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Objectives: The Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE‐BD) project pools archival datasets on older age bipolar disorder (OABD). An initial Wave 1 (W1; n = 1369) analysis found both manic and depressive symptoms reduced among older patients. To replicate this finding, we gathered an independent Wave 2 (W2; n = 1232, mean ± standard deviation age 47.2 ± 13.5, 65% women, 49% aged over 50) dataset. Design/Methods: Using mixed models with random effects for cohort, we examined associations between BD symptoms, somatic burden and age and the contribution of these to functioning in W2 and the combined W1 + W2 sample (n = 2601). Results: Compared to W1, the W2 sample was younger (p < 0.001), less educated (p < 0.001), more symptomatic (p < 0.001), lower functioning (p < 0.001) and had fewer somatic conditions (p < 0.001). In the full W2, older individuals had reduced manic symptom severity, but age was not associated with depression severity. Age was not associated with functioning in W2. More severe BD symptoms (mania p ≤ 0.001, depression p ≤ 0.001) were associated with worse functioning. Older age was significantly associated with higher somatic burden in the W2 and the W1 + W2 samples, but this burden was not associated with poorer functioning. Conclusions: In a large, independent sample, older age was associated with less severe mania and more somatic burden (consistent with previous findings), but there was no association of depression with age (different from previous findings). Similar to previous findings, worse BD symptom severity was associated with worse functioning, emphasizing the need for symptom relief in OABD to promote better functioning. Key points: With the global population of older adults increasing rapidly, it is important to understand how older adults with bipolar disorder (BD) differ from younger adults.This replication analysis using a large global dataset focused on older‐age bipolar disorder (OABD) and examined associations of older age, BD symptoms, somatic burden and functioning.Older age was associated with less severe mania and more somatic burden but there was no association of depression with age.Worse BD symptom severity was associated with worse functioning, emphasizing the need for symptom relief in OABD to promote better functioning. [ABSTRACT FROM AUTHOR]

Familial Renal Glucosuria (FRG) is a co‐dominantly inherited trait characterized by orthoglycaemic glucosuria. From 2003 to 2015 we have reported several cohorts validating SLC5A2 (16p11.2), encoding SGLT2 (Na+/glucose cotransporter family member 2), as the gene responsible for FRG. The aim of this work was to validate the variants identified in our extended FRG cohort of published, as well more recent unreported cases, according to the ACMG‐AMP 2015 criteria. Forty‐six variants were evaluated, including 16 novel alleles first described in this study. All are rare, ultra‐rare or absent from population databases and most are missense changes. According to the ACMG‐AMP standards, only 74% of the variants were classified as P/LP. The lack of descriptions of unrelated patients with similar variants or failing to test additional affected family members, averted a conclusion for pathogenicity in the alleles that scored VUS, highlighting the importance of both family testing and variant reporting. Finally, the cryo‐EM structure of the hSGLT2–MAP17 complex in the empagliflozin‐bound state improved the ACMG‐AMP pathogenicity score by identifying critical/functional protein domains. [ABSTRACT FROM AUTHOR]

Objectives: Despite the importance of psychosocial functioning impairment in Bipolar Disorder (BD), its role among Older Adults with BD (OABD) is not well known. The development of guidelines for the assessment of psychosocial functioning helps to facilitate a better understanding of OABD and can lead to better tailored interventions to improve the clinical outcomes of this population. Methods: Through a series of virtual meetings, experts from eight countries in the International Society of Bipolar Disorder (ISBD) on OABD task force developed recommendations for the assessment of psychosocial functioning. Results: We present (1) a conceptualization of functioning in OABD and differences compared with younger patients; (2) factors related to functioning in OABD; (3) current measures of functioning in OABD and their strengths and limitations; and, (4) other potential sources of information to assess functioning. Conclusions: The task force created recommendations for assessing functioning in OABD. Current instruments are limited, so measures specifically designed for OABD, such as the validated FAST‐O scale, should be more widely adopted. Following the proposed recommendations for assessment can improve research and clinical care in OABD and potentially lead to better treatment outcomes. [ABSTRACT FROM AUTHOR]

In recent years, bacterial resistance to traditional drugs has increased, and the need to find new effective antibiotics to treat infections caused by multidrug‐resistant bacteria has consequently become more important. The current study aimed to evaluate the potentiation of antibiotic activity and efflux pumps inhibition by (2E)‐1‐(4‐aminophenyl)‐3‐(4‐fluorophenyl)prop‐2‐en‐1‐one (PA‐Fluorine) against the standard and resistant bacterial strains of Staphylococcus aureus and Escherichia coli. The association between PA‐Fluorine and ampicillin reduced the minimum inhibitory concentration (MIC), showing a synergistic effect against S. aureus. For E. coli, PA‐Fluorine did not show any significant results when associated with ampicillin. Ciprofloxacin and chlorpromazine showed synergy with PA‐Fluorine on the two studied strains. An efflux pump mechanism was involved in the mechanism of action of chlorpromazine, norfloxacin, and ethidium bromide. PA‐Fluorine synergistically modulated norfloxacin and bromide. It was thus concluded that PA‐Fluorine has the potential to enhance antibacterial activity when combined with antibiotics. Molecular docking studies showed the effect of intermolecular interactions of PA‐Fluorine on the NorA and MepA efflux pumps. Physicochemical and pharmacokinetic properties were also obtained by ADMET studies for this chalcone, which presents be a strong candidate as an efflux pump inhibitor. [ABSTRACT FROM AUTHOR]

Summary: Background: Targeting histological remission or response in Crohn's disease (CD) is not recommended in clinical practice guidelines or as an outcome in clinical trials due to uncertainties regarding index validity and prognostic relevance. Aims: To conduct a modified RAND/University of California Los Angeles appropriateness process with the goal of producing a framework to standardise histological assessment of CD activity in clinical trials. Methods: A total of 115 statements generated from literature review and expert opinion were rated on a scale of 1‐9 by a panel of 11 histopathologists and 6 gastroenterologists. Statements were classified as inappropriate, uncertain or appropriate based upon the median panel rating and degree of disagreement. Results: The panellists considered it important to measure histological activity in clinical trials to determine efficacy and that absence of neutrophilic inflammation is an appropriate histological target. They were uncertain whether the Global Histological Activity Score was an appropriate instrument for measuring histological activity. The Geboes Score and Robarts Histopathology Index were considered appropriate. Two biopsies from five segments should be biopsied, and the colon and the ileum should be analysed separately for all indices. Endoscopic mucosal appearance should guide biopsy procurement site with biopsies taken from the ulcer edge, or the most macroscopically inflamed area in the absence of ulcers. Conclusion: We evaluated the appropriateness of items for assessing histological disease activity in CD clinical trials. These items will be used to develop a novel histological index. [ABSTRACT FROM AUTHOR]

Carvacrol is a monoterpene present in the essential oil of a number of plants and has been widely used in traditional medicine because it is considered to have a range of therapeutic effects including in relation to respiratory disease. To conduct a systematic review and meta-analysis to assess the anti-inflammatory and antioxidant activities of carvacrol when used in the treatment of respiratory disorders. A comprehensive literature search using Scopus, MEDLINE-PubMed, Cochrane and Web of Science was undertaken. Papers related to the anti-inflammatory or antioxidant properties of carvacrol in the treatment of an injury in the respiratory system in in vivo studies and published in the period up to and including August 2019. A total of 152 studies were initially identified, with only 17 meeting the inclusion criteria. Five of the studies were performed in humans, and 12 were performed in rodents. Among the 17 studies included in the systematic review, we performed the meta-analysis with nine of the studies with animals. Carvacrol had a positive effect on the reduction of interleukin (IL)-1β, IL-4, IL-8 and malondialdehyde (MDA); however, the analysis indicated that carvacrol had no effect on IL-6 and tumor necrosis factor alpha (TNF-α), probably due to the methodological quality of the studies and their heterogeneity. Current evidence supports the antioxidant and anti-inflammatory effects of carvacrol, but its relationship with the reduction of some inflammatory mediators in animals with lung injury needs further elucidation. [ABSTRACT FROM AUTHOR]

Objective: We examined brain volume and atrophy in individuals with major depressive disorder (MDD) without dementia that were referred to a large autopsy service. We also examined potential risk factors for brain atrophy, including demographics and clinical variables.Methods: In this study, 1373 participants (787 male) aged 50 years or older who died from natural causes were included. Participants with no reliable informant, with cognitive impairment or dementia, with a medical history of severe chronic disease, or with prolonged agonal state were excluded. Presence of MDD at least once in their lifetime was defined according to the Structured Clinical Interview for DSM. Brain volume was measured immediately after removal from the skull.Results: Mean age at death was 68.6 ± 11.6, and MDD was present in 185 (14%) individuals. Smaller brain volume was associated with older age (p < 0.001), lower education (years; p < 0.001), hypertension (p = 0.001), diabetes (p = 0.006), and female gender (p < 0.001). In the multivariate analysis adjusted for sociodemographics and cardiovascular risk factors, smaller brain volume was not associated with major depression (β = -0.86, 95% CI = -26.50 to 24.77, p = 0.95).Conclusions: In this large autopsy study of older adults, MDD was not associated with smaller brain volumes. Regardless of the presence of MDD, in this sample of older adults without dementia, we found that smaller brain volumes were associated with risk factors for brain neurodegeneration such as older age, diabetes, hypertension, and lower education. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background There are few studies addressing caregivers of bipolar disorder (BD) patients, especially patients who are older adults with an increased need for care, often given by a relative. The aim of this study was to describe which factors increase caregiver burden among caregivers of elderly BD outpatients. Methods Patients were older than 60 years and met the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, criteria for BD. They were evaluated for current mood, cognitive and other neuropsychiatric symptoms, functionality, medical comorbidities, quality of life, years since BD diagnosis, and number of psychiatric admissions. The caregiver who spent the greatest time with each patient was evaluated with the Zarit Caregiver Burden Interview. The caregivers' global health, mood symptoms, quality of life, and tasks performed for the patient were also assessed. Results Thirty-six BD patients and their caregivers were assessed. The Zarit Caregiver Burden Interview was positively correlated with patients' neuropsychiatric symptoms ( r = 0.508, P = 0.002) and functional impairment ( r = 0.466, P = 0.004). The Zarit Caregiver Burden Interview was also correlated with caregivers' own depression ( r = 0.576, P < 0.001), anxiety ( r = 0.360, P = 0.031), quality of life ( r = −0.406, P = 0.014), medical comorbidities ( r = 0.387, P = 0.020), and number of tasks that they completed for the patient ( r = 0.480, P = 0.003). Conclusions In this group of elderly BD patients, caregiver burden was more associated with symptoms frequently seen in others diseases as in dementia than with depressive, manic, or anxiety symptoms, which are often used as treatment outcomes measures goals in BD. Potential treatable and modifiable factors associated with caregiver burden could be caregivers' depression, anxiety, and medical comorbidities, as well as support for caregivers in terms of services and social relationships. [ABSTRACT FROM AUTHOR]

Neuropsychiatric symptoms in community-dwelling older Brazilians with mild cognitive impairment and dementia Neuropsychiatric symptoms in Brazilians with mild cognitive impairment and dementia. Dear Dr. Liana Apostolova, Neuropsychiatric symptoms are common preceding and in the course of dementia and are the cause of significant burden to patients and caregivers alike.[1] Considering that most people with dementia live in low- to middle-income countries,[2] it is critical to understand the frequency and distribution of these symptoms across dementia stages in these countries. [Extracted from the article]

Unfortunately, the diagnosis of BD still relies solely on clinical evaluation, in contrast with a wide range of biomarkers available for detecting neurodegenerative disorders, including LBD and FTD. Despite being the third most frequent cause of dementia confirmed by neuropathological studies,2 LBD can be often overlooked by psychiatrists, as Khosravi's study also pointed out, because some of its core symptoms may be attributable as either symptoms of BD or side effects of BD treatments to which patients can be more susceptible as they get older. LBD includes dementia with Lewy bodies in which dementia develops early in the course of the disease and Parkinson's disease dementia, a dementia that has later developed in someone with established Parkinson's disease. [Extracted from the article]

The Brazilian oil industry has gained new momentum after the discovery of large oil reserves in deep under-water. Numerous investments in the oil production chain are expected to support the scale of this operation. Given this context, the use of a decision support system (DSS), which encompasses the complexity of the oil supply chain to support investment decisions, becomes crucial. This paper proposes a DSS that is based on a mixed-integer linear programming (MILP) model that allows the evaluation of different investment alternatives in logistics networks, such as expanding the capacity for transport, handling, and/or storage. Additionally, the DSS is composed of a database structure, business intelligence environment, and graphical visualization tool. The features of the proposed system were evaluated in two case studies. The first case study assesses the synergies between two projects: specifically the expansion of the berthing capacity of vessels in a marine terminal, and the increase in the transport capacity of the pipeline that connects the marine terminal to a distribution base. The second case study evaluates the dependency of the investment in sections of a pipeline that connects a refinery to several distribution bases. These case studies demonstrate the potential use of a DSS that currently optimizes investments in the Brazilian petroleum supply chain. [ABSTRACT FROM AUTHOR]

The production of reactive oxygen species ( ROS) within immune cell phagosomes is critical for antimicrobial activity and for correct antigen processing, and influences signaling pathways that direct host responses to infection and inflammation. Because excess oxidants can cause tissue damage and oxidative stress, phagocytes must precisely control both the location and timing of NADPH oxidase activity. How differential regulation is achieved at phagosomes is not well understood. Recent studies have revealed that the PI(3)P phosphoinositide plays an important role in locally boosting phagosomal NADPH oxidase activity through its binding to the p40 phox NADPH oxidase subunit. Furthermore, phox subunit dynamics at phagosomes may regulate the timing of the oxidative burst. Novel elements regulating catalytic core trafficking include Rab27 and SNAP-23. In addition to trafficking events, the activity of the electrogenic oxidase is also governed by ionic fluxes, which are constrained at phagosomes owing to low intraphagosomal volume and dynamic display of channels, transporters, and pumps. New insights on the interdependence of phagosomal pH and ROS have been recently elucidated, and chloride channels important for microbicidal functions, including CFTR, and CLIC family channels, have been identified. Finally, periphagosomal calcium microdomains and calcium-dependent S100A8/9 protein recruitment may help fine-tune spatiotemporal regulation of NADPH oxidase activation for an effective immune response. [ABSTRACT FROM AUTHOR]

Objective: To identify the CAMCOG sub-items that best contribute for the identification of patients with mild cognitive impairment (MCI) and incipient Alzheimer’s disease (AD) in clinical practice. Methods: Cross-sectional assessment of 272 older adults (98 MCI, 82 AD, and 92 controls) with a standardized neuropsychological battery and the CAMCOG schedule. Backward logistic regression analysis with diagnosis (MCI and controls) as dependent variable and the sub-items of the CAMCOG as independent variable was carried out to determine the CAMCOG sub-items that predicted the diagnosis of MCI. Results: Lower scores on Language, Memory, Praxis, and Calculation CAMCOG sub-items were significantly associated with the diagnosis of MCI. A composite score obtained by the sum of these scores significantly discriminated MCI patients from comparison groups. This reduced version of the CAMCOG showed similar diagnostic accuracy than the original schedule for the identification of patients with MCI as compared to controls (AUC=0.80±0.03 for the reduced CAMCOG; AUC=0.79±0.03 for the original CAMCOG). Conclusion: This reduced version of the CAMCOG had similar diagnostic properties as the original CAMCOG and was faster and easier to administer, rendering it more suitable for the screening of subtle cognitive deficits in general clinical practice. Copyright # 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background The CAMCOG is a brief neuropsychological battery designed to assess global cognitive function and ascertain the impairments that are required for the diagnosis of dementia. To date, the cut-off scores for mild cognitive impairment (MCI) have not been determined. Given the need for an earlier diagnosis of mild dementia, new cut-off values are also necessary, taking into account cultural and educational effects. Methods One hundred and fifty-seven older adults (mean age: 69.6 ± 7.4 years) with 8 or more years of formal education (mean years of schooling 14.2 ± 3.8) attending a memory clinic at the Institute of Psychiatry University of Sao Paulo were included. Subjects were divided into three groups according to their cognitive status, established through clinical and neuropsychological assessment: normal controls, n = 62; MCI, n = 65; and mild or moderate dementia, n = 30. ROC curve analyses were performed for dementia vs controls, MCI vs controls and MCI vs dementia. Results The cut-off values were: 92/93 for dementia vs controls (AUC = 0.99: sensitivity: 100%, specificity: 95%); 95/96 for MCI vs controls (AUC = 0.83, sensitivity: 64%, specificity: 88%), and 85/86 for MCI vs dementia (AUC = 0.91, sensitivity: 81%, specificity: 88%). The total CAMCOG score was more accurate than its subtests Mini-mental State Examination, Verbal Fluency Test and Clock Drawing Test when used separately. Conclusions The CAMCOG discriminated controls and MCI from demented patients, but was less accurate to discriminate MCI from controls. The best cut-off value to differentiate controls and demented was higher than suggested in the original publication, probably because only cases of mild to moderate dementia were included. This is important given the need for a diagnostic at earlier stages of Alzheimer's disease. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Stenotrophomonas maltophilia is a Gram-negative bacillus, which is an extremely rare cause of meningitis. To our knowledge, there are only five previous pediatrics cases. Here, we describe the case of a 4-year-old boy who developed meningitis associated with this organism, after several neurosurgical procedures and previous treatment with a broad-spectrum antibiotic. He was treated successfully with a combination of trimethoprim-sulfamethoxazole, ceftazidime and levofloxacin. Stenotrophomonas maltophilia should be considered as a potential cause of meningitis, especially among severely debilitated or immunosuppressed patients. Antimicrobial therapy is complicated by the high resistance of the organism to multiple antibiotics. [ABSTRACT FROM AUTHOR]