Characterisation and prognostic value of tertiary lymphoid structures in oral squamous cell carcinoma

Background

Oral squamous cell carcinomas are often heavily infiltrated by immune cells. The organization of B-cells, follicular dendritic cells, T-cells and high-endothelial venules into structures termed tertiary lymphoid structures have been detected in various types of cancer, where their presence is found to predict favourable outcome. The purpose of the present study was to evaluate the incidence of tertiary lymphoid structures in oral squamous cell carcinomas, and if present, analyse whether they were associated with clinical outcome.

Methods

Tumour samples from 80 patients with oral squamous cell carcinoma were immunohistochemically stained for B-cells, follicular dendritic cells, T-cells, germinal centre B-cells and high-endothelial venules. Some samples were sectioned at multiple levels to assess whether the presence of tertiary lymphoid structures varied within the tumour.

Results

Tumour-associated tertiary lymphoid structures were detected in 21 % of the tumours and were associated with lower disease-specific death. The presence of tertiary lymphoid structures varied within different levels of a tissue block.

Conclusions

Tertiary lymphoid structure formation was found to be a positive prognostic factor for patients with oral squamous cell carcinoma. Increased knowledge about tertiary lymphoid structure formation in oral squamous cell carcinoma might help to develop and guide immune-modulatory cancer treatments.

     

The role and prognostic value of apoptosis in colorectal carcinoma

Background

Alterations to apoptosis are a common occurrence in human tumours. The aim of our study was to determine the influence of apoptotic variations on the carcinogenesis and prognosis of colorectal carcinomas (CRCs).

Methods

A TUNEL assay was performed on archival material from 103 colorectal carcinomas, 26 adenomas and 20 samples of normal epithelia.

Results

The number of apoptotic cells was higher in CRCs (1.09?±?0.13) than in adenomas (0.38?±?0.23, p?=?0.059) and normal epithelium (0.06?±?0.04, p?=?0.001). In addition, the apoptotic index (AI) was greater in metastatic disease (stage IV) than in other stages (p?=?0.017). No relationship was found between apoptotic rates and age, gender or tumour grade. However, patients with tumours that showed higher AI values had a significantly lower disease-free survival (DFS) and overall survival (OS) than those with tumours that had lower AIs (p?=?0.020 and p?=?0.027). In a multivariate Cox proportional hazards model, AI remained a significant independent predictor of survival.

Conclusions

We conclude that disregulated apoptosis is an important event during CRC development and progression. Higher AIs are associated with more aggressive tumours and a poorer prognosis for patients with CRC.

     

Lack of MMP-9 expression is a marker for poor prognosis in Dukes’ B colorectal cancer

Background

Matrix metalloproteinases (MMPs) play a role in cancer progression by degrading extracellular matrix and basement membranes, assisting in tumour neovascularization and in supporting immune response in cancer.

Methods

We studied the prognostic value of immunohistochemical expression of MMP-2, MMP-8, and MMP-9 in a series of 619 colorectal cancer patients using tissue microarray specimens.

Results

Of the samples, 56% were positive for MMP-2, 78% for MMP-8, and 60% for MMP-9. MMP-9 associated with low WHO grade (p?<?0.001). In univariate analysis of Dukes’ B tumours, MMP-9 negativity associated with poor survival (p?=?0.018), and MMP-9 positivity was an independent prognostic marker in multivariate analysis of these tumours (p?=?0.034).

Conclusion

Negative MMP-9 expression can predict poor prognosis in Dukes’ B colorectal tumours and may prove useful for identifying patients, who should be offered adjuvant treatment.

     

Ethical Assessment of Human Embryonic Stem Cell Research According to Turkish Muslim Scholars: First Critical Analysis and Some Reflections

Background

Turkey, with a Muslim population of officially over 99 %, is one of the few secular states in the Muslim world. Although state institutions are not based on Islamic juridical and ethical norms, the latter play a significant role in defining people’s attitudes towards controversial issues in the modern world, especially when backed by opinions of Muslim scholars living in Turkey. Accordingly, opinions of Muslim scholars undoubtedly have an important effect on bioethical decisions made by institutions and individuals.

Objective(s)

To explore the ethical positions of Muslim scholars living in Turkey and their arguments used in the ethical assessment of embryonic stem cell research; to discuss the biological-moral tensions arising in medical research on human embryos.

Design

Qualitative study.

Setting

Muslim scholars located in different parts of Turkey.

Methods

Qualitative method, involving the collection of opinions of various scholars, by means of 15 individual semi-structured interviews, evaluated using thematic qualitative analysis.

Results

Positions regarding embryonic stem cell research differ among Muslim scholars in Turkey. On the other hand, even where positions are similar, they are often supported by different arguments.

Conclusion

Despite the heterogeneity of the arguments presented, the dominant position considers embryonic stem cell research as morally acceptable.

     

Deficiencies in elements involved in TLR4-receptor signalling in RBL-2H3 cells

Objective

RBL-2H3 cells express Toll-like receptors, including TLR4. This study aims to assess various aspects of the TLR4 pathway.

Methods

RBL-2H3 cells were indirectly stained for cell surface TLR4, 25 CD14 and intracellular MyD88 proteins and analysed through flow cytometry for single-colour staining.

Results

While TLR4-receptors are expressed in RBL-2H3 cells, associated elements involved in the signaling pathway, CD14 and MyD88, are not.

Conclusion

Care should be taken if RBL-2H3 cells are used to study aspects of the innate immune system in mast cells.

     

Thymustumoren

Introduction

Thymic tumors including thymomas, thymic carcinomas, and thymic carcinoid tumors are rare tumors with an incidence of 0.13/100,000.

Materials and methods

A literature search was performed to identify recent findings on epidemiology, classification, and various therapeutic approaches.

Results

These tumors with a wide spectrum of histologic and biologic features may be clinically unapparent for a long time or show a very aggressive behavior with local invasion and distant metastases. Surgical resection is the mainstay in stage I and II thymomas, whereas in stage III thymomas and in thymomas with pleural dissemination surgery in context of a multimodal treatment should be discussed. Thymic tumors are chemoreactive. Targeted therapies show poor results and should only be considered in the palliative situation after failure of chemotherapy.

Conclusion

The new TNM (T: tumor, N: node, M: metastasis) classification of thymic tumors will help to identify the best treatment options.

     

A rare case of poorly differentiated thyroid carcinoma probably arising from a nodular goiter

Background

Some poorly differentiated thyroid carcinomas (PDTC) arise from pre-existing, well-differentiated carcinomas of follicular cell origin; however, others most likely arise de novo. The case of a PDTC adjacent to a pre-existing nodular goiter is very rare.

Case presentation

A patient had a PDTC, a widely invasive, cellular tumor with cells that lacked the nuclear features of a papillary thyroid carcinoma. Carcinoma cells were arranged in trabecular, solid, and microfollicular histological patterns and displayed high mitotic activity. A nodule partially encapsulated in a thick fibrous capsule was found adjacent to the PDTC. The nodule was composed of small or dilated follicles, without papillary carcinoma-like nuclear features, that were consistent with a nodular goiter. The PDTC showed a high Ki-67 labeling index and an NRAS gene mutation (codon 61, Q61K).

Conclusion

These results support our diagnosis of a PDTC, probably arising from a nodular goiter.

     

<Emphasis Type="Italic">Helicobacter bilis</Emphasis>-Associated Suppurative Cholangitis in a Patient with X-Linked Agammaglobulinemia

?

Helicobacter bilis is a commensal bacterium causing chronic hepatitis and colitis in mice. In humans, enterohepatic Helicobacter spp. are associated with chronic hepatobiliary diseases.

Purpose

We aimed at understanding the microbial etiology in a patient with X-linked agammaglobulinemia presenting with suppurative cholangitis.

Methods

16S rDNA PCR directly performed on a liver biopsy retrieved DNA of H. bilis.

Results

Clinical outcome resulted in the normalization of clinical and biological parameters under antibiotic treatment by a combination of ceftriaxone, metronidazole, and doxycyclin followed by a 2-week treatment with moxifloxacin and a 2-month treatment with azithromycin.

Conclusion

In conclusion, these data suggest a specific clinical and microbiological approach in patients with humoral deficiency in order to detect H. bilis hepatobiliary diseases.

     

Glücklich als Paar – glücklicher Schlaf?

Background

Millions of people share a bed with their partner. Sleep und relationship could possibly influence each other.

Objectives

To identify and discuss connections between relationship and sleep quality.

Methods

Review of the literature in electronic databases.

Results

Conflict and violence in relationships lead to decreases in both partners’ sleep quality. Constructive approaches to resolving conflicts is necessary for good sleep, and vice versa. Women prefer partners with sleep-wake rhythms matching their own and report higher relationship satisfactions when the couple’s chronotypes are compatible.

Conclusions

Sleep and circadian rhythms play important roles in relationships. When treating insomnia, the relationship and the partner’s sleep should be taken into account.

     

DNA methylation profiling reveals novel diagnostic biomarkers in renal cell carcinoma

Background

Renal cell carcinoma (RCC) is the tenth most commonly diagnosed cancer in the United States. While it is usually lethal when metastatic, RCC is successfully treated with surgery when tumors are confined to the kidney and have low tumor volume. Because most early stage renal tumors do not result in symptoms, there is a strong need for biomarkers that can be used to detect the presence of the cancer as well as to monitor patients during and after therapy.

Methods

We examined genome-wide DNA methylation alterations in renal cell carcinomas of diverse histologies and benign adjacent kidney tissues from 96 patients.

Results

We observed widespread methylation differences between tumors and benign adjacent tissues, particularly in immune-, G-protein coupled receptor-, and metabolism-related genes. Additionally, we identified a single panel of DNA methylation biomarkers that reliably distinguishes tumor from benign adjacent tissue in all of the most common kidney cancer histologic subtypes, and a second panel does the same specifically for clear cell renal cell carcinoma tumors. This set of biomarkers were validated independently with excellent performance characteristics in more than 1,000 tissues in The Cancer Genome Atlas clear cell, papillary, and chromophobe renal cell carcinoma datasets.

Conclusions

These DNA methylation profiles provide insights into the etiology of renal cell carcinoma and, most importantly, demonstrate clinically applicable biomarkers for use in early detection of kidney cancer.

     

Micronized palmitoylethanolamide reduces joint pain and glial cell activation

Objective and design

Temporomandibular disorder (TMD) is a common painful condition in the temporomandibular joint (TMJ). Joint inflammation is believed to be a chief cause of pain in patients with TMD, through the release of pro-inflammatory cytokines that induce peripheral sensitization of nerve terminals followed by microglial stimulation.

Materials and subject

TMJ was induced in rats with the injection of complete Freund’s adjuvant (CFA) emulsion into the left TMJ capsule.

Treatment

The present study would assess the effects of micronized palmitoylethanolamide (m-PEA) on glial activation and trigeminal hypersensitivity.

Methods

Ten mg/kg m-PEA or corresponding vehicle was administered 1 h after CFA and mechanical allodynia and edema were evaluated at 24 and 72 h after CFA injection.

Results

CFA-injected animals showed TMJ edema and ipsilateral mechanical allodynia accompanied by a robust growth in GFAP protein-positive satellite glial cells and activation of resident macrophages in the TG. Moreover, m-PEA administration significantly reduced the degree of TMJ damage and pain, macrophage activation in TG and up-regulation of Iba1.

Conclusions

The results confirm that m-PEA could represent a novel approach for monitoring pain during trigeminal nerve sensitization.

     

Picture perfect—how seeking perfection influences sleep and romantic relationships

Background

Studies have shown that sleep quality is negatively affected by perfectionism. Moreover, partner- or relationship-oriented perfectionism negatively influences relationship quality.

Objective

This paper aims to investigate the association of general perfectionism with sleep quality and relationship quality.

Materials and methods

A study assessing perfectionism, sleep quality, and relationship quality was performed via analyzing online questionnaires completed by 489 German adults from the general population.

Results

Participants with impaired sleep showed a higher level of maladaptive perfectionism (concern over mistakes and doubts, parental expectations, and criticism) than participants with good sleep, whereby the severity of sleep problems was not determining. Relationship quality is affected by perfectionism. However, this association is mediated by sleep quality.

Conclusion

Perfectionism is associated with worse sleep quality but not with worse relationship quality when sleep quality is integrated into the model as a mediator.

     

Histamine intolerance: a metabolic disease?

Objective

To evaluate the evidence regarding the disease concept of histamine intolerance as a state of inadequate histamine inactivation.

Methods

Keyword-based systematic screening of the scientific literature and of public websites focusing on diagnostic and therapeutic procedures.

Results

Histamine intolerance is commonly diagnosed based solely on subjective reporting of symptoms instead of following systematic diagnostic procedures based on objective laboratory and physical parameters. The only effective long-term therapy is avoidance of histamine-containing food.

Conclusions

The concept of histamine intolerance as a metabolic disease is in need of more experimental and clinical evidence and affected patients will benefit from a clear, evidence-based diagnostic and therapeutic regime.

     

Ontological analysis of SNOMED CT

Background

SNOMED CT is the most comprehensive medical terminology. However, its use for intelligent services based on formal reasoning is questionable.

Methods

The analysis of the structure of SNOMED CT is based on the formal top-level ontology DOLCE.

Results

The analysis revealed several ontological and knowledge-engineering errors, the most important are errors in the hierarchy (mostly from an ontological point of view, but also regarding medical aspects) and the mixing of subsumption relations with other types (mostly 'part of').

Conclusion

The found errors impede formal reasoning. The paper presents a possible way to correct these problems.

     

Antimicrobial activity of HL-60 cells compared to primary blood-derived neutrophils against <Emphasis Type="Italic">Staphylococcus aureus</Emphasis>

Background

The human leukemia cell line HL-60 is considered an alternative cell culture model to study neutrophil differentiation and migration. The aim of this study was to characterize the suitability of HL-60 cells differentiated to neutrophil-like cells (nHL-60) as substitute for blood-derived human neutrophils to investigate the interaction of neutrophils with Staphylococcus aureus.

Methods

For this purpose, antimicrobial activity, bacterial uptake, production of reactive oxygen species and the release of neutrophil extracellular traps (NETs) by nHL-60 cells were analyzed and compared to primary blood-derived neutrophils using Staphylococcus aureus as important human and animal pathogen.

Results

Overall, the antimicrobial activities of nHL-60 cells were distinctly lower compared to blood-derived neutrophils. Furthermore, production of reactive oxygen species as well as NET formation was clearly impaired in nHL-60 cells.

Conclusion

This study indicates that HL-60 cells are of limited usage as an alternative model to study antimicrobial functions of neutrophils against Staphylococcus aureus.

     

Indirubin inhibits the migration,invasion, and activation of fibroblast-like synoviocytes from rheumatoid arthritis patients

Objectives

To evaluate the inhibition of indirubin in FLSs migration, invasion, activation, and proliferation in RA FLSs.

Methods

The levels of IL-6 and IL-8 in cultural supernatants were measured by ELISA. RA FLS migration and invasion in vitro were measured by the Boyden chamber method and the scratch assay. Signal transduction protein expression was measured by western blot. FLS proliferation was detected by Edu incorporation. F-actin was measured by immunofluorescence staining.

Results

We found that indirubin reduced migration, invasion, inflammation, and proliferation in RA FLSs. In addition, we demonstrated that indirubin inhibited lamellipodium formation during cell migration. To gain insight into molecular mechanisms, we evaluated the effect of indirubin on PAK1 and MAPK activation. Our results indicated that indirubin inhibited the activity of PAK1 and MAPK.

Conclusions

Our observations suggest that indirubin may be protective against joint destruction in RA by regulating synoviocyte migration, invasion, activation, and proliferation.

     

Experimental silicosis does not aggravate collagen-induced arthritis in mice

Objectives

To investigate the effect of chronic lung inflammation on the incidence and severity of collagen-induced arthritis in mice.

Methods

Chronic lung inflammation in the form of silicosis was induced via intranasal application of silica particles. Immunization with collagen Type II commenced one week later and mice were sacrificed six weeks after booster immunization. Thereafter, silicosis was confirmed via flow cytometry and arthritis was evaluated performing knee and paw histology.

Results

Pronounced lung inflammation in the silica-treated compared to PBS-treated control mice was demonstrated by significantly elevated broncho-alveolar lavage (BAL) cell count, attributable to increased numbers of macrophages and granulocytes. Inflammation in the lungs was not associated with elevated PAD2 and PAD4 expression, yet silica treated animals had significantly higher aCCP serum titers. However, lung inflammation did not lead to an increase in the incidence of arthritis, nor did it exacerbate the macroscopic or histologic joint scores.

Conclusions

Chronic lung inflammation resulting from silicosis does not aggravate collagen-induced arthritis in mice.

     

A pathway to a stronger research culture in health policy

Background

There are currently limited pathways into a career in health policy research in Australia, due in part to a serious absence of health policy research capability in Australian universities.

Discussion

We define what we consider health policy research and education should comprise. We then examine what is currently on offer and propose ways to strengthen health policy research in Australia.

Summary

This paper, which is part analysis and part commentary, is offered to provoke wider debate about how health policy research can be nurtured in Australia.

     

Hematopoietic Stem Cell Transplantation for XIAP Deficiency in Japan

Background

X-linked inhibitor of apoptosis protein (XIAP) deficiency is a rare immunodeficiency that is characterized by recurrent hemophagocytic lymphohistiocytosis (HLH) and splenomegaly and sometimes associated with refractory inflammatory bowel disease (IBD). Although hematopoietic stem cell transplantation (HSCT) is the only curative therapy, the outcomes of HSCT for XIAP deficiency remain unsatisfactory compared with those for SLAM-associated protein deficiency and familial HLH.

Aim

To investigate the outcomes and adverse events of HSCT for patients with XIAP deficiency, a national survey was conducted.

Methods

A spreadsheet questionnaire was sent to physicians who had provided HSCT treatment for patients with XIAP deficiency in Japan.

Results

Up to the end of September 2016, 10 patients with XIAP deficiency had undergone HSCT in Japan, 9 of whom (90%) had survived. All surviving patients had received a fludarabine-based reduced intensity conditioning (RIC) regimen. Although 5 patients developed post-HSCT HLH, 4 of them survived after etoposide administration. In addition, the IBD associated with XIAP deficiency improved remarkably after HSCT in all affected cases.

Conclusion

The RIC regimen and HLH control might be important factors for successful HSCT outcomes, with improved IBD, in patients with XIAP deficiency.