We performed a pre/post-interventional study with participants as self-controls to evaluate the effects of consuming an evening-only low-carbohydrate meal (LCM) at 1800 h on biochemical measures of ...glucose and lipid metabolism. Study participants comprised 14 healthy men (age range, 20-29 y) who, consumed standard test meals (STMs) or LCM at 1800 h. Blood samples were collected at fasting, and at 60-, 120-, and 240 min after the start of the meals. The 60-min postprandial levels and the area under the curve (AUC) 0-120 min for plasma glucose were significantly lower after the LCM than after the STMs. The 60- and 120-min postprandial levels and the AUC 0-240 min for plasma insulin were significantly lower after the LCM than after the STMs (p<0.01). Postprandial triglyceride (TG) levels at 120- and 240 min and the AUC 0-240 min were significantly higher after the LCM than after the STMs (p<0.05, p<0.01, and p<0.05, respectively). The interleukin-6 levels were significantly higher 240 min after the STMs than before the meals (p<0.05), but not after the LCM. In these healthy volunteers, consuming an LCM at 1800 h suppressed postprandial hyperglycemia and insulin secretion; however, postprandial TG increased. Consuming an LCM at 1800 h was beneficial as it inhibited elevation of blood glucose; however, it may also increase the risk of arteriosclerosis through increasing TG levels.
There are several clinical diagnostic criteria for allergic bronchopulmonary aspergillosis (ABPA). However, these criteria have not been validated in detail, and no criteria for allergic ...bronchopulmonary mycosis (ABPM) are currently available.
This study proposes new diagnostic criteria for ABPA/ABPM, consisting of 10 components, and compares its sensitivity and specificity to existing methods.
Rosenberg-Patterson criteria proposed in 1977, the International Society for Human and Animal Mycology (ISHAM) criteria proposed in 2013, and this new criteria were applied to 79 cases with pathological ABPM and the control population with allergic mucin in the absence of fungal hyphae (n = 37), chronic eosinophilic pneumonia (n = 64), Aspergillus-sensitized severe asthma (n = 26), or chronic pulmonary aspergillosis (n = 24). These criteria were also applied to the 179 cases with physician-diagnosed ABPA/ABPM in a nationwide Japanese survey.
The sensitivity for pathological ABPM with Rosenberg-Patterson criteria, ISHAM criteria, and this new criteria were 25.3%, 77.2%, and 96.2%, respectively. The sensitivity for physician-diagnosed ABPA/ABPM were 49.2%, 82.7%, and 94.4%, respectively. The areas under the curve for the receiver-operating characteristic curves were 0.85, 0.90, and 0.98, respectively. The sensitivity for ABPM cases that were culture-positive for non-Aspergillus fungi were 13.0%, 47.8%, and 91.3%, respectively.
The new diagnostic criteria, compared with existing criteria, showed better sensitivity and specificity for diagnosing ABPA/ABPM.
The translocase of the outer mitochondrial membrane (TOM) is the main entry gate for proteins
. Here we use cryo-electron microscopy to report the structure of the yeast TOM core complex
at 3.8-Å ...resolution. The structure reveals the high-resolution architecture of the translocator consisting of two Tom40 β-barrel channels and α-helical transmembrane subunits, providing insight into critical features that are conserved in all eukaryotes
. Each Tom40 β-barrel is surrounded by small TOM subunits, and tethered by two Tom22 subunits and one phospholipid. The N-terminal extension of Tom40 forms a helix inside the channel; mutational analysis reveals its dual role in early and late steps in the biogenesis of intermembrane-space proteins in cooperation with Tom5. Each Tom40 channel possesses two precursor exit sites. Tom22, Tom40 and Tom7 guide presequence-containing preproteins to the exit in the middle of the dimer, whereas Tom5 and the Tom40 N extension guide preproteins lacking a presequence to the exit at the periphery of the dimer.
Chronic pulmonary aspergillosis (CPA) develops in various underlying pulmonary conditions. There is scarce data evaluating interstitial lung disease (ILD)/abnormalities (ILA) as such conditions, and ...it has not been explored much whether non-tuberculous mycobacterial pulmonary disease (NTM-PD) is a prognostic factor for mortality in CPA patients. Few reports had investigated prognostic factors of CPA including underlying pulmonary conditions.
To explore prognostic factors of CPA including pulmonary conditions.
We conducted a retrospective cohort study of 264 CPA patients from a center for pulmonary aspergillosis in Japan.
Survival rates were 78.7%, 61.0%, and 47.4% at 1, 3, and 5 years, respectively. Of 264 patients, 53 (20.1%) and 87 (33.1%) were complicated with ILA and NTM-PD. Several independent prognostic factors were identified by multivariate Cox proportional analysis: ILA (HR 1.76, 95%CI 1.06-2.92, p = 0.029), age (1.05, 1.02-1.08, p<0.001), male sex (2.48, 1.34-4.59, p = 0.004), body mass index of <18.5 kg/m2 (1,87, 1.20-2.90, p = 0.005), presence of aspergilloma (1.59, 1.04-2.45, p = 0.033), and lower serum albumin (0.56, 0.38-0.83, p = 0.004). NTM-PD was not associated with higher mortality (0.85, 0.52-1.38, p = 0.51).
The poor prognosis of CPA and several prognostic factors were revealed. Early diagnosis and intervention is required with reference to such factors.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective The incidence of tuberculosis in Japan has been decreasing in the overall population but is increasing in older patients ≥90 years old. A poor performance status due to underlying diseases ...makes it difficult for patients with tuberculosis to receive standard oral treatment. However, there is no consensus concerning alternative treatments. This study examined the treatments and outcomes of older patients with tuberculosis and a poor performance status and determined the limitations of tuberculosis treatment for them. Methods We retrospectively enrolled 121 older patients with tuberculosis and a performance status of 3 or 4 due to underlying diseases during their hospitalization between April 2015 and March 2017 at National Hospital Organization Tokyo National Hospital. We classified them according to the drug administration route (oral, enteral, and injection routes) on admission and compared the characteristics and prognoses among the three groups. Results There were 79 patients in the oral route group, 28 (35.4%) of whom died during hospitalization. Among the 15 patients in the enteral route group, 6 (40.0%) died. Among the 27 patients in the injection route group who received non-oral agents, 22 (81.5%) died. The prognosis of the injection route group was poor, with a median survival time of 21 days. Conclusion Treatment success cannot be expected with injection treatment in patients with a poor general condition because of complications. Although injection treatment may be a viable alternative treatment, its establishment as the standard treatment cannot be currently endorsed.
Exposure to environmental neurotoxic chemicals both in utero and during the early postnatal period can cause neurodevelopmental disorders. To evaluate the disruption of neurodevelopmental ...programming, we previously established an in vitro neurosphere assay system using rat mesencephalic neural stem cells that can be used to evaluate. Here, we extended the assay system to examine the neurodevelopmental toxicity of the endocrine disruptors butyl benzyl phthalate, di-n-butyl phthalate, dicyclohexyl phthalate, diethyl phthalate, di(2-ethyl hexyl) phthalate, di-n-pentyl phthalate, and dihexyl phthalate at a range of concentrations (0-100 μM). All phthalates tested inhibited cell migration with a linear or non-linear range of concentrations when comparing migration distance to the logarithm of the phthalate concentrations. On the other hand, some, but not all, phthalates decreased the number of proliferating cells. Apoptotic cells were not observed upon phthalate exposure under any of the conditions tested, whereas the dopaminergic toxin rotenone induced significant apoptosis. Thus, we were able to classify phthalate toxicity based on cell migration and cell proliferation using the in vitro neurosphere assay.
Aspergillus species have been identified morphologically in most clinical laboratories without conducting antifungal susceptibility tests (ASTs). This review aimed to evaluate the importance of ...accurate identification and ASTs of Aspergillus spp. strains for adequate clinical management of Aspergillus infections. The Aspergillus spp. were identified by gene sequencing, and ASTs for itraconazole and voriconazole were conducted. In Aspergillus section Nigri, the rate of detection of cryptic species was high, and Aspergillus tubingensis with lower susceptibility to azoles was frequently identified. Azole-resistant Aspergillus fumigatus was detected at a high rate in patients with chronic pulmonary aspergillosis managed with long-term azole treatment. In conclusion, accurate identification of Aspergillus spp. and ASTs are needed to carry out appropriate treatment. Moreover, we hope that these microbiological tests will be widely used in clinical laboratories to improve clinical practice.
Isavuconazole is a convenient triazole antifungal agent with a broad antifungal spectrum. A randomized, open-label study (ClinicalTrials.gov, NCT03471988) was conducted to evaluate the efficacy and ...safety of isavuconazole in Japanese patients with deep-seated mycoses.
In Cohort A, patients with aspergillosis (chronic pulmonary aspergillosis and invasive aspergillosis) were randomized in a 2:1 ratio to isavuconazole or voriconazole, and in Cohort B, patients with cryptococcosis and mucormycosis were assigned to isavuconazole for up to 84 days of treatment. The overall outcome was evaluated according to the clinical, radiological, and mycological responses at Days 42 and 84 and at the end of treatment (EOT).
A total of 103 participants were enrolled and received the study drug. The overall response rate of patients with chronic pulmonary aspergillosis in the isavuconazole (52 patients) and voriconazole (27 patients) groups was 82.7% and 77.8% at EOT, respectively. The response rate in patients with cryptococcosis (10 patients, isavuconazole group only) was 90.0%. One of three participants with invasive aspergillosis and one of three participants with mucormycosis responded in the isavuconazole group. In the safety evaluation, the incidence of adverse events in participants with chronic pulmonary aspergillosis was similar in both groups. Adverse drug reactions were reported in 32 (61.5%) patients receiving isavuconazole and 23 (85.2%) patients receiving voriconazole.
Isavuconazole showed efficacy and safety in Japanese patients with chronic pulmonary aspergillosis and cryptococcosis, for which the drug is not currently indicated.
Temperature variations in the tropical tropopause layer (TTL) play an important role in dehydration in the upper troposphere and lower stratosphere. Equatorial Kelvin waves associated with the ...Madden‐Julian Oscillation (MJO) are known to induce remarkable temperature variations in the TTL. In this study, the influence of topography on temperature variations in the TTL is investigated by using radiosonde data, satellite data, reanalysis data, and numerically simulated data. When MJO convection passes over the radiosonde sites, temperature variations near mountainous regions are larger than those measured in regions of lower elevation. The difference in temperature amplitude reaches ~1–2 K. Large temperature variations over mountainous regions were also found in other data sets. Numerically simulated data from the Nonhydrostatic Icosahedral Atmospheric Model (NICAM) are also used to investigate the temperature variations in the TTL. The results show that the temperature variations associated with Kelvin waves become large over mountainous regions. A sensitivity test using the stretched version of NICAM gave two important results: (i) the height of mountains affects the magnitude of the temperature variations in the TTL, and (ii) the terrain‐following coordinate system used in the model produces the artificially high‐temperature variation in the TTL. When Kelvin waves pass over mountainous regions, topographic gravity waves are excited and superimposed on the Kelvin waves, thereby producing large temperature variations over these regions. The mountainous region of the Indonesian Maritime Continent is a favorable location for large temperature variations in the TTL.
Key Points
Mountainous regions are favorable locations for large temperature variations in the TTL
Superposition of gravity waves and Kelvin waves has the potential to produce the coldest region
Terrain‐following coordinate system may produce unrealistic temperature variations in the TTL
Abstract
Observations of temperature and wind velocity in the 30–40-km altitude layer have been sparse since elimination of the standard rocketsonde sounding network in the 1990s. In an effort to ...extend the vertical range of radiosonde observations into the upper stratosphere, experiments were conducted with a 3-kg balloon at Tsukuba, Japan, on 5 November 2019. Using this relatively inexpensive balloon technology, four radiosondes were launched, with two reaching above 40-km altitude. These profiles were compared with satellite and reanalysis data in the 30–40-km layer, which showed an overall good agreement and an ability of radiosondes to capture shorter vertical-scale variations. The ability to quantify gravity wave parameters from the data is described, with application to wave events detected near 38–40 km. This type of balloon will be deployed extensively in an upcoming intensive observation campaign over the Maritime Continent, which will contribute toward achieving standard radiosonde observations in the 30–40-km altitude range. This system extends the ability to provide information regarding gravity wave and planetary wave activity upward to ∼40 km.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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