The Interactions of Temporal and Sensory Representations in the Basal Ganglia.

In rodents and primates, interval estimation has been associated with a complex network of cortical and subcortical structures where the dorsal striatum plays a paramount role. Diverse evidence ranging from individual neurons to population activity has demonstrated that this area hosts temporal-related neural representations that may be instrumental for the perception and production of time intervals. However, little is known about how temporal representations interact with other well-known striatal representations, such as kinematic parameters of movements or somatosensory representations. An attractive hypothesis suggests that somatosensory representations may serve as the scaffold for complex representations such as elapsed time. Alternatively, these representations may coexist as independent streams of information that could be integrated into downstream nuclei, such as the substantia nigra or the globus pallidus. In this review, we will revise the available information suggesting an instrumental role of sensory representations in the construction of temporal representations at population and single-neuron levels throughout the basal ganglia.

Burden of Stroke and Population-Attributable Fractions of Risk Factors in Latin America and the Caribbean.

Background Stroke burden characterization studies in low- and middle-income countries are scarce. We estimated the burden of stroke and its risk factors in Latin America and the Caribbean (LAC). Methods and Results We extracted GBD (Global Burden of Disease) study 2019 data on overall stroke and 3 subtypes (ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage) for 20 LAC countries. We estimated absolute and age-standardized rates of disability-adjusted life years, years of life lost, years lived with disability, and deaths. The population-attributable fractions of 17 risk factors were estimated. All analyses were performed at regional and national levels by stroke subtype, sex, and age subgroups. In 2019, the LAC region had the fourth largest stroke burden worldwide (6.8 million disability-adjusted life years), predominantly attributable to premature deaths (89.5% of disability-adjusted life years). Intracerebral hemorrhage was the primary cause of the overall stroke burden (42% of disability-adjusted life years), but ischemic stroke was the leading cause of disability (69% of total years lived with disability). Haiti and Honduras had the highest age-standardized rates. Older adults and men had the largest burdens, although women had the highest rate of disability. Socioeconomic development level did not influence the burden. The major risk factor clusters were metabolic (high systolic blood pressure [population-attributable fraction=53%] and high body mass index [population-attributable fraction=37%]), which were more influential in hemorrhagic events, women, and older adults. Household air pollution was an important risk factor in low-income countries in LAC. Conclusions The stroke burden and stroke-related mortality in LAC are higher than the worldwide averages. However, stroke is a highly preventable disease in this region. Up to 90% of the burden could be reduced by targeting 2 modifiable factors: blood pressure and body mass index. Further research and implementation of primary and secondary prevention interventions are needed, as well as integrated national stroke care programs for acute, subacute, and rehabilitation management in LAC.

Altered Sensory Representations in Parkinsonian Cortical and Basal Ganglia Networks.

In parkinsonian conditions, network dynamics in the cortical and basal ganglia circuits present abnormal oscillations and periods of high synchrony, affecting the functionality of multiple striatal regions including the sensorimotor striatum. However, it is still unclear how these altered dynamics impact on sensory processing, a key feature for motor control that is severely impaired in parkinsonian patients. A major confound is that pathological dynamics in sensorimotor networks may elicit unspecific motor responses that may alter sensory representations through sensory feedback, making it difficult to disentangle motor and sensory components. To address this issue, we studied sensory processing using an anesthetized model with robust sensory representations throughout cortical and basal ganglia sensory regions and limited motor confounds in control and hemiparkinsonian rats. A general screening of sensory-evoked activity in large populations of neurons recorded in the primary sensory cortex (S1), dorsolateral striatum (DLS) and substantia nigra pars reticulata (SNr) revealed increased excitability and altered sensory representations in the three regions. Further analysis revealed uncoordinated population dynamics between DLS and S1/SNr. Finally, DLS lesions in hemiparkinsonian animals partially recovered population dynamics and execution in the rotarod.

Sensory representations in the striatum provide a temporal reference for learning and executing motor habits.

Previous studies indicate that the dorsolateral striatum (DLS) integrates sensorimotor information from cortical and thalamic regions to learn and execute motor habits. However, the exact contribution of sensory representations to this process is still unknown. Here we explore the role of the forelimb somatosensory flow in the DLS during the learning and execution of motor habits. First, we compare rhythmic somesthetic representations in the DLS and primary somatosensory cortex in anesthetized rats, and find that sequential and temporal stimuli contents are more strongly represented in the DLS. Then, using a behavioral protocol in which rats developed a stereotyped motor sequence, functional disconnection experiments, and pharmacologic and optogenetic manipulations in apprentice and expert animals, we reveal that somatosensory thalamic- and cortical-striatal pathways are indispensable for the temporal component of execution. Our results indicate that the somatosensory flow in the DLS provides the temporal reference for the development and execution of motor habits.

Efficacy and Safety of 0.6% Pazufloxacin Ophthalmic Solution Versus Moxifloxacin 0.5% and Gatifloxacin 0.5% in Subjects with Bacterial Conjunctivitis: A Randomized Clinical Trial.

PURPOSE: The purpose of this study was to evaluate the clinical efficacy and safety of a novel ophthalmic solution of pazufloxacin on the ocular surface of patients with bacterial conjunctivitis after 7 days of intervention. METHODS: This is a phase 2, double-blind, controlled, multicenter, clinical trial of 300 subjects, randomized to either a 3 dosing regimen of pazufloxacin 0.6% ophthalmic solution (twice a day [BID], n = 90; 3 times a day [TID], n = 76; 4 times a day [QID], n = 68), moxifloxacin 0.3% TID (n = 82), or gatifloxacin 0.5% TID (n = 72). Follow-up was set on days 0, 3, and 7. Assessments of ocular signs were performed, both anterior and posterior segments. The primary outcome measures included conjunctival culture and clinical signs. Safety variables included adverse events (AEs), lisamine green, fluorescein ocular surface stains, and clinical signs of tolerability. RESULTS: After intervention, bacterial eradication was reported in all groups: pazufloxacin BID 79%, pazufloxacin TID 84%, pazufloxacin QID 84%, moxifloxacin 80%, and gatifloxacin 82%. There were no significant differences between treatments. Similar results were reported in clinical remission: pazufloxacin BID 89%, pazufloxacin TID 98%, pazufloxacin QID 92%, moxifloxacin 91%, and gatifloxacin 92% (P = 0.03 comparing pazufloxacin BID vs. TID). There were no differences between female and male responses. The AEs were not related to the interventions. CONCLUSIONS: A simplified dosing regimen was selected to follow the development of ophthalmic pazufloxacin based on its efficacy and safety profile. Pazufloxacin, 1 drop 3 times daily, showed similar rates of bacterial eradication and clinical remission compared with other fluoroquinolones.

Contralateral Autologous Corneal Transplantation Experience in Mexico City.

PURPOSE: The aim of this study is to expand the limited knowledge regarding autologous contralateral penetrating keratoplasty. METHODS: We report the retrospective outcomes of patients who received autokeratoplasty and contralateral opaque corneas in the donor eye at a tertiary care ophthalmology hospital in Mexico City. RESULTS: Eleven patients received autokeratoplasty and contralateral opaque corneas in the donor eye at our center from 2010 to 2015. The mean patient age at the time of surgery was 58 years (range, 35-85 yrs), with 4 female and 7 male patients. There were no surgical or immediate postsurgical complications in the autokeratoplasty eye. However, 1 patient had expulsive hemorrhage in the sightless eye. Follow-up duration ranged from 11 to 65 months (mean, 26 mo). During follow-up, 3 of the autokeratoplasty procedures failed because of endothelial attenuation. Identified known risk factors for failure of the eye with visual potential included the presence of an Ahmed glaucoma drainage device in 7/11 patients (63%), history of glaucoma in 8/11 (72%), past heterologous penetrating keratoplasty in 2/11 (18%), Vogt-Koyanagi-Harada syndrome in 1/11 (9%), and 4-quadrant corneal vascularization in 1/11 (9%). CONCLUSIONS: Autokeratoplasty is a good choice in cases having high risk factors and when fresh corneal tissue is not available. This is the largest study describing outcomes of patients who underwent autokeratoplasty. This technique offers no risk of immune rejection and no need for immunosuppression treatment. This study reports a good prognosis in cases having high risk factors for failure.

Efficacy of a fixed combination of 0.09 % xanthan gum/0.1 % chondroitin sulfate preservative free vs polyethylene glycol/propylene glycol in subjects with dry eye disease: a multicenter randomized controlled trial.

BACKGROUND: Dry eye disease (DED) is multifactorial, affecting 5-34 % of the global adult population and reducing quality of life. The artificial tears or lubricants are the therapy most used for the treatment of DED, due to their low side effect profile, which attempt to modify the properties of the tear film. The aim of the present study was to evaluate the clinical efficacy of a fixed combination of xanthan gum and chondroitin sulfate preservative free on the ocular surface of patients with dry eye disease during 60 days of intervention. METHODS: A phase III, double-blind, masked, controlled, multicenter, clinical trial of 148 subjects, randomized to either a fixed combination of xanthan gum 0.09 % and chondroitin sulfate 0.1 % (XG/CS) ophthalmic solution (n = 76) or a fixed combination of polyethylene glycol 400 0.4 % and propylene glycol 0.3 % (PEG/PG) (n = 72). Subjects self-dosed four times daily during 60 days. Follow-up was set on days 2, 7, 15, 30 and 60. Assessments of anterior/posterior segment ocular signs were performed. The outcome measures included Schirmer test, tear film break-up time and OSDI score. Security variables included intraocular pressure, lisamine green and fluorescein ocular surface stains. RESULTS: The primary efficacy endpoints were similar between groups at baseline. After intervention time Schirmer test increased in both groups compared to baseline, XG/CS (6.4 ± 2.2 vs 11.0 ± 6.6; p = 0.002) and PEG/PG (6.5 ± 2.5 vs 10.5 ± 5.6; p = 0.019) respectively. Similar results were reported in the tear film break-up time in XG/CS (5.5 ± 2.1 vs 7.4 ± 2.9; p = 0.027) and PEG/PG (5.2 ± 2.0 vs 7.4 ± 2.7; p = 0.046) respectively. The OSDI score decreased to normal values in both groups, XG/CS (19.3 ± 7.4 vs 7.3 ± 5.9; p = 0.001) and PEG/PG (19.3 ± 7.5 vs 7.9 ± 8.2; p = 0.001) respectively. There was no significant difference between treatments for any parameter. Moreover, both groups decreased the presence of burning sensation, tearing, foreign body sensation, conjunctival hyperemia and photophobia. The adverse events were not related to the interventions. CONCLUSIONS: Xanthan gum/chondroitin sulfate preservative free showed similar clinical efficacy, evaluated with OSDI score, TBUT and Schirmer test compared to polyethylene glycol/propylene glycol in the treatment of dry eye disease. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01657253 . Date of registration May 19, 2014.

Atypical mycobacterium keratitis associated with penetrating keratoplasty: case report of successful therapy with topical gatifloxacin 0.3%.

PURPOSE: To report successful therapy with gatifloxacin 0.3% ophthalmic solution (Zymar) in a patient with atypical mycobacterium keratitis after penetrating keratoplasty. METHODS: A 58-year-old patient was referred for evaluation of microbial keratitis after penetrating keratoplasty. RESULTS: Clinical examination of the patient revealed an infiltrate at the inferior graft-host junction with a satellite lesion with a mild inflammatory reaction in the anterior chamber. Microbiologic evaluation confirmed the diagnosis of atypical mycobacteria keratitis. The corneal abscess was completely eradicated with a topical course of gatifloxacin 0.3% with preservation of graft clarity and good visual acuity. Topical treatment with gatifloxacin 0.3% was continued for an additional period of 5 months. CONCLUSION: Topical gatifloxacin 0.3% may be successfully used to treat microbial keratitis resulting from atypical mycobacteria.

Fusarium keratitis in Mexico.

PURPOSE: To describe the clinical characteristics, diagnosis, treatment, and visual outcome of 61 cases of Fusarium keratitis in Mexico. METHODS: Retrospective, comparative study of 61 patients with clinically and culture-confirmed Fusarium keratitis, who were attended at an eye hospital in Mexico City from 1981 to 2001. RESULTS: Fusarium solani was the main causal agent in 83.6% of cases. Trauma history was observed in 57.4% and a history of agricultural activity in 34.4%. Signs were redness (100%), epithelial defects (98.3%), superficial corneal ulcer (95.1%), anterior chamber inflammation (91.8%), and satellite infiltrates (75.4%). In 50% of cases, the treatment was topical ketoconazole 2%; in 34.2% of cases, additional topical antifungal preparations were used. A total of 77% of patients improved and 23% worsened. Conjunctival flap was indicated in 4 of 61 patients (6.5%), and 14 of 61 patients (23%) underwent penetrating keratoplasty. Two of 61 patients were treated with tectonic keratoplasty. Evisceration surgeries were practiced in 14 of 61 patients (22.9%). The final visual acuity after medical or medical/surgical therapy, was no light perception (NLP) in 19 patients (33.33%), light perception (LP) to hand movements (HM) in 18 patients (31.57%), 20/400 to 20/200 in 1 patient (1.75%), 20/150 to 20/60 in 5 patients (8.77%), and 20/40 to 20/20 in 14 patients (24.56%). Four patients were lost to follow-up. CONCLUSIONS: Fusarium is the most common cause of fungal keratitis in Mexico. Most cases (43/54, 79.6%) improved with topical antifungal therapy (either monotherapy or combined). We suggest surgical therapy with conjunctival flap or penetrating keratoplasty in advanced cases, when there has been poor response to medical therapy or a very low final visual acuity.

Degeneración corneal marginal de Terrien. Presentación de un caso y revisión de la literatura / Terrien's marginal degeneration. Case and literature report

La degeneración corneal marginal de Terrien es un raro adelgazamiento corneal periférico. La descripción clásica es la de un adelgazamiento corneal progresivo que comienza superiormente con una excavación periférico presentando un infiltrado lípido en su borde central y vascularizado en su base; el epitelio que lo recubre está siempre intacto. La enfermedad es generalmente bilateral, pero puede ser asimétrica, ocurre predominantemente en pacientes de edad media y no está asociada a inflamación. Presentamos un caso de la enfermedad que inició en 1987 cuando la paciente tenía 8 años de edad y ha permanecido en observación hasta el presente