A Cdk5-derived peptide inhibits Cdk5/p25 activity and improves neurodegenerative phenotypes.

Aberrant activity of cyclin-dependent kinase (Cdk5) has been implicated in various neurodegenerative diseases. This deleterious effect is mediated by pathological cleavage of the Cdk5 activator p35 into the truncated product p25, leading to prolonged Cdk5 activation and altered substrate specificity. Elevated p25 levels have been reported in humans and rodents with neurodegeneration, and the benefit of genetically blocking p25 production has been demonstrated previously in rodent and human neurodegenerative models. Here, we report a 12-amino-acid-long peptide fragment derived from Cdk5 (Cdk5i) that is considerably smaller than existing peptide inhibitors of Cdk5 (P5 and CIP) but shows high binding affinity toward the Cdk5/p25 complex, disrupts the interaction of Cdk5 with p25, and lowers Cdk5/p25 kinase activity. When tagged with a fluorophore (FITC) and the cell-penetrating transactivator of transcription (TAT) sequence, the Cdk5i-FT peptide exhibits cell- and brain-penetrant properties and confers protection against neurodegenerative phenotypes associated with Cdk5 hyperactivity in cell and mouse models of neurodegeneration, highlighting Cdk5i's therapeutic potential.

Conditional deletion of miR-204 and miR-211 in murine retinal pigment epithelium results in retinal degeneration.

MicroRNAs (miRs) are short, evolutionarily conserved noncoding RNAs that canonically downregulate expression of target genes. The miR family composed of miR-204 and miR-211 is among the most highly expressed miRs in the retinal pigment epithelium (RPE) in both mouse and human and also retains high sequence identity. To assess the role of this miR family in the developed mouse eye, we generated two floxed conditional KO mouse lines crossed to the RPE65-ERT2-Cre driver mouse line to perform an RPE-specific conditional KO of this miR family in adult mice. After Cre-mediated deletion, we observed retinal structural changes by optical coherence tomography; dysfunction and loss of photoreceptors by retinal imaging; and retinal inflammation marked by subretinal infiltration of immune cells by imaging and immunostaining. Single-cell RNA sequencing of diseased RPE and retinas showed potential miR-regulated target genes, as well as changes in noncoding RNAs in the RPE, rod photoreceptors, and Müller glia. This work thus highlights the role of miR-204 and miR-211 in maintaining RPE function and how the loss of miRs in the RPE exerts effects on the neural retina, leading to inflammation and retinal degeneration.

Cancer plasticity: Investigating the causes for this agility.

Cancer is not a hard-wired phenomenon but an evolutionary disease. From the onset of carcinogenesis, cancer cells continuously adapt and evolve to satiate their ever-growing proliferation demands. This results in the formation of multiple subtypes of cancer cells with different phenotypes, cellular compositions, and consequently displaying varying degrees of tumorigenic identity and function. This phenomenon is referred to as cancer plasticity, during which the cancer cells exist in a plethora of cellular states having distinct phenotypes. With the advent of modern technologies equipped with enhanced resolution and depth, for example, single-cell RNA-sequencing and advanced computational tools, unbiased cancer profiling at a single-cell resolution are leading the way in understanding cancer cell rewiring both spatially and temporally. In this review, the processes and mechanisms that give rise to cancer plasticity include both intrinsic genetic factors such as epigenetic changes, differential expression due to changes in DNA, RNA, or protein content within the cancer cell, as well as extrinsic environmental factors such as tissue perfusion, extracellular milieu are detailed and their influence on key cancer plasticity hallmarks such as epithelial-mesenchymal transition (EMT) and cancer cell stemness (CSCs) are discussed. Due to therapy evasion and drug resistance, tumor heterogeneity caused by cancer plasticity has major therapeutic ramifications. Hence, it is crucial to comprehend all the cellular and molecular mechanisms that control cellular plasticity. How this process evades therapy, and the therapeutic avenue of targeting cancer plasticity must be diligently investigated.

HBeeID: a molecular tool that identifies honey bee subspecies from different geographic populations.

BACKGROUND: Honey bees are the principal commercial pollinators. Along with other arthropods, they are increasingly under threat from anthropogenic factors such as the incursion of invasive honey bee subspecies, pathogens and parasites. Better tools are needed to identify bee subspecies. Genomic data for economic and ecologically important organisms is increasing, but in its basic form its practical application to address ecological problems is limited. RESULTS: We introduce HBeeID a means to identify honey bees. The tool utilizes a knowledge-based network and diagnostic SNPs identified by discriminant analysis of principle components and hierarchical agglomerative clustering. Tests of HBeeID showed that it identifies African, Americas-Africanized, Asian, and European honey bees with a high degree of certainty even when samples lack the full 272 SNPs of HBeeID. Its prediction capacity decreases with highly admixed samples. CONCLUSION: HBeeID is a high-resolution genomic, SNP based tool, that can be used to identify honey bees and screen species that are invasive. Its flexible design allows for future improvements via sample data additions from other localities.

Leveraging the potential of bacterial lateral gene transfer in boosting the efficacy of an edible probiotic prototype yogurt vaccine for COVID-19.

Administration of coronavirus disease-2019 (COVID-19) vaccines with appropriate booster doses through painful injections under clinical supervision was challenging during the recent COVID-19 pandemic. As an alternative solution, we designed a safer, edible probiotic yogurt vaccine prototype (YoVac) that can be orally consumed by circumventing painful injections and clinical supervision. We hypothesized that YoVac prepared using Lactobacillus carrying an antigen coding gene (donor) can transfer the same to other bacteria (recipients) in the human gut microbiome (hgMb) through lateral gene transfer (LGT) for boosted antigen levels potentially triggering a robust immune response. In this study we confirmed the in vitro LGT efficiency of a plasmid (pRBD-Ampr) containing severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) spike protein-receptor binding domain (RBD) coding gene along with an ampicillin-resistance gene (selection marker) from the probiotic Lactobacillus (donor) cultured from homemade yogurt to E. coli and Helicobacter pylori (recipients). Both the donor and recipient bacteria not only exhibited ampicillin-resistance from pRBD-Ampr but also expressed RBD protein. Furthermore, Lactobacillus isolated from YoVac consistently showed the expression of RBD protein over a period of one month confirming the shelf life of our prototype stored at 4 °C. Taken together, our in vitro results provide a preliminary basis for the potential in vivo transfer of RBD coding gene from YoVac to other bacterial species in the hgMb through LGT and may potentially boost the vaccine dosage by delegating them.

Impact of Diabetes, Drug-Induced Liver Injury, and Sepsis on Outcomes in Metabolic Dysfunction Associated Fatty Liver Disease-Related Acute-on-Chronic Liver Failure.

INTRODUCTION: The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) and its complication, MAFLD-related acute-on-chronic liver failure (MAFLD-ACLF), is rising. Yet, factors determining patient outcomes in MAFLD-ACLF remain understudied. METHODS: Patients with MAFLD-ACLF were recruited from the Asian Pacific Association for the Study of the Liver-ACLF Research Consortium (AARC registry). The diagnosis of MAFLD-ACLF was made when the treating unit had identified the etiology of chronic liver disease as MAFLD (or previous nomenclature such as non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, or non-alcoholic steatohepatitis-cirrhosis). Patients with coexisting other etiologies of chronic liver disease (such as alcohol, hepatitis B virus, hepatitis C virus, etc.) were excluded. Data were randomly split into derivation (n = 258) and validation (n = 111) cohorts at a 70:30 ratio. The primary outcome was 90-day mortality. Only the baseline clinical, laboratory features and severity scores were considered. RESULTS: The derivation group had 258 patients; 60% were male, with a mean age of 53. Diabetes was noted in 27% and hypertension in 29%. The dominant precipitants included viral hepatitis (hepatitis A virus and hepatitis E virus, 32%), drug-induced injury (drug-induced liver injury, 29%), and sepsis (23%). Model for End-Stage Liver Disease-Sodium (MELD-Na) and AARC scores on admission averaged 32 ± 6 and 10.4 ± 1.9. At 90 days, 51% survived. Nonviral precipitant, diabetes, bilirubin, international normalized ratio, and encephalopathy were independent factors influencing mortality. Adding diabetes and precipitant to MELD-Na and AARC scores, the novel MAFLD-MELD-Na score (+12 for diabetes, +12 for nonviral precipitant), and MAFLD-AARC score (+5 for each) were formed. These outperformed the standard scores in both cohorts. DISCUSSION: Almost half of patients with MAFLD-ACLF die within 90 days. Diabetes and nonviral precipitants such as drug-induced liver injury and sepsis lead to adverse outcomes. The new MAFLD-MELD-Na and MAFLD-AARC scores provide reliable 90-day mortality predictions for patients with MAFLD-ACLF.

Determination of the compound class and functional groups in protonated analytes via diagnostic gas-phase ion-molecule reactions.

Diagnostic gas-phase ion-molecule reactions serve as a powerful alternative to collision-activated dissociation for the structural elucidation of analytes when using tandem mass spectrometry. The use of such ion-molecule reactions has been demonstrated to provide a robust tool for the identification of specific functional groups in unknown ionized analytes, differentiation of isomeric ions, and classification of unknown ions into different compound classes. During the past several years, considerable efforts have been dedicated to exploring various reagents and reagent inlet systems for functional-group selective ion-molecule reactions with protonated analytes. This review provides a comprehensive coverage of literature since 2006 on general and predictable functional-group selective ion-molecule reactions of protonated analytes, including simple monofunctional and complex polyfunctional analytes, whose mechanisms have been explored computationally. Detection limits for experiments involving high-performance liquid chromatography coupled with tandem mass spectrometry based on ion-molecule reactions and the application of machine learning to predict diagnostic ion-molecule reactions are also discussed.

Syphilis Diagnosis After a Chlamydia, Gonorrhea, or HIV Diagnosis Among Reproductive-Aged Women in Baltimore, MD.

BACKGROUND: Syphilis incidence is increasing among reproductive-aged women, and previous sexually transmitted infections (STIs) are a risk factor for subsequent STIs. This study aimed to determine syphilis incidence after a chlamydia, gonorrhea, or HIV diagnosis, and identify characteristics associated with higher syphilis incidence rates among reproductive-aged women in 1 mid-Atlantic city. METHODS: A retrospective cohort of 85,113 chlamydia, gonorrhea, and HIV diagnoses occurring between 2009 and 2021 and among women aged 13 to 50 years was constructed using public health surveillance data. Cumulative incidence curves were estimated to examine time to early syphilis (i.e., primary, secondary, or early latent) diagnosis, and multivariable analyses determined incidence rate ratios by age (<25 vs. ≥25 years) and number of prior STI diagnoses (0 vs. ≥1) during the study period, stratified by STI. RESULTS: There were 85,113 reportable STI diagnoses and 646 syphilis diagnoses in the cohort. Approximately 1 of 150 chlamydia, 1 of 100 gonorrhea, and 1 of 50 HIV diagnoses were followed by a syphilis diagnosis within 5 years. Cumulative incidence of syphilis differed significantly by STI diagnosis ( P < 0.001). In multivariable analysis, syphilis incidence rates were higher among women diagnosed with ≥1 (vs. 0) prior STI regardless of STI type ( P < 0.05) and among women ≥25 (vs. <25) years old diagnosed with gonorrhea ( P < 0.05). CONCLUSIONS: There were significant differences in syphilis incidence by prior STI type, number of STIs, and age. Our data support targeted screening for syphilis among women with a history of STIs, parwomen with ≥1 prior STI diagnosis, and older women diagnosed with gonorrhea.

Microbial modulation via cross-fostering prevents the effects of pervasive environmental stressors on microglia and social behavior, but not the dopamine system.

Environmental toxicant exposure, including air pollution, is increasing worldwide. However, toxicant exposures are not equitably distributed. Rather, low-income and minority communities bear the greatest burden, along with higher levels of psychosocial stress. Both air pollution and maternal stress during pregnancy have been linked to neurodevelopmental disorders such as autism, but biological mechanisms and targets for therapeutic intervention remain poorly understood. We demonstrate that combined prenatal exposure to air pollution (diesel exhaust particles, DEP) and maternal stress (MS) in mice induces social behavior deficits only in male offspring, in line with the male bias in autism. These behavioral deficits are accompanied by changes in microglial morphology and gene expression as well as decreased dopamine receptor expression and dopaminergic fiber input in the nucleus accumbens (NAc). Importantly, the gut-brain axis has been implicated in ASD, and both microglia and the dopamine system are sensitive to the composition of the gut microbiome. In line with this, we find that the composition of the gut microbiome and the structure of the intestinal epithelium are significantly shifted in DEP/MS-exposed males. Excitingly, both the DEP/MS-induced social deficits and microglial alterations in males are prevented by shifting the gut microbiome at birth via a cross-fostering procedure. However, while social deficits in DEP/MS males can be reversed by chemogenetic activation of dopamine neurons in the ventral tegmental area, modulation of the gut microbiome does not impact dopamine endpoints. These findings demonstrate male-specific changes in the gut-brain axis following DEP/MS and suggest that the gut microbiome is an important modulator of both social behavior and microglia.

Modeling the atmospheric refractive index structure parameter using macrometeorological observations.

The dynamic fluctuations in the atmospheric refractive index, commonly referred to as optical turbulence, cause phase distortions of the electromagnetic waves propagating through the atmosphere. The consequent scintillations have large implications for free-space optical communication, laser remote sensing, and directed energy applications. The refractive index structure parameter (C n2), quantifying the strength of these fluctuations, is usually estimated using high-frequency micrometeorological measurements, employing sonic anemometer-thermometers or scintillometers. Despite providing highly accurate information, these systems are immensely complex and costly, especially for frequent field applications and remote locations. In this study, we have developed an empirical multinomial model for estimating C n2 using three-year macrometeorological data and validated it against collocated and concurrent micrometeorological measurements, from a tropical semi-arid location. This simpler model would be handy for applications in remote locations having weather station measurements alone.

Clinical analysis of surgical outcome of 89 patients having large cerebral arteriovenous malformations.

OBJECTIVE: The article analyzes the clinical features, morphological characteristics, surgical subtleties and long-term outcome of surgery in 89 cases of 'large' sized AVMs. MATERIALS AND METHODS: During the period 2004 to 2022, 89 cases of 'large' arteriovenous malformations were operated in the neurosurgery departments of the authors. Large AVMs were defined as those that were more than 4 cm on either lateral or antero-posterior view of digital subtraction angiogram. The factors that determined the extent of surgical difficulties included site and eloquence of the area, number of feeding vascular territories and draining veins, degree and rate of flow, presence of flow-related aneurysms, and the physical nature of the arteriovenous malformation. RESULTS: There were 59 males and 30 females and the average age was 32 years. Headache, giddiness and convulsions were the common presenting complaints. Six patients were unconscious after surgery. Of these, five patients died in the immediate post-operative period and one patient gradually recovered. Additionally, seven patients developed unilateral limb weakness that included hemiplegia (4 patients) and hemiparesis (3 patients) following surgery. Clinical follow-up ranged from 6 months to 18 years (average 43 months). All surviving patients are leading normal and essentially symptom free life and have recovered from their symptoms of headache, convulsions and giddiness. CONCLUSIONS: Large AVMs are amenable to 'curative' surgery with 'acceptable' results. The surgery can be challenging and appropriate case selection that is based on the surgeons experience is vital and decisive.

Catharanthus roseus-assisted bio-fabricated zinc oxide nanoparticles for promising antibacterial potential against Klebsiella pneumoniae.

This study emphasized on the synthesis of zinc oxide nanoparticles (ZnO NPs) in an environmentally friendly manner from the extract of Catharanthus roseus leaves and its antibacterial assessment against the pneumonia-causing pathogen Klebsiella pneumoniae. This simple and convenient phytosynthesis approach is found to be beneficial over conventional methods, wherein plants serve as excellent reducing, capping, and stabilizing agents that enables the formation of ZnO NPs without the use of harmful chemicals. The formation of ZnO NPs was confirmed through several characterization techniques such as UV-visible spectroscopy, XRD, FT-IR, SEM, HR-TEM, and EDX. XRD analysis revealed high polycrystallinity with crystallite size of approximately 13 nm. SEM and HR-TEM revealed the hexagonal structure of ZnO NPs with the particle size range of 20-50 nm. The EDX shows the elemental purity without any impurity. Furthermore, the antibacterial efficacy by the technique of disc diffusion exhibited clear inhibition zones in ZnO NPs-treated discs. In addition, 125 µg/mL of ZnO NP concentration showed minimum inhibition by the microbroth dilution method. The potent inhibitory activity was further validated with trypan blue dye exclusion and fluorescence microscopy. Finally, SEM examination confirmed the efficient antibacterial potential of ZnO NPs through disruption of the intact morphology of Klebsiella pneumoniae.

Formulation characterization of lecithin organogel as topical drug delivery system for psoriasis: In-vitro permeation and preclinical evaluation.

Psoriasis is a chronic inflammatory and proliferative skin disease that causes pathological skin changes and has a substantial impact on the quality of patient life. Apremilast was approved by the US Food and Drug Administration as an oral medication for psoriasis and is beneficial in mild to moderate conditions for chronic usage. However, 5%-7% of withdrawals were reported due to severe side effects. To address the issue, a localized drug delivery strategy via the topical route may be a viable approach. However, poor physicochemical properties make it vulnerable to passing through the skin, requiring a specialized drug delivery system to demonstrate its full potential via a topical route like lecithin organogel. The formulation was optimized by screening the suitable lecithin type and non-polar solvents based on the gel formation ability of lecithin and the solubility of apremilast in the solvent. The pseudo-ternary diagram was used to optimize the water content required to form the gel. The optimized gel was found to be shear thinning characterized for rheological parameters, in-vitro diffusion studies, and in-vitro skin distribution studies. Preclinical studies in Imiquimod-induced mice showed a better reduction in severity index, cytokine levels, and epidermal hyperplasia from the lecithin organogel group compared to the apremilast oral administration and marketed standard topical gel group. Based on these results, lecithin organogel can be considered a promising approach to deliver molecules like apremilast by topical route in psoriatic-like conditions.

Fractal Dimension and Lacunarity Analysis in the Dentulous and Edentulous Mandibular Posterior Region Using Cone-beam Computed Tomography: A Cross-sectional Retrospective Study.

AIMS: This cross-sectional retrospective study was conducted to assess the differences in the microarchitecture of the trabecular bone of the posterior mandibular region at dentulous and edentulous sites with the help of fractal dimension (FD) and lacunarity using cone-beam computed tomography (CBCT). MATERIALS AND METHODS: Ninety CBCT scans were analyzed for the purpose of the present study. Inclusion criteria included subjects with unilaterally missing mandibular molars or premolars and an with intact contralateral opposing tooth. The coronal view of the dentulous and edentulous sites was used, and the region of interest (ROI) was selected 2.6 mm below the apex of the tooth present. These images were then transferred to ImageJ Software, and fractal analysis was done using the box-counting method of the FracLac plug-in. A paired samples t-test was performed to compare the means of FD and lacunarity, and a Kendall correlation was performed to check correlations. A p-value less than 0.05 was considered to indicate statistical significance. RESULTS: Statistical analysis revealed that the mean FD of the edentulous side was significantly greater than that of the dentulous side (p-value = 0.011). Additionally, the mean lacunarity of the edentulous side was marginally significantly greater than that of the dentulous side (p-value = 0.089). A significant negative correlation was detected between the FD and lacunarity of the edentulous region (p-value = 0.017), and a marginally significant negative correlation was detected between edentulous lacunarity and dentulous lacunarity (p-value = 0.081). CONCLUSION: The differences in occlusal forces exerted in dentulous and edentulous regions can lead to a change in the trabecular pattern of the bone in these regions. This change in the microarchitecture of bones can be detected by FD and lacunarity, which can further help us assess changes pre- and post-implant. CLINICAL SIGNIFICANCE: The advanced technology, the assessment of microarchitecture of the bone has been made easy, using FD and lacunarity, as done in the present study. This analysis can further aid us in both pre- and post-implant analysis to prevent failure of the implant. How to cite this article: Bhoraskar M, Denny C, Srikant N, et al. Fractal Dimension and Lacunarity Analysis in the Dentulous and Edentulous Mandibular Posterior Region Using Cone-beam Computed Tomography: A Cross-sectional Retrospective Study. J Contemp Dent Pract 2024;25(6):581-587.

Effectiveness of vestibular incision subperiosteal tunnel access technique: A systematic review and meta-analysis.

Vestibular Incision Subperiosteal Tunnel Access (VISTA) root coverage technique has experienced a surge in popularity in recent times. The methodology employed in this study is characterized by its minimally invasive nature, utilizing a single incision. The primary objective of this systematic review was to assess the effectiveness of the VISTA approach for achieving root coverage. The protocol was registered with PROSPERO and included randomized controlled clinical trials where gingival recessions were managed with VISTA technique or its modifications. Among the total of 416 records, a mere 14 studies were initially deemed eligible for consideration. Ultimately, only eight pieces of research were included in the final analysis. There were six studies that exhibited heterogeneity, while two studies showed homogeneity and were therefore included in the meta-analysis. All of the studies considered in the analysis exhibited a moderate to low risk of bias. The majority of the research included in the analysis focused on selective root coverage outcome indicators, while neglecting to incorporate patient-reported outcome measures and patient experienced outcome measures. The VISTA procedure is commonly acknowledged as the most efficacious approach for managing gingival recession. The current literature provides support for the recommendation of the procedure, with evidence of intermediate certainty. The findings of this systematic review indicates that the available data are restricted due to several methodological limitations observed in the included studies. These limitations include, small sample sizes, selective reporting of outcomes, and very short follow-up periods.

Tailoring crops with superior product quality through genome editing: an update.

MAIN CONCLUSION: In this review, using genome editing, the quality trait alterations in important crops have been discussed, along with the challenges encountered to maintain the crop products' quality. The delivery of economic produce with superior quality is as important as high yield since it dictates consumer's acceptance and end use. Improving product quality of various agricultural and horticultural crops is one of the important targets of plant breeders across the globe. Significant achievements have been made in various crops using conventional plant breeding approaches, albeit, at a slower rate. To keep pace with ever-changing consumer tastes and preferences and industry demands, such efforts must be supplemented with biotechnological tools. Fortunately, many of the quality attributes are resultant of well-understood biochemical pathways with characterized genes encoding enzymes at each step. Targeted mutagenesis and transgene transfer have been instrumental in bringing out desired qualitative changes in crops but have suffered from various pitfalls. Genome editing, a technique for methodical and site-specific modification of genes, has revolutionized trait manipulation. With the evolution of versatile and cost effective CRISPR/Cas9 system, genome editing has gained significant traction and is being applied in several crops. The availability of whole genome sequences with the advent of next generation sequencing (NGS) technologies further enhanced the precision of these techniques. CRISPR/Cas9 system has also been utilized for desirable modifications in quality attributes of various crops such as rice, wheat, maize, barley, potato, tomato, etc. The present review summarizes salient findings and achievements of application of genome editing for improving product quality in various crops coupled with pointers for future research endeavors.

Characteristics of Reported Gonorrhea Diagnoses During The COVID-19 Pandemic Compared With Pre-COVID-19 Pandemic, Baltimore City, Maryland.

BACKGROUND: Sexual health service disruptions due to COVID-19 mitigation measures may have decreased gonorrhea screening and biased case-ascertainment toward symptomatic individuals. We assessed changes in reported symptoms and other characteristics among reported gonorrhea cases during pandemic versus prepandemic periods in 1 city with persistent gonorrhea transmission. METHODS: Enhanced surveillance data collected on a random sample of gonorrhea cases reported to the Baltimore City Health Department between March 2018 and September 2021 was used. Logistic regression assessed differences in case characteristics by diagnosis period (during pandemic: March 2020-September 2021; prepandemic: March 2018-September 2019). RESULTS: Analyses included 2750 (1090 during pandemic, 1660 prepandemic) gonorrhea cases, representing 11,904 reported cases. During pandemic versus prepandemic, proportionally fewer cases were reported by sexual health clinics (8.8% vs 23.2%), and more frequently reported by emergency departments/urgent care centers (23.3% vs 11.9%). Adjusting for diagnosing provider, fewer cases who were men with urethral infections (adjusted odds ratio [aOR], 0.65; 95% confidence interval [CI], 0.55-0.77), aged <18 years (aOR, 0.64; 95% CI, 0.47-0.89), and women (aOR, 0.84; 95% CI, 0.71-0.99) were reported, and cases with insurance (aOR, 1.85; 95% CI, 1.40-2.45), living with human immunodeficiency virus (aOR, 1.43; 95% CI, 1.12-1.83), or recent (≤12 months) gonorrhea history (aOR, 1.25; 95% CI, 1.02-1.53) were more frequently reported during pandemic versus prepandemic. Reported symptoms and same-day/empiric treatment did not differ across periods. CONCLUSIONS: We observed no changes in reported symptoms among cases diagnosed during pandemic versus prepandemic. Increased frequency of reported diagnoses who were insured, living with human immunodeficiency virus, or with recent gonorrhea history are suggestive of differences in care access and care-seeking behaviors among populations with high gonorrhea transmission during the pandemic.

Glucose uptake by GLUT1 in photoreceptors is essential for outer segment renewal and rod photoreceptor survival.

Photoreceptors consume glucose supplied by the choriocapillaris to support phototransduction and outer segment (OS) renewal. Reduced glucose supply underlies photoreceptor cell death in inherited retinal degeneration and age-related retinal disease. We have previously shown that restricting glucose transport into the outer retina by conditional deletion of Slc2a1 encoding GLUT1 resulted in photoreceptor loss and impaired OS renewal. However, retinal neurons, glia, and the retinal pigment epithelium play specialized, synergistic roles in metabolite supply and exchange, and the cell-specific map of glucose uptake and utilization in the retina is incomplete. In these studies, we conditionally deleted Slc2a1 in a pan-retinal or rod-specific manner to better understand how glucose is utilized in the retina. Using non-invasive ocular imaging, electroretinography, and histochemical and biochemical analyses we show that genetic deletion of Slc2a1 from retinal neurons and Müller glia results in reduced OS growth and progressive rod but not cone photoreceptor cell death. Rhodopsin levels were severely decreased even at postnatal day 20 when OS length was relatively normal. Arrestin levels were not changed suggesting that glucose uptake is required to synthesize membrane glycoproteins. Rod-specific deletion of Slc2a1 resulted in similar changes in OS length and rod photoreceptor cell death. These studies demonstrate that glucose is an essential carbon source for rod photoreceptor cell OS maintenance and viability.

miR-155 activates cytokine gene expression in Th17 cells by regulating the DNA-binding protein Jarid2 to relieve polycomb-mediated repression.

Specification of the T helper 17 (Th17) cell lineage requires a well-defined set of transcription factors, but how these integrate with posttranscriptional and epigenetic programs to regulate gene expression is poorly understood. Here we found defective Th17 cell cytokine expression in miR-155-deficient CD4+ T cells in vitro and in vivo. Mir155 was bound by Th17 cell transcription factors and was highly expressed during Th17 cell differentiation. miR-155-deficient Th17 and T regulatory (Treg) cells expressed increased amounts of Jarid2, a DNA-binding protein that recruits the Polycomb Repressive Complex 2 (PRC2) to chromatin. PRC2 binding to chromatin and H3K27 histone methylation was increased in miR-155-deficient cells, coinciding with failure to express Il22, Il10, Il9, and Atf3. Defects in Th17 cell cytokine expression and Treg cell homeostasis in the absence of Mir155 could be partially suppressed by Jarid2 deletion. Thus, miR-155 contributes to Th17 cell function by suppressing the inhibitory effects of Jarid2.

Development and use of an infant resuscitation performance tool (Infa-RePT) to improve team performance.

BACKGROUND: Measurement of neonatal team resuscitation performance is critical to identify opportunities for improvement and to target education. An effective tool to measure team performance during infant resuscitations is lacking. METHODS: We developed an in-hospital infant resuscitation performance tool (Infa-RePT) using the modified Delphi method. We employed a QI framework and targeted interventions, including the use of role responsibility checklists, mock codes, and an educational video. We tracked Infa-RePT scores, mock code team attendance, and confidence surveys. Our specific aim was to improve Infa-RePT score from a baseline of 7.4 to <5 (lower is better) over a 26-month period. RESULTS: Twenty-five elements reached >80% consensus as essential components to include on the Infa-RePT. Independent observation showed 86% concordance on checklist items. Simulation (n = 26) and unit-based code (n = 10) Infa-RePT scores showed significant improvement after project start from 7.4 to 4.2 (p < 0.01) with special cause variation noted on control chart analysis. No significant difference was observed between simulations and in-unit codes. Staff confidence self-reports improved over the study period. CONCLUSIONS: Use of a novel scoring tool can help monitor team progress over time and identify areas for improvement. Focused interventions can improve resuscitation team performance. IMPACT: We developed and used a novel, comprehensive measurement tool for team infant resuscitation performance in both simulation and in-unit settings. Using QI methodology, team performance improved after the enhancement of a mock code simulation program. Review of team performance scores can highlight key areas to target interventions and monitor progress over time.