Histopathology of the Tongue in a Hamster Model of COVID-19.

Objective: With altered sense of taste being a common symptom of coronavirus disease 2019 (COVID-19), our objective was to investigate the presence and distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) within the tongue over the course of infection. Methods: Golden Syrian hamsters were inoculated intranasally with SARS-CoV-2 and tongues were collected at 2, 3, 5, 8, 17, 21, 35, and 42 days post-infection (dpi) for analysis. In order to test for gross changes in the tongue, the papillae of the tongue were counted. Paraffin-embedded thin sections of the tongues were labeled for the presence of SARS-CoV-2 antigen. Results: There was no difference in fungiform or filiform papillae density throughout the course of infection. SARS-CoV-2 antigen was observed in the circumvallate papillae taste buds (3-35 dpi) and autonomic ganglia (5-35 dpi), as well as in the serous and mucous salivary glands of the posterior tongue (2-42 dpi). Conclusion: The presence and distribution of SARS-CoV-2 suggest that the virus could cause taste disturbance by infecting the circumvallate taste buds. This effect could be exacerbated by a diminished secretion of saliva caused by infection of the serous salivary glands and the autonomic ganglia which innervate them.

Polymeric Micellar Nanoparticles Enable Image-guided Drug Delivery in Solid Tumors.

We report the development of a nanotechnology to co-deliver chemocoxib A with a reactive oxygen species (ROS)-activatable and COX-2 targeted pro-fluorescent probe, fluorocoxib Q (FQ) enabling real time visualization of COX-2 and CA drug delivery into solid cancers, using a di-block PPS 135 - b -POEGA 17 copolymer, selected for its intrinsic responsiveness to elevated reactive oxygen species (ROS), a key trait of the tumor microenvironment. FQ and CA were synthesized independently, then co-encapsulated within micellar PPS 135 - b -POEGA 17 co-polymeric nanoparticles (FQ-CA-NPs), and were assessed for cargo concentration, hydrodynamic diameter, zeta potential, and ROS-dependent cargo release. The uptake of FQ-CA-NPs in mouse mammary cancer cells and cargo release was assessed by fluorescence microscopy. Intravenous delivery of FQ-CA-NPs to mice harboring orthotopic mammary tumors, followed by vital optimal imaging, was used to assess delivery to tumors in vivo . The CA-FQ-NPs exhibited a hydrodynamic diameter of 109.2 ± 4.1 nm and a zeta potential (σ) of -1.59 ± 0.3 mV. Fluorescence microscopy showed ROS-dependent cargo release by FQ-CA-NPs in 4T1 cells, decreasing growth of 4T1 breast cancer cells, but not affecting growth of primary human mammary epithelial cells (HMECs). NP-derived fluorescence was detected in mammary tumors, but not in healthy organs. Tumor LC-MS/MS analysis identified both CA (2.38 nmol/g tumor tissue) and FQ (0.115 nmol/g tumor tissue), confirming the FQ-mediated image guidance of CA delivery in solid tumors. Thus, co-encapsulation of FQ and CA into micellar nanoparticles (FQ-CA-NPs) enabled ROS-sensitive drug release and COX-2-targeted visualization of solid tumors.

Dietary Intakes of Long-Chain Polyunsaturated Fatty Acids and Impulsivity: Comparing Non-Restricted, Vegetarian, and Vegan Diets.

BACKGROUND: Research suggests a link between deficiencies in omega-3 long-chain polyunsaturated fatty acids (LCPUFAs) and impulsivity among psychiatric populations. However, this association is less evident in non-clinical populations. As omega-3 LCPUFAs are predominantly sourced through fish consumption, non-fish dieters may be more vulnerable to higher impulsivity. METHODS: This cross-sectional observational study explored the association between lower intakes of omega-3 LCPUFA food sources and higher self-reported measures of impulsivity among healthy adults consuming non-restricted, vegetarian, and vegan diets. RESULTS: The results from the validated Food Frequency Questionnaire showed significantly lower estimated omega-3 LCPUFA intakes among vegans and vegetarians when compared with people consuming non-restricted diets. Furthermore, although all groups scored within the normal range of impulsivity measures, vegans scored comparatively higher. Vegans also scored significantly higher in impulsivity control relating to attention than those consuming non-restricted diets. CONCLUSIONS: The significantly lower omega-3 LCPUFA dietary intakes in the vegan diets were associated with higher scores in the second-order attentional aspect of self-reported impulsiveness.

Structural optimization of siRNA conjugates for albumin binding achieves effective MCL1-directed cancer therapy.

The high potential of siRNAs to silence oncogenic drivers remains largely untapped due to the challenges of tumor cell delivery. Here, divalent lipid-conjugated siRNAs are optimized for in situ binding to albumin to improve pharmacokinetics and tumor delivery. Systematic variation of the siRNA conjugate structure reveals that the location of the linker branching site dictates tendency toward albumin association versus self-assembly, while the lipid hydrophobicity and reversibility of albumin binding also contribute to siRNA intracellular delivery. The lead structure increases tumor siRNA accumulation 12-fold in orthotopic triple negative breast cancer (TNBC) tumors over the parent siRNA. This structure achieves approximately 80% silencing of the anti-apoptotic oncogene MCL1 and yields better survival outcomes in three TNBC models than an MCL-1 small molecule inhibitor. These studies provide new structure-function insights on siRNA-lipid conjugate structures that are intravenously injected, associate in situ with serum albumin, and improve pharmacokinetics and tumor treatment efficacy.

Novel sensor-integrated proteome on chip (SPOC) platform with thousands of folded proteins on a 1.5 sq-cm biosensor chip to enable high-throughput real-time label-free screening for kinetic analysis.

An automated proteomic platform for producing and screening an array of functional proteins on biosensor surfaces was developed to address the challenges of measuring proteomic interaction kinetics in high throughput (HTP). This technology is termed Sensor-Integrated Proteome On Chip (SPOC®) which involves in-situ cell-free protein expression in nano-liter volume wells (nanowells) directly from rapidly customizable arrays of plasmid DNA, facilitating simultaneous capture-purification of up to 2400 unique full-length folded proteins onto a 1.5 sq-cm surface of a single gold biosensor chip. Arrayed SPOC sensors can then be screened by real-time label-free analysis, including surface plasmon resonance (SPR) to generate kinetic affinity, avidity data. Fluorescent and SPR assays were used to demonstrate zero crosstalk between protein spots. The functionality of the SPOC protein array was validated by antibody binding assay, post-translational modification, mutation-mediated differential binding kinetics, and catalytic activity screening on model SPOC protein arrays containing p53, Src, Jun, Fos, HIST1H3A, and SARS-CoV-2 receptor binding domain (RBD) protein variants of interest, among others. Monoclonal antibodies were found to selectively bind their target proteins on the SPOC array. A commercial anti-RBD antibody was used to demonstrate discriminatory binding to numerous SARS-CoV-2 RBD variants of concern with comprehensive kinetic information. With advantages of HTP, flexibility, low-cost, quick turnaround time, and real-time kinetic affinity profiling, the SPOC proteomic platform addresses the challenges of interrogating protein interactions at scale and can be deployed in various research and clinical applications.

Drugs without Doctors The Human Resource Challenges of Scaling Up Anti-Retroviral Therapy in High-Prevalence, Resource-Poor Settings

ART has the potential to transform the experience of living with HIV/AIDS in countries such as Mozambique with 1.4 million HIV-positive people, more than 300,000 of whom are presently in need of treatment. Since 2004, the Mozambican government, with the support of the international community, has been pursuing an ambitious plan to expand access to ART, yet there are 0.2 doctors and 2.8 nurses and midwives for every ten thousand people in the country. The aim of this report is to provide a situational analysis of present human resource constraints of expanding ART in Mozambique and critically discuss strategies and actors involved in facing the challenge. Methods A case study of HRH of ART delivery in Mozambique was conducted in order to analyse the present situation in relation to the human resource requirements of providing ART. This case study is interspersed with a selective literature review of HRH and ART in sub-Saharan Africa intended to provide a broader context for the findings. Findings Recent estimates of the human resource requirements of ART were related to HRH availability; in 2008, almost all of the doctors (82%), medical officers (96%) presently available in the country will be required to meet treatment goals. Without the inclusion of basic-level personnel, ART HR needs for pharmacy technicians (214%) greatly exceed availability. Several responses to the HRH crisis have been proposed, including increasing supply, task-shifting, and optimizing available health care workers; but an adequate response will require stronger commitment from international and national actors. Conclusions: HRH are one of the principle constraints on the expansion of ART Mozambique. Without a concerted effort and innovative solutions, ART will consume and in some cases exceed the available health workforce in the country. Responses to HR challenges depend on the international community, national and local authorities, and civil society.

Salud reproductiva y derechos humanos: Integración de la medicina, la ética y el derecho / Reproductive health and human rights: Integration of the medicine, the ethics and the right

Esta obra desarrolla la salud reproductiva de las mujeres desde el ámbito de los derechos humanos, al abordarla desde tres disciplinas que a juicio de los autores, deben integrarse: la medicina, la ética y el derecho

La santé des femmes et les droits de l'individu : la promotion et la protection de la santé des femmes par le droit international relatif aux droits de l' homme / Rebecca J. Cook / Women's health and human rights : the promotion and protection of women's health through international human rights law / La salud de la mujer y los derechos humanos : promoción y protección de la salud de la mujer en la legislación internacional sobre derechos humanos

Le droit des femmes à la santé est protégé par la législation internationale sur les droits individuels, et pourtant bien des Etats ne s'acquittent pas des obligations découlant des traités qu'ils ont signés. Il en résulte que beaucoup de femmes sont défavorisées sur le plan de la santé par rapport aux hommes. Le Professeur Rebacca Cook, juriste spécialisée dans les droits de l'homme, fait valoir que ces désavantages représentent une injustice au regard des accords relatifs aux droits de l'homme. L'auteur explique ce que les traités internationaux sur les droits de l'homme ont à dire au sujet des femmes, de la santé et de l'équité. Elle décrit comment les femmes sont plus vunérables que les hommes sur le plan de la santé. Elle tire des conclusions sur la façon dont les traités relatifs aux droits de l'homme pourraient être mis à profit pour améliorer la santé des femmes dans les pays qui les ont signés. Ce livre met les Etats et les gouvernements au défi de faire ce qu'ils se sont juridiquement engagés à accomplir, c'est-à-dire prendre toutes les mesures nécessaires pour assurer que les femmes soient pleinement à même de mener une vie saine et satisfaisante

La salud de la mujer y los derechos humanos: promocion y proteccion de la salud de la mujer en la legislación internacional sobre derechos humanos / Women's health and human rights: the promotion and protection of women's health through international human rights law

Aunque el derecho de las mujeres a la salud esta protegido por las leyes internacionales, sobre derechos humanos, a menudo los propios países signatarios dejan de cumplir con los tratados acordados. Como consecuencia, muchas mujeres sufren "desventajas de salud" en comparacion con los hombres. La autora, defensora de los derechos humanos, argumenta que estas desventajas representan una injusticia en relacion con los acuerdos sobre derechos humanos. Cook explica el alcance de los tratados acerca de la mujer, la salud y la equidad. Describe en que sentido las mujeres son mas propensas que los hombres a una salud quebrantada, y como los tratados sobre derechos humanos podrian usarse como un instrumento para mejorar la salud de la mujer en los países signatarios. Este libro desafia a estados y gobiernos a cumplir con lo que se comprometieron a hacer: dar los pasos necesarios para aseguar una vida saludable y plena para todas las mujeres

Women's health and human rights: the promotion and protection of women's health through international human rights law / Women's health and human rights: the promotion and protection of women's health through international human rights law

Women"s right to health is protected by international human rights law, yet States often fail to fulfil the obligations of the treaties they have signed. As a result, many women suffer "health disadvantages" compared with men. Human rights lawyer Professor Rebecca Cook argues that these disadvantages represent injustice in terms of human rights agreements

Professor Cook explains what international human rights treaties say about women, health and equity. She describes in what ways women are more liable to ill-health than are men. And she draws conclusions on how human rights treaties could be used as a lever to improve the health of women in the countries that have signed them

This book challenges States and Governments to do what they have legally bound themselves to do take all steps necessary to ensure that women are fully enabled to live healthy and fulfilling lives

La salud de la mujer y los derechos humanos: promoción y protección de la salud de la mujer en la legislación internacional sobre derechos humanos / Women's health and human rights: the promotion and protection of women's health through international human rights law

Aunque el derecho de las mujeres a la salud está protegido por las leyes internacionales, sobre derechos humanos, a menudo los propios países signatarios dejan de cumplir con los tratados acordados. Como consecuencia, muchas mujeres sufren "desventajas de salud" en comparación con los hombres. La autora, defensora de los derechos humanos, argumenta que estas desventajas representan una injusticia en relación con los acuerdos sobre derechos humanos

Cook explica el alcance de los tratados acerca de la mujer, la salud y la equidad. Describe en qué sentido las mujeres son más propensas que los hombres a una salud quebrantada, y cómo los tratados sobre derechos humanos podrían usarse como un instrumento para mejorar la salud de la mujer en los países signatarios

Este libro desafía a estados y gobiernos a cumplir con lo que se comprometieron a hacer: dar los pasos necesarios para aseguar una vida saludable y plena para todas las mujeres

La salud de la mujer y los derechos humanos: promoción y protección de la salud de la mujer en la legislación internacional sobre derechos humanos / Women's health and human rights: the promotion and protection of women's health trough International Human Rights Law

Contribución de la Organización Mundial de la Salud a la Conferencia Mundial sobre Derechos Humanos de 1993. Enfoca el tema de la salud de la mujer desde la óptica de la legislación internacional sobre derechos humanos. Ofrece una perspectiva jurídica acerca de la salud de la mujer, que difere de la que brindan los profesionales de la medicina, de la política y la paciente misma