital in Colombia.

AIM: The aim of the study was to determine whether overcooling (temperature <33°C) during passive hypothermia when transporting neonates with perinatal asphyxia increased the risk of short-term neurological injury. METHODS: A retrospective observational study was performed. Newborns transferred to the LaCardio neonatal unit between January 2021 and April 2022 with moderate and severe perinatal asphyxia and who received passive hypothermia during transport were included. A temperature of <33°C was considered overcooling. A composite outcome of neurological injury was defined by the presence of abnormalities on brain magnetic resonance imaging, video telemetry, seizure before discharge or both. RESULTS: The study included 101 newborns. A total of 18 neonates had a temperature <33°C after transportation. Neurological injuries were present in 21.8% of the temperature <33°C group and 78.2% of the temperature ≥33°C group. Temperature <33°C at the end of transport (aOR 9.2, 95% CI 1.1-77.3) were associated with neurological injury before discharge from the unit. CONCLUSION: During transportation, overcooling in neonates with asphyxia increases the risk of neurological injury before discharge from the neonatal unit. It is important to qualify the transport team with adequate training and equipment for therapeutic hypothermia.

Enhancing the Catalytic Performance of Group I, II Metal Halides in the Cycloaddition of CO2 to Epoxides under Atmospheric Conditions by Cooperation with Homogeneous and Heterogeneous Highly Nucleophilic Aminopyridines: Experimental and Theoretical Study.

Compared to metal-organic complexes and transition-metal halides, group I metal halides are attractive catalysts for the crucial cycloaddition reaction of CO2 to epoxides as they are ubiquitously available and inexpensive, have a low molecular weight, and are not based on (potentially) endangered metals, especially for the case of sodium and potassium. Nevertheless, given their low intrinsic catalytic efficiency, they require the assistance of additional catalytic moieties. In this work, we show that by exploiting the high nucleophilicity of opportunely designed aminopyridines, catalytic systems based on alkaline metals can be formed, which allow the cycloaddition of CO2 to epoxides to proceed under atmospheric pressure at moderate temperatures. Importantly, the aminopyridine nucleophiles can be applied in their heterogenized form, leading to a recyclable catalytic system. An investigation of the reaction mechanism by density functional theory calculations shows that metal halide complexes and nucleophilic pyridines can work as a dual cooperative catalytic system where the use of aminopyridines leads to lower energy barriers for the opening of the epoxide ring, and halide-adducts are involved in the subsequent steps of CO2 insertion and ring closure.

Contrasting effects of nectar yeasts on the reproduction of Mediterranean plant species.

PREMISE: Yeasts are often present in floral nectar and can influence plant fitness directly (independently of pollinators) or indirectly by influencing pollinator visitation and behavior. However, few studies have assessed the effect of nectar yeasts on plant reproductive success or compared effects across different plant species, limiting our understanding of the relative impact of direct vs. indirect effects. METHODS: We inoculated the nectar of six plant species in the field with the cosmopolitan yeast Metschnikowia reukaufii to analyze the direct and indirect effects on female reproductive success over 2 years. The pollinator assemblage for each species was recorded during both flowering years. RESULTS: Direct yeast effects on female fecundity were statistically nonsignificant for all plant species. There were significant indirect, pollinator-mediated effects on fruit production and seed mass for the two species pollinated almost exclusively by bumblebees or hawkmoths, with the direction of the effects differing for the quantity- and quality-related fitness components. There were no consistent effects of the yeast on maternal fecundity for any of the species with diverse pollinator assemblages. CONCLUSIONS: Effects of M. reukaufii on plant reproduction ranged from negative to neutral or positive depending on the plant species. The among-species variation in the indirect effects of nectar yeasts on plant pollination could reflect variation in the pollinator community, the specific microbes colonizing the nectar, and the order of microbial infection (priority effects), determining potential species interactions. Elucidating the nature of these multitrophic plant-pollinator-microbe interactions is important to understand complex processes underlying plant pollination.

Chiral C2 -symmetric bis-thioureas as enzyme mimics in enantioselective Michael addition.

We report herein the synthesis and application of enantiopure C2 -symmetric primary amine-1,3-bis-thiourea organocatalysts in enantioselective conjugate 1,4-Michael addition of carbonyl containing nucleophiles, to nitroalkenes and N-phenylmaleimide, leading to final products in good enantioselectivities (up to 99%) and yields (up to 99%). We propose supramolecular noncovalent interactions within the organocatalyst's cleft between the substrate and the catalyst, via hydrogen bonding. Supramolecular interaction thus lowers the transition state energy mimicking an enzyme. Mechanism underlying our experimental results is supported by theorical calculations.

A novel temporary atrioventricular sequential pacing catheter-Characteristics and first-in-human application.

BACKGROUND: Sequential synchronized atrioventricular (AV) pacing provides enhanced electrophysiologic parameters which contribute to improved hemodynamic parameters and increased cardiac performance to subsequently confer a clinical advantage over traditional ventricular pacing. Current temporary transvenous pacemaker catheters are limited to only one electrode which paces solely the right ventricle, thus lacking the capability to provide the optimal pacing mode. A new multilead pacemaker device was developed in response to the need for improved temporary pacing through the utilization of sequential synchronized atrioventricular pacing (TAVSP). It consists of seven preformed, preshaped nitinol wires electrodes, of which four are for intra-atrial and three for intraventricular positioning and endocardial contact, respectively. Each wire carries a ball tip designed to minimize tissue trauma and provide a high current density for adequate myocardial capture. The device is not yet Food and Drug Administration approved. OBJECTIVE: To present the unique structural components and mechanical properties of a novel sequential synchronized AV pacing device for temporary insertion and to report its first-in-human application with an analysis of the early clinical experience. METHODS: Following a process of development and proof of concept of the novel pacing modality in an animal model which demonstrated feasibility and safety, a series of patients who were candidates for the device application was identified. During left and right heart catheterization, the novel temporary pacing catheter was inserted transvenously and delivered in most patients under fluoroscopy or echocardiography. The catheter was deployed to its target right heart anatomic sites and then activated in an AV sequential mode. The technical aspects, the corresponding clinical utilization, and device performance were documented and analyzed. RESULTS: The series included 10 enrolled subjects. During planned left and right heart catheterization, the novel TAVSP device was inserted transvenously and then delivered and deployed successfully in a timely fashion in all patients. The pacing catheter achieved proper threshold and impedance in all (100%) patients. The performance of all ventricular leads was adequate; however, in 1 (10%) patient poor performance of the atrial leads was detected. The device was successfully retrieved in all patients. No adverse arrhythmia, impaired hemodynamics, or clinical adverse events occurred. No technical difficulties, component failure, or wires thrombosis were detected. All patients sustained the device application without sequala and were discharged home. CONCLUSION: Initial clinical experience with the utilization of a novel TAVSP demonstrates feasibility and safety in humans. The TAVSP modality potentially offers improved pacing capability and subsequent hemodynamic benefits over the current temporary pacing catheters. Further experience with the clinical application of this pacing catheter is warranted.

Validation of an instrument for the evaluation of exchange transfusion (INEXTUS) via an OSCE.

INTRODUCTION: Exchange transfusion is the treatment of choice for patients with severe hyperbilirubinemia who do not respond to phototherapy. This procedure is highly complex and requires substantial expertise to perform, however it´s not done frequently enough to guarantee adequate training. Traditional learning scenarios do not have a space reserved for teaching this procedure or an instrument that fully and objectively evaluates the skills that a professional must acquire.  OBJECTIVES: The purpose was to construct and evaluate the INEXTUS instrument´s validity evidence relevant to internal structure, in a simulated scenario through the performance of an objective structured clinical exam (OSCE).  MATERIALS AND METHODS: The Delphi consensus methodology was utilized to design the instrument; six experts participated through three rounds using the Google Forms platform. The categories and items previously obtained were subjected to validation by nine experts through a dichotomous survey. Prior to data collection, the evaluators were trained through a pilot test with 10 medical students. Subsequently, all residents of a paediatric programme were evaluated through the OSCE methodology in a simulated scenario, with 6 stations, of a clinical case of a new-born with an explicit need for exchange transfusion. During their participation in the scenario, the residents were first evaluated with the instrument developed. Additionally, audio and video filming of all students who participated was performed with the aim of conducting a second evaluation two weeks after the first four evaluators participated. RESULTS: The final INEXTUS instrument consists of 46 subitems grouped into 23 items divided into 6 categories, demonstrating an inter-rater intraclass correlation coefficient of 0.96 (95% CI 0.94, 0.98 p-value < 0.001). For the Fleiss Kappa of the 23 items evaluated, concordance was evaluated for 14 items but could not be determined for the 9 remaining items because all the ratings were equal, either because the items were not performed or they were all performed adequately. Of the 14 items, 9 good scores were obtained (95% CI 0.61 to 0.8; p value < 0.001), and 5 very good scores were obtained (95% CI 0.81 to 1; p value < 0.001). CONCLUSIONS: The INEXTUS instrument evaluates exchange transfusion skills in medical personnel in training in simulated scenarios using the OSCE methodology; it has high validity and reliability and is a high-impact educational tool.

Effect of the Helping Babies Breathe Program on Newborn Outcomes: Systematic Review and Meta-Analysis.

Background and objectives: In low- and middle-income countries, the leading cause of neonatal mortality is perinatal asphyxia. Training in neonatal resuscitation has been shown to decrease this cause of mortality. The program "Helping Babies Breathe" (HBB) is a program to teach basic neonatal resuscitation focused on countries and areas with limited economic resources. The aim of the study was to determine the effect of the implementation of the HBB program on newborn outcomes: mortality and morbidity. Material and Methods: A systematic review was carried out on observational studies and clinical trials that reported the effect of the implementation in low- and middle-income countries of the HBB program on neonatal mortality and morbidity. We carried out a meta-analysis of the extracted data. Random-effect models were used to evaluate heterogeneity, using the Cochrane Q and I2 tests, and stratified analyses were performed by age and type of outcome to determine the sources of heterogeneity. Results: Eleven studies were identified. The implementation of the program includes educational strategies focused on the training of doctors, nurses, midwives, and students of health professions. The poled results showed a decrease in overall mortality (OR 0.67; 95% CI 0.57, 0.80), intrapartum stillbirth mortality (OR 0.62; 95% CI 0.51, 0.75), and first-day mortality (OR 0.70; 95% IC 0.64, 0.77). High heterogeneity was found, which was partly explained by differences in the gestational age of the participants. Conclusions: The implementation of the program HBB in low- and medium-income countries has a significant impact on reducing early neonatal mortality.