SUMMARYIn recent decades, several new diseases have emerged in different geographical areas, with pathogens including Ebola virus, Zika virus, Nipah virus, and coronaviruses (CoVs). Recently, a new ...type of viral infection emerged in Wuhan City, China, and initial genomic sequencing data of this virus do not match with previously sequenced CoVs, suggesting a novel CoV strain (2019-nCoV), which has now been termed severe acute respiratory syndrome CoV-2 (SARS-CoV-2). Although coronavirus disease 2019 (COVID-19) is suspected to originate from an animal host (zoonotic origin) followed by human-to-human transmission, the possibility of other routes should not be ruled out. Compared to diseases caused by previously known human CoVs, COVID-19 shows less severe pathogenesis but higher transmission competence, as is evident from the continuously increasing number of confirmed cases globally. Compared to other emerging viruses, such as Ebola virus, avian H7N9, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV-2 has shown relatively low pathogenicity and moderate transmissibility. Codon usage studies suggest that this novel virus has been transferred from an animal source, such as bats. Early diagnosis by real-time PCR and next-generation sequencing has facilitated the identification of the pathogen at an early stage. Since no antiviral drug or vaccine exists to treat or prevent SARS-CoV-2, potential therapeutic strategies that are currently being evaluated predominantly stem from previous experience with treating SARS-CoV, MERS-CoV, and other emerging viral diseases. In this review, we address epidemiological, diagnostic, clinical, and therapeutic aspects, including perspectives of vaccines and preventive measures that have already been globally recommended to counter this pandemic virus.
Alzheimer’s disease (AD) is increasingly prevalent worldwide, and disease‐modifying treatments may soon be at hand; hence, now, more than ever, there is a need to develop techniques that allow ...earlier and more secure diagnosis. Current biomarker‐based guidelines for AD diagnosis, which have replaced the historical symptom‐based guidelines, rely heavily on neuroimaging and cerebrospinal fluid (CSF) sampling. While these have greatly improved the diagnostic accuracy of AD pathophysiology, they are less practical for application in primary care, population‐based and epidemiological settings, or where resources are limited. In contrast, blood is a more accessible and cost‐effective source of biomarkers in AD. In this review paper, using the recently proposed amyloid, tau and neurodegeneration AT(N) criteria as a framework towards a biological definition of AD, we discuss recent advances in biofluid‐based biomarkers, with a particular emphasis on those with potential to be translated into blood‐based biomarkers. We provide an overview of the research conducted both in CSF and in blood to draw conclusions on biomarkers that show promise. Given the evidence collated in this review, plasma neurofilament light chain (N) and phosphorylated tau (p‐tau; T) show particular potential for translation into clinical practice. However, p‐tau requires more comparisons to be conducted between its various epitopes before conclusions can be made as to which one most robustly differentiates AD from non‐AD dementias. Plasma amyloid beta (A) would prove invaluable as an early screening modality, but it requires very precise tests and robust pre‐analytical protocols.
Abstract X-linked juvenile retinoschisis (XLRS) is a retinal degenerative disorder caused by mutations in the RS1 gene encoding a protein termed retinoschisin. The disease is an excellent candidate ...for gene replacement therapy as the majority of mutations have been shown to lead to a complete deficiency of the secreted protein in the retinal structures. In this work, we have studied the ability of non-viral vectors based on solid lipid nanoparticles (SLN) to induce the expression of retinoschisin in photoreceptors (PR) after intravitreal administration to Rs1h-deficient mice. We designed two vectors prepared with SLN, protamine, and dextran (DX) or hyaluronic acid (HA), bearing a plasmid containing the human RS1 gene under the control of the murin opsin promoter (mOPS). In vitro, the nanocarriers were able to induce the expression of retinoschisin in a PR cell line. After injection into the murine vitreous, the formulation prepared with HA induced a higher transfection level in PR than the formulation prepared with DX. Moreover, the level of retinoschisin in the inner nuclear layer (INL), where bipolar cells are located, was also higher. Two weeks after vitreal administration into Rs1h-deficient mice, both formulations showed significant improvement of the retinal structure by inducing a decrease of cavities and PR loss, and an increase of retinal and outer nuclear layer (ONL) thickness. HA-SLN resulted in a significant higher increase in the thickness of both retina and ONL, which can be explained by the higher transfection level of PR. In conclusion, we have shown the structural improvement of the retina of Rs1h-deficient mice with PR specific expression of the RS1 gene driven by the specific promoter mOPS, after successful delivery via SLN-based non-viral vectors.
Wave interference is a fundamental manifestation of the superposition principle with numerous applications. Although in conventional optics, interference occurs between waves undergoing different ...phase advances during propagation, we show that the vectorial structure of the near field of an emitter is essential for controlling its radiation as it interferes with itself on interaction with a mediating object. We demonstrate that the near-field interference of a circularly polarized dipole results in the unidirectional excitation of guided electromagnetic modes in the near field, with no preferred far-field radiation direction. By mimicking the dipole with a single illuminated slit in a gold film, we measured unidirectional surface-plasmon excitation in a spatially symmetric structure. The surface wave direction is switchable with the polarization.
Objective
To assess the association and magnitude of the effect of early exposure to different types of interpersonal violence (IPV) with suicide attempt and suicide death in youths and young adults.
...Method
We searched six databases until June 2015. Inclusion criteria were as follows: (1) assessment of any type of IPV as risk factor of suicide attempt or suicide: (i) child maltreatment childhood physical, sexual, emotional abuse, neglect, (ii) bullying, (iii) dating violence, and (iv) community violence; (2) population‐based case–control or cohort studies; and (3) subjects aged 12–26 years. Random models were used for meta‐analyses (Reg: CRD42013005775).
Results
From 23 682 articles, 29 articles with 143 730 subjects for meta‐analyses were included. For victims of any IPV, OR of subsequent suicide attempt was 1.99 (95% CI: 1.73–2.28); for child maltreatment, 2.25 (95% CI: 1.85–2.73); for bullying, 2.39 (95% CI: 1.89–3.01); for dating violence, 1.65 (95% CI: 1.40–1.94); and for community violence, 1.48 (95% CI: 1.16–1.87). Young victims of IPV had an OR of suicide death of 10.57 (95% CI: 4.46–25.07).
Conclusion
Early exposure to IPV confers a risk of suicide attempts and particularly suicide death in youths and young adults. Future research should address the effectiveness of preventing and detecting early any type of IPV exposure in early ages.
The current literature shows increasing concerns about potential seminal transmission of monkeypox virus (MPXV). Accordingly, we aimed to understand better the potential presence of MPXV in the ...seminal fluids and others specimens obtained from MPX cases. On June 26, 2022, a systematic search of the literature was conducted to find articles that examine the presence of MPXV in the seminal fluid of confirmed cases. The search was updated once on August 12 and another on October 12, 2022, to include newly published articles. The prevalence of MPXV DNA presence in the seminal fluid and other specimens was pooled in a meta‐analysis (from studies with sample size > 5 to reduce overestimation) and results were presented as effect sizes (ES) and their corresponding 95% confidence intervals (CI). Nine articles were included. Only five studies were eligible for a meta‐analysis, and the pooled prevalence of MPXV DNA in semen specimens was 72.4% (95% CI: 55.7%−84.5%) among 115 patients. The positive rate of MPXV viral polymerase chain reaction (PCR) was higher among skin samples (89%; 95% CI: 78.2%−94.8%; N = 62; studies = 2), followed by anogenital/rectal samples (74.3%; 95% CI: 60.4%−84.5%; N = 54; studies = 2). On the other hand, the positivity rate was lower in nasopharyngeal (62.4%; 95% CI: 20.4%−91.5%; N = 587; studies = 3), urine (21.1%; 95% CI: 4.3%−61.1%; N = 617; studies = 4), and blood/plasma (14.3%; 95% CI: 11.3%−18.1%; N = 609; studies = 3) samples. Besides, MPXV can be detected in semen early from Day 1 and up to 19 days after symptoms onset. Finally, two articles investigated the infectivity of MPXV particles detected in seminal specimens by testing their replication competence. Culturing MPXV was successful in two out of four patients included in these studies. MPXV is highly prevalent in seminal specimens of MPX cases, further corroborating the role of sexual transmission of the disease. However, further evidence is still needed to shed more light on the replication competence of these particles.
The incidence of inflammatory bowel disease (IBD) is rising with 25% of IBD diagnosed in children under 18 years of age. The clinical presentation of IBD in children is often vague leading to initial ...misdiagnosis as infectious colitis or irritable bowel syndrome. When IBD is identified, overlap in histologic and endoscopic features may lead to difficulty distinguishing Crohn’s disease from ulcerative colitis, resulting in a higher frequency of the diagnosis indeterminate colitis or IBD unspecified. Recognizing the common and the atypical presentation of pediatric IBD and extraintestinal manifestations will aid in expeditious referral and early diagnosis. Activity severity scoring tools and more specific classification systems for pediatric IBD direct therapeutic algorithms and allow for improved longitudinal assessment since disease severity and location have been shown to be associated with outcome.
Overactive Janus kinases (JAKs) are known to drive leukemia, making them well-suited targets for treatment. We sought to identify new JAK-activating mutations and instead found a JAK1-inactivating ...pseudokinase mutation, V666G. In contrast to other pseudokinase mutations that canonically lead to an active kinase, the JAK1 V666G mutation led to under-activation seen by reduced phosphorylation. To understand the functional role of JAK1 V666G in modifying kinase activity we investigated its influence on other JAK kinases and within the Interleukin-2 pathway. JAK1 V666G not only inhibited its own activity, but its presence could inhibit other JAK kinases. These findings provide new insights into the potential of JAK1 pseudokinase to modulate its own activity, as well as of other JAK kinases. Thus, the features of the JAK1 V666 region in modifying JAK kinases can be exploited to allosterically inhibit overactive JAKs.
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