Impact on outcomes of measuring lactates prior to ICU in unselected heterogeneous critically ill patients: A propensity score analysis.

BACKGROUND: Elevated blood lactate levels were reported as effective predictors of clinical outcome and mortality in ICU. However, there have been no studies simply comparing the timing of measuring lactates before vs. after ICU admission. METHODS: A total of 19,226 patients with transfer time ≤ 24 hr were extracted from the Medical Information Mart for Intensive Care IV database (MIMIC-IV). After 1:1 propensity score matching, the patients were divided into two groups: measuring lactates within 3 hr before (BICU group, n = 4,755) and measuring lactate within 3 hr after ICU admission(AICU group, n = 4,755). The primary and secondary outcomes were hospital mortality, hospital 28-day mortality, ICU mortality, ICU length of stay (LOS), hospital LOS, and restricted mean survival time (RMST). RESULTS: Hospital, hospital 28-day, and ICU mortality were significantly higher in AICU group (7.0% vs.9.8%, 6.7% vs. 9.4%, and 4.6% vs.6.7%, respectively, p<0.001 for all) Hospital LOS and ICU LOS were significantly longer in AICU group (8.4 days vs. 9.0 days and 3.0 days vs. 3.5 days, respectively, p<0.001 for both). After adjustment for predefined covariates, a significant association between the timing of measuring lactate and hospital mortality was observed in inverse probability treatment weight (IPTW) multivariate regression, doubly robust multivariate regression, and multivariate regression models (OR, 0.96 [95%CI, 0.95-0.97], OR 0.52 [95%CI, 0.46-0.60], OR 0.66 [95%CI, 0.56-0.78], respectively, p<0.001 for all), indicating the timing as a significant risk-adjusted factor for lower hospital mortality. The difference (BICU-AICU) of RMST at 28- days after ICU admission was 0.531 days (95%CI, 0.002-1.059, p<0.05). Placement of A-line and PA-catheter, administration of intravenous antibiotics, and bolus fluid infusion during the first 24-hr in ICU were significantly more frequent and faster in the BICU vs AICU group (67.6% vs. 51.3% and 126min vs.197min for A-line, 19.6% vs.13.2% and 182min vs. 274min for PA-catheter, 77.5% vs.67.6% and 109min vs.168min for antibiotics, and 57.6% vs.51.6% and 224min vs.278min for bolus fluid infusion, respectively, p<0.001 for all). Additionally, a significant indirect effect was observed in frequency (0.19879 [95% CI, 0.14061-0.25697] p<0.001) and time (0.07714 [95% CI, 0.22600-0.13168], p<0.01) of A-line replacement, frequency of placement of PA-catheter (0.05614 [95% CI, 0.04088-0.07140], p<0.001) and frequency of bolus fluid infusion (0.02193 [95%CI, 0.00303-0.04083], p<0.05). CONCLUSIONS: Measuring lactates within 3 hr prior to ICU might be associated with lower hospital mortality in unselected heterogeneous critically ill patients with transfer time to ICU ≤ 24hr, presumably due to more frequent and faster therapeutic interventions.

Impact of acute mental stress on ankle blood pressure in young healthy men: a pilot study.

OBJECTIVE: Acute mental stress (MS) increases arm blood pressure (BP); however, it remains unclear whether a stress-induced pressor response is also observed in other vessels. This study aimed to examine the impact of acute MS on ankle BP. Fifty-six young, healthy men aged 19-24 years were divided into the MS (n = 29) and control (CON) (n = 27) groups; each group performed 5-min MS (mental arithmetic) or CON tasks. Systolic and diastolic BPs (SBP and DBP, respectively) of both the brachial and posterior tibial arteries were simultaneously measured at the baseline and 5 and 30 min after the task. RESULTS: In the MS group, brachial BP measures significantly increased (P < 0.05) until 30 min after the task; ankle BP measures were also significantly (P < 0.05) elevated during this time. In the CON group, no significant changes were found in brachial BP measures or ankle SBP, whereas a significant increase (P < 0.05) in ankle DBP was observed 30 min after the task. Our findings indicate that both brachial and ankle BP exhibit a sustained elevation after acute MS, suggesting a systemic pressor response by stress exposure. The measurement of ankle BP in addition to arm BP may be important to assess the stress response. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000047796 Registered on: 20th May 2022.

Acute mental stress-caused arterial stiffening can be counteracted by brief aerobic exercise.

PURPOSE: Acute mental stress (MS) causes an elevation in pulse wave velocity (PWV), an index of arterial stiffness. In contrast, aerobic exercise acutely decreases arterial stiffness, even in the short term. The present study aimed to examine whether acute MS-caused arterial stiffening can be counteracted by brief aerobic exercise. METHODS: Thirteen young healthy men (mean age, 20 ± 1 years) participated in two randomized experimental visits where they were subjected to acute MS followed by seated rest (RE) or cycling exercise (EX) trials. Following a 5-min MS task, the participants in the RE trial rested on a chair for 10 min (from 10 to 20 min after the cessation of the task), whereas those in the EX trial cycled at 35% of heart rate reserve for the same duration. Heart-brachial PWV (hbPWV), brachial-ankle PWV (baPWV), heart-ankle PWV (haPWV), and the cardio-ankle vascular index (CAVI) were simultaneously measured at baseline and 5, 30, and 45 min after the task. RESULTS: Both trials caused significant elevations (P < 0.05) in hbPWV, haPWV, and CAVI at 5 min after the task; subsequently, this persisted until 45 min after the task in the RE trial, whereas the elevations in the EX trial were eliminated. In the RE trial, baPWV significantly increased (P < 0.05) at 30 and 45 min after the task, whereas such an increase was not observed in the EX trial. CONCLUSION: The findings of the present study reveal that brief aerobic exercise counteracts arterial stiffening caused by acute MS.

Impact of acute mental stress on segmental arterial stiffness.

PURPOSE: It has been reported that acute brief episodes of mental stress (MS) result in a prolonged increase in carotid-femoral pulse wave velocity (cfPWV), an index of aortic stiffness. However, whether acute MS also impacts arterial stiffness in other segments is unclear. The present study aimed to examine the impact of acute MS on segmental arterial stiffness. METHODS: In the main experiment, 17 young male subjects (mean age, 20.1 ± 0.7 years) performed a 5-min MS and control (CON) task in a random order. Pulse wave velocity (PWV) from the heart to the brachium (hbPWV) and the ankle (haPWV), PWV between the brachial artery and the ankle (baPWV), and the cardio-ankle vascular index (CAVI) were simultaneously measured at baseline and 5, 15, and 30 min after the task. RESULTS: Compared to baseline values, hbPWV, baPWV, haPWV, and CAVI significantly increased until 30 min after the MS task, whereas these variables did not significantly change following the CON task. At 5 and 30 min after the MS task, percentage changes from baseline were significantly higher in hbPWV (+ 5.2 ± 4.4 and 6.6 ± 4.9%) than in baPWV (+ 2.2 ± 2.1 and 2.2 ± 2.0%) or haPWV (+ 3.6 ± 2.6 and 4.3 ± 2.9%) and were also significantly lower in baPWV than in haPWV. CONCLUSION: These findings suggest that acute MS elicits an increase in arterial stiffness in various segments and this arterial stiffening is not uniform among the segments.

Lactate indices as predictors of in-hospital mortality or 90-day survival after admission to an intensive care unit in unselected critically ill patients.

BACKGROUND: We performed an exclusive study to investigate the associations between a total of 23 lactate-related indices during the first 24h in an intensive care unit (ICU) and in-hospital mortality. METHODS: Nine static and 14 dynamic lactate indices, including changes in lactate concentrations (Δ Lac) and slope (linear regression coefficient), were calculated from individual critically ill patient data extracted from the Multiparameter Intelligent Monitoring for Intensive Care (MIMIC) III database. RESULTS: Data from a total of 781 ICU patients were extracted, consisted of 523 survivors and 258 non-survivors. The in-hospital mortality rate for this cohort was 33.0%. A multivariate logistic regression model identified maximal lactate concentration at 24h after ICU admission (max lactate at T24) as a significant predictor of in-hospital mortality (odds ratio = 1.431, 95% confidence interval [CI] = 1.278-1.604, p<0.001) after adjusting for predefined confounders (age, gender, sepsis, Elixhauser comorbidity score, mechanical ventilation, renal replacement therapy, vasopressors, ICU severity scores). Area under curve (AUC) for max lactate at T24 was larger (AUC = 0.776, 95% CI = 0.740-0.812) than other indices (p<0.001), comparable to an APACHE III score of 0.771. When combining max lactate at T24 with APACHE III, the AUC was increased to 0.815 (95% CI:0.783-0.847). The sensitivity, specificity, and positive and negative predictive values for the cut-off value of 3.05 mmol/L were 64.3%, 77.4%, 58.5%, and 81.5%, respectively. Kaplan-Myer survival curves of the max lactate at T24 for 90-day survival after admission to ICU demonstrated a significant difference according to the cut-off value (p<0.001). CONCLUSIONS: These data indicate that the maximal arterial lactate concentration at T24 is a robust predictor of in-hospital mortality as well as 90-day survival in unselected ICU patients with predictive ability as comparable with APACHE III score.

Skeletal Muscle Index at Intensive Care Unit Admission Is a Predictor of Intensive Care Unit-Acquired Weakness in Patients With Sepsis.

BACKGROUND: Intensive care unit-acquired weakness (ICU-AW) can be diagnosed using the Medical Research Council (MRC) score. However, such scoring may not be possible in ICU patients who may be sedated or delirious or have encephalopathy. Currently, a quantitative assessment of the cross-sectional area of the muscle is available to assess changes in skeletal muscle mass using computed tomography (CT) images. This assessment calculates the skeletal muscle index (SMI) (cm2/m2) by dividing the cross-sectional area (cm2) of the skeletal muscle at the level of the third lumbar vertebra by the square of the patient's height (m2) on CT. This study assessed the effectiveness of SMI, as measured by abdominal CT scans, in predicting the onset of ICU-AW in patients with sepsis admitted to the ICU. METHODS: We examined septic ICU patients admitted to the Niigata University Hospital ICU during 2012 - 2017 under mechanical ventilation. Patients were retrospectively divided into two groups by MRC score at ICU discharge: group AW comprised patients with an MRC score < 48, and group non-AW (NAW) comprised the remaining patients. Clinicopathological factors at ICU admission such as age, gender, underlying disease, body mass index, and SMI were compared between the two groups. Statistical analyses were performed using the Mann-Whitney U test, Fisher's exact test, receiver operator characteristic (ROC) analysis and multivariate analysis. RESULTS: A total of 31 septic patients were examined, and 23 patients met the criteria for ICU-AW. The prevalence of women was significantly higher in group AW (P < 0.05). All clinical factors, except for gender, were not significantly different between the two groups. SMI was significantly lower in group AW than in group NAW (P < 0.05). ROC analysis revealed that the cut-off value of SMI for predicting ICU-AW was 44.1, and the multivariate analysis revealed that only low SMI was a significant factor in predicting ICU-AW (P < 0.05). CONCLUSIONS: Our results show that SMI measurement at ICU admission is a valid predictive factor for ICU-AW progression in septic patients.

Early prognostication of neurological outcome by heart rate variability in adult patients with out-of-hospital sudden cardiac arrest.

BACKGROUND: Most deaths of comatose survivors of out-of-hospital sudden cardiac arrest result from withdrawal of life-sustaining treatment (WLST) decisions based on poor neurological prognostication and the family's intention. Thus, accurate prognostication is crucial to avoid premature WLST decisions. However, targeted temperature management (TTM) with sedation or neuromuscular blockade against shivering significantly affects early prognostication. In this study, we investigated whether heart rate variability (HRV) analysis could prognosticate poor neurological outcome in comatose patients undergoing hypothermic TTM. METHODS: Between January 2015 and December 2017, adult patients with out-of-hospital sudden cardiac arrest, successfully resuscitated in the emergency department and admitted to the intensive care unit of the Niigata University in Japan, were prospectively included. All patients had an initial Glasgow Coma Scale motor score of 1 and received hypothermic TTM (at 34 °C). Twenty HRV-related variables (deceleration capacity; 4 time-, 3 geometric-, and 7 frequency-domain; and 5 complexity variables) were computed based on RR intervals between 0:00 and 8:00 am within 24 h after return of spontaneous circulation (ROSC). Based on Glasgow Outcome Scale (GOS) at 2 weeks after ROSC, patients were divided into good outcome (GOS 1-2) and poor outcome (GOS 3-5) groups. RESULTS: Seventy-six patients were recruited and allocated to the good (n = 22) or poor (n = 54) outcome groups. Of the 20 HRV-related variables, ln very-low frequency (ln VLF) power, detrended fluctuation analysis (DFA) (α1), and multiscale entropy (MSE) index significantly differed between the groups (p = 0.001), with a statistically significant odds ratio (OR) by univariate logistic regression analysis (p = 0.001). Multivariate logistic regression analysis of the 3 variables identified ln VLF power and DFA (α1) as significant predictors for poor outcome (OR = 0.436, p = 0.006 and OR = 0.709, p = 0.024, respectively). The area under the receiver operating characteristic curve for ln VLF power and DFA (α1) in predicting poor outcome was 0.84 and 0.82, respectively. In addition, the minimum value of ln VLF power or DFA (α1) for the good outcome group predicted poor outcome with sensitivity = 61% and specificity = 100%. CONCLUSIONS: The present data indicate that HRV analysis could be useful for prognostication for comatose patients during hypothermic TTM.

Onset of Accelerated Muscle Deoxygenation During the 20-m Shuttle Run Test in Boys.

PURPOSE: This study aimed to compare the relative exercise intensity at which the onset of accelerated muscle deoxygenation occurs during the 20-m shuttle run test (20mSRT) between boys and men and to examine whether the timing of the onset of acceleration appearance is related to 20mSRT performance in boys. METHODS: Twenty-four boys performed the 20mSRT, during which concentration changes in oxygenated and deoxygenated hemoglobin and myoglobin (ΔOxy-Hb and ΔDeoxy-Hb, respectively) in the m. vastus lateralis were monitored using a portable near-infrared spectroscopy device. The boys' data were compared with those of 29 men in a previous study. RESULTS: An onset of accelerated decrease in Δ[Oxy-Hb - Deoxy-Hb] was found in 11 of the 24 boys (45.8%) and 20 of the 29 men (69.0%) and was found at a higher relative exercise intensity in the boys than in the men. The number of laps at which the onset of acceleration occurred correlated with total laps in the boys (r = .87). CONCLUSIONS: These findings demonstrate that the onset of accelerated muscle deoxygenation during the 20mSRT occurs at a higher relative exercise intensity in boys than in men. Our findings also show that the timing of the onset of acceleration appearance is associated with 20mSRT performance in boys.

Accelerated point of muscle deoxygenation during the 20-m shuttle run test.

This study examined whether the point of accelerated deoxygenation of active muscle occurs during the 20-m shuttle run test (20mSRT) and, if so, whether it is associated with exercise performance in the test. Twenty-nine male subjects performed the 20mSRT, and concentration changes in oxyhaemoglobin (ΔOxy-Hb) and deoxyhaemoglobin (ΔDeoxy-Hb) in the m. vastus lateralis were measured using a portable near-infrared spectroscopy device. The difference between the relative concentration changes in ΔOxy-Hb and ΔDeoxy-Hb (Δ[Oxy-Hb - Deoxy-Hb]) was regarded as the muscle oxygenation index. Group-averaged Δ[Oxy-Hb - Deoxy-Hb] showed progressive decrease during the test. However, among the individuals, we found an accelerated point of decrease in Δ[Oxy-Hb - Deoxy-Hb] in 20 subjects, which revealed that the laps at the accelerated point correlated with the total laps (r = 0·78). These results demonstrate that the accelerated deoxygenation of active muscle occurs during the 20mSRT, but not in all cases. Our findings also indicate that if the accelerated point of muscle deoxygenation occurs, the timing of its appearance is related to 20mSRT performance.

Accidental falls related to clearing heavy snow on rooftops in a rural heavy snow area in Japan.

Aim: The purpose of this study is to describe our experience with patients who fell from rooftops while clearing snow. The falls occurred in rural areas that receive heavy snowfall and are undergoing depopulation and an increasing proportion of elderly residents. Methods: A retrospective observational chart review was carried out at the sole hospital providing emergency services in a rural heavy snow area in Japan. Results: A total of 70 patients were enrolled during four winter seasons between December 2009 and March 2013. Their mean age was 61 years, and 90% were male. The mean vertical height of falls was 4.1 m. A total of 174 injuries was observed, averaging 2.5 injuries per patient. Fractures accounted for 78% of all injuries, and main fractures included vertebra with lower extremities or rib fractures; 86% of patients sustained a maximum abbreviated injury scale score of 2-3. Conclusions: In a rural heavy snow area in Japan, the incidence of accidental falls related to clearing snow was high, and the victims were elderly. Fractures accounted for 78% of all injuries, and most patients suffered from moderate to serious injuries.

A protein-protein interaction in magnetosomes: TPR protein MamA interacts with an Mms6 protein.

Magnetosomes are membrane-enveloped bacterial organelles containing nano-sized magnetic particles, and function as a cellular magnetic sensor, which assist the cells to navigate and swim along the geomagnetic field. Localized with each magnetosome is a suite of proteins involved in the synthesis, maintenance and functionalization of the organelle, however the detailed molecular organization of the proteins in magnetosomes is unresolved. MamA is one of the most abundant magnetosome-associated proteins and is anchored to the magnetosome vesicles through protein-protein interactions, but the identity of the protein that interacts with MamA is undetermined. In this study, we found that MamA binds to a magnetosome membrane protein Mms6. Two different molecular masses of Mms6, 14.5-kDa and 6.0-kDa, were associated with the magnetosomes. Using affinity chromatography, we identified that the 14.5-kDa Mms6 interacts with MamA, and the interaction was further confirmed by pull-down, immunoprecipitation and size-exclusion chromatography assays. Prior to this, Mms6 was assumed to be strictly involved with biomineralizing magnetite; however, these results suggest that Mms6 has an additional responsibility, binding to MamA.

A novel mitochondrial nuclease-associated protein: a major executor of the programmed nuclear death in Tetrahymena thermophila.

BACKGROUND INFORMATION: Programmed nuclear death (PND) in the ciliate Tetrahymena is an apoptosis-like phenomenon that occurs in a restricted space of cytoplasm during conjugation. In the process, only the parental macronucleus is selectively eliminated from the progeny cytoplasm, in conjunction with differentiation of new macronuclei for the next generation. For the last decade, mitochondria have been elucidated to be a crucial executioner like apoptosis: apoptosis-inducing factor and yet-unidentified nucleases localised in mitochondria are major factors for PND. RESULTS: To identify such nucleases, we performed a DNase assay in a PAGE (SDS-DNA-PAGE) using total mitochondrial proteins. Some proteins showed DNase activity, but particularly a 17 kDa protein exhibited the highest and predominant activity. Mass spectrometric analysis revealed a novel mitochondrial nuclease, named TMN1, whose homologue has been discovered only in the ciliate Paramecium tetraurelia, but not in other eukaryotes. Gene disruption of TMN1 led to a drastic reduction of mitochondrial nuclease activity and blocked nuclear degradation during conjugation, but did not affect accumulation of autophagic and lysosomal machinery around the parental macronucleus. CONCLUSIONS: These observations strongly suggest that the mitochondrial nuclease-associated protein plays a key role in PND as a major executor. Taking the novel protein specific to ciliates in consideration, Tetrahymena would have diverted a different protein from common apoptotic factors shared in eukaryotes to PND in the course of ciliate evolution.

Effective delayed percutaneous coronary intervention for advanced atrial ventricular block in patients with recent myocardial infarction.

We present a case of effective late reperfusion for atrio-ventricular conduction recovery in a patient with recent myocardial infarction complicated by advanced atrio-ventricular block (AVB). A 50-year-old Japanese man was transferred to our hospital with a recent diagnosis of myocardial infarction 44 h after onset. We performed emergent coronary angiography on Day 5 because he developed bradycardia with two to one advanced AVB resistant to atropine without chest pain or ST-T changes. Coronary angiography showed the right coronary artery (RCA) with total proximal occlusion. Emergent percutaneous coronary intervention (PCI) was performed to the RCA. Just after PCI, the PR interval was shortened to 0.25 s. Moreover, the PR interval was shortened to 0.18 s at Day 16. This report shows the new finding that delayed PCI may be effective in patients with recent myocardial infarction complicated by new AVB outside of the usual therapeutic window of 12 h.

Clinical and cardiac features of patients with subarachnoid haemorrhage presenting with out-of-hospital cardiac arrest.

BACKGROUND: Subarachnoid haemorrhage (SAH) is known as one of the aetiologies of out-of-hospital cardiac arrest (OHCA). However, the mechanisms of circulatory collapse in these patients have remained unclear. METHODS AND RESULTS: We examined 244 consecutive OHCA patients transferred to our emergency department. Head computed tomography was performed on all patients and revealed the existence of SAH in 14 patients (5.9%, 10 females). Among these, sudden collapse was witnessed in 7 patients (50%). On their initial cardiac rhythm, all 14 patients showed asystole or pulseless electrical activity, but no ventricular fibrillation (VF). Return of spontaneous circulation (ROSC) was obtained in 10 of the 14 patients (14.9% of all ROSC patients) although all resuscitated patients died later. The ROSC rate in patients with SAH (71%) was significantly higher than that of patients with either other types of intracranial haemorrhage (25%, n=2/8) or presumed cardiovascular aetiologies (22%, n=23/101) (p<0.01). On electrocardiograms, ST-T abnormalities and/or QT prolongation were found in all 10 resuscitated patients. Despite their electrocardiographic abnormalities, only 3 patients showed echocardiographic abnormalities. CONCLUSIONS: The frequency of SAH in patients with all causes of OHCA was about 6%, and in resuscitated patients was about 15%. The initial cardiac rhythm revealed no VF even though half had a witnessed arrest. A high ROSC rate was observed in patients with SAH, although none survived to hospital discharge.

Transient left ventricular apical ballooning in a patient with cardiac arrest after subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) often accompanies cardiac abnormalities. Sudden cardiac arrest is also known to occur after SAH. A 32-year-old woman was admitted to our hospital because of cardiac arrest immediately after the onset of SAH. Return of spontaneous circulation was obtained by conventional advanced cardiovascular life support. After resuscitation, her echocardiogram showed left ventricular apical ballooning, which improved within 7 days. This is the first report presenting both sudden cardiac arrest and transient left ventricular apical ballooning after SAH.

Prompt prediction of successful defibrillation from 1-s ventricular fibrillation waveform in patients with out-of-hospital sudden cardiac arrest.

PURPOSE: Ventricular fibrillation (VF) is a common cardiac arrest rhythm that can be terminated by electrical defibrillation. During cardiopulmonary resuscitation, there is a strong need for a prompt and reliable predictor of successful defibrillation because myocardial damage can result from repeated futile defibrillation attempts. Continuous wavelet transform (CWT) provides excellent time and frequency resolution of signals. The purpose of this study was to evaluate whether features based on CWT could predict successful defibrillation. METHODS: VF electrocardiogram (ECG) waveforms stored in ambulance-located defibrillators were collected. Predefibrillation waveforms were divided into 1.0- or 5.12-s VF waveforms. Indices in frequency domain or nonlinear analysis were calculated on the 5.12-s waveform. Simultaneously, CWT was performed on the 1.0-s waveform, and total low-band (1-3 Hz), mid-band (3-10 Hz), and high-band (10-32 Hz) energy were calculated. RESULTS: In 152 patients with out-of-hospital cardiac arrest, a total of 233 ECG predefibrillation recordings, consisting of 164 unsuccessful and 69 successful episodes, were analyzed. Indices of frequency domain analysis (peak frequency, centroid frequency, and amplitude spectral area), nonlinear analysis (approximate entropy and Hurst exponent, detrended fluctuation analysis), and CWT analysis (mid-band and high-band energy) were significantly different between unsuccessful and successful episodes (P < 0.01 for all). However, logistic regression analysis showed that centroid frequency and total mid-band energy were effective predictors (P < 0.01 for both). CONCLUSIONS: Energy spectrum analysis based on CWT as short as a 1.0-s VF ECG waveform enables prompt and reliable prediction of successful defibrillation.

Gigantic macroautophagy in programmed nuclear death of Tetrahymena thermophila.

Programmed nuclear death (PND) in Tetrahymena is a unique process during conjugation, in which only the parental macronucleus is degraded and then eliminated from the progeny cytoplasm, but other co-existing nuclei such as new micro- and macronuclei are unaffected. PND through autophagic elimination is expected to be strictly controlled, considering the significant roles in ciliates such as turnover of disused organelles and production of the next generation. Here we demonstrate that PND in Tetrahymena involves peculiar aspects of autophagy, which differ from mammalian or yeast macroautophagy. Drastic change of the parental macronucleus occurs when differentiation of new macronuclei is initiated. Combined use of monodansylcadaverine and a lysosome indicator LysoTracker Red showed that prior to nuclear condensation, the envelope of the parental macronucleus changed its nature as if it is an autophagic membrane, without the accumulation of a pre-autophagosomal structure from the cytoplasm. Subsequently, lysosomes approached only to the parental macronucleus and localized at the envelope until a final resorption stage. In addition, we found that the parental macronucleus exhibits certain sugars and phosphatidylserine on the envelope, which are possible "attack me" signals, that are not found on other types of nuclei. These findings suggest that PND is a highly elaborated process, different from the typical macroautophagy seen in other systems, and is executed through interaction between specific molecular signals on the parental macronuclear envelope and autophagic/lysosomal machineries.

Arterial oxygen desaturation response to repeated bouts of sprint exercise in healthy young women.

The decline in arterial oxygen saturation of hemoglobin during exercise has been termed exercise-induced arterial hypoxemia (EIAH). We examined whether repeated bouts of sprint exercise (SprE) would induce EIAH in healthy young men and women. Ten men and 11 women (20.4 +/- 0.3 year) performed an anaerobic power test (three bouts of 10 s cycling with 120 s intervals) using a cycle ergometer. Arterial oxygen saturation of hemoglobin measured by pulse oximeter (SpO(2)), heart rate (HR), rate perceived exertion (RPE), and the blood lactate concentration ([La](b)) were assessed at rest, during, and 5 min after repeated bouts of SprE. Women exhibited a lower maximal anaerobic power (MAnP) compared to men (498 +/- 23 vs. 759 +/- 22 watts, respectively, p < 0.01). HR, RPE, and [La](b) in women were comparable with those in men throughout the test. However, the only significant decline in SpO(2) after a single bout of SprE (95.5 +/- 0.7%) from the resting value (97.9 +/- 0.2%) was observed in women, and further declines occurred following heavier SprE (< 95%). In 8 of 11 women, mild to moderate EIAH developed, whereas only 2 men showed mild EIAH. Thus, these findings suggest that repeated bouts of SprE might induce mild EIAH in young women but not men.