Prediction of preterm birth with and without preeclampsia using mid-pregnancy immune and growth-related molecular factors and maternal characteristics.

OBJECTIVE:To evaluate if mid-pregnancy immune and growth-related molecular factors predict preterm birth (PTB) with and without (±) preeclampsia. STUDY DESIGN:Included were 400 women with singleton deliveries in California in 2009-2010 (200 PTB and 200 term) divided into training and testing samples at a 2:1 ratio. Sixty-three markers were tested in 15-20 serum samples using multiplex technology. Linear discriminate analysis was used to create a discriminate function. Model performance was assessed using area under the receiver operating characteristic curve (AUC). RESULTS:Twenty-five serum biomarkers along with maternal age <34 years and poverty status identified >80% of women with PTB ± preeclampsia with best performance in women with preterm preeclampsia (AUC = 0.889, 95% confidence interval (0.822-0.959) training; 0.883 (0.804-0.963) testing). CONCLUSION:Together with maternal age and poverty status, mid-pregnancy immune and growth factors reliably identified most women who went on to have a PTB ± preeclampsia

Hemi-Castaing ligamentoplasty for the treatment of chronic lateral ankle instability: a retrospective assessment of outcome

Purpose: In the treatment of chronic ankle instability, most non-anatomical reconstructions use the peroneus brevis tendon. This, however, sacrifices the natural ankle stabilising properties of the peroneus brevis muscle. The aim of this study was to evaluate the functional outcome of patients treated with a hemi-Castaing procedure, which uses only half the peroneus brevis tendon. Methods: We performed a retrospective cohort study of patients who underwent hemi-Castaing ligamentoplasty for chronic lateral ankle instability between 1993 and 2010, with a minimum of one year follow-up. Patients were sent a postal questionnaire comprising five validated outcome measures: Olerud-Molander Ankle Score (OMAS), Karlsson Ankle Functional Score (KAFS), Tegner Activity Level Score (pre-injury, prior to surgery, at follow-up), visual analog scale on pain (VAS) and the Short Form 36 (SF-36). Results: Twenty patients completed the questionnaire on functional outcome. The OMAS showed good to excellent outcome in 80% and the KAFS in 65%, the Tegner Score improved from surgery but did not reach pre-injury levels, the VAS on pain was 1 of 10 and the SF-36 returned to normal compared with the average population. Conclusions: Even though most patients were satisfied with the results, outcome at long-term follow-up was less favourable compared with the literature on anatomical reconstructions. In accordance with the literature, we therefore conclude that the initial surgical treatment of chronic lateral ankle instability should be an anatomical repair with augmentation (i.e. the Broström-Gould technique) and the non-anatomical repair should be reserved for unsuccessful cases after anatomical repair or in cases where no adequate ligament remnants are available for reconstruction

Breast cancer biomarkers predict weight loss after gastric bypass surgery

<p>Abstract</p> <p>Background</p> <p>Obesity has long been associated with postmenopausal breast cancer risk and more recently with premenopausal breast cancer risk. We previously observed that nipple aspirate fluid (n) levels of prostate specific antigen (PSA) were associated with obesity. Serum (s) levels of adiponectin are lower in women with higher body mass index (BMI) and with breast cancer. We conducted a prospective study of obese women who underwent gastric bypass surgery to determine: 1) change in n- and s-adiponectin and nPSA after surgery and 2) if biomarker change is related to change in BMI. Samples (30-s, 28-n) and BMI were obtained from women 0, 3, 6 and 12 months after surgery.</p> <p>Findings</p> <p>There was a significant increase after surgery in pre- but not postmenopausal women at all time points in s-adiponectin and at 3 and 6 months in n-adiponectin. Low n-PSA and high s-adiponectin values were highly correlated with decrease in BMI from baseline.</p> <p>Conclusions</p> <p>Adiponectin increases locally in the breast and systemically in premenopausal women after gastric bypass. s-adiponectin in pre- and nPSA in postmenopausal women correlated with greater weight loss. This study provides preliminary evidence for biologic markers to predict weight loss after gastric bypass surgery.</p

Plantar calcaneal spurs in older people: longitudinal traction or vertical compression?

<p>Abstract</p> <p>Background</p> <p>Plantar calcaneal spurs are common, however their pathophysiology is poorly understood. This study aimed to evaluate the prevalence and correlates of plantar calcaneal spurs in a large sample of older people.</p> <p>Methods</p> <p>Weightbearing lateral foot radiographs of 216 people (140 women and 76 men) aged 62 to 94 years (mean age 75.9, <smcaps>SD</smcaps> 6.6) were examined for plantar calcaneal and Achilles tendon spurs. Associations between the presence of spurs and sex, body mass index, radiographic measures of foot posture, self-reported co-morbidities and current or previous heel pain were then explored.</p> <p>Results</p> <p>Of the 216 participants, 119 (55%) had at least one plantar calcaneal spur and 103 (48%) had at least one Achilles tendon spur. Those with plantar calcaneal spurs were more likely to have Achilles tendon spurs (odds ratio [OR] = 2.0, 95% confidence interval [CI] 1.2 to 3.5). Prevalence of spurs did not differ according to sex. Participants with plantar calcaneal spurs were more likely to be obese (OR = 7.9, 95% CI 3.6 to 17.0), report osteoarthritis (OR = 2.6, 95% CI 1.6 to 4.8) and have current or previous heel pain (OR = 4.6, 95% CI 2.3 to 9.4). No relationship was found between the presence of calcaneal spurs and radiographic measures of foot posture.</p> <p>Conclusion</p> <p>Calcaneal spurs are common in older men and women and are related to obesity, osteoarthritis and current or previous heel pain, but are unrelated to radiographic measurements of foot posture. These findings support the theory that plantar calcaneal spurs may be an adaptive response to vertical compression of the heel rather than longitudinal traction at the calcaneal enthesis.</p

Adiponectin Haploinsufficiency Promotes Mammary Tumor Development in MMTV-PyVT Mice by Modulation of Phosphatase and Tensin Homolog Activities

Background: Adiponectin is an adipokine possessing beneficial effects on obesity-related medical complications. A negative association of adiponectin levels with breast cancer development has been demonstrated. However, the precise role of adiponectin deficiency in mammary carcinogenesis remains elusive. Methodology/Principal Findings: In the present study, MMTV-polyomavirus middle T antigen (MMTV-PyVT) transgenic mice with reduced adiponectin expressions were established and the stromal effects of adiponectin haploinsufficiency on mammary tumor development evaluated. In mice from both FVB/N and C57BL/6J backgrounds, insufficient adiponectin production promoted mammary tumor onset and development. A distinctive basal-like subtype of tumors, with a more aggressive phenotype, was derived from adiponectin haplodeficient MMTV-PyVT mice. Comparing with those from control MMTV-PyVT mice, the isolated mammary tumor cells showed enhanced tumor progression in re-implanted nude mice, accelerated proliferation in primary cultures, and hyperactivated phosphatidylinositol-3-kinase (PI3K)/Akt/beta-catenin signaling, which at least partly attributed to the decreased phosphatase and tensin homolog (PTEN) activities. Further analysis revealed that PTEN was inactivated by a redox-regulated mechanism. Increased association of PTEN-thioredoxin complexes was detected in tumors derived from mice with reduced adiponectin levels. The activities of thioredoxin (Trx1) and thioredoxin reductase (TrxR1) were significantly elevated, whereas treatment with either curcumin, an irreversible inhibitor of TrxR1, or adiponectin largely attenuated their activities and resulted in the re-activation of PTEN in these tumor cells. Moreover, adiponectin could inhibit TrxR1 promoter-mediated transcription and restore the mRNA expressions of TrxR1. Conclusion: Adiponectin haploinsufficiency facilitated mammary tumorigenesis by down-regulation of PTEN activity and activation of PI3K/ Akt signalling pathway through a mechanism involving Trx1/TrxR1 redox regulations. © 2009 Lam et al.published_or_final_versio

New monoclonal antibodies to defined cell surface proteins on human pluripotent stem cells

The study and application of human pluripotent stem cells (hPSCs) will be enhanced by the availability of well-characterized monoclonal antibodies (mAbs) detecting cell-surface epitopes. Here, we report generation of seven new mAbs that detect cell surface proteins present on live and fixed human ES cells (hESCs) and human iPS cells (hiPSCs), confirming our previous prediction that these proteins were present on the cell surface of hPSCs. The mAbs all show a high correlation with POU5F1 (OCT4) expression and other hPSC surface markers (TRA-160 and SSEA-4) in hPSC cultures and detect rare OCT4 positive cells in differentiated cell cultures. These mAbs are immunoreactive to cell surface protein epitopes on both primed and naive state hPSCs, providing useful research tools to investigate the cellular mechanisms underlying human pluripotency and states of cellular reprogramming. In addition, we report that subsets of the seven new mAbs are also immunoreactive to human bone marrow-derived mesenchymal stem cells (MSCs), normal human breast subsets and both normal and tumorigenic colorectal cell populations. The mAbs reported here should accelerate the investigation of the nature of pluripotency, and enable development of robust cell separation and tracing technologies to enrich or deplete for hPSCs and other human stem and somatic cell types. Stem Cells 2017;35:626-640.Carmel M. O'Brien, Hun S. Chy, Qi Zhou, Shiri Blumenfeld, Jack W. Lambshead, Xiaodong Liu ... et al

Leptin and Adiponectin: new players in the field of tumor cell and leukocyte migration

Adipose tissue is no longer considered to be solely an energy storage, but exerts important endocrine functions, which are primarily mediated by a network of various soluble factors derived from fat cells, called adipocytokines. In addition to their responsibility to influence energy homeostasis, new studies have identified important pathways linking metabolism with the immune system, and demonstrating a modulatory role of adipocytokines in immune function. Additionally, epidemiological studies underline that obesity represents a significant risk factor for the development of cancer, although the exact mechanism of this relationship remains to be determined. Whereas a possible influence of adipocytokines on the proliferation of tumor cells is already known, new evidence has come to light elucidating a modulatory role of this signaling substances in the regulation of migration of leukocytes and tumor cells. The migration of leukocytes is a key feature to fight cancer cells, whereas the locomotion of tumor cells is a prerequisite for tumor formation and metastasis. We herein review the latest tumor biological findings on the role of the most prominent adipocytokines leptin and adiponectin, which are secreted by fat cells, and which are involved in leukocyte migration, tumor growth, invasion and metastasis. This review thus accentuates the complex, interactive involvement of adipocytokines in the regulation of migration of both leukocytes and tumor cells, and gives an insight in the underlying molecular mechanisms

Is there a difference between child self-ratings and parent proxy-ratings of the quality of life of children with a diagnosis of Attention Deficit Hyperactivity Disorder (ADHD)? A systematic review of the literature

There are contemporary indicators that parent proxy-ratings and child self-ratings of a child’s quality of life (QoL) are not interchangeable. This review examines dual informant studies to assess parent–child agreement on the QoL of children with attention-deficit/hyperactivity disorder. A systematic search of four major databases (PsycINFO, MEDLINE, EMBASE and Cochrane databases) was completed, and related peer-reviewed journals were hand-searched. Studies which reported quantitative QoL ratings for matched parent and child dyads were screened in accordance with relevant inclusion and exclusion criteria. Key findings were extracted from thirteen relevant studies, which were rated for conformity to the recommendations of an adapted version of the STROBE statement guidelines for observational studies. In the majority of studies reviewed, children rated their QoL more highly than their parents. There was some evidence for greater agreement on the physical health domain than psychosocial domains

Bright light therapy in pregnant women with major depressive disorder: Study protocol for a randomized, double-blind, controlled clinical trial

Background: Depression during pregnancy is a common and high impact disease. Generally, 5-10 % of pregnant women suffer from depression. Children who have been exposed to maternal depression during pregnancy have a higher risk of adverse birth outcomes and more often show cognitive, emotional and behavioural problems. Therefore, early detection and treatment of antepartum depression is necessary. Both psychotherapy and antidepressant medication, first choice treatments in a non-pregnant population, have limitations in treating depression during pregnancy. Therefore, it is urgent and relevant to investigate alternative treatments for antepartum depression. Bright light therapy (BLT) is a promising treatment for pregnant women with depressive disorder, for it combines direct availability, sufficient efficacy, low costs and high safety, taking the safety for the unborn child into account as well. Methods: In this study, 150 pregnant women (12-18 weeks pregnant) with a DSM-V diagnosis of depressive disorder will be randomly allocated in a 1:1 ratio to one of the two treatment arms: treatment with BLT (9.000 lux) or treatment with dim red light therapy (100 lux). Both groups will be treated for 6 weeks at home on a daily basis for 30 min, within 30 min of habitual wake-up time. Follow-up will take place after 6 weeks of therapy, 3 and 10 weeks after end of therapy, at birth and 2, 6 and 18 months postpartum. Primary outcome will be the average change in depressive symptoms between the two groups, as measured by the Structured Interview Guide for the Hamilton Depression Scale - Seasonal Affective Disorder version and the Edinburg Postnatal Depression Scale. Changes in rating scale scores of these questionnaires over time will be analysed using generalized linear mixed models. Secondary outcomes will be the changes in maternal cortisol and melatonin levels, in maternal sleep quality and gestational age, birth weight, infant behaviour, infant cortisol exposure and infant cortisol stress response. Discussion: If BLT reduces depressive symptoms in pregnant women, it will provide a safe, cheap, non-pharmacological and efficacious alternative treatment for psychotherapy and antidepressant medication in treating antepartum depression, without any expected adverse reactions for the unborn child. Trial registration: Netherlands Trial Register NTR5476. Registered 5 November 2015

Effect of a low fat versus a low carbohydrate weight loss dietary intervention on biomarkers of long term survival in breast cancer patients ('CHOICE'): study protocol

<p>Abstract</p> <p>Background</p> <p>Weight loss in overweight or obese breast cancer patients is associated with an improved prognosis for long term survival. However, it is not clear whether the macronutrient composition of the chosen weight loss dietary plan imparts further prognostic benefit. A study protocol is presented for a dietary intervention to investigate the effects of weight loss dietary patterns that vary markedly in fat and carbohydrate contents on biomarkers of exposure to metabolic processes that may promote tumorigenesis and that are predictive of long term survival. The study will also determine how much weight must be lost for biomarkers to change in a favorable direction.</p> <p>Methods/Design</p> <p>Approximately 370 overweight or obese postmenopausal breast cancer survivors (body mass index: 25.0 to 34.9 kg/m²) will be accrued and assigned to one of two weight loss intervention programs or a non-intervention control group. The dietary intervention is implemented in a free living population to test the two extremes of popular weight loss dietary patterns: a high carbohydrate, low fat diet versus a low carbohydrate, high fat diet. The effects of these dietary patterns on biomarkers for glucose homeostasis, chronic inflammation, cellular oxidation, and steroid sex hormone metabolism will be measured. Participants will attend 3 screening and dietary education visits, and 7 monthly one-on-one dietary counseling and clinical data measurement visits in addition to 5 group visits in the intervention arms. Participants in the control arm will attend two clinical data measurement visits at baseline and 6 months. The primary outcome is high sensitivity C-reactive protein. Secondary outcomes include interleukin-6, tumor necrosis factor-α, insulin-like growth factor-1 (IGF), IGF binding protein-3, 8-isoprostane-F2-alpha, estrone, estradiol, progesterone, sex hormone binding globulin, adiponectin, and leptin.</p> <p>Discussion</p> <p>While clinical data indicate that excess weight for height is associated with poor prognosis for long term survival, little attention is paid to weight control in the clinical management of breast cancer. This study will provide information that can be used to answer important patient questions about the effects of dietary pattern and magnitude of weight loss on long term survival following breast cancer treatment.</p> <p>Clinical Trial Registration</p> <p>CA125243</p