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1.
Nano Lett ; 24(25): 7623-7628, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38860722

RESUMO

Hexagonal boron nitride (h-BN) hosts pure single-photon emitters that have shown evidence of optically detected electronic spin dynamics. However, the electrical and chemical structures of these optically addressable spins are unknown, and the nature of their spin-optical interactions remains mysterious. Here, we use time-domain optical and microwave experiments to characterize a single emitter in h-BN exhibiting room temperature optically detected magnetic resonance. Using dynamical simulations, we constrain and quantify transition rates in the model, and we design optical control protocols that optimize the signal-to-noise ratio for spin readout. This constitutes a necessary step toward quantum control of spin states in h-BN.

2.
Glia ; 72(4): 748-758, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38200694

RESUMO

Implantable neural probes have been extensively utilized in the fields of neurocircuitry, systems neuroscience, and brain-computer interface. However, the long-term functionality of these devices is hampered by the formation of glial scar and astrogliosis at the surface of electrodes. In this study, we administered KDS2010, a recently developed reversible MAO-B inhibitor, to mice through ad libitum drinking in order to prevent glial scar formation and astrogliosis. The administration of KDS2010 allowed long-term recordings of neural signals with implantable devices, which remained stable over a period of 6 months and even restored diminished neural signals after probe implantation. KDS2010 effectively prevented the formation of glial scar, which consists of reactive astrocytes and activated microglia around the implant. Furthermore, it restored neural activity by disinhibiting astrocytic MAO-B dependent tonic GABA inhibition induced by astrogliosis. We suggest that the use of KDS2010 is a promising approach to prevent glial scar formation around the implant, thereby enabling long-term functionality of neural devices.


Assuntos
Astrócitos , Gliose , Camundongos , Animais , Gliose/tratamento farmacológico , Gliose/prevenção & controle , Inibidores da Monoaminoxidase/farmacologia , Monoaminoxidase/farmacologia , Macrófagos
3.
Glia ; 72(9): 1707-1724, 2024 09.
Artigo em Inglês | MEDLINE | ID: mdl-38864289

RESUMO

Astrocytes play an essential role in regulating synaptic transmission. This study describes a novel form of modulation of excitatory synaptic transmission in the mouse hippocampus by astrocytic G-protein-coupled receptors (GPCRs). We have previously described astrocytic glutamate release via protease-activated receptor-1 (PAR1) activation, although the regulatory mechanisms for this are complex. Through electrophysiological analysis and modeling, we discovered that PAR1 activation consistently increases the concentration and duration of glutamate in the synaptic cleft. This effect was not due to changes in the presynaptic glutamate release or alteration in glutamate transporter expression. However, blocking group II metabotropic glutamate receptors (mGluR2/3) abolished PAR1-mediated regulation of synaptic glutamate concentration, suggesting a role for this GPCR in mediating the effects of PAR1 activation on glutamate release. Furthermore, activation of mGluR2/3 causes glutamate release through the TREK-1 channel in hippocampal astrocytes. These data show that astrocytic GPCRs engage in a novel regulatory mechanism to shape the time course of synaptically-released glutamate in excitatory synapses of the hippocampus.


Assuntos
Astrócitos , Região CA1 Hipocampal , Ácido Glutâmico , Camundongos Endogâmicos C57BL , Receptor PAR-1 , Receptores de Glutamato Metabotrópico , Sinapses , Animais , Receptores de Glutamato Metabotrópico/metabolismo , Astrócitos/metabolismo , Ácido Glutâmico/metabolismo , Sinapses/metabolismo , Região CA1 Hipocampal/metabolismo , Receptor PAR-1/metabolismo , Camundongos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Masculino , Transmissão Sináptica/fisiologia , Transmissão Sináptica/efeitos dos fármacos , Canais de Potássio de Domínios Poros em Tandem/metabolismo
4.
J Am Chem Soc ; 146(8): 5702-5711, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38372651

RESUMO

Macrocycles and medium-sized rings are important in many scientific fields and technologies but are hard to make using current methods, especially on a large scale. Outlined herein is a strategy by which functionalized macrocycles and medium-sized rings can be prepared using cyclization/ring expansion (CRE) cascade reactions, without resorting to high dilution conditions. CRE cascade reactions are designed to operate exclusively via kinetically favorable 5-7-membered ring cyclization steps; this means that the problems typically associated with classical end-to-end macrocyclization reactions are avoided. A modular synthetic approach has been developed to facilitate the simple assembly of the requisite linear precursors, which can then be converted into an extremely broad range of functionalized macrocycles and medium-sized rings using one of nine CRE protocols.

5.
Ann Oncol ; 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39098455

RESUMO

BACKGROUND: Nivolumab+ipilimumab (NIVO+IPI) has demonstrated superior overall survival (OS) and durable response benefits versus sunitinib (SUN) with long-term follow-up in patients with advanced renal cell carcinoma (aRCC). We report updated analyses with 8 years median follow-up from CheckMate 214. PATIENTS AND METHODS: Patients with aRCC (N=1096) were randomized to NIVO 3 mg/kg plus IPI 1 mg/kg Q3W × four doses, followed by NIVO (3 mg/kg or 240 mg Q2W or 480 mg Q4W); or SUN (50 mg) once daily for 4 weeks on, 2 weeks off. Endpoints included OS, and independent radiology review committee-assessed progression-free survival (PFS) and objective response rate (ORR) in intermediate/poor-risk (I/P; primary), intent-to-treat (ITT; secondary), and favorable-risk (FAV; exploratory) patients. RESULTS: With 8 years (99.1 months) median follow-up, the HR (95% CI) for OS with NIVO+IPI versus SUN was 0.72 (0.62-0.83) in ITT patients, 0.69 (0.59-0.81) in I/P patients, and 0.82 (0.60-1.13) in FAV patients. PFS probabilities at 90 months were 22.8% versus 10.8% (ITT), 25.4% versus 8.5% (I/P), and 12.7% versus 17.0% (FAV), respectively. ORR with NIVO+IPI versus SUN was 39.5% versus 33.0% (ITT), 42.4% versus 27.5% (I/P), and 29.6% versus 51.6% (FAV). Rates of complete response were higher with NIVO+IPI versus SUN in all IMDC risk groups (ITT, 12.0% versus 3.5%; I/P, 11.8% versus 2.6%; FAV, 12.8% versus 6.5%). Median duration of response (95% CI) with NIVO+IPI versus SUN was 76.2 versus 25.1 months [59.1-not estimable (NE) versus 19.8-33.2; ITT], 82.8 versus 19.8 months [54.1-NE versus 16.4-26.4; I/P], and 61.5 versus 33.2 months [27.8-NE versus 24.8-51.4; FAV]). Incidence of treatment-related adverse events was consistent with previous reports. Exploratory post hoc analyses are reported for FAV patients, those receiving subsequent therapy based on their response status, clinical subpopulations, and adverse events over time. CONCLUSIONS: Superior survival, durable response benefits, and a manageable safety profile were maintained with NIVO+IPI versus SUN at 8 years, the longest phase III follow-up for a first-line checkpoint inhibitor combination therapy in aRCC.

6.
Magn Reson Med ; 92(3): 1248-1262, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38733066

RESUMO

PURPOSE: To present and assess an outlier mitigation method that makes free-running volumetric cardiovascular MRI (CMR) more robust to motion. METHODS: The proposed method, called compressive recovery with outlier rejection (CORe), models outliers in the measured data as an additive auxiliary variable. We enforce MR physics-guided group sparsity on the auxiliary variable, and jointly estimate it along with the image using an iterative algorithm. For evaluation, CORe is first compared to traditional compressed sensing (CS), robust regression (RR), and an existing outlier rejection method using two simulation studies. Then, CORe is compared to CS using seven three-dimensional (3D) cine, 12 rest four-dimensional (4D) flow, and eight stress 4D flow imaging datasets. RESULTS: Our simulation studies show that CORe outperforms CS, RR, and the existing outlier rejection method in terms of normalized mean square error and structural similarity index across 55 different realizations. The expert reader evaluation of 3D cine images demonstrates that CORe is more effective in suppressing artifacts while maintaining or improving image sharpness. Finally, 4D flow images show that CORe yields more reliable and consistent flow measurements, especially in the presence of involuntary subject motion or exercise stress. CONCLUSION: An outlier rejection method is presented and tested using simulated and measured data. This method can help suppress motion artifacts in a wide range of free-running CMR applications.


Assuntos
Algoritmos , Imageamento Tridimensional , Imagem Cinética por Ressonância Magnética , Humanos , Imageamento Tridimensional/métodos , Imagem Cinética por Ressonância Magnética/métodos , Artefatos , Simulação por Computador , Movimento (Física) , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Interpretação de Imagem Assistida por Computador/métodos , Reprodutibilidade dos Testes , Coração/diagnóstico por imagem
7.
J Urol ; : 101097JU0000000000004188, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39088547

RESUMO

INTRODUCTION AND OBJECTIVES: Several factors influence recurrence after urethral stricture repair. The impact of socioeconomic factors on stricture recurrence after urethroplasty is poorly understood. This study aims to assess the impact that social deprivation, an area-level measure of disadvantage, has on urethral stricture recurrence after urethroplasty. METHODS: We performed a retrospective review of patients undergoing urethral reconstruction by surgeons participating in a collaborative research group. Home zip code was used to calculate Social Deprivation Indices (SDI; 0-100), which quantifies the level of disadvantage across several sociodemographic domains collected in the American Community Survey. Patients without zip code data were excluded from the analysis. The Cox Proportional Hazards model was used to study the association between SDI and the hazard of functional recurrence, adjusting for stricture characteristics as well as age and body mass index. RESULTS: Median age was 46.0 years with a median follow up of 367 days for the 1452 men included in the study. Patients in the fourth SDI quartile (worst social deprivation) were more likely to be active smokers with traumatic and infectious strictures compared to the first SDI quartile. Patients in the fourth SDI quartile had 1.64 times the unadjusted hazard of functional stricture recurrence vs patients in the first SDI quartile (95% CI 1.04-2.59). Compared to anastomotic ± excision, substitution only repair had 1.90 times the unadjusted hazard of recurrence. The adjusted hazard of recurrence was 1.08 per 10-point increase in SDI (95% CI 1.01-1.15, P = .027). CONCLUSIONS: Patient social deprivation identifies those at higher risk for functional recurrence after anterior urethral stricture repair, offering an opportunity for preoperative counseling and postoperative surveillance. Addressing these social determinants of health can potentially improve outcomes in reconstructive surgery.

8.
J Neurooncol ; 166(3): 493-501, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38285244

RESUMO

BACKGROUND: Pharmacological ascorbate (intravenous delivery reaching plasma concentrations ≈ 20 mM; P-AscH-) has emerged as a promising therapeutic strategy for glioblastoma. Recently, a single-arm phase 2 clinical trial demonstrated a significant increase in overall survival when P-AscH- was combined with temozolomide and radiotherapy. As P-AscH- relies on iron-dependent mechanisms, this study aimed to assess the predictive potential of both molecular and imaging-based iron-related markers to enhance the personalization of P-AscH- therapy in glioblastoma participants. METHODS: Participants (n = 55) with newly diagnosed glioblastoma were enrolled in a phase 2 clinical trial conducted at the University of Iowa (NCT02344355). Tumor samples obtained during surgical resection were processed and stained for transferrin receptor and ferritin heavy chain expression. A blinded pathologist performed pathological assessment. Quantitative susceptibility mapping (QSM) measures were obtained from pre-radiotherapy MRI scans following maximal safe surgical resection. Circulating blood iron panels were evaluated prior to therapy through the University of Iowa Diagnostic Laboratory. RESULTS: Through univariate analysis, a significant inverse association was observed between tumor transferrin receptor expression and overall and progression-free survival. QSM measures exhibited a significant, positive association with progression-free survival. Subjects were actively followed until disease progression and then were followed through chart review or clinical visits for overall survival. CONCLUSIONS: This study analyzes iron-related biomarkers in the context of P-AscH- therapy for glioblastoma. Integrating molecular, systemic, and imaging-based markers offers a multifaceted approach to tailoring treatment strategies, thereby contributing to improved patient outcomes and advancing the field of glioblastoma therapy.


HIGHLIGHTS: Pharmacological ascorbate shows significant promise to enhance glioblastoma clinical outcomes. Transferrin receptor and ferritin heavy chain expression represent potential molecular markers to predict pharmacological ascorbate treatment response. Quantitative Susceptibility Mapping is an MRI technique that can serve as a non-invasive marker of iron metabolism to evaluate progression-free survival. Systemic iron metabolic markers are readily available diagnostic tests that can potentially be used to prognosticate overall survival.


Assuntos
Antineoplásicos , Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/diagnóstico por imagem , Glioblastoma/tratamento farmacológico , Ferro , Temozolomida/uso terapêutico , Antineoplásicos/uso terapêutico , Biomarcadores , Receptores da Transferrina , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/cirurgia
9.
World J Urol ; 42(1): 172, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38506927

RESUMO

PURPOSE: To compare the outcomes of patients undergoing robotic YV plasty for bladder neck contracture (BNC) vs. vesico-urethral anastomotic stricture (VUAS). METHODS: A retrospective study included male patients who underwent robotic YV plasty for BNC after endoscopic treatment of BPH or VUAS between August 2019 and March 2023 at a single academic center. The primary assessed was the patency rate at 1 month post-YV plasty and during the last follow-up visit. RESULTS: A total of 21 patients were analyzed, comprising 6 in the VUAS group and 15 in the BNC group. Patients with VUAS had significantly longer operative times (277.5 vs. 146.7 min; p = 0.008) and hospital stay (3.2 vs. 1.7 days; p = 0.03). Postoperative complications were more common in the VUAS group (66.7% vs. 26.7%; p = 0.14). All patients resumed spontaneous voiding postoperatively. Five patients (23.8%) who developed de novo stress urinary incontinence had already an AUS (n = 1) or required concomitant AUS implantation (n = 3), all of whom were in the VUAS group (83.3% vs. 0%; p < 0.0001). The proportion of patients improved was similar in both groups (PGII = 1 or 2: 83.3% vs. 80%; p = 0.31). Stricture recurrence occurred in 9.5% of patients in the whole cohort, with no significant difference between the groups (p = 0.50). Long-term reoperation was required in three VUAS patients, showing a statistically significant difference between the groups (p = 0.05). CONCLUSION: Robotic YV plasty is feasible for both VUAS and BNC. While functional outcomes and stricture-free survival may be similar for both conditions, the perioperative outcomes were less favorable for VUAS patients.


Assuntos
Contratura , Procedimentos Cirúrgicos Robóticos , Estreitamento Uretral , Obstrução do Colo da Bexiga Urinária , Humanos , Masculino , Bexiga Urinária/cirurgia , Constrição Patológica/etiologia , Constrição Patológica/cirurgia , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Estudos Retrospectivos , Obstrução do Colo da Bexiga Urinária/cirurgia , Obstrução do Colo da Bexiga Urinária/complicações , Contratura/cirurgia , Estreitamento Uretral/etiologia , Estreitamento Uretral/cirurgia , Prostatectomia/efeitos adversos
10.
Wound Repair Regen ; 32(4): 377-383, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38419162

RESUMO

The aim was to investigate methicillin-resistant Staphylococcus aureus (MRSA) incidence, conversion and outcomes in diabetic foot infections (DFIs). This is a pooled patient-level analysis of combined data sets from two randomised clinical trials including 219 patients admitted to the hospital with moderate or severe DFIs. Intraoperative bone and tissue cultures identified bacterial pathogens. We identified pathogens at index infections and subsequent re-infections. We identified MRSA conversion (MSSA to MRSA) in re-infections. MRSA incidence in index infections was 10.5%, with no difference between soft tissue infections (STIs) and osteomyelitis (OM). MRSA conversion occurred in 7.7% of the re-infections in patients who initially had MSSA in their cultures. Patients with re-infection were 2.2 times more likely to have MRSA compared to the first infection (10.5% vs. 25.8%, relative risk [RR] = 2.2, p = 0.001). Patients with MRSA had longer antibiotic treatment during the 1-year follow-up, compared to other pathogens (other 49.8 ± 34.7 days, MRSA 65.3 ± 41.5 days, p = 0.04). Furthermore, there were no differences in healing, time to heal, length of stay, re-infection, amputation, re-ulceration, re-admission, surgery after discharge and amputation after discharge compared to other pathogens. The incidence of MRSA at the index was 10.5% with no difference in STI and OM. MRSA incidence was 25.8% in re-infections. The RR of having MRSA was 2.2 times higher in re-infections. Patients with MRSA used more antibiotics during the 1-year follow-up. Furthermore, there were no differences in clinical outcomes compared to other bacterial pathogens.


Assuntos
Antibacterianos , Pé Diabético , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Pé Diabético/microbiologia , Pé Diabético/epidemiologia , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Antibacterianos/uso terapêutico , Idoso , Reinfecção/microbiologia , Incidência , Osteomielite/microbiologia , Osteomielite/epidemiologia , Amputação Cirúrgica/estatística & dados numéricos , Infecções dos Tecidos Moles/microbiologia , Infecções dos Tecidos Moles/terapia , Infecções dos Tecidos Moles/epidemiologia , Cicatrização , Resultado do Tratamento
11.
J Drugs Dermatol ; 23(2): 61-66, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38306139

RESUMO

INTRODUCTION: Chronic venous insufficiency (CVI) may lead to sustained elevated pressure (aka venous hypertension) in the dermal venous microcirculation. Risk factors include advanced age, obesity, female gender, pregnancy, and prolonged standing. CVI in the lower extremities may lead to cutaneous changes such as xerosis and venous leg dermatitis (VLD). This review explores skin barrier restoration using skincare for xerosis and VLD.    Methods: Prior to the meeting, a structured literature search yielded information on fourteen draft statements. During the meeting, a multi-disciplinary group of experts adopted five statements on xerosis and VLD supported by the literature and the authors’ clinical expertise.   Results: VLD and associated xerosis is a common condition requiring more attention from healthcare providers. Compression therapy is the standard CVI and should be combined with good-quality skincare to enhance adherence to treatment. Maintaining an intact skin barrier by preventing and treating xerosis using gentle cleansers and ceramide-containing moisturizers may improve the skin sequelae of CVI. Skincare is frequently lacking or overlooked as part of the treatment of patients with CVI and VLD. This skin treatment is an unmet need that can be addressed with ceramides-containing pH balanced cleansers and moisturizers. CONCLUSION: Compression therapy is the mainstay of treatment for CVI and VLD. Quality skincare can improve treatment adherence and the efficacy of compression therapy. Using a skincare agent may reduce friction and help patients avoid skin trauma while putting on compression garments. A ceramide-containing moisturizer sustained significant improvements in skin moisturization for 24 hours and may offer synergistic benefits together with compression treatment.  J Drugs Dermatol. 2024;23(2):61-66.     doi:10.36849/JDD.7588.


Assuntos
Ceramidas , Dermatite , Insuficiência Venosa , Humanos , Ceramidas/uso terapêutico , Consenso , Perna (Membro) , Extremidade Inferior , Insuficiência Venosa/complicações , Insuficiência Venosa/terapia
12.
J Dairy Sci ; 107(9): 6717-6731, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38642660

RESUMO

An experiment was conducted to identify the factors that cause reduced production of cows fed a diet with high content of corn distillers grains with solubles (DDGS). We hypothesized that the factors could be high sulfur (S) content in DDGS, which may directly (S toxicity) or indirectly (DCAD) cause reduced production. We also hypothesized that high PUFA in DDGS could be another major factor. In a randomized complete block design, 60 lactating cows (15 primiparous and 45 multiparous; average ± SD at the beginning of the trial: milk yield, 44.0 ± 6.9 kg/d; DIM, 123 ± 50; BW, 672 ± 82 kg) were blocked, and cows in each block were randomly assigned to 1 of the following treatments: SBM (4.7% fatty acids [FA], 0.22% S, and 178 mEq/kg DM of DCAD), a diet containing soybean meal as the main protein source; DG, with SBM replacing mainly soybean byproducts and supplemental fat with distillers grains at 30% dietary DM (4.7% FA, 0.44% S, and 42 mEq/kg DM of DCAD); SBM+S, SBM with sodium bisulfate for additional dietary S (4.8% FA, 0.37% S, and 198 mEq/kg DM of DCAD); SBM+CO, SBM with corn oil (4.7% FA, 0.23%, and 165 mEq/kg DM of DCAD); and DG+DCAD, DG with increased DCAD (4.7% FA, 0.40% S, and 330 mEq/kg DM of DCAD). Due to the limited number of tiestalls, blocks 1 to 6 started the experiment first as phase 1, and the rest of the blocks, as phase 2, started the experiment after phase 1. All cows were fed the SBM diet for 10 d as a covariate period followed by the experimental period for 35 d. Data were analyzed using PROC MIXED of SAS (Version 9.4, SAS Institute Inc.); block and phase were random effects; and treatments, repeated week, and interaction were fixed effects. We found an interaction of week by treatment for DMI. Although milk yield did not change, milk fat concentration tended to decrease (2.78% vs. 3.34%) for DG compared with SBM. Dry matter, OM, NDF, and CP digestibilities were lower when cows were fed the DG diet compared with SBM. Additionally, cows fed DG had lower blood concentrations of HCO3-, base excess, and total (t)CO2 compared with SBM. The SBM+S diet did not affect production, nutrient digestibility, or blood parameters compared with SBM. The SBM+CO diet decreased milk fat concentration and yield compared with SBM. The DG+DCAD diet tended to increase milk fat yield and concentration (1.24 vs. 1.47 kg/d; 2.78% vs. 3.37%) and increased ECM (40.9 vs. 45.1 kg/d) compared with DG but did not improve nutrient digestibility. However, blood HCO3-, base excess, and tCO2 were greater for DG+DCAD compared with DG. In conclusion, the indirect role of S-, altering DCAD, along with the high PUFA content in DDGS, appear to be the factors causing reduced production responses to a high DDGS diet. Increasing DCAD to 300 mEq/kg DM in a high DDGS diet can be a feeding strategy to alleviate reduced production responses.


Assuntos
Ração Animal , Dieta , Lactação , Leite , Zea mays , Animais , Bovinos , Feminino , Dieta/veterinária , Leite/química , Ácidos Graxos
13.
J Dairy Sci ; 107(7): 4524-4536, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38395396

RESUMO

The objective of the experiment was to determine the effects of supplemental SFA sources, lysophospholipids (LPL), and their interaction on production and nutrient digestibility in lactating dairy cows. The experiment was conducted with 48 cows in a randomized complete block design. Cows were blocked (12 blocks total) by parity and days in milk and randomly assigned to 4 dietary treatments in each block (2 × 2 factorial arrangement), i.e., 2 sources of fat supplements, C16:0 (PA)- or C18:0 (SA)-enriched fat, and with or without LPL. The experiment was conducted for 6 wk to measure daily dry matter intake, milk yield, and weekly milk composition. During the last week of the experiment, spot fecal and urine samples were collected to determine total-tract nutrient digestibility. Milk samples in the last week were also collected to analyze the milk fatty acid (FA) profile. All data were analyzed using the MIXED procedure of SAS, where block was used as a random effect and FA, LPL, and the interaction of FA by LPL were used as fixed effects. Week and interactions of week by FA or LPL were included for production measures. Different sources of SFA did not affect dry matter intake and milk yield. However, the PA treatment increased (39.7 vs. 36.8 kg) energy-corrected milk compared with SA due to increased milk fat yield. No effect of LPL on production measures was observed. Total-tract digestibilities of dry matter, organic matter, crude protein, and total FA were not different between the PA and SA groups, but PA increased (41.4% vs. 38.8%) neutral detergent fiber digestibility compared with SA. Supplementation of LPL increased (64.7% vs. 60.5%) total FA digestibility, especially 18-carbon FA (74.1% vs. 68.2%). An interaction of SFA by LPL was found for 16-carbon FA digestibility. The PA diet increased the concentration of 16-carbon FA in milk fat and SA increased the concentration of preformed FA (≥18 carbons). Supplementation of LPL decreased the concentration of trans-10 C18:1. No difference in N utilization and excretion among treatments was observed. In conclusion, the PA diet was more effective in improving milk fat yield of lactating cows compared with SA. Supplementation of LPL increased digestibility of total FA, especially 18-carbon FA but did not affect production.


Assuntos
Dieta , Digestão , Ácidos Graxos , Lactação , Lisofosfolipídeos , Leite , Animais , Bovinos , Feminino , Leite/química , Leite/metabolismo , Dieta/veterinária , Lisofosfolipídeos/metabolismo , Digestão/efeitos dos fármacos , Ração Animal , Suplementos Nutricionais , Nutrientes/metabolismo
14.
J Dairy Sci ; 107(7): 4147-4160, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38490539

RESUMO

Human milk oligosaccharides (HMO) affect gut microbiota during neonatal development, particularly with respect to the immune system. Bovine milk-based infant formulas have low oligosaccharide contents. Thus, efforts to fortify infant formulas with HMO are being undertaken. Two major HMO, 2'-fucosyllactose (2'-FL) and 6'-sialyllactose (6'-SL), exert anti-inflammatory effects; however, the associations between anti-inflammatory effects induced by 2'-FL and 6'-SL cotreatment and gut microbiota composition and metabolite modulation remain unclear. Therefore, in this study, we evaluated the effects of a mixture of these HMO. To determine the optimal HMO ratio for anti-inflammatory effects and elucidate its mode of action, LPS-induced inflammatory HT-29 epithelial cells and intestinal-inflamed suckling mice were treated with various mixtures of 2'-FL and 6'-SL. A 2'-FL:6'-SL ratio of 5:1 was identified as the most effective pretreatment HMO mixture in vitro; thus, this ratio was selected and used for low-, middle-, and high-dose treatments for subsequent in vivo studies. In vivo, high-dose HMO treatment restored LPS-induced inflammation symptoms, such as BW loss, colon length reduction, histological structural damage, and intestinal gene expression related to inflammatory responses. High-dose HMO was the only treatment that modulated the major phyla Bacteroidetes and Firmicutes and the genera Ihubacter, Mageeibacillus, and Saccharofermentans. These changes in microbial composition were correlated with intestinal inflammation-related gene expression and short-chain fatty acid production. To our knowledge, our study is the first to report the effects of Ihubacter, Mageeibacillus, and Saccharofermentans on short-chain fatty acid levels, which can subsequently affect inflammatory cytokine and tight junction protein levels. Conclusively, the HMO mixture exerted anti-inflammatory effects through changes in microbiota and metabolite production. These findings suggest that supplementation of infant formula with HMO may benefit formula-fed infants by forming unique microbiota contributing to neonatal development.


Assuntos
Lipopolissacarídeos , Oligossacarídeos , Camundongos , Animais , Oligossacarídeos/farmacologia , Inflamação/tratamento farmacológico , Humanos , Microbioma Gastrointestinal/efeitos dos fármacos , Trissacarídeos/farmacologia , Lactose/análogos & derivados
15.
Ann Plast Surg ; 93(3): 355-360, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39150854

RESUMO

BACKGROUND: Often secondary to obesity, adult-acquired buried penis (AABP) is an increasingly common condition. AABP is often detrimental to urinary and sexual function, psychological well-being, and quality of life. Surgical treatment involves resection of excess soft tissue, with adjunct procedures, including a panniculectomy. However, few studies have been conducted investigating the risks of panniculectomy in the context of AABP surgical repair. METHODS: A systematic review of PubMed, Embase, and Cochrane databases was performed, following the PRISMA 2020 guidelines. Descriptive statistics regarding patient demographics, complications, and surgical technique were conducted. After this, an analysis of AABP patients within the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database was conducted. RESULTS: Four studies including 57 patients reported panniculectomy as part of buried penis repair (PBPR). Surgical approaches included a modified trapezoid and traditional transverse incision. All authors utilized postoperative drains. Dehiscence and wound infection were the most frequent complications. Univariate NSQIP analysis revealed that PBPR patients had higher body mass index, more comorbidities, and greater wound complication rates. Multivariate analysis revealed that PBPR did not significantly increase 30-day complications compared to isolated BPR ( P > 0.05), while body mass index remained a significant predictor. CONCLUSIONS: Surgical repair of AABP can greatly improve patient quality of life. The available literature and NSQIP-based analysis reveal that concurrent panniculectomy in AABP repair has a comparable complication profile. Future studies are necessary to better characterize the long-term outcomes of this PBPR.


Assuntos
Abdominoplastia , Humanos , Masculino , Abdominoplastia/métodos , Doenças do Pênis/cirurgia , Pênis/cirurgia , Pênis/anormalidades , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Bases de Dados Factuais , Adulto , Resultado do Tratamento
16.
Tech Coloproctol ; 28(1): 25, 2024 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-38231341

RESUMO

BACKGROUND: Total mesorectal excision using conventional straight fixed devices may be technically difficult because of the narrow and concave pelvis. Several laparoscopic articulating tools have been introduced as an alternative to robotic systems. The aim of this study was to compare perioperative outcomes between laparoscopic low anterior resection using ArtiSential® and robot-assisted surgery for rectal cancer. METHODS: This retrospective study included 682 patients who underwent laparoscopic or robotic low anterior resection  for rectal cancer from September 2018 to December 2021. Among them, 82 underwent laparoscopic surgery using ArtiSential® (group A) and 201 underwent robotic surgery (group B). A total of 73 [group A; 66.37 ± 11.62; group B 65.79 ± 11.34] patients were selected for each group using a propensity score matching analysis. RESULTS: There was no significant difference in the baseline characteristics between group A and B. Mean operative time was longer in group B than A (163.5 ± 61.9 vs 250.1 ± 77.6 min, p < 0.001). Mean length of hospital stay was not significantly different between the two groups (6.2 ± 4.7 vs 6.7 ± 6.1 days, p = 0.617). Postoperative complications, reoperation, and readmission within 30 days after surgery were similar between the two groups. Pathological findings revealed that the circumferential resection margins were above 10 mm in both groups (11.00 ± 7.47 vs 10.17 ± 6.25 mm, p = 0.960). At least 12 lymph nodes were sufficiently harvested, with no significant difference in the number harvested between the groups (20.5 ± 9.9 vs 19.7 ± 7.3, p = 0.753). CONCLUSIONS: Laparoscopic low anterior resection using ArtiSential® can achieve acceptable clinical and oncologic outcomes. ArtiSential®, a multi-joint and articulating device, may serve a feasible alternative approach to robotic surgery in rectal cancer.


Assuntos
Laparoscopia , Neoplasias Retais , Procedimentos Cirúrgicos Robóticos , Humanos , Pontuação de Propensão , Estudos Retrospectivos , Neoplasias Retais/cirurgia
17.
Hong Kong Med J ; 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39147587

RESUMO

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is becoming increasingly common among children and adolescents worldwide, including those in Hong Kong. This study analysed the characteristics and prevalence of microvascular complications among paediatric T2DM patients in Hong Kong at diagnosis and 2 years after diagnosis. METHODS: All patients aged <18 years who had been diagnosed with DM at public hospitals in Hong Kong were recruited into the Hong Kong Childhood Diabetes Registry. Data collected at diagnosis and 2 years after diagnosis were retrospectively retrieved from the Registry for patients diagnosed from 2014 to 2018. RESULTS: Median haemoglobin A1c (HbA1c) levels were 7.5% (n=203) at diagnosis and 6.5% (n=135) 2 years after diagnosis; 59.3% of patients achieved optimal glycaemic control (HbA1c level <7%) at 2 years. A higher HbA1c level at diagnosis was associated with worse glycaemic control at 2 years (correlation coefficient=0.39; P<0.001). The presence of dyslipidaemia (adjusted odds ratio [aOR]=3.19; P=0.033) and fatty liver (aOR=2.50; P=0.021) at 2 years were associated with suboptimal glycaemic control. Diabetic neuropathy and retinopathy were rare in our cohort, but 18.6% of patients developed microalbuminuria (MA) within 2 years after diagnosis. Patients with MA had a higher HbA1c level at 2 years (median: 7.2% vs 6.4%; P=0.037). Hypertension was a risk factor for MA at 2 years, independent of glycaemic control (aOR=4.61; P=0.008). CONCLUSION: These results highlight the importance of early diagnosis and holistic management (including co-morbidity management) for paediatric T2DM patients.

18.
New J Phys ; 26(2): 023006, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38327877

RESUMO

In interacting dynamical systems, specific local interaction rules for system components give rise to diverse and complex global dynamics. Long dynamical cycles are a key feature of many natural interacting systems, especially in biology. Examples of dynamical cycles range from circadian rhythms regulating sleep to cell cycles regulating reproductive behavior. Despite the crucial role of cycles in nature, the properties of network structure that give rise to cycles still need to be better understood. Here, we use a Boolean interaction network model to study the relationships between network structure and cyclic dynamics. We identify particular structural motifs that support cycles, and other motifs that suppress them. More generally, we show that the presence of dynamical reflection symmetry in the interaction network enhances cyclic behavior. In simulating an artificial evolutionary process, we find that motifs that break reflection symmetry are discarded. We further show that dynamical reflection symmetries are over-represented in Boolean models of natural biological systems. Altogether, our results demonstrate a link between symmetry and functionality for interacting dynamical systems, and they provide evidence for symmetry's causal role in evolving dynamical functionality.

19.
J Environ Manage ; 351: 119821, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38169265

RESUMO

Offshore wind development is in its nascent stages in the United States. Recent research indicates that the visual impacts of offshore wind farms are viewed negatively by the general population. This North Carolina application is the first US-focused discrete choice experiment that explicitly asks respondents to consider the positive local and global benefits from offshore wind development, such as job creation and greenhouse gas emission reductions, simultaneously with their visual impacts. We find significant willingness to pay (WTP) for reducing the visual impacts of offshore wind farms, and that the extent of disamenity varies in the population and with placement along developed tourist towns (as much as $783/year for three years) or preserved coastlines (as much as $451/year for three years). We also find that some preference classes value projects that create permanent jobs and reduce carbon emissions. We use our estimates of preferences for the positive and negative attributes to explore specific wind farm configurations and locations that could achieve positive consensus in a heterogenous population.


Assuntos
Fontes Geradoras de Energia , Vento , Humanos , Estados Unidos , North Carolina , Fazendas
20.
Med J Malaysia ; 79(4): 397-407, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39086336

RESUMO

INTRODUCTION: As climate change is threatening every region of the world, extreme weather events resultant of global warming is occurring at increasing rate and scale in Malaysia. Weather-related disasters such as flood and haze pose critical challenges to the infrastructure and raise public health concerns in the country, especially when main economic sectors rely heavily on climate variability. Public perception on environmental issues is crucial for development of pro-environmental policies. Among studies conducted to understand public awareness regarding global warming, reports of perception on the health impacts were very limited. Taking this limitation into account, this study was designed to examine the perception on the health impacts of climate change among the diverse communities living in the Johor River Basin. MATERIALS AND METHODS: The cross-sectional study was conducted through cloud-data-based digital questionnaires completed by randomly selected residents in the Johor River Basin (n=647). Data was analysed with descriptive statistics using SPSS 27 (IBM®) Software. Comparisons between indigenous and non-indigenous communities were performed using Chi square analysis. RESULTS: Respondents in this study consisted of indigenous people (n=79) and non-indigenous people (n=568). Indigenous respondents generally perceived more frequent occurrence of extreme weather events in the next 20 years, even for the phenomena unfamiliar in Malaysian settings. All respondents showed similar concerns for health impacts of global warming, although the non-indigenous respondents perceived the risk further into the future (25 years) compared to the indigenous respondents who perceived current or imminent (<10 years) risks. Intense concerns for self, children, family members and community were shown by nearly all indigenous respondents (97-99%), while the non-indigenous people in this study expressed stronger concerns at country level and for future generations. During the last haze episode, most indigenous respondents (85%) did not notice any change in air quality nor discomfort among family members, in contrast 70% of the nonindigenous respondents claimed to have suffered from breathing problems themselves as well as others in the family. All respondents were concerned about air quality in their surroundings, indigenous people were concerned for the near future (<10 years), and non-indigenous people were concerned for the next 25 years. CONCLUSION: In this study, respondents were generally concerned about the health impacts of unimpeded global warming. There was significant difference in perceptions between indigenous and non-indigenous respondents. The findings were useful, complemented with further studies, to improve understanding of public awareness and to help develop relevant education programmes accessible for wider audience.


Assuntos
Mudança Climática , Malásia , Humanos , Estudos Transversais , Masculino , Feminino , Adulto , Inquéritos e Questionários , Pessoa de Meia-Idade , Percepção
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