Clinical Outcomes of "Paralyzed" Nerve Transfer for Treating Spinal Cord Injury: A Proof of Concept in a Human Model.

Functional electrical stimulation (FES) is an option to restore function in individuals after high cervical spinal cord injury (SCI) who have limited available options for tendon or nerve transfer. To be considered for FES implantation, patients must possess upper motor neuron (UMN) type denervation in potential recipient muscles, which can be confirmed by response to surface electrical stimulation during clinical evaluation. Lower motor neuron (LMN) denervated muscles will not respond to electrical stimulation and, therefore, are unavailable for use in an FES system. Previous animal studies have demonstrated that a "paralyzed" nerve transfer of a UMN-denervated motor branch to an LMN-denervated motor branch can restore electrical excitability in the recipient. In this study, we report the indications, surgical technique, and successful outcome (restoration of M3 elbow flexion) after the first "paralyzed" nerve transfer in a human patient.

Designing policy for Earth's urban future.

Global impacts of cities must be better conveyed to multilateral organizations.

Ticagrelor inverse agonist activity at the P2Y12 receptor is non-reversible versus its endogenous agonist adenosine 5´-diphosphate.

BACKGROUND AND PURPOSE: Ticagrelor is labelled as a reversible, direct-acting platelet P2Y12 receptor (P2Y12 R) antagonist that is indicated clinically for the prevention of thrombotic events in patients with acute coronary syndrome (ACS). As with many antiplatelet drugs, ticagrelor therapy increases bleeding risk in patients, which may require platelet transfusion in emergency situations. The aim of this study was to further examine the reversibility of ticagrelor at the P2Y12 R. EXPERIMENTAL APPROACH: Studies were performed in human platelets, with P2Y12 R-stimulated GTPase activity and platelet aggregation assessed. Cell-based bioluminescence resonance energy transfer (BRET) assays were undertaken to assess G protein-subunit activation downstream of P2Y12 R activation. KEY RESULTS: Initial studies revealed that a range of P2Y12 R ligands, including ticagrelor, displayed inverse agonist activity at P2Y12 R. Only ticagrelor was resistant to washout and, in human platelet and cell-based assays, washing failed to reverse ticagrelor-dependent inhibition of ADP-stimulated P2Y12 R function. The P2Y12 R agonist 2MeSADP, which was also resistant to washout, was able to effectively compete with ticagrelor. In silico docking revealed that ticagrelor and 2MeSADP penetrated more deeply into the orthosteric binding pocket of the P2Y12 R than other P2Y12 R ligands. CONCLUSION AND IMPLICATIONS: Ticagrelor binding to P2Y12 R is prolonged and more akin to that of an irreversible antagonist, especially versus the endogenous P2Y12 R agonist ADP. This study highlights the potential clinical need for novel ticagrelor reversal strategies in patients with spontaneous major bleeding, and for bleeding associated with urgent invasive procedures.

Preoperative evaluation of nerve transfer recipients after spinal cord injury using stimulated manual muscle testing.

Nerve transfer after spinal cord injury has become increasingly popular. Accurate preoperative identification of lower motor neuron involvement in potential recipient nerves is critical. Electrodiagnostic testing has been shown to correlate with intraoperative findings; however, it is time-consuming, costly and may not be readily available. Stimulated manual muscle testing is an alternative diagnostic approach. It is inexpensive and easily done by the surgeon or therapist in the office; however, correlation with intraoperative stimulation has not been reported. A retrospective review was conducted for patients who underwent nerve transfer for tetraplegia with recorded preoperative stimulated manual muscle testing and intraoperative stimulation results. Nine patients including 37 nerve transfers were included. Of the 37 nerve transfers, 36 were accurately graded preoperatively by stimulated manual muscle testing. Stimulated manual muscle testing had a sensitivity of 89%, specificity of 100%, positive predictive value of 100% and a negative predictive value of 97%. This study supports stimulated manual muscle testing for preoperative distinction between upper versus lower motor neuron injuries.Level of evidence: IV.

How do density, employment and transit affect the prevalence of COVID-19 pandemic? A study of 3,141 counties across the United States.

Previous research has explored the effect of the built environment on the spread of the coronavirus disease (COVID-19) pandemic. This study extends the existing literature by examining the relationship between pandemic prevalence and density, employment, and transit factors at the county level. Using multilinear spatial-lag regressions and time series clustering analyses on the Smart Location Database encompassing 3141 counties in the United States, our findings reveal the following: (1) Density, employment, and transit variables yield heterogeneous effects to infection rate, death rate, and mortality rate. (2) Pedestrian-oriented road density is positively correlated to the prevalence of COVID-19, every 0.011 miles/acre increase is associated with 1% increase in the infection rate. (3) A consistent negative correlation is observed between jobs per household and infection rate, while a decrease in unemployment rate leads to an increase in the death rate. (4) The results from time series analysis suggest that areas characterized by low auto-oriented intersection density but high pedestrian-oriented road density are more susceptible to the impacts of pandemics. This highlights the need to prioritize pandemic prevention efforts in the suburban and rural areas with low population density, as emphasized in existing literature emphasized.

Improving hand function after spinal cord injury.

Nerve transfer surgery has expanded reconstructive options for restoring upper extremity function following spinal cord injury. By adding new motor donors to the pool already available through tendon transfers, the effectiveness of treatment should improve. Planning which procedures and in which order to perform, along with their details must be delineated. To meet these demands, refined diagnostics are needed, along with awareness of the remaining challenges to restore intrinsic muscle function and to address spasticity and its consequences. This article summaries recent advances in surgical reanimation of upper extremity motor control, together with an overview of the development of neuro-prosthetic and neuromodulation techniques to modify recovery or substitute for functional losses after spinal cord injuries.

A qualitative investigation into the perceived therapeutic benefits and barriers of a surf therapy intervention for youth mental health.

OBJECTIVE: This study aims to investigate potential therapeutic pathways and barriers to participation in a surf therapy program for youth at risk of mental health problems from the perspective of participants, surf mentors and program coordinator. METHOD: Nineteen individuals, consisting of youth (n = 9, 5 male, 4 female, M = 12.8, SD = 2.6), mentors (n = 9, male 5, female 4, M = 37.60, SD = 13.62) and the Ocean Mind program coordinator (n = 1, male, age 26 years), participated in semi-structured focus groups or follow-up interviews. This qualitative study analysed data using inductive thematic analysis. RESULTS: Six themes were identified in total, with self-efficacy, interpersonal skills and forming a mentorship being potential therapeutic pathways of the surf therapy intervention. Surf instruction techniques and family engagement were both identified as potential barriers that negatively affect participant engagement. Additionally, the natural environment was identified as both a potential therapeutic pathway and a barrier. CONCLUSION: Surf therapy interventions appears to hold a number of benefits for youth mental health via pathways relating to the promotion of mental health protective factors.

Comparing tweet sentiments in megacities using machine learning techniques: In the midst of COVID-19.

COVID-19 was announced by the World Health Organization as a pandemic on March 11, 2020. Not only has COVID-19 struck the economy and public health, but it also has deep influences on people's feelings. Twitter, as an active social media, is a great database where we can investigate people's sentiments during this pandemic. By conducting sentiment analysis on Tweets using advanced machine learning techniques, this study aims to investigate how public sentiments respond to the pandemic from March 2 to May 21, 2020 in New York City, Los Angeles, London, and another six global mega-cities. Results showed that across cities, negative and positive Tweet sentiment clustered around mid-March and early May, respectively. Furthermore, positive sentiments of Tweets from New York City and London were positively correlated with stricter quarantine measures, although this correlation was not significant in Los Angeles. Meanwhile, Tweet sentiments of all three cities did not exhibit a strong correlation with new cases and hospitalization. Last but not least, we provide a qualitative analysis of the reasons behind differences in correlations shown above, along with a discussion of the polarizing effect of public policies on Tweet sentiments. Thus, the results of this study imply that Tweet sentiment is more sensitive to quarantine orders than reported statistics of COVID-19, especially in populous megacities where public transportation is heavily relied upon, which calls for prompt and effective quarantine measures during contagious disease outbreaks.

The south american context of diagnostic disclosure of adolescents infected by HIV/AIDS: a systematic literature review.

OBJECTIVE: To analyze the scientific evidence on the disclosure of the diagnostic of adolescents infected by HIV/AIDS in the South American context. DATABASE: Systematic literature review using the PubMed, Cinahal, Embase, Cochrane, BVS, and Global Health databases and the descriptors: adolescent and HIV and family and Argentina or Bolivia or Brasil or Chile or Colombia or Ecuador or French Guiana or Paraguay or Peru or Uruguay or Venezuela. DATA SYNTHESIS: Brasil was the country highlighted. It was verified that parents have a direct and indirect influence over the adolescents' life, especially regarding behaviors and health care. Dialog among family members can reduce adolescents' vulnerability to HIV and encourage diagnostic disclosure. CONCLUSION: It is necessary to amplify research involving adolescents with HIV/AIDS and their parents/caregivers and family members to improve care and reduce the cases of the disease. It is suggested that policies of prevention and treatment should involve families, caregivers, partners, and the community.

The south american context of diagnostic disclosure of adolescents infected by HIV/AIDS: a systematic literature review

SUMMARY OBJECTIVE To analyze the scientific evidence on the disclosure of the diagnostic of adolescents infected by HIV/AIDS in the South American context. DATABASE Systematic literature review using the PubMed, Cinahal, Embase, Cochrane, BVS, and Global Health databases and the descriptors: adolescent and HIV and family and Argentina or Bolivia or Brasil or Chile or Colombia or Ecuador or French Guiana or Paraguay or Peru or Uruguay or Venezuela. DATA SYNTHESIS Brasil was the country highlighted. It was verified that parents have a direct and indirect influence over the adolescents' life, especially regarding behaviors and health care. Dialog among family members can reduce adolescents' vulnerability to HIV and encourage diagnostic disclosure. CONCLUSION It is necessary to amplify research involving adolescents with HIV/AIDS and their parents/caregivers and family members to improve care and reduce the cases of the disease. It is suggested that policies of prevention and treatment should involve families, caregivers, partners, and the community.

RESUMO OBJETIVO Analisar as evidências científicas acerca da revelação diagnóstica de adolescentes infectados pelo HIV/aids no contexto sul-americano. FONTES DE DADOS Revisão sistemática da literatura nas bases de dados PubMed, Cinahal, Embase, Cochrane, BVS e Global Health, utilizando os descritores adolescent and HIV and family and Argentina or Bolivia or Brasil or Chile or Colombia or Equador or French Guiana or Paraguay or Peru or Uruguay or Venezuela. SÍNTESE DOS DADOS O Brasil foi o país de destaque. Verificou-se que os pais exercem influência direta e indireta sobre a vida dos adolescentes, especialmente com relação aos comportamentos e cuidados de saúde. O diálogo entre os membros da família pode reduzir a vulnerabilidade dos adolescentes ao HIV e encorajar a revelação do diagnóstico. CONCLUSÃO É necessário ampliar a pesquisa envolvendo adolescentes, pais/cuidadores, famílias com HIV/aids para melhorar os cuidados e reduzir os casos da doença. Sugere-se que as políticas de prevenção e tratamento envolvam famílias, cuidadores, parceiros e comunidades.

A Rare Case of Cervical Charcot After Spinal Cord Injury: A Case Report.

CASE: We present a rare case of cervical Charcot disease that was diagnosed in a paraplegic patient by loss of function caudal to the original level of spinal cord injury. Clinical imaging, diagnosis, differentials, and operative management are discussed. CONCLUSIONS: Charcot disease of the cervical spine is rare and very difficult to diagnose in the paraplegic patient population. High clinical suspicion should be maintained in these patients who demonstrate any form of neurologic deterioration, mechanical instability, or change in spinal alignment. It is often necessary to rule out infection. Spinal decompression and surgical stabilization is the treatment of choice.

Distribution of preoperative and postoperative astigmatism in a large population of patients undergoing cataract surgery in the UK.

PURPOSE: To assess the prevalence and severity of preoperative and postoperative astigmatism in patients with cataract in the UK. SETTING: Data from 8 UK National Health Service ophthalmology clinics using MediSoft electronic medical records (EMRs). DESIGN: Retrospective cohort study. METHODS: Eyes from patients aged ≥65 years undergoing cataract surgery were analysed. For all eyes, preoperative (corneal) astigmatism was evaluated using the most recent keratometry measure within 2 years prior to surgery. For eyes receiving standard monofocal intraocular lens (IOLs), postoperative refractive astigmatism was evaluated using the most recent refraction measure within 2-12 months postsurgery. A power vector analysis compared changes in the astigmatic 2-dimensional vector (J0, J45) before and after surgery, for the subgroup of eyes with both preoperative and postoperative astigmatism measurements. Visual acuity was also assessed preoperatively and postoperatively. RESULTS: Eligible eyes included in the analysis were 110 468. Of these, 78% (n=85 650) had preoperative (corneal) astigmatism ≥0.5 dioptres (D), 42% (n=46 003) ≥1.0 D, 21% (n=22 899) ≥1.5 D and 11% (n=11 651) ≥2.0 D. After surgery, the refraction cylinder was available for 39 744 (36%) eyes receiving standard monofocal IOLs, of which 90% (n=35 907) had postoperative astigmatism ≥0.5 D and 58% (n=22 886) ≥1.0 D. Visual acuity tended to worsen postoperatively with increased astigmatism (ρ=-0.44, P<0.01). CONCLUSIONS: There is a significant burden of preoperative astigmatism in the UK cataract population. The available refraction data indicate that this burden is not reduced after surgery with implantation of standard monofocal IOLs. Measures should be taken to improve visual outcomes of patients with astigmatic cataract by simultaneously correcting astigmatism during cataract surgery.

Evolution of Neuroprosthetic Approaches to Restoration of Upper Extremity Function in Spinal Cord Injury.

Background: Spinal cord injury (SCI) occurring at the cervical levels can result in significantly impaired arm and hand function. People with cervical-level SCI desire improved use of their arms and hands, anticipating that regained function will result in improved independence and ultimately improved quality of life. Neuroprostheses provide the most promising method for significant gain in hand and arm function for persons with cervical-level SCI. Neuroprostheses utilize small electrical currents to activate peripheral motor nerves, resulting in controlled contraction of paralyzed muscles. Methods: A myoelectrically-controlled neuroprosthesis was evaluated in 15 arms in 13 individuals with cervical-level SCI. All individuals had motor level C5 or C6 tetraplegia. Results: This study demonstrates that an implanted neuroprosthesis utilizing myoelectric signal (MES)-controlled stimulation allows considerable flexibility in the control algorithms that can be utilized for a variety of arm and hand functions. Improved active range of motion, grip strength, and the ability to pick up and release objects were improved in all arms tested. Adverse events were few and were consistent with the experience with similar active implantable devices. Conclusion: For individuals with cervical SCI who are highly motivated, implanted neuroprostheses provide the opportunity to gain arm and hand function that cannot be gained through the use of orthotics or surgical intervention alone. Upper extremity neuroprostheses have been shown to provide increased function and independence for persons with cervical-level SCI.

Global prevalence and economic and humanistic burden of astigmatism in cataract patients: a systematic literature review.

PURPOSE: To systematically review the published evidence on the prevalence and economic and humanistic burden of astigmatism in cataract patients. MATERIALS AND METHODS: For this systematic literature review, the Medline, PubMed, Embase, and Cochrane databases were searched from 1996 to September 2015 for available scientific literature that met the inclusion criteria. Studies published in the English language reporting prevalence and humanistic and economic burden in patients diagnosed with cataract and astigmatism were included. RESULTS: Of 3,649 papers reviewed, 31 studies from 32 publications met the inclusion criteria of this review. Preexisting astigmatism ≥1 D was present in up to 47% of cataract eyes. The cost burden of residual uncorrected astigmatism after cataract surgery was driven by the cost of spectacles, which was estimated to range from $2,151 to $3,440 in the US and $1,786 to $4,629 in Europe over a lifetime. In cataract patients, both preexisting and postoperative residual astigmatism were associated with poor vision-related patient satisfaction and quality of life, as well as higher spectacle burden. Astigmatism correction during cataract surgery appears to improve visual outcomes and results in overall lifetime cost savings compared to astigmatism correction with postoperative vision correction. CONCLUSION: There is a high prevalence of preexisting astigmatism in cataract patients. Although published data are limited, both preoperative astigmatism and postoperative residual astigmatism affect visual function and vision-related quality of life, resulting in increased humanistic burden. Suboptimal correction of astigmatism during cataract surgery drives the continuous need for vision correction with spectacles in the postoperative period. Patients must bear the out-of-pocket expenses, since payers often do not reimburse the cost of spectacles. Greater access to astigmatism correction during cataract surgery could improve visual outcomes and quality of life in patients. More research is required to gain a better understanding of the disease burden of astigmatism in cataract patients.

Novel use of rituximab in macrophage activation syndrome secondary to systemic lupus erythematosus.

Macrophage activation syndrome (MAS) is a rare disease characterised by aberrant immune hyperactivation of T lymphocytes and macrophages driven by cytokine dysfunction. The HLH-2004 protocol is commonly used for the treatment of MAS, but significant toxicities are associated. We describe a case of MAS secondary to systemic lupus erythematosus in a young female that responded well to rituximab in lieu of etoposide. She continues to be in remission 1 year following the completion of rituximab infusion and is maintained on hydroxychloroquine. This case highlights the need for further research on the use of rituximab and other available biologics in the setting of MAS in order to help guide further alternative treatment decisions.

Restoration of reaching and grasping movements through brain-controlled muscle stimulation in a person with tetraplegia: a proof-of-concept demonstration.

BACKGROUND: People with chronic tetraplegia, due to high-cervical spinal cord injury, can regain limb movements through coordinated electrical stimulation of peripheral muscles and nerves, known as functional electrical stimulation (FES). Users typically command FES systems through other preserved, but unrelated and limited in number, volitional movements (eg, facial muscle activity, head movements, shoulder shrugs). We report the findings of an individual with traumatic high-cervical spinal cord injury who coordinated reaching and grasping movements using his own paralysed arm and hand, reanimated through implanted FES, and commanded using his own cortical signals through an intracortical brain-computer interface (iBCI). METHODS: We recruited a participant into the BrainGate2 clinical trial, an ongoing study that obtains safety information regarding an intracortical neural interface device, and investigates the feasibility of people with tetraplegia controlling assistive devices using their cortical signals. Surgical procedures were performed at University Hospitals Cleveland Medical Center (Cleveland, OH, USA). Study procedures and data analyses were performed at Case Western Reserve University (Cleveland, OH, USA) and the US Department of Veterans Affairs, Louis Stokes Cleveland Veterans Affairs Medical Center (Cleveland, OH, USA). The study participant was a 53-year-old man with a spinal cord injury (cervical level 4, American Spinal Injury Association Impairment Scale category A). He received two intracortical microelectrode arrays in the hand area of his motor cortex, and 4 months and 9 months later received a total of 36 implanted percutaneous electrodes in his right upper and lower arm to electrically stimulate his hand, elbow, and shoulder muscles. The participant used a motorised mobile arm support for gravitational assistance and to provide humeral abduction and adduction under cortical control. We assessed the participant's ability to cortically command his paralysed arm to perform simple single-joint arm and hand movements and functionally meaningful multi-joint movements. We compared iBCI control of his paralysed arm with that of a virtual three-dimensional arm. This study is registered with ClinicalTrials.gov, number NCT00912041. FINDINGS: The intracortical implant occurred on Dec 1, 2014, and we are continuing to study the participant. The last session included in this report was Nov 7, 2016. The point-to-point target acquisition sessions began on Oct 8, 2015 (311 days after implant). The participant successfully cortically commanded single-joint and coordinated multi-joint arm movements for point-to-point target acquisitions (80-100% accuracy), using first a virtual arm and second his own arm animated by FES. Using his paralysed arm, the participant volitionally performed self-paced reaches to drink a mug of coffee (successfully completing 11 of 12 attempts within a single session 463 days after implant) and feed himself (717 days after implant). INTERPRETATION: To our knowledge, this is the first report of a combined implanted FES+iBCI neuroprosthesis for restoring both reaching and grasping movements to people with chronic tetraplegia due to spinal cord injury, and represents a major advance, with a clear translational path, for clinically viable neuroprostheses for restoration of reaching and grasping after paralysis. FUNDING: National Institutes of Health, Department of Veterans Affairs.

Voluntary activation of biceps-to-triceps and deltoid-to-triceps transfers in quadriplegia.

The biceps or the posterior deltoid can be transferred to improve elbow extension function for many individuals with C5 or C6 quadriplegia. Maximum strength after elbow reconstruction is variable; the patient's ability to voluntarily activate the transferred muscle to extend the elbow may contribute to the variability. We compared voluntary activation during maximum isometric elbow extension following biceps transfer (n = 5) and deltoid transfer (n = 6) in three functional postures. Voluntary activation was computed as the elbow extension moment generated during maximum voluntary effort divided by the moment generated with full activation, which was estimated via electrical stimulation. Voluntary activation was on average 96% after biceps transfer and not affected by posture. Individuals with deltoid transfer demonstrated deficits in voluntary activation, which differed by posture (80% in horizontal plane, 69% in overhead reach, and 70% in weight-relief), suggesting inadequate motor re-education after deltoid transfer. Overall, individuals with a biceps transfer better activated their transferred muscle than those with a deltoid transfer. This difference in neural control augmented the greater force-generating capacity of the biceps leading to increased elbow extension strength after biceps transfer (average 9.37 N-m across postures) relative to deltoid transfer (average 2.76 N-m across postures) in our study cohort.

Posture-Dependent Corticomotor Excitability Differs Between the Transferred Biceps in Individuals With Tetraplegia and the Biceps of Nonimpaired Individuals.

BACKGROUND: Following biceps transfer to enable elbow extension in individuals with tetraplegia, motor re-education may be facilitated by greater corticomotor excitability. Arm posture modulates corticomotor excitability of the nonimpaired biceps. If arm posture also modulates excitability of the transferred biceps, posture may aid in motor re-education. OBJECTIVE: Our objective was to determine whether multi-joint arm posture affects corticomotor excitability of the transferred biceps similar to the nonimpaired biceps. We also aimed to determine whether corticomotor excitability of the transferred biceps is related to elbow extension strength and muscle length. METHODS: Corticomotor excitability was assessed in 7 arms of individuals with tetraplegia and biceps transfer using transcranial magnetic stimulation and compared to biceps excitability of nonimpaired individuals. Single-pulse transcranial magnetic stimulation was delivered to the motor cortex with the arm in functional postures at rest. Motor-evoked potential amplitude was recorded via surface electromyography. Elbow moment was recorded during maximum isometric extension trials, and muscle length was estimated using a biomechanical model. RESULTS: Arm posture modulated corticomotor excitability of the transferred biceps differently than the nonimpaired biceps. Elbow extension strength was positively related and muscle length was unrelated, respectively, to motor-evoked potential amplitude across the arms with biceps transfer. CONCLUSIONS: Corticomotor excitability of the transferred biceps is modulated by arm posture and may contribute to strength outcomes after tendon transfer. Future work should determine whether modulating corticomotor excitability via posture promotes motor re-education during the rehabilitative period following surgery.