The grade of systemic inflammation, immune inhibition, and gut dysbiosis as prognostic factors for bladder cancer recurrence: a metabolomics approach.

BACKGROUND: The risk of recurrence for non-muscle invasive bladder cancer (NMIBC) is high, and the current methods of predicting it rely on clinical and histopathological markers. Personalized risk assessment can be improved by including new prognostic biomarkers. Our research explores the potential of urinary metabolomics to predict cancer recurrence in NMIBC patients within three years. METHODS: Fifty NMIBC patients were included in the study. Urine samples were collected at diagnosis and before TUR-BT. After three years, patients were classified as relapsed or non-relapsed. An NMR-based metabolomics approach was used to measure the concentration of 44 metabolites in the urine of these patients at the time of their diagnosis. This method provides a comprehensive view of many urinary compounds potentially valuable for discriminating relapsing from non-relapsing patients. The measured metabolic profiles were analyzed through multivariate analysis, probability ROC curves, and Mann-Whitney tests. RESULTS: Seven metabolites were involved in NMIBC recurrence prediction. We interpret their alteration as the consequence of three main events: gut dysbiosis, systemic inflammation, and immune inhibition. Since these compounds have already been proposed for BC diagnosis, what distinguishes their role as prognostic or diagnostic is the grade of their alteration. Limitations: small sample size; further research to confirm urinary compounds' correlation with physiological processes. CONCLUSIONS: This study exploits urinary metabolic profiles to predict NMIBC recurrence. Specific metabolites are found to be significantly related to cancer relapse. The study highlights the grade of inflammation, immune suppression, and gut dysbiosis in predicting cancer recurrence.

Characterization and Clinical Assessment of a Peculiar Case of Hemolytic Anemia.

Thalassemic diseases are characterized by a reduced (ß+) or absent (ß0) synthesis of the globin chains of hemoglobin (Hb) due to genetic mutations. ß-thalassemia was more frequent in the Mediterranean area, but now it is diffused worldwide. Three possible genetic forms can be distinguished: ß0/ß0, the most severe (Cooley's disease); ß0/ß+ of intermediate severity; ß+/ß+ associated with ß-thalassemia intermedia or minor. Recently, a clinical non-genetic classification has been proposed: transfusion-dependent thalassemia (TDT), requiring regular lifetime blood transfusions, and non-transfusion-dependent thalassemia (NTDT), requiring occasional transfusions to manage acute cases. In this report, we studied a patient whose blood count indicated a severe anemia but also showed thrombocytosis, leukocytosis, and an elevated number of nucleated red blood cells (NRBC). These altered blood parameters suggested initially a possible diagnosis of hemoglobinopathy or myeloproliferative syndrome. The molecular and genetic analyses demonstrated the presence of HbF (5.3%) and HbA2 (7.7%) and the presence of the homozygote mutation (IVS1.6T>C) in the ß-globin gene. According to these data, a diagnosis of ß-thalassemia intermedia form has been proposed. Nevertheless, the clinical condition, the presence of thrombocytosis, leukocytosis, an elevated number of NRBC, and the frequent blood transfusions lead to reclassification of the patient as TDT subject. Consequently, this result suggests that a unique genotype-phenotype correlation is not possible in the presence of ß+mutations since other concomitant pathologies can exacerbate the disease.

Comparable antibody levels in heterologous and homologous mRNA COVID-19 vaccination, with superior neutralizing and IgA antibody responses in mRNA homologous boosting.

BACKGROUND: Priming with two doses of AZD1222 (Oxford-AstraZeneca; ChAd) followed by a third mRNA vaccine boosting is considered in several countries, yet comparisons between heterologous and homologous booster efficacy remain unexplored. AIM: To evaluate and contrast the immunogenicity of homologous and heterologous boosting regimens. METHOD: The study examined antibody responses in 1113 subjects, comprising 895 vaccine-naïve individuals across different vaccination strategies (partial, primary series, heterologous booster, homologous booster) and 218 unvaccinated, naturally infected individuals. Assessments included neutralizing total antibodies (NTAbs), total antibodies (TAbs), anti-S-RBD IgG, and anti-S1 IgA levels. RESULTS: The study found mRNA vaccines to exhibit superior immunogenicity in primary series vaccination compared to ChAd, with mRNA-1273 significantly enhancing NTAbs, TAbs, anti-S-RBD IgG, and anti-S1 IgA levels (p < 0.001). Both booster types improved antibody levels beyond primary outcomes, with no significant difference in TAbs and anti-S-RBD IgG levels between regimens. However, homologous mRNA boosters significantly outperformed heterologous boosters in enhancing NTAbs and anti-S1 IgA levels, with the BNT/BNT/BNT regimen yielding particularly higher enhancements (p < 0.05). CONCLUSION: The study concludes that although TAbs and anti-S-RBD IgG antibody levels are similar for both regimens, homologous mRNA boosting outperform heterologous regimen by enhancing anti-S1 IgA and neutralizing antibody levels.

Vitamin D Deficiency in Professional Football Players during Competitive Season of Italian First Division (Serie A).

BACKGROUND: Data in the literature have demonstrated the crucial role that vitamin D plays in the human organism, and recent studies also emphasize this essential role of vitamin D in athletes. Indeed, vitamin D acts on the skeletal muscles and plays a fundamental role in numerous physiological processes involved in immune function. Many factors such as sun exposure, skin tone, body mass index and chronic illness affect vitamin D levels. The aim of the study is to evaluate vitamin D levels in professional football players in Italy and investigate the variations in vitamin D values in footballers who train at different latitudes. METHODS: The study performed is a retrospective observational study analyzing 25-OH vitamin D values in professional football players of the Italian First Division (Serie A). Two teams during the competitive season were selected: team A (latitude of 41° N in southern Italy) and team B (latitude of 45° N in northern Italy). Three time periods were identified and were classified as follows: the first quarter (May, June, July, and August), the second quarter (September, October, November, and December) and the third quarter (January, February, March, and April). The purpose of this was to study the average values of vitamin D during the year corresponding to different levels of sunlight exposure. Each athlete was subjected to at least one sampling during the three quarters of the competitive season. RESULTS: Both vitamin D insufficiency (10.1%) and overt deficiency (1.93%) were found in Italian Serie A players. Insufficient vitamin D values are between 20 ng/mL and 29 ng/mL and overt deficiency values <20 ng/mL. At the same time, the data demonstrated a significant variation in vitamin D values depending on the period of the competitive season and the latitude of the cities of the two teams. In detail, there was no significant difference in the first quarter, while there was a significant increase in vitamin D values in team B in the second and third quarter, at p < 0.01 and p < 0.05, respectively. CONCLUSIONS: Latitude and seasons have a significant impact on vitamin D levels. Therefore, it is essential to measure vitamin D in professional football players, especially during the spring and winter months, so as to monitor changes in levels in relation to the season and latitude and evaluate any supplements. Further studies should be performed to evaluate the relationship between vitamin D deficiency and football players' athletic performance.

Follow-Up and Comparative Assessment of SARS-CoV-2 IgA, IgG, Neutralizing, and Total Antibody Responses After BNT162b2 or mRNA-1273 Heterologous Booster Vaccination.

BACKGROUND: Priming with ChAdOx1 followed by heterologous boosting is considered in several countries. Nevertheless, analyses comparing the immunogenicity of heterologous booster to homologous primary vaccination regimens and natural infection are lacking. In this study, we aimed to conduct a comparative assessment of the immunogenicity between homologous primary vaccination regimens and heterologous prime-boost vaccination using BNT162b2 or mRNA-1273. METHODS: We matched vaccinated naïve (VN) individuals (n = 673) with partial vaccination (n = 64), primary vaccination (n = 590), and primary series plus mRNA vaccine heterologous booster (n = 19) with unvaccinated naturally infected (NI) individuals with a documented primary SARS-CoV-2 infection (n = 206). We measured the levels of neutralizing total antibodies (NTAbs), total antibodies (TAbs), anti-S-RBD IgG, and anti-S1 IgA titers. RESULTS: Homologous primary vaccination with ChAdOx1 not only showed less potent NTAb, TAb, anti-S-RBD IgG, and anti-S1 IgA immune responses compared to primary BNT162b2 or mRNA-1273 vaccination regimens (p < 0.05) but also showed ~3-fold less anti-S1 IgA response compared to infection-induced immunity (p < 0.001). Nevertheless, a heterologous booster led to an increase of ~12 times in the immune response when compared to two consecutive homologous ChAdOx1 immunizations. Furthermore, correlation analyses revealed that both anti-S-RBD IgG and anti-S1 IgA significantly contributed to virus neutralization among NI individuals, particularly in symptomatic and pauci-symptomatic individuals, whereas among VN individuals, anti-S-RBD IgG was the main contributor to virus neutralization. CONCLUSION: The results emphasize the potential benefit of using heterologous mRNA boosters to increase antibody levels and neutralizing capacity particularly in patients who received primary vaccination with ChAdOx1.

Laboratory Diagnosis of Intrathecal Synthesis of Immunoglobulins: A Review about the Contribution of OCBs and K-index.

The diagnosis of MS relies on a combination of imaging, clinical examinations, and biological analyses, including blood and cerebrospinal fluid (CSF) assessments. G-Oligoclonal bands (OCBs) are considered a "gold standard" for MS diagnosis due to their high sensitivity and specificity. Recent advancements have involved the introduced of kappa free light chain (k-FLC) assay into cerebrospinal fluid (CSF) and serum (S), along with the albumin quotient, leading to the development of a novel biomarker known as the "K-index" or "k-FLC index". The use of the K-index has been recommended to decrease costs, increase laboratory efficiency, and to skip potential subjective operator-dependent risk that could happen during the identification of OCBs profiles. This review aims to provide a comprehensive overview and analysis of recent scientific articles, focusing on updated methods for MS diagnosis with an emphasis on the utility of the K-index. Numerous studies indicate that the K-index demonstrates high sensitivity and specificity, often comparable to or surpassing the diagnostic accuracy of OCBs evaluation. The integration of the measure of the K-index with OCBs assessment emerges as a more precise method for MS diagnosis. This combined approach not only enhances diagnostic accuracy, but also offers a more efficient and cost-effective alternative.

Potential Anti-Inflammatory and Anti-Fatigue Effects of an Oral Food Supplement in Long COVID Patients.

Long coronavirus disease (COVID) syndrome leads to chronic inflammatory state onset that can have a multisystem impact and compromise organ function. Moreover, long COVID syndrome is often characterized by the presence of chronic fatigue, which affects subjects' daily activities and worsens their quality of life. The aim of our double-blind, placebo-controlled randomized trial (protocol code RS 150.21, approved on 4 November 2021) was to evaluate the beneficial effects of the consumption of 2 cps/day, for two months, of an oral food supplement (OFS), based on Echinacea angustifolia, rosehip, propolis, royal jelly and zinc, in long COVID patients, compared to a two-month placebo period. The OFS's vitamin C content was equal to 22.17 mg/g (8.87 mg/capsule). The OFS's total polyphenol content was 43.98 mg/g gallic acid equivalents. At the end of the in vivo study, we highlighted a significant decrease in the inflammatory parameters in the OFS period, compared to the placebo period (neutrophil-to-lymphocyte ratio, p = 0.0455; monocyte to-lymphocyte ratio, p = 0.0005; C-reactive protein, p = 0.0145). Our study also highlighted a significant increase in vitamin D serum values (p = 0.0005) and, at the same time, an improvement in patients' life quality and a reduction in fatigue, monitored by the fatigue severity scale. This study showed the OFS's beneficial effects on the inflammatory state, fatigue and quality of life in long COVID patients.

SARS-CoV-2 infection triggers more potent antibody-dependent cellular cytotoxicity (ADCC) responses than mRNA-, vector-, and inactivated virus-based COVID-19 vaccines.

Neutralizing antibodies (NAbs) are elicited after infection and vaccination and have been well studied. However, their antibody-dependent cellular cytotoxicity (ADCC) functionality is still poorly characterized. Here, we investigated ADCC activity in convalescent sera from infected patients with wild-type (WT) severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) or omicron variant compared with three coronavirus disease 2019 (COVID-19) vaccine platforms and postvaccination breakthrough infection (BTI). We analyzed ADCC activity targeting SARS-CoV-2 spike (S) and nucleocapsid (N) proteins in convalescent sera following WT SARS-CoV-2-infection (n = 91), including symptomatic and asymptomatic infections, omicron-infection (n = 8), COVID-19 vaccination with messenger RNA- (mRNA)- (BNT162b2 or mRNA-1273, n = 77), adenovirus vector- (n = 41), and inactivated virus- (n = 46) based vaccines, as well as post-mRNA vaccination BTI caused by omicron (n = 28). Correlations between ADCC, binding, and NAb titers were reported. ADCC was elicited within the first month postinfection and -vaccination and remained detectable for ≥3 months. WT-infected symptomatic patients had higher S-specific ADCC levels than asymptomatic and vaccinated individuals. Also, no difference in N-specific ADCC activity was seen between symptomatic and asymptomatic patients, but the levels were higher than the inactivated vaccine. Notably, omicron infection showed reduced overall ADCC activity compared to WT SARS-CoV-2 infection. Although post-mRNA vaccination BTI elicited high levels of binding and NAbs, ADCC activity was significantly reduced. Also, there was no difference in ADCC levels across the four vaccines, although NAbs and binding antibody titers were significantly higher in mRNA-vaccinated individuals. All evaluated vaccine platforms are inferior in inducing ADCC compared to natural infection with WT SARS-CoV-2. The inactivated virus-based vaccine can induce N-specific ADCC activity, but its relevance to clinical outcomes requires further investigation. Our data suggest that ADCC could be used to estimate the extra-neutralization level against COVID-19 and provides evidence that vaccination should focus on other Fc-effector functions besides NAbs. Also, the decreased susceptibility of the omicron variant to ADCC offers valuable guidance for forthcoming efforts to identify the specific targets of antibodies facilitating ADCC.

A biological characterization of patients with postmenopausal Parkinson's disease.

Menopause increases the risk for Parkinson's disease (PD), although the underlying biological mechanisms have not been established in patients. Here, we aimed to understand the basis of menopause-related vulnerability to PD. Main motor and non-motor scores, blood levels of estradiol, testosterone, follicle-stimulating hormone, and luteinizing hormone, CSF levels of total α-synuclein, amyloid-ß-42, amyloid-ß-40, total tau, and phosphorylated-181-tau were examined in 45 women with postmenopausal-onset PD and 40 age-matched controls. PD patients had higher testosterone and lower estradiol levels than controls, and the residual estradiol production was associated with milder motor disturbances and lower dopaminergic requirements. In PD but not in controls, follicle-stimulating hormone levels correlated with worse cognitive scores and CSF markers of amyloidopathy and neuronal loss. In conclusion, menopause-related hormonal changes might differentially contribute to clinical-pathological trajectories of PD, accounting for the peculiar vulnerability to the disease.

Evaluation of Two-Assay Serological Testing Strategies for Anti-HCV Screening in Italian Populations: A Dual Screening Approach.

(1) Background: Hepatitis C virus (HCV) screening mostly uses a one-assay anti-HCV testing approach, which has a higher probability of false-positive results in populations with low HCV prevalence. (2) Methods: In this investigation, 17,926 participants were screened for HCV, and the reactives were tested using a two-assay anti-HCV approach: Elecsys ElectroChemiLuminescence (ECL) and a ChemiLuminescence ImmunoAssay (CLIA), respectively. A recombinant immunoblot assay (RIBA) was performed to confirm anti-HCV positivity. Statistical analysis was performed. (3) Results: A total of 350 specimens were reactive in the ECL screening, of which CLIA retesting showed that 292 (83.4%) were anti-HCV reactive (283 positives, 9 indeterminate, none negative by RIBA), but 58 (16.6%) were not anti-HCV reactive (15 positive, 12 indeterminate, 31 negatives by RIBA). The two-assay strategy significantly improved the positive predictive value (PPV: 95.00%) with χ2: 7.59 (p < 0.01) compared to the PPV assessed by one assay (PPV: 90.6%) with χ2: 34.51 (p < 0.001). The ROC curve defined a sensibility and specificity for the dual approach of 99.66% and 100.00%. (4) Conclusions: Compared with a one-assay testing strategy, the two-assay testing strategy may significantly reduce false positives in anti-HCV testing and identify inactive HCV infection in low seroprevalence populations.

OTX Genes in Adult Tissues.

OTX homeobox genes have been extensively studied for their role in development, especially in neuroectoderm formation. Recently, their expression has also been reported in adult physiological and pathological tissues, including retina, mammary and pituitary glands, sinonasal mucosa, in several types of cancer, and in response to inflammatory, ischemic, and hypoxic stimuli. Reactivation of OTX genes in adult tissues supports the notion of the evolutionary amplification of functions of genes by varying their temporal expression, with the selection of homeobox genes from the "toolbox" to drive or contribute to different processes at different stages of life. OTX involvement in pathologies points toward these genes as potential diagnostic and/or prognostic markers as well as possible therapeutic targets.

Validation of the New MINI-CUBE for Clinic Determination of Erythrocyte Sedimentation Rate.

Background: Erythrocyte sedimentation rate (ESR) indirectly measures blood fibrinogen, and it is altered by all those pathological conditions that modify the aggregation of red blood cells. The international guidelines by the International Council for Standardization in Hematology (ICSH) define the Westergren method as the gold standard for ESR, although it is completely operator-dependent, time-consuming, and requires a patient's blood consumption. Therefore, the validation of new ESR analyzers is needed. The aim of this study is the validation of a new automated ESR analyzer, MINI-CUBE (DIESSE, Diagnostica Senese, Italy). Methods: The samples (n = 270) were collected at the University Hospital of the University of Rome Tor Vergata. A comparison between the automated instrument and the gold standard was performed. Statistical analyses were processed by MedCalc software. Results: The comparison analysis performed on the overall samples reported a good agreement, showing a Spearman rank correlation coefficient of 0.94 (P < 0.001), compared to the Westergren test. The Bland-Altman analysis showed a mean bias of 1.5 (maximum (max.):19.6; minimum (min.): -16.6). Inter-run (level 1 coefficient of variation (CV): 4.9%; level 2 CV: 0.8%), intra-run (level 1 CV: 21.1%; level 2 CV: 3.2%), and inter-instrument (level 1 CV: 27.1%; level 2 CV: 5.6%) precision were also assessed. The hematocrit value did not interfere with the analysis: Spearman rank correlation coefficient of 0.929 (P < 0.001); mean bias of 1.3 (max.:18.3; min.: -15.6). Conclusions: Overall results from MINI-CUBE asserted a good correlation rate with the gold standard, and it could be considered an accurate, and objective alternative for the Westergren test.

The Role of Erythrocyte Sedimentation Rate (ESR) in Myeloproliferative and Lymphoproliferative Diseases: Comparison between DIESSE CUBE 30 TOUCH and Alifax Test 1.

(1) Background: The erythrocyte sedimentation rate (ESR) is widely diffused in hematology laboratories to monitor inflammatory statuses, response to therapies (such as antibiotics), and oncologic diseases. However, ESR is not a specific diagnostic marker but needs to be contextualized and compared with clinical and other laboratory findings. This study aimed to investigate the performance of two automated instruments, namely the DIESSE CUBE 30 TOUCH (DIESSE, Siena, Italy) and the Alifax Test 1 (Alifax Srl, Polverara, Italy), in comparison with the gold standard, the Westergren method, in lymphoproliferative and myeloproliferative patients. (2) Methods: 97 EDTA samples were selected from the hematology department of Roma Tor Vergata Hospital and analyzed. Statistical analysis was applied. (3) A good correlation between CUBE 30 TOUCH and the gold standard was observed in the overall sample (R2 = 0.90), as well as in patients with lymphoproliferative diseases (R2 = 0.90) and myeloproliferative diseases (R2 = 0.90). The correlation between Test 1 and the gold standard was observed in the overall sample (R2 = 0.68), as well as in patients with lymphoproliferative diseases (R2 = 0.79) and myeloproliferative diseases (R2 = 0.53). (4) Conclusions: The CUBE 30 TOUCH appears to be a more trustworthy tool for evaluating ESR in these pathologies.

The Antibodies' Response to SARS-CoV-2 Vaccination: 1-Year Follow Up.

The use of vaccines has allowed the containment of coronavirus disease 2019 (COVID-19) at a global level. The present work aims to add data on vaccination by evaluating the level of neutralizing antibodies in individuals who have received a three-vaccination series. For this purpose, we ran a surveillance program directed at measuring the level of IgG Abs against the Receptor Binding Domain (RBD) and surrogate virus neutralizing Ab (sVNT) anti-SARS-CoV-2 in the serum of individuals undergoing vaccination. This study was performed on employees from the University of Rome Tor Vergata and healthcare workers from the University Hospital who received the Vaxzevria vaccine (n = 56) and Comirnaty vaccine (n = 113), respectively. After the second dose, an increase in both RBD and sVNT Ab values was registered. In individuals who received the Comirnaty vaccine, the antibody titer was about one order of magnitude higher after 6 months from the first dose. All participants in this study received the Comirnaty vaccine as the third dose, which boosted the antibody response. Five months after the third dose, nearly one year from the first injection, the antibody level was >1000 BAU/mL (binding antibody units/mL). According to the values reported in the literature conferring protection against SARS-CoV-2 infection, our data indicate that individuals undergoing three vaccine doses present a low risk of infection.

Correlation between Chest Computed Tomography Score and Laboratory Biomarkers in the Risk Stratification of COVID-19 Patients Admitted to the Emergency Department.

BACKGROUND: It has been reported that mid-regional proadrenomedullin (MR-proADM) could be considered a useful tool to stratify the mortality risk in COVID-19 patients upon admission to the emergency department (ED). During the COVID-19 outbreak, computed tomography (CT) scans were widely used for their excellent sensitivity in diagnosing pneumonia associated with SARS-CoV-2 infection. However, the possible role of CT score in the risk stratification of COVID-19 patients upon admission to the ED is still unclear. AIM: The main objective of this study was to assess if the association of the CT findings alone or together with MR-proADM results could ameliorate the prediction of in-hospital mortality of COVID-19 patients at the triage. Moreover, the hypothesis that CT score and MR-proADM levels together could play a key role in predicting the correct clinical setting for these patients was also evaluated. METHODS: Epidemiological, demographic, clinical, laboratory, and outcome data were assessed and analyzed from 265 consecutive patients admitted to the triage of the ED with a SARS-CoV-2 infection. RESULTS AND CONCLUSIONS: The accuracy results by AUROC analysis and statistical analysis demonstrated that CT score is particularly effective, when utilized together with the MR-proADM level, in the risk stratification of COVID-19 patients admitted to the ED, thus helping the decision-making process of emergency physicians and optimizing the hospital resources.

Follow up and comparative assessment of IgG, IgA, and neutralizing antibody responses to SARS-CoV-2 between mRNA-vaccinated naïve and unvaccinated naturally infected individuals over 10 months.

BACKGROUND: Evidence on the effectiveness of vaccination-induced immunity compared to SARS-CoV-2 natural immunity is warranted to inform vaccination recommendations. AIM: In this study, we aimed to conduct a comparative assessment of antibody responses between vaccinated naïve (VN) and unvaccinated naturally infected individuals (NI) over 10 Months. METHOD: The study comprised fully-vaccinated naïve individuals (VN; n = 596) who had no history of SARS-CoV-2 infection, and received two doses of either BNT162b2 or mRNA-1273, and naturally infected individuals who had a documented history of SARS-CoV-2 infection and no vaccination record (NI cohort; n = 218). We measured the levels of neutralizing total antibodies (NtAbs), anti-S-RBD IgG, and anti-S1 IgA titers among VN and NI up to ∼10 months from administration of the first dose, and up to ∼7 months from SARS-CoV-2 infection, respectively. To explore the relationship between the antibody responses and time, Spearman's correlation coefficient was computed. Furthermore, correlations between the levels of NtAbs/anti-S-RBD IgG and NtAbs/anti-S1 IgA were examined through pairwise correlation analysis. RESULTS: Up to six months, VN individuals had a significantly higher NtAb and anti-S-RBD IgG antibody responses compared to NI individuals. At the 7th month, there was a significant decline in antibody responses among VN individuals, but not NI individuals, with a minimum decrease of 3.7-fold (p < 0.001). Among VN individuals, anti-S1 IgA levels began to decrease significantly (1.4-fold; p = 0.007) after two months, and both NtAb and S-RBD IgG levels began to decline significantly (NtAb: 2.0-fold; p = 0.042, S-RBD IgG: 2.4-fold; p = 0.035) after three months. After 10 months, the most significant decline among VN individuals was observed for S-RBD-IgG (30.0-fold; P < 0.001), followed by NtAb (15.7-fold; P < 0.001) and S-IgA (3.7-fold; P < 0.001) (most stable). Moreover, after 5 months, there was no significant difference in the IgA response between the two groups. CONCLUSION: These findings have important implications for policymakers in the development of vaccination strategies, particularly in the consideration of booster doses to sustain long-lasting protection against COVID-19.

Partial Loss of Function ABCA12 Mutations Generate Reduced Deposition of Glucosyl-Ceramide, Leading to Patchy Ichthyosis and Erythrodermia Resembling Erythrokeratodermia Variabilis et Progressiva (EKVP).

Ichthyoses are genetically determined cornification disorders of the epidermis characterized by the presence of different degrees of scaling, hyperkeratosis, and erythroderma often associated with palmoplantar keratoderma. Different classifications of these diseases have been proposed, often based upon the involved genes and/or the clinical presentation. The clinical features of these diseases present some overlap of phenotypes among distinct genetic entities, depending mainly on the penetrance of mutations. In this study, using a clinical, genetic, and molecular approach, we analyzed a family with two affected members who had clinical and histological features resembling erythrokeratodermia variabilis (EKV) or a type of erythrodermic hyperkeratosis with palmoplantar keratoderma. Despite of the clinical presentation, we demonstrated that the affected patients were genetically double heterozygous for two different mutations in the ABCA12 gene, known to be responsible for harlequin ichthyosis. To explain the mild phenotype of our patients, we performed a molecular characterization of the skin. In the upper layers of the epidermis, the results showed a patchy presence of the glucosyl-ceramides (GlcCer), which is the lipid transported by ABCA12, fundamental in contributing to skin impermeability. Indeed, the two mutations detected do not completely abolish ABCA12 activity, indicating that the mild phenotype is due to a partial loss of function of the enzyme, thus giving rise to an intermediate phenotype resembling EKVP, due to a partial depletion of GlcCer deposition.

Saliva as Biomarker for Oral and Chronic Degenerative Non-Communicable Diseases.

Saliva is a very complex fluid and it is essential to maintain several physiological processes and functions, including oral health, taste, digestion and immunological defenses. Saliva composition and the oral microbiome can be influenced by several factors, like diet and smoking habits, and their alteration can represent an important access point for pathogens and, thus, for systemic illness onset. In this review, we explore the potentiality of saliva as a new tool for the early detection of some pathological conditions, such as oral diseases, chronic degenerative non-communicable diseases, among these chronic kidney disease (CKD). We also examined the possible correlation between oral and systemic diseases and oral and gut microbiota dysbiosis. In particular, we deeply analyzed the relationship between oral diseases and CKD. In this context, some salivary parameters can represent a new device to detect either oral or systemic pathologies. Moreover, the positive modulation of oral and gut microbiota induced by prebiotics, postbiotics, or symbiotics could represent a new possible adjuvant therapy in the clinical management of oral diseases and CKD.

Urine Parameters in Patients with COVID-19 Infection.

A urine test permits the measure of several urinary markers. This is a non-invasive method for early monitoring of potential kidney damage. In COVID-19 patients, alterations of urinary markers were observed. This review aims to evaluate the utility of urinalysis in predicting the severity of COVID-19. A total of 68 articles obtained from PubMed studies reported that (i) the severity of disease was related to haematuria and proteinuria and that (ii) typical alterations of the urinary sediment were noticed in COVID-19-associated AKI patients. This review emphasizes that urinalysis and microscopic examination support clinicians in diagnosing and predicting COVID-19 severity.