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The gastrointestinal tract plays a role in the development and treatment of metabolic diseases. During a meal, the gut provides crucial information to the brain regarding incoming nutrients to allow proper maintenance of energy and glucose homeostasis. This gut–brain communication is regulated by various peptides or hormones that are secreted from the gut in response to nutrients; these signaling molecules can enter the circulation and act directly on the brain, or they can act indirectly via paracrine action on local vagal and spinal afferent neurons that innervate the gut. In addition, the enteric nervous system can act as a relay from the gut to the brain. The current review will outline the different gut–brain signaling mechanisms that contribute to metabolic homeostasis, highlighting the recent advances in understanding these complex hormonal and neural pathways. Furthermore, the impact of the gut microbiota on various components of the gut–brain axis that regulates energy and glucose homeostasis will be discussed. A better understanding of the gut–brain axis and its complex relationship with the gut microbiome is crucial for the development of successful pharmacological therapies to combat obesity and diabetes.

The gastrointestinal tract plays a role in the development and treatment of metabolic diseases. During a meal, the gut provides crucial information to the brain regarding incoming nutrients to allow proper maintenance of energy and glucose homeostasis. This gut-brain communication is regulated by various peptides or hormones that are secreted from the gut in response to nutrients; these signaling molecules can enter the circulation and act directly on the brain, or they can act indirectly via paracrine action on local vagal and spinal afferent neurons that innervate the gut. In addition, the enteric nervous system can act as a relay from the gut to the brain. The current review will outline the different gut-brain signaling mechanisms that contribute to metabolic homeostasis, highlighting the recent advances in understanding these complex hormonal and neural pathways. Furthermore, the impact of the gut microbiota on various components of the gut-brain axis that regulates energy and glucose homeostasis will be discussed. A better understanding of the gut-brain axis and its complex relationship with the gut microbiome is crucial for the development of successful pharmacological therapies to combat obesity and diabetes.

Diaphragmatic function is important in treating respiratory failure. Muscle endurance has been measured using twitch electrical stimulation and accelerometer-based mechanomyography. The purpose of this study was to evaluate the reproducibility and the time to perform an endurance test on the diaphragm muscle using electrical stimulation of the phrenic nerve. Twenty healthy subjects (21.6±1.6yrs) were tested in the supine position on two separate occasions. Stimulation electrodes were placed on the left (n=18) or right (n=2) phrenic nerve underneath the sternocleidomastoid muscle. A tri-axial accelerometer was placed on the abdomen and 5 minutes of submaximal electrical stimulation at 5Hz was performed. The resultant vector of acceleration at peak and end acceleration was analyzed: endurance index = end/peak*100). The test was successfully completed 41/47 times. The endurance index for the two days was 73.8±9.4% and 72.6±11.1%, respectively. The time to find the phrenic nerve was 34.8±13.1s for the first 10 subjects and 13.0±2.8s for the second 10 subjects. For the second group, the mean difference in endurance between days was 0.03% with a 95% confidence interval of -1.6% to 1.5%. In conclusion, the diaphragm endurance test was reproducible with practice.

BACKGROUND: Bullous pemphigoid is a blistering skin disorder with increased mortality. We tested whether a strategy of starting treatment with doxycycline gives acceptable short-term blister control while conferring long-term safety advantages over starting treatment with oral corticosteroids. METHODS: We did a pragmatic, multicentre, parallel-group randomised controlled trial of adults with bullous pemphigoid (three or more blisters at two or more sites and linear basement membrane IgG or C3). Participants were randomly assigned to doxycycline (200 mg per day) or prednisolone (0·5 mg/kg per day) using random permuted blocks of randomly varying size, and stratified by baseline severity (3-9, 10-30, and >30 blisters for mild, moderate, and severe disease, respectively). Localised adjuvant potent topical corticosteroids (

Background Survival in mycosis fungoides (MF) is varied and may be poor. The PROCLIPI (PROspective Cutaneous Lymphoma International Prognostic Index) study is a web‐based data collection system for early‐stage MF with legal data‐sharing agreements permitting international collaboration in a rare cancer with complex pathology. Clinicopathological data must be 100% complete and in‐built intelligence in the database system ensures accurate staging. Objectives To develop a prognostic index for MF. Methods Predefined datasets for clinical, haematological, radiological, immunohistochemical, genotypic, treatment and quality of life are collected at first diagnosis of MF and annually to test against survival. Biobanked tissue samples are recorded within a Federated Biobank for translational studies. Results In total, 430 patients were enrolled from 29 centres in 15 countries spanning five continents. Altogether, 348 were confirmed as having early‐stage MF at central review. The majority had classical MF (81·6%) with a CD4 phenotype (88·2%). Folliculotropic MF was diagnosed in 17·8%. Most presented with stage I (IA: 49·4%; IB: 42·8%), but 7·8% presented with enlarged lymph nodes (stage IIA). A diagnostic delay between first symptom development and initial diagnosis was frequent [85·6%; median delay 36 months (interquartile range 1290)]. This highlights the difficulties in accurate diagnosis, which includes lack of a singular diagnostic test for MF. Conclusions This confirmed early‐stage MF cohort is being followed‐up to identify prognostic factors, which may allow better management and improve survival by identifying patients at risk of disease progression. This study design is a useful model for collaboration in other rare diseases, especially where pathological diagnosis can be complex.