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Not All Rashes Are Allergic: Keratoderma Blennorrhagicum-Like Rash Masquerading as Contact Dermatitis.
Allergy Rhinol (Providence). 2018 Jan-Dec;9:2152656718811566
Authors: Li MY, Kolfenbach J, Schocket A
PMID: 30546925 [PubMed]
| Related Articles |
Not All Rashes Are Allergic: Keratoderma Blennorrhagicum-Like Rash Masquerading as Contact Dermatitis.
Allergy Rhinol (Providence). 2018 Jan-Dec;9:2152656718811566
Authors: Li MY, Kolfenbach J, Schocket A
PMID: 30546925 [PubMed]
| Related Articles |
Past and Present of Eye Movement Abnormalities in Ataxia-Telangiectasia.
Cerebellum. 2018 Dec 06;:
Authors: Tang SY, Shaikh AG
Abstract
Ataxia-telangiectasia is the second most common autosomal recessive hereditary ataxia, with an estimated incidence of 1 in 100,000 births. Besides ataxia and ocular telangiectasias, eye movement abnormalities have long been associated with this disorder and is frequently present in almost all patients. A handful of studies have described the phenomenology of ocular motor deficits in ataxia-telangiectasia. Contemporary literature linked their physiology to cerebellar dysfunction and secondary abnormalities at the level of brainstem. These studies, while providing a proof of concept of ocular motor physiology in disease, i.e., ataxia-telangiectasia, also advanced our understanding of how the cerebellum works. Here, we will summarize the clinical abnormalities seen with ataxia-telangiectasia in each subtype of eye movements and subsequently describe the underlying pathophysiology. Finally, we will review how these deficits are linked to abnormal cerebellar function and how it allows better understanding of the cerebellar physiology.
PMID: 30523550 [PubMed - as supplied by publisher]
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Cochrane corner: platinum-induced hearing loss after treatment for childhood cancer.
Int J Audiol. 2018 Dec 13;:1-4
Authors: Brennan-Jones CG, McMahen C, Van Dalen EC
Abstract
This Cochrane Corner features the review entitled "Platinum-induced hearing loss after treatment for childhood cancer" published in 2016. In their review, van As et al. identified 13 cohort studies including 2837 participants with a hearing test after treatment with a platinum-based therapy for different types of childhood cancers. All studies had problems related to quality of the evidence. The reported frequency of hearing loss varied between 1.7% and 90.1% for studies that included a definition of hearing loss; none of the studies provided data on tinnitus. Only two studies evaluated possible risk factors. One study found a higher risk of hearing loss in people treated with the combination of cisplatin plus carboplatin compared to treatment with cisplatin only and for exposure to aminoglycosides. The other found that age at treatment (lower risk in older children) and single maximum cisplatin dose (higher risk with an increasing dose) were significant predictors for hearing loss, while gender was not. This systematic review shows that children treated with platinum analogues are at risk of developing hearing loss, but the exact prevalence and risk factors remain unclear.
PMID: 30545270 [PubMed - as supplied by publisher]
47 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
These pubmed results were generated on 2018/12/14
PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
| Related Articles |
Optimized imaging of the lower abdomen and pelvic region in hepatocyte-specific MRI: evaluation of a whole-abdomen first-pass shuttle protocol in patients with neuroendocrine neoplasms.
Acta Radiol. 2018 Dec 12;:284185118817936
Authors: Fehrenbach U, Kahn J, Fahlenkamp U, Baur A, Pavel M, Geisel D, Denecke T
Abstract
BACKGROUND: Gadoxetic acid (Gd-EOB) has shown its advantages in hepatic tumor evaluation besides its disadvantages in extrahepatic staging due to its short hemodynamic interval. This results in the dilemma of which contrast agent to choose for whole abdominal magnetic resonance imaging (MRI).
PURPOSE: To evaluate the achievable contrast of a shuttle protocol for Gd-EOB MRI with accelerated 3D-T1-weighted sequences enabling complete dynamic liver imaging plus first-pass pelvic imaging.
MATERIAL AND METHODS: Seventy-four patients with abdominal neuroendocrine neoplasms were scanned with a protocol including a first-pass pelvic (pelvicFP) sequence in Gd-EOB MRI. Acquisition of this pelvicFP sequence was between portal venous and venous liver phase. Pelvic vessel and tissue enhancement was compared to a commonly acquired late/transitional phase sequence. In the same patients, liver enhancement was compared to a standard Gd-EOB protocol (n = 55) as well as to vessel contrast in previously acquired MRI with extracellular contrast medium (ECCM) (n = 14).
RESULTS: Pelvic vessel and lymph node enhancement showed significantly higher signal intensities (SI) in pelvicFP than in late phase sequences with Gd-EOB ( P < 0.001). Liver enhancement showed no significant differences compared to the standard protocol. Vessel enhancement in Gd-EOB pelvicFP showed significantly higher SI than an equilibrium phase sequence with ECCM ( P = 0.003-0.04).
CONCLUSION: Including a pelvicFP sequence between portal venous and venous liver phases is technically feasible and achieves improved contrast in the pelvis in Gd-EOB MRI. There was no quality loss in liver enhancement compared to a regular Gd-EOB liver examination. Gd-EOB pelvicFP vessel enhancement was not inferior to an equilibrium phase with ECCM.
PMID: 30541328 [PubMed - as supplied by publisher]
| Related Articles |
Association Between High Neutrophil to Lymphocyte Ratio and Delayed Recovery From Bell's Palsy.
Clin Exp Otorhinolaryngol. 2018 Dec 15;:
Authors: Kim HS, Jung J, Dong SH, Kim SH, Jung SY, Yeo SG
Abstract
Objectives: Factors predictive of the severity of and recovery from Bell's palsy remain unclear. This study evaluated the association between neutrophil to lymphocyte ratio (NLR) and the severity of and recovery from Bell's palsy.
Methods: This retrospective study included 51 patients who were hospitalized with Bell's palsy from 2015 to 2017. Degree of paralysis was assessed by House-Brackmann (H-B) grade. Patients with H-B grades 2-4 were classified as having mild to moderate palsy and patients with H-B grade 5 or 6 were classified as having severe palsy. Patients were evaluated for obesity, hypertension and diabetes mellitus, and blood tests were performed to determine NLR and platelet to lymphocyte ratio. Patients were treated with steroids and antiviral agents. H-B grade was assessed 1 week, 1 month, and 3 months after treatment.
Results: NLR was significantly higher in patients with severe than with mild to moderate palsy (P=0.048). Recovery time was significantly longer in patients with high NLR than low NLR (P=0.045).
Conclusion: Higher NLR in patients with Bell's palsy was associated with longer recovery time. NLR may be prognostic of recovery time in patients with Bell's palsy.
PMID: 30545211 [PubMed - as supplied by publisher]
| Related Articles |
Allergen-specific IgE and IgG4 patterns among patients with different allergic diseases.
World Allergy Organ J. 2018;11(1):35
Authors: Smoldovskaya O, Feyzkhanova G, Voloshin S, Arefieva A, Chubarova A, Pavlushkina L, Filatova T, Antonova E, Timofeeva E, Butvilovskaya V, Lysov Y, Zasedatelev A, Rubina A
Abstract
Background: In addition to allergen-specific IgE (sIgE), allergen-specific IgG4 (sIgG4) antibodies are also involved in the immune response resulting from an allergen exposure. The aim of our study was to analyze sIgE and sIgG4 patterns in the most common allergic disorders: bronchial asthma, upper airway disorders and atopic dermatitis.
Methods: In this study a screening analysis of blood serum samples from 673 patients aged from 6 months to 17 years with different allergic entities was performed on microarrays. sIgE and sIgG4 levels to the most common allergens were estimated.
Results: sIgE response to most pollen allergens is more strongly associated with respiratory diseases than with atopic dermatitis, while sIgE responses to cat and dog dander are more strongly associated with bronchial asthma than with atopic dermatitis and upper airway disorders such as rhinosinusitis and allergic rhinitis. A lower prevalence of sIgG4 to pollen allergens in cases of atopic dermatitis is observed compared with that in cases of asthma and upper airway disorders. Analyzing all the allergic disorders, one can see that sIgG4 response to inhalant allergens is strongly associated with sensitization to the corresponding allergen.
Conclusion: Allergen-specific IgE and IgG4 patterns that are relevant to concrete allergic diseases differ by sIgE and sIgG4 prevalences to defined allergens.
PMID: 30524646 [PubMed]
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Intake of a fermented plant product attenuates allergic symptoms without changing systemic immune responses in a mouse model of Japanese cedar pollinosis.
World Allergy Organ J. 2018;11(1):31
Authors: Fujimura T, Hori A, Torii H, Kishida S, Matsuura Y, Kawamoto S
Abstract
Background: Japanese cedar pollinosis (JCP) is one of the most prevalent allergies in Japan. Within the past few decades, many food factors have been demonstrated to suppress symptoms of pollinosis and mast cell degranulation directly or indirectly. Herein, we conducted a study to clarify the anti-allergic potency of a fermented plant product (FPP) in JCP model mice.
Methods: Mice were administered FPP, 10-fold-diluted FPP, or saline every day for 40 days by oral gavage and sensitized with major Japanese cedar pollen allergens (SBP). The numbers of sneezes were counted for 5 minutes after SBP nasal challenge. We analyzed the SBP-specific immunoglobulin titers, serum concentration of mast cell protease 1, and cytokine production from splenocytes stimulated with SBP.
Results: The numbers of sneezes by the mice administered FPP were significantly suppressed compared to those administered saline. The 10-fold-diluted FPP also suppressed the number of sneezes compared to saline, although not significantly. Serum level of mast cell protease 1 tended to be suppressed in FPP-consumed mice compared to those in saline-treated mice. The SBP-specific immunoglobulin titers and cytokine production were comparable among the groups.
Conclusions: Our results suggest that FPP intake could attenuate JCP symptoms without change of systemic immune responses.
PMID: 30524645 [PubMed]
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Omalizumab in the treatment of eosinophilic granulomatosis with polyangiitis (EGPA): single-center experience in 18 cases.
World Allergy Organ J. 2018;11(1):39
Authors: Celebi Sozener Z, Gorgulu B, Mungan D, Sin BA, Misirligil Z, Aydin O, Bavbek S
Abstract
Background: Data are limited regarding the effectiveness of omalizumab in patients with eosinophilic granulomatosis with polyangiitis (EGPA). Our aim was to evaluate the clinical and functional effectiveness of omalizumab in patients with EGPA in long-term follow-up.
Methods: This study was a retrospective chart review of patients with EGPA who were treated with omalizumab injections between May 2012 and April 2018. Once treatment with omalizumab was started, data were collected at various time points: baseline, the 16th week, 1st year, and annually until the last evaluation.
Results: Eighteen patients (16F/2M) with a mean age of 48.61 ± 11.94 years were included. Data were available for all patients for the first year, 12 patients for the second year, 10 patients for the third year, 8 patients for the fourth year and 5 patients for the fifth year. All patients were on mean dosage of 15.77 ± 7.6 mg/day oral corticosteroid (OCS) as daily bases for mean 8.61 ± 4 years besides high-dose inhaler corticosteroid/long-acting beta agonist. Antineutrophil cytoplasmic antibodies (ANCA) were positive in 2 patients, and 8 patients were diagnosed as having vasculitis by skin biopsy, one patient had polyneuropathy, and one patient had cardiac involvement.By considering the individual responses of patients and the level of improvement at the last evalulation, 10 (55.6%) patients responded completely, 1 responded partially, and 7 (38.9%) had no improvement. Omalizumab worked as a steroid-sparing agent in all patients and the daily OCS dose was reduced with a mean dosage of 6.28 mg/day at the end of the first year. The mean OCS reduction time for the whole group was 4 months. A reduction in asthma exacerbations/hospitalizations, improvement in forced expiratory volume in 1 second, and no decrease in the eosinophil count during treatment with omalizumab were also observed.
Conclusions: Omalizumab improved asthma control in some patients with EGPA with uncontrolled asthma by reducing asthma exacerbations and oral steroid requirement. However, more data are needed before recommending widespread use of omalizumab in patients with EGPA.
PMID: 30524647 [PubMed]
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Key mechanisms of cognitive behavioural therapy in irritable bowel syndrome: The importance of gastrointestinal related cognitions, behaviours and general anxiety.
J Psychosom Res. 2018 Nov 22;:
Authors: Windgassen S, Moss-Morris R, Goldsmith K, Chalder T
Abstract
BACKGROUND: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterised by abdominal pain and altered bowel movements. Cognitive behavioural therapy (CBT) has been shown to be effective in reducing symptom severity in IBS and enhancing quality of life/functioning. The present study sought to identify how CBT achieves change in these outcomes.
METHOD: Secondary analysis was conducted on 149 patients with irritable bowel syndrome who had been randomised to cognitive behavioural therapy plus an antispasmodic medication or antispasmodic alone. Single and sequential mediation was modelled using structural equation modelling. Gastrointestinal (GI) related avoidance behaviour, safety behaviour, cognitions and general anxiety were included as mediators.
RESULTS: GI safety behaviours, cognitions and general anxiety mediated treatment effect on the outcomes of symptom severity and work and social adjustment. Avoidance behaviour was not a significant mediator for either outcome. Sequential mediation models indicated that unhelpful GI related cognitions reduced before anxiety did, and this sequential path (R➔GI related cognitions➔anxiety➔outcome) was significant for both symptom severity (b = -0.22, CI [-0.40 to -0.90], p = .005) and work and social adjustment (b = -0.26, CI [-0.44 to -0.11], p = .003) where 'R' is randomisation. Reduction in GI safety behaviours also preceded reduction in anxiety. This sequence (R ➔GI safety behaviours➔anxiety➔outcome) was significant for both symptom severity (b = -0.11, CI [-0.24 to -0.01], p = .049) and work and social adjustment (b = -0.12, CI [-0.23 to -0.03], p = .03).
CONCLUSION: Results suggest that it is important for psychological treatments to target IBS specific factors for change.
PMID: 30522750 [PubMed - as supplied by publisher]
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Impact of Middle Turbinectomy on Airflow to the Olfactory Cleft: A Computational Fluid Dynamics Study.
Am J Rhinol Allergy. 2018 Dec 13;:1945892418816841
Authors: Alam S, Li C, Bradburn KH, Zhao K, Lee TS
Abstract
BACKGROUND: The impact of middle turbinate resection (MTR) on olfaction remains a point of debate in the current literature. Few studies have objectively evaluated olfactory cleft airflow following MTR; thus, the mechanism by which MTR may impact olfaction is poorly understood. It is not known whether the postsurgical changes in airway volume, flow, and resistance increase odorant transport or disrupt the patterns of normal airflow. Computational fluid dynamics can be used to study the nasal airway and predict responses to surgical intervention.
OBJECTIVE: To evaluate the functional impact of MTR on nasal airflow, resistance, and olfaction.
METHODS: Five maxillofacial computed tomography scans of patients without signs of significant sinusitis or nasal polyposis were used. Control models for each patient were compared to their corresponding model after virtual total MTR. For each model, nasal airway volume, nasal resistance, and air flow rate were determined. Odorant transport of 3 different odorants in the nasal cavity was simulated based on the computed steady airflow field.
RESULTS: Total airflow significantly increased following bilateral MTR in all patient models ( P < .05). Consistent with our airflow results, we found a decrease in nasal resistance following MTR. MTR significantly increased area averaged flux to the olfactory cleft when compared to controls for phenylethyl alcohol (high-sorptive odorant). Results for carvone (medium sorptive) were similarly elevated. MTR impact on limonene, a low flux odorant, was equivocal.
CONCLUSION: MTR increases nasal airflow while decreasing the nasal resistance. Overall, olfactory flux increased for high sorptive (phenylethyl alcohol) and medium sorpitve (l-carvone) odorants. However, the significant variation observed in one of our models suggests that the effects of MTR on the nasal airflow and the resultant olfaction can vary between individuals based on individual anatomic differences.
PMID: 30543120 [PubMed - as supplied by publisher]
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Evolution of symptoms and quality of life during Zika virus infection: A 1-year prospective cohort study.
J Clin Virol. 2018 Dec;109:57-62
Authors: de Laval F, d'Aubigny H, Mathéus S, Labrousse T, Ensargueix AL, Lorenzi EM, Le Flem FX, André N, Belleoud D, Leparc-Goffart I, Rousset D, Simon F, Briolant S
Abstract
BACKGROUND: Although the complications of Zika virus infection have been well described, the clinical pattern has not been reported in enough detail to differentiate this infection from those with other arboviroses, and no longitudinal study has yet been published on the persistence of symptoms and quality of life.
OBJECTIVES: were to describe bio-clinical pattern and quality of life during ZIKV infection, and their evolution.
STUDY DESIGN: We present a 1-year clinical follow-up of 49 people infected with Zika virus in French Guiana, for whom the diagnosis was confirmed by RT-PCR in serum or urine.
RESULTS: Fever was inconsistent (95% confidence interval (CI), 39-67). Exanthema (CI, 84-100) was maculopapular, with pruritus and conjunctivitis, variable over time and disappeared 12 days after the onset of symptoms (CI, 10-14). Joint pain (CI, 39-67) occurred mainly in the hands, wrists, knees and ankles and lasted for 10 days (CI, 7-13). Asthenia (CI, 61-85) scored low (3/10) but lasted for 19 days (CI, 16-22). The last two symptoms strongly limited patients' activities in the acute stage of the disease (RAPID-3 score, CI, 5-8). None of the patients had neurological complications, but 41% (CI, 27-55) had areflexia during the first month.
CONCLUSIONS: We found no real chronic evolution or decreased quality of life, function or ability to work from the first month after symptom onset.
PMID: 30523784 [PubMed - in process]
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Histopathology of human small intestinal and colonic ischemia-reperfusion: experiences from human IR-models.
Histol Histopathol. 2018 Dec 13;:18074
Authors: Leenarts CA, Grootjans J, Hundscheid IH, Schellekens DH, Lenaerts K, Buurman WA, Dejong CH, Derikx JP
Abstract
Intestinal ischemia-reperfusion (IR) injury is a frequent, but potentially life-threatening condition. Although much has been learned about its pathophysiology from animal IR models, the translation to the human setting is imperative for better understanding of its etiology. This could provide us with new insight into development of early detection and potential new therapeutic strategies. Over the past decade, we have studied the pathophysiology of human small intestinal and colonic ischemia-reperfusion (IR) in newly developed human in vivo IR models. In this review, we give an overview of new insights on the sequelae of human intestinal IR, with particular attention for the differences in histopathology between small intestinal and colonic IR.
PMID: 30543383 [PubMed - as supplied by publisher]
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Association Between High Neutrophil to Lymphocyte Ratio and Delayed Recovery From Bell's Palsy.
Clin Exp Otorhinolaryngol. 2018 Dec 15;:
Authors: Kim HS, Jung J, Dong SH, Kim SH, Jung SY, Yeo SG
Abstract
Objectives: Factors predictive of the severity of and recovery from Bell's palsy remain unclear. This study evaluated the association between neutrophil to lymphocyte ratio (NLR) and the severity of and recovery from Bell's palsy.
Methods: This retrospective study included 51 patients who were hospitalized with Bell's palsy from 2015 to 2017. Degree of paralysis was assessed by House-Brackmann (H-B) grade. Patients with H-B grades 2-4 were classified as having mild to moderate palsy and patients with H-B grade 5 or 6 were classified as having severe palsy. Patients were evaluated for obesity, hypertension and diabetes mellitus, and blood tests were performed to determine NLR and platelet to lymphocyte ratio. Patients were treated with steroids and antiviral agents. H-B grade was assessed 1 week, 1 month, and 3 months after treatment.
Results: NLR was significantly higher in patients with severe than with mild to moderate palsy (P=0.048). Recovery time was significantly longer in patients with high NLR than low NLR (P=0.045).
Conclusion: Higher NLR in patients with Bell's palsy was associated with longer recovery time. NLR may be prognostic of recovery time in patients with Bell's palsy.
PMID: 30545211 [PubMed - as supplied by publisher]
119 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
These pubmed results were generated on 2018/12/14
PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
| Related Articles |
Association Between High Neutrophil to Lymphocyte Ratio and Delayed Recovery From Bell's Palsy.
Clin Exp Otorhinolaryngol. 2018 Dec 15;:
Authors: Kim HS, Jung J, Dong SH, Kim SH, Jung SY, Yeo SG
Abstract
Objectives: Factors predictive of the severity of and recovery from Bell's palsy remain unclear. This study evaluated the association between neutrophil to lymphocyte ratio (NLR) and the severity of and recovery from Bell's palsy.
Methods: This retrospective study included 51 patients who were hospitalized with Bell's palsy from 2015 to 2017. Degree of paralysis was assessed by House-Brackmann (H-B) grade. Patients with H-B grades 2-4 were classified as having mild to moderate palsy and patients with H-B grade 5 or 6 were classified as having severe palsy. Patients were evaluated for obesity, hypertension and diabetes mellitus, and blood tests were performed to determine NLR and platelet to lymphocyte ratio. Patients were treated with steroids and antiviral agents. H-B grade was assessed 1 week, 1 month, and 3 months after treatment.
Results: NLR was significantly higher in patients with severe than with mild to moderate palsy (P=0.048). Recovery time was significantly longer in patients with high NLR than low NLR (P=0.045).
Conclusion: Higher NLR in patients with Bell's palsy was associated with longer recovery time. NLR may be prognostic of recovery time in patients with Bell's palsy.
PMID: 30545211 [PubMed - as supplied by publisher]
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SETDB1 regulates SMAD7 expression for breast cancer metastasis.
BMB Rep. 2018 Dec 14;:
Authors: Ryu TY, Kim K, Kim SK, Oh JH, Min JK, Jung CR, Son MY, Kim DS, Cho HS
Abstract
Breast cancer (BRC) is the most invasive cancer in women. Although the survival rate of BRC is gradually increasing due to improved screening systems, development of novel therapeutic targets for inhibition of BRC proliferation, metastasis and recurrence have been constantly needed. Thus, in this study, we identified overexpression of SETDB1 (SET Domain Bifurcated 1), a histone methyltransferase, in RNA-seq data of BRC derived from TCGA portal. In Gene Ontology (GO) analysis, cell migration-related GO terms were enriched, and we confirmed down-regulation of cell migration/invasion and alteration of EMT /MET markers after knockdown of SETDB1. Moreover, gene network analysis showed that SMAD7 expression is regulated by SETDB1 levels, indicating that up-regulation of SMAD7 by SETDB1 knockdown inhibited BRC metastasis. Therefore, development of SETDB1 inhibitors and functional studies may help develop more effective clinical guidelines for BRC treatment.
PMID: 30545440 [PubMed - as supplied by publisher]
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Tat-ATOX1 inhibits inflammatory responses via regulation of MAPK and NF-κB pathways.
BMB Rep. 2018 Dec 14;:
Authors: Kim DW, Shin MJ, Choi YJ, Kwon HJ, Lee SH, Lee S, Park J, Han KH, Eum WS, Choi SY
Abstract
Antioxidant 1 (ATOX1) protein has been reported to exhibit various protective functions, including antioxidant and chaperone. However, the effects of ATOX1 on the inflammatory response has not been fully elucidated. Thus, we prepared cell permeable Tat-ATOX1 and studied the effects on lipopolysaccharide (LPS)- and 12-O-tetradecanoyl phorbol-13- acetate (TPA)-induced inflammation. Experimental results showed that transduced Tat-ATOX1 protein significantly suppressed LPS-induced intracellular reactive oxygen species (ROS). Also, Tat-ATOX1 protein markedly inhibited LPS- and TPA-induced inflammatory responses by decreasing cyclooxygenase- 2 (COX-2) and inducible nitric oxide synthase (iNOS) and further inhibited phosphorylation of mitogen activated protein kinases (MAPKs; JNK, ERK and p38) and the nuclear factor-kappaB (NF-B) signaling pathway. These results indicate that the Tat-ATOX1 protein has a pivotal role in inflammation via inhibition of inflammatory responses, suggesting Tat-ATOX1 protein may offer a therapeutic strategy for inflammation.
PMID: 30545441 [PubMed - as supplied by publisher]
31 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
These pubmed results were generated on 2018/12/14
PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
| Related Articles |
Mitochondria and aging.
BMB Rep. 2018 Dec 14;:
Authors: Son JM, Lee C
Abstract
Aging is accompanied by a time-dependent progressive deterioration of multiple factors of the cellular system. The past several decades have witnessed major leaps in our understanding of the biological mechanism of aging using dietary, genetic, pharmacological, and physical interventions. Metabolic processes, including nutrient sensing pathways and mitochondrial function, have emerged as prominent regulators of aging. Mitochondria have been considered to play a key role largely due to their production of reactive oxygen species (ROS), resulting in DNA damage that accumulates over time and ultimately causes cellular failure. This theory, known as the mitochondrial free radical theory of aging (MFRTA), was favored by the aging field, but increasing inconsistent evidence has led to criticism and rejection of this idea. However, MFRTA should not be hastily rejected in its entirety because we now understand that ROS is not simply an undesired toxic metabolic byproduct, but also an important signaling molecule that is vital to cellular fitness. Notably, mitochondrial function, a term traditionally referred to bioenergetics and apoptosis, has since expanded considerably. It encompasses numerous other key biological processes, including the following: (i) complex metabolic processes, (ii) intracellular and endocrine signaling/communication, and (iii) immunity/inflammation. Here, we will discuss shortcomings of previous concepts regarding mitochondria in aging and their emerging roles based on recent advances. We will also discuss how the mitochondrial genome integrates with major theories on the evolution of aging.
PMID: 30545443 [PubMed - as supplied by publisher]
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An aortic calcification in a seventeenth-century autopsy report: The case of Cardinal Camillo Melzi.
Atherosclerosis. 2018 Nov 27;:
Authors: Riva MA, Belingheri M
PMID: 30522784 [PubMed - as supplied by publisher]
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Development and evaluation of a pan-dermatophyte PCR with species-level identification using sloppy molecular beacon probes.
Br J Dermatol. 2018 Dec 07;:
Authors: Walser M, Bosshard PP
Abstract
BACKGROUND: Conventional laboratory diagnosis of dermatophyte infection is cumbersome and time-consuming.
OBJECTIVES: We aimed to establish a simple, robust, and rapid molecular diagnostic assay for detection of dermatophytes and optionally non-dermatophytes in clinical specimens.
METHODS: We developed a two-tube pan-dermatophyte PCR assay using six sloppy molecular beacon (SMB) probes. The first PCR uses dermatophyte specific primers and enables detection and identification of most dermatophyte species. The second PCR with pan-fungal primers allows further differentiation of T. interdigitale and T. mentagrophytes/T. quinckeanum, T. violaceum and T. soudanense, and T. tonsurans and T. equinum, and detection of non-dermatophytes. The test was evaluated with 306 clinical specimens by comparing it to the results of microscopy and culture.
RESULTS: In melting curve analyses, species-specific Tm signatures of the SMBs were defined. Thus, our new PCR enabled detection and species-level identification of at least 19 dermatophyte species. Sensitivity and specificity of PCR for detection of dermatophytes in clinical samples were estimated to be 96.9% and 90.4%, for culture 46.7% and 98.7%, and for microscopy 91.4% and 84.0%, respectively. The detection of non-dermatophytes by PCR and culture did not correlate.
CONCLUSIONS: The new assay showed excellent performance characteristics for the detection of dermatophytes and is significantly faster than culturing techniques what makes it very promising for routine diagnostics of dermatophytosis. We noticed that the detection of non-dermatophytes in our assay currently has no benefit. This article is protected by copyright. All rights reserved.
PMID: 30525184 [PubMed - as supplied by publisher]
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Modulation of senoinflammation by calorie restriction based on biochemical and Omics big data analysis.
BMB Rep. 2018 Dec 14;:
Authors: Bang E, Lee B, Noh SG, Kim DH, Jung HJ, Ha S, Yu BP, Chung HY
Abstract
Aging is a complex and progressive process characterized by physiological and functional decline with time that increases susceptibility to diseases. Aged-related functional change is accompanied by a low-grade, unresolved chronic inflammation as a major underlying mechanism. In order to explain aging in the context of chronic inflammation, a new integrative concept on age-related chronic inflammation is necessary that encompasses much broader and wider characteristics of cells, tissues, organs, systems, and interactions between immune and non-immune cells, metabolic and non-metabolic organs. We have previously proposed a novel concept of senescent (seno)-inflammation and provided its frameworks. This review summarizes senoinflammation concept and additionally elaborates modulation of senoinflammation by calorie restriction (CR). Based on aging and CR studies and systems-biological analysis of Omics big data, we observed that senescence associated secretory phenotype (SASP) primarily composed of cytokines and chemokines was notably upregulated during aging whereas CR suppressed them. This result further strengthens the novel concept of senoinflammation in aging process. Collectively, such evidence of senoinflammation and modulatory role of CR provide insights into aging mechanism and potential interventions, thereby promoting healthy longevity.
PMID: 30545444 [PubMed - as supplied by publisher]
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Growth Signaling and Longevity in Mouse Models.
BMB Rep. 2018 Dec 14;:
Authors: Kim SS, Lee CK
Abstract
Reduction of insulin/insulin-like growth factor 1 (IGF1) signaling (IIS) extends the lifespan of various species. So far, several longevity mouse models have been developed containing mutations related to growth signaling deficiency by targeting growth hormone (GH), IGF1, IGF1 receptor, insulin receptor, and insulin receptor substrate. In addition, p70 ribosomal protein S6 kinase 1 (S6K1) knockout leads to lifespan extension. S6K1 encodes an important kinase in the regulation of cell growth. S6K1 is regulated by mechanistic target of rapamycin (mTOR) complex 1. The v-myc myelocytomatosis viral oncogene homolog (MYC)-deficient mice also exhibits a longevity phenotype. The gene expression profiles of these mice models have been measured to identify their longevity mechanisms. Here, we summarize our knowledge of long-lived mouse models related to growth and discuss phenotypic characteristics, including organ-specific gene expression patterns.
PMID: 30545442 [PubMed - as supplied by publisher]
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Disease model organism for Parkinson Disease: Drosophila melanogaster.
BMB Rep. 2018 Dec 14;:
Authors: Aryal B, Lee Y
Abstract
Parkinson's disease (PD) is a common neurodegenerative disorder characterized by selective and progressive loss of dopaminergic neurons. Genetic and environmental risk factors are associated with this disease. The genetic factors are composed of approximately 20 genes, such as SNCA, parkin, PTEN-induced kinase1 (pink1), leucine-rich repeat kinase 2 (LRRK2), ATP13A2, MAPT, VPS35, and DJ-1, whereas the environmental factors consist of oxidative stress-induced toxins such as 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP), rotenone, and paraquat. The analyses of their functions and mechanisms have provided important insights into the disease process, which has demonstrated that these factors cause oxidative damage and mitochondrial dysfunction. The most invaluable studies have been performed using disease model organisms, such as mice, fruit flies, and worms. Among them, Drosophila melanogaster has emerged as an excellent model organism to study both environmental and genetic factors and provide insights to the pathways relevant for PD pathogenesis, facilitating development of therapeutic strategies. In this review, we have focused on the fly model organism to summarize recent progress, including pathogenesis, neuroprotective compounds, and newer approaches.
PMID: 30545438 [PubMed - as supplied by publisher]
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UBE2S promotes the proliferation and survival of human lung adenocarcinoma cells.
BMB Rep. 2018 Dec 14;:
Authors: Liu Z, Xu L
Abstract
Ubiquitin-conjugating enzyme E2S (UBE2S), a family of E2 protein in the ubiquitination process, is involved in development of various cancers. However, its role in lung adenocarcinoma, has not been well elucidated. In this report, we attempted to investigate expression and function of UBE2S in lung adenocarcinoma. Up-regulation of UBE2S at mRNA, and protein level, was observed in human cancer tissues and lung adenocarcinoma cells. Higher UBE2S expression correlated with poorer prognosis of lung adenocarcinoma patients. UBE2S expression was efficiently suppressed by lentivirus-mediated shRNA strategy in A549 cells, and UBE2S silencing led to reduced cell proliferation, colony formation, and enhanced apoptosis. Inverse results were observed, in UBE2S over-expressed H1299 cells. Microarray analysis indicated that a large number of genes were regulated by UBE2S, and p53 signaling pathway may be critical, to the role of UBE2S in cancer development. Together, UBE2S could be a potential target for lung adenocarcinoma.
PMID: 30545437 [PubMed - as supplied by publisher]
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Phyllanthin and hypophyllanthin from Phyllanthus amarus ameliorates immune-inflammatory response in ovalbumin-induced asthma: role of IgE, Nrf2, iNOs, TNF-α, and IL's.
Immunopharmacol Immunotoxicol. 2018 Dec 12;:1-13
Authors: Wu W, Li Y, Jiao Z, Zhang L, Wang X, Qin R
Abstract
BACKGROUND: Asthma is a chronic airway immunoinflammatory disorder characterized by airway remodeling. Phyllanthus amarus has been reported to possess antioxidant and anti-inflammatory potential.
AIM: To evaluate the possible mechanism of action of isolated phytoconstituents from P. amarus (PA) against ovalbumin (OVA)-induced experimental airway hyperresponsiveness (AHR).
MATERIAL AND METHOD: Phyllanthin and hypophyllanthin were isolated and characterized (HPLC) from the methanolic extract of PA. AHR was induced in Sprague-Dawley rats by OVA-challenged, and animals were treated with PA (50, 100, and 200 mg/kg, p.o.) for 28 days.
RESULTS: The HPLC analysis showed the presence of phyllanthin and hypophyllanthin in methanolic extract of PA at RT of 25.243 and 26.832 min, respectively. OVA-induced alterations in hemodynamic parameters, lung functions test, peripheral blood oxygen level, total, and differential cell count in Bronchoalveolar Lavage Fluid was significantly attenuated (p < .05) by PA (100 and 200 mg/kg). It also significantly decreased (p < .05) the levels of total protein and albumin in serum, BALF, and lungs. OVA-induced increase in IgE (total and OVA-specific), and oxido-nitrosative stress (SOD, GSH, MDA, and NO) levels were significantly (p < .05) decreased by PA. RT-PCR analysis revealed that elevated oxido-nitrosative stress (Nrf2 and iNOs), immune-inflammatory makers (HO-1, TNF-α, IL-1β, and TGF-β1), Th2 cytokines (IL-4 and IL-6) levels were significantly attenuated (p < .05) by PA. PA also attenuated histological and ultrastructural aberrations induced by OVA.
CONCLUSION: Results of the present investigation demonstrated that the presence of phyllanthin and hypophyllanthin in P. amarus alleviated Th2 response in OVA-induced AHR via modulation of endogenous markers in a murine model of asthma. Thus, phyllanthin and hypophyllanthin may be a new therapeutic approach for the management of asthma.
PMID: 30541359 [PubMed - as supplied by publisher]
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Salvage or Solution: Alloplastic Reconstruction in Hemifacial Microsomia.
Cleft Palate Craniofac J. 2018 Dec 13;:1055665618817669
Authors: Polley JW, Girotto JA, Fahrenkopf MP, Dietze-Fiedler ML, Kelley JP, Taylor JC, Lazarou SA, Demetriades NC
Abstract
INTRODUCTION:: Skeletal reconstruction in severe grades of hemifacial microsomia (HFM) continues to be challenging. Traditional techniques of autografts and osseous distraction for reconstruction of the glenoid fossa, condyle, and ramus can fall short of expectations and can create new problems. This intercontinental study analyzes the role of alloplastic skeletal rehabilitation in severe HFM.
METHODS:: Ten consecutive patients with Pruzansky grade III HFM were reconstructed between October 2014 and July 2017 at 2 craniofacial centers following the same protocol. Data were gathered retrospectively from the medical records, including photographs and virtual planning records. Pre and postoperative photos were taken to compare occlusal status, interincisal opening, sagittal mandibular projection, and posterior facial height. Alloplastic reconstruction was accomplished using a custom designed titanium implant.
RESULTS:: Ten consecutive skeletally mature patients with HFM with failed traditional reconstructions were successfully treated with virtually planned alloplastic reconstructions (11 joints) and simultaneous orthognathic surgery. The glenoid fossa, condyle, and ramus on the affected sides were reconstructed with custom designed titanium implants. All patients achieved occlusal stabilization, normalization of posterior facial height and sagittal mandibular projection, and maintenance or improved inter-incisal opening. There were no major complications or repeated surgeries. Follow-up ranges from 6 to 50 months.
CONCLUSION:: Alloplastic reconstruction allows for precise vertical reconstruction of the ramus and condyle and sagittal repositioning of the mandibular body. The glenoid fossa component is firmly anchored to the skull base assuring a stable centric relation on the reconstructed side. Consistent and acceptable results can be achieved in skeletally mature patients.
PMID: 30543122 [PubMed - as supplied by publisher]
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Supporting general hospital staff to provide dementia sensitive care: A realist evaluation.
Int J Nurs Stud. 2018 Nov 30;:
Authors: Handley M, Bunn F, Goodman C
Abstract
BACKGROUND: There are an increasing number of interventions to improve hospital care for patients with dementia. Evidence for their impact on staff actions and patient outcomes is, however, limited and context dependent.
OBJECTIVE: To explain the factors that support hospital staff to provide dementia sensitive care and with what outcomes for patients with dementia.
DESIGN: A realist evaluation using a two-site case study approach.
SETTING: Two hospital trusts in the East of England. Site 1 had a ward for patients with dementia that would address their medical and mental health needs. Site 2 used a team of healthcare assistants, who had support from dementia specialist nurses, to work with patients with dementia across the hospital.
PARTICIPANTS: Hospital staff who had a responsibility for inpatients with dementia (healthcare assistants, nurses, medical staff, allied healthcare professionals and support staff) (n = 36), patients with dementia (n = 28), and family carers of patients with dementia (n = 2).
METHODS: A three stage realist evaluation: 1) building the programme theory of what works and when; 2) testing the programme theory through empirical data (80 h non-participant observation, 42 interviews, 28 patient medical notes, 27 neuropsychiatric inventory, and documentary review); 3) synthesis and verification of findings with key stakeholders.
FINDINGS: The programme theory comprised six interconnected context-mechanism-outcome configurations: 1) knowledge and authority to respond to an unmet need; 2) role relevant training and opportunities for reflection; 3) clinical experts and senior staff promoting practices that are patient-focused; 4) engaging with opportunities to spend time with patients; 5) risk management as an opportunity for person-centred care; 6) valuing dementia care as skilled work. Effective interactions reduced patient distress and supported patient orientation. Training and allocation of staff time were of themselves insufficient to ensure dementia care was prioritised and valued as skilled work. Staff concerns about the consequences of adverse incidents and work pressures on the ward, even with support, took precedence and influenced the quality of their interactions with patients with dementia. A key finding linked to staff retention and developing capacity in the workforce to provide expert dementia care was that despite extra training and organisational endorsement, nursing staff did not regard dementia care as skilled nursing work.
CONCLUSIONS: There is increased awareness and organisational commitment to dementia-friendly healthcare in general hospitals. However, in addition to training and adapting the environment to the patient, further work is needed to make explicit the specialist skills required for effective dementia care.
PMID: 30545567 [PubMed - as supplied by publisher]
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What information do patients want across their cancer journeys? A network analysis of cancer patients' information needs.
Cancer Med. 2018 Dec 07;:
Authors: Tran Y, Lamprell K, Nic Giolla Easpaig B, Arnolda G, Braithwaite J
Abstract
BACKGROUND: Patients want information across their cancer journeys. We investigated what sort of information they want and at what stage in the cancer journey by examining English patients' satisfaction derived from ratings of their care.
METHODS: Using patient experience data from 209 Clinical Commission Groups (CCGs) involving 72 788 respondents in 2016, overall patient satisfaction ratings and information needs questions were extracted. Novel network analysis techniques were used to construct an undirected weighted concentration network to assess the relationship between information needs and patient satisfaction.
RESULTS: From the network analysis, we found that patients value information early in the pathway; there were higher associations between patient satisfaction and when information needs are met in earlier phases of the cancer journey. Across the stages of the cancer journey, strong associations between information needs and patient satisfaction emerged during diagnostic testing and also at those points when patients received information provided by the clinical nurse specialists. A mixture of strong and weak associations between patient satisfaction and information needs was found during later phases of the cancer journey, specifically when patients move from treatment to home care. Our study identified that meeting needs for information related to supportive care may be a weaker factor in patient satisfaction than meeting needs for information related to the patient's disease, its treatment and the side effects of treatment.
CONCLUSION: If patients have their information needs met, especially during stages within the cancer journey when information needs are highest, they are more likely to be satisfied with their care. Our study has implications for information giving and improving patient satisfaction in cancer care.
PMID: 30525298 [PubMed - as supplied by publisher]
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Neuronal Constituents and Putative Interactions Within the Drosophila Ellipsoid Body Neuropil.
Front Neural Circuits. 2018;12:103
Authors: Omoto JJ, Nguyen BM, Kandimalla P, Lovick JK, Donlea JM, Hartenstein V
Abstract
The central complex (CX) is a midline-situated collection of neuropil compartments in the arthropod central brain, implicated in higher-order processes such as goal-directed navigation. Here, we provide a systematic genetic-neuroanatomical analysis of the ellipsoid body (EB), a compartment which represents a major afferent portal of the Drosophila CX. The neuropil volume of the EB, along with its prominent input compartment, called the bulb, is subdivided into precisely tessellated domains, distinguishable based on intensity of the global marker DN-cadherin. EB tangential elements (so-called ring neurons), most of which are derived from the DALv2 neuroblast lineage, predominantly interconnect the bulb and EB domains in a topographically organized fashion. Using the DN-cadherin domains as a framework, we first characterized this connectivity by Gal4 driver lines expressed in different DALv2 ring neuron (R-neuron) subclasses. We identified 11 subclasses, 6 of which correspond to previously described projection patterns, and 5 novel patterns. These subclasses both spatially (based on EB innervation pattern) and numerically (cell counts) summate to the total EB volume and R-neuron cell number, suggesting that our compilation of R-neuron subclasses approaches completion. EB columnar elements, as well as non-DALv2 derived extrinsic ring neurons (ExR-neurons), were also incorporated into this anatomical framework. Finally, we addressed the connectivity between R-neurons and their targets, using the anterograde trans-synaptic labeling method, trans-Tango. This study demonstrates putative interactions of R-neuron subclasses and reveals general principles of information flow within the EB network. Our work will facilitate the generation and testing of hypotheses regarding circuit interactions within the EB and the rest of the CX.
PMID: 30546298 [PubMed - in process]
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Early effects of eccentric contractions on muscle glucose uptake.
J Appl Physiol (1985). 2018 Dec 13;:
Authors: Andersen OE, Nielsen OB, Overgaard K
Abstract
Muscle damaging eccentric exercise impairs muscle glucose uptake several hours to days after exercise. Little, however, is known about the acute effects of eccentric exercise on contraction- and insulin-induced glucose uptake. This study compares glucose uptake rates in the first hours following eccentric, concentric, and isometric contractions with and without insulin present. Isolated rat extensor digitorum longus muscles were exposed to either an eccentric, concentric, or isometric contraction protocol, and muscle contractions were induced by electric stimulation that were identical between contraction protocols. In eccentric and concentric modes length changes of 0.6 or 1.2 mm were used during contractions. Both contraction- and insulin-induced glucose uptake were assessed immediately and two hours after contractions. Glucose uptake increased significantly following all modes of contraction and was higher after eccentric contractions with a stretch of 1.2 mm compared to the remaining contraction groups when assessed immediately after contractions (eccentric(1.2mm) > eccentric(0.6mm), concentric(1.2mm), concentric(0.6 mm), isometric > rest; P<0.05). After two hours, contraction-induced glucose uptake was still higher than non-contracting levels but with no difference between contraction modes. The presence of insulin increased glucose uptake markedly, but this response was blunted by respectively 39-51% and 29-36% (p < 0.05) immediately and two hours after eccentric contractions stretched 1.2 mm when compared to concentric and isometric contractions. The contrasting early effects of eccentric contractions on contraction- and insulin-induced glucose uptake suggests that glucose uptake is impaired acutely following eccentric exercise due to reduced insulin responsiveness.
PMID: 30543500 [PubMed - as supplied by publisher]
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A Pipeline for Volume Electron Microscopy of the Caenorhabditis elegans Nervous System.
Front Neural Circuits. 2018;12:94
Authors: Mulcahy B, Witvliet D, Holmyard D, Mitchell J, Chisholm AD, Samuel ADT, Zhen M
Abstract
The "connectome," a comprehensive wiring diagram of synaptic connectivity, is achieved through volume electron microscopy (vEM) analysis of an entire nervous system and all associated non-neuronal tissues. White et al. (1986) pioneered the fully manual reconstruction of a connectome using Caenorhabditis elegans. Recent advances in vEM allow mapping new C. elegans connectomes with increased throughput, and reduced subjectivity. Current vEM studies aim to not only fill the remaining gaps in the original connectome, but also address fundamental questions including how the connectome changes during development, the nature of individuality, sexual dimorphism, and how genetic and environmental factors regulate connectivity. Here we describe our current vEM pipeline and projected improvements for the study of the C. elegans nervous system and beyond.
PMID: 30524248 [PubMed - in process]
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A Descending Circuit Derived From the Superior Colliculus Modulates Vibrissal Movements.
Front Neural Circuits. 2018;12:100
Authors: Kaneshige M, Shibata KI, Matsubayashi J, Mitani A, Furuta T
Abstract
The superior colliculus (SC) is an essential structure for the control of eye movements. In rodents, the SC is also considered to play an important role in whisking behavior, in which animals actively move their vibrissae (mechanosensors) to gather tactile information about the space around them during exploration. We investigated how the SC contributes to vibrissal movement control. We found that when the SC was unilaterally lesioned, the resting position of the vibrissae shifted backward on the side contralateral to the lesion. The unilateral SC lesion also induced an increase in the whisking amplitude on the contralateral side. To explore the anatomical basis for SC involvement in vibrissal movement control, we then quantitatively evaluated axonal projections from the SC to the brainstem using neuronal labeling with a virus vector. Neurons of the SC mainly sent axons to the contralateral side in the lower brainstem. We found that the facial nucleus received input directly from the SC, and that the descending projections from the SC also reached the intermediate reticular formation and pre-Bötzinger complex, which are both considered to contain neural oscillators generating rhythmic movements of the vibrissae. Together, these results indicate the existence of a neural circuit in which the SC modulates vibrissal movements mainly on the contralateral side, via direct connections to motoneurons, and via indirect connections including the central pattern generators.
PMID: 30524249 [PubMed - in process]
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Toward Identifying the Systems-Level Primitives of Cortex by In-Circuit Testing.
Front Neural Circuits. 2018;12:104
Authors: Valiant LG
PMID: 30524250 [PubMed - in process]
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A Bayesian network meta-analysis of the efficacy of targeted therapies and chemotherapy for treatment of triple-negative breast cancer.
Cancer Med. 2018 Dec 07;:
Authors: Chen H, Lu W, Zhang Y, Zhu X, Zhou J, Chen Y
Abstract
Triple-negative breast cancer (TNBC) is a heterogeneous disease with poorer prognosis than other subtypes, yet effective therapies are still not available. We aimed to compare the efficacy of various targeted therapies with chemotherapy (CT) in TNBC patients using a network meta-analysis. A systematic literature search was performed in PubMed, EMBASE, and the Cochrane Library. A total of 27 randomized controlled trials (RCTs), involving 6924 TNBC patients, were included. Olaparib significantly improved PFS (0.43, 0.29-0.64) and ORR (2.57, 1.31-5.09) in comparison with CT. As for bevacizumab + CT, it showed a significant improvement of PFS (0.66, 0.55-0.80) and ORR (2.15, 1.16-4.05) compared with CT + placebo. It was also superior to CT alone in PFS (0.48, 0.35-0.65) and pCR (1.30, 1.13-1.49 for breast and axillary nodes and 1.26, 1.11-1.44 for breast). Other targeted agents like iniparib, sorafenib, cetuximab, and ipatasertib combined with CT showed significant superiority in PFS compared with CT alone, and the HRs were 0.75 (0.62-0.90), 0.44 (0.21-0.91), 0.67 (0.47-0.96), and 0.44 (0.24-0.81), respectively, while some other agents such as sunitinib and cetuximab had the lowest SUCRA in OS, PFS, or ORR without any benefits. In conclusion, our results indicated that the addition of bevacizumab to CT was beneficial for TNBC patients, and olaparib had a great effect in PFS and ORR, especially for those with BRCA mutations. When combined with CT, targeted agents including iniparib, sorafenib, cetuximab, and ipatasertib may have better efficacies for treating TNBC.
PMID: 30525293 [PubMed - as supplied by publisher]
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MicroRNA amplification and detection technologies: opportunities and challenges for point of care diagnostics.
Lab Invest. 2018 Dec 12;:
Authors: Dave VP, Ngo TA, Pernestig AK, Tilevik D, Kant K, Nguyen T, Wolff A, Bang DD
Abstract
The volume of point of care (POC) testing continues to grow steadily due to the increased availability of easy-to-use devices, thus making it possible to deliver less costly care closer to the patient site in a shorter time relative to the central laboratory services. A novel class of molecules called microRNAs have recently gained attention in healthcare management for their potential as biomarkers for human diseases. The increasing interest of miRNAs in clinical practice has led to an unmet need for assays that can rapidly and accurately measure miRNAs at the POC. However, the most widely used methods for analyzing miRNAs, including Northern blot-based platforms, in situ hybridization, reverse transcription qPCR, microarray, and next-generation sequencing, are still far from being used as ideal POC diagnostic tools, due to considerable time, expertize required for sample preparation, and in terms of miniaturizations making them suitable platforms for centralized labs. In this review, we highlight various existing and upcoming technologies for miRNA amplification and detection with a particular emphasis on the POC testing industries. The review summarizes different miRNA targets and signals amplification-based assays, from conventional methods to alternative technologies, such as isothermal amplification, paper-based, oligonucleotide-templated reaction, nanobead-based, electrochemical signaling- based, and microfluidic chip-based strategies. Based on critical analysis of these technologies, the possibilities and feasibilities for further development of POC testing for miRNA diagnostics are addressed and discussed.
PMID: 30542067 [PubMed - as supplied by publisher]
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Does Social Exclusion Alter Sensory and Pain Thresholds in Children and Adolescents with Functional Abdominal Pain? - Results from a Preliminary Study.
Pain Med. 2018 Dec 13;:
Authors: Gulewitsch MD, Jusyte A, Weimer K, Schönenberg M
Abstract
Objective: Functional abdominal pain (AP) is a prevalent issue in childhood and adolescence. The contribution of psychosocial factors in the development and maintenance of this health problem is rather unclear, and experimental studies about underlying mechanisms are lacking. This study investigates whether experimentally induced social exclusion decreases sensory and pain thresholds in children suffering from AP.
Subjects: Twenty children/adolescents with AP and 22 healthy controls.
Methods: Children/adolescents participated in the Cyberball paradigm, which affects an experience of social exclusion. Thermal sensory and pain thresholds were measured before and after Cyberball.
Results: Children/adolescents with AP showed a divergent reaction regarding their sensory threshold after social exclusion: The control group exhibited a tendency toward a decreased sensory threshold whereas the AP group remained stable. Concerning the pain threshold, no effect of social exclusion could be identified. The increase of both thresholds ("numbing") after Cyberball was positively correlated with symptoms of mental health issues.
Conclusions: This is the first study to investigate changes in sensory and pain thresholds following painful social interactions in a sample of children/adolescents with a chronic pain condition. Results suggest that AP and control children differ in their reaction of sensory thresholds, which might indicate an altered processing of social exclusion. Replication and further methodological improvements are needed.
PMID: 30544137 [PubMed - as supplied by publisher]
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Lamotrigine as a mood stabilizer: insights from the pre-clinical evidence.
Expert Opin Drug Discov. 2018 Dec 07;:1-12
Authors: Miranda AS, Miranda AS, Teixeira AL
Abstract
INTRODUCTION: Lamotrigine (LTG) is a well-established anticonvulsant that is also approved for the prevention of mood relapses in bipolar disorder. However, the mechanisms underlying LTG mood stabilizing effects remain unclear. Areas covered: Herein, the pre-clinical evidence concerning LTG's' mode of action in depression and mania is reviewed. Bottlenecks and future perspectives for this expanding and promising field are also discussed. Pre-clinical studies have indicated that neurotransmitter systems, especially serotoninergic, noradrenergic and glutamatergic, as well as non-neurotransmitter pathways such as inflammation and oxidative processes might play a role in LTG's antidepressant effects. The mechanisms underlying LTG's anti-manic properties remain to be fully explored, but the available pre-clinical evidence points out to the role of glutamatergic neurotransmission, possibly through AMPA-receptors. Expert opinion: A major limitation of current pre-clinical investigations is that there are no experimental models that recapitulate the complexity of bipolar disorder. Significant methodological differences concerning time and dose of LTG treatment, administration route, animal strains, and behavioral paradigms also hamper the reproducibility of the findings, leading to contradictory conclusions. Moreover, the role of other mechanisms (e.g. inositol phosphate and GSK3β pathways) implicated in the mode of action of different mood-stabilizers must also be consolidated with LTG.
PMID: 30523725 [PubMed - as supplied by publisher]
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TBX1 functions as a tumor suppressor in thyroid cancer through inhibiting the activities of PI3K/AKT and MAPK/ERK pathways.
Thyroid. 2018 Dec 13;:
Authors: Na W, Li Y, Wei J, Pu J, Liu R, Yang Q, Guan H, Shi B, Hou P, Ji M
Abstract
BACKGROUND: TBX1 is a member of the T-box family of transcription factors characterized by a conserved DNA binding domain termed T-box. TBX1 has been reported to be downregulated in mouse skin tumors, and negatively regulated tumor cell growth; however, its role and exact mechanism in human cancers including thyroid cancer remain totally unknown.
METHODS: Quantitative RT-PCR (qRT-PCR) and western blot assays were performed to evaluate the expression of investigated genes. Methylation-specific PCR (MSP) and pyrosequencing were used to analyze TBX1 promoter methylation. The biological functions of TBX1 in thyroid cancer cells were determine by a series of in vitro and in vivo experiments. Chromatin immunoprecipitation Sequencing (ChIP-Seq) and dual-luciferase reporter assays were used to identify its downstream targets.
RESULTS: We demonstrated that TBX1 was frequently downregulated by promoter methylation in both papillary thyroid cancers (PTCs) and thyroid cancer cell lines. Ectopic expression of TBX1 in thyroid cancer cells dramatically inhibited cell viability, colony formation and tumorigenic potential in nude mice, and induced cell cycle arrest and apoptosis through modulating a panel of cell cycle- and apoptosis-related genes. In addition, ectopic expression of TBX1 significantly decreased migration and invasion potential of thyroid cancer cells through inhibiting the process of epithelial-mesenchymal transition (EMT) and the expression of matrix metalloproteinases (MMPs). On the other hand, TBX1 knockdown markedly promoted thyroid cancer cell viability and invasiveness. Mechanistically, TBX1 exerted its tumor suppressor function in thyroid cancer cells through inhibiting phosphorylation of AKT at Ser473 and ERK via regulating its downstream targets such as RNF41, PARK2 and PHLPP2.
CONCLUSIONS: Our data show that TBX1 is frequently inactivated by promoter methylation, and functions as a potential tumor suppressor in thyroid cancer through inhibiting the activities of PI3K/AKT and MAPK/ERK signaling pathways.
PMID: 30543152 [PubMed - as supplied by publisher]
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DIFFERENCES IN MICRORNA EXPRESSION PROFILE BETWEEN VASTUS LATERALIS SAMPLES AND MYOTUBES IN COPD CACHEXIA.
J Appl Physiol (1985). 2018 Dec 13;:
Authors: Barreiro E, Sancho-Muñoz A, Puig-Vilanova E, Salazar-Degracia A, Pascual-Guardia S, Casadevall C, Gea J
Abstract
Quadriceps muscle weakness and wasting are common comorbidities in COPD. MicroRNA expression upregulation may favor muscle mass growth and differentiation. We hypothesized whether the profile of muscle-enriched microRNAs in cultured myotubes differs between COPD patients of a wide range of body composition and healthy controls and whether expression levels of those microRNAs from COPD and controls differ between in vivo and in vitro conditions. Twenty-nine COPD patients (n=15 with muscle wasting, FFMI 15 kg/m2 and n=14 with normal body composition, FFMI 18 kg/m2) and 10 healthy controls (FFMI, 19 kg/m2) were consecutively recruited. Biopsies from the vastus lateralis were obtained in all study subjects. A fragment of each biopsy was used to obtain primary cultures, in which muscle cells were first proliferated to be then differentiated into actual myotubes. In both sets of experiments (in vivo biopsies and in vitro myotubes) the following muscle-enriched microRNAs were analyzed using qRT-PCR: miR-1, miR-133, miR-206, miR-486, miR-29a, miR-27a, and miR-181a from all the study subjects. While the expression of miR-1, miR-206, miR-486, and miR-29a was upregulated in the muscle biopsies of COPD patients compared to those of healthy controls, levels of all the study microRNAs in the myotubes (primary cultured cells) did not significantly differ between COPD patients and the controls. We conclude from these findings that environmental factors (blood flow, muscle metabolism, inflammation) taking place in vivo (biopsies) in muscles may account for the differences observed in microRNA expression between COPD patients and controls. In the myotubes, however, the expression of the same microRNAs did not differ between the study subjects as such environmental factors were not present. These findings suggest that therapeutic strategies should rather target environmental factors in COPD muscle wasting as the profile of microRNA expression in myotubes was similar in patients to that observed in the healthy controls.
PMID: 30543501 [PubMed - as supplied by publisher]
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Delayed myonuclear addition, myofiber hypertrophy and increases in strength with high-frequency low-load blood flow restricted training to volitional failure.
J Appl Physiol (1985). 2018 Dec 13;:
Authors: Bjørnsen T, Wernbom M, Løvstad AT, Paulsen G, D'Souza RF, Cameron-Smith D, Flesche A, Hisdal J, Berntsen S, Raastad T
Abstract
PURPOSE: To investigate muscle hypertrophy, strength, myonuclear and satellite cell (SC) responses to high-frequency blood flow restricted resistance exercise (BFRRE).
METHODS: Thirteen individuals (24±2 years [mean ± SD], 9 males) completed two 5-day-blocks of 7 BFRRE sessions, separated by a 10-day rest period. Four sets of unilateral knee extensions to voluntary failure at 20% of 1RM were conducted with partial blood flow restriction (90-100 mmHg). Muscle samples obtained before-, during, 3- and 10 days after training were analyzed for muscle fiber area (MFA), myonuclei, SC, and mRNA and miRNA expression. Muscle size was measured by ultrasonography and magnetic resonance imaging, and strength with 1RM knee-extension.
RESULTS: With the first block of BFRRE, SC number increased in both fiber types (70-80%, p<0.05), while type I and II MFA decreased by 6±7% and 15±11% (p<0.05), respectively. With the second block of training, muscle size increased by 6-8%, while the number of SC (type I: 80±63%, type II 147±95%), myonuclei (type I: 30±24%, type II: 31±28%) and MFA (type I: 19±19%, type II: 11±19%) peaked 10 days after the second block of BFRRE, whereas strength peaked after 20 days of detraining (6±6%, p<0.05). Pax7- and p21 mRNA expression were elevated during the intervention, while myostatin, IGF1R, MyoD, myogenin, cyclinD1 and -D2 mRNA did not change until 3-10 days post intervention.
CONCLUSION: High frequency low-load BFRRE induced robust increases in SC, myonuclei and muscle size, but modest strength gains. Intriguingly, the responses were delayed and peaked 10-20 days after the training intervention, indicating overreaching.
PMID: 30543499 [PubMed - as supplied by publisher]
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Step Frequency Patterns of Elite Ultramarathon Runners during a 100-km Road Race.
J Appl Physiol (1985). 2018 Dec 13;:
Authors: Burns GT, Zendler JM, Zernicke RF
Abstract
Step frequency (SF) in running has received substantial interest from researchers, coaches, therapists, and runners. It has been widely studied in controlled settings, but no study has measured it continuously in elite-level competition. The current study used wrist-based accelerometers in consumer-grade watches to monitor SF and SF variability of competitors in the 2016 100-km World Championship road race. Using linear mixed-model regression, SF and SF variability were assessed across the race. The average SF (steps-per-minute) of competitors (n=20) was 182.0 spm (range: 155.4-203.1 spm). Race fluctuations in SF were only influenced by the speed the competitors were running, with faster speeds being associated with greater SF (5.6 spm/m*s^-1, p<0.001). SF did not otherwise change over the course of the race. SF was further linked to the runner's stature (-123.1 spm/m, p=0.01), but not significantly related to sex, weight, age, or years of experience. The SF Coefficient-of-Variation was inversely associated with running speed and distance covered, with runners demonstrating decreasing variability at both faster speeds and as the race progressed. Together, these results add ecological evidence to observations of a speed-dependency of SF in a highly trained, elite population of runners and suggest that in road race conditions, SF changes only with speed and not fatigue. Furthermore, it presents evidence that the variability of an elite runner's SF is linked to both speed and fatigue, but not any other characteristics of the runner. The current findings are important for runners, clinicians, and coaches as they seek to monitor or manipulate SF.
PMID: 30543498 [PubMed - as supplied by publisher]
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Molecular subtype not immune response drives outcomes in endometrial carcinoma.
Clin Cancer Res. 2018 Dec 06;:
Authors: Talhouk A, Derocher H, Schmidt P, Leung S, Milne K, Gilks B, Anglesio MS, Nelson BH, McAlpine JN
Abstract
PURPOSE: Tumors with high mutation load are thought to engender stronger immune responses which in turn promote prolonged patient survival. To investigate this, we assessed tumor-infiltrating lymphocytes (TIL) and immunosuppressive factors across the four molecular subtypes of endometrial cancer (EC), which have characteristic mutation rates ranging from low to ultra-high.
EXPERIMENTAL DESIGN: 460 ECs were stratified by ProMisE (Proactive Molecular Risk Classifier in Endometrial cancer) into four molecular subtypes: mismatch repair-deficient (MMRd), POLE mutant (POLE), p53 abnormal (p53abn), and p53 wildtype (p53wt). Immune markers (CD3, CD8, CD79a, CD138, PD-1, PD-L1, FoxP3, IDO-1) were quantified by multiplex immunohistochemistry and tested for associations with ProMisE subtype, survival, and other clinicopathological parameters.
RESULTS: Two major TIL patterns were observed. TIL high tumors harbored dense T- and B-lineage infiltrates and multiple immunosuppressive features and were common in molecular subtypes associated with high mutation load (MMRd and POLE); however, equally strong responses were seen in significant numbers of p53abn and p53wt tumors, which have characteristically low mutation loads. TIL low tumors were generally devoid of immunological features and more prevalent in p53abn and p53wt ECs, yet were also seen in MMRd and POLE subtypes. In multivariable models involving ProMisE subtype, T-cell markers, TIL clusters, only ProMisE showed independent prognostic significance.
CONCLUSIONS: Immune response correlates with EC molecular subtype but does not carry independent prognostic significance. Profound variation in immune response is seen across and within EC molecular subtypes, suggesting that assessment of immune response rather than molecular subtype may better predict response to immunotherapy.
PMID: 30523022 [PubMed - as supplied by publisher]
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The Incidence of Meningitis in Patients with Traumatic Brain Injury Undergoing External Ventricular Drain Placement: A Nationwide Inpatient Sample Analysis.
Neurocrit Care. 2018 Dec 06;:
Authors: Hoffman H, Jalal MS, Chin LS
Abstract
BACKGROUND/OBJECTIVE: Infection is the most common complication of external ventricular drain (EVD) placement. National trends in the annual incidence of meningitis among patients with traumatic brain injury (TBI) who have undergone EVD placement have not been reported.
METHODS: The Nationwide Inpatient Sample was used to select adults with a primary diagnosis of TBI who underwent EVD placement between 2002 and 2011. Annual rates of meningitis among patients who underwent EVD placement were determined. We also calculated mortality rates and length of stay (LOS). Potential factors associated with meningitis were evaluated in a binary logistic regression analysis.
RESULTS: Out of 1,571,927 adult discharges with a primary diagnosis of TBI between 2002 and 2011, 39,029 (2.5%) underwent EVD placement. Of these, 1544 (4.3%) patients developed meningitis. There was no significant trend in the annual incidence of meningitis (p = 0.88), mortality (p = 0.55), or mean LOS (p = 0.13) during the study period. Meningitis and mortality rates remained stable when stratifying patients by hospital volume. In the binary logistic regression, acquired immunodeficiency syndrome, sepsis, and cerebrospinal fluid leak were associated with meningitis.
CONCLUSIONS: The incidence of meningitis in patients who underwent EVD placement remained stable between 2002 and 2011. Further prospective studies are needed to identify approaches for preventing these infections.
PMID: 30523540 [PubMed - as supplied by publisher]
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Desmoplastic Small Round Cell Tumors With Atypical Presentations: A Report of 34 Cases.
Int J Surg Pathol. 2018 Dec 06;:1066896918817140
Authors: Al-Ibraheemi A, Broehm C, Tanas MR, Horvai AE, Rubin BP, Cheah AL, Thway K, Fisher C, Bahrami A, Folpe AL, Fritchie KJ
Abstract
OBJECTIVES: Desmoplastic small round cell tumor (DSRCT) is an aggressive round cell sarcoma that arises in the abdominal cavity/pelvis of young males. We sought to expand its clinicopathologic spectrum.
METHODS: Cases of DSRCT presenting in patients >30 years of age or tumors arising outside of the abdominal cavity/pelvis were retrieved.
RESULTS: Thirty-four cases were identified. Sixteen tumors arose at atypical sites (head/neck, intracranial, thigh, axilla/shoulder, inguinal/paratesticular, intraosseous, and uterine corpus). The remaining 18 patients were older than 30 years, and their tumors involved the abdomen or pelvis. The majority of cases showed areas with classic histology, while 6 cases exhibited solid growth and 5 showed macronodular architecture. Cytologic appearance included round cell, rhabdoid, epithelioid, and small cell.
CONCLUSION: DSRCT may arise at nonabdominal locations in both pediatric and adult populations, as well as intra-abdominally in older adults, and these tumors exhibit high rates of metastasis and morbidity.
PMID: 30522375 [PubMed - as supplied by publisher]
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Mucosal Schwann Cell Hamartoma of the Rectosigmoid Junction: A Rare Lesion Mimicking Mucosal Prolapse Syndrome and Other Neural Lesions.
Int J Surg Pathol. 2018 Dec 12;:1066896918818897
Authors: Hashimoto H, Usui G, Sakai E, Ohata K, Morikawa T
Abstract
In this article, we report the case of a 40-year-old woman with a sessile polyp of the rectosigmoid junction that underwent endoscopic resection. The resected specimen showed spindle cell proliferation with eosinophilic cytoplasm between mucosal crypts, mimicking mucosal prolapse syndrome. However, these were immunohistochemically positive for S-100, indicating neural cell origin. As neural polypoid lesion of the rectum, neurofibroma, perineurioma, schwannoma, and mucosal Schwann cell hamartoma were in the differential diagnosis. Histology and additional immunohistochemistry confirmed mucosal Schwann cell hamartoma. Mucosal Schwann cell hamartoma of the rectosigmoid junction or rectum can be a histological mimic of mucosal prolapse syndrome and other S-100 positive neural cell lesions; however, the lesion in the present case was correctly diagnosed with histology and immunohistochemistry.
PMID: 30541360 [PubMed - as supplied by publisher]
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SLE dacryoadenitis.
Orbit. 2018 Dec 12;:1-4
Authors: Hung YC, Wang DD, Han LSM, Betts TD, Weatherhead RG
Abstract
In systemic lupus erythematosus, ophthalmic manifestations are noted in up to one-third of patients. We describe a patient with an unusual initial presentation of this disorder.
PMID: 30541377 [PubMed - as supplied by publisher]
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Sub-castrate testosterone nadir and clinical outcomes in intermediate or high-risk localized prostate cancer.
Int J Radiat Oncol Biol Phys. 2018 Dec 10;:
Authors: Bryant AK, McKay RR, Kader AK, Parsons JK, Einck JP, Kane CJ, Mundt AJ, Murphy JD, Rose BS
Abstract
PURPOSE: It is unclear if additional serum testosterone suppression below the castrate threshold of 50 ng/dL improves clinical outcomes in patients with localized prostate cancer (PCa) undergoing definitive therapy.
METHODS: We examined the association of sub-castrate testosterone nadir with PSA response and long-term clinical outcomes in 764 US veterans with intermediate- or high-risk localized PCa treated with ADT and definitive radiotherapy from 2000-2015. Patients were categorized into testosterone nadir groups based on the minimum testosterone measurement during continuous gonadotropic-releasing hormone agonist therapy (<20 ng/dL vs. 20-49 ng/dL). Outcomes included PSA response (3-month post-radiotherapy PSA and 2-year PSA nadir; multivariable linear regression) and long-term clinical outcomes (biochemical recurrence, metastasis, and PCa-specific mortality; Fine-Gray competing risk regression).
RESULTS: A testosterone nadir of 20-49 ng/dL was associated with higher 3-month post-radiotherapy PSA compared to <20 ng/dL (ß = 0.16, 95% CI 0.06-0.26, p=0.001) and higher 2-year PSA nadir (ß = 0.12, 95% CI 0.04-0.21, p=0.005). Compared to the <20 ng/dL group, the 20-49 ng/dL group showed higher 10-year biochemical recurrence rates (28.1% vs. 18.3%) and metastasis rates (12.9% vs. 7.8%) persisting on multivariable analyses (biochemical recurrence: subdistribution hazard ratio [SDHR] 1.62 for 20-49 ng/dL, 95% CI 1.07-2.45, p=0.02; metastasis: SDHR 2.19, 95% CI 1.21-3.94, p=0.009). There was a trend toward inferior PCa-specific mortality for the 20-49 ng/dL group (SDHR 1.95, 95% CI 0.90-4.22, p=0.09).
CONCLUSIONS: Additional serum testosterone suppression below 50 ng/dL was associated with improved PSA responses and lower rates of biochemical recurrence and metastasis in this cohort of localized PCa patients.
PMID: 30543857 [PubMed - as supplied by publisher]
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Calcium intake and survival after colorectal cancer diagnosis.
Clin Cancer Res. 2018 Dec 13;:
Authors: Yang W, Ma Y, Smith-Warner SA, Song M, Wu K, Wang M, Chan AT, Ogino S, Fuchs CS, Poylin V, Ng K, Meyerhardt JA, Giovannucci EL, Zhang X
Abstract
PURPOSE: Although evidence suggests an inverse association between calcium intake and colorectal cancer incidence, the influence of calcium on survival after colorectal cancer diagnosis remains unclear.
EXPERIMENTAL DESIGN: We prospectively assessed the association of postdiagnostic calcium intake with colorectal cancer-specific and overall mortality among 1,660 non-metastatic colorectal cancer patients within the Nurses' Health Study and the Health Professionals Follow-up Study. Patients completed a validated food frequency questionnaire between 6 months and 4 years after diagnosis and were followed up for death. Multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated using Cox proportional hazards regression.
RESULTS: Comparing the highest to the lowest quartile intake of postdiagnostic total calcium, the multivariable HRs were 0.56 (95% CI, 0.32 to 0.96, P trend = 0.04) for colorectal cancer-specific mortality and 0.80 (95% CI, 0.59 to 1.09, P trend = 0.11) for all-cause mortality. Postdiagnostic supplemental calcium intake was also inversely associated with CRC-specific mortality (HR = 0.67; 95% CI, 0.42 to 1.06; P trend = 0.047) and all-cause mortality (HR = 0.71; 95% CI, 0.54 to 0.94; P trend = 0.008), although these inverse associations were primarily observed in women. In addition, calcium from diet or dairy sources was associated with lower risk in men.
CONCLUSIONS: Higher calcium intake after the diagnosis may be associated with a lower risk of death among patients with colorectal cancer. If confirmed, these findings may provide support for the nutritional recommendations of maintaining sufficient calcium intake among colorectal cancer.
PMID: 30545821 [PubMed - as supplied by publisher]
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Keratinocyte Carcinomas: Current concepts and future research priorities.
Clin Cancer Res. 2018 Dec 06;:
Authors: Nagarajan P, Asgari MM, Green AC, Guhan SM, Arron ST, Proby CM, Rollison DE, Harwood CA, Toland AE
Abstract
Cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) are keratinocyte carcinomas (KC), the most frequently diagnosed cancers in fair-skinned populations. Ultraviolet radiation (UVR) is the main driving carcinogen for these tumors but immunosuppression, pigmentary factors, and aging are also risk factors. Scientific discoveries have improved the understanding of the role of human papillomaviruses (HPV) in cSCC as well as the skin microbiome and a compromised immune system in the development of both cSCC and BCC. Genomic analyses have uncovered genetic risk variants, high-risk susceptibility genes, and somatic events that underlie common pathways important in KC tumorigenesis and tumor characteristics which have enabled development of prediction models for early identification of high-risk individuals. Advances in chemoprevention in high-risk individuals and progress in targeted and immune-based treatment approaches have the potential to decrease the morbidity and mortality associated with these tumors. As the incidence and prevalence of KC continue to increase, strategies for prevention, including effective sun protective behavior, educational interventions and reduction of tanning bed access and usage are essential. Gaps in our knowledge requiring additional research in order to reduce the high morbidity and costs associated with KC include better understanding of factors leading to more aggressive tumors, the roles of microbiome and HPV infection, prediction of response to therapies including immune checkpoint blockade, and how to tailor both prevention and treatment to individual risk factors and needs.
PMID: 30523023 [PubMed - as supplied by publisher]
