Determining the acceptability of testing contacts of confirmed COVID-19 cases to improve secondary case ascertainment.

BACKGROUND: UK asymptomatic contacts of confirmed COVID-19 cases are not routinely tested for SARS-CoV-2. Testing contacts may improve case ascertainment and reduce onward transmission. This study investigated the acceptability of SARS-CoV-2 testing among contacts of confirmed cases as an integral part of the contact-tracing process. METHODS: A cross-sectional descriptive survey of case contacts was conducted in the UK. All contacts who completed a telephone call with the NHS Test and Trace Agile Lighthouse team were eligible for inclusion and were offered a molecular test. Consenting participants were sent a self-swab kit. RESULTS: Of the 1523 individuals contacted, 602 (39.5%) accepted the test offer. Of the 240 (39.9%) samples returned for testing, 16.3% tested polymerase chain reaction-positive for SARS-CoV-2.Most individuals who declined with a reason (638/905; 70.5%) reported they had already taken or booked a SARS-CoV-2 test, or were part of a testing programme. Matched laboratory records confirmed 73.1% of those who declined were tested by another route. CONCLUSIONS: Most case contacts were tested, either through arranging a test by themselves or by accepting the study offer. Results demonstrate high acceptability, with substantial test positivity, indicating that there is public health benefit in offering tests to contacts as a routine part of the contact-tracing process.

The invasion of Patagonia by Chinook salmon (Oncorhynchus tshawytscha): inferences from mitochondrial DNA patterns.

The Chinook salmon Oncorhynchus tshawytscha, which was introduced deliberately in Chile four decades ago for sport fishing and aquaculture, represents a rare example of a successful translocation of an anadromous Pacific salmon into the southern Hemisphere, offering a unique opportunity to examine the role of introduction history and genetic variability in invasion success. We used historical information and mitochondrial displacement loop sequences (D-loop) from seven colonized sites in Chile and Argentina and from native and naturalized Chinook salmon populations to determine population sources and to examine levels of genetic diversity associated with the invasion. The analysis revealed that the Chinook salmon invasion in Patagonia originated from multiple population sources from northwestern North America and New Zealand, and admixed in the invaded range generating genetically diverse populations. Genetic analyses further indicated that the colonization of new populations ahead of the invasion front appear to have occurred by noncontiguous dispersal. Dispersal patterns coincided with ocean circulation patterns dominated by the West Wind Drift and the Cape Horn Currents. We conclude that admixture following multiple introductions, as well as long-distance dispersal events may have facilitated the successful invasion and rapid dispersal of Chinook salmon into Patagonia.

Circadian and light regulation of oxytocin and parvalbumin protein levels in the ciliated ependymal layer of the third ventricle in the C57 mouse.

The walls of the third ventricle have been proposed to serve as a bidirectional conduit for exchanges between the neural parenchyma and the cerebrospinal fluid. In immunohistochemical studies of mice, we observed that light exposure and circadian phase affected peptide staining surrounding the third ventricle at the level of the suprachiasmatic nuclei. Under high magnification, we observed robust staining for the neurohormone oxytocin and the calcium-binding protein parvalbumin associated with cilia extending into the third ventricle from the surrounding ventricular wall; no similar staining was observed for vasopressin or calbindin. Retinal illumination had opposite effects on levels of parvalbumin and oxytocin in the cilia: light exposure during late subjective night increased oxytocin staining, but decreased parvalbumin staining in the cilia. Preventing cellular transport with colchicine eliminated immunohistochemical staining for oxytocin in the cilia. There was also a significant daily rhythm of oxytocin immunostaining in the third ventricle wall, and in magnocellular neurons in the anterior hypothalamus. The results suggest that environmental lighting and circadian rhythms regulate levels of oxytocin in the cerebrospinal fluid, possibly by regulating movement of oxytocin through the third ventricle wall.

Food-entrained circadian rhythms in rats are insensitive to deuterium oxide.

Rats anticipate a scheduled daily meal by entrainment of a circadian pacemaker separate from the light-entrainable circadian pacemaker located in the suprachiasmatic nuclei (SCN). The site and molecular mechanisms of the food-entrainable pacemaker are unknown. The intrinsic period (tau) of the SCN pacemaker is significantly lengthened by deuteriation. Sensitivity of food-entrained circadian rhythms to D(2)O (25% in drinking water) was evaluated in intact and SCN-ablated rats entrained to daily feeding schedules. In intact rats fed ad-libitum, D(2)O lengthened tau sufficiently to drive activity rhythms out of entrainment to the light-dark cycle. By contrast, food-entrained rhythms were surprisingly resistant to modulation by D(2)O. The mean daily onset time of food anticipatory activity in rats with complete SCN-ablations was not affected by up to 28 days of D(2)O intake. Transient delays and disruption of anticipatory activity were evident in intact and one partial SCN-ablated rat during D(2)O treatment, but these are interpretable as effects of coupling and/or masking interactions between a D(2)O-sensitive light-entrainable pacemaker, and a D(2)O-resistant food-entrained pacemaker. Differential sensitivity to D(2)O suggests diversity in the molecular mechanisms of food- and light-entrainable circadian pacemakers in mammals. D(2)O may have utility as a screening test to identify putative food-entrainable pacemakers from among those central and peripheral tissues that can express circadian oscillations of clock genes independent of the SCN.

Predictors of radial artery patency for coronary bypass operations.

BACKGROUND: Few data exist regarding angiographic predictors of radial artery patency for coronary bypass grafting, and the benefit of calcium antagonists is not clear. METHODS: One hundred fifteen patients were studied who had myocardial revascularization with the radial artery plus internal mammary and vein grafts with 3.5 +/- 1.1 grafts per patient. Sixty-three patients received diltiazem and 52 patients did not. Base line and follow-up angiographies were analyzed 1 year postoperatively in 50 of these patients with a quantitative computerized method. RESULTS: One hundred fourteen patients survived and were followed for 30.1 +/- 12.6 months. Patency for mammary grafts was 100%, for radial grafts it was 80%, and for saphenous vein grafts it was 68%. Patent radial artery grafts had significantly greater degree of stenosis in the native vessels than occluded grafts (73% +/- 14% vs 40% +/- 24%), (p = 0.0007; confidence interval = 95%). Radial artery patency increased to 92% when arteries with 70% or more stenosis were considered. No differences were observed for clinical and angiographic end points in the patients that received diltiazem compared with the rest who had not. CONCLUSIONS: The degree of stenosis in the native coronary artery significantly influences the patency rate of radial artery grafts, independent of diltiazem.

Light augments FOS protein induction in brain of short-term enucleated hamsters.

FOS protein is synthesized in neuronal nuclei in response to a variety of environmental stimuli and has been used as a marker of stimulus-specific brain function. The present studies were initiated to examine the effects of ultraviolet light on the induction of FOS protein immunoreactivity (FOS-IR) in several brain regions of adult male hamsters. Experiment 1 confirmed previous observations of FOS-IR induced in visual cortex in response to ultraviolet light. However, protein was also induced by ultraviolet or white light in a variety of other areas and induction occurred in both sighted and enucleated animals. Therefore, experiments were conducted to evaluate the effects of a 514 nm light on FOS-IR induction in blind or sighted animals. Experiments 2 and 3 were performed during the early subjective night and mid-subjective day, respectively, using animals about 4 days after bilateral enucleation or sham surgery. In Experiment 2, light and enucleation independently and interactively resulted in increased FOS-IR neuronal nuclei counts. In Experiment 3, there was a main effect of enucleation and an interaction between enucleation and light condition, but no main effect of light. In Experiment 4, conducted during the early subjective night using animals enucleated 60 days earlier, there were neither effects of light or enucleation. The results support the view that, under certain conditions related to subjective time of day and time since enucleation, light can act through unknown extraocular mechanisms to modify brain activity. Further, short term enucleation itself induces widespread alteration in brain function as indicated by increased FOS-IR expression. The results specifically do not support a role for extraretinal photoreception with respect to direct circadian rhythm regulation.

Phase-shifting effects of pituitary adenylate cyclase activating polypeptide on hamster wheel-running rhythms.

Pituitary adenylate cyclase activating polypeptide (PACAP38) is a putative neurochemical of the main retinal input to the mammalian circadian pacemaker housed in the suprachiasmatic nucleus (SCN). We assessed the phase-resetting effects of microinjection of PACAP38 into the SCN region on hamster wheel-running rhythms. When administered during the middle of the subjective day, PACAP38 evoked large but transient phase advances ( approximately 60 min), that were followed by small, steady-state phase delays. During the early subjective night, PACAP38 elicited small to moderate phase delays without any detectable concentration-dependence. Late in the subjective night, PACAP38 had no significant effects. Saline microinjection had no effect at any phase tested. These findings show that PACAP38 has small to moderate effects on the phase of the hamster SCN circadian pacemaker, including significant phase delays early in the subjective night.

[Treatment of advanced heart failure by heart transplantation]. / Tratamiento de la insuficiencia cardíaca avanzada mediante transplante de corazón.

BACKGROUND: Heart transplantation currently provides the most effective treatment for advanced heart failure. However, medical therapy for this condition has also improved, heart donors are scarce and the cost of the procedure is high. Therefore the indications and management of these patients need reevaluation. AIM: To analyze the results of 24 patients submitted to heart transplantation for end-stage heart failure needing repeated hospitalizations and i.v. inotropes for compensation. PATIENTS AND METHODS: The group was comprised by 21 men and 3 women with a mean age of 36.8 years, mean left ventricular ejection fraction 19 +/- 4.5%, mean systolic pulmonary artery pressure 48 +/- 13 mmHg (24-70) and mean pulmonary vascular resistance 2.6 Wood Units (1-5). Fourteen patients (58%) had a previous median sternotomy. Immunosuppression did not include induction therapy and steroids were discontinued early. RESULTS: Operative mortality was 4% at 30 days. Actuarial survival at one year was 90% and at 5 years 72%. Freedom from rejection at one year was 76% and at 5 years 50%. Freedom from infection was 70% at one year and 56.5% at five years. All patients with more than 3 months of follow-up were in functional class I. CONCLUSIONS: These results justify the proposed modifications for transplantation protocols.

[The collagen of the restenosis post angioplasty with stent: Is its origin in intima or adventitia?]. / El colágeno de la reestenosis post angioplastia con stent: se origina en la íntima o en la adventicia?

BACKGROUND: Restenosis post stenting is due to the deposit of extracellular matrix, mainly collagen in the neointima. Controversy exists regarding if collagen is generated locally or by immigration from the adventitia. AIM: To study the fibrocellular response after stent implantation in rabbit iliac arteries. To observe, by immunohistochemistry and in situ hybridization, if collagen type I mRNA is expressed in the neointima, in the media or in the adventitia. MATERIAL AND METHODS: Thirty eight white rabbits (New Zealand) of 4 kg received an hypercholesterolemic diet during 1 month. After this period, in all but 6 of them, an angioplasty with stent implantation was performed via right carotid artery in both iliac arteries, using a 1:1.3 relationship regarding the reference vessel. Angiograms were performed at day 0, 4, 21, and 40, followed by paraffin fixation of the injured segments, immunohistochemistry for alpha-actin and in situ hybridization to detect procollagen type I (alpha 1R1) mRNA. RESULTS: No hybridization was observed in non injured arteries or at day 0 (n = 6). Expression of alpha 1R1 mRNA was observed in the neointima starting at day 4 after stenting (n = 8). At day 21 (n = 8) hybridization of procollagen type I was not only observed in the neointima, but also in the media, which became equally intense in both areas. At day 40 (n = 6) hybridization was observed similarly in the media and adventitia. CONCLUSIONS: In this model, hybridization of procollagen type I started in the neointima, then involved the media and finally the adventitia. This finding might be useful for designing therapies to be delivered locally at the end of an angioplasty to prevent collagen deposition in the neointima.

Hippocampal involvement in the expression of kindling-induced fear in rats.

Kindling dramatically increases fearful behavior in rats. Because kindling-induced fear increases in magnitude as rats receive more stimulations, kindling provides a superb opportunity to study the nature and neural mechanisms of fear sensitization. Interestingly, these changes in behavior are accompanied by increased binding to inhibitory receptors and decreased binding to excitatory receptors in the CA1 and dentate gyrus regions of the hippocampus. This led us to hypothesize that kindling-induced fear may result from an increased inhibitory tone within hippocampal circuits. To test this hypothesis, we investigated FOS protein immunoreactivity in hippocampal and amygdalar regions of kindled rats that were exposed to an unfamiliar open field. We found that FOS immunoreactivity was significantly decreased in the CA1 region, dentate gyrus, and perirhinal cortex of kindled rats compared to sham-stimulated rats. These results support our hypothesis that kindling-induced fear may be produced by inhibition within hippocampal circuits. They also suggest that neural changes within the hippocampus may be important for the sensitization of fear.

The hamster circadian rhythm system includes nuclei of the subcortical visual shell.

The clock regulating mammalian circadian rhythmicity resides in the suprachiasmatic nucleus. The intergeniculate leaflet, a major component of the subcortical visual system, has been shown to be essential for certain aspects of circadian rhythm regulation. We now report that midbrain visual nuclei afferent to the intergeniculate leaflet are also components of the hamster circadian rhythm system. Loss of connections between the intergeniculate leaflet and visual midbrain or neurotoxic lesions of pretectum or deep superior colliculus (but not of the superficial superior colliculus) blocked phase shifts of the circadian activity rhythm in response to a benzodiazepine injection during the subjective day. Such damage did not disturb phase response to a novel wheel stimulus. The amount of wheel running or open field locomotion were equivalent in lesioned and control groups after benzodiazepine treatment. Electrical stimulation of the deep superior colliculus, without its own effect on circadian rhythm phase, greatly attenuated light-induced phase shifts. Such stimulation was associated with increased FOS protein immunoreactivity in the suprachiasmatic nucleus. The results show that the circadian rhythm system includes the visual midbrain and distinguishes between mechanisms necessary for phase response to benzodiazepine and those for phase response to locomotion in a novel wheel. The results also refute the idea that benzodiazepine-induced phase shifts are the consequence of induced locomotion. Finally, the data provide the first indication that the visual midbrain can modulate circadian rhythm response to light. A variety of environmental stimuli may gain access to the circadian clock mechanism through subcortical nuclei projecting to the intergeniculate leaflet and, via the final common path of the geniculohypothalamic tract, from the leaflet to the suprachiasmatic nucleus.

[D/D genotype of the gene for angiotensin converting enzyme as a risk factor for post-stent coronary restenosis]. / El genotipo D/D del gen de la enzima conversiva de la angiotensina como factor de riesgo de reestenosis post-stent coronario.

INTRODUCTION: Although intracoronary stenting has decreased restenosis rate compared to percutaneous balloon angioplasty, still a high number of patients develop in-stent restenosis, which is an entity primarily due to tissue proliferation. Experimental studies have indicated that the renin-angiotensin system is involved in neointimal hyperplasia. Plasma and cellular levels of ACE are associated with an I/D polymorphism in the ACE gene. Indeed, DD subjects have the higher ACE levels. The purpose of this study was to explore the possibility that the I/D polymorphism might be related with in-stent restenosis. METHODS: We studied the ACE polymorphism in 48 consecutive patients who underwent successful implantation of an elective coronary stent in native coronary vessels and had a 6 month angiographic follow up. Restenosis (50% of the reference vessel) was observed in 23/48 patients. Patients with or without restenosis did not differ in demographic or clinical variables like diabetes, plasma cholesterol levels or in quantitative angiographic parameters such as vessel reference size or minimal lumen diameter after stent implantation. RESULTS: I/D polymorphism was distributed as follows: 22.9% of the patients were D/D; 14.5% were I/I and 62.5% of the patients were heterozygous I/D. The presence of restenosis was strongly related with the I/D polymorphism: 81.8% of the patients with D/D genotype had restenosis, compared with 40.0% of I/D patients and only 14.2% of the I/I patients (chi 2 p < 0.01). CONCLUSIONS: In this limited cohort, homocygous D/D of the ACE gene was significantly associated with in-stent restenosis, whereas restenosis was infrequent in patients with the I/I genotype.

Enhanced food-anticipatory circadian rhythms in the genetically obese Zucker rat.

This study examines the effects of the leptin receptor mutation in obese Zucker rats on entrainment of food-anticipatory rhythms to daily feeding schedules. Leptin is secreted by adipocytes in proportion to fat content, exhibits a daily rhythm in plasma that is synchronized to feeding time, and inhibits activity of arcuate neuropeptide Y neurons that stimulate feeding behavior and regulate metabolism. Activity within this neuropeptide Y system is enhanced by food deprivation and attenuated by overfeeding and diet-induced obesity. Diet-induced obesity, in turn, attenuates food-anticipatory rhythms. If the effects of obesity on food-entrained rhythms are mediated by leptin inhibition of neuropeptide Y neurons, then these rhythms may be enhanced in leptin-insensitive Zucker obese rats. Alternatively, if daily rhythms of leptin mediate the generation or entrainment of these rhythms, Zucker rats may fail to anticipate daily feedings. Zucker obese and lean rats received food for 3 h/day during the midlight period. Both groups exhibited significant food-anticipatory activity that persisted during three cycles of food deprivation, but this rhythm was significantly more robust in obese rats, when expressed as anticipation and persistence ratios, and as peak values. Anticipatory rhythms did not persist in either group when food was provided ad lib. These results indicate that central actions of leptin may mediate the inhibitory effects of obesity on the expression of food-anticipatory rhythms in rats, but do not mediate the inhibitory effects of ad lib food access, and do not serve as necessary internal entrainment cues or clock components for the food-entrainable circadian system.

Serotonin antagonists do not attenuate activity-induced phase shifts of circadian rhythms in the Syrian hamster.

A variety of observations from several rodent species suggest that a serotonin (5-HT) input to the suprachiasmatic nucleus (SCN) circadian pacemaker may play a role in resetting or entrainment of circadian rhythms by non-photic stimuli such as scheduled wheel running. If 5-HT activity within the SCN is necessary for activity-induced phase shifting, then it should be possible to block or attenuate these phase shifts by reducing 5-HT release or by blocking post-synaptic 5-HT receptors. Animals received one of four serotonergic drugs and were then locked in a novel wheel for 3 h during the mid-rest phase, when novelty-induced activity produces maximal phase advance shifts. Drugs tested at several doses were metergoline (5-HT1/2 antagonist; i.p.), (+)-WAY100135 (5-HT1A postsynaptic antagonist, which may also reduce 5-HT release by an agonist effect at 5-HT1A raphe autoreceptors; i.p.), NAN-190 (5-HT1A postsynaptic antagonist, which also reduces 5-HT release via an agonist effect at 5-HT1A raphe autoreceptors; i.p.) and ritanserin (5-HT2/7 antagonist; i.p. and i.c.v.). Mean and maximal phase shifts to running in novel wheels were not significantly affected by any drug at any dose. These results do not support a hypothesis that 5-HT release or activity at 5HT1, 2 and 7 receptors in the SCN is necessary for the production of activity-induced phase shifts in hamsters.

Serotonin and feedback effects of behavioral activity on circadian rhythms in mice.

Wheel running activity can shorten the period (tau) of circadian rhythms in rats and mice. The role of serotonin (5HT), in this effect of behavior on circadian pacemaker function, was assessed by measuring tau during wheel-open and wheel-locked conditions in mice sustaining neurotoxic 5HT lesions directed at the suprachiasmatic nucleus (SCN). Intact mice exhibited a significant lengthening of tau (approximately 10 min) within 3 weeks when running wheels were locked. Mice with immunocytochemically confirmed 5HT depletion showed significantly longer tau than intact mice during wheel access, and did not show a significant change in tau up to 6 weeks after wheels were locked. In these mice, variability of tau across wheel access conditions was similar in magnitude to tau variability in intact mice at two time points without wheel access (+/- 3 min). 5HT-depleted mice also exhibited significantly longer activity periods (alpha), and a significantly delayed peak of activity within alpha. Previous studies show that a delayed peak of activity within alpha is associated with longer tau. Group differences in tau, and apparent failure of wheel-locking to lengthen tau in mice with 5HT lesions, may thus be due to loss of a serotonergic behavioral input pathway to the SCN, or to a lesion-induced change in the waveform of the activity rhythm.

[Unstable angina: immediate and one-year results of transluminal coronary angioplasty treatment]. / Angina inestable: resultados inmediatos y a un año del tratamiento con angioplastía coronaria transluminal percutánea.

BACKGROUND: Unstable angina is characterized by angina at rest, angina of recent onset or accelerating angina. It is caused by a fissure or ulceration of an atheromatous plaque leading to thrombi formation and coronary spasm. AIM: To report the immediate and late results of coronary angioplasty in patients with unstable angina. PATIENTS AND METHODS: Eight hundred twenty eight patients were subjected to coronary arteriography between January 1994 and June 1996. Of these, 242 were subjected to a transluminal coronary angioplasty, 245 patients were subjected to surgical revascularization and 341 patients were treated without revascularization. RESULTS: A total of 323 stenotic lesions (1.3 lesions per patient) were subjected to angioplasty. Angiographic success was obtained in 93% of patients. Angiographic success and lack of major complications such as death, infarction of the need for surgery, was obtained in 90% of patients. Five patients (2.1%) had a non fatal infarction and five required emergency surgery. Hospital mortality was 1.2%. During the year of follow up, 15% required a new revascularization, 3.3% had a non fatal infarction and 3.3% died. CONCLUSIONS: Coronary angioplasty had a 90% immediate success and 78% of patients were free of ischemic events after one year of follow up.

Both neuropeptide Y and serotonin are necessary for entrainment of circadian rhythms in mice by daily treadmill running schedules.

This study investigated the role of the suprachiasmatic nucleus (SCN) circadian pacemaker and its neuropeptide Y (NPY) and serotonin (5-HT) afferents in entrainment (synchronization) of mouse circadian rhythms by treadmill running. Blind C57BL/6j mice were run in treadmills for 3 hr/d for 3-10 weeks after receiving radio-frequency lesions of the SCN or the intergeniculate leaflet (IGL, the source of SCN NPY) or infusions of the 5-HT neurotoxin 5,7-DHT into the SCN area. Of 25 intact mice, 22 entrained and three showed period (tau, the mean duration of the circadian cycle) modulations to scheduled running. Arrhythmic SCN-ablated mice did not synchronize to scheduled running in a way suggestive of circadian pacemaker mediation. Of 15 mice with IGL lesions, only two with partial lesions entrained. Mice with complete IGL lesions (five), confirmed by immunocytochemistry, showed no entrainment or tau changes. Of 19 mice with 5-HT lesions, only two with partial lesions entrained. All but two mice with complete (10) or nearly complete (4) 5-HT denervation, confirmed by immunocytochemistry, showed tau modulations during the treadmill schedule. Failure to entrain was not explained by group differences in tau before the treadmill schedules. The results indicate that the SCN and both NPY and 5-HT are necessary for entrainment to 24 hr schedules of forced running but that complete loss of 5-HT does not prevent modulations of pacemaker motion by behavioral stimuli. Treadmill entrainment in mice may involve synergistic interactions between 5-HT and NPY afferents at some site within the circadian system.

Anticipation and entrainment to feeding time in intact and SCN-ablated C57BL/6j mice.

To characterize properties and mechanisms of non-photic entrainment of circadian rhythms, the effects of scheduled feeding were assessed in intact and suprachiasmatic nuclei (SCN) ablated C57BL/6j mice. During ad libitum food access, mice with no or partial SCN damage exhibited free-running activity and drinking rhythms, whereas mice with complete ablations were arrhythmic. When food was restricted to 4 h/day for 5-9 weeks, intact and partial SCN-ablated mice exhibited anticipatory activity to mealtime, concurrent with free-running rhythms. In some cases, free-running rhythms became entrained to feeding time; this was more prevalent in intact than partial ablated mice and was related to free-running period. Free-running phase or period were modified in other cases, revealing a phase-response profile consistent with other non-photic zeitgebers. Five of 12 mice with complete or near complete SCN ablations showed anticipatory activity. Mice that failed to anticipate were less active generally and sustained larger lesions. Sites of damage unique to non-anticipators were not evident. The results indicate that the SCN is not necessary for anticipatory rhythms in mice, but that cell populations distributed across several hypothalamic areas may be important for at least some behavioral markers of this circadian function.