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1.
Cell ; 187(19): 5195-5216, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39303686

RESUMEN

Microorganisms, including bacteria, archaea, viruses, fungi, and protists, are essential to life on Earth and the functioning of the biosphere. Here, we discuss the key roles of microorganisms in achieving the United Nations Sustainable Development Goals (SDGs), highlighting recent and emerging advances in microbial research and technology that can facilitate our transition toward a sustainable future. Given the central role of microorganisms in the biochemical processing of elements, synthesizing new materials, supporting human health, and facilitating life in managed and natural landscapes, microbial research and technologies are directly or indirectly relevant for achieving each of the SDGs. More importantly, the ubiquitous and global role of microbes means that they present new opportunities for synergistically accelerating progress toward multiple sustainability goals. By effectively managing microbial health, we can achieve solutions that address multiple sustainability targets ranging from climate and human health to food and energy production. Emerging international policy frameworks should reflect the vital importance of microorganisms in achieving a sustainable future.


Asunto(s)
Desarrollo Sostenible , Humanos , Naciones Unidas , Objetivos , Bacterias/metabolismo , Salud Global , Hongos/metabolismo
2.
Int J Surg Case Rep ; 123: 110277, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39305689

RESUMEN

INTRODUCTION: Corticosteroid injection (CSI) for carpal tunnel syndrome is a common diagnostic and therapeutic procedure. Adverse effects of corticosteroid injections are infrequent, though rare cases of flexor tendon rupture have been documented. PRESENTATION OF CASE: We present a case of a 67-year-old female with acute loss of left index finger flexion due to rupture of the left index flexor digitorum profundus (FDP) and the flexor digitorum superficialis (FDS) tendons and left long finger FDS tendon following numerous carpal tunnel corticosteroid injections. Intraoperatively, she was also found to have a complete rupture of the long finger FDS and partial rupture of the long finger FDP. Side-to-side tendon transfers were performed to restore the flexor tendon function. DISCUSSION: The overall incidence of serious adverse effects in patients receiving CSIs for carpal tunnel syndrome, including flexor tendon rupture, intraneural injection or gangrene, is extremely low. Only three cases of flexor tendon ruptures following CSI for carpal tunnel syndrome have been reported in the literature. Given our patient's multiple CSIs per year over the course of 6 years, she may have been at increased risk of spontaneous tendon rupture given extra-articular CSIs can result in tendon rupture as a rare, but serious complication. CONCLUSION: This case demonstrates that flexor tendon ruptures are a possible, although rare, complication following steroid injections for carpal tunnel syndrome. Proper injection techniques should be used to minimize adverse effects.

3.
Nurse Educ Today ; 143: 106379, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39236595

RESUMEN

BACKGROUND: Mindfulness has gained prominence in education as a method for enhancing student well-being and learning, yet its integration into nursing curricula remains underexplored. Student lived experiences are essential to understanding the potential benefits and challenges of mindful nursing practice. AIM: To explore the lived experiences of undergraduate nursing students who practice mindfulness as it relates to nursing education. METHODS: This was a qualitative descriptive phenomenological study. Data was collected using semi-structured Zoom interviews. Recruitment used word of mouth and snowball sampling. Out of 80 applicants, 17 undergraduate nursing students were interviewed until data saturation was achieved. Data were analyzed using Edmund Husserl's approach to descriptive phenomenology, supported by Jean Watson's Theory of Human Caring and Abraham Maslow's hierarchy of needs. RESULTS: Seven main themes emerged: Interpersonal and Transpersonal Connections, Spiritual Beliefs and Practices, Faith in the Future, Feelings of Peace, Barriers to Mindfulness in Nursing Education, Integrating Mindfulness Across the Curriculum, and Mindfulness Models in Building Professional Patterns. CONCLUSION: Data indicate nursing educators have a significant role in guiding students to mindfulness practices for the well-being of the nursing profession.

4.
PLoS Genet ; 20(8): e1011156, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39137212

RESUMEN

Phosphorus is essential in all cells' structural, metabolic and regulatory functions. For fungal cells that import inorganic phosphate (Pi) up a steep concentration gradient, surface Pi transporters are critical capacitators of growth. Fungi must deploy Pi transporters that enable optimal Pi uptake in pH and Pi concentration ranges prevalent in their environments. Single, triple and quadruple mutants were used to characterize the four Pi transporters we identified for the human fungal pathogen Candida albicans, which must adapt to alkaline conditions during invasion of the host bloodstream and deep organs. A high-affinity Pi transporter, Pho84, was most efficient across the widest pH range while another, Pho89, showed high-affinity characteristics only within one pH unit of neutral. Two low-affinity Pi transporters, Pho87 and Fgr2, were active only in acidic conditions. Only Pho84 among the Pi transporters was clearly required in previously identified Pi-related functions including Target of Rapamycin Complex 1 signaling, oxidative stress resistance and hyphal growth. We used in vitro evolution and whole genome sequencing as an unbiased forward genetic approach to probe adaptation to prolonged Pi scarcity of two quadruple mutant lineages lacking all 4 Pi transporters. Lineage-specific genomic changes corresponded to divergent success of the two lineages in fitness recovery during Pi limitation. Initial, large-scale genomic alterations like aneuploidies and loss of heterozygosity eventually resolved, as populations gained small-scale mutations. Severity of some phenotypes linked to Pi starvation, like cell wall stress hypersensitivity, decreased in parallel to evolving populations' fitness recovery in Pi scarcity, while severity of others like membrane stress responses diverged from Pi scarcity fitness. Among preliminary candidate genes for contributors to fitness recovery, those with links to TORC1 were overrepresented. Since Pi homeostasis differs substantially between fungi and humans, adaptive processes to Pi deprivation may harbor small-molecule targets that impact fungal growth, stress resistance and virulence.


Asunto(s)
Adaptación Fisiológica , Candida albicans , Proteínas Fúngicas , Fosfatos , Fosfatos/metabolismo , Candida albicans/genética , Candida albicans/metabolismo , Adaptación Fisiológica/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Concentración de Iones de Hidrógeno , Proteínas de Transporte de Fosfato/genética , Proteínas de Transporte de Fosfato/metabolismo , Mutación , Regulación Fúngica de la Expresión Génica , Humanos , Transporte Biológico/genética
5.
mBio ; : e0206324, 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39207108

RESUMEN

Host-associated microbiota form complex microbial communities that are increasingly associated with host behavior and disease. While these microbes include bacterial, archaeal, viral, and eukaryotic constituents, most studies have focused on bacteria due to their dominance in the human host and available tools for investigation. Accumulating evidence suggests microbial eukaryotes in the microbiome play pivotal roles in host health, but our understandings of these interactions are limited to a few readily identifiable taxa because of technical limitations in unbiased eukaryote exploration. Here, we combined cell sorting, optimized eukaryotic cell lysis, and shotgun sequencing to accelerate metagenomic discovery and analysis of host-associated microbial eukaryotes. Using synthetic communities with a 1% microbial eukaryote representation, the eukaryote-optimized cell lysis and DNA recovery method alone yielded a 38-fold increase in eukaryotic DNA. Automated sorting of eukaryotic cells from stool samples of healthy adults increased the number of microbial eukaryote reads in metagenomic pools by up to 28-fold compared to commercial kits. Read frequencies for identified fungi increased by 10,000× on average compared to the Human Microbiome Project and allowed for the identification of novel taxa, de novo assembly of contigs from previously unknown microbial eukaryotes, and gene prediction from recovered genomic segments. These advances pave the way for the unbiased inclusion of microbial eukaryotes in deciphering determinants of health and disease in the host-associated microbiome.IMPORTANCEMicrobial eukaryotes are common constituents of the human gut where they can contribute to local ecology and host health, but they are often overlooked in microbiome studies. The lack of attention is due to current technical limitations that are heavily biased or poorly recovered DNA from microbial eukaryotes. We developed a method to increase the representation of these eukaryotes in metagenomic sequencing of microbiome samples that allows to improve their detection compared to prior methods and allows for the identification of new species. Application of the technique to gut microbiome samples improved detection of fungi, protists, and helminths. New eukaryotic taxa and their encoded genes could be identified by sequencing a small number of samples. This approach can improve the inclusion of eukaryotes into microbiome research.

6.
Nurse Educ Pract ; 80: 104101, 2024 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-39191199

RESUMEN

AIM: To explore the experiences of undergraduate nursing students in navigating daily micro-transitions between nursing and non-nursing roles. BACKGROUND: Nursing students develop professional role identity through socialization, experience, and practice while simultaneously managing pre-existing personal roles. This dynamic creates a training ground for future sustainable practice. DESIGN: Qualitative, cross-sectional, interpretive phenomenological design with hermeneutics. METHODS: Seventeen undergraduate nursing students participated online in semi-structured, audiovisual-recorded interviews until data saturation was reached. RESULTS: Three main themes emerged: 1) Strategies for Getting In and Out of Nurse Mode, 2) Cultivating Mindful Nursing Practice, and 3) Nursing Student Socialization and Immersion. Findings indicated that nursing students noticed benefits in their personal and professional lives as they developed this skill. Findings also suggested that students need support from their educators to ensure they are not trapped in nurse mode while learning to navigate nurse role identity. CONCLUSIONS: Understanding and supporting nursing students in managing role micro-transitions are crucial. Findings indicated a functional need for nursing students to understand and apply knowledge and skills regarding a) when to initiate a role micro-transition and b) how to complete a micro-transition effectively between a nursing and non-nursing role. Educational strategies and support systems addressing this need may improve future nursing professionals' quality of life and clinical practice.

7.
Cells ; 13(15)2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39120315

RESUMEN

Nuclear hormone receptors (NHRs) are a family of ligand-regulated transcription factors that control key aspects of development and physiology. The regulation of NHRs by ligands derived from metabolism or diet makes them excellent pharmacological targets, and the mechanistic understanding of how NHRs interact with their ligands to regulate downstream gene networks, along with the identification of ligands for orphan NHRs, could enable innovative approaches for cellular engineering, disease modeling and regenerative medicine. We review recent discoveries in the identification of physiologic ligands for NHRs. We propose new models of ligand-receptor co-evolution, the emergence of hormonal function and models of regulation of NHR specificity and activity via one-ligand and two-ligand models as well as feedback loops. Lastly, we discuss limitations on the processes for the identification of physiologic NHR ligands and emerging new methodologies that could be used to identify the natural ligands for the remaining 17 orphan NHRs in the human genome.


Asunto(s)
Metaboloma , Receptores Citoplasmáticos y Nucleares , Humanos , Receptores Citoplasmáticos y Nucleares/metabolismo , Ligandos , Animales
8.
Int J Mol Sci ; 25(14)2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39063154

RESUMEN

Quantitative assessment of nucleophosmin 1 (NPM1) mutation status is integral to evaluating measurable residual disease (MRD) in NPM1-mutated acute myeloid leukemia (AML) patients. In a retrospective study, leftover peripheral blood (PB) specimens (n = 40) which were collected for routine clinical diagnostic evaluations of AML disease burden were tested by both a novel automated RT-qPCR quantitative NPM1 assay (Xpert NPM1 mutation assay) and the NPM1 mutA, mutB&D MutaQuant kit. Based on a Deming regression analysis, there was a high correlation (slope = 0.92; intercept = 0.12; Pearson's r = 0.982) between the quantitative results of the Xpert NPM1 mutation assay and the NPM1 mutA, mutB&D MutaQuant kit. The Xpert test quantitative results are thus highly correlated with the comparator method and the former has potential as a useful alternative for the monitoring of AML patients with a known NPM1 mutation.


Asunto(s)
Leucemia Mieloide Aguda , Mutación , Proteínas Nucleares , Nucleofosmina , Reacción en Cadena en Tiempo Real de la Polimerasa , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/diagnóstico , Proteínas Nucleares/genética , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Estudios Retrospectivos , Neoplasia Residual/genética , Neoplasia Residual/diagnóstico , Masculino , Femenino , Persona de Mediana Edad
9.
mSphere ; 9(8): e0064123, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39012122

RESUMEN

Fungi were some of the earliest organismal systems used to explore mutational processes and its phenotypic consequences on members of a species. Yeasts that cause significant human disease were quickly incorporated into these investigations to define the genetic and phenotypic drivers of virulence. Among Candida species, Candida albicans has emerged as a model for studying genomic processes of evolution because of its clinical relevance, relatively small genome, and ability to tolerate complex chromosomal changes. Here, we describe major recent findings that used evolution of strains from defined genetic backgrounds to delineate mutational and adaptative processes and include how nascent exploration into naturally occurring variation is contributing to these conceptual frameworks. Ultimately, efforts to discern adaptive mechanisms used by C. albicans will continue to divulge new biology and can better inform treatment regimens for the increasing prevalence of fungal disease.


Asunto(s)
Candida albicans , Variación Genética , Candida albicans/genética , Candida albicans/patogenicidad , Candida albicans/clasificación , Humanos , Evolución Molecular , Genoma Fúngico , Virulencia/genética , Candidiasis/microbiología , Evolución Biológica
10.
Artículo en Inglés | MEDLINE | ID: mdl-38850239

RESUMEN

Green fluorescent protein has long been a favorite protein for demonstrating protein purification in the biochemistry lab course. The protein's vivid green color helps demonstrate to students the concept(s) behind affinity or ion exchange chromatography. We designed a series of introduction to biochemistry labs utilizing a thermostable green protein (TGP-E) engineered to have unusually high thermostability. This protein allows students to proceed through purification and characterization without the need to keep protein samples on ice. The 5-week lab series begins with an introduction to molecular biology techniques during weeks 1 and 2, where site-directed mutagenesis is used introduce, a single nucleotide change that shifts the fluorescent spectra of TGP-E to either cyan (CTP-E) or yellow (YTP-E). Students identify successful mutagenesis reaction by the color of a small expression sample after induction with IPTG. Next, students purify either the TGP-E (control-typically one group volunteers), YTP-E, or CTP-E protein as a 1-week lab. During the following week's lab, students run SDS-PAGE to verify protein purity, bicinchoninic acid assay to quantify protein yield, and absorbance and fluorescence spectra to characterize their protein's fluorescent character. The final lab in the series investigates the thermostability of YTP-E and CTP-E compared with TGP-E using a fluorescence plate reader. This 5-week series of experiments provide students with experience in several key biochemistry techniques and allows the students to compare properties of mutations. At the end of the course, the students will write a research report and give a short presentation over their results.

11.
J Allied Health ; 53(2): 136-141, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38834340

RESUMEN

With growing recognition that climate change is a significant threat to human health, allied health professionals are increasingly recognized as critical allies in addressing this threat. This article describes the approach that Rush University's College of Sciences is pursuing to better prepare health sciences students for this reality. Faculty and students enrolled across all programs of the College were surveyed regarding their levels of concern about global warming using items from the Six Americas Survey, as well as perceived importance of planetary health curricular elements adapted from the Planetary Health Report Card. Faculty were additionally asked about perceived opportunities to bring planetary health education into each of the degree programs offered by the university. A total of 37 faculty and 43 students completed the survey, collectively representing all programs in the college. Responses reflected widespread interest in expanding planetary health education, but topic priorities and optimal methods for implementation differed between programs. Although the survey process had limitations, it demonstrated the need for greater attention to planetary health across curricula and offered more efficient approaches implementing this essential content across programs.


Asunto(s)
Curriculum , Humanos , Cambio Climático , Evaluación de Necesidades , Docentes , Femenino , Masculino
12.
Kidney Blood Press Res ; 49(1): 495-512, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38824925

RESUMEN

INTRODUCTION: Opioid analgesics are often used to manage moderate to severe pain. A significant proportion of patients taking opioids have compromised kidney function. This systematic review aimed to examine the available evidence on the safety and analgesic effect of opioid use in adults with kidney disease. METHODS: We searched eight electronic databases from inception to January 26, 2023. Published original research articles in English reporting on opioid use and pharmacokinetic data among adults with reduced renal function were included. Article screening, data extraction, and quality assessment were conducted by at least two investigators independently. This review was registered prospectively on PROSPERO (ID: CRD42020159091). RESULTS: There were 32 observational studies included, 14 of which reported on morphine use, three involved fentanyl use, two involved hydromorphone use, and 13 articles reported on other opioids including codeine, dihydrocodeine, and buprenorphine. CONCLUSION: There is limited and low-quality evidence to inform the safety and analgesic effect of opioid use in reduced renal function. Morphine remains the opioid for which there is the most evidence available on safety and analgesic effect in the context of renal disease. Greater caution and consideration of potential risks and benefits should be applied when using other opioids. Further high-quality studies examining clinical outcomes associated with the use of different opioids and opioid doses in renal disease are warranted.


Asunto(s)
Analgésicos Opioides , Enfermedades Renales , Humanos , Analgésicos Opioides/uso terapéutico , Analgésicos Opioides/efectos adversos , Morfina/uso terapéutico , Morfina/efectos adversos , Dolor/tratamiento farmacológico
14.
Neurosurg Clin N Am ; 35(3): 287-291, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38782521

RESUMEN

Idiopathic intracranial hypertension is defined by headaches and a decline in visual acuity due to increased intracranial pressure. Treatment options historically included weight loss, acetazolamide, and/or cerebrospinal fluid diversion surgery. Recent understanding of the contributions of dural venous sinus hypertension and stenosis has led to venous sinus stenting as a treatment option.


Asunto(s)
Seudotumor Cerebral , Humanos , Acetazolamida/uso terapéutico , Senos Craneales/cirugía , Hipertensión Intracraneal/terapia , Seudotumor Cerebral/cirugía , Seudotumor Cerebral/terapia , Stents
15.
J Neurosurg Case Lessons ; 7(19)2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38710112

RESUMEN

BACKGROUND: Unilateral cranial nerve (CN) VI, or abducens nerve, palsy is rare in children and has not been reported in association with Chiari malformation type 1 (CM1) in the absence of other classic CM1 symptoms. OBSERVATIONS: A 3-year-old male presented with acute incomitant esotropia consistent with a unilateral, left CN VI palsy and no additional neurological symptoms. Imaging demonstrated CM1 without hydrocephalus or papilledema, as well as an anterior inferior cerebellar artery (AICA) vessel loop in the immediate vicinity of the left abducens nerve. Given the high risk of a skull base approach for direct microvascular decompression of the abducens nerve and the absence of other classic Chiari symptoms, the patient was initially observed. However, as his palsy progressed, he underwent posterior fossa decompression with duraplasty (PFDD), with the aim of restoring global cerebrospinal fluid dynamics and decreasing possible AICA compression of the left abducens nerve. Postoperatively, his symptoms completely resolved. LESSONS: In this first reported case of CM1 presenting as a unilateral abducens palsy in a young child, possibly caused by neurovascular compression, the patient's symptoms resolved after indirect surgical decompression via PFDD.

16.
Orthop J Sports Med ; 12(5): 23259671241246061, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38774386

RESUMEN

Background: Significant psychological impact and prevalence of posttraumatic stress disorder (PTSD) have been well documented in patients sustaining anterior cruciate ligament injury. Purpose: To examine PTSD symptomatology in baseball players after sustaining elbow ulnar collateral ligament (UCL) injury. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Male baseball players of various competition levels (high school through Minor League Baseball [MiLB]) who underwent surgery for a UCL injury between April 2019 and June 2022 participated in the study. Before surgery, patients completed the Impact of Event Scale-Revised (IES-R) to assess PTSD symptomatology. Subgroup analysis was conducted according to level of play and player position. Results: A total of 104 male baseball players with a mean age of 19.4 years (range, 15-29 years) were included in the study; 32 players (30.8%) were in high school, 65 (62.5%) were in college, and 7 (6.7%) were in MiLB. There were 64 (61.5%) pitchers, 18 (17.3%) position players, and 22 (21.2%) 2-way players (both pitching and playing on the field). A total of 30 (28.8%) patients scored high enough on the IES-R to support PTSD as a probable diagnosis, and another 22 patients (21.2%) scored high enough to support PTSD as a clinical concern. Nineteen patients (18.3%) had potentially severe PTSD. Only 4 players (3.8%) were completely asymptomatic. Subgroup analysis revealed college players as significantly more symptomatic than high school players (P = .02), and 2-way players were found to be significantly less susceptible to developing symptoms of PTSD compared with pitchers (P = .04). Conclusion: Nearly 30% of baseball players who sustained a UCL injury qualified for a probable diagnosis of PTSD based on the IES-R. Pitchers and college athletes were at increased risk for PTSD after UCL injury compared with 2-way players and high school athletes, respectively.

17.
Am J Emerg Med ; 81: 159.e7-159.e10, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38658200

RESUMEN

INTRODUCTION: Non-traumatic headache is a common complaint seen in the emergency department (ED), accounting for 2.3% of ED visits per year in the United States (Munoz-Ceron et al., 2019). When approaching the workup and management of headache, an emergency medicine physician is tasked with generating a deadly differential by means of a thorough history and physical exam to determine the next best steps. CASE: A 21-year-old male presented to the emergency department with a debilitating new-onset headache, preceded by an isolated vertiginous event 3 days prior. He was found to have a normal neurologic examination. A non-contrast CT scan of the head revealed a large hypodensity within the left cerebellum with a subsequent MRA of the brain and neck notable for a left vertebral artery dissection, complicated by an ischemic cerebellar stroke. DISCUSSION: With an estimated incidence of 1-5 per 100,000, vertebral artery dissection is a rare cause of stroke within the general population and carries with it a high degree of morbidity and mortality (Rodallec et al., 2008). Vertebral artery dissection is a result of blood penetrating the intimal wall of the artery to form an intramural hematoma. Diagnosis can be difficult in cases presenting subacutely but a thorough history evaluating for red flags and using simple but highly sensitive exams such as the bedside HINTS exam can increase pretest probability of stroke. Clinical syndromes, red flags, and time from onset of symptoms should guide imaging modalities such as CT, CTA, MRI, and MRA in detection of small ischemic changes, intimal flaps, and luminal thromboses. CONCLUSION: Vertebral artery dissection should remain high on the differential for an emergency medicine physician when history is suggestive of a new onset headache, preceded by vertiginous symptoms. An absence of recent trauma and a normal neurologic examination does not eliminate the diagnosis.


Asunto(s)
Cefalea , Disección de la Arteria Vertebral , Humanos , Disección de la Arteria Vertebral/complicaciones , Disección de la Arteria Vertebral/diagnóstico , Disección de la Arteria Vertebral/diagnóstico por imagen , Masculino , Adulto Joven , Cefalea/etiología , Tomografía Computarizada por Rayos X , Servicio de Urgencia en Hospital , Angiografía por Resonancia Magnética , Diagnóstico Diferencial
18.
Cell Commun Signal ; 22(1): 221, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38594674

RESUMEN

VEGFR2 (Vascular endothelial growth factor receptor 2) is a central regulator of placental angiogenesis. The study of the VEGFR2 proteome of chorionic villi at term revealed its partners MDMX (Double minute 4 protein) and PICALM (Phosphatidylinositol-binding clathrin assembly protein). Subsequently, the oxytocin receptor (OT-R) and vasopressin V1aR receptor were detected in MDMX and PICALM immunoprecipitations. Immunogold electron microscopy showed VEGFR2 on endothelial cell (EC) nuclei, mitochondria, and Hofbauer cells (HC), tissue-resident macrophages of the placenta. MDMX, PICALM, and V1aR were located on EC plasma membranes, nuclei, and HC nuclei. Unexpectedly, PICALM and OT-R were detected on EC projections into the fetal lumen and OT-R on 20-150 nm clusters therein, prompting the hypothesis that placental exosomes transport OT-R to the fetus and across the blood-brain barrier. Insights on gestational complications were gained by univariable and multivariable regression analyses associating preeclampsia with lower MDMX protein levels in membrane extracts of chorionic villi, and lower MDMX, PICALM, OT-R, and V1aR with spontaneous vaginal deliveries compared to cesarean deliveries before the onset of labor. We found select associations between higher MDMX, PICALM, OT-R protein levels and either gravidity, diabetes, BMI, maternal age, or neonatal weight, and correlations only between PICALM-OT-R (p < 2.7 × 10-8), PICALM-V1aR (p < 0.006), and OT-R-V1aR (p < 0.001). These results offer for exploration new partnerships in metabolic networks, tissue-resident immunity, and labor, notably for HC that predominantly express MDMX.


Asunto(s)
Diabetes Mellitus , Preeclampsia , Femenino , Humanos , Recién Nacido , Embarazo , Número de Embarazos , Oxitocina/metabolismo , Placenta/metabolismo , Preeclampsia/metabolismo , Proteómica , Receptores de Oxitocina/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo
19.
Microbiology (Reading) ; 170(3)2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38446018

RESUMEN

The genetic background between strains of a single species and within a single strain lineage can significantly impact the expression of biological traits. This genetic variation may also reshape epigenetic mechanisms of cell identity and environmental responses that are controlled by interconnected transcriptional networks and chromatin-modifying enzymes. Histone deacetylases, including sirtuins, are critical regulators of chromatin state and have been directly implicated in governing the phenotypic transition between the 'sterile' white state and the mating-competent opaque state in Candida albicans, a common fungal commensal and pathogen of humans. Here, we found that a previously ambiguous role for the sirtuin SIR2 in C. albicans phenotypic switching is likely linked to the genetic background of mutant strains produced in the RM lineage of SC5314. SIR2 mutants in a specific lineage of BWP17 displayed increased frequencies of switching to the opaque state compared to the wild-type. Loss of SIR2 in other SC5314-derived backgrounds, including newly constructed BWP17 sir2Δ/Δ mutants, failed to recapitulate the increased white-opaque switching frequencies observed in the original BWP17 sir2Δ/Δ mutant background. Whole-genome sequencing revealed the presence of multiple imbalanced chromosomes and large loss of heterozygosity tracts that likely interact with SIR2 to increase phenotypic switching in this BWP17 sir2Δ/Δ mutant lineage. These genomic changes are not found in other SC5314-derived sir2Δ/Δ mutants that do not display increased opaque cell formation. Thus, complex karyotypes can emerge during strain construction that modify mutant phenotypes and highlight the importance of validating strain background when interpreting phenotypes.


Asunto(s)
Candida albicans , Cromatina , Humanos , Candida albicans/genética , Epigénesis Genética , Redes Reguladoras de Genes , Fenotipo
20.
World Neurosurg ; 185: e1169-e1176, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38503403

RESUMEN

OBJECTIVE: The aim of this study is to gauge the current social climate in neurosurgical residency training and attitudes regarding sexual orientation and gender identity. METHODS: We conducted a cross-sectional study through a 35-question questionnaire distributed to roughly 1700 residents at all U.S. neurosurgical residency programs. RESULTS: A total of 107 responses were obtained. Seventeen residents (16%) identified as being an LGBTQ+ individual. The majority (76%) of LGBTQ+ residents were concerned about how their sexual orientation would be perceived while applying to programs, and 47% endorsed purposefully concealing sexual orientation at work for fear of rejection or reprisal. More than half (56%) of those surveyed have witnessed homophobic/transphobic remarks by patients. While at work, 29% of LGBTQ+ individuals stated they are uncomfortable being open with their sexual orientation, and 3 LGBTQ+ individuals admitted being the target of direct homophobic/transphobic comments. CONCLUSIONS: This is the first study to our knowledge that has been conducted assessing the presence, perception, and treatment of LGBTQ+ trainees in neurosurgical residency. Our study outlines the challenges LGBTQ+ individuals face when applying to neurosurgical programs, which involves the perception of their sexual orientation, their witnessed instances of homophobic and transphobic comments by coworkers and patients, and their hesitation with discussing their social lives compared with their non-LGBTQ+ peers at work for fear of judgment or reprisal. Ongoing research is needed to address these issues to obtain workplace respect and fairness in this population and thus create an accepting atmosphere and achieve social justice in neurosurgery training.


Asunto(s)
Internado y Residencia , Neurocirugia , Minorías Sexuales y de Género , Humanos , Minorías Sexuales y de Género/psicología , Masculino , Femenino , Estados Unidos , Estudios Transversales , Neurocirugia/educación , Encuestas y Cuestionarios , Adulto , Actitud del Personal de Salud , Conducta Sexual/psicología
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