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Abstract The aim of this meta-analysis was to assess the association of general anesthesia (GA) exposure with the risk of POD in this patient population. Databases including Medline, EMBASE, Cochrane library, and Google Scholar were searched from inception to December 2022. Analysis of 17 studies published between 2015 and 2021 involving 10,678 individuals revealed an association of GA exposure with an elevated risk of POD [odd ratio (OR) = 1.846, 95% CI 1.329 to 2.563, p = 0.0003, I2 = 68.4%, 10,678 patients]. Subgroup analysis of the diagnostic methods also demonstrated a positive correlation between GA exposure and POD risk when validated methods were used for POD diagnosis (OR = 2.199, 95% CI 1.46 to 3.31, p = 0.0002). Meta-regression analyses showed no significant impact of age, male proportion, and sample size on the correlation between GA and the risk of POD. The reported overall incidence of POD from the included studies regardless of the type of anesthesia was between 0.8 and 27%. Our meta-analysis showed a pooled incidence of 10.3% (95% CI 7% to 15%). This meta-analysis suggested an association of general anesthesia with an elevated risk of postoperative delirium, implying the necessity of implementing appropriate prophylactic strategies against this complication when general anesthesia was used in this clinical setting.

BackgroundThe potential link between Prognostic Nutritional Index (PNI) and prognosis in patients with glioma remains uncertain. This meta-analysis was conducted to assess the clinical value of PNI in glioma patients by integrating all available evidence to enhance statistical power.MethodA systematic search of databases including Medline, EMBASE, Google Scholar, and Cochrane Library was conducted from inception to January 8, 2023 to retrieve all pertinent peer-reviewed articles. The primary outcome of the study was to examine the association between a high PNI value and overall survival, while secondary outcome included the relationship between a high PNI and progression-free survival.ResultsIn this meta-analysis, we included 13 retrospective studies published from 2016 to 2022, which analyzed a total of 2,712 patients. Across all studies, surgery was the primary treatment modality, with or without chemotherapy and radiotherapy as adjunct therapies. A high PNI was linked to improved overall survival (Hazard Ratio (HR) = 0.61, 95% CI: 0.52 to 0.72, p < 0.00001, I2 = 25%), and this finding remained consistent even after conducting sensitivity analysis. Subgroup analyses based on ethnicity (Asian vs. non-Asian), sample size (200), and source of hazard ratio (univariate vs. multivariate) yielded consistent outcomes. Furthermore, patients with a high PNI had better progression-free survival than those with a low PNI (HR=0.71, 95% CI: 0.58 to 0.88, p=0.001, I2 = 0%).ConclusionOur meta-analysis suggested that a high PNI was associated with better overall survival and progression-free survival in patients with glioma. These findings may have important implications in the treatment of patients with glioma. Additional studies on a larger scale are necessary to investigate if integrating the index into the treatment protocol leads to improved clinical outcomes in individuals with glioma.Systematic review registration[https://www.crd.york.ac.uk/prospero/], identifier [CRD42023389951].

Abstract Background The explanation of epidural analgesia by anesthesiologist would often begin after the parturient is admitted to the hospital. Because of labor pain, the decision of receiving epidural analgesia would often be made by the family members, instead of the parturient herself. We aimed to test whether earlier prenatal shared decision-making (SDM) interventions increase parturient’s comprehension and satisfaction of epidural labor analgesia, compared to conventional explanation after labor pain begun. Methods During the 28th week of gestation, we provided the SDM parturient health education as well as a leaflet with quick response codes. Scanning the code would link to education videoclips which explained what epidural analgesia is and its advantages and disadvantages. Original routine practice group parturients received explanation of analgesia after admission for delivery. To measure the satisfaction of labor pain service, the accessibility of information, and the communication with medical staff, we designed a questionnaire with reference to (1) Pregnancy and Maternity Care Patients’ Experiences Questionnaire (PreMaPEQ), (2) Preterm Birth Experience and Satisfaction Scale (P-BESS), and (3) Women’s Views of Birth Labor Satisfaction Questionnaire (WOMBLSQ). The questionnaire was amended after a pretest involving 30 parturients who had received epidural analgesia. Scree test analysis and exploratory factor analysis were performed; then, the questionnaire was revised again. A total of 200 valid questionnaires were collected—100 each from the original routine practice group and the SDM group. Results The SDM group reported significantly higher satisfaction with and understanding of epidural analgesia, and a significantly higher satisfaction with the information received, and the quality of pain relief. After SDM intervention, significant increasement of the average satisfaction scores in question “my epidural is effective” (9.10%; mean difference: 0.38; 95% confidence interval, 0.17 ~ 0.59; p

In recent years, we have witnessed rising trade protectionism with broad ranges of tariffs imposed on intermediate products. In this article, we develop an accounting framework to evaluate the sectoral impacts of the current U.S.-China trade war. We find that U.S. final demand and intermediate demand for goods produced by China decline significantly, with the largest losses occurring in the Electronic and ICT (information and communications technology) industry and the Electrical industry. We obtain sizable deadweight losses for the United States, particularly in the Electronic and ICT; Electrical; and Furniture industries. We also find that, with a leakage rate of 20 percent, total losses to U.S. consumers and importers are $3.3 billion, about 0.05 percent of gross U.S. output, whereas the full leakage losses are $10.7 billion, or 0.16 percent of gross U.S. output, which is twice as much as the annual welfare gains from the North America Free Trade Agreement. [ABSTRACT FROM AUTHOR]

Astrocytes are extensively infected with HIV-1 in vivo and play a significant role in the development of HIV-1-associated neurocognitive disorders. Despite their extensive infection, little is known about how astrocytes become infected, since they lack cell surface CD4 expression. In the present study, we investigated the fate of HIV-1 upon infection of astrocytes. Astrocytes were found to bind and harbor virus followed by biphasic decay, with HIV-1 detectable out to 72 hours. HIV-1 was observed to associate with CD81-lined vesicle structures. shRNA silencing of CD81 resulted in less cell-associated virus but no loss of co-localization between HIV-1 and CD81. Astrocytes supported trans-infection of HIV-1 to T-cells without de novo virus production, and the virus-containing compartment required 37°C to form, and was trypsin-resistant. The CD81 compartment observed herein, has been shown in other cell types to be a relatively protective compartment. Within astrocytes, this compartment may be actively involved in virus entry and/or spread. The ability of astrocytes to transfer virus, without de novo viral synthesis suggests they are capable of sequestering and protecting virus and thus, they could potentially facilitate viral dissemination in the CNS.

Histone deacetylase inhibitors (HDACi) can induce human immunodeficiency virus (HIV) transcription from the HIV long terminal repeat (LTR). However, ex vivo and in vivo responses to HDACi are variable and the activity of HDACi in cells other than T-cells have not been well characterised. Here, we developed a novel assay to determine the activity of HDACi on patient-derived HIV LTRs in different cell types. HIV LTRs from integrated virus were amplified using triple-nested Alu-PCR from total memory CD4+ T-cells (CD45RO+) isolated from HIV-infected patients prior to and following suppressive antiretroviral therapy. NL4-3 or patient-derived HIV LTRs were cloned into the chromatin forming episomal vector pCEP4, and the effect of HDACi investigated in the astrocyte and epithelial cell lines SVG and HeLa, respectively. There were no significant differences in the sequence of the HIV LTRs isolated from CD4+ T-cells prior to and after 18 months of combination antiretroviral therapy (cART). We found that in both cell lines, the HDACi panobinostat, trichostatin A, vorinostat and entinostat activated patient-derived HIV LTRs to similar levels seen with NL4-3 and all patient derived isolates had similar sensitivity to maximum HDACi stimulation. We observed a marked difference in the maximum fold induction of luciferase by HDACi in HeLa and SVG, suggesting that the effect of HDACi may be influenced by the cellular environment. Finally, we observed significant synergy in activation of the LTR with vorinostat and the viral protein Tat. Together, our results suggest that the LTR sequence of integrated virus is not a major determinant of a functional response to an HDACi.

HIV-1 establishes infection in astrocytes and macroage-lineage cells of the central nervous system (CNS). Certain antiretroviral drugs (ARVs) can penetrate the CNS, and are therefore often used in neurologically active combined antiretroviral therapy (Neuro-cART) regimens, but their relative activity in the different susceptible CNS cell populations is unknown. Here, we determined the HIV-1 inhibitory activity of CNS-penetrating ARVs in astrocytes and macrophage-lineage cells. Primary human fetal astrocytes (PFA) and the SVG human astrocyte cell line were used as in vitro models for astrocyte infection, and monocyte-derived macrophages (MDM) were used as an in vitro model for infection of macrophage-lineage cells. The CNS-penetrating ARVs tested were the nucleoside reverse transcriptase inhibitors (NRTIs) abacavir (ABC), lamivudine (3TC), stavudine (d4T) and zidovudine (ZDV), the non-NRTIs efavirenz (EFV), etravirine (ETR) and nevirapine (NVP), and the integrase inhibitor raltegravir (RAL). Drug inhibition assays were performed using single-round HIV-1 entry assays with luciferase viruses pseudotyped with HIV-1 YU-2 envelope or vesicular stomatitis virus G protein (VSV-G). All the ARVs tested could effectively inhibit HIV-1 infection in macrophages, with EC90s below concentrations known to be achievable in the cerebral spinal fluid (CSF). Most of the ARVs had similar potency in astrocytes, however the NRTIs 3TC, d4T and ZDV had insufficient HIV-1 inhibitory activity in astrocytes, with EC90s 12-, 187- and 110-fold greater than achievable CSF concentrations, respectively. Our data suggest that 3TC, d4T and ZDV may not adequately target astrocyte infection in vivo, which has potential implications for their inclusion in Neuro-cART regimens.

Aging is associated with immune dysfunction and the related development of conditions with an inflammatory pathogenesis. Some of these immune changes are also observed in HIV infection, but the interaction between immune changes with aging and HIV infection are unknown. Whilst sex differences in innate immunity are recognized, little research into innate immune aging has been performed on women.This cross-sectional study of HIV positive and negative women used whole blood flow cytometric analysis to characterize monocyte and CD8(+) T cell subsets. Plasma markers of innate immune activation were measured using standard ELISA-based assays.HIV positive women exhibited elevated plasma levels of the innate immune activation markers CXCL10 (p

HIV-1 infection increases the risk and severity of malaria by poorly defined mechanisms. We investigated the effect of HIV-1(Ba-L) infection of monocyte-derived macrophages (MDM) on phagocytosis of opsonised P. falciparum infected erythrocytes (IE) and subsequent proinflammatory cytokine secretion. Compared to mock-infected MDM, HIV-1 infection significantly inhibited phagocytosis of IE (median (IQR) (10 (0-28) versus (34 (27-108); IE internalised/100 MDM; p = 0.001) and decreased secretion of IL-6 (1,116 (352-3,387) versus 1,552 (889-6,331); pg/mL; p = 0.0078) and IL-1β (16 (7-21) versus 33 (27-65); pg/mL; p = 0.0078). Thus inadequate phagocytosis and cytokine production may contribute to impaired control of malaria in HIV-1 infected individuals.

CD163, a haptoglobin-hemoglobin (Hp-Hb) scavenger receptor, expressed by monocytes and macrophages, is important in resolution of inflammation. Age-related non-AIDS co-morbidities in HIV-infected individuals, particularly dementia and cardiovascular disease, result in part from effects of HIV-1 infection on monocyte and macrophage biology. CD163 co-expression on CD14+CD16++ monocytes has been proposed as a useful biomarker for HIV-1 disease progression and the presence of HIV associated dementia. Here we investigated CD163 expression on monocyte subsets ex vivo, on cultured macrophages, and soluble in plasma, in the setting of HIV-1 infection. Whole blood immunophenotyping revealed CD163 expression on CD14++CD16- monocytes but not on CD14+CD16++ monocytes (P = 0.004), supported by CD163 mRNA levels. Incubation with M-CSF induced CD163 protein expression on CD14+CD16++ monocytes to the same extent as CD14++CD16- monocytes. CD163 expression on CD14++CD16+ monocytes from HIV-infected subjects was significantly higher than from uninfected individuals, with a trend towards increased expression on CD14++CD16- monocytes (P = 0.019 and 0.069 respectively), which is accounted for by HIV-1 therapy including protease inhibitors. Shedding of CD163 was shown to predominantly occur from the CD14++CD16- subset after Ficoll isolation and LPS stimulation. Soluble CD163 concentration in plasma from HIV-1 infected donors was similar to HIV-1 uninfected donors. Monocyte CD163 expression in HIV-1 infected patients showed a complicated relationship with classical measures of disease progression. Our findings clarify technical issues regarding CD163 expression on monocyte subsets and further elucidates its role in HIV-associated inflammation by demonstrating that CD163 is readily lost from CD14++CD16- monocytes and induced in pro-inflammatory CD14+CD16++ monocytes by M-CSF. Our data show that all monocyte subsets are potentially capable of differentiating into CD163-expressing anti-inflammatory macrophages given appropriate stimuli. Levels of CD163 expression on monocytes may be a potential biomarker reflecting efforts by the immune system to resolve immune activation and inflammation in HIV-infected individuals.

HIV-1 infection increases the risk and severity of malaria by poorly defined mechanisms. We investigated the effect of HIV- 1Ba-L infection of monocyte-derived macrophages (MDM) on phagocytosis of opsonised P. falciparum infected erythrocytes (IE) and subsequent proinflammatory cytokine secretion. Compared to mock-infected MDM, HIV-1 infection significantly inhibited phagocytosis of IE (median (IQR) (10 (0-28) versus (34 (27-108); IE internalised/100 MDM; p = 0.001) and decreased secretion of IL-6 (1,116 (352-3,387) versus 1,552 (889-6,331); pg/mL; p = 0.0078) and IL-1β (16 (7-21) versus 33 (27-65); pg/ mL; p = 0.0078). Thus inadequate phagocytosis and cytokine production may contribute to impaired control of malaria in HIV-1 infected individuals. [ABSTRACT FROM AUTHOR]

CD163, a haptoglobin-hemoglobin (Hp-Hb) scavenger receptor, expressed by monocytes and macrophages, is important in resolution of inflammation. Age-related non-AIDS co-morbidities in HIV-infected individuals, particularly dementia and cardiovascular disease, result in part from effects of HIV-1 infection on monocyte and macrophage biology. CD163 coexpression on CD14+CD16++ monocytes has been proposed as a useful biomarker for HIV-1 disease progression and the presence of HIV associated dementia. Here we investigated CD163 expression on monocyte subsets ex vivo, on cultured macrophages, and soluble in plasma, in the setting of HIV-1 infection. Whole blood immunophenotyping revealed CD163 expression on CD14++CD16- monocytes but not on CD14+CD16++ monocytes (P = 0.004), supported by CD163 mRNA levels. Incubation with M-CSF induced CD163 protein expression on CD14+CD16++ monocytes to the same extent as CD14++CD162 monocytes. CD163 expression on CD14++CD16+ monocytes from HIV-infected subjects was significantly higher than from uninfected individuals, with a trend towards increased expression on CD14++CD162 monocytes (P = 0.019 and 0.069 respectively), which is accounted for by HIV-1 therapy including protease inhibitors. Shedding of CD163 was shown to predominantly occur from the CD14++CD162 subset after Ficoll isolation and LPS stimulation. Soluble CD163 concentration in plasma from HIV-1 infected donors was similar to HIV-1 uninfected donors. Monocyte CD163 expression in HIV-1 infected patients showed a complicated relationship with classical measures of disease progression. Our findings clarify technical issues regarding CD163 expression on monocyte subsets and further elucidates its role in HIV-associated inflammation by demonstrating that CD163 is readily lost from CD14++CD162 monocytes and induced in pro-inflammatory CD14+CD16++ monocytes by M-CSF. Our data show that all monocyte subsets are potentially capable of differentiating into CD163-expressing anti-inflammatory macrophages given appropriate stimuli. Levels of CD163 expression on monocytes may be a potential biomarker reflecting efforts by the immune system to resolve immune activation and inflammation in HIV-infected individuals. [ABSTRACT FROM AUTHOR]

The aim of this meta-analysis was to assess the association of general anesthesia (GA) exposure with the risk of POD in this patient population. Databases including Medline, EMBASE, Cochrane library, and Google Scholar were searched from inception to December 2022. Analysis of 17 studies published between 2015 and 2021 involving 10,678 individuals revealed an association of GA exposure with an elevated risk of POD [odd ratio (OR) = 1.846, 95% CI 1.329 to 2.563, p = 0.0003, I2 = 68.4%, 10,678 patients]. Subgroup analysis of the diagnostic methods also demonstrated a positive correlation between GA exposure and POD risk when validated methods were used for POD diagnosis (OR = 2.199, 95% CI 1.46 to 3.31, p = 0.0002). Meta-regression analyses showed no significant impact of age, male proportion, and sample size on the correlation between GA and the risk of POD. The reported overall incidence of POD from the included studies regardless of the type of anesthesia was between 0.8 and 27%. Our meta-analysis showed a pooled incidence of 10.3% (95% CI 7% to 15%). This meta-analysis suggested an association of general anesthesia with an elevated risk of postoperative delirium, implying the necessity of implementing appropriate prophylactic strategies against this complication when general anesthesia was used in this clinical setting. [ABSTRACT FROM AUTHOR]

Head and neck cancer (HNC) is a prevalent malignancy with a poor prognosis, necessitating the identification of prognostic biomarkers to guide management. The geriatric nutritional risk index (GNRI), calculated from serum albumin and body weight, may predict survival in patients with HNC. We performed a systematic review and meta-analysis to clarify this relationship. Databases were searched for studies examining the association between pretreatment GNRI and overall survival in patients with HNC. Ten studies with 2793 patients were included. Meta-analysis demonstrated that low GNRI was associated with significantly worse overall survival compared to high GNRI (hazard ratio [HR]:2.84, 95% CI 2.07–3.91, p < 0.00001). Older age (HR:1.73; 95% CI, 1.35–2.22; p < 0.0001), male sex (HR:1.7; 95% CI, 1.12–2.6; p = 0.01), advanced tumor stage (HR: 2.5; 95% CI, 1.72–3.63; p < 0.00001), and higher T-/N-stage (HR = 1.69 and 1.98, respectively) were also predictive of unfavorable outcomes. The GNRI had the highest HR, suggesting potent predictive ability. Despite limitations, including retrospective design and potential publication bias, our study indicates that low pretreatment GNRI predicts poor overall survival in patients with HNC. The GNRI is an inexpensive, routinely available biomarker that could improve prognostication and guide management decisions. Additional research is warranted to validate these findings. [ABSTRACT FROM AUTHOR]

This meta-analysis aimed to assess the clinical association of the preoperative prognostic nutritional index (pre-PNI) with the risk of postoperative acute kidney injury. Four databases (e.g., Medline) were searched from inception to December 2022 to investigate the association between pre-PNI (i.e., low vs. high) and PO-PNI as well as the correlation between pre-PNI and other postoperative prognostic indices. Overall, 13 observational studies, including 9185 patients, were eligible for analysis. A low PNI was related to increased risks of PO-AKI [odd ratio (OR) = 1.65, p = 0.001, 3811 patients], postoperative infection (OR = 2.1, p < 0.00001, 2291 patients), and mortality (OR = 1.93, p < 0.0001, 2159 patients). Albeit statistically nonsignificant, a trend was noted, linking a low PNI to higher risks of postoperative bleeding (OR = 2.5, p = 0.12, 1157 patients) and stroke (OR = 1.62, p = 0.07, 2036 patients). Pooled results revealed a prolonged intensive care unit (ICU) stay in patients with low PNIs compared to those with high PNIs (MD: 0.98 days, p = 0.02, 2209 patients) without a difference in hospital stay between the two groups (MD: 1.58 days, p = 0.35, 2249 patients). This meta-analysis demonstrated an inverse correlation between PNI and the risks of PO-AKI, postoperative infection, and mortality, as well as the length of ICU stay, which warrants further investigations for verification. [ABSTRACT FROM AUTHOR]

Interferons (IFNs) are cytokines secreted by infected cells that can interfere with viral replication. Besides activating antiviral defenses, type I IFNs also exhibit diverse biological functions. IFN-β has been shown to have a protective effect against neurotoxic and inflammatory insults on neurons. Therefore, we aimed to investigate the possible role of IFN-β in reducing mechanical allodynia caused by Complete Freund's Adjuvant (CFA) injection in rats. We assessed the antinociceptive effect of intrathecal IFN-β in naïve rats and the rats with CFA–induced inflammatory pain. After the behavioral test, the spinal cords of the rats were harvested for western blot and immunohistochemical double staining. We found that intrathecal administration of IFN-β in naïve rats can significantly increase the paw withdrawal threshold and paw withdrawal latency. Further, the intrathecal injection of a neutralizing IFN-β antibody can reduce the paw withdrawal threshold and paw withdrawal latency, suggesting that IFN-β is produced in the spinal cord in normal conditions and serves as a tonic inhibitor of pain. In addition, intrathecal injection of IFN-β at dosages from 1000 U to 10000 U demonstrates a significant transient dose-dependent inhibition of CFA-induced inflammatory pain. This analgesic effect is reversed by intrathecal naloxone, suggesting that IFN-β produces an analgesic effect through central opioid receptor-mediated signaling. Increased expression of phospho-µ-opioid receptors after IFN-β injection was observed on western blot, and immunohistochemical staining showed that µ-opioids co-localized with IFN-α/βR in the dorsal horn of the spinal cord. The findings of this study demonstrate that the analgesic effect of IFN-β is through µ-opioid receptors activation in spial cord. [ABSTRACT FROM AUTHOR]

P2Y12 blockade improves patient outcomes after myocardial infarction. As well as antithrombotic effects, anti-inflammatory effects may contribute to this beneficial clinical outcome. Here we aimed to identify potential anti-inflammatory effects of P2Y12 receptor blockers on monocytes and macrophages. Using flow cytometry, migration assays, flow chambers and RNA microarrays, we investigated the effects of adenosine diphosphate (ADP) and P2Y12 receptor blockers on blood monocytes, THP-1 monocytes and THP-1 monocytes after differentiation to macrophages. P2Y12 -expressing platelets can form aggregates with monocytes in circulating blood. Mediated by platelets, ADP results in activation of the integrin receptor Mac-1 on blood monocytes, as detected by the conformation-specific single-chain antibody MAN-1. Via the same association with platelets, THP-1 monocyte adhesion to the endothelial intercellular adhesion molecule 1 (ICAM-1) is induced by ADP. P2Y12 receptor blockers prevent these ADP effects on monocytes. Interestingly, in contrast to THP-1 monocytes, THP-1 monocytes, after differentiation to macrophages, directly expressed the P2Y12 receptor and consequently ADP was found to be a potent chemoattractant. Again, P2Y12 receptor blockers antagonised this effect. Accordingly, stimulation of THP-1 macrophages with ADP caused a substantial change in gene expression pattern and upregulation of several genes associated with inflammation and atherogenesis. These data establish novel anti-inflammatory effects of P2Y12 receptor blockers on monocytes and macrophages, which are expected to contribute to cardiovascular risk reduction. [ABSTRACT FROM AUTHOR]

Background: The explanation of epidural analgesia by anesthesiologist would often begin after the parturient is admitted to the hospital. Because of labor pain, the decision of receiving epidural analgesia would often be made by the family members, instead of the parturient herself. We aimed to test whether earlier prenatal shared decision-making (SDM) interventions increase parturient's comprehension and satisfaction of epidural labor analgesia, compared to conventional explanation after labor pain begun. Methods: During the 28th week of gestation, we provided the SDM parturient health education as well as a leaflet with quick response codes. Scanning the code would link to education videoclips which explained what epidural analgesia is and its advantages and disadvantages. Original routine practice group parturients received explanation of analgesia after admission for delivery. To measure the satisfaction of labor pain service, the accessibility of information, and the communication with medical staff, we designed a questionnaire with reference to (1) Pregnancy and Maternity Care Patients' Experiences Questionnaire (PreMaPEQ), (2) Preterm Birth Experience and Satisfaction Scale (P-BESS), and (3) Women's Views of Birth Labor Satisfaction Questionnaire (WOMBLSQ). The questionnaire was amended after a pretest involving 30 parturients who had received epidural analgesia. Scree test analysis and exploratory factor analysis were performed; then, the questionnaire was revised again. A total of 200 valid questionnaires were collected—100 each from the original routine practice group and the SDM group. Results: The SDM group reported significantly higher satisfaction with and understanding of epidural analgesia, and a significantly higher satisfaction with the information received, and the quality of pain relief. After SDM intervention, significant increasement of the average satisfaction scores in question "my epidural is effective" (9.10%; mean difference: 0.38; 95% confidence interval, 0.17 ~ 0.59; p < 0.001) and "The effect of epidural is just as what I have expected" (10.41%; mean difference: 0.41; 95% confidence interval, 0.18 ~ 0.64; p < 0.001) was demonstrated. Conclusions: An earlier prenatal SDM intervention with sufficient information through videoclips increased parturients' comprehensions and satisfaction of epidural analgesia service. Trial registration: ISRCTN registry, 14,256,563. Registered April 1st, 2020 (10.1186/ISRCTN14256563). [ABSTRACT FROM AUTHOR]

The main goal of this study is to investigate whether higher (cost-effective) operational efficiency in restaurants can be achieved without lowering the perceived level of service quality. This study also investigates the importance of restaurants' size on operational efficiency and on the perceived level of service quality. We present the methodological procedures used to investigate the relationships among restaurants' operational efficiency, size, and service quality after presenting the conceptualization of the cost-effective service excellence (CESE) research construct. The restaurants' efficiency was assessed using Data Envelopment Analyses and the DINESERV tool was implemented to analyse guests' perceptions of service quality. Guests of low- and high-efficient restaurants perceive service quality based on the same quality dimensions. Based on the structural equation modelling, it is evident that CESE can be achieved in the restaurant industry. The restaurant size has proven to influence restaurants' operational efficiency and guests' quality perceptions. [ABSTRACT FROM AUTHOR]

Histone deacetylase inhibitors (HDACi) can induce human immunodeficiency virus (HIV) transcription from the HIV long terminal repeat (LTR). However, ex vivo and in vivo responses to HDACi are variable and the activity of HDACi in cells other than T-cells have not been well characterised. Here, we developed a novel assay to determine the activity of HDACi on patient-derived HIV LTRs in different cell types. HIV LTRs from integrated virus were amplified using triple-nested Alu-PCR from total memory CD4+ T-cells (CD45RO+) isolated from HIV-infected patients prior to and following suppressive antiretroviral therapy. NL4-3 or patient-derived HIV LTRs were cloned into the chromatin forming episomal vector pCEP4, and the effect of HDACi investigated in the astrocyte and epithelial cell lines SVG and HeLa, respectively. There were no significant differences in the sequence of the HIV LTRs isolated from CD4+ T-cells prior to and after 18 months of combination antiretroviral therapy (cART). We found that in both cell lines, the HDACi panobinostat, trichostatin A, vorinostat and entinostat activated patient-derived HIV LTRs to similar levels seen with NL4-3 and all patient derived isolates had similar sensitivity to maximum HDACi stimulation. We observed a marked difference in the maximum fold induction of luciferase by HDACi in HeLa and SVG, suggesting that the effect of HDACi may be influenced by the cellular environment. Finally, we observed significant synergy in activation of the LTR with vorinostat and the viral protein Tat. Together, our results suggest that the LTR sequence of integrated virus is not a major determinant of a functional response to an HDACi. [ABSTRACT FROM AUTHOR]

Astrocytes are extensively infected with HIV-1 in vivo and play a significant role in the development of HIV-1-associated neurocognitive disorders. Despite their extensive infection, little is known about how astrocytes become infected, since they lack cell surface CD4 expression. In the present study, we investigated the fate of HIV-1 upon infection of astrocytes. Astrocytes were found to bind and harbor virus followed by biphasic decay, with HIV-1 detectable out to 72 hours. HIV-1 was observed to associate with CD81-lined vesicle structures. shRNA silencing of CD81 resulted in less cell-associated virus but no loss of co-localization between HIV-1 and CD81. Astrocytes supported trans-infection of HIV-1 to T-cells without de novo virus production, and the virus-containing compartment required 37°C to form, and was trypsin-resistant. The CD81 compartment observed herein, has been shown in other cell types to be a relatively protective compartment. Within astrocytes, this compartment may be actively involved in virus entry and/or spread. The ability of astrocytes to transfer virus, without de novo viral synthesis suggests they are capable of sequestering and protecting virus and thus, they could potentially facilitate viral dissemination in the CNS. [ABSTRACT FROM AUTHOR]

This paper theoretically studies how unfunded pay-as-you-go social security affects economic growth, the fertility rate, and welfare in a neoclassical growth model. In addition, this paper considers a more general form of child-rearing cost, which is a mixture of time and money. The first observation is that whether the fertility rate increases or not by the expansion of the pay-as-you-go social security depends on (1) the size of the monetary child-rearing cost relative to the time spent on child-rearing and (2) the current fertility and interest rate in laissez faire. The second observation is that income per worker can increase by an expansion in pay-as-you-go social security when the output elasticity of capital is sufficiently small and the payroll tax rate is high. The last finding is that welfare can be improved even though capital is underaccumulated in an economy. [ABSTRACT FROM AUTHOR]

HIV-1 establishes infection in astrocytes and macroage-lineage cells of the central nervous system (CNS). Certain antiretroviral drugs (ARVs) can penetrate the CNS, and are therefore often used in neurologically active combined antiretroviral therapy (Neuro-cART) regimens, but their relative activity in the different susceptible CNS cell populations is unknown. Here, we determined the HIV-1 inhibitory activity of CNS-penetrating ARVs in astrocytes and macrophage-lineage cells. Primary human fetal astrocytes (PFA) and the SVG human astrocyte cell line were used as in vitro models for astrocyte infection, and monocyte-derived macrophages (MDM) were used as an in vitro model for infection of macrophage-lineage cells. The CNS-penetrating ARVs tested were the nucleoside reverse transcriptase inhibitors (NRTIs) abacavir (ABC), lamivudine (3TC), stavudine (d4T) and zidovudine (ZDV), the non-NRTIs efavirenz (EFV), etravirine (ETR) and nevirapine (NVP), and the integrase inhibitor raltegravir (RAL). Drug inhibition assays were performed using single-round HIV-1 entry assays with luciferase viruses pseudotyped with HIV-1 YU-2 envelope or vesicular stomatitis virus G protein (VSV-G). All the ARVs tested could effectively inhibit HIV-1 infection in macrophages, with EC90s below concentrations known to be achievable in the cerebral spinal fluid (CSF). Most of the ARVs had similar potency in astrocytes, however the NRTIs 3TC, d4T and ZDV had insufficient HIV-1 inhibitory activity in astrocytes, with EC90s 12-, 187- and 110-fold greater than achievable CSF concentrations, respectively. Our data suggest that 3TC, d4T and ZDV may not adequately target astrocyte infection in vivo, which has potential implications for their inclusion in Neuro-cART regimens. [ABSTRACT FROM AUTHOR]

Background: Aging is associated with immune dysfunction and the related development of conditions with an inflammatory pathogenesis. Some of these immune changes are also observed in HIV infection, but the interaction between immune changes with aging and HIV infection are unknown. Whilst sex differences in innate immunity are recognized, little research into innate immune aging has been performed on women. Methods: This cross-sectional study of HIV positive and negative women used whole blood flow cytometric analysis to characterize monocyte and CD8+ T cell subsets. Plasma markers of innate immune activation were measured using standard ELISA-based assays. Results: HIV positive women exhibited elevated plasma levels of the innate immune activation markers CXCL10 (p<0.001), soluble CD163 (sCD163, p = 0.001), sCD14 (p = 0.022), neopterin (p = 0.029) and an increased proportion of CD16+ monocytes (p = 0.009) compared to uninfected controls. Levels of the innate immune aging biomarkers sCD163 and the proportion of CD16+ monocytes were equivalent to those observed in HIV negative women aged 14.5 and 10.6 years older, respectively. CXCL10 increased with age at an accelerated rate in HIV positive women (p = 0.002) suggesting a synergistic effect between HIV and aging on innate immune activation. Multivariable modeling indicated that age-related increases in innate immune biomarkers CXCL10 and sCD163 are independent of senescent changes in CD8+ T lymphocytes. Conclusions: Quantifying the impact of HIV on immune aging reveals that HIV infection in women confers the equivalent of a 10-14 year increase in the levels of innate immune aging markers. These changes may contribute to the increased risk of inflammatory age-related diseases in HIV positive women. [ABSTRACT FROM AUTHOR]