Informal out-of-pocket payments experience and individuals’ willingness-to-pay for healthcare services in Greece

BackgroundInformal out-of-pocket payments to healthcare providers are not uncommon in the Greek health system. We explore individuals’ willingness-to-pay (WTP) to secure zero out-of-pocket full coverage for healthcare services and medications and we estimate the impact of past informal payments and individuals’ opinion about the legalization of informal payments on WTP.MethodsWe conducted a survey of 2841 participants from November 2016 to February 2017. We obtained information on WTP using the contingent valuation method. A two-part regression model was used to estimate the association between WTP, informal payments, and respondents’ opinion about legalizing such payments.ResultsAbout 80% of the respondents were willing to pay an average of €95 per month to obtain free access to full healthcare coverage and medications. About 65% of the respondents were involved in an informal payment at least once during the past four months with an average payment of €247. Higher informal payments and supportive opinions towards the legalization of informal payments increased the likelihood of WTP and were also positively associated with increased WTP amounts overall (p < 0.001).ConclusionsThis survey reveals that individuals’ WTP is critically affected by previous experiences and attitudes towards informal payments. Our results imply that the potential introduction of official fees might not suffice to limit informal payments and suggest the need for stricter regulatory policies.     

Breast Disorders in Adolescence: A Review of the Literature

BackgroundAdolescence is accompanied by a variety of changes in young breast development, which greatly affects the adolescent''s psychology and socialization.SummaryPubMed, EMBASE, and the Cochrane Library were searched for studies relative to epidemiology, clinical characteristics, diagnosis, and management of all breast disorders in adolescence and their consequences. Development disorders are breast asymmetry, breast atrophy, breast hypoplasia, hypomastia, juvenile breast hypertrophy, and tuberous breast. Breast congenital abnormalities include athelia, amastia, accessory breast tissue, polymastia, polythelia, and congenital disorders of nipples. Breast infections are commonly caused from Gram-positive coccus rather than Gram-negative bacteria. Breast abscess occurs when breast infections are not promptly treated. Nipple discharge is caused by a variety of conditions and should be managed carefully. Fibrocystic changes, cysts, and fibroadenomas are the most common benign masses in adolescence. Primary, secondary, or metastatic breast cancer is extremely rare in adolescence. However, clinicians should include breast cancer in the differential diagnosis of a breast mass in adolescence.Key MessagesClinicians should be aware of all breast disorders that may occur in adolescence. Early diagnosis and treatment will result in the reassurance of adolescents and their families without any detrimental effect on their psychology, sexual behavior, and socialization. Adolescents with breast disorders may require a multidisciplinary approach by a pediatrician, a gynecologist specializing in pediatric-adolescent gynecology, a plastic surgeon, and a psychologist for the best management of breast disorders.     

Synovial fluid as an alternative specimen for quantification of drugs of abuse by GC–MS

Forensic Toxicology -     

Prognostic value of preoperative dynamic contrast-enhanced MRI perfusion parameters for high-grade glioma patients

Introduction

The prognostic value of the dynamic contrast-enhanced (DCE) MRI perfusion and its histogram analysis-derived metrics is not well established for high-grade glioma (HGG) patients. The aim of this prospective study was to investigate DCE perfusion transfer coefficient (K^trans), vascular plasma volume fraction (v_p), extracellular volume fraction (v_e), reverse transfer constant (k_ep), and initial area under gadolinium concentration time curve (IAUGC) as predictors of progression-free (PFS) and overall survival (OS) in HGG patients.

Methods

Sixty-nine patients with suspected anaplastic astrocytoma or glioblastoma underwent preoperative DCE-MRI scans. DCE perfusion whole tumor region histogram parameters, clinical details, and PFS and OS data were obtained. Univariate, multivariate, and Kaplan–Meier survival analyses were conducted. Receiver operating characteristic (ROC) curve analysis was employed to identify perfusion parameters with the best differentiation performance.

Results

On univariate analysis, v_e and skewness of v_p had significant negative impacts, while k_ep had significant positive impact on OS (P < 0.05). v_e was also a negative predictor of PFS (P < 0.05). Patients with lower v_e and IAUGC had longer median PFS and OS on Kaplan–Meier analysis (P < 0.05). K^trans and v_e could also differentiate grade III from IV gliomas (area under the curve 0.819 and 0.791, respectively).

Conclusions

High v_e is a consistent predictor of worse PFS and OS in HGG glioma patients. v_p skewness and k_ep are also predictive for OS. K^trans and v_e demonstrated the best diagnostic performance for differentiating grade III from IV gliomas.

     

Initiation Codon Scanthrough versus Termination Codon Readthrough Demonstrates Strong Potential for Major Histocompatibility Complex Class I–restricted Cryptic Epitope Expression

Accumulating evidence shows that the repertoire of major histocompatibility complex class I–restricted epitopes extends beyond conventional translation reading frames. Previously, we reported that scanthrough translation, where the initiating AUG of a primary open reading frame is bypassed, is most likely to account for the presentation of cryptic epitopes from alternative reading frames within the influenza A PR/8/34 nucleoprotein gene. Here, we confirm and extend these findings using an epitope cassette construct that features two well-defined CD8⁺ T cell (T_CD8+) epitopes in alternative reading frames, each preceded by a single start codon. Expression of one epitope depends on scanning of the ribosome over the first AUG with translation initiation occurring at the second AUG. We find that scanthrough translation has great potency in our system, with its impact being modulated, as predicted, by the base composition surrounding the first initiation codon, the number of start codons preceding the point of alternate reading frame initiation, and the efficiency with which the epitope itself is generated. Additionally, we investigated the efficiency of eukaryotic translation termination codons, to assess codon readthrough as a mechanism for cryptic epitope expression from 3′ untranslated regions. In contrast with initiation codons, eukaryotic stop codons appear to be highly efficient at preventing expression of epitopes encoded in 3′ untranslated regions, suggesting that 3′ untranslated regions are not a common source of cryptic epitope substrate. We conclude that scanthrough is a powerful mechanism for the expression of epitopes encoded in upstream alternative open reading frames that may contribute significantly to T_CD8+ responses and to tolerance induction.T_CD8+ activation depends upon interaction between the clonotypic TCR and a MHC class I molecule complexed with an 8–10 amino acid peptide epitope (1–5). Conventional models of antigen processing and presentation generally presume these epitopes to be derived from the cytosolic proteolysis of full-length, fully translated proteins. However, it has been demonstrated that T_CD8+ are also capable of recognizing either the products of gene fragments or mini genes expressing the minimal sequence of an epitope (6–8). In addition, there is sufficient evidence in the literature to suggest that strict adherence to conventional translation is not required for antigen presentation. Examples include the presentation of epitopes encoded in untranslated regions (UTRs)¹ (9, 10) and in alternative reading frames (RF) (11–15). This implies that regions of genes that are traditionally thought to be inaccessible to translation could be a potentially significant source of substrate for antigen processing and presentation.The generally accepted model for translation initiation of most messages is the ribosomal scanning hypothesis (16– 18), where a ribosome scans from the 5′-cap and begins translation from the first AUG in favorable context, as determined by surrounding nucleotide identity. This AUG defines the primary RF, or RF0. Extensive surveys of eukaryotic genes have shown that in most cases the first AUG encountered is in favorable context (19, 20) and biochemical studies have shown that a primary start codon is used by the great majority of scanning ribosomes (21). However, some ribosomes fail to initiate at the primary initiation codon, with factors such as proximity to the 5′-cap, and local secondary structures as well as initiation codon context having influence (22, 23). We have recently demonstrated that initiation codon readthrough (scanthrough) is probably responsible for the production of epitopes encoded in alternative RFs from a mutated influenza A PR/8/34 nucleoprotein (NP) gene (24). In the system studied, it appeared that scanthrough was capable of utilizing an internal AUG codon to rescue the presentation of three NP epitopes (NP_50–57, NP_147–155, NP_366–374) that had been shifted out-of-frame by a base deletion in the second codon of the NP open reading frame (ORF). In addition to providing this alternative source of out-of-frame epitopes, scanthrough translation may simultaneously produce truncated, in-frame polypeptides that could be more efficiently processed than full-length protein by the class I processing machinery. This mechanism could also provide a plausible rationale for the presentation of exocytic proteins that do not normally access the cytosolic protein-degradation apparatus, by allowing initiation of translation after the signal sequence encoding region, resulting in the production of a nontranslocated substrate.As in the case of start codons, not all translation stop codons cause termination of translation with equal efficiency. The sequence surrounding the termination codon dictates whether some readthrough and continued translation can occur. In Saccharomyces cerevisiae, termination codon readthrough has been shown to occur at levels up to 3.35% (25). This mechanism would allow for translation from the 3′ UTR, further expanding the available substrate for class I presentation.In the current study, we have constructed a presentation cassette in order to assess the potential for ribosomal scanthrough in epitope expression under controlled conditions. This allowed us, first, to confirm our previous findings concerning initiation codon readthrough and, second, to assess directly the strength of initiation codon readthrough in the face of competitive AUG codons encoded in alternate RFs. In addition, we wished to discern whether epitopes encoded in 3′ UTR are also available for presentation. For this purpose, we tested the ability of ribosomes to read through strong and weak RF0 stop signals inserted in wild-type NP and translate a downstream epitope. These studies provide important insights into the translation mechanisms available for the production of substrate from unconventional coding regions.     

Piriformis muscle syndrome: A cross-sectional imaging study in 116 patients and evaluation of therapeutic outcome

Objectives

To increase the clinical awareness of piriformis muscle syndrome (PMs) by reporting cross-sectional imaging findings, the clinical impact of imaging studies and treatment outcome.

Methods

Within a 10-year-period, 116 patients referred for radiological evaluation of clinically suspected PMs, with excluded lumbar pathology related to symptomatology, were prospectively studied with MRI and/or computed tomography (CT). Piriformis muscle (PM), sciatic nerve (SN), piriformis region and sacroiliac joints were evaluated. PMs was categorised into primary/secondary, according to a reported classification system. Treatment decisions were recorded. Outcome was categorised using a 3-point-scale.

Results

Seventy-four patients (63.8%) exhibited pathologies related to PMs. Primary causes were detected in 12 and secondary in 62 patients. PM enlargement was found in 45.9% of patients, abnormal PM signal intensity/density in 40.5% and sciatic neuritis in 25.7%. Space-occupying lesions represented the most common related pathology. Treatment proved effective in 5/8 patients with primary and 34/51 patients with secondary PMs. In 34 patients, imaging revealed an unknown underlying medical condition and altered treatment planning.

Conclusions

Secondary PMs aetiologies appear to prevail. In suspected PMs, PM enlargement represented the most common imaging finding and space-occupying lesions the leading cause. Imaging had the potential to alter treatment decisions.

Key Points

? In clinically suspected PMs cross-sectional imaging may reveal variable pathology. ? Secondary PMs aetiologies appeared to be more common than primary. ? PM enlargement represented the most common imaging finding in clinically suspected PMs. ? Space-occupying lesions in the piriformis region represented the leading cause of PMs. ? In clinically suspected PMs cross-sectional imaging may alter treatment planning.

     

Distribution of CD1A-positive langerhans cells and lymphocyte subsets in transitional cell carcinoma of the urinary bladder. An immunohistological study on frozen sections

The distribution of CD1a-positive Langerhans cells, CD4-positive T-helper cells, and CD8-positive T-suppressor cells in 36 patients with transitional cell carcinoma of the urinary bladder was studied immunohistochemically on frozen sections. Multiple tissue specimens from the tumour, the adjacent mucosa, and random bladder wall biopsies were examined. Langerhans cells were mainly interspersed among the tumour cells, whereas T-helper cells were present in aggregates in the stroma. T-suppressor cells were present both in aggregates in the stroma and among the tumour cells. There was a marginal relationship between the density of Langerhans cells and the density of T-helper/inducer cells and a good relationship with CD8-positive cells. There was no statistically significant difference in the population density of Langerhans cells associated with the various clinicopathological variables, including growth pattern, histological grade and stage, or patient's age and sex. On the contrary, a statistically significant difference was found in the CD1a/CD4 ratio among specimens of different grades. These results show that CD1a cell populations correlate with T-cell populations in bladder cancer, suggesting that Langerhans cells take part in the immune response carried out by T lymphocytes, their task being apparently antigen presentation.