Biomass as an alternative feedstock to oleochemicals.

The huge demands for petrochemicals have led to a rapid increase in the production of these fossil-based derivatives. Biomass represents a promising feedstock for addressing the challenges related to petrochemicals in terms of the necessity to apply renewable sources and the need to decrease carbon emissions. Among the natural biomass products, most studies have attempted to upgrade natural oils owing to their promising advantages of worldwide availability, low-cost processing, and built-in functionality. This paper discusses the upgradation of natural oils to the most beneficial oleochemicals, including fatty acids, fatty alcohols, and fatty acid methyl esters. This review also covers the utility, physico-chemical properties, and the production processes for such materials. The interconnected reaction routes to produce oleochemicals and the affecting parameters (catalyst design, temperature, and pressure) are also elucidated. Furthermore, this article discusses the future perspective of oleochemicals based on their development in recent years.

Bioprosthetic mitral valve thrombosis: the role of cardiac CT in diagnosis and guiding the management.

A patient in his 60s with a bioprosthetic aortic and mitral valve replacement presented with dyspnoea, tiredness and dizziness 2 years postoperatively. Transthoracic echocardiography showed mitral valve stenosis and increased pulmonary artery pressure suggesting bioprosthetic valve failure. Cardiac CT confirmed the diagnosis of bioprosthetic mitral valve thrombosis. Treatment with anticoagulation resulted in a remarkable improvement of the valve area and gradient and complete resolution of the thrombus. Herein, we report a case of rare bioprosthetic mitral valve thrombosis.

Small molecule NOP agonists reverse locomotor sensitization induced by cocaine in male C57BL/6 mice.

Orphanin FQ/nociceptin (OFQ/N), the endogenous ligand of the nociceptin opioid receptor (NOP) has been shown to block cocaine-induced locomotor sensitization in mice and rats, and also reverses this phenomenon when injected intracerebroventricularly in animals with an established sensitized response. In the present study, we determined whether small-molecule NOP agonists would recapitulate this effect after systemic administration. Male C57BL/6 mice treated with cocaine (15 mg/kg) on days 1-3 and showed locomotor sensitization to the same dose of cocaine on day 8 were injected with vehicle or one of the two NOP agonists (AT-202 and AT-524) (but not cocaine) on days 9-11. On day 15, locomotor sensitization was assessed after a cocaine challenge (15 mg/kg). Subchronic administration of the two NOP agonists to sensitized mice significantly decreased the sensitized response on day 15. In a separate experiment conducted in male and female mice lacking NOP and their wildtype littermates, AT-524 reversed sensitization in male wildtype but not in mice lacking NOP. Further, co-administration of the NOP agonist with cocaine for three days on days 16-18 prevented the development of locomotor sensitization from this cocaine treatment in wild-type but not in NOP knockout mice. However, none of these effects of the NOP agonist was observed in female mice. Together, these results suggest that subchronic repeated administration of small-molecule NOP agonists may reverse adaptive behavioral changes associated with repeated intermittent cocaine treatment in male but not female mice.

Chronic Exposure to E-Cigarettes Elevates CYP2A5 Activity, Protein Expression, and Cotinine-Induced Production of Reactive Oxygen Species in Mice.

Coumarin 7'-hydroxylase activity, a specific marker of CYP2A5 activity, and the protein level were measured in liver microsomes of male mice after chronic exposure to e-cigarettes (e-cigs) (2.4% nicotine). After exposure for 240 minutes per day for 5 days, the activity and the protein level in preproenkephalin (ppENK)-heterozygous [ppENK (+/-)] mice were significantly elevated (P <0.05) compared with the untreated control. This elevation was not due to deletion of the ppENK gene because the activity did not differ among untreated ppENK (+/-), ppENK (-/-), and wild-type ppENK (+/+) controls. Hence, the elevation can reasonably be attributed to nicotine exposure. The production of reactive oxygen species (ROS) upon incubation of the hepatic microsomes of these mice with cotinine was higher in microsomes from the e-cig-treated mice compared with the untreated controls (P < 0.01). Liquid chromatography mass spectrometry assay showed three oxidation products of cotinine, viz trans 3'-hydroxycotinine (3'-HC), 5'-hydroxycotinine (5'-HC), and cotinine N-oxide (CNO) in the plasma of these mice. The result identifies these three oxidation reactions as the source of the observed ROS and also shows that, in nicotine-treated mice, the appropriate "nicotine metabolite ratio" is (3'-HC + 5'-HC + CNO)/cotinine. The results suggest intriguing possibilities that 1) this metabolite ratio may correlate with plasma nicotine clearance and hence impact nicotine's psychoactive effects and 2) chronic e-cig treatment causes ROS-induced oxidative stress, which may play a major role in the regulation of CYP2A5 expression. Our present results clearly show that both the activity and the protein level of CYP2A5 are elevated by repeated exposure to nicotine. SIGNIFICANCE STATEMENT: Nicotine, the psychoactive ingredient of tobacco, is eliminated as the oxidation products of cotinine in reactions catalyzed by the enzymes CYP2A5 in mice and CYP2A6 in humans. This study shows that repeated exposure to e-cigarettes elevates the level of CYP2A5 and the formation of reactive oxygen species. The results suggest an intriguing possibility that CYP2A5 may be upregulated by chronic nicotine exposure due to oxidative stress caused by the oxidation of cotinine in this preclinical model of human smokers.

Phylogenetic status and diet of red fox (Vulpes vulpes griffithii) inhabiting Ayubia National Park, Pakistan

Abstract The red fox (Vulpes vulpes) is a medium-sized carnivore that occurs in different regions of Pakistan, however, still lacks scientific data on its ecology and distribution. The current study investigated the phylogenetic status and diet of the red fox (V.v. griffithii) occurring in Ayubia National Park, Pakistan. Through camera trapping and molecular analysis, we confirmed the occurrence of red fox in the study area. Based on mitochondrial cytochrome B (304 bp) and limited sampling, nearly all red foxes of Ayubia National Park and surrounding Himalayan ranges fall within Holarctic maternal lineage, whereas red foxes found in plains of Pakistan are part of the basal Palearctic maternal lineage. Using 32 scats, we found that red fox diet comprises of 80% animal-based prey species (both wild and domestic) and 19% plant matter. The wild animal prey species included Cape hare (Lepus capensis) and flying squirrel (Pteromyini sp.), which constituted 17% and 15% of diet, respectively. Red foxes infrequently consumed House mouse (Mus musculus), Himalayan Palm civet (Paguma larvata) and sheep (Ovis aries), each comprising around 6% to 9% of red fox diet. The fox species also scavenged on domestic donkey opportunistically. Based on our sampling, our study suggests that the red fox (V.v. griffithii) that occurs in Ayubia National Park and across the lesser Himalayan ranges belongs to Holarctic maternal lineage. The study also highlights consumption of plant seeds by red foxes, indicating it may play an important ecological role in seed dispersal in Ayubia National Park.

Resumo A raposa-vermelha (Vulpes vulpes) é um carnívoro de médio porte que ocorre em diferentes regiões do Paquistão, porém ainda carece de dados científicos sobre sua ecologia e distribuição. O presente estudo investigou o status filogenético e a dieta da raposa-vermelha (V.v. griffithii) que ocorre no Parque Nacional de Ayubia, Paquistão. Por meio de armadilhas fotográficas e análises moleculares, confirmamos a ocorrência de raposa-vermelha na área de estudo. Com base no citocromo B mitocondrial (304 bp) e amostragem limitada, quase todas as raposas-vermelhas do Parque Nacional de Ayubia e áreas circundantes do Himalaia se enquadram na linhagem materna holártica, enquanto as raposas-vermelhas encontradas nas planícies do Paquistão fazem parte da linhagem materna basal paleártica. Usando 32 fezes, descobrimos que a dieta da raposa-vermelha compreende 80% de espécies de presas de origem animal (selvagens e domésticas) e 19% de matéria vegetal. As espécies de presas de animais selvagens incluíram a lebre-do-cabo (Lepus capensis) e o esquilo-voador (Pteromyini sp.), que constituíram 17% e 15% da dieta, respectivamente. As raposas-vermelhas consumiam raramente ratos domésticos (Mus musculus), algas do Himalaia (Paguma larvata) e ovelhas (Ovis aries), cada um compreendendo cerca de 6% a 9% da dieta da raposa-vermelha. A espécie de raposa também se alimentava de burros domésticos de forma oportunista. Com base em nossa amostragem, nosso estudo sugere que a raposa-vermelha (V.v. griffithii) que ocorre no Parque Nacional de Ayubia e nas cordilheiras menores do Himalaia pertence à linhagem materna holártica. O estudo também destaca o consumo de sementes de plantas por raposas-vermelhas, indicando que pode desempenhar um papel ecológico importante na dispersão de sementes no Parque Nacional de Ayubia.

Unlocking regional innovation: The role of management and organizational participation in boosting original income.

This study explores the factors influencing the innovation process and examines regional innovation management in regency and city level organizations in Indonesia. Using secondary data from financial and innovation sources, the research adopts a qualitative descriptive approach. The sample is made up of 383 regencies and 95 cities in Indonesia. The POEMS framework, which assesses five elements, is used in the analysis: Person, Object, Environment, Message/Media, and Service. The findings highlight the importance of various dimensions, including leadership, vision, and mission; income levels and regional capital spending; transparent governance and accountability mechanisms; regulatory environment; and efficient service delivery. By contextualizing the findings within the existing literature, the study adds to the body of knowledge on regional innovation management. However, limitations include relying on secondary data and focusing on specific organizational levels in Indonesia. Future research should consider primary data collection and broader samples. In designing effective strategies and policies to promote regional innovation, the findings of the study provide insights for policy makers, practitioners, and researchers.

Enhancing COVID-19 Classification Accuracy with a Hybrid SVM-LR Model.

Support ector achine (SVM) is a newer machine learning algorithm for classification, while logistic regression (LR) is an older statistical classification method. Despite the numerous studies contrasting SVM and LR, new improvements such as bagging and ensemble have been applied to them since these comparisons were made. This study proposes a new hybrid model based on SVM and LR for predicting small events per variable (EPV). The performance of the hybrid, SVM, and LR models with different EPV values was evaluated using COVID-19 data from December 2019 to May 2020 provided by the WHO. The study found that the hybrid model had better classification performance than SVM and LR in terms of accuracy, mean squared error (MSE), and root mean squared error (RMSE) for different EPV values. This hybrid model is particularly important for medical authorities and practitioners working in the face of future pandemics.

Assessing the sustainability of the homestay industry for the East Coast of Malaysia using the Delphi approach.

Homestay ecotourism in Malaysia has been extensively examined in terms of its concepts, approaches, activities, and community engagement. However, a comprehensive assessment of the sustainability factors pertaining to host families remains a critical area awaiting exploration. This is paramount for ensuring the long-term viability of homestays and fostering economic benefits within rural communities. The present study seeks to establish direct subjective measurements for evaluating the interplay between local communities, tourism, and resources in safeguarding sustainable homestays. Utilizing the Delphi approach, this research conducted interviews with 51 experts who were actively involved in six homestays located on the East Coast of Peninsular Malaysia. The objective was to identify key evaluation indicators pertinent to the homestay industry. The findings underscored the pivotal roles played by community resources and tourism in the sustainability of homestays. Additionally, environmental, economic, and social factors emerged as crucial components for maintaining the industry's sustainability. This innovative assessment methodology offers a valuable instrument for enhancing the sustainability of the homestay sector, especially in the wake of the COVID-19 pandemic. By embracing this approach, homestay operators can fortify their sustainable management practices and prepare themselves for future pandemics. This study represents a significant contribution to the field of homestay ecotourism, emphasizing the imperative for continued research in this dynamic domain.

Donor/recipient origin of lung cancer after lung transplantation by DNA short tandem repeat analysis.

Background: Lung cancer is more common in posttransplant recipients than in the general population. The objective of this study was to examine the chimerism donor/recipient cell origin of graft cancer in recipients of lung transplant. Methods: A retrospective chart review was conducted at Foch Hospital for all lung transplantations from 1989 to 2020. Short tandem repeat PCR (STR-PCR) analysis, the gold standard technique for chimerism quantification, was used to determine the donor/recipient cell origin of lung cancers in transplant patients. Results: Fourteen (1.4%) of the 1,026 patients were found to have graft lung cancer after lung transplantation, and one developed two different lung tumors in the same lobe. Among the 15 lung tumors, 10 (67%) presented with adenocarcinoma, four (27%) with squamous cell carcinoma and one with small cell lung cancer. STR analysis showed that the origin of the cancer was the donor in 10 patients (71%), the recipient in three patients (21%), and was undetermined in one patient. Median time to diagnosis was 62 months. Conclusion: The prevalence of lung cancer in lung transplant recipients is very low. However, the results of our study showed heterogeneity of genetic alterations, with 21% being of recipient origin. Our results highlight the importance of donor selection and medical supervision after lung transplantation.

Genomic analysis of wolves from Pakistan clarifies boundaries among three divergent wolf lineages.

Among the three main divergent lineages of gray wolf (Canis lupus), the Holarctic lineage is the most widespread and best-studied, particularly in North America and Europe. Less is known about Tibetan (also called Himalayan) and Indian wolf lineages in southern Asia, especially in areas surrounding Pakistan where all three lineages are thought to meet. Given the endangered status of the Indian wolf in neighboring India and unclear southwestern boundary of the Tibetan wolf range, we conducted mitochondrial and genome-wide sequencing of wolves from Pakistan and Kyrgyzstan. Sequences of the mitochondrial D-loop region of 81 wolves from Pakistan indicated contact zones between Holarctic and Indian lineages across the northern and western mountains of Pakistan. Reduced-representation genome sequencing of 8 wolves indicated an east-to-west cline of Indian to Holarctic ancestry, consistent with a contact zone between these two lineages in Pakistan. The western boundary of the Tibetan lineage corresponded to the Ladakh region of India's Himalayas with a narrow zone of admixture spanning this boundary from the Karakoram Mountains of northern Pakistan into Ladakh, India. Our results highlight the conservation significance of Pakistan's wolf populations, especially the remaining populations in Sindh and Southern Punjab that represent the highly endangered Indian lineage.

Antimicrobial profile of coagulase-negative staphylococcus isolates from categories of individuals at a neonatal intensive care unit of a tertiary hospital, Ghana.

Introduction: we compared the antimicrobial resistance profile of young infants' clinical isolates (from blood samples) of Staphylococcus epidermidis and haemolyticus with those colonizing mothers, clinical staff, and students. Also, screened for resistance to the watch and reserve classified groups, antibiotics not prescribed in the Ho Teaching Hospital (HTH), Ghana. Methods: a cross-sectional study was conducted from March to June 2018 to determine the antimicrobial susceptibility of twenty-one antimicrobials for 123 isolates consisting of 54 S. epidermidis and 69 S. haemolyticus cultured from the participants. VITEK 2 was used for antimicrobial susceptibility testing. Staphylococcal species were identified using matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF). Statistical analysis was done with Grad-Pad prism. Results: for S. epidermidis, clinical staff isolates have the highest methicillin-resistant (65%), followed by young infants' (50%) and mothers' and students' twenty-five percent each. Both young infants and clinical staff's Staphylococcus haemolyticus isolates have 100% methicillin-resistant, while mothers' and students' ones have 82% and 63%, respectively. We have identified resistance to one watch (teicoplanin), two reserves (tigecycline and fosfomycin) antimicrobial groups, and mupirocin, an unclassified group. Conclusion: identifying coagulase-negative staphylococci (CoNS) resistance to watch and reserve groups of antimicrobials in a non-previously exposed hospital calls for further studies to determine molecular mechanisms of resistance to these antimicrobials.

Developing forecasting model for future pandemic applications based on COVID-19 data 2020-2022.

Improving forecasting particularly time series forecasting accuracy, efficiency and precisely become crucial for the authorities to forecast, monitor, and prevent the COVID-19 cases so that its spread can be controlled more effectively. However, the results obtained from prediction models are inaccurate, imprecise as well as inefficient due to linear and non-linear patterns exist in the data set, respectively. Therefore, to produce more accurate and efficient COVID-19 prediction value that is closer to the true COVID-19 value, a hybrid approach has been implemented. Thus, aims of this study is (1) to propose a hybrid ARIMA-SVM model to produce better forecasting results. (2) to investigate in terms of the performance of the proposed models and percentage improvement against ARIMA and SVM models. statistical measurements such as MSE, RMSE, MAE, and MAPE then conducted to verify that the proposed models are better than ARIMA and SVM models. Empirical results with three real datasets of well-known cases of COVID-19 in Malaysia show that, compared to the ARIMA and SVM models, the proposed model generates the smallest MSE, RMSE, MAE and MAPE values for the training and testing datasets, means that the predicted value from the proposed model is closer to the actual value. These results prove that the proposed model can generate estimated values more accurately and efficiently. As compared to ARIMA and SVM, our proposed models perform much better in terms of error reduction percentages for all datasets. This is demonstrated by the maximum scores of 73.12%, 74.6%, 90.38%, and 68.99% in the MAE, MAPE, MSE, and RMSE, respectively. Therefore, the proposed model can be the best and effective way to improve prediction performance with a higher level of accuracy and efficiency in predicting cases of COVID-19.

The Role of Mu Opioid Receptors in High Fat Diet-Induced Reward and Potentiation of the Rewarding Effect of Oxycodone.

Excessive high fat diet (HFD) consumption can induce food addiction, which is believed to involve the communication between the hypothalamus and mesolimbic dopaminergic neurons, originating in the ventral tegmental area (VTA) and projecting to the nucleus accumbens (NAc). These brain areas are densely populated with opioid receptors, raising the possibility that these receptors, and particularly mu opioid receptors (MORs), are involved in rewards elicited by palatable food. This study sought to investigate the involvement of MORs in HFD-induced reward and if there is any difference between male and female subjects in this response. We also assessed if exposure to HFD would alter the rewarding action of oxycodone, a relatively selective MOR agonist. The place conditioning paradigm was used as an animal model of reward to determine if short-time (STC, 2 h) or long-time (LTC, 16 h) conditioning with HFD induces reward or alters the rewarding action of oxycodone. Male and female C57BL/6J mice as well as MOR knockout and their wildtype littermates of both sexes were tested for basal place preference on day 1 and then conditioned with an HFD in one chamber and a regular chow diet (RCD) in another chamber for 2 h on alternate days. Three sets of STC were used, followed by a set of LTC. Each set of conditioning consisted of two conditioning with RCD and two conditioning with HFD. Mice were tested for place preference after each set of STC and again after LTC. Controls were conditioned with RCD in both conditioning chambers. Following the last place preference test, mice were treated with oxycodone and conditioned in the HFD-paired chamber and with saline in the RCD-paired chamber for one hour once a day to explore the possibility if the HFD could alter oxycodone reward. The result showed that HFD induced conditioned place preference (CPP) in male but not female subjects. However, oxycodone conditioning elicited reward in both male and female mice of the HFD group but not the control group, showing that prior conditioning with HFD potentiated the rewarding action of oxycodone. The latter response was mediated via MORs, as it was blunted in MOR knockout mice. Similarly, HFD-induced CPP was blunted in male MOR knockout mice, suggesting sexual dimorphism in this response.

Improvement of Time Forecasting Models Using Machine Learning for Future Pandemic Applications Based on COVID-19 Data 2020-2022.

Improving forecasts, particularly the accuracy, efficiency, and precision of time-series forecasts, is becoming critical for authorities to predict, monitor, and prevent the spread of the Coronavirus disease. However, the results obtained from the predictive models are imprecise and inefficient because the dataset contains linear and non-linear patterns, respectively. Linear models such as autoregressive integrated moving average cannot be used effectively to predict complex time series, so nonlinear approaches are better suited for such a purpose. Therefore, to achieve a more accurate and efficient predictive value of COVID-19 that is closer to the true value of COVID-19, a hybrid approach was implemented. Therefore, the objectives of this study are twofold. The first objective is to propose intelligence-based prediction methods to achieve better prediction results called autoregressive integrated moving average-least-squares support vector machine. The second objective is to investigate the performance of these proposed models by comparing them with the autoregressive integrated moving average, support vector machine, least-squares support vector machine, and autoregressive integrated moving average-support vector machine. Our investigation is based on three COVID-19 real datasets, i.e., daily new cases data, daily new death cases data, and daily new recovered cases data. Then, statistical measures such as mean square error, root mean square error, mean absolute error, and mean absolute percentage error were performed to verify that the proposed models are better than the autoregressive integrated moving average, support vector machine model, least-squares support vector machine, and autoregressive integrated moving average-support vector machine. Empirical results using three recent datasets of known the Coronavirus Disease-19 cases in Malaysia show that the proposed model generates the smallest mean square error, root mean square error, mean absolute error, and mean absolute percentage error values for training and testing datasets compared to the autoregressive integrated moving average, support vector machine, least-squares support vector machine, and autoregressive integrated moving average-support vector machine models. This means that the predicted value of the proposed model is closer to the true value. These results demonstrate that the proposed model can generate estimates more accurately and efficiently. Compared to the autoregressive integrated moving average, support vector machine, least-squares support vector machine, and autoregressive integrated moving average-support vector machine models, our proposed models perform much better in terms of percent error reduction for both training and testing all datasets. Therefore, the proposed model is possibly the most efficient and effective way to improve prediction for future pandemic performance with a higher level of accuracy and efficiency.

The Involvement of Endogenous Enkephalins in Glucose Homeostasis.

Obesity has nearly tripled since 1975 and is predicted to continue to escalate. The surge in obesity is expected to increase the risk of diabetes type 2, hypertension, coronary artery disease, and stroke. Therefore, it is essential to better understand the mechanisms that regulate energy and glucose homeostasis. The opioid system is implicated in regulating both aspects (hedonic and homeostatic) of food intake. Specifically, in the present study, we investigated the role of endogenous enkephalins in changes in food intake and glucose homeostasis. We used preproenkephalin (ppENK) knockout mice and their wildtype littermates/controls to assess changes in body weight, food intake, and plasma glucose levels when mice were fed a high-fat diet for 16 weeks. Body weight and food intake were measured every week (n = 21-23 mice per genotype), and at the end of the 16-week exposure period, mice were tested using the oral glucose tolerance test (OGTT, n = 9 mice per genotype) and insulin tolerance test (n = 5 mice per genotype). Our results revealed no difference in body weight or food intake between mice of the two genotypes. However, HFD-exposed enkephalin-deficient mice demonstrated impaired OGTT associated with reduced insulin sensitivity compared to their wildtype controls. The impaired insulin sensitivity is possibly due to the development of peripheral insulin resistance. Our results reveal a potential role of enkephalins in the regulation of glucose homeostasis and in the pathophysiology of diabetes type 2.

Historical perspective of code clone refactorings in evolving software.

Cloning in software is generally perceived as a threat to its maintenance and that is why it needs to be managed properly. Understanding clones from a historical perspective is essential for effective clone management. Analysis of code refactorings performed on clones in previous releases will help developers in taking decisions about clone refactoring in future releases. In this paper we perform a longitudinal study on the evolution of clone refactorings in various versions of five software systems. To perform a systematic study on clone refactoring evolution, we define clone evolution patterns for studying refactorings in a formal notation. Our results show that only a small proportion of code clones are refactored between the versions and most of the refactorings are inconsistent within clone classes. Moreover, clone refactorings may cause clone removal. Analysis of the source code of refactored clones reveals similar reasons of inconsistent refactorings and clone removal for five Java systems. This analysis will help in devising appropriate strategies for managing clone refactorings in software and hence provide foundation for devising better clone management tools.

Identification of 5-Hydroxycotinine in the Plasma of Nicotine-Treated Mice: Implications for Cotinine Metabolism and Disposition in Vivo.

Two oxidation products of cotinine, 5-hydroxycotinine (5-HC) and cotinine N-oxide (CNO), were identified for the first time in vivo in the plasma of C57BL/6 mice after injection of nicotine (1 mg/kg) or exposure to an e-cigarette (e-cig) containing 2.4% nicotine. Liquid chromatography-mass spectrometry was used to separate 3-hydroxycotinine (3-HC), 5-HC, and CNO and to quantify each by the sensitive direct detection of their parent ion with m/z of 193.097. In nicotine-injected mice, 5-HC was as abundant as 3-HC 15 minutes postinjection, and CNO was readily detectable. In e-cig-exposed mice with plasma nicotine levels resembling that of human smokers, plasma 5-HC and CNO, as well as 3-HC, were readily quantifiable at the end of the 4-hour exposure time. In nicotine-injected mice, the combined concentration of 3-HC plus 5-HC plus CNO, all formed from cotinine by CYP2A5, was higher (P < 0.01) in females than in males, although the male-female difference in cotinine plasma level did not reach statistical significance. The result highlights the importance of considering these three oxidation products of cotinine in examining cotinine metabolism and disposition. Coumarin 7-hydroxylase activity, a specific marker of CYP2A5, measured in the hepatic microsomes of untreated mice showed that females have higher activity (P < 0.001) than males (N = 8 per sex). The abundance of plasma 5-hydroxycotinine in nicotine-treated mice raises intriguing questions about the site of its origin (hepatic or possibly kidney CYP2A5) and the routes of its disposition because urinary excretion of 5-HC has not been detected by liquid chromatography with tandem mass spectrometry in mice and is controversial in human smokers. SIGNIFICANCE STATEMENT: Nicotine is the active ingredient of tobacco, but its elimination route through its biomarker cotinine is not fully understood. By liquid chromatography-mass spectrometry, this study has identified and quantified for the first time 5-hydroxycotinine and cotinine N-oxide, which are oxidation products of cotinine, in the plasma of mice treated with nicotine or exposed to e-cigarettes. The results raise intriguing questions about nicotine disposition in vivo in this well established preclinical model of human smokers.

Improving cardiovascular health with the patient-centered, integrated primary care HEARTS model in Trinidad and Tobago.

This article describes the introduction of the Pan American Health Organization's HEARTS in the Americas program in Trinidad and Tobago and the successful experiences and challenges encountered in introducing and scaling it up as a strategy for strengthening the health system's response to cardiovascular diseases. Evidence about implementation of the HEARTS program in the World Health Organization's Region of the Americas was reviewed to identify the progress made, barriers, success factors and lessons learned. In 2019, the Ministry of Health commenced implementation of the program in 5 (4.9%) of the 102 primary health care centers, and by the end of 2021, it had been scaled up to 46 (45.0%) centers. The HEARTS program ensures that patients' cardiovascular health is managed in a comprehensive way through providing counseling about a healthy lifestyle, using evidence-based treatment protocols, ensuring access to essential medicines and technologies, and using a risk-based team approach, a monitoring and evaluation system and also a team-based approach to care delivery. The barriers encountered during implementation included the fragmentation of the existing health care system, the paternalistic role assumed by health care professionals, the resistance of some health care workers to change and a lack of team-based approaches to providing care. Successful implementation of the program was enabled through ensuring high-level political commitment, establishing the national HEARTS Oversight Committee, ensuring stakeholder involvement throughout all phases and implementing standardized approaches to care. When implemented in the context of existing primary health care settings, the HEARTS program provides an exceptionally well integrated and comprehensive model of care that embodies the principles of universal health care while ensuring the health of both populations and individuals. Thus, it enables and promotes a strengthened primary health care system and services that are responsive and resilient.

En este artículo se describe la introducción del programa HEARTS en las Américas de la Organización Panamericana de la Salud en Trinidad y Tabago y las experiencias satisfactorias y los desafíos encontrados con su ejecución y ampliación como estrategia para fortalecer la respuesta del sistema de salud a las enfermedades cardiovasculares. Se reunieron datos sobre la ejecución del programa HEARTS en la Región de las Américas de la Organización Mundial de la Salud con el fin de determinar cuáles han sido los avances, los obstáculos, los factores de éxito y las enseñanzas extraídas. En el año 2019, el Ministerio de Salud inició la ejecución del programa en cinco (4,9%) de los 102 centros de atención primaria de salud, y para fines del 2021, se había ampliado a 46 (45,0%). El programa HEARTS garantiza el manejo integral de la salud cardiovascular de los pacientes mediante la prestación de asesoramiento sobre hábitos saludables, la aplicación de protocolos de tratamiento basados en la evidencia, la garantía de acceso a medicamentos y tecnologías esenciales, así como el uso de un enfoque de trabajo en equipo basado en el riesgo, un sistema de monitoreo y evaluación, y un enfoque basado en el equipo para abordar la prestación de la atención. Entre los obstáculos para su ejecución se encontraron la fragmentación del sistema de atención médica, el papel paternalista asumido por los profesionales de la salud, la resistencia al cambio de algunos trabajadores de salud y la falta de enfoques de trabajo en equipo para la prestación de la atención. La ejecución satisfactoria del programa fue posible gracias a un compromiso político de alto nivel, la creación de un comité nacional de supervisión de HEARTS, la participación de las partes interesadas en todas las fases del programa y la aplicación de enfoques estandarizados para la atención. En su ejecución en el contexto de los entornos de atención primaria de salud existentes, el programa HEARTS proporciona un modelo de atención excepcionalmente bien integrado y exhaustivo que encarna los principios de acceso universal a la atención de salud al tiempo que garantiza la salud individual y poblacional. De este modo, este modelo fomenta un sistema de atención primaria de salud fortalecido y unos servicios receptivos y resilientes.

Este artigo descreve a introdução do programa HEARTS nas Américas da Organização Pan-Americana da Saúde em Trinidad e Tobago e as experiências bem-sucedidas e os desafios encontrados durante a introdução e expansão do programa como estratégia para fortalecer a resposta do sistema de saúde às doenças cardiovasculares. Analisaram-se evidências sobre a implementação do programa HEARTS na Região das Américas da Organização Mundial da Saúde para identificar os avanços obtidos, os obstáculos, os fatores de sucesso e as lições aprendidas. Em 2019, o Ministério da Saúde iniciou a implementação do programa em 5 (4,9%) dos 102 centros de atenção primária à saúde; no final de 2021, o programa havia sido ampliado para 46 (45,0%) centros. O programa HEARTS assegura que a saúde cardiovascular dos pacientes seja manejada de uma forma abrangente por meio de aconselhamento sobre estilo de vida saudável, uso de protocolos de tratamento baseados em evidências, garantia de acesso a medicamentos e tecnologias essenciais e utilização de uma estratégia de equipe baseada no risco, de um sistema de monitoramento e avaliação e de uma abordagem de atendimento baseado em equipe. Os obstáculos encontrados durante a implementação incluíam a fragmentação do sistema de saúde existente, o papel paternalista assumido pelos profissionais de saúde, a resistência de alguns profissionais de saúde a mudanças e a falta de abordagens baseadas em equipe na prestação do atendimento. Para permitir que a implementação do programa fosse bem-sucedida, obteve-se compromisso político de alto nível, criou-se o Comitê de Supervisão do HEARTS nacional, assegurou-se o envolvimento de interessados diretos em todas as fases e implementaram-se abordagens padronizadas de atendimento. Quando implementado no contexto dos ambientes existentes de atenção primária à saúde, o programa HEARTS oferece um modelo de atenção excepcionalmente bem integrado e abrangente que incorpora os princípios de atenção universal à saúde, ao mesmo tempo em que garante a saúde das populações e dos indivíduos. Dessa forma, viabiliza e promove um sistema de atenção primária à saúde fortalecido e serviços responsivos e resilientes.

Composition optimization of PLA/PPC/HNT nanocomposites for mandibular fixation plate using single-factor experimental design.

The need to overcome the secondary surgery to remove implanted metal fixation plate leads to the idea of replacing the material with degradable bionanocomposite. In this research, polylactic acid/polypropylene (PLA/PPC) blends incorporated with halloysite nanotubes (HNT) (0-6 wt %) were considered as the candidate material for mandibular fixation plate. A single-factor design using Design Expert software was used to determine 20 different compositions of PLA/PPC/HNT nanocomposites and their mechanical properties were then measured. The optimization of the PLA/PPC/HNT nanocomposite composition was performed based on the nanocomposite's response to Young's modulus, tensile strength, and elongation at break. Further analysis suggested an optimum composition of 92.5/7.5 PLA/PPC with 6 wt % of HNT. The statistical results predicted that there was a 71.7% possibility that the proposed nanocomposite would have the following mechanical properties: Young's modulus of 2.18 GPa, a tensile strength of 64.16 MPa, and an elongation at break of 106.53%.

Recent advancement in polymer/halloysite nanotube nanocomposites for biomedical applications.

Halloysite nanotubes (HNTs) have recently been the subject of extensive research as a reinforcing filler. HNT is a natural nanoclay, non-toxic and biocompatible, hence, applicable in biomedical fields. This review focuses on the mechanical, thermal, and functional properties of polymer nanocomposites with HNT as a reinforcing agent from an experimental and theoretical perspective. In addition, this review also highlights the recent applications of polymer/HNT nanocomposites in the biomedical fields.