RESUMO
The concept of precision nutrition highlights the customization of nutrition to specific needs, emphasizing that a one-size-fits-all approach is not sufficient for either optimal nutrition or optimal health. Precision nutrition encompasses a range of factors, from broad strata of age and sex categories to personal characteristics such as lifestyle to an individual's unique genotype. This breadth of scope requires us to consider how precision nutrition can be implemented in an inclusive and appropriate way for individuals and groups within real-life populations. In this narrative review, we explore the potential of precision nutrition through a life-stage approach that emphasizes age- and gender-specific nutritional needs as these change across the lifespan. Focusing on adult life stages, we delineated trends in age-related conditions and health needs among Korean adults based on national-level survey data (KNHANES 2019-2021). We also reviewed the intake of nutrients associated with these health needs to better understand how life-stage guided approaches to nutrition and supplementation could support optimal health. Looking beyond preventing deficiency or disease, we discuss how tailored supplementation of essential vitamins, minerals, and certain bioactive substances could promote healthy functioning. Finally, we discuss the complexities and challenges of developing multivitamin/multimineral supplements (MVMS) to support life-stage appropriate nutrition while maximizing adherence. Future prospects include leveraging advancements in intelligent technologies and dietary assessments for tracking nutrient intake and health indicators and using these to optimize MVMS formulations in ways that are sensitive to a person's needs and priorities/preferences at different life stages. By adopting a life-stage guided approach to nutrition, we can better support health and well-being across the lifespan.
RESUMO
PURPOSE: This study aimed to evaluate the efficacy of local ablative therapy (LAT) combined with pembrolizumab in patients with synchronous oligometastatic non-small cell lung cancer (NSCLC) and to identify patients who would most benefit from LAT. METHODS AND MATERIALS: We retrospectively identified patients who received diagnosis of synchronous oligometastatic NSCLC (≤5 metastatic lesions and ≤3 organs involved) and were treated with first-line pembrolizumab between January 2017 and December 2022. Patients who underwent LAT, including surgery or radiation therapy at all disease sites, were compared with those who did not undergo LAT. A recursive partitioning analysis (RPA) model was developed using prognostic factors for progression-free survival (PFS). RESULTS: Among the 258 patients included, 78 received LAT with pembrolizumab, and 180 received pembrolizumab alone. The median follow-up duration was 15.5 months (range, 3.0-71.2 months). In the entire cohort, LAT was independently associated with significantly improved PFS (hazard ratio [HR], 0.64; P = .015) and overall survival (OS) (HR, 0.61; P = .020). In the propensity score-matched cohort (N = 74 in each group), the median PFS was 19.9 months and 9.6 months, respectively (P = .003), and the median OS was 42.2 months and 20.5 months, respectively (P = .045), for the LAT and non-LAT groups. Based on the RPA model, incorporating the number of metastatic lesions, performance status, and programmed cell death-ligand 1 expression level, patients were stratified into 3 risk groups with distinct PFS. LAT significantly improved PFS and OS in the low- and intermediate-risk groups; however, no difference was observed in the high-risk group. LAT was more effective as a consolidative treatment after pembrolizumab initiation than as an upfront therapy. CONCLUSIONS: LAT combined with pembrolizumab was associated with higher PFS and OS compared with pembrolizumab alone in selected patients with synchronous oligometastatic NSCLC. The RPA model could serve as a valuable clinical tool for identifying appropriate patients for LAT.
RESUMO
We examined whether there were differences in the presence of centrum semiovale-enlarged perivascular spaces (CSO-ePVS) and basal ganglia-ePVS (BG-ePVS) among patients with Alzheimer disease-related cognitive impairment (ADCI) based on their age of onset. Out of a total of 239 patients with cognitive impairment, 155 with positive amyloid-PET results were included. Among these, 43 had early-onset ADCI (EOADCI) and 112 had late-onset ADCI (LOADCI). Patients with LOADCI exhibited a higher prevalence of hypertension, lacunes, white matter hyperintensities, and BG-ePVS than those with EOADCI. BG-ePVS showed a significant correlation with age at the onset and the number of lacunes, whereas CSO-ePVS did not exhibit any association. The higher prevalence of BG-ePVS in patients with LOADCI might be attributable to vascular risk factors (hypertension) and cerebral small vessel disease (CSVD). These findings support the hypothesis that BG-ePVS is associated with CSVD and vascular risk factors, whereas CSO-ePVS is associated with cerebral amyloid angiopathy.
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , República da Coreia/epidemiologia , Masculino , Feminino , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/patologia , Disfunção Cognitiva/epidemiologia , Idoso , Idade de Início , Sistema Glinfático/patologia , Sistema Glinfático/diagnóstico por imagem , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Doenças de Pequenos Vasos Cerebrais/complicações , Doenças de Pequenos Vasos Cerebrais/patologia , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/epidemiologia , Fatores de RiscoRESUMO
Purpose: To evaluate the course of the cutaneous nerve regarding the first extensor compartment to determine whether the dorsal or volar approach is safer for local injection into the first extensor compartment guided by ultrasound. Methods: We dissected the radial side of the wrists from 28 cadavers (52 wrists). Four-points along the imaginary line were set: the styloid process and 1 cm, 2 cm, and 3 cm proximal to the styloid process. The numbers of superficial radial nerve (SRN) and lateral antebrachial cutaneous nerve (LACN) branches were counted, and distances from the imaginary line at these points and nerve diameters were recorded. Digital images were superimposed to observe overall distribution of cutaneous nerve. Results: There were means of 3.3 SRN and 0.9 LACN branches observed in each wrist. The mean number of both SRN and LACN branches was 2.3 on the dorsal side and 1.9 on the volar side. The superimposed images indicated that both the dorsal and volar sides comprised abundant cutaneous nerves and that their paths varied markedly between patients. However, we observed that larger nerves with meaningful diameters were more abundant on the dorsal than the volar side. Conclusion: There were similar numbers of cutaneous nerves on both the dorsal and volar sides; however, we observed greater abundance of thicker cutaneous nerves on the dorsal side, and these were closer to the reference line than on the volar side. This anatomical study suggests that the risk imposed to cutaneous nerves would therefore be reduced when injection on the volar side.
RESUMO
Background: We aimed to comprehensively investigate the prognostic value of pretreatment laboratory parameters in elderly patients with glioblastoma treated with temozolomide (TMZ)-based chemoradiation. Methods: Patients agedâ ≥â 65 years from 4 institutions with newly diagnosed IDH-wild-type glioblastoma who received radiotherapy (RT) with concurrent TMZ between 2006 and 2021 were included. Patient factors (age, Karnofsky performance status (KPS), temporalis muscle thickness), molecular factors (MGMT promoter methylation, EGFR amplification, TERT promoter mutation, and TP53 mutation status), treatment factors (extent of resection, and RT dose), and pretreatment laboratory parameters (serum De Ritis ratio, glucose level, neutrophil-to-lymphocyte ratio, platelet count, and systemic immune-inflammation index) were included in the analysis. The primary endpoint was overall survival (OS). Results: In total, 490 patients were included in the analysis. The median follow-up period was 12.3 months (range, 1.6-149.9 months). Median OS was significantly prolonged in patients with De Ritis ratioâ <â 1.2 (18.2 vs 15.3 months, Pâ =â .022) and in patients with glucose levelâ <â 150 mg/dL (18.7 vs 16.5 months, Pâ =â .034) per univariate analysis. In multivariate analysis, KPSâ ≥â 70, MGMT promoter methylation, extent of resection greater than partial resection, De Ritis ratioâ <â 1.2, and glucose levelâ <â 150 mg/dL were significant prognostic factors for improved OS. Conclusions: Along with well-known prognostic factors, pre-RT serum biomarkers, including the De Ritis ratio and glucose level, also had prognostic value in elderly patients with glioblastoma treated with TMZ-based chemoradiation.
RESUMO
The study objective was to evaluate the potential production of polyhydroxyalkanoates (PHAs), a biodegradable plastic material, by Paracoccus haeundaensis for which PHA production has never been reported. To identify the most effective nitrogen-limited culture conditions for PHAs production from this bacterium, batch fermentation using glucose concentrations ranging from 4 g l-1 to 20 g l-1 with a fixed ammonium concentration of 0.5 g l-1 was carried out at 30°C and pH 8.0. A glucose supplement of 12 g l-1 produced the highest PHA concentration (1.6 g l-1) and PHA content (0.63 g g-1) thereby identifying the optimal condition for PHA production from this bacterium. Gas chromatography-mass spectrometry analysis suggests that P. haeundaensis mostly produced copolymer types of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [P(3HB-co-3HV)] from glucose concentrations at 12 g l-1 or higher under the nitrogen-limited conditions. When several other single carbon sources were evaluated for the most efficient PHA production, fructose provided the highest biomass (2.8 g l-1), and PHAs (1.29 g l-1) concentrations. Results indicated that this bacterium mostly produced the copolymers P(3HB-co-3HV) from single carbon sources composing a range of 93-98% of 3-hydroxybutyrate and 2-7% of 3-hydroxyvalerate, whereas mannose-supplemented conditions produced the only homopolymer type of P(3HB). However, when propionic acid as a secondary carbon source were supplemented into the media, P. haeundaensis produced the copolymer P(3HB-co-3HV), composed of a 50% maximum monomeric unit of 3-hydroxyvaleric acid (3HV). However, as the concentration of propionic acid increased, cell biomass and PHAs concentrations substantially decreased due to cell toxicity.
Assuntos
Paracoccus , Ácidos Pentanoicos , Poliésteres , Poli-Hidroxialcanoatos , Poli-Hidroxibutiratos , Propionatos , Poliésteres/química , Carbono , Hidroxibutiratos , Glucose , NitrogênioRESUMO
BACKGROUND: The inferior temporal septum (ITS) is a fibrous adhesion between the superficial temporal fascia and the superficial layer of the deep temporal fascia. This study identified detailed the anatomical relationship between the ITS and the temporal branch of the facial nerve (TBFN) for facial nerve preservation during temple interventions. METHODS: Among 33 Korean cadavers, 43 sides of TBFNs in temporal regions were dissected after identifying the ITS between the superficial temporal fascia and superficial layer of the deep temporal fascia through blunt dissection. The topography of the ITS and TBFN were investigated with reference to several facial landmarks. Regional relationships with the ITS and TBFN within the temporal fascial layers were histologically defined from five specimens. RESULTS: At the level of the inferior orbital margin by the tragion, the mean distances from the lateral canthus to the anterior and posterior branches of the TBFN were 5 and 6.2 cm, respectively. At the lateral canthus level, the mean distance from the lateral canthus to the posterior branch of the TBFN was similar to that to the ITS, at 5.5 cm. At the superior orbital margin level, the posterior branch of the TBFN ran cranial to the ITS adjacent to the frontotemporal region. The TBFN ran through the subsuperficial temporal fascia layer and the nerve fibers located cranially, and within the ITS meshwork in the upper temporal compartment. CONCLUSION: The area of caution during superficial temporal fascia interventions related to the TBFN was clearly identified in the upper temporal compartment, which is known to lack important structures.
Assuntos
Nervo Facial , Zigoma , Humanos , Nervo Facial/anatomia & histologia , Tela Subcutânea , Fáscia/inervação , Face , CadáverRESUMO
Zinc oxide (ZnO) nanoparticles (NPs) are utilized as a zinc (Zn) fortifier in processed foods where diverse food additives can be present. Among them, additive solvents may strongly interact with ZnO NPs by changing the dispersion stability in food matrices, which may affect physico-chemical and dissolution properties as well as the cytotoxicity of ZnO NPs. In this study, ZnO NP interactions with representative additive solvents (methanol, glycerin, and propylene glycol) were investigated by measuring the hydrodynamic diameters, solubility, and crystallinity of ZnO NPs. The effects of these interactions on cytotoxicity, cellular uptake, and intestinal transport were also evaluated in human intestinal cells and using in vitro human intestinal transport models. The results revealed that the hydrodynamic diameters of ZnO NPs in glycerin or propylene glycol, but not in methanol, were significantly reduced, which is probably related to their high dispersion and increased solubility under these conditions. These interactions also caused high cell proliferation inhibition, membrane damage, reactive oxygen (ROS) generation, cellular uptake, and intestinal transport. However, the crystal structure of ZnO NPs was not affected by the presence of additive solvents. These findings suggest that the interactions between ZnO NPs and additive solvents could increase the dispersion and solubility of ZnO NPs, consequently leading to small hydrodynamic diameters and different biological responses.
RESUMO
Cholesterol sulfate (CS) is an activator of retinoic acid-related orphan receptor α (RORα). CS treatment or RORα overexpression attenuates osteoclastogenesis in a collagen-induced arthritis mouse model. However, the mechanism by which CS and RORα regulate osteoclast differentiation remains largely unknown. Thus, we aimed to investigate the role of CS and RORα in osteoclastogenesis and their underlying mechanism. CS inhibited osteoclast differentiation, but RORα deficiency did not affect osteoclast differentiation and CS-mediated inhibition of osteoclastogenesis. CS enhanced adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and sirtuin1 (Sirt1) activity, leading to nuclear factor-κB (NF-κB) inhibition by decreasing acetylation at Lys310 of p65. The NF-κB inhibition was restored by AMPK inhibitor, but the effects of CS on AMPK and NF-κB were not altered by RORα deficiency. CS also induced osteoclast apoptosis, which may be due to sustained AMPK activation and consequent NF-κB inhibition, and the effects of CS were significantly reversed by interleukin-1ß treatment. Collectively, these results indicate that CS inhibits osteoclast differentiation and survival by suppressing NF-κB via the AMPK-Sirt1 axis in a RORα-independent manner. Furthermore, CS protects against bone destruction in lipopolysaccharide- and ovariectomy-mediated bone loss mouse models, suggesting that CS is a useful therapeutic candidate for treating inflammation-induced bone diseases and postmenopausal osteoporosis.
Assuntos
Reabsorção Óssea , Ésteres do Colesterol , NF-kappa B , Animais , Feminino , Camundongos , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Diferenciação Celular , NF-kappa B/metabolismo , Osteoclastos/metabolismo , Osteogênese , Ligante RANK/farmacologia , Sirtuína 1/genética , Sirtuína 1/metabolismo , Ésteres do Colesterol/farmacologia , Ésteres do Colesterol/uso terapêuticoRESUMO
Background and purpose: Consolidatory radiotherapy in form of stereotactic body radiation therapy (SBRT) with an ablative dose following induction chemotherapy is emerging as a promising treatment scheme for unresectable pancreatic cancer. Outcomes of given treatment at a single center for contiguous patients with unresectable pancreatic cancer were evaluated to build the optimal treatment strategy. Materials and methods: In this retrospective study, a total of 50 patients with unresectable pancreatic cancer who underwent induction chemotherapy and ablative dose SBRT were included. SBRT dose was 40-50 Gy in five fractions. Two strategies were adopted to adhere to the organs at risk (OAR) dose constraints: simultaneous integrated protection (SIP) technique and magnetic resonance (MR)-guided adaptive technique. Overall survival (OS) and local progression-free survival (LPFS) were calculated from the start date of SBRT. Results: The median follow-up period for survivors was 21.1 months (range, 6.2-61.0 months). Eleven (22.0%) patients underwent resection after SBRT, which were all R0 resection. In patients with non-metastatic disease, the median OS was 26.5 months (range, 4.1-61.0 months), and the 1- and 3-year LPFS were 90.0% (95% confidence interval [CI], 72.0-96.7%) and 57.4% (95% CI, 31.7-76.4%), respectively. Patients with oligometastatic disease had inferior survival outcomes, but there was no survival difference among responders to induction chemotherapy. In the multivariable analysis, tumor size ≤4 cm, non-metastatic status, and good response to induction chemotherapy were associated with improved LPFS. In dosimetric analysis, GTV Dmin ≥50.5 Gy was the strongest prognosticator against local progression. Grade ≥3 adverse events occurred in two (4.0%) patients with non-adaptive RT, but none in patients with MR-guided adaptive RT. Conclusion: Ablative dose SBRT following induction chemotherapy is an effective strategy for selected patients with unresectable pancreatic cancer. The SIP technique and MR-guided adaptive RT were attributed to minimizing the risk of adverse events. Further studies are needed to identify the best candidates for consolidatory SBRT in unresectable pancreatic cancer.
RESUMO
BACKGROUND AND PURPOSE: We evaluated volumetric changes in the gray matter (GM) after radiotherapy (RT) and identified factors that were strongly associated with GM volume reduction. MATERIALS AND METHODS: A total of 461 magnetic resonance imagings (MRI) from 105 glioma patients treated with postoperative RT was retrospectively analyzed. Study patients' MRIs were collected at five time points: before RT and 1 month, 6 months, 1 year, and 2 years after RT. Using the 'FastSurfer' platform, a deep learning-based neuroimaging pipeline, 73 regions were automatically segmented from longitudinal MRIs and their volumetric changes were calculated. Regions were grouped into 10 functional fields. A multivariable linear mixed-effects model was established to identify the potential predictors of significant volume reduction. RESULTS: The median age was 50 years (range, 16-86 years). Forty-seven (44.8 %) patients were female and 68 (64.8 %) had glioblastoma. Postoperative RT was delivered at 54-60 Gy with or without concurrent chemotherapy. At 2 years after RT, the median volumetric changes in the overall, ipsilateral, and contralateral GM were -3.5%, -4.5%, and -2.4%, respectively. The functional fields of cognition and execution of movement showed the greatest volume reductions. In the multivariable linear mixed model, female sex (normalized coefficient = -0.14, P < 0.001) and the interaction between age at RT and days after RT (normalized coefficient = -6.48e-6, P < 0.001) were significantly associated with GM reduction. The older patients received RT, the greater volume reduction was seen over time. However, in patients with relatively younger age (e.g., 45, 50, and 60 years for hippocampus, Broca area, and Wernicke area, respectively), the volume was not significantly reduced. CONCLUSIONS: GM volume reduction was identified after RT that could lead to long-term treatment sequelae. Particularly for susceptible patients, individualized treatment and prevention strategies are needed.
Assuntos
Glioma , Substância Cinzenta , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Glioma/diagnóstico por imagem , Glioma/radioterapia , Glioma/patologia , Neuroimagem , Encéfalo/patologiaRESUMO
Importance: In clinical practice, assessment schedules are often arbitrarily determined after definitive treatment of head and neck cancer (HNC), producing heterogeneous and inconsistent surveillance plans. Objective: To establish an optimal assessment schedule for patients with definitively treated locally advanced HNC, stratified by the primary subsite and HPV status, using a parametric model of standardized event-free survival curves. Design, Setting, and Participants: This was a retrospective study including 2 tertiary referral hospitals and a total of 673 patients with definitive locoregional treatment of locally advanced HNC (227 patients with nasopharyngeal cancer [NPC]; 237 patients with human papillomavirus-positive oropharyngeal cancer [HPV+ OPC]; 47 patients with HPV-negative [HPV-] OPC; 65 patients with hypopharyngeal cancer [HPC]; and 97 patients with laryngeal cancer [LC]). Patients had received primary treatment in 2008 through 2019. The median (range) follow-up duration was 57.8 (6.4-158.1) months. Data analyses were performed from April to October 2021. Main Outcomes and Measures: Tumor recurrence and secondary malignant neoplasms. Event-free survival was defined as the period from the end of treatment to occurrence of any event. Event-free survival curves were estimated using a piecewise exponential model and divided into 3 phases of regular follow-up. A 5% event rate criterion determined optimal follow-up time point and interval. Results: The median (range) age of the 673 patients at HNC diagnosis was 58 (15-83) years; 555 (82.5%) were men; race and ethnicity were not considered. The event rates of NPC, HPV+ OPC, HPV- OPC, HPC, and LC were 18.9% (43 of 227), 14.8% (35 of 237), 36.2% (17 of 47), 44.6% (29 of 65), and 30.9% (30 of 97), respectively. Parametric modeling demonstrated optimal follow-up intervals for HPC, LC, and NPC, respectively, every 2.1, 3.2, and 6.1 months; 3.7, 5.6, and 10.8 months; and 9.1, 13.8, and 26.5 months until 16.5, 16.5 to 25.0, and 25.0 to 99.0 months posttreatment (open follow-up thereafter). For HPV- OPC, assessment was recommended every 2.7, 4.8, and 11.8 months until 16.5, 16.5 to 25.0, and 25 to 99 months posttreatment, respectively. In contrast, HPV+ OPC optimal intervals were every 7.7, 13.7, and 33.7 months until 16.5, 16.5 to 25.0, and 25 to 99 months posttreatment, respectively. Five, 4, 12, 15, and 10 follow-up visits were recommended for NPC, HPV+ OPC, HPV- OPC, HPC, and LC, respectively. Conclusions and Relevance: This retrospective cohort study using parametric modeling suggests that the HNC assessment schedules should be patient tailored and evidence based to consider primary subsites and HPV status. Given limited health care resources and rising detection rates and costs of HNC, the guidelines offered by these findings could benefit patients and health systems and aid in developing future consensus guidelines.
Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Hipofaríngeas , Neoplasias Laríngeas , Neoplasias Nasofaríngeas , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Estudos Retrospectivos , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/terapia , Infecções por Papillomavirus/diagnóstico , Neoplasias Nasofaríngeas/complicações , Intervalo Livre de Progressão , Recidiva Local de Neoplasia/terapia , Recidiva Local de Neoplasia/complicações , Neoplasias Orofaríngeas/terapia , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias Hipofaríngeas/complicações , Neoplasias Laríngeas/terapia , Neoplasias Laríngeas/complicações , SobreviventesRESUMO
BACKGROUND: The elevator muscles of the upper lip are the levator labii superioris alaeque nasi, levator labii superioris, and zygomaticus minor muscles, which function by means of their insertions into the skin of the upper lip. However, many textbooks and journal articles state that no muscle fibers are present on the orbicularis oris muscle in the upper lip. The authors attempted to determine whether there is a superficial muscle layer in addition to the orbicularis oris muscle in the upper lip. METHODS: The authors performed gross dissections of 10 formalin-fixed cadavers and applied micro-computed tomography to six formalin-fixed cadavers. The fine dissection of the upper lip was performed in a layer-by-layer manner that elucidated its muscle layers. The entire layer of the upper lip was separated and pretreated with phosphotungstic acid for micro-computed tomography. The samples used for micro-computed tomography were repurposed for use in histologic analysis. An ultrasonography study was also performed. RESULTS: The presence of a muscle layer on the orbicularis oris muscle was confirmed in all samples. The elevator muscle fibers of the upper lip formed a layer by combining with connective tissue. Micro-computed tomography indicated lower terminal insertions of the elevator muscles throughout the upper lip. All parts of the upper lip skin were inserted into the orbicularis oris muscle. The histologic findings were similar to those of micro-computed tomography. CONCLUSION: The authors' findings could be used to improve aesthetic and surgical procedures performed on the upper lip, such as correction of gummy smile and transverse upper labial crease, or postresection reconstruction of the upper lip.
Assuntos
Estética Dentária , Lábio , Humanos , Lábio/cirurgia , Microtomografia por Raio-X , Sorriso , Gengiva , Músculos Faciais/cirurgia , Cadáver , FormaldeídoRESUMO
Using a mutant of Mycobacterium smegmatis lacking the major aa3 cytochrome c oxidase of the electron transport chain (Δaa3), we demonstrated that inhibition of the respiratory electron transport chain led to an increase in antibiotic resistance of M. smegmatis to isoniazid, rifampicin, ethambutol, and tetracycline. The alternative sigma factors SigB and SigE were shown to be involved in an increase in rifampicin resistance of M. smegmatis induced under respiration-inhibitory conditions. As in Mycobacterium tuberculosis, SigE and SigB form a hierarchical regulatory pathway in M. smegmatis through SigE-dependent transcription of sigB. Expression of sigB and sigE was demonstrated to increase in the Δaa3 mutant, leading to upregulation of the SigB-dependent genes in the mutant. The pho U2 (MSMEG_1605) gene implicated in a phosphate-signaling pathway and the MSMEG_1097 gene encoding a putative glycosyltransferase were identified to be involved in the SigB-dependent enhancement of rifampicin resistance observed for the Δaa3 mutant of M. smegmatis. The significance of this study is that the direct link between the functionality of the respiratory electron transport chain and antibiotic resistance in mycobacteria was demonstrated for the first time using an electron transport chain mutant rather than inhibitors of electron transport chain.
Assuntos
Mycobacterium smegmatis , Mycobacterium tuberculosis , Proteínas de Bactérias/metabolismo , Transporte de Elétrons , Regulação Bacteriana da Expressão Gênica , Mycobacterium smegmatis/genética , Mycobacterium tuberculosis/genética , Rifampina/metabolismo , Rifampina/farmacologia , Transdução de SinaisRESUMO
In the current scenario of anthropogenic climate change, carbon credit security is becoming increasingly important worldwide. Topsoil is the terrestrial ecosystem component with the largest carbon sequestration capacity. Since soil organic matter (SOM), which is mostly composed of organic carbon, and can be affected by rainfall, cultivation, and pollutant inflow, predicting SOM content through regular monitoring is necessary to secure a stable carbon sink. In addition, topsoil in the Republic of Korea is vulnerable to erosion due to climate, topography, and natural and anthropogenic causes, which is also a serious issue worldwide. To mitigate topsoil erosion, establish an efficient topsoil management system, and maximize topsoil utilization, it is necessary to construct a database or gather data for the construction of a database of topsoil environmental factors and topsoil composition. Spectroscopic techniques have been used in recent studies to rapidly measure topsoil composition. In this study, we investigated the spectral characteristics of the topsoil from four major rivers in the Republic of Korea and developed a machine learning-based SOM content prediction model using spectroscopic techniques. A total of 138 topsoil samples were collected from the waterfront area and drinking water protection zone of each river. The reflection spectrum was measured under the condition of an exposure time of 136 ms using a spectroradiometer (Fieldspec4, ASD Inc., Alpharetta, GA, USA). The reflection spectrum was measured three times in wavelengths ranging from 350 to 2500 nm. To predict the SOM content, partial least squares regression and support vector regression were used. The performance of each model was evaluated through the coefficient of determination (R2) and root mean square error. The result of the SOM content prediction model for the total topsoil was R2 = 0.706. Our findings identified the important wavelength of SOM in topsoil using spectroscopic technology and confirmed the predictability of the SOM content. These results could be used for the construction of a national topsoil database.
Assuntos
Ecossistema , Solo , Carbono , Mudança Climática , Solo/química , Aprendizado de Máquina SupervisionadoRESUMO
The facial artery is the main artery supplying blood to the face and is known to have facial branches of the inferior labial, superior labial, lateral nasal and angular arteries. These known major branches of facial artery run medially, however, there are sometimes branches of the facial artery heading laterally. The purpose of the present study was to investigate the lateral branches of the facial artery in face. We dissected facial branches of the facial artery in 74 cadaveric hemifaces. We investigated the presence of the lateral branches of the facial artery. Following parameters were investigated: lateral branch presence, the location of its origin, and the lateral branch diameter. Among the lateral branches, we evaluated the prevalence and diameter of the premasseteric branch. Lateral branches were observed in 48 of the 74 hemifaces (64.9%). The total number was 81 in the 48 hemifaces. The most common origin was between the inferior border of the mandible and inferior labial artery origin (42 of 81, 51.9%). The mean diameter of all lateral branches of the facial artery was 0.7 mm. Among the lateral branches, the premasseteric branches were present in 38 of 74 specimen (51.4%) and the mean diameter was 0.8 mm. The lateral branches of the facial artery may be registered in Terminologia Anatomica based on their prevalence. Accurate knowledge of the anatomy of the lateral branches of the facial artery is helpful for clinicians to avoid complications during facial procedures or maxillofacial surgeries.
Assuntos
Face , Nariz , Vasos Coronários , Face/irrigação sanguínea , Humanos , Mandíbula , Nariz/irrigação sanguíneaRESUMO
Nonalcoholic steatohepatitis (NASH) is a liver disease characterized by fat accumulation and chronic inflammation in the liver. Dynein light chain of 8 kDa (LC8) was identified previously as an inhibitor of nuclear factor kappa B (NF-κB), a key regulator of inflammation, however, its role in NASH remains unknown. In this study, we investigated whether LC8 can alleviate NASH using a mouse model of methionine and choline-deficient (MCD) diet-induced NASH and examined the underlying mechanism. LC8 transgenic (Tg) mice showed lower hepatic steatosis and less progression of NASH, including hepatic inflammation and fibrosis, compared to wild-type (WT) mice after consuming an MCD diet. The hepatic expression of lipogenic genes was lower, while that of lipolytic genes was greater in LC8 Tg mice than WT mice, which might be associated with resistance of LC8 Tg mice to hepatic steatosis. Consumption of an MCD diet caused oxidative stress, IκBα phosphorylation, and subsequent p65 liberation from IκBα and nuclear translocation, resulting in induction of proinflammatory cytokines and chemokines. However, these effects of MCD diet were reduced by LC8 overexpression. Collectively, these results suggest that LC8 alleviates MCD diet-induced NASH by inhibiting NF-κB through binding to IκBα to interfere with IκBα phosphorylation and by reducing oxidative stress via scavenging reactive oxygen species. Thus, boosting intracellular LC8 could be a potential therapeutic strategy for patients with NASH.
Assuntos
Dineínas , NF-kappa B , Hepatopatia Gordurosa não Alcoólica , Estresse Oxidativo , Animais , Colina/metabolismo , Dineínas do Citoplasma , Dieta , Modelos Animais de Doenças , Dineínas/genética , Dineínas/metabolismo , Inflamação/metabolismo , Fígado/metabolismo , Fígado/patologia , Metionina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/metabolismo , Hepatopatia Gordurosa não Alcoólica/genéticaRESUMO
The current study investigated the anti-neuroinflammatory effects and mechanisms of astragalin (Ast) and isoquercitrin (Que) isolated from chamchwi (Aster scaber Thunb.) in the lipopolysaccharide (LPS)-activated microglia and hippocampus of LPS induced mice. LPS induced increased cytotoxicity, nitric oxide (NO) production, antioxidant activity, reactive oxygen species (ROS), inducible nitric oxide synthase (iNOS) expression, the release of pro-inflammatory cytokines, protein kinase B phosphorylation, and mitogen-activated protein kinases (MAPK) phosphorylation in LPS-treated microglial cells. Intraperitoneal injection of LPS also induced neuroinflammatory effects in the murine hippocampus. Ast and Que significantly reduced LPS-induced production of NO, iNOS, and pro-inflammatory cytokines in the microglia and hippocampus of mice. Therefore, anti-inflammatory effects on MAPK signaling pathways mediate microglial cell and hippocampus inflammation. In LPS-activated microglia and hippocampus of LPS-induced mice, Ast or Que inhibited MAPK kinase phosphorylation by extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 signaling proteins. Ast and Que inhibited LPS-induced ROS generation in microglia and increased 1,1-diphenyl-2-picrylhydrazyl radical scavenging. In addition, LPS treatment increased the heme oxygenase-1 level, which was further elevated after Ast or Que treatments. Ast and Que exert anti-neuroinflammatory activity by down-regulation of MAPKs signaling pathways in LPS-activated microglia and hippocampus of mice.
RESUMO
BACKGROUND: To evaluate the efficacy and safety of reducing target volume in definitive radiotherapy for HPV-associated tonsil cancer. METHODS: A single-institution cohort of 90 patients with human papillomavirus (HPV)-associated tonsil cancer who received definitive radiotherapy with a 5-mm expansion from the gross tumor volume to clinical target volume between 2008 and 2019 were included. The overlapping volume of initial planning target volume and the recurrent tumor was calculated and categorized as one of three failure types: in-field: ≥95%; marginal-field: 50%-94%; and out-field: <50%. RESULTS: With a median follow-up of 59.4 months, the 3-year and 5-year local control rates were 94.4% and 92.8%, respectively. A total of seven local failures were identified, of which 4 (4.4%) were in-field, 2 (2.2%) were marginal-field, and 1 (1.1%) was out-field. Grade 3 acute and late toxicities developed in 30 (33.3%) and 5 (5.6%) patients, respectively. CONCLUSIONS: Reducing target volume could be an alternative option for selected patients with HPV-associated tonsil cancer.
Assuntos
Alphapapillomavirus , Neoplasias Tonsilares , Humanos , Recidiva Local de Neoplasia/radioterapia , Papillomaviridae , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Neoplasias Tonsilares/radioterapiaRESUMO
ABSTRACT: The zygomatico-orbital artery (ZOA) originating from the superficial temporal artery and supplying the lower temporal region superficially has been reported. Previous studies of this artery have used definitions that are too ambiguous for the results to be directly adapted to clinical practice, including since they have resulted in marked variations in the reported incidence ofthe artery. This study dissected 193 hemifaces of 123 fixed human cadavers aged 36 to 102âyears (119 males and 74 females). The authors investigated the ZOA based on the following definition: (1) it originates from the superficial temporal artery, (2) it runs mostly above the zygomatic arch, and (3) it terminates below the superior border of the orbicularis oculi muscle. The incidence of the ZOA was 22.8% (44 cases of 193 sides), and its mean diameter was 1.1âmm. The meanvertical distances from the superior borderofthe zygomatic arch to the artery were 29.6, 17.8, and 2.9âmm at the jugale, zygion, and the origin of the ZOA, respectively. An accurate definition of the ZOA and accurate knowledge of its incidence and course could be important for clinicians to avoid unintentional complications in clinical practice.