Integration of ζ-deficient CARs into the CD3ζ gene conveys potent cytotoxicity in T and NK cells.

ABSTRACT: Chimeric antigen receptor (CAR)-redirected immune cells hold significant therapeutic potential for oncology, autoimmune diseases, transplant medicine, and infections. All approved CAR-T therapies rely on personalized manufacturing using undirected viral gene transfer, which results in nonphysiological regulation of CAR-signaling and limits their accessibility due to logistical challenges, high costs and biosafety requirements. Random gene transfer modalities pose a risk of malignant transformation by insertional mutagenesis. Here, we propose a novel approach utilizing CRISPR-Cas gene editing to redirect T cells and natural killer (NK) cells with CARs. By transferring shorter, truncated CAR-transgenes lacking a main activation domain into the human CD3ζ (CD247) gene, functional CAR fusion-genes are generated that exploit the endogenous CD3ζ gene as the CAR's activation domain. Repurposing this T/NK-cell lineage gene facilitated physiological regulation of CAR expression and redirection of various immune cell types, including conventional T cells, TCRγ/δ T cells, regulatory T cells, and NK cells. In T cells, CD3ζ in-frame fusion eliminated TCR surface expression, reducing the risk of graft-versus-host disease in allogeneic off-the-shelf settings. CD3ζ-CD19-CAR-T cells exhibited comparable leukemia control to TCRα chain constant (TRAC)-replaced and lentivirus-transduced CAR-T cells in vivo. Tuning of CD3ζ-CAR-expression levels significantly improved the in vivo efficacy. Notably, CD3ζ gene editing enabled redirection of NK cells without impairing their canonical functions. Thus, CD3ζ gene editing is a promising platform for the development of allogeneic off-the-shelf cell therapies using redirected killer lymphocytes.

Oscillatory vs. non-oscillatory subthalamic beta activity in Parkinson's disease.

Parkinson's disease is characterized by exaggerated beta activity (13-35 Hz) in cortico-basal ganglia motor loops. Beta activity includes both periodic fluctuations (i.e. oscillatory activity) and aperiodic fluctuations reflecting spiking activity and excitation/inhibition balance (i.e. non-oscillatory activity). However, the relative contribution, dopamine dependency and clinical correlations of oscillatory vs. non-oscillatory beta activity remain unclear. We recorded, modelled and analysed subthalamic local field potentials in parkinsonian patients at rest while off or on medication. Autoregressive modelling with additive 1/f noise clarified the relationships between measures of beta activity in the time domain (i.e. amplitude and duration of beta bursts) or in the frequency domain (i.e. power and sharpness of the spectral peak) and oscillatory vs. non-oscillatory activity: burst duration and spectral sharpness are specifically sensitive to oscillatory activity, whereas burst amplitude and spectral power are ambiguously sensitive to both oscillatory and non-oscillatory activity. Our experimental data confirmed the model predictions and assumptions. We subsequently analysed the effect of levodopa, obtaining strong-to-extreme Bayesian evidence that oscillatory beta activity is reduced in patients on vs. off medication, with moderate evidence for absence of modulation of the non-oscillatory component. Finally, specifically the oscillatory component of beta activity correlated with the rate of motor progression of the disease. Methodologically, these results provide an integrative understanding of beta-based biomarkers relevant for adaptive deep brain stimulation. Biologically, they suggest that primarily the oscillatory component of subthalamic beta activity is dopamine dependent and may play a role not only in the pathophysiology but also in the progression of Parkinson's disease. KEY POINTS: Beta activity in Parkinson's disease includes both true periodic fluctuations (i.e. oscillatory activity) and aperiodic fluctuations reflecting spiking activity and synaptic balance (i.e. non-oscillatory activity). The relative contribution, dopamine dependency and clinical correlations of oscillatory vs. non-oscillatory beta activity remain unclear. Burst duration and spectral sharpness are specifically sensitive to oscillatory activity, while burst amplitude and spectral power are ambiguously sensitive to both oscillatory and non-oscillatory activity. Only the oscillatory component of subthalamic beta activity is dopamine-dependent. Stronger beta oscillatory activity correlates with faster motor progression of the disease.

Study on the Association between Cesarean Section Birth and Asthma Risk in the Pediatric Population of the Health Area of Palencia between 1993 and 2020.

INTRODUCTION AND OBJECTIVES: Both asthma prevalence and the percentage of cesarean sections have increased in parallel in recent years. Research studies suggest an increased risk of developing atopic diseases and asthma after cesarean section birth compared to vaginal delivery. The main objective of this study is to analyze the risk of asthma admission after cesarean section birth compared to vaginal delivery in the pediatric population. POPULATION AND METHODS: Retrospective observational analytical case-control study from 1993 to 2020. The cases include all admitted patients to our health area hospital, for patients aged 7 to 16 diagnosed with asthma. For each case, a control without a diagnosis of asthma is selected with the same age, and that has also caused an episode of admission. RESULTS: A total of 290 admission episodes with a diagnosis of asthma were obtained, caused by 155 patients. Out of these, 145 cases with documented delivery types were selected. For cases, 155 controls were selected. The historical proportion of cesarean sections in the asthmatic group is 18.6%, compared to 14.2% in the non-asthmatic group. There is a statistically non-significant difference of 4.4% more cesarean sections in the asthmatic group compared to the control group. DISCUSSION: We have not demonstrated a statistically significant association between being born by cesarean section and an increased risk of asthma admission. Based on this finding, we cannot conclude that there is an association between being born by cesarean section and a higher risk of suffering from asthma, unlike what has been postulated in other research studies.

In Vitro Evaluation of Soft Contact Lens Wettability With a Nonmodified Commercial Videokeratoscope.

PURPOSE: To evaluate a new in vitro technique for measuring soft contact lens wettability using a nonmodified commercial videokeratoscope, the Medmont E300. To this end, the capability of different artificial tears containing hyaluronic acid (HA) to improve soft contact lens wettability in vitro was investigated. METHODS: An experimental in vitro study was conducted to assess the wetting properties of three artificial tears containing different concentrations of HA (0.1%, 0.2%, and 0.3%) on soft contact lenses. A saline solution was used as the control. For each solution, 15 hydrogel (Ocufilcon D) contact lenses and 15 silicone-hydrogel (Somofilcon A) contact lenses were evaluated. The in vitro wettability of the lenses was measured using the Medmont E300 with a self-developed technique, which involved measuring the tear film surface quality (TFSQ) mean, TFSQ area, TFSQ central, and TFSQ inferior. RESULTS: Compared with the saline solution, all the concentration of HA (0.1%, 0.2%, and 0.3%) improved the in vitro wettability of both soft contact lenses by decreasing their TFSQ mean and TFSQ area ( P <0.05). Regression models revealed an exponential relationship between contact lens wettability and the concentration of HA for both soft contact lenses ( R >0.5, P <0.05). Furthermore, the hydrogel contact lens presented a wetter surface than the silicone-hydrogel contact lens ( P <0.05). CONCLUSIONS: The measurement of in vitro wettability of soft contact lenses with a nonmodified Medmont E300 seems to be a useful technique to evaluate the wetting properties of contact lens products.

How Streptococcus suis escapes antibiotic treatments.

Streptococcus suis is a zoonotic agent that causes sepsis and meningitis in pigs and humans. S. suis infections are responsible for large economic losses in pig production. The lack of effective vaccines to prevent the disease has promoted the extensive use of antibiotics worldwide. This has been followed by the emergence of resistance against different classes of antibiotics. The rates of resistance to tetracyclines, lincosamides, and macrolides are extremely high, and resistance has spread worldwide. The genetic origin of S. suis resistance is multiple and includes the production of target-modifying and antibiotic-inactivating enzymes and mutations in antibiotic targets. S. suis genomes contain traits of horizontal gene transfer. Many mobile genetic elements carry a variety of genes that confer resistance to antibiotics as well as genes for autonomous DNA transfer and, thus, S. suis can rapidly acquire multiresistance. In addition, S. suis forms microcolonies on host tissues, which are associations of microorganisms that generate tolerance to antibiotics through a variety of mechanisms and favor the exchange of genetic material. Thus, alternatives to currently used antibiotics are highly demanded. A deep understanding of the mechanisms by which S. suis becomes resistant or tolerant to antibiotics may help to develop novel molecules or combinations of antimicrobials to fight these infections. Meanwhile, phage therapy and vaccination are promising alternative strategies, which could alleviate disease pressure and, thereby, antibiotic use.

Prevalence of Heterotrophic Methylmercury Detoxifying Bacteria across Oceanic Regions.

Microbial reduction of inorganic divalent mercury (Hg2+) and methylmercury (MeHg) demethylation is performed by the mer operon, specifically by merA and merB genes, respectively, but little is known about the mercury tolerance capacity of marine microorganisms and its prevalence in the ocean. Here, combining culture-dependent analyses with metagenomic and metatranscriptomic data, we show that marine bacteria that encode mer genes are widespread and active in the global ocean. We explored the distribution of these genes in 290 marine heterotrophic bacteria (Alteromonas and Marinobacter spp.) isolated from different oceanographic regions and depths, and assessed their tolerance to diverse concentrations of Hg2+ and MeHg. In particular, the Alteromonas sp. ISS312 strain presented the highest tolerance capacity and a degradation efficiency for MeHg of 98.2% in 24 h. Fragment recruitment analyses of Alteromonas sp. genomes (ISS312 strain and its associated reconstructed metagenome assembled genome MAG-0289) against microbial bathypelagic metagenomes confirm their prevalence in the deep ocean. Moreover, we retrieved 54 merA and 6 merB genes variants related to the Alteromonas sp. ISS312 strain from global metagenomes and metatranscriptomes from Tara Oceans. Our findings highlight the biological reductive MeHg degradation as a relevant pathway of the ocean Hg biogeochemical cycle.

Economic impact of comorbid TBI-dementia on VA facility and non-VA facility costs, 2000-2020.

OBJECTIVE: There is evidence Traumatic Brain Injury (TBI) is associated with increased risk of dementia (D). We compared VA and non-VA facility costs associated with TBI+D and each diagnosis alone, relative to neither diagnosis, annually and over time, 2000-2020. METHODS: We estimated adjusted panel models of annual VHA costs in VA and non-VA facilities, stratified by age, and by TBI-dementia status. We also estimated cost for the TBI+D cohort by time since TBI and dementia diagnoses. All costs were 2021 inflation adjusted. RESULTS: Veterans <65 ($30,736) and ≥65 ($15,650) with TBI+D, while veterans <65 ($3,379) and ≥65 ($4,252) with TBI-only had higher annual total VHA costs, relative to neither diagnosis. Veterans with TBI+D < 65 ($42,864) and ≥65 ($72,424) had higher costs in years≥15 after TBI diagnosis, while <65 ($36,431) and ≥65 ($37,589) had higher costs in years ≥10 after dementia diagnosis. CONCLUSIONS: The main cost driver was inpatient non-VA facility costs. Veterans had continuously increasing inpatient care costs in non-VA facilities over time since their TBI and dementia diagnoses. Given budget constraints on the VA system, quality of care in non-VA facilities warrants comparison with VA facilities to make informed decisions regarding referrals to non-VA facilities.

Superconducting Sr2RuO4 Thin Films without Out-of-Phase Boundaries by Higher-Order Ruddlesden-Popper Intergrowth.

Ruddlesden-Popper (RP) phases (An+1BnO3n+1, n = 1, 2,···) have attracted intensive research with diverse functionalities for device applications. However, the realization of a high-quality RP-phase film is hindered by the formation of out-of-phase boundaries (OPBs) that occur at terrace edges, originating from lattice mismatch in the c-axis direction with the A'B'O3 (n = ∞) substrate. Here, using strontium ruthenate RP-phase Sr2RuO4 (n = 1) as a model system, an experimental approach for suppressing OPBs was developed. By tuning the growth parameters, the Sr3Ru2O7 (n = 2) phase was formed in a controlled manner near the film-substrate interface. This higher-order RP-phase then blocked the subsequent formation of OPBs, resulting in nearly defect-free Sr2RuO4 layer at the upper region of the film. Consequently, the Sr2RuO4 thin films exhibited superconductivity up to 1.15 K, which is the highest among Sr2RuO4 films grown by pulsed laser deposition. This work paves the way for synthesizing pristine RP-phase heterostructures and exploring their unique physical properties.

Generation of the First Human In Vitro Model for McArdle Disease Based on iPSC Technology.

McArdle disease is a rare autosomal recessive disorder caused by mutations in the PYGM gene. This gene encodes for the skeletal muscle isoform of glycogen phosphorylase (myophosphorylase), the first enzyme in glycogenolysis. Patients with this disorder are unable to obtain energy from their glycogen stored in skeletal muscle, prompting an exercise intolerance. Currently, there is no treatment for this disease, and the lack of suitable in vitro human models has prevented the search for therapies against it. In this article, we have established the first human iPSC-based model for McArdle disease. For the generation of this model, induced pluripotent stem cells (iPSCs) from a patient with McArdle disease (harbouring the homozygous mutation c.148C>T; p.R50* in the PYGM gene) were differentiated into myogenic cells able to contract spontaneously in the presence of motor neurons and generate calcium transients, a proof of their maturity and functionality. Additionally, an isogenic skeletal muscle model of McArdle disease was created. As a proof-of-concept, we have tested in this model the rescue of PYGM expression by two different read-through compounds (PTC124 and RTC13). The developed model will be very useful as a platform for testing drugs or compounds with potential pharmacological activity.

Usher Syndrome: Genetics of a Human Ciliopathy.

Usher syndrome (USH) is an autosomal recessive syndromic ciliopathy characterized by sensorineural hearing loss, retinitis pigmentosa and, sometimes, vestibular dysfunction. There are three clinical types depending on the severity and age of onset of the symptoms; in addition, ten genes are reported to be causative of USH, and six more related to the disease. These genes encode proteins of a diverse nature, which interact and form a dynamic protein network called the "Usher interactome". In the organ of Corti, the USH proteins are essential for the correct development and maintenance of the structure and cohesion of the stereocilia. In the retina, the USH protein network is principally located in the periciliary region of the photoreceptors, and plays an important role in the maintenance of the periciliary structure and the trafficking of molecules between the inner and the outer segments of photoreceptors. Even though some genes are clearly involved in the syndrome, others are controversial. Moreover, expression of some USH genes has been detected in other tissues, which could explain their involvement in additional mild comorbidities. In this paper, we review the genetics of Usher syndrome and the spectrum of mutations in USH genes. The aim is to identify possible mutation associations with the disease and provide an updated genotype-phenotype correlation.

Exome sequencing identifies PEX6 mutations in three cases diagnosed with Retinitis Pigmentosa and hearing impairment.

Purpose: The aim of the present work is the molecular diagnosis of three patients with deafness and retinal degeneration. Methods: Three patients from two unrelated families were initially analyzed with custom gene panels for Usher genes, non-syndromic hearing loss, or inherited syndromic retinopathies and further investigated by means of clinical or whole exome sequencing. Results: The study allowed us to detect likely pathogenic variants in PEX6, a gene typically involved in peroxisomal biogenesis disorders (PBDs). Beside deaf-blindness, both families showed additional features: Siblings from Family 1 showed enamel alteration and abnormal peroxisome. In addition, the brother had mild neurodevelopmental delay and nephrolithiasis. The case II:1 from Family 2 showed intellectual disability, enamel alteration, and dysmorphism. Conclusions: We have reported three new cases with pathogenic variants in PEX6 presenting with milder forms of the Zellweger spectrum disorders (ZSD). The three cases showed distinct clinical features. Thus, expanding the phenotypic spectrum of PBDs and ascertaining exome sequencing is an effective strategy for an accurate diagnosis of clinically overlapping and genetically heterogeneous disorders such as deafness-blindness association.

Independent and Joint-GWAS for growth traits in Eucalyptus by assembling genome-wide data for 3373 individuals across four breeding populations.

Genome-wide association studies (GWAS) in plants typically suffer from limited statistical power. An alternative to the logistical and cost challenge of increasing sample sizes is to gain power by meta-analysis using information from independent studies. We carried out GWAS for growth traits with six single-marker models and regional heritability mapping (RHM) in four Eucalyptus breeding populations independently and by Joint-GWAS, using gene and segment-based models, with data for 3373 individuals genotyped with a communal EUChip60KSNP platform. While single-single nucleotide polymorphism (SNP) GWAS hardly detected significant associations at high-stringency in each population, gene-based Joint-GWAS revealed nine genes significantly associated with tree height. Associations detected using single-SNP GWAS, RHM and Joint-GWAS set-based models explained on average 3-20% of the phenotypic variance. Whole-genome regression, conversely, captured 64-89% of the pedigree-based heritability in all populations. Several associations independently detected for the same SNPs in different populations provided unprecedented GWAS validation results in forest trees. Rare and common associations were discovered in eight genes involved in cell wall biosynthesis and lignification. With the increasing adoption of genomic prediction of complex phenotypes using shared SNPs and much larger tree breeding populations, Joint-GWAS approaches should provide increasing power to pinpoint discrete associations potentially useful toward tree breeding and molecular applications.

Bioelectrical impedance vector values in a Spanish healthy newborn population for nutritional assessment.

INTRODUCTION: Vector bioimpedance analysis (BIVA) can be very useful for the evaluation of body composition, hydration, and nutritional status in infants and newborns. The objective of this study was to determine the impedance vector distribution for a group of healthy newborn Spanish children. METHODS: This was a cross-sectional, descriptive study conducted with 154 healthy, Spanish newborns (gestational age: 37-41 weeks) aged 24 to 72 hours (79 males, 75 females). Weight, height, and cephalic-circumference were determined. Resistance and reactance were measured with a single-frequency impedance analyzer at 50 kHz (tetrapolar analysis). The newborns' specific 95% confidence intervals of the mean vectors and the 95%, 75%, and 50% tolerance intervals for the individual vector measurements were plotted using R and Xc components standardized by the subjects' lengths. The mean impedance vectors were compared with Hotelling's-T2 test for vector analysis (significance level: P < .05). RESULTS: The newborns exhibited gender-related differences in the mean impedance vector (mean [SD] R/H: 833.6 [97.5] Ohm/m in males vs 918.2 [107.7] Ohm/m in females; mean [SD] Xc/H: 91.3 [34.7] Ohm/m in males vs 95.6 [23.2] Ohm/m in females). No statistically significant differences in the mean impedance vectors were observed according to days of life. Lower values of resistance and slightly higher reactance values were observed in the healthy Spanish newborns compared to Italian newborns. CONCLUSIONS: New tolerance ellipses were constructed for healthy Spanish newborns. These data allow detecting alterations in the hydration status and cell mass in term newborns in the first 3 days of life.

Epidural Space Identification With Loss of Resistance Technique for Epidural Analgesia During Labor: A Randomized Controlled Study Using Air or Saline-New Arguments for an Old Controversy.

BACKGROUND: The best technique to identify the epidural space for labor analgesia is still unclear despite the publication of various randomized controlled studies and meta-analyses. Our aim was to assess the superiority of the saline loss of resistance (SLOR) technique over the air loss of resistance (ALOR) technique with respect to the quality of the block. METHODS: Consenting parturients admitted to our obstetric suite for spontaneous or induced labor were randomized to receive epidural analgesia using either the ALOR or SLOR technique. Our primary outcome was to compare the impact of the SLOR and ALOR technique on pain score improvement measured 30 minutes after administration of epidural block. Our secondary outcomes included the density of motor blockade and analgesic efficacy measured at 30 minutes. Primary and secondary outcomes were compared using the Student t test and Mann-Whitney U test. Statistical significance was set at P < .017 for primary and secondary outcomes, considering Bonferroni correction for multiple comparisons. Other comparisons were considered exploratory. RESULTS: Four hundred parturients were included; 24 were excluded from the final analysis. After 30 minutes, pain score reduction (ALOR, 4.7 ± 2.9/10; SLOR, 4.9 ± 3.0/10; P = .49), motor block (ALOR, 1.4 ± 0.8; SLOR, 1.3 ± 0.8; P = .27), and efficacy of the block (ALOR, 1.0 ± 0.7; SLOR, 1.0 ± 0.6; P = .87) did not differ significantly between groups. CONCLUSIONS: Pain score reduction after 30 minutes and onset of the block were not affected by the technique used to locate the epidural space.

Respiratory Syncytial Virus Genotypes, Host Immune Profiles, and Disease Severity in Young Children Hospitalized With Bronchiolitis.

Background: Data on how respiratory syncytial virus (RSV) genotypes influence disease severity and host immune responses is limited. Here, we characterized the genetic variability of RSV during 5 seasons, and evaluated the role of RSV subtypes, genotypes, and viral loads in disease severity and host transcriptional profiles. Methods: A prospective, observational study was carried out, including a convenience sample of healthy infants hospitalized with RSV bronchiolitis. Nasopharyngeal samples for viral load quantitation, typing, and genotyping, and blood samples for transcriptome analyses were obtained within 24 hours of hospitalization. Multivariate models were constructed to identify virologic and clinical variables predictive of clinical outcomes. Results: We enrolled 253 infants (median age 2.1 [25%-75% interquartile range] months). RSV A infections predominated over RSV B and showed greater genotype variability. RSV A/GA2, A/GA5, and RSV B/BA were the most common genotypes identified. Compared to GA2 or BA, infants with GA5 infections had higher viral loads. GA5 infections were associated with longer hospital stay, and with less activation of interferon and increased overexpression of neutrophil genes. Conclusions: RSV A infections were more frequent than RSV B, and displayed greater variability. GA5 infections were associated with enhanced disease severity and distinct host immune responses.

Rhinovirus Detection in Symptomatic and Asymptomatic Children: Value of Host Transcriptome Analysis.

RATIONALE: Rhinoviruses (RVs) are a major cause of symptomatic respiratory tract infection in all age groups. However, RVs can frequently be detected in asymptomatic individuals. OBJECTIVES: To evaluate the ability of host transcriptional profiling to differentiate between symptomatic RV infection and incidental detection in children. METHODS: Previously healthy children younger than 2 years old (n = 151) were enrolled at four study sites and classified into four clinical groups: RV- healthy control subjects (n = 37), RV+ asymptomatic subjects (n = 14), RV+ outpatients (n = 30), and RV+ inpatients (n = 70). Host responses were analyzed using whole-blood RNA transcriptional profiles. MEASUREMENTS AND MAIN RESULTS: RV infection induced a robust transcriptional signature, which was validated in three independent cohorts and by quantitative real-time polymerase chain reaction with high prediction accuracy. The immune profile of symptomatic RV infection was characterized by overexpression of innate immunity and underexpression of adaptive immunity genes, whereas negligible changes were observed in asymptomatic RV+ subjects. Unsupervised hierarchical clustering identified two main clusters of subjects. The first included 93% of healthy control subjects and 100% of asymptomatic RV+ subjects, and the second comprised 98% of RV+ inpatients and 88% of RV+ outpatients. Genomic scores of healthy control subjects and asymptomatic RV+ children were similar and significantly lower than those of RV+ inpatients and outpatients (P < 0.0001). CONCLUSIONS: Symptomatic RV infection induced a robust and reproducible transcriptional signature, whereas identification of RV in asymptomatic children was not associated with significant systemic transcriptional immune responses. Transcriptional profiling represents a useful tool to discriminate between active infection and incidental virus detection.

Searching for wisdom in oncology care: A scoping review.

OBJECTIVE: The concept of "wisdom" is beginning to emerge in the oncology literature, raising questions concerning: (1) how the concept of wisdom is used in oncology literature; (2) the ways in which wisdom has been a focus of inquiry within oncology care; and (3) how wisdom is characterized when the term is used. METHOD: A scoping review, using Arksey and O'Malley's five-step framework, was undertaken to address these questions. In consultation with oncology reference librarians, "wisdom"- and "oncology"-related search terms were identified, and four electronic databases were searched: CINAHL, SocINDEX, PubMed, and PsychINFO. After removal of duplicates and application of inclusion and exclusion criteria, 58 records were identified and included for analysis. RESULTS: The concept of wisdom was employed with a breadth of meanings, and 58 records were schematized into 7 genres, including: (1) empirical research with wisdom foregrounded as a study focus (n = 2); (2) empirical research articles where "wisdom" appears in the findings (n = 16); (3) a quality-improvement project where wisdom is an embedded concept (n = 1); (4) essays where wisdom is an aspect of the discussion (n = 5); (5) commentary/opinion pieces where wisdom is an aspect of its focus (n = 6); (6) personal stories describing wisdom as something gleaned from lived experience with cancer (n = 2); and (7) everyday/taken-for-granted uses of wisdom (n = 26). SIGNIFICANCE OF RESULTS: The notion of wisdom has a taken-for-granted presence in the published oncology literature and holds promise for future research into patient and clinician wisdom in oncology care. Nonetheless, the terminology is varied and unclear. A scholarly focus on wisdom has not been brought to bear in cancer care to the degree it has in other fields, and research is in the early stages. Various characterizations of wisdom are present. If such a resource as "wisdom" exists, dwelling in human experiences and practices, there may be benefit in recognizing wisdom as informing the epistemologies of practice in oncology care.

Motivations to test for HIV among partners in concordant HIV-negative and HIV-discordant gay male couples.

Previous studies of HIV testing among gay men describe the motivations, facilitators and barriers, behaviors, and demographic characteristics of individuals who test. What little research focuses on HIV testing among gay men in relationships shows that they do not test regularly or, in some cases, at all-their motivations to test have not been investigated. With so little data on HIV testing for this population, and the continued privileging of individually focused approaches, gay men in relationships fall into a blind spot of research and prevention efforts. This study examined motivations to test for HIV using qualitative data from both partners in 20 gay male couples. Analysis revealed that the partners' motivations were either event-related (e.g., participants testing at the beginning of their relationship or HIV-negative participants in an HIV-discordant relationship testing after risky episode with their discordant primary partner) or partner-related (e.g., participants testing in response to a request or suggestion to test from their primary partner or participants testing out of concern for their primary partner's health and well-being). These data provide insight into relationship-oriented motivations to test for HIV for gay men in relationships and, in doing so, evidence their commitment to their primary partner and relationship. These motivations can be leveraged to increase HIV testing among gay men in relationships, a population that tests less often than single gay men, yet, until recently, has been underserved by prevention efforts.

Empiric Antibiotics for Serious Bacterial Infection in Young Infants: Opportunities for Stewardship.

OBJECTIVES: To evaluate the causative agents of serious bacterial infection (SBI) in young infants and the optimal approach to empiric antibiotic therapy for infants with SBI. METHODS: From May 1, 2011, to December 1, 2013, pertinent clinical data were collected on previously well infants 60 days or younger with SBI as defined by a positive bacterial culture from a sterile site. Infants were identified by prospective surveillance of admissions and daily review of microbiology records. RESULTS: Two hundred sixty-five infants with SBI were identified. Mean age was 32 days (SD ±16.6 days). Twenty-nine infants had meningitis, 66 had bacteremia (37 with concomitant urinary tract infection), and 170 had urinary tract infection alone. No methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus sp., or penicillin-resistant Streptococcus pneumoniae were identified. Four extended-spectrum ß-lactamase-producing gram-negative bacilli were seen. Empiric therapy was ampicillin and gentamicin (n = 116, 44%) or third-generation cephalosporin based (n = 149, 56%). Ampicillin and gentamicin, with third-generation cephalosporins reserved for cases where meningitis is suspected, would have provided effective coverage for 98.5% of infants and unnecessarily broad therapy for 4.3%. Third-generation cephalosporins with ampicillin would have been effective for 98.5% of infants and unnecessarily broad for 83.8%. Third-generation cephalosporin monotherapy was less effective than either combination (P < 0.001). Fifty-seven percent of broad spectrum empiric therapy was continued despite culture results allowing de-escalation. CONCLUSIONS: Ampicillin/gentamicin remains an effective empiric regimen for infants 60 days or younger with suspected SBI. Use of a third-generation cephalosporin for suspected meningitis is appropriate, but cerebrospinal fluid must be obtained promptly to guide appropriate therapy.