Use of Antipsychotic Medications and Cholinesterase Inhibitors and the Risk of Falls and Fractures: self-controlled case series

Objective: To evaluate the association between the use of antipsychotic medications and cholinesterase inhibitors, and the risk of falls and fractures in elderly patients with major neurocognitive disorders. / Design: Self-controlled case series / Setting: Taiwan’s National Health Insurance Database / Participants: 15,278 patients who were aged 65 or older, were newly prescribed antipsychotic medications and cholinesterase inhibitors, and suffered an incident fall or fracture between 2006 and 2017. Prescription records of cholinesterase inhibitors were used to confirm the diagnosis of major neurocognitive disorders since all use of cholinesterase inhibitors was subject to review by experts based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and patients’ scores of Mini-Mental State Examination. We excluded those with schizophrenia and bipolar disorder before the first prescription of cholinesterase inhibitors to ensure that antipsychotic medications were used for neuropsychiatric symptoms of major neurocognitive disorders. / Main outcome measures: We used conditional Poisson regression to derive the incidence rate ratio and the 95% confidence interval for evaluating the association between the risk of falls and fractures and different exposure periods, including cholinesterase inhibitors alone, antipsychotic medications alone, and combination, as compared with the non-exposure period for the same individual. Moreover, we defined a 14-day pre-exposure period before study drug initiation over concerns about confounding by indication. / Results: Compared with the non-exposure period (incidence rate per 100 person-years; 95% confidence interval: 8.30; 8.14 to 8.46), the highest risk of falls and fractures occurred during the pre-exposure period (52.35; 48.46 to 56.47), followed by combination (10.55; 9.98 to 11.14), antipsychotic medications alone (10.34; 9.80 to 10.89), and cholinesterase inhibitors alone (9.41; 8.98 to 9.86). Conclusions: The incidence of falls and fractures was especially high in the pre-exposure period, suggesting that factors other than the study medications, such as underlying diseases, should be taken into consideration when evaluating the association between the risk of falls and fractures, and the use of cholinesterase inhibitors and antipsychotic medications. The exposure periods were also associated with a higher risk of falls and fractures, compared with the non-exposure period, although the magnitude was much lower than during the pre-exposure period. Prevention strategies and close monitoring of the risk of falls are still necessary until there is evidence that patients have regained a steady status

The Characteristics of Seebeck Coefficient in Silicon Nanowires Manufactured by CMOS Compatible Process

Silicon nanowires are patterned down to 30 nm using complementary metal-oxide-semiconductor (CMOS) compatible process. The electrical conductivities of n-/p-leg nanowires are extracted with the variation of width. Using this structure, Seebeck coefficients are measured. The obtained maximum Seebeck coefficient values are 122 μV/K for p-leg and −94 μV/K for n-leg. The maximum attainable power factor is 0.74 mW/m K2 at room temperature

PrP is a central player in toxicity mediated by soluble aggregates of neurodegeneration-causing proteins

Neurodegenerative diseases are an enormous public health problem, affecting tens of millions of people worldwide. Nearly all of these diseases are characterized by oligomerization and fibrillization of neuronal proteins, and there is great interest in therapeutic targeting of these aggregates. Here, we show that soluble aggregates of α-synuclein and tau bind to plate-immobilized PrP in vitro and on mouse cortical neurons, and that this binding requires at least one of the same N-terminal sites at which soluble Aβ aggregates bind. Moreover, soluble aggregates of tau, α-synuclein and Aβ cause both functional (impairment of LTP) and structural (neuritic dystrophy) compromise and these deficits are absent when PrP is ablated, knocked-down, or when neurons are pre-treated with anti-PrP blocking antibodies. Using an all-human experimental paradigm involving: (1) isogenic iPSC-derived neurons expressing or lacking PRNP, and (2) aqueous extracts from brains of individuals who died with Alzheimer's disease, dementia with Lewy bodies, and Pick's disease, we demonstrate that Aβ, α-synuclein and tau are toxic to neurons in a manner that requires PrPC. These results indicate that PrP is likely to play an important role in a variety of late-life neurodegenerative diseases and that therapeutic targeting of PrP, rather than individual disease proteins, may have more benefit for conditions which involve the aggregation of more than one protein

S021-04 OA. A large-scale analysis of immunoglobulin sequences derived from plasmablasts/plasma cells in acute HIV-1 infection subjects

Background In acute HIV-1 infection (AHI) there are infectioninduced polyclonal shifts in blood and bone marrow Bcell subsets from naïve to memory cells and plasmablasts/ plasma cells (PCs) coupled with decreased numbers of naive B cells. To study the initial antibody response to HIV, we have used recombinant technology to create a database of PC antibody sequences derived from 3 early stage AHI subjects

Event Monitoring System to Classify Unexpected Events for Production Planning

[EN] Production planning prepares companies to a future production scenario. The decision process followed to obtain the production plan considers real data and estimated data of this future scenario. However, these plans can be affected by unexpected events that alter the planned scenario and in consequence, the production planning. This is especially critical when the production planning is ongoing. Thus providing information about these events can be critical to reconsider the production planning. We herein propose an event monitoring system to identify events and to classify them into different impact levels. The information obtained from this system helps to build a risk matrix, which determines the significance of the risk from the impact level and the likelihood. A prototype has been built following this proposal.This research has been carried out in the framework of the project GV/2014/010 funded by the Generalitat Valenciana (Identificacion de la informacion proporcionada por los nuevos sistemas de deteccion accesibles mediante internet en el ambito de las "sensing enterprises" para la mejora de la toma de decisiones en la planificacion de la produccion).Boza, A.; Alarcón Valero, F.; Alemany Díaz, MDM.; Cuenca, L. (2017). Event Monitoring System to Classify Unexpected Events for Production Planning. Lecture Notes in Business Information Processing. 291:140-154. https://doi.org/10.1007/978-3-319-62386-3_7S140154291Barták, R.: On the boundary of planning and scheduling: a study (1999)Buzacott, J.A., Corsten, H., Gössinger, R., Schneider, H.M.: Production Planning and Control: Basics and Concepts. 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Syst. 45(1), 104–112 (2004)Boza, A., Alemany, M.M.E., Vicens, E., Cuenca, L.: Event management in decision-making processes with decision support systems. In: 5th International Conference on Computers Communications and Control (2014)Liao, S.-H.: Expert system methodologies and applications–a decade review from 1995 to 2004. Expert Syst. Appl. 28(1), 93–103 (2005)ISO: 73: 2009: Risk management vocabulary. International Organization for Standardization (2009)Chan, F.T.S., Au, K.C., Chan, P.L.Y.: A decision support system for production scheduling in an ion plating cell. Expert Syst. Appl. 30(4), 727–738 (2006)Weinstein, L., Chung, C.-H.: Integrating maintenance and production decisions in a hierarchical production planning environment. Comput. Oper. Res. 26(10–11), 1059–1074 (1999)Poon, T.C., Choy, K.L., Chan, F.T.S., Lau, H.C.W.: A real-time production operations decision support system for solving stochastic production material demand problems. Expert Syst. 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Evaluating a cross-lagged panel model between problematic internet use and psychological distress and cross-level mediation of school administrator support on problematic internet use: the serial mediating role of psychological needs thwarting of online teaching and psychological distress

Background: To reduce the transmission of COVID-19, many teachers across the globe, including teachers in China, were required to teach online. This shift to online teaching can easily result in psychological need thwarting (PNT) of teachers' psychological basic needs (autonomy, competence, and relatedness), leaving them vulnerable to negative psychological outcomes. Resulting negative emotional state may lead to problematic internet use (PIU), which can lead to further psychological distress, forming a vicious cycle. Methods: The present study was conducted using a cross-lagged panel model (with longitudinal data) and hierarchical linear modeling (HLM) (with cross-sectional data). The aims were to investigate (i) the reciprocal relationships between two specific forms of PIU [problematic social media use (PSMU) and problematic gaming (PG)] and psychological distress among schoolteachers, and (ii) the influence of administrators' support on schoolteachers' PIU through a cross-level serial mediation model (PNT of online teaching was the first mediator and psychological distress was the second mediator affected by PNT of online teaching). Primary and secondary schoolteachers (N = 980; mean age = 34.76; 82.90% females) participated in two surveys (Time 1: mid-November 2021; Time 2: early-January 2022). Results: Results indicated that (i) high psychological distress at Time 1 was associated with increased levels of PSMU and PG at Time 2. Inversely, PG at Time 1 was associated with increased psychological distress at Time 2, although PSMU at Time 1 did not have a significant influence on psychological distress at Time 2; (ii) during Time 1, increased administrative support contributed to alleviating teachers' psychological needs thwarting of online teaching, thereby lowering their psychological distress which, in turn, resulted in a decrease in PG. Conclusion: PG had a stronger negative influence on teachers' psychological distress than PSMU. To relieve teachers' PG, administrative support can alleviate teachers' psychological needs thwarting of online teaching and psychological distress. Based on this finding, school managers must consider effective ways to support teachers during mandatory online teaching

The Waiting Time for Inter-Country Spread of Pandemic Influenza

BACKGROUND: The time delay between the start of an influenza pandemic and its subsequent initiation in other countries is highly relevant to preparedness planning. We quantify the distribution of this random time in terms of the separate components of this delay, and assess how the delay may be extended by non-pharmaceutical interventions. METHODS AND FINDINGS: The model constructed for this time delay accounts for: (i) epidemic growth in the source region, (ii) the delay until an infected individual from the source region seeks to travel to an at-risk country, (iii) the chance that infected travelers are detected by screening at exit and entry borders, (iv) the possibility of in-flight transmission, (v) the chance that an infected arrival might not initiate an epidemic, and (vi) the delay until infection in the at-risk country gathers momentum. Efforts that reduce the disease reproduction number in the source region below two and severe travel restrictions are most effective for delaying a local epidemic, and under favourable circumstances, could add several months to the delay. On the other hand, the model predicts that border screening for symptomatic infection, wearing a protective mask during travel, promoting early presentation of cases arising among arriving passengers and moderate reduction in travel volumes increase the delay only by a matter of days or weeks. Elevated in-flight transmission reduces the delay only minimally. CONCLUSIONS: The delay until an epidemic of pandemic strain influenza is imported into an at-risk country is largely determined by the course of the epidemic in the source region and the number of travelers attempting to enter the at-risk country, and is little affected by non-pharmaceutical interventions targeting these travelers. Short of preventing international travel altogether, eradicating a nascent pandemic in the source region appears to be the only reliable method of preventing country-to-country spread of a pandemic strain of influenza

Evolutionary Dynamics Analysis of Human Metapneumovirus Subtype A2: Genetic Evidence for Its Dominant Epidemic

Human metapneumovirus (hMPV) is a respiratory viral pathogen in children worldwide. hMPV is divided into four subtypes: hMPV_A1, hMPV_A2, hMPV_B1, and hMPV_B2. hMPV_A2 can be further divided into hMPV_A2a and A2b based on phylogenetic analysis. The typical prevalence pattern of hMPV involves a shift of the predominant subtype within one or two years. However, hMPV_A2, in particular hMPV_A2b, has circulated worldwide with a several years long term high epidemic. To study this distinct epidemic behavior of hMPV_A2, we analyzed 294 sequences of partial G genes of the virus from different countries. Molecular evolutionary data indicates that hMPV_A2 evolved toward heterogeneity faster than the other subtypes. Specifically, a Bayesian skyline plot analysis revealed that hMPV_A2 has undergone a generally upward fluctuation since 1997, whereas the other subtypes experienced only one upward fluctuation. Although hMPV_A2 showed a lower value of mean dN/dS than the other subtypes, it had the largest number of positive selection sites. Meanwhile, various styles of mutation were observed in the mutation hotspots of hMPV_A2b. Bayesian phylogeography analysis also revealed two fusions of diffusion routes of hMPV_A2b in India (June 2006) and Beijing, China (June 2008). Sequences of hMPV_A2b retrieved from GenBank boosted simultaneously with the two fusions respectively, indicating that fusion of genetic transmission routes from different regions improved survival of hMPV_A2. Epidemic and evolutionary dynamics of hMPV_A2b were similar to those of hMPV_A2. Overall, our findings provide important molecular insights into hMPV epidemics and viral variation, and explain the occurrence of an atypical epidemic of hMPV_A2, particularly hMPV_A2b

Peptide Inhibitors of Dengue-Virus Entry Target a Late-Stage Fusion Intermediate

The mechanism of membrane fusion by “class II” viral fusion proteins follows a pathway that involves large-scale domain rearrangements of the envelope glycoprotein (E) and a transition from dimers to trimers. The rearrangement is believed to proceed by an outward rotation of the E ectodomain after loss of the dimer interface, followed by a reassociation into extended trimers. The ∼55-aa-residue, membrane proximal “stem” can then zip up along domain II, bringing together the transmembrane segments of the C-terminus and the fusion loops at the tip of domain II. We find that peptides derived from the stem of dengue-virus E bind stem-less E trimer, which models a conformational intermediate. In vitro assays demonstrate that these peptides specifically block viral fusion. The peptides inhibit infectivity with potency proportional to their affinity for the conformational intermediate, even when free peptide is removed from a preincubated inoculum before infecting cells. We conclude that peptides bind virions before attachment and are carried with virions into endosomes, the compartment in which acidification initiates fusion. Binding depends on particle dynamics, as there is no inhibition of infectivity if preincubation and separation are at 4°C rather than 37°C. We propose a two-step model for the mechanism of fusion inhibition. Targeting a viral entry pathway can be an effective way to block infection. Our data, which support and extend proposed mechanisms for how the E conformational change promotes membrane fusion, suggest strategies for inhibiting flavivirus entry

The distinct category of healthcare associated bloodstream infections

<p>Abstract</p> <p>Background</p> <p>Bloodstream infections (BSI) have been traditionally classified as either community acquired (CA) or hospital acquired (HA) in origin. However, a third category of healthcare-associated (HCA) community onset disease has been increasingly recognized. The objective of this study was to compare and contrast characteristics of HCA-BSI with CA-BSI and HA-BSI.</p> <p>Methods</p> <p>All first episodes of BSI occurring among adults admitted to hospitals in a large health region in Canada during 2000-2007 were identified from regional databases. Cases were classified using a series of validated algorithms into one of HA-BSI, HCA-BSI, or CA-BSI and compared on a number of epidemiologic, microbiologic, and outcome characteristics.</p> <p>Results</p> <p>A total of 7,712 patients were included; 2,132 (28%) had HA-BSI, 2,492 (32%) HCA-BSI, and 3,088 (40%) had CA-BSI. Patients with CA-BSI were significantly younger and less likely to have co-morbid medical illnesses than patients with HCA-BSI or HA-BSI (p < 0.001). The proportion of cases in males was higher for HA-BSI (60%; p < 0.001 vs. others) as compared to HCA-BSI or CA-BSI (52% and 54%; p = 0.13). The proportion of cases that had a poly-microbial etiology was significantly lower for CA-BSI (5.5%; p < 0.001) compared to both HA and HCA (8.6 vs. 8.3%). The median length of stay following BSI diagnosis 15 days for HA, 9 days for HCA, and 8 days for CA (p < 0.001). Overall the most common species causing bloodstream infection were <it>Escherichia coli, Staphylococcus aureus</it>, and <it>Streptococcus pneumoniae</it>. The distribution and relative rank of importance of these species varied according to classification of acquisition. Twenty eight day all cause case-fatality rates were 26%, 19%, and 10% for HA-BSI, HCA-BSI, and CA-BSI, respectively (p < 0.001).</p> <p>Conclusion</p> <p>Healthcare-associated community onset infections are distinctly different from CA and HA infections based on a number of epidemiologic, microbiologic, and outcome characteristics. This study adds further support for the classification of community onset BSI into separate CA and HCA categories.</p