Trap Parameters for the Fast OSL Signal Component Obtained through Analytical Separation for Various Quartz Samples

Trap stability is essential in luminescence dating and thermochronometry. Trap depth and frequency factors determining the stability of the fast component of optically stimulated luminescence (OSL) in quartz, which is the most important in dating, have yet to be uniquely determined, especially for samples with an OSL signal not dominated by this component. One can determine them in OSL thermal depletion curve (OTDC) experiments. The separation of the fast OSL signal undisturbed by other OSL components is vital for obtaining accurate parameters for the traps of interest. This work presents a method of simultaneous thermal and optical stimulation using red light (620 nm) to separate the fast OSL component (the thermally modulated OSL method—TM-OSL). The OTDC experiment with the TM-OSL stimulation was used for the trap parameter determination on a variety of quartz samples, leading us to report for the first time, the trap parameters for the fast OSL component analytically separated in quartz from rock samples. The results obtained for these samples with the fast component of low intensity are consistent with those with an intensive fast OSL component. Results of OTDC measurements for all investigated quartz samples were tested for a wide range of irradiation doses.     

Molnupiravir When Used Alone Seems to Be Safe and Effective as Outpatient COVID-19 Therapy for Hemodialyzed Patients and Kidney Transplant Recipients

Background: Molnupiravir demonstrated an in vitro antiviral activity against positive-sense RNA viruses, including SARS-CoV-2. The study aimed to present the results of outpatient molnupiravir use in kidney transplant recipients and hemodialysis patients during the first months of 2022 in Poland. Methods: The retrospective observational cohort study at one kidney transplant center included 36 patients diagnosed with COVID-19 with an automated nucleic acid amplification test on nasopharyngeal swab specimens. All patients received molnupiravir for home-based therapy at a dose of 800 mg every 12 h orally for 5 days. Both kidney transplant recipients (n = 16) and hemodialysis patients (n = 20) presented a lot of comorbidities with a Charlson comorbidity index of 4.1 and 5.1, respectively. Results: Patients presented with fever, cough, and weakness followed by muscle and joint pain. Five kidney transplant recipients experienced acute kidney injury with a rise in serum creatinine level from 0.4 to 1.9 mg/dL. No serious side effects of molnupiravir therapy or interactions with immunosuppressive medications were observed. Symptoms of COVID-19 improved rapidly or resolved within 24–48 h of starting treatment. Conclusion: The study suggests the safety and efficacy of molnupiravir therapy alone early after the onset of SARS-CoV-2 infection, but further investigations should be performed to confirm our preliminary results. To the best of the authors’ knowledge, it is the first published report on molnupiravir use in end-stage kidney disease (ESKD) patients on hemodialysis and the third concerning kidney transplant recipients.     

HIV screening and linkage to care in a health department in Valencia,Spain: Lessons learned from a healthcare quality improvement project

Spain’s rate of new human immunodeficiency virus (HIV) diagnoses exceeds that of the European Economic Area average (8.6 vs 5.6:100,000 in 2018). The country has failed to meet the first of United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets for HIV control by 2020, with 87.0% of people living with HIV knowing their status, and late presentation rates of 47.6% and 51.5% country-wide and in the Valencian autonomous community, respectively. Advancing screening and linkage to care (SLTC) practices is necessary to effectively control the epidemic. The Valencia Viral Screening (CRIVALVIR) project adopted the TEST model for opportunistic and systematic HIV SLTC in individuals aged 18 to 80 who required blood work for any purpose, as of February 2019. SLTC was integrated into routine clinical workflow across primary care centers serving a population of 360,000 people in Valencia, Spain. Our project successfully upscaled total HIV testing by 194% to over 32,000 patients tested in 14 months. We found an overall prevalence of 0.13% (0.08–0.21) among those screened per protocol (n = 13,061), with foreign-born citizens presenting a 12.5 times significantly higher likelihood of acquiring HIV (95% confidence interval 4.63–33.96, P < .0001). We improved late presentation by 18.2 percentage points and prevented an estimated 58 to 70 new secondary infections. HIV screening of the general population in primary care is an effective strategy for achieving timely diagnosis and preventing new infections. Opportunistic, systematic, opt-out approaches are essential to control the HIV epidemic.     

The Assessment of the Hypothalamic-Pituitary-Adrenal Axis After Oncological Treatment in Pediatric Patients with Acute Lymphoblastic Leukemia

Objective:Oncologic treatment can affect the adrenal glands, which in stressful situations may lead to life threatening adrenal crisis. The aim of the study was to assess adrenal function in pediatric acute lymphoblastic leukemia (ALL) survivors and to identify the best markers for this assessment.Methods:Forty-three ALL survivors, mean age 8.5±3.6 years and 45 age and sex-matched healthy controls were recruited to the study. ALL patients were assessed once within five years following oncological treatment completion. Fasting blood samples were collected from all participants to measure: fasting blood glucose (FBG); cortisol; aldosterone; plasma renin activity (PRA); dehydroepiandrostendione-sulfate (DHEA-S); and adrenocorticotropic hormone (ACTH). Moreover, diurnal profile of cortisol levels and 24-hour urinary free cortisol (UFC) were assessed. ALL survivors underwent a test with 1 ug of synthetic ACTH.Results:The study revealed lower level of PRA (1.94±0.98 ng/mL/h vs 3.61±4.85 ng/mL/h, p=0.029) and higher FBG (4.6±0.38 mmol/L vs 4.41±0.39 mmol/L, p=0.018) in the ALL group compared to controls. UFC correlated with evening cortisol (p=0.015, r=0.26), midnight cortisol (p=0.002, r=0.33), and DHEA-S (p=0.004, r=0.32). UFC also correlated with systolic and diastolic blood pressure (p=0.033, r=0.23 and p=0.005, r=0.31, respectively). The ACTH test confirmed impaired adrenal function in 4/43 ALL survivors (9%). Two of the patients who needed permanent hydrocortisone replacement had low UFC, midnight cortisol and DHEA-S levels.Conclusion:These results highlight the importance of reviewing adrenal gland functionality after chemo/radiotherapy in ALL survivors. DHEA-S proved to be a good marker to assess the adrenal glands after oncological therapy. Post-treatment disturbances of the adrenal axis could be associated with metabolic complications.     

The Role of Stem Cells in the Therapy of Stroke

Background: Stroke is a major challenge in neurology due to its multifactorial genesis and irreversible consequences. Processes of endogenous post-stroke neurogenesis, although insufficient, may indicate possible direction of future therapy. Multiple research considers stem-cell-based approaches in order to maximize neuroregeneration and minimize post-stroke deficits. Objective: Aim of this study is to review current literature considering post-stroke stem-cell-based therapy and possibilities of inducing neuroregeneration after brain vascular damage. Methods: Papers included in this article were obtained from PubMed and MEDLINE databases. The following medical subject headings (MeSH) were used: “stem cell therapy”, “post-stroke neurogenesis”, “stem-cells stroke”, “stroke neurogenesis”, “stroke stem cells”, “stroke”, “cell therapy”, “neuroregeneration”, “neurogenesis”, “stem-cell human”, “cell therapy in human”. Ultimate inclusion was made after manual review of the obtained reference list. Results: Attempts of stimulating neuroregeneration after stroke found in current literature include supporting endogenous neurogenesis, different routes of exogenous stem cells supplying and extracellular vesicles used as a method of particle transport. Conclusion: Although further research in this field is required, post stroke brain recovery supported by exogenous stem cells seems to be promising future therapy revolutionizing modern neurology.     

Main-chain flexibility and hydrophobicity of ionenes strongly impact their antimicrobial activity: an extended study on drug resistance strains and Mycobacterium

The spread of antibiotic-resistant pathogens and the resurgence of tuberculosis disease are major motivations to search for novel antimicrobial agents. Some promising candidates in this respect are cationic polymers, also known as synthetic mimics of antimicrobial peptides (SMAMPs), which act through the membrane-lytic mechanism. Development of resistance toward SMAMPs is less likely than toward currently employed antibiotics; however, further studies are needed to better understand their structure–activity relationship. The main objective of this work is to understand the cross-influence of hydrophobicity, main-chain flexibility, and the topology of ionenes (polycations containing a cationic moiety within the main-chain) on activity. To fulfill this goal, a library of ionenes was developed and compared with previously investigated molecules. The obtained compounds display promising activity against the model microorganisms and drug-resistance clinical isolates, including Mycobacterium tuberculosis. The killing efficiency was also investigated, and results confirm a strong effect of hydrophobicity, revealing higher activity for molecules possessing the flexible linker within the polymer main-chain.

A high significance of the main chain flexibility and an unexpected effect of hydrophobicity on the biological activity in series of ionenes was observed. The most potent among the tested polycations showed high activity toward clinical bacterial isolates.     

Vasorelaxant effects and mechanisms of action of Heracleum sphondylium L. (Apiaceae) in rat thoracic aorta

Ethnopharmacological relevance

Aerial parts of Heracleum sphondylium L. (HS) are used in traditional medicine to treat hypertension. To provide pharmacological basis for this use, we investigated the vasorelaxant effects of a dichloromethane extract of HS (HSDE) and the mechanisms involved.

Materials and methods

Activity of HSDE was evaluated on rat isolated thoracic aortic rings.

Results

HSDE induced vasorelaxation in phenylephrine (PE, 10⁻⁶ mol/L) and high KCl—(6×10⁻² mol/L) pre-contracted aortic rings that was independent on the presence of endothelium. HSDE markedly decreased extracellular Ca²⁺-induced contraction in high-KCl and PE pre-challenged rings. It also inhibited the intracellular Ca²⁺ release sensitive to PE (10⁻⁶ M). The relaxant effect of HSDE were blunted by 4-amino-pyridine (4-AP, 10⁻³ mol/L), an inhibitor of voltage-dependent K⁺ channels.

Conclusion

Our results provide the first evidence that a dichloromethane extract of Heracleum sphondylium L. exhibits vasorelaxant properties through endothelium-independent mechanisms involving the inhibition of Ca²⁺ mobilization and changes in Kv channel conductances. These data argue for its use as antihypertensive therapy in traditional medicine.     

Design and Evaluation of Orally Dispersible Tablets Containing Amlodipine Inclusion Complexes in Hydroxypropyl-β-cyclodextrin and Methyl-β-cyclodextrin

The development of new orally dispersible tablets containing amlodipine (AML) inclusion complexes in hydroxypropyl-β-cyclodextrin (HP-β-CD) and in methyl-β-cyclodextrin (Me-β-CD) was studied. The methods of obtaining amlodipine and the physical and chemical properties of the inclusion complexes using the two cyclodextrins was investigated separately. Solid inclusion complexes were obtained by three methods: kneading, coprecipitation, and lyophilization, at a molar ratio of 1:1. For comparison, a physical mixture in the same molar ratio was prepared. The aim of the complexation process was to improve the drug solubility. As the lyophilization method leads to a complete inclusion of the drug in the guest molecule cavity, for both used cyclodextrins, these types of compounds were selected as active ingredients for the design of orally dispersible tablets. Subsequently, the formulation of the orodispersible tablets containing AML-HP-β-CD and AML-Me-β-CD inclusion complexes and quality parameters of the final formulation were evaluated. The results prove that F1 and F4 formulations, based on silicified microcrystalline cellulose, which contains insignificant proportions of very small or very large particles, had the lowest moisture degree (3.52% for F1 and 4.03% for F4). All of these demonstrate their porous structure, which led to good flowability and compressibility performances. F1 and F4 formulations were found to be better to manufacture orally dispersible tablets.