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The effect of birthplace on heat tolerance and mortality in Milan, Italy, 1980-1989.

The temperature-mortality relationship follows a well-known J-V shaped pattern with mortality excesses recorded at cold and hot temperatures, and minimum at some optimal value, referred as Minimum Mortality Temperature (MMT). As the MMT, which is used to measure the population heat-tolerance, is higher for people living in warmer places, it has been argued that populations will adapt to temperature changes. We tested this notion by taking advantage of a huge migratory flow that occurred in Italy during the 1950s, when a large number of unemployed people moved from the southern to the industrializing north-western regions. We have analyzed mortality-temperature relationships in Milan residents, split by groups identified by area of birth. In order to obtain estimates of the temperature-related risks, log-linear models have been used to fit daily death count data as a function of different explanatory variables. Results suggest that mortality risks differ by birthplace, regardless of the place of residence, namely heat tolerance in adult life could be modulated by outdoor temperature experienced early in life. This indicates that no complete adaptation might occur with rising external environmental temperatures.

Hot Temperature↗

Human pain responsivity in a tonic pain model: psychological determinants.

Human pain responsivity was defined as the subject's behavioral pain endurance time (PET) to the 1 +/- 0.3 degrees C cold-pressor test, a naturalistic and clinical analogue tonic pain model. Over the past 2 years, we have consistently observed a behavioral dichotomy of pain responsivity in each of our 6 studies (all at P less than 0.000001 effect level), totaling 205 subjects. Overall, the pain-tolerant (PT) subjects could endure the whole 5 min (note that 3 min was the ceiling criterion in the last study) of cold-pressor test, while the pain-sensitive (PS) subjects could merely tolerate the test for an overall mean of 60 sec, 20% of PET in the PT group. No overlapping of distribution was observed between these 2 populations. Further, we observed that the percentage of subjects in each of these 2 groups varied substantially across studies. The mean pain perception (Visual Analogue Scale) of tonic pain ranged from 60-70 for both aversiveness and intensity scales. The characteristics of this tonic pain, assessed by the McGill Pain Questionnaire (MPQ), showed similar patterns across each study with a high degree of consistency. Although ratings of pain aversiveness did not differ in the PT vs. PS subjects, ratings of pain intensity did differ, with the PT subject reporting less pain. It was found that state anxiety correlated with MPQ scores for PS, but not PT, subjects. Additionally, psychological tests (Tellegen Absorbance Scale, Kleinknecht Fear, Spielberger Trait-Anxiety) were positively correlated with certain MPQ measures for PS, but not PT subjects. Multivariate regression analyses indicated, in the PS but not the PT group, that 36% of variance in pain score (MPQ-T) could be predicted by the psychological trait factors. The general level of fear contributed singularly as the major predictor variable in the pain-sensitive individuals. We consider this tonic pain model indeed offers a succinct empirical paradigm to study human pain responsivity in general. The psychological/physiological etiology of such drastic human pain responsivity requires intense systematic investigations. This report discusses the results in: (a) individual differences in pain responsivity, (b) characterization of the cold-pressor test as a model for tonic pain, (c) contrast between PS and PT groups of pain perception and state anxiety, and (d) psychological determinants of measures for cognitive, perceptual and affective domains. Discussion was also focused on the experimental tonic pain model and its generality for clinical pain, as well as the basic model of the cold-pressor test for human tonic pain responsivity.

Adolescent↗

Personality factors in the explanation of sex differences in pain catastrophizing and response to experimental pain.

OBJECTIVE: To examine the effects of personality and pain catastrophizing upon pain tolerance and pain ratings and to examine the impact of an experimental pain induction on subsequent ratings of catastrophizing. METHOD: Two hundred nineteen college students participated in a cold pressor task. Sex-differentiating personality constructs were measured by the Extended Personal Attributes Questionnaire. The Pain Catastrophizing Scale was given before and after the cold pressor task. RESULTS: A path-analytic model fit the data well and permitted tests of explanatory relationships. Mediational analyses demonstrated that sex differences in catastrophizing were explained by the Personal Attributes Questionnaire Masculinity-Femininity and Verbal Passive-Aggressiveness scales. Pain tolerance and pain ratings differed significantly between men and women, but Masculinity-Femininity partially mediated those sex-pain relationships. Additionally, higher pain ratings and lower pain tolerance were independently associated with increased catastrophizing after the cold pressor task. CONCLUSIONS: The results suggest that sex differences in catastrophizing and pain responsivity are partially accounted for by the dispositional tendency to describe oneself as emotionally vulnerable. The findings also suggest that pain catastrophizing may be situational as well as dispositional.

Adolescent↗

The physical and psychological experience of pain: the effects of labeling and cold pressor temperature on three pain measures in college women.

Using the cold pressor test, three experiments were conducted to investigate the effects of water temperature and labeling on three dependent measures in college women: behavioral pain tolerance (BPT), a sensory rating of the pain experience (SR) and a parallel affective rating of the experience (AR). Temperature of the cold pressor was varied as the physical factor; labels (discomfort, pain, vasoconstriction pain) were varied as the psychological factor. Experiment I varied only water temperature; colder temperatures led to significantly lower BPT scores and significantly higher SR and AR scores. Experiment 2 varied only labeling and demonstrated that BPT decreased and AR increased as labels became more painful-sounding; in contrast, SR was unaffected by labeling. In Experiment 3 both the psychological and physical factors were varied simultaneously. Results indicated significantly higher BPT scores as the water temperature increased and the pain label became more benign. In addition, both SR and AR were sensitive to changes in temperature, whereas only AR was affected by changes in labeling.

Adult↗

Efficacy of Echinacea purpurea in patients with a common cold. A placebo-controlled, randomised, double-blind clinical trial.

Common colds are one of the most frequent acute illnesses with major economical impact. Echinaceae purpureae herba (Echinacin, EC31J0) has shown promising results in the relief of common cold symptoms and the time taken to improvement compared to placebo. This study was aimed to confirm these findings by performing a randomised, double-blind, placebo-controlled clinical trial. A total of 80 adult male or female patients with first signs of a cold were recruited. The number of days of illness with a complete picture of the common cold (defined by the modified Jackson score of at least 5 points and experience of rhinorrhea and/or a subjective sensation of having a cold) was the primary end-point. In the verum group the median time of illness was 6.0 days compared to 9.0 days in the placebo group, assigning zero time for patients without a complete picture (one-sided p = 0.0112). EC31J0 was well tolerated and clinically effective in alleviating symptoms more rapidly than placebo in patients with a common cold.

Adult↗

Major differences observed in transcript profiles of blueberry during cold acclimation under field and cold room conditions.

Our laboratory has been working toward increasing our understanding of the genetic control of cold hardiness in blueberry (Vaccinium section Cyanococcus) to ultimately use this information to develop more cold hardy cultivars for the industry. Here, we report using cDNA microarrays to monitor changes in gene expression at multiple times during cold acclimation under field and cold room conditions. Microarrays contained over 2,500 cDNA inserts, approximately half of which had been picked and single-pass sequenced from each of two cDNA libraries that were constructed from cold acclimated floral buds and non-acclimated floral buds of the fairly cold hardy cv. Bluecrop (Vaccinium corymbosum L.). Two biological samples were examined at each time point. Microarray data were analyzed statistically using t tests, ANOVA, clustering algorithms, and online analytical processing (OLAP). Interestingly, more transcripts were found to be upregulated under cold room conditions than under field conditions. Many of the genes induced only under cold room conditions could be divided into three major types: (1) genes associated with stress tolerance; (2) those that encode glycolytic and TCA cycle enzymes, and (3) those associated with protein synthesis machinery. A few of the genes induced only under field conditions appear to be related to light stress. Possible explanations for these differences are discussed in physiological context. Although many similarities exist in how plants respond during cold acclimation in the cold room and in the field environment, there are major differences suggesting caution should be taken in interpreting results based only on artificial, cold room conditions.

Acclimatization↗

History and geography of suicide: could genetic risk factors account for the variation in suicide rates?

The current state of knowledge of genetic predisposition towards the suicidal behavior allows for a question whether genetic risk factors account for the variation in suicide rates through time and space. Accordingly, the presented paper will attempt to tackle the genetics behind suicidal behavior from the perspective of the populational genetics. First, the variability of suicide rates across Europe is discussed. This is followed by a brief discussion of the J curve (on a map of Europe, the countries with a higher suicide rate form a so-called J curve, which starts in Finland and extends down to Slovenia), which maps on to the second principal component identified for European gene distribution, representing the ancestral adaptation to cold climates and the Uralic language dispersion. Furthermore, we will discuss whether the group of people living within the J-curve could share genes, which may not tolerate excessive amounts alcohol, the combination of which is more likely to end in suicidal behavior. Further along we list possible ways in which suicidal behaviour could have been selected for genetically in populations and identify those specific populations in which it may have appeared. Finally, we point at other locations in the world where a similar interplay of genes and environment has probably occurred, Greenland being the best example of the malignant interaction of alcohol consumption and the trait-like characteristics, which might constitute the vulnerability to suicidal behaviour.

Adaptation, Physiological↗

Postharvest heat and conditioning treatments activate different molecular responses and reduce chilling injuries in grapefruit.

A combination of hot water (a rinse at 62 degrees C for 20 s) and conditioning (pre-storage at 16 degrees C for 7 d) treatments synergistically reduced chilling injury development in grapefruit (Citrus paradisi, cv. "Star Ruby") during cold storage at 2 degrees C, suggesting that the treatments may activate different chilling tolerance responses. To study the molecular mechanisms involved, chilling- and conditioning-responsive genes were isolated by polymerase chain reaction (PCR) cDNA subtraction, cDNA libraries were constructed from hot water- and conditioning-treated fruit, and cDNA sequencing was used to identify putative stress-responsive and chilling tolerance genes. PCR cDNA subtraction revealed the identification of 17 chilling-responsive and heat- and conditioning-induced genes, and the expression patterns of 11 additional stress-related genes, antioxidant defensive genes, and genes encoding enzymes involved in membrane lipid modifications were characterized. It was found that hot water and conditioning treatments had little effect on gene expression by themselves, but rather had a priming effect, and enabled the fruit to activate their defence responses after subsequent exposure to chilling. RNA gel blot hybridizations revealed that the expression patterns of eight genes, including HSP19-I, HSP19-II, dehydrin, universal stress protein (USP), EIN2, 1,3;4-beta-D-glucanase, and superoxide dismutase (SOD), were specifically regulated by the heat treatment, and four genes, including fatty acid desaturase2 (FAD2) and lipid transfer protein (LTP), were specifically regulated by the conditioning treatment. Furthermore, four more genes were identified, including a translation initiation factor (SUI1), a chaperonin, and alcohol dehydrogenase (ADH), that were commonly regulated by both heat and conditioning treatments. According to these data, it is suggested that pre-storage heat and conditioning treatments may enhance fruit chilling tolerance by activating different molecular mechanisms. The hot water treatment activates mainly the expression of various stress-related genes, whereas the conditioning treatment activates mainly the expression of lipid membrane modification enzymes.

Acclimatization↗

Effect of temperature on cold-hardiness and tissue ice formation in the adult chrysomelid beetle Melasoma collaris L.

The freeze-tolerant chrysomelid beetle Melasoma collaris overwinters in plant litter on windswept ridges or covered with snow for 8-9 months in the Norwegian alpine region. Lower lethal temperature, supercooling and melting point depression were correlated to accumulation of glycerol. The lower limit of freeze tolerance was associated with the freezing of 73-75% body water. About 23-15.5% of the body water was osmotically inactive, and the highest percentage was revealed in individuals depleted of glycerol at 21 degrees C. A shift in cooling rate from 1 degrees Cmin(-1) to 1 degrees C every 13.5min lowered nucleating temperature markedly. The alteration in nucleating activity probably arises from the structure of the haemolymph nucleating agent that functions to slow embryo growth at the slow cooling rate. An enhanced supercooling is particularly beneficial in autumn before M. collaris has accumulated glycerol, since supercooled individuals accumulate glycerol in higher concentrations than frozen ones. Freezing at higher temperatures is probably a better survival strategy during brief intervals with pronounced decrease in air temperature.

Journal Article↗

Cold inhibition of cell volume regulation during the freezing of insect malpighian tubules.

Cells in freeze-tolerant tissues must survive substantial shrinkage during exposure to the hyperosmolarity that results as solutes are excluded from extracellular ice. We investigated the possibility that this hyperosmotic shock elicits an acute regulatory volume increase (RVI) by monitoring the response of epithelial cell volume in the Malpighian tubules of the New Zealand alpine weta (Hemideina maori) during exposure to low temperature/hyperosmolarity (mimicking freezing conditions) or during an actual freeze/thaw cycle. The cross-sectional area of cells in isolated Malpighian tubules was measured using differential interference contrast microscopy. At 20 degrees C, cells held in saline containing 400 mmol1-1 glucose exhibit an RVI in response to hyperosmotic shock. Cross-sectional area decreased by 30% immediately after a change from iso-osmotic (0.7 osmol1-1) to hyper-osmotic saline (2.1 osmol1-1, equal to the osmotic shock encountered during freezing to -4 degrees C) and then returned to 21% below the control value 30 min after the exposure. Although substantial cellular function of Malpighian tubules was retained at low temperature (the rate of fluid secretion by isolated tubules at 4 degrees C was 72% of that measured at 20 degrees C), no RVI was observed at 0% degrees C; cross-sectional area was 39% below the control value immediately after the hyperosmotic exposure and 36% below the control value 30 min after hyperosmotic exposure. Dibutyryl cyclic AMP potentiated the RVI observed at 20 degrees C, but failed to elicit an RVI at 0 degrees C. A substantial RVI was also absent when the saline contained trehalose rather than glucose, regardless of whether the tubules were held at 20 degrees C or 0 degrees C. The cross-sectional area of cells in saline containing glucose remained at approximately 30% below the control value during an entire 30 min period of actual freezing to -4 degrees C, suggesting that an acute volume regulatory response was in fact inhibited during mild freezing. The inhibition of an acute RVI during mild freezing may serve to avoid the energetic expenditure associated with volume regulation at a time when the normal defence of cell volume appears to be unnecessary.

Animals↗

Genotype-dependent transcriptional activation of novel repetitive elements during cold acclimation of alfalfa (Medicago sativa).

In a search for cold-regulated genes that are differentially expressed in alfalfa genotypes of contrasting freezing tolerance, we screened 1036 arrayed cDNA clones. The screening resulted in isolation of cDNA clones, which demonstrated dramatic differences in expression between hardy and un-hardy alfalfa varieties. Detailed analysis revealed that these cDNAs represent parts of novel non-coding repetitive elements carrying long-terminal repeats (LTR) and other retroelement-like features. Despite strong expression under low temperatures, DNA templates remained highly methylated, and a drug-induced decrease in methylation did not activate transcription under normal temperatures. We identified that these repetitive elements represent a large family and could insert into, or be adjacent to, the unrelated polyprotein sequences of putative retrotransposons. These retrotransposons also showed low temperature-induced transcriptional activation; however, this activation was not genotype-dependent. The retroelements described in this study are the first retroelement characterized in the Medicago genus. Furthermore, they represent the only known example of genotype-specific cold-induced transcriptional activation of multiple copies of a repetitive element whose expression is associated with a genotype difference in cold acclimation.

Acclimatization↗

Influenza vaccines in children.

Influenza is a common disease of childhood. Young children and children with high-risk medical conditions are at increased risk of being hospitalized when infected with influenza virus. Children of all ages have excess physician visits and receive excess antibiotic prescriptions during influenza season. The safety, immunogenicity, and efficacy of influenza vaccines in children are described in this review. Clinical trials and postlicensure experience have demonstrated that trivalent inactivated influenza vaccine is well-tolerated in children. Efficacy of the inactivated vaccine also has been demonstrated in numerous clinical trials. In comparison to trivalent inactivated influenza vaccine, investigational cold-adapted, live-attenuated influenza vaccine (LAIV) has the advantage of an intranasal route of administration. A large clinical trial demonstrated the tolerability and efficacy of the trivalent live, attenuated product in children 15 to 71 months of age. Pending information on safety and coadministration of this vaccine with other childhood vaccines will determine if it is licensed and recommended for use in children, including possible expanded indications for routine yearly administration to young children.

Administration, Intranasal↗

Topical anaesthesia for bladder biopsies and cautery: intravesical lidocaine versus caudal anaesthesia.

A total of 62 patients were randomized to receive bladder biopsy and cautery with either topical lidocaine anaesthesia or caudal anaesthesia. The patients were asked to describe the level of pain experienced during the procedure on a scale from 0 (no pain) to 5 (unbearable pain). In 29 patients receiving topical lidocaine anaesthesia, the mean value was 1.6 at cold-cup biopsies and 2.7 at cautery, which were considered to be tolerable for the patients. On the other hand, in 33 patients who had biopsies and cautery with caudal anaesthesia, the mean values were 0.8 and 1.0, respectively, which were significantly lower than those in patients receiving topical anaesthesia (p < 0.01). Serum lidocaine levels were measured in 5 patients at 15 minutes from the beginning of biopsies, and were negligible. These results revealed that caudal anaesthesia provided more effective pain relief, although most patients could tolerate biopsy and cautery with topical lidocaine anaesthesia. The technique of topical anaesthesia is very simple and no side effects were observed. We thus conclude that topical lidocaine anaesthesia is useful and safe for bladder biopsies and cautery in most cases.

Administration, Intravesical↗

Synergistic effect of microencapsulation and immunoalteration on islet allograft survival in bioartificial pancreas.

Recently, we reported successful transplantation (Tx) of microencapsulated (mc) islets. However, graft failure observed in several cases was associated with an increased foreign body reaction compared to long-term functioning grafts. This study was performed to investigate the impact of an immunoalterating islet pretreatment (12-14 days culture at 22 degrees C) on graft function. After microencapsulation in barium alginate beads the islets were cultured for another day. Diabetic LEWIS rats (blood glucose >19 mM) were transplanted with 3500 immunoaltered mc-Wistar islets intraperitoneally. Controls were transplanted with 3500 non-cultured syngeneic or allogeneic mc-islets. Additional syngeneic and allogeneic controls were transplanted with 6000 non-cultured, non-encapsulated islets intraperitoneally. Seventy percent of the recipients of microencapsulated, long-term low temperature cultured islets maintained normoglycemia at least for 15 weeks, while this was true in only 17% of those animals receiving microencapsulated non-pretreated allogeneic islets. Islets in non-encapsulated controls were rejected within several days. Graft function correlated with histologically proven viable islets within the capsules. Microencapsulation of islets markedly prolonged allograft survival compared to non-encapsulated islets; application of an immunoaltering low-temperature culture further improved graft function significantly. These data may support the hypothesis of induction of a reaction against microcapsules by the antigen release from the graft which may be avoided by immunoaltering islet pretreatment.

Alginates↗

Effects of cold exposure on submaximal exercise performance and adrenergic activation in patients with congestive heart failure and the effects of beta-adrenergic blockade (carvedilol or metoprolol).

Patients with congestive heart failure (CHF) exhibit a decrease in maximal exercise capacity in response to a cold environment. The aim of this study was to further investigate the impact of cold exposure on submaximal exercise capacity, systemic adrenergic drive, and the effects of long-term beta-adrenergic blockade on these parameters. Thirty-three patients with CHF, with exercise limited by dyspnea and left ventricular ejection fraction of 26 +/- 4%, were randomized to receive metoprolol or carvedilol for 6 months. The observations were compared with 12 age-matched healthy volunteers. Maximal exercise performance with gas exchange analyses were assessed using a ramp protocol, and endurance capacity was measured using 2 constant-load exercise tests performed randomly at 20 degrees C and -8 degrees C. Healthy volunteers increased their submaximal exercise time by 20% (1,353 +/- 455 [20 degrees C] vs 1,635 +/- 475 seconds [-8 degrees C]; p <0.05), whereas patients with CHF exhibited a 21% decrease in exercise time (1,182 +/- 549 [20 degrees C] vs 931 +/- 524 seconds [-8 degrees C]; p <0.05) at -8 degrees C. Beta blockers increased submaximal exercise duration at 20 degrees C (+261 +/- 617 seconds; p <0.05) and -8 degrees C (+374 +/- 729 seconds; p <0.05). Norepinephrine increased to a greater extent at 4 minutes and at the time of exhaustion (at -8 degrees C) only in patients with CHF. Beta-adrenergic blockade caused no significant decrease in plasma norepinephrine levels. Patients with symptomatic CHF exhibited a significant decrease in submaximal exercise time in response to moderate cold exposure. Beta-blocker therapy with either metoprolol or carvedilol significantly increases submaximal exercise time and attenuates the impact of cold exposure on functional capacity.

Adrenergic beta-Antagonists↗