Overwhelming Evidence Transplacental Transmission of Human Papillomavirus Primarily Causes Autism

Because the concordance rate between identical twins is only 88%, an environmental factor must cause autism spectrum disorder (ASD). Furthermore, when identical twins share ASD, it is to varying degrees suggesting different prenatal environments exist, which occurs when identical twins have separate placentas (~30% of the time). Placental inclusions are predictive of ASD along with excessive increases in extra-axial cerebral spinal fluid (CSF) detected by MRI in the brains of 6- and 12-month-old infants later diagnosed at 2 years with ASD. The human papillomavirus (HPV) can infect the trophoblast cells of placentas and transmit to the fetus where it infects the epithelial cells of the choroid plexus, a centrally located lining inside the brain responsible for producing CSF via the SLC4A10 gene product. HPV causes epigenetic changes, deletions, and duplications of genes, and besides its characteristic methylation patterns, the SLC4A10 gene was found to be increased in children with ASD. Moreover, male placentas implant close to the cervix (low-lying) three times more often than female placentas paralleling the ASD ratio of ~3:1 (boys to girls). Finally, the Australian HPV vaccination programme that began in 2007 might explain why the 0-4 yr. ASD incidence did not increase from 2010 to 2015.

Long Noncoding RNAs Regulate the Inflammatory Responses of Macrophages

Long noncoding RNAs (lncRNAs) are defined as transcripts with more than 200 nucleotides that have little or no coding potential. In recent years, due to the development of next-generation sequencing (NGS), a large number of studies have revealed that lncRNAs function as key regulators to maintain immune balance and participate in diverse physiological and pathological processes in the human body. Notably, overwhelming evidence suggests that lncRNAs can regulate innate immune responses, the differentiation and development of immune cells, inflammatory autoimmune diseases, and many other immunological processes with distinct regulatory mechanisms. In this review, we summarized the emerging roles of lncRNAs in macrophage development and polarization. In addition, the potential value of lncRNAs as diagnostic biomarkers and novel therapeutic targets for the treatment of aberrant immune responses and inflammatory diseases are discussed.

Central African Republic

Central African Republic (car) has been a theatre of instability for decades, especially following the 2013 coup, which saw crimes that have been found to be premeditated and systematic. This article identifies states collapse, persistent instability and impunity as key factors engendering atrocity crimes in car. Despite the overwhelming evidence of the risk of atrocity crimes, the international response has been inadequate if not passive, and interventions do not consider atrocity prevention in their execution. Thus, subsequent peacebuilding initiatives have not had real and visible impact on the prevention of atrocity crimes. To address this, the establishment of an accountable and functioning state is the overriding condition precedent to preventing and mangaging atrocity crimes in car. The international community should further engage local actors to promote inclusive governance and lay the foundations for stability and sustainable peace. Subsequent restoration of structures for justice and ensuring their effective functioning will help end structural impunity in the country and go a long way in averting future atrocity crimes.

Older Student Experiences: A Critical Examination of Aging on Campus

There is overwhelming evidence that the number of older learners on college campuses has been steadily increasing since the 1970s. The needs of older learners differ from traditional students, and many services and resources available at higher education institutions are geared towards students aged 18-25 (Silverstein, Choi, & Bulot, 2001). Age Friendly University (AFU) principles highlight the need to consider older learners at a university and provide structure to evaluate programs and practices and to enhance inclusion and diversity based upon age. This study examined how an AFU designated university is working to better understand their older students. Methods A web-based pilot survey of older learners (N=248) asked all students ages 40 and older a series of questions regarding motivation to attend school, barriers and supports, campus environment, and connection with AFU principles. Analysis: A regression analysis found that older learners who felt more welcomed by faculty (p=.001), administration (p=.002),and student organizations (p=.026) were more likely to feel connected to campus, and younger-older students (p=.031) and those who did not feel their job was a barrier to attending school (p=.037) were more likely to feel satisfied with their level of engagement on campus. Additionally, older learners felt the AFU principles were demonstrated by their university. Discussion The experiences of older learners are important as we continue to see higher numbers of students over the age of 40. Our results demonstrate the need to engage older learners as part of diversity and inclusion efforts to facilitate connection to the campus community.

On the safety and effectiveness of COVID-19 vaccines, certainties and uncertainties

Introduction: The COVID-19 vaccines in use (inactivaded virus, encapsulated m-RNA, non-replicating adenovirus-vectored DNA) were clinically tested in randomized placebocontrolled phase-3 studies. Objective: To address certainties and uncertainties about safety and effectiveness of COVID-19 vaccines that were approved for use in various countries. Method: The evidence provided by clinical studies on the efficacy and safety of COVID-19 vaccines was critically appraised. Results: COVID-19 vaccines proved to be efficacious and safe in clinical trials. Adverse events were mostly those of minor severity commonly noted with other vaccines such as injection site pain, mild flu-like symptoms, headache and asthenia. Although being very rare, anaphylaxis-like reactions were noted with mRNA vaccines. Uncertainties regarding vaccine effectiveness refer mainly to the (long-term) duration of immunity provided by vaccination, the degree of protection conferred to elderly people, and how effective vaccines are against emerging SARS-CoV-2 variants. There are few uncertainties about vaccine safety including the absence of clinical trial data in pregnant women (and the impact on the unborn child), children and adolescents. Conclusions: Notwithstanding the knowledge gaps about effectiveness and safety of COVID-19 vaccines (to be further addressed by observational studies), there is overwhelming evidence that public health benefits of vaccination by far outweigh any foreseeable risk.

Targeting the Gut Microbiome in Prader-Willi Syndrome

Overwhelming evidence demonstrates an important role of the gut microbiome in the development of a wide range of diseases, including obesity, metabolic disorders, and mental health symptoms. Indeed, interventions targeting the gut microbiome are being actively investigated as a therapeutic strategy to tackle these diseases. Given that obesity and mental health symptoms are both hallmarks of Prader-Willi syndrome, targeting the gut microbiome may be a promising therapeutical strategy. Only a few studies have investigated the gut microbiome in the context of Prader-Willi syndrome and assessed the efficacy of probiotic supplementation as a therapeutic strategy for this disease. Here, we review the knowledge obtained to this date regarding the gut microbiome in individuals with Prader-Willi syndrome. The limited evidence available indicate that probiotic supplementation improves some metabolic and mental health aspects, however further studies are warranted to determine whether targeting the gut microbiome may constitute a safe and efficient strategy to treat individuals with Prader-Willi syndrome.

Return of individual research results from genomic research: A systematic review of stakeholder perspectives

Despite the plethora of empirical studies conducted to date, debate continues about whether and to what extent results should be returned to participants of genomic research. We aimed to systematically review the empirical literature exploring stakeholders’ perspectives on return of individual research results (IRR) from genomic research. We examined preferences for receiving or willingness to return IRR, and experiences with either receiving or returning them. The systematic searches were conducted across five major databases in August 2018 and repeated in April 2020, and included studies reporting findings from primary research regardless of method (quantitative, qualitative, mixed). Articles that related to the clinical setting were excluded. Our search identified 221 articles that met our search criteria. This included 118 quantitative, 69 qualitative and 34 mixed methods studies. These articles included a total number of 118,874 stakeholders with research participants (85,270/72%) and members of the general public (40,967/35%) being the largest groups represented. The articles spanned at least 22 different countries with most (144/65%) being from the USA. Most (76%) discussed clinical research projects, rather than biobanks. More than half (58%) gauged views that were hypothetical. We found overwhelming evidence of high interest in return of IRR from potential and actual genomic research participants. There is also a general willingness to provide such results by researchers and health professionals, although they tend to adopt a more cautious stance. While all results are desired to some degree, those that have the potential to change clinical management are generally prioritized by all stakeholders. Professional stakeholders appear more willing to return results that are reliable and clinically relevant than those that are less reliable and lack clinical relevance. The lack of evidence for significant enduring psychological harm and the clear benefits to some research participants suggest that researchers should be returning actionable IRRs to participants.

Caffeic acid, a dietary polyphenol, as a promising candidate for combination therapy

Increased effectiveness and decreasing toxicity are prime objectives in drug research. Overwhelming evidence suggests the use of appropriate combination therapy for the better efficacy of drugs owing to their synergistic profile. Dietary active constituents play a major role in health outcomes. Therefore, it is possible to increase the effectiveness of the drug by combining contemporary medication with active natural/semi-synthetic constituents. One such dietary constituent, caffeic acid (CA), is a by-product of the shikimate pathway in plants and is a polyphenol of hydroxycinnamic acid class. Extensive research on CA has proposed its efficacy against inflammatory, neurodegenerative, oncologic, and metabolic disorders. The synergistic/additive effects of CA in combination with drugs like caffeine, metformin, pioglitazone, and quercetin have been reported in several experimental models and thus the present review is an attempt to consolidate outcomes of this research. Multi-target-based mechanistic studies will facilitate the development of effective combination regimens of CA.

HEAT SHOCK PROTEIN HSP70: PREREQUISITES FOR USE AS A MEDICINAL PRODUCT

Heat shock protein Hsp70 is one of the main cytoprotection components under the action of various external stimuli. The analysis of the literature data shows that nowadays, the researches’ overwhelming evidence has proven the role of Hsp70 as a biological target for the drug development; however, the ideas about its use as a drug are often multidirectional.The aim of the article is to analyze and generalize the literature data on the features of the physiological functions of heat shock protein Hsp 70, and indicate the possibilities of its use for the pharmacological correction of various pathological conditions.Materials and methods. In the process of selecting material for writing this review article, such databases as Google Patents, Science Research Portal, Google Scholar, ScienceDirect, CiteSeer, Publications, ResearchIndex, Ingenta, PubMed, KEGG, etc. were used The following words and word combinations were selected as markers for identifying the literature: Hsp70, Hsp70 stroke, Hsp70 neuroprotection, Hsp70 cytoprotection, recombinant drugs.Results. In this review, the pharmacology of one of the key members of this family, Hsp70, was focused on. The literary analysis confirms that this molecule is an endogenous regulator of many physiological processes and demonstrates tissue protective effects in modeling ischemic, neurodegenerative and inflammatory processes. The use of recombinant exogenous Hsp70 mimics the endogenous function of the protein, indicating the absence of a number of typical limitations characteristic of pharmacotherapy with high molecular weight compounds, such as immunogenicity, a rapid degradation by proteases, or a low penetration of histohematogenous barriers.Conclusion. Thus, Hsp70 may become a promising agent for clinical trials as a drug for the treatment of patients with neurological, immunological, and cardiovascular profiles.

Commentary: Response to commentary by Bilgin and Wolke (2021)

Recently in this journal, Bilgin and Wolke (2020) published a paper which showed no association between leaving infants to ‘cry it out’ and infant-mother attachment. In our commentary (Davis & Kramer, 2021), we argued that the study was underpowered and, as such, could not be considered a conclusive demonstration that ‘cry it out’ had no adverse effects on attachment. The authors (Bilgin & Wolke, 2021) responded by claiming that, in combination with previous research, there was now ‘overwhelming evidence that letting a baby to cry it out a few times or even often has no adverse effects for infant-mother attachment formation during infancy’ (p. 2). Here, we show that their study was indeed underpowered and argue that there is, as yet, no compelling evidence that ‘cry it out’ is not harmful for attachment. Therefore, this technique should not be utilised by parents until more conclusive evidence has been provided.