Enhanced safety and efficacy of protease-regulated CAR-T cell receptors.

Regulatable CAR platforms could circumvent toxicities associated with CAR-T therapy, but existing systems have shortcomings including leakiness and attenuated activity. Here, we present SNIP CARs, a protease-based platform for regulating CAR activity using an FDA-approved small molecule. Design iterations yielded CAR-T cells that manifest full functional capacity with drug and no leaky activity in the absence of drug. In numerous models, SNIP CAR-T cells were more potent than constitutive CAR-T cells and showed diminished T cell exhaustion and greater stemness. In a ROR1-based CAR lethality model, drug cessation following toxicity onset reversed toxicity, thereby credentialing the platform as a safety switch. In the same model, reduced drug dosing opened a therapeutic window that resulted in tumor eradication in the absence of toxicity. SNIP CARs enable remote tuning of CAR activity, which provides solutions to safety and efficacy barriers that are currently limiting progress in using CAR-T cells to treat solid tumors.

An engineered ultrahigh affinity bi-paratopic uPAR targeting agent confers enhanced tumor targeting.

Urokinase-type plasminogen activator receptor (uPAR) is overexpressed on tumor cells in multiple types of cancer and contributes to disease progression and metastasis. In this work, we engineered a novel bi-paratopic uPAR targeting agent by fusing the binding domains of two native uPAR ligands: uPA and vitronectin, with a flexible peptide linker. The linker length was optimized to facilitate simultaneous engagement of both domains to their adjacent epitopes on uPAR, resulting in a high affinity and avid binding interaction. Furthermore, the individual domains were affinity-matured using yeast surface display and directed evolution, resulting in a bi-paratopic protein with affinity in the picomolar to femtomolar range. This engineered uPAR targeting agent demonstrated significantly enhanced tumor localization in mouse tumor models compared to the native uPAR ligand and warrants further investigation as a diagnostic and therapeutic agent for cancer.

A community-based pragmatic, controlled trial for preventing and reducing oral diseases among 1-6-year-old children visiting Anganwadi centers, under the Integrated Child Development Scheme, India.

BACKGROUND: Early childhood caries (ECC) has reached epidemic proportions affecting millions of children worldwide. Its prevention becomes imperative owing to the significant morbidity and financial implications involved with its treatment. The Integrated Child Development Scheme (ICDS), launched in India to provide mid-day meals, pre-school education and primary healthcare to children, can be utilised to counsel and deliver oral health education to mothers. The purpose of the study is to compare the effect of an oral health care package (OHCP) with usual care on the change in dental disease status among 1 to 3-year-old children at Anganwadi centres (AWC) in periurban areas of Chandigarh and rural areas of Cuttack, Orissa over a follow-up period of three years. METHODS: Two geographically distant ICDS blocks would be selected at each of the two study sites and would be randomly allocated to intervention and control group. Closely located AWCs under each of the selected blocks shall constitute the study setting. OHCP would be delivered to the mothers of the 1-6-year-old children enrolled in the AWCs of the experimental group whereas mothers under control group would receive usual care advice available at the AWCs. DISCUSSION: ECC prevention had conventionally focused upon testing effectiveness of programs targeting behaviour change among the caregivers and children, but surprisingly minimal efforts have been made to seek translation of these efforts into reduction of ECC at the community level. The present study has two components; testing effect of altering maternal and child behavioral aspects on ECC incidence through cohort follow up of 1-3-year-old children for three consecutive years and cross-sectional follow up of all available 1-6-year old children at the selected AWCs at regular intervals to look for change in prevalence of ECC at community level. In other regions of the world surveys of ECC prevalence before and after the intensive educational programs have shown a significant reduction in ECC prevalence. A similar decline can be anticipated through this program. TRIAL REGISTRATION: This trial has been prospectively registered at Clinical Trials Registry, India (CTRI/2019/02/017556, 08 February 2019).

Association of occupational stress factors on nicotine dependence among patients visiting dental care unit of Indo-Tibetian border police force station in India.

BACKGROUND: Tobacco use is the foremost preventable cause of death and disease in the world today and work strain might be related with nicotine dependence by its provoking effect. OBJECTIVE: To assess the association between occupational stress and nicotine dependence. MATERIAL AND METHODS: A cross sectional survey was conducted among 200 subjects visiting a satellite dental clinic of Swami Devi Dyal Hospital and Dental College, Barwala, Panchkula, India. Nicotine dependence was measured using the Fagerstrom Test for Nicotine Dependence (FTND). The extent of the stress factors experienced at work was assessed using the Effort-Reward Imbalance scale (ERI). Chi-square test and multiple logistic regression analysis were employed for statistical analysis. Confidence level and level of significance were set at 95% and 5% respectively. RESULTS: The results of bivariate analysis revealed association of occupational stress with age, marital status, educational status, level of nicotine dependence, frequency of cigarette smoking and religious attendance. However, multivariate analysis elicited the significant association of occupational stress with only two variables, level of nicotine dependence and frequency of smoking. CONCLUSION: Occupational stress was found to be associated with nicotine dependence in the present study implying a need of other tranquil measures to be incorporated for the relief of work related stress.

Dietary patterns and risk of oral and oropharyngeal cancers: A systematic review and meta-analysis.

Systematic evaluation of evidence assessing the role of dietary patterns on oral and oropharyngeal (OOP) cancer risk can provide a better understanding of their relationship. This systematic review of observational studies aimed to integrate the most recent evidence on the relationship between posteriori and priori dietary patterns and risk of development of OOP cancers. Studies were retrieved from Embase, PubMed, and Web of Science, and a total of 22 publications were included in the systematic review, of which 17 were included in the meta-analysis. Summary risk was estimated for highest versus lowest intakes of most common identified food groups and risk of OOP cancers using the random effect, generic inverse variance method. The quality of the included studies was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS) for Case-Control and Cohort studies. As per pooled analysis, consumption of healthy patterns may decrease the risk of OOP cancers by 43 %, and that of western patterns may increase this risk by 62 %. The pooling of data from ten studies analysing priori patterns and OOP cancers shows that the Mediterranean diet and diverse diet reduce the risk of such cancers, and a pro-inflammatory diet escalates the risk. On NOS, 11 studies were good in quality and 11 were moderate. Adopting a diet rich in fruits and vegetables and low intake of snacks and animal fats can potentially reduce the likelihood of developing OOP cancers. Encouraging Mediterranean diet, diverse diet and anti-inflammatory food components would be beneficial in the prevention and control of OOP cancers.

Powered versus manual toothbrushes for plaque removal and gingival health amongst 55 and older individuals: A systematic review and meta-analysis.

OBJECTIVE: To compare manual and powered toothbrushes in older adults and to culminate available clinical evidence concerning efficiency with respect to plaque removal and reduced gingivitis. BACKGROUND: Manual dexterity decreases with age, negatively impacting daily activities, including oral hygiene practices. Effective plaque control in this age group is directly related to nutrition and overall health. Therefore, developing oral health interventions tailored to the ageing population is essential. MATERIAL AND METHODS: This systematic review was registered with PROSPERO (Registration No. CRD42023415876). Five electronic databases were searched to identify randomized controlled trials published from inception until March 2023. The risk of bias was assessed using the Cochrane Risk of Bias Tool. Meta-analyses were also performed for gingival, plaque, and bleeding indices. RESULTS: A total of 2118 records were identified, and six eligible publications were retrieved. Comparison of Plaque Indices between powered and manual toothbrushes showed a Standard mean difference (SMD) of -0.10; 95% CI [-0.37, 0.18] (p = .38). Comparison of the gingival index and bleeding index between powered and manual toothbrushes showed an SMD of -0.28; 95% CI [-0.72, 0.16] (p = .22) and SMD of -0.03 [-0.38, 0.32] (p = .84), respectively. CONCLUSION: According to the available literature, this study suggests the need for more streamlined research to support the superiority of either powered or manual toothbrushes in improving oral health (as measured by the indices) among the older population. The results will hence have significant reverberations for older adults looking to improve their oral hygiene practices.

Convergence of inflammatory response: Salivary cytokine dynamics in coronavirus disease 2019 and periodontal disease.

Background: Periodontal disease is associated with immune dysregulation, and cytokines released can add on to the coronavirus disease 2019 (COVID-19)-associated cytokine storm, further worsening the related adverse outcomes. Specific studies investigating cytokine levels in COVID-19 patients with periodontal disease are lacking. Examining the correlation between these conditions could aid in categorizing risk categories, determining referrals, and strengthening oral hygiene protocols. The current study sought to evaluate cytokine levels in the saliva of COVID-19-positive patients with and without periodontal disease. Materials and Methods: Twenty-six COVID-19-positive patients were subjected to periodontal examination, saliva collection, and assessment of cytokine levels through cytokine bead-based multiplex assay, using fluorescence-encoded beads with flow cytometry (BD FACS LSRFortessa). Eleven cytokines were assessed (interleukin [IL] 2, 4, 6, 10, 17A, and interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-α), chemokine ligand 2 (CCL2/monocyte chemoattractant protein-1), C-X-C motif chemokine ligand (CXCL) 8/IL 8, CXCL 9/monokine-induced gamma interferon [MIG]), and CXCL 10 (chemokine IFN-gamma inducible protein 10 kDa). The cytokine levels of the recruited subjects were also compared graphically with the salivary cytokine levels reported in the literature for health, COVID-19, and periodontal disease alone. Results: Out of 26 COVID-19-positive patients, 17 had periodontal disease. Levels of all cytokines were raised in patients with both diseases when compared to values reported in literature for health, periodontal disease alone, or COVID-19 alone. However, there was no statistical difference among the recruited subjects for IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-gamma, TNF-α, CCL2, CXCL 8, and CXCL 10. MIG levels were found to be higher in periodontally healthy, COVID-19-positive subjects (P = 0.01). Conclusions: Periodontal disease might contribute to the COVID-19-induced cytokine storm, potentially amplifying its impact.

Does Tobacco Use Enhance the Risk of SARS-CoV-2 Infection: Evidence from Eastern Indian Population.

Background: Tobacco consumption causes altered immune and inflammatory responses which lead to various respiratory diseases such as asthma and chronic obstructive pulmonary disease, as well as cardiovascular and cerebrovascular disorders. Studies have only confirmed the harmful effects of tobacco consumption on the severity of COVID-19. The present study aimed to explore the association between tobacco consumption and the initiation of COVID-19. Methods: This retrospective cohort study was conducted to explore the relationship between tobacco consumption and COVID-19. A brief closed-ended, self-structured questionnaire was prepared to record participants' responses. The Participants included the individuals who visited Rajendra Institute of Medical Sciences (RIMS), Ranchi, India for the COVID-19 diagnostic test. The statistical analysis was performed using SPSS software (version 24). The chi-square test and logistic regression analysis were also used to predict the odds of getting infected with COVID-19. Findings: A total of 521 valid responses were obtained and subjected to analysis. Moreover, 256 participants (49.13%) were COVID-19 positive and 57 participants (10.94%) were tobacco users. The odds ratio of tobacco consumption was higher in COVID-19-positive patients compared to COVID-19-negatives (OR=1.78; 95% CI 1.01, 3.13). The current tobacco users had a higher risk of developing COVID-19 as compared to the former users (OR=4.8; 95% CI 1.39, 16.61). The frequency and duration of tobacco use also affected the COVID-19 infectivity rate but these were statistically insignificant. Conclusion: The COVID-19 positivity rate was significantly higher in tobacco users, especially in current tobacco users as compared to former users. Nevertheless, gender and occupation had no significant effect on COVID-19 incidence in this study.

An engineered ligand trap inhibits leukemia inhibitory factor as pancreatic cancer treatment strategy.

Leukemia inhibitory factor (LIF), a cytokine secreted by stromal myofibroblasts and tumor cells, has recently been highlighted to promote tumor progression in pancreatic and other cancers through KRAS-driven cell signaling. We engineered a high affinity soluble human LIF receptor (LIFR) decoy that sequesters human LIF and inhibits its signaling as a therapeutic strategy. This engineered 'ligand trap', fused to an antibody Fc-domain, has ~50-fold increased affinity (~20 pM) and improved LIF inhibition compared to wild-type LIFR-Fc, potently blocks LIF-mediated effects in pancreatic cancer cells, and slows the growth of pancreatic cancer xenograft tumors. These results, and the lack of apparent toxicity observed in animal models, further highlights ligand traps as a promising therapeutic strategy for cancer treatment.

An engineered antibody binds a distinct epitope and is a potent inhibitor of murine and human VISTA.

V-domain immunoglobulin (Ig) suppressor of T cell activation (VISTA) is an immune checkpoint that maintains peripheral T cell quiescence and inhibits anti-tumor immune responses. VISTA functions by dampening the interaction between myeloid cells and T cells, orthogonal to PD-1 and other checkpoints of the tumor-T cell signaling axis. Here, we report the use of yeast surface display to engineer an anti-VISTA antibody that binds with high affinity to mouse, human, and cynomolgus monkey VISTA. Our anti-VISTA antibody (SG7) inhibits VISTA function and blocks purported interactions with both PSGL-1 and VSIG3 proteins. SG7 binds a unique epitope on the surface of VISTA, which partially overlaps with other clinically relevant antibodies. As a monotherapy, and to a greater extent as a combination with anti-PD1, SG7 slows tumor growth in multiple syngeneic mouse models. SG7 is a promising clinical candidate that can be tested in fully immunocompetent mouse models and its binding epitope can be used for future campaigns to develop species cross-reactive inhibitors of VISTA.

Structure and Functional Binding Epitope of V-domain Ig Suppressor of T Cell Activation.

V-domain immunoglobulin (Ig) suppressor of T cell activation (VISTA) is an immune checkpoint protein that inhibits the T cell response against cancer. Similar to PD-1 and CTLA-4, a blockade of VISTA promotes tumor clearance by the immune system. Here, we report a 1.85 Å crystal structure of the elusive human VISTA extracellular domain, whose lack of homology necessitated a combinatorial MR-Rosetta approach for structure determination. We highlight features that make the VISTA immunoglobulin variable (IgV)-like fold unique among B7 family members, including two additional disulfide bonds and an extended loop region with an attached helix that we show forms a contiguous binding epitope for a clinically relevant anti-VISTA antibody. We propose an overlap of this antibody-binding region with the binding epitope for V-set and Ig domain containing 3 (VSIG3), a purported functional binding partner of VISTA. The structure and functional epitope presented here will help guide future drug development efforts against this important checkpoint target.

Predictors determining the duration of hospital stay among patients admitted with singlefractures / Predictores que determinan la duración de la estancia hospitalaria en pacientes ingresados con fracturasúnicas

Introduction: Fractures pose a tremendous burden on the health care systems due to the prolonged duration of admission. Addressing various determinants that prolong hospital stay will help minimize the cost of treatment. Objective: To study the determinants associated with the duration of hospital stay among patients admitted with fractures. Methods: This was a retrospective observational study conducted at a private tertiary care hospital in Mangalore. A semi-structured proforma was used for collecting data from the medical records. Results: The mean age of the 124 patients were 48.3±21.4 years. The majority were males [69(55.6 por ciento)] and were from urban areas [86(69.3 por ciento)]. Co-morbidities were present among 69(55.6 por ciento) patients. Out of the total patients, 8(6.4 por ciento) were alcoholics, and 10(8.1 por ciento) were tobacco smokers. The majority [50(40.3 por ciento)] had fracture of the femur. Five (4 por ciento) patients developed complications during the post-operative period. Seventy-eight (62.9 por ciento) patients had medical insurance facilities. The mean duration of hospital stay was 9.6±3.2 days among the patients. The mean duration of hospital stay among patients (n=115) before surgery was 2.4±1.6 days. Increased pre-operative stay, increasing age, rural residential status, open type of fracture, and being given general anaesthesia for the operative procedure were significant predictors determining the period of stay among patients in the hospitals. Alcoholic status independently influenced the period of stay in the pre-operative period. Conclusion: Both patient and treatment characteristics were important determinants associated with the duration of hospital stay. Targeting these predictors will help to manage in-patients better and shorten their duration of hospital stay(AU)

Introducción: Las fracturas suponen una enorme carga para los sistemas sanitarios debido a la duración prolongada del ingreso. Abordar varios determinantes que prolongan la estadía en el hospital ayudará a minimizar el costo del tratamiento. Objetivo: Estudiar los determinantes asociados a la duración de la estancia hospitalaria en pacientes ingresados con fracturas. Métodos: Este es un estudio observacional retrospectivo realizado en un hospital privado de atención terciaria en Mangalore. Se utilizó una proforma semiestructurada para la recolección de datos de las historias clínicas. Resultados: La edad media de los 124 pacientes fue de 48,3±21,4 años. La mayoría eran hombres [69 (55,6 percent)] y de áreas urbanas [86 (69,3 percent)]. Las comorbilidades estuvieron presentes en 69 (55,6 percent) pacientes. Del total de pacientes, 8 (6,4 percent) eran alcohólicos y 10 (8,1 percent) fumadores. La mayoría [50 (40,3 percent)] tenía fractura de fémur. Cinco (4 percent) pacientes desarrollaron complicaciones durante el postoperatorio. Setenta y ocho (62,9 percent) pacientes tenían seguro médico. La duración media de la estancia hospitalaria fue de 9,6±3,2 días entre los pacientes. La duración media de la estancia hospitalaria de los pacientes (n=115) antes de la cirugía fue de 2,4±1,6 días. El aumento de la estancia preoperatoria, el aumento de la edad, el estado residencial rural, el tipo de fractura abierta y la anestesia general para el procedimiento quirúrgico fueron predictores significativos que determinaron el período de estancia entre los pacientes en los hospitales. El estado alcohólico influyó de forma independiente en el tiempo de estancia en el preoperatorio. Conclusión: Tanto las características del paciente como las del tratamiento fueron determinantes importantes asociadas con la duración de la estancia hospitalaria. Abordar estos predictores ayudará a manejar mejor a los pacientes hospitalizados y acortar la duración de su estadía en el hospital(AU)

Perception of health care providers toward geriatric oral health in Belgaum district: A cross-sectional study.

OBJECTIVES: To access knowledge and practices related to the oral health of geriatrics among the health care providers practicing in urban and rural areas. BACKGROUND: Older adults have identified a number of barriers that contribute to lack of dental service use. However, barriers that clinicians encounter in providing dental treatment to older adults are not as clear-cut. MATERIALS AND METHODS: 236 health professionals (of allopathy, ayurveda, and homeopathy) from urban and rural areas were assessed by means of structured questionnaire related to oral health practices and beliefs. RESULTS: Doctors practicing in urban areas assessed dental care needs more frequently (P = 0.038) and performed greater practices related to oral health of geriatrics (P = 0.043) than the doctors practicing in primary health care (PHC) centers (rural) (P = 0.038). CONCLUSION: Owing to the relative lack of knowledge among rural practitioners, there is a need to integrate primary health care with oral care in rural areas.

Plasma fibrinogen degradation products in oral submucous fibrosis.

CONTEXT: Plasma fibrinogen degradation products (FDPs) and oral submucous fibrosis (OSMF). BACKGROUND: OSMF is a chronic, progressive, scarring disease of multifactorial etiology. Areca nut is found to be the main cause of this disease. But it has been found in the routine clinical practice that some individuals with the habit of areca nut chewing may not show any clinical evidence of OSMF, while some individuals without the habit of areca nut chewing are found to have OSMF. So, there must be some other factors associated with OSMF. Recently, plasma FDPs have been identified as an early indicator of disease in OSMF patients. A systematic review of their role would help to elucidate whether there is an association of these FDPs in the pathogenesis of OSMF or not. OBJECTIVE: To review studies reported in the literature elucidating the role of these plasma FDPs in OSMF. MATERIALS AND METHODS: Articles were searched in PubMed; MEDLINE using appropriate key words like "plasma fibrinogen degradation products" and "oral submucous fibrosis." Hand search of journals was also performed. Articles were reviewed and analyzed. RESULTS: The search strategy revealed nine relevant articles which studied the role of these plasma FDPs in the etiopathogenesis of OSMF and further progression of this disease with the increased clinical grades and the risk of carcinoma, but the exact role of these factors is still obscure. CONCLUSION: The data validate the role of plasma FDPs in the etiopathogenesis of OSMF. Studies with a large sample size are still required to evaluate the definite association between these FDPs and OSMF. It has the advantage of being a noninvasive method to evaluate the stage of OSMF patients, instead of using the invasive techniques like biopsy.

Role of Lycopene in Preventing Oral Diseases as a Nonsurgical Aid of Treatment.

Without pigments, we are nothing. Life presents us with a kaleidoscope of colors. From the green grass of home to a forest's ruddy autumn hues, we are surrounded by living colors. Living things obtain their colors, with few exceptions, from natural pigments. In addition to their role in coloration, natural pigments carry out a variety of important biological functions. Of the various classes of pigments in nature, the carotenoids are among the most widespread and important ones, especially due to their varied functions. Lycopene is a red plant pigment found in tomatoes, apricots, guavas, watermelons, papayas, and pink grapefruits, with tomatoes being the largest contributor to the dietary intake of humans. Lycopene exhibits higher singlet oxygen quenching ability. Due to its strong color and nontoxicity, it is a useful food coloring agent. Moreover, it plays a multifunctional role as a nonsurgical aid in the treatment of oral diseases like leukoplakia, oral submucous fibrosis, lichen planus, oral squamous cell carcinoma, and also prevents the destruction of periodontal tissues. This review article focuses mainly on the role of lycopene in the prevention of various oral diseases.

Knowledge regarding Ebola Hemorrhagic Fever among private dental practitioners in Tricity, India: A cross-sectional questionnaire study.

BACKGROUND: Ebola viral fever, a highly contagious haemorrhagic disease has today become a major public health concern in the developing countries worldwide. AIM: The purpose of this study was to assess knowledge among dental practitioners regarding Ebola Haemorrhagic Fever (Ebola HF) in Tricity, (Chandigarh, Panchkula and Mohali). MATERIALS AND METHODS: A total of 500 private dental practitioners were randomly approached to participate in this cross-sectional survey. A self-structured, closed ended questionnaire was administered to each participant to record demographic and professional characteristics followed by their knowledge regarding Ebola HF. Knowledge section included questions related to communicability; symptomatology and diagnostics; at-risk individuals; prevention and treatment; and, virus characteristics of Ebola HF. RESULTS: The results were expressed in percentages. Multivariable linear regression analysis was carried out to assess the association of participants's demographic and professional characteristics with the knowledge scores. Statistically significant difference was seen when mean knowledge scores were compared based on the locality and qualification of the participants (P < 0.05). CONCLUSION: Dental practitioners from urban areas with higher qualification had better knowledge yet there were notable deficiencies regarding the virus characteristics, diagnostics, elimination and treatment.

IgGA: a "cross-isotype" engineered human Fc antibody domain that displays both IgG-like and IgA-like effector functions.

All clinically approved antibodies are of the IgG isotype and mediate the clearance of target cells via binding to Fcγ receptors and complement (C1q). Even though IgA can elicit powerful cytotoxic action via FcαRI receptor binding, IgA antibodies have not been amenable to therapeutic development. Here, we report the engineering of a "cross-isotype" antibody, IgGA, which combines the effector functions of both IgG and IgA. IgGA binds to FcαRI with an affinity comparable to that of IgA, and to the activating Fcγ receptors, FcγRI and FcγRIIa, with high affinity, and displays increased binding to C1q compared to IgG. Unlike trastuzumab-IgG, trastuzumab-IgGA potently activates both neutrophils and macrophages to kill Her2(+) cancer cells. Furthermore, IgGA mediates greater complement-dependent cytotoxicity than IgG1 or IgA antibodies. The multitude of IgGA effector functions could be important for therapeutic purposes and highlights the concept of engineering antibodies that combine effector functions from multiple antibody isotypes.

COMPUTER DETECTION APPROACHES FOR IDENTIFICATION OF PHASIC ELECTROMYOGRAPHIC (EMG) ACTIVITY DURING HUMAN SLEEP.

BACKGROUND: Examination of spontaneously occurring phasic muscle activity from the human polysomnogram may have considerable clinical importance for patient care, yet most attempts to quantify the detection of such activity have relied upon laborious and intensive visual analyses. We describe in this study innovative signal processing approaches to this issue. METHODS: We examined multiple features of surface electromyographic signals based on 16,200 individual 1-second intervals of low impedance sleep recordings. We validated which of those features most closely mirrored the careful judgments of trained human observers in making discriminations of the presence of short-lived (100-500 msec) phasic activity, and also examined which features provided maximal differences across 1-second intervals and which features were least susceptible to residual levels of amplifier noise. RESULTS: Our data suggested particularly promising and novel features (e.g., Non-linear energy, 95(th) percentile of Spectral Edge Frequency) for developing automated systems for quantifying muscle activity during human sleep. CONCLUSIONS: The EMG signals recorded from surface electrodes during sleep can be processed with techniques that reflect the visually based analyses of the human scorer but also offer potential for discerning far more subtle effects, Future studies will explore both the clinical utility of these techniques and their relative susceptibility to and/or independence from signal artifacts.