Less-invasive Treatment for Group A Streptococcal Fasciitis with Rapid Antigen Detection Test and Collagen/Gelatin Sponge

Patients with severe group A Streptococcus (GAS) induced necrotizing soft tissue infection sometimes develop Streptococcal toxic shock syndrome, which is a life-threatening condition with an extremely high fatality rate. Obtaining survival is the most important goal; however, an early diagnosis for debridement surgery and quick granulation formation for skin grafting surgery can better preserve the extremity functions. The patient was a 47-year-old man with a history of atopic dermatitis who presented with GAS-induced necrotizing soft tissue infection in his left lower extremity. His vital signs indicated shock, and he was diagnosed with streptococcal toxic shock syndrome. Emergency surgery was performed with his body pressure maintained with noradrenaline. Intraoperatively, rapid antigen detection tests (RADTs) were negative in the medial thigh and positive in the lower leg, which helped in decision-making regarding the area of aggressive debridement surgery. The wound culture results matched the intraoperative rapid antigen detection test results. A collagen/gelatin sponge with the sustained release of basic fibroblast growth factor was used as an artificial dermis before skin grafting. Excellent granulation was obtained, and skin grafting surgery was performed on the 11th day after collagen/gelatin sponge placement. He was discharged home on the 42nd day with normal lower extremity functions. First, an intraoperative diagnosis using GAS-rapid antigen detection tests with an appropriate sampling method from small incisions avoided excessive surgical debridement. Second, collagen/gelatin sponge with the sustained release of basic fibroblast growth factor promoted quick granulation tissue formation for wound bed preparation. These efforts resulted in the successful less-invasive treatment of a patient with streptococcal toxic shock syndrome caused by GAS-induced necrotizing soft tissue infection

Circulatory C-type natriuretic peptide reduces mucopolysaccharidosis-associated craniofacial hypoplasia in vivo

Skeletal alterations in the head and neck region, such as midfacial hypoplasia, foramen magnum stenosis and spinal canal stenosis, are commonly observed in patients with mucopolysaccharidosis (MPS). However, enzyme replacement therapy (ERT), one of the major treatment approaches for MPS, shows limited efficacy for skeletal conditions. In this study, we analysed the craniofacial morphology of mice with MPS type VII, and investigated the underlying mechanisms promoting jaw deformities in these animals. Furthermore, we investigated the effects of C-type natriuretic peptide (CNP), a potent endochondral ossification promoter, on growth impairment of the craniofacial region in MPS VII mice when administered alone or in combination with ERT. MPS VII mice exhibited midfacial hypoplasia caused by impaired endochondral ossification, and histological analysis revealed increased number of swelling cells in the resting zone of the spheno-occipital synchondrosis (SOS), an important growth centre for craniomaxillofacial skeletogenesis. We crossed MPS VII mice with transgenic mice in which CNP was expressed in the liver under the control of the human serum amyloid-P component promoter, resulting in elevated levels of circulatory CNP. The maxillofacial morphological abnormalities associated with MPS VII were ameliorated by CNP expression, and further prevented by a combination of CNP and ERT. Histological analysis showed that ERT decreased the swelling cell number, and CNP treatment increased the width of the proliferative and hypertrophic zones of the SOS. Furthermore, the foramen magnum and spinal stenoses observed in MPS VII mice were significantly alleviated by CNP and ERT combination. These results demonstrate the therapeutic potential of CNP, which can be used to enhance ERT outcome for MPS VII-associated head and neck abnormalities

Association Between Tooth Loss and Longitudinal Changes in B-Type Natriuretic Peptide Over 5 Years in Postmenopausal Women: The Nagahama Study

BACKGROUND: There is disparity between the sexes in cardiovascular diseases including heart failure (HF). This study aimed to investigate the effect of periodontal disease (PD) on plasma B-type natriuretic peptide (BNP) concentration across sex, age, and menopausal status, as well as the interaction effect of MT and diabetes mellitus (DM) on BNP. METHODS: This large-scale prospective cohort study enrolled 7, 539 individuals with no myocardial infarctions or angina pectoris at baseline from the general Japanese population. The association between baseline number of missing teeth (MT) and the longitudinal changes in BNP over 5 years (ΔBNP) was evaluated according to sex and menopausal status. RESULTS: Among 7, 539 participants, 3, 190 were postmenopausal women with a mean age ± standard deviation of 61.1 ± 7.6 at baseline. Multivariate analysis revealed a positive association between MT and ΔBNP among postmenopausal women even after adjusting for covariates, including traditional HF risk factors (coefficient, 0.210; 95% confidence interval [CI], 0.107 to 0.312; P 50. Including an interaction term (MT × DM) in the multivariate model revealed a positive interaction between MT and DM in ΔBNP among postmenopausal women (coefficient for interaction, 1.365; 95% CI, 0.902 to 1.827; P for interaction <0.001). CONCLUSIONS: Our study showed a positive association between MT and ΔBNP, as well as a positive effect of the interactive association between MT and DM, among postmenopausal women. Our results suggest a sex difference of an adverse effect of PD on initial myocardial wall stress in the ventricles

Optical transmittance investigation of 1-keV ion-irradiated sapphire crystals as potential VUV to NIR window materials of fusion reactors

We investigate the optical transmittances of ion-irradiated sapphire crystals as potential vacuum ultraviolet (VUV) to near-infrared (NIR) window materials of fusion reactors. Under potential conditions in fusion reactors, sapphire crystals are irradiated with hydrogen (H), deuterium (D), and helium (He) ions with 1-keV energy and ∼ 1020-m-2 s-1 flux. Ion irradiation decreases the transmittances from 140 to 260 nm but hardly affects the transmittances from 300 to 1500 nm. H-ion and D-ion irradiation causes optical absorptions near 210 and 260 nm associated with an F-center and an F+-center, respectively. These F-type centers are classified as Schottky defects that can be removed through annealing above 1000 K. In contrast, He-ion irradiation does not cause optical absorptions above 200 nm because He-ions cannot be incorporated in the crystal lattice due to the large ionic radius of He-ions. Moreover, the significant decrease in transmittance of the ion-irradiated sapphire crystals from 140 to 180 nm is related to the light scattering on the crystal surface. Similar to diamond polishing, ion irradiation modifies the crystal surface thereby affecting the optical properties especially at shorter wavelengths. Although the transmittances in the VUV wavelengths decrease after ion irradiation, the transmittances can be improved through annealing above 1000 K. With an optical transmittance in the VUV region that can recover through simple annealing and with a high transparency from the ultraviolet (UV) to the NIR region, sapphire crystals can therefore be used as good optical windows inside modern fusion power reactors in terms of light particle loadings of hydrogen isotopes and helium.Iwano K., Yamanoi K., Iwasa Y., et al. Optical transmittance investigation of 1-keV ion-irradiated sapphire crystals as potential VUV to NIR window materials of fusion reactors. AIP Advances 6, 105108 (2016); https://doi.org/10.1063/1.4965927

Metformin efficacy and safety for colorectal polyps: a double-blind randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Colorectal cancer is one of the major neoplasms and a leading cause of cancer death worldwide, and new preventive strategies are needed to lower the burden of this disease. Metformin, a biguanide, which is widely used for treating diabetes mellitus, has recently been suggestive to have a suppressive effect on tumorigenesis and cancer cell growth. In a previous study conducted in non-diabetic subjects, we showed that oral short-term low-dose metformin suppressed the development of colorectal aberrant crypt foci (ACF). ACF have been considered as a useful surrogate biomarker of CRC, although the biological significance of these lesions remains controversial. We devised a prospective randomized controlled trial to evaluate the chemopreventive effect of metformin against metachronous colorectal polyps and the safety of this drug in non-diabetic post-polypectomy patients.</p> <p>Methods/Design</p> <p>This study is a multi-center, double-blind, placebo-controlled, randomized controlled trial to be conducted in non-diabetic patients with a recent history of undergoing colorectal polypectomy. All adult patients visiting the Yokohama City University hospital or affiliated hospitals for polypectomy shall be recruited for the study. Eligible patients will then be allocated randomly into either one of two groups: the metformin group and the placebo group. Patients in the metformin group shall receive oral metformin at 250 mg per day, and those in the placebo group shall receive an oral placebo tablet. At the end of 1 year of administration of metformin/placebo, colonoscopy will be performed to evaluate the polyp formation.</p> <p>Discussion</p> <p>This is the first study proposed to explore the effect of metformin against colorectal polyp formation. Metformin activates AMPK, which inhibits the mammalian target of rapamycin (mTOR) pathway. The mTOR pathway plays an important role in the cellular protein translational machinery and cell proliferation. Patients with type 2 diabetes taking under treatment with metformin have been reported to be at a lower risk of cancer development than those not taking under treatment with metformin. We showed in a previous study that metformin suppressed the formation of human colorectal ACF. We therefore decided to conduct a study to determine whether metformin might suppress the formation of human colorectal polyps.</p> <p>Trial registration</p> <p>This trial has been registered in the University hospital Medical Information Network (UMIN) Clinical Trials Registry as <a href="http://www.clinicaltrials.gov/ct2/show/UMIN000006254">UMIN000006254</a></p

The Src/c-Abl pathway is a potential therapeutic target in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS), a fatal disease causing progressive loss of motor neurons, still has no effective treatment. We developed a phenotypic screen to repurpose existing drugs using ALS motor neuron survival as readout. Motor neurons were generated from induced pluripotent stem cells (iPSCs) derived from an ALS patient with a mutation in superoxide dismutase 1 (SOD1). Results of the screen showed that more than half of the hits targeted the Src/c-Abl signaling pathway. Src/c-Abl inhibitors increased survival of ALS iPSC-derived motor neurons in vitro. Knockdown of Src or c-Abl with small interfering RNAs (siRNAs) also rescued ALS motor neuron degeneration. One of the hits, bosutinib, boosted autophagy, reduced the amount of misfolded mutant SOD1 protein, and attenuated altered expression of mitochondrial genes. Bosutinib also increased survival in vitro of ALS iPSC-derived motor neurons from patients with sporadic ALS or other forms of familial ALS caused by mutations in TAR DNA binding protein (TDP-43) or repeat expansions in C9orf72. Furthermore, bosutinib treatment modestly extended survival of a mouse model of ALS with an SOD1 mutation, suggesting that Src/c-Abl may be a potentially useful target for developing new drugs to treat ALS

Effect of arterial carbon dioxide on ventilation during recovery from impulse exercises of various intensities

To determine that whether arterial carbon dioxide (PaCO2) affects ventilation (VE) during recovery from impulse-like exercises of various intensities, subjects performed four impulse-like tests with different workloads. Each test consisted of a 20-sec impulse-like exercise at 80 rpm and 60-min recovery. Blood samples were collected at rest and during recovery to measure blood ions and gases. VE was measured continuously during rest, exercise and recovery periods. A significant curvilinear relationship was observed between VE and pH during recovery from the 300 and 400 watts tests in all subjects. VE was elevated during recovery from the 100 watts test despite no change in any of the humoral factors. Arterialized carbon dioxide (PaCO2) kinetics showed fluctuation, being increased at 1 min and decreased at 5 min during recovery, and this fluctuation was more enhanced with increase in exercise intensity. There was a significant relationship between VE and PaCO2 during recovery from the 300 and 400 watts tests in all subjects. The results of the present study demonstrate that pH and neural factors drive VE during recovery from impulse-like exercise and that fluctuation in PaCO2 controls VE as a feedback loop and this feedback function is more enhanced as the work intensity increases