After PCI and 6 to 18 mo of DAPT, clopidogrel reduced a composite of clinical events vs. aspirin at 6 y.

SOURCE CITATION: Kang J, Park KW, Lee H, et al. Aspirin versus clopidogrel for long-term maintenance monotherapy after percutaneous coronary intervention: The HOST-EXAM extended study. Circulation. 2023;147:108-17. 36342475.

In rheumatic heart disease-associated AF, rivaroxaban increased adverse vascular outcomes vs. VKA at 3 y.

SOURCE CITATION: Connolly SJ, Karthikeyan G, Ntsekhe M, et al. Rivaroxaban in rheumatic heart disease-associated atrial fibrillation. N Engl J Med. 2022;387:978-88. 36036525.

Starting and Sustaining an Extracorporeal Membrane Oxygenation Program.

The use of extracorporeal membrane oxygenation (ECMO) is growing rapidly in all patient populations, especially adults for both acute lung or heart failure. ECMO is a complex, high risk, resource-intense, expensive modality that requires appropriate planning, training, and management for successful outcomes. This article provides an optimal approach and the basic framework for initiating a new ECMO program, which can be tailored to meet local needs. Setting up a new ECMO program and sustaining it requires institutional commitment, physician champions, multidisciplinary team involvement, ongoing training, and education of the ECMO team personnel and a robust quality assurance program to minimize complications and improve outcomes.

Body temperature of free-ranging koalas (Phascolarctos cinereus) in south-east Queensland.

The distribution of the koala (Phascolarctos cinereus) in Queensland is predicted to contract as a result of climate change, driven by the frequency, intensity and duration of heatwaves and drought. However, little is known about the physiological responses of this species to environmental extremes under field conditions. This study aimed to establish the efficacy of surgically implanted thermal radio transmitters and data loggers to measure the body temperature of free-ranging koalas across a range of environmental conditions and ambient temperatures. Five free-ranging koalas in southeast Queensland were implanted with thermal transmitters and data loggers waxed together as a single package. Body temperatures were recorded for variable periods ranging from 3 to 12 months. Diurnal rhythms in body temperature were detected irrespective of season. The long-term diurnal body temperature peak for all koalas occurred between 16:00 and 17:00 h and body temperature was 36.7-36.9 °C, the long-term nadir occurred between 07:00 and 08:00 h and body temperature was 35.4-35.7 °C. Koala body temperatures as low as 34.2 °C and as high as 39.0 °C were recorded. Thermolability became apparent when ambient temperatures were outside the deduced thermal neutral zone for koalas (14.5-24.5 °C): heat was accumulated during the day and dissipated during the cool of the night. While this study is the first to report on body temperature of free-ranging koalas in their normal behavioural context, further investigations are necessary to determine the physiological boundaries of the thermal niche for this species, in order to better equip models that will more accurately predict the impacts of climate change on koalas.

Discrete or indiscrete? Redefining the colour polymorphism of the land snail Cepaea nemoralis.

Biologists have long tried to describe and name the different phenotypes that make up the shell polymorphism of the land snail Cepaea nemoralis. Traditionally, the view is that the ground colour of the shell is one of a few major colour classes, either yellow, pink or brown, but in practise it is frequently difficult to distinguish the colours, and define different shades of the same colour. To understand whether colour variation is in reality continuous, and to investigate how the variation may be perceived by an avian predator, we applied psychophysical models of colour vision to shell reflectance measures. We found that both achromatic and chromatic variation are indiscrete in Cepaea nemoralis, being continuously distributed over many perceptual units. Nonetheless, clustering analysis based on the density of the distribution did reveal three groups, roughly corresponding to human-perceived yellow, pink and brown shells. We also found large-scale geographic variation in the frequency of these groups across Europe, and some covariance between shell colour and banding patterns. Although further studies are necessary, the observation of continuous variation in colour is intriguing because the traditional theory is that the underlying supergene that determines colour has evolved to prevent phenotypes from "dissolving" into continuous trait distributions. The findings thus have significance for understanding the Cepaea polymorphism, and the nature of the selection that acts upon it, as well as more generally highlighting the need to measure colour objectively in other systems.

Recording body temperature in koalas (Phascolarctos cinereus): a comparison of techniques.

OBJECTIVE: Compare the use of four techniques to measure body temperature in koalas: intraperitoneal (thermal data logger and temperature sensitive radio transmitter), rectal (certified thermometer), tympanic (infrared thermometer), and hind foot (infrared camera). METHODS: The body temperature data collected concurrently from the intraperitoneal loggers were used as the benchmark in the analyses. RESULTS: The rectal, foot and tympanic methods consistently recorded lower body temperature when compared with the benchmark. There was a strong positive relationship (R2 = 0.79) between logger and rectal measurements, but no significant relationship between logger and foot or logger and tympanic measurements. CONCLUSION: Rectal measurements can be used to record internal body temperature, with the caveat that such measurements will generally register a temperature approximately 0.25°C lower than the actual intraperitoneal temperature.

Review: Vascular dementia: clinicopathologic and genetic considerations.

The incidence and severity of cerebrovascular disease (CVD) increase with advancing age, as does the risk of developing Alzheimer's disease (AD). Not surprisingly, heterogeneous forms of CVD may coexist with AD changes in the 'ageing brain'. These include angiopathies (affecting both large and small arteries) that result from 'classical' risk factors (hypertension, smoking and diabetes) and others (cerebral amyloid angiopathy) that are biochemically closely linked to AD. The morphologic consequences of these various vascular diseases are infarcts and/or haemorrhages of varying sizes within the brain, which lead to neurocognitive decline that may mimic AD - though the vascular abnormalities are usually detectable by neuroimaging. More subtle effects of CVD may include neuroinflammation and biochemical 'lesions' that have no reliable morphologic correlate and thus escape the attention of even an experienced Neuropathologist. The pathogenesis of hippocampal injury resembling ischaemic change - commonly seen in the brains of geriatric subjects - remains controversial. In recent years, genetically determined forms of microangiopathy (e.g. CADASIL, CARASIL, Trex1-related microangiopathies, CARASAL, familial forms of cerebral amyloid angiopathy or CAA) have provided interesting cellular and molecular clues to the pathogenesis of sporadic microvascular disease such as arteriolosclerosis and AD-related CAA.

Bis phenylene flattened 13-membered tetraamide macrocyclic ligand (TAML) for square planar cobalt(III).

The preparation, characterization, and evaluation of a cobalt(III) complex with 13-membered tetraamide macrocyclic ligand (TAML) is described. This is a square-planar (X-ray) S = 1 paramagnetic (1H NMR) compound, which becomes an S = 0 diamagnetic octahedral species in excess d5-pyridine. Its one-electron oxidation at an electrode is fully reversible with the lowest E 1/2 value (0.66 V vs SCE) among all investigated CoIII TAML complexes. The oxidation results in a neutral blue species which is consistent with a CoIII/radical-cation ligand. The ease of oxidation is likely due to the two benzene rings incorporated in the ligand structure (whereas there is just one in many other CoIII TAMLs). The oxidized neutral species are unexpectedly EPR silent, presumably due to the π-stacking aggregation. However, they display eight-line hyperfine patterns in the presence of excess of 4-tert-butylpyridine or 4-tert-butyl isonitrile. The EPR spectra are more consistent with the CoIII/radical-cation ligand formulation rather than with a CoIV complex. Attempts to synthesize a similar vanadium complex under the same conditions as for cobalt using [VVO(OCHMe2)3] were not successful. TAML-free decavanadate was isolated instead.

Leptospira interrogans serogroup Pomona infections in the UK: is there a real threat for farm animals?

Current typing of Leptospira strains requires a combination of both serological and molecular methods. Study of the epidemiology of strains within the Pomona serogroup has proved problematic due to the limitations of serological typing methods. This is particularly true of the two main complexes within this group, namely the Pomona, Monjakov, Kennewicki cluster in Leptospira interrogans species and the Mozdok, Tsaratsovo, Kunming, Altodouro cluster in Leptospira kirschneri Strains from the south of England have been shown previously to belong to L kirschneri serovar Mozdok, strains of which are maintained by small rodents in western Europe. While they may occasionally cause disease in domestic animals, they are unlikely to be of economic importance. In contrast, L interrogans serovar Pomona type Kennewicki strains have been shown to be significant animal pathogens, especially in north America, while L interrogans serovar Pomona types Pomona and Monjakov have not been associated with significant economic loss. The purpose of this study was to examine 10 UK serovar Pomona isolates to assess type as a means of assessing the possible risk they pose to British livestock. All isolates were identified as L interrogans serovar Pomona type Pomona and were therefore unlikely to pose a significant threat to domestic animals in the UK.

Elevated pCO2 affects tissue biomass composition, but not calcification, in a reef coral under two light regimes.

Ocean acidification (OA) is predicted to reduce reef coral calcification rates and threaten the long-term growth of coral reefs under climate change. Reduced coral growth at elevated pCO2 may be buffered by sufficiently high irradiances; however, the interactive effects of OA and irradiance on other fundamental aspects of coral physiology, such as the composition and energetics of coral biomass, remain largely unexplored. This study tested the effects of two light treatments (7.5 versus 15.7 mol photons m-2 d-1) at ambient or elevated pCO2 (435 versus 957 µatm) on calcification, photopigment and symbiont densities, biomass reserves (lipids, carbohydrates, proteins), and biomass energy content (kJ) of the reef coral Pocillopora acuta from Kane'ohe Bay, Hawai'i. While pCO2 and light had no effect on either area- or biomass-normalized calcification, tissue lipids gdw-1 and kJ gdw-1 were reduced 15% and 14% at high pCO2, and carbohydrate content increased 15% under high light. The combination of high light and high pCO2 reduced protein biomass (per unit area) by approximately 20%. Thus, under ecologically relevant irradiances, P. acuta in Kane'ohe Bay does not exhibit OA-driven reductions in calcification reported for other corals; however, reductions in tissue lipids, energy content and protein biomass suggest OA induced an energetic deficit and compensatory catabolism of tissue biomass. The null effects of OA on calcification at two irradiances support a growing body of work concluding some reef corals may be able to employ compensatory physiological mechanisms that maintain present-day levels of calcification under OA. However, negative effects of OA on P. acuta biomass composition and energy content may impact the long-term performance and scope for growth of this species in a high pCO2 world.

Leptospira interrogans serovars Bratislava and Muenchen animal infections: Implications for epidemiology and control.

Strains of Leptospira interrogans belonging to two very closely related serovars - Bratislava and Muenchen - have been associated with disease in domestic animals, in particular pigs, but also in horses and dogs. Similar strains have also been recovered from various wildlife species. Their epidemiology is poorly understood. Two hundred and forty seven such isolates, from UK domestic animal and wildlife species, were examined by restriction endonuclease analysis in an attempt to elucidate their epidemiology. A representative sub-sample of 65 of these isolates was further examined by multiple-locus variable-number tandem repeat analysis and 22 by secY sequencing. Ten restriction pattern types were identified. The majority of isolates fell into one of three restriction endonuclease analysis pattern types designated B2a, B2b and M2a. B2a was ubiquitous and was isolated from 10 species and represented the majority of the horse and all dog isolates. B2b was very different, being isolated only from pigs, indicating that this type was maintained by pigs. The pattern M2a was reported for the majority of isolates from pigs but also was common in small rodents isolates. Five restriction pattern types were found only in wildlife suggesting that they are unlikely to pose a disease threat to domestic animals. Multiple-locus variable-number tandem repeat analysis identified six clusters. The REA types B2a and B2b were all found in one MLVA cluster while the majority of the M2a strains examined occurred in another cluster. The secY sequencing detected only one sequence type, clustered with other serovars of Leptospira interrogans.

Prognostic value of Ki67 in localized prostate carcinoma: a multi-institutional study of >1000 prostatectomies.

BACKGROUND: Expanding interest in and use of active surveillance for early state prostate cancer (PC) has increased need for prognostic biomarkers. Using a multi-institutional tissue microarray resource including over 1000 radical prostatectomy samples, we sought to correlate Ki67 expression captured by an automated image analysis system with clinicopathological features and validate its utility as a clinical grade test in predicting cancer-specific outcomes. METHODS: After immunostaining, the Ki67 proliferation index (PI) of tumor areas of each core (three cancer cores/case) was analyzed using a nuclear quantification algorithm (Aperio). We assessed whether Ki67 PI was associated with clinicopathological factors and recurrence-free survival (RFS) including biochemical recurrence, metastasis or PC death (7-year median follow-up). RESULTS: In 1004 PCs (∼4000 tissue cores) Ki67 PI showed significantly higher inter-tumor (0.68) than intra-tumor variation (0.39). Ki67 PI was associated with stage (P<0.0001), seminal vesicle invasion (SVI, P=0.02), extracapsular extension (ECE, P<0.0001) and Gleason score (GS, P<0.0001). Ki67 PI as a continuous variable significantly correlated with recurrence-free, overall and disease-specific survival by multivariable Cox proportional hazard model (hazards ratio (HR)=1.04-1.1, P=0.02-0.0008). High Ki67 score (defined as ⩾5%) was significantly associated with worse RFS (HR=1.47, P=0.0007) and worse overall survival (HR=2.03, P=0.03). CONCLUSIONS: In localized PC treated by radical prostatectomy, higher Ki67 PI assessed using a clinical grade automated algorithm is strongly associated with a higher GS, stage, SVI and ECE and greater probability of recurrence.

Surgical implantation of temperature-sensitive transmitters and data-loggers to record body temperature in koalas (Phascolarctos cinereus).

BACKGROUND: Under predicted climate change scenarios, koala distribution in Australia is expected to be adversely affected. Recent studies have attempted to identify suitable habitat, based on models of bioclimatic regions, but to more accurately reflect the thermal tolerance and behavioural adaptations of the various regional populations, the koala's response to periods of heat stress will need to be investigated at the individual animal level. OBJECTIVE: To explore the safety and suitability of temperature-sensitive intra-abdominal implants for monitoring core body temperature in the koala. METHODS: A temperature-sensitive radio transmitter and thermal iButton data-logger, waxed together as a package, were surgically implanted into the abdominal cavity of four captive koalas. In one animal the implant was tethered and in the other three, it was left free-floating. RESULTS: After 3 months, the implants were removed and all four koalas recovered without complications. The tethering of the package in the one koala resulted in minor inflammation and adhesion, so this practice was subsequently abandoned. The free-floating deployments were complication-free and revealed a diurnal body temperature rhythm, with daily ranges of 0.4-2.8°C. The minimum recorded body temperature was 34.2°C and the maximum was 37.7°C. The difference in the readings obtained from the transmitters and iButtons never exceeded 0.3°C. CONCLUSIONS: The suitability of the surgical approach was confirmed, from both the animal welfare and data collection points of view.

Stereocomplexed poly(limonene carbonate): a unique example of the cocrystallization of amorphous enantiomeric polymers.

We report the cocrystallization of the regio- and stereoregular chiral copolymer poly(limonene carbonate). To the best of our knowledge, this marks the first example of an amorphous, enantiomerically pure polymer that becomes crystalline upon stereocomplexation with its complementary enantiomer. By analyzing X-ray powder diffraction data, we propose a packing model in which sheets of enantiopure chains interdigitate with layers of the opposite enantiomer, forming a "steric zipper".

Recent Advances in Pediatric Cardiopulmonary Bypass.

There have been numerous recent advances geared specifically toward the practice of pediatric cardiopulmonary bypass (CPB). These advances include the development of the first oxygenator intended solely for the neonatal CPB patient; pediatric oxygenators with low prime volumes and surface areas, which allow flows up to 2 L/min; pediatric oxygenators with integrated arterial filters; and miniature ultrafiltration (UF) devices, which allow for high rates of ultrafiltrate removal. When used in combination with heart lung machines with mast-mounted pumps, these advances can result in significant decreases in CPB circuit surface areas and prime volumes. This may attenuate CPB-associated hemodilution and decrease or eliminate the need for homologous red blood cells during or after CPB. In addition to these equipment-related advances, changes in myocardial protection strategies and the technique of modified UF as it relates to these advances are discussed.

One-way valve malfunction in an extracorporeal membrane oxygenation priming circuit.

Developing technologies have changed both the components and the management style when extracorporeal membrane oxygenation (ECMO) is used to support critically ill cardiac and respiratory patients. The Cardiohelp system is a small, portable extracorporeal system just recently available within the United States. Manufacturing standards and quality processes have made mechanical failure and malfunction of extracorporeal components less common; however, there is still potential for mechanical failure or component malfunction before or during extracorporeal support. This case review describes the malfunction of a Retroguard unidirectional flow valve integrated into the priming setup of a Cardiohelp system during the priming process.

'Leptorapide' - a one-step assay for rapid diagnosis of human leptospirosis.

SUMMARY: Leptospirosis is a globally important zoonotic infection caused by spirochaetes of the genus Leptospira. It is transmitted to humans by direct contact with infected animals or indirectly via contaminated water. It is mainly a problem of the resource-poor developing countries of the tropical and sub-tropical regions of the world but outbreaks due to an increase in travel and recreational activities have been reported in developed and more industrialized areas of the world. Current methods of diagnosis are costly, time-consuming and require the use of specialized laboratory equipment and personnel. The purpose of this paper is to report the validation of the 'Leptorapide®' test (Linnodee Ltd, Northern Ireland) for the diagnosis of human leptospirosis. It is a simple one-step latex agglutination assay performed using equal volumes of serum sample and antigen-bound latex beads. Evidence of leptospiral antibodies is determined within minutes. Agglutination is scored on a scale of 1-5 and the results interpreted using a score card provided with the kit. Validation has been performed with a large sample size obtained from individuals originating from various parts of the world including Brazil and India. The test has shown sensitivity and specificity values of 97·1% and 94·0%, respectively, relative to the microscopic agglutination test. The results demonstrate that Leptorapide offers a cost-effective and accurate alternative to the more historical methods of antibody detection.