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Aim: Feminizing genital gender affirmation surgery (fgGAS) is increasing in prevalence in the USA. Management of postoperative pain following fgGAS is challenging. We report a series of patients where post-fgGAS pain was adequately controlled with paraspinal blocks. Materials & methods: This is a case series of three patients who received bilateral lumbar and sacral erector spinae plane blocks after fgGAS. Block techniques, medications administered, opioid requirements and pain scores were reviewed. Results: Erector spinae plane blocks provided adequate analgesia for 24–48 h following the block. Conclusion: Currently, there are two regional anesthetic techniques described for the treatment of postoperative pain after fgGAS. We describe two additional approaches as options for improved pain management in this patient population.

Pregnant women and new mothers are among the most vulnerable to seasonal influenza; however, little is known about their preferences for flu vaccination. We examined the rural-urban differences in uptake, demand and willingness to pay (WTP) for influenza vaccination among women of childbearing age, to assess the feasibility of implementing locally produced vaccines in Vietnam.A cross-sectional study was performed in both urban and rural areas of Hanoi in 2018. Socio-demographic characteristics, history of vaccination, demand and WTP for influenza vaccines were obtained. A multivariate logistic regression model was employed to identify the associated factors.Of 750 participants, 29.9% had had flu shots in the current or previous flu season and 64.3% indicated demand for this vaccine. The median of the maximum amount of WTP for influenza vaccination services was US$ 8.5 (IQR: 8.5-17.0). Women living in rural areas had a significantly lower uptake and higher demand, and were willing to pay less than women in urban locations (21.1% vs. 36.6%; 69% vs. 60.2%; and US $8.5 vs. US $11.7, respectively). For urban participants, factors associated with higher demand and WTP for flu shots included having ANC in health facilities and having been vaccinated against influenza in the past; for rural women, these factors were having suffered from influenza and hearing about it.This study informs the feasibility of implementing locally produced influenza vaccines in Vietnam. Educational programs, along with counselling services and government subsidies, should be implemented to improve the coverage, demand and WTP for the vaccine.Les femmes enceintes et les nouvelles mères sont parmi les plus vulnérables à la grippe saisonnière; cependant, on en sait peu sur leurs préférences pour la vaccination contre la grippe. Nous avons examiné les différences entre les zones rurales et urbaines dans l'adoption, la demande et la volonté de payer pour la vaccination antigrippale chez les femmes en âge de procréer, afin d'évaluer la faisabilité de la mise en œuvre de vaccins produits localement au Vietnam. MÉTHODES: Une étude transversale a été réalisée dans les zones urbaines et rurales de Hanoi en 2018. Les caractéristiques sociodémographiques, les antécédents de vaccination, la demande et la volonté de payer pour les vaccins antigrippaux ont été obtenus. Un modèle de régression logistique multivariée a été utilisé pour identifier les facteurs associés. RÉSULTATS: Sur 750 participantes, 29,9% s'étaient fait vacciner contre la grippe au cours de la saison grippale actuelle ou précédente, 64,3% ont indiqué une demande pour ce vaccin. La médiane du montant maximal de la volonté de payer pour les services de vaccination contre la grippe était de 8,5 USD (IQR: 8,5 à 17,0). Les femmes vivant dans les zones rurales avaient une adoption nettement plus faible, une demande plus élevée et étaient prêtes à payer moins que les femmes des zones urbaines (21,1% contre 36,6%; 69% contre 60,2%; et 8,5 USD contre 11,7 USD, respectivement). Pour les participantes urbaines, les facteurs associés à une demande plus élevée et à la volonté de payer pour les vaccins contre la grippe comprenaient le fait d'avoir des soins prénatals dans les établissements de santé et d'avoir été vaccinés contre la grippe dans le passé; pour les femmes rurales, ces facteurs comprenaient, avoir souffert de la grippe et en avoir entendu parler.Cette étude informe sur la faisabilité de la mise en œuvre de vaccins antigrippaux produits localement au Vietnam. Des programmes éducatifs, ainsi que des services de conseil et des subventions gouvernementales devraient être mis en œuvre pour améliorer la couverture, la demande et la volonté de payer pour le vaccin.

Breast cancer cells release a large quantity of biocargo-bearing extracellular vesicles (EVs), which mediate intercellular communication within the tumour microenvironment and promote metastasis. To identify EV-bound proteins related to metastasis, we used mass spectrometry to profile EVs from highly and poorly metastatic breast cancer lines of human and mouse origins. Comparative mass spectrometry indicated that integrins, including αv and β1 subunits, are preferentially enriched in EVs of highly metastatic origin over those of poorly metastatic origin. These results are consistent with our histopathological findings, which show that integrin αv is associated with disease progression in breast cancer patients. Integrin αv colocalizes with the multivesicular-body marker CD63 at a higher frequency in the tumour and is enriched in circulating EVs of breast cancer patients at late stages when compared with circulating EVs from early-stage patients. With a magnetic bead-based flow cytometry assay, we confirmed that integrins αv and β1 are enriched in the CD63

Despite significant eradication efforts, malaria remains a persistent infectious disease with high mortality due to the lack of efficient point-of-care (PoC) screening solutions required to manage low-density asymptomatic parasitemia. In response, we demonstrate a quantitative electrical biosensor based on system-integrated two-dimensional field-effect transistors (2DBioFETs) of reduced graphene oxide (rGO) as transducer for high sensitivity screening of the main malaria biomarker, Plasmodium falciparum lactate dehydrogenase (PfLDH). The 2DBioFETs were biofunctionalized with pyrene-modified 2008s aptamers as specific PfLDH receptors. While we systematically optimize biosensor interface for optimal performance, aptamer-protein transduction at 2DBioFETs is elucidated based on delineation of charge and capacitance in an updated analytical model for two-dimensional rGO/biofunctional layer/electrolyte (2DiBLE) interfaces. Our 2DBioFET-aptasensors display a limit-of-detection down to 0.78 fM (0.11 pg/mL), dynamic ranges over 9 orders of magnitude (subfemto to submicromolar), high sensitivity, and selectivity in human serum validating their diagnostic potential as rapid PoC tests for malarial management.

Introduction: Blood group antigens are defined by an immune response that generates antibodies against a red blood cell molecule. Antibodies against these antigens can be associated with haemolytic...

The novel Coronavirus-2019 (COVID-19) was declared a pandemic by the World Health Organization (WHO) in March 2020, impacting the lifestyles, economy, physical and mental health of individuals globally. This study aimed to test the model triggered by physical symptoms resembling COVID-19 infection, in which the need for health information and perceived impact of the pandemic mediated the path sequentially, leading to adverse mental health outcomes. A cross-sectional research design with chain mediation model involving 4612 participants from participating 8 countries selected via a respondent-driven sampling strategy was used. Participants completed online questionnaires on physical symptoms, the need for health information, the Impact of Event Scale-Revised (IES-R) questionnaire and Depression, Anxiety and Stress Scale (DASS-21). The results showed that Poland and the Philippines were the two countries with the highest levels of anxiety, depression and stress; conversely, Vietnam had the lowest mean scores in these areas. Chain mediation model showed the need for health information, and the perceived impact of the pandemic were sequential mediators between physical symptoms resembling COVID-19 infection (predictor) and consequent mental health status (outcome). Excessive and contradictory health information might increase the perceived impact of the pandemic. Rapid COVID-19 testing should be implemented to minimize the psychological burden associated with physical symptoms, whilst public mental health interventions could target adverse mental outcomes associated with the pandemic.

Study objective In the initial description of the serratus anterior plane block (SAPB), both superficial and deep SAPB provided effective blockade. The purpose of this study was to investigate the difference in opioid consumption and postoperative analgesia between superficial and deep SAPB for patients undergoing mastectomy. Design Randomized prospective trial. Setting Academic hospital. Patients 64 women, >18 years of age, ASA I-III, undergoing single or bilateral mastectomy, with and without lymph node biopsy, with and without tissue expander reconstruction. Intervention Either superficial or deep SAPB by an ultrasound-guided technique in addition to multimodal analgesia. Measurements The primary outcome was opioid consumption in the first 24 h. Secondary outcomes were pain scores, satisfaction scores, incidence of PONV, length of stay and block performance time. Results Subjects who received a deep SAPB required 30% less oral morphine equivalents (OME) (113.5 mg vs. 147 mg, p = 0.009) and reported lower pain scores. There were no significant differences in satisfaction scores, incidence of PONV, LOS, or block performance time between the two groups. Conclusion There was a significant difference in opioid consumption between the deep and superficial SAPB groups. Subjects in the deep SAPB group had lower pain scores at 12 h; however, the difference was not statistically significant at other time points. While both the superficial and the deep SAPB can be used for post-operative analgesia in patients undergoing mastectomy, our study suggests that the deep SAPB may improve analgesia to a greater degree than the superficial SAPB as shown through decreased opioid consumption of 30% over a 24-h period post-block. Clinical trial number and registry URL clinicaltrials.gov : NCT03154658

A metabolic imbalance between lipid synthesis and degradation can lead to hepatic lipid accumulation, a characteristic of patients with non-alcoholic fatty liver disease (NAFLD). Here, we report that high-fat-diet-induced sterol regulatory element-binding protein (SREBP)-1c, a key transcription factor that regulates lipid biosynthesis, impairs autophagic lipid catabolism via altered H2S signaling. SREBP-1c reduced cystathionine gamma-lyase (CSE) via miR-216a, which in turn decreased hepatic H2S levels and sulfhydration-dependent activation of Unc-51-like autophagy-activating kinase 1 (ULK1). Furthermore, Cys951Ser mutation of ULK1 decreased autolysosome formation and promoted hepatic lipid accumulation in mice, suggesting that the loss of ULK1 sulfhydration was directly associated with the pathogenesis of NAFLD. Moreover, silencing of CSE in SREBP-1c knockout mice increased liver triglycerides, confirming the connection between CSE, autophagy, and SREBP-1c. Overall, our results uncover a 2-fold mechanism for SREBP-1c-driven hepatic lipid accumulation through reciprocal activation and inhibition of hepatic lipid biosynthesis and degradation, respectively.

Despite the recent advances in drug development, the majority of novel therapeutics have not been successfully translated into clinical applications. One of the major factors hindering their clinical translation is the lack of a safe, non-immunogenic delivery system with high target specificity upon systemic administration. In this respect, extracellular vesicles (EVs), as natural carriers of bioactive cargo, have emerged as a promising solution and can be further modified to improve their therapeutic efficacy. In this review, we provide an overview of the biogenesis pathways, biochemical features, and isolation methods of EVs with an emphasis on their many intrinsic properties that make them desirable as drug carriers. We then describe in detail the current advances in EV therapeutics, focusing on how EVs can be engineered to achieve improved target specificity, better circulation kinetics, and efficient encapsulation of therapeutic payloads. We also identify the challenges and obstacles ahead for clinical translation and provide an outlook on the future perspective of EV-based therapeutics.

The cellular prion protein (PrPC), mainly known for its role in neurodegenerative diseases, is involved in several physiological processes including neuritogenesis. In addition, its ability to bind copper or zinc has been suggested for its role in metal homeostasis. Although PrPC has been known as a copper-binding molecule, little is known about how copper can affect PrPC physiological functions. By combining genomic approaches, cellular assays, and focal stimulation technique, we found that PrPC neuritogenesis function is directly influenced by N-terminal copper-binding amino acids. Several recombinant mouse PrP (recMoPrP) mutants at N-terminal copper-binding sites were produced, and primary hippocampal cultures were treated either in bulk or exposed near the hippocampal growth cones (GC) of single neurons in local stimulation manner. While focal stimulation of GC with wild-type recMoPrP induced neurite outgrowth and rapid GC turning toward the source, N-terminal mutants fail to support this effect. Indeed, disrupting all the copper-binding sites at the N-terminus of PrPC was toxic to neurons indicating that these regions are crucial for the protein function. Mutants at both octarepeat and non-octarepeat region abolished the neuritogenesis effect. Altogether, our findings indicate the crucial role of copper-binding sites in maintaining the neuritogenesis function in PrP, suggesting a potential link between loss-of-function of the protein and disease initiation.

BACKGROUND/AIM Studies reveal many dental students and general dentists have inadequate knowledge about treating children who sustain traumatic dental injuries. The aims of this study were to assess dental trauma knowledge among novice clinicians and expert pediatric dentists and determine the effectiveness of a clinical decision support tool (CDST) for the management of trauma scenarios. A secondary purpose was to compare the effects of a print and mobile app format of the CDST. METHODS A print and mobile app CDST was developed based upon current AAPD and IADT clinical guidelines. Baseline knowledge for dental students (n = 84) and pediatric dentists (n = 60) was assessed using a multiple-choice Pre-test. A Post-test was used to evaluate changes in the knowledge level following the random assignment of participants into 3 groups: Group A (control) had no CDST provided; Group B (print CDST) had access to the print paper pamphlet; and Group C (mobile app CDST) had access to the mobile app on a handheld device for use during the Post-test. Test scores and time required to complete each test were recorded. RESULTS Pediatric dentists scored significantly higher and required less time on both the Pre-test (P

Protein and polysaccharide mixed systems have been actively studied for at least 50years as they can be assembled into functional particles or gels. This article reviews the properties of electrostatic gels, a recently discovered particular case of associative protein-polysaccharide mixtures formed through associative electrostatic interaction under appropriate solution conditions (coupled gel). This review highlights the factors influencing gel formation such as protein-polysaccharide ratio, biopolymer structural characteristics, final pH, ionic strength and total solid concentration. For the first time, the functional properties of protein-polysaccharide coupled gels are presented and discussed in relationship to individual protein and polysaccharide hydrogels. One of their outstanding characteristics is their gel water retention. Up to 600g of water per g of biopolymer may be retained in the electrostatic gel network compared to a protein gel (3-9g of water per g of protein). Potential applications of the gels are proposed to enable the food and non-food industries to develop new functional products with desirable attributes or new interesting materials to incorporate bioactive molecules.

Despite the critical role of melanin in the protection of skin against UV radiation, excess production of melanin can lead to hyperpigmentation and skin cancer. Pear fruits are often used in traditional medicine for the treatment of melasma; therefore, we investigated the effects of pear extract (PE) and its component, protocatechuic acid (PCA), on melanogenesis in mouse melanoma cells. We found that PE and PCA significantly suppressed melanin content and cellular tyrosinase activity through a decrease in the expression of melanogenic enzymes and microphthalmia-associated transcription factor (Mitf) in α-melanocyte stimulating hormone-stimulated mouse melanoma cells. Moreover, PCA decreased cyclic adenosine monophosphate (cAMP) levels and cAMP-responsive element-binding protein phosphorylation, which downregulated Mitf promoter activation and subsequently mediated the inhibition of melanogenesis. These results suggested that pear may be an effective skin lightening agent that targets either a tyrosinase activity or a melanogenic pathway.

INTRODUCTION: Transitioning from an associate degree to a baccalaureate degree for respiratory therapists has been suggested as a new entry-level educational standard. One potential risk for this change is that it may limit the diversity of potential applicants for entry-level education. A diverse workforce is important to achieve the goal of reducing healthcare disparities. This study evaluated characteristics of therapists who completed associate and baccalaureate degree entry-level education. METHODS: A secondary analysis of data collected from the 2009 AARC Respiratory Therapist Human Resource Survey explored relationships between the choice of entry-level associate or baccalaureate education and variables of gender, race, salary, career advancement, and job satisfaction. RESULTS: There were no differences between therapists with entry-level associate and baccalaureate degrees in gender, race, number of additional healthcare credentials, numbers of life support credentials, wages, delivering respiratory care by protocol, and job satisfaction. There were significantly higher percentages of advanced academic degrees, desire to pursue a higher academic degree, registered respiratory therapist credentials, total National Board for Respiratory Care credentials, and leadership roles for therapists with baccalaureate entry-level degrees. CONCLUSIONS: Current entry-level associate and baccalaureate degree graduates have similar gender and race proportions. This finding challenges concerns that an entry-level baccalaureate degree would decrease the diversity of the respiratory therapist workforce.

To investigate cyanoacrylate tissue adhesives in ulcerative keratitis. They represent one of the best emergency treatments of corneal descemetoceles, preperforated corneal ulcers, impending corneal perforations and small corneal perforations.Nine patients presenting with peripheral ulcerative keratitis were treated by this method between 1990 and 1994. The underlying diseases included Mooren's ulcer (5 eyes), rosacea (2 eyes) and rheumatoid arthritis (2 eyes).Despite the poor prognosis of ulcerative keratitis, good healing and corneal re-epithelialization were obtained in 6 cases (66%) without any relapse. Severe infectious complications occurred in 1 case (11%) and required a therapeutic penetrating keratoplasty.Cyanoacrylate tissue adhesives are an effective and well tolerated treatment of peripheral ulcerative keratitis associated with ocular inflammatory diseases. Potential infectious complications impose a strict follow-up.

Ocular surface diseases (OSD) affect about 15% of the population over 65 years of age. Nevertheless, OSD knowledge in the scientific community remains poor, and the healthcare system does not adequately recognize this disorder. However, many patients with OSD suffering from chronic pain experience substantial alteration in their quality of life (QoL).Our work aimed at developing a patient self-evaluation questionnaire specific to OSD. This questionnaire could thus become a useful diagnostic tool that ophthalmologists could employ in daily practice in order to better understand patients'complaints and thereby correctly treat their disease. It also may serve as an evaluation tool in medical research. This article describes the phases of item generation, validation by experts, and identification of dimensions in the QoL section.The questionnaire was developed in French by a group of experts including clinicians and methodologists. It comprised two parts: one on diagnostic aid, and the other on subjective perception of the disease (symptoms, perception of treatment, quality of life). The questionnaire was tested on five patients. It was then modified according to the patients' suggestions and tested again on 20 patients. After a second review by the scientific committee, a pilot questionnaire suitable for systematic use in quantitative studies was prepared. A cross-sectional observational study then identified the statistical dimensions of the QoL section, which led to a reduction in the total number of items.The resulting operational version of the questionnaire included four sectionsThe next study will test the reproducibility of the operational version of the OSD questionnaire obtained after the item reduction phase.