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1.
Imaging Sci Dent ; 54(2): 121-127, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38948184

RESUMO

Purpose: Preoperative identification of the intraosseous posterior superior alveolar artery (PSAA) is critical when planning sinus surgery. This study was conducted to determine the distance between the cementoenamel junction and the PSAA, as well as to identify factors influencing the detection of the PSAA on cone-beam computed tomography (CBCT). Materials and Methods: In total, 254 CBCT scans of maxillary sinuses, acquired with 2 different scanners, were examined to identify the PSAA. The distance from the cementoenamel junction (CEJ) to the PSAA was recorded at each maxillary posterior tooth position. Binomial logistic regression and multiple linear regression were employed to evaluate the effects of scanner type, CBCT parameters, sex, and age on PSAA detection and CEJ-PSAA distance, respectively. P-values less than 0.05 were considered to indicate statistical significance. Results: The mean CEJ-PSAA distances at the second molar, first molar, second premolar, and first premolar positions were 17.0±4.0 mm, 21.8±4.1 mm, 19.5±4.7 mm, and 19.9±4.9 mm for scanner 1, respectively, and 17.3±3.5 mm, 16.9±4.3 mm, 18.5±4.1 mm, and 18.4±4.3 mm for scanner 2. No independent variable significantly influenced PSAA detection. However, tooth position (b=-0.67, P<0.05) and scanner type (b=-1.3, P<0.05) were significant predictors of CEJ-PSAA distance. Conclusion: CBCT-based estimates of CEJ-PSAA distance were comparable to those obtained in previous studies involving cadavers, CT, and CBCT. The type of CBCT scanner may slightly influence this measurement. No independent variable significantly impacted PSAA detection.

2.
R I Med J (2013) ; 107(8): 39-45, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39058988

RESUMO

BACKGROUND: Interpersonal violence is a significant contributor to global morbidity, and affects young adults, particularly males. In Kenya, injuries, including those from interpersonal violence, are a leading cause of emergency department (ED) visits. OBJECTIVE: This study aims to evaluate the frequency, demographics, and types of injuries caused by interpersonal and intimate partner violence among patients presenting to the Kenyatta National Hospital (KNH) ED in Nairobi, Kenya. METHODS: This was a prospective cross-sectional study among injured adult patients presenting to the KNH ED. RESULTS: Of 665 enrolled patients, 82% identified as male and the median age was 30 years. Among enrollees, 257 (39%) reported ever having experienced physical, sexual, and/or emotional violence. Seventy-one patients reported a history of intimate partner violence; more than half had experienced intimate partner violence within the past 12 months. CONCLUSIONS: Research on interpersonal injuries in ED settings is lacking, but data from a single Kenyan ED reveals a significant portion of injured patients with a history of interpersonal and intimate partner violence.


Assuntos
Serviço Hospitalar de Emergência , Violência por Parceiro Íntimo , Ferimentos e Lesões , Humanos , Quênia/epidemiologia , Masculino , Feminino , Adulto , Violência por Parceiro Íntimo/estatística & dados numéricos , Violência por Parceiro Íntimo/psicologia , Estudos Transversais , Ferimentos e Lesões/epidemiologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Estudos Prospectivos , Adulto Jovem , Pessoa de Meia-Idade , Adolescente
3.
Open Access Emerg Med ; 16: 167-181, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39045605

RESUMO

Compassion fatigue (CF), or loss of ability to empathize or feel compassion for others for whom one cares, is a growing concern for emergency physicians (EP). EPs, by the nature of their jobs, work under unpredictable conditions at odd hours with high levels of exposure to traumatic events. They are placed under substantial psychological, physical, and cognitive pressure, with little opportunity to recover or reflect. CF occurs when this workplace stress leads to feelings of being overwhelmed, helpless, unsupported, and unable to cope. Additionally, primary traumatic stress from threats of workplace violence and secondary traumatic stress (STS) from witnessing the suffering of others increase the likelihood of developing CF. Unchecked, this progression to CF causes reduction in quality of care to patients, reduction in patient satisfaction, increased levels of EP depression and anxiety, increased levels of EP substance use, and increased attrition from the specialty. To truly improve CF, individuals and organizations should be aware of the contributors to CF: namely, emotional exhaustion, depersonalization, primary and STS, and personal achievement. EPs should maximize their resilience to CF by using cognitive behavioral techniques and mindfulness, taking care of their physical health, seeking meaning and development within their work, developing hobbies outside of work, and creating boundaries between work and home. Organizations should actively address the known drivers of physician burnout: workload and job demands, efficiency and resources, meaning in work, culture and values, control and flexibility, work community, and work-life integration. Organizations should also provide adequate safety within facilities to reduce the threat of primary trauma and should supply adequate support and destigmatization for post-traumatic symptoms for EPs suffering from STS.

4.
Nat Commun ; 15(1): 6170, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39043654

RESUMO

Engineering stabilized proteins is a fundamental challenge in the development of industrial and pharmaceutical biotechnologies. We present Stability Oracle: a structure-based graph-transformer framework that achieves SOTA performance on accurately identifying thermodynamically stabilizing mutations. Our framework introduces several innovations to overcome well-known challenges in data scarcity and bias, generalization, and computation time, such as: Thermodynamic Permutations for data augmentation, structural amino acid embeddings to model a mutation with a single structure, a protein structure-specific attention-bias mechanism that makes transformers a viable alternative to graph neural networks. We provide training/test splits that mitigate data leakage and ensure proper model evaluation. Furthermore, to examine our data engineering contributions, we fine-tune ESM2 representations (Prostata-IFML) and achieve SOTA for sequence-based models. Notably, Stability Oracle outperforms Prostata-IFML even though it was pretrained on 2000X less proteins and has 548X less parameters. Our framework establishes a path for fine-tuning structure-based transformers to virtually any phenotype, a necessary task for accelerating the development of protein-based biotechnologies.


Assuntos
Mutação , Estabilidade Proteica , Proteínas , Termodinâmica , Proteínas/genética , Proteínas/química , Engenharia de Proteínas/métodos , Modelos Moleculares , Algoritmos , Redes Neurais de Computação , Conformação Proteica , Biologia Computacional/métodos
5.
J Neurotrauma ; 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-38984940

RESUMO

The International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) model is a widely recognized prognostic model applied after traumatic brain injury (TBI). However, it was developed with patient cohorts that may not reflect modern practice patterns in North America. We analyzed data from two sources: the placebo arm of the phase II double-blinded, multicenter, randomized controlled trial Prehospital Tranexamic Acid for TBI (TXA) cohort and an observational cohort with similar inclusion/exclusion criteria (Predictors of Low-risk Phenotypes after Traumatic Brain Injury Incorporating Proteomic Biomarker Signatures [PROTIPS] cohort). All three versions of the IMPACT model-core, extended, and laboratory-were evaluated for 6-month mortality (Glasgow Outcome Scale Extended [GOSE] = 1) and unfavorable outcomes (GOSE = 1-4). Calibration (intercept and slope) and discrimination (area under the receiver operating characteristic curve [ROC-AUC]) were used to assess model performance. We then compared three model updating methods-recalibration in the large, logistic recalibration, and coefficient update-with the best update method determined by likelihood ratio tests. In our calibration analysis, recalibration improved both intercepts and slopes, indicating more accurate predicted probabilities when recalibration was done. Discriminative performance of the IMPACT models, measured by AUC, showed mortality prediction ROCs between 0.61 and 0.82 for the TXA cohort, with the coefficient updated Lab model achieving the highest at 0.84. Unfavorable outcomes had lower AUCs, ranging from 0.60 to 0.79. Similarly, in the PROTIPS cohort, AUCs for mortality ranged from 0.75 to 0.82, with the coefficient updated Lab model also showing superior performance (AUC 0.84). Unfavorable outcomes in this cohort presented AUCs from 0.67 to 0.73, consistently lower than mortality predictions. The closed testing procedure using likelihood ratio tests consistently identified the coefficient update model as superior, outperforming the original and recalibrated models across all cohorts. In our comprehensive evaluation of the IMPACT model, the coefficient updated models were the best performing across all cohorts through a structured closed testing procedure. Thus, standardization of model updating procedures is needed to reproducibly determine the best performing versions of IMPACT that reflect the specific characteristics of a dataset.

6.
Cell Chem Biol ; 31(7): 1305-1323.e9, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39029456

RESUMO

K2P potassium channels regulate excitability by affecting cellular resting membrane potential in the brain, cardiovascular system, immune cells, and sensory organs. Despite their important roles in anesthesia, arrhythmia, pain, hypertension, sleep, and migraine, the ability to control K2P function remains limited. Here, we describe a chemogenetic strategy termed CATKLAMP (covalent activation of TREK family K+ channels to clamp membrane potential) that leverages the discovery of a K2P modulator pocket site that reacts with electrophile-bearing derivatives of a TREK subfamily small-molecule activator, ML335, to activate the channel irreversibly. We show that CATKLAMP can be used to probe fundamental aspects of K2P function, as a switch to silence neuronal firing, and is applicable to all TREK subfamily members. Together, our findings exemplify a means to alter K2P channel activity that should facilitate molecular and systems level studies of K2P function and enable the search for new K2P modulators.


Assuntos
Canais de Potássio de Domínios Poros em Tandem , Humanos , Canais de Potássio de Domínios Poros em Tandem/metabolismo , Canais de Potássio de Domínios Poros em Tandem/genética , Animais , Células HEK293 , Camundongos , Potenciais da Membrana/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/efeitos dos fármacos , Ratos
7.
Proc Natl Acad Sci U S A ; 121(28): e2401579121, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38968123

RESUMO

Iron is an essential element for life owing to its ability to participate in a diverse array of oxidation-reduction reactions. However, misregulation of iron-dependent redox cycling can also produce oxidative stress, contributing to cell growth, proliferation, and death pathways underlying aging, cancer, neurodegeneration, and metabolic diseases. Fluorescent probes that selectively monitor loosely bound Fe(II) ions, termed the labile iron pool, are potentially powerful tools for studies of this metal nutrient; however, the dynamic spatiotemporal nature and potent fluorescence quenching capacity of these bioavailable metal stores pose challenges for their detection. Here, we report a tandem activity-based sensing and labeling strategy that enables imaging of labile iron pools in live cells through enhancement in cellular retention. Iron green-1 fluoromethyl (IG1-FM) reacts selectively with Fe(II) using an endoperoxide trigger to release a quinone methide dye for subsequent attachment to proximal biological nucleophiles, providing a permanent fluorescent stain at sites of elevated labile iron. IG1-FM imaging reveals that degradation of the major iron storage protein ferritin through ferritinophagy expands the labile iron pool, while activation of nuclear factor-erythroid 2-related factor 2 (NRF2) antioxidant response elements (AREs) depletes it. We further show that lung cancer cells with heightened NRF2 activation, and thus lower basal labile iron, have reduced viability when treated with an iron chelator. By connecting labile iron pools and NRF2-ARE activity to a druggable metal-dependent vulnerability in cancer, this work provides a starting point for broader investigations into the roles of transition metal and antioxidant signaling pathways in health and disease.


Assuntos
Elementos de Resposta Antioxidante , Ferro , Humanos , Ferro/metabolismo , Corantes Fluorescentes/química , Fator 2 Relacionado a NF-E2/metabolismo , Ferritinas/metabolismo , Estresse Oxidativo , Oxirredução , Linhagem Celular Tumoral , Antioxidantes/metabolismo
8.
Proc Natl Acad Sci U S A ; 121(28): e2402872121, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38968126

RESUMO

Bioengineering of plant immune receptors has emerged as a key strategy for generating novel disease resistance traits to counteract the expanding threat of plant pathogens to global food security. However, current approaches are limited by rapid evolution of plant pathogens in the field and may lack durability when deployed. Here, we show that the rice nucleotide-binding, leucine-rich repeat (NLR) immune receptor Pik-1 can be engineered to respond to a conserved family of effectors from the multihost blast fungus pathogen Magnaporthe oryzae. We switched the effector binding and response profile of the Pik NLR from its cognate rice blast effector AVR-Pik to the host-determining factor pathogenicity toward weeping lovegrass 2 (Pwl2) by installing a putative host target, OsHIPP43, in place of the native integrated heavy metal-associated domain (generating Pikm-1OsHIPP43). This chimeric receptor also responded to other PWL alleles from diverse blast isolates. The crystal structure of the Pwl2/OsHIPP43 complex revealed a multifaceted, robust interface that cannot be easily disrupted by mutagenesis, and may therefore provide durable, broad resistance to blast isolates carrying PWL effectors in the field. Our findings highlight how the host targets of pathogen effectors can be used to bioengineer recognition specificities that have more robust properties compared to naturally evolved disease resistance genes.


Assuntos
Proteínas Fúngicas , Proteínas NLR , Oryza , Doenças das Plantas , Proteínas de Plantas , Oryza/microbiologia , Oryza/imunologia , Doenças das Plantas/microbiologia , Doenças das Plantas/imunologia , Proteínas NLR/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/imunologia , Proteínas de Plantas/genética , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/química , Proteínas Fúngicas/imunologia , Interações Hospedeiro-Patógeno/imunologia , Resistência à Doença/imunologia , Imunidade Vegetal , Bioengenharia/métodos , Magnaporthe/imunologia , Magnaporthe/genética , Magnaporthe/metabolismo , Ligação Proteica , Receptores Imunológicos/metabolismo , Ascomicetos
9.
PM R ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38967539

RESUMO

As health care attempts to bridge the gap between evidence and practice, the concept of the learning health system (LHS) is becoming increasingly relevant. LHS integrates evidence with health systems data, driving health care quality and outcomes through updates in policy, practice, and care delivery. In addition, LHS research is becoming critically important as there are several initiatives underway to increase research capacity, expertise, and implementation, including attempts to stimulate increasing numbers of LHS researchers. Physical Medicine & Rehabilitation (PM&R) physicians (physiatrists), nurses, therapists (physical therapists, occupational therapists, speech therapists, clinical psychologists), and scientists are affiliated with LHSs. As LHS research expands in health care systems, better awareness and understanding of LHSs and LHS research competencies are key for rehabilitation professionals including physiatrists. To address this need, the Agency of Healthcare Research and Quality (AHRQ) identified 33 core competencies, grouped into eight domains, for training LHS researchers. The domains are: (1) Systems Science; (2) Research Questions and Standards of Scientific Evidence; (3) Research Methods; (4) Informatics; (5) Ethics of Research and Implementation in Health Systems; (6) Improvement and Implementation Science; (7) Engagement, Leadership, and Research Management; and the recently added (8) Health and Healthcare Equity and Justice. The purpose of this commentary is to define LHS and its relevance to physiatrists, present the role of implementation science (IS) in LHSs and application of IS principles to design LHSs, illustrate current LHS research in rehabilitation, and discuss potential solutions to improve awareness and to stimulate interest in LHS research and IS among physiatrists in LHSs.

10.
R Soc Open Sci ; 11(5): 240539, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-39076789

RESUMO

For social groups to form and be stable over time, animals must develop strategies to cope with conflict among group members. Animals may behave submissively either by fleeing from an aggressor, or by signalling submission. The use of these two submissive responses may vary depending on the social and ecological context. Group size is a key aspect of social context for group living animals, as individuals in smaller groups may respond to aggression differently than those from larger groups. Here, we examine the relationship between group size and submissive behaviour in a cooperatively breeding fish, the daffodil cichlid (Neolamprologus pulcher). We found that subordinate fish showed similar levels of submission signals in response to dominant aggression in larger and smaller groups, however, subordinates from larger groups were less likely to flee from dominant aggression than those in smaller groups. Subordinates in larger groups also showed more digging behaviour which may be also used to avoid conflict with the dominant group members. Our data show that social context affects submissive behaviour in a cooperatively breeding fish.

11.
Neurotrauma Rep ; 5(1): 686-698, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39071986

RESUMO

Translation of spinal cord injury (SCI) therapeutics from pre-clinical animal studies into human studies is challenged by effect size variability, irreproducibility, and misalignment of evidence used by pre-clinical versus clinical literature. Clinical literature values reproducibility, with the highest grade evidence (class 1) consisting of meta-analysis demonstrating large therapeutic efficacy replicating across multiple studies. Conversely, pre-clinical literature values novelty over replication and lacks rigorous meta-analyses to assess reproducibility of effect sizes across multiple articles. Here, we applied modified clinical meta-analysis methods to pre-clinical studies, comparing effect sizes extracted from published literature to raw data on individual animals from these same studies. Literature-extracted data (LED) from numerical and graphical outcomes reported in publications were compared with individual animal data (IAD) deposited in a federally supported repository of SCI data. The animal groups from the IAD were matched with the same cohorts in the LED for a direct comparison. We applied random-effects meta-analysis to evaluate predictors of neuroconversion in LED versus IAD. We included publications with common injury models (contusive injuries) and standardized end-points (open field assessments). The extraction of data from 25 published articles yielded n = 1841 subjects, whereas IAD from these same articles included n = 2441 subjects. We observed differences in the number of experimental groups and animals per group, insufficient reporting of dropout animals, and missing information on experimental details. Meta-analysis revealed differences in effect sizes across LED versus IAD stratifications, for instance, severe injuries had the largest effect size in LED (standardized mean difference [SMD = 4.92]), but mild injuries had the largest effect size in IAD (SMD = 6.06). Publications with smaller sample sizes yielded larger effect sizes, while studies with larger sample sizes had smaller effects. The results demonstrate the feasibility of combining IAD analysis with traditional LED meta-analysis to assess effect size reproducibility in SCI.

12.
Nat Protoc ; 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39039320

RESUMO

Rare cells have an important role in development and disease, and methods for isolating and studying cell subsets are therefore an essential part of biology research. Such methods traditionally rely on labeled antibodies targeted to cell surface proteins, but large public databases and sophisticated computational approaches increasingly define cell subsets on the basis of genomic, epigenomic and transcriptomic sequencing data. Methods for isolating cells on the basis of nucleic acid sequences powerfully complement these approaches by providing experimental access to cell subsets discovered in cell atlases, as well as those that cannot be otherwise isolated, including cells infected with pathogens, with specific DNA mutations or with unique transcriptional or splicing signatures. We recently developed a nucleic acid cytometry platform called 'focused interrogation of cells by nucleic acid detection and sequencing' (FIND-seq), capable of isolating rare cells on the basis of RNA or DNA markers, followed by bulk or single-cell transcriptomic analysis. This platform has previously been used to characterize the splicing-dependent activation of the transcription factor XBP1 in astrocytes and HIV persistence in memory CD4 T cells from people on long-term antiretroviral therapy. Here, we outline the molecular and microfluidic steps involved in performing FIND-seq, including protocol updates that allow detection and whole transcriptome sequencing of rare HIV-infected cells that harbor genetically intact virus genomes. FIND-seq requires knowledge of microfluidics, optics and molecular biology. We expect that FIND-seq, and this comprehensive protocol, will enable mechanistic studies of rare HIV+ cells, as well as other cell subsets that were previously difficult to recover and sequence.

13.
Trauma Surg Acute Care Open ; 9(1): e001501, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39081460

RESUMO

Objectives: An estimated 14-23% of patients with traumatic brain injury (TBI) incur multiple lifetime TBIs. The relationship between prior TBI and outcomes in patients with moderate to severe TBI (msTBI) is not well delineated. We examined the associations between prior TBI, in-hospital mortality, and outcomes up to 12 months after injury in a prospective US msTBI cohort. Methods: Data from hospitalized subjects with Glasgow Coma Scale score of 3-12 were extracted from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study (enrollment period: 2014-2019). Prior TBI with amnesia or alteration of consciousness was assessed using the Ohio State University TBI Identification Method. Competing risk regressions adjusting for age, sex, psychiatric history, cranial injury and extracranial injury severity examined the associations between prior TBI and in-hospital mortality, with hospital discharged alive as the competing risk. Adjusted HRs (aHR (95% CI)) were reported. Multivariable logistic regressions assessed the associations between prior TBI, mortality, and unfavorable outcome (Glasgow Outcome Scale-Extended score 1-3 (vs. 4-8)) at 3, 6, and 12 months after injury. Results: Of 405 acute msTBI subjects, 21.5% had prior TBI, which was associated with male sex (87.4% vs. 77.0%, p=0.037) and psychiatric history (34.5% vs. 20.7%, p=0.010). In-hospital mortality was 10.1% (prior TBI: 17.2%, no prior TBI: 8.2%, p=0.025). Competing risk regressions indicated that prior TBI was associated with likelihood of in-hospital mortality (aHR=2.06 (1.01-4.22)), but not with hospital discharged alive. Prior TBI was not associated with mortality or unfavorable outcomes at 3, 6, and 12 months. Conclusions: After acute msTBI, prior TBI history is independently associated with in-hospital mortality but not with mortality or unfavorable outcomes within 12 months after injury. This selective association underscores the importance of collecting standardized prior TBI history data early after acute hospitalization to inform risk stratification. Prospective validation studies are needed. Level of evidence: IV. Trial registration number: NCT02119182.

14.
Artigo em Inglês | MEDLINE | ID: mdl-39019488

RESUMO

OBJECTIVE: We sought to elicit key informant (KI) perspectives regarding decisional needs of Veterans with mild traumatic brain injury (mTBI) who are initiating insomnia disorder and obstructive sleep apnea (OSA) treatment within the Veterans Health Administration (VHA) Polytrauma/TBI System of Care (PSC). Specifically, we sought to understand: (1) information regarding treatment options that Veterans with mTBI require in order to make an informed decision; and (2) values used to guide decision-making (ie, personally meaningful aspects of the decision used to compare treatment options). SETTING: Nationwide VHA PSC sites. PARTICIPANTS: Clinicians included VHA providers and policymakers involved in the management of mTBI and/or sleep disorders in the VHA PSC (n = 29). Veterans included those with a clinician-confirmed mTBI who received care for insomnia disorder and/or OSA within the past year (n = 20). DESIGN: Semi-structured interviews with the 49 KIs were recorded and transcribed verbatim. Themes were identified using a descriptive and interpretive approach to qualitative analysis. MAIN MEASURES: Not applicable. RESULTS: Informational needs identified by both KI groups included information regarding outcomes and downsides of treatment, accessible delivery, treatment candidates, description of diagnosis, and level of commitment. Values used to guide decision-making for both insomnia disorder and OSA treatment included benefits, downsides, and availability of treatments. Values used to decide on insomnia treatments alone included time commitment, intrinsic management of sleep, beliefs regarding mental health treatment, and time course of benefit. Values used to decide on OSA treatment alone included intrusiveness of the treatment, appearance, and impact on bed partners. CONCLUSIONS: The current study revealed the decisional needs of Veterans with mTBI who are initiating sleep disorder treatment. Findings can inform the development of decision aids and other efforts aimed at promoting patient-centered management of comorbid mTBI and sleep disorders, thereby improving care quality and clinical outcomes.

15.
J Urol ; : 101097JU0000000000004099, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38865696

RESUMO

PURPOSE: Reoperative partial nephrectomy (RePN) offers several advantages for the treatment of recurrent, multifocal renal masses. RePN has been previously demonstrated to be technically feasible and delay the need for renal replacement therapy. However, there is still inherent complexity and known risks to reoperative nephrectomy. We studied the largest population of RePNs to characterize renal functional outcomes and the likelihood of intra- and postoperative complications. MATERIALS AND METHODS: Query of an institutional surgical registry was conducted. Demographic data, serum creatinine for estimated glomerular filtration rate (eGFR), and protein dipstick results were assessed within 1 week prior to surgery, and postoperative function assessments were studied within a year of surgery. RePN was defined as serial surgical resection of the ipsilateral renal unit. RESULTS: A total of 1131 partial nephrectomies performed on 663 patients at a single center were retrospectively evaluated. In reoperative cases, median number of operations per renal unit was 2 (range: 2-6). There was a stepwise decline in eGFR with an average decline of 6.1 with each RePN. With each subsequent nephrectomy, surgical duration, estimated blood loss, and incidence of preoperative anemia increased. Postoperative eGFR showed a significant positive association with preoperative eGFR, while negative associations were found with age, number of previous ipsilateral partial nephrectomies, number of tumors, and largest tumor size. High-grade complications were associated with the number of ipsilateral partial nephrectomies, tumor count, and tumor size. Robotic or laparoscopic procedures exhibited a likelihood of grade 3 or greater complications compared to open surgery. CONCLUSION: RePN contributes to renal dysfunction and an increased risk of surgical complications. Intraoperative blood loss and surgical duration increase with subsequent nephrectomy. Such risks are dependent on the number of prior operative interventions on the kidney, suggesting a stepwise progression of surgical morbidity.

16.
JCO Glob Oncol ; 10: e2300403, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38870437

RESUMO

PURPOSE: Prostate cancer disproportionately affects men of African descent, yet their representation in tissue-based studies is limited. This multinational, multicenter pilot study aims to establish the groundwork for collaborative research on prostate cancer in sub-Saharan Africa. METHODS: The Men of African Descent and Carcinoma of the Prostate network formed a pathologist working group representing eight institutions in five African countries. Formalin-fixed paraffin-embedded prostate tissue specimens were collected from Senegal, Nigeria, and Ghana. Histology slides were produced and digitally scanned. A central genitourinary pathologist (P.L.) and eight African general pathologists reviewed anonymized digital whole-slide images for International Society of Urological Pathology grade groups and other pathologic parameters. Discrepancies were re-evaluated, and consensus grading was assigned. A virtual training seminar on prostate cancer grading was followed by a second assessment on a subcohort of the same tissue set. RESULTS: Of 134 tissue blocks, 133 had evaluable tissue; 13 lacked cancer evidence, and four were of insufficient quality. Post-training, interobserver agreement for grade groups improved to 56%, with a median Cohen's quadratic weighted kappa of 0.83 (mean, 0.74), compared with an initial 46% agreement and a quadratic weighted kappa of 0.77. Interobserver agreement between African pathologist groups was 40%, with a quadratic weighted kappa of 0.66 (95% CI, 0.51 to 0.76). African pathologists tended to overgrade (36%) more frequently than undergrade (18%) compared with the reference genitourinary pathologist. Interobserver variability tended to worsen with a decrease in tissue quality. CONCLUSION: Tissue-based studies on prostate cancer in men of African descent are essential for a better understanding of this common disease. Standardized tissue handling protocols are crucial to ensure good tissue quality and data. The use of digital slide imaging can enhance collaboration among pathologists in multinational, multicenter studies.


Assuntos
Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/patologia , África Subsaariana , Projetos Piloto , Gradação de Tumores
17.
Surgery ; 176(2): 477-484, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38839431

RESUMO

BACKGROUND: Benefits of thoracic enhanced recovery after surgery programs have been described. However, there is ongoing discussion on the importance of full protocol compliance. The objective of this study was to determine whether strict adherence to an enhanced recovery after surgery protocol leads to further improvement in outcomes compared with less strict compliance. METHODS: This was a multihospital prospective cohort study of all consecutive anatomic lung resection patients on the thoracic enhanced recovery after surgery pathway from May 2021 to March 2023, with comparison with a historical control from January 2019 to April 2021. Compliance to 5 key protocol elements was tracked. Patients were grouped into high- and low-compliance cohorts, defined as adherence to 4-5/5 or 0-3/5 elements, respectively. The primary outcome was overall morbidity; secondary outcomes included cardiac, respiratory, and infectious morbidity and length of stay. RESULTS: Of the 960 patients, 429 (44.7%) were enhanced recovery after surgery patients and 531 (55.3%) were in the historical control group. Across all patients, 250 (26.0%) were considered high compliance and 710 (74.0%) were considered low compliance. After adjustment for enhanced recovery after surgery status and confounders, the association between high compliance and improved outcomes persisted for all but infectious morbidity. Compared with low compliance, high compliance was associated with decreased odds of any morbidity (0.41 [95% CI, 0.22-0.77]), cardiac morbidity (0.31 [0.11-0.91]), respiratory morbidity (0.46 [0.23-0.90]) and decreased length of stay (0.38 [0.18-0.87]). CONCLUSION: Enhanced recovery after surgery protocols improve outcomes after anatomic lung resection. Increasing compliance to individual elements (>80%) further improves patient outcomes. Continued efforts should be directed at increasing compliance to individual protocol elements.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Fidelidade a Diretrizes , Humanos , Estudos Prospectivos , Feminino , Masculino , Fidelidade a Diretrizes/estatística & dados numéricos , Pessoa de Meia-Idade , Idoso , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Pneumonectomia/efeitos adversos , Pneumonectomia/métodos , Tempo de Internação/estatística & dados numéricos , Protocolos Clínicos
18.
Am J Occup Ther ; 78(4)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38861552

RESUMO

IMPORTANCE: Veterans receiving inpatient psychiatric services with limitations in activities of daily living (ADLs) benefit from occupational therapy, yet disparities in access are unknown. OBJECTIVE: To investigate whether ADL limitations, an indicator of occupational therapy need, was associated with inpatient psychiatric occupational therapy utilization in the Veterans Health Administration (VHA) and whether this relationship differs by facility characteristics. DESIGN: Secondary analysis of VHA data. Modified Poisson regression modeled occupational therapy utilization as a function of ADL limitations, facility characteristics, and covariates. Interactions estimated whether the relationship between ADL limitations and occupational therapy utilization differed across facility characteristics. SETTING: VHA inpatient psychiatric setting. PARTICIPANTS: Veterans receiving VHA inpatient psychiatric care from 2015 to 2020 (N = 133,844). OUTCOMES AND MEASURES: Occupational therapy utilization. RESULTS: Veterans with ADL limitations were more likely to receive occupational therapy. Veterans receiving care in facilities with higher complexity and greater inpatient psychiatric care quality were more likely to receive occupational therapy. Additionally, Black veterans were less likely to receive occupational therapy relative to their White, non-Hispanic counterparts. Interactions indicated that the extent to which ADL limitations drove access to occupational therapy utilization was weaker within facilities with higher complexity and care quality. CONCLUSIONS AND RELEVANCE: Veterans with ADL limitations were more likely to access inpatient psychiatric occupational therapy, suggesting that such services are generally allocated to veterans in need. However, findings indicate disparities in access across patient-level (e.g., Black race) and facility-level (e.g., facility complexity) factors, informing efforts to eliminate barriers to accessing these valuable services. Plain-Language Summary: This is the first study, to our knowledge, to examine disparities in access to inpatient psychiatric occupational therapy in the Veterans Health Administration (VHA). The study findings show that access to inpatient psychiatric occupational therapy is partly driven by the needs of the patient. However, nonclinical factors, such as a patient's race and the characteristics of the facility at which they receive care (complexity, number of psychiatric beds available, and the quality of psychiatric care), are also important drivers of access. Identifying factors influencing access to these valuable services is the first step in developing strategies that reduce barriers to access for veterans in need.


Assuntos
Atividades Cotidianas , Acessibilidade aos Serviços de Saúde , Disparidades em Assistência à Saúde , Terapia Ocupacional , United States Department of Veterans Affairs , Humanos , Estados Unidos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Veteranos , Pacientes Internados , Transtornos Mentais/reabilitação , Idoso , Serviços de Saúde Mental/estatística & dados numéricos
19.
Ophthalmol Sci ; 4(5): 100519, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38881606

RESUMO

Clinical Relevance: Visual function impairment from diabetic retinopathy can have a considerable impact on patient's quality of life. Best-corrected visual acuity (BCVA) is most commonly used to assess visual function and guide clinical trials. However, BCVA is affected late in the disease process, is not affected in early disease, and does not capture some of the visual disturbances described by patients with diabetes. The goal of this report is to evaluate the relationship between diabetic retinal disease (DRD) and visual function parameters to determine which if any of them may be used in a future DRD staging system. Methods: The visual functions working group was 1 of 6 areas of DRD studied as part of the DRD staging system update, a project of the Mary Tyler Moore Vision Initiative. The working group identified 12 variables of possible interest, 7 of which were judged to have sufficient preliminary data to suggest an association with DR to warrant further review: microperimetry, static automated perimetry, electroretinogram (ERG) oscillatory potentials, flicker ERG, low luminance visual acuity (LLVA), contrast sensitivity (CS), and BCVA. The objective field analyzer (OFA) was added after subsequent in-person workshops. Results: Currently, the only visual function test available for immediate use is BCVA; the remaining tests are either promising (within 5 years) or have potential (>5 years) use. Besides BCVA, most visual function tests had a limited role in current clinical care; however, LLVA, CS, flicker ERG, and OFA demonstrated potential for screening and research purposes. Conclusions: Although current visual function tests are promising, future prospective studies involving patients with early and more advanced retinopathy are necessary to determine if these tests can be used clinically or as endpoints for clinical studies. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

20.
Sci Rep ; 14(1): 14514, 2024 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-38914624

RESUMO

The application of beneficial microorganisms for corals (BMC) decreases the bleaching susceptibility and mortality rate of corals. BMC selection is typically performed via molecular and biochemical assays, followed by genomic screening for BMC traits. Herein, we present a comprehensive in silico framework to explore a set of six putative BMC strains. We extracted high-quality DNA from coral samples collected from the Red Sea and performed PacBio sequencing. We identified BMC traits and mechanisms associated with each strain as well as proposed new traits and mechanisms, such as chemotaxis and the presence of phages and bioactive secondary metabolites. The presence of prophages in two of the six studied BMC strains suggests their possible distribution within beneficial bacteria. We also detected various secondary metabolites, such as terpenes, ectoines, lanthipeptides, and lasso peptides. These metabolites possess antimicrobial, antifungal, antiviral, anti-inflammatory, and antioxidant activities and play key roles in coral health by reducing the effects of heat stress, high salinity, reactive oxygen species, and radiation. Corals are currently facing unprecedented challenges, and our revised framework can help select more efficient BMC for use in studies on coral microbiome rehabilitation, coral resilience, and coral restoration.


Assuntos
Antozoários , Probióticos , Antozoários/genética , Antozoários/microbiologia , Antozoários/metabolismo , Animais , Oceano Índico , Genômica/métodos , Bactérias/genética , Microbiota
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