Plasticity-Induced Effects of Theta Burst Transcranial Ultrasound Stimulation in Parkinson's Disease.

BACKGROUND: Low-intensity transcranial ultrasound stimulation (TUS) is a noninvasive brain stimulation (NIBS) technique with high spatial specificity. Previous studies showed that TUS delivered in a theta burst pattern (tbTUS) increased motor cortex (MI) excitability up to 30 minutes due to long-term potentiation (LTP)-like plasticity. Studies using other forms of NIBS suggested that cortical plasticity may be impaired in patients with Parkinson's disease (PD). OBJECTIVE: The aim was to investigate the neurophysiological effects of tbTUS in PD patients off and on dopaminergic medications compared to healthy controls. METHODS: We studied 20 moderately affected PD patients in on and off dopaminergic medication states (7 with and 13 without dyskinesia) and 17 age-matched healthy controls in a case-controlled study. tbTUS was applied for 80 seconds to the MI. Motor-evoked potentials (MEP), short-interval intracortical inhibition (SICI), and short-interval intracortical facilitation (SICF) were recorded at baseline, and at 5 minutes (T5), T30, and T60 after tbTUS. Motor Unified Parkinson's Disease Rating Scale (mUPDRS) was measured at baseline and T60. RESULTS: tbTUS significantly increased MEP amplitude at T30 compared to baseline in controls and in PD patients on but not in PD patients off medications. SICI was reduced in PD off medications compared to controls. tbTUS did not change in SICI or SICF. The bradykinesia subscore of mUPDRS was reduced at T60 compared to baseline in PD on but not in the off medication state. The presence of dyskinesia did not affect tbTUS-induced plasticity. CONCLUSIONS: tbTUS-induced LTP plasticity is impaired in PD patients off medications and is restored by dopaminergic medications. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Safety and efficacy of transcranial direct current stimulation in upper extremity rehabilitation after tetraplegia: protocol of a multicenter randomized, clinical trial.

STUDY DESIGN: A multisite, randomized, controlled, double-blinded phase I/II clinical trial. OBJECTIVE: The purpose of this clinical trial is to evaluate the safety, feasibility and efficacy of pairing noninvasive transcranial direct current stimulation (tDCS) with rehabilitation to promote paretic upper extremity recovery and functional independence in persons living with chronic cervical spinal cord injury (SCI). SETTING: Four-site trial conducted across Cleveland Clinic, Louis Stokes Veterans Affairs Medical Center of Cleveland and MetroHealth Rehabilitation Rehabilitation Institute of Ohio, and Kessler Foundation of New Jersey. METHODS: Forty-four adults (age ≥18 years) with tetraplegia following cervical SCI that occurred ≥1-year ago will participate. Participants will be randomly assigned to receive anodal tDCS or sham tDCS given in combination with upper extremity rehabilitation for 15 sessions each over 3-5 weeks. Assessments will be made twice at baseline separated by at least a 3-week interval, once at end-of-intervention, and once at 3-month follow-up. PRIMARY OUTCOME MEASURE(S): Primary outcome measure is upper extremity motor impairment assessed using the Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP) scale. Functional abilities will be assessed using Capabilities of Upper Extremity-Test (CUE-T), while functional independence and participation restrictions will be evaluated using the self-care domain of Spinal Cord Independent Measure (SCIM), and Canadian Occupational Performance Measure (COPM). SECONDARY OUTCOME MEASURES: Treatment-associated change in corticospinal excitability and output will also be studied using transcranial magnetic stimulation (TMS) and safety (reports of adverse events) and feasibility (attrition, adherence etc.) will also be evaluated. TRIAL REGISTRATION: ClincalTrials.gov identifier NCT03892746. This clinical trial is being performed at four sites within the United States: Cleveland Clinic (lead site), Louis Stokes Cleveland Veterans Affairs Medical Center (VAMC) and MetroHealth Rehabilitation Institute in Ohio, and Kessler Foundation in New Jersey. The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702-5014 is the awarding and administering acquisition office.

Helmet Usage Reduces Serious Head Injury Without Decreasing Concussion After Bicycle Riders Crash.

BACKGROUND: The importance of bicycle helmets in reducing injuries is unclear. Our center receives a disproportionate number of bicycle crash victims. We sought to evaluate the types of injuries observed and the role of helmets in reducing head injuries. MATERIALS AND METHODS: We evaluated demographic data and compared injuries between bicycle riders that crashed with and without helmets over a 9-year period. Categorical variables were compared using linear regression methods and nominal variables using ANOVA. Differences were considered significant for P ≤ 0.05. RESULTS: There were 906 patients evaluated, 701 with helmets (77%) and 205 (23%) without helmets. The mean Injury Severity Score was 9.3 ± 6.4. The most common injuries were concussion (n = 385), rib fractures (n = 154), clavicle fractures (n = 139), facial fractures (n = 102), and cervical spine fractures (n = 89). There was no significant difference in the number of patients with a concussion in riders with or without helmets, [299/701, 42.6% versus 86/205, 42.0%, respectively, (P = NS)]. In helmet versus no helmet riders, there were significantly fewer patients with facial fractures, [67/701, 9.5%, versus 35/205, 17.0%, respectively, (P = 0.003)], skull fractures [8/701, 1.1% versus 9/205, 4.4%, respectively, (P = 0.003)], and serious head injuries [6/701, 0.85% versus 8/205, 3.9%, respectively, (P = 0.002)]. CONCLUSIONS: Helmeted patients involved in bicycle crashes are less likely to sustain a serious head injury, a skull fracture, or facial fractures compared to riders without helmets. The most common injury in patients with a bicycle crash is a concussion. Helmets did not prevent concussion after bicycle rider's crash in our patient population.

Measurement error and reliability of TMS metrics collected from biceps and triceps in individuals with chronic incomplete tetraplegia.

Transcranial magnetic stimulation (TMS) is used to investigate corticomotor neurophysiology associated with functional recovery in individuals with spinal cord injury (SCI). There is insufficient evidence about test-retest measurement properties of TMS in SCI. Therefore, we investigated test-retest agreement and reliability of TMS metrics representing corticomotor excitability, output, gain, map (representation), and inhibition in individuals with cervical SCI. We collected TMS metrics from biceps and triceps muscles because of the relevance of this proximal muscle pair to the cervical SCI population. Twelve individuals with chronic C3-C6 SCI participated in two TMS sessions separated by ≥ 2 weeks. Measurement agreement was evaluated using t tests, Bland-Altman limits of agreement and relative standard error of measurement (SEM%), while reliability was investigated using intra-class correlation coefficient (ICC) and concordance correlation coefficient (CCC). We calculated the smallest detectable change for all TMS metrics. All TMS metrics except antero-posterior map coordinates and corticomotor inhibition were in agreement upon repeated measurement though limits of agreement were generally large. Measures of corticomotor excitability, output and medio-lateral map coordinates had superior agreement (SEM% < 10). Metrics representing corticomotor excitability, output, and inhibition had good-to-excellent reliability (ICC/CCC > 0.75). The smallest detectable change for TMS metrics was generally high for a single individual, but this value reduced substantially with increase in sample size. We recommend use of corticomotor excitability and recruitment curve area owing to their superior measurement properties. A modest group size (20 or above) yields more stable measurements, which may favor use of TMS metrics in group level modulation after SCI.

Economic Burden of Osteoporosis-Related Fractures in the US Medicare Population.

BACKGROUND: Osteoporosis-related fractures are an important public health burden. OBJECTIVE: To examine health care costs in Medicare patients with an osteoporosis-related fracture. METHODS: Medicare fee-for-service members with an osteoporosis-related fracture between January 1, 2010, to September 30, 2014 were included. A nonfracture comparator group was selected by propensity score matching. Generalized linear models using a gamma distribution were used to compare costs between fracture and nonfracture cohorts. RESULTS: A total of 885 676 Medicare beneficiaries had fracture(s) and met inclusion criteria. Average age was 80.5 (±8.4) years; 91% were White, and 94% female. Mean all-cause costs were greater in the fracture vs nonfracture cohort ($47 163.25 vs $16 034.61) overall and for men ($52 273.79 vs $17 352.68). The highest mean costs were for skilled nursing facility ($29 216), inpatient costs ($24 190.19), and hospice care ($20 996.83). The highest incremental costs versus the nonfracture cohort were for hip ($71 057.83 vs $16 807.74), spine ($37 543.87 vs $16 860.49), and radius/ulna ($24 505.27 vs $14 673.86). Total medical and pharmacy costs for patients who experienced a second fracture were higher compared with those who did not ($78 137.59 vs $44 467.47). Proportionally more patients in the fracture versus nonfracture cohort died (18% vs 9.3%), with higher death rates among men (20% vs 11%). CONCLUSION AND RELEVANCE: The current findings suggest a significant economic burden associated with fractures. Early identification and treatment of patients at high risk for fractures is of paramount importance for secondary prevention and reduced mortality.

1,3-Butadiene, styrene and lymphohaematopoietic cancers among North American synthetic rubber polymer workers: exposure-response analyses.

OBJECTIVE: To evaluate exposure-response between 1,3-butadiene, styrene and lymphohaematopoietic cancers in an updated cohort of workers at six North American plants that made synthetic rubber polymers. METHODS: Employees were followed from 1943 through 2009 to determine mortality outcomes. Cox regression analyses estimated rate ratios (RRs) and 95% CIs by quartile of cumulative exposure to butadiene or styrene, measured in parts per million-years (ppm-years), and exposure-response trends for all leukaemia, lymphoid leukaemia, myeloid leukaemia, acute myeloid leukaemia, non-Hodgkin's lymphoma (NHL), multiple myeloma and all B-cell malignancies. RESULTS: Among 21 087 workers, adjusted RRs for butadiene and all leukaemia (132 deaths) rose with increasing exposure, with an RR of 2.53 (95% CI 1.37 to 4.67) in the highest exposure quartile (≥363.64 ppm-years), and the exposure-response trend was statistically significant for all leukaemia (p=0.014) and for lymphoid leukaemia (52 deaths, p=0.007). Styrene exposure-response trends for all leukaemia and lymphoid leukaemia were less consistent than those for butadiene. Cumulative exposures to butadiene and styrene were not associated consistently with myeloid leukaemias or the B-cell malignancies, NHL and multiple myeloma. CONCLUSIONS: We confirmed a positive exposure-response relationship between butadiene and all leukaemia among workers, most of whom had coexposure to styrene. Results supported an association between butadiene and lymphoid leukaemia, but not myeloid leukaemia, and provided little evidence of any association of butadiene or styrene exposures with major subtypes of B-cell malignancies other than lymphoid leukaemia, including NHL and multiple myeloma.

The effects of light touch on gait and dynamic balance during normal and tandem walking in individuals with an incomplete spinal cord injury.

STUDY DESIGN: Prospective cross-sectional study OBJECTIVES: To investigate the effect of adding haptic input during walking in individuals with incomplete spinal cord injury (iSCI). SETTING: Research laboratory. METHODS: Participants with iSCI and age- and sex-matched able-bodied (AB) individuals walked normally (SCI n = 18, AB n = 17) and in tandem (SCI n = 12, AB n = 17). Haptic input was added through light touch on a railing. Step parameters, and mediolateral and anterior-posterior margins of stability (means and standard deviations) were calculated. Surface electromyography data were collected bilaterally from the tibialis anterior (TA), soleus (SOL), and gluteus medius (GMED) and integrated over a stride. Repeated measures ANOVAs examined within- and between-group differences (α = 0.05). Cutaneous and proprioceptive sensation of individuals with iSCI were correlated to changes in outcome measures that were affected by haptic input. RESULTS: When walking normally, adding haptic input decreased stride velocity, step width, stride length, MOSML, MOSML_SD, MOSAP, and MOSAP_SD, and increased GMED activity on the limb opposite the railing. During tandem walking, haptic input had no effect; however, individuals with iSCI had a larger step width SD and MOSML_SD compared with the AB group. Sensory abilities of individuals with iSCI were not correlated to any of the outcome measures that significantly changed with added haptic input. CONCLUSIONS: Added haptic input improved balance control during normal but not in tandem walking. Sensory abilities did not impact the use of added haptic input during walking.

Duration of Bisphosphonate Drug Holidays and Associated Fracture Risk.

BACKGROUND: Discontinuation of bisphosphonates (BP) or a "drug holiday" after several years of treatment is increasingly common. However, the association of drug holiday duration with future fracture risk is unclear. OBJECTIVES: We evaluated the rate of fracture in relation to various lengths of drug holidays among women receiving long-term BP therapy. RESEARCH DESIGN: Observational cohort study using US Medicare data 2006-2016. Incidence rates (IRs) and Cox proportional hazards models were used to evaluate the rate and adjusted hazard ratios (aHRs) controlling for potential confounders. SUBJECTS: Women aged 65 years and above enrolled in fee-for-service Medicare who had been adherent (≥80%) to alendronate, risedronate, or zoledronate for ≥3 years. MEASURES: Hip, humerus, distal forearm, and clinical vertebral fracture. RESULTS: Among 81,427 eligible women observed for a median (interquartile range) of 4.0 (2.5, 5.3) years, 28% of women underwent a drug holiday. In the alendronate cohort (73% overall), the IR of hip fracture among women who discontinued BP for >2 years was 13.2 per 1000 person-years. Risk was increased (aHR=1.3, 1.1-1.4) versus continuing therapy (IR=8.8, referent). Rates were elevated for humerus fracture with discontinuation >2 years (aHR=1.3, 1.1-1.66) and for clinical vertebral fracture with discontinuation >2 years (aHR=1.2, 1.1-1.4). Results were similar for risedronate, zoledronate, and ibandronate for hip and clinical vertebral fracture. CONCLUSION: Discontinuing alendronate beyond 2 years was associated with increased risk of hip, humerus, and clinical vertebral fractures.

Comparison of the species-sensitive effects of different dosages of calcium and verapamil on gentamicin-induced nephrotoxicity in rats and rabbits.

AIM: To compare the effects of different dosages of calcium and verapamil on gentamicin-induced nephrotoxicity in rats and rabbits. MATERIALS AND METHODS: Rabbits and rats of either sex in weight range of 1.5-2.5 kg and 175-225 g, respectively were used in study. Gentamicin 80 mg/kg i.m., calcium carbonate 0.5 g/kg/day oral, calcium carbonate 1.0 g/kg/day oral, and verapamil 7 mg/kg/day i.m. were administered for 6 days in either species containing 7 groups. Blood urea nitrogen (BUN), serum creatinine and, urine protein levels were assessed on day 0 and day 7 for kidney function. The animals were sacrificed on day 7 for histopathplogical examination and kidney superoxide dismutase levels (SOD) were measured. Statistical analysis was done using student's unpaired t-test, analysis of variance (ANOVA) and Wilcoxon Rank Sum test. P-value less than 0.05 was considered significant. RESULTS: The results showed that calcium was able to reverse significantly increased BUN, serum creatinine, urine protein, and reduced kidney SOD levels in gentamicin-treated nephrotoxic rats or rabbits in a dose-dependent manner while verapamil had no protective or nephrotoxic effect. CONCLUSION: Calcium 0.5 g/kg/day and 1.0 g/kg/day were able to reverse tubular necrosis and mesangial proliferation in gentamicin-treated nephrotoxic animals. There was no species-sensitive variation in reversal of nephrotoxicity by calcium in rats and rabbits.

Comparative effectiveness of Denosumab vs alendronate among postmenopausal women with osteoporosis.

Although clinical trials have shown that denosumab significantly increases bone mineral density at key skeletal sites more than oral bisphosphonates, evidence is lacking from head-to-head randomized trials evaluating fracture outcomes. This retrospective cohort study uses administrative claims data from Medicare fee-for service beneficiaries to evaluate the comparative effectiveness of denosumab versus alendronate in reducing fracture risk among women with postmenopausal osteoporosis (PMO) in the US. Women with PMO ≥ 66 years of age with no prior history of osteoporosis treatment, who initiated denosumab (n = 89 115) or alendronate (n = 389 536) from 2012 to 2018, were followed from treatment initiation until the first of a specific fracture outcome, treatment discontinuation or switch, end of study (December 31, 2019), or other censoring criteria. A doubly robust inverse-probability of treatment and censoring weighted function was used to estimate the risk ratio associated with the use of denosumab compared with alendronate for hip, nonvertebral (NV; includes hip, humerus, pelvis, radius/ulna, other femur), non-hip nonvertebral (NHNV), hospitalized vertebral (HV), and major osteoporotic (MOP; consisting of NV and HV) fractures. Overall, denosumab reduced the risk of MOP by 39%, hip by 36%, NV by 43%, NHNV by 50%, and HV fractures by 30% compared with alendronate. Denosumab reduced the risk of MOP fractures by 9% at year 1, 12% at year 2, 18% at year 3, and 31% at year 5. An increase in the magnitude of fracture risk reduction with increasing duration of exposure was also observed for other NV fracture outcomes. In this cohort of almost half-a-million treatment-naive women with PMO, we observed clinically significant reductions in the risk of MOP, hip, NV, NHNV, and HV fractures for patients on denosumab compared with alendronate. Patients who remained on denosumab for longer periods of time experienced greater reductions in fracture risk.

Osteoporosis-related fractures can have a significant impact on the health and quality of life of women with postmenopausal osteoporosis (PMO), as well as pose a significant burden to society. Although clinical trials have shown that denosumab is more effective at increasing bone mineral density compared to alendronate, there is a lack of evidence evaluating the fracture risk between these two commonly used osteoporosis therapies. In this study using Medicare claims data for almost 500 000 women with PMO with no prior history of osteoporosis medication use, we compared the risk of fracture, an important outcome to patients and health care providers, between denosumab and alendronate. Advanced analytic methods were implemented to ensure the study results were valid and were not unduly influenced by biases common in observational studies. We observed clinically meaningful reductions (from 30% up to 50%) in the risk of hip, nonvertebral, non-hip nonvertebral, hospitalized vertebral, and major osteoporotic fractures for patients treated with denosumab compared with alendronate. Patients who remained on denosumab for longer periods of time experienced greater reductions in fracture risk than those who remained on alendronate.

Caregivers' Perspective on Successful Health Care Transition Outcomes for Adolescents and Young Adults With Special Health Care Needs.

PURPOSE: There is limited caregiver-reported evidence determining health care transition (HCT) outcomes for their adolescents/young adults with special health care needs (AYA-SHCN). A subcommittee of the International and Interdisciplinary Healthcare Transition Research Consortium aimed to identify multidimensional outcomes of a successful HCT among AYA-SHCN based on parents/caregivers' perspectives. METHODS: After literature review and expert interviews, a three-stage Delphi process identified HCT outcomes based on parents/caregivers' perspectives. Participants were parents/caregivers of patients attending the Victory Junction Therapeutic Camp and a nationally representative sample from Cint Healthcare Digital Solutions Platform. The cumulative 272 responses collected on a Health Insurance Portability and Accountability Act-compliant web-based engine (Qualtrics) rated potential HCT outcomes by level of importance on a Likert scale from 1 (not important) to 9 (very important) and narrowed in subsequent iterations. RESULTS: The Delphi process included 127 (Stage 1), 82 (Stage 2), and 63 (Stage 3) parents/caregivers. The initial 25 HCT outcomes were narrowed to 13, across four major domains: coping/satisfaction, behavioral, structural, and HCT/healthcare-focused outcomes. The top outcome was "My child takes their medications as prescribed." Several traditionally considered important outcomes for HCT were eliminated. DISCUSSION: Thirteen HCT outcomes for AYA-SHCN were identified in four major domains: coping/satisfaction, behavioral, structural, and HCT/healthcare focused. Future research in larger samples would allow stratification to represent diverse patients and caregiver populations. Identifying international consensus-derived outcomes among parents/caregivers is imperative for the evaluation of HCT preparation strategies that ensure appropriate support for diverse AYA-SHCN and their families during this process and enable implementation of the most effective interventions.

Corticospinal inhibition investigated in relation to upper extremity motor function in cervical spinal cord injury.

OBJECTIVE: Corticospinal inhibitory mechanisms are relevant to functional recovery but remain poorly understood after spinal cord injury (SCI). Post-injury characteristics of contralateral silent period (CSP), a measure of corticospinal inhibition evaluated using transcranial magnetic stimulation (TMS), is inconsistent in literature. We envisioned that investigating CSP across muscles with varying degrees of weakness may be a reasonable approach to resolve inconsistencies and elucidate the relevance of corticospinal inhibition for upper extremity function following SCI. METHODS: We studied 27 adults with chronic C1-C8 SCI (age 48.8 ± 16.1 years, 3 females) and 16 able-bodied participants (age 33.2 ± 11.8 years, 9 females). CSP characteristics were assessed across biceps (muscle power = 3-5) and triceps (muscle power = 1-3) representing stronger and weaker muscles, respectively. We assessed functional abilities using the Capabilities of the Upper Extremity Test (CUE-T). RESULTS: Participants with chronic SCI had prolonged CSPs for biceps but delayed and diminished CSPs for triceps compared to able-bodied participants. Early-onset CSPs for biceps and longer, deeper CSPs for triceps correlated with better CUE-T scores. CONCLUSIONS: Corticospinal inhibition is pronounced for stronger biceps but diminished for weaker triceps muscle in SCI indicating innervation relative to the level of injury matters in the study of CSP. SIGNIFICANCE: Nevertheless, corticospinal inhibition or CSP holds relevance for upper extremity function following SCI.

Comparison of topical anesthesia and peribulbar anesthesia for 23-gauge vitrectomy without sedation.

PURPOSE: To compare the safety and efficacy of topical anesthesia versus peribulbar anesthesia for 23-gauge vitrectomy without sedation. METHODS: Selected group of 60 patients with vitreous hemorrhage were divided into 2 groups and underwent 23-gauge vitrectomy. Group 1 used topical anesthesia, whereas Group 2 used peribulbar anesthesia. A 5-point Visual Analogue Scale was used to assess patients' pain score and surgeon's ease while operating. Any complications thereof were made note of. RESULTS: Mean overall patients' pain scores were 1.77 ± 0.50 in Group 1 and 1.77 ± 0.43 in Group 2. Surgeon's comfort score was recorded as 0.3 ± 0.53 and 0.17 ± 0.38 in Groups 1 and 2, respectively. Mean surgical time was 33.7 ± 7.1 minutes and 30.1 ± 6.2 minutes in Groups 1 and 2, respectively. These means were not statistically significant (P > 0.05). No patient required sedation or anesthesia supplementation. Group 1 patients reported maximum pain during trocar entry, whereas Group 2 reported maximum pain during block. Group 2 patients also reported significant conjunctival chemosis and lid edema postblock. CONCLUSION: Topical anesthesia without any sedation is a viable option, comparable to peribulbar block, for performing vitrectomy in selected group of patients requiring vitrectomy and thus avoiding complication of injection anesthesia and quicker postoperative recovery.

Retcam fluorescein gonioangiography: a new modality for early detection of angle neovascularization in diabetic retinopathy.

PURPOSE: To evaluate the role of Retcam fluorescein gonioangiography in detecting neovascularization of the angle and correlate the same with gonioscopy in diabetic retinopathy. METHODS: One hundred and fifty eyes of 150 patients (25 each of mild, moderate, severe, very severe nonproliferative diabetic retinopathy (NPDR) proliferative diabetic retinopathy (PDR); and PDR with high-risk characteristics) were recruited. They underwent complete ocular examination including applanation tonometry, gonioscopy, Retcam fluorescein gonioangiography, and fundus fluorescein angiography. RESULTS: Using Retcam fluorescein gonioangiography, of 150 eyes neovascularization of the angle was detected in 37 eyes (24.66%) compared with 22 eyes (14.66%) on gonioscopy (P = 0.04). Small newly formed vessels were evident only with Retcam fluorescein gonioangiography. In 10 of 50 patients (20%) with severe/very severe NPDR, angle neovascularization was appreciable on Retcam fluorescein angiography compared with 5 patients (10%) on gonioscopy. Similarly, 25 of 50 patients (50%) with PDR/PDR with high-risk characteristics had neovascularization of the angle on Retcam gonioangiography compared with 17 (34%) on gonioscopy. CONCLUSION: Retcam fluorescein gonioangiography is a novel technique for early detection of angle neovascularization in diabetic retinopathy and hence preventing progression to neovascular glaucoma. The objective nature of this test helps in precise decision making compared with gonioscopy for early intervention especially in cases of pre-PDR.

Unilateral persistent fetal vasculature coexisting with anterior segment dysgenesis.

Persistent fetal vasculature (PFV) is a common congenital developmental anomaly of the eye which results from failure of the embryological primary vitreous and hyaloid vasculature to regress by the time of birth (Int Ophthalmol Clin 48: 53-62, 2008). Typically, it is divided into anterior, posterior or combined types and is characterized by the presence of a vascular stalk located between the optic disc and the posterior lens capsule (Int Ophthalmol Clin 48: 53-62, 2008). Although it has been reported to manifest itself differently, in our case it presented in a microphthalmic eye as anterior segment dysgenesis with broad-based mid-peripheral synechiae, posterior embryotoxon, iridoschisis, ectropion uveae, hypotony and subluxated cataractous lens with a taut anterior hyaloid face which are rare associations with PFV.

Non-fragile synchronization of BAM neural networks with randomly occurring controller gain fluctuation.

In this research, a non-fragile synchronization of bidirectional association memory (BAM) delayed neural networks is taken into consideration. The controller gain fluctuation seems in a very random manner, that obeys sure Bernoulli distributed noise sequences. Delay dependent criteria are derived to confirm the asymptotic stability of the BAM delayed neural networks. The non-fragile controller are often obtained by determination a collection of linear matrix inequalities (LMIs). A simulation example is used to demonstrate the efficiency of the developed control.

Mechanisms of theta burst transcranial ultrasound induced plasticity in the human motor cortex.

BACKGROUND: Transcranial ultrasound stimulation (TUS) is a novel non-invasive brain stimulation technique with high depth penetrance and spatial resolution. Theta-burst TUS (tbTUS) is a plasticity-inducing protocol which increases motor cortical excitability for up to 30 min following 80s of sonication. While this protocol may have therapeutic potential for the treatment of psychiatric and neurological disorders, the mechanisms of action of TUS remain unclear. OBJECTIVE: We conducted the first pharmacological study to examine the mechanisms of TUS in human primary motor cortex. By administering brain-active drugs with known mechanisms of action, we aimed to elucidate the mechanisms of tbTUS. METHODS: Fourteen healthy subjects participated in a within-subjects randomized, double-blind, cross-over study with five visits. At each visit, one of four study drugs (carbamazepine - Na+ channel blocker, nimodipine - L-type Ca2+ channel blocker, lorazepam - positive allosteric modulator of gamma-aminobutyric acid (GABA) type A receptor, dextromethorphan - N-methyl-d-aspartate receptor antagonist) or placebo was administered in random order, followed by tbTUS. RESULTS: The plasticity effects of tbTUS on motor cortex excitability measured by motor-evoked potential amplitudes elicited by transcranial magnetic stimulation were reduced by all study drugs compared to placebo. CONCLUSION: tbTUS may induce NMDA-dependent synaptic plasticity since the effects are blocked by increased GABAA receptor activities and voltage-gated Na+ and Ca2+ channels blockers. These results are consistent with the hypotheses that tbTUS induced long-term potentiation-like mechanisms and that TUS involves activation of mechanosensitive Na+ and Ca2+ channels. Alternatively, non-specific pharmacologically induced changes in excitatory/inhibitory balance might have interfered with the effects of tbTUS.

Visual and vestibular integration in Parkinson's disease while walking.

Postural control requires effective sensory integration. People with Parkinson's disease (PD) are reported to have impaired visual and vestibular perception. While self-motion perception is a key aspect of locomotion, visual-vestibular integration has not been directly characterized in people with PD during gait. We compared the ability of people with PD and healthy older adults (OA) to integrate multi-sensory information during straight-line walking in response to visual and vestibular perturbations, using continuous translations of the visual surround and galvanic vestibular stimulation within a virtual reality environment. We measured their endpoint deviations from midline and changes in gait parameters. We found that people with PD deviated more than OA when walking in a dark environment but did not show differences in deviations when walking in a virtual room with visual information. With visual and vestibular perturbations, people with PD did not differ from OA in endpoint deviations nor variabilities. However, people with PD did not adopt a more cautious gait when GVS was applied in a virtual room, unlike OA. Overall, we showed that people with mild PD did not perform worse than OA but did show differences in gait patterns, suggesting that visual-vestibular integration is relatively preserved during gait in PD.

Comparability of Osteoporosis Treatment Groups Among Female Medicare Beneficiaries in the United States.

It is often difficult to obtain valid estimates of comparative treatment effectiveness and safety owing to differences across patient populations taking different medications in the real world. One approach for assessing comparability between treatment groups in effectiveness studies is to use negative control outcomes (NCOs). NCOs share similar sources of bias with the primary outcomes but have no plausible causal relationship to the treatment of interest. Observing differences in the risk of NCOs thus provides evidence for residual confounding between groups. This retrospective study assessed the comparability of postmenopausal women, treated with osteoporosis medications with various mechanisms of action such as denosumab (receptor activator of nuclear factor κB ligand [RANKL] inhibitor), zoledronic acid (bisphosphonate derivative), or oral bisphosphonates including alendronate. Administrative claims data were extracted from the US Centers for Medicare and Medicaid Services' Chronic Condition Warehouse database (May 2010-December 2016). Propensity scores were used to match denosumab patients 1:1 to comparators. Four nonfracture NCOs and three early fracture NCOs (before substantial biologic effects of treatment would be expected) were assessed over 1-year and 3-month follow-up periods, respectively. According to comparability decision rules established a priori, patients initiating denosumab were comparable to those initiating zoledronic acid or alendronate, irrespective of prior osteoporosis treatment experience. Among new users, new switchers, and in the historical fracture subgroup, no meaningful differences were observed in the cumulative incidence of the seven NCOs comparing denosumab to zoledronic acid. This empirical examination can assist in the selection of appropriate comparator groups for future comparability research using real-world data. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Mortality following bone metastasis and skeletal-related events among women with breast cancer: a population-based analysis of U.S. Medicare beneficiaries, 1999-2006.

The aim of the study is to quantify the impact of bone metastasis and skeletal-related events (SREs) on mortality in older breast cancer patients. Using the linked Surveillance, Epidemiology and End Results-Medicare database, we identified women aged 65 years or older diagnosed with breast cancer between July 1, 1999 and December 31, 2005 and followed them to determine deaths occurring through December 31, 2006. We classified patients as having possible bone metastasis and SREs using discharge diagnoses from inpatient claims and diagnoses paired with procedure codes from outpatient claims. We used Cox regression to estimate mortality hazards ratios (HR) among women with bone metastasis with or without SRE, compared with women without bone metastasis. Among 98,260 women with breast cancer (median follow-up, 3.3 years), 7,189 (7.3%) had bone metastasis either at breast cancer diagnosis (1.5%) or during follow-up (5.8%). SREs occurred in 3,319 (46%) of women with bone metastasis. HRs for risk of death were 4.9 (95% CI 4.7-5.1) and 6.2 (95% CI 5.9-6.5), respectively, for women with bone metastasis but no SRE and for women with bone metastasis plus SRE, compared with women without bone metastasis. In analyses restricted to women with bone metastasis, the adjusted HR was 1.5 (95% CI 1.4-1.6) for women with bone metastasis plus SRE, compared with women with bone metastasis but without SRE. Having a bone metastasis, as indicated by Medicare claims, was associated strongly with mortality among women with breast cancer. This association was stronger for bone metastasis complicated by SRE than for bone metastasis without SRE.