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1.
Int Wound J ; 21(7): e14956, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38949176

RESUMO

We investigated nurses' experiences of hospital-acquired pressure injury (PI) prevention in acute care services to better understand how PI prevention may be optimised. We used the Theoretical Domains Framework to systematically identify barriers and enablers to evidence-based preventive practices as required by the International Guideline. This study was one element of a complex capacity building project on PI surveillance and prevention within the acute health service partners of Monash Partners Academic Health Science Centre, an accredited academic health partnership located in Melbourne, Australia. We adopted a qualitative descriptive design. We interviewed 32 nurses that provided care in intensive care units, general wards and COVID wards of four acute care services. Nurses were recruited from four large acute care services (three public, one private) located in Melbourne. Most of them worked with patients who were at high risk of hospital-acquired PI on a daily basis. Interview transcripts were coded and analysed using thematic analysis guided by the Theoretical Domains Framework. The domains referred to most frequently by all participants included: Knowledge, Skills, Social/Professional Role and Identity, Beliefs about Capabilities, and Environmental Context and Resources. The key barriers discussed by nurses included gaps in nurses' knowledge and skills related to identification and staging of PI, heavy nursing workload and inadequate staffing levels, stigma and self-blame related to PI identification, and exacerbating impacts of the COVID-19 pandemic. Main facilitators discussed were training programmes, nursing audits and feedback, and teamwork. Participants suggested improvements including accessible and tailored training, visual reminders, and addressing heavy workloads and emotional barriers nurses face. Investing in tailored training initiatives to improve nurses' knowledge and organisational changes to address low level staffing and heavy workloads are urgently needed to support nurses in delivering optimal care and preventing hospital-acquired PI.


Assuntos
Úlcera por Pressão , Pesquisa Qualitativa , Humanos , Úlcera por Pressão/prevenção & controle , Vitória , Masculino , Feminino , Adulto , COVID-19/prevenção & controle , Recursos Humanos de Enfermagem Hospitalar/psicologia , Pessoa de Meia-Idade , Atitude do Pessoal de Saúde , Doença Iatrogênica/prevenção & controle
3.
Horm Behav ; 164: 105603, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39029339

RESUMO

Deficiencies in maternal nutrition have long-term consequences affecting brain development of the progeny and its behavior. In the present work, female mice were exposed to a normal-protein or a low-protein diet during gestation and lactation. We analyzed behavioral and molecular consequences of malnutrition in dams and how it affects female offspring at weaning. We have observed that a low-protein diet during pregnancy and lactation leads to anxiety-like behavior and anhedonia in dams. Protein malnutrition during the perinatal period delays physical and neurological development of female pups. Glucocorticoid levels increased in the plasma of malnourished female offspring but not in dams when compared to the control group. Interestingly, the expression of glucocorticoid receptor (GR) was reduced in hippocampus and amygdala on both malnourished dams and female pups. In addition, malnourished pups exhibited a significant increase in the expression of Dnmt3b, Gadd45b, and Fkbp5 and a reduction in Bdnf VI variant mRNA in hippocampus. In contrast, a reduction on Dnmt3b has been observed on the amygdala of weaned mice. No changes have been observed on global methylation levels (5-methylcytosine) in hippocampal genomic DNA neither in dams nor female offspring. In conclusion, deregulated behaviors observed in malnourished dams might be mediated by a low expression of GR in brain regions associated with emotive behaviors. Additionally, low-protein diet differentially deregulates the expression of genes involved in DNA methylation/demethylation machinery in female offspring but not in dams, providing an insight into regional- and age-specific mechanisms due to protein malnutrition.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Metilação de DNA , Hipocampo , Comportamento Materno , Efeitos Tardios da Exposição Pré-Natal , Receptores de Glucocorticoides , Proteínas de Ligação a Tacrolimo , Animais , Feminino , Gravidez , Camundongos , Receptores de Glucocorticoides/metabolismo , Receptores de Glucocorticoides/genética , Proteínas de Ligação a Tacrolimo/genética , Proteínas de Ligação a Tacrolimo/metabolismo , Comportamento Materno/fisiologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Hipocampo/metabolismo , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , Estresse Psicológico/metabolismo , Tonsila do Cerebelo/metabolismo , Dieta com Restrição de Proteínas , DNA Metiltransferase 3B , Deficiência de Proteína/metabolismo , Deficiência de Proteína/complicações , Ansiedade/etiologia , Glucocorticoides/metabolismo , Fenômenos Fisiológicos da Nutrição Materna/fisiologia , Transtornos do Neurodesenvolvimento/etiologia , Transtornos do Neurodesenvolvimento/metabolismo , Transtornos do Neurodesenvolvimento/genética , Animais Recém-Nascidos , Proteínas GADD45 , Antígenos de Diferenciação
4.
Obesity (Silver Spring) ; 32(7): 1281-1289, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38932724

RESUMO

OBJECTIVE: Higher intake of ultraprocessed foods (UPFs) is associated with obesity. We examined whether replacing UPFs (NOVA 4) with minimally processed foods and culinary ingredients (NOVA 1 + 2) was associated with differential weight change in this secondary prospective analysis of the Preventing Overweight Using Novel Dietary Strategies (POUNDS) Lost trial. METHODS: We estimated percent energy intake (%kcal) from the four NOVA groups using 24-h dietary recalls in a subset of 356 participants. Multivariable-adjusted substitution models examined whether replacing %kcal from UPFs with NOVA 1 + 2 was associated with greater weight, body fat percentage, trunk fat, and waist circumference reduction at 6 months; changes in parameters were compared among NOVA 1 + 2 tertiles (T). RESULTS: Participants were on average 52.3 years of age, 85% White, 55% female, and 58.2% nonsmoking, with a mean BMI of 32.7 kg/m2. Replacing 10%kcal of UPFs with NOVA 1 + 2 was associated with greater 6-month weight (ß = 0.51, 95% CI: -0.93 to -0.09, p = 0.02), body fat percentage (ß = 2.7, 95% CI: -5.10 to -0.43, p = 0.02), and trunk fat reduction (ß = 3.9, 95% CI: -7.01 to -0.70, p = 0.02), but not waist circumference reduction. Participants in T3 (-8.33 kg) versus T1 (-5.32 kg) of NOVA 1 + 2 had greater weight loss (p < 0.001). CONCLUSIONS: Isocaloric substitution of UPFs with NOVA 1 + 2 was associated with marginally greater weight loss under energy restriction. These modest findings support more research exploring the mechanisms linking UPFs with body weight regulation beyond energy intake.


Assuntos
Índice de Massa Corporal , Ingestão de Energia , Obesidade , Circunferência da Cintura , Redução de Peso , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Obesidade/dietoterapia , Estudos Prospectivos , Adulto , Manipulação de Alimentos/métodos , Dieta Redutora/métodos , Fast Foods/efeitos adversos , Sobrepeso/dietoterapia
6.
PLoS One ; 19(5): e0301718, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38768147

RESUMO

OBJECTIVE: To analyze the perceptions of professionals, caregivers, children, and adolescents with disabilities regarding the implementation of the My Abilities First (MAF) tool in Specialized Child Rehabilitation Centers (CERs). METHOD: This is a qualitative research based on Reflexive Thematic Analysis (RTA). The study involved twenty-seven intentionally selected individuals, comprising 12 physiotherapists, 4 occupational therapists, 11 caregivers, 9 children and 2 adolescents. Participants completed sociodemographic and clinical questionnaires and took part in semi-structured online interviews, focusing on two themes: Positive health approaches and the MAF tool. The study was approved by the local ethics committee (opinion 4.779.175). RESULTS: Reflexive Thematic Analysis of the interviews resulted in two themes: (1) Perceptions regarding the MAF tool as an educational and contributory process to enhance the inclusion and participation of children and adolescents with disabilities, and (2) Barriers and facilitators for the implementation process of the MAF tool. The implementation of MAF was identified as a driving factor in promoting equity and increased participation of children and adolescents with disabilities in various settings, including health, education, and leisure. Interviewees highlighted the need to confront attitudinal, communication, and social barriers that may hinder the implementation of the tool. CONCLUSION: The implementation of the MAF tool was perceived as an innovation due to its focus on the abilities of individuals with disabilities. However, there is a need to restructure it to broaden its scope and access to different contexts in order to confront barriers and enhance the inclusion and participation of children and adolescents with disabilities.


Assuntos
Cuidadores , Crianças com Deficiência , Pesquisa Qualitativa , Humanos , Adolescente , Criança , Feminino , Masculino , Cuidadores/psicologia , Crianças com Deficiência/psicologia , Adulto , Percepção , Pessoas com Deficiência/psicologia , Inquéritos e Questionários , Terapeutas Ocupacionais/psicologia
7.
J Natl Cancer Inst ; 116(8): 1333-1342, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38688563

RESUMO

BACKGROUND: Physical activity improves physical and psychological health in cancer survivors. This study evaluated Active Living After Cancer (ALAC), a community-based program to improve physical activity, physical function, and quality of life (QOL) in minority and medically underserved cancer survivors and their caregivers. METHODS: Participants completed 12 weekly ALAC sessions and assessments of physical activity, physical functioning, and QOL at baseline and follow-up (week 12). Paired samples t tests were used to assess changes in outcomes over time. RESULTS: A total of 540 cancer survivors (mean age = 61.1 [SD = 11.3] years) and 87 caregivers (mean age = 62.3 [SD = 13.1] years) were enrolled. Most were women (91.4%), Hispanic (61.1%) or non-Hispanic Black (19.3%), and medically underserved (86.4%). The percent of cancer survivors meeting physical activity recommendations increased from 28.9% to 60.2% (d = 0.75), and the number of sit-to-stand repetitions in a 30-second period increased from 12.3 to 14.3 (d = 0.39) from 0-12 weeks. Cancer survivors reported statistically significant improvements in physical (t score Δ = 1.7, d = 0.06) and mental (t score Δ = 2.3, d = 0.31) health-related QOL. Caregivers also improved their physical activity, physical function, and QOL, and there were no statistically significant differences between breast and other cancer survivors and between cancer survivors and caregivers. CONCLUSIONS: The ALAC program demonstrated increased physical activity, physical function, and QOL in medically underserved cancer survivors and their caregivers. Furthermore, ALAC was successfully implemented by community partners and serves as a good model for reaching medically underserved cancer survivors and improving survivorship. Additional efforts are warranted to further extend reach, improve cancer survivorship, and reduce cancer health disparities among underserved cancer survivors.


Assuntos
Sobreviventes de Câncer , Cuidadores , Exercício Físico , Neoplasias , Qualidade de Vida , Humanos , Feminino , Sobreviventes de Câncer/psicologia , Pessoa de Meia-Idade , Masculino , Cuidadores/psicologia , Neoplasias/psicologia , Neoplasias/terapia , Idoso , Área Carente de Assistência Médica
8.
Anal Methods ; 16(13): 1880-1886, 2024 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-38469698

RESUMO

The study of ibuprofen (IBU) preconcentration was carried out making use of a homemade column for solid-phase extraction (SPE), using vermiculite (VT) or organo-vermiculites (OVTs) as sorbent phases. Aqueous samples (50.0 mL) percolated the column and IBU was sorbed onto the VT or OVT and then desorbed using acetonitrile. Employing this SPE system and OVT, calibration curves were generated for IBU, by spectrophotometric quantification using the α-naphthylamine method. R2 values higher than 0.9950 and LOD between 12 and 18 µg L-1 were observed, for real enrichment factors of 21 and 31, by using OVTs. The analytical protocol was applied to three water samples, which were spiked with IBU solutions to evaluate the precision and accuracy of the method. Recoveries between 77 and 110% at three different IBU concentrations and RSD lower than 18% were observed, even by using the spectrophotometric method. The protocol developed in this study demonstrated that the OVT was appropriate to work as a preconcentration phase for IBU determination in water samples.


Assuntos
Ibuprofeno , Água , Silicatos de Alumínio , Extração em Fase Sólida/métodos
9.
Int J Mol Sci ; 25(3)2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38338764

RESUMO

The kallikrein-kinin system is a versatile regulatory network implicated in various biological processes encompassing inflammation, nociception, blood pressure control, and central nervous system functions. Its physiological impact is mediated through G-protein-coupled transmembrane receptors, specifically the B1 and B2 receptors. Dopamine, a key catecholamine neurotransmitter widely distributed in the CNS, plays a crucial role in diverse physiological functions including motricity, reward, anxiety, fear, feeding, sleep, and arousal. Notably, the potential physical interaction between bradykinin and dopaminergic receptors has been previously documented. In this study, we aimed to explore whether B2R modulation in catecholaminergic neurons influences the dopaminergic pathway, impacting behavioral, metabolic, and motor aspects in both male and female mice. B2R ablation in tyrosine hydroxylase cells reduced the body weight and lean mass without affecting body adiposity, substrate oxidation, locomotor activity, glucose tolerance, or insulin sensitivity in mice. Moreover, a B2R deficiency in TH cells did not alter anxiety levels, exercise performance, or motor coordination in female and male mice. The concentrations of monoamines and their metabolites in the substantia nigra and cortex region were not affected in knockout mice. In essence, B2R deletion in TH cells selectively influenced the body weight and composition, leaving the behavioral and motor aspects largely unaffected.


Assuntos
Receptor B2 da Bradicinina , Tirosina 3-Mono-Oxigenase , Camundongos , Masculino , Feminino , Animais , Receptor B2 da Bradicinina/genética , Receptor B2 da Bradicinina/metabolismo , Tirosina 3-Mono-Oxigenase/genética , Bradicinina/farmacologia , Receptor B1 da Bradicinina/metabolismo , Peso Corporal , Camundongos Knockout
10.
J Adv Nurs ; 80(4): 1262-1282, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37788102

RESUMO

AIM(S): To: (1) explore current best practices for hospital-acquired pressure injury prevention in high BMI patients; (2) summarize nurses' experiences in preventing and managing them; (3) explore the association between a high BMI and occurrence and severity of pressure injury. DESIGN: Exploratory. METHODS: Scoping review. DATA SOURCES: Ovid MEDLINE, EBSCO CINAHL Plus, JBI Evidence Synthesis, Scopus, Embase, clinical registries and grey literature (search dates: January 2009 to May 2021). RESULTS: Overall, 1479 studies were screened. The included studies were published between 2010 and 2022. Five interventional studies and 32 best practice recommendations (Objective 1) reported low-quality evidence. Findings of thematic analysis reported in nine studies (Objective 2) identified nurses' issues as insufficient bariatric equipment, inadequate staffing, weight bias, fatigue, obese-related terminology issues, ethical dilemmas and insufficient staff education in high BMI patients' pressure injury prevention. No association between hospital-acquired pressure injury occurrence and high BMI were reported by 18 out of 28 included studies (Objective 3). CONCLUSION: Quality of evidence was low for the interventional studies and best practice recommendations. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Current (2019) International Pressure Injury Guideline to be used despite the low quality of evidence of most best practice recommendations. IMPACT STATEMENT: This study addressed hospital-acquired pressure injury prevention in high BMI patients. Greater proportion of studies in this review found no association between high BMI and occurrence of hospital-acquired pressure injury. Nurses need educational interventions on pressure injury prevention in high body mass index people, sufficient staffing for repositioning and improved availability of bariatric equipment. REPORTING METHOD: We adhered to relevant EQUATOR guidelines, PRISMA extension for scoping reviews. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. WHAT DOES THIS PAPER CONTRIBUTE TO THE WIDER GLOBAL CLINICAL COMMUNITY?: Larger clinical trials are needed on repositioning frequency, support surfaces, prophylactic dressings and risk assessment tools to inform clinical practice guidelines on pressure injury prevention in high BMI people. PROTOCOL REGISTRATION: Wound Practice and Research (https://doi.org/10.33235/wpr.29.3.133-139).


Assuntos
Úlcera por Pressão , Humanos , Úlcera por Pressão/prevenção & controle , Úlcera por Pressão/epidemiologia , Índice de Massa Corporal , Bandagens , Hospitais
11.
Blood Adv ; 8(3): 703-707, 2024 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-38052037

RESUMO

ABSTRACT: The total therapy (TT) IIIB phase 2 study incorporated bortezomib into tandem melphalan-based hematopoietic stem cell transplantation with dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, and etoposide for induction/consolidation and bortezomib, lenalidomide, and dexamethasone (VRD) for maintenance in patients with newly diagnosed multiple myeloma (MM). This updated analysis presents a 15.4-year median follow-up. Of 177 patients, 21% patients had gene expression profile (GEP)-defined high-risk MM. 15-year progression free survival (PFS) was 27.9%. Median PFS was better in GEP-defined low-risk patients at 7.8 years and in International Staging System stage 1 patients at 8.7 years. Overall, median OS was 9.1 years, and 15-year overall survival (OS) was 35.9%. GEP-defined low-risk patients' median OS was 11.2 years, and that of GEP-defined high-risk patients was 2.8 years. There was no difference in OS between TT IIIB and TT IIIA. This study includes the longest follow-up of patients treated with maintenance VRD reported to date. In patients with GEP-defined low-risk, nearly half and one-third of patients without ongoing treatment showed no signs of progression at 10 and 15 years, respectively. One-third of patients survived more than 15 years, but 3 years of VRD maintenance did not improve outcomes for patients with GEP-defined high-risk MM. The study was registered on www.clinicaltrials.gov as #NCT00572169.


Assuntos
Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/diagnóstico , Bortezomib/uso terapêutico , Seguimentos , Dexametasona/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
12.
Neurobiol Stress ; 28: 100587, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38075022

RESUMO

Anxiety, a state related to anticipatory fear, can be adaptive in the face of environmental threats or stressors. However, anxiety can also become persistent and manifest as anxiety- and stress-related disorders, such as generalized anxiety or post-traumatic stress disorder (PTSD). In rodents, systemic administration of glucocorticoids (GCs) or short-term restraint stress induces anxiety-like behaviors and dendritic branching within the basolateral complex of the amygdala (BLA) ten days later. Additionally, increased arousal-related memory retention mediated by elevated GCs requires concomitant noradrenaline (NE) signaling, both acting in the BLA. It is unknown whether GCs and NE play a role in the delayed acute stress-induced effects on behavior and BLA dendritic plasticity. Here, inhibiting corticosterone (CORT) elevation during 2 h of restraint stress prevents stress-induced increases in delayed anxiety-like behavior and BLA dendritic spine density in rats. Also, we show that the delayed acute stress-induced effects on behavior and morphological alterations are critically dependent on genomic glucocorticoid receptor (GR) actions in the BLA. Unlike CORT, the pharmacological enhancement of NE signaling in the BLA was insufficient to drive delayed anxiety-related behavior. Nonetheless, the delayed anxiety-like behavior ten days after acute stress requires NE signaling in the BLA during stress exposure. Therefore, we define the essential roles of two stress-related hormones for the late stress consequences, acting at two separate times: CORT, via GR, immediately during stress, and NE, via beta-adrenoceptors, during the expression of delayed anxiety.

13.
Neurourol Urodyn ; 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38048061

RESUMO

AIMS: Lower urinary tract dysfunctions (LUTD) are very common and, importantly, affect patients' quality of life (QoL). LUTD can range from urinary retention to urgency incontinence and includes a variety of symptoms. Nerve stimulation (NS) is an accepted widespread treatment with documented success for LUTD and is used widely. The aim of this review is to report the results of the discussion about how to improve the outcomes of NS for LUTD treatment. METHODS: During its 2023 meeting in Bristol, the International Consultation on Incontinence Research Society discussed a literature review, and there was an expert consensus discussion focused on the emerging awareness of NS suitable for LUTD. RESULTS: The consensus discussed how to improve techniques and patients' selection in NS, and high-priority research questions were identified. CONCLUSIONS: Technique improvement, device programming, and patient selection are the goals of the current approach to NS. The conditional nerve stimulation with minimally invasive wireless systems and tailored algorithms hold promise for improving NS for LUTD, particularly for patients with neurogenic bladder who represent the new extended population to be treated.

14.
Healthcare (Basel) ; 11(23)2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-38063579

RESUMO

We aimed to explore managerial and project staff perceptions of the pilot implementation of an algorithm-supported care navigation model, targeting people at risk of hospital readmission. The pilot was implemented from May to November 2017 at a Victorian health service (Australia) and provided to sixty-five patients discharged from the hospital to the community. All managers and the single clinician involved participated in a semi-structured interview. Participants (n = 6) were asked about their perceptions of the service design and the enablers and barriers to implementation. Interviews were transcribed verbatim and analysed according to a framework approach, using inductive and deductive techniques. Constructed themes included the following: an algorithm alone is not enough, the health service culture, leadership, resources and the perceived patient experience. Participants felt that having an algorithm to target those considered most likely to benefit was helpful but not enough on its own without addressing other contextual factors, such as the health service's capacity to support a large-scale implementation. Deductively mapping themes to the integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) framework highlighted that a formal facilitation would be essential for future sustainable implementations. The systematic identification of barriers and enablers elicited critical information for broader implementations of algorithm-supported models of care.

15.
Am J Hosp Palliat Care ; : 10499091231220255, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38048776

RESUMO

BACKGROUND: Approximately 6.7 million American adults are living with heart failure (HF). Current therapies are geared toward preventing progression and managing symptoms, as there is no cure. Multiple studies have shown the benefit of including palliative care (PC) in patients with HF to improve symptoms and quality of life. Heart failure guidelines recommend the inclusion of PC in therapy, but referrals are often delayed. A previous pilot project demonstrated increased involvement of PC when targeted education was given to patients with HF. OBJECTIVE: Educate patients with HF on PC and examine the impact on PC consults, readmission, mortality, intensive care unit (ICU) transfers and evaluate sustainability of the intervention. METHODS: Patients (n = 124) admitted to an academic hospital with a diagnosis of HF were asked to view an educational module on PC. Patients who completed the module were placed in the intervention group (n = 39). Patients who declined were placed in the usual care group (n = 38). The number of PC consults, re-admissions, mortality, and transfers to the ICU were compared among participants and those who declined. Results were compared to previous pilot project. RESULTS: Eleven patients in the intervention group (IG) requested a PC consult vs one in the usual care group (UCG) (P = .006). There was no statistically significant difference in readmissions, mortality, or ICU transfers between groups. CONCLUSIONS: This sustainable project again demonstrated education on PC increases utilization of PC but does not statistically impact mortality, re-admissions, or transfers to higher levels of care.

17.
Hum Mol Genet ; 32(24): 3312-3322, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37658766

RESUMO

Autism spectrum disorders (ASD) are polygenic multifactorial disorders influenced by environmental factors. ASD-related differential DNA methylation has been found in human peripheral tissues, such as placenta, paternal sperm, buccal epithelium, and blood. However, these data lack direct comparison of DNA methylation levels with brain tissue from the same individual to determine the extent that peripheral tissues are surrogates for behavior-related disorders. Here, whole genome methylation profiling at all the possible sites throughout the mouse genome (>25 million) from both brain and blood tissues revealed novel insights into the systemic contributions of DNA methylation to ASD. Sixty-six differentially methylated regions (DMRs) share the same genomic coordinates in these two tissues, many of which are linked to risk genes for neurodevelopmental disorders and intellectual disabilities (e.g. Prkch, Ptn, Hcfc1, Mid1, and Nfia). Gene ontological pathways revealed a significant number of common terms between brain and blood (N = 65 terms), and nearly half (30/65) were associated with brain/neuronal development. Furthermore, seven DMR-associated genes among these terms contain methyl-sensitive transcription factor sequence motifs within the DMRs of both tissues; four of them (Cux2, Kcnip2, Fgf13, and Mrtfa) contain the same methyl-sensitive transcription factor binding sequence motifs (HES1/2/5, TBX2 and TFAP2C), suggesting DNA methylation influences the binding of common transcription factors required for gene expression. Together, these findings suggest that peripheral blood is a good surrogate tissue for brain and support that DNA methylation contributes to altered gene regulation in the pathogenesis of ASD.


Assuntos
Transtorno Autístico , Metilação de DNA , Gravidez , Feminino , Masculino , Humanos , Animais , Camundongos , Metilação de DNA/genética , Transtorno Autístico/genética , Epigênese Genética , Sêmen , Fatores de Transcrição/genética , Hipocampo
18.
J Neurosci ; 43(40): 6816-6829, 2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37625855

RESUMO

Dysfunctions in growth hormone (GH) secretion increase the prevalence of anxiety and other neuropsychiatric diseases. GH receptor (GHR) signaling in the amygdala has been associated with fear memory, a key feature of posttraumatic stress disorder. However, it is currently unknown which neuronal population is targeted by GH action to influence the development of neuropsychiatric diseases. Here, we showed that approximately 60% of somatostatin (SST)-expressing neurons in the extended amygdala are directly responsive to GH. GHR ablation in SST-expressing cells (SSTΔGHR mice) caused no alterations in energy or glucose metabolism. Notably, SSTΔGHR male mice exhibited increased anxiety-like behavior in the light-dark box and elevated plus maze tests, whereas SSTΔGHR females showed no changes in anxiety. Using auditory Pavlovian fear conditioning, both male and female SSTΔGHR mice exhibited a significant reduction in fear memory. Conversely, GHR ablation in SST neurons did not affect memory in the novel object recognition test. Gene expression was analyzed in a micro punch comprising the central nucleus of the amygdala (CEA) and basolateral (BLA) complex. GHR ablation in SST neurons caused sex-dependent changes in the expression of factors involved in synaptic plasticity and function. In conclusion, GHR expression in SST neurons is necessary to regulate anxiety in males, but not female mice. GHR ablation in SST neurons also decreases fear memory and affects gene expression in the amygdala, although marked sex differences were observed. Our findings identified for the first time a neurochemically-defined neuronal population responsible for mediating the effects of GH on behavioral aspects associated with neuropsychiatric diseases.SIGNIFICANCE STATEMENT Hormone action in the brain regulates different neurological aspects, affecting the predisposition to neuropsychiatric disorders, like depression, anxiety, and posttraumatic stress disorder. Growth hormone (GH) receptor is widely expressed in the brain, but the exact function of neuronal GH action is not fully understood. Here, we showed that mice lacking the GH receptor in a group of neurons that express the neuropeptide somatostatin exhibit increased anxiety. However, this effect is only observed in male mice. In contrast, the absence of the GH receptor in somatostatin-expressing neurons decreases fear memory, a key feature of posttraumatic stress disorder, in males and females. Thus, our study identified a specific group of neurons in which GH acts to affect the predisposition to neuropsychiatric diseases.


Assuntos
Hormônio do Crescimento , Somatostatina , Feminino , Masculino , Camundongos , Animais , Somatostatina/metabolismo , Hormônio do Crescimento/metabolismo , Ansiedade , Medo , Receptores da Somatotropina/genética , Receptores da Somatotropina/metabolismo , Neurônios/metabolismo
19.
Exp Neurol ; 368: 114481, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37463612

RESUMO

Early-life adversity, like perinatal protein malnutrition, increases the vulnerability to develop long-term alterations in brain structures and function. This study aimed to determine whether perinatal protein malnutrition predisposes to premature aging in a murine model and to assess the cellular and molecular mechanisms involved. To this end, mouse dams were fed either with a normal (NP, casein 20%) or a low-protein diet (LP, casein 8%) during gestation and lactation. Female offspring were evaluated at 2, 7 and 12 months of age. Positron emission tomography analysis showed alterations in the hippocampal CA3 region and the accessory olfactory bulb of LP mice during aging. Protein malnutrition impaired spatial memory, coinciding with higher levels of reactive oxygen species in the hippocampus and sirt7 upregulation. Protein malnutrition also led to higher senescence-associated ß-galactosidase activity and p21 expression. LP-12-month-old mice showed a higher number of newborn neurons that did not complete the maturation process. The social-odor discrimination in LP mice was impaired along life. In the olfactory bulb of LP mice, the senescence marker p21 was upregulated, coinciding with a downregulation of Sirt2 and Sirt7. Also, LP-12-month-old mice showed a downregulation of catalase and glutathione peroxidase, and LP-2-month-old mice showed a higher number of newborn neurons in the subventricular zone, which then returned to normal values. Our results show that perinatal protein malnutrition causes long-term impairment in cognitive and olfactory skills through an accelerated senescence phenotype accompanied by an increase in oxidative stress and altered sirtuin expression in the hippocampus and olfactory bulb.


Assuntos
Senilidade Prematura , Desnutrição , Gravidez , Camundongos , Animais , Feminino , Memória Espacial , Senilidade Prematura/genética , Caseínas/metabolismo , Estresse Oxidativo , Transtornos da Memória/etiologia , Bulbo Olfatório/fisiologia , Desnutrição/complicações , Desnutrição/metabolismo
20.
J Pediatr Urol ; 19(5): 639.e1-639.e4, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37419833

RESUMO

INTRODUCTION: Urinary drainage is usually left in place after laparoscopic pyeloplasty to limit the risk of complications, such as urinary leakage. The procedure is sometimes laborious and complications may occur. PURPOSE: Prospective evaluation of the Kirschner technique for urinary drainage during pediatric laparoscopic pyeloplasty. STUDY DESIGN: This technique (Upasani et al., J Pediatr Urol 2018) involves introducing a nephrostomy tube (Blue Stent) with a Kirschner wire during laparoscopic transperitoneal pyeloplasty. We evaluated this technique by analyzing 14 consecutive pyeloplasties (53% on female patients, median age 10 years (6-16 years), on the right side in 40%) performed by a single operator between 2018 and 2021. The drain and urinary catheter were clamped and the perirenal drain removed on day 2. The stent was removed during consultation between days 7 and 15. RESULTS: The median duration of surgery was 155 ± 7 min. Urinary drainage was installed within 5 min, without the need for radiological control and with no complications. All drains were correctly placed, with no drain migration or urinoma. Median hospital stay was 2 ± 1 days. One patient developed pyelonephritis (D8). The stent was removed without difficulty or complications. One patient presented an 8-mm lower calyx urinary stone at two months, revealed by macroscopic hematuria, necessitating extracorporeal shock wave lithotripsy. DISCUSSION: The study design was based on a homogeneous series of patients, without comparison with another drainage technique or procedures performed by another operator. A comparison with other techniques might have been informative. Before this study, we tested various types of urinary drainage, to optimize performance. This technique was considered the simplest and least invasive. CONCLUSION: External drain placement with this technique was rapid, safe, and reproducible in children. It also made it possible to test the tightness of the anastomosis and to avoid the need for anesthesia for drain removal.


Assuntos
Laparoscopia , Obstrução Ureteral , Criança , Feminino , Humanos , Fios Ortopédicos/efeitos adversos , Drenagem , Pelve Renal/cirurgia , Laparoscopia/métodos , Estudos Retrospectivos , Stents/efeitos adversos , Obstrução Ureteral/cirurgia , Procedimentos Cirúrgicos Urológicos/métodos , Adolescente
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