Deregulated cellular circuits driving immunoglobulins and complement consumption associate with the severity of COVID-19 patients

SARS-CoV-2 infection causes an abrupt response by the host immune system, which is largely responsible for the outcome of COVID-19. We investigated whether the specific immune responses in the peripheral blood of 276 patients were associated with the severity and progression of COVID-19. At admission, dramatic lymphopenia of T, B, and NK cells is associated with severity. Conversely, the proportion of B cells, plasmablasts, circulating follicular helper T cells (cTfh) and CD56^–CD16⁺ NK-cells increased. Regarding humoral immunity, levels of IgM, IgA, and IgG were unaffected, but when degrees of severity were considered, IgG was lower in severe patients. Compared to healthy donors, complement C3 and C4 protein levels were higher in mild and moderate, but not in severe patients, while the activation peptide of C5 (C5a) increased from the admission in every patient, regardless of their severity. Moreover, total IgG, the IgG1 and IgG3 isotypes, and C4 decreased from day 0 to day 10 in patients who were hospitalized for more than two weeks, but not in patients who were discharged earlier. Our study provides important clues to understand the immune response observed in COVID-19 patients, associating severity with an imbalanced humoral response, and identifying new targets for therapeutic intervention.     

Assessment of Hounsfield unit in the differential diagnosis of odontogenic cysts

Objectives:The purpose of this study was to evaluate the usefulness of Hounsfield unit (HU) assessment with multislice-CT in the differentiation of radicular cysts (RCs), dentigerous cysts (DCs) and odontogenic keratocysts (OKCs).Methods:In total, 307 odontogenic cysts (RCs, DCs and OKCs) were included in this study. Cysts with lesion diameter <10 mm, cysts with artefacts affecting measurement of HU values, cysts involving infection and recurrent cysts were regarded as exclusion criteria. Images were acquired in three different types of CT scanners: Aquilion ONE, Discovery CT750 HD and SOMATOM Definition Flash. Differences in HU values among scanners and among types of odontogenic cysts were assessed using one-way analysis of variance; multiple comparisons were performed post hoc, using the Tukey–Kramer honestly significant difference test.Results:In total, 164 cysts were analysed in this study (64 RCs, 57 DCs and 43 OKCs). Regardless of the type of lesion, the Aquilion ONE scanner demonstrated a significant difference in HU value, compared with the Discovery CT750 HD scanner. Regardless of CT scanner model, HU values significantly differed between DCs and OKCs (p < 0.0001), as well as between OKCs and RCs (p < 0.0001).Conclusions:HU values were found to vary among CT scanners and should always be associated with other lesion imaging features while interpreting and elaboration diagnostic hypothesis. Notably, the results suggested that OKCs might be able to be differentiated from DCs and RCs by using HU values.     

Detection of cytokeratins in ghost cells of calcifying cystic odontogenic tumor indicates an altered keratinization and hair follicle differentiation for their development

Calcifying cystic odontogenic tumors (CCOTs) are benign cystic lesions of odontogenic origin characterized by an ameloblastoma-like epithelium and the presence of a group of cells named ghost cells. The pattern of cytokeratin (Ck) expression on these lesions remains unclear and needs to be clarified. To this end, the expression of Ck6, Ck13, Ck14, Ck18, and Ck19 in the epithelium lining of 7 cases of CCOTs was evaluated by immunohistochemistry. For this, the epithelium lining was divided into 3 distinct regions: basal layer, suprabasal layer, and the compartment composed of ghost cells. In this study, 6 cases (85.7%) were classified as type 1 and 1 (14.3%) as type 4. All cases were negative for Ck13 and Ck18, despite the epithelial layer, as well as in the ghost cells. Ck6 was only positive in the ghost cells. Positivity for Ck14 and Ck19 was found in the basal and suprabasal layers, including the ghost cells. The results showing positivity for Ck14 and Ck19 in all of the analyzed cases reinforce CCOT as being of odontogenic origin, and the restricted expression of Ck6 in the ghost cells may be indicative that these cells suffer an altered differentiation into hair follicles in CCOTs.     

Novel optimized biopolymer-based nanoparticles for nose-to-brain delivery in the treatment of depressive diseases

A valid option to bypass the obstacle represented by the blood–brain barrier (BBB) in brain delivery is the use of the unconventional intranasal route of administration. The treatment of depressive diseases, resulting from the depletion of a neurotransmitter in the inter-synaptic space, such as serotonin, is indirectly treated using molecules that can permeate the BBB unlike the latter. In the present article, a set of nanovectors were produced using a mucoadhesive biopolymer, i.e. alginate (Alg). Optimizing the reaction, polymeric nanoparticles having diameter of 30–70 nm were produced, and water stable multi-walled carbon nanotubes functionalized (MWCNT-COOH)/Alg complexes were obtained. These nanovectors were loaded with serotonin, evaluating drug loading/release. By means of Raman microscopy, the cellular internalization of the (MWCNT-COOH)/Alg complex was demonstrated. A complete biocompatibility on neuronal cells was proved for the whole set of nanovectors. Finally, a method of self-administration was tested, which involves the use of a household apparatus, such as an aerosol machine, observing a fine particulate, able to deliver the nanovectors through the nose.

A valid option to bypass the obstacle represented by the blood–brain barrier (BBB) in brain delivery is the use of the unconventional intranasal route of administration.     

Genes in the pathway of tooth mineral tissues and dental caries risk: a systematic review and meta-analysis

Objectives

To perform a systematic review of the literature, investigating the influence of tooth mineral tissues genes on dental caries.

Materials and methods

Five databases were searched. Only human studies with cross-sectional, longitudinal, and case-control design were included. Meta-analysis was performed for each polymorphism, providing allele and genotype estimates. A meta-analysis was performed, pooling several polymorphisms for each gene. A Funnel Plot and Egger’s test were also performed.

Results

A total of 1124 records were found. Of these, 25 papers were included in the systematic review and 18 in the meta-analysis. Most of the studies (52%) were of medium quality. With regard to the allele analysis, the T allele of rs134136 (TFIP11) (OR 1.51; 95%CI 1.02–2.22) showed an association with high experience of caries and the summarization of polymorphisms investigated in the TFIP11 gene, after exclusion of SNP linkage disequilibrium, showed an association with caries experience (OR 1.64; 95%CI 1.08–2.50). An analysis of the homozygous genotype did not show any significant association. The pooled SNPs of AMBN showed associations with caries (OR 0.45; 95%CI 0.29–0.72). The pooled polymorphisms of AMELX were associated with caries experience (OR 1.78; 95%CI 1.23–2.56). In the analysis of the homozygous genotype, no SNP showed a significant association. Egger’s test showed no significant publication bias for all models (p > 0.05).

Conclusion

The present findings showed that the genes TFIP11, AMBN, and AMELX play an important role in dental caries.

Clinical relevance

Several single nucleotide polymorphisms related to the genes in the formation of tooth mineral are linked to the occurrence of dental caries, and these genes have proved to be important for an explanation of differences in the risk of dental caries.

     

Risk factors for transient dysfunction of gas exchange after cardiac surgery

Objective

A retrospective cohort study was preformed aiming to verify the presence of transient dysfunction of gas exchange in the postoperative period of cardiac surgery and determine if this disorder is linked to cardiorespiratory events.

Methods

We included 942 consecutive patients undergoing cardiac surgery and cardiac procedures who were referred to the Intensive Care Unit between June 2007 and November 2011.

Results

Fifteen patients had acute respiratory distress syndrome (2%), 199 (27.75%) had mild transient dysfunction of gas exchange, 402 (56.1%) had moderate transient dysfunction of gas exchange, and 39 (5.4%) had severe transient dysfunction of gas exchange. Hypertension and cardiogenic shock were associated with the emergence of moderate transient dysfunction of gas exchange postoperatively (P=0.02 and P=0.019, respectively) and were risk factors for this dysfunction (P=0.0023 and P=0.0017, respectively). Diabetes mellitus was also a risk factor for transient dysfunction of gas exchange (P=0.03). Pneumonia was present in 8.9% of cases and correlated with the presence of moderate transient dysfunction of gas exchange (P=0.001). Severe transient dysfunction of gas exchange was associated with patients who had renal replacement therapy (P=0.0005), hemotherapy (P=0.0001), enteral nutrition (P=0.0012), or cardiac arrhythmia (P=0.0451).

Conclusion

Preoperative hypertension and cardiogenic shock were associated with the occurrence of postoperative transient dysfunction of gas exchange. The preoperative risk factors included hypertension, cardiogenic shock, and diabetes. Postoperatively, pneumonia, ventilator-associated pneumonia, renal replacement therapy, hemotherapy, and cardiac arrhythmia were associated with the appearance of some degree of transient dysfunction of gas exchange, which was a risk factor for reintubation, pneumonia, ventilator-associated pneumonia, and renal replacement therapy in the postoperative period of cardiac surgery and cardiac procedures.