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In his book The Deadly Rise of Anti-Science: a Scientist\'s Warning, Peter Hotez, Dean for the National School of Tropical Medicine at Baylor College of Medicine Houston, TX, USA, and an internationally acclaimed researcher known for defending vaccines and combating anti-science, explores how anti-science and anti-vaccination rhetoric are on the rise. He has created an illustrative narrative combining his normative experience as a scientist coupled with a wealth of literature and informative visualizations.

by The PLOS ONE Editors …

by Travis W. Brown, Geun W. Park, Beth Wittry, Leslie Barclay, Margaret Person, Boris Relja, Scott Daly, Preeti Chhabra, Erin Kincaid, Jona Johnson, Ausaf Ahmad, Owen Herzegh, Jan Vinjé, Jennifer Murphy While the COVID-19 pandemic has had a detrimental impact on many businesses worldwide, essential businesses, such as grocery stores, continued to operate despite potential disease transmission. Although the principal mode by which people are infected with SARS-CoV-2, the virus that causes COVID-19, is through exposure to respiratory droplets and very small particles carrying infectious virus, contaminated surfaces might play a role in transmission. We collected swab samples from frequently touched surfaces, including grocery carts, touchscreen monitors, credit card keypads, pharmacy counters, self-service food utensils, and refrigerator and freezer handles, in two metro-Atlanta grocery stores over the course of two sampling events in March 2021. Of the 260 swab samples collected, 6 (2.3%) samples were positive for SARS-CoV-2 RNA by reverse transcriptase quantitative polymerase chain reaction. Positive samples were collected from pharmacy (12.0% [3/25] samples), refrigerator/freezer aisles (2.5% [1/39] samples), and self-service food court (5.0% [2/40] samples) areas. Table/counter edge and underside surfaces represented 33% (2/6) of positive samples. These data suggest that risk of exposure to SARS-CoV-2 from frequently touched surfaces in grocery store settings is likely low; however, more frequent cleaning of surfaces in pharmacy and self-service food courts might be warranted.

by Toshihiro Takahashi, Tomohiko Ai, Kaori Saito, Shuko Nojiri, Maika Takahashi, Gene Igawa, Takamasa Yamamoto, Abdullah Khasawneh, Faith Jessica Paran, Satomi Takei, Yuki Horiuchi, Takayuki Kanno, Minoru Tobiume, Makoto Hiki, Mitsuru Wakita, Takashi Miida, Atsushi Okuzawa, Tadaki Suzuki, Kazuhisa Takahashi, Toshio Naito, Yoko Tabe The COVID-19 antibody test was developed to investigate the humoral immune response to SARS-CoV-2 infection. In this study, we examined whether S antibody titers measured using the anti-SARS-CoV-2 IgG II Quant assay (S-IgG), a high-throughput test method, reflects the neutralizing capacity acquired after SARS-CoV-2 infection or vaccination. To assess the antibody dynamics and neutralizing potency, we utilized a total of 457 serum samples from 253 individuals: 325 samples from 128 COVID-19 patients including 136 samples from 29 severe/critical cases (Group S), 155 samples from 71 mild/moderate cases (Group M), and 132 samples from 132 health care workers (HCWs) who have received 2 doses of the BNT162b2 vaccinations. The authentic virus neutralization assay, the surrogate virus neutralizing antibody test (sVNT), and the Anti-N SARS-CoV-2 IgG assay (N-IgG) have been performed along with the S-IgG. The S-IgG correlated well with the neutralizing activity detected by the authentic virus neutralization assay (0.8904. of Spearman’s rho value, p < 0.0001) and sVNT (0.9206. of Spearman’s rho value, p < 0.0001). However, 4 samples (2.3%) of S-IgG and 8 samples (4.5%) of sVNT were inconsistent with negative results for neutralizing activity of the authentic virus neutralization assay. The kinetics of the SARS-CoV-2 neutralizing antibodies and anti-S IgG in severe cases were faster than the mild cases. All the HCWs elicited anti-S IgG titer after the second vaccination. However, the HCWs with history of COVID-19 or positive N-IgG elicited higher anti-S IgG titers than those who did not have it previously. Furthermore, it is difficult to predict the risk of breakthrough infection from anti-S IgG or sVNT antibody titers in HCWs after the second vaccination. Our data shows that the use of anti-S IgG titers as direct quantitative markers of neutralizing capacity is limited. Thus, antibody tests should be carefully interpreted when used as serological markers for diagnosis, treatment, and prophylaxis of COVID-19.

by Madison Hooper, Morgan Reinhart, Stacie B. Dusetzina, Colin Walsh, Kevin N. Griffith Importance The COVID-19 pandemic represents a unique stressor in Americans’ daily lives and access to health services. However, it remains unclear how the pandemic impacted perceived health status and engagement in health-related behaviors. Objective To assess changes in self-reported health outcomes during the COVID-19 pandemic, and to explore trends in health-related behaviors that may underlie the observed health changes. Design Interrupted time series stratified by age, gender, race/ethnicity, educational attainment, household income, and employment status. Setting United States. Participants All adult respondents to the 2016–2020 Behavioral Risk Factor Surveillance System (N = 2,146,384). Exposure Survey completion following the U.S. public health emergency declaration (March-December 2020). January 2019 to February 2020 served as our reference period. Main outcomes and measures Self-reported health outcomes included the number of days per month that respondents spent in poor mental health, physical health, or when poor health prevented their usual activities of daily living. Self-reported health behaviors included the number of hours slept per day, number of days in the past month where alcohol was consumed, participation in any exercise, and current smoking status. Results The national rate of days spent in poor physical health decreased overall (-1.00 days, 95% CI: -1.10 to -0.90) and for all analyzed subgroups. The rate of poor mental health days or days when poor health prevented usual activities did not change overall but exhibited substantial heterogeneity by subgroup. We also observed overall increases in mean sleep hours per day (+0.09, 95% CI 0.05 to 0.13), the percentage of adults who report any exercise activity (+3.28%, 95% CI 2.48 to 4.09), increased alcohol consumption days (0.27, 95% CI 0.18 to 0.37), and decreased smoking prevalence (-1.11%, 95% CI -1.39 to -0.83). Conclusions and relevance The COVID-19 pandemic had deleterious but heterogeneous effects on mental health, days when poor health prevented usual activities, and alcohol consumption. In contrast, the pandemic’s onset was associated with improvements in physical health, mean hours of sleep per day, exercise participation, and smoking status. These findings highlight the need for targeted outreach and interventions to improve mental health in individuals who may be disproportionately affected by the pandemic. …

by Christina M. Kaul, Brandi E. Moore, Emma Kaplan-Lewis, Eunice Casey, Robert A. Pitts, Patricia Pagan Pirallo, Sahnah Lim, Farzana Kapadia, Gabriel M. Cohen, Maria Khan, Ofole Mgbako Background Long-acting injectable HIV pre-exposure prophylaxis (LAI-PrEP) was approved by the U.S. Food and Drug Administration in December 2021. This initial phase of implementation represents a prime opportunity to ensure equitable LAI-PrEP provision to communities often underrepresented in PrEP care before disparities in access and uptake emerge. Herein, we describe the EquiPrEP Project which utilizes an equity-oriented implementation science framework to optimize LAI-PrEP rollout in an urban safety-net clinic in New York City. Methods The primary objectives of this project are to: (1) increase LAI-PrEP initiation overall; (2) increase uptake among groups disproportionately impacted by the HIV epidemic; (3) preserve high PrEP retention while expanding use; and (4) identify barriers and facilitators to LAI-PrEP use. EquiPrEP will enroll 210 PrEP-eligible participants into LAI-PrEP care with planned follow-up for one year. We will recruit from the following priority populations: Black and/or Latine men who have sex with men, Black and/or Latine cisgender women, and transgender women and nonbinary individuals. To evaluate implementation of LAI-PrEP, we will utilize equity-focused iterations of the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework and the Consolidated Framework for Implementation Research (CFIR), in addition to longitudinal surveys and qualitative interviews. Discussion Novel LAI-PrEP formulations carry tremendous potential to revolutionize the field of HIV prevention. Implementation strategies rooted in equity are needed to ensure that marginalized populations have access to LAI-PrEP and to address the structural factors that hinder initiation and retention in care. …

by Qian Feng, Hongcheng Lu, Linquan Wu Background Hepatocellular carcinoma is one of the most common malignancies worldwide, representing a big health-care challenge globally. M2-like macrophages are significantly correlated with tumor progression, metastasis and treatment resistance. Methods Integrative 10 machine learning algorithms were performed to developed a M2-like macrophage related prognostic signature (MRPS). Single-cell RNA-sequencing analysis was performed to dissect the ecosystem of HCC. Several approaches, including TIDE score, immunophenoscore, TMB score and tumor escape score were used to evaluate the predictive role of MRPS in immunology response. Results The optimal MRPS constructed by the combination of stepCox + superPC algorithm served as an independent risk factor and showed stable and powerful performances in predicting the overall survival rate of HCC patients with 2-, 3-, and 4-year AUCs of 0. 763, 0.751, and 0.699 in TCGA cohort. HCC patients with low risk score possessed a more interaction of immunoactivated cells, including NK, CD8+ cytotoxic T, and activated B, and a less interaction of immunosuppressive cells, including Treg, CD4+ exhauster T, and M2-like macrophage. Low risk score indicated a higher PD1&CTLA4 immunophenoscore, higher TMB score, lower TIDE score and lower tumor escape score in HCC, suggesting a better immunotherapy response. The IC50 value of docetaxel, gemcitabine, crizotinib and Osimertinib in HCC with high risk score were lower versus that with low risk score. HCC patients with high risk score had a higher score of cancer-related hallmarks, including angiogenesis, DNA repair, EMT, glycolysis, and NOTCH signaling. Conclusion Our study proposed a novel MRPS for predicting the prognosis, ecosystem and immunotherapy response in HCC. …

by Joseph D. Madison, Brandon C. LaBumbard, Douglas C. Woodhams The use of museum specimens for research in microbial evolutionary ecology remains an under-utilized investigative dimension with important potential. Despite this potential, there remain barriers in methodology and analysis to the wide-spread adoption of museum specimens for such studies. Here, we hypothesized that there would be significant differences in taxonomic prediction and related diversity among sample type (museum or fresh) and sequencing strategy (medium-depth shotgun metagenomic or 16S rRNA gene). We found dramatically higher predicted diversity from shotgun metagenomics when compared to 16S rRNA gene sequencing in museum and fresh samples, with this differential being larger in museum specimens. Broadly confirming these hypotheses, the highest diversity found in fresh samples was with shotgun sequencing using the Rep200 reference inclusive of viruses and microeukaryotes, followed by the WoL reference database. In museum-specimens, community diversity metrics also differed significantly between sequencing strategies, with the alpha-diversity ACE differential being significantly greater than the same comparisons made for fresh specimens. Beta diversity results were more variable, with significance dependent on reference databases used. Taken together, these findings demonstrate important differences in diversity results and prompt important considerations for future experiments and downstream analyses aiming to incorporate microbiome datasets from museum specimens.

by Ayako Aoki, Yu Hara, Hiroaki Fujii, Kota Murohashi, Ryo Nagasawa, Yoichi Tagami, Tatsuji Enomoto, Yutaka Matsumoto, Makoto Masuda, Keisuke Watanabe, Nobuyuki Horita, Nobuaki Kobayashi, Makoto Kudo, Takashi Ogura, Takeshi Kaneko Background Among patients with idiopathic pulmonary fibrosis (IPF), few studies have investigated the clinical impact of anti-fibrotic treatment (AFT) with and without comorbidities. The aim of the study was to determine whether Charlson Comorbidity Index score (CCIS) can predict the efficacy of AFT in patients with IPF. Methods We retrospectively assessed data extracted from the medical records of IPF patients who received anti-fibrotic agents between 2009 and 2019. The collected data included age, sex, CCIS, pulmonary function test, high-resolution computed tomography (HRCT) pattern, gender/age/physiology (GAP) score, and 3-year IPF-related events defined as the first acute exacerbation or death within 3 years after starting AFT. Results We assessed 130 patients (median age, 74 years) who received nintedanib (n = 70) or pirfenidone (n = 60). Median duration of AFT was 425 days. Patients were categorized into high (≥ 3 points) and low (≤ 2 points) CCIS groups. There was no significant difference between the groups in terms of age, sex, duration of AFT, GAP score, or incidence of usual interstitial pneumonia pattern on HRCT except percentage predicted diffusion capacity of lung for carbon monoxide. Also, significant difference was not seen between the groups for 3-year IPF-related events (P = 0.75). Especially, in the low CCIS group but not the high CCIS group, the longer duration of AFT had better disease outcome. Conclusion In the present study, we could not show any relation between CCIS and IPF disease outcomes in patients undergoing AFT, though the longer duration of AFT might be beneficial for IPF outcomes among patients with low CCIS. …

by Pablo Serrano-Lorenzo, Dino Gobelli, Rocío Garrido-Moraga, María J. Esteban-Amo, José R. López-López, Antonio Orduña, Miguel A. de la Fuente, Miguel A. Martín, María Simarro Increasing evidence demonstrate that the electron transfer chain plays a critical role in controlling the effector functions of macrophages. In this work, we have generated a Ndufs4−/− murine macrophage cell lines. The Ndufs4 gene, which encodes a supernumerary subunit of complex I, is a mutational hotspot in Leigh syndrome patients. Ndufs4−/− macrophages showed decreased complex I activity, altered complex I assembly, and lower levels of maximal respiration and ATP production. These mitochondrial respiration alterations were associated with a shift towards a pro-inflammatory cytokine profile after lipopolysaccharide challenge and improved ability to phagocytose Gram-negative bacteria.

Abstract After a period of unprecedented progress against malaria in the 2000s, halving the global disease burden by 2015, gains overall in sub-Saharan Africa have slowed and even reversed in some places, beginning well before the COVID-19 pandemic. The highly effective drugs, treated nets, and diagnostics that fueled the initial progress all face some threats to their effectiveness, and global funding to maintain and increase their use over the long term is not guaranteed. Malaria vaccines are among the most promising new interventions that could accelerate the elimination of malaria. Vaccines are still in early stages of rollout in children, the age group (along with pregnant women) that has been the focus of malaria strategies for a century. At the same time, over the past decade, a case has been made, based largely on evidence from verbal autopsies in at least a few high-transmission areas, that the malaria death rate among adults has been greatly underestimated. Could vaccinating adults help to bring down the adult malaria mortality rate, contribute to reduced transmission, or both? A randomized trial of a malaria vaccine is proposed in Sierra Leone, a highly endemic setting, to shed light on this proposition. …

Infection and Immunity, Ahead of Print.

Infection and Immunity, Ahead of Print.

Infection and Immunity, Ahead of Print.

Infection and Immunity, Ahead of Print.

Infection and Immunity, Ahead of Print.

Abstract Background Several studies suggested pancreatic stone protein (PSP) as a promising biomarker to predict mortality among patients with severe infection. The objective of the study was to evaluate the performance of PSP in predicting intensive care unit (ICU) mortality and infection severity among critically ill adults admitted to the hospital for infection. Methods A systematic search across Cochrane Central Register of Controlled Trials and MEDLINE databases (1966 to February 2022) for studies on PSP published in English using ‘pancreatic stone protein’, ‘PSP’, ‘regenerative protein’, ‘lithostatin’ combined with ‘infection’ and ‘sepsis’ found 46 records. The search was restricted to the five trials that measured PSP using the enzyme-linked immunosorbent assay technique (ELISA). We used Bayesian hierarchical regression models for pooled estimates and to predict mortality or disease severity using PSP, C-Reactive Protein (CRP) and procalcitonin (PCT) as main predictor. We used statistical discriminative measures, such as the area under the receiver operating characteristic curve (AUC) and classification plots. Results Among the 678 patients included, the pooled ICU mortality was 17.8% (95% prediction interval 4.1% to 54.6%) with a between-study heterogeneity (I-squared 87%). PSP was strongly associated with ICU mortality (OR = 2.7, 95% credible interval (CrI) [1.3–6.0] per one standard deviation increase; age, gender and sepsis severity adjusted OR = 1.5, 95% CrI [0.98–2.8]). The AUC was 0.69 for PSP 95% confidence interval (CI) [0.64–0.74], 0.61 [0.56–0.66] for PCT and 0.52 [0.47–0.57] for CRP. The sensitivity was 0.96, 0.52, 0.30 for risk thresholds 0.1, 0.2 and 0.3; respective false positive rate values were 0.84, 0.25, 0.10. Conclusions We found that PSP showed a very good discriminative ability for both investigated study endpoints ICU mortality and infection severity; better in comparison to CRP, similar to PCT. Combinations of biomarkers did not improve their predictive ability. …

Abstract Introduction The aim of this study was to investigate how long hospitalized patients stayed positive to the nasopharyngeal swab, and what demographic and clinical factors influence the time-to-negative swab. Methods We enrolled in a multicenter, observational, retrospective study involving 17 COVID-19 units in eight cities of the Campania, southern Italy all patients hospitalized from March 2020 to May 2021 diagnosed with Severe Acute Respiratory Distress Syndrome-Coronavirus-2 (SARS-CoV-2) infection for whom time-to-negative swab was available. Results 963 patients were enrolled. We defined three groups considering time-to-negative swab: the first including patients with time-to-negative swab before the 26th day, the second including patients with time-to-negative swab from day 26 to day 39, and the third including patients with time-to-negative swab > 39 days. 721 (74.9%) patients belonged to the first group, 194 (20.1%) to the second, and 52 (5.4%) belonged to the third group. Belonging to group 2 and 3 seemed to be influenced by age (p value 

Abstract Introduction Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections commonly cause hospital-acquired infections. The study aimed to compare the outcomes of CRKP infections between patients receiving ceftazidime avibactam +/− aztreonam and polymyxins in a hospital setting with a high prevalence of New Delhi Metallo Beta Lactamase production. Methods We conducted a retrospective cohort study from January 2020 to September 2022 in critically ill adult patients admitted to a non-COVID-19 medical intensive care unit with CRKP infection. The patients were followed up for a total of 30 days or death, whichever was later. Results Of a total of 106 patients included in the study, 65 patients received polymyxins and 41 patients received ceftazidime–avibactam +/− aztreonam. Higher 30-day mortality was noted in the polymyxin group (56.9% vs. 29.2%, P = 0.005). The mean time to event (mortality) in ceftazidime–avibactam +/− aztreonam was 23.9 + 1.5 days which was significantly higher compared to polymyxins (17.9 + 1.2 days, p = 0.006). On Cox regression analysis, after adjusting for the covariates, the hazard ratio for time to event with the use of polymyxin was 2.02 (95% CI: 1.03–3.9). Conclusion Ceftazidime–avibactam + aztreonam is possibly associated with better clinical outcomes in patients infected with CRKP. …

Abstract Purpose Timely and accurate data on the epidemiology of sepsis are essential to inform policy decisions and research priorities. We aimed to investigate the validity of inpatient administrative health data (IAHD) for surveillance and quality assurance of sepsis care. Methods We conducted a retrospective validation study in a disproportional stratified random sample of 10,334 inpatient cases of age ≥ 15 years treated in 2015–2017 in ten German hospitals. The accuracy of coding of sepsis and risk factors for mortality in IAHD was assessed compared to reference standard diagnoses obtained by a chart review. Hospital-level risk-adjusted mortality of sepsis as calculated from IAHD information was compared to mortality calculated from chart review information. Results ICD-coding of sepsis in IAHD showed high positive predictive value (76.9–85.7% depending on sepsis definition), but low sensitivity (26.8–38%), which led to an underestimation of sepsis incidence (1.4% vs. 3.3% for severe sepsis-1). Not naming sepsis in the chart was strongly associated with under-coding of sepsis. The frequency of correctly naming sepsis and ICD-coding of sepsis varied strongly between hospitals (range of sensitivity of naming: 29–71.7%, of ICD-diagnosis: 10.7–58.5%). Risk-adjusted mortality of sepsis per hospital calculated from coding in IAHD showed no substantial correlation to reference standard risk-adjusted mortality (r = 0.09). Conclusion Due to the under-coding of sepsis in IAHD, previous epidemiological studies underestimated the burden of sepsis in Germany. There is a large variability between hospitals in accuracy of diagnosing and coding of sepsis. Therefore, IAHD alone is not suited to assess quality of sepsis care. …

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Abstract Background Despite the fact that prison inmates are a population at higher risk than other groups of suffering from intestinal parasite infections in relation to their living conditions, information about these diseases in prison environments is still scarce. Herein, we analyze the status of intestinal parasite infections in a Spanish prison. Methods A cross-sectional study involving 528 inmates was conducted from April to June 2022 among inmates at Centro Penitenciario Picassent (Valencia, Spain). Stool specimens were examined using the direct wet mount technique, the formol-ether concentration technique, and the Ziehl-Neelsen staining method. We used STATA 16.1 for data analysis. We consider a p-value less than 0.05 significant at a 95% confidence level. Results Of the 528 inmates (471 men and 57 women; a mean age of 41.94 years) enrolled in the study, 83 (15.7%) were infected. Only six species of protozoa were detected. The gut potential microeukaryotic pathobiont Blastocystis sp. was the predominant parasite, accounting for 37 (44.6%) of the infections. Gut parasite amebas (6.6%) and pathobionts (5.3%) were more prevalent than flagellates (2.3%). The prevalence of infection with pathogenic species (8.9%) was similar to that of non-pathogenic species (8.7%). Infection among men (15.2%) was higher than in women (0.6%) (p 

Abstract Background Dialister pneumosintes is an anaerobic, Gram negative bacillus, found in the human oral cavity and associated with periodontitis. It has also been isolated from gastric mucosa and stool samples. Recent case reports implicate D. pneumosintes in local infection such as dental root canals, sinusitis, Lemierres syndrome and brain abscesses, as well as distal infections of the liver and lung through haematogenous spread. Case presentation We present a novel case of aortic graft infection and aortoenteric fistula (AEF) in a 75 year old Caucasian male, associated with D. pneumosintes bacteraemia. Microbiological evaluation of septic emboli in the lower limbs revealed other gastrointestinal flora. This suggests either AEF leading to graft infection and subsequent distal emboli and bacteraemia, or a dental origin of infection which seeded to the graft, resulting in AEF and systemic infection. To our knowledge this is the first report of D. pneumosintes associated aortic graft infection. The patient underwent surgical explantation, oversew of the aorta and placement of extra-anatomical bypass graft in conjunction with antimicrobial therapy, making a good recovery with discharge home after a 35-day hospital admission. Conclusion We report a case of Dialister pneumosintes bacteraemia associated with aortic graft infection. To our knowledge, vascular graft-associated infection with D. pneumosintes has not been reported before. …

Abstract The objective of the study was to analyze the spatial distribution of vaccination coverage of bacterial meningitis vaccine: A, C, W and Y (menacwy) and identify the association between socioeconomic and social environment factors with menacwy vaccine coverage among adolescents in the state of Minas Gerais (MG), Brazil. This is an ecological, mixed study, conducted with secondary data from the 853 municipalities of the State of MG, Brazil, from 2020 to 2022, provided by the information system of the National Immunization Program. For spatial statistical analysis, spatial dependence and the presence of spatial clusters formed by municipalities with high and low vaccination coverage of Menacwy were evaluated. In the year 2021, MG presented the largest vaccination coverage (60.58%) since the introduction of the Menacwy vaccine by the PNI. Regarding the analysis of global regressions, it is observed that for the year 2020, as the MG Index of Social Responsibility-Health increased and MG Index of Social Responsibility—Public Security increased, increased the vaccination coverage of the municipalities of the Menacwy vaccine. Finally, compared to 2021, similar association was observed in relation to the proportion of the population served by the Family Health Strategy of the municipalities of the state of MG and per capita spending on education activities: as this indicator increased, with increased coverage of the Vaccine of the Menacwy vaccine of the state municipalities. They reinforce the importance of assessing the quality-of-care management and health surveillance system, professional training, and damage reduction to populations, especially adolescents. …

Abstract Background The gastrointestinal tract contains a massive microbiota, and targeting the gut could be a potential intervention for sepsis. However, the interaction between sepsis and the intestinal microbiota is defined as an “incompletely understood bidirectional relationship”. Methods This retrospective observational cohort study investigated the fecal microbiota of sepsis patients admitted to the Department of Critical Care Medicine of the Central Hospital of Wuhan, China, from May 2019 to January 2020. 14 septic patients were divided into the non-severe group and the severe group according to the Acute Physiology and Chronic Health Evaluation II (APACHE II) score. Herein, fecal samples were serially collected on admission, the third, fourth, and fifth days, and ICU discharge. The fecal microbiota was analyzed by 16S rRNA gene sequencing and its correlation with clinical parameters was evaluated. Results Bacteroidetes, Firmicutes, and Proteobacteria were dominant phyla at ICU admission, and fecal biodiversity was not significantly different between the non-severe group (APACHE II  15). However, the diversity of the gut microbiota was significantly lower at ICU discharge than that at ICU admission with the extension of treatment time. Further significant difference flora analysis (LEfSe) showed that the genera Veillonella and Ruminococcus were the most discriminant biomarkers at ICU admission in non-severe and severe patients, respectively, while Enterococcus was the most discriminant biomarker at ICU discharge in all septic patients. Of note, liver function tests, including ALT, AST, TBIL, and DBIL correlated with the prevalence of various bacterial genera. Conclusions The diversity of the gut microbiota in patients with sepsis decreases dramatically during ICU stay, and there are distinct dynamic changes in gut microbiota among patients with different severity in sepsis. …

Abstract Background Tuberculosis, along with HIV, is the leading cause of mortality and morbidity globally. Despite the fact that several primary studies have been conducted on the incidence rate of tuberculosis in HIV-infected people in Sub-Saharan Africa, the regional-level tuberculosis incidence rate remains unknown. The objective of this study is to determine the tuberculosis incidence rate and its associated factors in HIV-infected people in Sub-Saharan Africa. Methods A systematic review and meta-analysis were conducted by searching four databases for studies published in English between January 1, 2000, and November 25, 2022. The study was carried out using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method. To assess the quality of the studies, the Joanna Briggs Institute critical appraisal checklist was used. A random-effects model meta-analysis was used to determine the pooled incidence of tuberculosis using STATA version 15. The I2 heterogeneity test was used to assess heterogeneity. Subgroup and sensitivity analyses were performed. Funnel plots and Egger’s regression tests were used to investigate publication bias. The pooled estimate predictors of tuberculosis incidence rate with a 95% confidence interval were also determined using the hazard ratio of each factor (HR). Results Out of a total of 3339 studies, 43 were included in the analysis. The overall pooled incidence rate of tuberculosis in HIV-infected people was 3.49 per 100 person-years (95% CI: 2.88–4.17). In the subgroup analysis, the pooled incidence rate of tuberculosis in HIV-infected children was 3.42 per 100 person-years (95% CI: 1.78, 5.57), and it was 3.79 per 100 person-years (95% CI: 2.63, 5.15) in adults. A meta-analysis revealed that underweight (AHR = 1.79, 95% CI: 1.61–1.96), low CD4 count (AHR = 1.23, 95% CI: 1.13–1.35), male gender (AHR = 1.43, 95% CI: 1.22–1.64), advanced WHO clinical stages (AHR = 2.29, 95% CI: 1.34–3.23), anemia (AHR = 1.73, 95% CI: 1.34–2.13), bedridden or ambulatory (AHR = 1.87, 95%), lack of isoniazid preventive therapy (AHR = 3.32, 95% CI: 1.08–2.28), and lack of cotrimoxazole (AHR = 1.68, 95% CI: 1.08–2.28) were risk factors for tuberculosis incidence. HIV patients who received antiretroviral therapy had a 0.53 times higher risk of acquiring tuberculosis than HIV patients who did not receive antiretroviral therapy (AHR = 0.53; 95% CI: 0.3–0.77). Conclusion In this systematic review and meta-analysis study, the incidence rate of tuberculosis among HIV-positive people was higher than the WHO 2022 Africa regional estimated report. To reduce the incidence of tuberculosis among HIV patients, HIV patients should take isoniazid prevention therapy (IPT), cotrimoxazole prophylaxis, and antiretroviral therapy (ART) without interruption, as well as increase the frequency and diversity of their nutritional intake. Active tuberculosis screening should be increased among HIV-infected people. …

Journal of Medical Virology, Volume 95, Issue 9, September 2023.

Journal of Medical Virology, Volume 95, Issue 9, September 2023.

Journal of Medical Virology, Volume 95, Issue 9, September 2023.

Journal of Medical Virology, Volume 95, Issue 9, September 2023.

Journal of Medical Virology, Volume 95, Issue 9, September 2023.

Journal of Medical Virology, Volume 95, Issue 9, September 2023.

Journal of Medical Virology, Volume 95, Issue 9, September 2023.

AbstractEbola virus disease is marked by the rapid virus replication and spread. Ebola virus (EBOV) enters the cell by macropinocytosis, replicates in the cytoplasm, and nascent virions egress from the cell surface to infect neighboring cells. Here, we show that EBOV uses an alternate route to disseminate: tunneling nanotubes (TNTs). TNTs, an actin-based long-range intercellular communication system, allows for direct exchange of cytosolic constituents between cells. Using live, scanning electron and high-resolution quantitative 3D-microscopy, we show that EBOV infection of primary human cells results in the enhanced formation of TNTs, containing viral nucleocapsids. TNTs promoted the intercellular transfer of nucleocapsids in the absence of live virus, and virus could replicate in cells devoid of entry factors after initial stall. Our studies suggest an alternate model of EBOV dissemination within its host, laying the groundwork for further investigations into the pathogenesis of filoviruses and, importantly, stimulating new areas of antiviral design.

AbstractTo gain insight into interactions among respiratory viruses, we modeled influenza A virus (IAV) - SARS-CoV-2 coinfections using differentiated human airway epithelial cultures. Replicating IAV induced a more robust interferon response than SARS-CoV-2 and suppressed SARS-CoV-2 replication in both sequential and simultaneous infections, whereas SARS-CoV-2 did not enhance host cell defense during influenza infection or suppress IAV replication. Oseltamivir, an antiviral targeting influenza, reduced IAV replication during coinfection but also reduced the host antiviral response and restored SARS-CoV-2 replication. These results demonstrate how perturbations in one viral infection can impact its effect on a coinfecting virus.

AbstractBacterial vaginosis (BV) is a dysbiotic condition of the vaginal microbiome associated with higher risk of infection by Neisseria gonorrhoeae - the cause of gonorrhea. Here we test if one known facet of BV - the presence of bacterial cytolysins – leads to mobilization of intracellular contents that enhance gonococcal virulence. We cloned and expressed recombinant vaginolysin (VLY), a cytolysin produced by the BV-associated bacterium Gardnerella, verifying that it liberates contents of cervical epithelial (HeLa) cells, while vector control preparations did not. We tested if VLY mediates a well-known gonococcal virulence mechanism – the molecular mimicry of host glycans. To evade host immunity, N. gonorrhoeae caps its lipooligosaccharide (LOS) with α2-3-linked sialic acid. For this, gonococci must scavenge a metabolite made inside host cells. Flow-cytometry based lectin-binding assays showed that gonococci exposed to vaginolysin-liberated contents of HeLa cells displayed greater sialic acid capping of their LOS. This higher level of bacterial sialylation was accompanied by increased binding of the complement regulatory protein Factor H, and greater resistance to complement attack. Together these results suggest that cytolytic activities present during BV may enhance the ability of N. gonorrhoeae to capture intracellular metabolites and evade host immunity via glycan molecular mimicry.

IntroductionOlder surgical candidates are at increased risk of a phenomenon known as postoperative cognitive dysfunction (POCD). Several studies have looked at the incidence of POCD at different time points following surgery, using different study methods. Fewer have assessed whether changes in cognition after surgery are attributable to surgery and how they impact patient function and quality of life. The aim of this systematic review is to summarise and appraise studies addressing any of the following research questions (RQs): (RQ1) what is the frequency of POCD after non-cardiac surgery?; (RQ2) is non-cardiac surgery associated with an increased risk of cognitive decline?; (RQ3) is POCD after non-cardiac surgery associated with patient-important outcomes? Methods and analysisThis protocol adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. Three electronic databases (MEDLINE, PsycINFO and EMBASE) will be systematically searched from their inception date. Identified studies will be screened by two reviewers for eligibility using Covidence, and data will be extracted into a standardised electronic form. We will evaluate methodological quality of included studies using the Quality In Prognosis Studies and its adaptation to the overall prognosis question, and the CLARITY risk of bias for cohort and case–control studies. For RQ1, we will estimate an average POCD frequency at different time points by performing a meta-analysis of included studies when appropriate. For RQ2 and RQ3, we will extract and meta-analyse the effect measures for the association of surgery with cognitive decline when compared with the non-surgical comparator, and association of cognitive changes with functional changes, quality of life and other patient-important outcomes based on available evidence. We will narratively summarise and discuss the different methods implemented in the existing studies to answer the three RQs, and when meta-analysis is deemed infeasible, we will qualitatively report the results of the included studies. Ethics and disseminationThis project involves the collection and analysis of data from previously published studies and therefore does not require ethics approval. We plan to present the findings of this research project at peer-reviewed conferences and publish the results in peer-reviewed journals. PROSPERO registration numberCRD42022370674. …

ObjectiveThis survey investigated the relationship between social isolation, depression, nutritional status and quality of life among community-dwelling older adults during COVID-19. DesignThis was a cross-sectional survey study. SettingCommunities in Pudong New Area, Shanghai, China that have contracted with Renji Hospital, affiliated with Shanghai Jiao Tong University School of Medicine. ParticipantsFrom May to July 2022, 406 community-dwelling older adults were selected by convenience sampling in Shanghai, China. Primary and secondary outcome measuresThe Lubben Social Network Scale, Geriatric Depression Scale, 36-item Short Form Health Survey Scale and risk assessment of malnutrition were used in older adults. Mediation models were constructed to determine the mediating role of depression and nutritional status on social isolation and quality of life among older adults. ResultsThe prevalence of social isolation among older adults in the community was 44.3%. The total social isolation score in community-dwelling older adults was positively associated with the total malnutrition risk and quality of life scores, and negatively associated with depression (p

ObjectivesTargeted testing policy for HIV/syphilis at Dutch sexual health centres (SHCs) was evaluated for its efficiency in younger heterosexuals but not for heterosexuals ≥25 years. Currently, all older heterosexuals are tested for HIV/syphilis at SHCs. To explore possibilities for increased efficiency of testing in heterosexuals aged >25 years, this study aimed to identify determinants of HIV and syphilis diagnoses that could be used in targeted testing strategies. DesignAn observational study using surveillance data from all Dutch SHC. ParticipantsWomen and heterosexual men aged >25 years visiting SHC between 2015 and 2021. Primary and secondary outcome measuresThe primary outcome was HIV/syphilis diagnosis, determinants of a diagnosis were analysed. Based on these determinants and their applicability in SHC practice, different targeted testing scenarios were evaluated. For each scenario, the percentage of consultations involving HIV and syphilis testing and the total amount of missed HIV and syphilis diagnoses were calculated. Results109 122 consultations were included among 75 718 individuals. The strongest determinants of HIV/syphilis diagnosis were HIV/syphilis-specific symptoms (adjusted OR (aOR) 34.9 (24.1–50.2)) and receiving partner notification (aOR 18.3 (13.2–25.2)), followed by low/middle education level (aOR 2.8 (2.0–4.0)), male sex (aOR 2.2 (1.6–3.0)) and age ≥30 years (aOR 1.8 (1.3–2.5)). When applying feasible determinants to targeted testing scenarios, HIV/syphilis testing would have been conducted in 54.5% of all consultations, missing 2 HIV and 3 syphilis diagnoses annually (13.4% and 11.4% of all diagnoses, respectively). In the scenario with the lowest number of missed HIV/syphilis diagnoses (0.3 HIV and 2 syphilis diagnoses annually), HIV/syphilis testing would have been conducted in 74.2% of all consultations. ConclusionsIn any targeted testing scenario studied, HIV and/or syphilis diagnoses would have been missed. This raises the question whether it is acceptable to put any of these scenarios into practice. This study contributes to a discussion about the impact of targeted testing policy. …

IntroductionCoronary heart disease (CHD) is one of the common cardiovascular diseases that seriously jeopardise human health, and endothelial inflammation and dyslipidaemia are the initiating links leading to its occurrence. Percutaneous coronary intervention (PCI) is one of the most effective surgical treatments for CHD with narrowed or blocked blood vessels, which can quickly unblock the blocked vessels and restore coronary blood supply. However, most patients may experience coronary microcirculation disorders (CMDs) and decreased cardiac function after PCI treatment, which directly affects the efficacy of PCI and the prognosis of patients. Preprotein converting enzyme subtilisin/Kexin 9 (PCSK9) inhibitors are novel pleiotropy lipid-lowering drug with dual anti-inflammation and lipid-lowering effects, and represent a new clinical pathway for rapid correction of dyslipidaemia. Therefore, we designed this protocol to systematically evaluate the effects of PCSK9 inhibitors on coronary microcirculation and cardiac function in patients with CHD after PCI, and to provide high-quality evidence-based evidence for the clinical application of PCSK9 inhibitors. Methods and analysisThis protocol is reported strictly in accordance with the 2020 Preferred Reporting Items for Systematic Reviews and Meta-analyses Protocols Guidelines. We will search PubMed, EMBASE, Web of Science and three Chinese databases (CNKI, Wanfang and VIP database) according to preset search strategies, without language and publication data restrictions. We will work with manual retrieval to screen references that have been included in the literature. Google Scholar will be used to search for grey literature. The final included literature must meet the established inclusion criteria. Titles, abstracts and full text will be extracted independently by two reviewers, and disagreements will be resolved through discussion or the involvement of a third reviewer. Extracted data will be analysed using Review Manager V.5.3. The Cochrane Risk of Bias Tool will be used to evaluate the risk of bias. Publication bias will be assessed by funnel plots. Heterogeneity will be assessed by I2 test and subgroup analyses will be used to further investigate potential sources of heterogeneity. The quality of the literature will be assessed by GRADE score. This protocol will start in January 2026 and end in December 2030. Ethics and disseminationThis study is a systematic review of published literature data and no special ethical approval was required. PROSPERO registration numberCRD42022346189. …

IntroductionPrompt detection of hepatocellular carcinoma (HCC) in patients with chronic liver diseases is critical for enhancing prognosis. Existing imaging techniques and serum markers fall short of clinical needs. This study aims to establish a non-invasive diagnostic model for early HCC detection in the Chinese population. Methods and analysisThis prospective, multicentre, observational study will enrol 2000 participants, including HCC patients, those with chronic liver diseases (hepatitis, cirrhosis and benign liver space-occupying lesions), and healthy individuals. The study will collect demographic data and blood samples, which will be used to test α-fetoprotein (AFP), des--carboxy-prothrombin (DCP) and circulating tumour DNA (ctDNA) methylation. The GAMAD (Gender+Age+Methylation+AFP+DCP) model involving gender, age, ctDNA methylation signature, AFP and DCP will be developed and blindly validated in training and validation sets (1400 and 600 cases, respectively). Primary endpoints include sensitivity, specificity and accuracy (receiver operating characteristic curves; area under the curve value) of GAMAD for HCC and/or high-risk HCC groups. Secondary endpoints involve comparing GAMAD with the established GALAD (Gender+Age+AFP-L3+AFP+DCP) model and each blood index (AFP, DCP and methylation signature) to evaluate: (1) GAMAD’s clinical utility for HCC patients in all stages according to different staging systems; (2) GAMAD’s discrimination ability for patients in various subgroups, including liver cirrhosis (LC) related HCC and LC, hepatitis B virus (HBV) related HCC and HBV, hepatitis C virus (HCV) related HCC and HCV, and non-alcoholic fatty liver disease (NAFLD) related HCC and NAFLD. Ethics and disseminationThis trial has been approved by the Medical Ethics Committees of the First Hospital of Jilin University (#22K073-001), the Eastern Hepatobiliary Surgery Hospital, Naval Medical University (#EHBHKY2023-H0003-P001) and Tianjin Third Central Hospital (#IRB2023-007-01). All participants in the trial will provide written informed consent. Results of this study will be disseminated in peer-reviewed scientific journals and at conferences nationally and internationally. Trial registration numberNCT05626985. …

Strategic use of Plasmodium falciparum genetic variation has great potential to inform public health actions for malaria control and elimination. Malaria molecular surveillance (MMS) begins with a strategy to identify and collect parasite samples, guided by public-health priorities. In this review we discuss sampling design practices for MMS and point out epidemiological, biological, and statistical factors that need to be considered. We present examples for different use cases, including detecting emergence and spread of rare variants, establishing transmission sources and inferring in malaria transmission intensity. This review will potentially guide the collection of samples and data, serve as a starting point for further methodological innovation, and enhance utilization of MMS to support malaria elimination.

Tuberculosis (TB) is the leading infectious killer of adults worldwide and responsible for almost 2 million deaths each year. The fact that the disease is entirely preventable and curable makes these statistics especially bleak, and they speak to the gross inequalities that drive TB morbidity and mortality today. While in wealthier countries and populations, TB is considered a “disease of the past”, it was only in the mid-1950s that modern chemotherapeutic approaches to TB were developed. Prior to this time, “rest cures”, isolation in sanitoria, and painful surgeries were the norm, virtually guaranteeing death for most.