bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma inflammatory cytokines and treatment-resistant depression with comorbid pain: improvement by ketamine
Authors: Zhou Yanling , Wang Chengyu , Lan Xiaofeng , Li Hanqiu , Chao Ziyuan , Ning Yuping
Published: September 2021

Background

Treatment-resistant depression (TRD) and pain frequently coexist clinically. Ketamine has analgesic and antidepressant effects, but few studies have evaluated individual differences in antidepressant outcomes to repeated ketamine in TRD patients with comorbid pain. Our aims were to determine the difference in ketamine’s antidepressant effects in TRD patients with or without pain and then to examine whether inflammatory cytokines might contribute to ketamine’s effect.

Methods

Sixty-six patients with TRD received six infusions of ketamine. Plasma levels of 19 inflammatory cytokines were assessed at baseline and post-infusion (day 13 and day 26) using the Luminex assay. Plasma inflammatory cytokines of sixty healthy controls (HCs) were also examined.

Results

TRD patients with pain had a higher antidepressant response rate (χ2 = 4.062, P = 0.044) and remission rate (χ2 = 4.062, P = 0.044) than patients without pain. Before ketamine treatment, GM-CSF and IL-6 levels were higher in the pain group than in the non-pain and HC groups. In the pain group, levels of TNF-α and IL-6 at day 13 and GM-CSF, fractalkine, IFN-γ, IL-10, MIP-3α, IL-12P70, IL-17α, IL-1β, IL-2, IL-4, IL-23, IL-5, IL-6, IL-7, MIP-1β, and TNF-α at day 26 were lower than those at baseline; in the non-pain group, TNF-α levels at day 13 and day 26 were lower than those at baseline. In the pain group, the changes of IL-6 were associated with improvement in pain intensity (β = 0.333, P = 0.001) and depressive symptoms (β = 0.478, P = 0.005) at day 13. Path analysis showed the direct (β = 2.995, P = 0.028) and indirect (β = 0.867, P = 0.042) effects of changes of IL-6 on improvement in depressive symptoms both were statistically significant.

Conclusion

This study suggested that an elevated inflammatory response plays a critical role in individual differences in TRD patients with or without pain. Ketamine showed great antidepressant and analgesic effects in TRD patients with pain, which may be related to its effects on modulating inflammation.

Trial registration

ChiCTR, ChiCTR-OOC-17012239. Registered on 26 May 2017
Changes in substance use during outpatient treatment for substance use disorders: a prospective Norwegian cohort study from 2016 to 2020
Authors: Vold Jørn Henrik , Chalabianloo Fatemeh , Aas Christer F. , Løberg Else-Marie , Johansson Kjell Arne , Fadnes Lars Thore
Published: September 2021

Background

Continuous use of amphetamines, alcohol, benzodiazepines, cannabis, cocaine, or opioids contributes to health impairments, increased morbidity, and overdose deaths among patients with substance use disorders (SUDs). This study evaluates the impact of inpatient detoxification, injecting substance use, age, and gender on substance use over time among patients undergoing outpatient SUD treatment.

Methods

We used data from a cohort of SUD patients in Norway obtained from health assessments of self-reported substance use and sociodemographic and clinical factors. A total of 881 substance use measurements, including substances and frequency of use, were assessed for 708 SUD patients in 2016–2020. Of those, 171 patients provided two or more substance use measurements. The total substance use was calculated, creating a substance use severity index (SUSI), ranging from zero (no use) to one (daily use of all substances). We defined baseline as the first substance use measurement when the measurements were listed chronologically. Time was defined as years from baseline. We used a linear mixed model to analyze the SUSI at baseline and over time, and its associations with inpatient detoxification, injecting substance use, gender, and age, presented with coefficients and 95% confidence intervals (CI).

Results

No longitudinal changes in the SUSI were found compared with baseline (change in SUSI (cSUSI): 0.04, 95% CI: − 0.05;0.13, p = 0.397). Likewise, “inpatient detoxification” was not associated with changes in the SUSI compared with “no inpatient detoxification” (cSUSI: 0.00, 95% CI: − 0.04;0.04, p = 0.952). However, injecting substances were associated with a higher SUSI than not injecting substances at baseline (difference in SUSI: 0.19, 95% CI: 0.16;0.21, p = < 0.001), and starting to inject substances was associated with increasing SUSI over time compared with not starting to inject substances (cSUSI: 0.11, 95% CI: 0.07;0.15, p = < 0.001). Gender was not significantly associated with changes in the SUSI (cSUSI: − 0.04, 95% CI: − 0.07;0.00, p = 0.052), while patients over 60 years of age had a lower SUSI than those under the age of 30 at baseline (difference in SUSI: − 0.08, 95% CI: − 0.14;− 0.01, p = 0.018), with no change over time (cSUSI: − 0.05, 95% CI: − 0.16;0.05, p = 0.297).

Conclusion

The present study demonstrates that inpatient detoxification was not associated with substance use changes over time for patients undergoing outpatient SUD treatment. Otherwise, injecting substance use was a particular risk factor for a high level of substance use. Future research needs to evaluate the impact of other treatment approaches on substance use, ideally in randomized controlled trials.
Effects of single and multiple transplantations of human umbilical cord mesenchymal stem cells on the recovery of ovarian function in the treatment of premature ovarian failure in mice
Authors: Lv Xiaodan , Guan Chunyi , Li Ying , Su Xing , Zhang Lu , Wang Xueqin , Xia Hong-Fei , Ma Xu
Published: September 2021

Background

Currently, there is no effective treatment for premature ovarian failure (POF), and stem cell therapy is considered the most promising treatment. Human umbilical cord blood mesenchymal stem cells (hUC-MSCs) have shown good regenerative ability in various diseases, including POF; however, their underlying mechanism and dosage for POF treatment remain unclear. This study aimed to compare the effect of single and multiple injections of hUC-MSCs on ovarian function repair in chemotherapy-induced POF.

Methods

Female mice were intraperitoneally injected with 30 mg/kg busulfan and 120 mg/kg cyclophosphamide (CTX) to induce POF. In the single hUC-MSC injection group, hUC-MSCs were transplanted into mice D7 after CTX and busulfan administration, while in the multiple injection group, hUC-MSCs were transplanted on D7, D14, and D21 after CTX and busulfan administration. We evaluated the ovarian morphology, fertility, follicle-stimulating hormone and estradiol concentrations, follicle count, POF model, and cell transplantation results. In addition, real-time polymerase chain reaction, immunohistochemistry, and miRNA and mRNA chips were used to evaluate the effect of the cell therapy.

Results

Ovary size, number of follicle at all developmental stages, and fertility were significantly reduced in the POF group compared with the control. Under hUC-MSC treatment, the ovarian morphology and follicle count were significantly restored, and fertility was significantly increased. By comparing the single and multiple hUC-MSC injection groups, we found that the anti-Müllerian hormone and Ki-67 levels were significantly increased in the multiple hUC-MSC group on D60 after chemotherapy. The expression of stimulating hormone receptors, inhibin α, and inhibin β was significantly restored, and the therapeutic effect was superior to that of the single hUC-MSC injection group.

Conclusion

These results indicate that hUC-MSCs can restore the structure of injured ovarian tissue and its function in chemotherapy-induced POF mice and ameliorate fertility. Multiple hUC-MSC transplantations have a better effect on the recovery of ovarian function than single hUC-MSC transplantation in POF.
Identification of persistent and resolving subphenotypes of acute hypoxemic respiratory failure in two independent cohorts
Authors: Sathe Neha A. , Zelnick Leila R. , Mikacenic Carmen , Morrell Eric D. , Bhatraju Pavan K. , McNeil J. Brennan , Kosamo Susanna , Hough Catherine L. , Liles W. Conrad , Ware Lorraine B. , Wurfel Mark M.
Published: September 2021

Background

Acute hypoxemic respiratory failure (HRF) is associated with high morbidity and mortality, but its heterogeneity challenges the identification of effective therapies. Defining subphenotypes with distinct prognoses or biologic features can improve therapeutic trials, but prior work has focused on ARDS, which excludes many acute HRF patients. We aimed to characterize persistent and resolving subphenotypes in the broader HRF population.

Methods

In this secondary analysis of 2 independent prospective ICU cohorts, we included adults with acute HRF, defined by invasive mechanical ventilation and PaO2-to-FIO2 ratio ≤ 300 on cohort enrollment (n = 768 in the discovery cohort and n = 1715 in the validation cohort). We classified patients as persistent HRF if still requiring mechanical ventilation with PaO2-to-FIO2 ratio ≤ 300 on day 3 following ICU admission, or resolving HRF if otherwise. We estimated relative risk of 28-day hospital mortality associated with persistent HRF, compared to resolving HRF, using generalized linear models. We also estimated fold difference in circulating biomarkers of inflammation and endothelial activation on cohort enrollment among persistent HRF compared to resolving HRF. Finally, we stratified our analyses by ARDS to understand whether this was driving differences between persistent and resolving HRF.

Results

Over 50% developed persistent HRF in both the discovery (n = 386) and validation (n = 1032) cohorts. Persistent HRF was associated with higher risk of death relative to resolving HRF in both the discovery (1.68-fold, 95% CI 1.11, 2.54) and validation cohorts (1.93-fold, 95% CI 1.50, 2.47), after adjustment for age, sex, chronic respiratory illness, and acute illness severity on enrollment (APACHE-III in discovery, APACHE-II in validation). Patients with persistent HRF displayed higher biomarkers of inflammation (interleukin-6, interleukin-8) and endothelial dysfunction (angiopoietin-2) than resolving HRF after adjustment. Only half of persistent HRF patients had ARDS, yet exhibited higher mortality and biomarkers than resolving HRF regardless of whether they qualified for ARDS.

Conclusion

Patients with persistent HRF are common and have higher mortality and elevated circulating markers of lung injury compared to resolving HRF, and yet only a subset are captured by ARDS definitions. Persistent HRF may represent a clinically important, inclusive target for future therapeutic trials in HRF.
Simple compared to covariate-constrained randomization methods in balancing baseline characteristics: a case study of randomly allocating 72 hemodialysis centers in a cluster trial
Authors: Al-Jaishi Ahmed A. , Dixon Stephanie N. , McArthur Eric , Devereaux P. J. , Thabane Lehana , Garg Amit X.
Published: September 2021

Background and aim

Some parallel-group cluster-randomized trials use covariate-constrained rather than simple randomization. This is done to increase the chance of balancing the groups on cluster- and patient-level baseline characteristics. This study assessed how well two covariate-constrained randomization methods balanced baseline characteristics compared with simple randomization.

Methods

We conducted a mock 3-year cluster-randomized trial, with no active intervention, that started April 1, 2014, and ended March 31, 2017. We included a total of 11,832 patients from 72 hemodialysis centers (clusters) in Ontario, Canada. We randomly allocated the 72 clusters into two groups in a 1:1 ratio on a single date using individual- and cluster-level data available until April 1, 2013. Initially, we generated 1000 allocation schemes using simple randomization. Then, as an alternative, we performed covariate-constrained randomization based on historical data from these centers. In one analysis, we restricted on a set of 11 individual-level prognostic variables; in the other, we restricted on principal components generated using 29 baseline historical variables.

We created 300,000 different allocations for the covariate-constrained randomizations, and we restricted our analysis to the 30,000 best allocations based on the smallest sum of the penalized standardized differences. We then randomly sampled 1000 schemes from the 30,000 best allocations. We summarized our results with each randomization approach as the median (25th and 75th percentile) number of balanced baseline characteristics. There were 156 baseline characteristics, and a variable was balanced when the between-group standardized difference was ≤ 10%.

Results

The three randomization techniques had at least 125 of 156 balanced baseline characteristics in 90% of sampled allocations. The median number of balanced baseline characteristics using simple randomization was 147 (142, 150). The corresponding value for covariate-constrained randomization using 11 prognostic characteristics was 149 (146, 151), while for principal components, the value was 150 (147, 151).

Conclusion

In this setting with 72 clusters, constraining the randomization using historical information achieved better balance on baseline characteristics compared with simple randomization; however, the magnitude of benefit was modest.
A comparison of PCR and ELISA methods to detect different stages of Plasmodium vivax in Anopheles arabiensis
Authors: Hendershot Allison L. , Esayas Endashaw , Sutcliffe Alice C. , Irish Seth R. , Gadisa Endalamaw , Tadesse Fitsum G. , Lobo Neil F.
Published: September 2021

Background

In characterizing malaria epidemiology, measuring mosquito infectiousness informs the entomological inoculation rate, an important metric of malaria transmission. PCR-based methods have been touted as more sensitive than the current “gold-standard” circumsporozoite (CSP) ELISA. Wider application of PCR-based methods has been limited by lack of specificity for the infectious sporozoite stage. We compared a PCR method for detecting the parasite’s mitochondrial (mt) cytochrome oxidase I (COX-I) gene with ELISA for detecting circumsporozoite protein for identification of different life stages of the parasite during development within a mosquito.

Methods

A PCR-based method targeting the Plasmodium mt COX-I gene was compared with the CSP ELISA method to assess infectivity in Anopheles arabiensis colony mosquitoes fed on blood from patients infected with Plasmodium vivax. Mosquitoes were tested at six post-infection time points (days 0.5, 1, 6, 9, 12, 15). The head and thorax and the abdomen for each specimen were tested separately with each method. Agreement between methods at each infection stage was measured using Cohen’s kappa measure of test association.

Results

Infection status of mosquitoes was assessed in approximately 90 head/thorax and 90 abdomen segments at each time point; in total, 538 head/thorax and 534 abdomen segments were tested. In mosquitoes bisected after 0.5, 1, and 6 days post-infection (dpi), the mt COX-I PCR detected Plasmodium DNA in both the abdomen (88, 78, and 67%, respectively) and head/thorax segments (69, 60, and 44%, respectively), whilst CSP ELISA detected sporozoites in only one abdomen on day 6 post-infection. PCR was also more sensitive than ELISA for detection of Plasmodium in mosquitoes bisected after 9, 12, and 15 dpi in both the head and thorax and abdomen. There was fair agreement between methods for time points 9–15 dpi (κ = 0.312, 95% CI: 0.230–0.394).

Conclusions

The mt COX-I PCR is a highly sensitive, robust method for detecting Plasmodium DNA in mosquitoes, but its limited Plasmodium life-stage specificity cannot be overcome by bisection of the head and thorax from the abdomen prior to PCR. Thus, the mt COX-I PCR is a poor candidate for identifying infectious mosquitoes.

Graphical Abstract
Recombinant antigens used as diagnostic tools for lymphatic filariasis
Authors: Pastor André Filipe , Silva Maressa Rhuama , dos Santos Wagner José Tenório , Rego Tamisa , Brandão Eduardo , de-Melo-Neto Osvaldo Pompilio , Rocha Abraham
Published: September 2021

Lymphatic filariasis (LF) is a parasitic disease caused by the worms Wuchereria bancrofti, Brugia malayi, or Brugia timori. It is a tropical and subtropical illness that affects approximately 67 million people worldwide and that still requires better diagnostic tools to prevent its spread and enhance the effectiveness of control procedures. Traditional parasitological tests and diagnostic methods based on whole protein extracts from different worms are known for problems related to sample time collection, sensitivity, and specificity. More recently, new diagnostic tools based on immunological methods using recombinant antigens have been developed. The current review describes the several recombinant antigens used as tools for lymphatic filariasis diagnosis in antigen and antibody capture assays, highlighting their advantages and limitations as well as the main commercial tests developed based on them. The literature chronology is from 1991 to 2021. First, it describes the historical background related to the identification of relevant antigens and the generation of the recombinant polypeptides used for the LF diagnosis, also detailing features specific to each antigen. The subsequent section then discusses the use of those proteins to develop antigen and antibody capture tests to detect LF. So far, studies focusing on antibody capture assays are based on 13 different antigens with at least six commercially available tests, with five proteins further used for the development of antigen capture tests. Five antigens explored in this paper belong to the SXP/RAL-2 family (BmSXP, Bm14, WbSXP-1, Wb14, WbL), and the others are BmShp-1, Bm33, BmR1, BmVAH, WbVAH, BmALT-1, BmALT-2, and Wb123. It is expected that advances in research with these antigens will allow further development of tests combining both sensitivity and specificity with low costs, assisting the Global Program to Eliminate Lymphatic Filariasis (GPELF).
Contrasting effects of the alkaloid ricinine on the capacity of Anopheles gambiae and Anopheles coluzzii to transmit Plasmodium falciparum
Authors: Hien Domonbabele F. D. S. , Paré Prisca S. L. , Cooper Amanda , Koama Benjamin K. , Guissou Edwige , Yaméogo Koudraogo B. , Yerbanga Rakiswendé S. , Farrell Iain W. , Ouédraogo Jean B. , Gnankiné Olivier , Ignell Rickard , Cohuet Anna , Dabiré Roch K. , Stevenson Philip C. , Lefèvre Thierry
Published: September 2021

Background

Besides feeding on blood, females of the malaria vector Anopheles gambiae sensu lato readily feed on natural sources of plant sugars. The impact of toxic secondary phytochemicals contained in plant-derived sugars on mosquito physiology and the development of Plasmodium parasites remains elusive. The focus of this study was to explore the influence of the alkaloid ricinine, found in the nectar of the castor bean Ricinus communis, on the ability of mosquitoes to transmit Plasmodium falciparum.

Methods

Females of Anopheles gambiae and its sibling species Anopheles coluzzii were exposed to ricinine through sugar feeding assays to assess the effect of this phytochemical on mosquito survival, level of P. falciparum infection and growth rate of the parasite.

Results

Ricinine induced a significant reduction in the longevity of both Anopheles species. Ricinine caused acceleration in the parasite growth rate with an earlier invasion of the salivary glands in both species. At a concentration of 0.04 g l−1 in An. coluzzii, ricinine had no effect on mosquito infection, while 0.08 g l−1 ricinine-5% glucose solution induced a 14% increase in An. gambiae infection rate.

Conclusions

Overall, our findings reveal that consumption of certain nectar phytochemicals can have unexpected and contrasting effects on key phenotypic traits that govern the intensity of malaria transmission. Further studies will be required before concluding on the putative role of ricinine as a novel control agent, including the development of ricinine-based toxic and transmission-blocking sugar baits. Testing other secondary phytochemicals in plant nectar will provide a broader understanding of the impact which plants can have on the transmission of vector-borne diseases.

Graphical abstract
High-frequency and activation of CD4+CD25+ T cells maintain persistent immunotolerance induced by congenital ALV-J infection
Authors: He Shuhai , Zheng Gaoying , Zhou Defang , Huang Li , Dong Jianguo , Cheng Ziqiang
Published: September 2021

Congenital avian leukosis virus subgroup J (ALV-J) infection can induce persistent immunotolerance in chicken, however, the underlying mechanism remains unclear. Here, we demonstrate that congenital ALV-J infection induces the production of high-frequency and activated CD4+CD25+Tregs that maintain persistent immunotolerance. A model of congenital infection by ALV-J was established in fertilized eggs, and hatched chicks showed persistent immunotolerance characterized by persistent viremia, immune organ dysplasia, severe imbalance of the ratio of CD4+/CD8+T cells in blood and immune organs, and significant decrease in CD3+T cells and Bu-1+B cells in the spleen. Concurrently, the mRNA levels of IL-2, IL-10, and IFN-γ showed significant fluctuations in immune organs. Moreover, the frequency of CD4+CD25+Tregs in blood and immune organs significantly increased, and the frequency of CD4+CD25+Tregs was positively correlated with changes in ALV-J load in immune organs. Interestingly, CD4+CD25+Tregs increased in the marginal zone of splenic nodules in ALV-J-infected chickens and dispersed to the germinal center. In addition, the proliferation and activation of B cells in splenic nodules was inhibited, and the number of IgM+and IgG+cells in the marginal zone significantly decreased. We further found that the mRNA levels of TGF- β and CTLA-4 in CD4+CD25+Tregs of ALV-J-infected chickens significantly increased. Together, high-frequency and activated CD4+CD25+Tregs inhibited B cells functions by expressing the inhibitory cytokine TGF-β and inhibitory surface receptor CTLA-4, thereby maintaining persistent immunotolerance in congenital ALV-J-infected chickens.
Comparison of different approaches to combined spinal epidural anesthesia (CSEA) under the guidance of ultrasound in cesarean delivery of obese patients: a randomized controlled trial
Authors: Zhou Yilu , Chen Wei , Zhou Shuangqiong , Tao Yiyi , Xu Zhendong , Liu Zhiqiang
Published: September 2021

Background

Combined spinal epidural anesthesia (CSEA) is commonly performed in cesarean deliveries. However, it is difficult to perform in obese parturients because of positioning challenges. The aim of this study was to compare the effect of different approaches to CSEA under the guidance of ultrasound.

Methods

One hundred obese patients (BMI ≥ 30 kg/m2) who underwent elective cesarean section were randomly enrolled. Patients were assigned to a median approach group and a paramedian approach group randomly. Clinical characteristics were compared between groups. First-attempt success rate, the median positioning time and total operation time, ultrasonic predicted anesthesia puncture depth, actual puncture depth, anesthesia adverse reactions, complications after anesthesia, and patients’ satisfaction with the epidural puncture were recorded.

Results

The first-attempt success rate was significantly different between the two groups [92% (46/50) vs. 76% (38/50), P  =  0.029]. The median positioning time and total operation time in the paramedian approach group were higher than those in the median approach group (227.7 s vs. 201.6 s, P  =  0.037; 251.3 s vs. 247.4 s, P  =  0.145). The incidence of postanesthesia complications in the paramedian approach group was significantly lower than that in the median approach group (2% vs. 12%, P  =  0.026), and patient satisfaction was higher in the paramedian approach group than in the median approach group (P  =  0.032).

Conclusion

The ultrasound-guided paramedian approach for CSEA is time-consuming, but it can effectively improve the success rate of the first puncture, reduce the incidence of anesthesia-related adverse reactions, and improve patient satisfaction.

Trial registration: This study was registered with the Chinese Clinical Trial Registry (ChiCTR1900024722) on July 24, 2019
Anesthetic management of super-elderly patients with remimazolam: a report of two cases
Authors: Nakayama Junko , Ogihara Tomomi , Yajima Rui , Innami Yasushi , Ouchi Takashi
Published: September 2021

Background

Remimazolam is a newly developed benzodiazepine with more rapid onset and offset of sedation effects than midazolam. We report elderly patients in whom a small dose of remimazolam was successfully used for general anesthesia.

Case presentation

Two elderly women (patients 1 and 2, aged 95 and 103 years, respectively) underwent hip fracture surgery under general anesthesia guided by bispectral index (BIS). Anesthesia was induced with 1.2 and 1.0 mg/kg/h and maintained with 0.2 and 0.1 mg/kg/h remimazolam, combined with fentanyl and remifentanil in patients 1 and 2, respectively. Their hemodynamics were stable with a small dose of vasopressor, and they awoke soon after the discontinuation of remimazolam without flumazenil reversal. Their postoperative courses were uneventful without any complications. Conversely, the remimazolam dose required to achieve adequate sedation were much lower than expected.

Conclusion

Remimazolam could be useful in general anesthesia, particularly for super-elderly patients. However, the appropriate dose for induction and maintenance of anesthesia should be carefully considered based on BIS or vital signs.
Interaction mechanism of collagen peptides with four phenolic compounds in the ethanol-water solution
Authors: Liu Xian , Li Xia , Huang Zhangjun , Liao Xuepin , Shi Bi
Published: September 2021

This study demonstrated the interaction mechanism of collagen peptides (CPs) with 4-ethylphenol (4-EP), phenol, guaiacol, and 4-ethylguaiacol (4-EG) in the ethanol-water solution. The ultraviolet visible spectroscopy, zeta potential tests and hydrogen nuclear magnetic spectroscopy manifested that CPs interacted with the phenolic compounds. Meanwhile, Isothermal titration calorimetry determination indicated that the CPs was hydrogen bonded with 4-EP in 52 %(v/v) ethanol-water solution, while the hydrophobic forces played a major role in the interaction of CPs with guaiacol and 4-EG, respectively. Moreover, hydrogen and hydrophobic bonds were involved in the interaction between CPs and phenol. Finally, Head Space-solid Phase Microextraction Gas Chromatography Mass Spectrometry analysis indicated that the content of phenolic compounds in model solution efficiently decreased with the presence of CPs. In the real liquor, it was found that the content of volatile compounds (including phenolic compounds) was obviously decreased after CPs added.
Groups 4 Health versus cognitive–behavioural therapy for depression and loneliness in young people: randomised phase 3 non-inferiority trial with 12-month follow-up
Authors: Cruwys Tegan , Haslam Catherine , Rathbone Joanne A. , Williams Elyse , Haslam S. Alexander , Walter Zoe C.
Published: September 2021

Background

Depression treatments are typically less effective for young people than for adults. However, treatments rarely target loneliness, which is a key risk factor in the onset, maintenance and development of depression.

Aims

This study evaluated the efficacy of a novel loneliness intervention, Groups 4 Health (G4H), relative to the best-practice treatment of cognitive–behavioural therapy (CBT) in reducing loneliness and depression over a 12-month period (Australian New Zealand Clinical Trial Registry: ACTRN12618000440224).

Method

The study was a phase 3 randomised non-inferiority trial comparing G4H with dose-controlled group CBT. Participants were 174 people aged 15–25 years experiencing loneliness and clinically significant symptoms of depression, who were not in receipt of adjunct treatment. Participants were recruited from mental health services in Southeast Queensland, Australia. Randomisation was conducted using computer software. Follow-up assessments and statistical analyses were masked to allocation. Both interventions consisted of five 75 min group-based psychotherapy sessions. The primary outcomes were depression and loneliness, with a non-inferiority margin of 2.20 for depression.

Results

The trial enrolled 174 participants between 24 April 2018 and 25 May 2019, with 84 in the G4H condition and 90 in the CBT condition. All randomised participants were included in the intention-to-treat analyses (n= 174). The pre–post effect sizes for depression weredG4H= −0.71 anddCBT= −0.91. For loneliness, they weredG4H= −1.07 anddCBT= −0.89. At 12-month follow-up, the absolute difference between groups on depression was 1.176 (95% CI −1.94 to 4.29) and on loneliness it was −0.679 (95% CI −1.43 to 0.07). No adverse effects were observed.

Conclusions

G4H was non-inferior to CBT for depression and showed a slight advantage over CBT for loneliness that emerged after treatment completion.
Implementing a Machine Learning Strategy to Predict Pathologic Response in Patients With Soft Tissue Sarcomas Treated With Neoadjuvant Chemotherapy
Authors: Crombé Amandine , Cousin Sophie , Spalato-Ceruso Mariella , Le Loarer François , Toulmonde Maud , Michot Audrey , Kind Michèle , Stoeckle Eberhard , Italiano Antoine
Published: September 2021

PURPOSE

Neoadjuvant chemotherapy (NAC) has been increasingly used in patients with locally advanced high-risk soft tissue sarcomas in the past decade, but definition and prognostic impact of a good histologic response (GHR) are lacking. Our aim was to investigate which histologic feature from the post-NAC surgical specimen independently correlated with metastatic relapse-free survival (MFS) in combination with clinical, radiologic, and pathologic features using a machine learning approach.

METHODS

This retrospective study included 175 consecutive patients (median age: 59 years, 75 women) with resectable disease, treated with anthracycline-based NAC between 1989 and 2015 in our sarcoma reference center, and with quantitative histopathologic analysis of the surgical specimen. The outcome of interest was the MFS. A multimodel, multivariate survival analysis was used to define GHR. The added prognostic value of GHR was investigated through the comparisons with the standard model (including histologic grade, size, and depth) and SARCULATOR nomogram using concordance indices (c-index) and Monte-Carlo cross-validation.

RESULTS

Seventy-two patients (72 of 175, 41.1%) had a metastatic relapse. Stepwise Cox regression, random survival forests, and least absolute shrinkage and selection operator–penalized Cox regression all converged toward the same definition for GHR, ie, < 5% stainable tumor cells. The five-year MFS probability was 1 (95% CI, 1 to 1) in patients with GHR versus 0.73 (95% CI, 0.65 to 0.81) in patients without GHR (log-rank P = .0122). The final prognostic model incorporating the GHR was significantly better than the standard model and SARCULATOR (average c-index in testing sets = 0.72 [95% CI, 0.61 to 0.82] v 0.57 [95% CI, 0.44 to 0.70] and 0.54 [95% CI, 0.45 to 0.64], respectively; P = .0414 and .0091).

CONCLUSION

Histologic response to NAC improves the prediction of MFS in patients with soft tissue sarcoma and represents a possible end point in future studies exploring innovative regimens in the neoadjuvant setting.
Radiation Oncology's Place in Payment Reform: ASTRO Advocates for a Place at the Table
Authors: Hubbard Anne , Mantz Constantine , Mohideen Najeeb , Hartsell William , Thaker Nikhil G. , Orio Peter , Yashar Catheryn , Kavadi Vivek , Kavanagh Brian , Adler Dave
Published: September 2021

In its current form, the Radiation Oncology Model (RO Model) prioritizes payment cuts over true value-based payment transformation. With significant modifications to the payment methodology, the reporting requirements, and recognition of the unique challenges faced by disadvantaged populations, the RO Model can protect patient access to care, preserve the physician-patient decision-making process, and ensure the delivery of high-quality, efficient radiation therapy treatment. The American Society for Radiation Oncology has spent several years advocating for a meaningful alternative payment model for radiation oncology and continues to push The Center for Medicare and Medicaid Innovation for changes to the RO Model that will recognize these key outcomes.
What Is a “Racial Health Disparity”? Five Analytic Traditions
Authors: Chowkwanyun Merlin
Published: September 2021

What exactly is a “racial health disparity”? This article explores five lenses that have been used to answer that question. It contends that racial health disparities have been presented—by researchers both within academia and outside of it—as problems of five varieties: biology, behavior, place, stress, and policy. It also argues that a sixth tradition exploring class—and its connection to race, racism, and health—has been underdeveloped. The author examines each of these conceptions of racial disparities in turn. Baked into each interpretive prism is a set of assumptions about the mechanisms that produce disparities—a story, in other words, about where racial health disparities come from. Discursive boundaries set the parameters for policy debate, determining what is and is not included in proposed solutions. How one sees racial health disparities, then, influences the strategies a society advocates—or ignores—for their elimination. The author ends by briefly discussing problems in the larger research ecosystem that dictate how racial health disparities are studied.
Queering “The Children's Movement”
Authors: Cheang Kai
Published: September 2021

This essay argues that the queer figure of the child that crops up curiously in (post–)Umbrella Movement Hong Kong is a defining political signifier for characterizing the city's youthful protesters and imagining alternative futures for Hong Kong. In many mainland Chinese media outlets, the youthfulness of the Hong Kong demonstrators is often emphasized to critique their fixation on the Western ideology of democracy. For the young resisters and their sympathizers, childishness connotes a different script of identity: it entails a narrative of temporal suspension in the face of assimilation into a Chinese homogeneity. By, for example, comparing the political star Joshua Wong to Peter Pan, who refuses to grow up, or by assigning uniform-wearing grade-school students the role of “the keepers of the Umbrella Movement,” prodemocratic cultural narratives keep alive the possibility of a political alterity that resists the neoliberal, temporal mandates of Hong Kong's government and mainland China. Theorizing that possibility in the context of temporal, queer, children's, and postcolonial studies, this essay contends that the future of resistance in Hong Kong will follow a lateral horizon, a sideways course that will put minor dissenters into new and nonheteropatriarchal relations with the existing order of the city.
COMPETÊNCIAS GERAIS REQUERIDAS AOS PROFISSIONAIS DA SOCIEDADE EM TRANSFORMAÇÃO DIGITAL: UMA PROPOSTA PARA TRABALHADORES DO SETOR INDUSTRIAL
Authors: Aires Regina Wundrack do Amaral , Freire Patricia De Sá
Published: September 2021

A partir da Terceira Revolução Industrial, quando o trabalho deixou de ser focado na tarefa, exigindo profissionais com um conjunto de competências além das competências técnicas para sua função, surgem vários estudos organizacionais e científicos apontando a lacuna sobre as competências essenciais que os profissionais devem desenvolver, bem como a importância da requalificação dos trabalhadores, pois ter profissionais com as competências certas apresenta-se sinônimo de vantagem competitiva. Com o avançar da Sociedade em Transformação Digital e sua crescente adoção de novas tecnologias, surge a questão de pesquisa: quais seriam as competências gerais que os profissionais do setor industrial da Sociedade em Transformação Digital precisam desenvolver? Neste contexto, esta pesquisa tem o objetivo de identificar as Competências Gerais requeridas aos profissionais do setor industrial da Sociedade em Transformação Digital. Para tal, foi realizada uma pesquisa teórico-empírica, utilizando-se da pesquisa bibliográfica exploratória e do método de revisão sistemática da literatura para a identificação das competências sugeridas pela ciência, pela técnica de grupo focal e uma entrevista com especialistas para a verificação de consistência dos resultados e validação das Competências Gerais propostas em campo. O resultado alcançado foi uma Matriz de Competências Gerais requeridas aos profissionais do setor industrial da Sociedade em Transformação Digital.
A PRESENÇA DA MARCA NO FACEBOOK: ESTRATÉGIA DE PUBLICAÇÃO E ENGAGEMENT DOS UTILIZADORES NA FANPAGE DA NETFLIX BRASIL
Authors: Cardoso Paulo Ribeiro , Morgado Laila Silva , Sousa Bruno Barbosa
Published: September 2021

As redes sociais constituem um canal de comunicação privilegiado que as marcas utilizam na sua relação com o consumidor. As publicações no Facebook procuram envolver os seguidores, utilizando conteúdos que possam ser mais atrativos e recorrendo a formatos como a imagem e o vídeo. Neste contexto, o presente estudo pretende apurar se as publicações contendo imagem e vídeo podem provocar mais envolvimento por parte dos utilizadores, concretamente por meio de likes, comentários e partilhas. Para isso, realizou-se uma análise da atividade da marca Netflix no Facebook durante 362 dias, correspondendo a 660 posts, tendo-se utilizado os dados disponibilizados pela aplicação Netvizz. Verificou-se que a utilização dos formatos visuais, como as imagens e os vídeos, foi escolha estratégica que resultou em um elevado envolvimento por parte dos consumidores. Com base nos resultados obtidos, são elaboradas algumas reflexões à luz da literatura científica sobre o tema; são apresentadas recomendações para profissionais, propostas e algumas orientações para futuras investigações.
DIRETRIZES PARA CONSTRUÇÃO DE TRILHAS DE APRENDIZAGEM PARA DESENVOLVIMENTO DE PROFISSIONAIS DO SETOR INDUSTRIAL DA SOCIEDADE EM TRANSFORMAÇÃO DIGITAL
Authors: Aires Regina Wundrack do Amaral , Freire Patricia De Sá
Published: September 2021

A Sociedade em Transformação Digital tem exigido um conjunto de novas competências dos profissionais de diversos setores, estimulando as organizações a buscarem novos meios de proporcionar a seus profissionais o desenvolvimento contínuo que, alinhado com seus objetivos organizacionais, possibilita a construção de valores distintivos em prol do desenvolvimento corporativo. Como facilitar o desenvolvimento de novas competências ao longo da vida profissional é um tema frequentemente abordado em pesquisas acadêmicas e buscado pelas organizações no mundo corporativo. Uma estratégia de gestão do desenvolvimento humano nas organizações se baseia na elaboração de Trilhas de Aprendizagem. Porém, há lacuna de conhecimento científico sobre as diretrizes que devem ser consideradas para o desenvolvimento de Trilhas de Aprendizagem, especificamente para a Sociedade em Transformação Digital. Com o objetivo de identificar diretrizes para construção de Trilhas de Aprendizagem para desenvolvimento de competências nos profissionais do setor industrial para a Sociedade em Transformação Digital, foi realizada uma revisão sistemática da literatura em bases de dados internacionais, que, somada a uma análise documental e bibliográfica exploratória, resultou na proposição de uma série de diretrizes a serem consideradas na construção dessas Trilhas de Aprendizagem.
Συσχέτιση μεταξύ ωτοακουστικών εκπομπών και εμβοών
Authors: Παπακώστας Κωνσταντίνος
Published: September 2021

Ο σκοπός της παρούσας μελέτης είναι να ερευνήσει, εάν συγκεκριμένες μορφέςωτοακουστικών εκπομπών μπορούν να συσχετιστούν με τις εμβοές. Η κύρια υπόθεσηπρος έλεγχο είναι ότι η ενέργεια που εκλύεται με τις ωτοακουστικές εκπομπέςμεταβάλλεται σε ορισμένες κατηγορίες εμβοών που οφείλονται σε μηχανικήδυσλειτουργία του κοχλία.Οι ωτοακουστικές εκπομπές προϊόντων παραμόρφωσης (DPOAE) είναι πάντοτεανιχνεύσιμες στο φυσιολογικό ανθρώπινο ους και αποτελέσματα έχουν δείξει ότιπαρέχουν ακρίβεια συχνότητας, πληροφορία η οποία μπορεί να χρησιμοποιηθεί γιααντικειμενική εκτίμηση της κατάστασης του κοχλία. Παρ’όλα αυτά δεν έχουνδημοσιευθεί καλά σχεδιασμένες συγκεκριμένες μελέτες ως προς τις DPOAE ατόμων μεφυσιολογική ακοή σε σχέση με τις εμβοές.Βασικό κριτήριο της ομάδας των πασχόντων ήταν η παρουσία ετεροπλεύρων ήαμφοτεροπλεύρων εμβοών χωρίς βαρηκοΐα ή άλλη ωτολογική βλάβη και ηλικία ως 50ετών. Την ομάδα αυτή αποτέλεσαν 43 άτομα. Από αυτούς, 11 ανέφεραναμφοτερόπλευρες εμβοές. Τους μάρτυρες αποτέλεσαν 50 άτομα χωρίς εμβοές ή άλληωτολογική παθολογία, αντίστοιχης ηλικίας και δημογραφικών χαρακτηριστικών.Μετρήθηκαν οι DPOAE πασχόντων και μαρτύρων σε ένα πυκνό φάσμα 26συχνοτήτων, από 708 Hz ως 6165 Hz. Ακολούθησε η εξής ανάλυση: α) σύγκρισημεταξύ 43 ώτων με εμβοές με 50 φυσιολογικά ώτα μαρτύρων έδειξε στατιστικάσημαντική διαφορά στο μέγεθος των ωτοακουστικών εκπομπών στο υψηλότερο άκροτου φάσματος συχνοτήτων, ήτοι άνω των 5000 Hz. β) σύγκριση 32 ώτων χωρίςαναφερόμενη εμβοή από την ομάδα των πασχόντων ετεροπλεύρως με 50 ώτα μαρτύρωνδεν έδειξε στατιστικά σημαντική διαφορά, αν και αυτή παρατηρήθηκε ξανά σε όλες τιςυψηλές συχνότητες. γ) εντός της ομάδας των πασχόντων από εμβοή έγινε σύγκριση τωνεκπομπών μεταξύ 43 ώτων με εμβοή και 32 ώτων χωρίς εμβοή. Δεν ανευρέθηκε σημαντική διαφορά.Συνολικά, οι μετρήσεις έδειξαν DPOAE μικρότερης έντασης στις συχνότητες άνω των3000 Hz στα ώτα με εμβοή, με ανιούσα τάση στα ώτα πασχόντων χωρίς εμβοή και τηΣελίδα | 10μεγαλύτερη ένταση στα ώτα μαρτύρων. Τα ευρήματα αυτά προσεγγίζουν ουσιωδώς τοσκοπό της παρούσας έρευνας να εντοπίσει πρώϊμες ενδείξεις για παθοφυσιολογικέςαλλαγές στον κοχλία των πασχόντων από εμβοές, δηλαδή στο στάδιο φυσιολογικήςακόμη ακοής, χρησιμοποιώντας περισσότερο ευαίσθητες μεθόδους εξέτασής του, όπωςοι ωτοακουστικές εκπομπές προϊόντων παραμόρφωσης. Ακόμη και αν οιπαθοφυσιολογικές αυτές μεταβολές δεν έχουν αιτιολογική σχέση με τις εμβοές, ημελέτη αυτή συντελεί στη διεύρυνση της γνώσης μας για τη δυναμική κατάσταση τουκοχλία επί εδάφους εμβοών.
Μελέτη της αποτελεσματικότητας και της ασφάλειας χορήγησης εκλεκτικού αναστολέα της κυκλοοξυγενάσης-2 για την αντιμετώπιση του μετεγχειρητικού πόνου σε ασθενείς που υποβάλλονται σε ολική αρθροπλαστική ισχίου και γόνατος
Authors: Δημητρίου Ευτυχία
Published: September 2021

Σκοπός: Η αντιμετώπιση του μετεγχειρητικού πόνου σε ασθενείς που προσέρχονται για ολικές αρθροπλαστικές ισχίου και γόνατος, οι οποίοι είναι στην πλειοψηφία τους ηλικιωμένοι, με πολλά συνοδά νοσήματα, αποσκοπεί στην πρόληψη των αλλαγών που θα προκαλέσει ο πόνος στο καρδιαγγειακό σύστημα, το αναπνευστικό σύστημα, την πηκτικότητα του αίματος, το γαστρεντερικό σύστημα και την κινητοποίηση του ασθενούς. Στη μελέτη μας ερευνήθηκε η επίδραση της προεγχειρητικής και μετεγχειρητικής χορήγησης παρεκοξίμπης, στον μετεγχειρητικό πόνο, στην ανάγκη για αναλγητικά φάρμακα και τις τυχόν παρενέργειες, που μπορεί να προκληθούν λόγω της χορήγησής της. Υλικό και μέθοδος: 31 Ασθενείς που ανήκαν στην κατηγορία ASA Ι έως ΙΙΙ, που προσήλθαν για ολική αρθροπλαστική ισχίου και γόνατος, τυχαιοποιήθηκαν σε δύο ομάδες: ΟΜΑΔΑ 1: Λήψη πριν την έναρξη του χειρουργείου παρεκοξίμπης 40mg (iv) σε 100ml N/S 0.9% και επανάληψη ανά 12/ωρο επί τριημέρου. ΟΜΑΔΑ 2: Λήψη πριν την έναρξη του χειρουργείου Placebo: (iv) 100mlN/S 0.9% και επανάληψη ανά 12/ωρο επί τριημέρου. Η μετεγχειρητική αναλγησία επιτεύχθηκε με τη χρήση ηλεκτρονικής αντλίας συνεχούς και κατ’ επίκληση χορήγησης διαλύματος ροπιβακαΐνης/μορφίνης. Εκτιμήθηκε η ένταση του πόνου με τη λεκτική αριθμητική κλίμακα (NRS), η κατανάλωση του αναλγητικού διαλύματος 1, 2, 12, 24 ώρες μετεγχειρητικά, οι τυχόν παρενέργειες ανά συστήματα, η ικανοποίηση των ασθενών, η ανάγκη επιπλέον φαρμακευτικής αγωγής και οι απώλειες αίματος. Αποτελέσματα: Η ομάδα που έλαβε placebo παρουσίασε σημαντικά μεγαλύτερες αναλγητικές ανάγκες σε σύγκριση με τους ασθενείς που έλαβαν παρεκοξίμπη και η ικανοποίηση των ασθενών από την αναλγησία ήταν χαμηλότερη. Επίσης οι παρενέργειες και η ανάγκη επιπλέον αγωγής λόγω αυτών στην ομάδα του placebo ήταν μεγαλύτερη. Δεν καταγράφηκε στατιστικά σημαντική διαφορά στις απώλειες αίματος. Συμπεράσματα: Η παρεκοξίμπη χορηγούμενη ως αναλγητικός παράγοντας περιεγχειρητικά, σε ασθενείς που υποβάλλονται σε ολικές αρθροπλαστικές ισχίου και γόνατος, σε συνδυασμό με επισκληρίδιο αναλγησία, μειώνει τις ανάγκες κατανάλωσης αναλγητικού, μειώνει τον μετεγχειρητικό πόνο και δεν αυξάνει τη συχνότητα εμφάνισης ανεπιθύμητων ενεργειών και τις περιεγχειρητικές απώλειες αίματος.
H προγνωστική σημασία των κυκλοφορούντων διαλυτών μορίων προσκόλλησης σε ασθενείς με μικροκυτταρικό καρκίνο πνεύμονα
Authors: Κοττέας Ηλίας
Published: September 2021

Σκοπός: Η επιθηλιακή Ε-καντερίνη, το διακυτταρικό μόριο προσκόλλησης-1 (ΙCAM-1), τοαγγειακό μόριο προσκόλλησης-1 (VCAM-1) και η ενδοθηλιακή Ε-σελεκτίνη, είναιδιαμεμβρανικές γλυκοπρωτεΐνες, που συμμετέχουν στη διαδικασία της εμβρυογένεσης, στηδιατήρηση της δομής των ιστών, στη λειτουργία του ανοσοποιητικού συστήματος, στηναγγειογένεση. Η έκφρασή τους έχει αποδεικτεί ότι κατέχει σημαντικό ρόλο στηνκαρκινογένεση και στην εξέλιξη των νεοπλασιών. Η παρούσα προοπτική μελέτη εξέτασε τηνπρογνωστική σημασία των προαναφερόμενων μορίων προσκόλλησης στον μικροκυτταρικόκαρκίνο του πνεύμονα. Μέθοδοι: Συγκεντρώθηκαν δείγματα αίματος από 50νεοδιαγνωσθέντες ασθενείς με μικροκυτταρικό καρκίνο πνεύμονα καθώς και από 27 υγιείςμάρτυρες. Tα επιπεδα μετρήθηκαν με μέθοδο ELISA. Έγινε συσχέτιση των αποτελεσμάτωνμε τα χαρακτηριστικά των ασθενών, με την επιβίωση και με τις ανταποκρίσεις των ασθενώνστην χημειοθεραπεία. Αποτελέσματα: Διαπιστώθηκε στατιστικά σημαντική αύξηση τωνεπιπέδων όλων των εξετασθέντων μορίων των ασθενών κατά την διάγνωση συγκριτικά με τιςτιμές των μαρτύρων (p<0.001). Εκτός του σταδίου και του δείκτη λειτουργικής ικανότητας, ταεπίπεδα ICAM-1 (HR: 1.005, 95% CI 1.002-1.009, p=0.041) και Ε-σελεκτίνης (HR: 1.007,95% CI 1.003-1.014, p=0.021) ήταν ανεξάρτητοι προγνωστικοί παράγοντες επιβίωσης στους12 μήνες από την διάγνωση. Επιπλέον, οι ασθενείς που είχαν μείωση των επιπέδων τουICAM-1 κατά 20% στο μέσο και κατά 19% στο τέλος της χημειθεραπείας σε σχέση με τααρχικά τους επίπεδα, εμφάνισαν αντικειμενικές ανταποκρίσεις (p=0.001 και p=0.012αντίστοιχα). Συμπεράσματα: Με τα σημαντικά αυξημένα επίπεδα όλων των εξετασθέντωνδιαλυτών μορίων στην διάγνωση των ασθενών αποδεικνύεται η συμμετοχή τους στην εξέλιξητου μικροκυτταρικού καρκίνου του πνεύμονα. Το ICAM-1 και η Ε-σελεκτίνη θα μπορούσαννα χρησιμοποιηθούν ως πρόσθετοι προγνωστικοί παράγοντες. Το ICAM-1 ενδεχομένως ναέχει ρόλο προβλεπτικού δείκτη αντικειμενικής ανταπόκρισης.