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Background and Aims Previous studies conducted in Europe suggested that darvadstrocel, a suspension of expanded, allogeneic, adipose-derived, mesenchymal stem cells, is safe and effective for treatment-refractory complex perianal fistulas in patients with Crohn’s disease. The aim of this study was to evaluate the efficacy and safety of darvadstrocel for the treatment of complex perianal fistulas in Japanese adults with Crohn’s disease. Methods This is a phase 3, open-label, single-arm study conducted at nine sites in Japan. Adult patients with non-active or mildly active Crohn’s disease and complex perianal fistulas received a single 24-mL intralesional injection of darvadstrocel [120 × 106 cells]. The primary endpoint was combined remission (clinically confirmed closure of all treated external openings that were draining at screening, and absence of collections >2 cm, [confirmed by magnetic resonance imaging] among treated fistulas) at Week 24. Results Between March 6, 2019 and February 1, 2021, 22 patients received darvadstrocel and completed the 52-week follow-up. The proportion of patients achieving combined remission at Week 24 was 59.1% (95% confidence interval [CI], 38.5–79.6). The effect was maintained at Week 52, with 68.2% [95% CI, 48.7–87.6] of patients achieving combined remission. Treatment-related adverse events included: one [4.5%] patient with worsening of Crohn’s disease and diarrhoea, and one [4.5%] patient with blood bilirubin increase. No new safety findings were identified in this study. Conclusions The efficacy and tolerability of darvadstrocel in Japanese adult patients with treatment-refractory complex perianal fistulas in Crohn’s disease were similar to those observed in the previous European study. ClinicalTrials.gov number, NCT03706456.

Terpenoids are natural compounds originating from five-carbon isoprene units. Over 60,000 terpenoid structures have been identified, and they contribute to the flavor, color, growth, and development of plants. There are several reports on various physiological activities of terpenoids, such as antioxidative and anticancer activities. This study revealed that combinations of terpenoids have activities against a spectrum of bacteria. The combination of carvacrol and thymol has bacteriostatic and bactericidal activities. Four terpenoids (carvacrol, thymol, eugenol, and nootkatone) exhibited bacteriostatic and bactericidal activities when used at low concentrations for 5‒10 min. The most effective bactericidal activity was observed for gram-negative bacteria. A very weak bactericidal activity was observed against Staphylococcus aureus and Enterococcus faecalis. This study revealed the antibacterial potential of different combinations of terpenoids against several bacteria that were tested. Thus, new candidates for the development of antibacterial medicines are reported here for the effective treatment of infectious bacterial diseases.

Venous air embolism (VAE) can be observed in the right heart system on contrast-enhanced computed tomography (CT), following injection of contrast media with a power injector system. Although most VAEs are mostly asymptomatic, they may result in paradoxical air embolism (PAE). To evaluate whether the incidence of VAE on coronary CT angiography is associated with the process of preparation of the intravenous access route. We retrospectively evaluated 692 coronary CT examinations at 3 institutions. Trained CT nurses placed an intravenous cannula in the forearm. Tubes connected to the cannula were prepared in the following ways: A, using an interposed three-way cock and a 20-mL syringe filled with normal saline to collect air contamination in the tube; B, through direct connection to the power injector system without the interposed 3-way cock; and C, using an interposed three-way cock and a 100-mL normal saline drip infusion bottle system to keep the tube patent. The incidence and location of VAE and preparation of intravenous injection were assessed. The overall incidence of VAE was 55.3% (383/692), most frequently observed in the right atrium (81.5%, 312/383). Its incidence varied significantly across the 3 techniques (A: 21.6% (35/162), B: 63.2% (237/375) and C: 71.6% (111/155); P

Focusing on agro-pastoralism and the change in farmland use by the highlanders in Ladakh, Domkhar valley in lower Ladakh was selected as the research site. Domkhar valley has a total population of 1,269 people and 193 households and is divided into three villages based on their locations: Domkhar Do (lower village, 3,000 to 3,100 meters altitude), Domkhar Barma (middle village, 3,400 to 3,500 meters altitude), and Domkhar Gonma (upper village, 3,600 to 4,000 meters altitude). There is a hamlet called Kuramric at the highest point of the upper village at 4,100 meters. The villagers release their livestock in the pastures in the U-shaped valley located above Kuramric. Barley is the main crop cultivated in all three villages. Wheat can be cultivated in the lower and middle villages, but not in the upper village. We created a list of households in the three villages in Domkhar valley before conducting interviews. We then created a map showing irrigation canals, the land ownership and usage of each household from the GeoEye-1 satellite images taken in September and November 2010. We elucidated the change in land use and water management based on this map of irrigation canals, land ownership and usage along with the interviews and on-site observations. For more than 30 years, Ladakhi people has been receiving government rations of cheap flour, rice, sugar, and petroleum in Ladakh where the Sino-Indian Border Conflict and the Indo-Pakistani War were fought. For this reason, their staple food has switched from barley to the rationed flour. The change in the livelihood of agro-pastoralism has brought about changes in the land use, but even in this case, the temperature constraint from the difference in altitude remains a major defining factor in the selection and introduction of cash crops.

Nootkatone is one of the sesquiterpenes contained in citrus peels, especially in grapefruits. It is known that nootkatone has various physiological activities such as antioxidative and antifibrotic actions. This study showed that nootkatone, a natural sesquiterpene, exhibited antibacterial activities against Gram-positive bacteria such as Staphylococcus aureus, Enterococcus faecalis, Listeria monocytogenes, Corynebacterium diphtheriae, and Bacillus cereus, with the antibacterial effect against C. diphtheriae being most pronounced. However, no growth-inhibitory effects or bactericidal activity was observed against Gram-negative bacteria. In addition, the bactericidal activity of nootkatone at a high concentration was observed against Gram-positive bacilli. These results suggested that nootkatone may exert an antibacterial effect by targeting cell wall structures or a particular metabolite. Moreover, even at a low concentration (0.25 mM), nootkatone was capable of inhibiting biofilm formation by Staphylococcus aureus. Thus, this study demonstrated antibacterial efficacy for nootkatone against Gram-positive bacteria, indicating that nootkatone could be a potential candidate for the development of new antibacterial agents.

Objectives: To clarify the association between glucose intolerance and high altitudes (2900-4800 m) in a hypoxic environment in Tibetan highlanders and to verify the hypothesis that high altitude dwelling increases vulnerability to diabetes mellitus (DM) accelerated by lifestyle change or ageing. Design: Cross-sectional epidemiological study on Tibetan highlanders. Participants: We enrolled 1258 participants aged 40-87 years. The rural population comprised farmers in Domkhar (altitude 2900-3800 m) and nomads in Haiyan (3000-3100 m), Ryuho (4400 m) and Changthang (4300-4800 m). Urban area participants were from Leh (3300 m) and Jiegu (3700 m). Main outcome measure: Participants were classified into six glucose tolerance-based groups: DM, intermediate hyperglycaemia (IHG), normoglycaemia (NG), fasting DM, fasting IHG and fasting NG. Prevalence of glucose intolerance was compared in farmers, nomads and urban dwellers. Effects of dwelling at high altitude or hypoxia on glucose intolerance were analysed with the confounding factors of age, sex, obesity, lipids, haemoglobin, hypertension and lifestyle, using multiple logistic regression. Results: The prevalence of DM (fasting DM)/IHG (fasting IHG) was 8.9% (6.5%)/25.1% (12.7%), respectively, in all participants. This prevalence was higher in urban dwellers (9.5% (7.1%)/28.5% (11.7%)) and in farmers (8.5% (6.1%)/28.5% (18.3%)) compared with nomads (8.2% (5.7%)/15.7% (9.7%)) (p=0.0140/0.0001). Dwelling at high altitude was significantly associated with fasting IHG+fasting DM/fasting DM (ORs for >4500 and 3500-4499 m were 3.59/4.36 and 2.07/1.76 vs

The purpose of this study is to clarify the effectiveness of the use of β-blocker in coronary computed tomography angiography (CCTA). In 1783 patients, heart rate was controlled by propranolol injection to patients with heart rates of 61 bpm or more. As a result, the scan heart rate (58.8±6.5 bpm) decreased significantly compared with the initial heart rate (72.7±9.4 bpm). Prospective gating method was used by 61.9% including 64.3% of the intravenous β-blocker injection group. Moreover, daily use of oral β-blocker had influence on reduction of the scan heart rate (daily use group: 60.1±6.5 bpm vs. unuse group: 58.5±6.3 bpm p

The test bolus tracking (TBT) method is a new injection method of contrast medium that we developed. The TBT method is an injection technique that continuously performs the test bolus injection and the main bolus injection, such that the best acquisition of scan timing and the improvement of examination efficiency can be expected. We compared the TBT method and the test injection method by coronary CT angiography. The results demonstrated that the contrast enhancement of the coronary arteries was high and the variation of the CT value was also small in the TBT method. When the scan timing expected by the TI method and the TBT method were compared, it was different of two seconds or more by the case with 43%. However, the variation of CT value was small for the TBT method in these cases. Therefore, the TBT method is a very useful method for CCTA.

Objective Prevalence of hypertension was examined in a widely dispersed (45 110 km 2 ) representative group of Ladakhi in Northern India. The influence of hypoxic environment of wide-ranged altitude (2600–4900 m) and lifestyle change on hypertension was studied. Methods 2800 participants (age 20–94 years) were enrolled. Systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure of ≥90 mm Hg and/or taking current anti-hypertensive medicine was defined as hypertension. Height and weight for body mass index and SpO 2 were examined. The rural population comprised six subdivisions with a distinct altitude, dietary and occupational pattern. Participants in the urban area of Leh consist of two groups, that is, migrants settled in Leh from the Changthang nomadic area, and dwellers born in Leh. The prevalence of hypertension in the two groups was compared with that in the farmers and nomads in rural areas. The effects of ageing, hypoxia, dwelling at high altitude, obesity, modernised occupation, dwelling in an urban area, and rural-to-urban migration to hypertension were analysed by multiple logistic regression. Results The prevalence of hypertension was 37.0% in all participants and highest in migrants settled in Leh (48.3%), followed by dwellers born in Leh town (41.1%) compared with those in rural areas (33.5). The prevalence of hypertension in nomads (all: 27.7%, Tibetan/Ladakhi: 19.7/31.9%)) living at higher altitude (4000–4900 m) was relatively low. The associated factors with hypertension were ageing, overweight, dwelling at higher altitude, engagement in modernised sedentary occupations, dwelling in urban areas, and rural-to-urban migration. The effects of lifestyle change and dwelling at high altitude were independently associated with hypertension by multivariate analysis adjusted with confounding factors. Conclusions Socioeconomic and cultural factors play a big role with the effect of high altitude itself on high prevalence of hypertension in highlanders in Ladakh.