Search Results (11)

Background: Newborns, including preterm infants, are capable of responding to pain. Recurrent pain exposure is associated with suboptimal motor development, cognitive impairments, abnormal brain growth, and maladapted nociceptive reactions. Problem: Current agents, primarily opioids and benzodiazepines, raise major concerns due to their adverse effects, including insufficient sedation or analgesia, withdrawal, depressed respiratory effort, tolerance, and occasional paradoxical agitation. Commonly used drugs such as midazolam and morphine have been shown to induce neuroapoptosis and neurodevelopmental abnormalities in animal studies. Evaluation—Dexmedetomidine: As a specific alpha-2 adrenergic agonist, dexmedetomidine causes a significantly lower reduction in breathing effort. It has over 800 times greater affinity for alpha-2 receptors compared to alpha-1 receptors. Common side effects include bradycardia and hypotension. Prolonged use may necessitate a transition to clonidine during the weaning process. Dexmedetomidine can be administered intravenously as a bolus or infusion or intranasally. Indications include sedation and analgesia for mechanical ventilation, therapeutic hypothermia, procedural premedication, and as an adjunct to inhalational anesthesia and nerve-blocking agents. Research across varying age groups has demonstrated that dexmedetomidine shortens periods of invasive ventilation and decreases the need for other sedatives. Neonatal studies suggest that dexmedetomidine may help accelerate the achievement of full enteral feeds and can be safely administered within specific dosage ranges without causing significant adverse events that would necessitate abrupt discontinuation. Conclusions: Dexmedetomidine can be used alone or in combination with other agents. By increasing the use of dexmedetomidine, it is possible to reduce the dosage of concurrent medications, thereby minimizing the risk of complications while still achieving the desired sedation and analgesia. Full article

Background: The aim of this paper is to describe the development of a shared housing model intervention that was designed to serve youth experiencing homelessness who are LGBTQ+ and/or pregnant/parenting. The intervention is built around two guiding philosophies: housing first and restorative justice. Methods: We engaged in a year-long planning process with an advisory group from 1 July 2021 through 30 June 2022. The advisory group is a partnership between Virginia Commonwealth University School of Social Work, seven young people with lived experience expertise, and members from four partner organizations, including local organizations serving LGBTQ+ youth. Results: Marsha and Marian’s Neighbors is designed to provide safe, comfortable housing for 12 months for 20 young people and their children if they have any. Participants will live in apartments where rent and utilities are paid for by the program for all participants. The program also provides money for arrears that may prevent the participants from being able to secure a lease, mental health appointments, legal consultations, and doula services provided by partners recruited by the planning team. Services are provided by staff and partners that are LGBTQ+ affirming and pregnant and parenting affirming. Conclusion: One of the most important lessons that we learned is the power of developing shared values in a novel intervention for LGBTQ+ youth. One focused intervention that supports both pregnant and parenting youth who identify as LGBTQ+ remains necessary. Paradoxically, LGBTQ+ people, particularly bisexual, lesbian, and queer cisgender women, are at an equal or greater risk of unplanned pregnancy. Both groups are vulnerable to housing instability independently, and those who live at the intersection of being LGBTQ+ and pregnant/parenting face an elevated risk for housing instability. Full article

Heparin-induced thrombocytopenia (HIT) is a major issue in cardiac surgery requiring cardiopulmonary bypass (CPB). HIT represents a severe adverse drug reaction after heparin administration. It consists of immune-mediated thrombocytopenia paradoxically leading to thrombotic events. Detection of antibodies against platelets factor 4/heparin (anti-PF4/H) and aggregation of platelets in the presence of heparin in functional in vitro tests confirm the diagnosis. Patients suffering from HIT and requiring cardiac surgery are at high risk of lethal complications and present specific challenges. Four distinct phases are described in the usual HIT timeline, and the anticoagulation strategy chosen for CPB depends on the phase in which the patient is categorized. In this sense, we developed an institutional protocol covering each phase. It consisted of the use of a non-heparin anticoagulant such as bivalirudin, or the association of unfractionated heparin (UFH) with a potent antiplatelet drug such as tirofiban or cangrelor. Temporary reduction of anti-PF4 with intravenous immunoglobulins (IvIg) has recently been described as a complementary strategy. In this article, we briefly described the pathophysiology of HIT and focused on the various strategies that can be applied to safely manage CPB in these patients. Full article

Previous studies have demonstrated an involvement of chromatin-remodelling SWI/SNF complexes in the development of prostate cancer, suggesting both tumor suppressor and oncogenic activities. SMARCD1/BAF60A, SMARCD2/BAF60B, and SMARCD3/BAF60C are mutually exclusive accessory subunits that confer functional specificity and are components of all known SWI/SNF subtypes. To assess the role of SWI/SNF in prostate tumorigenesis, we studied the functions and functional relations of the SMARCD family members. Performing RNA-seq in LnCAP cells grown in the presence or absence of dihydrotestosterone, we found that the SMARCD proteins are involved in the regulation of numerous hormone-dependent AR-driven genes. Moreover, we demonstrated that all SMARCD proteins can regulate AR-downstream targets in androgen-depleted cells, suggesting an involvement in the progression to castration-resistance. However, our approach also revealed a regulatory role for SMARCD proteins through antagonization of AR-signalling. We further demonstrated that the SMARCD proteins are involved in several important cellular processes such as the maintenance of cellular morphology and cytokinesis. Taken together, our findings suggest that the SMARCD proteins play an important, yet paradoxical, role in prostate carcinogenesis. Our approach also unmasked the complex interplay of paralogue SWI/SNF proteins that must be considered for the development of safe and efficient therapies targeting SWI/SNF. Full article

Climate change and continued urban development in flood-prone areas exacerbate flood risks. Flood Risk Management authorities often turn to structural protection measures to minimise losses. However, these measures often lead to infrastructural lock-ins with potential unintended consequences as increased safety can induce increased development, ultimately leading to higher losses in the event of failures of the structural safe-guards in place. This process has been referred to as the Safe Development Paradox: a cross-cutting science-policy-practice challenge that requires a systematic understanding in the context of climate change and the United Nations Sustainable Development Goals. Yet, there are no comprehensive review studies, to date, that summarize the state of knowledge of the Safe Development Paradox. This paper provides the first evidence base through a critical review of the state-of-the-art and quantitative analysis of the peer-reviewed English-language literature since 2000, highlighting key knowledge gaps and issues hindering progress in addressing the Safe Development Paradox. It was identified that current research is compounded by a lack of consistent terminology, limited geographic distribution of case studies, and skewed emphasis on fluvial flooding. The review ends with potential directions across the science, policy, and practice domains for increasing knowledge and tackling the Safe Development Paradox. Full article

Cancer is a disease of high mortality, and its prevalence has increased steadily in the last few years. However, during the last decade, the development of modern chemotherapy schemes, new radiotherapy techniques, targeted therapies and immunotherapy has brought new hope in the treatment of these diseases. Unfortunately, cancer therapies are also associated with frequent and, sometimes, severe adverse events. Ascorbate (ascorbic acid or vitamin C) is a potent water-soluble antioxidant that is produced in most mammals but is not synthesised endogenously in humans, which lack enzymes for its synthesis. Ascorbate has antioxidant effects that correspond closely to the dose administered. Interestingly, this natural antioxidant induces oxidative stress when given intravenously at a high dose, a paradoxical effect due to its interactions with iron. Importantly, this deleterious property of ascorbate can result in increased cell death. Although, historically, ascorbate has been reported to exhibit anti-tumour properties, this effect has been questioned due to the lack of available mechanistic detail. Recently, new evidence has emerged implicating ferroptosis in several types of oxidative stress-mediated cell death, such as those associated with ischemia–reperfusion. This effect could be positively modulated by the interaction of iron and high ascorbate dosing, particularly in cell systems having a high mitotic index. In addition, it has been reported that ascorbate may behave as an adjuvant of favourable anti-tumour effects in cancer therapies such as radiotherapy, radio-chemotherapy, chemotherapy, immunotherapy, or even in monotherapy, as it facilitates tumour cell death through the generation of reactive oxygen species and ferroptosis. In this review, we provide evidence supporting the view that ascorbate should be revisited to develop novel, safe strategies in the treatment of cancer to achieve their application in human medicine. Full article

The multistep translational science behind new drugs comprehends the entire process through laboratory, clinical, and community observations turned into health interventions. The development of new drug options from discovering targets and leading compounds in basic research for implementing therapeutic guidelines contributes to the emergence of health policies essential for infection control. This review updates the translational research in the scenario of the most common non-viral sexually transmitted infection (STI), trichomoniasis. Paradoxically to its high occurrence, it is considered neglected since notification is not mandatory. It turns into a stable disease with health complications, and receives little emphasis from public health programs to control STI. Although related to curable STIs, the current drugs, metronidazole and tinidazole, present therapeutic failures. The need for new options to treat trichomoniasis is established by basic research studies and patents revealing novel synthetic compounds and natural products presenting anti-Trichomonas vaginalis activities, mainly based on in vitro findings. Clinical trials are still focused on new routes of administration for conventional drugs. In addition, nanotechnology approaches are in their infancy, shedding light on potential possibilities for creating more effective, targeted, and safe delivery systems. Overall, the novel proposed approaches need, in addition to pharmaceutical development and efficacy assessments, to ensure that the quality requirements for their use as medicines are met. It is essential to overcome these issues to cross the “Death Valley” of drug discovery and to advance in the translational science criteria in the trichomoniasis drug development field. Full article

The hepatitis A virus (HAV) is a leading cause of acute viral hepatitis worldwide. It is transmitted mainly by direct contact with patients who have been infected or by ingesting contaminated water or food. The virus is endemic in low-income countries where sanitary and sociodemographic conditions are poor. Paradoxically, improving sanitary conditions in these countries, which reduces the incidence of HAV infections, can lead to more severe disease in susceptible adults. The populations of developed countries are highly susceptible to HAV, and large outbreaks can occur when the virus is spread by globalization and by increased travel and movement of foodstuffs. Most of these outbreaks occur among high-risk groups: travellers, men who have sex with men, people who use substances, and people facing homelessness. Hepatitis A infections can be prevented by vaccination; safe and effective vaccines have been available for decades. Several countries have successfully introduced universal mass vaccination for children, but high-risk groups in high-income countries remain insufficiently protected. The development of HAV antivirals may be important to control HAV outbreaks in developed countries where a universal vaccination programme is not recommended. Full article

Coronavirus 2019 (COVID-19) has created a global pandemic that is devastating human lives, public healthcare systems, and global economies. Multiple effective and safe COVID-19 vaccines have been developed at an unprecedented speed due to the efforts of the scientific community, and collaboration between the federal government and pharmaceutical companies. However, the continued exclusion of pregnant and lactating women from the COVID anti-viral and vaccine trials has created the paradox of a lack of empirical evidence in a high-risk population. Based on the experience of similar prior vaccines, animal developmental and reproductive toxicology studies, and preliminary findings from human studies, various healthcare professional advisory committees (Advisory Committee on Immunization Practices, American College of Obstetricians and Gynecologists, Society for Maternal-Fetal Medicine, and Academy of Breastfeeding Medicine) have issued guidance supporting COVID-19 vaccination in pregnant and lactating women. In this article, we summarize the available data on the efficacy and safety profile of COVID-19 vaccination in pregnant and lactating women, review the challenges of vaccine hesitancy, and include recommendations for healthcare providers. Full article

The Sustainable Development Goals (SDGs) of the United Nations state that cities and human settlements need to be more inclusive, safe and resilient. In Europe cities have experienced dramatic physical, social and economic changes during the last decades while historic centres of European cities, among the most important assets of the European cultural heritage, are living paradoxes. They are defined as “a collection of beauty, icon of well-being, model of sustainability, but abandoned”. This study investigates the changes in the urban landscape of Nicosia, a particular historical centre in the Mediterranean region (Cyprus). The city centre is characterised by exceptionally well-preserved Venetian fortifications. Due to political circumstances, the capital of Cyprus, Nicosia, is still divided and has been ruled by two different administrations for several decades. This study used optical multi-spectral satellite datasets processing, like the Landsat and the most recent Sentinel-2 products, to detect, identify and characterise significant morphological transformations within the walled city and around it. This paper’s central thesis promotes a more systematic use of earth observation products and derivatives in decision-making processes that regard planning, use and management of urban resources in Europe, especially in support of urban planning strategies of historic cities. Full article

The Indonesian construction industry is the second largest in Asia and accounts for over 30% of all occupational injuries in the country. Despite the size of the industry, there is a lack of safety research in this context. This research, therefore, aims to assess safety climate and develop a framework to improve safety in the Indonesian construction industry. Quantitative and qualitative data were collected from 311 construction workers. The results show a moderately healthy safety climate but reflect numerous problems, particularly around perceived conflicts between production and safety logics, cost trade-offs being made against other competing project priorities, poor safety communication, poor working conditions, acceptance of poor safety as the norm, poor reporting and monitoring practices, poor training and a risky and unsupportive working environment which prevents workers from operating safely. Two new safety climate paradoxes are also revealed: contradictions between management communications and management practices; contradictions between worker concern for safety and their low sense of personal accountability and empowerment for acting to reduce these risks. A low locus of control over safety is also identified as a significant problem which is related to prevailing Indonesian cultural norms and poor safety policy implementation and potential conflicts between formal and informal safety norms, practices and procedures. Drawing on these findings, a new integrated framework of safety climate is presented to improve safety performance in the Indonesian construction industry. Full article