Culture

Bottom Line: Among women participating in cervical cancer screening in Sweden, those with a diagnosis of invasive cervical cancer had an increased risk of iatrogenic injuries (as a consequence of medical intervention) and non-iatrogenic injuries (caused by accidents and self-harm) requiring hospitalization.

Journal in Which the Study was Published: Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research

Author: Qing Shen, PhD, researcher in the Department of Medical Epidemiology and Biostatistics at the Karolinska Institutet in Stockholm

Background: “Cervical cancer screening is one of the most successful cancer prevention programs which has greatly reduced cervical cancer incidence and mortality,” said Shen. “Despite these substantial benefits, our research indicates that women with invasive cervical cancer experienced medical complications and psychological stress during their diagnostic workup, although at a very low level.”

Previous work conducted by Shen and colleagues demonstrated an increased risk of injuries during the time period before and after a diagnosis of any cancer. “These injuries were likely a result of invasive procedures and the severe psychological distress experienced during the clinical evaluation of a potential cancer,” Shen explained. Whether there is a similar increase in risk among patients screened for cervical cancer, when an organized cancer screening program was largely accessible, was unknown, she added.

How the Study was Conducted: Using data from the Swedish Total Population Register, the researchers identified over 3 million women who participated in cervical cancer screening during 2001-2012. Cross-linkage with multiple Swedish registries allowed for the identification of women within this cohort who received a diagnosis of invasive cervical cancer, cervical cancer precursor lesions, or had a normal smear during follow-up. The final cohort included roughly 1.85 million women with a normal smear, roughly 22,000 women with cervical intraepithelial neoplasia (CIN) grade 1, roughly 21,000 women with CIN2, roughly 37,000 with CIN3/adenocarcinoma in situ (AIS), and roughly 5,000 women with invasive cervical cancer.

The researchers examined the incidence of injuries during the diagnostic workup of patients who participated in cervical cancer screening. Among women with precursor lesions or cervical cancer, the diagnostic workup was defined as the time interval between the first Pap smear or punch biopsy until surgical treatment, or two months after the last smear or punch biopsy, if not treated surgically. Among women with normal smear results, the diagnostic workup was defined as the two months following the smear.

The researchers calculated incidence rates of both iatrogenic injuries and non-iatrogenic injuries that occurred during the diagnostic workup. Iatrogenic injuries, which were mostly related to receipt of a punch biopsy, and which required at least two days of hospitalization, were included in this analysis. Non-iatrogenic injuries, which included accidents and intentional self-harm, and which required at least one day of hospitalization, were included. Incidence rate ratios for injuries that occurred during the diagnostic workup, which were calculated by comparing women with a diagnosis of cervical cancer or its precursor lesions with women with a normal smear, were adjusted for age, calendar period, screening adherence, education, income, and marital status.

Results: Compared with women with a normal smear, women with a diagnosis of invasive cervical cancer had eight times the incidence of iatrogenic injuries, and women with CIN3/AIS had three times the incidence of iatrogenic injuries. Women with CIN1-2 did not have a significantly increased rate of iatrogenic injuries compared with women with a normal smear.

“Women with invasive cancer can have greater vascularity due to tumor growth, which can lead to hemorrhage and hematoma following a biopsy,” Shen explained.

Compared with women with a normal smear, women with a diagnosis of invasive cervical cancer had about twice the incidence of non-iatrogenic injuries. Women with CIN1-2, CIN3, or AIS did not have a significantly increased rate of non-iatrogenic injuries compared with women with a normal smear. The most common type of non-iatrogenic injuries were unintentional falls, Shen said.

“An increase in non-iatrogenic injuries points to high levels of psychological distress in relation to receiving a diagnosis of cervical cancer,” said Shen.

Author’s Comments: “This study for the first time systematically examined the risks of injuries during the cervical diagnostic workup. Although the chance of having such injuries was rare, we found an increased risk of inpatient care for iatrogenic and non-iatrogenic injuries for women with invasive cervical cancer. It is important to emphasize, however, that cervical cancer screening is greatly beneficial for the early detection of cancer and is largely safe.”

Study Limitations: Limitations of the study include a lack of information on non-surgical treatments among women with invasive cervical cancer, such as palliative care, chemotherapy, and radiotherapy, which could have potential implications for injuries. Further, because the authors only included iatrogenic injuries that required at least two days of inpatient care, only the more severe forms of these injuries were captured in this analysis.

Funding & Disclosures: The study was sponsored by the Swedish Cancer Society; the Swedish Research Council for Health, Working Life and Welfare; a Karolinska Institutet Senior Researcher Award and Strategic Research Area in Epidemiology Award; and by the China Scholarship Council.

Shen declares no conflict of interest.

What The Study Did: Researchers examined the sociodemographic characteristics of patients associated with racial/ethnic differences in COVID-19 outcomes.

Authors: Bhramar Mukherjee, Ph.D., of the University of Michigan School of Public Health in Ann Arbor, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2020.25197)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

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WEST LAFAYETTE, Ind. -- Getting run over by a car is not a near-death experience for the diabolical ironclad beetle.

How the beetle survives could inspire the development of new materials with the same herculean toughness, engineers show in a paper published Wednesday (Oct. 21) in Nature.

These materials would be stiff but ductile like a paper clip, making machinery such as aircraft gas turbines safer and longer-lasting, the researchers said.

The study, led by engineers at the University of California, Irvine (UCI) and Purdue University, found that the diabolical ironclad beetle's super-toughness lies in its two armorlike "elytron" that meet at a line, called a suture, running the length of the abdomen.

In flying beetles, the elytra protect wings and facilitate flight. But the diabolical ironclad beetle doesn't have wings. Instead, the elytra and connective suture help to distribute an applied force more evenly throughout its body.

"The suture kind of acts like a jigsaw puzzle. It connects various exoskeletal blades - puzzle pieces - in the abdomen under the elytra," said Pablo Zavattieri, Purdue's Jerry M. and Lynda T. Engelhardt Professor of Civil Engineering.

This jigsaw puzzle comes to the rescue in several different ways depending on the amount of force applied, Zavattieri said. A video explaining these findings is available on YouTube at https://youtu.be/NS3AqJB5SfU.

To uncover these strategies, a team led by UCI professor David Kisailus first tested the limits of the beetle's exoskeleton and characterized the various structural components involved by looking at CT scans.

Using compressive steel plates, UCI researchers found that the diabolical ironclad beetle can take on an applied force of about 150 newtons - a load of at least 39,000 times its body weight - before the exoskeleton begins to fracture.

That's more impressive than sounds: A car tire would apply a force of about 100 newtons if running over the beetle on a dirt surface, the researchers estimate. Other terrestrial beetles the team tested couldn't handle even half the force that a diabolical ironclad can withstand.

Zavattieri's lab followed up these experiments with extensive computer simulations and 3D-printed models that isolated certain structures to better understand their role in saving the beetle's life.

All of these studies combined revealed that when under a compressive load such as a car tire, the diabolical ironclad beetle's jigsaw-like suture offers two lines of defense.

First, the interconnecting blades lock to prevent themselves from pulling out of the suture like puzzle pieces. Second, the suture and blades delaminate, which leads to a more graceful deformation that mitigates catastrophic failure of the exoskeleton. Each strategy dissipates energy to circumvent a fatal impact at the neck, where the beetle's exoskeleton is most likely to fracture.

Even if a maximum force is applied to the beetle's exoskeleton, delamination allows the interconnecting blades to pull out from the suture more gently. If the blades were to interlock too much or too little, the sudden release of energy would cause the beetle's neck to snap.

It's not yet known if the diabolical ironclad beetle has a way to heal itself after surviving a car "accident." But knowing about these strategies could already solve fatigue problems in various kinds of machinery.

"An active engineering challenge is joining together different materials without limiting their ability to support loads. The diabolical ironclad beetle has strategies to circumvent these limitations," said David Restrepo, an assistant professor at the University of Texas at San Antonio who worked on this project as a postdoctoral researcher in Zavattieri's group.

In the gas turbines of aircraft, for example, metals and composite materials are joined together with a mechanical fastener. This fastener adds weight and introduces stress that could lead to fractures and corrosion.

"These fasteners ultimately decrease the performance of the system and need to be replaced every so often. But the interfacial sutures of the diabolical ironclad beetle provide a robust and more predictable failure that could help solve these problems," said Maryam Hosseini, who worked on this project as a Ph.D. student and postdoctoral researcher in Zavattieri's group. Hosseini is now an engineering manager at Procter & Gamble Corp.

UCI researchers built a carbon fiber composite fastener mimicking a diabolical ironclad beetle's suture. Purdue researchers found through loading tests that this fastener is just as strong as a standard aerospace fastener, but significantly tougher.

"This work shows that we may be able to shift from using strong, brittle materials to ones that can be both strong and tough by dissipating energy as they break. That's what nature has enabled the diabolical ironclad beetle to do," Zavattieri said.

LOS ANGELES -- An estimated 5.5 million people in the United States live with Alzheimer's disease, which is the most common form of dementia.

Keck Medicine of USC is enrolling individuals in an international phase 3 clinical trial to examine the safety and effectiveness of deep brain stimulation to treat Alzheimer's. The study uses electrical impulses to stimulate the region of the brain known as the fornix, which is associated with memory and learning.

"Deep brain stimulation has successfully treated conditions such as Parkinson's disease by improving motor skills, and we are now investigating if this therapy can stabilize or improve cognitive function," says Darrin Lee, MD, PhD, a neurosurgeon with Keck Medicine of USC and the site's principal investigator of the study. "Based on the results of earlier phases of this clinical trial, the treatment offers a potential benefit for patients with mild Alzheimer's."

This randomized, double-blind study will last four years. Subjects will first take a standardized assessment test for Alzheimer's to be used as a baseline measure of cognitive ability throughout the study.

Next, researchers will implant electrodes into subjects' brains that connect to a battery pack, similar to a heart pacemaker, placed underneath the collarbone.

For the first year of the study, subjects will be given either low-frequency stimulation to the brain, high-frequency stimulation or a placebo -- no stimulation.

"For those with Alzheimer's disease, certain parts of the brain become atrophied," Lee says. "We are testing to see if stimulating the brain's fornix can reawaken brain activity in this area and stop the progression of the disease."

During the first year, subjects will be given subsequent cognitive tests to check if their memory or learning skills have held steady or improved. At the end of the year, study researchers will examine data to determine which level of stimulation had the most impact on these skills.

For the next three years of the trial, all subjects in the study will receive what researchers have determined is the optimal frequency of deep brain stimulation, even those originally receiving the placebo. Patients will continue to be given cognitive assessments throughout the four-year period.

To qualify for the trial, patients must be 65 or older, have been diagnosed with mild Alzheimer's and take Alzheimer's medication, and have a caregiver or family member who can accompany them to doctor visits.

The clinical trial involves approximately 200 patients at some 20 sites in the United States, Canada and Germany. Keck Medicine plans to enroll 8-15 patients.

The trial is sponsored by Functional Neuromodulation, Inc.

Those interested in enrolling in the clinical trial with Keck Medicine can contact Amanda Romano at amanda.romano@med.usc.edu or 213-393-5640.

Opioid use disorder affects about 2 million Americans each year and is the No. 1 cause of accidental death. Between 50 to 90 percent of individuals with this disorder were exposed to a prescription opioid first. Opioid use disorder is likely underdiagnosed within the healthcare system setting, which may be due in part to the reticence of practitioners who lack the specialized training in addiction medicine.

A new, retrospective cross-sectional study by researchers from Florida Atlantic University's Schmidt College of Medicine in collaboration with Geisinger, the University of Pennsylvania Perelman School of Medicine, and Cooper Medical School of Rowan University, shows that information in electronic health records (EHRs) may help identify patients with opioid use disorder. EHRs provide significant patient information such as demographic features, prior health encounters and prescription history.

For the study, researchers analyzed individuals within Geisinger, a large, integrated health system in Pennsylvania, who were prescribed opioids between Dec. 31, 2000 and May 31, 2017, using a mixed-methods approach. The cohort was identified from 16,253 patients enrolled in a Geisinger-specific medication monitoring program for opioid use, including patients who maintained or violated contract terms, as well as a demographically matched control group of 16,253 patients who were prescribed opioids but not enrolled in the monitoring program. Substance use diagnoses and psychiatric comorbidities were assessed using automated EHR summaries. A manual medical record review procedure using the Diagnostic and Statistical Manual of Mental Disorders, DSM-5 (Fifth Edition) criteria for opioid use disorder was completed for a subset of patients.

Results of the study, published in JAMA Network Open, suggest that patients with opioid use disorder may be identified using information available in the EHR, even when diagnostic codes do not reflect this diagnosis. Furthermore, the study demonstrates the utility of proxies coding for DSM-5 criteria from medical records to generate a quantitative DSM-5 score that is associated with opioid use disorder severity. Methods used in the study are unique in deriving a severity score that aims to mirror severity scores from more traditional interview-based diagnostic procedures.

Among the 16,253 patients enrolled in the medication monitoring program, opioid use disorder diagnoses as defined by ICD-10 diagnostic codes in the EHRs were present at a much lower rate than expected from the published literature - 291 patients (2 percent) - indicating the necessity for alternative diagnostic strategies. Using proxy measurements from the EHR for the DSM-5 criteria to assess opioid use disorder, the manual review of 200 patients in the monitoring program and 200 control patients pinpointed a larger percentage of patients with moderate-to-severe opioid use disorder. In the monitoring program, researchers identified 145 of 200 (73 percent) and in the control group 27 of 200 (14 percent) compared with the lower prevalence of opioid use disorder assessed using diagnostic codes.

"We find that chart review of electronic health records enables us to identify more patients with probable opioid use disorder than relying on diagnostic codes alone," said Vanessa Troiani, Ph.D., senior author and an assistant professor at Geisinger, who directed the team of scientists involved in this research.

Typically, opioid use disorder is diagnosed during a patient-physician consultation during which the addiction trained practitioner uses dialogue with the patient or questionnaires to evaluate whether the patient exhibits symptoms of opioid use disorder based on the DSM-5 opioid use criteria. These criteria are based on the assessment of whether opioid use causes significant impairment in physical and social functioning, as well as aspects of craving and unsuccessful efforts to reduce or control use, with multiple DSM-5 criteria within a 12-month period warranting an opioid use disorder diagnosis. In addition, the practitioner often relies on the self-report of the patient but may consult a significant other or relative of the patient.

"Our study showed that proxy measures that rely on multiple sources of data, including prescription drug history and notes in the electronic health record, may help identify patients with opioid use disorder who have not received a diagnosis," said Janet Robishaw, Ph.D., co-author, senior associate dean for research and chair of the Department of Biomedical Sciences in FAU's Schmidt College of Medicine.

Sarah Palumbo, 21, first author and a second-year medical student in FAU's Schmidt College of Medicine played a lead role in the research. Palumbo, who works in Robishaw's laboratory, was one of the first students accepted into the "FAU High School M.D. Direct" program and graduated from college three months after graduating from FAU High School.

"Our findings that psychiatric and other substance use codes are increased in patients in the drug monitoring program suggest the potential for assessing psychiatric and other substance use codes as an associated factor to evaluate patient risk for opioid use disorder in the chronic pain setting," said Palumbo.

According to the National Institute on Drug Abuse, roughly 21 to 29 percent of patients prescribed opioids for chronic pain misuse them and between 8 and 12 percent develop an opioid use disorder. An estimated 4 to 6 percent who misuse prescription opioids transition to heroin. This issue has become a public health crisis with devastating consequences including increases in opioid misuse and related overdoses, as well as the rising incidence of neonatal abstinence syndrome due to opioid use and misuse during pregnancy.

"Opioids continue to be used for the treatment of pain. Precision medicine within integrated health systems such as Geisinger could be a major associated factor in developing more efficient pain treatments with less risk for addiction, and studies of this potential could be helped by establishing more effective proxy measures for opioid use disorder using data from electronic health records," said Robishaw.

A gut hormone, ghrelin, is a key regulator of new nerve cells in the adult brain, a Swansea-led research team has discovered. It could help pave the way for new drugs to treat dementia in patients with Parkinson's Disease.

Blood-borne factors such as hormones regulate the process of brain cell formation - known as neurogenesis - and cognition in adult mammals.

The research team focused on the gut hormone acyl-ghrelin (AG), which is known to promote brain cell formation. A structure change to the hormone results in two distinct forms: AG and unacylated-ghrelin (UAG).

The team, led by Dr Jeff Davies of Swansea University Medical School, studied both AG and UAG to examine their respective influences over brain cell formation.

This research is relevant to Parkinson's as a large proportion of those with the disease experience dementia, which is linked to a loss of new nerve cells in the brain. This loss leads to a reduction in nerve cell connectivity, which plays a vital role in regulating memory function.

The team's key overall findings were:

the UAG form of ghrelin reduces nerve cell formation and impairs memory

Individuals diagnosed with Parkinson's disease dementia have a reduced AG:UAG ratio in their blood

Dr Jeff Davies of Swansea University Medical School, lead researcher, said:

"Our work highlights the crucial role of ghrelin as a regulator of new nerve cells in the adult brain, and the damaging effect of the UAG form specifically.

This hormone represents an important target for new drug research, which could lead ultimately to better treatment for people with Parkinson's.

Our findings show that the AG:UAG ratio could also serve as a biomarker, allowing earlier identification of dementia in people with Parkinson's disease."

The team included collaborators from Newcastle University (UK) and Monash University (Australia). They examined the role of AG and UAG in the brain, and also compared blood collected from Parkinson's disease patients diagnosed with dementia with cognitively intact PD patients and a control group.

They found:

Higher levels of UAG, using both pharmacological and genetic methods, reduced hippocampal neurogenesis and brain plasticity.

AG helped reverse spatial memory impairments

UAG blocks the process of brain cell formation prompted by AG

The Parkinson's patients with dementia were the only one of the three patient groups examined to show a reduced AG:UAG ratio in their blood.

The research was published in Cell Reports Medicine.

Marine fish species are migratory in nature and not respectful of human-made territorial boundaries, which represents a challenge for fisheries management as policies tend to focus at the national level. With an average catch of 48 million tonnes per year, and USD $77 billion in annual fishing revenue, these species support critical fisheries, and require international cooperation to manage, according to UBC research.

The researchers focused on fish species that cross the Exclusive Economic Zones (EEZs) of two or more coastal states which are most often targeted by fisheries operating within those EEZs. They identified over 633 exploited transboundary species worldwide and found that the catch and revenue from these fisheries had been severely underestimated and over-exploited.

"We found that some countries get over 80 per cent of their catch from transboundary species. These are not small numbers or small nations: these catches are specifically important in terms of revenue for Northern America and Eastern Asia," said Juliano Palacios Abrantes, a doctoral student in UBC's Institute for the Oceans and Fisheries, and lead author on the study. "Fishing nations such as China, the USA, Russia, Peru, and Japan alone are responsible for 41 per cent of the yearly global fisheries revenue from transboundary species."

"Fisheries that include transboundary fish species, such as anchoveta in Peru's transboundary area with Chile or pollock in the U.S., Russia and Japan transboundary Alaskan region, catch on average 48 million tonnes per year, or USD $77 billion in annual fishing revenue," said William Cheung, senior author and professor in in UBC's Institute for the Oceans and Fisheries. "The catch from these fish species are declining at a much higher rate than non-transboundary species."

There are agreements between countries in many of these EEZs. Peru and Chile recently signed an agreement towards standardizing stock assessments and management of the southern anchoveta stock. However, transboundary fisheries have led to some notorious fisheries-related conflicts, including those between those Canada, the USA, Russia, and the European Union. The EU, Norway, Iceland, and Denmark's Faroe Islands continue to be at odds over the allowable catch sizes for Atlantic mackerel, a transboundary fish species that has changed its distribution patterns due to climate change.

"Climate change is going to continue changing the distribution of fish stocks among countries, with some new transboundary species emerging and some disappearing," said Palacios Abrantes. "This can only lead to more difficulties if nations are not able to adapt and manage fisheries through effective international cooperation."

"Collaborations are going to be needed to maximize long?term ecological, social, and economic benefits of shared marine species, particularly as stocks decline due to overfishing, and as fish populations move about the ocean in different patterns due to climate change," said Cheung. "Nations will have to adapt to these anthropogenic changes in our world as quickly, if not quicker, than fish species are having to do."

FGFR2 and gastric cancer

Fibroblast growth factor receptor 2 is a protein that aids in the growth of new cells. So, for example, FGFR2 helps repair injuries by aiding in the growth of new tissue cells in the affected area. What FGFR2 does not do however, is tell cells to stop growing. FGFR2 is like a mindless robot that does the same job over and over again, even if that job is no longer needed. This means sometimes FGFR2 continues churning out new cells beyond their need, i.e. even after the injured area has been repaired, at which point these cells form tumors and turn into cancer. When the tumor saps all the resources from its surroundings, FGFR2 is activated and new cancer cells are sent down the bloodstream to areas with untapped resources. An "overexpression" of FGFR2 may mean this protein has been activated to make cells to cancerous levels, evidenced in FGFR2 overexpression having a reported 3-10% association with gastric cancers.

Why "in the blood" matters

Cancer has "heterogeneity" in that it may differ in nature between the primary site and the site of recurrence and metastasis. This makes tracking cancer a game of cat and mouse with a blindfold on. Unless you have access to the molecular structure of the cells passing through the bloodstream, you cannot see where the cancer has spread until its fledgling cells have settled into a new area and grown into an obtrusive tumor.

"If circulating cancer cells in the blood can be detected, it will be possible to investigate the characteristics of cancer metastases that are rarely removed, and it will be a useful diagnostic method for selecting molecular-targeted therapeutic agents suitable for the characteristics of each patient's unique form of cancer", says lead researcher Masakazu Yashiro, Department of Molecular Oncology and Therapeutics, Graduate School of Medicine, Osaka City University. With his team, they measured the FGFR2 expression level of circulating tumor cells with a FACScan on a 2ml sample of blood periphery to a tumor they had previously assessed the FGFR2 expression level via immunohistochemistry. They found that FGFR2 overexpression in the blood samples was significantly correlated to the FGFR2 expression level of the tumor.

"The significantly poorer relapse-free survival of patients with these higher correlations suggests that with this new method of finding FGFR2-positive cancer cells in the bloodstream, scientists can target an existing tumor quicker and with more accurate therapeutic agents", adds Masakazu. "Inhibitors targeting FGFR2 abnormalities are under development. By successfully identifying FGFR2-expressing cancer cells with a small amount of blood, we expect this tool to contribute to appropriate decision-making on the use of anticancer drugs, such as determining when to start FGFR inhibitors."

In school bullying, there are people who are chronic victims. The acts of aggression that they experience are not limited to a particular moment or period of time, but rather part of a sustained process over a long period of time. These aggressions have much more serious consequences: chronic victims show higher levels of stress and personality issues that do not appear in students who have no connection to school bullying or those who have experienced it for shorter periods of time.

Studies on bullying tend to analyze the variables that influence the victimization of certain people but usually overlook the variable of time, which is an important factor in order to understand the processes that a person who is constantly a victim of intimidation and aggression undergoes. A University of Cordoba research team wanted to study how levels of popularity, acceptance and friendship vary over time depending on if the victims are sporadic, chronic or experience varying degrees of bullying.

"There were several questions we came up with. Does being a victim for a prolonged period of time lead to deteriorated peer relationships? Does improving social status and friendship with schoolmates help to break free from victimization?" explains Eva Romera, researcher on the study along with researchers Rosario Ortega, Ana Bravo and Carmen Jiménez. This research study is part of the project "Social and moral competence and peer group ecology in violence among schoolchildren: a longitudinal and transactional study", coordinated by Eva Romera. This project aims to analyze how the dynamics between social, motivational and moral factors develop in peer groups in relation to bullying and cyberbullying.

The study is particularly relevant in preteen and teenage years, stages when the relationships between friendship, acceptance and visibility within the group acquire greater prominence and when there is greater vulnerability in terms of bullying. Questionnaires were given out at three different moments: the first in October 2017, the second in May 2018 and the third in October 2018. In total, 1346 students participated who, when data was first gathered, were in fifth grade (primary school), seventh grade (secondary school) and ninth grade (secondary school) at 22 different schools in the province of Cordoba. Among the students who took part in the study, 38.80% had been victims of school bullying by their schoolmates at some time. Of those, 64.4% were categorized as sporadic victims, 26.8% as victims of varying degrees and 8.8% as chronic victims.

The results verified that, in each class, people take on roles and positions in a social hierarchy that tend to remain fixed for some time, making it difficult for victims to break free from this destructive pattern of domination and submission. This could explain why bullying can be prolonged over time and create chronic victims. These results support the idea that a key intervention tactic in these situations could be trying to break down those social structures that become toxic in the classroom.

As far as sporadic victims and victims of varying degrees, these had stable levels of acceptance, popularity and friendship over time. However, in the case of chronic victims, these levels decreased, meaning that as victimization becomes chronic, people are viewed as less popular by the others and they lose friendships with them. This situation of rejection and isolation that victims undergo is exacerbated and makes it difficult for the victim to find opportunities to break free from the bullying by themselves. This demonstrates that maintaining quality friendships could act as a protective factor against bullying.

"The results of this study suggest that the stabilization of the victimization of a person at school has highly negative social repercussions and requires prevention and intervention measures in order to remedy not only the effects associated with this process, but also the conditioning factors that reinforce the act of subjecting certain children to being isolated from and rejected by their schoolmates", explains Romera.

The aim of this study is to raise awareness among the educational community, especially among educators, on the crucial role that they must perform to prevent behaviors of rejection suffered by victims as well as pointing out their role as a guide in the management of group relations. The results emphasize that fostering a friendly atmosphere among children in the classroom, as well as promoting the development of social, moral and emotional competences, are key to preventing school bullying. All this can be done using resources that favor dialog, conflict resolution, cooperation and free expression of opinions as a positive way to manage social relations.

(Vienna, 21 October 2020) A recent study conducted by a research team led by Florian Kiefer from MedUni Vienna's Division of Endocrinology and Metabolism shows that cold ambient temperatures increase vitamin A levels in humans and mice. This helps convert "bad" white adipose tissue into "good" brown adipose tissue which stimulates fat burning and heat generation. This "fat transformation" is usually accompanied by enhanced energy consumption and is therefore considered a promising approach for the development of novel obesity therapeutics. The study has now been published in the leading journal Molecular Metabolism.

In humans and mammals, at least two types of fatty depots can be discerned, white and brown adipose tissue. During obesity development, excess calories are mainly stored in white fat. In contrast, brown fat burns energy and thereby generates heat. More than 90% of the body fat depots in humans are white which are typically located at the abdomen, bottom, and upper thighs. Converting white into brown fat could be a new therapeutic option to combat weight gain and obesity.

A research group led by Florian Kiefer from the Division of Endocrinology and Metabolism, Department of Medicine III at MedUni Vienna demonstrated now that moderate application of cold increases the levels of vitamin A and its blood transporter, retinol-binding protein, in humans and mice. Most of the vitamin A reserves are stored in the liver and cold exposure seems to stimulate the redistribution of vitamin A towards the adipose tissue. The cold-induced increase in vitamin A led to a conversion of white fat into brown fat ("browning"), with a higher rate of fat burning.

When Kiefer and his team blocked the vitamin A transporter "retinol-binding protein" in mice by genetic manipulation, both the cold-mediated rise in vitamin A and the "browning" of the white fat were blunted: "As a consequence, fat oxidation and heat production were perturbed so that the mice were no longer able to protect themselves against the cold," explains Kiefer. In contrast, the addition of vitamin A to human white fat cells led to the expression of brown fat cell characteristics, with increased metabolic activity and energy consumption.

"Our results show that vitamin A plays an important role in the function of adipose tissue and affects global energy metabolism. However, this is not an argument for consuming large amounts of vitamin A supplements if not prescribed, because it is critical that vitamin A is transported to the right cells at the right time," explains the MedUni Vienna researcher. "We have discovered a new mechanism by which vitamin A regulates lipid combustion and heat generation in cold conditions. This could help us to develop new therapeutic interventions that exploit this specific mechanism."

Volunteers from the Catholic Church in Brazil helped to mitigate the impact of COVID-19 among the elderly, a new study shows.

Peter Kevern, Professor Values in Health and Social Care at Staffordshire University, partnered with The Pontifical Catholic University of São Paulo to carry out the study which looked at the contribution of the Pastoral da Pessoa Idosa (PPI) programme in Brazil.

And Professor Kevern suggests that the study findings may well assist the UK whose social care system has been severely tested during the pandemic.

PPI is a volunteer movement that uses the organisational structure of the Catholic Church of Brazil to provide a range of support to isolated elderly people right across the country. Anyone can be a volunteer in their community or in their building to support older people through the scheme.

Last year, approximately 25,000 'Pastoral Agents', provided home visits, personalised practical help and support to 164,000 older people. Pastoral Agents are also trained to measure and report indicators of wellbeing such as fragility, fluid intake, annual flu vaccination, and to refer people to government agencies.

Professor Kevern explained: "Brazil has a fragile social infrastructure so there are many unmet social needs to be addressed. The aim of this research was to estimate the contribution of the PPI programme to the health and social support of older people. Almost 4,000 volunteers were interviewed over a one-week period using a 21-item telephone questionnaire to evaluate the impact of its activities during 'normal' times, and how they changed to address the challenge of COVID-19."

The arrival of COVID-19 led to a temporary stop in visits following recommendations by the World Health Organization but efforts to provide material and immaterial support and remote monitoring by phone calls were encouraged through a campaign.

Professor Kevern added: "The striking thing about PPI was how quickly and flexibly the movement responded to the pandemic. Innumerable initiatives were undertaken by volunteers such as making masks, collecting food and other donations in order to make the lives of the elderly people monitored by the PPI better throughout Brazil. This was especially important for those who live in places far from urban centres, or in peripheries of large cities where access to social and health services is limited."

"I think we have some lessons to learn from PPI. In the UK, our social care system is also very fragile, and the experience of the early days of the lockdown, where older people were sent into care homes from hospital untested and many died from Covid-19, shows that the present system can't cope. Voluntary movements like PPI, supported and trained by the government, may be indispensable at times of population-level stress like a pandemic. There are some challenges coming down the line - possible future pandemics, Brexit, climate change - when again we might need to adjust to an unstable and rapidly-changing situation. Organisations like PPI might be part of the answer."

A new study led by scientists at IUPUI and Indiana University Bloomington is the first to describe a biochemical mechanism that increases the activity of a molecule whose presence is observed in many types of cancer.

The molecule, an enzyme called Pif1helicase, plays a role in many important cellular processes in the body. Tightly regulating this protein is vital to genome stability because too little -- or too much -- activity can influence aging and age-related diseases, primarily cancer. A common cancer therapy, HDAC inhibitors, can also impact the mechanism that regulates this enzyme.

"We're currently giving people drugs that change the acetylation status of the cell without knowing how it affects many proteins that play a role in genome stability," said Lata Balakrishnan, an associate professor of biology in the School of Science at IUPUI, who is co-lead author on the study.

"HDAC inhibitors upregulate certain tumor-suppression genes, and therefore are used in combination therapies to treat specific cancers, but when it comes to their impact on other parts of the cell, we're basically operating in the dark."

The study's other lead author is Matthew Bochman, an associate professor in the IU Bloomington College of Arts and Sciences' Department of Molecular and Cellular Biochemistry. Other co-authors are Christopher Sausen and Onyekachi E. Ononye, Ph.D. students in Bochman's and Balakrishnan's labs, respectively, at the time of the study.

The effect of lysine acetylation on Pif1 is the mechanism described in the study. Lysine acetylation occurs when a small molecule called an acetyl group binds to lysine, an amino acid used to build common proteins in the body. This action transforms lysine from a positively charged molecule to a neutrally charged molecule. This neutralization can impact protein function, protein stability and protein-protein interaction in cells, among other things.

Helicases are known as the genetic "zippers" of cells because they pull apart DNA for the purpose of genetic replication and repair. They also help maintain telomeres, the structure at the end of chromosomes that shorten as people age.

In the new study, the researchers identified lysine acetylation on Pif1 helicase and showed the addition of the acetyl group increases the protein's activity -- as well as its "unzipping" function. They also found that lysine acetylation changes the shape -- or "conformation" -- of the Pif1 protein. They believe that this shape change increases the amount of Pif1 helicase.

"The dynamic interplay of the addition and removal of the acetyl group on lysine regulates a wide variety of proteins within the cell," Balakrishnan said. "Perturbations to this process can play a role in cancer, aging, inflammatory responses and even addiction-related behaviors."

"As a class, helicases are involved in a lot of processes necessary for genome integrity," Bochman added. "Any significant failure in these processes is generally carcinogenic."

The precise details of lysine acetylation in Pif1, its effect of the enzyme's shape and the resulting impact on helicase activity took nearly five years to observe and report. The study, carried out in parallel on two IU campuses, was made possible by the lead scientists' complementary expertise. As a biochemist who has previously studied lysine acetylation in other proteins, Balakrishnan was able to isolate Pif1 in vitro to observe its response to chemical reactions in a test tube. In contrast, as a geneticist working in yeast as a model organism to study Pif1, Bochman was able to modify cells in vivo to watch reactions play out in a living organism.

"The ability to observe these reactions in a living cell is often more relevant, but it's also a lot messier," Balakrishnan said. "Our experiments were constantly informing each other as to where to go next."

Looking to the future, Bochman said intricate knowledge of cellular processes -- such as lysine acetylation -- will increasingly play a role in personalized therapy.

"If you sequence a patient's tumor, you can fine-tune drugs to target very specific enzymes," he said. "Instead of a drug that broadly affects the whole cell, it will be possible to take a targeted approach that reduces potential side effects. This level of personalization is really the future of cancer biology and cancer medicine."

The newly published thesis research of University of Guam Master of Environmental Science graduate Benjamin Deloso now adds to the body of knowledge about asexual propagation of the most endangered plant group in the world, cycads. His work was part of a set of UOG studies, all focused on improving the asexual propagation of cycads, published in the September 2020 issue of HortScience, one of the oldest horticultural journals in the United States.

With the assistance of his professors, Deloso designed a set of experiments to examine the speed of adventitious rooting in "pups," external stems produced from parent plants. He used two species of Zamia, a group of cycads native to the New World. These model species were chosen for two replicated rooting studies utilizing indole-3-butyric acid (IBA), the most common rooting hormone used in asexual propagation protocols.

Cycad horticulturists typically employ the use of IBA in asexual propagation, and previous research utilizing IBA on angiosperms, or flowering plants, suggests that an ideal concentration of IBA exists for cycads. However, the efficacy of IBA on cycads was unknown. "Do cycads actually benefit from IBA?" wondered Deloso, lead author of the study.

"That was one of our objectives," he said. "So we included a range of IBA that was 10 times higher than the dose that is most commonly used in commercial horticultural operations to see if there would be a negative response."

In contrast to all expectations, the cycad stem cuttings did not appear to benefit from any of the IBA doses used as the control groups performed just as well as the other treatment groups.

"The results were surprising. Our research illuminates how much is still unknown about cycad biology and highlights how different they are from other groups of plants," Deloso said.

This knowledge could benefit cycad conservation in countries where commercial IBA products are difficult to obtain.

Previous asexual propagation studies utilizing cycad stem cuttings did not involve the use of a range of IBA nor did they include a control group.

"After reviewing the scientific literature, it was clear that previous studies did not employ typical horticultural protocols," said Frank Camacho, UOG associate professor of biology and one of the authors of the study.

This makes Deloso's study the first of its kind in the cycad horticulture literature.

While IBA may not influence successful propagation of Zamia cycads, Deloso's study notes that additional studies are needed to determine its effectiveness on the other 300- plus cycad species, in particular those that are threatened, such as the endemic Cycas micronesica of Guam, Rota, Yap, and Palau. He also noted other factors found in his previous research that have proven to assist the propagation process.

"Our previous research has highlighted the relative ease of asexually propagating cycad plants. High survivability is achieved when hygienic conditions are adhered to, cuttings are obtained from healthy plants, the cut surfaces are covered with a sealant to prevent desiccation, the growing medium exhibits adequate aeration and drainage capacity, and underwatering during the propagation phase is followed," Deloso said.

Anders Lindström of the Nong Nooch Tropical Botanical Garden, another author of the study, said he is encouraged by the results of the study, saying, "Continued improvements in cycad horticulture are of great importance to the conservation of this unique plant group. We ... look forward to collaborating more with the University of Guam in the future."

We employ our cognitive skills daily to assimilate and process information. A new empirical study shows that we do better at this task than those born a century ago. But cognitive capacity still begins to stagnate at around the age of 35.

Every day our brains are continuously called upon to meet high-level cognitive challenges. When we write, play games or watch films on our computers, drive a car or carry on a telephone conversation, neurons are constantly transmitting and evaluating the electrical impulses that enable us to filter the incoming sensory information, process it, and decide on and execute the appropriate response. It is now accepted that the ability to perform cognitively demanding tasks and adapt to rapidly changing demands is becoming increasingly important - especially in the workplace.

Perhaps surprisingly, relatively little is known about how an individual's cognitive performance changes over the course of a lifetime. Most research on this topic has been done by psychologists, who have mainly been interested in probing concepts such as the relative contributions of innate and acquired intelligence. But the test procedures employed in this work suffer from two serious shortcomings. First, the tests themselves are usually based on abstract tasks, which have little to do with everyday situations and are therefore unfamiliar to those being tested. Secondly, such experiments provide only a snapshot of each subject's performance level, and therefore have little to say about how a person's cognitive performance changes with age.

Chess as a data source

The authors of the new study - Anthony Strittmatter (University of St. Gallen), Uwe Sunde (Ludwig-Maximilians-Universitaet (LMU) in Munich) and Dainis Zegners (Rotterdam School of Management) - have chosen a very different approach to assess the long-term pattern of change in cognitive capacity with age. "In our empirical model, we have used data derived from chess games played in professional tournaments, since chess is a paradigmatic example of a cognitively complex task," Sunde explains. In fact, the choice of chess as a data source has a number of significant advantages. Detailed data are available that record all the moves made by current and former world champions (and their opponents) over the past 125 years. This makes it possible to gauge the cognitive skills of each player by comparing his actual moves with those suggested by a modern chess computer, which can calculate the optimal move in each configuration that arises during a game. With the aid of mathematical analyses, the resulting data can be converted into a continuous record of each player's level of performance over the course of his entire career. Moreover, because the data cover a period of 125 years, one can also ask whether and how the cognitive abilities of professional chess-players have changed over the course of more than a century.

The empirical model employed by Sunde and his colleagues draws on data for over 24,000 chess games played in professional tournaments between the years 1890 and 2014, which record more than 1.6 million individual moves. When these data are analyzed for 'age cohorts' - groups defined by the birthdates of the players - the following conclusions can be drawn:

Cognitive performance follows an age-dependent trajectory. It increases steadily at first, before reaching a plateau at around the middle of the fourth decade.

The form of this profile has changed over the past 125 years. On average, those born later during this time-span exhibit a higher level of cognitive ability than their predecessors at the same age, as indicated by the relative increase in the choice of optimal moves during a game.

However, as Sunde explains, one must take one feature of the data into account when interpreting these results. "The problem arises from the fact that professional chess-players stop participating in tournaments at some stage, because they are no longer good enough to be competitive. This factor opens up the possibility that what are called 'selection effects' might distort the quantitative analysis of the data, which would reduce confidence in the interpretation of the model. This effect is expected to set in from the age of 50 or so. "If players continued to play regularly in public tournaments throughout their lives, the impact of the selection effect would be lower, and the trajectory of the curve for overall cognitive performance would probably fall off at a somewhat faster rate." For this reason, Sunde explains, the performance curve may not apply to the general population, but rather represents an upper bound.

Professor Sunde and his co-authors also provide a possible rationale for their finding the mean cognitive capacity of today's 30-year-olds is higher than that of the corresponding age group 100 years ago. "Our results suggest that the conditions under which people grow up these days - which of course include the rapid growth of digital technology -­ have a decisive impact on the development of their cognitive abilities," he says. However, he adds, the model has nothing to say about whether this trend is likely to continue.

At all events, those of us who have already passed the 35-year threshold need no longer worry about its looming approach. - And if one continues to exercise one's gray matter regularly, there's a good chance that the brain will return the favor by remaining sprightly for longer.

TAMPA, Fla. -- Prostate cancer is the most common type of cancer among American men after skin cancer, but the disease does not affect all races equally. African American men are nearly two times more likely to develop prostate cancer, and more often have an aggressive form of the disease that grows and spreads quickly. They are also two times more likely to die from prostate cancer compared to white men. While the health care community is aware of this disparity, little is known about why prostate cancer affects African American men differently. It has become increasingly evident that both socio-economic and biological factors may contribute to the disparity.

Moffitt Cancer Center researchers are taking a closer look at the genomic features of prostate cancer tumors among men of different races in hopes of better understanding why African Americans are more susceptible to the disease. In a new article published in Clinical Cancer Research, the research team describes the immune-oncologic differences in prostate cancer tumors of African American men and how those variations may be exploited to develop more personalized treatment approaches for this population.

"Previous studies have looked at the immune landscape of prostate cancer in white or European American men but have lacked validation among their African American counterparts," said Kosj Yamoah, M.D., Ph.D., lead study author and assistant member of the Radiation Oncology and Cancer Epidemiology Programs at Moffitt. "Our genomic analysis, the largest of its kind, revealed there are major immune pathways that are significantly elevated in African American men, which can correlate with risk of cancer recurrence and poor outcomes."

The Moffitt researchers analyzed whole transcriptome data from nearly 1,200 proctectomy samples in the Decipher Genomic Resource Information Database registry. Transcriptomic data provides a complete look at all the RNA sequences within a cell, which in turn can show when and where each gene is turned on or off. The team focused on 1,260 immune specific genes to determine differences between prostate cancer tumor cells in African American and European American men.

They discovered striking differences between the two races. Major immune pathways, including cytokine, interferon and interleukin signaling, are elevated in African American prostate tumors. These pathways can contribute to and escalate the growth and spread of cancer cells. The immune biologic signatures suggest prostate cancer tumors in African American men may be more sensitive to radiotherapy and could have a better response to immunotherapy.

"Currently there are only two immunotherapy options for prostate cancer patients: the sipuleucel-T cell vaccine and pembrolizumab. However, not everyone responds to those therapies," said Yamoah. "Our study shows that African American men have higher overall immune content within their tumor microenvironment and higher expression of T lymphocytes. We can use that information to select a therapy that better targets their tumor and therefore improve their outcome."

The team also discovered six genes that expression levels were consistently different between African American and European American men. One gene, IFITM3, is often an indicator that a patient has a significantly higher risk of biochemical recurrence, meaning their prostate antigen score continues to rise despite surgery or radiation. In addition to cancer progression, this gene also plays an important role in metastasis.

The researchers say further study will be needed to determine if their findings can have positive implications on the treatment and management of prostate cancer in African American men.