Medicine by Alexandros G. Sfakianakis: 04/18/19

Thursday, April 18, 2019

Intraductal Carcinoma of the Prostate in the Absence of HighGrade Invasive Carcinoma Represents a Molecularly Distinct Type ofin situ Carcinoma Enriched with Oncogenic Driver Mutations

Intraductal Carcinoma of the Prostate in the Absence of High
Grade Invasive Carcinoma Represents a Molecularly Distinct Type of
in situ Carcinoma Enriched with Oncogenic Driver Mutations:

ABSTRACT

Intraductal
carcinoma of the prostate (IDC‐P) most often appears associated
with high grade invasive prostate carcinoma (PCa), where it is
believed to represent retrograde spread. However, IDC‐P rarely
occurs as an isolated finding at radical prostatectomy or with
concurrent low grade (Grade Group 1) invasive carcinoma. We
hypothesized that isolated IDC‐P (iIDC‐P) in these unusual cases
may represent a distinct in situ lesion and
molecularly profiled 15 cases. iIDC‐P was characterized by copy
number alteration profiling and targeted next generation sequencing
in cases with sufficient tissue (N=7). Immunohistochemistry for
PTEN and ERG were performed on the total cohort (N=15), where areas
of iIDC‐P and associated invasive disease were evaluated separately
(N=9). By copy number profiling, iIDC‐P alterations were similar to
those previously described in high grade invasive PCa
(PTEN, RB1, and
CHD1 loss; MYC gain).
However, in four cases, targeted sequencing revealed a striking
number of activating oncogenic driver mutations in MAPK and PI3K
pathway genes, which are extraordinarily rare in conventional PCa.
In addition, pathogenic mutations in DNA repair genes were found in
two cases of iIDC‐P (BRCA2, CHEK2,
CDK12) and other known PCa‐associated mutations
(FOXA1, SPOP) in two cases. Overall, ERG was
expressed in 7% (1/15) of the iIDC‐P lesions and PTEN was lost in
53% (8/15). Discordance for ERG or PTEN status between IDC‐P and
the low grade PCa was observed in five of nine cases, with intact
PTEN in the invasive tumor and PTEN loss in IDC‐P in four. Despite
a copy number alteration profile similar to conventional PCa,
iIDC‐P is enriched with potentially targetable oncogenic driver
mutations in MAPK/PI3K genes. Based on PTEN and ERG status, iIDC‐P
is not likely a precursor to the associated low grade invasive PCa,
but represents a molecularly unique in situ
tumor of unclear clinical significance.

Role of P53, E-cadherin and BRAF as predictors of regional nodal recurrence for papillary thyroid cancer

Role of P53, E-cadherin and BRAF as predictors of regional nodal recurrence for papillary thyroid cancer:

Publication date: Available online 16 April 2019

Source: Annals of Diagnostic Pathology

Author(s): Khadiga M. Ali, Shadi Awny, Dina Abdallah Ibrahim, Islam H. Metwally, Omar Hamdy, Basel Refky, Ahmed Abdallah, Khaled Abdelwahab

Abstract

Background

Regional nodal recurrence (RNR) in patients diagnosed with papillary thyroid carcinoma (PTC) has increased. Variable immunohistochemical (IHC) markers have been studied for predicting the likelihood of PTC for recurrence. We aimed to clarify the IHC expression of p53, Ecadherin and BRAF as potential markers of RNR in PTC.

Method

145 (73 study group and 72 control group) patients with PTC were analyzed retrospectively between January 2010 and June 2017. Further classification to a specific histological variant was done, and IHC expression of p53, Ecadherin and BRAF was analyzed both in the primary tumor and in nodal recurrence.

Results

Regarding the risk of RNR, we found certain clinicopathologic features as elder age ≥55 years, tumor size >1 cm, presence of microscopic extrathyroid extension, presence of lymphovascular emboli, and conventional papillary subtype. Furthermore, IHC results for negative E-cadherin, and positive P53 and BRAF are significant risk factors, while radioactive iodine (RAI) adjuvant therapy decrease recurrence risk.

Conclusion

We found several risk factors for RNR in PTC diagnosed patients, all of which are easily achievable in clinical settings. In this regard, we suggested that patients with specific clinicopathologic and immunohistochemical features have strict follow up for early detection of RNR as it has a great impact on their survival.

Localization of phospholipase C β3 in the major salivary glands of adult mice

Localization of phospholipase C β3 in the major salivary glands of adult mice:

Publication date: Available online 17 April 2019

Source: Acta Histochemica

Author(s): Atsara Rawangwong, Atthapon Pidsaya, Wipawee Thoungseabyoun, Apussara Tachow, Tarinee Sawatpanich, Waraporn Sakaew, Miwako Yamasaki, Masahiko Watanabe, Hisatake Kondo, Wiphawi Hipkaeo

Abstract

Phospholipase C (PLC)β has a role in saliva secretion by controlling intracellular Ca²⁺via its product, IP₃. The present study was attempted to localize PLCβ isoforms in mouse salivary glands in situ. A single major band was detected for PLCβ3 in immunoblots of the parotid and sublingual glands (PG, SLG), while no such band was seen in the submandibular gland (SMG). No bands were detected for PLCβ1 or 4 in the three glands. In immuno-light microscopy of PG and SLG, substantial immunoreactivity for PLCβ3 was seen in the cytoplasm including the plasmalemma of almost all ductal cells, while no distinct immunoreactivity was discerned in most acinar cells except for sublingual demilune cells. Numerous ductal cells exhibited higher immunoreactivity for PLCβ3 in their apical/supranuclear cell domain including the plasmalemma than in the basal/infranuclear domain, indicating an apico-basal polarity. In immuno-gold electron microscopy of PG ducts and SLG ducts and demilunes, most gold particles were found in association with plasma membranes as well as various intracellular membranes, most of which formed small oblong or flattened vesicles and vacuoles. A few particles were seen without association with any membranous structures. The present finding supports the previous physio-pharmacological result that Ca²⁺-signaling proteins as well as initial intracellular Ca²⁺ changes occur in the apical cell domain including the plasma membranes of the exocrine cells.

Habitat use and vestibular system's dimensions in lacertidlizards

Habitat use and vestibular system's dimensions in lacertid
lizards:

Abstract

The vestibular
system is crucial for movement control during locomotion. As the
dimensions of the vestibular system determine the fluid dynamics of
the endolymph and, as such, the system's function, we investigate
the interaction between vestibular system size, head size and
microhabitat use in lizards. We grouped 24 lacertid species in
three microhabitat types, we acquired three‐dimensional models of
the bony vestibular systems using micro‐computer tomography
scanning, and we performed linear and surface measurements. All
vestibular measurements scale with a negative allometry with head
size, suggesting that smaller heads house disproportionally large
ears. As the sensitivity of the vestibular system is positively
related to size, a sufficiently large vestibular system in
small‐headed animals may meet the sensitivity demands during
challenged locomotion. We also found that the microhabitat affects
the locomotor dynamics: lizards inhabiting open microhabitats run
at higher dimensionless speeds. On the other hand, no statistical
relationship exists between dimensionless speed and the vestibular
system dimensions. Hence, if the vestibular size would differ
between microhabitats, this would be a direct effect (i.e. imposed,
for instance, by requirements for manoeuvring, balance control,
etc.), rather than depending on the lizards’ intrinsic running
speed. However, we found no effect of the microhabitat on the
allometric relationship between head and vestibular system size.
The finding that microhabitat is not reflected in the vestibular
system size (hence sensitivity) of the lacertids in this study is
possibly due to spatial constraints of the
skull.

Fabella prevalence rate increases over 150 years, andrates of other sesamoid bones remain constant: a systematicreview

Fabella prevalence rate increases over 150 years, and
rates of other sesamoid bones remain constant: a systematic
review:

Abstract

The fabella
is a sesamoid bone located behind the lateral femoral condyle. It
is common in non‐human mammals, but the prevalence rates in humans
vary from 3 to 87%. Here, we calculate the prevalence of the
fabella in a Korean population and investigate possible temporal
shifts in prevalence rate. A total of 52.83% of our individuals and
44.34% of our knees had fabellae detectable by computed tomography
scanning. Men and women were equally likely to have a fabella, and
bilateral cases (67.86%) were more common than unilateral ones
(32.14%). Fabella presence was not correlated with height or age,
although our sample did not include skeletally immature
individuals. Our systematic review yielded 58 studies on fabella
prevalence rate from 1875–2018 which met our inclusion criteria,
one of which was an outlier. Intriguingly, a Bayesian mixed effects
generalized linear model revealed a temporal shift in prevalence
rates, with the median prevalence rate in 2000 (31.00%) being
~ 3.5 times higher than that in 1900 (7.64%). In all four
countries with studies before and after 1960, higher rates were
always found after 1960. Using data from two other systematic
reviews, we found no increase in prevalence rates of 10 other
sesamoid bones in the human body, indicating that the increase in
fabella prevalence rate is unique. Fabella presence/absence is due
to a combination of genetic and environmental factors: as the
prevalence rates of other sesamoid bones have not changed in the
last 100 years, we postulate the increase in fabella
prevalence rate is due to an environmental factor. Namely, the
global increase in human height and weight (due to improved
nutrition) may have increased human tibial length and muscle mass.
Increases in tibial length could lead to a larger moment arm acting
on the knee and on the tendons crossing it. Coupled with the
increased force from a larger gastrocnemius, this could produce the
mechanical stimuli necessary to initiate fabella formation and/or
ossification.

The sandwich structure of keratinous layers controls theform and growth orientation of chicken rhinotheca

The sandwich structure of keratinous layers controls the
form and growth orientation of chicken rhinotheca:

Abstract

The upper
beak bone of birds is known to be overlain by the rhinotheca, which
is composed of the horny sheath of keratinous layers. However, the
details of the structure and growth pattern of the rhinotheca are
yet to be understood. In this study, the microstructure of the
rhinotheca from chicken specimens of different growth stages
(ranging from 1 to ~ 80 days old) was analyzed using a
combination of thin section and scanning electron microscopy
observations, and small‐angle X‐ray scattering analysis. We found
that the rhinotheca comprises three different layers – outer,
intermediate, and inner layers – throughout its growth. The outer
layer arises from the proximal portion of the beak bone and covers
the dorsal surface of the rhinotheca, whereas the intermediate and
inner layers originate in the distal portion of the beak bone and
underlie the outer layer. This tri‐layered structure of the
rhinotheca was also observed in wild bird specimens (grey wagtail,
king quail, and brown dipper). On the median plane, micro‐layers
making up the outer and inner layers are bedded nearly parallel to
the rostral bone at the base. However, more distally positioned
micro‐layers of the outer layer are more anteverted distally. The
micro‐layers of the intermediate layer are bedded nearly
perpendicular to those of the outer and inner layers on the median
plane. The growth of micro‐layers in the intermediate layer adds
thickness to the rhinotheca, which causes the difference in profile
between the beak bone and the rhinotheca in the distal portion of
the beak. Moreover, the entire intermediate layer grows distally as
new proximal micro‐layers form. The outer layer is dragged distally
by the intermediate layer as a result of its distal growth, for the
three layers are closely packed to each other at their boundaries.
Furthermore, the occurrence of the intermediate and inner layers in
the distal portion of the rostral bone may be because the distal
end of the beak is frequently used and worn, and the rhinotheca
therefore needs to be replaced more frequently at the distal end.
The rhinotheca structure described here will be an important and
useful factor in the reconstruction of the beaks of birds in
extinct taxa.

Scaling of cardiac morphology is interrupted by birth in thedeveloping sheep Ovis aries

Scaling of cardiac morphology is interrupted by birth in the
developing sheep Ovis aries:

Abstract

Scaling of
the heart across development can reveal the degree to which
variation in cardiac morphology depends on body mass. In this
study, we assessed the scaling of heart mass, left and right
ventricular masses, and ventricular mass ratio, as a function of
eviscerated body mass across fetal and postnatal development in
Horro sheep Ovis aries (~50‐fold body mass
range; N = 21). Whole hearts were extracted from
carcasses, cleaned, dissected into chambers and weighed. We found a
biphasic relationship when heart mass was scaled against body mass,
with a conspicuous ‘breakpoint’ around the time of birth, manifest
not by a change in the scaling exponent (slope), but rather a jump
in the elevation. Fetal heart mass (g) increased with eviscerated
body mass (M_b, kg)
according to the power
equation 4.90 M_b^{0.88 ± 0.26

(± 95%}^CI⁾, whereas
postnatal heart mass increased according to
10.0 M_b^{0.88 ± 0.10}.
While the fetal and postnatal scaling exponents are identical
(0.88) and reveal a clear dependence of heart mass on body mass,
only the postnatal exponent is significantly less than 1.0,
indicating the postnatal heart becomes a smaller component of body
mass as the body grows, which is a pattern found frequently with
postnatal cardiac development among mammals. The rapid doubling in
heart mass around the time of birth is independent of any increase
in body mass and is consistent with the normalization of wall
stress in response to abrupt changes in volume loading and pressure
loading at parturition. We discuss variation in scaling patterns of
heart mass across development among mammals, and suggest that the
variation results from a complex interplay between hard‐wired
genetics and epigenetic influences.

Expression of Prox1 in Medullary Thyroid Carcinoma Is Associated with Chromogranin A and Calcitonin Expression and with Ki67 Proliferative Index, but Not with Prognosis

Expression of Prox1 in Medullary Thyroid Carcinoma Is Associated with Chromogranin A and Calcitonin Expression and with Ki67 Proliferative Index, but Not with Prognosis:

Abstract

Medullary thyroid carcinoma (MTC) has been shown to express Prospero homeobox protein 1 (Prox1), a transcription factor whose expression is altered in a variety of human cancers. We conducted a retrospective study on a series of 32 patients with MTC to test the correlation of Prox1 expression in MTC with clinicopathological features and to evaluate its prognostic significance. Correlation of Prox1 immunohistochemical expression with tumor size, proliferative index (Ki67), and calcitonin and CEA serum levels prior to surgery was tested for significant correlations. The difference in Prox1 and Ki67 immunohistochemical expression according to the immunohistochemical staining intensity of CEA, chromogranin A, and calcitonin was tested using the Kruskal-Wallis H test and linear regression analysis. The prognostic value of Prox1 and Ki67 for our patient cohort was assessed by Kaplan-Meier log rank survival analysis. We demonstrated a positive correlation between Prox1 expression and Ki67 index. Prox1 also showed significant difference in expression according to chromogranin A and calcitonin immunohistochemical expression, with higher Prox1 expression in tumors with stronger chromogranin A or calcitonin staining. Prox1 expression did not correlate with PFS or OS based on Kaplan-Meier log rank survival analysis. In conclusion, Prox1 expression in MTC is positively correlated with Ki67 and with the immunohistochemical expression of chromogranin A and calcitonin. However, the present study does not support a role for Prox1 in MTC prognosis.

A Previously Unrecognized Monocytic Component of Pheochromocytoma and Paraganglioma

A Previously Unrecognized Monocytic Component of Pheochromocytoma and Paraganglioma:

Abstract

We describe a consistently present, previously unrecognized, population of monocytes in pheochromocytomas and paragangliomas. Although sustentacular cells are generally recognized as a common component of these tumors, differential immunohistochemical staining for CD163 and S100 shows that monocytes can in fact be more numerous. These cells frequently resemble sustentacular cells topographically and cytologically, possibly explaining why they have not been previously noticed. They contribute to the tumor proteome and may have implications for tumor biology. No correlations were identifiable between the presence of these cells and any clinical characteristics of the tumors in the present study. A possible association with genotype is suggested by immunoblot showing high expression of CD163 protein in tumors with succinate dehydrogenase mutations.

molecular alterations in MDM2 in esophageal squamous cell carcinoma

<em>MDM2</em> copy number increase: <em>A poor prognostic, molecular event in esophageal squamous cell carcinoma</em>:

Publication date: Available online 18 April 2019

Source: Human Pathology

Author(s): Ryuichiro Sawada, Ritsuko Maehara, Taro Oshikiri, Tetsu Nakamura, Tomoo Itoh, Yuzo Kodama, Yoshihiro Kakeji, Yoh Zen

Summary

The present study aimed to elucidate the clinicopathological significance of molecular alterations in MDM2 in esophageal squamous cell carcinoma (ESCC). A total of 399 resected cases of ESCC were examined by dual-color in situ hybridization (DISH) for MDM2 and immunohistochemistry for p53 using tissue microarrays. Clinicopathological features were correlated with the MDM2 status. Among 362 cases with a successful DISH analysis, 19 (5%) and 13 (4%) had MDM2 amplification and chromosome 12 polysomy, respectively, and these were examined as an MDM2-positive group. A comparison between amplified and polysomic cases revealed that the latter were more strongly associated with pre-operative chemotherapy than the former. Sixteen out of 32 (50%) MDM2-positive cases had positive results in all tissue cores examined, indicating diffuse MDM2 alterations. Cases with the diffuse alteration of MDM2 were characterized by an advanced pT stage and extensive vascular infiltration. The relationship between MDM2 copy number increases and p53 mutations was weak, with the overexpression of p53 being similarly detected in MDM2-positive and MDM2-negative cases (59% vs. 49%; P = .267). Overall survival was shorter in patients with MDM2-positive ESCC than in those without MDM2 alterations (P = .033). The poor prognostic value of MDM2 alterations became more obvious when only diffusely altered cases were counted (P = .005). In conclusion, the present study revealed that MDM2 copy number increases occurred in 9% of ESCC cases, and MDM2 alterations, particularly diffuse abnormalities, were associated with a poor prognosis. MDM2-altered ESCC may achieve beneficial effects from MDM2-targeted therapy.

Survivability of rabbit amniotic fluid-derived mesenchymal stem cells post slow-freezing or vitrification

Survivability of rabbit amniotic fluid-derived mesenchymal stem cells post slow-freezing or vitrification:

Publication date: Available online 17 April 2019

Source: Acta Histochemica

Author(s): Barbora Kulikova, Michal Kovac, Miroslav Bauer, Maria Tomkova, Lucia Olexikova, Jaromir Vasicek, Andrej Balazi, Alexander V. Makarevich, Peter Chrenek

Abstract

This work aimed to evaluate the effect of two distinct cryopreservation procedures - conventional slow-freezing and vitrification, on survivability and mesenchymal marker expression stability of rabbit amniotic fluid-derived mesenchymal stem cells (rAF-MSCs). Cells at passage 2 were slowly frozen, using 10% of dimethylsulfoxide, or vitrified, using 40% of ethylene glycol, 0.5 M sucrose and 18% Ficoll 70. After three months storage in liquid nitrogen, viability, chromosomal stability, ultrastructure, surface and intracellular marker expression and differentiation potential of cells were evaluated immediately post-thawing/warming and after additional culture for 48–72 h. Our results showed decreased (P ≤ 0.05) viability of cells post-thawing/warming. However, after additional culture, the viability was similar to those in fresh counterparts in both cryopreserved groups. Increase (P ≤ 0.05) in the population doubling time of vitrified cells was observed, while doubling time of slow-frozen cells remained similar to non-cryopreserved cells. No changes in karyotype (chromosomal numbers) were observed in frozen/vitrified AF-MSCs, and histological staining confirmed similar differentiation potential of fresh and frozen/vitrified cells. Analysis of mesenchymal marker expression by qPCR showed that both cryopreservation approaches significantly affected expression of CD73 and CD90 surface markers. These changes were not detected using flow cytometry. In summary, the conventional slow-freezing and vitrification are reliable and effective approaches for the cryopreservation of rabbit AF-MSCs. Nevertheless, our study confirmed affected expression of some mesenchymal markers following cryopreservation.

Cyclophilin B promotes cell proliferation, migration, invasion and angiogenesis via regulating the STAT3 pathway in non-small cell lung cancer

Cyclophilin B promotes cell proliferation, migration, invasion and angiogenesis via regulating the STAT3 pathway in non-small cell lung cancer:

Publication date: Available online 17 April 2019

Source: Pathology - Research and Practice

Author(s): Mao-rong Teng, Jian-an Huang, Zheng-tai Zhu, Hua Li, Jiang-feng Shen, Quan Chen

Abstract

Lung cancer is the most common type of cancer and has become the leading cause of cancer-associated mortality worldwide. It has been reported that expression of Cyclophilin B was greatly elevated in the pancreatic cancer patient sera as compared with the healthy volunteer sera. This study aimed to investigate the role and regulatory mechanism of CypB in NSCLC progression. The expression levels of CypB was detected in NSCLC samples and cell lines by ELISA, western blot and immunohistochemistry assay. In addition, CCK8, colony formation, scratch and transwell assays were used to evaluate the proliferation, migration and invasion of A549 cells with CypB silencing. The expression of angiogenesis related proteins and pathway-related factors were detected by western blot. In NSCLC samples, CypB expression was upregulated. The expression of CypB was significantly reduced in the siRNA-cyclophilin B group. In addition, CypB silencing inhibited cell proliferation, migration and invasion. The expression of angiogenesis related proteins and pathway-related factors have also changed significantly. These findings suggested that CypB silencing may suppress the proliferation, invasion, migration and angiogenesis of A549 cells via inhibiting STAT3 pathway.

Circular RNAs as diagnostic biomarkers in gastric cancer: a meta-analysis review

Circular RNAs as diagnostic biomarkers in gastric cancer: a meta-analysis review:

Publication date: Available online 17 April 2019

Source: Pathology - Research and Practice

Author(s): Fei Jiang, Fanglan Hong, Muhammad Waseem Shah, Xiaobing Shen

Abstract

Purpose

Gastric cancer is a malignant tumor in the world and circRNA has a close connection with it. However, the effects of circRNA on gastric cancer is still not clear.

Methods

A comprehensive search of PubMed, Web of Science and Embase for published experimental studies about circRNA from 2013 to June 2018 was conducted with two investigators. Diagnostic OR (DOR) was calculated to evaluate the diagnostic efficacy by STATA 12.0.

Results

Total 11 studies were found, including 12 kinds of circRNAs, 11 in tissues, 5 in plasma, and all down regulated. The combined DOR and AUC (Area Under the Curve of Receiver Operating Characteristic) with their 95%CI were 8.778 [6.108, 12.614] and 0.81 [0.78, 0.84] respectively, indicating that circRNAs can reflect gastric cancer as well. Subgroup analysis revealed that circRNAs in plasma were higher than tissues as well as in subgroup with different sample sizes. We speculated that the heterogeneity of the literatures was mainly due to the different backgrounds of gastric cancer and the differences in experimental design and operation process. And the Deeks’ funnel map revealed there was no obvious public biasness in the literature.

Conclusion

CircRNAs have high sensitivity and specificity in the diagnosis of gastric cancer, and it may become an auxiliary diagnostic biomarker of gastric cancer.

B7-H3 and its role in bone cancers

B7-H3 and its role in bone cancers:

Publication date: Available online 17 April 2019

Source: Pathology - Research and Practice

Author(s): Lile He, Zhihong Li

Abstract

Most bone cancers have a high risk of metastasis, recurrence, and poor prognosis. Although conventional treatments are still the most important therapy, disadvantages still exist. Therefore, there is an unmet need to develop effective strategies. Immunotherapy is a promising therapy. Immunotherapies targeting checkpoints have proven to be successful, but B7-H3 (CD276, clusters of differentiation protein 276), a member of the B7-family of co-stimulatory molecules, is not being widely studied in bone cancers. This review summarized the studies on B7-H3 in bone cancers. 4 studies investigated B7-H3 expression in osteosarcoma, but there is no study on B7-H3 expression in chondrosarcoma. Two studies investigated the possibility to treat Ewing`s sarcoma through targeting the B7-H3 CAR (chimeric antigen receptors) T-cells or using anti-B7-H3 antibody. A study observed the growth of myeloma in B7-H3-deficient mice and the therapeutic effect of B7-H3 antibody and a study invested B7-H3 expression in myeloma patients. One study reported B7-H3 expression in osteoclastomas and one study investigated B7-H3 expression in chordoma tumor tissues. Two clinical trials are conducting on the therapy of osteosarcoma and myeloma using B7-H3 as a target. In conclusion, B7-H3 could be a target of bone cancers.

TRIP13 upregulation is correlated with poor prognosis and tumor progression in esophageal squamous cell carcinoma

TRIP13 upregulation is correlated with poor prognosis and tumor progression in esophageal squamous cell carcinoma:

Publication date: Available online 17 April 2019

Source: Pathology - Research and Practice

Author(s): Shouyin Di, Mingyang Li, Zhiqiang Ma, Kai Guo, Xiaofei Li, Xiaolong Yan

Abstract

Thyroid receptor-interacting protein 13 (TRIP13), a member of the AAA + ATPase super-family, has been proved to be upregulated and identified as a prognostic factor in multiple human cancers, However, the role of TRIP13 in esophageal squamous cell carcinoma (ESCC) and its clinic relevance remains unclear. In the present study, we performed database-mining and the detected TRIP13 expression in 158 tissue samples (79 ESCC tissue and 79 matched adjunct non-cancerous tissues). We further investigated the correlation between TRIP13 expression and clinicopathological features and overall survival. Univariate and multivariate Cox regression analyses were applied to evaluate the potential prognostic value of TRIP13 in ESCC patients. In addition, the mechanisms involved in TRIP13 tumor-promoting effect was investigated. Data showed that TRIP13 expression was significantly increased in ESCC tissues, compared with the matched adjunct non-cancerous tissues. Expression of TRIP13 is significantly correlated with T status (P = 0.027), lymphatic metastasis (P = 0.017), and clinical stages of ESCC (P = 0.009). Kaplan-Meier analyses showed that patients with high TRIP13 expression had poor overall survival (P = 0.0022). Multivariate analysis indicated that TRIP13 expression might be an independent prognostic factor in ESCC patients (HR, 1.778, 95 % confidence interval = 0.959-3.296, P = 0.028). Furthermore, downregulating TRIP13 in EC109 cell significantly attenuated the cell proliferation and progression, possibly by β-catenin regulated EMT pathway.

Conclusions: Our study demonstrated that TRIP13 might be a tumor promoting factor in ESCC and a promising prognostic indicator for ESCC patient.

miR-142-5p regulates pancreatic cancer cell proliferation and apoptosis by regulation of RAP1A

miR-142-5p regulates pancreatic cancer cell proliferation and apoptosis by regulation of RAP1A:

Publication date: Available online 18 April 2019

Source: Pathology - Research and Practice

Author(s): Rong Yao, Lijuan Xu, Bin Wei, Zhaoye Qian, Jiru Wang, Hongxia Hui, Yuan Sun

Abstract

Pancreatic cancer, one of the fatal and aggressive malignancies, leads the sixth cancer-associated death in China. microRNAs are believed to exert function in the diagnosis and treatment of pancreatic cancer. In the present study, we firstly found that miR-142-5p was downregulated in pancreatic cancer tumor tissues while Ras-related protein Rap-1 A (RAP1A) was upregulated compared with para-carcinoma non-tumor tissues. Then, we found that RAP1A could be a putative target gene of miR-142-5p by bioinformatics tool TargetScan. Furthermore, we conducted luciferase reporter assay, RT-qPCR, western blot and correlation analysis to demonstrate that miR-142-5p could negatively regulate RAP1A expression by binding to its 3’UTR. In addition, cell-counting kit 8 (CCK-8) and flow cytometry assays certified that miR-142-5p overexpression may inhibit pancreatic cancer cell proliferation but promote cell apoptosis; while the variation could be reversed by co-transfected with pcDNA3.1-RAP1A. Finally, miR-142-5p overexpression downregulated p-ERK1/2, phosphate p38 mitogen-activated protein kinases (p-p38); however, the variation induced by miR-142-5p mimic could be reversed by co-transfected with pcDNA3.1-RAP1A. In conclusion, our findings indicate that targeting miR-142-5p may provide a novel strategy for the treatment of pancreatic cancer.

Expression of programmed cell death-ligand 1 in oral squamous cell carcinoma and oral leukoplakia is associated with disease progress and CD8+ tumor-infiltrating lymphocytes

Expression of programmed cell death-ligand 1 in oral squamous cell carcinoma and oral leukoplakia is associated with disease progress and CD8+ tumor-infiltrating lymphocytes:

Publication date: Available online 18 April 2019

Source: Pathology - Research and Practice

Author(s): Xiao-Jie Chen, Ya-Qin Tan, Na Zhang, Ming-Jing He, Gang Zhou

Abstract

Objective

In recent years, monoclonal antibodies targeting programmed cell death-ligand 1 (PD-L1) have become a promising cancer immunotherapy. However, the role of PD-L1 in oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs), including oral leukoplakia (OLK), remains controversial. The aim of the present study was to investigate the expression level of PD-L1 in OSCC and OPMDs, and examine its relationship with CD8 expression and different clinicopathological features.

Method

Expression of PD-L1 and CD8 were conducted in 41 OSCC, 21 OLK, and 25 normal mucosa samples by immunohistochemistry. Then, the density of PD-L1 expression was measured, and its correlation with CD8 expression and different clinicopathological features was analyzed.

Results

PD-L1 protein was detected in 97.6% of OSCC, 61.9% of OLK, and 0% of normal tissues. PD-L1 was highly expressed in human OSCC tissue (P < 0.0001), when compared to both OLK and control tissues. PD-L1 positivity was significantly associated with CD8 density (P < 0.0001, r = 0.8491). The PD-L1 high expression OSCC group displayed a trend for improved overall survival (OS) and disease-free survival (DFS) compared to the low expression group, although the differences were not significant. Moreover, the expression level of PD-L1 in OSCC was positively correlated with the pathological grade (P < 0.0001), but it was independent of age, gender, smoking, drinking, tumor size, lymph node status, or recurrence (P > 0.05). Also, there was a significant upregulation of PD-L1 expression observed in the OLK group compared to the control group (P < 0.0001). PD-L1 positivity in OLK patients was associated with gender and smoking habits (P < 0.05), but it did not correlate with age, drinking, or dysplasia (P > 0.05).

Conclusion

The upregulation of PD-L1 may be associated with disease progress and CD8+ tumor-infiltrating lymphocytes in oral premalignant and malignant lesions.

Particularités des injections de toxine botulique pour le traitement esthétique du visage chez l’homme. Une mise au point de la littérature

Particularités des injections de toxine botulique pour le traitement esthétique du visage chez l’homme. Une mise au point de la littérature:

Publication date: Available online 17 April 2019

Source: Annales de Chirurgie Plastique Esthétique

Author(s): M. Haiun, L. Cardon-Fréville, F. Picard, J.-P. Meningaud, B. Hersant

Résumé

Introduction

Les injections de toxine botulique en médecine esthétique sont les produits les plus utilisés, devant l’acide hyaluronique, et la médecine esthétique est en augmentation constante, y compris dans la population masculine. L’objectif de cette mise au point était de montrer les spécificités décrites dans la littérature concernant les injections de toxine botulique chez l’homme.

Matériel et méthode

Une recherche systématique de la littérature a été réalisée grâce au moteur de recherche Pubmed. Les données ont ensuite été collectées afin de connaître les spécificités des injections de toxine botulique chez l’homme en fonction de la morphologie du visage masculin et des désirs de ces patients.

Résultats

Les études réalisées montrent qu’il est nécessaire d’injecter des doses plus importantes chez l’homme que chez la femme pour obtenir un résultat satisfaisant, en raison d’une masse musculaire plus importante. Cette mise au point donne le nombre de points à réaliser par zone d’injection, ainsi que le nombre de points à effectuer, en comparaison à la population féminine.

Conclusion

Les injections de toxine botulique à visée esthétique chez l’homme diffèrent par rapport à la femme. La prise en compte de ces particularités est indispensable à la satisfaction des patients.

Summary

Introduction

Botulinum toxin injections in aesthetic medicine are the most widely used products, ahead of hyaluronic acid, and aesthetic medicine is constantly increasing, including in the male population. The objective of this development was to show the specificities described in the literature concerning botulinum toxin injections in men.

Material and method

A systematic literature search was carried out using the Pubmed search engine. Data were then collected to determine the specificities of botulinum toxin injections in men according to the morphology of the male face and the wishes of these patients.

Results

The studies conducted show that it is necessary to inject higher doses in men than in women to obtain a satisfactory result, due to a higher muscle mass. This adjustment gives the number of points to be performed per injection site, as well as the number of points to be performed, compared to the female population.

Conclusion

Botulinum toxin injections for aesthetic purposes in men are different from those in women. Taking these particularities into account is essential to patient satisfaction.

The evaluation of the effects of open and closed rhinoplasty on the psychosocial stress level and quality of life of rhinoplasty patients

The evaluation of the effects of open and closed rhinoplasty on the psychosocial stress level and quality of life of rhinoplasty patients:

Publication date: Available online 18 April 2019

Source: Journal of Plastic, Reconstructive & Aesthetic Surgery

Author(s): Sinem Gökçe Kütük, Osman Kürşat Arıkan

Abstract

Aim

To investigate patient-reported functional and aesthetic outcomes and psycho-social distress levels in rhinoplasty patients with respect to technique, type and indications of surgery

Methods

A total of 90 patients (mean(SD) age: 27.4(6.5) years, 64.4% were females) undergoing rhinoplasty surgery were included prospectively. Data on Nasal Symptom Obstruction Evaluation (NOSE) scale for the functional outcome, the Rhinoplasty Outcome Evaluation (ROE) scale for the aesthetic outcome, and the Derriford Appearance Scale (DAS-24) for psychosocial outcomes were recorded preoperatively and in postoperative 1^st, 3^rd and 6^th months.

Results

No significant difference was noted in ROE or NOSE scores with respect to technique (open vs. closed), type (primary vs. secondary) and indication (functional vs. cosmetic) of rhinoplasty during study visits. Open vs. closed surgery, secondary vs. primary rhinoplasty and cosmetic vs. functional indication for rhinoplasty were associated with significantly higher DAS-24 scores at the preoperative visit (p<0.001 for each) and postoperative 1^st (p<0.001 for each) and 3^rd month (p<0.001, p<0.001 and p<0.01, respectively) visits. NOSE, ROE and DAS-24 scores significantly decreased from preoperative to postoperative period and from 1^st month to 3^rd and 6^th months of postoperative follow up in all patients, regardless of the rhinoplasty subgroup (p<0.001 for each).

Conclusion

In conclusion, our findings revealed favorable postoperative functional and aesthetic outcome and improved psycho-social distress in rhinoplasty patients with significantly improved NOSE, ROE and DAS-24 scores after rhinoplasty during the entire 6-month follow up, regardless of the technique (open vs. closed), type (primary vs. revision) and indication (cosmetic vs. functional) of rhinoplasty. Closed rhinoplasty may be a more preferable method due to less psycho-social distress.

White spots on tongue

https://tophealthjournal.com/5901/why-are-there-unusual-white-spots-on-your-tongue/

A tongue is often called "the strongest muscle of the body". It is made up of a group of muscles which allow us to taste the food, swallow, and talk. A healthy tongue is of pink color and covered with small nodules called papillae.

There are lots of small spots on the tongue for taste and sensation. Usually, they are not very noticeable. But if spots are of an unusual color, cause irritation, or other symptoms accompany them, they can be the sign of a health problem.

Tongue spots can be uncomfortable and painful, but they are usually not so serious. Often, they resolve without any treatment. But, some spots on the tongue, might signal a severe underlying problem which needs quick medical attention. You may identify the cause of some spots easily, but others require further examination.

Healthy tongue spots

There are four kinds of healthy spots which naturally appear on your tongue. The medical term used for these spots is papillae.

• Fungiform papillae; these are the small spots which appear all over the tongue. A person has 200 to 400 of these. Mostly, they are present at the tip and edges of your tongue. Each of these papillae contains 3 to 5 taste buds.

• Circumvallate papillae; are bigger spots which appear at the back of the tongue. They are slightly raised and are arranged in a 'v' shape. Usually, an individual has 7 to 12 spots, with each comprising thousands of taste buds.

• Foliate papillae; appear on the back and at the edges of the tongue. A person usually has around 20, each one containing hundreds of taste buds.

• Filiform papillae; are found at the front of the tongue. There are more of this type of papillae than any other and they do not contain taste buds.

The basic purpose of papillae is to help people to sense and taste with the tongue. However, nerves which send messages about flavor to the brain are connected to these taste buds. Papillae also play an important role in giving information about temperature, chewing food, and speaking.

Unusual white spots on the tongue

White spots on the tongue may be a harmless sign of adequate dehydration which needs no interference or it may appear as a disturbing feature of a primary organic condition. Most of the time, white spots are due to the gathering of bacteria, cellular debris, and dead cells which gives the tongue a white appearance.

Serious conditions which may present with white spots on the tongue comprise various fungal or bacterial infections or in some cases pre-cancerous disorders of the tongue or oral cavity. There are several infectious conditions which may present with different changes in tongue appearance. Leukoplakia is one of such conditions.

What is leukoplakia?

Leukoplakia is a Greek word which means 'white patch'. These white patches develop on the tongue, the inside of the cheek, or on the floor of the mouth. Basically, it is the mouth's reaction to continuing irritation of the mouth's mucous membranes. But its actual cause is unknown. Furthermore, these patches can occur at any stage of your life. But they are most common in senior adults.

"Hairy" leukoplakia is an uncommon form of leukoplakia. It is caused by the Epstein-Barr virus. However,this uncommon form is seen only in people infected with HIV, have AIDS, or AIDS-related complex.

It consists of uncertain, white patches on the tongue and less frequently, somewhere else in the mouth. Leukoplakia also has some resemblance with thrush which is an infection caused by the fungus Candida. It is common in adults, usually occurs if the immune system is not working suitably.

Causes of leukoplakia

As you use your tongue continually, it can be uncomfortable when you experience tongue problems, counting soreness and discoloration. Therefore, there are many causes for a number of common tongue signs. Causes of leukoplakia can include;

Irritation from rough teeth, fillings, or crowns, or ill-fitting dentures which rubs against cheek or gum

Sun exposure to the lips

Oral cancer (though rare)

Tobacco use, chronic smoking, or other pipe smoking

HIV or AIDS

Symptoms of leukoplakia

The white or gray colored patches commonly develop on your tongue in leukoplakia. But their occurrences in gums, a roof of the mouth, or the inside of the cheeks of mouth may also be a sign of leukoplakia.

These patches may develop slowly over weeks to months. They can be thick, slightly raised, and may ultimately take on a tough and rough texture. Usually, it is painless, but may be sensitive to heat, touch, spicy foods, or other irritation.

Diagnosis of leukoplakia

Your dentist may diagnose leukoplakia upon proper inspection; however, a biopsy will possibly be taken to rule out other causes, like oral cancer. For proper examination in the lab, a small piece of tissue from the lesion will be removed during biopsy. Moreover, a distressing agent will be used so that you will not feel any pain.

Treatment for Leukoplakia

Treatment for leukoplakia involves the removal of the source of irritation. For instance, if leukoplakia is caused by an irregular tooth or a rough surface on a denture or a filling, the tooth will be leveled and dental appliances fixed. If smoking is the cause of leukoplakia, you will be asked to reduce or stop smoking or using other tobacco products.

Usually, leukoplakia is harmless, and lesions clear in a few weeks or months after the removal of a source of irritation. If elimination of the source of irritation is ineffective and it does not reduce leukoplakia, the lesion may need to be removed surgically.

For that, the lesion can be removed either by your dentist or by an oral surgeon. However, hairy leukoplakia needs treatment with antiviral medication.

Tips

Here are some tips which can aid you to steer away from white spots on your tongue;

To reduce the chance or the recurrence of white spots on the tongue, try to maintain high dental care standards. Properly brushing your teeth and staying hydrated makes the environment inappropriate for bacterial growth. Antibacterial mouthwash can also be used for better results.

Avoid over spiced and acidic foods. Furthermore, try to avoid food that increases the chances of getting damaged. Spicy foods aggravate the lining of the tongue and mouth.

Avoid excessive alcohol intake and smoking as these could increase chances of oral cancers.

Limit sugar intake as sugar is a breeding place for oral bacteria.

Try to use home remedies such as salt water and baking soda to get rid of bacteria.

You can prevent or get rid of tongue problems by practicing some good dental hygiene. Brush and floss regularly. Moreover, regularly see your dentist for checkups and cleanings.

Avatar

Ilene Johnstone

Ilene Johnstone is an author at Top Health Journal. Currently, she is working as a biochemist and researcher. She is keen on emerging research, diet, new treatments, diseases and other trending topics in health. She delivers best regarding health to viewers in the form of interesting writings.

Sinus congestion: natural home remedies

https://www.medicalnewstoday.com/articles/323834.php

How can you clear up sinus congestion?

By Timothy Huzar Reviewed by J. Keith Fisher, M.D.

Home remedies Over-the-counter medication When to see a doctor Summary

Sinus congestion occurs when a condition causes fluid to become trapped in the sinuses, making them feel blocked and painful. Many natural home remedies can help a person feel better, including hydration, steam inhalation, and applying a warm, wet towel to the face.

A virus or cold is the most common cause of sinus congestion, but a bacterial infection can also occasionally cause it. According to the Centers for Disease Control and Prevention (CDC), a person with sinus congestion may experience:

headaches

a blocked or runny nose

a sore throat

tiredness

coughing

This article looks at six simple, natural home remedies for sinus congestion, as well as when to see a doctor.

Home remedies

There are many home remedies that a person can try to help relieve sinus congestion. These include:

1. Staying hydrated

The mucous membranes can become inflamed during sinus congestion. However, staying hydrated can help the membrane function correctly.

Drinking plenty of water and other fluids may help relieve the symptoms of sinus congestion. A person may find that keeping a water bottle close to them throughout the day can encourage them to drink more.

2. Breathing in steam

Inhaling steam which can help with sinus congestion

Inhaling steam can help with sinus congestion.

Breathing in steam can help keep the mucous membranes moist.

This is particularly important during winter or in colder climates.

This may help relieve the symptoms of sinus congestion and encourage the sinuses to unblock.

Running very hot water from a shower and breathing in the vapor may help unblock the sinuses and relieve symptoms.

It is also possible to use a humidifier for the same purpose.

3. Raising the head during sleep

To help encourage sinus blockages to clear, a person may consider raising their head during sleep. A person can use extra pillows to prop their head up.

Conversely, keeping the head level may result in a greater buildup of congestion overnight.

4. Using eucalyptus oil

Eucalyptus oil relieves the symptoms of sinus congestion. It may also help kill germs in and around the nasal passage that contribute to a sinus infection.

A person can use eucalyptus oil by applying it to tissue paper and sleeping next to it, or by adding it to hot water and inhaling the steam. However, if a person applies the hot water and eucalyptus oil mixture directly to the skin, it may cause burns.

Menthol-based oils are also popular, but they work by making a person feel as though they can breathe more easily. They do not unblock the congested sinuses.

5. Applying warm, wet towels

A warm, wet towel held against the face may help relieve the swelling and inflammation of sinus congestion.

It may also help keep the mucous membranes moist by breathing in moist air, which can help it function properly.

People can also soak a towel in warm water, wring it out, and drape it over their face in a way that is still comfortable for them to breathe through their mouth.

6. Trying a neti pot

oman using a neti pot to clear her nose of congestion

A neti pot can help to relieve the symptoms of sinus congestion.

Neti pots are small teapot-shaped devices that help a person pour a salt water solution into their nasal cavity.

This may help relieve the symptoms of sinus congestion by keeping the mucous membranes moist and functioning properly.

Neti pots may also help treat congestion by flushing out the sinuses and the buildup of any material causing a blockage. It is vital to follow instructions carefully.

The United States Food and Drug Administration (FDA) note that if a person has not properly cleaned the neti pot before using it, it might actually cause a sinus infection. People should clean neti pots using distilled, sterile, or previously boiled water that is free of harmful germs.

Over-the-counter medication

Nasal sprays that include a decongestant may be helpful in relieving congested sinuses.

However, Harvard Medical School point out that decongestants can also cause problems. For example, sometimes, congestion can become worse after a person stops using decongestants.

Taking painkillers may also help relieve pain due to sinus congestion.

If a person experiences side effects or the medication is not working, they should speak to a medical professional.

What is the best remedy for sinus drainage?

Draining the sinuses can help relieve congestion. Learn about the best ways to drain the sinuses here.

READ NOW

When to see a doctor

Though a person can usually resolve sinus congestion using home remedies, complications can arise. In these cases, seeing a medical professional is important.

The CDC recommend seeing a medical professional if a person has:

a temperature above 100.4F (38C)

symptoms that are worsening

symptoms that have not gone away after 10 days

frequent sinus issues

symptoms that over-the-counter (OTC) medication does not resolve

Summary

Sinus congestion most commonly occurs as a result of a cold, virus, or bacterial infection. Symptoms include a sore throat, a runny nose, and coughing, among others.

There are a number of simple home remedies that a person can try to help relieve these symptoms. These include inhaling steam, using eucalyptus oil, and staying hydrated. A person can also use OTC medications such as nasal sprays.

They should consider seeing a doctor when their symptoms do not go away or become worse, and the doctor will be able to work out what is causing a person's infection and prescribe appropriate medication if necessary.

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The sinuses are cavities that produce mucus. If a person has frontal sinusitis, the cavities just behind the eyes become inflamed, and the mucus cannot drain correctly. Infections, allergies, or long-term health issues may be responsible. Here, we examine the causes of frontal sinusitis and how treatments vary.

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How do I know if I have a cold or sinusitis?

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Common symptoms of a sinus infection

Sinus infections, or sinusitis, occur when a virus of bacteria enters the sinuses. The symptoms of sinusitis are similar to a cold, but it also involves a feeling of pressure and congestion in the sinuses. Read on for a list of common symptoms and treatments for sinus infections.

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How can you unblock your ear?

A clogged ear can happen for a variety of reasons. It can be a buildup of wax or caused by a cold or sinus infection. Thankfully, many cases of a clogged ear can be treated with some simple home remedies. These include ear irrigation, steam inhalation, or simply ear drops. Learn about home remedies plus what not to do.

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Everything you need to know about sinus infection

The sinuses behind the nose can become inflamed for a variety of reasons. This MNT Knowledge Center article explains the symptoms of sinus infection, also known as sinusitis. Sinus infection is one of the most commonly diagnosed infections in the U.S. This article shows how it can complicate and what types there are.

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FLU / COLD / SARS

COMPLEMENTARY MEDICINE / ALTERNATIVE MEDICINE

EAR, NOSE AND THROAT

Additional information

Article last reviewed by Wed 28 November 2018.

Visit our Flu / Cold / SARS category page for the latest news on this subject, or sign up to our newsletter to receive the latest updates on Flu / Cold / SARS.

All references are available in the References tab.

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Nasal mucus transplant

https://vancouversun.com/news/local-news/believe-it-or-snot-st-pauls-nasal-mucous-transplant-study-targets-inflamed-sinuses

Believe it or snot: St. Paul's nasal mucus transplant study targets inflamed sinuses

In the first study of its kind, patients with chronic sinus conditions will get transplanted nasal mucus from close relatives with healthy snot.

PAMELA FAYERMAN

Dr. Amin Javer, with study subject Maggie Bernet, shows how photodynamic therapy — a blue-light treatment that sterilizes the nasal cavity as it kills bacterial and viruses — works as part of the broader nasal mucous transplant study at St. Paul's Hospital.

ADJUST

COMMENT

There's healthy snot, then there's the other kind. And now those with good nasal mucus will be donating their slimy stuff to relatives suffering from chronically inflamed sinuses in a novel transplantation study at St. Paul's Hospital.

Study leader Dr. Amin Javer said in an interview the inspiration for the chronic rhinosinusitis (CRS) study is the success of fecal transplants for inflammatory bowel diseases and colitis caused by Clostridium difficile (C-diff). A member of his research team — epidemiologist Amee Manges — has been involved in several human microbiome studies related to the higher risk of hospitalized patients getting potentially deadly C-diff infections.

Just as in bowel disorders, good microorganisms — known as microbiome — in the sinus are disrupted and outnumbered by slimy groups of damaging bacterial and/or viral micro-organisms. Antibiotic therapy is not only often useless but often more damaging since antibiotics cut a wide swath, taking down good bacteria along with the bad.

The chronic sinus condition is common; it is said to affect up to 12 per cent of the North American population. Indeed, the hospital clinic gets 6,000 outpatient visits a year, many of them patients with the chronic sinus condition.

Ethics approval for the St. Paul's Hospital sino nasal microbiota transplant study, as it is called, has been granted by the hospital and the University of B.C. But Javer is waiting for final approval from Health Canada, which he expects to get next month.

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The study aims to answer whether transplants are both beneficial and safe in patients with the chronic condition. The working hypothesis is that inflammation, mucous discharge and recurring infections will indeed be improved by renewing and replenishing the sinus microbiome with healthy snot from donors.

What would recovery look like? No more constant coughing, no more blocked nasal passages, no more dripping from their noses, no more headaches, sinus infections, fatigue and poor sleep, among many other symptoms.

A patient getting photodynamic therapy with a blue light that sterilizes sinuses by killing bacterial and viral germs. (Photo: Handout)

A patient getting photodynamic therapy with a blue light that sterilizes sinuses by killing bacterial and viral germs. HANDOUT

Potential donors are now being screened and patients enrolled in the non-transplant arm of the study. Those patients will receive only photodynamic therapy — a blue-light treatment that sterilizes the nasal cavity as it kills all bacteria and viruses. While two-thirds of patients who get such treatment reportedly improve, the effect is short term. Just like antibiotics, it doesn't distinguish between beneficial germs and bad ones, so a small number of patients actually get worse.

A second group in the study will be randomized to phototherapy plus the transplant while a third will get only the transplant. About 200 participants will be enrolled in the study.

Former nurse Pat Taylor is one of the participants in the trial. She's been randomized to the branch of patients receiving only blue-light therapy. The Victoria resident said most people have no idea how life-altering and disabling chronic sinusitis is.

"It is financially, physically and emotionally debilitating with a poor quality of life. Many health professionals know little or nothing about CRS, so many people go undiagnosed," she said, adding that patients often bounce around between specialists like respirologists and allergists, often to no avail.

Javer echoes her sentiments. "Chronic sinusitis has been shown by research to totally ruin the quality of life of patients. It's a disease that creates so much emotional distress for people. I've got patients who tell me they'd rather be dead than endure all these symptoms. One patient from Prince George recently said to me that if I couldn't fix him, he'd rather I killed him."

Javer said he's convinced a "sinus probiotic" is needed to repopulate unhealthy sinus cavities with healthy microbes. Without a beneficial probiotic, harmful pathogens find a way to return and multiply in the nasal cavity, ensuring the recurrence of the sinus disorder.

'We think the transplants using healthy donor microbiome could drastically improve the long-term health of those with diseased sinuses," he said, adding that a recently started study in Sweden is also exploring the use of sinus microbiome transplants. In that study, phototherapy is not being used and no results have yet been reported.

Javer said research has not yet pointed to the cause of the sinus disorder but it starts when something alters the environment in the nasal/sinus cavity.

"It can be a virus or a cold that starts this cascade of symptoms, and what's worse is patients get antibiotics from their family doctors and the vast majority of them don't need them," said Javer. "Prescribing oral antibiotics when you aren't sure they are needed can be the worst thing you can do because they can alter the microbiome."

The $300,000 study is funded through private donations to a charitable foundation that Javer established at St. Paul's Hospital. The funds are earmarked for sinus disorders.

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Watch out for the symptoms of head and neck cancer - Make Sense Campaign

https://www.hindustantimes.com/brandstories/make-sense/watch-out-for-the-symptoms-of-head-and-neck-cancer/

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Be head and neck cancer aware

« HOME PAGE Dr. Vinayak Munirathnam

ARTICLE

Watch out for the symptoms of head and neck cancer

According to oncologist, a lump in the neck can be the first sign.

By Dr. Vinayak MunirathnamApr 19,2019 8:30 IST

Head and neck cancers are curable if detected on time. Fortunately, these cancers produce symptoms early. Here are some of them.

• A lump in the neck that lasts for more than two weeks. Not all lumps are cancerous. But a lump in the neck can be the first sign of cancer of the mouth, throat, voice box (larynx), or salivary glands.

• Such lumps are generally painless. Commonly, antibiotics are prescribed as an initial mode of treatment under the assumption that the lumps have been caused due to an infection. If the lump persists or continues to grow despite the use of antibiotics, further investigation is essential.

• Most cancers in the voice box cause a change in voice. If you find your voice becoming hoarse or if the change lasts for more than two weeks, you must visit an ENT.

• Cancers of the mouth or tongue cause a sore or swelling that doesn't go away or may or may not be painless.

• Bleeding may occur, but often not until late. If an ulcer or swelling is accompanied by lumps in the neck, you should seek medical advice.

• Tumors in the nose, mouth, or throat can lead to blood in your saliva or phlegm. If this continues for more than a few days, you should consult a doctor.

• Cancer of the throat may make swallowing solid foods (and sometimes liquids) difficult. You may also end up throwing up the food.

• Most squamous cell cancers occur in the lower lip and ear. They might present as a sore which does not heal.

• Constant pain in or around the ear when you swallow can be a sign of infection or tumor growth in the throat.

Nearly 90% of head and neck cancers are caused due to tobacco and alcohol consumption. Therefore, you must quit their usage immediately. In adults who do not smoke or drink, cancer of the mouth and throat can occur as a result of HPV infection. Prolonged exposure to sunlight is linked to lip cancer.

This article has been written by Dr. Vinayak Munirathnam, MBBS,MD,DM,Consultant Medical Oncologist, HCG Hospitals, Bangalore.

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The above content has not been created by any HT Journalist or editorial team.

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Clinical Trials

Incentivizing healthy lifestyle behaviors to reduce cardiovascular risk in people with serious mental illness: An equipoise randomized controlled trial of the wellness incentives program

Publication date: June 2019

Source: Contemporary Clinical Trials, Volume 81

Author(s): Sarah I. Pratt, Mary F. Brunette, Rosemarie Wolfe, Emily A. Scherer, Haiyi Xie, Stephen Bartels, Joelle C. Ferron, Kelley Capuchino

Abstract

Background

Medicaid recipients with serious mental illness die 25–30 years earlier than people in the general population due to health conditions that are modifiable through lifestyle changes. Cardiovascular diseases from excess weight, smoking, and sedentary lifestyle contribute substantially to this life expectancy disparity. The current study evaluated the impact of incentives on participation in weight management programming (for overweight and obese adults) and smoking cessation treatment (for regular smokers).

Methods

Participants were Medicaid recipients with disabling mental illness receiving services at any one of 10 community mental health centers across New Hampshire. Using an equipoise stratified randomized design, n = 1348 were enrolled and assigned to one of four weight management programs (Healthy Choices Healthy Changes: HCHC) and n = 661 were enrolled and assigned to one of three smoking cessation interventions (Breathe Well Live Well: BWLW). Following assignment to an intervention, participants were randomized to receive financial incentives (to attend weight management programs, or to achieve abstinence from smoking) or not. Data were collected at baseline and every 3 months for 12 months.

Discussion

New Hampshire's HCHC and BWLW programs were designed to address serious and preventable health disparities by providing incentivized health promotion programs to overweight/obese and/or tobacco-smoking Medicaid beneficiaries with mental illness. This study was an unprecedented opportunity to evaluate an innovative statewide implementation of incentivized health promotion targeting the most at-risk and costly beneficiaries. If proven effective, this program has the potential to serve as a national model for widespread implementation.

Proactive text messaging (GetReady2Quit) and nicotine replacement therapy to promote smoking cessation among smokers in primary care: A pilot randomized trial protocol

Publication date: May 2019

Source: Contemporary Clinical Trials, Volume 80

Author(s): G.R. Kruse, E. Park, J.E. Haberer, L. Abroms, N.N. Shahid, S.E. Howard, Y. Chang, J.S. Haas, N.A. Rigotti

Abstract

Introduction

Most smokers see a physician each year, but few use any assistance when they try to quit. Text messaging programs improve smoking cessation in community and school settings; however, their efficacy in a primary care setting is unclear. The current trial assesses the feasibility and preliminary clinical outcomes of text messaging and mailed nicotine replacement therapy (NRT) among smokers in primary care.

Methods

In this single-center pilot randomized trial, eligible smokers in primary care are offered brief advice by phone and randomly assigned to one of four interventions: (1) Brief advice only, (2) text messages targeted to primary care patients and tailored to quit readiness, (3) a 2-week supply of nicotine patches and/or lozenges (NRT), and (4) both text messaging and NRT. Randomization is stratified by practice and intention to quit. The text messages (up to 5/day) encourage those not ready to quit to practice a quit attempt, assist those with a quit date through a quit attempt, and promote NRT use. The 2-week supply of NRT is mailed to patients' homes.

Results

Feasibility outcomes include recruitment rates, study retention, and treatment adherence. Clinical outcomes are assessed at 1, 2, 6, and 12-weeks post-enrollment. The primary outcome is ≥1self-reported quit attempt(s). Secondary clinical outcomes include self-reported past 7- and 30-day abstinence, days not smoked, NRT adherence, and exhaled carbon monoxide.

Conclusions

This pilot assesses text messaging plus NRT, as a proactively offered intervention for smoking cessation support in smokers receiving primary care and will inform full-scale randomized trial planning.

Trial registration

ClinicalTrials.gov NCT03174158.

Specialized tobacco quitline and basic needs navigation interventions to increase cessation among low income smokers: Study protocol for a randomized controlled trial

Publication date: May 2019

Source: Contemporary Clinical Trials, Volume 80

Author(s): Amy McQueen, Christina Roberts, Rachel Garg, Charlene Caburnay, Qiang Fu, Jacob Gordon, Terry Bush, Robin Pokojski, Tess Thompson, Matthew Kreuter

Abstract

Smoking in the United States follows a clear socioeconomic gradient: low-income Americans smoke more and quit less than those with more education and income. Evidence-based interventions like tobacco quitlines are designed to make effective cessation services available on a population basis to all smokers. However, these interventions do not address many of the unique challenges faced by low-income smokers, including unmet basic needs like food, housing, personal safety and money for necessities that often supersede health needs. Research is needed to maximize the use and effectiveness of tobacco quitlines in low-income populations. This paper details the rationale, design and methods for a 2 × 2 randomized controlled trial currently underway comparing the effects of Standard and Specialized Tobacco Quitlines with and without Basic Needs Navigation on intervention engagement and smoking cessation among low-income smokers. Smokers are recruited from United Way 2-1-1 in Missouri and all participants receive tobacco quitline services from Optum. Quitline and navigation services are provided for 3 months. Participants complete telephone surveys at baseline, 3- and 6-month follow up. The primary study outcome is self-reported 7-day point prevalence abstinence at 6-month follow up. Embedding the study in practice agencies will accelerate dissemination and scalability should our findings demonstrate intervention effectiveness.

Dose-response analysis of ranibizumab as-needed regimens for visual improvement in patients with diabetic macular edema using a modelling approach

Publication date: May 2019

Source: Contemporary Clinical Trials, Volume 80

Author(s): Yuan Xiong, Etienne Pigeolet, Zufar Mulyukov, Philippe Margaron, Amy Racine, Andreas Clemens

Abstract

Background

Ranibizumab and aflibercept are anti-vascular endothelial growth factor therapies for diabetic macular edema (DME) but have only been directly compared in one study: the Protocol T study, a 24-month randomized controlled trial which compared the safety and efficacy of three anti-VEGF agents (ranibizumab 0.3 mg, aflibercept 2.0 mg and bevacizumab 1.25 mg). The ranibizumab dose used in Protocol T is not licensed for use outside of the US, where a higher ranibizumab dose of 0.5 mg is approved. Therefore, the relevance of the head-to-head Protocol T study findings to healthcare providers in Europe is limited. The purpose of this research was to predict the visual outcomes that may have been achieved in Protocol T with ranibizumab 0.5 mg.

Methods

A simplified dose-response model was constructed to describe the relationship between average monthly dose and one-year best corrected visual acuity (BCVA) change from baseline. A linear mixed effects model was evaluated and Bayesian Monte-Carlo Markov chains method was used to estimate the model parameters.

Results

If ranibizumab 0.5 mg PRN had been studied in Protocol T, it would have resulted in a BCVA gain of 14–15 early treatment diabetic retinopathy study (ETDRS) letters; 3–4 letters more than the actual BCVA gain reported with ranibizumab 0.3 mg PRN. In Protocol T patients with poor baseline BCVA (<69 letters), a similar additional letter gain would have been achieved.

Conclusion

The relevance of the Protocol T study findings are limited due to the use of ranibizumab 0.3 mg PRN which, based on the modelling approach reported herein, resulted in sub-optimal visual gains.

Design and recruitment of the randomized order safety trial evaluating resident-physician schedules (ROSTERS) study

Publication date: May 2019

Source: Contemporary Clinical Trials, Volume 80

Author(s): Terri Blackwell, Dana R. Kriesel, Eric Vittinghoff, Conor S. O'Brien, Jason P. Sullivan, Natalie C. Viyaran, Shadab A. Rahman, Steven W. Lockley, Laura K. Barger, Ann C. Halbower, Sue E. Poynter, Kenneth P. Wright, Pearl L. Yu, Phyllis C. Zee, Christopher P. Landrigan, Charles A. Czeisler, Katie L. Stone, for the ROSTERS Study Group

Abstract

Introduction

While the Accreditation Council for Graduate Medical Education limited first year resident-physicians to 16 consecutive work hours from 2011 to 2017, resident-physicians in their second year or higher were permitted to work up to 28 h consecutively. This paper describes the Randomized Order Safety Trial Evaluating Resident-physician Schedules (ROSTERS) study, a clustered-randomized crossover clinical trial designed to evaluate the effectiveness of eliminating traditional shifts of 24 h or longer for second year or higher resident-physicians in pediatric intensive care units (PICUs).

Methods

ROSTERS was a multi-center non-blinded trial in 6 PICUs at US academic medical centers. The primary aim was to compare patient safety between the extended duration work roster (EDWR), which included shifts ≥24 h, and a rapidly cycling work roster (RCWR), where shifts were limited to a maximum of 16 h. Information on potential medical errors was gathered and used for classification by centrally trained physician reviewers who were blinded to the study arm. Secondary aims were to assess the relationship of the study arm to resident-physician sleep duration, work hours and neurobehavioral performance.

Results

The study involved 6577 patients with a total of 38,821 patient days (n = 18,749 EDWR, n = 20,072 RCWR). There were 413 resident-physician rotations included in the study (n = 203 EDWR, n = 210 RCWR). Resident-physician questionnaire data were over 95% complete.

Conclusions

Results from data collected in the ROSTERS study will be evaluated for the impact of resident-physician schedule roster on patient safety outcomes in PICUs, and will allow for examination of a number of secondary outcome measures.

ClinicalTrials.gov Identifier: NCT02134847

Evaluation of worldwide clinical trials by gender: An FDA perspective

Publication date: May 2019

Source: Contemporary Clinical Trials, Volume 80

Author(s): Emily Ayuso, Ruth J. Geller, Junyang Wang, John Whyte, Marjorie Jenkins

Abstract

Introduction

The US Food and Drug Administration (FDA) has undertaken efforts to promote representation of women in clinical trials. The objectives of this research are to assess women's participation in clinical trials from a global perspective and to analyze the demographic characteristics of clinical trial participants.

Methods

FDA's Center for Drug Evaluation and Research-Professional Affairs and Stakeholder Engagement (CDER/PASE) and Office of Women's Health (OWH) collaborated to evaluate demographic data (race, ethnicity, gender, and age) of pivotal trials of New Molecular Entities (NMEs) approved in 2015–2016 by geographic location. One hundred fifty-four pivotal clinical trials supporting 66 NMEs were identified, and the research team analyzed demographic characteristics of 131,749 participants from 70 countries.

Results

U.S. sites contributed 31% of the 131,749 study participants. On the country level, the United States contributed the largest number of participants and other individual countries contributed 5% or less of the total trial population. Overall, 43% (n = 56,272) of the 131,747 clinical trial participants were women. Of the 40,833 U.S. participants, 49% were women as compared to 40% of the 90,914 non-U.S. participants. Similar levels of participation were seen after the exclusion of sex-specific drug indications, and by therapeutic area for U.S. and non-U.S. sites.

Conclusions

Clinical trials are becoming increasingly multi-national, and the increasing representation of women across countries is promising. FDA approval processes ensure that global data used in the drug approval process meets regulatory standards and that data can be generalized to the U.S. population.

Care partner problem solving training (CP-PST) for care partners of adults with traumatic brain injury during inpatient rehabilitation: Study protocol for a multisite, randomized, single-blind clinical feasibility trial

Publication date: May 2019

Source: Contemporary Clinical Trials, Volume 80

Author(s): Shannon B. Juengst, Valeria Silva, Yelena Goldin, Keith Cicerone, Jean Lengenfelder, Nancy Chiaravalloti, Simon Driver, David Mellick, Georgianna Dart, Chung Lin Kew, Andrew Nabasny, Kathleen R. Bell

Abstract

Traumatic brain injury (TBI) often leads to immediate and chronic functional impairments that affect care partners, or those providing physical and/or emotional support to individuals with TBI. The many challenges associated with being a care partner often lead to caregiver burden and can compromise the well-being and quality of life of care partners and individuals with TBI under their care. Equipping care partners with problem-solving skills could facilitate and sustain their transition into this supportive role. Problem-solving training (PST) has demonstrated efficacy for providing such skills to care partners of individuals with TBI after discharge from inpatient rehabilitation. We propose that PST delivered to care partners during inpatient rehabilitation of individuals with TBI will provide care partners with the skills to manage their caregiving roles across the transition from hospital to home. Herein, we describe the methodology of a current randomized controlled trial that examines the feasibility and efficacy of PST plus TBI education compared to TBI education alone to improve care partner burden, emotional distress, and adaptive coping when delivered during the inpatient rehabilitation stay of individuals with moderate-severe TBI.

Design and patient characteristics of the randomized controlled trial TExT-MED + FANS A test of mHealth augmented social support added to a patient-focused text-messaging intervention for emergency department patients with poorly controlled diabetes

Publication date: May 2019

Source: Contemporary Clinical Trials, Volume 80

Author(s): Elizabeth Burner, Janisse Mercado, Antonio Hernandez-Saenz, Anne Peters, Lourdes Baezconde-Garbanati, Sanjay Arora, Shinyi Wu

Abstract

Although diabetes is a nationwide epidemic, US Latinos are a particularly vulnerable population. Culturally appropriate interventions can combat this disparity, especially those that increase social support. However, these interventions face significant cost and time barriers, which mHealth (mobile health) may overcome. This trial examines the benefit of adding social support to an existing text-message based, patient-focused mHealth intervention for emergency department patients with poorly controlled diabetes. Family members and friends of patients were randomized to mHealth augmented social support training (daily text-messages that synchronize with the patient messages) or a pamphlet based training (the same content mailed to their house.) We hypothesize that patients who received mHealth augmented social support will have a larger improvement in diabetes management (glycosylated hemoglobin or A1C) than those receiving standard support at six-months, and that improvement will be sustained at twelve-months. Secondary patient outcomes are clinical (weight, blood pressure), behavioral (medication adherence, self-care activities) and psychosocial (general and diabetes-specific social support, self-efficacy, diabetes-related distress, depression, fatalism and quality of life). We screened 2004 patients and enrolled 166 patient/supporter dyads. 70% of patients are Spanish-speaking, 51% female, with a mean A1C of 10.8. We employed innovative measures to remotely enroll family members and support a bilingual population, which will assist other investigators in design of similar trials. The findings of our trial will have real-world applicability for clinicians, health system administrators, health educators and mHealth developers who aim to improve the health of this vulnerable population.

Social incentives to encourage physical activity and understand predictors (STEP UP): Design and rationale of a randomized trial among overweight and obese adults across the United States

Publication date: May 2019

Source: Contemporary Clinical Trials, Volume 80

Author(s): Joseph D. Harrison, Jeremy M. Jones, Dylan S. Small, Charles A.L. Rareshide, Gregory Szwartz, David Steier, James Guszcza, Pameljit Kalra, Brian Torio, Gregory Reh, Victoria Hilbert, Mitesh S. Patel

Abstract

Background

Less than half of adults in the United States (US) obtain the recommended level of physical activity. Social incentives, the influences that impact individuals to adjust their behaviors based on social ties or connections, are ubiquitous and could be leveraged within gamification interventions to provide a scalable, low-cost approach to increase engagement. Gamification, or the use of game design in non-game situations, is commonly used in the real world, but in most cases has not appropriately leveraged principles from theories of health behavior.

Methods

We are conducting a four-arm, randomized, controlled trial of 602 overweight and obese adults to evaluate the effectiveness of gamification interventions that leverage insights from behavioral economics to enhance either supportive, competitive, or collaborative social incentives. Daily step counts are monitored using wearable devices that transmit data to the study platform. Participants established a baseline step count, selected a step goal increase, and then were randomly assigned to control or one of three interventions for a 24-week intervention and 12-week follow-up period. To understand predictors of strong or poor performance, we had participants complete validated questionnaires on a range of areas including their personality, risk preferences, social network, and habits relating to physical activity, eating, and sleep. Trial enrollment was conducted in partnership with Deloitte Consulting and included employees from 40 states across the US.

Conclusion

The STEP UP Trial represents a scalable model and interventions found to be effective could be deployed more broadly to increase physical activity.

Trial registration

Clinicaltrials.gov Identifier: NCT03311230

Effectiveness of shortened time interval to postpartum visit in improving postpartum attendance: Design and rationale for a randomized controlled trial

Publication date: Available online 18 April 2019

Source: Contemporary Clinical Trials

Author(s): Saba W. Masho, Timothy O. Ihongbe, Wen Wan, Whitney C. Graves, Nicole Karjane, Pamela Dillon, Gloria Bazzoli, Elizabeth McGee

Abstract

Background/Aims

Recent evidence suggests that there are numerous benefits to scheduling postpartum visits as early as 3 weeks post-delivery. However, findings are not conclusive due to methodological limitations. This report discusses the unique aspects of a randomized controlled trial's (RCT) design, intervention, and strategies to maintain participant retention.

Methods

This study was a four-year, prospective, open-label RCT conducted at the Virginia Commonwealth University Medical Center. Women who recently delivered a healthy, full-term baby vaginally, were randomized to receive a 3–4 or 6–8 weeks postpartum appointment and were followed for 18 months.

Results

A total of 364 women participated in this study. A large proportion of women were retained in the study as demonstrated by the high completion rates at the 18-month follow-up interview (Total sample: 87.6%; 3–4 weeks group: 88.0%; 6–8 weeks group: 87.3%). Similarly, high adherence to the protocol-directed postpartum visit schedule was reported in the overall study sample (79.7%), as well as in the 3–4 (70.5%) and 6–8 (90.0%) week postpartum groups.

Conclusion

The study design offered unique features which ensured excellent participant completion and adherence rates, despite the presence of hard-to-track women who typically do not return for their postpartum visits.

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00306932607174,00302841026182,alsfakia@gmail.com

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