Dual role of BdMUTE during stomatal development in the model grass Brachypodium distachyon.

Grasses form morphologically derived, four-celled stomata, where two dumbbell-shaped guard cells (GCs) are flanked by two lateral subsidiary cells (SCs). This innovative form enables rapid opening and closing kinetics and efficient plant-atmosphere gas exchange. The mobile bHLH transcription factor MUTE is required for SC formation in grasses. Yet whether and how MUTE also regulates GC development and whether MUTE mobility is required for SC recruitment is unclear. Here, we transgenically impaired BdMUTE mobility from GC to SC precursors in the emerging model grass Brachypodium distachyon. Our data indicate that reduced BdMUTE mobility severely affected the spatiotemporal coordination of GC and SC development. Furthermore, although BdMUTE has a cell-autonomous role in GC division orientation, complete dumbbell morphogenesis of GCs required SC recruitment. Finally, leaf-level gas exchange measurements showed that dosage-dependent complementation of the four-celled grass morphology was mirrored in a gradual physiological complementation of stomatal kinetics. Together, our work revealed a dual role of grass MUTE in regulating GC division orientation and SC recruitment, which in turn is required for GC morphogenesis and the rapid kinetics of grass stomata.

Best practices for the execution, analysis, and data storage of plant single-cell/nucleus transcriptomics.

Single-cell and single-nucleus RNA-sequencing technologies capture the expression of plant genes at an unprecedented resolution. Therefore, these technologies are gaining traction in plant molecular and developmental biology for elucidating the transcriptional changes across cell types in a specific tissue or organ, upon treatments, in response to biotic and abiotic stresses, or between genotypes. Despite the rapidly accelerating use of these technologies, collective and standardized experimental and analytical procedures to support the acquisition of high-quality data sets are still missing. In this commentary, we discuss common challenges associated with the use of single-cell transcriptomics in plants and propose general guidelines to improve reproducibility, quality, comparability, and interpretation and to make the data readily available to the community in this fast-developing field of research.

Nirsevimab: Expansion of Respiratory Syncytial Virus Prevention Options in Neonates, Infants, and At-Risk Young Children.

OBJECTIVE: Review available data from clinical trials of nirsevimab for efficacy and safety in the setting of respiratory syncytial virus (RSV) prophylaxis in infants and children, while exploring nirsevimab's role in clinical practice and highlighting continuing questions. DATA SOURCES: A literature search of PubMed was conducted utilizing the phrases "nirsevimab" and "medi8897." Additional references were identified through found references. Organizational guidelines, medication labeling, and regulatory organization presentations were utilized. STUDY SELECTION AND DATA EXTRACTION: Relevant clinical trials investigating nirsevimab in infants and children were included as well as other references on pharmacology, pharmacokinetics, and pharmacoeconomics. DATA SYNTHESIS: Nirsevimab, a once-a-season monoclonal antibody, demonstrated a 79.5% (95% CI, 65.9-87.7; P < 0.00001) lower incidence of RSV-associated medically attended lower respiratory tract infections (MA RSV-associated LRTI) and 77.3% (95% CI, 50.3-89.7; P = 0.0002) reduction in hospitalizations for RSV-associated MA-LRTI across 2 placebo-controlled studies. Nirsevimab demonstrated comparable safety to placebo with minor dermatologic reactions being the most common adverse event (0.9% vs 0.6%). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON WITH EXISTING AGENTS: Nirsevimab was approved by the US Food and Drug Administration, and recommended by the Advisory Committee on Immunization Practices and American Academy of Pediatrics for broad administration to infants entering their first RSV season and at risk patients during their second RSV season. Questions remain over efficacy in infants born < 29-week gestation and other economical considerations. CONCLUSIONS: Nirsevimab demonstrated clinical efficacy in reducing RSV-associated MA-LRTI and RSV-associated hospitalizations in infants and was well tolerated.

Co-occurrence of borderline and schizotypal personality disorders: a scoping review.

BACKGROUND: The historical concept of borderline conditions refers to the pathology on the border between neurosis and psychosis. In DSM-III the conditions were divided into specific but also somewhat overlapping diagnostic criteria for Borderline Personality Disorder (BPD) and Schizotypal Personality Disorder (SPD). This phenomenological overlap, which results in co-occurrence of the two diagnoses, remains a clinical challenge to this day. METHODS: To address this issue we examined the co-occurrence of SPD and BPD according to the established DSM-IV/-5 diagnostic criteria. A literature search was conducted including studies that employed a structured interview with defined BPD and SPD criteria. RESULTS: Studies from 20 samples were included (i.e. 15 patients, 3 community and 2 forensic samples). For patients diagnosed primarily with BPD, 1-27% also met the criteria for SPD and for patients diagnosed primarily with SPD, 5 - 33% showed co-occurrence with BPD. In the forensic samples, co-occurrence for primary BPD was 10% and 67 - 82% for primary SPD. In the community samples, co-occurrence for primary BPD was 29% and 50% for primary SPD. The pattern of co-occurrence across community samples was particularly heterogeneous. CONCLUSION: The identified co-occurrences for BPD and SPD were considerably sample-dependent, and samples and measurements were generally too heterogeneous for a precise meta-analysis. Forensic and community samples generally showed higher co-occurrences, but these findings were characterized by potential methodological limitations.

Influence of ceramic thickness and dental substrate on the survival rate and failure load of non-retentive occlusal veneers after fatigue.

OBJECTIVE: To investigate the effect of ceramic thickness and dental substrate (enamel vs. dentin/enamel) on the survival rate and failure load of non-retentive occlusal veneers. MATERIALS AND METHODS: Human maxillary molars (n = 60) were divided into five test-groups (n = 12). The groups (named DE-1.5, DE-1.0, DE-0.5, E-1.0, E-0.5) differed in their dental substrate (E = enamel, DE = dentin/enamel) and restoration thickness (standard: 1.5 mm, thin: 1.0 mm, ultrathin: 0.5 mm). All teeth were prepared for non-retentive monolithic lithium-disilicate occlusal veneers (IPS e.max Press, Ivoclar). Restorations were adhesively cemented (Syntac Classic/Variolink II, Ivoclar) and exposed to thermomechanical fatigue (1.2 million cycles, 1.6 Hz, 49 N/ 5-55°C). Single load to failure was performed using a universal testing-machine. A linear-regression model was applied, pairwise comparisons used the Student-Newman-Keuls method (p < 0.05). RESULTS: Three dentin-based occlusal veneers (one DE-1.0, two DE-0.5) revealed cracks after fatigue exposure, which corresponds to an overall-survival rate of 95%. Load to failure resulted in the following ranking: 2142 N(DE-0.5) > 2105 N(E-1.0) > 2075 N(E-0.5) > 1440 N(DE-1.5) > 1430 N(DE-1.0). Thin (E-1.0) and ultrathin enamel-based occlusal veneers (E-0.5) revealed high failure loads and surpassed the standard thickness dentin-based veneers (DE-1.5) significantly (p = 0.044, p = 0.022). CONCLUSION: All tested monolithic lithium disilicate occlusal veneers obtained failure loads above physiological chewing forces. Thin and ultrathin enamel-based occlusal veneers outperformed the standard thick dentin-based occlusal veneers. CLINICAL SIGNIFICANCE: Minimally invasive enamel-based occlusal veneer restorations with non-retentive preparation design may serve as a conservative treatment option.

Burden of infectious disease studies in Europe and the United Kingdom: a review of methodological design choices.

This systematic literature review aimed to provide an overview of the characteristics and methods used in studies applying the disability-adjusted life years (DALY) concept for infectious diseases within European Union (EU)/European Economic Area (EEA)/European Free Trade Association (EFTA) countries and the United Kingdom. Electronic databases and grey literature were searched for articles reporting the assessment of DALY and its components. We considered studies in which researchers performed DALY calculations using primary epidemiological data input sources. We screened 3053 studies of which 2948 were excluded and 105 studies met our inclusion criteria. Of these studies, 22 were multi-country and 83 were single-country studies, of which 46 were from the Netherlands. Food- and water-borne diseases were the most frequently studied infectious diseases. Between 2015 and 2022, the number of burden of infectious disease studies was 1.6 times higher compared to that published between 2000 and 2014. Almost all studies (97%) estimated DALYs based on the incidence- and pathogen-based approach and without social weighting functions; however, there was less methodological consensus with regards to the disability weights and life tables that were applied. The number of burden of infectious disease studies undertaken across Europe has increased over time. Development and use of guidelines will promote performing burden of infectious disease studies and facilitate comparability of the results.

A Review of the Data Supporting Use of COVID-19 Vaccinations in the Pediatric Population.

OBJECTIVE: The objective of this study was to review the effectiveness and safety of COVID-19 vaccinations in the pediatric population. DATA SOURCES: PubMed/Medline (September 2020 to December 2022), the Centers for Disease Control and Prevention, and Food and Drug Administration (FDA) websites. STUDY SELECTION AND DATA EXTRACTION: Publications regarding the safety and efficacy of COVID-19 vaccinations in children were included. DATA SYNTHESIS: Vaccines authorized for use in children include two monovalent mRNA vaccines (≥6 months old) and one monovalent protein subunit adjuvant vaccine (adolescents only). Omicron-specific mRNA bivalent boosters are authorized for children ≥6 months old. Studies after monovalent vaccine authorization illustrated efficacy in children >5 to 6 years of age, specifically decreased severe COVID-19 (including mortality) and multisystem inflammatory response syndrome occurrence (including during Omicron predominance). Available data for children <5 to 6 years suggests efficacy, although data are limited. Monovalent vaccine efficacy against Omicron infections may wane as early as 2 months, but protection against severe disease complications may last longer, and bivalent Omicron boosters are anticipated to increase effectiveness. Myocarditis/pericarditis is a safety concern associated with the COVID-19 vaccinations but occurs less frequently then COVID-19 complications and thus the benefit outweighs the risks. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Caregivers seek information from health care professionals regarding vaccine safety and efficacy. Pharmacists can use the objective information in this review to educate caregivers and effectively administer COVID-19 vaccines to patients. CONCLUSIONS: There is sufficient and continually growing safety and efficacy data available to recommend COVID-19 vaccinations for children ≥6 months of age.

Considerations for Treating Nonobstetric Diseases in Pregnant Patients in the Emergency Department Setting.

OBJECTIVE: To provide nonobstetric practitioners with an overview of key concepts for the pregnant patient and review treatment of 3 common acute nonobstetric diseases encountered in the emergency department setting. DATA SOURCES: A literature search of PubMed was performed (1997-February 2023) using key search terms related to pregnancy, pain, urinary tract infection (UTI), venous thromboembolism (VTE), and anticoagulants. STUDY SELECTION AND DATA EXTRACTION: Relevant articles in English and humans were considered. DATA SYNTHESIS: When caring for a pregnant patient, it is important to utilize appropriate assessments, understand terms used in this population, and recognize how the physiological and pharmacokinetic changes that occur in pregnancy can influence medication use. Pain, UTIs, and VTE are common in this population. Acetaminophen is the most widely used medication for the management of pain during pregnancy and the drug of choice for mild pain in pregnancy not responsive to nonpharmacologic treatment. Pyelonephritis is the most common nonobstetric cause of hospitalization for pregnant patients. Antimicrobial treatment should consider maternal-fetal safety and local resistance patterns. Pregnant and postpartum patients have a 4- to 5-fold increased risk of developing a VTE compared with nonpregnant patients. Low-molecular-weight heparin is the preferred treatment. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Pregnant patients often seek acute care in the emergency department setting for nonobstetric needs. Pharmacists in this setting should understand appropriate assessment questions and terms used within this population, the basics of physiological and pharmacokinetic changes in pregnancy that can impact treatment, and which resources are best to utilize for drug information of the pregnant patient. CONCLUSION: Practitioners in the acute care setting commonly encounter pregnant patients seeking care for nonobstetric concerns. This article covers key pregnancy-related information for the nonobstetric practitioner and focuses on the management of acute pain, UTI, and VTE during pregnancy.

Call to expand access to vaccines for children through pharmacist education, collaboration, and advocacy.

Vaccines are a daycare and school requirement for children. The Public Readiness and Emergency Preparedness (PREP) Act 3rd amendment grants pharmacists and pharmacy interns the capability to vaccinate children at ages 3-18 years according to the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices schedule of recommended vaccines. Before this, only some state boards of pharmacy allowed pharmacists to administer pediatric vaccines. Despite these opportunities, immunization training programs lack the comprehensive training of pediatric vaccines and administration for pharmacists and pharmacy interns without additional financial cost. All pharmacists should be adequately trained and pharmacies be reimbursed to provide vaccines to all ages of pediatric patients. Advocacy is necessary to ensure children have reliable, affordable, and convenient access to lifesaving vaccines today and after the PREP Act expires.

Trusting information systems in everyday work events - effects on cognitive resources, performance, and well-being.

In today's data-intensive work environments, information systems are crucial for supporting workers. However, workers often do not rely on these systems but resort to workarounds. We argue that trust is essential for workers' reliance on information systems, positively affecting workers' cognitive resources, performance, and well-being. Moreover, we argue that the organisational context (accountability, distractions) and user-related factors qualify trust-outcome associations by affecting workers' trust calibration. In a preregistered study, we asked N = 291 employed users of information systems to re-experience prior everyday usage events (event reconstruction method) and assess event-specific trust in the system, work outcomes, and context conditions. Results confirmed the assumed association between trust in the information system and workers' ratings of both performance and well-being. Moreover, workers' technology competence and need for cognition - but not contextual conditions - qualified trust-outcome associations. Our results offer specific suggestions for achieving successful use of information systems at work.

This preregistered study with 291 employees demonstrates the importance of trust in information systems for workers' performance and well-being in everyday work events. User-related factors, namely, users' technology competence and need for cognition, further qualified these effects. Practical implications for active trust management are drawn.

Long-term effects of COVID-19 on work routines and organizational culture - A case study within higher education's administration.

As a sudden, external event, the COVID-19 pandemic rapidly disrupted the workplace and required organizations to digitalize their working approaches. To understand how such external events affect organizations in the short- and long-term, we investigated the case of a higher education institution's administration, which combines features of public and private organizations. We applied a longitudinal case study and conducted interviews with 39 German higher education institution (HEI) employees at two time points during the first (2020) and second (2021) lockdown. Content analyses revealed that a general openness toward change and distinct technical infrastructure enabled efficient coping with the pandemic despite struggles with digitalization and rigidity. Advantages in work outcomes were contrasted with losses in social interactions. Flexible models (e.g., working from home or the office) were desirable long-term work concepts. We integrated our findings in a framework on factors that contribute to supporting organizational adaptations and derived practical recommendations.

Lack of N-glycosylation increases amyloidogenic processing of the amyloid precursor protein.

The amyloid precursor protein (APP) is a ubiquitously expressed type 1 transmembrane protein mostly known for serving as a precursor to the amyloid-ß peptide (Aß), a culprit in Alzheimer disease (AD). However, APP also has important physiological functions by being implicated in, for instance, adhesion, signaling, neuronal development, and synaptic function. Human APP contains 2 N-glycosylation sites, at asparagine (N) 467 (N467) and N496. Here, we studied the role of N-glycosylation on APP trafficking and processing by constructing APP-SNAP plasmid vectors for wildtype APP and N-glycosylation site mutants in which N467 or N496 was replaced by glutamine (Q) and expressed these in HEK293T cells. Lack of either of the 2 N-glycans resulted in a reduction in the size of intracellular APP-SNAP-positive vesicles and a reduction of APP-SNAP in the plasma membrane and lysosomes. Importantly, loss of either of the 2 N-glycans resulted in elevated levels of intracellular as well as secreted Aß42. These data suggest that N-glycans have a major impact on trafficking and processing of APP and could play an important role in the development of AD.

Disability adjusted life years associated with COVID-19 in Denmark in the first year of the pandemic.

BACKGROUND: Burden of disease studies measure the public health impact of a disease in a society. The aim of this study was to quantify the direct burden of COVID-19 in the first 12 months of the epidemic in Denmark. METHODS: We collected national surveillance data on positive individuals for SARS-CoV-2 with RT-PCR, hospitalization data, and COVID-19 mortality reported in the period between 26th of February, 2020 to 25th of February, 2021. We calculated disability adjusted life years (DALYs) based on the European Burden of Disease Network consensus COVID-19 model, which considers mild, severe, critical health states, and premature death. We conducted sensitivity analyses for two different death-registration scenarios, within 30 and 60 days after first positive test, respectively. RESULTS: We estimated that of the 211,823 individuals who tested positive to SARS-CoV-2 by RT-PCR in the one-year period, 124,163 (59%; 95% uncertainty interval (UI) 112,782-133,857) had at least mild symptoms of disease. The total estimated disease burden was 30,180 DALYs (95% UI 30,126; 30,242), corresponding to 520 DALYs/100,000. The disease burden was higher in the age groups above 70 years of age, particularly in men. Years of life lost (YLL) contributed with more than 99% of total DALYs. The results of the scenario analysis showed that defining COVID-19-related fatalities as deaths registered up to 30 days after the first positive test led to a lower YLL estimate than when using a 60-days window. CONCLUSION: COVID-19 led to a substantial public health impact in Denmark in the first full year of the epidemic. Our estimates suggest that it was the the sixth most frequent cause of YLL in Denmark in 2020. This impact will be higher when including the post-acute consequences of COVID-19 and indirect health outcomes.

Methodological considerations in injury burden of disease studies across Europe: a systematic literature review.

BACKGROUND: Calculating the disease burden due to injury is complex, as it requires many methodological choices. Until now, an overview of the methodological design choices that have been made in burden of disease (BoD) studies in injury populations is not available. The aim of this systematic literature review was to identify existing injury BoD studies undertaken across Europe and to comprehensively review the methodological design choices and assumption parameters that have been made to calculate years of life lost (YLL) and years lived with disability (YLD) in these studies. METHODS: We searched EMBASE, MEDLINE, Cochrane Central, Google Scholar, and Web of Science, and the grey literature supplemented by handsearching, for BoD studies. We included injury BoD studies that quantified the BoD expressed in YLL, YLD, and disability-adjusted life years (DALY) in countries within the European Region between early-1990 and mid-2021. RESULTS: We retrieved 2,914 results of which 48 performed an injury-specific BoD assessment. Single-country independent and Global Burden of Disease (GBD)-linked injury BoD studies were performed in 11 European countries. Approximately 79% of injury BoD studies reported the BoD by external cause-of-injury. Most independent studies used the incidence-based approach to calculate YLDs. About half of the injury disease burden studies applied disability weights (DWs) developed by the GBD study. Almost all independent injury studies have determined YLL using national life tables. CONCLUSIONS: Considerable methodological variation across independent injury BoD assessments was observed; differences were mainly apparent in the design choices and assumption parameters towards injury YLD calculations, implementation of DWs, and the choice of life table for YLL calculations. Development and use of guidelines for performing and reporting of injury BoD studies is crucial to enhance transparency and comparability of injury BoD estimates across Europe and beyond.

Engineered Human Induced Pluripotent Cells Enable Genetic Code Expansion in Brain Organoids.

Human induced pluripotent stem cell (hiPSC) technology has revolutionized studies on human biology. A wide range of cell types and tissue models can be derived from hiPSCs to study complex human diseases. Here, we use PiggyBac-mediated transgenesis to engineer hiPSCs with an expanded genetic code. We demonstrate that genomic integration of expression cassettes for a pyrrolysyl-tRNA synthetase (PylRS), pyrrolysyl-tRNA (PylT) and the target protein of interest enables site-specific incorporation of a non-canonical amino acid (ncAA) in response to an amber stop codon. Neural stem cells, neurons and brain organoids derived from the engineered hiPSCs continue to express the amber suppression machinery and produce ncAA-bearing reporter. The incorporated ncAA can serve as a minimal bioorthogonal handle for further modifications by labeling with fluorescent dyes. Site-directed ncAA mutagenesis will open a wide range of applications to probe and manipulate proteins in brain organoids and other hiPSC-derived cell types and complex tissue models.

MEIS2 sequence variant in a child with intellectual disability and cardiac defects: Expansion of the phenotypic spectrum and documentation of low-level mosaicism in an unaffected parent.

Deletions and pathogenic sequence variants in Myeloid Ecotropic Insertion Site 2 (MEIS2) gene have been reported to cause a recognizable triad of intellectual disability, congenital heart malformations, and palatal defects. To date, 18 individuals with de novo pathogenic sequence variants in MEIS2 have been reported in the literature, most with all three cardinal features. We recently saw a young boy, almost 3 years of age, who was known to have mosaic XYY syndrome (47,XYY [23]/46,XY[7]). He presented with atrial and ventricular septal defects, developmental delay, facial dysmorphism, gastroesophageal reflux, undescended testicle, a buried penis with penoscrotal transposition, primary neutropenia, and a branchial cleft sinus. Whole-exome sequencing identified a previously reported in-frame pathogenic deletion (c.998_1000delGAA; p.R333del; NM_170674.4) in MEIS2. His unaffected father was confirmed to have low-level mosaicism for the same MEIS2 variant. The proband represents the 19th reported individual with a pathogenic sequence variant in MEIS2 and expands the phenotypic spectrum to include primary neutropenia, branchial anomalies, and complex genital anomalies. Furthermore, to our knowledge this is the first reported case of mosaicism for a variant in this gene in an apparently unaffected parent. This finding would have implications for recurrence risk counseling for families.

The Influence of the Food and Drug Administration Pregnancy and Lactation Labeling Rule on Drug Information Resources.

BACKGROUND: Drug information resources are commonly used by health-care providers answering pregnancy-related medication questions. In 2015, the United States Food and Drug Administration approved a new pregnancy and lactation medication labeling content and format, removing the pregnancy category, and using a narrative. Despite labeling requirements changing, it is unknown if drug information resources updated monographs to reflect these changes. OBJECTIVE: The primary objective was to evaluate if commonly used drug information resources provide pregnancy information listed similar to the requirements of the Pregnancy and Lactation Labeling Rule (PLLR). Secondary analyses included evaluating the references and inclusion of the pregnancy category rating. METHODS: Pregnancy recommendations for 23 medications were evaluated in 9 drug information resources (Clinical Pharmacology, Drugs in Pregnancy and Lactation, Epocrates®, First Databank, LexiComp® Online, LexiComp® Online Pregnancy & Lactation, In-Depth, Medi-Span®, Micromedex®, and Multum®). The number of references per drug monograph and most recent reference publication year was obtained. RESULTS: LexiComp® Online Pregnancy & Lactation, In-Depth mimics the new PLLR structure and consistently had the highest number of and most recent references when the medication was included. Drugs in Pregnancy and Lactation was the next most similar in content with the PLLR and second in most references per monograph; however, the most recent reference was the textbook publication year. CONCLUSION AND RELEVANCE: LexiComp® Online Pregnancy & Lactation, In-Depth and Drugs in Pregnancy and Lactation provided pregnancy information in a format most similar to the PLLR. However, several drug information resources contained pregnancy categories ratings that were to be removed from medication labeling per the PLLR.

Exploring Identity Disturbance and Psychotic Spectrum Symptoms as Predictors of Borderline and Schizotypal Personality Disorders.

INTRODUCTION: Borderline personality disorder (BPD) and schizotypal personality disorder (SPD) were introduced in DSM-III and retained in DSM-5 Section II. They often co-occur and some aspects of the clinical differentiation between the 2 diagnoses remain unclear (e.g., psychotic-like features and identity disturbance). METHODS: The present study explored if self-reported identity disturbance and psychosis proneness could discriminate between the BPD and SPD DSM-5 diagnoses. All patients were interviewed with the Schedules for Clinical Assessment in Neuropsychiatry and the Structured Clinical Interview for DSM-5 Personality Disorders, and administered the Inventory of Personality Organization, Self-Concept and Identity Measure, Schizotypal Personality Questionnaire, Perceptual Aberration Scale, and the Magical Ideation Scale. RESULTS: A total of 105 patients were initially assessed, 26 were excluded, and the final sample (N = 79) was composed of 34 BPD patients, 25 SPD patients, and 20 patients with co-occurring SPD and BPD. The BPD group (n = 34) was first compared with the pure SPD group (n = 25), and secondly with the total group of patients diagnosed with SPD (n = 25 + 20). Logistic regression analyses indicated that primitive defenses and disorganization best differentiated the BPD and the pure SPD group, while primitive defenses and interpersonal factor along with perceptual aberrations best differentiated the BPD and the total SPD group. CONCLUSION: Identity disturbance did not predict the diagnostic groups, but BPD patients were characterized by primitive defenses, which are closely related to identity disturbance. Pure SPD was characterized by oddness/eccentricity, while the lack of specificity for cognitive-perceptual symptoms suggests that the positive symptoms do not differentiate BPD from SPD.

Doxycycline and Tooth Discoloration in Children: Changing of Recommendations Based on Evidence of Safety.

Doxycycline use has historically been limited to children older than 8 years because of concerns regarding permanent tooth discoloration. Six studies assessed tooth discoloration in at least 338 patients exposed to doxycycline before 8 years of age. Six patients had potential discoloration, but studies consistently found no difference in tooth discoloration between exposed patients and controls. Recommendations have changed stating doxycycline, but not other tetracyclines, can be used for short courses (<21 days) regardless of age. Clinicians should be aware of these data because doxycycline use may extend to disease states apart from tick-borne illnesses in pediatric patients.

Common Bacterial and Viral Infections: Review of Management in the Pregnant Patient.

OBJECTIVE: To review the treatment of common bacterial and viral infections occurring in the pregnant patient. DATA SOURCES: A literature search of MEDLINE was performed (inception to October 2018). The Centers for Disease Control and Prevention website was utilized for additional information. STUDY SELECTION AND DATA EXTRACTION: Relevant English-language studies and those conducted in humans were considered. DATA SYNTHESIS: ß-Lactams alone or in combination are the preferred treatment for many common infections in pregnancy, such as urinary tract infections, pelvic inflammatory disease (PID), gonococcal infections, syphilis, chancroid, upper- and lower-respiratory-tract infections, certain gastrointestinal infections, Group B Streptococcus, listeriosis, and intrauterine inflammation or infection. Macrolides, particularly azithromycin, are also utilized for the treatment of PID, chlamydia, gonococcal infections, chancroid, community-acquired pneumonia, and certain gastrointestinal infections. Other antibiotics or antivirals such as vancomycin, aminoglycosides, metronidazole, nitrofurantoin, fosfomycin, acyclovir, valacyclovir, and oseltamivir are included in the preferred therapy for some common bacterial and viral infections in pregnant patients as well. Relevance to Patient Care and Clinical Practice: This review synthesizes available evidence of treatments of common infections in pregnancy and provides a concise summary to guide clinicians on empirical treatment during pregnancy. CONCLUSIONS: There are limited data on clinical outcomes in pregnant patients with common bacterial and viral infections. Empirical management decisions require balance of benefit and risk to both mother and infant. Although few clinical practice guidelines have quality evidence for strong recommendations in this population, clinicians should weigh antimicrobial dosing, pharmacokinetics, safety, and established effectiveness to optimize antimicrobial therapy in pregnancy.