Telemental Health Services Usage and Association with Health Care Utilization and Expenditures Among Vulnerable Medicare Beneficiaries in 2019: A Comparative Study Using Propensity Score Matching.

Background: Telemental health (TMH) offers a promising approach to managing major depressive disorder (MDD). The objective of our work was to evaluate TMH usage among a vulnerable population of MDD Medicare beneficiaries and its association with health care utilization and expenditures. Methods: This cohort study analyzed 2019 Mississippi Medicare fee-for-service data for adult beneficiaries with MDD. Subjects were matched by the use of TMH following 1:1 propensity score matching. Comparisons between TMH and non-TMH cohorts were made on health care utilization and expenditure outcomes, adjusting for provider types postmatching. Results: Among 7,673 identified beneficiaries, 551 used TMH and 7,122 did not. Prematching, TMH cohort showed greater proportions of dual beneficiaries, rural residents, subjects with income below $40,000, those with disability entitlement, and higher Charlson comorbidity index scores, compared to the non-TMH cohort (all p < 0.001). Moreover, the TMH cohort had fewer outpatient visits, but more inpatient admissions, emergency department (ED) visits, and higher medical, pharmacy, and total expenditures (all p < 0.001). Postmatching, TMH was associated with a 25% reduction in outpatient visits (p < 0.001) and a 20% reduction in pharmacy expenditures (p = 0.01), with no significant effect on inpatient admissions, ED visits, medical expenditures, or total expenditures. Conclusions: These results underscore the potential of TMH in enhancing accessible health care services for vulnerable populations and affordable services for Medicare. Our results provide a robust baseline for future policy discussions concerning TMH. Future studies should consider identifying barriers to TMH use among vulnerable populations and ensuring equitable and high-quality patient care.

Telemental Health Use Is Associated With Lower Health Care Spending Among Medicare Beneficiaries With Major Depression.

BACKGROUND: Some policymakers are concerned that expanding telehealth coverage may increase Medicare expenditures. However, there is limited evidence on the association of telehealth use with utilization and spending among Medicare beneficiaries with major depression. OBJECTIVE: To examine the differences in spending and utilization among telemental health users and non-telemental health users with major depression. METHODS: We examined 2014-2019 traditional Medicare claims data for beneficiaries aged ≥50 years with major depression in Texas. Multivariable generalized linear models were used to assess the relationships between telemental health use and Medicare spending and utilization while adjusting for patient demographics and programmatic and clinical factors. RESULTS: In each of the years between 2014 and 2019, an average of 4.6% Medicare beneficiaries with major depression had at least 1 telemental health visit. Compared with beneficiaries without a telemental health visit, those who had a telemental health visit were significantly more likely to be enrolled in Medicaid, be Medicare eligible due to a disability, live in a lower income area or in a rural area, and have a higher comorbidity index. Beneficiaries utilizing telemental health services incurred higher unadjusted Medicare spending than those not receiving telemental health services. However, this difference appeared due to beneficiary and programmatic characteristics rather than telemental health use. Adjusting for model covariates, the telemental health group had lower overall per member per year predicted spending, inpatient admissions, and emergency department visits than non-telemental health users. CONCLUSION: Our findings suggest that telemental health care use may improve access to mental health care without increasing Medicare spending among telemental health users in Texas.

The transcriptional legacy of developmental stochasticity.

Genetic and environmental variation are key contributors during organism development, but the influence of minor perturbations or noise is difficult to assess. This study focuses on the stochastic variation in allele-specific expression that persists through cell divisions in the nine-banded armadillo (Dasypus novemcinctus). We investigated the blood transcriptome of five wild monozygotic quadruplets over time to explore the influence of developmental stochasticity on gene expression. We identify an enduring signal of autosomal allelic variability that distinguishes individuals within a quadruplet despite their genetic similarity. This stochastic allelic variation, akin to X-inactivation but broader, provides insight into non-genetic influences on phenotype. The presence of stochastically canalized allelic signatures represents a novel axis for characterizing organismal variability, complementing traditional approaches based on genetic and environmental factors. We also developed a model to explain the inconsistent penetrance associated with these stochastically canalized allelic expressions. By elucidating mechanisms underlying the persistence of allele-specific expression, we enhance understanding of development's role in shaping organismal diversity.

The Many Hosts of Mycobacteria 9 (MHM9): A conference report.

The Many Hosts of Mycobacteria (MHM) meeting series brings together basic scientists, clinicians and veterinarians to promote robust discussion and dissemination of recent advances in our knowledge of numerous mycobacterial diseases, including human and bovine tuberculosis (TB), nontuberculous mycobacteria (NTM) infection, Hansen's disease (leprosy), Buruli ulcer and Johne's disease. The 9th MHM conference (MHM9) was held in July 2022 at The Ohio State University (OSU) and centered around the theme of "Confounders of Mycobacterial Disease." Confounders can and often do drive the transmission of mycobacterial diseases, as well as impact surveillance and treatment outcomes. Various confounders were presented and discussed at MHM9 including those that originate from the host (comorbidities and coinfections) as well as those arising from the environment (e.g., zoonotic exposures), economic inequality (e.g. healthcare disparities), stigma (a confounder of leprosy and TB for millennia), and historical neglect (a confounder in Native American Nations). This conference report summarizes select talks given at MHM9 highlighting recent research advances, as well as talks regarding the historic and ongoing impact of TB and other infectious diseases on Native American Nations, including those in Southwestern Alaska where the regional TB incidence rate is among the highest in the Western hemisphere.

Economic evaluation and costs of remote patient monitoring for cardiovascular disease in the United States: a systematic review.

BACKGROUND: Remote patient monitoring (RPM) has emerged as a viable and valuable care delivery method to improve chronic disease management. In light of the high prevalence and substantial economic burden of cardiovascular disease (CVD), this systematic review examines the cost and cost-effectiveness of using RPM to manage CVD in the United States. METHODS: We systematically searched databases to identify potentially relevant research. Findings were synthesized for cost and cost-effectiveness by economic study type with consideration of study perspective, intervention, clinical outcome, and time horizon. The methodological quality was assessed using the Joanna Briggs Institute Checklist for Economic Evaluations. RESULTS: Thirteen articles with fourteen studies published between 2011 and 2021 were included in the final review. Studies from the provider perspective with a narrow scope of cost components identified higher costs and similar effectiveness for the RPM group relative to the usual care group. However, studies from payer and healthcare sector perspectives indicate better clinical effectiveness of RPM relative to usual care, with two cost-utility analysis studies suggesting that RPM relative to usual care is a cost-effective tool for CVD management even at the conservative $50,000 per Quality-Adjusted Life-Year threshold. Additionally, all model-based studies revealed that RPM is cost-effective in the long run. CONCLUSIONS: Full economic evaluations identified RPM as a potentially cost-effective tool, particularly for long-term CVD management. In addition to the current literature, rigorous economic analysis with a broader perspective is needed in evaluating the value and economic sustainability of RPM.

Surgically treated pediatric tongue masses: A 20 Year review.

OBJECTIVE: Pediatric tongue lesions represent a rare, diverse group of pathologies related to congenital malformations, inflammatory changes, and neoplastic masses. We present the largest-to-date series of pediatric tongue lesions managed surgically. SETTING: Charts of all pediatric patients with a tongue lesion surgically treated at a regional children's hospital from February 1st, 1997 to August 30th, 2019 were reviewed. METHODS: After obtaining institutional review board approval, a retrospective review was completed of all pediatric patients with a tongue lesion surgically treated at a regional children's hospital from February 1st, 1997 through August 30th, 2019. Charts were evaluated for patient demographics as well as symptoms at presentation, surgical details, pathologic evaluation of the lesion, and rates of recurrence. Categorical variables were compared between various groups using Chi-square and/or Fisher's exact tests. Univariate and multivariable logistic regression analysis was performed unadjusted and adjusted to further explore these relationships. RESULTS: 159 patients were included in the study with ages distributed relatively even across infants (27.7%), children 1-5 years (27.7%), 6-10 years (23.3%), and greater than 10 years of age (21.4%). Patient/family reported race/ethnic background was most commonly Caucasian (34.8%) or Hispanic/Latino/Spanish Origin (34.0%) followed by Black or African American (21.3%). The most commonly reported symptoms were pain (23.3%), difficulty with oral intake (12.6%), bleeding (11.3%), and respiratory distress (11%). Patients with lesions of the base of tongue were significantly more likely to present with respiratory distress or difficulty with oral intake (p < 0.001). The likelihood of recurrence was observed to be higher with lesions managed in infancy (OR 3.85, CI 1.47-10.0, p = 0.005), those greater than 2 cm (OR 3.45, CI 1.34-8.71, p = 0.009), or with laser (OR 4.52, CI 1.25-15.00), p = 0.015). CONCLUSION: Pediatric patients with tongue lesions may present with a wide array of symptoms. Base of tongue lesions should be managed carefully as they are most likely to create barriers to the airway and oral intake. Larger lesions and those managed in infancy are at increased risk for recurrence.

Framework for Evaluating and Developing Sustainable Telehealth Programs.

During the COVID-19 pandemic and public health emergency, telehealth programs vastly expanded with strong support from various federal and state agencies. However, the uncertainty regarding future reimbursement policies for telehealth services has resulted in concerns about long-term sustainability of innovative health service delivery models beyond the financial support. Given the limited literature on creating telehealth programs with long-term sustainability in consideration, we have developed a framework for gathering appropriate data during various stages of program implementation to evaluate clinical effectiveness and economic sustainability that is applicable across various settings, with additional attention to health equity. Recognizing the difficulty of sustaining telehealth programs solely through a fee-for-service payment model, we encourage all telehealth stakeholders, especially payers and policymakers, to consider cost-effectiveness of telehealth programs and support alternate payment models for ensuring long-term sustainability.

Parallel evolution of reduced cancer risk and tumor suppressor duplications in Xenarthra.

The risk of developing cancer is correlated with body size and lifespan within species, but there is no correlation between cancer and either body size or lifespan between species indicating that large, long-lived species have evolved enhanced cancer protection mechanisms. Previously we showed that several large bodied Afrotherian lineages evolved reduced intrinsic cancer risk, particularly elephants and their extinct relatives (Proboscideans), coincident with pervasive duplication of tumor suppressor genes (Vazquez and Lynch, 2021). Unexpectedly, we also found that Xenarthrans (sloths, armadillos, and anteaters) evolved very low intrinsic cancer risk. Here, we show that: (1) several Xenarthran lineages independently evolved large bodies, long lifespans, and reduced intrinsic cancer risk; (2) the reduced cancer risk in the stem lineages of Xenarthra and Pilosa coincided with bursts of tumor suppressor gene duplications; (3) cells from sloths proliferate extremely slowly while Xenarthran cells induce apoptosis at very low doses of DNA damaging agents; and (4) the prevalence of cancer is extremely low Xenarthrans, and cancer is nearly absent from armadillos. These data implicate the duplication of tumor suppressor genes in the evolution of remarkably large body sizes and decreased cancer risk in Xenarthrans and suggest they are a remarkably cancer-resistant group of mammals.

Mycobacterium leprae induces Schwann cell proliferation and migration in a denervated milieu following intracutaneous excision axotomy in nine-banded armadillos.

Nine-banded armadillos develop peripheral neuropathy after experimental Mycobacterium leprae infection that recapitulates human disease. We used an intracutaneous excision axotomy model to assess the effect of infection duration by M. leprae on axonal sprouting and Schwan cell density. 34 armadillos (17 naïve and 17 M. leprae-infected) underwent 3 mm skin biopsies to create an intracutaneous excision axotomy followed by a concentric 4-mm overlapping biopsy 3 and 12-months post M. leprae inoculation. A traditional distal leg biopsy was obtained at 15mo for intraepidermal nerve fiber (IENF) density. Serial skin sections were immunostained against a axons (PGP9.5, GAP43), and Schwann cells (p75, s100) to visualize regenerating nerves. Regenerative axons and proliferation of Schwann cells was measured and the rate of growth at each time point was assessed. Increasing anti-PGL antibody titers and intraneural M. leprae confirmed infection. 15mo following infection, there was evidence of axon loss with reduced distal leg IENF versus naïve armadillos, p < 0.05. This was associated with an increase in Schwann cell density (11,062 ± 2905 vs. 7561 ± 2715 cells/mm3, p < 0.01). Following excisional biopsy epidermal reinnervation increased monotonically at 30, 60 and 90 days; the regeneration rate was highest at 30 days, and decreased at 60 and 90 days. The reinnervation rate was highest among animals infected for 3mo vs those infected for 12mo or naïve animals (mean ± SD, 27.8 ± 7.2 vs.16.2 ± 5.8vs. 15.3 ± 6.5 mm/mm3, p < 0.05). The infected armadillos displayed a sustained Schwann cell proliferation across axotomy time points and duration of infection (3mo:182 ± 26, 12mo: 256 ± 126, naive: 139 ± 49 cells/day, p < 0.05). M. leprae infection is associated with sustained Schwann cell proliferation and distal limb nerve fiber loss. Rates of epidermal reinnervation were highest 3mo after infection and normalized by 12 mo of infection. We postulate that excess Schwann cell proliferation is the main pathogenic process and is deleterious to sensory axons. There is a compensatory initial increase in regeneration rates that may be an attempt to compensate for the injury, but it is not sustained and eventually followed by axon loss. Aberrant Schwann cell proliferation may be a novel therapeutic target to interrupt the pathogenic cascade of M. leprae.

Cost of remote patient monitoring for cardiovascular disease: a systematic review protocol.

OBJECTIVE: This review aims to evaluate the costs and cost-effectiveness of remote patient monitoring for cardiovascular disease in the United States. INTRODUCTION: Cardiovascular disease is a leading public health concern in the United States, resulting in a substantial economic burden. Remote patient monitoring has emerged as a viable and valuable care delivery method to improve cardiovascular disease management at home. However, there is limited systematic research of the cost and cost-effectiveness of using remote patient monitoring to manage the disease. INCLUSION CRITERIA: This review will consider all studies evaluating the cost of remote patient monitoring for cardiovascular disease management in the United States. The population of interest includes all individuals with various types of chronic cardiovascular disease in the United States. METHODS: The search strategy will locate both published and unpublished studies. Systematic searches will be completed in PubMed, Embase, Web of Science, CINAHL, Scopus, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, National Health Service Economic Evaluation Database, and the Cost-Effectiveness Analysis Registry. Two reviewers will independently screen titles and abstracts, followed by a full-text review against the inclusion criteria. Disagreements will be resolved through discussion between all study members. The JBI checklist for economic evaluations will be utilized to evaluate the methodological quality of studies. Data will be extracted using a modified version of the JBI data extraction form for economic evaluations. Reviewers will summarize studies and cost-related metrics. The Dominance Ranking Matrix will be used to synthesize full economic evaluation. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42021270621.

Neural correlates of unpredictable Stop and non-Stop cues in overt and imagined execution.

The ability to inhibit incorrect behaviors is crucial for survival. In real contexts, cues that require stopping usually appear intermixed with indications to continue the ongoing action. However, in the classical Stop-signal task (SST), the unpredictable stimuli are always signals that require inhibition. To understand the neural mechanisms activated by low-probability nonstop cues, we recorded the electroencephalography from 23 young volunteers while they performed a modified SST where the unpredictable stimuli could be either Stop or confirmatory Go signals (CGo). To isolate the influence of motor output, the SST was performed during overt and covert execution. We found that, paradoxically, CGo stimuli activated motor inhibition processes, and evoked patterns of brain activity similar to those obtained after Stop signals (N2/P3 event-related potentials and midfrontal theta power increase), though in lesser magnitude. These patterns were also observed during the imagined performance. Finally, applying machine learning procedures, we found that the brain activity evoked after CGo versus Stop signals can be classified above chance during both, overt and imagined execution. Our results provide evidence that unpredictable signals cause motor inhibition even when they require to continue an ongoing action.

Transcranial direct current stimulation of 3 cortical targets is no more effective than placebo as treatment for fibromyalgia: a double-blind sham-controlled clinical trial.

ABSTRACT: Transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) and the dorsolateral prefrontal cortex seem to improve pain and other symptoms of fibromyalgia (FM), although the evidence on the effectiveness of tDCS and the optimal stimulation target is not robust enough. Our main objective was to establish the optimal area of stimulation, comparing the 2 classical targets and a novel pain-related area, the operculo-insular cortex, in a sham-controlled trial. Using a double-blind design, we randomly assigned 130 women with FM to 4 treatment groups (M1, dorsolateral prefrontal cortex, operculo-insular cortex, and sham), each receiving fifteen 20-minute sessions of 2 mA anodal tDCS over the left hemisphere. Our primary outcome was pain intensity. The secondary outcomes were the other core symptoms of FM (fatigue, mood, cognitive and sleep disorders, and hyperalgesia measured by the pressure pain threshold). We performed the assessment at 3 time points (before, immediately after treatment, and at 6 months follow-up). The linear mixed-model analysis of variances showed significant treatment effects across time for clinical pain and for fatigue, cognitive and sleep disturbances, and experimental pain, irrespective of the group. In mood, the 3 active tDCS groups showed a significantly larger improvement in anxiety and depression than sham. Our findings provide evidence of a placebo effect, support the use of tDCS for the treatment of affective symptoms, and challenge the effectiveness of tDCS as treatment of FM.

IL-1R1-Dependent Signals Improve Control of Cytosolic Virulent Mycobacteria In Vivo.

Mycobacterium tuberculosis infections claim more than a million lives each year, and better treatments or vaccines are required. A crucial pathogenicity factor is translocation from phagolysosomes to the cytosol upon phagocytosis by macrophages. Translocation from the phagolysosome to the cytosol is an ESX-1-dependent process, as previously shown in vitro Here, we show that in vivo, mycobacteria also translocate to the cytosol but mainly when host immunity is compromised. We observed only low numbers of cytosolic bacilli in mice, armadillos, zebrafish, and patient material infected with M. tuberculosis, M. marinum, or M. leprae In contrast, when innate or adaptive immunity was compromised, as in severe combined immunodeficiency (SCID) or interleukin-1 receptor 1 (IL-1R1)-deficient mice, significant numbers of cytosolic M. tuberculosis bacilli were detected in the lungs of infected mice. Taken together, in vivo, translocation to the cytosol of M. tuberculosis is controlled by adaptive immune responses as well as IL-1R1-mediated signals.IMPORTANCE For decades, Mycobacterium tuberculosis has been one of the deadliest pathogens known. Despite infecting approximately one-third of the human population, no effective treatment or vaccine is available. A crucial pathogenicity factor is subcellular localization, as M. tuberculosis can translocate from phagolysosome to the cytosol in macrophages. The situation in vivo is more complicated. In this study, we establish that high-level cytosolic escape of mycobacteria can indeed occur in vivo but mainly when host resistance is compromised. The IL-1 pathway is crucial for the control of the number of cytosolic mycobacteria. The establishment that immune signals result in the clearance of cells containing cytosolic mycobacteria connects two important fields, cell biology and immunology, which is vital for the understanding of the pathology of M. tuberculosis.

Effects of the COVID-19 pandemic on chronic pain in Spain: a scoping review.

The COVID-19 outbreak has been a great challenge in the management of chronic pain patients. We have conducted a rapid scoping review to assess the impact of the pandemic (and the associated public health measures) on the health status and management practices of chronic pain patients in Spain. To this end, we performed a bibliographic search in LitCOVID and PubMed, and reviewed official websites and documents, and expert reports. The review showed that (1) the studies consistently indicate that the pandemic has had a very negative impact on the physical and psychological health of chronic pain patients; (2) there are scarce data on how the pandemic affected pain unit consultations and a lack of protocols to organize health care in the face of future waves of contagion, with little implementation of telehealth. We make proposals to improve management of chronic pain patients in pandemic situations, which should pivot around 3 axes: (1) a coordinated response of all the relevant stakeholders to define a future roadmap and research priorities, (2) a biopsychosocial approach in pain management, and (3) development and implementation of novel telemedicine solutions.

Safety and efficacy of unilateral topical application of rocuronium bromide in healthy scops owls (Otus scops).

OBJECTIVE: To evaluate the safety and efficacy of unilateral topical application of rocuronium bromide in scops owls. ANIMALS STUDIED: Ten healthy adult scops owls. PROCEDURES: Birds weighting between 82-111 g were enrolled. Complete physical and ophthalmic examinations were performed. Each animal received a single dose of 0.15 mg of rocuronium bromide (30 µL) in a randomly selected eye. Static pupillometric evaluations were performed before and after drug instillation at 0, 30, 60, 90, and 120 minutes, in a room with fixed light intensity. Physical and ophthalmic examinations were carried out to evaluate possible adverse effects. RESULTS: Median pupil (95% CI) size at t0 was 7.10 mm (5.51-7.41) for placebo eyes and 7.22 mm (6.93-7.48) for treated eyes, showing no statistical differences (P > .05). When compared to the placebo eye, significant mydriasis was achieved at t30 [8.18 mm (7.22-9.00)] (P = .014) and lasting until t90 [7.35 mm (6.20-9.52)] (P = .004). Maximal mydriasis was obtained at t60 [8.63 mm (7.72-9.81)] (P = .001). During this period, the treated eye no longer responded to direct light stimulation. Complete mydriasis was observed in 5/10 birds (mean weight 97.4 g). Pupil size at t90 and t120 did not differ from baseline (P > .05) in treated eyes. No adverse effects were seen during the study period. CONCLUSION: Single-dose topical rocuronium bromide (0.15 mg) is a safe and effective medium duration mydriatic agent in scops owls. Further studies are needed to evaluate bilateral topical application and standardize the mydriatic protocol.

Intracanalicular injection of N-acetylcysteine as adjunctive treatment for sialoceles in dogs: 25 cases (2000-2017).

OBJECTIVE: To describe intracanalicular injection of 10% N-acetylcysteine (IINAC) as adjunctive treatment for sialoceles in dogs. ANIMALS: 25 client-owned dogs. PROCEDURES: Hard copy medical records at 2 veterinary ophthalmology practices were searched to identify dogs that underwent IINAC for treatment of sialoceles from January 2000 to December 2017. Signalment, affected salivary gland, clinical signs, duration of signs, other treatments administered, diagnostic tests performed, anesthetic approach, N-acetylcysteine volume administered, complications, follow-up time, and recurrence of sialoceles were recorded. Descriptive statistics were reported. RESULTS: Boxers and mixed-breed dogs were most commonly represented. Subjectively decreased globe retropulsion and conjunctival or periorbital swelling (23/25 [92%] dogs each) were the most common clinical signs, with no vision deficits in any patient. The zygomatic gland was mainly affected (23/25 [92%] dogs), followed by parotid and mandibular glands (1 [4%] dog each). The condition was unilateral in 22 (88%) dogs. Ultrasonography (19/25 [76%] dogs), MRI (14 [56%]), fine-needle aspiration (20 [80%]), and biopsy (4 [16%]) were performed; however, the condition was deemed idiopathic in 22 (88%) dogs. Most IINACs were performed with local anesthesia (median volume, 5 mL/gland; range, 1.5 to 9 mL). No complications were identified. Other treatments included antimicrobials and anti-inflammatories. Mean follow-up time was 18.8 months. All recurrences (5/23 [22%] dogs) were controlled with medical management. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested noninvasive IINAC may be a useful adjunctive treatment for sialoceles in dogs. The procedure was easily and safely performed with local anesthesia (or general anesthesia with concurrent diagnostic imaging) in these dogs.

Fourteen-year follow-up of a child with acroscyphodysplasia with emphasis on the need for multidisciplinary management: a case report.

BACKGROUND: Acroscyphodysplasia has been described as a phenotypic variant of acrodysostosis type 2 and pseudohypoparathyroidism. In acrodysostosis, skeletal features can include brachydactyly, facial hypoplasia, cone-shaped epiphyses, short stature, and advanced bone age. To date, reports on this disorder have focused on phenotypic findings, endocrine changes, and genetic variation. We present a 14-year overview of a patient, from birth to skeletal maturity, with acroscyphodysplasia, noting the significant orthopaedic challenges and the need for a multidisciplinary team, including specialists in genetics, orthopaedics, endocrinology, and otolaryngology, to optimize long-term outcomes. CASE PRESENTATION: The patient presented as a newborn with dysmorphic facial features, including severe midface hypoplasia, malar flattening, nasal stenosis, and feeding difficulties. Radiologic findings were initially subtle, and a skeletal survey performed at age 7 months was initially considered normal. Genetic evaluation revealed a variant in PDE4D and subsequent pseudohypoparathyroidism. The patient presented to the department of orthopaedics, at age 2 years 9 months with a leg length discrepancy, right knee contracture, and severely crouched gait. Radiographs demonstrated cone-shaped epiphyses of the right distal femur and proximal tibia, but no evidence of growth plate changes in the left leg. The child developed early posterior epiphyseal arrest on the right side and required multiple surgical interventions to achieve neutral extension. Her left distal femur developed late posterior physeal arrest and secondary contracture without evidence of schypho deformity, which improved with anterior screw epiphysiodesis. The child required numerous orthopaedic surgical interventions to achieve full knee extension bilaterally. At age 13 years 11 months, she was an independent ambulator with erect posture. The child underwent numerous otolaryngology procedures and will require significant ongoing care. She has moderate intellectual disability. DISCUSSION AND CONCLUSIONS: Key challenges in the management of this case included the subtle changes on initial skeletal survey and the marked asymmetry of her deformity. While cone-shaped epiphyses are a hallmark of acrodysostosis, posterior tethering/growth arrest of the posterior distal femur has not been previously reported. Correction of the secondary knee contracture was essential to improve ambulation. Children with acroscyphodysplasia require a multidisciplinary approach, including radiology, genetics, orthopaedics, otolaryngology, and endocrinology specialties.

Patients with fibromyalgia show increased beta connectivity across distant networks and microstates alterations in resting-state electroencephalogram.

Fibromyalgia (FM) is a chronic condition characterized by widespread pain of unknown etiology associated with alterations in the central nervous system. Although previous studies demonstrated altered patterns of brain activity during pain processing in patients with FM, alterations in spontaneous brain oscillations, in terms of functional connectivity or microstates, have been barely explored so far. Here we recorded the EEG from 43 patients with FM and 51 healthy controls during open-eyes resting-state. We analyzed the functional connectivity between different brain networks computing the phase lag index after group Independent Component Analysis, and also performed an EEG microstates analysis. Patients with FM showed increased beta band connectivity between different brain networks and alterations in some microstates parameters (specifically lower occurrence and coverage of microstate class C). We speculate that the observed alterations in spontaneous EEG may suggest the dominance of endogenous top-down influences; this could be related to limited processing of novel external events and the deterioration of flexible behavior and cognitive control frequently reported for FM. These findings provide the first evidence of alterations in long-distance phase connectivity and microstate indices at rest, and represent progress towards the understanding of the pathophysiology of fibromyalgia and the identification of novel biomarkers for its diagnosis.

Effects of topical 1% cyclopentolate hydrochloride on quantitative pupillometry measurements, tear production and intraocular pressure in healthy horses.

OBJECTIVE: To evaluate the effect of topical cyclopentolate hydrochloride (CH) on quantitative pupillometric readings (PR), tear production (TP), and intraocular pressure (IOP) in healthy horses. ANIMALS STUDIED: Fourteen client-owned horses. PROCEDURES: In a two-phase design study, each animal received 1% CH ophthalmic solution in the left eye [treated] and 0.9% NaCl in the right eye [control] (0.2 mL each). In the first phase (n = 7), TP, IOP, and PR assessment was performed by Schirmer tear test I, rebound tonometry and static pupillometry, at 1, 8, 24, 48, 72, 96, 120, 148, 172, and 196-hours post-instillation. In the second phase (n = 7), plateau mydriasis was evaluated by assessing PR hourly for 8 hours post-instillation. For PR assessment, pupil area (PA), vertical diameter (VPD), and horizontal diameter (HPD) were recorded. All pupillometries were obtained in a room with fixed light intensity (45-60 lux). Statistical analysis was performed by generalized estimating equations method for the effect on parameters over time. RESULTS: After topical CH, significant differences in pupil dilation were seen from 1 to 172 hours for VPD and from 8 to 24 hours for PA, without significant differences on HPD over time. In the second phase, plateau PA and VPD were reached at 3 hours, while plateau HPD at 2 hours. No significant effects were detected on TP and IOP in both eyes at any time, nor on PR of the nontreated eyes. CONCLUSIONS: Topical 1% cyclopentolate hydrochloride could be considered an effective and safe option when a mydriatic/cycloplegic drug is needed in horses.

Development of LepReact, a defined skin test for paucibacillary leprosy and low-level M. leprae infection.

The persistence of new leprosy cases in endemic areas such as India, Brazil, Bangladesh, and the Philippines has encouraged studies of chemoprophylaxis among contacts of patients. Epidemiological screening tools to enable early detection of infected individuals in endemic populations would be critical to target individuals most in need of intervention. Despite decades of attempts, however, there still are no tests available for the early detection of low-level infection with Mycobacterium leprae. In this report, we describe the development of a leprosy skin test using M. leprae-specific antigens. We selected the chimeric LID-1 fusion protein, formulated to achieve maximum performance at a minimal dose, as a skin test candidate based on its ability to elicit delayed-type hypersensitivity (DTH) reactions in M. leprae immune guinea pigs in a sensitive and specific manner, i.e., with no cross-reactivity observed with other mycobacterial species. Importantly, evaluations in armadillos indicated that intradermal inoculation of formulated LID-1 could distinguish uninfected from M. leprae-infected animals manifesting with symptoms distinctly similar to the PB presentation of patients. Together, our data provide strong proof-of-concept for developing an antigen-specific skin test to detect low-level M. leprae infection. Such a test could, when applied with appropriate use of chemo- and/or immunoprophylaxis, be instrumental in altering the evolution of clinical disease and M. leprae transmission, thus furthering the objective of zero leprosy.