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Legionellers' desease accounts for 1-8 % of cases of severe community-acquired pneumonia (CAP). Legionella spp. Is the causative organism that can result in respiratory failure, multi-organ dysfunction, sepsis, and death. Therefore, rapid diagnosis and efficient treatment are crucial. We report the clinical and microbiology study of a patient with community-acquired pneumonia caused by Legionella pneumophila, with fatal outcome. After death, the strain causing the infection was identified as Legionella pneumophila serogroup 1, Olda OLDA phenotype and sequence-type 1. This is the first reported case of septic shock and death associated with an isolate of these characteristics., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Agranulocytosis is a life-threatening side-effect of clozapine, the only approved drug for treatment-resistant schizophrenia. The long-term profile of this complication has not yet been well established. Here we aim to describe the risk of clozapine-induced agranulocytosis over the long term., Methods: We used the entire population of Finland to identify people diagnosed with schizophrenia or schizoaffective disorder between 1972 and 2014 and developed a Kaplan-Meier model of time to diagnosis of agranulocytosis during clozapine versus non-clozapine treatment over a 22-year observation period (1996 to 2017). Next, we developed a nested case-control model for agranulocytosis matching by sex, age, time since diagnosis, and being in the incident cohort on a 1 to 5 ratio. Various durations of use for clozapine and non-clozapine antipsychotic treatment were compared to the modal antipsychotic use duration, deriving adjusted odds ratios (aORs) in a multivariable regression model. Recurrence and lethality rates for clozapine-induced agranulocytosis were described. These data reflect on all individuals with lived experience of schizophrenia in Finland during the study time, although individuals with lived experience were not included in the design of the study., Findings: We identified 61 769 people with schizophrenia or schizoaffective disorder (14 037 individuals treated with clozapine and 47 732 individuals treated with non-clozapine antipsychotics), with a mean age of 46·67 years (IQR 34·44-57·61), of whom 30 721 (49·7%) were female and 31 048 (50·3%) were male (data on ethnicity not available). Among those, 398 individuals were diagnosed with agranulocytosis (231 individuals treated with clozapine and 167 individuals treated with non-clozapine antipsychotics), representing a cumulative incidence of agranulocytosis for 1·37% (95% CI 0·58-3·16) on clozapine and 0·13% (0·04-0·23) on non-clozapine antipsychotics. In the case (n=398) versus control (n=1987) model, the risk of clozapine-induced agranulocytosis decreased steeply over time from an aOR of 36·01 (95% CI 16·79-77·22) for less than 6 months on clozapine to 4·38 (1·86-10·34) for clozapine use of 54 months or more. Only one of 3559 individuals starting clozapine died because of clozapine-induced agranulocytosis., Interpretation: The risk of clozapine-induced agranulocytosis decreases steeply over time but might be persistently greater than that of non-clozapine antipsychotics. This long-term risk excess seems small in absolute terms compared with the known magnitude of the advantages of clozapine in relevant outcomes, including life expectancy. Given the widespread underuse of clozapine, relaxing the long-term neutrophil monitoring could favour the advantages of long-term clozapine use, including greater life expectancy, without incurring the intolerable risk of clozapine-induced agranulocytosis., Funding: Northwell Health and Sigrid Jusèlius Foundation., Competing Interests: Declaration of interests JMR has received honoraria from Teva, Karuna, and Janssen; royalties from UpToDate; and grant support from Saladax and Alkermes. JMK has received consulting fees or honoraria for lectures from Alkermes, Allergan, Boehringer Ingelheim, Cerevel, Click Therapeutics, Dainippon Sumitomo, H Lundbeck, Health Rhythms, HLS Therapeutics, Indivior, Intracellular Therapies, Janssen, Johnson and Johnson, Karuna, LB Pharmaceuticals, Merck, Minerva, Newron, Novartis, NW PharmaTech, Otsuka, Roche, Saladax, Sunovion, and Teva; grant support from Click Therapeutics, H Lundbeck, Janssen, Otsuka, Saladax, Sunovion, and Valera; and is a stockholder for Cerevel, Health Rhythms, Karuna, LB Pharmaceuticals, North Shore Therapies, and the Vanguard Research Group. JT, HT, and AT have participated in research projects funded by grants from Janssen-Cilag and Eli Lilly paid to their institution. JT has been a consultant or advisor to or has received honoraria from Eli Lilly, Evidera, Janssen-Cilag, Lundbeck, Orion, Otsuka, Mediuutiset, Sidera, and Sunovion. HT has received personal fees from Janssen-Cilag and Otsuka., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

This paper investigates the historical sources of soil-lead contamination in Santa Ana, California. Even though dangerous levels of soil-lead have been found in a wide variety of communities across the United States, public health institutions lack clarity on the historical origins of these crises. This study uses geo-spatial data collected through archival research to estimate the impact of two potential sources of lead contamination in the past -- lead-paint and leaded gasoline. It examines, through a combination of statistical and historical methods, the association between lead concentrations in contemporary soil samples and patterns in the evolution of the city's physical features, such as the growth of urbanized areas and the historical flow of traffic. We emphasize the value of historical data collected through archival research for understanding the sources of environmental lead, particularly leaded gasoline, which our study found to be the most likely and most prominent contributor to soil-lead in Santa Ana's environment. This research contributes to environmental-justice advocacy efforts to reframe lead poisoning as a systemic environmental issue and outlines the path forward to community-level remediation strategies., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Research Question: Does testosterone, either in a long or short course, before IVF increase the number of mature oocytes retrieved in poor ovarian response?, Design: Single-centre, single-blinded, randomized controlled trial. Poor ovarian response is defined according to Bologna criteria. Sixty-three participants were included and assigned to three arms: group 1 (long testosterone [n = 17]) 12.5 mg/day testosterone gel for 56 days before ovarian stimulation; group 2 (short testosterone [n = 16]) 12.5 mg/day testosterone gel for 10 days before ovarian stimulation; and group 3 (control, no intervention). Primary outcome was number of mature oocytes retrieved. Secondary outcomes included other cycle parameters (duration of stimulation, antral follicle count, number of follicles >16 mm, total oocytes retrieved and testosterone levels)., Results: The number of mature oocytes retrieved did not differ between the three groups (2.16, 2.71 and 2.91, P = 0.719, groups 1, 2 and 3, respectively). No other significant differences were found in the remaining cycle parameters, except for testosterone levels at the beginning of ovarian stimulation, which were higher in both testosterone groups and relatively higher in group 2 (1.67 and 3.03, respectively versus 0.14 control group, P = 0.01). A Poisson regression model showed no significant differences for the primary outcome (group 3 versus group 2: 0.925, 95% CI 0.572 to 1.508, P = 0.753; group 3 versus group 1: 0.873, 95% CI 0.534 to 1.426, P = 0.587)., Conclusions: The use of testosterone, even when applied for a prolonged period, does not improve the number of mature oocytes in poor ovarian response., (Copyright © 2021 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Infections with the filarial nematodes Loa loa and Mansonella perstans are among the most neglected filarial infections. L. loa is endemic in 11 countries of Central and West Africa and loiasis is estimated to affect about 20 million people. M. perstans infection is widespread in more than 30 countries of sub-Saharan Africa. Due to the difficulty in diagnosing loiasis and M. perstans mansonellosis on a clinical basis, the diagnosis of infection with L. loa and M. perstans relies on laboratory techniques. Definitive diagnosis is based on the detection, identification, and quantification of circulating microfilariae (mf) by microscopy of concentrated blood. However, this is impractical for screening purposes as it requires expert laboratory personnel, considerable blood manipulation, and is time consuming, especially for the final issue of negative result reports, which are very common in the population visited outside endemic areas. The aim of the current work is the preliminary evaluation of the performance of the in-house real-time PCR described by Ta and colleagues compared to the routine microscopic approach for the screening of filarial infections in the clinical setting outside endemic areas, using samples from patients accessing the dedicated outpatient clinics for migrants and travelers of a reference centre for tropical diseases in Northern Italy., (Copyright © 2021. Published by Elsevier B.V.)

Background: Most individuals with schizophrenia-spectrum disorders have relapses, which increase the risk of morbidity and mortality. Because non-adherence to antipsychotic maintenance treatment could affect more than half of individuals with schizophrenia-spectrum disorders, psychosis relapse can often be confounded by unnoticed treatment interruption. Research of relapse during confirmed antipsychotic exposure has basic clinical and neurobiological implications, but data are scarce. We aimed to generate reliable estimates of incidence and predictors of relapse during assured antipsychotic treatment., Methods: We did a systematic review and individual participant data (IPD) meta-analysis of clinical trials of long-acting injectable antipsychotics (LAIs) for psychosis relapse-prevention, following IPD-PRISMA guidelines. Datasets were identified by searching relevant repositories from inception to Aug 1, 2019. Each LAI group was reanalysed as a separate cohort, further identifying subcohorts of individuals with and without prospectively determined symptom remission (PSR). Summary incidence rate of relapse, incidence rate ratios (IRRs) of relapse between individuals with and without PSR, hazard ratios (HRs) of covariates on risk of relapse, and standardised mean difference (SMDs) in changes in overall functioning associated with relapse were generated by pooling results from the harmonised reanalysis of each study. This study is registered with PROSPERO, number CRD42019137439., Findings: 19 treatment cohorts consisting of 5130 individuals (2938 with PSR, 2192 without PSR), with 3959·53 observed participant-years, were meta-analysed. Pooled incidence of relapse was 22·97 per 100 participant-years (14·76 per 100 participant-years for the PSR subcohort, 31·51 per 100 participant-years for the non-PSR subcohort), with an IRR of 0·19 (95% CI 0·07 to 0·54). Relapse was associated with functional decline (overall SMD -0·76, 95% CI -1·14 to -0·37; PSR SMD -0·52, 95% CI -0·80 to -0·21; non-PSR SMD -0·72, 95% CI -1·18 to -0·26). The strongest predictor of relapse was tardive dyskinesia at treatment onset (HR 2·39, 95% CI 1·05 to 5·42)., Interpretation: Despite the established efficacy of antipsychotics in preventing relapse, these data indicate that these drugs might not prevent subsequent exacerbations for a proportion of individuals whose illness is stabilised on continuous antipsychotic treatment. Tardive dyskinesia in particular might have pathophysiological implications for relapse., Funding: Northwell Health., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Ictal asystole can appear in patients with focal epilepsy, even in early phases. We present our experience of 7 cases, remarking the electrocardiographic characteristics, the role of apnea, treatment and long-term evolution. Awareness of this entity and collaboration between neurologists and cardiologists are essential for a correct diagnosis and management., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Human filariae are vector-borne parasites and the causative agents of various diseases, including human onchocerciasis and lymphatic filariasis. Onchocerciasis causes a spectrum of cutaneous and ophthalmologic manifestations (including blindness) and has long been a major public health problem in Bioko Island (Equatorial Guinea). Bioko Island has been included in the WHO's Onchocerciasis Control Program since 1987. In Bioko Island, the specificity and sensitivity of clinical Onchocerca volvulus diagnosis is key. The objective of this work was to update onchocerciasis elimination progress in Bioko Island, after 18 years of mass ivermectin intervention, and the general filariasis situation through a rapid and accurate molecular method. A cross-sectional study was conducted in Bioko Island from mid-January to mid-February 2014. A total of 543 subjects were included in the study. Whole blood and one skin snip (from lumbar regions) were analysed with a real time PCR assay. Two other skin biopsies were analysed by an expert microscopist. All positive samples were confirmed by sequencing. Traditional microscopic examination of the skin biopsies failed to detect any microfilariae. However, 11 (2.03%) infections were detected using PCR assay, including one O. volvulus, two Mansonella streptocerca, seven Mansonella perstans and one Loa loa infections. PCR assays in blood detected 52 filariae-positive individuals (9.6%) which harboured M. perstans or L. loa. The low prevalence of O. volvulus confirms the success of the Onchocerciasis Control Programme and suggests that Mass Drug Administration in Bioko Island can be interrupted in the near future. The very high prevalence of M. perstans found in skin snips assays raises doubts about the reliability of microscope-based diagnosis of O. volvulus infections., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Study Objective: To compare operative and postoperative results of ovarian cortex retrieval by conventional laparoscopy (1cm umbilical site and 3 accessory 5-mm-reusable working ports) (HASS) versus single site laparoscopy (SSL)., Design: Prospective cohort study., Setting: Fertility Preservation Programme at La Fe University Hospital-University of Valencia, Valencia, Spain, 2011 to 2012. Fertility Preservation Programme at La Fe University Hospital of Valencia, Valencia, Spain., Patients: Twenty-one patients with cancer (breast cancer: n = 17; Hodgkin's lymphoma: n = 3; and non-Hodgkin's lymphoma: n = 1)., Intervention: Ovarian cortex retrieval either by conventional laparoscopy using an umbilical Hasson port and 3 accessory ports (HASS group: n = 11) or by SSL (SSL group: n = 10)., Measurements and Main Results: Operative length, blood loss, postoperative pain (visual analog scale for pain at 6, 24, and 48 hours), need of additional analgesia, quality of life (European Quality of Life-5 Dimensions), cosmesis of the scar, and patient's self-perception were assessed at 24 and 48 hours and 3 months after surgery. Baseline characteristics were similar between groups. Estimated blood loss, operative length, and postoperative pain did not differ between groups. The start of chemotherapy was not delayed in either group, and cosmesis and image self-perception were also similar., Conclusion: The SSL approach can be considered a safe option compared with the classic multisite approach., (Copyright © 2015 AAGL. Published by Elsevier Inc. All rights reserved.)

Cryptosporidium spp. and microsporidia are opportunistic parasites affecting a wide range of hosts in which they can be potentially life threatening in immunocompromised individuals. Diagnosis usually relies on the identification of the stained Cryptosporidium oocyst or microsporidial spores, but these methods lack sensitivity and require highly trained technicians to perform and interpret the results. Molecular diagnosis offers an alternative with both superior sensitivity and specificity as compared to microscopy. Although replacing microscopy with nucleic acid based methods is hampered by the higher costs, in particular in developing countries, multiplexing the detection of more than one parasite in a single test has been found to be very effective and would decrease the cost of the test without the need for new equipment, as it would be the case for quantitative PCR. The method shown in this report for the simultaneous detection of Cryptosporidium spp., Enterocytozoon bieneusi and Encephalitozoon intestinalis by multiplex nested PCR, has proved to have several advantages versus microscopy such as higher sensitivity and specificity, low subjectivity and a minimal need for specialist's training to interpret the results. The present multiplex assay can fill an important gap to identify other possible causative agents of several diarrheal diseases which until present remain undiagnosed and can improve the epidemiology of the disease with a more reliable detection method., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Aims: Antioxidant system abnormalities have been associated with ethanol consumption. This study examines the effects of chronic ethanol consumption on oxidative balance, including selenium (Se) levels in alcoholic patients with or without liver disease, and if these measurements could be indicative of liver disease., Main Methods: Serum Se levels, antioxidant enzymes' activities, malondialdehyde (MDA) and protein carbonyl (PC) were determined in three groups of patients: alcoholics without liver disease, alcoholics with liver disease, and non-alcoholics with liver disease; and in healthy volunteers., Key Findings: Serum Se levels were lower in alcoholic patients and in patients affected by liver disease and especially lower in the alcoholic liver disease group. These values were correlated with the activity of glutathione peroxidase (GPx), the antioxidant selenoprotein. The antioxidant activities of the glutathione reductase (GR) and superoxide dismutase (SOD) were also lower in the three non-healthy groups. However, GR activity decreased and SOD activity increased in the non-alcoholic liver disease group versus alcoholic groups. Higher concentrations of PC in serum were found in non-healthy groups and were higher in alcoholic patients who also showed higher MDA levels. The highest MDA and PC levels were found in the alcoholic liver disease group., Significance: We conclude that serum Se levels are drastically decreased in alcoholic liver disease patients, showing that this element has a direct correlation with GPx activity, and lipid oxidation, suggesting that the serum Se/MDA ratio could be an indicator of hepatic damage caused by alcohol consumption, and pointing to Se as a possible antioxidant therapy., (© 2013.)

Fructo-oligosaccharides (FOSs) of a six year old agave plant variety, Agave tequilana, were isolated and fractionated by 2D preparative chromatography (SEC and rpHPLC). Structural analyses of different FOS-fractions were performed by reductive methylation analysis connected to GC/FID identification and NMR-analysis. FOSs from leaves (d.p. 3-8) contain single α-d-Glcp residues as well in terminal as internal position, however (2→1)-linked β-d-Fruf residues only. FOSs from stem, however, contain as well (2→1)- and (2→6)-linked β-d-Fruf residues with branched oligomeric repeating units. These characteristics indicate an enzymatically catalyzed metabolic regulation for the biosynthesis and transformation of fructans in A. tequilana which strongly depends on location and transport activities., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Several studies show the relationship between patient satisfaction and quality of health services and also between disabling conditions and healthcare access, but none sufficiently analyze the factors that contribute to satisfaction among patients with disabilities., Objective/hypotheses: The primary aim of this paper is to quantify the impact of social factors, perceived health status and access on satisfaction with healthcare services among Spanish people with disabilities., Methods: This paper uses data from the European Health Survey 2009 to construct latent variables related to satisfaction, use and health status among Spanish patients with disabilities. Next, partial least squares path modeling is used for quantifying the effects of certain social factors, service use, and health status on patient satisfaction with received healthcare services., Results: Satisfaction with healthcare services among people with disabilities is correlated (Nagelkerke R(2) of 0.175) with certain demographic factors (age, gender and town size), assistance support and patient use of these services. Education level and income were not found to have significant effects., Conclusions: People with disabilities generally show a high level of satisfaction with healthcare services, influenced by a positive valuation of the differentiated use given their specific care needs. Subjective aspects of care have a notable influence, linked with the perception of the person's own state of health and emotional status, on these positive valuations; patients' individual perceptions can reduce care needs and the use patients make of healthcare services and tend to increase their level of satisfaction with these services when they do seek them., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Exposure of human peripheral blood monocytes to free arachidonic acid (AA) results in the rapid induction of lipid droplet (LD) formation by these cells. This effect appears specific for AA in that it is not mimicked by other fatty acids, whether saturated or unsaturated. LDs are formed by two different routes: (i) the direct entry of AA into triacylglycerol and (ii) activation of intracellular signaling, leading to increased triacylglycerol and cholesteryl ester formation utilizing fatty acids coming from the de novo biosynthetic route. Both routes can be dissociated by the arachidonyl-CoA synthetase inhibitor triacsin C, which prevents the former but not the latter. LD formation by AA-induced signaling predominates, accounting for 60-70% of total LD formation, and can be completely inhibited by selective inhibition of the group IVA cytosolic phospholipase A(2)α (cPLA(2)α), pointing out this enzyme as a key regulator of AA-induced signaling. LD formation in AA-treated monocytes can also be blocked by the combined inhibition of the mitogen-activated protein kinase family members p38 and JNK, which correlates with inhibition of cPLA(2)α activation by phosphorylation. Collectively, these results suggest that concomitant activation of p38 and JNK by AA cooperate to activate cPLA(2)α, which is in turn required for LD formation possibly by facilitating biogenesis of this organelle, not by regulating neutral lipid synthesis.

Giardia intestinalis (G. intestinalis) is a flagellate parasite which has been considered the most common protozoan infecting human. Molecular techniques are of great value in studying the taxonomy, the zoonotic potential of animal isolates and the correlation between the genetic variability of the parasite and the range of clinical symptoms observed in humans. The present work aims at genotyping G. intestinalis isolates from Egypt using molecular techniques. PCR targeting the β-giardin locus, RFLP and sequencing were applied to 12 microscopically positive and 3 microscopically negative samples (which were positive by real time PCR targeting SSUr DNA). Two other loci, triose phosphate isomerase (TPI) gene and glutamate dehydrogenase (GDH) gene PCR and RFLP were also applied to all study isolates. The most frequent genotype was Assemblage B (13 out of 15), while Assemblage A and C were present in one sample each. This is the first report on zoonotic transmission of Assemblage C (dog genotype) to human in Egypt. Sequencing of the Assemblage B isolates revealed new subgenotypes with consistent mutations at specific positions, some of which were not characterized previously. The results shed light on the possibility that G. intestinalis can infect humans through a zoonotic route and open the door to wider investigations using different genetic loci to genotype Giardia isolates., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

The prognosis for patients with ventricular arrhythmias has improved dramatically with the aid of implantable cardioverter-defibrillators (ICDs). Although infection is a serious complication that frequently causes dysfunction and loss of ICDs, the frequency, predisposing risk-factors, and clinical and microbiological features are only partially understood. This study describes a retrospective review of 423 procedures in 278 patients with ICD primary implants and replacements performed at a tertiary-care hospital. Generators were placed in either a pectoral (68%) or abdominal (32%) site, and electrodes were placed transvenously in 97% of the patients. Most (95%) interventions were performed in a one-stage procedure. Infection developed with ten (2.4%) implanted devices. Four cases occurred within 30 days of surgery ('early infections') and six occurred > 1 month after surgery ('late infections'). In univariate analysis, factors associated with the development of an early infection were: two-stage surgery, a sub-costal approach, and abdominal generator placement. In patients with late infections, a significant association was found with trauma or decubitus ulcer in the generator area. Infection presented with local signs without systemic complications. Seven of the ten patients required complete removal of the system.