Serial Testing Research Articles

The activity of leaf extracts, fractions, and isolated compounds from Ptaeroxylon obliquum against nine phytopathogenic fungi and the nematode Meloidogyne incognita

Phytopathogenic fungi and nematodes cause great losses in economically important crops and food production especially in developing countries. To minimize the use of fungicides and nematicides, researchers have concentrated on the use of natural products for crop disease prevention or control. The aim of the study was to investigate the antifungal activity of Ptaeroxylon obliquum leaf extracts, fractions, and isolated compounds (obliquumol and a mixture of lupeol and β-amyrin) and nematocidal activity of fractions (hexane, chloroform and 30% water in methanol and the isolated compounds) on Meloidogyne incognita. Nine phytopathogenic fungi (Aspergillus niger, A. parasiticus, Colletotrichum gloeosporioides, Fusarium oxysporum, Penicillium digitatum, P. expansum, P. italicum, P. janthinellum, and Rhizoctonia solani) were used for testing and nematocidal activity was determined on motility of plant parasitic nematode Meloidogyne incognita race 2 juveniles. Serial microdilution test was utilized to determine the minimum inhibitory concentration (MIC) of each sample against the fungus. Motility tests was done on the second-stage juveniles (J2s) of M. incognita. The most susceptible phytopathogenic fungal species to the acetone crude leaf extracts were A. niger, C. gloeosporioides and P. digitatum with MIC of 80 μg/ml which is considered pharmacological significant. Rhizoctonia solani was the most susceptible fungus against obliquumol and, lupeol and β-amyrin mixture with MIC values of 8 μg/ml and 16 μg/ml respectively. Lupeol & β-amyrin mixture had good activity on juvenile motility at high concentrations used which was significantly high (p ≤ 0.05) after 24 h, further incubation resulted in temporary paralysis at lower concentrations. Fractions and obliquumol showed good activity after 48 h, stable paralysis was observed up to 72 h. The extracts and isolated compounds may be useful as fungicides if the in vitro results can be confirmed under field conditions at levels not toxic to beneficial soil organisms.

Structural and functional correlates of disability, motor and cognitive performances in multiple sclerosis: Focus on the globus pallidus

ObjectivesTo explore structural and functional alterations of external (GPe) and internal (GPi) globus pallidus in people with multiple sclerosis (pwMS) compared to healthy controls (HC) and analyze their relationship with measures of clinical disability, motor and cognitive impairment. MethodsSixty pwMS and 30 HC comparable for age and sex underwent 3.0T MRI, including conventional, diffusion tensor MRI and resting state (RS) functional MRI. Expanded Disability Status Scale (EDSS) scores were rated and timed 25-foot walk (T25FW) test, nine-hole peg test (9HPT), and paced auditory serial addition test (PASAT) were administered. Two operators segmented the GP into GPe and GPi. Volumes, T1/T2 ratio, diffusivity indices and seed-based RS functional connectivity (FC) of the GP and its components were assessed. ResultsPwMS had no atrophy or altered diffusivity measures of the GP. Compared to HC, pwMS had higher T1/T2 ratio in both GP regions, which correlated with EDSS score (r = 0.26–0.39, p = 0.01–0.05). RS FC analysis highlighted component-specific functional alterations in pwMS: the GPe had decreased RS FC with fronto-parietal cortices, whereas the GPi had decreased intra-GP RS FC and increased RS FC with the thalamus. Worse EDSS, 9HPT, T25FW and PASAT scores were associated with GP RS FC modifications (r=-0.51‒0.51, p < 0.001). ConclusionsStructural GP involvement in MS was homogeneous across its portions. Increased T1/T2 ratio values, possibly representing iron accumulation, were related to more severe disability. RS FC alterations of the GPe and GPi were consistent with their roles within the basal ganglia network and correlated with worse functional status, suggesting less efficient communication between structures.

Adapting the Multiple Sclerosis Functional Composite for Telehealth Administration Using Videoconference Delivery: Methodological Considerations and Interrater Reliability

ObjectiveTo describe the adaptations made and to examine interrater reliability and feasibility of administering a telehealth version of the Multiple Sclerosis Functional Composite (tele-MSFC). DesignThe Multiple Sclerosis Functional Composite (MSFC) is a commonly used, in-person clinical outcome assessment. It is composed of the timed 25-Foot Walk Test (T25FWT), Nine-Hole Peg Test (NHPT), and Paced Auditory Serial Addition Test (PASAT). The MSFC was adapted for videoconference administration as part of a larger clinical trial. One of the adaptations included administering a timed 12.5-Foot Walk Test (T12.5FWT) for participants who did not have adequate space in their homes for the T25FWT. Participants, examiners, and raters completed surveys online about their satisfaction and experience with tele-MSFC. SettingParticipants underwent the tele-MSFC in their homes using a laptop or smartphone while examiners scored the tele-MSFC in real-time at a remote location. ParticipantsCommunity-dwelling adults (n=61) with mild-to-moderate multiple sclerosis (MS) symptoms. InterventionsNot applicable. Main Outcome MeasureTele-MSFC. ResultsIntraclass correlation coefficients (ICC) assessed interrater reliability between the examiner and 2 independent raters who later scored a recording of the tele-MSFC. Interrater reliability was excellent (ICC>0.90) for all tests, including the T12.5FWT. Participants were highly satisfied with tele-MSFC. However, challenges included adequate space for T25FWT, technical difficulties, and safety and privacy considerations of individuals with moderate impairments who were requested to have their caregivers present during testing. ConclusionThe tele-MSFC is reliable and feasible to administer with adaptations for community-dwelling adults with mild to moderate MS symptoms. Further validation of T12.5FWT is needed.

Serial electrodiagnostic testing: Utility and indications in adult neurological disorders.

Although existing guidelines address electrodiagnostic (EDX) testing in identifying neuromuscular conditions, guidance regarding the uses and limitations of serial (or repeat) EDX testing is limited. By assessing neurophysiological change longitudinally across time, serial electrodiagnosis can clarify a diagnosis and potentially provide valuable prognostic information. This monograph presents four broad indications for serial electrodiagnosis in adult peripheral neurological disorders. First, where clinical change has raised suspicion for a new or ongoing lesion, EDX reassessment for spatial spread of abnormality, involvement of previously normal muscle or nerve, and/or evolving pathophysiology can clarify a diagnosis. Second, where diagnosis of a progressive neuromuscular condition is uncertain, electrophysiological data from a second time point can confirm or refute suspicion. Third, to establish prognosis after a static nerve injury, a repeat study can assess the presence and extent of reinnervation. Finally, faced with a limited initial study (as when complicated by patient or environmental factors), a repeat EDX study can supplement missing or limited data to provide needed clarity. Repeat EDX studies carry certain limitations, however, such as with prognostication in the setting of remote or chronic lesions, sensory predominant fascicular injury, or mild axonal injury. Nevertheless, serial electrodiagnosis remains a valuable and underused tool in the diagnostic and prognostic evaluation of neuromuscular conditions.

Outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 in a Rural Community Hospital during Omicron Predominance.

Healthcare-associated infections due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has increased since the discovery of the Omicron variant. We describe a SARS-CoV-2 outbreak in the medicine-surgery unit of a rural community hospital at the time of high community transmission of Omicron variant in our county. The outbreak occurred in the medicine-surgery unit of an 89-bed rural community hospital in northern Maine. The characteristics of the patients and healthcare workers (HCWs) affected by the outbreak are described. Patient and HCW data collected as part of the outbreak investigation were used in this report. The outbreak control measures implemented are also described. A total of 24 people tested positive for SARS-CoV-2 including 11 patients and 13 HCWs. A total of 12 of the 24 (50%) persons were symptomatic, and rhinorrhea was the most common symptom noted (8/12, 67%). None of the symptomatic persons had gastrointestinal symptoms or symptoms of a loss of sense of smell or taste. All HCWs were vaccinated and 8 of the 11 patients were vaccinated. Outbreak control measures in the affected unit included implementation of full PPE (N95 respirators, eye protection, gowns and gloves) during all patient care, serial testing of employees and patients in the affected unit, cohorting positive patients, closing visitation and thorough environmental cleaning including use of ultraviolet (UV) light disinfection. This outbreak exemplifies the high transmissibility of the Omicron variant of SARS-CoV-2. The outbreak occurred despite a well-established infection control program. We noted that serial testing, use of N95 respirators during all patient care and UV disinfection were some of the measures that could be successful in outbreak control.

Anxiety, depression, working from home and health-related behaviours during COVID-19: Structural equation modelling and serial mediation of associations with angina, heart attacks and stroke.

Based on the vulnerability-stress model and coping theory, this study of 1920 people in Scotland investigated how sex, age, occupational factors, anxiety, depression and maladaptive coping behaviours are associated with cardiovascular health. Structural equation modelling and serial Sobel mediation tests were conducted. Anxiety was associated with past arrhythmia, whereas depression was associated with past heart attacks, stroke and angina. Females reported more anxiety, past arrhythmia, confectionary and alcohol consumption, whereas males had more heart attacks. Confectionary consumption was associated with past arrhythmia, and alcohol consumption was associated with past heart attacks. Being older was associated with depression, past stroke, arrhythmia and alcohol consumption. Being younger was associated with anxiety and smoking. Depression and smoking mediated the relationship between type of working and cardiovascular health history, potentially because of socioeconomic factors. Clinicians can use these results to advise clients about cardiovascular risks associated with anxiety, depression, demographics and health-related coping behaviours.

Comparative Diagnostic Utility of SARS-CoV-2 Rapid Antigen and Molecular Testing in a Community Setting.

SARS-CoV-2 antigen-detection rapid diagnostic tests (Ag-RDTs) have become widely utilized but longitudinal characterization of their community-based performance remains incompletely understood. This prospective longitudinal study at a large public university in Seattle, WA utilized remote enrollment, online surveys, and self-collected nasal swab specimens to evaluate Ag-RDT performance against real-time reverse transcription polymerase chain reaction (rRT-PCR) in the context of SARS-CoV-2 Omicron. Ag-RDT sensitivity and specificity within 1 day of rRT-PCR were evaluated by symptom status throughout the illness episode and Orf1b cycle threshold (Ct). From February to December 2022, 5757 participants reported 17 572 Ag-RDT results and completed 12 674 rRT-PCR tests, of which 995 (7.9%) were rRT-PCR positive. Overall sensitivity and specificity were 53.0% (95% confidence interval [CI], 49.6%-56.4%) and 98.8% (95% CI, 98.5%-99.0%), respectively. Sensitivity was comparatively higher for Ag-RDTs used 1 day after rRT-PCR (69.0%), 4-7 days after symptom onset (70.1%), and Orf1b Ct ≤20 (82.7%). Serial Ag-RDT sensitivity increased with repeat testing ≥2 (68.5%) and ≥4 (75.8%) days after an initial Ag-RDT-negative result. Ag-RDT performance varied by clinical characteristics and temporal testing patterns. Our findings support recommendations for serial testing following an initial Ag-RDT-negative result, especially among recently symptomatic persons or those at high risk for SARS-CoV-2 infection.

Abstract 7493: Real-time monitoring of CTC number, biomarker expression, and kinetics as prognostic and predictive markers in patients with GI malignancies

Abstract Background: Most of the utility in the clinic regarding liquid biopsies has been around circulating tumor DNA (ctDNA). ctDNA analysis provides valuable insight into mutational burden and therapeutic targets, but the speed and cost of analysis are prohibitive especially when it comes to serial testing. Using a cohort of patients with advanced or metastatic gastrointestinal (GI) cancers, we herein show the feasibility of using circulating tumor cell (CTC) enumeration, biomarker analysis, and kinetics as complementary to or as an alternative to ctDNA testing. Methods: Using the RareCyte platform, nucleated cells from blood were collected, spread on slides, stained, and imaged with CyteFinder® for CTC identification (CK/EpCAM+, CD45-) and quantification of biomarkers (PD-L1/HER2 or Ki67/EGFR). CTC enumeration (CLIA-accredited CTC test) and biomarker status for each patient were tracked over time and compared with ctDNA mutational analysis and tumor burden. Results: CTCs were detected in 60/70 samples (86%) and in 36/38 unique patients (95%). On average, more CTCs were detected in baseline samples from colorectal cancer patients compared to other subtypes (Table 1). Moreover, multiple patients showed pronounced changes in CTC number that correlated with treatment response, as well as strong correlation between CTC and tissue biomarker expression e.g. HER2. Rapid decline and/or CTC clearance was seen as early as a few days into starting effective systemic therapy. The average turnaround time for CTC testing was 5-7 days. Table 1. CTC values in initial baseline blood draw sample Gastrointestinal cancer subtype # of patients Average # of CTCs per 7.5mL blood Median # of CTCs per 7.5mL blood Minimum # of CTCs per 7.5mL blood Maximum # of CTCs per 7.5mL blood Colorectal carcinoma 27 84 3 0 1378 Cholangiocarcinoma 3 8 3 1 23 Pancreatic cancer 3 2 2 0 3 Hepatocellular carcinoma 2 4 5 0 10 Gallbladder cancer 1 6 6 3 8 Appendix cancer 1 2 2 1 3 Anal cancer 1 0 0 0 0 Conclusions: Our study emphasizes that real-time monitoring of CTCs is complementary to traditional tumor burden monitoring via imaging and ctDNA analysis. CTCs offer multiple unique advantages vs ctDNA including early response assessment within days of initiating therapy, a substantial decrease in cost of serial testing, and the ability to assess clinically relevant cell surface protein biomarkers e.g. HER2 and PD-L1. Citation Format: Erin G. Bayer, Brock M. Bartels, Rachel N. Ponting, Areeb Lutfi, Maaz K. Afghan, Arturo B. Ramirez, Pashtoon M. Kasi. Real-time monitoring of CTC number, biomarker expression, and kinetics as prognostic and predictive markers in patients with GI malignancies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7493.

Abstract 2390: Longitudinal assessment of circulating tumor DNA in patients with advanced colorectal cancer: A proposed general statistical framework and visualization tool

Abstract Background: Understanding how ctDNA levels change over time can act as a surrogate marker for disease progression. Since ctDNA evolution is complicated—exhibiting variability within and between patients—we propose a rigorous and flexible statistical framework that comprehensively represents these types of time-varying biomarkers. We propose employing a hierarchal random effects cubic spline model due to its advantages over traditional longitudinal modeling approaches such as the former’s ability to incorporate patient characteristics and create patient-specific results. Visualization of individual patient trajectories may provide clinical utility in precision oncology settings. Methods: 167 patients with CRC were selected from GuardantINFORM, a real-world database linking genomic and claims data. All patients received chemotherapy and had at least three serial liquid biopsy tests completed via Guardant360. To meet model assumptions, ctDNA levels, measured by maximum variant allele frequency on each test, were transformed into logits. Due to the model’s hierarchal structure, an unconditional cubic spline model was fit first, producing an estimated response pattern for the cohort. Next, as patient-level results are of interest, the unconditional model was built upon by fitting a conditional model that incorporated covariates consisting of demographic, health status, and mortality information, which provided numerous patient-level response patterns. The best fitting conditional model was guided by Akaike’s information criteria. Results: Since model parameter estimates are uninterpretable, and because numerous patient-level projections are generated (each covariate value combination produces a unique projection), an R-Shiny application was developed to visually present and compare results in an intuitive interactive fashion. Additionally, to enhance the understanding of patient response patterns, velocity plots, which provides the instantaneous rate of change in ctDNA levels at different time points, are also provided. Conclusions: We demonstrate that the proposed method can successfully be applied to genomic data to describe and explore complex patient-level temporal ctDNA patterns while accounting for the impact of covariate values have on these patterns. We implemented the proposed methodology as a visualization tool that can be used in a wide variety of settings, ranging from hypothesis testing in clinical trials to patient monitoring. Results from the model can further our basic conceptualization of ctDNA dynamics and enhance our ability to integrate these results into targeted, patient centric, clinical decision-making. Citation Format: Christopher R. Pretz, Jiemin Liao, Leylah Drusbosky, Amar Das. Longitudinal assessment of circulating tumor DNA in patients with advanced colorectal cancer: A proposed general statistical framework and visualization tool [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2390.

Nexus between carbon emissions and local debt risk: Evidence from China's prefecture-level cities

Debt risk is an externality of carbon emissions in the greening transformation process. Based on panel data of 171 prefecture-level cities in China from 2012 to 2020, this article empirically analyzed the influence and mechanism of carbon emissions on local debt risk. The results can be concluded as follows: (1) Carbon emissions will significantly induce local debt risk. After considering the endogenous problem and serial robustness tests, the conclusions above are still valid. (2) Local debt risk itself has a cumulative expansion effect stimulate by carbon emissions. And carbon emissions will strengthen the depth of local debt risk with the increase of local debt risk. (3) The moderating impact of carbon emissions on local debt risk has heterogeneous characteristics, with different industrialization processes, developmental level of scientific and technological innovation, and corporate environmental management regulation. This article not only provides a new evidence for carbon emissions externality from local debt risk perspective, but also provides a useful reference for local governments to enhance debt risk governance, and orderly implement reduction action of carbon emissions.

Autoantibodes to GP210 are a metric for UDCA responses in primary biliary cholangitis

ObjectivesAntibodies to gp210 and sp100 are specific and unique anti-nuclear autoantibodies (ANAs) associated with primary biliary cholangitis (PBC). Importantly the presence of anti-gp210 and anti-sp100 responses is indicative of poor clinical outcomes. However, the utility of measuring titers of these antibodies remains unclear. Materials and methodsUsing the in-house purified gp210 (HSA108-C18) and sp100 (amino acid position 296–386), we quantitatively measured serum autoantibodies to gp210 and sp100 using chemiluminescence immunoassay (CLIA) in a very large cohort of 390 patients with PBC, including 259 cases with no prior ursodesoxycholic acid (UDCA) treatment and 131 cases with UDCA treatment. We also analyzed serial changes in anti-gp210 and anti-sp100 levels in 245 sequential samples from 88 patients. ResultsIn our cross-sectional analysis, we detected anti-gp210 immunoglobulin G (IgG) and anti-sp100 IgG autoantibodies in 129 out of 390 (33.1%) and 80 out of 390 (20.5%) PBC patients, respectively. Multivariate analysis revealed that serum IgG (st.β = 0.35, P = 0.003) and gamma-glutamyltransferase (GGT) (st.β = 0.23, P = 0.042) levels at baseline were independently associated with anti-gp210 concentrations. In serial testing, we observed significant fluctuations in anti-gp210 antibody levels. These fluctuations reflected responsiveness to UDCA therapy, particularly in anti-gp210-positive patients with initially lower concentrations in the stages of disease. ConclusionsOur study reflects that quantitative changes of anti-gp210 antibody are indicative of UDCA responses. There is a great need for newer metrics in PBC and we suggest that a more detailed and longer study of these unique ANAs is warranted.

Mapping Cognitive Trajectories and Detecting Early Dementia Using the Mini-Mental State Examination Cognitive Charts: Application to the French Three-City Cohort.

The Cognitive Quotient (QuoCo) classification algorithm monitoring decline on age- and education-adjusted Mini-Mental State Examination (MMSE)-derived cognitive charts has proved superior to the conventionally-used cut-off for identifying incident dementia; however, it remains to be tested in different settings. Data were drawn from the Three-City Cohort to 1) assess the screening accuracy of the QuoCo, and 2) compare its performance to that of serial MMSE tests applying different cut-offs. For the QuoCo, sensitivity was 74.2 (95% CI: 71.4-76.8) and specificity 84.1 (83.6-84.7) and for the MMSE < 24, 64.1 (61.1-67.0) and 94.8 (94.4-95.1), respectively; whereas overall accuracy and sensitivity was highest for MMSE cut-offs <25 and <26. User-friendly charts for mapping cognitive trajectories over visits with an alert for potentially 'abnormal' decline can be of practical use and encourage regular monitoring in primary care where the <24 cut-off is still widely used despite its poor sensitivity.

Sero-prevalence and risk factors associated with occurrence of anti-Brucella antibodies among slaughterhouse workers in Uganda.

Brucellosis is a febrile zoonosis occurring among high-risk groups such as livestock keepers and abattoir workers and is a public health priority in Uganda. The technical complexities of bacteriological and molecular methods make serological approaches the cornerstone of diagnosis of human brucellosis in resource limited settings. Therefore, proper application and interpretation of serological tests is central to achieve a correct diagnosis. We conducted a cross-sectional study to estimate the seroprevalence and factors associated with anti-Brucella antibodies among slaughterhouse workers processing ruminants and pigs in three regions of the country with serial testing using a combination of the Rose Bengal Test (RBT) and the BrucellaCapt test. An authorized clinician collected 543 blood samples from consenting abattoir workers as well as attribute medical and social demographic data. Univariable and multivariable logistic regression were used to determine factors associated with anti-Brucella sero-positivity. The sero-prevalence among ruminant slaughterhouse workers ranged from 7.3% (95% CI: 4.8-10.7) using BrucellaCapt to 9.0% (95% CI: 6.3-12.7) using RBT. Slaughterhouse workers from the Eastern regions (AOR = 9.84, 95%CI 2.27-69.2, p = 0.006) and those who graze animals for alternative income (AOR = 2.36, 95% CI: 1.91-6.63, p = 0.040) were at a higher risk of exposure to Brucella. Similarly, those who wore Personal Protective Equipment (AOR = 4.83, 95%CI:1.63-18.0, p = 0.009) and those who slaughter cattle (AOR = 2.12, 95%CI: 1.25-6.0, p = 0.006) were at a higher risk of exposure to Brucella. Those who slaughter small ruminants (AOR = 1.54, 95%CI: 1.32-4.01, p = 0.048) were also at a higher risk of exposure to Brucella. Our study demonstrates the combined practical application of the RBT and BrucellaCapt in the diagnosis of human brucellosis in endemic settings. Both pharmaceutical (e.g., routine testing and timely therapeutic intervention), and non-pharmaceutical (e.g., higher index of suspicion of brucellosis when investigating fevers of unknown origin and observation of strict abattoir hygiene) countermeasures should be considered for control of the disease in high-risk groups.

Combined balloon Eustachian tuboplasty/endoscopic sinus surgery for patients with chronic rhinosinusitis and Eustachian tube dysfunction.

To elucidate the role of balloon Eustachian tuboplasty (BET) in the management of chronic rhinosinusitis with obstructive Eustachian tube dysfunction (ETD), we evaluated the results of endoscopic sinus surgery (ESS) with and without BET in patients with chronic rhinosinusitis with obstructive ETD. This randomized controlled trial conducted in a single-institution tertiary care center setting included 50 patients diagnosed with primary chronic rhinosinusitis and obstructive ETD between July 2018 and June 2022. Twenty-five patients were prospectively enrolled for combined ESS/BET. The control group (25 patients) underwent ESS alone. Outcome measurements of the Sinonasal Outcome Test 22,modified Lund-Kennedy score, Eustachian Tube Dysfunction Questionnaire-7 (ETDQ-7), and serial Eustachian tube function test results were analyzed 3 months postoperatively. The improvement (12.60±6.50) in the ETDQ-7 score in the BET group was significantly higher than that in the control group (6.60±5.58). The ratio of improvement in the ETDQ-7 score was also significantly higher in the BET than in the control group (92%vs. 68%, p=0.034). Logistic regression analysis showed that performing BET (odds ratio [OR]: 5.41, 95% confidence interval [CI]: 1.02-28.79, p=0.048) and a low post-modified Lund-Kennedy score (OR: 0.15, 95% CI: 0.04-0.54, p=0.004) were significantly associated with ETDQ-7 score improvement. Combined BET/ESS could decrease otologic symptoms and improve Eustachian tube function. BET may be an appropriate adjunctive procedure for treating chronic rhinosinusitis with obstructive ETD.

Liposomal nanoformulations with trans-caryophyllene and caryophyllene oxide: do they have an inhibitory action on the efflux pumps NorA, Tet(K), MsrA, and MepA?

This study aimed to evaluate the antibacterial and inhibitory action of NorA, Tet(K), MsrA and MepA efflux pumps in S. aureus strains using the sesquiterpenes named trans-caryophyllene and caryophyllene oxide, both isolated and encapsulated in liposomes. The antibacterial and inhibitory action of these efflux pumps was evaluated through the serial microdilution test in 96-well microplates. Each sesquiterpene and liposome/sesquiterpene was combined with antibiotics and ethidium bromide (EtBr). The antibiotics named norfloxacin, tetracycline and erythromycin were used. The 1199 B, IS-58, RN4220 and K2068 S. aureus strains carrying NorA, Tet(K), MsrA and MepA, respectively, were tested. In the fluorescence measurement test, K2068 S. aureus was incubated with the sesquiterpenes and EtBr, and the fluorescence emission by EtBr was measured. The tested substances did not show direct antibacterial activity, with MIC >1024 μg/mL. Nonetheless, the isolated trans-caryophyllene and caryophyllene oxide reduced the MIC of antibiotics and EtBr, indicating inhibition of NorA, Tet(K) and MsrA. In the fluorescence test, these same sesquiterpenes increased fluorescence emission, indicating inhibition of MepA. Therefore, the sesquiterpenes named trans-caryophyllene and caryophyllene oxide did not show direct antibacterial action; however, in their isolated form, they showed possible inhibitory action on NorA, Tet(K), MsrA and MepA efflux pumps. They may also act in antibiotic potentiation. Further studies are needed to identify the mechanisms involved in antibiotic potentiation and efflux pump inhibitory action.

Usefulness of serial testing for the diagnosis of malaria in cases of fever upon return from travel.

When malaria is suspected in case of fever after travel in endemic areas, the current recommendation is to repeat the malaria test at 24-hour intervals, with up to two additional tests, as long as the test result is negative. A retrospective analysis was conducted to investigate the appropriateness of this recommendation by determining the proportion of tests with negative result at first and subsequently with a positive one at second or third attempt. A retrospective study was conducted at the Centre for Primary Care and Public Health, Lausanne, covering a period of 15years. All patients tested once for malaria were included. Testing included microscopy thick and thin films as well as malaria rapid diagnostic test used in combination. The main outcome measure was the proportion of patients with a first negative test result, subsequently positive on second or third test over the total patients with suspected malaria assessed. Demographic, travel, clinical, and laboratory variables were collected from patients' records to identify potential predictors of an initially negative and then positive test result. Four thousand nine hundred seventy-two patients were included. Of those, 4557 (91.7%) had definitive negative test results, and 415 (8.3%) had a positive result on the first test [332/415 (80%) Plasmodium falciparum, 40/415 (9.6%) P. vivax, 21/415 (5.1%) P. ovale, 12/415 (2.9%) P. vivax/ovale, 9/415 (2.2%) P. malariae and 1/415 (0.2%) P. knowlesi], and 3/4972 (0.06%) had a positive result on the second test after a first negative result, 1/4972(0.02%) had a positive test result after 2 negative results, all with P. falciparum. One of the four patients that were positive after their initial negative test was pregnant. The very small number of patients with an initially negative test result and secondarily positive did not allow for risk factor analysis. The current recommendation of serial malaria testing is not supported by the present study, a fortiori for those who do not present with a strong clinical or laboratory predictor of malaria.

Retrospective evaluation of leflunomide as an adjunctive therapy in dogs with non-associative immune-mediated thrombocytopenia: 20 cases (2008-2021).

To describe leflunomide as an adjunctive therapy in the treatment of non-associative immune-mediated thrombocytopenia. A retrospective study of dogs with a diagnosis of non-associative immune-mediated thrombocytopenia treated with leflunomide March 2008 to September 2021 was conducted. Data collected included signalment, clinical signs, physical examination findings and diagnostic testing performed. Medications administered, duration of hospital stay, time to platelet concentration >150×109/L and adverse events during leflunomide therapy were recorded. Relapses within a year of diagnosis were reported. A total of 20 client-owned dogs met inclusion criteria. Nineteen of 20 dogs (95%) achieved a platelet concentration >150×109/L with leflunomide and prednisone combination therapy and four dogs (21.1%) relapsed during treatment or shortly after treatment. Adverse effects included diarrhoea (n=5), mild lymphopenia (n=9) and mild intermittent anaemia (n=1). A single dog developed hepatotoxicity presumed to be secondary to leflunomide therapy that resolved after drug discontinuation. One dog was treated for aspiration pneumonia during treatment. Two dogs were euthanased while receiving leflunomide. Length of hospitalisation, time to platelet recovery, treatment response and relapse rate were comparable with alternative treatment protocols. Most adverse effects did not require leflunomide dose adjustment; however, two dogs died while undergoing leflunomide treatment and there is compelling evidence that one of these dogs experienced fatal infection secondary to immune-suppression. Hepatotoxicity remains a known complication of leflunomide treatment and serial biochemistry testing is recommended.

Comparing urine point-of-care tests to screen preeclampsia: Congo-red dot paper test versus dipstick urinalysis.

To compare the urine Congo-red dot paper test (CRD) with dipstick urinalysis to screen preeclampsia (PE). A total of 409 paired spot urine samples were obtained prospectively from women with suspected pre-eclampsia attending for routine hospital visits. Congo-red dot paper test and dipstick urinalysis were examined and compared to screen pre-eclampsia. The agreement between the two urinary test is modest (kappa coefficient=0.28, 95% CI 0.14-0.42). The specificity of CRD was higher than urinalysis (97.4% vs. 90.4%, p<.001). Urinalysis performed better in sensitivity (77.3% vs. 40.9%, p=.04) and the area under the receiver operating characteristic curves (AUC) (0.84 [95% CI 0.74-0.94] vs. 0.69 [95% CI 0.55-0.83], p=.04) than CRD, respectively. The sensitivity, specificity, AUC of the parallel test of them is 86.4% (64.0%-96.4%), 89.1% (85.5%-92.0%), and 0.88 (95% CI 0.79-0.96). And the serial test is 31.8% (14.7%-54.9%), 98.7% (96.8%-99.5%), 0.65 (95% CI 0.51-0.79), accordingly. The urinalysis is a better diagnosing test for preeclampsia. CRD could aid in the diagnosis of patients with preeclampsia. Combined the two tests in suspected patients may further improve the performance in the diagnosis of preeclampsia. Further study need to be made for its potential clinical practice.

Do serial troponins predict the need for cardiac evaluation in trauma patients after ground-level fall?

PurposeTroponin T levels are routinely checked in trauma patients after experiencing a ground-level fall to identify potential cardiac causes of syncope. An elevated initial troponin prompts serial testing until the...

The combination of high-frequency QRS and ST-segment alterations during exercise stress tests enhanced the diagnostic efficacy for coronary artery disease.

High-frequency QRS (HF-QRS) manifests as a novel adjunct electrocardiographic marker with potential utility in coronary artery disease (CAD) detection. We hypothesize that HF-QRS analysis may be superior to conventional ST-segment analysis in detecting CAD, and the combination of these two analyses in the exercise stress test may enhance the diagnostic efficacy for CAD. The study incorporated a sample of 157 patients (mean age 62 9 years) referred for nonemergent angiography. Before angiography, patients underwent exercise stress testing utilizing an upright bicycle. High-resolution electrocardiogram (ECG) data were collected during the exercise test, facilitating both HF-QRS and conventional ST-segment analyses. The diagnostic efficacy of HF-QRS and ST-segment analysis were compared, utilizing angiographic outcomes as the gold standard. The study design integrated HF-QRS analysis and ST-segment analysis via sequential and concurrent testing protocols. In terms of CAD detection, HF-QRS analysis displayed superior sensitivity compared to conventional ST-segment analysis (63% vs. 37%, p = .002). The serial test significantly increased specificity from 79% to 97% (p = .002) compared to ST-deviation analysis alone. It showed a markedly low sensitivity of 26%. The parallel test significantly increased sensitivity from 37% to 77% (p < .001), while retaining a moderate level of specificity of 51%. The quantity of ECG leads exhibiting a positive HF-QRS response demonstrated a correlation with the severity of CAD (p < .001). HF-QRS analysis exhibited superior sensitivity in detecting angiographically confirmed CAD relative to conventional ST-segment analysis. Moreover, the combination of HF-QRS and ST-segment alterations during exercise stress test enhanced the diagnostic efficacy for CAD.