Ribbon concordance and the minimality of tight fibered knots

Agol proved that ribbon concordance forms a partial ordering on the set of knots in the $3$-sphere. In this paper, we prove that all tight fibered knots are minimal in this partially ordered set. We also give the table of prime minimal knots up to $8$-crossings except for $8_{15}$.Comment: 6 pages, 1 figure, comments are welcome

Association of initial lactate levels and red blood cell transfusion strategy with outcomes after severe trauma: a post hoc analysis of the RESTRIC trial

Background The appropriateness of a restrictive transfusion strategy for those with active bleeding after traumatic injury remains uncertain. Given the association between tissue hypoxia and lactate levels, we hypothesized that the optimal transfusion strategy may differ based on lactate levels. This post hoc analysis of the RESTRIC trial sought to investigate the association between transfusion strategies and patient outcomes based on initial lactate levels. Methods We performed a post hoc analysis of the RESTRIC trial, a cluster-randomized, crossover, non-inferiority multicenter trials, comparing a restrictive and liberal red blood cell transfusion strategy for adult trauma patients at risk of major bleeding. This was conducted during the initial phase of trauma resuscitation; from emergency department arrival up to 7 days after hospital admission or intensive care unit (ICU) discharge. Patients were grouped by lactate levels at emergency department arrival: low ( Results Of the 422 RESTRIC trial participants, 396 were analyzed, with low (n = 131), middle (n = 113), and high (n = 152) lactate. Across all lactate groups, 28 days mortality was similar between strategies. However, in the low lactate group, the restrictive approach correlated with more ICU-free (β coefficient 3.16; 95% CI 0.45 to 5.86) and ventilator-free days (β coefficient 2.72; 95% CI 0.18 to 5.26) compared to the liberal strategy. These findings persisted even after excluding patients with severe traumatic brain injury. Conclusions Our results suggest that restrictive transfusion strategy might not have a significant impact on 28-day survival rates, regardless of lactate levels. However, the liberal transfusion strategy may lead to shorter ICU- and ventilator-free days for patients with low initial blood lactate levels

Antiatherogenic effect of pioglitazone in type 2 diabetic patients irrespective of the responsiveness to its antidiabetic effect

WSTĘP. Tiazolidinediony (TZD) to grupa leków zwiększających wrażliwość na insulinę, które stosuje się w leczeniu cukrzycy typu 2. Działają one także przeciwmiażdżycowo. Celem badania było wyjaśnienie zależności między przeciwmiażdżycowym a przeciwcukrzycowym działaniem pioglitazonu, leku z grupy TZD, u chorych na cukrzycę typu 2. MATERIAŁ I METODY. W badaniu wzięło udział 136 chorych na cukrzycę typu 2 narodowości japońskiej. Uczestników podzielono na 2 grupy: chorych leczonych pioglitazonem w dawce 30 mg na dobę przez 3 miesiące (n = 70) oraz pacjentów niepoddanych leczeniu (grupę kontrolną, n = 66). Podczas badania kontrolowano zmiany metabolizmu glikolipidów, stężenia w osoczu białka C-reaktywnego (CRP, C-reactive protein), leptyny i adiponektyny oraz prędkość fali tętna (PWV, pulse-wave velocity), aby przeanalizować zależność między przeciwmiażdżycowym a przeciwcukrzycowym działaniem pioglitazonu. WYNIKI. U osób leczonych pioglitazonem stwierdzono istotne obniżenie hiperglikemii, hiperinsulinemii i stężenia HbA1c oraz wzrost stężenia adiponektyny w osoczu w porównaniu z grupą kontrolną (p < 0,01). Ponadto, odnotowano istotne obniżenie stężenia CRP i PWV (p < 0,01). Przeciwmiażdżycowe działanie pioglitazonu zaobserwowano zarówno u pacjentów, u których nie uzyskano poprawy wyrównania cukrzycy, a redukcja stężenia HbA1c wynosiła poniżej 1% (n = 30) (nonresponders, osoby niepodatne na leczenie), jak i u chorych z dobrą odpowiedzią na terapię (responders, osoby podatne na leczenie), u których redukcja stężenia HbA1c przekraczała 1% (n = 40). Stosując model ANCOVA wykazano, że leczenie pioglitazonem wiązało się z niskimi wartościami CRP i PWV, niezależnie od zmian parametrów związanych z metabolizmem glukozy. WNIOSKI. W omawianym badaniu po raz pierwszy przedstawiono przeciwmiażdżycowe działanie pioglitazonu zarówno u chorych podatnych, jak i niepodatnych na przeciwcukrzycowe działanie leku. Wyniki badania sugerują, że pioglitazon może wywierać efekt przeciwmiażdżycowy niezależnie od wpływu na glikemię.INTRODUCTION. Thiazolidinediones (TZD), a class of insulin-sensitizing agents used clinically to treat type 2 diabetes, are also antiatherogenic. This study was designed to elucidate the relationship between the antiatherogenic and antidiabetic effects of pioglitazone, a TZD, in type diabetic patients. MATERIAL AND METHODS. A total of 136 Japanese type 2 diabetic patients were included and divided into two groups: the pioglitazone-treated group (30 mg daily 3 months) (n = 70) and the untreated control group (n = 66). The changes in glycolipid metabolism as well as plasma high-sensitivity C-reactive protein (CRP), leptin, adiponectin, and pulse wave velocity (PWV) were monitored to analyze the relationship between the antiatherogenic and antidiabetic effects of pioglitazone. RESULTS. The pioglitazone treatment significantly reduced hyperglycemia, hyperinsulinemia, and HbA1c levels and increased plasma adiponectin concentrations relative to the control group (P < 0.01). It also significantly decreased CRP and PWV (P < 0.01). The antiatherogenic effect was observed in both the nonresponders showing < 1% of reduction in HbA1c (n = 30) and responders showing > 1% of reduction (n = 40). ANCOVA revealed that treatment with pioglitazone was associated with a low CRP and PWV, independent of the changes in parameters related to glucose metabolism. CONCLUSIONS. This study represents the first demonstration of the antiatherogenic effect of pioglitazone in both nonresponders and responders with respect to its antidiabetic effect and suggests that pioglitazone can exert its antiatherogenic effect independently of its antidiabetic effect

Direct Metagenomic Detection of Viral Pathogens in Nasal and Fecal Specimens Using an Unbiased High-Throughput Sequencing Approach

With the severe acute respiratory syndrome epidemic of 2003 and renewed attention on avian influenza viral pandemics, new surveillance systems are needed for the earlier detection of emerging infectious diseases. We applied a “next-generation” parallel sequencing platform for viral detection in nasopharyngeal and fecal samples collected during seasonal influenza virus (Flu) infections and norovirus outbreaks from 2005 to 2007 in Osaka, Japan. Random RT-PCR was performed to amplify RNA extracted from 0.1–0.25 ml of nasopharyngeal aspirates (N = 3) and fecal specimens (N = 5), and more than 10 µg of cDNA was synthesized. Unbiased high-throughput sequencing of these 8 samples yielded 15,298–32,335 (average 24,738) reads in a single 7.5 h run. In nasopharyngeal samples, although whole genome analysis was not available because the majority (>90%) of reads were host genome–derived, 20–460 Flu-reads were detected, which was sufficient for subtype identification. In fecal samples, bacteria and host cells were removed by centrifugation, resulting in gain of 484–15,260 reads of norovirus sequence (78–98% of the whole genome was covered), except for one specimen that was under-detectable by RT-PCR. These results suggest that our unbiased high-throughput sequencing approach is useful for directly detecting pathogenic viruses without advance genetic information. Although its cost and technological availability make it unlikely that this system will very soon be the diagnostic standard worldwide, this system could be useful for the earlier discovery of novel emerging viruses and bioterrorism, which are difficult to detect with conventional procedures

Drug/polymer nanoparticles prepared using unique spray nozzles and recent progress of inhaled formulation

Inhaled formulations are promising for pulmonary and systemic non-pulmonary diseases. Functional engineered particles including drugs and drug-loaded nanocarriers have been anticipated because they can improve drug delivery efficacy against target sites in the lungs or blood. In this review, unique spray nozzles (e.g., four-fluid spray nozzle and two-solution mixing type nozzle) for the preparation of nanocomposite particles which mean microparticles containing drug nanoparticles are described. These nozzles can produce nanocomposite particles in one-step and their spray drying system is suitable for scaling-up. Nanocomposite particles are useful in improving drug absorption and delivery efficacy against alveolar macrophages. In addition, recent studies on several pulmonary diseases (tuberculosis, lung cancer, cystic fibrosis, pneumonia, vaccine and others) and related inhaled formulations were also reviewed