ABSTRACT
AIMS: This study examined whether patterns of post-mastectomy radiotherapy (PMRT) among women with early invasive breast cancer (EIBC) varied within England and Wales and explored the role of different patient factors in explaining any variation. MATERIALS AND METHODS: The study used national cancer data on women aged ≥50 years diagnosed with EIBC (stage I-IIIa) in England and Wales between January 2014 and December 2018 who had a mastectomy within 12 months of diagnosis. A multilevel mixed-effects logistic regression model was used to calculate risk-adjusted rates of PMRT for geographical regions and National Health Service acute care organisations. The study examined the variation in these rates within subgroups of women with different risks of recurrence (low: T1-2N0; intermediate: T3N0/T1-2N1; high: T1-2N2/T3N1-2) and investigated whether the variation was linked to patient case-mix within regions and organisations. RESULTS: Among 26 228 women, use of PMRT increased with greater recurrence risk (low: 15.0%; intermediate: 59.4%; high: 85.1%). In all risk groups, use of PMRT was more common among women who had received chemotherapy and decreased among women aged ≥80 years. There was weak or no evidence of an association between use of PMRT and comorbidity or frailty, for each risk group. In women with an intermediate risk, unadjusted rates of PMRT varied substantially between geographical regions (range 40.3-77.3%), but varied less for the high-risk (range 77.1-91.6%) and low-risk groups (range 4.1-32.9%). Adjusting for patient case-mix reduced the variation in regional and organisational PMRT rates to a small degree. CONCLUSIONS: Rates of PMRT are consistently high across England and Wales among women with high-risk EIBC, but variation exists across regions and organisations for women with intermediate-risk EIBC. Effort is required to reduce unwarranted variation in practice for intermediate-risk EIBC.
Subject(s)
Breast Neoplasms , Frailty , Female , Humans , Breast Neoplasms/epidemiology , Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Cohort Studies , England/epidemiology , Mastectomy , State Medicine , Wales/epidemiology , Middle AgedABSTRACT
PURPOSE: The da Vinci SP® (dVSP) surgical system (Intuitive Surgical, Sunnyvale, CA, USA), a robotic platform designed for single-incision surgery, overcame the need for multiple ports in traditional robotic surgery and issues including triangulation and retraction in single-incision laparoscopic surgery. However, previous studies only included case reports or series with small sample sizes. The aim of this study was to assess the safety and performance of the dVSP surgical system and its instruments and accessories for colorectal procedures. METHODS: The medical records of patients who had surgery with the dVSP from March 2019 to September 2021 at Ewha Womans University Seoul Hospital were investigated. The pathologic and follow-up data of patients who had malignant tumors were analyzed separately to evaluate oncological safety. RESULTS: Fifty patients (26 male and 24 female) with a median age of 59 years (interquartile range 52.5-63.0 years) were enrolled. The procedures included low anterior resection with total mesorectal excision (n = 16), sigmoid colectomy with complete mesocolic excision and central vessel ligation (CME + CVL) (n = 14), right colectomy with CME + CVL (n = 9), left colectomy with CME + CVL (n = 4), right colectomy (n = 6), and sigmoid colectomy (n = 1). Operative time significantly decreased after 25 cases (early phase vs. late phase; operative time 295.0 min vs. 250.0 min, p = 0.015; docking time 16.0 min vs. 12.0 min, p = 0.001; console time 212.0 min vs. 190.0 min, p = 0.019). Planned procedures were successfully completed in all patients. Postoperative outcomes were acceptable with only six cases of mild adverse events through a 3-month follow-up. No local recurrence and only one case of systemic recurrence occurred within 1 year postoperatively. CONCLUSIONS: This study demonstrated the surgical and oncological safety and feasibility of dVSP, which may be a novel surgical platform for colorectal surgery.
Subject(s)
Colorectal Surgery , Laparoscopy , Robotic Surgical Procedures , Robotics , Humans , Male , Female , Middle Aged , Robotic Surgical Procedures/methods , Robotics/methods , Colectomy/methods , Operative Time , Retrospective StudiesABSTRACT
AIMS: Clinical trials of post-mastectomy radiotherapy (PMRT) for early invasive breast cancer (EIBC) have included few older women. This study examined whether the association between overall survival or breast cancer-specific survival (BCSS) and receipt of PMRT for EIBC altered with age. MATERIALS AND METHODS: The study used patient-level linked cancer registration, routine hospital and radiotherapy data for England and Wales. It included 31 243 women aged ≥50 years diagnosed between 2014 and 2018 with low- (T1-2N0), intermediate- (T3N0/T1-2N1) or high-risk (T1-2N2/T3N1-2) EIBC who received a mastectomy within 12 months from diagnosis. Patterns of survival were analysed using a landmark approach. Associations between overall survival/BCSS and PMRT in each risk group were analysed with flexible parametric survival models, which included patient and tumour factors; whether the association between PMRT and overall survival/BCSS varied by age was assessed using interaction terms. RESULTS: Among 4711 women with high-risk EIBC, 86% had PMRT. Five-year overall survival was 70.5% and BCSS was 79.3%. Receipt of PMRT was associated with improved overall survival [adjusted hazard ratio (aHR) 0.75, 95% confidence interval 0.64-0.87] and BCSS (aHR 0.78, 95% confidence interval 0.65-0.95) compared with women who did not have PMRT; associations did not vary by age (overall survival, P-value for interaction term = 0.141; BCSS, P = 0.077). Among 10 814 women with intermediate-risk EIBC, 59% had PMRT; 5-year overall survival was 78.4% and BCSS was 88.0%. No association was found between overall survival (aHR 1.01, 95% confidence interval 0.92-1.11) or BCSS (aHR 1.16, 95% confidence interval 1.01-1.32) and PMRT. There was statistical evidence of a small change in the association with age for overall survival (P = 0.007), although differences in relative survival were minimal, but not for BCSS (P = 0.362). CONCLUSIONS: The association between PMRT and overall survival/BCSS does not appear to be modified by age among women with high- or intermediate-risk EIBC and, thus, treatment recommendations should not be modified on the basis of age alone.
Subject(s)
Breast Neoplasms , Female , Humans , Aged , Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Mastectomy , Cohort Studies , Radiotherapy, Adjuvant , Neoplasm Staging , Retrospective StudiesABSTRACT
To assess the range and frequency of additional congenital malformations identified among children born alive with CL/P.Analysis of patient-level data from a national registry of cleft births linked to national administrative data of hospital admissions.National Health Service, England.Children born between 2000 and 2012 receiving cleft care in English NHS hospitals.The proportion of children with ICD-10 codes for additional congenital malformations, according to cleft type.The study included 9403 children. Of these 2114 (22.5%) had CL±A, 4509 (48.0%) had CP, 1896 (20.2%) had UCLP, and 884 (9.4%) had BCLP. A total of 3653 (38.8%) children had additional congenital malformations documented in their hospital admission records. The prevalence of additional congenital malformations was greatest among children with CP (53.0%), followed by those with BCLP (33.5%), UCLP (26.3%), and then CL±A (22.2%) (P < .001). Among those with UCLP, children with right-sided clefts were more likely to have additional malformations than those with left-sided clefts (31.6% vs 23.0%, P < .001). Malformations of the skeletal system and circulatory system were most common, affecting 10.5% and 10.2% of the included children, respectively. A total of 16.8% of children had additional congenital malformations affecting 2 or more structural systems.Congenital malformations are common among children born alive with a cleft, affecting over half of some cleft subgroups. Given the frequency of certain structural malformations, clinicians should consider standardized screening for these children. Establishing good links with pediatric and genetic services is recommended.
Subject(s)
Cleft Lip , Cleft Palate , Child , Humans , Cleft Lip/epidemiology , Cleft Lip/genetics , State Medicine , Cleft Palate/epidemiology , Cleft Palate/genetics , HospitalizationABSTRACT
Dysphagia in people with advanced oesophageal cancer can be treated by oesophageal stents, external beam radiotherapy (EBRT) and intraluminal brachytherapy. Despite guidelines recommending brachytherapy for patients with a predicted life expectancy exceeding 3 months, its uptake in the UK has been limited. Here we examine the strength of the evidence supporting the use of brachytherapy compared with oesophageal stents and EBRT and possible reasons for its limited uptake. Trials and observational studies suggest brachytherapy alone confers a benefit to patients, but its impact is less immediate than oesophageal stents; the evidence on effectiveness and value-for-money is limited. Moreover, stronger evidence will probably be insufficient to increase uptake, due to the extra complexity of delivery compared with stents and EBRT and a lack of experience among specialists.
Subject(s)
Brachytherapy/methods , Deglutition Disorders/radiotherapy , Esophageal Neoplasms/radiotherapy , Palliative Care/methods , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young AdultABSTRACT
BACKGROUND: The superior genetic resources of breeding pigs have been preserved for use through freezing the sperm or semen. However, because there is no way to collect their sperm or semen after depletion, the generation of sperm via the differentiation of porcine spermatogonial stem cells (SSCs) can be an alternative. To date, there have been no reports of techniques customized to in-vitro culture and differentiation into sperm in porcine SSCs. Accordingly, it is important to preserve porcine SSCs with outstanding genetic backgrounds until these technologies are developed. Unfortunately, a protocol for the long-term preservation of porcine SSCs has yet to be reported. OBJECTIVE: We tried to develop a cryopreservation medium to preserve the characteristics of undifferentiated porcine SSCs for long-term cryopreservation. MATERIALS AND METHODS: SSCs retrieved from porcine testes were freeze-cryopreserved in StemPro-34 medium supplemented with various concentrations of fetal bovine serum (FBS), dimethyl sulfoxide (DMSO), and trehalose; then, after 7 days, the viability and alkaline phosphatase (AP) activity was measured in thawed porcine SSCs. Additionally, we investigated the use of hypotaurine and/or glutathione as antioxidants in the optimized freezing medium for maintaining the viability and AP activity of porcine SSCs during the freezing-cryopreservation-thawing process. RESULTS: Porcine SSCs frozen-cryopreserved-thawed in StemPro-34 medium supplemented with 10% (v/v) FBS, 10% (v/v) DMSO, 200 mM trehalose, 5 mM hypotaurine, and 5 mM glutathione showed the highest viability and AP activity. CONCLUSION: We optimized a cryopreservation medium that inhibits the loss of viability and the increases differentiation post-thawing of the frozen porcine SSCs.
ABSTRACT
We evaluated the effect of pre-operative serratus anterior plane block on postoperative pain and opioid consumption after thoracoscopic surgery. We randomly allocated 89 participants to block with 30 ml ropivacaine 0.375% (n = 44), or no block without placebo or sham procedure (n = 45). We analysed results from 42 participants in each group. Serratus anterior plane block reduced mean (SD) remifentanil dose during surgery, 0.12 (0.06) mg.h-1 vs. 0.16 (0.06) mg.h-1 , p = 0.016, and reduced mean (SD) fentanyl consumption in the first 24 postoperative hours, 3.8 (1.9) µg.kg-1 vs. 5.7 (1.6) µg.kg-1 , p = 0.000004. Block also reduced the worst median (IQR [range]) pain scores reported in the first 24 postoperative hours: 6 (5-7 [3-10]) vs. 7 (6-7 [3-10]), p = 0.027. Block decreased dissatisfaction with pain management, categorised as 'highly unsatisfactory', 'unsatisfactory', 'neutral', 'satisfactory' or 'highly satisfactory': 1/2/21/18/0 vs. 1/14/15/11/1, p = 0.0038. There were no differences in the rates of nausea, vomiting, dizziness or length of hospital stay. Serratus anterior plane block may be used to reduce pain and opioid use after thoracoscopic lung surgery.
Subject(s)
Nerve Block/methods , Pain, Postoperative/prevention & control , Thoracoscopy/adverse effects , Adult , Aged , Aged, 80 and over , Analgesics, Opioid/administration & dosage , Drug Administration Schedule , Female , Fentanyl/administration & dosage , Humans , Male , Middle Aged , Pain Measurement/methods , Pain, Postoperative/etiology , Patient Satisfaction , Remifentanil/administration & dosage , Young AdultABSTRACT
This study examined whether the distribution of biochemical, physiological, and metabolic risk factors for non-communicable diseases (NCDs) among children and youth in urban India vary by socioeconomic status (SES). Data were derived from a cross-sectional survey of students enrolled in the 2nd and 11th grades in 19 randomly selected schools in Delhi (Nâ¯=â¯1329) in 2014-15. Mixed-effect regression models were used to determine the prevalence of risk factors for NCDs among private (higher SES) and government (lower SES) school students. After adjusting for age, gender, and grade we found the percentage of overweight (13.16% vs. 3.1%, p valueâ¯<â¯0.01) and obese (8.7% vs. 0.3%, p valueâ¯<â¯0.01) students was significantly higher among private relative to government school students. Similarly, significantly higher percentage of private school students had higher waist circumference values (7.72% vs. 0.58%, p valueâ¯<â¯0.01) than government school students. Furthermore, similar trend was observed across schools in the distribution of other NCD risk factors: raised blood pressure, raised total cholesterol, and low-density lipoprotein. Surprisingly, despite a higher prevalence of all risk factors, significantly higher percentage of private school students had adequate/ideal levels of high-density lipoprotein. Overall, the risk profile of private school students suggests they are more vulnerable to future NCDs.
ABSTRACT
Autophagy provides a mechanism for the turnover of cellular organelles and proteins through a lysosome-dependent degradation pathway and is a possible mechanism in inflammatory disease. Periodontitis is an inflammatory disease caused by periodontal pathogens. Porphyromonas gingivalis, an important periodontal pathogen, activates cellular autophagy to provide a replicative niche while suppressing apoptosis in endothelial cells. However, the molecular basis for a causal relationship between P. gingivalis and autophagy is unclear. This research examines the involvement of P. gingivalis in autophagy through light chain 3 (LC3) and autophagic proteins, and the role of P. gingivalis-induced autophagy in the clearance of P. gingivalis and inflammation. To investigate the molecular mechanism of autophagy induced by P. gingivalis, PMA-differentiated THP-1-derived macrophages were infected with live P. gingivalis. The P. gingivalis increased the formation of autophagosomes in a multiplicity of infection-dependent manner, as well as autophagolysosomes. Porphyromonas gingivalis activated LC3-I/LC3-II conversion and increased the conjugation of autophagy-related 5 (ATG5) -ATG12 and the expression of Beclin1. The expressions of Beclin1, ATG5-ATG12 conjugate, and LC3-II were significantly inhibited by the presence of 3-methyladenine, an autophagy inhibitor. Interestingly, 3-methyladenine increased the survival of P. gingivalis and proinflammatory cytokine interleukin-1ß production. The data indicate that P. gingivalis induces autophagy in PMA-differentiated THP-1-derived macrophages and in turn, macrophages eliminate P. gingivalis through an autophagic response, which can lead to the restriction of an excessive inflammatory response by downregulating interleukin-1ß production. The induction of autophagy by P. gingivalis may play an important role in the periodontal inflammatory process and serve as a target for the development of new therapies.
Subject(s)
Autophagy/physiology , Macrophages/microbiology , Porphyromonas gingivalis/pathogenicity , Animals , Autophagosomes , Autophagy/immunology , Cell Differentiation , Cytokines/immunology , Cytokines/metabolism , HEK293 Cells , Humans , Inflammation/immunology , Inflammation/microbiology , Inflammation/pathology , Lysosomes , Macrophages/pathology , Mice , Periodontitis/metabolism , Periodontitis/microbiologyABSTRACT
Accurate detection of oestrus is important for artificial insemination. The aim of this study was to identify oestrous-specific bovine cervical mucus proteins that could be used to determine the optimal time for artificial insemination. Non-oestrous and controlled internal drug release (CIDR)-induced oestrous-stage mucus proteins were purified and subjected to surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, sodium dodecyl sulphate polyacrylamide gel electrophoresis and MALDI-TOF/TOF. Among differentially expressed proteins, lactoferrin (LF) and glutamate receptor-interacting protein 1 (GRIP1) showed a twofold increase during the CIDR-induced oestrous stage compared to the levels in non-oestrous stage in bovine cervical mucus. The RT-PCR, Western blotting and immunohistochemistry results showed that LF and GRIP1 expression was significantly increased during the oestrous stage in the uterus. This study demonstrated that bovine LF and GRIP1 exist during the oestrous stage, but not during the non-oestrous stage, suggesting that cervical mucus LF and GRIP1 are useful oestrous detection markers in cattle.
Subject(s)
Cervix Mucus/physiology , Estrus/metabolism , Lactoferrin/metabolism , Receptors, Glutamate/metabolism , Animals , Biomarkers/metabolism , Cattle , Electrophoresis, Polyacrylamide Gel , Female , Lactoferrin/genetics , RNA, Messenger/genetics , Random Allocation , Receptors, Glutamate/genetics , Spectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationABSTRACT
OBJECTIVE: For deceased-donor organ transplantations, negative T cell crossmatches (XMs) are mandatory for kidney and pancreas allocation in the Korean Network for Organ Sharing (KONOS) organ allocation system. Submission and periodic renewal of serum to the KONOS is required for all transplantation candidates of kidney or pancreas and these sera are distributed to 23 laboratories for preliminary XMs. We have investigated how sensitization status varies among transplantation candidates waitlisted for different organs. METHODS: Positive rates of T cell XMs performed during recent 1-year period (from March 2014 to February 2015) in the Korea Organ Donation Agency laboratory have been analyzed according to different organs. For 163 cases of deceased donors, 3605 recipients (22.1 recipients per one donor) were crossmatched using both of National Institutes of Health and antihuman globulin complement-dependent cytotoxicity (CDC) methods and flow cytometry method. RESULTS: T cell XM positive rates varied among transplantation candidates for different organs. The positive rate was high for kidney (485/3,145, 15.4%), and low for pancreas or kidney/pancreas (7/200, 3.5%), lung (0/41, 0%), and heart (11/221, 5.0%). Among XM-positive individuals, nearly two-thirds of the kidney transplantation candidates showed strong sensitization status with CDC+/flow+ results (64.5%), whereas pancreas or kidney/pancreas transplantation candidates more commonly showed weaker sensitization status with CDC-/flow+ results (85.7%). CONCLUSION: Kidney transplantation candidates show a much higher positive rate and stronger sensitization status than candidates for other organs. The results of this study would be useful for determining the number of candidates to be crossmatched for different organs.
Subject(s)
Histocompatibility Testing , Organ Transplantation , Tissue and Organ Procurement , Waiting Lists , Female , Flow Cytometry , Histocompatibility Testing/methods , Humans , Middle Aged , Republic of Korea , T-Lymphocytes/immunology , Tissue Donors , United StatesABSTRACT
The human leucocyte antigen (HLA) system is the most polymorphic genetic system in humans, and HLA matching is crucial in organ transplantation, especially in hematopoietic stem cell transplantation. We investigated HLA-A, HLA-B and HLA-DRB1 allele and haplotype frequencies at allelic level in 10 918 Koreans from bone marrow donor registry in Korea. Intermediate resolution HLA typing was performed using Luminex technology (Wakunaga, Japan), and additional allelic level typing was performed using PCR-single-strand conformation polymorphism method and/or sequence-based typing (Abbott Molecular, USA). Allele and haplotype frequencies were calculated by direct counting and maximum likelihood methods, respectively. A total of 39 HLA-A, 66 HLA-B and 47 HLA-DRB1 alleles were identified. High-frequency alleles found at a frequency of ≥5% were 6 HLA-A (A*02:01, *02:06, *11:01, *24:02, *31:01 and *33:03), 6 HLA-B (B*15:01, *35:01, *44:03, *51:01, 54:01 and *58:01) and 8 HLA-DRB1 (DRB1*01:01, *04:05, *04:06, *07:01, *08:03, *09:01, *13:02 and *15:01) alleles. At each locus, A*02, B*15 and DRB1*14 generic groups were most diverse at allelic level, consisting of 9, 12 and 11 different alleles, respectively. A total of 366, 197 and 21 different HLA-A-B-DRB1 haplotypes were estimated with frequencies of ≥0.05%, ≥0.1% and ≥0.5%, respectively. The five most common haplotypes with frequencies of ≥2.0% were A*33:03-B*44:03-DRB1*13:02 (4.97%), A*33:03-B*58:01-DRB1*13:02, A*33:03-B*44:03-DRB1*07:01, A*24:02-B*07:02-DRB1*01:01 and A*24:02-B*52:01-DRB1*15:02. Among 34 serologic HLA-A-B-DR haplotypes with frequencies of ≥0.5%, 17 haplotypes revealed allele-level diversity and majority of the allelic variation was arising from A2, A26, B61, B62, DR4 and DR14 specificities. Haplotype diversity obtained in this study is the most comprehensive data thus far reported in Koreans, and the information will be useful for unrelated stem cell transplantation as well as for disease association studies.
Subject(s)
Bone Marrow Transplantation/methods , HLA-A Antigens/genetics , HLA-B Antigens/genetics , HLA-DRB1 Chains/genetics , Tissue Donors , Alleles , Asian People/genetics , Gene Frequency , Genotype , Haplotypes , Histocompatibility Testing , Humans , Registries , Republic of KoreaABSTRACT
Diffuse peripheral nerve impairment is common in metabolic syndrome: in patients with metabolic syndrome and carpal tunnel syndrome this might affect the outcome of treatment by local corticosteroid injection. A total of 55 consecutive patients with carpal tunnel syndrome and metabolic syndrome treated with corticosteroid injection (10 mg triamcinolone acetonide) were age and sex matched with 55 control patients without metabolic syndrome. Grip strength, perception of touch with Semmes-Weinstein monofilaments and Boston Carpal Tunnel Questionnaires were assessed at the baseline and at 6, 12 and 24 weeks follow-up. The two groups had similar pre-operative grip strength and Boston Carpal Tunnel Questionnaire scores. The Boston Carpal Tunnel Questionnaire symptom and function scores of the metabolic syndrome group were significantly greater than the control group at 12 and 24 weeks follow-up. Except for significantly greater grip strength at the 12-week follow-up in the control group, there were no significant differences in grip strength between the groups. Semmes-Weinstein monofilament sensory index for the control group was significantly greater than that of the metabolic syndrome group throughout the 24-week follow-up. After 24 weeks, five patients (13%) in the control group and 13 patients (27%) in the metabolic syndrome group had had carpal tunnel surgery. Patients with metabolic syndrome are at risk for poor functional outcome and failure of treatment after corticosteroid injection for carpal tunnel syndrome. LEVEL OF EVIDENCE: Treatment benefits III.
Subject(s)
Carpal Tunnel Syndrome/complications , Carpal Tunnel Syndrome/drug therapy , Glucocorticoids/therapeutic use , Metabolic Syndrome/complications , Triamcinolone Acetonide/therapeutic use , Adult , Case-Control Studies , Female , Hand Strength , Humans , Injections, Intra-Articular , Male , Middle Aged , Surveys and Questionnaires , Treatment OutcomeABSTRACT
Concanavalin A (Con A)-induced hepatitis model is well-established experimental T cell-mediated liver disease. Reactive oxygen species (ROS) is associated with T-cell activation and proliferation, but continued ROS exposure induces T-cell hyporesponsiveness. Because glutathione peroxidase 1 (Gpx1) is an antioxidant enzyme and is involved in T-cell development, we investigated the role of Gpx1 during Con A-induced liver injury in Gpx1 knockout (KO) mice. Male wild-type (WT) mice and Gpx1 KO mice were intravenously injected with Con A (10 mg/kg), and then killed after 8 h after Con A injection. Serum levels of aspartate transaminase and alanine transaminase were measured to assess hepatic injury. To identify that Gpx1 affects T cell-mediated inflammation, we pretreated Gpx1 inhibitor to Human Jurkat T cells then treated Con A. Con A-induced massive liver damage in WT mice but its damage was attenuated in Gpx1 KO mice. Con A-induced Th1 cytokines such as tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and interleukin (IL)-2 were also decreased in the liver and spleen of Gpx1 KO mice compared with WT mice. In Jurkat T cells, Con A-induced mRNA levels of IL-2, IFN-γ and TNF-α were downregulated by pretreatment of Gpx inhibitor, mercaptosuccinic acid. We also observed that Gpx1 KO mice showed increasing oxidative stress in the liver and spleen compared with WT mice. These results suggest that Gpx1 deficiency attenuates Con A-induced liver injury by induction of T-cell hyporesponsiveness through chronic ROS exposure.
Subject(s)
Concanavalin A/toxicity , Glutathione Peroxidase/metabolism , Lymphocyte Activation/drug effects , Alanine Transaminase/blood , Animals , Aspartate Aminotransferases/blood , Down-Regulation/drug effects , Enzyme Inhibitors/pharmacology , Glutathione Peroxidase/antagonists & inhibitors , Glutathione Peroxidase/genetics , Humans , Interferon-gamma/genetics , Interferon-gamma/metabolism , Interleukin-2/genetics , Interleukin-2/metabolism , Jurkat Cells , Liver/injuries , Liver/metabolism , Liver/pathology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Oxidative Stress/drug effects , Phosphorylation/drug effects , Reactive Oxygen Species/metabolism , Spleen/metabolism , T-Lymphocytes/cytology , T-Lymphocytes/metabolism , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , Glutathione Peroxidase GPX1ABSTRACT
Large insertions and deletions (indels), including copy number variations (CNVs), are commonly seen in many diseases. Standard approaches for indel detection rely on well-established methods such as qPCR or short tandem repeat (STR) markers. Recently, a number of tools for CNV detection based on next-generation sequencing (NGS) data have also been developed; however, use of these methods is limited. Here, we used whole-exome sequencing (WES) in patients previously diagnosed with CMT1A or HNPP using STR markers to evaluate the ability of WES to improve the clinical diagnosis. Patients were evaluated utilizing three CNV detection tools including CONIFER, ExomeCNV and CEQer, and array comparative genomic hybridization (aCGH). We identified a breakpoint region at 17p11.2-p12 in patients with CMT1A and HNPP. CNV detection levels were similar in both 6 Gb (mean read depth = 80×) and 17 Gb (mean read depth = 190×) data. Taken together, these data suggest that 6 Gb WES data are sufficient to reveal the genetic causes of various diseases and can be used to estimate single mutations, indels, and CNVs simultaneously. Furthermore, our data strongly indicate that CNV detection by NGS is a rapid and cost-effective method for clinical diagnosis of genetically heterogeneous disorders such as CMT neuropathy.
Subject(s)
Arthrogryposis/genetics , Charcot-Marie-Tooth Disease/genetics , Chromosomes, Human, Pair 17/chemistry , DNA Copy Number Variations , Exome , Hereditary Sensory and Motor Neuropathy/genetics , INDEL Mutation , Arthrogryposis/diagnosis , Arthrogryposis/pathology , Charcot-Marie-Tooth Disease/diagnosis , Charcot-Marie-Tooth Disease/pathology , Chromosome Breakpoints , Comparative Genomic Hybridization , Genome-Wide Association Study , Hereditary Sensory and Motor Neuropathy/diagnosis , Hereditary Sensory and Motor Neuropathy/pathology , High-Throughput Nucleotide Sequencing , Humans , Microsatellite Repeats , SoftwareABSTRACT
PURPOSE: Pregnancy is a known predisposing factor for central serous chorioretinopathy (CSC). Choroidal thickness (CT) increases in patients with CSC. This study was designed to evaluate CT in pregnant women.Patients and methodsThis was a prospective study. Fourteen healthy pregnant women and seven patients with pre-eclampsia were included. Twenty-one normal subjects were also recruited. CT was measured using enhanced-depth imaging optical coherence tomography. RESULTS: The mean CT of normal subjects, healthy pregnant women and patients with pre-eclampsia were 264.95±21.03, 274.23±29.30 and 389.79±25.13 µm, respectively (normal subjects vs healthy gravidas: P>0.05; normal subjects vs pre-eclampsia: P<0.001; healthy gravidas vs pre-eclampsia: P<0.001). CT decreased from 381.05±22.96 µm to 335.17±9.97 µm 1 week after delivery in patients with pre-eclampsia. CONCLUSIONS: Pregnancy itself did not increase CT, whereas pre-eclampsia did appear to result in increased CT. This suggests that additional unknown factors induce hyperpermeability in pregnant women.
Subject(s)
Choroid/anatomy & histology , Choroid/pathology , Pre-Eclampsia/etiology , Adult , Female , Fovea Centralis , Gestational Age , Healthy Volunteers , Humans , Organ Size , Pre-Eclampsia/physiopathology , Pregnancy , Prospective Studies , Tomography, Optical CoherenceABSTRACT
We report microporous carbon nanosheets containing numerous redox active heteroatoms fabricated from exfoliated waste coffee grounds by simple heating with KOH for pseudocapacitive charge storage. We found that various heteroatom combinations in carbonaceous materials can be a redox host for lithium ion storage. The bio-inspired nanomaterials had unique characteristics, showing superior electrochemical performances as cathode for asymmetric pseudocapacitors.
ABSTRACT
INTRODUCTION: Angiotensin II is a peptide hormone involved in the renin-angiotensin system (RAS). Anti-angiotensin receptor 1 (AT1R) antibodies are implicated in stimulating RAS and are suspected to have some adverse impacts on renal transplantation outcome. METHODS: From November 2009 to February 2012, 37 remaining sera from renal transplantation recipients with biopsy-proven antibody-mediated rejection (AMR) (n = 6), acute cellular rejection (ACR) (n = 23), and AMR + ACR (n = 8) without preformed human leukocyte antigeon (HLA) antibodies were tested with anti-AT1R antibody assay. Forty-two control patients without rejection also were analyzed. RESULTS: The frequency of elevated anti-AT1R antibodies was higher in patients with AMR (n = 14) compared to controls (28.6% vs 4.9%, P = .03, OR = 8.0). It was also higher in patients with AMR + ACR (n=8) (37.5% vs 4.9%, P = .03, OR = 12.0). There was no difference in frequencies of elevated anti-AT1R antibody in patients with ACR. CONCLUSION: Anti-AT1R antibodies were suspected to be associated with occurrence of AMR without preformed HLA antibodies in renal transplantation. Further studies in a larger number of patients are needed.
Subject(s)
Graft Rejection/immunology , HLA Antigens/immunology , Kidney Transplantation , Receptor, Angiotensin, Type 1/immunology , Adolescent , Adult , Antibodies/immunology , Female , Humans , Kidney Transplantation/adverse effects , Male , Middle Aged , Renin-Angiotensin System , Tissue Donors , Young AdultABSTRACT
PURPOSE: To evaluate the effectiveness of the ICare rebound tonometer in patients with overestimated intraocular pressure (IOP) due to tight orbit syndrome and to identify factors affecting the development of tight orbit syndrome in glaucoma patients. METHODS: We investigated 84 eyes in 84 glaucoma patients, of which 14 eyes were classified in the tight orbit syndrome group and 70 eyes in the control group. IOP was measured using the ICare tonometer and the Goldmann applanation tonometer (GAT). The demographic data, medical histories, ocular histories, and detailed ocular drug histories of the two groups were compared to identify factors contributing to the development of tight orbit syndrome. RESULTS: In the tight orbit syndrome group, the ICare tonometer significantly underestimated the IOP by approximately 8.6 mmHg compared with the GAT. In the control group, the IOP readings of the GAT and the ICare tonometer did not differ significantly. Bland-Altman analysis showed that the mean difference between measurements taken using the GAT and those taken using the ICare tonometer was 2.5 ± 6.3 mmHg. The difference between the GAT and ICare tonometer measurements was greater in the tight orbit syndrome group (8.6 ± 5.3 mmHg) than in the control group (1.3 ± 2.7 mmHg). Multivariate regression analysis revealed that only the use of prostaglandin analogs (PGAs) was associated with the development of tight orbit syndrome. CONCLUSIONS: The ICare tonometer is a suitable alternative device for use in patients with tight orbit syndrome in whom the IOP may be overestimated with the GAT. The prolonged use of PGAs is significantly associated with the development of tight orbit syndrome.
Subject(s)
Glaucoma/diagnosis , Intraocular Pressure/physiology , Orbital Diseases/complications , Tonometry, Ocular/instrumentation , Aged , Aged, 80 and over , Antihypertensive Agents/therapeutic use , Case-Control Studies , Eyelid Diseases/complications , Female , Glaucoma/drug therapy , Glaucoma/etiology , Humans , Male , Middle Aged , Reproducibility of ResultsABSTRACT
Recently, isolation and in vitro culture of putative spermatogonial stem cells (SSCs) in the domestic cat have been conducted. However, the cellular niche conditions that facilitate the establishment and long-term maintenance of feline SSCs (FSSCs) have not been described. Therefore, we investigated the type of feeder cells used to stimulate colony formation and growth of FSSCs among the various factors in the FSSC niche. Spermatogonial stem cells isolated from feline testes were cultured on mitotically inactivated testicular stromal cells (TSCs) derived from cats, dogs and mice, and mouse embryonic fibroblasts (MEFs). The formation and growth of colonies derived from SSCs cultured on each type of feeder cell were identified at passage 0, and the morphology, alkaline phosphatase (AP) activity and expression of SSC-specific genes in surviving colonies were investigated at passage 4. Among these diverse feeder cells, TSCs from cat showed the greatest colony formation, growth and maintenance of FSSCs, and SSC colonies cultured by passage 4 showed a typical dome-shaped morphology, AP activity and expression of SSC-specific genes (NANOG, OCT4, SOX2 and CD9). Accordingly, these results demonstrate that feline TSCs could be used as feeder cells to support the establishment and maintenance of SSCs from domestic cats.