Seroconversion and Abundance of IgG Antibodies against S1-RBD of SARS-CoV-2 and Neutralizing Activity in the Chilean Population.

COVID-19 is a pandemic caused by SARS-CoV-2. In Chile, half a million people have been infected and more than 16,000 have died from COVID-19. As part of the clinical trial NCT04384588, we quantified IgG against S1-RBD of SARS-CoV-2 (anti-RBD) in recovered people in Santiago and evaluated their suitability as COVID-19 convalescent plasma donors. ELISA and a luminescent SARS-CoV-2 pseudotype were used for IgG and neutralizing antibody quantification. 72.9% of the convalescent population (468 of 639) showed seroconversion (5-55 µg/mL anti-RBD IgG) and were suitable candidates for plasma donation. Analysis by gender, age, and days after symptom offset did not show significant differences. Neutralizing activity correlated with an increased concentration of anti-RBD IgG (p < 0.0001) and showed a high variability between donors. We confirmed that the majority of the Chilean patients have developed anti-SARS-CoV-2 antibodies. The quantification of anti-RBD IgG in convalescent plasma donors is necessary to increase the detection of neutralizing antibodies.

Outbreak characteristics associated with identification of contributing factors to foodborne illness outbreaks.

Information on the factors that cause or amplify foodborne illness outbreaks (contributing factors), such as ill workers or cross-contamination of food by workers, is critical to outbreak prevention. However, only about half of foodborne illness outbreaks reported to the United States' Centers for Disease Control and Prevention (CDC) have an identified contributing factor, and data on outbreak characteristics that promote contributing factor identification are limited. To address these gaps, we analyzed data from 297 single-setting outbreaks reported to CDC's new outbreak surveillance system, which collects data from the environmental health component of outbreak investigations (often called environmental assessments), to identify outbreak characteristics associated with contributing factor identification. These analyses showed that outbreak contributing factors were more often identified when an outbreak etiologic agent had been identified, when the outbreak establishment prepared all meals on location and served more than 150 meals a day, when investigators contacted the establishment to schedule the environmental assessment within a day of the establishment being linked with an outbreak, and when multiple establishment visits were made to complete the environmental assessment. These findings suggest that contributing factor identification is influenced by multiple outbreak characteristics, and that timely and comprehensive environmental assessments are important to contributing factor identification. They also highlight the need for strong environmental health and food safety programs that have the capacity to complete such environmental assessments during outbreak investigations.

Umbilical cord blood transplantation in hematologic diseases in patients over 15 years old: long-term experience at the Pontificia Universidad Católica de Chile.

Most patients who require a sibling stem cell transplantation do not have a matched donor. In our experience, only 1/3 patients have a matched unrelated donor (MUD); therefore, the majority of the patients will require umbilical cord blood (UCB). Patients treated for hematologic diseases with UCB transplants were included. UCB selection and conditioning regimens were performed according to the Minnesota group. Graft-versus-host disease (GVHD) prophylaxis, infection prevention, and patient care were performed according to institutional guidelines. We analyzed patients and graft demography, neutrophil and platelet recovery, chimerism kinetics, GVHD incidence, overall (OS), progression-free survival (PFS) and transplant-related mortality (TRM). We included 29 patients with a median age of 34.8 years (range 15-55). Eighteen were male and the median weight was 72.6 kg (range 54-100). Nineteen patients had acute leukemia. Myeloablative (MA) conditioning was used in 27 patients. Seventeen received double UCB (DUCB) grafts. Median total nucleated cell (10(7)/kg) was 4.2 (range 3.9-4.9) and 4.4 (range 2.8-6.3) for single UCB (SUCB) and DUCB transplants, respectively. Median time for neutrophil engraftment was 24.7 (range 14-43) and 25.8 days (range 14-52) after SUCB and DUCB transplants, respectively. Median time for platelet engraftment was 147 (range 30-516) and 81 days (range 37-200) after SUCB and DUCB transplants, respectively. All the patients receiving MA conditioning had >95% chimerism shortly after transplant. Cumulative incidence of grades II-IV and III-IV acute GVHD was 41% and 20%, respectively. Localized chronic GVHD was seen in 14% of the patients. Median follow-up was 16.7 months (range 1-63). Five-year OS and PFS were 38% and 39%, respectively. One-year TRM was 42%. UCB transplantation is associated with potential cure of hematologic malignancies and our results are similar to other series. Studies are needed to decrease mortality and improve immune reconstitution.

Estudio citogenético en 677 casos de aborto espontáneo / Cytogenetic study of 677 spontaneous abortions

INTRODUCCIÓN: La reproducción humana es un proceso relativamente ineficaz. Los abortos espontáneos ocurren entre el 15 a 20 por ciento de los embarazos clínicamente reconocidos. El impacto emocional se acentúa debido a la falta de diagnóstico. OBJETIVO: Describir la experiencia del Laboratorio de Citogenética de la Clínica Sanatorio Alemán de Concepción e identificarlas alteraciones más frecuentes y su relación estadística con la edad materna. MATERIAL Y MÉTODO: 677 muestras de tejido obtenidas de abortos espontáneos, ocurridos desde julio de1996 a abril de 2009. Es un trabajo de tipo transversal donde las muestras utilizadas son las vellosidades coriónicas, cultivadas en medios estandarizados. RESULTADOS: De las 677 muestras estudiadas, en 259 se obtuvo un cariotipo normal (38,3 por ciento). En 418 muestras se encontraron anomalías cromosómicas, correspondiendo estas a un 61,7 por ciento. Entre los cariogramas alterados se encontraron: 265 trisomías (63,4 por ciento), 83 poliploidías (19,9 por ciento), 48 monosomías (11,5 por ciento) y 22 alteraciones estructurales (5,3 por ciento). La trisomía más frecuente fue la 16 (34,4 por ciento), seguida de la trisomía 21 (13,6 por ciento). Se encontró una relación estadísticamente significativa entre la edad de la madre (> 37 años) y la presencia de alteraciones citogenéticas (p<0,0001). DISCUSIÓN: El 61,7 por ciento de los abortos presentó alguna alteración del cariotipo. La trisomía 16 fue la aberración más frecuente concordando con la literatura. La trisomía 21 se presentó en un 13,6 por ciento siendo más frecuente que lo encontrado en series extranjeras. En el grupo mayor de 37 años existe mayor prevalencia de anomalías cromosómicas siendo estadísticamente significativa (p<0,0001).

INTRODUCCION: The human reproduction is a relatively inefficient process. In the 15 to 20 percent of the pregnancy clinically diagnosticated finish in spontaneous abortions. The great emotional impact, that in many times is worst by the lack of diagnostic. OBJECTIVE: Describe experience of the Cytogenetic Laboratory of Clínica Sanatorio Alemán of Concepción Chile and determinate the frequency of alteration and his relationship with maternal age. MATERIAL AND METHOD: 677 samples of tissue of spontaneous abortions, taked from July, 1996 to April, 2009. It is a descriptive work; the samples are chorionic villous, cultivated in standard solutions. RESULTS: Of 677 samples in 259 was found a normal cariotype (38.3 percent). In 418 was found some type of chromosome aberrations (61.7 percent). The distribution of the abnormal result is the follow: 265 trisomies (63.4 percent), 83 polyploidy (19.8 percent), 48 monosomy (11.5 percent) and 22 abnormalities structures (5.3 percent). Of the trisomies the most recurrent is 16 trisomy with the 34.4 percent, follow by the 21 trisomy with 13.6 percent and the 22 trisomy with 12.8 percent. In the statistic analysis we found a statistically significant relation between the age of the mother (<38 years) and the development of chromosomal alterations (p<0.0001). DISCUSSION: The 61.7 percent of abortions show some cytogenetic alteration. The 16 trisomies were the most frequent, agreeing with the literature. The trisomy 21 was more common than published to date. In older women is most frequent found chromosome aberrations (p<0.0001).

Circadian desynchrony and metabolic dysfunction; did light pollution make us fat?

Circadian rhythms are daily oscillations in physiology and behaviour that recur with a period of 24h, and that are entrained by the daily photoperiod. The cycle of sunrise and sunset provided a reliable time cue for many thousands of years, until the advent of artificial lighting disrupted the entrainment of human circadian rhythms to the solar photoperiod. Circadian desynchrony (CD) occurs when endogenous rhythms become misaligned with daily photoperiodic cycles, and this condition is facilitated by artificial lighting. This review examines the hypothesis that chronic CD that has accompanied the availability of electric lighting in the developed world induces a metabolic and behavioural phenotype that is predisposed to the development of obesity. The evidence to support this hypothesis is based on epidemiological data showing coincidence between the appearance of obesity and the availability of artificial light, both geographically, and historically. This association links CD to obesity in humans, and is corroborated by experimental studies that demonstrate that CD can induce obesity and metabolic dysfunction in humans and in rodents. This association between CD and obesity has far reaching implications for human health, lifestyle and work practices. Attention to the rhythmicity of daily sleep, exercise, work and feeding schedules could be beneficial in targeting or reversing the modern human predisposition to obesity.

Association between mammalian lifespan and circadian free-running period: the circadian resonance hypothesis revisited.

Biological rhythms that oscillate with periods close to 24 h (circadian cycles) are pervasive features of mammalian physiology, facilitating entrainment to the 24 h cycle generated by the rotation of the Earth. In the absence of environmental time cues, circadian rhythms default to their endogenous period called tau, or the free-running period. This sustained circadian rhythmicity in constant conditions has been reported across the animal kingdom, a ubiquity that could imply that innate rhythmicity confers an adaptive advantage. In this study, we found that the deviation of tau from 24 h was inversely related to the lifespan in laboratory mouse strains, and in other rodent and primate species. These findings support the hypothesis that misalignment of endogenous rhythms and 24 h environmental cycles may be associated with a physiological cost that has an effect on longevity.

Separating cause from effect: how does insulin/IGF signalling control lifespan in worms, flies and mice?

Ageing research has been revolutionized by the use of model organisms to discover genetic alterations that can extend lifespan. In the last 5 years alone, it has become apparent that single gene mutations in the insulin and insulin-like growth-factor signalling pathways can lengthen lifespan in worms, flies and mice, implying evolutionary conservation of mechanisms. Importantly, this research has also shown that these mutations can keep the animals healthy and disease-free for longer and can alleviate specific ageing-related pathologies. These findings are striking in view of the negative effects that disruption of these signalling pathways can also produce. Here, we summarize the body of work that has lead to these discoveries and point out areas of interest for future work in characterizing the genetic, molecular and biochemical details of the mechanisms to achieving a longer and healthier life.

The use of clinical profiles in the investigation of foodborne outbreaks in restaurants: United States, 1982-1997.

Improving the efficiency of outbreak investigation in restaurants is critical to reducing outbreak-associated illness and improving prevention strategies. Because clinical characteristics of outbreaks are usually available before results of laboratory testing, we examined their use for determining contributing factors in outbreaks caused by restaurants. All confirmed foodborne outbreaks reported to the Centers for Disease Control and Prevention (CDC) from 1982 to 1997 were reviewed. Clinical profiles were developed based on outbreak characteristics. We compared the percentage of contributing factors by known agent and clinical profile to their occurrence in outbreaks of unclassified aetiology. In total, 2246 foodborne outbreaks were included: 697 (31%) with known aetiology and 1549 (69%) with aetiology undetermined. Salmonella accounted for 65% of outbreaks with a known aetiology. Norovirus-like clinical profiles were noted in 54% of outbreaks with undetermined aetiology. Improper holding times and temperatures were associated with outbreaks caused by Clostridium perfringens, Bacillus cereus, Staphylococcus aureus, and Salmonella, and also with outbreaks of undetermined aetiology that fitted diarrhoea-toxin and vomiting-toxin clinical profiles. Poor personal hygiene was associated with norovirus, Shigella, and Salmonella, and also with outbreaks that fitted norovirus-like and vomiting-toxin clinical profiles. Contributing factors were similar for outbreaks with known aetiology and for those where aetiology was assigned by corresponding clinical profile. Rapidly categorizing outbreaks by clinical profile, before results of laboratory testing are available, can help identification of factors which contributed to the occurrence of the outbreak and will promote timely and efficient outbreak investigations.

Pancreatic deletion of insulin receptor substrate 2 reduces beta and alpha cell mass and impairs glucose homeostasis in mice.

AIMS/HYPOTHESIS: Insulin signalling pathways regulate pancreatic beta cell function. Conditional gene targeting using the Cre/loxP system has demonstrated that mice lacking insulin receptor substrate 2 (IRS2) in the beta cell have reduced beta cell mass. However, these studies have been complicated by hypothalamic deletion when the RIPCre (B6.Cg-tg(Ins2-cre)25Mgn/J) transgenic mouse (expressing Cre recombinase under the control of the rat insulin II promoter) is used to delete floxed alleles in insulin-expressing cells. These features have led to marked insulin resistance making the beta cell-autonomous role of IRS2 difficult to determine. To establish the effect of deleting Irs2 only in the pancreas, we generated PIrs2KO mice in which Cre recombinase expression was driven by the promoter of the pancreatic and duodenal homeobox factor 1 (Pdx1, also known as Ipf1) gene. MATERIALS AND METHODS: In vivo glucose homeostasis was examined in PIrs2KO mice using glucose tolerance and glucose-stimulated insulin secretion tests. Endocrine cell mass was determined by morphometric analysis. Islet function was examined in static cultures and by performing calcium imaging in Fluo3am-loaded beta cells. Islet gene expression was determined by RT-PCR. RESULTS: The PIrs2KO mice displayed glucose intolerance and impaired glucose-stimulated insulin secretion in vivo. Pancreatic insulin and glucagon content and beta and alpha cell mass were reduced. Glucose-stimulated insulin secretion and calcium mobilisation were attenuated in PIrs2KO islets. Expression of the Glut2 gene (also known as Slc2a2) was also reduced in PIrs2KO mice. CONCLUSIONS/INTERPRETATION: These studies suggest that IRS2-dependent signalling in pancreatic islets is required not only for the maintenance of normal beta and alpha cell mass but is also involved in the regulation of insulin secretion.

Effects of aging and caloric restriction on mitochondrial energy production in gastrocnemius muscle and heart.

Mitochondria are chronically exposed to reactive oxygen intermediates. As a result, various tissues, including skeletal muscle and heart, are characterized by an age-associated increase in reactive oxidant-induced mitochondrial DNA (mtDNA) damage. It has been postulated that these alterations may result in a decline in the content and rate of production of ATP, which may affect tissue function, contribute to the aging process, and lead to several disease states. We show that with age, ATP content and production decreased by approximately 50% in isolated rat mitochondria from the gastrocnemius muscle; however, no decline was observed in heart mitochondria. The decline observed in skeletal muscle may be a factor in the process of sarcopenia, which increases in incidence with advancing age. Lifelong caloric restriction, which prolongs maximum life span in animals, did not attenuate the age-related decline in ATP content or rate of production in skeletal muscle and had no effect on the heart. 8-Oxo-7,8-dihydro-2'-deoxyguanosine in skeletal muscle mtDNA was unaffected by aging but decreased 30% with caloric restriction, suggesting that the mechanisms that decrease oxidative stress in these tissues with caloric restriction are independent from ATP availability. The generation of reactive oxygen species, as indicated by H2O2 production in isolated mitochondria, did not change significantly with age in skeletal muscle or in the heart. Caloric restriction tended to reduce the levels of H2O2 production in the muscle but not in the heart. These data are the first to show that an age-associated decline in ATP content and rate of ATP production is tissue specific, in that it occurs in skeletal muscle but not heart, and that mitochondrial ATP production was unaltered by caloric restriction in both tissues.

Resting metabolic rate and morphology in mice (Mus musculus) selected for high and low food intake.

We investigated the relationship between resting metabolic rate (RMR) and various morphological parameters in non-breeding mice, selected for high and low food intake corrected for body mass. RMR was measured at 30 degrees C, and mice were subsequently killed and dissected into 19 body components. High-food-intake mice had significantly greater body masses and a significantly elevated RMR compared with the low-intake mice. Data pooled across strains indicated that body mass, sex and strain together explained over 56 % of the observed variation in RMR. The effects of strain and sex on RMR and tissue morphology were removed, and three separate statistical analyses to investigate the relationship between RMR and organ morphology were performed: (i) employing individual regression analysis with each tissue component as a separate predictor against RMR; (ii) individual regression analysis with residual organ mass against residual RMR (i.e. with strain, sex and body mass effects removed); and (iii) pooling of some organ masses into functional groupings to reduce the number of predictors. Liver mass was the most significant morphological trait linked to differences in RMR. Small intestine length was significantly greater in the high-intake line; however, no difference was observed between strains in the dry mass of this organ, and there was no evidence to associate variability in the mass of the alimentary tract with variability in RMR. The effects of strain on RMR independent of the effect on body mass were consistent with the anticipated effect from the strain differences in the size of the liver.

Thermoregulatory responses of two mouse Mus musculus strains selectively bred for high and low food intake.

We examined the thermoregulatory responses of male and female mice Mus musculus that had been divergently selected on voluntary food intake, corrected for body mass, to produce a high-intake and a low-intake strain. Resting metabolic rate was determined by indirect calorimetry (at 30 degrees C, 25 degrees C, 15 degrees C and 5 degrees C). Body temperature responses were measured in a separate group of mice in a parallel protocol. High-intake mice had significantly elevated body masses compared to low-intake mice in both sexes. Lower critical temperature in both strains appeared to be around 28 degrees C. At 30 degrees C there was a significant strain effect on resting metabolic rate, with high strain mice having greater metabolism than low strain mice. Sex and body mass were not significant main effects on resting metabolic rate and there were no significant interactions. Body temperature measured at 30 degrees C, 25 degrees C, 15 degrees C and 5 degrees C differed significantly between sexes (females higher) and there was a significant sexxbody mass interaction effect, but there was no difference between strains. Thermal conductance was significantly related to strain and sex, mice from the high strain and males having greater thermal conductances than mice from the low strain and females. Artificial selection has resulted in high-intake mice having greater body masses and greater thermal conductances, which together account for up to 45% of the elevated daily energy demands that underpin the increase in food intake. The greater levels of food intake were also associated with higher resting metabolic rates at 30 degrees C.

Effect of long-term cold exposure on antioxidant enzyme activities in a small mammal.

Aerobic organisms continually face exposure to reactive oxygen species (ROS) and many have evolved sophisticated antioxidant systems to effectively remove them. Any increase in ROS production or weakening in this defense system may ultimately lead to oxidative stress and cellular damage. We investigated whether long-term cold exposure, which is known to lead to an elevation in metabolic rate, increased the activities of the ROS-scavenging enzymes, catalase (CAT), selenium-dependent glutathione peroxidase (GPx), and total superoxide dismutase (Total-SOD) in liver, cardiac muscle, kidney, skeletal muscle (vastus lateralis), and duodenum of short-tailed field voles (Microtus agrestis), born and maintained at either 8 +/- 3 degrees C or 22 +/- 3 degrees C. CAT, GPx, and Total-SOD activities were determined at age 61 +/- 1.9 days. An increase in CAT activity in voles maintained at 8 +/- 3 degrees C was observed in skeletal muscle (71%) and kidney (20%), with both CAT and GPx activities significantly elevated (by 40 and 43%, respectively) in cardiac muscle, when compared to voles at 22 +/- 3 degrees C. Total-SOD activity and protein content did not differ significantly between groups in any tissue. We suggest that the compensatory increases in CAT (skeletal muscle, cardiac muscle, kidney) and GPx (cardiac muscle), but not Total-SOD activities, resulting from long-term cold exposure may reflect the elevated metabolic rate, and possibly also increased ROS production, at this time.

Effect of pregnancy on exposure to malaria mosquitoes.

Pregnant women attracted twice the number of Anopheles gambiae complex--the predominant African malaria-carrying mosquito--than did their non-pregnant counterparts. We postulate that physiological and behavioural changes that occur during pregnancy are responsible for increased attractiveness, which could be important in intervention strategies aimed at protecting this high-risk group against malaria.

PIP: In Africa, malaria has been the major cause of illness and an indirect cause of death among pregnant women. It is also an important cause of stillbirths, low birth weight and early infant mortality. A comparative study was conducted in Gambia to examine the relative attractiveness of pregnant and nonpregnant women to mosquitoes. For 3 consecutive nights, 12 groups of women consisting of 3 pregnant and nonpregnant women in each group were studied. After adjusting for variation between huts and trials, Anopheles gambiae (main malaria vectors in Africa) were found to be more attracted to pregnant women (mean, 6.33 per night [95% confidence interval, 4.5-8.7]) than to nonpregnant women (3.1 [2.1-4.5]; p = 0.0002). Similar findings were also found with Mansonia spp. (7.6 [5.8-10.0] vs. 5.7 [4.1-7.8]; p = 0.0008), but differences were of borderline significance with other culicines. Two physiological factors underlying increased attractiveness during pregnancy were increased heat and increased release of volatile substances from the skin surface. Overall, this study confirms the increased risk of malaria and other mosquito-born diseases among pregnant women, and underlines the importance of protecting these women through immunity and nutrition.

Male short-tailed field voles (Microtus agrestis) build better insulated nests than females.

Nest construction is an extremely widespread behaviour. In small endotherms the nest serves primarily to provide insulation, and thereby retard heat loss of the constructor, or its offspring. In arctic and temperate regions many small mammals build nests to protect themselves from low ambient temperatures. We measured the physical properties of nests built by short-tailed field voles Microtus agrestis that were kept in captivity under cold conditions. The most important factor influencing nest insulation was nest wall thickness; however, nests with thick walls also contained more nesting material. Insulative capacity of the nest did not reach an asymptote up to nests containing 20 g of material. Nest insulation was not correlated with resting metabolic rate, body mass or body composition of the vole that constructed the nest. However, nests built by males had greater insulation than those made by females; males also had significantly lower food intake rates when compared to females with nests. No significant difference was observed in either fat mass or whole animal thermal conductance between males and females. Thermal conductance did increase significantly with increasing body mass, although not with resting metabolic rate. Voles with nests for prolonged periods had lower food intakes than voles without nests. The absolute saving averaged 1.9 g and was independent of body mass. This was a 28% saving on intake for a 22-g vole but only an 18% saving for a 40-g individual. When voles had nests for short periods they used the energy they saved to reduce food intake and increase body mass.