Olfactory capacity declines with aging, but increasing evidence shows that smell dysfunction is one of the early signs of prodromal neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. The study of olfactory ability and its role in neurodegenerative diseases arouses much interest in the scientific community. In neurology, olfactory impairment is a potential early marker for the onset of neurodegenerative diseases, but the underlying mechanism is poorly understood. The loss of smell is considered a clinical sign of early-stage disease and a marker of the disease’s progression and cognitive impairment. Highlighting the importance of biological bases of smell and molecular pathways could be fundamental to improve neuroprotective and therapeutic strategies. We focused on the review articles and meta-analyses on olfactory and cognitive impairment. We depicted the neurobiology of olfaction and the most common olfactory tests in neurodegenerative diseases. In addition, we underlined the close relationship between the olfactory and cognitive deficit due to nasal neuroepithelium, which is a direct extension of the CNS in communication with the external environment. Neurons, Nose, and Neurodegenerative diseases highlights the role of olfactory dysfunction as a clinical marker for early stages of neurodegenerative diseases when it is associated with molecular, clinical, and neuropathological correlations.

Background: Oral squamous cell carcinoma (OSCC) is one of the most frequent cancers worldwide. Endoscopic methods may be useful in the evaluation of oral injuries even though the diagnostic gold standard is a biopsy. Targeted screenings could be considered the best way to prevent the occurrence of oral cancer. Aimed to elucidate the potential identification of specific biomarkers of OSCC, the use of saliva is convenient and noninvasive. Many studies reported more than a hundred putative saliva biomarkers for OSCC, and proteogenomic approaches were fundamental to disclosing this issue. Methods: Relevant literature published in the last few years was systematically searched on PubMed and we focused on articles about the use and study of salivary biomarkers in the diagnostics of head and neck cancer (n = 110). Thereafter, we performed a selection focusing on diagnosis with salivary proteomics in OSCC (n = 8). Results: Saliva proteomics can be a source of biomarkers for OSCC. We reviewed literature of biomarker proteins in saliva that could also be evaluated as probable targets for non-invasive screening of oral neoplasm such as cytokines, matrix metalloproteinases, and acute-phase response proteins. Conclusions: The measurement of salivary biomarkers is a highly hopeful technique for the diagnosis of OSCC. Proteogenomic approaches could permit an accurate and early diagnosis of OSCC. This review seeks to generate an up-to-date view on translational OSCC issues by raising awareness of researchers, physicians, and surgeons. Renewed clinical studies, which will validate the sensitivity and specificity of salivary biomarkers, are necessary to translate these results into possible strategies for early diagnosis of OSCC, thus improving patient outcomes.

Background: Anosmia is defined as the complete absence of olfactory function, which can be caused by a variety of causes, with upper respiratory tract infections being among the most frequent causes. Anosmia due to SARS-CoV-2 infection has attracted attention given its main role in symptomatology and the social impact of the pandemic. Methods: We conducted systematic research in a clinicaltrials.gov database to evaluate all active clinical trials worldwide regarding drug therapies in adult patients for anosmia following SARS-CoV-2 infection with the intention of identifying the nearby prospects to treat Anosmia. We use the following search terms: “Anosmia” AND “COVID-19” OR “SARS-CoV-2” OR “2019 novel coronavirus”. Results: We found 18 active clinical trials that met our criteria: one phase 1, one phase 1–2, five phases 2, two phases 2–3, three phases 3, and six phases 4 studies were identified. The drug therapies that appear more effective and promising are PEA-LUT and Cerebrolysin. The other interesting drugs are 13-cis-retinoic acid plus aerosolized Vitamin D, dexamethasone, and corticosteroid nasal irrigation. Conclusions: COVID-19 has allowed us to highlight how much anosmia is an important and debilitating symptom for patients and, above all, to direct research to find a therapy aimed at curing the symptom, whether it derives from SARS-CoV-2 infection or other infections of the upper airways. Some of these therapies are very promising and are almost at the end of experimentation. They also provide hope in this field, which not addressed until recently.

Background: Bacteria colonizing the nasal cavity contribute to mucosal homeostasis, and altered sinonasal bacterial communities have been associated with chronic rhinosinusitis with nasal polyps (CRSwNP). Whether routine, culture-based microbiology can distinguish the cultivable bacterial profile of CRSwNP patients from that of controls remains unclear. Methods: In this single-center observational pilot study, middle-meatus swabs from 30 patients with CRSwNP and 30 controls were cultured on four media, and isolates were identified with the VITEK 2 system. For each species, presence or absence per subject was compared between groups using Fisher’s exact test with Benjamini–Hochberg correction for multiple comparisons; the number of cultivable species per subject was compared with the Mann–Whitney test. Results: The two groups were comparable in age and sex. Patients yielded more cultivable bacterial species per subject than controls (mean 4.4 vs. 2.9; Mann–Whitney p < 0.001). Several species were numerically more frequent in patients (e.g., Staphylococcus hominis, S. lugdunensis) and others in controls (e.g., S. epidermidis, S. aureus), but no individual species difference remained significant after correction. Conclusions: Using routine culture, CRSwNP was characterized chiefly by a higher number of cultivable bacterial species, whereas individual species differences were not statistically robust. These hypothesis-generating findings warrant confirmation in larger, sequencing-based studies.

Deep-Brain Stimulation (DBS) is an important treatment option for the management of Parkinson’s disease (PD) and is a common symptomatic treatment. However, an increasing number of studies have examined the biological processes to assess if DBS can also modify the natural history of PD by acting on its pathophysiological mechanisms. Relevant literature published up to November 2020 was systematically searched on databases such as PubMed, ISI Web of Knowledge, Academic Search Index, and Science Citation Index. The following predefined inclusion criteria were applied to the full-text versions of the selected articles: i) recruiting and monitoring of PD subjects that were previously treated with DBS and ii) investigating the electrophysiological, biochemical, epigenetic, or neuroimaging effects of DBS. Studies focusing exclusively on motor and clinical changes were excluded. Reviews, case reports, studies on animal models, and computational studies were also not considered. Out of 2,960 records screened, 43 studies met the inclusion criteria. Only three studies described a potential disease-modifying effect of DBS. However, a wide heterogeneity was observed in the investigated biomarkers, and the design and methodological issues of several studies limited their ability to find potential disease-modifying features. Specifically, 60.4% of the trials followed-up subjects for no more than 1 year from the surgical intervention, and 67.4% observed patients with PD only once after DBS. Moreover, 64.2% of the studies enrolled late-stage PD patients. Most of the studies (88.4%) reported that DBS only had a symptomatic effect, with several of them showing some limitations in the study design and recruitment of patients. Further studies using shared biomarkers are encouraged to assess if and how DBS might affect the progression of PD. Based on the existing preclinical literature, prospective clinical trials examining the course of PD in early-stage patients are needed.

Liquid biopsy, the analysis of tumor-derived material in blood, saliva, and other body fluids, is increasingly explored for the diagnosis, surveillance, and molecular characterization of head and neck squamous cell carcinoma (HNSCC). Its performance, however, is not uniform across the disease, and the reason is fundamentally molecular. human papillomavirus (HPV)-positive oropharyngeal cancers carry viral oncogenes that are absent from the host genome and therefore provide a near ideal, tumor specific circulating marker, whereas HPV-negative tumors are driven by a heterogeneous somatic landscape that offers no single universal target. In this narrative review, we adopt a molecular perspective. We first examine the biological origin of circulating tumor DNA and of the other analytes that liquid biopsy can interrogate including circulating tumor HPV DNA, viral transcripts, microRNAs, extracellular vesicles, and methylation signatures. We then consider how analytical platforms, from droplet digital PCR to next generation and ultrasensitive whole-genome sequencing, translate these molecules into measurements. Only afterward do we discuss the clinical questions, organized by clinical objective rather than by individual study: diagnosis and early detection, prognosis and risk stratification, treatment response monitoring, minimal residual disease and surveillance, and biomarker guided de-escalation in HPV-positive disease. Twelve registered clinical trials, involving approximately 1183 patients, are presented as illustrations of these questions. We close on the biological and technical gaps that still separate promising signals from clinical practice, and on the multi analyte and dynamic strategies most likely to bridge them. At present, liquid biopsy should be regarded as a complementary tool rather than as a replacement for established clinicopathological assessment.