Integration of palliative care consultation into the management of patients with chronic limb-threatening ischemia.

OBJECTIVE: We assessed the feasibility of integrating palliative care consultation into the routine management of patients with chronic limb-threatening ischemia (CLTI). Additionally, we sought to describe patient-reported outcomes from the palliative care and vascular literature in patients with CLTI receiving a palliative care consultation at our institution. METHODS: This was a single-institution, prospective, observational study that aimed to assess feasibility of incorporating palliative care consultation into the management of patients admitted to our tertiary academic medical center with CLTI by looking at utilization of palliative care before and after implementation of a protocol-based palliative care referral system. A survey comprised of patient-reported outcomes from the palliative care literature was administered to patients before and after palliative consultation. Length of stay and mortality were compared between our study cohort and a historic cohort of patients admitted with CLTI. RESULTS: Over a 14-month enrollment period, 44% of patients (n = 39) with CLTI (rest pain, 36%; tissue loss, 64%) admitted to the vascular service received palliative care consultation, compared with 5% of patients (n = 4) who would have met criteria over the preceding 14 months before our protocol was instituted. The mean age was 69 years, 23% were female, 92% were white, and 49% were able to ambulate independently. Revascularization included bypass (46%), peripheral vascular intervention (23%), and femoral endarterectomy (21%). Additional procedures included minor amputation or wound debridement (26%) and major amputation (15%). No patients received medical management alone. After receiving palliative care consultation, patients reported experiencing less emotional distress than before consultation (P = .03). They also reported being less bothered by uncertainty regarding what to expect from the course of their illness (P = .002). Fewer patients reported being unsure of the purpose of their medical care after palliative care consultation (8%) vs before (18%), although this was not statistically significant (P = .10). Median length of stay was longer in the study group compared with the historic cohort (8 vs 7 days; P = .02). There was no difference in 30-day mortality (3% vs 8%; P = .42) between the study group and the historic cohort (n = 77). CONCLUSIONS: Integrating inpatient palliative care consultation into the routine management of patients with CLTI is feasible and may improve emotional domains of health-related quality of life. This study laid the foundation for future studies on longer term outcomes of patients with CLTI undergoing palliative care consultation as well as the benefit of outpatient palliative care consultation in patients with CLTI.

MRI-based 3-dimensional volumetric assessment of fatty infiltration and muscle atrophy in rotator cuff tears.

BACKGROUND: The Goutallier and Warner Classification systems are useful in determining rotator cuff reparability. Data are limited on how accurately the scapular-Y view used in both systems reflects the 3-dimensional (3-D) changes in fatty infiltration (FI) and muscle atrophy (MA). Tendon retraction in the setting of a cuff tear may also influence the perception of these changes. This study's objectives were to (1) measure the 3-D volume of the supraspinatus muscle in intact rotator cuffs, and with varying magnitudes of retraction; (2) measure the 3-D volume of FI in the supraspinatus muscle in these conditions; and (3) determine the influence of tendon retraction on measured FI and MA using the Goutallier and Warner Classification Systems. METHODS: Between August 2015 and February 2016, all shoulder magnetic resonance images (MRIs) at the Portland VA Medical Center were standardized to include the medial scapular border. MRIs and charts were reviewed for inclusion/exclusion criteria. Included MRIs were categorized into 4 groups based on rotator cuff retraction. Supraspinatus muscle and fossa were traced to create 3-D volumes. FI and MA were measured within the supraspinatus. The supraspinatus muscle was graded among 6 physicians using the Goutallier and Warner classification systems. These grades were compared to 3-D measured FI and MA. The influence of tendon retraction on the measured grades were also evaluated. RESULTS: One hundred nine patients met inclusion/exclusion criteria. Ten MRIs for each group (N = 40) were included for image analysis. Supraspinatus volume tracings were highly reproducible and consistent between tracers. Supraspinatus muscle volumes decreased while global FI and MA increased with greater degrees of tendon retraction. In muscles with less than 10% global fat, fat concentrated in the lateral third of the muscle. In muscle with more than 10% global fat content, it distributed more diffusely throughout the muscle from medial to lateral. In comparing the scapular-Y to a medial cut, there was no consistent trend in FI whereas MA was more accurate at the medial cut. CONCLUSION: Parasagittal imaging location did not significantly influence the Goutallier score; however, assessment of MA using the Warner score leads readers to perceive less MA medially regardless of the magnitude of tendon retraction. The pattern of FI within the supraspinatus muscle changes from a laterally based location around the muscle-tendon junction to a more diffuse, global infiltration pattern when the whole muscle fat content exceeds 10%.

Cognitive performance in midlife type 2 diabetes: results from the ENBIND study.

AIMS: To establish the impact of uncomplicated type 2 diabetes on cognitive and neuropsychological performance in midlife. METHODS: We performed a cross-sectional study of middle-aged adults with uncomplicated type 2 diabetes and a cohort of healthy control participants. General cognition was assessed using the Montreal Cognitive Assessment test and neuropsychological assessment was undertaken using a detailed neuropsychological assessment battery. RESULTS: A total of 152 participants (102 with type 2 diabetes and 50 controls) were recruited (mean age 52 ± 8 years, 51% women). Participants with midlife type 2 diabetes were more than twice as likely to make an error on the Montreal Cognitive Assessment test [incidence rate ratio 2.44 (95% CI 1.54 to 3.87); P < 0.001]. Further, type 2 diabetes was also associated with significantly lower memory composite score [ß: -0.20 (95% CI -0.39 to -0.01); P = 0.04] and paired associates learning score [ß: = -1.97 (95% CI -3.51, -0.43); P = 0.01] on the neuropsychological assessment battery following adjustment for age, sex, BMI, educational attainment and hypercholesterolaemia. CONCLUSIONS: Even in midlife, type 2 diabetes was associated with small but statistically significant cognitive decrements. These statistically significant decrements, whilst not clinically significant in terms of objective cognitive impairment, may have important implications in selecting out individuals most at risk of later cognitive decline for potential preventative interventions in midlife.

Characterization of a G-Quadruplex Structure in Pre-miRNA-1229 and in Its Alzheimer's Disease-Associated Variant rs2291418: Implications for miRNA-1229 Maturation.

Alzheimer's disease (AD), the most common age-related neurodegenerative disease, is associated with various forms of cognitive and functional impairment that worsen with disease progression. AD is typically characterized as a protein misfolding disease, in which abnormal plaques form due to accumulation of tau and ß-amyloid (Aß) proteins. An assortment of proteins is responsible for the processing and trafficking of Aß, including sortilin-related receptor 1 (SORL1). Recently, a genome-wide association study of microRNA-related variants found that a single nucleotide polymorphism (SNP) rs2291418 within premature microRNA-1229 (pre-miRNA-1229) is significantly associated with AD. Moreover, the levels of the mature miRNA-1229-3p, which has been shown to regulate the SORL1 translation, are increased in the rs2291418 pre-miRNA-1229 variant. In this study we used various biophysical techniques to show that pre-miRNA-1229 forms a G-quadruplex secondary structure that coexists in equilibrium with the canonical hairpin structure, potentially controlling the production of the mature miR-1229-3p, and furthermore, that the AD-associated SNP rs2291418 pre-miR-1229 changes the equilibrium between these structures. Thus, the G-quadruplex structure we identified within pre-miRNA-1229 could potentially act as a novel therapeutic target in AD.

Thoracic kyphosis assessment in postmenopausal women: an examination of the Flexicurve method in comparison to radiological methods.

The Flexicurve ruler is an alternative method to radiographs for measuring thoracic kyphosis (curvature), but it is not certain that it is comparable. This study shows that Flexicurve can estimate radiographic vertebral centroid angles with less error than Cobb angles but that its accuracy would be inadequate for most clinical purposes. INTRODUCTION: The Flexicurve ruler provides a non-radiological method of measuring thoracic kyphosis (TK) that has moderately strong correlations with the gold-standard radiographic Cobb angle method, while consistently underestimating the TK angle. Cobb angles can include measurement errors that may contribute to poor agreement, particularly in older populations. The vertebral centroid angle could be a better radiographic reference method for the validation of Flexicurve. Using two separate radiographic measurements of TK, we examined the validity of Flexicurve. We aimed to ascertain the level of agreement between measures and to empirically explore reasons for between-method differences. METHODS: TK angles determined using Flexicurve and radiographic Cobb and vertebral centroid methods were compared using data from 117 healthy postmenopausal women (mean (SD) age 61.4 (7.0) years). Bland and Altman plots were used to assess differences between methods. Age, bone mineral density and body mass index were examined as characteristics that might explain any differences. RESULTS: Flexicurve angles were scaled prior to analysis. There was no statistically significant difference between angles produced by Flexicurve and vertebral centroid methods (MD - 2.16°, 95%CI - 4.35° to 0.03°) although differences increased proportionally with TK angles. Flexicurve angles were significantly smaller than radiographic Cobb angles and depending on the scaling method used, systematic error ranged between - 2.48° and - 5.19°. Age accounts for some of the differences observed (R2 < 0.08, p < 0.005). CONCLUSIONS: TK measured using the Flexicurve shows better agreement with the radiographic vertebral centroid method, but inaccuracy of the Flexicurve increases with increasing angle of kyphosis.

Integration between swim speed and mouth size evolves repeatedly in Trinidadian guppies and aligns with suction-feeding fishes.

Well-supported correlations between swim speed and mouth size during prey capture suggest the broad existence of an integrated relationship between locomotion and feeding in suction-feeding fishes. However, the influence of specialization on this relationship is unclear. We used divergent populations of Trinidadian guppies (Poecilia reticulata) to test whether integration during suction is generalizable to a non-suction specialist and whether intraspecific specialization of component systems affects their integration. Guppies from replicate high- and low-predation streams were recorded capturing wild-type zooplankton using suction. Alternative general linear models supported a positive correlation between swim speed and mouth size in derived low-predation populations, suggesting that the relationship can be extended in some cases. High-predation populations lack this integration, which may be the result of direct selection or constraints imposed by selection on locomotion. As guppies invade new habitats they may be evolving a new, integrated performance phenotype from a non-integrated ancestor.

Janus kinase inhibition suppresses PKC-induced cytokine release without affecting HIV-1 latency reversal ex vivo.

BACKGROUND: Despite the durable viral suppression afforded by antiretroviral therapy, HIV-1 eradication will require strategies to target latently infected cells that persist in infected individuals. Protein kinase C (PKC) activation is a promising strategy to reactivate latent proviruses and allow for subsequent recognition and clearance of infected cells by the immune system. Ingenol derivatives are PKC agonists that induce latency reversal but also lead to T cell activation and the release of pro-inflammatory cytokines, which would be undesirable in vivo. In this work, we sought to identify compounds that would suppress pro-inflammatory cytokine production in the context of PKC activation. DESIGN AND METHODS: We performed an in vitro screen to identify compounds that could dampen pro-inflammatory cytokine release associated with T cell activation, using IL-6 as a model cytokine. We then tested the ability of the most promising screening hit, the FDA-approved Janus Kinase (JAK) inhibitor ruxolitinib, to diminish release of multiple cytokines and its effect on latency reversal using cells from HIV-1-positive, aviremic participants. RESULTS: We demonstrate that co-administration of ruxolitinib with ingenol-3,20-dibenzoate significantly reduces pro-inflammatory cytokine release without impairing latency reversal ex vivo. CONCLUSION: The combination of ingenol compounds and JAK inhibition represents a novel strategy for HIV-1 eradication.

DNA transfer through nonintimate social contact.

The UK and Ireland Association of Forensic Science Providers' (AFSP) Body Fluid Forum (BFF) set out to assist in the interpretation of sexual offence cases where semen is absent on vaginal swabs but female DNA is present on penile swabs or male underwear, and the issue to be addressed is whether or not sexual intercourse occurred. This study aims to investigate the frequency and amount of female DNA transferred to the penis and underwear of males following staged nonintimate social contact with females and to compare the findings with the amount of female DNA transferred to the penis and subsequently to the underwear of a male who had engaged in unprotected sexual intercourse with a female. In this study, no matching female DNA was detected on the inside front of the 44 items of male underwear used in this research following staged contact of a nonintimate nature and subsequent secondary transfer to the penis. After sexual intercourse, full profiles matching the female participant were found on the inside front of the males underwear with maximum peak heights in the range between 1898 and 3157 rfu. It was possible to demonstrate that DNA can occasionally transfer to the waistband and outside front of underwear worn by a male following staged nonintimate social contact. Data obtained in this study suggest that a matching female DNA profile below a peak height of 1000 rfu on the waistband of a male's underwear might be explained by nonintimate social contact with secondary transfer of female DNA from the male's hands.

Belongingness in the workplace: a study of Malaysian nurses' experiences.

BACKGROUND: The need to belong has been proposed as the most basic need for human psychological well-being. Lack of belongingness has been associated with stress, anxiety and lack of esteem. Social and psychological functioning in the workplace has been linked to nurses' interconnection with others and their perceptions of belongingness. AIM: To explore factors contributing to Malaysian nurses' sense of belonging in the workplace. METHODS: A descriptive questionnaire survey of registered nurses (n = 437) working in two Malaysian hospitals was conducted in 2011. Previously validated questionnaires translated into the Malay language were used. Data were analysed using SPSS 19.0. RESULTS: Nurses enhanced their sense of belonging through acceptance, 'fitting in', respect and group harmony. There were no specific demographic factors contributing to the nurses' perceptions. The findings suggest that these priorities for belongingness were contextually influenced by factors such as elements of Malaysian culture, the nature of nurses' teamwork and stereotypical values on the nursing profession. LIMITATIONS: Data were collected in only two hospitals. Experiences of nurses in other hospitals and areas of Malaysia may not be similar. The influence of Malaysian culture in this study raises issues about utilization of a measurement scale developed in Western cultures, which may not directly accord with cultural values of an Eastern ethnicity. CONCLUSIONS: Aspects of belongingness in Malaysian nurses reflect those of nurses elsewhere. However, there are specific cultural influences at play. Therefore, development of a measurement scale based on Eastern culture would help in increasing understanding of workplace practices among these groups. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Workplaces that perpetuate an environment that is not conducive to generating a sense of belonging may have an untoward impact on care delivery. Healthcare policies need to ensure patient care has a focus on engaging practitioners within multidisciplinary teams.

Scoping the context of programs and services for maintaining wellness of older people in rural areas of Indonesia.

INTRODUCTION: Ageing and problems concerning the aged are an increasing and concerning reality in developing and underdeveloped countries such as Indonesia. Improving service quality is important to promote and maintain wellness of older persons, especially in rural areas. AIM: To explore programs and services offered to the elderly in a rural area of Indonesia to support them in promoting and maintaining their wellness. To describe roles and practices of health professionals and teams responsible for delivering services to older people. METHODS: Action research was used with mixed method data collection (interview and survey). RESULTS: Results demonstrated that activities related to the elderly health programs were limited due to budget and facilities. Practices of health staff for elderly in the community focused on intervention tasks, rather than prevention. LIMITATION: Lack of available information on the range of programs and services implemented in Indonesia for the elderly in community settings was a limitation of this study. CONCLUSION: Programs and services for older people have been implemented in Indonesia. However, these do not yet meet their needs, especially in rural areas. There is a need for greater focus on health promotion and illness prevention. IMPLICATION FOR NURSING AND HEALTH POLICY: Findings contribute to development of international knowledge in community health nursing, as these issues may not be only relevant to Indonesia. It is timely for governments, including in Indonesia, to evaluate health workforce needs in the community and appropriate educational qualifications for delivering optimal health services for older people.

Technologies for the discovery of G protein-coupled receptor-targeting biologics.

G protein-coupled receptors (GPCRs) are important pharmaceutical targets, working as entry points for signaling pathways involved in metabolic, neurological, and cardiovascular diseases. Although small molecules remain the major GPCR drug type, biologic therapeutics, such as peptides and antibodies, are increasingly found among clinical trials and Food and Drug Administration (FDA)-approved drugs. Here, we review state-of-the-art technologies for the engineering of biologics that target GPCRs, as well as proof-of-principle technologies that are ripe for this application. Looking ahead, inexpensive DNA synthesis will enable the routine generation of computationally predesigned libraries for use in display assays for the rapid discovery of GPCR binders. Advances in synthetic biology are enabling the increased throughput of functional GPCR assays to the point that they can be used to directly identify biologics that modulate GPCR activity. Finally, we give an overview of adjacent technologies that are ripe for application to discover biologics that target human GPCRs.

Does home blood pressure monitoring improve blood pressure-related outcomes in people living with chronic kidney disease? A systematic review.

High blood pressure is an important risk factor for cardiovascular disease and disease progression in chronic kidney disease (CKD). Evidence on the effects of home blood pressure monitoring (HBPM) is limited. This review aimed to determine the effect of HBPM on systolic (SBP) and diastolic blood pressure (DBP) in patients with CKD. We searched medical literature databases for eligible studies presenting pre- and post-data for interventions utilizing HBPM. Study quality was assessed using the NHLBI tools for quality assessment. Heterogeneity prohibited a meta-analysis so estimates of effects were calculated along a sign test to examine the probability of observing the given pattern of positive effect direction. Eighteen studies were included (n = 1187 participants, mean age 56.7 [± 7.7] years). In 15 studies, HBPM was conducted within the context of additional high-level tailored support. Overall, the quality of n = 7/18 studies was rated as "good"; n = 6/18 were "fair," and n = 5/18 were rated as "poor." Interventions utilizing HBPM had a significant effect on SBP, with 14/16 studies favoring the intervention (88% [95% CI: 62%-98%], P = .002). Favorable effects were also seen on DBP (73% [95% CI: 45%-92%], P = .059). HBPM had a favorable effect on blood pressure goal attainment (86% [95% CI: 42%-100%], P = .062). HBPM in patients with CKD as part of a multicomponent intervention may lead to clinically significant reductions in blood pressure; however, research is needed to support the validity of this claim due to the high heterogeneity across the studies included.

Facilitators and barriers to adolescent participation in a TB clinical trial.

The inclusion of adolescents in TB drug trials is essential for the development of safe, child-friendly regimens for the prevention and treatment of TB. TB Trials Consortium Study 31/AIDS Clinical Trials Group A5349 (S31/A5349) enrolled adolescents as young as 12 years old. We assessed investigator and coordinator described facilitators and barriers to adolescent recruitment, enrollment, and retention.Interviews were conducted with six investigators from sites that enrolled adolescent participants and six investigators from non-enrolling sites. Additionally, two focus groups were conducted with study coordinators from enrolling sites and two focus groups with non-enrolling sites. Discussions were transcribed, analyzed, summarized, and summaries were reviewed by Community Research Advisors Group members and research group representatives for content validity.Investigators and coordinators attributed the successful enrollment of adolescents to the establishment and cultivation of external partnerships, flexibility to accommodate adolescents' schedules, staff engagement, recruitment from multiple locations, dedicated recruitment staff working onsite to access potential participants, creation of youth-friendly environments, and effective communications. Non-enrolling sites were mainly hindered by regulations. Suggestions for improvement in future trials focused on study planning and site preparations.Proactive partnerships and collaboration with institutions serving adolescents helped identify and reduce barriers to their inclusion in this trial..

Use of hare bone for the manufacture of a Clovis bead.

A tubular bone bead dating to ~ 12,940 BP was recovered from a hearth-centered activity area at the La Prele Mammoth site in Converse County, Wyoming, USA. This is the oldest known bead from the Western Hemisphere. To determine the taxonomic origin of the bead, we extracted collagen for zooarchaeology by mass spectrometry (ZooMS). We also used micro-CT scanning for morphological analysis to determine likely skeletal elements used for its production. We conclude that the bead was made from a metapodial or proximal phalanx of a hare (Lepus sp.). This find represents the first secure evidence for the use of hares during the Clovis period. While the use of hare bone for the manufacture of beads was a common practice in western North America during the Holocene, its origins can now be traced back to at least the terminal Pleistocene.

Addressing the needs of people with extensively drug-resistant TB through pre-approval access to drugs and research.

Multiple therapeutic options exist for people with drug-resistant TB (DR-TB), but there is an urgent need to improve access to novel compounds and regimens for people with difficult to treat forms of TB. In additional to formal research studies and clinical trials, other mechanisms of accessing promising new TB compounds need to be introduced as soon as these drugs have shown efficacy and safety in phase II trials. Pre-approval access programs for newer TB drugs such as bedaquiline, delamanid, and pretomanid all suffered from shortcomings. These can be addressed for the next generation of new TB drugs through a series of concerted actions by stakeholders at multiple levels. In this viewpoint, we advocate for transparent, accessible pre-approval access as a core element of person-centered care for DR-TB.

Il existe de nombreuses options thérapeutiques pour les personnes atteintes de TB résistante aux médicaments (DR-TB), mais il est urgent d'améliorer l'accès aux nouvelles molécules et aux nouveaux schémas thérapeutiques pour les personnes atteintes de formes de TB difficiles à traiter. Outre les études de recherche formelles et les essais cliniques, d'autres mécanismes d'accès aux nouvelles molécules prometteuses contre la TB doivent être mis en place dès que ces médicaments ont démontré leur efficacité et leur innocuité lors des essais de phase II. Les programmes d'accès avant approbation pour les nouveaux médicaments contre la TB tels que la bédaquiline, le delamanid et le pretomanid ont tous souffert de lacunes. Ces problèmes peuvent être résolus pour la prochaine génération de nouveaux médicaments contre la TB grâce à une série d'actions concertées entre les parties prenantes à différents niveaux. Dans cette optique, nous préconisons un accès transparent et accessible avant approbation, en tant qu'élément central des soins centrés sur la personne pour la DR-TB.

Shorter TB treatment regimens should be safer as well.

Most ongoing and planned TB therapeutic trials are focused on shortening the duration of treatment while giving less consideration to other aspects of TB care that are important to people with TB. Here we argue that other variables besides duration of TB treatment should also be considered when developing new TB treatment regimens, including drug toxicity, time spent in monitoring and overall quality of life while on therapy. We examine the specific use of linezolid in treatment-shortening trials for drug-susceptible TB and propose additional endpoints that should be prioritised in TB treatment studies.

La majorité des essais thérapeutiques en cours et prévus sur la TB se concentrent sur la réduction de la durée du traitement tout en accordant moins d'attention à d'autres aspects des soins de la TB qui sont importants pour les personnes atteintes de la TB. Nous soutenons ici que d'autres variables que la durée du traitement de la TB devrait également être prises en compte lors de l'élaboration de nouveaux schémas thérapeutiques, notamment la toxicité des médicaments, le temps passé à la surveillance et la qualité de vie globale pendant le traitement. Nous examinons l'utilisation spécifique du linézolide dans les essais de raccourcissement du traitement de la TB sensible aux médicaments et proposons des critères d'évaluation supplémentaires qui devraient être prioritaires dans les études sur le traitement de la TB.

Best practices for the care of pregnant people living with TB.

BACKGROUND: Each year more than 200,000 pregnant people become sick with TB, but little is known about how to optimize their diagnosis and therapy. Although there is a need for further research in this population, it is important to recognize that much can be done to improve the services they currently receive.METHODS: Following a systematic review of the literature and the input of a global team of health professionals, a series of best practices for the diagnosis, prevention and treatment of TB during pregnancy were developed.RESULTS: Best practices were developed for each of the following areas: 1) screening and diagnosis; 2) reproductive health services and family planning; 3) treatment of drug-susceptible TB; 4) treatment of rifampicin-resistant/multidrug-resistant TB; 5) compassionate infection control practices; 6) feeding considerations; 7) counseling and support; 8) treatment of TB infection/TB preventive therapy; and 9) research considerations.CONCLUSION: Effective strategies for the care of pregnant people across the TB spectrum are readily achievable and will greatly improve the lives and health of this under-served population.

One size does not fit all: community views on choices for TB treatment and prevention.

Treatment and prevention paradigms in TB have been dominated by a 'one-size-fits-all' approach, in which all persons are given the same treatment regimens. This stands in contrast to other health conditions, where differentiated models of care have been shown to be effective. In this Viewpoint, we make the case for considering multiple factors when deciding which regimens should be offered to people with TB infection and disease. Choice about which regimens to use should be made in conjunction with people who have TB and consider efficacy, safety, duration, pill burden, formulation, drug interactions, time spent in monitoring, drug susceptibility, compatibility with other areas of life, and availability of support services. Ideally, these choices should be considered within an equity framework with the most intensified services being offered to those considered most vulnerable.

Les paradigmes de traitement et de prévention de la TB ont été dominés par une approche « unique ¼, dans laquelle toutes les personnes reçoivent les mêmes schémas thérapeutiques. Cette approche contraste avec d'autres problèmes de santé, pour lesquels des modèles de soins différenciés se sont avérés efficaces. Dans ce point de vue, nous plaidons en faveur de la prise en compte de multiples facteurs au moment de décider des schémas thérapeutiques à proposer aux personnes atteintes de infection tuberculeuse et de TB maladie. Le choix des traitements doit être fait en collaboration avec les personnes atteintes de TB et tenir compte de l'efficacité, de l'innocuité, de la durée, du nombre de comprimés, de la formulation, des interactions médicamenteuses, du temps consacré à la surveillance, de la sensibilité aux médicaments, de la compatibilité avec d'autres domaines de la vie et de la disponibilité des services d'aide. Idéalement, ces choix devraient être envisagés dans un cadre d'équité, les services les plus intensifs étant proposés aux personnes considérées comme les plus vulnérables.

Aortic dissection detection and thrombus structure quantification using volumetric ultrasound, histology, and scanning electron microscopy.

Aortic dissection occurs when a weakened portion of the intima tears, and a separation of layers propagates along the aortic wall to form a false lumen filled with active blood flow or intramural thrombus. The unpredictable nature of aortic dissection formation and need for immediate intervention leaves limited serial human image data to study the formation and morphological changes that follow dissection. We used volumetric ultrasound examination, histology, and scanning electron microscopy (SEM) to examine intramural thrombi at well-defined timepoints after dissection occurs in apolipoprotein E-deficient mice infused with angiotensin II (n = 71). Stratification of red blood cell (RBC) morphologies (biconcave, intermediate biconcave, intermediate polyhedrocyte, and polyhedrocyte) in the thrombi with scanning electron microscopy (n = 5) was used to determine degree of thrombus deposition/contraction. Very few biconcave RBCs (1.2 ± 0.6%) were in the thrombi, and greater amounts of intermediate biconcave RBCs (25.8 ± 6.7%) were located in the descending thoracic portion of the dissection while more polyhedrocytes (14.6 ± 5.1%) and fibrin (42.3 ± 4.5%; P < .05) were found in the distal suprarenal aorta. Thrombus deposition likely plays some role in patient outcomes, and this multimodality technique can help investigate thrombus deposition and characteristics in experimental animal models and human tissue samples.