Do measures of social support and social distress share general factors associated with suicidal ideation and attempts?

INTRODUCTION: Aspects of social relationships have variably been associated with suicidal ideation (SI) and suicide attempts (SAs). This study assessed whether social support and social distress measures have general factors versus measure-specific factors that are associated with suicide risk. METHODS: Adults (N = 455, 60.0% female), admitted to psychiatric inpatient units following a recent suicide attempt or active SI, completed assessments of social support (emotional support, instrumental support, friendship, perceived support from significant others, friends, family) and social distress (loneliness, perceived rejection, perceived burdensomeness, thwarted belongingness). Bifactor modeling examined general and specific factors of social support and distress in relation to SI (week prior to hospitalization, via the Beck Scale for SI) and SAs (past 30 days, via the Columbia Suicide Severity Rating Scale). RESULTS: SI was significantly associated with the general social support (B = -1.51), the general social distress (B = 1.67), and the specific perceived burdensomeness (B = 1.57) factors. SAs were significantly associated with the specific Perceived Rejection (OR = 1.05) and Thwarted Belongingness (OR = 0.91) factors. CONCLUSION: General social support and social distress were associated with SI but not recent SAs. Specific social distress factors were also related to SI and SAs controlling for general social distress, suggesting areas for future interventions.

Depression symptom outcomes and re-engagement among VA patients who discontinue care while symptomatic.

OBJECTIVE: Evaluate outcomes of Veterans who discontinued treatment with at least moderate ongoing depressive symptoms. METHOD: Veterans with elevated depression symptoms from 29 Department of Veterans Affairs facilities completed baseline surveys and follow-up assessments for one year. Analyses examined rates and predictors of treatment discontinuation, treatment re-engagement, and subsequent symptoms among patients who remained out of care. RESULTS: A total of 242 (17.8%; n = 1359) participants discontinued treatment while symptomatic, with Black participants, participants with less severe depression, and participants receiving only psychotherapy (versus combined psychotherapy and antidepressant medications) discontinuing at higher rates. Among all participants who discontinued treatment (n = 445), 45.8% re-engaged within the following six months with participants receiving combined treatment re-engaging at higher rates. Of participants who discontinued while symptomatic within the first 6 months of the study and did not return to care (n = 112), 68.8% remained symptomatic at 12 months. Lower baseline treatment expectancy and greater depression symptom severity were associated with remaining symptomatic while untreated. CONCLUSIONS: Black race, lower symptom severity, and treatment modality may help identify patients at higher risk for discontinuing care while symptomatic, whereas patients with lower treatment expectations may be at greater risk for remaining out of care despite continuing symptoms.

Search for the Pair Production of Dark Particles X with K_{L}

We present the first search for the pair production of dark particles X via K_{L}^{0}→XX with X decaying into two photons using the data collected by the KOTO experiment. No signal was observed in the mass range of 40-110 MeV/c^{2} and 210-240 MeV/c^{2}. This sets upper limits on the branching fractions as B(K_{L}^{0}→XX)<(1-4)×10^{-7} and B(K_{L}^{0}→XX)<(1-2)×10^{-6} at the 90% confidence level for the two mass regions, respectively.

Implementation of Bronchoscopic Lung Volume Reduction Using One-Way Endobronchial Valves: A Retrospective Single-Centre Cohort Study.

BACKGROUND: Bronchoscopic lung volume reduction (BLVR) using 1-way endobronchial valves (EBV) has become a guideline treatment in patients with advanced emphysema. Evidence from this minimally invasive treatment derives mainly from well-designed controlled trials conducted in high-volume specialized intervention centres. Little is known about real-life outcome data in hospitals setting up this novel treatment and which favourable conditions are required for a continuous successful program. OBJECTIVES: In this study, we aim to evaluate the eligibility rate for BLVR and whether the implementation of BLVR in our academic hospital is feasible and yields clinically significant outcomes. METHOD: A retrospective evaluation of patients treated with EBV between January 2016 and August 2019 was conducted. COPD assessment test (CAT), forced expiratory volume in 1 s (FEV1), residual volume (RV), and 6-min walking test (6MWT) were measured at baseline and 3 months after intervention. Paired sample t tests were performed to compare means before and after intervention. RESULTS: Of 350 subjects screened, 283 (81%) were not suitable for intervention mostly due to lack of a target lobe. The remaining 67 subjects (19%) underwent bronchoscopic assessment, and if suitable, valves were placed in the same session. In total, 55 subjects (16%) were treated with EBV of which 10 did not have complete follow-up: 6 subjects had their valves removed because of severe pneumothorax (n = 2) or lack of benefit (n = 4) and the remaining 4 had missing follow-up data. Finally, 45 patients had complete follow-up at 3 months and showed an average change ± SD in CAT -4 ± 6 points, FEV1 +190 ± 140 mL, RV -770 ± 790 mL, and +37 ± 65 m on the 6MWT (all p < 0.001). After 1-year follow-up, 34 (76%) subjects had their EBV in situ. CONCLUSION: Implementing BLVR with EBV is feasible and effective. Only 16% of screened patients were eligible, indicating that this intervention is only applicable in a small subset of highly selected subjects with advanced emphysema, and therefore a high volume of COPD patients is essential for a sustainable BLVR program.

Dual-Energy Computed Tomography Compared to Lung Perfusion Scintigraphy to Assess Pulmonary Perfusion in Patients Screened for Endoscopic Lung Volume Reduction.

BACKGROUND: Endoscopic lung volume reduction (ELVR) using one-way endobronchial valves is a technique to reduce hyperinflation in patients with severe emphysema by inducing collapse of a severely destroyed pulmonary lobe. Patient selection is mainly based on evaluation of emphysema severity on high-resolution computed tomography and evaluation of lung perfusion with perfusion scintigraphy. Dual-energy contrast-enhanced CT scans may be useful for perfusion assessment in emphysema but has not been compared against perfusion scintigraphy. AIMS: The aim of the study was to compare perfusion distribution assessed with dual-energy contrast-enhanced computed tomography and perfusion scintigraphy. MATERIAL AND METHODS: Forty consecutive patients with severe emphysema, who were screened for ELVR, were included. Perfusion was assessed with 99mTc perfusion scintigraphy and using the iodine map calculated from the dual-energy contrast-enhanced CT scans. Perfusion distribution was calculated as usually for the upper, middle, and lower thirds of both lungs with the planar technique and the iodine overlay. RESULTS: Perfusion distribution between the right and left lung showed good correlation (r = 0.8). The limits of agreement of the mean absolute difference in percentage perfusion per region of interest were 0.75-5.6%. The upper lobes showed more severe perfusion reduction than the lower lobes. Mean difference in measured pulmonary perfusion ranged from -2.8% to 2.3%. Lower limit of agreement ranged from -8.9% to 4.6% and upper limit was 3.3-10.0%. CONCLUSION: Quantification of perfusion distribution using planar 99mTc perfusion scintigraphy and iodine overlays calculated from dual-energy contrast-enhanced CTs correlates well with acceptable variability.

Study of the K_{L}→π

The rare decay K_{L}→π^{0}νν[over ¯] was studied with the dataset taken at the J-PARC KOTO experiment in 2016, 2017, and 2018. With a single event sensitivity of (7.20±0.05_{stat}±0.66_{syst})×10^{-10}, three candidate events were observed in the signal region. After unveiling them, contaminations from K^{±} and scattered K_{L} decays were studied, and the total number of background events was estimated to be 1.22±0.26. We conclude that the number of observed events is statistically consistent with the background expectation. For this dataset, we set an upper limit of 4.9×10^{-9} on the branching fraction of K_{L}→π^{0}νν[over ¯] at the 90% confidence level.

Serial measurements in COVID-19-induced acute respiratory disease to unravel heterogeneity of the disease course: design of the Maastricht Intensive Care COVID cohort (MaastrICCht).

INTRODUCTION: The course of the disease in SARS-CoV-2 infection in mechanically ventilated patients is unknown. To unravel the clinical heterogeneity of the SARS-CoV-2 infection in these patients, we designed the prospective observational Maastricht Intensive Care COVID cohort (MaastrICCht). We incorporated serial measurements that harbour aetiological, diagnostic and predictive information. The study aims to investigate the heterogeneity of the natural course of critically ill patients with a SARS-CoV-2 infection. METHODS AND ANALYSIS: Mechanically ventilated patients admitted to the intensive care with a SARS-CoV-2 infection will be included. We will collect clinical variables, vital parameters, laboratory variables, mechanical ventilator settings, chest electrical impedance tomography, ECGs, echocardiography as well as other imaging modalities to assess heterogeneity of the course of a SARS-CoV-2 infection in critically ill patients. The MaastrICCht is also designed to foster various other studies and registries and intends to create an open-source database for investigators. Therefore, a major part of the data collection is aligned with an existing national intensive care data registry and two international COVID-19 data collection initiatives. Additionally, we create a flexible design, so that additional measures can be added during the ongoing study based on new knowledge obtained from the rapidly growing body of evidence. The spread of the COVID-19 pandemic requires the swift implementation of observational research to unravel heterogeneity of the natural course of the disease of SARS-CoV-2 infection in mechanically ventilated patients. Our study design is expected to enhance aetiological, diagnostic and prognostic understanding of the disease. This paper describes the design of the MaastrICCht. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the medical ethics committee (Medisch Ethische Toetsingscommissie 2020-1565/3 00 523) of the Maastricht University Medical Centre+ (Maastricht UMC+), which will be performed based on the Declaration of Helsinki. During the pandemic, the board of directors of Maastricht UMC+ adopted a policy to inform patients and ask their consent to use the collected data and to store serum samples for COVID-19 research purposes. All study documentation will be stored securely for fifteen years after recruitment of the last patient. The results will be published in peer-reviewed academic journals, with a preference for open access journals, while particularly considering deposition of the manuscripts on a preprint server early. TRIAL REGISTRATION NUMBER: The Netherlands Trial Register (NL8613).

Energy transfer from adipocytes to cancer cells in breast cancer.

Limitations of the current therapeutic approach have raised the need for a novel therapeutic agent in breast cancer. Recently, interest in drugs targeting the tumor microenvironment (TME) had drawn attention in the treatment of breast cancer. Furthermore, recent studies have suggested the role of adipocytes, which are part of the TME, in tumor initiation, growth, and metastasis. In this study, we investigated the metabolic interaction between adipocytes and breast cancer cells and its potential as a new therapeutic target in breast cancer. Breast cancer cell lines and human breast cancer tissue samples were evaluated. Compared to cancer cells cultured alone, or the control group, those co-cultured with adipocytes showed lipid transfer from adipocytes to cancer cells and it was different according to the molecular subtype of breast cancer. Breast cancer cells affected the lipolysis of adipocytes and adipocytes affected the ß-oxidation of breast cancer cells. The key molecule of the process was fatty acid binding protein 4 (FABP4), which is combined with free fatty acid (FFA) and supports its migration to cancer cells. When FABP4 was suppressed, lipid transfer between adipocytes and cancer cells, lipolysis of adipocytes, and ß-oxidation of breast cancer cells were reduced. Furthermore, the expression of lipid metabolism-related proteins and lipolysis-related proteins in breast cancer with adipose stroma showed significantly different expression according to the region of breast cancer tissue. Taken together, we demonstrated the metabolic interaction between adipocytes and breast cancer cells. Breast cancer cells increase the lipolysis in adipocytes and produce a fatty acid, and fatty acid enters into cancer cells. Also, adipocytes contribute to the survival and growth of cancer cells through increased mitochondrial ß-oxidation by using fatty acid from adipocytes. The key molecule of the process is FABP4 and when FABP4 is suppressed, the metabolic interaction is reduced, suggesting its role as a potential therapeutic target.

Therapeutic effects of Artemisia scoparia Waldst. et Kitaib in a murine model of atopic dermatitis.

BACKGROUND: Artemisia scoparia Waldst. et Kitaib (AS) (Oriental wormwood, known as Bissuk in Korea) is a plant used in cosmetic and pharmaceutical treatments. However, the effect of AS on atopic dermatitis (AD) has not been described. AIM: To examine the inhibitory effect of AS on AD using a murine model. METHODS: We applied either AS, the butanol-extracted fraction of AS (Bu-OH) or 3,5-dicaffeoyl-epi-quinic acid (DEQA, a major component of Bu-OH) topically for 3 weeks to 2,4-dinitrofluorobenzene (DNFB)-induced skin lesions in BALB/c mice. RESULTS: AS, Bu-OH and DEQA suppressed the clinical symptoms of DNFB-induced skin lesions and he associated scratching behaviour. Numbers of inflammatory cells infiltrating skin lesions were significantly reduced by AS or Bu-OH application but not by DEQA. In addition, AS significantly suppressed serum levels of histamine and IgE, while Bu-OH significantly suppressed serum levels of histamine, IgE, thymic stromal lymphopoietin (TSLP), interleukin (IL)-4 and IL-6, and DEQA significantly suppressed serum levels of histamine, IgE, TSLP and IL-4 in DNFB-induced AD mice. In skin lesions, AS and Bu-OH significantly reduced inflammatory cytokines, whereas DEQA did not. AS, Bu-OH and DEQA all significantly suppressed caspase-1 activities. CONCLUSIONS: These results demonstrate the anti-AD effects of AS, Bu-OH and DEQA, and suggest that all three have therapeutic potential.

Src-type tyrosine kinase p56lck is critical for thymic stromal lymphopoietin-induced allergic rhinitis.

BACKGROUND: Thymic stromal lymphopoietin (TSLP) is a regulator of mast cell-mediated allergic inflammatory reactions, but the manner in which TSLP contributes to allergic rhinitis (AR) remains unclear. OBJECTIVE: Here, we sought to determine that TSLP plays a crucial role in AR by interacting with Src-type tyrosine kinase p56lck and STAT6 and promoting mast cells degranulation. METHODS: The effects of TSLP on mast cell degranulation and AR were analysed in human mast cell line (HMC-1 cells), ovalbumin (OVA)-induced AR animal model, and human subjects. Small interfering RNA experiments were performed in HMC-1 cells and OVA-induced AR model. Immune responses were analysed by enzyme-linked immunosorbent assay, Western blotting, immunoprecipitation, and histological studies. RESULTS: Thymic stromal lymphopoietin levels and mast cell-derived p56lck activation were elevated in human subjects with AR, and in AR mice, exogenous TSLP accelerated TH2-allergic inflammatory reactions by up-regulating p56lck and STAT6. On the other hand, depletion of TSLP, p56lck, and STAT6 ameliorated clinical symptoms in AR mice. The selective inhibitor of p56lck, damnacanthal, inhibits AR reactions. CONCLUSION: Collectively, these observations suggest a role for TSLP/p56lck/STAT6 in AR and offer insight into potential therapeutic strategies.

Reliability and validity of the Atopic Dermatitis Symptom Score (ADSS).

BACKGROUND: We have developed the Atopic Dermatitis Symptom Score (ADSS) by which patients or parents can easily assess and record AD symptoms on a daily basis in a smartphone application. The aim of this study was to evaluate the reliability and validity of the ADSS. METHODS: We enrolled 307 children and adolescents with AD. Parents or caregivers were asked to record daily symptoms of the patients (itching, sleep disturbance, erythema, dryness, oozing, and edema) using a scale of 0-4. Statistical analyses consisted of the test-retest reliability, concurrent validity, minimal clinically important difference (MCID), responsiveness, floor or ceiling effects, and screening accuracy. Receiver-operating characteristic analyses were conducted to evaluate the ADSS cutoff point for predicting severe AD (SCORing AD [SCORAD] ≥40). RESULTS: Test-retest reliability between daytime and night-time ADSS was good (intraclass correlation coefficient, 0.82 [95% CI: 0.70-0.90]). An increase in ADSS was significantly associated with an increase in SCORAD (r = 0.64, P < .0001) (concurrent validity). The MCID was 4.1 points for the ADSS. There was a significant association between changes in ADSS and SCORAD (r = 0.56, P < .0001), indicating good responsiveness. At the optimal ADSS cutoff value of 7.0, sensitivity, specificity, and positive and negative predictive values were 88.4%, 78.6%, 21.1%, and 99.1%, respectively (screening accuracy). CONCLUSIONS: The ADSS can be a useful tool for self-assessment of skin symptoms in children with AD.

iNKT cells prevent obesity-induced hepatic steatosis in mice in a C-C chemokine receptor 7-dependent manner.

Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are characterized by an increase in hepatic triglyceride content with infiltration of immune cells, which can cause steatohepatitis and hepatic insulin resistance. C-C chemokine receptor 7 (CCR7) is primarily expressed in immune cells, and CCR7 deficiency leads to the development of multi-organ autoimmunity, chronic renal disease and autoimmune diabetes. Here, we investigated the effect of CCR7 on hepatic steatosis in a mouse model and its underlying mechanism. Our results demonstrated that body and liver weights were higher in the CCR7-/- mice than in the wild-type (WT) mice when they were fed a high-fat diet. Further, glucose tolerance and insulin sensitivity were markedly diminished in CCR7-/- mice. The number of invariant natural killer T (iNKT) cells was reduced in the livers of the CCR7-/- mice. Moreover, liver inflammation was detected in obese CCR7-/- mice, which was ameliorated by the adoptive transfer of hepatic mononuclear cells from WT mice, but not through the transfer of hepatic mononuclear cells from CD1d-/- or interleukin-10-deficient (IL-10-/-) mice. Overall, these results suggest that CCR7+ mononuclear cells in the liver could regulate obesity-induced hepatic steatosis via induction of IL-10-expressing iNKT cells.

The ACRA Anatomy Study (Assessment of Disability After Coronary Procedures Using Radial Access): A Comprehensive Anatomic and Functional Assessment of the Vasculature of the Hand and Relation to Outcome After Transradial Catheterization.

BACKGROUND: The palmar arches serve as the most important conduits for digital blood supply, and incompleteness may lead to digital ischemia when the radial artery becomes obstructed after cardiac catheterization. The rate of palmar arch incompleteness and the clinical consequences after transradial access are currently unknown. METHODS AND RESULTS: The vascular anatomy of the hand was documented by angiography in 234 patients undergoing transradial cardiac catheterization. In all patients, a preprocedural modified Allen test and Barbeau test were performed. Upper-extremity function was assessed at baseline and 2-year follow-up by the QuickDASH. Incompleteness of the superficial palmar arch (SPA) was present in 46%, the deep palmar arch was complete in all patients. Modified Allen test and Barbeau test results were associated with incompleteness of the SPA (P=0.001 and P=0.001). The modified Allen test had a 33% sensitivity and 86% specificity for SPA incompleteness with a cutoff value of >10 seconds and a 59% sensitivity and 60% specificity with a cutoff value of >5 seconds. The Barbeau test had a 7% sensitivity and 98% specificity for type D and a 21% sensitivity and 93% specificity for types C and D combined. Upper-extremity dysfunction was not associated with SPA incompleteness (P=0.77). CONCLUSIONS: Although incompleteness of the SPA is common, digital blood supply is always preserved by a complete deep palmar arch. Preprocedural patency tests have thus no added benefit to prevent ischemic complications of the hand. Finally, incompleteness of the SPA is not associated with a loss of upper-extremity function after transradial catheterization.

Satisfaction, function and repair integrity after arthroscopic versus mini-open rotator cuff repair.

AIMS: Advances in arthroscopic techniques for rotator cuff repair have made the mini-open approach less popular. However, the mini-open approach remains an important technique for repair for many surgeons. The aims of this study were to compare the integrity of the repair, the function of the shoulder and satisfaction post-operatively using these two techniques in patients aged > 50 years. PATIENTS AND METHODS: We identified 22 patients treated with mini-open and 128 patients treated with arthroscopic rotator cuff repair of July 2007 and June 2011. The mean follow-up was two years (1 to 5). Outcome was assessed using the American Shoulder and Elbow Surgeons (ASES) and Simple Shoulder Test (SST) scores, and satisfaction. The integrity of the repair was assessed using ultrasonography. A power analysis ensured sufficient enrolment. RESULTS: There was no statistically significant difference between the age, function, satisfaction, or pain scores (p > 0.05) of the two groups. The integrity of the repair and the mean SST scores were significantly better in the mini-open group (91% of mini-open repairs were intact versus 60% of arthroscopic repairs, p = 0.023; mean SST score 10.9 (standard deviation (sd) 1.3) in the mini-open group; 8.9 (sd 3.5) in arthroscopic group; p = 0.003). The ASES scores were also higher in the mini-open group (mean ASES score 91.0 (sd 10.5) in mini-open group; mean 82.70 (sd 19.8) in the arthroscopic group; p = 0.048). CONCLUSION: The integrity of the repair and function of the shoulder were better after a mini-open repair than after arthroscopic repair of a rotator cuff tear in these patients. The functional difference did not translate into a difference in satisfaction. Mini-open rotator cuff repair remains a useful technique despite advances in arthroscopy. Cite this article: Bone Joint J 2017;99-B:245-9.

Gut commensal Bacteroides acidifaciens prevents obesity and improves insulin sensitivity in mice.

In humans, the composition of gut commensal bacteria is closely correlated with obesity. The bacteria modulate metabolites and influence host immunity. In this study, we attempted to determine whether there is a direct correlation between specific commensal bacteria and host metabolism. As mice aged, we found significantly reduced body weight and fat mass in Atg7ΔCD11c mice when compared with Atg7f/f mice. When mice shared commensal bacteria by co-housing or feces transfer experiments, body weight and fat mass were similar in both mouse groups. By pyrosequencing analysis, Bacteroides acidifaciens (BA) was significantly increased in feces of Atg7ΔCD11c mice compared with those of control Atg7f/f mice. Wild-type C57BL/6 (B6) mice fed with BA were significantly more likely to gain less weight and fat mass than mice fed with PBS. Of note, the expression level of peroxisome proliferator-activated receptor alpha (PPARα) was consistently increased in the adipose tissues of Atg7ΔCD11c mice, B6 mice transferred with fecal microbiota of Atg7ΔCD11c mice, and BA-fed B6 mice. Furthermore, B6 mice fed with BA showed elevated insulin levels in serum, accompanied by increased serum glucagon-like peptide-1 and decreased intestinal dipeptidyl peptidase-4. These finding suggest that BA may have potential for treatment of metabolic diseases such as diabetes and obesity.

The circulating sphingosine-1-phosphate level predicts incident fracture in postmenopausal women: a 3.5-year follow-up observation study.

UNLABELLED: A high level of circulating sphingosine-1-phosphate (S1P) is associated with a high incidence of osteoporotic fracture and a high rate of an insufficient response to bisphosphonate therapy. INTRODUCTION: Sphingosine-1-phosphate (S1P) is a significant regulator of bone metabolism. Recently, we found that a high plasma S1P level is associated with low bone mineral density (BMD), high levels of bone resorption markers (BRMs), and a high risk of prevalent vertebral fracture in postmenopausal women. We investigated the possibility that S1P is a predictor of incident fracture. METHODS: A total of 248 postmenopausal women participated in this longitudinal study and were followed up for a mean duration of 3.5 years (untreated [n = 76] or treated with bisphosphonate or hormone replacement therapy [n = 172]). The baseline plasma S1P level and prevalent and incident fracture occurrence were assessed. RESULTS: A high S1P level was significantly associated with a higher rate of prevalent fracture after adjusting for femoral neck (FN) BMD, BRM, and potential confounders (odds ratio = 2.05; 95 % confidence interval [CI] = 1.03-4.00). Incident fractures occurred more frequently in the highest S1P tertile (T3) than in the lower two tertiles (T1-2) after adjusting for confounders, including baseline FN BMD, prevalent fracture, antiosteoporotic medication, annualized changes in FN BMD, BRM, and potential confounders (hazard ratio = 5.52; 95 % CI = 1.04-56.54). Insufficient response to bisphosphonate therapy occurred more frequently in T3 than T1-2 (odds ratio = 4.43; 95 % CI = 1.02-21.25). CONCLUSIONS: The plasma S1P level may be a potential predictor of fracture occurrence and an insufficient response to bisphosphonate therapy in postmenopausal women.

Profiling of rectal cancers MRI in pathological complete remission states after neoadjuvant concurrent chemoradiation therapy.

AIM: To fully characterise the magnetic resonance imaging (MRI) traits of rectal cancers in a large sample of patients, each experiencing pathological complete remission (pCR) after neoadjuvant concurrent chemoradiation therapy (CCRT). MATERIALS AND METHODS: A total of 120 patients (77 male, 43 female; median age, 59.5 years; range, 32-81 years) with rectal cancers in CCRT-induced pCR states who underwent pre- and post-CCRT MRI and eventual surgery between July, 2005 and September, 2014 were retrospectively reviewed. In most (n=100), diffusion-weighted imaging was also performed. Tumour volume, tumour regression grade (TRG), T-stage, mesorectal fascia (MRF) status, and T2 signal intensity (T2-SI) were analysed. Paired t-test and McNemar's test were applied for statistical comparisons. RESULTS: Tumour volume declined sharply after CCRT (pre-CCRT, 21.5 ± 22.4 cm(3); post-CCRT, 6.6 ± 8.4 cm(3); p<0.001). TRG distribution was as follows: G1 (clinical CR), 3; G2, 38; G3, 78; G4, 1; and G5 (marked progression), 0. Downstaging of T-stage (34%,16/47) and MRF status (19.7%,13/66) did occur; but on post-CCRT MRI, 25.8% (31/120) remained at T3 ≥ 5 mm or T4 stage, and 44.2% (53/120) were MRF-positive. A majority (88.3%, 106/120) of patients displayed intermediate T2-SI prior to CCRT. Most converted to dark T2-SI after CCRT, with 12.5% (15/120) unchanged. On post-CCRT MRI, 11% (11/100) of patients showed diffusion restriction. CONCLUSION: MRI findings in CCRT-induced pCR-status rectal cancers were highly variable. Tumour volume and T2-SI mostly decreased; however, such lesions occasionally presented with unexpected atypical features, such as large residual volume and/or intermediate T2-SI.

Correlates of family involvement before and during medical visits among older adults with high-risk diabetes.

AIMS: To examine the characteristics of patients with diabetes who regularly receive help from a supporter in preparing for and attending medical visits, and the association between this help and clinical risk factors for diabetes complications. METHODS: We linked survey data about family involvement for patients in the Veterans Health Administration system with poorly controlled Type 2 diabetes (n = 588; mean 67 years; 97% male) with health record data on blood pressure, glycaemic control and prescription-fill gaps. We used multivariable regression to assess whether supporter presence and, among patients with supporters, supporter role (visit preparation, accompaniment to medical visit or no involvement) were associated with concurrent trends in clinical risk factors over 2 years, adjusting for sociodemographic and health characteristics. RESULTS: Most patients (78%) had a main health supporter; of these, more had regular support for preparing for appointments (69%) than were regularly accompanied to them (45%). Patients with preparation help only were younger and more educated than accompanied patients. Support presence and type was not significantly associated with clinical risk factors. CONCLUSIONS: Family help preparing for appointments was common among these patients with high-risk diabetes. In its current form, family support for medical visits may not affect clinical factors in the short term. Supporters helping patients engage in medical visits may need training and assistance to have an impact on the clinical trajectory of patients with diabetes.

Inhibition of breast cancer invasion by TIS21/BTG2/Pc3-Akt1-Sp1-Nox4 pathway targeting actin nucleators, mDia genes.

The mammalian homolog of Drosophila diaphanous (mDia), actin nucleator, has been known to participate in the process of invasion and metastasis of cancer cells via regulating a number of actin-related biological processes. We have previously reported that tumor suppressor TIS21(/BTG2/Pc3) (TIS21) inhibits invadopodia formation by downregulating reactive oxygen species (ROS) in MDA-MB-231 cells. We herein report that TIS21(/BTG2/Pc3) downregulates diaphanous-related formin (DRF) expression via reducing NADPH oxidase 4 (Nox4)-derived ROS generation by Akt1 activation and subsequently impairs invasion activity of the highly invasive breast cancer cells. Knockdown of Akt1 by RNA interference recovered the TIS21(/BTG2/Pc3)-inhibited F-actin remodeling and ROS generation by recovering Nox4 expression. Furthermore, Sp1-mediated Nox4 transcription was downregulated by TIS21(/BTG2/Pc3)-Akt1 signals, leading to the inhibition of cancer cell invasion via F-actin remodeling by mDia genes. To our best knowledge, this is the first study to show that TIS21(/BTG2/Pc3)-Akt1 inhibited Sp1-Nox4-ROS cascade, subsequently reducing invasion activity via inhibition of mDia family genes.