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005). In group 1, decreased GCL thickness was statistically significantly correlated with increased aqueous flare intensity, enlarged FAZ area, and enlarged capillary non-flow area (p less then .005).Conclusion The results demonstrated a correlation of the retinal neurodegeneration with the aqueous flare levels and macular ischemia indices in the early stages of diabetic retinopathy. This finding supports the role of inflammation in the pathogenesis of diabetic retinal neuropathy.

Following percutaneous exposure to the nerve agent VX, the remaining intact agent within the skin after decontamination is of great concern. Consequently, this leads to prolonged agent release to the blood circulation resulting in sustained intoxication, which may complicate the medical management. The decontamination procedure used should therefore possess the ability for agent removal both on and within the skin. The efficacy of three decontamination procedures was evaluated by measuring VX and the primary degradation product ethyl methyl phosphonic acid (EMPA) penetrated through human skin and the amount remaining within the skin.

Decontamination was initiated 5 min post-exposure to VX on human dermatomed skin. Experiments were conducted using an

skin penetration model and the amount remaining within the skin was determined by combining the tape-stripping technique and acetylcholinesterase activity measurements.

In control experiments without decontamination, higher amounts of VX were recovered indation properties are important. In addition, the "wash-in" effect by using soapy water may enhance VX release to the blood circulation.Six months of supplementation with a multi-ingredient nutrition supplement was investigated in older adults with low skeletal muscle mass given the recently purported benefits of such approaches. Community-dwelling older adults (age, 74.9 ± 3.6 y; M/F, 18/19) participated in a double-blind, placebo-controlled, randomized trial involving daily consumption of either fruit juice placebo (PLA) or supplement (SUPP) in the form of a 200-mL carton of a juice-based emulsion of long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) (3000 mg as 1500 mg docosahexaenoic acid and 1500 mg eicosapentaenoic acid), whey protein isolate (8 g), vitamin D3 (400 IU), and resveratrol (150 mg). Body composition, physical function, and circulating markers of metabolic health were assessed at baseline (PRE), and after 3 (MID) and 6 (POST) months of supplementation. Lean body mass (LBM) was unchanged in either group, but fat mass increased in SUPP by 1.41 (0.75, 2.07) kg at POST (+6.4%; p  less then  .001; d = 0.20). Hand-grip strength was maintained in SUPP, but declined in PLA by 2.50 (0.81, 4.19) kg at POST (-6.8%; p = .002; d = 0.38). H151 Short physical performance battery score was unchanged in PLA, but increased in SUPP by 1.13 (0.41, 1.84) above PRE at POST (p = .001; d = 0.47). Circulating markers of metabolic health were unchanged in response to the intervention in either PLA or SUPP. Long-term supplementation with an LC n-3 PUFA-rich multi-ingredient nutrition supplement demonstrates potential efficacy for improving physical function in older adults in the absence of exercise training and independent of a change in LBM.

The lungs possess many xenobiotic metabolizing enzymes which influence the pharmacokinetics and safety of inhaled medicines. Anticipating metabolism in the lungs provides an opportunity to optimize new inhaled medicines and overcome challenges in their development.

This article summarizes current knowledge on xenobiotic metabolizing enzymes in the lungs. The impact of metabolism on inhaled medicines is considered with examples of how this impacts small molecules, biologics and macromolecular formulation excipients. Methods for measuring and predicting xenobiotic lung metabolism are critically reviewed and the potential for metabolism to influence inhalation toxicology is acknowledged.

Drugs can be optimized by molecular modification to (i) reduce systemic exposure using a 'soft drug' approach, (ii) improve bioavailability by resisting metabolism, or (iii) use a prodrug approach to overcome pharmacokinetic limitations. Drugs that are very labile in the lungs may require a protective formulation. Some drun silico models.Background Statins have extensive hepatic metabolism and can have multiple pharmacological interactions. The aim was to identify the main pharmacokinetic interactions between statins and their comedications in a group of patients from Colombia.Research design and methods A cross-sectional study of pharmacokinetic interactions in patients treated with statins who were identified from a population database. The interactions were documented using the Lexicomp® database.Results A total of 123,026 patients with statin prescriptions were identified, with a mean age of 68.4 ± 11.5 years; 57.1% were women, and 81.6% received atorvastatin. A total of 19.4% (n = 23.831) of patients presented pharmacological interactions. Some 15,474 (12.6%) had interactions classified as category C, 7.4% (n = 9077) as category D, and 0.5% (n = 660) as category X. 36.8% of the patients with lovastatin prescriptions had some interaction. Age older than 65 years, male sex, residence in capital cities, comorbidities, endocrine pathologies and HIV were associated with an increase in the probability of having contraindicated or risky interactions.Conclusions Important interactions between statins and other medications were more common in adults over 65 years of age and those with endocrine comorbidities or HIV infection. This knowledge should help when proposing solutions that reduce the risk of adverse reactions.

Disease prevention and improving vaccination coverage in Europe are key elements contributing to resilient health systems and ensuring better health outcomes for all. The aim of this study was to describe the immunization funding landscape across all European Union 28 countries (EU28).

Data collected in a targeted literature review supported descriptive analysis on the different indicators that were looked at vaccines included in the EU28 national immunization programs (NIP), national immunization funding, immunization funding per capita (2015-2019) and percentage of healthcare budget allocated to immunization.

Immunization funding represents a small proportion of total healthcare spend in Europe (median 0.3%). In the context of the current COVID-19 pandemic, demographic changes and the potential introduction of new vaccines; the need for adequate financing of immunization programs will be important, to establish resilient immunization systems and provide sustainable protection of the population against vaccine preventable diseases.

Immunization funding represents a small proportion of total healthcare spend in Europe (median 0.3%). In the context of the current COVID-19 pandemic, demographic changes and the potential introduction of new vaccines; the need for adequate financing of immunization programs will be important, to establish resilient immunization systems and provide sustainable protection of the population against vaccine preventable diseases.Introduction Blood group antigens are defined by an immune response that generates antibodies against a red blood cell molecule. Antibodies against these antigens can be associated with hemolytic transfusion reactions. However, difficulties can arise when developing antibodies against antigens through the use of peptide sequences alone. Three-dimensional representations (models) of the molecular structure of antigen-bearing proteins can provide valuable insights into tertiary structures and their consequent antigenicity. This can be achieved through predictive computational modeling to produce both structural and molecular dynamics models of blood group proteins.Areas covered Authors discuss the use of molecular dynamic simulations on existing structures, as well as the use of computational modeling techniques in the development of protein models lacking preexisting data. Finally, the authors discuss specific examples of the use of computationally derived models of the MNS blood group system and its use in attempts to produce antibodies against MNS proteins.Expert opinion Although in silico techniques have limitations, computer-based predictive models can inform the direction of research into blood group proteins. It is to be expected that as computer-based techniques grow more powerful these contributions will be even more significant.

Hairy cell leukemia-variant (HCL-V) is a rare B-cell neoplasm arising or homing primarily in the spleen. It has been considered in the WHO classification of Hemopoietic and Lymphoid Tumors as a provisional entity since 2008 and included under the umbrella of unclassifiable splenomegalic B-cell leukemia/lymphomas. The diagnosis is a challenge to hematopathologists and management of these patients by the clinicians is difficult due to the lack of diagnostic and therapeutic guidelines and prospective studies.

This manuscript is a comprehensive review of the clinical features, pathology, immunophenotypic profile, genomic alterations and therapeutic options of HCL-V. Diagnostic and therapeutic dilemmas are extensively outlined considering the information derived from a literature search covering from 1980 to 2019. Integration of all the data is needed and recommended for establishing the diagnosis of this leukemia.

More extensive information of genomic aberrations underlying the pathogenesis of the disease would be a solid stone for the diagnosis. To this end, a collaborative work among scientists and pathologists from different centers is required and expected. In turn, this might have a relevant clinical translation by allowing to identify putative targets for therapy and to improve the outlook of these patients.

More extensive information of genomic aberrations underlying the pathogenesis of the disease would be a solid stone for the diagnosis. To this end, a collaborative work among scientists and pathologists from different centers is required and expected. In turn, this might have a relevant clinical translation by allowing to identify putative targets for therapy and to improve the outlook of these patients.

Perimenopause is associated with declines in attention, working memory and verbal memory; however, there are significant individual differences. Further, the contributions of hormones and menopausal symptoms to domain-specific cognitive functions remain unknown. This longitudinal study aimed to determine whether there were distinct cognitive profiles in perimenopause and to identify factors associated with each profile.

In a sample of 85 women evaluated over 400 bi-annual visits, we administered a comprehensive neuropsychological battery, assessed menopausal symptoms and measured 17β-estradiol and follicle stimulating hormone. Multilevel latent profile analysis was used to identify cognitive profiles. Regressions were conducted to determine differences in hormones and symptoms by profile after adjusting for Stages of Reproductive Aging Workshop + 10 (STRAW + 10) stage and demographic factors.

Perimenopausal cognitive profiles consisted of cognitively normal (Profile 1;

 = 162), weaknesses in verbal learning and memory (Profile 2;

 = 94), strengths in verbal learning and memory (Profile 3;

 = 98) and strengths in attention and executive function (Profile 4;

 = 61).

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