Subcutaneous emphysema in a case of infective sinusitis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Subcutaneous emphysema with pneumomediastinum is a rare phenomenon with a high morbidity and may occur spontaneously.</p> <p>Case presentation</p> <p>A 30-year-old Caucasian man presented with sudden onset of a painful, swollen neck and was found, via clinical and radiological examination to have subcutaneous emphysema. A swallow study showed no oesophageal perforation. Computed tomography of his neck and thorax demonstrated pneumomediastinum but no other pathology. Management was conservative with intravenous antibiotics, fluids and no oral intake. He had a history of a productive cough and a flexible nasoendoscopy found purulent sinusitis which was treated with topical nasal washes. The patient was discharged after 72 hours and will be followed up by the otolaryngology-head and neck service.</p> <p>Conclusions</p> <p>Infective sinusitis is a rare cause of subcutaneous emphysema and pneumomediastinum. It may be managed conservatively provided there is early recognition and exclusion of more serious pathology, such as a ruptured trachea or oesophagus.</p

Chronic Muscle Weakness and Mitochondrial Dysfunction in the Absence of Sustained Atrophy in a Preclinical Sepsis Model

Chronic critical illness is a global clinical issue affecting millions of sepsis survivors annually. Survivors report chronic skeletal muscle weakness and development of new functional limitations that persist for years. To delineate mechanisms of sepsis-induced chronic weakness, we first surpassed a critical barrier by establishing a murine model of sepsis with ICU-like interventions that allows for the study of survivors. We show that sepsis survivors have profound weakness for at least 1 month, even after recovery of muscle mass. Abnormal mitochondrial ultrastructure, impaired respiration and electron transport chain activities, and persistent protein oxidative damage were evident in the muscle of survivors. Our data suggest that sustained mitochondrial dysfunction, rather than atrophy alone, underlies chronic sepsis-induced muscle weakness. This study emphasizes that conventional efforts that aim to recover muscle quantity will likely remain ineffective for regaining strength and improving quality of life after sepsis until deficiencies in muscle quality are addressed

IODP workshop: Core-Log Seismic Investigation at Sea – Integrating legacy data to address outstanding research questions in the Nankai Trough Seismogenic Zone Experiment

The first International Ocean Discovery Program (IODP) Core-Log-Seismic Integration at Sea (CLSI@Sea) workshop, held in January–February 2018, brought together an international, multidisciplinary team of 14 early-career scientists and a group of scientific mentors specialized in subduction zone processes at the Nankai Trough, one of the Earth's most active plate-subduction zones located off the southwestern coast of Japan. The goal of the workshop was to leverage existing core, log, and seismic data previously acquired during the IODP's Nankai Trough Seismogenic Zone Experiment (NanTroSEIZE), to address the role of the deformation front of the Nankai accretionary prism in tsunamigenic earthquakes and slow slip in the shallow portion of the subduction interface. The CLSI@Sea workshop was organized onboard the D/V Chikyu concurrently with IODP Expedition 380, allowing workshop participants to interact with expedition scientists installing a long-term borehole monitoring system (LTBMS) at a site where the workshop's research was focused. Sedimentary cores from across the deformation front were brought onboard Chikyu, where they were made available for new description, sampling, and analysis. Logging data, drilling parameters, and seismic data were also available for investigation by workshop participants, who were granted access to Chikyu laboratory facilities and software to perform analyses at sea.Multi-thematic presentations facilitated knowledge transfer between the participants across field areas, and highlighted the value of multi-disciplinary collaboration that integrates processes across different spatiotemporal scales. The workshop resulted in the synthesis of existing geophysical, geologic, and geochemical data spanning IODP Sites C0006, C0007, C0011 and C0012 in the NanTroSEIZE area, the identification of key outstanding research questions in the field of shallow subduction zone seismogenesis, and fostered collaborative and individual research plans integrating new data analysis techniques and multidisciplinary approaches.</p

Increased expression of phosphorylated forms of RNA-dependent protein kinase and eukaryotic initiation factor 2α may signal skeletal muscle atrophy in weight-losing cancer patients

Previous studies suggest that the activation (autophosphorylation) of dsRNA-dependent protein kinase (PKR) can stimulate protein degradation, and depress protein synthesis in skeletal muscle through phosphorylation of the translation initiation factor 2 (eIF2) on the α-subunit. To understand whether these mediators are important in muscle wasting in cancer patients, levels of the phospho forms of PKR and eIF2α have been determined in rectus abdominus muscle of weight losing patients with oesophago-gastric cancer, in comparison with healthy controls. Levels of both phospho PKR and phospho eIF2α were significantly enhanced in muscle of cancer patients with weight loss irrespective of the amount and there was a linear relationship between phosphorylation of PKR and phosphorylation of eIF2α (correlation coefficient 0.76, P=0.005). This suggests that phosphorylation of PKR led to phosphorylation of eIF2α. Myosin levels decreased as the weight loss increased, and there was a linear relationship between myosin expression and the extent of phosphorylation of eIF2α (correlation coefficient 0.77, P=0.004). These results suggest that phosphorylation of PKR may be an important initiator of muscle wasting in cancer patients

Peak bone mineral density in Vietnamese women

While the prevalence of osteoporosis and risk factors for low bone mineral density (BMD) has been well documented in Caucasian populations, there is a lack of data from Asia. This work was designed to clarify to what extent osteoporosis could be regarded as a major public health problem in Vietnam. Furthermore, to elucidate the prevalence of certain risk factors, such as vitamin D deficiency and other determinants of bone mass as a basis to indentify high-risk individuals among the Vietnamese women and men. The clinical studies were designed as cross-sectional investigations using a multistage sampling scheme. Within the setting of northern Vietnam (latitude 21°N), districts were selected to represent urban and rural areas. In total 612 healthy women and 222 men aged 13-83 years were investigated. BMD was measured at the lumbar spine, femoral neck and total hip in all qualified subjects with dual energy X-ray absortiometry. Serum concentrations of 25(OH)D, parathyroid hormone, estrogen and testosterone were quantified by electrochemiluminescence immunoassay. Data on clinical history and lifestyle were collected by individual face-to-face interviews. Reference values for peak BMD were defined. These data allowed the calculation of T-scores and thus for the first time, an accurate identification of osteoporosis in a Vietnamese population. As determined at the femoral neck, the prevalence of osteoporosis was 17-23% in women and 9% in men. The results clearly suggest that osteoporosis is an important public health problem. Postmenopausal women living in urban areas experienced osteoporosis more than rural residents. Serum levels of 25(OH)D and estrogen were significantly associated with bone mass in both women and men. The prevalence of vitamin D deficiency (<20 ng/mL) was very high, 30% in women and 16% in men. An experimental study on the isoflavone content of different soymilk preparations was performed by HPLC (high pressure liquid chromatography). Values of isoflavones were very low, around 60-80 mg/L, and there were only 10-20% of bioactive aglycones. This is far below the reported threshold levels to exert significant effects on bone. In the future these data will be useful as a valuable reference base to diagnose osteoporosis and for the clinical management of its consequences. The high prevalence of vitamin D deficiency should raise the awareness of potentially important health issues such as osteoporosis but also about other serious diseases within the Vietnamese society

Natriuretic peptide activation of extracellular regulated kinase 1/2 (ERK1/2) pathway by particulate guanylyl cyclases in GH3 somatolactotropes.

The natriuretic peptides, Atrial-, B-type and C-type natriuretric peptides (ANP, BNP, CNP), are regulators of many endocrine tissues and exert their effects predominantly through the activation of their specific guanylyl cyclase receptors (GC-A and GC-B) to generate cGMP. Whereas cGMP-independent signalling has been reported in response to natriuretic peptides, this is mediated via either the clearance receptor (Npr-C) or a renal-specific NPR-Bi isoform, which both lack intrinsic guanylyl cyclase activity. Here, we report evidence of GC-B-dependent cGMP-independent signalling in pituitary GH3 cells. Stimulation of GH3 cells with CNP resulted in a rapid and sustained enhancement of ERK1/2 phosphorylation (P-ERK1/2), an effect that was not mimicked by dibutryl-cGMP. Furthermore, CNP-stimulated P-ERK1/2 occurred at concentrations below that required for cGMP accumulation. The effect of CNP on P-ERK1/2 was sensitive to pharmacological blockade of MEK (U0126) and Src kinases (PP2). Silencing of the GC-B1 and GC-B2 splice variants of the GC-B receptor by using targeted short interfering RNAs completely blocked the CNP effects on P-ERK1/2. CNP failed to alter GH3 cell proliferation or cell cycle distribution but caused a concentration-dependent increase in the activity of the human glycoprotein α-subunit promoter (αGSU) in a MEK-dependent manner. Finally, CNP also activated the p38 and JNK MAPK pathways in GH3 cells. These findings reveal an additional mechanism of GC-B signalling and suggest additional biological roles for CNP in its target tissues

A genome-wide association study of northwestern Europeans involves the C-type natriuretic peptide signaling pathway in the etiology of human height variation

Northwestern Europeans are among the tallest of human populations. The increase in body height in these people appears to have reached a plateau, suggesting the ubiquitous presence of an optimal environment in which genetic factors may have exerted a particularly strong influence on human growth. Therefore, we performed a genome-wide association study (GWAS) of body height using 2.2 million markers in 10 074 individuals from three Dutch and one German population-based cohorts. Upon genotyping, the 12 most significantly height-associated single nucleotide polymorphisms (SNPs) from this GWAS in 6912 additional individuals of Dutch and Swedish origin, a genetic variant (rs6717918) on chromosome 2q37.1 was found to be associated with height at a genome-wide significance level (Pcombined= 3.4 × 10-9). Notably, a second SNP (rs6718438) located ∼450 bp away and in strong LD (r2= 0.77) with rs6717918 was previously found to be suggestive of a height association in 29 820 individuals of mainly northwestern European ancestry, and the over-expression of a nearby natriuretic peptide precursor type C (NPPC) gene, has been associated with overgrowth and skeletal anomalies. We also found a SNP (rs10472828) located on 5p14 near the natriuretic peptide receptor 3 (NPR3) gene, encoding a receptor of the NPPC ligand, to be associated with body height (Pcombined= 2.1 × 10-7). Taken together, these results suggest that variation in the C-type natriuretic peptide signaling pathway, involving the NPPC and NPR3 genes, plays an important role in determining human body height

Primary Role of Functional Ischemia, Quantitative Evidence for the Two-Hit Mechanism, and Phosphodiesterase-5 Inhibitor Therapy in Mouse Muscular Dystrophy

Background. Duchenne Muscular Dystrophy (DMD) is characterized by increased muscle damage and an abnormal blood flow after muscle contraction: the state of functional ischemia. Until now, however, the cause-effect relationship between the pathogenesis of DMD and functional ischemia was unclear. We examined (i) whether functional ischemia is necessary to cause contraction-induced myofiber damage and (ii) whether functional ischemia alone is sufficient to induce the damage. Methodology/Principal Findings. In vivo microscopy was used to document assays developed to measure intramuscular red blood cell flux, to quantify the amount of vasodilatory molecules produced from myofibers, and to determine the extent of myofiber damage. Reversal of functional ischemia via pharmacological manipulation prevented contraction-induced myofiber damage in mdx mice, the murine equivalent of DMD. This result indicates that functional ischemia is required for, and thus an essential cause of, muscle damage in mdx mice. Next, to determine whether functional ischemia alone is enough to explain the disease, the extent of ischemia and the amount of myofiber damage were compared both in control and mdx mice. In control mice, functional ischemia alone was found insufficient to cause a similar degree of myofiber damage observed in mdx mice. Additional mechanisms are likely contributing to cause more severe myofiber damage in mdx mice, suggestive of the existence of a ‘‘two-hit’ ’ mechanism in the pathogenesis of this disease. Conclusions/Significance. Evidence was provided supporting the essential role of functional ischemia in contraction-induced myofiber damage in mdx mice. Furthermore, the first quantitative evidence for the ‘‘two-hit’ ’ mechanism in this disease was documented. Significantly, the vasoactive dru