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This study examined whether meaningful work may improve one's quality of life outside of the workplace (i.e., work-to-life enrichment). More importantly, we proposed and tested competing hypotheses regarding the role of work engagement in the relationship between meaningful work and work-to-life enrichment. Specifically, we investigated whether work engagement served as a mediator of this relationship, as suggested by the job demands-resources model, or instead a moderator, as suggested by conservation of resources theory. Two-wave survey data were collected from 194 respondents recruited via Amazon Mechanical Turk. Analyses showed that meaningful work was positively related to work-to-life enrichment over time (i.e., 3 months later). Additionally, work engagement mediated but did not moderate the relationship between meaningful work at Time 1 and work-to-life enrichment at Time 2. We suggest that organizations foster a sense of meaningfulness in employees to facilitate engagement and in turn enrich employees' lives beyond the workplace. Therefore, not only organizations, but individuals as well may reap the benefits of meaningful work. [ABSTRACT FROM AUTHOR]

There is much interest in the Hierarchical Dirichlet Process Hidden Markov Model (HDP-HMM) as a natural Bayesian nonparametric extension of the ubiquitous Hidden Markov Model for learning from sequential and time-series data. However, in many settings the HDP-HMM's strict Markovian constraints are undesirable, particularly if we wish to learn or encode non-geometric state durations. We can extend the HDP-HMM to capture such structure by drawing upon explicit-duration semi-Markov modeling, which has been developed mainly in the parametric non-Bayesian setting, to allow construction of highly interpretable models that admit natural prior information on state durations. In this paper we introduce the explicit-duration Hierarchical Dirichlet Process Hidden semi- Markov Model (HDP-HSMM) and develop sampling algorithms for efficient posterior inference. The methods we introduce also provide new methods for sampling inference in the finite Bayesian HSMM. Our modular Gibbs sampling methods can be embedded in samplers for larger hierarchical Bayesian models, adding semi-Markov chain modeling as another tool in the Bayesian inference toolbox. We demonstrate the utility of the HDP-HSMM and our inference methods on both synthetic and real experiments. [ABSTRACT FROM AUTHOR]

Aim: The objective of the study was to evaluate the effect of the Erbium-Yttrium aluminum garnet (YAG) laser on diabetic foot ulcer that had not responded to standard care. Methods: We retrospectively evaluated 23 patients with c non-healing diabetic foot ulcers that received at least four weeks of standard wound care, demonstrated poor healing response, and were subsequently treated with YAG laser. We measure the percent wound area reduction (PWAR) for the 4 weeks prior to initiating laser therapy and the PWAR for 4 weeks following the initiation of laser therapy. YAG laser treatment consisted of two components: debridement and re-surfacing. The laser settings were the same for all treatments. We used pair t-test to compare pre versus post wound area reduction. Results: During the 4-week period prior to the initiation of laser therapy, the average PWAR was -32.1%. During this time, the diabetic foot ulcers increased in area. After treatment with YAG laser, after 4 weeks the average PWAR was 63.5% (p<0.01), 66.7%% of patients had > 50% PAR at 4 weeks and 45.8% of patients healed by 12 weeks. Conclusion: YAG laser therapy accelerated DFU healing in a cohort of patients with ulcers that had been unresponsive to standard of care therapy. Disclosure: M.J. Johnson: None. L.A. Lavery: Consultant; Self; Bayer US, Boehringer Ingelheim Pharmaceuticals, Inc., Medline Industries, Inc. Research Support; Self; Cardinal Health, EO2 Concepts, Integra LifeSciences, MedImmune, Osiris Therapeutics, Inc. [ABSTRACT FROM AUTHOR]

The goal of an effective AIDS vaccine is to generate immunity that will prevent human immunodeficiency virus 1 (HIV-1) acquisition. Despite limited progress toward this goal, renewed optimism has followed the recent success of the RV144 vaccine trial in Thailand. However, the lack of complete protection in this trial suggests that breakthroughs, where infection occurs despite adequate vaccination, will be a reality for many vaccine candidates. We previously reported that neutralizing antibodies elicited by DNA prime-recombinant adenovirus serotype 5 (rAd5) boost vaccination with simian immunodeficiency virus strain mac239 (SIVmac239) Gag-Pol and Env provided protection against pathogenic SIVsmE660 acquisition after repeated mucosal challenge. Here, we report that SIV-specific CD8+ T cells elicited by that vaccine lowered both peak and set-point viral loads in macaques that became infected despite vaccination. These SIV-specific CD8+ T cells showed strong virus-inhibitory activity (VIA) and displayed an effector memory (EM) phenotype. VIA correlated with high levels of CD107a mobilization and perforin expression in SIV-specific CD8+ T cells. Remarkably, both the frequency and the number of Gag CM9-specific public clonotypes were strongly correlated with VIA mediated by EM CD8+ T cells. The ability to elicit such virus-specific EM CD8+ T cells might contribute substantially to an efficacious HIV/AIDS vaccine, even after breakthrough infection. [ABSTRACT FROM AUTHOR]

Aims: To determine the degree patients with diabetic foot ulcers, Charcot neuroarthropathy and neuropathic fractures and dislocations fear complications (death, dialysis, heart attack, stroke, blindness, diabetic foot infection, minor and major lower extremity amputation [LEA]) that can occur and to assess if there is a difference between fears of patients with diabetic foot ulcers, Charcot neuroarthropathy and neuropathic fractures and dislocations and diabetic patients without these complications.Methods: 478 patients completed an eight question Likert scale survey. The study group was defined as non-infected foot ulcers, neuropathic fractures and Charcot neuroarthropathy.Results: Of the 478 patients, 121 (25.3 %) had diabetic foot ulcers, Charcot neuroarthropathy or neuropathic fractures and dislocations and 357 (74.7 %) did not. The study group had significantly higher odds of reporting extreme fear of foot infection (OR 2.8, 95 % CI 1.8-4.5), major LEA (OR 2.8, 95 % CI 1.8-4.4), minor LEA (OR 2.3, 95 % CI 1.5-3.5), blindness (OR 2.0, 95 % CI 1.3-3.2), dialysis (OR 2.0, 95 % CI 1.1-3.3), and death (OR 2.4, 95 % CI 1.4-4.2). In the study group highest rated fear measures were foot infection (3.71, SD 1.23), minor amputation (3.67, SD 1.45) and major amputation (3.63, SD 1.52). There were no significant differences in the mean fear of infection, minor amputation or major amputation.Conclusion: Patients with diabetic foot ulcers, Charcot neuroarthropathy or neuropathic fractures and dislocations reported higher fear ratings of diabetes-related complications compared to those without these complications. [ABSTRACT FROM AUTHOR]

DNA replication stress is one of the primary causes of genome instability. In response to replication stress, cells can employ replication restart mechanisms that rely on homologous recombination to resume replication fork progression and preserve genome integrity. In this review, we provide an overview of various methods that have been developed to induce site-specific replication fork stalling or collapse in eukaryotic cells. In particular, we highlight recent studies of mechanisms of replication-associated recombination resulting from site-specific protein-DNA barriers and single-strand breaks, and we discuss the contributions of these findings to our understanding of the consequences of these forms of stress on genome stability., 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 B.V. All rights reserved.)

Little is known regarding outcomes of talus fracture management among patients with diabetes mellitus. This study aimed to compare post-operative outcomes after open reduction and internal fixation for talus fracture in patients with complicated diabetes, uncomplicated diabetes, and patients without diabetes. We used the PearlDiver database to identify patients who underwent operative repair of talus fractures from 2009 to 2021. Complications were evaluated at 30-days, 90-days, and 1 year of surgery. As we performed multiple separate analyses, to minimize the risk of type 1 error we employed the Bonferroni correction for statistical significance (p< 0.017). The PearlDiver identified 5,232 patients with talus fracture that underwent open reduction internal fixation. Stratified by diabetes status, the "complicated diabetes," "uncomplicated diabetes," and "no diabetes" groups contained 223, 418, and 4591 patients, respectively. Reoperation, acute kidney injury, and myocardial infarction were increased among diabetes patients compared to non-diabetes patients, irrespective of diabetes severity within 3 months of surgery. Furthermore, patients with complicated diabetes were more likely to develop sepsis and wound disruption compared to their non-diabetes counterparts within 3 months. While not statistically significant, complicated diabetes patients were diagnosed with talar non-union at higher rates compared with non-diabetes patients. Further analysis may reveal a clinically significant discrepancy in non-union between these groups. Complicated diabetes is associated with significantly higher risk of multiple adverse events following talus fracture repair. LEVEL OF CLINICAL EVIDENCE: 3., (Copyright © 2024. Published by Elsevier Inc.)

Abstract: Tendero-Ortiz, E, Johnson, MJ, Horsfall, CM, Vondrasek, JD, Grosicki, GJ, Riemann, BL, and Flatt, AA. Tournament recovery profiles and physical demands in a collegiate women's tennis team. J Strength Cond Res XX(X): 000-000, 2024-We aimed to characterize recovery profiles and tournament physical demands in women's collegiate tennis players. A Division 1 team (n = 9) participated in the study. Markers of cardiac autonomic (resting heart rate [HR], HR variability), neuromuscular (isometric handgrip strength, seated single-arm shot-put test [SSAPT], hexagon agility, countermovement jump characteristics), and perceptual recovery were obtained before the tournament (baseline) and again 1 and 2 days posttournament. Cardiorespiratory (HR) and movement characteristics from matches were quantified with wearable devices. p values < 0.05 were statistically significant. No recovery markers differed from baseline (ps > 0.05), although small effect size reductions 1 day posttournament were noted for SSAPT, hexagon agility, and select countermovement jump characteristics. In addition, hexagon agility times and SSAPT were slower (p < 0.01) and shorter (p < 0.05), respectively, at 1 versus 2 days posttournament. Similarly, relative to 1 day posttournament, perceptual makers were improved 2 days posttournament (ps < 0.05). Mean and peak HR were higher for singles versus doubles matches  (ps < 0.05). Except for average speed, movement parameters were greater during singles versus doubles matches (ps < 0.05). Markers of recovery were minimally affected 1 day posttournament relative to baseline, but perceptual and select neuromuscular markers were most improved 2 days posttournament. Thus, passive rest or limited intensity training 1 day posttournament seems advisable. Competition HR and movement profiles inform practitioners of the cardiorespiratory and locomotor demands of women's collegiate tennis, which may be useful in designing preparatory conditioning programs to ensure that players attain match-specific physical capacities in training before competition., (Copyright © 2024 National Strength and Conditioning Association.)

Single-strand breaks (SSBs) are one of the most common endogenous lesions and have the potential to give rise to cytotoxic double-strand breaks (DSBs) during DNA replication. To investigate the mechanism of replication fork collapse at SSBs and subsequent repair, we employed Cas9 nickase (nCas9) to generate site and strand-specific nicks in the budding yeast genome. We show that nCas9-induced nicks are converted to mostly double-ended DSBs during S-phase. We find that repair of replication-dependent DSBs requires homologous recombination (HR) and is independent of canonical non-homologous end joining. Consistent with a strong bias to repair these lesions using a sister chromatid template, we observe minimal induction of inter-chromosomal HR by nCas9. Using nCas9 and a gRNA to nick either the leading or lagging strand template, we carried out a genome-wide screen to identify factors necessary for the repair of replication-dependent DSBs. All the core HR genes were recovered in the screen with both gRNAs, but we recovered components of the replication-coupled nucleosome assembly (RCNA) pathway with only the gRNA targeting the leading strand template. By use of additional gRNAs, we find that the RCNA pathway is especially important to repair a leading strand fork collapse.

Rigid flatfoot deformity with valgus ankle instability is a complex condition to treat. Thorough clinical and radiographic evaluation is vital to determine treatment strategies. Nonoperative treatment usually relies on bracing or various orthoses. Surgical interventions include ligament reconstruction, osteotomies, arthrodesis, arthroplasty, or a combination of these procedures. Before addressing the ankle deformity, a plantigrade foot is important so a staged approach may be necessary. Misalignment of the ankle replacement can lead to edge loading and early failure. As the implants and our understanding of ankle arthroplasty improve, more patients may benefit from a motion-preserving procedure rather than an arthrodesis., (Published by Elsevier Inc.)

Refractory pain to the fourth and fifth tarsometatarsal (TMT) joint can be a source of disability and functional impairment. While pain has been attributed to injury, post-traumatic arthritis, arthrofibrosis, the principal causes of pain in the absence of arthritis are not well elucidated. The purpose of this study is to characterize arthroscopic pathology associated with chronic refractory pain to the fourth and fifth TMT joints. We retrospectively examined 24 patients that underwent arthroscopic surgery of the fourth and fifth TMT joints for refractory pain at our academic institution between 2015 and 2019. We used the Outerbridge classification for chondral lesions, the Kellgren Lawrence radiographic classification for osteoarthritis, and described intraarticular pathologies as acute hypertrophic synovitis, chronic synovial fibrosis, hyaline bands, meniscoid bodies, loose joint bodies, arthrofibrosis. Approximately, 31 of 45 TMT joints (68.9%) presented with radiographic evidence of arthritis. Approximately, 14 of 45 TMT joints (31.11%) were absent of radiographic signs of arthritis. The frequency of soft tissue pathology seen in these patients without radiographic evidence of arthritis was arthrofibrosis (87.5%), chronic synovial fibrosis (75.0%), and acute hypertrophic synovitis (62.5%). This is the first study to report arthroscopic pathologies associated with refractory pain to the fourth and fifth TMT joints., (Published by Elsevier Inc.)

Charcot neuroarthropathy can cause severe deformity of the midfoot, and intramedullary use of beams and bolts has been utilized as a method of definitive stabilization. This systematic review evaluated the outcomes of intramedullary beaming in patients with Charcot neuroarthropathy and determined the methodological quality of the studies. Four online databases were searched: PubMed, MEDLINE (Clarivate Analytics), CINAHL (Cumulative Index to Nursing and Allied Health) and Web of Science (Clarivate Analytics). To assess the methodological quality of the studies, the Coleman Methodology Score was used. The data was pooled into 2 outcomes groups for comparison: (1) Studies that reported on the outcomes of Charcot specific implants (study group). (2) Studies that reported on the outcomes using non-Charcot specific implants (control group). After screening, 16 studies were included. Compared to our control group, our study group had significantly higher rates of overall hardware complications, hardware migration, surgical site infection, reoperation, and nonunion. The study group had significantly lower rates of limb salvage compared to the control group. Our study and control groups did not differ in the rates of hardware breakage, wound healing complications, or mortality. The limb salvage rate was 92% and 97% of patients were still alive at a mean follow-up of 25 months. The mean Coleman Methodology Score indicated the quality of the studies was poor and consistent with methodologic limitations. The quality of published studies on intramedullary implants for Charcot reconstruction is low. Complications when utilizing intramedullary fixation for Charcot reconstruction are high, whether or not Charcot specific implants are used., (Copyright © 2022. Published by Elsevier Inc.)

Background: Adoptive transfer of tumor-infiltrating lymphocytes (TIL) fails to consistently elicit tumor rejection. Manipulation of intrinsic factors that inhibit T cell effector function and neoantigen recognition may therefore improve TIL therapy outcomes. We previously identified the cytokine-induced SH2 protein (CISH) as a key regulator of T cell functional avidity in mice. Here, we investigate the mechanistic role of CISH in regulating human T cell effector function in solid tumors and demonstrate that CRISPR/Cas9 disruption of CISH enhances TIL neoantigen recognition and response to checkpoint blockade., Methods: Single-cell gene expression profiling was used to identify a negative correlation between high CISH expression and TIL activation in patient-derived TIL. A GMP-compliant CRISPR/Cas9 gene editing process was developed to assess the impact of CISH disruption on the molecular and functional phenotype of human peripheral blood T cells and TIL. Tumor-specific T cells with disrupted Cish function were adoptively transferred into tumor-bearing mice and evaluated for efficacy with or without checkpoint blockade., Findings: CISH expression was associated with T cell dysfunction. CISH deletion using CRISPR/Cas9 resulted in hyper-activation and improved functional avidity against tumor-derived neoantigens without perturbing T cell maturation. Cish knockout resulted in increased susceptibility to checkpoint blockade in vivo., Conclusions: CISH negatively regulates human T cell effector function, and its genetic disruption offers a novel avenue to improve the therapeutic efficacy of adoptive TIL therapy., Funding: This study was funded by Intima Bioscience, U.S. and in part through the Intramural program CCR at the National Cancer Institute., Competing Interests: Declaration of interests M.C. is a co-founder of Intima Bioscience. B.R.W., S.A.R., and B.S.M. have received sponsored research support from Intima Bioscience. D.C.P., B.R.W., M.C., S.A.R., B.S.M., and N.P.R. have patents filed based on the findings described here., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

There is a paucity of literature characterizing risk factors for nonunion associated with the modified Lapidus procedure for correction of hallux valgus. The purpose of this study was to evaluate risk factors associated with nonunion for Lapidus bunionectomies. Patients who underwent modified Lapidus procedure from 2009 to 2018 were retrospectively reviewed. Patient's age, sex, body mass index, prior bunionectomy, history of tobacco use, presence of diabetes mellitus or hypothyroidism, and fixation method were recorded along with pre- and postoperative radiographic parameters. A multiple logistic regression analysis was implemented to estimate the odds of nonunion. Of the 222 patients who met inclusion criteria, nonunion with modified Lapidus procedure was observed in 20 patients (9.01%). Odds of nonunion with modified Lapidus procedure were greater for patients who had undergone previous bunionectomy (odds ratio [OR] = 3.957, 95% confidence interval [CI]: 1.021-15.338), as body mass index increased (OR = 1.091, 95% CI: 1.018-1.170), and as preoperative HV angle increased (OR = 1.108, 95% CI: 1.020-1.203). Odds of nonunion were lower for patients as preoperative intermetatarsal angle increased (OR = 0.739, 95% CI: 0.580-0.941). No significant increased odds of nonunion were found between fixation methods., (Copyright © 2022 the American College of Foot and Ankle Surgeons. All rights reserved.)

Diabetic foot infections (DFI) are an increasingly common cause of hospitalizations. Once hospitalized with DFI, many patients require some level of amputation, often undergoing multiple operations. With increasing importance on patient-centered metrics, self-reported health-related quality of life (HRQOL) tools have been developed. This prospective cohort study aimed assessed the impact of DFI on HRQOL. Two hundred twenty-four patients completed the 29-item Patient-Reported Outcome Measurement Information System (PROMIS) and 12-Item Short Form (SF-12) survey. Secondary outcomes using the Foot and Ankle Ability Measures survey were obtained and included in the analysis. The study group was comprised of hospitalized patients with DFIs (n = 120), and the control group was comprised of patients with diabetes who were evaluated for routine outpatient foot care (n = 104); diabetic foot screening, wound care, onychomycosis, and/or callosities. Using this cohort, a propensity score-matched sample of hospitalized patients with DFI (n = 35) and control group patients (n = 35) was created for comparative analysis. The 2-independent sample t test was used to test for group differences on each of the PROMIS subscale outcomes. Using PROMIS, we found that hospitalized patients with DFI reported significantly worse HRQOL in 6 of 7 subscales (physical function, anxiety, depression, fatigue, social role, pain intensity; p value range: .0001-.02) compared to outpatients with diabetes evaluated for routine foot care. There was no significant difference between the 2 groups on sleep disturbance (p = .22). Patients hospitalized for DFI report lower HRQOL compared to patients with diabetes receiving routine outpatient foot care., (Copyright © 2021 the American College of Foot and Ankle Surgeons. All rights reserved.)

Social influences may create a barrier to couples HIV testing and counselling (CHTC) uptake in sub-Saharan Africa. This secondary analysis of data collected in the 'Uthando Lwethu' randomised controlled trial used discrete-time survival models to evaluate the association between within-couple average 'peer support' score and uptake of CHTC by the end of nine months' follow-up. Peer support was conceptualised by self-rated strength of agreement with two statements describing friendships outside of the primary partnership. Eighty-eight couples (26.9%) took up CHTC. Results tended towards a dichotomous trend in models adjusted only for trial arm, with uptake significantly less likely amongst couples in the higher of four peer support score categories (OR 0.34, 95% CI 0.18, 0.68 [7-10 points]; OR 0.53, 95% CI 0.28, 0.99 [≥ 11 points]). A similar trend remained in the final multivariable model, but was no longer significant (AOR 0.59, 95% CI 0.25, 1.42 [7-10 points]; AOR 0.88, 95% CI 0.36, 2.10 [≥ 11 points]). Accounting for social influences in the design of couples-focused interventions may increase their success., (© 2021. The Author(s).)

The yeast INO80 chromatin remodeling complex plays essential roles in regulating DNA damage repair, replication, and promoter architecture. INO80's role in these processes is likely related to its ability to slide nucleosomes, but the underlying mechanism is poorly understood. Here we use ensemble and single-molecule enzymology to study INO80-catalyzed nucleosome sliding. We find that the rate of nucleosome sliding by INO80 increases ∼100-fold when the flanking DNA length is increased from 40 to 60 bp. Furthermore, once sliding is initiated, INO80 moves the nucleosome rapidly at least 20 bp without pausing to re-assess flanking DNA length, and it can change the direction of nucleosome sliding without dissociation. Finally, we show that the Nhp10 module of INO80 plays an auto-inhibitory role, tuning INO80's switch-like response to flanking DNA. Our results indicate that INO80 is a highly processive remodeling motor that is tightly regulated by both substrate cues and non-catalytic subunits., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The goal of an effective AIDS vaccine is to generate immunity that will prevent human immunodeficiency virus 1 (HIV-1) acquisition. Despite limited progress toward this goal, renewed optimism has followed the recent success of the RV144 vaccine trial in Thailand. However, the lack of complete protection in this trial suggests that breakthroughs, where infection occurs despite adequate vaccination, will be a reality for many vaccine candidates. We previously reported that neutralizing antibodies elicited by DNA prime-recombinant adenovirus serotype 5 (rAd5) boost vaccination with simian immunodeficiency virus strain mac239 (SIVmac239) Gag-Pol and Env provided protection against pathogenic SIVsmE660 acquisition after repeated mucosal challenge. Here, we report that SIV-specific CD8(+) T cells elicited by that vaccine lowered both peak and set-point viral loads in macaques that became infected despite vaccination. These SIV-specific CD8(+) T cells showed strong virus-inhibitory activity (VIA) and displayed an effector memory (EM) phenotype. VIA correlated with high levels of CD107a mobilization and perforin expression in SIV-specific CD8(+) T cells. Remarkably, both the frequency and the number of Gag CM9-specific public clonotypes were strongly correlated with VIA mediated by EM CD8(+) T cells. The ability to elicit such virus-specific EM CD8(+) T cells might contribute substantially to an efficacious HIV/AIDS vaccine, even after breakthrough infection.