Efficacy of transcranial direct current stimulation for treating anhedonia in patients with depression: A randomized, double-blind, sham-controlled clinical trial.

BACKGROUND: Anhedonia, the core symptom of major depressive disorder (MDD), is highly prevalent in patients with depression. Anhedonia is associated with low efficacy of drug treatment, high suicide rates, and poor social function. Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technology that uses constant, low-intensity direct current to treat MDD by regulating cortical activity and neuronal excitability. However, little is known about the efficacy of tDCS for treating anhedonia in patients with depression, and even the existing results of clinical trials are conflicting. In addition, there is no consensus on what brain regions should be targeted by tDCS during the treatment of anhedonia in patients with depression. OBJECTIVE: This study aimed to evaluate the efficacy and safety of tDCS over the left dorsolateral prefrontal cortex (DLPFC) and right orbitofrontal cortex (OFC) in the improvement of anhedonia in patients with depression and finally identified suitable brain regions to be stimulated during treatment. METHODS: This randomized, double-blind, sham-controlled clinical trial recruited 70 patients with anhedonia and depressive episodes. Patients were randomly assigned to three groups according to the stimulation site: right orbitofrontal cortex (OFC), left dorsolateral prefrontal cortex (DLPFC), and sham stimulation. Each group received twelve 20-min interventions (ten as primary treatment and two for consolidation). The primary outcome was a decrease in Snaith-Hamilton Pleasure Scale (SHAPS) scores after primary treatment. Evaluations were performed at baseline, post-treatment, and 8-week follow-up. RESULTS: The depression mood of the three groups of patients at each time point was better than the baseline, but there was no significant difference in the efficacy between the groups (p>0.05). On the basis of the improvement of depression, this study found that tDCS of the DLPFC significantly improved anhedonia (p = 0.028) after primary treatment (2 weeks), and tDCS of the DLPFC and OFC significantly improved social functioning (p = 0.005) at 8-week follow-up. LIMITATIONS: The sample size of this study was small, with only about 23/24 patients in each group completing the intervention assessments; due to the impact of the COVID-19 epidemic, data analysis was limited by the lack of patients during the follow-up period. CONCLUSIONS: tDCS of the DLPFC significantly improves anhedonia in depressed patients and is thus a potential adjuvant therapy for anhedonia in these patients.

Comparison of 60-minute vs 30-minute transcranial direct current stimulation (tDCS) in major depressive disorder: Effects on depression suicidal ideation and anxiety.

We investigated whether changes through doubling the duration of each tDCS session would increase efficacy of tDCS for depression. tDCS was applied for 10 sessions, followed by two additional weekly sessions. 63 patients with MDD underwent randomization, with 22 being assigned to 60-min/d group, 25 to 30 min/d group, and 16 to sham group. HAMD-17 reductive ratios at week 2 and 4 were of no significant differences among treatment groups. 60 min group had a greater decrease in anxiety compared to 30 min group and sham group based on HAMA at 4 weeks but only in the completer analysis, not in ITT analysis.

Goals for Adherence with Low-cost Incentives (GOALS): a protocol for a randomized controlled trial evaluating the impact of small airtime incentives on ART adherence among young people living with HIV in Kampala, Uganda.

BACKGROUND: Treatment outcomes of HIV-positive individuals are threatened by low antiretroviral therapy (ART) adherence, a problem that is particularly acute among youth. Incentives are a promising tool to support ART adherence, but traditional incentive designs rewarding uniformly high levels of the desired health behavior may demotivate those with low levels of the behavior. In this study, we investigate the effectiveness of alternative approaches to target-setting for incentive eligibility using subgoals (i.e., individual-specific, interim targets leading up to the optimal target). METHODS / DESIGN: We will enroll 628 HIV-positive youth between ages 15 and 30 into a 3-year randomized controlled trial. Participants will be randomized 1:1:1:1 to a control arm or one of three intervention arms (n = 157 each) that allow them to enter a prize drawing for small incentives if their ART adherence meets the given goal. In the first arm (T1, assigned subgoal), goals will be externally assigned and adapted to their initial adherence level. In the second arm (T2, participatory subgoal), participants can set their own interim goals. In the third arm (T3, fixed goal), all participants must reach the same target goal of 90% adherence. T1 and T2 participants are required to reach 90% adherence by month 12 to participate in a larger prize drawing. The control group receives the usual standard of care. All four groups will receive weekly motivational messages; the three treatment groups will additionally receive reminders of their upcoming prize drawing. Adherence will be measured continuously throughout the intervention period using electronic devices and for 12 months post-intervention. Surveys will be conducted at baseline and every 6 months. Viral loads will be measured annually. The primary outcome is Wisepill-measured adherence and a binary measure for whether the person took at least 90% of their pills. The secondary outcome is the log-transformed viral load as a continuous measure. DISCUSSION: Our study is one of the first to apply insights about the psychology and behavioral economics of goal-setting to the design of incentives, by testing whether conditioning the eligibility threshold for incentives on subgoals (interim goals leading up to the ultimate, high goal) improves motivation and adherence more than setting a uniformly highly goal, and a comparison group. TRIAL REGISTRATION: ClinicalTrials.gov NCT05378607. Date of registration: May 18, 2022.

Influences of Spatial Accessibility and Service Capacity on the Utilization of Elderly-Care Facilities: A Case Study of the Main Urban Area of Chongqing.

With the unprecedented growth of the elderly population in China, elderly-care facilities (ECFs) are in a fast expansion process. However, limited attention has been paid to the imbalance at the actual utilization level of ECFs. This research aims to reveal the spatial inequity of ECFs and to quantitatively examine the effect of accessibility and institutional service capacity on utilization. Taking Chongqing, China, as the study area, we measured the spatial accessibility of different travel modes by the Gaussian Two-Step Floating Catchment Area (G2SFCA) method and investigated distribution differences in spatial accessibility, service capacity, and utilization of ECFs by the Dagum Gini Coefficient and its decomposition. Then, the impact of spatial accessibility and service capacity on the utilization of regional ECFs was quantified by multiscale geographically weighted regression (MGWR). The study findings can be summarized as follows. (1) Walking accessibility has the most significant impact on the utilization of ECFs and shows geographic heterogeneity. Developing a pedestrian-oriented network of pathways is essential to enhance the utilization of ECFs. (2) Accessibility by driving and bus-riding does not correlate with regional ECFs utilization, and relevant studies cannot rely on them alone for assessing the equity of ECFs. (3) In the utilization of ECFs, since the inter-regional difference is more significant than the intra-regional difference, efforts to reduce the overall imbalance should be oriented toward inter-regional variation. The study's findings will assist national policymakers in developing EFCs to enhance health indicators and quality of life for older adults by prioritizing financing for shortage areas, coordinating ECFs services, and optimizing road systems.

Prognostic prediction of subjective cognitive decline in major depressive disorder based on immune biomarkers: a prospective observational study.

OBJECTIVE: Subjective cognitive decline (SCD) is highlighted in patients with major depressive disorder (MDD), which impairs objective cognitive performance and worsens the clinical outcomes. Immune dysregulation is supposed to be the potential mechanism of cognitive impairment. However, the peripheral immune biomarkers in patients troubled with MDD and SCD are not conventionally described. METHODS: A prospective-observational study was conducted for 8 weeks. Subjective cognitive function was measured using the Chinese version of the 20-item perceived deficits questionnaire-depression (PDQ-D) and depression symptoms were evaluated with Hamilton Depression Rating Scale-17 (HDRS-17). Luminex assays were used to measure 48 immune cytokines in plasma at baseline. Integrating these results and clinicopathological features, a logistic regression model was used to develop a prognostic prediction. RESULTS: Totally, 114 patients were enrolled in this study. Among the patients who completed follow-up, 56% (N = 50) had residual subjective cognitive decline, and 44% (N = 50) did not. The plasma levels of FGF basic, INF-γ, IL-1ß, MCP-1, M-CSF and SCF were increased and the levels of IL-9, RANTES and PDGF-BB were decreased in the SCD group. Additionally, Basic FGF, IFN-γ, IL-1ß, and SCF were positively correlated and IL-9, RANTES, and PDGF-BB were negatively correlated with the PDQ-D scores after treatment. Notably, combinations of cytokines (SCF and PDGF-BB) and PDQ-D scores at baseline showed good performance (The area under the receiver operating characteristic curve = 0.818) in the prediction of subjective cognitive decline. CONCLUSION: A prognostic model based on protein concentrations of SCF, PDGF-BB, and scores of PDQ-D showed considerable accuracy in predicting residual subjective cognitive decline in depression.

SPECT/CT imaging features of cystic degeneration of the talus and their relation to pathological findings.

BACKGROUND: Osteochondral lesions of the talus (OLTs) are a common orthopedic condition. The image presentation is very similar to that of ischemic necrosis of the talus complicated by a talar neck fracture, but the two are very different lesions. When abnormalities in bone density (or signal) of the talar body (apex of the fornix) with concomitant bone defects and cystic changes are found on X-ray, computed tomography (CT), or magnetic resonance imaging, it is important to accurately determine the nature of the lesion and make a correct diagnosis for the treatment and prognosis of the patient. The purpose of this study was to explore the imaging features of three-phase single-photon emission computed tomography (SPECT)/CT images of cystic lesions of the talus. METHODS: A total of 189 patients with chronic pain in the ankle joint suspected to be caused by cystic degeneration of the talus were enrolled. All patients underwent 99mTc-methyl diphosphonate (99mTc-MDP) three-phase SPECT/CT bone imaging and delayed scans in our hospital. The location, range of involvement, classification, CT value, and radioactivity uptake of the sclerotic areas of cystic lesions on the talus, and the continuity of the articular surface, were recorded. All recorded parameters were analyzed in comparison with pathological results. RESULTS: Eighty-three percent (157/189) of the talar cysts were located on the medial fornix, largely involving the anterior middle part (43.27%), with larger cysts involving the posterior part (9.6%). Sixty-three percent (119/189) of the patients had type I lesions and 37% (70/189) had type II lesions. The articular surface of the medial dome of the talus was intact in all patients, but the subchondral bony articular surface was rough in 88% (166/189) of patients. The coincidence rate for the location, type, and range of involvement of cystic lesions with the pathological results was 87.83% (166/189). The mean CT value of the cystic lesions was 45 ± 15 HU (30-60 HU). The percentages of pathological chondrogenesis in high CT value ≥ 50 HU (19/70) and low CT value < 50 HU (51/70) groups were 89.47% (17/19) and 29.14% (15/51) (χ2 = 20.12, p < 0.001), respectively. The target/background ratio (T/B ratio) of the radioactivity-uptake area of the talus vault was 2.0 ± 0.5 (1.5-2.5). The percentages of pathological new trabecular bone in those with a T/B ratio ≥ 2.0 (157/189) and T/B ratio < 2.0 (32/189) were 82.80% (130/157) and 25.00% (8/32; χ2 = 45.08, p < 0.001), respectively. CONCLUSIONS: Three-phase bone imaging could identify damage of the talus caused by cystic degeneration, while delayed SPECT/CT images showed advantages for displaying bone microstructure, blood supplement, and bone metabolism when examining the location, range of involvement, classification, and repair of cystic lesions of the talus.

Ketamine May Exert Rapid Antidepressant Effects Through Modulation of Neuroplasticity, Autophagy, and Ferroptosis in the Habenular Nucleus.

Major depressive disorder is a burdensome condition with few treatment options, and traditional antidepressants are characterized by slow onset. Sub-anesthetic ketamine has rapid-onset effects for the treatment of major depressive disorder (MDD), the mechanisms of which remain elusive. In this study, we explored whether neuroplasticity, autophagy, and ferroptosis in the habenular nucleus are involved in the rapid antidepressant process of ketamine. The results showed that Chronic Restraint Stress (CRS) treated rats exhibited decreased neuroplasticity, inhibition of autophagy, and enhanced ferroptosis. Depression-like symptoms were significantly improved after ketamine treatment in CRS rats, with changes in physiological parameters. Ketamine-treated CRS rats showed a significant improvement in habenular nuclear neuroplasticity. Electron microscopy observed that ketamine triggered autophagy, with increased levels of autophagy-related proteins. Ferroptosis was inhibited by ketamine by electron microscopy, with increased FTH1 and GPX4 levels and decreased Tfr1 levels. In conclusion, our findings demonstrate that ketamine may exert rapid antidepressant effects by improving neuroplasticity, activating autophagy, and inhibiting ferroptosis in the nuclear complex.

Ketamine induces rapid antidepressant effects via the autophagy-NLRP3 inflammasome pathway.

BACKGROUND: Sub-anesthetic ketamine has rapid-onset effects for the treatment of major depressive disorder (MDD). However, the mechanism underlying ketamine's antidepressant properties remains unclear. Recent studies have reported an interrelationship between autophagy and the inflammasome, both of which are involved in the pathophysiology of MDD. In this study, we assess whether ketamine exerts its antidepressant effects via an association with the autophagy-NLRP3 inflammasome pathway. METHODS: We established a depressive-like rat model by treating Wistar Kyoto rats with chronic restraint stress (CRS) for 28 days. Microglial cells from newborn Sprague-Dawley rats were used for in vitro experiments. RESULTS: We found sub-anesthetic ketamine treatment reversed depressive-like behavior in CRS rats. Ketamine triggered autophagy in the microglia of prefrontal cortex (PFC) and (hippocampus) HPC, with increased levels of LC3B, decreased levels of p62 protein, and elevated autophagosomes both in vivo and in vitro. Moreover, NLRP3 inflammasome activation was also inhibited by ketamine, with reduced expression of NLRP3-ASC-CASP1 assembly and decreased IL-1ß levels in cerebrospinal fluid (CSF) as well as in the serum. Increased BDNF levels and synaptophysin levels were detected in the ketamine-treated group. The rapid anti-depressive effects, elevation of autophagy, reduction in NLRP3, and neuroplasticity-related factors induced by ketamine could be significantly blocked by the autophagy inhibitor Baf A1 (0.1 mg/kg). CONCLUSIONS: Our findings demonstrate that sub-anesthetic doses of ketamine exert their antidepressant-like effects by inhibiting inflammation and initiating neuroprotection via autophagy activation. These data might help expand future investigations on the antidepressant properties of ketamine.

Short- and Long-Term Influences of Benzodiazepine and Z-Drug Use in Patients with Bipolar Disorder Combined Sleep Disturbance during Affective Period: A Nine-Month Follow-Up Analysis.

Background: Sleep disturbances and benzodiazepine (BZD)/Z-drug use are common in patients with bipolar disorder (BD). Objective: To investigate the short- and long-term effects of BZD/Z-drug use during acute affective episode. Methods: Participants diagnosed with BD as well as sleep disturbance chose BZDs/Z-drugs or not at will. Manic and depressive symptoms were assessed by Mental Disorders Questionnaire (MDQ) and Quick Inventory of Depressive Symptoms (QIDS) as self-reporting surveys. The participants were assessed by trained evaluators at baseline and months 1, 3, 6, and 9. Results: 61 patients with BD combined sleep disturbances were studied. At baseline, patients who used BZDs/Z-drugs had more amount of mood stabilizers (p = 0.038), other psychotropic medications (p = 0.040), and more risk of suicide attempt (p = 0.019). The BZD/Z-drug group had a significantly higher QIDS reductive ratio as compared with the no BZD/Z-drug group at month 1; no significant differences in the variability of MDQ, QIDS reductive ratio, or recurrence rate were found between these two groups at baseline, month 1, month 3, month 6, or month 9. Conclusions: During acute affective episode, patients with BD combined sleep disturbance who took BZDs/Z-drugs tended to use more amount of mood stabilizers. Polytherapy of BZDs/Z-drugs or other psychiatric drugs could increase suicide attempt during an acute affective episode. BZD/Z-drug use, however, had a significant effect on helping depressive symptoms alleviate during affective period.

Difference in the regulation of biological rhythm symptoms of Major depressive disorder between escitalopram and mirtazapine.

BACKGROUND: Biological rhythm plays an important role in major depressive disorder (MDD). The efficacy of antidepressant in biological rhythm remains unclear. This study is designed to explore the efficiency of escitalopram and mirtazapine in improving circadian rhythm, diurnal mood variation(DMV) and daily activity in MDD patients. METHODS: Four-hundred and fifty participants diagnosed with MDD were randomized to receive treatment with escitalopram (TWE), treatment with mirtazapine (TWM) or treatment as usual (TAU). Biological rhythm symptoms were assessed by relevant biological subscale in the Hamilton depression scale (HAMD) and the quick inventory of depressive symptomatology self-report (QIDS). The participants were assessed by trained evaluators at baseline and week 2, 4, 6 and 8. RESULTS: The differences of HAMD score among TWE(58%, 69%, 72%), TWM(56%, 64%, 76%) and TAU(49%, 57%, 68%) were significant(P<0.05). But the differences were significant only in patients without DMV; (2) Sleep rhythm items (difficulty falling asleep and early-wake) were significantly improved in TWM (P <0 .05) for both HAMD and QIDS. Decreased appetite and weight were significantly improved in TWM (P<0 .05) for both scales. (3) For daily activity-related items, feeling slowed down and concentration were significantly improved in TWE. And the retardation was significantly improved in TWE and in TWM. CONCLUSIONS: Both escitalopram and mirtazapine have superior anti-depressive effect, especially for MDD patients without DMV. Escitalopram was significantly more effective in daily activity, feeling slowed down and concentration difficulty, while mirtazapine was significantly more effective in improving sleep, appetite and weight of MDD.

Sexual orientation and characteristics of sexual behaviors among 200 HIV positive male college students in Beijing / 中国学校卫生

Objective@#To understand sexual orientation and characteristics of sexual behaviors related with HIV infection among HIV positive male college students in Beijing and to provide suggestions for development of sexual health education and HIV prevention strategy for student population.@*Methods@#HIV positive male college students diagnosed from 2016 to June 30, 2019 in Beijing were recruited. Questionnaire was used to retrospectively investigate sexual orientation and characteristics of sexual behaviors before HIV infection. Behaviors related to HIV infection were compared between absolutely homosexual and others sexual orientation.@*Results@#The average age of male students firstly identified to be HIV positive was (22.18±2.70) years old, 61.5%(123) of them were undergraduate, 69.5%(139) were not registered permanent residency in Beijing, 38.5%(77) of their interviewed sexual partners were from online chat and 83.0%(166) had homosexual behaviors. Sexual orientation score analysis showed that 50.0% of the participants self identified as exclusively homosexual. Compared with other sexual oriental group, exclusively homosexual group had lower mean age of their HIV infection firstly identified（ t =2.77， P =0.01）, higher rate of Rush use, firstly insertive sexual behavior with male, firstly insertive sexual behavior before 18 years old, sexual partners more than three persons, having regular partners, nonpersistent use of condom, being diagnosed of sexual transmitted disease and the frequency of homosexual behaviors more than 1 time per month （ χ 2=5.15,28.06,4.16,5.34,5.89,7.39,6.68, P <0.05）. Rush users had higher rate of STD diagnosis than non users in exclusively homosexual group ( χ 2=6.26， P =0.01).@*Conclusion@#Risky sexual behaviors associated with HIV infection were higher in exclusively homosexual group then other sexual orientation groups among HIV positive male college students. Family and school should concern with sexual health education byreinforcing health education via network media to improve college students’ awarenees on HIV/AIDS.

Nudging Handwashing among Primary School Students in the Philippines: Evidence from a Cluster Randomized Trial.

Handwashing is key to preventing the transmission of various infectious diseases of which school-aged children are particularly susceptible. Traditional, information-messaging campaigns may increase handwashing awareness but have had limited success in promoting behavior change. Behavioral economics "nudges," which explicitly target the knowledge-behavior gap, is a promising alternative. We evaluate the impact of school-based nudges in the first fully powered cluster randomized controlled trial in the Philippines. Out of our sample of 132 eligible schools, we randomly assigned half to receive nudges, including contextual cues (painted footpath from toilet to handwashing station) and visible reminders (posters and eye sticker), and half to the control group. Four months after implementation, we measured handwashing with soap (HWWS) after toilet use among grades 1-6 students using direct observation and compared this outcome between treatment and control schools. We also assessed whether nudges increased soap availability. The intervention increased HWWS rates by 17.3% points (pp), [95% CI: 4.2, 30.4] in treatment schools from the control group mean of 11.7%. The effect size was comparable across gender and age groups. Access to functioning handwashing facilities with soap increased by 36% (+20.2 pp, 95% CI: 10.9, 29.4). Mediation analysis suggests the program simultaneously nudged students to wash hands with soap in classrooms that already had soap, and nudged teachers to provide soap where it was not already available. These findings demonstrate that behavioral nudges costing less than $70 per school can lead to significant increases in HWWS among students 4 months post-intervention.

A novel classification for medial malleolar fracture based on the 3-D reconstruction CT.

BACKGROUND: Fracture of the medial malleolus is one of the most frequent injuries treated surgically; however, the classification of the fracture has not attracted much attention and a good classification system is still lacking. METHODS: Consecutive cases of medial malleolus fractures were prospectively enrolled. Based on the 3-D reconstruction CT morphology and centered on the posterior colliculus of the medial malleolus, we classified the fractures into 4 types: type 1 with no involvement of the posterior colliculus, type 2 with partial involvement of posterior colliculus, type 3 with the entire involvement of posterior colliculus, and type 4 with the fracture line 4 vertically extended from the intercollicular groove to the comminuted fracture of the posterior malleolus. Statistical analyses were performed to evaluate the clinical significance of the classification. RESULTS: There were 273 cases prospectively enrolled. The distribution of the cases was type 1 of 12.1%, type 2 of 41.0%, type 3 of 30.0%, and type 4 of 16.8%. Statistics showed that the new classification had significant associations but did not totally depend on the classical ankle fracture classifications. Results showed that the new classification had implications in the severity of ankle fractures. From type 1 to type 4, the ankle joint was more and more unstable. Furthermore, comminuted medial malleolar fractures could be subdivided, and the new classification could provide useful information for surgical decision-making. CONCLUSIONS: The novel classification was a useful system to describe the 3-D geometry of the fractured medial malleolus.

Rush use and related factors among HIV positive young male students in Beijing / 中国学校卫生

Objective@#This study investigated the use of rush and related factors among HIV positive male students in Beijing, and provided suggestions for education and intervention.@*Methods@#Data on HIV positive male students was collected from 2017 to June 30, 2020 in Beijing and analyzed in SPSS 20.0.@*Results@#A total of 200 valid questionnaires were collected. The mean age at HIV diagnosis was (22.18±2.70) years. The rate of using rush was 46.00%. The proportion with homosexual behavior before infection was 92.00%. The results of multivariate analysis showed that meeting sexual partners through the Internet( OR=3.84, 95%CI =1.65-8.96), drinking alcohol( OR=3.26, 95%CI =1.51-7.02), group homosexual behavior( OR=4.84, 95%CI =1.71-13.71), and STD diagnosis ( OR=0.23, 95%CI =1.02-4.87) were associated with the use of rush before infection.@*Conclusion@#The rate of rush use was higher among male students infected with HIV. Government regulation could be strengthened and drug abuse could be prevented through better health education for students.

The effect and clinical significance of FN1 expression on biological functions of gastric cancer cells.

Fibronectin 1 (FN1) is a glycoprotein molecule widely distributed in cell structures such as smooth muscle cell layer, vascular cell membrane and nerve cell layer. It participates in cell adhesion, migration and movement of various cells. In recent years, FN1 has been shown to play an important role in the regulation of various malignant tumors such as lung cancer, colorectal cancer, and ovarian cancer. However, its regulation and mechanism of action in gastric cancer have been rarely reported, and these are also associated with some controversy. The aim of this study was to investigate the clinical significance of FN1 in gastric cancer, to study the effects of FN1 on proliferation, apoptosis, migration and invasion of GC cells, and the mechanisms involved. The expression of FN1 in gastric cancer tissues was determined using immunohistochemistry staining. The comparative expression levels of FN1 were assayed with RT-PCR and Western blotting. The correlation amongst FN1 expression, clinicopathological parameters and prognosis of gastric cancer patients was determined. Cell transfection was used to silenceFN1 expression in gastric cancer cells. Plate cloning and CCK-8 assays were used to determine cell proliferation, while apoptosis was assayed with flow cytometry. Cell migration and invasion was measured with transwell assay. The expressions of EMT-related proteins were assayed using western blotting. The results showed that FN1 was upregulated in GC tissues and cell lines, and its expression level was closely related to tumor invasion, TNM stage, lymph node metastasis and survival. Inhibition of FN1 expression significantly reduced proliferation, migration, invasion and EMT processes of GC cells, and enhanced cell apoptosis. These results confirm that FN1 is up-regulated in GC, thereby functioning as an oncogenic gene. The high expression of FN1 might affect the clinicopathological parameters and prognosis of gastric cancer patients.

Exosomal lncRNA DOCK9-AS2 derived from cancer stem cell-like cells activated Wnt/ß-catenin pathway to aggravate stemness, proliferation, migration, and invasion in papillary thyroid carcinoma.

Exosomal long non-coding RNAs (lncRNAs) are crucial factors that mediate the extracellular communication in tumor microenvironment. DOCK9 antisense RNA2 (DOCK9-AS2) is an exosomal lncRNA which has not been investigated in papillary thyroid carcinoma (PTC). Based on the result of differentially expressed lncRNAs in PTC via bioinformatics databases, we discovered that DOCK9-AS2 was upregulated in PTC, and presented elevation in plasma exosomes of PTC patients. Functionally, DOCK9-AS2 knockdown reduced proliferation, migration, invasion, epithelial-to-mesenchymal (EMT) and stemness in PTC cells. PTC-CSCs transmitted exosomal DOCK9-AS2 to improve stemness of PTC cells. Mechanistically, DOCK9-AS2 interacted with SP1 to induce catenin beta 1 (CTNNB1) transcription and sponged microRNA-1972 (miR-1972) to upregulate CTNNB1, thereby activating Wnt/ß-catenin pathway in PTC cells. In conclusion, PTC-CSCs-derived exosomal lncRNA DOCK9-AS2 activated Wnt/ß-catenin pathway to aggravate PTC progression, indicating that DOCK9-AS2 was a potential target for therapies in PTC.

Chinese Consensus on Insertional Achilles Tendinopathy.

BACKGROUND: Insertional Achilles tendinopathy (IAT) is a common finding in the clinic. However, consensus on its mechanism, pathological process, diagnosis, treatment, and rehabilitation is lacking. Thus, the Chinese Society of Sports Medicine organized and invited experts representing the fields of ankle disease and tendinopathy to jointly develop an expert consensus on IAT. STUDY DESIGN: A consensus statement of the Chinese Society of Sports Medicine. METHODS: A total of 34 experts in the field of sports medicine and orthopaedics were invited to participate in the compilation of a consensus statement regarding IAT. Consensus was achieved according to the Delphi method. First, 10 working groups composed of 34 experts were established to compile draft statements about clinical problems related to IAT by reviewing and analyzing the available literature. An expert consensus meeting to discuss drafts was then arranged. Each statement was individually presented and discussed, followed by a secret vote. Consensus was reached when more than 50% of the experts voted in its favor. The strength of the proposed recommendation was classified based on the proportion of favorable votes: consensus, 51% to 74%; strong consensus, 75% to 99%; unanimity, 100%. RESULTS: Of the 10 expert consensus statements on the clinical diagnosis and treatment of IAT, there was strong consensus for 8 statements and unanimity for 2 statements. CONCLUSION: This expert consensus focused on the concepts, causes, pathological process, clinical diagnosis, and treatment of IAT. Accepted recommendations in these areas which will assist clinicians in carrying out standardized management of related diseases.

Supporting Adolescents to Adhere (SATA): Lessons learned from an intervention to achieve medication adherence targets among youth living with HIV in Uganda.

INTRODUCTION: Youth in Uganda are disproportionately impacted by HIV and report significant barriers to ART adherence. We asked participants how fixed versus flexible adherence target setting for incentive interventions, in combination with other support systems, could help HIV-positive youth in Uganda reach medication adherence targets. METHODS: Four focus groups conducted in Luganda were audiotaped, transcribed, and translated into English; the transcriptions were then coded using Dedoose software. Two members of the research team read the text and identified the basic topics covered. A codebook was developed that detailed inclusion and exclusion criteria for each topic area, as well as typical entries for each code. A directed content analysis was used to identify key themes. RESULTS: Several themes were common across groups. Participants consistently maintained that they preferred to set their own adherence targets. But regardless of how adherence targets were assigned, participants noted that missing their target was disappointing. They commented positively on the use of Medication Event Monitoring System (MEMS) caps, noting that knowing their adherence information was being tracked often encouraged them to take their medications. Participants reported that receiving text messages further motivated them to take their medications; however, on occasions when they reported not doing well, they wanted intensive follow-up by staff. Participants said that the prize drawing alone did not motivate their ART adherence and that receiving 'zero' in the drawing was disheartening. CONCLUSION: We found that participants preferred to set their own adherence targets and that doing so increased a sense of ownership in achieving them. All participants enjoyed using MEMS caps and expressed disappointment at needing to return the device at the study's completion. Participants noted that text message reminders may be a useful way to help patients stay motivated between clinic visits; however, ongoing engagement and support are needed from providers and counselors. Finally, our participants stressed the importance of including incentives with a small, positive value rather than 0 when designing the lowest prize.

Treatment of the surgical neck fracture of the humerus with a novel external fixator in the elderly with osteoporosis: biomechanical analysis.

BACKGROUND: No consensus exists on the treatment of proximal humerus fractures, especially in the elderly patients with osteoporosis. This study was aimed to evaluate the biomechanical characteristics of a novel external fixator in treating two-part surgical neck fracture of the proximal humerus in the elderly patients with osteoporosis. METHODS: Sixteen female elderly humeral shaft specimens with osteoporosis were randomized into 2 groups. Models with the surgical neck two-part fracture of the proximal humerus were built, in which a novel external fixator (test group) and a clover plate (control group) were applied separately. In the test group, the fracture was firstly fixed with intersection pinning using 3 Schanz pins (3.5 mm), followed by the novel external fixation frame. In the control group, a clover plate and 6 cortical bone screws were applied. Biomechanical testing of the specimens was performed to assess the resistance to load bearing and torsional stress. The parameters of the two groups were compared using independent t-test. RESULTS: Ultimate bearing capacity and load bearing at different parts with the humerus rotation were higher (P < 0.05) in the external fixator group (145.16 ± 17.42 N and 140 N respectively) than those in the plate group (120.21 ± 13.15 N and 69.63 ± 25.16-90.78 ± 17.18 N respectively). As for resistance to torsional stress, plate's torque fluctuated between 1 Nm and 5 Nm, while the external fixator's torque values were more evenly (P < 0.01) distributed with the fluctuation within 1 Nm. CONCLUSIONS: In the fixation of two-part humeral fracture in elderly patients with osteoporosis, the new external fixator seemed to be superior to plate fixation in load bearing and resistance to torsional stress.

Text Messaging for Improving Antiretroviral Therapy Adherence: No Effects After 1 Year in a Randomized Controlled Trial Among Adolescents and Young Adults.

OBJECTIVES: To assess the effectiveness of Short Message Service (SMS) reminder messages on antiretroviral and cotrimoxazole prophylaxis adherence among HIV-positive youths as well as the relative effectiveness of SMS with and without a response option. METHODS: Eligible HIV-positive patients aged 15 to 22 years at 2 HIV clinics in Kampala, Uganda, participated in a year-long parallel individual-randomized controlled trial and were assigned in a 1-to-1-to-1 ratio to a weekly SMS message group, weekly SMS message with response option group, or a usual-care control group. RESULTS: We enrolled 332 participants. Electronically measured mean adherence was 67% in the control group, 64% in the 1-way SMS group (95% confidence interval [CI] = 0.77, 1.14), and 61% in the 2-way SMS group (95% CI = 0.75, 1.12) in an intent-to-treat analysis. Results for secondary outcomes and complete-case analysis were similarly statistically insignificant across groups. CONCLUSIONS: Despite previous evidence that interventions using SMS reminders can promote antiretroviral therapy adherence, this study shows that they are not always effective in achieving behavior change. More research is needed to find out for whom, and under what conditions, they can be beneficial. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00830622.