Combined Therapy Approach Research Articles

Dual targeting of HSP90 and BCL-2 in breast cancer cells using inhibitors BIIB021 and ABT-263.

The incidence of breast cancer has been increasing in recent years, and monotherapy approaches are not sufficient alone in the treatment of breast cancer. In the combined therapy approach, combining two or three different agents in lower doses can mitigate the side effects on living cells and tissues caused by high doses of chemical agents used alone. ABT-263 (navitoclax), a clinically tested Bcl-2 family protein inhibitor, has shown limited success in clinical trials due to the development of resistance to monotherapy in breast cancer cells. This resistance shows that monotherapy approaches are inadequate and more effective treatment strategies are needed. It is the ability of HSP90 inhibitors to destabilize many oncoproteins that are critical for the survival of cancer cells. This study aimed to examine the anticancer activity of the combination of ABT-263 with BIIB021, a new generation HSP90 inhibitor, on two widely used breast cancer cell lines: MCF-7 (ER-positive) and MDA-MB-231 (triple-negative breast cancer, TNBC). These cell lines were selected to represent distinct breast cancer subtypes with different molecular characteristics and clinical behaviors. Single and combined cytotoxic effects of this agents on MCF-7 and MDA-MB-231 breast cancer cell lines were determined using the MTT cell viability test. The combined use of these two agents showed a synergistic effect, and this effect was assigned using the Chou and Talalay method. mRNA and protein levels of apoptosis-related genes Bax, Bcl-2, Casp9, and Heat Shock Proteins HSP27, HSP70, and HSP90 were analyzed using Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Western Blotting, respectively. The cytotoxicity analysis, combined with the application of the Chou-Talalay method, demonstrated that the BIIB021 and ABT-263 combination exhibited significantly greater anticancer activity compared to the individual effects of either BIIB021 or ABT-263 in breast cancer cell lines. The analysis of mRNA and protein levels indicated that the BIIB021+ABT-263 combination may have triggered the intrinsic apoptotic pathway in breast cancer cells. This study showed thatco-administration of ABT-263 and BIIB021 agents exhibited synergistic cytotoxic effects and increased the expression of apoptosis-related genes in breast cancer cell lines.

Assess the efficacy of the combination of sports massage with heat therapy in improving range of motion in patients with shoulder pain?

Background and Study Aim. This study aims to assess the efficacy of combining sports massage and heat therapy in enhancing joint range of motion among patients experiencing shoulder pain. Shoulder pain often coincides with restricted range of motion, impacting daily activities and overall quality of life. Sports massage is recognized for its ability to alleviate muscle tension and enhance blood circulation, while heat therapy is known to decrease muscle stiffness and enhance tissue elasticity. The integration of these two therapies is anticipated to offer synergistic advantages in addressing shoulder pain issues and improving joint flexibility. Material and Methods. The research design employed in this study is pre-experimental, utilizing a one-group pretest and posttest approach. The intervention involved administering a regular combination of sports massage and heat therapy to a group of patients with shoulder pain. Joint range of motion was assessed before and after the intervention using a pretest-posttest design. Statistical analyses, including t-tests and significance tests, were conducted to evaluate the difference between the mean pretest and posttest values. Results. The findings revealed a notable increase in the mean posttest measurements compared to the pretest values. Moreover, the significance test results indicated a significant effect (0.001 < 0.05), highlighting the effectiveness of combining sports massage and heat therapy in augmenting joint range of motion among patients with shoulder pain. Conclusion. These results strongly support the implementation of the combined therapy approach in shoulder pain rehabilitation to address limitations in joint range of motion. This study contributes to the scientific comprehension of the synergistic benefits associated with both therapies and lays the groundwork for refining treatment guidelines for individuals with similar conditions.

The effectiveness of olfactory training for chronic olfactory disorder following COVID-19: a systematic review.

Chronic olfactory disorders are some of the most frequent post-COVID-19 presentations. Olfactory training (OT) is currently the most popular method used for treating post-viral olfactory dysfunction (PVOD). We evaluated the effect of olfactory training on the chronic olfactory disorders of patients infected with COVID-19. A systematic literature search was performed per PRISMA guidelines in PubMed, Scopus, Web of Science, EBSCOhost, and the Cochrane Library. Only patients with chronic olfactory disorders of 30 days or more were included. The primary outcome was the olfactory score at the end of follow-up. In all studies, improvement was defined as a positive change over time in the results of objective psychophysical olfactory tests. The most commonly used test was the Sniffin' Sticks. Typically, outcome measures involved comparing the mean olfactory scores. In the Sniffin' Sticks test, an improvement was also indicated by a change of 5.5 points or more in the Threshold, Discrimination, and Identification scores. Fourteen studies (1.596 participants) were included in this review. Among the included studies, up to 10 were RCTs. Nine studies assessed the combined effects of adjuvant therapy and olfactory training, while five studies assessed only OT. In our assessment, olfactory training alone produces significant improvements in chronic olfactory dysfunctions. However, a combined therapy approach is essential to achieve more effective outcomes. Integrating olfactory training with adjuvants like CoUltraPEALut, Cerebrolysin, and oral Vitamin A has demonstrated substantial benefits in enhancing post-COVID-19 olfactory function. Strict adherence to the OT protocol and extending the duration of OT to 3 months or more significantly enhance treatment outcomes.

REVITALIZING CERVICAL HEALTH: A CASE STUDY ON THE EFFICACY OF APAMARGA KSHARA PRATISARANA WITH TRIPHALA KWATH PRAKSHALANA AND JATYADI TAIL PICHU

Cervical ectropion or erosion is a prevalent gynaecological condition characterised by replacing the natural squamous epithelium with columnar epithelium on the ectocervix. In Ayurveda, this condition is correlated with Karnini Yonivyapad, which results from local dosha disturbance in the reproductive tract. Acharyas have rec-ommended that Bahira Parimarjana Chikitsa address this dosha imbalance using a therapeutic approach focus-ing on external cleansing and treatment. The pathogenesis of Karnini Yonivyapad suggests that Kaphahara Chikitsa, involving Kshara as a local application, is effective due to its properties of being Katu, Ushna, Tik-shna, Pachana, Vilayana, Shodhana, Ropana, Shoshana, Stambhana, Lekhana, and Kaphanashaka. While con-ventional treatments may alleviate symptoms, they often fail to address the underlying issue. This study demon-strates that a combined therapy approach can effectively cure cervical erosion by utilising Apamarga Kshara Pratisarana with Triphala Kwath Prakshalana and Jatyadi Tail Pichu.

Hyperthermia Intensifies α-Mangostin and Synthetic Xanthones' Antimalignancy Properties.

In order to improve naturally occurring xanthones' anticancer properties, chemical synthesis is proposed. In this study, from eight novel xanthone derivatives coupled to morpholine or aminoalkyl morpholine, only the two most active ones were chosen. For additional enhancement of the anticancer activity of our tested compounds, we combined chemotherapy with hyperthermia in the range of 39-41 °C, from which the mild conditions of 39 °C were the most influencing. This approach had a profound impact on the anticancer properties of the tested compounds. TOV-21G and SC-OV-3 ovarian cell line motility and metastasis behavior were tested in native and hyperthermia conditions, indicating decreased wound healing properties and clonogenic activity. Similarly, the expression of genes involved in metastasis was hampered. The expression of heat shock proteins involved in cancer progression (Hsc70, HSP90A, and HSP90B) was significantly influenced by xanthone derivatives. Chemotherapy in mild hyperthermia conditions had also an impact on decreasing mitochondria potential, visualized with JC-1. Synthetic xanthone ring modifications may increase the anticancer activity of the obtained substances. Additional improvement of their activity can be achieved by applying mild hyperthermia conditions. Further development of a combined anticancer therapy approach may result in increasing currently known chemotherapeutics, resulting in a greater recovery rate and diminishment of the cytotoxicity of drugs.

The combined use of statin and rapamycin treatments synergistically inhibit the proliferation of B cell Lymphoma

Abstract Sterol Regulatory Element-Binding Protein (SREBP) signaling plays a crucial role in maintaining sterol homeostasis during B cell activation and the proliferation of germinal center B cells. It is unclear whether this pathway can be targeted to effectively treat B cell lymphoma. We discovered that inhibiting SREBP signaling or its downstream target 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) using Fatostatin or Simvastatin effectively restrains the proliferation of B cell lymphoma cells. However, B cell lymphoma cells activate the mTORC1-pS6 pathway in response to statin treatment, suggesting a possible mechanism to counteract statin-induced cell cycle arrest. Combining statin treatment with the mTOR inhibitor rapamycin demonstrates a synergistic effect in inhibiting B cell lymphoma proliferation, impeding cell cycle progression, and regulating sterol production. These findings emphasize the potential of a combined therapy approach targeting both SREBP and mTORC1 as a treatment strategy for B cell lymphoma.

Cognitive Behavioral Therapy Factors Related to Outcomes in Depression Among Youth with HIV.

This is a secondary analysis of a multi-site, cluster (site) randomized trial of the efficacy of a combined Health and Wellness Cognitive Behavior Therapy (H&W CBT) and medication management approach for depression in youth with HIV (YWH) compared to standard care. In this study, we explored the association between H&W CBT factors and depression outcomes after 24 weeks of treatment to discover treatment elements associated with symptom reduction. Participants (12-24 years of age) were YWH in the United States (US) diagnosed with moderate to severe depression [Quick Inventory of Depressive Symptomatology (QIDS), Clinician-Rated score ≥ 11]. Thirteen US sites were randomly assigned to either the combination treatment approach or standard care. For site-level analyses, site-specific summary scores were used to account for the within site correlation. The number of depressive symptoms [QIDS-Self Reported (QIDS-SR) score] after 24 weeks of H&W CBT was significantly negatively correlated with the mean total session duration (ρ = - 0.94), the total homework assigned (ρ = - 0.83), the total number of practice modules used (ρ = - 0.83), and the mean total booster sessions given (ρ = - 0.82). Specific elements of the H&W CBT (e.g., dose, assignment of homework, greater skills practice, and use of booster sessions) were associated with improvement of depression outcomes in YWH. A focus on these elements in treatment may improve symptom reduction for YWH with depression.

Lentiviral expression of wild-type LAMA3A restores cell adhesion in airway basal cells from children with epidermolysis bullosa

The hallmark of epidermolysis bullosa (EB) is fragile attachment of epithelia due to genetic variants in cell adhesion genes. We describe 16 EB patients treated in the Ear, Nose and Throat department of a tertiary pediatric hospital linked to the United Kingdom’s National EB unit between 1992 and 2023. Patients suffered a high degree of morbidity and mortality from laryngotracheal stenosis. Variants in laminin subunit alpha-3 (LAMA3) were found in 10/15 patients where genotype was available. LAMA3 encodes a subunit of the laminin-332 heterotrimeric extracellular matrix protein complex and is expressed by airway epithelial basal stem cells. We investigated the benefit of restoring wildtype LAMA3 expression in primary EB patient-derived basal cell cultures. EB basal cells demonstrated weak adhesion to cell culture substrates, but could otherwise be expanded similarly to non-EB basal cells. In vitro lentiviral overexpression of LAMA3A in EB basal cells enabled them to differentiate in air-liquid interface cultures, producing cilia with normal ciliary beat frequency. Moreover, transduction restored cell adhesion to levels comparable to a non-EB donor culture. These data provide proof-of-concept for a combined cell and gene therapy approach to treat airway disease in LAMA3-affected EB.

Co-treatment with bone marrow-derived mesenchymal stem cells and curcumin improved angiogenesis in myocardium in a rat model of MI.

The cardioprotective properties of mesenchymal stem cells and the therapeutic potential of curcumin (CUR) have been explored. Combining these approaches may enhance stem cell effectiveness and expedite healing. This study aimed to investigate the synergistic effects of co-treating bone marrow mesenchymal stem cells (BMSCs) with curcumin on vascular endothelial growth factor (VEGF) levels, in a rat model of myocardial ischemia (MI). Sixty-five male rats were divided into four groups: G1 (healthy control), G2 (MI induced by isoproterenol hydrochloride), G3 (treated with BMSCs), and G4 (co-treated with curcumin and BMSCs). Blood and tissue samples were collected at specific time points (day 1, 7, 15 and 21) after MI induction. Serum levels of lactate dehydrogenase (LDH), creatine kinase (CK), cardiac troponin I (cTnI), aspartate aminotransferase (AST), CK-MB and VEGF were measured. VEGF mRNA and protein expression were evaluated using RT-qPCR and Western blot techniques. Histopathological assessments were performed using H&E staining and CD31 immunofluorescence staining. VEGF expression significantly increased on days 7 and 15 in the CUR-BMSCs group, peaking on day 7. Western blot analysis confirmed elevated VEGF protein expression on days 7 and 15 post-MI. ELISA results demonstrated increased serum VEGF levels on days 7 and 15, reaching the highest level on day 7 in CUR-BMSCs-treated animals. Treated groups showed lower levels of LDH, AST, CK, CK-MB and cTnI compared to the untreated MI group. H&E staining revealed improved myocardial structure, increased formation of new capillaries, in both treatment groups compared to the MI group. Combining curcumin with BMSCs promotes angiogenesis in the infarcted myocardium after 15days of MI induction. These findings suggest the potential of this combined therapy approach for enhancing cardiac healing and recovery.

Combined treatment with allogeneic Epstein–Barr- and human polyomavirus 1 specific T-cells in progressive multifocal leukoencephalopathy and EBV infection: a case report

Opportunistic viral infections in individuals with severe immunodeficiency can lead to fatal conditions such as progressive multifocal leukoencephalopathy (PML), for which treatment options are limited. These infections pose significant risks, especially when co-infections with other viruses occur. We describe a combined therapy approach using directly isolated allogeneic Human Polyomavirus 1 (also known as BKV) and Epstein–Barr virus (EBV) specific cytotoxic T-cells for the treatment of PML in conjunction with identified EBV in the cerebrospinal fluid (CSF) of a male patient infected with human immunodeficiency virus (HIV). A 53-year-old HIV-positive male, recently diagnosed with PML, presented with rapidly worsening symptoms, including ataxia, tetraparesis, dysarthria, and dysphagia, leading to respiratory failure. The patient developed PML even after commencing highly active antiretroviral therapy (HAART) 3 months prior. Brain magnetic resonance imaging (MRI) revealed multifocal demyelination lesions involving the posterior fossa and right thalamus suggestive of PML. In addition to the detection of human polyomavirus 2 (also known as JCV), analysis of CSF showed positive results for EBV deoxyribonucleic acid (DNA). His neurological condition markedly deteriorated over the following 2 months. Based on MRI, there was no evidence of Immune Reconstitution Inflammatory Syndrome contributing to this decline. The patient did not have endogenous virus-specific T-cells. We initiated an allogeneic, partially human leukocyte antigen-matched transfer of EBV and utilizing the cross-reactivity between BKV and JCV–BKV specific T-cells. This intervention led to notable neurological improvement and partial resolution of the MRI lesions within 6 weeks. Our case of a patient with acquired immune deficiency syndrome demonstrates that PML and concurrent EBV co-infection can still occur despite undergoing HAART treatment. This innovative experimental therapy, involving a combination of virus-specific T-cells, was demonstrated to be an effective treatment option in this patient.

Inflammatory myofibroblastic tumor from molecular diagnostics to current treatment.

Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm with intermediate malignancy characterized by a propensity for recurrence but a low metastatic rate. Diagnostic challenges arise from the diverse pathological presentation, variable symptomatology, and lack of different imaging features. However, IMT is identified by the fusion of the anaplastic lymphoma kinase (ALK) gene, which is present in approximately 70% of cases, with various fusion partners, including ran-binding protein 2 (RANBP2), which allows confirmation of the diagnosis. While surgery is the preferred approach for localized tumors, the optimal long-term treatment for advanced or metastatic disease is difficult to define. Targeted therapies are crucial for achieving sustained response to treatment within the context of genetic alteration in IMT. Crizotinib, an ALK tyrosine kinase inhibitor (TKI), was officially approved by the US Food and Drug Administration (FDA) in 2020 to treat IMT with ALK rearrangement. However, most patients face resistance and disease progression, requiring consideration of sequential treatments. Combining radiotherapy with targeted therapy appears to be beneficial in this indication. Early promising results have also been achieved with immunotherapy, indicating potential for combined therapy approaches. However, defined recommendations are still lacking. This review analyzes the available research on IMT, including genetic disorders and their impact on the course of the disease, data on the latest targeted therapy regimens and the possibility of developing immunotherapy in this indication, as well as summarizing general knowledge about prognostic and predictive factors, also in terms of resistance to systemic therapy.

Assessment of oropharyngeal respiratory volume and sleep apnoea scores using peripheral arterial tonometry may improve diagnosis and treatment planning of combined dysgnathia therapy approaches.

Increased daytime sleepiness is a frequently reported symptom in patients with pronounced dysgnathia. This study investigated possible correlations using home peripheral arterial tonometry (PAT) and oropharyngeal airway volume determination in patients with dysgnathia and daytime sleepiness. Twenty patients (13 male, median age 27.6 ± 6.8 years) with abnormal sleep history and 10 skeletal neutral configured controls (6 male, median age 29.5 ± 4.2 years) with normal sleep history were examined. Patients and controls were evaluated for apnoea-hypopnoea index (AHI), respiratory disturbance index (RDI), oxygen desaturation index (ODI), snoring volume (dB), total sleep time (TST) and REM-percentage (REM). Airway volumetry was measured via CBCT. Individual user experience for PAT was assessed using the User Experience Questionnaire (UEQ). Patients had significantly higher respiratory scores than controls. AHI increased 4.6-fold (p = .006), RDI 2.5-fold (p = .008) and ODI 6.4-fold (p < .001). Oropharyngeal volumes showed a 30% decrease (p = .003). dB, TST and REM showed no significant differences. AHI (r = -.51; p = .005), ODI (r = -.60; p < .001) and RDI (r = -.45; p = .016) correlated negatively with pharyngeal volume. Wits appraisal correlated negatively with oropharyngeal volume (r = -.47; p = .010) and positively with AHI (r = .41; p = .03) and ODI (r = .49; p = .007). dB and TST (r = -.49; p = .008) and REM and RDI (r = -.43; p = .02) correlated negatively. UEQ-KPI (2.17 ± 0.24) confirmed excellent usability of PAT. Patients with mandibular retrognathia and abnormal sleep history showed significantly higher respiratory indices and smaller oropharyngeal volumes than neutrally configured controls. The dygnathia severity directly influenced the risk of obstructive sleep apnoea.

Managing Vernal Keratoconjunctivitis in Children with Precision Medication: Case Report and Literature Review

ABSTRACT Vernal Keratoconjunctivitis is a chronic inflammatory condition that primarily affects the conjunctiva of both eyes. It is characterized by recurrent episodes of inflammation, often following a seasonal pattern, and is the result of a Type I hypersensitivity reaction. This condition is associated with specific clinical features, including the hypertrophy of papillae in the tarsal conjunctiva and limbus. There are two distinct forms of vernal conjunctivitis, the palpebral and limbal types, each presenting with its own set of clinical features and management considerations. In the case at hand, a 6-year-old male patient presented with active vernal conjunctivitis that had persisted continuously for the past four months. Despite receiving treatment with topical anti-inflammatory eye drops aimed at stabilizing the inflammatory response, the patient's condition did not show significant improvement. The diagnosis of vernal conjunctivitis was established through a thorough patient history evaluation. Additionally, an ophthalmological examination revealed clinical signs, such as ciliary injection (+), hyperemia (+), and pseudogerontoxon (+) in both eyes, further confirming the diagnosis. The management for patient during the acute phase of the disease included the administration of mast cell stabilizers. Topical corticosteroids were also considered to address the inflammation and alleviate the patient's symptoms. The combined therapy approach involving topical mast cell stabilizers and topical corticosteroids ultimately led to a noticeable improvement in the patient's clinical condition and relief from the troublesome symptoms of vernal conjunctivitis. This multidisciplinary management approach highlights the importance of tailoring treatment to the individual patient's needs, considering both the acute and long-term aspects of this chronic ocular condition. Keywords: Vernal Keratoconjunctivitis, Mast Cell Stabilizers, Topical Corticosteroids, Chronic Ocular Disorder.

The Potential of Dendritic Cell Subsets in the Development of Personalized Immunotherapy for Cancer Treatment.

Since the discovery of dendritic cells (DCs) in 1973 by Ralph Steinman, a tremendous amount of knowledge regarding these innate immunity cells has been accumulating. Their role in regulating both innate and adaptive immune processes is gradually being uncovered. DCs are proficient antigen-presenting cells capable of activating naive T-lymphocytes to initiate and generate effective anti-tumor responses. Although DC-based immunotherapy has not yielded significant results, the substantial number of ongoing clinical trials underscores the relevance of DC vaccines, particularly as adjunctive therapy or in combination with other treatment options. This review presents an overview of current knowledge regarding human DCs, their classification, and the functions of distinct DC populations. The stepwise process of developing therapeutic DC vaccines to treat oncological diseases is discussed, along with speculation on the potential of combined therapy approaches and the role of DC vaccines in modern immunotherapy.

A fractional-order mathematical model for lung cancer incorporating integrated therapeutic approaches

This paper addresses the dynamics of lung cancer by employing a fractional-order mathematical model that investigates the combined therapy of surgery and immunotherapy. The significance of this study lies in its exploration of the effects of surgery and immunotherapy on tumor growth rate and the immune response to cancer cells. To optimize the treatment dosage based on tumor response, a feedback control system is designed using control theory, and Pontryagin’s Maximum Principle is utilized to derive the necessary conditions for optimality. The results reveal that the reproduction number (R_0) is 2.6, indicating that a lung cancer cell would generate 2.6 new cancer cells during its lifetime. The reproduction coefficient (R_c) is 0.22, signifying that cancer cells divide at a rate that is 0.22 times that of normal cells. The simulations demonstrate that the combined therapy approach yields significantly improved patient outcomes compared to either treatment alone. Furthermore, the analysis highlights the sensitivity of the steady-state solution to variations in k_5 (the rate of division of cancer stem cells) and k_{13} (the rate of differentiation of cancer stem cells into progenitor cells). This research offers clinicians a valuable tool for developing personalized treatment plans for lung cancer patients, incorporating individual patient factors and tumor characteristics. The novelty of this work lies in its integration of surgery, immunotherapy, and control theory, extending beyond previous efforts in the literature.

ROLE OF CHECKPOINT INHIBITION IN GERMANY

Immune checkpoint inhibition (ICI) has demonstrated an overall excellent benefit-to-risk profile in the treatment of classical Hodgkin lymphoma (cHL); however, cure remains an exception to the rule. The German Hodgkin Study Group (GHSG) has identified several areas of unmet need for ICI development in cHL. First, we aim to better understand the role of immune checkpoints in the interplay between Hodgkin/Reed-Sternberg malignant cells and the abundant microenvironment. Second, we aim to improve efficacy of ICI in multiple relapsed/refractory (r/r) cHL patients, as complete response rates are infrequent and median PFS is still quite limited. Therefore, combination therapies with alternative ICIs targeting TIGIT, LAG3, or TIM3, or combinations with conventional cytotoxic drugs need to be investigated. The GHSG has focused on evaluating the abscopal effects of radiotherapy to improve ICI in multiple r/r cHL. Third, the GHSG strongly believes that ICI should be able to improve first-line therapy of cHL. The GHSG is currently conducting clinical trials to de-escalate the chemotherapy intensity. In early favourable stage cHL patients, we hypothesize that ICI can replace chemotherapy in the combined modality therapy approach. In early unfavourable stage cHL, we use our PET-adapted design to select well-responding patients and remove chemotherapy and/or radiotherapy from the treatment strategy. In advanced stage cHL, we aim to reduce cumulative exposure to conventional chemotherapy. We hypothesize that the combination of anti-PD-1 antibody therapy with our intensive chemotherapy should act synergistically and more patients should achieve an early metabolic complete response. These patients could then be treated with only 4 cycles of combined PD1 chemotherapy. Overall, this new treatment principle should serve to overcome chemotherapy resistance and improve the efficacy of established therapeutic regimens, while reducing the treatment burden for our cHL patients. Keywords: Hodgkin lymphoma, immunotherapy No conflicts of interests pertinent to the abstract.

Objective assessment of mobility among adults with diabetes and end-stage renal disease using walking aid: A cross-sectional cohort study

BackgroundThis cross-sectional study aimed to compare physical activity levels, plantar sensation, and fear of falling between individuals with diabetes undergoing hemodialysis, with or without walking aids. MethodsSixty-four participants were recruited, with 37 not using walking aids (age = 65.8 ± 0.7 years, 46% female) and 27 using walking aids (age = 69.2 ± 1.2 years, 63% female). Physical activity was measured using validated pendant sensors over two consecutive days. Concern for falling and plantar numbness were assessed using the Falls Efficacy Scale-International and vibration perception threshold test, respectively. FindingsParticipants using walking aids exhibited a greater fear of falling (84% vs. 38%, p < 0.01) and fewer walking bouts (p < 0.01, d = 0.67) and stand-to-walk transitions (p < 0.01, d = 0.72) compared to those not using walking aids. The number of walking bouts was negatively correlated with concern for falling scores (ρ = −0.35, p = 0.034) and vibration perception threshold (R = −0.411, p = 0.012) among individuals not using walking aids. However, these correlations were not significant among those using the walking aid. There was no significant group difference in active behavior (walking + standing %) and sedentary behavior (sitting + lying %). InterpretationThose undergoing hemodialysis often lead sedentary lives, with mobility affected by fear of falling and plantar numbness. Using walking aids can help, but it doesn't guarantee more walking. A combined psychosocial and physical therapy approach is key for managing fall concerns and improving mobility.

Combined Transplantation of Human MSCs and ECFCs Improves Cardiac Function and Decrease Cardiomyocyte Apoptosis After Acute Myocardial Infarction.

Ischemic heart disease, often caused by an acute myocardial infarction (AMI) is one of the leading causes of morbidity and mortality worldwide. Despite significant advances in medical and procedural therapies, millions of AMI patients progress to develop heart failure every year. Here, we examine the combination therapy of human mesenchymal stromal cells (MSCs) and endothelial colony-forming cells (ECFCs) to reduce the early ischemic damage (MSCs) and enhance angiogenesis (ECFCs) in a pre-clinical model of acute myocardial infarction. NOD/SCID mice were subjected to AMI followed by transplantation of MSCs and ECFCs either alone or in combination. Cardiomyocyte apoptosis and cardiac functional recovery were assessed in short- and long-term follow-up studies. At 1day after AMI, MSC- and ECFC-treated animals demonstrated significantly lower cardiomyocyte apoptosis compared to vehicle-treated animals. This phenomenon was associated with a significant reduction in infarct size, cardiac fibrosis, and improvement in functional cardiac recovery 4weeks after AMI. The use of ECFCs, MSCs, and the combination of both cell types reduce cardiomyocyte apoptosis, scar size, and adverse cardiac remodeling, compared to vehicle, in a pre-clinical model of AMI. These results support the use of this combined cell therapy approach in future human studies during the acute phase of ischemic cardiac injury.

Panning for gold: Purifying mesencephalic dopaminergic progenitors differentiated from human pluripotent stem cells.

In a recently published study, Xu et al. used two surface markers, CLSTN2 and PTPRO, to generate highly purified donor dopaminergic neurons and achieved stable and predictable therapeutic outcomes by transplantation into the brain of PD animal models (Xu et al., 2022).

Combining Dance/MovementTherapy with CognitiveBehavioralTherapy in Treatment of Children with Anxiety Disorders: Factors Explaining Therapists' Attitudes.

Anxiety disorders (ADs) are among the most common psychiatric disorders and they may appear as early on as in childhood. The current study addressed the combination of two treatments approaches for ADs: Dance/movement therapy (DMT) and cognitive behavioral therapy (CBT), focusing on factors that explain the therapists' attitudes towards actually combining the two therapies. The study utilized a quantitative design, with a perceptions survey administered via an online questionnaire. Ninety-nine therapists participated in the study (DMT-only n = 35, CBT-only n = 42, and DMT + CBT, n = 22). Following preliminary analysis (comparison between the groups, correlations and factor analysis), the structural equation model (SEM, confirmatory factor analysis) revealed a good fit between the theoretical model and the empirical data. First, it was found that the reported actual use of the combined approaches (DMT + CBT) in treatment of children with ADs, was significantly explained by therapists who had experience practicing DMT but not CBT perceiving this combination as efficient. Second, the therapists' use of the combined therapy (DMT + CBT) approaches was not related to their sense of efficacy as therapists of children with ADs. The model represents concordance between the components of the therapists' attitudes: Affective—belief that it is efficient, cognitive—perception of it as effective, and behavioral—their actual use.