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1.
Indian J Orthop ; 58(8): 1126-1133, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39087039

RESUMO

Purpose: Perception that extra-medullary fixation of these fractures are fraught with difficulties and deficiencies is becoming inappropriate. This device provides angular stable fixation retaining fracture biology with minimum interference to osseous and soft-tissue vascularity and it does not require reaming which destroys 80% of endosteal vasculature for 6-12 weeks. PFLCP averts iatrogenic fracture in lateral trochanteric wall (LTW) which is frequent with DHS, protects LTW from secondary fracture in post-operative period. Aim is to assess outcome of unstable proximal femur fracture fixation by PFLCP. Methods: Study included 64 from 2016 to 2020, divided in two groups. (A) Unstable intertrochanteric fracture and (B) subtrochanteric fracture (Seinsheimer types II-V). All fractures fixed by MIPO with PFLCP. Loss of reduction, infection, cut-out, cut-through, backing of screws, bending or breaking of plate and screw, malunion, non-union and revision were evaluated. Fracture healing and functional recovery assessed by Reborne Score and Parker Mobility Score (PMS) respectively. Results: Out of 64, 24 achieved pre-injury PMS, 32 declined by 1 point, 6 declined by 2 points and 1 by 3 points, one required revision. Using various parameters 37.5% patients had excellent results and 50% had good results, 9.38% had average and 3.12% had poor result. None reported non-union or breakage of plate. Conclusions: PFLCP provides angular stable fixation, torsional stability with high biomechanical strength to resist deforming stresses. MIPO avoids soft-tissue stripping reducing blood-loss, retains periosteal blood supply to inter-fragmentary bone fragments, enhancing fracture healing, reducing complications, such as delayed healing, nonunion, infection and implant failure.

2.
BMC Immunol ; 25(1): 42, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38977952

RESUMO

OBJECTIVE: Triple-Negative Breast Cancer (TNBC) is known for its aggressiveness and treatment challenges due to the absence of ER, PR, and HER2 receptors. Our work emphasizes the prognostic value of LCP1 (Lymphocyte cytosolic protein 1), which plays a crucial role in cell processes and immune cell activity, to predict outcomes and guide treatments in TNBC. METHODS: We explored LCP1 as a potential biomarker in TNBC and investigated the mRNA and protein expression levels of LCP1. We investigated different databases, including GTEX, TCGA, GEO, cBioPortal and Kaplan-Meier Plotter. Immunohistochemistry on TNBC and benign tumor samples was performed to examine LCP1's relationship with patient clinical characteristics and macrophage markers. We also assessed survival rates, immune cell infiltration, and drug sensitivity related to LCP1 using various bioinformatics tools. RESULTS: The results indicated that LCP1 expression was higher in TNBC tissues compared to adjacent normal tissues. However, high expression of LCP1 was significantly associated with favorable survival outcomes in patients with TNBC. Enrichment analysis revealed that genes co-expressed with LCP1 were significantly enriched in various immune processes. LCP1 showed a positive correlation with the infiltration of resting dendritic cells, M1 macrophages, and memory CD4 T cells, and a negative correlation with M2 macrophages. Further analysis suggested a link between high levels of LCP1 and increased survival outcomes in cancer patients receiving immunotherapy. CONCLUSION: LCP1 may serve as a potential diagnostic and prognostic biomarker for TNBC, which was closely associated with immune cell infiltration, particularly M1 and M2 macrophages. Our findings may provide valuable insights into immunotherapeutic strategies for TNBC patients.


Assuntos
Biomarcadores Tumorais , Linfócitos do Interstício Tumoral , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/imunologia , Neoplasias de Mama Triplo Negativas/mortalidade , Neoplasias de Mama Triplo Negativas/genética , Feminino , Biomarcadores Tumorais/metabolismo , Prognóstico , Linfócitos do Interstício Tumoral/imunologia , Regulação Neoplásica da Expressão Gênica , Macrófagos/imunologia , Macrófagos/metabolismo , Microambiente Tumoral/imunologia , Estimativa de Kaplan-Meier
3.
Cureus ; 16(6): e62534, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38887746

RESUMO

INTRODUCTION: Periprosthetic humeral fractures are a rare and increasing entity due to the rising number of shoulder arthroplasties. These fractures pose a significant challenge for surgeons, with incidence rates ranging from 1.2% to 19.4%. They can occur intraoperatively or as late complications, often influenced by trauma, prosthetic wear, or loosening. PATIENTS AND METHODS: A retrospective study was conducted on all patients admitted with periprosthetic humeral fractures over a four-year period (2018-2022). Inclusion criteria were postoperative periprosthetic humeral fractures with a minimum follow-up of six months. Exclusion criteria included intraoperative fractures, fractures of the glenoid or coracoid process, and cases with follow-up of less than six months or incomplete data. RESULTS: The study included six patients with an average age of 83.1 years, predominantly female (four females and two males). All fractures occurred postoperatively: four on reverse shoulder prostheses, one on an anatomical prosthesis, and one on a hemiarthroplasty. The mechanism was low-energy trauma, with fractures occurring an average of 96 months post-initial surgery. Fractures were classified using the Campbell system: three in region 4, two in region 3, and one in region 2. Radiographs showed four cemented and two uncemented stems. Three patients underwent surgical treatment with either prosthetic replacement using a long stem and fracture cerclage or locking compression plate (LCP). The remaining three patients were treated conservatively with a Sarmiento brace due to advanced age, bone fragility, low functional demand, and comorbidities. Radial nerve palsy was a complication in two patients post-trauma, with one recovering fully and the other not recovering before death due to associated complications. All fractures consolidated within an average of seven months (range: 5-8 months). Functional recovery was satisfactory with a median Constant-Murley Shoulder Score of 69 in surgically treated patients, with range of motion between 100 and 140 degrees. Only two conservatively treated patients achieved fracture consolidation, and functional recovery was inadequate. DISCUSSION: Managing periprosthetic humeral fractures remains challenging. Treatment goals include fracture healing, maintaining prosthetic stem stability, preserving glenohumeral motion, and restoring shoulder function. Despite various classification systems, the literature shows limited and variable data on incidence and treatment outcomes. Conservative treatment may be considered for stable implants and acceptable alignment, but surgical intervention is often necessary for displaced fractures or implant loosening. CONCLUSION: The management of periprosthetic humeral fractures requires a tailored, multidisciplinary approach to optimize outcomes and improve patient quality of life. With the increasing incidence of these fractures due to the growing use of shoulder arthroplasty, ongoing research and development of new techniques and therapeutic strategies are essential to address this clinical challenge effectively.

4.
J Orthop ; 55: 69-73, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38681826

RESUMO

Background: Since 2014, the VA-LCP Condylar Plate 4.5/5.0, Depuy Synthes, has been the preferred implant for these injuries at our institution, however, speculations have been made whether it is more prone to failure compared to other implants. Thus, the aim of the study was to describe the cohort treated with the VA-LCP Condylar Plate 4.5/5.0, Depuy Synthes, at our department from 2014 to 2020, including the number of failures. Secondary, whether specific outcome measures were significantly overrepresented in the failure group. Methods: Patients were identified through the hospital database, and demographic data was extracted from patient files. X-rays were evaluated for injury type, osteosynthesis characteristics, and whether the construct failed during follow-up. Thanks to the national patient record database a minimum of patients was lost to follow-up. Results: After exclusion 159 patients (165 osteosyntheses, descriptive part) and 108 patients (112 osteosyntheses, subgroup analysis) were eligible for inclusion. The VA-LCP Condylar Plate 4.5/5.0, Depuy Synthes, was used for most AO-type fractures and inserted as both neutralization, buttress, and bridging plates. Overall failure was seen in 8 % of osteosyntheses. Significantly more failures were seen in patients with increased Body Mass Index (BMI) (24 vs. 32, p = 0,046) and those treated for a periprosthetic fractures (41 % vs. 89 %, p = 0,005). We did not see an association between failure and plate length, bridge span, screw density or the degree of medial support. Conclusion: The VA-LCP Condylar Plate 4.5/5.0, Depuy Synthes is a versatile plate with failure rates comparable to previously reported studies. This study confirmed that elevated BMI may be a risk factor for failure, while other previously reported risk factors were not associated with failure in this study.

5.
Biomolecules ; 14(3)2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38540793

RESUMO

The plant hormone ethylene is a key regulator of plant growth, development, and stress adaptation. Many ethylene-related responses, such as abscission, seed germination, or ripening, are of great importance to global agriculture. Ethylene perception and response are mediated by a family of integral membrane receptors (ETRs), which form dimers and higher-order oligomers in their functional state as determined by the binding of Cu(I), a cofactor to their transmembrane helices in the ER-Golgi endomembrane system. The molecular structure and signaling mechanism of the membrane-integral sensor domain are still unknown. In this article, we report on the crystallization of transmembrane (TM) and membrane-adjacent domains of plant ethylene receptors by Lipidic Cubic Phase (LCP) technology using vapor diffusion in meso crystallization. The TM domain of ethylene receptors ETR1 and ETR2, which is expressed in E. coli in high quantities and purity, was successfully crystallized using the LCP approach with different lipids, lipid mixtures, and additives. From our extensive screening of 9216 conditions, crystals were obtained from identical crystallization conditions for ETR1 (aa 1-316) and ETR2 (aa 1-186), diffracting at a medium-high resolution of 2-4 Å. However, data quality was poor and not sufficient for data processing or further structure determination due to rotational blur and high mosaicity. Metal ion loading and inhibitory peptides were explored to improve crystallization. The addition of Zn(II) increased the number of well-formed crystals, while the addition of ripening inhibitory peptide NIP improved crystal morphology. However, despite these improvements, further optimization of crystallization conditions is needed to obtain well-diffracting, highly-ordered crystals for high-resolution structural determination. Overcoming these challenges will represent a major breakthrough in structurally determining plant ethylene receptors and promote an understanding of the molecular mechanisms of ethylene signaling.


Assuntos
Escherichia coli , Reguladores de Crescimento de Plantas , Cristalização , Escherichia coli/metabolismo , Etilenos/metabolismo
6.
Int J Biol Macromol ; 264(Pt 1): 130378, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38428774

RESUMO

Polyethylene is the most commonly used plastic product, and its biodegradation is a worldwide problem. Latex clearing protein derived from Streptomyces sp. strain K30 (LcpK30) has been reported to be able to break the carbon-carbon double bond inside oxidized polyethylene and is an effective biodegradation enzyme for polyethylene. However, the binding of the substrate to the enzyme was difficult due to the hydrophobic nature of polyethylene. Therefore, to further improve the efficiency of LcpK30, the effect of different anchor peptides on the binding capacity of LcpK30 to the substrate was screened in this study. The results of fluorescence confocal microscopy showed that the anchoring peptide LCI had the most significant improvement in effect and was finally selected for further application in a UV-irradiated PE degradation system. The degradation results showed that LCI was able to improve the degradation efficiency of LcpK30 by approximately 1.15 times in the presence of equimolar amounts of protein compared with wild-type. This study further improves the application of LcpK30 in the field of polyethylene degradation by modification.


Assuntos
Látex , Streptomyces , Látex/química , Polietileno , Proteínas de Bactérias/química , Peptídeos/metabolismo , Carbono/metabolismo , Biodegradação Ambiental
7.
Food Chem Toxicol ; 186: 114548, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38417537

RESUMO

The connection between continuous arsenic exposure and prostate cancer is already established. However, the exact mechanisms of arsenic tumorigenesis are far from clear. Here, we employed human prostate stromal immortalized cells (WPMY-1) continuous exposure to 1 and 2 µM arsenite for 29 weeks to identify the malignant phenotype and explore the underlying molecular mechanism. As expected, continuous low-dose arsenite exposure led to the malignant phenotype of WPMY-1 cells. Quantitative proteomics identified 517 differentially expressed proteins (DEPs), of which the most remarkably changed proteins (such as LCP1 and DDX58, etc.) and the bioinformatic analysis were focused on the regulation of cytoskeleton, cell adhesion, and migration. Further, cell experiments showed that continuous arsenite exposure altered cytoskeleton structure, enhanced cell adhesive capability, and raised the levels of reactive oxygen species (ROS), ATM, p-ATM, p-ERK1/2, and LCP1 proteins. N-acetylcysteine (NAC) treatment antagonized the increase of LCP1 proteins, and LCP1 knockdown partially restored F-actin organization caused by arsenic. Overall, the results demonstrated that ROS-ATM-ERK1/2 signaling pathway was involved in the activation of LCP1, leading to cytoskeleton alterations. These alterations are believed to play a significant role in arsenite-triggered tumor microenvironment cell-acquired malignant phenotype, which could provide potential biomarkers with therapeutic implications for prostate cancer.


Assuntos
Arsênio , Arsenitos , Neoplasias da Próstata , Masculino , Humanos , Linhagem Celular , Próstata , Espécies Reativas de Oxigênio , Arsenitos/toxicidade , Células Estromais , Fenótipo , Citoesqueleto , Microambiente Tumoral , Proteínas dos Microfilamentos , Proteínas HMGB
8.
Arch Microbiol ; 206(2): 71, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38252137

RESUMO

COVID-19 pandemic has generated high demand for natural rubber gloves (NR) leading to crucial issues of rubber waste and waste management such as burning, dumping, stockpiling, discarding waste in landfills. Hence, rubber biodegradation by microorganisms is an alternative solution to the problem. The biodegradation method is environmentally friendly but normally extremely slow. Numerous microorganisms can degrade NR as a source of carbon and energy. In this study, Rhodococcus pyridinivorans KU1 was isolated from the consortium CK from previous study. The 40% rubber weight loss was detected after incubated for 2 months. The bacterial colonization and cavities on the surface of rubber were identified using a scanning electron microscope (SEM). The result demonstrated the critical degradation of the rubber surface, indicating that bacteria can degrade rubber and use it as their sole carbon source. The result of whole-genome sequencing (WGS) revealed a gene that is 99.9% identical to lcp which is responsible for poly (cis-1,4-isoprene) degradation. The results from Meta16S rRNA sequencing showed that the microbial communities were slightly shifted during the 2-month degradation, depending on the presence of monomers or oligomers appeared during the degradation process. The majority of species were soil bacteria such as phylum Proteobacteria, Actinobacteria, and Firmicutes. Members of Pseudoxanthomonas seemed to be the dominant degraders throughout the degradation.


Assuntos
Rhodococcus , Borracha , Humanos , Pandemias , Firmicutes , Carbono
9.
Eur J Orthop Surg Traumatol ; 34(3): 1287-1296, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38071686

RESUMO

BACKGROUND: There has been no scientific mechanical assessment demonstrating the optimal fixation technique in multifragmentary fractures of the distal humeral shaft. The purpose of the present study was to compare the biomechanical performance of 5 fixation constructs as used in minimally invasive plating osteosynthesis (MIPO) for distal humeral shaft fractures. METHODS: Three-dimensional (3D) humerus model with 20 mm distal humeral shaft fracture gap simulating multifragmentary fracture was created from computed tomography data and virtually fixed by 5 fixation techniques as MIPO, i.e., anterior narrow dynamic compression plate (DCP), anterior narrow locking compression plate (LCP), anterior reversed proximal humeral internal locking system (R-PHILOS), extra-articular distal humerus locking compression plate (LCP-EADH), and anteromedial LCP. All constructs were biomechanically tested under 6 loading conditions by means of finite element analysis, i.e., 250-N axial compression, 7.5-N m internal rotation, 7.5-N m external rotation, 10-N m posterior bending, 10-N m valgus rotation, and 10-N m varus rotation. In addition, A 3D model of each construct was fabricated as 3D printed models. Fixations were applied to the 3D printing model which were later mechanically tested to validate the FE results. RESULTS: EQV stress exhibited on anterior narrow LCP and anterior R-PHILOS were comparable which were lower than other constructs under axial compression and valgus-varus bending. Anterior R-PHILOS produced lower EQV stress than other constructs under internal-external rotation and posterior bending. On the whole, R-PHILOS demonstrated a comparable fracture displacement to those LCP with anterior or anteromedial approaches, that achieved the lowest displacement values. In addition, the experimental mechanical test values shared a correlation with the FE model results. CONCLUSION: Overall, the anterior R-PHILOS was considered as a potential candidate for multifragmentary distal humeral shaft fractures. It demonstrated efficacious biomechanical performance in terms of implant stress and distal fragment displacement.


Assuntos
Fraturas do Úmero , Humanos , Fraturas do Úmero/diagnóstico por imagem , Fraturas do Úmero/cirurgia , Análise de Elementos Finitos , Fenômenos Biomecânicos , Úmero/diagnóstico por imagem , Úmero/cirurgia , Fixação Interna de Fraturas/métodos , Placas Ósseas
10.
Psychophysiology ; 61(4): e14479, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37920144

RESUMO

The locus coeruleus-norepinephrine (LC-NE) system, which regulates arousal levels, is important for cognitive control, including emotional conflict resolution. Additionally, the LC-NE system is implicated in P300 generation. If the P300 is mediated by the LC-NE system, and considering the established correlations between LC activity and pupil dilation, P300 amplitude should correlate with task-evoked (phasic) pupil dilation on a trial-by-trial basis. However, prior studies, predominantly utilizing oddball-type paradigms, have not demonstrated correlations between concurrently recorded task-evoked pupil dilation and P300 responses. Using a recently developed emotional face-word Stroop task that links pupil dilation to the LC-NE system, here, we examined both intra- and inter-individual correlations between task-evoked pupil dilation and P300 amplitude. We found that lower accuracy, slower reaction times, and larger task-evoked pupil dilation were obtained in the incongruent compared to the congruent condition. Furthermore, we observed intra-individual correlations between task-evoked pupil dilation and P300 amplitude, with larger pupil dilation correlating with a greater P300 amplitude. In contrast, pupil dilation did not exhibit consistent correlations with N450 and N170 amplitudes. Baseline (tonic) pupil size also showed correlations with P300 and N170 amplitudes, with smaller pupil size corresponding to larger amplitude. Moreover, inter-individual differences in task-evoked pupil dilation between the congruent and incongruent conditions correlated with differences in reaction time and P300 amplitude, though these effects only approached significance. To summarize, our study provides evidence for a connection between task-evoked pupil dilation and P300 amplitude at the single-trial level, suggesting the involvement of the LC-NE system in P300 generation.


Assuntos
Nível de Alerta , Pupila , Humanos , Teste de Stroop , Pupila/fisiologia , Tempo de Reação/fisiologia , Nível de Alerta/fisiologia , Locus Cerúleo/fisiologia , Norepinefrina/fisiologia
11.
Transfus Clin Biol ; 31(1): 36-40, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37944664

RESUMO

Hyperleukocytosis in leukemic patients may cause tumour lysis syndrome, disseminated intravascular coagulopathy, and leukostasis, resulting in decreased tissue perfusion and increasing the risk of mortality. Since the myeloid blasts are larger than lymphoid blasts and are less deformable, complications of leukostasis are seen more frequently in myeloid leukemia. Priapism is a less common complication associated with leukostasis in leukaemia patients that should be treated as soon as possible to avoid ischemic injuries. Although chemotherapeutic drugs such as hydroxyurea and imatinib are used to treat hyperleukocytosis in CML patients, leukocytapheresis (LCP) can achieve rapid cytoreduction. Prophylactic LCP could not offer any advantage over aggressive chemotherapy, but therapeutic leukocyte depletion has a proven role in patients having symptomatic leukostasis due to high tumour burden. Three patients with ischaemic priapism were reported at our institute's emergency department, where detumescence could not be achieved by distal shunting or aspiration with phenylephrine instillation. The procedure of therapeutic LCP was performed in all three patients on an emergency basis, which resolved painful priapism by rapid cytoreduction.


Assuntos
Leucemia Mieloide , Leucostasia , Priapismo , Masculino , Humanos , Priapismo/terapia , Priapismo/complicações , Leucaférese/métodos , Leucostasia/terapia , Leucostasia/complicações , Centros de Atenção Terciária
12.
Artigo em Inglês | MEDLINE | ID: mdl-37918461

RESUMO

The p38 mitogen-activated protein kinase (p38 MAPK) is a multifunctional molecule that is involved in cellular response to various stressful stimuli. In the present study, the full-length cDNA sequence of p38 MAPK (Lcp38 MAPK) was identified from the large yellow croaker Larimichthys crocea, which encoded a polypeptide of 361 amino acid residues. The predicted Lcp38 MAPK protein contained a highly conserved Thr-Gly-Tyr (TGY) motif, a glutamate and aspartate (ED) site, a substrate binding site (Ala-Thr-Arg-Trp < ATRW>), and a serine/threonine kinase catalytic (S_TKc) domain characteristic of the MAPK family. The constitutive expression of Lcp38 MAPK was detected in most of the tissues examined with the strongest expression in intestine. Subcellular localization in LCK cells (kidney cell line from a L. crocea) revealed that Lcp38 MAPK existed in both the cytoplasm and cell nucleus. The expression of Lcp38 MAPK after temperature stress was tested in LCK cells. The results indicated that Lcp38 MAPK transcripts were significantly upregulated under both cold (10 °C) and heat stress (35 °C) (P < 0.05). Furthermore, the phosphorylation levels of p38 MAPK as well the transcriptional levels of heat shock protein 27 (HSP27) and caspase3 in LCK cells were significantly induced under thermal exposure (P < 0.05). However, the cold- and heat induced HSP27 and caspase3 expression was significantly suppressed by SB203580, a specific inhibitor of p38-MAPK (P < 0.05). These findings indicated that Lcp38 MAPK might be involved in the cellular stress response via HSP27 and caspase3 in large yellow croaker.


Assuntos
Perciformes , Proteínas Quinases p38 Ativadas por Mitógeno , Animais , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas de Choque Térmico HSP27/metabolismo , Fosforilação , Temperatura , Perciformes/genética , Perciformes/metabolismo
13.
Pharmaceutics ; 15(12)2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38140040

RESUMO

The aim of the study is to develop a population pharmacokinetic (PopPK) model and to investigate the influence of CYP3A5/CYP3A4 and ABCB1 single nucleotide polymorphisms (SNPs) on the Tacrolimus PK parameters after LCP-Tac formulation in stable adult renal transplant patients. The model was developed, using NONMEM v7.5, from full PK profiles from a clinical study (n = 30) and trough concentrations (C0) from patient follow-up (n = 68). The PK profile of the LCP-Tac formulation was best described by a two-compartment model with linear elimination, parameterized in elimination (CL/F) and distributional (CLD/F) clearances and central compartment (Vc/F) and peripheral compartment (Vp/F) distribution volumes. A time-lagged first-order absorption process was characterized using transit compartment models. According to the structural part of the base model, the LCP-Tac showed an absorption profile characterized by two transit compartments and a mean transit time of 3.02 h. Inter-individual variability was associated with CL/F, Vc/F, and Vp/F. Adding inter-occasion variability (IOV) on CL/F caused a statistically significant reduction in the model minimum objective function MOFV (p < 0.001). Genetic polymorphism of CYP3A5 and a cluster of CYP3A4/A5 SNPs statistically significantly influenced Tac CL/F. In conclusion, a PopPK model was successfully developed for LCP-Tac formulation in stable renal transplant patients. CYP3A4/A5 SNPs as a combined cluster including three different phenotypes (high, intermediate, and poor metabolizers) was the most powerful covariate to describe part of the inter-individual variability associated with apparent elimination clearance. Considering this covariate in the initial dose estimation and during the therapeutic drug monitoring (TDM) would probably optimize Tac exposure attainments.

14.
Methods Enzymol ; 687: 31-48, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37666637

RESUMO

Structural studies of the ZIPs have greatly improved the understanding of the working mechanism for this functionally important metal transporter family. In this chapter, we describe the procedures to overexpress, purify, and crystallize a representative bacterial ZIP from Bordetella bronchiseptica (BbZIP), the structure of which was the first one that revealed the common structural framework of the transmembrane domain conserved within the entire ZIP family. We also discuss the considerations when we designed these experiments and compare the approaches used in this study with those commonly used in other works. The protocols provided in this chapter will facilitate structural and biochemical studies of other members of the ZIP family.


Assuntos
Bordetella bronchiseptica , Bordetella bronchiseptica/genética , Cristalização , Proteínas de Membrana Transportadoras , Metais , Domínios Proteicos
15.
Transpl Int ; 36: 11366, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37588007

RESUMO

LCP-tacrolimus displays enhanced oral bioavailability compared to immediate-release (IR-) tacrolimus. The ENVARSWITCH study aimed to compare tacrolimus AUC0-24 h in stable kidney (KTR) and liver transplant recipients (LTR) on IR-tacrolimus converted to LCP-tacrolimus, in order to re-evaluate the 1:0.7 dose ratio recommended in the context of a switch and the efficiency of the subsequent dose adjustment. Tacrolimus AUC0-24 h was obtained by Bayesian estimation based on three concentrations measured in dried blood spots before (V2), after the switch (V3), and after LCP-tacrolimus dose adjustment intended to reach the pre-switch AUC0-24 h (V4). AUC0-24 h estimates and distributions were compared using the bioequivalence rule for narrow therapeutic range drugs (Westlake 90% CI within 0.90-1.11). Fifty-three KTR and 48 LTR completed the study with no major deviation. AUC0-24 h bioequivalence was met in the entire population and in KTR between V2 and V4 and between V2 and V3. In LTR, the Westlake 90% CI was close to the acceptance limits between V2 and V4 (90% CI = [0.96-1.14]) and between V2 and V3 (90% CI = [0.96-1.15]). The 1:0.7 dose ratio is convenient for KTR but may be adjusted individually for LTR. The combination of DBS and Bayesian estimation for tacrolimus dose adjustment may help with reaching appropriate exposure to tacrolimus rapidly after a switch.


Assuntos
Rim , Tacrolimo , Humanos , Teorema de Bayes
16.
Materials (Basel) ; 16(15)2023 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-37570113

RESUMO

Proper fixation techniques are crucial in orthopedic surgery for the treatment of various medical conditions. Fractures of the distal humerus can occur due to either high-energy trauma with skin rupture or low-energy trauma in osteoporotic bone. The recommended surgical approach for treating these extra-articular distal humerus fractures involves performing an open reduction and internal fixation procedure using plate implants. This surgical intervention plays a crucial role in enhancing patient recovery and minimizing soft tissue complications. Dynamic Compression Plates (DCPs) and Locking Compression Plates (LCPs) are commonly used for bone fixation, with LCP extra-articular distal humerus plates being the preferred choice for extra-articular fractures. These fixation systems have anatomically shaped designs that provide angular stability to the bone. However, depending on the shape and position of the bone fracture, additional plate bending may be required during surgery. This can pose challenges such as increased surgery time and the risk of incorrect plate shaping. To enhance the accuracy of plate placement, the study introduces the Method of Anatomical Features (MAF) in conjunction with the Characteristic Product Features methodology (CPF). The utilization of the MAF enables the development of a parametric model for the contact surface between the plate and the humerus. This model is created using specialized Referential Geometrical Entities (RGEs), Constitutive Geometrical Entities (CGEs), and Regions of Interest (ROI) that are specific to the human humerus bone. By utilizing this anatomically tailored contact surface model, the standard plate model can be customized (bent) to precisely conform to the distinct shape of the patient's humerus bone during the pre-operative planning phase. Alternatively, the newly designed model can be fabricated using a specific manufacturing technology. This approach aims to improve geometrical accuracy of plate fixation, thus optimizing surgical outcomes and patient recovery.

17.
Animals (Basel) ; 13(16)2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37627343

RESUMO

Canine disc-associated cervical spondylomyelopathy (DA-CSM) is a form of caudal CSM, characterized by the compression of the spinal cord and nerve roots due to an intervertebral disc protrusion. It is more frequent in large canine breeds. A variety of surgical techniques has been proposed for DA-CSM. The aim of the study was to evaluate the outcomes of a cervical distraction-stabilization technique using an intervertebral anchored fusion device (C-LOX) combined with a locking compression plate (LCP plate) for the treatment of DA-CSM in dogs, based on clinical and radiographical follow-up data. Thirteen dogs affected by DA-CSM were included in the study. After the surgical procedure, an improvement in neurological status was documented in 9/13 cases. This cervical distraction-stabilization technique seems to be a valuable surgical alternative to treat this canine pathology.

18.
Front Microbiol ; 14: 1229396, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37469423

RESUMO

[This corrects the article DOI: 10.3389/fmicb.2021.788500.].

19.
Polymers (Basel) ; 15(14)2023 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-37514445

RESUMO

The applicability of a polyether ether ketone locking compression plate (PEEK LCP) fabricated using FDM (fused deposition modeling)-based 3D printing to treat actual patients was studied. Three different tests-bending, axial compression, and axial torsion-were conducted on tibial non-osteoporotic comminuted diaphyseal fracture samples fixed with the commercial titanium alloy LCP and 3D-printed PEEK LCP. Comparing the outcomes of these tests revealed that the commercial titanium alloy LCP underwent plastic deformation in the bending and axial torsion tests, though the LCP did not fail even when an external force greater than the maximum allowable load of the tibia fixture of the LCP was applied. Elastic deformation occurred in the 3D-printed PEEK LCP in the bending and axial torsion tests. However, deformation occurred even under a small external force, and its stiffness was 10% compared to commercial titanium alloy LCP. Thus, 3D-printed PEEK LCP can be applied to the fracture conditions in non-weight-bearing regions. The experimental results reveal detailed insights into the treatment of actual patients by considering the stiffness and high toughness of 3D-printed PEEK LCP.

20.
BMC Musculoskelet Disord ; 24(1): 612, 2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37491249

RESUMO

BACKGROUND: Many surgical treatment methods exist for clavicle shaft fractures. A locking compression plate (LCP) fixation with three screws per fracture side is commonly used. For certain fractures a stabilization with 2 screws per side is potentially suitable, offering the advantage of reduced soft tissue approach, while avoiding the disadvantages of minimally-invasive nailing at the same time. This hypothesis was evaluated biomechanically and clinically. METHODS: Four treatment procedures were investigated biomechanically using composite human clavicle specimens. A load-to-failure test was performed using a three-point cantilever test. In group 1, a simple shaft fracture was simulated and stabilized with 2 screws per fracture side (5-hole LCP). In the second group 3 screws per side (7-hole LCP) were used. In group 3, a non-reduced fracture zone was simulated and treated with 3 screws per side (7-hole LCP). In group 4, an anatomically reduced fracture zone was simulated and treated with 3 screws per side (7-hole LCP). Furthermore 27 patients treated with a short plate and 2 screws per side (similar to group 1) were assessed after a minimum follow-up of 12 months (Constant and DASH Score). RESULTS: The maximum load-to-failure of group 1 was 367N. We observed the highest load-to-failure in group 2 with 497N and the lowest in group 3 with 90N. In group 4 a maximum load-to-failure of 298N could be evaluated. There was no significant difference in load-to-failure between the treatment of a simple clavicle fracture using 5- or 7-hole LCP (p = 0.121). However, we found a significant difference of load-to-failure between the simple and anatomically reduced fracture using a 7-hole plate (p = 0.014). The mean constant score of the surgically treated patients was 95 and the DASH score 3.0. Fracture consolidation was observed in 96.3%. CONCLUSIONS: For certain non-fragmented and well interlocking 2-part fractures, a plate osteosynthesis fixed with only 2 screws per fracture side might offer sufficient biomechanical stability, better soft tissue preservation and comparable fusion rates compared to the operative treatment with 3 screws per side. However, the maximum load-to-failure of the 7-hole LCP was higher than of the 5-hole LCP, but this difference was not statistically significant. TRIAL REGISTRATION: Approval from the ethics committee of the Technical University of Dresden was retrospectively obtained (EK 588122019).


Assuntos
Clavícula , Fraturas Ósseas , Humanos , Clavícula/diagnóstico por imagem , Clavícula/cirurgia , Estudos Retrospectivos , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Fixação Interna de Fraturas/efeitos adversos , Fixação Interna de Fraturas/métodos , Placas Ósseas , Fenômenos Biomecânicos
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