The activating mutation R201C in GNAS promotes intestinal tumourigenesis in Apc(Min/+) mice through activation of Wnt and ERK1/2 MAPK pathways.

Somatically acquired, activating mutations of GNAS, the gene encoding the stimulatory G-protein Gsalpha subunit, have been identified in kidney, thyroid, pituitary, leydig cell, adrenocortical and, more recently, in colorectal tumours, suggesting that mutations such as R201C may be oncogenic in these tissues. To study the role of GNAS in intestinal tumourigenesis, we placed GNAS R201C under the control of the A33-antigen promoter (Gpa33), which is almost exclusively expressed in the intestines. The GNAS R201C mutation has been shown to result in the constitutive activation of Gsalpha and adenylate cyclase and to lead to the autonomous synthesis of cyclic adenosine monophosphate (cAMP). Gpa33(tm1(GnasR201C)Wtsi/+) mice showed significantly elevated cAMP levels and a compensatory upregulation of cAMP-specific phosphodiesterases in the intestinal epithelium. GNAS R201C alone was not sufficient to induce tumourigenesis by 12 months, but there was a significant increase in adenoma formation when Gpa33(tm1(GnasR201C)Wtsi/+) mice were bred onto an Apc(Min/+) background. GNAS R201C expression was associated with elevated expression of Wnt and extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase (ERK1/2 MAPK) pathway target genes, increased phosphorylation of ERK1/2 MAPK and increased immunostaining for the proliferation marker Ki67. Furthermore, the effects of GNAS R201C on the Wnt pathway were additive to the inactivation of Apc. Our data strongly suggest that activating mutations of GNAS cooperate with inactivation of APC and are likely to contribute to colorectal tumourigenesis

Conventional and complementary health care use and out-of-pocket expenses among Australians with a self-reported mental health diagnosis: a cross-sectional survey.

BACKGROUND: Mental health disorders are a global health concern. In Australia, numerous national reports have found that the current mental healthcare system does not adequately meet the needs of Australians with mental illness. Consequently, a greater understanding of how people with a mental health disorder are using the broader healthcare system is needed. The aim of this paper is to explore conventional and complementary health care use and expenditure among Australian adults reporting a mental health disorder diagnosis. METHODS: A cross-sectional online survey of 2,019 Australian adults examined socio-demographic characteristics, complementary and conventional health care use and the health status of participants. RESULTS: 32 % (n = 641) of the total sample (N = 2019) reported a mental health disorder in the previous 3 years. Of these, 96 % reported consulting a general practitioner, 90.6 % reported using prescription medicines, 42.4 % consulted a complementary medicine practitioner, 56.9 % used a complementary medicine product and 23 % used a complementary medicine practice. The estimated 12-month out-of-pocket health care expenditure among Australians with a mental health disorder was AUD$4,568,267,421 (US$ 3,398,293,672) for conventional health care practitioners and medicines, and AUD$1,183,752,486 (US$ 880,729,891) for complementary medicine practitioners, products and practices. Older people (50-59 and 60 and over) were less likely to consult a CM practitioner (OR = 0.538, 95% CI [0.373, 0.775]; OR = 0.398, 95% CI [0.273, 0.581] respectively) or a psychologist/counsellor (OR = 0.394, 95% CI [0.243, 0.639]; OR = 0.267, 95% CI [0.160, 0.447] respectively). People either looking for work or not in the workforce were less likely to visit a CM practitioner (OR = 0.298, 95% CI [0.194, 0.458]; OR = 0.476, 95% CI [0.353, 0.642], respectively). CONCLUSIONS: A substantial proportion of Australian adults living with a mental health disorder pay for both complementary and conventional health care directly out-of-pocket. This finding suggests improved coordination of healthcare services is needed for individuals living with a mental health disorder. Research examining the redesign of primary health care provision should also consider whether complementary medicine practitioners and/or integrative health care service delivery models could play a role in addressing risks associated with complementary medicine use and the unmet needs of people living with a mental health disorder

Chlamydia trachomatis Biovar L2 Infection in Women in South Africa

We detected Chlamydia trachomatis biovar L2 in vaginal swab specimens of 7 women with vaginal discharge in South Africa. Whole-genome sequencing directly from clinical specimens identified a closely related cluster of strains. The clinical role of this infection in the context of syndromic management should be clarified

Impact of a brief psychological intervention on lifestyle, risk factors and disease knowledge during phase I of cardiac rehabilitation after acute coronary syndrome

Introduction:This study examined the efficacy of a brief inpatient psychoeducational intervention on knowledge about acute coronary syndromes (ACS), control of risk factors, and adaptive health habits and lifestyle. The intervention was intended to facilitate rehabilitation after ACS and its short- and medium-term impact was assessed. Methods: One hundred and twenty-one patients with ACS, admitted to a central cardiology unit in Portugal, were randomized to an experimental group (EG, n=65) or a control group (CG, n=56). We used the Portuguese versions of the Knowledge Questionnaire and the Health Habits Questionnaire. Patients were assessed at hospital admission, hospital discharge and one- and two-month follow-up. Results: The intervention had a significant impact, increasing knowledge about ACS (F=500.834; p=0.000) in the EG, which was maintained at two-month follow-up, and changing health habits at two-month follow-up (F=218.129; p=0.000). The CG demonstrated decreased knowledge (F=3.368; p=0.069) during the same period. Conclusions: A brief inpatient psychoeducational intervention has a positive effect on knowledge about ACS, risk factor control and promotion of positive health habits, and is effective in improving cardiac rehabilitation

An aerosol challenge model of tuberculosis in Mauritian cynomolgus macaques

Background New interventions for tuberculosis are urgently needed. Non-human primate (NHP) models provide the most relevant pre-clinical models of human disease and play a critical role in vaccine development. Models utilising Asian cynomolgus macaque populations are well established but the restricted genetic diversity of the Mauritian cynomolgus macaques may be of added value. Methods Mauritian cynomolgus macaques were exposed to a range of doses of M. tuberculosis delivered by aerosol, and the outcome was assessed using clinical, imaging and pathology-based measures. Results All macaques developed characteristic clinical signs and disease features of tuberculosis (TB). Disease burden and the ability to control disease were dependent on exposure dose. Mauritian cynomolgus macaques showed less variation in pulmonary disease burden and total gross pathology scores within exposure dose groups than either Indian rhesus macaques or Chinese cynomolgus macaques Conclusions The genetic homogeneity of Mauritian cynomolgus macaques makes them a potentially useful model of human tuberculosis

A comparison of medium-term heat acclimation by post-exercise hot water immersion or exercise in the heat: Adaptations, overreaching, and thyroid hormones.

This research compared thermal and perceptual adaptations, endurance capacity, and overreaching markers in men after 3, 6, and 12-days of post-exercise hot water immersion (HWI) or exercise heat acclimation (EHA) with a temperate exercise control (CON), and examined thyroid hormones as a mechanism for the reduction in resting and exercising core temperature (Tre) after HWI. HWI involved a treadmill run at 65% V̇O2peak in 19°C followed by a 40°C bath. EHA and CON involved a work-matched treadmill run at 65% V̇O2peak in 33°C or 19°C, respectively. Compared with CON, resting mean body temperature (Tb), resting and end-exercise Tre, Tre at sweating onset, thermal sensation and perceived exertion were lower and whole-body sweat rate (WBSR) was higher after 12-days of HWI (all P ≤ 0.049, resting Tb: CON -0.11 ± 0.15°C, HWI -0.41 ± 0.15°C). Moreover, resting Tb and Tre at sweating onset were lower after HWI than EHA (P ≤ 0.015, resting Tb: EHA -0.14 ± 0.14°C). No differences were identified between EHA and CON (P ≥ 0.157) except WBSR which was greater after EHA (P = 0.013). No differences were observed between interventions for endurance capacity or overreaching markers (mood, sleep, Stroop, P ≥ 0.190). Thermal adaptations observed after HWI were not related to changes in thyroid hormone concentrations (P ≥ 0.086). In conclusion, 12-days of post-exercise hot water immersion conferred more complete heat acclimation than exercise heat acclimation without increasing overreaching risk, and changes in thyroid hormones are not related to thermal adaptationsafter post-exercise hot water immersion

Superconducting nanowire photon number resolving detector at telecom wavelength

The optical-to-electrical conversion, which is the basis of optical detectors, can be linear or nonlinear. When high sensitivities are needed single-photon detectors (SPDs) are used, which operate in a strongly nonlinear mode, their response being independent of the photon number. Nevertheless, photon-number resolving (PNR) detectors are needed, particularly in quantum optics, where n-photon states are routinely produced. In quantum communication, the PNR functionality is key to many protocols for establishing, swapping and measuring entanglement, and can be used to detect photon-number-splitting attacks. A linear detector with single-photon sensitivity can also be used for measuring a temporal waveform at extremely low light levels, e.g. in long-distance optical communications, fluorescence spectroscopy, optical time-domain reflectometry. We demonstrate here a PNR detector based on parallel superconducting nanowires and capable of counting up to 4 photons at telecommunication wavelengths, with ultralow dark count rate and high counting frequency

Core Depressive Symptoms In Depressed Cancer OutpatientsB

Objective: This study aimed to estimate the prevalence of core depressive symptoms among cancer outpatients diagnosed with depressive or adjustment disorders with depressed mood. We also aimed to detect potential differences between patient self-assessment and psychiatrist evaluation in classifying the severity of depression. Methods: Fifty-two outpatients diagnosed with solid tumor malignancy and depressive or adjustment disorder with depressed mood were assessed using the Hamilton Depression Rating Scale (HAMD-17) (and its shortened version the HAMD-7) and the Zung Self-Rating Depression Scale (ZSDS) (and its shortened version BZSDS). Results: Based on HAMD-7 results, the prevalence of moderate depression was low (7.7%); using the BZSDS moderate depression was absent. Mild depression was identified in 82.3% and 73% of our subjects using the HAMD-7 and the BZSDS, respectively. The strength of agreement between psychiatrist and patients' self-evaluation for mild depression was "slight", employing the original and the abbreviated versions of both scales. Conclusion: Our findings suggest that the prevalence of core depressive symptoms is very low in cancer patients diagnosed with depressive disorder. The lack of a strong agreement between psychiatrist and patient in classifying the severity of depression highlights the importance of factors such as well-being and functional status among depressed cancer patients in their self assessment of depression. © Massimo et al