Interface Engineering of Water-Dispersible Near-Infrared-Emitting CuInZnS/ZnSe/ZnS Quantum Dots.

We report the synthesis of near-infrared (IR)-emitting core/shell/shell quantum dots of CuInZnS/ZnSe/ZnS and their phase transfer to water. The intermediate ZnSe shell was added to inhibit the migration of ions from the standard ZnS shell into the emitting core, which often leads to a blue shift in the emission profile. By engineering the interface between the core and terminal shell layer, the optical properties can be controlled, and emission was maintained in the near-IR region, making the materials attractive for biological applications. In addition, the hydrodynamic diameter of the particle was controlled using amphiphilic polymers.

Profiling alveolar macrophage responses to inhaled compounds using in vitro high content image analysis.

One of the main hurdles in the development of new inhaled medicines is the frequent observation of foamy macrophage (FM) responses in non-clinical studies in experimental animals, which raises safety concerns and hinders progress into clinical trials. We have investigated the potential of a novel multi-parameter high content image analysis (HCIA) assay as an in vitro safety screening tool to predict drug induced FM. Rat (NR8383) and human U937-derived alveolar macrophages were exposed in vitro to a panel of model compounds with different biological activity, including inhaled bronchodilators, inhaled corticosteroids (ICS), phospholipidosis inducers and proapoptotic agents. An HCIA was utilized to produce drug-induced cell response profiles based on individual cell health, morphology and lipid content parameters. The profiles of both rat and human macrophage cell lines differentiated between cell responses to marketed inhaled drugs and compounds known to induce phospholipidosis and apoptosis. Hierarchical clustering of the aggregated data allowed identification of distinct cell profiles in response to exposure to phospholipidosis and apoptosis inducers. Additionally, in NR8383 cell responses formed two distinct clusters, associated with increased vacuolation with or without lipid accumulation. U937 cells presented a similar trend but appeared less sensitive to drug exposure and presented a narrower range of responses. These results indicate that our multi-parameter HCIA assay is suitable to generate characteristic drug-induced macrophage response profiles, thus enabling differentiation of foamy macrophage phenotypes associated with phospholipidosis and apoptosis. This approach shows great potential as pre-clinical in vitro screening tool for safety assessment of candidate inhaled medicines.

Atrofia multisistémica del tipo cerebelosa: implicaciones patológicas de la conectividad neuronal / Multiple system atrophy cerebellar variant: pathological implica-tions of the neural connectivity

Introducción. La atrofia multisistémica (MSA) es una enfermedad neurodegenerativa progresiva que afecta principal-mente la materia blanca (WM, por su sigla en inglés). Este tipo de atrofia se caracteriza por ocasionar inclusiones cito-plasmáticas gliales de la proteína alfa-sinucleína, además de disminuir la integridad, la desmielinización y los cambios en los diámetros axonales de la WM (trastornos del movimiento). Objetivo. Evaluar los hallazgos patológicos de la conectividad encontrados en casos de atrofia multisistémica de tipo cerebelosa (MSA-C) y las posibles conexiones que estos muestran con las señales clínicas, la fisiopatología de la enferme-dad, la imagenología y los blancos terapéuticos mediante una revisión sistemática de la literatura científica disponible. Métodos. Se realizó una búsqueda bibliográfica en las bases de datos PubMed, ResearchGate, Embase y Scopus con los siguientes términos claves: "Multiple system atrophy" AND "therapy" OR "diagnostic imagining" OR "physiopa-thology" OR epidemiology". Se seleccionaron artículos, en español e inglés, publicados entre 1989 y 2022. Tras aplicar los criterios de inclusión y exclusión y eliminar duplicados, se seleccionaron 61 estudios que comparaban los temas objetivo del estudio. Resultados. La conectividad funcional disminuida en la red de control ejecutivo izquierdo (ECN), relacionada con los circuitos de los ganglios basales y el tálamo, ocasiona desconexión cerebelo-prefrontal y cerebelo-amigdaloide / parahipocampal, lo cual tiene manifestaciones neuro histopatológicas que están correlacionadas con ciertos hallazgos imagenológicos. Conclusión. Se evidenció que resultados de diversos estudios han permitido dar viabilidad a la comprensión de la co-nectividad nodal identificada y sus manifestaciones anatomo-patológicas y funcionales en el curso natural de la MSA-C.

Introduction. Multiple system atrophy (MSA) is a progressive neurodegenerative disease primarily affecting white mat-ter (WM). This type of atrophy is characterized by causing glial cytoplasmic inclusions of the alpha-synuclein protein and decreasing the integrity, demyelination, and changes in the axonal diameter (movement disorders). Objective. To evaluate the pathological findings of connectivity found in cases of Multiple system atrophy-cerebellar subtype (MSA-C) and the possible connections that these show with clinical signs, the pathophysiology of the disease, imaging and therapeutic targets through a systematic review of the available scientific literature. Methods. A bibliographic search was carried out in the PubMed, ResearchGate, Embase, and Scopus databases with the following key terms: "Multiple system atrophy" AND "therapy" OR "diagnostic imagining" OR "physiopathology" OR "epidemiology." Articles were selected in Spanish and English and published between 1989 and 2022. After apply-ing the inclusion and exclusion criteria and eliminating duplicates, 61 studies were selected that compared the study's target topics. Results. Decreased functional connectivity in the left executive control network (ECN), related to the circuits of the basal ganglia and thalamus, causes cerebellar-prefrontal and cerebellar-amygdaloid/parahippocampal disconnection, which has neuro histopathological manifestations that are correlated with specific imaging findings. Conclusion. It was evident that the results of various studies have made it possible to give viability to the understanding of the identified nodal connectivity and its anatomical-pathological and functional manifestations in the natural course of MSA-C.

Photosensitized and Photothermal Stimulation of Cellular Membranes by Organic Thin Films and Nanoparticles.

Conjugated polymers are increasingly exploited for biomedical applications. In this work, we explored the optical characteristics of conjugated polymers of variable chemical structures at multiple levels relevant to biological interfacing, from fluorescence yield to their influence on cellular membrane potential. We systematically compared the performance of conjugated polymer as cast thin films and as nanoparticles stabilized with amphiphilic polyethylene glycol-poly lactic acid-co-glycolic acid (PEG-PLGA). We assessed in both the dark and under illumination the stability of key optoelectronic properties in various environments, including air and biologically relevant physiological saline solutions. We found that photoreduction of oxygen correlates with nanoparticle and film degradation in physiologically relevant media. Using patch-clamp recordings in cell lines and primary neurons, we identified two broad classes of membrane potential response, which correspond to photosensitizer- and photothermal-mediated effects. Last, we introduced a metric named OED50 (optical energy for 50% depolarization), which conveys the phototoxic potency of a given agent and thereby its operational photo-safety profile.

Theranostic Near-Infrared-Active Conjugated Polymer Nanoparticles.

Conjugated polymer nanoparticles (CPNs) based on a common solar cell material (PTB7) have been prepared, and their potential in theranostic applications based on bioimaging and photosensitizing capabilities has been evaluated. The main absorption and emission bands of the prepared CPNs both fell within the NIR-I (650-950 nm) transparency window, allowing facile and efficient implementation of our CPNs as bioimaging agents, as demonstrated in this work for A549 human lung cancer cell cultures. The prepared CPN samples were also shown to produce reactive oxygen species (ROS) upon photoexcitation in the near-infrared or ultraviolet spectral regions, both in aqueous solutions and in HaCaT keratinocyte cell cultures. Importantly, we show that the photosensitizing ability of our CPNs was largely determined by the nature of the stabilizing shell: coating the CPNs with a Pluronic F-127 copolymer led to an improvement of photoinitiated ROS production, while using poly[styrene-co-maleic anhydride] instead completely quenched said process. This work therefore demonstrates that the photosensitizing capability of CPNs can be modulated via an appropriate selection of stabilizing material and highlights the significance of this parameter for the on-demand design of theranostic probes based on CPNs.

Abortion as a human right: The struggle to implement the abortion law in Colombia.

In 2006, a Colombian Constitutional Court decision legalized abortion in cases of risk to a woman's physical or mental health, fetal malformation incompatible with life, or rape or incest. This decision resulted from legal action brought by feminist groups, and frames abortion as a human right. Advocates played a key role in implementing the new law by educating providers and the public about its broad interpretations. Healthcare providers and facilities did not have an organized response to the new law. Nonprofit organizations filled this gap, and provide a majority of legal abortions throughout the country. Civil society facilitated implementation of the new law by providing legal accompaniment to women facing barriers to accessing abortions. Despite these efforts, few legal abortions are performed each year, and clandestine, often unsafe abortions continue to prevail. Lack of information about the new law, stigma, and fluctuating political will remain key barriers.

Influence of the Surfactant Structure on Photoluminescent π-Conjugated Polymer Nanoparticles: Interfacial Properties and Protein Binding.

π-Conjugated polymer nanoparticles (CPNs) are under investigation as photoluminescent agents for diagnostics and bioimaging. To determine whether the choice of surfactant can improve CPN properties and prevent protein adsorption, five nonionic polyethylene glycol alkyl ether surfactants were used to produce CPNs from three representative π-conjugated polymers. The surfactant structure did not influence size or yield, which was dependent on the nature of the conjugated polymer. Hydrophobic interaction chromatography, contact angle, quartz crystal microbalance, and neutron reflectivity studies were used to assess the affinity of the surfactant to the conjugated polymer surface and indicated that all surfactants were displaced by the addition of a model serum protein. In summary, CPN preparation methods which rely on surface coating of a conjugated polymer core with amphiphilic surfactants may produce systems with good yields and colloidal stability in vitro, but may be susceptible to significant surface alterations in physiological fluids.

Post-polymerization C-H Borylation of Donor-Acceptor Materials Gives Highly Efficient Solid State Near-Infrared Emitters for Near-IR-OLEDs and Effective Biological Imaging.

Post-polymerization modification of the donor-acceptor polymer, poly(9,9-dioctylfluorene-alt-benzothiadiazole), PF8-BT, by electrophilic C-H borylation is a simple method to introduce controllable quantities of near-infrared (near-IR) emitting chromophore units into the backbone of a conjugated polymer. The highly stable borylated unit possesses a significantly lower LUMO energy than the pristine polymer resulting in a reduction in the band gap of the polymer by up to 0.63 eV and a red shift in emission of more than 150 nm. Extensively borylated polymers absorb strongly in the deep red/near-IR and are highly emissive in the near-IR region of the spectrum in solution and solid state. Photoluminescence quantum yield (PLQY) values are extremely high in the solid state for materials with emission maxima ≥ 700 nm with PLQY values of 44% at 700 nm and 11% at 757 nm for PF8-BT with different borylation levels. This high brightness enables efficient solution processed near-IR emitting OLEDs to be fabricated and highly emissive borylated polymer loaded conjugated polymer nanoparticles (CPNPs) to be prepared. The latter are bright, photostable, low toxicity bioimaging agents that in phantom mouse studies show higher signal to background ratios for emission at 820 nm than the ubiquitous near-IR emissive bioimaging agent indocyanine green. This methodology represents a general approach for the post-polymerization functionalization of donor-acceptor polymers to reduce the band gap as confirmed by the C-H borylation of poly((9,9-dioctylfluorene)-2,7-diyl-alt-[4,7-bis(3-hexylthien-5-yl)-2,1,3-benzothiadiazole]-2c,2cc-diyl) (PF8TBT) resulting in a red shift in emission of >150 nm, thereby shifting the emission maximum to 810 nm.

Development of a Conceptual Model and Survey Instrument to Measure Conscientious Objection to Abortion Provision.

BACKGROUND AND OBJECTIVE: Conscientious objection to abortion, clinicians' refusal to perform legal abortions because of their religious or moral beliefs, has been the subject of increasing debate among bioethicists, policymakers, and public health advocates in recent years. Conscientious objection policies are intended to balance reproductive rights and clinicians' beliefs. However, in practice, clinician objection can act as a barrier to abortion access-impinging on reproductive rights, and increasing unsafe abortion and related morbidity and mortality. There is little information about conscientious objection from a medical or public health perspective. A quantitative instrument is needed to assess prevalence of conscientious objection and to provide insight on its practice. This paper describes the development of a survey instrument to measure conscientious objection to abortion provision. METHODS: A literature review, and in-depth formative interviews with stakeholders in Colombia were used to develop a conceptual model of conscientious objection. This model led to the development of a survey, which was piloted, and then administered, in Ghana. RESULTS: The model posits three domains of conscientious objection that form the basis for the survey instrument: 1) beliefs about abortion and conscientious objection; 2) actions related to conscientious objection and abortion; and 3) self-identification as a conscientious objector. CONCLUSIONS: The instrument is intended to be used to assess prevalence among clinicians trained to provide abortions, and to gain insight on how conscientious objection is practiced in a variety of settings. Its results can inform more effective and appropriate strategies to regulate conscientious objection.

Data from two different culture conditions of Thalassiosira weissflogii diatom and from cleaning procedures for obtaining monodisperse nanostructured biosilica.

Diatoms microalgae produce biosilica nanoporous rigid outershells called frustules that exhibit an intricate nanostructured pore pattern. In this paper two specific Thalassiosira weissflogii culture conditions and size control procedures during the diatoms growth are described. Data from white field and fluorescence microscopy, evaluation of cell densities and cell parameters (k value and R value) according to cell culture conditions are listed. Different cleaning procedures for obtaining bare frustules are described. In addition, FTIR and spectrofluorimetric analyses of cleaned biosilica are shown. The data are related to the research article "Chemically Modified Diatoms Biosilica for Bone Cell Growth with Combined Drug-Delivery and Antioxidant Properties" [1].

Bases genéticas y moleculares de la preeclampsia / Genetic and molecular bases of preeclampsia

La preeclampsia es una enfermedad compleja, exclusiva de la gestación humana y responsable de una alta morbimortalidad perinatal. Ha sido denominada la enfermedad de las múltiples teorías, en la cual tanto factores medioambientales como genéticos se han asociado al desarrollo de la misma. Para la identificación de los genes candidatos asociados con la PE, se han empleado dos tipos de metodología, los estudios de asociación y los estudios de ligamiento. En el presente artículo se explica el fundamento de ambos estudios y se revisan los principales genes candidatos dentro de la fisiopatología de la enfermedad, entre los que se encuentran los que codifican para las enzimas metileneterahidrofolato reductasa, la lipoprotein lipasa y la óxido nítrico sintasa endotelial; el factor V de Leiden, el angiotensinógeno, el HLA-G y el factor de necrosis tumoral alfa