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CONTEXT: Little accurate information is available regarding the risk of hypopituitarism after irradiation of skull base meningiomas. DESIGN: Retrospective study in a single centre. PATIENTS: 48 patients with a skull base meningioma and normal pituitary function at diagnosis, treated with radiotherapy (RXT) between 1998 and 2017 (median follow-up of 90 months). MEASUREMENTS: The GH, TSH, LH/FSH and ACTH hormonal axes were evaluated yearly for the entire follow-up period. Mean doses delivered to the pituitary gland (PitD) and the hypothalamus (HypoD) were calculated, as well as the doses responsible for the development of deficits in 50% of patients after 5 years (TD50). RESULTS: At least one hormone deficit was observed in 38% of irradiated patients and complete hypopituitarism in 13%. The GH (35%), TSH (32%) and LH/FSH axes (28%) were the most frequently affected, while ACTH secretion axis was less altered (13%). The risk of hypopituitarism was independently related to planning target volume (PTV) and to the PitD (threshold dose 45 Gy; TD50 between 50 and 54 Gy). In this series, the risk was less influenced by the HypoD, increasing steadily between doses of 15 and 70 Gy with no clear-cut dose threshold. CONCLUSIONS: Over a median follow-up period of 7.5 years, hypopituitarism occurred in more than one third of patients irradiated for a skull base meningioma, and this prevalence was time- and dose-dependent. In this setting, the risk of developing hypopituitarism was mainly determined by the irradiated target volume and by the dose delivered to the pituitary gland.

BACKGROUND: Glucocorticoids (GC) play a major role in muscle atrophy. As skeletal muscle is a secretory organ, characterization of the muscle secretome elicited by muscle atrophy should allow to better understand the cellular mechanisms and to identify circulating biomarkers of this condition. Our project aimed to identify the changes in the muscle secretome associated with GC-induced muscle atrophy and susceptible to translate into circulation. METHODS: We have identified the GC-induced changes in the secretome of C2 C12 muscle cells by proteomic analysis, and then, we have determined how these changes translate into the circulation of mice or human subjects exposed to high concentrations of GC. RESULTS: This approach led us to identify Serpina3n as one of the most markedly secreted protein in response to GC. Our original in vitro results were confirmed in vivo by an increased expression of Serpina3n in skeletal muscle (3.9-fold; P < 0.01) and in the serum (two-fold; P < 0.01) of mice treated with GC. We also observed increased levels of the human orthologue Serpina3 in the serum of Cushing's syndrome patients compared with healthy controls matched for age and sex (n = 9/group, 2.5-fold; P < 0.01). An increase of Serpina3n was also demonstrated in muscle atrophy models mediated by GC such as cancer cachexia (four-fold; P < 0.01), sepsis (12.5-fold; P < 0.001), or diabetes (two-fold; P < 0.01). In contrast, levels of Serpina3n both in skeletal muscle and in the circulation were reduced in several models of muscle hypertrophy induced by myostatin inhibition (P < 0.01). Furthermore, a cluster of data suggests that the regulation of muscle Serpina3n involves mTOR, an essential determinant of the muscle cell size. CONCLUSIONS: Taken together, these data suggest that Serpina3n may represent a circulating biomarker of muscle atrophy associated to GC and, broadly, a reflection of dynamic changes in muscle mass.

SUMMARYBackground Glucose sensors, such as FreeStyle® Libre, are innovative medical devices developed for diabetes patients as a replacement for classic glucose meters, ensuring continuous glucose monitoring without the disadvantage of regular skin finger pricks. Objectives To report several cases of allergic contact dermatitis caused by FreeStyle® Libre, and to report on isobornyl acrylate as a culprit allergen. Patients and Methods Fifteen patients presented with allergic contact dermatitis caused by FreeStyle® Libre. All but 1 were patch tested with a baseline series, and with pieces and/or ultrasonic bath extracts of (the adhesive part of) the glucose sensor. Isobornyl acrylate was patch tested, in various concentrations and vehicles, in 13 patients. Gas chromatography–mass spectrometry (GC-MS) of the sensors was performed. Results All patients reacted to the adhesive part of the sensor, and 12 patients were shown to be sensitized to isobornyl acrylate. Simultaneous reactions to other allergens were rarely observed. GC-MS showed the presence of isobornyl acrylate in the sensors. Conclusions Cases of allergic contact dermatitis caused by FreeStyle® Libre are increasingly being observed, and isobornyl acrylate is a relevant culprit allergen. Cross-reactivity to other acrylates was infrequently observed, but other, hitherto unidentified, contact allergens may still be present in the device.

Background Isolated maternal hypothyroxinaemia (IH) is defined as low maternal FT4 (

Newcomer and immigrant clients with limited language abilities face communication barriers that can compromise their capacity to make informed decisions about themselves and their children with serious implications for their families. These clients most likely had high proficiency of language in their country of origin but are learning the language of the new host country. Using a phenomenological design to elicit descriptions from and interpret experiences of Canadian-helping professionals, we conducted four focus groups first with child protection workers, and second with violence against women service providers. Analyses of these data uncovered five themes: (1) enhancing client engagement and self-agency; (2) advantages and drawbacks in use of interpreters; (3) creative and intensive translation strategies; (4) structural challenges and (5) gender and cultural considerations. Results are organized into an ecological framework in putting forward implications for policy and practice. The over-arching finding supports that important training and preparation are necessary for service providers to deliver language-sensitive services. As well, funding levels need to be increased to better match service delivery goals. Newcomer and immigrant clients whose language needs are not adequately met potentially face safety issues and/or fragmentation of their families.

This paper reports on a qualitative study that used focus groups to gather data from the perspective of child protection workers on their experiences in providing services to clients with limited English proficiency (LEP). The goals of the study were to understand processes of relationship building and service provision that could contribute to improved practice. Focus groups are ideal in obtaining data on how a group deals with particular situations and for understanding their decision-making processes. Measures to ensure rigour and trustworthiness were taken throughout the study. Findings provide rich and multilayered insights into the complexity of providing services for families with LEP showing that agencies use bilingual workers as well as interpreters for services. Participants noted, however, that services continued to be inconsistent with unclear guidelines and training about how and when to access interpreters. Lack of training for bilingual workers was also identified. Confidentiality issues, barriers to engaging with clients, problems with the quality of interpretation and role confusion together with benefits including interpreters being cultural and language ‘conduits’ and links to culturally specific services; enhanced communication decreasing the possibility of inaccurate assessments and lessening power differentials; and help with workload were noted.

INTRODUCTION: An increased prevalence of metabolic disorders and cardiovascular (CV) disease has been reported in childhood acute lymphoblastic leukaemia (ALL) / Non-Hodgkin lymphoma (NHL) cancer survivors. OBJECTIVE: To characterize the determinants of insulin resistance (IR) observed in this population, according to the treatment received. METHODS: 91 patients (45 men, mean age: 24 ± 5 years; mean follow-up: 15 ± 5 years) previously treated for a childhood ALL (n=76) or NHL (n=15) were grouped according to their previous treatment: chemotherapy only (Group I; n=43), chemotherapy + cranial irradiation (CI) (Group II; n=32) and chemotherapy + bone marrow transplant (BMT) / total body irradiation (TBI) (Group III, n=16). RESULTS: A high prevalence of IR (HOMA-S < 60%) was observed in the BMT/TBI group (88%) compared to groups I (9%) and II (16%). The IR patients from groups [I+II] (12% of these groups) showed higher BMI, fat mass (FM) and visceral fat when compared with the non-IR patients. In contrast, the IR patients from group III had mean BMI and total FM similar to those of non-IR patients but showed a reduction of lean body mass and an increase in the relative proportion of trunk FM similar to the IR patients from groups [I+II]. This was associated with an altered lipid profile, high TNF-α and IL-6 levels, and reduced adiponectin levels compared to IR patients from group [I+II] and non-IR patients. CONCLUSION: Childhood ALL/NHL survivors treated by BMT/TBI frequently develop severe insulin resistance associated with peripheral-to-central fat redistribution, rather than increased total FM, and low adiponectin levels which may contribute to their increased CV risk. © 2012 Blackwell Publishing Ltd.

Ethno‐racial minority families who come in contact with child protection services face unique challenges that include different ideas about appropriate child rearing practices, possibly different definitions of child maltreatment, the possibility of racial biases and service provision that does not address their particular needs. Ethno‐racial minority immigrants encounter additional barriers to services associated with the challenges of settlement in a new cultural environment. Although considerable research has explored these issues, knowledge of the experiences of ethno‐racial families who have been in contact with child protection is limited. The current paper provides insights from a qualitative study that explored the experiences of one ethno‐racial group (South Asians) in Canada. Findings suggest a variety of reasons that families come into contact with the child protection system, and the characteristics of the sample highlight their difficult financial and employment circumstances. Themes include participants' desire to be better informed about the reasons for child protection involvement and about what they can expect from the worker and the agency. They also identified a wish for services that not only recognize their cultural diversity but also respond to the needs of the whole family. In‐home services were especially appreciated. The findings reveal the resilience and personal agency among participants that can be enhanced through strength‐based approaches to practice. Helping others, establishing community networks and developing needed services were avenues of resilience identified.

BACKGROUND: When a sham operation is performed 6 h before partial hepatectomy (PH), the regenerative response is accelerated suggesting that sham operation itself contributes to cellular events leading to proliferation. MATERIALS AND METHODS: In order to examine the mechanisms implicated in this acceleration, we compared the activation of several factors associated with the progression through the cell cycle at various times after PH and after PH preceded by sham operation (S6 h + PH). The effect of a single sham (S) and two combined sham operations (S6 h + S) was also examined. Nonoperated rats were used as controls (C). RESULTS: The early factors NF-kappaB and Stat3 were activated after S6 h + PH and S6 h + S. C-jun expression was increased 0.5 h and 2 h after PH and 6 h after sham. There was no further increase in S6 h + PH and S6 h + S. In contrast, c-myc expression returned to baseline levels after S6 h and a new increase was observed 2 h after S6 h + PH but not after S6 h + S. P53 mRNA was significantly expressed 6 h after S6 h + PH, but at a level similar than that observed 6 and 12 h after PH alone. An earlier increase in c-Ha-ras mRNA and cyclin E protein was found in S6 h + PH, in comparison with PH alone. CONCLUSIONS: The first divergent response between the two combined models involved c-myc expression. However, major differences related to the accelerated liver regenerative response observed after S6 h + PH were found at late time points associating an earlier expression of c-Ha-ras and nuclear cyclin E.

Adult hypopituitary patients with growth hormone deficiency (GHD) show a significant decrease in bone mass and an increased fracture rate. Replacement therapy with GH increases bone turnover. Most of the long-term data on bone mineral content (BMC) and bone mineral density (BMD) have been acquired in open, noncontrolled trials involving limited numbers of patients. To determine whether long-term GH therapy is beneficial for bone despite the increased bone turnover, 100 patients (59 men and 41 women), aged 25-65 years (mean, 49.7 years) with adult-onset GHD were randomized to treatment with GH (40 men and 28 women; mean dose, 0.18 IU/kg per week) or to a nontreated control group (19 men and 13 women) for 24 months. Despite a similar increase in parameters of bone turnover (osteocalcin [OC], procollagen type I carboxy-terminal propeptide [PICP], and pyridinolines ([PYD]) in male and female GH-treated patients compared with controls, the effects on BMC and BMD as evaluated by dual-energy X-ray absorptiometry were gender specific. A significant increase in spine BMC and BMD and total hip BMD and a decrease in BMD at the ultradistal radius over time was observed in male GH-treated patients compared with the evolution in controls (mean +/- SEM change at 24 months: +6.8 +/- 1.1% and p = 0.009, +5.1 +/- 0.8% and p = 0.005, +3.5 +/- 0.7% and p = 0.02, and -2.6 +/- 0.8% and p = 0.008, respectively). No significant treatment effects were observed in female patients. Despite the increase in the total remodeling space induced by GH treatment, prolonged GH therapy in adult-onset GHD has a positive effect on bone balance, maintaining bone mass in women, and even increasing it in men over a 2 year-period.

While the pituitary galanin gene is highly responsive to oestrogen stimulation in vivo, in vitro effects of oestrogens on pituitary galanin gene expression have been less studied. We therefore examined the short-term effects of 17beta-oestradiol on galanin synthesis by dispersed rat anterior pituitary cell cultures and investigated the mechanisms by which oestrogens may modulate galanin gene expression. 17beta-oestradiol increased galanin mRNA expression in a dose-dependent manner, with a maximal increase observed at a concentration of 10-7 M. The 17beta-oestradiol (10-7 M)-induced increase in galanin mRNA expression varied from 3- to 20-fold (average 12-fold) depending upon the experiments and was also time-dependent, reaching significance after 6 h. A 1-h exposure of anterior pituitary cells to 17beta-oestradiol was sufficient to induce markedly galanin mRNA expression after 24 h (by 16-fold) and 48 h (by 25-fold). Tamoxifen administered simultaneously with or following 17beta-oestradiol treatment completely abolished the oestrogen-induced increase of galanin mRNA levels. Cycloheximide (10 microg/ml), a protein synthesis inhibitor, also blocked 17beta-oestradiol-induced galanin gene expression. Using transcription blockade by actinomycin D, we observed similar decreases of pituitary galanin mRNA concentrations, in the presence and absence of 17beta-oestradiol, implying no oestrogen effect on mRNA stability. We conclude that oestrogens stimulate rat pituitary galanin gene expression, mainly through a transcriptional mechanism, and that this effect requires persistent binding of the hormone to its nuclear receptor and newly synthesized protein intermediates.

Dietary zinc-deficiency induces a striking reduction and a cyclic pattern of food intake in rodents. To elucidate the mechanisms for these effects, we studied the hypothalamic content, synthesis, and distribution of galanin (GAL) and neuropeptide Y (NPY) during zinc deficiency and refeeding in the rat. In Wistar rats, three weeks of zinc-deprivation consistently induced a reduction and a cyclic pattern of night- and day-time food intake, as well as of water intake. This was accompanied in zinc-deficient (ZD) rats, and to a lesser extent in pair-fed (PF) rats, by a decrease of hypothalamic GAL mRNA concentration (CTR: 100 +/- 8, ZD: 61 +/- 4, PF: 78 +/- 2 arbitrary densitometric units, ADU, P < 0.01) and an increase of hypothalamic NPY (CTR: 100 +/- 11, ZD: 154 +/- 10, PF: 126 +/- 4 ADU, P < 0.05), without peptide modification. The two neuropeptidergic systems were not affected by the cycles of feeding, with the exception of the NPY-immunoreactivity in the suprachiasmatic nuclei (geniculo-hypothalamic tract), that was inversely correlated to the food intake in both ZD and PF animals. In a second experiment, we showed that zinc-repletion for 4 days suppressed the behaviour induced by a two-week zinc-deprivation, and reversed the increase of NPY mRNA in ZD animals. We finally demonstrated that zinc-deficiency induced a similar behaviour in Zucker rats. However, in these rats whose synthesis of NPY is constitutively up-regulated, no change of NPY synthesis was observed in ZD rats, suggesting that the increase observed in Wistar is adaptative rather than instrumental to the abnormal food intake. In conclusion, we have further characterized the cyclic feeding behaviour of the zinc-deficient Wistar rats, and shown in these animals a decreased activity of the GAL system and an increased activity of the NPY system, likely corresponding to a compensatory response of the two neuropeptidergic systems, as observed in food-deprived animals. As spontaneous food intake of ZD rats does not increase, a resistance to NPY could also be present. These behavioural and neuropeptidergic changes were partially reversed by reintroduction of zinc in the diet. In Zucker rats, the same behaviour occurred despite an insensitivity of the NPY system to the zinc-deficiency. In addition, we describe a nutritional regulation of the NPY-immunoreactivity in the geniculo-hypothalamic tract, that could constitute the substrate of circadian rhythm modulation by timed feeding.

To further investigate how sex steroids regulate galanin (GAL) in the rat pituitary and hypothalamus, we examined the effects of prepubertal gonadectomy (Gx) and long-term (9 weeks) replacement with estradiol (E2) or testosterone (T) on pituitary and hypothalamic GAL concentrations in Wistar rats (5-6/group). Sham-operated animals served as controls (CTR). Pituitary GAL concentration was markedly higher in random-cycling CTR-females than in CTR-males (1391 +/- 247 vs 39 +/- 5 pg/mg protein, P < 0.01) and decreased after Gx only in females (20 +/- 3 pg/mg protein, P < 0.01). E2 strongly increased pituitary GAL in Gx-females and Gx-males (4470 +/- 365 and 3853 +/- 347 pg/mg protein, P < 0.01), whereas T had no effect. Inversely, hypothalamic GAL was higher in CTR males than in CTR females (5.4 +/- 0.3 vs 4.0 +/- 0.5 ng/mg protein, P < 0.05), and decreased significantly after gonadectomy in males (3.7 +/- 0.2 ng/mg protein, P < 0.01). The only steroid treatment that significantly modified hypothalamic GAL in Gx animals was administration of E2 to females (5.7 +/- 0.4 ng/mg protein, P < 0.01 vs non-treated Gx). We also studied in hypophysectomized (Hx) rats (8/group) the effects of sex steroids on hypothalamic GAL concentration and distribution. The low hypothalamic GAL concentration observed in male and female Hx rats (1.0 +/- 0.1 ng/mg protein) was significantly increased by T in males and in females (respectively, by 40% and by 50%, P < 0.02) and by E2 in males (by 60%, P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)