Maintenance Phase Research Articles

Is the Absence of Manual Lymphatic Drainage-Based Treatment in Lymphedema after Breast Cancer Harmful? A Randomized Crossover Study.

(1) Background: Manual lymphatic drainage (MLD), included within the complex decongestive therapy, as a therapy for the treatment of lymphedema has raised controversy about its benefits for lymphedema after breast cancer. The aim of this research is to test the effects of MLD on lymphedema after breast cancer during the treatment maintenance phase. (2) Methods: A randomized, single-blinded, controlled crossover trial was conducted to analyze the effects of a manual lymphatic drainage intervention compared to a control group without MLD intervention for the treatment of lymphedema. Arm volume measured by circumference measurement, subcutaneous tissue thickness measured by ultrasound, and the sensation of pain, heaviness, and swelling were evaluated as outcome measures. (3) Results: For the control group, an increase in volume was found in some of the circumference and subcutaneous tissue thickness measurements, in addition to a worsening of arm pain, swelling and heaviness. (4) Conclusion: The absence of treatment based on MLD in lymphedema after breast cancer worsens volume measurements, as well as arm heaviness. Therefore, it would be advisable to carry out this type of therapy as part of the maintenance treatment for lymphedema in breast cancer.

Model-based, fully simulated, system-level power consumption estimation of IoT devices

Internet of things (IoT) gaining more importance due to its crucial role in pervasive computing and also Industry 4.0. Since the number of IoT devices is scaling up to multiple dozens of billions, the importance of energy efficiency is significantly increased. With the consideration of huge variety of IoT device hardware and software, a comprehensive model and estimation methodology on energy consumption is necessary as an enabler. IoT devices are also frequently updated, upgraded and maintained because of the evolving nature of the requirements and market demands. Each and every such operation has an effect on the power consumption and arose the necessity for a new energy consumption modeling and estimation. This process is applicable for development of IoT devices, as well as the maintenance phase. Since the variety of designs is unlimited, and battery capacity is usually fixed, or a cost factor, a generic, fully simulated, model-based energy consumption estimation of IoT devices is crucial. In this study, we aim to address this problem via proposing fully simulated, model-based, system-level power estimation approaches, as well as their success rate in typical real-life scenarios. It can be seen that the proposed methodology has high accuracy over %97. For the realization of the best-proposed approach, we used Open Virtual Platform (OVP) as an instruction set accurate simulator.

ASAM recommends higher doses if needed for treatment with buprenorphine

In a clear but measured and scientific dispute against standard practice today, the American Society of Addiction Medicine (ASAM) has called for an end to the standardization of doses of buprenorphine for opioid use disorder (OUD). The recommendations, published in the Journal of Addiction Medicine, ASAM's flagship journal, note that doses should be optimal based on the individual needs of the patient. This was never in question within medical circles, including ASAM, but insurance policies and the tyranny of what is expected have led to suboptimal doses, both in the induction phase and the maintenance phase, of treatment.

The effect of CNQX on self-administration: present in nicotine, absent in methamphetamine model.

Addiction is a chronic disease with limited pharmacological options for intervention. Focusing on reducing glutamate levels in the brain seems to be a promising strategy in addiction treatment research. Our research aimed to evaluate the effects of CNQX, an antagonist that targets AMPA and kainate glutamatergic receptors while also exhibiting affinity for the NMDA receptor, especially by modulating its glycine site. We conducted this assessment on the self-administration of nicotine and methamphetamine via intravenous (IV) administration in rats. An operant IV self-administration model was used in male Wistar rats. When animals maintained a stable intake of nicotine or methamphetamine, we administered a single injection of CNQX (in the dose of 3 or 6 mg/kg IV) to evaluate its effect on drug intake. Subsequently, the rats were forced to abstain by staying in their home cages for 2 weeks. The period of abstinence was followed by a context-induced relapse-like session before which animals were pretreated with the injection of CNQX (3 or 6 mg/kg IV) to evaluate its effect on drug seeking. CNQX significantly reduced nicotine intake during the maintenance phase, but no effect was revealed on nicotine seeking after forced abstinence. CNQX did not affect methamphetamine taking or seeking. The effect of reducing nicotine taking but not seeking could be explained by different involvement of glutamatergic receptors in various stages of nicotine dependence.

A Retrospective Study on tDCS Treatment in Patients with Drug-Resistant Chronic Pain.

Background. Transcranial direct current stimulation (tDCS) of the primary motor cortex (M1) has an analgesic effect superior to a placebo in chronic pain. Some years ago, tDCS was implemented at the Hospital Nacional of Paraplegics (Toledo, Spain) to treat patients with pharmacological resistance to chronic pain. Objective. The main objectives of this study with tDCS were (1) to confirm the safety of one-year treatment; (2) to estimate the number of patients after one year in treatment; (3) to describe the effects of tDCS on the pain intensity during one-year treatment; and (4) to identify factors related to treatment success. Methods. This was a retrospective study conducted at the National Hospital for Paraplegics with 155 patients with pharmacologically resistant chronic pain. Anodal tDCS was applied over the M1 for 20 min at 1.5 mA for 10 treatment sessions from Monday to Friday (Induction phase), followed by 2-3 sessions per month (Maintenance phase). Pain intensity was assessed using a Visual Analogue Scale (VAS). Results. Anodal tDCS on M1 confirmed the reduction in the pain intensity. Moreover, 58% of outpatients completed one year of treatment. Only the VAS values obtained during the baseline influenced the response to treatment. Patients with a very high VAS at the baseline were more likely to not respond adequately to tDCS treatment. Conclusions. Anodal tDCS over M1 is an adequate therapy (safe and efficient) to treat drug-resistant chronic pain. Moreover, pain intensity at the start of treatment could be a predictor of patients' continuity with tDCS for at least one year.

Combinatorial Hypofractionated Radiotherapy and Pembrolizumab in Anaplastic Thyroid Cancer.

Objectives Anaplastic thyroid cancer (ATC) is an aggressive disease associated with poor outcomes and resistance to therapies. Our study aim was to evaluate the activity of a combinatorial regimen of sandwich sequencing of pembrolizumab immunotherapy and hypofractionated radiotherapy (RT). Methods In this case series, patients with ATC received hypofractionated RT (QUAD-shot) and intravenous pembrolizumab 200mg every 3-4 weeks. Pembrolizumab was continued until disease progression or up till 24 months. Concurrent Lenvatinib treatment was allowed. Primary endpoint was best overall response (BOR) and progression-free survival (PFS). Additionally, we performed immune profiling of circulating T cells in a responder to investigate the immune response to our combinatorial treatment. Results At median follow-up of 32.6 months (IQR: 26.4-38.8), of a cohort of 5 patients, BOR was 80%; with 2 complete responses (CR) and 2 partial responses (PR). Patients who achieved CR remained disease-free at last follow-up. Median PFS was 7.6 months (IQR: 6.2-NR), and 1-year PFS and overall survival rate was 40% (95% CI: 13.7-100) for both. Treatment was well-tolerated, with mostly grade 1-2 adverse events. Immune profiling of one partial responder revealed an increase in activated CD4 and CD8 T cells post-QUAD-shot RT, which was further enhanced during the maintenance phase of pembrolizumab. Conclusions Herein, we reported a case series of 5 patients with ATC, with 2 long-term survivors who were treated with surgical debulking followed by QUAD-shot RT and pembrolizumab, possibly due to synergy of local and systemic treatments in activating anti-tumour immunogenic cytotoxicity. This regimen warrants further investigation in a larger cohort of patients.

Effects of small community walking intervention on physical activity, well-being, and social capital among older patients with cardiovascular disease in the maintenance phase: a randomized controlled trial.

[Purpose] Older patients with cardiovascular disease should increase their physical activity and prioritize positive psychological and social approaches in the maintenance phase of their cardiac rehabilitation. This study aimed to clarify the effect of small community walking on physical activity, well-being, and social capital in older patients with cardiovascular disease in the maintenance phase. [Participants and Methods] We conducted a multicenter study in Kumamoto, Japan. We randomly divided 55 patients with cardiovascular disease into two groups: small community walking and walking alone. For three months, a registered cardiac rehabilitation instructor provided walking guidance to both groups using a wearable device. We measured physical activity, social capital, and subjective happiness before and after the intervention. [Results] Results revealed a statistically significant main effect of time on physical activity and social participation. In the subjective happiness scale, there was an association between group and time. [Conclusion] Our results suggest that walking guidance using a wearable device was beneficial in improving overall physical activity, regardless of whether the individual did small community walking or walking alone. Furthermore, small community walking intervention may effectively enhance well-being. The relationship between physical activity and social participation needs to be further investigated.

Developing an integrative framework for digital twin applications in the building construction industry: A systematic literature review

In response to the global advocacy for digitalization, numerous industrial sectors are actively advancing the implementation of digital twins (DTs). However, the construction industry has been slow to adopt DT, lagging behind sectors such as manufacturing and medicine, where digitalization has made significant strides. Given the demonstrated benefits and potential of DT, it is crucial to increase research efforts for enhancing its application in the construction industry. To accurately identify prospective areas for future research, a comprehensive review and analysis of the status quo of relevant research is urgently needed. This study undertook a systematic literature review to understand how DT can enhance operational intelligence in the building construction industry. The findings, based on a review of pertinent literature, revealed that existing studies predominantly focused on the application of DT during the construction phase and the operation and maintenance phase. However, its potential use during the planning and design phase and the demolition and recovery phase was largely overlooked. Three main categories of key digital facilitating technologies for DT in the building construction industry have been identified: (1) data-related technologies; (2) high-fidelity modeling technologies; and (3) model-based simulation technologies. These technologies have finally culminated into an integrative framework. Furthermore, three significant research gaps in the application of DT in the building construction industry have been identified, suggesting future studies explore how to (1) centralize diverse stakeholders from a lifecycle perspective; (2) address various existing technological defects; and (3) establish a universal industry standard. This paper provides a valuable roadmap for relevant stakeholders to understand the status quo of DT application and the existing deficiencies in its full implementation, which should facilitate the efficient digitalization of the construction industry.

A Conceptual Analysis of Post-psychotic Depression

"The conundrum of post-psychotic depression (PPD) is still present in the psychiatric literature, for more than a century since it was first described by Mayer-Gross. After a short existence in the DSM-IV and ICD-10, this nosological construct was excluded from newer versions of the mental disorders classifications. Therefore, an exploratory analysis of the PPD concept was considered useful both from clinical and theoretical perspectives. There is a high prevalence of depressive symptoms in patients with schizophrenia spectrum disorders (SSD) and, although not all of them represent cases of PPD, they are considered risk factors for suicide. The arguments and contra-arguments for/against PPD were reviewed, and the potential pharmacological interventions for this disorder were analyzed. The explored evidence indicates that PPD is worth further investigation, and in order to differentiate it from schizoaffective disorder, negative symptoms of SSD, or depressive manifestations within the acute psychotic episodes, clearly defined criteria should be found. The use of validated scales, like the Calgary Depression Scale for Schizophrenia and the InterSePT Scale for Suicidal Thinking, is recommended for the initial assessment of depression and suicidal risk in patients with SSD, but also for their monitoring during the acute and maintenance phases. Besides the administration of combined, antidepressant and antipsychotic treatment, the use of clozapine, and the recommendation to initiate treatment for SSD with atypical antipsychotics whenever possible, there is a dearth of studies exploring specific interventions for PPD. Future studies are expected to address the validity of the nosological construct of PPD and the most adequate therapeutic and prophylactic interventions in patients with SSD."

Severe pulmonary hypertension-interstitial lung disease presenting as right ventricular failure: stabilisation with intravenous prostacyclin and maintenance with inhaled prostacyclin.

Pulmonary hypertension (PH) leads to increased morbidity and mortality in interstitial lung disease (ILD). While the INCREASE trial highlighted the use of inhaled prostacyclin in PH-ILD patients, such therapy may be inadequate when right ventricular failure (RVF) is also present. In this study, we report the use of intravenous prostacyclin in three PH-ILD patients to stabilise right ventricular (RV) function, with a subsequent transition to maintenance therapy with inhaled prostacyclin. We evaluated three consecutive PH-ILD patients with RVF. RV afterload and pulmonary vascular resistance (PVR) were treated with intravenous prostacyclin during the induction phase of the therapy. Patients transitioned from intravenous prostacyclin to the maintenance phase of the treatment with inhaled prostacyclin once three transition criteria were met: cardiac index (CI) >2 L·min-1·m-2, PVR <7 Wood units (WU) and tricuspid annular plane systolic excursion (TAPSE) change >1 mm or TAPSE >1.6 cm. Pre-treatment parameters for the three patients were a mean PVR of 14.3 WU, a mean Fick CI of 1.8 L·min-1·m-2 and a mean TAPSE of 1.4 cm. The average intravenous prostacyclin dose at the time of transition to maintenance therapy was 20.7 ng·kg-1·m-2 of treprostinil. At 3-months follow-up, the mean PVR was 6.3 WU, Fick CI 2.2 L·min-1·m-2 and TAPSE 1.7 cm. This case series of three PH-ILD patients with RVF introduces the concept of an initial intravenous prostacyclin induction phase, followed by a transition to maintenance therapy with inhaled prostacyclin. Further development of this treatment algorithm with a refinement of the transition criteria, potential testing in a clinical trial and a longer-term follow-up period is warranted to improve the outcomes of advanced PH-ILD patients with concomitant RVF.

Sphingosine 1-phosphate (S1P) receptor modulators as an induction and maintenance therapy for ulcerative colitis: a systematic review and meta-analysis of randomized controlled trials.

One sphingosine-1-phosphate (S1P) receptor modulator is approved (ozanimod) and another (etrasimod) is under investigation for the induction and maintenance of remission of ulcerative colitis (UC). We aim to evaluate the efficacy and safety of S1P modulators in patients with active UC. We conducted a systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching: PubMed, Web of Science, SCOPUS, and Cochrane through May 13th, 2023. We used the fixed-effect model to pool dichotomous data using risk ratio (RR) with a 95% confidence interval (CI). Five RCTs with a total of 1990 patients were included. S1P receptor modulators were significantly associated with increased clinical response during both the induction (RR 1.71 with 95% CI [1.50, 1.94], P = 0.00001) and maintenance phases (RR 1.89 with 95% CI [1.33, 2.69], P = 0.0004); clinical remission rates during both induction (RR 2.76 with 95% CI [1.88, 4.05], P = 0.00001) and maintenance phases (RR 3.34 with 95% CI [1.41, 7.94], P = 0.006); endoscopic improvement during both induction (RR 2.15 with 95% CI [1.71, 2.70], P = 0.00001) and maintenance phases (RR 2.41 with 95% CI [1.15, 5.05], P = 0.02); and histologic remission during both induction (RR 2.60 with 95% CI [1.89, 3.57] [1.17, 2.10], P = 0.00001) and maintenance phases (RR 2.52 with 95% CI [1.89, 3.37], P = 0.00001). Finally, there was no difference regarding safety outcomes as compared to placebo in both the induction and maintenance phases. S1P receptor modulators are effective in inducing and maintaining remission in patients with moderate to severe UC.

THE DEVELOPMENT OF THE SENI CINTA WEBSITE, INCORPORATING METICULOUS PROCESSES IN DESIGN, DEVELOPMENT, AND THOROUGH EVALUATION OF USER EXPERIENCE

This in-depth investigation delves into the evolution of the web for the "Seni Cinta" book, also known as "Love Uses the Brain" in English. Seni Cinta is a digital platform in the Malay language that is dedicated to unravelling the intricate facets of love and love languages within various relationships, including those in families and friendships. Beyond static content, the website enriches user engagement by incorporating five unique personality tests, offering individuals profound insights into their distinct characteristics. Utilising the user-friendly WordPress platform, the website is a custom creation that does not require coding expertise. The primary aim of this study goes beyond exploration; it positions the website as a strategic tool to enlighten the target audience about their individual love personality types. Additionally, the website serves as a promotional gateway for the company's upcoming book, "Cinta Pakai Otak". To simplify the user experience, the platform facilitates seamless book orders, eliminating the need for prolonged account registrations and prioritising accessibility and efficiency. The methodology of the study unfolds through several phases, starting with the requirement phase and progressing through design, development, testing, and deployment, culminating in an ongoing maintenance phase. Client satisfaction with the Seni Cinta website validates the achievement of the primary goal: designing an interactive and user-friendly digital space. The successful integration of informative content, personality assessments, and streamlined book promotion underscores the effectiveness of this comprehensive approach, demonstrating its relevance in meeting the evolving needs of a diverse audience navigating the complexities of love and interpersonal dynamics.

A Modified Horse Herd Optimization Algorithm and Its Application in the Program Source Code Clustering

Maintenance is one of the costliest phases in the software development process. If architectural design models are accessible, software maintenance can be made more straightforward. When the software’s source code is the only available resource, comprehending the program profoundly impacts the costs associated with software maintenance. The primary objective of comprehending the source code is extracting information used during the software maintenance phase. Generating a structural model based on the program source code is an effective way of reducing overall software maintenance costs. Software module clustering is considered a tremendous reverse engineering technique for constructing structural design models from the program source code. The main objectives of clustering modules are to reduce the quantity of connections between clusters, increase connections within clusters, and improve the quality of clustering. Finding the perfect clustering model is considered an NP-complete problem, and many previous approaches had significant issues in addressing this problem, such as low success rates, instability, and poor modularization quality. This paper applied the horse herd optimization algorithm, a distinctive population-based and discrete metaheuristic technique, in clustering software modules. The proposed method’s effectiveness in addressing the module clustering problem was examined by ten real-world standard software test benchmarks. Based on the experimental data, the quality of the clustered models produced is approximately 3.219, with a standard deviation of 0.0718 across the ten benchmarks. The proposed method surpasses former methods in convergence, modularization quality, and result stability. Furthermore, the experimental results demonstrate the versatility of this approach in effectively addressing various real-world discrete optimization challenges.

Comparative cost analysis of traditional and industrialised deep retrofit scenarios for a residential building

In this paper, the economic competitiveness for deep retrofit actions between the industrialised off-site and the traditional on-site approaches are discussed by using a comparative Life Cycle Costing (LCC) analysis. This assessment was based on a deep analysis of all renovation-related cost and timing processes, from design to operation and maintenance phases. The study was based on three retrofit scenarios for an existing building in Italy undergoing a deep renovation. The Life Cycle Inventory (LCI) was developed starting from real costs and a list of bills collected by the design team and the industrialised technologies developers. Afterwards, the LCC modelling was performed for all scenarios. The results show that the two deep retrofit approaches (traditional and industrialised) are comparable in terms of investment costs, even if a gap of around -7% and +16% still exists. This highlights a potential for technological optimisation. Moreover, the operation and maintenance phase has shown to be key to transforming the expected higher quality of the industrialised components into a prolonged life expectance, hence highly impacting the whole cumulated Net Present Value. Finally, the analysis of the End of Life (EoL) phase in case of possible reusing of some dismantled components in the industrialised scenario resulted in contributing in a relevant way to increase the final value of such an approach.

Environment-Aware Adaptive Reinforcement Learning-Based Routing for Vehicular Ad Hoc Networks.

With the rapid development of the intelligent transportation system (ITS), routing in vehicular ad hoc networks (VANETs) has become a popular research topic. The high mobility of vehicles in urban streets poses serious challenges to routing protocols and has a significant impact on network performance. Existing topology-based routing is not suitable for highly dynamic VANETs, thereby making location-based routing protocols the preferred choice due to their scalability. However, the working environment of VANETs is complex and interference-prone. In wireless-network communication, the channel contention introduced by the high density of vehicles, coupled with urban structures, significantly increases the difficulty of designing high-quality communication protocols. In this context, compared to topology-based routing protocols, location-based geographic routing is widely employed in VANETs due to its avoidance of the route construction and maintenance phases. Considering the characteristics of VANETs, this paper proposes a novel environment-aware adaptive reinforcement routing (EARR) protocol aimed at establishing reliable connections between source and destination nodes. The protocol adopts periodic beacons to perceive and explore the surrounding environment, thereby constructing a local topology. By applying reinforcement learning to the vehicle network's route selection, it adaptively adjusts the Q table through the perception of multiple metrics from beacons, including vehicle speed, available bandwidth, signal-reception strength, etc., thereby assisting the selection of relay vehicles and alleviating the challenges posed by the high dynamics, shadow fading, and limited bandwidth in VANETs. The combination of reinforcement learning and beacons accelerates the establishment of end-to-end routes, thereby guiding each vehicle to choose the optimal next hop and forming suboptimal routes throughout the entire communication process. The adaptive adjustment feature of the protocol enables it to address sudden link interruptions, thereby enhancing communication reliability. In experiments, the EARR protocol demonstrates significant improvements across various performance metrics compared to existing routing protocols. Throughout the simulation process, the EARR protocol maintains a consistently high packet-delivery rate and throughput compared to other protocols, as well as demonstrates stable performance across various scenarios. Finally, the proposed protocol demonstrates relatively consistent standardized latency and low overhead in all experiments.

A longitudinal evaluation of smell and taste function in children with cancer during and after treatment with chemotherapy

Smell and taste changes are bothersome treatment symptoms interfering with food intake. It remains unclear how and when children with cancer experience such changes during chemotherapy, and if the symptoms resolve after treatment. In this longitudinal study, we measured smell and taste function of 94 childhood cancer patients treated for hematological, solid, or brain malignancies. Smell and taste function were assessed using commercial Sniffin’ Sticks and Taste Strips, respectively. For both tests, normative values were used to identify the presence of smell and taste abnormalities. Self-reported chemosensory and appetite changes were assessed using a questionnaire. Measurements were taken approximately 6 weeks (T0), 3 months (T1), 6 months after starting chemotherapy (T2), and 3 months after termination of chemotherapy or maintenance phase for children with acute lymphoblastic leukemia (ALL) (T3). We found that smell and taste scores did not change during active treatment (T0-2). However, approximately 20% of the patients suffered from decreased taste function according to normative values, particularly children with lymphoma or solid tumors. Changes in smell were predominantly characterized as increased rather than decreased. Self-reported changes were much more common than objectively measured, with smell changes ranging from 26 to 53% and taste changes up to 80% during treatment. After active treatment, odor threshold scores decreased in children with ALL during maintenance phase, whereas total taste scores increased in all children at T3. In summary, objectively measured smell and taste function remained stable during active treatment, while at the individual level a fairly large number of children suffered from chemosensory distortions which comprised either increased or decreased sensitivity. Individual dietary advice and coping strategies are warranted to prevent detrimental effects on food intake in children with cancer.

Traffic-Predictive Routing Strategy for Satellite Networks

To address the issues of uneven satellite network load and unstable link connections, a globally adaptive satellite network routing strategy based on traffic prediction (G-AODV) is proposed by enhancing the existing Ad hoc On-Demand Distance Vector Routing (AODV) protocol. To prevent heavily loaded nodes from becoming intermediate nodes, G-AODV introduces a traffic prediction mechanism in the route discovery phase. The routing request packet adopts the corresponding forwarding control policy based on the comparison between the predicted traffic load value at the next moment and the dynamic threshold. At the same time, a path replacement strategy is adopted to replace paths before node congestion occurs to achieve load balancing. Considering the unstable characteristics of the satellite chain that easily breaks, the route maintenance phase selects a path repair method by judging the node stability to avoid secondary breaks in the route. The simulation results show that in scenarios with different packet delivery rates, compared with the three comparative routing strategies, the packet delivery rate of G-AODV is increased by up to 20%, the packet loss rate is reduced by 22%, and the end-to-end delay is significantly reduced. In scenarios with different communication connection pairs, G-AODV’s packet delivery rate increased by up to 20%, the packet loss rate decreased by 18%, and the end-to-end delay was still reduced.

Empagliflozin and Rapid Kidney Function Decline Incidence in Type 2 Diabetes: An Exploratory Analysis From the EMPA-REG OUTCOME Trial

Kidney function progressively declines in most patients with type 2 diabetes (T2DM). Many develop progressive chronic kidney disease (CKD), but some experience a more rapid decline, with a greater risk of kidney failure and cardiovascular disease. In EMPA-REG OUTCOME, empagliflozin was associated with slower kidney disease progression. This post hoc analysis evaluated the effect of empagliflozin (pooled doses) on the prevalence of a "rapid decliner" phenotype, defined by an annual estimated glomerular filtration rate (eGFR) decline of>3mL/min/1.73m2. This was an exploratory analysis of EMPA-REG OUTCOME, a large randomized, double-blind, placebo-controlled trial in adults with T2DM, established cardiovascular disease and an eGFR of≥30mL/min/1.73m2. Analysis was undertaken on 6,967 participants (99.2%) in whom serial eGFR data was available. Patients were randomized (1:1:1) to empagliflozin 10mg, 25mg, or placebo in addition to standard of care. Annual change in eGFR over the maintenance phase of treatment (week 4 to last value on treatment) was calculated using linear regression models. Logistic regression analysis was used to investigate differences in rapid decline between the treatment groups. Over the study period, a rapid decliner phenotype was observed in 188 (9.5%) participants receiving placebo and 134 (3.4%) receiving empagliflozin. After adjusting for other risk factors, this equated to a two-third reduction in odds (OR, 0.32; 95% CI, 0.25-0.40; P<0.001) among participants receiving empagliflozin versus placebo. A comparable risk reduction was observed using a threshold of eGFR decline of>5mL/min/1.73m2/y (empagliflozin vs placebo, 43 [1.1%] vs 44 [2.2%] participants; OR, 0.47; 95% CI, 0.31-0.72; P<0.001). This is a post hoc analysis of a trial undertaken in participants with T2DM and CVD. Generalization of findings to other settings remains to be established. Patients receiving empagliflozin were significantly less likely to experience a rapid decline in eGFR over a median of 2.6 years of exposure to the study drug. The Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance. clinicaltrials.gov ID: NCT01131676.

Phase-specific differential regulation of mechanical allodynia in a murine model of neuropathic pain by progesterone.

Progesterone has been shown to have neuroprotective capabilities against a wide range of nervous system injuries, however there are negative clinical studies that have failed to demonstrate positive effects of progesterone therapy. Specifically, we looked into whether progesterone receptors or its metabolizing enzymes, cytochrome P450c17 and 5α-reductase, are involved in the effects of progesterone on neuropathic pain after chronic constriction injury (CCI) of the sciatic nerve in mice. Intrathecal progesterone administration during the induction phase of chronic pain enhanced mechanical allodynia development and spinal glial fibrillary acidic protein (GFAP) expression, and this enhancement was inhibited by administration of ketoconazole, a P450c17 inhibitor, but not finasteride, a 5α-reductase inhibitor. Furthermore, phospho-serine levels of P450c17 in the spinal cord were elevated on day 1 after CCI operation, but not on day 17. In contrast, intrathecal progesterone administration during the maintenance phase of chronic pain decreased the acquired pain and elevated GFAP expression; this inhibition was restored by finasteride administration, but not by ketoconazole. The modification of mechanical allodynia brought on by progesterone in CCI mice was unaffected by the administration of mifepristone, a progesterone receptor antagonist. Collectively, these findings imply that progesterone suppresses spinal astrocyte activation via 5α-reductase activity during the maintenance phase of chronic pain and has an analgesic impact on the mechanical allodynia associated with the growing neuropathy. Progesterone, however, stimulates spinal astrocytes during the induction stage of peripheral neuropathy and boosts the allodynic impact caused by CCI through early spinal P450c17 activation.

Trends and Challenges in Railway Sustainability: The State of the Art regarding Measures, Strategies, and Assessment Tools

Rail is expected to become the backbone of future mobility in the world as the cleanest and greenest high-volume transport. Rail generates the lowest CO2 emissions and energy consumption when in operation, with respect to the other transportation modes, but during construction and maintenance phases, its environmental impacts are significant and need to be carefully assessed and properly mitigated. This paper, through an extensive analysis of the recent literature, aims to provide a comprehensive framework of trends and challenges in railway sustainability, with particular attention paid to track and related materials and components, maintenance strategies, and methods of assessment of sustainability. The followed approach takes into consideration the lifespan of the track and the related main stages. The results show that: (i) several innovative sustainable materials have been introduced with significant environmental performances and limitations, mainly due to the lack of knowledge of long-term mechanical behavior; (ii) appropriate strategies of maintenance, supported by effective monitoring of the track conditions, can reduce negative effects on the environment and society and contribute to making this transportation mode greener; (iii) many devices for the automated detection of the track defects allow increasingly widespread and effective monitoring of the track and are essential means in overcoming the challenge of “smart rails”; and (iv) life cycle assessment (LCA) and circularity metrics are effective and indispensable tools in the decision-making process, since they help to quantify the potential environmental enhancement of different materials and solutions.