Factors associated with hand hygiene adherence among healthcare workers in Guatemala during the COVID-19 pandemic.

BACKGROUND: Healthcare-associated infections are prevalent in low- and middle-income countries and may be reduced through proper hand hygiene (HH) adherence during patient care. AIM: We produced and distributed alcohol-based hand rub (ABHR) to 19 public primary- and secondary-level healthcare facilities in Quetzaltenango, Guatemala, and carried out HH observations to assess healthcare workers' (HCWs) HH adherence, and to identify factors associated with this practice. HH adherence was defined as washing hands with soap and water or using ABHR. METHODS: Observations were conducted before (2021, baseline) and after (2022, follow-up) ABHR distribution to evaluate the evolution of HH practices over time. Bivariate comparisons and mixed-effects logistic regression models were used to explore associations between HH adherence and the following independent variables: healthcare facility level, type of contact performed, timing of HH performance, occupational category of HCW and materials present (e.g., water, soap, ABHR). FINDINGS: We observed 243 and 300 patient interactions among 67 and 82 HCWs at each time point, respectively. HH adherence was low for both observation periods (40% at baseline and 35% at follow-up). HCWs were more likely to adhere to HH during invasive contacts, after patient contact, and if the HCW was a physician. CONCLUSION: HH adherence varied by scenario, which underscores the importance of addressing multiple determinants of behaviour change to improve adherence. This requires interventions implemented with a multi-modal approach that includes both increasing access to HH materials and infrastructure, as well as HH education and training, monitoring and feedback, reminders, and promoting a HH safety culture.

Nicotine and Alcohol Use as Predictors of Recreational Cannabis Use in Adolescence: A Systematic Review and Narrative Synthesis.

Background: The prevalence of recreational cannabis use among adolescents is a growing public health concern due to its link to short- and long-term adverse effects on adolescents' wellbeing, physical health, mental health, and interpersonal behaviors. Method: Five databases were searched from inception to March 17, 2023, for exposure (nicotine product, alcohol) and outcome (recreational cannabis) in adolescents (persons aged 10-19 years). The studies were screened independently by two reviewers, and the quality of the studies was assessed with Newcastle Ottawa and AXIS tool. PRISMA guidelines were employed in this review. Result: Twenty-one (21) studies involving 2,778,406 adolescents were included in the appraisal and heterogeneity was found among these studies. Ascertainment bias was commonly detected in thirteen (13) of the included studies. Among the substances examined as potential exposures, nicotine-product use emerged as a significant factor associated with future cannabis use among adolescents, particularly in mid-adolescence and in places where recreational cannabis use has been legalized. Conclusion: Current evidence suggests an association between nicotine-product use and subsequent recreational cannabis use among adolescents. However, further research is needed to establish causality between exposure to nicotine substances and the use of recreational cannabis within this age demographic. Additionally, there is a need for the development of prevention programs and targeted policies that continuously inform and update this vulnerable sub-population about the risks associated with cannabis use for leisure.

Informal sale of antibiotics in Guatemalan convenience stores before and after implementation of federal antibiotic dispensing legislation.

BACKGROUND: Convenience stores in Guatemala provide essential consumer goods in communities, but many dispense antibiotics illegally. Federal legislation, passed in August of 2019, requires prescriptions for antibiotic purchase at pharmacies but it is unclear if this legislation is enforced or if it has any impact on unlawful sales of antibiotics. METHODS: To determine if antibiotic availability changed in convenience stores, we carried out a repeated measures study collecting antibiotic availability data before and after implementation of the dispensing regulation. RESULTS: There was no statistical difference in the proportion of convenience stores that sold antibiotics before and after antibiotic regulations [66.6% (295/443) and 66.7% (323/484), respectively, P>0.96], nor in the number of stores selling amoxicillin [55.5% (246/443) and 52.3% (253/484), respectively, P>0.96], but fewer stores (20%) sold tetracycline capsules after regulation was passed (P<0.05). For stores visited both before and after passage of legislation (n=157), 15% stopped selling antibiotics while 25% started selling antibiotics. Antibiotics from convenience stores were reportedly sold for use in people and animals. CONCLUSIONS: Antibiotics remain widely available in convenience stores consistent with no significant change in the informal sector after implementation of prescription requirements for pharmacies. Importantly, effects from regulatory change could have been masked by potential changes in antibiotic use during the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic.

Quality analysis and categorisation of public space.

Public spaces are considered areas that promote users' physical and mental health. The role of these people in public spaces makes it necessary to evaluate such areas. In this study, 12 urban parks on the island of Tenerife were evaluated, combining the assessment of a trained observer and the perception of users, to analyse and categorise the environmental quality of the parks. The findings of this study conclude that users are good evaluators of public spaces; that the Public Space Characteristics Observation Questionnaire (PSCOQ) tool allows the classification of public spaces and that physical order is capable of predicting the environmental quality and the restorative capacity of spaces, as perceived by users. The PSCOQ observation tool makes it possible to detect the strengths and weaknesses of public spaces so they can be improved and adapted to the needs of users.

Poliuria en el adulto. Una aproximación diagnóstica basada en la fisiopatología / Polyuria in adults. A diagnostic approach based on pathophysiology

La poliuria es una condición clínica frecuente caracterizada por un volumen de orina inapropiadamente alto para los niveles de presión arterial y sodio plasmático del paciente (volumen de orina >3L/24h). Desde el punto de vista fisiopatológico se clasifica en 2 tipos: debido a una mayor excreción de solutos (osmolaridad urinaria >300mOsm/L) o debido a una incapacidad de aumentar la concentración de solutos (osmolaridad urinaria <150mOsm/L). En ocasiones pueden coexistir ambos mecanismos (osmolaridad urinaria 150-300mOsm/L). La poliuria supone un reto diagnóstico y su tratamiento correcto exige una evaluación de la historia clínica, la determinación de la osmolaridad urinaria, la estimación del aclaramiento de agua libre, el uso de pruebas de deprivación hídrica en la poliuria acuosa y la medición de electrólitos en sangre y orina en el caso de la poliuria osmótica (AU)

Polyuria is a common clinical condition characterized by a urine output that is inappropriately high (more than 3 liters in 24 hours) for the patient's blood pressure and plasma sodium levels. From a pathophysiological point of view, it is classified into two types: polyuria due to a greater excretion of solutes (urine osmolality >300 mOsm/L) or due to an inability to increase solute concentration (urine osmolality <150 mOsm/L). Sometimes both mechanisms can coexist (urine osmolality 150-300 mOsm/L). Polyuria is a diagnostic challenge and its proper treatment requires an evaluation of the medical record, determination of urine osmolality, estimation of free water clearance, use of water deprivation tests in aqueous polyuria, and measurement of electrolytes in blood and urine in the case of osmotic polyuria (AU)

Polyuria in adults. A diagnostic approach based on pathophysiology.

Polyuria is a common clinical condition characterized by a urine output that is inappropriately high (more than 3 L in 24 h) for the patient's blood pressure and plasma sodium levels. From a pathophysiological point of view, it is classified into two types: polyuria due to a greater excretion of solutes (urine osmolality >300 mOsm/L) or due to an inability to increase solute concentration (urine osmolality <150 mOsm/L). Sometimes both mechanisms can coexist (urine osmolality 150-300 mOsm/L). Polyuria is a diagnostic challenge and its proper treatment requires an evaluation of the medical record, determination of urine osmolality, estimation of free water clearance, use of water deprivation tests in aqueous polyuria, and measurement of electrolytes in blood and urine in the case of osmotic polyuria.

Ex vivo treatment with fucoidan of mononuclear cells from SARS-CoV-2 infected patients.

COVID-19 is a worldwide health emergency, therapy for this disease is based on antiviral drugs and immunomodulators, however, there is no treatment to effectively reduce the COVID-19 mortality rate. Fucoidan is a polysaccharide obtained from marine brown algae, with anti-inflammatory, antiviral, and immune-enhancing properties, thus, fucoidan may be used as an alternative treatment (complementary to prescribed medical therapy) for the recovery of COVID-19.  This work aimed to determine the effects of ex-vivo treatment with fucoidan on cytotoxicity, apoptosis, necrosis, and senescence, besides functional parameters of calcium flux and mitochondrial membrane potential (ΔΨm) on human peripheral blood mononuclear cells isolated from SARS-CoV-2 infected, recovered and healthy subjects. Data suggest that fucoidan does not exert cytotoxicity or senescence, however, it induces the increment of intracellular calcium flux. Additionally, fucoidan promotes recovery of ΔΨm in PBMCs from COVID-19 recovered females. Data suggest that fucoidan could ameliorate the immune response in COVID-19 patients.

Alterations in the non-neuronal cholinergic system induced by in-vitro exposure to diazoxon in spleen mononuclear cells of Nile tilapia (O. niloticus).

Organophosphate pesticides as diazinon disrupt the neuroimmune communication, affecting the innate and adaptive immune response of the exposed organisms. Since the target molecule of diazinon is typically the acetylcholinesterase enzyme (AChE), the existence of a non-neuronal cholinergic system in leukocytes makes them susceptible to alterations by diazinon. Therefore, the aim of this work was to evaluate the activity of AChE, acetylcholine (ACh) concentration, and the expression of nicotinic ACh receptors (nAChR) and muscarinic ACh receptors (mAChR) in spleen mononuclear cells (SMNC) of Nile tilapia (O. niloticus) exposed in vitro to diazoxon, a diazinon metabolite. SMNC were exposed in-vitro to 1 nM, 1 µM, and 10 µM diazoxon for 24 h. The enzyme activity of AChE was then evaluated by spectrophotometry, followed by ACh quantification by ultra-performance liquid chromatography. Finally, mAChR and nAChR expression was evaluated by RT-qPCR. The results indicate that AChE levels are significantly inhibited at 1 and 10 µM diazoxon, while the relative expression of (M3, M4, and M5) mAChR and (ß2) nAChR is reduced significantly as compared against SMNC not exposed to diazoxon. However, ACh levels show no significant difference with respect to the control group. The data indicate that diazoxon directly alters elements in the cholinergic system of SMNC by AChE inhibition or indirectly through the interaction with AChR, which is likely related to the immunotoxic properties of diazinon and its metabolites.

In-vitro effect of diazoxon, a metabolite of diazinon, on proliferation, signal transduction, and death induction in mononuclear cells of Nile tilapia fish (Oreochromis niloticus).

The immune response of teleosts (bonefish) is altered by diazinon (DZN), an organophosphate pesticide. It has been suggested that such alteration is due to the extraneuronal cholinergic system in fish leukocytes that renders these cells a target of pesticides. Diazoxon (DZO), the oxon metabolite of DZN, has been attributed immunotoxic effects. Still, to date there are no reports on the effects of DZO upon parameters involved in the signaling cascade of immune response cells. Therefore, this work evaluated the effect of DZO on key parameters of cell signaling (intracellular Ca2+ flux, ERK 1/2 phosphorylation), cell proliferation, and antiproliferative processes (apoptosis, senescence, mitochondrial membrane potential) in spleen mononuclear cells of Nile tilapia fish. The results obtained show that DZO does not affect cell proliferation but causes a lack of response to stimulation with PMA and ionomycin to release intracellular calcium. In addition, it inhibits ERK 1/2 phosphorylation and causes loss of mitochondrial membrane potential, apoptosis, and senescence. These results suggest that the lack of cell response to release intracytoplasmic Ca2+ inhibits ERK which disrupts the mitochondrial membrane potential, leading to cell apoptosis and senescence. These findings prove that DZO significantly affects key parameters involved in the survival of immune response cells.

Effect of diazinon, an organophosphate pesticide, on signal transduction and death induction in mononuclear cells of Nile tilapia fish (Oreochromis niloticus).

Diazinon (DZN) is an organophosphate pesticide characterized by inhibiting the enzyme acetylcholinesterase (AChE) (E.C. 3.1.1.7), affecting the nervous system. There is currently enough evidence proving this pesticide also affects the immune response; however, the immunotoxicity mechanisms through which these substances exerts toxic effects remain unclear. For that reason, this work evaluated the effect of diazinon on the intracellular calcium flux, ERK1/2 phosphorylation (pERK1/2), apoptosis, senescence, and mitochondrial membrane potential (ΔΨm) in spleen mononuclear cells (SMNC) of Nile tilapia, a teleost fish of commercial and ecological relevance. The results obtained indicate that diazinon causes significant damage in all evaluated parameters, which play an essential role in intracytoplasmic signaling of immune cells, suggesting these signal pathways could be related with the immunotoxicity mechanism of these type of pesticides.

Muscarinic acetylcholine receptor expression in brain and immune cells of Oreochromis niloticus.

Nervous and immune systems maintain a bidirectional communication, expressing receptors for neurotransmitters and cytokines. Despite being well established in mammals, this has been poorly described in lower vertebrates as fishes. Experimental evidence shows that the neurotransmitter acetylcholine (ACh) regulates the immune response. In this research, we evaluated mRNA levels of muscarinic acetylcholine receptor (mAChR) in spleen mononuclear cells of Nile tilapia (Oreochromis niloticus) and compared the expression levels of immune cells with the brain. The mAChR subtypes (M2-M5A) were detected in both tissues, but mAChRs mRNA levels were higher in immune cells. This data have a potential use in biomedical and comparative immunology fields.

Phagocytosis and ROS production as biomarkers in Nile tilapia (Oreochromis niloticus) leukocytes by exposure to organophosphorus pesticides.

Organophosphorus pesticides (OPs) are broad-spectrum insecticides. One of the commonly used OPs is diazinon (DZN). The aim of this study was to evaluate the immunotoxic effect of DZN on phagocytic parameters of blood leukocytes using the teleost fish Oreochromis niloticus as a study model. For this purpose, fish were exposed in vivo to 0.97, 1.95 and 3.97 mg/L of DZN for 6 and 24 h. Our results indicated that phagocytic active cells decreased in fish exposed in vivo to 0.97 and 1.95 mg/L of DZN for 6 and 24 h. Regarding ROS production, H2O2 and O2- levels were higher on fish exposed to 1.95 mg/L for 6 and 24 h, while H2O2 production increased at 0.97 mg/L for 24 h. From this we can conclude that phagocytic parameters are sensitive to assess the effect of acute intoxication with organophosphorus pesticides on Nile tilapia.

Behavioral and subjective health changes in US and Mexico border residing participants in two promotora-led chronic disease preventive interventions.

Chronic diseases are the primary health burden among Mexican-origin populations and health promotion efforts have not been able to change negative population trends. This research presents behavioral and subjective health impacts of two related community health worker (CHW) interventions conducted in the US-Mexico border region. Pasos Adelante (United States) and Meta Salud (Mexico) are 12-13 week CHW-led preventive interventions implemented with Mexico-origin adults. Curricula include active learning modules to promote healthy dietary changes and increasing physical activity; they also incorporate strategies to promote social support, empowerment and group exercise components responsive to their communities. Questionnaire data at baseline (N = 347 for Pasos; 171 for Meta Salud), program completion and 3-month follow-up were analyzed. Results showed statistically significant improvements in multiple reported dietary, physical activity and subjective health indicators. Furthermore, at follow-up across both cohorts there were ≥10% improvements in participants' meeting recommended physical activity guidelines, consumption of whole milk, days of poor mental health and self-rated health. While this study identifies some robust health improvements and contributes to the evidence base for these interventions current dissemination, the lack of change observed for some targeted behaviors (e.g. time sitting) suggests they may have stronger overall impacts with curricula refinement.

Human Neutrophil Defensin-1, -3, and -4 Are Elevated in Nasal Aspirates from Children with Naturally Occurring Adenovirus Infection.

Background: Adenoviruses are highly contagious pathogens which cause respiratory disease particularly in children; they may induce severe disease in infants. Human neutrophil peptides (HNPs) have been found to exhibit antiadenoviral activity. Thus, we have investigated HNPs in nasal aspirates (NAs) of children suffering from adenoviral common cold. Objective: To investigate the release of HNP-1-4 in adenovirus infection and the relationship with self-limiting upper respiratory tract infections. Methods: Nasal aspirate samples (n=14) were obtained from children (aged 6-12 years) infected with adenovirus between June 2012 and December 2015. Control samples were taken 4 weeks after infection when the children were asymptomatic. Levels of HNPs were measured using an enzyme-linked immunosorbent assay (ELISA). Results: There were increased levels of HNP-1, -3, and -4, but not HNP-2, in nasal aspirates (NAs) during adenovirus infections compared to healthy specimens (p ≤ 0.01). Moreover, there was also increase in the neutrophil count, which is a known cell source of HNPs. Conclusion: Our finding supports the involvement of HNP-1, -3, and -4 in naturally occurring cold in children infected with adenovirus. Because of their known antiviral properties, it is tempting to hypothesize that HNPs might play a protective role in adenovirus-induced respiratory disease; however, this remains to be shown.

Seguridad de las fluoroquinolonas: riesgos habitualmente olvidados para el clínico / Safety of fluoroquinolones: risks usually forgotten for the clinician

Resumen Las quinolonas constituyen una familia de antimicrobianos de amplio uso y si bien son consideradas segura para los pacientes, el conocimiento del perfil de seguridad es necesario para que los profesionales estén alertas a lo que deben vigilar. Sobre el sistema músculo-esquelético, las quinolonas tienen el potencial de dañar cartílagos, provocando incluso muy excepcionalmente rotura de tendón. A nivel endocrino se ha observado hipoglicemia/hiperglicemia, por lo que en pacientes diabéticos se recomienda el control cuidadoso de la glicemia. Las reacciones adversas cardiovasculares son poco frecuentes, pero pueden ir desde alteraciones del ECG como prolongación del QT sin traducción clínica a graves arritmias que pueden ser de riesgo vital. En el sistema nervioso, destaca la aparición de alteraciones del sistema nervioso central y la neuropatía periférica. Durante la evaluación de la seguridad de las quinolonas es importante considerar las potenciales interacciones con otros medicamentos. En niños se prefiere no usar las fluoroquinolonas debido al potencial riesgo de daño a los cartílagos de crecimiento, efectos que no parecen ser tan dramáticos a la luz de la evidencia actual. A pesar del optimismo se debe evaluar la seguridad del tratamiento de estos antimicrobianos en todo paciente pediátrico.

Quinolones are a group of widely used antimicrobials. Although they are considered safe for patients, knowledge of the safety profile is necessary so that professionals become aware of what is necessary to monitor. At the musculoskeletal level, quinolones have the potential to damage cartilage, causing even tendon rupture in infrequent cases. Hypoglycemia / hyperglycemia has been observed at the endocrine level, thus, careful monitoring of glycemia in patients with quinolone is recommended in diabetic patients. At the cardiovascular level, arrhythmias induced by these antimicrobials are rare but severe. At the level of the nervous system, the appearance of alterations of the central nervous system and the peripheral neuropathy are emphasized. When assessing the safety of quinolones, it is important to consider potential interactions with other substances (medical products). In children it is preferred not to use fluoroquinolones because of the potential risk of cartilage damage and growth, effects that do not seem to be so dramatic in the face of new evidence. Despite optimism, the safety of the treatment of these antimicrobials should be evaluated in every pediatric patient.

[Safety of fluoroquinolones: risks usually forgotten for the clinician]. / Seguridad de las fluoroquinolonas: riesgos habitualmente olvidados para el clínico.

Quinolones are a group of widely used antimicrobials. Although they are considered safe for patients, knowledge of the safety profile is necessary so that professionals become aware of what is necessary to monitor. At the musculoskeletal level, quinolones have the potential to damage cartilage, causing even tendon rupture in infrequent cases. Hypoglycemia / hyperglycemia has been observed at the endocrine level, thus, careful monitoring of glycemia in patients with quinolone is recommended in diabetic patients. At the cardiovascular level, arrhythmias induced by these antimicrobials are rare but severe. At the level of the nervous system, the appearance of alterations of the central nervous system and the peripheral neuropathy are emphasized. When assessing the safety of quinolones, it is important to consider potential interactions with other substances (medical products). In children it is preferred not to use fluoroquinolones because of the potential risk of cartilage damage and growth, effects that do not seem to be so dramatic in the face of new evidence. Despite optimism, the safety of the treatment of these antimicrobials should be evaluated in every pediatric patient.

Periparturient characteristics of mares and their foals on a New Zealand Thoroughbred stud farm.

AIMS: To describe selected periparturient variables in a sample of Thoroughbred mares and their foals on a commercial stud farm in New Zealand. METHODS: Data were collected for 969 foaling records, from 592 mares, by foaling attendants from one Thoroughbred stud farm in the Waikato region of New Zealand for the breeding seasons 2008-2013, inclusive, and collated retrospectively. The associations between mare- and foal-level variables and gestation length, time of birth (expressed as the number of hours after midday), fetal membrane retention time, time for the foal to stand and suckle after birth, and foal mortality were quantified using linear and logistic regression models. RESULTS: Mean gestation length for mares in this study was 350 (min 296, max 429) days, and was shorter for filly foals (348 (min 296, max 429) days) compared with colt foals (350 (min 310, max 404) days) (p=0.001). Overall, 517/968 (53%) foalings occurred between 19:00 and 01:00 and 212/968 (22%) foalings occurred during daylight. Overall, 815/855 (95%) expelled their fetal membranes within 4 hours of parturition. The mean interval from birth to standing and to suckling was shorter (p<0.001) for filly foals than colts by 13 (95% CI=9-17) and 17 (95% CI=8-26) minutes, respectively. Dystocia was reported for 81/968 (8.4%) foalings with relative fetal oversize being the most common cause (36/81 (44%) cases). Perinatal foal death was recorded for 26/966 (2.7%) foalings. The odds of foal mortality decreased with increasing length of gestation (p=0.027), and were greater for colt than filly foals (p=0.042) and when dystocia was reported (p<0.001). CONCLUSIONS: Gestation length was influenced by the sex of the foal, as was the time taken for the foal to stand and suckle after birth. One fifth of mares foaled during daylight hours. The majority of mares in this study population expelled their fetal membranes within 4 hours of foaling. CLINICAL RELEVANCE: Accurate measures for periparturient behaviour can be important in the management of mares and newborn foals. Clinically relevant differences appear to exist between mares and foals in New Zealand and those in the Northern Hemisphere for some key parameters, likely as a result of differences in management and environment. The results of this study suggest that mares should be considered to have retained their membranes if not passed within 4 hours of parturition.

Prenatal exposure to cannabis and maternal and child health outcomes: a systematic review and meta-analysis.

OBJECTIVE: To assess the effects of use of cannabis during pregnancy on maternal and fetal outcomes. DATA SOURCES: 7 electronic databases were searched from inception to 1 April 2014. Studies that investigated the effects of use of cannabis during pregnancy on maternal and fetal outcomes were included. STUDY SELECTION: Case-control studies, cross-sectional and cohort studies were included. DATA EXTRACTION AND SYNTHESIS: Data synthesis was undertaken via systematic review and meta-analysis of available evidence. All review stages were conducted independently by 2 reviewers. MAIN OUTCOMES AND MEASURES: Maternal, fetal and neonatal outcomes up to 6 weeks postpartum after exposure to cannabis. Meta-analyses were conducted on variables that had 3 or more studies that measured an outcome in a consistent manner. Outcomes for which meta-analyses were conducted included: anaemia, birth weight, low birth weight, neonatal length, placement in the neonatal intensive care unit, gestational age, head circumference and preterm birth. RESULTS: 24 studies were included in the review. Results of the meta-analysis demonstrated that women who used cannabis during pregnancy had an increase in the odds of anaemia (pooled OR (pOR)=1.36: 95% CI 1.10 to 1.69) compared with women who did not use cannabis during pregnancy. Infants exposed to cannabis in utero had a decrease in birth weight (low birth weight pOR=1.77: 95% CI 1.04 to 3.01; pooled mean difference (pMD) for birth weight=109.42 g: 38.72 to 180.12) compared with infants whose mothers did not use cannabis during pregnancy. Infants exposed to cannabis in utero were also more likely to need placement in the neonatal intensive care unit compared with infants whose mothers did not use cannabis during pregnancy (pOR=2.02: 1.27 to 3.21). CONCLUSIONS AND RELEVANCE: Use of cannabis during pregnancy may increase adverse outcomes for women and their neonates. As use of cannabis gains social acceptance, pregnant women and their medical providers could benefit from health education on potential adverse effects of use of cannabis during pregnancy.

Speciated High-Density Lipoprotein Biogenesis and Functionality.

Plasma high-density lipoprotein cholesterol (HDL-C) concentration is a negative risk factor for atherosclerotic cardiovascular disease (CVD). Despite this, most attempts to raise plasma HDL-C concentrations in a cardioprotective way have failed. Recently, hypotheses about the atheroprotective effects of HDL have shifted away from quantity to quality, mostly HDL function in reverse cholesterol transport. Plasma HDL from CVD patients is a poorer acceptor of cellular cholesterol than plasma from healthy controls, independent of plasma HDL-C concentrations. The function of HDL is likely determined by two other factors, stability and composition. The kinetic instability of HDL, which varies according to subclass, is a likely determinant of its reactivity in response to many HDL-modifying activities. HDL composition is also heterogeneous and variable; all HDL particles contain apo AI but only about two-thirds contain apo AII. This occurs despite the fact that apo AI and apo AII are hepatically secreted on separate HDL that later fuse in plasma. HDL also contains traces of other proteins, some of which have not yet been associated with HDL function. One minor HDL species are those that are secreted with intact signal peptides, which enhances their binding to HDL; these HDL have special properties that are independent of cholesterol transport. Here, we review and provide a perspective about what is currently known about speciated HDL biogenesis in the context of health and disease.