Assessment of climate change on river streamflow under different representative concentration pathways.

Climate change and excessive greenhouse gas emissions profoundly impact hydrological cycles, particularly in arid and semi-arid regions, necessitating assessments of their effects on water resource management, agriculture, soil fertility, nutrient transport, hydropower generation, and flood risk. This study investigates climate change repercussions on streamflow in the Zarrineh River Basin, Iran, across three decadal intervals (2020-2029, 2055-2064, and 2090-2099) aiming to develop effective adaptation and mitigation strategies. Four General Circulation Models (GCMs), chosen based on distinct Representative Concentration Pathways (RCPs) determined by the annual mean temperature gradient, are employed. These models generate daily maximum (Tmax) and minimum (Tmin) temperatures along with precipitation data. Subsequently, these variables are integrated into the Soil and Water Assessment Tool (SWAT) model to analyze river flow alterations for each decadal timeframe. Comparison between future projections and observed climate data reveals a gradual decline in precipitation and Tmax, coupled with a substantial increase in Tmin. The average precipitation diminishes from 0.77 mm in the period 1985-1994 to a range of 0.42-0.28 mm in 2090-2099. The simulated flow at the basin outlet highlights that the GCM with the highest annual mean temperature gradient yields the lowest streamflow, while conversely, the model with the lowest gradient generates the highest. Consequently, streamflow experiences a decline from 52 m3/s in 1985-1994 to a range of 41-20 m3/s in 2090-2099.

Mini-MEndR: a miniaturized 96-well predictive assay to evaluate muscle stem cell-mediated repair.

Background: Functional evaluation of molecules that are predicted to promote stem cell mediated endogenous repair often requires in vivo transplant studies that are low throughput and hinder the rate of discovery. To offer greater throughput for functional validation studies, we miniaturized, simplified and expanded the functionality of a previously developed muscle endogenous repair (MEndR) in vitro assay that was shown to capture significant events of in vivo muscle endogenous repair. Methods: The mini-MEndR assay consists of miniaturized cellulose scaffolds designed to fit in 96-well plates, the pores of which are infiltrated with human myoblasts encapsulated in a fibrin-based hydrogel to form engineered skeletal muscle tissues. Pre-adsorbing thrombin to the cellulose scaffolds facilitates in situ tissue polymerization, a critical modification that enables new users to rapidly acquire assay expertise. Following the generation of the 3D myotube template, muscle stem cells (MuSCs), enriched from digested mouse skeletal muscle tissue using an improved magnetic-activated cell sorting protocol, are engrafted within the engineered template. Murine MuSCs are fluorescently labeled, enabling co-evaluation of human and mouse Pax7+ cell responses to drug treatments. A regenerative milieu is introduced by injuring the muscle tissue with a myotoxin to initiate endogenous repair "in a dish". Phenotypic data is collected at endpoints with a high-content imaging system and is analyzed using ImageJ-based image analysis pipelines. Results: The miniaturized format and modified manufacturing protocol cuts reagent costs in half and hands-on seeding time ~ threefold, while the image analysis pipelines save 40 h of labour. By evaluating multiple commercially available human primary myoblast lines in 2D and 3D culture, we establish quality assurance metrics for cell line selection that standardizes myotube template quality. In vivo outcomes (enhanced muscle production and Pax7+ cell expansion) to a known modulator of MuSC mediated repair (p38/ß MAPK inhibition) are recapitulated in the miniaturized culture assay, but only in the presence of stem cells and the regenerative milieu. Discussion: The miniaturized predictive assay offers a simple, scaled platform to co-investigate human and mouse skeletal muscle endogenous repair molecular modulators, and thus is a promising strategy to accelerate the muscle endogenous repair discovery pipeline. Supplementary Information: The online version contains supplementary material available at 10.1186/s44330-024-00005-4.

Finite Element Analysis for Degenerative Cervical Myelopathy: Scoping Review of the Current Findings and Design Approaches, Including Recommendations on the Choice of Material Properties.

BACKGROUND: Degenerative cervical myelopathy (DCM) is a slow-motion spinal cord injury caused via chronic mechanical loading by spinal degenerative changes. A range of different degenerative changes can occur. Finite element analysis (FEA) can predict the distribution of mechanical stress and strain on the spinal cord to help understand the implications of any mechanical loading. One of the critical assumptions for FEA is the behavior of each anatomical element under loading (ie, its material properties). OBJECTIVE: This scoping review aims to undertake a structured process to select the most appropriate material properties for use in DCM FEA. In doing so, it also provides an overview of existing modeling approaches in spinal cord disease and clinical insights into DCM. METHODS: We conducted a scoping review using qualitative synthesis. Observational studies that discussed the use of FEA models involving the spinal cord in either health or disease (including DCM) were eligible for inclusion in the review. We followed the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. The MEDLINE and Embase databases were searched to September 1, 2021. This was supplemented with citation searching to retrieve the literature used to define material properties. Duplicate title and abstract screening and data extraction were performed. The quality of evidence was appraised using the quality assessment tool we developed, adapted from the Newcastle-Ottawa Scale, and shortlisted with respect to DCM material properties, with a final recommendation provided. A qualitative synthesis of the literature is presented according to the Synthesis Without Meta-Analysis reporting guidelines. RESULTS: A total of 60 papers were included: 41 (68%) "FEA articles" and 19 (32%) "source articles." Most FEA articles (33/41, 80%) modeled the gray matter and white matter separately, with models typically based on tabulated data or, less frequently, a hyperelastic Ogden variant or linear elastic function. Of the 19 source articles, 14 (74%) were identified as describing the material properties of the spinal cord, of which 3 (21%) were considered most relevant to DCM. Of the 41 FEA articles, 15 (37%) focused on DCM, of which 9 (60%) focused on ossification of the posterior longitudinal ligament. Our aggregated results of DCM FEA indicate that spinal cord loading is influenced by the pattern of degenerative changes, with decompression alone (eg, laminectomy) sufficient to address this as opposed to decompression combined with other procedures (eg, laminectomy and fusion). CONCLUSIONS: FEA is a promising technique for exploring the pathobiology of DCM and informing clinical care. This review describes a structured approach to help future investigators deploy FEA for DCM. However, there are limitations to these recommendations and wider uncertainties. It is likely that these will need to be overcome to support the clinical translation of FEA to DCM.

An intelligent decision support system for groundwater supply management and electromechanical infrastructure controls.

This study presents an intelligent Decision Support System (DSS) aimed at bridging the theoretical-practical gap in groundwater management. The ongoing demand for sophisticated systems capable of interpreting extensive data to inform sustainable groundwater decision-making underscores the critical nature of this research. To meet this challenge, telemetry data from six randomly selected wells were used to establish a comprehensive database of groundwater pumping parameters, including flow rate, pressure, and current intensity. Statistical analysis of these parameters led to the determination of threshold values for critical factors such as water pressure and electrical current. Additionally, a soft sensor was developed using a Random Forest (RF) machine learning algorithm, enabling real-time forecasting of key variables. This was achieved by continuously comparing live telemetry data to pump design specifications and results from regular field testing. The proposed machine learning model ensures robust empirical monitoring of well and pump health. Furthermore, expert operational knowledge from water management professionals, gathered through a Classical Delphi (CD) technique, was seamlessly integrated. This collective expertise culminated in a data-driven framework for sustainable groundwater facilities monitoring. In conclusion, this innovative DSS not only addresses the theory-application gap but also leverages the power of data analytics and expert knowledge to provide high-precision online insights, thereby optimizing groundwater management practices.

The significance of metabolic disease in degenerative cervical myelopathy: a systematic review.

Introduction: Degenerative cervical myelopathy (DCM) is a form of chronic spinal cord injury, with a natural history of potential for progression over time. Whilst driven by mechanical stress on the spinal cord from degenerative and congenital pathology, the neurological phenotype of DCM is likely to be modified by multiple systemic factors. The role of metabolic factors is therefore of interest, particularly given that ischaemia is considered a key pathological mechanism of spinal cord injury. The objective was therefore to synthesise current evidence on the effect of metabolism on DCM susceptibility, severity, and surgical outcomes. Methods: A systematic review in MEDLINE and Embase was conducted following PRISMA guidelines. Full-text papers in English, with a focus on DCM and metabolism, including diabetes, cardiovascular disease, anaemia, and lipid profile, were eligible for inclusion. Risk of methodological bias was assessed using the Joanna Briggs Institute (JBI) critical assessment tools. Quality assessments were performed using the GRADE assessment tool. Patient demographics, metabolic factors and the relationships between metabolism and spinal cord disease, spinal column disease and post-operative outcomes were assessed. Results: In total, 8,523 papers were identified, of which 57 met criteria for inclusion in the final analysis. A total of 91% (52/57) of included papers assessed the effects of diabetes in relation to DCM, of which 85% (44/52) reported an association with poor surgical outcomes; 42% of papers (24/57) discussed the association between cardiovascular health and DCM, of which 88% (21/24) reported a significant association. Overall, DCM patients with diabetes or cardiovascular disease experienced greater perioperative morbidity and poorer neurological recovery. They were also more likely to have comorbidities such as obesity and hyperlipidaemia. Conclusion: Metabolic factors appear to be associated with surgical outcomes in DCM. However, evidence for a more specific role in DCM susceptibility and severity is uncertain. The pathophysiology and natural history of DCM are critical research priorities; the role of metabolism is therefore a key area for future research focus. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42021268814.

Brain MRI changes in degenerative cervical myelopathy: a systematic review.

BACKGROUND: Degenerative cervical myelopathy (DCM) is the most common cause of adult spinal cord dysfunction globally. Associated neurological symptoms and signs have historically been explained by pathobiology within the cervical spine. However, recent advances in imaging have shed light on numerous brain changes in patients with DCM, and it is hypothesised that these changes contribute to DCM pathogenesis. The aetiology, significance, and distribution of these supraspinal changes is currently unknown. The objective was therefore to synthesise all current evidence on brain changes in DCM. METHODS: A systematic review was performed. Cross-sectional and longitudinal studies with magnetic resonance imaging on a cohort of patients with DCM were eligible. PRISMA guidelines were followed. MEDLINE and Embase were searched to 28th August 2023. Duplicate title/abstract screening, data extraction and risk of bias assessments were conducted. A qualitative synthesis of the literature is presented as per the Synthesis Without Meta-Analysis (SWiM) reporting guideline. The review was registered with PROSPERO (ID: CRD42022298538). FINDINGS: Of the 2014 studies that were screened, 47 studies were identified that used MRI to investigate brain changes in DCM. In total, 1500 patients with DCM were included in the synthesis, with a mean age of 53 years. Brain alterations on MRI were associated with DCM both before and after surgery, particularly within the sensorimotor network, visual network, default mode network, thalamus and cerebellum. Associations were commonly reported between brain MRI alterations and clinical measures, particularly the Japanese orthopaedic association (JOA) score. Risk of bias of included studies was low to moderate. INTERPRETATION: The rapidly expanding literature provides mounting evidence for brain changes in DCM. We have identified key structures and pathways that are altered, although there remains uncertainty regarding the directionality and clinical significance of these changes. Future studies with greater sample sizes, more detailed phenotyping and longer follow-up are now needed. FUNDING: ODM is supported by an Academic Clinical Fellowship at the University of Cambridge. BMD is supported by an NIHR Clinical Doctoral Fellowship at the University of Cambridge (NIHR300696). VFJN is supported by an NIHR Rosetrees Trust Advanced Fellowship (NIHR302544). This project was supported by an award from the Rosetrees Foundation with the Storygate Trust (A2844).

The impact of phosphodiesterase inhibition on neurobehavioral outcomes in preclinical models of traumatic and non-traumatic spinal cord injury: a systematic review.

Study design: Systematic review. Objective: The objective of this study was to evaluate the impact of phosphodiesterase (PDE) inhibitors on neurobehavioral outcomes in preclinical models of traumatic and non-traumatic spinal cord injury (SCI). Methods: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and was registered with PROSPERO (CRD42019150639). Searches were performed in MEDLINE and Embase. Studies were included if they evaluated the impact of PDE inhibitors on neurobehavioral outcomes in preclinical models of traumatic or non-traumatic SCI. Data were extracted from relevant studies, including sample characteristics, injury model, and neurobehavioral assessment and outcomes. Risk of bias was assessed using the SYRCLE checklist. Results: The search yielded a total of 1,679 studies, of which 22 met inclusion criteria. Sample sizes ranged from 11 to 144 animals. PDE inhibitors used include rolipram (n = 16), cilostazol (n = 4), roflumilast (n = 1), and PDE4-I (n = 1). The injury models used were traumatic SCI (n = 18), spinal cord ischemia (n = 3), and degenerative cervical myelopathy (n = 1). The most commonly assessed outcome measures were Basso, Beattie, Bresnahan (BBB) locomotor score (n = 13), and grid walking (n = 7). Of the 22 papers that met the final inclusion criteria, 12 showed a significant improvement in neurobehavioral outcomes following the use of PDE inhibitors, four papers had mixed findings and six found PDE inhibitors to be ineffective in improving neurobehavioral recovery following an SCI. Notably, these findings were broadly consistent across different PDE inhibitors and spinal cord injury models. Conclusion: In preclinical models of traumatic and non-traumatic SCI, the administration of PDE inhibitors appeared to be associated with statistically significant improvements in neurobehavioral outcomes in a majority of included studies. However, the evidence was inconsistent with a high risk of bias. This review provides a foundation to aid the interpretation of subsequent clinical trials of PDE inhibitors in spinal cord injury. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=150639, identifier: CRD42019150639.

Novel paraneoplastic mechanism for cerebellar ataxia in Erdheim-Chester disease.

We report a case of BRAF-mutation positive Erdheim-Chester disease presenting with a cerebellar ataxia. This is the first such case to be reported without structural MRI abnormalities but with a single intrathecally produced oligoclonal band. Now that the histiocytoses have been recharacterised as neoplastic, we speculate that the mechanism of the ataxia in our case is paraneoplastic. We highlight the importance of searching for BRAF mutations in this disease, as their presence leads to effective personalised treatments.

Combination of pricing and inventory policies for deteriorating products with sustainability considerations.

Economic, environmental, and social criteria are all being taken into consideration simultaneously when determining pricing policies or inventory levels in sustainable production management. The combination of pricing and inventory policies is an important source of leverage for the efficient management of perishable products. This paper, among the first studies, proposes the problem of devising optimal pricing and inventory management decisions simultaneously where the environmental and social criteria are contributed for perishable complementary products replenished and sold by the same company. This study considers two interrelated price-sensitive linear demand functions to consider the possibility of shortage with both budget and warehouse capacity constraints. Another contribution of the proposed model is to consider an upper bound for environmental pollution and a lower bound for job opportunities as the constraints to the model. As a complex optimization model, the challenge of complexity is addressed by a heuristic algorithm for finding an optimal solution. After an extensive analysis using numerical examples, some managerial insights are concluded from the results. One finding from these analyses confirms that the total capacity of the warehouse, the total available budget, carbon emissions, and variable job opportunities have a high impact on the optimal solution to find a balance between sustainability criteria for making pricing and inventory policies.

Acute quadriplegia and death following a routine MRI for undiagnosed degenerative cervical myelopathy.

Bilateral upper limb paraesthesia and pain are common symptoms of degenerative cervical myelopathy (DCM). Such symptoms instigate investigation by cervical spine magnetic resonance imaging (MRI). This was the case for our patient, who was 72-years-in age and otherwise fit and well. During the scan he unfortunately developed sudden onset quadriplegia secondary to an intervertebral disc prolapse. This necessitated intubation due to respiratory failure and urgent transfer to the neurosciences critical care unit at a tertiary neurosciences centre. Despite prompt surgical decompression, he did not regain function. Extubation was unsuccessful on three occasions. Following discussion between the patient and his family, ventilation was withdrawn, and he died the following day. This case highlights the potentially devastating consequences of DCM and poses questions about the aetiology of DCM.

Application and planning of an energy-oriented stochastic disassembly line balancing problem.

End-of-life (EOL) products are getting more and more attention as a result of the rapid decline in environmental resources and the dramatic rise in population at the moment. Disassembly is a crucial step in the reuse of EOL products. However, the disassembly process for EOL products is highly uncertain, and the disassembly planning method may not produce the anticipated outcomes in actual implementation. Based on the physical nature of the product disassembly process with multiple uncertain variables, certainty disassembly cannot adequately characterize the uncertain variables effectively. Uncertainty disassembly takes into account the changes in parts caused by product use, such as wear and corrosion, which can better coordinate the arrangement of disassembly tasks and better match the actual remanufacturing process. After analysis, it was found that most of studies on uncertain disassembly focus on the economic efficiency perspective and lack of energy consumption considerations. For the gaps in the current study, this paper proposes a stochastic energy consumption disassembly line balance problem (SEDLBP) and constructs a mathematical model of SEDLBP based on the disassembly of spatial interference matrix, In this model, the energy consumption generated by the disassembly operation and workstation standby is not a constant value but is generated stochastically in a uniformly distributed interval. In addition, an improved social engineering optimization algorithm that incorporates stochastic simulation (SSEO) is proposed in this paper to effectively address the issue. The incorporation of swap operators and swap sequences in SSEO makes it possible to solve discrete optimization problems efficiently. A comparison of a case study with some well-tested intelligent algorithms demonstrates the efficacy of the solutions produced by the proposed SSEO.

A survey of multi-criteria decision-making techniques for green logistics and low-carbon transportation systems.

With the increasing severity of environmental problems, low-carbon development has become an inevitable choice. Nowadays, low-carbon green sustainable development is influenced by a variety of factors such as social, environmental, technological, and economic development levels, making its development complex, which in turn imposes challenges on decision-makers. In this context, the application of multi-criteria decision-making (MCDM) in different areas of sustainable development engineering has become a hot topic. Although many reviews of MCDM techniques already exist, there is a lack of holistic review efforts on MCDM in the field of low-carbon transport and green logistics. Considering these shortcomings in the state of the art, this paper systematically reviews more than 190 papers from 2010 to 2022, constructs a general structure of MCDM techniques for this research topic, provides a comprehensive review and analysis of it, and clarifies the current practices. Furthermore, future directions for the development of MCDM techniques for green logistics and low-carbon transportation systems are presented as well.

Wildlife resource conservation and utilization for achieving sustainable development in China: main barriers and problem identification.

The rapid growth of the industrial economy has affected the survival of wildlife, and the decline in wildlife resources will in turn have some negative impact on the industrial economy. For the sustainable development of the industrial economy, human beings began to reflect on traditional development thinking and strive to find a development strategy that harmonizes industrial economic development and resource protection, and wildlife protection gradually attracted people's attention. "Protecting wild animals, maintaining ecological balance, and promoting economic development" has become a hot topic in the new century. Wildlife resources are valuable natural resources and play an important role in the ecosystem, which is related to the well-being and future of human beings. In recent years, China has made great progress in wildlife protection, while protecting and expanding wildlife habitats, introducing relevant laws and regulations, and other measures which have been implemented recently. However, there are still shortcomings in the protection of wildlife in China. Over-utilization, habitat loss and degradation, environmental pollution, climate change, weak legal awareness, and indiscriminate hunting all pose serious threats to wildlife in China. In this regard, this paper summarizes the main problems and barriers to wildlife resource conservation and utilization in China. Based on the analytic hierarchy process (AHP), the main technology factors influencing wildlife resource conservation and utilization in China are identified. Finally, the future research development direction of wildlife conservation is discussed based on the critical factors. This can provide some guidance for developing wildlife resource conservation and utilization for a sustainable ecosystem in China.

Hybrid evolutionary algorithm for stochastic multiobjective disassembly line balancing problem in remanufacturing.

With the development of the industrial economy and the accelerated renewal of products, many end-of-life products (EOL) have been generated to pollute our environment. This fact highlights the importance of recycling and remanufacturing EOL products as an active research topic. An efficient disassembly line is one solution for improving the remanufacturing and recycling processes of EOL products while reducing the environmental pollution. Although many optimization models and intelligent algorithms were developed to address the disassembly line balancing problem (DLBP), uncertainty was ignored by them. To alleviate the drawbacks of uncertainty for the disassembly operation, this study proposes a stochastic multi-objective optimization model for the DLBP minimizing the disassembly idle rate, smoothness, and energy consumption generated during the operation under uncertain operation time. Another novelty of this paper is to present an improved version of the northern goshawk optimization algorithm using a stochastic simulation method to solve the proposed model. The feasibility of the proposed model and the applicability of the developed algorithm are shown by two extensive examples. Finally, the performance of the proposed algorithm is revealed by a comparison with recent and state-of-the-art algorithms from the literature.

Meeting the Shared Goals of a Student-Selected Component: Pilot Evaluation of a Collaborative Systematic Review.

BACKGROUND: Research methodology is insufficiently featured in undergraduate medical curricula. Student-selected components are designed to offer some research opportunities but frequently fail to meet student or supervisor expectations, such as completion or publication. We hypothesized that a collaborative, educational approach to a systematic review (SR), whereby medical students worked together, may improve student experience and increase success. OBJECTIVE: This study aimed to establish whether offering a small team of students the opportunity to take part in the screening phase of SRs led by an experienced postgraduate team could enhance the learning experience of students, overcome the barriers to successful research engagement, and deliver published output. METHODS: Postgraduate researchers from the University of Cambridge led a team of 14 medical students to work on 2 neurosurgical SRs. One student was appointed as the lead for each SR. All students were provided with training on SR methodology and participated in title and abstract screening using Rayyan software. Students completed prepilot, midscreening, and postscreening questionnaires on their research background, perceptions, knowledge, confidence, and experience. Questions were scored on a Likert scale of 1 (strongly disagree) to 10 (strongly agree). RESULTS: Of the 14 students involved, 29% (n=4) reported that they had received sufficient training in research methodology at medical school. Positive trends in student knowledge, confidence, and experience of SR methodology were noted across the 3 questionnaire time points. Mean responses to "I am satisfied with the level of guidance I am receiving," "I am enjoying being involved in the SR process," and "I could not gain this understanding of research from passive learning e.g., textbook or lecture" were greater than 8.0 at all time points. Students reported "being involved in this research has made me more likely to do research in the future" (mean 8.57, SD 1.50) and that "this collaborative SR improved my research experience" (mean 8.50, SD 1.56). CONCLUSIONS: This collaborative approach appears to be a potentially useful method of providing students with research experience; however, it requires further evaluation.

Analysis of Incidence and Reasons for Re-intervention After Aortic Valve Replacement Using the Trifecta Aortic Bioprosthesis.

Trifecta bioprosthesis claims favorable hemodynamic performance. However, reports of structural valve deterioration (SVD) raise concerns of its long-term durability. We assessed outcomes with the Trifecta valve over a 10-year period. All patients receiving Trifecta bioprostheses between October 2011 and October 2020 were included. Perioperative and survival characteristics were prospectively collated in an independent database. Re-intervention was recorded as a surrogate for SVD. Nine hundred and forty-four patients (mean age 72.82 years ± 8.13, 58% male) underwent aortic valve replacement with the Trifecta valve. At 10-years, 1.4% of patients required a redo operation, giving an overall freedom from re-intervention of 98.6%. The mean time to re-intervention was 48.87 months. Survival was 73.58% and 76.92% in patients who did not require re-intervention vs re-intervention group, respectively. In a large, single-center cohort, the Trifecta aortic bioprosthesis had a 1.4% all-cause re-intervention rate at 10-years, with insignificant impact on survival.

Effect of eight weeks respiratory muscle training on respiratory capacity, functional capacity and quality of life on subjects with mild to moderate relapsing-remitting multiple sclerosis: A single-blinded randomized controlled trial.

BACKGROUND: Multiple Sclerosis (MS) is a chronic inflammatory disease of the nervous system leading to muscle weakness, including the respiratory muscles that cause pulmonary complications, impair functional capacity, increased fatigue, and as a result decreases the quality of life. AIM: The purpose of the present study is to examine the influence of 8 weeks of respiratory muscle training (RMT) on pulmonary function and respiratory muscle strength in MS patients. METHODS: The present study was a single-blind, randomized controlled trial that was conducted on 36 (27 Female, 9 Male) relapsing-remitting MS patients who were definitively diagnosed by a neurologist and randomly were divided into intervention and control groups. Both groups were educated on lifestyle modification with an emphasis on regular physical activity. In addition, the intervention group was prescribed eight weeks of respiratory muscle training with a threshold resistance device, daily, twice a day for three sets of 15 repetitions per set. Maximal expiratory pressure (PImax), maximal expiratory pressure (PEmax), spirometric indices, functional tests (six-minute walk test, timed up and go test), fatigue questionnaire, and questionnaire of quality of life were assessed before and after trials. RESULTS: A total of 36 patients (75% female; mean age 38.00(8.86) years; BMI 26.56(2.64) kg/m2) were included in the study. The strength of inspiratory and expiratory muscles, respiratory function, fatigue, and quality of life were significantly improved in the intervention group (p<0.005). In addition, there was a significant improvement in the rate of fatigue and quality of life in all their dimensions (p<0.005). Only in the six-minute walk test, no significant improvement was seen in the intervention group compared to the control group (p = 0.262). CONCLUSION: Findings could help therapists to provide MS patients with more effective respiratory muscle training protocols to maximize the benefits of rehabilitation.

The Effect of miR-106b-5p Expression in The Production of iPS-Like Cells from Mice SSCs during The Formation of Teratoma and The Three Embryonic Layers.

Objective: According to the mounting data, microRNAs (miRNAs) may play a key role in reprogramming. miR-106b
is considered as an enhancer in reprogramming efficiency. Based on induced pluripotent stem cells (iPSCs), cell treatments have a huge amount of potential. One of the main concerns about using iPSCs in therapeutic settings is the possibility of tumor formation. It is hypothesized that a procedure that can reprogram cells with less genetic manipulation reduces the possibility of tumorigenicity.
Materials and Methods: In this experimental study, miR-106b-5p transduced by pLV-miRNA vector into mice isolated spermatogonial stem cells (SSCs) to achieve iPS-like cells. Then the transduced cells were cultured in specific conditions to study the formation of three germ layers. The tumorigenicity of these iPS-like cells was investigated by transplantation into male BALB/C mice.
Results: We show that SSCs can be successfully reprogrammed into induced iPS-like cells by pLV-miRNA vector to transduce the hsa-mir-106b-5p into SSCs and generating osteogenic, neural and hepatoblast lineage cells in vitro as a result of pluripotency. Although these iPS-like cells are pluripotent, they cannot form palpable tumors in vivo.
Conclusion: These results demonstrate that infection of hsa-mir-106b-5p into SSCs can reprogram them into iPSCs
and advanced germ cell lineages without tumorigenicity. Also, a novel approach for studying the generation of iPSCs
and the application of iPS or iPS-like cells in regenerative medicine is presented.

MiR-106b-5p Regulates the Reprogramming of Spermatogonial Stem Cells into iPSC (Induced Pluripotent Stem Cell)-Like Cells

Background: Recent years have brought notable progress in raising the efficiency of the reprogramming technique so that approaches have evolved from known transgenic factors to only a few miRNAs. Nevertheless, there is a poor understanding of both the key factors and biological networks underlying this reprogramming. The present study aimed to investigate the potential of miR-106b-5p in regulating spermatogonial stem cells (SSCs) to induced pluripotent stem cell (iPSC)-like cells. Methods: We used SSCs because pluripotency is inducible in SSCs under defined culture conditions, and they have a few issues compared to other adult stem cells. As both signaling and post-transcriptional gene controls are critical for pluripotency regulation, we traced the expression of Oct-4, Sox-2, Klf-4, c-Myc, and Nanog (OSKMN). Besides, we considered miR-106b-5p targets using bioinformatic methods. Results: Our results showed that transfected SSCs with miR-106b-5p increased the expression of the OSKMN factors, which was significantly more than negative control groups. Moreover, using the functional miRNA enrichment analysis, online tools, and databases, we predicted that miR-106b-5p targeted a signaling pathway gene named MAPK1/ERK2, related to regulating stem cell pluripotency. Conclusion: Together, our data suggest that miR-106b-5p regulates the reprogramming of SSCs into iPSC-like cells. Furthermore, noteworthy progress in the in vitro development of SSCs indicates promise reservoirs and opportunities for future clinical trials.

Effect of endurance training on cardiopulmonary fitness in people with multiple sclerosis.

INTRODUCTION: Disturbances associated with Multiple Sclerosis (MS) can be due to the pathologic process of the disease or insufficient physical fitness. The benefits of exercise in improving cardiopulmonary fitness have been demonstrated in animal studies and also clinical trials on cardiovascular patients and healthy human cases; however, its effectiveness in people with MS(pwMS) is still unknown. people with MS often engage in rehabilitation programs for exercise tolerance improvement. Therefore, it is necessary to investigate the effect of this specific intervention on cardiopulmonary fitness of these patients. The present study intended to illustrate the etiology of exercise intolerance in pwMS and also the effects of exercise on these etiological factors. METHODS AND RESULTS: The present interventional study included 21 female patients suffering from Relapsing-Remitting MS (RR-MS) who had a mean age of 35 ± 5.18 years and the Expanded Disability Status Scale (EDSS) scores of 1 to 4. All the participants underwent Cardiopulmonary Exercise Testing (CPET) on an ergometer pre- and post-intervention. The intervention included 18 sessions of endurance training using a stationary bicycle with an intensity of 70% of the peak Heart Rate (HR) or 60% of the peak VO2 (Volume of oxygen consumption) under the supervision and cardiac monitoring. A total of 24 variables, including the parameters cardiopulmonary fitness (aerobic fitness), were investigated. Also, all the maximal variables were analyzed in the same RER(Respiratory Exchange Ration) (a mean RER of 0.92) pre- and post-intervention. According to the results, a total of 17 variables out of 24 study variables had significant changes (P < 0.05). CONCLUSION: The present study showed that even a short, 6-week course of aerobic exercise could change the peak HR and VO2, improving the cardio pulmonary fitness in these patients. This indicates the adaptation of the cardiopulmonary system to exercise in pwMS. In other words, these cardiopulmonary fitness variables improvement due to exercise demonstrates that this pathology is not merely caused by the MS-induced Central Nervous System (CNS) involvement and can be improved by improving cardiopulmonary fitness.