Risk Factors Associated with Chemotherapy-Induced Nausea and Vomiting Among Women with Breast Cancer Receiving Highly Emetogenic Chemotherapy: Individual Patient-Based Analysis of Three Prospective Antiemetic Trials.

Purpose: Although risk factors related to chemotherapy-induced nausea and vomiting (CINV) have been identified in previous studies, only a few studies have evaluated the risk factors associated with contemporary antiemetic prophylaxis, including olanzapine/aprepitant- or NEPA-containing regimens. This study aimed to identify the risk factors associated with CINV development in Chinese breast cancer patients receiving doxorubicin and cyclophosphamide chemotherapy. Methods: Data from 304 patients enrolled in 3 previously reported prospective antiemetic studies were included. Multivariate logistic regression models were used to predict risk factors associated with CINV occurrence. Additionally, the likelihood of treatment failure in relation to the number of risk factors in individual patients was evaluated. Results: Multivariate analysis of the entire study group revealed that obesity status (defined as body mass index/= 25.0 kg/m2) and the use of olanzapine/aprepitant- or NEPA-containing anti-emetic regimens were associated with a high likelihood, while a history of motion sickness was associated with a lower likelihood, complete response (CR), and "no nausea" in the overall phase. A history of vomiting during pregnancy was also associated with a lower likelihood of an overall CR. Patients with an increasing number of risk factors had a higher likelihood of treatment failure and shorter time to first vomiting. Those who did not achieve CR and "no nausea" in the first cycle were less likely to achieve these parameters in the subsequent cycle of chemotherapy. Conclusion: The present study confirmed previously reported risk factors for CINV in Chinese breast cancer patients receiving doxorubicin and cyclophosphamide. Further optimization of CINV control is required for patients with identifiable risk factors; olanzapine/aprepitant- or NEPA- containing prophylaxis are the preferred contemporary anti-emetics regimens for Chinese breast cancer patients undergoing doxorubicin and cyclophosphamide chemotherapy.

Salmonella exploits membrane reservoirs for invasion of host cells.

Salmonella utilizes a type 3 secretion system to translocate virulence proteins (effectors) into host cells during infection1. The effectors modulate host cell machinery to drive uptake of the bacteria into vacuoles, where they can establish an intracellular replicative niche. A remarkable feature of Salmonella invasion is the formation of actin-rich protuberances (ruffles) on the host cell surface that contribute to bacterial uptake. However, the membrane source for ruffle formation and how these bacteria regulate membrane mobilization within host cells remains unclear. Here, we show that Salmonella exploits membrane reservoirs for the generation of invasion ruffles. The reservoirs are pre-existing tubular compartments associated with the plasma membrane (PM) and are formed through the activity of RAB10 GTPase. Under normal growth conditions, membrane reservoirs contribute to PM homeostasis and are preloaded with the exocyst subunit EXOC2. During Salmonella invasion, the bacterial effectors SipC, SopE2, and SopB recruit exocyst subunits from membrane reservoirs and other cellular compartments, thereby allowing exocyst complex assembly and membrane delivery required for bacterial uptake. Our findings reveal an important role for RAB10 in the establishment of membrane reservoirs and the mechanisms by which Salmonella can exploit these compartments during host cell invasion.

P-TDHM: Open-source portable telecentric digital holographic microscope.

We present the design of a low-cost, portable telecentric digital holographic microscope (P-TDHM) that utilizes off-the-shelf components. We describe the system's hardware and software elements and evaluate its performance by imaging samples ranging from nano-printed targets to live HeLa cells, HEK293 cells, and Dolichospermum via both in-line and off-axis modes. Our results demonstrate that the system can acquire high quality quantitative phase images with nanometer axial and sub-micron lateral resolution in a small form factor, making it a promising candidate for resource-limited settings and remote locations. Our design represents a significant step forward in making telecentric digital holographic microscopy accessible and affordable to the broader community.

Protocol for evaluating mitochondrial morphology changes in response to CCCP-induced stress through open-source image processing software.

Mitochondrial morphology is an indicator of cellular health and function; however, its quantification and categorization into different subclasses is a complicated process. Here, we present a protocol for mitochondrial morphology quantification in the presence and absence of carbonyl cyanide m-chlorophenyl hydrazone stress. We describe steps for the preparation of cells for immunofluorescence microscopy, staining, and morphology quantification. The quantification protocol generates an aspect ratio that helps to categorize mitochondria into two clear subclasses. For complete details on the use and execution of this protocol, please refer to Nag et al.1.

The design, synthesis, and inhibition of Clostridioides difficile spore germination by acyclic and bicyclic tertiary amide analogs of cholate.

Clostridioides difficile infection (CDI) is a major identifiable cause of antibiotic-associated diarrhea. In our previous study (J. Med. Chem., 2018, 61, 6759-6778), we have identified N-phenyl-cholan-24-amide as a potent inhibitor of spore germination. The most potent compounds in our previous work are N-arylamides. We were interested in the role that the conformation of the amide plays in activity. Previous research has shown that secondary N-arylamides exist exclusively in the coplanar trans conformation while tertiary N-methyl-N-arylamides exist in a non-planar, cis conformation. The N-methyl-N-phenyl-cholan-24-amide was 17-fold less active compared to the parent compounds suggesting the importance of the orientation of the phenyl ring. To lock the phenyl ring into a trans conformation, cyclic tertiary amides were prepared. Indoline and quinoline cholan-24-amides were both inhibitors of spore germination; however, the indoline analogs were most potent. Isoindoline and isoquinoline amides were inactive. We found that the simple indoline derivative gave an IC50 value of 1 µM, while the 5'-fluoro-substituted compound (5d) possessed an IC50 of 400 nM. To our knowledge, 5d is the most potent known spore germination inhibitor described to date. Taken together, our results indicate that the trans, coplanar conformation of the phenyl ring is required for potent inhibition.

PGAM5 is an MFN2 phosphatase that plays an essential role in the regulation of mitochondrial dynamics.

Mitochondrial morphology is regulated by the post-translational modifications of the dynamin family GTPase proteins including mitofusin 1 (MFN1), MFN2, and dynamin-related protein 1 (DRP1). Mitochondrial phosphatase phosphoglycerate mutase 5 (PGAM5) is emerging as a regulator of these post-translational modifications; however, its precise role in the regulation of mitochondrial morphology is unknown. We show that PGAM5 interacts with MFN2 and DRP1 in a stress-sensitive manner. PGAM5 regulates MFN2 phosphorylation and consequently protects it from ubiquitination and degradation. Further, phosphorylation and dephosphorylation modification of MFN2 regulates its fusion ability. Phosphorylation enhances fission and degradation, whereas dephosphorylation enhances fusion. PGAM5 dephosphorylates MFN2 to promote mitochondrial network formation. Further, using a Drosophila genetic model, we demonstrate that the MFN2 homolog Marf and dPGAM5 are in the same biological pathway. Our results identify MFN2 dephosphorylation as a regulator of mitochondrial fusion and PGAM5 as an MFN2 phosphatase.

Mechanism of germination inhibition of Clostridioides difficile spores by an aniline substituted cholate derivative (CaPA).

Clostridioides difficile infection (CDI) is the major identifiable cause of antibiotic-associated diarrhea and has been declared an urgent threat by the CDC. C. difficile forms dormant and resistant spores that serve as infectious vehicles for CDI. To cause disease, C. difficile spores recognize taurocholate and glycine to trigger the germination process. In contrast to other sporulating bacteria, C. difficile spores are postulated to use a protease complex, CspABC, to recognize its germinants. Since spore germination is required for infection, we have developed anti-germination approaches for CDI prophylaxis. Previously, the bile salt analog CaPA (an aniline-substituted cholic acid) was shown to block spore germination and protect rodents from CDI caused by multiple C. difficile strains and isolates. In this study, we found that CaPA is an alternative substrate inhibitor of C. difficile spore germination. By competing with taurocholate for binding, CaPA delays C. difficile spore germination and reduces spore viability, thus diminishing the number of outgrowing vegetative bacteria. We hypothesize that the reduction of toxin-producing bacterial burden explains CaPA's protective activity against murine CDI. Previous data combined with our results suggests that CaPA binds tightly to C. difficile spores in a CspC-dependent manner and irreversibly traps spores in an alternative, time-delayed, and low yield germination pathway. Our results are also consistent with kinetic data suggesting the existence of at least two distinct bile salt binding sites in C. difficile spores.

Biomechanics of the tether breakage: tensile behaviour of a single-unit vertebral body tethering construct.

PURPOSE: Tether breakage was reported as the most common complication of vertebral body tethering. However, as the literature suggests the physiological loads do not have the potential to cause the failure of the tether. Currently, the biomechanical reason behind the tether breakage is unknown. The current study aims to elucidate the effects of the tension forces on the failure mechanisms of the VBT and provide mechanical justification for how it can be identified radiographically. METHODS: Tensile tests (20%/min strain rate) were performed on single-unit VBT samples. Failure modes and mechanical characteristics were reported. RESULTS: The failure took place prematurely due to the slippage of the tether at the screw-tether junction where the tether is damaged significantly by the locking cap. Slippage was initiated at 10-13% tensile strain level where the tensile stress and tension force were 50.4 ± 1.5 MPa and 582.2 ± 30.8 N, respectively. CONCLUSION: The failure occurs because of high-stress concentrations generated within the locking region which damages the tether surface and leads to the slippage of the tether. We observed that the loads leading to failure are within the physiological limits and may indicate the high likelihood of the tether breakage. The failure mode observed in our study is shown to be the dominant failure mode, and a design improvement on the gripping mechanism is suggested to avoid failure at the screw-tether junction. We observed that the tether elongates 10-13% prior to the breakage, which can be employed as a diagnostic criterion to screen for tether breakages radiographically.

Antifouling Properties of Pluronic and Tetronic Surfactants in Digital Microfluidics.

Fouling at liquid-solid interfaces is a pernicious problem for a wide range of applications, including those that are implemented by digital microfluidics (DMF). There are several strategies that have been used to combat surface fouling in DMF, the most common being inclusion of amphiphilic surfactant additives in the droplets to be manipulated. Initial studies relied on Pluronic additives, and more recently, Tetronic additives have been used, which has allowed manipulation of complex samples like serum and whole blood. Here, we report our evaluation of 19 different Pluronic and Tetronic additives, with attempts to determine (1) the difference in antifouling performance between the two families, (2) the structural similarities that predict exceptional antifouling performance, and (3) the mechanism of the antifouling behavior. Our analysis shows that both Pluronic and Tetronic additives with modest molar mass, poly(propylene oxide) (PPO) ≥50 units, poly(ethylene oxide) (PEO) mass percentage ≤50%, and hydrophilic-lipophilic balance (HLB) ca. 13-15 allow for exceptional antifouling performance in DMF. The most promising candidates, P104, P105, and T904, were able to support continuous movement of droplets of serum for more than 2 h, a result (for devices operating in air) previously thought to be out of reach for this technique. Additional results generated using device longevity assays, intrinsic fluorescence measurements, dynamic light scattering, asymmetric flow field flow fractionation, supercritical angle fluorescence microscopy, atomic force microscopy, and quartz crystal microbalance measurements suggest that the best-performing surfactants are more likely to operate by forming a protective layer at the liquid-solid interface than by complexation with proteins. We propose that these results and their implications are an important step forward for the growing community of users of this technique, which may provide guidance in selecting surfactants for manipulating biological matrices for a wide range of applications.

Monitoring non-specific adsorption at solid-liquid interfaces by supercritical angle fluorescence microscopy.

Supercritical angle fluorescence (SAF) microscopy is a novel imaging tool based on the use of distance-dependent fluorophore emission patterns to provide accurate locations of fluorophores relative to a surface. This technique has been extensively used to construct accurate cellular images and to detect surface phenomena in a static environment. However, the capability of SAF microscopy in monitoring dynamic surface phenomena and changes in millisecond intervals is underexplored in the literature. Here, we report on a hardware add-on for a conventional inverted microscope coupled with a post-processing Python module that extends the capability of SAF microscopy to monitor dynamic surface adsorption in sub-second intervals, thereby greatly expanding the potential of this tool to study surface interactions, such as surface fouling and competitive surface adhesion. The Python module enables researchers to automatically extract SAF profiles from each image. We first assessed the performance of the system by probing the specific binding of biotin-fluorescein conjugates to a neutravidin-coated cover glass in the presence of non-binding fluorescein. The SAF emission was observed to increase with the quantity of bound fluorophore on the cover glass. However, a high concentration of unbound fluorophore also contributed to overall SAF emission, leading to over-estimation in surface-bound fluorescence. To expand the applications of SAF in monitoring surface phenomena, we monitored the non-specific surface adsorption of BSA and non-ionic surfactants on a Teflon-AF surface. Solution mixtures of bovine serum albumin (BSA) and nine Pluronic/Tetronic surfactants were exposed to a Teflon-AF surface. No significant BSA adsorption was observed in all BSA-surfactant solution mixtures with negligible SAF intensity. Finally, we monitored the adsorption dynamics of BSA onto the Teflon-AF surface and observed rapid BSA adsorption on Teflon-AF surface within 10 s of addition. The adsorption rate constant (ka) and half-life of BSA adsorption on Teflon-AF were determined to be 0.419 ± 0.004 s-1 and 1.65 ± 0.016 s, respectively, using a pseudo-first-order adsorption equation.

Targeting Apollo-NADP+ to Image NADPH Generation in Pancreatic Beta-Cell Organelles.

NADPH/NADP+ redox state supports numerous reactions related to cell growth and survival; yet the full impact is difficult to appreciate due to organelle compartmentalization of NADPH and NADP+. To study glucose-stimulated NADPH production in pancreatic beta-cell organelles, we targeted the Apollo-NADP+ sensor by first selecting the most pH-stable version of the single-color sensor. We subsequently targeted mTurquoise2-Apollo-NADP+ to various organelles and confirmed activity in the cytoplasm, mitochondrial matrix, nucleus, and peroxisome. Finally, we measured the glucose- and glutamine-stimulated NADPH responses by single- and dual-color imaging of the targeted sensors. Overall, we developed multiple organelle-targeted Apollo-NADP+ sensors to reveal the prominent role of beta-cell mitochondria in determining NADPH production in the cytoplasm, nucleus, and peroxisome.

Tmem65 is critical for the structure and function of the intercalated discs in mouse hearts.

The intercalated disc (ICD) is a unique membrane structure that is indispensable to normal heart function, yet its structural organization is not completely understood. Previously, we showed that the ICD-bound transmembrane protein 65 (Tmem65) was required for connexin43 (Cx43) localization and function in cultured mouse neonatal cardiomyocytes. Here, we investigate the functional and cellular effects of Tmem65 reductions on the myocardium in a mouse model by injecting CD1 mouse pups (3-7 days after birth) with recombinant adeno-associated virus 9 (rAAV9) harboring Tmem65 shRNA, which reduces Tmem65 expression by 90% in mouse ventricles compared to scrambled shRNA injection. Tmem65 knockdown (KD) results in increased mortality which is accompanied by eccentric hypertrophic cardiomyopathy within 3 weeks of injection and progression to dilated cardiomyopathy with severe cardiac fibrosis by 7 weeks post-injection. Tmem65 KD hearts display depressed hemodynamics as measured echocardiographically as well as slowed conduction in optical recording accompanied by prolonged PR intervals and QRS duration in electrocardiograms. Immunoprecipitation and super-resolution microscopy demonstrate a physical interaction between Tmem65 and sodium channel ß subunit (ß1) in mouse hearts and this interaction appears to be required for both the establishment of perinexal nanodomain structure and the localization of both voltage-gated sodium channel 1.5 (NaV1.5) and Cx43 to ICDs. Despite the loss of NaV1.5 at ICDs, whole-cell patch clamp electrophysiology did not reveal reductions in Na+ currents but did show reduced Ca2+ and K+ currents in Tmem65 KD cardiomyocytes in comparison to control cells. We conclude that disrupting Tmem65 function results in impaired ICD structure, abnormal cardiac electrophysiology, and ultimately cardiomyopathy.

Correlated STORM-homoFRET imaging reveals highly heterogeneous membrane receptor structures.

Mapping the self-organization and spatial distribution of membrane proteins is key to understanding their function. Developing methods that can provide insight into correlations between membrane protein colocalization and interactions is challenging. We report here on a correlated stochastic optical reconstruction microscopy/homoFRET imaging approach for resolving the nanoscale distribution and oligomeric state of membrane proteins. Using live cell homoFRET imaging of carcinoembryonic antigen-related cellular adhesion molecule 1, a cell-surface receptor known to exist in a complex equilibrium between monomer and dimer/oligomer states, we revealed highly heterogeneous diffraction-limited structures on the surface of HeLa cells. Furthermore, correlated super-resolved stochastic optical reconstruction microscopy imaging showed that these structures comprised a complex mixture and spatial distribution of self-associated carcinoembryonic antigen-related cellular adhesion molecule 1 molecules. In conclusion, this correlated approach provides a compelling strategy for addressing challenging questions about the interplay between membrane protein concentration, distribution, interaction, clustering, and function.

Egg-laying and locomotory screens with C. elegans yield a nematode-selective small molecule stimulator of neurotransmitter release.

Nematode parasites of humans, livestock and crops dramatically impact human health and welfare. Alarmingly, parasitic nematodes of animals have rapidly evolved resistance to anthelmintic drugs, and traditional nematicides that protect crops are facing increasing restrictions because of poor phylogenetic selectivity. Here, we exploit multiple motor outputs of the model nematode C. elegans towards nematicide discovery. This work yielded multiple compounds that selectively kill and/or immobilize diverse nematode parasites. We focus on one compound that induces violent convulsions and paralysis that we call nementin. We find that nementin stimulates neuronal dense core vesicle release, which in turn enhances cholinergic signaling. Consequently, nementin synergistically enhances the potency of widely-used non-selective acetylcholinesterase (AChE) inhibitors, but in a nematode-selective manner. Nementin therefore has the potential to reduce the environmental impact of toxic AChE inhibitors that are used to control nematode infections and infestations.

Functional recovery priorities and community rehabilitation service preferences of spinal cord injury individuals and caregivers of Chinese ethnicity and cultural background.

Introduction: Spinal cord injury (SCI) causes significant and permanent disability affecting motor, sensory and autonomic functions. We conducted a survey on the priorities of functional recovery and preferences for community rehabilitation services in a cohort of Chinese individuals with SCI as well as the primary caregivers. The study also investigated their views on advanced technology and research. Methods: An online platform with a self-administered questionnaire was used to collect the opinions of clients that received services from an SCI follow-up clinic, a self-help association, or a non-government organization from 1 September-31 December 2021. Results: Eighty-seven subjects (74 individuals with SCI-48 tetraplegic, 26 paraplegic, and 13 caregivers) responded to the survey. Recovery of arm/hand function was given the highest priority among tetraplegics, followed by upper trunk/body strength and balance, and bladder/bowel function. Sexual function had a significant lower ranking than all priority areas except normal sensation (p < 0.05). Paraplegics viewed bladder/bowel function as the most important area of functional recovery, followed by walking movement, upper trunk/body strength and balance, elimination of chronic pain, and regaining normal sensation. There was no statistically significant difference among the top priority areas (p > 0.05). In contrast to previous studies done in Western populations, the study revealed that sexual function was ranked as the lowest by all 3 groups of respondents (tetraplegics, paraplegics, and caregivers). The majority of participants thought community rehabilitation services were inadequate. Most of the respondents were interested to try advanced technology which would facilitate their daily life and rehabilitation. About half of the individuals with SCI thought advance in technology and research could bring significant improvement in their quality of life in the coming 10 years. Conclusion: This survey is the first study specifically looking into the recovery and rehabilitation priorities of a Chinese population of individuals with SCI. This is also the first study to investigate the priorities of the primary caregivers of SCI individuals. The findings are useful as a reference for planning of future research and provision of rehabilitation services for the SCI community locally and in other parts of China.

Design of a versatile microfluidic device for imaging precision-cut-tissue slices.

Precision-cut-tissues (PCTs), which preserve many aspects of a tissue's microenvironment, are typically imaged using conventional sample dishes and chambers. These can require large amounts of reagent and, when used for flow-through experiments, the shear forces applied on the tissues are often ill-defined. Their physical design also makes it difficult to image large volumes and repetitively image smaller regions of interest in the living slice. We report here on the design of a versatile microfluidic device capable of holding mouse or human pancreas PCTs for 3D fluorescence imaging using confocal and selective plane illumination microscopy (SPIM). Our design positions PCTs within a 5 × 5 mm × 140µm deep chamber fitted with 150µm tall channels to facilitate media exchange. Shear stress in the device is localized to small regions on the surface of the tissue and can be easily controlled. This design allows for media exchange at flowrates ∼10-fold lower than those required for conventional chambers. Finally, this design allows for imaging the same immunofluorescently labeled PCT with high resolution on a confocal and with large field of view on a SPIM, without adversely affecting image quality.

Evaluating the attitudes and behavior of Hong Kong medical students toward receiving the COVID-19 vaccine.

Getting vaccinated against SARS-CoV-2 lowers the risk of severe infections. In Hong Kong, two vaccine types are offered: CoronaVac by Sinovac Biotech (Sinovac), and Comirnaty by BioNTech-Fosun Pharma (BioNTech). However, a low vaccine uptake rate is observed. This study primarily aimed to determine the population of medical students who underwent COVID-19 vaccination, and to identify factors associated with their decision on timing and vaccine type. Current medical students from The University of Hong Kong (HKU) were invited to participate in this cross-sectional survey study from 16 September to 31 December 2021. The main outcome measures were the vaccine uptake rate, primary reasons for vaccine-seeking behavior, vaccine hesitancy and vaccine preference, as well as information sources. All questions were of a multiple-choice format, with a free response option for questions pertaining to reason exploration. Overall, 214 medical students participated in the study, with all questionnaires analyzed. Amongst the 98.1% that completed 2 doses, 93.4% selected BioNTech and 6.6% selected Sinovac. Significant associations were observed between year groups and vaccine timing (p = 0.00989). The primary reason to seek vaccination was immunity against COVID-19 (53.5%), while the fear of potential side effects (61.6%) accounted for vaccine hesitancy. The BioNTech vaccine was favored for its higher efficacy against COVID-19 (87.4%). Information sources were mainly from HKU professors (64.6%) and social media (59.9%). The study found a high vaccine uptake rate amongst medical students, contrary to the situation observed in the Hong Kong general population at the time of the study.

This is the first paper evaluating the attitudes and behaviours of Hong Kong medical students towards the COVID-19 vaccine.High COVID-19 vaccine uptake observed amongst HKU medical students, with a predilection towards Comirnaty by BioNTech-Fosun Pharma for the first and second dose.Clinical medical students are more likely to get their COVID-19 vaccine earlier than preclinical medical students.Immunity against COVID-19 was the most compelling reason for students to get vaccinated, whilst fears over side effects was the main reason for vaccine hesitancy.

Patellar Microfracture: Internal Stabilization House-on-Stilts Technique to Achieve Better Results.

Microfractures are the common first choice for the treatment of osteochondral lesions, because of their high efficacy and low cost and operating time compared with other surgical techniques. Results of microfractures for retropatellar chondral defects are subpar compared with other compartments of the knee, despite the patellofemoral compartment being the second most common compartment for such lesions. One major reason for the inferiority is the mobility of the patella, which is most prominent when the patient's knee is extended, as is the case in this type of surgery. Traditionally, this obstacle was dealt with by applying manual pressure, which is unreliable and prone to technical difficulties, such as skiving of the awl and a narrowed operating view, as well as complications such as fractures. This Technical Note introduces a new technique, which we have named "house-on-stilts," that uses multiple Kirschner wire fixations through the patella and femur to immobilize the patella and is essentially an internal stabilization. This technique aids not only the microfracturing process but also the preceding debridement stage, at no increased cost or operating time.

Knowledge Gaps in Biophysical Changes After Powered Robotic Exoskeleton Walking by Individuals With Spinal Cord Injury-A Scoping Review.

In addition to helping individuals with spinal cord injury (SCI) regain the ability to ambulate, the rapidly evolving capabilities of robotic exoskeletons provide an array of secondary biophysical benefits which can reduce the complications resulting from prolonged immobilization. The proposed benefits of increased life-long over-ground walking capacity include improved upper body muscular fitness, improved circulatory response, improved bowel movement regularity, and reduced pain and spasticity. Beyond the positive changes related to physical and biological function, exoskeletons have been suggested to improve SCI individuals' quality of life (QOL) by allowing increased participation in day-to-day activities. Most of the currently available studies that have reported on the impact of exoskeletons on the QOL and prevention of secondary health complications on individuals with SCI, are of small scale and are heterogeneous in nature. Moreover, few meta-analyses and reviews have attempted to consolidate the dispersed data to reach more definitive conclusions of the effects of exoskeleton use. This scoping review seeks to provide an overview on the known effects of overground exoskeleton use, on the prevention of secondary health complications, changes to the QOL, and their effect on the independence of SCI individuals in the community settings. Moreover, the intent of the review is to identify gaps in the literature currently available, and to make recommendations on focus study areas and methods for future investigations.