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1.
PLoS One ; 19(6): e0303354, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38843274

RESUMO

BACKGROUND: Vietnam is experiencing an increasing prevalence of hypertension in its adult population. In addition to medical therapy, modifying adverse lifestyle practices is important for effective blood pressure control. There are limited data on unhealthy lifestyle practices in patients with chronic diseases, however, particularly among hypertensive patients living in rural Vietnam. Our study objectives were to examine the prevalence of unhealthy lifestyle practices and associated factors among rural Vietnamese adults with uncontrolled hypertension. METHODS: Data from the baseline survey of a cluster randomized trial among hypertensive Vietnamese adults (2017-2022) were utilized. Information on unhealthy lifestyle practices including smoking, excessive alcohol consumption, physical inactivity, and inadequate fruit and vegetable intake was collected from study participants. The primary study outcome was having ≥2 unhealthy lifestyle practices. A multivariable logistic regression model was used to examine factors associated with the primary study outcome. RESULTS: The mean age of the 671 patients was 67 years and 45.0% were men. Nearly three out of every four participants had one or fewer unhealthy practices, 24.0% had two, and 3.3% had three or all four unhealthy lifestyle practices. Men, individuals who did unpaid work or were unemployed, and individuals with hypertension level III were more likely to have ≥2 unhealthy lifestyle practices, whereas individuals with higher education were less likely to have ≥2 unhealthy lifestyle practices compared with respective comparison groups. CONCLUSIONS: We observed a high prevalence of unhealthy lifestyle practices among rural Vietnamese patients with uncontrolled hypertension. Several demographic factors were associated with a greater number of unhealthy lifestyle practices. Newer interventions and educational programs encouraging lifestyle modification practices are needed to control hypertension among adults living in rural settings of Vietnam.


Assuntos
Hipertensão , Estilo de Vida , Humanos , Hipertensão/epidemiologia , Masculino , Feminino , Vietnã/epidemiologia , Pessoa de Meia-Idade , Idoso , População Rural/estatística & dados numéricos , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , Prevalência , Fatores de Risco , Fumar/epidemiologia
2.
Cureus ; 16(4): e57961, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38738097

RESUMO

We present the case of a 13-year-old male with sickle cell disease (SCD) who presented to the emergency department with a severe headache secondary to calvarial infarcts with associated epidural and subgaleal hematomas. This case was complicated by external compression of the superior sagittal sinus by the hematomas as seen on magnetic resonance imaging. Management included supportive treatment of pain and swelling. This case emphasizes skull infarctions with associated hematomas as a possible differential diagnosis for patients with SCD presenting with headaches and scalp swellings.

3.
J Biol Chem ; : 107418, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38815867

RESUMO

ATP-citrate lyase (ACLY) links carbohydrate and lipid metabolism and provides nucleocytosolic acetyl-CoA necessary for protein acetylation. ACLY has two major splice isoforms: the full-length canonical "long" isoform and an uncharacterized "short" isoform in which exon 14 is spliced out. Exon 14 encodes 10 amino acids within a disordered region of the protein and includes at least 1 site that is dynamically phosphorylated. Both isoforms are expressed in healthy tissues to varying degrees. Analysis of human transcriptomic data revealed that the Percent Spliced In (PSI) of exon 14, i.e., the proportion of long isoform, is increased in several cancers and correlated with poorer overall survival in a pan-cancer analysis, though not in individual tumor types, which prompted us to explore potential biochemical and functional differences between ACLY isoforms. Here, we show that there are no discernible differences in enzymatic activity or stability between isoforms or phosphomutants of ACLY in vitro. Similarly, both isoforms and phosphomutants were able to rescue ACLY functions, including fatty acid synthesis and bulk histone acetylation, when re-expressed in Acly knockout cells. Deletion of Acly exon 14 in mice did not overtly impact development or metabolic physiology, nor did it attenuate tumor burden in a genetic model of intestinal cancer. Notably, expression of epithelial splicing regulatory protein 1 (ESRP1) is highly correlated with ACLY PSI. We report that ACLY splicing is regulated by ESRP1. In turn, both ESRP1 expression and ACLY PSI are correlated with specific immune signatures in tumors. Despite these intriguing patterns of ACLY splicing in healthy and cancer tissues, functional differences between the isoforms remain elusive.

4.
J Craniofac Surg ; 35(4): 1205-1208, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38738880

RESUMO

STUDY DESIGN: Cephalometric scans were compared before and after surgery to assess the degree of correction. Correlations between skeletal movements and survey outcomes were determined using multivariate regression analysis. OBJECTIVE: This study aims to identify relationships between subjective observer-reported improvements in esthetics and emotional appearance with specific surgical movements. METHODS: Ten patients at a single tertiary institution (average age: 18.1 ± 0.8), 9 males and 1 female, underwent orthognathic repair and had comprehensive cephalometric records. Standardized anterior posterior and lateral pre and postoperative photographs of patients were included in a survey to clinicians to assess noncognitive domains on a Likert Scale (1-10). CLEFT-Q was administered to gauge patient satisfaction in categories of appearance, speech, and quality of life. RESULTS: Per clinicians, multiple domains increased including facial attractiveness (4.1 ± 0.7 versus 7.3 ± 0.7, P < 0.001), friendliness (4.5 ± 0.4 versus 7.3 ± 0.5, P < 0.001), confidence (4.1 ± 0.4 versus 7.1 ± 0.4, P < 0.001), and recommendation for surgery decreased (8.9 ± 0.1 versus 3.6 ± 0.5, P < 0.001). Speech distress decreased with increased SNA and convexity, whereas Psychological and Social scores decreased with an increased ANB. Functional eating and drinking scores increased with maxillary depth. CONCLUSIONS: Orthognathic surgery improves many noncognitive domains in patients with cleft lip and palate as assessed by both patients and clinicians on all aspects of facial attractiveness and perception. These findings demonstrate objective bases of skeletal adjustments for perceived improvements in facial appearance and emotion.


Assuntos
Cefalometria , Fenda Labial , Fissura Palatina , Procedimentos Cirúrgicos Ortognáticos , Satisfação do Paciente , Humanos , Feminino , Masculino , Fenda Labial/cirurgia , Fenda Labial/psicologia , Fissura Palatina/cirurgia , Fissura Palatina/psicologia , Procedimentos Cirúrgicos Ortognáticos/psicologia , Adolescente , Qualidade de Vida , Adulto Jovem , Estética , Resultado do Tratamento , Inquéritos e Questionários
5.
J Craniofac Surg ; 35(4): 1092-1095, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38743287

RESUMO

OBJECTIVE: Postoperative nasal stents (NSs) are used to improve esthetic outcomes after primary or secondary cleft lip repair (CLR). Prior studies have utilized anthropometric measurements or physician assessment to determine the efficacy of NS, but data on caregiver-reported outcomes is limited. This study aims to assess caregiver compliance and satisfaction with postoperative NS. METHODS: The authors designed a survey to collect parent-reported postoperative NS usage outcomes. Parents of infants with cleft lip (CL) who used postoperative NS after primary CLR were approached through social media to complete the survey. Data were analyzed to determine factors impacting compliance, satisfaction, and parent-reported outcomes. RESULTS: Eighty-five parents completed the questionnaire, and 60% reported noncompliance with NS. Parents with male children (odds ratio: 5.08, P = 0.019) and patients with incomplete CL (odds ratio: 5.72, P = 0.006) were more likely to be non-compliant with NS for over a week. Complete CL and use of presurgical molding therapy were each associated with better overall experience with postoperative NS ( P = 0.002 and P = 0.037), higher appearance ratings ( P = 0.005 and P = 0.0008), and greater satisfaction with nostril shape after surgery ( P = 0.016 and P = 0.001). CONCLUSIONS: Despite limited literature related to caregiver-reported outcomes after postoperative NS for primary CLR, the authors' results align with what has been published regarding this topic. These results can help guide surgeons in counseling patients preoperatively. Larger, multi-institutional studies are needed to better delineate and address factors associated with compliance and satisfaction after NS therapy.


Assuntos
Fenda Labial , Cooperação do Paciente , Satisfação do Paciente , Stents , Humanos , Fenda Labial/cirurgia , Masculino , Feminino , Lactente , Inquéritos e Questionários , Pais/psicologia , Nariz/cirurgia , Nariz/anormalidades , Cuidados Pós-Operatórios , Resultado do Tratamento , Estética
6.
PLoS One ; 19(5): e0300446, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38820302

RESUMO

In cancer cells, the nuclear transport system is often disrupted, leading to abnormal localization of nuclear proteins and altered gene expression. This disruption can arise from various mechanisms such as mutations in genes that regulate nuclear transport, altered expression of transport proteins, and changes in nuclear envelope structure. Oncogenic protein build-up in the nucleus due to the disturbance in nuclear transport can also boost tumor growth and cell proliferation. In this study, we performed bioinformatic analyses of 23 key nuclear transport receptors using genomic and transcriptomic data from pancancer and head and neck squamous cell carcinoma (HNSCC) datasets from The Cancer Genome Atlas (TCGA) and Cancer Cell Line Encyclopedia and found that the total alteration frequency of 23 nuclear transport receptors in 2691 samples of the PCAWG Consortium was 42.1% and a high levels of genetic alterations was significantly associated with poor overall survival. Amplification was the most common type of genetic alterations, and results in the overexpression of nuclear transport receptors in HNSCC compared to normal tissues. Furthermore, our study revealed that seven out of eight cell cycle genes (CDK1, CDK2, CDK4, CDK6, CCNA1, CCNB1, and CCNE2) were significantly and positively correlated with nuclear transport receptor genes in TCGA pancancer and CCLE datasets. Additionally, functional enrichment analysis showed that nuclear transport receptor genes were mainly enriched in the adhesion junction, cell cycle, ERBB, MAPK, MTOR and WNT signaling pathways.


Assuntos
Neoplasias de Cabeça e Pescoço , Humanos , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Regulação Neoplásica da Expressão Gênica , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Transporte Ativo do Núcleo Celular , Linhagem Celular Tumoral
7.
Eur J Oncol Nurs ; 70: 102596, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38805952

RESUMO

OBJECTIVE: Limited knowledge on burden and quality of life (QoL) among cancer caregivers is available in low and middle income countries. This study aims to investigate the QoL, levels of burden, and their associations among Vietnamese cancer caregivers. METHODS: This study was conducted across three hospitals in Vietnam. 348 caregivers were recruited from January to June 2021. Data were collected by using socio-demographic questionnaires, the Zarit Burden Interview scale, and Caregiver Qol Cancer. The association between QoL and burden was analyzed by using multivariate linear regression. RESULTS: Older age (p = 0.03), employed (p = 0.01), and care more than 40 h (p = 0.007) were associated with a higher burden, respectively. QoL of financial concern had the lowest score (mean = 48.03, SD = 28.87), compared to the other subscale. Caregivers who had pre-existing health conditions, unstable work, spent more than 40 h per week, and took care dependent cancer patients were associated with a lower overall QoL score. Comparing to caregivers of no burden, those of mild burden had a lower QoL score by 10.70; while those of mild severe burden had the worse QoL (lower by 23.80 scores). CONCLUSIONS: Perceptional burden among caregivers is associated with QoL. Further policies are recommended to protect cancer caregivers, to alleviate the caregiving burden, and thus to improve the overall QoL.


Assuntos
Cuidadores , Neoplasias , Qualidade de Vida , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias/psicologia , Neoplasias/terapia , Vietnã , Cuidadores/psicologia , Cuidadores/estatística & dados numéricos , Adulto , Inquéritos e Questionários , Sobrecarga do Cuidador/psicologia , Idoso , Países em Desenvolvimento , Efeitos Psicossociais da Doença , Estudos Transversais
8.
PLoS One ; 19(3): e0300474, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38489305

RESUMO

BACKGROUND: In Vietnam, trastuzumab is included in social health insurance's benefits package with a reimbursement rate of 60%, but policymakers have been concerned about its cost-effectiveness. The research aims to evaluate the cost-effectiveness of one-year adjuvant trastuzumab therapy for early-stage breast cancer patients with human epidermal growth receptor 2 (HER2+) from a societal perspective. METHOD: A Markov model was developed and validated to estimate the lifetime cost and effectiveness (using life year and quality-adjusted life year) of one-year adjuvant trastuzumab therapy compared to chemotherapy (using paclitaxel) alone. Treatment efficacy and transition probabilities were estimated based on published trials (i.e., N9831, NSABP B-31, HERA, and BCIRG 006). Local cost and utility data were employed to capture the Vietnam context. One-way sensitivity analysis, probabilistic sensitivity analysis, threshold, and scenario analysis were also performed. RESULTS: One-year adjuvant trastuzumab therapy combined with chemotherapy compared to chemotherapy alone yielded an additional cost of 888,453,971VND (39,062 US$) with an additional 3.09 LYs and 1.61 QALYs, resulting in an ICER of 287,390,682 VND (12,635 US$) per LY gained, or 519,616,972 VND (22,845 US$) per QALY gained. The ICER exceeds the cost-effective threshold of 1- and 3-time GDP per capita by 6.3 and 2.1 times. The probabilistic sensitivity analysis shows similar results. According to one-way sensitivity analysis, ICERs were driven mainly by transition probabilities and trastuzumab price. One-year adjuvant trastuzumab therapy would be cost-effective at the 3-time GDP per capita threshold if the cost of Herceptin 150mg and 450mg vials were reduced by 56% and 54%, correspondingly. CONCLUSION: In Vietnam, one-year adjuvant trastuzumab therapy for early-stage breast cancer with HER2+ is not cost-effective. The research provided reliable and updated evidence to support policymakers in revising the health insurance benefit package. The policymakers should consider the options to reduce the cost of trastuzumab (e.g., regarding the use of trastuzumab biosimilars, price negotiation options, and options of optimizing the use of Herceptin vials among concurrent hospitalized breast cancer patients).


Assuntos
Medicamentos Biossimilares , Neoplasias da Mama , Humanos , Feminino , Trastuzumab/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Análise Custo-Benefício , Medicamentos Biossimilares/uso terapêutico , Vietnã , Receptor ErbB-2 , Anticorpos Monoclonais Humanizados/uso terapêutico , Quimioterapia Adjuvante , Anos de Vida Ajustados por Qualidade de Vida
9.
Cell Rep Med ; 5(3): 101469, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38508137

RESUMO

Fibrolamellar carcinoma (FLC) is a liver tumor with a high mortality burden and few treatment options. A promising therapeutic vulnerability in FLC is its driver mutation, a conserved DNAJB1-PRKACA gene fusion that could be an ideal target neoantigen for immunotherapy. In this study, we aim to define endogenous CD8 T cell responses to this fusion in FLC patients and evaluate fusion-specific T cell receptors (TCRs) for use in cellular immunotherapies. We observe that fusion-specific CD8 T cells are rare and that FLC patient TCR repertoires lack large clusters of related TCR sequences characteristic of potent antigen-specific responses, potentially explaining why endogenous immune responses are insufficient to clear FLC tumors. Nevertheless, we define two functional fusion-specific TCRs, one of which has strong anti-tumor activity in vivo. Together, our results provide insights into the fragmented nature of neoantigen-specific repertoires in humans and indicate routes for clinical development of successful immunotherapies for FLC.


Assuntos
Carcinoma Hepatocelular , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Receptores de Antígenos de Linfócitos T/genética , Linfócitos T/patologia , Terapia Baseada em Transplante de Células e Tecidos , Proteínas de Choque Térmico HSP40/genética , Subunidades Catalíticas da Proteína Quinase Dependente de AMP Cíclico/genética
10.
J Craniofac Surg ; 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38456609

RESUMO

INTRODUCTION: Radiographs (XRs), computed tomography (CT) scans, and cone-beam CT (CBCT) scans are utilized for assessment of secondary alveolar bone graft (SABG) in patients with cleft lip and palate (CLP). However, the optimal choice for imaging modality remains unclear. This study compares the image fidelity and safety profile for XR, CT, and CBCT in the assessment of patients with CLP who have undergone SABG. METHODS: Articles from MEDLINE and Elsevier Embase were screened. The primary outcome was graft success rate. Secondary outcomes were percent-by-volume of graft maintained and patient safety, defined by radiation exposure. A random effects model was used to calculate the pooled outcomes for each imaging modality. Chi-squared analysis was used to compare pooled outcomes between different imaging modalities. RESULTS: Of the 149 articles identified initially, 14 were included. Computed tomography exhibited a significantly higher image fidelity demonstrated by a lower graft success rate (62.0%) compared with both XR (72.6%, P<0.01) and CBCT (69.8%, P<0.01). Cone-beam CT had the lowest reported percent-by-volume of graft maintained (32.1%). Computed tomography had a higher mean radiation dosage (39.7 milligray) than what has been reported for both XR and CBCT. CONCLUSION: Computed tomography demonstrated lower graft success rates than both XR and CBCT, possibly indicating a higher image fidelity. However, compared with CBCT, CT may have a higher radiation exposure. Randomized trials and longitudinal studies are necessary to perform a direct comparison between CT and CBCT and to correlate the image fidelity of these modalities with clinical outcomes.

11.
Heliyon ; 10(4): e25920, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38384501

RESUMO

Background: Subdural hematoma following spinal anesthesia for cesarean delivery is a rare complication. Surgical removal of the hematoma is the standard treatment. However, there are still many patients who suffer permanent nerve damage of varying degrees after surgery. Cell therapy has recently shown great potential for treating nerve damage. Case presentation: This report described a case of paraplegia due to an epidural hematoma occurring after spinal anesthesia for cesarean section. The patient underwent surgery to remove the hematoma and rehabilitation afterward. However, no improvement was noted. Paralysis of the lower extremities associated with urinary retention and constipation persisted. The patient received three administrations of cell infusion: the first time with autologous bone marrow-derived mononuclear cells and the following two with autologous adipose mesenchymal/stromal cells. After three cell infusions, the patient was able to walk and could urinate and defecate voluntarily. Sensory and motor function were improved and MRI showed a decrease in adherence of the nerve roots and spinal cord. Conclusions: Our results demonstrated that cell therapy may ameliorate paralysis of the lower extremities as well as fecal and urinary function following spinal hematoma associated with spinal anesthesia.

12.
Res Sq ; 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38352564

RESUMO

Background Radiation-induced lung injury (RILI) via inflammation is a common adverse effect of thoracic radiation that negatively impacts patient quality of life and survival. Compound kushen injection (CKI), a botanical drug treatment, was examined for its ability to reduce RILI, and inflammatory responses and improve survival in mice exposed total lung irradiation (TLI). CKI's specific mechanisms of action were also evaluated. Methods C3H mice underwent TLI and were treated with CKI (2, 4, or 8 mL/kg) intraperitoneally once a day for 8 weeks. The effects of CKI on survival were estimated by Kaplan-Meier survival analysis and compared by log-rank test. RILI damage was evaluated by histopathology and micro-computed tomography (CT). Inflammatory cytokines and cyclooxygenase metabolites were examined by IHC staining, western blot, and ELISA. Results Pre-irradiation treatment with 4 or 8 mL/kg CKI starting 2 weeks before TLI or concurrent treatment with 8 mL/kg CKI were associated with a significantly longer survival compared with TLI vehicle-treated group ( P < 0.05). Micro-CT images evaluations showed that concurrent treatment with 8 mL/kg CKI was associated with significantly lower incidence of RILI ( P < 0.05). Histological evaluations revealed that concurrent TLI treatment of CKI (4 and 8 mL/kg) significantly reduced lung inflammation (p < 0.05). Mechanistic investigation showed that at 72 hours after radiation, TLI plus vehicle mice had significantly elevated serum IL6, IL17A, and TGF-ß levels compared with non-irradiated, age-matched normal mice; in contrast, levels of these cytokines in mice that received TLI plus CKI treatment were lower than those in the TLI plus vehicle-treated mice ( P < 0.05) and similar to the nonirradiated mice. IHC staining showed that the CKI treatment led to a reduction of TGF-ß positive cells in the lung tissues of TLI mice (P < 0.01). The concurrent CKI with TLI treatment group had a significant reduction in COX-2 activity and COX-2 metabolites compared with the TLI vehicle-treated group ( P < 0.05). Conclusions These data suggest that CKI treatment was associated with reduced radiation-induced inflammation in lung tissues, reduced RILI, and improved survival. Further investigation of CKI in human clinical trials as a potential radioprotector against RILI to improve patients' quality of life and survival is warranted.

13.
Bioimpacts ; 14(1): 27652, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38327632

RESUMO

Introduction: Patient-derived induced pluripotent stem cells (iPSCs) have been widely used as disease models to test new therapeutic strategies. Moreover, the regenerative potential of stem cells can be improved with the use of biologically active compounds. Our study was designed to explore the effect of honokiol, a small polyphenol molecule extracted from Magnolia officinalis, on the survival and culture time of iPSC-derived neurons from a sporadic Alzheimer's disease (AD) patient. This study aimed to generate iPSCs from peripheral blood mononuclear cells (PBMCs) of an AD patient using episomal plasmids with a nucleofector system and differentiate them into neurons. These iPSC-derived neurons were used to investigate the effect of honokiol extracted from M. officinalis on their survival and long-term cultures. Methods: IPSCs were generated from PBMCs of an AD patient by introducing Oct-3/4, Sox2, Klf4, L-Myc, and Lin28 using NucleofectorTM Technology. Differentiation of neurons derived from iPSCs was carried out using inducers and recognized by biomarkers. The viability of iPSC-derived neurons with the addition of honokiol extracted from the bark of M. officinalis was determined by the MTT analytical kit. Results: IPSCs were generated by reprogramming AD patient-derived PBMCs and subsequently converted into neurons. The survival and growth of iPSC-derived neurons were significantly enhanced by adding honokiol in the experiment conditions. Conclusion: AD iPSC-derived neurons had a high viability rate when cultured in the presence of honokiol. These results have shown that AD iPSC-derived neurons can be an excellent model for screening neurotrophic agents and improving the conditions for long-term cultures of human iPSC-derived neurons. Honokiol proves to be a potential candidate for cellular therapeutics against neurodegenerative disorders.

14.
Microb Genom ; 10(2)2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38407259

RESUMO

Enterobacteriaceae produce an arsenal of antimicrobial compounds including microcins, ribosomally produced antimicrobial peptides showing diverse structures and mechanisms of action. Microcins target close relatives of the producing strain to promote its survival. Their narrow spectrum of antibacterial activity makes them a promising alternative to conventional antibiotics, as it should decrease the probability of resistance dissemination and collateral damage to the host's microbiota. To assess the therapeutic potential of microcins, there is a need to understand the mechanisms of resistance to these molecules. In this study, we performed genomic analyses of the resistance to four microcins [microcin C, a nucleotide peptide; microcin J25, a lasso peptide; microcin B17, a linear azol(in)e-containing peptide; and microcin E492, a siderophore peptide] on a collection of 54 Enterobacteriaceae from three species: Escherichia coli, Salmonella enterica and Klebsiella pneumoniae. A gene-targeted analysis revealed that about half of the microcin-resistant strains presented mutations of genes involved in the microcin mechanism of action, especially those involved in their uptake (fhuA, fepA, cirA and ompF). A genome-wide association study did not reveal any significant correlations, yet relevant genetic elements were associated with microcin resistance. These were involved in stress responses, biofilm formation, transport systems and acquisition of immunity genes. Additionally, microcin-resistant strains exhibited several mutations within genes involved in specific metabolic pathways, especially for S. enterica and K. pneumoniae.


Assuntos
Bacteriocinas , Estudo de Associação Genômica Ampla , Bacteriocinas/genética , Antibacterianos/farmacologia , Imunidade Inata , Enterobacteriaceae/genética , Escherichia coli/genética , Klebsiella pneumoniae/genética , Peptídeos
15.
J Immunother Cancer ; 12(1)2024 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-38290769

RESUMO

BACKGROUND: Tumor-associated antigen (TAA)-specific CD8(+) T cells are essential for nivolumab therapy, and irradiation has been reported to have the potential to generate and activate TAA-specific CD8(+) T cells. However, mechanistic insights of T-cell response during combinatorial immunotherapy using radiotherapy and nivolumab are still largely unknown. METHODS: Twenty patients included in this study were registered in the CIRCUIT trial (ClinicalTrials.gov, NCT03453164). All patients had multiple distant metastases and were intolerance or had progressed after primary and secondary chemotherapy without any immune checkpoint inhibitor. In the CIRCUIT trial, eligible patients were treated with a total of 22.5 Gy/5 fractions/5 days of radiotherapy to the largest or symptomatic lesion prior to receiving nivolumab every 2 weeks. In these 20 patients, T-cell responses during the combinatorial immunotherapy were monitored longitudinally by high-dimensional flow cytometry-based, multiplexed major histocompatibility complex multimer analysis using a total of 46 TAAs and 10 virus epitopes, repertoire analysis of T-cell receptor ß-chain (TCRß), together with circulating tumor DNA analysis to evaluate tumor mutational burden (TMB). RESULTS: Although most TAA-specific CD8(+) T cells could be tracked longitudinally, several TAA-specific CD8(+) T cells were detected de novo after irradiation, but viral-specific CD8(+) T cells did not show obvious changes during treatment, indicating potential irradiation-driven antigen spreading. Irradiation was associated with phenotypical changes of TAA-specific CD8(+) T cells towards higher expression of killer cell lectin-like receptor subfamily G, member 1, human leukocyte antigen D-related antigen, T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain, CD160, and CD45RO together with lower expression of CD27 and CD127. Of importance, TAA-specific CD8(+) T cells in non-progressors frequently showed a phenotype of CD45RO(+)CD27(+)CD127(+) central memory T cells compared with those in progressors. TCRß clonality (inverted Pielou's evenness) increased and TCRß diversity (Pielou's evenness and Diversity Evenness score) decreased during treatment in progressors (p=0.029, p=0.029, p=0.012, respectively). TMB score was significantly lower in non-progressors after irradiation (p=0.023). CONCLUSION: Oligo-fractionated irradiation induces an immune-modulating effect with potential antigen spreading and the combination of radiotherapy and nivolumab may be effective in a subset of patients with gastric cancer.


Assuntos
Nivolumabe , Neoplasias Gástricas , Humanos , Nivolumabe/farmacologia , Nivolumabe/uso terapêutico , Linfócitos T CD8-Positivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Imunidade , Imunoterapia , Antígenos Comuns de Leucócito
16.
J Craniofac Surg ; 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38231188

RESUMO

OBJECTIVE: Though it has made significant strides, Vietnam remains a resource-constrained country of 98 million people. Vietnam National Children's Hospital (VNCH) provides tertiary care to a catchment of 40 million people and is the sole national children's hospital. As such, it is one of the few referral centers in the country equipped to take care of patients diagnosed with Pierre Robin sequence (PRS) as this requires pulmonary, critical care, otolaryngology, and plastic surgery expertise. Before 2015, the only surgical options were tongue lip adhesion or tracheostomy. Only 20% of patients successfully avoided tracheostomy, mechanical ventilation, or death. From 2015 to 2019, mandibular distraction osteogenesis (MDO) was introduced by visiting international surgeons on a short-term basis. Since 2020, local surgeons at VNCH have refined their technique and widely use MDO independently. This report seeks to capitulate their experience and identify factors leading to success. METHODS: A retrospective review was conducted of patients diagnosed with PRS at VNCH from 2015 to 2022. Paper records were digitized, translated, and reviewed for inclusion criteria, including demographics, indications, hospital course, and postoperative outcomes. RESULTS: Complete records satisfying inclusion criteria were available for 53 patients with a diagnosis of PRS who underwent MDO from 2020 to 2022. From 2015 to 2019, there were 19 cases of MDO, though records were incomplete. The median age at the time of MDO was 50 ± 43 days. Forty patients (75.5%) had isolated PRS and 13 (24.5%) were syndromic. Forty-four patients (83%) had a cleft palate. Fifty-one (96.2%) of patients required preoperative supplemental oxygen or mechanical ventilation. The active distraction and consolidation phase was 4.8 ± 1.3 months. The median days to discharge after surgery was 19.0 ± 8.3 days. Median weight at birth, at the time of surgery, and at the time of device removal were 6.8 ± 1.2, 7.7 ± 1.9, and 14.8 ± 2.8 pounds, respectively. Fifty-two patients (98.1%) had obstructive sleep apnea preoperatively with an average Apnea Hypopnea Index of 25.0 ± 10.6. Post-MDO, only 4 (7.5%) had obstructive sleep apnea and the average Apnea Hypopnea Index was 5.2 ± 0.6. No patients (0) required a tracheostomy for a 100% success rate. CONCLUSIONS: The tremendous success of the implementation of MDO by local surgeons in Vietnam after its introduction by visiting international surgeons illustrates a paradigm for capacity-enhancing global surgical endeavors. Mandibular distraction osteogenesis has replaced tongue lip adhesion as the surgical treatment of choice for PRS patients at VNCH. Surgical techniques can be transferred to operating environments with basic infrastructure through collaboration and resource optimization. These results demonstrate that global surgical engagement may be scalable and repeatable with direct benefits for patients in lower-middle-income countries.

17.
J Oleo Sci ; 73(1): 65-71, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38171732

RESUMO

Lyotropic liquid crystals (LLCs) are interesting wall-materials for encapsulation technology, in which monoacylglycerols (MAGs) are considered as potential ingredient for LLC formulation. This study, therefore, applied palm oil-based MAGs to encapsulate Gac fruit oils and compared the effect of two drying methods (freeze-drying and spray-drying) on the quality of products during storage. Wall-materials were prepared by ultrasound dispersing MAGs/water mixtures (40/60, w/w) into Pluronic solution (2%, w/w) to formulate LLC dispersions. Then, Gac fruit oils were encapsulated by freeze-drying and spray-drying. Various technologies were applied to characterize the properties of dispersions, the encapsulated powder morphology and the loading capacity. Obtained results showed that LLC dispersions made of palm oilbased MAG were micro- and nano-emulsions which were very convenient for encapsulating Gac fruit oils. For both drying methods, ß-carotene of Gac fruit oils was successfully entrapped by MAGs with a high loading capacity (200 µg ß-carotene/g powder). The degradation of encapsulated ß-carotene after four storage weeks was 10 - 40% and freeze-dried samples showed a better protection effect in comparison to spray-dried samples.


Assuntos
Frutas , beta Caroteno , Frutas/química , beta Caroteno/análise , Óleo de Palmeira/análise , Monoglicerídeos , Pós , Óleos/química , Liofilização
18.
Plast Reconstr Surg ; 153(1): 139e-145e, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37053453

RESUMO

SUMMARY: Velopharyngeal insufficiency (VPI) is a complication following primary palatoplasty that can lead to hypernasality of the voice and other speech problems. The conversion Furlow palatoplasty for VPI can be performed with the addition of buccal flaps to provide additional tissue for palatal repair. In this study, the authors aimed to determine the effectiveness of buccal flaps with conversion Furlow palatoplasty in secondary management of VPI. A retrospective review of patients undergoing surgical repair of VPI between 2016 and 2020 was performed. Patients underwent either conversion Furlow palatoplasty alone (FA) or conversion Furlow palatoplasty with buccal flaps (FB) for VPI after primary straight-line repair of the palate. The authors reviewed medical records to collect demographics, operative information, and preoperative and postoperative speech scores. Of the 77 patients in the study, 16 (21%) had a revision that incorporated buccal flaps. The median age at cleft palate revision surgery was 8.97 years in the FA group and 7.96 years in the FB group ( P = 0.337). In the FA group, four patients (7%) developed a postoperative fistula, compared with zero patients in the FB group. The average time to follow-up after revision surgery was 3.4 years (range, 7 months to 5.9 years). Both cohorts demonstrated a decrease in hypernasality and total parameter scores postoperatively. The use of buccal flaps in revision Furlow palatoplasty could decrease the risk for postoperative complications. The use of data from a larger patient population from multiple institutions is warranted to determine true significance. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.


Assuntos
Fissura Palatina , Doenças Nasais , Procedimentos de Cirurgia Plástica , Insuficiência Velofaríngea , Humanos , Fissura Palatina/cirurgia , Fissura Palatina/complicações , Insuficiência Velofaríngea/etiologia , Insuficiência Velofaríngea/cirurgia , Palato Mole/cirurgia , Procedimentos de Cirurgia Plástica/efeitos adversos , Retalhos Cirúrgicos/cirurgia , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Doenças Nasais/cirurgia , Resultado do Tratamento
19.
J Neurosurg Sci ; 68(2): 208-215, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37878249

RESUMO

INTRODUCTION: Baseline frailty status has been utilized to predict a wide range of outcomes and guide preoperative decision making in neurosurgery. This systematic review aims to analyze existing literature on the utilization of frailty as a predictor of neurosurgical outcomes. EVIDENCE ACQUISITION: We conducted a systematic review following PRISMA guidelines. Studies that utilized baseline frailty status to predict outcomes after a neurosurgical intervention were included in this systematic review. Studies that utilized sarcopenia as the sole measure of frailty were excluded. PubMed, EMBASE, and Cochrane library was searched from inception to March 1st, 2023, to identify relevant articles. EVIDENCE SYNTHESIS: Overall, 244 studies met the inclusion criteria. The 11-factor modified frailty index (mFI-11) was the most utilized frailty measure (N.=91, 37.2%) followed by the five-factor modified Frailty Index (mFI-5) (N.=80, 32.7%). Spine surgery was the most common subspecialty (N.=131, 53.7%), followed by intracranial tumor resection (N.=57, 23.3%), and post-operative complications were the most reported outcome (N.=130, 53.2%) in neurosurgical frailty studies. The USA and the Bowers author group published the greatest number of articles within the study period (N.=176, 72.1% and N.=37, 15.2%, respectively). CONCLUSIONS: Frailty literature has grown exponentially over the years and has been incorporated into neurosurgical decision making. Although a wide range of frailty indices exist, their utility may vary according to their ability to be incorporated in the outpatient clinical setting.


Assuntos
Fragilidade , Neurocirurgia , Humanos , Fragilidade/cirurgia , Fragilidade/complicações , Fatores de Risco , Procedimentos Neurocirúrgicos/efeitos adversos , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos
20.
Am J Clin Pathol ; 161(2): 162-169, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37788085

RESUMO

OBJECTIVES: Leukemia diagnosis in Vietnam is limited by a lack of hematopathology training and expert consultation as well as the cost of high-magnification digitization of hematology slides. Screen-sharing software allows international collaboration with experienced hematopathologists for improved diagnostic accuracy. METHODS: A hematopathology education and consultation program was proposed for Vietnam hospitals. By appointment, pathologists in Vietnam with access to a microscope camera, imaging software, and high-speed internet were invited to review slides and data with a volunteer board-certified hematopathologist in the United States using secure videoconferencing software. A single hospital in southern Vietnam assigned a pathologist proficient in English to access this service. All consultations from this site with clinicopathologic information were logged. After a 2-year period of online consultation, case slides for selected diagnoses were reviewed under the microscope in Vietnam to assess concordance. RESULTS: In total, 135 consultations were logged, 53 of which were for blood and bone marrow. T-cell large granular lymphocytic leukemia (T-LGLL) was 1 of the most frequent bone marrow consultation-related diagnoses; all diagnoses of this entity were confirmed by in-person microscopy (100% concordance). A records search and physician surveys found no prior documented diagnoses of T-LGLL made in Vietnam before this education and consultation program. CONCLUSIONS: Our virtual consultation model has improved patient care in Vietnam by providing correct diagnoses to inform best practices in treatment. As a result of our program, the first Vietnam diagnoses of T-LGLL were made and may help expand on the literature in this area. This model could provide cost-effective, real-time consultation and education services for pathologists in underserved communities.


Assuntos
Leucemia Linfocítica Granular Grande , Leucemia , Humanos , Microscopia , Leucemia Linfocítica Granular Grande/patologia , Vietnã , Encaminhamento e Consulta
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