The ciliary protein C2cd3 is required for mandibular musculoskeletal tissue patterning.

The mandible is composed of several musculoskeletal tissues including bone, cartilage, and tendon that require precise patterning to ensure structural and functional integrity. Interestingly, most of these tissues are derived from one multipotent cell population called cranial neural crest cells (CNCCs). How CNCCs are properly instructed to differentiate into various tissue types remains nebulous. To better understand the mechanisms necessary for the patterning of mandibular musculoskeletal tissues we utilized the avian mutant talpid2 (ta2) which presents with several malformations of the facial skeleton including dysplastic tendons, mispatterned musculature, and bilateral ectopic cartilaginous processes extending off Meckel's cartilage. We found an ectopic epithelial BMP signaling domain in the ta2 mandibular prominence (MNP) that correlated with the subsequent expansion of SOX9+ cartilage precursors. These findings were validated with conditional murine models suggesting an evolutionarily conserved mechanism for CNCC-derived musculoskeletal patterning. Collectively, these data support a model in which cilia are required to define epithelial signal centers essential for proper musculoskeletal patterning of CNCC-derived mesenchyme.

Ciliopathic micrognathia is caused by aberrant skeletal differentiation and remodeling.

Ciliopathies represent a growing class of diseases caused by defects in microtubule-based organelles called primary cilia. Approximately 30% of ciliopathies are characterized by craniofacial phenotypes such as craniosynostosis, cleft lip/palate and micrognathia. Patients with ciliopathic micrognathia experience a particular set of difficulties, including impaired feeding and breathing, and have extremely limited treatment options. To understand the cellular and molecular basis for ciliopathic micrognathia, we used the talpid2 (ta2 ), a bona fide avian model for the human ciliopathy oral-facial-digital syndrome subtype 14. Histological analyses revealed that the onset of ciliopathic micrognathia in ta2 embryos occurred at the earliest stages of mandibular development. Neural crest-derived skeletal progenitor cells were particularly sensitive to a ciliopathic insult, undergoing unchecked passage through the cell cycle and subsequent increased proliferation. Furthermore, whereas neural crest-derived skeletal differentiation was initiated, osteoblast maturation failed to progress to completion. Additional molecular analyses revealed that an imbalance in the ratio of bone deposition and resorption also contributed to ciliopathic micrognathia in ta2 embryos. Thus, our results suggest that ciliopathic micrognathia is a consequence of multiple aberrant cellular processes necessary for skeletal development, and provide potential avenues for future therapeutic treatments.

Postoperative urinary retention by void trial methodology following radical hysterectomy for cervical cancer.

OBJECTIVES: Radical hysterectomy is the standard of care for management of early-stage cervical cancer and is associated with postoperative urinary retention. No clear consensus exists regarding optimal voiding trial methodology for mitigating postoperative urinary retention. Our objective was to evaluate the association between type of postoperative voiding trial and risk of urinary retention after radical hysterectomy for cervical cancer. METHODS: We conducted a retrospective analysis of patients undergoing radical hysterectomy for apparent early-stage cervical cancer (FIGO 2018 Stage IA2-IB2) between January 2014 and February 2023. We compared incidence of urinary retention and perioperative outcomes based on method of postoperative voiding trial (timed, autofill, or backfill). Multivariate logistic regression was used to determine association of type of void trial with absence of urinary retention within 30 days postoperatively. RESULTS: Of the 115 patients identified, 48 (41.8%) patients completed a timed void trial, 40 (34.7%) an autofill void trial, and 27 (23.5%) a backfill void trial. 44.3% of patients developed postoperative urinary retention with no differences based on void trial (p = 0.17). Urinary retention was more likely to resolve by 7 (p = 0.012) and 30 days (p = 0.01) for patients undergoing backfill voiding trials, compared to other trials. In multivariate models, backfill void trial was associated with absence of 30-day urinary retention, compared to other trials (aOR 15.1; 95% C.I. 1.5-154.9). CONCLUSIONS: Rates of urinary retention following radical hysterectomy do not differ based on postoperative void trial methodology. A backfill void trial following radical hysterectomy may lead to increased rates of resolution of postoperative urinary retention.

Patient reported improvement in sexual health outcomes following care in a sexual health clinic for women with cancer.

PURPOSE: Sexual health concerns are common among female cancer survivors. Few data exist regarding patient-reported outcomes following interventions in this population. We aimed to determine patient-reported adherence and impact of interventions provided in an academic specialty clinic for treatment of sexual health problems. METHODS: A cross-sectional quality improvement survey regarding sexual problems, adherence with recommended therapies, and improvement following intervention was administered to all women seen at the Women's Integrative Sexual Health (WISH) program at the University of Wisconsin-Madison between November 2013 and July 2019. Descriptive and Kruskal-Wallis tests were used to explore differences between groups. RESULTS: Two hundred twenty women (median age at first visit = 50 years, 53.1% breast cancer) were identified; N =113 surveys were completed (response rate = 49.6%). The most common presenting complaints were pain with intercourse (87.2%), vaginal dryness (85.3%), and low libido (82.6%). Menopausal women were more likely than premenopausal women to present with vaginal dryness (93.4% vs. 69.7%, p = .001) and pain with intercourse (93.4% vs. 76.5%, p = .02). Nearly all women adhered to recommendations for vaginal moisturizers/lubricants (96.9-100%) and vibrating vaginal wands (82.4-92.3%). A majority found recommended interventions helpful regardless of menopausal status or cancer type and reported persistent improvement. Nearly all women had improvement in understanding sexual health (92%) and would recommend the WISH program to others (91%). CONCLUSION: Women with cancer report integrative sexual health care to address sexual problems that are helpful and result in long-term improvement. Patients are overall highly adherent to recommended therapies, and nearly all would recommend the program to others. IMPLICATIONS FOR CANCER SURVIVORS: Dedicated care to address sexual health in women after cancer treatment improves patient-reported sexual health outcomes across all cancer types.

Multiphasic exercise prehabilitation for patients undergoing surgery for head and neck cancer: a hybrid effectiveness-implementation study protocol.

Head and neck cancer (HNC) treatment often consists of major surgery followed by adjuvant therapy, which can result in treatment-related side effects, decreased physical function, and diminished quality of life. Perioperative nutrition interventions and early mobilization improve recovery after HNC treatment. However, there are few studies on prehabilitation that include exercise within the HNC surgical care pathway. We have designed a multiphasic exercise prehabilitation intervention for HNC patients undergoing surgical resection with free flap reconstruction. We will use a hybrid effectiveness-implementation study design guided by the RE-AIM framework to address the following objectives: (1) to evaluate intervention benefits through physical function and patient-reported outcome assessments; (2) to determine the safety and feasibility of the prehabilitation intervention; (3) to evaluate the implementation of exercise within the HNC surgical care pathway; and (4) to establish a post-operative screening and referral pathway to exercise oncology resources. The results of this study will provide evidence for the benefits and costs of a multiphasic exercise prehabilitation intervention embedded within the HNC surgical care pathway. This paper describes the study protocol design, multiphasic exercise prehabilitation intervention, planned analyses, and dissemination of findings. Trial registration: https://clinicaltrials.gov/NCT04598087.

Splenectomy at the time of primary or interval cytoreductive surgery for epithelial ovarian carcinoma: A review of outcomes.

OBJECTIVES: We describe post-operative complications after cytoreductive surgery with and without splenectomy for Stage III or IV epithelial ovarian cancer, and identify areas for quality improvement in post-splenectomy care. METHODS: All patients with ovarian cancer cytoreductive surgery from 2008 to 2018 were identified using an institutional database Gynecologic Oncology Longitudinal Data Collection and Utilization Program (GOLD CUP). We compared patients who had and did not have splenectomy as part of cytoreductive surgery by demographics, comorbidities, stage, operative and post-operative data, readmission rates, progression free survival, overall survival and death from disease. Quality metrics reported include receipt of post-splenectomy education handouts and encapsulated-organism vaccines. Statistical analysis was completed in STATA SE 16.0. RESULTS: We identified 47 patients who underwent splenectomy and 454 who did not during primary or interval cytoreductive surgery. Final stage was IIIB in 1 (2.1%), IIIC in 26 (55.3%), IVA in 7 (14.9%), and IVB in 13 (27.7%) patients. Those with splenectomy had significantly higher stage. Surgery duration and hospital length of stay were longer and blood transfusion more common after splenectomy, but there were no differences in post-operative infection, readmission, or overall survival. Pancreatic leaks were seen in 4/47 (8.5%) patients. Post-splenectomy vaccinations were documented in 42/47 (89.4%) patients. Only 2/47 (4.3%) received post-splenectomy discharge instructions and 3/7 (42.9%) received aspirin for platelets 1 million or more. CONCLUSIONS: While splenectomy adds morbidity, it continues to offer benefit in those patients who can achieve optimal cytoreduction. Areas for quality improvement in post-splenectomy care include receipt of vaccinations, patient discharge information, and timely pancreatic fistula management.

A corepressor participates in LexA-independent regulation of error-prone polymerases in Acinetobacter.

The DNA damage response of the multidrug-resistant pathogen Acinetobacter baumannii, which induces mutagenic UmuD'2C error-prone polymerases, differs from that of many bacteria. Acinetobacter species lack a LexA repressor, but induce gene transcription after DNA damage. One regulator, UmuDAb, binds to and represses the promoters of the multiple A. baumannii ATCC 17978 umuDC alleles and the divergently transcribed umuDAb and ddrR genes. ddrR is unique to the genus Acinetobacter and of unknown function. 5' RACE (rapid amplification of cDNA ends) PCR mapping of the umuDAb and ddrR transcriptional start sites revealed that their -35 promoter elements overlapped the UmuDAb binding site, suggesting that UmuDAb simultaneously repressed expression of both genes by blocking polymerase access. This coordinated control of ddrR and umuDAb suggested that ddrR might also regulate DNA damage-inducible gene transcription. RNA-sequencing experiments in 17 978 ddrR- cells showed that ddrR regulated approximately 25 % (n=39) of the mitomycin C-induced regulon, with umuDAb coregulating 17 of these ddrR-regulated genes. Eight genes (the umuDC polymerases, umuDAb and ddrR) were de-repressed in the absence of DNA damage, and nine genes were uninduced in the presence of DNA damage, in both ddrR and umuDAb mutant strains. These data suggest ddrR has multiple roles, both as a co-repressor and as a positive regulator of DNA damage-inducible gene transcription. Additionally, 57 genes were induced by mitomycin C in the ddrR mutant but not in wild-type cells. This regulon contained multiple genes for DNA replication, recombination and repair, transcriptional regulators, RND efflux, and transport. This study uncovered another regulator of the atypical DNA damage response of this genus, to help describe how this pathogen acquires drug resistance through its expression of the error-prone polymerases under DdrR and UmuDAb control.

Synthesis, Characterization, and Biological Activity of Hybrid Thiosemicarbazone-Alkylthiocarbamate Metal Complexes.

A series of hybrid ligands (H2L1-H2L3) derived from 4-methyl-3-thiosemicarbazide and hydrazinecarbothioic acid O-alkyl esters were synthesized and characterized by NMR. The ligands were chelated with copper (4-6), nickel (7-9), and zinc (10-12) and characterized by spectroscopy, electrochemistry, and single crystal X-ray crystallography. The chelated metals displayed substantial anodic shifts in the CuII/I reduction potential of ∼160 mV relative to their bis(thiosemicarbazone) analogues. The metal chelates 4-12 were evaluated for potential anticancer activity by MTT assays, and selected results were confirmed by clonogenic and trypan blue assays. The copper derivatives 4 and 6 were found to have potent and cancer-selective antiproliferative effects, with GI50 values less than 100 nM in A549 lung adenocarcinoma cells compared with at least 20-fold less activity in IMR90 nonmalignant lung fibroblasts. In comparison, the nickel complexes were much less active and had little cancer-selectivity. Varying by ligand, the zinc complexes were less potent or had comparable activity compared to that of the corresponding copper complex. UV-visible spectroscopy indicated that zinc complex 10 was transmetalated in the presence of equimolar copper, whereas nickel complex 7 was not. Copper complexes 4 and 6 were also assessed in the NCI60 screen and were found to have cytotoxic activity against most solid tumor cell lines. In MTT assays, 4 and 6 were substantially more active against A549 cancer cells than Cu(ATSM) and were more cancer-selective (for A549 compared to IMR-90) than Cu(GTSM). Our results suggest that hybrid thiosemicarbazone-alkylthiocarbamate copper complexes have potential for development as new anticancer agents.

Incorporating local adaptation into forecasts of species' distribution and abundance under climate change.

Populations of many species are genetically adapted to local historical climate conditions. Yet most forecasts of species' distributions under climate change have ignored local adaptation (LA), which may paint a false picture of how species will respond across their geographic ranges. We review recent studies that have incorporated intraspecific variation, a potential proxy for LA, into distribution forecasts, assess their strengths and weaknesses, and make recommendations for how to improve forecasts in the face of LA. The three methods used so far (species distribution models, response functions, and mechanistic models) reflect a trade-off between data availability and the ability to rigorously demonstrate LA to climate. We identify key considerations for incorporating LA into distribution forecasts that are currently missing from many published studies, including testing the spatial scale and pattern of LA, the confounding effects of LA to nonclimatic or biotic drivers, and the need to incorporate empirically based dispersal or gene flow processes. We suggest approaches to better evaluate these aspects of LA and their effects on species-level forecasts. In particular, we highlight demographic and dynamic evolutionary models as promising approaches to better integrate LA into forecasts, and emphasize the importance of independent model validation. Finally, we urge closer examination of how LA will alter the responses of central vs. marginal populations to allow stronger generalizations about changes in distribution and abundance in the face of LA.

Altered Met receptor phosphorylation and LRP1-mediated uptake in cells lacking carbohydrate-dependent lysosomal targeting.

Acid hydrolases utilize a carbohydrate-dependent mechanism for lysosomal targeting. These hydrolases acquire a mannose 6-phosphate tag by the action of the GlcNAc-1-phosphotransferase enzyme, allowing them to bind receptors and traffic to endosomes. Loss of GlcNAc-1-phosphotransferase results in hydrolase hypersecretion and profound lysosomal storage. Little, however, is known about how these cellular phenotypes affect the trafficking, activity, and localization of surface glycoproteins. To address this question, we profiled the abundance of surface glycoproteins in WT and CRISPR-mediated GNPTAB-/- HeLa cells and identified changes in numerous glycoproteins, including the uptake receptor LRP1 and multiple receptor tyrosine kinases. Decreased cell surface LRP1 in GNPTAB-/- cells corresponded with a reduction in its steady-state level and less amyloid-ß-40 (Aß40) peptide uptake. GNPTAB-/- cells displayed elevated activation of several kinases including Met receptor. We found increased Met phosphorylation within both the kinase and the docking domains and observed that lower concentrations of pervanadate were needed to cause an increase in phospho-Met in GNPTAB-/- cells. Together, these data suggested a decrease in the activity of the receptor and non-receptor protein-tyrosine phosphatases that down-regulate Met phosphorylation. GNPTAB-/- cells exhibited elevated levels of reactive oxygen species, known to inactivate cell surface and cytosolic phosphatases by oxidation of active site cysteine residues. Consistent with this mode of action, peroxide treatment of parental HeLa cells elevated phospho-Met levels whereas antioxidant treatment of GNPTAB-/- cells reduced phospho-Met levels. Collectively, these findings identify new mechanisms whereby impaired lysosomal targeting can impact the activity and recycling of receptors.

Both life-history plasticity and local adaptation will shape range-wide responses to climate warming in the tundra plant Silene acaulis.

Many predictions of how climate change will impact biodiversity have focused on range shifts using species-wide climate tolerances, an approach that ignores the demographic mechanisms that enable species to attain broad geographic distributions. But these mechanisms matter, as responses to climate change could fundamentally differ depending on the contributions of life-history plasticity vs. local adaptation to species-wide climate tolerances. In particular, if local adaptation to climate is strong, populations across a species' range-not only those at the trailing range edge-could decline sharply with global climate change. Indeed, faster rates of climate change in many high latitude regions could combine with local adaptation to generate sharper declines well away from trailing edges. Combining 15 years of demographic data from field populations across North America with growth chamber warming experiments, we show that growth and survival in a widespread tundra plant show compensatory responses to warming throughout the species' latitudinal range, buffering overall performance across a range of temperatures. However, populations also differ in their temperature responses, consistent with adaptation to local climate, especially growing season temperature. In particular, warming begins to negatively impact plant growth at cooler temperatures for plants from colder, northern populations than for those from warmer, southern populations, both in the field and in growth chambers. Furthermore, the individuals and maternal families with the fastest growth also have the lowest water use efficiency at all temperatures, suggesting that a trade-off between growth and water use efficiency could further constrain responses to forecasted warming and drying. Taken together, these results suggest that populations throughout species' ranges could be at risk of decline with continued climate change, and that the focus on trailing edge populations risks overlooking the largest potential impacts of climate change on species' abundance and distribution.

Managing Celiac Disease for Women: Implications for the Primary Care Provider.

Although many people have symptoms of celiac disease, it can take a while to diagnose. Villous atrophy may be present long before any gastrointestinal symptoms. An important point to acknowledge is that celiac disease could be identified earlier in some women with a positive family history. The disease also could be the cause of some women's reproductive problems. Primary care providers, using comprehensive history taking, are in the unique position to identify individuals who may have celiac disease, assist women in gaining knowledge about a gluten-free diet, order diagnostic testing, and refer to a gastroenterologist. The positive change in fertility with a simultaneous improvement of nutrient deficiencies shortly after adopting a gluten-free diet indicates a possible link between such nutrients and sex hormone function. High levels of homocysteine, which can negatively impact fertility, have also been linked to individuals with problems, such as celiac disease, that decrease vitamin B12 absorption. The purpose of this article is to review the literature and the evidence-based care guidelines for comprehensive screening, diagnostics, and pathophysiology of celiac disease, with a specific focus on the female reproductive system, anemia management, and gluten-free diet integration.

Mating system plasticity promotes persistence and adaptation of colonizing populations of hermaphroditic angiosperms.

Persistence and adaptation in novel environments are limited by small population size, strong selection, and maladaptive gene flow. Mating system plasticity is common in angiosperms and may provide both demographic and genetic benefits that promote niche evolution, including reproductive assurance and isolation from maladaptive gene flow. Yet increased self-fertilization may also cause inbreeding depression, accumulation of deleterious mutations, and reduced adaptive potential. Here we use individual-based simulations to examine the consequences of mating system plasticity for persistence and adaptation in a novel environment that imposes selection on a quantitative trait. We examine the joint evolution of local adaptation, inbreeding depression, and genetic load. We find that a plastic shift to a mixed mating system generally promotes niche evolution by decreasing the risk of extinction, providing isolation from maladaptive gene flow, and temporarily increasing genetic variance in the trait under selection, whereas obligate self-fertilization reduces adaptive potential. These effects are most pronounced under conditions of mate limitation, strong selection, or maladaptive gene flow. Our results highlight the diverse demographic and genetic consequences of self-fertilization and support the potential role for plastic shifts in mating system to promote niche evolution in flowering plants.

An ultraviolet floral polymorphism associated with life history drives pollinator discrimination in Mimulus guttatus.

UNLABELLED: • PREMISE OF THE STUDY: Ultraviolet (UV) floral patterns are common in angiosperms and mediate pollinator attraction, efficiency, and constancy. UV patterns may vary within species, yet are cryptic to human observers. Thus, few studies have explicitly described the distribution or ecological significance of intraspecific variation in UV floral patterning. Here, we describe the geographic distribution and pattern of inheritance of a UV polymorphism in the model plant species Mimulus guttatus (Phrymaceae). We then test whether naturally occurring UV phenotypes influence pollinator interactions within M. guttatus.• METHODS: We document UV patterns in 18 annual and 19 perennial populations and test whether UV pattern is associated with life history. To examine the pattern of inheritance, we conducted crosses within and between UV phenotypes. Finally, we tested whether bee pollinators discriminate among naturally occurring UV phenotypes in two settings: wild bee communities and captive Bombus impatiens.• KEY RESULTS: Within M. guttatus, perennial populations exhibit a small bulls-eye pattern, whereas a bilaterally symmetric runway pattern occurs mainly in annual populations. Inheritance of UV patterning is consistent with a single-locus Mendelian model in which the runway phenotype is dominant. Bee pollinators discriminate against unfamiliar UV patterns in both natural and controlled settings.• CONCLUSIONS: We describe a widespread UV polymorphism associated with life history divergence within Mimulus guttatus. UV pattern influences pollinator visitation and should be considered when estimating reproductive barriers between life history ecotypes. This work develops a new system to investigate the ecology and evolution of UV floral patterning in a species with extensive genomic resources.

A nondiscriminating glutamyl-tRNA synthetase in the plasmodium apicoplast: the first enzyme in an indirect aminoacylation pathway.

The malaria parasite Plasmodium falciparum and related organisms possess a relict plastid known as the apicoplast. Apicoplast protein synthesis is a validated drug target in malaria because antibiotics that inhibit translation in prokaryotes also inhibit apicoplast protein synthesis and are sometimes used for malaria prophylaxis or treatment. We identified components of an indirect aminoacylation pathway for Gln-tRNA(Gln) biosynthesis in Plasmodium that we hypothesized would be essential for apicoplast protein synthesis. Here, we report our characterization of the first enzyme in this pathway, the apicoplast glutamyl-tRNA synthetase (GluRS). We expressed the recombinant P. falciparum enzyme in Escherichia coli, showed that it is nondiscriminating because it glutamylates both apicoplast tRNA(Glu) and tRNA(Gln), determined its kinetic parameters, and demonstrated its inhibition by a known bacterial GluRS inhibitor. We also localized the Plasmodium berghei ortholog to the apicoplast in blood stage parasites but could not delete the PbGluRS gene. These data show that Gln-tRNA(Gln) biosynthesis in the Plasmodium apicoplast proceeds via an essential indirect aminoacylation pathway that is reminiscent of bacteria and plastids.

Impact of an over-the-counter "sleep lotion" on human salivary melatonin levels and sleep quality: a randomized controlled trial.

OBJECTIVE: To compare the impact of a commercial "sleep lotion" versus a placebo control lotion on salivary melatonin and sleep quality. METHODS: The presence of melatonin in the lotion was confirmed and quantitated with High Performance Liquid Chromatography (HPLC). In this randomized, controlled, double-blind crossover trial, undergraduate student participants applied lotions on two separate nights and we quantitated melatonin in saliva samples with enzyme linked immunosorbent assays. We also assessed sleep quality with a modified Pittsburgh Sleep Quality Index. CLINICALTRIALS: gov ID NCT06053385. RESULTS: Sixty-three participants (age 20.5 ± 1.2 years; 81% female) enrolled in the study and provided at least one saliva sample. The sleep lotion contained 0.24 ± 0.01% melatonin (g/100 g lotion) which dramatically impacted salivary melatonin levels, increasing them up to ~1000 fold compared to the placebo lotion (n = 36 participants with all six timepoints). The lotion improved sleep quality in a subsample of the poor sleepers (n = 18). However, the sleep quality in the overall sample was not significantly different on the active versus placebo lotion nights. CONCLUSION: In a small undergraduate student sample, a commercial melatonin-containing lotion improved sleep in those with poor sleep quality. Caution should be taken by consumers using over-the-counter melatonin lotions because the undisclosed dosage can be high and well absorbed by the skin.

Clinical Outcomes of Human Rhinovirus/Enterovirus Infection in Pediatric Hemopoietic Cell Transplant Patients.

BACKGROUND: Respiratory viral infections are common among pediatric transplant patients, with human rhinovirus (HRV) being the most frequent. In pediatric patients undergoing hemopoietic cell transplant (HCT), infection with HRV has been associated with progression to lower respiratory tract infection (LRTI) and adverse outcomes. We describe the clinical presentation and outcomes of HRV infection in children undergoing HCT. METHODS: Single-center retrospective study. HCT recipients who were positive for HRV/EV (HRV+) or negative for any respiratory virus (VN) by BioFire® FilmArray® panel between October 2014 and December 2017, were included. Primary outcomes were progression to LRTI, ICU admission, all-cause mortality at 3 and 6 months, and respiratory event-related mortality at 6 months. RESULTS: 227 patients (160 allogeneic HCT) were included. Of all patients, 108/227 (47.6%) were HRV+. From all HRV+, 95/108 (88%) were symptomatic and 68/107 (63.6%) of the diagnosis were made pretransplant. The median age of HRV+ was significantly lower than VN patients (5 vs 10 years). Cough and rhinorrhea were more frequently observed in HRV+ (53.7 and 60% vs 19.8 and 22.8%, respectively). No differences were found between both groups pretransplant and overall in rates progression to LRTI, ICU admission, mechanical ventilation, all-cause within 3 and 6 months, and mortality related with respiratory failure. No significant association was found between the severity of respiratory disease and the type of conditioning, type of transplant, or absolute lymphocyte count. CONCLUSIONS: HRV infection is frequently detected in HCT recipients but is not associated with severity of respiratory disease, need for intensive care unit or mortality, including those diagnosed before transplant, suggesting that delaying HCT in this scenario may not be needed. Multicenter larger studies are required to confirm these findings.

The impact of the COVID-19 pandemic on vaccination uptake in the United States and strategies to recover and improve vaccination rates: A review.

The COVID-19 pandemic disrupted routine healthcare delivery, causing declines in CDC-recommended vaccination rates across the life-course in the United States (US). Ensuring protection against disease outbreaks and associated morbidity and mortality depends on improving vaccine coverage rates (VCRs) and uptake. The authors conducted a targeted literature review to assess the pandemic's effects on routine vaccination rates across different populations, evaluating VCR recovery and improvement efforts. The review highlights articles published with data measuring or evaluating VCR decline across the US during the COVID-19 pandemic from January 2020 to April 2022, associated health impacts, and policy and programmatic strategies to recover routine VCRs. While vaccination rates stagnated or declined across some populations pre-pandemic, the review indicated there were further VCR declines in 2020 and 2021 compared to 2019 across numerous CDC-recommended vaccines, ages, and geographies, with some vaccines and sub-populations disproportionally impacted. The review additionally identified declines in patient healthcare visit frequency and increases in morbidity and mortality associated with vaccine-preventable disease (VPD) complications. Reviewed publications highlighted multifaceted strategies that could aid in recovering VCRs. Overall, findings demonstrate a significant reduction in VCRs across all age groups and highlight promising solutions to inform vaccine uptake efforts and ensure broader protection against VPDs.

Clinical Correlation of Adenoviral Load in the Respiratory Tract Measured by Digital PCR in Immunocompromised Children.

Immunocompromised patients can have life-threatening adenoviral infection. Viral load in blood and stool is commonly used to guide antiviral therapy. We developed and evaluated a digital polymerase chain reaction assay to quantify human adenovirus in the respiratory tract and showed that higher peak load correlates with disseminated infection, mechanical ventilation, and death.