Serious Game with Electromyography Feedback and Physical Therapy in Young Children with Unilateral Spastic Cerebral Palsy and Equinus Gait: A Prospective Open-Label Study.

The clinical effects of a serious game with electromyography feedback (EMGs_SG) and physical therapy (PT) was investigated prospectively in children with unilateral spastic cerebral palsy (USCP). An additional aim was to better understand the influence of muscle shortening on function. Thirty children with USCP (age 7.6 ± 2.1 years) received four weeks of EMGs_SG sessions 2×/week including repetitive, active alternating training of dorsi- and plantar flexors in a seated position. In addition, each child received usual PT treatment ≤ 2×/week, involving plantar flexor stretching and command strengthening on dorsi- and plantar flexors. Five-Step Assessment parameters, including preferred gait velocity (normalized by height); plantar flexor extensibility (XV1); angle of catch (XV3); maximal active ankle dorsiflexion (XA); and derived coefficients of shortening, spasticity, and weakness for both soleus and gastrosoleus complex (GSC) were compared pre and post treatment (t-tests). Correlations were explored between the various coefficients and gait velocities at baseline. After four weeks of EMGs_SG + PT, there was an increase in normalized gait velocity from 0.72 ± 0.13 to 0.77 ± 0.13 m/s (p = 0.025, d = 0.43), a decrease in coefficients of shortening (soleus, 0.10 ± 0.07 pre vs. 0.07 ± 0.08 post, p = 0.004, d = 0.57; GSC 0.16 ± 0.08 vs. 0.13 ± 0.08, p = 0.003, d = 0.58), spasticity (soleus 0.14 ± 0.06 vs. 0.12 ± 0.07, p = 0.02, d = 0.46), and weakness (soleus 0.14 ± 0.07 vs. 0.11 ± 0.07, p = 0.005, d = 0.55). At baseline, normalized gait velocity correlated with the coefficient of GSC shortening (R = -0.43, p = 0.02). Four weeks of EMGs_SG and PT were associated with improved gait velocity and decreased plantar flexor shortening. A randomized controlled trial comparing EMGs_SG and conventional PT is needed.

Factors Affecting Burn Contracture Outcome in Developing Countries: A Review of 2506 Patients.

INTRODUCTION: Burn contractures hinder joint mobility, resulting in functional impairment and reduced quality of life. This is of greater significance in developing countries where there are fewer resources for assistance with such impairments. Contracture release reduces deformity, but multiple factors affect the extent of postsurgical improvements and outcomes. Elucidating these factors may enable surgeons to better care for burn patients. This study assesses factors that impact burn contracture resolution in developing nations. METHODS: A retrospective review of 2506 burn contractures was performed using information extracted from a large nongovernment organization (ReSurge International) database from Nepal, India, and Zambia. Data points included age, type of burn, time elapsed between injury and release, and extent of final release achieved based on preoperative and postoperative images of hand (n = 1960), elbow (n = 371), and knee (n = 176) contractures. Hand improvement was scored based on digit/wrist involvement (severity of dysfunction) and joint extension capability (functionality); elbow and knee improvement were calculated using preoperative and postoperative joint angles. Multivariate analysis was performed. RESULTS: Hands burned by hot liquid had greater functionality after surgery than open-fire burns (P < 0.01). Improvement in severity of dysfunction and functionality were inversely correlated to age (P < 0.01) and time until surgery (P < 0.01). Elbow improvement decreased as age increased (P < 0.01). Postoperative increase of knee extension decreased for each year elapsed between injury and surgery (P < 0.01). CONCLUSIONS: Burn type, age when burned, and timing of surgery were significant factors affecting hand outcomes, whereas age affected elbow outcomes, and time elapsed until surgery affected knee results. An algorithm was formulated to enable physicians in developing countries with limited resources to triage patients and optimize patient outcomes.

Decisions to Choose COVID-19 Vaccination by Health Care Workers in a Southern California Safety Net Medical Center Vary by Sociodemographic Factors.

BACKGROUND: Limited information exists regarding COVID-19 vaccine hesitancy among healthcare workers (HCWs). Our previous survey analyzed the reasons for HCWs' decisions to accept vaccination, suggesting that a "one-size fits all" approach may not suffice to increase vaccine uptake. METHODS: Based on the vaccination acceptance group (acceptor, hesitant, refuser), we examined differences by sociodemographic factors (race/ethnicity, household income, education) from Likert Scale responses to fourteen influences affecting a decision to be vaccinated using the Kruskal-Wallis test and multinomial logistic regression with mutual adjustment for these sociodemographic factors, age, and sex. RESULTS: Non-Hispanic White vaccine acceptors ranked lower confidence in preventing, withstanding, or treating COVID-19, while Non-Hispanic Blacks more highly regarded the motivation of a religious leader, colleague, or family member. Social media was ranked more influential among Non-Hispanic Asians. Acceptors with lower incomes ranked a job requirement influential; conversely, higher income vaccine hesitant HCWs highly rated this reason. More highly educated acceptors ranked being motivated by colleagues, family, and other HCWs higher. Adjustment weakened some but not all the differences between groups. CONCLUSIONS: Sociodemographic factors affect HCWs' decisions to be vaccinated against COVID-19. Our findings may help develop more focused and tailored strategies to improve vaccination acceptance.

Therapeutic utility of natural estrogen receptor beta agonists on ovarian cancer.

Ovarian cancer is the deadliest of all gynecologic cancers. Despite success with initial chemotherapy, the majority of patients relapse with an incurable disease. Development of chemotherapy resistance is a major factor for poor long-term survival in ovarian cancer. The biological effects of estrogens are mediated by estrogen receptor alpha (ERα) and estrogen receptor beta (ERß). Emerging evidence suggests that ovarian cancer cells express ERß that functions as a tumor suppressor; however, the clinical utility of ERß agonists in ovarian cancer remains elusive. We tested the utility of two natural ERß agonists liquiritigenin (Liq), which is isolated from Glycyrrhiza uralensis and S-equol, which is isolated from soy isoflavone daidzein, for treating ovarian cancer. Both natural ERß ligands had significant growth inhibition in cell viability and survival assays, reduced migration and invasion, and promoted apoptosis. Further, ERß agonists showed tumor suppressive functions in therapy-resistant ovarian cancer model cells and sensitized ovarian cancer cells to cisplatin and paclitaxel treatment. Global RNA-Seq analysis revealed that ERß agonists modulate several tumor suppressive pathways, including downregulation of the NF-κB pathway. Immunoprecipitation assays revealed that ERß interacts with p65 subunit of NF-κB and ERß overexpression reduced the expression of NF-κB target genes. In xenograft assays, ERß agonists reduced tumor growth and promoted apoptosis. Collectively, our findings demonstrated that natural ERß agonists have the potential to significantly inhibit ovarian cancer cell growth by anti-inflammatory and pro-apoptotic actions, and natural ERß agonists represent novel therapeutic agents for the management of ovarian cancer.

Selective Estrogen Receptor ß Agonist LY500307 as a Novel Therapeutic Agent for Glioblastoma.

Glioblastomas (GBM), deadly brain tumors, have greater incidence in males than females. Epidemiological evidence supports a tumor suppressive role of estrogen; however, estrogen as a potential therapy for GBM is limited due to safety concerns. Since GBM express ERß, a second receptor for estrogen, targeting ERß with a selective agonist may be a potential novel GBM therapy. In the present study, we examined the therapeutic effect of the selective synthetic ERß agonist LY500307 using in vitro and in vivo GBM models. Treatment with LY500307 significantly reduced the proliferation of GBM cells with no activity on normal astrocytes in vitro. ERß agonists promoted apoptosis of GBM cells, and mechanistic studies using RNA sequencing revealed that LY500307 modulated several pathways related to apoptosis, cell cycle, and DNA damage response. Further, LY500307 sensitized GBM cells to several FDA-approved chemotherapeutic drugs including cisplatin, lomustine and temozolomide. LY500307 treatment significantly reduced the in vivo tumor growth and promoted apoptosis of GBM tumors in an orthotopic model and improved the overall survival of tumor-bearing mice in the GL26 syngeneic glioma model. Our results demonstrate that LY500307 has potential as a therapeutic agent for GBM.

Glaucoma uveítico como síndrome paraneoplásico asociado a cáncer de mama / Uveitic glaucoma as paraneoplastic syndrome with breast cancer

Introducción: Los síndromes paraneoplásicos son manifestaciones sistémicas asociadas a ciertos cánceres no relacionados con la invasión local del tumor o metástasis. Su importancia clínica radica en que pueden constituir el primer signo de enfermedad; así pues, el glaucoma uveítico constituye en este caso la primera manifestación del cáncer de mama. Método: Relato del caso, revisión de literatura, experiencia clínica y de investigación personal. Resultados: Se debe tener especial atención en la evolución favorable o no del tratamiento, si este no logra la resolución de las manifestaciones oftalmológicas, se debe investigar y valorar los factores de riesgo de neoplasia del paciente, para ello, se practicó mamografía y biopsia mamaria, y se corroboró el diagnóstico de cáncer de mama invasivo con una gammagrafía. Conclusión: Este caso ilustra la importancia de incluir manifestaciones oculares como uveítis y glaucoma como síndrome paraneoplásico asociado a cáncer de mama

Introduction: Paraneoplastic syndromes are systemic manifestations associated with certain cancers not related to the local invasion of the tumor or metastasis. The clinical importance lies in the fact that they can constitute the first sign of disease; in this case, Uveitic Glaucoma constitutes the first manifestation of breast cancer. Methods: A case report, literature review, clinical and personal research experience. Results: Special attention should be paid to the favorable or negative evolution of the treatment, if it does not achieve the resolution of the ophthalmological manifestations, investigate and assess the risk factors for neoplasia of the patient, for this, mammography and breast biopsy were performed and final diagnosis of Invasive Breast Cancer was corroborated with scintigraphy. Conclusion: This case illustrates the importance of including ocular manifestations such as uveitis and glaucoma as a paraneoplastic syndrome associated with breast cancer.