Publisher Health

A new antibiotic compound clears infection of multi-drug resistant gonorrhea in mice in a single oral dose, according to a new study led by researchers at Penn State and Emory University. The compound targets a molecular pathway found in bacteria but not humans and could lead to new treatments for gonorrhea and infections from other bacteria, such as tuberculosis and MRSA.
The research team, which also includes scientists from the biopharmaceutical company Microbiotix, the Uniformed Services University, and Florida State, published their results in a paper appearing March 19 in the journal Nature Communications.
Gonorrhea infects more than 500 thousand people in the United States each year, and several strains of the bacteria that causes the disease, Neisseria gonorrhoeae, are resistant to multiple antibiotics in use today. For this reason, the Centers for Disease Control and Prevention (CDC) lists multi-drug resistant gonorrhea as one of the five most dangerous urgent threats today.
“Many current antibiotics target the process of translation — when proteins are made based on information in genetic material — within the bacteria,” said Ken Keiler, professor of biochemistry and molecular biology at Penn State and an author of the paper. “Over the last decade, we have been investigating a family of compounds that instead inhibit the trans-translation pathway in bacteria, which bacteria use to fix certain kinds of errors during protein synthesis. In this paper, we provide a proof-of-concept that inhibiting the trans-translation pathway can effectively clear multi-drug resistant gonorrhea in animals.”
The researchers previously identified a promising trans-translation inhibitor that clears gonorrhea infection in lab cultures but is ineffective in animals because the compound breaks down. In this study, members of the research team at Microbiotix strategically altered the compound to identify which portions of its structure were necessary to inhibit the pathway and which could be changed to improve its stability.
“Our iterative optimization campaign evaluated over 500 versions of the compound to assess their potency, toxicity, and other pharmacological properties,” said Zachary Aron, director of chemistry at Microbiotix and an author of the paper. “We determined that the central region of the compound plays a critical role in blocking the trans-translation pathway, however modifications at the periphery could be altered to modulate its pharmacological properties. By altering a functional group to sidestep the primary mechanism of metabolism, we can create versions of the compound that are much more stable in animals.”
Members of the research team at the Uniformed Services University then tested one of these modified compounds, MBX-4132, in mice. Their experiments utilized the gonorrhea strain WHO-X, an extremely virulent pathogen that is resistant to almost all approved antibiotics. A single oral dose of the compound completely cleared the infection in 80% of mice within six days, and the bacterial load in the remaining 20% was dramatically reduced.

A growing number of studies show that the environmental factors and lifestyle habits of pregnant women play an important role in the health of their child. But how about the semen quality of young men? Researchers at the University of Geneva (UNIGE), Switzerland, showed two years ago that only 38% of Swiss men had semne parameters above the thresholds set by the World Health Organisation (WHO) for fertile men. Epidemiologists from the Institut de recherche en santé, environnement et travail (IRSET, Rennes, France), in collaboration with the UNIGE team analyzed the potential impact of endocrine disruptors on semen quality of men whose mothers were working at the early stages of their pregnancy. Their results, published in the journal Human Reproduction, show that men who have been exposed in utero to products known to contain endocrine disruptors are twice more likely to have semen volume and total sperm count per ejaculation below the reference values set by the WHO.
Endocrine disrupters are chemical substances of natural or synthetic origin which can interfere with the endocrine system and causes adverse health effects in an organism, or its progeny, according to the World Health Organization (WHO). “Several animal studies have already shown that gestational exposure to certain endocrine disruptors can influence the development of the male reproductive system, as well as the sperm production and semen quality in adulthood,” explains Ronan Garlantézec, a researcher at the IRSET, the Rennes University Hospital Centre (CHU) and University of Rennes 1. “In view of the results obtained by Serge Nef’s team on the semen quality of young Swiss men, we were interested in studying the potential effect of exposure to endocrine disruptors during pregnancy as one out of many possible reasons behind the observed trends,” he continues.
The semen of more than 1000 conscripts analysed
The team of Serge Nef, professor at the Department of Genetic Medicine and Development of the UNIGE Faculty of Medicine, has evaluated semen quality of around 3000 conscripts, 1045 out of which had their mother working during pregnancy. “For each of them, a semen quality analysis was carried out to determine the semen volume, as well as the sperm concentration, motility and morphology,” explains the Serge Nef. “A detailed questionnaire was also sent to the parents before the semen analysis was carried out, covering in particular the maternal jobs exerted during the conscripts’ pregnancy period.”
This allowed for the analysis of semen parameters of men whose mothers were employed during their pregnancy. “The maternal jobs were classified according to the International Classification of Occupations (ISCO-88 of the International Labour Office of the WHO),” explains Luc Multigner, research director at the IRSET. “Exposure to products containing endocrine disruptors during pregnancy has been defined using a job-exposure matrix, which makes it possible to attribute the maternal exposure a probability score.” This has enabled epidemiologists to establish probabilities of exposure to one or more categories of products that may contain endocrine disruptors according to the mother’s occupation.
Endocrine disruptors associated with poorer sperm quality
The results of this study show that young men exposed in utero to endocrine disruptors are twice as likely to have values below the reference values established by the WHO, both in terms of the semen volume (threshold at 2 ml) and the total number of spermatozoa per ejaculation (40 million). “In our study, the products most associated with these anomalies were pesticides, phthalates and heavy metals,” notes Ronan Garlantézec.
“These observations do not determine the future fertility of young men, and only a follow-up over time will make it possible to assess the consequences. Nevertheless, the results could explain, at least in part, the low semen quality of some young Swiss men,” Serge Nef continues. An additional study is already planned in this same population to study the link between maternal occupational exposure to endocrine disruptors and changes in sexual hormones during adulthood.
Preventing exposure to endocrine disruptors
The results of this study suggest an association between the mother’s occupational exposure to endocrine disruptors and a decrease in several semen parameters in their children during adulthood. “It therefore appears necessary to inform women planning to conceive and during their early stages of pregnancy of the potential hazards of exposure to these substances, which could alter their children’s fertility,” underlines Luc Multigner. “Similarly, it would be interesting to carry out a similar study in women, in order to evaluate whether the impact of endocrine disruptors is the same on the female reproductive system, although this is much more complex to carry out,” explains Ronan Garlantézec. Finally, the data concerns mothers 25 years ago. Since then, the professions exerted by women have greatly evolved, as has the presence of endocrine disruptors in the products used. “Hence the crucial preventive role of this study,” concludes Serge Nef.
Story Source:
Materials provided by Université de Genève. Note: Content may be edited for style and length.

For the first time researchers from Hebrew University of Jerusalem, Radboudumc, Maastricht UMC+ and international colleagues have gained insight into the “hidden genetic defects” of the general European population. This is important because these defects, if inherited from both father and mother, can lead to all kinds of illnesses in their children. Research in the Dutch and Estonian population shows that every person has two to four such hidden genetic defects. In 1 in 100 couples, this leads to a situation with an increased risk of a genetic disease for future children. In the case of consanguinity, even 20 percent of the couples appear to be at high risk. This research is published in The American Journal of Human Genetics and Genetics in Medicine.
The genes of a every person are half maternal, half paternal. Therefor you have two copies of each gene. Sometimes one of those two copies is defective, without making you sick because the other gene still functions properly. In this case we call it a ‘hidden genetic defect’ (in scientific terms: an autosomal recessive gene). Such a hidden genetic defect can cause problems if a child inherits the same hidden defect, the same mutated gene, from both father and mother. Both parents are healthy and have never suffered from the hidden genetic defect. But when these two hidden genetic defects (maternal en paternal) come together in the child, the disease manifests itself.
Hidden defects in sight
How often such hidden genetic defects occur in the general population has been unclear. By screening all the genes of nearly 6,500 people in the Dutch and Estonian population researchers from Radboudumc and Maastricht UMC+ have now obtained insight into how often such hidden defects that can lead to disease are present in a single individual. Christian Gilissen, researcher at Radboudumc: “Every human being appears to have on average 2 to 4 such hidden genetic defects. Therefore the chance that a European couple is at risk of having a sick child due to two such defects is about 1 percent. The risk increases sharply in consanguineous couples. In a relationship of cousins, about sixteen percent of the couples are at high risk, with a particularly increased risks for skeletal disorders or intellectual disabilities.”
Higher risk with consanguinity
In addition to this research, published in The American Journal of Human Genetics, research was also conducted in the hospital’s clinical practice coordinated by Maastricht UMC+, together with Radboudumc and Amsterdam UMC. This study, published in Genetics in Medicine, addresses the question of risk determination of hidden genetic defects in cousin relationships prior to a desired pregnancy. Clinical Molecular Geneticist Aimee Paulussen of Maastricht UMC+: “We mapped the risk in 100 consanguineous couples. About 20 percent of these couples were found to have an increased risk of serious disorders in their offspring through these hidden genetic defects. These results from clinical practice confirm the data already found in the population study mentioned above.”
Valuable testing
Professor Han Brunner, head of the Department of Clinical Genetics Maastricht as well as the Department of Genetics Nijmegen, is involved in both studies. He sees them as a clear incentive to make genetic testing available to couples with a possible increased risk because of such hidden genetic defects: “Certainly for these couples, this information can help them to make an informed decision when starting a family. They can consider pre-implantation diagnostics and IVF to allow selection of embryos without these defects.”
Story Source:
Materials provided by Radboud University Medical Center. Note: Content may be edited for style and length.

Flashlight fish have the ability to generate situation-specific blink patterns resembling a visual Morse code. Researchers at Ruhr-Universität Bochum have shown in laboratory and field experiments that the animals use these light signals to coordinate their behaviour in the school when visibility is limited. Both the light intensity and the blinking frequency affected the animals’ behaviour. The team headed by Peter Jägers and Professor Stefan Herlitze from the Department of General Zoology and Neurobiology has shared their findings in the journal Scientific Reports, published online on 19 March 2021. “Our data show that flashlight fish are attracted by the light signals emitted by other school members,” points out Jägers.
Milky Way in the water
Flashlight fish of the species Anomalops katoptron have a luminescent organ under their eyes that is filled with luminescent bacteria and which they can occlude so that it looks as if they are blinking. During the day, the animals hide in caves, rock crevices or in dark, deep water. “On moonless nights, up to a thousand individuals migrate in a school into the plankton-rich surface water,” says Peter Jägers, who observed the fish in the wild during a diving expedition in the Indo-Pacific. “It is a surreal experience to see the schools — like a Milky Way in the water.”
To understand the function of the flashing patterns, the researchers first studied Anomalops katoptron in the lab in a large water tank containing fish dummies that could be digitally controlled to mimic the animals’ light signals. They also used infrared cameras to record the movements of individual animals in response to the artificial flashing lights. During the experiments, only one animal was in the tank at a time, with several individuals being tested one after the other.
Flashlight dummies attract fish
When the researchers placed a single dummy that was flashing light in the middle of the tank, the fish moved closer to it the faster the light flashed. In another experiment, 13 lights were positioned around the tank and lit up one after the other at varying time intervals. “We observed a high motivation among the flashlight fish to head towards the light,” says Peter Jägers.
Based on the laboratory experiments, the researchers deduced that a faster flashing is a signal for Anomalops katoptron to stay closer to their fellow fish in the school, as the group offers, for example, protection from predators. This theory was confirmed in field experiments. On a diving expedition, the researchers showed that the animals reacted to stress by blinking more rapidly.
Waiting for the school at night in the sea
Diving at night in the dark, the researchers waited until a school of flashlight fish got close. The animals avoided light brighter than moonlight by fleeing immediately. The Bochum team triggered the escape response with dim red light and simultaneously recorded the animals and their blinking patterns with special cameras. This is how they showed that stress was associated with an increased blinking frequency. “We assume that the increased blinking frequency is the signal to follow the other group members more closely under stress,” concludes Peter Jägers. “In our study, we demonstrated for the first time that there is a direct link between visually communicated signals under limited light conditions, such as those prevailing at night or in the deep sea, and the school formation of fish. We hope that this can be of help in future studies of, for example, the largely unexplored deep sea.”
Story Source:
Materials provided by Ruhr-University Bochum. Note: Content may be edited for style and length.

Recent generations show a worrying decline in health compared to their parents and grandparents when they were the same age, a new national study reveals.
Researchers found that, compared to previous generations, members of Generation X and Generation Y showed poorer physical health, higher levels of unhealthy behaviors such as alcohol use and smoking, and more depression and anxiety.
The results suggest the likelihood of higher levels of diseases and more deaths in younger generations than we have seen in the past, said Hui Zheng, lead author of the study and professor of sociology at The Ohio State University.
“The worsening health profiles we found in Gen X and Gen Y is alarming,” Zheng said.
“If we don’t find a way to slow this trend, we are potentially going to see an expansion of morbidity and mortality rates in the United States as these generations get older.”
Zheng conducted the study with Paola Echave, a graduate student in sociology at Ohio State. The results were published yesterday (March 18, 2021) in the American Journal of Epidemiology.

In a paper published in the Journal of General Internal Medicine, physician-researchers at Beth Israel Deaconess Medical Center (BIDMC) assessed the relative impact of COVID-19 on patients hospitalized with the viral infection in March and April 2020, versus patients hospitalized with influenza during the last five flu seasons at the medical center. Overall, the team demonstrated that COVID-19 cases resulted in significantly more weekly hospitalizations, more use of mechanical ventilation and higher mortality rates than influenza.
COVID-19 and influenza are both contagious respiratory viral diseases that can lead to pneumonia and acute respiratory failure in severe cases. However, detailed comparison of the epidemiology and clinical characteristics of COVID-19 and those of influenza are lacking.
“COVID-19 has been compared to influenza both by health care professionals and the lay public, but there’s really limited detailed objective data available for comparing and contrasting the impact of these two diseases on patients and hospitals,” said corresponding author Michael Donnino, MD, Critical Care and Emergency Medicine physician at BIDMC. “We compared patients admitted to BIDMC with COVID-19 in spring 2020 to patients admitted to BIDMC with influenza during the last five flu seasons. We found that COVID-19 causes more severe disease and is more lethal than influenza.”
Donnino and colleagues included a total of 1,634 hospitalized patients in their study, 582 of whom had laboratory-confirmed COVID-19 and 1,052 of whom had confirmed influenza. The team found that, on average, 210 patients were admitted to BIDMC during each eight-month flu season, compared to the 582 patients with COVID-19 admitted in March and April 2020. While 174 patients with COVID-19 (or 30 percent) received mechanical ventilation during the two-month period, just 84 patients with influenza (or 8 percent) were placed on ventilation over all five seasons of influenza. Likewise, the proportion of patients who died was much higher for COVID-19 than for influenza; 20 percent of admitted patients with COVID-19 died in the two-month period, compared to three percent of patients with influenza over five seasons.
Further analysis revealed that hospitalized patients with COVID-19 tended to be younger than those hospitalized with influenza. Among patients requiring mechanical ventilation, patients with COVID-19 were on ventilation much longer — a median duration of two weeks — compared to just over three days for patients with influenza. Moreover, among patients requiring mechanical ventilation, patients with COVID-19 were far less likely to have had pre-existing medical conditions.
“Our data illustrate that 98 percent of deaths of patients hospitalized with COVID-19 were directly or indirectly related to their COVID-19 illness, illustrating that patients did not die with COVID but rather from COVID pneumonia or a complication,” said Donnino.
The authors note that the stringent social distancing guidance in effect last spring may have impacted these findings by limiting the incidence and lethality of COVID-19 toward the end of April 2020. Conversely, some treatment practices have evolved over the course of the pandemic, potentially improving outcomes for patients with COVID-19.
Co-authors included Ari Moskowitz, MD, Garrett S. Thompson, MPH, Stanley J. Heydrick, PhD, Rahul D. Pawar, MD, Katherine M. Berg, MD, Shivani Mehta, Parth V. Patel, BSN, RN, and Anne V. Grossestreuer, PhD, all of Beth Israel Deaconess Medical Center.
This work was supported by internal funding. Donnino, Moskowitz and Berg are supported in part by grants from the National Institutes of Health (K24HL127101, R01HL136705 and 1R01DK112886; K23GM128005; and K23HL128881404).

Three University of Colorado Cancer Center researchers are part of a team that recently published a paper offering new insight into how the immune system relates to cancer. Quentin Vicens, PhD, Jeffrey Kieft, PhD, and Beat Vögeli, PhD, are authors on the paper, which looks at how an enzyme called ADAR1 operates in pathways associated with cancer.
“In a cell, ADAR1 edits native RNA — or self-RNA — so that the cell recognizes it as its own. It’s a key protection against autoimmune disorders,” Kieft says. “But if a virus infects, viral RNA isn’t edited by ADAR1, so the cell can recognize that and react. The cell knows it has foreign RNA, and it activates immune responses to fight off that infection.”
For their paper published last month in the journal Nature Communications, Kieft, Vögeli, Vicens, and the rest of the team — including Parker Nichols, a graduate student in the Structural Biology and Biochemistry program in the CU School of Medicine who works jointly in the Kieft and Vögeli labs — looked at where specifically the ADAR1 binds to RNA to perform the editing process. They already knew a domain of ADAR1 known as Z-alpha binds to a form of RNA called Z-RNA, but they found that Z-alpha ADAR1 can bind to other RNA forms as well.
“The team asked, ‘How are all these locations in RNA being recognized by Z-alpha if they supposedly don’t form Z-RNA?'” Kieft says. “One of the take-home messages is that other forms of RNA can bind to Z-alpha ADAR1 and can even partially form Z-RNA. That was a surprise because it shows that RNA can form this specific Z structure in places we didn’t recognize before.”
The team is now proposing a model for how Z-alpha ADAR1 is able to bind to different types of RNA. It’s an important finding in cancer research because of the role of ADAR1 in cancer regulation. A normally functioning immune system oftentimes can detect cancerous cells as being dangerous and then eliminate them, but if there’s too much ADAR1 editing happening, a cell could be tamping down the immune response in an effort to protect itself.
“In a lot of cancers, there is upregulation of ADAR1; it is doing more than it should,” Kieft says. “The excess ADAR1 presumably is leading to more RNA editing than is normal. This is going to misregulate things,affecting specific regions of RNA or types of RNA. The excess editing is going to throw off the normal immune response, but it probably has a lot of other affects in the cell as well. Cancer is a disease where gene regulation has gone awry, so if an important regulatory pathway like editing by ADAR has gone haywire, that can contribute to the cancer.”
Knowing all the targets of ADAR1 in a cell is also a step toward more effective therapies, Kieft says. If researchers understand the pathways, they may be able to find a way to disrupt the overactive editing process and boost the immune response. It’s a finding applicable to many other diseases as well — Vögeli says since the paper was published, the researchers have heard from other scientists around the country interested in ADAR1.
“We have gotten a lot of feedback on the paper,” he says. “There is a lot of interest in this field right now, and other people are interested in how they could use our structural information.”
Vögeli and Vicens are now organizing a meeting focused on ADAR1 function and putting together special issues of the journals Molecules and International Journal of Molecular Sciences.
Vicens says the research project also illustrates the importance of collaborative work and being open to new directions. “I basically brought a new project and direction to the Kieft lab when I joined,” Vicens says. “Both labs were open to supporting it intellectually and financially, and the resultant team effort enabled research that would not otherwise have been done.”

Easter, Passover and Ramadan will be a little less lonely this year as more people get vaccinated. But experts say we can’t let down our guard just yet.The weather is warming, the days are looking brighter and the number of people getting vaccinated is on the rise. So can we finally celebrate the spring holidays together like we used to, back when we could see the bottom halves of everyone’s faces?Well, not exactly.Although coronavirus cases and deaths are declining nationwide and the Centers for Disease Control and Prevention recently issued new, looser safety guidelines for vaccinated people, the agency recommended against unmasked indoor gatherings with unvaccinated people except in certain circumstances.We asked public health experts to help us understand the latest guidance and offer advice on how to safely observe upcoming holidays like Easter, Passover and Ramadan.Do we need to wear masks and stay six feet apart?According to the C.D.C., if the people in your home have been fully vaccinated, meaning at least two weeks have passed since each person’s final shot, you can spend time together unmasked with the unvaccinated members of one other household — either indoors or outdoors — without physical distancing. But this holds true only if all of the unvaccinated people are not at increased risk of severe illness if they were to contract Covid-19, the agency said.The risk of transmission between a vaccinated household and an unvaccinated household “is incredibly low,” said Dr. Joshua Barocas, an infectious diseases physician at Boston Medical Center.And when both households are vaccinated, the risk is even lower, he added.Erica Fleischer, 42, a public policy expert and mother of two who lives in Chicago, said her family would typically celebrate Passover Seder, held on the first two nights of the eight-day holiday, at her in-laws’ home, surrounded by as many as 20 people.Last year they met virtually, but this year, given the new C.D.C. guidance, her unvaccinated family will have a small dinner with her in-laws, who have each received the vaccine.Ms. Fleischer said she feels “pretty confident” the risks of infecting one another are low. “I think I actually needed more convincing than my in-laws did.”Dr. Shaun Din, 35, a radiation oncologist in Manhattan, is planning to spend part of the holy month of Ramadan with nearby family members. Five of the eight adults, including Dr. Din and his parents, have been vaccinated, so the family feels comfortable meeting unmasked on weekends for the evening iftars that break each daylong fast.“Last year was very lonely, not being able to celebrate together,” Dr. Din said. “Ramadan is difficult, but the communal aspect of all of us going through it and then breaking the fast together is something that’s very fun.”Can we invite more than one household?If you are fully vaccinated and you would like to invite other fully vaccinated friends over for dinner, the C.D.C. says that “it is likely a low risk,” and there is no need to wear masks or stay physically distanced.Even so, keep the get-together small. The C.D.C. advises against medium- or large-size gatherings (though it hasn’t defined what constitutes medium or large).“Variants are circulating, and the vaccines might not be quite as effective against them,” said Linsey Marr, a professor of civil and environmental engineering at Virginia Tech who studies viruses in the air.If you plan to mix unvaccinated people from multiple households, experts suggest holding the gathering outside, staying six feet apart and wearing masks.And if you decide to spend time indoors with unvaccinated people from other households, wear a mask and open the windows to improve the ventilation, said Shelly Miller, a mechanical engineering professor at the University of Colorado, Boulder, who studies airborne disease transmission in enclosed spaces. She also suggested using a HEPA filter air cleaner certified by the Association of Home Appliance Manufacturers.What about unvaccinated kids?The coronavirus vaccine is not currently available to most children because clinical trial results are still forthcoming.Say there are two healthy families of four. If the kids aren’t vaccinated in either household but all of the adults are, you might consider inviting people inside as long as the windows are open and everyone is wearing masks, said Dr. Asaf Bitton, a primary care physician who runs a public health research laboratory at Brigham and Women’s Hospital in Boston. If the kids in neither household are vaccinated and only one set of adults has been vaccinated, he and other experts said an outdoor gathering with masks and distancing would be safest.You may also be wondering if your unvaccinated children can finally get a hug and kiss from their healthy, vaccinated grandma. On this question, the experts’ opinions diverged. But in general, if everyone is healthy and you’re comfortable accepting some degree of risk, a hug or kiss is probably fine.“The likelihood that my kid transmits a virus that ends up causing severe disease in my vaccinated parents is very, very low,” Dr. Barocas said.Similarly, he added, it’s unlikely that a vaccinated adult would transmit the virus to a child. That said, the experts advised doing what feels right to you and your family.“I think everyone going into that visit needs to understand that we’re balancing risks and benefits,” said Dr. Adam Ratner, director of the division of pediatric infectious diseases at Hassenfeld Children’s Hospital at N.Y.U. Langone. But, he added, if the grandparents are vaccinated, “I am pro hugging and kissing.”Jennifer Rogers, 46, an attorney in Philadelphia, said her husband and two children, 8 and 11, will celebrate Easter by visiting her parents’ home for several hours. They’re planning on having an outdoor Easter egg hunt and whacking away at a coronavirus-shaped piñata. But the kids, who will be joined by Ms. Rogers’s sister and her sister’s son, will all be wearing masks. Ms. Rogers and her husband are both vaccinated, but they are planning to wear masks too, because their family will have recently returned from a Florida vacation.“It still feels like a loss, like it’s not the same as it’s been,” said Ms. Rogers, whose family typically stays overnight at her parents’ home during the holiday.Can our fully vaccinated relatives fly out to see us?The C.D.C. is still saying no.“We know that after mass travel, after vacations, after holidays, we tend to see a surge in cases,” the C.D.C. director, Dr. Rochelle Walensky, said last week on MSNBC. “And so, we really want to make sure — again with just 10 percent of people vaccinated — that we are limiting travel.”We are also still learning whether vaccinated people without symptoms can unknowingly carry infections to the households that they are visiting, Dr. Bitton said.“Travel in little metal tubes and crowded airports and taxi cabs brings risks of transmission,” he added.Danielle Nuzzo, 36, a communications manager whose family celebrates both Easter and Passover, lives in California with her husband and 2-year-old daughter, across the country from both sets of grandparents. As soon as the grandparents got vaccinated, they asked if they could visit during the holidays, she said. But Ms. Nuzzo and her husband are not vaccinated yet, and they didn’t feel comfortable hosting anyone who had just hopped off a plane. In the end, they decided they will celebrate just like they did last year, over Zoom.“It’s really hard. It’s emotional,” Ms. Nuzzo said. “We want her to know who her grandparents are and see them. But we also want to do what’s right and just be safe.”If your family does decide to travel, the C.D.C. recommends first getting fully vaccinated for the coronavirus, if you are eligible, and also getting a Covid-19 test one to three days before the trip. All travelers, regardless of whether they are vaccinated or not, must wear a mask; try to stay at least six feet from others; get tested again three to five days after your trip and quarantine for seven days, even if your test is negative. (If you don’t get tested, the C.D.C. says you should quarantine for 10 days.)Check your state and local requirements because different areas have different rules. New York State, for example, says domestic travelers do not need to quarantine during the first three months after being fully vaccinated, provided that they are asymptomatic.What if my relatives and I disagree about what’s safe?After a year of public health warnings, some family members might feel uneasy about loosening the rules while others might be anxious to get back to normal.Last year, ahead of the Thanksgiving holiday, Claudia W. Allen, a clinical psychologist and the director of the Family Stress Clinic at the University of Virginia School of Medicine, told The New York Times that if there are differences of opinion, it’s important not to pass judgment, start lecturing or assume that your relatives have bad motives.“The people who are willing to take more risks are usually doing it because they’re valuing connection. And the people who are less willing to take risks are usually less willing because they are prioritizing safety. Connection and safety are both good,” Dr. Allen said at the time.The same advice applies for spring holidays. “A new tricky aspect is that some people are vaccinated and others aren’t,” she added this week.If you’re at odds with a family member, don’t forget to recognize the other person’s good intentions, even if you ultimately have to agree to disagree, Dr. Allen said. Take a moment to also acknowledge their feelings and the uncertainty of the situation and say, “I totally understand your caution; we each have to try to weigh the risks as best we can.”

SharecloseShare pageCopy linkAbout sharingimage copyrightGetty ImagesIndia, one of the world’s largest producers of coronavirus vaccines, is struggling to meet its export commitments.Its largest manufacturer says doses intended for the UK could be held up, and a big order to supply Nepal has also been put on hold.Why the shortfall? The Serum Institute of India (SII) – which produces Novavax and AstraZeneca vaccines – recently raised concerns about raw material shortages.Its chief executive, Adar Poonawalla, attributed this to US export bans on specific items needed to make vaccines, such as specialised bags and filters.image copyrightAFPThe firm said it has also faced difficulties importing cell culture media, single-use tubing and specialised chemicals from the US. “The sharing of these…raw materials is going to become a critical limiting factor — nobody has been able to address this so far,” said Mr Poonawalla.The SII has written to the Indian government asking it to intervene to ensure the uninterrupted manufacture and supply of vaccines globally. Another Indian manufacturer, Biological E, which is producing the Johnson & Johnson vaccine, has also raised concerns about possible shortages affecting vaccine production.Mahima Datla, the company’s chief executive, recently said US suppliers were “reluctant to commit that they will stick to their delivery timelines”.Why is the US restricting supplies?President Biden has asked his administration to identify potential shortfalls in materials required for vaccine production.He has invoked the Defense Production Act (DPA), legislation from the 1950s which gives the US president powers to mobilise the domestic economy in response to emergencies. The DPA allows the US to restrict the export of products which might be needed for domestic manufacturing. The Biden administration said it would use the act to increase the list of items that US vaccine makers would get priority access to, such as special pumps and filtration units.Representatives of various global vaccine makers raised concerns in early March, warning that:Export restrictions from key suppliers could affect global productionSome items lack standardisation and are highly specialisedReplacement with substitutes sourced from elsewhere could take up to 12 monthsDr Sarah Schiffling, an expert on vaccine supply chains at Liverpool’s John Moores University, says the pharmaceutical supply chain is very complex.”Even when demand is very high, new suppliers can’t spring up as quickly as they would in some other industries, or at least those new suppliers would not be trusted.”She also says that the US measures are as much a reaction to existing global shortages, as they are the cause of them.”To some degree, shortages would be unavoidable for materials needed for any kind of product that is suddenly in demand around the world,” she says.Impact on India’s vaccine productionimage copyrightGetty ImagesThere are currently two vaccines approved in India – the Oxford-AstraZeneca vaccine (known locally as Covishield) and Covaxin, developed in Indian laboratories.Since early January, nearly 130 million doses of Covishield from the SII have been either exported or used domestically.Indian pharmaceutical companies have been ramping up production by adding new facilities or converting existing production lines for some months now, both to meet domestic demand and meet global supply requirements.The Serum Institute said in January it could at that point turn out between 60 and 70 million vaccine doses a month – this includes Covishield and the US-developed Novavax (not yet licensed for use).

Getty ImagesTop Indian Covid vaccine makersSIICovishield, NovavaxBharat BiotechCovaxin, CoraVaxBiological EJohnson & JohnsonZydus CadilaZyCoV-DHetero BiopharmaSputnik VDr Reddy’s LabSputnik VSource: Media reportsThe SII told the BBC back then it was aiming to boost production to 100 million doses a month from March – but when we checked with them recently, production was still at 60 to 70 million doses, and had not increased.The company did not clarify if it already had stockpiles of the vaccines it produces, and how much of its production has been earmarked for domestic use only.Is India meeting domestic needs?The Indian government began its vaccination programme on 16 January, and so far the country has inoculated over 39 million people amid fears of a possible second wave. Infections have been increasing in some parts of the country.The authorities aim to administer 600 million doses within seven months – that’s about 85 million doses a month.image copyrightEPASo far, the SII has an agreement to supply 100 million doses to the Indian government, with another firm, Bharat Biotech, supplying 10 million doses.India also has licensing deals with the Russian Gamaleya Research Institute to produce 200 million doses of the Sputnik vaccine.These will be produced by Indian manufacturers, for both the Indian market and for export. The SII chief, Adar Poonawalla, indicated in January that official approval for Covishield was granted on the understanding that company prioritise Indian domestic needs.However, the Indian government subsequently made clear there were no restrictions on exports, after Bangladesh queried if a contract to supply Covishield would be honoured.Who will get India’s vaccines?India’s SII also has commitments to the UN-backed Covax initiative to help low and middle-income countries secure access to vaccines.Last September, the SII agreed to supply 200 million doses to Covax – either the AstraZeneca or Novavax vaccines.image copyrightAFPThe SII has also made bilateral commercial deals, amounting to nearly 900 million doses of AstraZeneca vaccine, and 145 million doses of Novavax, according to UN data.The Indian government has also donated vaccines to a number of countries, with a particular emphasis on its neighbours in South Asia.It’s so far made more vaccine donations than China with over eight million doses given away, compared with 7.3 million, according to UN data. Read more from Reality CheckSend us your questions

.layout-medium .main{max-width:none}@media screen and (max-device-width:767px),screen and (max-width:767px){.main{margin:0;padding:0}}.ad.top-ad{overflow:hidden;width:100%;max-width:100%;margin-left:0;margin-right:0}.lede-container-ads{display:none;position:relative}.bottom-container-ads{text-align:center}.sharetools-story{display:none}.page-interactive-app .story-header{padding:0 16px}.comments-button.theme-kicker{display:none}#sharetools-interactive{top:-6px}.viewport-small-10 #sharetools-interactive{top:0}.story.theme-main .story-header .story-meta .story-heading{line-height:1}.page-interactive .story.theme-main .story-header{border:0;margin:0 auto;padding:0 16px}.page-interactive .story.theme-main .story-header .story-meta{margin-bottom:0}.page-interactive .story.theme-main .story-header .story-meta .kicker-container{margin-bottom:10px}.page-interactive .story.theme-main .story-header .story-meta .kicker-container #sharetools-interactive{left:auto;right:16px;bottom:auto;display:block}.page-interactive .story.theme-main .story-header .story-meta .story-heading{font-family:nyt-cheltenham,georgia,times new roman,times,serif;font-size:42px;line-height:1.1;margin:0 auto;text-align:left}.page-interactive .story.theme-main .story-header .story-meta .story-meta-footer .summary{font-family:nyt-cheltenham,georgia,times new roman,times,serif;font-size:18px;font-weight:100;margin-top:15px;margin-bottom:0;line-height:1.3;color:#666}.page-interactive .story.theme-main .story-header:after{content:””;display:block;background:#e2e2e2;height:1px;width:auto;margin-top:32px}.video_container .nytd-player-container{margin-bottom:7px}.media.photo[data-media-action=modal]{pointer-events:none}.media-viewer-asset img{width:100%;display:block}.leadin-body{border-bottom:1px solid #ccc;padding:0 16px 20px}.marginalia{display:none;border-top:1px dotted #999;width:300px;float:right;clear:right;margin:5px 0 45px 30px;padding-top:10px}.marginalia .module-heading{font-size:11px;font-size:.6875rem;line-height:11px;line-height:.6875rem;font-weight:700;font-family:nyt-franklin,arial,helvetica,sans-serif;color:#000;text-transform:uppercase;margin-bottom:1em}.marginalia ul{margin:0}.marginalia ul li{margin-bottom:.75em}.marginalia ul li:last-child{margin-bottom:0}.marginalia .story .story-link{text-decoration:none}.story.theme-summary .thumb{float:left;clear:left;margin:0 10px 0 0;width:75px;height:75px}.marginalia .story .thumb{position:relative;max-width:65px;width:21.67%;height:auto;clear:none;margin-left:0}.marginalia .story .thumb img{height:auto;width:auto}.marginalia .story .story-heading{color:#333;font-size:13px;font-size:.8125rem;line-height:17px;line-height:1.0625rem;font-weight:400;font-family:nyt-cheltenham-sh,georgia,times new roman,times,serif}.marginalia .story .thumb+.story-heading{float:left;clear:left;margin:0;width:74.5%;clear:right}.marginalia .story .story-heading .story-heading-text{padding-right:.75em}.marginalia .story .story-link .story-heading-text,.marginalia .story .story-link:hover{color:#326891}.marginalia .story .story-link:active .story-heading-text,.marginalia .story .story-link:hover .story-heading-text{text-decoration:underline}.related-coverage-marginalia{top:100%;position:absolute;right:0}.related-coverage,.story.theme-main .story-footer{padding:0 16px}.page-interactive .story.theme-main .story-header .story-meta .story-heading{font-size:41px;line-height:.97560975609756;text-align:center;font-weight:200}.page-interactive .story.theme-main .story-header .story-meta .story-heading:after{content:””;display:block;width:180px;height:1px;border-bottom:1px solid #ccc;margin:20px auto 10px}.page-interactive .story.theme-main .story-header .story-meta .story-meta-footer .summary{font-family:nyt-franklin,Arial,helvetica,sans-serif;font-size:14px;line-height:1.42857142857143;font-weight:500;color:#3f3f3f}.story.theme-main .dateline{font-family:nyt-franklin,Arial,helvetica,sans-serif;font-size:14px;line-height:1.42857142857143;font-weight:500;color:#7f7f7f}.viewport-medium-10 .story.theme-main .story-header{padding:0}.viewport-medium-10 #sharetools-interactive{display:block}.viewport-medium-10 .story.theme-main .sharetools-story{clear:left;display:block;float:left;position:relative;width:65px}.viewport-medium-10 .story.theme-main .sharetools-story >ul{position:absolute}.viewport-medium-10 .story.theme-main .sharetools.sharetools-story .sharetool.show-all-sharetool{margin-left:0}.viewport-medium-10 .comments-button.theme-kicker{display:inline-block}.viewport-medium-10 .story.theme-main .story-header{margin-top:16px;max-width:auto}.viewport-medium-10 .story.theme-main .story-header .story-meta{margin-bottom:10px}.viewport-medium-10 .story.theme-main .story-header .story-meta .story-heading{font-size:60px;text-align:center}.viewport-medium-10 .story.theme-main .story-header .story-meta .story-meta-footer .byline-dateline{text-align:center}.viewport-medium-10 .story.theme-main .story-header .story-meta .story-meta-footer .summary{text-align:center;margin-left:auto;margin-right:auto;margin-top:20px;max-width:720px;font-size:20px}.viewport-medium-10 .story.theme-main .story-header:after{margin-top:48px}.viewport-medium-10 .leadin-body{margin-bottom:16px;margin-left:105px;padding:0 0 32px;width:510px}.viewport-medium-10 .media.photo[data-media-action=modal]{pointer-events:auto}.viewport-medium-10 .marginalia{margin-top:720px}.viewport-medium-10 .related-coverage,.viewport-medium-10 .story.theme-main .story-footer{padding:0}.viewport-medium-10 .bottom-container-ads{display:none}.viewport-medium-10 .lede-container-ads{clear:right;display:none;float:right;position:relative}.viewport-medium-10 .lede-container-ads .ad{position:absolute;margin:0 0 40px 7px;top:0;right:0}.viewport-large .story.theme-main .story-header{max-width:1020px;margin:0 auto}.viewport-large .story.theme-main .story-header .story-meta .story-heading{max-width:80%;font-weight:200}.fade{opacity:0;transition:opacity .8s}.fade.faded{opacity:1}.fill-in-blank{display:inline-block;border-bottom:1px solid #000;width:100px}.cascade,.one-at-a-time,.quiz{margin-top:30px}.cascade .media img,.one-at-a-time .media img,.quiz .media img{width:100%;display:block}.cascade h2,.one-at-a-time h2,.quiz h2{font-size:24px;margin-top:2em;margin-bottom:1em}.cascade p,.one-at-a-time p,.quiz p{font-size:16px;line-height:1.4;font-weight:400;font-style:normal;font-family:georgia,times new roman,times,serif}@media only screen and (min-width:480px){.cascade p,.one-at-a-time p,.quiz p{font-size:17px;line-height:1.625rem}}.cascade >.media,.cascade >.video,.one-at-a-time >.media,.one-at-a-time >.video,.quiz >.media,.quiz >.video{margin-bottom:45px;width:100%;max-width:1020px;margin-left:auto;margin-right:auto}@media only screen and (min-width:480px){.cascade .conclusion,.cascade .response,.cascade >.text-block,.one-at-a-time .conclusion,.one-at-a-time .response,.one-at-a-time >.text-block,.quiz .conclusion,.quiz .response,.quiz >.text-block{max-width:600px;margin-left:auto;margin-right:auto;box-sizing:border-box}}.cascade .response,.one-at-a-time .response,.quiz .response{margin-top:2em}.cascade .conclusion >.text-block p:first-of-type,.one-at-a-time .conclusion >.text-block p:first-of-type,.quiz .conclusion >.text-block p:first-of-type{margin-top:1em}.done-button{display:block;text-align:center}.done-button >.text-block{display:inline-block;background-color:#fff;padding:10px 15px;border:1px solid #053e69;border-radius:3px;cursor:pointer;margin-top:10px;transition:all .35s ease-out;transition-property:padding,background-color}.done-button >.text-block p{margin-top:0;margin-bottom:0}.reset-block{margin-top:20px}.cascade >.reset-block,.one-at-a-time >.reset-block,.quiz >.reset-block{text-align:center}.clear-saved{font-family:nyt-franklin,Arial,helvetica,sans-serif;font-size:15px;line-height:1.5;cursor:pointer;background:#053e69;display:inline-block;border-radius:4px;padding:8px 20px;color:#fff}.clear-saved,.clear-saved:hover{text-decoration:none}.clear-saved p{margin-bottom:0}@media only screen and (min-width:480px){.reset-block{margin-top:50px}}.video .credit{font-size:14px}@media only screen and (min-width:480px){.step{max-width:600px;margin-left:auto;margin-right:auto;box-sizing:border-box}}.multiple-choice-question,.multiple-select-question{position:relative;border-bottom:1px solid #ccc;padding-top:23px;padding-bottom:34px}@media only screen and (min-width:480px){.multiple-choice-question,.multiple-select-question{padding-top:47px;padding-bottom:39px}}.multiple-choice-question p,.multiple-select-question p{font-size:16px;line-height:1.4;font-weight:400;font-style:normal;font-family:georgia,times new roman,times,serif;font-size:18px;line-height:1.625rem}@media only screen and (min-width:480px){.multiple-choice-question p,.multiple-select-question p{font-size:17px;line-height:1.625rem;font-size:20px;line-height:1.5}}.multiple-choice-question .counter,.multiple-select-question .counter{font-size:16px;line-height:1.4;font-weight:400;font-style:normal;font-family:georgia,times new roman,times,serif;font-size:20px;line-height:1.5;color:#656565;margin-bottom:12px}@media only screen and (min-width:480px){.multiple-choice-question .counter,.multiple-select-question .counter{font-size:17px;line-height:1.625rem}}.multiple-choice-question .media,.multiple-select-question .media{margin-bottom:14px}.multiple-choice-question .media img,.multiple-select-question .media img{width:100%}.multiple-choice-question .response,.multiple-select-question .response{border-left:1px solid rgba(0,0,0,.05);padding-left:19px}.multiple-choice-question .response p,.multiple-select-question .response p{font-size:16px;line-height:1.4;font-weight:400;font-style:normal;font-family:georgia,times new roman,times,serif;color:#777}@media only screen and (min-width:480px){.multiple-choice-question .response p,.multiple-select-question .response p{font-size:17px;line-height:1.625rem}}.multiple-choice-question .done-button,.multiple-select-question .done-button{text-align:center}.multiple-choice-question .done-button.is-complete,.multiple-select-question .done-button.is-complete{display:none}.multiple-choice-question.answering .done-button,.multiple-select-question.answering .done-button{display:block}.multiple-choice-question .answer,.multiple-select-question .answer{display:block;position:relative;padding:15px 20px;border-radius:3px;margin-top:10px;cursor:pointer;background:#eaf2f9;line-height:1.25;color:#053e69;transition:all .35s ease-out;transition-property:padding,background-color}.multiple-choice-question .answer p,.multiple-select-question .answer p{margin-top:0;margin-bottom:0}.multiple-choice-question.answered .answer,.multiple-select-question.answered .answer{color:#656565;cursor:default;background-color:#f7f7f7}.multiple-choice-question.answered .answer.selected,.multiple-select-question.answered .answer.selected{background-color:#9b9078;color:#fff}.multiple-choice-question.unanswered .answer.selected,.multiple-select-question.unanswered .answer.selected{background-color:#053e69;color:#fff}.multiple-choice-question.has-correct-answers .answer,.multiple-select-question.has-correct-answers .answer{background-size:19px 19px;background-position:calc(100% – 20px) 20px;background-repeat:no-repeat}.multiple-choice-question.answered.has-correct-answers .answer.selected,.multiple-select-question.answered.has-correct-answers .answer.selected{background-image:url(https://static01.nyt.com/inc/quiz-x_light.svg);background-color:#e27676;color:#fff}.multiple-choice-question.answered.has-correct-answers .answer.correct,.multiple-select-question.answered.has-correct-answers .answer.correct{background-image:url(https://int.nyt.com/assets/adventure/images/quiz-check_green.svg);color:#97c19a}.multiple-choice-question.answered.has-correct-answers .answer.selected.correct,.multiple-select-question.answered.has-correct-answers .answer.selected.correct{background-color:#95c198;background-image:url(https://static01.nyt.com/inc/quiz-check_light.svg);color:#fff}.multiple-choice-question .poll-answer,.multiple-choice-question .poll-answer p,.multiple-select-question .poll-answer,.multiple-select-question .poll-answer p{font-family:Arial,Helvetica,sans-serif}.multiple-choice-question .poll-answer-percentage,.multiple-select-question .poll-answer-percentage{float:right;font-size:16px;font-size:20px;line-height:1.5;font-weight:400;color:#bfbfbf}.multiple-choice-question .poll-answer-graph,.multiple-select-question .poll-answer-graph{position:absolute;left:0;top:1px;z-index:-1;height:calc(100% – 4px);background-color:#f2f2f2;transition:width .5s ease-in-out}.multiple-choice-question.unanswered .poll-answer-graph,.multiple-select-question.unanswered .poll-answer-graph{width:0!important}.multiple-choice-question.unanswered .poll-answer-percentage,.multiple-select-question.unanswered .poll-answer-percentage{display:none}.multiple-choice-question.answered .poll-answer,.multiple-select-question.answered .poll-answer{background-color:transparent}.multiple-choice-question.answered.has-correct-answers .poll-answer,.multiple-select-question.answered.has-correct-answers .poll-answer{color:#656565;padding-right:50px}.multiple-choice-question.answered.has-correct-answers .poll-answer.selected,.multiple-select-question.answered.has-correct-answers .poll-answer.selected{color:#f47851;background-color:transparent;background-image:url(https://static01.nyt.com/inc/quiz-x_red.svg)}.multiple-choice-question.answered.has-correct-answers .poll-answer.selected.correct,.multiple-select-question.answered.has-correct-answers .poll-answer.selected.correct{color:#f47851;background-color:transparent;background-image:url(https://int.nyt.com/assets/adventure/images/quiz-check_green.svg)}.multiple-choice-question.answered .answer.selected,.multiple-select-question.answered .answer.selected{background-color:transparent;color:#656565}.multiple-choice-question .stats p,.multiple-select-question .stats p{font-family:nyt-franklin,Arial,helvetica,sans-serif;font-weight:500;color:#666;text-align:right;font-size:14px}@media only screen and (min-width:480px){.multiple-choice-question .counter,.multiple-select-question .counter{border-bottom:0 solid #ccc;padding-top:23px;padding-bottom:0;font-size:20px}}@media only screen and (min-width:480px) and (min-width:480px){.multiple-choice-question .counter,.multiple-select-question .counter{padding-top:47px;padding-bottom:39px;padding-bottom:0;position:absolute;display:inline-block;width:180px;left:-210px;text-align:right;top:0}}@media only screen and (min-width:480px){.multiple-choice-question .answer.question-unanswered:hover,.multiple-choice-question .done-button >.text-block:hover,.multiple-select-question .answer.question-unanswered:hover,.multiple-select-question .done-button >.text-block:hover{background-color:#053e69;color:#fff}}@media only screen and (min-width:480px){.multiple-choice-question,.multiple-select-question{max-width:600px;margin-left:auto;margin-right:auto;box-sizing:border-box}}.scorecard{margin-top:2em;font-family:nyt-cheltenham,georgia,times new roman,times,serif}@media only screen and (min-width:480px){.scorecard{max-width:600px;margin-left:auto;margin-right:auto;box-sizing:border-box}}.scorecard .scorecard-kicker{line-height:1.5;font-size:20px;display:block;font-weight:400;color:#656565}.scorecard .scorecard-inner{font-size:18px;line-height:1.66;font-weight:700;color:#323232;text-align:left}.stats{margin-top:2em}@media only screen and (min-width:480px){.stats{max-width:600px;margin-left:auto;margin-right:auto;box-sizing:border-box}}.stats p{font-family:nyt-franklin,Arial,helvetica,sans-serif;font-weight:500;color:#666;text-align:right;font-size:14px}@media only screen and (min-width:480px){.scorecard .scorecard-kicker{float:left;width:180px;margin:7px 0 0 -210px;text-align:right;font-size:30px}.scorecard .scorecard-inner{font-size:36px;margin-bottom:12px}}.lede-question-adventure .multiple-choice-question,.lede-question-adventure .multiple-select-question{border-bottom:none}.lede-question-adventure .multiple-choice-question .counter,.lede-question-adventure .multiple-select-question .counter{display:none}.lede-question-adventure .multiple-choice-question .response,.lede-question-adventure .multiple-select-question .response{border-left:none;padding-left:0}.lede-question-adventure .multiple-choice-question .response p,.lede-question-adventure .multiple-select-question .response p{font-size:16px;line-height:1.4;font-weight:400;font-style:normal;font-family:georgia,times new roman,times,serif;color:#000}@media only screen and (min-width:480px){.lede-question-adventure .multiple-choice-question .response p,.lede-question-adventure .multiple-select-question .response p{font-size:17px;line-height:1.625rem}}.lede-question-adventure .multiple-choice-question .text-block.lede-question p,.lede-question-adventure .multiple-select-question .text-block.lede-question p{text-align:center;font-size:20px;margin-left:auto;margin-right:auto}@media only screen and (min-width:480px){.lede-question-adventure .multiple-choice-question .text-block.lede-question p,.lede-question-adventure .multiple-select-question .text-block.lede-question p{font-size:27px}}.chapter-header{font-size:36px;text-align:center}.chapter-header em,.chapter-header strong{display:block}.story.theme-main .story-header .story-meta .story-heading:before{content:” “;background-image:url(https://static01.nyt.com/images/2021/03/11/well/11Well-HealthQuiz-icon/11Well-HealthQuiz-icon-articleLarge.jpg);background-position:top;background-repeat:no-repeat;width:120px;height:120px;display:block;margin:0 auto 15px;background-size:cover}@media only screen and (min-width:480px){.story.theme-main .story-header .story-meta .story-heading:before{width:180px;height:180px}}1