Self-Assembly of Ultrasmall 3D Architectures of (l)-Acyclic Threoninol Nucleic Acids with High Thermal and Serum Stability.

The primary challenge of implementing DNA nanostructures in biomedical applications lies in their vulnerability to nuclease degradation and variations in ionic strength. Furthermore, the size minimization of DNA and RNA nanostructures is limited by the stability of the DNA and RNA duplexes. This study presents a solution to these problems through the use of acyclic (l)-threoninol nucleic acid (aTNA), an artificial acyclic nucleic acid, which offers enhanced resilience under physiological conditions.

Dual-Targeting of the HER2 Cancer Receptor with an Antibody-Directed Enzyme and a Nanobody-Guided MMAE Prodrug Scaffold.

Antibody-enzyme conjugates have shown potential as tissue-specific prodrug activators by antibody-directed enzyme prodrug therapy (ADEPT), but the approach met challenges clinically due to systemic drug release. Here, we report a novel dual-targeting ADEPT system (DuADEPT) which is based on active cancer receptor targeting of both a trastuzumab-sialidase conjugate (Tz-Sia) and a highly potent sialidase-activated monomethyl auristatin E (MMAE) prodrug scaffold. The scaffold is based on a four-way junction of the artificial nucleic acid analog acyclic (L)-threoninol nucleic acid ((L)-aTNA) which at the ends of its four arms carries one nanobody targeting HER2 and three copies of the prodrug.

Synthesis of peptide-siRNA conjugates via internal sulfonylphosphoramidate modifications and evaluation of their in vitro activity.

Conjugates of therapeutic oligonucleotides (ONs) including peptide conjugates, provide a potential solution to the major challenge of specific tissue delivery faced by this class of drugs. Conjugations are often positioned terminal at the ONs, although internal placement of other chemical modifications are known to be of critical importance. The introduction of internal conjugation handles in chemically modified ONs require highly specialized and expensive nucleoside phosphoramidites.

Vascular Effects, Potential Pathways and Mediators of Fetal Exposure to Alcohol and Cigarette Smoking during Pregnancy: A Narrative Review.

(1) Background: Programming of atherosclerosis results in vascular structure and function alterations, which may be attributed to fetal exposure to maternal tobacco smoking, alcohol consumption and several lifestyle factors in the first few years of life. This review aims to study the effects of teratogen exposure in utero on vascular dysfunction in offspring and consider mediators and pathways originating from the fetal environment. (2) Methods: Eligible studies were identified in the PubMed, Scopus and Web of Science databases.

The role of HIV/hepatitis B virus/hepatitis C virus RNA+ triple infection in end-stage liver disease and all-cause mortality in Europe.

Background: There are limited data on end-stage liver disease (ESLD) and mortality in people with HIV (PWH) coinfected with both hepatitis B virus (HBV) and hepatitis C virus (HCV).

Methods: All PWH aged greater than 18 under follow-up in EuroSIDA positive for HBsAg (HBV), and/or HCVRNA+, were followed from baseline (latest of 1 January 2001, EuroSIDA recruitment, known HBV/HCV status) to ESLD, death, last visit, or 31 December 2020. Follow-up while HCVRNA- was excluded.

Effect of maternal cigarette smoking and alcohol consumption during pregnancy on birth weight and cardiometabolic risk factors in infants, children and adolescents: a systematic review protocol.

Introduction: Tobacco smoking and alcohol consumption during pregnancy are particularly prevalent in low socioeconomic status populations, with an adverse association with birth outcomes and cardiometabolic risk factors. However, the direct and indirect effects of prenatal cigarette smoking and alcohol consumption during pregnancy on cardiometabolic risk in offspring have been rather inconsistent. This may be attributed to multiple factors, such as the amount and timing of exposure to tobacco smoking and alcohol during pregnancy; the influence of maternal, environmental and socioeconomic factors; or how risk factors were defined by individual researchers and studies.

Therapy Dogs' and Handlers' Behavior and Salivary Cortisol During Initial Visits in a Complex Medical Institution: A Pilot Study.

Therapy dogs provide health benefits for individuals who suffer from illnesses, such as dementia, depression, loneliness, and aggression. Therapy dogs' impact on human health has been thoroughly studied; however, studies on dog welfare have been limited. Additionally, as dogs have evolved with humans, they have learned to read non-verbal social cues.

The effects of exposure to teratogens on organ size: a prospective paediatric study.

In low-income countries, prospective data on combined effects of in utero teratogen exposure are lacking and necessitates new research. The aim of the present study was to explore the effect of in utero teratogen exposure on the size of the kidneys and pancreas 5 years after birth in a low-income paediatric population. Data was collected from 500 mother-child pairs from a low-income setting.

The Impact of a 20-Minute Animal-Assisted Activity Session on the Physiological and Emotional States in Patients With Fibromyalgia.

Objective: To study the direct physiological and emotional impact of an animal-assisted activity (AAA) session (a form of complementary and integrative medicine) in patients with fibromyalgia (FM).

Patients And Methods: The study population consisted of 221 participants with FM who were attending Mayo Clinic's Fibromyalgia Treatment Program between August 5, 2017, and September 1, 2018. This was a randomized controlled trial.

Physiological State of Therapy Dogs during Animal-Assisted Activities in an Outpatient Setting.

Therapy dogs are increasingly being incorporated into numerous clinical settings. However, there are only a handful of studies that have focused on the impact of animal-assisted activity or therapy sessions on the wellbeing of the therapy dogs. Furthermore, these studies show mixed results.

Optimizing delivery to meet demand for integrative medicine services in an academic hospital setting: A pilot study.

Context: A rapidly growing body of evidence shows the positive benefits of integrative medicine (IM) services for patients in hospital-based settings. IM therapies, such as acupuncture, massage, meditation and relaxation, and animal-assisted therapy, reduce symptom burden of pain, anxiety, and stress and increase sense of well-being and satisfaction in hospitalized patients. Current challenges facing hospitals are to move beyond proof-of-concept studies and to provide hospital-based IM therapies.

Observation of persistent species temperature separation in inertial confinement fusion mixtures.

The injection and mixing of contaminant mass into the fuel in inertial confinement fusion (ICF) implosions is a primary factor preventing ignition. ICF experiments have recently achieved an alpha-heating regime, in which fusion self-heating is the dominant source of yield, by reducing the susceptibility of implosions to instabilities that inject this mass. We report the results of unique separated reactants implosion experiments studying pre-mixed contaminant as well as detailed high-resolution three-dimensional simulations that are in good agreement with experiments.

teratogen exposure and cardiometabolic risk in 5-year-old children: a prospective pediatric study.

Background: Aorta and carotid intima-media thickness (IMT) is a measure of subclinical atherosclerosis and useful to assess cardiometabolic risk in the young. The milieu may involve cardiometabolic programing and the development of cardiometabolic risk factors in children. Maternal smoking, alcohol consumption, and micronutrient deficiencies during pregnancy influence the development of the cardiovascular system through a process of DNA methylation.

Canine-Assisted Therapy in Hospitalized Patients Awaiting Heart Transplantation.

Objectives: Patients awaiting heart transplantation can be listed for prolonged periods of time and, as a result, the prevalence of anxiety and depression is high. Our study evaluates the feasibility of canine-assisted therapy (CAT) in this population.

Methods: A prospective, multicenter study was performed on all status 1a patients admitted during a 12-month period to await transplantation.

A Population-Based Surveillance Study on the Epidemiology of Hepatitis C in Estonia.

The hepatitis C virus (HCV)-infected patients serve as a reservoir for transmission of the disease to others and are at risk of developing chronic hepatitis C, cirrhosis, and hepatocellular carcinoma. Although the epidemiological data of high rate HCV infection have been obtained in many countries, such data are insufficient in Estonia. Therefore, the aim of the study was to analyze country-specific data on HCV patients.

Variation in antiretroviral treatment coverage and virological suppression among three HIV key populations.

Objectives: We assessed differences in antiretroviral treatment (ART) coverage and virological suppression across three HIV key populations, as defined by self-reported HIV transmission category: sex between men, injection drug use (IDU) and heterosexual transmission.

Design: A multinational cohort study.

Methods: Within the EuroSIDA study, we assessed region-specific percentages of ART-coverage among those in care and virological suppression (<500 copies/ml) among those on ART, and analysed differences between transmission categories using logistic regression.

Diagnostic accuracy of the ADOS and ADOS-2 in clinical practice.

The Autism Diagnostic Observation Schedule is a semi-structured, standardized assessment tool for individuals with suspected autism spectrum disorders (ASD) and is deemed to be part of the gold standard for diagnostic evaluation. Good diagnostic accuracy and interpersonal objectivity have been demonstrated for the ADOS in research setting. The question arises whether this is also true for daily clinical practice and whether diagnostic accuracy depends on specialized experience in the diagnostic evaluation.

Uptake of tenofovir-based antiretroviral therapy among HIV-HBV-coinfected patients in the EuroSIDA study.

Background: According to guidelines all HIV-HBV-coinfected patients should receive tenofovir-based combination antiretroviral therapy (cART). We aimed to investigate uptake and outcomes of tenofovir-based cART among HIV-HBV patients in the EuroSIDA study.

Methods: All hepatitis B surface antigen (HBsAg)+ patients followed up after 1 March 2002 were included.

Incidence of cancer and overall risk of mortality in individuals treated with raltegravir-based and non-raltegravir-based combination antiretroviral therapy regimens.

Objectives: There are currently few data on the long-term risk of cancer and death in individuals taking raltegravir (RAL). The aim of this analysis was to evaluate whether there is evidence for an association.

Methods: The EuroSIDA cohort was divided into three groups: those starting RAL-based combination antiretroviral therapy (cART) on or after 21 December 2007 (RAL); a historical cohort (HIST) of individuals adding a new antiretroviral (ARV) drug (not RAL) to their cART between 1 January 2005 and 20 December 2007, and a concurrent cohort (CONC) of individuals adding a new ARV drug (not RAL) to their cART on or after 21 December 2007.

Ultraviolet luminosity density of the universe during the epoch of reionization.

The spatial fluctuations of the extragalactic background light trace the total emission from all stars and galaxies in the Universe. A multiwavelength study can be used to measure the integrated emission from first galaxies during reionization when the Universe was about 500 million years old. Here we report arcmin-scale spatial fluctuations in one of the deepest sky surveys with the Hubble Space Telescope in five wavebands between 0.

On the origin of near-infrared extragalactic background light anisotropy.

Extragalactic background light (EBL) anisotropy traces variations in the total production of photons over cosmic history and may contain faint, extended components missed in galaxy point-source surveys. Infrared EBL fluctuations have been attributed to primordial galaxies and black holes at the epoch of reionization (EOR) or, alternately, intrahalo light (IHL) from stars tidally stripped from their parent galaxies at low redshift. We report new EBL anisotropy measurements from a specialized sounding rocket experiment at 1.

Near-infrared background anisotropies from diffuse intrahalo light of galaxies.

Unresolved anisotropies of the cosmic near-infrared background radiation are expected to have contributions from the earliest galaxies during the epoch of reionization and from faint, dwarf galaxies at intermediate redshifts. Previous measurements were unable to pinpoint conclusively the dominant origin because they did not sample spatial scales that were sufficiently large to distinguish between these two possibilities. Here we report a measurement of the anisotropy power spectrum from subarcminute to one-degree angular scales, and find the clustering amplitude to be larger than predicted by the models based on the two existing explanations.

Antiretroviral therapy (ART) adherence and correlates to nonadherence among people on ART in Estonia.

There are little data on antiretroviral therapy (ART) adherence among patients in Eastern Europe, despite the high incidence of HIV infection and the growing number of HIV-infected individuals who are being prescribed ART. The aim of this study was to measure rates of adherence to ART and factors associated with nonadherence among patients receiving care at an outpatient HIV clinic in Estonia. The study was based on cross-sectional data from a convenience sample of 144 patients receiving outpatient HIV care.