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In an era of global warming, addressing key agricultural development challenges, including reducing food insecurity and feeding a growing population, while building resilience to the adverse effects of climate change and minimising further environmental degradation induced by the agricultural sector requires a transformation of agricultural systems. Climate Smart Agriculture (CSA) is a sustainable agriculture approach that can help guide such a transformation by orienting agricultural system actions towards the realisation of a triple-objective – sustainably increasing agricultural productivity, adapting to climate change, and contributing to lower the concentration of greenhouse gases in the atmosphere. Yet, high levels of inequality in the distribution of land, a key natural resource for agricultural production, and land tenure insecurity may limit opportunities for widespread farmer adoption of CSA. Policy interventions, such as land reforms, that can broaden landless and land-poor farmers’ access to land as well as to markets, infrastructure and advisory services, and that can enhance farmers’ tenure security, may not only help improve equity and efficiency but also contribute to build an enabling environment for CSA, thereby enhancing environmental sustainability. This thesis comprises three papers investigating associations between CSA and land reform, with a particular emphasis on lower-income country settings. The first paper (Chapter 2) introduces and describes a conceptual framework, the Climate Smart Land Reform (CSLR) framework, which builds on theoretical and empirical literature on CSA and land reform and uncovers associations between the two concepts. It describes a CSLR as comprising of four pillars, land redistribution, land tenure reform, markets and infrastructure, and Rural Advisory Services (RAS). These four pillars are considered, within the framework, to have the potential to foster CSA adoption and to generate positive effects on a range of social, political, economic and environmental objectives that land reformers may entertain, including the three CSA objectives. The CSLR framework represents an innovative way to conceptualise how land reforms can contribute not only to socio-economic and political improvements, but also to environmental sustainability. The second paper (Chapter 3) explores the linkage presented in the CSLR framework between the land tenure reform pillar of the framework and the three CSA objectives by examining the land registration and certification programme undertaken at the end of the 1990s in Tigray (Ethiopia). The use of a difference-in-differences approach applied to an original panel dataset constructed from Earth Observation data reveals that the reform has led to progress on the three CSA objectives. This suggests that land tenure reforms can contribute to the achievement of rural development objectives, including objectives associated with climate change. The third paper (Chapter 4) is dedicated to the study of the South African land reform. It includes a historical summary of the causes and of the process that led to its launch, as well as a critical analysis comparing land reformers’ initial intentions with the actual implementation of the land reform. This analysis exposes key issues that have hampered the realisation of land reformers’ original intentions, including the implementation of inadequate measures for the transfer of land and for the provision of support services to land reform participants. Building on these findings, secondary data from a farm-household level survey are used to analyse empirically the association between the land redistribution and RAS pillars of the CSLR framework and CSA adoption. Results from the estimation of binary response models show that land redistribution participation was associated with a higher likelihood of adopting CSA, but only in the absence of RAS, thus providing evidence of the inadequacy of RAS in fostering CSA in the South African land reform context and confirming the need to enhance efforts for the establishment of a well-coordinated, multi-stakeholder and participatory RAS system.

Background: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer. Among TNBC subtypes, the luminal androgen receptor (LAR) subtype expresses high levels of androgen receptor (AR), tends to be less proliferative, and generally responds poorly to neoadjuvant therapy. Previous studies have shown that AR inhibition suppressed proliferation of AR+ or LAR subtype TNBC cells and tumor growth in xenograft models. Thus, AR is a promising therapeutic target for this TNBC subtype. Here, we identified kinase targets for enhancing the antitumor efficacy of the AR inhibitor enzalutamide in preclinical models and investigated the underlying molecular mechanisms. Methods: We performed a nonbiased high-throughput kinome siRNA screening (targeting 709 genes) to identify a synergistic partner for enhancing the antitumor efficacy of the AR inhibitor enzalutamide in AR+ LAR TNBC. The growth inhibitory effects of enzalutamide alone or combined with kinase inhibitors were determined using the sulforhodamine B staining assay and clonogenic assay. The effect of treatments on the expression of target proteins of interest was examined by Western blot analysis. Results: Enzalutamide was not effective as a single agent to inhibit the proliferation of AR+ TNBC cells (IC50 >15 µM in MDA-MB-453, CAL-51, CAL-148, MFM223, HCC2185, SUM149, SUM159, and SUM185 cells). Nonbiased high-throughput kinome siRNA screening identified PI3K/AKT/mTOR, cell cycle, and JNK pathways as potential canonical targets for combination with enzalutamide to enhance its antitumor efficacy in AR+ LAR TNBC. Among these pathways, inhibition of cell cycle progression using the CDK7 inhibitor UD-017 showed the most synergistic anti-proliferation effect with enzalutamide in AR+ LAR MDA-MB-453 (50.61% reduction in proliferation compared with enzalutamide alone, P < 0.001; and 48.98% reduction in proliferation compared with UD-017 alone, P < 0.001) and SUM185 (40.41% reduction in proliferation compared with enzalutamide alone, P < 0.05; and 42.76% reduction in proliferation compared with UD-017 alone, P < 0.05) TNBC cells. Furthermore, CDK7 knockdown using siRNA significantly enhanced the sensitivity of MDA-MB-453 (60.98%, P < 0.01) and SUM185 (30.99%, P < 0.01) cells to enzalutamide, and AR knockdown significantly enhanced the sensitivity of MDA-MB-453 (32.64%, P < 0.01) and SUM185 (43.62%, P < 0.01) cells to UD-017, in both cases with a sensitivity similar to that of enzalutamide plus UD-017. This result suggests that the synergy of enzalutamide and UD-017 results from specific targeting of AR and CDK7. Downstream target analysis revealed that the combination of enzalutamide and UD-017 dramatically reduced the expression of c-MYC. c-MYC knockdown using siRNA dramatically suppressed colony formation in both MDA-MB-453 and SUM185 cells at a degree similar to that of enzalutamide plus UD-017, whereas c-MYC overexpression reversed the synergistic effect of the combination treatment. This result suggests that UD-017 synergizes with enzalutamide through inhibition of c-MYC–mediated tumorigenesis. Conclusion: Our results suggest that enzalutamide synergizes with UD-017 by inhibiting c-MYC–mediated oncogenic activity. These in vitro data warrant future in vivo studies of the antitumor synergy of enzalutamide plus UD-017 in AR+ LAR TNBC models. Citation Format: Xuemei Xie, Marwa Manai, Jon A. Fuson, Troy Pearson, Dileep R. Rampa, Debu Tripathy, Jangsoon Lee, Naoto T. Ueno. Targeting CDK7 enhances the antitumor efficacy of enzalutamide in androgen receptor-positive triple-negative breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-08-01.

Women of reproductive age living with the human immunodeficiency virus (WRALHIV) have many complex problems regarding their disease and status. They have to access Voluntary counseling and testing (VCT) as one of the health services where they would receive antiretroviral treatment to optimize their health and improve their quality of life. The study aims to analyze the factors which determine the utilization of VCT for accessing antiretroviral treatment by WRALHIV in West Papua. It was an observational, cross-sectional study. The subject was women of reproductive age (WRA) aged 15-49 years old, receiving antiretroviral treatment at VCT of Hospitals in Manokwari, Sorong, and Fakfak. The total was 140 respondents. Data collection was carried out by interviews using a questionnaire. The data were analyzed statistically using the chi-square and logistic regression tests. Most respondents with high intensity in the utilization of VCT services were aged 15-35 years, graduated from senior high school - university, unemployed, and married. Demographic and predisposing variables were not significantly associated, but there were significant associations between enabling factors (distance) with p value=0.00 and reinforcing factor (social support) with p value=0.03 in the utilization of VCT services by WRALHIV in West Papua, in which the distance was more significant than social support in the utilization of VCT services. The easily accessible distance increases their visitation to VCT. In addition, social support had an impact on increasing the utilization of VCT services, and finally, these may improve WRALHIV quality of life.

The purpose of the paper is to investigate the attitude to risk related to low-probability, high-impact events. To do this, we compare the willingness to pay (WTP) to reduce mortality risks and the WTP for life insurance against earthquakes. We explore whether risk perception affects these measures, and exploit WTP to reduce risk of fatality to calculate the Value of a Statistical Life (VSL) related to seismic events. We rely on data from a survey administered to a representative sample of the Italian population. Our results highlight that the WTP to reduce mortality risk is lower than the WTP for life insurance, and that the correlations between risk perception and these two measures differ. The findings suggest that individuals’ preferences are directed toward risk management strategies in which the mortality risk is transferred to the capital market, rather than risk mitigation strategies involving the individual in sharing the costs and benefits with all of society.

Funding Acknowledgements Type of funding sources: None. Background Measurement of cardiac index (CI) is crucial in the hemodynamic assessment of critically ill patients. Pulmonary artery catheterization (PAC) remains the gold standard for CI evaluation, but it's invasive. Doppler trans-thoracic echocardiography (TTE) has been proposed as an accurate bedside non-invasive alternative to PAC for CI estimation, based on measurement of left ventricular outflow tract velocity time integral (LVOT-VTI) and diameter (LVOT-d). However, intrinsic limits of geometrical assumptions and practical limitations related to the intensive care unit (ICU) setting may lead to inaccurate CI calculation, mainly due to errors in LVOT-d. A body surface area (BSA)-based formula to predict LVOT-d has been proposed and validated. Including the predicted LVOT-d in the CI equation we obtained a new "simplified formula" for TTE CI estimation: CI=2,17*LVOT-VTI*HR/1000. Purpose This study aimed to assess the accuracy of a new TTE-based simplified formula, only requiring LVOT-VTI and HR, for TTE estimation of CI. Methods We prospectively enrolled all consecutive patients admitted to the ICU requiring PAC from January to December 2021 (n=74). We measured TTE-based CI method using both the "traditional formula" (traditional CI TTE) and the new "simplified formula" (simplified CI TTE), and compared the accuracy of both with the PAC-derived CI (CI PAC) as the reference method. Results As shown in Figure 1a, there was a moderate correlation (r = 0.70, p < 0.001) between traditional CI TTE and the CI PAC. A plot of the differences between traditional CI TTE and the CI PAC is illustrated in Figure 2a, resulting in a mean difference of -0.18 ± 0.58 L/min/m2, and 95% limits of agreement of -1.32 to +0.96 L/min/m2. The correlation between simplified CI TTE and CI PAC was strong (r = 0.81, p < 0.001) (Figure 1b) and resulted significantly greater than the traditional CI TTE and CI PAC correlation (p < 0.05). On Bland-Altman plot analysis (Figure 2b), the mean difference between simplified CI TTE and CI PAC was +0.19 ± 0.48 L/min/m2 with 95% limits of agreement of -0.74 to +1.13 L/min/m2. Conclusion In this study, we validated an easy-to-use and practical approach, leveraging on TTE LVOT-VTI and HR only, for non-invasive estimation of CI in ICU patients. In this peculiar setting, our formula was more reliable than the traditional CI TTE formula. However, despite the strong correlation with CI PAC, our formula introduces a slight but systematic overestimation of CI (+0.19 L/min/m2), as illustrated in the Bland-Altman plot. Therefore, this formula may be particularly useful in longitudinal CI assessment rather than precisely quantifying CI on a single measurement. This approach may thus be apt to quickly assess the hemodynamic response to pharmacological and mechanical supports during longitudinal assessment.

Voluntary blood donors are people who voluntarily donate their blood to other people and not to certain patients. Before blood is given to the recipient, a blood filter test or screening test is carried out. A screening test is a process of screening or separating blood that can be transfused and not infected with an infectious disease. Research has been conducted with the title Infectious Disease Screening Results and Hemoglobin (Hb) Levels in Voluntary Donors at the Indonesian Red Cross Blood Transfusion Unit, Jayapura City. This research was conducted for 1 month, from 13 May to 15 June 2019. The population used in this study were all voluntary donors who came to donate blood. The number of samples in this study was 45 samples. Methods for examining infectious diseases, in this case testing for HIV, HBsAg, and hemoglobin levels used were the ELISA method and Bj: 1.053 copper sulfate. 2 people (4.4%) were positive and 43 people (95.6%) negative, HBsAg test found 7 people (15.6%) positive and 38 people (84.4%) negative and Hemoglobin obtained results as many as 45 people (100%) normal.

26 p.-8 fig.-2 tab.-1 graph. abst.-+9 p. mat. supl.-10 fig.-2 tab., Common copathogenic factors, including oxidative stress and neuroinflammation, are found to play a vital role in the development of neurodegenerative disorders, including Alzheimer’s disease (AD) and Parkinson’s disease (PD). Nowadays, owing to the multifactorial character of the diseases, no effective therapies are available, thus underlying the need for new strategies. Overexpression of the enzyme GSK-3β and downregulation of the Nrf2/ARE pathway are responsible for a decrease in antioxidant defense effects. These pieces of evidence underline the usefulness of dual GSK-3β inhibitors/Nrf2 inducers. In this regard, to design a dual modulator, the structures of a curcumin-based analogue, as GSK-3β inhibitor, and a diethyl fumarate fragment, as Nrf2 inducer, were combined. Among the hybrids, 5 and 6 proved to effectively inhibit GSK-3β, while 4 and 5 showed a marked ability to activate Nrf2 together to increase the neuronal resistance to oxidative stress. These last pieces of evidence translated into specific neuroprotective effects of 4 and 5 against PD pathological events including neurotoxicity elicited by α-synuclein aggregates and 6-hydroxydopamine. Hybrid 5 also showed neuroprotective effects in a C. elegans model of PD where the activation of GSK-3β is intimately involved in Nrf2 regulation. In summary, 5 emerged as an interesting multitarget derivative, valuable to be exploited in a multitarget PD perspective., This work was supported by the University of Bologna (RFO funds), MCIU (grant no. SAF2016-76693-R), and ISCiii CIBERNED (CB18/05/00040) and EDS, partially funded by the CNR project NUTR-AGE (FOE-2019, DSB.AD004.271).

Research has been carried out with the title "Identification of Aspergillus sp. On Peanuts (Arachis hypogaea L) which are sold in Youtefa Market, Jayapura City”. The research was carried out at the Microbiology Laboratory of the Faculty of Mathematics and Natural Sciences, Cendrawasih University, from January 9, 2021 to April 9, 2021. The purpose of this study was to determine whether there was contamination of the fungus Aspergillus sp. on peanuts circulating in Youtefa Market, Jayapura city. This type of research is descriptive research with laboratory experiments. The population in this study were all peanuts (Arachis hypogaea L) which were sold at Youtefa Market, Jayapura city. The samples used in this study were peanuts (Arachis hypogaea L) in 5 different places each weighing 100 grams which were sold at the Youtefa market, and the samples were taken randomly. Isolation of Aspergillus sp. It was carried out by pouring cup method on PDA media, then macroscopic identification and microscopic identification were carried out. The results showed that samples of peanuts from 2 different types, namely 5 samples of dark brown peanuts were positive for contamination with the fungus Aspergillus sp. and 5 samples of brownish white peanuts were positive for Aspergillus sp. And Penicillium sp.

Children living with HIV (HIV+) experience increased risk of neurocognitive deficits, but standardized cognitive testing is limited in low-resource, high-prevalence settings. The Penn Computerized Neurocognitive Battery (PennCNB) was adapted for use in Botswana. This study evaluated the criterion validity of a locally adapted version of the PennCNB among a cohort of HIV+ individuals aged 10-17 years in Botswana. Participants completed the PennCNB and a comprehensive professional consensus assessment consisting of pencil-and-paper psychological assessments, clinical interview, and review of academic performance. Seventy-two participants were classified as cases (i.e., with cognitive impairment; N = 48) or controls (i.e., without cognitive impairment; N = 24). Sensitivity, specificity, positive predictive value, negative predictive value, and the area under receiver operating characteristic curves were calculated. Discrimination was acceptable, and prediction improved as the threshold for PennCNB impairment was less conservative. This research contributes to the validation of the PennCNB for use among children affected by HIV in Botswana.

The paper proposes a multi-body electromagnetic (EM) model for the quantitative evaluation of the influence of multiple human bodies in the surroundings of a radio link. Modeling of human-induced fading is the key element for the development of real-time Device-Free (or passive) Localization (DFL) and body occupancy tracking systems based on the processing of the Received Signal Strength (RSS) data recorded by radio-frequency devices. The proposed physical-statistical model, is able to relate the RSS measurements to the position, size, orientation, and random movements of people located in the link area. This novel EM model is thus instrumental for crowd sensing, occupancy estimation and people counting applications for indoor and outdoor scenarios. The paper presents the complete framework for the generic N-body scenario where the proposed EM model is based on the knife-edge approach that is generalized here for multiple targets. The EM-equivalent size of each target is then optimized to reproduce the body-induced alterations of the free space radio propagation. The predicted results are then compared against the full EM simulations obtained with a commercially available simulator. Finally, experiments are carried out to confirm the validity the proposed model using IEEE 802.15.4-compliant industrial radio devices., 13 pages, 6 figures

The explosion of artificial intelligence methods has paved the way for more sophisticated smart mobility solutions. In this work, we present a multi-camera video content analysis (VCA) system that exploits a single-shot multibox detector (SSD) network to detect vehicles, riders, and pedestrians and triggers alerts to drivers of public transportation vehicles approaching the surveilled area. The evaluation of the VCA system will address both detection and alert generation performance by combining visual and quantitative approaches. Starting from a SSD model trained for a single camera, we added a second one, under a different field of view (FOV) to improve the accuracy and reliability of the system. Due to real-time constraints, the complexity of the VCA system must be limited, thus calling for a simple multi-view fusion method. According to the experimental test-bed, the use of two cameras achieves a better balance between precision (68%) and recall (84%) with respect to the use of a single camera (i.e., 62% precision and 86% recall). In addition, a system evaluation in temporal terms is provided, showing that missed alerts (false negatives) and wrong alerts (false positives) are typically transitory events. Therefore, adding spatial and temporal redundancy increases the overall reliability of the VCA system.

Background Airway remodeling is an important pathological feature of chronic airway diseases, which leads to a progressive decline in lung function. The present study examined the anti-remodeling and anti- inflammatory effect of BIBF1000, a triple-tyrosine kinase inhibitor that targets VEGF, PDGF, and FGF receptor signaling in a mouse model of repeated ovalbumin (OVA) challenges. Methods Female Balb-c mice were immunized intraperitoneally on days 0 and 12 with 50 µg ovalbumin plus 1 mg of Al(OH)3 in 200 μl saline. Intranasal OVA challenges (20 µg/50 µl in PBS) were administered on days 26, 29, and 31, and were repeated twice a week for 3 months. Animals received vehicle or BIBF1000 (25 mg/kg, b.i.d.) through gavage from day 26 to the end of fourth month. On day 120, bronchoalveolar lavage (BAL) and lung tissue were collected for biochemical and immunohistological analysis. Results Compared to vehicle controls, treatment with BIBF1000 reduced the numbers of BAL eosinophils, macrophages, neutrophils, and lymphocytes by 70.0%, 57.9%, 47.5%, and 63.0%, respectively, and reduced IL-5 and IL-13 in BAL. Treatment with BIBF1000 reduced airway mucus secretion, peribronchial fibrosis, small airway, and pulmonary arterial wall thickness, compared to vehicle controls. Furthermore, treatment with BIBF1000 also reduced the expression of inflammatory mediators (TNF-α, IL-1β, IL-5, IL-13, MMP-2, MMP-9, COX-2, and iNOS) and inhibited ERK and AKT phosphorylation. Conclusions The protective effect afforded by triple-tyrosine kinase inhibition with BIBF1000 in reducing allergen-induced airway and arterial remodeling was associated with down-regulation of inflammatory mediators, as well as inhibition of ERK and AKT signaling pathways.

Background: Malaria represents the major parasitic disease in tropical regions, and the development of new potent drugs is of pivotal importance. In this study, a series of hybrid molecules were designed by linking the 7-chloroquinoline core of chloroquine to different fluorinated flavonoid-related scaffolds. Materials & methods: Compounds were prepared by exploiting the click chemistry approach, allowing the introduction of a 1,2,3-triazole, a privileged structural motif in antiparasitic dug discovery. Results: Compounds 1b and 1c were the most interesting and were endowed with the highest in vitro activity, mainly against a resistant Plasmodium falciparum strain. They also inhibited hemozoin formation, and 1c was more effective than chloroquine against stage V gametocytes. Conclusion: The homoisoflavone core is a new, promising antimalarial scaffold that deserves further investigation.

Latar Belakang: Pembelajaran daring merupakan pembelajaran yang dilakukan dengan sistem online dan merupakan hal baru bagi mahasiswa dan dosen sehingga membutuhkan waktu untuk beradaptasi, sehingga dapat membuat motivasi belajar mahasiswa menurun, untuk mempertahankan motivasi belajar mahasiswa, dengan cara menggunakan pembelajaran daring secara efektif. Tujuan: Tujuan penelitian ini untuk mengetahui hubungan pembelajaran daring dengan motivasi belajar mahasiswa STIK Stella Maris Makassar. Metode : Jenis penelitian ini penelitian non experimental dengan pendekatan desain cross sectional study. Populasi penelitian semua mahasiswa/i STIK Stella Maris Makassar dengan jumlah 436 orang. Pengambilan sampel menggunakan teknik non probability sampling dengan pendekatan consecutive sampling dengan jumlah 78 responden. Instrumen penelitian menggunakan kuesioner. Setelah data terkumpul, data dianalisis menggunakan uji statistik chi square. Hasil : Hasil penelitian diperoleh nilai p(0,02) < ?(0,05) yang menunjukkan bahwa ada hubungan yang bermakna antara pembelajaran daring dengan motivasi belajar mahasiswa STIK Stella Maris Makassar. Kesimpulan: Pembelajaran daring dengan menggunakan media pembelajaran seperti google classroom, zoom dan whatsapp yang dilakukan secara efektif dapat meningkatkan motivasi belajar mahasiswa.

Autoethnography has been used to examine employees’ physical and emotional experiences of workplace bullying and mobbing. In this approach of inquiry, data were extracted through; personal narrativ...

Background The long-term cardiovascular (CV) outcomes of COVID-19 have not been fully explored. Methods This was an international, multicenter, retrospective cohort study conducted between February and December 2020. Consecutive patients ≥18 years who underwent a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV2 were included. Patients were classified into two cohorts depending on the nasopharyngeal swab result and clinical status: confirmed COVID-19 (positive RT-PCR) and control (without suggestive symptoms and negative RT-PCR). Data were obtained from electronic records, and clinical follow-up was performed at 1-year. The primary outcome was CV death at 1-year. Secondary outcomes included arterial thrombotic events (ATE), venous thromboembolism (VTE), and serious cardiac arrhythmias. An independent clinical event committee adjudicated events. A Cox proportional hazards model adjusted for all baseline characteristics was used for comparing outcomes between groups. A prespecified landmark analysis was performed to assess events during the post-acute phase (31–365 days). Results A total of 4,427 patients were included: 3,578 (80.8%) in the COVID-19 and 849 (19.2%) control cohorts. At one year, there were no significant differences in the primary endpoint of CV death between the COVID-19 and control cohorts (1.4% vs. 0.8%; HRadj 1.28 [0.56–2.91]; p = 0.555), but there was a higher risk of all-cause death (17.8% vs. 4.0%; HRadj 2.82 [1.99–4.0]; p = 0.001). COVID-19 cohort had higher rates of ATE (2.5% vs. 0.8%, HRadj 2.26 [1.02–4.99]; p = 0.044), VTE (3.7% vs. 0.4%, HRadj 9.33 [2.93–29.70]; p = 0.001), and serious cardiac arrhythmias (2.5% vs. 0.6%, HRadj 3.37 [1.35–8.46]; p = 0.010). During the post-acute phase, there were no significant differences in CV death (0.6% vs. 0.7%; HRadj 0.67 [0.25–1.80]; p = 0.425), but there was a higher risk of deep vein thrombosis (0.6% vs. 0.0%; p = 0.028). Re-hospitalization rate was lower in the COVID-19 cohort compared to the control cohort (13.9% vs. 20.6%; p = 0.001). Conclusions At 1-year, patients with COVID-19 experienced an increased risk of all-cause death and adverse CV events, including ATE, VTE, and serious cardiac arrhythmias, but not CV death. Study registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT04359927.

Background and aim Measurement of cardiac index (CI) is crucial in the hemodynamic assessment of critically ill patients in the intensive care unit (ICU). The most reliable trans-thoracic echocardiography (TTE) technique for CI estimation is the left ventricular outflow tract (LVOT) Doppler method that requires, among other parameters, the LVOT cross-sectional area (CSA) measurement. However, geometrical assumptions inherent limitations and practical disadvantages related to the ICU setting, hamper LVOT-CSA assessment. In this study, we aimed to validate a simplified formula, leveraging only on LVOT-velocity time integral (VTI) and heart rate (HR) variables, for the non-invasive estimation of CI in ICU patients. Methods and Results We prospectively enrolled 50 consecutive patients admitted to our ICU requiring PAC over a one-year period. For each patient we measured the CI by PAC (CIPAC) and TTE. The latter was obtained both with the “traditional formula” (traditional CITTE), requiring LVOT-CSA assessment, and our new “simplified formula” (simplified CITTE). The correlation between the simplified CITTE and CIPAC was strong (r = 0.81) and resulted significantly greater than the traditional CITTE and CIPAC correlation (r = 0.70; p < 0.05 for Pearson r coefficients comparison). Both TTE-based CI showed an acceptable agreement (+0.19±0.48 L/min/m2 for simplified CITTE and -0.18±0.58 L/min/m2 for traditional CITTE) with the reference CIPAC. Conclusion In this study, we propose an easy-to-use and practical approach, leveraging on TTE LVOT-VTI and HR only, for non-invasive estimation of CI in ICU patients.

Measurement of cardiac index (CI) is crucial in the hemodynamic assessment of critically ill patients in the intensive care unit (ICU). The most reliable trans-thoracic echocardiography (TTE) technique for CI estimation is the left ventricular outflow tract (LVOT) Doppler method that requires, among other parameters, the LVOT cross-sectional area (CSA) measurement. However, inherent and practical disadvantages, mostly related to the ICU setting, hamper LVOT-CSA assessment. In this study, we aimed to validate a simplified formula, leveraging on LVOT-velocity time integral (VTI) and heart rate (HR) only, for non-invasive estimation of CI in ICU patients.We prospectively enrolled 50 consecutive patients admitted to our ICU requiring pulmonary artery catheterization (PAC) over a one-year period. For each patient we measured the CI by PAC (CIIn this study, we validated a practical approach, leveraging on TTE LVOT-VTI and HR only, for non-invasive estimation of CI in ICU patients.

Background and Objectives: Despite a well-established universal HIV diagnosis and treatment program, Botswana continues to face a high HIV prevalence, in large part due to persistent stigma, which particularly affects pregnant women and interferes with healthcare engagement. Tackling stigma as a fundamental cause of HIV disparities is an important but understudied aspect of current HIV interventions. Our multinational and multicultural team used a theory-driven, multi-stage iterative process to develop measures and interventions to first identify and then target the most culturally-salient aspects of stigma for mothers living with HIV in Botswana. This methodology report examines the stage-by-stage application of the “What Matters Most” (WMM) theory and lessons learned, sharing a replicable template for developing culturally-shaped anti-stigma interventions. Methods: First, we conducted initial qualitative work based on the WMM theory to identify key structural and cultural factors shaping stigma for women living with HIV in Botswana. Second, we developed a psychometrically validated scale measuring how “what matters most” contributes to and protects against stigma for this population. Third, we designed an anti-stigma intervention, “Mothers Moving towards Empowerment” (MME), centered on the local values identified using WMM theory that underly empowerment and motherhood by adapting a cognitive behavioral therapy (CBT)-informed, group-based, and peer-co-led anti-stigma intervention specifically for pregnant women living with HIV. Fourth, we conducted a pilot study of MME in which participants were allocated to two trial arms: intervention or treatment-as-usual control. Results: Our qualitative research identified that bearing and caring for children are capabilities essential to the concept of respected womanhood, which can be threatened by a real or perceived HIV diagnosis. These values informed the development and validation of a scale to measure these culturally-salient aspects of stigma for women living with HIV in Botswana. These findings further informed our intervention adaptation and pilot evaluation, in which the intervention group showed significant decreases in HIV stigma and depressive symptoms compared to the control group. Participants reported overcoming reluctance to disclose their HIV status to family, leading to improved social support. Conclusion and Global Health Implications: Previous studies have not utilized culturally-based approaches to assess, resist, and intervene with HIV-related stigma. By applying WMM in each stage, we identified cultural and gendered differences that enabled participants to resist HIV stigma. Focusing on these capabilities that enable full personhood, we developed an effective culturally-tailored anti-stigma intervention for pregnant women living with HIV in Botswana. This theory-driven, multi-stage approach can be replicated to achieve stigma reduction for other outcomes, populations, and contexts. Copyright © 2022 Poku et al. Published by Global Health and Education Projects, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution License CC BY 4.0.

Protein tyrosine phosphatases (PTPs) are the group of enzymes that control both cellular activity and the dephosphorylation of tyrosine (Tyr)-phosphorylated proteins. Dysregulation of PTP1B has contributed to numerous diseases including Diabetes Mellitus, Alzheimer’s disease, and obesity rendering PTP1B as a legitimate target for therapeutic applications. However, it is highly challenging to target this enzyme because of its highly conserved and positively charged active-site pocket motivating researchers to find novel lead compounds against it. The present work makes use of an integrated approach combining ligand based and structure-based virtual screening to find hit compounds targeting PTP1B. Initially, pharmacophore modelling was performed to find common features like two hydrogen bond acceptors, an aromatic ring and one hydrogen bond donor from the ligands with reported inhibition activity against PTP1B. The dataset of compounds matching with the common pharmacophoric features was filtered to remove Pan-Assay Interference substructure and to match the Lipinski criteria. Then, compounds were further prioritized using molecular docking and top fifty compounds with good binding affinity were selected for ADME predictions. The top five compounds with high solubility, absorption and permeability holding score of -10 to -9.3 kcal/mol along with Ertiprotafib were submitted to all-atom molecular dynamic (MD) studies. The MD studies and binding free energy calculations showed that compound M4, M5 and M8 were having better binding affinity for PTP1B enzyme with ∆Gtotal score of -24.25, -31.47 and -33.81 kcal/mol respectively than other compounds indicating that compound M8 could be a suitable lead compound for PTP1B enzyme inhibition.

The complexity of neurodegenerative diseases, among which Alzheimer's disease plays a pivotal role, poses one of the tough therapeutic challenges of present time. In this perspective, a multitarget approach appears as a promising strategy to simultaneously interfere with different defective pathways. In this paper, a structural simplification plan was performed on our previously reported multipotent polycyclic compounds, in order to obtain a simpler pharmacophoric central core with improved pharmacokinetic properties, while maintaining the modulating activity on neuronal calcium channels and glycogen synthase kinase 3-beta (GSK-3β), as validated targets to combat Alzheimer's disease. The molecular pruning approach applied here led to tetrahydroisoindole-dione (1), tetrahydromethanoisoindole-dione (2) and tetrahydroepoxyisoindole-dione (3) structures, easily affordable by Diels-Alder cycloaddition. Preliminary data indicated structure 3 as the most appropriate, thus a SAR study was performed by introducing different substituents, selected on the basis of the commercial availability of the furan derivatives required for the synthetic procedure. The results indicated compound 10 as a promising, structurally atypical, safe and BBB-penetrating Cav modulator, inhibiting both L- and N-calcium channels, likely responsible for the Ca2+ overload observed in Alzheimer's disease. In a multitarget perspective, compound 11 appeared as an effective prototype, endowed with improved Cav inhibitory activity, with respect to the reference drug nifedipine, and encouraging modulating activity on GSK-3β.

Despite the significant outcomes attained by scientific research, breast cancer (BC) still represents the second leading cause of death in women. Estrogen receptor-positive (ER+) BC accounts for the majority of diagnosed BCs, highlighting the disruption of estrogenic signalling as target for first-line treatment. This goal is presently pursued by inhibiting aromatase (AR) enzyme or by modulating Estrogen Receptor (ER) α. An appealing strategy for fighting BC and reducing side effects and resistance issues may lie in the design of multifunctional compounds able to simultaneously target AR and ER. In this paper, previously reported flavonoid-related potent AR inhibitors were suitably modified with the aim of also targeting ERα. As a result, homoisoflavone derivatives 3b and 4a emerged as well-balanced submicromolar dual acting compounds. An extensive computational study was then performed to gain insights into the interactions the best compounds established with the two targets. This study highlighted the feasibility of switching from single-target compounds to balanced dual-acting agents, confirming that a multi-target approach may represent a valid therapeutic option to counteract ER+ BC. The homoisoflavone core emerged as a valuable natural-inspired scaffold for the design of multifunctional compounds.

Introduction: The disease caused by the SARS-CoV-2 virus (COVID-19) frequently leads to serious complications and prolonged hospitalizations requiring effective care after discharge. Aim of the study: Aim of this study was to identify feasible and cost-effective predictors of outcome among clinical characteristics, functional status, laboratory, echocardiographic and lung ultrasound data of COVID-19 patients. Material and methods: Patients affected by COVID-19 who experienced a prolonged hospitalization due to a severe form of the disease and that have been discharged from the COVID-19 rehabilitation unit (RU) were prospectively enrolled between April 6th and May 22nd, 2020. All the patients underwent a 6-minute walk test (6MWT) at the 30-day follow-up. Baseline characteristics, laboratory, functional exercise tests, echocardiographic and lung ultrasound (LUS) data collected between hospitalization, admission to RU, discharge from RU and follow-up were compared. Correlations with the predicted distance covered at the 6MWT (6MWD) were made. Results: 40 patients met inclusion criteria and presented to follow-up (13 women [32.5%] and 27 men [67.5%]; mean age 66 ± 10 years). Among all variables analysed, only functional tests at discharge showed a remarkable correlation with the 6MWD. Significant improvement in lung ultrasound score (LUSS) was also observed however without correlation with 6MWD. Conclusions: functional tests at discharge from RU identified patients with different 30-day outcomes that could deserve a stricter long-term follow-up. This may help in planning a personalized follow-up. The costs and effort were minimal. The severity of the acute phase did not significantly influence functional recovery. LUS was useful to identify subclinical lung damage and its evolution over time, however without clear functional correlation.

The degree of social acceptance of biogas as a renewable green energy source is still somewhat disregarded. Although many initiatives have focused on the construction of new biogas plants around the world, local protests on the construction of new plants often arise. This study aims to analyse the determinants of citizens' perceptions regarding the construction of new biomass plants in their neighbouring areas. In particular, the focus is on prior knowledge of the production process of biogas as well as on other individual characteristics. The investigation is based on two repeated surveys conducted among the population living in two Italian areas where the construction of new large biogas plants were planned (the provinces of Oristano and Andria). The first survey analyses the main variables correlated with the degree of biogas acceptability particularly the biogas knowledge. The second survey (differentiated in two waves) focuses on the role of participatory processes and information campaigns undertaken by policy makers and environmental associations to increase the social acceptance of communities regarding the construction of new biogas plants.

Objectives. To explore whether beneficial health care policies, when implemented in the context of gender inequality, yield unintended structural consequences that stigmatize and ostracize women with HIV from “what matters most” in local culture. Methods. We conducted 46 in-depth interviews and 5 focus groups (38 individuals) with men and women living with and without HIV in Gaborone, Botswana, in 2017. Results. Cultural imperatives to bear children bring pregnant women into contact with free antenatal services including routine HIV testing, where their HIV status is discovered before their male partners’. National HIV policies have therefore unintentionally reinforced disadvantage among women with HIV, whereby men delay or avoid testing by using their partner’s status as a proxy for their own, thus facilitating blame toward women diagnosed with HIV. Gossip then defines these women as “promiscuous” and as violating the essence of womanhood. We identified cultural and structural ways to resist stigma for these women. Conclusions. Necessary HIV testing during antenatal care has inadvertently perpetuated a structural vulnerability that propagates stigma toward women. Individual- and structural-level interventions can address stigma unintentionally reinforced by health care policies.

Urbanization and human activities create new suitable aquatic habitats for the immature stages of mosquitoes in many countries. This also applies to Doi Inthanon National Park in northern Thailand, which is named for the highest mountain in the country. Despite its popularity, there is no information regarding mosquito diversity and community structure in the different ecosystems of the park. Monthly collections of immature stages from various habitats were conducted from August 2004 to December 2005 using dipping and sucking methods. The specimens collected from each habitat were reared to adults and identified based on their morphology. Diversity parameters and community structure were statistically analyzed. A total of 140 species (3795 specimens) belonging to 15 genera were identified. Among these, four genera (Culex, Aedes, Anopheles, and Uranotaenia) had high species richness, each represented by 48, 27, 19, and 15 species, respectively. Aedes albopictus was the most relatively abundant species, representing 6.7% of the total number of captured specimens, followed by Tripteroides aranoides (5.6%) and Cx. mimulus (5%). Species richness in natural habitats was significantly higher than in artificial containers. Species richness and abundance were highest in the rainy season. In comparison to agricultural areas and villages, mosquito diversity was found to be higher in forest areas. Ground pools, stream pools, rock pools, bamboo stumps, bamboo internode, and rice fields were the most preferred natural habitats. The results indicate that Doi Inthanon National Park has a high mosquito diversity. Each species exhibits differences in abundance and distribution in different habitats, which is useful information for planning conservation measures and vector control in the park.

During transcatheter edge-to-edge repair (TEER), the reduction of functional mitral regurgitation (FMR) severity, compared with baseline evaluation, is not uncommon. Because the procedural strategies are mainly guided by the location and severity of the regurgitant jets, intraprocedural downgrading (ID) of regurgitation severity could affect the procedural strategy and the results. The aim of this study was to evaluate the prevalence of ID during TEER and to compare early and midterm outcomes in patients with and without ID. All patients with moderate-to-severe or severe FMR who underwent TEER in San Raffaele Hospital between 2018 and 2020 were evaluated in this single-center, retrospective study. ID was defined as mild (1+) or moderate (2+) regurgitation degree during intraprocedural evaluation. The outcomes, assessed at discharge and at 2 years of follow-up, were all-cause mortality, heart failure hospitalization, and recurrence of mitral regurgitation2+. The final study cohort included 55 patients: 42% presented with ID. At discharge, 85.5% of patients achieved regurgitation reduction to 2+ or less: 100% in patients with ID versus 75% in patients without ID, p0.009. At 2 years, no significant difference in the incidence of all-cause mortality, heart failure hospitalization, and the recurrence of mitral regurgitation2+ between patients with ID or without ID was found. In conclusion, ID is frequent during TEER in FMR. No baseline characteristics were found to identify this group of patients. In patients with ID, the combination of live intraprocedural imaging and baseline ambulatory assessment of regurgitant jets seems effective in the procedural guiding to achieve a successful and durable mitral repair.

XXVII National Spectroscopy Meeting / XI Iberian Spectroscopy Conference, Málaga from 5 to 8 of July 2022., Support for this work was provided by Ministerio de Economía, Industria y Competitividad de España (project FIS2017-84318-R) and Comunidad de Madrid/EU (project TOP Heritage). MR acknowledges financial support from Sapienza University of Rome for the thesis abroad.

Photothermal therapy (PTT) is one of recently emerging anticancer treatment modalities that involve the use of laser and photosensitizers. To fully explore the therapeutic potential of PTT, it is critical to deliver photosensitizers to tumors specifically. Maltodextrin is a hydrophilic polysaccharide consisting of D-glucose units and has been used as a pharmaceutical excipient because of its excellent biocompatibility. IR820 is a derivative of indocyanine green (ICG), a clinically used imaging agent and has potential as a photosensitizer for PTT. However, the clinical translation of IR820 has been limited by its lack of cancer targeting ability and poor stability in physiological environments. In this study, we hypothesized that IR820-conjugated maltodextrin (MDir) preferentially accumulates in tumors and serves as photothermal agents. Combination of MDir and near-infrared (NIR) laser irradiation significantly increased the temperature, leading to photothermal-mediated apoptosis of cancer cells. In a mouse xenograft models, MDir preferentially accumulated in tumors and induced almost complete thermal ablation of tumors upon NIR laser irradiation. Based on its tumor targeting ability, photothermal conversion efficiency and excellent biocompatibility, we anticipate that MDir holds great translational potential as a fluorescence imaging-guided photothermal agent for cancer treatment.

Breast Cancer (BC) is a leading cause of death in women, currently affecting 13% of female population worldwide. First-line clinical treatments against Estrogen Receptor positive (ER+) BC rely on suppressing estrogen production, by inhibiting the aromatase (AR) enzyme, or on blocking estrogen-dependent pro-oncogenic signaling, by targeting Estrogen Receptor (ER) α with selective Modulators/Degraders (SERMs/SERDs). The development of dual acting molecules targeting AR and ERα represents a tantalizing alternative strategy to fight ER + BC, reducing the incidence of adverse effects and resistance onset that limit the effectiveness of these gold-standard therapies. Here, in silico design, synthesis, biological evaluation and an atomic-level characterization of the binding and inhibition mechanism of twelve structurally related drug-candidates enable the discovery of multiple compounds active on both AR and ERα in the sub-μM range. The best drug-candidate 3a displayed a balanced low-nanomolar IC50 towards the two targets, SERM activity and moderate selectivity towards a BC cell line. Moreover, most of the studied compounds reduced ERα levels, suggesting a potential SERD activity. This study dissects the key structural traits needed to obtain optimal dual acting drug-candidates, showing that multitarget compounds may be a viable therapeutic option to counteract ER + BC.

Despite a comprehensive national program of free HIV services, men living with HIV in Botswana participate at lower rates and have worse outcomes than women. Directed content analysis of five focus groups ( n = 38) and 50 in-depth interviews with men and women with known and unknown HIV status in Gaborone, Botswana in 2017 used the “what matters most” (WMM) and “structural vulnerability” frameworks to examine how the most valued cultural aspects of manhood interact with HIV-related stigma. WMM for manhood in Botswana included fulfilling male responsibilities by being a capable provider and maintaining social status. Being identified with HIV threatened WMM, which fear of employment discrimination could further exacerbate. Our findings indicate how cultural and structural forces interact to worsen or mitigate HIV-related stigma for urban men in Botswana. These threats to manhood deter HIV testing and treatment, but interventions could capitalize on cultural capabilities for manhood to promote stigma resistance.

We conducted a pilot trial of an intervention targeting intersectional stigma related to being pregnant and living with HIV while promoting capabilities for achieving ‘respected motherhood’ (‘what matters most’) in Botswana. A pragmatic design allocated participants to the intervention (N = 44) group and the treatment-as-usual (N = 15) group. An intent-to-treat, difference-in-difference analysis found the intervention group had significant decreases in HIV stigma (d = − 1.20; 95% CI − 1.99, − 0.39) and depressive symptoms (d = − 1.96; 95% CI − 2.89, − 1.02) from baseline to 4-months postpartum. Some, albeit less pronounced, changes in intersectional stigma were observed, suggesting the importance of structural-level intervention components to reduce intersectional stigma.

Naturally occurring flavonoids are found as secondary metabolites in a wide number of plants exploited for both medicine and food and have long been known to be endowed with multiple biological activities, making them useful tools for the treatment of different pathologies. Due to the versatility of the scaffolds and the vast possibilities of appropriate decoration, they have also been regarded as fruitful sources of lead compounds and excellent chemical platforms for the development of bioactive synthetic compounds. Flavone-8-acetic acid (FAA) and 5,6-dimethylxanthone acetic acid (DMXAA) emerged for their antitumour potential due to the induction of cytokines and consequent rapid haemorrhagic necrosis of murine tumour vasculature, and different series of derivatives have been designed thereafter. Although the promising DMXAA failed in phase III clinical trials because of strict species-specificity, a boost in research came from the recent identification of the stimulator of interferon genes (STING), responsible for supporting tumoural innate immune responses, as a possible biological target. Consequently, in the last decade a renewal of interest for these flavonoid-based structures was noticed, and novel derivatives have been synthesised and evaluated for a deeper understanding of the molecular features needed for affecting human cells. Undoubtedly, these natural-derived molecules deserve further investigation and still appear attractive in an anticancer perspective.

To address the multifactorial nature of Alzheimer's Disease (AD), a multi-target-directed ligand approach was herein developed. As a follow-up of our previous studies, a small library of newly designed 2-arylbenzofuran derivatives was evaluated towards cholinesterases and cannabinoid receptors. The two most promising compounds, 8 and 10, were then assessed for their neuroprotective activity and for their ability to modulate the microglial phenotype. Compound 8 emerged as able to fight AD from several directions: it restored the cholinergic system by inhibiting butyrylcholinesterase, showed neuroprotective activity against A beta(1-42) oligomers, was a potent and selective CB2 ligand and had immunomodulatory effects, switching microglia from the pro-inflammatory M1 to the neuroprotective M2 phenotype. Derivative 10 was a potent CB2 inverse agonist with promising immunomodulatory properties and could be considered as a tool for investigating the role of CB2 receptors and for developing potential immunomodulating drugs addressing the endocannabinoid system. (C) 2019 Elsevier Masson SAS. All rights reserved.

[Image: see text] The discovery of the relevant role played by a dysregulation of the endogenous cannabinoid system in several pathological conditions has prompted an extensive research in this field. In this Letter, a series of cannabinoid receptor ligands bearing a previously unexplored polycyclic scaffold was designed and synthesized, in order to evaluate the potential of a new easily affordable privileged structure. The new compounds showed an appreciable affinity and a significant selectivity for the CB2 receptor and are endowed with an intriguing noncompetitive antagonist behavior. Due to the ability of the polycyclic structure to be easily modified in different ways, these compounds could represent convenient chemical tools to be exploited in order to better understand the endocannabinoid system impact on physiopathological conditions.

Most of the indoor coverage issues arise from network deployments that are usually planned for outdoor scenarios. Moreover, the ever-growing number of devices with different Radio Access Technologies (RATs), expected for new 5G scenarios and to maintain compatibility with older cellular standards (mostly 3G/4G), worsen this situation thus calling for novel bandwidth-efficient, low-latency and cost-effective solutions for indoor coverage. To solve this problem, Centralized Radio Access Network (C-RAN) architectures have been proposed to provide dense and controlled coverage inside buildings. However, all-digital C-RAN solutions are complex and expensive when indoor layout constraints and device costs are considered. We discuss here an analog C-RAN architecture, referred to as Analog MIMO Radio-over-Copper (A-MIMO-RoC), that aims at distributing RF signals indoors over distances in the order of 50 m. The all-analog passive-only design presented here proves the feasibility of analog relaying of MIMO radio signals over LAN cables at frequency bandwidth values up to 400 MHz for multi-RAT applications. After asserting the feasibility of the A-MIMO-RoC platform, we present some experimental results obtained with the proposed architecture. These preliminary results show that the A-MIMO-RoC system is a valid solution towards the design of dedicated 4G/5G indoor wireless systems for the billions of buildings which nowadays still suffer from severe indoor coverage issues., Part of this work has been accepted in IEEE TCAS II