Pseudoboehmite as a drug delivery system for acyclovir

Herpes simplex virus is among the most prevalent sexually transmitted infections. Acyclovir is a potent, selective inhibitor of herpes viruses and it is indicated for the treatment and management of recurrent cold sores on the lips and face, genital herpes, among other diseases. The problem of the oral bioavailability of acyclovir is limited because of the low permeability across the gastrointestinal membrane. The use of nanoparticles of pseudoboehmite as a drug delivery system in vitro assays is a promising approach to further the permeability of acyclovir release. Here we report the synthesis of high purity pseudoboehmite from aluminium nitrate and ammonium hydroxide containing nanoparticles, using the sol–gel method, as a drug delivery system to improve the systemic bioavailability of acyclovir. The presence of pseudoboehmite nanoparticles were verified by infrared spectroscopy, transmission electron microscopy, and X-ray diffraction techniques. In vivo tests were performed with Wistar rats to compare the release of acyclovir, with and without the addition of pseudoboehmite. The administration of acyclovir with the addition of pseudoboehmite increased the drug content by 4.6 times in the plasma of Wistar rats after 4 h administration. We determined that the toxicity of pseudoboehmite is low up to 10 mg/mL, in gel and the dried pseudoboehmite nanoparticles.The authors thank the Mackenzie Presbyterian University, Texas Tech University, Mack Pesquisa, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES), Cnpq, and FAPESP (grant 2010/19157-9 and grant 2017/22396-4) for the sponsorship to this project

Persistence and Adherence to Cardiovascular Medicines in Australia

BACKGROUND: The burden of cardiovascular disease is increasing, with many people treated for multiple cardiovascular conditions. We examined persistence and adherence to medicines for cardiovascular disease treatment or prevention in Australia. METHODS AND RESULTS: Using national dispensing claims for a 10% random sample of people, we identified adults (≥18 years) initiating antihypertensives, statins, oral anticoagulants, or antiplatelets in 2018. We measured persistence to therapy using a 60-day permissible gap, and adherence using the proportion of days covered up to 3 years from initiation, and from first to last dispensing. We reported outcomes by age, sex, and cardiovascular multimedicine use. We identified 83 687 people initiating antihypertensives (n=37 941), statins (n=34 582), oral anticoagulants (n=15 435), or antiplatelets (n=7726). Around one-fifth of people discontinued therapy within 90 days, with 50% discontinuing within the first year. Although many people achieved high adherence (proportion of days covered ≥80%) within the first year, these rates were higher when measured from first to last dispensing (40.5% and 53.2% for statins; 55.6% and 80.5% for antiplatelets, respectively). Persistence was low at 3 years (17.5% antiplatelets to 37.3% anticoagulants). Persistence and adherence increased with age, with minor differences by sex. Over one-third of people had cardiovascular multimedicine use (reaching 92% among antiplatelet users): they had higher persistence and adherence than people using medicines from only 1 cardiovascular group. CONCLUSIONS: Persistence to cardiovascular medicines decreases substantially following initiation, but adherence remains high while people are using therapy. Cardiovascular multimedicine use is common, and people using multiple cardiovascular medicines have higher rates of persistence and adherence

Rates of Low-Value Service in Australian Public Hospitals and the Association With Patient Insurance Status.

Importance: Low-value services have limited or no benefit to patients. Rates of low-value service in public hospitals may vary by patient insurance status, given that there may be different financial incentives for treatment of privately insured patients. Objective: To assess the variation in rates of 5 low-value services performed in Australian public hospitals according to patient funding status (ie, private or public). Design, Setting, and Participants: This retrospective cross-sectional study analyzed New South Wales public hospital data from January 2013 to June 2018. Patients included in the sample were over age 18 years and eligible to receive low-value services based on diagnoses and concomitant procedures. Data analysis was conducted from June to December 2020. Main Outcomes and Measures: Hospital-specific rates of low-value knee arthroscopic debridement, vertebroplasty for osteoporotic spinal fractures, hyperbaric oxygen therapy, oophorectomy with hysterectomy, and laparoscopic uterine nerve ablation for chronic pelvic pain were measured. For each measure, rates within each public hospital were compared by patient funding status descriptively and using multilevel models. Results: A total of 219 862 inpatients were included in analysis from 58 public hospitals across the 5 measures. A total of 38 365 (22 904 [59.7%] women; 12 448 [32.4%] aged 71-80 years) were eligible for knee arthroscopic debridement for osteoarthritis; 2520 (1924 [76.3%] women; 662 [26.3%] aged 71-80 years), vertebroplasty for osteoporotic spinal fractures; 162 285 (82 046 [50.6%] women; 28 255 [17.4%] aged 61-70 years), hyperbaric oxygen therapy; 15 916 (7126 [44.8%] aged 41-50 years), oophorectomy with hysterectomy; and 776 (327 [42.1%] aged 18-30 years), uterine nerve ablation for chronic pelvic pain. Overall rates of low-value services varied considerably between measures, with the lowest rate for hyperbaric oxygen therapy (0.3 procedures per 1000 inpatients [47 of 158 220 eligible inpatients]) and the highest for vertebroplasty (30.8 procedures per 1000 eligible patients [77 of 2501 eligible inpatients]). There was significant variation in rates between hospitals, with a few outlying hospitals (ie, <10), particularly for knee arthroscopy (range from 1.8 to 21.0 per 1000 eligible patients) and vertebroplasty (range from 13.1 to 70.4 per 1000 eligible patients), with higher numerical rates of low-value services among patients with private insurance than for those without. However, there was no association overall between patient insurance status and low-value services. Overall differences in rates among those with and without private insurance by individual procedure type were not statistically significant. Conclusions and Relevance: There was significant variation in rates of low-value services in public hospitals. While there was no overall association between private insurance and rate of low-value services, private insurance may be associated with low-value service rates in some hospitals. Further exploration of factors specific to local hospitals and practices are needed to reduce this unnecessary care

Urinary incontinence related to perineal muscle strength in the first trimester of pregnancy: cross-sectional study

Objective To analyze pelvic floor muscle strength (PFMS), urinary continence and quality of life related to urinary incontinence (UI) of women in the first trimester of pregnancy. Method Cross-sectional study with a sample of 500 women who started prenatal care in a complementary healthcare facility in Guarulhos, state of São Paulo, from 2012 and 2013. Pelvic floor muscle strength was evaluated through perineometry. The pregnant women who presented UI answered the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF). Results It was found that maternal age (OR=1.06; CI95% 1.02-1.11) and prior UI (OR=15.12; 95%CI 8.19-27.92) are the variables that, in tandem, best explain the occurrence of UI at the beginning of pregnancy. The mean score on the ICIQ-SF was 8.2 (SD=3.9), considered a moderate impact on quality of life. Conclusion Older pregnant women with prior UI are more likely to have UI in the first trimester of pregnancy.
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Integral field spectroscopy with SINFONI of VVDS galaxies. I. Galaxy dynamics and mass assembly at 1.2 < z < 1.6

Context. Identifying the main processes of galaxy assembly at high redshifts is still a major issue to understand galaxy formation and evolution at early epochs in the history of the Universe. Aims. This work aims to provide a first insight into the dynamics and mass assembly of galaxies at redshifts 1.2<z<1.6, the early epoch just before the sharp decrease of the cosmic star formation rate. Methods. We use the near-infrared integral field spectrograph SINFONI on the ESO-VLT under 0.65 seeing to obtain spatially resolved spectroscopy on nine emission line galaxies with 1.2<z<1.6 from the VIMOS VLT Deep Survey. We derive the velocity fields and velocity dispersions on kpc scales using the Halpha emission line. Results. Out of the nine star-forming galaxies, we find that galaxies distribute in three groups: two galaxies can be well reproduced by a rotating disk, three systems can be classified as major mergers and four galaxies show disturbed dynamics and high velocity dispersion. We argue that there is evidence for hierarchical mass assembly from major merger, with most massive galaxies with M>10^11Msun subject to at least one major merger over a 3 Gyr period as well as for continuous accretion feeding strong star formation. Conclusions. These results point towards a galaxy formation and assembly scenario which involves several processes, possibly acting in parallel, with major mergers and continuous gas accretion playing a major role. Well controlled samples representative of the bulk of the galaxy population at this key cosmic time are necessary to make further progress.Comment: 23 pages, 22 figures, accepted for publication in A&

Development of a rapid lateral flow immunoassay test for detection of exosomes previously enriched from cell culture medium and body fluids

Exosomes are cell-secreted nanovesicles (40–200 nm) that represent a rich source of novel biomarkers in the diagnosis and prognosis of certain diseases. Despite the increasingly recognized relevance of these vesicles as biomarkers, their detection has been limited due in part to current technical challenges in the rapid isolation and analysis of exosomes. The complexity of the development of analytical platforms relies on the heterogeneous composition of the exosome membrane. One of the most attractive tests is the inmunochromatographic strips, which allow rapid detection by unskilled operators. We have successfully developed a novel lateral flow immunoassay (LFIA) for the detection of exosomes based on the use of tetraspanins as targets. We have applied this platform for the detection of exosomes purified from different sources: cell culture supernatants, human plasma and urine. As proof of concept, we explored the analytical potential of this LFIA platform to accurately quantify exosomes purified from a human metastatic melanoma cell line. The one-step assay can be completed in 15 min, with a limit of detection of 8.54×105 exosomes/µL when a blend of anti-CD9 and anti-CD81 were selected as capture antibodies and anti-CD63 labelled with gold nanoparticles as detection antibody. Based on our results, this platform could be well suited to be used as a rapid exosome quantification tool, with promising diagnostic applications, bearing in mind that the detection of exosomes from different sources may require adaptation of the analytical settings to their specific composition.FICYT; Ministerio de Educación; Ministerio de Economía y Competitividad; Gobierno Regional de Asturias; Gobierno Regional de Madri

Extensional flow of hyaluronic acid solutions in an optimized micofluidic cross-slot device

We utilize a recently developed microfluidic device, the Optimized Shape Cross-slot Extensional Rheometer (OSCER), to study the elongational flow behavior and rheological properties of hyaluronic acid (HA) solutions representative of the synovial fluid (SF) found in the knee joint. The OSCER geometry is a stagnation point device that imposes a planar extensional flow with a homogenous extension rate over a significant length of the inlet and outlet channel axes. Due to the compressive nature of the flow generated along the inlet channels, and the planar elongational flow along the outlet channels, the flow field in the OSCER device can also be considered as representative of the flow field that arises between compressing articular cartilage layers of the knee joints during running or jumping movements. Full-field birefringence microscopy measurements demonstrate a high degree of localized macromolecular orientation along streamlines passing close to the stagnation point of the OSCER device, while micro-particle image velocimetry is used to quantify the flow kinematics. The stress-optical rule is used to assess the local extensional viscosity in the elongating fluid elements as a function of the measured deformation rate. The large limiting values of the dimensionless Trouton ratio, Tr ∼ O(50), demonstrate that these fluids are highly extensional-thickening, providing a clear mechanism for the load-dampening properties of SF. The results also indicate the potential for utilizing the OSCER in screening of physiological SF samples, which will lead to improved understanding of, and therapies for, disease progression in arthritis sufferers

Estimated Lifetime Cardiovascular, Kidney, and Mortality Benefits of Combination Treatment With SGLT2 Inhibitors, GLP-1 Receptor Agonists, and Nonsteroidal MRA Compared With Conventional Care in Patients With Type 2 Diabetes and Albuminuria

BACKGROUND: Sodium glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1 RA), and the nonsteroidal mineralocorticoid receptor antagonist (ns-MRA) finerenone all individually reduce cardiovascular, kidney, and mortality outcomes in patients with type 2 diabetes and albuminuria. However, the lifetime benefits of combination therapy with these medicines are not known. METHODS: We used data from 2 SGLT2i trials (CANVAS [Canagliflozin Cardiovascular Assessment] and CREDENCE [Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation]), 2 ns-MRA trials (FIDELIO-DKD [Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease] and FIGARO-DKD [Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and the Clinical Diagnosis of Diabetic Kidney Disease]), and 8 GLP-1 RA trials to estimate the relative effects of combination therapy versus conventional care (renin-angiotensin system blockade and traditional risk factor control) on cardiovascular, kidney, and mortality outcomes. Using actuarial methods, we then estimated absolute risk reductions with combination SGLT2i, GLP-1 RA, and ns-MRA in patients with type 2 diabetes and at least moderately increased albuminuria (urinary albumin:creatinine ratio ≥30 mg/g) by applying estimated combination treatment effects to participants receiving conventional care in CANVAS and CREDENCE. RESULTS: Compared with conventional care, the combination of SGLT2i, GLP-1 RA, and ns-MRA was associated with a hazard ratio of 0.65 (95% CI, 0.55–0.76) for major adverse cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death). The corresponding estimated absolute risk reduction over 3 years was 4.4% (95% CI, 3.0–5.7), with a number needed to treat of 23 (95% CI, 18–33). For a 50-year-old patient commencing combination therapy, estimated major adverse cardiovascular event–free survival was 21.1 years compared with 17.9 years for conventional care (3.2 years gained [95% CI, 2.1–4.3]). There were also projected gains in survival free from hospitalized heart failure (3.2 years [95% CI, 2.4–4.0]), chronic kidney disease progression (5.5 years [95% CI, 4.0–6.7]), cardiovascular death (2.2 years [95% CI, 1.2–3.0]), and all-cause death (2.4 years [95% CI, 1.4–3.4]). Attenuated but clinically relevant gains in event-free survival were observed in analyses assuming 50% additive effects of combination therapy, including for major adverse cardiovascular events (2.4 years [95% CI, 1.1–3.5]), chronic kidney disease progression (4.5 years [95% CI, 2.8–5.9]), and all-cause death (1.8 years [95% CI, 0.7–2.8]). CONCLUSIONS: In patients with type 2 diabetes and at least moderately increased albuminuria, combination treatment of SGLT2i, GLP-1 RA, and ns-MRA has the potential to afford relevant gains in cardiovascular and kidney event-free and overall survival