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1.
J Emerg Med ; 66(2): 177-183, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38290883

RESUMEN

BACKGROUND: Since the introduction of electric-scooter (e-scooter) mobile applications, there has been a marked increase in e-scooter-related injury. On January 19, 2022, the City of Miami revoked permits to five major mobile applications for violation of safety protocols. OBJECTIVES: The purpose of our study was to assess the effects of this notice on the orthopedic patients seen at our corresponding Level I trauma center. METHODS: Institutional Review Board approval was obtained for this study. A retrospective chart review was performed including all patients with orthopedic injuries at our Level I trauma center between July 19, 2021 and July 19, 2022. These dates include 6 months prior to and after the major e-scooter operators ceased use in Miami. SPSS statistical software version 28.0.0 (SPSS, IBM, Armonk, NY) was utilized for all statistical analysis. RESULTS: There were 2558 patients in the prenotice cohort, and 2492 patients in the postnotice cohort. After the notice, there was a significant decrease in the number of patients that presented to our institution due to injuries caused by e-scooters (2.8% vs. 1.8% patients; p = 0.021). Patients with injuries caused by e-scooters had a significantly lower age (38 vs. 42, respectively; p = 0.034) and were more likely to be male (79.3% vs. 67.4% male, respectively; p = 0.007) than patients with other orthopedic injuries. CONCLUSION: This study demonstrates that the 2022 notice revoking the major mobile application operators from the City of Miami resulted in a significant decrease in the number of orthopedic cases due to e-scooter-related injury at the corresponding Level I trauma center.


Asunto(s)
Traumatismos por Electricidad , Centros Traumatológicos , Humanos , Masculino , Femenino , Estudios Retrospectivos , Accidentes de Tránsito , Dispositivos de Protección de la Cabeza
2.
Arch Orthop Trauma Surg ; 144(6): 2527-2538, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38744693

RESUMEN

INTRODUCTION: Entry point selection, a crucial aspect of femoral antegrade nailing, can impact nail fit and consequently fracture reduction. In adults, the standard entry portals used are the piriformis fossa and the tip of the greater trochanter. Previous systematic reviews comparing the two techniques have not been limited to Randomized Controlled Trials (RCTs) and have not consistently included the same available RCTs. MATERIALS AND METHODS: A systematic search of comparative studies regarding entry portal selection in femoral antegrade nailing was conducted on seven databases. Only Prospective RCTs comparing trochanteric and piriformis entry in the management of trochanteric or diaphyseal femur fractures were eligible for inclusion. RESULTS: Ultimately, only 6 RCTs were found eligible for inclusion. Five of the six included studies reported on operative time. The resulting mean difference (MD) illustrated a significant decrease in operative time by approximately 21.26 min (95% CI - 28.60 to - 13.92, p < 0.001) using trochanteric entry. Fluoroscopy exposure was reported on by four studies, however, only two studies were included in the analysis due to different reporting methods. Trochanteric entry used significantly less fluoroscopy than piriformis entry (MD -50.33 s, 95% CI - 84.441 to - 16.22, p = 0. 004). No significant difference in malalignment rates, delayed union rates, nonunion rates, pain scores, or complication rates was found. CONCLUSION: The significant differences found in operating time and fluoroscopy time align with those in other studies. While we were not able to pool the data on functional outcome scores, none of the included studies found a significant difference in scores by their last follow-up. Both approaches demonstrate comparable functional outcomes and safety profiles, indicating the choice of entry point should be at the discretion of the surgeon based on technique familiarity and fracture characteristics.


Asunto(s)
Clavos Ortopédicos , Fracturas del Fémur , Fijación Intramedular de Fracturas , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Fracturas del Fémur/cirugía , Fémur/cirugía , Fijación Intramedular de Fracturas/métodos , Tempo Operativo
3.
Yeast ; 40(8): 290-302, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-36597618

RESUMEN

Microbial lipids produced from lignocellulose and crude glycerol (CG) can serve as sustainable alternatives to vegetable oils, whose production is, in many cases, accompanied by monocultures, land use changes or rain forest clearings. Our projects aim to understand the physiology of microbial lipid production by oleaginous yeasts, optimise the production and establish novel applications of microbial lipid compounds. We have established methods for fermentation and intracellular lipid quantification. Following the kinetics of lipid accumulation in different strains, we found high variability in lipid formation even between very closely related oleaginous yeast strains on both, wheat straw hydrolysate and CG. For example, on complete wheat straw hydrolysate, we saw that one Rhodotorula glutinis strain, when starting assimilating D-xylosealso assimilated the accumulated lipids, while a Rhodotorula babjevae strain could accumulate lipids on D-xylose. Two strains (Rhodotorula toruloides CBS 14 and R. glutinis CBS 3044) were found to be the best out of 27 tested to accumulate lipids on CG. Interestingly, the presence of hemicellulose hydrolysate stimulated glycerol assimilation in both strains. Apart from microbial oil, R. toruloides also produces carotenoids. The first attempts of extraction using the classical acetone-based method showed that ß-carotene is the major carotenoid. However, there are indications that there are also substantial amounts of torulene and torularhodin, which have a very high potential as antioxidants.


Asunto(s)
Glicerol , Rhodotorula , Biocombustibles , Levaduras , Lípidos , Biomasa
4.
Clin Anat ; 36(2): 291-296, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36482009

RESUMEN

To address anatomy knowledge gaps exacerbated by the education constraints of a new shortened medical school curriculum and the COVID-19 pandemic, the Orthopedic Surgery Interest Group (OSIG) created a novel hybrid anatomy curriculum for students interested in orthopedic surgery. The main objectives were to determine (1) Does this elective supplement to the curriculum improve students' perceived confidence with regard to orthopedic anatomy? (2) What are the students' preferred formats for receiving this elective supplement to the curriculum? To determine this, we used a prospective study design to determine the impact of the OSIG's student-led hybrid anatomy sessions. A survey with a five-point Likert scale (1) Strongly disagree; (2) Disagree; (3) Neither agree nor disagree; (4) Agree; (5) Strongly agree; was used to quantify responses. Chi-squared tests, Fisher's exact tests and T-tests were used when appropriate. Our results show that participants without prior anatomy experience rated the course higher on average when compared with those with prior anatomy experience (4.27 vs. 3.67, respectively; p = 0.168). Most students (88.2%) prefer for anatomy sessions to be held more frequently and 76.4% enjoyed having virtual components. 82.4% of participants reported that this course improved their self-confidence regarding orthopedic anatomy, and 100% would recommend it to other students. Most students enjoyed the course and reported improved self-perceived anatomy knowledge after participating. Medical schools that have a shortened anatomy curriculum can consider using the present study as a model for an optional musculoskeletal anatomy supplement at their institution.


Asunto(s)
Anatomía , COVID-19 , Educación de Pregrado en Medicina , Estudiantes de Medicina , Humanos , Facultades de Medicina , Estudios Prospectivos , Pandemias , COVID-19/prevención & control , Curriculum , Educación de Pregrado en Medicina/métodos , Anatomía/educación
5.
Molecules ; 28(21)2023 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-37959702

RESUMEN

Recent studies have demonstrated the antiproliferative and cytotoxic effects of aza-steroids and steroidal sapogenins on human cancer cell lines. The scientific community has shown a growing interest in these compounds as drug candidates for cancer treatment. In the current work, we report the synthesis of new diosgenin oxime derivatives as potential antiproliferative agents. From (25 R)-5α-spirost-3,5,6-triol (1), a diosgenin derivative, ketones 2, 3, 4, and 9 were obtained and used as precursors of the new oximes. A condensation reaction was carried out between the steroidal ketones (2, 3, 4, and 9) with hydroxylamine hydrochloride in 2,4,6-trimethylpyridine to produce five spirostanic oximes (four of them are not reported before) with a 42-96% yield. Also, a new spirostanic α, ß-unsaturated cyanoketone was synthesized via Beckmann fragmentation using thionyl chloride with a 62% yield. Furthermore, we proposed a reaction mechanism with the aim of explaining such transformation.


Asunto(s)
Antineoplásicos , Diosgenina , Humanos , Cianocetona , Diosgenina/farmacología , Esteroides/farmacología , Antineoplásicos/farmacología , Oximas/farmacología , Cetonas/farmacología
6.
Pharmacology ; 107(11-12): 556-563, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36349790

RESUMEN

BACKGROUND: Intravenous immunoglobulin and subcutaneous immunoglobulin preparations are used to treat primary and secondary immunodeficiencies, as well as autoimmune and inflammatory conditions. SUMMARY: For certain indications, only defined formulations or routes of administration are approved by health authorities. However, for other diseases, there are more options, and treatment decisions may be based on different aspects, such as patient conditions and preferences, pharmacokinetics, or pharmacoeconomic considerations. KEY MESSAGES: Understanding the two different treatment modalities may support the decision-making for the optimal therapeutic option for individual patients. This review summarizes the latest insights into the direct and indirect comparison between the two types of products.


Asunto(s)
Inmunoglobulinas , Síndromes de Inmunodeficiencia , Humanos , Inmunoglobulinas/uso terapéutico , Inmunoglobulinas Intravenosas/uso terapéutico , Síndromes de Inmunodeficiencia/tratamiento farmacológico , Administración Intravenosa
7.
Genomics ; 113(6): 4022-4027, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34648882

RESUMEN

Rhodotorula toruloides is an oleaginous yeast with high biotechnological potential. In order to understand the molecular physiology of lipid synthesis in R. toruloides and to advance metabolic engineering, a high-resolution genome is required. We constructed a genome draft of R. toruloides CBS 14, using a hybrid assembly approach, consisting of short and long reads generated by Illumina and Nanopore sequencing, respectively. The genome draft consists of 23 contigs and 3 scaffolds, with a N50 length of 1,529,952 bp, thus largely representing chromosomal organization. The total size of the genome is 20,534,857 bp and the overall GC content is 61.83%. Transcriptomic data from different growth conditions was used to aid species-specific gene annotation. We annotated 9464 genes and identified 11,691 transcripts. Furthermore, we demonstrated the presence of a potential plasmid, an extrachromosomal circular structure of about 11 kb with a copy number about three times as high as the other chromosomes.


Asunto(s)
Rhodotorula , Transcriptoma , Cromosomas , Anotación de Secuencia Molecular , Rhodotorula/genética
8.
J Surg Orthop Adv ; 31(2): 113-118, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35820098

RESUMEN

Prophylactic radiotherapy (XRT) is a commonly used treatment to decrease heterotopic ossification (HO) in patients with traumatic hip injuries. We conducted a retrospective review of patients at risk for HO who underwent XRT. Of the patients reviewed, 27.3% developed radiographic HO, 11.2% developed symptoms, and 2.0% required resection surgery. Patients were divided into primary (n = 71) and secondary prophylaxis (n = 27) cohorts. In the primary group, 25.0% developed radiographic HO, 5.6% developed symptoms, and 0 required surgery. In the secondary cohort, 33.3% of patients developed new radiographic HO, and 25.9% were symptomatic: four had a Brooker score of 3, and three had a score of 4 (p = 0.03), and 7.4% required surgical resection. (Journal of Surgical Orthopaedic Advances 31(2):113-118, 2022).


Asunto(s)
Fracturas Óseas , Osificación Heterotópica , Fracturas Óseas/complicaciones , Fracturas Óseas/cirugía , Humanos , Osificación Heterotópica/etiología , Osificación Heterotópica/prevención & control , Estudios Retrospectivos , Factores de Riesgo
9.
Mol Cell ; 43(2): 217-28, 2011 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-21777811

RESUMEN

The ClpS adaptor delivers N-end rule substrates to ClpAP, an energy-dependent AAA+ protease, for degradation. How ClpS binds specific N-end residues is known in atomic detail and clarified here, but the delivery mechanism is poorly understood. We show that substrate binding is enhanced when ClpS binds hexameric ClpA. Reciprocally, N-end rule substrates increase ClpS affinity for ClpA(6). Enhanced binding requires the N-end residue and a peptide bond of the substrate, as well as multiple aspects of ClpS, including a side chain that contacts the substrate α-amino group and the flexible N-terminal extension (NTE). Finally, enhancement also needs the N domain and AAA+ rings of ClpA, connected by a long linker. The NTE can be engaged by the ClpA translocation pore, but ClpS resists unfolding/degradation. We propose a staged-delivery model that illustrates how intimate contacts between the substrate, adaptor, and protease reprogram specificity and coordinate handoff from the adaptor to the protease.


Asunto(s)
Proteínas Portadoras/química , Proteínas de Escherichia coli/química , Secuencia de Aminoácidos , Sitios de Unión , Proteínas Portadoras/metabolismo , Cristalografía por Rayos X , Endopeptidasa Clp/química , Endopeptidasa Clp/metabolismo , Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Datos de Secuencia Molecular , Sensibilidad y Especificidad , Especificidad por Sustrato
10.
Proc Natl Acad Sci U S A ; 111(37): E3853-9, 2014 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-25187555

RESUMEN

The ClpS adaptor collaborates with the AAA+ ClpAP protease to recognize and degrade N-degron substrates. ClpS binds the substrate N-degron and assembles into a high-affinity ClpS-substrate-ClpA complex, but how the N-degron is transferred from ClpS to the axial pore of the AAA+ ClpA unfoldase to initiate degradation is not known. Here we demonstrate that the unstructured N-terminal extension (NTE) of ClpS enters the ClpA processing pore in the active ternary complex. We establish that ClpS promotes delivery only in cis, as demonstrated by mixing ClpS variants with distinct substrate specificity and either active or inactive NTE truncations. Importantly, we find that ClpA engagement of the ClpS NTE is crucial for ClpS-mediated substrate delivery by using ClpS variants carrying "blocking" elements that prevent the NTE from entering the pore. These results support models in which enzymatic activity of ClpA actively remodels ClpS to promote substrate transfer, and highlight how ATPase/motor activities of AAA+ proteases can be critical for substrate selection as well as protein degradation.


Asunto(s)
Proteínas Portadoras/metabolismo , Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , Proteolisis , Proteínas Portadoras/química , Endopeptidasa Clp/metabolismo , Escherichia coli/enzimología , Proteínas de Escherichia coli/química , Modelos Moleculares , Proteínas Mutantes/metabolismo , Especificidad por Sustrato
11.
Mol Cell ; 32(3): 406-14, 2008 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-18995838

RESUMEN

The N-end rule targets specific proteins for destruction in prokaryotes and eukaryotes. Here, we report a crystal structure of a bacterial N-end rule adaptor, ClpS, bound to a peptide mimic of an N-end rule substrate. This structure, which was solved at a resolution of 1.15 A, reveals specific recognition of the peptide alpha-amino group via hydrogen bonding and shows that the peptide's N-terminal tyrosine side chain is buried in a deep hydrophobic cleft that pre-exists on the surface of ClpS. The adaptor side chains that contact the peptide's N-terminal residue are highly conserved in orthologs and in E3 ubiquitin ligases that mediate eukaryotic N-end rule recognition. We show that mutation of critical ClpS contact residues abrogates substrate delivery to and degradation by the AAA+ protease ClpAP, demonstrate that modification of the hydrophobic pocket results in altered N-end rule specificity, and discuss functional implications for the mechanism of substrate delivery.


Asunto(s)
Ubiquitina-Proteína Ligasas/química , Ubiquitina-Proteína Ligasas/metabolismo , Secuencia de Aminoácidos , Bacterias/química , Bacterias/metabolismo , Sitios de Unión , Secuencia Conservada , Cristalografía por Rayos X , Células Eucariotas/química , Células Eucariotas/fisiología , Modelos Moleculares , Datos de Secuencia Molecular , Fragmentos de Péptidos/química , Fragmentos de Péptidos/metabolismo , Sensibilidad y Especificidad , Tirosina/química
12.
Plast Reconstr Surg Glob Open ; 12(8): e6087, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39171247

RESUMEN

We report the case of a 43-year-old woman who presented with combined radial, median, and ulnar nerve palsies and a spiral humeral shaft fracture after falling down stairs. Postinjury, the patient did not recover full median, ulnar, and radial nerve function despite aggressive hand therapy. Electrodiagnostic studies and imaging findings were concerning for traction neuropraxia or transection, radial nerve neuroma, and scar encasement of the radial, median, and ulnar nerves. The patient underwent radial, median, ulnar, and musculocutaneous nerve neuroplasty, nerve wrap application, nerve stimulation and laser angiography. Surgical exploration revealed no transection injuries to the median, ulnar, or musculocutaneous nerves. The radial nerve was tethered to the fracture site and enlarged, but no neuroma was observed. Laser angiography demonstrated intact perfusion to all nerves. The patient went on to recover full nerve function. Although isolated radial nerve palsies associated with closed humeral shaft fractures are typically observed initially, management of combined nerve palsies is controversial. This case serves to caution surgeons to perform a thorough neurovascular examination on patients with humeral shaft fractures to identify combined nerve palsies.

13.
Arch Bone Jt Surg ; 12(7): 515-521, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39070876

RESUMEN

Objectives: Acute compartment syndrome of the thigh (CST) is an ongoing challenge for orthopaedic surgeons as the diagnosis is often difficult to establish. Currently, there is a shortage of studies investigating risk factors for the development of thigh compartment syndrome following subtrochanteric and diaphyseal femoral fractures. This study aimed to identify risk factors associated with the development of CST following femoral fractures. Methods: Retrospective review performed in a level one trauma center from January 2011 to December 2020 for all patients with non-pathological acute subtrochanteric or diaphyseal femoral fractures. Variables collected included demographics, injury severity score (ISS) scores, mechanism of injury, classification of femoral fracture, open versus closed injuries, development of compartment syndrome, time to compartment syndrome diagnosis, number of subsequent surgeries, and primary wound closure versus split-thickness skin graft. The statistical analysis of this study included descriptive analysis, simple logistic regression, paired T-test, and Wilcoxon Signed Rank. Results: Thirty-one (7.7%) patients developed thigh compartment syndrome following 403 subtrochanteric or diaphyseal femoral fractures. The mean (SD) age for those who developed CST was 27.35 (8.42). For every unit increase in age, the probability of developing CST decreased. Furthermore, male gender had 18.52 times greater probability of developing CST (P <0.001). AO/OTA 32-C3 and subtrochanteric femoral fracture patterns demonstrated 15.42 (P = 0.011) and 3.15 (P <0.001) greater probability of developing CST, respectively. Patients who presented to the hospital following a motor vehicle accident (MVA) or gunshot wound (GSW) had 5.90 (P= 0.006) and 14.87 (P < 0.001) greater probability of developing CST, respectively. Conclusion: Patients who were male, younger in age, and had a 32-C3 and subtrochanteric femoral fractures were at increased probability of developing CST. High energy trauma also increased the risk of developing CST. A high index of suspicion should be expressed in patients with these risk factors.

14.
J Fungi (Basel) ; 10(8)2024 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-39194873

RESUMEN

Trichoderma spp. are filamentous fungi generally observed in nature, which are widely marketed as biocontrol agents. The secondary metabolites produced have obtained special attention since they possess attractive chemical structures with a broad spectrum of biological activities. In Cuba, the species of Trichoderma have been commercially applied for the control of several phytopathogens to protect agricultural crops, but few studies have been carried out to detect and characterize the production of metabolites with biological activity. The strain Trichoderma harzianum LBAT-53 was subjected to an antifungal in vitro assay against Fusarium oxysporum f.sp. cubense by dual culture and volatile metabolite assays and fermented in PDB under constant agitation conditions. The ethyl acetate crude extract was obtained by liquid-liquid extraction. The fungal extract was investigated for the composition of secondary metabolites through chemical screening and ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) in negative ionization mode. As a result, LBAT-53 showed antagonistic activity in vitro (Class 2) against the pathogen evaluated in direct confrontation (76.9% of inhibition in 10 days) and by volatile metabolites (<40% in 7 days). Furthermore, seven low-molecular-weight phenolic compounds, including chrysophanol, phomarin, endocrocin, and trichophenol A, among others, were identified using UHPLC-ESI-MS/MS. This study is the first work on the characterization of secondary metabolites produced by the commercially applied strain LBAT-53, which is a promising source of bioactive compounds. These results provide a better understanding of the metabolism of this fungus, which is widely used in Cuba as biopesticides in agriculture pest control.

15.
J Orthop ; 44: 66-71, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37700780

RESUMEN

Intro: Simulation-based training has become a valuable new tool in medical education across the country. The Orthopedic Surgery Interest Group (OSIG) at the University of Miami Miller School of Medicine organized a benchtop training workshop known as "Sawbones" to give medical students essential exposure to basic techniques and instruments commonly used in orthopedic surgery. This pilot study seeks to investigate the participating students' perceptions of this workshop as part of a potential longitudinal intervention. Methods: A total of 30 medical students (MS1-MS4) with a documented interest in orthopedic surgery were randomly selected via email invitation to participate in this workshop. Students first had a lecture-based training session with faculty on an overview of screw fixation. Participants then formed groups that were headed by an orthopedic resident or attending and took turns fixing fractures on model bones made of synthetic material. Following the session, students were sent an anonymous Qualtrics survey to assess their satisfaction with the workshop. Results: A total of 22 students (73%), responded to the survey. On a ten-point scale, the average reported interest in orthopedics was 9.2 (SD 0.4). All students (n = 22, 100%) reported that they would like more hands-on orthopedic experiences as a component of their medical education. Nineteen students (86.4%) reported that this training increased their interest in pursuing a career in orthopedic surgery and twenty-one (95.5%) further stated that they would recommend this training to other students. Discussion: Based on the results of this pilot study, Sawbones was promising at engaging students in orthopedics, providing a team environment, and introducing students to orthopedic skills and instrumentation. Providing these sessions in a longitudinal manner could provide opportunities for mentorship and better prepare students for a residency in orthopedics. We recommend a program like Sawbones to better address the lack of Orthopedic exposure in medical school.

16.
Ann Med Surg (Lond) ; 85(11): 5523-5527, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37920654

RESUMEN

Introduction: The impact of anxiety and depression on outcomes in orthopaedic trauma surgery is a topic of growing research interest. Patients and methods: Orthopaedic trauma patients often experience high rates of psychiatric disorders, with anxiety and depression being the most prevalent. Mental health disorders have been shown to increase the risk of negative surgical outcomes and morbidity. This narrative review seeks to summarize the current literature surrounding the impacts of anxiety and depression on orthopaedic trauma surgery outcomes. Discussion: There is a bidirectional relationship between chronic pain and mental health disorders, involving overlapping brain regions and neurotransmitter pathways. Anxiety and depression have been identified as predictors of negative surgical outcomes in orthopaedic trauma patients. Screening tools like the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder Screener-7 (GAD-7), and Medical Outcomes Study 36-item Short Form (SF-36) can assess mental health status and help tailor interventions. Psychological distress, chronic pain, and traumatic limb amputation are factors that contribute to adverse mental health outcomes in orthopaedic trauma patients. Opioid use for pain management is common in orthopaedic surgery, but it can worsen symptoms of depression and lead to dependency. Non-opioid pain management strategies may improve postoperative outcomes by reducing the impact of opioid-exacerbated depression. Conclusion: Mental health interventions, both preoperative and postoperative, are crucial in optimizing surgical outcomes and improving patient quality of life. Multidisciplinary approaches that address both physical and mental health are recommended for orthopaedic trauma patients. Further research is needed to develop effective interventions for improving mental health outcomes in this patient population.

17.
Biotechnol Biofuels Bioprod ; 16(1): 42, 2023 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-36899390

RESUMEN

BACKGROUND: Lipid formation from glycerol was previously found to be activated in Rhodotorula toruloides when the yeast was cultivated in a mixture of crude glycerol (CG) and hemicellulose hydrolysate (CGHH) compared to CG as the only carbon source. RNA samples from R. toruloides CBS14 cell cultures grown on either CG or CGHH were collected at different timepoints of cultivation, and a differential gene expression analysis was performed between cells grown at a similar physiological situation. RESULTS: We observed enhanced transcription of genes involved in oxidative phosphorylation and enzymes localized in mitochondria in CGHH compared to CG. Genes involved in protein turnover, including those encoding ribosomal proteins, translation elongation factors, and genes involved in building the proteasome also showed an enhanced transcription in CGHH compared to CG. At 10 h cultivation, another group of activated genes in CGHH was involved in ß-oxidation, handling oxidative stress and degradation of xylose and aromatic compounds. Potential bypasses of the standard GUT1 and GUT2-glycerol assimilation pathway were also expressed and upregulated in CGHH 10 h. When the additional carbon sources from HH were completely consumed, at CGHH 36 h, their transcription decreased and NAD+-dependent glycerol-3-phosphate dehydrogenase was upregulated compared to CG 60 h, generating NADH instead of NADPH with glycerol catabolism. TPI1 was upregulated in CGHH compared to cells grown on CG in all physiological situations, potentially channeling the DHAP formed through glycerol catabolism into glycolysis. The highest number of upregulated genes encoding glycolytic enzymes was found after 36 h in CGHH, when all additional carbon sources were already consumed. CONCLUSIONS: We suspect that the physiological reason for the accelerated glycerol assimilation and faster lipid production, was primarily the activation of enzymes that provide energy.

18.
Proc Natl Acad Sci U S A ; 106(22): 8888-93, 2009 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-19451643

RESUMEN

The N-end rule is a conserved degradation pathway that relates the stability of a protein to its N-terminal amino acid. Here, we present crystal structures of ClpS, the bacterial N-end rule adaptor, alone and engaged with peptides containing N-terminal phenylalanine, leucine, and tryptophan. These structures, together with a previous structure of ClpS bound to an N-terminal tyrosine, illustrate the molecular basis of recognition of the complete set of primary N-end rule amino acids. In each case, the alpha-amino group and side chain of the N-terminal residue are the major determinants of recognition. The binding pocket for the N-end residue is preformed in the free adaptor, and only small adjustments are needed to accommodate N-end rule residues having substantially different sizes and shapes. M53A ClpS is known to mediate degradation of an expanded repertoire of substrates, including those with N-terminal valine or isoleucine. A structure of Met53A ClpS engaged with an N-end rule tryptophan reveals an essentially wild-type mechanism of recognition, indicating that the Met(53) side chain directly enforces specificity by clashing with and excluding beta-branched side chains. Finally, experimental and structural data suggest mechanisms that make proteins with N-terminal methionine bind very poorly to ClpS, explaining why these high-abundance proteins are not degraded via the N-end rule pathway in the cell.


Asunto(s)
Proteínas Portadoras/metabolismo , Caulobacter crescentus/metabolismo , Proteínas Portadoras/química , Proteínas Portadoras/genética , Cristalografía por Rayos X , Endopeptidasa Clp/metabolismo , Metionina/genética , Metionina/metabolismo , Péptidos/química , Péptidos/genética , Péptidos/metabolismo , Conformación Proteica , Especificidad por Sustrato
19.
J Am Board Fam Med ; 35(3): 588-592, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35641044

RESUMEN

National telehealth policy thus far has focused on broadening access to service, specialties, and originating sites. Yet telehealth policy can further equity by providing system-level change needed to reduce structural determinants that hamper telehealth access in historically marginalized, low income, and limited English-speaking populations. The authors propose policy solutions for states and CMS to help address these structural determinants of telehealth care. A telehealth "ecosystem" grounded in the following core components would ensure equitable access to care: use of technology inclusive of economically marginalized patients, access to the technology and broadband for completing virtual visits, and concrete support for patients as they develop their digital and telehealth skills.


Asunto(s)
Pandemias , Telemedicina , Política de Salud , Humanos , Atención Primaria de Salud
20.
J Fungi (Basel) ; 8(4)2022 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-35448555

RESUMEN

The genus Rhodotorula includes basidiomycetous oleaginous yeast species. Rhodotorula babjevae can produce compounds of biotechnological interest such as lipids, carotenoids, and biosurfactants from low value substrates such as lignocellulose hydrolysate. High-quality genome assemblies are needed to develop genetic tools and to understand fungal evolution and genetics. Here, we combined short- and long-read sequencing to resolve the genomes of two R. babjevae strains, CBS 7808 (type strain) and DBVPG 8058, at chromosomal level. Both genomes are 21 Mbp in size and have a GC content of 68.2%. Allele frequency analysis indicates that both strains are tetraploid. The genomes consist of a maximum of 21 chromosomes with a size of 0.4 to 2.4 Mbp. In both assemblies, the mitochondrial genome was recovered in a single contig, that shared 97% pairwise identity. Pairwise identity between most chromosomes ranges from 82 to 87%. We also found indications for strain-specific extrachromosomal endogenous DNA. A total of 7591 and 7481 protein-coding genes were annotated in CBS 7808 and DBVPG 8058, respectively. CBS 7808 accumulated a higher number of tandem duplications than DBVPG 8058. We identified large translocation events between putative chromosomes. Genome divergence values between the two strains indicate that they may belong to different species.

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