Molecular Biomarkers Detected Using Fluorescence in situ Hybridization in a Filipino with Retinoblastoma.

Background and Objective: Retinoblastoma is one of the most common intraocular cancers among children usually caused by the loss of retinoblastoma protein function. Despite being a highly heritable disease, conventional diagnostic and prognostic methods depend on clinical examination, with limited consideration of cancer genetics in the standard of care. CD133, KRT19, and MUC1 are commonly explored genes for their utility in liquid biopsies of cancer including lung adenocarcinoma. To date, there are few extensive molecular studies on retinoblastoma in Filipino patients. To this end, the study aimed to describe the copy number of CD133, KRT19, and MUC1 in retinoblastoma samples from a Filipino patient and quantitate the respective expression level of these genes. Methods: Hematoxylin & Eosin (H&E) staining was utilized to characterize the retinoblastoma tissue while fluorescence in situ hybridization (FISH) using probes specific to CD133, KRT19, and MUC1 was performed to determine the copy number of genes in retinoblastoma samples from a Filipino patient (n = 1). The gene expression of CD133, MUC1, and KRT19 was quantitated using RT-qPCR. Results: The H&E staining in the retinoblastoma tissue shows poorly differentiated cells with prominent basophilic nuclei. CD133 was approximately 1.5-fold overexpressed in the retinoblastoma tissue with respect to the normal tissue, while MUC1 and KRT19 are only slightly expressed. Multiple intense signals of each probe were localized in the same nuclear areas throughout the retinoblastoma tissue, with high background noise. Conclusion: These findings suggest that CD133 is a potential biomarker for the staging and diagnosis of retinoblastoma in Filipino cancer patients. However, further optimization of the hybridization procedures is recommended.

When comprehension elicits incomprehension: Deterioration of semantic categorisation in the absence of stimulus repetition.

Repetition improves retrieval from memory; however, under some circumstances, it can also impair performance. Separate literatures have investigated this phenomenon, including studies showing subjective loss of meaning following 'semantic satiation', slowed naming and categorisation when semantically related items are repeated and semantic 'access deficits' in aphasia. Such effects have been variously explained in terms of habituation of repeatedly accessed representations, increased interference from strongly activated competitors and long-term weight changes reflecting the suppression of non-targets on earlier trials (i.e., retrieval-induced forgetting). While studies of semantic satiation involve massed repetition of individual items, competition and weight changes at the conceptual level should elicit declining comprehension for non-repeated items: this pattern has been demonstrated for picture naming but effects in categorisation are less clear. We developed a paced serial semantic task (PSST), in which participants identified category members among distracters. Performance in healthy young adults deteriorated with ongoing retrieval for non-repeated words belonging to functional categories (e.g., picnic), taxonomic categories (e.g., animal) and feature-based categories (e.g., colour red - 'tomato', 'post box'). This decline was greatest at fast presentation speeds (when there was less time to overcome competition/inhibition) and for strongly associated targets (which may have accrued more inhibition to facilitate earlier target categorisation). Deteriorating performance was also seen across words and pictures, consistent with a conceptual locus. We observed a release from deteriorating categorisation following a switch to a new category, demonstrating that this was not a general effect of time on task. Patients with semantic aphasia, who have deficient semantic control, maintained their performance throughout the categories, unlike younger adults: this finding is hard to reconcile with accounts of declining performance that propose a build-up of competition, since the patients should have had greater difficulty resolving such competition. These results instead suggest that declining performance on our goal-driven categorisation task was linked to the use of a controlled retrieval strategy by healthy young adults. Patients may not have inhibited related non-target knowledge to facilitate initial categorisation like younger volunteers, and consequently they were less vulnerable to declining comprehension in this paradigm. Together, these results demonstrate circumstances which produce declines in continuous categorisation in healthy adults.

An unusual case of cavitating pulmonary nodules: Lemierre's syndrome with isolated involvement of the external jugular vein.

A 65-year-old female presented with symptoms of tonsillitis and sepsis. Despite initial treatment with i.v. fluid and antibiotics, her condition deteriorated and she became hypoxaemic. CT pulmonary angiography showed no filling defects in the pulmonary arteries, but there were multiple cavitating lung nodules, initially thought to represent metastases. A subsequent contrast-enhanced CT of the neck and thorax demonstrated thrombosis of the left external jugular vein (EJV), leading to a revised diagnosis of Lemierre's syndrome (i.e. septic embolization from jugular thrombophlebitis). Noteworthy aspects of the case include the initial misdiagnosis of the cavitating lung nodules by the reporting radiologist and the isolated involvement of the EJV-Lemierre's syndrome usually involves the internal jugular vein. The case highlights the importance of septic emboli in the differential diagnosis of cavitating lung nodules, and of assessment of the EJV as well as internal jugular vein in the context of oropharyngeal infection.

Keeping it together: Semantic coherence stabilizes phonological sequences in short-term memory.

Our ability to hold a sequence of speech sounds in mind, in the correct configuration, supports many aspects of communication, but the contribution of conceptual information to this basic phonological capacity remains controversial. Previous research has shown modest and inconsistent benefits of meaning on phonological stability in short-term memory, but these studies were based on sets of unrelated words. Using a novel design, we examined the immediate recall of sentence-like sequences with coherent meaning, alongside both standard word lists and mixed lists containing words and nonwords. We found, and replicated, substantial effects of coherent meaning on phoneme-level accuracy: The phonemes of both words and nonwords within conceptually coherent sequences were more likely to be produced together and in the correct order. Since nonwords do not exist as items in long-term memory, the semantic enhancement of phoneme-level recall for both item types cannot be explained by a lexically based item reconstruction process employed at the point of retrieval ("redintegration"). Instead, our data show, for naturalistic input, that when meaning emerges from the combination of words, the phonological traces that support language are reinforced by a semantic-binding process that has been largely overlooked by past short-term memory research.