Monocyte (THP-1) Response to Silver Nanoparticles Synthesized with Rumex hymenosepalus Root Extract.

The study, synthesis, and application of nanomaterials in medicine have grown exponentially in recent years. An example of this is the understanding of how nanomaterials activate or regulate the immune system, particularly macrophages. In this work, nanoparticles were synthesized using Rumex hymenosepalus as a reducing agent (AgRhNPs). According to thermogravimetric analysis, the metal content of nanoparticles is 55.5% by weight. The size of the particles ranges from 5-26 nm, with an average of 11 nm, and they possess an fcc crystalline structure. The presence of extract molecules on the nanomaterial was confirmed by UV-Vis and FTIR. It was found by UPLC-qTOF that the most abundant compounds in Rh extract are flavonols, flavones, isoflavones, chalcones, and anthocyanidins. The viability and apoptosis of the THP-1 cell line were evaluated for AgRhNPs, commercial nanoparticles (AgCNPs), and Rh extract. The results indicate a minimal cytotoxic and apoptotic effect at a concentration of 12.5 µg/mL for both nanoparticles and 25 µg/mL for Rh extract. The interaction of the THP-1 cell line and treatments was used to evaluate the polarization of monocyte subsets in conjunction with an evaluation of CCR2, Tie-2, and Arg-1 expression. The AgRhNPs nanoparticles and Rh extract neither exhibited cytotoxicity in the THP-1 monocyte cell line. Additionally, the treatments mentioned above exhibited anti-inflammatory effects by maintaining the classical monocyte phenotype CD14++CD16, reducing pro-inflammatory interleukin IL-6 production, and increasing IL-4 production.

Use of psychological interventions among healthcare workers over the 2-year period following the COVID-19 pandemic: A longitudinal study.

INTRODUCTION: Although healthcare workers (HCWs) have reported mental health problems since the beginning of the COVID-19 pandemic, they rarely use psychological support. Here, we described the use of psychological support among HCWs in Spain over the 2-year period following the initial pandemic outbreak and explore its association with workplace- and COVID-19-related factors measured at baseline, in 2020. MATERIALS AND METHODS: We conducted a longitudinal study on HCWs working in Spain. We used an online survey to collect information on sociodemographic characteristics, depressive symptoms, workplace- and COVID-19-related variables, and the use of psychological support at three time points (2020, 2021, and 2022). Data was available for 296, 294, and 251 respondents, respectively at time points 1, 2, and 3. RESULTS: Participants had a median age of 43 years and were mostly females (n = 242, 82%). The percentage of HCWs using psychological support increased from 15% in 2020 to 23% in 2022. Roughly one in four HCWs who did not use psychological support reported symptoms compatible with major depressive disorder at follow up. Baseline predictors of psychological support were having to make decisions about patients' prioritisation (OR 5.59, 95% CI 2.47, 12.63) and probable depression (wave 2: OR 1.12, 95% CI 1.06, 1.19; wave 3: OR 1.10, 95% CI 1.04, 1.16). CONCLUSIONS: Our results suggest that there is call for implementing mental health promotion and prevention strategies at the workplace, along with actions to reduce barriers for accessing psychological support.

Acute Abortive Therapies for Seizure Clusters in Long-Term Care.

OBJECTIVES: To describe acute seizure treatment for the long-term care setting, emphasizing rescue (acute abortive) medications for on-site management of acute unexpected seizures and seizure clusters. DESIGN: Narrative review. SETTING AND PARTICIPANTS: People with seizures in long-term care, including group residences. METHODS: PubMed was searched using keywords that pertained to rescue medications, seizure emergencies/epilepsy, seizure action plans, and long-term care. RESULTS: Seizure disorder, including epilepsy, is prevalent in long-term care residences, and rescue medications can be used for on-site treatment. Diazepam rectal gel, intranasal midazolam, and diazepam nasal spray are US Food and Drug Administration (FDA)-approved seizure-cluster rescue medications, and intravenous diazepam and lorazepam are approved for status epilepticus. Benzodiazepines differ by formulation, route of administration, absorption, and metabolism. Intranasal formulations are easy and ideal for public use and when rectal treatment is challenging (eg, wheelchair). Intranasal, intrabuccal, and rectal formulations do not require specialized training to administer and are easier for staff at all levels of training compared with intravenous treatment. Off-label rescue medications may have anecdotal support; however, potential disadvantages include variable absorption and onset of action as well as potential risks to patients and caregivers or care partners. Delivery of intravenous-administered rescue medications is delayed by the time needed to set up and deliver the medication and is subject to dosing errors. Seizure action plans that include management of acute seizures can optimize the quality and timing of treatment, which may reduce emergency service needs and prevent progression to status epilepticus. CONCLUSIONS AND IMPLICATIONS: Seizure disorder is prevalent across all ages but is increased in older adults and in those with intellectual and developmental disabilities. Prompt intervention may reduce negative outcomes associated with acute unexpected seizures and seizure clusters. Seizure action plans that include acute seizures can improve the treatment response by detailing the necessary information for staff to provide immediate treatment.

Lethality risk markers by sex and age-group for COVID-19 in Mexico: a cross-sectional study based on machine learning approach.

BACKGROUND: Mexico ranks fifth worldwide in the number of deaths due to COVID-19. Identifying risk markers through easily accessible clinical data could help in the initial triage of COVID-19 patients and anticipate a fatal outcome, especially in the most socioeconomically disadvantaged regions. This study aims to identify markers that increase lethality risk in patients diagnosed with COVID-19, based on machine learning (ML) methods. Markers were differentiated by sex and age-group. METHODS: A total of 11,564 cases of COVID-19 in Mexico were extracted from the Epidemiological Surveillance System for Viral Respiratory Disease. Four ML classification methods were trained to predict lethality, and an interpretability approach was used to identify those markers. RESULTS: Models based on Extreme Gradient Boosting (XGBoost) yielded the best performance in a test set. This model achieved a sensitivity of 0.91, a specificity of 0.69, a positive predictive value of 0.344, and a negative predictive value of 0.965. For female patients, the leading markers are diabetes and arthralgia. For males, the main markers are chronic kidney disease (CKD) and chest pain. Dyspnea, hypertension, and polypnea increased the risk of death in both sexes. CONCLUSIONS: ML-based models using an interpretability approach successfully identified risk markers for lethality by sex and age. Our results indicate that age is the strongest demographic factor for a fatal outcome, while all other markers were consistent with previous clinical trials conducted in a Mexican population. The markers identified here could be used as an initial triage, especially in geographic areas with limited resources.

The ctpF Gene Encoding a Calcium P-Type ATPase of the Plasma Membrane Contributes to Full Virulence of Mycobacterium tuberculosis.

Identification of alternative attenuation targets of Mycobacterium tuberculosis (Mtb) is pivotal for designing new candidates for live attenuated anti-tuberculosis (TB) vaccines. In this context, the CtpF P-type ATPase of Mtb is an interesting target; specifically, this plasma membrane enzyme is involved in calcium transporting and response to oxidative stress. We found that a mutant of MtbH37Rv lacking ctpF expression (MtbΔctpF) displayed impaired proliferation in mouse alveolar macrophages (MH-S) during in vitro infection. Further, the levels of tumor necrosis factor and interferon-gamma in MH-S cells infected with MtbΔctpF were similar to those of cells infected with the parental strain, suggesting preservation of the immunogenic capacity. In addition, BALB/c mice infected with Mtb∆ctpF showed median survival times of 84 days, while mice infected with MtbH37Rv survived 59 days, suggesting reduced virulence of the mutant strain. Interestingly, the expression levels of ctpF in a mouse model of latent TB were significantly higher than in a mouse model of progressive TB, indicating that ctpF is involved in Mtb persistence in the dormancy state. Finally, the possibility of complementary mechanisms that counteract deficiencies in Ca2+ transport mediated by P-type ATPases is suggested. Altogether, our results demonstrate that CtpF could be a potential target for Mtb attenuation.

Lack of clinically relevant differences in safety and pharmacokinetics after second-dose administration of intranasal diazepam within 4 h for acute treatment of seizure clusters: A population analysis.

OBJECTIVE: Current diazepam nasal spray labeling requires waiting 4 h before administering a second dose. The objective of the current analyses was to examine safety and pharmacokinetic profiles of second doses of diazepam nasal spray given 0-4 h after the first dose. METHODS: Two datasets were analyzed. The first, a long-term, repeat-dose safety study of diazepam nasal spray, compared rates of treatment-emergent adverse events (TEAEs), serious TEAEs, and treatment-related TEAEs for patients receiving ≥1 second dose ≤4 h versus all second doses >4 h after the first. The second was a population pharmacokinetic analysis using data from three phase 1 studies to model drug exposure when a second dose of diazepam nasal spray was administered across multiple time points (1 min-4 h) following the first dose. RESULTS: In the repeat-dose safety study, a second dose of diazepam nasal spray was administered ≤24 h after the first to treat 485 seizure clusters in 79 patients. Rates of TEAEs were similar between patients receiving ≥1 second dose in ≤4 h (89.5%, n = 38) compared with >4-24 h only (80.5%, n = 41). The most common treatment-related TEAEs were associated with nasal discomfort, which was mild or moderate and transient. There were no reports of respiratory or cardiac depression. The pharmacokinetic simulations of second doses predicted comparable elevations of plasma diazepam concentrations with administrations across a range of intervals after the first dose (1 min-4 h). SIGNIFICANCE: These data indicate that the safety and pharmacokinetic profiles of a second dose of diazepam nasal spray administered within 4 h of the first dose are consistent with those associated with current labeling. This is potentially important for patients with seizure clusters who have a recurrent seizure within 4 h of first treatment and might benefit from immediate retreatment to reduce the risk of progression to status epilepticus.

Bilateral vocal fold paralysis after COVID-19 infection. Another neuro-invasive manifestation? Case series / Parálisis bilateral de cuerdas vocales tras infección por COVID-19. ¿Una manifestación neuroinvasiva? Serie de casos

Abstract The agent that causes the coronavirus disease (COVID-19), associated with the severe acute respiratory syndrome (SARS-CoV-2), produces a spectrum of symptoms that mainly affect the respiratory system, the central nervous system (CNS), the regulation of hemostasis and the immune system. Bilateral vocal fold paralysis (BVFP) is a condition of unknown incidence among infected patients, either because it is short-lived or because of the difficulty in establishing a direct cause to the virus. Viral infection has been described in the literature as a cause of BVFP and there is the suspicion that a proportion of the idiopathic cases are due to undiagnosed viral infections. Although the neurotropic mechanisms for SARS-CoV-2 remain unclear, there is strong evidence to ensure its neuroinvasive potential. The most frequent etiologies of BVFP are trauma, neoplasm, and neurological, but a viral origin should not be ruled out. Causality between COVID-19 and BVFP is plausible and will require further study in the short and long term. We present a case series that support and discuss the hypothesis under consideration.

Resumen El agente causal de la enfermedad por coronavirus (COVID-19), asociado a síndrome respiratorio agudo grave (SARS-CoV-2), genera un espectro de síntomas que afectan fundamentalmente el sistema respiratorio, el sistema nervioso central (SNC), la regulación hemostásica y el sistema inmune. La parálisis bilateral de cuerdas vocales (PBCV) es una entidad cuya incidencia en infectados se desconoce, bien porque no se presentan durante el tiempo suficiente o por la dificultad de establecer una causalidad directa con el virus. La infección vírica, como causa de PBCV, está descrita en la literatura y se sospecha que una parte de los casos idiopáticos corresponden a infecciones víricas no diagnosticadas. Aunque los mecanismos neurotrópicos no están completamente aclarados para el SARS-CoV-2, existen indicios sólidos para asegurar su potencial neuroinvasivo. Las causas traumáticas, neoplásicas y neurológicas son las etiologías más comunes de PBCV, sin que se pueda descartar el origen vírico. Es plausible una causalidad entre el COVID-19 y la PBCV, que requerirá mayores estudios a corto y largo plazo. Presentamos una serie de casos que sostienen y discuten la hipótesis en consideración.

Final results from a Phase 3, long-term, open-label, repeat-dose safety study of diazepam nasal spray for seizure clusters in patients with epilepsy.

OBJECTIVE: A Phase 3 open-label safety study (NCT02721069) evaluated long-term safety of diazepam nasal spray (Valtoco) in patients with epilepsy and frequent seizure clusters. METHODS: Patients were 6-65 years old with diagnosed epilepsy and seizure clusters despite stable antiseizure medications. The treatment period was 12 months, with study visits at Day 30 and every 60 days thereafter, after which patients could elect to continue. Doses were based on age and weight. Seizure and treatment information was recorded in diaries. Treatment-emergent adverse events (TEAEs), nasal irritation, and olfactory changes were recorded. RESULTS: Of 163 patients in the safety population, 117 (71.8%) completed the study. Duration of exposure was ≥12 months for 81.6% of patients. There was one death (sudden unexpected death in epilepsy) and one withdrawal owing to a TEAE (major depression), both considered unlikely to be related to treatment. Diazepam nasal spray was administered 4390 times for 3853 seizure clusters, with 485 clusters treated with a second dose within 24 h; 53.4% of patients had monthly average usage of one to two doses, 41.7% two to five doses, and 4.9% more than five doses. No serious TEAEs were considered to be treatment related. TEAEs possibly or probably related to treatment (n = 30) were most commonly nasal discomfort (6.1%); headache (2.5%); and dysgeusia, epistaxis, and somnolence (1.8% each). Only 13 patients (7.9%) showed nasal irritation, and there were no relevant olfactory changes. The safety profile of diazepam nasal spray was generally similar across subgroups based on age, monthly usage, concomitant benzodiazepine therapy, or seasonal allergy/rhinitis. SIGNIFICANCE: In this large open-label safety study, the safety profile of diazepam nasal spray was consistent with the established profile of rectal diazepam, and the high retention rate supports effectiveness in this population. A second dose was used in only 12.6% of seizure clusters.

Au@Ag Core@Shell Nanoparticles Synthesized with Rumex hymenosepalus as Antimicrobial Agent.

In this work, we used a sequential method of synthesis for gold-silver bimetallic nanoparticles with core@shell structure (Au@AgNPs). Rumex hymenosepalus root extract (Rh), which presents high content in catechins and stilbenes, was used as reductor agent in nanoparticles synthesis. Size distribution obtained by Transmission Electron Microscopy (TEM) gives a mean diameter of 36 ± 11 nm for Au@AgNPs, 24 ± 4 nm for gold nanoparticles (AuNPs), and 13 ± 3 nm for silver nanoparticles (AgNPs). The geometrical shapes of NPs were principally quasi-spherical. The thickness of the silver shell over AuNPs is around 6 nm and covered by active biomolecules onto the surface. Nanoparticles characterization included high angle annular dark field images (HAADF) recorded with a scanning transmission electron microscope (STEM), Energy-Dispersive X-ray Spectroscopy (EDS), X-Ray Diffraction (XRD), UV-Vis Spectroscopy, Zeta Potential, and Dynamic Light Scattering (DLS). Fourier Transform Infrared Spectrometer (FTIR), and X-ray Photoelectron Spectroscopy (XPS) show that nanoparticles are stabilized by extract molecules. A growth kinetics study was performed using the Gompertz model for microorganisms exposed to nanomaterials. The results indicate that AgNPs and Au@AgNPs affect the lag phase and growth rate of Escherichia coli and Candida albicans in a dose-dependent manner, with a better response for Au@AgNPs.

Telephone-based depression self-management in Hispanic adults with epilepsy: a pilot randomized controlled trial.

Depression is associated with adverse outcomes in epilepsy but is undertreated in this population. Project UPLIFT, a telephone-based depression self-management program, was developed for adults with epilepsy and has been shown to reduce depressive symptoms in English-speaking patients. There remains an unmet need for accessible mental health programs for Hispanic adults with epilepsy. The purpose of this study was to evaluate the feasibility, acceptability, and effects on depressive symptoms of a culturally adapted version of UPLIFT for the Hispanic community. Hispanic patients with elevated depressive symptoms (n = 72) were enrolled from epilepsy clinics in New York City and randomized to UPLIFT or usual care. UPLIFT was delivered in English or Spanish to small groups in eight weekly telephone sessions. Feasibility was assessed by recruitment, retention, and adherence rates and acceptability was assessed by self-reported satisfaction with the intervention. Depressive symptoms (PHQ-9 scores) were compared between study arms over 12 months. The mean age was 43.3±11.3, 71% of participants were female and 67% were primary Spanish speakers. Recruitment (76% consent rate) and retention rates (86-93%) were high. UPLIFT participants completed a median of six out of eight sessions and satisfaction ratings were high, but rates of long-term practice were low. Rates of clinically significant depressive symptoms (PHQ-9 ≥5) were lower in UPLIFT versus usual care throughout follow-up (63% vs. 72%, 8 weeks; 40% vs. 70%, 6 months; 47% vs. 70%, 12 months). Multivariable-adjusted regressions demonstrated statistically significant differences at 6 months (OR = 0.24, 95% CI, 0.06-0.93), which were slightly reduced at 12 months (OR = 0.30, 95% CI, 0.08-1.16). Results suggest that UPLIFT is feasible and acceptable among Hispanic adults with epilepsy and demonstrate promising effects on depressive symptoms. Larger trials in geographically diverse samples are warranted.

Consistent safety and tolerability of Valtoco® (diazepam nasal spray) in relationship to usage frequency in patients with seizure clusters: Interim results from a phase 3, long-term, open-label, repeat-dose safety study.

OBJECTIVE: Need for rescue therapy differs among patients with seizure clusters. Diazepam nasal spray is approved to treat seizure clusters in patients with epilepsy ≥6 years of age. This analysis used interim data from a phase 3 safety study to assess safety profile and effectiveness of diazepam nasal spray using average number of doses/month as a proxy measurement. METHODS: This phase 3, open-label, repeat-dose, safety study of diazepam nasal spray enrolled patients (6-65 years) with epilepsy and need of benzodiazepine rescue. Patients were stratified by average number of doses/month (<2, moderate frequency; 2-5, high frequency; >5, very-high frequency). Safety was evaluated based on treatment-emergent adverse events (TEAEs), assessed nasal irritation, and olfaction. The proportion of treatments given as a second dose was used as an exploratory proxy for effectiveness. RESULTS: Of 175 enrolled patients (data cutoff, October 31, 2019), 158 received ≥1 dose of diazepam nasal spray. Frequency of use was moderate in 43.7% of patients, high in 50.6% of patients, and very high in 5.7% of patients. Patients treated 3397 seizure episodes (moderate frequency, 14.2%; high frequency, 59.9%; very high frequency, 25.8%). Nasal discomfort was the most common treatment-related TEAE in all groups. No notable changes in nasal irritation or olfaction were observed. Second doses represented only 2.5%, 7.5%, and 17.2% of all doses in the moderate-, high-, and very-high-frequency groups, respectively. Overall retention rate was 82.9%, without an observed relationship to frequency of use. SIGNIFICANCE: Frequency of dosing diazepam nasal spray had little impact on the safety/tolerability profile across a range of <2 to >5 doses/month. Effectiveness was suggested for all dosing frequencies by the high proportion of seizure clusters not treated with a second dose. These results support the utility, safety profile, and effectiveness of diazepam nasal spray across frequencies of seizure cluster burden.

Evaluation of diazepam nasal spray in patients with epilepsy concomitantly using maintenance benzodiazepines: An interim subgroup analysis from a phase 3, long-term, open-label safety study.

OBJECTIVE: Diazepam nasal spray (Valtoco), indicated for acute treatment of frequent seizure activity (seizure clusters) in patients with epilepsy ≥6 years of age, is designed to be a rapid, noninvasive, socially acceptable route of administration. This interim analysis evaluated the safety profile of diazepam nasal spray in patients with and without concomitant use of benzodiazepines, with use of a second dose for a seizure cluster as a proxy for effectiveness. METHODS: A long-term, phase 3, open-label safety study enrolled patients with epilepsy who had seizures despite a stable antiseizure medication regimen. RESULTS: Among 175 patients enrolled by October 31, 2019, a total of 158 were treated with diazepam nasal spray (aged 6-65 years; 53.8% female). Of those, 119 (75.3%) received concomitant benzodiazepines (60, chronic; 59, intermittent); 39 (24.7%) did not. Use of a second dose was similar in patients using chronic concomitant benzodiazepines (second dose in 11.1% [144/1299]) and those with no concomitant benzodiazepines (second dose in 10.3% [41/398]). Treatment emergent adverse events (TEAEs) occurred for 80.0% with chronic use of concomitant benzodiazepines and 61.5% without. Cardiorespiratory depression was not reported, and no serious TEAEs were treatment related. Study retention was high: 83.3% in the chronic benzodiazepine group and 76.9% in the no-benzodiazepine group. Findings were similar in a sub-analysis of patients who were (n = 44) or were not (n = 75) taking clobazam. SIGNIFICANCE: This analysis of patients from a long-term study shows a similar safety profile of diazepam nasal spray in patients with and without concomitant benzodiazepines, and consistent with the established profile for diazepam. Use of a single dose of diazepam nasal spray and high study retention rates suggest the effectiveness of diazepam nasal spray in patients irrespective of chronic daily benzodiazepine use. Results were similar in the clobazam sub-analysis. These results support the safety and effectiveness of diazepam nasal spray in patients with concomitant benzodiazepine use.

Perampanel and pregnancy.

OBJECTIVE: The objective was to summarize pregnancy and fetal/postnatal outcomes following maternal perampanel exposure using preclinical and clinical data, and to use physiologically based pharmacokinetic (PBPK) modeling to improve understanding of perampanel pharmacokinetics (PK) during pregnancy. METHODS: Preclinical developmental studies with perampanel were conducted in pregnant rats and rabbits. Clinical data were collated from the Eisai global perampanel safety database, comprising reports of perampanel exposure during pregnancy from routine clinical settings, interventional studies, and non-interventional post-marketing studies, searched for events coded to Medical Dictionary for Regulatory Activities (MedDRA) high-level group terms of Pregnancy, Labor, Delivery, and Postpartum Conditions and/or the Standardized MedDRA Query terms of Congenital, Familiar, and Genetic Disorders. A PBPK model was used to predict clinical perampanel PK throughout pregnancy. RESULTS: Preclinical studies indicated that perampanel may be linked with post-implantation loss and/or some specific physical development delays but not fertility and early embryonic development. As of August 31, 2018, 96 pregnancies in 90 women receiving perampanel had been reported. No concomitant medications were reported in 26 (28.9%) women taking perampanel. Overall, 43 pregnancies reached full term (all normal live births), 28 did not reach term (induced abortion, n = 18; spontaneous miscarriage, n = 6; incomplete spontaneous miscarriage, n = 2; premature delivery, n = 1; stillbirth [Fallot's tetralogy], n = 1), 18 were lost to follow-up, and seven were ongoing at data cut-off. Adverse events were reported in five full-term neonates (low Apgar score, n = 2; fatal neonatal aspiration, n = 1; cystic fibrosis and congenital deafness, n = 1; poor sucking reflex and shallow breathing, n = 1). PK simulations predicted perampanel exposure decreases throughout pregnancy and is up to four- and three-fold lower towards the end of pregnancy compared with non-pregnant women for total and unbound perampanel, respectively. SIGNIFICANCE: These data provide preliminary information on perampanel use during pregnancy and should be interpreted with caution. Further outcome data are required to estimate the prevalence of adverse pregnancy outcomes with perampanel exposure.

Lack of observed impact of history or concomitant treatment of seasonal allergies or rhinitis on repeated doses of diazepam nasal spray administered per seizure episode in a day, safety, and tolerability: Interim results from a phase 3, open-label, 12-month repeat-dose safety study.

Intranasal formulations are commonly used for drug delivery, and the literature has shown that seasonal allergies do not affect nasal administration of some agents. Diazepam nasal spray (Valtoco®) is a proprietary intranasal formulation with n-dodecyl-beta-d-maltoside (Intravail® A3) that is indicated for acute treatment of seizure clusters in patients with epilepsy aged 6 years and older. The analysis presented here is from an interim cutoff of a phase 3 open-label study evaluating the safety and tolerability of diazepam nasal spray. This analysis assessed whether seasonal allergies alter control of seizures with an intranasal formulation, using administration of a second dose as a surrogate efficacy endpoint. Of 158 evaluated patients with epilepsy having seizures despite a stable anti-seizure regimen, 62 patients had medical histories that included seasonal allergies or rhinitis. The results of this analysis show that seasonal allergies did not appear to influence use of a second dose; the groups of patients with and without a history of seasonal allergies both presented with low rates of seizure episodes for which a second dose was used, which suggests that there is not a major difference in pattern of use. Diazepam nasal spray demonstrated a similar safety and tolerability profile in patients with and without a history of seasonal allergies.

Upper Limb Lengthening in Achondroplasia Using Unilateral External Fixation.

PURPOSE: The purpose of this study was to analyze the long-term results of humeral lengthening in achondroplastic patients and make suggestions on the most appropriate surgical technique to improve patient outcomes. METHODS: Fifty-four humeral lengthening procedures performed in 27 achondroplastic patients were reviewed. Elongations were performed by means of callotasis with unilateral external fixation. Inclusion criteria were: achondroplastic patients under 17 years without prior arm operations and minimum follow-up of 36 months. RESULTS: Fifty humeri in 25 patients (13 men and 12 women), aged between 9 and 17 years, met the inclusion criteria. Mean humeral lengthening was 8.82 cm (range: 5 to 10.5 cm), which represented an elongation of 54.80% (range: 46% to 63%) of the original length. The healing index was 0.91 months (range: 0.72 to 1.4 mo) per centimeter gained. Shoulder and elbow range of motion and stability were preserved in 47 limbs. Noncomplicated cases consistently experienced a significant functional improvement in the performance of activities of daily living such as putting on footwear and personal hygiene. Short-term complications included 11 pin-tract infections, 1 radial nerve neuropraxia, and 1 failure of the regenerated bone formation. None of these complications prevented from completion of treatment. Long-term complications included 2 cases of nonunion, 3 elbow flexion contractures, and 2 cases of psychological dissatisfaction, all of them in 4 patients. Factors associated with long-term complications were intraoperative fragment displacement and distal humeral osteotomy. No fractures of the regenerated bone were identified in the long term. CONCLUSIONS: Callotasis with unilateral external fixation is a reliable and well-tolerated procedure for humeral lengthening in achondroplastic patients, with an acceptable complication rate. Guided fixator placement and a proximal humeral osteotomy are strongly recommended technical tips as they may help prevent complications and improve outcomes. LEVEL OF EVIDENCE: Level IV-case series.

Keeping the team together: Transformation of an inpatient neurology service at an urban, multi-ethnic, safety net hospital in New York City during COVID-19.

The COVID-19 pandemic dramatically affected the operations of New York City hospitals during March and April of 2020. This article describes the transformation of a neurology division at a 450-bed tertiary care hospital in a multi-ethnic community in Brooklyn during this initial wave of COVID-19. In lieu of a mass redeployment of staff to internal medicine teams, we report a novel method for a neurology division to participate in a hospital's expansion of care for patients with COVID-19 while maintaining existing team structures and their inherent supervisory and interpersonal support mechanisms.

Prevalence of clinical and radiological osteoarthritis in knee, hip, and hand in an urban adult population of Mexico City.

INTRODUCTION: Osteoarthritis (OA) is the most prevalent articular disease worldwide, and its prevalence is highly variable depending on the classification criteria, population studied, and/or affected joints considered. Reporting epidemiologic data about clinical and radiological OA prevalence in Mexico has not been done before. PATIENTS AND METHODS: A descriptive cross-sectional study was carried out with participants of Mexico City, and included both men and women above 40 years of age. All participants were evaluated with radiological and clinical criteria for OA. RESULTS: Two hundred and four individuals participated in the study: 80 men (39.2%) and 124 women (60.8%). The average age was 57.4±10.9 years. Using clinical criteria alone, 36 participants were found to have hand OA (17.6%; 95% CI, 13-23.4), 37 with hip OA (18.1%; 95% CI 13.4-24), and 40 with knee OA (19.6%; 95% CI 14.7-25.6). When radiological criteria were used, 51 individuals were reported as having hand OA (25%; 95% CI 19.5-31), 54 with hip OA (26.5%; 95% CI 20.8-32.9), and 52 with knee OA (25.5%; 95% CI 20-31.8). When clinical criteria were used and then corroborated with radiological criteria, the prevalence was 28 individuals with hand OA (13.7%; 95% CI 9.6-19), 31 with hip OA (15.1%; 95% CI 10.9-20.7), and 36 with knee OA 36 (17.6%; 95% CI 12.2-26.2). DISCUSSION: The prevalences found in this study are greater than those found in other studies in Mexico that only report clinical criteria.

Synthesis of Gold Nanoparticles Using Mimosa tenuiflora Extract, Assessments of Cytotoxicity, Cellular Uptake, and Catalysis.

Synthesis of gold nanoparticles (AuNPs) with plant extracts has gained great interest in the field of biomedicine due to its wide variety of health applications. In the present work, AuNPs were synthesized with Mimosa tenuiflora (Mt) bark extract at different metallic precursor concentrations. Mt extract was obtained by mixing the tree bark in ethanol-water. The antioxidant capacity of extract was evaluated using 2,2-diphenyl-1-picrylhydrazyl and total polyphenol assay. AuNPs were characterized by transmission electron microscopy, X-ray diffraction, UV-Vis and Fourier transform infrared spectroscopy, and X-ray photoelectron spectrometry for functional group determination onto their surface. AuMt (colloids formed by AuNPs and molecules of Mt) exhibit multiple shapes with sizes between 20 and 200 nm. AuMt were tested on methylene blue degradation in homogeneous catalysis adding sodium borohydride. The smallest NPs (AuMt1) have a degradation coefficient of 0.008/s and reach 50% degradation in 190s. Cell viability and cytotoxicity were evaluated in human umbilical vein endothelial cells (HUVEC), and a moderate cytotoxic effect at 24 and 48 h was found. However, toxicity does not behave in a dose-dependent manner. Cellular internalization of AuMt on HUVEC cells was analyzed by confocal laser scanning microscopy. For AuMt1, it can be observed that the material is dispersed into the cytoplasm, while in AuMt2, the material is concentrated in the nuclear periphery.

Inhaled alprazolam rapidly suppresses epileptic activity in photosensitive participants.

OBJECTIVE: Treatment options for seizure clusters are limited; the need for easy-to-administer treatments remains. The Staccato system delivers drug deep into the lung via inhalation. In this phase 2a study, we investigated the ability of three different doses of Staccato alprazolam to suppress the electroencephalographic (EEG) photoparoxysmal response (PPR) compared with placebo in participants with photosensitive seizures. METHODS: Adults (18-60 years) with a diagnosis and history of PPR on EEG with or without an epilepsy diagnosis were eligible to participate. Participants received Staccato alprazolam 0.5, 1.0, and 2.0 mg, and Staccato placebo (twice) in random order. Intermittent photic stimulation and clinical assessments were performed at one predose and seven postdose time points. The primary endpoint of the study was the change in standardized photosensitivity range (SPR) in participants receiving each dose of Staccato alprazolam. RESULTS: Fifteen participants with a prior epilepsy diagnosis were screened; five were enrolled, randomized, and completed the study. All participants were white females with a mean (SD) age of 27.2 (6.8) years. All doses of Staccato alprazolam reduced the SPR at 2 minutes; the effect was sustained through 4 hours for the 0.5-mg dose and 6 hours for the 1.0- and 2.0-mg doses. The magnitude and duration of sedation and sleepiness were dose-related. Four participants (80%) experienced ≥1 adverse event (AE); none was severe or serious. Cough, diarrhea, dysgeusia, oral dysesthesia, sedation, and somnolence were experienced by two participants (40%) each. SIGNIFICANCE: This proof-of-concept study demonstrated that Staccato alprazolam 0.5, 1.0, and 2.0 mg rapidly suppressed epileptiform activity in photosensitive participants with epilepsy. The AE profile of Staccato alprazolam was similar to what has been reported for alprazolam for other indications. The results support further development of Staccato alprazolam as a rescue medication for the acute treatment of seizures.

Photosensitive epilepsy: Robust clinical efficacy of a selective GABA potentiator.

OBJECTIVE: The objective of this phase 2a study was to assess the activity of PF-06372865, a positive allosteric modulator (PAM) of α2/3/5 subunit-containing GABAA receptors with minimal activity at α1-containing receptors, which are believed to mediate many of the adverse events associated with benzodiazepines, in the epilepsy photosensitivity model as a proof-of-principle of efficacy. METHODS: Seven participants with a photoparoxysmal response to intermittent photic stimulation (IPS) at baseline were randomized in a double-blind, 4-period cross-over study examining single doses of 17.5 and 52.5 mg PF-06372865, 2 mg lorazepam (active control), and placebo. Standardized photosensitivity ranges (SPRs) to IPS were recorded at screening, predose, and 1, 2, 4, and 6 hours postdose. The primary endpoint was the average least squares mean change in the SPR in the participant's most sensitive eye condition, across all time points. RESULTS: Both doses of PF-06372865 produced a marked and statistically significant mean reduction in SPR compared to placebo, which was similar in degree to lorazepam. There was complete suppression of SPR in 6/7 participants following PF-06372865 or lorazepam administration. PF-06372865 was safe and well-tolerated. CONCLUSION: PF-06372865 demonstrated highly robust efficacy. This demonstrates anticonvulsant activity of a novel α2/3/5-subtype selective GABAA PAM in humans. Further study of the antiepileptic properties of PF-06372865 is warranted. CLINICALTRIALSGOV IDENTIFIER: NCT02564029. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for people with a stable photoparoxysmal response to intermittent photic stimulation, PF-06372865 reduces the SPR.