Synthesis and Pharmacological Characterization of Fluorescent Ligands Targeting the Angiotensin II Receptors Derived from Agonists, β-Arrestin-Biased Agonists, and Antagonists.

Angiotensin II (AngII) regulates cerebral circulation and binds with a similar affinity to AT and AT receptors. Biased AT agonists, such as TRV027, which are able to selectively activate β-arrestin while blocking the G pathway, appear promising as new therapeutics. New pharmacological tools are needed to further explore the impact of biased AT agonists on cells or tissues, such as the cerebral vessels.

Distinct trajectories of neuropsychiatric symptoms in the 12 months following traumatic brain injury (TBI): a TRACK-TBI study.

Background: Neuropsychiatric symptoms are common after traumatic brain injury (TBI) and often resolve within 3 months post-injury. However, the degree to which individual patients follow this course is unknown. We characterized trajectories of neuropsychiatric symptoms over 12 months post-TBI.

Autotrophic adaptive laboratory evolution of the acetogen Clostridium autoethanogenum delivers the gas-fermenting strain LAbrini with superior growth, products, and robustness.

Microbes able to convert gaseous one-carbon (C1) waste feedstocks are increasingly important to transition to the sustainable production of renewable chemicals and fuels. Acetogens are interesting biocatalysts since gas fermentation using Clostridium autoethanogenum has been commercialised. However, most acetogen strains need complex nutrients, display slow growth, and are not robust for bioreactor fermentations.

Follow-up for 3 years of a pediatric population diagnosed in 2018 with mother-to-child transmission of HIV in 8 Latin American countries in the PLANTAIDS cohort.

Introduction: The frequency of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) in Latin America has decreased considerably. However, new infections continue to be recorded, and the pediatric population remains one of the most vulnerable groups in this region. The main objective of the study was to describe the clinical, epidemiological and psychosocial characteristics of new diagnoses of HIV MTCT in 2018 in the PLANTAIDS network (Paediatric Network for Prevention, Early Detection and Treatment of HIV in Children) during the 3 years following diagnosis.

Realizing integration in structural biology: The 2022 ISBUC Annual Meeting.

This meeting report presents the 2022 Annual Meeting of the cluster for Integrative Structural Biology at the University of Copenhagen (ISBUC) and discusses the cluster approach to interdisciplinary research management. This approach successfully facilitates cross-faculty and inter-departmental collaboration. Innovative integrative research collaborations ignited by ISBUC, as well as research presented at the meeting, are showcased.

DCIS: When is accelerated partial breast irradiation an option? A meta-analysis on outcomes and eligibility.

Background: The natural history of DCIS may not be progression to invasive breast cancer (IBC). Accelerated partial breast irradiation (APBI) has emerged as an alternative to whole breast radiotherapy (WBRT). The purpose of this study was to assess the impact of APBI on DCIS patients.

: The impact of sociodemographic, health history, and psychological dimensions on Puerto Rican adults.

Introduction: (ADN) is a cultural syndrome prevalent in Puerto Ricans characterized as an episode of intense emotional upset due to overwhelming stress.

Methods: The , developed at the Center for the Study and Treatment for Fear and Anxiety (CETMA), served as the diagnostic tool for this retrospective secondary data analysis. We evaluated three models regarding ADN's function as a marker of (1) sociodemographic vulnerability, (2) health history risk, and (3) psychological vulnerability.

Estimating COVID-19 cases in Puerto Rico using an automated surveillance system.

Due to concerns regarding limited testing and accuracy of estimation of COVID-19 cases, we created an automated surveillance system called "Puerto Rico Epidemiological Evaluation and Prevention of COVID-19 and Influenza" (PREPCOVI) to evaluate COVID-19 incidence and time trends across Puerto Rico. Automated text message invitations were sent to random phone numbers with Puerto Rican area codes. In addition to reported COVID-19 test results, we used a published model to classify cases from specific symptoms (loss of smell and taste, severe persistent cough, severe fatigue, and skipped meals).

A Photoswitchable Ligand Targeting the β -Adrenoceptor Enables Light-Control of the Cardiac Rhythm.

Catecholamine-triggered β-adrenoceptor (β-AR) signaling is essential for the correct functioning of the heart. Although both β - and β -AR subtypes are expressed in cardiomyocytes, drugs selectively targeting β -AR have proven this receptor as the main target for the therapeutic effects of beta blockers in the heart. Here, we report a new strategy for the light-control of β -AR activation by means of photoswitchable drugs with a high level of β -/β -AR selectivity.

The impact of prenatal maternal stress due to potentially traumatic events on child temperament: A systematic review.

The objective of the current study was to complete a systematic review of the relationship between prenatal maternal stress due to potentially traumatic events (PTEs) and child temperament. Eligible studies through June 2020 were identified utilizing a search strategy in PubMed and PsycInfo. Included studies examined associations between prenatal maternal stress due to PTE and child temperament.

Coaching tailored by stages: A valuable educational strategy to achieve independence in research.

This study presents an individualized coaching approach tailored to the stages of proximity of promising scientists interested in becoming independently funded researchers in the context of a minority-serving institution. This strategy defined the participant's stage of proximity by their number of first-author publications in peer-reviewed journals and their track record in submitting research grants. We argue that coaching tailored by stages is an asset to maintain the enthusiasm, persistence, and positive attitude of promising scientists as they try to reach independent investigator status.

Normal cognitive test scores cannot be interpreted as accurate measures of ability in the context of failed performance validity testing: A symptom- and detection-coached simulation study.

While use of performance validity tests (PVTs) has become a standard of practice in neuropsychology, there are differing opinions regarding whether to interpret cognitive test data when standard scores fall within normal limits despite PVTs being failed. This study is the first to empirically determine whether normal cognitive test scores underrepresent functioning when PVTs are failed. Participants, randomly assigned to either a simulated malingering group ( = 50) instructed to mildly suppress test performances or a best-effort/control group ( = 50), completed neuropsychological tests which included the North American Adult Reading Test (NAART), California Verbal Learning Test - 2 Edition (CVLT-II), and Test of Memory Malingering (TOMM).

Ultrabright Fluorescent Organic Nanoparticles Based on Small-Molecule Ionic Isolation Lattices*.

Ultrabright fluorescent nanoparticles (NPs) hold great promise for demanding bioimaging applications. Recently, extremely bright molecular crystals of cationic fluorophores were obtained by hierarchical coassembly with cyanostar anion-receptor complexes. These small-molecule ionic isolation lattices (SMILES) ensure spatial and electronic isolation to prohibit aggregation quenching of dyes.

Public Health Academic Alliance for COVID-19 Response: The Role of a National Medical Task Force in Puerto Rico.

Alliances between the government and academic communities can be a key component of the public health response to an emergency such as the coronavirus disease 2019 (COVID-19) pandemic. The Governor of Puerto Rico designated the Puerto Rico Medical Task Force (MTF) COVID-19 to provide direct guidance and evaluation of the government response to the epidemic in Puerto Rico. Several work groups were formed within the MTF to create protocols and provide evidence-based recommendations on different public health aspects.

Intrinsic anti-Stokes emission in living HeLa cells.

Intrinsic fluorescence of biological material, also called auto-fluorescence, is a well-known phenomenon and has in recent years been used for imaging, diagnostics and cell viability studies. Here we show that in addition to commonly observed auto-fluorescence, intrinsic anti-Stokes emission can also be observed under 560 nm or 633 nm excitation. The anti-Stokes emission is shown to be spatially located on/in the mitochondria.

Costs and cost-effectiveness of three point-of-use water treatment technologies added to community-based treatment of severe acute malnutrition in Sindh Province, Pakistan.

Background: Severe acute malnutrition (SAM) is a major global public health concern. Despite the cost-effectiveness of treatment, ministries of health are often unable to commit the required funds which limits service coverage.

Objective: A randomised controlled trial was conducted in Sindh Province, Pakistan, to assess whether adding a point of use water treatment to the treatment of SAM without complications improved its cost-effectiveness.

Evaluation of the cost-effectiveness of the treatment of uncomplicated severe acute malnutrition by lady health workers as compared to an outpatient therapeutic feeding programme in Sindh Province, Pakistan.

Background: Due to the limited evidence of the cost-effectiveness of Community Health Workers (CHW) delivering treatment for severe acute malnutrition (SAM), there is a need to better understand the costs incurred by both implementing institutions and beneficiary households. This study assessed the costs and cost-effectiveness of treatment for cases of SAM without complications delivered by government-employed Lady Health Workers (LHWs) and complemented with non-governmental organisation (NGO) delivered outpatient facility-based care compared with NGO delivered outpatient facility-based care only alongside a two-arm randomised controlled trial conducted in Sindh Province, Pakistan.

Methods: An activity-based cost model was used, employing a societal perspective to include costs incurred by beneficiaries and the wider community.

Mechanisms of PDZ domain scaffold assembly illuminated by use of supported cell membrane sheets.

PDZ domain scaffold proteins are molecular modules orchestrating cellular signalling in space and time. Here, we investigate assembly of PDZ scaffolds using supported cell membrane sheets, a unique experimental setup enabling direct access to the intracellular face of the cell membrane. Our data demonstrate how multivalent protein-protein and protein-lipid interactions provide critical avidity for the strong binding between the PDZ domain scaffold proteins, PICK1 and PSD-95, and their cognate transmembrane binding partners.

Promoting Diversity in the Clinical and Translational Research Workforce.

The positive impact of diversity in increasing the effectiveness of the research workforce has been undeniably demonstrated to be an essential element for achieving health equity. Diversity is also instrumental for the research workforce to advance discovery, eliminate health disparities, improve minority health and achieve effective patient-centered outcomes in the quest for better health. One of the sustainable ways to achieve diversity in the workforce is through training, education and career development of all interested individuals including minority, underserved, underrepresented and populations with special needs.

Costs and cost-efficiency of a mobile cash transfer to prevent child undernutrition during the lean season in Burkina Faso: a mixed methods analysis from the MAM'Out randomized controlled trial.

Background: This study assessed the costs and cost-efficiency of a mobile cash transfer implemented in Tapoa Province, Burkina Faso in the MAM'Out randomized controlled trial from June 2013 to December 2014, using mixed methods and taking a societal perspective by including costs to implementing partners and beneficiary households.

Methods: Data were collected via interviews with implementing staff from the humanitarian agency and the private partner delivering the mobile money, focus group discussions with beneficiaries, and review of accounting databases. Costs were analyzed by input category and activity-based cost centers.

Cost-effectiveness of the treatment of uncomplicated severe acute malnutrition by community health workers compared to treatment provided at an outpatient facility in rural Mali.

Background: The Malian Nutrition Division of the Ministry of Health and Action Against Hunger tested the feasibility of integrating treatment of severe acute malnutrition (SAM) into the existing Integrated Community Case Management package delivered by community health workers (CHWs). This study assessed costs and cost-effectiveness of CHW-delivered care compared to outpatient facility-based care.

Methods: Activity-based costing methods were used, and a societal perspective employed to include all relevant costs incurred by institutions, beneficiaries and communities.

Visual Understanding of Light Absorption and Waveguiding in Standing Nanowires with 3D Fluorescence Confocal Microscopy.

Semiconductor nanowires are promising building blocks for next-generation photonics. Indirect proofs of large absorption cross sections have been reported in nanostructures with subwavelength diameters, an effect that is even more prominent in vertically standing nanowires. In this work we provide a three-dimensional map of the light around vertical GaAs nanowires standing on a substrate by using fluorescence confocal microscopy, where the strong long-range disruption of the light path along the nanowire is illustrated.

Rapid Prototyping of Polymeric Nanopillars by 3D Direct Laser Writing for Controlling Cell Behavior.

Mammalian cells have been widely shown to respond to nano- and microtopography that mimics the extracellular matrix. Synthetic nano- and micron-sized structures are therefore of great interest in the field of tissue engineering, where polymers are particularly attractive due to excellent biocompatibility and versatile fabrication methods. Ordered arrays of polymeric pillars provide a controlled topographical environment to study and manipulate cells, but processing methods are typically either optimized for the nano- or microscale.

Membrane curvature regulates ligand-specific membrane sorting of GPCRs in living cells.

The targeted spatial organization (sorting) of Gprotein-coupled receptors (GPCRs) is essential for their biological function and often takes place in highly curved membrane compartments such as filopodia, endocytic pits, trafficking vesicles or endosome tubules. However, the influence of geometrical membrane curvature on GPCR sorting remains unknown. Here we used fluorescence imaging to establish a quantitative correlation between membrane curvature and sorting of three prototypic class A GPCRs (the neuropeptide Y receptor Y2, the β adrenergic receptor and the β adrenergic receptor) in living cells.

Mapping cell behavior across a wide range of vertical silicon nanocolumn densities.

Over the past decade, vertical nanostructures have provided novel approaches for biomedical applications such as intracellular delivery/detection, specific cell capture, membrane potential measurement, and cellular activity regulation. Although the feasibility of the vertical nanostructures as a new biological tool has been thoroughly demonstrated, a better understanding of cell behavior on vertical nanostructures, in particular the effects of geometry, is essential for advanced applications. To investigate the cell behavior according to the variation of the spacing between vertical nanostructures, we have interfaced fibroblasts (NIH3T3) with density-controlled vertical silicon nanocolumn arrays (vSNAs).