7 ± 4.1 nm, with a PDI of 0.162 ± 0.037 and a zeta potential of +29.1 ± 2.4 mV. GUL-SS DTX/EZL-NPs showed high cancer cell uptake of about 70%, as well as higher cell growth inhibition efficiency (a maximum 79% of cells were inhibited after treatment) than single drug-loaded NPs and free drugs. GUL-SS DTX/EZL-NPs showed the most prominent tumor inhibition ability and less systemic toxicity. The novel GUL-SS DTX/EZL-NPs could be used as a promising system for PCa therapy.Sex workers in South Africa face numerous forms of stigmatisation. This stigma contributes to isolation from family – even if the sex worker financially supports family members – cruelty and verbal abuse from health workers, and violence at the hands of police, who often profile sex workers. Horribly, feelings of shame, can extend to the children of sex workers as well. Sex workers interviewed for a 2018 Human Rights Watch report 'Why Sex Work Should be Decriminalized in South Africa’ repeatedly expressed fear that their children would discover they did sex work, and that other people would treat their children badly because of their sex work. This creates a scenario where sex workers feel that, in order to love and care for their children, they have to hide their work. Supporting children is a main reason that marginalised people do sex work in South Africa but this fear prevents many sex workers from proudly joining advocacy efforts for decriminalisation. For this interview, the author of the 2018 report speaks with South African sex worker and advocate, Dudu Dlamini, who runs a project focused on mothers who are also sex workers, to learn more about the problem of self-advocacy for sex workers.

Aidi injection (ADI), a traditional Chinese medicine antitumor injection, is usually combined with doxorubicin (DOX) for the treatment of malignant tumours. The cardiotoxicity of DOX is ameliorated by ADI in the clinic. However, the relevant mechanism is unknown.

To investigate the effects of ADI on DOX-induced cardiotoxicity and its mechanism.

ICR mice were randomly divided into six groups control, ADI-L, ADI-H, DOX, DOX + ADI-L and DOX + ADI-H. DOX (

, 0.03 mg/10 g) was administered in the presence or absence of ADI (

0.1 or 0.2 mL/10 g) for two weeks. Heart pathology and levels of AST, LDH, CK, CK-MB and BNP were assessed. H9c2 cells were treated with DOX in the presence or absence of ADI (1, 4, 10%). Cell viability, caspase-3 activity, nuclear morphology, and CBR1 expression were then evaluated. DOX and doxorubicinol (DOXol) concentrations in heart, liver, kidneys, serum, and cells were analysed by UPLC-MS/MS.

High-dose ADI significantly reduced DOX-induced pathological changes and the levels of AST, LDH, CK, CK-MB and BNP to normal. Combined treatment with ADI (1, 4, 10%) improved the cell viability, and IC50 increased from 68.51 μM (DOX alone) to 83.47, 176.9, and 310.8 μM, reduced caspase-3 activity by 39.17, 43.96, and 61.82%, respectively. High-dose ADI inhibited the expression of CBR1 protein by 32.3%, reduced DOXol levels in heart, serum and H9c2 cells by 59.8, 72.5 and 48.99%, respectively.

ADI reduces DOX-induced cardiotoxicity by inhibiting CBR1 expression, which provides a scientific basis for the rational use of ADI.

ADI reduces DOX-induced cardiotoxicity by inhibiting CBR1 expression, which provides a scientific basis for the rational use of ADI.Risk management decisions in public health require consideration of a number of complex, often conflicting factors. The aim of this review was to propose a set of 10 fundamental principles to guide risk decision-making. Although each of these principles is sound in its own right, the guidance provided by different principles might lead the decision-maker in different directions. For example, where the precautionary principle advocates for preemptive risk management action under situations of scientific uncertainty and potentially catastrophic consequences, the principle of risk-based decision-making encourages decision-makers to focus on established and modifiable risks, where a return on the investment in risk management is all but guaranteed in the near term. To evaluate the applicability of the 10 principles in practice, one needs to consider 10 diverse risk issues of broad concern and explore which of these principles are most appropriate in different contexts. The 10 principles presented here afford substantive insight into the process of risk management decision-making, although decision-makers will ultimately need to exercise judgment in reaching appropriate risk decisions, accounting for all of the scientific and extra-scientific factors relevant to the risk decision at hand.The formation of new genes is a major source of organism evolutionary innovation. Beyond their mutational effects, transposable elements can be co-opted by host genomes to form different types of sequences including novel genes, through a mechanism named molecular domestication.We report the formation of four genes through molecular domestication of Harbinger transposons, three in a common ancestor of jawed vertebrates about 500 million years ago and one in sarcopterygians approx. 430 million years ago. Additionally, one processed pseudogene arose approx. 60 million years ago in simians. In zebrafish, Harbinger-derived genes are expressed during early development but also in adult tissues, and predominantly co-expressed in male brain. In human, expression was detected in multiple organs, with major expression in the brain particularly during fetal development. We used CRISPR/Cas9 with direct gene knock-out in the F0 generation and the morpholino antisense oligonucleotide knock-down technique to study in zebrafish the function of one of these genes called MSANTD2, which has been suggested to be associated to neuro-developmental diseases such as autism spectrum disorders and schizophrenia in human. MSANTD2 inactivation led to developmental delays including tail and nervous system malformation at one day post fertilization. Affected embryos showed dead cell accumulation, major anatomical defects characterized by impaired brain ventricle formation and alterations in expression of some characteristic genes involved in vertebrate nervous system development. Hence, the characterization of MSANTD2 and other Harbinger-derived genes might contribute to a better understanding of the genetic innovations having driven the early evolution of the vertebrate nervous system.

Hyperparathyroidism (SHPT) secondary to chronic kidney disease (CKD) is characterized by high levels of parathyroid hormone (PTH), hyperplasia of the parathyroid glands and cardiovascular disease. Selective and non-selective and selective vitamin D-receptor activators, calcimimetics, are available in the Brazilian market to reduce PTH levels.

To develop a cost-effectiveness (C/E) and budgetary impact (BI) analysis of intravenous paricalcitol vs. oral calcitriol for patients on dialysis with SHPT, from the perspective of the Brazilian Public Health Care System (SUS).

We built a decision-tree model to analyze C/E, which considered the outcome of avoided death and a time horizon of 1 year. As for the BI analysis, two scenarios were considered, one of demand and one of epidemiological approach, based on data from the Brazilian Society of Nephrology.

The analysis showed that the C/E ratio was R$ 1,213.68 per year, and an incremental effectiveness of 0.032, referring to avoided death. The incremental C/E ratio was R$37,927.50 per death averted by paricalcitol. It was estimated that the incremental BI with the expansion of paricalcitol use will be between R$1,600,202.28 and R$4,128,565.65 in the first year, considering the main and epidemiological scenarios. At the end of 5 years after the expansion of its use, an incremental BI was estimated between R$ 48,596,855.50 and R$ 62,90,555.73.

Intravenous paricalcitol has superior efficacy and similar safety to oral calcitriol, reducing the overall mortality of dialysis patients, although it implies a higher cost.

Intravenous paricalcitol has superior efficacy and similar safety to oral calcitriol, reducing the overall mortality of dialysis patients, although it implies a higher cost.Public and private decision-making on health problems relies on scientific evidence. However, scientific knowledge includes uncertainty, as does knowledge about COVID-19. In an experimental study, we tested how the trustworthiness (on the three dimensions expertise, integrity, and benevolence) of a source of information (either a scientist or a politician), was affected when messages were either two-sided (including arguments pro and contra the effectiveness of mask-wearing) or one-sided (only pro arguments). Results showed that scientists were ascribed more expertise and integrity compared to politicians, and both sources were ascribed more expertise when they gave two-sided (instead of one-sided) information. Moreover, trustworthiness ratings on all three dimensions were affected by participants’ prior topic attitudes and epistemic certainty beliefs. These findings underline that when a source provides two-sided information, this may increase people’s willingness to trust that source. To use this strategy most effectively in health communication, more research should be done on how many and what types of counterarguments to include.Myopericytoma is a rare soft tissue tumor with a predilection for the distal extremities. It is commonly found in the skin and subcutaneous tissues and usually takes a benign course. Current knowledge is limited to isolated case series and reports; hence, this study aims to report our tertiary institution’s experience with this uncommon entity. A review of our institution’s pathology records for cases of myopericytoma was performed. From January 2009 to September 2020, 23 cases of myopericytoma were identified and their clinicopathologic features were reported. A unique case of myopericytoma of the ankle from the series was also highlighted as a case report. Among the 22 cutaneous cases, 18 were in the extremities and 4 in the head and neck. One patient had an intracranial lesion. Most patients developed asymptomatic nodules (72.2%), but 1 patient had a locally aggressive tumor on presentation. None recurred despite marginal excision in some patients (80.0%). In conclusion, pathologists and surgeons who encounter this rare neoplasm can reassure patients of its benign tendency.Data regarding protection against mortality and severe complications after Omicron BA.2 infection with CoronaVac and BNT162b2 vaccines remains limited. We conducted a case-control study to evaluate the risk of severe complications and mortality following 1-3 doses of CoronaVac and BNT162b2 using electronic health records database. Cases were adults with their first COVID-19-related mortality or severe complications between 1 January and 31 March 2022, matched with up-to 10 controls by age, sex, index date, and Charlson Comorbidity Index. Vaccine effectiveness against COVID-19-related mortality and severe complications by type and number of doses was estimated using conditional logistic regression adjusted for comorbidities and medications. Vaccine effectiveness (95% CI) against COVID-19-related mortality after two doses of BNT162b2 and CoronaVac were 90.7% (88.6-92.3) and 74.8% (72.5-76.9) in those aged ≥65, 87.6% (81.4-91.8) and 80.7% (72.8-86.3) in those aged 50-64, 86.6% (71.0-93.8) and 82.7% (56.5-93.1) in those aged 18-50.