Search results for: drug therapy problems

Authors: Poteet Frances, Glovinski Ira

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INTRODUCTION: The interoceptive nervous system continuously senses chemical and anatomical changes and helps you recognize, understand, and feel what’s going on inside your body so it is important for energy regulation, memory, affect, and sense of self. A newborn needs predictable routines rather than confusion/chaos to make connections between internal experiences and emotions. AIM: Current legal protocols of removing babies from drug-addicted mothers impact the critical window of bonding. The newborn’s brain is social and the attachment process influences a child’s development which begins immediately after birth through nourishment, comfort, and protection. DESCRIPTION: Our project aims to educate drug-addicted mothers, and medical, nursing, and social work professionals on interoceptive concepts and practices to sustain the mother/newborn relationship. A mother’s interoceptive knowledge predicts children’s emotion regulation and social skills in middle childhood. CONCLUSION: When mothers develop an awareness of their inner bodily sensations, they can self-regulate and be emotionally available to co-regulate (support their newborn during distressing emotions and sensations). Our project has enhanced relationship preservation (mothers understand how their presence matters) and the overall mother/newborn connection.

Keywords: drug-addiction, interoception, legal, mothers, newborn, self-regulation

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Authors: Pei-Wen Lin, Ta-I Yang

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Cancer has been one of the leading causes of human death for centuries. Considerable effort has been devoted to developing new treatments to reduce and control cancers. Magnetic particle hyperthermia and near-infrared photothermal therapy are the promising strategies to treat cancers due to its effectiveness with only mild side effects. This study focused on synthesizing magnetic Ag@Fe3O4 nanoparticles applicable for both of magnetic hyperthermia and near-infrared photothermal therapy. The hydrophilic poly(diallyldimethylammonium chloride) polymer was utilized to prepare superparamagnetic Fe3O4 clusters and to promote silver nanoparticles grown on Fe3O4 surfaces, obtaining Ag@Fe3O4 nanoparticles. The morphology (shape and dimension) of Ag nanoparticles was subsequently tailored using commercial LED lights. Therefore, the resulting Ag@Fe3O4 nanoparticles can absorb specific wavelength of light ranging from 400 nm to 800 nm by adjusting the wavelength of LED lights and the free silver ions in reaction solution. Heating performance tests confirmed that the synthesized Ag@Fe3O4 nanoparticles show appreciable heating capability for both of magnetic particle hyperthermia and near-infrared photothermal therapy. The findings in this study could provide new ideas to design functional materials to treat cancers.

Keywords: light-emitting diode assisted synthesis, magnetic particles, photothermal materials, hyperthermia

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Authors: Kasra Afsahi, Maryam Soheilifar, S. Hossein Hosseini, Omid Seyed Esmaeili, Rouzbeh Kezemi, Noushin Mehrbod, Nazanin Vahed, Tahereh Hajiahmad, Noureddin Nakhostin Ansari

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Background: Stroke is a disabling neurological disease. Rehabilitative therapies are important treatment methods. This clinical trial was done to compare the effects of VR beside conventional rehabilitation versus conventional rehabilitation alone on spasticity and motor function in stroke patients. Materials and Methods: In this open-label randomized controlled clinical trial, 40 consecutive patients with stable first-ever ischemic stroke in the past three to 12 months that were referred to a rehabilitation clinic in Tehran, Iran, in 2020 were enrolled. After signing the informed written consent form, subjects were randomly assigned by block randomization of five in each block as cases with 1:1 into two groups of 20 cases; conventional plus VR therapy group: 45-minute conventional therapy session plus 15-minute VR therapy, and conventional group: 60-minute conventional therapy session. VR rehabilitation is designed and developed with different stages. Outcomes were modified Ashworth scale, recovery stage score for motor function, range of motion (ROM) of shoulder abduction/wrist extension, and patients’ satisfaction rate. Data were compared after study termination. Results: The satisfaction rate among the patients was significantly better in the combination group (P=0.003). Only wrist extension was varied between groups and was better in the combination group. The variables generally had a statistically significant difference (P < 0.05). Conclusion: Virtual reality plus conventional rehabilitation therapy is superior versus conventional rehabilitation alone on the wrist and elbow spasticity and motor function in patients with stroke.

Keywords: stroke, virtual therapy, rehabilitation, treatment

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Authors: Elena G. Salina, Laurent R. Chiarelli, Maria R. Pasca, Vadim A. Makarov

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Tuberculosis is one of the most challenging threats to human health, confronted by the problem of drug resistance. Evidently, new drugs for tuberculosis are urgently needed. Thienopyrimidine TP053 is one of the most promising new antitubercular prodrugs. Mycothiol-dependent reductase Mrx2, encoded by rv2466c, is known to be a TP053 activator; however, the precise mode of action of this compound remained unclear. Being highly active against both replicating and non-replicating tuberculosis bacilli, TP053 also revealed dose-escalating activity for M. tuberculosis-infected murine macrophages. The chemical structure of TP053 is characterized by the presence of NO₂ group which was suggested to be responsible for the toxic effects of the activated compound. Reduction of a nitroaromatic moiety of TP53 by Mrx2 was hypothesized to result in NO release. Analysis of the products of enzymatic activation of TP053 by Mrx2 by the Greiss reagent clearly demonstrated production of nitric oxide in a time-dependent manner. Mass-spectra of cell lysates of TP-treated M. tuberculosis bacilli demonstrated the transformation of TP053 to its non-active metabolite with Mw=261 that corresponds NO release. The mechanism of NO toxicity for bacteria includes DNA damage and degradation of iron-sulfur centers, especially under oxygen depletion. Thus, TP-053 drug-like scaffold is prospective for further development of novel anti-TB drug. This work was financially supported by the Russian Foundation for Basic Research (Grant 17-04-00342).

Keywords: drug discovery, M. tuberculosis, nitric oxide, NO donors

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Authors: Yang Yang, Luciana Magalhães Rebelo Alencar, Martha Sahylí Ortega Pijeira, Beatriz da Silva Batista, Alefe Roger Silva França, Erick Rafael Dias Rates, Ruana Cardoso Lima, Sara Gemini-Piperni, Ralph Santos-Oliveira

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Radium-²²³ dichloride ([²²³Rₐ]RₐCl₂) is an alpha particle-emitting radiopharmaceutical currently approved for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases, and no known visceral metastatic disease. [²²³Rₐ]RₐCl₂ is bone-seeking calcium mimetic that bonds into the newly formed bone stroma, especially osteoblastic or sclerotic metastases, killing the tumor cells by inducing DNA breaks in a potent and localized manner. Nonetheless, the successful therapy of osteosarcoma as primary bone tumors is still a challenge. Nanomicelles are colloidal nanosystems widely used in drug development to improve blood circulation time, bioavailability, and specificity of therapeutic agents, among other applications. In addition, the enhanced permeability and retention effect of the nanosystems, and the renal excretion of the nanomicelles reported in most cases so far, are very attractive to achieve selective and increased accumulation in tumor site as well as to increase the safety of [²²³Rₐ]RₐCl₂ in the clinical routine. In the present work, [²²³Rₐ]RₐCl₂ nanomicelles were produced, characterized, in vitro evaluated, and compared with pure [²²³Rₐ]RₐCl2 solution using SAOS2 osteosarcoma cells. The [²²³Rₐ]RₐCl₂ nanomicelles were prepared using the amphiphilic copolymer Pluronic F127. The dynamic light scattering analysis of freshly produced [²²³Rₐ]RₐCl₂ nanomicelles demonstrated a mean size of 129.4 nm with a polydispersity index (PDI) of 0.303. After one week stored in the refrigerator, the mean size of the [²²³Rₐ]RₐCl₂ nanomicelles increased to 169.4 with a PDI of 0.381. Atomic force microscopy analysis of [223Rₐ]RₐCl₂ nanomicelles exhibited spherical structures whose heights reach 1 µm, suggesting the filling of 127-Pluronic nanomicelles with [²²³Rₐ]RₐCl₂. The viability assay with [²²³Rₐ]RₐCl₂ nanomicelles displayed a dose-dependent response as it was observed using pure [²²³Rₐ]RₐCl2. However, at the same dose, [²²³Rₐ]RₐCl₂ nanomicelles were 20% higher efficient in killing SAOS2 cells when compared with pure [²²³Rₐ]RₐCl₂. These findings demonstrated the effectiveness of the nanosystem validating the application of nanotechnology in targeted alpha therapy with [²²³Ra]RₐCl₂. In addition, the [²²³Rₐ]RaCl₂nanomicelles may be decorated and incorporated with a great variety of agents and compounds (e.g., monoclonal antibodies, aptamers, peptides) to overcome the limited use of [²²³Ra]RₐCl₂.

Keywords: nanomicelles, osteosarcoma, radium dichloride, targeted alpha therapy

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Authors: Alya A. Arabi

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Bioisosteres are functional groups that can be interchangeably used without affecting the potency of the drug. Bioisosteres have similar pharmacological properties. Bioisosterism is useful for modifying the physicochemical properties of a drug while obeying the Lipinski’s rules. Bioisosteres are key in optimizing the pharmacokinetic and pharmacodynamics properties of a drug. Tetrazole and carboxylate anions are non-classic bioisosteres. Density functional theory was used to obtain the wavefunction of the molecules and the optimized geometries. The quantum theory of atoms in molecules (QTAIM) was used to uncover the similarity of the average electron density in tetrazole and carboxylate anions. This similarity between the bioisosteres capped by a methyl group was valid despite the fact that the groups have different volumes, charges, energies, or electron populations. The biochemical correspondence of tetrazole and carboxylic acid was also determined to be a result of the similarity of the topography of the electrostatic potential (ESP). The ESP demonstrates the pharmacological and biochemical resemblance for a matching “key-and-lock” interaction.

Keywords: bioisosteres, carboxylic acid, density functional theory, electrostatic potential, tetrazole

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Authors: Mohamed A. Eid, Sobhy M. Aly

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Background: About 75% of children with spastic hemiplegic cerebral palsy walk independently, but most still show abnormal gait patterns because of contractures across the joints and muscle spasticity. Objective: The purpose of this study was to investigate and compare the effects of extracorporeal shock wave therapy (ESWT) versus functional electrical stimulation (FES) on spasticity, function, and gait parameters in children with hemiplegic cerebral palsy (CP). Methods: A randomized controlled trail was conducted for 45 children with hemiplegic CP ranging in age from 6 to 9 years. They were assigned randomly using opaque envelopes into three groups. Physical Therapy (PT) group consisted of 15 children and received the conventional physical therapy program (CPTP) in addition to ankle foot orthosis (AFO). ESWT group consisted of 15 children and received the CPTP, AFO in addition to ESWT. FES group also consisted of 15 children and received the CPTP, AFO in addition to FES. All groups received the program of treatment 3 days/week for 12 weeks. Evaluation of spasticity by using the Modified Ashworth Scale (MAS), function by using the Pediatric Evaluation Disability Inventory (PEDI) and gait parameters by using the 3-D gait analysis was conducted at baseline and after 12 weeks of the treatment program. Results: Within groups, significant improvements in spasticity, function, and gait (P = 0.05) were observed in both ESWT and FES groups after treatment. While between groups, ESWT group showed significant improvements in all measured variables compared with FES and PT groups (P ˂ 0.05) after treatment. Conclusion: ESWT induced significant improvement than FES in decreasing spasticity and improving function and gait in children with hemiplegic CP. Therefore, ESWT should be included as an adjunctive therapy in the rehabilitation program of these children.

Keywords: cerebral palsy, extracorporeal shock wave therapy, functional electrical stimulation, function, gait, spasticity

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Authors: Xiao-Yin Liu, Liang-Xue Zhou

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Traumatic brain injury (TBI), as a kind of nerve trauma caused by an external force, affects people all over the world and is a global public health problem. Although there are various clinical treatments for brain injury, including surgery, drug therapy, and rehabilitation therapy, the therapeutic effect is very limited. To improve the therapeutic effect of TBI, scaffolds combined with exosomes are a promising but challenging method for TBI repair. In this study, we examined whether a novel 3D-printed collagen/chitosan scaffold/exosomes derived from neural stem cells (NSCs) pretreated with insulin growth factor-1 (IGF-I) scaffolds (3D-CC-INExos) could be used to improve TBI repair and functional recovery after TBI. Our results showed that composite scaffolds of collagen-, chitosan- and exosomes derived from NSCs pretreated with IGF-I (INExos) could continuously release the exosomes for two weeks. In the rat TBI model, 3D-CC-INExos scaffold transplantation significantly improved motor and cognitive function after TBI, as assessed by the Morris water maze test and modified neurological severity scores. In addition, immunofluorescence staining and transmission electron microscopy showed that the recovery of damaged nerve tissue in the injured area was significantly improved by 3D-CC-INExos implantation. In conclusion, our data suggest that 3D-CC-INExos might provide a potential strategy for the treatment of TBI and lay a solid foundation for clinical translation.

Keywords: traumatic brain injury, exosomes, insulin growth factor-1, neural stem cells, collagen, chitosan, 3D printing, neural regeneration, angiogenesis, functional recovery

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Authors: Yuxiang Pan, Yong Qiu, Chenlei Gu, Ping Wang

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In the past decade, three-dimensional (3D) tumor cell models have attracted increasing interest in the field of drug screening due to their great advantages in simulating more accurately the heterogeneous tumor behavior in vivo. Drug sensitivity testing based on 3D tumor cell models can provide more reliable in vivo efficacy prediction. The gold standard fluorescence staining is hard to achieve the real-time and label-free monitoring of the viability of 3D tumor cell models. In this study, micro-groove impedance sensor (MGIS) was specially developed for dynamic and non-invasive monitoring of 3D cell viability. 3D tumor cells were trapped in the micro-grooves with opposite gold electrodes for the in-situ impedance measurement. The change of live cell number would cause inversely proportional change to the impedance magnitude of the entire cell/matrigel to construct and reflect the proliferation and apoptosis of 3D cells. It was confirmed that 3D cell viability detected by the MGIS platform is highly consistent with the standard live/dead staining. Furthermore, the accuracy of MGIS platform was demonstrated quantitatively using 3D lung cancer model and sophisticated drug sensitivity testing. In addition, the parameters of micro-groove impedance chip processing and measurement experiments were optimized in details. The results demonstrated that the MGIS and 3D cell-based biosensor and would be a promising platform to improve the efficiency and accuracy of cell-based anti-cancer drug screening in vitro.

Keywords: micro-groove impedance sensor, 3D cell-based biosensors, 3D cell viability, micro-electromechanical systems

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Authors: Bara M Yousef, Naresh B Raj, Nadiah W Arfah, Brightlin N Dhas

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Background: Executive function (EF) impairment is common in children with autism spectrum disorder (ASD). EF strategies are considered effective in improving the therapeutic outcomes of children with ASD. Aims: This study primarily aims to explore whether integrating EF strategies combined with regular occupational therapy intervention is more effective in improving daily life skills (DLS) and sensory integration/processing (SI/SP) skills than regular occupational therapy alone in children with ASD and secondarily aims to assess treatment outcomes on improving visual motor integration (VMI) skills. Procedures: A total of 92 children with ASD will be recruited and, following baseline assessments, randomly assigned to the treatment group (45-min once weekly individual occupational therapy plus EF strategies) and control group (45-min once weekly individual therapy sessions alone). Results and Outcomes: All children will be evaluated systematically by assessing SI/SP, DLS, and VMI, skills at baseline, 7 weeks, and 14 weeks of treatment. Data will be analyzed using ANCOVA and T-test. Conclusions and Implications: This single-blind, randomized controlled trial will provide empirical evidence for the effectiveness of EF strategies when combined with regular occupational therapy programs. Based on trial results, EF strategies could be recommended in multidisciplinary programs for children with ASD. Trial Registration: The trial has been registered in the clinicaltrail.gov for a registry, protocol ID: MRC-01-22-509 ClinicalTrials.gov Identifier: NCT05829577, registered 25th April 2023

Keywords: autism spectrum disorder, executive function strategies, daily life skills, sensory integration/processing, visual motor integration, occupational therapy, effectiveness

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Authors: Vipin Saini, Manish Kumar, Shailendra Bhatt, A. Pandurangan

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The aim of the present study was to fabricate a thermo sensitive gel containing Chlorpheniramine maleate (CPM) loaded nanoparticles following intranasal administration for effective treatment of allergic rhinitis. Chitosan based nanoparticles were prepared by precipitation method followed by the addition of developed NPs within the Poloxamer 407 and carbopol 934P based mucoadhesive thermo-reversible gel. Developed formulations were evaluated for Particle size, PDI, % entrapment efficiency and % cumulative drug permeation. NP3 formulation was found to be optimized on the basis of minimum particle size (143.9 nm), maximum entrapment efficiency (80.10±0.414 %) and highest drug permeation (90.92±0.531 %). The optimized formulation NP3 was then formulated into thermo reversible in situ gel. This intensifies the contact between nasal mucosa and the drug, increases and facilitates the drug absorption which results in increased bioavailability. G4 formulation was selected as the optimize on the basis of gelation ability and mucoadhesive strength. Histology was carried out to examine the damage caused by the optimized G4 formulation. Results revealed no visual signs of tissue damage thus indicated safe nasal delivery of nanoparticulate in situ gel formulation G4. Thus, intranasal CPM NP-loaded in situ gel was found to be a promising formulation for the treatment of allergic rhinitis.

Keywords: chitosan, nanoparticles, in situ gel, chlorpheniramine maleate, poloxamer 407

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Authors: Valerie Alexander, Amanda Gutierrez, Veronica Campbell, Dara Schwartz, B. Charles Tatum

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It has long been assumed that personality disorders (PD) originate in adolescence or early adulthood and that the maladaptive behaviors significantly attenuate over time. The Diagnostic and Statistical Manual of Mental Disorders-5 supports early onset of PD and views the pattern of behaviors as enduring and stable. The premise of this study is that PD may not always begin early in life, that behaviors may change over the lifespan, and that current treatment modalities may be beneficial in seniors. Self-injurious behaviors (SIB) exhibited earlier in life may, in older adults, be manifested in less overt high-risk behaviors but by refusal to take medication and get necessary medical treatment. Dialectical Behavioral Therapy is a well-known treatment modality for teaching emotional regulation and distress tolerance and thus reducing self-injurious behaviors yet very little has been studied about SIB and treatment in older adults. The population for this study was older adults, with a history of SIB, a PD, and depression and/or anxiety. Participants learned an adapted version of Dialectical Behavioral Therapy (DBT) as developed by DBT trained therapists. The results provided clinical potentials for the efficacy of DBT to reduce SIB, decrease depression and anxiety in the older adult population.

Keywords: anxiety, depression, dialectical behavioral therapy, personality disorders, self-harm behavior, treatment in older adults

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Authors: Victoria I. Michailova, Denitsa B. Momekova, Hristiana A. Velichkova, Evgeni H. Ivanov

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The aim of this work is to design and develop thermo-responsive nanosized drug delivery systems based on poly(N-isopropylacrylamide)-g-poly(ethylene oxide) (PNIPAM-g-PEO) double hydrophilic graft copolymers. The PNIPAM-g-PEO copolymers are able to self-assemble in water into nanoparticles above the LCST of the thermo-responsive PNIPAM backbone and to disassemble and rapidly release the entrapped drugs upon cooling. However, their drug delivery applications are often hindered by their low loading capacity as the drugs to be encapsulated do not dissolve in water. In order to overcome this limitation, here we applied a low-temperature procedure with ethanol as an alternative route to the formation and loading a model hydrophobic drug, Indomethacin (IMC), into PNIPAM-g-PEO nanoparticles. The rationale for this approach was that ethanol dissolves both IMC and the copolymer and its mixing with water may induce micellization of PNIPAM-g-PEO at temperatures lower than the LCST. The influence of the volume fraction of ethanol and the temperature on the aggregation characteristics of PNIPAM-g-PEO copolymers (2.7 mol% PEO) was investigated by means of DLS, TEM and rheological dynamic oscillatory tests. The studies showed rich phase behavior at T < LCST, incl. the formation of highly solvated 500-1000 nm complex structures, 30-70 nm micelles and polymersomes as well as giant polymersomes, as the fraction of added ethanol increased. We believe that the PNIPAM-g-PEO self-assembly is favored due to the different solvation of its constituting blocks in ethanol-water mixtures. The incorporation of IMC led to alteration of the physicochemical and morphological characteristics of the blank nanoparticles. In this case, only monodisperse polymersomes and micelles were observed in the solutions with an average diameter less than 65 nm and substantial drug loading (DLC ~117 – 146 wt%). Indomethacin release from the nanoparticles was responsive to temperature changes, being much faster at a temperature of 42oC compared to that of 37oC under otherwise the same conditions. The results obtained suggest that these PNIPAM-g-PEO nanoparticles could be potential in mild hyper-thermic delivery of nonsteroidal anti-inflammatory drugs.

Keywords: drug delivery, nanoparticles, poly(N-isopropylacryl amide)-g-poly(ethylene oxide), thermo-responsive

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Authors: Julia Wong, Hua Beng Lim, Cheryl Ho, Gin Jen Gwee, Rachel Tay

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In Singapore, a few hospitals and non-governmental social service agencies have been utilising animal-assisted therapy (AAT) in their practice in recent years, although the animals used (e.g., dogs, cats, and horses) and program modality may differ due to the different practice settings, client profiles, and intervention goals. This pilot study explores dog owners’ perceptions of AAT with a focus on examining the enablers and barriers towards volunteering with their dogs in AAT programs in Singapore. A qualitative, thematic analysis study was conducted using in-depth, semi-structured interviews with 16 dog owners. 3 of the dog owners had previous experience volunteering with their dogs serving elderly patients in a community hospital, while the rest of the dog owners had no previous experience volunteering with their dogs. The former group was recruited with the help of the hospital, while the latter group was recruited via word-of-mouth. Dog owners who had volunteering experiences in AAT program versus those who had none differed in their perceptions towards AAT. Dog owners who had volunteered with their dogs in an AAT program in a hospital felt that their volunteering experience were meaningful to patients and to themselves, as they were intrinsically motivated by the desire to serve the community. Those who had not volunteered were hesitant to volunteer with their dogs as they were not comfortable with strangers touching their dogs. They also felt that it would be a huge commitment in terms of time and money; most of them do not own a car as it is uneconomical, and pets are not allowed on Singapore’s public transport systems. This study is limited by its small sample size, and its findings are not generalisable. However, given that volunteers are an invaluable resource in healthcare settings, future studies can examine more stakeholders’ perceptions towards AAT.

Keywords: animal-assisted therapy, dog-assisted therapy, volunteers, complementary therapy

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Authors: Reihaneh Mahdavishahri, Dumayi Gutierrez

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Emotionally focused couple therapy (EFCT) is one of the most effective and evidence-based approaches to couple therapy. Yet, literature is scarce of its effective application with trans and non-binary couples. It is estimated that 1.4 million trans adults live in the United Stated, with about 40% of these individuals experiencing serious psychological distress within the past month. Trans and nonbinary adults are significantly likely to experience discrimination, harassment, family rejection, and relationship challenges throughout the course of their lives. As systemic therapists, applying an informed lens when working with trans and nonbinary couples can contribute to providing effective mental health care to these individuals. This paper aims to provide a comprehensive, intersectional, and culturally informed application of EFCT with trans and nonbinary couples. We will address the current literature on applications of EFCT with diverse couples, EFCT’s strengths and limitations on cultural humility, and the gaps within current systems of care for trans and nonbinary couples. We will then provide an adaptive application of EFCT to help trans, and nonbinary couples recover from potential attachment injuries in their relationships, intersecting gender minority stressors, and achieve healing and restoration in their interpersonal dynamics.

Keywords: attachment, culturally informed care, emotionally focused couple therapy, trans and nonbinary couples

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Authors: Sultana Razia

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The purpose of this study was to investigate the effect of early therapeutic intervention on children with an autism spectrum disorder. Participants were 140 children with autism spectrum disorder from Autism Corner in a selected rehabilitation center of Bangladesh. This study included children who are at aged of 18-month to 36-month and who were taking occupational therapy and speech and language therapy from the autism center. They were primarily screened using M-CHAT; however, children with other physical disabilities or medical conditions were excluded. 3-months interventions of 6 sessions per week are a minimum of 45-minutes long per session, one to one interaction followed by parent-led structured home-based therapy were provided. The results indicated that early intensive therapeutic intervention improves understanding, social skills and sensory skills. It can be concluded that therapeutic early intervention has a positive effect on diminishing symptoms of Autism Spectrum Disorder.

Keywords: autism, m-chat, reciprocal social behavior, CRP

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Authors: Zhen Ye, Maryam Zaroudi, Elizabeth Aisenbrey, Nicolynn E. Davis, Peng Gao

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Nanoparticles have been used as drug delivery systems in the treatment of life-threatening diseases for decades, but traditional formulation development methods are time consuming and labor intensive. Millipore Sigma has developed a platform¬¬– NanoFabTxTM¬¬– for rapid and reproducible formulation development and screening to ensure consistentnanoparticle characteristics. Reproducible and precise control of the development process for a range of nanoparticle formulations accelerates the introduction of novel formulations to the clinic.

Keywords: Bio platform, Formulation development, NanoFabTxTM, Drug delivery

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Authors: Marini Kristina Situmeang, Siti Hazar Sitorus, Mukhammad Fatkhullah, Arfan Fadli

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This study aims to identify and explain how forms of treatment and community action include parents who have children with mental retardation while undergoing behavioral therapy that leads to habituation processes. Based on observations made there is inappropriate treatment such as labeling that child mental retardation is considered ‘crazy’ by some people in Aceh Besar region. Reflecting on the phenomenon of discriminatory treatment, the existence of children with mental retardation should be realized in concrete actions that can encourage the development of cognitive abilities, language, motor, and social, one of them through behavioral. The purpose of this research is to find out and explain how the social practices of children with mental retardation when undergoing behavioral therapy that leads to habituation process. This study focuses on families or parents who have children with mental retardation and do therapy of behavioral therapy at home or at physiotherapy clinics in Aceh Besar. The research method is qualitative with case study approach. Data collection techniques are conducted with in-depth interviews and Focus Group Discussion (FGD). The results showed that habituation process which is conducted by parents at home and in fisotherapy clinic have a positive effect on the development of children behavior of mental retardation, especially when dealing with the environment of the community around the residence. Habituation processes conducted through behavioral therapy practices are influenced by Habitus (Gestational and childcare at therapy) and Reinforcement (in this case family and social support). Habituation process is done in the form of habituation, the creation of the situation, and strengthening the character. For example, when a child's mental retardation commits a wrong act (disgraceful or inappropriate behavior) then the child gets punishment in accordance with the form of punishment in a normal child generally, and when he performs a good deed, then he is given a prize such as praise or a thing he likes. Through some of these actions, the child with mental retardation can behave in accordance with the character formed and expected by the community. The process of habituation done by parents accompanied by continuous support of physiotherapy can be one of the alternative booster of cognitive and social development of children mental retardation to then out of the ‘crazy’ label that has been given.

Keywords: behaviour therapy, habituation, habitus, mental retardation

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Authors: Suhas Pednekar, Prashant Chavan, Ramesh Chaughule, Deepak Patkar

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Iron oxide (Fe3O4) magnetic nanoparticles (MNPs) are one of the most attractive nanomaterials for various biomedical applications. An important potential medical application of polymer-coated iron oxide nanoparticles (NPs) is as imaging agents. Composition, size, morphology and surface chemistry of these nanoparticles can now be tailored by various processes to not only improve magnetic properties but also affect the behavior of nanoparticles in vivo. MNPs are being actively investigated as the next generation of magnetic resonance imaging (MRI) contrast agents. Also, there is considerable interest in developing magnetic nanoparticles and their surface modifications with therapeutic agents. Our study involves the synthesis of biocompatible cancer drug coated with iron oxide nanoparticles and to evaluate their efficacy as MRI contrast agents. A simple and rapid microwave method to prepare Fe3O4 nanoparticles has been developed. The drug was successfully conjugated to the Fe3O4 nanoparticles which can be used for various applications. The relaxivity R2 (reciprocal of the spin-spin relaxation time T2) is an important factor to determine the efficacy of Fe nanoparticles as contrast agents for MRI experiments. R2 values of the coated magnetic nanoparticles were also measured using MRI technique and the results showed that R2 of the Fe complex consisting of Fe3O4, polymer and drug was higher than that of bare Fe nanoparticles and polymer coated nanoparticles. This is due to the increase in hydrodynamic sizes of Fe NPs. The results with various amounts of iron molar concentrations are also discussed. Using MRI, it is seen that the R2 relaxivity increases linearly with increase in concentration of Fe NPs in water.

Keywords: cancer drug, hydrodynamic size, magnetic nanoparticles, MRI

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Authors: Gholam Reza Mirzaei

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This research aimed to investigate the effectiveness of acceptance and commitment therapy (ACT) in reducing corona disease anxiety in the staff working at Shahid Beheshti Hospital of Shiraz. The current research was a quasi-experimental study having pre-test and post-test with two experimental and control groups. The statistical population of the research included all the staff of Shahid Beheshti Hospital of Shiraz in 2021. From among the statistical population, 30 participants (N =15 in the experimental group and N =15 in the control group) were selected by available sampling. The materials used in the study comprised the Cognitive Emotion Regulation Questionnaire (CERQ) and Corona Disease Anxiety Scale (CDAS). Following data collection, the participants’ scores were analyzed using SPSS 20 at both descriptive (mean and standard deviation) and inferential (analysis of covariance) levels. The results of the analysis of covariance (ANCOVA) showed that acceptance and commitment therapy (ACT) is effective in reducing Corona disease anxiety (mental and physical symptoms) in the staff working at Shahid Beheshti Hospital of Shiraz. The effectiveness of acceptance and commitment therapy (ACT) on reducing mental symptoms was 25.5% and on physical symptoms was 13.8%. The mean scores of the experimental group in the sub-scales of Corona disease anxiety (mental and physical symptoms) in the post-test were lower than the mean scores of the control group.

Keywords: acceptance and commitment therapy, corona disease anxiety, hospital staff, Shiraz

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Authors: Nichole Haag, Kimberly Velk, Tyler McCune, Chun Wu

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Methicillin/multiple-resistant Staphylococcus aureus (MRSA) are infectious bacteria that are resistant to common antibiotics. A previous in silico study in our group has identified a hypothetical protein SAV1226 as one of the potential drug targets. In this study, we reported the bioinformatics characterization, as well as cloning, expression, purification and kinetic assays of hypothetical protein SAV1226 from methicillin/vancomycin-resistant Staphylococcus aureus Mu50 strain. MALDI-TOF/MS analysis revealed a low degree of structural similarity with known proteins. Kinetic assays demonstrated that hypothetical protein SAV1226 is neither a domain of an ATP dependent dihydroxyacetone kinase nor of a phosphotransferase system (PTS) dihydroxyacetone kinase, suggesting that the function of hypothetical protein SAV1226 might be misannotated on public databases such as UniProt and InterProScan 5.

Keywords: Methicillin-resistant Staphylococcus aureus, dihydroxyacetone kinase, essential genes, drug target, phosphoryl group donor

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Authors: Papon Thamvasupong, Kwanchanok Viravaidya-Pasuwat

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Osteoarthritis affects a lot of people worldwide. Local injection of glucosamine is one of the alternative treatment methods to replenish the natural lubrication of cartilage. However, multiple injections can potentially lead to possible bacterial infection. Therefore, a drug delivery system is desired to reduce the frequencies of injections. A hydrogel is one of the delivery systems that can control the release of drugs. Thermo-reversible hydrogels can be beneficial to the drug delivery system especially in the local injection route because this formulation can change from liquid to gel after getting into human body. Once the gel is in the body, it will slowly release the drug in a controlled manner. In this study, various formulations of Pluronic-based hydrogels were synthesized for the controlled release of glucosamine. One of the challenges of the Pluronic controlled release system is its fast dissolution rate. To overcome this problem, alginate and calcium sulfate (CaSO₄) were added to the polymer solution. The characteristics of the hydrogels were investigated including the gelation temperature, gelation time, hydrogel dissolution and glucosamine release mechanism. Finally, a mathematical model of glucosamine release from Pluronic-alginate-hyaluronic acid hydrogel was developed. Our results have shown that crosslinking Pluronic gel with alginate did not significantly extend the dissolution rate of the gel. Moreover, the gel dissolution profiles and the glucosamine release mechanisms were best described using the zeroth-order kinetic model, indicating that the release of glucosamine was primarily governed by the gel dissolution.

Keywords: controlled release, drug delivery system, glucosamine, pluronic, thermoreversible hydrogel

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Authors: Abhay Asthana, Shally Toshkhani, Gyati Shilakari

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The present research was aimed to develop a biodegradable dermal patch formulation for wound healing in a novel, sustained and systematic manner. The goal is to reduce the frequency of dressings with improved drug delivery and thereby enhance therapeutic performance. In present study optimized formulation was designed using component polymers and excipients (e.g. Hydroxypropyl methyl cellulose, Ethylcellulose, and Gelatin) to impart significant folding endurance, elasticity and strength. Gelatin was used to get a mixture using ethylene glycol. Chitosan dissolved in suitable medium was mixed with stirring to gelatin mixture. With continued stirring to the mixture Curcumin was added in optimized ratio to get homogeneous dispersion. Polymers were dispersed with stirring in final formulation. The mixture was sonicated casted to get the film form. All steps were carried out under under strict aseptic conditions. The final formulation was a thin uniformly smooth textured film with dark brown-yellow color. The film was found to have folding endurance was around 20 to 21 times without a crack in an optimized formulation at RT (23C). The drug content was in range 96 to 102% and it passed the content uniform test. The final moisture content of the optimized formulation film was NMT 9.0%. The films passed stability study conducted at refrigerated conditions (4±0.2C) and at room temperature (23 ± 2C) for 30 days. Further, the drug content and texture remained undisturbed with stability study conducted at RT 23±2C for 45 and 90 days. Percentage cumulative drug release was found to be 80% in 12 h and matched the biodegradation rate as drug release with correlation factor R2 > 0.9. The film based formulation developed shows promising results in terms of stability and release profiles.

Keywords: biodegradable, patch, bioactive, polymer

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Authors: Sema Şenoğlu, Sevgi Karakuş

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Hydrazone scaffold is important to design new drug groups and is found to possess numerous uses in pharmaceutical chemistry. Besides, hydrazone derivatives are also known for biological activities such as anticancer, antimicrobial, antiviral, and antifungal. Hydrazone derivatives are promising anticancer agents because they inhibit cancer proliferation and induce apoptosis. Human carbonic anhydrase IX has a high potential to be an antiproliferative drug target, and targeting this protein is also important for obtaining potential anticancer inhibitors. The protein construct was retrieved as a PDB file from the RCSB protein database. This binding interaction of proteins and ligands was performed using Discovery Studio Visualizer. In vitro inhibitory activity of hydrazone derivatives was tested against enzyme carbonic anhydrase IX on the PyRx programme. Most of these molecules showed remarkable human carbonic anhydrase IX inhibitory activity compared to the acetazolamide. As a result, these compounds appear to be a potential target in drug design against human carbonic anhydrase IX.

Keywords: cancer, carbonic anhydrase IX enzyme, docking, hydrazone

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Authors: Junie B. Billones, Maria Constancia O. Carrillo, Voltaire G. Organo, Stephani Joy Y. Macalino, Inno A. Emnacen, Jamie Bernadette A. Sy

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One of the major interferences in the Philippines’ tuberculosis control program is the widespread prevalence of Mtb strains that are resistant to known drugs, such as the MDR-TB (Multi Drug Resistant Tuberculosis) and XDR-TB (Extensively Drug Resistant Tuberculosis). Therefore, there is a pressing need to search for novel Mtb drug targets in order to be able to combat these drug resistant strains. The enzyme 7,8-diaminopelargonic acid aminotransferase enzyme, or more commonly known as BioA, is one such ideal target, as it is known that humans do not possess this enzyme. BioA primarily plays a key role in Mtb’s lipid biosynthesis pathway; more specifically in the synthesis of the enzyme cofactor biotin. In this study, structure-based pharmacophore screening, docking, and ADMET evaluation of compounds obtained from the DrugBank chemical database were performed against the MtbBioA enzyme. Results of the screening, docking, ADMET, and TOPKAT calculations revealed that out of the 6,516 compounds in the library, only 7 compounds indicated more favorable binding energies as compared to the enzyme’s known inhibitor, amiclenomycin (ACM), as well as good solubility and toxicity properties. Moreover, out of these 7 compounds, Molecule 6 exhibited the best solubility and toxicity properties. In the future, these lead compounds may then be subjected to bioactivity assays in vitro or in vivo for further evaluation of its therapeutic efficacy.

Keywords: 7, 8-diaminopelargonic acid aminotransferase, BioA, pharmacophore, molecular docking, ADMET, TOPKAT

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Authors: John Hang Leung, Shyh-Yau Wang, Hei-Tung Yip, Fion, Ho Tsung-chin, Agnes LF Chan

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Objectives: Platinum-resistant ovarian cancer has a short overall survival of 9–12 months and limited treatment options. The combination of immunotherapy and targeted therapy appears to be a promising treatment option for patients with ovarian cancer, particularly to patients with platinum-resistant recurrent ovarian cancer (PRrOC). However, there are no direct head-to-head clinical trials comparing their efficacy and toxicity. We, therefore, used a network to directly and indirectly compare seven newer immunotherapies or targeted therapies combined with chemotherapy in platinum-resistant relapsed ovarian cancer, including antibody-drug conjugates, PD-1 (Programmed death-1) and PD-L1 (Programmed death-ligand 1), PARP (Poly ADP-ribose polymerase) inhibitors, TKIs (Tyrosine kinase inhibitors), and antiangiogenic agents. Methods: We searched PubMed (Public/Publisher MEDLINE), EMBASE (Excerpta Medica Database), and the Cochrane Library electronic databases for phase II and III trials involving PRrOC patients treated with immunotherapy or targeted therapy plus chemotherapy. The quality of included trials was assessed using the GRADE method. The primary outcomes compared were progression-free survival, the secondary outcomes were overall survival and safety. Results: Seven randomized controlled trials involving a total of 2058 PRrOC patients were included in this analysis. Bevacizumab plus chemotherapy showed statistically significant differences in PFS (Progression-free survival) but not OS (Overall survival) for all interested targets and immunotherapy regimens; however, according to the heatmap analysis, bevacizumab plus chemotherapy had a statistically significant risk of ≥grade 3 SAEs (Severe adverse effects), particularly hematological severe adverse events (neutropenia, anemia, leukopenia, and thrombocytopenia). Conclusions: Bevacizumab plus chemotherapy resulted in better PFS as compared with all interested regimens for the treatment of PRrOC. However, statistical differences in SAEs as bevacizumab plus chemotherapy is associated with a greater risk for hematological SAE.

Keywords: platinum-resistant recurrent ovarian cancer, network meta-analysis, immune checkpoint inhibitors, target therapy, antiangiogenic agents

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Authors: Canan Gunay Yazici, Zubeyir Sarı, Devrim Tarakci

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Background: Hippotherapy considered as global techniques used in rehabilitation of children with cerebral palsy as it improved gait pattern, balance, postural control, balance and gross motor skills development but it encounters some problems (such as the excess of the cost of horses' care, nutrition, housing). Hippotherapy simulator is being developed in recent years to overcome these problems. These devices aim to create the effects of hippotherapy made with a real horse on patients by simulating the movements of a real horse. Objectives: To evaluate the efficacy of hippotherapy simulator on gross motor functions, sitting postural control and dynamic balance of children with cerebral palsy (CP). Methods: Fourteen children with CP, aged 6–15 years, seven with a diagnosis of spastic hemiplegia, five of diplegia, two of triplegia, Gross Motor Function Classification System level I-III. The Horse Riding Simulator (HRS), including four-speed program (warm-up, level 1-2-3), was used for hippotherapy simulator. Firstly, each child received Neurodevelopmental Therapy (NDT; 45min twice weekly eight weeks). Subsequently, the same children completed HRS+NDT (30min and 15min respectively, twice weekly eight weeks). Children were assessed pre-treatment, at the end of 8th and 16th week. Gross motor function, sitting postural control, dynamic sitting and standing balance were evaluated by Gross Motor Function Measure-88 (GMFM-88, Dimension B, D, E and Total Score), Trunk Impairment Scale (TIS), Pedalo® Sensamove Balance Test and Pediatric Balance Scale (PBS) respectively. Unit of Scientific Research Project of Marmara University supported our study. Results: All measured variables were a significant increase compared to baseline values after both intervention (NDT and HRS+NDT), except for dynamic sitting balance evaluated by Pedalo®. Especially HRS+NDT, increase in the measured variables was considerably higher than NDT. After NDT, the Total scores of GMFM-88 (mean baseline 62,2 ± 23,5; mean NDT: 66,6 ± 22,2; p < 0,05), TIS (10,4 ± 3,4; 12,1 ± 3; p < 0,05), PBS (37,4 ± 14,6; 39,6 ± 12,9; p < 0,05), Pedalo® sitting (91,2 ± 6,7; 92,3 ± 5,2; p > 0,05) and Pedalo® standing balance points (80,2 ± 10,8; 82,5 ± 11,5; p < 0,05) increased by 7,1%, 2%, 3,9%, 5,2% and 6 % respectively. After HRS+NDT treatment, the total scores of GMFM-88 (mean baseline: 62,2 ± 23,5; mean HRS+NDT: 71,6 ± 21,4; p < 0,05), TIS (10,4 ± 3,4; 15,6 ± 2,9; p < 0,05), PBS (37,4 ± 14,6; 42,5 ± 12; p < 0,05), Pedalo® sitting (91,2 ± 6,7; 93,8 ± 3,7; p > 0,05) and standing balance points (80,2 ± 10,8; 86,2 ± 5,6; p < 0,05) increased by 15,2%, 6%, 7,3%, 6,4%, and 11,9%, respectively, compared to the initial values. Conclusion: Neurodevelopmental therapy provided significant improvements in gross motor functions, sitting postural control, sitting and standing balance of children with CP. When the hippotherapy simulator added to the treatment program, it was observed that these functions were further developed (especially with gross motor functions and dynamic balance). As a result, this pilot study showed that the hippotherapy simulator could be a useful alternative to neurodevelopmental therapy for the improvement of gross motor function, sitting postural control and dynamic balance of children with CP.

Keywords: balance, cerebral palsy, hippotherapy, rehabilitation

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Authors: Mikhail S. Zastrozhin, Valery V. Smirnov, Dmitry A. Sychev, Ludmila M. Savchenko, Evgeny A. Bryun, Mark O. Nechaev

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Cytochrome P-450 isoenzyme 3A4 takes part in the biotransformation of medical drugs. The activity of CYP isoenzymes depends on genetic (polymorphisms of genes which encoded it) and phenotypic factors (a kind of food, a concomitant drug therapy). The aim of the study was to evaluate a carbamazepine effect on the CYP3A4 activity in patients with alcohol addiction. The study included 25 men with alcohol dependence, who received haloperidol during the exacerbation of the addiction. CYP3A4 activity was assessed by urinary 6-beta-hydroxycortisol/cortisol ratios measured by high performance liquid chromatography with mass spectrometry. The study modeled a graph and an equation of the logarithmic regression, that reflects the dependence of CYP3A4 activity on a dose of carbamazepine: y = 5,5 * 9,1 * 10-5 * x2. The study statistically significant demonstrates the effect of carbamazepine on CYP2D6 isozyme activity in patients with alcohol addiction.

Keywords: CYP3A4, biotransformation, carbamazepine, alcohol abuse

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Authors: Nawal A. Abu-Shady, Ibrahim M. I. Hamoda, Ahmed R. Z. Baghdadi, Mohammed K. Mohamed

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Background: The aim of this work was to investigate the efficacy of Transcranial Magnetic Therapy (TMT) on balance in hemiparetic stroke patients. It was conducted in outpatient clinic and in BIODEX balance system lab in Faculty of Physical Therapy, Cairo University. Subjects and Methods: Thirty hemiparetic stroke patients from both sexes represent the sample of this study. The patients' ages ranged from 45 to 55 years. They were assigned randomly into two equal groups; the study group (GA) and the control group (GB). control group treated by selected therapeutic physical therapy program. GA treated by the same program of treatment as the GB in addition to TMT. The duration of treatment was six weeks, three times weekly.day after day. The different aspects of dynamic balance (overall stability, anteroposterior stability and mediolateral stability indices) were assessed pre and post treatment objectively by Biodex balance system and clinically by Short Form of Berg Balance Scale (SFBBS) in both groups. Results: Comparison of each variable pre and post treatment in each group revealed a significant improvement in all different parameters in both groups ( p < 0.01), however comparison between post results revealed that the GA showed a high significant improvement higher than the GB in all different variables.

Keywords: stroke, TMT, SFBBS, biodex balance system

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Authors: Temesgen Geremew

Abstract:

Functionalized nanoparticles have emerged as a revolutionary class of materials with immense potential in various biomedical applications. These engineered nanoparticles possess unique properties tailored to interact with biological systems, offering unprecedented opportunities in drug delivery, imaging, diagnostics, and therapy. This research delves into the design, synthesis, and characterization of functionalized nanoparticles for targeted biomedical applications. The primary focus lies on developing nanoparticles with precisely controlled size, surface chemistry, and biocompatibility for specific medical purposes. The research will also explore the crucial interaction of these nanoparticles with biological systems, encompassing cellular uptake, biodistribution, and potential toxicity evaluation. The successful development of functionalized nanoparticles holds the promise to revolutionize various aspects of healthcare. This research aspires to contribute significantly to this advancement by providing valuable insights into the design and application of these versatile materials within the ever-evolving field of biomedicine.

Keywords: nanoparticles, biomedicals, cancer, biocompatibility

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