Recurrent and severe infections occurred in children with Down Syndrome (DS) due to immunological parameter defects have been reported. The aim of the study is to evaluate the importance of using T-cell receptor excision circle (TREC) and kappa-deleting recombination excision circle (KREC) as molecular markers for immunological investigation of children with DS. The study included 40 non-disjunction trisomy 21 confirmed DS children, and 25 healthy controls. Peripheral blood (PB) was analyzed for lymphocyte subpopulations by flow cytometry, serum immunoglobulin levels, and TREC and KREC copy numbers using quantitative real-time PCR. DS patients showed significantly lower absolute counts of PB T lymphocytes, T helper lymphocytes, T cytotoxic lymphocytes, B lymphocytes, and Natural killer cells, and lower serum IgA, IgG, and IgM levels compared to healthy controls. Copy number of TREC and KREC showed no significant differences between DS patients and healthy controls. There is a significant positive correlation between TREC copy number with a percentage and absolute count of helper T lymphocytes in patients. Also, the KREC copy number was significantly negatively correlated with the age of patients. These findings suggest that copy numbers of TREC and KREC could be useful as molecular markers for immunological evaluation of patients with DS. More than 40 features that may be associated with DS as craniofacial abnormalities, hypotonia, heart defects, duodenal atresia, mental retardation, and dermatoglyphics. Nevertheless, not all features are observed in one individual with DS, but variable features occur to some degree in each individual with trisomy 21, the mechanism for phenotypic variability is not understood2. There are various medical features associate with DS children including short stature, mental retardation, umbilical hernia, etc.3.Down syndrome (DS), trisomy 21, is a common cause of mental sub-normality and is the most common chromosomal abnormality. The frequency of DS is approximately 1:770 births, with a little male predominance4. This may be due to overexpression of chromosome 21 encoded gene products which impairs the immune response in people with DS5. Individuals with DS may have an abnormal immune system as well as a defective lymphocyte count. They could exhibit deficient T lymphocyte response and reduction of immunoglobulins6. However, differences in numerous immune response compartments have been reported. Various subsets of lymphocytes have been discovered to be significantly diminished in youth, and elevated with aging. T and B cell subsets showed reduced levels below 10% of normal in nearly 90% of DS children and below 5% in 60% of them. Early T lymphocyte growth in infancy was not normal7.Recurrent and severe infections have been reported in children with DS mostly respiratory infections8.Anatomic evidences show that immunological insufficiency in DS patients is caused mostly by thymus malfunction, which results from lymphocyte depletion, cortical reduction, loss of corticomedullary delimitation, and thymic medulla hypertrophy of Hassall’s corpuscles. As a result, thymic maturation is aberrant, resulting in phenotypic and functional defects in circulating T lymphocytes9. Moreover, there is a low number of circulating B lymphocytes, T lymphocytes and Natural Killer cells in those children12. Also, functions of T and B lymphocytes have been analyzed in DS. In DS, the proliferative response of lymphocytes to phytohemagglutinin was considerably lower. Not all DS patients have disrupted levels of immunoglobulins, only some DS children exhibit lower IgG levels for age15.Serum levels of immunoglobulins may vary according to the age in DS children. It has been found that the absolute number of IgG and IgA antibodies rises in children after the age of six and IgM levels slightly decreases in adolescence19. Similarly, kappa-deleting recombination excision circle (KREC) are produced during B lymphocyte development as circularized DNA fragments excised from B cell immunoglobulin kappa gene19.During normal development and maturation of T lymphocytes in the thymus, recombination of T lymphocyte receptor gene occurs causing its splice and rearrangement. In this process, DNA segments are excised from T cell receptor (TCR) gene and circularized forming T cell receptor excision circle (TREC). Number of TREC produced can reflect the number of naive T lymphocytes passed through the thymic maturation process and thus the activity of thymus22.TREC and KREC have been used to assess the activity of the immune system in newborn screening for severe combined immunodeficiency disorder (SCID). It has been reported that TREC and KREC are T and B cell development indicators, respectively. They are effective tools for assessing T and B cell activity and immunological reconstitutionIn this study, we intended to evaluate the immunological profile of DS patients by elucidating the importance of using TREC and KREC as molecular markers for immunological investigation. We investigated percentages and absolute count of peripheral blood (PB) lymphocyte subsets and serum levels of immunoglobulins. Also, we determined copy numbers of TREC and KREC in PB and evaluated their associations with the immunological parameters and the clinical manifestations of DS patients.The study included 40 DS patients aged 6 months to 7 years old. They were 24 males (60%) and 16 females (40%). The median age (Interquartile range (IQR)) at the time of sampling was 1.8 (2) years. Their chromosomal analysis revealed non-disjunction trisomy 21 in all cases. Associated clinical abnormalities e.g. hypothyroidism, mild congenital cardiac anomalies (PFO or ASD), and umbilical hernia were present in some patients ; while KREC showed a ROC curve with a significant AUC value of 0.768, sensitivity 80% and specificity 70% (P ≤ 0.001)  value of 0.837 with a sensitivity of 93% and specificity of 65% (01) Fig. , Table 27 and Huggard et al.23 have demonstrated that the lower absolute counts of immune cells and immunoglobulin levels observed in individuals with DS may contribute to an increased susceptibility to infections and a reduced ability to mount an effective immune response. Also, Dieudonné et al.24 have reported immune dysfunction in DS patients. Our association analysis showed that the percentage and absolute count of B lymphocytes and percentage of helper T cells have significant negative associations with the age of patients. This is in agreement with a study by Froňková et al.18 who demonstrated a reduction of absolute B and T lymphocyte counts with aging. However, there are no significant associations between the immunological parameters of our DS patients and their associated hypothyroidism, congenital heart anomalies, or umbilical hernia.The results presented in this study provide insights into the immunological profile of DS patients and their potential associations with clinical manifestations. The baseline characteristics of the study participants showed a predominantly male population with a median age of 1.8 years. The cumulative clinical manifestations of patients included thyroid, cardiac, and hernia disorders. The immunological profile analysis have revealed that the percentages of T lymphocytes, T helper lymphocytes, T cytotoxic lymphocytes, B lymphocytes, and natural killer cells in PB of DS patients are comparable to those of healthy controls, while their absolute counts are lower in patients than those of controls. Moreover, DS patients have lower immunoglobulin levels  in serum compared to controls. Our findings are consistent with previous studies on the immune system in individuals with DS. Ram and Chinen27.This study has found that there are no significant differences in TREC and KREC copy numbers between DS patients and healthy controls. Moreover, no associations have been found between TREC and KREC copy numbers and the clinical characteristics of DS patients. In contrast, other studies have found that the copy numbers of TREC and KREC were significantly lower in DS patients compared to healthy controls, suggesting a decrease in the output of newly produced T and B cells in DS patients which may contribute to immune defects and increased susceptibility to infections observed in individuals with DS28 showed a positive association between TREC and the percentage of CD4 and CD8 T lymphocytes, recommending that TREC may be a useful biomarker for monitoring immunological insufficiency in DS patients. Additionally, we observed a significant negative correlation between copy numbers of KREC and age in DS patients, which is consistent with previous studies which reported age-related declines in thymic and bone marrow outputs30, suggesting that KREC could be a helpful biomarker for monitoring age-related immune defects in DS patients.Interestingly, our study has found a significant positive correlation between TREC copy number and the percentage and absolute count of CD4 T lymphocytes in DS patients indicating a relationship between the molecular markers and the respective lymphocyte subsets. Similarly, a study by McCullough et al.31.Furthermore, we have performed ROC curve analysis to assess the diagnostic accuracy of TREC and KREC copy numbers as molecular markers for immune insufficiency in DS patients. Our findings showed good significant AUC values, with TREC having a sensitivity of 93% and specificity of 65%, and KREC having a sensitivity of 80% and specificity of 70%. ROC curve analysis demonstrated that TREC and KREC have high sensitivity and specificity for detecting immune defects in DS patients, indicating that these biomarkers have potential diagnostic value for immune dysregulation in DS. This matched with other studies that found that TREC and KREC had high sensitivity and specificity for detecting immune deficiency, supporting their potential utility as molecular markers for immunological investigations in DS populationThe main limitation of our study included the small sample size, which may limit the detection of significant associations between TREC/KREC and clinical data of DS patients. Therefore, further researches on a large sample size are needed in the future to investigate the clinical associations with TREC/KREC in DS patients.Our study provides evidence of immune defects in DS patients, as well as the potential utility of TREC and KREC as molecular markers for immunological evaluation of those patients. The findings also highlight the importance of considering age-related changes in the immunological profile of those patients when interpreting immunological data. However, there is a need for large-scale studies to confirm these findings.This study was approved by the ethics committee of the National Research Centre, Egypt with an approval number 19267 and has therefore been performed under the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All samples were obtained with the written informed consent of the parent/guardian of all children involved in this study before their enrollment.This study included 40 DS patients and 25 healthy subjects matched for age and sex (age range: 6 months to 7 years). They were recruited from the Developmental Assessment and Genetic Disorders Clinic, National Research Centre, Egypt. Enrolled children were subjected to history taking, pedigree analysis, and meticulous clinical examinations. G-banding chromosomal analysis was performed on all patients to confirm the diagnosis of trisomy 21. A thyroid profile, electrocardiogram (ECG), and abdominal sonar were done for all DS patients to exclude or confirm any associated anomalies. Demographic and cumulative clinical manifestations were recorded. Subjects with missing values were excluded during collecting data before beginning of the study. Follow-up observation time was one year.32.PB samples were collected from patients and healthy controls in tubes containing EDTA.50 μL of EDTA-treated PB were incubated for 30 min at 4 °C in the dark with fluorochrome-labeled monoclonal antibodies (mAbs): Fluorescein Isothiocyanate (FITC)-conjugated CD3, Allophycocyanin (APC)-conjugated CD19, Phycoerythrin (PE)-conjugated CD4, FITC-conjugated CD8, and PE-conjugated CD16 . Red blood cells were lysed using BD FACS Lysing Solution . The stained cells were then washed and resuspended in phosphate-buffered saline. Approximately 30,000 stained cells in each sample were analyzed with a BD Accuri™ C6 Flow Cytometer (BD Biosciences). The lymphocytes were gated by setting the appropriate forward scatter/side scatter axes. Data were acquired and data analysis was performed by the BD Accuri™ C6 software programSerum immunoglobulin levels  were determined in patients and healthy controls using Human ELISA kits  according to the manufacturer’s instructions.DNA was isolated from 200 µl of PB using QIAamp DNA Blood Mini Kit  by following the manufacturer’s instructions.6, 105, 104, 103, 102, and 10) of the linearized triple-insert plasmid DNA  that amplified in each PCR plate33.Copy numbers of TREC and KREC were determined using Quantitative Real-Time PCR assay performed on the 7500 Fast Real-Time PCR (Applied Biosystems). Primers and probes of TREC, KREC, and the reference gene TRAC were designed according to Sottini et al. (2010). TaqMan Universal master mix (Applied Biosystems) was used in the reaction. The protocol of reaction was as follows: 50 °C for 2 min, 95 °C for 10 min, followed by 45 cycles at 95 °C for 15 s and 60 °C for 1 min. TREC, KREC, and TRAC copy numbers were obtained by deducing the respective sample quantities from the standard curve obtained by serial dilutions . The Non-parametric Mann–Whitney U test was used for comparing the immunological parameters and immunoglobulin levels between groups of the study. Associations among the immunological parameters, immunoglobulin levels, TRECs and KRECs, age, and the clinical manifestations of patients were analyzed using Spearman’s rank correlation. Data were presented as mean ± SD or median (IQR). A


Macular telangiectasia (MacTel) type 2 is observed in patients in their 5th–8th decades of life. The clinical and imaging findings in younger patients is unknown in larger cohorts. The study purpose is to report prevalence, baseline clinical and spectral domain optical coherence tomography (SDOCT) findings in young MacTel patients below 40 years.This hospital-based, multicentre, retrospective, cross-sectional study included patients between 2011 and 2023. Retinal photographs from multiple imaging techniques were evaluated to diagnose and stage type 2 MacTel and describe their SDOCT findings. Imaging characteristics were correlated with clinical stages and visual acuity.Among all MacTel patients seen in hospital, prevalence of young MacTel cases less than age 40 was 1.77% . Youngest participant was 34 years, while mean age was 38.44 ± 1.795 years. Sixteen patients (50%) were diabetics. Perifoveal greying  and perifoveal hyperreflective middle retinal layers  were the most prevalent clinical and SDOCT imaging finding respectively. Less than 10% (n = 6) eyes had proliferative disease. Presence of retinal pigment clumps (RPC)  coincided with proliferative MacTel. Poor vision was associated with presence of outer retinal layer SDOCT findings like outward bending of inner retinal layers (p = 0.047), RPC (p = 0.007), subfoveal neurosensory detachment (p = 0.048) and subretinal neovascular membrane (p = 0.001).Type 2 MacTel before age 40 is rare, common in women and diabetics, and affects vision in advanced stage. Disease symmetry, comparison with older cases, and longitudinal SDOCT changes in such patients require further study. Type 2 macular telangiectasia (MacTel) is commonly observed in the older population, primarily impacting individuals between the ages of 40 and 80 years . AccordiTo address this research question, a study was conducted with the aim of describing the prevalence, baseline clinical, and imaging characteristics of a cohort of hospital-based patients with type 2 MacTel who were diagnosed before the age of forty years. The findings of this study have the potential to be a valuable asset for enhancing comprehension of disease pathogenesis, pinpointing the modifiable risk factors accountable for disease onset and prevention, and formulating treatment strategies that could delay the progression to an advanced disease stage, thereby mitigating the risk of vision impairment.In this multicentre, retrospective observational hospital-based study, we identified and reviewed the electronic medical records [eye SMART EMR  and NETRAM Ophthalmology EMR ] and spectral domain optical coherence tomography (SDOCT) images of patients ≤ 40 years of age who were initially diagnosed with type 2 MacTel between January 2011 to April 2023. The data was collected and compiled from two tertiary eye care institutes in South India. The study adhered with the tenets of the Declaration of Helsinki and was approved by the local Institutional Review Board/Ethics Committee.The diagnosis of type 2 MacTel was made based on a constellation of clinical findings as described by Gass and Blodi  in eitheAll eyes obtained SDOCT scans using the spectral domain Spectralis machine . 512 A-scans per line with a 30° scanning area and 25-line horizontal raster volume scans centered on the fovea were used for macular volumetric assessments. Additionally, a foveal-centered 12-line radial scan was analyzed for each eye. SDOCT scans with a quality score of > 20 were utilized for analysis and interpretation of the results. All images encompassing the macula were analyzed by independent observers from the respective centres (NR and ISA), who identified the following characteristics from inner to outer retina  vision for statistical analysis. Different SDOCT imaging features were described as numbers and percentages. Quantitative variables between the two groups were analysed using the Mann-Whitney U test for non-parametric data. Chi-square test was used to compare the categorical data between the two groups. Correlations between the different SDOCT biomarkers and visual acuity were analysed using the Spearman’s correlation test. The binary responses of the various SDOCT imaging features were converted to numerical values (0 = absent and 1 = present) for the purpose of studying correlation with visual acuity. Multiple variable linear regression analysis was performed between the visual acuity as the dependent variable and statistically significant SDOCT features on corelation matrix as independent variables. p values < 0.05 were considered statistically significant.All data were analysed using GraphPad Prism version 9.5.1 (733) for Windows, GraphPad Software, San Diego, California USA, The electronic medical record system identified a total of 1,806 type 2 MacTel patients. At the time of their type 2 MacTel diagnosis, 62 eyes of 32 (2%) of these MacTel cases were younger than 40 years of age. 90% (n = 56) of the eyes examined had visual complaints, such as blurred or wavy vision. The median and the mean age was 39 and 38.44 ± 1.795 years respectively. The youngest patient in the study was 34 years. 84% (n = 27) of the patients were female, and 50% (n = 16) were diabetic. In 30 (94%) of 32 young patients with type 2 MacTel, bilateral involvement was observed. Clinical and SDOCT data was available for 62 of 32 patients’ eyes. At baseline, the median logMAR visual acuity was 0.18 .Table Table For a better understanding of the SDOCT imaging characteristics, the eyes were divided into two groups: Group 1: non-proliferative type 2 MacTel (no SRNVM) and Group 2: proliferative type 2 Mactel (with SRNVM) Figs. . The visIn summary, the study revealed a significant predominance of females, with perifoveal hyperreflective MRL being the most frequently observed finding in OCT imaging. Additionally, the study identified hyperreflective RPC in the proliferative disease stage as the most relevant observation. Furthermore, it was observed that individuals with impaired visual acuity exhibited specific characteristics on SDOCT, such as the outward bending of inner retinal layers, RPC, subfoveal neurosensory detachment, and SRNVM. The current literature lacks a comprehensive description of the prevalence, clinical manifestations, and imaging characteristics of young individuals with type 2 MacTel.Type 2 MacTel is primarily a neurodegenerative disorder affecting the perifoveal region of the macula, characterized by microvascular alterations involving the deep retinal capillary plexus predominately . The etiIn its earliest stage, type 2 MacTel is typically asymptomatic, and it is frequently not diagnosed until patients are in their fifth to eighth decades of life and present with visual symptoms. Few population-based prevalence studies have been published in the scientific literature. The prevalence rate in the Melbourne Collaborative Cohort Study in Australia ranges from 0.0045 to 0.022%, while the prevalence rate in the American Beaver Dam Eye Study is estimated to be 0.1% . The estAbout 50% of the young patients with type 2 MacTel in our study had diabetes mellitus. Even in our previous publications, we had observed a high prevalence of diabetes in patients with type 2 MacTel , 11. TheIn our study cohort of young individuals with type 2 MacTel, the most frequently observed characteristics were loss of retinal transparency and the presence of perifoveal greying during clinical examination. Additionally, the presence of hyperreflective MRL, primarily in the temporal perifoveal region, was a common finding on SDOCT. These observations align with the findings reported in our previous publication on SDOCT findings in older individuals with type 2 MacTel . The ini90% (n = 56) of the eyes in the current study cohort were diagnosed with a non-proliferative stage of type 2 MacTel. These eyes presented with significantly better visual acuity than those with proliferative type 2 MacTel. In this study, the presence of RPC coincided with a proliferative stage of type 2 MacTel , which is an important finding. Leung et al. made comparable observations in their study and proposed modifying the current classification of type 2 MacTel based on pigment plaque characteristics . FurtherFurther differentiation of the SDOCT findings between those affecting the inner retinal layers and those affecting the outer retinal layers revealed that in our cohort of young type 2 MacTel patients, changes that predominantly involved the outer retinal layers were associated with significantly worse vision. Similar observations were made in our previous publication on SDOCT imaging characteristics in type 2 MacTel and their correlation with visual acuity . RegardlThere are several limitations related to our study. One significant constraint of this retrospective study is the lack of a control group consisting of individuals aged 40 years and above who have type 2 MacTel. Furthermore, the study solely provided a description of the SDOCT imaging outcomes during the initial presentation, without any reference to subsequent follow-up examinations. This study found a significant correlation between structural changes on SDOCT and visual acuity, with no other functional outcomes showing a similar association. To enhance the depth of the analysis, it would have been advantageous to incorporate additional important functional measures, including near vision, microperimetry changes, and multifocal electroretinography changes, in conjunction with the observed SDOCT changes. The investigation did not include an examination and correlation of additional outer retinal SDOCT observations, such as the discontinuity of the ELM, ellipsoid zone, and interdigitation zone, with visual acuity. Accurate identification of these findings on SDOCT, particularly during the proliferative stages of the disease, posed a significant challenge. The classification of SDOCT features based on their location and relationship to the fovea was not conducted in the study.Nevertheless, it is our belief that despite these constraints, our research brings attention to the frequency, clinical manifestations, and imaging characteristics of a specific group of individuals with type 2 MacTel who are below the age of 40 at the time of diagnosis. Future prospective studies are planned to investigate the symmetry of the disease, make comparisons with previous cases of type 2 MacTel, and examine longitudinal changes in SDOCT over a period of time.To summarize, type 2 MacTel is infrequent in individuals below the age of 40, often affecting both eyes, strongly linked to diabetes mellitus, and primarily impacts visual function during the later stages of the condition.


The composite foam effectively reduced residual strain, demonstrating the high resilience of the 3D-printed composite materials with a foam porous structure. The residual strain of the sample before foaming was >6% after a single cycle, and then gradually increased. The residual strain of the foamed samples is less than 5%. In addition, composite foam has high sensitivity and can monitor subtle pressure changes (0~40 kPa). The sensing performance of the composite foam was evaluated, and the current signal remained stable under different loading rates and small compression strains (2~5%). By using this highly resilient conductive composite material, a hierarchical shoe insole was designed that successfully detected human walking and running movements.Wearable flexible sensors with high sensitivity and wide detection range are applied in motion detection, medical diagnostic result and other fields, but poor resilience and hysteresis remain a challenge. In this study, a high-resilience foam sensor was prepared through a combination of additive manufacturing and green physical foaming method. The conductive filaments were prepared by using MWCNTs-modified TPU by the physical method of melt blending. Samples were prefabricated using the FFF printer and then saturated with CO Additive manufacturing or 3D printing is a technology based on the digital production of defined structures and geometric figures. It has been rapidly developed in several fields in recent years due to its advantages of controllable operation and high degree of design freedom. Compared with traditional molding methods, the selection of materials in the 3D printing process has more flexibility and functionality. For example, flexible electronic devices with customized structures can be designed through 3D printing by selecting flexible substrates with conductive materials. 3D printing can manufacture functional materials with complex macroscopic and controllable microscopic structures, which can greatly enhance the advantages of future biomedical sensing devices, including lower detection limits, higher sensitivity, larger sensing range and real-time diagnosis. Many studies have shown that flexible electronic devices show great potential applications in the fields of electronic skin, biomedicine and wearable electronic devices due to their high stretchability, high resilience and lightness ,2,3,4. A2, CO2) is not only friendly to the environment and leaves no chemical residue, but also has low cost and high efficiency. Physical foaming technology has achieved great success in preparing high-performance thermoplastic foam with microporous or nanoscale porous structure, reducing cell size to below 100 µm, thereby improving the mechanical properties of thermoplastic materials. Currently, there are three foaming methods: batch foaming; injection foaming; and extrusion foaming. Elastomers have hard segment (HS), low crystallinity, low modulus, excellent elasticity and a high gas diffusion rate. They exhibit unique cell nucleation, growth and cell structure stabilization during physical foaming, and exhibit post-foaming shrinkage behavior [The traditional foaming method is to add a chemical blowing agent (CBA) such as azodicarbonamide (AC) into the polymer and heat it to release gas during decomposition, which guides cell nucleation and growth. The size of the CBA and its dispersion in the matrix can hinder the reduction of cell size, and affect the foaming performance of the polymer. In addition, CBA can generate harmful substances during foaming and remain inside the foam product, so this is a trend towards using green foaming methods. Using physical blowing agents (PBA) for foaming  were obtained from Suzhou Tanfeng Graphene Technology Co., Ltd., Suzhou, China. High-purity CO2 gas (Purity > 99%) was obtained from Fuzhou Xinhang Industrial Gas Co., Fuzhou, China.Polyester-based TPU-65A with a density of 1.18 g/cmTo prepare high-quality FFF parts, the quality of the filament and the parameter settings during the printing process are key components of the process. Firstly, TPU masterbatches and MWCNTs are dried at 80 °C for 2 h, using the HAAKE-PolyLab twin-screw extruder to melt the co-blended masterbatch, and then the filament is extruded, collected by a downstream winder and pelletized . The pro2 gas, and the samples were saturated in CO2 gas for 30 min at a saturation pressure of 5 MPa. After finishing the saturation process, the samples were quickly transferred to the hot water bath at 80 °C for 30 s of the expansion process. Cell growth process is presented in According to the specific preparation methods reported in previous literature , the priThe dispersion of MWCNTs in the prepared filaments and the cell morphology of the 3D-printed samples after foaming were observed using a scanning electron microscope  and a benchtop scanning electron microscope , respectively. Thermogravimetric analysis was carried out on the instrument STA449F3 comprehensive thermal analyzer under a nitrogen atmosphere, the heating rate was 10 °C/min and the test temperature range was 30–800 °C. Analysis of TG is presented in 2 gas to form a polymer/gas homogeneous system. After the saturation, the cells are taken out by heating to induce cell nucleation and growth, and the sample showed obvious expansion. The mechanical properties of TPU and TPU/MWCNTs composite materials before and after foaming were evaluated by a tensile test. The printing density of tensile samples was 90%. The tensile stress-strain curve before foaming is shown in The TPU honeycomb model has light weight, high anisotropy and unprecedented mechanical properties, such as high energy absorption capacity, a high stiffness to density ratio, vibration characteristics and elastic wave propagation controllability ,29. TPU 0 = (I − I0)/I0. 0 increases from 3.37 to 16.60 in the compression strain range of 2–10%. Under small compression strains of 2–5%, ΔI/I0 can respond with stability, and the signal remains stable even with small strain changes, indicating that TPU/4MWCNTs composite conductive foam can not only detect small deformations, but also provide stable and reliable signal responses. Sensitivity is an important parameter to evaluate the sensing properties, and is defined as the relative change in the electrical signal divided by the slope of the applied pressure curve. −1 under 0~10 kPa higher than that reported in previous literature of PDMS foam compressive stress and sensitivity variation of low-stress states in shear and normal directions of three-dimensional interfacial graphene foam [−1 to 0.18 kPa−1; this shows that composite foam has high sensitivity and can monitor subtle pressure changes (0~40 kPa).Dynamic cyclic compression experiments were used to observe the changes of the current signals of TPU/4MWCNTs composite conductive foam, and upon further study of the sensing properties of TPU/4MWCNTs composite conductive foam, the relative current change is defined as ΔI/Isitivity . S increene foam ,36. As t2 foaming techniques. The insoles are embedded into the soles of sports shoes and connected to two wires as pressure sensors, enabling the monitoring of motion amplitude and frequency. The foam samples used in the experiment are non-toxic, and are fixed using insulating tape during the test to avoid direct contact with the human body. A digital multimeter was connected to record the current response ΔI/I0 of the porous foam pressure sensor in real time, and the change in human gait is analyzed by the changing ΔI/I0. 0 when walking is about 3, which is smaller than the ΔI/I0 when running (5~8). The ΔI/I0 signal variation curve while walking is relatively stable, while the signal variation curve during running is larger in magnitude because the whole body is in vigorous motion. In addition, the ΔI/I0 signal change time was shorter for walking than for running, indicating that the magnitude of motion could be distinguished by the frequency of ΔI/I0 signal change. These results confirm that customized porous foam insoles prepared by 3D printing and foam technology can not only monitor the change of human motion amplitude, but also improve the comfort of human wear [We further demonstrated the application of conductive foam as a wearable sensor in human motion monitoring. For example, porous foam elastic insoles that conform to the shape of the human foot were prepared using 3D printing and COman wear ,38.2 gas and foam at the same time when the material is extruded, in order to realize a one-step method to prepare thermoplastic foam with high design freedom.In summary, this work proposes a green method for preparing foam sensors with high resilience by combining fused filament fabrication and physical foaming techniques. The conductive filaments were prepared by using MWCNTs-modified TPU by the physical method of melt blending, which had good dispersion and interface compatibility. The foam prepared by high-pressure fluid technology has uniform pores, and can provide stable changes during deformation. The composite foam effectively reduces residual strain. The residual strain of TPU/MWCNTs composite material before foaming is greater than 6% after a single cycle, and gradually increases. However, the residual strain of the foaming samples is less than 5%. In addition, the composite foam has high sensitivity and can detect subtle pressure changes (0~40 kPa). The stability of the composite foam was evaluated, and it maintains a stable maximum stress of 40 kPa after 150 cycles at 10% strain. The sensing performance of the composite foam was evaluated, and a hierarchical shoe insole was designed using this high-resilience conductive composite material, which successfully detected human walking and running movements. By combining green physical foaming techniques, layered porous 3D-printed conductive materials could potentially be used to produce lightweight and customized wearable sensors. The batch foaming process in this work requires a good control of the time when the sample is taken out of the autoclave and put into the hot water bath after saturation, and there must be no human error. Therefore, in the future, a path can be designed at the nozzle to connect CO


Introduction: Neck pain is a common musculoskeletal condition frequently treated by physical therapists. The American Physical Therapy Association (APTA) published a clinical practice guideline (CPG) in 2008 with a revision in 2017 to improve the diagnosis and treatment of neck pain. One subset of neck pain in the CPG is “Neck Pain with Mobility Deficits,” also called mechanical neck pain. Little data exists on the adherence of physical therapists to the CPG-recommended treatments for neck pain as well as the outcomes associated with the utilization of the CPG. The purpose of this study is to examine both CPG treatment adherence and associated outcomes in patients treated for mechanical neck pain by physical therapists in the outpatient setting.Methods: Retrospective chart review of patients (n=224) who received physical therapy for neck pain between 2018 and 2022. Data ranges were chosen due to the publication of the CPG revision in 2017. Six interventions for mechanical neck pain from the CPG were examined: thoracic manipulation, cervical mobilization, transcutaneous electrical stimulation (TENS), dry needling, advice to stay active, and scapular resistance exercises. The exclusion criteria were a history of cervical spine surgery. Other data collected included age, sex, characteristics of the evaluating physical therapist, and the number of visits.Results: For CPG treatment adherence, 4.5% of patients received thoracic manipulation, 47.8% of patients received cervical mobilization, 12.5% of patients received TENS, 22.8% of patients received dry needling, 99.1% of patients received advice to stay active, and 89.3% of patients received scapular resistance exercises. There was no significant improvement in pain, range of motion (ROM), and function based on a number of CPG interventions used during the bout of physical therapy (p=0.17 to p=0.74). Patients who were evaluated by a physical therapist who was an Orthopedic Certified Specialist (OCS) were more likely to receive more interventions recommended by the CPG (p<0.01).Conclusion:CPG-recommended treatments are used with varying frequency by physical therapists when treating mechanical neck pain. Thoracic manipulation is rarely used while scapular resistance exercises are frequently used. There was no significant improvement in pain, ROM, or function based on the number of CPG-recommended treatments used during the bout of physical therapy. Neck pain is a common musculoskeletal pathology treated by physical therapists around the world ,2. Neck Common signs and symptoms of mechanical neck pain as listed in the CPG include central and/or unilateral neck pain, limited cervical range of motion (ROM), neck pain that is reproduced at end ranges of ROM, and restricted cervical and thoracic segmental mobility . This diOne recent study found that utilization of neck and low back CPGs was about 70%; however, utilization was not associated with final pain or disability in the study cohort . A greatThe current study is a retrospective chart review of 224 patients from multiple outpatient clinics within a single hospital system from 2018 to 2022. The current study was approved by the University Hospitals Institutional Review Board (IRB) under IRB approval #20220542. Patient charts were gathered by the University Hospitals Clinical Research Center based on having a diagnosis of neck pain (ICD-10 code M54.2) as well as a physical therapy evaluation procedure code . Inclusion criteria include receiving physical therapy for neck pain, being older than 18 years old, attending at minimum two sessions of physical therapy , and fitting best into the CPG category of “Neck Pain with Mobility Deficits” based on information in the patient chart. Exclusion criteria were a history of cervical spine surgery and fitting the CPG categories of “Neck Pain with Radiating Pain” or “Neck Pain with Movement Coordination Impairments.” From a total of 1500 patient charts, 224 patients were found to meet inclusion and exclusion criteria.Data collected include age, sex, number of physical therapy visits, Orthopedic Certified Specialist (OCS) status of the evaluating physical therapist, and the presence or absence of six CPG-recommended interventions for mechanical neck pain . Advice to stay active was defined as any home exercise program (HEP) given to the patient. Each of the six CPG interventions was recorded as present if the intervention was performed at least once during the entire bout of physical therapy. Furthermore, other outcome data include pain before and after physical therapy, total cervical rotation active ROM before and after physical therapy, and Neck Disability Index (NDI) score (listed as a percentage) before and after physical therapy. Total cervical rotation ROM was created by adding up a both right and left rotation to help reduce errors in measuring rotation ROM. Because most post-therapy measurements are obtained in the final session of therapy-a session which was missing for many patients who abruptly discontinued therapy-we also performed a subgroup analysis on outcomes for pain, ROM, and disability as expressed by the NDI to help get a more complete picture.Statistical analysis was performed using SPSS software version 29.0. Frequency counts were used to determining the usage of CPG interventions among the cohort. One-way ANOVA with Tukey posthoc testing was used to compare patients receiving two or less, three, or four or more CPG interventions. The t-test was used to compare the number of CPG interventions used in comparison to the OCS status of the treating physical therapist.Patients (n=224) in the current study had an average age  of 60.7 years 16.2 years) with 71.0% of patients (n=159) being female and 29.0% of patients (n=65) being male. Patients had an average (SD) number of PT visits of 7.1 visits (4.2 visits). Of the entire cohort, 76 patients (n=33.9%) had chronic neck pain, which we defined as pain lasting in duration equal to or longer than 180 days. For treatment selection, 4.5% of patients (n=10) received thoracic manipulation, 47.8% of patients (n=107) received cervical mobilization, 12.5% of patients (n=28) received TENS, 22.8% of patients (n=51) received dry needling, 99.1% of patients (n=222) received a HEP with advice to stay active, and 89.3% of patients (n=200) received scapular resistance exercises  received one intervention, 37.9% of patients (n=85) received two interventions, 41.5% of patients (n=93) received three interventions, 14.7% of patients (n=33) received four interventions, 2.7% of patients (n=6) received five interventions, and none of the patients received all six interventions , range of motion (n=96), and Neck Disability Index disability score (n=77). There was no significant difference in improvement in pain based on the number of CPG interventions used during the bout of PT (p=0.56). However, one-way ANOVA testing revealed a significant difference in the amount of PT visits used for pain outcomes (p<0.01). Patients who received four or more CPG interventions had significantly more visits than patients who received two or less CPG interventions during the bout of PT (p<0.01). There was no significant difference in improvement in ROM based on the number of CPG interventions used during the bout of PT (p=0.74). Furthermore, there was no significant difference in the amount of PT visits used based on the number of CPG interventions used (p=0.21). Finally, there was no significant difference in the improvement in disability per the Neck Disability Index based on the number of CPG interventions used during the bout of PT (p=0.17). However, patients who received four or more CPG interventions had significantly more PT visits with the same outcomes as compared to patients using three or two or less CPG interventions (p=0.02 and p<0.01).To further understand the different therapy utilization rates, patients were divided into groups depending on the OCS status of the treating physical therapist who did the evaluation. The OCS Group (n=16) and the Non-OCS group (n=174) had a significant difference in the amount of CPG interventions used (p<0.01), with the OCS group utilizing more CPG interventions (3.4 interventions compared to 2.7 interventions).Neck pain is a disabling condition that has received much attention in the literature in an effort to improve patient management via the creation and revision of a Neck Pain CPG by the APTA ,2. The cOur data showed that as the number of therapy visits increased, so too did the number of CPG interventions used and that neither of those variables was associated with improvement in pain. There was also a significant association between the increased number of physical therapy visits and the increased number of CPG-recommended treatments utilized during the bout of physical therapy. Depending on the outlook, the increased visits could be a positive or a negative attribute. Increased visits could indicate greater attendance to physical therapy visits because of higher quality physical therapy care, or it could indicate greater waste if the outcomes are the same, despite the increase in visits. Interestingly, that study by Beneciuk et al. found that the overall CPG treatment adherence rate that was relatively high (71.2%), which is contrary to the current study .There are several limitations of the current study. First, the study has a relatively small sample size from a single hospital system. Therefore, the results may not be generalizable to physical therapists across different regions. Furthermore, while the study included patients from multiple outpatient clinics, it is unknown how many physical therapists or physical therapist assistants participated in the treatment of the 224 patients in the study. Therefore, it is unknown if the problem is more widespread among physical therapists or just represents consistent poor adherence among a smaller number of physical therapists. It is also possible that some physical therapists are simply not aware of the current CPG. Strengths of the current study include the retrospective nature of the study compared to the surveys, which has been the usual way of assessing CPG adherence in the literature ,9,10. AcCPG interventions are used with varying frequency in patients treated by physical therapists for neck pain with mobility deficits. Thoracic manipulation is rarely used whereas advice to stay active and scapular resistance exercises are a common part of PT treatment for mechanical neck pain. The number of CPG interventions used during the treatment session did not impact outcomes for pain, ROM, and function. Furthermore, increased CPG intervention usage was associated with increased patient visits, despite no significant improvement in outcomes. Patients treated by an evaluating PT who had their OCS were more likely to be treated with more CPG interventions. More research is needed to determine impact of CPG on outcomes as well as reasons for adherence or non-adherence to CPG interventions.


Magnesium (Mg) has been intensively studied as a promising alternative material to inert metallic alloys for orthopedic fixation devices due to its biodegradable nature inside the body and its favorable biocompatibility. However, the low mechanical strength and rapid corrosion of Mg in physiological environments represent the main challenges for the development of Mg-based devices for orthopedic applications. A possible solution to these limitations is the incorporation of a small content of biocompatible nanoparticles into the Mg matrix to increase strength and possibly corrosion resistance of the resulting nanocomposites. In this work, the effect of adding boron nitride (BN) nanoparticles (0.5 and 1.5 vol.%) on the mechanical properties, corrosion behavior, and biocompatibility of Mg-based nanocomposites was investigated. The properties of the nanocomposites fabricated using powder metallurgy methods were assessed using microstructure analyses, microhardness, compression tests, in vitro corrosion, contact angle, and cytotoxicity tests. A significant increase in the microhardness, strength, and corrosion rates of Mg–BN nanocomposites was detected compared with those of pure Mg (0% BN). Crystalline surface post-corrosion byproducts were detected and identified via SEM, EDX, and XRD. Biocompatibility assessments showed that the incorporation of BN nanoparticles had no significant impact on the cytotoxicity of Mg and samples were hydrophilic based on the contact angle results. These results confirm that the addition of BN nanoparticles to the Mg matrix can increase strength and corrosion resistance without influencing cytotoxicity in vitro. Further investigation into the chemical behavior of nanocomposites in physiological environments is needed to determine the potential impact of corrosive byproducts. Surface treatments and formulation methods that would increase the viability of these materials in vivo are also needed. Magnesium (Mg), Mg-based alloys, and Mg-based composites represent a new class of biodegradable biomaterials that have been investigated for various orthopedic applications such as skeletal fixation hardware. The interest in Mg, compared with currently more prevalent inert metals such as stainless steels, titanium alloys, and cobalt–chromium alloys, is due to its biodegradable nature inside the body, allowing it to degrade after the completion of the bone healing process ,2,3. Thil- or d,l-lactic acid), poly(glycolic acid), and polycaprolactones (PCL) have also been of interest for orthopedic applications and have been FDA-approved as implant materials [Alternative biodegradable metals, such an iron (Fe) and zinc (Zn), are also candidates for the development of biodegradable orthopedic implants. Fe orthopedic implant materials as an abundant metal are associated with bone homeostasis. Additionally, despite having a higher strength, Fe has a higher elastic modulus compared with Mg and Zn and a slower degradation rate, which runs a higher risk of stress shielding with a corrosion behavior that is more like that of permanent implants ,18,19. Faterials ,24. The aterials ,25,26. Taterials ,28. TherSeveral strategies have been employed to overcome the limitations of Mg, such as surface modifications , alloyinTo this end, the objective of this study is to investigate the mechanical properties, corrosivity, and cytotoxicity of Mg nanocomposites reinforced with boron nitride (BN) nanoparticles (0.5 and 1.5 vol.% BN) for orthopedic fixation device applications. Microhardness and compression tests were performed to investigate the effect of the BN nanoparticles on the mechanical properties. In vitro electrochemical corrosion tests were performed to investigate the degradation and corrosion mechanism of the prepared nanocomposites. Scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX) were additionally used to characterize and visualize the surface of each experimental group. These data collectively assess the viability of Mg–BN nanocomposites as orthopedic implants and inform needed improvements.BN nanoparticles, 50 nm in diameter, were incorporated in Mg powder to synthesize BN–Mg nanocomposites of Mg–0.5%BN and Mg–1.5%BN vol.% through powder metallurgy and microwave-assisted rapid sintering methods ,42. Mg pThe microhardness test was conducted using a Shimadzu HMV-G21s Micro Vickers hardness tester . To prepare the samples for the microhardness test, the three sample types, Mg–0%BN, Mg–0.5%BN, and Mg–1.5%BN, were solidified in a polymer base using a Buehler Simplimet II mounting press . The nanocomposite samples solidified in a polymeric base were then polished using 100- to 3000-grit SiC sandpaper. The samples were then tested on a Shimadzu HMV-G21s Vickers microhardness tester at ambient temperature using a test load of 9.807 N, holding for 15 s, and indents were imaged at 10× magnification. Ten indents were performed on each of the tested groups. Additionally, cylindrical compression test specimens, prepared according to the ASTM E9-09 standard, were tested using an Instron-5569 universal testing machine. The test was conducted at 50% relative humidity and 20 °C.The density of the prepared samples was determined based on the Archimedes’ principle, using an MXBAOHENG MH-300A density meter. The measured density was then compared with the theoretical density and percentage porosity was calculated for each case. The theoretical density was determined based on the rule of mixture.Due to the importance of hydrophilicity in the interaction between orthopedic implants and surrounding osteoblasts and osteoclasts, the wettability of the coupons was determined by measuring the static contact angle three times on each side of the Mg–0%BN, Mg–0.5%BN, and Mg–1.5%BN coupon groups with four coupons of each sample using the sessile drop technique with a CAM PLUS MICRO contact angle meter  at ambient temperature. A micrometer syringe was used to dispense a droplet of 2–3 µL of distilled water or simulated body fluid (SBF) onto the surface of each coupon type. Measurements were replicated for water and SBF sanding samples immediately before analysis to obtain a more accurate contact angle. The resulting contact angle measured through projecting the droplet image on a protractor and an average contact angle was calculated for six different measurements of three similarly sized droplets on each side of the coupons, wiping the coupons clean with a Kim wipe after each measurement ,43,44,45corr). The potentiostat was programmed to send a DC potential varying from −0.25 to 0.25 V relative to the measured open circuit potential (OCV) through the electrodes at a scan rate of 1 mV/s while monitoring the current between electrodes that formed anodic and cathodic curves [corr (A/cm2) was calculated by dividing each x-axis value by the tested area of the sample (cm2). The icorr value was obtained from the graph using Tafel extrapolation and linear fitting approach [corr [The corrosion behavior of the prepared Mg nanocomposites was determined by conducting electrochemical corrosion tests in SBF. The SBF was optimized to contain ion concentrations approximating that of blood plasma and a fresh SBF was prepared for each respective corrosion test . Prior tc curves . From thapproach . The corch [corr ,51.2O for three sonication steps at five minutes each. Prior to cell culture, the samples were immersed in 70% ethanol for 5 min and sterilized in UV light for 10 min on each side [2. Attachment and seeding density were confirmed with the PrestoBlue Viability Assay  adhering to the protocol provided by the manufacturer, and increasing dilutions of coupon-leached αMEM were added to the cells. The seeded cells were cultured in the effluent-leached media along with controls grown with complete αMEM. The cell numbers were recorded with the PrestoBlue assay after culturing for 72 h by measuring fluorescence with an excitation wavelength of 530 with a bandwidth of 25 nm and a fluorescence wavelength of 590 with a bandwidth of 35 nm. Percent viabilities were calculated by dividing the final number of cells by the initial number and were normalized by dividing the resulting viability by the average percent viability of the control. Viabilities were imported into R where a two-way ANOVA test using a 95% confidence interval and a post hoc Dunnett test was performed on the resulting data. Weight loss post-incubation in media was measured to determine differences between interactions of nanocomposites and ultra-pure Mg in media.Sterilization protocols were performed according to the recommended sterilization of small Mg parts for cell culture experiments . The Mg ach side . The resach side . Coupon-ach side ,54. The A microstructural analysis of the prepared nanocomposites was performed to determine the effect of the BN addition on the microstructure. Prior to SEM analysis, non-corroded samples were polished to produce a mirror surface using a metallographic polishing and grinding machine with sandpapers of reducing grit sizes, etched in an acetic glycol solution composed of 20% acetic acid, 1% nitric acid, and 60% ethylene glycol for 3–5 s, and ultrasonically cleaned for 3 min immediately before SEM analysis .The surface of the prepared samples was characterized and imaged using scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX). Samples were prepared according to the sonication steps used prior to cytotoxicity, as previously mentioned. SEM images of the pure Mg samples and immersion samples were taken at magnifications of 500× to visualize the morphology of corroded and non-corroded samples. Separate samples were immersed in complete αMEM media for 72 h to determine corrosion byproducts under the conditions through which leached media was generated in the cytotoxicity studies. Point EDX spectra were detected to analyze the elemental composition of corrosion byproducts that formed on the surface of the samples and the surface composition of ultrasonically cleaned and etched samples. Data were collected at three points on the surface of coupons and the surface was scanned to analyze the overall composition. X-ray diffraction (XRD) was performed at a scan rate of 0.1°/s for samples before and after corrosion in αMEM media for 72 h. XRD diffractograms were developed through graphing detected intensity versus the 2 theta (°) angle and comparing the resulting data to known diffractograms using the X’Pert HighScore software’s built-in search-match algorithm containing elements detected in the previous EDX spectra analyses. Compounds with the highest score based on the search-match algorithm with background signal eliminated were accepted as candidates for corrosive byproducts of nanocomposite and pure Mg corrosion in media.p ≤ 0.05, p ≤ 0.01, p ≤ 0.001, and p ≤ 0.0001, respectively.Statistical significance between multiple groups was analyzed with either ANOVA tests if normality was established or a Kruskal–Wallis test due to a lack of data demonstrating normal distribution, as determined in a Shapiro–Wilk test. To determine differences between each group, a Dunnett post hoc was used for ANOVAs and a Dunn post hoc was performed if the Kruskal–Wallis was significant. A confidence interval of 95% was used to confirm significance. In the notation used in the figures, ns, *, **, ***, and **** represent no significance, Microstructure analyses were performed on cleaned and polished samples after etching in acetic glycol using SEM imaging. Samples imaged at 250× were taken immediately post-etching. The microhardness of the prepared Mg–BN nanocomposite and pure Mg samples was assessed. The average and standard deviation values obtained from the Vickers microhardness test were 40.1 ± 1.4, 41.1 ± 1.3, and 47.62 ± 1.6 HV for the pure Mg (Mg–0%BN), Mg–0.5%BN, and Mg–1.5%BN vol.% nanocomposite samples, respectively A. It canThe density of the nanocomposites and pure Mg samples was measured using a MXBAOHENG MH-300A density meter, which calculates density through Archimedes buoyancy principle. The densities obtained from the density meter were converted to porosity by computing the ratio of measured density to theoretical density and subtracting that ratio from one. The average relative density and density decreased in the line plot from Mg–0%BN to Mg–1.5%BN, as shown in The hydrophilicity of the nanocomposites was assessed by obtaining contact angle measurements for 6 drops on each side of the nanocomposite or pure Mg coupon, and a total of 12 drops were averaged for each sample. The sessile drop technique was used and, using a light source, we projected the image of the drop on a backboard containing a goniometer to determine contact angle. The hydrophilicity assessment using the contact angle test showed an average contact angle of 125.9 ± 11.2°, 107.6 ± 16.1°, and 124.4 ± 10.7°, for the pure Mg, Mg–0.5%BN, and Mg–1.5%BN samples, respectively, with distilled water on non-sanded surfaces see . An ANOVle group . The wet-sanding . The reaThe corrosion current densities of the pure Mg (Mg–0%BN), Mg–0.5%BN, and Mg–1.5%BN samples were obtained by extrapolating the anodic and cathodic curves generated by potentiodynamic polarization (PDP) tests. Corrosion current densities based on the Tafel extrapolation method can be used as an indicator for the corrosion rates and a benchmark of the corrosion resistance. Higher current densities generally mean higher corrosion rates and, hence, less corrosion resistance. Corrosion current densities determined through electrochemical testing, see The properties of Mg–BN nanocomposites are summarized in p > 0.05), suggesting that BN at low vol.% does not significantly impact the cytotoxicity of Mg  and the ultra-pure control (hot-rolling). These data suggest that increased microhardness and strength is not entirely indicative of increased corrosion resistance. It has been previously demonstrated that a nickel–tungsten alloy supplemented with increasing concentrations of BN nanoparticles showed a decreased corrosion resistance in electrochemical tests followed by a decrease in resistance upon further increases in BN .The results of the biocompatibility studies measuring the cytotoxicity of nanocomposite and ultra-pure Mg-leached media demonstrate that BN nanoparticle addition does not confer cytotoxic effects. At the dilutions of 6× and 10×, the average% viabilities were above 70% normalized viability compared with non-treatment. This indicates that 70% of cells were retained post-treatment with leached media for 24 h in all groups. Because there was no statistical significance between nanocomposite and ultra-pure Mg cytotoxicity, we can conclude that BN nanoparticles do not confer cytotoxic effects, but also do not enhance the cytocompatibility. Long-term assessments of viability overtime, however, need to be investigated to further support this conclusion. In vitro coupon weight-loss in media after 72 h suggested that longer corrosion times are required to determine the corrosive variation between Mg–0.5%BN, Mg–1.5%BN, and ultra-pure Mg due to inconsistent results. This assessment of weight loss to estimate corrosion rate may be inaccurate during short corrosion periods, as these data are inconsistent with SBF corrosion demonstrated in the literature. These data also indicate that surface coatings enhancing cytocompatibility and increasing corrosion resistance are necessary for in vivo applications.Surface characterization post-corrosion in media showed that nanocomposites appear to oxidize faster than ultra-pure Mg in ultrasonically cleaned samples based on byproducts appearing on SEM images of nanocomposites alone. Furthermore, carbon and oxygen content significantly decreased in corroded nanocomposites based on EDX spectra results. Further investigation with XRD revealed that this oxygenation can be attributed to magnesium oxide (1.5 BN) and magnesium peroxide (0.5 BN) present on the surface. However, there is little explanation for the increase in carbon content observed in the EDX analyses.The use of low contents (0.5 vol.% and 1.5 vol.%) of BN particles to strengthen the Mg matrix was examined for mechanical properties, corrosion behavior, and cytotoxic effects for skeletal fixation hardware applications. In terms of the distortion of grains and grain boundaries due to the hot extrusion process, the microstructure of Mg–BN nanocomposites does not appear to be impacted by the addition of BN compared to pure Mg. The addition of nanocomposite BN particles, however, increased the strength and microhardness of the Mg matrix by limiting the dislocation movement and twining, which is critical due to the low strength of pure Mg. The addition of BN also increased the corrosion resistance in electrochemical tests compared with 0% BN–Mg synthesized in a similar manner. The Mg–BN nanocomposite samples showed similar hydrophilic contact angles with SBF and in vitro cytotoxicity levels to those for the ultra-pure Mg when coupons leached in α-MEM media were exposed to MC3T3-E1 cells. The EDX and XRD data revealed the identity of the byproducts of corrosion in media to be primarily oxidated Mg with a more crystalline appearance in the Mg–BN nanocomposite samples. The impact of this behavior requires further investigation to determine the nature of this reaction in media. Collectively, these data suggest that the strengthening of the Mg matrix improved electrochemical corrosion behavior. The contact angle analysis indicates that surface modification  is essential to protect the Mg from surface oxidation, which dramatically increases hydrophobicity based on contact angle. Further, coatings to reduce immersion corrosion rates are also required to retain implant function for orthopedic applications. Further investigation of the interaction of BN nanocomposites with a biological environment and improvements in synthesis methods and surface modifications is needed.


Homonymous hemianopsia (HH) corresponds to vision loss in one hemi-field secondary to retro-chiasmal injury. Patients with HH experience difficulties in scanning and orientation in their environment. Near vision daily activities such as reading can also be impaired. There is an unmet need for standardized vision rehabilitation protocols for HH. We investigated the effectiveness of biofeedback training (BT), used for vision rehabilitation in patients with central vision loss, in individuals with HH.In this prospective pilot pre/post study, 12 participants, with HH consecutive to brain injury, performed 5 weekly BT sessions for 20 min each under supervision using the Macular Integrity Assessment microperimeter. BT consisted of relocation of the retinal locus 1–4° toward the blind hemi-field. Outcomes measured post-BT were paracentral retinal sensitivity, visual acuity (near vision), fixation stability, contrast sensitivity, reading speed, and visual functioning questionnaire. Statistical analysis was performed using Bayesian paired t-tests.Paracentral retinal sensitivity significantly increased by 2.7 ± 0.9 dB in the treated eye in 9/11 of the participants. Significant improvements with medium-to-large effect size were observed for fixation stability (8/12 participants), contrast sensitivity (6/12 participants) and near vision visual acuity (10/12 participants). Reading speed increased by 32.5 ± 32.4 words per minute in 10/11 participants. Quality of vision scores improved significantly with large effect size for visual ability, visual information and mobility.BT led to encouraging improvements in visual functions and functional vision in individuals with HH. Further confirmation with larger trials is required. Patients with brain injury frequently suffer from homonymous hemianopsia (HH), defined as vision loss in one vertical hemi-field secondary to a retro-chiasmal lesion –4. In HHCentral vision can also be affected in hemianopsia due to a parafoveal field loss with splitting of fixation and poor eye movements leading to reading deficit. Left-to-right readers with a right HH have particularly impaired reading abilities. For efficient reading, three to four letters to the left and seven to 11 letters to the right of fixation must be seen , 6. PatiPatients with HH naturally develop oculomotor strategies to compensate for visual field loss, however, these strategies are often suboptimal and oculomotor control is impaired . To scanBiofeedback training (BT) is a compensatory rehabilitation technique that emerged three decades ago and has been used in various fields of medicine, including ophthalmology , 12. BT The goal of this study was to use BT in an innovative way. Using our experience from different pathologies, we proposed a BT protocol specific to HH with the automated MAIA microperimeter. One of the symptoms in hemianopia is the loss of parafoveal visual references, causing oculomotor dysfunction. We hypothesized that relocating the fixation locus of the patients to an area with a larger span would improve oculomotor control and increase visual performance. A retinal locus with higher sensitivity and larger visual span was used on the seeing hemi-retina, or blind hemifield. A maximum of 4° of fixation relocation was allowed, in order to keep the better visual acuity from the parafoveal retina. This method would eliminate the splitting of fixation from the hemianopsia while improving the oculomotor function. BT is a technique that primarily increases the fixation stability and oculomotor control, perpetuating the benefit from field relocation.The study was designed as a prospective, pilot, interventional pre/post, case series. Twelve patients were recruited from the Low Vision Clinic at the Toronto Western Hospital, University of Toronto, Canada. Criteria for inclusion were diagnosis of hemianopsia based on visual fields, brain injury from various etiologies, age between 18 and 90 years old, and ability to follow the visual, auditory stimuli, and training instructions. Exclusion criteria were previous treatment for low vision rehabilitation, significant underlying ocular pathology not related to the hemianopsia physiopathology, and cognitive impairment that prevents an adequate test and training performance. Patients had one baseline visit 1 (V1), five BT visits (V2-6), 1 week follow up visit (V7) and 1 month follow up visit (V8).Twelve patients  with hemClinicalTrials.gov (NCT05397873A). Data was collected from July 2021 to November 2022. Written informed consent was obtained from all patients.The study was approved by the University Health Network Research Ethics Board, reference number 20-5618  and registered at During V1, paracentral retinal sensitivity or PRS  was assessed using the Macular Integrity Assessment (MAIA) microperimeter . Fixation stability (FS) was calculated by the MAIA software as a 63% bivariate contour ellipse area (BCEA 63%). A standard LED fixation target consisting of a small red circle of about 0.76° diameter was presented for microperimetry and fixation tests. To account for learning effect, FS was measured two times and the first results were disregarded. Monocular Best Corrected Visual Acuity (BCVA) was obtained for distance with Early Treatment Diabetic Retinopathy Study (ETDRS) charts at 4 m and for near vision with the 100% contrast Colenbrander continuous print chart. Reading speed was measured using the Minnesota Low Vision Reading Test application  . QualityBT involved luminous stimulation with auditory feedback performed on the MAIA microperimeter, biofeedback module  would increase frequency progressively, until the TRL was reached, and the auditory feedback would change to a continuous pattern. At this moment, a luminous white dot appeared at the TRL to produce the bimodal stimulation. During this task, the participant would actively control the eye movements and repeat consecutively this fixation in order to exercise the oculomotor control toward and at the TRL.From V2 to V6, BT was performed weekly for 5 weeks. Each BT session was 20 min long representing a total of 100 min. Pauses were allowed whenever needed.Data analysis was based on descriptive statistics including, a measure of central tendency (median) and dispersion . Eventual missing data were discounted from baseline and outcomes measures. Statistical comparisons between populations were performed by Bayesian paired t-tests (strength of evidence for H1 and Cohen’s d) using JASP software.+0 = 65.5, error % = 8.14e-7, d = 1.15, 95%CI ] after treatment in the treated eye, indicating a restoration of visual perception at the border of the blind hemifield ] after treatment ] after treatment in 8/12 patients ] after 5 weeks of BT ] after BT in 6/12 patients ] after treatment ] in 10/11 patients (P11 could not perform the test). Comparisons for individual sub-categories indicated significant improvement in all sub-sections from the VA-LV-VFQ 48 questionnaire  when comparing baseline and after treatment, however, a placebo effect cannot be excluded.Overall subjective quality of vision scores  reportedThe PRL was trained to relocate 2.0 ± 0.4° toward the blind hemifield on the retina. Measures post-treatment indicated a relocation of the PRL 0.14 ± 0.5° within the blind hemifield .Our study showed significant improvement in paracentral retinal sensitivity, fixation stability, contrast sensitivity, near vision, reading speed, and subjective visual functioning. The treatment consisted of a weekly BT session (20 min) for 5 weeks with audio-luminous stimuli on the MAIA microperimeter. BT was delivered after the critical healing phase post brain-injury (exception for P5 treated 2.5 months post-stroke).Strong and moderate evidence for increased PRS within the central 4° horizontal and 20° vertical of the new PRL were observed in the treated and fellow eyes, respectively. PRS measured by automated microperimetry (MAIA C10-2 program) is controlled for the loss of fixation, therefore, such improvement of the PRS with medium to large effect size strongly suggests visual field relocation at the border of the blind hemi-field. As the seeing hemi-retina is relocated to the center of the new test, the MAIA would capture the PRS from a better retinal area, representing a better use of the visual functions.The recovery of visual perception at the border of the scotoma has been observed in individuals with hemianopsia using field restitution rehabilitation approaches, although it requires significantly longer duration of stimulation, typically for several months, representing hundreds of hours of stimulation , 24. OthThe fast functional visual improvements when compared to the traditional compensatory therapies might be the consequence of the combination of auditory biofeedback and visual stimulation, reinforcing the training effect of new PRL relocation through multisensory processing .Fixation stability significantly improved in accordance with the expected effect of BT which trains the patients to use a new PRL through oculomotor control for activities of daily living . SimilarContrast sensitivity at 1 cycle/° also improved. This could be the consequence of the improvements observed in paracentral fields sensitivity and fixation stability. Such increase in contrast sensitivity was observed in other studies using high-contrast visual stimulation , 27.Parafoveal retinal sensitivity, fixation stability and contrast sensitivity are essential features for proper reading . AccordiOverall subjective patient-reported visual function strongly improved, corroborating the results observed with visual function and functional vision outcomes. More specifically, the visual ability and visual mobility subgroups showed the highest effect size, suggesting that the patients show improved navigation and orientation. Consistent with the medium size of improvement in reading speed, the patient-reported score of reading ability also moderately increased after BT.Our results are unlikely due to a learning/adaptation effect of the visual tests as baseline and after treatment assessments at the clinic were separated by a minimum of 5 weeks, above the learning effect time window shown to last for up to 1 week . AudioviThe audiovisual sensory BT is a therapy used in low vision for more than 10 years, showing good results for near and distance vision in individuals with macular degeneration and other low vision conditions –19. A liThe raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by University Health Network Research Ethics Board. The patients/participants provided their written informed consent to participate in this study.MMi is the first author, current clinical fellow seeing the patients and contributing to the manuscript preparation. YP worked for 2 years as a clinical fellow seeing patients for the project, obtaining consents and questionnaires. AS worked as a technician and optometrist assessing the patients and obtaining consents and questionnaires. MMa is an optometrist and occupational therapist and was involved in the design of the study and recruitment of patients. SM is the professor involved in the design of the study and manuscript confection. MR is the co-senior author involved in design, statistical analysis, and manuscript preparation. MD-N idealized the study, was the principal investigator supervising and participating in all activities, including manuscript preparation. All authors contributed to the article and approved the submitted version.This work was supported by UHN Foundation (MR).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


L* value and an increasing ΔE value. The application of principal component analysis can effectively distinguish the significant effect of FID on the volatile odor profiles of shiitake mushrooms. Compared to raw shiitake mushrooms, FID treatment has endowed samples with a greater variety of volatile compounds. After processing with FID, there have been increases in volatile components such as sulfur compounds, acids, nitrogen compounds, and aldehydes, while volatile components like alcohols, ketones, and hydrocarbons have shown decreases.The effects of far infrared radiation drying (FID) on physical properties  and volatile odor characteristics (volatile odor profile distinction and volatile compounds) of shiitake mushrooms were evaluated in this study. During the FID, the drying time decreased with the increase in drying temperature, and it had a less significant effect in the lower temperature range. The increase in drying temperature led to increasing shrinkage and collapse in the microstructure, resulting in a decreased rehydration rate and highlighting the influence of microstructure characteristics on macroscopic properties. Higher drying temperatures employed in the FID process were found to be associated with a decreasing  Lentinula edodes) are a highly cultivated and widely consumed species of edible fungus worldwide [Shiitake mushrooms  and the volatile odor characteristics (volatile odor profile distinction and volatile compounds) of shiitake mushrooms are crucial quality attributes that determine consumer acceptance and market value. The microstructural characteristics of shiitake mushrooms after drying are closely related to shrinkage and rehydration capacity, directly determining the appearance of the product after rehydration. The distinct odor characteristics of shiitake mushrooms are the result of the combined action of various volatile compounds, including alcohols, ketones, aldehydes, acids, and sulfur compounds. Xu et al. investigated the relationship between the pre-drying temperature and overall quality  of dried shiitake mushrooms . The stuThis present study aimed to explore the impacts of far infrared radiation drying on the physical properties  and the volatile odor characteristics (volatile odor profile distinction and volatile compounds) of shiitake mushrooms. This study aimed to provide theoretical evidence for the industrial far infrared radiation drying of shiitake mushrooms.Raw shiitake mushrooms were sourced from a local market . The shiitake mushroom samples, after removing stipites, were approximately circular with similar sizes (average radius was 3.2 ± 0.4 cm). The thickness of shiitake mushroom pilei was 1.1 ± 0.2 cm. The average initial moisture content of the raw shiitake mushrooms was 87.31 ± 0.34% on a wet basis or 6.67~7.09 kg/kg on a dry basis.Raw shiitake mushrooms (500 g) were placed in a single layer on trays. Samples were placed in the shade and attention was given to flipping and weighting them every four hours during the day. The average temperature recorded was 25 ± 5 °C, while the relative humidity averaged 40 ± 10%. The SD process continued for approximately four days until the samples reached a constant final weight.2, was designed to emit thermal radiation. The adjustable temperature range was from 25 °C to 90 °C, with air flow rate of 1.5 m/s. The temperature sensor was positioned parallel to the surface of the samples for collecting the thermocouple signals. The collected thermocouple signal was utilized by the proportional integral derivative controller to regulate the operation of the heating panel. During the drying process, the sample tray was periodically taken out at 60 min intervals, and was swiftly weighed on a digital balance with an accuracy of ±0.01 g  and then was returned to the chamber. The drying process persisted until the moisture content of the sample reached 13% on a wet basis. After cooling to room temperature, the dried samples were packed into heat-sealed bags for subsequent measurement.Based on the current situation and previous studies ,14 on shM0 is the initial moisture content; tM is moisture content at t during drying (kg/kg on a dry basis); and eM is the equilibrium moisture content with a value of approximately 0.05 kg/kg on a dry basis, which is comparatively lower than tM and M0 in this test. Thus, Equation (1) can be simplified as follows [The moisture ratio (MR) of shiitake mushrooms during the thin–layer drying experiments is determined using the following equation :(1)MR=Mt follows :(2)MR=MtV1) and after drying (V2), and the shrinkage ratio was calculated using the following formula:The shrinkage ratio (SR) of the dried shiitake mushrooms was determined according to Xiao et al. , with slThe rehydration ratio (RR) of the dried shiitake mushrooms was determined using the method of Sun et al. , with slScanning electron microscopy  was used to observe the microstructure of shiitake mushroom pilei under various drying conditions . The thiL*, a*, and b* were directly measured with a colorimeter , and the CIELAB color space diagram was utilized to represent sample colors following the previously described method [E) was calculated using Equation (5) [The color parameters d method . The illtion (5) .(5)ΔE=LL0, a0, and b0. Additionally, L*, a*, and b* were used to quantify the lightness, the redness/greenness, and the yellowness/blueness of the dried samples, respectively.The reference values for raw shiitake mushrooms were The volatile odor characteristics of shiitake mushroom pilei under different drying conditions were distinguished with electronic nose , which was equipped with 10 sensors  capable of detecting different compounds . Before The volatile compounds were measured using the headspace solid-phase microextraction gas chromatography mass spectrometry (HS-SPME-GC-MS) described by Chen et al. , with slVolatile compounds were analyzed using an Agilent 7890B GC coupled with an Agilent 5977B MS. The GC system was equipped with an HP-5MS fused silica capillary column . The GC conditions were set as follows: helium was used as the carrier gas with a fixed flow rate of 1 mL/min. The injector temperature was set at 250 °C. The initial oven temperature programming was set at 35 °C for 3 min, then ramped at 3 °C/min to 150 °C, maintained for 1 min, and finally ramped at 5 °C/min to 220 °C, and held for 2 min. The ionization source temperature was set at 230 °C. The mass spectrometry (MS) analysis was performed using the electron impact mode at 70 eV, covering a range of 30 amu to 395 amu. Volatile compounds were identified with a database (NIST17.L).Each test group was conducted in triplicate, and the mean value was obtained. Three samples were randomly selected from each test group for analysis of physical properties and volatile odor characteristics. The experimental data from the drying process were analyzed using Excel 2013. The significance of the mean difference was evaluated using one-way analysis of variance (ANOVA) with Duncan’s new multiple range test. The significance level was set at 0.05, and the analysis was performed using SPSS 22.0 software.Phaleria macrocarpa (Mahkota Dewa) fruits [To explore the effects of the FID temperature  on the drying kinetics of shiitake mushrooms, the moisture ratio (MR) curves versus the drying time of shiitake mushrooms at different FID temperatures are presented in ) fruits  and by X) fruits . The penDuring the process of drying, food materials experience alterations in volume, which can lead to either shrinkage or expansion, accompanied by the loss of water. The actual shrinkage images, shrinkage ratio (SR), and rehydration ratio (RR) of shiitake mushrooms under various drying conditions are presented in SD samples exhibit lower SR compared to FID. The phenomenon can be attributed to the longer drying time, allowing the product more time to undergo shrinkage . As the Generally, SD samples exhibit a higher RR than FID counterparts except FID 50 °C. This phenomenon can potentially be attributed to the moisture migration process during FID. From Microstructural characterization plays a vital role in evaluating the quality of final products. The microstructure of shiitake mushrooms’ longitudinal sections dried at various temperatures during FID were characterized using scanning electron microscopy (SEM) at a magnification level of 200-fold in L*, a*, b*, and ΔE of samples under different FID temperatures are displayed in L* value), redness , yellowness , and a higher total color difference  compared to the raw sample, which is consistent with previous studies [p < 0.05) were observed in the L*, a*, b*, and ΔE values among the different FID temperatures. Higher drying temperatures employed in the FID process were found to be associated with a decreasing L* value and an increasing ΔE value. This result can be primarily attributed to the occurrence of the nonenzymatic Maillard reaction, known for promoting the formation of brown pigments. The Maillard reaction is influenced by multiple factors, such as pH, moisture content, temperature, and the ratio of amino acids to reducing sugars [The surface color of shiitake mushrooms is a crucial quality indicator that determines consumer acceptance and market value . The col studies . Moreoveg sugars . This wag sugars , who fouThe electronic nose rapidly captures a wide range of volatile components and sensory attributes, simulating the human olfactory system through a sensor array system . It has The relationship between samples and electronic nose sensors was further elucidated through the application of PCA analysis, with the results presented in To further distinguish the profiles of the samples subjected to FID and SD, the electronic nose information of raw samples was excluded, and PCA analysis was performed, as depicted in The characteristic aromas of food are primarily the result of volatile compounds, which are a prominent characteristic of shiitake mushrooms and have a significant impact on consumer preferences . To inveThe alcohols (63.69%), S-compounds (28.28%), and ketones (4.70%) were the main volatile flavor components in raw shiitake mushrooms, which was consistent with previous studies . The maiThe content of S-compounds, acids, N-compounds, and aldehyde exhibited varying degrees of increase after the FID treatment shown in L* value and an increase in the ΔE value. A PCA analysis can effectively distinguish the significant impact of FID on the volatile odor profiles of shiitake mushrooms. FID treatment enriched the samples with a greater variety of volatile compounds compared to raw shiitake mushrooms. Following FID processing, there was an increase in volatile components such as S-compounds, acids, N-compounds, and aldehydes, while volatile components like alcohols, ketones, and hydrocarbons decreased.This study investigated the effects of far infrared radiation drying on the drying kinetics and quality characteristics  of shiitake mushrooms. The drying time decreases with the increase in drying temperature in FID, and it has a smaller effect in the lower temperature range. The drying time decreases with increasing FID temperature, and the impact is less significant at lower temperatures. Increasing the drying temperature results in the shrinkage and collapse of the microstructure, reducing the rehydration rate, and emphasizing the impact of microstructure characteristics on macroscopic properties. The application of higher drying temperatures in the FID process is linked to a decrease in the This study evaluated the effects of far infrared radiation drying on the physical properties and volatile odor characteristics of shiitake mushrooms. In future research, volatile and non-volatile flavor compounds should be studied to reveal their contributions to flavor during drying. Additionally, further exploration is needed to understand the impact of water migration processes, water status, and changes in cellular structure on flavor formation.