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1.
Health Qual Life Outcomes ; 22(1): 36, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38649987

ABSTRACT

CONTEXT: In France, 2300 adolescents and young adults (AYAs, 15-25 years old) are diagnosed with cancer each year. As soon as the disease is diagnosed, a number of physical, psychological and social needs may arise. The aim of this study is to develop a tool to measure unmet needs that will allow the specificities of AYAs to be understood while allowing health care staff to mobilise the necessary actors to resolve them. METHODS: We developed the Questionnaire nEEd Cancer AYAs (QUEEC-AYAs questionnaire), from two existing questionnaires: the Cancer Needs Questionnaire Young People and the Needs Assessment & Service Bridge. A main sample of 103 AYAs then received and completed the questionnaire in order to conduct an exploratory factor analysis. RESULTS: The final structure of the QUEEC-AYAs is composed of 7 dimensions and 48 items: information (8 items), cancer care team (6 items), Physical health (4 items), Emotional health (14 items), Sexual & reproductive health (6 items), Health behaviors & wellness (4 items), Daily life (6 items). The questionnaire has a good acceptability and all domains have a Cronbach's alphas value above 0.80. CONCLUSION: The QUEEC-AYAs is the first measure of the psychosocial needs of AYAs available in French. Its systematic use in health care services should improve the coordination of care required by AYAs during and after treatment. TRIAL REGISTRATION: This study was approved by the ethics committee of the Paoli-Calmettes Institute (IRB # IPC 2021-041, 2021 May 20).


Subject(s)
Needs Assessment , Neoplasms , Humans , Surveys and Questionnaires , Adolescent , Neoplasms/psychology , Neoplasms/therapy , Young Adult , Female , Male , France , Adult , Psychometrics , Reproducibility of Results , Health Services Needs and Demand , Quality of Life/psychology
2.
bioRxiv ; 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38586026

ABSTRACT

Molecular control of recovery after exercise in muscle is temporally dynamic. A time course of biopsies around resistance exercise (RE) combined with -omics is necessary to better comprehend the molecular contributions of skeletal muscle adaptation in humans. Vastus lateralis biopsies before and 30 minutes, 3-, 8-, and 24-hours after acute RE were collected. A time-point matched biopsy-only group was also included. RNA-sequencing defined the transcriptome while DNA methylomics and computational approaches complemented these data. The post-RE time course revealed: 1) DNA methylome responses at 30 minutes corresponded to upregulated genes at 3 hours, 2) a burst of translation- and transcription-initiation factor-coding transcripts occurred between 3 and 8 hours, 3) global gene expression peaked at 8 hours, 4) ribosome-related genes dominated the mRNA landscape between 8 and 24 hours, 5) methylation-regulated MYC was a highly influential transcription factor throughout the 24-hour recovery and played a primary role in ribosome-related mRNA levels between 8 and 24 hours. The influence of MYC in human muscle adaptation was strengthened by transcriptome information from acute MYC overexpression in mouse muscle. To test whether MYC was sufficient for hypertrophy, we generated a muscle fiber-specific doxycycline inducible model of pulsatile MYC induction. Periodic 48-hour pulses of MYC over 4 weeks resulted in higher muscle mass and fiber size in the soleus of adult female mice. Collectively, we present a temporally resolved resource for understanding molecular adaptations to RE in muscle and reveal MYC as a regulator of RE-induced mRNA levels and hypertrophy.

3.
Int J Surg ; 110(1): 238-252, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-37755384

ABSTRACT

BACKGROUND: Lymph node (LN) dissection is a common procedure for non-small cell lung cancer (NSCLC) to ascertain disease severity and treatment options. However, murine studies have indicated that excising tumor-draining LNs diminished immunotherapy effectiveness, though its applicability to clinical patients remains uncertain. Hence, the authors aim to illustrate the immunological implications of LN dissection by analyzing the impact of dissected LN (DLN) count on immunotherapy efficacy, and to propose a novel 'immunotherapy-driven' LN dissection strategy. MATERIALS AND METHODS: The authors conducted a retrospective analysis of NSCLC patients underwent anti-PD-1 immunotherapy for recurrence between 2018 and 2020, assessing outcomes based on DLN count stratification. RESULTS: A total of 144 patients were included, of whom 59 had a DLN count less than or equal to 16 (median, IQR: 11, 7-13); 66 had a DLN count greater than 16 (median, IQR: 23, 19-29). With a median follow-up time of 14.3 months (95% CI: 11.0-17.6), the overall median progression-free survival (PFS) was 7.9 (95% CI: 4.1-11.7) months, 11.7 (95% CI: 7.9-15.6) months in the combination therapy subgroup, and 4.8 (95% CI: 3.1-6.4) months in the immunotherapy alone subgroup, respectively. In multivariable Cox analysis, DLN count less than or equal to 16 is associated with an improved PFS in all cohorts [primary cohort: HR=0.26 (95% CI: 0.07-0.89), P =0.03]; [validation cohort: HR=0.46 (95% CI: 0.22-0.96), P =0.04]; [entire cohort: HR=0.53 (95% CI: 0.32-0.89), P =0.02]. The prognostic benefit of DLN count less than or equal to 16 was more significant in immunotherapy alone, no adjuvant treatment, pN1, female, and squamous carcinoma subgroups. A higher level of CD8+ central memory T cell (Tcm) within LNs was associated with improved PFS (HR: 0.235, 95% CI: 0.065-0.845, P =0.027). CONCLUSIONS: An elevated DLN count (cutoff: 16) was associated with poorer immunotherapy efficacy in recurrent NSCLC, especially pronounced in the immunotherapy alone subgroup. CD8+Tcm proportions in LNs may also impact immunotherapy efficacy. Therefore, for patients planned for adjuvant immunotherapy, a precise rather than expanded lymphadenectomy strategy to preserve immune-depending LNs is recommended.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Female , Animals , Mice , Carcinoma, Non-Small-Cell Lung/surgery , Lung Neoplasms/surgery , Retrospective Studies , Neoplasm Recurrence, Local/surgery , Lymph Node Excision , Immunotherapy
4.
JTCVS Tech ; 22: 265-272, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38152171

ABSTRACT

Objectives: Transbronchial microwave ablation of lung nodules using electromagnetic navigation bronchoscopy is an emerging local therapy for lung oligometastases and multifocal lung cancers as part of a lung-preserving strategy. Concomitant ablation of multiple lung nodules in a single operating session may provide a one-stop solution. Methods: Between April 2019 and April 2023, 25 patients had 2 or more lung nodules ablated concomitantly in our hybrid operating room. Nodules were proven or highly suspicious of malignancies or metastases. Feasibility and safety were retrospectively reviewed. Results: A total of 56 nodules in 25 patients received concomitant multi-nodular ablation. The mean age of patients was 60 years, and the reasons for the lung-preserving strategy were multifocal lung cancers (80%) and lung oligometastases (20%). Among those with multifocal disease, 65% had previous major lung resection for lung cancer. Two to 4 nodules were ablated in each session. The mean nodule size was 9.9 mm (range, 5-20 mm), and the mean minimal margin was 5.9 mm. When comparing concomitant nodule ablation with the 103 single-nodule ablations performed in our institute, a mean of 86 minutes of operative time and 131 minutes of anesthetic time were saved. There were no increased complications despite overlapping ablation zones, and the mean hospital stay was 1.23 days. The rate of pneumothorax was 8%, and that of pleural effusion, pain, and fever was 4% respectively. Conclusions: Concomitant transbronchial microwave ablation of multiple lung nodules is feasible, safe, and associated with reduction in overall anesthetic and operative time. It is an important armamentarium in the contemporary lung-preserving strategy for battling multifocal lung cancers or lung oligometastases.

6.
Ann Emerg Med ; 2023 Sep 19.
Article in English | MEDLINE | ID: mdl-37725021

ABSTRACT

STUDY OBJECTIVE: Button battery ingestion can cause alkaline esophageal injury. There is interest in first-aid household products to neutralize the injury. The objective was to investigate which household products are effective at reducing button battery injury. METHODS: Two cadaveric porcine experiments were performed. Experiment 1 utilized esophageal mucosal segments. A button battery (3VCR2032) was placed onto the mucosa, and substances (saline control, honey, jam, orange juice, yogurt, milk, and cola) were applied every 10 minutes for 6 applications. Tissue pH was measured every 10 minutes, and macroscopic ulceration size was assessed at 120 minutes. Experiment 2 used an intact esophageal model with a battery inserted into the lumen and jam, honey, and saline irrigation as per experiment 1. Tissue pH, macroscopic and histopathology changes were evaluated at 60, 90 and 120 minutes. RESULTS: In experiment 1, only honey and jam had a lower mean tissue pH at 120 minutes (8.0 [standard deviation [SD] 0.9, n=12] and 7.1 [SD 1.7, n=12], respectively) compared to saline solution 11.9 (SD 0.6, n=6, P<.0001). Both honey (0.24 cm2, SD 0.17) and jam (0.37 cm2, SD 0.40) had smaller mean areas of ulceration compared to saline solution (3.90 cm2, SD 1.03, P<.0001). In experiment 2, honey and jam had significantly lower mean tissue pH at all timepoints compared to saline solution. Histologic changes were evident at 60 minutes in the saline group, whereas honey and jam exhibited no or minimal changes until 120 minutes. CONCLUSIONS: Honey and jam were able to neutralize injury caused by a button battery resulting in a smaller area of ulceration. Jam should be further explored as a possible first-aid option as an alternative to honey in suspected button battery ingestion prior to definitive management.

7.
Article in English | MEDLINE | ID: mdl-37747275

ABSTRACT

BACKGROUND: Image-guided thermal ablation is a minimally invasive local therapy for lung malignancies. NAVABLATE characterized the safety and performance of transbronchial microwave ablation (MWA) in the lung. METHODS: The prospective, single-arm, 2-center NAVABLATE study (NCT03569111) evaluated transbronchial MWA in patients with histologically confirmed lung malignancies ≤30 mm in maximum diameter who were not candidates for, or who declined, both surgery and stereotactic body radiation therapy. Ablation of 1 nodule was allowed per subject. The nodule was reached with electromagnetic navigation bronchoscopy. Cone-beam computed tomography was used to verify the ablation catheter position and to evaluate the ablation zone postprocedure. The primary end point was composite adverse events related to the transbronchial MWA device through 1-month follow-up. Secondary end points included technical success (nodule reached and ablated according to the study protocol) and technique efficacy (satisfactory ablation based on 1-month follow-up imaging). RESULTS: Thirty subjects (30 nodules; 66.7% primary lung, 33.3% oligometastatic) were enrolled from February 2019 to September 2020. The pre-procedure median nodule size was 12.5 mm (range 5 to 27 mm). Procedure-day technical success was 100% (30/30), with a mean ablative margin of 9.9±2.7 mm. One-month imaging showed 100% (30/30) technique efficacy. The composite adverse event rate related to the transbronchial MWA device through 1-month follow-up was 3.3% (1 subject, mild hemoptysis). No deaths or pneumothoraces occurred. Four subjects (13.3%) experienced grade 3 complications; none had grade 4 or 5. CONCLUSION: Transbronchial microwave ablation is an alternative treatment modality for malignant lung nodules ≤30 mm. There were no deaths or pneumothorax. In all, 13.3% of patients developed grade 3 or above complications.

8.
Hepatobiliary Surg Nutr ; 12(4): 534-544, 2023 Aug 01.
Article in English | MEDLINE | ID: mdl-37601001

ABSTRACT

Background: Existing reporting guidelines pay insufficient attention to the detail and comprehensiveness reporting of surgical technique. The Surgical techniqUe rePorting chEcklist and standaRds (SUPER) aims to address this gap by defining reporting standards for surgical technique. The SUPER guideline intends to apply to articles that encompass surgical technique in any study design, surgical discipline, and stage of surgical innovation. Methods: Following the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) Network approach, 16 surgeons, journal editors, and methodologists reviewed existing reporting guidelines relating to surgical technique, reviewed papers from 15 top journals, and brainstormed to draft initial items for the SUPER. The initial items were revised through a three-round Delphi survey from 21 multidisciplinary Delphi panel experts from 13 countries and regions. The final SUPER items were formed after an online consensus meeting to resolve disagreements and a three-round wording refinement by all 16 SUPER working group members and five SUPER consultants. Results: The SUPER reporting guideline includes 22 items that are considered essential for good and informative surgical technique reporting. The items are divided into six sections: background, rationale, and objectives (items 1 to 5); preoperative preparations and requirements (items 6 to 9); surgical technique details (items 10 to 15); postoperative considerations and tasks (items 16 to 19); summary and prospect (items 20 and 21); and other information (item 22). Conclusions: The SUPER reporting guideline has the potential to guide detailed, comprehensive, and transparent surgical technique reporting for surgeons. It may also assist journal editors, peer reviewers, systematic reviewers, and guideline developers in the evaluation of surgical technique papers and help practitioners to better understand and reproduce surgical technique. Trial Registration: https://www.equator-network.org/library/reporting-guidelines-under-development/reporting-guidelines-under-development-for-other-study-designs/#SUPER.

9.
Nat Cell Biol ; 25(7): 1017-1032, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37414849

ABSTRACT

Chromatin is dynamically reorganized when DNA replication forks are challenged. However, the process of epigenetic reorganization and its implication for fork stability is poorly understood. Here we discover a checkpoint-regulated cascade of chromatin signalling that activates the histone methyltransferase EHMT2/G9a to catalyse heterochromatin assembly at stressed replication forks. Using biochemical and single molecule chromatin fibre approaches, we show that G9a together with SUV39h1 induces chromatin compaction by accumulating the repressive modifications, H3K9me1/me2/me3, in the vicinity of stressed replication forks. This closed conformation is also favoured by the G9a-dependent exclusion of the H3K9-demethylase JMJD1A/KDM3A, which facilitates heterochromatin disassembly upon fork restart. Untimely heterochromatin disassembly from stressed forks by KDM3A enables PRIMPOL access, triggering single-stranded DNA gap formation and sensitizing cells towards chemotherapeutic drugs. These findings may help in explaining chemotherapy resistance and poor prognosis observed in patients with cancer displaying elevated levels of G9a/H3K9me3.


Subject(s)
Heterochromatin , Histones , Humans , Histones/genetics , Histones/metabolism , Heterochromatin/genetics , Chromatin/genetics , Chromatin Assembly and Disassembly , DNA Replication , Histocompatibility Antigens , Histone-Lysine N-Methyltransferase/genetics , Histone-Lysine N-Methyltransferase/metabolism , Jumonji Domain-Containing Histone Demethylases/genetics
10.
Gland Surg ; 12(6): 749-766, 2023 Jun 30.
Article in English | MEDLINE | ID: mdl-37441012

ABSTRACT

Background: Surgical technique plays an essential role in achieving good health outcomes. However, the quality of surgical technique reporting remains heterogeneous. Reporting checklists could help authors to describe the surgical technique more transparently and effectively, as well as to assist reviewers and editors evaluate it more informatively, and promote readers to better understand the technique. We previously developed SUPER (surgical technique reporting checklist and standards) to assist authors in reporting their research that contains surgical technique more transparently. However, further explanation and elaboration of each item are needed for better understanding and reporting practice. Methods: We searched surgical literature in PubMed, Google Scholar and journal websites published up to January 2023 to find multidiscipline examples in various article types for each SUPER item. Results: We explain the 22 items of the SUPER and provide rationales item by item alongside. We provide 69 examples from 53 literature that present optimal reporting of the 22 items. Article types of examples include pure surgical technique, and case reports, observational studies and clinical trials that contain surgical technique. Examples are multidisciplinary, including general surgery, orthopaedical surgery, cardiac surgery, thoracic surgery, gastrointestinal surgery, neurological surgery, oncogenic surgery, and emergency surgery etc. Conclusions: Along with SUPER article, this explanation and elaboration file can promote deeper understanding on the SUPER items. We hope that the article could further guide surgeons and researchers in reporting, and assist editors and peer reviewers in reviewing manuscripts related to surgical technique.

11.
AME Case Rep ; 7: 13, 2023.
Article in English | MEDLINE | ID: mdl-37122960

ABSTRACT

Background: Transbronchial ablation of lung nodules is gaining popularity as part of lung-preserving strategy for patients with multifocal lung cancers or multiple lung oligometastases. Accuracy in placement of ablation catheter is of utmost importance in order to achieve adequate ablation margin. However, older systems are not precise enough for confident placement of ablation catheter and often require multiple cone-beam CT (CBCT) to confirm and readjust its position. The following case is the first microwave lung ablation utilizing the novel IllumisiteTM platform (Medtronic, Minneapolis, MN, USA) in the hybrid operating room (HOR), with enhanced accuracy and workflow. Case Description: A 66-year-old lady had multiple resected adenocarcinomas in bilateral lungs. Upon CT monitoring a right middle lobe (RML) ground glass opacity with solid centre was found to be suspicious due to increasing size and density. Transbronchial electromagnetic navigation bronchoscopy (ENB) microwave ablation of the lesion was performed as part of lung-conserving strategy. After initial navigation, the adjusted nodule position provided by the IllumisiteTM platform after correcting the CT-to-body divergence prompted operators to renavigate and readjust the position of the locatable guide (LG) swiftly to gain accurate access to the nodule, which was confirmed by CBCT. Positional data at the tip of extended working channel (EWC) also allowed precise placement of needle for subsequent ablation. Conclusions: IllumisiteTM is a novel electromagnetic navigational platform that corrects for CT-to-body divergence and ensures continuous locational information by an additional positional coil in the tip of EWC. This precision is especially important for the placement of ablation catheter, as slight deviation would lead to insufficient ablation margin and future recurrence. Workflow is improved by reducing the number of CBCT required for instrument position adjustment.

12.
Trop Med Health ; 51(1): 31, 2023 May 25.
Article in English | MEDLINE | ID: mdl-37226211

ABSTRACT

BACKGROUND: Dengue remains a major public health problem in the Philippines, particularly in urban areas of the National Capital Region. Thematic mapping using geographic information systems complemented by spatial analysis such as cluster analysis and hot spot detection can provide useful information to guide preventive measures and control strategies against dengue. Hence, this study was aimed to describe the spatiotemporal distribution of dengue incidence and identify dengue hot spots by barangay using reported cases from Quezon City, the Philippines from 2010 to 2017. METHODS: Reported dengue case data at barangay level from January 1, 2010 to December 31, 2017 were obtained from the Quezon City Epidemiology and Surveillance Unit. The annual incidence rate of dengue from 2010 to 2017, expressed as the total number of dengue cases per 10,000 population in each year, was calculated for each barangay. Thematic mapping, global cluster analysis, and hot spot analysis were performed using ArcGIS 10.3.1. RESULTS: The number of reported dengue cases and their spatial distribution varied highly between years. Local clusters were evident during the study period. Eighteen barangays were identified as hot spots. CONCLUSIONS: Considering the spatial heterogeneity and instability of hot spots in Quezon City across years, efforts towards the containment of dengue can be made more targeted, and efficient with the application of hot spot analysis in routine surveillance. This may be useful not only for the control of dengue but also for other diseases, and for public health planning, monitoring, and evaluation.

13.
Contemp Clin Trials Commun ; 33: 101120, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37026030

ABSTRACT

Physical activity has been shown to have many benefits, including reducing cancer-related fatigue (CRF) and improving psychological and physical recovery from breast cancer. Some authors have shown the benefits of aquatic practice, while others have detailed the benefits of group and supervised practice. We hypothesize that an innovative sports coaching proposal could allow a significant adherence of patients and contribute to their health improvement. The main objective is to study the feasibility of an adapted water polo programme (aqua polo) for women after breast cancer. Secondarily we will analyse the effect of such a practice on patients' recovery and study the relationship between coaches and participants. The use of mixed methods will allow us to question the underlying processes precisely. This is a prospective, non-randomized, monocentric study with a sample of 24 breast cancer patients after treatment. The intervention is a 20 week programme (1 session per week) of aqua polo in a swim club facility, supervised by professional water-polo coaches. The variables measured are patient participation, quality of life (QLQ BR23), CRF (R-PFS) and post-traumatic growth (PTG-I) as well as different variables to observe physical capacity (strength with dynamometer, step-test and arm amplitude). The quality of the coach-patient relationship will be evaluated (CART-Q) to explore its dynamics. Participatory observations and interviews will be carried out to report on the interactions between the coach and the participants during the sessions. Registration number and name of trial registry: No. EudraCT or ID-RCB: 2019-A03003-54 and NCT: NCT04235946.

14.
Trop Med Health ; 51(1): 19, 2023 Mar 30.
Article in English | MEDLINE | ID: mdl-36998001

ABSTRACT

BACKGROUND: As a component of health promoting school, a school curriculum for health education was considered a fundamental. This survey aimed to identify the components of health-related topics and in which subjects were they taught. METHODS: Four topics were chosen: (i) hygiene, (ii) mental health, (iii) nutrition-oral Health, and (iv) environmental education related to global warming in Education for Sustainable Development (ESD). Before gathering the curricula from partner countries, school health specialists were gathered to discuss the appropriate components of a curriculum that required evaluation. The survey sheet was distributed to and answered by our partner in each country. RESULTS: About hygiene, individual practices or items that improve health-related were widely covered. However, items that imparted health-related education from an environmental perspective were not widely covered. About mental health, two types of country groups were identified. The first group included countries that taught mental health topics mainly as part of morals or religion; the second group included countries that imparted mental health topics mainly as part of health. The first group focused mainly on communication skills or coping methods. The second group focused not only on communication and coping skill but also on basic knowledge of mental health. About nutrition-oral education, three types of country groups were identified. One group imparted nutrition-oral education mainly in terms of health or nutrition. Another group imparted this topic mainly in terms of morals, home economics, and social science. The third group was the intermediate group. About ESD, a solid structure for this topic was not identified in any country. Many items were taught as part of science, while some were taught as part of social studies. Climate change was the most commonly taught item across all countries. The items related to environment were relatively limited compared to those related to natural disasters. CONCLUSIONS: Overall, two different approaches were identified: the cultural-based approach, which promotes healthy behaviors as moral codes or community-friendly behaviors and the science-based approach, which promotes children's health through scientific perspectives. Policymakers should initially  consider the findings of this study while making decisions on which approach should be taken.

15.
Ann Cardiothorac Surg ; 12(1): 46-48, 2023 Jan 31.
Article in English | MEDLINE | ID: mdl-36793980
16.
Cancers (Basel) ; 15(4)2023 Feb 08.
Article in English | MEDLINE | ID: mdl-36831411

ABSTRACT

The demand for parenchyma-sparing local therapies for lung cancer is rising owing to an increasing incidence of multifocal lung cancers and patients who are unfit for surgery. With the latest evidence of the efficacy of lung cancer screening, more premalignant or early-stage lung cancers are being discovered and the paradigm has shifted from treatment to prevention. Transbronchial therapy is an important armamentarium in the local treatment of lung cancers, with microwave ablation being the most promising based on early to midterm results. Adjuncts to improve transbronchial ablation efficiency and accuracy include mobile C-arm platforms, software to correct for the CT-to-body divergence, metal-containing nanoparticles, and robotic bronchoscopy. Other forms of energy including steam vapor therapy and pulse electric field are under intensive investigation.

17.
Front Microbiol ; 14: 1015666, 2023.
Article in English | MEDLINE | ID: mdl-36846764

ABSTRACT

Research on the role of gut microbiota in behavior has grown dramatically. The probiotic L. reuteri can alter social and stress-related behaviors - yet, the underlying mechanisms remain largely unknown. Although traditional laboratory rodents provide a foundation for examining the role of L. reuteri on the gut-brain axis, they do not naturally display a wide variety of social behaviors. Using the highly-social, monogamous prairie vole (Microtus ochrogaster), we examined the effects of L. reuteri administration on behaviors, neurochemical marker expression, and gut-microbiome composition. Females, but not males, treated with live L. reuteri displayed lower levels of social affiliation compared to those treated with heat-killed L. reuteri. Overall, females displayed a lower level of anxiety-like behaviors than males. Live L. reuteri-treated females had lower expression of corticotrophin releasing factor (CRF) and CRF type-2-receptor in the nucleus accumbens, and lower vasopressin 1a-receptor in the paraventricular nucleus of the hypothalamus (PVN), but increased CRF in the PVN. There were both baseline sex differences and sex-by-treatment differences in gut microbiome composition. Live L. reuteri increased the abundance of several taxa, including Enterobacteriaceae, Lachnospiraceae NK4A136, and Treponema. Interestingly, heat-killed L. reuteri increased abundance of the beneficial taxa Bifidobacteriaceae and Blautia. There were significant correlations between changes in microbiota, brain neurochemical markers, and behaviors. Our data indicate that L. reuteri impacts gut microbiota, gut-brain axis and behaviors in a sex-specific manner in socially-monogamous prairie voles. This demonstrates the utility of the prairie vole model for further examining causal impacts of microbiome on brain and behavior.

18.
Hum Mol Genet ; 32(10): 1634-1646, 2023 05 05.
Article in English | MEDLINE | ID: mdl-36621967

ABSTRACT

Autism spectrum disorder (ASD) affects 1 in 44 children. Chromatin regulatory proteins are overrepresented among genes that contain high risk variants in ASD. Disruption of the chromatin environment leads to widespread dysregulation of gene expression, which is traditionally thought of as a mechanism of disease pathogenesis associated with ASD. Alternatively, alterations in chromatin dynamics could also lead to dysregulation of alternative splicing, which is understudied as a mechanism of ASD pathogenesis. The anticonvulsant valproic acid (VPA) is a well-known environmental risk factor for ASD that acts as a class I histone deacetylase inhibitor. However, the precise molecular mechanisms underlying defects in human neuronal development associated with exposure to VPA are understudied. To dissect how VPA exposure and subsequent chromatin hyperacetylation influence molecular signatures involved in ASD pathogenesis, we conducted RNA sequencing (RNA-seq) in human cortical neurons that were treated with VPA. We observed that differentially expressed genes (DEGs) were enriched for mRNA splicing, mRNA processing, histone modification and metabolism related gene sets. Furthermore, we observed widespread increases in the number and the type of alternative splicing events. Analysis of differential transcript usage (DTU) showed that exposure to VPA induces extensive alterations in transcript isoform usage across neurodevelopmentally important genes. Finally, we find that DEGs and genes that display DTU overlap with known ASD-risk genes. Altogether, these findings suggest that, in addition to differential gene expression, changes in alternative splicing correlated with alterations in the chromatin environment could act as an additional mechanism of disease in ASD.


Subject(s)
Autism Spectrum Disorder , Prenatal Exposure Delayed Effects , Child , Humans , Animals , Female , Autism Spectrum Disorder/etiology , Chromatin/genetics , Alternative Splicing/genetics , Valproic Acid/adverse effects , RNA, Messenger/metabolism , Disease Models, Animal
19.
Pharmacol Ther ; 241: 108333, 2023 01.
Article in English | MEDLINE | ID: mdl-36528259

ABSTRACT

Although in the last few decades we have witnessed the rapid development of treatments for non-small cell lung cancer (NSCLC), it still remains the leading cause of cancer-related death. Increasing efforts have been devoted to exploring potential biomarkers and molecular targets for NSCLC. Foxp3, a transcription factor that was discovered as a master regulator of regulatory T cells (Tregs), has been found to express abnormally in tumoral cells including lung cancer cells. In recent years, increasing evidence have surfaced, revealing the carcinogenic effect of FOXP3 in lung cancer. In this review, we analyzed and summarized the function of FOXP3, its regulation and therapeutic potentials in NSCLC, with a hope to facilitate the development of novel treatments for NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/metabolism , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Forkhead Transcription Factors , Lung/metabolism , T-Lymphocytes, Regulatory
20.
J Clin Epidemiol ; 155: 1-12, 2023 03.
Article in English | MEDLINE | ID: mdl-36574532

ABSTRACT

OBJECTIVES: To identify reporting guidelines related to surgical technique and propose recommendations for areas that require improvement. STUDY DESIGN AND SETTING: A protocol-guided scoping review was conducted. A literature search of MEDLINE, the EQUATOR Network Library, Google Scholar, and Networked Digital Library of Theses and Dissertations was conducted to identify surgical technique reporting guidelines published up to December 31, 2021. RESULTS: We finally included 55 surgical technique reporting guidelines, vascular surgery (n = 18, 32.7%) was the most common among the clinical specialties covered. The included guidelines generally showed a low degree of international and multidisciplinary cooperation. Few guidelines provided a detailed development process (n = 14, 25.5%), conducted a systematic literature review (n = 13, 23.6%), used the Delphi method (n = 4, 7.3%), or described post-publication strategy (n = 6, 10.9%). The vast majority guidelines focused on the reporting of intraoperative period (n = 50, 90.9%). However, of the guidelines requiring detailed descriptions of surgical technique methodology (n = 43, 78.2%), most failed to provide guidance on what constitutes an adequate description. CONCLUSION: Our study demonstrates significant deficiencies in the development methodology and practicality of reporting guidelines for surgical technique. A standardized reporting guideline that is developed rigorously and focuses on details of surgical technique may serve as a necessary impetus for change.

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