Search Results (9)

Immunotherapies, including checkpoint inhibitor antibodies, have precipitated significant improvements in clinical outcomes for melanoma. However, approximately half of patients do not benefit from approved treatments. Additionally, apart from Tebentafusp, which is approved for the treatment of uveal melanoma, there is a lack of immunotherapies directly focused on melanoma cells. This is partly due to few available targets, especially those expressed on the cancer cell surface. Chondroitin sulfate proteoglycan 4 (CSPG4) is a cell surface molecule overexpressed in human melanoma, with restricted distribution and low expression in non-malignant tissues and involved in several cancer-promoting and dissemination pathways. Here, we summarize the current understanding of the expression and functional significance of CSPG4 in health and melanoma, and we outline immunotherapeutic strategies. These include monoclonal antibodies, antibody–drug conjugates (ADCs), chimeric-antigen receptor (CAR) T cells, and other strategies such as anti-idiotypic and mimotope vaccines to raise immune responses against CSPG4-expressing melanomas. Several showed promising functions in preclinical models of melanoma, yet few have reached clinical testing, and none are approved for therapeutic use. Obstacles preventing that progress include limited knowledge of CSPG4 function in human cancer and a lack of in vivo models that adequately represent patient immune responses and human melanoma biology. Despite several challenges, immunotherapy directed to CSPG4-expressing melanoma harbors significant potential to transform the treatment landscape. Full article

Food insecurity affects nearly 50 million Americans and is linked to cardiovascular disease risk factors and health disparities. The purpose of this single-arm pilot study was to determine the feasibility of a 16-week dietitian-led lifestyle intervention to concurrently address food access, nutrition literacy, cooking skills, and hypertension among safety-net primary care adult patients. The Food Resources and Kitchen Skills (FoRKS) intervention provided nutrition education and support for hypertension self-management, group kitchen skills and cooking classes from a health center teaching kitchen, medically tailored home-delivered meals and meal kits, and a kitchen toolkit. Feasibility and process measures included class attendance rates and satisfaction and social support and self-efficacy toward healthy food behaviors. Outcome measures included food security, blood pressure, diet quality, and weight. Participants (n = 13) were on average {mean (SD)} aged 58.9 ± 4.5 years, 10 were female, and 12 were Black or African American. Attendance averaged 19 of 22 (87.1%) classes and satisfaction was rated as high. Food self-efficacy and food security improved, and blood pressure and weight declined. FoRKS is a promising intervention that warrants further evaluation for its potential to reduce cardiovascular disease risk factors among adults with food insecurity and hypertension. Full article

The purpose of this study is to assess the effects of an alternative approach to type 2 diabetes prevention. Ninety-six patients with prediabetes (age 52 (10) years; 80% female; BMI 39.2 (7.1) kg/m²) received a continuous remote care intervention focused on reducing hyperglycemia through carbohydrate restricted nutrition therapy for two years in a single arm, prospective, longitudinal pilot study. Two-year retention was 75% (72 of 96 participants). Fifty-one percent of participants (49 of 96) met carbohydrate restriction goals as assessed by blood beta-hydroxybutyrate concentrations for more than one-third of reported measurements. Estimated cumulative incidence of normoglycemia (HbA1c < 5.7% without medication) and type 2 diabetes (HbA1c ≥ 6.5% or <6.5% with medication other than metformin) at two years were 52.3% and 3%, respectively. Prevalence of metabolic syndrome, class II or greater obesity, and suspected hepatic steatosis significantly decreased at two years. These results demonstrate the potential utility of an alternate approach to type 2 diabetes prevention, carbohydrate restricted nutrition therapy delivered through a continuous remote care model, for normalization of glycemia and improvement in related comorbidities. Full article

Background and Objectives: Exertional heat stroke (EHS) survivors may be more susceptible to subsequent EHS; however, the occurrence of survivors with subsequent EHS episodes is limited. Therefore, the purpose of this study was to evaluate the incidence of participants with repeated EHS (EHS-2+) cases in a warm-weather road race across participation years compared to those who experienced 1 EHS (EHS-1). Materials and Methods: A retrospective observational case series design was utilized. Medical record data from 17-years at the Falmouth Road Race between 2003–2019 were examined for EHS cases. Incidence of EHS-2+ cases per race and average EHS cases per EHS-2+ participant were calculated (mean ± SD) and descriptive factors (rectal temperature (T_RE), finish time (FT), Wet Bulb Globe Temperature (WBGT), age, race year) for each EHS was collected. Results: A total of 333 EHS patients from 174,853 finishers were identified. Sixteen EHS-2+ participants (11 males, 5 females, age = 39 ± 16 year) accounted for 11% of the total EHS cases (n = 37/333). EHS-2+ participants had an average of 2.3 EHS cases per person (range = 2–4) and had an incidence rate of 2.6 EHS per 10 races. EHS-2+ participants finished 93 races following initial EHS, with 72 of the races (77%) completed without EHS incident. Initial EHS T_RE was not statistically different than subsequent EHS initial T_RE (+0.3 ± 0.9 °C, p > 0.050). Initial EHS-2+ participant FT was not statistically different than subsequent EHS FT (−4.2 ± 7.0 min, p > 0.050). The years between first and second EHS was 3.6 ± 3.5 year (Mode: 1, Range: 1–12). Relative risk ratios revealed that EHS patients were at a significantly elevated risk for subsequent EHS episodes 2 years following their initial EHS (relative risk ratio = 3.32, p = 0.050); however, the risk from 3–5 years post initial EHS was not statistically elevated, though the relative risk ratio values remained above 1.26. Conclusions: These results demonstrate that 11% of all EHS cases at the Falmouth Road Race are EHS-2+ cases and that future risk for a second EHS episode at this race is most likely to occur within the first 2 years following the initial EHS incident. After this initial 2-year period, risk for another EHS episode is not significantly elevated. Future research should examine factors to explain individuals who are susceptible to multiple EHS cases, incidence at other races and corresponding prevention strategies both before and after initial EHS. Full article

Ongoing Ebola virus disease outbreaks in the Democratic Republic of the Congo follow the largest recorded outbreak in Western Africa (2013–2016). To combat outbreaks, testing of medical countermeasures (therapeutics or vaccines) requires a well-defined, reproducible, animal model. Here we present Ebola virus disease kinetics in 24 Chinese-origin rhesus monkeys exposed intramuscularly to a highly characterized, commercially available Kikwit Ebola virus Filovirus Animal Non-Clinical Group (FANG) stock. Until reaching predetermined clinical disease endpoint criteria, six animals underwent anesthesia for repeated clinical sampling and were compared to six that did not. Groups of three animals were euthanized and necropsied on days 3, 4, 5, and 6 post-exposure, respectively. In addition, three uninfected animals served as controls. Here, we present detailed characterization of clinical and laboratory disease kinetics and complete blood counts, serum chemistries, Ebola virus titers, and disease kinetics for future medical countermeasure (MCM) study design and control data. We measured no statistical difference in hematology, chemistry values, or time to clinical endpoint in animals that were anesthetized for clinical sampling during the acute disease compared to those that were not. Full article

This project determined how neural circuits are affected during warming by examining sensory neurons, the neuromuscular junction, and the cardiac function and behavior of the commercially important crustacean species, the red swamp crayfish (Procambarus clarkii). Rapid inactivation of neural function in crustaceans prior to slaughter is important to limit exposure to noxious stimuli, thus improving animal welfare. This study demonstrated that as a crayfish is warmed at 1 °C/min, the heart beat stops at 44 °C. When temperature is rapidly increased, at 44 °C synaptic transmission at the neuromuscular junction ceases and primary sensory neurons stop functioning. Even though animals do not respond to stimuli after being warmed to 44 °C, if sensory neurons are returned to 20 °C saline after two minutes, they may regain function. Conversely, the neuromuscular junction does not regain function after two minutes in 44 °C saline. Examining behavior and heart rate while warming at 1 °C/min, 12 °C/min, or 46 °C/min to 80 °C indicated that at approximately 40 °C the heart rate is altered. Within 10 s at 80 °C, the heart stops with the highest heating rate. Directly placing crayfish in boiling water stopped the heart quickest, within 10 s, which likely represents denaturing of the tissue by heat. Using an impedance measure to detect a heartbeat may also be influenced by movements in the denaturing process of the tissue. A rapid increase in the temperature of the crayfish above 44 °C is key to limit its exposure to noxious stimuli. Full article

Personalized hydration strategies play a key role in optimizing the performance and safety of athletes during sporting activities. Clinicians should be aware of the many physiological, behavioral, logistical and psychological issues that determine both the athlete’s fluid needs during sport and his/her opportunity to address them; these are often specific to the environment, the event and the individual athlete. In this paper we address the major considerations for assessing hydration status in athletes and practical solutions to overcome obstacles of a given sport. Based on these solutions, practitioners can better advise athletes to develop practices that optimize hydration for their sports. Full article

This study involved a randomized, controlled, single-blind 12-month treatment study of a comprehensive nutritional and dietary intervention. Participants were 67 children and adults with autism spectrum disorder (ASD) ages 3–58 years from Arizona and 50 non-sibling neurotypical controls of similar age and gender. Treatment began with a special vitamin/mineral supplement, and additional treatments were added sequentially, including essential fatty acids, Epsom salt baths, carnitine, digestive enzymes, and a healthy gluten-free, casein-free, soy-free (HGCSF) diet. There was a significant improvement in nonverbal intellectual ability in the treatment group compared to the non-treatment group (+6.7 ± 11 IQ points vs. −0.6 ± 11 IQ points, p = 0.009) based on a blinded clinical assessment. Based on semi-blinded assessment, the treatment group, compared to the non-treatment group, had significantly greater improvement in autism symptoms and developmental age. The treatment group had significantly greater increases in EPA, DHA, carnitine, and vitamins A, B2, B5, B6, B12, folic acid, and Coenzyme Q10. The positive results of this study suggest that a comprehensive nutritional and dietary intervention is effective at improving nutritional status, non-verbal IQ, autism symptoms, and other symptoms in most individuals with ASD. Parents reported that the vitamin/mineral supplements, essential fatty acids, and HGCSF diet were the most beneficial. Full article