Effectiveness of interventions on sedentary behaviors in office workers: a systematic review and meta-analysis.

OBJECTIVES: Various interventions have sought to break sedentariness among office workers, but their pooled effect on sitting time reduction remains unknown. Also, it is essential to compare the effectiveness of different intervention types. STUDY DESIGN: Systematic review and meta-analysis. METHODS: A literature search was conducted in the PubMed, EMBASE, Scopus, Web of Science, MEDLINE (via EBSCO), PsycINFO, and Cochrane Library databases from inception to May 2, 2023. Two independent reviewers screened eligibility, extracted data, and assessed the risk of bias using the Cochrane risk of bias tool 2.0. Randomized controlled trials aiming to reduce sitting at work were included. The primary outcome was sitting time at work per day. The secondary outcomes included cardiometabolic risk factors, psychological well-being, and work engagement. A random effects model was performed to synthesize continuous data as mean differences with 95% confidence intervals (95% CIs). RESULTS: Twenty-four studies with 3169 participants were included. All intervention types in combination significantly reduced workplace sitting by 38 min per workday (95% CI: -47.32 to -28.72; P < 0.001; I2 = 49.78%). Interventions using environmental support (ES), motivational strategies (MS), or multiple components (multi) had all shown a significant reduction in work-time sedentary behavior (SB) relative to control groups. Regarding secondary outcomes, no significant effects were observed in physical or psychological outcomes besides high-density lipoprotein. CONCLUSIONS: Findings suggest that SB reduction interventions are generally effective for reducing workplace sitting. Multi interventions with both ES and MS are recommended for future clinical applications. Future studies should aim not only to reduce SB but also to attain the benefits of SB reduction interventions on physical and psychological well-being.

Evaluating the Hounsfield unit assignment and dose differences between CT-based standard and deep learning-based synthetic CT images for MRI-only radiation therapy of the head and neck.

BACKGROUND: Magnetic resonance image only (MRI-only) simulation for head and neck (H&N) radiotherapy (RT) could allow for single-image modality planning with excellent soft tissue contrast. In the MRI-only simulation workflow, synthetic computed tomography (sCT) is generated from MRI to provide electron density information for dose calculation. Bone/air regions produce little MRI signal which could lead to electron density misclassification in sCT. Establishing the dosimetric impact of this error could inform quality assurance (QA) procedures using MRI-only RT planning or compensatory methods for accurate dosimetric calculation. PURPOSE: The aim of this study was to investigate if Hounsfield unit (HU) voxel misassignments from sCT images result in dosimetric errors in clinical treatment plans. METHODS: Fourteen H&N cancer patients undergoing same-day CT and 3T MRI simulation were retrospectively identified. MRI was deformed to the CT using multimodal deformable image registration. sCTs were generated from T1w DIXON MRIs using a commercially available deep learning-based generator (MRIplanner, Spectronic Medical AB, Helsingborg, Sweden). Tissue voxel assignment was quantified by creating a CT-derived HU threshold contour. CT/sCT HU differences for anatomical/target contours and tissue classification regions including air (<250 HU), adipose tissue (-250 HU to -51 HU), soft tissue (-50 HU to 199 HU), spongy (200 HU to 499 HU) and cortical bone (>500 HU) were quantified. t-test was used to determine if sCT/CT HU differences were significant. The frequency of structures that had a HU difference > 80 HU (the CT window-width setting for intra-cranial structures) was computed to establish structure classification accuracy. Clinical intensity modulated radiation therapy (IMRT) treatment plans created on CT were retrospectively recalculated on sCT images and compared using the gamma metric. RESULTS: The mean ratio of sCT HUs relative to CT for air, adipose tissue, soft tissue, spongy and cortical bone were 1.7 ± 0.3, 1.1 ± 0.1, 1.0 ± 0.1, 0.9 ± 0.1 and 0.8 ± 0.1 (value of 1 indicates perfect agreement). T-tests (significance set at t = 0.05) identified differences in HU values for air, spongy and cortical bone in sCT images compared to CT. The structures with sCT/CT HU differences > 80 HU of note were the left and right (L/R) cochlea and mandible (>79% of the tested cohort), the oral cavity (for 57% of the tested cohort), the epiglottis (for 43% of the tested cohort) and the L/R TM joints (occurring > 29% of the cohort). In the case of the cochlea and TM joints, these structures contain dense bone/air interfaces. In the case of the oral cavity and mandible, these structures suffer the additional challenge of being positionally altered in CT versus MRI simulation (due to a non-MR safe immobilizing bite block requiring absence of bite block in MR). Finally, the epiglottis HU assignment suffers from its small size and unstable positionality. Plans recalculated on sCT yielded global/local gamma pass rates of 95.5% ± 2% (3 mm, 3%) and 92.7% ± 2.1% (2 mm, 2%). The largest mean differences in D95, Dmean , D50 dose volume histogram (DVH) metrics for organ-at-risk (OAR) and planning tumor volumes (PTVs) were 2.3% ± 3.0% and 0.7% ± 1.9% respectively. CONCLUSIONS: In this cohort, HU differences of CT and sCT were observed but did not translate into a reduction in gamma pass rates or differences in average PTV/OAR dose metrics greater than 3%. For sites such as the H&N where there are many tissue interfaces we did not observe large scale dose deviations but further studies using larger retrospective cohorts are merited to establish the variation in sCT dosimetric accuracy which could help to inform QA limits on clinical sCT usage.

Cadaver Study on Transoral Thyroid Chondrolaryngoplasty and Transoral Sistrunk Operation, Possibility from Transoral Thyroidectomy.

OBJECTIVE: Transoral approaches in surgery are gaining global popularity. Transoral endoscopic and robotic thyroidectomies are well established due to the benefit of being truly scarless. Thyroid chondrolaryngoplasty reduces protrusion of the thyroid notch in transgender patients. The Sistrunk operation involves removal of the thyroglossal cyst and the central portion of the hyoid bone. In this cadaveric study, we developed a transoral thyroidectomy approach and assessed the feasibility of applying this technique to thyroid chondrolaryngoplasty and Sistrunk operation with the proper usage of a special endoscopic burr. METHODS: We performed surgery using the transoral vestibular approach with 13 fresh-frozen human cadavers. Unlike transoral thyroid surgery, which requires high-resolution detailed anatomical view, this technique uses a 5-mm 30-degree endoscope with a 5-mm central port. A smaller central port can reduce the risk of mental nerve paresthesia. A special endoscopic burr for functional endoscopic sinus surgery is used to thin the thyroid notch cartilage and cut the central portion of the hyoid bone. RESULTS: We successfully performed transoral thyroid chondrolaryngoplasty and transoral Sistrunk operation in 13 cadavers. CONCLUSION: Transoral chondrolaryngoplasty and transoral Sistrunk operation are feasible for transgender or thyroglossal cyst patients. It offers the additional benefit of being a scarless surgery and could play a promising role in minimally invasive thyroid surgeries. Proper use of an endoscopic drilling burr to thin thyroid notch cartilage and cutting the central portion of the hyoid bone can make transoral thyroid chondrolaryngoplasty and transoral Sistrunk operation safe and feasible .

A novel mechanism of enhanced transcription activity and fidelity for influenza A viral RNA-dependent RNA polymerase.

During RNA elongation, the influenza A viral (IAV) RNA-dependent RNA polymerase (RdRp) residues in the active site interact with the triphosphate moiety of nucleoside triphosphate (NTP) for catalysis. The molecular mechanisms by which they control the rate and fidelity of NTP incorporation remain elusive. Here, we demonstrated through enzymology, virology and computational approaches that the R239 and K235 in the PB1 subunit of RdRp are critical to controlling the activity and fidelity of transcription. Contrary to common beliefs that high-fidelity RdRp variants exert a slower incorporation rate, we discovered a first-of-its-kind, single lysine-to-arginine mutation on K235 exhibited enhanced fidelity and activity compared with wild-type. In particular, we employed a single-turnover NTP incorporation assay for the first time on IAV RdRp to show that K235R mutant RdRp possessed a 1.9-fold increase in the transcription activity of the cognate NTP and a 4.6-fold increase in fidelity compared to wild-type. Our all-atom molecular dynamics simulations further elucidated that the higher activity is attributed to the shorter distance between K235R and the triphosphate moiety of NTP compared with wild-type. These results provide novel insights into NTP incorporation and fidelity control mechanisms, which lay the foundation for the rational design of IAV vaccine and antiviral targets.

Activation of the viral sensor oligoadenylate synthetase 2 (Oas2) prevents pregnancy-driven mammary cancer metastases.

BACKGROUND: The interferon response can influence the primary and metastatic activity of breast cancers and can interact with checkpoint immunotherapy to modulate its effects. Using N-ethyl-N-nitrosourea mutagenesis, we found a mouse with an activating mutation in oligoadenylate synthetase 2 (Oas2), a sensor of viral double stranded RNA, that resulted in an interferon response and prevented lactation in otherwise healthy mice. METHODS: To determine if sole activation of Oas2 could alter the course of mammary cancer, we combined the Oas2 mutation with the MMTV-PyMT oncogene model of breast cancer and examined disease progression and the effects of checkpoint immunotherapy using Kaplan-Meier survival analysis with immunohistochemistry and flow cytometry. RESULTS: Oas2 mutation prevented pregnancy from increasing metastases to lung. Checkpoint immunotherapy with antibodies against programmed death-ligand 1 was more effective when the Oas2 mutation was present. CONCLUSIONS: These data establish OAS2 as a therapeutic target for agents designed to reduce metastases and increase the effectiveness of checkpoint immunotherapy.

Increased Stability of SARS-CoV-2 Omicron Variant over Ancestral Strain.

As of April 2022, the Omicron BA.1 variant of concern of SARS-CoV-2 was spreading quickly around the world and outcompeting other circulating strains. We examined its stability on various surfaces and found that this Omicron variant is more stable than its ancestral strain on smooth and porous surfaces.

Poisson item count techniques with noncompliance.

The Poisson item count technique (PICT) is a survey method that was recently developed to elicit respondents' truthful answers to sensitive questions. It simplifies the well-known item count technique (ICT) by replacing a list of independent innocuous questions in known proportions with a single innocuous counting question. However, ICT and PICT both rely on the strong "no design effect assumption" (ie, respondents give the same answers to the innocuous items regardless of the absence or presence of the sensitive item in the list) and "no liar" (ie, all respondents give truthful answers) assumptions. To address the problem of self-protective behavior and provide more reliable analyses, we introduced a noncompliance parameter into the existing PICT. Based on the survey design of PICT, we considered more practical model assumptions and developed the corresponding statistical inferences. Simulation studies were conducted to evaluate the performance of our method. Finally, a real example of automobile insurance fraud was used to demonstrate our method.

Protective Effects of Melatonin on Neurogenesis Impairment in Neurological Disorders and Its Relevant Molecular Mechanisms.

Neurogenesis is the process by which functional new neurons are generated from the neural stem cells (NSCs) or neural progenitor cells (NPCs). Increasing lines of evidence show that neurogenesis impairment is involved in different neurological illnesses, including mood disorders, neurogenerative diseases, and central nervous system (CNS) injuries. Since reversing neurogenesis impairment was found to improve neurological outcomes in the pathological conditions, it is speculated that modulating neurogenesis is a potential therapeutic strategy for neurological diseases. Among different modulators of neurogenesis, melatonin is a particularly interesting one. In traditional understanding, melatonin controls the circadian rhythm and sleep-wake cycle, although it is not directly involved in the proliferation and survival of neurons. In the last decade, it was reported that melatonin plays an important role in the regulation of neurogenesis, and thus it may be a potential treatment for neurogenesis-related disorders. The present review aims to summarize and discuss the recent findings regarding the protective effects of melatonin on the neurogenesis impairment in different neurological conditions. We also address the molecular mechanisms involved in the actions of melatonin in neurogenesis modulation.

"I'm not an addict": A thematic analysis of addiction experiences among Chinese female methamphetamine users. / «No soy una adicta¼: Un análisis temático de las experiencias de adicción entre mujeres chinas consumidoras de metanfetaminas.

Methamphetamine (meth) use has become a serious health epidemic in China, and the number of female meth users has risen substantially in the previous decade. However, until recently, patterns of meth addiction among Chinese women were rarely studied. To fill the void, this study implemented a thematic analysis approach to investigate Chinese female meth users' addiction experiences based on 49 semi-structured interview transcripts. The findings reveal that Chinese female meth users generally believe that meth is not physically addictive, but can cause their psychological dependence. Meth use leads to users' psychological enjoyment, and in addition to this, it has other functions. For example, some people use meth as a necessity to relieve stress, keep fit, alleviate pain, cure diseases, and deal with alcoholism. The findings also demonstrate that meth use is indispensable in particular social networks based on participants' socioeconomic backgrounds, especially those from low socioeconomic backgrounds. By understanding their experiences on meth addiction, both formal educational programs and social media exposure are suggested to provide female meth users, especially those situated in high-risk social networks, with adequate and up-to-date meth knowledge. Educational programs are also needed during treatment. Targeted interventions and social support programs are further recommended to help female meth users avoid severe health issues due to meth consumption.

El consumo de metanfetaminas (meta) se ha convertido en una epidemia grave de salud en China, y el número de consumidoras de meta ha aumentado de manera importante en la última década. Sin embargo, rara vez se había estudiado los patrones de adicción a la meta entre mujeres chinas hasta hace poco. Para llenar el vacío, este estudio realizó un análisis temático para investigar las experiencias de adicción de mujeres chinas consumidoras de meta, en base a las transcripciones de 49 entrevistas semi-estructuradas. Estos hallazgos revelan que las chinas consumidoras de meta piensan, en general, que la meta no es físicamente adictiva­ a pesar de que pueda provocarles dependencia psicológica. El consumo de meta les genera un disfrute psicológico, además de cumplir otras funciones. Por ejemplo, algunas personas la necesitan para aliviar el estrés, mantenerse en forma, disminuir el dolor, curar enfermedades y afrontar el alcoholismo. Los hallazgos también muestran que el consumo de meta es indispensable en algunas clases sociales específicas, según el nivel socioeconómico de las consumidoras, en particular entre aquellas de niveles socioeconómicos bajos. Mediante la comprensión de sus experiencias en torno a la adicción a la meta, se recomiendan programas educativos formales como la exposición a redes sociales para aportar a las mujeres consumidoras de meta ­en particular las de clases sociales de alto riesgo­ conocimientos actualizados y adecuados sobre la sustancia. Los tratamientos también requieren programas educativos. Es más, se recomiendan intervenciones dirigidas y programas de apoyo social para ayudar a las consumidoras de meta a evitar problemas graves de salud debido a su consumo.

Impact of antibiotic stewardship programmes in Asia: a systematic review and meta-analysis.

Background: The use of antibiotic stewardship programmes (ASPs) is increasing in Asia, but their effectiveness in reducing antibiotic consumption and their impact on clinical outcomes is not known. Objectives: To determine the impact of ASPs conducted in Asia on the consumption of antibiotics and on patients' clinical outcomes. Methods: We systematically searched the Embase and Medline (PubMed) databases for studies that compared antibiotic consumption or clinical outcomes of patients in an Asian hospital or clinic with an ASP (intervention) with those in a similar setting without an ASP (control). Meta-analyses of all-cause mortality and hospital-acquired infection (HAI) were performed using random-effects models. Results: The search identified 77 studies of which 22 and 19 reported antibiotic usage and cost, respectively. Among these, 20 (91%) studies reported reduced antibiotic usage and 19 (100%) reported cost savings in the intervention group. Duration of antibiotic therapy was reduced in six of seven studies in association with an ASP. Rates of all-cause mortality and HAI were not significantly different between the intervention and control groups. However, mortality rates were significantly improved by ASPs using drug monitoring, while HAI rates were also improved by ASPs that included infection control or hand hygiene programmes. Conclusions: In Asia, ASPs reduce antibiotic consumption in hospital and clinic settings and do not worsen clinical outcomes. The findings strongly support the broad implementation of antimicrobial stewardship interventions in hospital and clinic settings in Asia.

Management of behavioural and psychological symptoms of dementia by an aroma-massage with acupressure treatment protocol: A randomised clinical trial.

AIMS AND OBJECTIVES: This study evaluates the clinical effectiveness of a multicomponent aroma-massage with an acupressure treatment protocol and compared it to cognitive training for the management of behavioural and psychological symptoms of dementia. BACKGROUND: Pharmacological interventions have been unsatisfactory in managing behavioural and psychological symptoms of dementia; thus, complementary and alternative medicine has been extensively researched to identify an adjunct safe and cost-effective intervention. DESIGN: This randomised clinical trial utilised a three-arm parallel group design. Cognitive training was used as a conventional intervention to manage behavioural and psychological symptoms of dementia, whereas exercise was considered "treatment as usual" in this study; both were used as comparisons with the experimental protocol. There were three treatment groups: Group 1: aroma-massage with acupressure + exercise, Group 2: cognitive training + exercise and Group 3: aroma-massage with acupressure + cognitive training. METHOD: Sixty older adults were recruited and randomly assigned to the three groups (20 each). Using the 29-item Chinese Version of the Cohen-Mansfield Agitation Inventory, Neuropsychiatric Inventory, Mini-mental State Examination and Barthel Index-20, the outcome measures were assessed at preintervention, postintervention and the 3-month follow-up to assess behaviour, Activities of Daily Living, cognition, and behavioural and psychological symptoms of dementia severity and distress. Multiple comparisons performed through repeated measures were analysed to detect between-group differences and within-subject differences, as well as the interaction effects between groups and times. RESULTS: The Group 1 and 3 participants showed a significant reduction in the severity and distress caused by behavioural and psychological symptoms of dementia, whereas Group 2 did not demonstrate similar effects. CONCLUSIONS: This clinical study suggests that aroma-massage with acupressure is as effective as cognitive training and can enhance cognitive training in reducing the severity and distress of behavioural and psychological symptoms of dementia. RELEVANCE TO CLINICAL PRACTICE: Aroma-massage with acupressure may serve as an adjunct therapy to reduce behavioural and psychological symptoms of dementia. This therapy is safe, cost-effective and can be implemented by caregivers and family members who are not professionally trained.

Use of indocyanine green angiography in microsurgical subinguinal varicocelectomy - lessons learned from our initial experience.

Microsurgical subinguinal varicocelectomy (MSV) is generally considered the gold standard nowadays in view of the lower risk of complications and recurrence. To achieve complete ligation of veins while preserving testicular artery (TA) during the procedure remains challenging despite the application of high power optical magnification and micro-Doppler ultrasonography. The use of intraoperative indocyanine green angiography (ICGA) with infrared fluorescence operative micro-scope in MSV potentially lowers the incidence of TA injury and shortens the learning curve of nov-ice surgeons. We present our initial experience in the application of the technique in nine patients and explore the potential of the new adjunct.

Integrated Supported Employment for People With Schizophrenia in Mainland China: A Randomized Controlled Trial.

OBJECTIVE: In this randomized controlled trial, we investigated the effectiveness of integrated supported employment (ISE) compared with individual placement and support (IPS) and traditional vocational rehabilitation (TVR) for people with schizophrenia in mainland China. METHOD: One hundred and sixty-two participants with schizophrenia were randomly assigned to ISE (n = 54), IPS (n = 54), or TVR (n = 54). Blinded assessments of employment status, job tenure, and psychological outcomes were conducted at admission; completion of the 3-mo program; and follow-up at 7, 11, and 15 mo. RESULTS: Significantly higher employment rate and longer job tenure were found in the ISE group (63.0%, 29.56 wk) compared with the IPS group (50.0%, 25.47 wk) and TVR group (33.3%, 9.91 wk). The ISE group also attained the most positive psychological outcomes. CONCLUSION: Work-related social skills training embedded in ISE with generalization strategies can enhance vocational and nonvocational outcomes for people with schizophrenia in mainland China.

Solution-processable organic-inorganic hybrid hole injection layer for high efficiency phosphorescent organic light-emitting diodes.

The presence of a solution-processed hybrid PEDOT: PSS-MoO3-based hole injection layer (HIL) promotes a good interfacial contact between the indium tin oxide anode and hole-transporting layer for efficient operation of organic light-emitting diodes (OLEDs). This work reveals that the use of the hybrid HIL benefits the performance of phosphorescent OLEDs in two ways: (1) to assist in efficient hole injection, thereby improving power efficiency of OLEDs, and (2) to improve electron-hole current balance and suppression of interfacial defects at the organic/anode interface. The combined effects result in the power efficiency of 89.2 lm/W and external quantum efficiency of 23.9% for phosphorescent green OLEDs. The solution-processed hybrid PEDOT: PSS-MoO3-based HIL is beneficial for application in solution-processed organic electronic devices.

Technique for office-based, ultrasonography-guided percutaneous biopsy of renal cortical neoplasms using a novel transducer for facilitated ultrasound targeting.

OBJECTIVES: To help clarify which small renal cortical neoplasms (RCNs) require surgery by using office-based, ultrasonography-guided percutaneous renal biopsy. PATIENTS AND METHODS: Biopsies were performed using facilitated ultrasound targeting (FUT) technology, which incorporates a needle guide and onscreen beam-steered technology to permit highly precise needle deployment. Patient and tumour characteristics, procedure time, complications and biopsy efficacy were documented. Wong-Baker pain levels were obtained before, during and 1 h after the procedure. RESULTS: Seven patients underwent biopsy, six for RCNs and one for medical renal disease. The mean (range) patient age was 68.5 (54-79) years, and the mean (range) tumour diameter was 2.55 (2.0-2.9) cm. Mean pain levels before, during and 1 h after the procedure were 0, 1.6 and 0.5, respectively. There were no intra- or post-procedural complications. Biopsy results were diagnostic in five of the six RCN cases and in the single case of medical renal disease. CONCLUSIONS: Our preliminary experience shows that office-based percutaneous renal biopsy using a novel transducer for FUT is safe and effective. An international multicentre study is planned to confirm these preliminary results.

Association Between Caregiver Stress and Behavioral Problems in the Children of Incarcerated Fathers in Hong Kong.

Objectives Caregivers of children with incarcerated parents have received little attention in the literature, though they face unique incarceration-related challenges. General caregiver research has highlighted associations between caregiver distress and children's behavioral problems, even implying that the depressive tendencies of caregivers can be 'transmitted'. The current study investigated the applicability of this notion to caregivers responsible for children of incarcerated fathers. Methods Fifty-four female caregivers of children with incarcerated parents were recruited via collaboration with a non-governmental organization. Their levels of stress and depression were measured using questionnaires, as were the behavioral problems of children under their care. The relationships between the variables were examined. Results The results firstly suggest that these caregivers are vulnerable to psychological distress, with around 57 % of them suffering from borderline to severe depression. Obtained socio-demographic characteristics were not found to have any bearing on the psychosocial functioning of caregivers or children-rather, all psychosocial variables were interlinked, and further analyses revealed that the depression of caregivers mediated the relationship between their perceived stress and internalizing/externalizing behavioral problems of the child (ß = .628 and ß = .468 respectively), implicating depression as a mechanism via which adversity can be transferred from a caregiver to a child. Conclusions Increasing the focus on a caregiver's mental health may be an efficacious strategy in research and practice, perhaps by providing more support for caregivers and implementing joint caregiver-child interventions to more holistically alleviate problems in families affected by parental incarceration. Limitations of the current study and further recommendations are also discussed.

Emission behavior of dual-side emissive transparent white organic light-emitting diodes.

White organic light-emitting diodes (WOLEDs) resemble light more naturally, with emission spectrum that is comfortable to the human eye. The transparent WOLEDs can be almost invisible by day and can emit a pleasant diffused light at night, allowing the surface light source to shine in both directions, an exciting new lighting technology that could bring new device concepts. However, undesirable angular-dependent emission in transparent WOLEDs is often observed, due to the microcavity effect. In this work, the emission behavior of dual-side emissive transparent WOLEDs was studied experimentally and theoretically. It is found that avoidance of the overlap between the peak wavelengths of the emitters and the resonant wavelength of the organic microcavity moderates the angular-dependent electroluminescence emission behavior, thereby improving the color stability of the transparent white WOLEDs over a broad range of the viewing angle.

Cancer cell-derived lymphotoxin mediates reciprocal tumour-stromal interactions in human ovarian cancer by inducing CXCL11 in fibroblasts.

We have investigated the role of cytokine lymphotoxin in tumour-stromal interactions in human ovarian cancer. We found that lymphotoxin overexpression is commonly shared by the cancer cells of various ovarian cancer subtypes, and lymphotoxin-beta receptor (LTBR) is expressed ubiquitously in both the cancer cells and cancer-associated fibroblasts (CAFs). In monoculture, we showed that ovarian cancer cells are not the major lymphotoxin-responsive cells. On the other hand, our co-culture studies demonstrated that the cancer cell-derived lymphotoxin induces chemokine expression in stromal fibroblasts through LTBR-NF-κB signalling. Amongst the chemokines being produced, we found that fibroblast-secreted CXCL11 promotes proliferation and migration of ovarian cancer cells via the chemokine receptor CXCR3. CXCL11 is highly expressed in CAFs in ovarian cancer biopsies, while CXCR3 is found in malignant cells in primary ovarian tumours. Additionally, the overexpression of CXCR3 is significantly associated with the tumour grade and lymph node metastasis of ovarian cancer, further supporting the role of CXCR3, which interacts with CXCL11, in promoting growth and metastasis of human ovarian cancer. Taken together, these results demonstrated that cancer-cell-derived lymphotoxin mediates reciprocal tumour-stromal interactions in human ovarian cancer by inducing CXCL11 in fibroblasts. Our findings suggest that lymphotoxin-LTBR and CXCL11-CXCR3 signalling represent therapeutic targets in ovarian cancer.

Cutting edge: Receptors for C3a and C5a modulate stability of alloantigen-reactive induced regulatory T cells.

CD4(+)Foxp3(+) regulatory T cells (Treg) are critical regulators of immune homeostasis and self-tolerance. Whereas thymic-derived or natural Treg stably express Foxp3, adaptive or induced Treg (iTreg) generated from peripheral CD4 T cells are susceptible to inflammation-induced reversion to pathogenic effector T cells. Building upon our previous observations that T cell-expressed receptors for C3a (C3aR) and C5a (C5aR) drive Th1 maturation, we tested the impact of C3aR/C5aR signaling on induction and stability of alloreactive iTreg. We observed that genetic deficiency or pharmacological blockade of C3aR/C5aR signaling augments murine and human iTreg generation, stabilizes Foxp3 expression, resists iTreg conversion to IFN-γ/TNF-α-producing efffector T cells, and, as a consequence, limits the clinical expression of graft-versus-host disease. Taken together, the findings highlight the expansive role of complement as a crucial modulator of T cell alloimmunity and demonstrate proof-of-concept that targeting C3a/C3aR and C5a/C5aR interactions could facilitate iTreg-mediated tolerance to alloantigens in humans.

Left ventricular three-dimensional quadripolar lead acute clinical study: the LILAC study.

AIMS: This multicenter acute clinical study was designed to verify novel three-dimensional (3D) quadripolar lead designs that can achieve ≤2.5 V average pacing capture threshold (PCT) not only at the apex, but also at the base of the left ventricle with phrenic nerve stimulation (PNS) avoidance for cardiac resynchronization. METHODS: During the implant procedure, up to two different left ventricular investigational leads were introduced and tested in the same target coronary vein based on the coronary sinus venogram in a wedged and unwedged position. Adverse events were collected in 30 days following the procedure. RESULTS: Eighty-seven leads were tested in 50 patients. When the best performing spiral electrode was chosen from each lead testing, the average of the best PCT on spiral in a wedged position was similar to the unwedged position (1.7 ± 1.5 V vs 1.9 ± 1.5 V, P = ns) and was similar to the wedged tip electrode average PCT (1.7 ± 1.5 V vs 1.6 ± 1.6 V, P = ns). In the majority of patients (89-96%), pacing was achievable in a mid-basal ventricular location without PNS. CONCLUSIONS: This acute study demonstrated that a 3D quadripolar spiral lead design can achieve acceptable PCTs and avoid PNS without repositioning the lead at implant in the vast majority of patients. It also demonstrated that this lead design can achieve mid-basal ventricular stimulation with low PCT and good acute stability.