ABSTRACT
OBJECTIVES: This study aimed to investigate bond performance of various resin luting cement (RLC) systems on enamel and dentin in different etching modes and to compare the RLC-tooth interface morphology using scanning electron microscopy (SEM). METHODS AND MATERIALS: The self-adhesive RLC systems used in combination with universal adhesives were as follows: Scotchbond Universal Adhesive Plus + RelyX Universal (3M Oral Care) and Clearfil Universal Bond Quick ER + SA Luting Multi (Kuraray Noritake Dental). These RLC systems were also used alone as self-adhesive RLC systems without universal adhesives (self-adhesive mode). The conventional RLC systems for comparison materials were as follows: BeautiBond Xtream + ResiCem EX (Shofu) and Tooth Primer + Panavia V5 (Kuraray Noritake Dental). Twelve specimens were prepared for each group to measure shear bond strength (SBS) in different etching modes. A stainless-steel rod was used as a substitute for indirect restorations. Bonded specimens were allocated to baseline (stored for 24 hours) and artificially aged (thermocycling [TC] for 10,000 cycles) groups. Representative treated tooth surfaces and RLC-tooth interfaces were observed using SEM. RESULTS: Three-way analysis of variance (ANOVA) revealed that all the factors (etching mode, storage period, and RLC system) had a significant influence on the enamel SBS values (p<0.05). Enamel SBS was significantly higher in etch-&-rinse (ER) mode than in self-etch (SE) mode, regardless of RLC system or storage period. Three-way ANOVA showed that all the factors had a significant influence on the dentin SBS values (p<0.001). Most RLC systems showed significantly higher dentin SBS in SE mode than in ER mode, regardless of storage period. However, the combination with Scotchbond Universal Adhesive Plus and RelyX Universal showed no significant difference in SBS values between etching modes at the baseline and showed a significantly higher SBS value in ER mode than in SE mode after TC. CONCLUSIONS: The self-adhesive RLC systems with universal adhesives tended to show higher enamel and dentin bond performance than the self-adhesive RLC systems alone. The morphology of treated tooth surfaces and resin cement-tooth interfaces were dependent on the RLC system and etching mode used. The RLC systems with primer application showed a thin, high-density layer above the intact dentin in both etching modes, suggesting chemical interaction.
Subject(s)
Dental Bonding , Resin Cements , Dental Cements/chemistry , Dentin-Bonding Agents/chemistry , Dental Bonding/methods , Dentin , Materials Testing , Shear StrengthABSTRACT
BACKGROUND: Data from the COVID-19 pandemic describes increases in drug use and related harms, especially fatal overdose. However, evidence is needed to better understand the pathways from pandemic-related factors to substance use behaviours. Thus, we investigated stockpiling drugs among people who use drugs (PWUD) in five cities in the United States and Canada. METHODS: We used data from two waves of interviews among participants in nine prospective cohorts to estimate the prevalence and correlates of stockpiling drugs in the previous month. Longitudinal correlates were identified using bivariate and multivariate generalized linear mixed-effects modeling analyses. RESULTS: From May 2020 to February 2021, we recruited 1873 individuals who completed 2242 interviews, of whom 217 (11.6%) reported stockpiling drugs in the last month at baseline. In the multivariate model, stockpiling drugs was significantly and positively associated with reporting being greatly impacted by COVID-19 (Adjusted Odds Ratio [AOR]= 1.21, 95% CI: 1.09-1.45), and at least daily use of methamphetamine (AOR = 4.67, 95% CI: 2.75-7.94) in the past month. CONCLUSIONS: We observed that approximately one-in-ten participants reported stocking up on drugs during the COVID-19 pandemic. This behaviour was associated with important drug-related risk factors including high-intensity methamphetamine use. While these correlations need further inquiry, it is possible that addressing the impact of COVID-19 on vulnerable PWUD could help limit drug stockpiling, which may lower rates of high-intensity stimulant use.
Subject(s)
COVID-19 , Drug Overdose , Methamphetamine , Humans , Prospective Studies , Pandemics , COVID-19/epidemiology , Drug Overdose/epidemiologyABSTRACT
OBJECTIVES: We previously reported, based on a multicenter randomized-control study, that the efficacy of intra-articular injections of hyaluronic acid (IA-HA) was not inferior to that of oral non-steroidal anti-inflammatory drugs (NSAIDs) in patients with knee osteoarthritis (OA). However, the molecular effects on the pathophysiology of knee OA remain unclear. C-terminal telopeptides of type II collagen (CTX-II) is reported to primarily originate from the interface between articular cartilage and subchondral bone, which is a site of potential remodeling in OA. We performed a predefined sub-analysis of the previous study to compare the changes of urinary CTX-II (uCTX-II) in response to IA-HA to those in response to NSAID for knee OA. DESIGN: A total of 200 knee OA patients were registered from 20 hospitals and randomized to receive IA-HA (2,700 kDa HA, 5 times at 1-week intervals) or NSAID (loxoprofen sodium, 180 mg/day) for 5 weeks. The uCTX-II levels were measured before and after treatment. RESULTS: The uCTX-II levels were significantly increased by IA-HA treatment (337.7 ± 193.8 to 370.7 ± 234.8 ng/µmol Cr) and were significantly reduced by NSAID treatment (423.2 ± 257.6 to 370.3 ± 250.9 ng/µmol Cr). The %changes of uCTX-II induced by IA-HA (11.6 ± 29.5%) and NSAID (-9.0 ± 26.7%) was significantly different (between-group difference: 20.6, 95% confidence intervals: 10.6 to 30.6). CONCLUSIONS: While both IA-HA and NSAID improved symptoms of knee OA, uCTX-II levels were increased by IA-HA and reduced by NSAIDs treatment, suggesting these treatments may improve symptoms of knee OA through different modes of action.
Subject(s)
Osteoarthritis, Knee , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Biomarkers , Collagen Type II , Humans , Hyaluronic Acid/therapeutic use , Injections, Intra-Articular , Molecular Weight , Treatment Outcome , Viscosupplements/therapeutic useABSTRACT
PURPOSE: To determine if responses given to each question of the Scoliosis Research Society-22 (SRS22), Oswestry disability index (ODI) and Short Form-36 (SF-36) questionnaires are influenced by the radiological parameters. METHODS: Patients enrolled in a multi-centre prospectively collected adult spinal deformity database who had complete SRS22, ODI and SF-36 data at baseline and at one-year follow-up were analysed. The presence of a differential item function of each question within each score in relation to radiological parameters was analysed using a mixed Rasch model with the radiological threshold value(s) determined. RESULTS: Of those patients analysed (n = 1745; 1406 female, average age 51.0 ± 19.8 years), 944 were surgically and 801 were non-surgically treated. For the SRS22, questions (Q) 3, 5 and 18 were sensitive to almost all radiological parameters and the overall score was found sensitive to the Cobb angle. For the ODI, Q3, 6, 9 and 10 were not sensitive to any radiologic parameters whereas Q4 and 5 were sensitive to most. In contrast, only 3 of the SF-36 items were sensitive to radiological parameters. CONCLUSIONS: 78% of the SRS-22, 60% of the ODI and 8% of the questions in the SF-36 are sensitive to radiological parameters. Sagittal imbalance is independently associated with a poor overall outcome, but affects mental status and function more than pain and self-image. The assembly of questions responsive to radiological parameters may be useful in establishing a connection between changes in radiologic parameters and HRQL.
Subject(s)
Quality of Life , Scoliosis , Adult , Aged , Databases, Factual , Disability Evaluation , Female , Humans , Middle Aged , Retrospective Studies , Scoliosis/diagnostic imaging , Scoliosis/surgery , Surveys and Questionnaires , Treatment OutcomeABSTRACT
We present the architecture of the versatile nuclear magnetic resonance (NMR) spectrometer with software-defined radio technology and its application to the dynamically controlled pulsed magnetic fields. The pulse-field technology is the only solution to access magnetic fields greater than 50 T, but the NMR experiment in the pulsed magnetic field was difficult because of the continuously changing field strength. The dynamically controlled field pulse allows us to perform NMR experiment in a quasi-steady field condition by creating a constant magnetic field for a short time around the peak of the field pulse. We confirmed the reproducibility of the field pulses using the NMR spectroscopy as a high precision magnetometer. With the highly reproducible field strength, we succeeded in measuring the nuclear spin-lattice relaxation rate 1/T1, which had never been measured by the pulse-field NMR experiment without dynamic field control. We also implement the NMR spectrum measurement with both the frequency-sweep and field-sweep modes and discuss the appropriate choices of these modes depending on the magnetic properties of the sample to be measured. This development, with further improvement at a long-duration field pulse, will innovate the microscopic measurement in extremely high magnetic fields.
ABSTRACT
Background Although immunotherapy is thought to be a promising cancer treatment, most patients do not respond to immunotherapy. In this post hoc analysis of a phase 1/2 study, associations of programmed death ligand 1 (PD-L1), PD-L2, and HLA class I expressions with responses to dendritic cells (DCs)-based immunotherapy were investigated in patients with advanced sarcoma. Methods This study enrolled 35 patients with metastatic and/or recurrent sarcomas who underwent DC-based immunotherapy. The associations of PD-L1, PD-L2, and HLA class I expressions in tumor specimens, which were resected before immunotherapy, with immune responses (increases of IFN-γ and IL-12) and oncological outcomes were evaluated. Results Patients who were PD-L2 (+) showed lower increases of IFN-γ and IL-12 after DC-based immunotherapy than patients who were PD-L2 (−). The disease control (partial response or stable disease) rates of patients who were PD-L1 (+) and PD-L1 (−) were 0% and 22%, respectively. Disease control rates of patients who were PD-L2 (+) and PD-L2 (−) were 13% and 22%, respectively. Patients who were PD-L1 (+) tumors had significantly poorer overall survival compared with patients who were PD-L1 (−). No associations of HLA class I expression with the immune response or oncological outcomes were observed. Conclusions This study suggests that PD-L1 and PD-L2 are promising biomarkers of DC-based immunotherapy, and that addition of immune checkpoint inhibitors to DC-based immunotherapy may improve the outcomes of DC-based immunotherapy (AU)
Subject(s)
Humans , Male , Female , Adult , B7-H1 Antigen/metabolism , Histocompatibility Antigens Class I/metabolism , Antineoplastic Agents, Immunological , Sarcoma/therapy , Dendritic Cells , Biomarkers, Tumor , Sarcoma/immunology , Sarcoma/pathology , Treatment OutcomeABSTRACT
Across Far East Asia, aspermic Fasciola forms are found endemically. They have abnormal spermatogenesis and oogenesis, and it is presumed that their progeny are produced parthenogenetically and clonally. Because of this, they are also termed parthenogenic Fasciola forms. Currently, there is no evidence that they do indeed reproduce parthenogenetically and clonally. In this study, the multilocus genetic type (MLG) in 12 microsatellite markers of adult flukes and their subsequent progeny larvae were analysed using two laboratory aspermic Fasciola triploid strains. The MLGs of adults and their larvae were identical for all markers evaluated, suggesting that these strains reproduce their progeny clonally. The deviation between theoretical and actual frequency within the larvae genotype of the Fh_6 locus resulted in the inability for self-fertilization within individual adult flukes. These findings strongly suggested that aspermic Fasciola forms reproduce their progeny by means of parthenogenesis, possibly gynogenesis.
Subject(s)
Fasciola , Animals , Asia , Asia, Eastern , Haplotypes , Male , NADH Dehydrogenase/genetics , ParthenogenesisABSTRACT
The ongoing mass extinction of animal species at an unprecedented rate is largely caused by human activities. Progressive habitat destruction and fragmentation is resulting in accelerated loss of biodiversity on a global scale. Over decades, captive breeding programs of non-domestic species were characterized by efforts to optimize species-specific husbandry, to increase studbook-based animal exchange, and to improve enclosure designs. To counter the ongoing dramatic loss of biodiversity, new approaches are warranted. Recently, new ideas, particularly the application of assisted reproduction technologies (ART), have been incorporated into classical zoo breeding programs. These technologies include semen and oocyte collection, artificial insemination, and in-vitro embryo generation. More futuristic ideas of advanced ART (aART) implement recent advances in biotechnology and stem-cell related approaches such as cloning, inner cell mass transfer (ICM), and the stem-cell-associated techniques (SCAT) for the generation of gametes and ultimately embryos of highly endangered species, such as the northern white rhinoceros (Ceratotherium simum cottoni) of which only two female individuals are left. Both, ART and aART greatly depend on and benefit from the rapidly evolving cryopreservation techniques and biobanking not only of genetic, but also of viable cellular materials suitable for the generation of induced pluripotent stem cells (iPSC). The availability of cryopreserved materials bridges gaps in time and space, thereby optimizing the available genetic variability and enhancing the chance to restore viable populations.
Subject(s)
Biological Specimen Banks , Endangered Species , Animals , Biodiversity , Female , Perissodactyla , Reproductive Techniques, Assisted/veterinaryABSTRACT
PURPOSE: Objectives in scoliosis corrective surgery include restoration of normal sagittal and coronal parameters to achieve patient satisfaction. HRQLs improvements remain limited after corrective surgery. The aim of this study was to evaluate the HRQL subclass variability specific to the sagittal and coronal correction in adult scoliosis surgery. METHODS: This multi-centre prospective analysis of consecutive adult spinal deformity (ASD) patients, from five European centres, only included multilevel instrumentation for scoliosis. d-(delta) values for each parameter represented pre to post-operative changes. Parameters included demographics, baseline, 1- and 2-year. HRQL outcomes (Oswestry disability index (ODI), Scoliosis Research Society (SRS)-22 and Short Form (SF36)), sagittal correction including relative spinopelvic alignment (dRSA) and coronal correction including major Cobb (dCobb) angles. RESULTS: A total of 353 patients reached 1-year and 2-year follow up. All HRQL total scores significantly improved postoperatively, including ODI, SRS-22 and SF36. HRQL subclasses which displayed persistent improvements correlated to dRSA included sex-life, self-image, fatigue, vitality, social functioning. The only HRQL subclass improvement that correlated with dCobb was self-image. CONCLUSION: Adult scoliosis surgery improves overall HRQL, having a minimal effect on each variable. Importantly, greater coronal deformity correction affects only greater self-image scores, whereas with greater sagittal correction there are many greater HRQL sub-class impacts. Correction and restoration of coronal balance is one of the surgical goals in adult scoliosis but the degree to which Cobb angle is corrected, apart from self-image, does not correlate with gains in sub-classes of HRQL. These results need to be taken into account when planning surgery.
Subject(s)
Quality of Life , Scoliosis , Adult , Follow-Up Studies , Humans , Prospective Studies , Retrospective Studies , Scoliosis/diagnostic imaging , Scoliosis/surgery , Treatment OutcomeABSTRACT
PURPOSE: To evaluate the pain and functional effect of the COVID-19 pandemic on patients with ASD reflected by their response to SRS-22, ODI, and SF-36 questionnaires. METHODS: Patients who had stable pain and functional outcome scores over the preceding 2 years were enrolled in a local prospectively collected adult spinal deformity (ASD) database. A reanalysis of their SRS22, ODI and SF-36 data 14 days into confinement were compared to their last pre-confinement scores. RESULTS: 89 patients were included in this study (average age 60.7 years, 91% female) with an average time from last FU until confinement of 9.6 months. The ODI total score worsened by 5 points post-confinement with no difference seen in personal care, walking and social life. In contrast, the SRS-22 score showed small improvements in function/activity and satisfaction, but no significant differences for the other domains. Similarly, the SF-36 showed small improvements in physical function, physical and emotional role, vitality and PCS. CONCLUSION: The global COVID-19 pandemic and ensuing confinement had variable overall effects on ASD patients, without the expected marked worsening. In addition, this study illustrates that the SRS-22 questionnaire is less influenced by environmental and psychological factors than the ODI supporting its objectivity and accuracy in the evaluation of the QoL of ASD patients.
Subject(s)
COVID-19 , Pain/etiology , Quality of Life , Spinal Curvatures/complications , Female , Humans , Male , Middle Aged , Pain/epidemiology , Self ReportABSTRACT
BACKGROUND: Although immunotherapy is thought to be a promising cancer treatment, most patients do not respond to immunotherapy. In this post hoc analysis of a phase 1/2 study, associations of programmed death ligand 1 (PD-L1), PD-L2, and HLA class I expressions with responses to dendritic cells (DCs)-based immunotherapy were investigated in patients with advanced sarcoma. METHODS: This study enrolled 35 patients with metastatic and/or recurrent sarcomas who underwent DC-based immunotherapy. The associations of PD-L1, PD-L2, and HLA class I expressions in tumor specimens, which were resected before immunotherapy, with immune responses (increases of IFN-γ and IL-12) and oncological outcomes were evaluated. RESULTS: Patients who were PD-L2 (+) showed lower increases of IFN-γ and IL-12 after DC-based immunotherapy than patients who were PD-L2 (-). The disease control (partial response or stable disease) rates of patients who were PD-L1 (+) and PD-L1 (-) were 0% and 22%, respectively. Disease control rates of patients who were PD-L2 (+) and PD-L2 (-) were 13% and 22%, respectively. Patients who were PD-L1 (+) tumors had significantly poorer overall survival compared with patients who were PD-L1 (-). No associations of HLA class I expression with the immune response or oncological outcomes were observed. CONCLUSIONS: This study suggests that PD-L1 and PD-L2 are promising biomarkers of DC-based immunotherapy, and that addition of immune checkpoint inhibitors to DC-based immunotherapy may improve the outcomes of DC-based immunotherapy.
Subject(s)
B7-H1 Antigen/metabolism , Histocompatibility Antigens Class I/metabolism , Immunotherapy , Programmed Cell Death 1 Ligand 2 Protein/metabolism , Sarcoma/therapy , Adult , Biomarkers, Tumor/metabolism , Dendritic Cells , Female , Humans , Interferon-gamma/metabolism , Interleukin-12/metabolism , Male , Sarcoma/immunology , Sarcoma/mortality , Sarcoma/pathology , Treatment OutcomeABSTRACT
Induction of tumor cell death is the therapeutic goal for most anticancer drugs. Yet, a mode of drug-induced cell death, known as immunogenic cell death (ICD), can propagate antitumoral immunity to augment therapeutic efficacy. Currently, the molecular hallmark of ICD features the release of damage-associated molecular patterns (DAMPs) by dying cancer cells. Here, we show that gemcitabine, a standard chemotherapy for various solid tumors, triggers hallmark immunostimualtory DAMP release (e.g., calreticulin, HSP70, and HMGB1); however, is unable to induce ICD. Mechanistic studies reveal gemcitabine concurrently triggers prostaglandin E2 release as an inhibitory DAMP to counterpoise the adjuvanticity of immunostimulatory DAMPs. Pharmacological blockade of prostaglandin E2 biosythesis favors CD103+ dendritic cell activation that primes a Tc1-polarized CD8+ T cell response to bolster tumor rejection. Herein, we postulate that an intricate balance between immunostimulatory and inhibitory DAMPs could determine the outcome of drug-induced ICD and pose COX-2/prostaglandin E2 blockade as a strategy to harness ICD.
Subject(s)
Alarmins/metabolism , Antineoplastic Agents/pharmacology , Dinoprostone/metabolism , Immunogenic Cell Death/drug effects , Animals , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Calreticulin/metabolism , Cell Line, Tumor , Cisplatin/pharmacology , Deoxycytidine/analogs & derivatives , Deoxycytidine/pharmacology , HMGB1 Protein/metabolism , Humans , Immunization/methods , Mice, Inbred C57BL , GemcitabineABSTRACT
The effects of exercise on mechanical hyperalgesia, joint contracture, and muscle injury resulting from immobilization are not completely understood. This study aimed to investigate the effects of cyclic stretching on these parameters in a rat model of chronic post-cast pain (CPCP). Seventeen 8-week-old Wistar rats were randomly assigned to (1) control group, (2) immobilization (CPCP) group, or (3) immobilization and stretching exercise (CPCP+STR) group. In the CPCP and CPCP+STR groups, both hindlimbs of each rat were immobilized in full plantar flexion with a plaster cast for a 4-week period. In the CPCP+STR group, cyclic stretching exercise was performed 6 days/week for 2 weeks, beginning immediately after cast removal prior to reloading. Although mechanical hyperalgesia in the plantar skin and calf muscle, ankle joint contracture, and gastrocnemius muscle injury were observed in both immobilized groups, these changes were significantly less severe in the CPCP+STR group than in the CPCP group. These results clearly demonstrate the beneficial effect of cyclic stretching exercises on widespread mechanical hyperalgesia, joint contracture, and muscle injury in a rat model of CPCP.
Subject(s)
Chronic Pain/rehabilitation , Contracture/rehabilitation , Hyperalgesia/rehabilitation , Muscle, Skeletal/physiology , Physical Conditioning, Animal/methods , Animals , Casts, Surgical , Chronic Pain/etiology , Chronic Pain/pathology , Contracture/etiology , Contracture/pathology , Disease Models, Animal , Humans , Hyperalgesia/etiology , Hyperalgesia/pathology , Immobilization , Male , Rats , Rats, WistarABSTRACT
OBJECTIVE: Although the characteristics of electroencephalograms (EEGs) have been reported to change with age, anaesthesia-dependent oscillatory features and reactivity of the super-elderly EEG to anaesthesia have not been examined in detail. METHODS: Participants comprised 20 super-elderly patients (age; mean⯱â¯standard deviation, 87.1⯱â¯3.8â¯years) and 20 young adult patients (35.5⯱â¯8.5â¯years). At three levels of sevoflurane anaesthesia (minimum alveolar concentration [MAC] of 0.3, 0.7, and 1.4), oscillatory features of the frontal EEG were examined by analysing quadratic phase coupling (bicoherence) and power spectrum in α and δ-θ areas and compared in an anaesthesia-dependent manner, using the Friedman test. RESULTS: Among super-elderly individuals, bicoherences in the δ-θ area showed anaesthesia-dependent increases (median [interquartile range], 12.9% [5.2%], 19.2% [9.1%], 23.3% [8.7%]; 0.3, 0.7, 1.4 MAC sevoflurane, pâ¯=â¯0.000), whereas bicoherence in the α area did not change at these different anaesthesia levels (11.2% [3.9%], 12.5% [4.4%], 14.1% [5.7%], respectively; pâ¯=â¯0.142), counter to the results found in young adult patients, where both δ-θ and α bicoherences changed with anaesthesia. CONCLUSIONS: In the super-elderly, δ-θ bicoherence of EEG shows anaesthesia- dependent changes, whereas α activity remains small irrespective of anaesthesia level. SIGNIFICANCE: Quantification of δ-θ bicoherence is a candidate for anaesthesia monitoring in the super-elderly.
Subject(s)
Anesthetics, Inhalation/administration & dosage , Brain Waves/drug effects , Brain/drug effects , Sevoflurane/administration & dosage , Aged, 80 and over , Brain/physiology , Brain Waves/physiology , Electroencephalography , Female , Humans , MaleABSTRACT
BACKGROUND: Reduced expression of cluster of differentiation (CD) 133 and cyclo-oxygenase (COX) 2, and increased density of CD8+ tumour-infiltrating lymphocytes, are associated with a favourable tumour response to preoperative chemoradiotherapy (CRT). This study aimed to evaluate these markers in relation to tumour response after preoperative CRT in two rectal cancer cohorts. METHODS: Patients with low rectal cancer who underwent radical resection and preoperative short-term CRT in 2001-2007 (retrospective cohort) and long-term CRT in 2011-2017 (prospective cohort) were analysed. Pretreatment biopsies were stained immunohistochemically using antibodies to determine CD133 and COX-2 expression, and increased CD8+ density. Outcome measures were tumour regression grade (TRG), tumour downstaging and survival. RESULTS: For 95 patients in the retrospective cohort, the incidence of TRG 3-4 was 67 per cent when two or three immunohistochemistry (IHC) features were present, but only 20 per cent when there were fewer features (P < 0·001). The incidence of tumour downstaging was higher in patients with at least two IHC features (43 versus 22 per cent with fewer features; P = 0·029). The 49 patients in the prospective cohort had similar rates to those in the retrospective cohort (TRG 3-4: 76 per cent for two or more IHC features versus 25 per cent with fewer features, P < 0·001; tumour downstaging: 57 versus 25 per cent respectively, P = 0·022). Local recurrence-free survival rates in patients with more or fewer IHC features were similar in the retrospective and prospective cohort (P = 0·058 and P = 0·387 respectively). CONCLUSION: Assessment of CD133, COX-2 and CD8 could be useful in predicting a good response to preoperative CRT in patients with lower rectal cancer undergoing neoadjuvant therapy. Further studies are needed to validate the results in larger cohorts and investigate a survival benefit.
ANTECEDENTES: La expresión reducida de CD133 and COX-2, y un aumento en la densidad de los linfocitos infiltrantes del tumor CD8+ se han asociado recientemente con una respuesta favorable del tumor a la quimiorradioterapia preoperatoria (preoperative chemoradiotherapy, CRT). Este estudio evaluó estos marcadores respecto a la respuesta del tumor tras CRT preoperatoria en dos cohortes de cáncer colorrectal. MÉTODOS: Se analizaron pacientes con cáncer de recto bajo sometidos a resección radical y CRT preoperatoria de corta duración entre 2001-2007 (cohorte retrospectiva) y CRT de larga duración entre 2011-2017 (cohorte prospectiva). Se realizó tinción inmunohistoquímica (immunohistochemical, IHC) con anticuerpos para CD133, COX-2 y CD8 en las biopsias previas al tratamiento. Las características de interés incluyeron la disminución en las expresiones de CD133 y COX-2, y la densidad aumentada de CD8+. Las variables de interés fueron los grados de regresión tumoral (tumour regression grades, TRG) de acuerdo con Rödel, la reducción del estadio tumoral y las supervivencias. RESULTADOS: La cohorte retrospectiva incluyó 95 pacientes. En este subgrupo, la incidencia de TRGs 3-4 fue del 66,7% en pacientes con dos o tres características de la IHC, mientras que solo fue del 20,0% en pacientes con ninguna o con una característica (P < 0,001). Además, la incidencia de disminución del estadio tumoral fue más alta en pacientes que mostraban al menos dos características IHC (43,3%) que en los controles (21,5%; P = 0,029). En la cohorte prospectiva se incluyeron 49 pacientes y la incidencia de estos hallazgos fue similar (TRG 3-4, 76,2% en ≥ 2 características IHC versus 25,0% en los controles, P < 0,001; disminución del estadio tumoral, 57,1% en ≥ 2 características IHC versus 25,0% en los controles, P = 0,022). La supervivencia libre de recidiva local fue similar en las cohortes retrospectiva y prospectiva, cuando se compararon subgrupos de acuerdo con las características IHC (P = 0,058 y 0,387, respectivamente) CONCLUSIÓN: Este estudio sugiere que la evaluación de CD133, COX-2 y CD8 podría ser útil para la predicción de una buena respuesta a la CRT preoperatoria en pacientes con cáncer de recto bajo sometidos a tratamiento neoadyuvante. Se necesitan estudios adicionales para validar los resultados en amplias cohortes e investigar el beneficio en la supervivencia.
Subject(s)
Chemoradiotherapy, Adjuvant/methods , Lymphocytes, Tumor-Infiltrating/immunology , Rectal Neoplasms/immunology , Rectal Neoplasms/therapy , AC133 Antigen/immunology , Aged , Antigens, Neoplasm/immunology , CD8-Positive T-Lymphocytes/immunology , Cyclooxygenase 2/immunology , Disease-Free Survival , Female , Humans , Immunohistochemistry , Japan , Lymphocytes, Tumor-Infiltrating/metabolism , Male , Middle Aged , Neoadjuvant Therapy/methods , Predictive Value of Tests , Prospective Studies , Rectal Neoplasms/metabolism , Rectal Neoplasms/mortality , Retrospective Studies , Treatment OutcomeABSTRACT
OBJECTIVE: The objective of this study was to evaluate the chronic damage associated with pregnancies before and after the diagnosis of systemic lupus erythematosus (SLE). METHODS: Using childbearing-aged female SLE patient data registered at the Okayama and Showa University Hospitals, a nested case-control analysis was performed to investigate the relationship between pregnancy and chronic damage using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). RESULTS: Pregnancy occurred in 22 patients before and 13 patients after the diagnosis of SLE in 104 eligible patients. Live births occurred in 82% (33/40) and 50% (9/18) of the pregnancies before and after the diagnosis of SLE, respectively. After matching age and disease duration, 33 case patients with chronic damage (SDI ≥ 1) and 33 control patients without chronic damage (SDI = 0) were selected. Hypertension was more frequent in cases than in controls (48% vs. 24%, p = 0.041). Pregnancies before and after the diagnosis of SLE were comparable between cases and controls (before the diagnosis: nine case patients and eight control patients; after the diagnosis: three case patients and five control patients; p = 1.00). Even after adjusting for hypertension using multivariate analysis, the pregnancies before and after the diagnosis were not significant predictors for chronic damage (odds ratio = 1.48 (95% confidence interval 0.33-6.65)), p = 0.60 of the pregnancy before the diagnosis; odds ratio = 0.78 (95% confidence interval 0.13-4.74), p = 0.78 of the pregnancy after the diagnosis). CONCLUSION: Pregnancies, either before or after the diagnosis of SLE, did not show any differences in chronic damage. Our results help alleviate fears regarding childbearing in female patients with SLE and their families.
Subject(s)
Health Status , Lupus Erythematosus, Systemic/physiopathology , Pregnancy Complications , Adult , Case-Control Studies , Cross-Sectional Studies , Female , Humans , Japan , Logistic Models , Lupus Erythematosus, Systemic/diagnosis , Multivariate Analysis , Pregnancy , Registries , Severity of Illness Index , Young AdultABSTRACT
Dynamic mechanical analysis experiments were carried out to investigate the mechanical properties of four types of chemically different epoxy resins. Pressure-volume-temperature (PVT) experiments were performed to determine the free-volume hole fraction (hPVT) of each epoxy resin using the Simha-Somcynsky lattice-hole theory. Using the Williams-Landel-Ferry equation, the correlations between the relative hole fraction (1 - hPVTTr/hPVT, where hPVTTr is the hole fraction at a reference temperature Tr) and four typical parameters reflecting dynamic mechanical properties [storage modulus (E'), loss modulus (Eâ³), damping factor (tanδ), and complex viscosity (|η*|)] were studied in the temperature range from Tg(PVT) (the glass transition temperature determined by PVT data) to Tg(PVT) + 100 °C. In the temperature range from Tg(Eonset') (temperature corresponding to the intersection of the two tangent fitting lines in the E'(T) curve indicating the glassy-state and glass-transition stages) to Tg(PVT) + 100 °C, the variations in the four dynamic mechanical parameters with a relative hole fraction could be separated into two distinct categories: (i) log[E'(T)] and log[|η*|(T)] decreased linearly to their minimum values and then remained nearly unchanged with increasing relative hole fraction, and (ii) log[Eâ³(T)] and log[tanδ(T)] first increased monotonically to their maximum values and then decreased linearly with the increasing relative hole fraction. This study demonstrates that the PVT technique is a feasible and reliable experimental method to determine the hole fractions of thermoset polymers.
ABSTRACT
BACKGROUND: The metastatic involvement of regional lymph nodes is the most important prognostic factor for overall survival of skin cancer patients. The sonographic technique of freehand real-time tissue elastography (RTE), which displays tissue rigidity as a colour overlay of the tissue image, was developed. OBJECTIVE: Our purpose was to evaluate the benefit of RTE for detecting lymph node metastases of skin cancer non-invasively before operation. METHODS: We first selected lymph nodes of skin cancer patients which had already been diagnosed by biopsy as being reactive or metastatic, and then retrospectively collected images of RTE and B-mode and colour Doppler ultrasound on those lymph nodes performed preoperatively. Twenty-one lymph nodes from 12 patients with squamous cell carcinoma (SCC), 23 lymph nodes from 14 patients with malignant melanoma (MM) and 14 lymph nodes from six patients with extramammary Paget disease (Paget) were investigated. Elastographic images were assessed on a scale of one to four according to the percentage of high elasticity (hard) area (HEA) in the lymph node. RESULTS: In all three skin cancers, lymph nodes evaluated as grade 3 or 4 by RTE were metastatic. All lymph nodes evaluated as grade 1 or 2 by RTE were reactive in SCC, whereas some lymph nodes evaluated as grade 1 or 2 were metastatic in MM and Paget. CONCLUSION: Real-time tissue elastography may aid in distinguishing reactive lymph nodes from metastatic ones especially in SCC.