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Objective: With the growing incidence of peripheral arterial disease (PAD) and the historic under-representation of female patients in cardiovascular trials, a comprehensive evaluation of sex-based variances in PAD presentation and treatment outcomes is needed. This study aims to evaluate sex-based differences in the vessel wall characteristics of patients who underwent amputation owing to critical limb-threatening ischemia to optimize personalized treatment planning and aid in the selection of endovascular devices for PAD patients. Methods: A total of 35 lower limbs were collected from 34 patients with end-stage PAD undergoing major amputation. We selected, harvested, and cross-sectioned at 3- to 4-mm intervals 163 diseased below-the-knee arterial segments resulting in 1260 arterial rings. Histological analyses were conducted on each individual ring and later summarized by arterial segment. Results: Male and female patients were remarkably similar across multiple plaque characteristics, including degree of stenosis, calcification severity and localization, and atherosclerotic patterns. A significant sex-based difference was noted in the presence of luminal thrombus, which was more prevalent in females (38.7% vs 25.0%; P = .016). Histopathological differences were noted between popliteal and tibial lesions, with popliteal segments demonstrating increased chronic total occlusion presence and atherosclerosis, whereas severe calcification occurred more often in tibial segments. A sex-based evaluation of the popliteal segments showed increased calcification (60.71% vs 28.0%; P = .003) and atherosclerosis (96.4% vs 73.0%; P = .028) in males compared with females. Conclusions: Differences in the degree of calcification, incidence of atherosclerosis, and presence of luminal thrombus may pose important clinical implications for antiplatelet and anticoagulation regimen choice and guide treatment options. Further studies are warranted to evaluate the impact of these differences on outcomes of endovascular procedures.

Introduction: Percutaneous deep venous arterialisation (DVA) is emerging as a promising alternative for limb salvage in chronic limb threatening ischaemia (CLTI) patients without any reasonable anatomical option for conventional revascularisation techniques. However, its mechanism of action remains incompletely understood. This report aimed to find some of the histological alterations occurring in the limb following DVA. Report: This short report presents the case of a 53 year old female who underwent DVA for Rutherford 5 CLTI. Although the intervention was successful and showed evidence of improved blood flow to the foot, the post-operative course was notable due to worsening infection leading to a below knee amputation four weeks later. The blood vessels were harvested for histological analysis, which found features of venous arterialisation such as smooth muscle cell proliferation and neointimal hyperplasia, even in the paired posterior tibial vein that did not undergo DVA. Discussion: This case demonstrated unexpected histological changes occurring in the paired posterior tibial vein that did not undergo DVA. This warrants further investigations to fully understand the mechanisms at play in DVA and to explore the role of the paired vein in sustaining arterialised flow to the foot.

With the growing prevalence and mortality of peripheral arterial disease, preoperative assessment, risk stratification, and determining the correct indication for endovascular and open surgical procedures are essential for therapeutic decision-making. The effectiveness of interventional procedures is significantly influenced by the plaque composition and calcification pattern. Therefore, the identification of patients for whom endovascular treatment is the most appropriate therapeutic solution often remains a challenge. The most commonly used imaging techniques have their own limitations and do not provide findings detailed enough for specific, personalized treatment planning. Using state-of-the-art noninvasive and invasive imaging modalities, it is now possible to obtain a view, not only of the complex vascular anatomy and plaque burden of the lower extremity arterial system, but also of complex plaque structures and various pathologic calcium distribution patterns. In the future, as these latest advancements in diagnostic methods become more widespread, we will be able to obtain more accurate views of the plaque structure and anatomic complexity to guide optimal treatment planning and device selection. We reviewed the implications of the most recent invasive and noninvasive lower extremity imaging techniques and future directions.

Objective: We evaluated how contemporary data on infrapopliteal vessel preparation have been reported to identify knowledge gaps and opportunities for future research. Methods: A literature search was performed on Web of Science, PubMed, and Google Scholar to identify clinical research studies reporting on the outcomes of vessel preparation in below-the-knee lesions between 2006 and 2021. Studies were excluded if they were case reports or case series with a sample size of

Summary: Background: Dracunculiasis (also known as Guinea worm disease), caused by the Dracunculus medinensis nematode, is progressing towards eradication, with a reduction in cases from 3·5 million cases in the mid-1980s to only 54 human cases at the end of 2019. Most cases now occur in Chad. On April 19, 2019, a 19-year-old woman presented with D medinensis in an area within the Salamat region of Chad, where the disease had not been previously reported. We aimed to investigate the connection between this case and others detected locally and elsewhere in Chad using a combination of epidemiological and genetic approaches. Methods: In this cross-sectional field study, we conducted household case searches and informal group interviews in the Bogam, Liwi, and Tarh villages in Chad. All community members including children were eligible for participation in the outbreak investigation. Adult female D medinensis associated with this outbreak were collected for genetic analysis (18 from humans and two from dogs). Four mitochondrial genes and 22 nuclear microsatellite markers were used to assess relatedness of worms associated with the outbreak in comparison with other worms from elsewhere in Chad. Findings: Between April 12 and Sept 6, 2019, we identified 22 human cases and two canine cases of dracunculiasis associated with 15 households. Six (40%) of the 15 affected households had multiple human or canine cases within the household. Most cases of dracunculiasis in people were from three villages in Salamat (21 [95%] of 22 cases), but one case was detected nearly 400 km away in Sarh city (outside the Salamat region). All people with dracunculiasis reported a history of consuming fish and unfiltered water. Worms associated with this outbreak were genetically similar and shared the same maternal lineage. Interpretation: Molecular epidemiological results suggest a point-source outbreak that originated from a single female D medinensis, rather than newly identified sustained local transmission. The failure of the surveillance system to detect the suspected canine infection in 2018 highlights the challenge of canine D medinensis detection, particularly in areas under passive surveillance. Human movement can also contribute to dracunculiasis spread over long distances. Funding: The Carter Center.

Background: The human gut microbiota has emerged as a key factor in the development of obesity. Certain probiotic strains have shown anti-obesity effects. The objective of this study was to investigate whether Bifidobacterium longum APC1472 has anti-obesity effects in high-fat diet (HFD)-induced obese mice and whether B. longum APC1472 supplementation reduces body-mass index (BMI) in healthy overweight/obese individuals as the primary outcome. B. longum APC1472 effects on waist-to-hip ratio (W/H ratio) and on obesity-associated plasma biomarkers were analysed as secondary outcomes. Methods: B. longum APC1472 was administered to HFD-fed C57BL/6 mice in drinking water for 16 weeks. In the human intervention trial, participants received B. longum APC1472 or placebo supplementation for 12 weeks, during which primary and secondary outcomes were measured at the beginning and end of the intervention. Findings: B. longum APC1472 supplementation was associated with decreased bodyweight, fat depots accumulation and increased glucose tolerance in HFD-fed mice. While, in healthy overweight/obese adults, the supplementation of B. longum APC1472 strain did not change primary outcomes of BMI (0.03, 95% CI [-0.4, 0.3]) or W/H ratio (0.003, 95% CI [-0.01, 0.01]), a positive effect on the secondary outcome of fasting blood glucose levels was found (-0.299, 95% CI [-0.44, -0.09]). Interpretation: This study shows a positive translational effect of B. longum APC1472 on fasting blood glucose from a preclinical mouse model of obesity to a human intervention study in otherwise healthy overweight and obese individuals. This highlights the promising potential of B. longum APC1472 to be developed as a valuable supplement in reducing specific markers of obesity. Funding: This research was funded in part by Science Foundation Ireland in the form of a Research Centre grant (SFI/12/RC/2273) to APC Microbiome Ireland and by a research grant from Cremo S.A.

Nutrition is a crucial component for maintenance of brain function and mental health. Accumulating evidence suggests that certain molecular compounds derived from diet can exert neuroprotective effects against chronic stress, and moreover improve important neuronal processes vulnerable to the stress response, such as plasticity and neurogenesis. Phospholipids are naturally occurring amphipathic molecules with promising potential to promote brain health. However, it is unclear whether phospholipids are able to modulate neuronal function directly under a stress-related context. In this study, we investigate the neuroprotective effects of phosphatidylcholine (PC), lysophosphatidylcholine (LPC), phosphatidylserine (PS), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylglycerol (PG), phosphatidic acid (PA), sphingomyelin (SM) and cardiolipin (CL) against corticosterone (CORT)-induced cytotoxicity in primary cultured rat cortical neurons. In addition, we examine their capacity to modulate proliferation and differentiation of hippocampal neural progenitor cells (NPCs).We show that PS, PG and PE can reverse CORT-induced cytotoxicity and neuronal depletion in cortical cells. On the other hand, phospholipid exposure was unable to prevent the decrease of Bdnf expression produced by CORT. Interestingly, PS was able to increase hippocampal NPCs neurosphere size, and PE elicited a significant increase in astrocytic differentiation in hippocampal NPCs. Together, these results indicate that specific phospholipids protect cortical cells against CORT-induced cytotoxicity and improve proliferation and astrocytic differentiation in hippocampal NPCs, suggesting potential implications on neurodevelopmental and neuroprotective pathways relevant for stress-related disorders.

Several non-native trematodes hosted by the invasive Eurasian faucet snail, Bithynia tentaculata, have been causing die-offs of waterfowl in the Midwestern United States and Canada for several decades. Because of the potential implications of these die-offs on waterfowl in non-native settings, it is necessary to better understand the trematodes that cause the die-offs. Here, we studied the spatio-temporal dynamics of two trematodes, Cyathocotyle bushiensis and Sphaeridiotrema spp., known to infect waterfowl in northern Minnesota, USA, via their intermediate host, the faucet snail (Bithynia tentaculata). We studied prevalence (% of snails infected within a sample) and intensity (mean number of parasites per infected snail within a sample) of faucet snail infection with these two trematodes in small lakes, large lakes, ponds, and rivers in northern Minnesota in the spring, summer, and fall of 2011–2013. We tested whether parasite prevalence and infection intensity could be explained spatially (as a function of the abundance of faucet snails, average snail size, water depth, and proximity to known waterfowl groups) and temporally (across years and seasons) using generalized estimating equation models. The spatial and temporal patterns we observed varied within and among waterbodies. For both parasite species, parasite prevalence and intensity of infection were consistently higher in samples with larger snails and in deeper portions of the waterbodies. In Lake Winnibigoshish, prevalence was lower farther from the large waterfowl groups we observed, but the abundance of snails in a sample had no effect on prevalence or intensity of infection. Our findings help improve understanding of this multi-species system, but also illustrate the complexity of modeling the spatial and temporal dynamics of infections in waterbodies that are so variable in size, shape, waterfowl use, and function. Keywords: Bithynia tentaculata, Cyathocotyle bushiensis, Faucet snail, Sphaeridiotrema spp., Trematodiasis, Waterfowl die-offs

LncRNAs and miRNAs, being the master regulators of gene expression, are crucial functional mediators in cancer. Our study unveils the critical regulatory role of the metastatic long non-coding RNA LINC00273 as the master regulator of oncogenes involved in cancer metastasis, stemness, and chemoresistance via its miRNA sponging mechanism. M2 (a salt of bis-Schiff base) mediated G quadruplex (G4) stabilization at the LINC00273 gene promoter remarkably inhibits LINC00273 transcription. Therefore, low-level LINC00273 transcripts are unable to efficiently sponge the miRNAs, which subsequently become available to bind and downregulate their target oncogenes. We have observed significantly different global transcriptomic scenarios in LINC00273 upregulated and downregulated circumstances in MDA-MB-231 triple-negative breast cancer model. Additionally, we have found the G4 sequence in the LINC00273 RNA to play a critical role in miRNA sequestration. miRNAs (miR-6789-5p, miR200b, miR-125b-5p, miR-4268, miR3978) have base pairing complementarity within the G4 region of LINC00273 RNA and the 3'-UTR (untranslated region) of MAPK12, TGF-β1, and SIX-1 transcripts. We have reported TGF-β1, SIX-1, and MAPK12 to be the direct downstream targets of LINC00273. The correlation between abnormal expression of lncRNA LINC00273 and TNBC aggressiveness strongly evidenced in our study shall accelerate the development of lncRNA-based anti-metastatic therapeutics., Competing Interests: Declaration of competing interest The authors declared no sign of conflict., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: Challenges from administrative support, scanners' heterogeneity, patient size variation, and protocol mapping hinder CT protocol and dose management. We present a holistic approach to overcome these challenges., Methods: A dose tracking software was selected with two key requirements: intelligent protocol mapping and customizable dose threshold settings according to the patient size. A multifaceted workflow was carefully implemented. It included patient size-dependent dose thresholds for e-mail alerts, a base protocol archive on a website with a unified format using an in-house developed reformat software upon protocol export, prompt dose alert follow-up, and well-controlled protocol changes. The thresholds were iteratively updated following protocol changes or review of dose statistics. The program outcome was evaluated using 11 protocols from January 2020 to May 2023 (N = 148,678) in comparison to ACR's achievable dose (AD) and dose reference levels (DRLs)., Results: The 75th percentile dose data were lower than the ACR's DRL on average, ranging from -4.9% to -36%. The median doses were in a range of -23% to 19% on average in comparison with the ACR's AD. The median value from pulmonary embolism scans initially showed 36% higher than the AD but was gradually reduced to nearly 3% lower than the AD. The percentage of unjustified alerted cases decreased from 80% in first half year of 2020 to 17% in the first 5 months of 2023., Conclusions: The results showed that our holistic approach to protocol and dose management has been effective. The impact to practice has been prompt and sustainable., (Copyright © 2024 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Reactive oxygen species (ROS) plays important role to maintain homeostasis in living bodies. Here we have studied interaction of ROS generated from hydrogen peroxide (H 2 O 2 ) with a well-known spectroscopic probe Rose Bengal (RB) encapsulated in nanoscopic sodium dodecyl sulphate (SDS) micelles in aqueous medium and entrapped in microscopic nylon 66 solid matrix generated using electrospinning technique. A detailed spectroscopic characterization of ROS with SDS encapsulated RB (RB-SDS) shows efficient interaction compared to that in bulk medium. The time resolved analysis on the probe based on femtosecond resolved 2D-spectrum time images collected from streak camera reveal the simultaneous existence of an ultrafast electron (∼6 ps) and a hole transfer mechanism (∼93 ps) resulting from generation of hydroxyl radicals through photobleaching of the probe in presence of H 2 O 2 . Based on the spectroscopic and time resolved studies of RB in bulk and in restricted (SDS) medium, we have further translated it for the development of an in-field prototype device which utilizes RB as a ROS sensor impregnated in a nylon thin film. The microscopic nylon solid matrix characterized by scanning electron microscope (SEM) shows porous structure for holding sample containing ROS. Our study quantitatively measures the amount of ROS by using RB embedded microfiber membrane. Thus, our developed prototype device based on RB embedded on the nylon matrix would be beneficial for the potential use in quantification of ROS in extracellular fluids and food materials., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The treatment of chronic myeloid leukemia relies on orally available tyrosine kinase inhibitors targeting the BCR::ABL1 oncoprotein. Bosutinib is a second generation adenosine triphosphate-competitive inhibitor approved for use in frontline adult chronic phase-chronic myeloid leukemia and all phases-chronic myeloid leukemia in the second line setting or beyond. Its efficacy was demonstrated in several pivotal clinical trials at 400mg once daily in the first line context and at 500mg once daily beyond first line. Bosutinib-related adverse events frequently occur early after treatment initiation and include gastro-intestinal symptoms and cytolytic hepatitis. These drug-related adverse events must be properly managed in order to preserve safety, efficacy and treatment acceptability. The French chronic myeloid leukemia study group gathered a panel of experts in hematology, pharmacology and hepatology in order to elaborate practical recommendations on the management of bosutinib treatment. These recommendations aim at optimizing the short and long-term tolerance and benefit/risk balance of bosutinib, mainly focusing at gastro-intestinal and liver toxicities., (Copyright © 2023 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Even in the era of smart technologies and IoT enabled devices, tea testing technique continues to be a person specific subjective task. In this study, we have employed optical spectroscopy-based detection technique for the quantitative validation of tea quality. In this regard, we have employed the external quantum yield of quercetin at 450 nm (λ ex  = 360 nm), which is an enzymatic product generated by the activity of β-glucosidase on rutin, a naturally occurring metabolite responsible for tea-flavour (quality). We have found that a specific point in a graph representing Optical Density and external Quantum Yield as independent and dependent variables respectively of an aqueous tea extract objectively indicates a specific variety of the tea. A variety of tea samples from various geographical origin have been analysed with the developed technique and found to be useful for the tea quality assessment. The principal component analysis distinctly showed the tea samples originated from Nepal and Darjeeling having similar external quantum yield, while the tea samples from Assam region had a lower external quantum yield. Furthermore, we have employed experimental and computational biology techniques for the detection of adulteration and health benefit of the tea extracts. In order to assure the portability/field use, we have also developed a prototype which confirms the results obtained in the laboratory. We are of the opinion that the simple user interface and almost zero maintenance cost of the device will make it useful and attractive with minimally trained manpower at low resource setting., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Several fusion genes such as BCR::ABL1, FIP1L1::PDGFRA, and PML::RARA are now efficiently targeted by specific therapies in patients with leukemia. Although these therapies have significantly improved patient outcomes, leukemia relapse and progression remain clinical concerns. Most myeloid next-generation sequencing (NGS) panels do not detect or quantify these fusions. It therefore remains difficult to decipher the clonal architecture and dynamics of myeloid malignancy patients, although these factors can affect clinical decisions and provide pathophysiologic insights. An asymmetric capture sequencing strategy (aCAP-Seq) and a bioinformatics algorithm (HmnFusion) were developed to detect and quantify MBCR::ABL1, μBCR::ABL1, PML::RARA, and FIP1L1::PDGFRA fusion genes in an NGS panel targeting 41 genes. One-hundred nineteen DNA samples derived from 106 patients were analyzed by conventional methods at diagnosis or on follow-up and were sequenced with this NGS myeloid panel. The specificity and sensitivity of fusion detection by aCAP-Seq were 100% and 98.1%, respectively, with a limit of detection estimated at 0.1%. Fusion quantifications were linear from 0.1% to 50%. Breakpoint locations and sequences identified by NGS were concordant with results obtained by Sanger sequencing. Finally, this new sensitive and cost-efficient NGS method allowed integrated analysis of resistant chronic myeloid leukemia patients and thus will be of interest to elucidate the mutational landscape and clonal architecture of myeloid malignancies driven by these fusion genes at diagnosis, relapse, or progression., (Copyright © 2022 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background This paper presents an assessment of the current emergency response to homeless people who use substances in Montreal, a major North American city. This project addresses the rising concern about homelessness in high-income countries. Several studies have shown that homeless people frequently use emergency services (i.e., police, paramedical, and hospital), especially in the context of substance use. Yet, the key actors' perspectives are poorly documented. Method Our team conducted a needs analysis using a deliberative democratic evaluation. Data collection strategies included an intersectoral World Café (n = 34, including police, specialized professionals, community stakeholders, political representatives, researchers, and people who have been homeless) and individual interviews with health professionals (n = 5) and homeless people (n = 8). We performed a thematic content analysis based on a conceptual framework of access to health care and of collaboration. Findings This study provided key information on the role of emergency services and the needs of key actors, in terms of the dimensions of access to health care (approachability, acceptability, availability, and appropriateness) and continuity. Our main results show that, according to the participants, the emergency response is relevant when homeless people are a danger to themselves or to others, and during episodes of acute physical and psychological care. However, emergency service providers still stigmatize homelessness and substance use, which negatively affects intervention quality. Finally, our main results highlight the interdependence between the emergency services and health, social, and community services. Conclusion The emergency response is necessary and appropriate in some situations. It remains important to intervene upstream and to improve the attitudes and practices of emergency service providers. Finally, it is necessary to adapt services to the needs of homeless substance users and improve service continuity, for example, by adopting a population-based approach., (Crown Copyright © 2020. Published by Elsevier B.V. All rights reserved.)

The poultry red mite, Dermanyssus gallinae, is the most significant pest of egg laying hens in many parts of the world. Control of D. gallinae could be greatly improved with advanced Integrated Pest Management (IPM) for D. gallinae in laying hen facilities. The development of a model forecasting the pests' population dynamics in laying hen facilities without and post-treatment will contribute to this advanced IPM and could consequently improve implementation of IPM by farmers. The current work describes the development and demonstration of a model which can follow and forecast the population dynamics of D. gallinae in laying hen facilities given the variation of the population growth of D. gallinae within and between flocks. This high variation could partly be explained by house temperature, flock age, treatment, and hen house. The total population growth variation within and between flocks, however, was in part explained by temporal variation. For a substantial part this variation was unexplained. A dynamic adaptive model (DAP) was consequently developed, as models of this type are able to handle such temporal variations. The developed DAP model can forecast the population dynamics of D. gallinae, requiring only current flock population monitoring data, temperature data and information of the dates of any D. gallinae treatment. Importantly, the DAP model forecasted treatment effects, while compensating for location and time specific interactions, handling the variability of these parameters. The characteristics of this DAP model, and its compatibility with different mite monitoring methods, represent progression from existing approaches for forecasting D. gallinae that could contribute to advancing improved Integrated Pest Management (IPM) for D. gallinae in laying hen facilities., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Among Gamasina (Acari: Mesostigmata) mites, some dermanyssoid species are known to cause gamasoidosis, a human dermatitis characterized by papulosquamous eruptions and urticarian lesions. We describe a case of mite infestation which occurred in public conference halls in Ferrara (Italy), affecting four people who attended the place and showed signs of gamasoidosis. The mites were collected and characterized using scanning electron microscopy, light microscopy and mitochondrial DNA sequencing (Cytochrome c oxidase subunit I partial CDS). Based on morphological and molecular data, the species responsible for the infestation was identified as the special lineage L1 of the poultry red mite, Dermanyssus gallinae (De Geer) (Acarina: Dermanissydae), a cryptic species known to be associated with pigeons. Rock doves, Columba livia Gmelin (Columbiformes: Columbidae) were roosting on the top of the public building, thus the mites probably gained access to the halls through small window openings. The present case report is the first one providing morpho-molecular identification of a D. gallinae cryptic species responsible of gamasoidosis in Italy., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Q methodology consists of a philosophical framework and procedures to identify subjective viewpoints that may not be well understood, but its use in nursing is still quite limited. We describe how Q methodology can be used in quality improvement projects to better understand local viewpoints that act as facilitators or barriers to the implementation of evidence-based practice. We describe the use of Q methodology to identify nurses' attitudes about the provision of skin-to-skin care after cesarean birth., (Copyright © 2017 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses. Published by Elsevier Inc. All rights reserved.)

Individuals with mental illnesses who experience homelessness have frequent interactions with the criminal justice system. Correctly measuring this involvement is essential to develop and evaluate the efficacy of intervention programs. Criminal justice involvement is typically assessed through administrative records or self-reported accounts. The aims of this study are to: 1) assess agreement between self-report and administrative data related to court appearances, and 2) identify individual characteristics that affect discrepancies between sources. Participants were 468 homeless persons with mental illness from the Montreal site of the At Home/Chez Soi randomized controlled trial, in Canada. Self-reported data was collected through an interviewer-administered questionnaire. Administrative data was collected through provincial and municipal court databases. Overall, agreement was good. Discrepancies were more common among those with a diagnosis of mood disorder with psychotic features, and those with a criminal history. Increased age and interviewer's perception of sincerity and interest increased likelihood of concordance. Generally, high agreement between self-report and administrative data suggests that either source can provide reliable information. Further work to understand predictors of discrepancies could further enhance the quality of data collected through these different sources., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objectives: This study examines whether baseline profiles of criminal justice involvement are independently associated with 24-month trajectories of arrests in a sample of homeless adults living with mental illness., Methods: Interviews with justice-involved participants from the At Home/Chez soi project, a multisite trial of Housing First in Canada, yielded information related to arrests, as well as demographic, clinical, and contextual predictors of criminal justice system involvement. All potential predictors were entered into logistic and negative binomial regression models to assess their effect on re-arrest., Results: Of the 584 individuals involved with the criminal justice system at baseline, and for whom follow-up data was obtained, 347 (59%) were re-arrested within two years. Of those, 283 (82%) had an episodic pattern of re-arrest and 64 (18%) had a continuous trajectory of re-arrest. Results indicate that participants involved with the legal system for minor (mostly theft and public order) offenses at baseline were most likely to be repeatedly arrested. Gender, Aboriginal status, and recent victimization were also independently associated with re-arrest., Conclusions: These findings have implications for the delivery of police and clinical services alike, as well as for policies that aim to divert vulnerable individuals who commit minor crimes from a long-term trajectory of justice involvement., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objectives: This study aims to examine the rates of self-reported contacts with the criminal justice system among homeless adults with mental illness, to identify the characteristics of participants who have had contacts with the criminal justice system, to report the dimensional structure of criminal justice system involvement in this sample, and to identify typologies of justice-involved participants., Methods: Self-report data on criminal justice system involvement of 2221 adults participating in a Canadian Housing First trial were analyzed using multiple correspondence and cluster analysis., Results: Almost half of the participants had at least one contact with the criminal justice system in the 6months prior to study enrollment. Factors associated with justice involvement included age, gender, ethnic background, diagnosis, substance misuse, impulse control, compliance, victimization, service use, and duration of homelessness. A typology of criminal justice involvement was developed. Seven criminal justice system involvement profiles emerged; substance use and impulse control distinguished the clusters, whereas demographic and contextual variables did not., Conclusions: The large number of profiles indicates the need for a diverse and flexible range of interventions that could be integrated within or in addition to current support of housing services, including integrated substance use and mental health interventions, risk management strategies, and trauma-oriented services., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

This work examines cocrystal solubility in biorelevant media (FeSSIF, fed-state simulated intestinal fluid), and develops a theoretical framework that allows for the simple and quantitative prediction of cocrystal solubilization from drug solubilization. The solubilities of four hydrophobic drugs and seven cocrystals containing these drugs were measured in FeSSIF and in acetate buffer at pH 5.00. In all cases, the cocrystal solubility (Scocrystal ) was higher than the drug solubility (Sdrug ) in both buffer and FeSSIF; however, the solubilization ratio of drug, SRdrug = (SFeSSIF /Sbuffer )drug , was not the same as the solubilization ratio of cocrystal, SRcocrystal = (SFeSSIF /Sbuffer )cocrystal , meaning drug and cocrystal were not solubilized to the same extent in FeSSIF. This highlights the potential risk of anticipating cocrystal behavior in biorelevant media based on solubility studies in water. Predictions of SRcocrystal from simple equations based only on SRdrug were in excellent agreement with measured values. For 1:1 cocrystals, the cocrystal solubilization ratio (SR) can be obtained from the square root of the drug SR. For 2:1 cocrystals, SRcocrystal is found from (SRdrug )(2/3) . The findings in FeSSIF can be generalized to describe cocrystal behavior in other systems involving preferential solubilization of a drug such as surfactants, lipids, and other drug solubilizing media., (© 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.)

Background: Very few data exist on the long-term follow-up of patients with intermediate nonobstructive saphenous vein graft (SVG) lesions. The purpose of this study was to evaluate the 5-year clinical outcomes of the patients enrolled in the Moderate Vein Graft Lesion Stenting With the Taxus Stent and Intravascular Ultrasound (VELETI) and the factors associated with SVG disease progression and outcomes., Methods: Patients with ≥ 1 intermediate SVG lesion (30%-60% diameter stenosis) were randomized to either stenting the SVG lesion with a paclitaxel-eluting stent (PES group, n = 30) or to medical treatment alone (MT group, n = 27). All patients were followed yearly up to 5 years., Results: Major adverse cardiac events (MACEs) (cardiac death, myocardial infarction [MI], revascularization) related to the target SVG lesion tended to be lower in the PES group (17% vs 33%; P = 0.146) due to a lower lesion revascularization rate (13% vs 33%; P = 0.072), with no difference in cardiac death or MI between groups. MACEs related to the target SVG and global MACEs were similar between groups (P > 0.20 for both). A higher cholesterol level at baseline was the only independent predictive factor of MACEs related to the target SVG (P = 0.016)., Conclusions: Over a 5-year period, one third of intermediate lesions in old SVGs progressed, leading to a cardiac event. Stenting these lesions with PESs tended to improve clinical outcomes by reducing lesion progression but not SVG failure. Higher cholesterol levels were associated with SVG disease progression and clinical events. This pilot study provides the basis for a larger trial to determine the efficacy of intermediate SVG lesion plaque sealing., (Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Objectives: To study the causes of and to develop a risk score for failure of transradial approach (TRA) for percutaneous coronary intervention (PCI)., Background: TRA-PCI failure has been reported in 5% to 10% of cases., Methods: TRA-PCI failure was categorized as primary (clinical reasons) or crossover failure. Multivariate analysis was performed to determine independent predictors of TRA-PCI failure, and an integer risk score was developed., Results: From January to June 2010, TRA-PCI was attempted in 1,609 (97.3%) consecutive patients, whereas 45 (2.7%) had primary TRA-PCI failure. Crossover TRA-PCI failure occurred in 30 (1.8%) patients. Causes of primary TRA-PCI failure included chronic radial artery occlusion (11%), previous coronary artery bypass graft (27%), and cardiogenic shock (20%). Causes for crossover TRA-PCI failure included: inadequate puncture in 17 patients (57%); radial artery spasm in 5 (17%); radial loop in 4 (13%); subclavian tortuosity in 2 (7%); and inadequate guide catheter support in 2 (7%) patients. Female sex (odds ratio [OR]: 3.2; 95% confidence interval [CI]: 1.95 to 5.26, p < 0.0001), previous coronary artery bypass graft (OR: 6.1; 95% CI: 3.63 to 10.05, p < 0.0001), and cardiogenic shock (OR: 11.2; 95% CI: 2.78 to 41.2, p = 0.0011) were independent predictors of TRA-PCI failure. Risk score values from 0 to 7 predicted a TRA-PCI failure rate from 2% to 80%., Conclusions: In a high-volume radial center, 2.7% of patients undergoing PCI are excluded from initial TRA on clinical grounds, whereas crossover to femoral approach is required in only 1.8% of the cases. A new simple clinical risk score is developed to predict TRA-PCI failure., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Uncontrolled hypertension is associated with an increased risk of end-stage renal disease (ESRD). Intensified blood pressure control may slow progression of chronic kidney disease; however, the impact of antihypertensive agent adherence on the prevention of ESRD has never been evaluated. Here we assessed the impact of antihypertensive agent adherence on the risk of ESRD in 185,476 patients in the RAMQ databases age 45 to 85 and newly diagnosed/treated for hypertension between 1999 and 2007. A case cohort study design was used to assess the risk of and multivariate Cox proportional models were used to estimate the adjusted hazard ratio of ESRD. Adherence level was reported as a medication possession ratio. Mean patient age was 63 years, 42.2% male, 14.0% diabetic, 30.3% dyslipidemic, and mean follow-up was 5.1 years. A high adherence level of 80% or more to antihypertensive agent(s) compared to a lower one was related to a risk reduction of ESRD (hazard ratio 0.67; 95% confidence intervals 0.54-0.83). Sensitivity analysis revealed that the effect is mainly in those without chronic kidney disease. Risk factors for ESRD were male, diabetes, peripheral artery disease, chronic heart failure, gout, previous chronic kidney disease, and use of more than one agent. Thus, our study suggests that a better adherence to antihypertensive agents is related to a risk reduction of ESRD and this adherence needs to be improved to optimize benefits.

Purpose: The onset of a BCR-ABLT315I mutation during the course of chronic myelogenous leukemia (CML) on tyrosine kinase inhibitors (TKIs) usually results in poor survival, and therapeutic options remain few in the absence of any allogeneic donor., Patients and Methods: We have investigated the affect of subcutaneous omacetaxine (OMA, or homo-harringtonine) cycles on unmutated and T315I-mutated BCR-ABL transcripts in a series of 8 TKI-resistant chronic-phase CML patients and we have addressed the question of whether the administration of OMA could resensitize patients to TKIs. Patients were regularly monitored for total disease burden and for BCR-ABLT315I transcripts using a new quantitative sensitive technique (sensitivity threshold, 0.05%), for up to 27 cycles of OMA., Results: Overall, patients demonstrated hematologic, cytogenetic, or molecular improvement. An initial rapid decline and a sustained disappearance of T315I-mutated transcripts were observed in 50% of patients, after a median of 10.5 cycles (range, 3-27 cycles) of OMA. As the unmutated leukemic burden reduction was modest, 2 patients were submitted to nilotinib after 9 months of sustained BCR-ABLT315I transcripts negativity on OMA and mutated transcripts remained undetectable after a median follow-up of 12 months on nilotinib challenge., Conclusion: We suggest that OMA (ie, a non-targeted therapy) might provide a better disease control allowing the disappearance of the mutated clone probably elicited by the clone deselection after TKI release, and/or a preferential activity of OMA on the T315I-mutated cells through unknown mechanisms. These observations suggest that OMA could allow a safe TKI rechallenge in patients with resistant chronic-phase CML.

Background: Primary percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI) may be limited by thrombus embolization. Export aspiration catheter (EAC) is a thrombectomy device which may enhance angiographic results, but its impact on clinical outcomes is unclear. This trial objective was to assess the impact of EAC on angiographic and clinical outcomes in patients with STEMI., Methods: All STEMI patients undergoing primary or rescue PCI in a tertiary care center were included. Patients were divided in two groups according to the use of the EAC. Patients were followed up prospectively for death, reinfarction, revascularization, or stroke. Thrombolysis In Myocardial Infarction (TIMI) flow in the culprit vessel was assessed before and after PCI., Results: Included in the analysis were 535 patients. EAC was used in 165 patients before angioplasty (Group 1) and 370 patients underwent PCI without thrombus aspiration (Group 2). More patients in Group 1 had initial TIMI flow 0-1 compared to Group 2 (88% vs. 62%, P<.001). Proportion of patients with a final TIMI flow 3 was the same in both groups (89.1% vs. 87.6% for Groups 1 and 2, respectively; P=.67). An analysis restricted to patients with initial TIMI flow 0-1 yielded similar results. No difference in clinical outcomes was observed between the two groups (P=.70)., Conclusions: Selective use of the EAC based on the judgment of operators results in excellent angiographic and clinical results. Further clinical investigation is needed to definitely answer whether thromboaspiration needs to be performed in all STEMI patients undergoing primary PCI., (Crown Copyright © 2010. Published by Elsevier Inc. All rights reserved.)

An important attribute of cocrystals is that their properties can be tailored to meet required solubility and stability specifications. But before such practical uses can be realized, a better understanding of the factors that dictate co-crystal behavior is needed. This study attempts to explain the phase behavior of anhydrous/hydrated cocrystals when the coformer modulates both water activity and co-crystal solubility. Stability dependence on solution composition and water activity was studied for theophylline-citric acid (THP-CTA) anhydrous and hydrated cocrystals by both suspension and vapor equilibration methods. Eutectic points and associated water activities were measured by suspension equilibration methods to determine stability regions and phase diagrams. The critical water activity for the anhydrous-hydrate co-crystal was found to be 0.8. It is shown that (a) both water and coformer activities determine phase stability, and (b) excipients that alter water activity can profoundly affect the hydrate/anhydrous eutectic points and phase stability. Vapor phase stability studies demonstrate that cocrystals of highly water soluble coformers, such as citric acid, are predisposed to conversions due to moisture uptake and deliquescence of the coformer. The presence of such coformers as trace level impurities with co-crystal will alter hygroscopic behavior and stability.

Objectives: To assess the efficacy and safety of rosiglitazone on saphenous vein graft (SVG) atherosclerosis prevention and on modification of the global cardiometabolic risk profile., Methods and Results: This was a double-blind, randomized, placebo-controlled, multicenter trial which enrolled 193 post-CABG patients with type 2 diabetes. Atherosclerosis changes in one SVG were assessed with intravascular ultrasound at baseline and at 12 months. Serial cardiometabolic assessments were performed. At baseline, both groups had mean HbA(1C)<7%, LDL-cholesterol (LDL-C)<2.3 mmol/l, HDL-cholesterol (HDL-C)>1.0 mmol/l and blood pressure<130/75 mmHg. After 12 months, plaque volume in SVG had increased (median [interquartile range]) by 7.7 mm(3) (-17.2 to 37.9) in the placebo group and decreased by 0.3mm(3) (-19.1 to 22.3) in the rosiglitazone group (P=0.22). Compared to placebo, rosiglitazone treated patients had a higher (mean + or - SD) body weight (89 + or - 15 kg vs. 84 + or - 15 kg, P=0.02) at the end of the study, mostly related to an increment in subcutaneous adipose tissue. Rosiglitazone treated patients also displayed further improvements in glycemic control compared to placebo (HbA(1C): 6.4 + or - 0.7% vs. 7.0 + or - 0.9%, P<0.001) as well as in several cardiometabolic parameters such as lipids (HDL-C: 1.16 + or - 0.28 mmol/l vs. 1.06 + or - 0.23 mmol/l, P=0.003), inflammatory profile (C-reactive protein: 0.92 mg/l [0.51-1.56] vs. 1.37 mg/l [0.79-3.08], P=0.02), and adiponectin levels (11.1 microg/ml [8.19-17.9] vs. 4.65 microg/ml [3.27-7.15], P<0.001). There was no significant difference in the incidence of serious adverse cardiovascular events. However, more patients in the rosiglitazone group had peripheral oedema (33% vs. 18%, P=0.0019)., Conclusion: After a 12-month follow-up, we found no evidence for a statistically significant effect of rosiglitazone on SVG atherosclerosis whereas significant effects on glycemic control and on the cardiometabolic risk profile appeared to be modulated in part by changes in subcutaneous adiposity., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

We identified a novel breakpoint cluster region-ABL rearrangement in a chronic myeloid leukemia (CML) patient. The e14/a2 (b3/a2) type BCR-ABL mRNA incorporated a 42-nucleotide intronic insertion of ABL intron Ib between BCR exon e14 and ABL exon a2. As we hypothesized that the rearrangement between BCR and ABL genes occurred near the inserted sequence and because of the relative small size of BCR intron 14, we determined the BCR-ABL breakpoint at the genomic DNA level. Using a PCR-based method, this analysis revealed that i) BCR intron 14 brought a potential lariat branch point and the polypyrimidine tract, ii) the BCR-ABL breakpoint created a chimeric acceptor site, and iii) the inserted sequence of ABL intron Ib carried at its 3' end a well-conserved donor splice site. Therefore, the inserted sequence was flanked by canonical consensus splice sites and recognized as a pseudo-exon (as shown by splice site prediction and exon finder software). Moreover, the insertion did not disrupt the reading frame between BCR and ABL and did not produce a premature stop codon. Instead, this novel BCR-ABL chimeric transcript encoded a functional oncoprotein with an in-frame insertion of 15 new amino acids.

Background: In recent years, the concept of minimally invasive surgery has invaded the orthopaedic field and literature on the subject is spawning. Mini-incision surgery for total hip arthroplasty has been studied without a clear consensus on the efficacy, safety and advantage of that technique. To our knowledge, the efficacy and safety of mini-incisions in hip fracture surgery has not been studied in a randomised fashion., Methods: This study is a prospective clinically randomised trial whose primary objective was to demonstrate the safety and efficacy of a single posterior mini-incision approach compared to a standard posterior approach for endoprosthesis in acute femoral neck fractures. The mini-incision was defined as less than 8 cm. 25 patients in the mini-incision surgery (MIS) group and 31 patients in the standard incision group (STD) were available for analysis. The following validated disease-specific outcome instruments were used: the Lower Extremity Measurement (LEM) and the Time Up and Go (TUG). Secondary endpoints of pain, function, and quality of life were assessed by the components of the Harris Hip Score (HHS) and SF-36. Radiographic outcomes were also evaluated as well as the rates of all reported complications and adverse events during the 2 years follow-up., Results: There was no significant difference for operative time, blood losses, 72 h postoperative haemoglobin as well as the need for transfusion therapy between the two groups. Also, there was no difference between the groups for postoperative morphine use and pain evaluation with the Visual Analog Scale. The functional assessment using LEM and TUG did not demonstrate any statistically significant difference between mini- and standard incision. However, the HHS and the physical function component of the SF-36 were statistically better at 2 years in favour of the standard incision group., Conclusion: Based on the results of the present study, we cannot recommend the use of a minimally invasive approach over a standard approach in the implantation of a cemented endoprosthesis., (Crown Copyright (c) 2009. Published by Elsevier Ltd. All rights reserved.)

This study was conducted to explore the most effective vector control tool among indoor residual spraying (IRS), long lasting insecticidal nets (LLINs) and ecological vector management (EVM) as a part of the regional visceral leishmaniasis elimination initiative. Alpha-cypermethrin as IRS, PermaNet as LLINs and plastering the inner walls of houses with lime as EVM were the interventions. One baseline and three follow-up entomological surveys were carried out in all arms using CDC miniature light traps (LT) and mouth aspirators. Comparisons were made between intervention arms and control arms with pre-intervention and post-intervention vector densities. Light traps were found more efficient in the collection of Phlebotomus argentipes in comparison with aspiration. Vector densities were significantly low in both IRS arm (p=0.009 in LT and p<0.001 in aspirator collections) and LLIN arm (p=0.019 in LT and p=0.023 in aspirator collections) in comparison with control arm. However, in EVM arm, there was no significant difference in P. argentipes sand fly density in comparison with control arm (p=0.785) in LT collections in follow-up surveys. Hence, IRS was found most effective control measure to decrease vector density. LLINs were also found effective and can be considered as a promising alternative vector control tool in VL elimination initiative., (Copyright 2009 Elsevier B.V. All rights reserved.)