Nevin Manimala

Circ Res. 2022 Jun 29:101161CIRCRESAHA122321116. doi: 10.1161/CIRCRESAHA.122.321116. Online ahead of print.

ABSTRACT

BACKGROUND: CD (cluster of differentiation) 4⁺ T-cell responses to APOB (apolipoprotein B) are well characterized in atherosclerotic mice and detectable in humans. CD4⁺ T cells recognize antigenic peptides displayed on highly polymorphic HLA (human leukocyte antigen)-II. Immunogenicity of individual APOB peptides is largely unknown in humans. Only 1 HLA-II-restricted epitope was validated using the DRB1*07:01-APOB_3036-3050 tetramer. We hypothesized that human APOB may contain discrete immunodominant CD4⁺ T-cell epitopes that trigger atherosclerosis-related autoimmune responses in donors with diverse HLA alleles.

METHODS: We selected 20 APOB-derived peptides (APOB₂₀) from an in silico screen and experimentally validated binding to the most commonly occurring human HLA-II alleles. We optimized a restimulation-based workflow to evaluate antigenicity of multiple candidate peptides in HLA-typed donors. This included activation-induced marker assay, intracellular cytokine staining, IFNγ (interferon gamma) enzyme-linked immunospot and cytometric bead array. High-throughput sequencing delineated TCR (T-cell receptor) clonalities of APOB-reactive CD4⁺ T cells.

RESULTS: Using stringent positive, negative, and crossover stimulation controls, we confirmed specificity of expansion-based protocols to detect CD4⁺ T cytokine responses to APOB₂₀ pool. Ex vivo assessment of AIM⁺CD4⁺ T cells revealed statistically significant autoimmune response to APOB₂₀ but not to a ubiquitously expressed negative control protein, actin. Resolution of CD4⁺ T responses to the level of individual peptides using IFNγ enzyme-linked immunospot led to the discovery of 6 immunodominant epitopes (APOB₆) that triggered robust CD4⁺ T activation in most donors. APOB₆-specific responding CD4⁺ T cells were enriched in unique expanded TCR clonotypes and preferentially expressed memory markers. Cytometric bead array analysis detected APOB₆-induced secretion of both proinflammatory and regulatory cytokines. In clinical samples from patients with angiographically verified coronary artery disease, APOB₆ stimulation induced higher activation and memory phenotypes and augmented secretion of proinflammatory cytokines TNF (tumor necrosis factor) and IFNγ, compared with patients with low coronary artery disease.

CONCLUSIONS: Using 3 cohorts, each with ≈20 donors, we discovered and validated 6 immunodominant, HLA-II-restricted APOB epitopes. Immune response to these APOB epitopes correlated with coronary artery disease severity.

PMID:35766025 | DOI:10.1161/CIRCRESAHA.122.321116

Clin Exp Rheumatol. 2022 Jun 28. doi: 10.55563/clinexprheumatol/jx4x0b. Online ahead of print.

NO ABSTRACT

PMID:35765998 | DOI:10.55563/clinexprheumatol/jx4x0b

Ann Lab Med. 2022 Nov 1;42(6):630-637. doi: 10.3343/alm.2022.42.6.630.

ABSTRACT

BACKGROUND: The top-down (TD) approach using internal quality control (IQC) data is regarded a practical method for estimating measurement uncertainty (MU) in clinical laboratories. We estimated the MU of 14 clinical chemistry analytes using the TD approach and evaluated the effect of lot changes on the MU.

METHODS: MU values were estimated using subgrouping by reagent lot changes or using the data as a whole, and both methods were compared. Reagent lot change was simulated using randomly generated data, and the mean values and MU for two IQC datasets (different QC material lots) were compared using statistical methods.

RESULTS: All MU values calculated using subgrouping were lower than the total values; however, the average differences were minimal. The simulation showed that the greater the increase in the extent of the average shift, the larger the difference in MU. In IQC data comparison, the mean values and MU exhibited statistically significant differences for most analytes. The MU calculation methods gave rise to minimal differences, suggesting that IQC data in clinical laboratories show no significant shift. However, the simulation results demonstrated that notable differences in the MU can arise from significant variations in IQC results before and after a reagent lot change. Additionally, IQC material lots should be treated separately when IQC data are collected for MU estimation.

CONCLUSIONS: Lot changes in IQC data are a key factor affecting MU estimation and should not be overlooked during MU estimation.

PMID:35765871 | DOI:10.3343/alm.2022.42.6.630

Water Environ Res. 2022 Jul;94(7):e10750. doi: 10.1002/wer.10750.

ABSTRACT

Municipal water resource recovery facilities (WRRFs) are important sources of antibiotic-resistant bacteria and genes (ARB and ARGs). In this study, antibiotic-resistant total heterotrophic bacteria (THB_R ) counts (CFU/ml) cultivated from influent, effluent of activated sludge process, and outflow of disinfection unit of an urban WRRF were investigated for the presence of 16, 32, 64, and 128 μg/ml of nine antibiotics. The isolates of Pseudomonas spp., Acinetobacter spp., and Escherichia coli obtained from effluent of activated sludge process were subjected for molecular identification by detecting the 16S rRNA gene sequences. Additionally, using the polymerase chain reaction method (PCR), the isolates were investigated for the presence of bla_SHV , bla_TEM , bla_CTX-M , bla_VIM , sul1, and qnrS genes. According to the results, the abundance of THB_R counts was not significantly reduced by the biological treatment except for cefixime and sulfamethoxazole; it also increased for some antibiotics after disinfection unit. The average removal efficiency of THB_R resistant to ciprofloxacin, sulfamethoxazole, and ceftazidime were 7.9 ± 1.7%, 41.8 ± 2.1%, and 14.4 ± 6.2%, respectively. Also, all the tested isolates were resistant to at least four antibiotics. For all antibiotics, the resistance ratio (THB_R /THB) significantly increased in the effluent and after chlorination unit. Among 12 resistant isolates, bla_TEM and sul1 genes were the most frequently detected ones involved in 92% and 83% of the isolates, respectively. Both bla_TEM and sul1 genes were found in 100% of E. coli, and 83% and 67% of Pseudomonas spp. isolates, respectively. Further efforts are necessary to limit the transmission of ARB and ARGs from WRRFs into the environment and prevent human health threats. PRACTITIONER POINTS: The ratio of resistance significantly increased after biological treatment. Up to 40% of heterotrophic bacteria in the effluent was antibiotic resistant. bla_TEM and sul1 genes were more prevalent (92%) in all isolates of bacteria. Both bla_TEM and sul1 genes were found in 100% of E. coli isolates. Pseudomonas spp. holds bla_TEM and sul1 genes in 83% and 67% of isolates, respectively.

PMID:35765862 | DOI:10.1002/wer.10750

Ther Apher Dial. 2022 Jun 29. doi: 10.1111/1744-9987.13906. Online ahead of print.

ABSTRACT

INTRODUCTION: Plasmapheresis is a well-recognized treatment for autoimmune neurological diseases in Japan. However, the practice varies depending on the facility, and the actual treatment conditions are unclear.

METHODS: To clarify real-world conditions, a prospective observational study was conducted on patients with neurological diseases who were scheduled to receive plasmapheresis. A dataset was analyzed that included 887 treatments from 210 patients with myasthenia gravis (MG), multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and other diseases for 82, 30, 24, and 74 patients, respectively.

RESULTS: The types of plasmapheresis performed included immunoadsorption plasmapheresis, plasma exchange, and double filtration plasmapheresis with 620, 213, and 54 treatments, respectively. Approximately 60% of the treatments were performed using peripheral blood access alone. Non-serious adverse events were observed in ten patients.

CONCLUSIONS: A statistically significant improvement was observed after plasmapheresis in patients with MG, MS, and NMOSD. These were evaluated using the modified Rankin Scale.

PMID:35765859 | DOI:10.1111/1744-9987.13906

Anaesth Intensive Care. 2022 Jun 29:310057X221092455. doi: 10.1177/0310057X221092455. Online ahead of print.

ABSTRACT

The COVID-19 pandemic has strained surgical systems worldwide and placed healthcare providers at risk in their workplace. To protect surgical care providers caring for patients with COVID-19, in May 2020 we developed a COVID-19 Surgical Patient Checklist (C19 SPC), including online training materials, to accompany the World Health Organization Surgical Safety Checklist. In October 2020, an online survey was conducted via partner and social media networks to understand perioperative clinicians’ intraoperative practice and perceptions of safety while caring for COVID-19 positive patients and gain feedback on the utility of C19 SPC. Descriptive statistics were used to characterise responses by World Bank income classification. Qualitative analysis was performed to describe respondents’ perceptions of C19 SPC and recommended modifications. Respondents included 539 perioperative clinicians from 63 countries. One-third of respondents reported feeling unsafe in their workplace due to COVID-19 with significantly higher proportions in low (39.8%) and lower-middle (33.9%) than higher income countries (15.6%). The most cited concern was the risk of COVID-19 transmission to self, colleagues and family. A large proportion of respondents (65.3%) reported that they had not used C19 SPC, yet 83.8% of these respondents felt it would be useful. Of those who reported that they had used C19 SPC, 62.0% stated feeling safer in the workplace because of its use. Based on survey results, modifications were incorporated into a subsequent version. Our survey findings suggest that perioperative clinicians report feeling unsafe at work during the COVID-19 pandemic. In addition, adjunct tools such as the C19 SPC can help to improve perceived safety.

PMID:35765829 | DOI:10.1177/0310057X221092455

Twin Res Hum Genet. 2022 Jun 29:1-7. doi: 10.1017/thg.2022.19. Online ahead of print.

ABSTRACT

In this study, we analyzed the estimated frequency of monozygotic (MZ) and dizygotic (DZ) spontaneous twins in Lombardy during the period 2007-2017. This is a population-based study using the regional healthcare utilization databases of the Lombardy Region. The total number of spontaneous twin deliveries, in separate strata of like and unlike sex, was obtained. Moreover, estimates of DZ and MZ twin births were calculated using Weinberg’s method. The standardized rates (SRs), adjusted for maternal age, of DZ and MZ twin births were computed according to calendar period. The twinning rates were calculated among strata of parity and maternal age. Finally, DZ:MZ ratio was calculated. Among the 734,278 spontaneous deliveries, 9176 (12.5 out of 1000 births) couples of twins were identified. In the three periods considered (i.e. 2007-2010, 2011-2014 and 2015-2017), no trend in the SRs of MZ twins was observed, respectively 0.41 (95% CI [0.40, 0.43]), 0.43 (95% CI [0.42, 0.45]) and 0.43 (95% CI[0.42, 0.45]). Differently, a slightly decreasing trend was observed in DZ twins SRs, respectively 0.87 (95% CI [0.84, 0.89]), 0.81 (95% CI [0.79, 0.83]), and 0.78 (95% CI [0.76, 0.80]). As concerns parity and maternal age, the rate of DZ twin births was consistently higher in nulliparae women aged 35 years or more. In our cohort, despite the increase of maternal age, a decline of spontaneous twin births emerged, especially due to the downward trend of DZ twins.

PMID:35765814 | DOI:10.1017/thg.2022.19

Biol Lett. 2022 Jun;18(6):20220183. doi: 10.1098/rsbl.2022.0183. Epub 2022 Jun 29.

ABSTRACT

Biodiversity is measured from various perspectives. One of them, functional diversity, quantifies the heterogeneity in species traits and roles in an ecosystem. One important aspect of species roles is their interactions with other species, i.e. their network role. We therefore investigate here functional diversity from the network perspective. Species differ in their network positions in a food web, having different interaction patterns. We developed a measure for quantifying the diversity in species interaction patterns in a food web. We examined the relationship between interaction diversity and several global network properties for 92 food webs. Our results showed that high interaction diversity occurs in sparsely connected and less cohesive food webs. High interaction diversity also occurred in food webs with more clusters and high network modularity. We also quantified several conventional functional diversity indices and demonstrate that they show little or no correlation with interaction diversity. Our proposed diversity index therefore provides a measure complementary to current concepts of functional diversity.

PMID:35765809 | DOI:10.1098/rsbl.2022.0183

J Korean Neurosurg Soc. 2022 Jun 29. doi: 10.3340/jkns.2021.0168. Online ahead of print.

ABSTRACT

OBJECTIVE: Although full-endoscopic lumbar interbody fusion (Endo-LIF) has been tried as the latest alternative technique to minimally invasive transforaminal lumbar interobody fusion (MIS-TLIF) since mid-2010, the evidence is still lacking. We compared the clinical outcome and safety of Endo-LIF to MIS-TLIF for lumbar degenerative disease.

METHODS: We systematically searched electronic databases, including PubMed, EMBASE, and Cochrane Library to find literature comparing Endo-LIF to MIS-TLIF. The results retrieved were last updated on December 11, 2020. The perioperative outcome included the operation time, blood loss, complication, and hospital stay. The clinical outcomes included Visual analog scale (VAS) of low back pain and leg pain and Oswestry disability index (ODI), and the radiological outcome included pseudoarthosis rate with 12-month minimum follow-up.

RESULTS: Four retrospective observational studies and one prospective observational study comprising 423 patients (183 Endo-LIF and 241 MIS-TLIF) were included, and the pooled data analysis revealed low heterogeneity between studies in our review. Baseline characteristics including age and sex were not different between the two groups. Operation time was significantly longer in Endo- LIF (mean difference [MD], 23.220 minutes; 95% confidence interval [CI], 10.669-35.771; p=0.001). However, Endo-LIF resulted in less perioperative blood loss (MD, -144.710 mL; 95% CI, 247.941-41.478; p=0.023). Although VAS back pain at final (MD, -0.120; p=0.586), leg pain within 2 weeks (MD, 0.005; p=0.293), VAS leg pain at final (MD, 0.099; p=0.099), ODI at final (MD, 0.141; p=0.093) were not different, VAS back pain within 2 weeks was more favorable in the Endo-LIF (MD, -1.538; 95% CI, -2.044 to -1.032; p<0.001). On the other hand, no statistically significant group difference in complication rate (relative risk [RR], 0.709; p=0.774), hospital stay (MD, -2.399; p=0.151), and pseudoarthrosis rate (RR, 1.284; p=0.736) were found.

CONCLUSION: Relative to MIS-TLIF, immediate outcomes were favorable in Endo-LIF in terms of blood loss and immediate VAS back pain, although complication rate, mid-term clinical outcomes, and fusion rate were not different. However, the challenges for Endo-LIF include longer operation time which means a difficult learning curve and limited surgical indication which means patient selection bias. Larger-scale, well-designed study with long-term follow-up and randomized controlled trials are needed to confirm and update the results of this systematic review.

PMID:35765801 | DOI:10.3340/jkns.2021.0168

Orthop Surg. 2022 Jun 28. doi: 10.1111/os.13203. Online ahead of print.

ABSTRACT

OBJECTIVE: To study the epidemiological correlation and drug resistance of external factors of infection caused by open injury of limbs to pathogens.

METHODS: This experiment is a retrospective study. We took the geographical location and climate of Nanchang, Jiangxi Province, China as the background, analyzed 2017 strains of pathogens from 1589 patients with limb trauma infection in a University Affiliated Hospital from 2012 to 2017. Patients were divided into three groups according to the type of incision: I, In-hospital infection of clean limb incision, II, In-hospital infection with open injury, III, Community infection with open injury of the limb. Groups II and Groups III were divided into six subgroups according to the causes of trauma, including: accidents from non-motor vehicles, machinery, cutting/piercing, pedestrian injuries, struck by/against, pedal cycles, and other injuries. We found eight common pathogens of orthopedic infection, which were mainly divided into Gram-positive bacteria (G+, mainly including Staphylococcus) and Gram-negative bacteria (G-, mainly Enterobacteriaceae). The relationship between main pathogens and damage mechanism, apparent temperature and relative humidity was discussed in this study. SPSS v22.0 was used for statistical analysis of the data. Friedman’s two-way ANOVA was used to analyze the difference between the injury mechanism and incidence of pathogenic bacteria. Linear regression was used to determine the trend between the incidence of major pathogens and seasonal temperature and humidity. The level of significance was set as P < 0.05.

RESULTS: There was no significant difference in the distribution of pathogens between Groups II and Groups III (P>0.05). The drug resistance of Groups III was significantly higher than that of Groups II and Groups I. G+ bacteria were resistant to cephalosporin, ceftriaxone and other cephalosporins and erythromycin and other macrolides. They were sensitive to vancomycin and linezolid. G- were resistant to the first- and the second-generation cephalosporins, including cefotetan and cefazolin, and ampicillin and other penicillins, while they were sensitive to third-generation cephalosporins, such as ceftazidime, as well as to levofloxacin and other quinolones, meropenem, and other beta-lactamases. The correlation between the injury mechanism and infection of pathogenic bacteria was not significant. The monthly average apparent temperature and relative humidity were correlated with the infection rate of pathogenic bacteria.

CONCLUSION: In open injury of extremities, apparent temperature and relative humidity is an important risk factor for infection by pathogenic bacteria and the drug resistance of pathogenic bacteria in out-of-hospital infection was lower than that of hospital infection.

PMID:35765776 | DOI:10.1111/os.13203