Objective: To analyze the clinical manifestations of intraocular lens (IOL) opacity after cataract surgery through case reports, and to explore its pathogenesis and diagnosis and treatment ideas, so as to provide a ba...Objective: To analyze the clinical manifestations of intraocular lens (IOL) opacity after cataract surgery through case reports, and to explore its pathogenesis and diagnosis and treatment ideas, so as to provide a basis for the early diagnosis and correct treatment of IOL opacity. Methods: The clinical data of one patient diagnosed with IOL opacity and underwent intraocular lens replacement in the Department of Ophthalmology, Affiliated Hospital of Youjiang Medical College for Nationalities in December 2023 were reported. The characteristics of IOL opacity were observed, and the research progress and pathogenesis of IOL opacity were understood by consulting the literature. Results: This patient is the first case of IOL opacity in our hospital. The specific reason is unclear. It is considered to be related to the IOL material. Conclusion: Hydrophilic acrylic IOL is widely used in clinic because of its good histocompatibility. However, due to its hydrophilicity, there are more cases of IOL opacity than other types of IOL. At present, there is no unified conclusion on the etiology and mechanism of IOL opacity. IOL opacity can seriously affect vision and is easily misdiagnosed as a posterior cataract. We should fully disperse the large pupil and carefully observe under the slit lamp. The most effective treatment for this disease is IOL replacement.展开更多
Background: Diabetes Mellitus (DM) is a growing health issue in Bangladesh, with significant complications affecting the quality of life (QoL). This study aims to assess long-term complications, treatment patterns, an...Background: Diabetes Mellitus (DM) is a growing health issue in Bangladesh, with significant complications affecting the quality of life (QoL). This study aims to assess long-term complications, treatment patterns, and QoL of diabetic patients during COVID-19. Methods: A cross-sectional study was conducted on 385 diabetic patients (aged 18-80) from tertiary hospitals in Dhaka and Mymensingh between May and October 2022. Data were collected via a semi-structured questionnaire on sociodemographics, complications, treatment patterns, and QoL (SF-12 scale). Chi-square tests, ANOVA, and linear regression were used for inferential analysis. Results: The sample predominantly included middle-aged males (41 - 55 years) with type 2 diabetes. Diabetic retinopathy (34.5%), polyneuropathy (32.2%), and hypertension (52.3%) were the most common complications. Oral medications were used by 59.7% of patients, with 29.1% on insulin. Chi-square analysis showed a significant association between treatment adherence and complications (p β = 0.45, p Conclusion: Complications in diabetic patients significantly affect QoL in Bangladesh. Treatment adherence, especially with oral medications, positively impacts QoL. There is a need for improved access to diabetes care to manage complications and enhance the overall well-being of diabetic patients.展开更多
Road traffic flow forecasting provides critical information for the operational management of road mobility challenges, and models are used to generate the forecast. This paper uses a random process to present a novel...Road traffic flow forecasting provides critical information for the operational management of road mobility challenges, and models are used to generate the forecast. This paper uses a random process to present a novel traffic modelling framework for aggregate traffic on urban roads. The main idea is that road traffic flow is random, even for the recurrent flow, such as rush hour traffic, which is predisposed to congestion. Therefore, the structure of the aggregate traffic flow model for urban roads should correlate well with the essential variables of the observed random dynamics of the traffic flow phenomena. The novelty of this paper is the developed framework, based on the Poisson process, the kinematics of urban road traffic flow, and the intermediate modelling approach, which were combined to formulate the model. Empirical data from an urban road in Ghana was used to explore the model’s fidelity. The results show that the distribution from the model correlates well with that of the empirical traffic, providing a strong validation of the new framework and instilling confidence in its potential for significantly improved forecasts and, hence, a more hopeful outlook for real-world traffic management.展开更多
Background: Since the outbreak of the COVID-19 pandemic caused massive case fatalities across the world, people have been left with significant physical and mental disabilities, which has had an adverse impact on thei...Background: Since the outbreak of the COVID-19 pandemic caused massive case fatalities across the world, people have been left with significant physical and mental disabilities, which has had an adverse impact on their quality of life. The objective of this study is to measure the short-term and long-term outcomes among COVID-19 survivors. Methods: This is a six-month-long multicentre prospective observational study, carried out in four specialized hospitals in the capital city Dhaka, where six hundred participants were enrolled by non-probability convenience sampling. Data were collected through three structured interviews, and follow-ups were done during discharge, at 1st month, and 6th month. An analytical study was done on demographic variables, socio-economic conditions, physical findings and outcomes. Data were analysed using Statistical Package for Social Sciences (SPSS). Results: A total of 600 participants were enrolled. The mean age was 49.83. Many participants belong to the age range of 31 to 40 years. More than two-thirds (72.7%) of participants were male, whereas 27.30% were female. Most patients admitted had mild and moderate COVID-19 symptoms (40% and 58%, respectively). Among short-term COVID complications, it was found that 43.3% of the participants complained of fatigue, 32.6% of depression, 24.7% of sleep disturbance, 19% of anxiety and, 5% memory loss. In long-term COVID complications the number reduced significantly: 5% of the participants complained of fatigue, 10% of depression, 2.7% of sleep disturbance, 7.3% of anxiety and, 2.7% memory loss. The severity of lung parenchymal disease also reduced in long term COVID symptoms. The study found a statistically significant relationship between age groups and CT severity index (χ2 = 9.458, p = 0.032). Most patients (29.2%) in the under-30 age group had a CT Severity Index score of 2 & 3 (29.2%). The important CT Severity Index scores for individuals aged 30 to 60 years were 3 and 4, accounting for 37.7% and 33.3%, respectively. In the over-60 age group, 40.8% of patients showed a CT Severity Index score of 4, showing a range of 51% - 75%. Conclusion: This study found that fatigue, depression, and sleep disturbances are prevalent among COVID-19 survivors;however, these symptoms generally reduce over time. Lung problems improved;however, some patients suffered from persistent effects. Older patients, especially those with pre-existing conditions, suffer from more severe outcomes. These findings underscore the need for ongoing care for COVID-19 survivors.展开更多
Background: Congenital heart disease is a public health issue due to its incidence and mortality rate. The aim of this study was to investigate the long-term mortality of children with congenital heart disease admitte...Background: Congenital heart disease is a public health issue due to its incidence and mortality rate. The aim of this study was to investigate the long-term mortality of children with congenital heart disease admitted to the Departmental University Hospital of Borgou/Alibori (CHUD-B/A) from 2011 to 2022. Methods: This descriptive longitudinal study with analytical aims covered 11 years (April 1, 2011 to December 31, 2022). It consisted of a review of the records of children under 15 years of age with echocardiographically confirmed congenital heart disease. This was followed by an interview with the parents to assess the children’s current condition. Data were entered using Kobocollect software and analyzed using R Studio 4.2.2. software. Results: A total of 143 complete files were retained. The median age at diagnosis was 14 months (IIQ: Q1 = 4;Q3 = 60) with a range of 2 days and 175 months, and the sex-ratio (M/F) was 0.96. Left-to-right shunts were the most frequent cardiopathy group (62.9%). Only 35 children (24.5%) benefited from restorative treatment. The mortality rate was 31.5%. Median survival under the maximum bias assumption was 114 months and 216 months under the assumption of minimum bias. Survival was significantly better in children with right-to-left shunts (p = 0.0049) under the assumption of minimum bias. The death risk factors were: age at diagnosis less than 12 months (aHR = 7.58;95% CI = 3.36 - 17.24;p Conclusion: The long-term mortality of congenital heart disease is high and favoured by the absence of restorative treatment. Local correction of congenital heart disease and medical follow-up will help to reduce this mortality.展开更多
Background: To prevent infectious diseases and deaths of children, vaccinations play a crucial role in public health strategies in Kuwait. However, it remained uncertain to demonstrate the potential long-term health o...Background: To prevent infectious diseases and deaths of children, vaccinations play a crucial role in public health strategies in Kuwait. However, it remained uncertain to demonstrate the potential long-term health outcomes of vaccination, including neurodevelopmental disorders (NDD) and autism. This study aimed to evaluate the long-term health outcomes of vaccination among Kuwait children from birth to thirteen years old. Objectives: This study included the significant objectives: (1) to compare long-term health effects, including chronic and acute conditions for unvaccinated, partially vaccinated, and vaccinated children, and (2) to evaluate the association of vaccination with the neurodevelopmental disorders (NDD) and autism, and the preventable illnesses. Methods: This prospective study involved a sample of 976 children from Kuwait based on mothers’ reporting. Data collection about the vaccination status of children and various health outcomes relevant to chronic and acute illnesses was performed based on structured questionnaires through an online survey. However, participants were classified into unvaccinated (n = 40), partially vaccinated (n = 222), and fully vaccinated (n = 714). Statistical analyses, including the chi-square test, Odds Ratios (OR), 95% Confidence Interval (CI), and logistic regression, were performed using SAS (Version 9.4) to determine the associations between vaccination status and health outcomes among children. Results: The study disclosed that vaccinated children showed an increased diagnosis of chronic (allergic rhinitis, allergies, autism spectrum, eczema, neuro-developmental disorders, learning disability, ADHD, and any chronic condition) and acute (whooping cough, pneumonia, rubella, hepatitis A or B, measles, mumps, meningitis, influenza, rotavirus, cancer, chronic fatigue, Crohn’s disease, inflammatory bowel disease, conduct disorder, diabetes type 1 or 2, rheumatoid arthritis, obesity, seizures, hearing loss, polio, diphtheria, tetanus, and depression) illnesses than unvaccinated children. The fully vaccinated children showed an increased prevalence of influenza diagnosis, while partially vaccinated children were more likely to be diagnosed with rheumatoid arthritis than unvaccinated children. In contrast, unvaccinated were more likely to have been diagnosed with chickenpox and encephalopathy than fully and partially vaccinated. Males with chronic and acute conditions had a lower incidence of allergies and pneumonia, respectively, whereas females had a reduced prevalence of acute illnesses, such as whooping cough, inflammatory bowel disease, and hepatitis A or B among vaccinated (n = 936;combination of partially vaccinated and fully vaccinated) children. Regarding medication use and health service applications, vaccinated children were more likely to use medications for fever, antibiotics, and allergies. In addition, they showed an increased rate of sick visits and emergency visits in the past twelve months. On the other hand, factors like age (2 - 5 years, 6 - 9 years, and 10 - 13 years), birth type (cesarian), and mother suffering during pregnancy (gestational diabetes) were significantly associated with NDD (learning disability, autism spectrum, and attention deficient hyperactivity disorder) in the adjusted analysis. In the interaction model of age and birth type, age (6 - 9 years;OR 5.3, 95% CI: 1.1, 25.3) and mother suffering (gestational diabetes;OR 2.5, 95% CI: 1.2, 5.2) during pregnancy were associated with NDD. Conclusion: The findings of this study showed that there are some cases where the infection rate is higher among the vaccinated compared to unvaccinated children, or there are no significant differences between the two groups in Kuwait. Upon controlling the factors in the interaction model, the age of 6 to 9 years and gestational diabetic mothers during pregnancy were associated with the synergistic increment of odds with NDD. These data findings are recommended to verify a larger and diverse group of samples to optimize the vaccination on health outcomes in Kuwait children.展开更多
Users face the threat of trajectory privacy leakage when using location-based service applications, especially when their behavior is collected and stored for a long period of time. This accumulated information is exp...Users face the threat of trajectory privacy leakage when using location-based service applications, especially when their behavior is collected and stored for a long period of time. This accumulated information is exploited by opponents, greatly increasing the risk of trajectory privacy leakage. This attack method is called a long-term observation attack. On the premise of ensuring lower time overhead and higher cache contribution rate, the existing methods cannot utilize cache to answer subsequent queries while also resisting long-term observation attacks. So this article proposes a trajectory privacy protection method to resist long-term observation attacks. This method combines caching technology and improves the existing differential privacy mechanism, while incorporating randomization factors that are difficult for attackers to recognize after long-term observation to enhance privacy. Search for locations in the cache of both the mobile client and edge server that can replace the user’s actual location. If there are replacement users in the cache, the query results can be obtained more quickly. Simultaneously obfuscating the spatiotemporal correlation of actual trajectories by generating confusion regions. If it does not exist, the obfuscated location generation method that resists long-term observation attacks is executed to generate the real anonymous area and send it to the service provider. The above steps can comprehensively protect the user’s trajectory privacy. The experimental results show that this method can protect user trajectories from long-term observation attacks while ensuring low time overhead and a high cache contribution rate.展开更多
Objective: The studies of long-term oxygen therapy (LTOT) for patents with connective tissue disease-related interstitial lung disease (CTD-ILD) are limited. This study aimed to evaluate the prognosis of CTD-ILD patie...Objective: The studies of long-term oxygen therapy (LTOT) for patents with connective tissue disease-related interstitial lung disease (CTD-ILD) are limited. This study aimed to evaluate the prognosis of CTD-ILD patients following the initiation of LTOT, compared to those with idiopathic pulmonary fibrosis (IPF). Methods: We conducted a retrospective analysis of patients with CTD-ILD and IPF who were introduced to LTOT between January 2014 and December 2020. Results: The study included 24 patients with CTD-ILD and 55 patients with IPF. At the initiation of LTOT, female gender, never-smoking history, higher body mass index (BMI), higher lactate dehydrogenase (LDH) level, lower pulmonary Surfactant Protein-D (SP-D) level and lower Gender-Age-Physiology (GAP) scores were more common in the CTD-ILD group (all Conclusion: Although patients with CTD-ILD had longer overall survival than those with IPF, there was no significant difference in prognosis after the initiation of LTOT between the two groups. Early intervention including treatment and management will be needed in CTD-ILD as in IPF.展开更多
On average, long-haul trucks in the U.S. use approximately 667 million gallons of fuel each year just for idling. This idling primarily facilitates climate control operations during driver rest periods. To mitigate th...On average, long-haul trucks in the U.S. use approximately 667 million gallons of fuel each year just for idling. This idling primarily facilitates climate control operations during driver rest periods. To mitigate this, our study explored ways to diminish the electrical consumption of climate control systems in class 8 trucks through innovative load reduction technologies. We utilized the CoolCalc software, developed by the National Renewable Energy Laboratory (NREL), which integrates heat transfer principles with extensive weather data from across the U.S. to mimic the environmental conditions trucks face year-round. The analysis of the CoolCalc simulations was performed using MATLAB. We assessed the impact of various technologies, including white paint, advanced curtains, and Thinsulate insulation on reducing electrical demand compared to standard conditions. Our findings indicate that trucks operating in the eastern U.S. could see electrical load reductions of up to 40%, while those in the western regions could achieve reductions as high as 55%. Such significant decreases in energy consumption mean that a 10 kWh battery system could sufficiently manage the HVAC needs of these trucks throughout the year without idling. Given that many long-haul trucks are equipped with battery systems of around 800 Ah (9.6 kWh), implementing these advanced technologies could substantially curtail the necessity for idling to power air conditioning systems.展开更多
The results of an experimental study of long-term relaxation of the photoelectret state of polycrystalline CdTe:(Ag, Cu, Cd) and Sb<sub>2</sub>Se<sub>3</sub>:Se films with an anomalous photovol...The results of an experimental study of long-term relaxation of the photoelectret state of polycrystalline CdTe:(Ag, Cu, Cd) and Sb<sub>2</sub>Se<sub>3</sub>:Se films with an anomalous photovoltaic property are presented. In such films, the residual photovoltage is caused by the separation of photocarriers by the built-in electrostatic field of the near-surface region of space charges and their asymmetric capture by deep levels of impurities or complexes, including impurity atoms and intrinsic defects, both in the bulk and on the surface of crystal grains. It has been shown that in activated films, a two-step exponential temporary relaxation of the initial photovoltage of the order of V<sub>APV</sub> ≈ (500-600) V is detected, and only 10% of it experiences long-term relaxation (t ≈ 100-120 min).展开更多
This research study represents an ongoing research effort on Unidentified Anomalous Phenomena (UAP) with a focus on anomalous propagation of radar echo returns, mirroring established theoretical constructs of gravitat...This research study represents an ongoing research effort on Unidentified Anomalous Phenomena (UAP) with a focus on anomalous propagation of radar echo returns, mirroring established theoretical constructs of gravitational effects on light, which occur at higher frequencies and shorter wavelengths within the Electromagnetic Spectrum. These influences are also illustrated through other technologies, including Light Detection and Ranging (LIDAR) and the chromatic effects captured by hyperspectral cameras. This research addresses the complexities of interpreting unusual propagation patterns, such as Long Delay Echoes (LDE) and unexpected Field Echoes (UFE), which disrupt the anticipated propagation and echo protocols, thereby challenging our understanding and comprehension of radio transmission norms that may be influenced by a form of quantum entanglement. The paper posits a significant and largely unexamined correlation between these phenomena in the context of UAP activity, highlighting the urgent need for further research and innovative strategies in navigation technology and environmental monitoring to investigate these potential occurrences, which have remained enigmatic for nearly a century. Radar signals are vulnerable to intricate dynamics that can lead to Unusual Field Echoes (UFE), resulting in emergent anomalies, such as Multiple echo returns and LDEs. This study employed a 3-centimeter marine-based X-band radar operating in two scan geometries and a portable short-range millimeter-wave Doppler radar system. An analysis of these radar echoes over a two-year study identified signal propagation that deviated from navigational standards on Plan Position Indicators (PPI). This paper explores and investigates the potential impacts of UAP on radar transmission routes. Examining these complexities makes a case for an enhanced understanding of the interactions between established technological factors and elusive aerial phenomena.展开更多
Objective: To determine the efficacy and tolerability of a long-acting intramuscular formulation of Nalmefene (Nalmefene Consta 393.1 mg) for the treatment of opioid-dependent patients. Design, Setting, and Participan...Objective: To determine the efficacy and tolerability of a long-acting intramuscular formulation of Nalmefene (Nalmefene Consta 393.1 mg) for the treatment of opioid-dependent patients. Design, Setting, and Participants: A 12 weeks, open-label, randomised controlled trial conducted between June 2009-July 2011, at 14 Hospital-based drug clinics, in the 12 countries. Participants were 18 years or older, had Diagnostic and Statistical Manual of Mental Disorders-5 opioid use disorder. Of the 3200 individuals screened, 3000 (93.7%) adults were randomized 1500 participants to receive injections of Long-acting depot formulations ofNalmefene (Nalmefene Consta 393.1 mg) given intramuscularly once in 12 weeks and 1500participants to receive extended-release Naltrexone (Vivitrol 380 mg), administered intramuscularly every fourth week for 12 weeks. Main Outcomes and Measures: The primary endpoints (protocol) were: Confirmed Opioid abstinence (percentage i.e. the number of patients who achieved complete abstinence during week 12). Confirmed abstinence or “opioid-free” was defined as a negative urine drug test for opioids and no self-reported opioid use. Weeks 1 - 4 were omitted from this endpoint to allow for stabilization of abstinence. Secondary end points included a number of days in treatment, treatment retention and craving. The study also investigated, on 275 participants, degree and time course of mu-opioid receptor occupancy following single doses of Nalmefene extended-release injection (Nalmefene Consta 393.1 mg) as well as the plasma concentration of Nalmefene and Nalmefene-3-O-glucuronide. Safety was assessed by adverse event reporting. Results: Of 3000 participants, mean (SD) age was 27.1 (±4.8) years and 831 (27.7%) were women. 1500 individuals were randomized to receive injections of Long-acting depot formulations of Nalmefene (Nalmefene Consta 393.1 mg) and 1500 to receive injections of extended-release Naltrexone (Vivitrol 380 mg);2088 participants (69.6.0%) completed the trial. Primary endpoints: Confirmed Opioid Abstinence: Complete abstinence was sustained by 86% (n = 1290) of Nalmefene patients (patients treated with Nalmefene Consta 393.1 mg, long-acting depot formulations) compared with 43% (n = 645) of patients treated with extended-release Naltrexone 380 mg (Vivitrol), during weeks 5 - 12 (χ2 = 672.34, P Secondary Endpoint: Craving: A statistically and clinically significant reduction in opioid craving was observed with Nalmefene (Nalmefene Consta 393.1 mg, long-acting depot formulations) vs. Naltrexone (extended-release Naltrexone, Vivitrol 380 mg) by week 4 (P =0.0048), which persisted every week through 12 (P < 0.0001). Patients given Nalmefene (Nalmefene Consta 393.1 mg, long-acting depot formulations) had a 75% decrease in craving from baseline to week 12. Patients given a Naltrexone (extended-release Naltrexone, Vivitrol 380 mg) had a 3% increase in craving from baseline to week 12 (Mean change in self-reporting craving). Secondary Endpoint: Treatment Retention: Long-acting intramuscular formulation of Nalmefene (Nalmefene Consta 393.1 mg) helped significantly more patients complete 12 weeks treatment (n = 1245, 83%) compared with extended-release Naltrexone (Vivitrol 380 mg) (n = 570, 38%) (χ2 = 635.53, P < 0.0001). Patients on long-acting intramuscular formulation of Nalmefene (Nalmefene Consta 393.1 mg) had longer treatment retention than patients on extended-release Naltrexone (Vivitrol 380 mg). Concentrations of Nalmefene and Nalmefene-3-O-Glucuronide in Plasma: Analyses were made of 275 study sample. There was no statistically significant difference for plasma nalmefene concentrations between days 2 and 84 (p = 0.416). The plasma concentration of Nalmefene were 20.3 and 28.5 ng/ml and concentrations of nalmefene-3-O-glucuronide were 2.1 and 4.1 ng/ml, respectively. Plasma levels of Nalmefene remained above 20 ng/ml for approximately 12 weeks after administration of Nalmefene, long-acting depot formulations (Nalmefene Consta 393.1 mg). PET Assessments: Very high mu-opioid receptor occupancy by Nalmefene was detected 1 day after treatments at which time point the occupancy was 100.0% after Nalmefene injection (Nalmefene Consta 393.1 mg). Nalmefene Consta 393.1 mg injection (long-acting intramuscular formulation of Nalmefene) led to a very high occupancy ofmu-opioid receptors in all brain areas examined;the thalamus, caudate nucleus, and frontal cortex. Depending on the brain area mu-opioid receptor occupancy varied between 83.0% and 85.8% 84 days after dosing. Adverse Reactions: Adverse events were similar in opioid-dependent patients treated with long-acting intramuscular formulation of Nalmefene (Nalmefene Consta 393.1 mg) vs. patients treated with extended-release Naltrexone (Vivitrol 380 mg). Conclusions and Relevance: Long-acting depot formulations of Nalmefene (Nalmefene Consta 393.1 mg) was more effective then extended-release Naltrexone (Vivitrol 380 mg) in maintaining short-term abstinence from heroin and should be considered as a treatment option for opioid-dependent individuals.展开更多
The negative molecular swab does not mean that the body and mind are healed: even months after Sars-CoV-2 infection, patients may continue to have symptoms. The symptoms mainly present at 6 - 12 months in patients rec...The negative molecular swab does not mean that the body and mind are healed: even months after Sars-CoV-2 infection, patients may continue to have symptoms. The symptoms mainly present at 6 - 12 months in patients recovered from COVID-19 are: asthenia, breathlessness, difficulty in breathing deeply, myalgia, psychological disorders and difficulty in concentrating such as “brain fog”. The study was conducted from June 2021 to July 2021 at Health Prevention Department in Benevento (Campania Region, South Italy). 133 patients accepted the questionnaire in the form of a telephone interview. The purpose of this study is precisely to highlight how, although a year after infection, a number of patients still show post-COVID symptoms. In particular, 77 out of 133 positive patients became Long-Haulers (58%).展开更多
Objective: To determine the efficacy and tolerability of a long-acting intramuscular formulation of Vanoxerine (Vanoxerine Consta 394.2 mg) for treatment of cocaine-dependent patients. Design, Setting, and Participant...Objective: To determine the efficacy and tolerability of a long-acting intramuscular formulation of Vanoxerine (Vanoxerine Consta 394.2 mg) for treatment of cocaine-dependent patients. Design, Setting, and Participants: A 12-week, A multicenter, randomized, placebo-controlled trial conducted between June 2009-July 2011, at 17 Hospital-based drug clinics, in the 15 countries. Participants were 18 years or older, had Diagnostic and Statistical Manual of Mental Disorders-5 cocaine use disorder. Of the 2800 patients who were assessed between March 10, 2009 to August 10, 2010, 2600 (93%) were eligible and willing to take part in the trial and were enrolled: 1300 were randomly assigned to receive injections of Long-acting depot formulations of Vanoxerine (Vanoxerine Consta 394.2 mg) given intramuscularly once in 12 weeks and 1300 to receive Placebo injections, given intramuscularly once in 12 weeks. Only 100 of 2800 patients (3.6%) did not meet the inclusion criteria. Main Outcomes and Measures: The primary endpoints (protocol) were: Confirmed Cocaine abstinence (percentage i.e. the number of patients who achieved complete abstinence during 12 weeks). Confirmed abstinence or “cocaine-free” was defined as a negative urine drug test for cocaines and no self-reported cocaine use. Secondary end points included a number of days in treatment, treatment retention and craving. The study also investigated, on 275 participants, degree and time course of Central Dopamine transporter receptor occupancy following single doses of long-acting intramuscular formulation of Vanoxerine (Vanoxerine Consta 394.2 mg) as well as the plasma concentration of Vanoxerine and 17-hydroxyl Vanoxerine. Safety was assessed by adverse event reporting. Results: Of 2600 participants, mean (SD) age was 28.5 (±5.5) years and 598 (23%) were women. 1300 individuals were randomized to receive injections of Long-acting depot formulations of Vanoxerine (Vanoxerine Consta 394.2 mg) and 1300 to receive injections of Placebo. 1417 participants (54.5.0%) completed the trial. Primary Endpoints: Confirmed Cocaine Abstinence: Complete abstinence was sustained by 72% (n = 936) of Vanoxerine patients (patients treated with Vanoxerine Consta 394.2 mg, long-acting depot formulations) compared with 37% (n = 481) of patients treated with Placebo, during weeks 5 - 12. The difference was significant as evaluated using a Chi-square test (χ2 = 672.34, P < 0.0001). Secondary Endpoint: Craving: A statistically and clinically significant reduction in cocaine craving was observed with Vanoxerine (Vanoxerine Consta 394.2 mg, long-acting depot formulations) vs. Placeboby week 4 (P = 0.0048), which persisted every week through 12 (P < 0.0001). Patients given Vanoxerine (Vanoxerine Consta 394.2 mg, long-acting depot formulations) had a 87% decrease in craving from baseline to 12th week. Patients given a Placebo had a 2% increase in craving from baseline to 12th week. Secondary Endpoint: Treatment Retention: Long-acting intramuscular formulation of Vanoxerine (Vanoxerine Consta 394.2 mg) helped significantly more patients complete 12 weeks treatment (n = 936, 72%) compared with Placebo (n = 481, 37%) (χ2 = 635.53, P < 0.0001). Patients on the long-acting intramuscular formulation of Vanoxerine (Vanoxerine Consta 394.2 mg) had longer treatment retention than patients on Placebo. Concentrations of Vanoxerine and 17-Hydroxyl Vanoxerinein Plasma: Analyses were made of 275 study samples. There was no statistically significant difference for plasma Vanoxerine concentrations between days 2 and 84 (p = 0.416). The plasma concentration of Vanoxerine were 70.4 and 94.3 ng/ml and concentrations of 17-hydroxyl Vanoxerine were 10.5 and 13.2 ng/ml, respectively. Plasma levels of Vanoxerine remained above 70 ng/ml for approximately 12 weeks after administration of Vanoxerine, long-acting depot formulations (Vanoxerine Consta 394.2 mg). PET Assessments: Very high central dopamine transporter receptor occupancy by Vanoxerine was detected 1 day after treatments, at which time point the occupancy was 100.0% after Vanoxerine injection (Vanoxerine Consta 394.2 mg). At days 7, 28, 56 and 84 post-Vanoxerine Consta 394.2 mg administration, occupancies were 95% to 79%. Vanoxerine Consta 394.2 mg injection (long-acting intramuscular formulation of Vanoxerine) led to very high occupancy of Central Dopamine transporter receptors in all brain areas examined;nucleus accumbens, caudate nucleus and putamen. Depending on the brain area Central Dopamine transporter receptor occupancy varied between 95.0% and 79% at days 7, 28, 56 and 84 after dosing. High Vanoxerine occupancy (77%) persisted at 12 weeks after the dosings. Adverse Reactions: Adverse events were similar in cocaine-dependent patients treated with the long-acting intramuscular formulation of Vanoxerine (Vanoxerine Consta 394.2 mg) vs. patients treated with Placebo. Conclusions and Relevance: Long-acting depot formulations of Vanoxerine (Vanoxerine Consta 394.2 mg) were more effective than Placebo injection in maintaining short-term abstinence from cocaine and should be considered as a treatment option for cocaine-dependent individuals.展开更多
Long-chain acyl-Co A synthetase(ACSL) family members include five different ACSL isoforms, each encoded by a separate gene and have multiple spliced variants. ACSLs on endoplasmic reticulum and mitochondrial outer mem...Long-chain acyl-Co A synthetase(ACSL) family members include five different ACSL isoforms, each encoded by a separate gene and have multiple spliced variants. ACSLs on endoplasmic reticulum and mitochondrial outer membrance catalyze fatty acids with chain lengths from 12 to 20 carbon atoms to form acyl-Co As, which are lipid metabolic intermediates and involved in fatty acid metabolism, membrane modifications and various physiological processes. Gain- or lossof-function studies have shown that the expression of individual ACSL isoforms can alter the distribution and amount of intracellular fatty acids. Changes in the types and amounts of fatty acids, in turn, can alter the expression of intracellular ACSLs. ACSL family members affect not only the proliferation of normal cells, but the proliferation of malignant tumor cells. They also regulate cell apoptosis through different signaling pathways and molecular mechanisms. ACSL members have individual functions in fatty acid metabolism in different types of cells depending on substrate preferences, subcellular location and tissue specificity, thus contributing to liver diseases and metabolic diseases, such as fatty liver disease, obesity, atherosclerosis and diabetes. They are also linked to neurological disorders and other diseases. However, the mechanisms are unclear. This review addresses new findings in the classification and properties of ACSLs and the fatty acid metabolismassociated effects of ACSLs in diseases.展开更多
Using the hourly precipitation records of meteorological stations in Shanghai, covering a period of almost a century (1916-2014), the long-term variation of extreme heavy precipitation in Shanghai on multiple spatia...Using the hourly precipitation records of meteorological stations in Shanghai, covering a period of almost a century (1916-2014), the long-term variation of extreme heavy precipitation in Shanghai on multiple spatial and temporal scales is analyzed, and the effects of urbanization on hourly rainstorms studied. Results show that: (1) Over the last century, extreme hourly precipitation events enhanced significantly. During the recent urbanization period from 1981 to 2014, the frequency of heavy precipitation increased significantly, with a distinct localized and abrupt characteristic. (2) The spatial distribution of long-term trends for the occurrence frequency and total precipitation intensity of hourly heavy precipitation in Shanghai shows a distinct urban rain-island feature; namely, heavy precipitation was increasingly focused in urban and suburban areas. Attribution analysis shows that urbanization in Shanghai contributed greatly to the increase in both frequency and intensity of heavy rainfall events in the city, thus leading to an increasing total precipitation amount of heavy rainfall events. In addition, the diurnal variation of rainfall intensity also shows distinctive urban-rural differences, especially during late afternoon and early nighttime in the city area. (3) Regional warming, with subsequent enhancement of water vapor content, convergence of moisture flux and atmospheric instability, provided favorable physical backgrounds for the formation of extreme precipitation. This accounts for the consistent increase in hourly heavy precipitation over the whole Shanghai area during recent times.展开更多
文摘Objective: To analyze the clinical manifestations of intraocular lens (IOL) opacity after cataract surgery through case reports, and to explore its pathogenesis and diagnosis and treatment ideas, so as to provide a basis for the early diagnosis and correct treatment of IOL opacity. Methods: The clinical data of one patient diagnosed with IOL opacity and underwent intraocular lens replacement in the Department of Ophthalmology, Affiliated Hospital of Youjiang Medical College for Nationalities in December 2023 were reported. The characteristics of IOL opacity were observed, and the research progress and pathogenesis of IOL opacity were understood by consulting the literature. Results: This patient is the first case of IOL opacity in our hospital. The specific reason is unclear. It is considered to be related to the IOL material. Conclusion: Hydrophilic acrylic IOL is widely used in clinic because of its good histocompatibility. However, due to its hydrophilicity, there are more cases of IOL opacity than other types of IOL. At present, there is no unified conclusion on the etiology and mechanism of IOL opacity. IOL opacity can seriously affect vision and is easily misdiagnosed as a posterior cataract. We should fully disperse the large pupil and carefully observe under the slit lamp. The most effective treatment for this disease is IOL replacement.
文摘Background: Diabetes Mellitus (DM) is a growing health issue in Bangladesh, with significant complications affecting the quality of life (QoL). This study aims to assess long-term complications, treatment patterns, and QoL of diabetic patients during COVID-19. Methods: A cross-sectional study was conducted on 385 diabetic patients (aged 18-80) from tertiary hospitals in Dhaka and Mymensingh between May and October 2022. Data were collected via a semi-structured questionnaire on sociodemographics, complications, treatment patterns, and QoL (SF-12 scale). Chi-square tests, ANOVA, and linear regression were used for inferential analysis. Results: The sample predominantly included middle-aged males (41 - 55 years) with type 2 diabetes. Diabetic retinopathy (34.5%), polyneuropathy (32.2%), and hypertension (52.3%) were the most common complications. Oral medications were used by 59.7% of patients, with 29.1% on insulin. Chi-square analysis showed a significant association between treatment adherence and complications (p β = 0.45, p Conclusion: Complications in diabetic patients significantly affect QoL in Bangladesh. Treatment adherence, especially with oral medications, positively impacts QoL. There is a need for improved access to diabetes care to manage complications and enhance the overall well-being of diabetic patients.
文摘Road traffic flow forecasting provides critical information for the operational management of road mobility challenges, and models are used to generate the forecast. This paper uses a random process to present a novel traffic modelling framework for aggregate traffic on urban roads. The main idea is that road traffic flow is random, even for the recurrent flow, such as rush hour traffic, which is predisposed to congestion. Therefore, the structure of the aggregate traffic flow model for urban roads should correlate well with the essential variables of the observed random dynamics of the traffic flow phenomena. The novelty of this paper is the developed framework, based on the Poisson process, the kinematics of urban road traffic flow, and the intermediate modelling approach, which were combined to formulate the model. Empirical data from an urban road in Ghana was used to explore the model’s fidelity. The results show that the distribution from the model correlates well with that of the empirical traffic, providing a strong validation of the new framework and instilling confidence in its potential for significantly improved forecasts and, hence, a more hopeful outlook for real-world traffic management.
文摘Background: Since the outbreak of the COVID-19 pandemic caused massive case fatalities across the world, people have been left with significant physical and mental disabilities, which has had an adverse impact on their quality of life. The objective of this study is to measure the short-term and long-term outcomes among COVID-19 survivors. Methods: This is a six-month-long multicentre prospective observational study, carried out in four specialized hospitals in the capital city Dhaka, where six hundred participants were enrolled by non-probability convenience sampling. Data were collected through three structured interviews, and follow-ups were done during discharge, at 1st month, and 6th month. An analytical study was done on demographic variables, socio-economic conditions, physical findings and outcomes. Data were analysed using Statistical Package for Social Sciences (SPSS). Results: A total of 600 participants were enrolled. The mean age was 49.83. Many participants belong to the age range of 31 to 40 years. More than two-thirds (72.7%) of participants were male, whereas 27.30% were female. Most patients admitted had mild and moderate COVID-19 symptoms (40% and 58%, respectively). Among short-term COVID complications, it was found that 43.3% of the participants complained of fatigue, 32.6% of depression, 24.7% of sleep disturbance, 19% of anxiety and, 5% memory loss. In long-term COVID complications the number reduced significantly: 5% of the participants complained of fatigue, 10% of depression, 2.7% of sleep disturbance, 7.3% of anxiety and, 2.7% memory loss. The severity of lung parenchymal disease also reduced in long term COVID symptoms. The study found a statistically significant relationship between age groups and CT severity index (χ2 = 9.458, p = 0.032). Most patients (29.2%) in the under-30 age group had a CT Severity Index score of 2 & 3 (29.2%). The important CT Severity Index scores for individuals aged 30 to 60 years were 3 and 4, accounting for 37.7% and 33.3%, respectively. In the over-60 age group, 40.8% of patients showed a CT Severity Index score of 4, showing a range of 51% - 75%. Conclusion: This study found that fatigue, depression, and sleep disturbances are prevalent among COVID-19 survivors;however, these symptoms generally reduce over time. Lung problems improved;however, some patients suffered from persistent effects. Older patients, especially those with pre-existing conditions, suffer from more severe outcomes. These findings underscore the need for ongoing care for COVID-19 survivors.
文摘Background: Congenital heart disease is a public health issue due to its incidence and mortality rate. The aim of this study was to investigate the long-term mortality of children with congenital heart disease admitted to the Departmental University Hospital of Borgou/Alibori (CHUD-B/A) from 2011 to 2022. Methods: This descriptive longitudinal study with analytical aims covered 11 years (April 1, 2011 to December 31, 2022). It consisted of a review of the records of children under 15 years of age with echocardiographically confirmed congenital heart disease. This was followed by an interview with the parents to assess the children’s current condition. Data were entered using Kobocollect software and analyzed using R Studio 4.2.2. software. Results: A total of 143 complete files were retained. The median age at diagnosis was 14 months (IIQ: Q1 = 4;Q3 = 60) with a range of 2 days and 175 months, and the sex-ratio (M/F) was 0.96. Left-to-right shunts were the most frequent cardiopathy group (62.9%). Only 35 children (24.5%) benefited from restorative treatment. The mortality rate was 31.5%. Median survival under the maximum bias assumption was 114 months and 216 months under the assumption of minimum bias. Survival was significantly better in children with right-to-left shunts (p = 0.0049) under the assumption of minimum bias. The death risk factors were: age at diagnosis less than 12 months (aHR = 7.58;95% CI = 3.36 - 17.24;p Conclusion: The long-term mortality of congenital heart disease is high and favoured by the absence of restorative treatment. Local correction of congenital heart disease and medical follow-up will help to reduce this mortality.
文摘Background: To prevent infectious diseases and deaths of children, vaccinations play a crucial role in public health strategies in Kuwait. However, it remained uncertain to demonstrate the potential long-term health outcomes of vaccination, including neurodevelopmental disorders (NDD) and autism. This study aimed to evaluate the long-term health outcomes of vaccination among Kuwait children from birth to thirteen years old. Objectives: This study included the significant objectives: (1) to compare long-term health effects, including chronic and acute conditions for unvaccinated, partially vaccinated, and vaccinated children, and (2) to evaluate the association of vaccination with the neurodevelopmental disorders (NDD) and autism, and the preventable illnesses. Methods: This prospective study involved a sample of 976 children from Kuwait based on mothers’ reporting. Data collection about the vaccination status of children and various health outcomes relevant to chronic and acute illnesses was performed based on structured questionnaires through an online survey. However, participants were classified into unvaccinated (n = 40), partially vaccinated (n = 222), and fully vaccinated (n = 714). Statistical analyses, including the chi-square test, Odds Ratios (OR), 95% Confidence Interval (CI), and logistic regression, were performed using SAS (Version 9.4) to determine the associations between vaccination status and health outcomes among children. Results: The study disclosed that vaccinated children showed an increased diagnosis of chronic (allergic rhinitis, allergies, autism spectrum, eczema, neuro-developmental disorders, learning disability, ADHD, and any chronic condition) and acute (whooping cough, pneumonia, rubella, hepatitis A or B, measles, mumps, meningitis, influenza, rotavirus, cancer, chronic fatigue, Crohn’s disease, inflammatory bowel disease, conduct disorder, diabetes type 1 or 2, rheumatoid arthritis, obesity, seizures, hearing loss, polio, diphtheria, tetanus, and depression) illnesses than unvaccinated children. The fully vaccinated children showed an increased prevalence of influenza diagnosis, while partially vaccinated children were more likely to be diagnosed with rheumatoid arthritis than unvaccinated children. In contrast, unvaccinated were more likely to have been diagnosed with chickenpox and encephalopathy than fully and partially vaccinated. Males with chronic and acute conditions had a lower incidence of allergies and pneumonia, respectively, whereas females had a reduced prevalence of acute illnesses, such as whooping cough, inflammatory bowel disease, and hepatitis A or B among vaccinated (n = 936;combination of partially vaccinated and fully vaccinated) children. Regarding medication use and health service applications, vaccinated children were more likely to use medications for fever, antibiotics, and allergies. In addition, they showed an increased rate of sick visits and emergency visits in the past twelve months. On the other hand, factors like age (2 - 5 years, 6 - 9 years, and 10 - 13 years), birth type (cesarian), and mother suffering during pregnancy (gestational diabetes) were significantly associated with NDD (learning disability, autism spectrum, and attention deficient hyperactivity disorder) in the adjusted analysis. In the interaction model of age and birth type, age (6 - 9 years;OR 5.3, 95% CI: 1.1, 25.3) and mother suffering (gestational diabetes;OR 2.5, 95% CI: 1.2, 5.2) during pregnancy were associated with NDD. Conclusion: The findings of this study showed that there are some cases where the infection rate is higher among the vaccinated compared to unvaccinated children, or there are no significant differences between the two groups in Kuwait. Upon controlling the factors in the interaction model, the age of 6 to 9 years and gestational diabetic mothers during pregnancy were associated with the synergistic increment of odds with NDD. These data findings are recommended to verify a larger and diverse group of samples to optimize the vaccination on health outcomes in Kuwait children.
文摘Users face the threat of trajectory privacy leakage when using location-based service applications, especially when their behavior is collected and stored for a long period of time. This accumulated information is exploited by opponents, greatly increasing the risk of trajectory privacy leakage. This attack method is called a long-term observation attack. On the premise of ensuring lower time overhead and higher cache contribution rate, the existing methods cannot utilize cache to answer subsequent queries while also resisting long-term observation attacks. So this article proposes a trajectory privacy protection method to resist long-term observation attacks. This method combines caching technology and improves the existing differential privacy mechanism, while incorporating randomization factors that are difficult for attackers to recognize after long-term observation to enhance privacy. Search for locations in the cache of both the mobile client and edge server that can replace the user’s actual location. If there are replacement users in the cache, the query results can be obtained more quickly. Simultaneously obfuscating the spatiotemporal correlation of actual trajectories by generating confusion regions. If it does not exist, the obfuscated location generation method that resists long-term observation attacks is executed to generate the real anonymous area and send it to the service provider. The above steps can comprehensively protect the user’s trajectory privacy. The experimental results show that this method can protect user trajectories from long-term observation attacks while ensuring low time overhead and a high cache contribution rate.
文摘Objective: The studies of long-term oxygen therapy (LTOT) for patents with connective tissue disease-related interstitial lung disease (CTD-ILD) are limited. This study aimed to evaluate the prognosis of CTD-ILD patients following the initiation of LTOT, compared to those with idiopathic pulmonary fibrosis (IPF). Methods: We conducted a retrospective analysis of patients with CTD-ILD and IPF who were introduced to LTOT between January 2014 and December 2020. Results: The study included 24 patients with CTD-ILD and 55 patients with IPF. At the initiation of LTOT, female gender, never-smoking history, higher body mass index (BMI), higher lactate dehydrogenase (LDH) level, lower pulmonary Surfactant Protein-D (SP-D) level and lower Gender-Age-Physiology (GAP) scores were more common in the CTD-ILD group (all Conclusion: Although patients with CTD-ILD had longer overall survival than those with IPF, there was no significant difference in prognosis after the initiation of LTOT between the two groups. Early intervention including treatment and management will be needed in CTD-ILD as in IPF.
文摘On average, long-haul trucks in the U.S. use approximately 667 million gallons of fuel each year just for idling. This idling primarily facilitates climate control operations during driver rest periods. To mitigate this, our study explored ways to diminish the electrical consumption of climate control systems in class 8 trucks through innovative load reduction technologies. We utilized the CoolCalc software, developed by the National Renewable Energy Laboratory (NREL), which integrates heat transfer principles with extensive weather data from across the U.S. to mimic the environmental conditions trucks face year-round. The analysis of the CoolCalc simulations was performed using MATLAB. We assessed the impact of various technologies, including white paint, advanced curtains, and Thinsulate insulation on reducing electrical demand compared to standard conditions. Our findings indicate that trucks operating in the eastern U.S. could see electrical load reductions of up to 40%, while those in the western regions could achieve reductions as high as 55%. Such significant decreases in energy consumption mean that a 10 kWh battery system could sufficiently manage the HVAC needs of these trucks throughout the year without idling. Given that many long-haul trucks are equipped with battery systems of around 800 Ah (9.6 kWh), implementing these advanced technologies could substantially curtail the necessity for idling to power air conditioning systems.
文摘The results of an experimental study of long-term relaxation of the photoelectret state of polycrystalline CdTe:(Ag, Cu, Cd) and Sb<sub>2</sub>Se<sub>3</sub>:Se films with an anomalous photovoltaic property are presented. In such films, the residual photovoltage is caused by the separation of photocarriers by the built-in electrostatic field of the near-surface region of space charges and their asymmetric capture by deep levels of impurities or complexes, including impurity atoms and intrinsic defects, both in the bulk and on the surface of crystal grains. It has been shown that in activated films, a two-step exponential temporary relaxation of the initial photovoltage of the order of V<sub>APV</sub> ≈ (500-600) V is detected, and only 10% of it experiences long-term relaxation (t ≈ 100-120 min).
文摘This research study represents an ongoing research effort on Unidentified Anomalous Phenomena (UAP) with a focus on anomalous propagation of radar echo returns, mirroring established theoretical constructs of gravitational effects on light, which occur at higher frequencies and shorter wavelengths within the Electromagnetic Spectrum. These influences are also illustrated through other technologies, including Light Detection and Ranging (LIDAR) and the chromatic effects captured by hyperspectral cameras. This research addresses the complexities of interpreting unusual propagation patterns, such as Long Delay Echoes (LDE) and unexpected Field Echoes (UFE), which disrupt the anticipated propagation and echo protocols, thereby challenging our understanding and comprehension of radio transmission norms that may be influenced by a form of quantum entanglement. The paper posits a significant and largely unexamined correlation between these phenomena in the context of UAP activity, highlighting the urgent need for further research and innovative strategies in navigation technology and environmental monitoring to investigate these potential occurrences, which have remained enigmatic for nearly a century. Radar signals are vulnerable to intricate dynamics that can lead to Unusual Field Echoes (UFE), resulting in emergent anomalies, such as Multiple echo returns and LDEs. This study employed a 3-centimeter marine-based X-band radar operating in two scan geometries and a portable short-range millimeter-wave Doppler radar system. An analysis of these radar echoes over a two-year study identified signal propagation that deviated from navigational standards on Plan Position Indicators (PPI). This paper explores and investigates the potential impacts of UAP on radar transmission routes. Examining these complexities makes a case for an enhanced understanding of the interactions between established technological factors and elusive aerial phenomena.
文摘Objective: To determine the efficacy and tolerability of a long-acting intramuscular formulation of Nalmefene (Nalmefene Consta 393.1 mg) for the treatment of opioid-dependent patients. Design, Setting, and Participants: A 12 weeks, open-label, randomised controlled trial conducted between June 2009-July 2011, at 14 Hospital-based drug clinics, in the 12 countries. Participants were 18 years or older, had Diagnostic and Statistical Manual of Mental Disorders-5 opioid use disorder. Of the 3200 individuals screened, 3000 (93.7%) adults were randomized 1500 participants to receive injections of Long-acting depot formulations ofNalmefene (Nalmefene Consta 393.1 mg) given intramuscularly once in 12 weeks and 1500participants to receive extended-release Naltrexone (Vivitrol 380 mg), administered intramuscularly every fourth week for 12 weeks. Main Outcomes and Measures: The primary endpoints (protocol) were: Confirmed Opioid abstinence (percentage i.e. the number of patients who achieved complete abstinence during week 12). Confirmed abstinence or “opioid-free” was defined as a negative urine drug test for opioids and no self-reported opioid use. Weeks 1 - 4 were omitted from this endpoint to allow for stabilization of abstinence. Secondary end points included a number of days in treatment, treatment retention and craving. The study also investigated, on 275 participants, degree and time course of mu-opioid receptor occupancy following single doses of Nalmefene extended-release injection (Nalmefene Consta 393.1 mg) as well as the plasma concentration of Nalmefene and Nalmefene-3-O-glucuronide. Safety was assessed by adverse event reporting. Results: Of 3000 participants, mean (SD) age was 27.1 (±4.8) years and 831 (27.7%) were women. 1500 individuals were randomized to receive injections of Long-acting depot formulations of Nalmefene (Nalmefene Consta 393.1 mg) and 1500 to receive injections of extended-release Naltrexone (Vivitrol 380 mg);2088 participants (69.6.0%) completed the trial. Primary endpoints: Confirmed Opioid Abstinence: Complete abstinence was sustained by 86% (n = 1290) of Nalmefene patients (patients treated with Nalmefene Consta 393.1 mg, long-acting depot formulations) compared with 43% (n = 645) of patients treated with extended-release Naltrexone 380 mg (Vivitrol), during weeks 5 - 12 (χ2 = 672.34, P Secondary Endpoint: Craving: A statistically and clinically significant reduction in opioid craving was observed with Nalmefene (Nalmefene Consta 393.1 mg, long-acting depot formulations) vs. Naltrexone (extended-release Naltrexone, Vivitrol 380 mg) by week 4 (P =0.0048), which persisted every week through 12 (P < 0.0001). Patients given Nalmefene (Nalmefene Consta 393.1 mg, long-acting depot formulations) had a 75% decrease in craving from baseline to week 12. Patients given a Naltrexone (extended-release Naltrexone, Vivitrol 380 mg) had a 3% increase in craving from baseline to week 12 (Mean change in self-reporting craving). Secondary Endpoint: Treatment Retention: Long-acting intramuscular formulation of Nalmefene (Nalmefene Consta 393.1 mg) helped significantly more patients complete 12 weeks treatment (n = 1245, 83%) compared with extended-release Naltrexone (Vivitrol 380 mg) (n = 570, 38%) (χ2 = 635.53, P < 0.0001). Patients on long-acting intramuscular formulation of Nalmefene (Nalmefene Consta 393.1 mg) had longer treatment retention than patients on extended-release Naltrexone (Vivitrol 380 mg). Concentrations of Nalmefene and Nalmefene-3-O-Glucuronide in Plasma: Analyses were made of 275 study sample. There was no statistically significant difference for plasma nalmefene concentrations between days 2 and 84 (p = 0.416). The plasma concentration of Nalmefene were 20.3 and 28.5 ng/ml and concentrations of nalmefene-3-O-glucuronide were 2.1 and 4.1 ng/ml, respectively. Plasma levels of Nalmefene remained above 20 ng/ml for approximately 12 weeks after administration of Nalmefene, long-acting depot formulations (Nalmefene Consta 393.1 mg). PET Assessments: Very high mu-opioid receptor occupancy by Nalmefene was detected 1 day after treatments at which time point the occupancy was 100.0% after Nalmefene injection (Nalmefene Consta 393.1 mg). Nalmefene Consta 393.1 mg injection (long-acting intramuscular formulation of Nalmefene) led to a very high occupancy ofmu-opioid receptors in all brain areas examined;the thalamus, caudate nucleus, and frontal cortex. Depending on the brain area mu-opioid receptor occupancy varied between 83.0% and 85.8% 84 days after dosing. Adverse Reactions: Adverse events were similar in opioid-dependent patients treated with long-acting intramuscular formulation of Nalmefene (Nalmefene Consta 393.1 mg) vs. patients treated with extended-release Naltrexone (Vivitrol 380 mg). Conclusions and Relevance: Long-acting depot formulations of Nalmefene (Nalmefene Consta 393.1 mg) was more effective then extended-release Naltrexone (Vivitrol 380 mg) in maintaining short-term abstinence from heroin and should be considered as a treatment option for opioid-dependent individuals.
文摘The negative molecular swab does not mean that the body and mind are healed: even months after Sars-CoV-2 infection, patients may continue to have symptoms. The symptoms mainly present at 6 - 12 months in patients recovered from COVID-19 are: asthenia, breathlessness, difficulty in breathing deeply, myalgia, psychological disorders and difficulty in concentrating such as “brain fog”. The study was conducted from June 2021 to July 2021 at Health Prevention Department in Benevento (Campania Region, South Italy). 133 patients accepted the questionnaire in the form of a telephone interview. The purpose of this study is precisely to highlight how, although a year after infection, a number of patients still show post-COVID symptoms. In particular, 77 out of 133 positive patients became Long-Haulers (58%).
文摘Objective: To determine the efficacy and tolerability of a long-acting intramuscular formulation of Vanoxerine (Vanoxerine Consta 394.2 mg) for treatment of cocaine-dependent patients. Design, Setting, and Participants: A 12-week, A multicenter, randomized, placebo-controlled trial conducted between June 2009-July 2011, at 17 Hospital-based drug clinics, in the 15 countries. Participants were 18 years or older, had Diagnostic and Statistical Manual of Mental Disorders-5 cocaine use disorder. Of the 2800 patients who were assessed between March 10, 2009 to August 10, 2010, 2600 (93%) were eligible and willing to take part in the trial and were enrolled: 1300 were randomly assigned to receive injections of Long-acting depot formulations of Vanoxerine (Vanoxerine Consta 394.2 mg) given intramuscularly once in 12 weeks and 1300 to receive Placebo injections, given intramuscularly once in 12 weeks. Only 100 of 2800 patients (3.6%) did not meet the inclusion criteria. Main Outcomes and Measures: The primary endpoints (protocol) were: Confirmed Cocaine abstinence (percentage i.e. the number of patients who achieved complete abstinence during 12 weeks). Confirmed abstinence or “cocaine-free” was defined as a negative urine drug test for cocaines and no self-reported cocaine use. Secondary end points included a number of days in treatment, treatment retention and craving. The study also investigated, on 275 participants, degree and time course of Central Dopamine transporter receptor occupancy following single doses of long-acting intramuscular formulation of Vanoxerine (Vanoxerine Consta 394.2 mg) as well as the plasma concentration of Vanoxerine and 17-hydroxyl Vanoxerine. Safety was assessed by adverse event reporting. Results: Of 2600 participants, mean (SD) age was 28.5 (±5.5) years and 598 (23%) were women. 1300 individuals were randomized to receive injections of Long-acting depot formulations of Vanoxerine (Vanoxerine Consta 394.2 mg) and 1300 to receive injections of Placebo. 1417 participants (54.5.0%) completed the trial. Primary Endpoints: Confirmed Cocaine Abstinence: Complete abstinence was sustained by 72% (n = 936) of Vanoxerine patients (patients treated with Vanoxerine Consta 394.2 mg, long-acting depot formulations) compared with 37% (n = 481) of patients treated with Placebo, during weeks 5 - 12. The difference was significant as evaluated using a Chi-square test (χ2 = 672.34, P < 0.0001). Secondary Endpoint: Craving: A statistically and clinically significant reduction in cocaine craving was observed with Vanoxerine (Vanoxerine Consta 394.2 mg, long-acting depot formulations) vs. Placeboby week 4 (P = 0.0048), which persisted every week through 12 (P < 0.0001). Patients given Vanoxerine (Vanoxerine Consta 394.2 mg, long-acting depot formulations) had a 87% decrease in craving from baseline to 12th week. Patients given a Placebo had a 2% increase in craving from baseline to 12th week. Secondary Endpoint: Treatment Retention: Long-acting intramuscular formulation of Vanoxerine (Vanoxerine Consta 394.2 mg) helped significantly more patients complete 12 weeks treatment (n = 936, 72%) compared with Placebo (n = 481, 37%) (χ2 = 635.53, P < 0.0001). Patients on the long-acting intramuscular formulation of Vanoxerine (Vanoxerine Consta 394.2 mg) had longer treatment retention than patients on Placebo. Concentrations of Vanoxerine and 17-Hydroxyl Vanoxerinein Plasma: Analyses were made of 275 study samples. There was no statistically significant difference for plasma Vanoxerine concentrations between days 2 and 84 (p = 0.416). The plasma concentration of Vanoxerine were 70.4 and 94.3 ng/ml and concentrations of 17-hydroxyl Vanoxerine were 10.5 and 13.2 ng/ml, respectively. Plasma levels of Vanoxerine remained above 70 ng/ml for approximately 12 weeks after administration of Vanoxerine, long-acting depot formulations (Vanoxerine Consta 394.2 mg). PET Assessments: Very high central dopamine transporter receptor occupancy by Vanoxerine was detected 1 day after treatments, at which time point the occupancy was 100.0% after Vanoxerine injection (Vanoxerine Consta 394.2 mg). At days 7, 28, 56 and 84 post-Vanoxerine Consta 394.2 mg administration, occupancies were 95% to 79%. Vanoxerine Consta 394.2 mg injection (long-acting intramuscular formulation of Vanoxerine) led to very high occupancy of Central Dopamine transporter receptors in all brain areas examined;nucleus accumbens, caudate nucleus and putamen. Depending on the brain area Central Dopamine transporter receptor occupancy varied between 95.0% and 79% at days 7, 28, 56 and 84 after dosing. High Vanoxerine occupancy (77%) persisted at 12 weeks after the dosings. Adverse Reactions: Adverse events were similar in cocaine-dependent patients treated with the long-acting intramuscular formulation of Vanoxerine (Vanoxerine Consta 394.2 mg) vs. patients treated with Placebo. Conclusions and Relevance: Long-acting depot formulations of Vanoxerine (Vanoxerine Consta 394.2 mg) were more effective than Placebo injection in maintaining short-term abstinence from cocaine and should be considered as a treatment option for cocaine-dependent individuals.
基金Supported by National Natural Science Foundation of China,No.81373465
文摘Long-chain acyl-Co A synthetase(ACSL) family members include five different ACSL isoforms, each encoded by a separate gene and have multiple spliced variants. ACSLs on endoplasmic reticulum and mitochondrial outer membrance catalyze fatty acids with chain lengths from 12 to 20 carbon atoms to form acyl-Co As, which are lipid metabolic intermediates and involved in fatty acid metabolism, membrane modifications and various physiological processes. Gain- or lossof-function studies have shown that the expression of individual ACSL isoforms can alter the distribution and amount of intracellular fatty acids. Changes in the types and amounts of fatty acids, in turn, can alter the expression of intracellular ACSLs. ACSL family members affect not only the proliferation of normal cells, but the proliferation of malignant tumor cells. They also regulate cell apoptosis through different signaling pathways and molecular mechanisms. ACSL members have individual functions in fatty acid metabolism in different types of cells depending on substrate preferences, subcellular location and tissue specificity, thus contributing to liver diseases and metabolic diseases, such as fatty liver disease, obesity, atherosclerosis and diabetes. They are also linked to neurological disorders and other diseases. However, the mechanisms are unclear. This review addresses new findings in the classification and properties of ACSLs and the fatty acid metabolismassociated effects of ACSLs in diseases.
基金jointly supported by the Major Consulting Projects of the Chinese Academy of Engineering(“Study on Strategies and Measures for the Prevention and Control of Urban Flood and Waterlogging Disasters in China”)the Public Welfare Industry(Meteorological)Research Projects(Grant Nos.GYHY201306065,GYHY201406001)a research project of the Shanghai Meteorological Bureau(Grant No.YJ201604)
文摘Using the hourly precipitation records of meteorological stations in Shanghai, covering a period of almost a century (1916-2014), the long-term variation of extreme heavy precipitation in Shanghai on multiple spatial and temporal scales is analyzed, and the effects of urbanization on hourly rainstorms studied. Results show that: (1) Over the last century, extreme hourly precipitation events enhanced significantly. During the recent urbanization period from 1981 to 2014, the frequency of heavy precipitation increased significantly, with a distinct localized and abrupt characteristic. (2) The spatial distribution of long-term trends for the occurrence frequency and total precipitation intensity of hourly heavy precipitation in Shanghai shows a distinct urban rain-island feature; namely, heavy precipitation was increasingly focused in urban and suburban areas. Attribution analysis shows that urbanization in Shanghai contributed greatly to the increase in both frequency and intensity of heavy rainfall events in the city, thus leading to an increasing total precipitation amount of heavy rainfall events. In addition, the diurnal variation of rainfall intensity also shows distinctive urban-rural differences, especially during late afternoon and early nighttime in the city area. (3) Regional warming, with subsequent enhancement of water vapor content, convergence of moisture flux and atmospheric instability, provided favorable physical backgrounds for the formation of extreme precipitation. This accounts for the consistent increase in hourly heavy precipitation over the whole Shanghai area during recent times.