Risk factors for curable sexually transmitted infections among youth: findings from the STICH population survey in Zimbabwe.

OBJECTIVES: Youth are at high risk of sexually transmitted infections (STIs) in Africa. We aimed to determine the risk factors for curable STIs in youth in Zimbabwe. METHODS: A population-based survey was conducted among randomly selected 18-24 year-olds in 16 communities across two provinces in Zimbabwe to ascertain outcomes for a cluster randomised trial investigating the impact of community-based STI screening for youth on population prevalence of STIs. Participants underwent an interviewer-administered questionnaire, HIV testing and screening for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV). Risk factors for curable STIs were explored through multivariable logistic regression. RESULTS: Of the 5601 participants, 62.5% (n=3500) were female, and the median age was 20 (IQR 19-22) years. HIV prevalence was 6.3% (351/5556), and 55.4% (1939/3501) reported condomless sex at last intercourse. Only 7.2% (401/5599) reported STI symptoms, but CT/NG/TV prevalence was 19.8% (1107/5601). On multivariable analysis, factors associated with STI diagnosis included being aged 21-24 years (adjusted OR (aOR) 1.37, 95% CI 1.17 to 1.61); female sex (aOR 2.11, 95% CI 1.76 to 2.53); being unemployed/informally employed (compared with in education/formal employment) (aOR 1.35, 95% CI 1.13 to 1.61); increasing number of sexual partners in the preceding 12 months (one partner: aOR 2.23, 95% CI 1.73 to 2.88; two partners: aOR 2.39, 95% CI 1.69 to 3.39); living with HIV (aOR 1.44, 95% CI 1.07 to 1.94); and previous attempted suicide (aOR 1.58, 95% CI 1.08 to 2.32). CONCLUSIONS: The prevalence of STIs among youth in Zimbabwe is high, particularly among those with HIV. In addition to moving away from syndromic STI management and strengthening implementation of existing prevention tools, there is a need for a more holistic focus on broader risk factors such as mental health and employment opportunities, and of integration of HIV and STI programming. TRIAL REGISTRATION NUMBER: ISRCTN15013425, NCT03719521.

Helicene Appended Benzothiadiazoles as Chiral Emitters.

A homologous series of 4,7-bis(aryl) substituted benzothiadiazole (BTD) compounds, containing the helicenic derivatives bis([4]helicene), bis([5]helicene) and bis([6]helicene), have been prepared upon a double Suzuki coupling between 3,6-bis(pinacolyl-borane)-BTD and the corresponding bromo-aryl precursors. The single crystal X-ray structure of the bis([4]helicene) compound shows the existence of both helicities (M) and (P) on the same molecule. All the compounds of the series are highly emissive in solution, with quantum yields of the emission ranging from 50 to 91 %. The enantiopure compounds (M,M) and (P,P) for the BTD-bis([6]helicene) have been prepared from the corresponding enantiopure 2-bromo-[6]helicene precursors. Their chiroptical properties have been investigated in correlation with density functional theory (DFT) calculations, which allowed to confidently assign the absolute configuration of the helicene arms and to characterize the different electronic transitions, including the low energy charge transfer excitation from helicenes to BTD. The enantiomerically pure fluorophores (M,M)- and (P,P)-BTD-bis([6]helicene), which exist in solution as two main conformers, according to the DFT calculations, show CPL activity in solution, with glum factors of ≈1.7×10-3 at λem=525 nm, and also in the solid state, with glum factors of ≈1.2×10-3 in spite of the strong decrease of the quantum efficiency.

The Triplanar Hallux Abducto Valgus Classification System: Is it Valid?

Historically, 2-dimensional radiographic study techniques have been used to classify deformity and guide treatment of hallux valgus deformities in the transverse plane. Recently, a triplanar hallux abducto valgus classification system was proposed. The key elements of this classification system are the pathologic alignments in 3 anatomic planes. The triplanar hallux abducto valgus classification system is intended to clarify the deformity and apply a triplanar anatomic algorithm for treatment. To our knowledge, this classification system has not been validated. Our objective was to assess reliability of the triplanar hallux valgus classification system. Patients with hallux abducto valgus were identified from a foot and ankle registry. Digital radiographs were assembled in a digital slide presentation. The eligibility criteria required complete radiographic studies and represented varying degrees of hallux abducto valgus. The reviewers included 3 board-certified, fellowship-trained orthopedic foot and ankle surgeons. Each reviewer independently classified the hallux abducto valgus deformity for a total of 75 observations. After an 8-week washout period, the order of the hallux abducto valgus cases was randomized in the digital slide presentation and redistributed to the reviewers. The average kappa value from 3 readers was 0.241 with 95% CI (0.093-0.374), indicating a fair agreement. The inter-reader agreement was 0.046 with 95% CI (-0.041 to 0.112), showing poor agreement between readers. Our results indicate the triplanar hallux abducto valgus is not a reliable classification system. While this is the first known triplanar hallux abducto valgus classification system, it lacks prognostic value and reliability.

Managing cybersecurity risk in healthcare settings.

Cybersecurity attacks have been steadily increasing in the healthcare sector over the past decade. Health data is a valuable source of reliable and permanent personal information making it an attractive target. Institutions that have faced limited cybersecurity funding must now augment their approach to combat this threat. The Internet of Things (IoT) refers to the connection of physical operational devices to digital networks allowing for communication between devices. In the healthcare setting, this includes patient monitoring, diagnostics, and even robotic surgery devices. This increased connectivity increases the importance of agile and robust cybersecurity measures. A progressive approach must involve collaboration between information technology, clinical, and administrative leaders to be successful. Adequate protection of patient data and the integrity of digital infrastructure must be a priority mandate at the enterprise level.

Highly Stereospecific On-Surface Dimerization into Bishelicenes: Topochemical Ullmann Coupling of Bromohelicene on Au(111).

The on-surface dimerization into bis(hexahelicene) on a gold(111) surface has been studied by means of scanning tunneling microscopy and time-of-flight secondary mass spectrometry. C-C Ullmann coupling of (rac)-2-bromo-hexahelicene leads to formation of the (M,M)- and (P,P)-diastereomers of 2,2'-bis(hexahelicene), whilst formation of the (M,P)-diastereomer is not observed. Upon cooling, the bis(hexahelicene) aggregates into an ordered two-dimensional lattice with partly randomly distributed enantiomers. The highly specific diastereomeric coupling is explained by the surface alignment of educt in combination with the strong steric overcrowding in a possible surface-confined (M,P)-product.

Electrical Impedance Tomography Identifies Evolution of Regional Perfusion in a Porcine Model of Acute Respiratory Distress Syndrome.

BACKGROUND: Bedside electrical impedance tomography could be useful to visualize evolving pulmonary perfusion distributions when acute respiratory distress syndrome worsens or in response to ventilatory and positional therapies. In experimental acute respiratory distress syndrome, this study evaluated the agreement of electrical impedance tomography and dynamic contrast-enhanced computed tomography perfusion distributions at two injury time points and in response to increased positive end-expiratory pressure (PEEP) and prone position. METHODS: Eleven mechanically ventilated (VT 8 ml · kg-1) Yorkshire pigs (five male, six female) received bronchial hydrochloric acid (3.5 ml · kg-1) to invoke lung injury. Electrical impedance tomography and computed tomography perfusion images were obtained at 2 h (early injury) and 24 h (late injury) after injury in supine position with PEEP 5 and 10 cm H2O. In eight animals, electrical impedance tomography and computed tomography perfusion imaging were also conducted in the prone position. Electrical impedance tomography perfusion (QEIT) and computed tomography perfusion (QCT) values (as percentages of image total) were compared in eight vertical regions across injury stages, levels of PEEP, and body positions using mixed-effects linear regression. The primary outcome was agreement between QEIT and QCT, defined using limits of agreement and Pearson correlation coefficient. RESULTS: Pao2/Fio2 decreased over the course of the experiment (healthy to early injury, -253 [95% CI, -317 to -189]; early to late injury, -88 [95% CI, -151 to -24]). The limits of agreement between QEIT and QCT were -4.66% and 4.73% for the middle 50% quantile of average regional perfusion, and the correlation coefficient was 0.88 (95% CI, 0.86 to 0.90]; P < 0.001). Electrical impedance tomography and computed tomography showed similar perfusion redistributions over injury stages and in response to increased PEEP. QEIT redistributions after positional therapy underestimated QCT in ventral regions and overestimated QCT in dorsal regions. CONCLUSIONS: Electrical impedance tomography closely approximated computed tomography perfusion measures in experimental acute respiratory distress syndrome, in the supine position, over injury progression and with increased PEEP. Further validation is needed to determine the accuracy of electrical impedance tomography in measuring perfusion redistributions after positional changes.

Unsupervised segmentation and quantification of COVID-19 lesions on computed Tomography scans using CycleGAN.

BACKGROUND: Lesion segmentation is a critical step in medical image analysis, and methods to identify pathology without time-intensive manual labeling of data are of utmost importance during a pandemic and in resource-constrained healthcare settings. Here, we describe a method for fully automated segmentation and quantification of pathological COVID-19 lung tissue on chest Computed Tomography (CT) scans without the need for manually segmented training data. METHODS: We trained a cycle-consistent generative adversarial network (CycleGAN) to convert images of COVID-19 scans into their generated healthy equivalents. Subtraction of the generated healthy images from their corresponding original CT scans yielded maps of pathological tissue, without background lung parenchyma, fissures, airways, or vessels. We then used these maps to construct three-dimensional lesion segmentations. Using a validation dataset, Dice scores were computed for our lesion segmentations and other published segmentation networks using ground truth segmentations reviewed by radiologists. RESULTS: The COVID-to-Healthy generator eliminated high Hounsfield unit (HU) voxels within pulmonary lesions and replaced them with lower HU voxels. The generator did not distort normal anatomy such as vessels, airways, or fissures. The generated healthy images had higher gas content (2.45 ± 0.93 vs 3.01 ± 0.84 L, P < 0.001) and lower tissue density (1.27 ± 0.40 vs 0.73 ± 0.29 Kg, P < 0.001) than their corresponding original COVID-19 images, and they were not significantly different from those of the healthy images (P < 0.001). Using the validation dataset, lesion segmentations scored an average Dice score of 55.9, comparable to other weakly supervised networks that do require manual segmentations. CONCLUSION: Our CycleGAN model successfully segmented pulmonary lesions in mild and severe COVID-19 cases. Our model's performance was comparable to other published models; however, our model is unique in its ability to segment lesions without the need for manual segmentations.

Activation of the Calcium Receptor by Calcimimetic Agents Is Preserved Despite Modest Attenuating Effects of Hyperphosphatemia.

BACKGROUND: Phosphorus levels in the range seen clinically among patients undergoing dialysis have been reported to attenuate calcium receptor activation and modify parathyroid hormone (PTH) release from isolated parathyroid glands in vitro. Some clinicians and providers of dialysis thus have suggested that calcimimetic agents are ineffective and should not be used to manage secondary hyperparathyroidism among those undergoing dialysis when serum phosphorus concentrations exceed certain threshold levels. METHODS: To determine whether hyperphosphatemia diminishes the therapeutic response to calcimimetic agents, we used data from large clinical trials to analyze the effects of etelcalcetide and cinacalcet to lower plasma PTH levels in individuals on hemodialysis who had secondary hyperparathyroidism and varying degrees of hyperphosphatemia. RESULTS: Plasma PTH levels declined progressively during 26 weeks of treatment with either etelcalcetide or cinacalcet without regard to the degree of hyperphosphatemia at baseline. However, with each calcimimetic agent, the decreases in PTH from baseline were less at each interval of follow-up during the trials among participants with serum phosphorus levels above one of three prespecified threshold values compared with those with serum phosphorus levels below these thresholds. CONCLUSIONS: These in vivo findings are the first in humans to support the idea that hyperphosphatemia attenuates calcium receptor activation by calcium ions and by calcimimetic agents. The effect of hyperphosphatemia on the responsiveness to calcimimetic agents appears relatively modest, however, and unlikely to be significant therapeutically. The efficacy of treatment with calcimimetic agents for lowering plasma PTH levels among those with secondary hyperparathyroidism remains robust despite substantial elevations in serum phosphorus.

Imatinib alleviates lung injury and prolongs survival in ventilated rats.

Imatinib, a tyrosine kinase inhibitor, attenuates pulmonary edema and inflammation in lung injury. However, the physiological effects of this drug and their impact on outcomes are poorly characterized. Using serial computed tomography (CT), we tested the hypothesis that imatinib reduces injury severity and improves survival in ventilated rats. Hydrochloric acid (HCl) was instilled in the trachea (pH 1.5, 2.5 mL/kg) of anesthetized, intubated supine rats. Animals were randomized (n = 17 each group) to receive intraperitoneal imatinib or vehicle immediately prior to HCl. All rats then received mechanical ventilation. CT was performed hourly for 4 h. Images were quantitatively analyzed to assess the progression of radiological abnormalities. Injury severity was confirmed via hourly blood gases, serum biomarkers, bronchoalveolar lavage (BAL), and histopathology. Serial blood drug levels were measured in a subset of rats. Imatinib reduced mortality while delaying functional and radiological injury progression: out of 17 rats per condition, 2 control vs. 8 imatinib-treated rats survived until the end of the experiment (P = 0.02). Imatinib attenuated edema after lung injury (P < 0.05), and survival time in both groups was negatively correlated with increased lung mass (R2 = 0.70) as well as other physiological and CT parameters. Capillary leak (BAL protein concentration) was significantly lower in the treated group (P = 0.04). Peak drug concentration was reached after 70 min, and the drug half-life was 150 min. Imatinib decreased both mortality and lung injury severity in mechanically ventilated rats. Pharmacological inhibition of edema could be used during mechanical ventilation to improve the severity and outcome of lung injury.

Disruption of c-di-GMP Signaling Networks Unlocks Cryptic Expression of Secondary Metabolites during Biofilm Growth in Burkholderia pseudomallei.

The regulation and production of secondary metabolites during biofilm growth of Burkholderia spp. is not well understood. To learn more about the crucial role and regulatory control of cryptic molecules produced during biofilm growth, we disrupted c-di-GMP signaling in Burkholderia pseudomallei, a soilborne bacterial saprophyte and the etiologic agent of melioidosis. Our approach to these studies combined transcriptional profiling with genetic deletions that targeted key c-di-GMP regulatory components to characterize responses to changes in temperature. Mutational analyses and conditional expression studies of c-di-GMP genes demonstrates their contribution to phenotypes such as biofilm formation, colony morphology, motility, and expression of secondary metabolite biosynthesis when grown as a biofilm at different temperatures. RNA-seq analysis was performed at various temperatures in a ΔII2523 mutant background that is responsive to temperature alterations resulting in hypobiofilm- and hyperbiofilm-forming phenotypes. Differential regulation of genes was observed for polysaccharide biosynthesis, secretion systems, and nonribosomal peptide and polyketide synthase (NRPS/PKS) clusters in response to temperature changes. Deletion mutations of biosynthetic gene clusters (BGCs) 2, 11, 14 (syrbactin), and 15 (malleipeptin) in parental and ΔII2523 backgrounds also reveal the contribution of these BGCs to biofilm formation and colony morphology in addition to inhibition of Bacillus subtilis and Rhizoctonia solani. Our findings suggest that II2523 impacts the regulation of genes that contribute to biofilm formation and competition. Characterization of cryptic BGCs under different environmental conditions will allow for a better understanding of the role of secondary metabolites in the context of biofilm formation and microbe-microbe interactions. IMPORTANCE Burkholderia pseudomallei is a saprophytic bacterium residing in the environment that switches to a pathogenic lifestyle during infection of a wide range of hosts. The environmental cues that serve as the stimulus to trigger this change are largely unknown. However, it is well established that the cellular level of c-di-GMP, a secondary signal messenger, controls the switch from growth as planktonic cells to growth as a biofilm. Disrupting the signaling mediated by c-di-GMP allows for a better understanding of the regulation and the contribution of the surface associated and secreted molecules that contribute to the various lifestyles of this organism. The genome of B. pseudomallei also encodes cryptic biosynthetic gene clusters predicted to encode small molecules that potentially contribute to growth as a biofilm, adaptation, and interactions with other organisms. A better understanding of the regulation of these molecules is crucial to understanding how this versatile pathogen alters its lifestyle.

"I have the strength to get through this using my past experiences with HIV": findings from a mixed-method survey of health outcomes, service accessibility, and psychosocial wellbeing among people living with HIV during the Covid-19 pandemic.

We examined the impact of Covid-19 restrictions on the wellbeing and access to care among people living with HIV (PLWH) in the UK. A cross-sectional anonymous online survey was circulated to PLWH attending care at three HIV services in Sussex. The questionnaire covered key themes: socio-demographic characteristics; changes in physical and mental health; accessibility of essential health services and information; and socio-economic concerns. Free-text qualitative responses were examined through framework analysis. Quantitative data from 653 respondents were available, with a subset of 385 free-text qualitative responses. In terms of mental health, 501 (77.6%) respondents reported feeling more anxious; 464 (71.8%) reported feeling more depressed than usual; and 128 (19.8%) reported having suicidal thoughts since the start of the pandemic. Respondents worried about running out of HIV medicine (n = 264, 40.7%); accessing HIV services (n = 246, 38.0%) as well as other health services (n = 408, 63.0%). Widespread resilience was also noted: 537 (83.3%) of respondents felt that living with HIV had equipped them with the strength to adapt to the Covid-19 pandemic. Findings highlight important gaps between the multifaceted needs of PLWH. Multisectoral collaborations and investments are needed to adequately support PLWH and to build resilience to future shocks within HIV services.

Facilitators and barriers to point-of-care testing for sexually transmitted infections in low- and middle-income countries: a scoping review.

BACKGROUND: Sexually transmitted infections (STIs) in low- and middle-income countries (LMICs) are predominantly managed by syndromic management. However, most STIs are asymptomatic. These untreated STIs cause individual morbidity, and lead to high STI prevalences. There is increasing interest in the use of point-of-care tests (POCTs) for STIs in LMICs, which could facilitate same day testing and treatment. To best utilise these tests, we must understand the facilitators and barriers to their implementation. The aim of this review is to explore how point-of-care testing for STIs has been implemented into healthcare systems in LMIC and the facilitators and barriers to doing so. METHODS: A scoping review was conducted by searching MEDLINE, Embase, Emcare, CINAHL, Scopus, LILACS, the Cochrane Library, and ProQuest Dissertations and Theses for studies published between 1st January 1998 and 5th June 2020. Abstracts and full articles were screened independently by two reviewers. Studies were considered for inclusion if they assessed the acceptability, feasibility, facilitators, or barriers to implementation of point-of-care testing for chlamydia, gonorrhoea, trichomoniasis or syphilis in LMICs. Thematic analysis was used to analyse and present the facilitators and barriers to point-of-care STI testing. RESULTS: The literature search revealed 82 articles suitable for inclusion; 44 (53.7%) from sub-Saharan Africa; 21 (25.6%) from Latin American and the Caribbean; 10 (12.2%) from East Asia and the Pacific; 6 (7.3%) from South Asia; and one (1.2%) multi-regional study. Thematic analysis revealed seven overarching themes related to the implementation of POCTs in LMICs, namely (i) Ideal test characteristics, (ii) Client factors, (iii) Healthcare provision factors, (iv) Policy, infrastructure and health system factors, (v) Training, audit, and feedback, (vi) Reaching new testing environments, and (vii) Dual testing. CONCLUSION: Implementation of POCTs in LMICs is complex, with many of the barriers due to wider health system weakness. In addition to pressing for broader structural change to facilitate basic healthcare delivery, these themes may also be used as a basis on which to develop future interventions. The literature was heavily skewed towards syphilis testing, and so more research needs to be conducted assessing chlamydia, gonorrhoea, and trichomoniasis testing, as well as home or self-testing.

"It was difficult to offer same day results": evaluation of community-based point-of-care testing for sexually transmitted infections among youth using the GeneXpert platform in Zimbabwe.

BACKGROUND: Point-of-care testing for sexually transmitted infections (STIs) may improve diagnosis and treatment of STIs in low- and middle-income counties. We explored the facilitators and barriers to point-of-care testing for Chlamydia trachomatis (CT) and Neisseria gonorrhoea (NG) for youth in community-based settings in Zimbabwe. METHODS: This study was nested within a cluster randomised trial of community-based delivery of integrated HIV and sexual and reproductive health services for youth aged 16 to 24 years. On-site CT/NG testing on urine samples using the Xpert® CT/NG test was piloted in four intervention clusters, with testing performed by service providers. On-site testing was defined as sample processing on the same day and site as sample collection. Outcomes included proportion of tests processed on-site, time between sample collection and collection of results, and proportion of clients receiving treatment. In-depth interviews were conducted with nine service providers and three staff members providing study co-ordination or laboratory support to explore facilitators and barriers to providing on-site CT/NG testing. RESULTS: Of 847 Xpert tests, 296 (35.0%) were performed on-site. Of these, 61 (20.6%) were positive for CT/NG; one (1.6%) received same day aetiological treatment; 33 (54.1%) presented later for treatment; and 5 (8.2%) were treated as a part of syndromic management. There was no difference in the proportion of clients who were treated whether their sample was processed on or off-site (64% (39/61) vs 60% (66/110); p = 0.61). The median (IQR) number of days between sample collection and collection of positive results was 14 (7-35) and 14 (7-52.5) for samples processed on and off-site, respectively, The interviews revealed four themes related to the provision of on-site testing associated with the i) diagnostic device ii) environment, iii) provider, and iv) clients. Some of the specific barriers identified included insufficient testing capacity, inadequate space, as well as reluctance of clients to wait for their results. CONCLUSIONS: In addition to research to optimise the implementation of point-of-care tests for STIs in resource-limited settings, the development of new platforms to reduce analytic time will be necessary to scale up STI testing and reduce the attrition between testing and treatment. TRIAL REGISTRATION: Registered in clinical trials.gov ( NCT03719521 ).

2-Aminoimidazoles Inhibit Mycobacterium abscessus Biofilms in a Zinc-Dependent Manner.

Biofilm growth is thought to be a significant obstacle to the successful treatment of Mycobacterium abscessus infections. A search for agents capable of inhibiting M. abscessus biofilms led to our interest in 2-aminoimidazoles and related scaffolds, which have proven to display antibiofilm properties against a number of Gram-negative and Gram-positive bacteria, including Mycobacterium tuberculosis and Mycobacterium smegmatis. The screening of a library of 30 compounds led to the identification of a compound, AB-2-29, which inhibits the formation of M. abscessus biofilms with an IC50 (the concentration required to inhibit 50% of biofilm formation) in the range of 12.5 to 25 µM. Interestingly, AB-2-29 appears to chelate zinc, and its antibiofilm activity is potentiated by the addition of zinc to the culture medium. Preliminary mechanistic studies indicate that AB-2-29 acts through a distinct mechanism from those reported to date for 2-aminoimidazole compounds.

Utilizing A Percutaneous Versus Open Achilles Tendon Repair Technique for Treating Acute Achilles Tendon Ruptures in Physically Active Adults: A Critically Appraised Topic.

CLINICAL SCENARIO: Acute Achilles tendon ruptures can be devastating injuries with the potential to significantly alter an individual's ability to perform functional activities. Given the rise in the incidence of acute Achilles tendon ruptures, it is important to determine whether percutaneous versus open Achilles tendon repair facilitates superior outcomes. CLINICAL QUESTION: In physically active adults with an acute Achilles tendon rupture, does performing percutaneous Achilles tendon repair result in improved outcomes compared with open Achilles tendon repair? SUMMARY OF KEY FINDINGS: Percutaneous Achilles tendon repair has similar efficacy as open Achilles tendon repair in facilitating return to activity/sport, and demonstrates improvement in short-term functional outcomes with potentially lower wound complication rates. CLINICAL BOTTOM LINE: Evidence supports the utilization of percutaneous Achilles tendon repair in physically active adult patients with acute Achilles tendon ruptures. It is important to critically review the benefits, risks, and alternatives of each treatment option based on patient characteristics. In addition, postoperative expectations should be discussed with the patient to set appropriate goals for recovery and improve overall satisfaction. STRENGTH OF RECOMMENDATION: A grade B recommendation can be made based on "fair" to "good" evidence from 2 level 2b studies and 1 Level 1b study to support the utilization of percutaneous Achilles tendon repair techniques.

Diminishing Efficacy of Prone Positioning With Late Application in Evolving Lung Injury.

OBJECTIVES: It is not known how lung injury progression during mechanical ventilation modifies pulmonary responses to prone positioning. We compared the effects of prone positioning on regional lung aeration in late versus early stages of lung injury. DESIGN: Prospective, longitudinal imaging study. SETTING: Research imaging facility at The University of Pennsylvania (Philadelphia, PA) and Medical and Surgical ICUs at Massachusetts General Hospital (Boston, MA). SUBJECTS: Anesthetized swine and patients with acute respiratory distress syndrome (acute respiratory distress syndrome). INTERVENTIONS: Lung injury was induced by bronchial hydrochloric acid (3.5 mL/kg) in 10 ventilated Yorkshire pigs and worsened by supine nonprotective ventilation for 24 hours. Whole-lung CT was performed 2 hours after hydrochloric acid (Day 1) in both prone and supine positions and repeated at 24 hours (Day 2). Prone and supine images were registered (superimposed) in pairs to measure the effects of positioning on the aeration of each tissue unit. Two patients with early acute respiratory distress syndrome were compared with two patients with late acute respiratory distress syndrome, using electrical impedance tomography to measure the effects of body position on regional lung mechanics. MEASUREMENTS AND MAIN RESULTS: Gas exchange and respiratory mechanics worsened over 24 hours, indicating lung injury progression. On Day 1, prone positioning reinflated 18.9% ± 5.2% of lung mass in the posterior lung regions. On Day 2, position-associated dorsal reinflation was reduced to 7.3% ± 1.5% (p < 0.05 vs Day 1). Prone positioning decreased aeration in the anterior lungs on both days. Although prone positioning improved posterior lung compliance in the early acute respiratory distress syndrome patients, it had no effect in late acute respiratory distress syndrome subjects. CONCLUSIONS: The effects of prone positioning on lung aeration may depend on the stage of lung injury and duration of prior ventilation; this may limit the clinical efficacy of this treatment if applied late.

Stereospecific on-Surface Cyclodehydrogenation of Bishelicenes: Preservation of Handedness from Helical to Planar Chirality.

Flattening helices while keeping the handedness: On-surface cyclodehydrogenation of bishelicene enantiomers leads stereospecifically to (M,M) and (P,P) chiral planar polyaromatic hydrocarbons. This is followed by their homochiral aggregation into a 2D conglomerate. Thermally induced cyclodehydrogenation proceeds stereospecifically to chiral, planar coronocoronene. Such a reaction is a special example of topochemistry in which enantiospecific conversion is supported by the alignment of the reactant by the surface.

Identifying youth at high risk for sexually transmitted infections in community-based settings using a risk prediction tool: a validation study.

BACKGROUND : Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are the most common bacterial sexually transmitted infections (STIs) worldwide. In the absence of affordable point-of-care STI tests, WHO recommends STI testing based on risk factors. This study aimed to develop a prediction tool with a sensitivity of > 90% and efficiency (defined as the percentage of individuals that are eligible for diagnostic testing) of < 60%. METHODS: This study offered CT/NG testing as part of a cluster-randomised trial of community-based delivery of sexual and reproductive health services to youth aged 16-24 years in Zimbabwe. All individuals accepting STI testing completed an STI risk factor questionnaire. The outcome was positivity for either CT or NG. Backwards-stepwise logistic regression was performed with p ≥ 0.05 as criteria for exclusion. Coefficients of variables included in the final multivariable model were multiplied by 10 to generate weights for a STI risk prediction tool. A maximum likelihood Receiver Operating Characteristics (ROC) model was fitted, with the continuous variable score divided into 15 categories of equal size. Sensitivity, efficiency and number needed to screen were calculated for different cut-points. RESULTS: From 3 December 2019 to 5 February 2020, 1007 individuals opted for STI testing, of whom 1003 (99.6%) completed the questionnaire. CT/NG prevalence was 17.5% (95% CI 15.1, 19.8) (n = 175). CT/NG positivity was independently associated with being female, number of lifetime sexual partners, relationship status, HIV status, self-assessed STI risk and past or current pregnancy. The STI risk prediction score including those variables ranged from 2 to 46 with an area under the ROC curve of 0.72 (95% CI 0.68, 0.76). Two cut-points were chosen: (i) 23 for optimised sensitivity (75.9%) and specificity (59.3%) and (ii) 19 to maximise sensitivity (82.4%) while keeping efficiency at < 60% (59.4%). CONCLUSIONS: The high prevalence of STIs among youth, even in those with no or one reported risk factor, may preclude the use of risk prediction tools for selective STI testing. At a cut-point of 19 one in six young people with STIs would be missed.

'I care a lot' a commentary on the depiction of elder abuse in the film.

In I Care a Lot, we follow Marla Grayson, a self-proclaimed "Professional Carer" who makes a living by financially abusing older adults. Elder abuse, financial or otherwise, is seldom explored in cinema and must be handled with care. Cinema can help raise awareness on this social problem and play an important role in the de-stigmatization of older adults. Unfortunately, in our opinion, I Care a Lot fails to do so.

Provincial Door-to-Needle Improvement Initiative Results in Improved Patient Outcomes Across an Entire Population.

BACKGROUND AND PURPOSE: Improving door-to-needle times (DNTs) for thrombolysis of acute ischemic stroke patients improves outcomes, but participation in DNT improvement initiatives has been mostly limited to larger, academic medical centers with an existing interest in stroke quality improvement. It is not known whether quality improvement initiatives can improve DNT at a population level, including smaller community hospitals. This study aims to determine the effect of a provincial improvement collaborative intervention on improvement of DNT and patient outcomes. METHODS: A pre post cohort study was conducted over 10 years in the Canadian province of Alberta with 17 designated stroke centers. All ischemic stroke patients who received thrombolysis in the Canadian province of Alberta were included in the study. The quality improvement intervention was an improvement collaborative that involved creation of interdisciplinary teams from each stroke center, participation in 3 workshops and closing celebration, site visits, webinars, and data audit and feedback. RESULTS: Two thousand four hundred eighty-eight ischemic stroke patients received thrombolysis in the pre- and postintervention periods (630 in the post period). The mean age was 71 years (SD, 14.6 years), and 46% were women. DNTs were reduced from a median of 70.0 minutes (interquartile range, 51-93) to 39.0 minutes (interquartile range, 27-58) for patients treated per guideline (P<0.0001). The percentage of patients discharged home from acute care increased from 45.6% to 59.5% (P<0.0001); the median 90-day home time increased from 43.3 days (interquartile range, 27.3-55.8) to 53.6 days (interquartile range, 36.8-64.6) (P=0.0015); and the in-hospital mortality decreased from 14.5% to 10.5% (P=0.0990). CONCLUSIONS: The improvement collaborative was likely the key contributing factor in reducing DNTs and improving outcomes for ischemic stroke patients across Alberta.