A Multi-Faceted Digital Health Solution for Monitoring and Managing Diabetic Foot Ulcer Risk: A Case Series.

INTRODUCTION: Diabetic foot ulcers (DFU) are a devastating complication of diabetes. There are numerous challenges with preventing diabetic foot complications and barriers to achieving the care processes suggested in established foot care guidelines. Multi-faceted digital health solutions, which combine multimodal sensing, patient-facing biofeedback, and remote patient monitoring (RPM), show promise in improving our ability to understand, prevent, and manage DFUs. METHODS: Patients with a history of diabetic plantar foot ulcers were enrolled in a prospective cohort study and equipped with custom sensory insoles to track plantar pressure, plantar temperature, step count, and adherence data. Sensory insole data enabled patient-facing biofeedback to cue active plantar offloading in response to sustained high plantar pressures, and RPM assessments in response to data trends of concern in plantar pressure, plantar temperature, or sensory insole adherence. Three non-consecutive case participants that ultimately presented with pre-ulcerative lesions (a callus and/or erythematous area on the plantar surface of the foot) during the study were selected for this case series. RESULTS: Across three illustrative patients, continuous plantar pressure monitoring demonstrated promise for empowering both the patient and provider with information for data-driven management of pressure offloading treatments. CONCLUSION: Multi-faceted digital health solutions can naturally enable and reinforce the integrative foot care guidelines. Multi-modal sensing across multiple physiologic domains supports the monitoring of foot health at various stages along the DFU pathogenesis pathway. Furthermore, digital health solutions equipped with remote patient monitoring unlock new opportunities for personalizing treatments, providing periodic self-care reinforcement, and encouraging patient engagement-key tools for improving patient adherence to their diabetic foot care plan.

Modulatory Effects of Hydatid Cyst Fluid on a Mouse Model of Experimental Autoimmune Encephalomyelitis.

The reduced burden of helminth parasites in industrialized countries is probably one of the reasons for the increased prevalence of autoimmune disorders such as multiple sclerosis (MS). The current study aimed to evaluate the potential preventive effects of hydatid cyst fluid (HCF) on the disease severity in an EAE mouse model of MS. EAE-induced mice were treated with HCF before and after EAE induction. An RT-PCR-based evaluation of IFN-γ, IL-1ß, TNF, T-bet, IL-4, GATA3, IL-17, RoRγ, TGF-ß, and FOXP3 expression levels in splenocytes and an ELISA-based analysis of IFN-γ and IL-4 levels in cell culture supernatant of splenocytes were performed. Histopathological examinations of mice during the study were also conducted. The expression levels of T-bet, IL-4, GATA3, TGF-ß, and FOXP3 in EAE + HCF mice were significantly higher compared to EAE + PBS mice. In the EAE + HCF group, the expression levels of IFN-γ, IL-1ß, and TNF were significantly lower than in the EAE + PBS group. The histopathological results showed significantly reduced inflammation and demyelination in EAE + HCF mice compared to EAE + PBS mice. Our study provides proof-of-concept in the EAE mouse model of MS that helminth-derived products such as HCF have a potential prophylactic effect on MS development and present a novel potential therapeutic strategy.

Potential roles of lncRNA MALAT1-miRNA interactions in ocular diseases.

Long non-coding RNAs (lncRNAs) are non-protein coding transcripts that are longer than 200 nucleotides in length. LncRNAs are implicated in gene expression at the transcriptional, translational, and epigenetic levels, and thereby impact different cellular processes including cell proliferation, migration, apoptosis, angiogenesis, and immune response. In recent years, numerous studies have demonstrated the significant contribution of lncRNAs to the pathogenesis and progression of various diseases, such as stroke, heart disease, and cancer. Further investigations have shown that lncRNAs have altered expression patterns in ocular tissues and cell lines during pathological conditions. The pathogenesis of various ocular diseases, including glaucoma, cataract, corneal diseases, proliferative vitreoretinopathy, diabetic retinopathy, and retinoblastoma, is influenced by the involvement of specific lncRNAs which play a critical role in the development and progression of these diseases. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a well-researched lncRNA in the context of ocular diseases, which has been shown to exert its biological effects through several signaling pathways and downstream targets. The present review provides a comprehensive summary of the molecular mechanisms underlying the biological functions and roles of MALAT1 in ocular diseases.

Preventative Sensor-Based Remote Monitoring of the Diabetic Foot in Clinical Practice.

Diabetes and its complications, particularly diabetic foot ulcers (DFUs), pose significant challenges to healthcare systems worldwide. DFUs result in severe consequences such as amputation, increased mortality rates, reduced mobility, and substantial healthcare costs. The majority of DFUs are preventable and treatable through early detection. Sensor-based remote patient monitoring (RPM) has been proposed as a possible solution to overcome limitations, and enhance the effectiveness, of existing foot care best practices. However, there are limited frameworks available on how to approach and act on data collected through sensor-based RPM in DFU prevention. This perspective article offers insights from deploying sensor-based RPM through digital DFU prevention regimens. We summarize the data domains and technical architecture that characterize existing commercially available solutions. We then highlight key elements for effective RPM integration based on these new data domains, including appropriate patient selection and the need for detailed clinical assessments to contextualize sensor data. Guidance on establishing escalation pathways for remotely monitored at-risk patients and the importance of predictive system management is provided. DFU prevention RPM should be integrated into a comprehensive disease management strategy to mitigate foot health concerns, reduce activity-associated risks, and thereby seek to be synergistic with other components of diabetes disease management. This integrated approach has the potential to enhance disease management in diabetes, positively impacting foot health and the healthspan of patients living with diabetes.

Microscopic and Molecular Identification of Cyclospora cayetanensis and Cystoisospora belli in HIV-Infected People in Tabriz, Northwest of Iran.

Opportunistic pathogens such as Cryptosporidium, Cystoisospora belli, and Cyclospora cayetanensis cause various gastrointestinal and non-digestive disorders in people with HIV/AIDS. These symptoms are especially severe in HIV-infected people who have a CD4+ count of less than 200 cells/mL. This study aimed to determine the prevalence of C. belli and C. cayetanensis infections among people living with HIV in Tabriz, northwest of Iran. This descriptive study was performed on 137 people with HIV who had been referred to behavioral disease counseling centers in Tabriz. Then, after receiving written consent, fecal samples were collected and evaluated for the detection of parasitic infections using direct methods and modified acid fast staining, as well as polymerase chain reaction (PCR).From the 137 fecal samples collected (98 males and 39 females, between 20 and 40 years old), 1.5% were positive for C. cayetanensis and 2.9% were positive for C. belli. Due to the prevalence of C. cayetanensis and C. belli in people with HIV in Tabriz, essential measures, including personal hygiene training for infection control and prevention, seem necessary.

Predicting vertical and shear ground reaction forces during walking and jogging using wearable plantar pressure insoles.

BACKGROUND: The development of plantar pressure insoles has made them a potential replacement for force plates. These wearable devices can measure multiple steps and might be used outside of the lab environment for rehabilitation and evaluation of sport performance. However, they can only measure the vertical force which does not completely represent the vertical ground reaction force. In addition, they are not able to measure shear forces which play an import role in the dynamic performance of individuals. Indirect approaches might be implemented to improve the accuracy of the force estimated by plantar pressure systems. RESEARCH QUESTION: The aim of this study was to predict the vertical and shear components of ground reaction force from plantar pressure data using recurrent neural networks. METHODS: Ground reaction force and plantar pressure data were collected from 16 healthy individuals during 10 trials of walking and five trials of jogging using Bertec force plates at 1000 Hz and FScan plantar pressure insoles at 100 Hz. A long short-term memory neural network was built to consider the time dependency of pressure and force data in predictions. The data were split into three subsets of train, to train the model, evaluate, to optimize the model hyperparameters, and test sets, to assess the accuracy of the model predictions. RESULTS: The results of this study showed that our long short-term memory model could accurately predict the shear and vertical force components during walking and jogging. The predictions were more accurate during walking compared to jogging. In addition, the predictions of mediolateral force had higher error and lower correlation compared to vertical and anteroposterior components. SIGNIFICANCE: The long short-term memory model developed in this study may be an acceptable option for accurate estimation of ground reaction force during outdoor activities which can have significant impacts in rehabilitation, sport performance, and gaming.

The Therapeutic Effects of Curcumin-coated Gold Nanoparticle Against Leishmania Major Causative Agent of Zoonotic Cutaneous Leishmaniasis (ZCL): An In Vitro and In Vivo Study.

We synthesized and characterized curcumin-coated gold nanoparticles (Cur@AuNPs) and investigated their stability, cytotoxicity, leishmanicidal activity in in vitro and in in vivo experiments. Cur@AuNPs synthesized through a simple one-pot green chemistry technique. The in vitro leishmanicidal activity of curcumin-coated gold nanoparticles against extracellular promastigotes and intracellular amastigotes of protozoan parasite Leishmania major (L. major) was determined by applying the tetrazolium reduction colorimetric quantitative MTT technique. For in vivo assessment, the footpad lesion size and parasite burden in two infection site organs including lymph nodes and footpads of susceptible BALB/c mice infected with L. major were measured. Mice immune responses in all study groups were quantified by measuring the levels of gamma interferon (IFN-γ) and interleukin-4 (IL-4). Viability of Leishmania promastigotes significantly diminished with the inhibition in promastigotes growth (IC50) of 64.79 µg/mL and 29.89 µg/mL for 24 h and 48 h, respectively. In vitro nanoparticles treatment efficiently cleared the L. major amastigotes explanted in macrophages but had no harmful toxicity on the mice cells. In the in vivo condition, in the treated infected BALB/c mice the CL lesion size, Leishmania parasite burden, and IL-4 were decreased, while IFN-γ was significantly increased. The results suggest that Cur@AuNP was an effective compound against Leishmania parasite in vitro and in vivo, efficiently induced T-helper 1 (Th1) responses and augmented host cellular immune responses, and ending in a reduced Leishmania parasite burden. Therefore, it may be identified as a novel potential therapeutic approach for the local therapy of zoonotic CL treatment with high cure rates.

Long non-coding RNAs involved in retinoblastoma.

INTRODUCTION: Retinoblastoma (RB) is the most common childhood tumor that can occur in the retina and develop in a sporadic or heritable form. Although various traditional treatment options have been used for patients with RB, identifying novel strategies for childhood cancers is necessary. MATERIAL AND METHODS: Recently, molecular-based targeted therapies have opened a greater therapeutic window for RB. Long non-coding RNAs (lncRNAs) presented a potential role as a biomarker for the detection of RB in various stages. CONCLUSION: LncRNAs by targeting several miRNA/transcription factors play critical roles in the stimulation or suppression of RB. In this review, we summarized recent progress on the functions of tumor suppressors or oncogenes lncRNAs in RB.

Capsulectomy Shunt Revision versus Repeat Shunt Implantation Following Ahmed Glaucoma Valve Failure in Refractory Glaucoma.

PURPOSE: To investigate the efficacy of capsulectomy shunt revision (CSR) compared with the implantation of a second Ahmed glaucoma valve (re-AGV) in glaucoma patients with failed shunts. DESIGN: Quasi-experimental study. SUBJECTS: Forty-six eyes with failed Ahmed glaucoma valves (AGVs) were included in the study; 25 underwent CSR, whereas 21 underwent re-AGV. METHODS: Patients were scheduled for CSR or re-AGV based on the appearance and accessibility of the existing AGV versus the feasibility for re-AGV in other quadrants. The CSR involved incision and dissection down to the thick fibrous capsule around the AGV plate, which was excised extensively. For re-AGV, the second shunt was implanted in the supranasal or infranasal quadrants. MAIN OUTCOME MEASURES: Surgical success, defined as intraocular pressure (IOP) > 5 mmHg, ≤ 21 mmHg, IOP reduction ≥ 20% from baseline, and no reoperation for glaucoma. Secondary outcome measures were IOP, number of glaucoma medications, and complications during a 12-month follow-up period. RESULTS: Mean IOP was significantly lower than preoperative values at all time points in both study groups (P < 0.001). Intraocular pressure decreased significantly from 28.3 ± 5.04 mmHg at baseline to 16.4 ± 2.4 mmHg at final follow-up in the capsulectomy group (P = 0.002). Corresponding IOP values for re-AGV were 30.99 ± 6.2 and 13.6 ± 3.8 mmHg, respectively (P = 0.001). Intraocular pressure in the CSR group was higher than re-AGV during the study (P = 0.003). The cumulative probability of success at 12 months was significantly higher in the re-AGV group (87.5% vs 53.3%, P = 0.002). There was no significant difference in the number of glaucoma medications and overall complications rate between the study groups. Wound leakage was the only complication more common in the CSR group (P = 0.012). CONCLUSION: In the eyes with a failed AGV, re-AGV and CSR are both effective. Implantation of a second shunt seems more effective than the surgical revision of an existing device; however, the latter procedure may be a viable option in selected cases. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Computationally efficient model to predict the deformations of a cellular foot orthotic.

BACKGROUND: Foot orthotics (FOs) are frequently prescribed to provide comfortable walking for patients. Finite element (FE) simulation and 3D printing pave the way to analyse, optimize and fabricate functionally graded lattice FOs where the local stiffness can vary to meet the therapeutic needs of each individual patient. Explicit FE modelling of lattice FOs with converged 3D solid elements is computationally prohibitive. This paper presents a more computationally efficient FE model of cellular FOs. METHOD: The presented FE model features shell elements whose mechanical properties were computed from the numerical homogenization technique. To verify the results, the predictions of the homogenized models were compared to the explicit model's predictions when the FO was under a static pressure distribution of a foot. To validate the results, the predictions were also compared with experimental measurements when the FO was under a vertical displacement at the medial longitudinal arch. RESULTS: The verification procedure showed that the homogenized model was 46 times faster than the explicit model, while their relative difference was less than 8% to predict the local minimum of out-of-plane displacement. The validation procedure showed that both models predicted the same contact force with a relative difference of less than 1%. The predicted force-displacement curves were also within a 90% confidence interval of the experimental measurements having a relative difference smaller than 10%. In this case, using the homogenized model reduced the computational time from 22 h to 22 min. CONCLUSION: The presented homogenized model can be therefore employed to speed up the FE simulation to predict the deformations of the cellular FOs.

Corneal biomechanical changes after Descemet stripping automated endothelial keratoplasty, penetrating keratoplasty, and phacoemulsification.

PURPOSE: To evaluate corneal biomechanical changes after Descemet stripping automated endothelial keratoplasty (DSAEK), penetrating keratoplasty (PK), and phacoemulsification (PE). METHODS: This prospective study included 138 eyes which underwent PK (26 eyes), DSAEK (26 eyes), PE (57 eyes), and 29 normal eyes. Intraocular pressure (IOP) was measured by Goldmann applanation tonometer (GAT), and central corneal thickness (CCT) and axial length by ultrasound. The ocular response analyzer was used to measure corneal hysteresis (CH), corneal resistance factor (CRF), Goldmann-related IOP (IOPg), and cornea-compensated IOP (IOPcc) preoperatively and 1, 3, and 6 months postoperatively. RESULTS: At baseline, PK group had the lowest CH and CRF. There was a significant increase in CH and CRF to normal values in PK (P = 0.015 and 0.006) and PE (P = 0.005 and 0.0001) groups over the study period. At 6 months, CH and CRF increased and reached normal values in the PK group; increased to a lower level than normal in the DSAEK group; and, after an initial reduction, increased to normal values in the PE group. At 6 months, DSAEK group had the lowest CH and CRF. There was a significant positive correlation between CRF and GAT (r = 0.281, P = 0.009), IOPg and GAT (r = 0.335, P = 0.001), and IOPcc and GAT (r = 0.282, P = 0.001). CH was negatively correlated with age (r = - 0.189, P = 0.04). CONCLUSION: Corneal biomechanical factors increase after DSAEK and PK. At post-operative month six, they reach normal values in PK group, but are lower than normal in DSAEK group.

Effect of 3D printed foot orthoses stiffness on muscle activity and plantar pressures in individuals with flexible flatfeet: A statistical non-parametric mapping study.

BACKGROUND: The 3D printing technology allows to produce custom shapes and add functionalities to foot orthoses which offers better options for the treatment of flatfeet. This study aimed to assess the effect of 3D printed foot orthoses stiffness and/or a newly design posting on muscle activity, plantar pressures, and center of pressure displacement in individuals with flatfeet. METHODS: Nineteen individuals with flatfeet took part in this study. Two pairs of foot orthoses with different stiffness were designed for each participant and 3D printed. In addition, the flexible foot orthoses could feature an innovative rearfoot posting. Muscle activity, plantar pressures, and center of pressure displacement were recorded during walking. FINDINGS: Walking with foot orthoses did not alter muscle activity time histories. Regarding plantar pressures, the most notable changes were observed in the midfoot area, where peak pressures, mean pressures and contact area increased significantly during walking with foot orthoses. The latter was reinforced by increasing the stiffness. Concerning the center of pressure displacement, foot orthoses shifted the center of pressure forward and medially at early stance. At the end of the stance phase, a transition of the center of pressure in posterior direction was observed during the posting condition. No effect of stiffness was observed on center of pressure displacement. INTERPRETATION: The foot orthoses stiffness and the addition of posting influenced plantar pressures during walking. The foot orthoses stiffness mainly altered the plantar pressures under the midfoot area. However, posting mainly acted on peak and mean pressures under the rearfoot area.

Understanding the role of foot biomechanics on regional foot orthosis deformation in flatfoot individuals during walking.

BACKGROUND: Foot orthoses (FOs) are one of the most common interventions to restore normal foot mechanics in flatfoot individuals. New technologies have made it possible to deliver customized FOs with complex designs for potentially better functionalities. However, translating the individuals' biomechanical needs into the design of customized FOs is not yet fully understood. RESEARCH QUESTION: Our objective was to identify whether the deformation of customized FOs is related to foot kinematics and plantar pressure during walking. METHODS: The kinematics of multi-segment foot and FOs contour were recorded together with plantar pressure in 17 flatfoot individuals while walking with customized FOs. The deformation of FOs surface was predicted from its contour kinematics using an artificial neural network. Plantar pressure map and deformation were divided into five anatomically based regions defined by the corresponding foot segments. Forward stepwise linear mixed models were built for each of the four gait phases to determine the feet-FOs interaction. RESULTS: It was observed that some associations existed between foot kinematics and pressure with regional FOs deformation. From heel-strike to foot-flat, longitudinal arch angle was associated with FOs deformation in forefoot. From foot-flat to midstance, rearfoot eversion accounted for variation in the deformation of medial FOs regions, and forefoot abduction for the lateral regions. From midstance to heel-off, rearfoot eversion, longitudinal arch angle, and plantar pressure played significant role in deformation. Finally, from heel-off to toe-off, forefoot adduction affected the deformation of forefoot and midfoot. SIGNIFICANCE: This study provides guidelines for designing customized FOs. Flatfoot individuals with excessive rearfoot eversion or very flexible medial arches require more support on medial FOs regions, while the ones with excessive forefoot abduction need the support on lateral regions. However, a compromise should be made between the level of support and the level of increase in plantar pressure to avoid stress on foot structures.

Prenatal diagnosis of primary congenital glaucoma and histopathological features in a fetal globe with cytochrome p4501B1 mutations.

BACKGROUND/OBJECTIVES: This study aims to report the developmental and histopathological features of ocular tissues from an electively aborted human fetus with mutations in cytochrome p4501B1, and thus predisposed to primary congenital glaucoma in comparison to an age-matched healthy fetal globe. SUBJECTS/METHODS: Both eyes of two 17-week gestational aged fetuses, the first with CYP1B1 mutations and the second as healthy control fetus, were studied. Hematoxylin and eosin, Periodic acid-Schiff, Gomori's trichrome, and Verhoeff-Van Gieson staining protocols in addition to immunohistochemistry staining using anti-cytochrome p4501B1, anti-fibrillin-1, and anti-4-hydroxy-2-nonenal antibodies, as primary antibodies, were performed to assess the effect of the mutations on tissue development, cytochrome p4501B1 protein expression, extracellular matrix structure, and oxidative stress in the developing fetus eye. Quantitative analyses were performed using ImageJ software. Student's t-test was used for statistical analysis and P-values <0.05 were considered as significant. RESULTS: Delayed development in ocular tissues, decreased expression of cytochrome p4501B1 protein, irregular extracellular matrix structure, and increased oxidative stress biomarker were evident in the ocular tissues of the fetus with cytochrome p4501B1 mutations as compared to a normal globe from an age-matched fetus. CONCLUSION: To the best of our knowledge, this is the first report of prenatal diagnosis of primary congenital glaucoma. We also describe histopathological changes in the primary congenital glaucoma-affected globes revealing the effect of cytochrome p4501B1 deficiency on ocular tissues during early fetal development contributing to the glaucoma phenotype.

Intraocular Pressure Changes in the Contralateral Eye After Glaucoma Surgery.

PRCIS: Glaucoma surgery in 1 eye can result in significant intraocular pressure (IOP) elevation in the fellow eye in a significant percentage of subjects. This effect is more pronounced following glaucoma drainage device implantation and in subjects developing postoperative hypotony in the first eye. PURPOSE: The aim was to investigate the course and magnitude of IOP changes in contralateral eyes following glaucoma surgery. PATIENTS AND METHODS: We studied 131 glaucoma patients undergoing surgery. IOP changes in fellow eyes and the number of glaucoma medications were recorded for 6 months. Both normal and glaucomatous fellow eyes were included. Patients on preoperative acetazolamide were analyzed separately. IOP change ≥4 mm Hg or 20% increase from baseline values was considered significant. RESULTS: Baseline IOP in fellow eyes was 13.1±3.3 mm Hg which increased significantly at all-time points with a peak at 1 week (mean increase: 3.1±3.2 mm Hg) gradually decreasing up to 6 months (mean increase 0.9±2.1 mm Hg). The number of fellow eyes with clinically significant IOP elevation at 1 day, 1 week, and 1, 3. and 6 months was 47, 76, 47, 31, and 37 showing mean IOP rise of 4.5±2.3 (38.5%), 5.4±1.8 (48.5%), 4.8±1.6 (44.2%), 3.7±1.3 (36.5%), and 3.2±1.3 (32.6%) mm Hg, respectively. Medications were added to 18 fellow eyes (including 10 initially "normal" eyes) while 7 other fellow eyes required surgery.Significant IOP elevation in fellow eyes was associated with tube shunt surgery (P<0.008 at all-time points), a diagnosis of glaucoma following cataract surgery, IOP ≤5 mm Hg on the first postoperative day (P=0.002) and use of preoperative acetazolamide. CONCLUSION: Glaucoma surgery was associated with IOP elevation in fellow eyes in a significant number of subjects and suggests that IOP in the unoperated eye should also be checked at postoperative visits.

Anti-Leishmanial Activity of Artemisia persica, A. spicigera, and A. fragrance against Leishmania major.

BACKGROUND: Neglected tropical diseases (NTDs) like zoonotic cutaneous leishmaniasis (ZCL), is a widespread infectious disease with high mortality and morbidity. Various medications are used for treating the disease, but several side effects and drug resistance have been reported. Herbal medicines are unlimited sources for discovering new medications to treat infectious diseases. We aimed to determine the leishmanicidal activity of three species of Iranian Artemisia herbal plant extracts in in-vitro. METHODS: In-vitro anti-leishmanial activity of ethanolic extracts on both promastigotes and amastigotes was determined by using MTT method. IC50, CC50, EC50 and SI were calculated. The study was done in 2019-2020 in Iran University of Medical Sciences, Tehran, Iran. RESULTS: All of the three Artemisia species significantly reduced the number of parasite promastigotes. Among them, A. persica had the highest leishmanicidal activity against parasite promastigotes. Cytotoxicity assay elucidated that the Artemisia had no toxicity to the host cells, and killed the L. major amastigotes very efficiently. By increasing the dose of extracts, the parasite number in both phases (promastigotes and amastigotes) was reduced significantly. CONCLUSION: These results indicated satisfactory anti-leishmanial activity of Artemisia extracts against ZCL in-vitro. Accordingly, Artemisia ethanolic extracts might be considered as a strong, effective and safe herbal compound for clearing the L. major with less toxicity to the host macrophages cells. Hence, it may be recognized as an excellent herbal therapy for treating the ZCL.

Effects of body weight support and guidance force settings on muscle synergy during Lokomat walking.

BACKGROUND: The Lokomat is a robotic device that has been suggested to make gait therapy easier, more comfortable, and more efficient. In this study, we asked whether the Lokomat promotes physiological muscle activation patterns, a fundamental question when considering motor learning and adaptation. METHODS: We investigated lower limb muscles coordination in terms of muscle activity level, muscle activity pattern similarity, and muscle synergy in 15 healthy participants walking at 3 km/h on either a treadmill or in a Lokomat at various guidance forces (GF: 30, 50 or 70%) and body weight supports (BWS: 30, 50 or 70% of participant's body weight). RESULTS: Walking in the Lokomat was associated with a greater activation level of the rectus femoris and vastus medialis (×2-3) compared to treadmill walking. The level of activity tended to be diminished in gastrocnemius and semi-tendinosus, which particularly affected the similarity with treadmill walking (normalized scalar product NSP = 0.7-0.8). GF and BWS independently altered the muscle activation pattern in terms of amplitude and shape. Increasing BWS decreased the level of activity in all but one muscle (the soleus). Increasing GF slightly improved the similarity with treadmill walking for the tibialis anterior and vastus medialis muscles. The muscle synergies (N = 4) were similar (NSP = 0.93-0.97), but a cross-validation procedure revealed an alteration by the Lokomat. The activation of these synergies differed (NSP = 0.74-0.82). CONCLUSION: The effects of GF and BWS are modest compared to the effect of the Lokomat itself, suggesting that Lokomat design should be improved to promote more typical muscle activity patterns.

Anti-pronator components are essential to effectively alter lower-limb kinematics and kinetics in individuals with flexible flatfeet.

BACKGROUND: Foot orthoses are commonly used to correct for foot alterations and especially address excessive foot pronation in individuals with flatfeet. In recent years, 3D printing has taken a key place in orthotic manufacturing processes as it offers more options and can be patient specific. Hence, the purpose of this study was to evaluate whether stiffness of 3D printed foot orthoses and a newly designed rearfoot posting have an effect on lower limb kinematics and kinetics in individuals with flatfeet. METHODS: Nineteen patients with flexible flatfeet were provided two pairs of customized 3D printed ¾ length orthotics. Foot orthoses were of different stiffness and could feature a rearfoot posting, consisting of 2-mm carbon fiber plate. Lower limb kinematics and kinetics were computed using a multi-segment foot model. One-way ANOVAs using statistical non-parametric mapping, refined by effect sizes, were performed to determine the magnitude of the effect between conditions. FINDINGS: Foot orthoses stiffness had little effect on midfoot and forefoot biomechanics. Reductions in midfoot eversion and forefoot abduction were observed during short periods of stance with rigid foot orthoses. Adding the posting had notable effects on rearfoot kinematics and on the ankle and knee kinetics in the frontal plane; it significantly reduced the eversion angle and inversion moment at the ankle, and increased the knee abduction moment. INTERPRETATION: Using an anti-pronator component is more effective than increasing foot orthoses stiffness to observe a beneficial impact of foot orthoses on the control of excessive foot pronation in individuals with flatfeet.

The fatty acid-binding protein (FABP) decreases the clinical signs and modulates immune responses in a mouse model of experimental autoimmune encephalomyelitis (EAE).

BACKGROUND: An increasing body of studies has shown that Fasciola hepatica can affect immune responses. This study explored whether the fatty acid-binding protein (FABP) of F. hepatica can modulate the immune system in a mouse model of experimental autoimmune encephalomyelitis (EAE). METHODS: EAE-induced C57BL/6 mice were treated with vehicle, F. hepatica total extract (TE) or FABP. The clinical signs, body weights, and the expression of IFN-γ, T-bet, IL-4, GATA3, IL-17, RORγ, TGF-ß, FOXP3, IL-10, TNF-α genes and proteins were determined in the isolated CD4+ splenocytes. Besides, the percentage of Treg cells and degree of demyelination were evaluated. RESULTS: We found that TE and FABP treatments decreased the clinical scores, lymphocyte infiltration rate, and demyelinated plaques in EAE mice. The expressions of IL-4 and GATA3 were increased, whereas IL-17 and TNF-α were down-regulated. FABP did not affect the expression of IFN-γ, RORγ, IL-10, and TGF-ß genes or proteins but reduced the expression of T-bet. TE administration did not affect the expression of IL-10 and the Tbet genes, and increased the expression levels of IFN-γ and FOXP3 in CD4+ lymphocytes. Both FABP and TE treatment did not affect the Treg cell percentage. CONCLUSION: This study indicates that F. hepatica FABP and TE can suppress the inflammatory responses in EAE-induced mice and shift the immune system toward Th2 responses. However, FABP exerts stronger anti-inflammatory effects and seems to be more effective than TE for EAE treatment.

Different manifestation of Echinococcus granulosus immunogenic antigens in the liver and lungs of intermediate host.

Hydatidosis is one of the most important zoonotic diseases with a worldwide distribution and it seems that the survival of Echinococcus granulosus in nature for many years, is due to having different mechanisms to escape from the host immune systems. One of these efficient mechanisms is the production of various antigens and proteins by the larva of the parasite and the main purpose of this study is evaluation of manifestation of various antigens in different parts of intermediate host. The hepatic and pulmonary hydatid cysts were gathered from sheep and the antigens of different parts of the cysts (laminated layer, protoscolices and cyst fluid) were separated and analyzed by SDS-PAGE and then transferred to nitrocellulose paper and finally, Western blot analysis was evaluated the immunogenicity of proteins. The antigens of laminated layer, protoscolices and hydatid cyst fluid, in different tissues of the liver and lungs, manifest various proteins and also these antigens are immunogenically different. Also, it is found more immunogenic proteins in the laminated layer than the other parts of the cysts. The various proteins are generated by Echinococcus granulosus larva depending on the type of tissues attacked by the parasite. Increasing the chance of survival may be the main cause of manifestation various antigens in different parts of cysts and host tissues. These antigenic variations might have made diagnostic serologic test unreliable.