The effect of inspiratory muscle training was to reduce the weaning period by 1.7 days (95% CI 0.4 to 3.0), as presented in Table 4, with individual data in Table 5 (see eAddenda for Table 5). Prior to the weaning period, the controlled ventilation period (see Table 1) accounted for approximately half of the total ventilation period. A Kaplan-Meier analysis of the total intubation time (ie, the controlled ventilation period plus the weaning period) did not identify a significant difference between the experimental and control groups (p = 0.72, see Figure 2.) Although we screened GS-1101 clinical trial 198 patients in the intensive care unit, a large proportion of these critically ill patients

died or were tracheostomised either before or after commencing weaning. This is typical of research in inspiratory muscle training in the intensive care setting (Caruso et al 2005, Chang et al 2005a, How et al 2007, Sprague and Hopkins 2003). This loss to follow-up was one limitation of the study. It was compounded by the wide variability in the condition of these patients, including modifications to their medication regimen, psychological state, haemodynamic stability, and degree of sepsis. Nevertheless,

the sample size remained sufficient for statistically significant between-group differences to be identified selleck inhibitor on several outcomes. Another limitation of the study was the lack of blinding. However, because informed consent was provided by the relatives of these critically ill patients, the potential for placebo and Hawthorne effects to operate within the patients was reduced. Previous research suggests that imbalance between the ventilatory load and the strength and endurance of the respiratory muscles is an important determinant of dependence on mechanical ventilation. For example, patients who have success in weaning have a significantly higher maximal inspiratory pressure than those who do not wean successfully (Epstein et al 2002). This relationship is also reflected in our data, with

the experimental group showing both a significant increase in maximal ADP ribosylation factor inspiratory pressure and a reduction in the weaning period when compared to the control group. Our findings that inspiratory muscle training improved both inspiratory muscle strength and the weaning process are also similar to the findings of several other case series. Martin and colleagues (2002), Sprague and Hopkins (2003), and Chang and colleagues (2005b) delivered inspiratory muscle training to tracheostomised patients with a long-standing dependence on mechanical ventilation. All of these patients showed improved inspiratory muscle strength and almost all weaned successfully within several weeks of starting the training.

8, containing 4% (w/v) SDS, 10% (w/v) glycerol, 5% (v/v) 2-mercaptoethanol and 0.002% (w/v) bromophenol blue] and then boiled for 5 min. SDS-polyacrylamide gel electrophoresis (SDS-PAGE, 10%) and subsequent gel staining with coomassie blue were used for detection of protein expression. The fusion protein was purified from IPTG-induced bacteria in denaturing conditions via a standard nickel resin purification protocol (Qiagen, Valencia, CA). In-gel digestion with trypsin and protein identification via nano-liquid chromatography–linear ion trap quadrupole mass spectrometry (Nano-LC–LTQ-MS) analysis (Thermo Electron Corp., Waltham, MA) were performed following the protocols described previously

[24]. After IPTG induction, E. coli harboring the expression vector with inserted FomA gene [E. Hydroxychloroquine datasheet coli BL21(DE3) FomA] were spread on a sterilized surface and irradiated with UV at total

energy of 7000 J/m2 by an UV cross-linker (Spectronics, Westbury, NY). The viability of UV-irradiated E. coli was determined by observing the growth of bacterial colonies on LB agar plates. For immunization, female ICR (Institute of Cancer Research) mice (3–6 weeks old; Harlan, Indianapolis, IN) were intranasally immunized by inoculating 25 μl of UV-irradiated E. coli BL21(DE3) FomA (108 CFU) into the nasal cavity of each mouse for 9 weeks at a 3-week interval. The second and third inoculations were administered GDC-0973 datasheet in the same manner as the first immunization. Mice immunized with an UV-irradiated E. coli harboring expression vector for green fluorescence protein (GFP) [E. coli BL21(DE3) GFP] (108 CFU) served as a control group. The concentrations of purified recombinant FomA and GFP were determined

by a Bradford else assay (Bio-Rad, Hercules, CA). The sample (25 μg) was electrophoresed in a 10% (w/v) SDS-PAGE and electrophoretically transferred onto a polyvinylidene fluoride (PVDF) membrane (Millipore, Billerica, MA) for 90 min at a current of 75 V. The membrane was pre-incubated in Tris-buffered saline [with 0.1% (v/v) Tween 20] containing 5% (w/v) skim milk, and then incubated at 4 °C overnight with serum (1:1000 dilution) obtained from mice immunized with UV-irradiated E. coli BL21(DE3) FomA or GFP for 9 weeks. Bound antibodies (IgG) were detected with anti-mouse horseradish peroxidase (HRP)-conjugated IgG (1:5000 dilution, Promega, Madison, WI). The peroxidase activity was developed with a western lighting chemiluminescence kit (PerkinElmer, Boston, MA). To induce gum swelling and abscesses, the immunized mice were inoculated with live bacteria as previously described [25]. Briefly, an aliquot of 100 μl of live F. nucleatum (4 × 108 CFU/2 ml in PBS), P. gingivalis (103 CFU/1 ml in PBS) or F. nucleatum plus P. gingivalis (4 × 108 CFU plus 103 CFU/3 ml in PBS) were suspended in 100 μl of PBS, and then inoculated into the oral cavities of immunized mice everyday for 3 days.

Même dans cette population, l’indication de l’EE ne doit pas être systématique mais réfléchie. Les facteurs de décision reposent surtout sur le risque cardiovasculaire du sujet et sur le type de pratique sportive souhaitée. Ainsi si une EE est rarement indiquée pour pratiquer de la randonnée, elle est justifiée chez le compétiteur Selleck ZD1839 qui présente un risque cardiovasculaire élevé. Le

risque cardiovasculaire est évalué par des formules validées, telles celles de Framingham ou SCORE. L’intensité de l’exercice est arbitrairement classée comme faible si elle n’induit pas d’essoufflement ou un essoufflement minime, modérée lorsqu’elle est associée à un essoufflement non désagréablement ressenti et capable d’être supporté pendant plus d’une heure, et enfin élevée si l’essoufflement marquée limite nettement la possibilité de converser et est ressenti désagréablement avec CHIR-99021 datasheet impossibilité de maintenir l’effort longtemps. En résumé, une EE est conseillée à tout sujet désireux de pratiquer un sport intense en compétition (compétition sous-entend toujours sport intense) ou non, et ayant au moins deux facteurs de risque cardiovasculaire. Vis-à-vis du sport intense,

certains facteurs pèsent plus lourds que d’autres. Le tabagisme actif, les dyslipidémies marquées, le diabète ancien, comme l’âge > 60 ans chez l’homme, représentent sûrement un risque marqué [29]. L’inactivité physique et la sédentarité ont un rôle favorisant majeur de survenue d’accident, rôle direct par altération des qualités vasomotrices artérielles et indirect en faisant le lit des facteurs de risque cardiovasculaires, surtout hypertension artérielle et troubles métaboliques, rappelés précédemment. first À l’inverse, la pratique de longue date d’une activité physique au moins modérée régulière représente un point positif. On voit donc que l’indication de l’EE est loin d’être systématique après 35 à 40 ans, comme c’est encore trop souvent le cas. Les indications de

l’EE pour un sédentaire désirant reprendre une activité physique ou pour un sujet entraîné souhaitant poursuivre sa pratique sont résumées sur les Figure 2 and Figure 3. En dehors de quelques situations particulières, le calendrier de suivi des EE est encore mal précisé. Pour les sportifs inscrits sur les listes de haut niveau, l’épreuve d’effort à visée diagnostique doit légalement être répétée au moins tous les 4 ans. Certaines ligues professionnelles imposent une répétition plus fréquente. Pour les sportifs ayant une cardiopathie qui pratiquent une activité sportive adaptée, la répétition de l’EE est en règle générale annuelle. Chez le sportif asymptomatique, l’absence d’étude et la diversité d’expression des cardiopathies, souvent silencieuses, limitent la possibilité de proposer des recommandations.

L’antibiothérapie est inutile en dehors d’une Dolutegravir manufacturer surinfection patente. Elle correspond à une incarnation postérieure et est souvent prise à tort pour une infection [13] and [14]. Elle se rencontre surtout chez les femmes. La physiopathologie est complexe. Après un arrêt brutal de la pousse unguéale liée à un traumatisme ou des microtraumatismes,

la tablette unguéale n’est pas éliminée par le nouvel ongle et plusieurs couches d’ongle s’accumulent sous le repli postérieur induisant une inflammation de ce dernier. Le diagnostic est clinique : elle se manifeste par un épaississement de la partie proximale de la tablette unguéale, un arrêt de la croissance unguéale, une inflammation douloureuse du repli proximal avec apparition secondaire d’un tissu de granulation sous le repli sus-unguéal. Le traitement consiste en l’avulsion proximale de la tablette unguéale. Au tout début, une corticothérapie locale forte ou une injection de corticoïdes dans le repli postérieur peuvent suffire. l’auteur déclare ne pas avoir de conflits d’intérêts en relation avec cet article. “
“Les souches d’E. coliisolées chez des patients sondés à demeure ou en institution étaient statistiquement plus à risque d’être résistantes aux fluoroquinolones. Les souches

isolées parmi les bactériuries liées au soin étaient significativement plus souvent des bactéries à Gram positif et étaient significativement plus souvent résistantes aux fluoroquinolones. Selleckchem PCI-32765 “
“La prise en charge des troubles urologiques chez des patients atteints de maladies neurologiques a été bien décrite dans les recommandations

internationales et nationales des sociétés savantes. Le suivi des patients ayant une vessie neurologique par les urologues et les médecins MPR est généralement proche des recommandations nationales et internationales. “
“Les antithyroïdiens de synthèse (ATS) constituent le traitement de premier choix de la maladie de Basedow en France et en Europe. À titre de préparation à la chirurgie ou l’iode 131, ils sont utilisés aussi dans les hyperfonctionnements thyroïdiens liés aux Sitaxentan nodules toxiques, aux goitres multinodulaires secondairement toxiques. Ils ont également des indications dans d’autres variétés d’hyperthyroïdie, notamment en relation avec les surcharges iodées. Les difficultés actuelles d’approvisionnement en certains ATS conduisent les prescripteurs à s’interroger sur les utilisations comparatives de ces médications. La réflexion porte sur les médications disponibles, leur puissance relative, leurs effets indésirables, les recommandations concernant leur surveillance. Les avis ici formulés ont été recueillis au nom de la Société française d’endocrinologie et du Groupe de recherche sur la thyroïde. En France, ce sont : • d’une part, les imidazolines : thiamazole (Thyrozol®, Laboratoire Merck-Lipha) et carbimazole (Néomercazole®, distribué par CSP).

The measles vaccine is given at 9 months (38 weeks to 12 months). Coverage

was determined at the end of follow-up. In Uganda, vitamin A supplementation is part of the Expanded selleck kinase inhibitor Program on Immunization [15], and was also assessed. Vaccination timeliness was analysed with Kaplan–Meier time-to-event analysis in line with Laubereau et al. [16]. Vaccination data and dates of birth were gathered from the children’s health cards. Vaccination information based on maternal recall was also collected, but the data from the health cards are regarded to be of better quality. Thus, the health card information has been used for analysis when available. Most vaccinations were dated in the health cards, but when vaccinations were registered without a date, we assumed Alectinib research buy that the age when the children were given the specific vaccines was similar as for those with dated vaccinations. The confidence intervals were estimated with Greenwood’s pointwise method. To investigate determinants of timely vaccination, we used cluster adjusted Cox regression analysis. As the Cox regression model evaluated timeliness which has an accepted time range, there will be several ties (with the same vaccination time). We used the exact partial-likelihood method for handling ties to improve model robustness. The assumption of proportional

hazards was checked with Schoenfeld residuals, both graphically, with a significance test, and using a piecewise regression method. Tied cases were handled

with the exact partial-likelihood method. Rational interactions were evaluated and were included in the model only if they had significant and meaningful effects. Log linearity was checked with plotting of Martingale residuals for the complete model vs. a model with one omitted variable. No variables were strongly correlated with each other. We present a univariable as well as a multivariable model, the latter using stepwise selection with removal of covariates when p > 0.1. Socioeconomic wealth index was constructed with the use of multiple correspondence analysis based on ownership of assets as furniture and household characteristics including electricity, a water source, roof material and toilet type. This method is analogous to principal component analysis, and better suited for categorical data L-NAME HCl [17]. The children’s families were grouped into quintiles on the basis of socioeconomic rank. Ethical approval was granted by Makerere University Medical School Research, Ethics Committee and the Uganda National Council for Science and Technology, and Regional Committees for Medical and Health Research Ethics, Western Norway. Signed or thumb-printed informed consent was obtained from each mother prior to study participation. The consent procedure was approved by the ethical committees. A health card was seen for 750 (98%) of the 765 participants.

As depicted in Fig. 1, the 2007 outbreak strains formed a distinct cluster within G9 VP7 Lineage III, sub-lineage D. The strains in Lineage III exhibited 93.3-99.1% nucleotide identity

to the Alice Springs outbreak samples. The 2007 outbreak strains exhibited closest similarity to a G9P[8] strain isolated in Brazil in 2006, with 99.0–99.1% nucleotide similarity and 99.8–99.9% amino acid identity. BVD-523 manufacturer Comparison of the deduced amino acid sequences of the VP7 genes from the 2007 outbreak strains with VP7 from G9P[8] strains previously identified in Australia also revealed a close relationship with the previous circulating Australian G9P[8] strains in Lineage III, with a 98.0–98.7% nucleotide and 94.0–96.3% amino acid sequence similarity observed. Three conserved amino acid substitutions were identified at positions 44 (Ala/Val-Thr), 263 (Val-Ile) and 279 (Ala-Thr) in the KU-57788 ic50 2007 outbreak strains when compared to other G9 strains analysed. A 663 bp region of the VP8* subunit of the VP4 gene was sequenced for six G9P[8] samples, including three from vaccinated infants.

The sequences were highly conserved with 99.6–100% nucleotide identity and 98.7% amino acid homology observed. No conserved nucleotide or amino acid changes were observed between samples obtained from vaccinated and non-vaccinated patients. Phylogenetic analysis of the nucleotide sequence of the VP8* subunit of the G9P[8] 2007 outbreak strains and previously published P[8] human strains was performed. As depicted in Fig. 2, found the 2007 outbreak strains formed a distinct cluster within P[8] Lineage 3 (P[8]-3). The strains in P[8] Lineage 3 exhibited 97.3–99.7%

nucleotide identity to the Alice Springs outbreak samples. The 2007 outbreak strains revealed close similarity to G9P[8] strains isolated in the USA, Russia and Ireland, displaying 98.6–99.3% nucleotide and 97.0–99.1% amino acid identity. When compared to a 2001 Australian G9P[8] isolate, the outbreak strains exhibited 98.3–98.6% nucleotide and 97.8–98.7% amino acid identity. The 2007 outbreak strains contained two unique amino acid substitutions at positions 237 (Ser-Leu) and 242 (Thr-Ser) when compared to all other P[8] strains analysed. The 750 bp of the NSP4 gene was sequenced for 14 G9P[8] outbreak strains including three from vaccinated infants. The sequences were all highly conserved displaying 99.4–100% nucleotide and 99.9–100% amino acid identity. No conserved changes were observed between samples obtained from vaccinated and non-vaccinated patients. Phylogenetic analysis of the nucleotide sequence of the NSP4 gene of the G9P[8] 2007 outbreak strains and previously published NSP4 genes was performed. As depicted in Fig. 3, the NSP4 from the 2007 outbreak strains formed a distinct cluster within the E1 Genogroup. The strains in E1 Genogroup exhibited 90.6–99.

21, 95% CI 0.05 to 0.85), reduced the duration of ventilatory assistance (MD –2.0 days, 95% CI –1.5 to –2.6) and reduced overall hospital length of stay (MD –0.75 days, 95% CI –0.1 to –1.4).43 These results were heavily influenced by trials using positive pressure techniques, which generally had more favourable outcomes than those that did not use positive pressure. In addition to the Cochrane review,44 there are two large trials of airway clearance techniques for AECOPD that have implications Crizotinib concentration for practice. A randomised controlled equivalence trial in 526 people hospitalised

with an AECOPD found no difference in quality of life at 6 months between those who received manual chest physiotherapy (active cycle of breathing technique including FET, percussion and vibration) and those who received only advice about positioning and active cycle of breathing technique.44 There was no difference in hospital length of stay between groups. The trial had broad inclusion criteria and participants did not have to be productive of sputum to take part. The

results of this study provide confidence that manual chest physiotherapy techniques do not have a routine role for people with AECOPD. Another randomised trial comparing positive expiratory pressure therapy (PEP) and FET to usual physiotherapy care in 90 people hospitalised with AECOPD found no difference between groups in the primary outcome – the Breathlessness,

Cough and Sputum Scale – at any time point during the 6-month followup.45 Although dyspnoea improved more rapidly in the PEP group in the first 8 Erlotinib solubility dmso weeks, by 6 months there were no clinically relevant or statistically significant differences between groups. When this trial is combined with previous airway clearance technique studies in a meta-analysis, the body of evidence no longer suggests an overall benefit of the techniques during AECOPD in the need for ventilatory assistance (Figure 2; for a more detailed forest plot, see Figure 3 on the eAddenda).45, 46, 47, 48 and 49 The differing results between this trial and previous studies may be related to the population studied, which included fewer people who needed ventilatory assistance, or to the more active comparison group, where usual physiotherapy care included early mobilisation.49 In summary, current evidence those for the effects of airway clearance techniques in AECOPD is inconsistent across trials, but does not suggest an overall benefit of airway clearance techniques for hospitalised patients. Whilst positive outcomes have been reported in the sickest patients (ie, those requiring or at risk of requiring invasive or non-invasive ventilatory assistance) in the most recent Cochrane review,43 these effects are small and are not supported by the results of a recent large trial.49 There is no evidence that manual chest physiotherapy techniques are useful in AECOPD.

3). Previous data suggested that the mucosal immunity induced by parenteral delivery of VRP may be due

to the induction of a mucosal-like environment in the draining lymph node [29]. It is therefore possible that there are long-term effects in the lymph node after prime with VRP which affect the immune response during boost. In addition, it was unknown whether VRP play a more important role during prime or boost, or if both are equally important. We addressed these questions in mice which received a prime and boost with OVA in the footpad. These mice were divided into groups which received no VRP, VRP in prime only, VRP Alectinib research buy in boost only, VRP in both prime and boost, or VRP and OVA in the contralateral footpad during boost. We performed these studies in the footpad instead of i.m., so that the injection would drain to a single lymph node, focusing any effects. A low VRP dose (103 IU) was used to minimize possible effects of VRP in other lymph nodes. Evaluation of anti-OVA IgG in the serum and IgA in fecal extracts demonstrates

a comparable adjuvant effect in mice receiving the boost in the same or contralateral footpad as in prime (Fig. 4A and B). The OVA-specific IgG titer was similarly increased when VRP was included in prime only (Fig. 4A). However, when VRP was present only in the boost, the IgG titer was increased but to a significantly lower level. A more dramatic effect was observed for fecal anti-OVA IgA. Mice receiving VRP only during the boost had no detectable anti-OVA IgA, but addition of VRP to the prime only induced an www.selleckchem.com/btk.html IgA response comparable to that seen in mice immunized with VRP during both prime and boost (Fig. 4B). After prime with antigen and VRP, we do not observe any mucosal response without an antigen boost (data not shown), so it is apparent that boost with antigen is still required to generate an IgA response. Previous studies

of VRP activity have evaluated events in the draining lymph node after boost [29]. Since the events which occur during prime are clearly crucial for the VRP adjuvant activity (Fig. 4), we examined the cytokine environment in the draining lymph node 6 h after prime with VRP by multiplex very analysis. We again used footpad rather than intramuscular injection because this route allows us to focus our analysis on a single lymph node. We first measured levels of 30 cytokines in draining popliteal lymph nodes harvested 6 h after footpad injection with OVA (10 μg) or with OVA combined with 104 IU VRP. In VRP-injected mice we observed a significant increase in 18 of the 30 measured cytokines (Table 1). Based on the collected data, we selected a panel of 10 cytokines, 9 of which had a large fold increase in response to VRP, and one negative control (IL-12p40). We assessed those cytokine levels after injection of OVA alone or OVA with a range of VRP doses between 101 and 105 IU.

Such selleck professional advances bring greater responsibilities in providing health information. Indeed, continued recognition as important and highly skilled health professionals demands that we deliver reliable and accurate health information to our patients and stakeholders so that they can make informed decisions about their healthcare. Effective information exchange is particularly important in physiotherapy practice since this constitutes a fundamental component of most patient-practitioner encounters (Liddle et al 2009), particularly in the context of self-management. In order to do this effectively, we must consider how this

information is made available and the manner in which it is delivered, and ultimately understood. As the requirement for self-management in healthcare is increasingly emphasised, especially in the management of chronic conditions, patients are asked to assume greater responsibility in: • handling diverse information resources such as educational materials, prescriptions and medical forms; To

undertake these tasks effectively, patients require a basic set of skills which enable them to seek, understand, and utilise health information, a concept referred to as health literacy ( USA Department of Health and Human Lonafarnib Services 2000). This editorial outlines the importance and relevance of health literacy to physiotherapy practice and potential ways to optimise the exchange of information during the physiotherapist-patient encounter. Myriad definitions of healthy literacy exist, leading to

debate as to what health literacy represents and how it should be measured. However, across definitions there is a consistent theme that patients require a distinct set of abilities to seek, understand, and use health information. Some definitions focus on literacy and numeracy skills, while others encompass broader attributes such as conceptual and cultural knowledge, and social skills. Increasingly, health literacy is recognised as a complex multidimensional Resveratrol concept that involves interaction between patient abilities and broader social, environmental, and healthcare factors (Jordan 2010a). Low health literacy has been linked to poor health behaviours and outcomes, independent of other sociodemographic factors (DeWalt et al 2004). It is therefore recognised as an important public health issue both in Australia and internationally. For example, a recent report concluded that low health literacy skills increased national annual healthcare expenditures by $US73 billion (USA National Academy on an Aging Society 1999).

A modified bilateral transfrontal sinus approach [45] was made with an air-powered high-speed drill (Hall Micro 100 drill 5053-09, Zimmer-Hall, Warsaw, IN) and oscillating saw cooled by continuous lavage with isotonic saline solution. The dura was sharply incised and reflected to expose the right frontal lobe. Pial vessels were cauterized with bipolar electrocoagulation and the neoplastic tissue was excised using blunt and sharp dissection and suction INCB28060 molecular weight aspiration. Tumor samples were placed in culture media in preparation for isolation and culture of brain tumor cells for vaccine production

and in 10% formalin for processing for histopathology. Immediately following tumor debulking, 6.0 × 108 infectious units of Ad-IFNγ were administered into the resection cavity by 28 injections (2 μl/site, 1–2 cm deep) covering the circumference of the cavity. Ad-IFNγ, encoding human IFNγ regulated by the CMV promoter, was produced as previously described [46]. The dura was closed. Gelatin sponges (Gel Foam, Upjohn Co., Kalamazoo, this website MI) were placed over the dura, and the bone flap was replaced. Then the subcutaneous tissues and skin were closed over the craniotomy. The dog recovered

from anesthesia in the intensive care unit and was monitored for seizure activity until discharged from the hospital. The dog received hydromorphone (0.05 μg/kg SC QID) for analgesia, methylprednisolone sodium succinate (15 mg/kg IV 12 h and 7.5 mg/kg IV 24 h after surgery), and phenobarbital (1.5 mg/kg IV BID) as an anticonvulsant in the ICU. After discharge, phenobarbital (1.5 mg/kg PO BID) much was continued, a tapering dose of prednisolone (1 mg/kg PO BID × 3 days, 0.5 mg/kg PO BID × 3 days, 0.5 mg/kg PO EOD × 3 days), and morphine sulfate SR (1 mg/kg PO BID × 3 days) were administered. Autologous and allogeneic canine astrocytoma cells used for vaccination were grown in DMEM/F12 media supplemented with N2, B27 (Invitrogen,

Carlsbad, CA) and 20 ng/ml of human epidermal growth factor and basic fibroblast growth factor (Peprotech, Rocky Hill, NJ). The allogeneic cells were derived from a French bulldog. The tumors used to make cell cultures were dissociated as previously described [18]. Cells were cultured at 37 °C, 5% O2, 5% CO2 in a humidified incubator in 10 cm dishes or 75 cm2 flasks. All vaccinations were prepared as follows. Cells were harvested, washed thrice in PBS, and resuspended in 200 μl PBS. Lysates were generated by the freeze thaw method as previous described [14] and lysates were further irradiated at 200 Gy to ensure complete tumor cell death. Each vaccine administered consisted of an average of 536 μg of protein lysate (range 230–641 μg) mixed with 2 mg of phosphorothioated-unmethylated type-B CpG ODN 685 (5′-tcgtcgacgtcgttcgttctc-3′; SBI Biotech, Japan).