Miracle-dz/UniFAR-FTUs huggingface dataset:
Diurnal rhythm of circulating nicotinamide phosphoribosyltransferase (Nampt/visfatin/PBEF): impact of sleep loss and relation to glucose metabolism.

CONTEXT Animal studies indicate that nicotinamide phosphoribosyltransferase [Nampt/visfatin/pre-B-cell colony-enhancing factor (PBEF)] contributes to the circadian fine-tuning of metabolic turnover. However, it is unknown whether circulating Nampt concentrations, which are elevated in type 2 diabetes and obesity, display a diurnal rhythm in humans. OBJECTIVE Our objective was to examine the 24-h profile of serum Nampt in humans under conditions of sleep and sleep deprivation and relate the Nampt pattern to morning postprandial glucose metabolism. INTERVENTION Fourteen healthy men participated in two 24-h sessions starting at 1800 h, including either regular 8-h-night sleep or continuous wakefulness. Serum Nampt and leptin were measured in 1.5- to 3-h intervals. In the morning, plasma glucose and serum insulin responses to standardized breakfast intake were determined. MAIN OUTCOME MEASURES Under regular sleep-wake conditions, Nampt levels displayed a pronounced diurnal rhythm, peaking during early afternoon (P < 0.001) that was inverse to leptin profiles peaking in the early night. When subjects stayed awake, the Nampt rhythm was preserved but phase advanced by about 2 h (P < 0.05). Two-hour postprandial plasma glucose concentrations were elevated after sleep loss (P < 0.05), whereas serum insulin was not affected. The relative glucose increase due to sleep loss displayed a positive association with the magnitude of the Nampt phase shift (r = 0.54; P < 0.05). CONCLUSIONS Serum Nampt concentrations follow a diurnal rhythm, peaking in the afternoon. Sleep loss induces a Nampt rhythm phase shift that is positively related to the impairment of postprandial glucose metabolism due to sleep deprivation, suggesting a regulatory impact of Nampt rhythmicity on glucose homeostasis.
Therapeutic targeting of N‐cadherin is an effective treatment for multiple myeloma

Elevated expression of the cell adhesion molecule N‐cadherin (cadherin 2, type 1, N‐cadherin (neuronal); CDH2) is associated with poor prognosis in newly‐diagnosed multiple myeloma (MM) patients. In this study, we investigated whether targeting of N‐cadherin represents a potential treatment for the ~50% of MM patients with elevated N‐cadherin. Initially, we stably knocked‐down N‐cadherin in the mouse MM plasma cell (PC) line 5TGM1 to assess the functional role of N‐cadherin in MM pathogenesis. When compared with 5TGM1‐scramble‐shRNA cells, 5TGM1‐Cdh2‐shRNA cells had significantly reduced adhesion to bone marrow endothelial cells. However, N‐cadherin knock‐down did not affect 5TGM1 cell proliferation or adhesion to bone marrow stromal cells. In the C57BL/KaLwRij murine MM model, mice intravenously inoculated with 5TGM1‐Cdh2‐shRNA cells showed significantly decreased tumour burden after 4 weeks, compared with animals bearing 5TGM1‐scramble‐shRNA cells. Finally, the N‐cadherin antagonist ADH‐1 had no effect on tumour burden in the established disease setting, whereas up‐front ADH‐1 treatment resulted in significantly reduced tumour burden after 4 weeks. Our findings demonstrate that N‐cadherin may play a key role in the extravasation of circulating MM PCs promoting bone marrow homing. Moreover, these studies suggest that N‐cadherin may represent a viable therapeutic target to prevent the dissemination of MM PCs and delay MM disease progression.
Low testosterone levels and increased inflammatory markers in patients with cancer and relationship with cachexia.

CONTEXT Male cancer patients suffer from fatigue, sexual dysfunction, and decreased functional performance and muscle mass. These symptoms are seen in men with hypogonadism and/or inflammatory conditions. However, the relative contribution of testosterone and inflammation to symptom burden in cancer has not been well-established. OBJECTIVE The aim of this study was to measure testosterone levels in male cancer patients and determine the relationship between testosterone, inflammation, and symptom burden. DESIGN/SETTING This cross-sectional study enrolled patients from a tertiary-care center. SUBJECTS/OUTCOME MEASURES: Subjects included males with cancer-cachexia (CC; n = 45) and cancer without cachexia (CNC; n = 50), as well as noncancer controls (CO; n = 45). Total testosterone (TT), bioavailable testosterone, C-reactive protein (CRP), and IL-6 were measured in plasma. Functional performance was assessed by the ECOG (Eastern Cooperative Oncology Group) and KPS (Karnofsky Performance Scales), and sexual function was assessed by the IIEF (International Index of Erectile Function). RESULTS Low testosterone levels were seen in more than 70% of CC cases. TT was lower in CC compared to CNC (P < 0.05). Also, CC had lower bioavailable testosterone, grip strength, IIEF scores, appendicular lean body mass, and fat mass and higher IL-6 and CRP compared to controls (P ≤ 0.05). ECOG and KPS were lower in CC and CNC compared to controls (P ≤ 0.05). On multiple regression analysis, TT, albumin, and CRP predicted symptoms differentially in cancer patients. CONCLUSIONS CC patients have higher inflammation and lower testosterone, grip strength, functional status, erectile function, fat mass, and appendicular lean body mass. Inflammation, TT, and albumin are associated with heavier symptom burden in this population. Interventional trials are needed to determine whether testosterone replacement and/or antiinflammatory agents benefit cancer patients.
From CLL to Multiple Myeloma ‐ Spleen Tyrosine Kinase (SYK) influences multiple myeloma cell survival and migration

Arnaud Petit Andr e Baruchel Jacqueline Clavel Benôıt Brethon Yves Bertrand Patrick Lutz Fabienne Nacka St ephane Ducassou Unit of Paediatric Haematology and Oncology, Bordeaux University Hospital, Bordeaux-Cedex, Unit of Paediatric Haematology and Oncology, Armand Trousseau Hospital, Unit of Paediatric Haematology and Immunology, Robert Debr e Hospital, Paris, Institut National de la Sant e et de la recherche M edicale (INSERM), Unit754, Registry of Malignant Hemopathies in childhood, Villejuif, Institute of Paediatric Haematology and Oncology, 1, place du Professeur Joseph Renault, Lyon, Unit of Paediatric Haematology and Oncology, Hautepierre Hospital, Strasbourg, and Clinical Investigation Centre in Paediatrics CIC 1401, Bordeaux University Hospital, Bordeaux-Cedex, France E-mail: stephane.ducassou@chu-bordeaux.fr
Anaplastic large cell lymphoma in paediatric and young adult patients

Anaplastic large cell lymphoma (ALCL) is a heterogeneous disease of debateable origin that, in children, is largely anaplastic lymphoma kinase (ALK) positive with aberrant ALK activity induced following the formation of chromosomal translocations. Whilst the survival rates for this disease are relatively high, a significant proportion (20‐40%) of patients suffer disease relapse, in some cases on multiple occasions and therefore suffer the toxic side‐effects of combination chemotherapy. Traditionally, patients are treated with a combination of agents although recent data from relapse patients have suggested that low risk patients might benefit from single agent vinblastine and, going forward, the addition of ALK inhibitors to the therapeutic regimen may have beneficial consequences. There are also a plethora of other drugs that might be advantageous to patients with ALCL and many of these have been identified through laboratory research although the decision as to which drugs to implement in trials will not be trivial.
Cognitive Development of Singletons Born After Intracytoplasmic Sperm Injection Compared With In Vitro Fertilization and Natural Conception

The techniques of maternal hormonal stimulation are similar for intracytoplasmic sperm injection (ICSI) and in vitro fertilization (IVF), and both involve fertilization in vitro. However, in contrast to IVF, ICSI involves sperm selection and oocyte penetration and thus bypasses the selection processes that occur during natural conception, raising concerns that conception by ICSI may result in altered health and development of the offspring. This prospective study compared cognitive development of 5-8-year-old singletons born after ICSI during the years 1996-1999 with matched singletons born after IVF or natural conception (NC). The observers were blinded to the mode of conception. The short form of the Revised Amsterdam Child Intelligence Test was used to measure the intelligence quotient (IQ). The unadjusted mean IQ for children conceived by ICSI (n = 83) was 3.9 points lower than that of the IVF controls (n = 82) (103 versus 107; 95% confidence interval [CI], -0.7, 8.4), and the adjusted mean IQ score was 3.6 points lower (95% CI, -0.8, 8.0). There was no difference between ICSF and IVF children in the distribution of IQ-scores ( 115: ICSI 24% versus IVF 32% [unadjusted: P =.268]). The unadjusted mean IQ score of children conceived by ICSI (n = 86) was 6.8 points lower than that of children conceived naturally (NC; n = 85)(XX versus XX; 95% CI, 2.0, 11.6); the adjusted mean IQ score was 5.6 points lower [95% CI, 0.9, 10.3] and was unaffected by additional adjustment for prematurity and other covariables (P 115: ICSI 24% versus NC 40%; 85-115: ICSI 64% versus NC 54%; and <85: ICSI 12% versus NC 6% [unadjusted, P =.019]). This small study found that IQ scores were lower in 5-8-year-old children conceived by ICSI than in children conceived by IVF or naturally. The greatest difference was between ICSI and NC children. The clinical significance of these findings is unclear.
Endometrial miR-181a and miR-98 expression is altered during transition from normal into cancerous state and target PGR, PGRMC1, CYP19A1, DDX3X, and TIMP3.

CONTEXT Evidence suggests that a number of microRNA (miRNA) are aberrantly expressed in endometrial disorders with potential posttranscriptional regulation of their specific target genes, including ovarian steroid receptors. OBJECTIVES Our objective was to assess the endometrial expression of miR-98 and miR-181a and their respective target genes, progesterone (P4) receptor membrane component 1 (PGRMC1) and P4 receptor (PGR). DESIGN, SETTING, AND PATIENTS We evaluated tissue expression and in vitro regulation at an academic university medical center in endometrial biopsies and endometrial tissues from follicular and luteal phases with and without exposure to hormonal therapies and grade I-III endometrial cancer (n = 52). INTERVENTIONS INTERVENTIONS included endometrial biopsies and in vitro transfection. MAIN OUTCOME MEASURES We evaluated expression and function of miR-98 and miR-181a. RESULTS Aberrant expression of miR-98 and miR-181a is associated with endometrial transition from normal into cancerous states, which to some extent is influenced by hormonal milieu, and exhibited an inverse relationship with PGMRC1 and PGR expression, respectively. Treatments of Ishikawa cells with 17β-estradiol, P4, or medroxyprogesterone acetate had limited effects on miR-98, miR-181a, and PGRMC1 expression, whereas 17β-estradiol treatment increased PGR expression. In Ishikawa cells, gain of function of miR-98 repressed PGRMC1 and CYP19A1, and miR-181a repressed PGR, DDX3X, and TIMP3 at mRNA and protein levels through direct interactions with their respective 3'-untranslated regions and CCNE1 through miR-181a-induced DDX3X repression, with miR-98 reducing the rate of cell proliferation as compared with controls. CONCLUSION miR-98 and miR-181a through their regulatory functions on PGRMC1, PGR, CYP19A1, TIMP3, and DDX3X expression may influence a wide range of endometrial cellular activities during normal menstrual cycle and transition into disease states, including endometrial cancer.
Elimination half-life of anti-Müllerian hormone.

CONTEXT Anti-Müllerian hormone (AMH) is a glycoprotein that is secreted by the granulosa cells in the human ovary. In the postpubertal female, circulating AMH reflects the number of follicles within the ovary. It is mandatory to know the serum elimination half-life (t(1/2)) of AMH to study in vivo short-term changes of the hormone. OBJECTIVE Our objective was to determine the kinetics of decay of AMH in the human female. PATIENTS, DESIGN, AND SETTING Premenopausal women undergoing total abdominal hysterectomy plus bilateral salpingo-oophorectomy participated in this cohort study (n = 21) at an academic tertiary referral center. INTERVENTIONS Serum samples were obtained immediately before surgery and in 12-h intervals thereafter for 8 d. MAIN OUTCOME MEASURE AMH elimination was calculated, applying a one-compartment model with first-order kinetics. RESULTS Mean preoperative AMH levels were 0.67 ng/ml (range, 0.1-1.78 ng/ml) and dropped to 0.08 ng/ml within 84 h after surgery. The AMH decay followed first-order kinetics. The mean terminal t(1/2) of AMH was calculated as 27.6 ± 0.8 h. CONCLUSION AMH elimination reaches approximately 84% after 3 d, approximately 91% after 4 d, approximately 95% after 5 d, and can be considered complete after 8 d.
How we manage persons with hereditary angioedema

Hereditary angioedema (HAE) is a rare autosomal dominant genetic disorder clinically characterized by recurrent attacks of subcutaneous and mucosal swelling that can result in significant morbidity and even mortality. Several novel therapies introduced since 2008 have dramatically transformed the approach to management. In this review we will discuss the current understanding of the pathophysiology of HAE, diagnostic evaluation of recurrent angioedema without urticaria, and the therapeutic approach to HAE. We advocate taking an integrative approach to care in order to normalize the lives of affected patients.
Alterations of circulating endothelial cell and endothelial progenitor cell counts around the ovulation.

CONTEXT Circulating endothelial cells (CECs) and progenitor cells (CEPs) have been intensively studied as a promising tool for treating ischemic diseases and monitoring cancer treatments, but how the menstrual cycle affects the variation in their counts remains unclear. OBJECTIVE The aims of the study were to determine the influence of the menstrual cycle on the number of CECs and CEPs and to investigate the association of their counts with circulating hormones and angiogenesis-associated factors. DESIGN CEP and CEC counts by flow cytometry and the CellSearch system and circulating factor levels were measured eight times during the menstrual cycle in 18 volunteers. The menstrual cycle was divided into six phases based on hormone concentrations. RESULTS CEP counts peaked in the periovulatory and middle luteal phases with a drop in the early luteal phase. CEC counts showed no significant variation. There were significant correlations between the CEP counts and the serum concentrations of estradiol (E2), LH, and granulocyte colony-stimulating factor (G-CSF) (P < 0.0001, P < 0.0001, and P = 0.01, respectively). The difference in CEP counts between two adjacent phases was significantly correlated with that in E2, LH, G-CSF, and serum vascular endothelial growth factor (P < 0.0001, P < 0.0001, P = 0.02, and P = 0.006, respectively). CONCLUSION CEP counts peaked in the periovulatory and middle luteal phases, with a drop in the early luteal phase, and were correlated with serum E2, LH, and G-CSF concentrations. Consideration of the variation in CEP counts would be important for the clinical application of CEPs.
Involvement of hypothalamus autoimmunity in patients with autoimmune hypopituitarism: role of antibodies to hypothalamic cells.

CONTEXT Antipituitary antibodies (APA) but not antihypothalamus antibodies (AHA) are usually searched for in autoimmune hypopituitarism. OBJECTIVE Our objective was to search for AHA and characterize their hypothalamic target in patients with autoimmune hypopituitarism to clarify, on the basis of the cells stained by these antibodies, the occurrence of autoimmune subclinical/clinical central diabetes insipidus (CDI) and/or possible joint hypothalamic contribution to their hypopituitarism. DESIGN We conducted a cross-sectional cohort study. PATIENTS Ninety-five APA-positive patients with autoimmune hypopituitarism, 60 without (group 1) and 35 with (group 2) lymphocytic hypophysitis, were studied in comparison with 20 patients with postsurgical hypopituitarism and 50 normal subjects. MAIN OUTCOME MEASURES AHA by immunofluorescence and posterior pituitary function were evaluated; then AHA-positive sera were retested by double immunofluorescence to identify the hypothalamic cells targeted by AHA. RESULTS AHA were detected at high titer in 12 patients in group 1 and in eight patients in group 2. They immunostained arginine vasopressin (AVP)-secreting cells in nine of 12 in group 1 and in four of eight in group 2. All AVP cell antibody-positive patients presented with subclinical/clinical CDI; in contrast, four patients with GH/ACTH deficiency but with APA staining only GH-secreting cells showed AHA targeting CRH- secreting cells. CONCLUSION The occurrence of CDI in patients with lymphocytic hypophysitis seems due to an autoimmune hypothalamic involvement rather than an expansion of the pituitary inflammatory process. To search for AVP antibody in these patients may help to identify those of them prone to develop an autoimmune CDI. The detection of AHA targeting CRH-secreting cells in some patients with GH/ACTH deficiency but with APA targeting only GH-secreting cells indicates that an autoimmune aggression to hypothalamus is jointly responsible for their hypopituitarism.
Mutual interactions between depression/quality of life and adherence to a multidisciplinary lifestyle intervention in obesity.

CONTEXT There is scarce knowledge of the interaction between depression/health-related quality of life (HRQOL) and lifestyle intervention in obesity. OBJECTIVE The aim of the study was to establish whether baseline mood status or HRQOL affects attendance to educational or exercise sessions and whether attendance to these two components of the intervention affects mood and/or HRQOL in obesity. DESIGN A total of 282 overweight/obese subjects (body mass index, 33.4 ± 5.9 kg/m(2); 103 males, 179 females; age, 53.8 ± 13.0 yr, mean ± sd) were consecutively enrolled in a multidisciplinary lifestyle intervention program. During the intensive phase of the intervention (3 months) patients were invited to attend eight educational sessions and 26 exercise group sessions. RESULTS Poor adherence to exercise sessions is predicted by baseline depressive mood (P =0.006) and by low levels of HRQOL (domains of Vitality, Physical Role Functioning, Social Functioning, Mental Composite, Physical Composite Scores) (P < 0.05). Attendance to the educational sessions is associated with beneficial effects of the lifestyle intervention on depressive symptoms (P < 0.013) and on several mental domains of HRQOL (P < 0.041); attendance to the exercise sessions predicted the beneficial effects on perceived general health (P < 0.021) and body mass index (P < 0.011). Attendance to both educational and exercise components is associated (P < 0.05) with the reductions in waist circumference, fat mass, and blood pressure observed after the intensive phase of the intervention. CONCLUSIONS Measurement of depressive mood and HRQOL before lifestyle intervention allows identification of patients at increased risk of attrition with exercise and educational sessions. Both the exercise and the educational sessions are essential for gaining the full spectrum of psychological and clinical benefits from multidisciplinary lifestyle intervention in obesity.
A Woman With Spontaneous Focal Muscle Movements

The present case is about a patient who had rolling muscle contractions, whichwere electrically silent. She was diagnosed as having Rippling Muscle Disease, in her case; this disorder was likely autoimmune associated. RMD can be hereditary, acquired due to de novo mutations, or have autoimmune etiology. Most of the time RMD is associated with myasthenia gravis. Depending of the form of RMD, patients respond to dantrolene and/or immunossupresants.
Guidelines for screening and management of late and long‐term consequences of myeloma and its treatment

A growing population of long‐term survivors of myeloma is now accumulating the ‘late effects’ not only of myeloma itself, but also of several lines of treatment given throughout the course of the disease. It is thus important to recognise the cumulative burden of the disease and treatment‐related toxicity in both the stable and active phases of myeloma, some of which is unlikely to be detected by routine monitoring. We summarise here the evidence for the key late effects in long‐term survivors of myeloma, including physical and psychosocial consequences (in Parts 1 and 2 respectively), and recommend the use of late‐effects screening protocols in detection and intervention. The early recognition of late effects and effective management strategies should lead to an improvement in the management of myeloma patients, although evidence in this area is currently limited and further research is warranted.
Zone II Flexor Tendon Therapy: Mobilize or Immobilize?

This study investigated the postoperative management approaches used in the treatment of flexor tendon repairs in Zone II of the hand. The therapists and the hand surgeons who treat patients with acute hand injuries in the Metropolitan Toronto area were surveyed to detect their current practice trends and preferences in flexor tendon postoperative management. The survey focused on the following four protocols: 1. immobilization for at least three weeks, 2. the Kleinert program of controlled active motion, 3. the Duran program of controlled passive motion, and 4. combination of controlled active and passive motion. Although the results suggested that mobilization is the preferred postoperative management amongst the majority of responding therapists and hand surgeons, the type of mobilization program preferred differed. The therapists demonstrated a trend towards a combination of early controlled active and passive motion; whereas, the trend amongst the surgeons was that of early controlled active motion. The decision to use one specific management approach over another was found to be very “patient specific”. As well, a wide variation on the preferences given for the splinting positions at the wrist, metacarpalphalangeal (MCP) joint, and the proximal interphalangeal (PIP) joint was noted.