Association of Pharmacist-led Deprescribing Intervention with the Functional Recovery in Convalescent Setting.

So far, no studies investigated the association between pharmacist intervention and rehabilitation outcomes. The aim of study was to establish whether the pharmacist-led deprescribing intervention affects rehabilitation outcomes. This retrospective, observational, single-center, cohort study included consecutive geriatric patients (n = 448) with pharmacist-led intervention between 2017 and 2019. Participants were divided based on pharmacist-led deprescribing and non deprescribing interventions during hospitalization. Demographic data, laboratory data, the Functional Independence Measure were (FIM) analyzed between the groups. Multiple linear regression analysis was performed to analyze the relationship between pharmacist-led deprescribing and FIM total gain. The primary outcome was FIM total gain. The rate of pharmacist intervention during the study period was 92.4%. A multiple linear regression analysis of FMI-T gain, adjusting for confounding factors, revealed that the pharmacist-led deprescribing intervention was independently correlated with FMI-T gain. Particularly, the use of dyslipidemia drugs, antipsychotic drugs, hypnotics, and nonsteroidal anti-inflammatory drugs significantly decreased during hospitalization. The pharmacist-led deprescribing intervention was independently and significantly associated with FIM-T gain. The pharmacist-led deprescribing intervention improved functional recovery in a rehabilitation setting.

Outcomes of robot-assisted versus conventional laparoscopic low anterior resection in patients with rectal cancer: propensity-matched analysis of the National Clinical Database in Japan.

BACKGROUND: Robot-assisted laparoscopic surgery has several advantages over conventional laparoscopy. However, population-based comparative studies for low anterior resection are limited. This article aimed to compare peri-operative results of robot-assisted low anterior resection (RALAR) and laparoscopy. METHODS: This retrospective cohort study used data from patients treated with RALAR or conventional laparoscopic low anterior resection (CLLAR) between October 2018 and December 2019, as recorded in the Japanese National Clinical Database, a data set registering clinical information, perioperative outcomes, and mortality. Of note, the registry does not include information on the tumour location (centimetres from the anal verge) and diverting stoma creation. Perioperative outcomes, including rate of conversion to open surgery, were compared between RALAR and CLLAR groups. Confounding factors were adjusted for using propensity score matching. RESULTS: Of 21 415 patients treated during the study interval, 20 220 were reviewed. Two homogeneous groups of 2843 patients were created by propensity score matching. The conversion rate to open surgery was significantly lower in the RALAR group than in the CLLAR group (0.7 versus 2.0 per cent; P < 0.001). The RALAR group had a longer operating time (median: 352 versus 283 min; P < 0.001), less intraoperative blood loss (15 versus 20 ml; P < 0.001), a lower in-hospital mortality rate (0.1 versus 0.5 per cent; P = 0.007), and a shorter postoperative hospital stay (median: 13 versus 14 days; P < 0.001) compared with the CLLAR group. The CLLAR group had a lower rate of readmission within 30 days (2.4 versus 3.3 per cent; P = 0.045). CONCLUSION: These data highlight the reduced conversion rate, in-hospital mortality rate, intraoperative blood loss, and length of postoperative hospital stay for rectal cancer surgery in patients treated using robot-assisted laparoscopic surgery compared with laparoscopic low anterior resection.

Long-term clinical impact of serum albumin in coronary artery disease patients with preserved renal function.

BACKGROUND AND AIMS: Low serum albumin level is reportedly associated with worse clinical outcomes in patients with chronic kidney disease (CKD). However, associations between decreased serum albumin level and outcomes in non-CKD patients with coronary artery disease (CAD) remain unclear. Therefore, we aimed to evaluate the prognostic value of serum albumin concentrations in stable CAD patients with preserved renal function. METHODS AND RESULTS: We studied 1316 patients with CAD and preserved renal function (estimated glomerular filtration rate ≥60 mL/min/1.73 m2) who underwent their first PCI between 2000 and 2011 and had data available for pre-procedural serum albumin. Patients were assigned to quartiles based on pre-procedural albumin concentrations. The incidence of major adverse cardiac events (MACE), including all-cause death and non-fatal myocardial infarction, was evaluated. Mean albumin concentration was 4.1 ± 0.4 g/dL. During the median follow-up of 7.5 years, 181 events occurred (13.8%). Kaplan-Meier curves revealed that patients with decreased serum albumin concentrations showed a higher event rate for MACE (log-rank, p < 0.0001). Using the highest tertiles (>4.3 g/dL) as reference, adjusted hazard ratios were 1.97 (95% CI, 1.12-3.55), 1.77 (95% CI, 0.99-3.25), and 1.19 (95% CI, 0.68-2.15) for serum albumin concentrations of <3.9, 3.9-4.0, and 4.1-4.3 g/dL, respectively. Decreased serum albumin concentration was associated with MACE even after adjusting for other independent variables (HR, 2.21 per 1-g/dL decrease; 95% CI, 1.37-3.56, p = 0.001). CONCLUSION: Decreased serum albumin concentration independently predicted worse long-term prognosis in non-CKD patients after PCI. Pre-procedural serum albumin concentration could offer a useful predictor for patients with CAD and preserved renal function.

Evaluation of swallowing ability using swallowing sounds in maxillectomy patients.

Maxillectomy for oral tumours often results in debilitating oral hypofunction, which markedly decreases quality of life. Dysphagia, in particular, is one of the most serious problems following maxillectomy. This study used swallowing sounds as a simple evaluation method to evaluate swallowing ability in maxillectomy patients with and without their obturator prosthesis placed. Twenty-seven maxillectomy patients (15 men, 12 women; mean age 66.0 ± 12.1 years) and 30 healthy controls (14 men, 16 women; mean age 44.9 ± 21.3 years) were recruited for this study. Participants were asked to swallow 4 mL of water, and swallowing sounds were recorded using a throat microphone. Duration of the acoustic signal and duration of peak intensity (DPI) were measured. Duration of peak intensity was significantly longer in maxillectomy patients without their obturator than with it (P < .05) and was significantly longer in maxillectomy patients without their obturator than in healthy controls (P < .025 after Bonferroni correction). With the obturator placed, DPI was significantly longer in maxillectomy patients who had undergone soft palate resection than in those who had not (P < .05). These results suggest swallowing ability in maxillectomy patients could be improved by wearing an obturator prosthesis, particularly during the oral stage. However, it is difficult to improve the oral stage of swallowing in patients who have undergone soft palate resection even with obturator placement.

Polymerization Behavior and Mechanical Properties of High-Viscosity Bulk Fill and Low Shrinkage Resin Composites.

The present study determined the mechanical properties and volumetric polymerization shrinkage of different categories of resin composite. Three high viscosity bulk fill resin composites were tested: Tetric EvoCeram Bulk Fill (TB, Ivoclar Vivadent), Filtek Bulk Fill posterior restorative (FB, 3M ESPE), and Sonic Fill (SF, Kerr Corp). Two low-shrinkage resin composites, Kalore (KL, GC Corp) and Filtek LS Posterior (LS, 3M ESPE), were used. Three conventional resin composites, Herculite Ultra (HU, Kerr Corp), Estelite ∑ Quick (EQ, Tokuyama Dental), and Filtek Supreme Ultra (SU, 3M ESPE), were used as comparison materials. Following ISO Specification 4049, six specimens for each resin composite were used to determine flexural strength, elastic modulus, and resilience. Volumetric polymerization shrinkage was determined using a water-filled dilatometer. Data were evaluated using analysis of variance followed by Tukey's honestly significant difference test (α=0.05). The flexural strength of the resin composites ranged from 115.4 to 148.1 MPa, the elastic modulus ranged from 5.6 to 13.4 GPa, and the resilience ranged from 0.70 to 1.0 MJ/m3. There were significant differences in flexural properties between the materials but no clear outliers. Volumetric changes as a function of time over a duration of 180 seconds depended on the type of resin composite. However, for all the resin composites, apart from LS, volumetric shrinkage began soon after the start of light irradiation, and a rapid decrease in volume during light irradiation followed by a slower decrease was observed. The low shrinkage resin composites KL and LS showed significantly lower volumetric shrinkage than the other tested materials at the measuring point of 180 seconds. In contrast, the three bulk fill resin composites showed higher volumetric change than the other resin composites. The findings from this study provide clinicians with valuable information regarding the mechanical properties and polymerization kinetics of these categories of current resin composite.

Effect of interlamellar interactions on shear induced multilamellar vesicle formation.

Shear-induced multilamellar vesicle (MLV) formation has been studied by coupling the small-angle neutron scattering (SANS) technique with neutron spin echo (NSE) spectroscopy. A 10% mass fraction of the nonionic surfactant pentaethylene glycol dodecyl ether (C12E5) in water was selected as a model system for studying weak inter-lamellar interactions. These interactions are controlled either by adding an anionic surfactant, sodium dodecyl sulfate, or an antagonistic salt, rubidium tetraphenylborate. Increasing the charge density in the bilayer induces an enhanced ordering of the lamellar structure. The charge density dependence of the membrane bending modulus was determined by NSE and showed an increasing trend with charge. This behavior is well explained by a classical theoretical model. By considering the Caillé parameters calculated from the SANS data, the layer compressibility modulus B¯ is estimated and the nature of the dominant inter-lamellar interaction is determined. Shear flow induces MLV formation around a shear rate of 10 s-1, when a small amount of charge is included in the membrane. The flow-induced layer undulations are in-phase between neighboring layers when the inter-lamellar interaction is sufficiently strong. Under these conditions, MLV formation can occur without significantly changing the inter-lamellar spacing. On the other hand, in the case of weak inter-lamellar interactions, the flow-induced undulations are not in-phase, and greater steric repulsion leads to an increase in the inter-lamellar spacing with shear rate. In this case, MLV formation occurs as the amplitude of the undulations gets larger and the steric interaction leads to in-phase undulations between neighboring membranes.

Geographical variation in the skeletal morphology of red jungle fowl.

1. The skulls and postcranial skeletons of the red jungle fowl (Gallus gallus) were compared osteometrically between the populations from North and South Vietnam, North and Central Laos and Southeast Bangladesh. The populations include the three subspecies of G. g. spadiceus, G. g. gallus and G. g. murghi and were sampled to reveal the geographical morphological variations among populations in G. gallus. 2. The morphometric characteristics of subspecies murghi could be clearly distinguished from those of the other subspecies using a canonical discriminant analysis. However, the size and shape of the skull of the gallus population from South Vietnam were not statistically different from that of the subspecies spadiceus from North Laos. The canonical discriminant scores also clearly indicated that there were morphological similarities in the skulls of the populations from North Laos and South Vietnam. 3. From the results, therefore, it is concluded that red jungle fowls do not exhibit high levels of osteometric variation between geographical localities at least within the Indochinese Peninsula. 4. This contrasts with previous studies which have described these subspecies as having various external morphological differences and have argued that zoogeographical barriers exist between the north and south areas of the Indochinese Peninsula.

C-type lectin-like receptor 2 promotes hematogenous tumor metastasis and prothrombotic state in tumor-bearing mice.

Essentials The role of C-type lectin-like receptor-2 (CLEC-2) in cancer progression is unclear. CLEC-2-depleted mouse model is generated by using a rat anti-mouse CLEC-2 monoclonal antibody. CLEC-2 depletion inhibits hematogenous tumor metastasis of podoplanin-expressing B16F10 cells. CLEC-2 depletion prolongs cancer survival by suppressing thrombosis and inflammation. SUMMARY: Background C-type lectin-like receptor 2 (CLEC-2) is a platelet activation receptor of sialoglycoprotein podoplanin, which is expressed on the surface of certain types of tumor cells. CLEC-2-podoplanin interactions facilitate hematogenous tumor metastasis. However, direct evidence of the role of CLEC-2 in hematogenous metastasis and cancer progression is lacking. Objective and methods We generated immunological CLEC-2-depleted mice by using anti-mouse CLEC-2 monoclonal antibody 2A2B10 and investigated whether CLEC-2 promoted hematogenous tumor metastasis and tumor growth and exacerbated the prognosis of mice bearing podoplanin-expressing B16F10 melanoma cells. Results Our results showed that hematogenous metastasis was significantly inhibited in CLEC-2-depleted mice. B16F10 cells co-cultured with wild-type platelets, but not with CLEC-2-deficient platelets, showed increased proliferation. However, B16F10 cell proliferation was not inhibited in CLEC-2-depleted mice. Histological analysis showed that thrombus formation in tumor vessels was significantly inhibited and functional vessel density was significantly increased in CLEC-2-depleted mice. These data suggest that CLEC-2 deficiency may inhibit thrombus formation in tumor vessels and increase the density of functional vessels, thus improving oxygen and nutrient supply to tumors, indirectly promoting tumor proliferation. Furthermore, the overall survival of CLEC-2-depleted mice was significantly prolonged, which may be due to the suppression of thrombus formation in the lungs and subsequent inhibition of systemic inflammation and cachexia. Conclusions These data provide a rationale for the targeted inhibition of CLEC-2 as a new strategy for preventing hematogenous tumor metastasis and for inhibiting cancer-related thromboembolism.

Inelastic and quasi-elastic neutron scattering spectrometers in J-PARC.

J-PARC, Japan Proton Accelerator Research Complex provides short pulse proton beam at a repetition rate 25Hz and the maximum power is expected to be 1MW. Materials and Life Science Experimental Facility (MLF) has 23 neutron beam ports and 21 instruments have already been operated or under construction/commissioning. There are 6 inelastic/quasi-elastic neutron scattering spectrometers and the complementary use of these spectrometers will open new insight for life science. This article is part of a Special Issue entitled "Science for Life" Guest Editor: Dr. Austen Angell, Dr. Salvatore Magazù and Dr. Federica Migliardo.

The induction of MIG6 under hypoxic conditions is critical for dormancy in primary cultured lung cancer cells with activating EGFR mutations.

The biologic activity of individual cancer cells is highly heterogeneous. Hypoxia, one of the prominent features of a tumor microenvironment, is thought to be causal in generating this cellular heterogeneity. In this study, we revealed that primary lung cancer cells harboring activating epidermal growth factor receptor (EGFR) mutations generally entered a dormant state when hypoxic. We found that heterodimer formation of the ERBB family receptor tyrosine kinases (RTKs), and their subsequent downstream signaling, was diminished under hypoxic conditions, although phosphorylation of the EGFR was retained. Dormant lung cancer cells were found to be resistant to EGFR tyrosine kinase inhibitor (TKI) treatment. In terms of mechanism, we found that a negative regulator of ERBB signaling, MIG6/ERRFI1/RALT/Gene33, was induced by hypoxia both in vitro and in vivo. MIG6 expression prevented heterodimer formation of ERBB family RTKs, and suppressed their downstream signaling. Knockdown of MIG6 enhanced tumor cell growth under hypoxic conditions, and promoted the phosphorylation of ERK and AKT via increased EGFR-HER3 binding. Critically, sensitivity to an EGFR-TKI, as well as to irradiation under hypoxic conditions, was increased in MIG6 knockdown cells. The expression of MIG6 was partly correlated with a pS6 negative zone in patient tumors. Analyses of tumor sections from 68 patients with activating EGFR mutations showed that patients with high MIG6 expression showed significantly shorter survival after EGFR-TKI treatment than other groups. Collectively, our data suggest that dormant cancer cells with a high MIG6 expression level might be one of the causes of EGFR-TKI resistance in EGFR mutant lung cancer cells.

Influence of Etching Mode on Enamel Bond Durability of Universal Adhesive Systems.

The purpose of this study was to determine the enamel bond durability of three universal adhesives in different etching modes through fatigue testing. The three universal adhesives used were Scotchbond Universal, Prime&Bond Elect universal dental adhesive, and All-Bond Universal light-cured dental adhesive. A single-step self-etch adhesive, Clearfil S3 Bond Plus was used as a control. The shear bond strength (SBS) and shear fatigue strength (SFS) to human enamel were evaluated in total-etch mode and self-etch mode. A stainless steel metal ring with an internal diameter of 2.4 mm was used to bond the resin composite to the flat-ground (4000-grit) tooth surfaces for determination of both SBS and SFS. For each enamel surface treatment, 15 specimens were prepared for SBS and 30 specimens for SFS. The staircase method for fatigue testing was then used to determine the SFS of the resin composite bonded to the enamel using 10-Hz frequencies for 50,000 cycles or until failure occurred. Scanning electron microscopy was used to observe representative debonded specimen surfaces and the resin-enamel interfaces. A two-way analysis of variance and the Tukey post hoc test were used for analysis of the SBS data, whereas a modified t-test with Bonferroni correction was used for the SFS data. All adhesives in total-etch mode showed significantly higher SBS and SFS values than those in self-etch mode. Although All-Bond Universal in self-etch mode showed a significantly lower SBS value than the other adhesives, there was no significant difference in SFS values among the adhesives in this mode. All adhesives showed higher SFS:SBS ratios in total-etch mode than in self-etch mode. With regard to the adhesive systems used in this study, universal adhesives showed higher enamel bond strengths in total-etch mode. Although the influence of different etching modes on the enamel-bonding performance of universal adhesives was found to be dependent on the adhesive material, total-etch mode effectively increased the enamel bond strength and durability, as measured by fatigue testing.

Quantitative Assessment of Circumferential Enhancement along the Wall of Cerebral Aneurysms Using MR Imaging.

BACKGROUND AND PURPOSE: The incidence of wall enhancement of cerebral aneurysms on vessel wall MR imaging has been described as higher in ruptured intracranial aneurysms than in unruptured intracranial aneurysms, but the difference in the degree of enhancement between ruptured and unruptured aneurysms is unknown. We compared the degree of enhancement between ruptured and unruptured intracranial aneurysms by using quantitative MR imaging measures. MATERIALS AND METHODS: We performed quantitative analyses of circumferential enhancement along the wall of cerebral aneurysms in 28 ruptured and 76 unruptured consecutive cases by using vessel wall MR imaging. A 3D-T1-weighted fast spin-echo sequence was obtained before and after contrast media injection, and the wall enhancement index was calculated. We then compared characteristics between ruptured and unruptured aneurysms. RESULTS: The wall enhancement index was significantly higher in ruptured than in unruptured aneurysms (1.70 ± 1.06 versus 0.89 ± 0.88, respectively; P = .0001). The receiver operating characteristic curve analysis found that the most reliable cutoff value of the wall enhancement index to differentiate ruptured from unruptured aneurysms was 0.53 (sensitivity, 0.96; specificity, 0.47). The wall enhancement index remained significant in the multivariate logistic regression analysis (P < .0001). CONCLUSIONS: Greater circumferential enhancement along the wall of cerebral aneurysms correlates with the ruptured state. A quantitative evaluation of circumferential enhancement by using vessel wall MR imaging could be useful in differentiating ruptured from unruptured intracranial aneurysms.

Porosity dependency of an optimized stent design for an intracranial aneurysm.

BACKGROUND: Optimal design of stents for a cerebral aneurysm is desired for efficient flow reduction in the aneurysm. OBJECTIVE: In this study, we aimed to optimize stent design at several porosities, estimate the influence of stent design on aneurysm flow, and evaluate the ability of stents to reduce flow. METHODS: Stent models were constructed as sets of squares or rectangles in the necks of a two-dimensional (2D) and realistic aneurysm. Then, automated optimization was performed using a combination of simulated annealing and lattice Boltzmann flow simulation. RESULTS: By simulated annealing, stents were gradually modified to reduce the average velocity in an aneurysm. As a result of optimization, stents of all porosities demonstrated an inhomogeneous distribution with dense struts in the inflow area. Flow reduction was increased compared with the initial stent. Under the condition of high porosity, flow reduction by the stent drastically increased as porosity decreased. Under low porosity, the increase of velocity reduction was moderate even as porosity decreased. CONCLUSIONS: Optimization can enhance flow reduction by stents. However, the increase in reduction associated with decreasing porosity is moderate under lower-porosity conditions. This threshold may help in the choice of stent porosity for each specific aneurysm.

Subclavian artery intervention with a balloon-tipped occlusion catheter via the ipsilateral brachial artery without an introducer sheath.

To protect against a distal embolism in the vertebral artery, subclavian artery stenting can be achieved by positioning a filter device or balloon in the ipsilateral vertebral artery. However, treatment with these devices is not easy, and it is also an inaccurate method for cerebral protection. We developed a balloon-tipped occlusion catheter (Optimo(®) occlusion catheter) without an introducer sheath, which allowed us to perform the minimally invasive endovascular therapy (EVT). Herein, we report two EVT cases for subclavian artery disease treated with an Optimo(®) occlusion catheter via the ipsilateral brachial artery. This method is effective for distal protection of both cerebral and brachial artery embolism, and also enables EVT procedure retrogradely as well.

Ibuprofen enhances the anticancer activity of cisplatin in lung cancer cells by inhibiting the heat shock protein 70.

Hsp70 is often overexpressed in cancer cells, and the selective cellular survival advantage that it confers may contribute to the process of tumour formation. Thus, the pharmacological manipulation of Hsp70 levels in cancer cells may be an effective means of preventing the progression of tumours. We found that the downregulation of Hsp70 by ibuprofen in vitro enhances the antitumoural activity of cisplatin in lung cancer. Ibuprofen prominently suppressed the expression of Hsp70 in A549 cells derived from lung adenocarcinoma and sensitized them to cisplatin in association with an increase in the mitochondrial apoptotic cascade, whereas ibuprofen alone did not induce cell death. The cisplatin-dependent events occurring up- and downstream of mitochondrial disruption were accelerated by treatment with ibuprofen. The increase in cisplatin-induced apoptosis caused by the depletion of Hsp70 by RNA interference is evidence that the increased apoptosis by ibuprofen is mediated by its effect on Hsp70. Our observations indicate that the suppression of Hsp70 by ibuprofen mediates the sensitivity to cisplatin by enhancing apoptosis at several stages of the mitochondrial cascade. Ibuprofen, therefore, is a potential therapeutic agent that might allow lowering the doses of cisplatin and limiting the many challenge associated with its toxicity and development of drug resistance.

Functional morphology of the aardvark tail.

The musculoskeletal system of the aardvark (Orycteropus afer) tail was morphologically examined in two adult specimens. The tail musculature comprised three muscular groups, viz. a dorsal sacrocaudal system that consisted of the irregularly oriented Musculus sacrocaudalis dorsalis medialis and M. sacrocaudalis dorsalis lateralis, a lateral inter-vertebral connecting system, and a ventral sacrocaudal system characterized by the thick M. sacrocaudalis ventralis lateralis and M. sacrocaudalis ventralis medialis. Both the dorsal and ventral systems possessed large tendon groups that strengthened the tail structure. Computed tomography (CT) examination showed the presence of large but homogeneous cartilaginous inter-vertebral discs, whereas V-shaped bones were situated at the ventral aspect of the caudal vertebrae at the level of the inter-vertebral discs. CT visualization of the tendons and V-shaped bones in various tail positions suggested that these structures contribute to the tunnel digging action by bearing the trunk weight and lending force when the aardvark are displacing the soil by means of the forelimbs.