Effects of weight loss on metabolic dysfunction-associated fatty liver disease in Japanese people: Non-alcoholic fatty liver disease in the Gifu area, longitudinal analysis study.

AIM: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a major health concern. This cohort study aimed to evaluate the association between weight loss and remission of MAFLD in the Japanese population to aid the development of efficient treatment strategies. METHODS: This retrospective cohort study was conducted at a Japanese health screening center. Participants included 3309 individuals diagnosed with baseline MAFLD between 2004 and 2016. Logistic regression analysis was used to assess the association between MAFLD remission from baseline to 5 years and weight change. RESULTS: After 5 years, 671 participants achieved MAFLD remission. Weight loss was associated with MAFLD remission for every 1 kg of weight loss over 5 years; the odds ratio for MAFLD remission was 1.24 (95% CI 1.15-1.34) for participants with type 2 diabetes, 1.40 (95% CI 1.35-1.45) for overweight participants, and 1.51 (95% CI 1.33-1.72) for non-overweight participants with metabolic dysfunctions. The cutoff values for weight loss for MAFLD remission were 1.9 kg for all participants, 3.0 kg for participants with type 2 diabetes, 1.9 kg for overweight participants, and 0.8 kg for non-overweight participants with metabolic dysfunctions. CONCLUSIONS: Among participants diagnosed with MAFLD, weight loss was associated with MAFLD remission regardless of the type of metabolic dysfunction in MAFLD. The results of this study may contribute to the development of novel approaches to achieve MAFLD remission.

Discovery of a big void in Khufu's Pyramid by observation of cosmic-ray muons.

The Great Pyramid, or Khufu's Pyramid, was built on the Giza plateau in Egypt during the fourth dynasty by the pharaoh Khufu (Cheops), who reigned from 2509 bc to 2483 bc. Despite being one of the oldest and largest monuments on Earth, there is no consensus about how it was built. To understand its internal structure better, we imaged the pyramid using muons, which are by-products of cosmic rays that are only partially absorbed by stone. The resulting cosmic-ray muon radiography allows us to visualize the known and any unknown voids in the pyramid in a non-invasive way. Here we report the discovery of a large void (with a cross-section similar to that of the Grand Gallery and a minimum length of 30 metres) situated above the Grand Gallery. This constitutes the first major inner structure found in the Great Pyramid since the nineteenth century. The void, named ScanPyramids' Big Void, was first observed with nuclear emulsion films installed in the Queen's chamber, then confirmed with scintillator hodoscopes set up in the same chamber and finally re-confirmed with gas detectors outside the pyramid. This large void has therefore been detected with high confidence by three different muon detection technologies and three independent analyses. These results constitute a breakthrough for the understanding of the internal structure of Khufu's Pyramid. Although there is currently no information about the intended purpose of this void, these findings show how modern particle physics can shed new light on the world's archaeological heritage.

Home-measured pulse pressure is a predictor of cardiovascular disease in type 2 diabetes: The KAMOGAWA-HBP study.

BACKGROUND AND AIMS: Pulse pressure (PP) is a prognostic predictor of cardiovascular mortality. This retrospective cohort study aimed to investigate the association between home PP measurements and cardiovascular disease in patients with type 2 diabetes. METHODS AND RESULTS: Home blood pressure was measured for 14 consecutive days in 1082 patients with type 2 diabetes, and pulse pressure was calculated. A 10 mmHg increase in morning PP was associated with a 1.30-fold increase in the risk of cardiovascular disease. The risk of cardiovascular disease was 1.88 times higher in the morning in the higher PP group than in the lower PP group. In the receiver operating characteristic analysis, the areas under the curve (95% confidence interval) corresponding to the PP (morning, evening, and clinic) for new-onset cardiovascular disease were 0.63 (0.58-0.69), 0.62 (0.57-0.67), and 0.59 (0.54-0.64), respectively. The area under the curve for PP measured in the morning was significantly greater than that for PP measured in the clinic (P = 0.032). CONCLUSION: Home-measured PP is a better predictor of new-onset cardiovascular disease than clinic-measured PP, in patients with type 2 diabetes.

Effects of dietary salt restriction on home blood pressure in diabetic patients with excessive salt intake: a pilot study.

The aim of the present study was to examine whether dietary salt restriction guidance is beneficial for dietary salt restriction and lowering of home blood pressure in patients with diabetes with excessive salt intake. We performed an intervention trial of 37 people with type 2 diabetes and excessive salt intake. National registered dietitians provided dietary salt restriction guidance to each patient at the start of the study. All participants were instructed to perform triplicate morning and evening home blood pressure measurements using home blood pressure telemonitoring system. Daily salt intake at 2 months and 6 months was significantly lower than that at baseline; the difference was 0.8 [95% confidence interval (CI): 0.2-1.4, p = 0.009] g and 0.7 (95% CI: 0.1-1.3, p = 0.009) g, respectively. Morning systolic blood pressure at 2 months and 6 months was significantly lower than that at baseline; the difference was 2.7 (95% CI: 0.2-5.1, p = 0.034) mmHg and 5.8 (95% CI: 0.5-11.1, p = 0.034) mmHg, respectively. This intervention study revealed, for the first time, that dietary salt restriction guidance provided by a national registered dietitian is beneficial for reducing daily salt intake and home blood pressure in people with diabetes with excessive salt intake.

Associations between thyroid hormones and appendicular skeletal muscle index, and hand grip strength in people with diabetes: The KAMOGAWA-A study.

AIM: To assess the effects of thyroid hormones on appendicular skeletal muscle index (SMI) and hand grip strength (HGS) in people with diabetes. METHODS: This cross-sectional cohort included 1,135 participants with diabetes admitted to 3 hospitals in Japan. Multiple regression analysis was performed to determine the associations among thyroid hormone levels, SMI, and HGS. RESULTS: Of the 1,135 participants, 480 were female. Their median (interquartile range) age, body mass index, durations of diabetes, and glycated haemoglobin levels were 68 years, 24.3 kg/m2, 10 years, and 7.6 %, respectively. The median (interquartile range) SMI (kg/m2) and hand grip strength of the cohort were 7.1 kg/m2 and 28.2 kg, respectively. Positive correlations between FT3 and the FT3/FT4 ratio with SMI and HGS was observed after adjusting for covariates in males. A negative correlation was found between the FT3/FT4 ratio and sarcopenia as a result of low SMI and low HGS in the male participants but not in females (p for interaction = 0.02). CONCLUSIONS: FT3/FT4 ratios may impact skeletal muscles in people with diabetes-particularly in males. Assessments of FT3/FT4 ratios may represent key indicators of muscle mass and strength in males.

Daidzein Inhibits Muscle Atrophy by Suppressing Inflammatory Cytokine- and Muscle Atrophy-Related Gene Expression.

BACKGROUND: Sarcopenic obesity, which is associated with a poorer prognosis than that of sarcopenia alone, may be positively affected by soy isoflavones, known inhibitors of muscle atrophy. Herein, we hypothesize that these compounds may prevent sarcopenic obesity by upregulating the gut metabolites with anti-inflammatory effects. METHODS: To explore the effects of soy isoflavones on sarcopenic obesity and its mechanisms, we employed both in vivo and in vitro experiments. Mice were fed a high-fat, high-sucrose diet with or without soy isoflavone supplementation. Additionally, the mouse C2C12 myotube cells were treated with palmitic acid and daidzein in vitro. RESULTS: The isoflavone considerably reduced muscle atrophy and the expression of the muscle atrophy genes in the treated group compared to the control group (Fbxo32, p = 0.0012; Trim63, p < 0.0001; Foxo1, p < 0.0001; Tnfa, p = 0.1343). Elevated levels of daidzein were found in the muscles and feces of the experimental group compared to the control group (feces, p = 0.0122; muscle, p = 0.0020). The real-time PCR results demonstrated that the daidzein decreased the expression of the palmitate-induced inflammation and muscle atrophy genes in the C2C12 myotube cells (Tnfa, p = 0.0201; Il6, p = 0.0008; Fbxo32, p < 0.0001; Hdac4, p = 0.0002; Trim63, p = 0.0114; Foxo1, p < 0.0001). Additionally, it reduced the palmitate-induced protein expression related to the muscle atrophy in the C2C12 myotube cells (Foxo1, p = 0.0078; MuRF1, p = 0.0119). CONCLUSIONS: The daidzein suppressed inflammatory cytokine- and muscle atrophy-related gene expression in the C2C12 myotubes, thereby inhibiting muscle atrophy.

Milk protects against sarcopenic obesity due to increase in the genus Akkermansia in faeces of db/db mice.

BACKGROUND: Sarcopenic obesity, a combination of sarcopenia and obesity, is a pathological feature of type 2 diabetes. Several human studies have shown that milk is useful in the prevention of sarcopenia. This study was aimed at clarifying the effect of milk on the prevention of sarcopenic obesity in db/db mice. METHODS: A randomized and investigator-blinded study was conducted using male db/db mice. Eight-week-old db/db mice were housed for 8 weeks and fed milk (100 µL/day) using a sonde. The faecal microbiota transplantation (FMT) group received antibiotics for 2 weeks, starting at 6 weeks of age, followed by FMT twice a week until 16 weeks of age. RESULTS: Milk administration to db/db mice increased grip strength (Milk-: 164.2 ± 4.7 g, Milk+: 230.2 ± 56.0 g, P = 0.017), muscle mass (soleus muscle, Milk-: 164.2 ± 4.7 mg, Milk+: 230.2 ± 56.0 mg, P < 0.001; plantaris muscle, Milk-: 13.3 ± 1.2 mg, Milk+: 16.0 ± 1.7 mg, P < 0.001) and decreased visceral fat mass (Milk-: 2.39 ± 0.08 g, Milk+: 1.98 ± 0.04 mg, P < 0.001), resulting in a significant increase in physical activity (light: P = 0.013, dark: P = 0.034). FMT from mice fed milk not only improved sarcopenic obesity but also significantly improved glucose intolerance. Microarray analysis of gene expression in the small intestine revealed that the expression of amino acid absorption transporter genes, namely, SIc7a5 (P = 0.010), SIc7a1 (P = 0.015), Ppp1r15a (P = 0.041) and SIc7a11 (P = 0.029), was elevated in mice fed milk. In 16S rRNA sequencing of gut microbiota, the genus Akkermansia was increased in both the mice fed milk and the FMT group from the mice fed milk. CONCLUSIONS: The findings of this study suggest that besides increasing the intake of nutrients, such as amino acids, milk consumption also changes the intestinal environment, which might contribute to the mechanism of milk-induced improvement of sarcopenic obesity.

Metabolic outcomes and changes in innate immunity induced by diesel exhaust particles airway exposure and high-fat high-sucrose diet.

AIMS: Epidemiological studies have shown that exposure to diesel exhaust particles (DEP) is associated with metabolic diseases. We used mice with nonalcoholic fatty liver disease (NAFLD) caused by a high-fat, high-sucrose diet (HFHSD), which mimics a Western diet, to investigate the mechanism of NAFLD exacerbation via changes in innate immunity in the lungs by airway exposure to DEP. MAIN METHODS: Six-week-old C57BL6/J male mice were fed HFHSD, and DEP was administered endotracheally once a week for eight weeks. The histology, gene expression, innate immunity cells in the lung and liver, and the serum inflammatory cytokine levels, were investigated. KEY FINDINGS: Under the HFHSD, DEP increased blood glucose levels, serum lipid levels, and NAFLD activity scores, and also the expression of genes associated with inflammation in the lungs and liver. DEP caused an increase in ILC1s, ILC2s, ILC3s, and M1 macrophages in the lungs and a marked increase in ILC1s, ILC3s, M1 macrophages, and natural killer cells in the liver, while ILC2 levels were not changed. Furthermore, DEP caused high levels of inflammatory cytokines in the serum. SIGNIFICANCE: Chronic exposure to DEP in HFHSD-fed mice increased inflammatory cells involved in innate immunity in the lungs and raised local inflammatory cytokine levels. This inflammation spread throughout the body, suggesting the association with the progression of NAFLD via increased inflammatory cells involved in innate immunity and inflammatory cytokine levels in the liver. These findings contribute to a better understanding of the role of innate immunity in air pollution-related systemic diseases, especially metabolic diseases.

Predictive power of isolated high home systolic blood pressure for cardiovascular outcomes in individuals with type 2 diabetes mellitus: KAMOGAWA-HBP study.

AIMS/INTRODUCTION: Isolated high home systolic blood pressure (IHHSBP) is a risk for cardiovascular disease (CVD). However, no study has shown an association between IHHSBP and CVD in diabetes. We examined the association between IHHSBP and CVD in type 2 diabetes. MATERIALS AND METHODS: This retrospective cohort study included 1082 individuals with type 2 diabetes, aged 20 to 90 years, without a history of macrovascular complications. Home blood pressure (HBP) was measured three times every morning and evening for 14 days. Cox proportional hazards models were used to examine the relationship between IHHSBP and CVD incidence. RESULTS: With the normal HBP group as the reference, the adjusted hazard ratio (HR) (95% confidence interval [CI]) for CVD was 1.58 (1.02-2.43) in the IHHSBP group. Correcting for antihypertensive medication use did not change HR. Based on sex, the adjusted HR (95% CI) for CVD was 1.25 (0.74-2.13) in males and 2.28 (1.01-5.15) in females. CONCLUSIONS: In individuals with type 2 diabetes, those with IHHSBP had a higher HR for cardiovascular disease than those with normal HBP. But, Isolated high home diastolic blood pressure and high HBP were not. The association between IHHSBP and CVD was stronger in females than in males.

Reasons for Discontinuing Treatment with Sodium-Glucose Cotransporter 2 Inhibitors in Patients with Diabetes in Real-World Settings: The KAMOGAWA-A Study.

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are a class of antidiabetic agents known to exert cardioprotective, renoprotective, and hypoglycemic effects. However, these agents have been associated with adverse effects, such as genital infection, volume depletion, hypoglycemia, and diabetic ketoacidosis, resulting in drug discontinuation. Herein, we aimed to determine the reasons for discontinuing treatment with SGLT2is among Japanese patients with diabetes. This retrospective cohort study enrolled 766 patients with diabetes who had initiated SGLT2is between January 2014 and September 2021. The follow-up period was 2 years from the initiation of the SGLT2is. Overall, 97 patients (12.7%) discontinued the SGLT2is during the follow-up period. The most common reasons for discontinuing the SGLT2is were frequent urination (19.6%), followed by genital infection (11.3%), improved glycemic control (10.6%), and renal dysfunction (8.2%). A comparison of the characteristics between the continuation and the discontinuation group was conducted, excluding those who discontinued the SGLT2is because of improved glycemic control. The patients in the discontinuation group (68 [55-75] years) were older than those in the continuation group (64 [53-71] years; p = 0.003). Importantly, we found no significant association between diabetes duration, diabetic control, renal function, or complications of diabetes in both groups. This real-world study revealed that frequent urination was the most common reason underlying SGLT2i discontinuation among Japanese patients with diabetes. To avoid discontinuation, precautions against various factors that may cause frequent urination must be implemented.

Hidden chamber discovery in the underground Hellenistic necropolis of Neapolis by muography.

We report in this paper the muography of an archaeological site located in the highly populated "Sanità" district in the center of Naples, ten meters below the current street level. Several detectors capable of detecting muons - high energy charged particles produced by cosmic rays in the upper layers of atmosphere - were installed underground at the depth of 18 m, to measure the muon flux over several weeks. By measuring the differential flux with our detectors in a wide angular range, we have produced a radiographic image of the upper layers. Despite the architectural complexity of the site, we have clearly observed the known structures as well as a few unknown ones. One of the observed new structures is compatible with the existence of a hidden, currently inaccessible, burial chamber.

Impact of continued high blood pressure on the progression of diabetic nephropathy after 10 years: KAMOGAWA-HBP study.

Albuminuria is a prognostic marker of worsening renal outcomes in people with hypertension and type 2 diabetes. High home systolic blood pressure is associated with the development of diabetic nephropathy. We assessed the impact of chronic high home blood pressure on diabetic nephropathy progression 10 years after study entry. The participants measured their blood pressure three times in the morning for 14 days at study entry and 10 years after study entry. A retrospective cohort of 165 people with type 2 diabetes at a single hospital was classified into four groups (good control maintenance, improvement, deterioration, and continuous high blood pressure groups) according to a morning home systolic blood pressure ≥125 mmHg at study entry and 10 years after study entry. Logistic regression analysis was performed to determine the association between home blood pressure control and the progression of diabetic nephropathy. After 10 years of entry, the status of nephropathy improved for 5.5% of the participants, remained unchanged for 72.1%, and progressed for 22.4%. The odds ratio of the continuous high blood pressure group versus that of the good control maintenance group for the progression of diabetic nephropathy was 10.41 (95% CI, 1.26-86.15). After adjusting for the introduction of renin-angiotensin-aldosterone system inhibitors during the follow-up period, there was no significant difference in the odds ratio of worsening nephropathy between these groups. The deterioration and improvement groups did not have significant diabetic nephropathy progression compared to the good control maintenance group. Chronic high home blood pressure was associated with the progression of diabetic nephropathy, and RAAS inhibitors could attenuate the negative effect. We demonstrated that chronic home blood pressure was associated with the progression of diabetic nephropathy.

Precise characterization of a corridor-shaped structure in Khufu's Pyramid by observation of cosmic-ray muons.

Khufu's Pyramid is one of the largest archaeological monument all over the world, which still holds many mysteries. In 2016 and 2017, the ScanPyramids team reported on several discoveries of previously unknown voids by cosmic-ray muon radiography that is a non-destructive technique ideal for the investigation of large-scale structures. Among these discoveries, a corridor-shaped structure has been observed behind the so-called Chevron zone on the North face, with a length of at least 5 meters. A dedicated study of this structure was thus necessary to better understand its function in relation with the enigmatic architectural role of this Chevron. Here we report on new measurements of excellent sensitivity obtained with nuclear emulsion films from Nagoya University and gaseous detectors from CEA, revealing a structure of about 9 m length with a transverse section of about 2.0 m by 2.0 m.

Diabetic nephropathy ameliorated in patients with normal home blood pressure compared to those with isolated high home systolic blood pressure: A 5-year prospective cohort study among patients with type 2 diabetes mellitus.

BACKGROUND: Using normal home blood pressure (home BP) as a reference, isolated high home systolic blood pressure (IH-home SBP) increases the risk of diabetic nephropathy. However, whether diabetic nephropathy would improve among diabetic patients without IH-home SBP has not been previously assessed. METHODS: This prospective 5-year cohort study of 264 patients with moderate or severe albuminuria investigated the effect of IH-home SBP or normal home BP on the risk of diabetic nephropathy in patients with type 2 diabetes mellitus. Improvement of diabetic nephropathy was defined as remission or regression from moderate or severe albuminuria to normal or mildly increased albuminuria. RESULTS: Improvement of diabetic nephropathy was shown in 59 out of 264 patients during 5 years. The adjusted odds ratio (95% confidence interval) of normal home BP for improving diabetic nephropathy was 2.52 (1.01-5.99, p = 0.05). CONCLUSION: Normal home BP had relation to an improvement in diabetic nephropathy among type 2 diabetic patients with moderate and severe increased albuminuria in the observation period of 5 years. Good home BP control might be valuable to ameliorate diabetic nephropathy.

Impact of untreated diabetes and COVID-19-related diabetes on severe COVID-19.

Diabetes is a common comorbidity in patients with coronavirus disease (COVID-19) and contributes significantly to COVID-19 severity. We aimed to investigate the association between diabetic status and severe COVID-19. This prospective study included all COVID-19 patients admitted to our hospital, who were divided into four groups according to their diabetic status: no diabetes, treated diabetes, untreated diabetes, and COVID-19-related diabetes. Severe COVID-19 was defined as a condition that required the use of a ventilator. Of the 114 patients included in this study, 26 had severe COVID-19. The adjusted odds ratio (OR; 95% confidence interval [CI]) for severe COVID-19 was significantly higher in the treated diabetes, untreated diabetes, and COVID-19-related diabetes groups than in the no diabetes group (OR: 5.9, 95% CI [1.2-27.9]; OR 12.6, 95% CI [1.8-86.4]; and OR: 9.3, 95% [1.1-81.4], respectively). Findings from this study showed that the risk of severe COVID-19 was increased in treated diabetes, untreated diabetes, and COVID-19-related diabetes compared to no diabetes. Furthermore, the OR for severe COVID-19 was greater in untreated diabetes and COVID-19-related diabetes than in treated diabetes.

Impact of sustained hypertension on new cardiovascular events in patients with type 2 diabetes: KAMOGAWA-HBP study.

We have previously shown that masked hypertension (MH) and sustained hypertension (SH) contribute to the progression of diabetic nephropathy. Although the risk of target organ damage and cardiovascular events in MH and SH is significantly higher than that in normotension and white coat hypertension, the role of MH or SH in cardiovascular events has never been reported in studies specific to diabetic patients. Therefore, in this study, we aimed to determine whether blood pressure control status contributes to the development of new cardiovascular events. A longitudinal study of 1082 patients with type 2 diabetes mellitus and no history of cardiovascular events was conducted. Patients were instructed to have their blood pressure measured three times, every morning and evening, for 14 consecutive days. Hypertension status was classified into four groups based on the systolic blood pressure measurements in the clinic and at home. The primary endpoint was the first cardiovascular event. After a median follow-up of 7.0 (interquartile range, 4.0-9.0) years, 119 patients developed cardiovascular events. The hazard ratio (95% confidence interval) for the risk of developing cardiovascular events was significantly higher in the SH group than in the controlled blood pressure group (1.63 [1.02-2.59]). SH is a useful predictor of cardiovascular events. Both at home and in the clinic, blood pressure monitoring should be assessed in routine clinical practice to predict future cardiovascular events in patients with type 2 diabetes.

Gut Microbiota Changes by an SGLT2 Inhibitor, Luseogliflozin, Alters Metabolites Compared with Those in a Low Carbohydrate Diet in db/db Mice.

In recent years, sarcopenic obesity has been considered central pathological factors in diabetes. This study aimed to compare the effect of luseogliflozin, a sodium-glucose co-transporter-2 inhibitor (SGLT2i), on sarcopenic obesity in comparison to that of a low-carbohydrate diet (LCD). Twenty-week-old male db/db mice were fed a normal diet (Ctrl), LCD, and normal diet with 0.01% w/w luseogliflozin (SGLT2i) for eight weeks. Skeletal muscle mass and grip strength decreased in the LCD group mice compared to those in the control group, while they increased in the SGLT2i group mice. The amino acid content in the liver, skeletal muscle, and serum were lower in the LCD group than those in the Ctrl group but increased in the SGLT2i group mice. Short-chain fatty acids in rectal feces were lower in the LCD group mice than those in the Ctrl group, whereas they were higher in the SGLT2i group mice. The abundance of Gammaproteobacteria, Enterobacteriaceae, Escherichia, Enterobacterales, and Bacteroides caccae species increased in the LCD group compared to the other two groups, whereas the abundance of Syntrophothermus lipocalidus, Syntrophomonadaceae family, Parabacteroidesdistasonis distasonis, and the genus Anaerotignum increased in the SGLT2i group. Luseogliflozin could prevent sarcopenic obesity by improving amino acid metabolism.

Maximum home blood pressure and cardiovascular outcomes in patients with type 2 diabetes: KAMOGAWA-HBP study.

OBJECTIVE: The maximum blood pressure was reported as a possible marker of organ damage. We previously showed that maximum home blood pressure was significantly associated with development of diabetic nephropathy. In the same cohort of patients with diabetes as in the previous study, this study aimed to evaluate the prognostic blood pressure values for the onset of first cardiovascular events. METHODS: This retrospective cohort study included 1082 patients with type 2 diabetes (47.0% female, median age 65.0) without a history of macrovascular complications. Blood pressure measurements were performed in triplicates every morning and evening for 14 consecutive days from the start of the study. Cox hazards model was used to evaluate the risk of primary endpoint, which was defined as the onset of first major cardiovascular event. RESULTS: The primary endpoint occurred in 119 patients (incidence rate, 15.7/1000 person-years) during an average of 7.0-year follow-up. The adjusted hazard ratios (95% confidence interval [CI]) of maximum morning systolic blood pressure (SBP) and maximum evening SBP for cardiovascular events were 1.12 (1.01-1.24) and 1.19 (1.07-1.31), respectively, adjusted by sex, duration of diabetes, body mass index, hemoglobin A1c, low density lipoprotein cholesterol, smoking status, and use of antihypertensive medications. The cutoff values of maximum blood pressure for the events were 150 mmHg in the morning (hazard ratio, 1.73; 95% CI, 1.07-2.81) and 157 mmHg in the evening (hazard ratio, 2.30; 95% CI, 1.46-3.61), using the Youden's index. CONCLUSION: Maximum home blood pressure is a predictor of subsequent cardiovascular events in patients with type 2 diabetes.

Laser-driven multi-MeV high-purity proton acceleration via anisotropic ambipolar expansion of micron-scale hydrogen clusters.

Multi-MeV high-purity proton acceleration by using a hydrogen cluster target irradiated with repetitive, relativistic intensity laser pulses has been demonstrated. Statistical analysis of hundreds of data sets highlights the existence of markedly high energy protons produced from the laser-irradiated clusters with micron-scale diameters. The spatial distribution of the accelerated protons is found to be anisotropic, where the higher energy protons are preferentially accelerated along the laser propagation direction due to the relativistic effect. These features are supported by three-dimensional (3D) particle-in-cell (PIC) simulations, which show that directional, higher energy protons are generated via the anisotropic ambipolar expansion of the micron-scale clusters. The number of protons accelerating along the laser propagation direction is found to be as high as 1.6 [Formula: see text] [Formula: see text] 10[Formula: see text]/MeV/sr/shot with an energy of 2.8 [Formula: see text] MeV, indicating that laser-driven proton acceleration using the micron-scale hydrogen clusters is promising as a compact, repetitive, multi-MeV high-purity proton source for various applications.

Impact of Isolated High Home Systolic Blood Pressure and Diabetic Nephropathy in Patients with Type 2 Diabetes Mellitus: A 5-Year Prospective Cohort Study.

BACKGROUND: A previous 2-year cohort study has shown that isolated high home systolic blood pressure (IH-HSBP) may increase the risk of diabetic nephropathy, using normal HBP as a reference. However, this association has not been previously assessed in the medium to long term. METHODS: This prospective 5-year cohort study of 424 patients, with normal or mildly increased albuminuria, investigated the effect of IH-HSBP on the risk of diabetic nephropathy in patients with type 2 diabetes mellitus. Diabetic nephropathy was defined as an advancement from normal or mildly increased albuminuira to moderate or severely increased albuminuria. RESULTS: Among 424 patients, 75 developed diabetic nephropathy during the study period. The adjusted odds ratio for developing diabetic nephropathy given IH-HSBP was 2.39 (95% confidence interval, 1.15-4.96, p = 0.02). The odds ratio for developing nephropathy in patients with IH-HSBP younger than 65 years was higher than that in patients with IH-HSBP older than 65 years. CONCLUSION: IH-HSBP was associated with an increased risk of diabetic nephropathy among type 2 diabetes mellitus patients with normal or mildly increased albuminuria in the medium to long term. The results support and strengthen previous reports. These findings suggest that IH-HSBP might be a useful marker in disease prognostication.