Special Issue "Application Progress of Liposomes in Drug Development".

The second edition of the Special Issue entitled the "Application Progress of Liposomes in Drug Development" featured contributions predominantly focused on leveraging liposomes as enhancers and carriers in drug delivery in the context of cancer treatment, although this was not the initial intent of this Special Issue [...].

Liposomes: The Brave Old World.

Liposomes have been known of for about 60 years, since they were discovered by A [...].

Changes in prevalence and the cascade of care for type 2 diabetes over ten years (2005-2015): results of two nationally representative surveys in Mozambique.

BACKGROUND: Sub-Saharan Africa is predicted to have the steepest increase in the prevalence of diabetes in the next 25 years. The latest Mozambican population-based STEPS survey (STEPS 2005) estimated a 2.9% prevalence of diabetes in the adult population aged 25-64 years. We aimed to assess the change in prevalence, awareness, and management of diabetes in the national STEPS survey from 2014/2015 compared to 2005. METHODS: We conducted an observational, quantitative, cross-sectional study following the WHO STEPS surveillance methodology in urban and rural settings, targeting the adult population of Mozambique in 2015. We collected sociodemographic data, anthropometric, and 12 hour fasting glucose blood samples in a sample of 1321 adults. The analysis consisted of descriptive measures of the prevalence of impaired fasting glucose (IFG), diabetes and related risk factors by age group, sex, and urban/rural residence and compared the findings to those of the 2005 survey results. RESULTS: The prevalence of IFG and diabetes was 4.8% (95CI: 3.6-6.3) and 7.4% (95CI: 5.5-10.0), respectively. These prevalence of IFG and diabetes did not differ significantly between women and men. The prevalence of diabetes in participants classified with overweight/obesity [10.6% (95CI: 7.5-14.6)] and with central obesity (waist hip ratio) [11.0% (95CI: 7.4-16.1)] was almost double the prevalence of their leaner counterparts, [6.3% (95CI, 4.0-9.9)] and [5.2% (95CI: 3.2-8.6)], respectively. Diabetes prevalence increased with age. There were 50% more people with diabetes in urban areas than in rural. Only 10% of people with diabetes were aware of their disease, and only 44% of those taking oral glucose-lowering drugs. The prevalence of IFG over time [2.0% (95CI: 1.1-3.5) vs 4.8% (95CI: 3.6-6.3)] and diabetes [2.9% (95CI: 2.0-4.2) vs 7.4% (95CI: 5.5-10.0)] were more than twofold higher in 2014/2015 than in 2005. However, awareness of disease and being on medication decreased by 3% and by 50%, respectively. Though this was not statistically significant. CONCLUSIONS: While the prevalence of diabetes in Mozambique has increased from 2005 to 2015, awareness and medication use have declined considerably. There is an urgent need to improve the capacity of primary health care and communities to detect, manage and prevent the occurrence of NCDs and their risk factors.

HCC Detection on Surveillance US: Comparing Focused Liver Protocol Using US LI-RADS Technical Guidelines to a General Complete Abdominal US Protocol.

OBJECTIVE: Focused US examinations of the liver in the routine hepatocellular carcinoma (HCC) screening reduce the time spent on evaluating other structures deemed irrelevant to the clinical setting. It is still unknown, however, if such a strategy may additionally improve the frequency of nodules detection. We aimed to assess the impact of an HCC surveillance program in high-risk patients by means of targeted liver US following LI-RADS technical guidelines in comparison to a complete upper abdominal scan. METHODS: In this IRB-approved, single-center, prospective study, patients at high-risk for HCC enrolled from 06/2016 to 09/2019 were randomly assigned to 1 of the 2 institutional protocols: Group A (targeted liver US) or Group B (complete upper abdominal scan). Twenty examiners with similar experience in abdominal US were randomly assigned to perform the examinations exclusively in 1 of the groups (10 in each group). Frequency of hepatic nodules between groups was compared by using Fisher's exact test. RESULTS: Four hundred and sixty-five patients were enrolled, with no significant differences in both groups regarding sex, age, etiology of liver disease, MELD scores, and alpha-fetoprotein levels. A significantly higher frequency of nodules detection was found in Group A (230 patients; 23 nodules detected; 10% of the sample) in comparison to Group B (235 patients; 3 nodules; 1.3% of the sample) (p <.001). Five patients in Group A and 1 in Group B were positive for HCC after full diagnostic work-up. CONCLUSION: Adopting an HCC screening program based on targeted liver US improved the detection of hepatic nodules among high-risk individuals.

Elastic and Ultradeformable Liposomes for Transdermal Delivery of Active Pharmaceutical Ingredients (APIs).

Administration of active pharmaceutical ingredients (APIs) through the skin, by means of topical drug delivery systems, is an advanced therapeutic approach. As the skin is the largest organ of the human body, primarily acting as a natural protective barrier against permeation of xenobiotics, specific strategies to overcome this barrier are needed. Liposomes are nanometric-sized delivery systems composed of phospholipids, which are key components of cell membranes, making liposomes well tolerated and devoid of toxicity. As their lipid compositions are similar to those of the skin, liposomes are used as topical, dermal, and transdermal delivery systems. However, permeation of the first generation of liposomes through the skin posed some limitations; thus, a second generation of liposomes has emerged, overcoming permeability problems. Various mechanisms of permeation/penetration of elastic/ultra-deformable liposomes into the skin have been proposed; however, debate continues on their extent/mechanisms of permeation/penetration. In vivo bioavailability of an API administered in the form of ultra-deformable liposomes is similar to the bioavailability achieved when the same API is administered in the form of a solution by subcutaneous or epi-cutaneous injection, which demonstrates their applicability in transdermal drug delivery.

Prevalence of overweight and obesity in Mozambique in 2005 and 2015.

OBJECTIVE: The ongoing demographic, nutritional and epidemiological transitions in sub-Saharan Africa highlight the importance of monitoring overweight and obesity. We aimed to assess the prevalence of overweight and obesity in Mozambique in 2014/2015 and compare the estimates with those obtained in 2005. DESIGN: Cross-sectional study conducted in 2014/2015, following the WHO Stepwise Approach to Chronic Disease Risk Factor Surveillance (STEPS). Prevalence estimates with 95 % CI were computed for different categories of BMI and abdominal obesity, along with age-, education- and income-adjusted OR. The age-standardized prevalence in the age group 25-64 years was compared with results from a STEPS survey conducted in 2005. SETTING: Mozambique. PARTICIPANTS: Representative sample of the population aged 18-64 years (n 2595). RESULTS: Between 2005 and 2014/2015, the prevalence of overweight and obesity increased from 18·3 to 30·5 % (P < 0·001) in women and from 11·7 to 18·2 % (P < 0·001) in men. Abdominal obesity increased among women (from 9·4 to 20·4 %, P < 0·001), but there was no significant difference among men (1·5 v. 2·1 %, P = 0·395). In 2014/2015, the prevalence of overweight and obesity was more than twofold higher in urban areas and in women; in the age group 18-24 years, it was highest in urban women and lowest in rural men. CONCLUSIONS: In Mozambique, there was a steep increase in the prevalence of overweight and obesity among adults between 2005 and 2014/2015. Overweight and obesity are more prevalent in urban areas and among women, already affecting one in five urban women aged 18-24 years.

Amyloid-ß effects on synapses and memory require AMPA receptor subunit GluA3.

Amyloid-ß (Aß) is a prime suspect for causing cognitive deficits during the early phases of Alzheimer's disease (AD). Experiments in AD mouse models have shown that soluble oligomeric clusters of Aß degrade synapses and impair memory formation. We show that all Aß-driven effects measured in these mice depend on AMPA receptor (AMPAR) subunit GluA3. Hippocampal neurons that lack GluA3 were resistant against Aß-mediated synaptic depression and spine loss. In addition, Aß oligomers blocked long-term synaptic potentiation only in neurons that expressed GluA3. Furthermore, although Aß-overproducing mice showed significant memory impairment, memories in GluA3-deficient congenics remained unaffected. These experiments indicate that the presence of GluA3-containing AMPARs is critical for Aß-mediated synaptic and cognitive deficits.

Practical Considerations of Real Life of Hepatocellular Carcinoma in a Tertiary Center of Brazil.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common malignancy that develops in cirrhotic livers. Its clinical and epidemiological characteristics and mortality rates vary according to geographical region. The objective of this study was to evaluate the clinical profile, epidemiological characteristics, laboratory parameters, treatment and survival of patients with HCC. MATERIAL AND METHODS: Patients with HCC seen between 2000 and 2012 were studied. The Kaplan-Meier method was used for survival analysis according to variables in question. RESULTS: The study included 247 patients with a mean age of 60 ± 10 years. There was a predominance of males (74%). The main etiologies of HCC were HCV infection (55%), excessive alcohol consumption (12%), and HBV infection (8%). Liver cirrhosis was present in 92% of cases. The mean tumor number and diameter were 2 and 5 cm, respectively. Patients meeting the Milan criteria corresponded to 43% of the sample. Liver transplantation was performed in 22.4% of patients of the Milan subset and in 10% of the whole sample. The overall mean survival was 60 months, with a 1-, 3- and 5-year survival probability of 74%, 40% and 29%, respectively. Lower survival was observed among patients with alcoholic etiology. Survival was higher among patients submitted to liver transplantation (P &lt; 0.001), TACE (P &lt; 0.001), or any kind of treatment (P &lt; 0.001). However, no difference was found for surgical resection (P = 0.1) or sorafenib (P = 0.1). CONCLUSION: Patients with HCC were mainly older men diagnosed at an advanced stage. Treatment was associated with better overall survival, but few patients survived to be treated.

Model-based patterns of cardiovascular risk factors in Mozambique.

BACKGROUND: Risk factors for cardiovascular diseases tend to cluster, although evidence from settings under epidemiological transition is scarce. AIM: To identify patterns of clustering of cardiovascular risk factors and to quantify their association with sociodemographic characteristics, in Mozambique. SUBJECTS AND METHODS: A national representative sample (n = 3323) of subjects aged 25-64 years was evaluated in 2005, using the World Health Organization Stepwise Approach to Chronic Disease Risk Factor Surveillance (STEPS). Patterns of joint exposure to high blood pressure, high fasting blood glucose, high body mass index, smoking, excessive alcohol consumption, low fruit/vegetables intake and insufficient physical activity were identified through latent class analysis. RESULTS: Three patterns were identified among women: (1) "healthier", lower frequency of most risk factors (53.0%); (2) "hypertension-overweight" (21.1%), more frequent among older and urban subjects; and (3) "hypertension-smoking-alcohol" (25.9%), whose frequency increased with age and decreased with education. In men, two clusters were identified: (1) "hypertension-overweight" (30.1%); and (2) "smoking" (69.9%). The frequency of the latter pattern was higher in urban areas and increased with age and education. CONCLUSION: Hypertension, overweight/obesity, smoking and excessive alcohol intake defined the main clusters of cardiovascular risk factors. This should be considered when planning prevention and control strategies for cardiovascular diseases in Mozambique.

Prevention of childhood obesity: a review of the current guidelines and supporting evidence.

BACKGROUND: Childhood obesity is considered by many one of the biggest public health issues facing our country. In the U.S. almost one in three children are overweight and one in five are obese. This article aims to outline the current childhood obesity prevention measures as well as discuss programs that have had success in reducing childhood overweight and obesity. METHODS: Recent literature on prevention of childhood obesity was reviewed. There was a focus on systematic reviews, random controlled trials and well-designed observational studies. RESULTS: Evidenced-based prevention of childhood obesity demonstrates that there is a benefit to programs that focus on a collaboration of community/school, primary health care, and home/family based interventions that involve both a physical activity and dietary component. Successful programs have more efficacy if they are longer in duration and initiated for children in middle school or younger. DISCUSSION: The most recent recommendations regarding prevention of childhood obesity focus on increased exercise and improved diet to prevent childhood obesity. Despite these clear recommendations and general consensus for them, childhood obesity continues to increase. The evidence supports a collaborative effort with multiple stakeholders to reverse the trend in childhood obesity.

Mechanical ventilation and mobilization: comparison between genders.

[Purpose] To investigate the impact of gender on mobilization and mechanical ventilation in hospitalized patients in an intensive care unit. [Subjects and Methods] A retrospective cross-sectional study was conducted of the medical records of 105 patients admitted to a general intensive care unit. The length of mechanical ventilation, length of intensive care unit stay, weaning, time to sitting out of bed, time to performing active exercises, and withdrawal of sedation exercises were evaluated in addition to the characteristics of individuals, reasons for admission and risk scores. [Results] Women had significantly lower values APACHE II scores, duration of mechanical ventilation, time to withdrawal of sedation and time to onset of active exercises. [Conclusion] Women have a better functional response when admitted to the intensive care unit, spending less time ventilated and performing active exercises earlier.

Spectrum of pediatric cancers in Mozambique: an analysis of hospital and population-based data.

The existing data provide little detail about the epidemiology of pediatric cancers in Mozambique. We aimed at characterizing the spectrum of pediatric cancers (0-14 years) diagnosed in Mozambique in two different calendar periods. Data were obtained from the Pathology Department of the Maputo Central Hospital (DP-HCM) (1999-2000 and 2009-2010), which receives virtually all samples for histopathological diagnosis in Maputo, with the exception of leukemia, and from the population-based Cancer Registry of Beira (2009-2010). In 1999-2000, the DP-HCM diagnosed 61 cancers. Burkitt lymphoma, malignant bone tumors, and rhabdomyosarcomas accounted for 24.6%, 11.5%, and 9.8% of all cases, respectively. In 2009-2010, the number of cancers increased to 150, reflecting a two- to threefold increase in the proportion of Kaposi sarcomas, non-Hodgkin lymphomas, nephroblastomas, and neuroblastomas. In 2009-2010, the Cancer Registry of Beira registered 34 cases, corresponding to an incidence rate of 9.7/100,000 inhabitants in this age group; Kaposi sarcomas, lymphomas, retinoblastomas, and nephroblastomas accounted for 29.4%, 23.5%, 8.8%, and 8.8% of all cases, respectively. These data show that pediatric cancers account for an appreciable burden in Mozambique, probably reflecting a high frequency of HIV-associated cancers and improved access to diagnosis, and highlight the potential for improving surveillance in this low resource setting.

Trace element compositional changes in human milk during the first four months of lactation.

The aims of this paper were to evaluate changes in specific oligoelements in human milk during the first four months of lactation and to correlate such changes with total antioxidant status (TAS) and other parameters, such as the mother's age, primipara versus multipara, and supplement intake. Milk samples were collected from 31 lactating women following 1, 4, 8, 12 and 16 weeks after birth. Trace levels of 13 elements were measured by inductively coupled plasma-mass spectrometry (ICP-MS). The results obtained for the oligoelements exhibited a decrease in concentration from 7 days to 4 months of breast-feeding, with exceptions. Correlations were found between TAS and Co, V, Rb and Tl. Between primipara and multipara, differences were found for Ni and Rb. Regarding the mother's age, correlation was found for Rb and Ba (increased for mothers older than 30 years). Increased amounts of Rb, Mo and Tl at any lactation period appeared in women who took supplements.

The effect of season and temperature variation on hospital admissions for incident stroke events in Maputo, Mozambique.

BACKGROUND: Identifying locale-specific patterns regarding the variation in stroke incidence throughout the year and with atmospheric temperature may be useful to the organization of stroke care, especially in low-resource settings. GOAL: We aimed to describe the variation in the incidence of stroke hospitalizations across seasons and with short-term temperature variation, in Maputo, Mozambique. METHODS: Between August 1, 2005, and July 31, 2006, we identified 651 stroke events in Maputo dwellers, according to the World Health Organization's STEPwise approach. The day of symptom onset was defined as the index date. We computed crude and adjusted (humidity, precipitation and temperature) incidence rate ratios (IRRs) and 95% confidence intervals (CIs) with Poisson regression. RESULTS: Stroke incidence did not vary significantly with season (dry versus wet: crude IRR = .98, 95% CI: .84-1.15), atmospheric temperature at the index date, or average atmospheric temperature in the preceding 2 weeks. The incidence rates of stroke were approximately 30% higher when in the previous 10 days there was a decline in the minimum temperature greater than or equal to 3 °C between any 2 consecutive days (variation in minimum temperature -5.1 to -3.0 versus -2.3 to -.4, adjusted IRR = 1.31, 95% CI: 1.09-1.57). No significant associations were observed according to the variation in maximum temperatures. CONCLUSIONS: Sudden declines in the minimum temperatures were associated with a higher incidence of stroke hospitalizations in Maputo. This provides important information for prediction of periods of higher hospital affluence because of stroke and to understand the mechanisms underlying the triggering of a stroke event.

Tobacco consumption in Mozambique in 2005 and 2015.

INTRODUCTION: The burden related to smoking exposure is growing in many low-income settings. We aimed to quantify the use of smoked and smokeless tobacco in Mozambique in 2014/2015, and to compare the estimates with those obtained in 2005. METHODS: A cross sectional study was conducted in 2014/2015 on a representative sample of the Mozambican population aged 15 to 64 years, following the World Health Organization Stepwise Approach to Chronic Disease Risk Factor Surveillance (STEPS). Prevalence estimates with 95% confidence intervals were computed for different categories of tobacco consumption. The age-standardised prevalence in the age-group 25-64 years was compared with results from a STEPS survey conducted in 2005. RESULTS: Between 2005 and 2014/2015, the prevalence of daily smoking decreased from 9.1% to 3.4% (p < 0.05) in women and from 33.6% to 27.3% (p < 0.05) in men. There was a significant decrease in the daily consumption of hand-rolled cigarettes among women (from 3.1% to 1.4%, p < 0.05). Among men, there was a decrease in the prevalence of daily consumption of smokeless tobacco (from 3.5% to 1.0%, p < 0.05). In 2014/2015, both manufactured and hand-rolled cigarette consumption were more prevalent among men, while the use of smokeless tobacco was more common among women; the consumption of both hand-rolled cigarettes and smokeless tobacco were more prevalent in rural settings. DISCUSSION AND CONCLUSIONS: In Mozambique, there was a decrease in the prevalence of daily smokers in both genders and of daily consumption of smokeless tobacco among men between 2005 and 2014/2015. Efforts are needed to maintain the positive trends.

Tobacco consumption in Mozambique: use of distinct types of tobacco across urban and rural settings.

INTRODUCTION: Monitoring tobacco consumption patterns is essential to define and evaluate strategies to control the tobacco epidemic. We aimed to quantify the use of smoked (manufactured/hand-rolled cigarettes) and smokeless (snuff/chew) tobacco, according to sociodemographic characteristics, in adult Mozambicans. METHODS: A national representative sample (n = 3,323) of subjects aged 25-64 years was evaluated in 2005 following the World Health Organization Stepwise Approach to Chronic Disease Risk Factor Surveillance (STEPS), which included the assessment of tobacco consumption with the quantification of each type of tobacco used daily. We computed prevalences, and age- and education-adjusted prevalence ratios (PRs), with 95% CIs. RESULTS: Daily smoking was reported by 9.1% (95% CI = 5.0-13.1) of women (manufactured, 3.4%; hand-rolled, 5.6%) and 33.6% (95% CI = 29.3-38.0) of men (manufactured, 18.7%; hand-rolled, 14.8%). Daily manufactured cigarette smoking was significantly more frequent in men (urban: PR = 14.62, 95% CI = 7.59-28.55; rural: PR = 4.32, 95% CI = 2.42-7.71). Daily hand-rolled cigarette smoking was three- to fourfold more frequent among men and nearly 80% less frequent in urban areas, regardless of sex. The prevalence of daily smokeless tobacco use was 7.4% (95% CI = 4.6-10.2) in women (chew, 6.4%; snuff, 1.0%) and 3.4% (95% CI = 1.7-5.2) in men (chew, 1.6%; snuff, 1.8%). Daily smokeless tobacco consumption was significantly less frequent in urban areas only among men (PR = 0.05, 95% CI = 0.01-0.33). CONCLUSIONS: Despite the relatively low levels of manufactured cigarette smoking, traditional forms of tobacco consumption are frequent, especially among women and in rural settings, showing the need for control measures to target specifically different patterns of consumption.

Correlation between octanol/water and liposome/water distribution coefficients and drug absorption of a set of pharmacologically active compounds.

Absorption and consequent therapeutic action are key issues in the development of new drugs by the pharmaceutical industry. In this sense, different models can be used to simulate biological membranes to predict the absorption of a drug. This work compared the octanol/water and the liposome/water models. The parameters used to relate the two models were the distribution coefficients between liposomes and water and octanol and water and the fraction of drug orally absorbed. For this study, 66 drugs were collected from literature sources and divided into four groups according to charge and ionization degree: neutral; positively charged; negatively charged; and partially ionized/zwitterionic. The results show a satisfactory linear correlation between the octanol and liposome systems for the neutral (R²= 0.9324) and partially ionized compounds (R²= 0.9367), contrary to the positive (R²= 0.4684) and negatively charged compounds (R²= 0.1487). In the case of neutral drugs, results were similar in both models because of the high fraction orally absorbed. However, for the charged drugs (positively, negatively, and partially ionized/zwitterionic), the liposomal model has a more-appropriate correlation with absorption than the octanol model. These results show that the neutral compounds only interact with membranes through hydrophobic bonds, whereas charged drugs favor electrostatic interactions established with the liposomes. With this work, we concluded that liposomes may be a more-appropriate biomembrane model than octanol for charged compounds.

Antimicrobial Bacterial Metabolites: Properties, Applications and Loading in Liposomes for Site-specific Delivery.

The high levels of antibiotic resistance registered worldwide have become a serious health problem, threatening the currently available treatments for a series of infectious diseases. With antibiotics becoming less and less effective, it is becoming increasingly difficult and, in some cases, impossible to treat patients with even common infectious diseases, such as pneumonia. The inability to meet the ever-increasing demand to control microbial infection requires both the search for new antimicrobials and improved site-specific delivery. On the one hand, bacterial secondary metabolites are known for their diverse structure and antimicrobial potential and have been in use for a very long time in diverse sectors. A good deal of research is produced annually describing new molecules of bacterial origin with antimicrobial properties and varied applications. However, very few of these new molecules reach the clinical phase and even fewer are launched in the market for use. In this review article, we bring together information on these molecules with potential for application, in particular, for human and veterinary medicine, and the potential added value of the use of liposomes as delivery systems for site-specific delivery of these drugs with the synergistic effect to overcome the risk of antibiotic resistance.

Prevalence of Cardiovascular Risk Factors among Young Adults (18-25 Years) in Mozambique.

The life course development of cardiovascular diseases (CVDs) and the undergoing epidemiological transition in Mozambique highlight the importance of monitoring the cardiovascular risk profile in young adults. Therefore, this study aims to estimate the prevalence of CVD risk factors in a population aged 18-25 years living in Mozambique. A total of 776 young adults from a nationally representative sample were evaluated in 2014/2015 following the World Health Organization's STEPwise approach to chronic disease risk factor surveillance. Current smoking was the most prevalent among rural men (10.8%, 95%CI: 6.3-17.8), and drinking was most prevalent among urban men (38.6%, 95%CI: 29.3-48.8). The proportion of young adults not engaging in at least 75 min of vigorous physical activity per week ranged between 14.5% in rural men and 61.6% in urban women. The prevalence of being overweight/obese and hypertension were highest among urban women (21.6%, 95%CI: 14.7-30.6) and urban men (25.2%, 95%CI: 15.9-37.6), respectively. Education >8 years (vs. none) was independently associated with lower odds of being a current smoker, and increased monthly household income was associated with increased odds of low levels of physical activity. This study shows that important CVD risk factors are already common in the young adult population of Mozambique.

Liposomes as a model for the biological membrane: studies on daunorubicin bilayer interaction.

In this study the interaction of the antitumoral drug daunorubicin with egg phosphatidylcholine (EPC) liposomes, used as a cell membrane model, was quantified by determination of the partition coefficient (K(p)). The liposome/aqueous-phase K(p) of daunorubicin was determined by derivative spectrophotometry and measurement of the zeta-potential. Mathematical models were used to fit the experimental data, enabling determination of K(p). In the partition of daunorubicin within the membrane both superficial electrostatic and inner hydrophobic interactions seem to be involved. The results are affected by the two types of interaction since spectrophotometry measures mainly hydrophobic interactions, while zeta-potential is affected by both interpenetration of amphiphilic charged molecules in the bilayer and superficial electrostatic interaction. Moreover, the degree of the partition of daunorubicin with the membrane changes with the drug concentration, due mainly to saturation factors. Derivative spectrophotometry and zeta-potential variation results, together with the broad range of concentrations studied, revealed the different types of interactions involved. The mathematical formalism applied also allowed quantification of the number of lipid molecules associated with one drug molecule.