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Emily Frey,1 Carrie D Johnston,2 Eugenia L Siegler3 1Department of Medicine, Weill Cornell/New York Presbyterian Hospital, New York, NY, USA; 2Division of Infectious Diseases, Weill Cornell Medicine, New York, NY, USA; 3Division of Geriatrics and Palliative Medicine, Weill Cornell Medicine, New York, NY, USACorrespondence: Emily Frey, Department of Medicine, Weill Cornell Medicine, 505 East 70th Street, New York, NY, 10021, USA, Tel +1 212 746 4749, Fax +1 212 746 4609, Email eef9007@nyp.orgAbstract: With improved access to antiretroviral therapy throughout the world, people are aging with HIV, and a large portion of the global population of people with HIV (PWH) is now age 50 or older. Older PWH experience more comorbidities, aging-related syndromes, mental health challenges, and difficulties accessing fundamental needs than the population of older adults without HIV. As a result, ensuring that older PWH are receiving comprehensive healthcare can often be overwhelming for both PWH and the providers. Although there is a growing literature addressing the needs of this population, gaps remain in care delivery and research. In this paper, we suggest seven key components to any healthcare program designed to address the needs of older people with HIV: management of HIV, comorbidity screening and treatment, primary care coordination and planning, attention to aging related-syndromes, optimization of functional status, support of behavioral health, and improved access to basic needs and services. We review many of the difficulties and controversies related to the implementation of these components, which include the absence of screening guidelines for this population and the challenges of care integration, and we suggest key next steps.Keywords: older people with HIV, care integration, antiretroviral therapy, multimorbidity, aging-related syndromes

Investigates the influence of dental to facial midline discrepancies on dental attractiveness rating. Components of functional occlusion; Treatment of malocclusion; Establishment of buccal inter-digitation; Impact of symmetrical dental arrangement on smile.

This study evaluated the effect of etch time on the shear bond strength obtained when bonding to the buccal enamel of first molar teeth. Recently extracted first molar teeth were etched with 37 per cent phosphoric acid gel for 15, 30 and 60 seconds. Preformed cylinders of Concise composite resin were then bonded to the buccal surfaces of the molar teeth. After storage in water for 24 hours at 37°C, the specimens were debonded in a direction parallel to the buccal surface. Examination of the shear bond strengths showed significant differences in shear bond strength between 15 and 30 seconds (P < 0.01) and between 15 and 60 seconds (P< 0.001). Weibull analysis revealed that the probability of bond survival increased as etch time increased, however, the difference between 30 and 60 seconds was not statistically significant. The results indicate that, despite current recommendations of a 15-second etch for premolars, canines and anterior teeth, an etching time of at least 30 seconds should be used when bonding to the buccal surfaces of first molars. A further increase in etching time to 60 seconds produces no significant increase in bond strength. [ABSTRACT FROM AUTHOR]

This study evaluated the effect of sandblasting foil mesh molar tube bases on the shear bond strength obtained when bonding to first molar teeth. Fifty-two recently extracted first molar teeth were etched with 35 per cent phosphoric acid gel for 30 seconds. Twenty-six sandblasted 'A' Company molar tube attachments and 26 non-sandblasted attachments were then bonded to the teeth using Phase II orthodontic bonding resin. After storage in water for 24 hours at 37°C, the specimens were debonded in a direction parallel to the buccal surface. Survival analysis using the Weibull function revealed that for a 90 per cent probability of survival, the predicted bond strengths for sandblasted and non-sandblasted bases were 1.76 and 1.66 MPa, respectively. For larger shear stresses, the probabilities of bond survival with sandblasted molar tubes were greater than with non-sandblasted molar tubes although the differences were small, which may be explained by the large proportion of bond failures which occurred at the resin to enamel interface in both groups. It was concluded that sandblasting foil mesh bases is likely to provide only a minimal improvement in clinical performance when bonding to molar teeth. [ABSTRACT FROM AUTHOR]

Abstract: Pexa, BS, Johnston, CD, Elder, EE, Ford, KR, Patterson, MQ, and Myers, JB. Pool-based surfboard elicits activation of posterior shoulder muscles during a surfing stroke. J Strength Cond Res 38(7): 1300-1304, 2024-Surfboard paddling may activate posterior shoulder muscles, which are critical to baseball pitchers' injury risk and performance. The purpose of this study was to measure posterior shoulder muscle activation during different phases of the surf stroke (propulsion vs. recovery) on a pool-based surfboard. Twenty healthy active adult subjects completed a familiarization and testing session with the pool-based surfboard. During the testing session, electromyography (EMG) sensors were placed on 6 posterior shoulder muscles: latissimus dorsi, infraspinatus, posterior deltoid, upper trapezius, middle trapezius, and lower trapezius. Subjects completed 4 laps in a pool at 3 separate resistances (low, moderate, and heavy) in a randomized order. The peak EMG signal during each phase (propulsion and recovery) was recorded. A 2-way within subject ANOVA (resistance-by-phase) with post hoc Bonferroni's corrections was used to identify differences in EMG activation. There was a significant main effect of phase for the latissimus dorsi (F = 91.3, p < 0.001), upper trapezius (F = 36.5, p < 0.001), middle trapezius (F = 33.8, p < 0.001), and lower trapezius (F = 21.6, p < 0.001). The latissimus dorsi demonstrated higher activation during the propulsion phase (p < 0.001), and all trapezius muscles demonstrated higher activation during the recovery phase (p < 0.001). There was a significant main effect of resistance for the posterior deltoid (F = 3.4, p = 0.043), with higher muscle activation in the low resistance trials compared with the heavy resistance trials (p = 0.036). Recreationally active individuals demonstrate activation of the posterior shoulder when using a pool-based surfboard. This pool-based surfboard may be beneficial to activate the posterior musculature and may be more accessible than standard surfing to baseball athletes., (Copyright © 2024 National Strength and Conditioning Association.)

Purpose: Neuromuscular deficits and atrophy after anterior cruciate ligament reconstruction (ACLR) may be accompanied by changes in muscle composition and poor quadriceps muscle quality (QMQ). Quadriceps atrophy occurs after ACLR but improves within the first three postoperative months, yet this hypertrophy could be attributable to increases in noncontractile tissue (i.e., poor QMQ). The purposes of this study were to evaluate changes in QMQ after ACLR and to determine if changes in QMQ and cross-sectional area (CSA) occur in parallel or independently., Methods: A longitudinal prospective cohort design was implemented to evaluate QMQ and CSA in 20 individuals with ACLR and 12 healthy controls. Participants completed three testing sessions (baseline/presurgery, 1 month, and 3 months) during which ultrasound images were obtained from the vastus lateralis (VL) and rectus femoris (RF). QMQ was calculated as the echo intensity (EI) of each image, with high EI representing poorer QMQ. Anatomical CSA was also obtained from each image., Results: RF and VL EI were greater at 1 and 3 months in the ACLR limb compared with baseline and the contralateral limb and did not change between 1 and 3 months. VL and RF CSA in the ACLR limb were smaller at 1 and 3 months compared with the contralateral limb and controls (VL only) but increased from 1 to 3 months. Changes in QMQ and CSA were not correlated., Conclusions: QMQ declines within the first month after ACLR and does not improve by 3 months although hypertrophy occurs, suggesting that these morphological characteristics change independently after ACLR. Poorer QMQ represents greater concentration of noncontractile tissues within the muscle and potentially contributes to chronic quadriceps dysfunction observed after ACLR., (Copyright © 2023 by the American College of Sports Medicine.)

Background: Quadriceps dysfunction is common following anterior cruciate ligament reconstruction and contributes to aberrant gait biomechanics. Changes in quadriceps composition also occur in these patients including greater concentrations of non-contractile tissue. The purpose of this study was to evaluate associations between quadriceps composition, function, and gait biomechanics in individuals with anterior cruciate ligament reconstruction., Methods: Forty-eight volunteers with anterior cruciate ligament reconstruction completed gait biomechanics and quadriceps function and composition assessments. Gait biomechanics were sampled during downhill walking (-10° slope) on an instrumented treadmill. Quadriceps function (peak torque and rate of torque development) was assessed via maximal isometric contractions, while composition was evaluated via ultrasound echo intensity., Findings: Greater quadriceps peak torque was associated with a greater peak knee extension moment (r = 0.365, p = 0.015). Greater vastus lateralis echo intensity (i.e. poorer muscle quality) was associated with less knee flexion displacement (r = -0.316, p = 0.032). Greater echo intensity of the vastus lateralis (r = -0.298, p = 0.044) and rectus femoris (r = -0.322, p = 0.029) was associated with a more abducted knee angle at heel strike. Quadriceps peak torque explained 11-16% of the variance in echo intensity., Interpretation: Both quadriceps function and composition influence aberrant gait biomechanics following anterior cruciate ligament reconstruction. Quadriceps composition appears to provide insight into quadriceps dysfunction independent of muscle strength, as they associated with different gait biomechanics outcomes and shared minimal variance. Future research is necessary to determine the influence of changes in quadriceps composition on joint health outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Fusobacterium nucleatum (Fn), a bacterium present in the human oral cavity and rarely found in the lower gastrointestinal tract of healthy individuals 1 , is enriched in human colorectal cancer (CRC) tumours 2-5 . High intratumoural Fn loads are associated with recurrence, metastases and poorer patient prognosis 5-8 . Here, to delineate Fn genetic factors facilitating tumour colonization, we generated closed genomes for 135 Fn strains; 80 oral strains from individuals without cancer and 55 unique cancer strains cultured from tumours from 51 patients with CRC. Pangenomic analyses identified 483 CRC-enriched genetic factors. Tumour-isolated strains predominantly belong to Fn subspecies animalis (Fna). However, genomic analyses reveal that Fna, considered a single subspecies, is instead composed of two distinct clades (Fna C1 and Fna C2). Of these, only Fna C2 dominates the CRC tumour niche. Inter-Fna analyses identified 195 Fna C2-associated genetic factors consistent with increased metabolic potential and colonization of the gastrointestinal tract. In support of this, Fna C2-treated mice had an increased number of intestinal adenomas and altered metabolites. Microbiome analysis of human tumour tissue from 116 patients with CRC demonstrated Fna C2 enrichment. Comparison of 62 paired specimens showed that only Fna C2 is tumour enriched compared to normal adjacent tissue. This was further supported by metagenomic analysis of stool samples from 627 patients with CRC and 619 healthy individuals. Collectively, our results identify the Fna clade bifurcation, show that specifically Fna C2 drives the reported Fn enrichment in human CRC and reveal the genetic underpinnings of pathoadaptation of Fna C2 to the CRC niche., (© 2024. The Author(s).)

Accumulating studies have demonstrated the presence of viable and metabolically active bacterial communities within a range of solid tumor types. However, the precise mechanisms by which these microbes modulate their infected tumor niches or impact patient responses to cancer treatments remain to be elucidated. Recently, Colbert et al. revealed that L-lactate produced by intratumoral Lactobacillus iners reprograms metabolic capabilities of cervical tumors to support chemoradiotherapy resistance. This finding has implications for many solid cancer types., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Oral spirochetes are among a small group of keystone pathogens contributing to dysregulation of tissue homeostatic processes that leads to breakdown of the tissue and bone supporting the teeth in periodontal disease. Additionally, our group has recently demonstrated that Treponema are among the dominant microbial genera detected intracellularly in tumor specimens from patients with oral squamous cell carcinoma. While over 60 species and phylotypes of oral Treponema have been detected, T. denticola is one of the few that can be grown in culture and the only one in which genetic manipulation is regularly performed. Thus, T. denticola is a key model organism for studying spirochete metabolic processes, interactions with other microbes, and host cell and tissue responses relevant to oral diseases, as well as venereal and nonvenereal treponematoses whose agents lack workable genetic systems. We previously demonstrated improved transformation efficiency using an Escherichia coli-T. denticola shuttle plasmid and its utility for expression in T. denticola of an exogenous fluorescent protein that is active under anaerobic conditions. Here, we expand on this work by characterizing T. denticola Type I and Type II restriction-modification (R-M) systems and designing a high-efficiency R-M-silent "SyngenicDNA" shuttle plasmid resistant to all T. denticola ATCC 35405 R-M systems. Resequencing of the ATCC 33520 genome revealed an additional Type I R-M system consistent with the relatively low transformation efficiency of the shuttle plasmid in this strain. Using SyngenicDNA approaches, we optimized shuttle plasmid transformation efficiency in T. denticola and used it to complement a defined T. denticola ΔfhbB mutant strain. We further report the first high-efficiency transposon mutagenesis of T. denticola using an R-M-silent, codon-optimized, himarC9 transposase-based plasmid. Thus, use of SyngenicDNA-based strategies and tools can enable further mechanistic examinations of T. denticola physiology and behavior., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Hepatic steatosis, including nonalcoholic fatty liver disease (NAFLD), is common among people with HIV (PWH). We present baseline steatosis prevalence and cardiometabolic characteristics among REPRIEVE substudy participants., Methods: REPRIEVE is an international, primary cardiovascular disease prevention, randomized, controlled trial of pitavastatin calcium vs. placebo among 7769 PWH ages 40-75 years on antiretroviral therapy (ART) and with low-to-moderate cardiovascular risk. A subset of participants underwent noncontrast computed tomography, with hepatic steatosis defined as mean hepatic attenuation less than 40 HU or liver/spleen ratio less than 1.0, and NAFLD defined as steatosis in the absence of frequent alcohol use or viral hepatitis., Results: Of 687 evaluable persons, median age was 51 years, BMI 27 kg/m 2 , CD4 + T-cell count 607 cells/μl; 17% natal female sex, 36% Black, 24% Hispanic, and 98% HIV-1 RNA less than 400 copies/ml. Hepatic steatosis prevalence was 22% (149/687), and NAFLD 21% (96/466). Steatosis/NAFLD prevalence was higher in men and with older age, non-Black race, and higher BMI and waist circumference. Both were associated with BMI greater than 30 kg/m 2 , metabolic syndrome components, higher atherosclerotic cardiovascular disease (ASCVD) risk score, HOMA-IR, LpPLA-2 and hs-CRP, and lower high-density lipoprotein cholesterol. Of HIV-specific/ART-specific characteristics, only history of an AIDS-defining illness was more common among persons with steatosis/NAFLD. After adjusting for age, sex and race/ethnicity, BMI greater than 30 kg/m 2 , HOMA-IR greater than 2.0, Metabolic syndrome and each of its components were associated with NAFLD prevalence., Conclusion: In this cohort with controlled HIV and low-to-moderate cardiovascular risk, hepatic steatosis and NAFLD were common and associated with clinically relevant metabolic and inflammatory disturbances but not current HIV-related or ART-related factors., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Single-cell RNA sequencing (scRNAseq) technologies have been beneficial in revealing and describing cellular heterogeneity within mammalian tissues, including solid tumors. However, many of these techniques apply poly(A) selection of RNA, and thus have primarily focused on determining the gene signatures of eukaryotic cellular components of the tumor microenvironment. Microbiome analysis has revealed the presence of microbial ecosystems, including bacteria and fungi, within human tumor tissues from major cancer types. Imaging data have revealed that intratumoral bacteria may be located within epithelial and immune cell types. However, as bacterial RNA typically lacks a poly(A) tail, standard scRNAseq approaches have limited ability to capture this microbial component of the tumor microenvironment. To overcome this, we describe the invasion-adhesion-directed expression sequencing (INVADEseq) approach, whereby we adapt 10x Genomics 5' scRNAseq protocol by introducing a primer that targets a conserved region of the bacterial 16S ribosomal RNA gene in addition to the standard primer for eukaryotic poly(A) RNA selection. This 'add-on' approach enables the generation of eukaryotic and bacterial DNA libraries at eukaryotic single-cell level resolution, utilizing the 10x barcode to identify single cells with intracellular bacteria. The INVADEseq method takes 30 h to complete, including tissue processing, sequencing and computational analysis. As an output, INVADEseq has shown to be a reliable tool in human cancer cell lines and patient tumor specimens by detecting the proportion of human cells that harbor bacteria and the identities of human cells and intracellular bacteria, along with identifying host transcriptional programs that are modulated on the basis of associated bacteria., (© 2023. Springer Nature Limited.)

27 strains representing eight new Prevotella species were isolated from rumen of a single sheep in eight weeks interval. One of the putative species encompassing the highest number of isolated strains which also exhibited some genetic variability in preliminary data, was then selected for description of a novel species. We examined six strains in genomic and phenotypic detail, two of which may actually be the same strain isolated nearly three weeks apart. Other strains formed clearly diverged intraspecies lineages as evidenced by core genome phylogeny and phenotypic differences. Strains of the proposed new Prevotella species are strictly saccharolytic as is usual for rumen Prevotella, and use plant cell-wall xylans and pectins for growth. However, the range of cell-wall polysaccharides utilised for growth is rather limited compared to rumen generalists such as Prevotella bryantii or Prevotella ruminicola and this extends also to the inability to utilise starch, which is unexpected for the members of the genus Prevotella. Based on the data obtained, we propose Prevotella communis sp. nov. to accommodate strain E1-9 T as well as other strains with the similar properties. The proposed species is widespread: two other strains were previously isolated from sheep in Japan and is also common in metagenomic data of cattle and sheep rumen samples from Scotland and New Zealand. It was also found in a collection of metagenome-assembled genomes originating from cattle in Scotland. Thus, it is a ubiquitous bacterium of domesticated ruminants specialising in degradation of a somewhat restricted set of plant cell wall components., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Context: Individuals who undergo anterior cruciate ligament reconstruction (ACLR) are at higher risk of posttraumatic osteoarthritis. Altered joint tissue loading caused by aberrant gait biomechanics leads to deleterious changes in joint health linked to the onset of posttraumatic osteoarthritis. Knee braces have been used to modify joint tissue loading in individuals with joint injury, yet the effects of walking with a brace after ACLR on biomechanical, biochemical, and structural cartilage outcomes are unknown., Objective: To compare biomechanical, biochemical, and structural outcomes between braced and nonbraced walking in individuals with ACLR., Design: Crossover study., Setting: Research laboratory., Patients or Other Participants: A total of 34 individuals with unilateral ACLR (18 females, 16 males; time since ACLR = 50.1 ± 36.8 months)., Intervention(s): Gait biomechanics were assessed during braced and unbraced conditions on separate days., Main Outcome Measure(s): Vertical ground reaction force, knee-flexion angle, and internal knee-extension moment waveforms were evaluated throughout the stance phase and compared between conditions. Percentage changes in serum cartilage oligomeric matrix protein (%ΔCOMP) and femoral cartilage cross-sectional area (%ΔCSA) measured via ultrasound were calculated after a 3000-step walking protocol., Results: Braced walking increased the knee-flexion angle (largest difference = 3.56°; Cohen d effect size = 1.72) and knee-extension moment (largest difference = -0.48% body weight × height; Cohen d effect size = -1.14) compared with nonbraced walking but did not influence vertical ground reaction force. Whereas no difference (P = .20) in %ΔCOMP existed between the braced and nonbraced conditions in the entire cohort (n = 30 with complete blood data), a larger increase (P = .04) in %ΔCOMP was seen during nonbraced than braced walking in individuals who demonstrated increased COMP during nonbraced walking. No difference (P = .86) in %ΔCSA was present between the braced and nonbraced conditions., Conclusions: Braced walking may improve sagittal-plane gait biomechanics and %ΔCOMP in a subset of individuals who demonstrate a typical increased COMP response to load (ie, increase in COMP) after nonbraced walking., (© by the National Athletic Trainers’ Association, Inc.)

Extracellular vesicles (EVs) are nanoparticles with a role in intercellular communication. Cell-free mitochondrial DNA (cf-mtDNA) has been associated with cognitive dysfunction in people with HIV (PWH). We conducted a nested case-control study to test the hypothesis that plasma EVs are associated with cf-mtDNA and cognitive dysfunction in older PWH. A machine learning-based model identified total EVs, including select EV subpopulations, as well as urine cf-mtDNA and 4-meter walk time carry power to predict the neurocognitive impairment. These features resulted in an AUC-ROC of 0.845 + / - 0.109 (0.615, 1.00)., (© 2023. The Author(s) under exclusive licence to The Journal of NeuroVirology, Inc.)

Chronic gastric infection with Helicobacter pylori can lead to progressive tissue changes that culminate in cancer, but how H. pylori adapts to the changing tissue environment during disease development is not fully understood. In a transgenic mouse gastric metaplasia model, we found that strains from unrelated individuals differed in their ability to infect the stomach, to colonize metaplastic glands, and to alter the expression of the metaplasia-associated protein TFF3. H. pylori isolates from different stages of disease from a single individual had differential ability to colonize healthy and metaplastic gastric glands. Exposure to the metaplastic environment selected for high gastric colonization by one of these strains. Complete genome sequencing revealed a unique alteration in the frequency of a variant allele of the putative adhesin sabB , arising from a recombination event with the related sialic acid binding adhesin (SabA) gene. Mutation of sabB in multiple H. pylori strain backgrounds strongly reduced adherence to both normal and metaplastic gastric tissue, and highly attenuated stomach colonization in mice. Thus, the changing gastric environment during disease development promotes bacterial adhesin gene variation associated with enhanced gastric colonization. IMPORTANCE Chronic infection with Helicobacter pylori is the primary risk factor for developing stomach cancer. As disease progresses H. pylori must adapt to a changing host tissue environment that includes induction of new cell fates in the cells that line the stomach. We tested representative H. pylori isolates collected from the same patient during early and later stages of disease in a mouse model where we can rapidly induce disease-associated tissue changes. Only the later-stage H. pylori strains could robustly colonize the diseased stomach environment. We also found that the ability to colonize the diseased stomach was associated with genetic variation in a putative cell surface adhesin gene called sabB . Additional experiments revealed that SabB promotes binding to stomach tissue and is critical for stomach colonization by the late-stage strains. Thus, H. pylori diversifies its genome during disease progression and these genomic changes highlight critical factors for bacterial persistence.

Background: For some vaccine-preventable diseases, the immunologic response to vaccination is altered by a pregnant state. The effect of pregnancy on SARS-CoV-2 vaccine response remains unclear., Objective: We sought to characterize the peak and longitudinal anti-S immunoglobulin G, immunoglobulin M, and immunoglobulin A responses to messenger RNA-based SARS-CoV-2 vaccination in pregnant persons and compare them with those in nonpregnant, reproductive-aged persons., Study Design: We conducted 2 parallel prospective cohort studies among pregnant and nonpregnant persons who received SARS-CoV-2 messenger RNA vaccinations. Blood was collected at the time of first and second vaccine doses, 2 weeks post second dosage, and with serial longitudinal follow-up up to 41.7 weeks post vaccination initiation. Anti-S immunoglobulin M, immunoglobulin G, and immunoglobulin A were analyzed by enzyme-linked immunosorbent assay. We excluded those with previous evidence of SARS-CoV-2 infection by history or presence of antinucleocapsid antibodies. In addition, for this study, we did not include individuals who received a third or booster vaccine dosage during the study period. We also excluded pregnant persons who were not fully vaccinated (14 days post receipt of the second vaccine dosage) by time of delivery and nonpregnant persons who became pregnant through the course of the study. We studied the effect of gestational age at vaccination on the anti-S response using Spearman correlation. We compared the peak anti-S antibody responses between pregnant and nonpregnant persons using a Mann-Whitney U test. We visualized and studied the longitudinal anti-S antibody response using locally weighted scatterplot smoothing, Mann-Whitney U test, and mixed analysis of variance test., Results: Data from 53 pregnant and 21 nonpregnant persons were included in this analysis. The median (interquartile range) age of the pregnant and nonpregnant participants was 35.0 (33.3-37.8) years and 36.0 (33.0-41.0) years, respectively. Six (11.3%) participants initiated vaccination in the first trimester, 23 (43.3%) in the second trimester, and 24 (45.3%) in the third trimester, with a median gestational age at delivery of 39.6 (39.0-40.0) weeks. The median (interquartile range) follow-up time from vaccine initiation to the last blood sample collected was 25.9 (11.9) weeks and 28.9 (12.9) weeks in the pregnant and nonpregnant cohort, respectively. Among pregnant persons, anti-S immunoglobulin G, immunoglobulin A, and immunoglobulin M responses were not associated with gestational age at vaccine initiation (all P>.05). The anti-S immunoglobulin G response at 2 weeks post second dosage was not statistically different between pregnant and nonpregnant persons (P>.05). However, the anti-S immunoglobulin M and immunoglobulin A responses at 2 weeks post second dosage were significantly higher in nonpregnant persons (P<.001 for both). The anti-S immunoglobulin G and immunoglobulin M levels 6 to 8 months after vaccine initiation fell to comparable proportions of the peak 2 weeks post second dosage antibody levels between pregnant and nonpregnant persons (immunoglobulin G P=.77; immunoglobulin M P=.51). In contrast, immunoglobulin A levels 6 to 8 months after vaccine initiation fell to statistically significantly higher proportions of peak 2 weeks post second dosage antibody levels in pregnant compared with nonpregnant persons (P=.002). Maternal anti-S immunoglobulin G levels were strongly correlated with umbilical cord anti-S immunoglobulin G levels (R=0.8, P<.001)., Conclusion: The anti-S immunoglobulin A, immunoglobulin M, and immunoglobulin G response to SARS-CoV-2 vaccination in pregnancy is independent of gestational age of vaccine initiation. Maintenance of the immunoglobulin G response is comparable between pregnant and nonpregnant persons. The differential peak response of immunoglobulin M and immunoglobulin A and the differential decline of anti-S immunoglobulin A between pregnant and nonpregnant persons requires further investigation., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Fusobacterium nucleatum (Fn) is a dominant bacterial species in colorectal cancer (CRC) tissue that is associated with cancer progression and poorer patient prognosis. Following a small-molecule inhibitor screen of 1,846 bioactive compounds against a Fn CRC isolate, we find that 15% of inhibitors are antineoplastic agents including fluoropyrimidines. Validation of these findings reveals that 5-fluorouracil (5-FU), a first-line CRC chemotherapeutic, is a potent inhibitor of Fn CRC isolates. We also identify members of the intratumoral microbiota, including Escherichia coli, that are resistant to 5-FU. Further, CRC E. coli isolates can modify 5-FU and relieve 5-FU toxicity toward otherwise-sensitive Fn and human CRC epithelial cells. Lastly, we demonstrate that ex vivo patient CRC tumor microbiota undergo community disruption after 5-FU exposure and have the potential to deplete 5-FU levels, reducing local drug efficacy. Together, these observations argue for further investigation into the role of the CRC intratumoral microbiota in patient response to chemotherapy., Competing Interests: Declaration of interests S.B is an inventor on US patent application no. PCT/US2018/042,966, submitted by the Broad Institute and DFCI, that covers targeting of Fusobacterium for treatment of CRC. K.D.L. is currently an employee at NanoString Technologies, Inc. A.B. is currently an employee at Bristol-Myers Squibb., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

The tumour-associated microbiota is an intrinsic component of the tumour microenvironment across human cancer types 1,2 . Intratumoral host-microbiota studies have so far largely relied on bulk tissue analysis 1-3 , which obscures the spatial distribution and localized effect of the microbiota within tumours. Here, by applying in situ spatial-profiling technologies 4 and single-cell RNA sequencing 5 to oral squamous cell carcinoma and colorectal cancer, we reveal spatial, cellular and molecular host-microbe interactions. We adapted 10x Visium spatial transcriptomics to determine the identity and in situ location of intratumoral microbial communities within patient tissues. Using GeoMx digital spatial profiling 6 , we show that bacterial communities populate microniches that are less vascularized, highly immuno‑suppressive and associated with malignant cells with lower levels of Ki-67 as compared to bacteria-negative tumour regions. We developed a single-cell RNA-sequencing method that we name INVADEseq (invasion-adhesion-directed expression sequencing) and, by applying this to patient tumours, identify cell-associated bacteria and the host cells with which they interact, as well as uncovering alterations in transcriptional pathways that are involved in inflammation, metastasis, cell dormancy and DNA repair. Through functional studies, we show that cancer cells that are infected with bacteria invade their surrounding environment as single cells and recruit myeloid cells to bacterial regions. Collectively, our data reveal that the distribution of the microbiota within a tumour is not random; instead, it is highly organized in microniches with immune and epithelial cell functions that promote cancer progression., (© 2022. The Author(s).)

Aberrant joint loading contributes to the development of posttraumatic knee osteoarthritis (PTOA) following anterior cruciate ligament reconstruction (ACLR); yet little is known about the association between joint loading due to daily walking and cartilage health post-ACLR. Accelerometer-based measures of daily steps and cadence (i.e., rate of steps/min) provide information regarding daily walking in a real-world setting. The purpose of this study was to determine the association between changes in serum cartilage oligomeric matrix protein (COMP; %∆COMP), a mechanosensitive biomarker that is associated with osteoarthritis progression, following a standardized walking protocol and daily walking in individuals with ACLR and uninjured controls. Daily walking was assessed over 7 days using an accelerometer worn on the right hip in 31 individuals with ACLR and 21 controls and quantified as mean steps/day and time spent in ≥100 steps/min. Serum COMP was measured before and following a 3000-step walking protocol at a preferred speed. %∆COMP was calculated as a change in COMP relative to the prewalking value. Linear regressions were used to examine associations between daily walking and %∆COMP after adjusting for preferred speed. Fewer daily steps (ΔR 2  = 0.18, p = 0.02) and fewer minutes spent in ≥100 steps/min (ΔR 2  = 0.16, p = 0.03) were associated with greater %∆COMP following walking in individuals with ACLR; no statistically significant associations existed in controls (daily steps: ΔR 2  = 0.03, p = 0.47; time ≥100 steps/min: ΔR 2  < 0.01, p = 0.81). Clinical significance: Individuals with ACLR who engage in less daily walking undergo greater %ΔCOMP, which may represent greater cartilage degradation or turnover in response to walking., (© 2022 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Many bacterial species are represented by a pan-genome, whose genetic repertoire far outstrips that of any single bacterial genome. Here we investigate how a bacterial pan-genome might influence gene essentiality and whether essential genes that are initially critical for the survival of an organism can evolve to become non-essential. By using Transposon insertion sequencing (Tn-seq), whole-genome sequencing and RNA-seq on a set of 36 clinical Streptococcus pneumoniae strains representative of >68% of the species' pan-genome, we identify a species-wide 'essentialome' that can be subdivided into universal, core strain-specific and accessory essential genes. By employing 'forced-evolution experiments', we show that specific genetic changes allow bacteria to bypass essentiality. Moreover, by untangling several genetic mechanisms, we show that gene essentiality can be highly influenced by and/or be dependent on: (1) the composition of the accessory genome, (2) the accumulation of toxic intermediates, (3) functional redundancy, (4) efficient recycling of critical metabolites and (5) pathway rewiring. While this functional characterization underscores the evolvability potential of many essential genes, we also show that genes with differential essentiality remain important antimicrobial drug target candidates, as their inactivation almost always has a severe fitness cost in vivo., (© 2022. The Author(s).)

Objective: People living with HIV (PLWH) frequently experience pain, which often co-occurs with psychological symptoms and may impact functional outcomes. We investigated cross-sectional associations between pain, depressive symptoms, and inflammation, and then explored whether pain was related to poorer physical function among older PLWH., Methods: We examined data from PLWH aged 54 to 78 years ( n = 162) recruited from a single outpatient program for a larger study on HIV and aging. Participants reported depressive symptoms (10-item Center for Epidemiological Studies Depression Scale) and then attended a biomedical visit in which they reported past-month pain (Medical Outcomes Study-HIV pain subscale), completed physical function assessments, and provided blood samples (assayed for interleukin 6, interferon-γ, tumor necrosis factor α, and C-reactive protein). Links between pain, depressive symptoms, inflammation, and physical function were tested using linear regression models., Results: PLWH with greater depressive symptoms experienced more pain than did those with fewer depressive symptoms ( B = 1.31, SE = 0.28, p < .001), adjusting for age, sex, race, body mass index, smoking, disease burden, time since HIV diagnosis, and medication use. Higher composite cytokine levels were associated with worse pain ( B = 5.70, SE = 2.54, p = .027 in adjusted model). Poorer physical function indicators, including slower gait speed, weaker grip strength, recent falls, and prefrail or frail status, were observed among those with worse pain. Exploratory mediation analyses suggested that pain may partially explain links between depressive symptoms and several physical function outcomes., Conclusions: Pain is a potential pathway linking depressive symptoms and inflammation to age-related health vulnerabilities among older PLWH; longitudinal investigation of this pattern is warranted. PLWH presenting with pain may benefit from multidisciplinary resources, including behavioral health and geriatric medicine approaches., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Psychosomatic Society.)

Efforts to cure HIV have focused on reactivating latent proviruses to enable elimination by CD8 + cytotoxic T-cells. Clinical studies of latency reversing agents (LRA) in antiretroviral therapy (ART)-treated individuals have shown increases in HIV transcription, but without reductions in virologic measures, or evidence that HIV-specific CD8 + T-cells were productively engaged. Here, we show that the SARS-CoV-2 mRNA vaccine BNT162b2 activates the RIG-I/TLR - TNF - NFκb axis, resulting in transcription of HIV proviruses with minimal perturbations of T-cell activation and host transcription. T-cells specific for the early gene-product HIV-Nef uniquely increased in frequency and acquired effector function (granzyme-B) in ART-treated individuals following SARS-CoV-2 mRNA vaccination. These parameters of CD8 + T-cell induction correlated with significant decreases in cell-associated HIV mRNA, suggesting killing or suppression of cells transcribing HIV. Thus, we report the observation of an intervention-induced reduction in a measure of HIV persistence, accompanied by precise immune correlates, in ART-suppressed individuals. However, we did not observe significant depletions of intact proviruses, underscoring challenges to achieving (or measuring) HIV reservoir reductions. Overall, our results support prioritizing the measurement of granzyme-B-producing Nef-specific responses in latency reversal studies and add impetus to developing HIV-targeted mRNA therapeutic vaccines that leverage built-in LRA activity., (© 2022. The Author(s).)

Background: Older people with HIV experience more comorbidities and geriatric syndromes than their HIV-negative peers, perhaps due to residual inflammation despite suppressive antiretroviral therapy. Cell-free mitochondrial DNA (cfmtDNA) released during necrosis-mediated cell death potentially acts as both mediator and marker of inflammatory dysregulation. Thus, we evaluated plasma cfmtDNA as a potential biomarker of geriatric syndromes., Methods: Participants underwent the Montreal Cognitive Assessment (MoCA), frailty testing, and measurement of plasma cfmtDNA by qPCR and inflammatory markers including C-reactive protein, interleukin-6 (IL-6), interferon gamma, and tumor necrosis factor alpha in this cross-sectional study., Results: Across 155 participants, the median age was 60 years (Q1, Q3: 56, 64), one-third were female, and 92% had HIV-1 viral load <200 copies/mL. The median MoCA score was 24 (21, 27). The plasma cfmtDNA level was higher in those with cognitive impairment (MoCA <23) ( P = 0.02 by the t test) and remained significantly associated with cognitive impairment in a multivariable logistic regression model controlling for age, sex, race, CD4 T-cell nadir, HIV-1 viremia, and depression. Two-thirds of participants met the criteria for a prefrail or frail state; higher plasma cfmtDNA was associated with slow walk and exhaustion but not overall frailty state. Cognitive dysfunction was not associated with C-reactive protein, IL-6, interferon gamma, or tumor necrosis factor alpha, and frailty state was only associated with IL-6., Conclusions: Plasma cfmtDNA may have a role as a novel biomarker of cognitive dysfunction and key components of frailty. Longitudinal investigation of cfmtDNA is warranted to assess its utility as a biomarker of geriatric syndromes in older people with HIV., Competing Interests: E.L.S., M.C.R., and Y.-S.Z. have no conflicts of interest. C.D.J is a consultant for TheraTechnologies. K.C.H. receives consulting fees from Faeth Therapeutics, Inc.; is on the review board for PESI, Inc.; and receives personal fees for reviewing professional nutrition education programing for PESI, Inc. The spouse of H.M.D.-V. holds employment at Elanco. The spouse of M.E.C. is a cofounder and shareholder and serves on the Scientific Advisory Board of Proterris, Inc. M.J.G. reports research support to the institution (Weill Cornell) from Gilead Sciences and Regeneron; is a consultant for Enzychem, Regeneron, ReAlta Life Sciences, and Sobi and receives royalties from Springer and UpToDate., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Long-term estimates of natural source zone depletion (NSZD) rates for petroleum LNAPL (light non-aqueous phase liquid) sites are not available. One-off measurements are often thought valid over the lifetime of LNAPL sites. In the context of site-wide LNAPL mass estimates, we report site-specific gasoline and diesel NSZD rates spanning 21-26 years. Using depth profiles of soil gases (oxygen, carbon dioxide, methane, volatiles) above LNAPL, NSZD rates were estimated in 1994, 2006 and 2020 for diesel and 1999, 2009 and 2020 for gasoline. Each date also had soil-core mass estimates, which together with NSZD rates allow estimation of the longevity for LNAPL presence. Site-wide coring (in 1992, 2002, 2007) estimated LNAPL mass reductions of 12,000 t. For diesel NSZD, the ratio of NSZD rates for 2006 (16,000-49,000 L/ha/y) to those in 2020 (2600-14,000 L/ha/y) was ~3-6. By 2020, the 1994 diesel NSZD rates would have predicted the entire removal of measured mass (16-42 kg/m 2 ). For gasoline, NSZD rates in 1999 were extremely high (50,000-270,000 L/ha/y) but 9-27 times lower (5800-10,000 L/ha/y) a decade later. The gasoline NSZD rates in 1999 predicted near complete mass removal in 2-12 years, but 10-11 kg/m 2 was measured 10 and 21 years later which is 26% of the initial mass in 1999. The outcomes substantiate the need to understand NSZD rate changes over the lifetime of LNAPL-impacted sites., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Research suggests that right-wing ideology is associated with negativity bias: a tendency to pay more attention and give more weight to negative versus positive stimuli. This work typically relies on either self-reported traits related to negativity bias in large, often-representative, samples or physiological and behavioural indicators of negativity bias in small convenience samples. We extend this literature and examine the relationship of negativity bias to political ideology using five distinct behavioural measures of negativity bias in four national samples of US residents with a total analytical sample size of about 4,000 respondents. We also examine the association of these behavioural measures to four of the most common self-report measures of personality in the literature on ideology. Across a wide range of tests, we find no consistent evidence for a relationship of negativity bias to either ideology or self-reported personality., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

We report the complete genome sequence of Morganella morganii CTX51T, a strain isolated from the resected tumor of a patient with cecal colorectal adenocarcinoma of the cecum. The genome comprises a circular chromosome of 4.19 Mbp, with an overall GC content of 50.4% and one circular plasmid of 8.48 kbp.

We report the complete genome sequence of Clostridium cadaveris IFB3C5, a strain isolated from the resected tumor of a treatment naive colorectal cancer patient. This genome is comprised of a singular chromosome of approximately 3.63 Mbp in length, contains two plasmids, and has an overall mean GC content of 31.7%.

Objectives: People living with human immunodeficiency virus (PLWH) treated with antiretrovirals have life spans similar to their HIV-negative peers. Yet, they experience elevated inflammation-related multimorbidity. Drawing on biopsychosocial determinants of health may inform interventions, but these links are understudied in older PLWH. We investigated cross-sectional relationships between psychosocial factors (mood, loneliness, and stigma), inflammatory markers, and age-related health outcomes among 143 PLWH aged 54-78 years., Method: Participants provided blood samples for serum cytokine and C-reactive protein (CRP) analyses, completed surveys assessing psychosocial factors and health, and completed frailty assessments. Regression models tested relationships between key psychosocial-, inflammation, and age-related health variables, adjusting for relevant sociodemographic and clinical factors., Results: Participants with more depressive symptoms had higher composite cytokine levels than those with fewer depressive symptoms (β = 0.22, t(126) = 2.71, p = .008). Those with higher cytokine levels were more likely to be prefrail or frail (adjusted odds ratio = 1.72, 95% confidence interval = 1.01-2.93) and reported worse physical function (β = -0.23, t(129) = -2.64, p = .009) and more cognitive complaints (β = -0.20, t(129) = -2.16, p = .03) than those with lower cytokine levels. CRP was not significantly related to these outcomes; 6-month fall history was not significantly related to inflammatory markers., Discussion: Novel approaches are needed to manage comorbidities and maximize quality of life among older PLWH. Illustrating key expected biopsychosocial links, our findings highlight several factors (e.g., depressive symptoms, poorer physical function) that may share bidirectional relationships with chronic inflammation, a key factor driving morbidity. These links may be leveraged to modify factors that drive excessive health risk among older PLWH., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We report the complete genome of Arachnia rubra strain DSM 100122 T . The genome is 3.32 Mb, with a GC content of 64.2%. The genome contains 3,005 predicted genes, including 2,923 predicted protein-coding genes.