Pristol Pharmaceuticals

In a recent review published in Infectious Medicine, researchers summarized the epidemiology, etiology, clinical presentation, diagnosis and prevention and treatment strategies for monkeypox (MPX) caused by the monkeypox virus (MPXV).

An unexpected MPX outbreak in several non-endemic nations has raised global concerns. Most MPX cases of the ongoing 2022 outbreak were identified in gay, bisexual, or other men who have sex with men (GBMSM) with atypical clinical presentations. Prevention and control measures must be rapidly developed and adopted to prevent efficient human-to-human transmission of MPXV across the globe.

About the review

In the present review, researchers summarized the epidemiology, etiology, clinical presentation, diagnosis, and prevention and treatment strategies for MPX.

Epidemiology of MPX

MPXV was initially discovered in a Danish laboratory in 1958. The first human case of MPX was reported in 1970 in a nine-month-old male infant during smallpox eradication in the Democratic Republic of the Congo (DRC) and by 1980, MPX cases were nine times higher than the previous year in DRC. Between 1996 and 1997, an MPX outbreak occurred in the DRC with 511 MPX cases.

By 2009, 92 cases were reported in Africa and the count increased to 277 cases by 2019 in Africa. In September 2017, the largest MPX outbreak occurred in Nigeria, caused by a West African clade strain. From 2017 to 2019, 183 MPX cases were reported, increasing to 502 cases by October 2021. On 7 May 2022, the UK Health Security Agency (UKHSA) reported MPXV in an individual who had traveled to Nigeria. A week later, two MPX cases were reported with no travel history to Nigeria.  

After that, MPXV was detected in many non-endemic nations, and most non-endemic MPX cases reported a history of visits to North America and Europe. Between 1 January and 22 June 2022, 3413 MPX cases were reported across 50 nations/territories, 86% of which belonged to Europe, and MPXV was detected in China on 24 June 2022 and also in the United Kingdom (UK).

MPX etiology

MPXV is a linear, enveloped, double-stranded deoxyribonucleic acid (dsDNA) virus belonging to the Orthopoxvirus genus within the Poxviridae family with intracytoplasmic replication. The virus mainly comprises four components, namely, the outer envelope comprising lipoproteins, the lateral bodies, the outer membrane, and the inner core. The ends of the MPXV genome comprise the inverted terminal repeat (ITR) sequence and 190 open reading frames (ORFs) with more than >180 nucleotides.

MPXV sequences have been phylogenetically grouped into the West Africa clade and the Congo Basin or Central Africa clade with case fatality rates of 3.6% and 10.6%, respectively. MPXV detected in 2022 has been found to contain 50 single nucleotide polymorphisms (SNPs), exceeding the previous mutation rates for Orthopoxviruses, indicative of increased MPXV adaptability to human beings.

Transmission and clinical manifestations of MPX

MPX is primarily a zoonotically transmitted infection and MPXV has several animal reservoirs such as chimpanzees, monkeys of Kenya, elephants of Africa, wild boar, antelope, Gambian rats, dogs, anteaters and squirrels of West Africa. MPXV is transmitted on exposure of a human to an MPXV-infected animal/person/ or MPXV-contaminated material via animal to person or from person to person via contact with infectious ulcers, body fluids, scabs, or materials contaminated by MPXV or through respiratory droplets, sex or intimate contact. Individuals not receiving smallpox vaccinations are at an increased risk of MPX infections.

MPX symptoms are similar but less severe than smallpox symptoms and MPXV incubates for one to two weeks; however, the severity of MPX symptoms may increase in children, immunocompromised individuals and pregnant females. In the initial invasion phase (five days), patients experience chills, fever, intense headaches, lymphadenopathy, asthenia, exhaustion, myalgia and back pain.

Within one to three days of fever onset, the skin eruption phase commences characterized by a rash beginning on the patient’s face followed by rapidly spreading to the extremities, hand palms and feet soles, oral cavity, conjunctiva and the cornea in a centrifugal manner. Skin lesions begin as macules, papules, vesicles, and pustules that develop crusting and turn into scabs that eventually fall off in two to four weeks. Notably, MPX cases in the ongoing 2022 outbreak have presented atypical clinical presentations with initially a genital or perianal rash in MSM individuals.

Diagnosis, treatment and prevention of MPX

Specimens for MPXV testing include those obtained from the surface, exudate, roof or crust swabs from skin lesions, saliva and nasopharyngeal swabs.  MPX is primarily diagnosed based on viral isolation and real-time reverse transcription-polymerase chain reaction (RT-PCR). As secondary tests, acute and convalescent serum samples may be used to detect anti-MPXV immunoglobulin M (IgM) and IgG.

To date, no MPXV-specific treatment is available and antivirals such as brincidofovir, cidofovir and tecovirimat may provide supportive and symptomatic treatment by alleviation of symptoms by reducing disease sequelae, and by managing complications. MPX patients must remain isolated until the scabs fall off and use designated items such as towels, clothes, and utensils.

Conclusions

The authors stated three main reasons for the ongoing 2022 outbreak, which are as follows: (i) MPX has caused mild symptoms, and thus, MPXV transmission has not been controlled well in time; (ii) MPXV sequences mutated faster than expected during the current MPX outbreak and; (iii) Herd immunity declined with time ever since the discontinuity of vaccinations against smallpox in the 1970s.

MPX is an international health concern that warrants coordinated global efforts to enhance awareness, increase MPXV testing, develop effective antivirals, disinfect spaces and adopt preventive strategies to limit MPXV transmission. Strict quarantine measures must be undertaken, the import of African primates and rodents must be restricted and the JYNNEOS or ACAM2000 vaccinations must be administered, especially to individuals in close contact with MPX patients. In addition, smallpox vaccinations may be made available in cases of emergency.

Journal reference:

• Qin Luo, Jun Han. (2022). Preparedness for a Monkeypox Outbreak. Infectious Medicine. doi: https://doi.org/10.1016/j.imj.2022.07.001 https://www.sciencedirect.com/science/article/pii/S2772431X22000259

Many of today’s high-demand jobs were created in the last decade, according to the International Society for Technology in Education (ISTE). As advances in technology drive globalization and digital transformation, teachers can help students acquire the necessary skills to succeed in the careers of the future.

How important is technology in education? The COVID-19 pandemic is quickly demonstrating why online education should be a vital part of teaching and learning. By integrating technology into existing curricula, as opposed to using it solely as a crisis-management tool, teachers can harness online learning as a powerful educational tool.

The effective use of digital learning tools in classrooms can increase student engagement, help teachers improve their lesson plans, and facilitate personalized learning. It also helps students build essential 21st-century skills.

Virtual classrooms, video, augmented reality (AR), robots, and other technology tools can not only make class more lively, they can also create more inclusive learning environments that foster collaboration and inquisitiveness and enable teachers to collect data on student performance.

Still, it’s important to note that technology is a tool used in education and not an end in itself. The promise of educational technology lies in what educators do with it and how it is used to best support their students’ needs.

Educational Technology Challenges

BuiltIn reports that 92 percent of teachers understand the impact of technology in education. According to Project Tomorrow, 59 percent of middle school students say digital educational tools have helped them with their grades and test scores. These tools have become so popular that the educational technology market is projected to expand to $342 billion by 2025, according to the World Economic Forum.

However, educational technology has its challenges, particularly when it comes to implementation and use. For example, despite growing interest in the use of AR, artificial intelligence, and other emerging technology, less than 10 percent of schools report having these tools in their classrooms, according to Project Tomorrow. Additional concerns include excessive screen time, the effectiveness of teachers using the technology, and worries about technology equity.

Prominently rising from the COVID-19 crisis is the issue of content. Educators need to be able to develop and weigh in on online educational content, especially to encourage students to consider a topic from different perspectives. The urgent actions taken during this crisis did not provide sufficient time for this. Access is an added concern — for example, not every school district has resources to provide students with a laptop, and internet connectivity can be unreliable in homes.

Additionally, while some students thrive in online education settings, others lag for various factors, including support resources. For example, a student who already struggled in face-to-face environments may struggle even more in the current situation. These students may have relied on resources that they no longer have in their homes.

Still, most students typically demonstrate confidence in using online education when they have the resources, as studies have suggested. However, online education may pose challenges for teachers, especially in places where it has not been the norm.

Despite the challenges and concerns, it’s important to note the benefits of technology in education, including increased collaboration and communication, improved quality of education, and engaging lessons that help spark imagination and a search for knowledge in students.

The Benefits of Technology in Education

Teachers want to improve student performance, and technology can help them accomplish this aim. To mitigate the challenges, administrators should help teachers gain the competencies needed to enhance learning for students through technology. Additionally, technology in the classroom should make teachers’ jobs easier without adding extra time to their day.

Technology provides students with easy-to-access information, accelerated learning, and fun opportunities to practice what they learn. It enables students to explore new subjects and deepen their understanding of difficult concepts, particularly in STEM. Through the use of technology inside and outside the classroom, students can gain 21st-century technical skills necessary for future occupations.

Still, children learn more effectively with direction. The World Economic Forum reports that while technology can help young students learn and acquire knowledge through play, for example, evidence suggests that learning is more effective through guidance from an adult, such as a teacher.

Leaders and administrators should take stock of where their faculty are in terms of their understanding of online spaces. From lessons learned during this disruptive time, they can implement solutions now for the future. For example, administrators could give teachers a week or two to think carefully about how to teach courses not previously online. In addition to an exploration of solutions, flexibility during these trying times is of paramount importance.

Below are examples of how important technology is in education and the benefits it offers to students and teachers.

Increased Collaboration and Communication

Educational technology can foster collaboration. Not only can teachers engage with students during lessons, but students can also communicate with each other. Through online lessons and learning games, students get to work together to solve problems. In collaborative activities, students can share their thoughts and ideas and support each other. At the same time, technology enables one-on-one interaction with teachers. Students can ask classroom-related questions and seek additional help on difficult-to-understand subject matter. At home, students can upload their homework, and teachers can access and view completed assignments using their laptops.

Personalized Learning Opportunities

Technology allows 24/7 access to educational resources. Classes can take place entirely online via the use of a laptop or mobile device. Hybrid versions of learning combine the use of technology from anywhere with regular in-person classroom sessions. In both scenarios, the use of technology to tailor learning plans for each student is possible. Teachers can create lessons based on student interests and strengths. An added benefit is that students can learn at their own pace. When they need to review class material to get a better understanding of essential concepts, students can review videos in the lesson plan. The data generated through these online activities enable teachers to see which students struggled with certain subjects and offer additional assistance and support.

Curiosity Driven by Engaging Content

Through engaging and educational content, teachers can spark inquisitiveness in children and boost their curiosity, which research says has ties to academic success. Curiosity helps students get a better understanding of math and reading concepts. Creating engaging content can involve the use of AR, videos, or podcasts. For example, when submitting assignments, students can include videos or interact with students from across the globe.

Improved Teacher Productivity and Efficiency

Teachers can leverage technology to achieve new levels of productivity, implement useful digital tools to expand learning opportunities for students, and increase student support and engagement. It also enables teachers to improve their instruction methods and personalize learning. Schools can benefit from technology by reducing the costs of physical instructional materials, enhancing educational program efficiency, and making the best use of teacher time.

Become a Leader in Enriching Classrooms through Technology

Educators unfamiliar with some of the technology used in education may not have been exposed to the tools as they prepared for their careers or as part of their professional development. Teachers looking to make the transition and acquire the skills to incorporate technology in education can take advantage of learning opportunities to advance their competencies. For individuals looking to help transform the education system through technology, American University’s School of Education Online offers a Master of Arts in Teaching and a Master of Arts in Education Policy and Leadership to prepare educators with essential tools to become leaders. Courses such as Education Program and Policy Implementation and Teaching Science in Elementary School equip graduate students with critical competencies to incorporate technology into educational settings effectively.

Learn more about American University’s School of Education Online and its master’s degree programs.

In scientific research, SNP is a term that is frequently used, but what is SNP exactly, why do we study SNP, and how do we carry out research work?

What is SNP?

SNP, or Single nucleotide polymorphism, refers to the diversity of DNA sequences attributable to insertions or deletions, single nucleotide transitions, and transversions with a variation frequency of >1%.

SNPs are abundant, and there are around 3 × 10⁶ SNP sites in the human body, with an average of 1 in 500-1000 base pairs. Among the vast number of SNP loci in the human body, it is limited to those that can cause amino acid changes, contingent on the position of the SNP and the type of mutation.

As illustrated in the figure below, only SNPs with non-synonymous mutations in the coding gene region produce phenotypic changes.

Image Credit: Nanjing Vazyme Biotech Co., Ltd

SNPs are affiliated with drug susceptibility, disease susceptibility and individual phenotypic differences. They possess significant research value in precise nutrition, disease diagnosis and screening, and medication guidance. They are closely connected to our daily lives.

Studies have shown that SNP loci and related genes which may be associated with the symptoms of COVID-19 have been discovered.¹ During its evolution, numerous SNP loci appeared in the COVID-19 virus, some of which could create a new variant of the coronavirus disease that has a potential risk of increasing virulence and infectiousness.

Research on SNPs can be split into two categories:

1. Evaluation of unknown SNPs, such as identifying new SNP sites and establishing the relationship between an unknown SNP and genetic disease.
2. Analysis of known SNPs, such as genetic diversity studies of SNPs across various groups and genetic diagnosis of genetic diseases. 

The most commonly used methods for detecting SNPs

SNP detection is primarily carried out by PCR and sequencing. The base and site of mutation can be established using detection. These methods, according to the detection throughput, can be split into two main categories: low-throughput and high-throughput. 

The low-throughput method has the potential to detect dozens of SNPs in one experiment, while the high-throughput method can detect SNPs in their thousands at one time. 

Low-throughput methods include Sanger sequencing, Taqman probes, and mass spectrometry detection. 

Sanger sequencing

Sanger sequencing relies on dideoxynucleotide termination reaction to produce fragments that vary in length for sequencing. Considered the “gold standard” for SNP detection, Sanger sequencing not only has the capacity to determine the type and location of mutations but also identify unknown SNP sites.

The throughput of Sanger sequencing is low, and the cost is comparatively high. Sanger sequencing is appropriate for analyzing fewer sites and fewer samples. 

Antibiotic treatment alters the composition and magnitude of got microbiota species. Overall, antibiotics reduce species’ diversity and include the loss of key functional taxa, resulting in shifts in metabolism, increasing the susceptibility of the gut to colonization, and the stimulation of bacterial antibiotic resistance.

The therapeutic or prophylaxis-use antimicrobial drugs on the gastrointestinal microbiota cause disturbances in the microbial equilibrium. The extent of these alterations, alongside this lack of equilibrium in the ecology of the microbiota, is dependent on the nature and pharmacokinetic profile of the drug.

What is the Gut Microbiome?

The microbiota is the collection of microorganisms present in a particular environment. The term microbiome refers to the environment, including the totality of all microorganisms (bacteria, eukaryotes, archaea, and viruses) and their genomes and the environmental conditions present in the environment. The collection of bacteria, Archaea, eukaryotes, and viruses present in the gastrointestinal tract of humans is collectively called the human gut microbiota.

The Functional Effect of Antibiotics on the Gut

There is an inverse relationship between the use of antibiotics and microbial diversity. Moreover, the mode by which antibiotics are delivered exerts different effects.

Following antibacterial treatment, diversity restoration takes ~1 month; in adults, restoration requires ~1.5 months. In adults, administering a combination of several different types of antibiotics (meropenem, gentamicin, and vancomycin) can increase the prevalence of certain species of Enterobacteriaceae alongside other pathobionts with a concomitant decrease in butyrate-producing species. 

Antibiotics Alter the Balance of Microbial Species

Antibiotics are destabilizing agents that challenge the balance of gut microbial species. This disruption in balance is manifested as decreased species diversity with concomitant overgrowth of pathogenic species, known as pathobionts, such as C difficile.

Treatments with antibiotics are successful in eliminating the antibiotic susceptible species. However, antibiotic-resistant bacteria typically multiply and take their place. The total microbial load has been observed to increase following antibiotic treatment, despite decreasing species diversity. In a study of patients treated with broad-spectrum antibiotics, the microbial load in fecal samples was increased twofold over seven days following treatment with B-lactams, with an increased ratio of Bacteroidetes to Firmicute.

Moreover, the metabolization of drugs occurs in the intestine due to the possession of vast quantities of cytochrome P450 (CYP) enzymes. These CYP enzymes are responsible pick catalyzing phase one and phase two drug metabolism reactions. In response to oral antibiotic therapy using macrolides, shifts in the intestinal microbiota occur, specifically regarding the relative abundance of bacteroids and bifidobacterium. As stated previously, this produces a niche that accommodates the growth of C difficile.

In a similar vein, the overuse of antibiotics can negatively affect both the proliferation or apoptosis of intestinal cells, which range from enterocytes to endocrine cells. This results in the release of intracellular proteins, useful markers of gut microbiome dysregulation. In a study of the gut microbiota of 1135 participants, researchers found a connection between the microbiome and different host factors; specifically, fecal chromogranin A was associated with the presence of a particular species of microbe.

In a study conducted in Finland, children between two and seven years old were subject to treatment with macrolides, a class of antibiotics that includes erythromycin, roxithromycin, azithromycin, and clarithromycin. This treatment was associated with a shift in the composition of intestinal flora that persisted long term. This shift resulted in a shift in human gut metabolism; this was noted when children under macrolide treatment were compared to a non-antibiotic treatment group.

Among children who were not exposed to antibiotics, the abundance of Collinsella, Lactobacillus, and Anaerostipes was observed; these populations were lower in those treated with antibiotics. Other changes observed in microbial populations include a reduction in the diversity and maturity of the microbiota over two years. Moreover, some populations returned faster than others, with Bacteroides and Bifidobacterium recovering to pre-antibiotic status within a year after macrolide administration.

Interestingly, children receiving antibiotics more frequently experienced bacterial infections relative to those who did not; this is due to the interdependence on the interrelation of microbes in the gut; the removal of large quantities of bacteria results in the overall diminishment in the function of commensal bacteria.

The Impact of Antibiotics on Gut Microbiota Pre and Post Birth

The transmission of antibiotic-resistant strains from mother to infant is currently understudied. However, it is known that the programming of the immune system is strongly influenced by the bacteria that first colonize the gut. This form of colonization is called vertical transmission. The vertical antibiotic-resistant strain transfer mechanism occurs during both placental and vaginal birth, through breast milk, and transfer of antibiotics in utero.

Antibiotic exposure in a neonate cohort of 12,422 showed a gain in height and weight among boys with a higher body mass index. In both genders, there was a decrease in fecal bifidobacterium diversity. A follow-up study using mice model experiments in which fecal microbial transfer from children exposed to antibiotics impacted growth. This was associated with a decrease in thalamocortical axons, a poor outgrowth of thalamic axons, and thalamocorticogenesis – this demonstrated that maternal antibiotic exposure in neonates could adversely impact fetal neurodevelopment.

Allergic lung inflammation in offspring is also strongly associated with prenatal antibiotic exposure. Induced anaphylaxis is found to be common in neonatal immune system development as a consequence of exposure to broad-spectrum ampicillin. In these instances, T regulatory cell deficiency (colonic regulatory T cells in particular) occurs as the immune system cannot generate CD4+ T cells. Dysregulated Th1 responses therefore occur.