A new method for producing superior set yogurt, focusing on heat treatment and homogenization.

Extended shelf life (ESL) processing (i.e., heat treatment at 130°C for 2 s) is usually not used for producing set yogurt because of the fragility of the curd structure. We investigated the effects of homogenization conducted at higher pressure than the conventional conditions (10 MPa for the first stage and 5 MPa for the second stage) on the curd structure of set yogurt, with a focus on the fat globule size. Each yogurt mix was adjusted at the range of fat globule sizes from 0.45 µm to 1.1 µm by a homogenizer and then heated at 95°C for 5 min (conventional heat treatment), 120°C for 2 s, ESL processing, or 140°C for 2 s. The yogurt mixes were fermented by a common yogurt starter, and the curd texture of the obtained yogurts was evaluated. We observed that the curd hardness and curd firmness of the yogurt were each negatively correlated with the fat globule size regardless of the heat-treatment temperature. Compared with the curd obtained with conventional heat treatment, the ESL-processed curd was extremely fragile, but significantly smooth. With ESL processing, a curd hardness >40 g, which is a sufficient strength for commercial transport systems, was obtained by making the fat particle size <0.6 µm, using 2-stage homogenization pressure: 35 MPa for the first stage and 5 MPa for the second stage. A microscopy analysis indicated that the smaller fat globules reinforce the network structure. The yogurt made by ESL processing and that created with 35 + 5 MPa homogenization had significant sensory evaluation scores. Our results indicate that the combination of ESL processing and 35 + 5 MPa homogenization is a novel and useful method for manufacturing set yogurt.

Simulating complex quantum networks with time crystals.

Crystals arise as the result of the breaking of a spatial translation symmetry. Similarly, translation symmetries can also be broken in time so that discrete time crystals appear. Here, we introduce a method to describe, characterize, and explore the physical phenomena related to this phase of matter using tools from graph theory. The analysis of the graphs allows to visualizing time-crystalline order and to analyze features of the quantum system. For example, we explore in detail the melting process of a minimal model of a period-2 discrete time crystal and describe it in terms of the evolution of the associated graph structure. We show that during the melting process, the network evolution exhibits an emergent preferential attachment mechanism, directly associated with the existence of scale-free networks. Thus, our strategy allows us to propose a previously unexplored far-reaching application of time crystals as a quantum simulator of complex quantum networks.

Faecal freezing preservation period influences colonization ability for faecal microbiota transplantation.

AIMS: There has been growing interest in faecal microbiota transplantation (FMT) as treatment. Although, frozen donor faeces preserved at -20°C has been widely used for practical advantages, freezing at -20°C can affect bacterial viability. Adequacy evaluation of fresh and frozen faeces as the transplant is necessary for the methodological improvement of FMT. METHODS AND RESULTS: The viable bacterial compositions of faecal specimens under fresh and freezing conditions were compared by a microbiome analysis using propidium monoazide (PMA microbiome). In addition, recovery abilities from bacterial reduction by antibiotics were compared between fresh and frozen FMT using a murine model. PMA microbiome results suggested that freezing and freeze-thawing did not significantly affect in vitro faecal bacterial viability. However, the recovery effect from antimicrobial cleansing in frozen FMT was reduced in a freezing time-dependent manner, especially prominent in Actinobacteria and Bacteroidetes phyla. CONCLUSIONS: Short-term freezing preservation of faeces exhibited maintenance of enteric colonization ability in frozen FMT in comparison to 1 month -20°C-preservation. SIGNIFICANCE AND IMPACT OF THE STUDY: Long-term -20°C-preservation of transplanted faeces can result in instability of the clinical outcome in FMT therapy. The standardization of practical procedures of FMT therapy according to disease types is desirable.

Disease-modifying effects of COX-2 selective inhibitors and non-selective NSAIDs in osteoarthritis: a systematic review.

Osteoarthritis (OA) is a potentially disabling disease whose progression is dependent on several risk factors. OA management usually involves the use of non-steroidal anti-inflammatory drugs (NSAIDs) that are the primary pharmacological treatments of choice. However, NSAIDs have often been associated with unwanted side effects. Cyclooxygenase (COX)-2 specific inhibitors, such as celecoxib, have been successfully used as an alternative in the past for OA treatment and have demonstrated fewer side effects. While abundant data are available for the clinical efficacy of drugs used for OA treatment, little is known about the disease-modifying effects of these agents. A previous review published by Zweers et al. (2010) assessed the available literature between 1990 and 2010 on the disease-modifying effects of celecoxib. In the present review, we aimed to update the existing evidence and identify evolving concepts relating to the disease-modifying effects of not just celecoxib, but also other NSAIDs. We conducted a review of the literature published from 2010 to 2016 dealing with the effects, especially disease-modifying effects, of NSAIDs on cartilage, synovium, and bone in OA patients. Our results show that celecoxib was the most commonly used drug in papers that presented data on disease-modifying effects of NSAIDs. Further, these effects appeared to be mediated through the regulation of prostaglandins, cytokines, and direct changes to tissues. Additional studies should be carried out to assess the disease-modifying properties of NSAIDs in greater detail.

Centripetal Propagation of Vasoconstriction at the Time of Headache Resolution in Patients with Reversible Cerebral Vasoconstriction Syndrome.

BACKGROUND AND PURPOSE: Reversible cerebral vasoconstriction syndrome is characterized by thunderclap headache and diffuse segmental vasoconstriction that resolves spontaneously within 3 months. Previous reports have proposed that vasoconstriction first involves small distal arteries and then progresses toward major vessels at the time of thunderclap headache remission. The purpose of this study was to confirm centripetal propagation of vasoconstriction on MRA at the time of thunderclap headache remission compared with MRA at the time of reversible cerebral vasoconstriction syndrome onset. MATERIALS AND METHODS: Of the 39 patients diagnosed with reversible cerebral vasoconstriction syndrome at our hospital during the study period, participants comprised the 16 patients who underwent MR imaging, including MRA, within 72 hours of reversible cerebral vasoconstriction syndrome onset (initial MRA) and within 48 hours of thunderclap headache remission. RESULTS: In 14 of the 16 patients (87.5%), centripetal propagation of vasoconstriction occurred from the initial MRA to remission of thunderclap headache, with typical segmental vasoconstriction of major vessels. These mainly involved the M1 portion of the MCA (10 cases), P1 portion of the posterior cerebral artery (10 cases), and A1 portion of the anterior cerebral artery (5 cases). CONCLUSIONS: This study found evidence of centripetal propagation of vasoconstriction on MRA obtained at the time of thunderclap headache remission, compared with MRA obtained at the time of reversible cerebral vasoconstriction syndrome onset. If clinicians remain unsure of the diagnosis during early-stage reversible cerebral vasoconstriction syndrome, this time point represents the best opportunity to diagnose reversible cerebral vasoconstriction syndrome with confidence.

Difference in efficacy of proton pump inhibitor between new-onset and recurrent gastroesophageal reflux disease: Result from a study of on-demand versus continuous maintenance therapy in Japan.

BACKGROUND-OBJECTIVE: No study has focused on the difference in efficacy of maintenance therapy between patients with new-onset and recurrent gastroesophageal reflux disease (GERD). The aim of this study is to reveal this point. METHODS: Endoscopically proven GERD patients who had completed 8-week initial therapy were sequentially randomized to continuous arm (Omeprazole 20mg od) or on-demand arm (Omeprazole 20mg on-demand). Patients filled in daily symptoms and tablet usages for 24 weeks. Patients underwent upper GI endoscopy at 24 weeks. Symptom relief was defined as no symptoms for>6 days during a week. The numbers of patients who achieved symptom relief and mucosal healing were compared between the new-onset and recurrent groups in the continuous arm and in the on-demand arm, respectively. RESULTS: Among new-onset GERD [n=82 (continuous: 42 patients, on-demand: 40)], continuous arm achieved significant symptom-relief than in on-demand arm at 4*,5*,6** and 17*week. Among recurrent GERD [n=36(continuous: 17 patients, on-demand: 19)], continuous arm achieved significant symptom-relief at 1**,2*,3*,4*,5**,7**,8**,17* and 18* week, respectively (*<0.05,**<0.01). The number of healed patients was significantly higher in new-onset group (60/68, 88.2%) than in recurrent group (17/30, 56.7%) (<0.01). CONCLUSION: Since therapeutic response during maintenance therapy was poor in recurrent GERD, continuous therapy is recommended in order to maintain symptom-relief and mucosal healing. Hippokratia 2015, 19 (1): 53-56.

Creep mechanisms of a new Ni-Co-base disc superalloy at an intermediate temperature.

The microstructures of a new Ni-Co-base disc superalloy, TMW-4M3, before and after the creep test at 725 °C/630 MPa have been systematically investigated by transmission electron microscopy (TEM). The crept microstructures were marked as three different deformation stages (I, II and III) corresponding to the gradually increased strain. At stage I, stacking fault (SF) shearing was the main deformation mechanism. The SF was extrinsic and lay on {111} plane. However, deformation microtwinning became the dominant mode at stage II and III. The average spacing of deformation twins decreased from 109 ± 15 nm at stage II to 76 ± 12 nm at stage III, whereas the twin thickness did not change significantly. The influence of stacking fault energy (SFE) of γ matrix on the deformation mechanism is discussed. It is suggested that lower SFE in TMW-4M3 is partly responsible for the enhanced creep resistance.

Relationship between reduced lower abdominal blood flows and heart rate in recovery following cycling exercise.

AIM: To examine the blood flow (BF) response in the lower abdomen (LAB) in recovery following upright cycling exercise at three levels of relative maximum pulmonary oxygen consumption (VO(2max)) and the relationship of BF(LAB) to heart rate (HR) and target intensity. METHODS: For 11 healthy subjects, BF (Doppler ultrasound) in the upper abdominal aorta (Ao) above the coeliac trunk and in the right femoral artery (RFA) was measured repeatedly for 720 s after the end of cycling exercises at target intensities of 30%, 50% and 85% VO(2max), respectively. Blood flow in the lower abdomen (BF(LAB)) can be measured by subtracting bilateral BF(FAs) (≈twofolds of BF(RFA)) from BF(Ao). Change in BF(LAB) (or BF(LAB) volume) at any point was evaluated by difference between change in BF(Ao) and in BF(FAs). Heart rate and blood pressure were also measured. RESULTS: At 85% VO(2max), significant reduction in BF(LAB) by approx. 89% was shown at 90 s and remained until 360 s. At 50% VO(2max), reduction in BF(LAB) by approx. 33% was found at 90 s although it returned to pre-exercise value at 120 s. On the contrary at 30% VO(2max), BF(LAB) showed a light increase (<20%) below 70 bpm of HR. There was a close negative relationship (P < 0.05) between change in BF(LAB) and recovery HR, as well as between change in BF(LAB) volume and both recovery HR and % VO(2max). CONCLUSION: This study suggests that the lower abdominal BF in recovery may be influenced by sympathetic-vagus control, and dynamics of BF(LAB) may be closely related to the level of relative exercise intensities.

Methylprednisolone reduces postoperative nausea in total knee and hip arthroplasty.

WHAT IS KNOWN AND OBJECTIVE: Total knee and hip joint replacement has a high risk of postoperative nausea and vomiting (PONV), and steroid cover is used for cases associated with autoimmune diseases. Our aim is to evaluate the antiemetic efficacy of methylprednisolone as steroid cover in patients undergoing the surgery. METHODS: A prospective cohort study design was used. Sixty-eight patients, aged between 20 and 80 years, were scheduled for a standardized general anaesthetic technique. Patients who were given methylprednisolone were assigned as the steroid cover group, and those who were not given methylprednisolone formed the non-steroid cover group. PONV were assessment by direct questioning or spontaneous complaints by patients 1 week after surgery. Postoperative pain was evaluated using Visual Analog Scale (VAS) 1 and 3 days after surgery. RESULTS AND DISCUSSION: The incidence of nausea in the steroid cover group was significantly less than that in the non-steroid cover group (adjusted odds ratio, 0·17, P = 0·021), but there was no significant difference in vomiting between the two groups. Postoperative pain VAS score was not significantly different between groups. WHAT IS NEW AND CONCLUSION: In total knee and hip arthroplasty, methylprednisolone is effective in preventing postoperative nausea; however, higher doses of methylprednisolone may be needed to prevent vomiting.

Phase I study of paclitaxel, cisplatin and 5-fluorouracil combination chemotherapy for unresectable / recurrent gastric cancer.

PURPOSE: We investigated the safety of triple combination therapy by addition of Paclitaxel (PTX) to Cisplatin (CDDP) and 5-fluorouracil (5-FU) combination therapy, which was considered the conventional standard therapy for patients with unresectable / recurrent gastric cancer. MATERIAL AND METHODS: The doses of PTX and CDDP were fixed at 80 and 50 mg/m2. They were administered on days 1 and 8, followed by a resting period of 20 days. 5-FU 300 mg/m2 at a maximum dose of 500 mg/m2 was administered at levels 0 and 2, respectively, and the dose was increased by 100 mg/m2 until the maximum tolerated dose (MTD). It was administered on days 1 - 5 and 8 - 12, followed by a resting period of 16 days. RESULTS: Twelve patients enrolled in this study. Of them, three patients were excluded from evaluation because treatment continuation was not feasible. There were 4 leukopenia and 7 neutropenia cases with hematological toxicity at grade 3 or higher. They were observed at all dose levels, but no case showed infection. In terms of non-hematological toxicity at grade 3 or higher, there were two patients with nausea and vomiting and two patients with diarrhea, one patient with mucositis, one patient with anorexia. All patients with non-hematological toxicity at grade 3 or higher were at level 2. The dose-limiting toxicity (DLT) was observed at level 2, and 5-FU at 400 mg (level 1) was adopted. CONCLUSIONS: We proved in this study that PTX, CDDP, and 5-FU combination chemotherapy was a safe treatment.

Metastatic colorectal cancer cells from patients previously treated with chemotherapy are sensitive to T-cell killing mediated by CEA/CD3-bispecific T-cell-engaging BiTE antibody.

BACKGROUND: Novel technologies to redirect T-cell killing against cancer cells are emerging. We hypothesised that metastatic human colorectal cancer (CRC) previously treated with conventional chemotherapy would be sensitive to T-cell killing mediated by carcinoembryonic antigen (CEA)/CD3-bispecific T-cell-engaging BiTE antibody (MEDI-565). METHODS: We analysed proliferation and lysis of CEA-positive (CEA+) CRC specimens that had survived previous systemic chemotherapy and biologic therapy to determine whether they could be killed by patient T cells engaged by MEDI-565 in vitro. RESULTS: At low concentrations (0.1-1 ng ml(-1)), MEDI-565+ T cells caused reduced proliferation and enhanced apoptosis of CEA+ human CRC specimens. High levels of soluble CEA did not impair killing by redirected T cells and there was no increase in resistance to T-cell killing despite multiple rounds of exposure. CONCLUSIONS: This study shows for the first time that metastatic CRC specimens derived from patients previously treated with conventional chemotherapy can be lysed by patient T cells. Clinical testing of cancer immunotherapies, such as MEDI-565 that result in exposure of tumours to large numbers of T cells, is warranted.

The chromosomal constitution of postmitotic neurons, assessed by neuronal nuclear transfer into oocytes and in ES cell lines derived from them.

Spectral karyotyping (SKY) was used to assess the chromosomal constitution of embryos generated by nuclear transfer (NT) of neuronal nuclei (N-NT) or cumulus cell nuclei (C-NT) into oocytes and of their embryonic stem cell derivatives (ntES cells). We detected chromosomal changes during the first mitotic cleavage and in the condensed chromatids of NT embryos. We also found clonal translocations in the ntES cells that were derived from NT embryos cloned from neuronal nuclei. The differentiation potentials of the ntES cells showing chromosomal rearrangements were partly restricted. Our findings indicate that balanced or unbalanced chromosomal translocations can occur in early NT embryogenesis, suggesting that a DNA repair system is activated during both NT embryogenesis and ntES cell establishment. We observed a higher incidence of chromosomal changes in N-NT than in C-NT embryos, which may reflect a higher frequency of double-stranded (ds) DNA breaks in the neuronal genome.

Low-volume muscle endurance training prevents decrease in muscle oxidative and endurance function during 21-day forearm immobilization.

AIM: To examine the effects of low-volume muscle endurance training on muscle oxidative capacity, endurance and strength of the forearm muscle during 21-day forearm immobilization (IMM-21d). METHODS: The non-dominant arm (n = 15) was immobilized for 21 days with a cast and assigned to an immobilization-only group (Imm-group; n = 7) or an immobilization with training group (Imm+Tr-group; n = 8). Training comprised dynamic handgrip exercise at 30% of pre-intervention maximal voluntary contraction (MVC) at 1 Hz until exhaustion, twice a week during the immobilization period. The duration of each exercise session was 51.7 +/- 3.4 s (mean +/- SE). Muscle oxidative capacity was evaluated by the time constant for phosphocreatine recovery (tau(off)PCr) after a submaximal handgrip exercise using (31)phosphorus-magnetic resonance spectroscopy. An endurance test was performed at 30% of pre-intervention MVC, at 1 Hz, until exhaustion. RESULTS: tau(off)PCr was significantly prolonged in the Imm-group after 21 days (42.0 +/- 2.8 and 64.2 +/- 5.1 s, pre- and post-intervention respectively; P < 0.01) but did not change for the Imm+Tr-group (50.3 +/- 3.0 and 48.8 +/- 5.0 s, ns). Endurance decreased significantly for the Imm-group (55.1 +/- 5.1 and 44.7 +/- 4.6 s, P < 0.05) but did not change for the Imm+Tr-group (47.9 +/- 3.0 and 51.7 +/- 4.0 s, ns). MVC decreased similarly in both groups (P < 0.01). CONCLUSIONS: Twice-weekly muscle endurance training sessions, each lasting approx. 50 s, effectively prevented a decrease in muscle oxidative capacity and endurance; however, there was no effect on MVC decline with IMM-21d.

Optimization of vaccine responses with an E1, E2b and E3-deleted Ad5 vector circumvents pre-existing anti-vector immunity.

Recombinant serotype 5 adenovirus (Ad5) vectors lacking E1 expression induce robust immune responses against encoded transgenes in pre-clinical models, but have muted responses in human trials because of widespread pre-existing anti-adenovirus immunity. Attempts to circumvent Ad5-specific immunity by using alternative serotypes or modifying capsid components have not yielded profound clinical improvement. To address this issue, we explored a novel alternative strategy, specifically reducing the expression of structural Ad5 genes by creating E1 and E2b deleted recombinant Ad5 vectors. Our data show that [E1-, E2b-]vectors retaining the Ad5 serotype are potent immunogens in pre-clinical models despite the presence of significant Ad5-specific immunity, in contrast to [E1-] vectors. These pre-clinical studies with E1 and E2b-deleted recombinant Ad5 vectors suggest that anti-Ad immunity will no longer be a limiting factor, and that clinical trials to evaluate their performance are warranted.

High-frequency electron spin resonance system using a microcantilever and a pulsed magnetic field.

A novel technique of high-frequency electron spin resonance (ESR) in a pulsed magnetic field is presented. Our technique is based on the magnetic detection of a magnetization change associated with the ESR absorption using a microcantilever. We successfully observed ESR signals of a microcrystal (mass approximately 1 microg) in the millimeter-wave region up to 130 GHz in pulsed magnetic fields of up to 2.4 T. This result corresponds to the spin sensitivity of approximately 10(11) spins/G, which is four orders of magnitude better than that of conventional transmission-type ESR techniques.