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Scalp hypothermia to prevent chemotherapy-induced alopecia is effective and safe: a pilot study of a new digitized scalp-cooling system used in 74 patients.

GOALS: The aim of this study was to examine the efficacy and safety of a new digitized, controlled, scalp-cooling system to prevent chemotherapy-induced alopecia. METHOD: Seventy-four female cancer patients who received 13 varying chemotherapy regimens were included in a nonrandomized pilot study. The Digni 2-3 with Dignicap system consists of a refrigerator unit and a control unit integrated into a mobile cabinet and connected to a tight-fitting cooling cap. This system maintains a constant scalp temperature of +5 degrees C for many hours. In this study, 60 patients were treated for ovarian cancer with either taxane or epirubicin combination chemotherapy. Eight patients with Hodgkin's lymphoma, three with breast cancer, two with endometrial cancer, and one with sarcoma were also included. Photo documentation and patient assessment of hair loss and discomfort were performed. RESULTS: In anthracycline-treated patients, total prevention of hair loss was observed, whereas hair loss in paclitaxel/docetaxel-treated patients was minimal to none. The combination of anthracycline and taxane resulted in more hair loss, but only three of six patients used a wig. Scalp cooling was generally very well tolerated; only two of 74 patients discontinued use of the cold cap due to discomfort. No scalp metastases occurred over a median follow-up period of 15 months. CONCLUSIONS: The digitized, controlled, scalp-cooling system represents an effective and safe device that should be clinically evaluated in a randomized trial and in studies using other chemotherapy regimens to determine optimal temperatures and durations of cooling for maximal efficacy.

Adult↗

Effects of ethanol on thermoregulation.

Clinical reports of accidental hypothermia in alcohol intoxicated individuals exposed to low ambient temperature ( Paton , 1983) have generally been borne out by experimental studies in healthy volunteers. Small doses of ethanol, given to human subjects at normal ambient temperature (Ta), have very little effect on body temperature but a combination of large dose, low Ta and vasodilatation provoked by strenuous exercise, causes a sharp fall in rectal temperature. In experimental animals, the use of relatively larger doses of alcohol and more extreme temperatures, both above and below the thermoneutral zone, has shown that the effect of ethanol is essentially poikilothermic, i.e. an impairment of adaptation to both heat and cold. This effect has been studied in greater detail, in relation to each of the basic thermoregulatory processes. Though small doses of alcohol may increase the metabolic rate under some circumstances, the most common effect at low Ta is inhibition of shivering and therefore reduction of thermogenesis. At the same time it tends to cause increased heat loss by cutaneous vasodilatation. This makes for a greater feeling of comfort in the cold exposed subjects but increases in rate of fall of core temperature. The combination of decreased thermogenesis and increased heat loss, despite falling body temperature, is suggestive of a lowering of the set-point of the thermoregulatory control mechanisms. Consistent with this is a slight increase in ventilatory heat loss after low doses of ethanol but larger doses cause respiratory depression, so that heat loss through the lungs is minor. However, at high Ta ethanol caused hyperthermia in experimental animals and shows enhanced lethality, so that impairment of thermoregulatory effector mechanisms seems to be at least as important as change in set-point. Studies of the effects of ethanol on electrophysiological activity of single neurons in the pre-optic area and anterior hypothalamus (POAH), biochemical activities of neuronal membranes, hypothalamic blood flow, conventional neurotransmitters, amino acid putative neurotransmitters, neuropeptides, prostaglandins and inorganic ions have all failed so far to yield a clear comprehensive picture of the mechanisms by which ethanol affects thermoregulation. In each case, contradictory evidence has been obtained concerning the consequences of ethanol administration, whether by oral, intraperitoneal, intravenous, intracerebroventricular, or direct local (POAH) route.(ABSTRACT TRUNCATED AT 400 WORDS)

Alcoholism↗

The high-affinity cAMP phosphodiesterase of Saccharomyces cerevisiae is the major determinant of cAMP levels in stationary phase: involvement of different branches of the Ras-cyclic AMP pathway in stress responses.

The Ras-cyclic AMP (cAMP) pathway is a major determinant of intrinsic stress resistance of the yeast Saccharomyces cerevisiae. Here, we isolated IRA2, encoding the Ras GTPase activator, as a global stress response gene. Subsequently, we studied the other negative regulators on the separate branch of the Ras-cAMP pathway, the low- or high-affinity cAMP phosphodiesterase encoded by PDE1 or PDE2, respectively. Deletion of PDE2, similar to ira2 deletion, rendered cells sensitive to freeze-thawing, peroxides, paraquat, cycloheximide, heavy metals, NaCl, heat, or cold shock. However, deletion of PDE1 did not affect stress tolerance, although it exacerbated stress sensitivity caused by the pde2 deletion, indicating that PDE1 can partly compensate for PDE2. Deletion of IRA2 uniquely led to high sensitivity to cumene hydroperoxide, suggesting that IRA2 may have a distinct role for the response to this stress. Stress sensitivity of yeast cells in general correlated with the basal level of cAMP. Interestingly, yeast cells lacking PDE2 maintained higher cAMP levels in stationary phase than exponential growth phase, suggesting that Pde2p is the major regulator of cAMP levels in stationary phase. Depletion of Ras activity could not effectively suppress stress sensitivity caused by lack of cAMP phosphodiesterases although it could suppress stress sensitivity caused by lack of IRA2, indicating that cAMP accumulation in stationary phase can be mediated by other signaling proteins in addition to Ras. Our study shows that control of cAMP basal levels is important for determining intrinsic stress tolerance of yeast, and that the cAMP level during stationary phase is a result of a dynamic balance between its rates of synthesis and degradation.

3',5'-Cyclic-AMP Phosphodiesterases↗

Cold air inhalation and exercise-induced bronchoconstriction in relationship to metacholine bronchial responsiveness: different patterns in asthmatic children and children with other chronic lung diseases.

Cold air inhalation and exercise-induced bronchoconstriction (EIB) have both been used as measures of bronchial responsiveness. Both stimuli are often combined in the Nordic climate. The main objective of the present study was to investigate the climatic influence of cold temperatures upon exercise-induced asthma. The secondary aims were: (a) to assess metacholine bronchial hyper-responsiveness and EIB in children with bronchial asthma (n = 32; mean age 10.8 years) compared to children with other chronic lung diseases (CLD) (n = 26, mean age 10.1 years); and (b) to assess the influence of cold air inhalation upon EIB in the two groups of children. Methods used were: (a) the metacholine concentration causing a reduction in FEV1 of 20% (PC20-M), (b) maximum FEV1 fall (delta FEV1) after submaximal treadmill run (EIB test); and (c) delta FEV1 after submaximal treadmill run while inhaling cold (-20 degrees C) dry air (CA-EIB test). Geometric mean PC20-M did not differ significantly between the asthma children (1.28 mg ml-1) and the CLD children (2.90 mg ml-1). In the asthma children, mean delta FEV1 after EIB test was 12.8% vs 21.8% after adding cold air (P < 0.0001), compared to 5.2 and 7.4%, respectively (P = 0.03), in the CLD group. Maximum sensitivity and specificity for the EIB test were 69.8% at a fall in FEV1 of 6.8%; for the CA-EIB test, 72% at a fall in FEV1 of 10.2%; and for metacholine provocation, 56% at a PC20-M of 1.5 mg ml-1. In conclusion, children with bronchial asthma are substantially more sensitive to cold air than children with CLD, and EIB is markedly increased by cold air inhalation in asthmatic children, maintaining the specificity of the EIB test and increasing the sensitivity. The low sensitivity of the EIB test is probably influenced by the use of inhaled steroids. Metacholine inhalation test has less specificity and sensitivity in discriminating asthma from other chronic lung diseases.

Asthma, Exercise-Induced↗

Determinants of endurance exercise capacity in the heat in prepubertal boys.

The goal of this study was to identify factors which limit exercise endurance in hot ambient conditions in prepubertal boys. Eight healthy non-acclimatized, highly physically active prepubertal boys performed steady load cycling at approximately 65 % peak VO (2) to exhaustion in both cool (19.6 +/- 0.6 degrees C, 66.4 +/- 11.0 % relative humidity) and hot (31.0 +/- 0.3 degrees C, 56.9 +/- 2.0 % relative humidity) environmental conditions. Cardiac output, oxygen uptake, rectal temperature (T (re)), rating of perceived exertion (RPE), blood pressure, and calculated arterial venous oxygen difference were obtained serially in each testing session, and percent dehydration was calculated from body weight loss. Endurance time was significantly shorter in the hot condition (29.30 +/- 6.19 minutes versus 41.38 +/- 6.30 minutes in the cool room). No significant differences in circulatory markers or hydration status were observed either during testing or between cycling thermal conditions. Rate of rise of T (re) was greater during exercise in the heat, but no significant difference in T (re) between conditions was observed at exhaustion. Mean values of RPE were consistently greater during exercise in the heat, but these differences did not reach statistical significance. These findings support the concept that rises in core temperature and/or brain perception (RPE) rather than circulatory insufficiency may be the critical factors defining limits to exercise in the heat.

Blood Pressure↗

Exercise in the cold.

Exercising in the cold is not an attractive option for many athletes; however, defining what represents cold is difficult and is not standard for all events. If the exercise is prolonged and undertaken at a moderate intensity, environmental temperatures around 11 degrees C can be an advantage. If the intensity is lower than this value and the individual does not generate sufficient metabolic heat to offset the effects imposed by the cold environment, then temperatures of 11 degrees C can be detrimental to performance. Similarly, when the performance involves dynamic explosive contractions, then a Cold ambient temperature can have a negative influence. Additional factors such as the exercising medium, air or water, and the anthropometric characteristics of the athlete will also make a difference to the strategies that can be adopted to offset any negative impact of a cold environment on performance. To plan for a performance in the cold requires an understanding of the mechanisms underpinning the physiological response. This review attempts to outline these mechanisms and how they can be manipulated to optimize performance.

Acclimatization↗

The chromosome-level genome of Stylosanthes guianensis provides insights into genome evolution and environmental adaptation.

Stylosanthes guianensis is a leguminous forage crop of significant economic importance, primarily distributed in tropical and subtropical regions. It exhibits strong adaptability to various stresses, yet the genetic basis underlying this trait remains unclear. In this study, we constructed the first chromosome-scale reference genome of S. guianensis using a combination of Nanopore and Hi-C sequencing technologies. The assembled genome size is 1254&#x2009;Mb, with 10 pseudochromosomes. Using Nanopore full-length transcriptome data, we generated high-quality transcript-level gene annotations, identifying 36&#x2009;585 gene models and 110&#x2009;601 transcripts. The repetitive sequences in S. guianensis account for 79.16% of the genome, with the extensive expansion of Gypsy elements in long terminal repeats contributing to its genome size enlargement. Comparative genomic and transcriptomic analyses revealed that flavonoid metabolism plays a pivotal role in stress adaptation, providing new insights into the genetic basis of stress tolerance. Additionally, we generated whole-genome methylation profiles under cold treatment and control conditions, offering valuable data for future epigenomic research. These findings provide essential molecular resources for understanding stress resilience in S. guianensis and advancing its molecular breeding.

Genome, Plant↗

Physiological determinants of hyperreactivity to stress in borderline hypertension.

Blood pressure hyperreactivity during stress is characteristic of borderline hypertension in white men. The present study evaluated the hemodynamic basis of this hyperreactivity and assessed its physiological basis in terms of sympathetic nervous system function. Cardiovascular adjustments to an aversive reaction time test were compared with those of the forehead cold pressor test, representing stressors that elicit active behavioral responses in contrast to passive tolerance of aversive stimulation. As anticipated, blood pressure increases were greater in 12 borderline hypertensive men compared with 21 age-matched normotensive men during the active reaction time stressor but not during the passive cold pressor test. The pressor hyperreactivity in borderline hypertensives was associated with excessive rises in plasma epinephrine and norepinephrine, leading to greater increases in cardiac output, despite evidence that the cardiac beta-adrenergic receptors in these subjects were downregulated compared with those of normotensive subjects. During the cold pressor test, borderline hypertension was associated with greater increases in systemic vascular resistance, which, in the presence of normal baroreceptor reflex function, led to an attenuation of cardiac output, thus producing no greater net effect on blood pressure than seen in normotensive subjects. Evidence of vascular hypertrophy in the borderline hypertensive subjects was considered to account for their vascular hyperreactivity to cold pressor stimulation. Collectively, the observations in this study further support the view that the early stages of hypertension in white men are characterized by sympathetic nervous system hyperreactivity, but only in association with tasks that elicit active behavioral coping responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗

Genetic Analysis of Genomic and Methylomic Variation and Identification of Multi-Trait Mutants in Rice Carried on Chang'e-5.

Global food security is facing challenges from population growth to diminishing arable land. Space mutation breeding holds promise for overcoming the variation limitations in conventional breeding; however, the mutagenic effects of the deep-space environment on rice and the transgenerational inheritance patterns of induced variations remain unclear. In this study, rice seeds carried by the Chang'e-5 spacecraft were used as materials. Whole-genome sequencing and whole-genome bisulfite sequencing were performed on the first (SP1) and second generations (SP2) of space-mutagenized plants after their return to Earth. The results showed that the number of genomic variants in the SP2 generation increased significantly compared with SP1, and SNPs, homozygous sites, and variants in coding regions were more heritable. The genome-wide methylation level was elevated in the SP2 generation, and among differentially methylated cytosines, those in the CG context exhibited the highest heritability. Furthermore, large-scale screening for nitrogen efficiency, tolerance to PEG-induced stress, and germination-stage cold resistant mutants was conducted in the SP2 generation, and phenotypic validation was performed in the third generation (SP3). By integrating multi-omics analyses of representative mutants to mine candidate genes, a number of heritable elite mutants were obtained, and seven candidate genes for key traits were identified. This study systematically elucidates the transgenerational inheritance patterns of deep-space-induced variation in rice. The multi-trait mutants obtained provide valuable germplasm resources for gene cloning and breeding applications in rice.

DNA methylation↗

Cold temperature impairs maximal exercise performance in patients with heart failure: attenuation by acute ACE inhibitor therapy.

BACKGROUND: Cold exposure decreases ischemic threshold in patients with coronary artery disease and preserved left ventricle (LV) function. The impact of cold exposure and the effect of acute angiotensin-converting enzyme (ACE) inhibitor therapy on maximal exercise capacity have not been studied in patients with symptomatic congestive heart failure. METHODS AND RESULTS: Eleven patients with New York Heart Association class II and III congestive heart failure, aged 61 6 years (mean SD), with LV ejection fraction 25 6%, completed four symptoms-limited maximal exercise tests at 20 C and -8 C in a cold chamber. The exercise tests were performed while the patients were treated with lisinopril for three days, or a placebo. Cold exposure significantly decreased exercise duration in patients treated with a placebo (506 156 s [20 C] versus 419 182 s [-8 C], P<0.01). Rate-pressure products measured at 4 min during the test and at peak performance were significantly increased at -8 C. Patients treated with lisinopril exhibited a significant attenuation of the decrease in exercise time in the cold (-17% for placebo versus -6.6% for lisinopril, P<0.05). CONCLUSIONS: Cold temperature increases cardiac demand in response to exercise and significantly reduces maximal exercise capacity in patients with symptomatic heart failure. Acute treatment with lisinopril attenuates the impact of cold on exercise capacity.

Angiotensin-Converting Enzyme Inhibitors↗

[Occurrence of Yersinia enterocolitica, particularly serovar 03, biovar 4 in pork and beef].

The paper deals with the incidence of Yersiniae in pork and beef, focused in particular on the prevalence of Yersinia enterocolitica, serovar 3, biovar 4. The author uses for detection the method of cold shock, alkalization of the sample, taking advantage of the tolerance of Yersinias of diluted alkalis and suppressing the contaminating microflora, and the the selective medium CIN agar with a locally manufactured supplement. Cultivation was either direct or after propagation in phosphate buffer pH 7.6. The authors isolated 84 strains of Yersinias, i.e. 60% of the total number of examined specimens. Four strains were Yersinia enterocolitica, serovar 03, biovar 4 from pork by direct cultivation. Twenty strains did not agglutinate with commercial serum O-Yersinia IMUNA; they were included in the group "Yersinia enterocolitica other biovars" and 60 strains were "Environmental Yersinia isolates". The author proved a seasonal incidence of Yersinie enterocolitica, serovar 03, biovar 4. The applied method of detection and the the selective medium CIN agar with supplement proved suitable. It is important to respect hygienic provisions during processing in the slaughterhouse with regard to the high incidence of environmental Yersinias and the possible incidence of pathogenic serovars of Yersinias.

Animals↗

Outpatient cervical conization with the CO2 laser.

Ninety-six patients with grade 3 cervical intraepithelial neoplasia (CIN) were treated with CO2 laser conization, and 45 were treated with cold-knife conization. Local anesthesia was used in 83% of the patients in the laser group; the rest received general anesthesia. In the laser group seven patients developed peri- and postoperative hemorrhages. Hemorrhages occurred among four of those treated with cold-knife conization. Laser conization with local anesthesia was well tolerated and can be recommended as an outpatient procedure for patients with endocervical grade 3 CIN or lesions suggestive of microinvasive cancer.

Adult↗

Diclofenac does not interact with codeine metabolism in vivo: a study in healthy volunteers.

BACKGROUND: Previously, we have demonstrated a marked inhibition of codeine glucuronidation by diclofenac in human liver tissue homogenate. We therefore aimed to investigate whether diclofenac inhibits glucuronidation of codeine also in vivo in healthy volunteers. METHODS: In a randomised, placebo-controlled, double-blind, cross-over study, 12 healthy volunteers received a singe of 100 mg codeine phosphate plus 50 mg diclofenac sodium or codeine phosphate plus placebo. Over a 36 hour period serum concentrations of codeine and its metabolites as well as urinary excretion were analysed using LC-mass spectrometry. Side effects were recorded and analgesic efficacy was determined using the cold pressor test (0-6 h). RESULTS: A single dose of diclofenac did not alter the formation of codeine-6-glucuronide in healthy volunteers. Metabolic clearance of codeine to morphine was not affected by diclofenac. In terms of side effects, both treatments were well tolerated. Diclofenac did not significantly influence the analgesic effects of codeine in the cold pressor test. CONCLUSIONS: In contrast to recent in vitro data, a single oral dose of diclofenac did not alter the glucuronidation of codeine in healthy volunteers.

Adult↗