Dental Enamel Hypoplasia

A study may shed light on tooth enamel development disruption by revealing a new children's autoimmune disorder that hinders proper tooth enamel development. The disorder is common in people with a rare genetic syndrome and in children with celiac disease. These findings could help develop strategies for early detection and prevention of the disorder. Enamel, the hardest and most mineral-rich substance in the human body, covers and protects our teeth. But in one of every 10 people -- and in one third of children with celiac disease -- this layer appears defective, failing to protect the teeth properly. As a result, teeth become more sensitive to heat, cold and sour food, and they may decay faster. In most cases, the cause of the faulty enamel production is unknown. Now, a study by Prof. Jakub Abramson and his team at the Weizmann Institute of Science, published recently in Nature, may shed light on this problem by revealing a new children's autoimmune disorder that hinders proper tooth enamel development. The disorder is common in people with a rare genetic syndrome and in children with celiac disease. These findings could help develop strategies for early detection and prevention of the disorder. Tooth enamel is made up primarily of mineral crystals that are gradually deposited on protein scaffolds during enamel development. Once the crystals are in place, the protein scaffold is dismantled, leaving behind a thin but exceptionally hard layer that covers and protects our teeth. A strange phenomenon was identified in people with a rare genetic disorder known as APS-1: Although the enamel layer of their milk teeth forms perfectly normally, something causes its faulty development in their permanent teeth. Since people with APS-1 suffer from a variety of autoimmune diseases, Abramson and his team hypothesized that the observed enamel defects may also be of an autoimmune nature -- in other words, that their immune system could be attacking their own proteins or cells that are necessary for enamel formation. In general, autoimmune diseases occur when the immune system's T cells or its antibodies mistakenly trigger an immune response against the body's own cells or tissues. To prevent these incidents of "friendly fire," T cells developing in the thymus gland need to first be educated to discriminate between the body's own proteins and those of foreign origin. To this end, T cells are presented with short segments of self-proteins that make up various tissues and organs in the body. When a "poorly educated" T cell erroneously identifies a self-protein in the thymus as a target for attack, that T cell is labeled as dangerous and destroyed, so that it could not cause any damage after being released from the thymus. This critical education step is impaired in APS-1 patients as a result of a mutation in a gene known as the autoimmune regulator (Aire). This gene is essential for the T cell education process: It produces a protein that is responsible for the collection of self-proteins presented to the T cells in the thymus. In their new study, scientists from Abramson's lab in Weizmann's Immunology and Regenerative Biology Department, led by research student Yael Gruper, sought to work out how mutations in the Aire gene lead to deficient tooth enamel production. The researchers discovered that, in the absence of Aire, proteins that play a key role in the development of enamel are not presented to the T cells in the thymus gland. As a result, T cells that are liable to identify these proteins as targets are released from the thymus, and they encourage the production of antibodies to the enamel proteins. But why do these autoantibodies damage permanent teeth and not baby teeth? The answer to this question lies in the fact that milk teeth develop in the embryonic stage, when the immune system is not yet fully formed and cannot create autoantibodies. In contrast, the development of enamel on permanent teeth starts at birth and continues until around the age of six, when the immune system is sufficiently mature to thwart enamel development. Furthermore, the researchers found a correlation between high levels of antibodies to enamel proteins and the severity of the harm to enamel development in children with APS-1. This strengthens the assumption that the presence of enamel-specific autoantibodies in childhood can potentially lead to dental problems. When the researchers looked into deficiencies in enamel development in people with other autoimmune diseases, they found a very similar phenomenon in children with celiac disease, a relatively common autoimmune disorder that affects around 1 percent of people in the West. When people with this disease are exposed to gluten, their immune system attacks and destroys the cellular layer lining the small intestine, leading to attacks on other self-proteins in the intestine. In an attempt to understand how celiac disease, known to cause intestinal damage, may also cause damage to tooth enamel, the researchers first examined whether people with this disease have autoantibodies that attack enamel. They found that a large proportion of celiac patients have these autoantibodies, just as do people with APS-1. But the "education" that takes place in the thymus gland of these patients seems normal, so why do they develop these antibodies? The researchers hypothesized that some proteins are found in both the intestine and the dental tissue and that these proteins play an important role in the development of tooth enamel. In this case, the antibodies that identify proteins in the intestine might move through the bloodstream to the dental tissue, where they could start to disrupt the enamel production process. Since many celiac patients had previously been found to develop sensitivity to cow's milk, the researchers decided to focus on the k-casein protein, a major component of dairy products. Strikingly, they found that the human equivalent of k-casein is one of the main components of the scaffold necessary for enamel formation. This led them to hypothesize that antibodies produced in the intestines of celiac patients in response to certain food antigens, such k-casein, may subsequently cause collateral damage to the development of enamel in the teeth, similarly to the way in which antibodies against gluten can eventually trigger autoimmunity against the intestine. Indeed, they discovered that most of the children diagnosed with celiac had high levels of antibodies against k-casein from cows' milk, which in many cases can also react against k-casein's human equivalent expressed in the enamel matrix. This means that in theory, the same antibodies that are produced in the intestine against the milk protein could act against the human k-casein in the teeth. These findings could have implications for the food industry. "Similarly to the lessons learned from gluten, we can assume that the consumption of large quantities of dairy products could lead to the production of antibodies against k-casein," Abramson explains. "This protein increases the amount of cheese that can be produced from milk, so the dairy industry deliberately raises its concentration in cow's milk. Our study, however, found that the milk k-casein is a potent immunogen, which may potentially trigger an immune response that can harm the body itself." Tooth enamel flaws are common, not just among people with celiac disease or APS-1. "Many people suffer from impaired tooth enamel development for unknown reasons," Abramson says. "It is possible that the new disorder we discovered, along with the possibility of diagnosing it in a blood or saliva test, will give their condition a name. Most important, early diagnosis in children may enable preventive treatment in the future."

Oral presentation highlights new findings about the efficacy of XACDURO® for the treatment of monomicrobial and polymicrobial Acinetobacter baumannii-calcoaceticus infections Researchers share global surveillance data on the in vitro activity of XERAVA® (eravacycline) for injection on resistant isolates and Gram-positive clinical pathogens Total of nine presentations on XACDURO® and XERAVA® to be revealed during IDWeek 2023 WALTHAM, Mass.--(BUSINESS WIRE)-- Innoviva Specialty Therapeutics, a subsidiary of Innoviva, Inc. (Nasdaq: INVA), announced today plans to present an oral abstract and four poster sessions from their portfolio of U.S. Food and Drug Administration (FDA)-approved critical care and infectious disease therapies at IDWeek 2023, October 11-15, held in Boston, MA. The company will deliver one oral abstract presentation and two poster sessions highlighting findings on their newly approved therapy, XACDURO® (sulbactam for injection; durlobactam for injection), co-packaged for intravenous use, which is the first and only antibiotic specifically developed to target the Acinetobacter pathogen in adults. XACDURO is indicated in adults for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) caused by susceptible isolates of Acinetobacter baumannii-calcoaceticus complex. In addition, four company-sponsored research studies on XACDURO will also be presented by the company’s research partners in poster sessions. “Antibiotic-resistant pathogens are one of the most significant and challenging threats to healthcare providers on the frontlines of infectious disease care,” said Margaret Koziel, MD, Chief Medical Officer, Innoviva Specialty Therapeutics. “IDWeek is an opportunity for us and for our research partners to share new clinical insights that help us better understand these therapies on a deeper level to improve treatment strategies.” Researchers from Innoviva Specialty Therapeutics will also present new surveillance data on XERAVA® (eravacycline), an anti-bacterial for the treatment of complicated intra-abdominal infections (cIAI) caused by multidrug-resistant bacteria during the scientific poster sessions. Company Presentations: Oral Abstract Presentation Efficacy of Sulbactam-Durlobactam (SUL-DUR) Compared to Colistin (COL) Against Acinetobacter baumannii-calcoaceticus Complex (ABC) Monomicrobial and Polymicrobial Infections in a Phase 3 Trial Authors: Alita A. Miller, Sarah M. McLeod, Adam Shapiro, Khurram Rana, David Altarac Innoviva Specialty Therapeutics, Waltham, MA, United States Session Date: Thursday, October 12, 2023; 10:30 – 10:45 AM ET Session Topic: Clinical Trials Session Location: 102 AB Poster Sessions Pharmacometric Analyses to Support Sulbactam-Durlobactam (SUL-DUR) Dosing Regimens in Patients with Altered Renal Function (2549) Authors: Kajal Larson, Sujata Bhavnani, Jeffrey Hammel, Anthony Cammarata, John O'Donnell, Christopher Rubino; Innoviva Specialty Therapeutics, Waltham, MA, United States, Institute for Clinical Pharmacodynamics, Inc. – Schenectady, NY United States Session Date: Saturday, October 14, 2023; 12:15 - 1:30 PM ET Session Topic: PK/PD Studies Session Location: Hall B + C In Vitro Susceptibility of Recent Clinical Isolates of P. aeruginosa and Enterobacterales to Imipenem or Meropenem Alone or in Combination with Sulbactam-Durlobactam (2138) Authors: Sarah M. McLeod, Nicole M. Carter, Samir H. Moussa, Alita A. Miller; Innoviva Specialty Therapeutics, Waltham, MA, United States Session Date: Saturday, October 14, 2023; 12:15 - 1:30 PM ET Session Topic: Antimicrobial Novel Agents Session Location: Hall B + C Surveillance of Eravacycline Against Enterobacterales and Non-Fermenter Clinical Isolates, Including Resistant Isolates, Collected Worldwide from Multiple Infection Sites During 2021 (2132) Authors: Stephen Hawser, Nimmi Kothari, Federica Monti, Tony Hodges, Kristie Zappas; IHMA Europe, Monthey (Valais), Switzerland; Innoviva Specialty Therapeutics, Inc, Waltham (MA), United States Session Date: Saturday, October 14, 2023; 12:15 – 1:30 PM ET Session Topic: Antimicrobial Novel Agents Session Location: Hall B + C Surveillance of Eravacycline Against Gram-Positive Clinical Pathogens, Including Resistant Isolates, Collected Worldwide From Multiple Infection Sites During 2021 (2133) Authors: Stephen Hawser, Nimmi Kothari, Federica Monti, Tony Hodges, Kristie Zappas; IHMA Europe, Monthey (Valais), Switzerland; Innoviva Specialty Therapeutics, Inc, Waltham (MA), United States Session Date: Saturday, October 14, 2023; 12:15 – 1:30 PM ET Session Topic: Antimicrobial Novel Agents Session Location: Hall B + C Company-Sponsored Research Presentations: Poster Sessions In vitro Synergy of the Combination of Sulbactam-Durlobactam and Cefepime at Clinically Relevant Concentrations Against A. baumannii, P. aeruginosa, and Enterobacterales (2121) Authors: Aliaa Fouad, PhD, David P. Nicolau, PharmD, FCCP, FIDSA, and Christian M. Gill, PharmD, Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, United States, Division of Infectious Diseases, Hartford Hospital, Hartford, CT United States Session Date: Saturday, October 14, 2023; 12:15 – 1:30 PM ET Session Topic: PK/PD Studies Session Location: Hall B + C Ex Vivo Assessment of Sulbactam-Durlobactam (SUL-DUR) Clearance During Continuous Renal Replacement Therapy (CRRT) (2526) Authors: Yasmeen Abouelhassan, Yuwei Shen, Xiaoyi Ye, David P Nicolau, Joseph L. Kuti Ctr. for Anti-Infect. Res. & Dev., Hartford Hospital, Hartford, CT Inpatient Hemo-Therapeutics, Hartford Hospital, Hartford, CT United States Session Date: Saturday, October 14, 2023; 12:15 – 1:30 PM ET Session Topic: New Antimicrobial Drug Development Session Location: Hall B + C (2515) Evaluation of the Equivalency of the Oxoid Sulbactam-Durlobactam (10/10µg) Antimicrobial Disc to the CLSI M07 Broth Microdilution Frozen Reference Method Authors: K. L. Hajek B.S., A.J Lovatt BSc., S. Bhalerao PhD., N. Khan BSc., D.T Staats M.S. M.M Hendrix B.S., N.M Holliday B.S., C.C Knapp M.S. Thermo Fisher Scientific, Cleveland, OH, United States; Thermo Fisher Scientific, Basingstoke, United Kingdom Session Date: Saturday, October 14, 2023; 12:15 – 1:30 PM Session Topic: New Antimicrobial Drug Development Session Location: Hall B + C (2517) Activity of Sulbactam-Durlobactam, Antibacterial Combinations, and Comparators Against a Challenge Set of 66 Acinetobacter Baumannii-Calcoaceticus Species Complex Isolates Authors: MD Huband, RE Mendes, G Bartleson, H Huynh, M Castanheira JMI Laboratories, North Liberty, IA, United States Session Date: Saturday, October 14, 2023; 12:15 – 1:30 PM Session Topic: New Antimicrobial Drug Development Session Location: Hall B + C About Acinetobacter Members of the Acinetobacter baumannii-calcoaceticus complex (Acinetobacter) are Gram-negative, opportunistic human pathogens that predominantly infect critically ill patients, often resulting in severe pneumonia and bloodstream infections.1 They can infect other body sites, such as the urinary tract and the skin.1 Acinetobacter is considered a global threat in the healthcare setting due in part to its ability to acquire multidrug resistance.2 Acinetobacter is resistant to penicillins and has also acquired resistance genes for almost all antibiotics used to treat Gram-negative bacteria, including fluoroquinolones, aminoglycosides, cephalosporins, and carbapenems.2 The Centers for Disease Control and Prevention (CDC) has identified carbapenem-resistant micro-organisms as an urgent threat.3 Globally, Acinetobacter baumannii was among the top six leading pathogens for deaths associated with resistance in 2019.4 Carbapenem-resistant Acinetobacter is considered a Priority 1 pathogen by the World Health Organization (WHO).5 In the U.S., there are more than 40,000 cases of Acinetobacter each year and approximately bout 40 percent of those are carbapenem-resistant.6,7 Globally, there are about a million cases each year of Acinetobacter, and about two-thirds of those are carbapenem-resistant Acinetobacter baumannii.6 More than 300,000 global deaths annually are associated with carbapenem-resistant Acinetobacter.4 About XACDURO® XACDURO® (sulbactam for injection; durlobactam for injection), co-packaged for intravenous use, is a combination of sulbactam, a beta-lactam antibacterial, and durlobactam, a beta-lactamase inhibitor, approved in patients 18 years of age and older for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) caused by susceptible isolates of Acinetobacter baumannii-calcoaceticus complex (Acinetobacter). XACDURO is not indicated for the treatment of HABP/VABP caused by pathogens other than susceptible isolates of Acinetobacter. XACDURO® INDICATION & USAGE Indication XACDURO® (sulbactam for injection; durlobactam for injection), co-packaged for intravenous use is indicated in adults for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) caused by susceptible isolates of Acinetobacter baumannii- calcoaceticus complex. Limitations of Use XACDURO is not indicated for the treatment of HABP/VABP caused by pathogens other than susceptible isolates of Acinetobacter baumannii-calcoaceticus complex. Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of XACDURO and other antibacterial drugs, XACDURO should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. IMPORTANT SAFETY INFORMATION Contraindications: XACDURO is contraindicated in patients with a history of known severe hypersensitivity to the components of XACDURO or other beta-lactam antibacterial drugs. Warnings and Precautions: Hypersensitivity was observed in patients treated with XACDURO in clinical trials. Serious and occasionally fatal hypersensitivity (anaphylactic) reactions and serious skin reactions have been reported in patients receiving beta-lactam antibacterial drugs. Before initiating therapy with XACDURO, careful inquiry should be made concerning previous hypersensitivity reactions to carbapenems, penicillins, cephalosporins, other beta lactams, and other allergens. If an allergic reaction occurs, discontinue XACDURO. Clostridioides difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents and may range in severity from mild diarrhea to fatal colitis. Evaluate if diarrhea occurs. If CDAD is suspected or confirmed, the risk/benefit of continuing treatment with XACDURO should be assessed. Prescribing XACDURO in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. Adverse Reactions: The most common adverse reactions reported in >10% of patients treated with XACDURO were liver test abnormalities (19%), diarrhea (17%), anemia (13%), and hypokalemia (12%). To report SUSPECTED ADVERSE REACTIONS, contact Innoviva Specialty Therapeutics, Inc. at 1-800-651-3861 or FDA at 1-800-FDA-1088 or . Before administering, please see the Full Prescribing Information for XACDURO. XERAVA® Important Safety Information Indications and Usage XERAVA is indicated for the treatment of complicated intra-abdominal infections (cIAI) caused by susceptible microorganisms: Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii, Enterobacter cloacae, Klebsiella oxytoca, Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, Streptococcus anginosus group, Clostridium perfringens, Bacteroides species, and Parabacteroides distasonis in patients 18 years or older. Limitations of Use XERAVA is not indicated for the treatment of complicated urinary tract infections (cUTI). Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of XERAVA and other antibacterial drugs, XERAVA should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. XERAVA is contraindicated for use in patients with known hypersensitivity to eravacycline, tetracycline-class antibacterial drugs, or to any of the excipients. Life-threatening hypersensitivity (anaphylactic) reactions have been reported with XERAVA. The use of XERAVA during tooth development (last half of pregnancy, infancy and childhood to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown) and enamel hypoplasia. The use of XERAVA during the second and third trimester of pregnancy, infancy and childhood up to the age of 8 years may cause reversible inhibition of bone growth. Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, and may range in severity from mild diarrhea to fatal colitis. The most common adverse reactions observed in clinical trials (incidence ≥3%) were infusion site reactions (7.7%), nausea (6.5%), and vomiting (3.7%). XERAVA is structurally similar to tetracycline-class antibacterial drugs and may have similar adverse reactions. Adverse reactions including photosensitivity, pseudotumor cerebri, and anti-anabolic action which has led to increased BUN, azotemia, acidosis, hyperphosphatemia, pancreatitis, and abnormal liver function tests, have been reported for other tetracycline-class antibacterial drugs, and may occur with XERAVA. Discontinue XERAVA if any of these adverse reactions are suspected. To report SUSPECTED ADVERSE REACTIONS, contact Innoviva Specialty Therapeutics, Inc., at 1-833-7-XERAVA (1-833-793-7282) or FDA at 1-800-FDA-1088 or Please see Full Prescribing Information for XERAVA. About Innoviva Specialty Therapeutics Innoviva Specialty Therapeutics, a subsidiary of Innoviva, Inc., is focused on delivering innovative therapies in critical care and infectious disease. Innoviva Specialty Therapeutics’ products, through its affiliate, La Jolla Pharmaceutical Company, include GIAPREZA® (angiotensin II), approved to increase blood pressure in adults with septic or other distributive shock, and XERAVA® (eravacycline) for the treatment of complicated intra-abdominal infections in adults. Innoviva Specialty Therapeutics’ products, through its affiliate, Entasis Therapeutics Inc., include XACDURO® (sulbactam for injection; durlobactam for injection), co-packaged for intravenous use approved for the treatment of adults with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia caused by susceptible strains of Acinetobacter baumannii-calcoaceticus complex (Acinetobacter). For more information about Innoviva Specialty Therapeutics, please visit here. About Innoviva Innoviva, Inc., is a diversified holding company with a portfolio of royalties and other healthcare assets, including Innoviva Specialty Therapeutics, a subsidiary focused on delivering innovative therapies in critical care and infectious disease. Innoviva’s royalty portfolio includes respiratory assets partnered with Glaxo Group Limited (GSK), including RELVAR®/BREO® ELLIPTA® (fluticasone furoate/vilanterol, FF/VI) and ANORO® ELLIPTA® (umeclidinium bromide/vilanterol, UMEC/VI). Under the Long-Acting Beta2 Agonist (LABA) Collaboration Agreement, Innoviva is entitled to receive royalties from GSK on sales of RELVAR®/BREO® ELLIPTA® and ANORO® ELLIPTA®. ANORO®, RELVAR® and BREO® are trademarks of the GSK group of companies. For more information on Innoviva, please visit here. Forward Looking Statements This press release contains certain “forward-looking” statements as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding, among other things, statements relating to goals, plans, objectives, and future events. Innoviva intends such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995. The words “anticipate”, “expect”, “goal”, “intend”, “objective”, “opportunity”, “plan”, “potential”, “target” and similar expressions are intended to identify such forward-looking statements. Such forward-looking statements involve substantial risks, uncertainties, and assumptions. These statements are based on the current estimates and assumptions of the management of Innoviva as of the date of this press release and are subject to known and unknown risks, uncertainties, changes in circumstances, assumptions and other factors that may cause the actual results of Innoviva to be materially different from those reflected in the forward-looking statements. Important factors that could cause actual results to differ materially from those indicated by such forward-looking statements include, among others, risks related to: expected cost savings; lower than expected future royalty revenue from respiratory products partnered with GSK; the commercialization of RELVAR®/BREO® ELLIPTA®, ANORO® ELLIPTA® and, formerly, TRELEGY® ELLIPTA® in the jurisdictions in which these products have been approved; the strategies, plans and objectives of Innoviva (including Innoviva’s growth strategy and corporate development initiatives beyond the existing respiratory portfolio); the timing, manner, and amount of potential capital returns to shareholders; the status and timing of clinical studies, data analysis and communication of results; the potential benefits and mechanisms of action of product candidates; expectations for product candidates through development and commercialization; the timing of regulatory approval of product candidates; and projections of revenue, expenses and other financial items; the impact of the novel coronavirus (COVID-19). Other risks affecting Innoviva are described under the headings “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” contained in Innoviva’s Annual Report on Form 10-K for the year ended December 31, 2022 and Quarterly Reports on Form 10-Q, which are on the Securities and Exchange Commission (SEC) and available on the SEC’s website at . Past performance is not necessarily indicative of future results. No forward-looking statements can be guaranteed, and actual results may differ materially from such statements. Given these uncertainties, you should not place undue reliance on these forward-looking statements. The information in this press release is provided only as of the date hereof, and Innoviva assumes no obligation to update its forward-looking statements on account of new information, future events or otherwise, except as required by law. References 1 Ballouz T, Aridi J, Afif C, et al. (2017) Risk Factors, Clinical Presentation, and Outcome of Acinetobacter baumannii Bacteremia. Front. Cell. Infect. Microbiol. 7:156. doi: 10.3389/fcimb.2017.00156 2 Kyriakidis I, Vasileiou E, Pana ZD, Tragiannidis A. Acinetobacter baumannii Antibiotic Resistance Mechanisms. Pathogens. 2021 Mar 19;10(3):373. doi: 10.3390/pathogens10030373. PMID: 33808905; PMCID: PMC8003822. 3 Centers for Disease Control and Prevention, “Carbapenem-resistant Acinetobacter baumannii (CRAB): An urgent public health threat in United States healthcare facilities,” August 2021: . Accessed: August 7, 2023 4 Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet. 2022; 399(10325):629-655. (21)02724-0/fulltext 5 World Health Organization, “WHO publishes list of bacteria for which new antibiotics are urgently needed,” February 27, 2017: . Accessed: August 7, 2023 6 Spellberg B, Rex JH. The Value of Single-Pathogen Antibacterial Agents. National Review Drug Discovery. 2013 Dec;12(12):963. doi: 10.1038/nrd3957-c1. Epub 2013 Nov 15. 7 Gupta V, Ye G, Olesky M, Lawrence K, Murray J, Yu K. National prevalence estimates for resistant Enterobacteriaceae and Acinetobacter species in hospitalized patients in the United States. Int J Infect Dis. 2019 Aug;85:203-211. doi: 10.1016/j.ijid.2019.06.017. Epub 2019 Jun 20. PMID: 31229615.

Using archaeological findings and survey data on contemporary gender attitudes, political scientists find individuals who live in areas that historically favored men over women display more pro-male bias today than those who live in places where gender relations were more egalitarian centuries ago. Findings speak to the power of cultural transmission of gender norms. New research from Washington University in St. Louis provides evidence that modern gender norms and biases in Europe have deep historical roots dating back to the Middle Ages and beyond, suggesting that DNA is not the only thing we inherit from our ancestors. The findings -- published on March 13, 2023 in the Proceedings of the National Academy of Sciences (PNAS) -- highlight why gender norms have remained stubbornly persistent in many parts of the world despite significant strides made by the international women's rights movement over the last 100-150 years. Using dental records of more than 10,000 people from 139 archaeological sites throughout Europe, researchers found that individuals who live in areas that historically favored men over women display more pro-male bias today than those who live in places where gender relations were more egalitarian centuries ago -- evidence that gender attitudes are "transmitted" or handed down from generation to generation. These biases outlasted monumental socioeconomic and political changes such as industrialization and world wars. Researchers found one exception to the rule, however: In regions that experienced abrupt, large-scale population replacement -- such as a pandemic or natural disaster -- transmission of these values was interrupted. "The median age of the skeletons in this study is about 1,000 years dating back to the medieval era. It is therefore remarkable that the patterns of gender bias that existed during those times and earlier are still replicated in contemporary attitudes," said Margit Tavits, the Dr. William Taussig Professor in Arts & Sciences at WashU. "Given the enormous social, economic and political changes that have taken place in Europe during this time, our findings speak to the power of cultural transmission of gender norms." The incredible stability of these norms over hundreds, if not thousands, of years also explains why it has been difficult in some regions to move the needle toward gender equality. "There has been a widespread belief that gender norms are a byproduct of structural and institutional factors like religion and agricultural practices. Our findings draw attention to the fact that gender-equal norms passed down from one generation to the next can persist even if institutions or structures incentivize inequality, and vice versa," Tavits said. "For those working to foster gender equality, the message from our research is that rules and policies are not going to be enough to undermine deeply rooted sexist beliefs and sustain equal ones. We must also address the cultural forces channeling these beliefs." Taylor Damann and Jeremy Siow -- doctoral students in the Department of Political Science at WashU -- conducted research and co-authored the paper with Tavits. About the research Previous archaeological research has used linear enamel hypoplasias -- permanent lesions on the teeth caused by trauma, malnutrition or disease -- to analyze prehistoric gender equality. Because the lesions form exclusively in cases of sustained bodily stress, their presence or absence can tell researchers a great deal about the person's health and living conditions. Further, differences between male and female teeth at the same location are an indication of which sex received preferential treatment in terms of health care and dietary resources at the time. According to Tavits, studying gender norms in Europe is advantageous given the relative similarity of various institutional and environmental conditions across the region. This allowed researchers to control for factors that could affect modern gender attitudes, such as religion and political institutions. Because differences in gender attitudes are fairly small across the continent, compared with the rest of the world, this setting also set a higher bar for detecting significant associations between historical and contemporary attitudes. Yet, time and time again, researchers found evidence of this association. For example, individuals living in an area that was historically egalitarian were 20% more likely to have pro-female attitudes than people living in areas that were historically the most pro-male. Additional tests showed that historical gender bias failed to predict modern gender attitudes for immigrant populations. Researchers also found no evidence of historical gender bias impacting contemporary attitudes in areas hardest hit by the bubonic plague of the 14th century. Finally, they looked to the United States, where the arrival of European settlers in the 16th century led to large-scale displacement of Native Americans. Once again, they found no association between historical and current gender norms. "Together, these findings provide further support for the idea that historical biases persist because they are passed down from one generation to the next and occur only when the transmission across generations is not interrupted. We were surprised that such a clear relationship emerged," Tavits said. A tale of two cities In the paper, Tavits, Damann and Siow highlight two archaeological sites to illustrate how the contrasting historical treatment of women relative to men is reflected in current gender attitudes. At the first site in Istria, a small urban Greek settlement on the Black Sea in the modern Dobruja region of Romania, researchers found evidence of a pro-male bias in historical dental records dating back to around 550 A.D. Out of the 49 skeletons for whom sex and dental information could be extracted, 58% of females show signs of malnutrition and trauma in their teeth, while only 25% of males do. According to the authors, the status of men and women in society today has remained relatively unequal in the southeastern region of Romania, based on modern indicators of gender equality. For example, they note, only 52.5% of women participate in the labor market compared with 78% of men, and only 18% of the representatives in the modern municipal council are women. The population's beliefs about gender norms are similarly unequal, they write. More than half of the residents believe that men have more of a right to jobs than women and there is near consensus (89%) that a woman must have children to be fulfilled. Contrast this with Plinkaigalis, a rural community in modern-day western Lithuania made up of a population of Balts. Unlike Istria, Plinkaigalis favored women's health. Of the 157 skeletons at this site -- also dating back to 550 A.D. -- 56% of males show dental signals of trauma and malnutrition whereas only 46% of females do. Separate studies have also found evidence that gender norms here were favorable to women. In the modern era, this location, now called Ke ?dainiai, remains relatively gender equal. Employment levels in western Lithuanian do not vary strongly by gender: 76% men vs. 72.7% women. And women are nearly proportionally represented in local politics (48%). Likewise, less than a quarter of residents of the modern location believe men have more of a right to a job than women, and 56% believe women need children to be fulfilled. "In sum, the parallels between historical and modern gender norms at both of these locations are stark and in line with our argument about persistence," the authors wrote. "The male preference at Istria, dating back at least to the early medieval era, is still reflected in unequal gender relations today. The area around pre-medieval Plinkaigalis, on the other hand, continues to treat men and women with relative equality as (according to skeletal records) it did about 1,500 years ago."