Impact of Exercise and Cognitive Stimulation Therapy on Physical Function, Cognition and Muscle Mass in Pre-Frail Older Adults in the Primary Care Setting: A Cluster Randomized Controlled Trial.

OBJECTIVES: Multicomponent exercise program have shown to improve function and cognition in older adults but studies on pre-frail older adults in the primary care setting are limited. This study aimed i) to evaluate impact of 6 months exercise (Ex) versus complementary effect of 3 months of cognitive stimulation therapy (CST) to 6 months of Ex (Ex+CST) on physical function, muscle mass and cognition versus control group at 3, 6 and 12 months ii) inflammatory biomarkers such as Interleukin-6 (IL-6) and Tumor Necrosis Factor Alpha (TNF-α). DESIGN: Cluster randomised control trial. SETTING AND INTERVENTION: Pre-frail older adults ≥ 65 years attending primary care clinic. Two intervention groups i) Ex 6 months ii) CST 3 months with Ex 6 months. MEASUREMENTS: At 0, 3, 6 and 12 months, questionnaires (on demographics, physical function, cognition, and depression) were administered and physical function assessment (gait speed, short physical performance battery (SPPB) test, handgrip strength, five times sit-to-stand (5x-STS)) was conducted. Muscle mass and its surrogates such as phase angle and body cell mass were measured using bioelectrical impedance analysis machine. Inflammatory biomarkers were measured at 0 and 3 months. RESULTS: Data from 190 participants was analysed at 3 months (111 control, 37 Ex and 41 Ex+CST). At 3 months, significant improvement in cognition was seen only in the Ex+CST group whereas improvements in depression, gait speed, SPPB and 5x-STS were seen in both the Ex and Ex+CST groups. At 6 months, the Ex+CST group improved in cognition and depression whereas improvement in frailty and muscle mass indices were seen in both the interventions groups. At 12 months, both the interventions groups had better perceived health, gait speed and less decline in muscle mass compared with control groups. Both the Ex and Ex+CST had significant association with TNF-α at 3 months (ß -2.71 (95% CI -4.80 - -0.62); p = 0.012 and ß -1.74 (95% CI -3.43 - -0.06); p = 0.043 respectively). CONCLUSION: Combined Ex+CST had significant improvement in cognition whereas the intervention groups improved in depression, physical function, muscle mass, frailty, perceived health and TNF-α levels. With growing evidence of the benefits of multicomponent interventions at primary care level, incorporating it into mainstream care with action plans on long-term sustainability and scalability should be a priority for every country.

A fast radio burst source at a complex magnetized site in a barred galaxy.

Fast radio bursts (FRBs) are highly dispersed, millisecond-duration radio bursts1-3. Recent observations of a Galactic FRB4-8 suggest that at least some FRBs originate from magnetars, but the origin of cosmological FRBs is still not settled. Here we report the detection of 1,863 bursts in 82 h over 54 days from the repeating source FRB 20201124A (ref. 9). These observations show irregular short-time variation of the Faraday rotation measure (RM), which scrutinizes the density-weighted line-of-sight magnetic field strength, of individual bursts during the first 36 days, followed by a constant RM. We detected circular polarization in more than half of the burst sample, including one burst reaching a high fractional circular polarization of 75%. Oscillations in fractional linear and circular polarizations, as well as polarization angle as a function of wavelength, were detected. All of these features provide evidence for a complicated, dynamically evolving, magnetized immediate environment within about an astronomical unit (AU; Earth-Sun distance) of the source. Our optical observations of its Milky-Way-sized, metal-rich host galaxy10-12 show a barred spiral, with the FRB source residing in a low-stellar-density interarm region at an intermediate galactocentric distance. This environment is inconsistent with a young magnetar engine formed during an extreme explosion of a massive star that resulted in a long gamma-ray burst or superluminous supernova.

Frailty and Quality of Life in Older Adults with Metabolic Syndrome - Findings from the Healthy Older People Everyday (HOPE) Study.

OBJECTIVES: Metabolic syndrome (MetS) and frailty are both associated with increased morbidity and mortality. Frailty is associated with reduced quality of life (QoL) but association of QoL with MetS have produced mixed results suggesting that other factors such as disease burden, obesity and depression may have a more significant influence. We aim to investigate the demographics of frail participants with MetS, and relationship between frailty and QoL in MetS. METHODS: Cross-sectional population study involving 292 older adults ≥ 65 years with MetS. MetS was defined using the Modified ATP III for Asians which requires the presence of 3 or more of the following 5 components 1) waist circumference ≥ 90cm for males or ≥ 80cm for females, 2) TG ≥ 150mg/dL, 3) HDLc < 40mg/dL in males or < 50mg/dL in females, 4) blood pressure ≥ 130/85mmHg or use of anti-hypertensive medication, and 5) fasting plasma glucose ≥ 100mg/dL or use of pharmacological treatment for diabetes mellitus. Data were collected on demographics, frailty (FRAIL), QoL (Euroqol-5D), perceived health, functional status, cognition, Timed-Up-and-Go (TUG), and hand-grip strength (HGS). RESULTS: 40.4% of the participants were pre-frail (MetSprefrail) and 7.2% were frail (MetSfrail). MetSfrail were significantly older, had lower education level, higher polypharmacy burden and higher prevalence of diabetes. The prevalence of at least 1 activity of daily living impairment was 4 times higher, and depression 9 times higher than their robust counterparts. MetSfrail also had longer TUG, higher prevalence of poor grip strength and poor perceived health. After adjusting for age, gender and education, MetSfrail was significantly associated with much higher odds of EQ-5D moderate to extreme problems with mobility (Odds Ratio (OR) =10.99, CI 2.62-46.14), usual activities (OR=37.82, CI 3.77-379.04) and pain (OR=10.79, CI 3.18-36.62). EQ-5D Index Value and Perceived Health improved by 0.1 (Mean Difference (MD) =0.07, CI 0.04-0.10) and 6.0 (MD=6.01, CI 3.29-8.73) respectively as frailty status improved. CONCLUSION: Frailty in MetS is associated with depression, polypharmacy, greater functional impairment, poorer QoL and perceived health. Frailty screening and personalized management is crucial in MetS as frailty may be a mediator for negative outcomes in MetS, and frailty may be reversible.

Prevalence of Anemia and Its Association with Frailty, Physical Function and Cognition in Community-Dwelling Older Adults: Findings from the HOPE Study.

OBJECTIVES: The prevalence of anemia and its impact on frailty and physical function amongst the multiethnic older populations in the Southeast Asian (SEA) countries are often not well studied. Singapore, a nation comprised of multiethnic communities, is one of the most rapidly aging population globally. We aim to evaluate the prevalence of anemia and its impact on frailty, and physical function in Healthy Older People Everyday (HOPE)- an epidemiologic population-based study on community-dwelling older adults in Singapore. DESIGN: Cross-sectional study. SETTING: Community. PARTICIPANTS: 480 adults ≥ 65 years old. MEASUREMENTS: Data were collected from interviewers-administered questionnaires on socio-demographics, FRAIL scale, Mini-Mental State Examination, EQ-5D, Barthel Index, and Lawton index. Hemoglobin concentration and physical assessments, including anthropometry, grip strength, timed up-and-go (TUG) were measured. RESULTS: The overall prevalence of anemia was 15.2% (73 out of 480). The Indian ethnic group had the highest prevalence of anemia (32%, OR=3.02; 95%CI= 1.23-7.41) with the lowest hemoglobin concentration compared to the overall population (13.0±1.3g/L and 13.5±1.4g/L, p=0.02). Hemoglobin levels and anemia were significantly associated with frailty (OR=2.28; 95% CI=1.02-5.10), low grip strength (OR=1.79; 95% CI=1.01-3.03), ≥ one IADL impairment (OR=2.35; 95% CI=1.39-3.97). Each 1 g/dL increase in hemoglobin was associated with a 6% decrease in frailty odds after adjusting for potential covariates (OR = 0.94, 95% CI: 0.90-0.99). There was a significant difference in the mean TUG between the non-anemic (11.0±3.4 seconds) and anemic (12.3±6.0 seconds, p=0.01) counterparts, but no difference in the number of falls. CONCLUSION: In our multiethnic Asian population, anemia was adversely associated with frailty, decreased muscle strength, and IADL impairment. Health policies on anemia screening should be employed to avoid or potentially delay or reverse these adverse outcomes associated with anemia. Recognition, evaluation, and treatment of anemia amongst this vulnerable population is warranted.

BMSCs attenuate hepatic fibrosis in autoimmune hepatitis through regulation of LMO7-AP1-TGFß signaling pathway.

OBJECTIVE: In a previous study, we reported that transplantation of bone mesenchymal stem cells (BMSCs) significantly attenuated liver damage in a mouse autoimmune hepatitis (AIH) model. Moreover, expression of the LIM domain protein, LMO7, correlated positively with the invasive capacity of hepatoma cells. However, whether LMO7 plays a role in inflammation and fibrosis of AIH remains unknown. This investigation aimed to explore the effect of BMSC transplantation on LMO7 and the role of LMO7 in hepatic fibrosis. MATERIALS AND METHODS: S100-induced murine AIH and LPS-induced hepatocyte injury models were successfully established. Three doses of BMSCs were injected into AIH mice via the tail vein. LPS-treated AML12 cells were co-cultured with BMSCs in vitro. Small interfering (si) LMO7 RNA and T5224 (a specific inhibitor of AP-1) were used to demonstrate the relationship between LMO7-AP1-transforming growth factor (TGF)-ß. RESULTS: Pathological examination and serum alanine and aspartate aminotransferase levels indicated that liver damage was notably ameliorated in the BMSC-treated mice. LMO7 level was upregulated, while AP-1 and TGF-ß levels were downregulated upon intervention with BMSCs. AP-1 expression was upregulated in the siLMO7 group, whereas TGF-ß level was downregulated in the T5224 group when compared to those in the control group. CONCLUSIONS: BMSC transplantation significantly limits liver fibrosis and upregulates the expression of LMO7. LMO7 inhibits the TGF-ß pathway by inhibiting AP-1. This implies that BMSCs are a potential means of treating liver fibrosis. This approach has important implications for the treatment of AIH and other fibrotic diseases.

Diverse polarization angle swings from a repeating fast radio burst source.

Fast radio bursts (FRBs) are millisecond-duration radio transients1,2 of unknown origin. Two possible mechanisms that could generate extremely coherent emission from FRBs invoke neutron star magnetospheres3-5 or relativistic shocks far from the central energy source6-8. Detailed polarization observations may help us to understand the emission mechanism. However, the available FRB polarization data have been perplexing, because they show a host of polarimetric properties, including either a constant polarization angle during each burst for some repeaters9,10 or variable polarization angles in some other apparently one-off events11,12. Here we report observations of 15 bursts from FRB 180301 and find various polarization angle swings in seven of them. The diversity of the polarization angle features of these bursts is consistent with a magnetospheric origin of the radio emission, and disfavours the radiation models invoking relativistic shocks.

Associations among menopausal status, menopausal symptoms, and depressive symptoms in midlife women in Hunan Province, China.

Objective: This study aimed to determine the associations among menopausal status, menopausal symptoms, and depressive symptoms in midlife women in Hunan, China.Methods: A secondary analysis involving 3199 women aged 40-55 years was performed based on data from the Women Health Needs Survey 2018 in Hunan Province, central south China. The depressive symptoms were determined using the 9-item Patient Health Questionnaire. The menopausal symptoms were assessed using the Kupperman Menopausal Index. Demographic characteristics and menopausal status were measured using self-administered questionnaires.Results: The prevalence of depressive symptoms was 19.3%. The three most common menopausal symptoms were insomnia (48.0%), fatigue (42.7%), and mood swing (39.8%). The increase in depressive symptoms was significantly associated with menopausal status and menopausal symptoms. After controlling for demographic variables, multivariate logistic regression showed that menopausal transition (odds ratio [OR] = 1.14, 95% confidence interval [95% CI] = 1.12-1.86), postmenopause (OR =1.52, 95% CI = 1.09-2.11), and four menopausal symptoms including mood swing (OR = 1.32, 95% CI = 1.03-1.70), depressive mood (OR = 2.28, 95% CI = 1.79-2.91), palpitations (OR = 1.37, 95% CI = 1.06-1.77), and urinary tract infection (OR = 1.49, 95% CI = 1.16-1.92) were associated with depressive symptoms.Conclusions: Independent of demographic variables, menopausal transition, postmenopause, and four menopausal symptoms (mood swing, depressive mood, palpitations, and urinary tract infection) increase the risk of depressive symptoms.

[Adenoid cystic carcinoma of external auditory canal which pain as the first symptom：a case report].

Adenoid cystic carcinoma of external auditory canal is the relatively rare malignant tumor in head and neck surgery.As the signs and symptoms of this tumour do not always correlate with the histopathologic diagnosis and subsequent clinical behavior，it is easily to be ignored. Aggressive surgical resection with adjuvant radiotherapy seems effective for local disease control.

[Related factors for severe liver fibrosis in chronic hepatitis C patients with remunerated blood donation history in Jurong of Jiangsu province].

Objective: The incidence of liver fibrosis in patients with chronic hepatitis C is high. Without effective treatment, it would lead to liver cirrhosis. This study is to identify the related factors for the incidence of liver fibrosis in patients with chronic hepatitis C in order to make early intervention treatment and reduce the case fatality rate. Methods: This cross-sectional survey was conducted in adults aged ≥50 years with local residence for more than 5 years in Jurong of Jiangsu province from March to May in 2015, the patients infected with hepatitis C virus through remunerated blood donation were screened and included in the analysis. Descriptive statistical analysis was done to compare the differences in the incidence of liver fibrosis among the patients with different age, sex and education level or co-infected with hepatitis B virus or not. The risk factors for severe liver fibrosis were identified with univariate and multivariate logistic regression analysis. Liver fibrosis was diagnosed by using FIB-4 index method. Results: A total of 719 patients with chronic hepatitis C were surveyed. Severe liver fibrosis developed in 285 of the 719 patients, in whom 21.84% was males. Multivariate logistic regression analysis showed that the patients with higher education level (OR=0.65, 95%CI: 0.47-0.90) and with access of antiviral therapy (OR=0.33, 95%CI: 0.22-0.49) had lower risk for severe liver fibrosis, the patients with high fasting blood glucose level (OR=1.80, 95% CI: 1.19-2.77) and abnormal white blood cell count (OR=2.77, 95% CI: 1.95-3.90) had higher risk for severe liver fibrosis. Conclusions: The incidence of severe liver fibrosis in patients with hepatitis C was affected by many factors. Higher education level and antiviral therapy were the protective factors, but high fasting blood glucose level and abnormal white blood cell count were the risk factors.

[Exploration of transoral robotic surgery in the treatment of pediatric obstructive sleep apnea-hypopnea syndrome].

Transoral robotic surgery (TORS) is a relatively new technique in the treatment of pediatric obstructive sleep apnea-hypopnea syndrome, which has been shown to be safe and feasible. TORS provides a minimally invasive, visualization method, which brings an unprecedented breakthrough in the treatment of pediatric obstructive sleep apnea-hypopnea syndrome. In this paper, the application and development prospect of TORS in the treatment of pediatric obstructive sleep apnea-hypopnea syndrome will be reviewed.

[HCV infection status and risk factors in remunerated blood donors in Jiangsu province].

OBJECTIVE: To investigate the infection status of HCV in remunerated blood donors and risk factors in Jiangsu province. METHODS: A Cross-sectional study was conducted among people aged >50 years. Questionnaires were used to collect the information about their demographic characteristics and risk behaviors, and venous blood samples were collected from them to detect HCV anti-body, HCV-RNA and other biochemical indicators. EpiData and Stata were used for data entry and statistical analysis. RESULTS: The overall HCV sero-prevalence rates were 22.55% and 61.05% among remunerated blood donors. Data from multiple stepwise regression analysis showed that alanine aminotransferase(ALT)(adjusted OR=1.38, 95%CI: 1.18-1.62)and aspartate aminotransferase(AST)(adjusted OR=1.30, 95%CI: 1.10-1.54)were associated with the outcomes of HCV infection, and fasting plasma glucose(adjusted OR=1.17, 95%CI: 1.01-1.35)were associated with HCV RNA viral loads. CONCLUSION: The prevalence of HCV infection in remunerated blood donors was high, clinical ALT, AST and fasting plasma glucose levels were associated with the risk for HCV infection and HCV RNA viral load.

Aetiology of genital ulcer disease in female partners of male participants in a circumcision trial in Uganda.

HIV acquisition is associated with herpes simplex virus type 2 (HSV-2) infection and genital ulcer disease (GUD). Three randomized control trials demonstrated that male circumcision significantly decreases HIV, HSV-2, human papillomavirus and self-reported GUD among men. GUD is also decreased among female partners of circumcised men, but it is unknown whether male circumcision status affects GUD pathogens in female partners. For the evaluation of GUD aetiology, two separate multiplex assays were performed to detect Haemophilus ducreyi, Treponema pallidum, HSV-1 and HSV-2. Of all the female GUD swabs evaluated, 67.5% had an aetiology identified, and HSV-2 was the primary pathogen detected (96.3%). However, there was no difference in the proportion of ulcers due to HSV-2 or other pathogens between female partners of circumcised men (11/15, 73.3%) compared with uncircumcised men (15/25, 60.0%, P = 0.39). The seroprevalence of HSV-2 is high in this population and therefore most of the detected HSV-2 infections represent reactivation. Since GUD is associated with HIV acquisition and one-third of GUD in this study did not have an aetiological agent identified, further research is needed to better understand the aetiology of GUD in Africa, and its relationship to circumcision and HIV infection.

2, 5-diketopiperazines (cyclic dipeptides) in beef: identification, synthesis, and sensory evaluation.

Stewed beef and grilled dry aged beef were analyzed as part of an in-depth analytical program, with the aim of creating new flavors incorporating only compounds identified in the target foods and identifying new synthesis targets. In-house GC-MS analyses of several types of cooked beef have identified over 1000 volatile and semivolatile components; many for the 1st time. Among the semivolatiles detected were ten 2, 5-diketopiperazines (cyclic dipeptides) previously unreported in beef. These cyclic dipeptides are cis-cyclo(L-Ile-L-Pro), cis-cyclo(L-Leu-L-Pro), cis-cyclo(L-Pro-L-Pro), cis-cyclo(L-Pro-L-Val), cis-cyclo(L-Ala-L-Pro), cyclo(Gly-L-Pro), cyclo(Gly-L-Leu), cis-cyclo(L-Met-L-Pro), cis-cyclo(L-Phe-L-Pro), and cis-cyclo(L-Phe-L-Val). All 10 cyclic dipeptides were synthesized and evaluated organoleptically. Among them cis-cyclo(L-Leu-L-Pro), cis-cyclo(L-Met-L-Pro), and cis-cyclo(L-Phe-L-Pro) were found to be of particular organoleptic interest.

A catalogue of molecular, physiological and symbiotic properties of soybean-nodulating rhizobial strains from different soybean cropping areas of China.

We have analysed 198 fast-growing soybean-nodulating rhizobial strains from four different regions of China for the following characteristics: generation time; number of plasmids; lipopolysaccharide (LPS), nodulation factors (LCOs) and PCR profiles; acidification of growth medium; capacity to grow at acid, neutral, and alkaline pH; growth on LC medium; growth at 28 and 37 degrees C; melanin production capacity; Congo red absorption and symbiotic characteristics. These unbiased analyses of a total subset of strains isolated from specific soybean-cropping areas (an approach which could be called "strainomics") can be used to answer various biological questions. We illustrate this by a comparison of the molecular characteristics of five strains with interesting symbiotic properties. From this comparison we conclude, for instance, that differences in the efficiency of nitrogen fixation or competitiveness for nodulation of these strains are not apparently related to differences in Nod factor structure.

Use of the refractometer as a tool to monitor dietary formula concentration in gastric juice.

BACKGROUND AND AIMS: Critically ill patients do not always tolerate nasogastric tube feeding. Gastric residual volumes are widely used to evaluate feeding tolerance, but controversy exists about what constitutes the residual volume (diet formula or digestive juice). In this paper, we describe the use of the refractometer as a tool to monitor dietary formula concentration in gastric juice and evaluate gastric juice refractometry as a possible clinical application. METHODS: Brix value (an index of the total solutes in solution) readings for polymeric diet at pH 1, 4, 7 and 8, and at 4 degrees C, 25 degrees C and 37 degrees C, and in fasting gastric juice were determined with a refractometer. RESULTS: We found that distilled water, minerals, and vitamins had low Brix values of 0+/-0, 1.2+/-0.1, and 0.4+/-0.1, respectively. On the other hand, because carbohydrate (17 g/100 ml), protein (5.3 g/100 ml), fat (4.1 g/100 ml), and full-strength polymeric diet had high concentrations of dissolved nutrients, they also had high Brix values (12.1+/-0.6, 6.5+/-0.1, 6.0+/-0.1, and 23.5+/-0.1, respectively). The Brix values of polymeric diet had a linear additive relationship with the diet formula concentration at various pHs, temperatures, and in the gastric juice. CONCLUSION: Brix value measurement can be used to monitor stomach dietary formula concentration. Such information can be obtained at the bedside and used to evaluate feeding-intolerant patients receiving enteral feeding.

Antinociceptive effect of astragalosides and its mechanism of action.

AIM: To study the effect and mechanism of astragalosides (AST) related to the antinociceptive activity. METHODS: The standardized formalin test was performed to induce the direct stimulation of nociceptors followed by inflammatory process in the Kunming strain mice. The involvement of opioid and nitric oxide was studied by subcutaneous injection of morphine with/without naloxone 30 min before formalin test, or peritoneal injection of L-arginine with/without L-NAME 20 min before formalin. RESULTS: AST 20, 40, and 80 mg/kg significantly lowered pain score of the second phase of formalin response as compared with control group (P<0.01). The maximum analgesic effect of AST 40 mg/kg was found at 4 h after the administration of AST (34.4 % inhibition at the second phase). Injection of morphine 5 mg/kg significantly inhibited pain response of both phases (P<0.01) and this was reversed by naloxone 2 mg/kg (P<0.01). However, naloxone did not alter the effect of AST on the second phase. Antinociceptive effect of AST 40 mg/kg was partially blocked by L-arginine 400 or 800 mg/kg (P<0.01). CONCLUSION: AST has an antinociceptive effect on formalin test in mice that is not mediated by the endogenous opioid system but related to its inhibitory effect on the production of NO.

Severe community-acquired pneumonia due to Acinetobacter baumannii.

STUDY OBJECTIVES: To investigate the clinical, epidemiologic, and microbiological characteristics of community-acquired pneumonia (CAP) due to Acinetobacter baumannii. METHODS: Retrospective chart and radiographic reviews of all patients who were admitted to National Taiwan University Hospital from January 1993 to August 1999, fulfilled the criteria for CAP, and had an isolate of A. baumannii from blood or pleural fluid at hospital admission. RESULTS: Thirteen patients (9 men and 4 women; age range, 37 to 85 years) met the criteria. Conditions associated with the infection included male gender, old age, alcoholism, malignancy, cerebrovascular disease, diabetes mellitus, renal disease, and liver cirrhosis. Eleven patients (85%) acquired the infection during the warmer months of April to October. Twelve patients (92%) had a fulminant course presenting with septic shock and respiratory failure, and 11 patients (85%) needed ventilator support and were treated in an ICU. Six patients (46%) had leukopenia. Lobar consolidations were found in 12 patients (92%), and pleural effusions were present in 4 patients (31%). All patients had positive blood culture results, two patients (15%) had positive pleural effusion culture findings, and nine patients (69%) positive sputum culture results. All the isolates were susceptible to imipenem, and most were susceptible to aminoglycosides, ceftazidime, ciprofloxacin, and extended-spectrum penicillins. Eight patients (62%) died. Four of the five survivors were initially treated with combination of a third-generation cephalosporin and an aminoglycoside. CONCLUSION: A. baumannii should be considered as a possible etiologic agent in community-acquired lobar pneumonia when (1) patients with a fulminant course present during the warmer and more humid months of the year, and (2) patients are younger alcoholics. A good sputum smear, defined as a Gram stain smear of an adequate sputum specimen that comes from the lower respiratory tract and contains > 25 leukocytes per high-power (100x) field on microscopic examination, can help early diagnosis and treatment. A combination of a third-generation cephalosporin and an aminoglycoside may be appropriate empirical therapy.

A model to study antioxidant regulation of endotoxemia-modulated neonatal granulopoiesis and granulocyte apoptosis.

Neonates with septicemia tend to develop granulocytopenia, which may, in part, be due to septic mediators such as oxygen free radicals and tumor necrosis factor alpha (TNF-alpha). Granulocytopenia may be caused by a decrease in granulocyte growth and/or an increase in granulocyte destruction. In the present study, we investigated antioxidant regulation of endotoxin-modulated neonatal granulopoiesis and granulocyte apoptosis. Using human umbilical cord blood (HUCB), we found that simulating endotoxemia in vitro elicited significant superoxide production within a few minutes. Endotoxin exposure suppressed colony-forming unit-granulocyte and monocyte formation in a dose-dependent fashion. Addition of antioxidants such as N-acetyl-cysteine could reverse the endotoxin suppression of colony-forming unit-granulocyte and monocyte formation (13 +/- 5 versus 75 +/- 5 colony-forming units/mL). Spontaneous in vitro granulocyte apoptosis in 6 h, as reflected by phosphatidylserine expression on the cell surface, was higher in granulocytes from HUCB than in those from adult blood (10.8 +/- 1.0% versus 5.6 +/- 1.2%). The addition of endotoxin or IL-8 to the cells in the in vitro model did not promote granulocyte apoptosis, but TNF-alpha, a major mediator of the effects of endotoxin, significantly induced granulocyte apoptosis in HUCB (control versus TNF-alpha: 8.9 +/- 1.2% versus 35.9 +/- 2.9%). Addition of the antioxidant N-acetyl-cysteine effectively blocked TNF-alpha-induced granulocyte apoptosis as demonstrated by DNA fragmentation. Results from these studies indicate that oxygen radicals are directly involved in endotoxin suppression of granulopoiesis, and indirectly promote granulocyte apoptosis, presumably through TNF-alpha-mediated action. Thus, under certain conditions, modulation of oxygen radical production in the blood may benefit neonates with granulocytopenia.