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1.
Front Surg ; 11: 1391971, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38726469

RESUMO

Background: A limiting factor in expanding the kidney donor pool is donor kidneys with renal tumors or cysts. Partial nephrectomy (PN) to remove these lesions prior to transplantation may help optimize organ usage without recurrence of malignancy or increased risk of complications. Methods: We retrospectively analyzed all recipients of a living or deceased donor graft between February 2009 and October 2022 in which a PN was performed prior to transplant due to the presence of one or more concerning growths. Donor and recipient demographics, perioperative data, donor allograft pathology, and recipient outcomes were obtained. Results: Thirty-six recipients received a graft in which a PN was performed to remove suspicious masses or cysts prior to transplant. Majority of pathologies turned out to be a simple renal cyst (65%), followed by renal cell carcinoma (15%), benign multilocular cystic renal neoplasm (7.5%), angiomyolipoma (5%), benign renal tissue (5%), and papillary adenoma (2.5%). No renal malignancy recurrences were observed during the study period (median follow-up: 67.2 months). Fourteen complications occurred among 11 patients (30.6% overall) during the first 6mo post-transplant. Mean eGFR (± standard error) at 36 months post-transplant was 51.9 ± 4.2 ml/min/1.73 m2 (N = 23). Three death-censored graft losses and four deaths with a functioning graft and were observed. Conclusion: PN of renal grafts with suspicious looking masses or cysts is a safe option to optimize organ usage and decrease the kidney non-use rate, with no observed recurrence of malignancy or increased risk of complications.

2.
Int J Surg ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38597387

RESUMO

BACKGROUND: At our center, surgical modifications to the conventional kidney transplant technique were developed with two goals in mind: to minimize the risk of developing post-transplant urologic/vascular/other surgical complications, and to simultaneously eliminate the need for initial ureteral stent placement and surgical drainage. METHODS: Here, we describe these modifications along with(what we believe are) their advantages over the conventional technique: creating an abdominal flap for easier abdominal closure(reflecting the parietal peritoneum from the abdominal wall), mobilizing the bladder before transplant(creating more space for bladder dissection, allowing it to move upward during abdominal wall closure), minimizing the dissection of iliac vessels to only anterior lymphatic tissue(attempting to minimize the incidence of fluid collections), using plastic arterial vascular bulldog clamps(causing less trauma to the iliac artery), performing vascular anastomosis of the renal artery first(making it easier for the surgeon to perform this anastomoses), creating longer ureteral spatulation, and inclusion of bladder mucosa along with some detrusor muscle layer in performing the ureteral anastomosis(attempting to minimize the incidence of urologic complications). Of note, no initial ureteral stent placement or surgical drainage was used. We report our experience during the first 12mo post-transplant of a single transplant surgeon who used each of these modifications among 707 consecutive recipients of kidney-alone transplants at our center since 2014. RESULTS: During the first 12mo post-transplant, 2.3%(16/707) of patients developed a urologic complication; only 1.0%(7/707) required surgical repair of their original ureteroneocystostomy. Additionally, 2.7%(19/707) developed a vascular complication; 8.8%(62/707) developed some other type of surgical complication(wound complication, lymphocele development, or development of a peri-renal hematoma or peri-renal collection). These overall results were clearly advantageous when compared with other studies. CONCLUSION: We believe that this modified kidney transplant technique clearly helped in reducing post-transplant risks of developing urologic/vascular/other surgical complications. Importantly, these results were achieved without initial ureteral stent placement or surgical drainage.

5.
J Appl Microbiol ; 135(5)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38658191

RESUMO

AIMS: The research aimed to optimize the ultrasound-assisted extraction of secondary metabolites and the antibacterial activity of the plant species Geranium robertianum. The phytochemical profiles of the optimized extracts, as well as their antibacterial and synergistic activity with an antibiotic and their potential mechanisms of action and cytotoxicity, were examined. METHODS AND RESULTS: Response Surface Methodology was used to optimize extraction conditions. Optimized ethanol and acetone extracts were tested via microdilution, checkerboard, time-kill kinetics, and cell membrane permeability methods. The extracts displayed broad antibacterial activity with minimum inhibitory concentrations ranging from 1.25 to 20 mg ml-1. In addition, the extract synergistically reacted with gentamicin against gentamicin-resistant strains of Escherichia coli and Staphylococcus aureus, enhancing the efficacy of the antibiotic up to 32-fold. The extracts demonstrated strain-dependent bactericidal activity in a 24-h time interval. They increase the permeability of the cell membrane, thus disrupting its normal functioning. The cytotoxic concentration (CC50) on human keratinocytes was 1771.24 ± 5.78 µg ml-1 for ethanol extract, and 958.01 ± 6.14 µg ml-1 for acetone extract. Kaempferol, ellagic acid, quercetin, and rutin were recognized as the main components in both extracts. CONCLUSIONS: The findings of this study indicate that the extracts of G. robertianum can be considered as potential natural antibacterial agents in the control of microorganisms.


Assuntos
Antibacterianos , Escherichia coli , Geranium , Testes de Sensibilidade Microbiana , Extratos Vegetais , Staphylococcus aureus , Antibacterianos/farmacologia , Geranium/química , Extratos Vegetais/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Humanos , Escherichia coli/efeitos dos fármacos , Gentamicinas/farmacologia , Queratinócitos/efeitos dos fármacos
6.
J Exp Zool B Mol Dev Evol ; 342(4): 335-341, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38686706

RESUMO

Evolutionary developmental biology (Evo-Devo) is flourishing in Latin America, particularly Argentina, where researchers are leveraging this integrative field to unlock the secrets of the region's remarkable biodiversity. A recent symposium held at the 5th Argentinean Meeting on Evolutionary Biology (RABE V) showcased a vibrant Evo-Devo community and the diversity of its research endeavors. The symposium included 3 plenary talks, 3 short talks, and 12 posters, and spanned a range of organisms and approaches. Interestingly, the symposium highlighted a prevalence of "top-down" Evo-Devo studies in the region, where researchers first analyze existing diversity and then propose potential developmental mechanisms. This approach, driven in part by financial constraints and the region's historical focus on natural history, presents a unique opportunity to bridge disciplines like comparative biology, paleontology, and botany. The symposium's success underscores the vital role of Evo-Devo in Latin America, not only for advancing our understanding of evolution but also for providing valuable tools to conserve and manage the region's irreplaceable biodiversity. As Evo-Devo continues to grow in Latin America, fostering collaboration and knowledge exchange within the region and beyond will be crucial for realizing the full potential of this transformative field.


Assuntos
Evolução Biológica , Biologia do Desenvolvimento , Argentina , Biodiversidade , Animais
7.
J Mot Behav ; : 1-15, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38565202

RESUMO

There are numerous studies comparing young and old adults in terms of muscle coordination in standard tasks (e.g., walking, reaching) and small variations of them. These tasks might hide differences: individuals would converge to similar behavior as they practice these throughout life. Also, we are unaware of studies that considered the muscle recruitment nested dynamics. For this reason, our study evaluated how young and old women coordinate and control the movement system while performing an unusual redundant motor control task through the network physiology approach. We acquired electromyographic signals from nine leg muscles of the dominant and non-dominant limbs during maximum voluntary isometric contractions (knee extension and flexion) and co-contraction bouts. Our results showed that young participants presented higher peak torque output, with similar EMG variability, compared to older participants. Considering firing rate frequencies, old and young women demonstrated different traits for network clustering and efficiency for the task. Age seems to affect muscle coordination at higher frequencies, even with a similar number of muscle synergies, indicating that younger women might have more integrated synergies than older women. The findings also point to differential muscle coordination adaptability.

8.
Nutr J ; 23(1): 42, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38627669

RESUMO

BACKGROUND: The Global Diet Quality Score (GDQS) was developed to be a simple, timely and cost-effective tool to track, simultaneously, nutritional deficiency and non-communicable disease risks from diet in diverse settings. The objective was to investigate the performance of GDQS as an indicator of adequate nutrient intake and dietary quality in a national-representative sample of the Brazilian population. METHODS: Nationally-representative data from 44,744 men and non-pregnant and non-lactating women aging ≥ 10 years, from the Brazilian National Dietary Survey were used. Dietary data were collected through two 24-h recalls (24HR). The GDQS was calculated and compared to a proxy indicator of nutrient adequate intake (the Minimum Dietary Diversity for Women-MDD-W) and to an indicator of high-risk diet for non-communicable diseases (caloric contribution from ultra-processed foods-UPF). To estimate the odds for overall nutrient inadequacy across MDD-W and GDQS quintiles, a multiple logistic regression was applied, and the two metrics' performances were compared using Wald's post-test. RESULTS: The mean GDQS for Brazilians was 14.5 (0-49 possible range), and only 1% of the population had a low-risk diet (GDQS ≥ 23). The GDQS mean was higher in women, elderly individuals and in higher-income households. An inverse correlation was found between the GDQS and UPF (rho (95% CI) = -0.20(-0.21;-0.19)). The odds for nutrient inadequacy were lower as quintiles of GDQS and MDD-W were higher (p-trend < 0.001), and MDD-W had a slightly better performance than GDQS (p-diff < 0.001). Having a low-risk GDQS (≥ 23) lowered the odds for nutrient inadequacy by 74% (95% CI:63%-81%). CONCLUSION: The GDQS is a good indicator of overall nutrient adequacy, and correlates well with UPF in a nationally representative sample of Brazil. Future studies must investigate the relationship between the GDQS and clinical endpoints, strengthening the recommendation to use this metric to surveillance dietary risks.


Assuntos
Dieta , Desnutrição , População da América do Sul , Masculino , Humanos , Feminino , Idoso , Ingestão de Energia , Ingestão de Alimentos
9.
Biol Sport ; 41(2): 115-121, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38524826

RESUMO

Previous training studies with comprehensive stretching durations have reported that an increase in range of motion (ROM) can be related to decreases in muscle stiffness. Therefore, the purpose of this study was to analyze the association between the passive muscle stiffness of three muscle groups (triceps surae, quadriceps, hamstrings) to the respective joint ROM. Thirty-six healthy male soccer players volunteered in this study. After a standardized warm-up, the muscle stiffness was tested via shear wave elastography in six muscles (gastrocnemius medialis and lateralis, rectus femoris, semitendinosus, semimembranosus, and biceps femoris long head). The hip extension, hip flexion, and ankle dorsiflexion ROM were also assessed with a modified Thomas test, a sit and reach test, and a standing wall push test, respectively. We found significant moderate to large correlations between hip flexion ROM and muscle stiffness for the semimembranosus (rP = -0.43; P = 0.01), biceps femoris long head (rP = -0.45; P = 0.01), and overall hamstring stiffness (rP = -0.50; P < 0.01). No significant correlations were found for triceps surae (rP = -0.12; P = 0.51 to 0.67) and rectus femoris muscle stiffness (rP = 0.25; P = 0.14) with ankle dorsiflexion and hip extension ROM, respectively. We conclude that muscle stiffness is an important contributor to hip flexion ROM, but less important for hip extension or ankle joint ROM. Additional contributors to ROM might be tendon stiffness or stretch/pain tolerance.

10.
World J Surg Oncol ; 22(1): 76, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38454471

RESUMO

BACKGROUND: The gold standard treatment for renal cell carcinoma (RCC) with tumor thrombus (TT) is complete surgical excision. The surgery is complex and challenging to the surgeon, especially with large tumor thrombus extending into the inferior vena cava (IVC) and right atrium. Traditionally, these difficult cases required the use of cardiopulmonary bypass (CPB) with or without deep hypothermic cardiac arrest, but in recent years, different surgical techniques derived from the field of liver transplantation have been used in efforts to avoid CPB. CASE PRESENTATION: We present a case of RCC with TT level IIIc (extending above major hepatic veins) that "uncoiled" intraoperatively into the right atrium after division of the IVC ligament, transforming into a level IV TT. Despite the new TT extension, the surgery was successfully completed exclusively through an abdominal approach without CPB and while using intraoperative transesophageal echocardiography (TEE) monitoring and a cardiothoracic team standby. CONCLUSIONS: This case highlights the need for a multidisciplinary approach and the utility of intraoperative continous TEE monitoring which helped to visualize the change of the TT venous extension, allowing the surgical teamto modify their surgical approach as needed avoiding a catastrophic event.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Células Neoplásicas Circulantes , Trombose , Humanos , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/patologia , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Nefrectomia/métodos , Trombose/diagnóstico por imagem , Trombose/etiologia , Trombose/cirurgia , Veia Cava Inferior/diagnóstico por imagem , Veia Cava Inferior/cirurgia , Veia Cava Inferior/patologia , Trombectomia/métodos , Células Neoplásicas Circulantes/patologia
11.
Front Physiol ; 15: 1349426, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38510941

RESUMO

This study aimed to investigate the correlation between the passive muscle stiffness of the pectoralis major muscle pars clavicularis (PMc) and shoulder extension range of motion (ROM) in both male and female participants. Thirty-nine (23 male/16 female) physically active and healthy participants volunteered in this study. After a standardized warm-up, the PMc stiffness was tested via shear wave elastography at a slightly stretched position (long muscle length) and in a non-stretched position (short muscle length). Additionally, a custom-made device and 3D motion capture assessed the active shoulder extension ROM. We found a significant moderate and negative relationship between shoulder extension ROM and PMc stiffness at long muscle length (rs = -0.33; p = 0.04) but not at short muscle length (r = -0.23; p = 0.17). Additionally, there was no significant difference between male and female participants in the correlation analyses at both elbow angles. The moderate correlation between PMc stiffness at a slightly stretched position and shoulder extension ROM suggests that additionally, other structures such as nerves/fascia stiffness or even stretch tolerance might be factors that can be related to shoulder extension ROM.

12.
NPJ Microgravity ; 10(1): 41, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38548798

RESUMO

The cardiovascular system is strongly impacted by the hazards of spaceflight. Astronauts spending steadily increasing lengths of time in microgravity are subject to cardiovascular deconditioning resulting in loss of vascular tone, reduced total blood volume, and diminished cardiac output. Appreciating the mechanisms by which the cells of the vasculature are altered during spaceflight will be integral to understanding and combating these deleterious effects as the human presence in space advances. In this study, we performed RNA-Seq analysis coupled with review by QIAGEN Ingenuity Pathway Analysis software on human aortic smooth muscle cells (HASMCs) cultured for 3 days in microgravity and aboard the International Space Station to assess the transcriptomic changes that occur during spaceflight. The results of our RNA-Seq analysis show that SMCs undergo a wide range of transcriptional alteration while in space, significantly affecting 4422 genes. SMCs largely down-regulate markers of the contractile, synthetic, and osteogenic phenotypes including smooth muscle alpha actin (αSMA), matrix metalloproteinases (MMPs), and bone morphogenic proteins (BMPs). Additionally, components of several cellular signaling pathways were strongly impacted including the STAT3, NFκB, PI3K/AKT, HIF1α, and Endothelin pathways. This study highlights the significant changes in transcriptional behavior SMCs exhibit during spaceflight and puts these changes in context to better understand vascular function in space.

13.
Int Immunopharmacol ; 130: 111709, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38377857

RESUMO

Methotrexate (MTX), a chemotherapeutic antimetabolite, has been linked to cognitive impairment in cancer patients. MTX-induced metabolic pathway disruption may result in decreased antioxidant activity and increased oxidative stress, influencing hippocampal neurogenesis and microglial activation. Nuclear factor-kappa B (NF-κB), an oxidative stress byproduct, has been linked to MTX toxicity via the activation of NLRP3 inflammasome signaling. Macrophage activation and polarization plays an important role in tissue injury. This differentiation may be mediated via either the Toll-like receptor 4 (TLR4) or NLRP3 inflammasome. Interestingly, Canagliflozin (CANA), a sodium-glucose cotransporter 2 (SGLT2) inhibitor has been recently reported to exert anti-inflammatory effects by modulating macrophage polarization balance. This study aimed to investigate CANA's protective effect against MTX-induced cognitive impairment, highlighting the possible involvement of TLR4/ NF-κB crosstalk with NLRP3 inflammasome activation and macrophage polarization. Forty-eight Male Wistar rats were divided into 4 groups; (1) received saline orally for 30 days and intravenously on days 8 and 15. (2) received Canagliflozin (CANA; 20 mg/kg/day; p.o.) for 30 days. (3) received MTX (75 mg/kg, i.v.) on day 8 and 15, then they were injected with four i.p. injections of leucovorin (LCV): the first dose was 6 mg/ kg after 18 h, and the remaining doses were 3 mg/kg after 26, 42, and 50 h of MTX administration. (4) received MTX and LCV as in group 3 in addition to CANA as in group 2. MTX-treated rats showed cognitive deficits in spatial and learning memory as evidenced in the novel object recognition and Morris water maze tests. MTX exerted an oxidative effect which was evident by the increase in MDA and decline in SOD, GSH and GPx. Moreover, it exerted an inflammatory effect via elevated caspase-1, IL-1ß and IL-8. CANA treatment restored cognitive ability, reduced MTX-induced oxidative stress and neuroinflammation via attenuation of TLR4/NF-κB/NLRP3 signaling, and rebalanced macrophage polarization by promoting the M2 phenotype. Hence, targeting molecular mechanisms manipulating macrophage polarization may offer novel neuroprotective strategies for preventing or treating MTX-induced immune modulation and its detrimental sequel.


Assuntos
Disfunção Cognitiva , Fármacos Neuroprotetores , Humanos , Masculino , Ratos , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Metotrexato/toxicidade , NF-kappa B/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Receptor 4 Toll-Like/metabolismo , Canagliflozina , Ratos Wistar , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Macrófagos/metabolismo
14.
Am J Med Genet A ; 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38407483

RESUMO

Genetic testing for germline RET pathogenic variants, which cause the Multiple Endocrine Neoplasia Type 2 (MEN2) syndrome, has become crucial in managing patients with medullary thyroid carcinoma (MTC). Classically, RET heterozygous missense pathogenic variants are transmitted in a Mendelian autosomal dominant pattern, of which germline/gonadal mosaicism has never been reported. We report the novel occurrence of a MEN2A patient's family in which the siblings inherited three different RET 634 genotypes: wild type (p.Cys634), p.Cys634Gly or p.Cys634Arg heterozygous pathogenic variants. We hypothesized that germline/gonadal mosaicism, derived from an inherited + early somatic mutation in the mother or a double de novo mutation during maternal embryogenesis, led to this rare event in the RET gene. Exome analysis of the proband's deceased mother's paraffin-embedded thyroid tissue confirmed the three nucleotides in the same 634 codon position. For the first time, we describe germline/gonadal mosaicism in RET, generating a second pathogenic amino acid change in the same codon causing MEN2A. Our finding shows that RET parental mosaicism, confirmed by somatic exome sequencing, might explain discrepant genotype cases in siblings with inherited cancers.

15.
Water Sci Technol ; 89(3): 788-798, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38358502

RESUMO

Antimony, extensively used in energy applications, poses toxicity and contamination concerns, especially in anaerobic environments where its impact on microbial activity is poorly understood. Emerging remedies, like biochar, show promise in soil and water treatment. This study investigates biochar's influence on methanogenic activity under Sb(V) and Sb(III) stress using anaerobic sludge as inoculum and lactate as the carbon source. Sb(III) and Sb(V) were introduced at varied concentrations (5-80 mg/L), with or without biochar, monitoring changes in biogas production, pH, Sb, and lactate levels over time. Experiments with Sb(V) also involved calculating mass balance and electron distribution. Results showcased the following significant enhancements: biochar notably improved COD removal and biogas production in Sb(III) spiked conditions, up to 5-fold and 2-fold increases, respectively. Sb(III) removal reached up to 99% with biochar, while in high Sb(V) concentrations, biochar reduced the adverse effect on biogas production by 96%. Adsorption capacities favored biomass (60.96 mg Sb(III)/gVSS, and 22.4 mg Sb(V)/gVSS) over biochar (3.33 mg Sb(III)/g, and 1.61 mg Sb(V)/g) for both Sb species. This study underscores biochar's potential to mitigate metalloid impact on methanogenic activity while aiding Sb removal from liquid phase, suggesting promising implications for remediation and methane production enhancement strategies.


Assuntos
Antimônio , Carvão Vegetal , Euryarchaeota , Biocombustíveis , Ácido Láctico , Metano
16.
Ann Biomed Eng ; 52(4): 1021-1038, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38294641

RESUMO

Traumatic brain injury (TBI) is the leading cause of accident-related death and disability in the world and can lead to long-term neuropsychiatric symptoms, such as a decline in cognitive function and neurodegeneration. TBI includes primary and secondary injury, with head trauma and deformation of the brain caused by the physical force of the impact as primary injury, and cellular and molecular cascades that lead to cell death as secondary injury. Currently, there is no treatment for TBI-induced cell damage and neural circuit dysfunction in the brain, and thus, it is important to understand the underlying cellular mechanisms that lead to cell damage. In the current study, we use stretchable microelectrode arrays (sMEAs) to model the primary injury of TBI to study the electrophysiological effects of physically injuring cortical cells. We recorded electrophysiological activity before injury and then stretched the flexible membrane of the sMEAs to injure the cells to varying degrees. At 1, 24, and 72 h post-stretch, we recorded activity to analyze differences in spike rate, Fano factor, burstlet rate, burstlet width, synchrony of firing, local network efficiency, and Q statistic. Our results demonstrate that mechanical injury changes the firing properties of cortical neuron networks in culture in a time- and severity-dependent manner. Our results suggest that changes to electrophysiological properties after stretch are dependent on the strength of synchronization between neurons prior to injury.


Assuntos
Lesões Encefálicas Traumáticas , Lesões Encefálicas , Humanos , Neurônios/fisiologia , Encéfalo
17.
Plants (Basel) ; 13(2)2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38256737

RESUMO

The andromonoecy is an unusual sex expression in trees in which an individual plant bears both functionally staminate and hermaphrodite flowers on the inflorescences. This study aims to investigate the effect of crown layers on the floral biology and reproductive effort of Aesculus indica (Wall. ex Camb.) Hook. The results revealed that the peak period of anthesis was between 06:00 and 08:00 h of the day. Male flower production was predominantly higher as compared to the perfect flowers on the inflorescences. There was no significant variation between total pollen production in staminate and perfect flowers. Features like protogyny and inter-level asynchrony promote xenogamy; however, intra-level asynchrony results in geitonogamy. Controlled pollination treatments revealed the existence of self-incompatibility in flowers. Pollination syndromes in flowers support ambophily. A trend of consistent improvement in reproductive success from lower canopy layers to upper crown layers in the analyzed trees was recorded. The crown layers have a significant impact on flower production, fruit, and seed set. An increase in male flower production due to the increment in the crown is a mechanism of reproductive assurance as a pollen donor and pollinator recipient and also due to the differential cost of expenditure of reproduction in crown layers. Andromonoecy in A. indica promotes self-incompatibility, and there was a tapering trend of reproductive success in the crown layers.

18.
Cell Biosci ; 14(1): 3, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38178246

RESUMO

BACKGROUND: The absence of expression of the Y-chromosome linked testis-determining gene SRY in early supporting gonadal cells (ESGC) leads bipotential gonads into ovarian development. However, genetic variants in NR2F2, encoding three isoforms of the transcription factor COUP-TFII, represent a novel cause of SRY-negative 46,XX testicular/ovotesticular differences of sex development (T/OT-DSD). Thus, we hypothesized that COUP-TFII is part of the ovarian developmental network. COUP-TFII is known to be expressed in interstitial/mesenchymal cells giving rise to steroidogenic cells in fetal gonads, however its expression and function in ESGCs have yet to be explored. RESULTS: By differentiating induced pluripotent stem cells into bipotential gonad-like cells in vitro and by analyzing single cell RNA-sequencing datasets of human fetal gonads, we identified that NR2F2 expression is highly upregulated during bipotential gonad development along with markers of bipotential state. NR2F2 expression was detected in early cell populations that precede the steroidogenic cell emergence and that retain a multipotent state in the undifferentiated gonad. The ESGCs differentiating into fetal Sertoli cells lost NR2F2 expression, whereas pre-granulosa cells remained NR2F2-positive. When examining the NR2F2 transcript variants individually, we demonstrated that the canonical isoform A, disrupted by frameshift variants previously reported in 46,XX T/OT-DSD patients, is nearly 1000-fold more highly expressed than other isoforms in bipotential gonad-like cells. To investigate the genetic network under COUP-TFII regulation in human gonadal cell context, we generated a NR2F2 knockout (KO) in the human granulosa-like cell line COV434 and studied NR2F2-KO COV434 cell transcriptome. NR2F2 ablation downregulated markers of ESGC and pre-granulosa cells. NR2F2-KO COV434 cells lost the enrichment for female-supporting gonadal progenitor and acquired gene signatures more similar to gonadal interstitial cells. CONCLUSIONS: Our findings suggest that COUP-TFII has a role in maintaining a multipotent state necessary for commitment to the ovarian development. We propose that COUP-TFII regulates cell fate during gonad development and impairment of its function may disrupt the transcriptional plasticity of ESGCs. During early gonad development, disruption of ESGC plasticity may drive them into commitment to the testicular pathway, as observed in 46,XX OT-DSD patients with NR2F2 haploinsufficiency.

19.
Eur J Obstet Gynecol Reprod Biol ; 294: 84-91, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38219608

RESUMO

OBJECTIVE: Polycystic ovary syndrome (PCOS) is an endocrinopathy with a high prevalence in women of reproductive age. Different treatments were tested to increase insulin sensitivity and hormone regulation, and recently polyphenols have emerged as a promising option for these women. We aimed to perform a systematic review and meta-analysis of randomized clinical trials (RCTs) comparing polyphenols to placebo in PCOS. DESIGN: A systematic review and meta-analysis. METHODS: PubMed, Cochrane Library, and Embase databases were searched for RCTs comparing polyphenols to placebo. Random-effects model was used to calculate the Mean Difference (MD) and Standardized Mean Difference (SMD), with 95% confidence interval (CIs). RESULTS: A total of fifteen RCTs comprising 916 patients were included, of whom 445 (49 %) received polyphenols. Compared to placebo, polyphenols significantly reduced serum insulin level (MD -2.49; 95 % CI [-3.72, -1.25]; p < 0.01), BMI levels (MD -0.12; 95 % CI [-0.18, -0.06]; p < 0.01), and LH levels (MD -0.87; 95 % CI [-1.54, -0.20]; p = 0.01). There was no significant difference between groups in testosterone levels (SMD -0.14; 95 % CI [-0.53, 0.25]; p = 0.48). CONCLUSION: In this meta-analysis polyphenols were associated with a reduction in serum insulin, LH levels, and BMI in women with PCOS, compared to placebo. These findings support the effectiveness of polyphenols in women with PCOS. SIGNIFICANT STATEMENT: There are no comprehensive systematic recommendations for polyphenols in PCOS treatment. However, increasing evidence has highlighted its substantial impact on women's health. This systematic review and meta-analysis provide evidence for the efficacy of polyphenols in reducing serum insulin, LH, and BMI in women with PCOS compared with placebo.


Assuntos
Resistência à Insulina , Insulinas , Síndrome do Ovário Policístico , Feminino , Humanos , Síndrome do Ovário Policístico/complicações , Ensaios Clínicos Controlados Aleatórios como Assunto , Resistência à Insulina/fisiologia , Saúde da Mulher , Insulinas/uso terapêutico
20.
Pediatr Transplant ; 28(1): e14646, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37975173

RESUMO

BACKGROUND: Right versus left kidney donor nephrectomy remains a controversial topic in renal transplantation given the increased incidence of right kidney vascular anomalies and associated venous thrombosis. We present the case of a 3-year-old pediatric recipient with urethral atresia and end-stage kidney disease who received a robotically procured living donor right pelvic kidney with two short same-size renal veins and a short ureter. METHODS: We utilized a completely deceased iliac vein system (common iliac vein with both external and internal veins) to extend the two renal veins. Due to the distance between both renal veins, the external iliac vein was anastomosed to the upper hilum renal vein, and the internal iliac vein was anastomosed to the lower hilum renal vein. The donor's short ureter was anastomosed to the recipient's ureter end-to-side. RESULTS: The patient had immediate graft function and there were no post-operative complications. Renal ultrasound was unremarkable at 48 hours post-transplant. Serum creatinine was 0.5 mg/dL at 3 months post-transplant. CONCLUSION: We demonstrate the successful transplantation of a robotically procured right pelvic donor kidney with two short renal veins using a deceased donor iliac vein system for venous reconstruction without increasing technical complications. This technique of venous reconstruction can be used in right kidneys with similar anatomical variations without affecting graft function.


Assuntos
Transplante de Rim , Veias Renais , Humanos , Criança , Pré-Escolar , Veias Renais/cirurgia , Rim/cirurgia , Rim/irrigação sanguínea , Procedimentos Cirúrgicos Vasculares/métodos , Transplante de Rim/métodos , Veia Cava Inferior , Doadores Vivos
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