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1.
Front Psychiatry ; 15: 1377174, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39234619

RESUMO

Introduction: Qualitative research methods can be used to obtain a deeper understanding of patient experience by collecting information in the patients' own words about their encounters, perspectives, and feelings. In this study, patients with schizophrenia were interviewed to capture their voice and to complement the quantitative data typically obtained in clinical trials. Methods: Semi-structured exit interviews were conducted with 41 patients who completed or prematurely discontinued from a phase 3, open-label trial (NCT02873208). The interview guide included open-ended questions on current and prior disease burden, symptoms, quality of life, and treatment experiences. Steps taken to reduce interview stress and secure the validity of data included interviewer sensitivity training specific to mental health conditions and schizophrenia, use of in-person interviews whenever possible and use of videoconferencing for remote interviews to promote trust and comfort, and working closely with clinical site staff to identify patient eligibility and willingness to participate. Transcripts based on audio recordings were content coded and analyzed using thematic analysis; a post-hoc quantitative content analysis was conducted. Results: Patients reported that the symptoms of schizophrenia negatively impacted their work, relationships, self-esteem, emotional health, and daily activities. Most patients had positive experiences with medications that alleviated hallucinations, depression, and anxiety. However, side effects of medications were associated with negative impacts on physical, emotional, behavioral, and cognitive health. Lack of energy/drowsiness, weight gain, mood changes, and involuntary movements were the most common side effects reported with the use of antipsychotic medications. Patients reported unmet treatment needs related to better symptom control and to improved social and physical functioning. Conclusion: Collection of qualitative information within a schizophrenia clinical development process provides value and insights into patients' views on burden of illness, experiences with previous medications, and experiences following participation in a clinical trial and can inform design for future studies.

2.
Work ; 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39240613

RESUMO

BACKGROUND: In most Western countries, senior workers have increased their participation in the workforce. However, at the same time, early retirement also increases. The reasons behind this early exit from the workforce are still unclear. OBJECTIVE: This qualitative study aims to explore the antecedents of and experiences with a voluntary exit from working life before the expected retirement age of 65 in Sweden. METHODS: Data consist of semi-structured interviews with 18 participants who exited working life between the ages of 61-63. In Sweden, these ages are considered as an early exit from working life since, for many years, the expected retirement age has been 65. Qualitative content analysis with an abductive approach was utilized. RESULTS: The analysis revealed four sub-themes: 1) Health benefits with an early exit from working life (with the categories: own health status, the possibility for recovery time, and avoidance of strain); 2) Having economic conditions that enable an early exit from working life (with the categories: offers from the employer and financial compromises); 3) Social benefits with an early exit from working life (with the categories: enabling more time with my social network and avoidance of unsatisfying social work environment); 4) Self-fulfillment activities during the senior years (with the categories: enabling time for activities beyond work and avoidance of decreased job satisfaction. CONCLUSION: This variety of antecedents of and experiences with a voluntary early exit from working life before the expected retirement age highlights that the ongoing increased statutory retirement age also increases the risk for extended inequalities among the aging population.

3.
Int J Mol Sci ; 25(17)2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39273443

RESUMO

Vascular smooth muscle cells (SMCs) can transition between a quiescent contractile or "differentiated" phenotype and a "proliferative-dedifferentiated" phenotype in response to environmental cues, similar to what in occurs in the wound healing process observed in fibroblasts. When dysregulated, these processes contribute to the development of various lung and cardiovascular diseases such as Chronic Obstructive Pulmonary Disease (COPD). Long non-coding RNAs (lncRNAs) have emerged as key modulators of SMC differentiation and phenotypic changes. In this study, we examined the expression of lncRNAs in primary human pulmonary artery SMCs (hPASMCs) during cell-to-cell contact-induced SMC differentiation. We discovered a novel lncRNA, which we named Differentiation And Growth Arrest-Related lncRNA (DAGAR) that was significantly upregulated in the quiescent phenotype with respect to proliferative SMCs and in cell-cycle-arrested MRC5 lung fibroblasts. We demonstrated that DAGAR expression is essential for SMC quiescence and its knockdown hinders SMC differentiation. The treatment of quiescent SMCs with the pro-inflammatory cytokine Tumor Necrosis Factor (TNF), a known inducer of SMC dedifferentiation and proliferation, elicited DAGAR downregulation. Consistent with this, we observed diminished DAGAR expression in pulmonary arteries from COPD patients compared to non-smoker controls. Through pulldown experiments followed by mass spectrometry analysis, we identified several proteins that interact with DAGAR that are related to cell differentiation, the cell cycle, cytoskeleton organization, iron metabolism, and the N-6-Methyladenosine (m6A) machinery. In conclusion, our findings highlight DAGAR as a novel lncRNA that plays a crucial role in the regulation of cell proliferation and SMC differentiation. This paper underscores the potential significance of DAGAR in SMC and fibroblast physiology in health and disease.


Assuntos
Diferenciação Celular , Proliferação de Células , Fibroblastos , Miócitos de Músculo Liso , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fibroblastos/metabolismo , Diferenciação Celular/genética , Miócitos de Músculo Liso/metabolismo , Proliferação de Células/genética , Artéria Pulmonar/metabolismo , Artéria Pulmonar/citologia , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/citologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/patologia , Células Cultivadas
4.
Artigo em Inglês | MEDLINE | ID: mdl-39266886

RESUMO

Educational escape rooms within health sciences education are gaining traction as a unique and engaging game-based strategy for reviewing instructional content. Educational escape rooms cultivate valuable skills such as teamwork, communication, creativity, attention to detail, and the ability to apply knowledge under time pressures. While several studies have independently assessed learners' knowledge gains after educational escape room interventions, the present work meta-analyzes the efficacy of educational escape rooms across studies and student learners within health sciences education. A systematic search across seven databases was performed by a health sciences librarian from inception to March 24, 2023. Record screenings, full-text reviews, and data extractions were managed within Covidence. MERSQI criteria were used to assess study quality. Pooled effect sizes (Standardized Mean Differences = SMD) were estimated through meta-analysis to summarize learner performance outcomes after educational escape room interventions. Eleven studies followed a longitudinal pretest-posttest design, and five studies followed a control-treatment group design. Learners' posttest scores after participating in an educational escape room were statistically higher than their pretest scores as indicated by a large positive summary effect size (SMD ≥ 0.893; p <0.001). Educational escape rooms were also effective for treatment group participants (n = 508), who significantly outperformed (SMD = 0.616; p <0.001) control group participants (n = 555). Most escape rooms were employed as a mechanism for reviewing educational content. This meta-analytic review suggests escape rooms are effective educational interventions for increasing knowledge gains among health sciences learners and highlights common implementation practices to help guide educators interested in this game-based learning approach.

5.
J Health Organ Manag ; ahead-of-print(ahead-of-print)2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39327726

RESUMO

PURPOSE: The aim of the study was to compare the explanatory power of the dissatisfaction-based account of aged care employee turnover against that of Lee and Mitchell's (1994) unfolding theory of turnover. DESIGN/METHODOLOGY/APPROACH: Mixed method prospective cohort study with three waves of employee survey data and an exit interview drawn from employees of a large Australian not-for-profit aged care provider. Independent t tests and mediated logistic regression analyses were conducted. Final sample: nStayers at Wave 3 = 138; nLeavers by Wave 3 = 42). FINDINGS: The classic dissatisfaction-based theory accounts for 19% of actual leavers. The five unfolding theory exit pathways accounted for 73.8% of all leavers. Stayers had the same dissatisfaction as leavers. Shock-based turnover (40.5% of all leavers) was more common than dissatisfaction-based turnover (33.5%). An additional 11.9% of leavers resigned to retire from paid work. RESEARCH LIMITATIONS/IMPLICATIONS: Dissatisfaction-based theory provided a relatively weak explanation of aged care turnover in this organisation. The unfolding theory provided a better and more nuanced account of employee leaving. PRACTICAL IMPLICATIONS: Unfolding theory exit interviews will assist aged care employers to better identify organizationally specific exit patterns and assist in finding appropriate organizational solutions to employee turnover. ORIGINALITY/VALUE: This paper provides the first direct comparison of two explanations of aged care employee turnover and provides guidance to better retention at a time of labour shortage.


Assuntos
Satisfação no Emprego , Reorganização de Recursos Humanos , Humanos , Estudos Prospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Austrália , Entrevistas como Assunto , Inquéritos e Questionários
6.
mBio ; : e0238024, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39345210

RESUMO

Toxoplasma gondii possesses a highly polarized secretory pathway that contains both broadly conserved eukaryotic organelles and unique apicomplexan organelles, which play essential roles in the parasite's lytic cycle. As in other eukaryotes, the T. gondii Golgi apparatus sorts and modifies proteins prior to their distribution to downstream organelles. Many of the typical trafficking factors found involved in these processes are missing from apicomplexan genomes, suggesting that these parasites have evolved unique proteins to fill these roles. Here, we identify a Golgi-localizing protein (ULP1), which is structurally similar to the eukaryotic trafficking factor p115/Uso1. We demonstrate that depletion of ULP1 leads to a dramatic reduction in parasite fitness that is the result of defects in microneme secretion, invasion, replication, and egress. Using ULP1 as bait for TurboID proximity labeling and immunoprecipitation, we identify 11 more Golgi-associated proteins and demonstrate that ULP1 interacts with the T. gondii-conserved oligomeric Golgi (COG) complex. These proteins include both conserved trafficking factors and parasite-specific proteins. Using a conditional knockdown approach, we assess the effect of each of these 11 proteins on parasite fitness. Together, this work reveals a diverse set of T. gondii Golgi-associated proteins that play distinct roles in the secretory pathway. As several of these proteins are absent outside of the Apicomplexa, they represent potential targets for the development of novel therapeutics against these parasites. IMPORTANCE: Apicomplexan parasites such as Toxoplasma gondii infect a large percentage of the world's population and cause substantial human disease. These widespread pathogens use specialized secretory organelles to infect their host cells, modulate host cell functions, and cause disease. While the functions of the secretory organelles are now better understood, the Golgi apparatus of the parasite remains largely unexplored, particularly regarding parasite-specific innovations that may help direct traffic intracellularly. In this work, we characterize ULP1, a protein that is unique to parasites but shares structural similarity to the eukaryotic trafficking factor p115/Uso1. We show that ULP1 plays an important role in parasite fitness and demonstrate that it interacts with the conserved oligomeric Golgi (COG) complex. We then use ULP1 proximity labeling to identify 11 additional Golgi-associated proteins, which we functionally analyze via conditional knockdown. This work expands our knowledge of the Toxoplasma Golgi apparatus and identifies potential targets for therapeutic intervention.

7.
BMC Health Serv Res ; 24(1): 1111, 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39317932

RESUMO

BACKGROUND: Worldwide growing shortages among health care staff are observed. This also holds true for medical assistants in Germany. Medical assistants mainly work in outpatient care and are the first point of contact for patients while performing clinical and administrative tasks. We sought to explore profession turnover among medical assistants, that is, in terms of the underlying decision-making process, the reasons for leaving the medical assistant profession and potential retention measures from the perspective of former medical assistants. METHODS: For this qualitative study, we conducted semi-structured telephone interviews with 20 former medical assistants between August and November 2023. Eligible for participation were medical assistants who (i) were of legal age, (ii) completed medical assistant vocational training and ii) were formerly employed as a medical assistant, but currently employed in another profession. The interviews were recorded, transcribed verbatim and content-analyzed. RESULTS: Former medical assistants expressed various, often interrelated reasons for leaving the profession. These were changes in priorities throughout their career (e.g., in terms of working hours and salary), a constant high workload, barriers to further training, poor career prospects, and poor interpersonal relationships particularly with supervisors, but also within the team and with patients as well as the perception of insufficient recognition by politics and society. Suggestions of former medical assistants to motivate medical assistants to stay in their profession included amongst others higher salaries, more flexible work structures, improved career prospects, and more recognition from supervisors, patients, and society. CONCLUSION: Our study provides insights into the complex decision-making process underlying ultimate medical assistant profession turnover. In light of an already existing shortage of medical assistants, we suggest to further explore how the suggested interventions that aim at retention of working medical assistants can be implemented.


Assuntos
Reorganização de Recursos Humanos , Pesquisa Qualitativa , Humanos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Alemanha , Reorganização de Recursos Humanos/estatística & dados numéricos , Entrevistas como Assunto , Satisfação no Emprego , Carga de Trabalho , Salários e Benefícios , Assistentes Médicos
8.
Cureus ; 16(8): e67188, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39295654

RESUMO

In forensic examinations, gunshot injury cases can sometimes present unusual challenges. Typically, a gunshot injury involves an entry wound where the bullet penetrates the body and an exit wound where the bullet exits. If the bullet does not exit the body, it can often be recovered from the body cavity. However, there are instances where the entry wound is identified, but both the exit wound and the bullet appear to be missing. This paper explores such a paradox, where, despite a thorough postmortem examination, neither the bullet nor the exit wound is found. We consider various possibilities and analyze whether this was indeed a gunshot injury. Could the bullet still be inside the body, or might it have taken an unexpected route? This paper aims to clarify this puzzling phenomenon through detailed analysis and underscore the importance of meticulous forensic investigation in complex cases.

9.
Heliyon ; 10(17): e35291, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39296186

RESUMO

Expressway exit areas experience traffic diversion and complex road conditions, making them accident-prone areas. In this study, transverse and fishbone visual illusion deceleration markings were selected to optimize the induction facilities at expressway exits. The research aims to investigate the impact of these markings on the driving behavior, cognitive load, and physiological characteristics of drivers in various distracted scenarios at expressway exit areas. Furthermore, a comprehensive evaluation of each experimental scheme is conducted using the Matter-Element Extension Model. The study found that the implementation of deceleration markings can effectively enhance driver alertness and lane change awareness, enabling drivers to reduce their speed to near the speed limit in exit areas without compromising driving comfort. Compared to the situation without markings, drivers begin to decelerate approximately 600 m earlier and exit the ramp when markings are present. Fishbone deceleration markings, in contrast to transverse markings, result in lower vehicle speeds, smoother deceleration, and more effectively stimulate drivers' intention to change lanes, guiding them to make the final lane change earlier. Based on the comprehensive evaluation results, it is recommended that transverse or fishbone deceleration markings be considered in engineering practice. These markings have not produced significant effects on driver visual fatigue and driving load, with fishbone markings demonstrating superior comprehensive evaluation outcomes. These research findings can provide valuable insights for future expressway exit area marking design schemes, further enhancing driver safety.

10.
Cell Rep ; 43(9): 114656, 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39240714

RESUMO

Cohesin is key to eukaryotic genome organization and acts throughout the cell cycle in an ATP-dependent manner. The mechanisms underlying cohesin ATPase activity are poorly understood. Here, we characterize distinct steps of the human cohesin ATPase cycle and show that the SMC1A and SMC3 ATPase domains undergo specific but concerted structural rearrangements along this cycle. Specifically, whereas the proximal coiled coil of the SMC1A ATPase domain remains conformationally stable, that of the SMC3 displays an intrinsic flexibility. The ATP-dependent formation of the heterodimeric SMC1A/SMC3 ATPase module (engaged state) favors this flexibility, which is counteracted by NIPBL and DNA binding (clamped state). Opening of the SMC3/RAD21 interface (open-engaged state) stiffens the SMC3 proximal coiled coil, thus constricting together with that of SMC1A the ATPase module DNA-binding chamber. The plasticity of the ATP-dependent interface between the SMC1A and SMC3 ATPase domains enables these structural rearrangements while keeping the ATP gate shut. VIDEO ABSTRACT.


Assuntos
Adenosina Trifosfatases , Proteínas de Ciclo Celular , Proteínas Cromossômicas não Histona , Coesinas , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/química , Proteínas de Ciclo Celular/genética , Proteínas Cromossômicas não Histona/metabolismo , Proteínas Cromossômicas não Histona/química , Humanos , Adenosina Trifosfatases/metabolismo , Adenosina Trifosfatases/química , Domínios Proteicos , Trifosfato de Adenosina/metabolismo , Ligação Proteica , Proteoglicanas de Sulfatos de Condroitina
11.
Kidney Int Rep ; 9(9): 2739-2749, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39291192

RESUMO

Introduction: Exit-site infections (ESI) of central venous catheters for hemodialysis (CVC-HD) has been associated with early catheter removal and an increased risk of CVC-HD related bacteremia. No specific clinical scales to predict ESI have previously been validated. Methods: A multicenter prospective cohort study was performed to validate the proposed scale, which is based on the following 5 signs and symptoms: (i) pain at exit site during interdialytic period; (ii) hyperemia or erythema ≥2 cm from exit site; (iii) inflammation, induration, or swelling at exit site; (iv) fever ≥38 °C not attributable to other causes, and (v) obvious abscess or purulent exudate at the exit site. Adult patients with a tunneled CVC-HD for at least 1 month after insertion has been included. During each hemodialysis session, the exit site was assessed with the proposed scale by nurses. If any item was present, a pericatheter skin swab culture was collected: positive results were gold standard. The scale was validated using receiver operating characteristic (ROC) curves and logistic regression analysis. For this purpose, the logit function was applied, and the ESI probability calculated, as elogit ESI/1 + elogit ESI. Results: Three hundred thirty-seven CVC-HDs from 310 patients were analyzed, producing 515 cultures (117 infected and 398 healthy). The final version of the scale includes the following 3 signs and symptoms, which present the greatest predictive capacity: (i) pain at exit site during interdialytic period, (ii) hyperemia or erythema ≥2 cm from exit site, and (iii) abscess or purulent exudate at the exit site. The final version generated an area under the ROC curve (AUC) of 88.3% (95% confidence interval [CI]: 85.2%-91%; P < 0.001), Youden index 0.7557 ≈ 1, sensitivity 80.34% (95% CI: 71.36%-87.71%) and specificity 95.23% (95% CI: 92.73%-97%). Conclusions: The validation shows that the scale has good predictive properties, detecting approximately 90% of ESI with very acceptable validity parameters.

12.
Brain Stimul ; 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39321914

RESUMO

BACKGROUND: As clinical trials involving implantable neural devices (INDs) increase in frequency and attract greater public attention, it is paramount to ensure they are conducted in alignment with fundamental ethical guidelines. Particular focus must be placed on the often underexplored aspect of trial termination for INDs. OBJECTIVE: To systematically review the ethical challenges encountered in clinical trials for INDs at the juncture of trial termination. METHODS: We conducted a rapid review using PubMed with two specific search queries, including all publications addressing ethical issues in the context of IND clinical trials. Priority was given to publications focusing on the end of treatment or the discontinuation of clinical studies or trials. RESULTS: We identified three primary groups of ethical challenges: patient-centric challenges, challenges faced by the research and physician team, and manufacturer-related issues. Further analysis highlights the importance of initiating early, transparent discussions regarding trial cessation protocols, ensuring that all stakeholders-patients, healthcare providers, researchers, and manufacturers-are equitably considered. Additionally, we found a discrepancy between current discontinuation strategies and international ethical guidelines. To address this, we emphasize the ethical obligation to establish comprehensive exit strategies that align with the principles in the Declaration of Helsinki and the CIOMS/WHO guidelines. CONCLUSION: Our findings highlight the need for increased attention to the ethical and practical aspects of exit strategies and encourage further empirical research to address gaps in current practices. This would ensure that the discontinuation of IND trials is handled with ethical rigor, prioritizing the interests and well-being of all stakeholders involved.

13.
J Neurosurg ; : 1-9, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39332035

RESUMO

OBJECTIVE: The lateral spread response (LSR) is an important electrophysiological sign that predicts successful decompression in patients undergoing microvascular decompression (MVD) for hemifacial spasm (HFS). However, LSRs do not consistently correlate with clinical outcomes, and there are cases in which LSRs are absent. In this study, the authors identified a unique pattern on facial nerve electromyography (EMG) when the root exit zone (REZ) is touched. This distinctive EMG pattern, which the authors coined the "Sang-ku sign" (SKS), could aid in identifying the offending vessel on the REZ, even in the absence of LSRs. METHODS: Between November 2022 and August 2023, the authors analyzed EMG findings from 185 patients undergoing MVD for HFS. Bipolar stimulation electrodes were placed at the marginal mandibular branch, and recordings were obtained from the frontalis and orbicularis oris muscles. Additionally, stimulation electrodes were placed at the temporal branch, and recordings were obtained from the oris and mentalis muscles. The authors statistically analyzed the presence of SKS and its association with demographic, surgical, clinical outcomes, and anatomical factors. RESULTS: The authors observed a brief, burst-like wave pattern arising from all recorded muscle branches when Teflon felt was placed between the REZ and the facial nerve. This EMG pattern, the SKS, was found in 164 patients (88.6%). Among the factors analyzed, only patient age showed a significant association with the presence of the SKS in univariate analysis (p = 0.007). The presence of the SKS was significantly associated with predicting the disappearance of LSRs (p = 0.045). Clinical outcomes were favorable (99% at the last follow-up) in all cases; thus, no positive correlation was observed in the existence of the SKS and LSRs. CONCLUSIONS: The SKS could serve as an excellent guide for the facial nerve REZ during surgery. Given that HFS results from abnormal vascular contact on the REZ, this finding plays a crucial role in ensuring surgical success. Alongside LSRs, the SKS could provide valuable insights for neurosurgeons.

14.
Cureus ; 16(8): e67997, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39347122

RESUMO

Introduction Peritoneal dialysis (PD) is an essential home-based treatment for end-stage kidney disease, known for enhancing patients' quality of life and being more cost-effective compared to hemodialysis. However, in Singapore, PD education lacks of standardization, with each unit adopting varied methods based on their own experiences and resources. To address this, our hospital developed a tailored four-day PD training program guided by the International Society for Peritoneal Dialysis guidelines, adapted to meet local needs and resource availability. Methodology This study employed a retrospective cohort design, including all incident adult patients aged 18 years and above who initiated PD at our hospital from September 2018 to July 2023. Data on PD dropout rates and PD-related infection rates, such as PD peritonitis and exit site infection rates, were obtained from electronic medical records. Results This study comprised 99 patients who began PD and completed their PD training program at our hospital between September 2018 and July 2023. Our tailored PD training program successfully reduced dropout rates and maintained infection rates within the International Society for Peritoneal Dialysis guidelines. Specifically, exit site infection rates fluctuated between 0.18 and 0.29 episodes per year, PD peritonitis rates ranged from 0.2 to 0.26 episodes per patient-year, and dropout rates significantly improved from 40% in 2019 to 7% in 2023 (OR = 0.45, 95% CI = 0.49 to 0.84, p = 0.010). Conclusions The tailored PD training program at our hospital effectively reduced PD-related infections and dropout rates among end-stage kidney disease patients. These findings suggest that structured, locally adapted training programs can substantially improve patient outcomes in PD.

15.
Autophagy ; : 1-19, 2024 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-39177202

RESUMO

Starvation- or stress-induced phosphatidylinositol 3-phosphate (PtdIns3P/PI3P) production at the endoplasmic reticulum (ER) subdomains organizes phagophore assembly and autophagosome formation. Coat protein complex II (COPII) vesicles budding from ER exit site (ERES) also contribute to autophagosome formation. Whether any PtdIns3P phosphatase functions at ERES to inhibit macroautophagy/autophagy is unknown. Here we report Myotubularin 2 (MTM2) of Arabidopsis as a PtdIns3P phosphatase that localizes to ERES and negatively regulates autophagy. MTM2 binds PtdIns3P with its PH-GRAM domain in vitro and acts toward PtdIns3P in vivo. Transiently expressed MTM2 colocalizes with ATG14b, a subunit of the phosphatidylinositol 3-kinase (PtdIns3K) complex, and overexpression of MTM2 blocks autophagic flux and causes over-accumulation of ATG18a, ATG5, and ATG8a. The mtm2 mutant has higher levels of autophagy and is more tolerant to starvation, whereas MTM2 overexpression leads to reduced autophagy and sensitivity to starvation. The phenotypes of mtm2 are suppressed by ATG2 mutation, suggesting that MTM2 acts upstream of ATG2. Importantly, MTM2 does not affect the endosomal functions of PtdIns3P. Instead, MTM2 specifically colocalizes with COPII coat proteins and is cradled by the ERES-defining protein SEC16. MTM2 interacts with SEC23A with its phosphatase domain and inhibits COPII-mediated protein secretion. Finally, a role for MTM2 in salt stress response is uncovered. mtm2 resembles the halophyte Thellungiella salsuginea in its efficient vacuolar compartmentation of Na+, maintenance of chloroplast integrity, and timely regulation of autophagy-related genes. Our findings reveal a balance between PtdIns3P synthesis and turnover in autophagosome formation, and provide a new link between autophagy and COPII function.Abbreviations: ATG: autophagy related; BFA: brefeldin A; BiFC: bimolecular fluorescence complementation; CHX: cycloheximide; ConA: concanamycin A; COPII: coat protein complex II; ER: endoplasmic reticulum; ERES: ER exit site; MS: Murashige and Skoog; MTM: myotubularin; MVB: multivesicular body; PAS: phagophore assembly site; PI: phosphoinositide; TEM: transmission electron microscopy; WT: wild-type.

16.
BMC Nephrol ; 25(1): 273, 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39187762

RESUMO

BACKGROUND: Refractory exit-site infections (ESIs) and tunnel infections (TIs) are challenging complications for patients undergoing peritoneal dialysis (PD). This study compared the outcomes of surgical intervention, notably the cuff-shaving (CS) procedure coupled with negative-pressure wound therapy (NPWT), and conservative management strategies for patients with refractory ESI and TI. METHODS: We retrospectively reviewed patients who underwent PD at our center, focusing on the incidence and management of ESI and TI. We evaluated and compared treatment outcomes, including ESI scores, frequency of ESI and/or TI, identification of causative microorganisms, and duration of catheter survival or time until removal. RESULTS: We identified 97 episodes of catheter-related ESI and/or TI across 71 patients with an incidence rate of 0.15 episodes per patient-year. Of the 23 patients with refractory ESI and/or TI, surgical intervention was performed in 8, while 15 chose conservative management. In the one-month follow-up, patients who underwent CS combined with NPWT showed no complications such as leakage, and their local symptoms resolved completely. The mean PD catheter survival time was significantly longer in the surgical group (29.38 ± 7.25 months) than in the conservative group (7.86 ± 2.13 months). Surgical intervention demonstrated a significantly higher therapeutic efficacy and extended catheter survival. CONCLUSIONS: The combination of CS and NPWT as a surgical approach is crucial for eradicating infectious foci and significantly improving the longevity of PD catheter function. This integrated surgical strategy offers a promising solution for the management of refractory ESI and TI in patients undergoing PD.


Assuntos
Infecções Relacionadas a Cateter , Tratamento de Ferimentos com Pressão Negativa , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Infecções Relacionadas a Cateter/terapia , Idoso , Diálise Peritoneal , Resultado do Tratamento , Cateteres de Demora/efeitos adversos , Adulto , Tratamento Conservador
17.
Inn Med (Heidelb) ; 2024 Aug 21.
Artigo em Alemão | MEDLINE | ID: mdl-39167189

RESUMO

The case of a 72-year-old female patient with arrhythmogenic syncope associated with a combination therapy of flecainide and lacosamide is presented. The authors believe in an additive effect of both drugs on myocardial voltage-gated sodium channels with extraordinary QRS widening, exit block with temporary pacing and complete reversibility through infusion of sodium bicarbonate as bail-out therapy.

18.
ACS Appl Mater Interfaces ; 16(34): 45671-45677, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39137151

RESUMO

Electronic devices continue to shrink in size while increasing in performance, making excess heat dissipation challenging. Traditional thermal interface materials (TIMs) such as thermal grease and pads face limitations in thermal conductivity and stability, particularly as devices scale down. Carbon nanotubes (CNTs) have emerged as promising candidates for TIMs because of their exceptional thermal conductivity and mechanical properties. However, the thermal conductivity of CNT films decreases when integrated into devices due to defects and bundling effects. This study employs a novel cross-sectional approach combining high-vacuum scanning thermal microscopy (SThM) with beam-exit cross-sectional polishing (BEXP) to investigate the nanoscale morphology and thermal properties of vertically aligned CNT bundles at low and room temperatures. Using appropriate thermal transport models, we extracted effective thermal conductivities of the vertically aligned nanotubes and obtained 4 W m-1 K-1 at 200 K and 37 W m-1 K-1 at 300 K. Additionally, non-negligible lateral thermal conductance between CNT bundles suggests more complex heat transfer mechanisms in these structures. These findings provide unique insights into nanoscale thermal transport in CNT bundles, which is crucial for optimizing novel thermal management strategies.

19.
Micron ; 186: 103705, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39186889

RESUMO

A study on DPC and iDPC images of crystals is achieved with simulation. It highlights the use of electron wave intensity distribution to visualize the dynamic effect on DPC and iDPC contrasts. Electron waves near heavy atoms exhibit significant oscillations and rapid intensity decay. This oscillation causes DPC and iDPC signal inversion. Bloch wave theory is used to derive DPC and iDPC intensity distributions, elucidating the impact of dynamic effect on the contrast.

20.
J Plankton Res ; 46(4): 439-451, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39091692

RESUMO

Respiration of lipids by copepods during diapause (overwintering dormancy) contributes to ocean carbon sequestration via the seasonal lipid pump (SLP). Parameterizing this flux in predictive models requires a mechanistic understanding of how life history adaptation in copepods shapes their timing of exit from diapause. We investigate the optimal phenology of Calanus finmarchicus in the Norwegian Sea using an individual-based model in which diapause exit is represented as a trait characterized by phenotypic mean and variance. Without interannual variability, optimal exit correlated with the onset of the spring phytoplankton bloom and phenotypic variance was of no benefit. In contrast, copepods endured reduced fitness and adopted bet-hedging strategies when exposed to interannual variability in bloom timing and predation: later exit from diapause and phenotypic variance maintained adult numbers in anomalous late-bloom years. Exit nevertheless remained well before the peak of the bloom which is a favorable strategy when low predation early in the year enhances survival of eggs and early developmental stages. Our work highlights the complex interactions between C. finmarchicus and its environment and the need for improved understanding of bet-hedging strategies and the cues of diapause exit to progress the representation of the SLP in global biogeochemical models.

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