Human β-Cell Proliferation and Intracellular Signaling: Driving in the Dark Without a Road Map

A major goal in diabetes research is to find ways to enhance the mass and function of insulin secreting β-cells in the endocrine pancreas to prevent and/or delay the onset or even reverse overt diabetes. In this Perspectives in Diabetes article, we highlight the contrast between the relatively large body of information that is available in regard to signaling pathways, proteins, and mechanisms that together provide a road map for efforts to regenerate β-cells in rodents versus the scant information in human β-cells. To reverse the state of ignorance regarding human β-cell signaling, we suggest a series of questions for consideration by the scientific community to construct a human β-cell proliferation road map. The hope is that the knowledge from the new studies will allow the community to move faster towards developing therapeutic approaches to enhance human β-cell mass in the long-term goal of preventing and/or curing type 1 and type 2 diabetes

XMMSL2 J144605.0+685735: a slow tidal disruption event

Aims. We investigate the evolution of X-ray selected tidal disruption events. Methods. New events are found in near real-time data from XMM-Newton slews, and are monitored by multi-wavelength facilities. Results. In August 2016, X-ray emission was detected from the galaxy XMMSL2 J144605.0+685735 (also known as 2MASX 14460522+6857311), that was 20 times higher than an upper limit from 25 years earlier. The X-ray flux was flat for ∼100 days and then fell by a factor of 100 over the following 500 days. The UV flux was stable for the first 400 days before fading by a magnitude, while the optical (U,B,V) bands were roughly constant for 850 days. Optically, the galaxy appears to be quiescent, at a distance of 127 ± 4 Mpc (z = 0.029 ± 0.001) with a spectrum consisting of a young stellar population of 1–5 Gyr in age, an older population, and a total stellar mass of ∼6 × 109 M⊙. The bolometric luminosity peaked at Lbol ∼ 1043 ergs s−1 with an X-ray spectrum that may be modelled by a power law of Γ ∼ 2.6 or Comptonisation of a low-temperature thermal component by thermal electrons. We consider a tidal disruption event to be the most likely cause of the flare. Radio emission was absent in this event down to < 10 μJy, which limits the total energy of a hypothetical off-axis jet to E <  5 × 1050 ergs. The independent behaviour of the optical, UV, and X-ray light curves challenges models where the UV emission is produced by reprocessing of thermal nuclear emission or by stream-stream collisions. We suggest that the observed UV emission may have been produced from a truncated accretion disc and the X-rays from Compton upscattering of these disc photons

The association of elevated blood pressure during ischaemic exercise with sport performance in Master athletes with and without morbidity

Background: An exaggerated exercise blood pressure (BP) is associated with a reduced exercise capacity. However, its connection to physical performance during competition is unknown. Aim: To examine BP responses to ischaemic handgrip exercise in Master athletes (MA) with and without underlying morbidities and to assess their association with athletic performance during the World Master Track Cycling Championships 2019. Methods: Forty-eight Master cyclists [age 59 ± 13yrs; weekly training volume 10.4 ± 4.1 h/week; handgrip maximum voluntary contraction (MVC) 46.3 ± 11.5 kg] divided into 2 matched groups (24 healthy MA and 24 MA with morbidity) and 10 healthy middle-aged non-athlete controls (age 48.3 ± 8.3 years; MVC 40.4 ± 14.8 kg) performed 5 min of forearm occlusion including 1 min handgrip isometric contraction (40%MVC) followed by 5 min recovery. Continuous beat-by-beat BP was recorded using finger plethysmography. Age-graded performance (AGP) was calculated to compare race performances among MA. Healthy Master cyclists were further grouped into middle-age (age 46.2 ± 6.4 years; N:12) and old-age (age 65.0 ± 7.7 years; N:12) for comparison with middle-aged non-athlete controls. Results: Healthy and morbidity MA groups showed similar BP responses during forearm occlusion and AGP (90.1 ± 4.3% and 91.0 ± 5.3%, p > 0.05, respectively). Healthy and morbidity MA showed modest correlation between the BP rising slope for 40%MVC ischaemic exercise and AGP (r = 0.5, p < 0.05). MA showed accelerated SBP recovery after cessation of ischaemic handgrip exercise compared to healthy non-athlete controls. Conclusion: Our findings associate long-term athletic training with improved BP recovery following ischaemic exercise regardless of age or reported morbidity. Exaggerated BP in Master cyclists during ischaemic exercise was associated with lower AGP during the World Master Cycling Championships

Fibromyalgia and Chronic Fatigue Syndromes: A systematic review and meta-analysis of cardiorespiratory fitness and neuromuscular function compared with healthy individuals

Objective: To determine cardiorespiratory fitness and neuromuscular function of people with CFS and FMS compared to healthy individuals. Design: Systematic review and meta-analysis. Data sources: PubMed, Medline, CINAHL, AMED, Cochrane Central Register of Controlled Trials (CENTRAL), and PEDro from inception to June 2022. Eligible criteria for selecting studies: Studies were included if presenting baseline data on cardiorespiratory fitness and/or neuromuscular function from observational or interventional studies of patients diagnosed with FMS or CFS. Participants were aged 18 years or older, with results also provided for healthy controls. Risk of bias assessment was conducted using the Quality Assessment Tool for Quantitative Studies (EPHPP). Results: 99 studies including 9853 participants (5808 patients; 4405 healthy controls) met our eligibility criteria. Random effects meta-analysis showed lower cardiorespiratory fitness (VO2max, anaerobic threshold, peak lactate) and neuromuscular function (MVC, fatigability, voluntary activation, muscle volume, muscle mass, rate of perceived exertion) in CFS and FMS compared to controls: all with moderate to high effect sizes. Discussion: Our results demonstrate lower cardiorespiratory fitness and muscle function in those living with FMS or CFS when compared to controls. There were indications of dysregulated neuro-muscular interactions including heightened perceptions of effort, reduced ability to activate the available musculature during exercise and reduced tolerance of exercise. Trail registration: PROSPERO registration number: (CRD42020184108)

The corticomuscular response to experimental pain via blood flow occlusion when applied to the ipsilateral and contralateral leg during an isometric force task

Blood flow occlusion (BFO) has been previously used to investigate physiological responses to muscle ischemia, showing increased perceptual effort (RPE) and pain along with impaired neuromuscular performance. However, at present, it is unclear how BFO alters corticomuscular activities when either applied to the exercising or nonexercising musculature. The present study therefore set out to assess the corticomuscular response to these distinct BFO paradigms during an isometric contraction precision task. In a repeated measures design, fifteen participants (age = 27.00 ± 5.77) completed 15 isometric contractions across three experimental conditions; no occlusion (CNTRL), occlusion of the contralateral (i.e., nonexercising) limb (CON-OCC), and occlusion of the ipsilateral (i.e., exercising) limb (IPS-OCC). Measures of force, electroencephalographic (EEG), and electromyographic (EMG) were recorded during contractions. We observed that IPS-OCC broadly impaired force steadiness, elevated EMG of the vastus lateralis, and heightened RPE and pain. IPSI-OCC also significantly decreased corticomuscular coherence during the early phase of contraction and decreased EEG alpha activity across the sensorimotor and temporoparietal regions during the middle and late phases of contraction compared with CNTRL. By contrast, CON-OCC increased perceived levels of pain (but not RPE) and decreased EEG alpha activity across the prefrontal cortex during the middle and late phases of contraction, with no changes observed for EMG and force steadiness. Together, these findings highlight distinctive psychophysiological responses to experimental pain via BFO showing altered cortical activities (CON-OCC) and altered cortical, corticomuscular, and neuromuscular activities (IPS-OCC) when applied to the lower limbs during an isometric force precision task

Hodgkin's lymphoma masquerading as vertebral osteomyelitis in a man with diabetes: a case report

<p>Abstract</p> <p>Introduction</p> <p>Infection and malignancy often have common characteristics which render the differential diagnosis for a prolonged fever difficult. Imaging and tissue biopsy are crucial in making a correct diagnosis, though differentiating between chronic osteomyelitis and malignancy is not always straightforward as they possess many overlapping features.</p> <p>Case Presentation</p> <p>A 52-year-old Caucasian man was treated with antibiotics for his diabetic foot infection after a superficial culture showed <it>Staphylococcus aureus</it>. He had persistent fevers for several weeks and later developed acute onset of back pain which was treated with several courses of antibiotics. Radiographic and pathological findings were atypical, and a diagnosis of Hodgkin's lymphoma was made 12 weeks later.</p> <p>Conclusion</p> <p>Clinicians should maintain a suspicion for Hodgkin's lymphoma or other occult malignancy when features of presumed osteomyelitis are atypical. Chronic vertebral osteomyelitis in particular often lacks features common to acute infectious disease processes, and the chronic lymphocytic infiltrates seen on histopathology have very similar features to Hodgkin's lymphoma, highlighting a similar inflammatory microenvironment sustained by both processes.</p