A guide to classify tattoo motives in Mexico as a tool to identify unknown bodies.
In Mexico, the number of unidentified bodies has been steadily rising for years. By now, more than 50,000 bodies are considered unidentified. Forensic laboratories that could perform comparative molecular genetic investigation are often overburdened and examinations can take months. Therefore, pragmatic approaches that can help to identify more unknown bodies must be sought. The increased use of distinctive physical features might be one, and the high rate of tattooed people in Mexico points towards a great potential of tattoos as a tool for identification. The prerequisite for a comparison of antemortem (missing persons) and postmortem (unknown bodies) data is an objective description of the particularities, e.g., of the tattoos. The aim of this study was to establish an objective classification for tattoo motives, taking into consideration local preferences. In the database of the medicolegal services of the Instituto Jaliscience de Ciencias Forenses (IJCF) in Guadalajara, postmortem data of 1000 tattooed bodies from 2019 were evaluated. According to sex and age, the tattooed body localization and the tattoo motives were categorized. The 1000 tattooed deceased showed tattoos on 2342 body localizations. The motives were grouped and linked to the following 11 keywords (with decreasing frequency): letters/numbers, human, symbol (other), plant, symbol (religious), animal, object, fantasy/demon/comic, tribal/ornament/geometry, other, unrecognizable. Using the proposed classification, tattoo motives can be described objectively and classified in a practical way. If used for antemortem (missing persons) and postmortem (unknown bodies) documentation, motives can be searched and compared efficiently-helping to identify unknown bodies.


SI-27, a novel inhibitor of matrix metalloproteinases with antiangiogenic activity: detection with a variable-pressure scanning electron microscope.
Degradation of basement membrane is one the of crucial steps in tumor angiogenesis and is performed by matrix metalloproteinases (MMPs). This study was designed to investigate the suppression of tumor angiogenesis by SI-27, an MMP inhibitor. SI-27 was applied at noncytotoxic concentrations (1-100 micromol/L), and its effect on nonmitogenic vascular endothelial growth factor (VEGF)-enhanced cell motility and in vitro angiogenesis by human umbilical vein endothelial cells was determined. The activity of MMP-1, MMP-2, and tissue inhibitor of metalloproteinase 1 was determined by enzyme-linked immunosorbent assay. The effect of SI-27 on in vitro angiogenesis stimulated by supernatants of human glioma cell lines (U87MG, U251MG, and U373MG) also was examined. Angiogenesis was detected with variable vacuum scanning electron microscopy. Cell motility and in vitro angiogenesis by human umbilical vein endothelial cells were significantly increased by VEGF. The maximal effect on cell motility by VEGF was noted at 5 ng/ml (P < 0.001), and the maximal effect on the capillary network was observed at 10 ng/ml (P < 0.001), along with elevated MMP-1 and MMP-2 activity. Whereas SI-27 significantly suppressed VEGF-mediated in vitro angiogenesis (50 micromol/L; P < 0.001) and inactivated both MMP-1 and MMP-2, the expression of tissue inhibitor of metalloproteinase 1 and VEGF-mediated cell motility were not affected by SI-27. The angiogenesis promoted by glioma supernatants showed a significant reduction in the presence of SI-27 (10 micromol/L; U87MG, P < 0.01; U251MG, P < 0.01; U373MG, P < 0.01). SI-27 inhibited in vitro tumor angiogenesis by suppression of MMP. This agent may be anticipated to prevent tumor growth through an angiosuppressive effect.


Nintedanib Ameliorates Bleomycin-Induced Pulmonary Fibrosis, Inflammation, Apoptosis, and Oxidative Stress by Modulating PI3K/Akt/mTOR Pathway in Mice.
Idiopathic pulmonary fibrosis (IPF) seriously threatens human life and health, and no curative therapy is available at present. Nintedanib is the first agent approved by the US Food and Drug Administration (FDA) in order to treat IPF; however, its mechanism of inhibition of IPF is still elusive. According to recent studies, nintedanib is a potent inhibitor. It can antagonize platelet-derived growth factor (PDGF), basic fibroblast growth factor (b-FGF), vascular endothelial growth factor (VEGF), etc., to inhibit pulmonary fibrosis. Whether there are other signaling pathways involved in IPF remains unknown. This study focused on investigating the therapeutic efficacy of nintedanib in bleomycin-mediated pulmonary fibrosis (PF) mice through PI3K/Akt/mTOR pathway. Following the induction of pulmonary fibrosis in C57 mice through bleomycin (BLM) administration, the mice were randomized into five groups: (1) the normal control group, (2) the BLM model control group, (3) the low-dose Nintedanib administration model group, (4) the medium-dose nintedanib administration model group, and (5) the high-dose nintedanib administration model group. For lung tissues, morphological changes were found by HE staining and Masson staining, ELISA method was used to detect inflammatory factors, alkaline water method to estimate collagen content, and western blotting for protein levels. TUNEL staining and immunofluorescence methods were used to analyze the effect of nintedanib on lung tissue and the impacts and underlying mechanisms of bleomycin-induced pulmonary fibrosis. After 28 days, bleomycin-treated mice developed significant pulmonary fibrosis. Relative to bleomycin-treated mice, nintedanib-treated mice had markedly reduced degrees of PF. In addition, nintedanib showed lung-protective effects by up-regulating antioxidant levels, down-regulating inflammatory protein expression, and reducing collagen accumulation. We demonstrated that nintedanib ameliorated bleomycin-induced lung injury by inhibiting the P13K/Akt/mTOR pathway as well as apoptosis. In addition, significant improvement in pulmonary fibrosis was seen after nintedanib (30/60/120 mg/kg body weight/day) treatment through a dose-dependent way. Histopathological results further corroborated the effect of nintedanib treatment on remarkably attenuating bleomycin-mediated mouse lung injury. According to our findings, nintedanib restores the antioxidant system, suppresses pro-inflammatory factors, and inhibits apoptosis. Nintedanib can reduce bleomycin-induced inflammation by downregulating PI3K/Akt/mTOR pathway, PF, and oxidative stress (OS).


Reiki training for caregivers of hospitalized pediatric patients: a pilot program.
To explore the feasibility of a Reiki therapy-training program for the caregivers of pediatric medical or oncology inpatients, at a large pediatric hospital, a series of Reiki training classes were offered by a Reiki Master. At completion of the training, an interview was conducted to elicit participant's feedback regarding the effectiveness and feasibility of the training program. Seventeen of the 18 families agreed to participate. Most families (65%) attended three Reiki training sessions, reporting that Reiki benefitted their child by improving their comfort (76%), providing relaxation (88%), and pain relief (41%). All caregivers identified becoming an active participant in their child's care as a major gain from participation in the Reiki training. A hospital-based Reiki training program for caregivers of hospitalized pediatric patients is feasible and can positively impact patients and their families. More rigorous research regarding the benefits of Reiki in the pediatric population is needed.


Oroxylin A inhibits matrix metalloproteinase-2/9 expression and activation by up-regulating tissue inhibitor of metalloproteinase-2 and suppressing the ERK1/2 signaling pathway.
Matrix metalloproteinases (MMPs) play important roles in the invasion and migration of cancer cells. In this study, we used in vitro and in vivo assays to examine the inhibitory effects of oroxylin A, one of the main bioactive flavonoid extracted from Scutellaria radix, on the human breast carcinoma cell MDA-MB-231 invasion and migration. We found that oroxylin A can suppress cell adhesion, invasion and migration in a concentration-dependent manner. Moreover, oroxylin A led to the reduction of the activity and expression levels of MMP-2 and MMP-9 in gelatin zymography, real-time PCR and western blotting analysis. Further elucidation of the mechanism revealed that oroxylin A increased the expression of tissue inhibitor of metalloproteinase-2 (TIMP-2), the endogenous inhibitor of MMP-2, and repressed the phorbol-12-myristate-13-acetate (PMA)-induced translocation of protein kinase Cδ (PKCδ), phosphorylation of extracellular signal-regulated kinase (ERK1/2) and binding activity of the transcription factor activator protein-1 (AP-1) which are upstream signaling molecules in MMP-9 expression. Our results also indicated that oroxylin A inhibited the lung metastasis of murine melanoma cell B16-F10 in vivo. Therefore, we proposed that oroxylin A might be developed as a therapeutic potential candidate for the treatment of cancer metastasis.


Two cases of pott disease associated with bilateral psoas abscesses: case report.
Two case reports and a literature review of spinal osteomyelitis with bilateral psoas abscesses secondary to Mycobacterium tuberculosis. Describe the presentation, diagnosis, treatment, and outcome of spinal tuberculosis (i.e., Pott disease). Pott disease is a well-known condition in unindustrialized countries causing multiple spinal deformities in children. However, its association with bilateral psoas abscesses in adults with minimal risk factors is not commonly recognized in industrialized countries. There are 2 adult cases of Pott disease with psoas abscesses presented, and the relevant literature is reviewed. Plain spine radiographs, spine magnetic resonance imaging (MRI), routine bacterial and acid-fast bacilli cultures of infected material, and other diagnostic testing for M. tuberculosis were performed. Plain radiographs and MRI of the spine showed vertebral osteomyelitis with compression fractures, and MRI also revealed bilateral psoas abscesses. Acid-fast bacilli culture and other M. tuberculosis diagnostic testing of psoas abscess specimens confirmed the diagnosis of M. tuberculosis. Although spinal osteomyelitis with psoas abscess is classically associated with Staphylococcus aureus infection, Pott disease should be considered in this clinical setting, and risk factor assessment and testing for tuberculosis should be performed.


Vasculitis and glomerulonephritis: a subgroup with an antineutrophil cytoplasmic antibody.
Four subjects whose plasma produced positive staining of neutrophil cytoplasm, on testing for antinuclear factor, have been found over eight years (and over 10,000 antinuclear factor studies). All four had evidence of diffuse systemic disease with polyarthralgia and lung involvement. Three of four (at least) had evidence of renal involvement and two of four skin biopsy evidence of vasculitis. Defining such a subgroup may help in defining etiology(s) and treatment regimes in diffuse vasculitic disease.


Involvement of fast synaptic inhibition in the generation of high-frequency oscillation in central respiratory system.
During moderate hypercapnia, spectrum analysis of efferent phrenic nerve activity (PNA) of urethane anesthetized rabbits revealed high-frequency oscillations (HFO). The spectral peak (mean frequency 111 Hz) was reversibly eliminated by the glycine receptor antagonist strychnine administered into the 4th cerebral ventricle. In contrast, blockade of brainstem GABAA receptors by bicuculline did not abolish HFO but even reinforced or induced HFO. Thus, there is evidence that fast synaptic inhibition via glycine receptors is involved in the generation of HFO within the medullary respiratory center, whereas GABA may play a modulatory role.


Thyroid hemiagenesis and Hashimoto's thyroditis-diagnostic and treatment pitfalls.
Thyroid hemiagenesis (TH) is a rare congenital disease with absence of a thyroid lobe; most patients have no clinical symptoms. The etiology of TH remains unclear. In this paper, we describe a rare case of TH and congenital absence of the ipsilateral parathyroid gland, found during the operation, combined with the autoimmune disease Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis. A 31-year-old woman was admitted to our hospital because of a mass in the right neck. Surgical exploration validated the absence of the left lobe of the thyroid and parathyroid glands, and pathological examination of the excised nodules confirmed Hashimoto's thyroiditis. Patients with TH might show accompanying absence of the ipsilateral parathyroid gland. The case described here, in which TH was combined with Hashimoto's thyroiditis, is rare in the medical literature. The operation should be ended at once if Hashimoto's thyroiditis is diagnosed during surgery. Absence of thyroid lobe may accompany with a congenital absence of the ipsilateral parathyroid gland and Hashimoto's thyroiditis. Fine needle aspiration is essential to diagnosis and decision-making of the treatment.


1-(2-Naphthyl)-1H-pyrazole-5-carboxylamides as potent factor Xa inhibitors. Part 3: Design, synthesis and SAR of orally bioavailable benzamidine-P4 inhibitors.
Using N,N-dialkylated benzamidines as the novel P4 motifs, we have designed and synthesized a class of 1-(2-naphthyl)-1H-pyrazole-5-carboxylamides as highly potent and selective fXa inhibitors with significantly improved hydrophilicity and in vitro anticoagulant activity. These benzamidine-P4 fXa inhibitors have displayed excellent oral bioavailability and long half-life.


Fast drug stability determination by LC variable-parameter kinetic experiments.
Variable-parameter kinetic experiments were carried out using HPLC as analytical instrument. The hydrolysis of aspirin was followed both at variable-temperature and at variable-pH conditions. The peak areas relative to salicylic acid were processed by direct fit to a mathematical model and/or by differential method obtaining, by single experiments, the values of the apparent rate constant in the whole range of temperature and pH studied. The results, although the discontinuity of this kind of analysis, are in agreement with those obtained by constant-parameter kinetics but saving experimental time.


Sch 37137, a novel antifungal compound produced by a Micromonospora sp. Taxonomy, fermentation, isolation, structure and biological properties.
A new antifungal compound, Sch 37137, was isolated from the cultured broth of a Micromonospora sp., SCC 1792. Sch 37137 is structurally related to A 19009, a dipeptide previously discovered from a Streptomyces sp. The compound was weakly active against species of Candida and dermatophytes (mean MICs greater than or equal to 128 micrograms/ml) in Sabouraud dextrose, yeast-nitrogen and modified Eagles minimum essential media; however activity against Candida sp. (mean MICs greater than or equal to 12 micrograms/ml) and dermatophytes (mean MICs greater than or equal to 0.8 microgram/ml) significantly improved in MA medium.


Effect of chronic ethanol exposure on the hepatotoxicity of ecstasy in mice: an ex vivo study.
3,4-Methylenedioxymethamphetamine (MDMA) is frequently consumed at "rave" parties by polydrug users that usually take this drug in association with ethanol. In addition, many young people are repeatedly exposed to ethanol, which likely leads to tolerance phenomena. Both compounds are metabolized in the liver, with formation of hepatotoxic metabolites, which gives high relevance to the evaluation of their putative toxicological interaction. Therefore, the aim of this study was to evaluate the toxicity induced by 0.8 and 1.6 mM MDMA to freshly isolated hepatocytes obtained from ethanol-treated mice whose tap drinking water was replaced by a 5% ethanol solution for 1 week and, afterwards, by a 12% ethanol solution for 8 weeks (ethanol group) comparatively to non-treated animals (non-ethanol group). The hepatocytes were incubated under normothermic and hyperthermic conditions in order to simulate in vitro the hyperthermic response induced in vivo by MDMA, a condition that has been recognized as a life-threatening effect associated with MDMA exposure and implicated in its hepatotoxicity. Six mice treated under the same protocol as the ethanol group were used for histological analysis, and compared to non-ethanol-treated animals. The pre-treatment of mice with ethanol caused a significant decrease in the hepatocytes yield in the isolation procedure comparatively to the non-ethanol group, which can be explained by an increase in collagen deposition along the hepatic parenchyma as observed in the histological analysis. The initial cell viability of hepatocytes suspensions was similar between ethanol and non-ethanol groups. However, the ethanol group showed a higher GSH oxidation rate, which was enhanced under hyperthermia. Additionally, a concentration-dependent MDMA-induced loss of cell viability and ATP depletion was observed for both groups, at 41 degrees C. In conclusion, the repeated treatment with ethanol seems to increase the vulnerability of freshly isolated mice hepatocytes towards pro-oxidant conditions, as ascertained by the increase in collagen deposition, lower hepatocyte yield and decreased glutathione levels. However, MDMA toxicity to the isolated hepatocytes was independent of ethanol pre-treatment, while significantly dependent on incubation temperature.


Formation of alternative proteasomes: same lady, different cap?
The 26S proteasome is thought to be a homogenous complex, consisting of a 20S proteolytic core and a 19S regulatory particle that is required for its activation. Two groups have recently reported the activation of archeal 20S by a p97-related double-ring AAA+ ATPase complex, in a similar fashion to that reported for 19S. Since p97 is found in eukaryotes, the existence of a parallel setting in higher organisms is intriguing. Herein, we present supporting data and hypothesize that in eukaryotes, p97 and CSN form a promiscuous, hence hard-to-detect, "alternative cap", enabling the prompt and precise elimination of particular substrates.


Long-term effects of two organic amendments on bacterial communities of calcareous mediterranean soils degraded by mining.
The application of organic amendments to improve the chemical and biological properties of degraded soils from calcareous quarries is necessary to accelerate restoration processes. The aim of this study is to assess the success of different restoration treatments in the long-term using two organic amendments (sewage sludge from urban waste water (SS) and compost from domestic solid waste (CW)). The chemical properties and bacterial communities of restored soils were compared with unamended soils (NA) and surrounding natural soils (NS) from a limestone quarry in a semi-arid ecosystem. After 10 years of the addition of organic amendments, the abundance of soil bacteria, diversity, and taxonomic composition at the phylum and genus level in each soil type was analysed by rRNA 16 S amplification (PCR), sequencing using Illumina, and comparison with the SILVA database using QIIME2 software. The relationships between soil bacterial taxa and chemical soil properties (pH, electrical conductivity (EC), total organic carbon (TOC), and total nitrogen content (TN)) were also studied, as well as the interrelations between soil bacterial taxa at the genus level or the next upper taxonomic level identified. The organic amendments changed the chemical properties of the restored soils, influencing the microbial communities of the restored soils. CW treatment was the organic amendment that most resembled NS, favouring in the long-term a greater diversity and proliferation of bacteria. Several bacterial communities, more abundant in NA and CW soils, were strongly correlated with each other (Craurococcus, Phaselicystis, Crossiella, etc.), forming a bacterial co-occurrence pattern (Co-occurrence pattern 1). Those bacteria showed high significant positive correlations with TOC, TN, and EC and negative correlations with the soil pH. In contrast, NA soils presented other groups of bacterial communities (Co-occurrence pattern 2) represented by Sphingomonas, Rubellimicrobium, Noviherbaspirillum, Psychroglaciecola and Caenimonas, which showed high significant positive correlations with soil pH and negative correlations with TOC, TN, and EC. The distance-based redundancy analysis indicated that SS soils remained in an intermediate stage of chemical and biological quality between NS and NA soils. Our results demonstrate that soil chemical properties and soil bacterial communities significantly changed with organic amendments in calcareous Mediterranean soils degraded by mining.


Does the implementation of clinical practice guidelines for low back and neck pain by physical therapists improve patient outcomes? A systematic review.
Physical therapy for neck and low back pain is highly variable despite the availability of clinical practice guidelines (CPG). This review aimed to determine the impact of CPG implementation on patient-level outcomes for spinal pain. Implementation strategies were also examined to determine prevalence and potential impact. Multiple databases were searched through April 2021 for studies assessing CPG implementation in physical therapy for neck and low back pain. Articles were screened for eligibility. The Modified Downs and Black checklist was utilized to determine study quality. Due to the heterogeneity between studies, a meta-analysis was not performed. Twenty-one studies were included in this review. Implementation strategies were significantly varied between studies. Outcomes pertaining to healthcare utilization, pain, and physical functioning were assessed in relation to the implementation of CPGs. Multiple implementation strategies were identified, with Managing Quality as the most frequently utilized key implementation process. Findings indicate CPG implementation decreased healthcare utilization, but inconsistent results were found with physical functioning and pain outcomes. CPG implementation appears to have a beneficial effect on healthcare utilization outcomes, but may not impact pain and physical functioning outcomes. Effective CPG implementation strategies remain unknown, though utilizing implementation framework may improve outcomes. More research is needed to determine the most effective implementation strategies and effects on pain and physical function outcomes.


Neurological expression of genetic immunodeficiencies and of opportunistic infections.
Immunodeficiencies may result from genetic defects or may be acquired after viral infection or therapeutic immunosuppression. In either case, neurological symptoms are frequent. Hemophagocytic lymphohistiocytosis (HLH), previously designated as macrophage activation syndrome (MAS), results usually from genetic defects impairing the cytotoxicity of CD8 T lymphocytes and natural killer (NK) cells. Neurological symptoms may be the first and only manifestation of the disease. The neurological and neuroradiological aspects of MAS, if isolated, may closely resemble those of other central nervous system (CNS) diseases such as acute disseminated encephalomyelitis (ADEM) or encephalitis. An early treatment including allogeneic hematopoietic stem cell transplantation can prevent further brain lesions. The main infections of the CNS observed in conjunction with therapeutic immunosuppression are described. It is important to know which phase of immunosuppression the child is in at the time of suspected CNS infection and always to consider that a relapse of the primary tumor may mimic a CNS infection.


Analysis of theFusarium toxins Deoxynivalenol and Zearalenone in Austrian feeds of the crop years 2002 and 2003.
164 feed samples were collected in Lower Austria, Upper Austria, Styria and Carynthia in the crop years 2002 and 2003 and were analysed by means of the RIDASCREEN(®) ELISA-assay for theFusarium toxins Deoxynivalenol (DON) and Zearalenone (ZON). The collected samples consisted of swine feeds, cereals and silages. DON concentrations were found up to the range of mg/kg (ppm), in contrast ZON results remained significantly lower.


A preliminary study of the rate of hospitals and satellite clinics worldwide for top US cancer centers.
Healthcare is a globalized endeavor. With an increasing number of overseas collaborations being announced as profit-driven business structures, we sought to investigate the prevalence of the top-ranked United States (US) cancer hospitals investing in overseas hospitals. We conducted a web search of publicly available information to determine the frequency in which US hospitals with top-ranked cancer centers expand into offshore markets. Of the 53 offshore entities identified, 17 (32 %) are in China. Other tops locations include Italy (9%), United Arab Emirates (8%), and Saudi Arabia (8%). Our findings show many international US-partnered clinics are located in countries designated as either high-income or upper-middle-income economies. Further research is needed to understand the full scope of US hospitals abroad and the impact it may have on the global cancer care landscape. The business-model for globalized US healthcare should be investigated for implications to local and foreign cancer care.


Silk fibroin and sericin polymer blends for sustainable battery separators.
Natural polymers are a promising alternative for reducing the environmental impact of batteries. For this reason, it is still necessary to study their behavior and implement its use in these devices, especially in separator membranes. This work reports on new separator membranes based on silk fibroin (SF) and silk sericin (SS) prepared by salt leaching method. The effect of the different SS relative content on the physiochemical properties of the membranes and on the electrochemical performance of the corresponding batteries with lithium iron phosphate (LFP) as cathodes has been reported. It is observed that the increasing of SS content leads to a decrease of the overall crystallinity of the membranes. All SF/SS membranes presented a well-defined porosity above 75% with a uniform distribution of interconnected micropores. The electrolyte uptake and the ionic conductivity are dependent on the relative SS content. The addition of 10 wt% of SS into SF membranes, induce a high ionic conductivity of 4.09 mS.cm-1 and high lithium transference number (0.52), due to the improvement of the Li+ ions conduction paths within the blended structure. Charge/discharge tests performed in Lithium/C-LFP half-cells reveal a discharge capacity of 85 mAh.g-1 at 2C after 100 cycles for batteries with a SF/SS separator, containing a 10 wt% of SS, which suggests a stabilizing effect of Sericin on discharge capacity. Further, a 50% and 35% of capacity of retention and capacity fade, respectively, is observed. The presented SF/SS membrane show high electrochemical stability, being suitable for implementation in a next generation of sustainable battery systems. This could allow the SS valorization considering that 150,000 tons of SS are abandoned each year, reducing the contamination of environmental effluents.


Apis mellifera Venom Inhibits Bacterial and Fungal Pathogens in vitro.
Background and Objective: Bacterial and fungal infections are major public health problems. Emerging of drug-resistant microbial strains urges the need for the development of alternative untraditional antimicrobial agents. Bee venom is a rich source of secondary metabolites and antimicrobial agents. In this study, the antimicrobial and antifungal potential of Apis mellifera BV (AmBV) against some medically important bacterial and fungal pathogens was investigated. Materials and Methods: Broth microdilution method and Colony Forming Unit (CFU) assay were used to screen the antibacterial potential of AmBV. Similarly, the antifungal activity of AmBV was evaluated using the agar-well diffusion assay. Moreover, the minimum inhibitory concentration (MIC) values of AmBV against tested microorganisms were determined. Results: AmBV significantly inhibited bacterial and fungal growth. The MIC values of AmBV were 15.625, 31.25, 7.8, 7.8 μg mL1 against Escherichia coli ATCC 8739, Staphylococcus aureus ATCC 6538P, Serratia marcescens AUH 98 and Streptococcus mutans ATCC 25175, respectively. Similarly, AmBV at concentrations of 300 and 600 μg mL1 significantly inhibited the growth of Aspergillus niger ATCC 16404, Alternaria alternata MLBM09, Fusarium oxysporum MLBM212 and Aspergillus flavus. Conclusion: These results indicated that AmBV could be used in future preclinical and clinical studies to develop cost-effective and efficient antibacterial and antifungal agents. Moreover, this study presents AmBV as an efficient alternative antimicrobial agent against medically important pathogens.


Trends, Burden, and Impact of Arrhythmias on Cardiac Transplant Recipients: A 16-year Nationwide Study.
Orthotopic heart transplantation is the most effective long-term therapy for end-stage heart disease. Denervation with the loss of autonomic modulation, vasculopathy, utilization of immunosuppressant drugs, and allograft rejection may result in an increased prevalence of arrhythmias in transplanted hearts. We aim to describe the trends, distribution, and the clinical impact of arrhythmias in patients with transplanted hearts. We queried the National Inpatient Sample with administrative codes for cardiac transplant patients using procedure ICD-9-CM codes 37.5 and 33.6. Arrhythmias were extracted using validated ICD-9-CM codes. Statistical Analysis System (SAS) version 9.4 was used for analysis. There were a total of 30,020 hospitalizations of heart transplant recipients between 1999 and 2014 in the United States of which 1,6342 (54.4%) had an arrhythmia. The frequency of total arrhythmias increased from 53.6% (n=1,158) in 1999 to 67.3% (n=1,575) in 2014. Transplant patients with arrythmias was not associated with significantly higher inpatient mortality (7.72% vs 6.90%, P = 0.225). The most common arrythmia was atrial fibrillation ([AF]26.83%) followed by ventricular tachycardia (22.86%). Trends in mortality associated with arrhythmias following heart transplant has been decreasing from 12.3% in 1999 to 8.9% in 2014 (P = 0.04). Subgroup analysis of ventricular arrythmias (VA) following heart transplant were associated with increased mortality (8.61% vs 6.94%, P = 0.0229). Over half of patients develop 1 or more cardiac arrhythmia after heart transplant. There is an increasing secular trend in the frequency of arrhythmias post cardiac transplant with atrial fibrillation determined to be the most common arrhythmia.


Analysis of dynamic hepatobiliary contrast-enhanced MRI signal intensity after Yttrium-90 radioembolization with glass microspheres for the treatment of hepatocellular carcinoma.
To analyze hepatobiliary specific contrast agent (HBA) dynamic MRI signal intensity (SI) differences between treated liver (TL) and untreated liver (UL) parenchyma in patients following transarterial radioembolization (TARE) for hepatocellular carcinoma (HCC) using yttrium-90 containing glass microspheres. This was a single institution retrospective study of patients with HCC treated with lobar or segmental TARE who received pre- and post-treatment HBA multiphase MRI within a 3-year period. Patients with prior locoregional therapies or multiple TAREs were excluded. SI was obtained by drawing a 2D ROI on T1-weighted non-contrast, arterial (25 s.), portal venous (60 s.), transitional (180 s.), and hepatobiliary (HB) (1200 s.) phase sequences in the (TL) angiosome and UL. HB phase signal enhancement characteristics were correlated with TARE dose thresholds (< 120 Gy, 120-190 Gy, and > 190 Gy) using the medical internal radiation dose (MIRD) methodology. 282 patients received TARE using glass microspheres during the study period and 58 patients who met inclusion criteria were analyzed. Median dose was 141.5 Gy MIRD [IQR 122.0, 161.5; range 100-540 Gy]). Statistically significant differences were present between treated and non-treated liver on non-contrast (- 28.0, p = 0.003), arterial (38.5, p = 0.013), and HB phases (- 95.8, p ≤ 0.001). Median follow-up time to furthest post-treatment MRI was 6 months (range 3-11 months). There was no significant SI difference on portal venous or transitional phases. HB phase SI changes in the TL compared to UL were significant at all TARE dose thresholds (p < 0.05). SI differences between treated and untreated liver after TARE are most significant on the HB phase and present at all evaluated dose levels at a median of 6 months after treatment. These findings support the parenchymal ablative potential for TARE and the necessity to consider liver function loss within targeted liver volumes.


Effects of rice straw structure on chaetoglobosin A production by Chaetomium globosum CGMCC 6882.
As the most abundant macromolecules in nature, lignocelluloses are served as a promising and renewable source for sustainable production of high value chemical compounds. In present work, extrusion pretreatment with 23% (w/w) distilled water, 2% (w/w) glycerol and 1 g/L NaHCO3 as moisture agent, not only reduced the particle size, crystallinity and component contents (cellulose, hemicelluloses and lignin) of rice straw, but also effectively enhanced chaetoglobosin A yield and degradation rate of rice straw by C. globosum CGMCC 6882. Meanwhile, mycelial biomass of C. globosum CGMCC 6882 increased from 2.9 g/L to 7.0 g/L, mycelia growth time reduced by 2 days and chaetoglobosin A titer increased from 108.4 mg/L to 270.2 mg/L, representing an increase of 149.3%. Furthermore, degradation rate of rice straw by C. globosum CGMCC 6882 increased from 28.93% to 65.38%. This work provides a good guidance for production of chaetoglobosin A from lignocelluloses.


Accelerated Peri-Implant Soft Tissue Conditioning With Computer-Aided Design and Computer-Aided Manufacturing Technology and Surgical Intervention: A Case Report.
The conventional soft tissue conditioning technique around implant demands time and effort for optimizing soft tissue contour. This article describes an alternative technique for achieving proper emergence profile with a custom-milled titanium abutment, interim restoration, and surgical intervention. With this technique, peri-implant soft tissue is conditioned and healed against a correct designed interim restoration without composite resin addition.


Orexin-1 receptor antagonism fails to reduce anxiety-like behaviour in either plus-maze-naïve or plus-maze-experienced mice.
Although several lines of evidence have recently implicated orexins and their receptors in fear and anxiety, there is also a growing number of apparently inconsistent and/or negative findings. In the present study, we have used ethological methods to comprehensively profile the behavioural effects of the orexin-1 receptor antagonist SB-334867 (3-30 mg/kg) in mice exposed to the elevated plus-maze. Two experiments were performed, the first involving test-naïve animals and the second using prior undrugged experience of the maze to induce a qualitatively different emotional response to that seen on first exposure. In Experiment 1, a reference benzodiazepine (chlordiazepoxide, CDP, 15 mg/kg) produced a robust anxioselective profile comprising substantial increases in open arm exploration and reduced risk assessment without any signiifcant change in general activity levels. In contrast, SB-334867 failed to produce any behavioural effects over the dose range tested. In Experiment 2, 5 min undrugged experience of the maze 24h prior to testing increased open arm avoidance and abolished the anxiolytic efficacy of CDP. Despite this altered baseline, SB-334867 again failed to alter plus-maze behaviour. These findings agree with several recent reports that orexin receptor antagonists, such as SB-334867 and almorexant, do not alter basal anxiety levels in rats but markedly contrast with the anxiolytic-like effects of the same agents when anxiety levels have been exacerbated by fear conditioning, drug challenge or hypercapnia. This unique pattern of activity suggests that orexin receptor antagonists may have therapeutic value in those clinical anxiety disorders characterised by intense emotional arousal.


Malpractice litigation in elective lumbar spinal fusion: a comprehensive review of reported legal claims in the U.S. in the past 50 years.
In the U.S., medical malpractice litigation is associated with significant financial costs and often leads to the practice of defensive medicine. Among medical subspecialities, spine surgery is disproportionately impacted by malpractice claims. To provide a comprehensive assessment of reported malpractice litigation claims involving elective lumbar spinal fusion (LSF) surgery during the modern era of spine surgery instrumentation in the U.S., to identify factors associated with verdict outcomes, and to compare malpractice claims characteristics between different approaches for LSF. A retrospective review. Patients undergoing elective lumbar spinal fusion surgery. The primary outcome measure was verdict outcome (defendant vs. plaintiff verdict). Secondary outcome measures included alleged malpractice, injury/damage claimed, and award payouts. The Westlaw legal database (Thomson Reuters, New York, NY, USA) was queried for verdict and settlement reports pertaining to elective LSF cases from 1970 to 2021. Data were collected regarding patient demographics, surgeon specialty, fellowship training, state/region, procedure, institutional setting (academic vs. community hospital), alleged malpractice, injury sustained, case outcomes, and monetary award. A total of 310 cases were identified, yielding 67% (n=181) defendant and 24% (n=65) plaintiff verdicts, with 9% (n=26) settlements. Neurosurgeons and orthopedic spine surgeons were equally named as the defendant (45% vs. 51% respectively, p=0.59). When adjusted for inflation, the median final award for plaintiff verdicts was $1,241,286 (95% CI: $884,850-$2,311,706) while the median settlement award was $925,000 (95% CI: $574,800-$1,787,130), with no stastistically significant differences between verdict and reported settlement payouts (p=0.49). The Northeast region displayed significantly higher award payouts compared to other U.S. regions (p=0.02). There were no associations in awards outcomes when comparing alleged malpractice, alleged injuries/damages, institutional setting, surgical procedures, and surgeon specialty or fellowship training. The most common claims were intraoperative error (28%, n=107) followed by failure to obtain informed consent (24%, n=94). In the analyzed cohort, the most common injuries leading to litigation were refractory pain and suffering (37%, n=149) followed by permanent neurological deficits (26%, n=106). There were no differences in alleged malpractice or injury sustained between cases in which the outcome was favorable to defendant versus plaintiff. Anterior lumbar interbody fusion (ALIF) cases were 2.75 times more likely to be cited for excessive or inappropriate surgery (OR: 2.75 [95% CI: 1.14, 6.86], p=0.02) when compared to posterior surgical approaches. The results of our analysis of reported claims suggest that medical malpractice litigation involving elective LSF is associated with jury verdicts over $1 million per case, with the most common alleged malpractice being intraoperative error and failure to obtain informed consent. Surgeon specialty, fellowship training, procedure type, and institution type were not associated with greater litigation risks; however, ALIF surgery had a significantly higher risk of involving claims of excessive or inappropriate surgery compared to posterior approaches for lumbar fusion. In addition, claims were significantly higher in the Northeast compared to other U.S. regions. Efforts to improve patient education through shared-decision making and proactive strategies to avoid, detect, and mitigate intra-operative procedural errors may decrease the risk of litigation in elective LSF.


Increased intracellular Ca2+ decreases cisplatin resistance by regulating iNOS expression in human ovarian cancer cells.
Previous studies have reported that intracellular Ca2+ signals and inducible nitric oxide synthase (iNOS) are involved in cell apoptosis. However, the role of iNOS in cisplatin resistance in ovarian cancer remains unclear. Here, we demonstrate that SKOV3/DDP ovarian cancer cells were more resistant to cisplatin than were SKOV3 ovarian cancer cells. The expression of intracellular Ca2+ and iNOS was more strongly induced by cisplatin in SKOV3 cells than in SKOV3/DDP cells. TAT-conjugated IP3R-derived peptide (TAT-IDPS) increased cisplatin-induced iNOS expression and apoptosis in SKOV3/DDP cells. 2-Aminoethoxydiphenyl borate (2-APB) decreased cisplatin-induced iNOS expression and apoptosis in SKOV3 cells. Thus, iNOS induction may be a valuable strategy for improving the anti-tumor efficacy of cisplatin in ovarian cancer.


Immobilization of phospholipase D on macroporous SiO2/cationic polymer nano-composited support for the highly efficient synthesis of phosphatidylserine.
Novel nano-composites were prepared by coating epoxy resin-based cationic polymer in nano-thickness via in-situ curing on the nano-wall of macroporous SiO2 with pore size of 0.5∼1 μm. By changing the thickness of polymer coating the specific surface area and porosity varied in range of 115∼74 m2/g and 90.4∼83.9 %, respectively. Through ion exchange phospholipase D (PLD, from Streptomyces sp) was efficiently immobilized on the nano-composites as support and the immobilized PLD was applied for the highly efficient synthesis of phosphatidylserine (PS). The loading amount of PLD on the nano-composited support reached to a maximum of 90.2 mg/gsupport, 4 times as high as that on the pure macroporous silica. The specific activity of the immobilized PLD reached as high as 16,230 U/gprotein, while that of free PLD was 18,780 U/gprotein. Under a wide range of temperature and pH the stability and activity of the immobilized PLD were greatly improved as compared with the free ones. Under optimized conditions at 45 °C and pH 7.0, the PS yield reached as high as 96.2 % within 40 min. After 28 days storage the immobilized PLD retained 82.2 % of original activity, and after 12 cycling reuses it retained 79.3 % of PS yield, which indicated that the immobilized PLD exhibited good stability.


Allergic rhinitis--history and presentation.
Allergic rhinitis is a common disorder that results from a complex interaction of environmental and genetic causes. This disorder has a tremendous impact on the quality of life and on health care expenditures, as evidenced by a large loss of worker productivity. Care must be taken to promptly diagnose patients with this condition, evaluate them for associated conditions, and begin appropriate management to reduce its impact on the individual and the health care system. Allergic rhinitis represents only a component of the spectrum of inflammatory diseases involving the unified airway.


Single voxel proton MR spectroscopy findings of typical and atypical intracranial meningiomas.
To prospectively define proton magnetic resonance spectroscopy (MRS) findings of meningiomas, and describe the ability or inability of short- and long-echo MRS to differentiate typical and atypical meningiomas in vivo. Seventeen patients with pathologically confirmed typical meningiomas and six with atypical meningiomas were evaluated with conventional MR imaging and MRS before resection. MRS studies using point-resolved spectroscopy (PRESS) localisation, at short- and long-echo time (TR 2000 ms, TE: 30 and 144 ms, 64-96 acquisition) were acquired on a 1.5 T scanner. MRS data obtained from these patients were compared with histopathological findings. Mean cellular proliferation (MIB-1) antibody staining against the Ki-67 antigen was also determined in all meningiomas. Prominent choline (Cho) was present in all meningiomas. Alanine (Ala) was observed in 21 cases of the 23 meningiomas. Acetylaspartate (NAA) and creatine (Cr) were either not observed or detected in minimal amounts in at all both groups of meningiomas on long TE (144 ms) spectra. The mean Cho/Cr values in the four atypical meningiomas were 4.44+/-0.30 (mean+/-standard deviation) and 3.39+/-0.52 in the 12 typical meningiomas on short TE spectra. Cho/Cr ratio could not be determined in the other seven cases because of a lack of creatine peak. Of the five meningiomas in which a lactate peak was detected, four were in typical cases and only one was in atypical meningioma. Mean MIB-1 proliferation index was 3.7% in typical meningiomas and 10% in atypical meningiomas. Prominent Cho, absence or low amount of NAA and Cr, and presence of Ala were common characteristics of spectral pattern of both atypical and typical meningiomas on MRS. MRS cannot reliably differentiate typical intracranial meningiomas from atypical meningiomas preoperatively. Mean MIB-1 proliferation index was well correlated with histopathology findings.


Relationship between Health Costs and Inflammatory Profile in Public Health.
The association between obesity and physical activity level is well established in the literature, as well as its consequences that lead to chronic noncommunicable diseases. In addition, it is also possible to obtain the immunometabolic mechanism that explains the pathway of associations between obesity, chronic noncommunicable diseases and the level of physical activity. It also seems clear that treating illnesses has a financial impact on healthcare systems around the world, so it seems important to assess the financial impact on the healthcare system of individuals with immunometabolic dysfunction. This study aimed to assess whether there is a correlation between metabolic and inflammatory markers and healthcare costs according to body adiposity and habitual physical activity (HPA). This is a cross-sectional study, where the sample includes men and women aged over 50. Participants underwent evaluations that included the following variables: i) immunometabolic markers, ii) healthcare costs, iii) obesity, iv) habitual physical activity, and v) history of personal illness. Statistical significance was set at values lower than 5% and the software used was BioEstat. The correlation between metabolic and inflammatory markers and healthcare costs demonstrated a positive and significant relationship, adjusted for obesity and HPA, between glucose concentrations and exam costs (r = 0.343, p-value = 0.007) and total cost (r = 261; p-value = 0.043); HOMA index and cost of exams (r = 0.267; pvalue = 0.038); and IL-10 and cost of medical consultation (r = 0.297; p-value = 0.020). Metabolic and inflammatory markers may be related to the costs of consultations and examinations, independent of obesity and HPA.


Robotics in otolaryngology and head and neck surgery: Recommendations for training and credentialing: A report of the 2015 AHNS education committee, AAO-HNS robotic task force and AAO-HNS sleep disorders committee.
Training and credentialing for robotic surgery in otolaryngology - head and neck surgery is currently not standardized, but rather relies heavily on industry guidance. This manuscript represents a comprehensive review of this increasingly important topic and outlines clear recommendations to better standardize the practice. The recommendations provided can be used as a reference by individuals and institutions alike, and are expected to evolve over time. © 2016 Wiley Periodicals, Inc. Head Neck 38: E151-E158.


Lysophosphatidylcholine accumulation in the ischemic canine heart.
The production of cardiac arrhythmias and the elevation of lysophosphatidylcholine level in the ischemic myocardium have been well-documented in a number of studies. However, the relationship between the production arrhythmias and the elevation of tissue lysophosphatidylcholine level was not reported. In this study, the lysophosphatidylcholine level and the occurrence of cardiac arrhythmias in the ischemic canine heart were monitored. A temporal relationship between the accumulation of lysophosphatidylcholine and the occurrence of arrhythmias was established after five hr of ischemia. A significant elevation of lysophosphatidylcholine was detected at three hr of ischemia without the occurrence of arrhythmias. The results indicate that cardiac arrhythmias did not cause the elevation of lysophosphatidylcholine and if lysophospholipids are causally related to the arrhythmias that a critical level of the lysophospholipid must accumulate in order to elicit electrophysiological alterations.


Gene dose of apolipoprotein E and age-related hearing loss.
Next to outer hair cell dysfunction, age-related hearing loss may be explained by apolipoprotein E (APOE) genotype. In the Leiden 85-plus Study, a population-based study, the participants were 85 years old. We measured hearing loss by pure-tone audiometry in 435 participants in relation to APOE. Results demonstrated that those with the APOE-ε4/ε4 genotype had the highest levels of hearing loss (n = 6; 56.1 dB), those with the APOE-ε3/ε4 or ε2/ε4 genotype (n = 89) had intermediate levels of hearing loss (51.0 dB), and those without the APOE-ε4 allele (n = 340) had the lowest levels of hearing loss (48.9 dB), p for trend = 0.02. Eighty percent of participants had hearing loss of 35 dB and more, that is, hearing impairment. The APOE-ε4 allele was associated with a 2.0-fold increased risk of hearing impairment (confidence interval [CI 95%], 1.0-4.0), compared with those without the APOE-ε4 allele. The risk for hearing impairment in subjects with the APOE-ε4 allele remained similar after adjustment for cardiovascular disease, stroke, and cognitive impairment. Our results suggest that the APOE-ε4 allele contributes to age-related hearing loss.


The omentum in the management of complicated cardiothoracic problems.
The pedicled omentum finds use in cardiothoracic surgery for management of complicated problems and prevention of serious complications. Its blood supply is excellent and is capable of inducing neovascularity. Based on the right gastroepiploic artery, it reaches anywhere in the thorax or neck. Its bulk helps to fill infected spaces. Thirty-seven patients have been treated with the pedicled omentum. In 16 patients the goal was preventive, to avoid bleeding, anastomotic leakage, or infection or to provide a source of fibroplasia or neovascularity. In eight patients with cervical exenteration the flap protected against innominate artery erosion and esophageal leakage, generally in an irradiated field. In six patients it permitted primary healing of heavily irradiated trachea--formerly unlikely. It was also used to provide coverage of a chest wall prosthesis in two patients. In 21 patients the omentum was used to obtain healing in the presence of infection. Bronchopleural fistulas were successfully closed in eight of nine patients. Six mediastinal infections that developed after cardiac operations were successfully treated. Four unusual vascular infections necessitated the use of omentum. Two patients had closure of esophageal perforations buttressed with omentum. This series demonstrates the efficacy of the omentum in the management of complex cardiac, vascular, esophageal, tracheal, bronchial, pleural, and chest wall problems.


Membrane-assisted radiant cooling for expanding thermal comfort zones globally without air conditioning.
We present results of a radiant cooling system that made the hot and humid tropical climate of Singapore feel cool and comfortable. Thermal radiation exchange between occupants and surfaces in the built environment can augment thermal comfort. The lack of widespread commercial adoption of radiant-cooling technologies is due to two widely held views: 1) The low temperature required for radiant cooling in humid environments will form condensation; and 2) cold surfaces will still cool adjacent air via convection, limiting overall radiant-cooling effectiveness. This work directly challenges these views and provides proof-of-concept solutions examined for a transient thermal-comfort scenario. We constructed a demonstrative outdoor radiant-cooling pavilion in Singapore that used an infrared-transparent, low-density polyethylene membrane to provide radiant cooling at temperatures below the dew point. Test subjects who experienced the pavilion (n = 37) reported a "satisfactory" thermal sensation 79% of the time, despite experiencing 29.6 ± 0.9 °C air at 66.5 ± 5% relative humidity and with low air movement of 0.26 ± 0.18 m⋅s-1 Comfort was achieved with a coincident mean radiant temperature of 23.9 ± 0.8 °C, requiring a chilled water-supply temperature of 17.0 ± 1.8 °C. The pavilion operated successfully without any observed condensation on exposed surfaces, despite an observed dew-point temperature of 23.7 ± 0.7 °C. The coldest conditions observed without condensation used a chilled water-supply temperature 12.7 °C below the dew point, which resulted in a mean radiant temperature 3.6 °C below the dew point.


Ovarian cancer emerging subtypes: role of oxidative stress and fibrosis in tumour development and response to treatment.
Epithelial ovarian cancer is a silent disease of usually late diagnosis and poor prognosis. Currently treatment options are limited and mainly consist of surgery followed by taxol- and platinum-based chemotherapy. Patient response to treatment is difficult to predict and there is a serious need for anticipating tumour response and orientating medical choices. In that aim, recent researches have focused on molecular aspects of ovarian tumours that could help patient stratification. We review here published discoveries in that field. We emphasize that signatures, defined by combining miRNA and transcriptomic data, enlighten important aspects of ovarian cancer biology and reliably stratify patients. The miR-200-dependent "Oxidative stress" and "Fibrosis" signatures are promising in patient stratification for defining oriented therapeutic strategies. Indeed, the "Stress" patients survive longer than the "Fibrosis" patients, who exhibit partial debulking and incomplete response to chemotherapy. Interestingly, these two subgroups might benefit from specifically targeted therapeutic approaches, as discussed here.


Regulation of ornithine decarboxylase expression by anisosmotic shock in alpha-difluoromethylornithine-resistant L1210 cells.
Ornithine decarboxylase (ODC) activity is known to be strongly enhanced in mammalian cells by a sudden reduction in ambient osmolality. The effect of hypoosmotic shock on the regulation of ODC protein and mRNA levels was studied in a variant L1210 mouse leukemia cell line (D-R cells) which expresses ODC at greater than or equal to 100-fold higher levels than the parental cells. Hypoosmotic stress increased ODC activity in proportion with the osmotic gradient imposed to both D-R cells and their normal counterparts. A 60% decrease in medium osmolality increased ODC activity and the amount of immunoreactive ODC protein from 20- to 30-fold after 4 h without any detectable change in ODC mRNA contents in D-R cells. ODC induction was sustained up to 48 h after hypoosmotic shock, with maximal activity levels being observed at 24 h. Hypotonic shock dramatically increased (up to 36-fold) the rate of ODC synthesis as measured by 10-min pulses with 35S-labeled methionine, in agreement with kinetic constants predicted from the changes observed for the enzyme activity. Moreover, hypoosmotic stress extended the half-life of ODC activity from 35 +/- 10 to 212 +/- 67 min and blocked any degradation of the radiolabeled immunoreactive protein, which had a half-life of 28 +/- 6 min under isotonic conditions, for at least 120 min after addition of cycloheximide. The induction of ODC by hypoosmotic stress was quickly reversed by a sudden upshift of osmolality through a very rapid inhibition of ODC biosynthesis and an increase in the rate of enzyme degradation. Thus, hypoosmotic stress activates the expression of ODC exclusively through post-transcriptional mechanisms in D-R cells. The osmotically induced accumulation of ODC molecules is quite unique as shown by the fact that ODC is the major protein (approximately 25% of total) synthesized during the first 4 h following a 60% hypotonic shock, despite a 30-50% reduction of the rate of labeled precursor incorporation into soluble proteins.


The validity of the transdiagnostic cognitive behavioural model of eating disorders in predicting dietary restraint.
The study examined the validity of the transdiagnostic cognitive behavioural theory of eating disorders. The aim was to determine if the maintaining mechanisms of clinical perfectionism, core low self esteem, mood intolerance and interpersonal difficulties have a direct impact on dietary restraint or an indirect impact via eating, shape and weight concerns. The model was tested in a community sample of 224 females recruited via the internet. The structural equation model provided a good fit for the data. The relationship between maintaining mechanisms and dietary restraint was due to maintaining mechanisms impacting indirectly on dietary restraint via eating disorder psychopathology. The results lend support for the validity of the transdiagnostic model of eating disorders as the maintaining mechanisms lead to restraint via the core psychopathology of eating concerns, weight concerns and shape concerns. The findings suggest the four maintaining mechanisms alone are not enough to lead to dietary restraint, the core psychopathology of eating disorders needs to be present, which supports the predictions of the theory. These results help establish the validity of the transdiagnostic cognitive behavioural theory of eating disorders.


Short-term metabolic changes achieved by weight loss in hypertensive patients.
Glucose and lipid metabolism abnormalities of hypertensive patients are highly relevant due to its increase in cardiovascular risk; moreover, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) have a high risk of new-onset diabetes mellitus (DM) development. The objective of the study was to describe glucose metabolism abnormalities and the impact of mid-term weight loss. A six-month prospective, observational and multicentre study of patients with hypertension was conducted. Clinical antecedents, physical examination, blood test and treatments were collected in two separated visits; conventional advice was the only intervention planned. A total of 1957 patients were included, mean age 66.3 (10.9) years and 59.9% males. A previous diagnosis of glucose metabolism alteration was present in 43.9% (25.5% type-2 DM, 14.8% IFG, 1.6% IFG and IGT, 1.0% IGT and 1.0% type-1 DM). An increasing pattern of cardiovascular risk and target organ damage was observed according to the categories of fasting glucose. Oral glucose tolerance test (OGTT) was carried out in 234 patients (11.9%) patients and yielded the diagnosis of IGT in 44.7% or DM in 22.4% of patients with fasting glucose >100mg/dl. Six months follow-up was achieved in 85.9% patients. A slight reduction in fasting glucose was observed in the whole cohort and patients who achieved ≥ 5% weight loss experienced the highest reduction in fasting glucose, LDL-c and triglycerides; moreover, 15.8% normalized their IFG. Glucose and lipid metabolism abnormalities are highly prevalent in hypertensive patients and improve with 5% of weight lost at 6 months follow-up. OGTT is not currently extended in daily clinical practise.


Immediate and long-term results following repair of aortic left ventricular discontinuity: a 25-year experience.
From 1967 to 1993, 21 patients underwent surgical repair of aortic left ventricular discontinuity as a result of acute bacterial endocarditis. Repair of the defect between the aorta and left ventricle was usually with interposition of a patch (prosthetic patch or autologous pericardium), using a continuous monofilament suture. Interrupted pledgetted stitches were used when the ventricular tissue appeared friable. A valve prosthesis was then sewn to the patch and remaining annulus. Three patients died in the immediate perioperative period. Long follow-up ranging from 5 to 142 months (mean 36 months) is available on 17 of 18 survivors. There were six deaths in this group from 11 to 142 months (mean 67 months) from initial surgery. Of 11 long-term survivors (5 to 61 months (mean 21 months) after operation), nine have had event-free courses. Two cases of recurrent subacute bacterial endocarditis occurred 3 and 52 months after surgery in patients who were intravenous drug abusers, both of whom were managed medically. It is concluded that while aortic left ventricular discontinuity remains a potentially lethal complication of acute bacterial endocarditis, débridement of infected necrotic tissue, patch repair of the defect, and prosthetic valve replacement offer satisfactory immediate and late results.


Epidemiology of ovine helminthiasis in Haryana, India.
Tracer lambs were used to study the pasture contamination with infective stages of helminth parasites during one annual cycle in a subtropical climate. Post-mortem worm counts indicated that low infections with Haemonchus contortus occurred throughout the year except in June. However, twenty five or more H. contortus per lamb were recorded in January, April, May and August. Trichostrongylus colubriformis infection was detected throughout the year and 150 or more worms per lamb were recorded during January to May and in August. Anoplocephalids were recorded from the lambs throughout the year but had no seasonal pattern. Low infections with Oesophagostomum columbianum and Trichuris ovis were observed. The faecal egg counts from the permanent flock with whom the tracer lambs were grazed revealed heavy to mild worm burdens throughout the year. Coproculture indicated that H. contortus predominated from the second fortnight of May to December except in the second fortnight of July. Infection with T. colubriformis was more severe from January to the first fortnight of May and in the second fortnight of July. Negligible infections with O. columbianum, Bunostomum trigonocephalum, Gaigeria pachyscelis and Dictyocaulus filaria were also observed. Biohythergraphs prepared for H. contortus and T. colubriformis showed differences between observed and expected results. It is suggested that for realistic biohythergraphs related parameters in addition to rainfall and temperature should also be considered.


Control of DNA photocleavage by oligothiazole derivatives.
Mechanism of DNA damage by the p-cyanobenzamide (pCyBz)-oligothiazole derivatives were investigated by HPLC analysis. The oxidation product of dG by the photocleaver was imidazolone (dIz).


Deciphering the degradation characteristics of the fungicides imazalil and penflufen and their effects on soil bacterial community composition, assembly, and functional profiles.
The adsorption-desorption and degradation characteristics of two widely applied fungicides, imazalil and penflufen, and the responses of soil bacterial diversity, structure, function, and interaction after long-term exposure were systemically studied in eight different soils. The adsorption ability of imazalil in soil was significantly higher than that of penflufen. Both imazalil and penflufen degraded slowly in most soils following the order: imazalil > penflufen, with soil pH, silt, and clay content being the potential major influencing factors. Both imazalil and penflufen obviously inhibited the soil microbial functional diversity, altered the soil bacterial community and decreased its diversity. Although exposure to low and high concentrations of imazalil and penflufen strengthened the interactions among the soil bacterial communities, the functional diversity of the co-occurrence network tended to be simple at high concentrations, especially in penflufen treatment. Both imazalil and penflufen markedly disturbed soil nitrogen cycling, especially penflufen seriously inhibited most nitrogen cycling processes, such as nitrogen fixation and nitrification. Meanwhile, sixteen and ten potential degradative bacteria of imazalil and penflufen, respectively, were found in soils, including Kaistobacter and Lysobacter. Collectively, the long-term application of imazalil and penflufen could cause residual accumulation in soils and subsequently result in serious negative effects on soil ecology.


Bladder outlet obstruction due to labial agglutination.
Here, we report the case of a 63-year-old female patient who presented with emptying symptoms and was subsequently diagnosed with delayed labial agglutination. The adhered labia minora were divided by blunt dissection, and a topical estrogen ointment was applied after surgery. The patient's voiding symptoms were completely resolved and no recurrence of labial agglutination was noted 3 months after surgery. Labial agglutination is rare but often manifests with nonspecific emptying symptoms. Nevertheless, it can be easily diagnosed on physical examination and successfully treated by surgical intervention and the application of a local estrogen ointment. We present this rare case in order to emphasize the importance of physical examination.


Using the National Health Information Database of the National Health Insurance Service in Korea for Monitoring Mortality and Life Expectancy at National and Local Levels.
This study explores whether the National Health Information Database (NHID) can be used to monitor health status of entire population in Korea. We calculated the crude mortality rate and life expectancy (LE) at birth across the national, provincial, and municipal levels using the NHID eligibility database from 2004 to 2015, and compared the results with the corresponding values obtained from the Korean Statistical Information Service (KOSIS) of Statistics Korea. The study results showed that the ratio of crude mortality rate between the two data was 0.99. The absolute difference between the LE of the two data was not more than 0.5 years, and did not exceed 0.3 years in gender specific results. The concordance correlation coefficients (CCC) between the crude mortality rates from NHID and the rates from KOSIS ranged 0.997-0.999 among the municipalities. For LE, the CCC between the NHID and KOSIS across the municipalities were 0.990 in 2004-2009 and 0.985 in 2010-2015 among men, and 0.952 in 2004-2009 and 0.914 in 2010-2015 among women, respectively. Overall, the NHID was a good source for monitoring mortality and LE across national, provincial, and municipal levels with the population representativeness of entire Korean population. The results of this study indicate that NHID may well contribute to the national health promotion policy as a part of the health and health equity monitoring system.


Compensatory branching and changes in nitrogen content in the aquatic weed Salvinia molesta in response to disbudding.
Secondary side branching in Salvinia molesta plants grown in nutrient solution was dependent on the availability of nitrogen. The compensatory response of S. molesta to damage by complete manual disbudding was the production of extensive secondary side branching at nitrogen levels below those required for this type of branching in undamaged plants. After 28 days damaged plants had the same number of ramets as undamaged plants but the dry weight was considerably reduced.After 7 days there was no change in dry weight with partial or complete disbudding. However completely disbudded plants had no new ramets and plants with all terminal buds removed had numbers of ramets significantly reduced. The concentration of nitrogen in the tissue of new growth was higher in damaged than undamaged plants. The results are discussed in relation to the biological control of S. molesta by the bud-eating weevil, Cyrtobagous salviniae.


[Lumbar disc arthroplasty. Established technique or experimental procedure?].
Lumbar interbody fusion used to be the most common surgical treatment for painful lumbar disc degeneration. With the technical development of total disc prostheses, replacement of the degenerated disc by a motion preserving implant has become a widely discussed alternative. The advantages of such replacement appear to include the prevention of adjacent segment disease as well as less perioperative morbidity. Three types of total disc prostheses are currently in common use. Although numerous studies have been made, a review of the literature reveals only two multicenter randomized studies comparing the outcome of disc prostheses with a control group of fusion patients. After 2 years, the available results show similar improvement after both types of surgery without significant differences. However, there is a trend towards faster recovery and improvement in disc arthroplasty patients. The long-term results of current and future randomized studies, including studies comparing results after disc arthroplasty, with results of standardized conservative therapies will determine the fate of lumbar disc prostheses.


Mast cell tryptase and photoaging: possible involvement in the degradation of extra cellular matrix and basement membrane proteins.
Mast cells are widely distributed in the connective tissue of the body, but are particularly prominent in tissues such as skin. An increased number of mast cells can be found in the dermis under inflammatory conditions and ultraviolet (UV) exposed skin. Previous investigations have identified matrix metalloproteinases (MMPs) as key enzymes in the degradation of extra cellular matrix (ECM). This study reports about the potential contribution of human mast cell tryptase as a new triggering enzyme in matrix degradation process. Recent studies suggest that mast cell-derived proteases can activate MMPs. We investigated both the degradation of cellular matrix components and activation of MMPs by human tryptase. Mast cells are increased in photoaged skin and the increase of mast cell tryptase in UV irradiated skin was confirmed. Human mast cell tryptase was purified from human tonsils by a series of standard chromatographic procedures. Degradation of collagen type I was achieved by incubation of human type I collagen with tryptase and the fragments were quantified by SDS-PAGE and staining with Coomassie Brilliant Blue 250-R (CBB). Treatment with tryptase resulted in the activation of proMMP-9 as revealed by gelatinolytic activity in type IV collagen zymography. When tryptase was incubated with human type IV collagen, gradual degradation of intact collagen was detected by Western blotting. Furthermore, type IV collagen degradation was observed in the basement membrane (BM) of a three-dimensional (3D) skin model. Degranulation of mast cells, which release tryptase, can activate MMPs and causes direct damage to ECM proteins. These findings strongly implicate that tryptase either alone or in conjunction with activation of MMPs, can participate in ECM damage and the possible destruction of BM leading to photoaging.


Brief Report: Patterns and Secular Trends in Use of Immunomodulatory Agents During Pregnancy in Women With Rheumatic Conditions.
To describe patterns and secular trends in the use of immunomodulatory agents in pregnant women with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), psoriatic arthritis (PsA), or ankylosing spondylitis (AS). We identified a cohort of women with SLE, RA, PsA, or AS enrolled in public (Medicaid, 2001-2010) or private (Optum Clinformatics, 2004-2012) health insurance, and we included women filling prescriptions for immunomodulatory agents (including steroids, nonbiologic disease-modifying agents, and biologic agents) in the 3-month period immediately prior to their pregnancies. The proportion of women continuing or discontinuing individual agents during pregnancy was reported. Annual prescription fill rates, estimated after accounting for patient characteristics and random variability from year to year in mixed-effects regression models, were used to conduct time trends analysis. We included 2,645 women being treated with immunomodulatory agents prior to pregnancy. More women with PsA or AS stopped filling prescriptions for immunomodulatory agents during pregnancy (61%) than women with SLE (26%) or women with RA (34.5%). From the first to the third trimester, the proportions of women filling prescriptions for immunomodulatory agents decreased across all indications. Overall, steroids and hydroxychloroquine were the most frequently used agents in pregnancy (48.4% and 27.1%, respectively). The rates (reported per 100 deliveries in our cohort) for steroid prescription fills during pregnancy decreased significantly from 54.4 in 2001 to 42.4 in 2012, while rates for biologic agents increased from 5.1 in 2001 to 16.6 in 2012 (P < 0.001 for both trends). Steroids and hydroxychloroquine remain the most widely prescribed treatment options in pregnancy, but the use of biologic agents is becoming increasingly common.


The RON and MET oncogenes are co-expressed in human ovarian carcinomas and cooperate in activating invasiveness.
RON is a member of the receptor tyrosine kinase gene family that includes the MET oncogene, whose germline mutations have been causally related to human tumorigenesis. In vitro, RON and MET receptors cross-talk, synergize in intracellular signaling, and cooperate in inducing morphogenic responses. Here we show that the RON and MET oncogenes were expressed in 55% and 56% of human ovarian carcinomas, respectively, and were significantly coexpressed in 42% (P < 0.001). In ovarian carcinoma samples and cell lines we did not find mutations in RON and MET gene kinase domain, nor coexpression of RON and MET receptor ligands (MSP and HGF, respectively). We show that motility and invasiveness of ovarian cancer cells coexpressing MET and RON receptors were elicited by HGF and, to a lesser extent, by MSP. More interestingly, invasion of both reconstituted basement membrane and collagen gel was greatly enhanced by the simultaneous addition of the two ligands. These data suggest that coexpression of the MET and RON receptors confer a selective advantage to ovarian cancer cells and might promote ovarian cancer progression.


Understanding collective agency in bioethics.
Bioethicists tend to focus on the individual as the relevant moral subject. Yet, in highly complex and socially differentiated healthcare systems a number of social groups, each committed to a common cause, are involved in medical decisions and sometimes even try to influence bioethical discourses according to their own agenda. We argue that the significance of these collective actors is unjustifiably neglected in bioethics. The growing influence of collective actors in the fields of biopolitics and bioethics leads us to pursue the question as to how collective moral claims can be characterized and justified. We pay particular attention to elaborating the circumstances under which collective actors can claim 'collective agency.' Specifically, we develop four normative-practical criteria for collective agency in order to determine the conditions that must be given to reasonably speak of 'collective autonomy'. For this purpose, we analyze patient organizations and families, which represent two quite different kinds of groups and can both be conceived as collective actors of high relevance for bioethical practice. Finally, we discuss some practical implications and explain why the existence of a shared practice of trust is of immediate normative relevance in this respect.


Identifying opportunities for cancer prevention during preadolescence and adolescence: puberty as a window of susceptibility.
Early life exposures during times of rapid growth and development are recognized increasingly to impact later life. Epidemiologic studies document an association between exposures at critical windows of susceptibility with outcomes as diverse as childhood and adult obesity, timing of menarche, and risk for hypertension or breast cancer. This article briefly reviews the concept of windows of susceptibility for providers who care for adolescent patients. The theoretical bases for windows of susceptibility is examined, evaluating the relationship between pubertal change and breast cancer as a paradigm, and reviewing the underlying mechanisms, such as epigenetic modification. The long-term sequela of responses to early exposures may impact other adult morbidities; addressing these exposures represents an important challenge for contemporary medicine.


Molecular investigation of Toxocara infection from the serum of people living with HIV in Alborz, Iran.
Toxocara infection is one of the most common neglected infections of poverty and a helminthiasis of global importance. Traditional diagnostic methods such as antibodies detection in serum samples are limited due to cross-reactivity and poor sensitivity. The use of molecular base methods for diagnosis of Toxocara infection in Iran has not been fully explored. The purpose of the current study was to estimate the prevalence of Toxocara infection from serum samples of people living with HIV in Alborz province, Iran using serological and molecular methods. Blood samples were collected from 105 people living with HIV. Epidemiological data of participant were obtained through a structured questionnaire to investigate the risk factors. Patients CD4+ T cell count were recorded. Anti-Toxocara IgG antibodies were detected by ELISA, with a cut-off point of 11. PCR was performed to detect genetic material of Toxocara species in the serum samples. The mean CD4+ count in HIV-infected individuals with positive toxocariasis serology was 255.1 ± 21.6 cells/µL. Seropositivity for Toxocara species was observed in 12/105 (11.4%) people living with HIV. Three samples gave positive results on PCR analysis. Based on the data, a statistically significant relationship was found between anti-Toxocara IgG antibodies seropositivity and underlying conditions (p = 0.017). No significant statistical association was observed between seropositivity for Toxocara and gender, age, exposure to domestic animals or pet keeping, education levels, and occupation (p > 0.05). The findings of PCR confirmed Toxocara DNA in 3/12 (25.0%) serum samples. These findings demonstrated for the first time that people living with HIV from Alborz province, are being exposed to this zoonosis and a relatively high seroprevalence of Toxocara in HIV/AIDS people needs comprehensive health education regarding personal hygiene and how to avoid exposure to this parasite infection, especially in people with an impaired immune system.


A complete species-level molecular phylogeny for the "Eurasian" starlings (Sturnidae: Sturnus, Acridotheres, and allies): recent diversification in a highly social and dispersive avian group.
We generated the first complete phylogeny of extant taxa in a well-defined clade of 26 starling species that is collectively distributed across Eurasia, and which has one species endemic to sub-Saharan Africa. Two species in this group-the European starling Sturnus vulgaris and the common Myna Acridotheres tristis-now occur on continents and islands around the world following human-mediated introductions, and the entire clade is generally notable for being highly social and dispersive, as most of its species breed colonially or move in large flocks as they track ephemeral insect or plant resources, and for associating with humans in urban or agricultural landscapes. Our reconstructions were based on substantial mtDNA (4 kb) and nuclear intron (4 loci, 3 kb total) sequences from 16 species, augmented by mtDNA NDII gene sequences (1 kb) for the remaining 10 taxa for which DNAs were available only from museum skin samples. The resulting mitochondrial gene tree embedded within a multilocus framework shows that the well-studied taxa S. vulgaris/unicolor are the sister lineage to the remaining members of the radiation, from which other relatively early lineages gave rise to forms that are now nomadic or locally migrant in Africa (Creatophora) and western Asia (Pastor). The remaining taxa form a clade with a complicated biogeographic history primarily in central and eastern Asia; this group contains a range of sedentary to highly migratory taxa, as well as widely distributed species and single-island endemics such as the highly endangered Bali myna (Leucopsar). Several groups of species in the genus Acridotheres have low magnitudes of within-group divergence and likely diversified via their respective colonization of islands. The taxonomy of this entire group has remained highly volatile over the past century; we propose dividing these 26 species among 11 reciprocally monophyletic genera (Acridotheres, Poliopsar, Temenuchus, Sturnornis, Leucopsar, Gracupica, Agropsar, Pastor, Creatophora, and Sturnus).


Embolotherapy of a mycotic pseudoaneurysm of the internal mammary artery in chronic granulomatous disease.
We report a case demonstrating an unusual and previously unpublished complication of chronic granulomatous disease (CGD), that is massive hemorrhage from a mycotic pseudoaneurysm of the left internal mammary due to invasive Aspergillus fumigatus of the anterior chest wall. This brief report further illustrates the angiographic diagnosis and embolotherapeutic control of a mycotic pseudoaneurysm of the internal mammary artery.


Fuzzy entropy based on differential evolution for breast gland segmentation.
For the diagnosis and treatment of breast tumors, the automatic detection of glands is a crucial step. The true segmentation of the gland is directly related to effective treatment effect of the patient. Therefore, it is necessary to propose an automatic segmentation algorithm based on mammary gland features. A segmentation method of differential evolution (DE) fuzzy entropy based on mammary gland is proposed in the paper. According to the image fuzzy entropy, the evaluation function of image segmentation is constructed in the first step. Then, the method adopts DE, the image fuzzy entropy parameter is regard as the initial population of individual. After the mutation, crossover and selection of three evolutionary processes to search for the maximum fuzzy entropy of parameters, the optimal threshold of the segmented gland is achieved. Finally, the mammary gland is segmented by the threshold method of maximum fuzzy entropy. Eight breast images with four tissue types are tested 100 times, with accuracy (Acc), sensitivity (Sen), specificity (Spe), positive predictive value (PPV), negative predicted value (NPV), and average structural similarity (Mssim) to measure the segmentation result. The Acc of the proposed algorithm is 98.46 ± 8.02E-03%, 95.93 ± 2.38E-02%, 93.88 ± 6.59E-02%, 94.73 ± 1.82E-01%, 96.19 ± 1.15E-02%, and 97.51 ± 1.36E-02%, 96.64 ± 6.35E-02%, and 94.76 ± 6.21E-02%, respectively. The mean Mssim values of the 100 tests were 0.985, 0.933, 0.924, 0.907, 0.984, 0.928, 0.938, and 0.941, respectively. Our proposed algorithm is more effective and robust in comparison to the other fuzzy entropy based on swarm intelligent optimization algorithms. The experimental results show that the proposed algorithm has higher accuracy in the segmentation of mammary glands, and may serve as a gold standard in the analysis of treatment of breast tumors.


Determination of urinary trans,trans-muconic acid by gas chromatography-mass spectrometry.
A sensitive and specific method for the determination of trans,trans-muconic acid (t,t-MA) in urine is described. After clean-up on an anion-exchange cartridge, t,t-MA was derivatized with BF3-methanol to the dimethyl ester and analyzed by gas chromatography-mass spectrometry (GC-MS), with 2-bromohexanoic acid as an internal standard. The limit of detection was 0.01 mg/l, the coefficient of variation for duplicate analysis in a series of urine samples (n = 50) was 2.6% and the recovery rate ranged from 93.3 to 106.3%. The between-day and within-day precision for the analysis were 7.4 and 14.6%, respectively. The method was applied to the determination of t,t-MA in urine samples from smokers and non-smokers. The mean concentration of t,t-MA in urine of 10 smokers was 0.09 +/- 0.04 mg/g creatinine and was significantly (p = 0.012) higher than that found in urine of 10 non-smokers (0.05 +/- 0.02 mg/g creatinine). In contrast to the results obtained with the commonly used high-performance liquid chromatographic ultraviolet detection (HPLC-UV) methods, no interference between t,t-MA and other urinary compounds was found. This GC-MS method is both specific and sensitive for biomonitoring of low environmental benzene exposure.


Calf muscle arteriovenous malformations detected by technetium-99m erythrocyte venography.
Two cases of calf muscle arteriovenous malformation in young women, presenting clinically as deep venous thrombosis, were initially detected by Tc-99m erythrocyte venography and later confirmed by arteriography. The role of this technique in the investigation of venous thrombosis is discussed, emphasizing the importance of the lateral calf view.


Can consumers learn to ask three questions to improve shared decision making? A feasibility study of the ASK (AskShareKnow) Patient-Clinician Communication Model(®) intervention in a primary health-care setting.
To test the feasibility and assess the uptake and acceptability of implementing a consumer questions programme, AskShareKnow, to encourage consumers to use the questions '1. What are my options; 2. What are the possible benefits and harms of those options; 3. How likely are each of those benefits and harms to happen to me?' These three questions have previously shown important effects in improving the quality of information provided during consultations and in facilitating patient involvement. This single-arm intervention study invited participants attending a reproductive and sexual health-care clinic to view a 4-min video-clip in the waiting room. Participants completed three questionnaires: (T1) prior to viewing the intervention; (T2) immediately after their consultation; and (T3) two weeks later. A total of 121 (78%) participants viewed the video-clip before their consultation. Eighty-four (69%) participants asked one or more questions, and 35 (29%) participants asked all three questions. For those making a decision, 55 (87%) participants asked one or more questions, while 27 (43%) participants asked all three questions. Eighty-seven (72%) participants recommended the questions. After two weeks, 47 (49%) of the participants recalled the questions. Enabling patients to view a short video-clip before an appointment to improve information and involvement in health-care consultations is feasible and led to a high uptake of question asking in consultations. This AskShareKnow programme is a simple and feasible method of training patients to use a brief consumer-targeted intervention that has previously shown important effects in improving the quality of information provided during consultations and in facilitating patient involvement and use of evidence-based questions.


Active-comparator restricted disproportionality analysis for pharmacovigilance signal detection studies of chronic disease medications: An example using sodium/glucose cotransporter 2 inhibitors.
Disproportionality analysis is a common pharmacovigilance tool to detect safety signals of type 2 diabetes medications from spontaneous drug reporting databases. The aim was to demonstrate the impact of using active-comparator restricted disproportionality analysis (ACR-DA), wherein the reference group is restricted to reports with a clinically appropriate active comparator. Using reports from the Food and Drug Administration Adverse Event Reporting System, we assessed if sodium/glucose cotransporter 2 (SGLT2) inhibitors are associated with higher reporting of 5 potential adverse events: acute kidney injury, genitourinary tract infections, diabetic ketoacidosis, fractures, and amputations. For each adverse event, we calculated the proportional reporting ratio (PRR) and adjusted reporting odds ratio (aROR [95% confidence interval, CI]) using 3 types of reference groups: no SGLT2 inhibitor (background risk reference), other diabetes drugs (therapeutic class reference), and dipeptidyl peptidase 4 inhibitors (active comparator reference). Based on ACR-DA, we did not detect a safety signal for acute kidney injury (PRR 0.92 [0.81-1.04]; aROR 0.78 [95% CI 0.72-0.85]) or fractures (PRR 0.44[95% CI 0.17-1.15]; aROR 0.74 [95% CI 0.61-0.91]) associated with SGLT2 inhibitors compared to dipeptidyl peptidase 4 inhibitors. However, we detected safety signals for genitourinary tract infections (PRR 2.75[2.02-3.76]; aROR 2.54[2.26-2.86], diabetic ketoacidosis (PRR 63.85[39.37-103.53; aROR 91.49[70.66-118.48]), and amputations (PRR 52.60 [19.66-140.75]; aROR 22.64 [15.32-33.42]. The use of the proposed ACR-DA to detect safety signals of type 2 diabetes medications may reduce false positive safety signals through careful selection of the comparator which is expected to reduce channelling bias.


Structural basis of the specificity and interaction mechanism of Bmf binding to pro-survival Bcl-2 family proteins.
The apoptotic pathway is regulated by protein-protein interactions between members of the Bcl-2 family. Pro-survival Bcl-2 family proteins act as cell guardians and protect cells against death. Selective binding and neutralization of BH3-only proteins with pro-survival Bcl-2 family proteins is critical for initiating apoptosis. In this study, the binding assay shows that the BH3 peptide derived from the BH3-only protein Bmf has a high affinity for the pro-survival proteins Bcl-2 and Bcl-xL, but a much lower affinity for Mcl-1. The complex structures of Bmf BH3 with Bcl-2, Bcl-xL and Mcl-1 reveal that the α-helical Bmf BH3 accommodates into the canonical groove of these pro-survival proteins, but the conformational changes and some interactions are different among the three complexes. Bmf BH3 forms conserved hydrophobic and salt bridge interactions with Bcl-2 and Bcl-xL, and also establishes several hydrogen bonds to support their binding. However, the highly conserved Asp-Arg salt bridge is not formed in the Mcl-1/Bmf BH3 complex, and few hydrogen bonds are observed. Furthermore, mutational analysis shows that substitutions of less-conserved residues in the α2-α3 region of these pro-survival Bcl-2 family proteins, as well as the highly conserved Arg, lead to significant changes in their binding affinity to Bmf BH3, while substitutions of less-conserved residues in Bmf BH3 have a more dramatic effect on its affinity to Mcl-1. This study provides structural insight into the specificity and interaction mechanism of Bmf BH3 binding to pro-survival Bcl-2 family proteins, and helps guide the design of BH3 mimics targeting pro-survival Bcl-2 family proteins.


Feedback and instructional effects in the voluntary control of digital pulse amplitude.
The effects of verbal instructions and these instructions plus visual analogue feedback on the voluntary control of digital amplitude were examined in 2 groups of 8 subjects over 8 training sessions. Control of pulse amplitude was demonstrated but feedback did not add consistently or reliably to the effect of verbal instructions. Control did not improve over the period of training nor did it become more specific, i.e. the effect did not become localised at the feedback site and pulse interval, respiration rate and forearm muscle activity were implicated in the response throughout. The results are interpreted as providing little support for the theory that learning to control a visceral response is analogous to learning a motor skill.


Projections of upper structure to the spinal cardioacceleratory center in cats: an HRP study using a new microinjection method.
We studied, with the horseradish peroxidase (HRP) method, the supraspinal structure projections to the cardioacceleratory center in the intermediolateral nucleus (ILN) of T3-4 segments of the cat spinal cord. A fiber-filled double-barrel coaxial electrode was devised. The inner barrel electrode, filled with 3 M NaCl solution, was used for stimulating intraspinal structures to determine the cardioacceleratory center. The outer barrel electrode with an Agar stop, filled with a 20% HRP solution, was used for injecting HRP by pulses of positive electric current. In every experiment, HRP was injected into 3 points within the cardioacceleratory center at intervals of 1 mm. Out of 36 experiments, 10 showed that the HRP injection sites were centered in and almost confined to the ILN, and the population of the HRP-labeled cells was not less than 50. Some 1146 HRP-labeled cells were thus identified. They were distributed in the medulla oblongata (72.1%), pons (10.2%), midbrain (8.5%) and hypothalamus (9.2%). They were concentrated in the medullary reticular formation (37.8%), median raphe (26.9%) and pontine reticular formation (10.2%). Contrary to expectation, the HRP-labeled cells were few in the nucleus tractus solitarii (3.7%), paraventricular hypothalamic area (3.3%) and nucleus locus coeruleus (none).


The Dutch Long-Term Care System in Transition: Implications for Municipalities.
The aim of this study is to examine the preparedness of Dutch municipalities (in terms of system readiness for innovation) for the challenges resulting from their new responsibilities under the long-term care reform of January 1, 2015. A qualitative research approach was used by conducting semi-structured interviews with representatives of nine Dutch municipalities responsible for the long-term care of older people in their respective municipalities. Municipalities consider themselves to be largely prepared for their new responsibilities resulting from the long-term care reform. However, this perception mainly applies to practical changes (related to municipalities' organizational preparation for their new responsibilities) occurring in the short-term transition phase, not to the more long-term transformation phase. We argue that municipalities highly underestimate the long-term challenges that lie ahead of them (such as the development of a dedicated 'participation society') and, in fact, seem to fear the uncertainty of the consequences of these challenges.


Regioselectivity and diastereoselectivity of three-component reaction of α-amino acid, dialkyl acetylenedicarboxylates and 2-arylidene-1,3-indanediones.
The 1,3-dipolar cycloaddition of active azomethine ylide, which were generated in situ from addition reaction of α-amino acids with dialkyl acetylenedicarboxylates, with 2-arylidene-1,3-indanediones showed versatile regioselectivity and diastereoselectivity. The reaction of sarcosine and glycine afforded one kind of functionalized spiro[indene-2,3'-pyrrolidines]. The other primary α-amino acids such as alanine, phenylalanine and leucine gave another kind of regioisomeric spiro[indene-2,3'-pyrrolidines]. The cyclic α-amino acids resulted in the corresponding spiro[indene-2,2'-pyrrolizines] and [indene-2,6'-pyrrolo[1,2-c]thiazoles].


Testing Departure from Hardy-Weinberg Proportions.
The Hardy-Weinberg principle, one of the most important principles in population genetics, was originally developed for the study of allele frequency changes in a population over generations. It is now, however, widely used in studies of human diseases to detect inbreeding, population stratification, and genotyping errors. For assessment of deviation from Hardy-Weinberg proportions in data, the most popular approaches include the asymptotic Pearson's chi-squared goodness-of-fit test and the exact test. Pearson's chi-squared goodness-of-fit test is simple and straightforward, but is very sensitive to a small sample size or rare allele frequency. The exact test of Hardy-Weinberg proportions is preferable in these situations. The exact test can be performed through complete enumeration of heterozygote genotypes or on the basis of the Markov chain Monte Carlo procedure. In this chapter, we describe the Hardy-Weinberg principle and the commonly used Hardy-Weinberg proportion tests and their applications, and we demonstrate how the chi-squared test and exact test of Hardy-Weinberg proportions can be performed step-by-step using the popular software programs SAS, R, and PLINK, which have been widely used in genetic association studies, along with numerical examples. We also discuss approaches for testing Hardy-Weinberg proportions in case-control study designs that are better than traditional approaches for testing Hardy-Weinberg proportions in controls only. Finally, we note that deviation from the Hardy-Weinberg proportions in affected individuals can provide evidence for an association between genetic variants and diseases.


The impact of thin idealized media images on body satisfaction: does body appreciation protect women from negative effects?
This article examines whether positive body image can protect women from negative media exposure effects. University women (N=112) were randomly allocated to view advertisements featuring ultra-thin models or control images. Women who reported high levels of body appreciation did not report negative media exposure effects. Furthermore, the protective role of body appreciation was also evident among women known to be vulnerable to media exposure. Women high on thin-ideal internalization and low on body appreciation reported appearance-discrepancies that were more salient and larger when they viewed models compared to the control group. However, women high on thin-ideal internalization and also high on body appreciation rated appearance-discrepancies as less important and no difference in size than the control group. The results support the notion that positive body image protects women from negative environmental appearance messages and suggests that promoting positive body image may be an effective intervention strategy.