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1.
Respirology ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38960450

RESUMO

Eligibility criteria for lung cancer screening increasingly need to consider family history of lung cancer, as well as age and smoking status. Lung cancer screening will reveal a multitude of incidental findings, of variable clinical significance, and with a need for clear pathways of management. Pulmonary nodule sampling is enhanced by intra-procedural imaging and cutting-edge robotic technology. Systematic thoracic lymph node sampling has implications for treatment efficacy. Bronchoscopic ablative techniques are feasible for peripheral lung cancers. Bronchoscopic sampling continues to have a high yield for lung cancer molecular characterization. Immunotherapy indications have expanded to include early stage and resectable lung cancer.

2.
Sci Rep ; 14(1): 14724, 2024 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956070

RESUMO

Across vertebrates, adaptive behaviors, like feeding and avoiding predators, are linked to lateralized brain function. The presence of the behavioral manifestations of these biases are associated with increased task success. Additionally, when an individual's direction of bias aligns with the majority of the population, it is linked to social advantages. However, it remains unclear if behavioral biases in humans correlate with the same advantages. This large-scale study (N = 313-1661, analyses dependent) examines whether the strength and alignment of behavioral biases associate with cognitive and social benefits respectively in humans. To remain aligned with the animal literature, we evaluate motor-sensory biases linked to motor-sequencing and emotion detection to assess lateralization. Results reveal that moderate hand lateralization is positively associated with task success and task success is, in turn, associated with language fluency, possibly representing a cascade effect. Additionally, like other vertebrates, the majority of our human sample possess a 'standard' laterality profile (right hand bias, left visual bias). A 'reversed' profile is rare by comparison, and associates higher self-reported social difficulties and increased rate of autism and/or attention deficit hyperactivity disorder. We highlight the importance of employing a comparative theoretical framing to illuminate how and why different laterization profiles associate with diverging social and cognitive phenotypes.


Assuntos
Cognição , Lateralidade Funcional , Humanos , Cognição/fisiologia , Masculino , Feminino , Lateralidade Funcional/fisiologia , Adulto , Adulto Jovem , Adolescente , Habilidades Sociais , Pessoa de Meia-Idade , Emoções/fisiologia
3.
Arch Sex Behav ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38914863

RESUMO

Parental communication about sex is an important aspect of sexual socialization. However, research has primarily focused on sexual communication's presence, frequency, or topics, with less research on the specific messages parents communicate. Further, few studies have differentiated between communication received before and after youth initiated sex. Therefore, in this paper, we coded open-ended survey responses to explore the sex-related messages young adults report receiving from their caregiver(s) before they began engaging in sex. As part of a larger study, 381 U.S. young adults (Mage = 21.0 years, SD = 2.0) completed an online survey and responded to an open-ended question about messages their caregiver(s) communicated before they began engaging in sex. Participants identified as cisgender women (62.2%), cisgender men (12.1%), and gender diverse (25.7%), and were primarily lesbian, gay, bisexual, queer, questioning, or otherwise non-heterosexual (LGBQ+; 70.6%) young adults. Through thematic analysis, we identified six themes for caregivers' sex-related messages: sex-restrictive, safety and consequences, no, negative, sex-positive, and informational messages. In addition, we found that messages varied by young adults' gender identity and sexual orientation. Our findings suggest that young adults may not receive proper education about healthy sexual relationships and demonstrate the need for interventions with caregivers, as well as sexual health resources for adolescents and young adults, particularly LGBTQ+ youth.

5.
Mil Med ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38861401

RESUMO

INTRODUCTION: Massage therapy is an evidence-based approach for pain management. Information regarding its utilization in the Military Health System (MHS) is lacking. The goal of this study is to evaluate massage therapy utilization patterns across the MHS to include who receives (patient characteristics and diagnoses) and provides (e.g., massage therapists) massage therapy and where (e.g., clinic type). MATERIALS AND METHODS: Medical record data of adult TRICARE Prime enrollees receiving outpatient massage therapy (Current Procedural Terminology codes: 97124 and 97140) from June 1, 2021, to May 31, 2023, were extracted from the MHS Data Repository. After identifying the index massage therapy visit, records for 6 months pre- and post-index were included. Descriptive statistics described massage therapy utilization patterns overall. Bivariate analysis compared patients who received massage therapy from massage therapists versus nonmassage therapist clinicians. RESULTS: Of patients who received massage therapy (n = 179,215), the median number of visits was 2 (interquartile range 1 to 4), the median age was 32 years (interquartile range 25 to 40), they were mostly assigned male (72%), White (53%), Senior Enlisted (51%), with a musculoskeletal diagnosis (90%), and recent non-steroidal anti-inflammatory drug (NSAID) prescription (58%). Massage therapy was primarily delivered by physical therapists (49%) in physical therapy clinics (74%). Massage therapists provided 0.2% of massage therapy. Patients who received massage therapy from massage therapists versus nonmassage therapists significantly varied across several patient and care characteristics. CONCLUSIONS: While massage therapy codes are documented frequently, massage therapists do not commonly provide massage therapy relative to nonmassage therapist providers. Access to massage therapists may be stymied by both lack of massage therapists and need for tertiary pain management referrals to access massage therapist-delivered care. Future research will leverage a health equity framework to (1) evaluate accessibility to massage therapy provided by massage therapists and (2) evaluate real-world evidence of massage therapy effectiveness.

6.
Methods Cell Biol ; 188: 153-169, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38880522

RESUMO

Pancreatic cancer remains an unmet medical need. Late diagnosis and the lack of efficient treatment significantly impact the prognosis of patients suffering from pancreatic cancer. Improving patient outcomes requires a deeper comprehension of the tumor ecosystem. To achieve this, a thorough exploration of the tumor microenvironment using pre-clinical models that accurately replicate human disease is imperative, particularly in understanding the dynamics of immune cell subsets. Surprisingly, the impact of model variations on the composition of the tumor microenvironment has been largely neglected. In this study, we introduce an orthotopic model of pancreatic ductal adenocarcinoma and a spontaneous model of insulinoma. Our findings reveal striking differences in the innate lymphoid cell infiltrate, highlighting the importance of considering model-specific influences when investigating the tumor microenvironment.


Assuntos
Carcinoma Ductal Pancreático , Modelos Animais de Doenças , Imunidade Inata , Linfócitos , Neoplasias Pancreáticas , Microambiente Tumoral , Animais , Camundongos , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/imunologia , Carcinoma Ductal Pancreático/imunologia , Carcinoma Ductal Pancreático/patologia , Microambiente Tumoral/imunologia , Linfócitos/imunologia , Humanos , Insulinoma/patologia , Insulinoma/imunologia , Linhagem Celular Tumoral , Camundongos Endogâmicos C57BL
7.
Cancers (Basel) ; 16(11)2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38893236

RESUMO

Risk-stratified breast screening has been proposed as a strategy to overcome the limitations of age-based screening. A prospective cohort study was undertaken within the PERSPECTIVE I&I project, which will generate the first Canadian evidence on multifactorial breast cancer risk assessment in the population setting to inform the implementation of risk-stratified screening. Recruited females aged 40-69 unaffected by breast cancer, with a previous mammogram, underwent multifactorial breast cancer risk assessment. The adoption of multifactorial risk assessment, the effectiveness of methods for collecting risk factor information and the costs of risk assessment were examined. Associations between participant characteristics and study sites, as well as data collection methods, were assessed using logistic regression; all p-values are two-sided. Of the 4246 participants recruited, 88.4% completed a risk assessment, with 79.8%, 15.7% and 4.4% estimated at average, higher than average and high risk, respectively. The total per-participant cost for risk assessment was CAD 315. Participants who chose to provide risk factor information on paper/telephone (27.2%) vs. online were more likely to be older (p = 0.021), not born in Canada (p = 0.043), visible minorities (p = 0.01) and have a lower attained education (p < 0.0001) and perceived fair/poor health (p < 0.001). The 34.4% of participants requiring risk factor verification for missing/unusual values were more likely to be visible minorities (p = 0.009) and have a lower attained education (p ≤ 0.006). This study demonstrates the feasibility of risk assessment for risk-stratified screening at the population level. Implementation should incorporate an equity lens to ensure cancer-screening disparities are not widened.

8.
J Sports Sci ; : 1-10, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38899730

RESUMO

This study examined the criterion validity of an ecological momentary assessment (EMA)-reported physical activity and sedentary time compared with accelerometry in shift workers and non-shift workers. Australian workers (n = 102) received prompts through a mobile EMA app and wore the Actigraph accelerometer on the right hip for 7-10 days. Participants received five EMA prompts per day at 3-hour intervals on their mobile phones. EMA prompts sent to shift workers (SW-T) were tailored according to their work schedule. Non-shift workers (NSW-S) received prompts at standardised times. To assess criterion validity, the association of EMA-reported activities and the Actigraph accelerometer activity counts and number of steps were used. Participants were 36 ± 11 years and 58% were female. On occasions where participants reported physical activity, acceleration counts per minute (CPM) and steps were significantly higher (ß = 1184 CPM, CI 95%: 1034, 1334; ß = 20.9 steps, CI 95%: 18.2, 23.6) than each of the other EMA activities. Acceleration counts and steps were lower when sitting was reported than when no sitting was reported by EMA. Our study showed that EMA-reported physical activity and sedentary time was significantly associated with accelerometer-derived data. Therefore, EMA can be considered to assess shift workers' movement-related behaviours with accelerometers to provide rich contextual data.

9.
Urol Case Rep ; 54: 102710, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38827529

RESUMO

We present the case of a patient with X-Linked Hypophosphatemia (XLH) and an inflammatory myofibroblastic tumor (IMT) of the bladder which prompted further investigation into the possible relationship between XLH and IMT i.e. a case of Occam's Razor or Hickam's Dictum?

10.
Dis Colon Rectum ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38830267

RESUMO

BACKGROUND: Medically refractory ulcerative colitis (UC) necessitates surgical intervention, with total abdominal colectomy with end ileostomy being a definitive treatment. The comparison between single-port and multi-port laparoscopic surgery outcomes remains underexplored. OBJECTIVE: To compare the surgical outcomes of single-port versus multi-port laparoscopic surgery in patients undergoing total abdominal colectomy with end ileostomy for medically refractory UC. DESIGN: A retrospective analysis comparing single-port to multi-port surgery in UC patients from 2010 to 2020. Patients were propensity score-matched 3:1 (multi-port to single-port) on baseline characteristics. SETTINGS: Single center academic hospital. MAIN OUTCOME MEASURES: Binary outcomes were compared using a multivariable logistic regression model, and a subset analysis was conducted for postoperative stump leak based on stump implantation during surgery. These metrics were compared between the single-port and multi-port groups to assess the differences in surgical outcomes. RESULTS: The multi-port and single-port groups included 642 and 114 patients, respectively. Matched cohort included 342 multi-ports and 114 single-ports. We observed a statistically significant difference in mean operation time, with the single-port procedure taking 43 minutes less than the multi-port laparoscopy. There were no significant differences between the two groups in postoperative stump leaks, postoperative ileus, stoma site complications, postoperative readmission within 30 days, postoperative reoperation within 30 days, and subsequent IPAA surgery. In the subset analysis, stump implantation was associated with a higher risk of stump leak in the multiport group. The single-port group had a shorter hospital stay. LIMITATIONS: Retrospective nature, being conducted at a single center. CONCLUSION: Single-incision laparoscopic total abdominal colectomy in the treatment of mucosal ulcerative colitis is a safe, effective, and efficient approach. In our cohort, as compared to multi-port approach, single incision laparoscopy has shown shorter operation times and better overall length of stay. Taking into account less invasive approach, decreased abdominal trauma, and faster recovery, single-port surgery is a viable alternative to multi-port surgery. See Video Abstract.

11.
Antimicrob Agents Chemother ; : e0033424, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38864613

RESUMO

Islatravir (ISL) is a deoxyadenosine analog that inhibits HIV-1 reverse transcription by multiple mechanisms. Lenacapavir (LEN) is a novel capsid inhibitor that inhibits HIV-1 at multiple stages throughout the viral life cycle. ISL and LEN are being investigated as once-weekly combination oral therapy for the treatment of HIV-1. Here, we characterized ISL and LEN in vitro to assess combinatorial antiviral activity, cytotoxicity, and the potential for interactions between the two compounds. Bliss analysis revealed ISL with LEN demonstrated additive inhibition of HIV-1 replication, with no evidence of antagonism across the range of concentrations tested. ISL exhibited potent antiviral activity against variants encoding known LEN resistance-associated mutations (RAMs) with or without the presence of M184V, an ISL RAM in reverse transcriptase (RT) . Static resistance selection experiments were conducted with ISL and LEN alone and in combination, initiating with either wild-type virus or virus containing the M184I RAM in RT to further assess their barrier to the emergence of resistance. The combination of ISL with LEN more effectively suppressed viral breakthrough at lower multiples of the compounds' IC50 (half-maximal inhibitory concentration) values and fewer mutations emerged with the combination compared to either compound on its own. The known pathways for development of resistance with ISL and LEN were not altered, and no novel single mutations emerged that substantially reduced susceptibility to either compound. The lack of antagonism and cross-resistance between ISL and LEN support the ongoing evaluation of the combination for treatment of HIV-1.

12.
Radiol Artif Intell ; : e230182, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38864741

RESUMO

"Just Accepted" papers have undergone full peer review and have been accepted for publication in Radiology: Artificial Intelligence. This article will undergo copyediting, layout, and proof review before it is published in its final version. Please note that during production of the final copyedited article, errors may be discovered which could affect the content. The University of California San Francisco Adult Longitudinal Post-Treatment Diffuse Glioma (UCSF-ALPTDG) MRI dataset is a publicly available annotated dataset featuring multimodal brain MRIs from 298 patients with diffuse gliomas taken at two consecutive follow-ups (596 scans total), with corresponding clinical history and expert voxelwise annotations. ©RSNA, 2024.

13.
J Infect Dis ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38853607

RESUMO

BACKGROUND: In a phase 3 trial, letermovir was non-inferior to valganciclovir for CMV disease prophylaxis in CMV-seronegative (R-) kidney transplant recipients (KTRs) who received a kidney from a CMV-seropositive donor (D+). Genotypic antiviral resistance and CMV glycoprotein B (gB) genotype are reported. METHODS: Plasma samples with detectable CMV DNA were sequenced for presence of known letermovir and valganciclovir resistance-associated amino acid substitutions (RASs) encoded by CMV gene regions (UL51, UL56, UL89, UL54, UL97) and prevalence of gB (UL55) genotypes (gB1-gB5). RESULTS: 84 of 292 participants in the letermovir and 93 of 297 in the valganciclovir group had evaluable data for ≥1 gene target. Letermovir RASs were not detected in participants who received letermovir prophylaxis; however, 3 had valganciclovir RASs (pUL97). Twelve participants in the valganciclovir group had valganciclovir RASs (pUL54, pUL97); and 1 who did not receive letermovir during the trial also had letermovir RASs (pUL56). All but 1 participant responded to valganciclovir treatment irrespective of breakthrough CMV DNAemia or frequency of RASs. gB1 was the most frequent genotype across all participants and subgroups. CONCLUSION: Letermovir RASs were not detected in the letermovir group, supporting a low risk for development of resistance with letermovir prophylaxis in CMV D+R- KTRs. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov: NCT03443869, EudraCT: 2017-001055-30.

14.
Langenbecks Arch Surg ; 409(1): 178, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38850452

RESUMO

PURPOSE: Limited data exist regarding the surgical outcomes of acute colonic pseudo-obstruction (ACPO), commonly referred to as Ogilvie syndrome, in modern clinical practice. The prevailing belief is that surgery should be avoided due to previously reported high mortality rates. We aimed to describe the surgical results of ACPO treated within our institution. METHODS: Our prospectively maintained colorectal surgery registry was queried for patients diagnosed with ACPO, who underwent surgery between 2009 and 2022. Postoperative complications were graded according to Clavien-Dindo (CD) classification. The primary outcome was postoperative mortality. RESULTS: A total of 32 patients who underwent surgery for ACPO were identified. Overall, nonoperative therapy was initially administered to 21 patients (65.6%). The surgeries performed included total abdominal colectomy (15, 43.1%), ascending colectomy with end ileostomy (8, 25%), transverse colostomy (5, 15.6%), ileostomy and transverse colostomy (3, 9.4%), and Hartmann's operation (1, 3.1%). Severe postoperative complications (CD grade 3 or 4) occurred in five patients (15.6%). No recurrence of ACPO was observed and no patient required reoperation. The average postoperative length of stay was 14.5 days, 30-day mortality was 6.3% (n = 2), and 90-day mortality was 15.6% (n = 5) due to complications of underlying comorbidities. CONCLUSIONS: Surgical treatment was effective for patients with ACPO refractory to medical therapy or presenting with acute complications. Although postoperative complications were frequent, both the 30- and 90-day mortality rates were lower than previously documented in the literature. Further investigations are warranted to determine the optimal surgical strategy, which may involve total or segmental colectomy, or diversion alone without resection.


Assuntos
Colectomia , Pseudo-Obstrução do Colo , Complicações Pós-Operatórias , Humanos , Pseudo-Obstrução do Colo/cirurgia , Pseudo-Obstrução do Colo/mortalidade , Masculino , Feminino , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Colectomia/métodos , Complicações Pós-Operatórias/etiologia , Doença Aguda , Resultado do Tratamento , Adulto , Idoso de 80 Anos ou mais , Tempo de Internação , Sistema de Registros
15.
PLoS One ; 19(6): e0305056, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38848400

RESUMO

This protocol presents a multilevel cluster randomized study in 24 communities in Cape Town, South Africa. The study comprises four specific aims. Aim 1, conducted during the formative phase, was to modify the original Couples Health CoOp (CHC) intervention to include antiretroviral therapy/pre-exposure prophylaxis (ART/PrEP), called the Couples Health CoOp Plus (CHC+), with review from our Community Collaborative Board and a Peer Advisory Board. Aim 1 has been completed for staging the trial. Aim 2 is to evaluate the impact of a stigma awareness and education workshop on community members' attitudes and behaviors toward young women and men who use AODs and people in their community seeking HIV services (testing/ART/PrEP) and other health services in their local clinics. Aim 3 is to test the efficacy of the CHC+ to increase both partners' PrEP/ART initiation and adherence (at 3 and 6 months) and to reduce alcohol and other drug use, sexual risk and gender-based violence, and to enhance positive gender norms and communication relative to HIV testing services (n = 480 couples). Aim 4 seeks to examine through mixed methods the interaction of the stigma awareness workshop and the CHC+ on increased PrEP and ART initiation, retention, and adherence among young women and their primary partners. Ongoing collaborations with community peer leaders and local outreach staff from these communities are essential for reaching the project's aims. Additionally, a manualized field protocol with regular training, fidelity checks, and quality assurance are critical components of this multilevel community trial for successful ongoing data collection. Trial registration. Clinicaltrials.gov Registration Number: NCT05310773. Pan African Trials: pactr.samrc.ac.za/ Registration Number: PACTR202205640398485.


Assuntos
Infecções por HIV , Humanos , Infecções por HIV/prevenção & controle , África do Sul , Feminino , Masculino , Adulto , Profilaxia Pré-Exposição/métodos , Estigma Social , Adulto Jovem , Adolescente , Parceiros Sexuais/psicologia , Fármacos Anti-HIV/uso terapêutico
16.
Body Image ; 50: 101741, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38850714

RESUMO

In this position paper, we review nonacademic and academic discourse on body neutrality, a recent concept that has spread from social media platforms into scientific publications. This discourse has (inaccurately) promulgated that body neutrality is distinct from and more realistic than positive body image and body positivity. We identify and challenge 10 myths found within this discourse: (1) positive body image and body positivity are the same and therefore interchangeable, (2) positive body image isn't realistic or attainable, (3) we should forget about body positivity and positive body image, (4) body neutrality is a new way of thinking about body image, (5) body neutrality is unique from positive body image and positivity, (6) body neutrality is a more realistic and inclusive alternative to positive body image and body positivity, (7) body neutrality is different from positive body image but we can still use the research on positive body image to support body neutrality, (8) body neutrality is a midpoint between negative body image and positive body image, (9) striving for body neutrality is sufficient, and (10) appearance can be disregarded. We offer recommendations applicable to researchers, clinicians, media, and the general public interested in body neutrality.


Assuntos
Imagem Corporal , Humanos , Imagem Corporal/psicologia , Mídias Sociais , Autoimagem
17.
Vet Comp Oncol ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890790

RESUMO

Although canine pituitary masses (PM) are increasingly treated with stereotactic radiotherapy (SRT), historical literature supports superior outcomes with conventional full-course fractionated radiation therapy (FRT). A multi-institutional retrospective study was performed, including dogs with PM treated from 2016 to 2022 with SRT (total dose 30 or 35 Gy in 5 daily fractions) or FRT (total dose 50-54 Gy in 19-20 daily fractions). The influence of potential prognostic/predictive factors was assessed, including pituitary: brain height, pituitary: brain volume, sex, age and endocrine status (functional [F] vs. nonfunctional [NF] PM). Forty-four dogs with PM were included (26 F, 14 NF, 4 unknown). All patients completed protocols as scheduled (SRT = 27, FRT = 17) and two dogs had suspected Grade 1 acute neurotoxicity. During the first 6 months after RT, 5/27 (19%) dogs treated with SRT (4 F, 1 NF) and 3/17 (18%) dogs treated with FRT (all F) died or were euthanised because of progressive neurologic signs. The overall median survival time was 608 days (95% CI, 375-840 days). Young age at the time of treatment was significant for survival (p = 0.0288); the overall median survival time was 753 days for dogs <9 years of age (95% CI, 614-892 days) and 445 days for dogs ≥9 years of age (95% CI, 183-707 days). Survival time was not associated with treatment type or any other factor assessed herein. A prospective study using standardised protocols would further validate the results of the present study and potentially elucidate the predictors of early death.

18.
Nature ; 630(8018): 831-835, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38768633

RESUMO

Observations of transiting gas giant exoplanets have revealed a pervasive depletion of methane1-4, which has only recently been identified atmospherically5,6. The depletion is thought to be maintained by disequilibrium processes such as photochemistry or mixing from a hotter interior7-9. However, the interiors are largely unconstrained along with the vertical mixing strength and only upper limits on the CH4 depletion have been available. The warm Neptune WASP-107b stands out among exoplanets with an unusually low density, reported low core mass10, and temperatures amenable to CH4, though previous observations have yet to find the molecule2,4. Here we present a JWST-NIRSpec transmission spectrum of WASP-107b that shows features from both SO2 and CH4 along with H2O, CO2, and CO. We detect methane with 4.2σ significance at an abundance of 1.0 ± 0.5 ppm, which is depleted by 3 orders of magnitude relative to equilibrium expectations. Our results are highly constraining for the atmosphere and interior, which indicate the envelope has a super-solar metallicity of 43 ± 8 × solar, a hot interior with an intrinsic temperature of Tint = 460 ± 40 K, and vigorous vertical mixing which depletes CH4 with a diffusion coefficient of Kzz = 1011.6±0.1 cm2 s-1. Photochemistry has a negligible effect on the CH4 abundance but is needed to account for the SO2. We infer a core mass of 11.5 - 3.6 + 3.0 M ⊕ , which is much higher than previous upper limits10, releasing a tension with core-accretion models11.

19.
J Neurophysiol ; 131(6): 1188-1199, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38691529

RESUMO

Prolonged inhibition of respiratory neural activity elicits a long-lasting increase in phrenic nerve amplitude once respiratory neural activity is restored. Such long-lasting facilitation represents a form of respiratory motor plasticity known as inactivity-induced phrenic motor facilitation (iPMF). Although facilitation also occurs in inspiratory intercostal nerve activity after diminished respiratory neural activity (iIMF), it is of shorter duration. Atypical PKC activity in the cervical spinal cord is necessary for iPMF and iIMF, but the site and specific isoform of the relevant atypical PKC are unknown. Here, we used RNA interference to test the hypothesis that the zeta atypical PKC isoform (PKCζ) within phrenic motor neurons is necessary for iPMF but PKCζ within intercostal motor neurons is unnecessary for transient iIMF. Intrapleural injections of siRNAs targeting PKCζ (siPKCζ) to knock down PKCζ mRNA within phrenic and intercostal motor neurons were made in rats. Control rats received a nontargeting siRNA (NTsi) or an active siRNA pool targeting a novel PKC isoform, PKCθ (siPKCθ), which is required for other forms of respiratory motor plasticity. Phrenic nerve burst amplitude and external intercostal (T2) electromyographic (EMG) activity were measured in anesthetized and mechanically ventilated rats exposed to 30 min of respiratory neural inactivity (i.e., neural apnea) created by modest hypocapnia (20 min) or a similar recording duration without neural apnea (time control). Phrenic burst amplitude was increased in rats treated with NTsi (68 ± 10% baseline) and siPKCθ (57 ± 8% baseline) 60 min after neural apnea vs. time control rats (-3 ± 3% baseline), demonstrating iPMF. In contrast, intrapleural siPKCζ virtually abolished iPMF (5 ± 4% baseline). iIMF was transient in all groups exposed to neural apnea; however, intrapleural siPKCζ attenuated iIMF 5 min after neural apnea (50 ± 21% baseline) vs. NTsi (97 ± 22% baseline) and siPKCθ (103 ± 20% baseline). Neural inactivity elevated the phrenic, but not intercostal, responses to hypercapnia, an effect that was blocked by siPKCζ. We conclude that PKCζ within phrenic motor neurons is necessary for long-lasting iPMF, whereas intercostal motor neuron PKCζ contributes to, but is not necessary for, transient iIMF.NEW & NOTEWORTHY We report important new findings concerning the mechanisms regulating a form of spinal neuroplasticity elicited by prolonged inhibition of respiratory neural activity, inactivity-induced phrenic motor facilitation (iPMF). We demonstrate that the atypical PKC isoform PKCζ within phrenic motor neurons is necessary for long-lasting iPMF, whereas intercostal motor neuron PKCζ contributes to, but is not necessary for, transient inspiratory intercostal facilitation. Our findings are novel and advance our understanding of mechanisms contributing to phrenic motor plasticity.


Assuntos
Neurônios Motores , Nervo Frênico , Proteína Quinase C , Ratos Sprague-Dawley , Animais , Nervo Frênico/fisiologia , Proteína Quinase C/metabolismo , Proteína Quinase C/fisiologia , Neurônios Motores/fisiologia , Masculino , Ratos , Plasticidade Neuronal/fisiologia
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