Long-term findings on working memory neural dynamics in healthcare workers after mild COVID-19.

OBJECTIVE: Understanding the long-term impact of Coronavirus Disease 2019 (COVID-19) on cognitive function, even in mild cases, is critical to the well-being of individuals, especially for healthcare workers who are at increased risk of exposure to the virus. To the best of our knowledge, the electrophysiological activity underlying cognitive functioning has not yet been explored. METHODS: Seventy-seven healthcare workers took part in the study (43 with mild infection about one year before the study and 34 uninfected). To assess cognitive status, event-related potentials (ERPs) and behavioural responses were recorded while participants performed a working memory task. RESULTS: COVID-19 participants exhibited a distinct neural pattern with lower parieto-occipital N1 amplitudes and higher frontal P2 amplitudes as compared to non-infected healthcare workers. We found no behavioural differences (reaction times and error rates) in working memory functioning between groups. CONCLUSIONS: This neural pattern suggests the presence of a decrement of processing resources linked to the encoding of sensory information (N1), followed by the enhanced of the P2 response which could be interpreted as the activation of compensation mechanism in COVID-19 participants. SIGNIFICANCE: The current findings point out that ERPs could serve as valuable neural indices for detecting distinctive patterns in working memory functioning of COVID-19 participants, even in mild cases. However, further research is required to precisely ascertain the long-term cognitive effects of COVID-19 beyond one-year post-infection.

Leptospirosis infections among hospital patients, Sarawak, Malaysia.

BACKGROUND: Leptospirosis diagnoses have increased in Sarawak, Malaysia in recent years. METHODS: To better understand the burden of disease and associated risk factors, we evaluated 147 patients presenting with clinical leptospirosis to local hospitals in Sarawak, Malaysia for the presence of Leptospira and associated antibodies. Sera and urine specimens collected during the acute illness phase were assessed via a commercially available rapid diagnostic test (Leptorapide, Linnodee Ltd., Antrim, Northern Ireland), an ELISA IgM assay (Leptospira IgM ELISA, PanBio, Queensland, Australia) and a pan-Leptospira real-time PCR (qPCR) assay to estimate disease prevalence and diagnostic accuracy of each method. Microagglutination testing was performed on a subset of samples. RESULTS: Overall, 45 out of 147 patients (30.6%) showed evidence of leptospires through qPCR in either one or both sera (20 patients) or urine (33 patients), and an additional ten (6.8%) were considered positive through serological testing, for an overall prevalence of 37.4% within the study population. However, each diagnostic method individually yielded disparate prevalence estimates: rapid test 42.2% for sera and 30.5% for urine, ELISA 15.0% for sera, qPCR 13.8% for sera and 23.4% for urine. Molecular characterization of a subset of positive samples by conventional PCR identified the bacterial species as Leptospira interrogans in 4 specimens. A multivariate risk factor analysis for the outcome of leptospirosis identified having completed primary school (OR = 2.5; 95 CI% 1.0-6.4) and weekly clothes-washing in local rivers (OR = 10.6; 95 CI% 1.4-214.8) with increased likelihood of leptospirosis when compared with those who had not. CONCLUSION: Overall, the data suggest a relatively high prevalence of leptospirosis in the study population. The low sensitivities of the rapid diagnostic test and ELISA assay against qPCR highlight a need for better screening tools.

Panspecies molecular assays detect viral pathogens missed by real-time PCR/reverse-transcriptase PCR among pneumonia patients, Sarawak, Malaysia.

BACKGROUND: In a year-long pneumonia etiology study conducted June 2017 to May 2018 in Sarawak, Malaysia, 599 patients' nasopharyngeal swab specimens were studied with real-time polymerase chain reaction (rPCR)/ reverse-transcription (rRT-PCR) assays for respiratory pathogens known to contribute to the high burden of lower respiratory tract infections. The study team sought to compare real-time assay results with panspecies conventional molecular diagnostics to compare sensitivities and learn if novel viruses had been missed. METHODS: Specimens were studied for evidence of adenovirus (AdV), enterovirus (EV) and coronavirus (CoV) with panspecies gel-based nested PCR/RT-PCR assays. Gene sequences of specimens positive by panspecies assays were sequenced and studied with the NCBI Basic Local Alignment Search Tool software. RESULTS: There was considerable discordance between real-time and conventional molecular methods. The real-time AdV assay found a positivity of 10.4%; however, the AdV panspecies assay detected a positivity of 12.4% and the conventional AdV-Hexon assay detected a positivity of 19.6%. The CoV and EV panspecies assays similarly detected more positive specimens than the real-time assays, with a positivity of 7.8% by the CoV panspecies assay versus 4.2% by rRT-PCR, and 8.0% by the EV panspecies assay versus 1.0% by rRT-PCR. We were not able to ascertain virus viability in this setting. While most discordance was likely due to assay sensitivity for previously described human viruses, two novel, possible zoonotic AdV were detected. CONCLUSIONS: The observed differences in the two modes of amplification suggest that where a problem with sensitivity is suspected, real-time assay results might be supplemented with panspecies conventional PCR/RT-PCR assays.

Correlation of 2-year SRS-22r and ODI patient-reported outcomes with 5-year patient-reported outcomes after complex spinal fusion: a 5-year single-institution study of 118 patients.

OBJECTIVE: Patient-reported outcomes (PROs) are often measured up to 2 years after surgery; however, prospective collection of longitudinal outcomes for 5 years postoperatively can be challenging due to lack of patient follow-up. The aim of this study was to determine whether PROs collected at 2-year follow-up accurately predict long-term PROs 5 years after complex spinal fusion (≥ 5 levels). METHODS: This was an ambispective study of 118 adult patients (≥ 18 years old) undergoing ≥ 5-level spinal arthrodesis to the sacrum with iliac fixation from January 2002 to December 2011. Patient demographics and radiographic parameters as well as intraoperative variables were collected. PRO instruments (Scoliosis Research Society [SRS]-22r function, self-image, mental health, pain, and Oswestry Disability Index [ODI]) were completed before surgery then at 2 and 5 years after surgery. Primary outcome investigated in this study was the correlation between SRS-22r domains and ODI collected at 2- and 5-year follow-up. RESULTS: Of the 118 patients, 111 patients had baseline PROs, 105 patients had 2-year follow-up data, and 91 patients had 5-year follow-up PRO data with 72% undergoing revision surgery. The average pre- and postoperative major coronal curve Cobb angles for the cohort were 32.1° ± 23.7° and 19.8° ± 19.3°, respectively. There was a strong correlation between 2- and 5-year ODI (r2 = 0.80, p < 0.001) and between 2- and 5-year SRS-22r domains, including function (r2 = 0.79, p < 0.001), self-image (r2 = 0.82, p < 0.001), mental health (r2 = 0.77, p < 0.001), and pain (r2 = 0.79, p < 0.001). Of the PROs, ODI showed the greatest absolute change from baseline to 2- and 5-year follow-up (2-year Δ 17.6 ± 15.9; 5-year Δ 16.5 ± 19.9) followed by SRS-22r self-image (2-year Δ 1.4 ± 0.96; 5-year Δ 1.3 ± 1.0), pain (2-year Δ 0.94 ± 0.97; 5-year Δ 0.80 ± 1.0), function (2-year Δ 0.60 ± 0.62; 5-year Δ 0.49 ± 0.79), and mental health (2-year Δ 0.49 ± 0.77; 5-year Δ 0.38 ± 0.84). CONCLUSIONS: Patient-reported outcomes collected at 2-year follow-up may accurately predict long-term PROs (5-year follow-up).

The Impact of Chronic Kidney Disease on Postoperative Outcomes in Patients Undergoing Lumbar Decompression and Fusion.

OBJECTIVE: To determine whether preoperative chronic kidney disease (CKD) is associated with inferior perioperative outcomes in patients undergoing lumbar arthrodesis. METHODS: Medical records of 293 adult (≥18 years old) patients with spine deformity undergoing elective lumbar spine decompression and fusion at a major academic institution from 2006 to 2015 were reviewed. We identified 18 (6.1%) patients with a clinical diagnosis of CKD (CKD group, n = 18; no-CKD group, n = 275). Patient demographics, comorbidities, and intraoperative and postoperative complication rates were collected for each patient. The primary endpoint was incidence of postoperative complications. RESULTS: Patient demographics, including age, sex, and body mass index, and comorbidities were similar between cohorts. The CKD group had a significantly higher prevalence of hypertension, hyperlipidemia, and anemia compared with the no-CKD group. Median number of fusion levels, length of surgery, and estimated blood loss were similar between both cohorts. Postoperative complication profile was significantly different between the cohorts, with the CKD group having a significantly higher proportion of patients transferred to the intensive care unit (52.9% vs. 29.3%, P = 0.04) with episodes of delirium (27.8% vs. 8.4%, P = 0.007), urinary tract infection (27.8% vs. 6.9%, P = 0.0002), and deep vein thrombosis (5.6% vs. 0.4%, P = 0.01). Although not significant, the CKD group had a 2-fold higher rate of 30-day readmissions compared with the no-CKD group (CKD group: 27.8% vs. no-CKD group: 12.7%, P = 0.07). CONCLUSIONS: Our study suggests that patients with CKD may be more likely to develop perioperative complications after lumbar arthrodesis. Future studies are necessary to corroborate our findings.

Interactions of the Metalloregulatory Protein SloR from Streptococcus mutans with Its Metal Ion Effectors and DNA Binding Site.

UNLABELLED: Streptococcus mutans is the causative agent of dental caries, a significant concern for human health, and therefore an attractive target for therapeutics development. Previous work in our laboratory has identified a homodimeric, manganese-dependent repressor protein, SloR, as an important regulator of cariogenesis and has used site-directed mutagenesis to map functions to specific regions of the protein. Here we extend those studies to better understand the structural interaction between SloR and its operator and its effector metal ions. The results of DNase I assays indicate that SloR protects a 42-bp region of DNA that overlaps the sloABC promoter on the S. mutans UA159 chromosome, while electrophoretic mobility shift and solution binding assays indicate that each of two SloR dimers binds to this region. Real-time semiquantitative reverse transcriptase PCR (real-time semi-qRT-PCR) experiments were used to determine the individual base pairs that contribute to SloR-DNA binding specificity. Solution studies indicate that Mn(2+) is better than Zn(2+) at specifically activating SloR to bind DNA, and yet the 2.8-Å resolved crystal structure of SloR bound to Zn(2+) provides insight into the means by which selective activation by Mn(2+) may be achieved and into how SloR may form specific interactions with its operator. Taken together, these experimental observations are significant because they can inform rational drug design aimed at alleviating and/or preventing S. mutans-induced caries formation. IMPORTANCE: This report focuses on investigating the SloR protein as a regulator of essential metal ion transport and virulence gene expression in the oral pathogen Streptococcus mutans and on revealing the details of SloR binding to its metal ion effectors and binding to DNA that together facilitate this expression. We used molecular and biochemical approaches to characterize the interaction of SloR with Mn(2+) and with its SloR recognition element to gain a clearer picture of the regulatory networks that optimize SloR-mediated metal ion homeostasis and virulence gene expression in S. mutans. These experiments can have a significant impact on caries treatment and/or prevention by revealing the S. mutans SloR-DNA binding interface as an appropriate target for the development of novel therapeutic interventions.