Targeted Anthocyanin Profiling of Fruits from Three Southern Highbush Blueberry Cultivars Propagated in Colombia.

The blueberry, a deciduous shrub in the Ericaceae family, is celebrated for its delightful flavor, sweetness, and abundance of anthocyanins and antioxidants, qualities that have garnered significant attention for their potential health benefits. Blueberries grown in diverse environments and exhibit varied anthocyanin profiles, often influenced by factors such as altitude and climate. Varietal groups worldwide have been bred and categorized based on their growth habits and specific cold requirements, particularly with southern highbush cultivars thriving in temperate climates, demonstrating tolerance to higher altitudes or cooler climates-a result of hybridizations involving various Vaccinium species. In the Colombian Andes, southern highbush blueberries thrive in unique high-altitude conditions, leading to exceptional quality due to the region's cool climate and specific soil characteristics. In this context, this study aimed to chemically characterize and differentiate three southern highbush blueberry cultivars (i.e., 'Biloxi,' 'Legacy' and 'Sharpblue') cultivated in a Colombian Andean plateau and compare them to three commercially available highbush blueberries. This comprehensive evaluation involved examining total phenols, flavonoids, anthocyanin content, and DPPH· free-radical scavenging capacity, as well as conducting anthocyanin-targeted profiling via HPLC-DAD-HRMS. Through supervised multivariate analyses such as sPLS-DA, this study delved into the pattern recognition of those anthocyanins that could potentially serve as markers for quality and cultivar-related chemical trait determination. These findings locate blueberry-derived anthocyanins in a metabolic context and afford some insights into southern highbush blueberry cultivar differentiation to be used for further purposes.

A qualitative study of stakeholder and researcher perspectives of community engagement practices for HIV vaccine clinical trials in South Africa.

Community engagement increases community trust of research and improves trial participation. However, there is limited documented appraisal of community engagement practices. Several HIV vaccine efficacy trials have been conducted in South Africa, the country most affected by HIV, predominantly in collaboration with the HIV Vaccine Trials Network (HVTN). We explored stakeholder and researcher perspectives of the HVTN community engagement practices used in the Gauteng province of South Africa. In 2017, we conducted a qualitative study. Using semi-structured interview guides, we facilitated two group discussions with Community Advisory Board (CAB) members (n = 13), and 14 in-depth interviews with HVTN-affiliated employees (n = 8 in South Africa and n = 6 in the USA). Group discussions and in-depth interviews were audio-recorded, transcribed verbatim, translated into English, and coded using NVIVO 12 Plus software for thematic data analysis. Overall, median age of study participants was 22 (interquartile range 32-54) years, and 74% (n = 20) were female. Three main themes about community engagement emerged: (i) community engagement as an ongoing iterative relationship between researchers and community; (ii) methods of community engagement, encompassing community education by linking with external stakeholders and through awareness campaigns by pamphlet distribution and mass events, working with communities to develop recruitment messages, and working with CAB as a link to communities; and (iii) strategies to improve community engagement, for example, using simple language, linking with religious leaders and traditional healers, and communicating via conventional (newspapers, television, and radio) and social (videos and listicles) media. Our data indicate ways for researchers to improve relationships with community by understanding local needs, strengthening collaborations, and tailoring communication strategies. In this regard, CABs signify critical linkages between researchers and communities. CABs can relay relevant health research needs, advise on the creation of suitable materials, and link researchers more effectively with community leaders and media.

Mental Health Service Utilization Among Medical Students with a Perceived Need for Care.

OBJECTIVE: The authors investigated levels of perceived need for help, patterns of mental health service utilization, and barriers to care among US medical students with a focus on students who perceived a need for help but did not report service use in the past 12 months. METHODS: The authors administered an online survey to 2,868 medical students at three schools in Ohio between January and February 2020 including validated scales for psychological distress, self-stigma, and an exploration of mental health treatment. The authors used multivariable logistic regression to identify factors associated with treatment and qualitative analysis to identify common barriers to care. RESULTS: Twenty-eight percent (N = 800) of 2,868 students responded to the survey. Fifty-six percent (n = 439) of students reported a perceived need for help, while 34.6% of these respondents (n = 152) did not receive treatment. Among those with perceived need who completed the survey (n = 388), Asian students compared to non-Hispanic white students (adjusted odds ratio [aOR] = 0.45, 95% confidence interval [CI] 0.25-0.82) and those with higher self-stigma (aOR = 0.90, 95% CI 0.87-0.94) had lower odds of service use. Students told by others to seek help (aOR = 2.82, 95% CI 1.71-4.64) were the only group with higher odds of service use. The most common barriers to care were lack of time, difficulty accessing services, and stigma. CONCLUSIONS: Despite a perceived need for help, many students do not seek care and experience treatment barriers. Schools can encourage help-seeking by identifying students in need, using targeted messaging, fostering a low-stigma environment, and removing barriers.

Functionally Significant Coumarin-Related Variant Alleles and Time to Therapeutic Range in Chilean Cardiovascular Patients.

Despite the development of new oral agents over the last decade, vitamin K antagonists (VKAs) remain the most widely used anticoagulants for treating and preventing thromboembolism worldwide. In Chile, the Ministry of Health indicates that acenocoumarol should be used in preference to any other coumarin. Complications of inappropriate dosing are among the most frequently reported adverse events associated with this medication. It is well known that polymorphisms in pharmacokinetic and pharmacodynamic proteins related to coumarins (especially warfarin) influence response to these drugs. This work analyzed the impact of CYP2C19*2 (rs4244285), CYP1A2*1F (rs762551), GGCx (rs11676382), CYP2C9*2 (rs1799853), CYP2C9*3 (rs1057910), CYP4F2 (rs2108622), VKORC1 (rs9923231), VKORC1 (rs7294), CYP3A4*1B (rs2740574), and ABCB1 (rs1045642) polymorphisms on time to therapeutic range for oral anticoagulants in 304 Chilean patients. CYP2C9*3 polymorphisms were associated with time to therapeutic range for acenocoumarol in Chilean patients, and the CYP4F2 TT genotype, MDR1 A allele, CYP1A2 A allele, and CYP3A4T allele are promising variants that merit further analysis. The presence of polymorphisms explained only 4.1% of time to therapeutic range for acenocoumarol in a multivariate linear model. These results improve our understanding of the basis of ethnic variations in drug metabolism and response to oral anticoagulant therapy. We hope that these findings will contribute to developing an algorithm for VKA dose adjustment in the Chilean population in the near future, decreasing the frequency of stroke, systemic embolism, and bleeding-related adverse events.

A Pharmacogenetically Guided Acenocoumarol Dosing Algorithm for Chilean Patients: A Discovery Cohort Study.

BACKGROUND: Vitamin K antagonists (VKA) are used as prophylaxis for thromboembolic events in patients with cardiovascular diseases. The most common VKA are warfarin and acenocoumarol. These drugs have a narrow therapeutic margin and high inter-individual response variability due to clinical and pharmacogenetic variables. OBJECTIVE: The authors aim to develop an algorithm comprised of clinical and genetic factors to explain the variability in the therapeutic dose of acenocoumarol among Chilean patients. METHODOLOGY: DNA was obtained from 304 patients as a discovery cohort with an international normalized ratio (INR) range of 2.0-3.0. The non-genetic (demographic and clinical) variables were also recorded. Genotype analyses were performed using real-time PCR for VKORC1 (rs9923231), VKORC1 (rs7294), GGCx (rs11676382), CYP4F2 (rs2108622), ABCB1 (rs1045642), CYP2C9*2 (rs1799853), ApoE (rs429358), and CYP2C9*3 (rs1057910). RESULTS: The clinical variables that significantly influenced the weekly therapeutic dose of VKA were age, sex, body mass index (BMI), and initial INR, collectively accounting for 19% of the variability, and the genetic variables with a significant impact were VKORC1 (rs9923231), CYP2C9*2 (rs1799853), and CYP2C9*3 (rs1057910), explaining for another 37% of the variability. CONCLUSION: We developed an algorithm that explains 49.99% of the variability in therapeutic VKA dosage in the Chilean population studied. Factors that significantly affected the dosage included VKORC1, CYP2C9*2, and CYP2C9*3 polymorphisms, as well as age, sex, BMI, and initial INR.

Estudio comparativo de equipos INR capilar "point of care" versus INR venoso, en pacientes en tratamiento con antagonistas de vitamina K / Comparison of point of care capillary international normalized ratio (INR) with INR measured in venous samples

Background: INR is used to monitor the treatment with vitamin K antagonists. A strategy to reduce waiting times for sampling is to measure INR in a capillary sample using a portable point of care (POC) type coagulometer. Aim: To evaluate the correlation of CoaguChek Pro II™, Xprecia™ and microINR™ with venous INR measured at the clinical laboratory and their ease of use. Materials and Methods: Patients provided capillary and venous blood samples for parallel tests comparing Xprecia™ Stride with CoaguChek Pro II™ and with venous INR, microINR™ with CoaguChek Pro IITM and with venous INR. The devices' ease of use was assessed surveying the sampling staff. Results: The three tested devices had good correlation coefficients with venous INR: CoaguChek Pro IITM 0.953 and 0.962; Xprecia™ of 0.912 and microINR™ of 0.932. The correlation coefficient of Xprecia™ with CoaguChek Pro IITM was 0.937 and microINR™ with CoaguChek Pro IITM was 0.976. Conclusions: CoaguChek Pro IITM, Xprecia™ and microINR™ results had a good correlation coefficient with INR measured at the laboratory. Our results indicate that, in the hands of trained users, POC-type coagulometers are reliable and acceptable for routine use in anticoagulant treatment control.

[Comparison of point of care capillary international normalized ratio (INR) with INR measured in venous samples]. / Estudio comparativo de equipos INR capilar "point of care" versus INR venoso, en pacientes en tratamiento con antagonistas de vitamina K.

BACKGROUND: INR is used to monitor the treatment with vitamin K antagonists. A strategy to reduce waiting times for sampling is to measure INR in a capillary sample using a portable point of care (POC) type coagulometer. AIM: To evaluate the correlation of CoaguChek Pro II™, Xprecia™ and microINR™ with venous INR measured at the clinical laboratory and their ease of use. MATERIALS AND METHODS: Patients provided capillary and venous blood samples for parallel tests comparing Xprecia™ Stride with CoaguChek Pro II™ and with venous INR, microINR™ with CoaguChek Pro IITM and with venous INR. The devices' ease of use was assessed surveying the sampling staff. RESULTS: The three tested devices had good correlation coefficients with venous INR: CoaguChek Pro IITM 0.953 and 0.962; Xprecia™ of 0.912 and microINR™ of 0.932. The correlation coefficient of Xprecia™ with CoaguChek Pro IITM was 0.937 and microINR™ with CoaguChek Pro IITM was 0.976. CONCLUSIONS: CoaguChek Pro IITM, Xprecia™ and microINR™ results had a good correlation coefficient with INR measured at the laboratory. Our results indicate that, in the hands of trained users, POC-type coagulometers are reliable and acceptable for routine use in anticoagulant treatment control.

Caracterización de muestras de cocaína inorgánica en una provincia ecuatoriana / Characterization of inorganic cocaine samples in an Ecuadorian province

El consumo de cocaína representa un problema de salud, por constituir un psicotrópico ilícito de elevado consumo, lo que ocasiona motivo de atención en los servicios de emergencia, adicción que genera riesgos relativos a los componentes asociados a la misma. Se realizó un estudio cuantitativo, de tipo descriptivo, cuyo objetivo fue caracterizar muestras inorgánicas de cocaína en el Laboratorio de Química Forense de una provincia del contexto ecuatoriano durante el período julio y diciembre de 2016. Se trabajó con la totalidad de la población, la que estuvo compuesta por 90 muestras. La cuantificación de los elementos químicos presen-tes en los ejemplares se realizó a través de una cromatografía de gases utilizando un detector de masas acoplado al equipo. Se determinó que de forma mayoritaria la mitad de las muestras contenían impurezas como cinamoilcocaína, metilecgonina, tropococaína, benzoilecgonina, kientras que solo el 11,1% de estas no tenía contaminaciones alcaloidales. En cuanto a la presencia de adulterantes en el material analizado, el almidón resultó ser el más utilizado por los comercializadores de la cocaína en el entorno estudiado; aunque también se pudo obser-var el uso de fenacetina, levamisol y aminopirina.

Consumption of cocaine represents an emerging health problem because it is an illicit psychotropic drug consumed among patients treated in emergency rooms, and it also genera-tes other risks related to the components that may be present in it. The study was carried out with a quantitative, descriptive approach. The research aimed to characterize the inorganic samples of cocaine in the Forensic Chemistry Laboratory of a province in the Ecuadorian context during the period July-December 2016. The whole population of 90 samples was taken into account. The quantification of the chemical elements presented in the specimens was carried out through gas chromatography using a mass detector coupled to the equipment. It was determined that half of the samples contained impurities sucah as cinnamoylcocaine, methylecgonine and tropococaine, benzoylecgonine and only 11.1% of the samples did not have alkaloidal impurities as results of the research. Regarding the presence of adulterants in the material analyzed, starch was the most used by cocaine drug dealers in the studied envi-ronment; the use of phenacetin, levamisole and aminopyrine could also be observed.

Human Trafficking: A Guide to Identification and Approach for the Emergency Physician.

Human trafficking is a significant human rights problem that is often associated with psychological and physical violence. There is no demographic that is spared from human trafficking. Traffickers maintain control of victims through physical, sexual, and emotional violence and manipulation. Because victims of trafficking seek medical attention for the medical and psychological consequences of assault and neglected health conditions, emergency clinicians are in a unique position to recognize victims and intervene. Evaluation of possible trafficking victims is challenging because patients who have been exploited rarely self-identify. This article outlines the clinical approach to the identification and treatment of a potential victim of human trafficking in the emergency department. Emergency practitioners should maintain a high index of suspicion when evaluating patients who appear to be at risk for abuse and violence, and assess for specific indicators of trafficking. Potential victims should be evaluated with a multidisciplinary and patient-centered technique. Furthermore, emergency practitioners should be aware of national and local resources to guide the approach to helping identified victims. Having established protocols for victim identification, care, and referrals can greatly facilitate health care providers' assisting this population.

ACTG-HIV symptoms changes in patients switched to RPV/FTC/TDF due to previous intolerance to CART. Interim analysis of the PRO-STR study.

INTRODUCTION: Tolerability and convenience are crucial aspects for the long-term success of combined antiretroviral therapy (cART). The aim of this study was to investigate the impact in routine clinical practice of switching to the single tablet regimen (STR) RPV/FTC/TDF in patients with intolerance to previous cART, in terms of patients' well-being, assessed by several validated measures. METHODS: Prospective, multicenter study. Adult HIV-infected patients with viral load under 1.000 copies/mL while receiving a stable ART for at least the last three months and switched to RPV/FTC/TDF due to intolerance of previous regimen, were included. Analyses were performed by ITT. Presence/magnitude of symptoms (ACTG-HIV Symptom Index), quality of life (EQ-5D, EUROQoL & MOS-HIV), adherence (SMAQ), preference of treatment and perceived ease of medication (ESTAR) through 48 weeks were performed. RESULTS: Interim analysis of 125 patients with 16 weeks of follow up was performed. 100 (80%) were male, mean age 46 years. Mean CD4 at baseline was 629.5±307.29 and 123 (98.4%) had viral load <50 copies/mL; 15% were HCV co-infected. Ninety two (73.6%) patients switched from a NNRTI (84.8% from EFV/FTC/TDF) and 33 (26.4%) from a PI/r. The most frequent reasons for switching were psychiatric disorders (51.2%), CNS adverse events (40.8%), gastrointestinal (19.2%) and metabolic disorders (19.2%). At the time of this analysis (week 16), four patients (3.2%) discontinued treatment: one due to adverse events, two virologic failures and one with no data. A total of 104 patients (83.2%) were virologically suppressed (<50 copies/mL). The average degree of discomfort in the ACTG-HIV Symptom Index significantly decreased from baseline (21±15.55) to week 4 (10.89±12.36) & week 16 (10.81±12.62), p<0.001. In all the patients, quality of life tools showed a significant benefit in well-being of the patients (Table 1). Adherence to therapy significantly and progressively increased (SMAQ) from baseline (54.4%) to week 4 (68%), p<0.001 and to week 16 (72.0%), p<0.001. CONCLUSIONS: Switching to RPV/FTC/TDF from another ARV regimen due to toxicity, significantly improved the quality of life of HIV-infected patients, both in mental and physical components, and improved adherence to therapy while maintaining a good immune and virological response.

Association of ITPA gene polymorphisms and the risk of ribavirin-induced anemia in HIV/hepatitis C virus (HCV)-coinfected patients receiving HCV combination therapy.

Polymorphisms of the ITPA gene have been associated with anemia during combination therapy in hepatitis C virus (HCV)-monoinfected patients. Our aim was to confirm this association in HIV/HCV-coinfected patients. In this prospective, observational study, 73 HIV/HCV-coinfected patients treated with pegylated interferon plus ribavirin (RBV) were enrolled. Two single nucleotide polymorphisms within or adjacent to the ITPA gene (rs1127354 and rs7270101) were genotyped. The associations between the ITPA genotype and anemia or treatment outcome were examined. Fifty-nine patients (80.8%) had CC at rs1127354, whereas 14 (19.2%) had a CA/AA ITPA genotype. Percent decreases from baseline hemoglobin level were significantly greater in patients with the CC genotype than in those with the CA/AA genotype at week 4 (P = 0.0003), week 12 (P < 0.0001), and week 36 (P = 0.0102) but not at the end of treatment. RBV dose reduction was more often needed in patients with the CC genotype than in those with the CA/AA genotype (odds ratio [OR] = 11.81; 95% confidence interval [CI] = 1.45 to 256.17; P = 0.0039), as was erythropoietin therapy (OR = 8.28; 95% CI = 1.04 to 371.12; P = 0.0057). Risk factors independently associated with percent hemoglobin nadir decrease were RBV dose reduction (OR = 11.72; 95% CI = 6.82 to 16.63; P < 0.001), baseline hemoglobin (OR = 1.69; 95% CI = 0.23 to 3.15; P = 0.024), and body mass index (OR = -0.7; 95% CI = -1.43 to 0.03; P = 0.061). ITPA polymorphism was not an independent predictor of sustained virological response. Polymorphisms at rs1127354 in the ITPA gene influence hemoglobin levels during combination HCV therapy and the need for RBV dose reduction and erythropoietin use in HIV/HCV-coinfected patients.

Zinc alpha-2 glycoprotein is implicated in dyslipidaemia in HIV-1-infected patients treated with antiretroviral drugs.

OBJECTIVES: Treated HIV-1-infected patients with lipodystrophy often develop insulin resistance and proatherogenic dyslipidaemia. Zinc alpha-2 glycoprotein (ZAG) is a recently characterized adipokine which has been shown to be involved in the development of obesity and metabolic syndrome in uninfected subjects. We assessed the relationship between circulating ZAG levels and metabolic derangements in HIV-1-infected patients receiving antiretroviral drugs. METHODS: Plasma ZAG levels were assessed in 222 individuals: 166 HIV-1-infected patients treated with antiretroviral drugs (77 with lipodystrophy and 89 without lipodystrophy) and 56 uninfected controls. Plasma ZAG levels were assessed by enzyme-linked immunosorbent assay (ELISA) and were correlated with fat distribution abnormalities and metabolic parameters. RESULTS: HIV-1-infected patients had lower plasma ZAG levels compared with uninfected controls (P < 0.001). No differences were found in ZAG plasma levels according to the presence of lipodystrophy, components of the metabolic syndrome or type of antiretroviral treatment regimen. Circulating ZAG levels were strongly determined by high-density lipoprotein cholesterol (HDLc) in men (B = 0.644; P < 0.001) and showed a positive correlation with total cholesterol (r = 0.312; P < 0.001) and HDLc (r = 0.216; P = 0.005). CONCLUSIONS: HIV-1-infected patients have lower plasma ZAG levels than uninfected controls. In infected patients, plasma ZAG levels are in close relationship with total cholesterol and HDLc.

Relationship between HIV/Highly active antiretroviral therapy (HAART)-associated lipodystrophy syndrome and stavudine-triphosphate intracellular levels in patients with stavudine-based antiretroviral regimens.

BACKGROUND: The link between human immunodeficiency virus/highly active antiretroviral therapy (HAART)-associated lipodystrophy syndrome (HALS) and the use of thymidine analogues has been well established. However, to our knowledge, no relationship has been proven between intracellular levels of stavudine (d4T) and HALS. METHODS: We measured peripheral blood mononuclear cell intracellular levels of d4T-triphosphate (TP) in patients who were receiving d4T as part of their antiretroviral regimens. d4T-TP levels were determined by a validated liquid chromatography-tandem mass spectrometry assay method. The diagnosis of HALS was made in accordance with the criteria of a lipodystrophy severity grading scale. The Student t test, Pearson correlations, 1-way analysis of variance with Bonferroni correction, and stepwise logistic regression were used for statistic analyses. RESULTS: This was a cross-sectional study. There were 33 patients: 17 with HALS and 16 without HALS. The median concentration of d4T-TP for patients with HALS was 20.60 femtomoles (fmol)/1 x 10(6) cells (interquartile range [IQR], 14.90-26.92 fmol/1 x 10(6) cells) and for patients without HALS was 13.85 fmol/1 x 10(6) cells (IQR, 8.65-20.15 fmol/1 x 10(6) cells) (P=.013). The median d4T-TP intracellular level in patients who had developed an AIDS-defining condition was 22.50 fmol/1 x 10(6) cells (IQR, 15.80-27.37 fmol/1 x 10(6) cells) and in those who had not was 14.40 fmol/1 x 10(6) cells (IQR, 10.80-20.40 fmol/1 x 10(6) cells) (P=.037). There were no statistically significant differences in d4T-TP intracellular levels with respect to the presence of metabolic syndrome, the clinical form of HALS (pure lipoatrophic vs mixed), the degree of facial lipoatrophy, the presence of hepatitis C virus infection, and the pair of nucleosides in HAART. d4T-TP levels correlated only with cumulative d4T exposure in time and dose. d4T-TP intracellular levels were independently associated with HALS (odds ratio, 1.58; 95% confidence interval, 1.08-2.32; P=.019). CONCLUSIONS: Intracellular levels of d4T-TP are strongly associated with the development of HALS.