Publisher Health

A research survey of primary school teachers in England has emphasised the importance of the relationship between parents and primary schools during lockdown school closures, with teachers providing a range of practical and emotional support alongside academic assistance to parents to try and negate perceived disadvantages in home circumstances.
With schools closed from March 2020 until the end of the academic year and again from January 2021, pupils were taught online. This put an expectation on parents to shoulder some of the responsibility in ensuring pupils were engaged in their learning and to try and minimise some of the disadvantages faced by pupils from lower income families who may not have had access to the same learning equipment or facilities as others.
Academics from Anglia Ruskin University (ARU) led a team of researchers who surveyed 271 primary school teachers from across the country during June and July 2000, and also carried out follow-up interviews with a smaller cohort in April this year to compare the second round of school closures from January 2021.
Participants worked in schools with differing levels of pupil premiums, which is additional funding provided by the Government to schools based on the number of pupils in a school deemed to be at an economic or social disadvantage. Lower pupil premium schools had fewer children considered to be at a disadvantage, while higher pupil premium schools had more.
The vast majority (84%) of teachers felt some pupils had been disadvantaged by school closures due to their home circumstances.
The researchers found that all teachers provided resources for parents to use at home, either created by themselves or using other sources. However, while pupils from schools with a lower pupil premium number were significantly better able to access all resources than those from schools with higher pupil premium numbers, middle income families struggled to find the time to engage with home schooling, with many working from home in white collar professions during the pandemic.

Researchers from Uppsala University have been able to document and visualise hearing loss-associated genes in the human inner ear, in a unique collaboration study between otosurgeons and geneticists. The findings illustrate that discrete subcellular structures in the human organ of hearing, the cochlea, are involved in the variation of risk of age-related hearing loss in the population. The study is published in BMC Medicine.
Hearing loss is a potentially debilitating condition that affects more than 1.23 billion people worldwide. The most common form of hearing loss, which represents 90% of all cases, is related to the degenerative effects of aging on hearing, i.e., age-related hearing loss or presbycusis. However, the molecular mechanisms that underlie the development of age-related hearing loss and individual variation in risk are poorly elucidated.
In the current study, a unique collaboration was established between otologists and geneticists at Uppsala University, which allowed for functional follow-up studies of candidate genes from genome-wide association studies (GWAS) using immunohistochemistry in the human cochlea.
“The cochlea, and in particular the hearing organ, the organ of Corti, is a highly vulnerable structure that is difficult to analyse since it is surrounded by the hardest bone in the body,” says Helge Rask-Andersen, MD and Senior Professor at the Department of Surgical Sciences. “We have been able to study some of the molecular components of human hearing that are critical for the conversion of sound to nerve electric impulses.”
Genetic variants at 67 genomic regions were found to contribute to increased risk of age-related hearing loss. Genome-wide association studies (GWAS) on hearing-related traits were performed in the UK Biobank, which has half a million participants from the United Kingdom. Genetic associations are difficult to interpret by themselves and follow-up experiments are often required before causal genes can be inferred.
“It is an amazing opportunity to be able to follow up our findings in human cochlear samples, since there are molecular differences between the hearing organ of humans and other mammals,” says Mathias Rask-Andersen, Associate Professor at the Department of Immunology, Genetics and Pathology.
Candidate proteins from GWAS were visualised with immunofluorescent antibodies and super-resolution structured illumination microscopy (SR-SIM) by Dr Wei Liu, MD and Associate Professor at the Department of Surgical Sciences. Several proteins were observed within the spiral ganglion, which contains the neuronal cell bodies that innervate the hair cells in the organ of Corti and carry neuronal impulses to the brain via the cochlear nerve.
The researchers could also visualise hearing loss-associated proteins in discrete subcellular domains in the hair cells for the first time in humans, such as TRIO and F-actin-binding protein (TRIOBP) in the hair tufts (stereocilia) and LIM domain only protein 7 (LMO7) in the cuticular plate, which is an actin-rich structure that anchors stereocilia to the cell body. The stereocilia are the microscopic or nano-sized ‘hairs’ that protrude from the hair cells of the organ of Corti. They respond to mechanical vibrations from sounds that reach us and are transferred and amplified from the ear drum to the inner ear by the small middle ear bones.
Taken together, the findings from the current study demonstrate that common genetic variations associated with age-related hearing loss affect the structures of the cochlea, in particular the neuronal processes of the spiral ganglion, but also structures directly involved in the transduction of mechanical stimuli to neuronal impulses. This knowledge may help to better understand the biological mechanisms that lead to age-related hearing loss and generate strategies for prevention such as novel pharmacological treatments.
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In research published in the journal Cell Systems, Professor Lenore Cowen of the Tufts Department of Computer Science and colleagues from Massachusetts Institute of Technology (MIT) collaborated to design a structurally-motivated deep learning method built from recent advances in neural language modeling. The team’s deep-learning model, called D-SCRIPT, was able to predict protein-protein interactions (PPIs) from primary amino acid sequences.
Those predictions allow researchers to model PPI networks with a clustering method and enable the detection of functional subnetworks, or modules. Scientists study organisms’ PPI networks as a means of understanding their signaling circuitry, which could lead to better prediction of cell behavior and gene functions, while finding functional modules in PPI networks could help researchers reach stronger understandings of cellular functional organization.
Cowen along with researchers Sam Sledzieski, Rohit Singh, and renowned computational biologist Bonnie Berger from MIT’s Computer Science and Artificial Intelligence Lab found that the D-SCRIPT model, trained on more than 38,000 human PPIs, was better able to generalize when compared to the current state-of-the-art approach (the deep-learning method PIPR), and therefore could characterize fly proteins. They also applied D-SCRIPT to screen for PPIs related to cow digestion and identified functional gene modules that related to immune response and metabolism.
The researchers concluded that the D-SCRIPT model trained on human PPI data could be applied to many species of interest — critically, even those that have been rarely studied or that lack PPI data.
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Cedars-Sinai researchers have found that blocking the action of a protein called interleukin 6 (IL-6), part of the immune system, could resolve the delirium that often accompanies urinary tract infection (UTI) in elderly patients. Their study in laboratory mice, published in the Journal of Neuroinflammation, could pave the way for clinical trials of IL-6 inhibitors as a treatment for UTI-associated delirium in humans.
Older women are among the most susceptible to developing UTIs, an infection of the bladder and urethra that causes urinary urgency and pain. UTIs also can cause delirium in older people, resulting in a sharp decline in mental abilities that triggers disoriented thinking.
“Up to one-third of elderly patients hospitalized with UTIs can experience some degree of confusion and reduced awareness of their surroundings,” said Shouri Lahiri, MD, director of the Neurosciences Critical Care Unit and Neurocritical Care Research at Cedars-Sinai and senior author of the study. “Delirium affects millions of patients a year in the U.S., contributing to longer hospital stays, long-term cognitive problems and increased mortality. Delirium can be a tipping point from which patients never fully recover. This is well established. What is less well established is why this is happening.”
To better understand the specific biological mechanisms behind UTI-associated delirium, Lahiri and colleagues observed laboratory mice with and without UTIs in specially designed mazes. In an arena where the animals could move about freely, uninfected mice spent more time in the center of the chamber. Those with UTIs huddled in the periphery, suggesting they had higher levels of anxiety, a common symptom of delirium.
In a Y-shaped maze with three arms to explore, uninfected mice tended to explore all three arms, while mice with UTIs kept returning to the same one, suggesting a lapse in short-term memory, another feature of delirium.
The investigators also observed structural changes in the brains of mice with UTIs.

PLOS. “For cardiovascular disease patients, more physical activity may be better, research suggests: Study suggests that health benefits of exercise may plateau for healthy individuals, but not heart disease patients.” ScienceDaily. ScienceDaily, 2 December 2021. .
PLOS. (2021, December 2). For cardiovascular disease patients, more physical activity may be better, research suggests: Study suggests that health benefits of exercise may plateau for healthy individuals, but not heart disease patients. ScienceDaily. Retrieved December 6, 2021 from www.sciencedaily.com/releases/2021/12/211202141458.htm
PLOS. “For cardiovascular disease patients, more physical activity may be better, research suggests: Study suggests that health benefits of exercise may plateau for healthy individuals, but not heart disease patients.” ScienceDaily. www.sciencedaily.com/releases/2021/12/211202141458.htm (accessed December 6, 2021).

Dengue, Chikungunya, and Zika viruses have all been recorded in Mexico; however, recent diagnostic advances have improved the accuracy of serological testing. A study publishing Dec. 2 in PLOS Neglected Tropical Diseases by José Esteban Muñoz-Medina at the Mexican Institute of Social Security, Mexico, and colleagues suggests that current estimates of the incidence of arboviruses in Mexico may have been previously underestimated.
Chikungunya and Zika virus were first detected in Mexico in 2014 and 2015, respectively. However, diagnostic techniques used by the National Network of Public Health Laboratories focused solely on the detection of Dengue virus until 2017. Prior to implementation of the new technique, the true incidence of these 3 arboviruses, as well as the incidence of coinfections was unknown. To determine the incidence of Dengue, Chikungunya and Zika in endemic areas of Mexico, researchers conducted a cross-sectional study of 1038 serum samples used to confirm the diagnosis of Dengue, chikungunya, or Zika during the first three years of co-circulation of these arboviruses. The researchers reanalyzed the serum samples using a test that could identify any of the three viruses in a single reaction.
The researchers found 2.4 times the rate of arbovirosis as originally reported, including coinfections, suggesting underestimation of the incidence of the three viruses. However, future research is needed to provide up-to-date incidence estimates of each virus.
According to the authors, “The information generated in this study enriches the country with more precise epidemiological information on these arboviruses, which can help improve estimates of burden, morbidity and resource allocation, as well as providing information to design better diagnostic algorithms, given the possible scenario of new outbreaks or epidemics caused by these or other arboviruses that are currently circulating in the Americas.”
Muñoz-Medina adds, “We studied the circulation of two new arboviruses in a Dengue endemic area to assess the impact on their circulation and underestimation of cases.”
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Pigtailed macaques are a candidate model organism for two hemorrhagic diseases of public health concern: Kyasanur Forest disease and Alkhurma hemorrhagic disease, report Rebecca Broeckel at the National Institutes of Health in Montana, and colleagues, in a study publishing Dec. 2 in the open-access journal PLOS Pathogens.
Tick-borne flaviviruses such as Kyasanur Forest disease virus (KFDV) in India, and its close relative Alkhurma hemorrhagic disease virus (AHFV) in the Arabian Peninsula, cause severe hemorrhagic fever in humans, and infection can be fatal. Their increasing prevalence and geographic spread pose a public health threat, but an absence of close animal models has hampered research and currently, vaccines against these tick-borne viruses have limited efficacy. In search of an accurate primate model for clinical research, researchers inoculated eight female pigtailed macaques (Macaca nemestrina) with KFDV and four with AHFV, and found that, like humans, they developed loss of appetite, dehydration, and hemorrhagic symptoms within two to four days. Infected macaques also exhibited reduced levels of blood lymphocytes and platelets, and elevated liver enzymes — hallmark symptoms of human KFDV infections. Infectious virus was found in the gastrointestinal tract, consistent with symptoms such as vomiting, diarrhea and hemorrhaging often seen in human patients. RNA sequencing of the whole blood transcriptome at zero, two, and six days after inoculation revealed that KFDV infection caused downregulation of gene expression for blood clotting factors, which may explain the greater severity of this disease compared to AHFV.
This study is the first to characterize infection of pigtailed macaques with KFDV or AHFV. The authors say that the similarity of pigtailed macaques’ symptoms to humans and their availability in clinical research make the species a strong candidate for future vaccine and antiviral research on these diseases of public health concern.
“Kyasanur forest disease virus (KFDV) is an emerging public health threat in India that causes hemorrhagic fevers in humans after the bite of infected tick, but it is not clear how this virus causes disease,” the authors add. “Our work describes a new animal model of KFDV hemorrhagic fever that closely resembles human disease. This work reveals specific mechanisms of disease that can be targeted by drugs to treat severe infections.”
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Vaccines are effective in decreasing hospitalization and deaths from COVID-19 infection but the emergence of viral variants of concern may diminish their efficacy. A study publishing Dec. 2 in PLOS Pathogens by Emma Thomson, Brian Willett, and colleagues at the MRC-University of Glasgow Centre for Virus Research, United Kingdom and colleagues suggests that COVID-19 Delta variant may be more successful at evading the protective response of vaccines.
Mutations change the shape of the COVID-19 spike protein, preventing antibody recognition and enabling the virus to escape vaccine-induced immunity; however, the extent to which vaccine recipients are immune from the Delta variant is unknown. To quantify the capacity of different variants (Alpha, Beta and Delta) to evade protective immune response in vaccines, researchers analyzed serum samples collected from healthy people who had received either the Pfizer or Astra Zeneca vaccine. 156 people had received two doses and 50 people had received one dose. They exposed SARS-CoV-2 proteins in a virus model system to sera from vaccinated people and observed the antibody response, measuring how effectively antibodies prevented each variant from infecting cells (virus neutralization).
The researchers found that vaccines conferred protection from all COVID-19 variants but noted reduced antibody neutralization of both the Beta and Delta variants. Across all vaccinated individuals, the Delta variant reduced the immune response in recipients of both the Pfizer and Astra Zeneca vaccine 4.31 and 5.11-fold respectively. The study was not designed to measure vaccine efficacy directly, although it was in keeping with recent findings from Public Health England of slightly lower vaccine effectiveness against the Delta variant than previous variants. It also did not report on serological study of people who received the Moderna or Johnson & Johnson vaccines.
According to the authors, “While vaccines remain highly effective at preventing severe infection and death, ongoing monitoring of neutralization against new variants alongside studies of vaccine effectiveness are indicated as the virus continues to evolve over time, especially in vulnerable groups. Booster vaccines reduce the chance of being infected with currently circulating new variants. Newer updated vaccine designs are also likely to be required in time to prevent productive infection with newer variants of the virus.”
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In their publication in Science, Professor Guojun Sheng (Kumamoto University, Japan), Professor Alfonso Martinez Arias (Universidad Pompeu Fabra, Spain) and Professor Ann Sutherland (University of Virginia Health System, USA) offer a phylogenetic and ontogenetic overview of the primitive streak and its role in mediating amniote (vertebrate animals that develop on land) gastrulation, and discuss the implications of embryonic stem cell-based models of early mammalian embryogenesis on the function of this structure.
Most animals are bilaterally symmetrical and are organized using two basic coordinate systems. The first gives cells spatial identities along the anteroposterior (head-to-tail) and dorsoventral (back-to-front) axes. The second organizes cells into groups (i.e., germ layers). In most animals, including humans, there are three germ layers: the ectoderm (source of the skin, nervous system, eyes, etc.), the mesoderm (source of the muscles, bones, vessels, etc.) and the endoderm (source of the intestines, lungs, liver, pancreas, etc.). One of the most critical periods of development happens when a small number of pluripotent and dividing cells initiate the differentiation process in these two coordinate systems. In human development, this occurs at approximately two weeks after fertilization through a process called gastrulation and is associated with an embryonic structure called the primitive streak — a structure in early development that initiates bilateral symmetry and germ layer formation. Like water flowing down the side of a mountain, a gastrulating cell embarks on a journal of no return, culminating in its terminal differentiation into one of several hundred cell lineages that make up human tissues and organs.
With technical breakthroughs in rejuvenating differentiated cells back into a naïve state pioneered by scientists like John Gurdon and Shinya Yamanaka (2012 Nobel Prize winners), researchers worldwide are now able to grow pluripotent, pre-gastrulation human (and other mammalian) cells in the lab, and through stepwise addition of biochemical cues, guide these cells to differentiate into any one of hundreds of cell lineages. However, cultivating these cells into functioning tissues or organs has rarely been successful. One reason for this failure is that organogenesis (the process of organ formation) in vivo starts immediately after gastrulation when cells of different germ layer origins and spatial coordinate identities cooperate in making rudimentary organs. Through subsequent reciprocal interactions, these cells undergo organ- and species-specific proliferation, three-dimensional organization, and terminal differentiation before reaching functional maturity. Reproducing (recapitulating) such organ rudiments in vitro therefore has become the holy grail in stem cell biology and regenerative medicine research.
Achieving this would require recapitulation of gastrulation and its associated primitive streak. However, neither gastrulation nor the primitive streak has been rigorously analyzed in human development, and comparative views of animal gastrulation and the primitive streak in the literature are often incorrectly portrayed. Now, though a systematic review of previous research, Prof. Sheng and colleagues provide evidence that the primitive streak is not a conserved feature in amniote development, and that mammalian and avian primitive streaks evolved independently, utilizing different supra-cellular mechanisms that lead to their morphological emergence. The researchers stress that, in addition to mediating the emergence of germ layers from the epiblast (pluripotent cells), the main role of gastrulation is to confer newly formed cells in each germ layer a coordinate system to organize primary cell fates and the primordia of organs and tissues that are relative to each other spatially. Their analyses of different biomechanical parameters between various in vivo and in vitro models predict that a rudimentary mammalian body plan can form in the absence of a primitive streak. They also suggest that the “14-day rule” (where a human embryo cannot be cultured 14 days past fertilization or after the appearance of the primitive streak), which is currently used in many countries as the key ethical oversight in human embryological research, should be re-assessed and an alternative landmark be selected through a consensual discussion between different stakeholders to ensure scientific and ethical rigor.
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Omicron is the 13th variant of the Covid-19 virus to receive a Greek name under the World Health Organization’s classification system for variants of interest or concern.But how do you pronounce it? BBC Health Correspondent Laura Foster and archaeologist Gillian Hovell try to explain.