A Comparison of Palliative Care Delivery between Ethnically Chinese and Non-Chinese Canadians in the Last Year of Life.

BACKGROUND: Ethnically Chinese adults in Canada and the United States face multiple barriers in accessing equitable, culturally respectful care at the end-of-life. Palliative care (PC) is committed to supporting patients and families in achieving goal-concordant, high-quality serious illness care. Yet, current PC delivery may be culturally misaligned. Therefore, understanding ethnically Chinese patients' use of palliative care may uncover modifiable factors to sustained inequities at the end-of-life. OBJECTIVE: To compare the use and delivery of PC in the last year of life between ethnically Chinese and non-Chinese adults. DESIGN: Population-based cohort study. PARTICIPANTS: All Ontario adults who died between January 1st, 2012, and October 31st, 2022, in Ontario, Canada. EXPOSURES: Chinese ethnicity. MAIN MEASURES: Elements of physician-delivered PC, including model of care (generalist; specialist; mixed), timing and location of initiation, and type of palliative care physician at initial consultation. KEY RESULTS: The final study cohort included 527,700 non-Chinese (50.8% female, 77.9 ± 13.0 mean age, 13.0% rural residence) and 13,587 ethnically Chinese (50.8% female, 79.2 ± 13.6 mean age, 0.6% rural residence) adults. Chinese ethnicity was associated with higher likelihoods of using specialist (adjusted odds ratio [aOR] 1.53, 95%CI 1.46-1.60) and mixed (aOR 1.32, 95%CI 1.26-1.38) over generalist models of PC, compared to non-Chinese patients. Chinese ethnicity was also associated with a higher likelihood of PC initiation in the last 30 days of life (aOR 1.07, 95%CI 1.03-1.11), in the hospital setting (aOR 1.24, 95%CI 1.18-1.30), and by specialist PC physicians (aOR 1.33, 95%CI 1.28-1.38). CONCLUSIONS: Chinese ethnicity was associated with a higher likelihood of mixed and specialist models of PC delivery in the last year of life compared to adults who were non-Chinese. These observed differences may be due to later initiation of PC in hospital settings, and potential differences in unmeasured needs that suggest opportunities to initiate early, community-based PC to support ethnically Chinese patients with serious illness.

A Halogen-Bond-Driven Artificial Chloride-Selective Channel Constructed from 5-Iodoisophthalamide-based Molecules.

Despite considerable emphasis on advancing artificial ion channels, progress is constrained by the limited availability of small molecules with the necessary attributes of self-assembly and ion selectivity. In this study, a library of small molecules based on 5-haloisophthalamide and a non-halogenated isophthalamide were examined for their ion transport properties across the lipid bilayer membranes, and the finding demonstrates that the di-hexyl-substituted 5-iodoisophthalamide derivative exhibits the highest level of activity. Furthermore, it was established that the highest active compound facilitates the selective chloride transport that occurs via an antiport-mediated mechanism. The crystal structure of the compound unveils a distinctive self-assembly of molecules, forming a zig-zag channel pore that is well-suited for the permeation of anions. Planar bilayer conductance measurements proved the formation of chloride selective channels. A molecular dynamics simulation study, relying on the self-assembled component derived from the crystal structure, affirmed the paramount significance of intermolecular hydrogen bonding in the formation of supramolecular barrel-rosette structures that span the bilayer. Furthermore, it was demonstrated that the transport of chloride across the lipid bilayer membrane is facilitated by the synergistic effects of halogen bonding and hydrogen bonding within the channel.

Identifying research practices toward achieving health equity principles within the Cancer Prevention and Control Research Network.

PURPOSE: Although there is national recognition for health equity-oriented research, there is limited guidance for researchers to engage partnerships that promote health equity in cancer research. The Cancer Prevention and Control Research Network's (CPCRN) Health Equity Work Group developed a toolkit to guide researchers in equitable collaborations. METHODS: The CPCRN's Health Equity Work Group collectively outlined health and racial equity principles guiding research collaborations with partners that include communities, community-based organizations, implementing partners in the clinical setting including providers and health care organizations, and policy makers. Using a network-wide survey to crowdsource information around ongoing practices, we leveraged and integrated the network's experience and collaborations. RESULTS: Data from the survey formed the preliminary basis for the toolkit, with a focus on sharing fiscal resources with partners, training and capacity building, collaborative decision-making, community-driven research agenda setting, and sustainability. The final toolkit provides reflection considerations for researchers and collated exemplary resources, supported by the contemporary research. CONCLUSIONS: The toolkit provides a guide to researchers at all experience levels wanting to engage in equitable research collaborations. Future efforts are underway to evaluate whether and how researchers within and outside CPCRN are able to incorporate these principles in research collaborations.

Understanding the Role of Caseworker-Cultural Mediators in Addressing Healthcare Inequities for Patients with Limited-English Proficiency: a Qualitative Study.

BACKGROUND: Patients with limited-English proficiency (LEP) face multiple barriers to equitable healthcare. Interventions that go beyond interpretation, such as the use of bicultural-bilingual patient navigators, hold promise for addressing multi-level barriers. However, data about how to operationalize the tasks that are key to such interventions across diverse LEP communities are lacking. OBJECTIVE: Using our health system's bicultural-bilingual caseworker-cultural mediator (CCM) program serving Amharic-, Cambodian/Khmer-, Somali-, Spanish-, and Vietnamese-speaking patients, we sought to understand the key tasks that comprise the CCMs' role and how these tasks enable them to address barriers to healthcare for patients with LEP. DESIGN: Semi-structured interviews were conducted in 2019 with a purposive sample (n=23) of clinicians, CCMs, and patients with LEP or their family members from all language groups. PARTICIPANTS: Patients or family members receiving CCM services, CCMs, and clinicians who referred patients to the program. APPROACH: Content analysis consisting of a hybrid deductive-inductive qualitative approach. KEY RESULTS: Seven CCM tasks were identified: advocacy, care coordination, navigation, interpretation, education, mediation, and emotional support. Additionally, four key impacts emerged that described the ways in which these tasks enabled the CCMs to facilitate equitable care: bridging the patient, family, community, clinical team, and healthcare system; impacting knowledge of cultural issues and of the healthcare system; troubleshooting cultural barriers and problem solving; and enhancing relationship building. CONCLUSIONS: We identified several tasks and impacts that enabled CCMs to address multi-level barriers to care experienced by patients with LEP and their families across diverse cultural and linguistic groups. Findings suggest opportunities for the generalizability of programs such as ours for multiple LEP populations. Additionally, interventions having a greater scope than interpretation and including relationships with communities may be more successful in addressing barriers to equitable care at the individual, system, and community levels.

Multiple ocean parameter-based potential fishing zone (PFZ) location generation and validation in the Western Bay of Bengal.

A new conceptual framework based on satellite data, including chlorophyll (CHL), sea surface temperature (SST) fronts, relative winds, current vectors, Ekman transport, and eddies, has been developed to identify potential fishing zones (PFZ) in the Bay of Bengal (BoB). The framework aims to provide persistent forecasts, even under cloudy conditions, based on feature propagation. The validation of the PFZ was carried out using fish catch data collected by the Fishery Survey of India (FSI) between 2016 and 2018. Hooking rates (HR) from longlines and catch per unit effort (CPUE) from trawl nets were used to analyse the data points in hook rate categories (1.0-3.0 and > 3.0) and CPUE categories (50-100 kg and > 100 kg) and interpret them with the PFZ maps. The analysis showed that the high fish catch locations were consistent with persisting features in the BoB, such as high chlorophyll patches, SST fronts, and cyclonic eddies. The high fish catch locations based on hook rate and high CPUE were found to be collocated with the high chlorophyll persisting features and thermal gradients in the BoB. The regression analysis shows that availability of the food (CHL) had the strongest correlation with fish catch, followed by the comfort condition (fronts and eddies).

Supramolecular Barrel-Rosette Ion Channel Based on 3,5-Diaminobenzoic Acid for Cation-Anion Symport.

The structural tropology and functions of natural cation-anion symporting channels have been continuously investigated due to their crucial role in regulating various physiological functions. To understand the physiological functions of the natural symporter channels, it is vital to develop small-molecule-based biomimicking systems that can provide mechanistic insights into the ion-binding sites and the ion-translocation pathways. Herein, we report a series of bis((R)-(-)-mandelic acid)-linked 3,5-diaminobenzoic acid based self-assembled ion channels with distinctive ion transport ability. Ion transport experiment across the lipid bilayer membrane revealed that compound 1 b exhibits the highest transport activity among the series, and it has interesting selective co-transporting functions, i.e., facilitates K+ /ClO4 - symport. Electrophysiology experiments confirmed the formation of supramolecular ion channels with an average diameter of 6.2±1 Šand single channel conductance of 57.3±1.9 pS. Selectivity studies of channel 1 b in a bilayer lipid membrane demonstrated a permeability ratio of P C l - / P K + = 0 . 053 ± 0 . 02 ${{P}_{{Cl}^{-}}/{P}_{{K}^{+}}=0.053\pm 0.02}$ , P C l O 4 - / P C l - = 2 . 1 ± 0 . 5 ${{P}_{{ClO}_{4}^{-}}/{P}_{{Cl}^{-}}=2.1\pm 0.5}$ , and P K + / P N a + = 1 . 5 ± 1 , ${{P}_{{K}^{+}}/{P}_{{Na}^{+}}=1.5\pm 1,}$ indicating the higher selectivity of the channel towards KClO4 over KCl salt. A hexameric assembly of a trimeric rosette of 1 b was subjected to molecular dynamics simulations with different salts to understand the supramolecular channel formation and ion selectivity pattern.

Bis(cholyl)-based chloride channels with oxalamide and hydrazide selectivity filters.

We report the development of supramolecular bis(cholyl) ion channels using oxalamide and hydrazide as selectivity filters. The hydrazide system showed superior chloride transport activity to oxalamide via the formation of a barrel stave channel. The better chloride recognition within the hydrazide channel over the oxalalmide channel was confirmed from the theoretical calculations.

Characterizing uncertainty in goals-of-care discussions among black and white patients: a qualitative study.

BACKGROUND: Uncertainty has been associated with distress and poorer quality of life in patients with advanced cancer. Prior studies have focused on prognostic uncertainty; little is known about other types of uncertainty that patients and family members experience when discussing goals of care. Understanding the types of uncertainty expressed and differences between Black and White patients can inform the development of uncertainty management interventions. METHODS: This study sought to characterize the types of uncertainty expressed by Black and White patients and family members within the context of information needs during inpatient goals-of-care discussions. We performed a secondary analysis of transcripts from 62 recorded goals-of-care discussions that occurred between 2012 and 2014 at an urban, academic medical center in the United States. We applied an adapted taxonomy of uncertainty to data coded as describing information needs and used an inductive qualitative analysis method to analyze the discussions. We report the types of uncertainty expressed in these discussions. RESULTS: Fifty discussions included patient or family expressions of information needs. Of these, 40 discussions (n=16 Black and n=24 White) included statements of uncertainty. Black and White patients and families most frequently expressed uncertainty related to processes and structures of care (system-centered uncertainty) and to treatment (scientific uncertainty). Statements of prognostic uncertainty focused on quantitative information among Whites and on qualitative information and expectations for the future among Blacks. CONCLUSIONS: Black and White patients and families frequently expressed system-centered uncertainty, suggesting this may be an important target for intervention. Addressing other sources of uncertainty, such as prognostic uncertainty, may need more tailored approaches.

Anti-interleukin-13 and anti-interleukin-4 agents versus placebo, anti-interleukin-5 or anti-immunoglobulin-E agents, for people with asthma.

BACKGROUND: Targeting the immunoglobulin E pathway and the interleukin-5 pathway with specific monoclonal antibodies directed against the cytokines or their receptors is effective in patients with severe asthma. However, there are patients who have suboptimal responses to these biologics. Since interleukin-4 and interleukin-13, signalling through the interleukin-4 receptor, have multiple effects on the biology of asthma, therapies targeting interleukin-4 and -13 (both individually and combined) have been developed. OBJECTIVES: To assess the efficacy and safety of anti-interleukin-13 or anti-interleukin-4 agents, compared with placebo, anti-immunoglobulin E agents, or anti-interleukin-5 agents, for the treatment of children, adolescents, or adults with asthma. SEARCH METHODS: We identified studies from the Cochrane Airways Trials Register, which is maintained by the Information Specialist for the Group and through searches of the US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform. The search was carried out on the 16 October 2020. SELECTION CRITERIA: We included parallel-group randomised controlled trials that compared anti-interleukin-13 or -4 agents (or agents that target both interleukin-13 and interleukin-4) with placebo in adolescents and adults (aged 16 years or older) or children (younger than 16 years), with a diagnosis of asthma; participants could receive their usual short- or long-acting medications (e.g. inhaled corticosteroids (ICS), long-acting beta adrenoceptor agonists (LABA), long-acting muscarinic antagonists (LAMA), and/or leukotriene receptor antagonists) provided that they were not part of the randomised treatment. DATA COLLECTION AND ANALYSIS: We used standard methods expected by Cochrane. MAIN RESULTS: We identified and included 41 RCTs. Of these, 29 studies contributed data to the quantitative analyses, randomly assigning 10,604 people with asthma to receive an anti-interleukin-13 (intervention) or anti-interleukin-4 agent (intervention), or placebo (comparator). No relevant studies were identified where the comparator was an anti-immunoglobulin agent or an anti-interleukin-5 agent. Studies had a duration of between 2 and 52 (median 16) weeks. The mean age of participants across the included studies ranged from 22 to 55 years. Only five studies permitted enrolment of children and adolescents, accounting for less than 5% of the total participants contributing data to the present review. The majority of participants had moderate or severe uncontrolled asthma. Concomitant ICS use was permitted or required in the majority (21 of 29) of the included studies. The use of maintenance systemic corticosteroids was not permitted in 19 studies and was permitted or required in five studies (information not reported in five studies). Regarding the most commonly assessed anti-interleukin-13/-4 agents, four studies evaluated dupilumab (300 mg once every week (Q1W), 200 mg once every two weeks (Q2W), 300 mg Q2W, 200 mg once every four weeks (Q4W), 300 mg Q4W, each administered by subcutaneous (SC) injection); eight studies evaluated lebrikizumab (37.5 mg Q4W, 125 mg Q4W, 250 mg Q4W each administered by SC injection); and nine studies (3259 participants) evaluated tralokinumab (75 mg Q1W, 150 mg Q1W, 300 mg Q1W, 150 mg Q2W, 300 mg Q2W, 600 mg Q2W, 300 mg Q4W, each administered by SC injection; 1/5/10 mg/kg administered by intravenous (IV) injection); all anti-interleukin-13 or-4 agents were compared with placebo. The risk of bias was generally considered to be low or unclear (insufficient detail provided); nine studies were considered to be at high risk for attrition bias and three studies were considered to be at high risk for reporting bias. The following results relate to the primary outcomes. The rate of exacerbations requiring hospitalisation or emergency department (ED) visit was probably lower in participants receiving tralokinumab versus placebo (rate ratio 0.68, 95% CI 0.47 to 0.98; moderate-certainty evidence; data available for tralokinumab (anti-interleukin-13) only). In participants receiving an anti-interleukin-13/-4 agent, the mean improvement versus placebo in adjusted asthma quality of life questionnaire score was 0.18 units (95% CI 0.12 to 0.24; high-certainty evidence); however, this finding was deemed not to be a clinically relevant improvement. There was likely little or no difference between groups in the proportion of patients who reported all-cause serious adverse events (anti-interleukin-13/-4 agents versus placebo, OR 0.91, 95% CI 0.76 to 1.09; moderate-certainty evidence). In terms of secondary outcomes, there may be little or no difference between groups in the proportion of patients who experienced exacerbations requiring oral corticosteroids (anti-interleukin-13/-4 agents versus placebo, rate ratio 0.98, 95% CI 0.72 to 1.32; low-certainty evidence). Anti-interleukin-13/-4 agents probably improve asthma control based on asthma control questionnaire score (anti-interleukin-13/-4 agents versus placebo, mean difference -0.19; 95% CI -0.24 to -0.14); however, the magnitude of this result was deemed not to be a clinically relevant improvement. The proportion of patients experiencing any adverse event was greater in those receiving anti-interleukin-13/-4 agents compared with those receiving placebo (OR 1.16, 95% CI 1.04 to 1.30; high-certainty evidence); the most commonly reported adverse events in participants treated with anti-interleukin-13/-4 agents were upper respiratory tract infection, nasopharyngitis, headache and injection site reaction. The pooled results for the exploratory outcome, the rate of exacerbations requiring oral corticosteroids (OCS) or hospitalisation or emergency department visit, may be lower in participants receiving anti-interleukin-13/-4 agents versus placebo (rate ratio 0.71, 95% CI 0.65 to 0.77; low-certainty evidence). Results were generally consistent across subgroups for different classes of agent (anti-interleukin-13 or anti-interleukin-4), durations of study and severity of disease. Subgroup analysis based on category of T helper 2 (TH2) inflammation suggested greater efficacy in patients with higher levels of inflammatory biomarkers (blood eosinophils, exhaled nitric oxide and serum periostin). AUTHORS' CONCLUSIONS: Based on the totality of the evidence, compared with placebo, anti-interleukin-13/-4 agents are probably associated with a reduction in exacerbations requiring hospitalisation or ED visit, at the cost of increased adverse events, in patients with asthma. No clinically relevant improvements in health-related quality of life or asthma control were identified. Therefore, anti-interleukin-13 or anti-interleukin-4 agents may be appropriate for adults with moderate-to-severe uncontrolled asthma who have not responded to other treatments. These conclusions are generally supported by moderate or high-certainty evidence based on studies with an observation period of up to one year.

Coronavirus disease (COVID-19): An updated review based on current knowledge and existing literature for dermatologists.

The world entered the year 2020 with reports of the emergence of a new viral illness in Wuhan city, Hubei province, China. In January 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified to be the causative novel coronavirus for the cluster of patients suffering from pneumonia in China. The disease was later named as coronavirus disease (COVID-19) and was declared a pandemic by the World Health Organization on March 11, 2020. Several studies, since then, have tried to study and explain the origin of SARS-CoV-2, its structure and pathogenicity, epidemiology, modes of transmission, spectrum of illness and causes of mortality and morbidity. The current management strategies focus on supportive care and prevention of complications. With no definite treatment, as of now, encouraging reports of some anti-viral and anti-malarial drugs in the management of COVID-19 generate some hope. This review intends to cover the current known aspects of COVID-19 and SARS-CoV-19, based on the available literature.

Membrane-bound and soluble forms of an NMDA receptor extracellular domain retain epitopes targeted in auto-immune encephalitis.

BACKGROUND: Anti-NMDA receptor encephalitis (ANRE) is a potentially lethal disease attributed to auto-antibodies against the N-methyl-D-aspartate receptor (NMDAR). Full recovery is possible if therapy is initiated early in the disease course. Detection of ANRE antibodies in the cerebrospinal fluid (CSF) is essential for diagnosis. The assays for ANRE-associated IgGs often rely on cells transiently transfected with NMDAR genes. A cell line that stably expresses pathogenic NMDAR epitopes could improve standardization of the assays and provide antigen that could be used in commercial solid state assay systems. RESULTS: We expressed the amino terminal domain (ATD) of the GluN1 NMDAR subunit (NR1) as a fusion protein on the outer plasma membrane of 293T cells, creating a stable cell population (293T-ATD) that is recognized by ANRE patient monoclonal antibodies in flow cytometry and immunofluorescence assays. The ATD fusion protein also contains a Myc tag and a 6XHIS tag, which provide functionality for immunoassays and antigen purification, and a TEV protease site, which allows the ATD domain to be specifically released from the cells in essentially pure form. ATD mobilized from the 293T ATD cell line maintained the pathogenic ANRE epitopes in ELISA binding assays. CSF (3/4) and sera (4/4) from ANRE patients also bound the 293T-ATD cell line, whereas normal CSF and sera did not. CONCLUSIONS: The 293T-ATD cell line is potentially adaptable to a variety of formats to identify antibodies associated with ANRE, including cell-based and soluble antigen formats, and demonstrates a useful method to produce complex proteins for research, drug discovery, and clinical diagnosis.

Interrupting Base-Mediated Benzofuran Ring Transformation with Michael Acceptors.

A simple two-stage approach for the synthesis of 3-(2-arylbenzofuran-3-yl)propanoates and propanamides has been developed employing simple acrylates and acrylamides and readily available 3-aroylbenzofurans. The key step of this process involves a base-mediated ring opening of the 3-aroylbenzofurans and subsequent Michael addition of the resulting 1,3-dicarbonyl intermediate with acrylate/acrylamide, followed by the deformylation in one-pot. The resulting products undergo an acid-mediated dehydrative cyclization to arrive at these targets.

Identification and characterization of novel small molecule inhibitors of the acetyltransferase activity of Escherichia coli N-acetylglucosamine-1-phosphate-uridyltransferase/glucosamine-1-phosphate-acetyltransferase (GlmU).

This study aims at identifying novel chemical scaffolds as inhibitors specific to the acetyltransferase domain of a bifunctional enzyme, Escherichia coli GlmU, involved in the cell wall biosynthesis of Gram-negative organisms. A two-pronged approach was used to screen a 50,000 small-molecule library. Using the first approach, the library was in silico screened by docking the library against acetyltransferase domain of E. coli GlmU studies. In the second approach, complete library was screened against Escherichia coli ATCC 25922 to identify the whole cell active compounds. Active compounds from both the screens were screened in a colorimetric absorbance-based assay to identify inhibitors of acetyltransferase domain of E. coli GlmU which resulted in the identification of 1 inhibitor out of 56 hits identified by in silico screening and 4 inhibitors out of 35 whole cell active compounds on Gram-negative bacteria with the most potent inhibitor showing IC50 of 1.40 ± 0.69 µM. Mode of inhibition studies revealed these inhibitors to be competitive with AcCoA and uncompetitive with GlcN-1-P. These selected inhibitors were also tested for their antibacterial and cytotoxic activities. Compounds 5175178 and 5215319 exhibited antibacterial activity that co-related with GlmU inhibition. These compounds, therefore, represent novel chemical scaffolds targeting acetyltransferase activity of E. coli GlmU.

Patients' and healthcare providers' perceptions of a mobile portal application for hospitalized patients.

BACKGROUND: Hospital-based patient portals have the potential to better inform and engage patients in their care. We sought to assess patients' and healthcare providers' perceptions of a hospital-based portal and identify opportunities for design enhancements. METHODS: We developed a mobile patient portal application including information about the care team, scheduled tests and procedures, and a list of active medications. Patients were offered use of tablet computers, with the portal application, during their hospitalization. We conducted semi-structured interviews of patients and provider focus groups. Text from transcribed interviews and focus groups was independently coded by two investigators using a constant comparative approach. Codes were reviewed by a third investigator and discrepancies resolved via consensus. RESULTS: Overall, 18 patients completed semi-structured interviews and 21 providers participated in three focus groups. Patients found information provided by the portal to be useful, especially regarding team members and medications. Many patients described frequent use of games and non-clinical applications and felt the tablet helped them cope with their acute illness. Patients expressed a desire for additional detail about medications, test results, and the ability to record questions. Providers felt the portal improved patient engagement, but worried that additional features might result in a volume and complexity of information that could be overwhelming for patients. Providers also expressed concern over an enhanced portal's impact on patient-provider communication and workflow. CONCLUSIONS: Optimizing a hospital-based patient portal will require attention to type, timing and format of information provided, as well as the impact on patient-provider communication and workflow.

Male-female patient differences in the association between end-of-life discussions and receipt of intensive care near death.

BACKGROUND: Patient gender plays a significant role in patient-physician communication, patients' understanding of illness, and the aggressiveness of end-of-life (EoL) care. However, little is known about the extent to which gender differences in the effects of EoL discussions on EoL care contribute to gender differences in EoL care. The current study was aimed at determining whether gender differences exist in the receipt of intensive care unit (ICU) care near death and in the association between EoL discussions and the receipt of EoL ICU care. METHODS: This was a multisite, prospective cohort study of patients (n = 353) with metastatic cancers who were identified as terminally ill at study enrollment and were interviewed at a median of 4.1 months before their deaths. Postmortem chart reviews and caregiver interviews documented ICU stays in the last week of life. RESULTS: Patients who received ICU care at the EoL were more likely to be male than those who did not (73% vs 52%, P = .02). After adjustments for potential confounders, male patients reporting an EoL discussion were less likely to have an ICU stay in the last week of life than male patients with no EoL discussion (adjusted odds ratio, 0.26, 95% confidence interval, 0.07-0.91; P = .04). There was no association between EoL discussions and ICU stays near death among female patients. CONCLUSIONS: Men with advanced cancers are more likely than women to receive aggressive, nonbeneficial ICU care near death. Gender differences in the effects of EoL discussions on EoL care likely contribute to and may even explain gender differences in the receipt of ICU care in the last week of life.

Unpacking resident-led code status discussions: results from a mixed methods study.

BACKGROUND: The quality of code status discussions (CSDs) is suboptimal as physicians often fail to discuss patients' goals of care and resuscitation outcomes. We previously demonstrated that internal medicine residents randomized to a communication skills intervention scored higher than controls on a CSD checklist using a standardized patient. However, the impact of this training on CSD content is unknown. OBJECTIVE: Compare CSD content between intervention and control residents. DESIGN: We conducted qualitative analysis of simulated CSDs. Augmenting a priori codes with constant comparative analysis, we identified key themes associated with resident determination of code status. We dichotomized each theme as present or absent. We used chi-square tests to evaluate the association between training and presence of each theme. PARTICIPANTS: Fifty-six residents rotating on the internal medicine service in July 2010 were randomized to intervention (n = 25) or control (n = 31). INTERVENTION: Intervention residents completed CSD skills training (lectures, deliberate practice, and self-study). Six months later, all 56 residents completed a simulated CSD. MAIN MEASURE: Comparison of key themes identified in CSDs among intervention and controls. KEY RESULTS: Fifty-one transcripts were recorded and reviewed. Themes identified included: exploration of patient values/goals, framing code status as a patient decision, discussion of resuscitation outcomes and quality of life, and making a recommendation regarding code status. Intervention residents were more likely than controls to explore patient values/goals (p = 0.002) and make a recommendation (p < 0.001); and less likely to frame the decision as one solely to be made by the patient (p = 0.01). Less than one-third of residents discussed resuscitation outcomes or quality of life. CONCLUSION: Training positively influenced CSD content in key domains, including exploration of patient values/goals, making a recommendation regarding code status, and not framing code status as solely a patient decision. However, despite the intervention, residents infrequently discussed resuscitation outcomes and quality of life.

Triazino indole-quinoline hybrid: a novel approach to antileishmanial agents.

A novel series of 1,2,4-triazino-[5,6b]indole-3-thione covalently linked to 7-chloro-4-aminoquinoline have been synthesized and evaluated for their in vitro activity against extracellular promastigote and intracellular amastigote form of Leishmania donovani. Among all tested compounds, compounds 7a and 7b were found to be the most active with IC50 values 1.11, 0.36µM and selectivity index (SI) values 67, >1111, respectively, against amastigote form of L. donovani which is several folds more potent than the standard drugs, miltefosine (IC50=8.10µM, SI=7) and sodium stibo-gluconate (IC50=54.60µM, SI⩾7).

Synthesis and anti-proliferative activities of new derivatives of embelin.

Embelin (1), a benzoquinone isolated from Embelia ribes is known to possess variety of biological activities. Despite of several promising biological activities, preclinical efforts on embelin were hampered because of its poor aqueous solubility. In order to address the solubility issue, herein, we have synthesized a series of Mannich products of embelin by treating it with various secondary amines. The synthesized compounds were screened for antiproliferative and antimicrobial activities. In cytotoxicity screening, the benzyl-piperidine linked derivative 8m was found to possess better antiproliferative activity compared to parent natural product embelin against a panel of cell lines including HCT-116, MCF-7, MIAPaCa-2 and PC-3 with IC50 values of 30, 41, 34 and 36 µM, respectively. The mechanistic study of compound 8m revealed that it exhibits cytotoxicity via induction of apoptosis and mitochondrial membrane potential loss. Further, the compounds were tested for antimicrobial activity where dimethylamino- 8a and piperidine linked derivative 8b displayed antibacterial activity against Staphylococcus aureus with MIC values of 8 and 16 µg/mL, respectively. Mannich derivatives did now show improved aqueous solubility, however their hydrochloride salts 8a·HCl, 8b·HCl and 8m·HCl showed significantly improved aqueous solubility without affecting biological activities of parent Mannich derivatives.

The significance of persisters in tuberculosis drug discovery: Exploring the potential of targeting the glyoxylate shunt pathway.

The significant challenge in confronting TB eradication is the discursive treatment that results in the disease reactivation, patient non compliance and drug resistance. The presently available drug regimen for TB largely targets the active bacilli and thus remains inadequate against the dormant or persistent subpopulation of Mtb that results in latent TB affecting a quarter of the global population. The crucial pathways that are particularly essential for the survival of dormant Mtb demand better apprehension. Novel drugs are needed to specifically address these persisters in order to enhance treatment effectiveness. Among such pathways, the glyoxylate bypass plays a critical role in the persistence and latent infection of Mtb, making it a promising target for drug development in recent years. In this review, we have compiled the attributes of bacterial subpopulations liable for latent TB and the pathways indispensable for their survival. Specifically, we delve into the glyoxylate shunt pathway and its key enzymes as potential drug targets.