Monolayer-like Exciton Recombination Dynamics of Multilayer MoSe2 Observed by Pump-Probe Microscopy.

Transition metal dichalcogenides (TMDCs) have garnered considerable interest over the past decade as a class of semiconducting layered materials. Most studies on the carrier dynamics in these materials have focused on the monolayer due to its direct bandgap, strong photoluminescence, and strongly bound excitons. However, a comparative understanding of the carrier dynamics in multilayer (e.g., >10 layers) flakes is still absent. Recent computational studies have suggested that excitons in bulk TMDCs are confined to individual layers, leading to room-temperature stable exciton populations. Using this new context, we explore the carrier dynamics in MoSe2 flakes that are between ∼16 and ∼125 layers thick. We assign the kinetics to exciton-exciton annihilation (EEA) and Shockley-Read-Hall recombination of free carriers. Interestingly, the average observed EEA rate constant (0.003 cm2/s) is nearly independent of flake thickness and 2 orders of magnitude smaller than that of an unencapsulated monolayer (0.33 cm2/s) but very similar to values observed in encapsulated monolayers. Thus, we posit that strong intralayer interactions minimize the effect of layer thickness on recombination dynamics, causing the multilayer to behave like the monolayer and exhibit an apparent EEA rate intrinsic to MoSe2.

Surgical outcomes and revision rates for velopharyngeal insufficiency (VPI) in syndromic and non-syndromic children: A systematic review and meta-analysis.

PURPOSE: To evaluate pre- and post-operative resonance, surgical technique, revision rate, and revision indication among syndromic and non-syndromic children with velopharyngeal insufficiency (VPI). MATERIALS AND METHODS: A systematic review was conducted through July 2022. Children surgically treated for VPI were included. A meta-analysis of single means, proportions, comparison of proportions, and mean differences with 95 % confidence interval [CI] was conducted. RESULTS: Twenty-three articles (n = 1437) were included in the analysis. The most common surgery was Sphincter Pharyngoplasty (SP), 62.6 % [31.3-88.9] for syndromic and 76.3 % [37.5-98.9] for non-syndromic children. Among all surgical techniques, for syndromic and non-syndromic children, 54.8 % [30.9-77.5] and 73.9 % [61.3-84.6] obtained normal resonance post-operatively, respectively. Syndromic patients obtained normal resonance post-operatively in 83.3 % [57.7-96.6] of Combined Furlow Palatoplasty and Sphincter Pharyngoplasty (CPSP), 72.6 % [54.5-87.5] of Pharyngeal Flap (PF), and 45.1 % [13.2-79.8] of Sphincter Pharyngoplasty (SP) surgeries. Non-syndromic patients obtained normal resonance post-operatively in 79.2 % [66.4-88.8] of PF and 75.2 % [61.8-86.5] of SP surgeries. The revision rate for syndromic and non-syndromic patients was 19.9 % [15.0-25.6] and 11.3 % [5.8-18.3], respectively. The difference was statistically significant, 8.6 % [2.9-15.0, p = 0.003]. Syndromic patients who underwent PF were least likely to undergo revision surgery as compared to SP and CPSP, 7.7 % [2.3-17.9] vs. 23.7 % [15.5-33.1] and 15.3 % [2.8-40.7], respectively. CONCLUSIONS: Syndromic children had higher revision rates and were significantly less likely to obtain normal resonance following primary surgery than non-syndromic patients. Among syndromic children, PF and CPSP have been shown to improve resonance and reduce revision rates more so than SP alone.

Placebo effect in randomized controlled trials for Meniere's disease: A meta-analysis.

PURPOSE: Meniere's Disease is a condition known for its recurrent vertigo, fluctuating sensorineural hearing loss, aural fullness, and tinnitus. Previous studies have demonstrated significant influence of placebo treatments. Our objective was to quantify the magnitude of the placebo effect in randomized controlled trials for Meniere's Disease. MATERIALS AND METHODS: A systematic review was performed by searching PubMed, SCOPUS, CINAHL, and Cochrane databases from inception through September 27, 2022. Data extraction, quality rating, and risk of bias assessment were performed by two independent reviewers. A meta-analysis of mean differences with 95 % confidence interval, weighted summary proportions, and proportion differences were calculated using random and fixed effects models. RESULTS: A total of 15 studies (N = 892) were included in the review. Significant improvement was seen in the functional level scores of the pooled placebo groups, with a mean difference of -0.6 points, (95%CI: -1.2 to -0.1). There was no difference in pure tone audiometry, speech discrimination score, or vertigo frequency at 1 and 3 months for the placebo group. Patient-reported vertigo episodes were improved in 52.5 % (95%CI: 39.2 to 65.5) of the placebo group and was significantly less than the pooled experimental group (90.1 %, 95%CI: 39.2 to 65.5, p < 0.001). CONCLUSIONS: The placebo effect in Meniere's Disease trials is associated with some symptomatic improvement in subjective outcomes, such as patient reported vertigo episodes. However, the clinical significance is questionable across other outcomes measures, especially when analyzing objective data. The extent and strength of the placebo effect continues to be a hurdle in the search for better treatment options.

Machine Learning To Stratify Methicillin-Resistant Staphylococcus aureus Risk among Hospitalized Patients with Community-Acquired Pneumonia.

Methicillin-resistant Staphylococcus aureus (MRSA) is an uncommon but serious cause of community-acquired pneumonia (CAP). A lack of validated MRSA CAP risk factors can result in overuse of empirical broad-spectrum antibiotics. We sought to develop robust models predicting the risk of MRSA CAP using machine learning using a population-based sample of hospitalized patients with CAP admitted to either a tertiary academic center or a community teaching hospital. Data were evaluated using a machine learning approach. Cases were CAP patients with MRSA isolated from blood or respiratory cultures within 72 h of admission; controls did not have MRSA CAP. The Classification Tree Analysis algorithm was used for model development. Model predictions were evaluated in sensitivity analyses. A total of 21 of 1,823 patients (1.2%) developed MRSA within 72 h of admission. MRSA risk was higher among patients admitted to the intensive care unit (ICU) in the first 24 h who required mechanical ventilation than among ICU patients who did not require ventilatory support (odds ratio [OR], 8.3; 95% confidence interval [CI], 2.4 to 32). MRSA risk was lower among patients admitted to ward units than among those admitted to the ICU (OR, 0.21; 95% CI, 0.07 to 0.56) and lower among ICU patients without a history of antibiotic use in the last 90 days than among ICU patients with antibiotic use in the last 90 days (OR, 0.03; 95% CI, 0.002 to 0.59). The final machine learning model was highly accurate (receiver operating characteristic [ROC] area = 0.775) in training and jackknife validity analyses. We identified a relatively simple machine learning model that predicted MRSA risk in hospitalized patients with CAP within 72 h postadmission.

HPV Knowledge Retention and Concurrent Increase in Vaccination Rates 1.5 Years After a Novel HPV Workshop in Medical School.

Comprehensive education regarding human papillomavirus (HPV) pathogenesis, vaccination, and patient counseling are not routinely included in the medical school curriculum; consequently, student and provider knowledge, especially concerning head and neck pathology, remains low. The objective of this study was to demonstrate long-term retention of HPV knowledge and positive attitudes towards HPV vaccination after attending our novel HPV workshop, with a focus on knowledge of oropharyngeal cancer. A follow-up survey was administered to medical students 1.5 years after the initial completion of the workshop. HPV vaccination records from the student-led clinic were collected from the immunization information system. Awareness that HPV causes oropharyngeal cancer was present in 33% of medical students pre-curriculum; immediate and long-term post-curricular awareness of this association remained at 90% or higher (p < 0.0001). Comfort with HPV counseling, having enough information to recommend the vaccine, and knowledge of HPV malignancies, symptoms, transmission, and vaccination schedule remained persistently elevated over pre-curriculum scores (p < 0.05). Long-term knowledge scores were also higher than a control group of medical students at the same stage of training who had never participated in the workshop (p < 0.05). HPV vaccination rates at the medical school's student-run clinic also increased after the curriculum, from an average of 1.89 HPV vaccines given per clinic to 3.55 (p = 0.001). This study demonstrates that knowledge and positive attitudes were maintained 1.5 years after participating in this HPV curriculum during students' preclinical years of medical school. Additionally, an increase in HPV vaccination rates occurred at a student-led clinic, indicating a positive clinical impact on the curriculum.

Innate Immune System Activation, Inflammation and Corneal Wound Healing.

Corneal wounds resulting from injury, surgeries, or other intrusions not only cause pain, but also can predispose an individual to infection. While some inflammation may be beneficial to protect against microbial infection of wounds, the inflammatory process, if excessive, may delay corneal wound healing. An examination of the literature on the effect of inflammation on corneal wound healing suggests that manipulations that result in reductions in severe or chronic inflammation lead to better outcomes in terms of corneal clarity, thickness, and healing. However, some acute inflammation is necessary to allow efficient bacterial and fungal clearance and prevent corneal infection. This inflammation can be triggered by microbial components that activate the innate immune system through toll-like receptor (TLR) pathways. In particular, TLR2 and TLR4 activation leads to pro-inflammatory nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) activation. Similarly, endogenous molecules released from disrupted cells, known as damage-associated molecular patterns (DAMPs), can also activate TLR2, TLR4 and NFκB, with the resultant inflammation worsening the outcome of corneal wound healing. In sterile keratitis without infection, inflammation can occur though TLRs to impact corneal wound healing and reduce corneal transparency. This review demonstrates the need for acute inflammation to prevent pathogenic infiltration, while supporting the idea that a reduction in chronic and/or excessive inflammation will allow for improved wound healing.

Characterizing Risk Factors for Clostridioides difficile Infection among Hospitalized Patients with Community-Acquired Pneumonia.

Hospitalized patients with community-acquired pneumonia (CAP) are at risk of developing Clostridioides difficile infection (CDI). We developed and tested clinical decision rules for identifying CDI risk in this patient population. The study was a single-center retrospective, case-control analysis of hospitalized adult patients empirically treated for CAP between 1 January 2014 and 3 March 2018. Differences between cases (CDI diagnosed within 180 days following admission) and controls (no test result indicating CDI during the study period) with respect to prehospitalization variables were modeled to generate propensity scores. Postadmission variables were used to predict case status on each postadmission day where (i) ≥1 additional case was identified and (ii) each model stratum contained ≥15 subjects. Models were developed and tested using optimal discriminant analysis and classification tree analysis. Forty-four cases and 181 controls were included. The median time to diagnosis was 50 days postadmission. After weighting, three models were identified (20, 117, and 165 days postadmission). The day 20 model yielded the greatest (weighted [w]) accuracy (weighted area under the receiver operating characteristic curve [wROC area] = 0.826) and the highest chance-corrected accuracy (weighted effect strength for sensitivity [wESS] = 65.3). Having a positive culture (odds, 1:4; P = 0.001), receipt of ceftriaxone plus azithromycin for a defined infection (odds, 3:5; P = 0.006), and continuation of empirical broad-spectrum antibiotics with activity against P. aeruginosa when no pathogen was identified (odds, 1:8; P = 0.013) were associated with CDI on day 20. Three models were identified that accurately predicted CDI in hospitalized patients treated for CAP. Antibiotic use increased the risk of CDI in all models, underscoring the importance of antibiotic stewardship.

Participation and engagement of a rural community in Ciclovía: progressing from research intervention to community adoption.

BACKGROUND: Open streets events, where roads are temporarily closed to motorized vehicles, can provide safe spaces for physical activity (PA) and become sustainable community infrastructure. Since 2016, we have collaborated with a rural community to implement an open streets event, named ciclovía. In 2019, ciclovía was adopted as a community-wide program. This paper describes the process of building and progressing a ciclovía from a research intervention to a community-adopted program and participation of a rural community in ciclovía. METHODS: We used community-based participatory research to foster bidirectional learning on how to optimize the content and implementation of ciclovía to be feasible and acceptable for rural communities. The community-academic partnership focused on: 1) understanding the science of ciclovía; 2) learning the implementation process; 3) creating tools to facilitate planning, implementation, and evaluation of ciclovía; and 4) developing transition steps from a research intervention to a community-adopted program. RESULTS: The progression of the research intervention to community adoption spanned 2 years. First, the partnership met quarterly to discuss the science of ciclovía, its utility, and its adaptation for rural communities. Second, the partnership studied processes that facilitated ciclovía implementation. Third, the partnership created the ciclovía planning guide and tools for communities to establish their own ciclovía. The guide included forming a planning committee, setting meeting and communication plans, marketing and promotion, and selecting evaluation tools. Fourth, the transition steps from research intervention to community adoption included creating roles and responsibilities, implementing ciclovía using the planning guide, and convening listening sessions for improvement on implementation. Community attendance at ciclovía doubled from 189 individuals (126 children and 63 adults) when it was a research intervention to 394 individuals (277 children and 117 adults) when it was a community program. CONCLUSIONS: The progression from a research intervention to a community-adopted program encompasses multiple steps that involve bidirectional learning and partnership with the community. Lessons learned from this study are integrated into a disseminatable ciclovía planning guide.

Home Birth in the Era of COVID-19: Counseling and Preparation for Pregnant Persons Living with HIV.

With the coronavirus disease 2019 (COVID-19) pandemic in the United States, a majority of states have instituted "shelter-in-place" policies effectively quarantining individuals-including pregnant persons-in their homes. Given the concern for COVID-19 acquisition in health care settings, pregnant persons with high-risk pregnancies-such as persons living with HIV (PLHIV)-are increasingly investigating the option of a home birth. Although we strongly recommend hospital birth for PLHIV, we discuss our experience and recommendations for counseling and preparation of pregnant PLHIV who may be considering home birth or at risk for unintentional home birth due to the pandemic. We also discuss issues associated with implementing a risk mitigation strategy involving high-risk births occurring at home during a pandemic. KEY POINTS: · Coronavirus disease 2019 pandemic has increased interest in home birth.. · Women living with HIV are pursuing home birth.. · Safe planning is paramount for women living with HIV desiring home birth, despite recommending against the practice..

Cutaneous manifestations of Campylobacter jejuni infection: A case report and review of the literature.

A 51 year old man with active follicular lymphoma presented with several days of erythematous skin nodules on all extremities two weeks after a self-limited diarrheal illness. All serum immunoglobulin levels were found to be low. Blood cultures grew Campylobacter jejuni. The patient was given one week of azithromycin with complete resolution of his skin nodules. The literature of skin manifestations seen in active Campylobacter jejuni infection are reviewed. The majority of cases occur in immunocompromised hosts, many with low or no serum immunoglobulin levels. Postulated mechanisms include a lack of secretory IgA in intestinal mucosa predisposing susceptible patients to translocated enteric pathogens however the precise pathogenesis underlying cutaneous manifestations are unknown.

Going for the Gold: A Description of the Centers of Excellence Designation by the Infectious Diseases Society of America.

Antimicrobial stewardship programs (ASPs) are recommended by the Centers for Disease Control and Prevention and World Health Organization and mandated by the Joint Commission to curb antimicrobial resistance. However, <50% of institutions have optimal ASPs in place. Building on its experience of antimicrobial stewardship (AMS) advocacy, the Infectious Diseases Society of America (IDSA) developed the AMS Centers of Excellence (CoE) program, which will serve as a conduit to share best practices and highlight the standards for other hospitals to achieve in order to advance the field of AMS. A designation of CoE signifies that these institutions deliver high-quality care consistently, serve as the "gold" standard for executing novel AMS principles, and demonstrate commitment to their ASP. Here, we describe the process and purpose of designating institutions as AMS CoEs, provide awareness to clinicians on opportunities available through IDSA with this CoE designation, and discuss the evolution of the program.

Understanding the Components, Calculation, and Impact of Monthly and Seasonal Variation of the Standardized Antimicrobial Utilization Ratio (SAAR).

This study sought to characterize the impact of 3 types of variation on the Standardized Antimicrobial Administration Ratio (SAAR) utilizing local National Healthcare Safety Network (NHSN) data. SAAR and antimicrobial days per 1,000 days present (AD/1000DP) were compiled monthly for Northwestern Memorial Hospital from 2014 to 2016. Antimicrobial consumption was aggregated into agent categories (via NHSN criteria). Month-to-month changes in SAAR and AD/1000DP were evaluated. Azithromycin and oseltamivir AD/1000DP from 2012 through 2017 were explored for seasonal variation. A sensitivity analysis was performed to explore the effect of seasonality and altered consumption at other hypothetical hospitals on the SAAR. Across agent categories for both the intensive care unit (n = 4) and general wards (n = 4), the average matched-month percent change in AD/1000DP was correlated with the corresponding change in SAAR (coefficient of determination of 0.99). The monthly mean ± standard deviation (SD) AD/1000DP was 235 (range, 47.2 to 661.5), and the mean ± SD SAAR was 1.09 ± 0.26 (range, 0.79 to 1.09) across the NHSN agent categories. Five seasons exhibited seasonal variation in AD/1000DP for azithromycin with a mean percent change of 26.76% (range, 22.27 to 30.69). Eight seasons exhibited seasonal variation in AD/1000DP for oseltamivir with a mean percent change of 129.1% (range, 32.01 to 352.74). The sensitivity analyses confirm that antimicrobial usage at comparator hospitals does not impact the local SAAR, and seasonal variation of antibiotics has the potential to impact SAAR. Month-to-month changes in the SAAR mirror monthly changes in an institution's AD/1000DP. Seasonal variation is an important variable for future SAAR consideration, and the variable antibiotic use at peer hospitals is not currently captured by the SAAR methodology.

Evaluation of the impact of the Accelerate Pheno™ system on time to result for differing antimicrobial stewardship intervention models in patients with gram-negative bloodstream infections.

BACKGROUND: Initiating early effective antimicrobial therapy is the most important intervention demonstrated to decrease mortality in patients with gram-negative bacteremia with sepsis. Rapid MIC-based susceptibility results make it possible to optimize antimicrobial use through both escalation and de-escalation. METHOD: We prospectively evaluated the performance of the Accelerate Pheno™ system (AXDX) for identification and susceptibility testing of gram-negative species and compared the time to result between AXDX and routine standard of care (SOC) using 82 patient samples and 18 challenge organisms with various confirmed resistance mechanisms. The potential impact of AXDX on time to antimicrobial optimization was investigated with various simulated antimicrobial stewardship (ASTEW) intervention models. RESULTS: The overall positive and negative percent agreement of AXDX for identification were 100 and 99.9%, respectively. Compared to VITEK® 2, the overall essential agreement was 96.1% and categorical agreement was 95.4%. No very major or major errors were detected. AXDX reduced the time to identification by an average of 11.8 h and time to susceptibility by an average of 36.7 h. In 27 patients evaluated for potential clinical impact of AXDX on antimicrobial optimization, 18 (67%) patients could potentially have had therapy optimized sooner with an average of 18.1 h reduction in time to optimal therapy. CONCLUSION: Utilization of AXDX coupled with simulated ASTEW intervention notification substantially shortened the time to potential antimicrobial optimization in this cohort of patients with gram-negative bacteremia. This improvement in time occurred when ASTEW support was limited to an 8-h coverage model.

Understanding HIV-Related Pill Aversion as a Distinct Barrier to Medication Adherence.

Pill aversion, defined as difficulty swallowing pills without identifiable medical cause, is a poorly characterized barrier to sustained viral suppression for many HIV-infected persons. We aimed to quantify the frequency of self-reported pill aversion, characterize its symptoms, and measure the association between self-reported pill aversion and missing antiretroviral doses. This is a prospective, observational, exploratory survey study of English-speaking persons living with HIV (PLHIV) at a single urban tertiary outpatient clinic. Participants completed anonymous questionnaires about their experiences of swallowing antiretroviral pills. The primary outcome was skipping pills due to pill aversion symptoms. Of 384 participants, a quarter (25.5%) skipped pills due to pill aversion symptoms. Younger age, being Non-Hispanic Black or Hispanic, not being married or partnered, having public insurance, not being employed, having less than a college education, and having a mental health diagnosis were associated with skipping pills due to pill aversion. On multivariable regression analyses, PLHIV who skipped pills were more likely to report symptoms of gagging, nausea at the time of swallowing, and heavy feeling in the stomach, as well as being bothered by the taste, smell, and size of the pills. PLHIV who skipped pills were also more likely to report negative and fear-based emotions about pill-taking than PLHIV who did not skip pills due to pill aversion. HIV-related pill aversion may represent a significant and frequent barrier to adherence in an adult HIV population.

Measuring the impact of varying denominator definitions on standardized antibiotic consumption rates: implications for antimicrobial stewardship programmes.

Objectives: To quantify the impact of varying the at-risk days definition on the overall report of at-risk days and on the calculated standardized consumption rates (SCRs) for piperacillin/tazobactam, amikacin, daptomycin and vancomycin. Methods: Data were evaluated for two system hospitals, an 894 bed academic centre and a 114 bed community hospital. Aggregate inpatient antibiotic administration and occupancy data were extracted from electronic databases at the facility-wide level. Occupancy data were reported from admission-discharge-transfer systems. At-risk days were defined as hospital days present (DP), patient days (PD), persons present (PP) and billing days (BD). Inpatient antimicrobial days of therapy (DOT) across four major antimicrobial agents were used to calculate facility-wide SCRs using each denominator and were evaluated by least-squares regression and R2 values. Results: Within the 894 bed academic hospital, the average monthly facility-wide days were 28 424, 22 198, 15 957 and 14 789 by the DP, PP, PD and BD definitions, respectively. Within the 114 bed community hospital, the average monthly facility-wide days were 5175, 3523 and 2816 by the DP, PP and PD definitions, respectively. Strong concordance was observed between facility-wide SCRs using the DP and PP definitions in both the academic (R2 = 0.99, y = 0.78x - 0.001) and community (R2 = 0.99, y = 0.68x - 0.03) centres across all four inpatient antibiotics evaluated. In an analysis of piperacillin/tazobactam SCRs, rates were over-predicted by 28%-93% at the facility-wide level across centres using alternative denominators. Conclusions: We found that data source and definitions of at-risk denominator days meaningfully impact antibiotic SCRs. Centres should carefully consider these potential sources of variation when setting consumption benchmarks and internally evaluating use.

Telemedicine in the Management of Type 1 Diabetes.

BACKGROUND: Veterans with type 1 diabetes who live in rural Alabama and Georgia face barriers to receiving specialty diabetes care because of a lack of endocrinologists in the Central Alabama Veterans Health Care System. Telemedicine is a promising solution to help increase access to needed health care. We evaluated telemedicine's effectiveness in delivering endocrinology care from Atlanta-based endocrinologists. METHODS: We conducted a retrospective chart review of patients who were enrolled in the Atlanta VAMC Endocrinology Telehealth Clinic from June 2014 to October 2016. Outcomes of interest were hemoglobin A1c levels, changes in glycemic control, time savings for patients, cost savings for the US Veterans Health Administration, appointment adherence rates, and patient satisfaction with telehealth. RESULTS: Thirty-two patients with type 1 diabetes received telehealth care and in general received the recommended processes of diabetes care. Patients trended toward a decrease in mean hemoglobin A1c and glucose variability and a nonsignificant increase in hypoglycemic episodes. Patients saved 78 minutes of travel time (one way), and the VA saved $72.94 in travel reimbursements per patient visit. Patients adhered to 88% of scheduled telehealth appointments on average, and 100% of surveyed patients stated they would recommend telehealth to other veterans. CONCLUSIONS: Specialty diabetes care delivered via telemedicine was safe and was associated with time savings, cost savings, high appointment adherence rates, and high patient satisfaction. Our findings support growing evidence that telemedicine is an effective alternative method of health care delivery.

Switch to atovaquone and subsequent re-challenge with trimethoprim-sulfamethoxazole for Pneumocystis prophylaxis in a kidney transplant population.

Kidney transplant recipients who are switched to atovaquone (ATO) from trimethoprim-sulfamethoxazole (TMP/SMX) for Pneumocystis jirovecii pneumonia (PJP) prophylaxis because of adverse events or complications may miss opportunities to be re-challenged with TMP/SMX, the first-line agent. This single-site, retrospective study assessed kidney transplant recipients for documented reasons for switching from TMP/SMX to alternate PJP prophylaxis and outcomes of TMP/SMX re-challenge. Out of 166 patients, 155 initially received TMP/SMX; of these, 31 were switched to ATO for various reasons. Fourteen patients receiving ATO were re-challenged with TMP/SMX; all were successfully re-initiated on TMP/SMX therapy. Most patients switched to ATO post kidney transplant secondary to non-hypersensitivity reasons should be re-challenged with TMP/SMX because of the advantages it provides over other agents.

The assembly of a GTPase-kinase signalling complex by a bacterial catalytic scaffold.

The fidelity and specificity of information flow within a cell is controlled by scaffolding proteins that assemble and link enzymes into signalling circuits. These circuits can be inhibited by bacterial effector proteins that post-translationally modify individual pathway components. However, there is emerging evidence that pathogens directly organize higher-order signalling networks through enzyme scaffolding, and the identity of the effectors and their mechanisms of action are poorly understood. Here we identify the enterohaemorrhagic Escherichia coli O157:H7 type III effector EspG as a regulator of endomembrane trafficking using a functional screen, and report ADP-ribosylation factor (ARF) GTPases and p21-activated kinases (PAKs) as its relevant host substrates. The 2.5 Å crystal structure of EspG in complex with ARF6 shows how EspG blocks GTPase-activating-protein-assisted GTP hydrolysis, revealing a potent mechanism of GTPase signalling inhibition at organelle membranes. In addition, the 2.8 Å crystal structure of EspG in complex with the autoinhibitory Iα3-helix of PAK2 defines a previously unknown catalytic site in EspG and provides an allosteric mechanism of kinase activation by a bacterial effector. Unexpectedly, ARF and PAKs are organized on adjacent surfaces of EspG, indicating its role as a 'catalytic scaffold' that effectively reprograms cellular events through the functional assembly of GTPase-kinase signalling complex.

Investigating the Extremes of Antibiotic Use with an Epidemiologic Framework.

Benchmarks for judicious use of antimicrobials are needed. Metrics such as defined daily doses (DDDs) and days of therapy (DOTs) quantify antimicrobial consumption. However, benchmarking with these metrics is complicated by interhospital variability. Thus, it is important for each hospital to monitor its own temporal consumption trends. Time series analyses allow trends to be detected; however, many of these methods are complex. We present simple regressive methods and caveats in using them to define potential antibiotic over- and underutilizations.

Is maternal disclosure of HIV serostatus associated with a reduced risk of postpartum depression?

BACKGROUND: Patients with chronic diseases that include HIV infection are at increased risk of experiencing postpartum depression. In addition, social isolation has been associated with depression among women with HIV. Yet, it is unclear whether disclosure of HIV serostatus before the birth is associated with the risk of postpartum depression. OBJECTIVE: The purpose of this study was to determine whether maternal disclosure of her positive HIV serostatus before the delivery is associated with the risk of early postpartum depression. STUDY DESIGN: In this retrospective cohort study, women who received obstetric care in a specialty perinatal HIV clinic (2007-2014) were stratified by whether, before the delivery, they had disclosed their HIV serostatus to (1) their sexual partner(s) or (2) at least 1 family member aside from sexual partner(s). Postpartum depression was identified initially by a positive result on a validated depression screening tool (Patient Health Questionnaire-9 or Edinburgh Postnatal Depression Scale) at the 6-week postpartum visit and then confirmed by evaluation with a mental health professional. Postpartum depression rates were compared by disclosure status. Multivariable logistic regression was performed to identify whether disclosure to either sexual partner(s) or family members remained associated independently with postpartum depression after we controlled for potential confounders that included antenatal mental health disorders. RESULTS: Of the 215 women who received perinatal HIV care in this center and who had a documented disclosure status, 149 women (71.3%) had disclosed to their sexual partner(s), and 78 women (42.9%) had disclosed to at least 1 family member who was not a sexual partner. Although disclosure to sexual partner(s) was associated with a reduction in the proportion of women with postpartum depression (15.6% vs 25.5%), this difference did not reach statistical significance (P = .126) and remained statistically insignificant after we controlled for potential confounders (adjusted odds ratio, 0.47; 95% confidence interval, 0.15-1.41). In contrast, disclosure to family member(s) was associated with a decreased prevalence of postpartum depression (11.4% vs 24.7%; P = .03), and this difference persisted in multivariable regression (adjusted odds ratio, 0.35; 95% confidence interval, 0.13-0.95). CONCLUSION: In this cohort, maternal disclosure of HIV serostatus to family members (other than sexual partner[s]) was associated independently with a reduction in postpartum depression by more than one-half. Disclosure of HIV serostatus to a family member may be a marker for psychosocial well-being and enhanced support that affords protection against postpartum depression.