Triple-negative breast cancer (TNBC) harbors genetic heterogeneity and generally has more aggressive clinical outcomes. As such, there is urgency in identifying new prognostic targets and developing novel therapeutic strategies. In this study, miR-224 was overexpressed in breast cancer cell lines and TNBC primary cancer samples. Knockdown of miR-224 in MDA-MB-231 cancer cells reduced cell proliferation, migration, and invasion. Through integrating in silico prediction algorithms with KEGG pathway and Gene Ontology analyses, CASP9 was identified to be a potential target of miR-224. miR-224 knockdown significantly increased CASP9 transcript and protein levels. Furthermore, luciferase reporter assays confirmed a direct interaction of miR-224 with CASP9. Our findings have demonstrated that the miR-224/CASP9 axis plays an important role in TNBC progression, providing evidence in support of a promising therapeutic strategy for this disease.
http://bit.ly/2E6ePwf
Κυριακή 10 Φεβρουαρίου 2019
MicroRNA-224 Promotes Tumorigenesis through Downregulation of Caspase-9 in Triple-Negative Breast Cancer
A Genetic Variant in GPR126 Causing a Decreased Inclusion of Exon 6 Is Associated with Cartilage Development in Adolescent Idiopathic Scoliosis Population
Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity disease in adolescents but its etiology and pathogenesis are still unclear. The current study aims to identify the relationship between single nucleotide polymorphisms (SNPs) of G protein-coupled receptor 126 (GPR126) gene and AIS predisposition. GPR126 contains 26 exons and alternative splicing of exon 6 and exon 25 produces 4 protein-coding transcripts. We genotyped SNPs of GPR126 gene around exon 6 and exon 25 in 131 Chinese AIS patients and 132 healthy controls and provided evidence that SNP rs41289839 G>A is strongly associated with AIS susceptibility. Linkage disequilibrium analysis suggests that rs41289839 and other AIS-related SNPs were in strong LD. Next, we demonstrated that rs41289839 G>A inhibits the inclusion of exon 6 during alternative splicing, resulting in a decreased expression level of exon 6-included transcript (GPR126-) relative to the exon 6 excluded transcript (GPR126-) by minigene assay. Chondrogenic differentiation experiment showed that GPR126- has a high expression level relative to GPR126- during chondrogenic differentiation of hMSCs. Our findings indicate that newly discovered SNP is related to cartilage development and may provide valuable insights into the etiology and pathogenesis of adolescent idiopathic scoliosis.
http://bit.ly/2TD6BB7
Milking of the Umbilical Cord in Term and Late Preterm Infants
Introduction. Umbilical cord milking is a procedure in which clamped or unclamped umbilical cord is grasped, and blood is pushed ("stripped") two to four times towards the newborn, in a rapid time frame, usually within 20 seconds. The target of umbilical cord milking is to provide infants with their whole potential blood volume—of which they are deprived when early cord clamping is carried out—completing placental transfusion in a shorter time than delayed cord clamping. The aim of this narrative review is to analyse the literature regarding umbilical cord milking in term and late-preterm infants and to assess all possible benefits and limits of this procedure in clinical practice, especially in comparison to immediate and delayed cord clamping. Methods. We analysed literature data concerning maternal, as well as neonatal, outcomes for term and late-preterm (gestational age ≥ 34 weeks) newborns who received umbilical cord milking. Results. Most studies show comparable benefits for both umbilical cord milking and delayed cord clamping, especially in terms of haematological parameters when compared to immediate cord clamping. Umbilical cord milking may be a feasible procedure also for newborns requiring resuscitation. Conclusions. Literature data concerning positive effects of umbilical cord milking are encouraging and suggest that umbilical cord milking may be a quick and effective method to provide placental transfusions to depressed infants. However, the lack of standardised procedures and the variation in evaluated outcomes as well as the limited number of patients enrolled in trials, along with the retrospective nature of some of them, prevent recommending umbilical cord milking as a routine procedure.
http://bit.ly/2BvjsOV
Learning Curve for Using Intraoperative Neural Monitoring Technology of Thyroid Cancer
We investigated the learning curve for using intraoperative neural monitoring technology in thyroid cancer, with a view to reducing recurrent laryngeal nerve injury complications. Radical or combined radical surgery for thyroid cancer was performed in 82 patients with thyroid cancer and 147 recurrent laryngeal nerves were dissected. Intraoperative neural monitoring technology was applied and the "four-step method" used to monitor recurrent laryngeal nerve function. When the intraoperative signal was attenuated by more than 50%, recurrent laryngeal nerve injury was diagnosed, and the point and causes of injury were determined. The time required to identify the recurrent laryngeal nerve was 0.5–2 min and the injury rate was 2.7%; injuries were diagnosed intraoperatively. Injury most commonly occurred at or close to the point of entry of the nerve into the larynx and was caused by stretching, tumor adhesion, heat, and clamping. The groups are divided in chronological order; a learning curve for using intraoperative neural monitoring technology in thyroid cancer surgery was generated based on the time to identify the recurrent laryngeal nerve and the number of cases with nerve injury. The time to identify the recurrent laryngeal nerve and the number of injury cases decreased markedly with increasing patient numbers. There is a clear learning curve in applying intraoperative neural monitoring technology to thyroid cancer surgery; appropriate use of such technology aids in the protection of the recurrent laryngeal nerve.
http://bit.ly/2TOeF2d
Innovating Cancer Care Delivery: the Example of the 4R Oncology Model for Colorectal Cancer Patients
Opinion statement
Care delivery innovation is necessary to address the growing complexity of cancer care across specialties and integrate new diagnostics, treatments, and services into care delivery. Informed by Cancer Care Delivery Research (CCDR), multilevel intervention research, and other disciplines, this article describes the 4-step cancer care delivery innovation cycle. The cycle guides collaborative efforts of cancer clinicians, researchers, patients, and other stakeholders to systematically define care delivery problems and formulate, test, and implement care innovations to effectively address problems. We illustrate the 4 steps of the innovation cycle with the example of developing the 4R Oncology Model for colorectal cancer (4R is Right Information and Right Care for the Right Patient at the Right Time). The 4R is a multilevel intervention informed by CCDR, the team science, and lessons learned from other models, such as survivorship care planning. We offer additional considerations for balancing the need to innovate with concerns about constrained resources and overextended workforce. We suggest to focus on care delivery models which are synergistic with other efforts and do not require extensive information systems support in earlier cycles of development.
http://bit.ly/2E3xn0d
Treatment Approaches for Cisplatin-Ineligible Patients with Invasive Bladder Cancer
Opinion statement
Cisplatin has been established as an important agent in the neoadjuvant setting prior to radical cystectomy (RC) surgery for muscle-invasive urothelial cancer (MIUC) as well as in the unresectable or metastatic urothelial carcinoma (mUC) setting. Unfortunately, many patients in practice are felt to be "cisplatin-ineligible." Thus, it is vital that we develop treatment approaches and novel therapeutics for this population. We evaluate therapeutic alternatives to cisplatin-based treatment. For patients undergoing RC, there is no recommended alternative to neoadjuvant cisplatin-based combination therapy, and upfront RC or clinical trials are preferable. For patients receiving "bladder-sparing" radiation, concurrent radiosensitizing chemotherapies may be used, and several trials are also underway. For cisplatin-ineligible patients with mUC who are eligible for chemotherapy, carboplatin-based or split-dose cisplatin-based regimens may be employed. Pembrolizumab and atezolizumab offer options as first-line therapy for cisplatin-ineligible patients with high PD-L1 expression. The results of trials combining checkpoint inhibitors or platinum-based chemotherapy plus PD1/PD-L1 inhibitors are eagerly awaited. For platinum or chemotherapy-ineligible patients with mUC, immune checkpoint inhibitors such as inhibitors of programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) are approved regardless of PD-L1 expression. However, given limited effectiveness of first-line PD-1/PD-L1 inhibitor monotherapy in tumors with low PD-L1 expression, trials in this space are critical.
http://bit.ly/2GB3upN
Vitamin A deficiency execrates Lewis lung carcinoma via induction of type 2 innate lymphoid cells and alternatively activates macrophages
Vitamin A deficiency diet fed tumor‐bearing mice have lower survival rate, larger tumor size compared to normal diet fed mice.
Abstract
Background
Lung carcinoma is still associated with high rates of morbidity and mortality despite the advances in cancer therapy achieved in last decades. Recent studies showed that immune responses played a crucial role in the developments of cancers including lung cancer. Type 1 immune response could promote classical activated macrophages (CAMs) with antitumor properties. On the contrast, type 2 immune response could lead to the polarization of alternatively activated macrophages (AAMs) which could promote the growth and metastasis of tumor. Our previous research showed that vitamin A deficiency could promote the type 2 immune response but not the type 1 immune response. Whether vitamin A deficiency has detrimental effect for lung carcinoma need further investigate.
Aim
To investigate the effect of vitamin A deficiency in lung cancer and the potential mechanisms.
Methods
Mice were fed with normal diet or vitamin A deficiency diet for 2 weeks, and then, Lewis lung cancer (LLC) cells dissolved in Matrigel Matrix were planted on the left lower lope of lungs. Mice were sacrificed 28 days after the plantation of tumor cells, the tumor size, cytokine profile in bronchoalveolar lavage fluid (BALF), numbers of type 2 innate lymphoid cells (ILC2s), and macrophage phenotypes in the lung were measured. The overall survival rate was also monitored throughout the experiments.
Results
Vitamin A deficiency diet fed tumor‐bearing mice have lower survival rate (χ 2 = 6.862, p < 0.001), larger tumor size (t = 2.651, p < 0.05), more ILC2s (t = 7.680, p < 0.001), and AAMs (t = 6.315, p < 0.001) in the lung tissue; also, type 2 cytokines concentrations in the BALF were higher compared to normal diet fed ones.
Conclusion
Vitamin A deficiency could promote the pathogeneses of lung carcinoma via induction of ILC2s and polarizing AAMs.
http://bit.ly/2US355U
Exploring a potential mechanistic role of DNA methylation in the relationship between in utero and post‐natal environmental exposures and risk of childhood acute lymphoblastic leukaemia
The aetiology of childhood acute lymphoblastic leukaemia (ALL) is unclear. Genetic abnormalities have been identified in a number of ALL cases, although these alone are not sufficient for leukaemic transformation. Various in utero and post‐natal environmental exposures have been suggested to alter risk of childhood ALL. DNA methylation patterns can be influenced by environmental exposures, and are reported to be altered in ALL, suggesting a potential mediating mechanism between environment and ALL disease risk. To investigate this, we used a 'meet in the middle' approach, investigating the overlap between exposure‐associated and disease‐associated methylation change. Genome‐wide DNA methylation changes in response to possible ALL‐risk exposures (i.e. breast feeding, infection history, day care attendance, maternal smoking, alcohol, caffeine, folic acid, iron, and radiation exposure) were investigated in a sub‐population of the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort using an epigenome‐wide association study (EWAS) approach (n=861‐927), and compared to a list of ALL disease‐associated methylation changes compiled from published data. Hypergeometric probability tests suggested that the number of directionally concordant gene methylation changes observed in ALL disease and in response to the following exposures; maternal radiation exposure (p=0.001), alcohol intake (p=0.006); sugary caffeinated drink intake during pregnancy (p=0.045); and infant day care attendance (p=0.003), were not due to chance. Data presented suggests that DNA methylation may be one mediating mechanism in the multiple hit pathway needed for ALL disease manifestation.
This article is protected by copyright. All rights reserved.
http://bit.ly/2GhVLh3
The association of female sex with application of evidence-based practice recommendations for perioperative care in hip fracture surgery [Research]
BACKGROUND:
Sex and gender inequality is prevalent in health care, and affects receipt of health care services and outcomes. Our objective was to measure the association between sex and receipt of evidence-based perioperative care for hip fracture in Ontario.
METHODS:This was a population-based retrospective cross-sectional analysis. We identified all Ontario residents aged 66 years and older who had hip fracture surgery between 2014 and 2016. After protocol registration, we measured the adjusted association between female sex and perioperative geriatric care (primary outcome), anesthesia consultations, regional analgesia and neuraxial anesthesia (secondary outcomes) using multilevel multivariable adjusted logistic regression. Pre-specified sensitivity analyses were also performed.
RESULTS:We identified 22 661 patients who had hip fracture surgery; 16 162 (71.3%) were women. Women were less likely to receive perioperative geriatric care (adjusted odds ratio [OR] 0.80, 95% confidence interval [CI] 0.72 to 0.88) and anesthesia consultations (adjusted OR 0.89, 95% CI 0.80 to 0.98); women were more likely to have timely surgery (adjusted OR 1.26, 95% CI 1.17 to 1.36). Receipt of neuraxial anesthesia (adjusted OR 0.98, 95% CI 0.93 to 1.04) and regional analgesia (adjusted OR 1.00, 95% CI 0.94 to 1.07) were not different between sexes.
INTERPRETATION:More than 2 out of 3 patients who had hip fracture surgery were women; however, women were less likely to receive perioperative geriatric care and anesthesia consultations. Given the effectiveness of these interventions for improving outcomes, population-level hip fracture outcomes may be improved by decreasing sex-based disparities in application of evidence-based recommended perioperative care. Protocol registration: ClinicalTrials.gov, no. NCT03422497
http://bit.ly/2Sqk1nl
Randomised clinical trial: gabapentin vs baclofen in the treatment of suspected refractory gastro‐oesophageal reflux‐induced chronic cough
Summary
Background
Neuromodulators are considered potential therapeutic options for refractory gastro‐oesophageal reflux‐induced chronic cough.
Aim
To compare the efficacy of gabapentin and baclofen in patients with suspected refractory gastro‐oesophageal reflux‐induced chronic cough.
Methods
Two hundred and thirty‐four patients with suspected refractory gastro‐oesophageal reflux‐induced chronic cough, who failed an 8‐week course of omeprazole and domperidone, were recruited into the open‐labelled study and randomly assigned to receive either gabapentin (maximum daily dose of 900 mg) or baclofen (maximum daily dose of 60 mg) for 8 weeks as add‐on therapy to the previous treatment. The primary end point was the successful rate of cough resolution; and the secondary end‐points included cough sensitivity to capsaicin and gastro‐oesophageal reflux disease questionnaire score and reported side effects.
Results
One hundred and eleven patients in the gabapentin group and 106 in the baclofen group completed the study. The overall success rate for cough resolution was comparable (57.3% vs 53.0%, χ 2 = 0.357, P = 0.550) between the two groups. In parallel, cough sensitivity to capsaicin and gastro‐oesophageal reflux disease questionnaire score decreased after treatment with either gabapentin or baclofen. However, gabapentin was associated with less frequent somnolence (20.5% vs 35.0%, χ 2 = 6.156, P = 0.013) and dizziness (11.1% vs 23.9%, χ 2 = 6.654, P = 0.010) than baclofen.
Conclusions
Gabapentin and baclofen have similar therapeutic efficacy for suspected refractory gastro‐oesophageal reflux‐induced chronic cough. However, gabapentin may be preferable because of fewer side effects. Trial Register: http://www.chictr.org/; No.: ChiCTR‐ONC‐13003066.
http://bit.ly/2DxnYfI
Congenital clubfoot in Europe: A population‐based study
We aimed to assess prevalence, birth outcome, associated anomalies and prenatal diagnosis of congenital clubfoot in Europe using data from the EUROCAT network, and to validate the recording of congenital clubfoot as a major congenital anomaly by EUROCAT registries. Cases of congenital clubfoot were included from 18 EUROCAT registries covering more than 4.8 million births in 1995–2011. Cases without chromosomal anomalies born during 2005–2009, were randomly selected for validation using a questionnaire on diagnostic details and treatment. There was 5,458 congenital clubfoot cases of which 5,056 (93%) were liveborn infants. Total prevalence of congenital clubfoot was 1.13 per 1,000 births (95% CI 1.10–1.16). Prevalence of congenital clubfoot without chromosomal anomaly was 1.08 per 1,000 births (95% CI 1.05–1.11) and prevalence of isolated congenital clubfoot was 0.92 per 1,000 births (95% CI 0.90–0.95), both with decreasing trends over time and large variations in prevalence by registry. The majority of cases were isolated congenital clubfoot (82%) and 11% had associated major congenital anomalies. Prenatal detection rate of isolated congenital clubfoot was 22% and increased over time. Among 301 validated congenital clubfoot cases, diagnosis was confirmed for 286 (95%). In conclusion, this large population‐based study found a decreasing trend of congenital clubfoot in Europe after 1999–2002, an increasing prenatal detection rate, and a high standard of coding of congenital clubfoot in EUROCAT.
http://bit.ly/2SHX5iO
The average relative dose intensity of R‐CHOP is an independent factor determining favorable overall survival in diffuse large B‐cell lymphoma patients
ARDI >90% can determine overall survival better than IPI. Favorable ARDI seems to be dependent on efficient neutropenia prophylaxis and cardiac protection
Abstract
The prognosis of diffuse large B‐cell lymphoma (DLBCL) patients depends on lymphoma‐ and patient‐related risk factors and is best estimated by the international prognostic index (IPI). The aim of the study was to determine whether the average relative dose intensity (ARDI) of an anthracycline‐containing regimen could predict DLBCL outcome independently from the IPI. We analyzed 223 white Caucasian DLBCL patients who completed at least four cycles of first‐line immunochemotherapy with rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisone (R‐CHOP). The ARDI was calculated by specially developed software in each individual patient, simultaneously with the chemotherapy prescription, which instantly revealed all causes of its decrease. The relevance of the ARDI for progression‐free/overall survival (PFS/OS) was evaluated. Prolonged intervals between cycles of immunochemotherapy—the most common cause of decreased ARDI (49.3%, 110/223)—were due to neutropenia (absolute neutrophil count <1.0 × 109/L) and infections. Reductions in cytostatic doses were observed in 19.7% (44/223) of patients, mainly as the consequence of cardiotoxicity (23/223, 10.3%). The OS varied significantly when the ARDI was >90% (P < 0.00001). Multivariate analysis confirmed that an ARDI>90% was an IPI‐independent predictor of prolonged PFS (HR = 0.31; 95%CI: 0.20‐0.47; P < 0.00001) and OS (HR = 0.32; 95%CI: 0.21‐0.48; P < 0.00001). With an analytic tool allowing real‐time ARDI assessment, it was possible to maintain an ARDI above 90% in 161 of 223 patients (72%). DLBCL patients with an ARDI >90% have significantly better outcome regardless of the IPI; therefore, our official recommendation is an adequate dose density through efficient neutropenia prophylaxis and cardiac protection.
http://bit.ly/2MXv9lX
RSA reactivity in response to viewing bullying film and adolescent social adjustment
Abstract
This study assessed adolescent respiratory sinus arrhythmia (RSA) reactivity while watching a bullying film clip from Boyz'n the Hood. We emphasized the importance of considering measurement context of RSA and examined whether RSA reactivity moderated the links between environmental factors (i.e., neighborhood violence, parental psychological control, and parental acceptance) and adolescent social adjustment. Data were collected from 57 adolescents and their primary caregivers. Electrocardiogram (ECG) and respiration data were obtained from adolescents. Results indicated that neighborhood violence was positively associated with aggressive behavior but only among adolescents showing RSA augmentation, not suppression. Among youth displaying RSA suppression, parental acceptance was positively linked to prosocial behavior. We propose that, in the specific context of watching a bullying film clip, RSA suppression may relate to physiological regulation of emotion, which may differentially influence adolescents' responses to socialization.
http://bit.ly/2Dv95e9
Innovations in biological assessments of chronic stress through hair and nail cortisol: Conceptual, developmental, and methodological issues
Abstract
Much of the existing research on biological mechanisms underlying the stress experience has focused largely on moment‐to‐moment stress, rather than on chronic stress, an arguably more powerful predictor of long‐term outcomes. Recent methodological innovations have paved the way for new lines of research on chronic stress, with promising implications for developmental researchers and for those who study health and adversity. In particular, there are increasing studies that have focused on chronic stress assessments by relying on cortisol derived from hair and nails as a biomarker for chronic stress. In this paper, we provide an overview of their use, describe how hair and nail cortisol ought to be conceptualized differently across the lifespan, how developmental factors may impact its interpretation, and the circumstances under which its use may be more methodologically sensible. The purpose of this review is to provoke further discussion and encourage careful research designs that utilize hair and nail cortisol for understanding the effects of chronic stress exposure from the early developmental period, across adverse contexts, and in association with psychological and physical health outcomes.
http://bit.ly/2SqbQaD
Molecular heterogeneity and early metastatic clone selection in testicular germ cell cancer development
Molecular heterogeneity and early metastatic clone selection in testicular germ cell cancer development
Molecular heterogeneity and early metastatic clone selection in testicular germ cell cancer development, Published online: 11 February 2019; doi:10.1038/s41416-019-0381-1
Molecular heterogeneity and early metastatic clone selection in testicular germ cell cancer development
https://go.nature.com/2TJauEy
Tumour cell blebbing and extracellular vesicle shedding: key role of matrikines and ribosomal protein SA
Tumour cell blebbing and extracellular vesicle shedding: key role of matrikines and ribosomal protein SA
Tumour cell blebbing and extracellular vesicle shedding: key role of matrikines and ribosomal protein SA, Published online: 11 February 2019; doi:10.1038/s41416-019-0382-0
Tumour cell blebbing and extracellular vesicle shedding: key role of matrikines and ribosomal protein SA
https://go.nature.com/2BybaWl
Inhibition of SIRT1 deacetylase and p53 activation uncouples the anti-inflammatory and chemopreventive actions of NSAIDs
Inhibition of SIRT1 deacetylase and p53 activation uncouples the anti-inflammatory and chemopreventive actions of NSAIDs
Inhibition of SIRT1 deacetylase and p53 activation uncouples the anti-inflammatory and chemopreventive actions of NSAIDs, Published online: 11 February 2019; doi:10.1038/s41416-018-0372-7
Inhibition of SIRT1 deacetylase and p53 activation uncouples the anti-inflammatory and chemopreventive actions of NSAIDs
https://go.nature.com/2TJaoNc
MST1/Hippo promoter gene methylation predicts poor survival in patients with malignant pleural mesothelioma in the IFCT-GFPC-0701 MAPS Phase 3 trial
MST1/Hippo promoter gene methylation predicts poor survival in patients with malignant pleural mesothelioma in the IFCT-GFPC-0701 MAPS Phase 3 trial
MST1/Hippo promoter gene methylation predicts poor survival in patients with malignant pleural mesothelioma in the IFCT-GFPC-0701 MAPS Phase 3 trial, Published online: 11 February 2019; doi:10.1038/s41416-019-0379-8
MST1/Hippo promoter gene methylation predicts poor survival in patients with malignant pleural mesothelioma in the IFCT-GFPC-0701 MAPS Phase 3 trial
https://go.nature.com/2Bv3yEd
White Ginseng Ameliorates Depressive Behavior and Increases Hippocampal 5-HT Level in the Stressed Ovariectomized Rats
Postmenopausal depression is closely associated with depletion of estrogen which modulates transmission of 5-HT, a key neurotransmitter that regulates stress-managing circuits in the brain. In this study, antidepressive efficacy of white ginseng (Panax gingseng Meyer, WG) was evaluated in stressed ovariectomized rats. Female Sprague Dawley rats were ovariectomized and repeatedly restraint stressed for 2 weeks (2h/day). Thirty minutes before restraint stress, rats were administered saline (control), WG 200 mg/kg (p.o.), WG 400 mg/kg (p.o.), or fluoxetine (PC, 10 mg/kg, i.p.). Tail suspension test (TST) and forced swimming test (FST) were performed to assess antidepressant effect of WG. After behavioral tests, levels of serum corticosterone (CORT) and hippocampal 5-HT were measured. Significant decrease of immobility time in TST and FST was shown in rats administered with PC or WG 400 compared to the control. WG200-treated rats showed remarkable reduction in immobility time of TST. PC, WG 200, or WG 400-administred group exhibited significant reduction of CORT compared to the control. PC or WG-treated rats exhibited remarkable increase in hippocampal 5-HT concentration compared to the control. Hippocampal 5-HT levels in WG groups were higher than those in the PC group. The present study demonstrated that WG had antidepressant efficacy in an animal model of menopausal depression. Treatment with WG enhanced hippocampal 5-HT level while suppressing depressive symptom and serum CORT level. These results provide evidence that WG plays an important role in activating serotonergic neurons in stressful situation, suggesting that WG might be a reliable natural alternative of antidepressant drugs to treat menopausal depression.
http://bit.ly/2Glgyjt
Extracellular Signal-Regulated Kinase Mediates Ebastine-Induced Human Follicle Dermal Papilla Cell Proliferation
Ebastine is a second-generation histamine H1 receptor antagonist that is used to attenuate allergic inflammation. Ebastine has also shown to affect hair loss; however, the immunoregulatory effect of ebastine cannot completely exclude the possibility of spontaneous hair regrowth in ebastine-treated mice. In this study, we examined the effects of ebastine on the growth of human follicle dermal papilla cells (HFDPC) using a WST-1 cell proliferation assay and a bromodeoxyuridine incorporation assay. Ebastine was shown to significantly increase the proliferation of HFDPC. The expression levels of cell-cycle regulatory proteins and an antiapoptotic protein were increased in ebastine-treated HFDPC. Furthermore, elevated expression levels of phospho-AKT and phospho-p44/42 extracellular signal-regulated kinase (ERK) were observed in ebastine-treated HFDPC. Ebastine-mediated HFDPC growth was completely reversed by blocking ERK kinase. The results from our present study suggest that the regulation of HFDPC proliferation by ebastine might be directly involved in hair regrowth through the ERK signaling pathway.
http://bit.ly/2GlpFkt
Identification of Candidate Genes and MicroRNAs for Acute Myocardial Infarction by Weighted Gene Coexpression Network Analysis
Background. Identification of potential molecular targets of acute myocardial infarction is crucial to our comprehensive understanding of the disease mechanism. However, studies of gene coexpression analysis via jointing multiple microarray data of acute myocardial infarction still remain restricted. Methods. Microarray data of acute myocardial infarction (GSE48060, GSE66360, GSE97320, and GSE19339) were downloaded from Gene Expression Omnibus database. Three data sets without heterogeneity (GSE48060, GSE66360, and GSE97320) were subjected to differential expression analysis using MetaDE package. Differentially expressed genes having upper 25% variation across samples were imported in weighted gene coexpression network analysis. Functional and pathway enrichment analyses were conducted for genes in the most significant module using DAVID. The predicted microRNAs to regulate target genes in the most significant module were identified using TargetScan. Moreover, subpathway analyses using iSubpathwayMiner package and GenCLiP 2.0 were performed on hub genes with high connective weight in the most significant module. Results. A total of 1027 differentially expressed genes and 33 specific modules were screened out between acute myocardial infarction patients and control samples. Ficolin (collagen/fibrinogen domain containing) 1 (FCN1), CD14 molecule (CD14), S100 calcium binding protein A9 (S100A9), and mitochondrial aldehyde dehydrogenase 2 (ALDH2) were identified as critical target molecules; hsa-let-7d, hsa-let-7b, hsa-miR-124-3, and hsa-miR-9-1 were identified as potential regulators of the expression of the key genes in the two biggest modules. Conclusions. FCN1, CD14, S100A9, ALDH2, hsa-let-7d, hsa-let-7b, hsa-miR-124-3, and hsa-miR-9-1 were identified as potential candidate regulators in acute myocardial infarction. These findings might provide new comprehension into the underlying molecular mechanism of disease.
http://bit.ly/2I5wmZF
The Effectiveness of Sterile Wound Drapes in the Prevention of Surgical Site Infection in Thoracic Surgery
Background. The rate of surgical site infections (SSIs) has decreased in parallel to advances in sterilization techniques. Such infections increase morbidity and hospitalization costs. The use of iodine-impregnated sterile wound drapes (SWDs) is recommended to prevent or reduce the incidence of these infections. However, there is a paucity of data regarding their use in thoracic surgical procedures. The aim of the present study was to evaluate the effectiveness of sterile wound drapes in the prevention of these infections and the effects on hospitalization costs. Methods. Perioperative iodine-impregnated SWDs have been used since January 2015 in the Thoracic Surgery Clinic of our hospital. A retrospective evaluation was made of patients who underwent anatomic pulmonary resection via thoracotomy with SWD in the period January 2015–2017, compared with a control group who underwent the same surgery without SWD in the 2-year period before January 2015. Factors that may have increased the risk of surgical site infection were documented and the occurrence of SSI was recorded from postoperative follow-up data. The cost analysis was performed as an important criterion to investigate the benefits of SWD. Results. Evaluation was made of 654 patients in the study group (n:380) using SWD, the operation time was significantly longer, and perioperative blood transfusion was significantly higher, whereas treatment costs (p=0.0001) and wound culture positivity (p=0.004) were significantly lower and less surgical wound debridement was performed (p=0.002). Conclusion. The findings suggest that the use of sterile wound draping in thoracic surgery procedures reduces surgical site infections and hospitalization costs.
http://bit.ly/2I4YYSO
Usnea Acid as Multidrug Resistance (MDR) Reversing Agent against Human Chronic Myelogenous Leukemia K562/ADR Cells via an ROS Dependent Apoptosis
Purpose. Multidrug resistance (MDR) is a major obstacle in chemotherapy of leukemia treatments. In this paper, we investigated Usnea Acid (UA) as MDR reversal agent on hematologic K562/ADR cells via ROS dependent apoptosis. Methods. CCK8 assay was used to measure cell viability rate of K562/ADR. Intracellular reactive oxygen species (ROS) generation, cell cycle distribution, cell apoptosis were measured with flow cytometry, respectively. Proteins related to apoptosis were measured by Western blot. Intracellular Adriamycin accumulation was observed by confocal microscopy and measured by flow cytometry. Results. In vitro study showed intracellular Adriamycin accumulation was remarkably increased by UA. Cell viability treated with Adr (4 μM) was decreased from 89.8% ± 4.7 to 32% ± 8.9 by combined with UA (4 μM). Adr-induced apoptosis and G1/G0 phase cell cycle arrest were remarkably increased by UA, as well as, intracellular ROS level. However, MDR reversing activity of UA was inhibited by N-acetyl cysteine (NAC), a ROS scavenger. Conclusion. These data provide compelling evidence that UA is a promising agent against MDR in leukemia cell line and suggest a promising therapeutic approach for leukemia.
http://bit.ly/2GhCk85
Microsatellite Markers Reveal Genetic Diversity and Relationships within a Melon Collection Mainly Comprising Asian Cultivated and Wild Germplasms
Melon, Cucumis melo L., is an important horticultural crop with abundant morphological variability, but the genetic diversity and relationships within wild and cultivated melons remain unclear to date. In this study, thick-skinned (TC) (cultivated subspecies melo), thin-skinned (TN) (cultivated subspecies agrestis), and wild accessions were analyzed for genetic diversity and relationships using 36 microsatellite markers. A total of 314 alleles were detected with a mean allelic number of 8.72 and polymorphism information content of 0.67. Cluster analysis of the accessions resulted in four distinct clusters (I, II, III, and IV) broadly matching with the TC, TN, and wild groups. Cluster I contained only two Indian wild accessions. Cluster II was consisted of 49 South Asian accessions, 34 wild accessions, and 15 TN accessions. Cluster III was a typical TC group including 51 multiorigin TC accessions and one wild accession. The remaining 88 accessions, including 75 TN accessions, 6 wild accessions, and 7 TC accessions, formed the cluster IV, and all the TN and wild accessions in this cluster were from China. These findings were also confirmed by Principal component analysis and STRUCTURE analysis. The South Asian subspecies agrestis accessions, wild and cultivated, had close genetic relationships with a distinctive genetic background. Chinese wild melons showed closeness to cultivated subspecies agrestis landraces and could be a return from the indigenous cultivated melons. The AMOVA and pairwise F statistics () presented genetic differentiation among the three groups, with the strongest differentiation ( = 0.380) between TC and TN melons. These results offer overall information on genetic diversity and affiliations within a variety of melon germplasms and favor efficient organization and utilization of these resources for the current breeding purpose.
http://bit.ly/2I4p1cx
Late Response of Antiretroviral Therapy in an HIV-1-Infected Patient due to Hepatitis B and C Coinfections: The First Case Report in Nepal
Aim. Dual coinfection of HCV and HBV in HIV-1-infected population is a leading cause of morbidity and mortality. Also, they share routes of HIV transmission; however, it might be associated with an independent factor like injecting drug use for HCV and unsafe sex for HBV. This case report suggests that hepatitis virus coinfection may lead to late response of antiretroviral therapy (ART) in HIV-1 patients. Patients and Methods. A 49-year-old male patient visited for the routine follow-up investigation at the National Public Health Laboratory (NPHL), Teku, Nepal. He was an HIV-1-positive injecting drug user (IDU) co-infected with HCV and HBV. The patient was under ART as per the National HIV Testing and Treatment Guidelines 2017, Nepal. Further, serological and viral load testing was performed for confirmation and monitoring therapy, respectively. Results. It is the first report that highlights the dual coinfection of HCV and HBV in an HIV-1 patient from Nepal. The follow-up investigation shows improved response to ART with an increase in CD4+ cells. However, detectable viral loads indicated for a late response might be due to effects of coinfections or viral interactions. Conclusions. Dual coinfection is rare; however, it is more serious with poorly defined epidemiology and evolution in an HIV-1-infected population. Thus, universal screening of HBV or/and HCV coinfection in HIV-1-infected population requires immediate implementation for true prevalence, proper management, and early intervention.
http://bit.ly/2WTQe5i
Molecular heterogeneity and early metastatic clone selection in testicular germ cell cancer development
https://go.nature.com/2tg7h3Z
Tumour cell blebbing and extracellular vesicle shedding: key role of matrikines and ribosomal protein SA
https://go.nature.com/2USFIJK
Could omega-3 fatty acids help prevent miscarriages?
A new study in mice reveals that omega-3s, a type of fat found in fish oil, reduces fetal and neonatal deaths, suggesting they could prevent some miscarriages in women.
http://bit.ly/2IeZSvM
High Expression of ANXA2 Pseudogene ANXA2P2 Promotes an Aggressive Phenotype in Hepatocellular Carcinoma
Objective. Accumulating evidence suggests that pseudogenes play potential roles in the regulation of their cognate wild-type genes, oncogenes, and tumor suppressor genes. ANXA2P2 (annexin A2 pseudogene 2) is one of three pseudogenes of annexin A2 that have recently been shown to be aberrantly transcribed in hepatocellular carcinoma (HCC) cells. However, its clinical meaning and biological function in HCC have remained unclear. Therefore, the present study was aimed at exploring the prognostic value of a high expression of ANXA2P2 in HCC tissue and at identifying whether it can affect the efficacy of targeted drugs (sorafenib, regorafenib, and lenvatinib). Methods. We obtained ANXA2P2 mRNA expression levels from The Cancer Genome Atlas (TCGA) RNA sequence database. The expression levels of ANXA2P2 in 49 pairs of intratumoral and peritumoral liver tissues were examined by RT-PCR. Wound healing and transwell assays were performed to confirm the tumor-promoting properties of ANXA2P2 in HCC cells. CCK8 assay was conducted to identify whether ANXA2P2 can affect the growth of HCC cells when administered with targeted drugs (sorafenib, regorafenib, and lenvatinib). Results. The expression of ANXA2P2 in HCC tissues was significantly higher than that in adjacent cancerous tissues from TCGA database and validation group. Additionally, patients with high ANXA2P2 expression in HCC tissue had a shorter overall survival, whereas no statistically significant correlation was found between ANXA2P2 expression and disease-free survival () as well as other clinical parameters, such as age, gender, histological grade, T classification, stage, albumin level, alpha-fetoprotein, and vascular invasion (, 0.8807, 0.5762, 0.8515, 0.7113, 0.242, 1.0000, and 0.7685, respectively). Furthermore, in vitro experiments showed that knockdown of ANXA2P2 inhibited migration and invasion of HCC cells but did not have an influence on the HCC cell proliferation when treated with targeted drugs (sorafenib, regorafenib, and lenvatinib). Conclusion. Our study confirmed elevated ANXA2P2 expression levels in HCC tissue compared with adjacent noncancerous tissue and a worse prognosis of patients with high ANXA2P2 levels in the HCC tissue. The newly found properties of promoting migration and invasion of ANXA2P2 in HCC help to explain this phenomenon. ANXA2P2 could be a novel and suitable predicative biomarker for the risk assessment of recurrence or metastasis of HCC patients but may not be effective to predict the efficacy of targeted drugs.
http://bit.ly/2GBWM2D
EMCrit Podcast 240 – Renal Compartment Syndrome & It’s all about the Venous Side and We’ve Been Fracking it up for Years
Renal Compartment Syndrome, Venous Congestion, CHF, and POCUS.
EMCrit Project by Scott Weingart.
http://bit.ly/2TIvf3c
Cost-effectiveness of microdiscectomy versus endoscopic discectomy for lumbar disc herniation
Publication date: Available online 10 February 2019
Source: The Spine Journal
Author(s): Kyung-Chul Choi, Hyeong-Ki Shim, Jin-Sung Kim, Kyung Han ChaMD, Dong Chan Lee, Ea Ran Kim, Mee Jung Kim, Choon-Keun Park
Background Context
Microdiscectomy is a standard technique for the surgical treatment of lumbar disc herniation (LDH). Endoscopic discectomy (ED) is another surgical option that has become popular owing to reports of shorter hospitalization and earlier return to work. No study has evaluated health care costs associated with lumbar discectomy techniques and compared cost-effectiveness.
Purpose
To assess the cost-effectiveness of four surgical techniques for LDH: microdiscectomy (MD), transforaminal endoscopic lumbar discectomy (TELD), interlaminar endoscopic lumbar discectomy (IELD), and unilateral biportal endoscopic discectomy (UBED).
Study design and setting
: Retrospective analysis.
Patient sample
: Patients who underwent either MD and ED for primary LDH with 1-year follow-up between the ages of 20 and 60 years old.
Outcome measures
: Incremental cost-effectiveness ratio (ICER).
Methods
Five hundred sixty-five patients aged 20-60 years who underwent treatment using one of the four surgical techniques with at least 1-year follow-up were reviewed. Health care costs were defined as the sum of direct and indirect costs. The former included the covered and uncovered costs of the National Health Insurance from operation to 1-year follow-up; indirect costs included costs incurred by work loss. Direct and indirect costs were evaluated separately. ICER was determined using cost/quality-adjusted life year (QALY). Health care costs and ICER were compared statistically among the four surgical groups. Cost-effectiveness was compared statistically between MD and ED.
Results
One hundred fifty-seven patients who underwent TELD, 132 for IELD, 140 for UBED, and 136 for MD were enrolled. The direct costs of TELD, IELD, UBED, and MD were $3,452.2±1,211.5, $3,907.3±895.3, $4,049.2±1,134.6, and $4,302.1±1,028.9, respectively (p<0.01). The indirect costs of TELD, IELD, UBED, and MD were $574.5±495.9, $587.8±488.3, $647.4±455.6, and $759.7±491.7, respectively (p<0.01). The 1-year QALY gains were 0.208 for TELD, 0.211 for IELD, 0.194 for UBED, and 0.186 for MD. ICER (costs/QALY) was the highest for MD ($34,840.4±25,477.9, p<0.01). Compared with MD, ED saved an additional net of $8,064 per QALY (p<0.01). There was no significant difference in the ICERs among the three endoscopic techniques.
Conclusions
ED was more cost-effective compared with MD at 1-year follow up.
http://bit.ly/2Bu5P26
Malpractice claims in spine surgery in Germany: a 5-year analysis
Publication date: Available online 10 February 2019
Source: The Spine Journal
Author(s): Sebastian A. Ahmadi, Hosai Sadat, Kai-Michael Scheufler, Hans-Jakob Steiger, Beate Weber, Thomas Beez
Abstract
Study Design
Retrospective analysis of anonymized malpractice claims.
Summary of Background Data
Spine surgery is considered a high-risk specialty with regards to malpractice claims. However, limited data is available for Germany. We analyzed the rate, subject and legal outcome of malpractice claims faced by spine surgeons in one of the largest Medical Council coverage areas in Germany, representing 60,000 physicians and a population of 10 million.
Methods
Analysis of all malpractice claims regarding spinal surgeries completed by the Review Board (RB) of the North Rhine Medical Council (NRMC) from 2012-2016. Claim merit, content and actual treatment errors were reviewed. Severity of damage was graded from negligible (1) to death (6).
Results
A total of 8,381 malpractice cases were reviewed by the NRMC from 2012-2016. Four percent (340 cases: 181 females, 159 males) pertained to patients undergoing spinal surgery with 94.7% of patients undergoing in-hospital treatment and 5.3% as outpatients. Malpractice claims most frequently involved neurosurgery (48.5%) and orthopedic surgery (37.6%). Trauma surgery was involved in 9.1% and other specialties in 4.8%. Actual treatment errors were found in 89 of 340 cases (26.2%).Of those, 81 resulted in treatment-associated health impairment. Negligible and/or temporary impairment was found in 49.3%. Negligible to moderate but permanent damage was observed in 39.5%. Nine patients suffered severe permanent damage or death (11.1%). The treated diagnosis was degenerative disc disease in 34 patients (41.9%), spinal canal stenosis in 13 (16%), vertebral body fractures in 10 (12.3%), spondylolisthesis in 6 (7.4%), and other diagnoses accounting for the remaining 18 (22.2%). Errors involved actual surgical treatment in 40.7%, surgical indication and pre-operative workup in 28.4%, postoperative treatment in 25.9%, and patient consent in 4.9%.
Conclusion
Spinal surgery claims account for 4% of all claims reviewed by the NRMC in the 5-year period from 2012 to 2016. Eighty-nine (26.2%) were deemed justified. The majority of treatment errors (59.3%) occurred during workup, indication and consent, or during postoperative care. Errors during actual surgery were responsible for 40.7% of all treatment-associated damages. Understanding the distribution and content of claims is key to improving patient satisfaction not only by honing surgical skills, but also by improving pre- and post-operative communication and care.
http://bit.ly/2TGT63r
Metformin Use and Lung Cancer Risk in Diabetic Patients: A Systematic Review and Meta-Analysis
Background. Antidiabetic medications (ADMs) can alter the risk of different types of cancer, but the relationship between lung cancer incidence and metformin remains controversial. Our aim was to quantitatively estimate the relationship between incidences of lung cancer and metformin in patients with diabetes in this meta-analysis. Methods. We performed a search in PubMed, Embase, ISI Web of Science, and Cochrane Library until September 20, 2017. The odds ratio (OR), relative risk (RR) or hazard ratio (HR), and 95% confidence interval (95% CI) were estimated using the random-effect model. The Newcastle-Ottawa Scale (NOS) was used to assess the study quality. Results. A total of 13 studies (10 cohort studies and 3 case-control studies) were included in the meta-analysis. Compared to nonmetformin users, metformin probably decreased lung cancer incidence in diabetic patients (; 95% CI, 0.83-0.96; ) with significant heterogeneity (,%, ). Subgroup analysis showed that cohort studies (; 95% CI, 0.85-0.98; ), location in Europe (; 95% CI, 0.86-0.94; ), the control drug of the sulfonylurea group (; 95% CI, 0.86-0.96; ), and adjusting for smoking (; 95% CI, 0.75-1.00; ) may be related to lower lung cancer risk. No significant publication bias was detected using a funnel plot. Conclusion. Metformin use was related to a lower lung cancer risk in diabetic patients compared to nonusers, but this result was retrieved from observational studies and our findings need more well-designed RCTs to confirm the association.
http://bit.ly/2SkN0cl
Jwa Kum Whan Attenuates Nonalcoholic Fatty Liver Disease by Modulating Glucose Metabolism and the Insulin Signaling Pathway
Over the last decade, the link between nonalcoholic fatty liver disease (NAFLD) and insulin resistance has attracted considerable attention. Caused by chronic hyperglycemic stress, insulin resistance (IR) impairs insulin signal transduction and leads to the development of NAFLD. Jwa Kum Whan (JKW), a herbal formula in Traditional Korean Medicine, consists of two medicinal herbs that possess notable effects against hyperglycemia and IR. In this study, we sought to determine the pharmacological effects of JKW, and the mechanisms responsible, on hepatic steatosis in free fatty acids (FFAs)-stimulated HepG2 cells and in high-fat diet (HFD)-fed obese mice. Treatment with JKW significantly decreased intracellular lipid accumulation in vitro. Furthermore, JKW significantly triggered the phosphorylation of insulin receptor substrate-1 (IRS-1) and phosphoinositide 3-kinase (PI3K) and modulated glucose and lipid metabolism via an AMP-activated protein kinase (AMPK) signaling pathway. Analysis of serum parameters in HFD-fed mice showed that JKW improved glucose levels and insulin resistance index (HOMA-IR). In addition, JKW successfully reduced hepatic triglyceride (TG) and cholesterol accumulation. Our results suggest that JKW alleviates NAFLD by modulating the insulin signaling pathway and glucose metabolism. These findings provide a scientific rationale for the potential use of JKW for the treatment and prevention of NAFLD.
http://bit.ly/2DoAoXo
Dopamine metabolism of the nucleus accumbens and fronto-striatal connectivity modulate impulse control
http://bit.ly/2UQXahs
Effect of Premedication on the Success of Inferior Alveolar Nerve Block in Patients with Irreversible Pulpitis: A Systematic Review of the Literature
Background. Failure in the provision of inferior alveolar nerve block anesthesia (IANB) is a significant problem during endodontic treatment of irreversible pulpitis. Various methodologies have been advocated one of which is administration of premedication prior to anesthesia. Despite the considerable number of reports, the topic yet deserves more clarification. This systematic review was conducted to provide an oversight on the effectiveness of premedication prior to IANB in mandibular teeth. Methods. A PubMed and Cochrane Database search was conducted by using MeSH terms inferior alveolar nerve block + pulpitis and mandibular anesthesia+pulpitis. Two reviewers independently performed the screening, selection of papers, and data extraction. Papers in English language that included randomized clinical studies on the impact of different medications on the success of inferior alveolar block anesthesia in irreversible pulpitis were included. Additionally, relevant supporting literature was also used where necessary. Results. Initially, 118 papers were selected from PubMed and 68 were selected from Cochrane. Five additional articles were retrieved from Google Search. Following the elimination of duplicates and irrelevant articles, 35 studies were selected meeting the criteria. It was observed that there was moderate evidence to suggest that some premedications were partially effective for the enhancement of mandibular anesthetic effect in irreversible pulpitis. Conclusion. Though some medications appear to be promising, further supporting research will help highlight this significant topic which requires further clarification.
http://bit.ly/2UT0hpr
Effect of eNOS on Ischemic Postconditioning-Induced Autophagy against Ischemia/Reperfusion Injury in Mice
Autophagy is involved in the development of numerous illnesses, including ischemia/reperfusion (I/R). Endothelial nitric oxide synthase (eNOS) participates in the protective effects of ischemic postconditioning (IPostC). However, it remains unclear whether eNOS-mediated autophagy serves as a critical role in IPostC in the hearts of mice, in protecting against I/R injury. In the present study, the hearts of mice with left anterior descending coronary artery ligation were studied as I/R models. H9c2 cells underwent exposure to hypoxia/reoxygenation (H/R) and were examined as in vitro model. IPostC reduced mice myocardial infarct size and improved the structure of the heart. IPostC increased the formation of autophagosomes and increased the phosphorylation of eNOS and adenosine monophosphate-activated protein kinase (AMPK). Autophagy and eNOS inhibition suppressed the cardioprotective effects of IPostC. AMPK or eNOS inhibition abolished the improvement effect of IPostC on autophagy. AMPK inhibition decreased eNOS phosphorylation in the heart. Additionally, H9c2 cells suffering hypoxia were used as in vitro model. Autophagy or eNOS inhibition abolished the protective effects of hypoxic postconditioning (HPostC) against H/R injury. AMPK and eNOS inhibition/knockout decreased autophagic activity in the HPostC group. These results indicated that IPostC protects the heart against I/R injury, partially via promoting AMPK/eNOS-mediated autophagy.
http://bit.ly/2tbIEFw
Recognition of a New Cr(VI)-Reducing Strain and Study of the Potential Capacity for Reduction of Cr(VI) of the Strain
The biotransformation of hexavalent chromium [Cr(VI)] via Cr(VI)-reducing microorganisms is considered an ecofriendly approach to detoxify Cr(VI). A new Cr(VI)-reducing bacterium named Microbacterium sp. QH-2 was isolated in this study. Scanning electron microscopy (SEM) images showed protrusions on the bacterial surface of strain QH-2 after an 18 h incubation in media under 10 mM Cr(VI) treatment. Results of the experiments on the capacity of reducing Cr(VI) indicated that strain QH-2 could reduce 100% Cr(VI) less than 48-96 h. When media with 4 mM Cr(VI) were incubated, the fastest reduction rate of strain QH-2 could come up to 2.17 mg/L Cr(VI) h−1. Furthermore, strain QH-2 could reduce Cr(VI) over the pH between 7 and 10. The optimum pH to reduce Cr(VI) by strain QH-2 was 9. Strain QH-2 also exhibited a relatively high tolerance even to 20 mM Cr(VI). These results declared that strain QH-2 had the potential to detoxify Cr(VI) in the Cr(VI)-contaminated soil or effluent.
http://bit.ly/2USZJjn
Geometric Morphology of the Coracoacromial Ligament: A Cadaveric Study
The coracoacromial ligament (CAL), which restrains superior displacement of humeral head, connects the acromion and coracoid process. Due to the ligament's variations and its role in shoulder pain, CAL was investigated in this study. Sixty shoulders of 34 cadavers, from persons aged 61-98 (80.95 ± 8.81) years at death time, were dissected. The lengths of lateral (LBL) and medial borders (MBL), widths of acromial (AIW) and coracoid insertions (CIW), and thicknesses of lateral (LSTAI) and medial (MSTAI) sides of acromial insertions were measured by digital caliper. The data were subjected to statistical analysis. 24 (40%) V-shaped, 12 (20%) broad-banded, 9 (15%) quadrangular, 9 (15%) Y-shaped, and 6 (10%) multiple-banded types were identified. The mean total LBL, MBL, AIW, CIW, LSTAI, and MSTAI were 34.94 ± 4.59 mm, 33.58 ± 5.31 mm, 29.82 ± 9.48 mm, 12.62 ± 3.95 mm, 1.29 ± 0.17 mm, and 0.90 ± 0.22 mm, respectively. The mean LBL (39.12 ± 4.29 mm), MBL (36.48 ± 3.9 mm), and CIW (37.01 ± 3.39 mm) were significantly greatest in quadrangular type (p
http://bit.ly/2teRtyc
Seizures and Blurred Vision as Initial Presentation of Intracerebral Schwannoma: A Rare Tumor of the Brain
Schwannomas are the most common tumor of peripheral nerves which are arising from Schwann cells and are benign in their nature. Intracranial schwannoma accounts for between 5 and 8% of intracranial tumors, whereas intracerebral schwannoma, a rare disease, accounts for
http://bit.ly/2GAcZFA
A Novel Heterozygous Mutation of the COL4A3 Gene Causes a Peculiar Phenotype without Hematuria and Renal Function Impairment in a Chinese Family
Mutations in the COL4A3 gene are frequently reported to be associated with various types of hereditary nephropathy. COL4A3 encodes the α3 chain of type IV collagen, which is the main structural protein in the basement membrane. Mutations in this gene are always related to kidney performance, and deafness and ocular lesion have also been reported. In this study, using next-generation sequencing, we investigated the DNA of a family visiting a clinic for hearing loss. A new missense mutation was found in COL4A3 of 5 patients, c.3227C>T (p.P1076L). Based on these results, we predict that the mutation is pathogenic and leads to abnormal collagen IV. Here, we report for the first time on this autosomal dominant syndrome, characterized by hearing loss and eye abnormalities, but without renal damage, in all carriers. Since the oldest patient in the trial was less than 50 years old, however, we recommend that renal examination be reviewed regularly. Our results reveal expansion in the mutation spectrum of the COL4A3 gene and phenotypic spectrum of collagen IV disease. Our study suggests that next-generation sequencing is an economical and effective method and may help in the accurate diagnosis and treatment of these patients.
http://bit.ly/2RUymDq
Cancers, Vol. 11, Pages 203: Utility of FIB4-T as a Prognostic Factor for Hepatocellular Carcinoma
Cancers, Vol. 11, Pages 203: Utility of FIB4-T as a Prognostic Factor for Hepatocellular Carcinoma
Cancers doi: 10.3390/cancers11020203
Authors: Kazuya Kariyama Kazuhiro Nouso Hidenori Toyoda Toshifumi Tada Atsushi Hiraoka Kunihiko Tsuji Ei Itobayashi Toru Ishikawa Akiko Wakuta Ayano Oonishi Takashi Kumada Masatoshi Kudo on behalf of the Real-Life Practice Experts for HCC (RELPEC) Study Group HCC 48 Group
Background: Most integrated scores for predicting the prognosis of patients with hepatocellular carcinoma (HCC) comprise tumor progression factors and liver function variables. The FIB4 index is an indicator of hepatic fibrosis calculated on the basis of age, aspartate aminotransferase (AST) levels, alanine aminotransferase (ALT) levels, and platelet count, but it does not include variables directly related to liver function. We propose a new staging system, referred to as "FIB4-T," comprising the FIB4 index as well as tumor progression factors, and examine its usefulness. Method: Subjects included 3800 cases of HCC registered in multiple research centers. We defined grades 1, 2, and 3 as a Fibrosis-4 (FIB4) index of <3.25, 3.26–6.70, and >6.70 as FIB4, respectively, and calculated the FIB4-T in the same manner in which the JIS (Japan Integrated Staging Score) scores and albumin-bilirubin tumor node metastasis (ALBI-T) were calculated. We compared the prognostic prediction ability of FIB4-T with that of the JIS score and ALBI-T. Results: Mean observation period was 37 months. The 5-year survival rates (%) of JIS score (0/1/2/3/4/5), ALBI-T (0/1/2/3/4/5) and FIB4-T (0/1/2/3/4/5) were 74/60/36/16/0, 82/66/45/22/5/0 and 88/75/65/58/32/10, respectively. Comparisons of the Akaike information criteria among JIS scores, ALBI-T, and FIB4-T indicated that stratification using the FIB4-T system was comparable to those using ALBI-T and JIS score. The risk of mortality significantly increased (1.3–2.8 times/step) with an increase in FIB4-T, and clear stratification was possible regardless of the treatment. Conclusion: FIB4-T is useful in predicting the prognosis of patients with HCC from a new perspective.
http://bit.ly/2BnO4lh
Cancers, Vol. 11, Pages 204: Non-Smoking-Associated Lung Cancer: A distinct Entity in Terms of Tumor Biology, Patient Characteristics and Impact of Hereditary Cancer Predisposition
Cancers, Vol. 11, Pages 204: Non-Smoking-Associated Lung Cancer: A distinct Entity in Terms of Tumor Biology, Patient Characteristics and Impact of Hereditary Cancer Predisposition
Cancers doi: 10.3390/cancers11020204
Authors: Smolle Pichler
Non-small cell lung cancer (NSCLC) in non-, and especially in never-smoking patients is considered a biologically unique type of lung cancer, since risk factors and tumorigenic conditions, other than tobacco smoke, come into play. In this review article, we comprehensively searched and summarized the current literature with the aim to outline what exactly triggers lung cancer in non-smokers. Changes in the tumor microenvironment, distinct driver genes and genetic pathway alterations that are specific for non-smoking patients, as well as lifestyle-related risk factors apart from tobacco smoke are critically discussed. The data we have reviewed highlights once again the importance of personalized cancer therapy, i.e., careful molecular and genetic assessment of the tumor to provide tailored treatment options with optimum chances of good response—especially for the subgroups of never-smokers.
http://bit.ly/2TFJ6aE
Cancers, Vol. 11, Pages 205: Mechanistic Modelling of Radiation Responses
Cancers, Vol. 11, Pages 205: Mechanistic Modelling of Radiation Responses
Cancers doi: 10.3390/cancers11020205
Authors: McMahon Prise
Radiobiological modelling has been a key part of radiation biology and therapy for many decades, and many aspects of clinical practice are guided by tools such as the linear-quadratic model. However, most of the models in regular clinical use are abstract and empirical, and do not provide significant scope for mechanistic interpretation or making predictions in novel cell lines or therapies. In this review, we will discuss the key areas of ongoing mechanistic research in radiation biology, including physical, chemical, and biological steps, and review a range of mechanistic modelling approaches which are being applied in each area, highlighting the possible opportunities and challenges presented by these techniques.
http://bit.ly/2BtyGUq
Relevance of Topographic Parameters on the Adhesion and Proliferation of Human Gingival Fibroblasts and Oral Bacterial Strains
Dental implantology allows replacement of failing teeth providing the patient with a general improvement of health. Unfortunately not all reconstructions succeed, as a consequence of the development of infections of bacterial origin on the implant surface. Surface topography is known to modulate a differential response to bacterial and mammalian cells but topographical measurements are often limited to vertical parameters. In this work we have extended the topographical measurements also to lateral and hybrid parameters of the five most representative implant and prosthetic component surfaces and correlated the results with bacterial and mammalian cell adhesion and proliferation outcomes. Primary human oral gingival fibroblast (gum cells) and the bacterial strains: Streptococcus mutans, Streptococcus sanguinis and Aggregatibacter actinomycetemcomitans, implicated in infectious processes in the oral/implant environment were employed in the presence or absence of human saliva. The results confirm that even though not all the measured surface is available for bacteria to adhere, the overall race for the surface between cells and bacteria is more favourable to the smoother surfaces (nitrided, as machined or lightly acid etched) than to the rougher ones (strong acid etched or sandblasted/acid etched).
http://bit.ly/2TDlxyZ
A potential contribution of decreased galectin‐7 expression in stratified epithelia to the development of cutaneous and esophageal manifestations in systemic sclerosis
Abstract
Backgrounds
Stratified epithelia have caught much attention as potential contributors to the development of dermal and esophageal fibrosis in systemic sclerosis (SSc). Galectin‐7 is a marker of all types of stratified epithelia, which is involved in the maintenance of epidermal homeostasis. So far, the role of galectin‐7 has not been studied in SSc.
Objectives
To investigate the potential contribution of galectin‐7 to the development of clinical manifestations in SSc.
Methods
Galectin‐7 expression was examined in skin samples and cultured keratinocytes by immunostaining and/or quantitative reverse transcription PCR. Serum galectin‐7 levels were determined by enzyme‐linked immunosorbent assay in 63 SSc and 20 healthy subjects.
Results
Galectin‐7 expression was markedly decreased in the epidermis of SSc lesional skin compared with that of healthy control skin. Serum galectin‐7 levels were significantly lower in SSc patients than in healthy controls, and inversely correlated with skin score. In addition, SSc patients with diffuse pigmentation and those with esophageal dysfunction had significantly decreased serum galectin‐7 levels as compared to those without each symptom. Importantly, endothelin‐1 stimulation suppressed galectin‐7 expression in normal human keratinocytes, and bosentan, a dual endothelin receptor antagonist, reversed circulating galectin‐7 levels and epidermal galectin‐7 expression in SSc patients.
Conclusions
Galectin‐7 down‐regulation in stratified epithelia, which is mediated at least partially by autocrine endothelin stimulation, may contribute to the development of cutaneous manifestations and esophageal dysfunction in SSc patients.
This article is protected by copyright. All rights reserved.
http://bit.ly/2GomCYT
Clinico-Pathological Correlation
| Correlation between total serum bilirubin and clinico-laboratory parameters of babies admitted for neonatal jaundice in a resource-limited setting Uchenna Ekwochi, Chidiebere D.I Osuorah, Ikenna Kingsley Ndu International Journal of Clinicopathological Correlation 2018 2(2):21-26 Background: Neonatal jaundice (NNJ) is one of the most frequent reasons newborn babies in low- to middle-income countries visit the hospital during the neonatal period. If not promptly managed, it could lead to serious neurological sequela and mortality. The level and type of bilirubin in serum are an important determinant of the management option in NNJ. Unfortunately, this simple but fundamental investigation is not readily available in many hospitals in low- to middle-income countries, and where available, needs to be done serially, an expenditure most clients cannot afford. Methodology: This study enrolled 83 newborns admitted and managed for NNJ at the Enugu State University Teaching Hospital during an 18-month period. We report correlation between total serum bilirubin (TSB) and selected newborn clinical and laboratory parameters. Results: A total of 83 newborns were admitted for NNJ during the study. The mean TSB (mTSB) was 307 ± 145.2 μmol/L. Preterm infants (T = 0.462, P = 0.500), neonates with birth weight <2.5 kg (T = 0.219, P = 0.804), female neonate (T = 0.314, P = 0.578), and those that presented with skin level at the lower body region (T = 28.52, P = 0.001) had a higher mTSB at presentation to the special care baby unit. Similarly, mTSB at presentation was higher in neonates with PCV <40% (T = 0.005, P = 0.942), negative malaria parasite film (T = 0.01, P = 0.933), and those that were Glucose-6-Phosphate dehydrogenase deficient (T = 1.59, P = 0.221). Only skin level of jaundice at presentation was significantly correlated to the TSB (R = 0.818 P = 0.001) while gestational age (R = 0.096, P = 0.500), age at presentation (R = 0.197, P = 0.157), and birth weight (R = −0.107, P = 0.459) were not. Linear regression analysis showed that for every regional rise in skin level of jaundice (X), the TSB (Y) in μmol/L increases by a factor of 89.74 expressed in a regression equation as, Y = −10.66 + 89.74 X. Conclusions: The skin level of jaundice can be used as a rough guide in the estimation of total bilirubin in newborns with jaundice. This is especially useful in resource-limited setting where facilities for testing bilirubin level are lacking. |
| Bilateral oral leukoplakia: A case report and review on its potential for malignant transformation K Tupakula Pavan, Ankita Kar, S Reddy Sujatha, BK Devi Yashodha, Nagaraju Rakesh, V Shwetha International Journal of Clinicopathological Correlation 2018 2(2):27-30 Oral leukoplakia (OL) is considered as a most common potentially malignant disorder (PMD) affecting the mucosa of the oral cavity. With the passage of time, the definitions of OL kept evolving. Leukoplakia usually presents after the fourth decade of life and is one of the most common oral PMDs affecting the oral cavity. Based on the macroscopic features of OL, it can be classified into two subtypes: homogeneous and nonhomogeneous. |
| Clopidogrel-induced thrombotic thrombocytopenia after years of medication Rateesh Sareen, Menka Kapil, Piyush Mathur, Madhulika Sharma International Journal of Clinicopathological Correlation 2018 2(2):31-33 Thrombotic thrombocytopenic purpura (TTP) is a life threatening, fulminant disease characterized by fever, microangiopathy hemolytic anemia, thrombocytopenia, neurological signs and renal insufficiency. The real culprit is agglutinated platelets and fibrin which form micro thrombi, gets deposited in arterioles and capillaries without eliciting inflammatory response. The idiopathic cases of TTP are characterized by deficiency of ADAMTS-13 (a disintegrin and metalloprotease, with thrombospondin -1 like domains) metalloprotease activity. The use of antiplatelet drugs, the thienopyridine derivatives Clopidogrel & Ticlodipine, is associated with drug induced TTP. The literature studies indicate that most cases of thienopyridine associated TTP involve an antibody to ADAMTS-13 metalloprotease that cause thrombocytopenia and respond to therapeutic plasma exchange (TPE). We report a case of 59 year old male who was on Clopidogrel post coronary angioplasty since past five years. He presented to us with complaints of nose bleeding and renal insufficiency. The evaluation of this potentially fatal drug complication should be borne in mind by physicians for all patients receiving Clopidogrel treatment. |
| Endometrial osteocartilaginous metaplasia: A case report and review of the literature Yeo Yen Ching, Mihir Gudi, Josefa E.O Vella International Journal of Clinicopathological Correlation 2018 2(2):34-36 Rare cases of osseous metaplasia and a single case of cartilaginous metaplasia have been reported previously but no previously reported cases of osteo-cartilagenous metaplasia were found on searching the literature. Osteo-cartilagenous metaplasia is a benign lesion which may be treated successfully with hysteroscopy. Awareness of this condition by histopathologists is important in order to avoid misdiagnosis of endometrial malignant mixed mullerian tumour. The authors report a patient with endometrial osteo-cartilagenous metaplasia, describe the clinical and histological features and review the literature on this condition. |
Dermatology, Venereology, Leprology
| Medical device regulation in India: What dermatologists need to know Sandeep Lahiry, Rajasree Sinha, Suparna Chatterjee Indian Journal of Dermatology, Venereology, and Leprology 2019 85(2):133-137 |
| Subclinical atherosclerosis and cardiovascular markers in patients with lichen planus: A case–control study Soheila Nasiri, Afsaneh Sadeghzadeh-Bazargan, Reza Mahmoud Robati, Hamid Reza Haghighatkhah, Shima Younespour Indian Journal of Dermatology, Venereology, and Leprology 2019 85(2):138-144 Background: Lichen planus is an idiopathic and chronic inflammatory disease that affects the skin and the mucous membranes, and has been associated with an increased risk for cardiovascular diseases. Hyperhomocysteinemia has been regarded as a risk factor for atherosclerosis and cardiovascular diseases. Increased plasma fibrinogen levels are also associated with increased risk of myocardial infarction. Objective: The main aim of this study is the evaluation of common carotid artery mean intima media wall thickness, serum fibrinogen and homocysteine levels in patients with lichen planus. Methods: Forty-three patients with lichen planus and 43 age, gender and body mass index (BMI) matched healthy controls (from general population without the disease) were included in this study. Results: Compared to the healthy controls, patients had statistically significant greater mean intima media wall thickness of the common carotid artery. Moreover, a positive correlation was observed between lichen planus and increased serum homocysteine and c-reactive protein levels. Limitations: The main limitation of this study is the small sample size due to the time limitation and financial constraints. Conclusion: Early diagnosis of atherosclerosis in patients with lichen planus might afford better prophylaxis, including weight control and/or lipid profile monitoring. Measurement of the mean intima media wall thickness of the common carotid artery by duplex high-resolution B-mode ultrasound scanning could be beneficial as a valuable method for early diagnosis of atherosclerosis in lichen planus. |
| Psoriasis increases the risk of concurrent inflammatory bowel disease: A population-based nationwide study in Korea Jin Yong Lee, Sungchan Kang, Jung Min Bae, Seong Jin Jo, Seong-Joon Koh, Hyun-Sun Park Indian Journal of Dermatology, Venereology, and Leprology 2019 85(2):145-152 Background: The epidemiology of the association between psoriasis and inflammatory bowel disease is poorly defined and remains controversial. Aim: To evaluate the prevalence of inflammatory bowel disease in patients with psoriasis compared with the general population. Methods: We searched the nationwide health claims database between 2011 and 2015 and evaluated the prevalence of inflammatory bowel disease, including Crohn's disease and ulcerative colitis. Results: Prevalence of inflammatory bowel disease, Crohn's disease and ulcerative colitis in patients with psoriasis vs the general population in 2011 were 0.16, 0.05 and 0.12% vs 0.08, 0.03 and 0.06%, respectively, which increased significantly with time between 2011 and 2015. Patients with psoriasis consistently revealed higher standardized prevalence (age and sex adjusted) of inflammatory bowel disease, Crohn's disease and ulcerative colitis compared with the general population. Subgroup analysis revealed the highest risk of prevalent inflammatory bowel disease in patients younger than 19 years (crude odds ratio 5.33, 95% confidence interval 3.74–7.59). Severe psoriasis demonstrated higher odds of inflammatory bowel disease (odds ratio 2.96, 95% confidence interval 2.54–3.45) than mild psoriasis (odds ratio 1.68, 95% confidence interval 1.51–1.88). Limitations: Limited data for doing adjustment and cross-sectional study design. Conclusions: Psoriasis patients revealed higher risk of inflammatory bowel disease. In particular, young patients and those with severe psoriasis may require closer monitoring and comprehensive management. |
| Linking of psoriasis with osteopenia and osteoporosis: A cross-sectional study Antonio Martinez-Lopez, Gonzalo Blasco-Morente, Maria Sierra Giron-Prieto, Miguel Angel Arrabal-Polo, Maria Luque-Valenzuela, Juan de Dios Luna-Del Castillo, Jesus Tercedor-Sanchez, Salvador Arias-Santiago Indian Journal of Dermatology, Venereology, and Leprology 2019 85(2):153-159 Background/Purpose: Psoriasis is a multisystem disease which has been related to vitamin-D deficiency through chronic inflammation. This psoriasis-related inflammatory state and vitamin-D deficiency may induce bone mineral density loss. The purpose of this study is to assess the relationship of psoriasis with bone mineral density, by comparing psoriatic patients with healthy controls and patients with osteopenia/osteoporosis. Methods: A total of 185 subjects were studied; 58 psoriatic patients who had not been under systemic or biological treatment were included. Age, gender, body mass index, phosphocalcic metabolic parameters and hip and lumbar (L4) bone mineral density data were collected. These variables were compared with those collected in 61 healthy controls and 67 patients with osteopenia/osteoporosis. Results: Psoriatic patients showed worse hip and lumbar spine bone mineral density levels than healthy controls (P = 0.001) and better levels than osteoporotic patients (P < 0.001). Multivariate analysis demonstrated a negative association of age and a positive association of body mass index in hip bone mineral density in psoriatic patients. Limitations: The main limitations are those of cross-sectional studies, such as a lack of follow up period, and a male predominance in the psoriatic group, which is corrected employing a multivariate analysis with an adjusted model for confounding factors. Conclusions: Bone mineral density levels in psoriatic patients are situated halfway between healthy controls and patients with osteopenia/osteoporosis. In addition, the higher body mass index in patients with psoriasis appears to confer a protective effect against further development of lower bone mineral density. |
| A randomized study to evaluate the efficacy and effectiveness of two sunscreen formulations on Indian skin types IV and V with pigmentation irregularities Rashmi Sarkar, Vijay Kumar Garg, Annie Jain, Divya Agarwal, Anupama Wagle, Frederic Flament, Michèle Verschoore Indian Journal of Dermatology, Venereology, and Leprology 2019 85(2):160-168 Background: Regular exposure to ultraviolet rays is high in India, where most Indians present Fitzpatrick skin phototypes IV and V. Aims: To evaluate the efficacy and compare the effectiveness of two sunscreen products on Indian skin types IV and V with pigmentation irregularities. Methods: A randomized, uncontrolled and investigator-blinded, single-center study enrolled adult men and women (18–45 years) with Fitzpatrick skin phototypes IV (28° < individual typological angle <10°) and V (10° < individual typological angle < −30°) with pigmentary abnormalities seen on the face in adults (actinic lentigines and postinflammatory hyperpigmentation), who did not use sunscreens. Participants were randomized (1:1) to either of the two marketed sunscreen products, Product A (sun protection factor 50 PA+++) or Product B (sun protection factor 19 PA+++), applied twice daily before sun exposure for ≥2 h. Primary objectives aimed at assessing possible improvement in hyperpigmented spots and overall skin appearance after 12 weeks of use. Evaluation of skin radiance and skin color was done by means of L'Oréal color chart and colorimetric measurements (Chromameter®). Results: Among the 230 enrolled participants, 216 (93.91%) completed the study. The clinical assessment of the density of pigmented spots and skin radiance showed significant (P < 0.001) improvement in both groups during all visits. The qualitative (participant perception) and quantitative (Chromameter®) data indicated improvement in pigmentation from Week 0 to Week 12. Both products were well-tolerated. Limitations: The study was conducted over a rather short period of time (12 weeks) at a single location. Conclusions: This is the first study conducted on Indian skin phototypes IV and V under real-life conditions. It demonstrated the effect of regular sunscreen usage in the prevention of certain signs of skin photoaging such as increased pigmentation or pigmentary abnormalities, thus providing support and assistance to clinicians in suggesting the use of efficient sun-screening products to patients. |
| Crusted nipple and areola: A new aetiology of secondary hyperkeratosis of the nipple and areola Dhaifallah A Alenizi Indian Journal of Dermatology, Venereology, and Leprology 2019 85(2):169-170 Hyperkeratosis of the nipple and areola is a rare condition first described by Tauber in 1923. Less than 100 cases have been reported in the literature. Hyperkeratosis of the nipple and areola presents as hyperkeratotic, hyperpigmented plaques on the nipple and areola. It is more common in females. An 18-year-old female patient presented with hyperkeratotic, plaque-like, hard crusts on both nipples and areolas. The examining physician could successfully remove this crust using his finger. The crust had accumulated as a result of the patient's reluctance to touch or clean the breast area due to psychological issues. A crusted nipple and areola may occur as a secondary condition due to a patient's reluctance to touch or clean their breasts. |
| Primary mucinous carcinoma of skin with a trichoadenomatous component: A rare case report Athota Kavitha, Chennamsetty Kavya, Kovi Sneha, Chennamsetty Teja Indian Journal of Dermatology, Venereology, and Leprology 2019 85(2):171-174 Primary mucinous carcinoma of the skin is a rare subtype of eccrine sweat gland tumors. Differentiating it from metastatic adenocarcinomas is important in the management of this condition. We report the case of a 55-year-old female presenting with a painless nodule, which was subsequently diagnosed as primary mucinous carcinoma of skin with a trichoadenomatous component. The possibility of a metastatic adenocarcinoma was ruled out by performing ultrasound abdomen, total body computed tomography, mammogram and colonoscopy. |
| Ultrasound assessment of enthesis thickness in psoriasis and psoriatic arthritis: A cross-sectional study Dario Graceffa, Claudio Bonifati, Viviana Lora, Pier Luigi Saraceni, Catia De Felice, Maria Sole Chimenti, Roberto Perricone, Aldo Morrone Indian Journal of Dermatology, Venereology, and Leprology 2019 85(2):175-181 Background: The inflammatory involvement of the enthesis in the course of psoriasis is accompanied by structural abnormalities detectable by ultrasound. The most common of these abnormalities is the thickening of the tendon at the insertion site. Aims: The aim of the present study was to compare the thickness of entheses of patients with psoriatic arthritis, only skin psoriasis, and healthy controls. Methods: A cross-sectional study was conducted in a cohort of patients affected with either only skin psoriasis or psoriatic arthritis as well as in a control group. Eight entheses sites were scanned by ultrasound bilaterally. The following entheseal characteristics were collected and recorded in a predefined database: entheseal thickness, bone erosions, enthesis calcifications (enthesophytes), presence of blood flow, and presence of bursitis. All the detected entheseal changes were scored, and the data was statistically analyzed. Results: The major differences in enthesis thickness between only skin psoriasis and psoriatic arthritis patients were found at the following sites: (i) olecranon tuberosity, (ii) superior pole of the patella, and (iii) medial epicondyle of femur. The thickness of the medial collateral ligament at the site of the femoral origin was increased in psoriatic arthritis, but not in both only skin psoriasis and healthy controls. The score obtained by adding the thickness of all the 8 examined entheses for each patient showed significant differences among the three groups (psoriatic arthritis: 81.3; only skin psoriasis 74.4; Controls: 67.6; P < 0.0001). Interestingly, we found that in psoriatic arthritis patients, the highest enthesis thickening was seen in entheses affected by bone erosions. Limitations: The small sample of patients studied is a limiting factor in this study. Conclusions: Our data demonstrated that the ultrasound measurement of the enthesis thickness enables a distinction between patients with psoriatic arthritis from those with only skin psoriasis. It is a useful method to improve diagnostic accuracy, especially in patients without clear clinical signs of enthesitis. |
| An observational study on glabellar wrinkle patterns in Indians Amala Kamat, Trisha Quadros Indian Journal of Dermatology, Venereology, and Leprology 2019 85(2):182-189 Background: Botulinum A exotoxin is an established treatment for glabellar frown lines, crow's feet, and horizontal furrows of the forehead. The glabella is probably the most common site for botulinum toxin treatment in Asians. Five glabellar contraction patterns have been classified in earlier studies based on eyebrow approximation, depression, and elevation. Unfortunately, this was found to be confusing by many practitioners. Indians, as all Asians, have smaller muscles compared to the European population, and there is no consensus on the optimal dosage per injection site or concentration of toxin to be used. Aims: (a) Identification and classification of glabellar wrinkle patterns in Indians. (b) Optimization of the minimal effective dose of toxin per site. Materials and Methods: Retrospective photographic analysis of 200 patients who received botulinum toxin for the first time to treat glabellar wrinkles was conducted. The wrinkle patterns were identified and classified by the authors based on the prevalence of perpendicular and transverse glabellar lines, nasal, and forehead wrinkles. Results: Six patterns were identified: (1) 11 (2) U (3) Pi (4) X (5) W (6) I. The relevant muscles were identified and doses optimized for those sites. Limitations: The doses mentioned in this study are not universal for all patients and toxin units would have to be altered and individualized according to the bulk of the facial muscles and individual needs. Conclusion: The investigators classification, injection patterns, and dosage may provide valuable guidance to facial esthetic treatment. |
| Onychomatricoma: Clinical, dermoscopy and ultrasound findings Denise Gamé, Ane Jaka, Carlos Ferrándiz Indian Journal of Dermatology, Venereology, and Leprology 2019 85(2):190-191 |
Global Infectious Diseases
| State of the globe: Effect of pneumococcal conjugate vaccines on nonvaccine-type invasive pneumococcal disease Sunil Kumar Raina Journal of Global Infectious Diseases 2019 11(1):1-1 |
| Treating more with less: Effectiveness and event outcomes of antituberculosis fixed-dose combination drug versus separate-drug formulation (Ethambutol, Isoniazid, Rifampicin and Pyrazinamide) for pulmonary tuberculosis patients in real-world clinical practice Jacqueline Mui Lan Lai, Su Lan Yang, Richard Avoi Journal of Global Infectious Diseases 2019 11(1):2-6 Introduction: Conventionally, a combination of four separate drugs (ethambutol, isoniazid, rifampicin, and pyrazinamide [EHRZ]) is the first-line pharmacotherapy for pulmonary tuberculosis (TB). In recent years, fixed-dose combination (FDC) formulation, where a single tablet contains the active ingredients of four aforementioned drugs, is gaining popularity due to its ease of administration. Objective: To compare the real-world effectiveness of EHRZ and FDC treatment groups on a cohort registry by investigating the sputum conversion rate and treatment outcomes of both groups. Methods: A total of 11,489 patients' data were extracted from the Sabah TB registry between January 2012 and June 2016, including EHRZ (n = 4188) and FDC (n = 7301) patients. Then, 1:1 propensity score matching was adopted to reduce the baseline bias. Caliper matching was conducted with maximum tolerance score set at 0.001. Confounders included in the propensity score matching were gender, nationality, diabetes, HIV status, smoking status, and chest X-ray status. Successful matching provided 4188 matched pairs (n = 8376) for final analysis. Results: In this matched cohort of 4188 pairs, the 2-month sputum conversion rate of FDC group was significantly higher than the EHRZ group (96.3% vs. 94.3%; P < 0.001) whereas 6-month sputum conversion of both groups showed no significant difference. Treatment outcomes such as noncompliance rate, failure rate, and success rate have no significant difference (P > 0.05) in both the treatment groups. There was an incidental finding of reduced death rate among FDC group compared to the EHRZ group (0.2% vs. 0.5%; P = 0.034). Conclusion: The FDC formulation has better sputum conversion rate at 2 months compared to conventional EHRZ regime as separate-drug formulation. It was also observed that FDC has a slight protective effect against all-cause death among TB patients. This protective effect of FDC, however, still needs to be proven further. |
| Clinico-epidemiological study of viral acute encephalitis syndrome cases and comparison to nonviral cases in children from Eastern India Sandeep Kumar Tripathy, Pravakar Mishra, Bhagirathi Dwibedi, Lipsa Priyadarshini, Rashmi Ranjan Das Journal of Global Infectious Diseases 2019 11(1):7-12 Objectives: The objective is to study the clinico-epidemiological features of viral acute encephalitis syndrome (AES) cases and compare them with nonviral AES cases in children from Eastern India. Methods: This prospective observational study was conducted in the department of pediatrics of a tertiary care teaching hospital in Eastern India over 18-month period. Children (6 months to 15 years) with acute onset of fever (≥37.5°C) and a change in mental status (including symptoms such as confusion, disorientation, coma, or inability to talk) and/or new onset of seizures (excluding simple febrile seizures) were included in the study. The main outcome measures were the etiology and proportion attributed to viruses causing AES with clinical correlation. Results: Of 834 of clinically suspected AES cases, viral etiology could be confirmed in 136 (16.3%) cases (herpes simplex virus-1 [HSV-I] was most common). The 5–15 years' age group was most commonly affected (boys > girls). More cases occurred from July to November. The presence of rash and Glasgow Coma Scale <8 at admission was significantly higher in viral AES. During hospitalization, development of shock, ventilatory requirement, duration of stay, and mortality was significantly higher in viral AES. On neuroimaging, global cerebral injury was common in HSV, Japanese encephalitis, and varicella-virus AES. Conclusions: Viral etiology forms a significant proportion of pediatric AES. Morbidity and mortality are high in viral compared to nonviral AES. Herpes encephalitis (HSV-I) is the most common cause of pediatric AES in Eastern India. Viral AES has poor prognosis compared to nonviral AES. |
| Factors associated with mortality in immunocompetent patients with hospital-acquired pneumonia Pavaruch Sangmuang, Aroonrut Lucksiri, Wasan Katip Journal of Global Infectious Diseases 2019 11(1):13-18 Aim: The aim of the study is to determine the factors associated with 28-day mortality in immunocompetent patients with hospital-acquired pneumonia (HAP). Methods: This was a 42-month retrospective cohort study in Chiang Kham Hospital. Patients with HAP diagnosed between January 2013 and June 2016 who did not have an immunocompromised status were recruited into the study. Statistical Analysis Used: Univariable and multivariable binary logistic regression analyses were performed to determine the factors associated with mortality in patients with HAP. Results: A total of 181 HAP patients. The most causative pathogens were nonfermenting Gram-negative bacilli. Fifty-two (28.7%) patients had died within 28 days after HAP diagnosis. Multivariable analysis demonstrated that mechanical ventilation (MV) dependency (adjusted odds ratio [OR] = 3.58, 95% confidence interval [CI] 1.53–8.37, P = 0.003), antibiotic duration (adjusted OR = 0.79, 95% CI 0.70–0.88, P < 0.001), acute kidney injury (adjusted OR = 5.93, 95% CI 1.29–27.22, P = 0.022), and hematologic diseases (adjusted OR = 11.45, 95% CI 1.61–81.50, P = 0.015) were the significant factors associated with 28-day mortality. Conclusions: The factors associated with mortality were MV dependency, HAP duration of treatment, acute kidney injury, and hematologic disease. Early recognition of these factors in immunocompetent patients with HAP and treatment with intensive care may improve the outcome. |
| Co-infection of herpes simplex virus type 2 and HIV infections among pregnant women in Ibadan, Nigeria Chinenye Gloria Anaedobe, Tinuade Adesola Ajani Journal of Global Infectious Diseases 2019 11(1):19-24 Introduction: Genital infection with herpes simplex virus type 2 (HSV-2) facilitates the acquisition of HIV, both mutually reinforcing infection. Lifelong latent HSV-2 infection raises concerns among women of reproductive age, considering the risk of neonatal transmission. In Nigeria, screening for HSV-2 and co-infection with HIV in antenatal clinics is not routine. This study was undertaken to determine the seroprevalence and co-infection of HSV-2 and HIV among pregnant women. Methods: This was a cross-sectional study conducted at the antenatal clinic of the University College Hospital, Ibadan, between March and August 2013. A total of 270 consenting pregnant women were enrolled. The study involved collecting socio-demographic data and laboratory determination of HSV-2 immunoglobulin G (IgG) and HIV seroprevalence using type-specific third-generation enzyme-linked immunosorbent assay (DIAPRO Diagnostic Bioprobes, Milan, Italy) and Uni-Gold Recombigen/ALERE determine, respectively. Data analyses were done using SPSS version 20 (SPSS Inc., IL, USA). Results: The seroprevalence for HSV-2 type-specific IgG was 33.3% (90/270), and HIV antibodies were identified in 19.63% (53/270) of the women. The HIV co-infection was 38.8% (35/90) among HSV-2-positive women and 10% (18/180) among HSV-2-negative women. Majority of the HSV-2 positive women (62.2%, 56/90) presented in their 2nd trimester while 18.9% (17/90) in their 3rd trimester. Conclusion: The seroprevalence of HSV-2 in this pregnant population is lower than what is observed in some other Sub-Saharan African countries; however, HSV-2/HIV co-infection is high. The HSV-2-seronegative women are still susceptible to primary HSV-2 infection in pregnancy with increased risk for HIV co-infection and neonatal transmission. |
| Analysis of anti-toxoplasma immunoglobulin G and immunoglobulin M antibody levels after intervention with Curcuma Longa extract on early pregnant mice with acute toxoplasmosis Tigor Peniel Simanjuntak, Mochammad Hatta, Andi M Tahir, Robert H Sirait, Marni B Karo, Titus Tambaib, Ressy Dwiyanti, Rizki Amelia Noviyanthi, Ade Rifka Junita Journal of Global Infectious Diseases 2019 11(1):25-29 Background: Curcuma longa has strong anti-inflammatory effect. This study aims to evaluated the level of anti-Toxoplasma immunoglobulin G and immunoglobulin M (IgG-IgM) antibody after intervention with C. longa extract in early pregnant mice with acute toxoplasmosis. Materials and Methods: We evaluated 20 early pregnant mice that were divided into five groups, four mice in each. Group 1-4 received injections of Toxoplasma gondii tachyzoites. Three days later, G1 and G2 were given orally 125 mg/kg/day and 500 mg/kg/day of C. longa extract, respectively. G3 was given 60 mg/kg/day of spiramycin (positive control), and G4 was given 0.2 ml of distilled water (negative control). G5 underwent no intervention at all. Blood samples were obtained serially (before and 3 days after injection of tachyzoites, 3 days and 7 days after intervention) to assess anti-Toxoplasma IgG-IgM antibody levels by enzyme-linked immunosorbent assay methods. Results: Anti-Toxoplasma IgG-IgM antibody levels increased significantly 3 days after injection of tachyzoites (P < 0.05), but decreased significantly (P < 0.05) 3 days, and 7 days after administration of C. longa extract dose 125 mg, 500 mg, and spiramycin 60 mg, and there was no significant difference between these three groups. Anti-Toxoplasma IgG-IgM antibody levels increased significantly (P < 0.05) 3 days, 6 days, and 10 days after injections of tachyzoites on G4. The IgG-IgM antibody levels fluctuated on G5 and considered as insignificant (P > 0.05). Conclusion: The administration of C. longa extract at a dose of 125 mg/kg/day for 7 days effectively decreased anti-Toxoplasma IgG-IgM antibody level in early pregnant mice with acute toxoplasmosis. |
| Changes in the pneumococcal vaccine serotypes in adult noninvasive pneumonia after the introduction of pneumococcal conjugate vaccination for children Hiroaki Takeda, Chisa Sato, Chang Bin, Midori Nishidzuka, Mari Watanabe, Tomoka Yamamoto, Hiroki Suzuki, Kazunori Oishi, Fumihiro Tsuchida Journal of Global Infectious Diseases 2019 11(1):30-35 Context: Although the incidence of invasive pneumococcal infections in children has decreased since the introduction of pneumococcal conjugate vaccines (PCVs), the appearance of serotype replacements has continued to increase. Aims: We examined the frequency of serotype replacements in adult cases of pneumococcal pneumonia. Furthermore, the transition in the coverage of vaccine serotypes (VTs) to non-VTs (NVTs) was also examined. Settings and Design: We investigated all confirmed cases of pneumococcal pneumonia in 303 adult patients admitted to Yamagata Saisei Hospital between April 2006 and March 2015. Materials and Methods: Pneumococcal serotypes were determined by testing for a specific type of antiserum using the capsular swelling method. Statistical Analysis Used: Chi-square tests were used to compare patient characteristics. Results: Annually, the number of admitted patients ranged from 24 to 43, with most of them being men (64.7% of the total patient cohort). Although many cases involved some underlying conditions, the rate of pneumococcal vaccination remained low. The average rate of multigeneration housing was high (37.6%). The rates of pneumococcal vaccine coverage declined since 2013 (7-valent PCV (PCV7), 18.5%; PCV13, 59.3%; and 23-pneumococcal polysaccharide vaccine (PPSV23), 66.7%) and were <50% for each vaccine (PCV7, 4.7%; PCV13, 32.6%; and PPSV23, 48.8%) in 2015. In addition, the VTs were replaced with NVTs in 2015 (48.8% vs. 51.2%). Conclusions: The frequency of NVTs in adult pneumococcal pneumonia increased in 2013, with the frequency exceeding that of the vaccine forms in 2015. Regular PCV vaccination of children and multigeneration housing seem to be associated with this reversed trend. |
| Global contributors to antibiotic resistance Aastha Chokshi, Ziad Sifri, David Cennimo, Helen Horng Journal of Global Infectious Diseases 2019 11(1):36-42 Introduction: Antibiotic-resistant infections have become increasingly prevalent nowadays. As a result, it is essential to examine the key socioeconomic and political factors which contribute to the rise in the prevalence of antibiotic resistance in developing and developed nations. This study aims to identify the various contributors to the development of antibiotic resistance in each type of nation. Methods: PUBMED was used to identify primary research, systematic reviews, and narrative reviews published before Jan 2017. Search terms included antibiotic resistance, antimicrobial resistance, superbugs, multidrug-resistant organisms, developing countries, developed countries. Publications from different countries were included to ensure generalizability. Publications were excluded if they didn't mention factors causing resistance, focused on the molecular basis of resistance, or if they were case reports. Publicly available reports from national and international health agencies were used. Results: In developing countries, key contributors identified included: (1) Lack of surveillance of resistance development, (2) poor quality of available antibiotics, (3) clinical misuse, and (4) ease of availability of antibiotics. In developed countries, poor hospital-level regulation and excessive antibiotic use in food-producing animals play a major role in leading to antibiotic resistance. Finally, research on novel antibiotics is slow ing down due to the lack of economic incentives for antibiotic research. Conclusion: Overall, multiple factors, which are distinct for developing and developed countries, contribute to the increase in the prevalence of antibiotic resistance globally. The results highlight the need to improve the regulatory framework for antibiotic use and research globally. |
| Fatal oculocutaneous ecthyma gangrenosum in human immunodeficiency virus/acquired immunodeficiency syndrome: Case report and review of the literature Eshan B Henshaw, Affiong A Ibanga, Derima P Obaji Journal of Global Infectious Diseases 2019 11(1):43-46 Ecthyma gangrenosum (EG) is a rare, infective skin disease, predominantly but not exclusively caused by Pseudomonas aeruginosa. It is often seen in individuals with immunosuppression, although it has also been reported among previously healthy individuals. It was initially thought to be pathognomonic of P. aeruginosa septicemia, but this assertion was discarded following several reports on EG without bacteremia and EG with varied bacterial and fungal etiologies. There are scant reports of its association with human immunodeficiency virus (HIV) infection, while ocular involvement is extremely rare. An extensive search of the literature also found no report on EG, nor its relationship with HIV/acquired immunodeficiency syndrome (AIDS) from Sub-Saharan Africa. We hereby present a fatal case of multiple EG lesions in a 44-year-old Nigerian female with AIDS in the absence of bacteremia and review the literature of its association with HIV/AIDS and its concurrent orbital involvement. |
| Recurrence of Citrobacter koseri-associated intra-abdominal infection 2 years after spilled gallstones during laparoscopic cholecystectomy Kelly Cummings, Teresa Khoo, Timothy Pal, George Psevdos Journal of Global Infectious Diseases 2019 11(1):47-49 Spilled gallstones during laparoscopic cholecystectomy (LC) are common. Lost gallstones can lead to complications such as intra-abdominal abscesses, which can occur days, months, or even years after the procedure. Citrobacter koseri belongs to the family of Enterobacteriaceae. It is a low-virulence pathogen; however, it is linked to infections of the urinary tract and abdomen. We report the case of a 70-year-old diabetic male who presented with C. koseri- associated subhepatic abscess. Two years prior, he had emphysematous cholecystitis and liver abscess caused by C. koseri. During his LC, gallstones were spilled in the abdominal cavity and every effort was made to retrieve them. However, 2 years later, an aspiration of the subhepatic abscess revealed cholesterol fragments. We hypothesize that dislodged cholesterol gallstones and bile, contaminated with C. koseri, were the culprits for the appearance of the subhepatic abscess with the same organism 2 years after the LC. |
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
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