Epidemiological Trends of Dengue in One of the Western Hilly Areas of Himachal Pradesh.

Background: Dengue is one of the neglected tropical diseases, with a wide spectrum of diseases, ranging from acute febrile illness dengue fever to life-threatening dengue hemorrhagic fever or dengue shock syndrome. In recent years, it has become a major public health concern in many nonendemic areas as well. Materials and Methods: A secondary data analysis of records available with district Integrated Disease Surveillance Programme cell was conducted to study distribution (time, place, and person) of dengue from 2017 to 2022 in Kangra, a sub-Himalayan district of Himachal Pradesh (HP). Results: In the evaluated period (2017-2022), a total of 6008 cases suspected of dengue were tested and test positivity of 7% (441) with male gender predominance was found. Mean age of the diagnosed cases was 37.7 ± 16.8 years. A seasonal trend was observed starting from late August to November in all study years. Conclusion: Dengue is still a neglected disease, but it has shown its presence especially in this part of HP, indicating the need for better preparation and sensitization of vector-borne disease control program activities, especially in post-monsoon, to prevent future epidemics.

Forecasting the Problem of Excessive Oil Entrainment in a Desalter Using Spinning Drop Method.

Frequent desalter upsets in the refineries processing opportunity crude oils are often triggered by a rapid and uncontrollable buildup of the rag layer, a thick water-in-oil emulsion, at the oil-brine interface. This is caused by spontaneous emulsification of brine in oil. This study investigates a unique observation from a spinning drop (SD) tensiometer, revealing the low apparent interfacial tension and rigidity of SD caused by spontaneous emulsification. Fine droplets of brine generated through spontaneous emulsification decorate the SD surface and form a stable, low-energy bilayer. Simulated rag layers using the brines from upset incidences exhibit similar behavior, indicating that spontaneous emulsification is driven by chemical species in brine, which promote osmotic water transport. The rate of rag layer buildup correlates with the rate of spontaneous emulsification, with the temperature coefficient of interfacial tension reduction serving as a sensitive indicator. An imminent upset in the operation can be forecasted by measuring this temperature coefficient, enabling preventive measures.

Use of tranexamic acid-soaked NasoPore® in the emergency department, to reduce epistaxis admissions.

OBJECTIVES: The aim of this study was to assess the efficacy of a new emergency department (ED) intervention for the management of non-traumatic, anterior epistaxis in adult patients, aiming to reduce epistaxis admissions. DESIGN: A new epistaxis pathway was introduced for use by ED practitioners. This was disseminated in ED through an educational campaign by the ear, nose and throat team. A tranexamic acid (500 mg/5 mL)-soaked NasoPore® packing step was introduced for epistaxis which did not terminate following 10 min of simple first aid. The pathway was utilised for adult patients presenting with non-traumatic, anterior epistaxis. Pre- and post-implementation periods were defined, and all adults attending ED with non-traumatic, anterior epistaxis were included. Pre- and post-implementation epistaxis treatment interventions, admission rates and re-attendance rates were recorded by retrospective audit and compared. RESULTS: In the post-implementation group, epistaxis admissions were 51.7% (p < .05) lower than in the pre-implementation group, as a proportion of the total number attending ED with epistaxis during these periods. CONCLUSIONS: The significant reduction in epistaxis admissions demonstrates that this ED intervention is beneficial for patient outcomes.

Pressure injury incidence and impact on patients treated with prone positioning for COVID-19 ARDS.

OBJECTIVE: To determine the incidence of pressure injuries (PIs) and their impact on clinical outcomes in patients treated with prone positioning for COVID-19 acute respiratory distress syndrome (ARDS). METHOD: All patients with COVID-19 ARDS who were treated with prone positioning were categorised as cases and those who were not treated with prone positioning were categorised as controls. Demographics, clinical data and confounding variables affecting outcomes were recorded. Outcome variables of mortality and length of stay in intensive care units (ICUs) for both groups were recorded. Both groups' incidence of PIs were recorded and compared using statistical tests. Fisher's exact test was used for categorical variables, and Mann-Whitney U test was used for continuous variables. RESULTS: The sample included 212 patients, treated with prone position (n=104) and without prone treatment (n=108). The incidence of PIs was n=75 (35.4%). PIs were significantly higher in patients in the prone position (n=51, 49%) compared with patients who were not (n=24, 22%); p=0.001. Patients in the prone position were found to have lower APACHE-2 scores, longer stays on the ventilator, ICU and in the hospital. CONCLUSION: PIs are more prevalent in patients in the prone position and it adversely impacts clinical outcomes; it prolongs the length of stay on the ventilator, in the ICU and in the hospital.

Systematic Review of Protein Biomarkers in Adult Patients With Chronic Rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) is a heterogeneous condition characterized by differing inflammatory endotypes. The identification of suitable biomarkers could enable personalized approaches to treatment selection. OBJECTIVE: This study aimed to identify and summarize clinical studies of biomarkers in adults with CRS in order to inform future research into CRS endotypes. METHODS: We conducted systematic searches of MEDLINE and Web of Science from inception to January 30, 2022 and included all clinical studies of adult CRS patients and healthy controls measuring biomarkers using enzyme-linked immunosorbent assays or Luminex immunoassays. Outcomes included the name and tissue type of identified biomarkers and expression patterns within CRS phenotypes. Study quality was assessed using the National Institutes of Health quality assessment tool for observational cohort and cross-sectional studies. A narrative synthesis was performed. RESULTS: We identified 78 relevant studies involving up to 9394 patients, predominantly with CRS with nasal polyposis. Studies identified 80 biomarkers from nasal tissue, 25 from nasal secretions, 14 from nasal lavage fluid, 24 from serum, and one from urine. The majority of biomarkers found to distinguish CRS phenotypes were identified in nasal tissue, especially in nasal polyps. Serum biomarkers were more commonly found to differentiate CRS from controls. The most frequently measured biomarker was IL-5, followed by IL-13 and IL-4. Serum IgE, IL-17, pentraxin-3 and nasal phospho-janus kinase 2, IL-5, IL-6, IL-17A, granulocyte-colony stimulating factor, and interferon gamma were identified as correlated with disease severity. CONCLUSION: We have identified numerous potential biomarkers to differentiate a range of CRS phenotypes. Future studies should focus on the prognostic role of nasal tissue biomarkers or expand on the more limited studies of nasal secretions and nasal lavage fluid.We registered this study in PROSPERO (CRD42022302787).

Variability of Steroid Prescription for COVID-19 Associated Pneumonia in Real-Life, Non-Trial Settings.

The RECOVERY study documented lower 28-day mortality with the use of dexamethasone in hospitalized patients on invasive mechanical ventilation or oxygen with COVID-19 Pneumonia. We aimed to examine the practice patterns of steroids use, and their impact on mortality and length of stay in ICU. We retrospectively examined records of all patients with confirmed Covid 19 pneumonia admitted to the ICU of Dubai hospital from January 1st, 2020 - June 30th, 2020. We assigned patients to four groups (No steroids, low dose, medium dose, and high dose steroids). The primary clinical variable of interest was doses of steroids. Secondary outcomes were 28-day mortality and length of stay in ICU". We found variability in doses of steroid treatment. The most frequently used dose was the high dose. Patients who survived were on significantly higher doses of steroids and had significantly longer stays in ICU. The prescription of steroids in Covid-19 ARDS is variable. The dose of steroids impacts mortality rate and length of stay in ICU, although patients treated with high dose steroids seem to stay more days in ICU.

Evolution in Lithography Techniques: Microlithography to Nanolithography.

In this era, electronic devices such as mobile phones, computers, laptops, sensors, and many more have become a necessity in healthcare, for a pleasant lifestyle, and for carrying out tasks quickly and easily. Different types of temperature sensors, biosensors, photosensors, etc., have been developed to meet the necessities of people. All these devices have chips inside them fabricated using diodes, transistors, logic gates, and ICs. The patterning of the substrate which is used for the further development of these devices is done with the help of a technique known as lithography. In the present work, we have carried out a review on different types of lithographic techniques such as optical lithography, extreme ultraviolet lithography, electron beam lithography, X-ray lithography, and ion beam lithography. The evolution of these techniques with time and their application in device fabrication are discussed. The different exposure tools developed in the past decade to enhance the resolution of these devices are also discussed. Chemically amplified and non-chemically amplified resists with their bonding and thickness are discussed. Mask and maskless lithography techniques are discussed along with their merits and demerits. Device fabrication at micro and nano scale has been discussed. Advancements that can be made to improve the performance of these techniques are also suggested.

Impact of Non-viral Coinfections on Mortality of Severely Ill COVID-19 Patients in Dubai.

BACKGROUND: Coronavirus disease 2019 (COVID-19) infections may have been associated with secondary infection. Community-acquired or hospital-acquired such infections affect clinical outcomes. We performed a retrospective study to evaluate the impact of these infections on clinical outcomes. METHODS: This was a retrospective analysis of all consecutive patients with COVID-19 admitted to the intensive care unit (ICU) of Dubai hospital. RESULTS: Patients with secondary non-viral infections (SNIs) have higher mortality than patients without SNIs (57.3% vs. 43.7%, p=0.037). Patients with SNIs had more days on mechanical ventilation (MV) 19(11-27) vs. 5(2-10) p<0.001, more LOSICU 22 (15-33) vs. 7 (2-11) p<0.001, and more length of stay in hospital (LOSH) 28 (18-45) vs. 11.5 (6-19), p<0.001. Multiple logistic regression analyses showed that SNIs do not predict mortality. Linear logistic regression analysis showed patients with SNIs have increased length of stay in ICUs (LOSICUs), length of stay in hospitals (LOSHs), and prolonged needs for MV. CONCLUSION: SNIs are high in patients admitted to ICU for COVID-19 acute respiratory distress syndrome (ARDS). Although they do not impact mortality, they prolong the need for MV, LOSICU, and LOSH.

The effect of caring for critically ill patients with COVID-19 acute respiratory distress syndrome in undesignated intensive care unit wardson mortality and length of hospital stay.

INTRODUCTION: COVID-19 has caused 4 million deaths as of 24 August 2021. A significant number of patients were admitted to undesignated ICU areas before transfer to a desig-nated ICU owing to the unavailability of ICU beds. We aim to compare the mortality and length of stay of patients in these 2 areas. MATERIAL AND METHODS: We retrospectively studied all critically ill patients with COVID-19 pneumonia who were admitted to Dubai hospital between 1 January 2020 and 30 June 2020. Patients who transferred to wards other than designated ICU constitute cases, while those who were admitted directly to designated ICUs constitute controls. The demographics, clinical parameters, and treatment profile of these patients were recorded and compared. Mortality and length of stay were calculated. RESULTS: The sample includes 239 subjects (admitted to an undesignated ICU ward [n = 107] and directly admitted to a designated ICU ward [n = 132]). Patients admitted to an undesignated ICU had extra transfers between wards and had more days on MV (median [IQR] 18 (19) vs. 11 (14); P = 0.001), greater length of stay in the ICU (median [IQR]) 21.5 (19) vs. 15 (14); P = 0.001), and greater length of stay in hospital (median [IQR] 32 (28) vs. 21 (26); P = 0.001). Multiple logistic regression analysis showed that patients treated at an undesignated ICU have better survival (odds of death for patients cared for at an undesignated ICU was 0.347 with CI 0.178-0.676; P = 0.002). Multiple linear regression analysis also showed that patients treated at an undesignated ICU had longer stay - 4.2 days, CI 1.3-7.13, P = 0.004). CONCLUSIONS: Admission to an undesignated ICU impacts mortality and length of ICU and hospital stay.

Biosynthesis of silver nanospheres, kinetic profiling and their application in the optical sensing of mercury and chlorite ions in aqueous solutions.

Pollution of water linked to microbial decontamination and extensive use of sodium chlorite (NaClO2) as a disinfectant, especially in the face of the current COVID-19 situation, is a serious water pollution issue that needs to be addressed. In this context, an environmentally friendly and cost-effective method has been developed for the biomimetic synthesis of Ag nanospheres (Ag NSs) using aqueous extract of Piper nigrum for the detection of chlorite (ClO2-) and mercury (Hg2+) ions. The strong antioxidant properties of the biomolecules present in the Piper nigrum extract reduce silver ions (Ag+) to Ag0. After optimization of the formulation parameters, it was observed that 1 mL of piper nigrum extract was sufficient to reduce and stabilize 100 mL of 1.5 mM of Ag+ in 2.5 h at 30 °C. X-ray diffraction (XRD) pattern of Ag NSs revealed their crystalline nature and the characteristic Bragg's diffraction peaks confirmed their face cubic crystal (FCC) lattice. The characteristic reddish-brown color and absorption surface plasmon resonance (SPR) band at 435 nm confirmed the successful fabrication of Ag NSs. Kinetic analysis revealed a three-phase growth pattern involving nucleation, growth and stabilization. Transmission electron microscopy (TEM) and High-resolution transmission electron microscopy (HRTEM) micrograms, showed spherical NSs with narrow polydispersity with particle size ranging from 10 to 30 nm. The synthesized NSs were exposed to various metal ions and anions. The absorption intensity of Ag NSs quenched in the presence of mercury ions (Hg2+) among the cations and Chlorite ions (ClO2-) among the anions. The limit of detection (LOD) of 7.47 µM and 1.11 µM was evaluated from the calibration curve for Hg2+ and ClO2-, respectively. Based on these promising results, it is suggested that the method reported is a low-cost and one step biogenic protocol for the synthesis of Ag NSs and their employment for the detection of Hg2+ and ClO2-ions.

Effectiveness of Breastfeeding Support Packages in Low- and Middle-Income Countries for Infants under Six Months: A Systematic Review.

Small and nutritionally at-risk infants under six months, defined as those with wasting, underweight, or other forms of growth failure, are at high-risk of mortality and morbidity. The World Health Organisation 2013 guidelines on severe acute malnutrition highlight the need to effectively manage this vulnerable group, but programmatic challenges are widely reported. This review aims to inform future management strategies for small and nutritionally at-risk infants under six months in low- and middle-income countries (LMICs) by synthesising evidence on existing breastfeeding support packages for all infants under six months. We searched PubMed, CINAHL, Cochrane Library, EMBASE, and Global Health databases from inception to 18 July 2018. Intervention of interest were breastfeeding support packages. Studies reporting breastfeeding practices and/or caregivers'/healthcare staffs' knowledge/skills/practices for infants under six months from LMICs were included. Study quality was assessed using NICE quality appraisal checklist for intervention studies. A narrative data synthesis using the Synthesis Without Meta-analysis (SWiM) reporting guideline was conducted and key features of successful programmes identified. Of 15,256 studies initially identified, 41 were eligible for inclusion. They were geographically diverse, representing 22 LMICs. Interventions were mainly targeted at mother-infant pairs and only 7% (n = 3) studies included at-risk infants. Studies were rated to be of good or adequate quality. Twenty studies focused on hospital-based interventions, another 20 on community-based and one study compared both. Among all interventions, breastfeeding counselling (n = 6) and education (n = 6) support packages showed the most positive effect on breastfeeding practices followed by breastfeeding training (n = 4), promotion (n = 4) and peer support (n = 3). Breastfeeding education support (n = 3) also improved caregivers' knowledge/skills/practices. Identified breastfeeding support packages can serve as "primary prevention" interventions for all infants under six months in LMICs. For at-risk infants, these packages need to be adapted and formally tested in future studies. Future work should also examine impacts of breastfeeding support on anthropometry and morbidity outcomes. The review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO 2018 CRD42018102795).

Riverine plastic pollution from fisheries: Insights from the Ganges River system.

Abandoned, lost or otherwise discarded fishing gear represents a substantial proportion of global marine plastic pollution and can cause significant environmental and socio-economic impacts. Yet little is known about its presence in, and implications for, freshwater ecosystems or its downstream contribution to plastic pollution in the ocean. This study documents fishing gear-related debris in one of the world's largest plastic pollution contributing river catchments, the Ganges. Riverbank surveys conducted along the length of the river, from the coast in Bangladesh to the Himalaya in India, show that derelict fishing gear density increases with proximity to the sea. Fishing nets were the main gear type by volume and all samples examined for polymer type were plastic. Illegal gear types and restricted net mesh sizes were also recorded. Socio-economic surveys of fisher communities explored the behavioural drivers of plastic waste input from one of the world's largest inland fisheries and revealed short gear lifespans and high turnover rates, lack of appropriate end-of-life gear disposal methods and ineffective fisheries regulations. A biodiversity threat assessment identified the air-breathing aquatic vertebrate species most at risk of entanglement in, and impacts from, derelict fishing gear; namely species of threatened freshwater turtle and otter, and the endangered Ganges river dolphin. This research demonstrates a need for targeted and practical interventions to limit the input of fisheries-related plastic pollution to this major river system and ultimately, the global ocean. The approach used in this study could be replicated to examine the inputs, socio-economic drivers and ecological impacts of this previously uncharacterised but important source of plastic pollution in other major rivers worldwide.

Barriers to childhood vaccination as perceived by accredited social health activists and multipurpose health workers in Mewat, Haryana (India): A qualitative research.

BACKGROUND: As compared to other parts of the country, vaccination coverage and literacy rate in district Mewat, State Haryana (India) had been low, that is, 20.8-27% and 54%, respectively. National immunization program of the country was being implemented primarily through the field workers, and accredited social health activists (ASHAs) were one of the key grass root level link workers. AIMS: Hence, this study was carried out with the objective to identify barriers to childhood vaccination by field staff in field practice area of SHKM Govt Medical College Nalhar, Mewat as perceived by ASHAs and health workers. METHODS AND MATERIAL: The current study was a qualitative research which was conducted in the field practice area attached to SHKM Government Medical College Nalhar Mewat. Focus Group Discussions (FGDs) were carried out among health workers (MPHW-F/M) and ASHAs. STATISTICAL ANALYSIS USED: None. RESULTS AND CONCLUSIONS: The barriers to childhood vaccination as identified in the study are pain during vaccination and other side effects, additional expenditure on treatment of side effects, worsening of interpersonal relations of the functionaries (workers/ASHAs) with the beneficiaries, extra work burden, unawareness of the benefits of vaccination, myth/belief of potential risk of impotency in adulthood, denial by elders, lack of cash benefits, inaccessibility to vaccination services due to remote work places, people's beliefs in supernatural causes of childhood diseases, delayed BCG vaccination, etc., The barriers to childhood vaccination from the perspective of ASHAs and health workers are explored and identified which can be utilized in tailoring the efforts and strategies to improve the vaccination coverage.

Mucinous appendiceal adenocarcinomas: a diagnostic challenge.

Mucinous appendiceal neoplasms are rare and diagnosis is often difficult as patients present with non-specific symptoms often suggestive of appendicitis only and most diagnoses are made following post-surgery histology examination. Here we present a case of a mucinous appendiceal adenocarcinoma with areas of both Low-grade Appendiceal Mucinous Neoplasm and High-grade Appendiceal Mucinous Neoplasm, in a ruptured appendix at a district general hospital. Without early detection and treatment these pathologies can lead to pseudomyxoma peritonei, a syndrome of progressive mucinous ascites. This case highlights the limitations of radiological studies, benefits of diagnostic laparoscopy and provides a rationale for removing the mesoappendix with the appendix during routine appendectomies.

Solvothermal assisted phosphate functionalized graphitic carbon nitride quantum dots for optical sensing of Fe ions and its thermodynamic aspects.

A facile method has been proposed for the determination of Ferrous (Fe(II)) and Ferric (Fe(III)) ions using phosphate functionalized graphitic carbon nitride quantum dots (Ph-g-CNQDs) in an aqueous medium. The easy solvothermal procedure using oleic acid as the solvent yielded the Ph-g-CNQDs in less than 30 min. The communication among the Fe(II) and Fe(III) with Ph-g-CNQDs caused quenching of the blue Ph-g-CNQDs fluorescence signals. The Ph-g-CNQDs have been successfully characterized using X-ray diffractometry (XRD), X-ray Photoelectron spectroscopy (XPS), Transmission electron microscopy (TEM), Fourier Transform Infrared (FT-IR) spectroscopy, UV-vis absorption and photoluminescence spectrophotometry. The temperature dependent behavior of the Ph-g-CNQDs was also observed and various thermodynamic parameters have also been evaluated. The Ph-g-CNQDs displayed an excellent quantum yield of 60.54% using quinine sulfate as the standard reference. The developed method has been applied to water samples collected from different sources and good recoveries were observed which entitles this method as apt for real time monitoring.

A hybrid air quality early-warning framework: An hourly forecasting model with online sequential extreme learning machines and empirical mode decomposition algorithms.

Modelling air quality with a practical tool that produces real-time forecasts to mitigate risk to public health continues to face significant challenges considering the chaotic, non-linear and high dimensional nature of air quality predictor variables. The novelty of this research is to propose a hybrid early-warning artificial intelligence (AI) framework that can emulate hourly air quality variables (i.e., Particulate Matter 2.5, PM2.5; Particulate Matter 10, PM10 and lower atmospheric visibility, VIS), the atmospheric variables associated with increased respiratory induced mortality and recurrent health-care cost. Firstly, hourly air quality data series (January-2015 to December-2017) are demarcated into their respective intrinsic mode functions (IMFs) and a residual sub-series that reveal patterns and resolve data complexity characteristics, followed by partial autocorrelation function applied to each IMF and residual sub-series to unveil historical changes in air quality. To design the prescribed hybrid model, the data is partitioned into training (70%), validation (15%) and testing (15%) sub-sets. The online sequential-extreme learning machine (OS-ELM) algorithm integrated with improved complete ensemble empirical mode decomposition with adaptive noise (ICEEMDAN) is designed as a data pre-processing system to robustly extract predictive patterns and fine-tune the model generalization to a near-optimal global solution, which represents modelled air quality at hourly forecast horizons. The resulting early warning AI-based framework denoted as ICEEMDAN-OS-ELM model, is individually constructed by forecasting each IMF and residual sub-series, with hourly PM2.5, PM10, and VIS obtained by the aggregated sum of forecasted IMFs and residual sub-series. The results are benchmarked with many competing predictive approaches; e.g., hybrid ICEEMDAN-multiple-linear regression (MLR), ICEEMDAN-M5 model tree and standalone versions: OS-ELM, MLR, M5 model tree. Statistical metrics including the root-mean-square error (RMSE), mean absolute error (MAE), Willmott's Index (WI), Legates & McCabe's Index (ELM) and Nash-Sutcliffe coefficients (ENS) are used to evaluate the model's accuracy. Both visual and statistical results show that the proposed ICEEMDAN-OS-ELM model registers superior results, outperforming alternative comparison approaches. For instance, for PM2.5,ELM values ranged from 0.65-0.82 vs. 0.59-0.77 for ICEEMDAN-M5 tree, 0.59-0.74 for ICEEMDAN-MLR, 0.28-0.54 for OS-ELM, 0.27-0.54 for M5 tree and 0.25-0.53 for the MLR model. For remaining air quality variables (i.e., PM10 & VIS), the objective model (ICEEMDAN-OS-ELM) outperformed the comparative models. In particular, ICEEMDAN-OS-ELM registered relatively low RMSE/MAE, ranging from approximately 0.7-1.03 µg/m3(MAE), 1.01-1.47 µg/m3(RMSE) for PM2.5 whereas for PM10, these metrics registered a value of 1.29-3.84 µg/m3(MAE), 3.01-7.04 µg/m3(RMSE) and for Visibility, they were 0.01-3.72 µg/m3 (MAE (Mm-1)), 0.04-5.98 µg/m3 (RMSE (Mm-1)). Visual analysis of forecasted and observed air quality through a Taylor diagram illustrates the objective model's preciseness, confirming the versatility of early warning AI-model in generating air quality forecasts. The excellent performance ascertains the hybrid model's potential utility for air quality monitoring and subsequent public health risk mitigation.

Impact of a National Journal Club and Letter Writing Session on Improving Medical Students' Confidence with Critical Appraisal.

BACKGROUND: Critical appraisal is an important skill for clinicians of the future which medical students often have limited opportunities to develop. This study aimed to evaluate whether a national journal club session could improve medical students' confidence with critical appraisal. METHODS: 98 medical students attended a critical appraisal lecture and supervised journal article discussions. Junior doctor mentors supported students to submit discussion points as a letter-to-the-editor. An online cross-sectional survey was administered before and after the conference. RESULTS: 74 students responded, reporting increased confidence with critically appraising research articles (median score 2 vs 4, p<0.01) and increased understanding of why critical appraisal was important to their careers (median score 3 vs 5, p<0.01). DISCUSSION: This is the first study to demonstrate that a single national journal club session can significantly improve UK medical students' confidence with the critical appraisal process. These opportunities are valued by medical students.

Translational inhibition of APP by Posiphen: Efficacy, pharmacodynamics, and pharmacokinetics in the APP/PS1 mouse.

INTRODUCTION: Translational inhibition of amyloid precursor protein (APP) by Posiphen has been shown to reduce APP and its fragments in cell culture, animal models, and mildly cognitively impaired patients, making it a promising drug candidate for the treatment of Alzheimer's disease. METHODS: We used a mouse model of Alzheimer's disease (APP/presenilin-1) to examine Posiphen's efficacy, pharmacodynamics, and pharmacokinetics. RESULTS: Posiphen treatment normalized impairments in spatial working memory, contextual fear learning, and synaptic function in APP/presenilin-1 mice, without affecting their visual acuity, motor skills, or motivation and without affecting wild-type mice. Posiphen had a prolonged effect in reducing APP and all related peptides for at least 9 hours after the last dose. Its concentration was higher in the brain than in plasma, and the most abundant metabolite was N8-norPosiphen. DISCUSSION: This is the first study demonstrating the therapeutic efficacy of inhibiting the translation of APP and its fragments in an Alzheimer's disease model.