Incidence of Venous Thromboembolism after Primary Total Hip Arthroplasty with Mechanical Prophylaxis in Hong Kong Chinese.

Purpose: The incidence of deep vein thrombosis (DVT) following total hip arthroplasty (THA) without chemoprophylaxis could be as high as 50% in Caucasians. However, according to several subsequent studies, the incidence of venous thromboembolic events (VTE) in Asians was much lower. The routine use of chemoprophylaxis, which could potentially cause increased bleeding, infection, and wound complications, has been questioned in low-incidence populations. The objective of this study is to determine the incidence of VTE after primary THA without chemoprophylaxis in an Asian population using a fast-track rehabilitation protocol and to verify the safety profile for use of 'mechanical prophylaxis alone' in patients with standard risk of VTE. Materials and Methods: This is a retrospective cohort study of 542 Hong Kong Chinese patients who underwent primary THA without chemoprophylaxis. All patients received intermittent pneumatic compression and graduated compression stockings as mechanical prophylaxis. Multimodal pain management was applied in order to facilitate early mobilisation. Routine duplex ultrasonography was performed between the fourth and seventh postoperative day for detection of proximal DVT. Results: All patients were Chinese (mean age, 63.0±11.9 years). Six patients developed proximal DVT (incidence rate, 1.1%). None of the patients had symptomatic or fatal pulmonary embolism. Conclusion: The incidence of VTE after primary THA without chemical prophylaxis can be low in Asian populations when following a fast-track rehabilitation protocol. Mechanical prophylaxis alone can be regarded as a reasonably safe practice in terms of a balanced benefit-to-risk ratio for Asian patients with standard risk of VTE.

The mediating roles of supervisor anger and envy in linking subordinate performance to abusive supervision: A curvilinear examination.

This research aims to understand why both low and high subordinate performance can induce abusive supervision. Drawing on the framework of affective events theory and research on anger and envy, we posit that low performance incurs abuse due to supervisor anger, whereas high performance elicits abuse due to supervisor envy. More specifically, subordinate performance has a decreasing curvilinear relationship with supervisor anger (i.e., a negative effect that gradually dissipates) and an increasing curvilinear relationship with supervisor envy (i.e., a positive effect that gradually emerges). Through supervisor anger and envy, subordinate performance therefore presents different curvilinear indirect relationships with abusive supervision. The results from two vignette-based experiments and a multiwave, multisource field study support these hypotheses. We further find that supervisor comparison orientation augments the curvilinear emergence of supervisor envy and ensuing abuse in response to higher subordinate performance. However, regardless of their level of performance orientation, supervisors are prone to higher anger and subsequent abusive supervision in response to lower subordinate performance. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Endocytic Motif on a Biotin-Tagged HIV-1 Env Modulates the Co-Transfer of Env and Gag during Cell-to-Cell Transmission.

During HIV-1 transmission through T cell virological synapses, the recruitment of the envelope (Env) glycoprotein to the site of cell-cell contact is important for adhesion and for packaging onto nascent virus particles which assemble at the site. Live imaging studies in CD4 T cells have captured the rapid recruitment of the viral structural protein Gag to VSs. We explored the role of endocytic trafficking of Env initiated by a membrane proximal tyrosine motif during HIV transfer into target cells and examined the factors that allow Gag and Env to be transferred together across the synapse. To facilitate tracking of Env in live cells, we adapted an Env tagging method and introduced a biotin acceptor peptide (BAP) into the V4 loop of Env gp120, enabling sensitive fluorescent tracking of V4-biotinylated Env. The BAP-tagged and biotinylated HIVs were replication-competent in cell-free and cell-to-cell infection assays. Live cell fluorescent imaging experiments showed rapid internalized cell surface Env on infected cells. Cell-cell transfer experiments conducted with the Env endocytosis mutant (Y712A) showed increased transfer of Env. Paradoxically, this increase in Env transfer was associated with significantly reduced Gag transfer into target cells, when compared to viral transfer associated with WT Env. This Y712A Env mutant also exhibited an altered Gag/biotin Env fluorescence ratio during transfer that correlated with decreased productive cell-to-cell infection. These results may suggest that the internalization of Env into recycling pools plays an important role in the coordinated transfer of Gag and Env across the VS, which optimizes productive infection in target cells.

Preclinical studies of efficacy thresholds and tolerability of a clinically ready lentiviral vector for pyruvate kinase deficiency treatment.

Pyruvate kinase deficiency (PKD) is a rare autosomal recessive disorder caused by mutations in the PKLR gene. PKD is characterized by non-spherocytic hemolytic anemia of variable severity and may be fatal in some cases during early childhood. Although not considered the standard of care, allogeneic stem cell transplantation has been shown as a potentially curative treatment, limited by donor availability, toxicity, and incomplete engraftment. Preclinical studies were conducted to define conditions to enable consistent therapeutic reversal, which were based on our previous data on lentiviral gene therapy for PKD. Improvement of erythroid parameters was identified by the presence of 20%-30% healthy donor cells. A minimum vector copy number (VCN) of 0.2-0.3 was required to correct PKD when corrected cells were transplanted in a mouse model for PKD. Biodistribution and pharmacokinetics studies, with the aim of conducting a global gene therapy clinical trial for PKD patients (RP-L301-0119), demonstrated that genetically corrected cells do not confer additional side effects. Moreover, a clinically compatible transduction protocol with mobilized peripheral blood CD34+ cells was optimized, thus facilitating the efficient transduction on human cells capable of repopulating the hematopoiesis of immunodeficient mice. We established conditions for a curative lentiviral vector gene therapy protocol for PKD.

Tibial tray thickness does not significantly increase medial tibial bone resorption: Using tibial bone density as an objective measurement method.

BACKGROUND: Recent studies have reported the occurrence of medial tibial bone resorption following total knee replacement. One study proposed that a thick tibial tray results in stress shielding and increases the risk of bone resorption, but its findings were based on subjective radiological assessment. This study aimed to verify this hypothesis and to objectively quantify medial tibial bone density by using serial measurements with digital radiological densitometry. METHODS: This was a retrospective cohort study involving 140 patients (70 thick tray vs. 70 thin tray) with cobalt-chromium implants with at least 24 months of follow-up. Standard radiographs were reviewed to look for incidence of medial tibial bone loss. Serial measurement of medial tibial bone density was also performed using the method of digital radiological densitometry. RESULTS: There was no significant difference in the incidence of medial tibial bone loss. Both groups showed a significant drop in medial tibial bone density after operation (P < 0.01). Medial tibial bone density of the thick-tray cohort was significantly higher than the thin-tray cohort at one year (93.3 vs. 83.1 Greyscale; P = 0.04), but not at two and three years. Clinical outcomes in terms of postoperative range of motion, Knee Society score and complication rates were similar. CONCLUSIONS: Medial tibial bone resorption is a common phenomenon. Implants with thicker tibial trays suffer less than those with thinner trays at one year, but the difference is transient and does not affect clinical outcome.

Induction of human hemogenesis in adult fibroblasts by defined factors and hematopoietic coculture.

Transcription factor (TF)-based reprogramming of somatic tissues holds great promise for regenerative medicine. Previously, we demonstrated that the TFs GATA2, GFI1B, and FOS convert mouse and human fibroblasts to hemogenic endothelial-like precursors that generate hematopoietic stem progenitor (HSPC)-like cells over time. This conversion is lacking in robustness both in yield and biological function. Herein, we show that inclusion of GFI1 to the reprogramming cocktail significantly expands the HSPC-like population. AFT024 coculture imparts functional potential to these cells and allows quantification of stem cell frequency. Altogether, we demonstrate an improved human hemogenic induction protocol that could provide a valuable human in vitro model of hematopoiesis for disease modeling and a platform for cell-based therapeutics. DATABASE: Gene expression data are available in the Gene Expression Omnibus (GEO) database under the accession number GSE130361.

It's mine! Psychological ownership of one's job explains positive and negative workplace outcomes of job engagement.

Job engagement denotes the extent to which an employee invests the full self in performing the job. Extant research has investigated the positive outcomes of job engagement, paying little attention to its potential costs to the organizations. Integrating the extended self theory and the literature on psychological ownership as our overarching theoretical framework, we develop and test the double-edged effects of job engagement on workplace outcomes through the mediating role of job-based psychological ownership. Analyses of two survey studies with multisource multiphase data support that job engagement can lead to positive workplace outcomes including in-role performance and organizational citizenship behaviors (OCBs) through job-based psychological ownership. At the same time, job engagement is also positively related to negative workplace outcomes including territorial behavior, knowledge hiding, and pro-job unethical behavior through the same mechanism of job-based psychological ownership. These indirect effects of job engagement on negative work outcomes are amplified by employees' avoidance motivation. The theoretical and practical implications are discussed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Cooperative Transcription Factor Induction Mediates Hemogenic Reprogramming.

During development, hematopoietic stem and progenitor cells (HSPCs) arise from specialized endothelial cells by a process termed endothelial-to-hematopoietic transition (EHT). The genetic program driving human HSPC emergence remains largely unknown. We previously reported that the generation of hemogenic precursor cells from mouse fibroblasts recapitulates developmental hematopoiesis. Here, we demonstrate that human fibroblasts can be reprogrammed into hemogenic cells by the same transcription factors. Induced cells display dynamic EHT transcriptional programs, generate hematopoietic progeny, possess HSPC cell surface phenotype, and repopulate immunodeficient mice for 3 months. Mechanistically, GATA2 and GFI1B interact and co-occupy a cohort of targets. This cooperative binding is reflected by engagement of open enhancers and promoters, initiating silencing of fibroblast genes and activating the hemogenic program. However, GATA2 displays dominant and independent targeting activity during the early phases of reprogramming. These findings shed light on the processes controlling human HSC specification and support generation of reprogrammed HSCs for clinical applications.

Enhanced FCGR2A and FCGR3A signaling by HIV viremic controller IgG.

HIV-1 viremic controllers (VC) spontaneously control infection without antiretroviral treatment. Several studies indicate that IgG Abs from VCs induce enhanced responses from immune effector cells. Since signaling through Fc-γ receptors (FCGRs) modulate these Ab-driven responses, here we examine if enhanced FCGR activation is a common feature of IgG from VCs. Using an infected cell-based system, we observed that VC IgG stimulated greater FCGR2A and FCGR3A activation as compared with noncontrollers, independent of the magnitude of HIV-specific Ab binding or virus neutralization activities. Multivariate regression analysis showed that enhanced FCGR signaling was a significant predictor of VC status as compared with chronically infected patients (CIP) on highly active antiretroviral therapy (HAART). Unsupervised hierarchical clustering of patient IgG functions primarily grouped VC IgG profiles by enhanced FCGR2A, FCGR3A, or dual signaling activity. Our findings demonstrate that enhanced FCGR signaling is a common and significant predictive feature of VC IgG, with VCs displaying a distinct spectrum of FCGR activation profiles. Thus, profiling FCGR activation may provide a useful method for screening and distinguishing protective anti-HIV IgG responses in HIV-infected patients and in monitoring HIV vaccination regimens.

Visualization of HIV T Cell Virological Synapses and Virus-Containing Compartments by Three-Dimensional Correlative Light and Electron Microscopy.

Virological synapses (VS) are adhesive structures that form between infected and uninfected cells to enhance the spread of HIV-1. During T cell VS formation, viral proteins are actively recruited to the site of cell-cell contact where the viral material is efficiently translocated to target cells into heterogeneous, protease-resistant, antibody-inaccessible compartments. Using correlative light and electron microscopy (CLEM), we define the membrane topography of the virus-containing compartments (VCC) where HIV is found following VS-mediated transfer. Focused ion beam scanning electron microscopy (FIB-SEM) and serial sectioning transmission electron microscopy (SS-TEM) were used to better resolve the fluorescent Gag-containing structures within the VCC. We found that small punctate fluorescent signals correlated with single viral particles in enclosed vesicular compartments or surface-localized virus particles and that large fluorescent signals correlated with membranous Gag-containing structures with unknown pathological function. CLEM imaging revealed distinct pools of newly deposited viral proteins within endocytic and nonendocytic compartments in VS target T cells. IMPORTANCE: This study directly correlates individual virus-associated objects observed in light microscopy with ultrastructural features seen by electron microscopy in the HIV-1 virological synapse. This approach elucidates which infection-associated ultrastructural features represent bona fide HIV protein complexes. We define the morphology of some HIV cell-to-cell transfer intermediates as true endocytic compartments and resolve unique synapse-associated viral structures created by transfer across virological synapses.

In Vivo HIV-1 Cell-to-Cell Transmission Promotes Multicopy Micro-compartmentalized Infection.

HIV-1 infection is enhanced by adhesive structures that form between infected and uninfected T cells called virological synapses (VSs). This mode of transmission results in the frequent co-transmission of multiple copies of HIV-1 across the VS, which can reduce sensitivity to antiretroviral drugs. Studying HIV-1 infection of humanized mice, we measured the frequency of co-transmission and the spatiotemporal organization of infected cells as indicators of cell-to-cell transmission in vivo. When inoculating mice with cells co-infected with two viral genotypes, we observed high levels of co-transmission to target cells. Additionally, micro-anatomical clustering of viral genotypes within lymphoid tissue indicates that viral spread is driven by local processes and not a diffuse viral cloud. Intravital splenic imaging reveals that anchored HIV-infected cells induce arrest of interacting, uninfected CD4(+) T cells to form Env-dependent cell-cell conjugates. These findings suggest that HIV-1 spread between immune cells can be anatomically localized into infectious clusters.

Energy sources for gynecologic laparoscopic surgery: a review of the literature.

IMPORTANCE: A range of energy sources are used in gynecologic laparoscopy. These energy sources include monopolar electrosurgery, bipolar electrosurgery (including "advanced bipolar" devices that incorporate tissue feedback monitoring), and various types of laser and ultrasonic technologies. Gynecologists using these tools should be aware of the potential benefits and potential dangers of these instruments. OBJECTIVE: This review provides an overview of the biophysics of these energy sources, their tissue effects, and the complications that may arise. It aims to highlight any potential advantages or disadvantages of various energy sources, as reported by clinical and laboratory studies. EVIDENCE ACQUISITION: Literature relating to energy sources used in gynecologic laparoscopy was reviewed. RESULTS: While laboratory-based studies have reported differences between various energy sources, these differences may not be clinically significant. The choice of instrumentation may depend on the nature of the surgical task being performed, but other factors, such as the surgeon's training/experience, cost, and industry marketing, may also influence the decision. CONCLUSIONS: TAn awareness of the pros and cons of each energy modality and their relative efficacy profiles is paramount. RELEVANCE: It is important that surgeons have an understanding of the biophysics of these technologies in order to understand their limitations and potential dangers and to utilize the most appropriate energy source(s) in the appropriate clinical setting, in order to both minimize the risk of inadvertent injuries during gynecologic laparoscopy and to maximize cost-efficient delivery of health care.

A study of effects of peptide fragments of bovine and human lactoferrins on activities of three key HIV-1 enzymes.

The intent of this study was to examine human and bovine lactoferrin fragments including lactoferrin (1-11), lactoferricin and lactoferrampin, all of which did not demonstrate hemolytic activity toward rabbit erythrocytes at 1 mM concentration, for possible inhibitory effects on the activities of HIV-1 reverse transcriptase, protease and integrase. The data showed that human lactoferricin was the most potent in inhibiting HIV-1 reverse transcriptase (IC50 =2 µM). Bovine lactoferricin (IC50 = 10 µM) and bovine lactoferrampin (IC50 = 150 µM) were less potent. Human lactoferrampin and human and bovine lactoferrin (1-11) at 1 mM concentration did not exhibit any inhibitory effect on HIV-1 reverse transcriptase. All peptides showed only a slight inhibitory effect (from slightly below 2% to 6% inhibition) on HIV-1 protease. Human lactoferrampin and bovine lactoferrampin showed obvious inhibitory effect on HIV-1 integrase at 37 µM and 18.5 µM, respectively. The HIV-1 integrase inhibitory activity of human lactoferrampin and bovine lactoferrampin was dose-dependent. The other peptides were devoid of HIV-1 integrase inhibitory activity. Thus, it is concluded that some lactoferrin fragments exert an inhibitory action on HIV-1 reverse transcriptase and HIV-1 integrase.

Urinary retention following laparoscopic gynaecological surgery with or without 4% icodextrin anti-adhesion solution.

BACKGROUND: Urinary retention is a recognised complication of laparoscopic surgery. Previous work showed an association with 4% icodextrin solution and urinary retention. AIMS: To determine the incidence of urinary retention following laparoscopic gynaecological surgery with or without the use of 4% icodextrin. METHODS: A prospective observational study of 147 women undergoing laparoscopic gynaecological surgery for benign pathology. Women had their planned laparoscopic procedure and either received icodextrin solution or nothing as determined by their treating surgeon at the time of the operation. RESULTS: From May 2011 to February 2012, 147 women were approached to participate in the study; of whom, 124 women were included: 62 received icodextrin and 62 did not. The women in the non-icodextrin group were significantly older (P = 0.007) and had a higher BMI (P = 0.03) than those in the icodextrin group. Following surgery, 27/124 (21.8%) women had post-operative urinary retention. Icodextrin was associated with significantly more urinary retention (P = 0.017), but did not extend hospital admission significantly (P = 0.14). The administration of icodextrin was associated with resection of moderate- or severe-stage endometriosis involving multiple surgical sites, whereas women in the non-icodextrin group were more likely to be having a hysterectomy. CONCLUSIONS: In this non-randomised study, there were significantly more women with post-operative urinary retention when icodextrin was used; however, this did not contribute to an extended hospital admission. While there may be confounding factors, women receiving icodextrin should be warned of the possibility of urinary retention post-operatively, but that this is unlikely to affect their stay in hospital.

Laparoscopic vessel sealing technologies.

Laparoscopic vessel sealing devices have revolutionized modern laparoscopy. These devices fall into 2 major categories: advanced bipolar and ultrasonic instruments. The range of tissue effects available with these technologies is more limited than with conventional monopolar electrosurgery; however, both advanced bipolar and ultrasonic devices efficiently seal vessels (≤7-mm and ≤5-mm diameter, respectively), and most also have built-in tissue transection capabilities. These technologies have been the subject of a range of comparative studies on their relative advantages and disadvantages, and, to date, neither advanced bipolar or ultrasonic devices has been proven to be superior.

Comparative studies of energy sources in gynecologic laparoscopy.

Energy sources incorporating "vessel sealing" capabilities are being increasingly used in gynecologic laparoscopic surgery although conventional monopolar and bipolar electrosurgery remain popular. The preference for one device over another is based on a combination of factors, including the surgeon's subjective experience, availability, and cost. Although comparative clinical studies and meta-analyses of laparoscopic energy sources have reported small but statistically significant differences in volumes of blood loss, the clinical significance of such small volumes is questionable. The overall usefulness of the various energy sources available will depend on a number of factors including vessel burst pressure and seal time, lateral thermal spread, and smoke production. Animal studies and laboratory-based trials are useful in providing a controlled environment to investigate such parameters. At present, there is insufficient evidence to support the use of one energy source over another.

A comparative study assessing the efficacy and acceptability of anorectal swabs for antenatal GBS screening.

OBJECTIVES: To assess women's perception of pain and acceptability of low vaginal swab (LVS) and anorectal swab (ARS) for antenatal screening for Group B Streptococcus (GBS), and to compare the detection rate between these tests. METHODS: Separate LVS and ARS were collected at the 36-week antenatal visit, either by the patient herself or by her clinician. Acceptability and pain were evaluated on a Likert scale using a standardised questionnaire. RESULTS: A total of 278 women were recruited, with a median gestation of 36.3 weeks (IQR 36-37). Of these women, 96% undertook specimen self-collection. The overall prevalence of colonisation was 64/278 (23%); 52 women had positive LVS results (18.7%), and an additional 12 (5.5%; 95% CI 2.5-8.5) were negative on LVS but positive on ARS. Most women rated LVS (99%) and ARS (92%) to be either 'pain-free' or causing 'mild discomfort', and found the LVS (90%) and ARS (84%) to be either 'totally acceptable' or 'somewhat acceptable'. CONCLUSIONS: The addition of an ARS resulted in an enhanced GBS positive rate, and most women found the test acceptable.

Laparoscopic subtotal hysterectomy: evidence and techniques.

Laparoscopic subtotal/supracervical hysterectomy (LSH) is a surgical option when hysterectomy is indicated. Proponents of LSH suggest possible advantages including reduced recovery time, decreased risk of pelvic organ prolapse, and decreased risk of organ damage, in particular to the urinary tract. Opponents of LSH have suggested that the future risk of cervical malignancy, the possibility of ongoing cyclical bleeding, limited morbidity due to total laparoscopic hysterectomy, and similar clinical outcomes render this approach unnecessary. One study compared LSH with laparoscopically assisted vaginal hysterectomy in a randomized controlled trial that reported psychologic and sexual outcomes; however, no clinical data were published. The present review outlines techniques for subtotal hysterectomy and critically appraises the available evidence for outcomes including operative data, short- and long-term complications, and functional outcomes.

Pharmacokinetics of eribulin mesylate in patients with solid tumours receiving repeated oral rifampicin.

AIM: Eribulin mesylate is a non-taxane microtubule dynamics inhibitor that was recently approved for treatment of metastatic breast cancer. The aim of this study was to determine the effect of rifampicin, a CYP3A4 inducer, on the plasma pharmacokinetics of eribulin in patients with solid tumours. METHODS: An open-label, non-randomized phase I study was carried out. Patients received intravenous 1.4 mg m(-2) eribulin mesylate on days 1 and 15 and oral rifampicin 600 mg on days 9 to 20 of a 28 day cycle. Pharmacokinetic sampling for determination of eribulin plasma concentrations was performed up to 144 h following administration. AUC(0,∞) and C(max) for eribulin exposure without or with co-administration of rifampicin were subjected to an analysis of variance (anova) and corresponding 90% confidence intervals (CI) were calculated. Subsequently, patients were allowed to continue eribulin mesylate treatment with 1.4 mg m(-2) eribulin mesylate on days 1 and 8 of a 21 day cycle. Also the adverse event profile and anti-tumour activity were assessed. RESULTS: Fourteen patients were included and 11 patients were evaluable for pharmacokinetic analysis. Co-administration of rifampicin had no effect on single dose exposure to eribulin (geometric least square means ratio: AUC(0,∞) = 1.10, 90% CI 0.91, 1.34 and C(max) = 0.97, 90% 0.81, 1.17). The most common treatment-related grade ≥3 adverse events were grade 3 neutropenia (4/14, 29%), leucopenia and fatigue (both 3/14, 21%). CONCLUSIONS: These results indicate that eribulin mesylate may be safely co-administered with compounds that are CYP3A4 inducers.

A phase I, open-label, single-arm study for QT assessment of eribulin mesylate in patients with advanced solid tumors.

BACKGROUND: Several cancer therapies can prolong cardiac repolarization. This study assessed the potential of eribulin to affect cardiac repolarization in patients with advanced solid tumors. METHODS: In this Phase I, open-label, single-arm study, patients received eribulin mesylate (1.4 mg/m(2); Days 1 and 8 of a 21-day cycle). The primary objective was to assess the effect of eribulin on the QTcF pre- and post-infusion; QTcF and QTcNi were compared for ability to remove heart-rate dependence of the QT interval. Relationship between concentration of eribulin and ΔQTc was explored using linear mixed-effects analysis. Secondary objectives explored pharmacokinetics, safety, and tolerability. RESULTS: Twenty-six patients were enrolled. QTcNi was more effective than QTcF in correcting for heart-rate dependency of the QT interval. On Day 1, mean ΔQTcNi were ~0 at all timepoints. An apparent time-dependent increase in ΔQTc was observed: on Day 8, changes from baseline were larger and more variable, without clear relation to plasma levels of eribulin. Day 8 predose ΔQTcNi was 5 ms, post-infusion mean values ranged from 2 to 9 ms (largest mean ΔQTcNi at 6 h). No new or unexpected toxicities were reported. CONCLUSION: Eribulin demonstrated an acceptable safety profile and a minor prolongation of QTc not expected to be of clinical concern in oncology patients.