Insight into susceptibility genes associated with bipolar disorder: a systematic review.

OBJECTIVE: Bipolar disorder (BD) is a severe disorder, and it is associated with an increased risk of mortality. About 25% of patients with BD have attempted and 11% have died by suicide. All these characteristics suggest that the disorders within the bipolar spectrum are a crucial public health problem. With the development of molecular genetics in recent decades, it was possible to more easily detect risk genes associated with this disorder. This study aimed at summarizing the findings of systematic reviews and meta-analyses on the topic and assessing the quality of the available evidence. MATERIALS AND METHODS: PubMed/Medline and Web of Science were searched to identify systematic reviews and meta-analyses published during 2013-2019. Standard methodology was applied to synthesize and assess the retrieved literature. RESULTS: This systematic review identifies a number of potential risk genes associated with bipolar disorder whose mechanism of action has yet to be confirmed. They are divided into several groups: 1) a list of the most significant susceptibility genetic factors associated with BD; 2) the implication of the ZNF804A gene in BD; 3) the role of genes involved in calcium signaling in BD; 4) DNA methylation in BD; 5) BD and risk suicide genes; 6) susceptibility genes for early-onset BD; 7) candidate genes common to both BD and schizophrenia; 8) genes involved in cognitive status in BD cases; 9) genes involved in structural alteration in BD brain tissue; 10) genes involved in lithium response in BD. CONCLUSIONS: Future research should concentrate on molecular mechanisms by which genetic variants play a major role in BD. Supplemental research is needed to replicate the applicable results.

Effect of surgery, delivery device and head position on sinus irrigant penetration in a cadaver model.

OBJECTIVE: The extent of surgery, the type of device used and head position may influence nasal irrigation. The aim of this study was to determine the effectiveness of topical irrigant delivery to the paranasal sinuses according to these factors. METHOD: Four cadaveric heads underwent four stepwise endoscopic dissections. Irrigations were evaluated after every stage using different delivery devices (squeeze-bottle, gravity-dependent device and syringe) in two head positions (nose-to-sink and vertex down). Irrigant penetration into each sinus was estimated using a four-point scale. RESULTS: A significant positive effect of surgery was demonstrated for each sinus as well as for the delivery device. High-volume irrigant devices are more effective, and the head position plays a significant role in irrigant distribution to the frontal sinus. CONCLUSION: This study further confirms the efficacy of high-volume irrigant devices. A vertex down position during the irrigation could improve delivery to the frontal sinus, and the widening of the ostia increases irrigant access to the sinuses.

Double-blind, randomised controlled trial on the efficacy of saline nasal irrigation with sodium hyaluronate after endoscopic sinus surgery.

OBJECTIVE: There is a growing interest in sodium hyaluronate for the clinical management of patients who undergo functional endoscopic sinus surgery for chronic rhinosinusitis, because of the mucosal regenerative properties of this macromolecule. However, its role in post-operative care is still debated. This study aimed to evaluate the effect of sodium hyaluronate administered via nasal irrigation with saline, in the post-operative period, after functional endoscopic sinus surgery. METHODS: A multicentric, prospective, randomised, double-blind, parallel group study was conducted on 56 consecutive patients who underwent functional endoscopic sinus surgery for chronic rhinosinusitis without polyps. Group 1 received the standard therapy of normal saline; group 2 received saline plus sodium hyaluronate. RESULTS: Both objective and subjective measurements, in terms of endoscopic appearance and patient-reported satisfaction, were significantly better in group 2 compared to group 1. CONCLUSION: Sodium hyaluronate may be a useful adjunct to nasal saline irrigation in the early post-operative period following functional endoscopic sinus surgery.

Frontal sinus ablation (Riedel-Mosher’s procedure): indications and role in the endonasal endoscopic era.

BACKGROUND: The aim of this article is to describe the Riedel-Mosher’s surgical technique and identify its current role in the endoscopic endonasal era based on the experience of a tertiary care medical centre. It also provides a brief excursus on materials available for frontal reconstruction. METHODS: A retrospective review of patients submitted to Riedel-Mosher’s procedure from 2005 to 2018 at a single tertiary care centre was carried out. Details of the surgical technique along with data on frontal reconstruction timing and materials used were collected. RESULTS: A total of 21 patients (16 males and 5 females) underwent the Riedel-Mosher’s procedure. The age of the patients ranged from 15 to 84 years. The underlying pathology was represented mainly by chronic osteitis of the frontal bone (17 cases), followed by benign tumours (3 cases) and malignancy (1 case). Perioperative complications occurred in 3 patients. Cranioplasty was carried out only on 16 cases and delayed by an average time of 10 months. Materials for reconstruction included titanium, ceramic, plastic and free flap . CONCLUSIONS: Nowadays, Riedel-Mosher’s procedure is still indicated in selected cases of benign and malignant pathologies of the frontal sinus and/or frontal bone. Surgical expertise is key to approach the frontal sinus safely. Its reconstruction requires proper planning and a wide variety of materials to perform it is now available.

Stigma, grief and depressive symptoms in help-seeking people bereaved through suicide.

BACKGROUND: The painful experience of mourning after suicide can be further complicated by the stigma surrounding suicide survival. We investigated how grief and depression influence the perception of stigma towards survivors in a sample of help-seeking persons bereaved through suicide. METHODS: Cross-sectional design. Information on sociodemographic variables and responses to the Stigma of Suicide Survivor Scale, Beck Depression Inventory (BDI) and Inventory of Complicated Grief (ICG) was collected from 240 people bereaved through suicide who consecutively accessed an online support initiative. RESULTS: Despite the strong correlation between ICG and BDI scores, the intensity of depressive but not of grief symptoms was related to perceived stigma towards survivors. Time since loss was also positively related to levels of perceived stigma against survivors. The links between depression and perceived stigma persisted after taking into account relationship with the deceased and other sociodemographic factors. LIMITATIONS: The main study limitations are the cross-sectional design, reliance on self-report measures, and the self-selection of the sample of people bereaved through suicide, seeking help through a website. Social support was not measured and the sample included a large proportion of women. CONCLUSIONS: Specific interventions designed for persons bereaved by suicide should consider that psychological distress and mourning are qualitatively different reactions to a suicide loss. The relationship among perceived stigma, depressive suffering and time elapsed since the suicide loss suggests the usefulness of closely investigating the experience of stigma in all people bereaved through suicide with depressive symptoms, even long after the event.

Targeting patients' microbiota with probiotics and natural fibers in adults and children with constipation.

OBJECTIVE: Functional constipation (FC) is a common condition in which the gut microbiota composition plays a fundamental role. The increasing knowledge on the role of gut microbes in the regulation of gut motility and stool consistency has allowed reconsidering, with a new scientific-based approach, the possibility to target the composition of intestinal bacterial populations for FC treatment. In this review, we evaluate recent attempts that used prebiotics, natural fibers or probiotics to treat FC, with a deep microbiome-based focus. MATERIALS AND METHODS: This is a literature review of articles published in Medline, Web of Science, and the Cochrane Library. Studies on FC in adults and children were identified using the following terms: constipation AND probiotics OR prebiotics OR synbiotics PR fibers OR microbiome OR microbiota. Selected animal studies were also considered if showing mechanistic observations. RESULTS: FC is associated with alteration in microbiome composition. Motility and fecal consistency are affected with different efficacy by the type of fiber, prebiotic or probiotic strain used in patients. CONCLUSIONS: Selected bacterial strains, mainly belonging to the Bifidobacterium genus, and some poorly or non-fermented natural fibers, such as Psyllium, may significantly improve FC and may represent the basis for an effective supplementation.

Probiotics, prebiotics and synbiotics for weight loss and metabolic syndrome in the microbiome era.

OBJECTIVE: Excessive body fat and the associated dysmetabolic consequences affect both developed and emerging countries. An altered gut microbiota composition is an important environmental cause of these conditions. Clinical trials targeting gut microbiome composition or functions with pro or prebiotics to promote a healthier profile are considered a promising tool for excessive body weight treatment and prevention of dysmetabolic complications. MATERIALS AND METHODS: We searched PubMed and Cochrane Library using combinations of probiotics/prebiotics and synbiotics with obesity/weight loss/metabolic syndrome as the search terms. Clinical studies and significant pre-clinical results showing molecular mechanisms supporting clinical results were also discussed. RESULTS: Several studies in humans and in animal models have elucidated biological mechanisms supporting the observed clinical efficacy of selected probiotic and prebiotic compounds for weight management. Efficacy appears to be species or strain-specific. Fibers such as inulin or galactomannan promote independent and synergistic beneficial effects. CONCLUSIONS: Diet supplementation with synbiotics prepared using selected strains (such as Lactobacillus gasseri strains) showed to exert weight-reduction and anti-inflammatory activity in large independent studies. Their administration, together with galactomannan and/or inulin fibers, may increase weight management effects due to synergistic effect on short chain fatty acid production and microbiota 're-configuration'.

Implementing strategies for data collection in chronic rhinosinusitis.

SUMMARY: Chronic rhinosinusitis (CRS) is a debated topic in the international rhinologic literature because of its high prevalence, heterogeneity of clinical manifestations and unpredictability of disease course. Recently, the focus in CRS research has moved to identify biological subtypes that might explain its aetiology and clinical variability. However, these analyses are still expensive and limited to scientific purposes, so that they cannot be used on a large scale in daily practice. For this reason, we wondered if it was possible to define a risk stratification for CRS patients based only on first level investigations. The heterogeneity of the disease has given us a large amount of data compelling to find an additional storage system. Herein, we present the results of our work, the RhinoBank, as we believe that it is an easy-to-use tool for those professionals dealing with CRS and an effective system to exploit in clinical research.

Horizontal lateral lamella as a risk factor for iatrogenic cerebrospinal fluid leak. Clinical retrospective evaluation of 24 cases.

BACKGROUND: Several authors highlighted the limitations of the Keros classification system in predicting intracranial entry risk. Recently, our group proposed a new classification system based on the angle formed between the lateral lamella of the cribriform plate (LLCP) and the continuation of an horizontal plane passing through the cribriform plate (Gera classification). The aim of this study was to analyze whether the risk of iatrogenic cerebrospinal fluid leak (CSF-L) was better predicted by Keros or Gera classification. METHODOLOGY: The pre-operative CT scans of 24 patients (CSF-L group) who suffered from iatrogenic CSF-L during endoscopic sinus surgery (ESS) were compared to those obtained from a group of 100 patients who underwent uneventful ESS (control group). The skull base measurements as well as the distribution of Keros and Gera classes in the 2 groups were analyzed. RESULTS: No difference in the distribution of Keros classes or in the depth of the cribriform plate between CSF-L and control group were demonstrated. On the contrary, significant differences in the distribution of Gera classes and in the degree of the angle formed by the LLCP and the continuation of the horizontal plane passing through the cribriform plate were found. In particular, according to Gera classification system, 19 out of 24 patients in the CSF-L group were considered at risk for iatrogenic CSF-L. CONCLUSIONS: Gera classification system might be more sensitive to anatomical variations associated with CSF-L than the Keros one, further suggesting the application of the former during the preoperative CT scan evaluation.

Coping with the New Era: Noise and Light Pollution, Hperactivity and Steroid Hormones. Towards an Evolutionary View of Bipolar Disorders.

Human population is increasing in immense cities with millions of inhabitants, in which life is expected to run 24 hours a day for seven days a week (24/7). Noise and light pollution are the most reported consequences, with a profound impact on sleep patterns and circadian biorhythms. Disruption of sleep and biorhythms has severe consequences on many metabolic pathways. Suppression of melatonin incretion at night and the subsequent effect on DNA methylation may increase the risk of prostate and breast cancer. A negative impact of light pollution on neurosteroids may also affect mood. People who carry the genetic risk of bipolar disorder may be at greater risk of full-blown bipolar disorder because of the impact of noise and light pollution on sleep patterns and circadian biorhythms. However, living in cities may also offers opportunities and might be selective for people with hyperthymic temperament, who may find themselves advantaged by increased energy prompted by increased stimulation produced by life in big cities. This might result in the spreading of the genetic risk of bipolar disorder in the coming decades. In this perspective the burden of poor quality of life, increased disability adjusted life years and premature mortality due to the increases of mood disorders is the negative side of a phenomenon that in its globality also shows adaptive aspects. The new lifestyle also influences those who adapt and show behaviors, reactions and responses that might resemble the disorder, but are on the adaptive side.

The structure of schizotypal personality traits: a cross-national study.

BACKGROUND: Schizotypal traits are considered a phenotypic-indicator of schizotypy, a latent personality organization reflecting a putative liability for psychosis. To date, no previous study has examined the comparability of factorial structures across samples originating from different countries and cultures. The main goal was to evaluate the factorial structure and reliability of the Schizotypal Personality Questionnaire (SPQ) scores by amalgamating data from studies conducted in 12 countries and across 21 sites. METHOD: The overall sample consisted of 27 001 participants (37.5% males, n = 4251 drawn from the general population). The mean age was 22.12 years (s.d. = 6.28, range 16-55 years). The SPQ was used. Confirmatory factor analysis (CFA) and Multilevel CFA (ML-CFA) were used to evaluate the factor structure underlying the SPQ scores. RESULTS: At the SPQ item level, the nine factor and second-order factor models showed adequate goodness-of-fit. At the SPQ subscale level, three- and four-factor models displayed better goodness-of-fit indices than other CFA models. ML-CFA showed that the intraclass correlation coefficients values were lower than 0.106. The three-factor model showed adequate goodness of fit indices in multilevel analysis. The ordinal α coefficients were high, ranging from 0.73 to 0.94 across individual samples, and from 0.84 to 0.91 for the combined sample. CONCLUSIONS: The results are consistent with the conceptual notion that schizotypal personality is a multifaceted construct and support the validity and utility of SPQ in cross-cultural research. We discuss theoretical and clinical implications of our results for diagnostic systems, psychosis models and cross-national mental health strategies.

Lateral lamella of the cribriform plate, a keystone landmark: proposal for a novel classification system.

BACKGROUND: The aim of this study is to propose a classification of the angle formed by the lateral lamella of the cribriform plate (LLCP) and the horizontal plane passing through the cribriform plate. In particular, the angle was classified into class I (over 80 degrees), class II (45 to 80 degrees, and class III (under 45 degrees) METHODOLOGY: A total of 190 computed tomography scans were retrospectively reviewed in order to obtain four sets of measurements. 1) depth of the cribriform, 2) angle, 3) length of the LLCP, 4) width of the fovea ethmoidalis. The relationship among these measurements were analyzed. RESULTS: The angle was significantly correlated with the depth of the cribriform and the length of the fovea, while it was negatively correlated with the length of the LLCP. Significant negative correlation was also found between the length of the LLCP and the width of the fovea. CONCLUSIONS: This angle classification is based on the theoretical risk of iatrogenic injuries, but it could be helpful also in clinical practice by providing indirect information on the thickness of the anterior skull base. As the angle decreases, in fact, the portion of the anterior skull base composed by the LLCP, increases.

Risk for Depression, Burnout and Low Quality of Life Among Personnel of a University Hospital in Italy is a Consequence of the Impact One Economic Crisis in the Welfare System?

BACKGROUND: Research literature suggests that burnout, depression, and a low mental quality of life (QOL) are common among health care workers. Economic crisis might have increased the burden of burnout, depression and low QOL in health care workers. OBJECTIVES: To identify depression risk, burnout levels, and quality of life in a sample of workers of an Italian university hospital. METHOD: Cross sectional study with comparison with two community surveys database results (n = 2000 and 1500, respectively). Overall, 522 workers accepted to take part in the study, representing a 78% response rate (out of 669 individuals). RESULTS: The frequency of positivity at the screener for Major Depressive Disorder among health care workers was more than double than that in the standardized community sample (33.3% vs 14.1%, p<0.0001). All professionals, except the administrative staff and technicians (i.e. those who do not have contact with patients), showed a statistically higher frequency of positivity for depressive episodes compared to the controls. Among the medical staff, the highest risk was found in the surgeon units, while the lowest one was in the laboratories. Surgeons also were those most exposed to high risk of burnout, as measured by the Maslach Burnout Inventory. CONCLUSION: Since burnout is linked to patient safety and quality of patient care, and contribute to medical errors, dedicated interventions aimed at reducing poor mental health and low quality of life in medical staff are indicated.

Cross-cultural adaptation and validation of the SNOT-22 into Italian.

The aim of this study is to evaluate the reliability and validity of the Italian SNOT-22 (I-SNOT-22). The study consisted of five phases: item generation, reliability analysis, normative data generation, validity analysis and responsiveness analysis. The item generation phase followed the five-step, cross-cultural, adaptation process of translation and back-translation. A group of 222 patients with chronic rhinosinusitis (CRS) were enrolled for the internal consistency analysis. Sixty patients completed the I-SNOT-22 twice, 2 weeks apart, for test-retest reliability analysis. A group of 119 asymptomatic subjects completed the I-SNOT-22 for normative data generation. I-SNOT-22 scores obtained by CRS patients and asymptomatic subjects were compared for validity analysis. I-SNOT-22 scores were correlated with Lund-Mackay and visual analogue scale (VAS) scores in 50 CRS patients for criterion validity analysis. Finally, I-SNOT-22 scores obtained in a group of 59 CRS patients before and after surgical treatment for CRS were compared for responsiveness analysis. All the enrolled subjects managed to complete the I-SNOT-22 without needing any assistance. Internal consistency was satisfactory (α = 0.86). Test-retest reliability was also satisfactory (ICC = 0.85). A significant difference in the I-SNOT-22 scores between the CRS patients and the asymptomatic subjects was found (p < 0.008). Positive significant correlations were found between I-SNOT-22 and VAS scores, while no significant correlations were found between I-SNOT-22 scores and Lund-Mackay scores. I-SNOT-22 scores obtained in the pre-treatment condition were significantly higher than those obtained after surgery. I-SNOT-22 is reliable, valid, responsive to changes in QOL, and recommended for clinical practice and outcome research.

The measurement invariance of schizotypy in Europe.

The short version of the Oxford-Liverpool Inventory of Feelings and Experiences (sO-LIFE) is a widely used measure assessing schizotypy. There is limited information, however, on how sO-LIFE scores compare across different countries. The main goal of the present study is to test the measurement invariance of the sO-LIFE scores in a large sample of non-clinical adolescents and young adults from four European countries (UK, Switzerland, Italy, and Spain). The scores were obtained from validated versions of the sO-LIFE in their respective languages. The sample comprised 4190 participants (M=20.87 years; SD=3.71 years). The study of the internal structure, using confirmatory factor analysis, revealed that both three (i.e., positive schizotypy, cognitive disorganisation, and introvertive anhedonia) and four-factor (i.e., positive schizotypy, cognitive disorganisation, introvertive anhedonia, and impulsive nonconformity) models fitted the data moderately well. Multi-group confirmatory factor analysis showed that the three-factor model had partial strong measurement invariance across countries. Eight items were non-invariant across samples. Significant statistical differences in the mean scores of the s-OLIFE were found by country. Reliability scores, estimated with Ordinal alpha ranged from 0.75 to 0.87. Using the Item Response Theory framework, the sO-LIFE provides more accuracy information at the medium and high end of the latent trait. The current results show further evidence in support of the psychometric proprieties of the sO-LIFE, provide new information about the cross-cultural equivalence of schizotypy and support the use of this measure to screen for psychotic-like features and liability to psychosis in general population samples from different European countries.

Aspirin delays mesothelioma growth by inhibiting HMGB1-mediated tumor progression.

High-mobility group box 1 (HMGB1) is an inflammatory molecule that has a critical role in the initiation and progression of malignant mesothelioma (MM). Aspirin (acetylsalicylic acid, ASA) is the most widely used nonsteroidal anti-inflammatory drug that reduces the incidence, metastatic potential and mortality of many inflammation-induced cancers. We hypothesized that ASA may exert anticancer properties in MM by abrogating the carcinogenic effects of HMGB1. Using HMGB1-secreting and -non-secreting human MM cell lines, we determined whether aspirin inhibited the hallmarks of HMGB1-induced MM cell growth in vitro and in vivo. Our data demonstrated that ASA and its metabolite, salicylic acid (SA), inhibit motility, migration, invasion and anchorage-independent colony formation of MM cells via a novel HMGB1-mediated mechanism. ASA/SA, at serum concentrations comparable to those achieved in humans taking therapeutic doses of aspirin, and BoxA, a specific inhibitor of HMGB1, markedly reduced MM growth in xenograft mice and significantly improved survival of treated animals. The effects of ASA and BoxA were cyclooxygenase-2 independent and were not additive, consistent with both acting via inhibition of HMGB1 activity. Our findings provide a rationale for the well documented, yet poorly understood antitumorigenic activity of aspirin, which we show proceeds via HMGB1 inhibition. Moreover, the use of BoxA appears to allow a more efficient HMGB1 targeting while eluding the known gastrointestinal side effects of ASA. Our findings are directly relevant to MM. Given the emerging importance of HMGB1 and its tumor-promoting functions in many cancer types, and of aspirin in cancer prevention and therapy, our investigation is poised to provide broadly applicable information.

The success of indirect restorations in posterior teeth: a systematic review of the literature.

AIM: Aim of the study was to evaluate the long-term reliability and effectiveness of inlays and onlays in ceramic and composite material, examining scientific studies published from 2004 to 2013. The results of this review were analyzed and compared with the important literature review proposed by Manhart in 2004. METHODS: With this review it was possible to analyze a total sample of 5858 Class I and II restorations, made in the posterior region: 5295 ceramic and 563 composite restorations in 2377 patients. Works were evaluated using USPHS, modified USPHS and CDA criteria after a mean observation period of 5.4 years (5.9 years for ceramic restorations, 2.6 for composite restorations). RESULTS: The arithmetic average of success was 94%, higher in ceramic restorations (94.9%) than composite materials (91.1%). The weighted average success rate was 95.3%, 92.8% for composite restorations and 96.3% for ceramic ones. The highest rates of success were found in ceramic restorations notwithstanding the longer observation period. CONCLUSION: Indirect restorations have a low failure rate and they prove to be an excellent choice in the treatment of both class I and II lesions. During the last 6 years, the parameters related to these restorations have improved, with a 4% increase of success.