Investigating strontium isotope linkage between biominerals (uroliths), drinking water and environmental matrices

: This study presents the mineralogy and strontium isotope ratio (87Sr/86Sr) of 21 pathological biominerals (bladder and kidney stones) collected from patients admitted between 2018 and 2020 at the Department of Urology of the San Pio Hospital (Benevento, southern Italy). Urinary stones belong to the calcium oxalate, purine or calcium phosphate mineralogy types. Their corresponding 87Sr/86Sr range from 0.707607 for an uricite sample to 0.709970 for a weddellite one, and seem to be partly discriminated based on the mineralogy. The comparison with the isotope characteristics of 38 representative Italian bottled and tap drinking waters show a general overlap in 87Sr/86Sr with the biominerals. However, on a smaller geographic area (Campania Region), we observe small 87Sr/86Sr differences between the biominerals and local waters. This may be explained by external Sr inputs for example from agriculture practices, inhaled aerosols (i.e., particulate matter), animal manure and sewage, non-regional foods. Nevertheless, biominerals of patients that stated to drink and eat local water/wines and foods every day exhibited a narrower 87Sr/86Sr range roughly matching the typical isotope ratios of local geological materials and waters, as well as those of archaeological biominerals from the same area. Finally, we conclude that the strontium isotope signature of urinary stones may reflect that of the environmental matrices surrounding patients, but future investigations are recommended to ultimately establish the potential for pathological biominerals as reliable biomonitoring proxies, taking into the account the contribution of the external sources of Sr

Walk your talk: Real-world adherence to guidelines on the use of MRI in multiple sclerosis

(1) Although guidelines about the use of MRI sequences for Multiple Sclerosis (MS) diagnosis and follow-up are available, variability in acquisition protocols is not uncommon in everyday clinical practice. The aim of this study was to evaluate the real-world application of MS imaging guidelines in different settings to clarify the level of adherence to these guidelines. (2) Via an on-line anonymous survey, neuroradiologists (NR) were asked about MRI protocols and parameters routinely acquired when MS patients are evaluated in their center, both at diagnosis and followup. Furthermore, data about report content and personal opinions about emerging neuroimaging markers were also retrieved. (3) A total of 46 participants were included, mostly working in a hospital or university hospital (80.4%) and with more than 10 years of experience (47.9%). We found a relatively good adherence to the suggested MRI protocols regarding the use of T2-weighted sequences, although almost 10% of the participants routinely acquired 2D sequences with a slice thickness superior to 3 mm. On the other hand, a wider degree of heterogeneity was found regarding gadolinium administration, almost routinely performed at follow-up examination (87.0% of cases) in contrast with the current guidelines, as well as a low use of a standardized reporting system (17.4% of cases). (4) Although the MS community is getting closer to a standardization of MRI protocols, there is still a relatively wide heterogeneity among NR, with particular reference to contrast administration, which must be overcome to guarantee an adequate quality of patients’ care in MS

Walk your talk: Real-world adherence to guidelines on the use of MRI in multiple sclerosis

(1) Although guidelines about the use of MRI sequences for Multiple Sclerosis (MS) diagnosis and follow-up are available, variability in acquisition protocols is not uncommon in everyday clinical practice. The aim of this study was to evaluate the real-world application of MS imaging guidelines in different settings to clarify the level of adherence to these guidelines. (2) Via an on-line anonymous survey, neuroradiologists (NR) were asked about MRI protocols and parameters routinely acquired when MS patients are evaluated in their center, both at diagnosis and followup. Furthermore, data about report content and personal opinions about emerging neuroimaging markers were also retrieved. (3) A total of 46 participants were included, mostly working in a hospital or university hospital (80.4%) and with more than 10 years of experience (47.9%). We found a relatively good adherence to the suggested MRI protocols regarding the use of T2-weighted sequences, although almost 10% of the participants routinely acquired 2D sequences with a slice thickness superior to 3 mm. On the other hand, a wider degree of heterogeneity was found regarding gadolinium administration, almost routinely performed at follow-up examination (87.0% of cases) in contrast with the current guidelines, as well as a low use of a standardized reporting system (17.4% of cases). (4) Although the MS community is getting closer to a standardization of MRI protocols, there is still a relatively wide heterogeneity among NR, with particular reference to contrast administration, which must be overcome to guarantee an adequate quality of patients' care in MS

Whole Genome Sequence Dataset of Mycobacterium tuberculosis Strains from Patients of Campania Region

: Tuberculosis (TB) is one of the deadliest infectious disorders in the world. To effectively TB manage, an essential step is to gain insight into the lineage of Mycobacterium tuberculosis (MTB) and the distribution of drug resistance. Although the Campania region is declared a cluster area for the infection, to contribute to the effort to understand TB evolution and transmission, still poorly known, we have generated a dataset of 159 genomes of MTB strains, from Campania region collected during 2018-2021, obtained from the analysis of whole genome sequence. The results show that the most frequent MTB lineage is the 4 according for 129 strains (81.11%). Regarding drug resistance, 139 strains (87.4%) were classified as multi susceptible, while the remaining 20 (12.58%) showed drug resistance. Among the drug-resistance strains, 8 were isoniazid-resistant MTB, 4 multidrug-resistant MTB, while only one was classified as pre-extensively drug-resistant MTB. This dataset expands the existing available knowledge on drug resistance and evolution of MTB, contributing to further TB-related genomics studies to improve the management of this disease

Association of Vascular Risk Factors and Cerebrovascular Pathology With Alzheimer Disease Pathologic Changes in Individuals Without Dementia

BACKGROUND AND OBJECTIVES: Vascular risk factors (VRFs) and cerebral small vessel disease (cSVD) are common in patients with Alzheimer disease (AD). It remains unclear whether this coexistence reflects shared risk factors or a mechanistic relationship and whether vascular and amyloid pathologies have independent or synergistic influence on subsequent AD pathophysiology in preclinical stages. We investigated links between VRFs, cSVD, and amyloid levels (Aβ1-42) and their combined effect on downstream AD biomarkers, that is, CSF hyperphosphorylated tau (P-tau181), atrophy, and cognition. METHODS: This retrospective study included nondemented participants (Clinical Dementia Rating < 1) from the European Prevention of Alzheimer's Dementia (EPAD) cohort and assessed VRFs with the Framingham risk score (FRS) and cSVD features on MRI using visual scales and white matter hyperintensity volumes. After preliminary linear analysis, we used structural equation modeling (SEM) to create a “cSVD severity” latent variable and assess the direct and indirect effects of FRS and cSVD severity on Aβ1-42, P-tau181, gray matter volume (baseline and longitudinal), and cognitive performance (baseline and longitudinal). RESULTS: A total cohort of 1,592 participants were evaluated (mean age = 65.5 ± 7.4 years; 56.16% F). We observed positive associations between FRS and all cSVD features (all p < 0.05) and a negative association between FRS and Aβ1-42 (β = −0.04 ± 0.01). All cSVD features were negatively associated with CSF Aβ1-42 (all p < 0.05). Using SEM, the cSVD severity fully mediated the association between FRS and CSF Aβ1-42 (indirect effect: β = −0.03 ± 0.01), also when omitting vascular amyloid-related markers. We observed a significant indirect effect of cSVD severity on P-tau181 (indirect effect: β = 0.12 ± 0.03), baseline and longitudinal gray matter volume (indirect effect: β = −0.10 ± 0.03; β = −0.12 ± 0.05), and baseline cognitive performance (indirect effect: β = −0.16 ± 0.03) through CSF Aβ1-42. DISCUSSION: In a large nondemented population, our findings suggest that cSVD is a mediator of the relationship between VRFs and CSF Aβ1-42 and affects downstream neurodegeneration and cognitive impairment. We provide evidence of VRFs indirectly affecting the pathogenesis of AD, highlighting the importance of considering cSVD burden in memory clinics for AD risk evaluation and as an early window for intervention. These results stress the role of VRFs and cerebrovascular pathology as key biomarkers for accurate design of anti-amyloid clinical trials and offer new perspectives for patient stratification

Neurostructural subgroup in 4291 individuals with schizophrenia identified using the subtype and stage inference algorithm

Machine learning can be used to define subtypes of psychiatric conditions based on shared biological foundations of mental disorders. Here we analyzed cross-sectional brain images from 4,222 individuals with schizophrenia and 7038 healthy subjects pooled across 41 international cohorts from the ENIGMA, non-ENIGMA cohorts and public datasets. Using the Subtype and Stage Inference (SuStaIn) algorithm, we identify two distinct neurostructural subgroups by mapping the spatial and temporal ‘trajectory’ of gray matter change in schizophrenia. Subgroup 1 was characterized by an early cortical-predominant loss with enlarged striatum, whereas subgroup 2 displayed an early subcortical-predominant loss in the hippocampus, striatum and other subcortical regions. We confirmed the reproducibility of the two neurostructural subtypes across various sample sites, including Europe, North America and East Asia. This imaging-based taxonomy holds the potential to identify individuals with shared neurobiological attributes, thereby suggesting the viability of redefining existing disorder constructs based on biological factors

Structural brain abnormalities and aggressive behaviour in schizophrenia: Mega-analysis of data from 2095 patients and 2861 healthy controls via the ENIGMA consortium

BACKGROUND: Schizophrenia is associated with an increased risk of aggressive behaviour, which may partly be explained by illness-related changes in brain structure. However, previous studies have been limited by group-level analyses, small and selective samples of inpatients and long time lags between exposure and outcome. METHODS: This cross-sectional study pooled data from 20 sites participating in the international ENIGMA-Schizophrenia Working Group. Sites acquired T1-weighted and diffusion-weighted magnetic resonance imaging scans in a total of 2095 patients with schizophrenia and 2861 healthy controls. Measures of grey matter volume and white matter microstructural integrity were extracted from the scans using harmonised protocols. For each measure, normative modelling was used to calculate how much patients deviated (in z-scores) from healthy controls at the individual level. Ordinal regression models were used to estimate the associations of these deviations with concurrent aggressive behaviour (as odds ratios [ORs] with 99% confidence intervals [CIs]). Mediation analyses were performed for positive symptoms (i.e., delusions, hallucinations and disorganised thinking), impulse control and illness insight. Aggression and potential mediators were assessed with the Positive and Negative Syndrome Scale, Scale for the Assessment of Positive Symptoms or Brief Psychiatric Rating Scale. RESULTS: Aggressive behaviour was significantly associated with reductions in total cortical volume (OR [99% CI] = 0.88 [0.78, 0.98], p = .003) and global white matter integrity (OR [99% CI] = 0.72 [0.59, 0.88], p = 3.50 × 10-5) and additional reductions in dorsolateral prefrontal cortex volume (OR [99% CI] = 0.85 [0.74, 0.97], p =.002), inferior parietal lobule volume (OR [99% CI] = 0.76 [0.66, 0.87], p = 2.20 × 10-7) and internal capsule integrity (OR [99% CI] = 0.76 [0.63, 0.92], p = 2.90 × 10-4). Except for inferior parietal lobule volume, these associations were largely mediated by increased severity of positive symptoms and reduced impulse control. CONCLUSIONS: This study provides evidence that the co-occurrence of positive symptoms, poor impulse control and aggressive behaviour in schizophrenia has a neurobiological basis, which may inform the development of therapeutic interventions

Protective effect of levodropropizine against cough induced by inhalation of nebulized distilled water in patients with obstructive lung disease.

Levodropropizine is a recently developed, peripherally active antitussive agent which is widely used in clinical practice. In order to obtain further information on the spectrum of activity of this compound in experimental clinical models, a double-blind controlled study was carried out to evaluate the potential effect of the drug against cough and bronchoconstriction induced by inhalation of an ultrasonically nebulized solution of distilled water in patients with obstructive lung disease. Twenty patients were randomly divided into two groups, which received levodropropizine (60 mg t.i.d.) or placebo respectively for 7 consecutive days. Parameters evaluated at baseline and on the last day of treatment included (i) results of respiratory function tests (FEV1, IVC, FVC, TIFF, PEF, MEF75, MEF50, MEF25) performed before the stimulation test with nebulized water; (ii) total number of coughs during a 2-hour period after the stimulation test; (iii) bronchial responsiveness, quantified by calculating the volume of nebulized water required to induce a 20% reduction of FEV1 below the basal level. At pretreatment, the tussive response was very similar in the two groups. A significant decrease in number of coughs (from 34.4 +/- 8.4 at baseline to 15.6 +/- 4.9 post-treatment, p < 0.01) was observed after administration of levodropropizine, whereas placebo treatment produced no significant effect (number of coughs: 29.6 +/- 4.9 at baseline vs 24.8 +/- 9.6 post-treatment, N. S.). Bronchial responsiveness decreased significantly (compared to baseline) in both treatment groups, without any significant difference between drug and placebo. Respiratory function tests were not significantly affected by either treatment. It is concluded that levodropropizine effectively antagonizes the cough response induced by inhalation of distilled water without affecting bronchial responsiveness in patients with chronic obstructive lung disease