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Claudio Sopranzetti, Sara Fabbri, Chiara Natalucci, Il re di Bangkok, Torino, Add Editore, 2019, pp. 218
Full text linkBook review of Claudio Sopranzetti, Sara Fabbri, Chiara Natalucci, Il re di Bangkok, Torino, Add Editore, 2019, pp. 218.Recensione di Claudio Sopranzetti, Sara Fabbri, Chiara Natalucci, Il re di Bangkok, Torino, Add Editore, 2019, pp. 218
An interview with Dr Chiara Fabbri: pharmacogenomics and drug repurposing for treatment-resistant depression
No full textClinical effects of adjunctive therapeutic devices in non-surgical treatment of periodontitis patients
No full textBACKGROUND. Periodontitis is an infectious-inflammatory disease affecting the tooth-supporting tissues. If untreated, periodontitis may lead to progressive loss of periodontal attachment and spontaneous tooth exfoliation. Non-surgical instrumentation of the tooth surfaces, consisting of the professional removal of sub-gingival biofilm and calculus, is the cornerstone of cause-related periodontitis therapy. Despite the improvement in terms of clinical parameters, the mechanical therapy alone may fail to fully eliminate pathogenic bacterial, especially from reservois in the soft tissue, root cement, dentinal tubules and from areas that are inaccessible to periodontal instruments, such as deep pockets, furcation areas and root depressions.
AIM. This Ph.D. program aimed at evaluating the adjunctive effect of different procedures over standard scaling and root planing (SRP) in the treatment of moderate to severe periodontitis (stage III and IV).
I) Phototerapic protocol in treatment of periodontitis
Materials and methods. We established an examiner-blind, randomized, controlled, split-mouth, multi-center trial with a total of 60 participants. Pocket depth (PD), recession (REC), clinical attachment level (CAL), bleeding on probing (BOP) and plaque score were recorded. Two sextants were selected and randomized, receiving standard SRP either alone (control sextant) or with adjunctive PTP (test sextant). Participants were recalled at 6, 12 and 24 weeks after treatment for parameters re-evaluation.
Results. No statistically significant differences were observerd in mean (± standard deviation) CAL change from baseline to week 24 (p=0.212) and for the other parameters (CAL change at all sites, PD change at either deep sites or all sites, BOP, plaque scores) for all change intervals assessed (p>0.05). Evaluating the pocket closure outcome (PD≤ 4 mm and BOP negative), there was no difference observed between test and control sextants.
ii) Sub-gingival air-polishing with erythritol in the treatment of periodontitis
Materials and methods. A bi-center, parallel-arm, randomized, controlled, single-blind clinical trial was
established with a total of 40 subjects. Baseline values of PD, REC, CAL, BOP and plaque score were recorded. Subjects were treated according to randomization, receiving full-mouth standard ultrasonic SRP alone (control group) or full-mouth ultrasonic SRP in association with sub-gingival treatment with erythritol powder (test group) in the experimental sites. Periodontal parameters were re-assessed at 12 weeks following treatment administration.
Results. From baseline to 12 weeks, mean CAL, PD values and BOP score significantly (p<0.005) decreased in control and test group, without significant difference between groups. Interestingly, 44.7% (control) and 47.9% (test) of experimental sites shifted to PD<4mm and BOP negative condition, with no significant inter-group difference (p = 0.64). The average overall pocket closure, considering sites with PD<4mm, both BOP positive and negative, was 77.6% for control group and 80% for test group.
CONCLUSIONS. The adjunctive treatments evaluated failed to provide any additional clinical benefits to standard periodontal non-surgical therapy alone, resulting in similar clinical parameter improvement without statistical significant difference between control and test group. SRP is still considered the primary therapeutic modality for non‐surgical periodontal therapy and further research is required to identify adjuncts that can enhance its beneficial effects in the treatment of the disease.INTRODUZIONE. La parodontite è una malattia infettiva-infiammatoria che colpisce i tessuti di supporto degli elementi dentari. Se non trattata, essa può portare alla perdita progressiva dell'attacco parodontale, fino a culminare con l’esfoliazione spontanea dei denti. La strumentazione non-chirurgica, che consiste nella rimozione professionale del tartaro e del biofilm sub-gengivale (SRP), è la pietra miliare della terapia causale della parodontite. Nonostante il significativo miglioramento dei parametri clinici, la sola SRP potrebbe non riuscire ad eliminare completamente i batteri patogeni, trattenuti soprattutto in reservois tissutali (tessuti molli, cemento radicolare, tubuli dentinali) ed in aree poco accessibili agli strumenti convenzionali (tasche profonde, forcazioni, depressioni radicolari).
OBIETTIVO. Valutare l'effetto clinico di diverse procedure aggiuntive ad SRP nel trattamento non chirurgico della parodontite di grado moderato e grave (stadio III e IV).
I) Protocollo foto-terapico (PTP) nel trattamento della parodontite
Materiali e metodi. È stato istituito uno studio multi-centrico, singolo cieco, randomizzato, controllato, split-mouth con un totale di 60 pazienti.
Sono stati registrati profondità di tasca (PD), recessione (REC), livello di attacco clinico (CAL), sanguinamento al sondaggio (BOP) ed indice di placca. Sono randomizzati due sestanti che hanno ricevuto la sola SRP (controllo) o SRP con PTP aggiuntivo (test). I partecipanti sono stati rivalutati a 6, 12 e 24 settimane dopo il trattamento.
Risultati. Non si sono osservate differenze statisticamente significative nella variazione media (± deviazione standard) di CAL dal baseline alla settimana 24 post-trattamento nei siti con PD ≥ 5 mm al baseline (p = 0.212), né per altri parametri (variazione di CAL in tutti i siti, modifica di PD nei siti profondi o in tutti i siti, BOP, indice di placca placca) a tutti gli intervalli temporali (p> 0.05). Valutando l'esito della chiusura della tasche (PD≤ 4 mm e BOP negativo), non è stata osservata alcuna differenza.
ii) air-polishing sub-gengivale con polvere di eritritolo nel trattamento della parodontite
Materiali e metodi. È stato progettato e stabilito uno studio clinico bi-centrico, in singolo cieco, randomizzato, controllato, a bracci paralleli con un totale di 40 soggetti.
Sono stati registrati PD, REC, CAL, BOP ed indice di placca per ciascun partecipante. I soggetti sono stati trattati in base alla randomizzazione, ricevendo solo SRP con device ad ultrasuoni (controllo) o SRP ad ultrasuoni in associazione con il trattamento sub-gengivale con polvere di eritritolo (test). I parametri parodontali sono stati rivalutati a 12 settimane dopo il trattamento.
Risultati. Dal baseline a 12 settimane, la variazione media di CAL, i valori di PD e di BOP sono diminuiti in modo significativo (p <0.005) nel gruppo di controllo e nel gruppo di test, senza differenze significative. Da notare che il 44.7% (controllo) ed il 47.9% (test) dei siti sperimentali sono passati a PD <4 mm e condizione negativa di BOP, senza però differenze significative tra i gruppi (p = 0.64). La chiusura complessiva media delle tasche, considerando i siti con PD <4 mm, sia BOP positivi che negativi, è stata del 77.6% per il gruppo controllo e dell'80% per il gruppo test.
CONCLUSIONI. I trattamenti aggiuntivi valutati non sono riusciti a fornire un significativo beneficio addizionale alla terapia parodontale non-chirurgica (SRP), con conseguente simile miglioramento dei parametri clinici. SRP è ancora considerata la modalità terapeutica primaria per la terapia parodontale non-chirurgica e sono necessarie ulteriori ricerche per identificare le procedure aggiuntive che possano aumentare i suoi effetti clinici nel trattamento della malattia
Genetics of long-term treatment outcome in bipolar disorder
No full textBipolar disorder (BD) shows one of the strongest genetic predispositions among psychiatric disorders and the identification of reliable genetic predictors of treatment response could significantly improve the prognosis of the disease.The present study investigated genetic predictors of long-term treatment-outcome in 723 patients with BD type I from the STEP-BD (Systematic Treatment Enhancement Program for Bipolar Disorder) genome-wide dataset. BD I patients with >. 6. months of follow-up and without any treatment restriction (reflecting a natural setting scenario) were included. Phenotypes were the total and depressive episode rates and the occurrence of one or more (hypo)manic/mixed episodes during follow-up. Quality control of genome-wide data was performed according to standard criteria and linear/logistic regression models were used as appropriate under an additive hypothesis. Top genes were further analyzed through a pathway analysis.Genes previously involved in the susceptibility to BD (DFNB31, SORCS2, NRXN1, CNTNAP2, GRIN2A, GRM4, GRIN2B), antidepressant action (. DEPTOR, CHRNA7, NRXN1), and mood stabilizer or antipsychotic action (NTRK2, CHRNA7, NRXN1) may affect long-term treatment outcome of BD. Promising findings without previous strong evidence were TRAF3IP2-AS1, NFYC, RNLS, KCNJ2, RASGRF1, NTF3 genes. Pathway analysis supported particularly the involvement of molecules mediating the positive regulation of MAPK cascade and learning/memory processes.Further studies focused on the outlined genes may be helpful to provide validated markers of BD treatment outcome
Pharmacogenetics of Major Depressive Disorder: Top Genes and Pathways Toward Clinical Applications
No full textThe pharmacogenetics of antidepressants has been not only a challenging but also frustrating research field since its birth in the 1990s. Indeed, great expectations followed the first evidence of familiar aggregation of antidepressant response. Despite the progress from candidate gene studies to genome-wide association studies (GWAS), results fell out the expectations and they were often inconsistent. Anyway, the cumulative evidence supports the involvement of some genes and molecular pathways in antidepressant efficacy. The best single genes are SLC6A4, HTR2A, BDNF, GNB3, FKBP5, ABCB1, and cytochrome P450 genes (CYP2D6 and CYP2C19). Molecular pathways involved in inflammation and neuroplasticity show the greatest support. The first studies evaluating benefits of genotype-guided antidepressant treatments provided encouraging results and confirmed the relevance of SLC6A4, HTR2A, ABCB1, and cytochrome P450 genes. Further progress in genotyping and data analysis would allow to move forward and complete the understanding of antidepressant pharmacogenetics and its translation into clinical applications
Predictors of switch from depression to mania in bipolar disorder
No full textManic switch is a relevant issue when treating bipolar depression. Some risk factors have been suggested, but unequivocal findings are lacking. We therefore investigated predictors of switch from depression to mania in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) sample. Manic switch was defined as a depressive episode followed by a (hypo)manic or mixed episode within the following 12 weeks. We assessed possible predictors of switch using generalized linear mixed models (GLMM).8403 episodes without switch and 512 episodes with switch (1720 subjects) were included in the analysis. Several baseline variables were associated with a higher risk of switch. They were younger age, previous history of: rapid cycling, severe manic symptoms, suicide attempts, amphetamine use and some pharmacological and psychotherapeutic treatments. During the current depressive episode, the identified risk factors were: any possible mood elevation, multiple mania-associated symptoms with at least moderate severity, and comorbid panic attacks.In conclusion, our study suggests that both characteristics of the disease history and clinical features of the current depressive episode may be risk factors for manic switch
22q11.2 rearrangements: clinical and research implications of population-based risk of neuropsychiatric and developmental disorders
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Role of 108 schizophrenia-associated loci in modulating psychopathological dimensions in schizophrenia and bipolar disorder
No full textThe Schizophrenia Working Group of the Psychiatric Genomics Consortium (PGC) identified 108 loci associated with schizophrenia, but their role in modulating specific psychopathological dimensions of the disease is unknown. This study investigated which symptom dimensions may be affected by these loci in schizophrenia, and bipolar disorder. Positive, negative and depressive symptoms, suicidal ideation, cognition, violent behaviors, quality of life, and early onset were investigated in schizophrenia and bipolar disorder using the clinical antipsychotic trials of intervention effectiveness (CATIE) and systematic treatment enhancement program for bipolar disorder (STEP-BD) studies. Individual loci were investigated, then genes within 50 Kbp from polymorphisms with p < 0.10 were included in an enrichment analysis (Cytoscape GeneMania plugin) and used to estimate polygenic risk scores (PRS). Covariates were center, age, gender, ancestry-informative population, principal components, and for cognition, also years of education were considered. Eighty-nine polymorphisms were available, 479 and 810 white subjects were included from CATIE and STEP-BD, respectively. rs75059851 (IGSF9B gene) was associated with negative symptoms in CATIE (p = 0.00048). Genes within 50 Kbp from variants contributing to negative symptoms and suicide were enriched with GO terms involved in acetylcholine neurotransmission, cognition showed enrichment with GO terms involved in vitamin B6 and fucose metabolism while early onset with GO terms related to extracellular matrix structure. PRS showed nominal associations with violent behaviors and depressive symptoms. This study provided preliminary evidence that a schizophrenia-associated variant (rs75059851) may modulate negative symptoms. Multi-locus models may provide interesting insights about the biological mechanisms that mediate psychopathological dimensions
A model to investigate SNPs' interaction in GWAS studies
No full textGenome-wide association studies (GWAS) are able to identify the role of individual SNPs in influencing a phenotype. Nevertheless, such analysis is unable to explain the biological complexity of several diseases. We elaborated an algorithm that starting from genes in molecular pathways implicated in a phenotype is able to identify SNP-SNP interaction's role in association with the phenotype. The algorithm is based on three steps. Firstly, it identifies the biological pathways (gene ontology) in which the genes under analysis play a role (GeneMANIA). Secondly, it identifies the group of SNPs that best fits the phenotype (and covariates) under analysis, not considering individual SNP regression coefficients but fitting the regression for the group itself. Finally, it operates an analysis of SNP interactions for each possible couple of SNPs within the group. The sensitivity and specificity of our algorithm was validated in simulated datasets (HapGen and Simulate Phenotypes programs). The impact on efficiency deriving from changes in the number of SNPs/patients under analysis, linkage disequilibrium and minor allele frequency thresholds was analyzed. Our algorithm showed a strong stability throughout all analysis operated, resulting in an overall sensitivity of 81.67 % and a specificity of 98.35 %. We elaborated a stable algorithm that may detect SNPs interactions, especially those effects that pass undetected in classical GWAS. This method may contribute to face the two relevant limitations of GWAS: lack of biological informative power and amount of time needed for the analysis
COVID-19 hospitalization rates in individuals with substance or alcohol use disorders
No full textPeople with Substance or Alcohol Use Disorders (SUDs/AUDs) are likely to be more vulnerable to COVID-19 infection than the general population.We performed a cross-sectional study to compare the hospitalization rate (CHR) for COVID-19 in 2020 in patients diagnosed with SUDs or AUDs in the previous 10 years vs the population without these disorders (NAS).We included individuals who were resident in the Metropolitan Area of Bologna (Northern Italy). People with SUDs or AUDs have a greater probability of being hospitalized for COVID-19 infection compared to the general population NAS, suggesting that they suffer from worse physical symptoms/conditions than the general population.Furthermore, we found higher mortality rates during hospitalization for COVID-19 in patients with AUDs or SUDs than the general population NAS.These findings highlight the importance of a careful monitoring and early intervention measures in these patients
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