Perspectives on the comparative benefits of body-powered and myoelectric upper limb prostheses.

BACKGROUND: Patient access to body-powered and myoelectric upper limb prostheses in the United States is often restricted by a healthcare system that prioritizes prosthesis prescription based on cost and perceived value. Although this system operates on an underlying assumption that design differences between these prostheses leads to relative advantages and disadvantages of each device, there is limited empirical evidence to support this view. MAIN TEXT: This commentary article will review a series of studies conducted by our research team with the goal of differentiating how prosthesis design might impact user performance on a variety of interrelated domains. Our central hypothesis is that the design and actuation method of body-powered and myoelectric prostheses might affect users' ability to access sensory feedback and account for device properties when planning movements. Accordingly, other domains that depend on these abilities may also be affected. While our work demonstrated some differences in availability of sensory feedback based on prosthesis design, this did not result in consistent differences in prosthesis embodiment, movement accuracy, movement quality, and overall kinematic patterns. CONCLUSION: Collectively, our findings suggest that performance may not necessarily depend on prosthesis design, allowing users to be successful with either device type depending on the circumstances. Prescription practices should rely more on individual needs and preferences than cost or prosthesis design. However, we acknowledge that there remains a dearth of evidence to inform decision-making and that an expanded research focus in this area will be beneficial.

Material Flow Analysis and Occupational Exposure Assessment in Additive Manufacturing End-of-Life Material Management.

Additive manufacturing (AM) offers a variety of material manufacturing techniques for a wide range of applications across many industries. Most efforts at process optimization and exposure assessment for AM are centered around the manufacturing process. However, identifying the material allocation and potentially harmful exposures in end-of-life (EoL) management is equally crucial to mitigating environmental releases and occupational health impacts within the AM supply chain. This research tracks the allocation and potential releases of AM EoL materials within the US through a material flow analysis. Of the generated AM EoL materials, 58% are incinerated, 33% are landfilled, and 9% are recycled by weight. The generated data set was then used to examine the theoretical occupational hazards during AM EoL material management practices through generic exposure scenario assessment, highlighting the importance of ventilation and personal protective equipment at all stages of AM material management. This research identifies pollution sources, offering policymakers and stakeholders insights to shape pollution prevention and worker safety strategies within the US AM EoL management pathways.

Asthma policy in Illinois: A survey of school nursing and staff knowledge and implementation patterns.

OBJECTIVE: Our goal is to examine gaps in self-carry, asthma emergency protocol, and stock inhaler policy knowledge in Illinois schools. DESIGN: A 30-item REDCap cross-sectional survey developed by a team of stakeholders was disseminated. Questions assessed policy knowledge, awareness, and practices regarding asthma emergency protocols, self-carry, and stock inhalers. SAMPLE: Participants were Illinois school nurses belonging to a governmental organization listserv. MEASUREMENTS: Analysis utilized Chi-square tests, descriptive statistics, and t-tests. RESULTS: Nurses reported 36% of students on average self-carried asthma medication. Thirty percent of nurses were not aware of their emergency asthma policy and only 60% reported having an emergency asthma protocol in their school(s). Fifty-four percent of nurses were aware of stock inhaler programming. Of the 10.3% who reported a stock inhaler program, a lower frequency reported calling 911 for asthma emergencies. Perceived school asthma prevalence varied from 0%-87%. CONCLUSIONS: Our survey demonstrates large variation in knowledge and implementation of school-based asthma health policy. This is likely due to variations in health policy education dissemination. Future efforts should focus on the dissemination and implementation of school-based asthma health policies to improve their more universal adoption and better support school-based asthma management.

Inhibition of NFAT promotes loss of tissue resident uterine natural killer cells and attendant pregnancy complications in humans.

Uterine natural killer cells (uNKs) are a tissue resident lymphocyte population that are critical for pregnancy success. Although mouse models have demonstrated that NK deficiency results in abnormal placentation and poor pregnancy outcomes, the generalizability of this knowledge to humans remains unclear. Here we identify uterus transplant (UTx) recipients as a human population with reduced endometrial NK cells and altered pregnancy phenotypes. We further show that the NK reduction in UTx is due to impaired transcriptional programming of NK tissue residency due to blockade of the transcription factor nuclear factor of activated T cells (NFAT). NFAT-dependent genes played a role in multiple molecular circuits governing tissue residency in uNKs, including early residency programs involving AP-1 transcription factors as well as TGFß-mediated upregulation of surface integrins. Collectively, our data identify a previously undescribed role for NFAT in uterine NK tissue residency and provide novel mechanistic insights into the biologic basis of pregnancy complications due to alteration of tissue resident NK subsets in humans. One Sentence Summary: Role of NFAT in uterine NK cell tissue residency.

Effects of immune checkpoint inhibitor associated endocrinopathies on cancer survival.

Objectives: Immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs), of which endocrinopathies are common. We characterized endocrine and non-endocrine irAEs in cancer patients receiving ICIs, identified risk factors for their development and established whether endocrine and non-endocrine irAEs were differentially associated with improved cancer prognosis. Design and methods: Single-center, retrospective cohort study of patients with advanced or metastatic solid tumors receiving at least one ICI treatment cycle (242 men, 151 women, median age 65 years). Main outcome measures were incidence of any irAE during the study period, overall survival and time to treatment failure. Results: Non-endocrine irAEs occurred in 32% and endocrine irAEs in 12% of patients. Primary thyroid dysfunction was the most common endocrine irAE (9.5%) and the majority of endocrinopathies required permanent hormone replacement. Women had an increased risk of developing endocrine irAEs (p = 0.017). The biggest survival advantage occurred in patients who developed both endocrine and non-endocrine irAEs (overall survival: HR 0.16, CI 0.09-0.28). Time to treatment failure was also significantly improved in patients who developed endocrine irAEs (HR 0.49, CI 0.34 - 0.71) or both (HR 0.41, CI 0.25 - 0.64) but not in those who only developed non-endocrine irAEs. Conclusions: Women may have increased risk of endocrine irAEs secondary to ICI treatment. This is the first study to compare the effects of endocrine irAEs with non-endocrine irAEs on survival. Development of endocrine irAEs may confer survival benefit in ICI treatment and future, prospective studies are needed to elucidate this.

Oncogene-induced matrix reorganization controls CD8+ T cell function in the soft-tissue sarcoma microenvironment.

CD8+ T cell dysfunction impedes antitumor immunity in solid cancers, but the underlying mechanisms are diverse and poorly understood. Extracellular matrix (ECM) composition has been linked to impaired T cell migration and enhanced tumor progression; however, impacts of individual ECM molecules on T cell function in the tumor microenvironment (TME) are only beginning to be elucidated. Upstream regulators of aberrant ECM deposition and organization in solid tumors are equally ill-defined. Therefore, we investigated how ECM composition modulates CD8+ T cell function in undifferentiated pleomorphic sarcoma (UPS), an immunologically active desmoplastic tumor. Using an autochthonous murine model of UPS and data from multiple human patient cohorts, we discovered a multifaceted mechanism wherein the transcriptional coactivator YAP1 promotes collagen VI (COLVI) deposition in the UPS TME. In turn, COLVI induces CD8+ T cell dysfunction and immune evasion by remodeling fibrillar collagen and inhibiting T cell autophagic flux. Unexpectedly, collagen I (COLI) opposed COLVI in this setting, promoting CD8+ T cell function and acting as a tumor suppressor. Thus, CD8+ T cell responses in sarcoma depend on oncogene-mediated ECM composition and remodeling.

Immune-mediated thrombocytopenia and IL-6-mediated thrombocytosis observed in idiopathic multicentric Castleman disease.

Idiopathic multicentric Castleman disease (iMCD) is a rare haematological disorder characterized by generalized lymphadenopathy with atypical histopathological features and systemic inflammation caused by a cytokine storm involving interleukin-6 (IL-6). Three clinical subtypes are recognized: thrombocytopenia, anasarca, fever, renal dysfunction, organomegaly (iMCD-TAFRO); idiopathic plasmacytic lymphadenopathy (iMCD-IPL), involving thrombocytosis and hypergammaglobulinaemia; and iMCD-not otherwise specified (iMCD-NOS), which includes patients who do not meet criteria for the other subtypes. Disease pathogenesis is poorly understood, with potential involvement of infectious, clonal and/or autoimmune mechanisms. To better characterize iMCD clinicopathology and gain mechanistic insights into iMCD, we analysed complete blood counts, other clinical laboratory values and blood smear morphology among 63 iMCD patients grouped by clinical subtype. Patients with iMCD-TAFRO had large platelets, clinical severity associated with lower platelet counts and transfusion-resistant thrombocytopenia, similar to what is observed with immune-mediated destruction of platelets in immune thrombocytopenic purpura. Conversely, elevated platelet counts in iMCD-IPL were associated with elevated IL-6 and declined following anti-IL-6 therapy. Our data suggest that autoimmune mechanisms contribute to the thrombocytopenia in at least a portion of iMCD-TAFRO patients whereas IL-6 drives thrombocytosis in iMCD-IPL, and these mechanisms likely contribute to disease pathogenesis.

Electrical Stimulation of Regenerative Peripheral Nerve Interfaces (RPNIs) Induces Referred Sensations in People With Upper Limb Loss.

Individuals with upper limb loss lack sensation of the missing hand, which can negatively impact their daily function. Several groups have attempted to restore this sensation through electrical stimulation of residual nerves. The purpose of this study was to explore the utility of regenerative peripheral nerve interfaces (RPNIs) in eliciting referred sensation. In four participants with upper limb loss, we characterized the quality and location of sensation elicited through electrical stimulation of RPNIs over time. We also measured functional stimulation ranges (sensory perception and discomfort thresholds), sensitivity to changes in stimulation amplitude, and ability to differentiate objects of different stiffness and sizes. Over a period of up to 54 months, stimulation of RPNIs elicited sensations that were consistent in quality (e.g. tingling, kinesthesia) and were perceived in the missing hand and forearm. The location of elicited sensation was partially-stable to stable in 13 of 14 RPNIs. For 5 of 7 RPNIs tested, participants demonstrated a sensitivity to changes in stimulation amplitude, with an average just noticeable difference of 45 nC. In a case study, one participant was provided RPNI stimulation proportional to prosthetic grip force. She identified four objects of different sizes and stiffness with 56% accuracy with stimulation alone and 100% accuracy when stimulation was combined with visual feedback of hand position. Collectively, these experiments suggest that RPNIs have the potential to be used in future bi-directional prosthetic systems.

Application of read-across methods as a framework for the estimation of emissions from chemical processes.

The read-across method is a popular data gap filling technique with developed application for multiple purposes, including regulatory. Within the US Environmental Protection Agency's (US EPA) New Chemicals Program under Toxic Substances Control Act (TSCA), read-across has been widely used, as well as within technical guidance published by the Organization for Economic Co-operation and Development, the European Chemicals Agency, and the European Center for Ecotoxicology and Toxicology of Chemicals for filling chemical toxicity data gaps. Under the TSCA New Chemicals Review Program, US EPA is tasked with reviewing proposed new chemical applications prior to commencing commercial manufacturing within or importing into the United States. The primary goal of this review is to identify any unreasonable human health and environmental risks, arising from environmental releases/emissions during manufacturing and the resulting exposure from these environmental releases. The authors propose the application of read-across techniques for the development and use of a framework for estimating the emissions arising during the chemical manufacturing process. This methodology is to utilize available emissions data from a structurally similar analogue chemical or a group of structurally similar chemicals in a chemical family taking into consideration their physicochemical properties under specified chemical process unit operations and conditions. This framework is also designed to apply existing knowledge of read-across principles previously utilized in toxicity estimation for an analogue or category of chemicals and introduced and extended with a concurrent case study.

Carcinogénesis Oral y Epigenética

RESUMEN: A pesar de que los procesos epigenéticos son estudiados ampliamente de forma general, no se habían relacionado, hasta ahora, a las alteraciones genéticas más tradicionales asociadas en la etiopatogenia del cáncer oral. La visión de carcinogénesis tradicional y la de la epigenética convergen en las mismas vías moleculares involucradas en el desarrollo del cáncer, potenciándose durante el proceso de carcinogénesis oral. A continuación se realizará una revisón de las siguientes vías moleculares VEGF-C /VEGFR; HB-EGF /EGFR; Wnt /B-catenina y las ciclinas, desde un punto de vista genético y epigenético para establecer su conexión durante el proceso de carcinogénesis oral.

ABSTRACT: Although epigenetic processes are widely studied, no one has related them to the classical genetic processes in oral cancer etiopathogenesis. The traditional carcinogenesis and epigenetic views converge in the same molecular pathways involved in cancer development, enhancing this process. This review will approach the VEGF-C/VEGFR, HB-EGF/EGFR, Wnt /B-catenin, and cyclins molecular pathways from the genetic and epigenetic views to establish their connection during the oral cancer process.

Orthomolecular oncology: a mechanistic view of intravenous ascorbate's chemotherapeutic activity

The effect of vitamin C in cancer has been a subject of great controversy; mainly because of the inconsistent results obtained by oral intakes of ascorbate when used as an anticancer agent. We believe the intravenous application of ascorbate will provide more consistent results in cancer patients since Vitamin C blood levels attained are substantially higher in a range proven cytotoxic to malignant cells. In this article we will present and discuss our proposed mechanism on the chemotherapeutic activity exhibited by ascorbate.

Integrative medicine: a paradigm shift in medical education and practice

The use of alternative/complementary medicine has been increasing considerably. Conventional medicine must begin to address issues related to the use, safety, regulation, research and education of alternative/complementary medicine. Integrative medicine combines conventional medicine and alternative complementary practices. Integrative medicine is an innovative approach to medicine and medical education. It involves the understanding of the interaction of the mind, body and spirit and how to interpret this relationship in the dynamics of health and disease. Integrative medicine shifts the orientation of the medical practice from disease based approach to a healing based approach. It does not reject conventional medicine nor uncritically accepts unconventional practices. Integrative medicine is an effective, more fulfilling human approach to medicine based on the benefit of the patient by following good medicine practices in a scientific manner.

Ethical issues in nutritional sciences for the next century: nutrition research and counseling of nutraceutical supplementation and disease

Ethical issues pertaining research and counseling in nutritional sciences will be arising in this new century. This issue will be of great importance especially in the area of nutraceutical supplementation and disease (pharmacological nutrition). Steps to insure bioethical correctness are discussed in this paper.

Nutrition-related problems of pediatric patients with neuromuscular disorders

Children with neuromuscular disorders have special health needs that place them at risk of nutritional problems. These needs may have detrimental effects on their development, immune and respiratory system. Identified nutrition-related problems are malnutrition, obesity, food intolerance, food allergies, drug-nutrient interactions, constipation and reflux. In order to improve the nutritional status of these patients, a nutritional assessment is recommended which should include anthropometric measurements and laboratory tests.

Association between dietary fat and breast cancer in Puerto Rican postmenopausal women attending a breast cancer clinic

OBJECTIVE: A pilot case-control study was conducted to examine the possible association between dietary fat intake and the development of postmenopausal breast cancer. BACKGROUND: Studies regarding the association between dietary fat intake and the development of breast cancer among postmenopausal women are lacking in Puerto Rico. METHODS: Eighteen cases and eighteen controls were interviewed to obtain sociodemographic information, medical history and dietary fat intake. A semiquantitative food frequency questionnaire containing 67 food items was used to collect the dietary information. RESULTS: Unadjusted odds ratios (OR) and their 95 per cent confidence intervals (CI) showed a non-significant positive association for total fat intake and the development of postmenopausal breast cancer (OR = 1.57; 95 per cent CI: 0.42-5.90, p = 0.25). The same non significant positive association was found for saturated fat intake (OR = 1.57; 95 per cent CI: 0.42-5.90, p = 0.25). Polyunsaturated fat (OR = 1.25; 95 per cent CI: 0.34-4.64, p = 0.37) and monounsaturated fat (OR = 1.25; 95 per cent CI: 0.34-4.64, p = 0.37) were also positively associated with postmenopausal breast cancer, although the associations were not statistically significant. CONCLUSIONS: These results are consistent with other case-control studies that have shown non-significant positive associations between total fat and the different components of dietary fat and postmenopausal breast cancer.

Dietary fat and breast cancer: a brief update on current knowledge

Descriptive epidemiologic data suggest a relationship between consumption of high fat diets and breast cancer; although these data can be potentially confounded by other causative exposures. Results of published case-control and cohort studies are inconclusive. Nevertheless, dietary fat significantly affects mammary tumorigenesis in mice and rats in laboratory experiments. We will review current epidemiologic and animal studies, explain the possible mechanisms of how dietary fat may affect breast cancer, and provide preliminary dietary recommendations.

Folate supplementation and neural tube defects: a review of a Public Health issue

Folate deficiency is one of today's most common vitamin deficiencies in women. Women who consume a low level of folate during pregnancy are at risk for poor pregnancy outcomes including neural tube defects (NTD). However, other factors such as heredity, social class, maternal age, birth order, maternal diet, length of time between pregnancies, maternal zinc deficiency, use of anticonvulsant drugs, abnormal homocysteine metabolism and the use of oral contraceptives, have also been implicated as causes of NTD. Animal studies have shown that fetuses are highly dependent on the folate status of the mother. In addition, several retrospective and prospective human studies have provided evidence that folate lowers the incidence of NTD