New pharmacological approaches against chronic bowel and bladder problems in paralytics

Spinal cord injury(SCI) leads generally to an irreversible loss of sensory functions and voluntary motor control below injury level. Cures that could repair SCI and/or restore voluntary walking have not been yet developed nor commercialized. Beyond the well-known loss of walking capabilities, most SCI patients experience also a plethora of motor problems and health concerns including specific bladder and bowel dysfunctions. Indeed, chronic constipation and urinary retention, two significant life-threatening complications, are typically found in patients suffering of traumatic(e.g., falls or car accidents) or non-traumatic SCI(e.g., multiple sclerosis, spinal tumors). Secondary health concerns associated with these dysfunctions include hemorrhoids, abdominal distention, altered visceral sensitivity, hydronephrosis, kidney failure, urinary tract infections, sepsis and, in some cases, cardiac arrest. Consequently, individuals with chronic SCI are forced to regularly seek emergency and critical care treatments when some of these conditions occur or become intolerable. Increasing evidence supports the existence of a novel experimental approach that may be capable of preventing the occurrence or severity of bladder and bowel problems. Indeed, recent findings in animal models of SCI have revealed that, despite paraplegia or tetraplegia, it remains possible to elicit episodes of micturition and defecation by acting pharmacologically or electrically upon specialized lumbosacral neuronal networks, namely the spinal or sacral micturition center(SMC) and lumbosacral defecation center(LDC). Daily activation of SMC and LDC neurons could potentially become, new classes of minimally invasive treatments(i.e., if orally active) against these dysfunctions and their many lifethreatening complications.

New avenues for reducing intensive care needs in patients with chronic spinal cord injury

Relatively soon after their accident, patients suffering a spinal cord injury(SCI) begin generally experiencing the development of significant, often life-threatening secondary complications. Many of which are associated with chronic physical inactivity-related immune function problems and increasing susceptibility to infection that repeatedly requires intensive care treatment. Therapies capable of repairing the spinal cord or restoring ambulation would normally prevent many of these problems but, as of now, there is no cure for SCI. Thus, management strategies and antibiotics remain the standard of care although antimicrobial resistance constitutes a significant challenge for patients with chronic SCI facing recurrent infections of the urinary tract and respiratory systems. Identifying alternative therapies capable of safe and potent actions upon these serious health concerns should therefore be considered a priority. This editorial presents some of the novel approaches currently in development for the prevention of specific infections after SCI. Among them, brain-permeable small molecule therapeutics acting centrally on spinal cord circuits that can augment respiratory capabilities or bladder functions. If eventually approved by regulatory authorities, some of these new avenues may potentially become clinically-relevant therapies capable of indirectly preventing the occurrence and/or severity of these lifethreatening complications in people with paraplegic or tetraplegic injuries.

Spectrum of neuropsychiatric symptoms in chronic post-stroke aphasia

BACKGROUND Neuropsychiatric symptoms(NPS)have been insufficiently examined in persons with aphasia(PWA)because most previous studies exclude participants with language and communication disorders.AIM To report a two-part study consisting of a literature review and an observational study on NPS in post-stroke aphasia.METHODS Study 1 reviewed articles obtained from PubMed,PsycINFO,Google Scholar and Cochrane databases after cross-referencing key words of post-stroke aphasia to NPS and disorders.Study 2 examined language deficits and activities of daily living in 20 PWA(median age:58,range:28-65 years;13 men)with the Western Aphasia Battery-Revised and the Barthel Index,respectively.Informants of these 20 PWA were proxy-evaluated with the Neuropsychiatric Inventory and domain-specific scales,including the Stroke Aphasia Depression Questionnaire-10 item version and the Starkstein Apathy Scale.In addition,an adapted version of the Hospital Anxiety and Depression Scale was directly administered to the PWA themselves.This observational study is based on the baseline assessment of an intervention clinical trial(EudraCT:2017-002858-36;ClinicalTrials.gov identifier:NCT04134416).RESULTS The literature review revealed a broad spectrum of NPS in PWA,including depression,anxiety,apathy,agitation/aggression,eating and sleep disorders,psychosis,and hypomania/mania.These findings alert to the need for improving assessment and treatment approaches of NPS taking into consideration their frequent occurrence in PWA.Study 2 showed that the 20 participants had mild-to-moderate aphasia severity and were functionally independent.A wide range of comorbid NPS was found in the post-stroke aphasic population(median number of NPS:5,range:1-8).The majority of PWA(75%)had depressive symptoms,followed by agitation/aggression(70%),irritability(70%),anxiety(65%)and appetite/eating symptoms(65%).Half of them also presented symptoms of apathy,whereas euphoria and psychotic symptoms were rare(5%).Domain-specific scales revealed that 45%of participants had apathy and 30%were diagnosed with depression and anxiety.CONCLUSION Concurrent NPS are frequent in the chronic period of post-stroke aphasia.Therefore,further research on reliable and valid assessment tools and treatment for this aphasic population is strongly warranted.

Acupuncture in living liver and kidney donors: a feasibility study

Objective: The purpose of this study was to test the feasibility of integrating acupuncture into the routine care of living liver and kidney donors during the process of donation and recovery.Methods: This is a pilot study on the feasibility of a brief acupuncture intervention for living liver and kidney donors. Participants received acupuncture immediately prior to organ donation surgery, every day as inpatients, while recovering from donation, and at a 2-week follow-up. Prior to surgery, questionnaires were completed on acupuncture outcome expectations and the State–Trait Anxiety Inventory. After participating, those who received acupuncture provided feedback. Following the active intervention, a retrospective chart review was conducted, using donors who did not receive acupuncture as a comparison cohort.Results: Forty donor candidates were approached and recruited, 32 consented and ultimately 25 donors participated in the acupuncture intervention(15 of kidney, 10 of liver), 68% female, and 88% Caucasian;only one had prior experience with acupuncture. Participants received an average of 4 sessions while inpatient(range 2–8). Those who expected acupuncture to be more helpful prior to the intervention reported lower inpatient pain scores(P = 0.04). Qualitative feedback from patients was predominantly positive,indicating acupuncture was helpful for relaxation and pain. However, a few patients reported feeling overburdened during postdonation recovery, and that the study was viewed as additional obligation.Conclusion: Preliminary findings suggest it is feasible to integrate acupuncture into inpatient recovery for living organ donation. Tailoring interventions to the specific needs of patients is important to address ongoing concerns. Larger studies are needed to further ascertain benefits of peri-operative acupuncture.

Animal models of Parkinson’s disease:bridging the gap between disease hallmarks and research questions

Parkinson’s disease(PD)is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms.More than 200 years after its first clinical description,PD remains a serious affliction that affects a growing proportion of the population.Prevailing treatments only alleviate symptoms;there is still neither a cure that targets the neurodegenerative processes nor therapies that modify the course of the disease.Over the past decades,several animal models have been developed to study PD.Although no model precisely recapitulates the pathology,they still provide valuable information that contributes to our understanding of the disease and the limitations of our treatment options.This review comprehensively summarizes the different animal models available for Parkinson’s research,with a focus on those induced by drugs,neurotoxins,pesticides,genetic alterations,α-synuclein inoculation,and viral vector injections.We highlight their characteristics and ability to reproduce PD-like phenotypes.It is essential to realize that the strengths and weaknesses of each model and the induction technique at our disposal are determined by the research question being asked.Our review,therefore,seeks to better aid researchers by ensuring a concrete discernment of classical and novel animal models in PD research.

Focus-tunable microscope for imaging small neuronal processes in freely moving animals

Miniature single-photon microscopes have been widely used to image neuronal assemblies in the brain of freely moving animals over the last decade. However,these systems have important limitations for imaging in-depth fine neuronal structures. We present a subcellular imaging single-photon device that uses an electrically tunable liquid crystal lens to enable a motion-free depth scan in the search of such structures. Our miniaturized microscope is compact (10 mm×17 mm×12 mm) and lightweight (≈1.4 g),with a fast acquisition rate (30–50 frames per second),high magnification (8.7×),and high resolution (1.4μm) that allow imaging of calcium activity of fine neuronal processes in deep brain regions during a wide range of behavioral tasks of freely moving mice.