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Importance: Iron deficiency is the leading cause of anemia during pregnancy. According to survey data from 1999 to 2006, overall estimated prevalence of iron deficiency during pregnancy is near 18% and increases across the 3 trimesters of pregnancy (from 6.9% to 14.3% to 28.4%). An estimated 5% of pregnant persons have iron deficiency anemia., Objective: The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the evidence on the benefits and harms of screening and supplementation for iron deficiency with and without anemia on maternal and infant health outcomes in asymptomatic pregnant persons., Population: Asymptomatic pregnant adolescents and adults., Evidence Assessment: The USPSTF concludes that the current evidence is insufficient, and the balance of benefits and harms of screening for iron deficiency and iron deficiency anemia in asymptomatic pregnant persons on maternal and infant health outcomes cannot be determined. The USPSTF also concludes that the current evidence is insufficient, and the balance of benefits and harms of iron supplementation in asymptomatic pregnant persons on maternal and infant health outcomes cannot be determined., Recommendation: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for iron deficiency and iron deficiency anemia in pregnant persons to prevent adverse maternal and infant health outcomes. (I statement) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of routine supplementation for iron deficiency and iron deficiency anemia in pregnant persons to prevent adverse maternal and infant health outcomes. (I statement).

Importance: Approximately 19.7% of children and adolescents aged 2 to 19 years in the US have a body mass index (BMI) at or above the 95th percentile for age and sex, based on Centers for Disease Control and Prevention growth charts from 2000. The prevalence of high BMI increases with age and is higher among Hispanic/Latino, Native American/Alaska Native, and non-Hispanic Black children and adolescents and children from lower-income families., Objective: The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the evidence on interventions (behavioral counseling and pharmacotherapy) for weight loss or weight management in children and adolescents that can be provided in or referred from a primary care setting., Population: Children and adolescents 6 years or older., Evidence Assessment: The USPSTF concludes with moderate certainty that providing or referring children and adolescents 6 years or older with a high BMI to comprehensive, intensive behavioral interventions has a moderate net benefit., Recommendation: The USPSTF recommends that clinicians provide or refer children and adolescents 6 years or older with a high BMI (≥95th percentile for age and sex) to comprehensive, intensive behavioral interventions. (B recommendation).

Importance: Falls are the leading cause of injury-related morbidity and mortality among older adults in the US. In 2018, 27.5% of community-dwelling adults 65 years or older reported at least 1 fall in the past year and 10.2% reported a fall-related injury. In 2021, an estimated 38 742 deaths resulted from fall-related injuries., Objective: The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the effectiveness and harms of primary care-relevant interventions to prevent falls and fall-related morbidity and mortality in community-dwelling adults 65 years or older., Population: Community-dwelling adults 65 years or older at increased risk of falls., Evidence Assessment: The USPSTF concludes with moderate certainty that exercise interventions provide a moderate net benefit in preventing falls and fall-related morbidity in older adults at increased risk for falls. The USPSTF concludes with moderate certainty that multifactorial interventions provide a small net benefit in preventing falls and fall-related morbidity in older adults at increased risk for falls., Recommendation: The USPSTF recommends exercise interventions to prevent falls in community-dwelling adults 65 years or older who are at increased risk for falls. (B recommendation) The USPSTF recommends that clinicians individualize the decision to offer multifactorial interventions to prevent falls to community-dwelling adults 65 years or older who are at increased risk for falls. Existing evidence indicates that the overall net benefit of routinely offering multifactorial interventions to prevent falls is small. When determining whether this service is appropriate for an individual, patients and clinicians should consider the balance of benefits and harms based on the circumstances of prior falls, presence of comorbid medical conditions, and the patient's values and preferences. (C recommendation).

Importance: The United States Preventive Services Task Force (USPSTF) has considered the topic of prevention of child maltreatment multiple times over its nearly 40-year history, each time reaching the conclusion that the evidence is insufficient to recommend for or against interventions aimed at preventing this important health problem with significant negative sequelae before it occurs. In the most recent evidence review, which was conducted from August 2021 to November 2023 and published in March 2024, the USPSTF considered contextual questions on the evidence for bias in reporting and diagnosis of maltreatment in addition to key questions regarding effectiveness of interventions to prevent child maltreatment., Observations: A comprehensive literature review found evidence of inaccuracies in risk assessment and racial and ethnic bias in the reporting of child maltreatment and in the evaluation of injuries concerning for maltreatment, such as skull fractures. When children are incorrectly identified as being maltreated, harms, such as unnecessary family separation, may occur. Conversely, when children who are being maltreated are missed, harms, such as ongoing injury to the child, continue. Interventions focusing primarily on preventing child maltreatment did not demonstrate consistent benefit or information was insufficient. Additionally, the interventions may expose children to the risk of harm as a result of these inaccuracies and biases in reporting and evaluation. These inaccuracies and biases also complicate assessment of the evidence for making clinical prevention guidelines., Conclusions and Relevance: There are several potential strategies for consideration in future efforts to evaluate interventions aimed at the prevention of child maltreatment while minimizing the risk of exposing children to known biases in reporting and diagnosis. Promising strategies to explore might include a broader array of outcome measures for addressing child well-being, using population-level metrics for child maltreatment, and assessments of policy-level interventions aimed at improving child and family well-being. These future considerations for research in addressing child maltreatment complement the USPSTF's research considerations on this topic. Both can serve as guides to researchers seeking to study the ways in which we can help all children thrive.

Gene-editing technologies promise to create a new class of therapeutics that can achieve permanent correction with a single intervention. Besides eliminating mutant alleles in familial disease, gene-editing can also be used to favorably manipulate upstream pathophysiologic events and alter disease-course in wider patient populations, but few such feasible therapeutic avenues have been reported. Here we use CRISPR-Cas9 to edit the last exon of amyloid precursor protein ( App ), relevant for Alzheimer's disease (AD). Our strategy effectively eliminates an endocytic (YENPTY) motif at APP C-terminus, while preserving the N-terminus and compensatory APP-homologues. This manipulation favorably alters events along the amyloid-pathway - inhibiting toxic APP-β-cleavage fragments (including Aβ) and upregulating neuroprotective APP-α-cleavage products. AAV-driven editing ameliorates neuropathologic, electrophysiologic, and behavioral deficits in an AD knockin mouse model. Effects persist for many months, and no abnormalities are seen in WT mice even after germline App -editing; underlining overall efficacy and safety. Pathologic alterations in the glial-transcriptome of App -KI mice, as seen by single nuclei RNA-sequencing (sNuc-Seq), are also normalized by App C-terminus editing. Our strategy takes advantage of innate transcriptional rules that render terminal exons insensitive to nonsense-decay, and the upstream manipulation is expected to be effective for all forms of AD. These studies offer a path for a one-time disease-modifying treatment for AD., Competing Interests: Competing interest declaration: S.R. is the scientific co-founder and owns equity in CRISPRAlz.

Importance: Speech and language delays and disorders can pose significant problems for children and their families. Evidence suggests that school-aged children with speech or language delays may be at increased risk of learning and literacy disabilities, including difficulties with reading and writing., Objective: The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate benefits and harms of screening for speech and language delay and disorders in children 5 years or younger., Population: Asymptomatic children 5 years or younger whose parents or clinicians do not have specific concerns about their speech, language, hearing, or development., Evidence Assessment: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for speech and language delay and disorders in children who do not present with signs or symptoms or parent/caregiver concerns., Recommendation: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for speech and language delay and disorders in children 5 years or younger without signs or symptoms. (I statement).

Importance: Oral health is fundamental to health and well-being across the life span. Dental caries (cavities) and periodontal disease (gum disease) are common and often untreated oral health conditions that affect eating, speaking, learning, smiling, and employment potential. Untreated oral health conditions can lead to tooth loss, irreversible tooth damage, and other serious adverse health outcomes., Objective: The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate screening and preventive interventions for oral health conditions in adults., Population: Asymptomatic adults 18 years or older., Evidence Assessment: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for oral health conditions (eg, dental caries or periodontal disease) performed by primary care clinicians in asymptomatic adults. The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of preventive interventions for oral health conditions (eg, dental caries or periodontal disease) performed by primary care clinicians in asymptomatic adults., Recommendations: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of routine screening performed by primary care clinicians for oral health conditions, including dental caries or periodontal-related disease, in adults. (I statement) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of preventive interventions performed by primary care clinicians for oral health conditions, including dental caries or periodontal-related disease, in adults. (I statement).

Importance: Oral health is fundamental to health and well-being across the lifespan. Oral health conditions affect the daily lives of school-age children and adolescents, leading to loss of more than 51 million school hours every year. Untreated oral health conditions in children can lead to serious infections and affect growth, development, and quality of life., Objective: The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate screening and preventive interventions for oral health conditions in children and adolescents aged 5 to 17 years., Population: Asymptomatic children and adolescents aged 5 to 17 years., Evidence Assessment: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for oral health conditions (eg, dental caries) performed by primary care clinicians in asymptomatic children and adolescents aged 5 to 17 years. The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of preventive interventions for oral health conditions (eg, dental caries) performed by primary care clinicians in asymptomatic children and adolescents aged 5 to 17 years., Recommendations: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of routine screening performed by primary care clinicians for oral health conditions, including dental caries, in children and adolescents aged 5 to 17 years. (I statement) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of preventive interventions performed by primary care clinicians for oral health conditions, including dental caries, in children and adolescents aged 5 to 17 years. (I statement).

Influenza A Virus (IAV) is a recurring respiratory virus with limited availability of antiviral therapies. Understanding host proteins essential for IAV infection can identify targets for alternative host-directed therapies (HDTs). Using affinity purification-mass spectrometry and global phosphoproteomic and protein abundance analyses using three IAV strains (pH1N1, H3N2, H5N1) in three human cell types (A549, NHBE, THP-1), we map 332 IAV-human protein-protein interactions and identify 13 IAV-modulated kinases. Whole exome sequencing of patients who experienced severe influenza reveals several genes, including scaffold protein AHNAK, with predicted loss-of-function variants that are also identified in our proteomic analyses. Of our identified host factors, 54 significantly alter IAV infection upon siRNA knockdown, and two factors, AHNAK and coatomer subunit COPB1, are also essential for productive infection by SARS-CoV-2. Finally, 16 compounds targeting our identified host factors suppress IAV replication, with two targeting CDK2 and FLT3 showing pan-antiviral activity across influenza and coronavirus families. This study provides a comprehensive network model of IAV infection in human cells, identifying functional host targets for pan-viral HDT., (© 2023. Springer Nature Limited.)

Importance: Hypertensive disorders of pregnancy are among the leading causes of maternal morbidity and mortality in the US. The rate of hypertensive disorders of pregnancy has been increasing from approximately 500 cases per 10 000 deliveries in 1993 to 1021 cases per 10 000 deliveries in 2016 to 2017., Objective: The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the benefits and harms of screening for hypertensive disorders of pregnancy., Population: Pregnant persons without a known diagnosis of a hypertensive disorder of pregnancy or chronic hypertension., Evidence Assessment: The USPSTF concludes with moderate certainty that screening for hypertensive disorders in pregnancy with blood pressure measurements has substantial net benefit., Recommendation: The USPSTF recommends screening for hypertensive disorders in pregnant persons with blood pressure measurements throughout pregnancy. (B recommendation).

Importance: Neural tube defects are among the most common congenital malformations in the US, with an estimated 3000 pregnancies affected each year. Many of these neural tube defects are caused by low folate levels in the body., Objective: The US Preventive Services Task Force (USPSTF) commissioned a reaffirmation evidence update on the benefits and harms of folic acid supplementation., Population: Persons who are planning to or could become pregnant., Evidence Assessment: The USPSTF concludes that, for persons who are planning to or could become pregnant, there is high certainty that folic acid supplementation has a substantial net benefit to prevent neural tube defects in their offspring., Recommendation: The USPSTF recommends that all persons planning to or who could become pregnant take a daily supplement containing 0.4 to 0.8 mg (400 to 800 μg) of folic acid. (A recommendation).

Importance: Familial hypercholesterolemia and multifactorial dyslipidemia are 2 conditions that cause abnormally high lipid levels in children, which can lead to premature cardiovascular events (eg, myocardial infarction and stroke) and death in adulthood., Objective: The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the benefits and harms of screening for lipid disorders in asymptomatic children and adolescents., Population: Asymptomatic children and adolescents 20 years or younger without a known diagnosis of a lipid disorder., Evidence Assessment: The USPSTF concludes that the current evidence is insufficient and the balance of benefits and harms for screening for lipid disorders in asymptomatic children and adolescents 20 years or younger cannot be determined., Recommendation: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for lipid disorders in children and adolescents 20 years or younger. (I statement).

Importance: Anxiety disorders are commonly occurring mental health conditions. They are often unrecognized in primary care settings and substantial delays in treatment initiation occur., Objective: The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the benefits and harms of screening for anxiety disorders in asymptomatic adults., Population: Asymptomatic adults 19 years or older, including pregnant and postpartum persons. Older adults are defined as those 65 years or older., Evidence Assessment: The USPSTF concludes with moderate certainty that screening for anxiety disorders in adults, including pregnant and postpartum persons, has a moderate net benefit. The USPSTF concludes that the evidence is insufficient on screening for anxiety disorders in older adults., Recommendation: The USPSTF recommends screening for anxiety disorders in adults, including pregnant and postpartum persons. (B recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for anxiety disorders in older adults. (I statement).

Importance: In the US, tuberculosis remains an important preventable disease, including active tuberculosis, which may be infectious, and latent tuberculosis infection (LTBI), which is asymptomatic and not infectious but can later progress to active disease. The precise prevalence rate of LTBI in the US is difficult to determine; however, estimated prevalence is about 5.0%, or up to 13 million persons. Incidence of tuberculosis varies by geography and living accommodations, suggesting an association with social determinants of health., Objective: To update its 2016 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review on LTBI screening and treatment in asymptomatic adults seen in primary care, as well as the accuracy of LTBI screening tests., Population: Asymptomatic adults 18 years or older at increased risk for tuberculosis., Evidence Assessment: The USPSTF concludes with moderate certainty that there is a moderate net benefit in preventing active tuberculosis disease by screening for LTBI in persons at increased risk for tuberculosis infection., Recommendation: The USPSTF recommends screening for LTBI in populations at increased risk. (B recommendation).

Importance: Skin cancer is the most commonly diagnosed cancer in the US. There are different types of skin cancer varying in disease incidence and severity. Basal and squamous cell carcinomas are the most common types of skin cancer but infrequently lead to death or substantial morbidity. Melanomas represent about 1% of skin cancer and cause the most skin cancer deaths. Melanoma is about 30 times more common in White persons than in Black persons. However, persons with darker skin color are often diagnosed at later stages, when skin cancer is more difficult to treat., Objective: To update its 2016 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review on the benefits and harms of screening for skin cancer in asymptomatic adolescents and adults., Population: Asymptomatic adolescents and adults who do not have a history of premalignant or malignant skin lesions., Evidence Assessment: The USPSTF concludes that the evidence is insufficient to determine the balance of benefits and harms of visual skin examination by a clinician to screen for skin cancer in asymptomatic adolescents and adults., Recommendation: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of visual skin examination by a clinician to screen for skin cancer in adolescents and adults. (I statement).

Importance: Genital herpes is a common sexually transmitted infection caused by 2 related viruses, herpes simplex type 1 (HSV-1) and herpes simplex type 2 (HSV-2). Infection is lifelong; currently, there is no cure for HSV infection. Antiviral medications may provide clinical benefits to symptomatic persons. Transmission of HSV from a pregnant person to their infant can occur, most commonly during delivery; when genital lesions or prodromal symptoms are present, cesarean delivery can reduce the risk of transmission. Neonatal herpes infection is uncommon yet can result in substantial morbidity and mortality., Objective: To reaffirm its 2016 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a reaffirmation evidence update on targeted key questions to systematically evaluate the evidence on accuracy, benefits, and harms of routine serologic screening for HSV-2 infection in asymptomatic adolescents, adults, and pregnant persons., Population: Adolescents and adults, including pregnant persons, without known history, signs, or symptoms of genital HSV infection., Evidence Assessment: The USPSTF concludes with moderate certainty that the harms outweigh the benefits for population-based screening for genital HSV infection in asymptomatic adolescents and adults, including pregnant persons., Recommendation: The USPSTF recommends against routine serologic screening for genital HSV infection in asymptomatic adolescents and adults, including pregnant persons. (D recommendation).

Importance: Current prevalence of obstructive sleep apnea (OSA) in the US is not well established; however, based on cohort and survey data, in 2007-2010 the estimated prevalence of at least mild OSA (defined as an apnea-hypoxia index [AHI] ≥5) plus symptoms of daytime sleepiness among adults aged 30 to 70 years was 14% for men and 5% for women, and the estimated prevalence of moderate to severe OSA (defined as AHI ≥15) was 13% for men and 6% for women. Severe OSA is associated with increased all-cause mortality. Other adverse health outcomes associated with untreated OSA include cardiovascular disease and cerebrovascular events, type 2 diabetes, cognitive impairment, decreased quality of life, and motor vehicle crashes., Objective: To update its 2017 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the benefits and harms of screening for OSA in adults., Population: Asymptomatic adults (18 years or older) and adults with unrecognized symptoms of OSA., Evidence Assessment: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for OSA in the general adult population., Recommendation: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for OSA in the general adult population. (I statement).

Importance: Menopause is defined as the cessation of a person's menstrual cycle. It is defined retrospectively, 12 months after the final menstrual period. Perimenopause, or the menopausal transition, is the few-year time period preceding a person's final menstrual period and is characterized by increasing menstrual cycle length variability and periods of amenorrhea, and often symptoms such as vasomotor dysfunction. The prevalence and incidence of most chronic diseases (eg, cardiovascular disease, cancer, osteoporosis, and fracture) increase with age, and US persons who reach menopause are expected on average to live more than another 30 years., Objective: To update its 2017 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the benefits and harms of systemic (ie, oral or transdermal) hormone therapy for the prevention of chronic conditions in postmenopausal persons and whether outcomes vary by age or by timing of intervention after menopause., Population: Asymptomatic postmenopausal persons who are considering hormone therapy for the primary prevention of chronic medical conditions., Evidence Assessment: The USPSTF concludes with moderate certainty that the use of combined estrogen and progestin for the primary prevention of chronic conditions in postmenopausal persons with an intact uterus has no net benefit. The USPSTF concludes with moderate certainty that the use of estrogen alone for the primary prevention of chronic conditions in postmenopausal persons who have had a hysterectomy has no net benefit., Recommendation: The USPSTF recommends against the use of combined estrogen and progestin for the primary prevention of chronic conditions in postmenopausal persons. (D recommendation) The USPSTF recommends against the use of estrogen alone for the primary prevention of chronic conditions in postmenopausal persons who have had a hysterectomy. (D recommendation).

Importance: Depression is a leading cause of disability in the US. Children and adolescents with depression typically have functional impairments in their performance at school or work as well as in their interactions with their families and peers. Depression can also negatively affect the developmental trajectories of affected youth. Major depressive disorder (MDD) in children and adolescents is strongly associated with recurrent depression in adulthood; other mental disorders; and increased risk for suicidal ideation, suicide attempts, and suicide completion. Suicide is the second-leading cause of death among youth aged 10 to 19 years. Psychiatric disorders and previous suicide attempts increase suicide risk., Objective: To update its 2014 and 2016 recommendations, the US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the benefits and harms of screening, accuracy of screening, and benefits and harms of treatment of MDD and suicide risk in children and adolescents that would be applicable to primary care settings., Population: Children and adolescents who do not have a diagnosed mental health condition or are not showing recognized signs or symptoms of depression or suicide risk., Evidence Assessment: The USPSTF concludes with moderate certainty that screening for MDD in adolescents aged 12 to 18 years has a moderate net benefit. The USPSTF concludes that the evidence is insufficient on screening for MDD in children 11 years or younger. The USPSTF concludes that the evidence is insufficient on the benefit and harms of screening for suicide risk in children and adolescents owing to a lack of evidence., Recommendation: The USPSTF recommends screening for MDD in adolescents aged 12 to 18 years. (B recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for MDD in children 11 years or younger. (I statement) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for suicide risk in children and adolescents. (I statement).

Importance: Anxiety disorder, a common mental health condition in the US, comprises a group of related conditions characterized by excessive fear or worry that present as emotional and physical symptoms. The 2018-2019 National Survey of Children's Health found that 7.8% of children and adolescents aged 3 to 17 years had a current anxiety disorder. Anxiety disorders in childhood and adolescence are associated with an increased likelihood of a future anxiety disorder or depression., Objective: The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the benefits and harms of screening for anxiety disorders in children and adolescents. This is a new recommendation., Population: Children and adolescents 18 years or younger who do not have a diagnosed anxiety disorder or are not showing recognized signs or symptoms of anxiety., Evidence Assessment: The USPSTF concludes with moderate certainty that screening for anxiety in children and adolescents aged 8 to 18 years has a moderate net benefit. The USPSTF concludes that the evidence is insufficient on screening for anxiety in children 7 years or younger., Recommendation: The USPSTF recommends screening for anxiety in children and adolescents aged 8 to 18 years. (B recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for anxiety in children 7 years or younger. (I statement).

Importance: Syphilis is a sexually transmitted infection that can progress through different stages (primary, secondary, latent, and tertiary) and cause serious health problems if left untreated. Reported cases of primary and secondary syphilis in the US increased from a record low of 2.1 cases per 100 000 population in 2000 and 2001 to 11.9 cases per 100 000 population in 2019. Men account for the majority of cases (83% of primary and secondary syphilis cases in 2019), and rates among women nearly tripled from 2015 to 2019., Objective: To reaffirm its 2016 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a reaffirmation evidence update focusing on targeted key questions evaluating the performance of risk assessment tools and the benefits and harms of screening for syphilis in nonpregnant adolescents and adults., Population: Asymptomatic, nonpregnant adolescents and adults who have ever been sexually active and are at increased risk for syphilis infection., Evidence Assessment: Using a reaffirmation process, the USPSTF concludes with high certainty that there is a substantial net benefit of screening for syphilis infection in nonpregnant persons who are at increased risk for infection., Recommendation: The USPSTF recommends screening for syphilis infection in persons who are at increased risk for infection. (A recommendation).

Importance: The Centers for Disease Control and Prevention estimates that 210 000 children and adolescents younger than 20 years had diabetes as of 2018; of these, approximately 23 000 had type 2 diabetes. Youth with type 2 diabetes have an increased prevalence of associated chronic comorbid conditions, including hypertension, dyslipidemia, and nonalcoholic fatty liver disease. Data indicate that the incidence of type 2 diabetes is rising; from 2002-2003 to 2014-2015, incidence increased from 9.0 cases per 100 000 children and adolescents to 13.8 cases per 100 000 children and adolescents., Objective: The US Preventive Services Task Force (USPSTF) commissioned a review of the evidence on screening for prediabetes and type 2 diabetes in asymptomatic, nonpregnant persons younger than 18 years. This is a new recommendation., Population: Children and adolescents younger than 18 years without known diabetes or prediabetes or symptoms of diabetes or prediabetes., Evidence Assessment: The USPSTF concludes that the evidence is insufficient to assess the balance of benefits and harms of screening for type 2 diabetes in children and adolescents. There is a lack of evidence on the effect of screening for, and early detection and treatment of, type 2 diabetes on health outcomes in youth, and the balance of benefits and harms cannot be determined., Recommendation: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for type 2 diabetes in children and adolescents. (I statement).

Importance: Cardiovascular disease (CVD) is the leading cause of morbidity and death in the US and is the cause of more than 1 of every 4 deaths. Coronary heart disease is the single leading cause of death and accounts for 43% of deaths attributable to CVD in the US. In 2019, an estimated 558 000 deaths were caused by coronary heart disease and 109 000 deaths were caused by ischemic stroke., Objective: To update its 2016 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a review of the evidence on the benefits and harms of statins for reducing CVD-related morbidity or mortality or all-cause mortality., Population: Adults 40 years or older without a history of known CVD and who do not have signs and symptoms of CVD., Evidence Assessment: The USPSTF concludes with moderate certainty that statin use for the prevention of CVD events and all-cause mortality in adults aged 40 to 75 years with no history of CVD and who have 1 or more CVD risk factors (ie, dyslipidemia, diabetes, hypertension, or smoking) and an estimated 10-year CVD event risk of 10% or greater has at least a moderate net benefit. The USPSTF concludes with moderate certainty that statin use for the prevention of CVD events and all-cause mortality in adults aged 40 to 75 years with no history of CVD and who have 1 or more of these CVD risk factors and an estimated 10-year CVD event risk of 7.5% to less than 10% has at least a small net benefit. The USPSTF concludes that the evidence is insufficient to determine the balance of benefits and harms of statin use for the primary prevention of CVD events and mortality in adults 76 years or older with no history of CVD., Recommendation: The USPSTF recommends that clinicians prescribe a statin for the primary prevention of CVD for adults aged 40 to 75 years who have 1 or more CVD risk factors (ie, dyslipidemia, diabetes, hypertension, or smoking) and an estimated 10-year CVD risk of 10% or greater. (B recommendation) The USPSTF recommends that clinicians selectively offer a statin for the primary prevention of CVD for adults aged 40 to 75 years who have 1 or more of these CVD risk factors and an estimated 10-year CVD risk of 7.5% to less than 10%. The likelihood of benefit is smaller in this group than in persons with a 10-year risk of 10% or greater. (C recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of initiating a statin for the primary prevention of CVD events and mortality in adults 76 years or older. (I statement).

Importance: Cardiovascular disease (CVD), which includes heart disease, myocardial infarction, and stroke, is the leading cause of death in the US. A large proportion of CVD cases can be prevented by addressing modifiable risk factors, including smoking, obesity, diabetes, elevated blood pressure or hypertension, dyslipidemia, lack of physical activity, and unhealthy diet. Adults who adhere to national guidelines for a healthy diet and physical activity have lower rates of cardiovascular morbidity and mortality than those who do not; however, most US adults do not consume healthy diets or engage in physical activity at recommended levels., Objective: To update its 2017 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a review of the evidence on the benefits and harms of behavioral counseling interventions to promote healthy behaviors in adults without CVD risk factors., Population: Adults 18 years or older without known CVD risk factors, which include hypertension or elevated blood pressure, dyslipidemia, impaired fasting glucose or glucose tolerance, or mixed or multiple risk factors such as metabolic syndrome or an estimated 10-year CVD risk of 7.5% or greater., Evidence Assessment: The USPSTF concludes with moderate certainty that behavioral counseling interventions have a small net benefit on CVD risk in adults without CVD risk factors., Recommendation: The USPSTF recommends that clinicians individualize the decision to offer or refer adults without CVD risk factors to behavioral counseling interventions to promote a healthy diet and physical activity. (C recommendation).

Inhibitors of bromodomain and extraterminal domain (BET) proteins are possible anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prophylactics as they downregulate angiotensin-converting enzyme 2 (ACE2). Here we show that BET proteins should not be inactivated therapeutically because they are critical antiviral factors at the post-entry level. Depletion of BRD3 or BRD4 in cells overexpressing ACE2 exacerbates SARS-CoV-2 infection; the same is observed when cells with endogenous ACE2 expression are treated with BET inhibitors during infection and not before. Viral replication and mortality are also enhanced in BET inhibitor-treated mice overexpressing ACE2. BET inactivation suppresses interferon production induced by SARS-CoV-2, a process phenocopied by the envelope (E) protein previously identified as a possible "histone mimetic." E protein, in an acetylated form, directly binds the second bromodomain of BRD4. Our data support a model where SARS-CoV-2 E protein evolved to antagonize interferon responses via BET protein inhibition; this neutralization should not be further enhanced with BET inhibitor treatment., Competing Interests: Declaration of interests J.C.-S., J.O., and K.H. are employees and shareholders of Synthego Corporation., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: According to National Health and Nutrition Examination Survey data, 52% of surveyed US adults reported using at least 1 dietary supplement in the prior 30 days and 31% reported using a multivitamin-mineral supplement. The most commonly cited reason for using supplements is for overall health and wellness and to fill nutrient gaps in the diet. Cardiovascular disease and cancer are the 2 leading causes of death and combined account for approximately half of all deaths in the US annually. Inflammation and oxidative stress have been shown to have a role in both cardiovascular disease and cancer, and dietary supplements may have anti-inflammatory and antioxidative effects., Objective: To update its 2014 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a review of the evidence on the efficacy of supplementation with single nutrients, functionally related nutrient pairs, or multivitamins for reducing the risk of cardiovascular disease, cancer, and mortality in the general adult population, as well as the harms of supplementation., Population: Community-dwelling, nonpregnant adults., Evidence Assessment: The USPSTF concludes with moderate certainty that the harms of beta carotene supplementation outweigh the benefits for the prevention of cardiovascular disease or cancer. The USPSTF also concludes with moderate certainty that there is no net benefit of supplementation with vitamin E for the prevention of cardiovascular disease or cancer. The USPSTF concludes that the evidence is insufficient to determine the balance of benefits and harms of supplementation with multivitamins for the prevention of cardiovascular disease or cancer. Evidence is lacking and the balance of benefits and harms cannot be determined. The USPSTF concludes that the evidence is insufficient to determine the balance of benefits and harms of supplementation with single or paired nutrients (other than beta carotene and vitamin E) for the prevention of cardiovascular disease or cancer. Evidence is lacking and the balance of benefits and harms cannot be determined., Recommendation: The USPSTF recommends against the use of beta carotene or vitamin E supplements for the prevention of cardiovascular disease or cancer. (D recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the use of multivitamin supplements for the prevention of cardiovascular disease or cancer. (I statement) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the use of single- or paired-nutrient supplements (other than beta carotene and vitamin E) for the prevention of cardiovascular disease or cancer. (I statement).

Importance: Impairment of visual acuity is a serious public health problem in older adults. The number of persons 60 years or older with impaired visual acuity (defined as best corrected visual acuity worse than 20/40 but better than 20/200) was estimated at 2.91 million in 2015, and the number who are blind (defined as best corrected visual acuity of 20/200 or worse) was estimated at 760 000. Impaired visual acuity is consistently associated with decreased quality of life in older persons, including reduced ability to perform activities of daily living, work, and drive safely, as well as increased risk of falls and other unintentional injuries., Objective: To update its 2016 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the benefits and harms of screening for impaired visual acuity in older adults., Population: Asymptomatic adults 65 years or older who present in primary care without known impaired visual acuity and are not seeking care for vision problems., Evidence Assessment: The USPSTF concludes that the evidence is insufficient to assess the balance of benefits and harms of screening for impaired visual acuity in asymptomatic older adults. The evidence is lacking, and the balance of benefits and harms cannot be determined. More research is needed., Recommendation: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for impaired visual acuity in older adults. (I statement).

Importance: Glaucoma affects an estimated 2.7 million people in the US. It is the second-leading cause of irreversible blindness in the US and the leading cause of blindness in Black and Hispanic/Latino persons., Objective: To update its 2013 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the benefits and harms of screening for glaucoma in adults., Population: Adults 40 years or older who present in primary care and do not have signs or symptoms of open-angle glaucoma., Evidence Assessment: The USPSTF concludes that the evidence is insufficient to assess the balance of benefits and harms of screening for glaucoma in adults. The benefits and harms of screening for glaucoma in adults are uncertain. More research is needed., Recommendation: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for primary open-angle glaucoma in adults. (I statement).

Importance: Chronic obstructive pulmonary disease (COPD) is an irreversible reduction of airflow in the lungs. Progression to severe disease can prevent participation in normal activities because of deterioration of lung function. In 2020 it was estimated that approximately 6% of US adults had been diagnosed with COPD. Chronic lower respiratory disease, composed mainly of COPD, is the sixth leading cause of death in the US., Objective: To update its 2016 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a reaffirmation evidence update that focused on targeted key questions for benefits and harms of screening for COPD in asymptomatic adults and treatment in screen-detected or screen-relevant adults., Population: Asymptomatic adults who do not recognize or report respiratory symptoms., Evidence Assessment: Using a reaffirmation process, the USPSTF concludes with moderate certainty that screening for COPD in asymptomatic adults has no net benefit., Recommendation: The USPSTF recommends against screening for COPD in asymptomatic adults. (D recommendation).

Interferon restricts SARS-CoV-2 replication in cell culture, but only a handful of Interferon Stimulated Genes with antiviral activity against SARS-CoV-2 have been identified. Here, we describe a functional CRISPR/Cas9 screen aiming at identifying SARS-CoV-2 restriction factors. We identify DAXX, a scaffold protein residing in PML nuclear bodies known to limit the replication of DNA viruses and retroviruses, as a potent inhibitor of SARS-CoV-2 and SARS-CoV replication in human cells. Basal expression of DAXX is sufficient to limit the replication of SARS-CoV-2, and DAXX over-expression further restricts infection. DAXX restricts an early, post-entry step of the SARS-CoV-2 life cycle. DAXX-mediated restriction of SARS-CoV-2 is independent of the SUMOylation pathway but dependent on its D/E domain, also necessary for its protein-folding activity. SARS-CoV-2 infection triggers the re-localization of DAXX to cytoplasmic sites and promotes its degradation. Mechanistically, this process is mediated by the viral papain-like protease (PLpro) and the proteasome. Together, these results demonstrate that DAXX restricts SARS-CoV-2, which in turn has evolved a mechanism to counteract its action., (© 2022. The Author(s).)

Importance: Cardiovascular disease (CVD) is the leading cause of mortality in the US, accounting for more than 1 in 4 deaths. Each year, an estimated 605 000 people in the US have a first myocardial infarction and an estimated 610 000 experience a first stroke., Objective: To update its 2016 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review on the effectiveness of aspirin to reduce the risk of CVD events (myocardial infarction and stroke), cardiovascular mortality, and all-cause mortality in persons without a history of CVD. The systematic review also investigated the effect of aspirin use on colorectal cancer (CRC) incidence and mortality in primary CVD prevention populations, as well as the harms (particularly bleeding) associated with aspirin use. The USPSTF also commissioned a microsimulation modeling study to assess the net balance of benefits and harms from aspirin use for primary prevention of CVD and CRC, stratified by age, sex, and CVD risk level., Population: Adults 40 years or older without signs or symptoms of CVD or known CVD (including history of myocardial infarction or stroke) who are not at increased risk for bleeding (eg, no history of gastrointestinal ulcers, recent bleeding, other medical conditions, or use of medications that increase bleeding risk)., Evidence Assessment: The USPSTF concludes with moderate certainty that aspirin use for the primary prevention of CVD events in adults aged 40 to 59 years who have a 10% or greater 10-year CVD risk has a small net benefit. The USPSTF concludes with moderate certainty that initiating aspirin use for the primary prevention of CVD events in adults 60 years or older has no net benefit., Recommendation: The decision to initiate low-dose aspirin use for the primary prevention of CVD in adults aged 40 to 59 years who have a 10% or greater 10-year CVD risk should be an individual one. Evidence indicates that the net benefit of aspirin use in this group is small. Persons who are not at increased risk for bleeding and are willing to take low-dose aspirin daily are more likely to benefit. (C recommendation) The USPSTF recommends against initiating low-dose aspirin use for the primary prevention of CVD in adults 60 years or older. (D recommendation).

The US Preventive Services Task Force (USPSTF) works to improve the health of people nationwide by making evidence-based recommendations for preventive services. Patient-centered care is a core value in US health care. Shared decision-making (SDM), in which patients and clinicians make health decisions together, ensures patients' rights to be informed and involved in preventive care decisions and that these decisions are patient-centered. SDM has a role across the spectrum of USPSTF recommendations. For A or B recommendations (judged by the USPSTF to have high or moderate certainty of a moderate or substantial net benefit at the population level), SDM allows individual patients to decide whether to accept such services based on their personal values and preferences. For C recommendations (indicating at least moderate certainty of a small net benefit at the population level), SDM is critical for individual patients to decide whether the net benefit for them is worthwhile. For D recommendations (reflecting at least moderate certainty of a zero or negative net benefit) or I statements (low certainty of net benefit), clinicians should be prepared to discuss these services if patients ask. More evidence is needed to determine if, in addition to promoting patient-centeredness, SDM reduces inequities in preventive care, as well as to define new strategies to find time for discussion of preventive services in primary care.

Importance: Eating disorders (eg, binge eating disorder, bulimia nervosa, and anorexia nervosa) are a group of psychiatric conditions defined as a disturbance in eating or eating-related behaviors that impair physical or psychosocial functioning. According to large US cohort studies, estimated lifetime prevalences for anorexia nervosa, bulimia nervosa, and binge eating disorder in adult women are 1.42%, 0.46%, and 1.25%, respectively, and are lower in adult men (anorexia nervosa, 0.12%; bulimia nervosa, 0.08%; binge eating disorder, 0.42%). Eating disorder prevalence ranges from 0.3% to 2.3% in adolescent females and 0.3% to 1.3% in adolescent males. Eating disorders are associated with short-term and long-term adverse health outcomes, including physical, psychological, and social problems., Objective: The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the benefits and harms of screening for eating disorders in adolescents and adults with a normal or high body mass index. Evidence limited to populations who are underweight or have other physical signs or symptoms of eating disorders was not considered. The USPSTF has not previously made a recommendation on this topic., Population: Adolescents and adults (10 years or older) who have no signs or symptoms of eating disorders (eg, rapid weight loss, weight gain, or pronounced deviation from growth trajectory; pubertal delay; bradycardia; oligomenorrhea; and amenorrhea)., Evidence Assessment: The USPSTF concludes that the evidence is insufficient to assess the balance of benefits and harms of screening for eating disorders in adolescents and adults. The evidence is limited and the balance of benefits and harms cannot be determined., Recommendation: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for eating disorders in adolescents and adults. (I statement).

Importance: Atrial fibrillation (AF) is the most common cardiac arrhythmia. The prevalence of AF increases with age, from less than 0.2% in adults younger than 55 years to about 10% in those 85 years or older, with a higher prevalence in men than in women. It is uncertain whether the prevalence of AF differs by race and ethnicity. Atrial fibrillation is a major risk factor for ischemic stroke and is associated with a substantial increase in the risk of stroke. Approximately 20% of patients who have a stroke associated with AF are first diagnosed with AF at the time of the stroke or shortly thereafter., Objective: To update its 2018 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review on the benefits and harms of screening for AF in older adults, the accuracy of screening tests, the effectiveness of screening tests to detect previously undiagnosed AF compared with usual care, and the benefits and harms of anticoagulant therapy for the treatment of screen-detected AF in older adults., Population: Adults 50 years or older without a diagnosis or symptoms of AF and without a history of transient ischemic attack or stroke., Evidence Assessment: The USPSTF concludes that evidence is lacking, and the balance of benefits and harms of screening for AF in asymptomatic adults cannot be determined., Recommendation: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for AF. (I statement).

SARS-CoV-2 infection of human cells is initiated by the binding of the viral Spike protein to its cell-surface receptor ACE2. We conducted a targeted CRISPRi screen to uncover druggable pathways controlling Spike protein binding to human cells. Here we show that the protein BRD2 is required for ACE2 transcription in human lung epithelial cells and cardiomyocytes, and BRD2 inhibitors currently evaluated in clinical trials potently block endogenous ACE2 expression and SARS-CoV-2 infection of human cells, including those of human nasal epithelia. Moreover, pharmacological BRD2 inhibition with the drug ABBV-744 inhibited SARS-CoV-2 replication in Syrian hamsters. We also found that BRD2 controls transcription of several other genes induced upon SARS-CoV-2 infection, including the interferon response, which in turn regulates the antiviral response. Together, our results pinpoint BRD2 as a potent and essential regulator of the host response to SARS-CoV-2 infection and highlight the potential of BRD2 as a therapeutic target for COVID-19., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Importance: US life expectancy and health outcomes for preventable causes of disease have continued to lag in many populations that experience racism., Objective: To propose iterative changes to US Preventive Services Task Force (USPSTF) processes, methods, and recommendations and enact a commitment to eliminate health inequities for people affected by systemic racism., Design and Evidence: In February 2021, the USPSTF began operational steps in its work to create preventive care recommendations to address the harmful effects of racism. A commissioned methods report was conducted to inform this process. Key findings of the report informed proposed updates to the USPSTF methods to address populations adversely affected by systemic racism and proposed pilots on implementation of the proposed changes., Findings: The USPSTF proposes to consider the opportunity to reduce health inequities when selecting new preventive care topics and prioritizing current topics; seek evidence about the effects of systemic racism and health inequities in all research plans and public comments requested, and integrate available evidence into evidence reviews; and summarize the likely effects of systemic racism and health inequities on clinical preventive services in USPSTF recommendations. The USPSTF will elicit feedback from its partners and experts and proposed changes will be piloted on selected USPSTF topics., Conclusions and Relevance: The USPSTF has developed strategies intended to mitigate the influence of systemic racism in its recommendations. The USPSTF seeks to reduce health inequities and other effects of systemic racism through iterative changes in methods of developing evidence-based recommendations, with partner and public input in the activities to implement the advancements.

Importance: Dental caries is the most common chronic disease in children in the US. According to the 2011-2016 National Health and Nutrition Examination Survey, approximately 23% of children aged 2 to 5 years had dental caries in their primary teeth. Prevalence is higher in Mexican American children (33%) and non-Hispanic Black children (28%) than in non-Hispanic White children (18%). Dental caries in early childhood is associated with pain, loss of teeth, impaired growth, decreased weight gain, negative effects on quality of life, poor school performance, and future dental caries., Objective: To update its 2014 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review on screening and interventions to prevent dental caries in children younger than 5 years., Population: Asymptomatic children younger than 5 years., Evidence Assessment: The USPSTF concludes with moderate certainty that there is a moderate net benefit of preventing future dental caries with oral fluoride supplementation at recommended doses in children 6 months or older whose water supply is deficient in fluoride. The USPSTF concludes with moderate certainty that there is a moderate net benefit of preventing future dental caries with fluoride varnish application in all children younger than 5 years. The USPSTF concludes that the evidence is insufficient on performing routine oral screening examinations for dental caries by primary care clinicians in children younger than 5 years and that the balance of benefits and harms of screening cannot be determined., Recommendation: The USPSTF recommends that primary care clinicians prescribe oral fluoride supplementation starting at age 6 months for children whose water supply is deficient in fluoride. (B recommendation) The USPSTF recommends that primary care clinicians apply fluoride varnish to the primary teeth of all infants and children starting at the age of primary tooth eruption. (B recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of routine screening examinations for dental caries performed by primary care clinicians in children younger than 5 years. (I statement).

Importance: Preeclampsia is one of the most serious health problems that affect pregnant persons. It is a complication in approximately 4% of pregnancies in the US and contributes to both maternal and infant morbidity and mortality. Preeclampsia also accounts for 6% of preterm births and 19% of medically indicated preterm births in the US. There are racial and ethnic disparities in the prevalence of and mortality from preeclampsia. Non-Hispanic Black women are at greater risk for developing preeclampsia than other women and experience higher rates of maternal and infant morbidity and perinatal mortality., Objective: To update its 2014 recommendation, the USPSTF commissioned a systematic review to evaluate the effectiveness of low-dose aspirin use to prevent preeclampsia., Population: Pregnant persons at high risk for preeclampsia who have no prior adverse effects with or contraindications to low-dose aspirin., Evidence Assessment: The USPSTF concludes with moderate certainty that there is a substantial net benefit of daily low-dose aspirin use to reduce the risk for preeclampsia, preterm birth, small for gestational age/intrauterine growth restriction, and perinatal mortality in pregnant persons at high risk for preeclampsia., Recommendation: The USPSTF recommends the use of low-dose aspirin (81 mg/d) as preventive medication for preeclampsia after 12 weeks of gestation in persons who are at high risk for preeclampsia. (B recommendation).

Importance: Chlamydia and gonorrhea are among the most common sexually transmitted infections in the US. Infection rates are highest among adolescents and young adults of both sexes. Chlamydial and gonococcal infections in women are usually asymptomatic and may lead to pelvic inflammatory disease and its associated complications. Newborns of pregnant persons with untreated infection may develop neonatal chlamydial pneumonia or gonococcal or chlamydial ophthalmia. Infection in men may lead to urethritis and epididymitis. Both types of infection can increase risk of acquiring or transmitting HIV., Objective: To update its 2014 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the benefits and harms of screening for chlamydia and gonorrhea in sexually active adolescents and adults, including pregnant persons., Population: Asymptomatic, sexually active adolescents and adults, including pregnant persons., Evidence Assessment: The USPSTF concludes with moderate certainty that screening for chlamydia in all sexually active women 24 years or younger and in women 25 years or older who are at increased risk for infection has moderate net benefit. The USPSTF concludes with moderate certainty that screening for gonorrhea in all sexually active women 24 years or younger and in women 25 years or older who are at increased risk for infection has moderate net benefit. The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for chlamydia and gonorrhea in men., Recommendation: The USPSTF recommends screening for chlamydia in all sexually active women 24 years or younger and in women 25 years or older who are at increased risk for infection. (B recommendation) The USPSTF recommends screening for gonorrhea in all sexually active women 24 years or younger and in women 25 years or older who are at increased risk for infection. (B recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for chlamydia and gonorrhea in men. (I statement).

Importance: An estimated 13% of all US adults (18 years or older) have diabetes, and 34.5% meet criteria for prediabetes. The prevalences of prediabetes and diabetes are higher in older adults. Estimates of the risk of progression from prediabetes to diabetes vary widely, perhaps because of differences in the definition of prediabetes or the heterogeneity of prediabetes. Diabetes is the leading cause of kidney failure and new cases of blindness among adults in the US. It is also associated with increased risks of cardiovascular disease, nonalcoholic fatty liver disease, and nonalcoholic steatohepatitis and was estimated to be the seventh leading cause of death in the US in 2017. Screening asymptomatic adults for prediabetes and type 2 diabetes may allow earlier detection, diagnosis, and treatment, with the ultimate goal of improving health outcomes., Objective: To update its 2015 recommendation, the USPSTF commissioned a systematic review to evaluate screening for prediabetes and type 2 diabetes in asymptomatic, nonpregnant adults and preventive interventions for those with prediabetes., Population: Nonpregnant adults aged 35 to 70 years seen in primary care settings who have overweight or obesity (defined as a body mass index ≥25 and ≥30, respectively) and no symptoms of diabetes., Evidence Assessment: The USPSTF concludes with moderate certainty that screening for prediabetes and type 2 diabetes and offering or referring patients with prediabetes to effective preventive interventions has a moderate net benefit., Conclusions and Recommendation: The USPSTF recommends screening for prediabetes and type 2 diabetes in adults aged 35 to 70 years who have overweight or obesity. Clinicians should offer or refer patients with prediabetes to effective preventive interventions. (B recommendation).

Importance: Gestational diabetes is diabetes that develops during pregnancy. Prevalence of gestational diabetes in the US has been estimated at 5.8% to 9.2%, based on traditional diagnostic criteria, although it may be higher if more inclusive criteria are used. Pregnant persons with gestational diabetes are at increased risk for maternal and fetal complications, including preeclampsia, fetal macrosomia (which can cause shoulder dystocia and birth injury), and neonatal hypoglycemia. Gestational diabetes has also been associated with an increased risk of several long-term health outcomes in pregnant persons and intermediate outcomes in their offspring., Objective: The USPSTF commissioned a systematic review to evaluate the accuracy, benefits, and harms of screening for gestational diabetes and the benefits and harms of treatment for the pregnant person and infant., Population: Pregnant persons who have not been previously diagnosed with type 1 or type 2 diabetes., Evidence Assessment: The USPSTF concludes with moderate certainty that there is a moderate net benefit to screening for gestational diabetes at 24 weeks of gestation or after to improve maternal and fetal outcomes. The USPSTF concludes that the evidence on screening for gestational diabetes before 24 weeks of gestation is insufficient, and the balance of benefits and harms of screening cannot be determined., Recommendation: The USPSTF recommends screening for gestational diabetes in asymptomatic pregnant persons at 24 weeks of gestation or after. (B recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for gestational diabetes in asymptomatic pregnant persons before 24 weeks of gestation. (I statement).

Coronaviruses rely on host membranes for entry, establishment of replication centers, and egress. Compounds targeting cellular membrane biology and lipid biosynthetic pathways have previously shown promise as antivirals and are actively being pursued as treatments for other conditions. Here, we test small molecule inhibitors that target the PI3 kinase VPS34 or fatty acid metabolism for anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) activity. Our studies determine that compounds targeting VPS34 are potent SARS-CoV-2 inhibitors. Mechanistic studies with compounds targeting multiple steps up- and downstream of fatty acid synthase (FASN) identify the importance of triacylglycerol production and protein palmitoylation as requirements for efficient viral RNA synthesis and infectious virus production. Further, FASN knockout results in significantly impaired SARS-CoV-2 replication that can be rescued with fatty acid supplementation. Together, these studies clarify roles for VPS34 and fatty acid metabolism in SARS-CoV-2 replication and identify promising avenues for the development of countermeasures against SARS-CoV-2., Competing Interests: Declaration of Interests A.M.N. and S.A.C. are employees of Axion BioSystems who provided the Axion Maestro Z instrument used in these studies. C.F.B. serves on the scientific advisory board of Axion BioSystems. J.C.S., J.O., and K.H. are employees of Synthego Corporation who generated and provided the FASN knockout cells., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: The prevalence of overweight and obesity is increasing among persons of childbearing age and pregnant persons. In 2015, almost half of all persons began pregnancy with overweight (24%) or obesity (24%). Reported rates of overweight and obesity are higher among Black, Alaska Native/American Indian, and Hispanic women and lower among White and Asian women. Excess weight at the beginning of pregnancy and excess gestational weight gain have been associated with adverse maternal and infant health outcomes such as a large for gestational age infant, cesarean delivery, or preterm birth., Objective: The USPSTF commissioned a systematic review to evaluate the benefits and harms of behavioral counseling interventions to prevent adverse health outcomes associated with obesity during pregnancy and to evaluate intermediate outcomes, including excess gestational weight gain. This is a new recommendation., Population: Pregnant adolescents and adults in primary care settings., Evidence Assessment: The USPSTF concludes with moderate certainty that behavioral counseling interventions aimed at promoting healthy weight gain and preventing excess gestational weight gain in pregnancy have a moderate net benefit for pregnant persons., Recommendation: The USPSTF recommends that clinicians offer pregnant persons effective behavioral counseling interventions aimed at promoting healthy weight gain and preventing excess gestational weight gain in pregnancy. (B recommendation).

Importance: Colorectal cancer is the third leading cause of cancer death for both men and women, with an estimated 52 980 persons in the US projected to die of colorectal cancer in 2021. Colorectal cancer is most frequently diagnosed among persons aged 65 to 74 years. It is estimated that 10.5% of new colorectal cancer cases occur in persons younger than 50 years. Incidence of colorectal cancer (specifically adenocarcinoma) in adults aged 40 to 49 years has increased by almost 15% from 2000-2002 to 2014-2016. In 2016, 26% of eligible adults in the US had never been screened for colorectal cancer and in 2018, 31% were not up to date with screening., Objective: To update its 2016 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the benefits and harms of screening for colorectal cancer in adults 40 years or older. The review also examined whether these findings varied by age, sex, or race/ethnicity. In addition, as in 2016, the USPSTF commissioned a report from the Cancer Intervention and Surveillance Modeling Network Colorectal Cancer Working Group to provide information from comparative modeling on how estimated life-years gained, colorectal cancer cases averted, and colorectal cancer deaths averted vary by different starting and stopping ages for various screening strategies., Population: Asymptomatic adults 45 years or older at average risk of colorectal cancer (ie, no prior diagnosis of colorectal cancer, adenomatous polyps, or inflammatory bowel disease; no personal diagnosis or family history of known genetic disorders that predispose them to a high lifetime risk of colorectal cancer [such as Lynch syndrome or familial adenomatous polyposis])., Evidence Assessment: The USPSTF concludes with high certainty that screening for colorectal cancer in adults aged 50 to 75 years has substantial net benefit. The USPSTF concludes with moderate certainty that screening for colorectal cancer in adults aged 45 to 49 years has moderate net benefit. The USPSTF concludes with moderate certainty that screening for colorectal cancer in adults aged 76 to 85 years who have been previously screened has small net benefit. Adults who have never been screened for colorectal cancer are more likely to benefit., Recommendation: The USPSTF recommends screening for colorectal cancer in all adults aged 50 to 75 years. (A recommendation) The USPSTF recommends screening for colorectal cancer in adults aged 45 to 49 years. (B recommendation) The USPSTF recommends that clinicians selectively offer screening for colorectal cancer in adults aged 76 to 85 years. Evidence indicates that the net benefit of screening all persons in this age group is small. In determining whether this service is appropriate in individual cases, patients and clinicians should consider the patient's overall health, prior screening history, and preferences. (C recommendation).