Search results for: therapeutic results

Authors: Jessica Chorostecki, Aashka Shah, Fen Bao, Ginny Bao, Edwin George, Navid Seraji-Bozorgzad, Veronica Gorden, Christina Caon, Elliot Frohman

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Background: Parkinson’s Disease (PD) is a neuro degenerative disorder associated with the loss of dopaminergic cells and the presence α-synuclein (AS) aggregation in of Lewy bodies. Both dopaminergic cells and AS are found in the retina. Optical coherence tomography (OCT) allows high-resolution in-vivo examination of retinal structure injury in neuro degenerative disorders including PD. Methods: We performed a cross-section OCT study in patients with definite PD and healthy controls (HC) using Spectral Domain SD-OCT platform to measure the peripapillary retinal nerve fiber layer (pRNFL) thickness and total macular volume (TMV). We performed intra-retinal segmentation with fully automated segmentation software to measure the volume of the RNFL, ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), and the outer nuclear layer (ONL). Segmentation was performed blinded to the clinical status of the study participants. Results: 101 eyes from 52 PD patients (mean age 65.8 years) and 46 eyes from 24 HC subjects (mean age 64.1 years) were included in the study. The mean pRNFL thickness was not significantly different (96.95 μm vs 94.42 μm, p=0.07) but the TMV was significantly lower in PD compared to HC (8.33 mm3 vs 8.58 mm3 p=0.0002). Intra-retinal segmentation showed no significant difference in the RNFL volume between the PD and HC groups (0.95 mm3 vs 0.92 mm3 p=0.454). However, GCL, IPL, INL, and ONL volumes were significantly reduced in PD compared to HC. In contrast, the volume of OPL was significantly increased in PD compared to HC. Conclusions: Our finding of the enlarged OPL corresponds with mRNA expression studies showing localization of AS in the OPL across vertebrate species and autopsy studies demonstrating AS aggregation in the deeper layers of retina in PD. We propose that the enlargement of the OPL may represent a potential biomarker of AS aggregation in PD. Longitudinal studies in larger cohorts are warranted to confirm our observations that may have significant implications in disease monitoring and therapeutic development.

Keywords: Optical Coherence Tomography, biomarker, Parkinson's disease, alpha-synuclein, retina

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Authors: Nizar Chaira

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Dates, main products of the oases, due to their therapeutic interests, are considered highly nutritious fruit. Several studies on the valuation biotechnology and technology of dates are made, and several products are already prepared. Isolation of the yeast Saccharomyces cerevisiae, naturally presents in a scrap of date, optimization of growth in the medium based on date syrup and production biomass can potentially expand the range of secondary products of dates. To this end, this paper tries to study the suitability for processing dates technology and biotechnology to use the date pulp as a carbon source for biological transformation. Two strains of Saccharomyces cerevisiae isolated from date syrup (S1, S2) and a commercial strain have used for this study. After optimization of culture conditions, production in a fermenter on two different media (date syrup and beet molasses) was performed. This is followed by studying the kinetics of growth, protein production and consumption of sugars in crops strain 1, 2 and the commercial strain and on both media. The results obtained showed that a concentration of 2% sugar, 2.5 g/l yeast extract, pH 4.5 and a temperature between 25 and 35°C are the optimal conditions for cultivation in a bioreactor. The exponential phase of the specific growth rate of a strain on both media showed that it is about 0.3625 h-1 for the production of a medium based on date syrup and 0.3521 h-1 on beet molasses with a generation time equal to 1.912 h and on the medium based on date syrup, yeast consumes preferentially the reducing sugars. For the production of protein, we showed that this latter presents an exponential phase when the medium starts to run out of reducing sugars. For strain 2, the specific growth rate is about 0.261h-1 for the production on a medium based on date syrup and 0207 h-1 on beet molasses and the base medium syrup date of the yeast consumes preferentially reducing sugars. For the invertase and other metabolits, these increases rapidly after exhaustion of reducing sugars. The comparison of productivity between the three strains on the medium based on date syrup showed that the maximum value is obtained with the second strain: p = 1072 g/l/h as it is about of 0923 g/l/h for strain 1 and 0644 g/l/h for the commercial strain. Thus, isolates of date syrup are more competitive than the commercial strain and can give the same performance in a shorter time with energy gain.

Keywords: date palm, fermentation, molasses, Saccharomyces, syrup

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Authors: Lourdes Hanna, Edward Poluyi, Chibuikem Ikwuegbuenyi, Eghosa Morgan, Grace Imaguezegie

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Background: Degeneration of the central nervous system (CNS), also known as neurodegeneration, describes an age-associated progressive loss of the structure and function of neuronal materials, leading to functional and mental impairments. Main body: Neuroinflammation contributes to the continuous worsening of neurodegenerative states which are characterised by functional and mental impairments due to the progressive loss of the structure and function of neu-ronal materials. Some of the most common neurodegenerative diseases include Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS). Whilst neuroinflammation is a key contributor to the progression of such disease states, it is not the single cause as there are multiple factors which contribute. Theoretically, non-steroidal anti-inflammatory drugs (NSAIDs) have potential to target neuroinflammation to reduce the severity of disease states. Whilst some animal models investigating the effects of NSAIDs on the risk of neurodegenerative diseases have shown a beneficial effect, this is not the same finding. Conclusion: Further investigation using more advanced research methods is required to better understand neuroinflammatory pathways and understand if there is still a potential window for NSAID efficacy.

Keywords: intervention, central nervous system, neurodegeneration, neuroinflammation

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Authors: Ipsita Pujari, Abitha Thomas, Vidhu S. Babu, K. Satyamoorthy

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Orchids are esteemed as celebrities in cut flower industry globally, due to their long-lasting fragrance and freshness. Apart from splendor, the unique metabolites endowed with pharmaceutical potency have made them one of the most hunted in plant kingdom. This had led to their trafficking, resulting in habitat loss, subsequently making them occupiers of IUCN red list as RET species. Many of the orchids especially wild varieties still remain undiscovered. In view to protect and conserve the wild germplasm, researchers have been inventing novel micropropagation protocols; thereby conserving Orchids. India is overflowing with exclusive wild cultivars of Orchids, whose pharmaceutical properties remain untapped and are not marketed owing to relatively small flowers. However, their germplasm is quite pertinent to be preserved for making unusual hybrids. Dendrobium genus is the second largest among Orchids exists in India and has highest demand attributable to enduring cut flowers and significant therapeutic uses in traditional medicinal system. Though the genus is quite endemic in Western Ghat regions of the country, many species are still anonymous with their unknown curative properties. A standard breeding cycle in Orchids usually takes five to seven years (Dendrobium hybrids taking a long juvenile phase of two to five years reaching maturity and flowering stage) and this extensive life cycle has always hindered the development of Dendrobium breeding. Dendrobium is reported with essential therapeutic plant bio-chemicals and ‘Moscatilin’ is one, found exclusive to this famous Dendrobium genus. Moscatilin is reported to have anti-mutagenic and anti-cancer properties, whose positive action has very recently been demonstrated against a range of cancers. Our preliminary study here established a simple and economic small-scale propagation protocol of Dendrobium ovatum describing in vitro production of Moscatilin. Subsequently for enhancing the content of Moscatilin, an efficient experimental related to the organization of transgenic (hairy) D. ovatum root cultures through infection of Agrobacterium rhizogenes 2364 strain on MS basal medium is being reported in the present study. Hairy roots generated on almost half of the explants used (spherules, in vitro plantlets and calli) maintained through suspension cultures, after 8 weeks of co-cultivation with Agrobacterium rhizogenes. GFP assay performed with isolated hairy roots has confirmed the integrative transformation which was further positively confirmed by PCR using rolB gene specific primers. Reverse phase-high performance liquid chromatography and mass spectrometry techniques were used for quantification and accurate identification of Moscatilin respectively from transgenic systems. A noticeable ~3 fold increase in contents were observed in transformed D. ovatum root cultures as compared to the simple in vitro culture, callus culture and callus regeneration plantlets. Role of elicitors e.g., Methyl jasmonate, Salicylic acid, Yeast extract and Chitosan were tested for elevating the Moscatilin content to obtain a comprehensive optimized protocol facilitating the in vitro production of valuable Moscatilin with larger yield. This study would provide evidence towards the in vitro assembly of Moscatilin within a short time-period through not a so-expensive technology for the first time. It also serves as an appropriate basis for bioreactor scale-up resulting in commercial bioproduction of Moscatilin.

Keywords: bioproduction, Dendrobium ovatum, hairy root culture, moscatilin

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Authors: Uvais Qidwai, Mohamed Shakir

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This paper presents an initial study related to the use of robotic toys as teaching and therapeutic aid tools for teachers and care-givers as well as parents of children with various levels of autism spectrum disorder (ASD). Some of the most common features related to the behavior of a child with ASD are his/her social isolation, living in their own world, not being physically active, and not willing to learn new things. While the teachers, parents, and all other related care-givers do their best to improve the condition of these kids, it is usually quite an uphill task. However, one remarkable observation that has been reported by several teachers dealing with ASD children is the fact that the same children do get attracted to toys with lights and sounds. Hence, this project targets the development/modifications of such existing toys into appropriate behavior training tools which the care-givers can use as they would desire. Initially, the remote control is in hand of the trainer, but after some time, the child is entrusted with the control of the robotic toy to test for the level of interest. It has been found during the course of this study that children with quite low learning activity got extremely interested in the robot and even advanced to controlling the robot with the Electromyography (EMG). It has been observed that the children did show some hesitation in the beginning 5 minutes of the very first sessions of such interaction but were very comfortable afterwards which has been considered as a very strong indicator of the potential of this technique in teaching and rehabilitation of children with ASD or similar brain disorders.

Keywords: Autism Spectrum Disorder (ASD), robotic toys, IR control, electromyography, LabVIEW based remote control

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Authors: Berrak Yildiz, Hinal Shah, Justine Fernandez, Nazje James, Anna Brown

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Cervical ectopic pregnancy, a rare type of ectopic pregnancies, is defined by blastocyst implantation within the cervical canal rather than the endometrium. Its rarity and potential for severe hemorrhage make cervical ectopic pregnancy a diagnostic and therapeutic challenge. A 39-year-old woman, G5P2022, with a history of two cesarean sections and two elective terminations, presented to the emergency department with vaginal bleeding and pelvic pain. Initial assessment showed a beta-hCG level of 2,853 mIU/mL, and transvaginal ultrasound revealed a small, irregular gestational sac at the level of the internal cervical os. Serial betahCG measurements over subsequent visits showed a declining trend, consistent with a nonviable pregnancy. The patient was ultimately treated with methotrexate at a dose of 50 mg/m² (total 100 mg), following which she reported no further symptoms. On follow-up, her beta-hCG level returned to the normal non-pregnant range, with no additional intervention needed. This case highlights the importance of early diagnosis in cervical ectopic pregnancy to avoid complications like hysterectomy. Methotrexate is an effective first-line treatment in hemodynamically stable patients, offering a conservative approach that can preserve fertility. The success in this patient underscores the role of prompt diagnosis and careful management in achieving resolution while minimizing invasive procedures.

Keywords: beta-hCG, cervical, ectopic, methotrexate

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Authors: Mohammed Al-Zubaidi, Katherine Ong, Pravin Viswambaram, Steve McCombie, Oliver Oey, Jeremy Ong, Richard Gauci, Ronny Low, Dickon Hayne

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Objective: Lymph node involvement along with distant metastasis in a patient with invasive bladder cancer determines the disease survival, therefeor, it is an essential determinant of the therapeutic management and outcome. This retrospective study aims to determine the accuracy of FDG PET scan in detecting lymphatic involvement and distant metastatic urothelial cancer compared to conventional CT staging. Method: A retrospective review of 76 patients with UC or BC who underwent surgery or confirmatory biopsy that was staged with both CT and 18F-FDG-PET (up to 8 weeks apart) between 2015 and 2020. Fifty-sevenpatients (75%) had formal pelvic LN dissection or biopsy of suspicious metastasis. 18F-FDG-PET reports for positive sites were qualitative depending on SUV Max. On the other hand, enlarged LN by RECIST criteria 1.1 (>10 mm) and other qualitative findings suggesting metastasis were considered positive in CT scan. Histopathological findings from surgical specimens or image-guided biopsies were considered the gold standard in comparison to imaging reports. 18F-FDG-avid or enlarged pelvic LNs with surgically proven nodal metastasis were considered true positives. Performance characteristics of 18F-FDG-PET and CT, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (PPV), were calculated. Results: Pelvic LN involvement was confirmed histologically in 10/57 (17.5%) patients. Sensitivity, specificity, PPV and NPV of CT for detecting pelvic LN metastases were 41.17% (95% CI:18-67%), 100% (95% CI:90-100%) 100% (95% CI:59-100%) and 78.26% (95% CI:64-89%) respectively. Sensitivity, specificity, PPV and NPV of 18F-FDG-PET for detecting pelvic LN metastases were 62.5% (95% CI:35-85%), 83.78% (95% CI:68-94%), 62.5% (95% CI:35-85%), and 83.78% (95% CI:68-94%) respectively. Pre-operative staging with 18F-FDG-PET identified the distant metastatic disease in 9/76 (11.8%) patients who were occult on CT. This retrospective study suggested that 18F-FDG-PET may be more sensitive than CT for detecting pelvic LN metastases. 7/76 (9.2%) patients avoided cystectomy due to 18F-FDG-PET diagnosed metastases that were not reported on CT. Conclusion: 18F-FDG-PET is more sensitive than CT for pelvic LN metastases, which can be used as the standard modality of bladder cancer staging, as it may change the treatment by detecting lymph node metastasis that was occult in CT. Further research involving randomised controlled trials comparing the diagnostic yield of 18F-FDG-PET and CT in detecting nodal and distant metastasis in UC or BC is warranted to confirm our findings.

Keywords: FDG PET, CT scan, urothelial cancer, bladder cancer

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Authors: Jake Hindmarch, Edward Farley, Norman Eizenberg, Mark Midwinter

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There is a need to bring the anatomical knowledge of medical students up to the standards required by surgical specialties. Contention exists amongst anatomists, clinicians, and surgeons about the standard of anatomical knowledge medical students need. The aim of this study was to explore the standards which the Royal Australasian College of Surgeons are applying knowledge of anatomy. Furthermore, to align medical school teaching to what the surgical profession requires from graduates.: The 2018 volume of the ANZ Journal of Surgery was narrowed down to 254 articles by applying the search term “Anatomy”. The main topic was then extracted from each paper. The content of the paper was assessed for ‘novel description’ or ‘application’ of anatomical knowledge’ and classified accordingly. The majority of papers with an anatomical focus was from the general surgery specialty, which focused on surgical techniques, outcomes and management. Vascular surgery had the highest percentage of papers with a novel description and application of anatomy. Cardiothoracic and paediatric surgery had no papers with a novel description of anatomy. Finally, a novel application of anatomy was the main focus of each speciality. Firstly, a high proportion of novel applications and descriptions of anatomy are in general surgery. Secondly, vascular surgery had the largest proportion of novel application and description of anatomy, namely due to the rise of therapeutic imaging and endovascular techniques. Finally, all disciplines demonstrated a trend towards having a higher proportion of novel application of anatomical knowledge

Keywords: anatomical knowledge, anatomy, surgery, novel anatomy

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Authors: Fateme Nokhodchi Bonab

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Studies related to magnetic resonance imaging (MRI) and drug delivery are reviewed in this study to demonstrate the role of transport theory in porous media in facilitating advances in biomedical applications. Diffusion processes are believed to be important in many therapeutic modalities such as: B. Delivery of drugs to the brain. We analyse the progress in the development of diffusion equations using the local volume average method and the evaluation of applications related to diffusion equations. Torsion and porosity have significant effects on diffusive transport. In this study, various relevant models of torsion are presented and mathematical modeling of drug release from biodegradable delivery systems is analysed. In this study, a new model of drug release kinetics from porous biodegradable polymeric microspheres under bulk and surface erosion of the polymer matrix is presented. Solute drug diffusion, drug dissolution from the solid phase, and polymer matrix erosion have been found to play a central role in controlling the overall drug release process. This work paves the way for MRI and drug delivery researchers to develop comprehensive models based on porous media theory that use fewer assumptions compared to other approaches.

Keywords: MRI, porous media, drug delivery, biomedical applications

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Authors: Samy Selim

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Natural products are still major sources of innovative therapeutic agents for various conditions, including infectious diseases. Peganum harmala L. oil had wide range uses as traditional medicinal plants. The current study was designed to evaluate the antibacterial activity of P. harmala essential oil. The chemical constitutes and toxicity of these oils was also determined to obtain further information on the correlation between the chemical contents and antibacterial activity. The antibacterial effect of the essential oils of P. harmala oil was studied against some foodborne pathogenic bacteria species. The oil of plant was subjected to gas chromatography-mass spectrometry (GC/MS). The impact of oils administration on the change in rate of weight gain and complete blood picture in hamsters were investigated. P. harmala oil had strong antibacterial effect against bacterial species especially at minimum inhibitory concentration (MIC) less than 75.0 μg/ml. From the oil of P. harmala, forty one compounds were identified, and the major constituent was 1-hexyl-2-nitrocyclohexane (9.07%). Acute toxicity test was performed on hamsters and showed complete survival after 14 days, and there were no toxicity symptoms occurred. This study demonstrated that these essential oils seemed to be destitute of toxic effect which could compromise the medicinal use of these plants in folk medicine.

Keywords: analysis mass spectrometry, antibacterial activities, acute toxicity, chemical constitutes, gas chromatography, weight gain, Peganum harmala

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Authors: Abiola Falilat Ibraheem, Akinyimika Sowunmi, Valerie Otti

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Background: Introduction of innovative cancer clinical trials to Nigeria is a critical step in addressing global inequities of cancer burden. Low health and clinical trial literacy among Nigerian patients have been sighted as a significant barrier to ensuring that patients enrolled in clinical trials are truly informed. Video intervention has been shown to be the most proactive method to improving patient’s clinical trial knowledge. In the US, video interventions have been successful at improving education about cancer clinical trials among minority patients. Thus, this study aimed to apply and adapt video interventions addressing attitudinal barriers peculiar to Nigerian patients. Methods: A hospital-based representative mixed-method study was conducted at the Lagos State University Teaching Hospital (LASUTH) from July to December 2020, comprising of cancer patients aged 18 and above. Patients were randomly selected during every clinic day, of which 63 patients volunteered to participate in this study. We first administered a cancer literacy survey to determine patients’ knowledge about clinical trials. For patients who had prior knowledge, a pre-intervention test was administered, after which a 15-minute video (attitudes and intention to enroll in therapeutic clinical trials (AIET)) to improve patients’ knowledge, perception, and attitudes towards clinical trials was played, and then ended by administering a post-intervention test to the patients. For patients who had no prior knowledge, the AIET video was played for them, followed by the post-intervention test. Results: Out of 63 patients sampled, 43 (68.3%) had breast cancer. On average, patients agreed to understand their cancer diagnosis and treatment very well. 84.1% of patients had never heard about cancer clinical trials, and 85.7% did not know what cancer clinical trials were. There was a strong positive relationship (r=0.916) between the pretest and posttest, which means that the intervention improved patients’ knowledge, perception, and attitudes about cancer clinical trials. In the focus groups, patients recommended adapting the video in Nigerian settings and representing all religions in order to address trust in local clinical trialists. Conclusion: Due to the small size of patients, change in clinical trial knowledge was not statistically significant. However, there is a trend suggesting that culturally adapted video interventions can be used to improve knowledge and perception about cancer clinical trials.

Keywords: clinical trials, culturally targeted intervention, patient education, video intervention

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Authors: Natalia Koltovaya, Nadezhda Zhuchkina, Ksenia Lyubimova

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We study the biological effects induced by ionizing radiation in view of therapeutic exposure and the idea of space flights beyond Earth's magnetosphere. In particular, we examine the differences between base pair substitution induction by ionizing radiation in model haploid and diploid yeast Saccharomyces cerevisiae cells. Such mutations are difficult to study in higher eukaryotic systems. In our research, we have used a collection of six isogenic trp5-strains and 14 isogenic haploid and diploid cyc1-strains that are specific markers of all possible base-pair substitutions. These strains differ from each other only in single base substitutions within codon-50 of the trp5 gene or codon-22 of the cyc1 gene. Different mutation spectra for two different haploid genetic trp5- and cyc1-assays and different mutation spectra for the same genetic cyc1-system in cells with different ploidy — haploid and diploid — have been obtained. It was linear function for dose-dependence in haploid and exponential in diploid cells. We suggest that the differences between haploid yeast strains reflect the dependence on the sequence context, while the differences between haploid and diploid strains reflect the different molecular mechanisms of mutations.

Keywords: base pair substitutions, γ-rays, haploid and diploid cells, yeast Saccharomyces cerevisiae

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Authors: Zdravko Trivic, John Chye Fung, Ruzica Bozovic-Stamenovic

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Within the context of rapidly ageing population in Singapore and the pressing demands on both caregivers and care providers, an integrated approach to ageing-friendly and ability-sensitive enabling environment becomes an imperative. This particularly applies to nursing home environments and their immediate surroundings, as they are becoming one of the main available options of long-term care for many senior adults who are unable to age at home. Yet, despite the considerable efforts to break the still predominant clinical approach to eldercare and to introduce more home-like design and person-centric care model, nursing homes keep being stigmatised and perceived as not so desirable environments to grow old in. The challenges are further emphasised by the associated physical, sensorial, psychological and cognitive declines that are the common consequences of ageing. Such declines have an immense impact on almost all aspects of older adults’ daily functioning, including problems with mobility and spatial orientation, difficulties in communication, withdrawal from social interaction, higher level of depression and decreased sense of independence and autonomy. However, typical nursing home designs tend to neglect the full capacities of balanced and carefully integrated multisensory stimuli as active component of care and ability building. This paper outlines part of a larger multi-disciplinary study of six nursing homes in Singapore, with overarching objectives to create new models of supportive nursing home environments that go beyond the clinical care model and encourage community integration with the nursing home settings. The paper focuses on the largely neglected aspects of sensorial comfort and multi-sensorial properties of nursing homes, including both indoor and immediate outdoor spaces (boundaries). The objective was to investigate the sensory rhythms and explore their role in nursing home users’ daily routine and therapeutic capacities. Socio-sensory rhythms were captured and analysed through a combination of on-site sensory recordings of “objective” quantitative sensory data (air temperature and humidity, sound level and luminance) using multi-function environment meter, perceived experienced data, spatial mapping, first-person observations of nursing home users’ activity patterns, and interviews. This was done in addition to employment of available assessment tools, such as Wisconsin Person Directed Care assessment tool, Dementia Quality of Life [DQoL] instrument, and Resident Environment Impact Scale [REIS], as these tools address the issues of sensorial experience insufficiently and selectively. Key findings indicate varied levels of sensory comfort, as well as diversity, intensity, and customisation of multi-sensory conditions within different nursing home spaces. Sensory stimulation is typically concentrated in communal living areas of the nursing homes or in the areas that often provide controlled or limited access, including specifically designed sensory rooms and outdoor green spaces (gardens and terraces). Opportunities for sensory stimulation are particularly limited for bed-bound senior residents and within more functional areas, such as corridors. This suggests that the capacities of nursing home designs to provide more diverse and better integrated pleasant sensory conditions as integrated “therapeutic devices” to build nursing home residents’ physical and mental abilities, encourage activity and improve wellbeing are far from exhausted.

Keywords: ageing-supportive environment, enabling design, multi-sensory assessment, nursing home environment

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Authors: Sergio D’Ambrosioa, Azza Dobousa, Chiara Schiraldia, Donatella Ciminib

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Probiotics are living microorganisms that give beneficial effects while consumed. Lactic acid bacteria and bifidobacteria are among the most representative strains assessed as probiotics and exploited as food supplements. Numerous studies demonstrated their potential as a therapeutic candidate for a variety of diseases (restoring gut flora, lowering cholesterol, immune response-enhancing, anti-inflammation and anti-oxidation activities). These beneficial actions are also due to biomolecules produced by probiotics, such as exopolysaccharides (EPSs), that demonstrate plenty of beneficial properties such as antimicrobial, antitumor, anti-biofilm, antiviral and immunomodulatory activities. Limosilactobacillus fermentum is a widely studied member of probiotics; however, few data are available on the development of fermentation and downstream processes for the production of viable biomasses for potential industrial applications. However, few data are available on the development of fermentation processes for the large-scale production of probiotics biomass for industrial applications and for purification processes of EPSs at an industrial scale. For this purpose, L. fermentum strain was isolated from buffalo milk and used as a test example for biotechnological process development. The strain was able to produce up to 109 CFU/mL on a (glucose-based) semi-defined medium deprived of animal-derived raw materials up to the pilot scale (150 L), demonstrating improved results compared to commonly used, although industrially not suitable, media-rich of casein and beef extract. Biomass concentration via microfiltration on hollow fibers, and subsequent spray-drying allowed to recover of about 5.7 × 1010CFU/gpowder of viable cells, indicating strain resistance to harsh processing conditions. Overall, these data demonstrate the possibility of obtaining and maintaining adequate levels of viable L. fermentum cells by using a simple approach that is potentially suitable for industrial development. A downstream EPS purification protocol based on ultrafiltration, precipitation and activated charcoal treatments showed a purity of the recovered polysaccharides of about 70-80%.

Keywords: probiotics, fermentation, exopolysaccharides (EPSs), purification

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Authors: Muhammad Mustaqeem, Musa Kaleem Baloch, Irfan Ullah, Ammarah Luqman, Afshan Ahmad

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Flurbiprofen is one of the most potent nonsteroidal anti-inflammatory drugs. It is widely used for relief of pain in patients suffering from rheumatic diseases, migraine, sore throat and primary dysmenorrhea. However, its aqueous solubility is very low and hinders the skin permeation. Thus, it is imperative to develop such a drug delivery systems which can improve its aqueous solubility and hence improve the skin permeation and therapeutic compliance. Microemulsions have been also proven to increase the cutaneous absorption of lipophilic drugs as compared to conventional vehicles. Micro-emulsion is thermodynamically stable emulsion that has the capacity to ‘hide/solubilize’ water-insoluble molecules within a continuous oil phase. Therefore, flurbiprofen was converted to Easters through chemical reactions with alcohols such as methanol, ethanol, propanol and butanol. The product was further treated with hydrazine to get hydrazide. The solubility of the parent drug Flurbiprofen and the products were solubilized in microemulsions formed using various surfactants like ionic, non-ionic and zwitterions. It has been concluded that the product was more soluble than the parent compound. The biological activities of these were also investigated. The outcome was very promising and the product was more active than the parent compound. It, therefore, concluded that in this way, we can not only enhance the solubility of the drug and increase its bioactivity, but also reduce the risk of stomach cancer.

Keywords: Flurbiprofen, microemulsion, surfactants, hyrazides

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Authors: P. Narrima, C. Y. Looi, M. A. Mohd, H. M. Ali

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Persea declinata (Bl.) Kosterm is a member of the Lauraceae family, widely distributed in Southeast Asia. It is from the same genus with avocado (Persea americana Mill), which is widely consumed as food and for medicinal purposes. In the present study, we examined the anticancer properties of Persea declinata (Bl.) Kosterm bark methanolic crude extract (PDM). PDM exhibited a potent antiproliferative effect in MCF-7 human breast cancer cells, with an IC50 value of 16.68 µg/mL after 48h of treatment. We observed that PDM caused cell cycle arrest and subsequent apoptosis in MCF-7 cells, as exhibited by increased population at G0/G1 phase, higher lactate dehydrogenase (LDH) release, and DNA fragmentation. Mechanistic studies showed that PDM caused significant elevation in ROS production, leading to perturbation of mitochondrial membrane potential, cell permeability, and activation of caspases-3/7. On the other hand, real-time PCR and Western blot analysis showed that PDM treatment increased the expression of the proapoptotic molecule, Bax, but decreased the expression of prosurvival proteins, Bcl-2 and Bcl-xL, in a dose-dependent manner. These findings imply that PDM could inhibit proliferation in MCF-7 cells via cell cycle arrest and apoptosis induction, indicating its potential as a therapeutic agent worthy of further development.

Keywords: antiproliferative, apoptosis, MCF-7 human breast cancer, Persea declinata

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Authors: Abdul Musaweer Habib, Habibul Hasan Mazumder, Saiful Islam, Sohel Sikder, Omar Faruk Sikder

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The plethora of genome sequence information of bacteria in recent times has ushered in many novel strategies for antibacterial drug discovery and facilitated medical science to take up the challenge of the increasing resistance of pathogenic bacteria to current antibiotics. In this study, we adopted subtractive genomics approach to analyze the whole genome sequence of the Fusobacterium nucleatum, a human oral pathogen having association with colorectal cancer. Our study divulged 1499 proteins of Fusobacterium nucleatum, which has no homolog in human genome. These proteins were subjected to screening further by using the Database of Essential Genes (DEG) that resulted in the identification of 32 vitally important proteins for the bacterium. Subsequent analysis of the identified pivotal proteins, using the KEGG Automated Annotation Server (KAAS) resulted in sorting 3 key enzymes of F. nucleatum that may be good candidates as potential drug targets, since they are unique for the bacterium and absent in humans. In addition, we have demonstrated the 3-D structure of these three proteins. Finally, determination of ligand binding sites of the key proteins as well as screening for functional inhibitors that best fitted with the ligands sites were conducted to discover effective novel therapeutic compounds against Fusobacterium nucleatum.

Keywords: colorectal cancer, drug target, Fusobacterium nucleatum, homology modeling, ligands

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Authors: Zhongyang Sun, Shu Zhang, Manjiang Xie

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Emerging evidence indicates that microRNAs (miRNAs) play important roles in modulating osteoblast function and bone formation. However, the influence of miRNA on osteoblast proliferation and the possible mechanisms underlying remain to be defined. In this study, we aimed to investigate whether miR-103 regulates osteoblast proliferation under simulated microgravity condition through regulating Cav1.2, the primary subunit of L-type voltage sensitive calcium channels (LTCCs). We first investigated the effect of simulated microgravity on osteoblast proliferation and the outcomes clearly demonstrated that the mechanical unloading inhibits MC3T3-E1 osteoblast-like cells proliferation. Using quantitative Real-Time PCR (qRT-PCR), we provided data showing that miR-103 was up-regulated in response to simulated microgravity. In addition, we observed that up-regulation of miR-103 inhibited and down-regulation of miR-103 promoted osteoblast proliferation under simulated microgravity condition. Furthermore, knocking-down or over-expressing miR-103, respectively, up- or down-regulated the level of Cav1.2 expression and LTCCs currents, suggesting that miR-103 acts as an endogenous attenuator of Cav1.2 in osteoblasts under the condition of simulated microgravity. More importantly, we showed that the effect of miR-103 on osteoblast proliferation was diminished in simulated microgravity, when co-transfecting miR-103 mimic or inhibitor with Cav1.2 siRNA. Taken together, our data suggest that miR-103 inhibits osteoblast proliferation mainly through suppression of Cav1.2 expression under simulated microgravity condition. This work may provide a novel mechanism of microgravity-induced detrimental effects on osteoblast, identifying miR-103 as a novel possible therapeutic target in bone remodeling disorders in this mechanical unloading.

Keywords: microRNA, osteoblasts, cell proliferation, Cav1.2, simulated microgravity

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Authors: Mrinal Gupta, Mohammad Rumman, Babita Singh Abbas Ali Mahdi, Shivani Pandey

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Introduction: Berberine (BBR), a bioactive compound isolated from Coptidis Rhizoma, possesses diverse pharmacological activities, including anti-bacterial, anti-inflammatory, antitumor, hypolipidemic, and anti-diabetic. However, its role as an anti-diabetic agent in animal models of dexamethasone (Dex)-induced diabetes remains unknown. Studies have shown that natural compounds, including aloe, caper, cinnamon, cocoa, green and black tea, and turmeric, can be used for treating Type 2 diabetes mellitus (DM). Compared to conventional drugs, natural compounds have fewer side effects and are easily available. Herein, we studied the anti-diabetic effects of BBR in a mice model of Dex-induced diabetes. Methods: HepG2 cell line was used for glucose release and glycogen synthesis studies. Cell proliferation was measured by methylthiotetrazole (MTT) assay. For animal studies, mice were treated with Dex (2 mg/kg, i.m.) for 30 days and the effect of BBR at the doses 100, 200, and 500 mg/kg (p.o.) was analyzed. Glucose, insulin, and pyruvate tests were performed to evaluate the development of the diabetic model. An echo MRI was performed to assess the fat mass. Further, to elucidate the mechanism of action of BBR, mRNA expression of genes regulating gluconeogenesis, glucose uptake, and glycolysis were analyzed. Results: In vitro BBR had no impact on cell viability up to a concentration of 50μM. Moreover, BBR suppressed the hepatic glucose release and improved glucose tolerance in HepG2 cells. In vivo, BBR improved glucose homeostasis in diabetic mice, as evidenced by enhanced glucose clearance, increased glycolysis, elevated glucose uptake, and decreased gluconeogenesis. Further, Dex treatment increased the total fat mass in mice, which was ameliorated by BBR treatment. Conclusion: BBR improves glucose tolerance by increasing glucose clearance, inhibiting hepatic glucose release, and decreasing obesity. Thus, BBR may become a potential therapeutic agent for treating glucocorticoid-induced diabetes and obesity in the future.

Keywords: glucocorticoid, hyperglycemia, berberine, HepG2 cells, insulin resistance, glucose

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Authors: Saji George, Eng Khuan Seng, Christof Luda

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Nanotechnology has been recognized as an important tool for modern agriculture and has the potential to overcome some of the pressing challenges faced by aquaculture industry. A strategy for optimizing nanotechnology-based therapeutic delivery platform for immunizing farmed fish was developed. Accordingly, a compositional library of nanomaterials of natural chemistry (Halloysite (clay), Chitosan, Hydroxyapatite, Mesoporous Silica and a composite material of clay-chitosan) was screened for their toxicity and efficiency in delivering models antigens in cellular and zebrafish embryo models using high throughput screening platforms. Through multi-parametric optimization, chitosan modified halloysite (clay) nanomaterial was identified as an optimal vaccine delivery platform. Further, studies conducted in juvenile seabass showed the potential of clay-chitosan in delivering outer membrane protein of Tenacibaculum maritimum- TIMA (pathogenic bacteria) to and its efficiency in eliciting immune responses in fish. In short, as exemplified by this work, the strategy of using compositional nanomaterial libraries and their biological profiling using high-throughput screening platform could fasten the discovery process of nanomaterials with potential applications in food and agriculture.

Keywords: nanotechnology, fish-vaccine, drug-delivery, halloysite-chitosan

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Authors: Michela Terlizzi, Chiara Colarusso, Aldo Pinto, Rosalinda Sorrentino

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Sphingosine-1-phosphate (S1P) is a membrane-derived bioactive phospholipid exerting a multitude of effects on respiratory cell physiology and pathology through five S1P receptors (S1PR1-5). Higher levels of S1P have been registered in a broad range of respiratory diseases, including inflammatory disorders and cancer, although its exact role is still elusive. Based on our previous study in which we found that S1P/S1PR3 is involved in an inflammatory pattern via the activation of Toll-like Receptor 9 (TLR9), highly expressed on lung cancer cells, the main goal of the current study was to better understand the involvement of S1P/S1PR3 pathway/signaling during lung carcinogenesis, taking advantage of a mouse model of first-hand smoke exposure and of carcinogen-induced lung cancer. We used human samples of Non-Small Cell Lung Cancer (NSCLC), a mouse model of first-hand smoking, and of Benzo(a)pyrene (BaP)-induced tumor-bearing mice and A549 lung adenocarcinoma cells. We found that the intranuclear, but not the membrane, localization of S1PR3 was associated to the proliferation of lung adenocarcinoma cells, the mechanism that was correlated to human and mouse samples of smoke-exposure and carcinogen-induced lung cancer, which were characterized by higher utilization of S1P. Indeed, the inhibition of the membrane S1PR3 did not alter tumor cell proliferation after TLR9 activation. Instead, according to the nuclear localization of sphingosine kinase (SPHK) II, the enzyme responsible for the catalysis of the S1P last step synthesis, the inhibition of the kinase completely blocked the endogenous S1P-induced tumor cell proliferation. These results prove that the endogenous TLR9-induced S1P can on one side favor pro-inflammatory mechanisms in the tumor microenvironment via the activation of cell surface receptors, but on the other tumor progression via the nuclear S1PR3/SPHK II axis, highlighting a novel molecular mechanism that identifies S1P as one of the crucial mediators for lung carcinogenesis-associated inflammatory processes and that could provide differential therapeutic approaches especially in non-responsive lung cancer patients.

Keywords: sphingosine-1-phosphate (S1P), S1P Receptor 3 (S1PR3), smoking-mice, lung inflammation, lung cancer

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Authors: Adisu Mengesha Assefa

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The field of cardiovascular care is being transformed by the incorporation of Virtual Reality (VR), Augmented Reality (AR), and Mixed Reality (MR), collectively known as Extended Reality (XR), into medical education, procedural planning, and patient care. This review examines the state-of-the-art applications of XR in cardiology, emphasizing its role in enhancing the precision of interventional procedures and understanding complex anatomical structures. XR technologies complement conventional imaging methods by enabling immersive three-dimensional interaction that facilitates both preoperative planning and intraoperative guidance. Despite these promising developments, challenges such as harmonizing data, integrating various imaging systems, and addressing the prevalence of cybersickness remain. Ethical considerations, including maintaining physician focus and ensuring patient safety, are crucial when implementing XR in clinical settings. This review summarizes the existing literature and highlights the need for more rigorous future studies to validate therapeutic benefits and ensure safe application. By examining both the potential and the challenges, this paper aims to delineate the current and future roles of XR in cardiovascular care, emphasizing the necessity for continued innovation and ethical oversight to improve patient outcomes.

Keywords: virtual reality, augmented reality, mixed reality, cardiovascular care, education, preprocedural planning, intraoperative guidance, postoperative patient rehabilitation

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Authors: Syue-Liang Lin, C. Allen Chang

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Luminescence imaging is an important technique used in biomedical research and clinical diagnostic applications in recent years. Concurrently, the development of NIR luminescence probes / imaging contrast agents has helped the understanding of the structural and functional properties of cells and animals. Photodynamic therapy (PDT) is used clinically to treat a wide range of medical conditions, but the therapeutic efficacy of general PDT for deeper tumor was limited by the penetration of excitation source. The tumor targeting biomedical nanomaterials UCNP@PS (upconversion nanoparticle conjugated with photosensitizer) for photodynamic therapy and near-infrared imaging of cancer will be developed in our study. Synthesis and characterization of biomedical nanomaterials were completed in this studies. The spectrum of UCNP was characterized by photoluminescence spectroscopy and the morphology was characterized by Transmission Electron Microscope (TEM). TEM and XRD analyses indicated that these nanoparticles are about 20~50 nm with hexagonal phase. NaYF₄:Ln³⁺ (Ln= Yb, Nd, Er) upconversion nanoparticles (UCNPs) with core / shell structure, synthesized by thermal decomposition method in 300°C, have the ability to emit visible light (upconversion: 540 nm, 660 nm) and near-infrared with longer wavelength (downconversion: NIR: 980 nm, 1525 nm) by absorbing 800 nm NIR laser. The information obtained from these studies would be very useful for applications of these nanomaterials for bio-luminescence imaging and photodynamic therapy of deep tumor tissue in the future.

Keywords: Near Infrared (NIR), lanthanide, core-shell structure, upconversion, theranostics

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Authors: Yen-Ni Teng, Hsing-Yi Chen, Hsien-An Pan, Yung-Ming Lin, Hany A. Omar, Jui-Hsiang Hung

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Leucine-rich repeats and WD repeat domain containing 1 (LRWD1) is highly expressed in the testes of healthy males. On the other hand, LRWD1 is significantly down-regulated in the testicular tissues of patients with severe spermatogenic defects. In our study, the downregulation of LRWD1 expression by shRNA caused a significant reduction of cell growth and mitosis and a noteworthy increase in the cell microtubule atrophy rate. Here, we used EMBOSS CpG plot analysis to explore the promoter region of LRWD1 gene. We found that CpG islands are located between positions -253 to +5 nucleotides upstream from the LRWD1 transcription start site. Luciferase reporter assay revealed that the hypermethylation of the LRWD1 promoter reduced the transcription activity in cells. In addition, quantitative methylation-specific PCR and immunostaining showed that the methylation inhibitor, 5-Aza-2'-deoxycytidine, increased LRWD1 promoter activity, LRWD1 mRNA, protein expression and cell viability. Whereas, the methylation activator, S-adenosylmethionine, caused opposite effects. The overexpression of p53 and Nrf2 in NT2/D1 cells increased LRWD1 promoter activity while 5-fluorodeoxyuridine decreased it. In conclusion, this study highlights evidence that the methylation status of LRWD1 promoter is associated with LRWD1 expression. Since the expression level of LRWD1 plays an important role in spermatogenesis, the methylation status of LRWD1 may serve as a novel molecular diagnostic or therapeutic approach in male's infertility.

Keywords: LRWD1, DNA methylation, p53, Nrf2

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Authors: Deeba N. Baig, Ateeqa Ijaz, Saloome Rafiq

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Camel is a religious and culturally significant animal in Asian and African regions. In Pakistan Dromedary and Bactrian are common camel breeds. Other than the transportation use, it is a pivotal source of milk and meat. The quality of its milk and meat is predominantly dependent on the geographical location and variety of vegetation available for the diet. Camel milk (CM) is highly nutritious because of its reduced cholesterol and sugar contents along with enhanced minerals and vitamins level. The absence of beta-lactoglobulin (like human milk), makes CM a safer alternative for infants and children having Cow Milk Allergy (CMA). In addition to this, it has a unique probiotic profile both in raw and fermented form. Number of Lactic acid bacteria (LAB) including lactococcus, lactobacillus, enterococcus, streptococcus, weissella, pediococcus and many other bacteria have been detected. From these LAB Lactobacilli, Bifidobacterium and Enterococcus are widely used commercially for fermentation purpose. CM has high therapeutic value as its effectiveness is known against various ailments like fever, arthritis, asthma, gastritis, hepatitis, Jaundice, constipation, postpartum care of women, anti-venom, dropsy etc. It also has anti-diabetic, anti-microbial, antitumor potential along with its robust efficacy in the treatment of auto-immune disorders. Recently, the role of CM has been explored in brain-gut axis for the therapeutics of neurodevelopmental disorders. In this connection, a lot of grey area was available to explore the probiotics and therapeutics latent in the CM available in Pakistan. Thus, current study was designed to explore the predominant probiotic flora and antimicrobial potential of CM from different local breeds of Pakistan. The probiotics have been identified through biochemical, physiological and ribo-typing methods. In addition to this, bacteriocins (antimicrobial-agents) were screened through PCR-based approach. Results of this study revealed that CM from different breeds of camel depicted a number of similar probiotic candidates along with the range of limited variability. However, the nucleotide sequence analysis of selected anti-listerial bacteriocins exposed least variability. As a conclusion, the CM has sufficient probiotic availability and significant anti-microbial potential.

Keywords: bacteriocins, camel milk, probiotics potential, therapeutics

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Authors: Ledi Neçaj

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Introduction: Cardio-respiratory rehabilitation is the set of coordinated interventions needed to provide the best physical, psychological, and social conditions so that patients with chronic or post-acute cardiopulmonary disease, with their efforts, maintain or resume optimal functioning in society through improved health behaviors. Purpose: To study the effectiveness of the application of Cardio-Respiratory Rehabilitation in the typology of patients with chronic or post-acute cardiomyopathy and chronic respiratory diseases in order to facilitate their therapeutic use and to improve the overall quality of life. Material and Method: This is a prospective study including patients with COPD and cardiac disease who were included in the rehabilitation program during the period January 2019 - November 2021. The study was conducted at the University Hospital Center "Mother Teresa" in Tirana, University Hospital "SHEFQET NDROQI", AMERICAN Hospital, HYGEA Hospital, and "Our Lady of Good Counsel, Tirana". An individual chart was used to collect sociodemographic, physical, clinical, and functional examinations for each patient. Results: The study included 253 patients, with a mean age of 62.1 (± 7.9) years, ranging from 48 to 82 years. (67.6%) of the patients were males, and (32.4%) female. Male patients predominated in all age groups, with a statistically significant difference with females (p<0.01). The most common cardiac pathologies are coronary artery bypass (24%), cerebral stroke (9%), myocardial infarction (17%), Stent placement (8%) (p<0.01). Correlation matrix of risk factors found a significant correlation of alcohol consumption with diabetes, smoking, dyslipidemia, sedentary life, obesity, AVC, and hypertension. Functional capacity estimated by change in metabolic equivalents (MET) improved by 46% from 4. ±2.2 to 7.2± .8 METs (p<0.01). Duration of exercise after rehabilitation was increased by 21% compared to baseline (p<0.01). The mean score of all three subscales of the questionnaire: symptoms (p=0.03), activity (p<0.01), and impact (p<0.01) after rehabilitation, was lower compared to pre-rehabilitation. Conclusions: The rehabilitation program has impacted on improving the quality of life, reducing symptoms, reducing the impact of negative factors on daily life, and reducing dyspnea during daily activities.

Keywords: cardio-respiratory rehabilitation, physical exercise, quality of life, diseases

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Authors: Deepthy Ann Joy, N. Sreedevi

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Hearing impairment (HI) at an early age, identified before the onset of language development can reduce the negative effect on speech and language development of children. Early rehabilitation is very important in the improvement of speech production in children with HI. Other than conventional hearing aids, Cochlear Implants are being used in the rehabilitation of children with HI. However, delay in acquisition of speech and language milestones persist in children with Cochlear Implant (CI). Delay in speech milestones are reflected through speech sound errors. These errors reflect the temporal and spectral characteristics of speech. Hence, acoustical analysis of the speech sounds will provide a better representation of speech production skills in children with CI. The present study aimed at investigating the acoustic characteristics of vowels in Malayalam speaking children with a cochlear implant. The participants of the study consisted of 20 Malayalam speaking children in the age range of four and seven years. The experimental group consisted of 10 children with CI, and the control group consisted of 10 typically developing children. Acoustic analysis was carried out for 5 short (/a/, /i/, /u/, /e/, /o/) and 5 long vowels (/a:/, /i:/, /u:/, /e:/, /o:/) in word-initial position. The responses were recorded and analyzed for acoustic parameters such as Vowel duration, Ratio of the duration of a short and long vowel, Formant frequencies (F₁ and F₂) and Formant Centralization Ratio (FCR) computed using the formula (F₂u+F₂a+F₁i+F₁u)/(F₂i+F₁a). Findings of the present study indicated that the values for vowel duration were higher in experimental group compared to the control group for all the vowels except for /u/. Ratio of duration of short and long vowel was also found to be higher in experimental group compared to control group except for /i/. Further F₁ for all vowels was found to be higher in experimental group with variability noticed in F₂ values. FCR was found be higher in experimental group, indicating vowel centralization. Further, the results of independent t-test revealed no significant difference across the parameters in both the groups. It was found that the spectral and temporal measures in children with CI moved towards normal range. The result emphasizes the significance of early rehabilitation in children with hearing impairment. The role of rehabilitation related aspects are also discussed in detail which can be clinically incorporated for the betterment of speech therapeutic services in children with CI.

Keywords: acoustics, cochlear implant, Malayalam, vowels

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Authors: R. P. Hewawasam, A. F. Dulhunty

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The ryanodine receptor (RyR) is an intracellular ion channel that releases Ca2+ from the sarcoplasmic reticulum and is essential for the excitation-contraction coupling and contraction in striated muscle. Human muscle specific glutathione transferase M2-2 (GSTM2-2) is a highly specific inhibitor of cardiac ryanodine receptor (RyR2) activity. Single channel-lipid bilayer studies and Ca2+ release assays performed using the C-terminal half of the GSTM2-2 and its mutants F157A and Y160A confirmed the ability of the C terminal domain of GSTM2-2 to specifically inhibit the cardiac ryanodine receptor activity. Objective of the present study is to determine the effect of C terminal domain of GSTM2-2 (GSTM2-2C) and the mutants, F157A and Y160A on the Ca2+ transients of neonatal ventricular cardiomyocytes. Primary cardiomyocytes were cultured from neonatal rats. They were treated with GSTM2-2C and the two mutants F157A and Y160A at 15µM and incubated for 2 hours. Then the cells were led with Fluo-4AM, fluorescent Ca2+ indicator, and the field stimulated (1 Hz, 3V and 2ms) cells were excited using the 488 nm argon laser. Contractility of the cells were measured and the Ca2+ transients in the stained cells were imaged using Leica SP5 confocal microscope. Peak amplitude of the Ca2+ transient, rise time and decay time from the peak were measured for each transient. In contrast to GSTM2C which significantly reduced the % shortening (42.8%) in the field stimulated cells, F157A and Y160A failed to reduce the % shortening.Analysis revealed that the average amplitude of the Ca2+ transient was significantly reduced (P<0.001) in cells treated with the wild type GSTM2-2C compared to that of untreated cells. Cells treated with the mutants F157A and Y160A didn’t change the Ca2+ transient significantly compared to the control. A significant increase in the rise time (P< 0.001) and a significant reduction in the decay time (P< 0.001) were observed in cardiomyocytes treated with GSTM2-2C compared to the control but not with F157A and Y160A. These results are consistent with the observation that GSTM2-2C reduced the Ca2+ release from the cardiac SR significantly whereas the mutants, F157A and Y160A didn’t show any effect compared to the control. GSTM2-2C has an isoform-specific effect on the cardiac ryanodine receptor activity and also it inhibits RyR2 channel activity only during diastole. Selective inhibition of RyR2 by GSTM2-2C has significant clinical potential in the treatment of cardiac arrhythmias and heart failure. Since GSTM2-2C-terminal construct has no GST enzyme activity, its introduction to the cardiomyocyte would not exert any unwanted side effects that may alter its enzymatic action. The present study further confirms that GSTM2-2C is capable of decreasing the Ca2+ release from the cardiac SR during diastole. These results raise the future possibility of using GSTM2-2C as a template for therapeutics that can depress RyR2 function when the channel is hyperactive in cardiac arrhythmias and heart failure.

Keywords: arrhythmia, cardiac muscle, cardiac ryanodine receptor, GSTM2-2

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Authors: Mohammad Hossein Modarressi, Mozhgan Mondeali, Khabat Barkhordari, Ali Etemadi

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The COVID-19 pandemic, caused by SARS-CoV-2, has led to significant concerns worldwide due to its catastrophic effects on public health. The SARS-CoV-2 infection is initiated with the binding of the receptor-binding domain (RBD) in its spike protein to the ACE2 receptor in the host cell membrane. Due to the error-prone entity of the viral RNA-dependent polymerase complex, the virus genome, including the coding region for the RBD, acquires new mutations, leading to the appearance of multiple variants. These variants can potentially impact transmission, virulence, antigenicity and evasive immune properties. S477N mutation located in the RBD has been observed in the SARS-CoV-2 omicron (B.1.1. 529) variant. In this study, we investigated the consequences of S477N mutation at the molecular level using computational approaches such as molecular dynamics simulation, protein-protein interaction analysis, immunoinformatics and free energy computation. We showed that displacement of Ser with Asn increases the stability of the spike protein and its affinity to ACE2 and thus increases the transmission potential of the virus. This mutation changes the folding and secondary structure of the spike protein. Also, it reduces antibody neutralization, raising concern about re-infection, vaccine breakthrough and therapeutic values.

Keywords: S477N, COVID-19, molecular dynamic, SARS-COV2 mutations

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Authors: Zayre I. Gonzalez-Acevedo, Marco A. Garcia-Zarate

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Environmental pollution by heavy metals is due to several processes, whether natural as weathering, or anthropogenic, related to human activities. Geysers may content dissolved heavy metals, related with their geothermal origin, and they are widely used by local people and tourists for treatment of dermal diseases and other therapeutic applications. In this study, 20 geysers with temperatures between 32 to 94 °C, located in the vicinity of Queretaro and Guanajuato in Central Mexico, were studied. These geysers were sampled in dry and rainy seasons in order to investigate seasonal changes of trace elements. The samples were analyzed in SWAMP Lab, University of Alberta, Canada for 34 elements. Most of the analyzed trace elements sowed concentrations below guidelines for natural waters. The elements showed seasonal variability with higher concentrations during rainy season. Arsenic varied from 49.29 to 2.16 µg L⁻¹. Arsenic was highly correlated with Fe, Sr, Th and Tl. Barium varied from 93.52 to 1.79 µg L⁻¹. Barium was highly correlated with Co, Cr, Mo, Ni, U, V, and Y. Copper and Zinc were correlated as well. According to the comparison of sites and the correlations between trace elements, their source was identified as natural regional, geothermal or anthropogenic origin. Because of application of geyser's water to balneology and health treatments, and also, because they are located in an urban zone in development, advise on their direct uses, according to their environmental quality is appointed in this research.

Keywords: balneology, direct uses, environmental quality and trace elements

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