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PubMed2003

Hepatitis flares and hepatitis B e antigen seroconversion: implication in anti-hepatitis B virus therapy.

Hepatitis flares or acute exacerbations, defined as an abrupt elevation of serum alanine aminotransferase (ALT) over fivefold the upper limit of normal (ULN), of chronic hepatitis B virus (HBV) infection are the results of HLA-I restricted, cytotoxic T lymphocyte (CTL)-mediated immune response against HBV and its downstream mechanisms. Higher ALT levels reflect a more vigorous immune response and a more extensive hepatolysis that, in the extreme situation, may lead to decompensation and failure. In contrast, higher ALT also reflects a more robust immune clearance of HBV and, therefore, a higher chance of HBV-DNA loss and hepatitis B e antigen (HBeAg) seroconversion, both in the setting of natural course and drug therapy. Alanine aminotransferase of fivefold the ULN appears to be a significant cut-off level to categorize the patients in terms of endogenous immune response against HBV. Patients with ALT levels less than fivefold the ULN or those with a less vigorous immune response require immunomodulation to induce robust immune response to enhance HBV clearance. In contrast, those with a more vigorous immune response or those with ALT flare over fivefold the ULN should be monitored closely for spontaneous HBV clearance/HBeAg seroconversion or to start direct antiviral therapy in time to prevent the occurrence or deterioration of hepatic decompensation. In conclusion, a better understanding of the pathogenetic mechanisms and natural course of hepatitis flares, wiser selection of patients and the timing of drug therapy are crucial to achieve better treatment results.

Alanine Transaminase↗
PubMed2000

Leisure-time physical activity at weekends and the risk of Type 2 diabetes mellitus in Japanese men: the Osaka Health Survey.

AIMS: To investigate association between leisure-time physical activity at weekends and the risk of developing Type 2 diabetes mellitus (DM). METHODS: Prospective examination of 6,013 Japanese men aged 35-60 years who were free of DM, impaired fasting glycaemia, or hypertension at study entry. Type 2 DM was defined by a fasting plasma glucose level > or = 7.0 mmol/l or a 2-h post-load plasma glucose level > or =11.1 mmol/l. Data on physical activity obtained from questionnaires consisted of overall leisure-time physical activity weekly and leisure-time physical activity at weekends. RESULTS: During the 59,966 person-years follow-up, 444 cases developed Type 2 DM. Regular physical exercise at least once a week was associated with a reduced risk of Type 2 DM. After adjustments for age, body mass index, daily alcohol consumption, smoking habits, blood pressure levels and a parental history of Type 2 DM, men who engaged in regular physical exercise at least once a week had a relative risk of Type 2 DM of 0.75 (95% CI, 0.61-0.93) compared with men engaging in exercise less often. Even vigorous activity only once a week at weekends was associated with a reduced risk of Type 2 DM. Men who engaged in vigorous activity at least once a week at weekends had a multiple-adjusted relative risk of Type 2 DM of 0.55 (95% CI, 0.35-0.88) compared with sedentary men. CONCLUSIONS: Regular physical exercise at least once a week and vigorous activity even only once a week at weekends are associated with a decreased risk of Type 2 DM.

Adult↗
PubMed2002

Physiologic changes after diet combined with structured aerobic exercise or lifestyle activity.

Moderate intensity physical activity achieved through changes in lifestyle may promote weight management. However, little is known about changes in physiologic and metabolic variables when patients lose weight using moderate intensity lifestyle activity instead of traditional structured vigorous aerobic exercise. To compare changes in resting metabolic energy expenditure (REE), fat mass (FM), and fat-free mass (FFM) associated with a 12-week weight loss program combined with either: (1) aerobic exercise (AER); or (2) lifestyle activity (LIFE), we randomized 39 overweight adults (mean body mass index [BMI] = 30.9 +/- 2.8 kg/m(2)) to either diet plus AER (N = 18) or diet plus LIFE (N = 21). Both groups consumed a self-selected diet of 1,200 to 1,800 kcal/d (5,021 to 7,531 kJ/d). The AER group performed vigorous aerobic exercise for up to 45 minutes 3 to 4 d/wk. The LIFE group accumulated 30 minutes of moderate intensity physical activity on most days of the week. Compliance with the respective protocols was monitored on a weekly basis. REE was measured before and after treatment via open-circuit spirometry. The AER group decreased body weight by 8.4% (P<.001)while the LIFE had a reduction of 6.7% (P <.001) after treatment. Over the course of the interventions, the AER and LIFE groups experienced 10.9% (P <.001) and 10.2% (P <.001) reductions in REE, respectively. Aerobic exercise did not prevent reductions in REE to a greater extent than did lifestyle activity in patients consuming a reduced calorie diet. Change in REE was not related to changes in FFM or FM for either group, and there were no differences between groups in reductions of REE, weight, FM, or FFM. A program of diet plus lifestyle physical activity may be a suitable alternative for dieting adults who have difficulty adhering to a program of vigorous activity.

Adipose Tissue↗
PubMed2006

Amount and intensity of physical activity, fitness, and serum lipids in pre-menopausal women.

The aim of the study was to determine the association between the amount and the intensity of physical activity (PA) and lipid profile and fitness in pre-menopausal women. A cross-sectional study was conducted, sampling was stratified according to two age groups and two levels of PA, as assessed by the Minnesota Leisure Time PA Questionnaire. Serum lipid profile and sex hormones were measured. The study included 403 women. Total energy expenditure on PA was directly associated with HDL-cholesterol and inversely with atherogenic index. When intensity was analyzed, only moderate PA was associated with a desirable lipid profile. A decrease of 1.59 mg/dL (standard error [SE] = 0.77) and 0.07 units (SE = 0.02) in LDL-cholesterol and atherogenic index, respectively, and an increase of 1.02 mg/dL (SE = 0.34) in HDL-cholesterol were observed per each 100 MET . min/day spent in moderate PA. After adjusting for body fat mass, the association between moderate PA and LDL-cholesterol was no longer statistically significant (regression coefficient = - 1.21; SE = 0.81) whereas the association between moderate PA and atherogenic index (regression coefficient = - 0.05; SE = 0.02) and HDL-cholesterol (regression coefficient = 0.98; SE = 0.35) remained statistically significant. Only vigorous PA was associated with VO2max. VO2max increased 2.35 mL/kg (SE = 0.39) per each 100 MET . min/day spent in vigorous PA. Only moderate PA is associated with a lower LDL-cholesterol and atherogenic index, and higher HDL-cholesterol. The association between PA and LDL is dependent on body fat mass, but the association between PA and HDL is independent of it. Only vigorous intensity PA is associated with fitness.

Adolescent↗
PubMed1984

Placental contribution to lactate production by the human fetoplacental unit.

Umbilical cord blood levels of lactate, base deficit, and pH were measured in 452 liveborn infants. In vigorous newborns, the mean umbilical arterial and venous concentrations of lactate were lowest with elective cesarean section, higher with cesarean section performed during labor, and highest with vaginal delivery (P less than .001). This suggests a rise in the fetal lactate level in response to labor. However, there was no concomitant increase in the mean umbilical arteriovenous lactate differences, indicating that both fetus and placenta increase their lactate production proportionately with labor. Depressed newborns had higher umbilical lactate levels than vigorous newborns irrespective of the method of delivery (P less than .001). Depressed newborns also had a higher mean umbilical arteriovenous lactate difference than vigorous newborns (P less than .001). This suggests that, under conditions that lead to neonatal depression, the fetus is the major source of the increased lactate produced, with a smaller contribution from the placenta. The fetal lactate level may be a good indicator of fetal stress in labor.

Acidosis↗
PubMed1993

The association of changes in physical-activity level and other lifestyle characteristics with mortality among men.

BACKGROUND: Recent trends toward increasing physical exercise, stopping cigarette smoking, and avoiding obesity may increase longevity. We analyzed changes in the lifestyles of Harvard College alumni and the associations of these changes with mortality. METHODS: Men who were 45 to 84 years of age in 1977 and who had reported no life-threatening disease on questionnaires completed in 1962 or 1966 and again in 1977 were classified according to changes in lifestyle characteristics between the first and second questionnaires. We analyzed changes in their level of physical activity, cigarette smoking, blood pressure, and body weight, and the relation of these factors to mortality between 1977 and 1985. RESULTS: Of the 10,269 men, 476 died during this period (which totaled 90,650 man-years of observation). Beginning moderately vigorous sports activity (at an intensity of 4.5 or more metabolic equivalents) was associated with a 23 percent lower risk of death (95 percent confidence interval, 4 to 42 percent; P = 0.015) than not taking up moderately vigorous sports. Quitting cigarette smoking was associated with a 41 percent lower risk (95 percent confidence interval, 20 to 57 percent; P = 0.001) than continuing smoking, but with a 23 percent higher risk than constant nonsmoking. Men with recently diagnosed hypertension had a lower risk of death than those with long-term hypertension (relative risk, 0.75; 95 percent confidence interval, 0.55 to 1.02; P = 0.057), as did men with consistently normal blood pressure (relative risk, 0.52; 95 percent confidence interval, 0.40 to 0.68; P < 0.001). Maintenance of lean body mass was associated with a lower mortality rate than long-term, recent, or previous obesity. The associations between changes in lifestyle and mortality were independent and were largely undiminished by age. Our findings on death from coronary heart disease mirrored those on death from all causes. CONCLUSIONS: Beginning moderately vigorous sports activity, quitting cigarette smoking, maintaining normal blood pressure, and avoiding obesity were separately associated with lower rates of death from all causes and from coronary heart disease among middle-aged and older men.

Aged↗
PubMed2004

Serum antibody responses after intradermal vaccination against influenza.

BACKGROUND: If found to be safe and immunogenic, reduced doses of influenza vaccine given by the intradermal route could increase the number of available doses of vaccine. METHODS: In an open-label study, we randomly assigned 119 subjects to receive an intradermal injection of trivalent inactivated influenza vaccine, containing 6 mug of hemagglutinin for each antigen (40 percent of the usual dose), and 119 to receive an intramuscular injection of the standard dose of 15 mug of hemagglutinin for each antigen. The two groups were subdivided according to age (18 to 60 years and older than 60 years). RESULTS: Among subjects who were 18 to 60 years of age, serum antibody responses were vigorous and did not differ significantly between the intradermal and intramuscular groups, and all subjects had hemagglutination-inhibition (HAI) titers of at least 1:40. Although the subjects who were older than 60 years of age also had a vigorous antibody response, there was a trend toward a better response in the intramuscular route, but this finding was significant only for antigen to the H3N2 strain. Nevertheless, 100 percent of older subjects in the intramuscular group and 93 percent of such subjects in the intradermal group had an HAI antibody titer to the H3N2 strain of more than 1:40, and 100 percent in each group had a titer of this level for both the H1N1 and B strains. Local pain was significantly more common in the intramuscular group than in the intradermal group among subjects who were 18 to 60 years of age but not among subjects who were over 60 years old. Signs of local inflammation were significantly more common among subjects in the intradermal group than among those in the intramuscular group, in both age groups. CONCLUSIONS: As compared with an intramuscular injection of full-dose influenza vaccine, an intradermal injection of a reduced dose resulted in similarly vigorous antibody responses among persons 18 to 60 years of age but not among those over the age of 60 years.

Adolescent↗
PubMedDate not supplied

A pilot study exploring mood state and dyspnea in mechanically ventilated patients.

OBJECTIVE: The objective of this study was to explore preweaning mood state and dyspnea in mechanically ventilated patients. METHODS: Before ventilatory weaning, 21 critically ill patients completed the short profile of mood states (higher scores equal greater disturbance), and a 10 cm dyspnea visual analogue scale (none to extremely severe). Weaning outcome at 24 hours was recorded. RESULTS: The mean +/- SD total mood disturbance (possible range, 0 to 16) and subscale scores (possible range, 0 to 4) were as follows: total, 6.10 +/- 4.06; tension, 1.07 +/- 0.64; depression, 1.16 +/- 0. 93; anger, 1.05 +/- 0.82; vigor, 1.04 +/- 0.84; fatigue, 1.96 +/- 0. 90; and confusion, 1.27 +/- 0.91. Mean dyspnea was 3.22 +/- 2.26 cm. Dyspnea intensity correlated negatively with vigor (r = -0.38, P <. 10). Lower preweaning vigor tended to differentiate successful from unsuccessful weaning (Mann-Whitney U = 22.0; P =.07). CONCLUSION: Patients who weaned successfully experienced greater mood disturbance. Moderate mood disturbance may be a necessary stimulus for successful weaning.

Adult↗
PubMed1975

Protection of lethally irradiated mice with allogeneic fetal liver cells: influence of irradiation dose on immunologic reconstitution.

After lethal irradiation long-lived, immunologically vigorous C3Hf mice were produced by treatment with syngeneic fetal liver cells or syngeneic newborn or adult spleen cells. Treatment of lethally irradiated mice with syngeneic or allogeneic newborn thymus cells or allogeneic newborn or adult spleen cells regularly led to fatal secondary disease or graft-versus-host reactions. Treatment of the lethally irradiated mice with fetal liver cells regularly yielded long-lived, immunologically vigorous chimeras. The introduction of the fetal liver cells into the irradiated mice appeared to be followed by development of immunological tolerance of the donor cells. The findings suggest that T-cells at an early stage of differentiation are more susceptible to tolerance induction than are T-lymphocytes at later stages of differentiation. These investigations turned up a perplexing paradox which suggests that high doses of irradiation may injure the thymic stroma, rendering it less capable of supporting certain T-cell populations in the peripheral lymphoid tissue. Alternatively, the higher and not the lower dose of irradiation may have eliminated a host cell not readily derived from fetal liver precursors which represents an important helper cell in certain cell-mediated immune functions, e.g., graft-versus-host reactions, but which is not important in others, e.g., allograft rejections. The higher dose of lethal irradiation did not permit development or maintenance of a population of spleen cells that could initiate graft-versus-host reactions but did permit the development of a population of donor cells capable of achieving vigorous allograft rejection. These observations contribute to understanding of some of the persisting immunodeficiencies that are observed in man after fatal irradiation and bone marrow transplantation. These results should suggest better approaches to more effective cellular engineering for correction of immunodeficiency diseases and for treatment of immunodeficiency diseases and of leukemias and malignancies of man.

Animals↗
PubMed1976

Experimental studies on food selective behavior in squirrel monkeys fed on riboflavin deficient diet.

The present study was conducted to determine the extent to which squirrel monkeys might demonstrate self-selective behavior when fed a riboflavin deficient diet, and the extent to which such a diet might lead to digestive disturbances, general weakness, lack of vigor, and loss of weight for such animals. Ss included 12 male squirrel monkeys approximately eight months of age. Experimental Ss, fed a riboflavin deficient diet, were tested on performance on a T-maze, a "vigor roller apparatus," and observed for digestive disturbances, general weakness, and loss of weight. Control Ss, fed a balanced diet, were given the same procedure. Significant results from the .001 to the .05 levels indicated experimental S s preferred a high riboflavin diet after the diet was deficient in this substance, and indicated digestive disturbances, lack of vigor, and loss of weight as compared with the control Ss.

Animals↗
PubMed1991

Illness, injury, and correlates of aerobic exercise and walking: a community study.

This study explores differences in exercise and walking behavior among subjects who reported temporary or long-term illnesses or injuries serious enough to have limited physical activities. The study is primarily concerned with specifying similarities and differences in correlates of vigorous exercise and walking among illness/injury groups in comparison to a healthy sample. Subjects in the analysis (N = 2,053) were drawn from a multiwave mailed survey of a probability sampling of the adult population residing in households in San Diego, California. Although differences were found in correlates of walking and vigorous exercise among the groups, self-efficacy, the belief that one is able to perform specific activities, was the most powerful and statistically significant correlate of both walking and vigorous exercise among all groups.

Adult↗
PubMed2000

Assessment of physical activity with the Computer Science and Applications, Inc., accelerometer: laboratory versus field validation.

Our purpose was to compare the validity of the Computer Science and Applications, (CSA) Inc., accelerometer in laboratory and field settings and establish CSA count ranges for light, moderate, and vigorous physical activity. Validity was determined in 60 adults during treadmill exercise, using oxygen consumption (VO2) as the criterion measure, while 30 adults walked and jogged outdoors on a 400-m track. The relationship between CSA counts and VO2 was linear (R2 = .89 SEE = 3.72 ml.kg-1.min-1), as was the relationship between velocity and counts in the field (R2 = .89, SEE = 0.89 mi.hr-1). However, significant differences were found (p < .05) between laboratory and field measures of CSA counts for light and vigorous intensity. We conclude that the CSA can be used to quantify walking and jogging outdoors on level ground; however, laboratory equations may not be appropriate for use in field settings, particularly for light and vigorous activity.

Adult↗
PubMed2002

Physical activity patterns in recent college alumni.

Within this sample of recent college alumni, a high proportion indicated that they enjoy exercise (66.1%) and felt confident in setting their own fitness programs (79.4%). Yet, only 34.3% reported engaging in recommended levels of moderate or vigorous PA. In contrast to previous reports, rates of participation in vigorous, moderate, and strengthening-type PA did not differ between men and women. Alumni who reported that they engaged in adequate levels of moderate or vigorous PA had gained significantly less weight in the years following graduation than those who reported being insufficiently active (3.0 kg vs. 6.1 kg). Last, we noted a strong positive association between PA patterns as college seniors and current PA behavior as recent alumni.

Adult↗
PubMed2002

Self-efficacy and mood in cardiac rehabilitation: should gender be considered?

The authors proposed to (a) determine the influence of phase II cardiac rehabilitation (CR) on task and barrier efficacy and mood in men and women, (b) determine the influence of task and barrier efficacy on postphase II CR exercise adherence, and (c) examine the bidirectional relationship between self-efficacy and mood. Fifty-seven men and 24 women completed task and barrier efficacy scales and the anxiety, depression, and vigor subscales 3 to 5 weeks before phase II CR, immediately before and after phase II CR, and 6 to 10 weeks after phase II CR. They found that the women had significantly larger increases in task and barrier efficacy from pre- to postphase II CR than the men did, whereas both men and women had a significant decline at follow-up. Men and women had a similar decrease in anxiety and an increase in vigor during phase II CR. However, vigor significantly declined at follow-up. All changes in mood were significantly related to changes in task and barrier efficacy.

Affect↗
PubMedDate not supplied

Preliminary studies on the effect of moderate physical activity on blood levels of glutathione.

Molecular epidemiological approaches are being used to study how physical activity may protect against cancer. Prior epidemiological data suggest that physical activity protects against lung cancer; however, interpretation of these data is complicated by potential confounding by smoking. Glutathione (GSH) detoxifies cigarette smoke carcinogens and the paper tests whether physical activity levels are associated with blood GSH levels. Study subjects were enrolled in a chemoprevention trial testing whether antioxidant micronutrient supplementation reduces genetic damage from cigarette smoking. Physical activity data were collected by questionnaire from 178 subjects at 12 months of follow-up in the trial. Total GSH (tGSH), which is the sum of free and protein-bound GSH and glutathione disulfide levels, was measured using the 5,5'-dithiobis-(2-nitrobenzenoic acid) colormetric assay with red blood cell samples collected at the 12-month time point. In multivariate linear regression analyses that controlled for gender and cigarettes smoked per day, tGSH was positively associated with hours per week of moderate intensity activity (beta=0.005, p=0.02). Hours per week of vigorous intensity activity were unassociated with tGSH and the effect of moderate activity remained after control for vigorous activity. The results are consistent with prior research showing differential effects of moderate and vigorous activity and suggest a mechanism through which physical activity may influence lung cancer risk.

Adult↗
PubMed2004

Stability and change of volume and intensity of physical activity as predictors of hypertension.

AIMS: Controversy exists concerning intensity of physical activity and risk of hypertension. Also, the association between long-term changes in physical activity and hypertension is poorly known. Therefore we investigated how the stability and change of volume and intensity of physical activity are associated with the risk of hypertension in Finnish men and women. METHODS: A total of 3,931 men and 4,381 women responded to three questionnaires on health and lifestyle. Baseline data were gathered from two questionnaires, in 1975 and 1981. The subjects were 24-51 years of age, healthy, and non-hypertensive at baseline (1981). At the end of the follow-up, in 1990, the subjects responded to a third questionnaire, according to which we assessed the cumulative incidence of hypertension between 1982 and 1990. RESULTS: The cumulative incidence of hypertension from 1982 to 1990 was 10.2% in men and 8.0% in women. In men, the risk of hypertension was higher among those who were persistently not participating in vigorous physical activity (i.e. in both 1975 and 1981) (odds ratio, 1.60; 95% confidence interval, 1.15 to 2.24; p=0.006) than among those persistently participating, when all confounding factors were adjusted for. Among those participating in vigorous activity only in 1975 or in 1981 the risk was not significantly increased compared with those participating persistently. Volume of physical activity was not associated with hypertension. In women, there was no association between physical activity and incidence of hypertension. CONCLUSIONS: Compared with inactivity, persistent vigorous physical activity predicts a low risk of hypertension in men.

Adult↗
PubMed2006

Fetal acidemia and electronic fetal heart rate patterns: is there evidence of an association?

OBJECTIVE: Despite the ubiquity of electronic fetal monitoring, the validity of the relationship between various fetal heart rate (FHR) patterns and fetal acidemia has not yet been established in a large unselected series of consecutive pregnancies. The aim of this study was to examine the published literature for evidence of such a relationship. METHODS: Four hypotheses based on assumptions in common clinical use were examined. The literature was searched for relationships between certain aspects of FHR patterns (e.g., degree of FHR variability, depth of decelerations), and fetal acidemia, or fetal vigor (5-minute Apgar score >or=7). We also attempted to relate duration of these patterns to the degree of acidemia. Using standardized FHR nomenclature we defined patterns based on baseline FHR variability, baseline rate, decelerations, and accelerations. RESULTS: The following relationships were observed: (1) Moderate FHR variability was strongly associated (98%) with an umbilical pH >7.15 or newborn vigor (5-minute Apgar score >or=7). (2) Undetectable or minimal FHR variability in the presence of late or variable decelerations was the most consistent predictor of newborn acidemia, though the association was only 23%. (3) There was a positive relationship between the degree of acidemia and the depth of decelerations or bradycardia. (4) Except for sudden profound bradycardia, newborn acidemia with decreasing FHR variability in combination with decelerations develops over a period of time approximating one hour. Most studies identified were observational and uncontrolled (grade III evidence of US Preventive Services Task Force); however, there was general agreement amongst the various studies, strengthening the validity of the observations. CONCLUSIONS: The validity of the relationship between certain FHR patterns and fetal acidemia and/or vigor, is supported by observations from the literature. In addition four assumptions commonly used in clinical management are supported. These conclusions need to be confirmed by a prospective examination of a large number of consecutive, unselected FHR patterns, and their relationship to newborn acidemia. Pending the completion of such studies, these observations can be used to justify certain aspects of current clinical management, and may assist in standardizing the diversity of opinions regarding FHR pattern management.

Acidosis↗
PubMed1994

Longitudinal analysis of T cell receptor (TCR) gene usage by human immunodeficiency virus 1 envelope-specific cytotoxic T lymphocyte clones reveals a limited TCR repertoire.

Human immunodeficiency virus 1 (HIV-1) infection is associated with a vigorous cellular immune response that allows detection of cytotoxic T lymphocyte (CTL) activity using freshly isolated peripheral blood mononuclear cells (PBMC). Although restricting class I antigens and epitopes recognized by HIV-1-specific CTL have been defined, the effector cells mediating this vigorous response have been characterized less well. Specifically, no studies have addressed the breadth and duration of response to a defined epitope. In the present study, a longitudinal analysis of T cell receptor (TCR) gene usage by CTL clones was performed in a seropositive person using TCR gene sequences as a means of tracking responses to a well-defined epitope in the glycoprotein 41 transmembrane protein. 10 CTL clones specific for this human histocompatibility leukocyte antigen-B14-restricted epitope were isolated at multiple time points over a 31-mo period. All clones were derived from a single asymptomatic HIV-1-infected individual with a vigorous response to this epitope that was detectable using unstimulated PBMC. Polymerase chain reaction amplification using V alpha and V beta family-specific primers was performed on each clone, followed by DNA sequencing of the V-D-J regions. All 10 clones utilized V alpha 14 and V beta 4 genes. Sequence analysis of the TCR revealed the first nine clones isolated to also be identical at the nucleotide level. The TCR-alpha junctional region sequence of the tenth clone was identical to the junctional region sequences of the other nine, but this clone utilized distinct D beta and J beta gene segments. This study provides evidence that the observed high degree of HIV-1-specific CTL activity may be due to monoclonal or oligoclonal expansion of specific effector cells, and that progeny of a particular CTL clone may persist for prolonged periods in vivo in the presence of a chronic productive viral infection. The observed limited TCR diversity against an immunodominant epitope may limit recognition of virus variants with mutations in regions interacting with the TCR, thereby facilitating immune escape.

Amino Acid Sequence↗