The equity impact of brief opportunistic interventions to promote weight loss in primary care: secondary analysis of the BWeL randomised trial.

BACKGROUND: Guidelines recommend that clinicians should make brief opportunistic behavioural interventions to patients who are obese to increase the uptake of effective weight loss programmes. The objective was to assess the effect of this policy on socioeconomic equity. METHODS: One thousand eight hundred eighty-two consecutively attending patients with obesity and who were not seeking support for weight loss from their GP were enrolled in a trial. Towards the end of each consultation, GPs randomly assigned participants to one of two 30-s interventions. In the active intervention (support arm), the GP offered referral to a weight management group. In the control intervention (advice arm), the GP advised the patient that their health would benefit from weight loss. Agreement to attend a behavioural weight loss programme, attendance at the programme and weight loss at 12 months were analysed by socioeconomic status, measured by postcode using the Index of Multiple Deprivation (IMD). RESULTS: Mean weight loss was 2.43 kg (sd 6.49) in the support group and 1.04 kg (sd 5.50) for the advice only group, but these effects were moderated by IMD (p = 0.039 for the interaction). In the support arm, weight loss was greater in higher socioeconomic groups. Participants from lower socioeconomic backgrounds were more likely to accept the offer and equally likely to attend a weight loss referral but attended fewer sessions. Adjusting for these sequentially reduced the gradient for the association of socioeconomic status with weight loss from + 0.035 to - 0.001 kg/IMD point. In the advice only arm, 10% took effective action to promote weight loss. The decision to seek support for weight loss outside of the trial did not differ by socioeconomic status, but weight loss among deprived participants who used external support was greater than among more affluent participants (p = 0.025). CONCLUSION: Participants' responses to GPs' brief opportunistic interventions to promote weight loss differed by socioeconomic status and trial arm. In the support arm, more deprived people lost less weight because they attended fewer sessions at the programme. In the advice arm, more deprived people who sought and paid for support for weight loss themselves lost more weight than more affluent people who sought support. TRIAL REGISTRATION: This trial is registered with the ISRCTN registry, number ISRCTN26563137 . Date of registration: January 3, 2013; date of first participant recruited: June 4, 2014.

Pregnancy-related severe pelvic girdle pain caused by unilateral noninfectious sacroiliitis. A case report and literature review.

Pelvic girdle pain during and after pregnancy is the clinical syndrome of persistent musculoskeletal pain localized in the posterior and/or anterior aspect of the pelvis originating from sacroiliac joints and/or pubic symphysis due to dynamic instability. We report the case of severe and disabling postpartum pelvic girdle pain caused by unilateral noninfectious sacroiliitis which resolved after 2 months by nonsteroidal anti-inflammatory drug and physical therapy. A short literature review is given on epidemiology, etiology, clinical presentation, therapy, and prognosis of pregnancy-related pelvic girdle pain.

A focus group interview of university students7 health in Sri Lanka / 国際保健医療

<B>Objective</B><BR>Despite the steady high prevalence of infectious diseases, Sri Lanka has an increasing awareness of lifestyle-related health diseases. To lower their risks in the future, making better lifestyle choices and establishing patterns of healthy behavior during young adulthood are essential. The purpose of this qualitative study was to explore current issues of university students' health behaviors and their environments.<BR><B>Methods</B><BR>The study was conducted in a university of the Central Province, Sri Lanka. Four graduate students in the Faculty of Medicine and three senior students in the Faculty of the Arts were interviewed in a focus group. Interviews were tape-recorded, transcribed, and analyzed inductively.<BR><B>Results</B><BR>The results yielded three core categories: little interests in health, unhealthy lifestyles, and lower usage of the Student Health Center. In addition, three major health problems were observed among the participants: eating habits, substance use, and mental health. Students had little paid attention to their health. It also showed passive participation on a health check-up. Additionally students' hidden risky behaviors were observed: alcohol intake and smoking. Mental health problem is one of the great health concerns among the students. Although the School Health Center was available, the gaps between its provisions of services and students' needs are an important issue.<BR><B>Discussion and Conclusion</B><BR>Students need to pay more attention on their health conditions and the importance of preventive health. Furthermore, to improve the current university health services, accessibility, usability, and students' needs should be carefully reviewed in the context of advocacy of preventive health behaviors.

Phase I feasibility trial of stereotactic body radiation therapy for primary hepatocellular carcinoma

BACKGROUND: Hepatocellular carcinoma (HCC) is increasing in incidence and the majority of patients are not candidates for radical therapies. Therefore, interest in minimally invasive therapies in growing. METHODS: A Phase I dose escalation trial was conducted at Indiana University to determine the feasibility and toxicity of stereotactic body radiation therapy (SBRT) for primary HCC. Eligible patients had Child-Turcotte-Pugh's Class (CTP) A or B, were not candidates for resection, had 1-3 lesions and cumulative tumour diameter less than or equal to 6 cm. Dose escalation started at 36 Gy in 3 fractions (12 Gy/fraction) with a subsequent planned escalation of 2 Gy/ fraction/level. Dose-limiting toxicity (DLT) was defined as Common Terminology Criteria for Adverse Events v3.0 grade 3 or greater toxicity. RESULTS: Seventeen patients with 25 lesions were enrolled. Dose was escalated to 48 Gy (16 Gy/fraction) in CTP-A patients without DLT. Two patients with CPC-B disease developed grade 3 hepatic toxicity at the 42-Gy (14 Gy/fraction) level. The protocol was amended for subsequent CTP-B patients to receive a regimen of 5 fractions starting at 40 Gy (8 Gy/fraction) with one patient experiencing progressive liver failure. Four additional patients were enrolled (one died of unrelated causes after an incomplete SBRT course) without DLT. The only factor related to more than one grade 3 or greater liver toxicity or death within 6 months was the CTP score (p=0.03). Six patients underwent a liver transplant. Ten patients are alive without progression with a median FU of 24 months (10-42 months), with local control/stabilisation of the disease of 100%. One and two-year Kaplan-Meier estimates for overall survival are 75% and 60%, respectively. CONCLUSIONS: SBRT is a non-invasive feasible and well tolerated therapy in adequately selected patients with HCC. The preliminary local control and survival are encouraging. A confirmatory Phase II trial is currently open to accrual (AU)

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Cytokines modulate endothelial cell intracellular signal transduction required for VCAM-1-dependent lymphocyte transendothelial migration.

Vascular cell adhesion molecule-1 (VCAM-1) activates endothelial cell NADPH oxidase which catalyzes production of reactive oxygen species (ROS). This activity is required for VCAM-1-dependent lymphocyte migration. The focus of our study was to determine whether these VCAM-1-dependent functions are modulated by cytokines. TGF-beta1 or IFN-gamma pretreatment of mouse endothelial cell lines inhibited VCAM-1-dependent B and T cell transendothelial migration without affecting initial lymphocyte adhesion. Neutralizing anti-TGF-beta1 blocked the effects of TGF-beta1 pretreatment of endothelial cells, whereas addition of anti-TGF-beta1 after TGF-beta1 pretreatment of the endothelial cells did not block TGF-beta1-mediated inhibition. Neutralizing anti-IFN-gamma also blocked the inhibitory effects of IFN-gamma. TGF-beta1 and IFN-gamma blocked migration by inhibiting the VCAM-1-stimulated production of low levels of ROS (0.1-0.9 microM H2O2). These results demonstrate that both TGF-beta1 and IFN-gamma directly affect the endothelial cells' ability to promote lymphocyte migration. IL-4 had differing effects on T and B cells during transmigration. IL-4 augmented T cell migration across the endothelial cell lines but did not affect T cell adhesion. Conversely, IL-4 increased B cell adhesion to the endothelial cell lines without affecting migration. In summary, cytokines can directly modulate microvascular endothelial cell intracellular signaling, demonstrating a new level of cytokine regulation of lymphocyte diapedesis.

Early B-lymphocyte precursors and their regulation by sex steroids.

This review describes an improved characterization of early B-lymphocyte precursors in mice and the remarkable sensitivity of the same cells to hormones. The nuclear enzyme terminal deoxynucleotidyl transferase (TdT) was used as a marker to image and characterize bone marrow cells lacking all lineage-associated markers. Most early TdT+ precursors have a distinctive density of c-kit and express the interleukin-7Ralpha chain, as well as flt-3/flk2, but lack CD34. An understanding of those cell surface properties made it possible to obtain highly enriched, viable cells with the potential to give rise to CD19+ lymphocytes in culture. A series of other flow cytometry and culture experiments suggested a possible differentiation sequence for these early pro-B cells. This new model was used to advantage in our studies of sex steroids. It appears that early precursors represent a hormone-sensitive control point for determining numbers of new B lymphocytes that are produced within bone marrow. We also compare and contrast these findings with B lymphopoiesis in humans.

Effect of subcutaneous vs intramuscular administration of P.G. 600 on estrual and ovulatory responses of prepubertal gilts.

The effects of s.c. and i.m. administration of P.G. 600 on estrual and ovulatory responses of prepubertal gilts were investigated. One hundred eighty-four crossbred gilts between 159 and 174 d of age were assigned to receive P.G. 600 s.c. (s.c. P.G. 600) in the flank, P.G. 600 i.m. in the neck (i.m. P.G. 600), or no treatment (control). At the beginning of the study (d 0), animals were selected from a modified, open-front barn, regrouped, relocated to new pens, and exposed once daily to a mature boar to check for estrus. On d 17, ovaries were collected from all gilts and analyzed for the presence of corpora lutea (CL), cystic follicles, and cystic CL. A higher proportion of gilts expressed estrus with s.c. P.G. 600 (76%) than with i.m. P.G. 600 (52%, P < .01) or controls (15%, P < .01). The interval from initiation of treatment on d 0 to estrus was reduced (P < .01) by P.G. 600 (4.6 d) compared to controls (5.9 d), but there was no significant difference between P.G. 600 treatments. Both s.c. P.G. 600 (86%) and i.m. P.G. 600 (77%) induced more gilts to ovulate (P < .01) than controls (18%), but there was no significant difference between P.G. 600 treatments. No significant effect of treatment was detected on number of CL (17.9), number of cystic follicles (1.5), or number of cystic CL (2.1). Proportions of gilts that developed cystic follicles or cystic CL were not influenced by treatment. Results of this study indicated that s.c. administration of P.G. 600 significantly improved the induction of estrus in prepubertal gilts compared to i.m. administration.

Novel alpha 4-integrin ligands on an endothelial cell line.

The unique combination of adhesion molecules expressed on endothelial cells is thought to mediate the specificity of leukocyte-endothelial cell interactions. In this study, murine endothelial cell lines were used as a model to identify novel adhesion molecules that participate in these cellular interactions. Lymphocyte adhesion to the continuous endothelial cell lines mHEVa and mHEVc required alpha 4-integrin. Interestingly, lymphocyte alpha 4-integrin bound to VCAM-1 as well as an unknown ligand on the mHEVa cell line. We have demonstrated that this VCAM-1-independent adhesion to the mHEVa cells was not mediated by other known alpha 4-integrin ligands (fibronectin, alpha 4-integrin itself, or MAdCAM-1). Two novel alpha 4-integrin ligands (p50 and p10) were isolated from the mHEVa cell line but not the mHEVc cell line by B cell alpha 4-integrin-specific ligand binding of radiolabeled mHEV cell membrane proteins. These results provide the first direct evidence that novel ligands for alpha 4-integrin exist on membranes from endothelial cells.

Functional assessment of precursors from murine bone marrow suggests a sequence of early B lineage differentiation events.

Most lineage marker-negative (Lin-)TdT+ cells from murine marrow lack CD34 but display c-kit at low density as well as IL-7Ralpha and Flk-2/Flt-3 receptors. Single cells with these characteristics generated CD45RA+CD19- as well as CD19+ lymphocytes in culture. CD45RA+CD19- marrow cells were resolved into three nonoverlapping subsets. One subset, lacking DX5 and Ly-6C antigens, yielded CD19+ cells in culture. Further analysis demonstrated CD24 on most Lin-TdT+ cells and all CD45R+CD19-DX5-Ly-6C- cells. Mac-1/CD11b was absent from these two subsets of B lineage precursors, while IL-7Ralpha was retained during subsequent differentiation to a CD19+ and stromal cell-independent stage. These findings contrast with previous descriptions of B lymphocyte precursors and suggest a sequence of early differentiation events.

Influence of norgestomet in combination with gonadotropins on induction of estrus and ovulation in prepubertal gilts.

Our objective was to determine whether priming with the progestogen norgestomet for 9 d would enhance estrual and ovulatory responses of prepubertal gilts to PG600 (400 IU eCG + 200 IU hCG). Gilts (140 to 190 d old) were assigned by litter, age, and weight to one of three treatments: 1) 9 d of norgestomet implant with an injection of PG600 after implant removal on d 9 (N+PG; n = 43); 2) no implant and an injection of PG600 on d 9 (PG; n = 36); or 3) neither implant nor PG600 (control; n = 29). Beginning on d 0, gilts were exposed once daily to a boar and checked until estrus was observed or until d 45 after the start of the experiment. Ovaries were examined for number of corpora lutea (CL) after estrus or at 45 d. Greater proportions of N+PG (63%, P < .05) and PG (69%, P < .01) gilts expressed estrus than did controls (34%), but proportions did not differ between N+PG and PG (P > .10). Among gilts in estrus following treatment with N+PG or PG, 100% showed estrus within 6 d after PG600 injection. For gilts that expressed estrus within 45 d, the average age at estrus was reduced (P < .05) by PG to 172 +/- 2 d compared with 182 +/- 4 d for controls. Average age at estrus did not differ (P > . 10) between PG and N+PG (177 +/- 2 d). Greater proportions of N+PG (82%; P < .001) and PG (65%; P < .001) gilts ovulated than controls (13%), but proportions did not differ between N+PG and PG (P > .10). The number of CL (20 +/- 2) was not affected by treatment and ranged from 2 to 71. There was no increase in ovarian cysts in response to treatment. Results indicated that norgestomet before PG600 did not enhance estrus expression or ovulation compared with PG600 alone, but use of PG600 increased the proportions of gilts that expressed estrus and ovulated compared with controls.

Human and murine high endothelial venule cells phagocytose apoptotic leukocytes.

Apoptotic cell death occurs during normal lymphocyte development and differentiation as well as following lymphocyte exposure to endogenous corticosteroids released during stress, malnutrition, and trauma. Recognition and engulfment of these apoptotic cells is important for the clearance of dying cells before they release potent inflammatory mediators into the vasculature or tissues. Phagocytosis of apoptotic cells is accomplished in part by macrophages. We report for the first time that apoptotic lymphocytes are also phagocytosed by high endothelial venule (HEV) cells. The murine HEV cell line mHEVa rapidly phagocytosed apoptotic lymphoid and myeloid cells with the greatest rate of phagocytosis occurring at 0-6 h. To confirm HEV cell interaction with apoptotic cells, we demonstrated that apoptotic human tonsil lymphocytes were phagocytosed by human tonsil HEV cells in primary cultures. Furthermore, we examined HEV cell phagocytosis in vivo. Mice were treated with a natural corticosterone (4-pregnene-11 beta,21-diol-3,20-dione) at levels detected during stress or malnutrition (93-180 micrograms serum cortisol/dl). At 4-12 h posttreatment, apoptotic lymphocytes were present inside vacuoles of HEV cells in axillary lymph node tissue sections, as determined by transmission electron microscopy. These data suggest that, in addition to macrophages, lymph node HEV cells also play a role in the removal of apoptotic lymphocytes. Moreover, since HEV cells are specialized endothelial cells that regulate lymphocyte migration into peripheral lymphoid tissues, they may provide an important checkpoint for clearance of apoptotic lymphocytes within the vasculature, as well as limiting entrance of nonfunctional lymphocytes into the lymph node.