Multistate Outbreak of Melioidosis Associated with Imported Aromatherapy Spray.

Melioidosis, caused by the bacterium Burkholderia pseudomallei, is an uncommon infection that is typically associated with exposure to soil and water in tropical and subtropical environments. It is rarely diagnosed in the continental United States. Patients with melioidosis in the United States commonly report travel to regions where melioidosis is endemic. We report a cluster of four non-travel-associated cases of melioidosis in Georgia, Kansas, Minnesota, and Texas. These cases were caused by the same strain of B. pseudomallei that was linked to an aromatherapy spray product imported from a melioidosis-endemic area.

Performance of 21 Early Warning System scores in predicting in-hospital deterioration among undifferentiated admitted patients managed by ambulance services.

BACKGROUND: The optimal Early Warning System (EWS) scores for identifying patients at risk of clinical deterioration among those transported by ambulance services remain uncertain. This retrospective study compared the performance of 21 EWS scores to predict clinical deterioration using vital signs (VS) measured in the prehospital or emergency department (ED) setting. METHODS: Adult patients transported to a single ED by ambulances and subsequently admitted to the hospital between 1 January 2019 and 18 April 2019 were eligible for inclusion. The primary outcome was 30-day mortality; secondary outcomes included 3-day mortality, admission to intensive care or coronary care units, length of hospital stay and emergency call activations. The discriminative ability of the EWS scores was assessed using the area under the receiver operating characteristic curve (AUROC). Subanalyses compared the performance of EWS scores between surgical and medical patient types. RESULTS: Of 1414 patients, 995 (70.4%) (53.1% male, mean age 68.7±17.5 years) were included. In the ED setting, 30-day mortality was best predicted by VitalPAC EWS (AUROC 0.71, 95% CI (0.65 to 0.77)) and National Early Warning Score (0.709 (0.65 to 0.77)). All EWS scores calculated in the prehospital setting had AUROC <0.70. Rapid Emergency Medicine Score (0.83 (0.73 to 0.92)) and New Zealand EWS (0.88 (0.81 to 0.95)) best predicted 3-day mortality in the prehospital and ED settings, respectively. EWS scores calculated using either prehospital or ED VS were more effective in predicting 3-day mortality in surgical patients, whereas 30-day mortality was best predicted in medical patients. Among the EWS scores that achieved AUROC ≥0.70, no statistically significant differences were detected in their discriminatory abilities to identify patients at risk of clinical deterioration. CONCLUSIONS: EWS scores better predict 3-day as opposed to 30-day mortality and are more accurate when estimated using VS measured in the ED. The discriminatory performance of EWS scores in identifying patients at higher risk of clinical deterioration may vary by patient type.

Patterns of Mental Health Service Utilisation: A Population-Based Linkage of Over 17 Years of Health Administrative Records.

A cross-sectoral partnership was formed in 2021 in support of the recommendations in an audit on access to state-funded mental health services. In this first paper, we aimed to describe the demographic and service utilisation of adults with a mental health diagnosis in the Western Australian state-funded health system from 2005 to 2021. Inpatient, emergency department, specialised (ambulatory) community mental health service, and death records were linked in individuals aged ≥ 18 years with a mental health diagnosis in Western Australia. Altogether, 392,238 individuals with at least one mental health service contact between 1st January 2005 and 31st December 2021 were included for analysis. Females, Aboriginal and/or Torres Strait Islander people, and those who lived outside major cities or in the most disadvantaged areas were more likely to access state-funded mental health services. While the number of individuals who accessed community mental health services increased over time (from 28,769 in 2005 to 50,690 in 2021), the percentage increase relative to 2005 was notably greater for emergency department attendances (127% for emergency department; 76% for community; and 63% for inpatient). Conditions that contributed to the increase for emergency department were mainly alcohol disorder, reaction to severe stress and adjustment disorders, and anxiety disorders. Sex differences were observed between conditions. The pattern of access increased for emergency department and the community plus emergency department combination. This study confirmed that the patterns of access of state-funded mental health services have changed markedly over time and the potential drivers underlying these changes warrant further investigation.

How executive functioning, sentence processing, and vocabulary are related at 3 years of age.

There is a wealth of evidence demonstrating that executive function (EF) abilities are positively associated with language development during the preschool years, such that children with good executive functions also have larger vocabularies. However, why this is the case remains to be discovered. In this study, we focused on the hypothesis that sentence processing abilities mediate the association between EF skills and receptive vocabulary knowledge, in that the speed of language acquisition is at least partially dependent on a child's processing ability, which is itself dependent on executive control. We tested this hypothesis in longitudinal data from a cohort of 3- and 4-year-old children at three age points (37, 43, and 49 months). We found evidence, consistent with previous research, for a significant association between three EF skills (cognitive flexibility, working memory [as measured by the Backward Digit Span], and inhibition) and receptive vocabulary knowledge across this age range. However, only one of the tested sentence processing abilities (the ability to maintain multiple possible referents in mind) significantly mediated this relationship and only for one of the tested EFs (inhibition). The results suggest that children who are better able to inhibit incorrect responses are also better able to maintain multiple possible referents in mind while a sentence unfolds, a sophisticated sentence processing ability that may facilitate vocabulary learning from complex input.

Complementary and Alternative Medicine: Consumers' Experience With Food Therapy in Traditional Chinese Medicine in Hong Kong.

Context: The trend of people using complementary and alternative medicine (CAM) has been increasing globally. To enact policies and regulations that promote the safe use of CAM, a detailed investigation is needed into people's knowledge, practices, and beliefs related to CAM. Food therapy has long been regarded as an important part of traditional Chinese medicine (TCM), a type of CAM. Objective: This study intended to empirically examine the public's knowledge about TCM food therapy, including the sources of that knowledge, actual practices, and the public's beliefs about the therapy. Design: The research team designed a questionnaire to test the public's understanding of food properties as designated in TCM food therapy and to identify the public's sources of knowledge and experience in using food therapy. Setting: The study took place at the College of Professional and Continuing Education, the Hong Kong Polytechnic University, and the University of Hong Kong in Hong Kong, China. Participants: Participants were 447 Chinese students participating in postsecondary or tertiary education at the two higher education institutions mentioned above. Outcome Measures: The survey's quantitative questions examined respondents' prior TCM knowledge, sources of knowledge, and food therapy experience compared to their ability to correctly categorize 24 foods. The survey's qualitative questions examined the general practice of food therapy and the cultural beliefs underlying the food therapy strategies that participants used. Results: The study showed that: (1) having prior and partial knowledge of food properties (P = .000); (2) seeking information from the internet (P = .000), television (P = .0473) and friends (P = .0181); and (3) having used food therapy for chronic conditions (P = .0034) significantly improved participants ability to correctly categorize foods as to their food therapy characteristics. Conclusions: Participants relied less on traditional medical sources such as parents and health professionals but more on the internet, which may have empowered them through wider access to information. The study has further contributed to the study of Complementary and Alternative Medicine (CAM) by highlighting the role of cultural practices and beliefs in TCM food therapy.

Patient Use, Experience, and Satisfaction With Telehealth in an Australian Population (Reimagining Health Care): Web-Based Survey Study.

BACKGROUND: The COVID-19 pandemic triggered a rapid scale-up of telehealth services in Australia as a means to provide continued care through periods of physical restrictions. The factors that influence engagement in telehealth remain unclear. OBJECTIVE: The purpose of this study is to understand the experience of Australian people who engaged in a telehealth consultation during the pandemic period (2020-2021) and the demographic factors that influence engagement. METHODS: A web-based survey was distributed to Australians aged over 18 years that included 4 questions on frequency and type of clinical consultation, including with a general practitioner (GP), specialist, allied health, or nurse; 1 question on the experience of telehealth; and 2 questions on the quality of and satisfaction with telehealth. Statistical analysis included proportion of responses (of positive responses where a Likert scale was used) and regression analyses to determine the effect of demographic variables. RESULTS: Of the 1820 participants who completed the survey, 88.3% (1607/1820) had engaged in a health care consultation of some type in the previous 12 months, and 69.3% (1114/1607) of those had used telehealth. The most common type of consultation was with a GP (959/1114, 86.1%). Older people were more likely to have had a health care consultation but less likely to have had a telehealth consultation. There was no difference in use of telehealth between metropolitan and nonmetropolitan regions; however, people with a bachelor's degree or above were more likely to have used telehealth and to report a positive experience. A total of 87% (977/1114) of participants agreed or strongly agreed that they had received the information they required from their consultation, 71% (797/1114) agreed or strongly agreed that the outcome of their consultation was the same as it would have been face-to-face, 84% (931/1114) agreed or strongly agreed that the doctor or health care provider made them feel comfortable, 83% (924/1114) agreed or strongly agreed that the doctor or health care provider was equally as knowledgeable as providers they have seen in person; 57% (629/1114) of respondents reported that they would not have been able to access their health consultation if it were not for telehealth; 69% (765/1114) of respondents reported that they were satisfied with their telehealth consultation, and 60% (671/1114) reported that they would choose to continue to use telehealth in the future. CONCLUSIONS: There was a relatively high level of engagement with telehealth over the 12 months leading up to the study period, and the majority of participants reported a positive experience and satisfaction with their telehealth consultation. While there was no indication that remoteness influenced telehealth usage, there remains work to be done to improve access to older people and those with less than a bachelor's degree.

A qualitative study of services accessibility for indigenous persons who use injection drugs across three communities in the United States.

Aims: This study concerns the perspectives of Indigenous persons who use injection drugs (IPWIDs) and key stakeholders across multiple sectors regarding healthcare service and treatment accessibility in the United States.Methods: Sixty in-depth interviews were undertaken with selected participants (30 people who use injection drugs and 30 stakeholders) across three non-urban locations in the United States. An inductive analytic approach was used to explore perspectives regarding healthcare accessibility gaps.Results: IPWIDs described injecting stimulants, opioids, and diverted medications for opioid use disorder, as well as having unstable access to sterile syringes. Often, the most accessible treatment for IPWID substance use was engagement with punitive aspects of the criminal justice system. While local health and social services were described as providing limited or inadequate services for IPWIDs, human capital deficiencies in those agencies and institutions often reinforced barriers to accessibility for IPWIDs, further aggravating the epidemics of Hepatitis C Virus infection and overdose risk in Indigenous communities. Conclusions: Decolonizing approaches to IPWID-centered services are urgently needed to reduce disparities in transmission of infectious diseases and other health consequences of injection drug use among American Indian people. Potential pathways forward include moving away from punitive treatment of IPWIDs by the criminal justice system and toward local, tribally-centered, culturally appropriate treatment models. We identify an urgent need to provide reliable and local access to sterile injection equipment and opioid substitution treatment on or near reservations.

Comparing reliability of ICD-10-based COVID-19 comorbidity data to manual chart review, a retrospective cross-sectional study.

International Statistical Classification of Disease and Related Health Problems, 10th Revision codes (ICD-10) are used to characterize cohort comorbidities. Recent literature does not demonstrate standardized extraction methods. OBJECTIVE: Compare COVID-19 cohort manual-chart-review and ICD-10-based comorbidity data; characterize the accuracy of different methods of extracting ICD-10-code-based comorbidity, including the temporal accuracy with respect to critical time points such as day of admission. DESIGN: Retrospective cross-sectional study. MEASUREMENTS: ICD-10-based-data performance characteristics relative to manual-chart-review. RESULTS: Discharge billing diagnoses had a sensitivity of 0.82 (95% confidence interval [CI]: 0.79-0.85; comorbidity range: 0.35-0.96). The past medical history table had a sensitivity of 0.72 (95% CI: 0.69-0.76; range: 0.44-0.87). The active problem list had a sensitivity of 0.67 (95% CI: 0.63-0.71; range: 0.47-0.71). On day of admission, the active problem list had a sensitivity of 0.58 (95% CI: 0.54-0.63; range: 0.30-0.68)and past medical history table had a sensitivity of 0.48 (95% CI: 0.43-0.53; range: 0.30-0.56). CONCLUSIONS AND RELEVANCE: ICD-10-based comorbidity data performance varies depending on comorbidity, data source, and time of retrieval; there are notable opportunities for improvement. Future researchers should clearly outline comorbidity data source and validate against manual-chart-review.

Association of race/ethnicity and socioeconomic status with COVID-19 30-day mortality at a Philadelphia medical center using a retrospective cohort study.

COVID-19 has disproportionately affected low-income communities and people of color. Previous studies demonstrated that race/ethnicity and socioeconomic status (SES) are not independently correlated with COVID-19 mortality. The purpose of our study is to determine the effect of race/ethnicity and SES on COVID-19 30-day mortality in a diverse, Philadelphian population. This is a retrospective cohort study in a single-center tertiary care hospital in Philadelphia, PA. The study includes adult patients hospitalized with polymerase-chain-reaction-confirmed COVID-19 between March 1, 2020 and June 6, 2020. The primary outcome was a composite of COVID-19 death or hospice discharge within 30 days of discharge. The secondary outcome was intensive care unit (ICU) admission. The study included 426 patients: 16.7% died, 3.3% were discharged to hospice, and 20.0% were admitted to the ICU. Using multivariable analysis, race/ethnicity was not associated with the primary nor secondary outcome. In Model 4, age greater than 75 (odds ratio [OR]: 11.01; 95% confidence interval [CI]: 1.96-61.97) and renal disease (OR: 2.78; 95% CI: 1.31-5.90) were associated with higher odds of the composite primary outcome. Living in a "very-low-income area" (OR: 0.29; 95% CI: 0.12-0.71) and body mass index (BMI) 30-35 (OR: 0.24; 95% CI: 0.08-0.69) were associated with lower odds of the primary outcome. When controlling for demographics, SES, and comorbidities, race/ethnicity was not independently associated with the composite primary outcome. Very-low SES, as extrapolated from census-tract-level income data, was associated with lower odds of the composite primary outcome.

Biology, Bias, or Both? The Contribution of Sex and Gender to the Disparity in Cardiovascular Outcomes Between Women and Men.

PURPOSE OF REVIEW: Cardiovascular disease (CVD) is the leading cause of mortality and morbidity worldwide for both men and women. However, CVD is understudied, underdiagnosed, and undertreated in women. This bias has resulted in women being disproportionately affected by CVD when compared to men. The aim of this narrative review is to explore the contribution of sex and gender on CVD outcomes in men and women and offer recommendations for researchers and clinicians. RECENT FINDINGS: Evidence demonstrates that there are sex differences (e.g., menopause and pregnancy complications) and gender differences (e.g., socialization of gender) that contribute to the inequality in risk, presentation, and treatment of CVD in women. To start addressing the CVD issues that disproportionately impact women, it is essential that these sex and gender differences are addressed through educating health care professionals on gender bias; offering patient-centered care and programs tailored to women's needs; and conducting inclusive health research.

Medium-Chain Triglyceride Oil and Blood Lipids: A Systematic Review and Meta-Analysis of Randomized Trials.

BACKGROUND: Dietary saturated fat raises total cholesterol and LDL cholesterol levels. It is unclear whether these effects differ by the fatty acid chain lengths of saturated fats; particularly, it is unclear whether medium-chain fatty acids increase lipid levels. OBJECTIVES: We conducted a systematic review to determine the effects of medium-chain triglyceride (MCT) oil, consisting almost exclusively of medium-chain fatty acids (6:0-10:0), on blood lipids. METHODS: We searched Medline and Embase through March 2020 for randomized trials with a minimum 2-week intervention period that compared MCT oil with another fat or oil. Outcomes were total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride levels. Included studies were restricted to adults above 18 years of age. Studies conducted in populations receiving enteral or parenteral nutrition were excluded. Data were pooled using a random-effects meta-analysis. RESULTS: Seven articles were included in the meta-analysis; LDL cholesterol and HDL cholesterol were reported in 6 studies. MCT oil intake did not affect total cholesterol (0.04 mmol/L; 95% CI, -0.11 to 0.20; I2 = 33.6%), LDL cholesterol (0.02 mmol/L; 95% CI, -0.13 to 0.17; I2 = 28.7%), or HDL cholesterol (-0.01 mmol/L; 95% CI, -0.10 to 0.09; I2 = 74.1%) levels, but did increase triglycerides (0.14 mmol/L; 95% CI, 0.01-0.27; I2 = 42.8%). Subgroup analyses showed that the effects of MCT oil on total cholesterol and LDL cholesterol differed based on the fatty acid profile of the control oil (Pinteraction = 0.003 and 0.008, respectively), with MCT oil increasing total cholesterol and LDL cholesterol when compared to a comparator consisting predominantly of unsaturated fatty acids, and with some evidence for reductions when compared to longer-chain SFAs. CONCLUSIONS: MCT oil does not affect total cholesterol, LDL cholesterol, or HDL cholesterol levels, but does cause a small increase in triglycerides.

Full-thickness macular holes after surgical repair of primary rhegmatogenous retinal detachments: incidence, clinical characteristics, and outcomes.

PURPOSE: Full-thickness macular hole (FTMH) formation following rhegmatogenous retinal detachment (RRD) repair may limit post-operative visual acuity and often requires a return to the operating room, but little is known about this phenomenon. METHODS: This study included all patients with a FTMH that developed after RRD repair from January 1, 2015-July 31, 2020. The main outcome was the rate of FTMH formation following RRD repair as well as characteristics of FTMH following RRD repair that spontaneously close. RESULTS: There were 470 eyes with a diagnosis of both a FTMH and a RRD during the study period. Of these, 27 (0.28%) developed a FTMH following RRD repair. The median time to FTMH diagnosis was 91 days (25th, 75th quartiles 40, 204 days). The mean minimum hole diameter was 514.5 ± 303.6 microns. There were 4 FTMHs (14.8%) that spontaneously closed without surgical intervention. The spontaneous closure was noted from 4 to 12 weeks after the initial diagnosis of the FTMH. These holes were smaller than the holes that did not close spontaneously (mean minimum diameter 161.8 ± 85.2 vs 588.7 ± 279.3 microns, p = 0.0058). Of the 27 post-operative FTMHs, there were 23 eyes (85%) that underwent surgical intervention with pars plana vitrectomy and internal limiting membrane peeling. Nineteen eyes (83%) closed with one surgery, 20 eyes (87%) ultimately closed, while 3 eyes (11.1%) did not close. CONCLUSIONS: FTMH is relatively uncommon to occur following RRD repair with a prevalence of 0.28% in our series with 87% of these holes achieving closure following surgery or spontaneously. Approximately 15% of FTMHs following RRD repair closed spontaneously and these holes were significantly smaller.

Where there's smoke, there's fire: what current and future providers do and do not know about electronic cigarettes.

BACKGROUND: Health care providers play a pivotal role as educators on health-related matters ranging from vaccination to smoking cessation. With the rising popularity of electronic cigarettes (e-cigarettes), providers face a new challenge. To date, studies have identified a general lack of knowledge among providers regarding e-cigarettes and discomfort with counseling patients on e-cigarette use. This study aims to systematically explore the perspectives of different health care providers on e-cigarettes and their health implications. With a growing availability of research on the health consequences of e-cigarette use, our study also aims to assess the familiarity of our participants with this literature. METHODS: From July to October 2018, a sample of attendings (n = 15), residents (n = 15), medical students (n = 33), and nursing students (n = 28) from Thomas Jefferson University participated in a freelisting interview and survey. RESULTS: Our study found that perceptions of e-cigarettes vary across different participant groups, as evidenced by the range of responses when asked to think about e-cigarettes and their health implications. We identified gaps in knowledge among students regarding FDA regulation of e-cigarettes and found that attending physicians are less aware than junior trainees of the prevalence of use. Familiarity with evidence-based health consequences was variable and low across all groups. Finally, participants most commonly reported learning about e-cigarettes from news outlets and social media rather than professional platforms. CONCLUSION: This study highlights the need for curricular development in nursing and medical schools, residency training, and continuing medical education regarding e-cigarette use and their impact on human health.

Identification of undocumented over-the-counter medications in an academic nephrology clinic.

OBJECTIVES: To explore how accurately over-the-counter (OTC) medications were documented in an academic nephrology clinic and the benefits of using a novel short questionnaire as part of medication reconciliation (MR). METHODS: We developed a 3-item tailored questionnaire with questions about use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and proton pump inhibitors (PPIs), which clinical leadership identified as medications of interest. Over the course of 20 days, medical assistants administered the questionnaire to clinic patients immediately after the standard MR. We summarized the rate of inaccurate medication documentation by individual drug and drug class, comparing the standard MR process with the questionnaire. We also calculated diagnostic performance characteristics of the questionnaire. We evaluated the severity of drug-drug interactions between OTC medications discovered using the OTC medication questionnaire and patients' other prescription medications. RESULTS: Nearly 30% (n = 133 of 450) of the participants had at least 1 inaccurately documented OTC medication after the standard MR. The sensitivity and specificity of the standard MR were 79.2% and 93.5%, respectively, for aspirin; 14.5% and 99.5% for NSAIDs; and 80.4% and 97.3% for PPIs. Medication omissions were resolved in the electronic health record approximately two-thirds of the time using the questionnaire. At least 1 drug-drug interaction (DDI) involving active use of an OTC medication was identified in 9.6% of the patients. Of the DDIs, the most common portended effects were increased nephrotoxicity (52.9%), increased bleeding risk (22.9%), and enhanced antiplatelet activity (7.1%). CONCLUSION: Despite the standard MR process, inaccurate documentation of commonly used OTC medications occurred in nearly one-third of outpatients in a nephrology clinic. A brief OTC medication questionnaire may be a scalable and effective strategy to address this problem.

Mutagenesis of FAD2 genes in peanut with CRISPR/Cas9 based gene editing.

BACKGROUND: Increasing the content of oleic acid in peanut seeds is one of the major goals in peanut breeding due to consumer and industry benefits, such as anti-oxidation and long shelf-life. Homeologous ahFAD2A and ahFAD2B genes encode fatty acid desaturases, which are the key enzymes for converting oleic acid to linoleic acid that oxidizes readily. To date, all high oleic acid peanut varieties result from natural mutations occurred in both genes. A method to induce mutations in the genes of other elite cultivars could speed introgression of this valuable trait. The gene-editing approach utilizing CRISPR/Cas9 technology was employed to induce de novo mutations in the ahFAD2 genes using peanut protoplasts and hairy root cultures as models. RESULTS: The hot spot of natural mutation in these genes was selected as the target region. Appropriate sgRNAs were designed and cloned into a CRISPR/Cas9 expression plasmid. As a result of CRISPR/Cas9 activity, three mutations were identified - G448A in ahFAD2A, and 441_442insA and G451T in ahFAD2B. The G448A and 441_442insA mutations are the same as those seen in existing high oleate varieties and the G451T is new mutation. Because natural mutations appear more often in the ahFAD2A gene than in the ahFAD2B gene in subspecies A. hypogaea var. hypogaea, the mutations induced in ahFAD2B by gene editing may be useful in developing high oleate lines with many genetic backgrounds after validation of oleic acid content in the transformed lines. The appearance of the G448A mutation in ahFAD2A is a further benefit for high oleic acid oil content. CONCLUSIONS: Overall, these results showed that mutations were, for the first time, induced by CRISPR-based gene editing approach in peanut. This research demonstrated the potential application of gene editing for mutagenesis in peanut and suggested that CRISPR/Cas9 technology may be useful in the peanut breeding programs.

Public exposure and attitudes about homelessness.

In this study, we conducted a survey among a large sample of U.S. adults to assess attitudes and beliefs about the causes of homelessness, policies to address homelessness, and programs for homeless individuals. In 2016, we surveyed a national sample of 541 adults from 47 different U.S. states using Amazon Mechanical Turk. Of the total sample, 78% reported that homelessness was a problem in their communities and 60% believed homelessness would increase in the next 5 years. The majority expressed compassion for homeless individuals and endorsed structural, intrinsic, and health factors as causes of homelessness. Most participants (73%-88%) believed the federal government should dedicate more funds and policies for homeless individuals. These attitudes were substantially more likely to be reported by participants who were female, lower income, Democrat, and personally exposed to homelessness. Most Americans care about homelessness as a major problem but there are divergent perspectives on solutions to address homelessness based on gender, income level, and political affiliation.

Changes in Public Attitudes and Perceptions about Homelessness Between 1990 and 2016.

Public attitudes on homelessness can and has influenced policies and services for homeless populations. This study surveyed national public attitudes about homelessness in the 21st century and examined changes in attitudes in the past two decades. An online survey of public attitudes about homelessness was conducted with 541 U.S. adults across 47 states in November 2016 using Amazon Mechanical Turk. Survey results were compared to two public surveys conducted in 1990. Compared to previous surveys, the current sample endorsed more compassion, government support, and liberal attitudes about homelessness. The largest changes were related to increased support for homeless individuals to use public spaces for sleeping and panhandling. When asked about the demographic composition of the homeless population, the contemporary sample tended to overestimate the proportions who were young and racial/ethnic minorities, while underestimating the proportions who were married, or had mental health or substance abuse problems. Together, the findings suggest there has been an increase in compassion and liberal attitudes toward homelessness in the past two decades. Greater support for homeless individuals during an era of economic recessions and governmental homeless initiatives presents opportunities for new public health approaches to address homelessness.

Design, synthesis and in vitro cell-based evaluation of the anti-cancer activities of hispolon analogs.

Phytochemicals play an important role in cancer therapy. Hispolon and 26 of its analogs (9 known and 17 new) were synthesized and evaluated for their antiproliferative activities in a panel of six independent human cancer cell lines using the in vitro cell-based MTT assay. Among the hispolon analogs tested, compound VA-2, the most potent overall, produced its most significant effect in the colon cancer cell lines HCT-116 (IC50 1.4 ± 1.3 µM) and S1 (IC50 1.8 ± 0.9 µM) compared to its activity in the normal HEK293/pcDNA3.1 cell line (IC50 15.8±3.7 µM; p<0.01 for each comparison). Based on our results, VA-2 was about 9- to 11-times more potent in colon cancer cells and 2- to 3-times more potent in prostate cancer cells compared to HEK293/pcDNA3.1 cells. Morphological analysis of VA-2 showed significant reduction of cell number, while the cells' sizes were also markedly increased and were obvious at 68 h of treatment with 1 µM in HCT-116 (colon) and PC-3 (prostate) cancer cells. A known analog, compound VA-4, prepared by simple modifications on the aromatic functional groups of hispolon, inhibited prostate and colon cancer cell lines with IC50 values <10 µM. In addition, hispolon isoxazole and pyrazole analogs, VA-7 and VA-15 (known), respectively, have shown significant activity with the mean ICv values in the range 3.3-10.7 µM in all the cancer cell lines tested. Activity varied among the analogs in which aromatic functional groups and ß-diketone functional groups are modified. But the activity of analogs VA-16 to VA-27 was completely lost when the side chain double-bond was hydrogenated indicating the crucial role of this functionality for anticancer activity. Furthermore, many of the compounds synthesized were not substrates for the ABCB1-transporter, the most common cause of multidrug resistance in anti-cancer drugs, suggesting they may be more effective anticancer agents.

IND-2, a pyrimido[1″,2″:1,5]pyrazolo[3,4-b]quinoline derivative, circumvents multi-drug resistance and causes apoptosis in colon cancer cells.

Naturally occurring condensed quinolines have anticancer properties. In efforts to find active analogues, we designed and synthesized eight polycyclic heterocycles with a pyrimido[1″,2″:1,5]pyrazolo[3,4-b]quinoline framework (IND series). The compounds were evaluated for activity against colon (HCT-116 and S1-MI-80), prostate (PC3 and DU-145), breast (MCF-7 and MDAMB-231), ovarian (ov2008 and A2780), and hepatocellular (HepG2) cancer cells and against non-cancerous Madin Darby canine kidney (MDCK), mouse embryonic fibroblast (NIH/3T3), and human embryonic kidney cells (HEK293). IND-2, a 4-chloro-2-methyl pyrimido[1″,2″:1,5]pyrazolo[3,4-b]quinoline, exhibited more than ten-fold selectivity and potent cytotoxic activity against colon cancer cells relative to the other cancer and non-cancer cells. With five additional colon cancer cell lines (HT-29, HCT-15, LS-180, LS-174, and LoVo), IND-2 had similar cytotoxicity and selectivity, and sub-micromolar concentrations caused changes in the morphology of HCT-116 and HCT-15 cells. IND-2 did not activate the transactivating function of the pregnane X receptor (PXR), indicating that it does not induce PXR-regulated ABCB1 or ABCG2 transporters. Indeed, IND-2 was not a substrate of ABCB1 or ABCG2, and it induced cytotoxicity in HEK293 cells overexpressing ABCB1 or ABCG2 to the same extent as in normal HEK293 cells. IND-2 was cytotoxic to resistant colon carcinoma S1-MI-80 cells, approximately three- and five-fold more than SN-38 and topotecan, respectively. In HCT-116 colon cancer cells, IND-2 produced concentration-dependent changes in mitochondrial membrane potential, leading to apoptosis, and sub-micromolar concentrations caused chromosomal DNA fragmentation. These findings suggest that, by increasing apoptosis, IND-2 has potential therapeutic efficacy for colorectal cancer.

HbA1c, fasting and 2 h plasma glucose in current, ex- and never-smokers: a meta-analysis.

AIMS/HYPOTHESIS: The relationships between smoking and glycaemic variables have not been well explored. We compared HbA1c, fasting plasma glucose (FPG) and 2 h plasma glucose (2H-PG) in current, ex- and never-smokers. METHODS: This meta-analysis used individual data from 16,886 men and 18,539 women without known diabetes in 12 DETECT-2 consortium studies and in the French Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) and Telecom studies. Means of three glycaemic variables in current, ex- and never-smokers were modelled by linear regression, with study as a random factor. The I (2) statistic was used to evaluate heterogeneity among studies. RESULTS: HbA1c was 0.10% (95% CI 0.08, 0.12) (1.1 mmol/mol [0.9, 1.3]) higher in current smokers and 0.03% (0.01, 0.05) (0.3 mmol/mol [0.1, 0.5]) higher in ex-smokers, compared with never-smokers. For FPG, there was no significant difference between current and never-smokers (-0.004 mmol/l [-0.03, 0.02]) but FPG was higher in ex-smokers (0.12 mmol/l [0.09, 0.14]). In comparison with never-smokers, 2H-PG was lower (-0.44 mmol/l [-0.52, -0.37]) in current smokers, with no difference for ex-smokers (0.02 mmol/l [-0.06, 0.09]). There was a large and unexplained heterogeneity among studies, with I (2) always above 50%; I (2) was little changed after stratification by sex and adjustment for age and BMI. In this study population, current smokers had a prevalence of diabetes that was 1.30% higher as screened by HbA1c and 0.52% lower as screened by 2H-PG, in comparison with never-smokers. CONCLUSION/INTERPRETATION: Across this heterogeneous group of studies, current smokers had a higher HbA1c and lower 2H-PG than never-smokers. This will affect the chances of smokers being diagnosed with diabetes.