Serosurveillance for Measles and Rubella.

Measles and rubella remain global health threats, despite the availability of safe and effective vaccines. Estimates of population immunity are crucial for achieving elimination goals and assessing the impact of vaccination programs, yet conducting well-designed serosurveys can be challenging, especially in resource-limited settings. In this review, we provide a comprehensive assessment of 130 measles and rubella studies published from January 2014 to January 2024. Methodologies and design aspects of serosurveys varied greatly, including sample size, assay type, and population demographics. Most studies utilized enzyme immunoassays for IgG detection. Sample sizes showed diverse sampling methods but favored convenience sampling despite its limitations. Studies spanned 59 countries, predominantly including adults, and revealed disparities in seroprevalence across demographics, regions, and notably among migrants and women. Age-related declines in antibodies were observed, particularly among infants, and correlations between vaccination status and seropositivity varied. We conclude with an outlook on measles and rubella serosurveillance, emphasizing the need for proper survey design and the advantages of standardized, multiplex serology assays.

Privacy-preserving model evaluation for logistic and linear regression using homomorphically encrypted genotype data.

OBJECTIVE: Linear and logistic regression are widely used statistical techniques in population genetics for analyzing genetic data and uncovering patterns and associations in large genetic datasets, such as identifying genetic variations linked to specific diseases or traits. However, obtaining statistically significant results from these studies requires large amounts of sensitive genotype and phenotype information from thousands of patients, which raises privacy concerns. Although cryptographic techniques such as homomorphic encryption offers a potential solution to the privacy concerns as it allows computations on encrypted data, previous methods leveraging homomorphic encryption have not addressed the confidentiality of shared models, which can leak information about the training data. METHODS: In this work, we present a secure model evaluation method for linear and logistic regression using homomorphic encryption for six prediction tasks, where input genotypes, output phenotypes, and model parameters are all encrypted. RESULTS: Our method ensures no private information leakage during inference and achieves high accuracy (≥93% for all outcomes) with each inference taking less than ten seconds for ∼200 genomes. CONCLUSION: Our study demonstrates that it is possible to perform linear and logistic regression model evaluation while protecting patient confidentiality with theoretical security guarantees. Our implementation and test data are available at https://github.com/G2Lab/privateML/.

Chest ultrasonography versus supine chest radiography for diagnosis of pneumothorax in trauma patients in the emergency department.

BACKGROUND: Chest X-ray (CXR) is a longstanding method for the diagnosis of pneumothorax but chest ultrasonography (CUS) may be a safer, more rapid, and more accurate modality in trauma patients at the bedside that does not expose the patient to ionizing radiation. This may lead to improved and expedited management of traumatic pneumothorax and improved patient safety and clinical outcomes. OBJECTIVES: To compare the diagnostic accuracy of chest ultrasonography (CUS) by frontline non-radiologist physicians versus chest X-ray (CXR) for diagnosis of pneumothorax in trauma patients in the emergency department (ED). To investigate the effects of potential sources of heterogeneity such as type of CUS operator (frontline non-radiologist physicians), type of trauma (blunt vs penetrating), and type of US probe on test accuracy. SEARCH METHODS: We conducted a comprehensive search of the following electronic databases from database inception to 10 April 2020: Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL) Plus, Database of Abstracts of Reviews of Effects, Web of Science Core Collection and Clinicaltrials.gov. We handsearched reference lists of included articles and reviews retrieved via electronic searching; and we carried out forward citation searching of relevant articles in Google Scholar and looked at the "Related articles" on PubMed. SELECTION CRITERIA: We included prospective, paired comparative accuracy studies comparing CUS performed by frontline non-radiologist physicians to supine CXR in trauma patients in the emergency department (ED) suspected of having pneumothorax, and with computed tomography (CT) of the chest or tube thoracostomy as the reference standard. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from each included study using a data extraction form. We included studies using patients as the unit of analysis in the main analysis and we included those using lung fields in the secondary analysis. We performed meta-analyses by using a bivariate model to estimate and compare summary sensitivities and specificities. MAIN RESULTS: We included 13 studies of which nine (410 traumatic pneumothorax patients out of 1271 patients) used patients as the unit of analysis; we thus included them in the primary analysis. The remaining four studies used lung field as the unit of analysis and we included them in the secondary analysis. We judged all studies to be at high or unclear risk of bias in one or more domains, with most studies (11/13, 85%) being judged at high or unclear risk of bias in the patient selection domain. There was substantial heterogeneity in the sensitivity of supine CXR amongst the included studies. In the primary analysis, the summary sensitivity and specificity of CUS were 0.91 (95% confidence interval (CI) 0.85 to 0.94) and 0.99 (95% CI 0.97 to 1.00); and the summary sensitivity and specificity of supine CXR were 0.47 (95% CI 0.31 to 0.63) and 1.00 (95% CI 0.97 to 1.00). There was a significant difference in the sensitivity of CUS compared to CXR with an absolute difference in sensitivity of 0.44 (95% CI 0.27 to 0.61; P < 0.001). In contrast, CUS and CXR had similar specificities: comparing CUS to CXR, the absolute difference in specificity was -0.007 (95% CI -0.018 to 0.005, P = 0.35). The findings imply that in a hypothetical cohort of 100 patients if 30 patients have traumatic pneumothorax (i.e. prevalence of 30%), CUS would miss 3 (95% CI 2 to 4) cases (false negatives) and overdiagnose 1 (95% CI 0 to 2) of those without pneumothorax (false positives); while CXR would miss 16 (95% CI 11 to 21) cases with 0 (95% CI 0 to 2) overdiagnosis of those who do not have pneumothorax. AUTHORS' CONCLUSIONS: The diagnostic accuracy of CUS performed by frontline non-radiologist physicians for the diagnosis of pneumothorax in ED trauma patients is superior to supine CXR, independent of the type of trauma, type of CUS operator, or type of CUS probe used. These findings suggest that CUS for the diagnosis of traumatic pneumothorax should be incorporated into trauma protocols and algorithms in future medical training programmes; and that CUS may beneficially change routine management of trauma.

Photodocumentation as an emergency department documentation tool in soft tissue infection: a randomized trial.

OBJECTIVES: Current documentation methods for patients with skin and soft tissue infections receiving outpatient parenteral anti-infective therapy (OPAT) include written descriptions and drawings of the infection that may inadequately communicate clinical status. We undertook a study to determine whether photodocumentation (PD) improves the duration of outpatient treatment of skin and soft tissue infections. METHODS: A single-blinded, prospective, randomized trial was conducted in the emergency departments of a community hospital and an academic tertiary centre. Participants included consecutive patients age ≥ 14 years presenting with noninvasive skin and soft tissue infections requiring OPAT. Patients in the intervention arm were treated with standard of care plus PD at each emergency physician assessment. Control subjects received care provided at the discretion of the treating physician and non-photographic documentation. The primary outcome was duration of therapy measured in half-days. The required sample size to detect a difference of one half-day was 253 patients per group (α  =  0.05). Secondary outcomes included (1) completion and therapeutic failure rates, (2) patient satisfaction, and (3) physician and nurse satisfaction. RESULTS: Enrolment was slower and follow-up rates lower than anticipated, and the trial was terminated when funds were exhausted. A total of 468 subjects with similar age and gender characteristics were enrolled, with 244 receiving the intervention and 224 in the control arm. The mean OPAT duration was similar in the two groups (3.6 days v. 3.5 days, p  =  0.73). No differences in the rate for completion and therapeutic failure were observed (71% v. 68% and < 1% for both, respectively). Survey response rates varied significantly: patients, 65%; nurses, 17%; and physicians, 87%. Physicians endorsed more comfort with their assessment and OPAT judgment with PD (65% and 64%, respectively). Physicians cited too much time lost with technological challenges, which would affect implementation in a busy ED. CONCLUSIONS: PD as an intervention is acceptable to patients and has reasonable endorsement by the majority of physicians. This trial had significant limitations that threatened the integrity of the study, so the results are inconclusive.

Intranasal ketamine for analgesia in the emergency department: a prospective observational series.

OBJECTIVES: The objective was to examine the feasibility, effectiveness, and adverse effect profile of intranasal ketamine for analgesia in emergency department (ED) patients. METHODS: This was a prospective observational study examining a convenience sample of patients aged older than 6 years experiencing moderate or severe pain, defined as a visual analog scale (VAS) score of 50 mm or greater. Patients received 0.5 to 0.75 mg/kg intranasal ketamine. Pain scores were recorded on a standard 100-mm VAS by trained investigators at baseline, then every 5 minutes for 30 minutes, and then every 10 minutes for an additional 30 minutes. The primary outcome was the number and proportion of patients experiencing clinically significant reductions in VAS pain scores, defined as VAS reductions of 13 mm or more, within 30 minutes. Secondary outcomes included the median reduction in VAS, the median time required to achieve a 13 mm reduction in VAS, vital sign changes, and adverse events. Continuous data are reported with medians and interquartile ranges (IQRs). The Wilcoxon signed-ranks test was used to assess changes in VAS scores. Adverse effects are reported with proportions and 95% confidence intervals (CIs). RESULTS: Forty patients were enrolled with a median age of 47 years (IQR = 36 to 57 years; range = 11 to 79 years) for primarily orthopedic injuries. A reduction in VAS of 13 mm or more within 30 minutes was achieved in 35 patients (88%). The median change in VAS at 30 minutes was 34 mm (44%). Median time required to achieve a 13 mm VAS reduction was 9.5 minutes (IQR = 5 to 13 minutes; range = 5 to 25 minutes). No serious adverse effects occurred. Minor adverse effects included dizziness (21 patients, 53%; 95% CI = 38% to 67%), feeling of unreality (14 patients, 35%; 95% CI = 22% to 50%), nausea (four patients, 10%; 95% CI = 4% to 23%), mood change (three patients, 8%; 95% CI = 3% to 20%), and changes in hearing (one patient, 3%; 95% CI = 0% to 13%). All adverse effects were transient and none required intervention. There were no changes in vital signs requiring clinical intervention. CONCLUSIONS: Intranasal ketamine reduced VAS pain scores to a clinically significant degree in 88% of ED patients in this series. Adverse effects were minor and transient. Intranasal ketamine may have a role in the provision of effective, expeditious analgesia to ED patients.

Notch signaling respecifies the hemangioblast to a cardiac fate.

To efficiently generate cardiomyocytes from embryonic stem (ES) cells in culture it is essential to identify key regulators of the cardiac lineage and to develop methods to control them. Using a tet-inducible mouse ES cell line to enforce expression of a constitutively activated form of the Notch 4 receptor, we show that signaling through the Notch pathway can efficiently respecify hemangioblasts to a cardiac fate, resulting in the generation of populations consisting of >60% cardiomyocytes. Microarray analyses reveal that this respecification is mediated in part through the coordinated regulation of the BMP and Wnt pathways by Notch signaling. Together, these findings have uncovered a potential role for the Notch pathway in cardiac development and provide an approach for generating large numbers of cardiac progenitors from ES cells.

Copper and quaternary ammonium cations exert synergistic bactericidal and antibiofilm activity against Pseudomonas aeruginosa.

Biofilms are slimy aggregates of microbes that are likely responsible for many chronic infections as well as for contamination of clinical and industrial environments. Pseudomonas aeruginosa is a prevalent hospital pathogen that is well known for its ability to form biofilms that are recalcitrant to many different antimicrobial treatments. We have devised a high-throughput method for testing combinations of antimicrobials for synergistic activity against biofilms, including those formed by P. aeruginosa. This approach was used to look for changes in biofilm susceptibility to various biocides when these agents were combined with metal ions. This process identified that Cu(2+) works synergistically with quaternary ammonium compounds (QACs; specifically benzalkonium chloride, cetalkonium chloride, cetylpyridinium chloride, myristalkonium chloride, and Polycide) to kill P. aeruginosa biofilms. In some cases, adding Cu(2+) to QACs resulted in a 128-fold decrease in the biofilm minimum bactericidal concentration compared to that for single-agent treatments. In combination, these agents retained broad-spectrum antimicrobial activity that also eradicated biofilms of Escherichia coli, Staphylococcus aureus, Salmonella enterica serovar Cholerasuis, and Pseudomonas fluorescens. To investigate the mechanism of action, isothermal titration calorimetry was used to show that Cu(2+) and QACs do not interact in aqueous solutions, suggesting that each agent exerts microbiological toxicity through independent biochemical routes. Additionally, Cu(2+) and QACs, both alone and in combination, reduced the activity of nitrate reductases, which are enzymes that are important for normal biofilm growth. Collectively, the results of this study indicate that Cu(2+) and QACs are effective combinations of antimicrobials that may be used to kill bacterial biofilms.

A complementary transposon tool kit for Drosophila melanogaster using P and piggyBac.

With the availability of complete genome sequence for Drosophila melanogaster, one of the next strategic goals for fly researchers is a complete gene knockout collection. The P-element transposon, the workhorse of D. melanogaster molecular genetics, has a pronounced nonrandom insertion spectrum. It has been estimated that 87% saturation of the approximately 13,500-gene complement of D. melanogaster might require generating and analyzing up to 150,000 insertions. We describe specific improvements to the lepidopteran transposon piggyBac and the P element that enabled us to tag and disrupt genes in D. melanogaster more efficiently. We generated over 29,000 inserts resulting in 53% gene saturation and a more diverse collection of phenotypically stronger insertional alleles. We found that piggyBac has distinct global and local gene-tagging behavior from that of P elements. Notably, piggyBac excisions from the germ line are nearly always precise, piggyBac does not share chromosomal hotspots associated with P and piggyBac is more effective at gene disruption because it lacks the P bias for insertion in 5' regulatory sequences.

Chlamydia pneumoniae e aterosclerose: identificaçäo do DNA bacteriano na parede arterial / Chlamydia pneumoniae and atherosclerosis: identification of bacterial DNA in the arterial wall

OBJECTIVE : The intracellular Gram-negative bacterium Chlamydia pneumoniae has been associated with atherosclerosis. The presence of Chlamydia pneumoniae has been investigated in fragments of the arterial. METHODS: Arterial fragments obtained from vascular surgical procedures in 58 patients were analyzed. From these patients, 39 were males and the mean age was 65ñ6 years. The polymerase chain reaction was used to identify the bacterial DNA with a pair of primers that codify the major outer membrane protein (MOMP) of Chlamydia pneumoniae. The amplified product was visualized by electrophoresis in the 2 porcento agarose gel stained with ethidium bromide, and it was considered positive when migrating in the band of molecular weight of the positive controls. RESULTS: Seven (12 per cent) out of the 58 patients showed positive results for Chlamydia pneumoniae. CONCLUSION: DNA from Chlamydia pneumoniae was identified in the arterial wall of a substantial number of patients with atherosclerosis. This association, which has already been described in other countries, corroborates the evidence favoring a role played by Chlamydia pneumoniae in therogenesis.